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Biomedical subjects

D Cohen

Publications and source records attributed to D Cohen.

At least 235 records · Page 13Linked to original sources
PubMed1997

Search for DNA sequence variations using a MutS-based technology.

The search for DNA sequence variations (DSV) is emphasized with genetic studies of a large number of multifactorial diseases. Saturation of regions of interest with diallelic polymorphisms will be an essential step to pinpoint, through association studies, predisposing genes. We have developed a solid-phase method based on the ability of mismatch binding protein MutS to recognize single nucleotide mismatches. This approach was applied to the study of 83 sequence-tagged sites (STSs) extracted from an eight centimorgans (cM) chromosome 21 region. One-third of tested STSs were found to be polymorphic leading to a frequency of one DSV every 822 base pairs (bp). Sequencing of analyzed STSs showed the high reliability of the MutS-based technology for mismatches up to 2 bp in DNA fragments ranging in size from 200 bp to 1 kilobase (kb). The entire assay which is performed in a solid-phase format without the need of electrophoresis or sequencing, will provide an efficient tool for new polymorphism detection.

Adenosine Triphosphatases↗
PubMed1997

An outbreak of Trichinella spiralis infection in southern Lebanon.

An outbreak of trichinosis occurred during January 1995 in a south Lebanese village with a population of 800-1000 persons. The estimated number of persons treated for a Trichinella-like illness was 200. Sixty-three persons sought medical attention at a local infirmary: 44 of them were diagnosed as having trichinosis or suspected trichinosis according to their clinical symptoms, signs and laboratory tests. An environmental investigation indicated that the source of infection was pork obtained from a single butcher in the village and consumed uncooked, as an ingredient of 'kubeniye' (a local dish), during Christmas and New Year's meals. Sera of patients, suspected patients, and asymptomatic controls were tested for the presence of anti-Trichinella antibodies. Eight (89%) of the 9 tested patients were positive, 1 (11%) was negative. Among the 7 suspected patients, 2 (28.5%) were positive, 3 (42.9%) had equivocal results, and 2 (28.5%) were negative. Among the 20 asymptomatic persons, 3 (15%) were positive, 12 (60%) negative and 5 (25%) had equivocal results. Specimens from the implicated pork meat were examined by microscopy and were found to contain encysted larvae of Trichinella spiralis. This outbreak of trichinosis is one of the largest reported. Previous outbreaks in Lebanon occurred under very similar circumstances, indicating a need to control and prevent the trading of pork meat that is not under veterinary control, and to increase the awareness of the population for this problem.

Adult↗
PubMed1997

Thresholds and tolerance of physical pain in suicidal and nonsuicidal adolescents.

It was hypothesized that suicidal inpatient adolescents (n = 38) will exhibit a higher tolerance for physical pain than nonsuicidal inpatients (n = 29) and control participants (n = 34). Participants provided self-reports of hopelessness, dissociation, suicidal tendencies, depression, and anxiety and were administered a series of thermal pain stimuli by means of a Thermal Sensory Analyzer (TSA). The suicidal participants significantly differed from the 2 controls in pain thresholds and tolerance and in most self-report measures, even after controlling for motivation, medication, diagnosis, and length of hospitalization. Significant correlations were found between pain measures and self-report measures. The results were discussed in terms of the role that body experiences play in suicidal behavior.

Adolescent↗
PubMed1997

Interaction of cyclosporin derivatives with the ATPase activity of human P-glycoprotein.

1. P-glycoprotein, a 170-180 kDa membrane glycoprotein that mediates multidrug resistance, hydrolyses ATP to efflux a broad spectrum of hydrophobic agents. In this study, we analysed the effects of three MDR reversing agents, verapamil, cyclosporin A and [3'-keto-Bmt1]-[Val2]-cyclosporin (PSC 833), on the adenosine triphosphatase (ATPase) activity of human P-glycoprotein. 2. P-glycoprotein was immunoprecipitated with a monoclonal antibody (MRK-16) and the P-glycoprotein-MRK-16-Protein A-Sepharose complexes obtained were subjected to a coupled enzyme ATPase assay. 3. While verapamil activated the ATPase, the cyclosporin derivatives inhibited both the substrate-stimulated and the basal P-glycoprotein ATPase. No significant difference was observed between PSC 833 and cyclosporin A on the inhibition of basal P-glycoprotein ATPase activity. PSC 833 was more potent than cyclosporin A for the substrate-stimulated activity. 4. Kinetic analysis indicated a competitive inhibition of verapamil-stimulated ATPase by PSC 833. 5. The binding of 8-azido-[alpha-32P]-ATP to P-glycoprotein was not altered by the cyclosporin derivatives, verapamil, vinblastine and doxorubicin, suggesting that the modulation by these agents of P-glycoprotein ATPase cannot be attributed to an effect on ATP binding to P-glycoprotein. 6. The interaction of the cyclosporin derivatives with ATPase of P-glycoprotein might present an alternative and/or additional mechanism of action for the modulation of P-glycoprotein function.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1997

Characterization and quantitative analysis of serum IgG class and subclass response to Shigella sonnei and Shigella flexneri 2a lipopolysaccharide following natural Shigella infection.

The IgG subclass response to Shigella sonnei and Shigella flexneri 2a lipopolysaccharide (LPS) was examined in subjects naturally exposed to these organisms. Affinity-purified LPS antibodies obtained using a column of Shigella LPS bound to epoxy-activated Sepharose 6B were used as standards to calibrate the serum antibody response to natural Shigella infection. The geometric mean concentrations of specific IgG in sera from those not exposed to Shigella organisms were 7.9 microg/mL against S. sonnei LPS and 18.6 microg/mL against S. flexneri 2a LPS. After natural exposure to S. sonnei or S. flexneri 2a, the concentrations rose to 30.3 and 127.9 microg/mL, respectively. IgG2 was the major component in the anti-S. flexneri subclass response, while the anti-S. sonnei response was dominated by IgG1. High levels of IgG1 antibodies before exposure to organisms from either Shigella serogroup correlated with a lower risk of developing symptomatic infection.

Adolescent↗
PubMed1997

Insights into the increased oxygen demand during chest physiotherapy.

OBJECTIVES: To determine the mechanism responsible for the increase in oxygen consumption (VO2) during chest physical therapy. Specifically, to examine the hypothesis that muscular activity is the major contributor to the increase in oxygen demand. DESIGN: Prospective, observational study. SETTING: University hospital surgical intensive care unit. PATIENTS: Phase one included 13 patients who were mechanically ventilated after coronary artery bypass surgery. Phase two involved seven mechanically ventilated patients who had undergone major vascular or abdominal surgery. INTERVENTIONS: Phase one involved turning patients to the lateral decubitus position. During the second phase, patients were given midazolam (0.15 microg/kg) 2 mins before an initial chest physiotherapy session and midazolam plus vecuronium (0.7 mg/kg) before a subsequent session. Physiologic measurements were made during the resting periods before and following each session, as well as at the completion of the intervention. MEASUREMENTS AND MAIN RESULTS: Turning patients to the lateral position resulted in significant increases in oxygen uptake and CO2 elimination (VCO2). VO2 increased from 219 +/- 21 (SD) mL/min at rest to 324 +/- 58 mL/min (p <.05) with turning. These increases in oxygen demand were met by increases in both oxygen delivery (852 +/- 238 mL/min at rest to 1116 +/- 430 mL/min, p < .05) and extraction (0.27 +/- 0.7 at rest to 0.32 +/- 0.09, p < .05). There were associated increases in hemodynamic and respiratory variables including heart rate and systolic blood pressure. The administration of vecuronium completely suppressed the 50% increases in VO2 and VCO2 seen without the use of a muscle relaxant. The increases in systolic blood pressure were unaffected by vecuronium. The magnitude of the increase in PaCO2 (32 +/- 5 torr [4.3 +/- 0.7 kPa] at rest to 36 +/- 5 torr [4.8 +/- 0.7 kPa] during therapy, p < .05), was not accentuated by vecuronium (30 +/- 4 torr [4.0 +/- 0.5 kPa] to 35 +/- 6 torr [4.7 +/- 0.8 kPa], p < .05) despite a lack of any increase in minute ventilation or respiratory rate. This change was due to the parallel suppression of VCO2. CONCLUSIONS: The increase in metabolic demand during chest physiotherapy is the result of increased muscular activity as evidenced by the suppression of VO2 following the administration of the muscle relaxant and the observation that turning a patient into the lateral decubitus position produces similar increases in VO2. The increases in blood pressure and cardiac output are due to another mechanism, most likely enhanced sympathetic output. The increase in physiologic activity produced by chest physiotherapy is thus secondary to both exercise-like and stress-like responses.

Aged↗
PubMed1997

Dyspareunia: sexual dysfunction or pain syndrome?

This study investigated the clinical attributes of dyspareunia and the variables used to classify it. A systematic clinical description of the pain symptomatology was obtained through the administration of a structured interview and standardized pain measures to 112 women suffering from dyspareunia, ranging in age from 19 to 65. Subjects also underwent three different gynecological examinations and completed standardized measures of psychopathology, marital adjustment, and sexual attitudes, the results of which were used to test the ability of three different classification systems, including the DSM-IV, to predict physical and psychosocial outcomes. Using classification analysis, temporal pattern and location of the pain were found to be the best predictors of physical diagnoses, although none of the taxa in the three classification systems tested were related to psychosocial outcomes. Sexual impairment of women suffering from dyspareunia notwithstanding, the results support the consideration of dyspareunia as primarily a pain syndrome, rather than a sexual dysfunction.

Adaptation, Psychological↗
PubMed1997

Eosinophilic granuloma of the clivus: case report, follow-up of two previously reported cases, and review of the literature on cranial base eosinophilic granuloma.

OBJECTIVE AND IMPORTANCE: To our knowledge, this is the first reported case of the use of stereotactic radiotherapy for an eosinophilic granuloma (EG) of the clivus. We report follow-up information on two previously reported cases and suggest a management plan for this rare lesion. CLINICAL PRESENTATION: We report the case of a 4.5-year-old boy who presented with a complete abducens palsy on the right with an associated head turn. A computed tomographic scan of his head revealed a lytic lesion on that side, and magnetic resonance imaging showed the mass to be of low intensity on T1-weighted images and of high intensity on T2-weighted images with heterogeneous enhancement. INTERVENTION: A transnasal stereotactic biopsy was performed, revealing an EG. The patient was treated with stereotactic radiotherapy, and he became symptom-free with radiographic resolution of his lesion. Reviewing the literature, we found 13 series with 87 cases of EG in the petrous portion of the temporal bone. EG in the cranial base occurring outside of the temporal bone or in the temporal bone and extending intracranially is, however, quite rare, with only nine other cases reported, two of them clival. CONCLUSION: These findings suggest a classification schema in which cranial base EG lesions be grouped with either the more common extracranial petrous temporal bone lesions or the very rare intracranial lesions. Although there are few cases in the literature, treatment results indicate that clival EG, and perhaps all intracranial cranial base EGs, be treated by a biopsy alone, followed by surgery or stereotactic radiotherapy if there is an incomplete resolution of the symptoms or if there is a recurrence.

Child, Preschool↗
PubMed1997

Moderately high consumption of ethanol suppresses bone resorption in ovariectomized but not in sexually intact adult female rats.

Epidemiological studies suggest that moderate consumption of alcoholic beverages may be beneficial for bone in postmenopausal women. To investigate prospectively these uncontrolled observations, female rats were divided in four groups of 10 animals each and treated with 1) ovariectomy (OVX) and 2.5% ethanol diet (OVX-ETOH group), 2) OVX and control diet (OVX-C group), 3) sham surgery and 2.5% ethanol diet (SHAM-ETOH group), or 3) sham surgery and control diet (SHAM-C group). Three weeks after surgery, bone histomorphometry revealed that the OVX-C group, as expected, had lower trabecular bone volume and higher parameters of bone formation and resorption than the SHAM-C group (p < 0.01). Intake of ethanol did not change these parameters in the SHAM rats, but in the OVX rats it was associated with sharp reduction in parameters of bone resorption (p < 0.01) without a concomitant effect on parameters of bone formation. The cytokines are believed to contribute to accelerated bone resorption during the early postmenopausal period. Indeed, the peripheral blood monocytic cells (PBMC) from the OVX-C rats produced higher amounts of TNF-alpha than the PBMC from the SHAM-C rats (p < 0.05) and administration of ethanol prevented this increase in OVX rats but had no effect in SHAM rats. In summary, short-term intake of moderate doses of ethanol was associated with markedly different effects in rats with and without ovarian function. Although ethanol had no significant effect on the bone tissue and TNF-alpha production of the SHAM rats, it was associated with markedly lower parameters of bone resorption and less TNF-alpha production in the OVX animals. This suggests that exposure to low-dose ethanol may protect from osteopenia following cessation of ovarian function.

Adult↗
PubMed1997

Cotard's syndrome in a 15-year-old girl.

We here describe a case of Cotard's syndrome in a 15-year-old girl who exhibited a short period of malignant catatonia, and the positive effect of electroconvulsive therapy (ECT) on her disorder. A psychopathological hypothesis is proposed.

Adolescent↗
PubMed1997

Involvement of the transcription factor NF-IL6 in phorbol ester induction of P-glycoprotein in U937 cells.

Previously, we showed that the nuclear factor NF-IL6 binds and trans-activates the promoter of the human multidrug resistance gene (MDR1) encoding P-glycoprotein (N. J. Combates et al., J. Biol. Chem., 269: 29715-29719, 1994). In this study, we investigated the physiological relevance of MDR1 gene regulation by NF-IL6 in response to PMA (phorbol 12-myristate 13-acetate)-induced differentiation. Treatment of U937 cells, a human promonocytic cell line, with PMA induced their differentiation along the macrophage/monocytic cell lineage. The cellular changes were found to be accompanied by an increase in P-glycoprotein expression at the cell surface. PMA treatment of U937 cells also resulted in the synthesis of the three forms of NF-IL6 and an enhanced DNA binding activity of nuclear extracts to a probe derived from the MDR1 promoter. The majority of the DNA-protein complex could be supershifted by an NF-IL6 reactive antibody but not by antibodies for CAAT/enhancer binding protein alpha and delta, c-fos, or c-jun. Furthermore, transient transfection studies demonstrated that PMA enhanced the activity of a MDR1 promoter-driven luciferase gene construct to a greater extent as compared with the activity of a reporter construct containing mutations within the NF-IL6 responsive element. These results indicate a correlation between NF-IL6 gene expression and the regulation of the MDR1 gene. Furthermore, these observations also suggest that P-glycoprotein expression is part of the macrophage differentiation process.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1997

The impact of nonacademic variables on performance at two medical schools.

Recent research shows that nonacademic variables must be taken into account when analyzing the indicators of medical student success. However, most previous studies have been limited to a single institution or population. This study investigated the relationship between nonacademic variables and performance at two very different medical schools. The Noncognitive Questionnaire was administered to 104 students at School A (predominantly white and historically oriented toward women) and 102 at School B (predominantly black). Correlation and multiple regression analyses were conducted to determine the relationship among nonacademic variables, undergraduate academic variables (Medical College Admission Test, undergraduate grade point average, and college quality), basic science grades, and US Medical Licensure Exam Step I (USMLE 1) scores. At School A, leadership/decisiveness, expected difficulty, and motivation predicted higher USMLE I scores and higher basic science grades each semester. At School B, expected difficulty was correlated with higher first semester grades only. For School A women, initiative/commitment was positively associated with both higher grades and higher USMLE scores. For black students of School B, expected difficulty was positively associated with higher grades. Identifying school-specific nonacademic variables of performance is critical to developing improved student support services.

Achievement↗
PubMed1997

Intravesical morphine analgesia after bladder surgery.

PURPOSE: A recent demonstration of peripheral opioid receptors suggested the possibility of delivering morphine locally into the bladder after reimplantation for ameliorating the discomfort of postoperative bladder irritation with spasms. Since we do not use bladder drainage after reimplantation, dripping a morphine solution into the bladder permits contact with the urothelium between voidings. A pilot trial using an arbitrary concentration was subjectively beneficial for treating these patients postoperatively. We now report a prospective randomized study evaluating the effectiveness and dosage of various concentrations of intravesical morphine infusions. MATERIALS AND METHODS: A total of 52 children undergoing ureteral reimplantation was randomized to receive 1 of 3 concentrations of intravesical morphine (0.05, 0.375 or 0.5 mg./ml.). A small feeding tube remained in the bladder to drip a continuous infusion postoperatively. Subsequent postoperative pain was treated with meperidine, acetaminophen and codeine, and/or a belladonna and opium suppository. During each shift a nurse assisted the child in assessing pain using a Baker-Wong faces scale. Bladder infusion was discontinued after day 3 postoperatively and plasma morphine levels were measured on the first morning postoperatively. Kruskal-Wallis and paired t tests were used to evaluate significance. RESULTS: Patients reported greater pain in the group infused with 0.05 mg./ml. on 4 of 6 shifts on the first 2 days postoperatively. No difference was noted on postoperative day 3. Plasma morphine was undetectable by high pressure liquid chromatography. CONCLUSIONS: This study offers objective evidence that bladder morphine infusion is effective for ameliorating postoperative pain in the first 48 hours after intravesical ureteral reimplantation. The dose given today is 0.5 mg./ml. delivered at 0.04 ml./kg. per hour.

Administration, Intravesical↗
PubMed1997

Use of electroconvulsive therapy in adolescents.

Electroconvulsive therapy (ECT) is used in adolescent psychiatric practice, yet few studies have been conducted to assess its use for 13-19-year-olds. Efficacy, indications, side effects, technical characteristics, and outcome are uncertain. We retrospectively reviewed the medical records of 21 adolescents treated with bilateral ECT in our department from 1984 through 1995. In our series, ECT was effective in treating both maniac and depressive episodes, with a high rate of relapse at 1 year follow-up (approximately 40%). Clinical improvement was only partial and in schizophrenia and schizoaffective episodes. Seizure threshold was associated with gender, but not with the cumulative number of treatments. Adverse effects were frequent, but were usually transient with only moderate discomfort, even in patients with concomitant medical problems. We conclude that ECT is a safe and effective treatment for adolescents with severe and intractable mental illness, and it has the same indications and effects as in adults.

Adolescent↗
PubMed1997

[Prescription of stimulants for hyperactive children: a pilot study of incentives and constraints on parents, teachers and physicians].

The scientific consensus on the use of stimulants to treat "hyperactive" or ADHD-diagnosed children amounts to recognizing a calming effect on children's disruptive behavior and better performance of repetitive tasks, both in the short-term. Long-term effects remain unknown. Still, in Québec, prescription of stimulants to children of welfare recipients nearly tripled between 1990 and 1994, reaching a prevalence of 11.9%. Using a systemic model integrating three approaches (medicalization of deviance, political economy, and strategic analysis), we conceptualized the decision to prescribe as the result of interactions involving different actors holding unequal power and seeking to further their interests. We attempted to establish the defendability of this model by means of in-depth interviews with five parents, four primary school teachers and three physicians in prolonged contact with a hyperactive child receiving stimulant medication. Data from the interviews reveal the omnipresence of the medical model in the hyperactivity treatment system, although teachers rather than physicians appear as the engine of this medicalization. According to parents and physicians, teachers identify and "diagnose" children, propose the use of medication to parents and, in some cases, the school requires that doctors write a prescription. Doctors admit that medical evaluation of referred children is often inadequate. For their part, teachers stress the growing difficulties of their task and the lack of psychosocial supports in the schools. Our respondents' comments highlight the divergent interests of the actors involved as well as each actor's own perception that he or she wishes to act differently but lacks any real choice other than opting for medication. These limited observations should be validated in further studies. They suggest that the current system functions irrationally and that we should not expect it to act in the best interests of children.

Attention Deficit Disorder with Hyperactivity↗