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Biomedical subjects

R Cohen

Publications and source records attributed to R Cohen.

At least 253 records · Page 14Linked to original sources
PubMed1994

[Calcitonin gene-related peptide (CGRP)].

Calcitonin gene-related peptide (CGRP), a 37 amino acid peptide resulting from the specific maturation processes of calcitonin gene products, was discovered in 1982. Its messenger RNA was isolated from a calcitonin cancer in rats similar to the human thyroid medullary carcinoma. CGRP is closely related to calcitonin and amylin, and to a lesser extent, to the region coding for the alpha chains of relaxins, insulin and insulin growth factors. In thyroid C cells, calcitonin itself is the major gene product, but CGRP is predominant in the central and peripheral nervous system. CGRP is found in most all tissues and is considered to be a neuromediator of particular importance in the cardiovascular system. CGRP is a powerful endogenous vasodilator in man; plasma concentrations of 56 pmol/l (slightly above physiological levels) provoke flush, hypotension and secondary catecholamine release and subsequent tachycardia. Intravenous injections lead to systemic vasodilatation and redistribution of blood flow to the skin, the brain, and probably the splanchnic territory. It has been suggested that CGRP plays a role in blood pressure modulation in certain pathological conditions. CGRP level is decreased in hypertension and increased in septic shock. In patients with terminal renal failure, CGRP is correlated with excess volaemia. It could affect blood pressure by redistributing blood flow, interacting with the renin-angiotensin system or by inhibiting aldosterone secretion. CGRP may also play a role in modulating cutaneous vascular constriction in Raynaud's syndrome and cerebral vascularization in patients with migraine or meningeal hemorrhage subsequent to rupture of cerebral aneurisms. CGRP increases arterial flow in the cavernous body. Coronarian vascular tone and cardiac performance (positive chronotrope and inotrope effects) are improved. CGRP has also been studied in connection with glucose metabolism and may have other endocrine effects. Finally, CGRP increases electrolyte and water flow in the colon and its bronchoconstrictor effect could be implicated in asthma. The clinical significance of plasma CGRP is not yet known although it may be a marker of poor prognosis in thyroid medullary cancer. Recent studies suggest that CGRP could be a useful therapeutic agent in severe Raynaud syndrome, impotency, ischaemic neurological lesions due to ruptured aneurisms and in severe heart failure.

Amyloid↗
PubMed1994

Smooth-pursuit eye movement dysfunction in schizophrenia: the role of attention and general psychomotor dysfunctions.

Smooth-pursuit eye-tracking performance was examined in 100 schizophrenic patients and various control groups under both attention-enhancing and attention-distracting conditions. The level of attentional demand was varied by introducing a secondary reaction time task that directed attention either toward or away from the visual-tracking target. Distraction from the target led to a significant deterioration of tracking performance in all subjects, which was most pronounced in the group of schizophrenic patients. Attention-enhancement, on the other hand, did not normalize performance in this group. In schizophrenic patients, mainly in the distraction condition, there was a moderate association between performance in tracking and tests presumably measuring prefrontal functions. Tracking accuracy from both conditions was related to general motor performance as measured by the Neurological Evaluation Scale. It was concluded that in schizophrenic patients attentional factors (distraction) may contribute to eye-tracking impairment, and that the impairment may be viewed as an aspect of general motor dysfunctions.

Adolescent↗
PubMed1994

Evaluation of a multicenter ethics objective structured clinical examination.

The purpose of this study was to evaluate a six-station ethics objective structured clinical examination (OSCE) on a volunteer sample of 66 medical students and 33 residents from three Ontario medical schools. The internal consistency reliability was 0.46 and the median interrater reliability was 0.675 (range 0.30 to 0.89). The residents' scores were higher than those of the medical students (F = 2.24, 0.046). Also, the scores differed among the three schools (F = 3.19, p = 0.0004). The ethics OSCE has adequate interrater reliability and construct validity, but low internal consistency reliability. There are differences among the schools that may assist in ethics curriculum evaluation and development.

Brain Death↗
PubMed1994

Reliability and construct validity of a structured technical skills assessment form.

Current methods of evaluating technical competence of surgical residents are subjective and potentially unreliable. This study assesses the reliability and construct validity of a new format for the assessment of technical ability, the two part Structured Technical Skills Assessment Form (STSAF). Part I, which is completed while an operation is proceeding consists of approximately 120 essential components of the procedure. Part II, completed at the end of the operation, is a 10-point global rating form. Forty-one operations were evaluated using the STSAF, with multiple observers present at 26. Inter-rater reliability of both Parts I and II were high (.78 and .73, respectively). Statistically significant differences were noted between senior-resident and junior-resident performances, suggesting construct validity. The incorporation of structured guidelines to the assessment of technical skill leads to high inter-rater reliability and construct validity, which ultimately may result in improved and reproducible evaluations of surgical trainees.

Cholecystectomy↗
PubMed1994

Fixed drug eruption to papaverine.

Papaverine has offered new options for therapy in erectile dysfunction. Various complications have been reported with papaverine, the prominent ones being priapism and liver function abnormalities. We present a previously unreported case of a fixed drug eruption caused by papaverine.

Drug Eruptions↗
PubMed1994

Calcitonin genes (I and II) expression in human nervous and medullary thyroid carcinoma tissues.

The calcitonin gene family comprises two main genes: CALC I which encodes for calcitonin (CT) mRNA in thyroid and calcitonin gene-related peptide I (CGRP I) mRNA in neuronal tissues and CALC II gene which encodes for CGRP II mRNA only. Recently, in normal thyroid and in medullary thyroid carcinoma (MTC), we detected an additional splicing pathway involving the splicing of exon 4 to exon 5 and leading to the expression of a third CALC I mRNA: CT mRNA II. In the present study, we analyzed by polymerase chain reaction the expression of CT mRNAs I and II, CGRP I and II mRNAs in MTC and in human tumors of the nervous system (3 pituitary adenomas, 3 astrocytomas, 2 schwanomas). In pituitary tissues, CGRP II expression was constant and easily detectable in comparison to other tissues. CT mRNA II signal was very low, but clearly detectable after a reamplification indicating that the factors responsible for the splicing of exon 4 to exon 5 are poorly operative in neuronal tissues.

Adenoma↗
PubMed1994

Regulation of heat-shock protein (hsp70) gene expression by hGH and IL2 in rat Nb2 lymphoma cells.

A comparative study of hGH and IL2 post-signaling effects, as examined by RNA expression (Nb29) and protein levels of the heat-shock protein hsp70, was performed in a hormone-dependent rat lymphoma cell line, Nb2-11C. Optimal doses of hGH or IL2 increased Nb29 expression in a dose-dependent manner. Addition of both mitogens to cell cultures affected Nb29 expression and mitogenesis synergystically, indicating a possible interaction between the post-receptoral mechanisms of these mitogens. Pretreatment of the cells with cholera toxin (CT) inhibited Nb29 expression, protein levels and mitogenesis of hGH- or IL2-induced cells up to 50%, indicating the involvement of Gs-proteins in the post-signaling processes of both hGH and IL2. Incubation of cell cultures with low concentrations of pertussis toxin (IAP) (0.01 ng/ml) markedly increased Nb29 expression in hGH but not in IL2-induced cells, suggesting specific involvement of the Gi-protein in post-signaling processes of hGH-induced cells. Addition of the PKC activator 12-O-tetra-decanoyl phorbol ester (TPA) to control cell cultures markedly increased the expression of Nb29 RNA levels but not mitogenesis, indicating that induction of these proteins in the cells is not sufficient for cell proliferation. Furthermore, incubation of hGH- or IL2-induced cells with the potent PKC inhibitor staurosporin (ST) decreased the levels of Nb29 in both hGH- and IL2-induced cells, although the effect of the mitogens differed significantly in their inhibition slopes. These results indicate that activation of PKC is one of the signaling pathways differentially involved in hGH and IL2 stimulation of cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Alkaloids↗
PubMed1994

Event-related and motor responses to probes in a forewarned reaction time task in schizophrenic patients.

Surface-negative brain potentials indicate increased excitability of the underlying cortical neural networks. Consequently, deviant patterns of event-related potentials in schizophrenic patients reveal an atypical regulation of cortical excitability. Twelve patients with a chronic schizophrenic disorder and 12 matched control subjects were investigated using a probe paradigm: A contingent negative variation (CNV) was evoked in a forewarned reaction time paradigm. Clicks were presented before, during and after elicitation of the CNV. Click-evoked responses allow one to 'probe' the current brain state, particularly neuronal excitability, which is also reflected by the slow potentials. During the measurements, subjects pressed one button in response to the offset of the visual warning stimulus and a different button in response to the acoustic probes, the latter button press being a behavioral indication of the brain's excitability. In the forewarned reaction time task, patients developed a CNV with a frontal maximum, while the CNV in control subjects was predominantly centro-parietal. This atypical topographical pattern of the CNV may indicate a different spatio-temporal regulation of cortical preparatory processes in schizophrenics. Motor responses were accelerated during negative potential shifts in both patients and controls, with responses being slower overall in patients. In patients, probe-evoked potentials revealed a smaller N100, but a larger P300, than in controls. The covariation of these brain waves with slow potentials, however, turned out to be similar for both groups.

Adult↗
PubMed1994

[Strategy of exploration of states of growth hormone hypersecretion].

GH secretion is épisodic in humans. Isolated plasma concentrations thus cannot be used to diagnose excess secretion. Assays on GH secretion require repeat determinations of plasma levels over extended 24 h periods. In so-called conjunctive GH hypersecretion conditions (denutrition, critical states), excessive GH secretion is associated with resistance to this hormone, as indicated by a decrease in plasma IGF-1 concentrations. In contrast, IGF-1 concentrations are high and correlated with GH levels during permanent GH hypersecretion that occurs in acromegaly. Testing for this disorder will vary according to the clinician's objectives.

Acromegaly↗
PubMed1994

'Oncocheck': an international external quality assessment scheme for immunoassays of tumor markers.

Starting from November 1990, an international External Quality Assessment Scheme (EQAS) for immmunoassays of tumor markers has been organized. Presently, 238 laboratories from France, Germany, Italy, Japan and Spain participate in the scheme. In this report the main features of the EQAS and data processing are outlined. Results collected during the 1992-cycle allow evaluation of the state of the art of AFP, CEA, CA 19-9, CA 15-3, CA 125 and PSA immunoassays. According to their analytical performances, the 6 tumor marker immunoassays can be classified into several groups, the first including AFP and CA 15-3 for which both total variability and within-kit agreement are good. For CEA assay, performance can be considered as satisfactory even though further improvements of between-lab agreement would be welcome. For the 3 other tumor markers, the higher total variability indicates an urgent need for a better standardization by improvement of either both within-kit and between-kit agreements (CA 19-9) or between-kit agreement mainly (PSA, CA 125).

Biomarkers, Tumor↗
PubMed1994

Detection by DNA fingerprinting of somatic changes during the establishment of a new prostate cell line.

The establishment of a new prostate cell line (BM1604) from a human prostatic adenocarcinoma is reported. The line was rapidly established by culture of tissue on an extracellular matrix, previously laid down by culture of non-related cells. The method has been shown to work well, and other prostate lines have recently been cultured in this way. The cells have a doubling time of 28 h. DNA fingerprinting comparison of the genome from the tumour, the germline and the cells shows that somatic mutations have occurred in the tumour and that clonal selection has clearly occurred in establishment of the line. Many somatic mutations are apparent in the selected cells, which are now stable in culture. This method and the cells may be a useful addition to the limited material available for the in vitro study of prostate cells.

Adenocarcinoma↗
PubMed1994

Preschoolers' evaluations of physical disabilities: a consideration of attitudes and behavior.

Assessed preschoolers' attitudes about orthopedically handicapped individuals with a standard picture-ranking task. Children generally exhibited a functionally related preference for nonhandicapped individuals. One month later, the same children were videotaped reading and playing basketball with a female adult in a wheelchair or in a chair. Preferences for a normal play partner during reading or during sports on the picture-ranking task did not relate to frequency of social interactions. Liking preference for a normal play partner, in conjunction with gender of the child, predicted frequency of social interactions during both tasks regardless of examiner's handicap status. Thus, the adoption of a negative bias had a general influence; any potential behavioral biases, as reflective of preference biases, were undifferentiated and unfocused in these preschoolers.

Attitude to Health↗
PubMed1994

Refinements in the methodology of injection for transvaginal gamete intra-fallopian transfer.

Eighty-seven volunteer patients with non-tubal infertility initially intending to undergo gamete intra-Fallopian tube transfer (GIFT) via a transabdominal route were re-scheduled for ultrasound-guided transvaginal GIFT which was performed using a Jansen-Anderson tubal transfer set. Emphasis was placed on (i) definite ultrasound confirmation of the transfer catheter within the Fallopian tube, (ii) low transfer volumes (50 microliters), (iii) high sperm transfer densities and (iv) slow injection of gametes. Transvaginal Fallopian tube catheterization was possible in 83 patients (95.4%). Twenty-three of 83 (27.7%) patients conceived (clinical pregnancy). The viable ongoing pregnancy rate was 20.5%. These results compare favourably to those previously reported for both transvaginal and transabdominal GIFT. This study suggested that the fluid dynamics of gamete injection following transvaginal Fallopian tube catheterization are different to those following transabdominal methods. Further study is necessary to define the optimal methodology for transvaginal GIFT and to enhance the ability of the procedure to produce pregnancy rates comparable to transabdominal GIFT.

Adult↗
PubMed1994

Students' time allocation in a required third-year ambulatory care clerkship.

PURPOSE: To assess time use by students during clinic sessions of an ambulatory care clerkship. METHOD: All 207 third-year students at the Medical College of Wisconsin during 1991-92 were asked to report their time use in eight categories during two clinic sessions of the three-week clinical component of the required clerkship in ambulatory care medicine. Other variables assessed were site of clinical rotation, first versus third week of rotation, and time of year of rotation. The statistical methods used were t-tests and one-way analysis of variance. RESULTS: Of the 207 students, 192 (93%) completed time-allocation reports for the first and third weeks of their rotations. The average time spent per clinic session was four hours. Compared with the students at faculty practice sites, the students at private practice sites spent significantly more time observing and working with preceptors as they saw patients and significantly less time doing solo clinical work (reviewing and writing in charts). During the course of each rotation, the students increased the time they saw patients by themselves and decreased the time they observed preceptors. As the year progressed, later cohorts of students spent less time observing preceptors and more time working by themselves. CONCLUSION: Both within and across rotations, the students eventually spent less time observing and more time working independently. However, the results suggest that preceptors in private practice may not allow students as much autonomy as do faculty preceptors. Further research is needed to determine (1) whether the differences between types of preceptors result in meaningful differences in the quality of education and (2) which activities or mixes of activities contribute most to students' education.

Ambulatory Care↗
PubMed1994

A comparative analysis of the costs of administration of an OSCE (objective structured clinical examination).

BACKGROUND: The objective structured clinical examination (OSCE) has become an accepted technique for the evaluation of clinical competence in medicine. Although advances have been made in our knowledge of the psychometric aspects of the OSCE, extremely little has been written about feasibility and cost issues. Given the current economic imperative to control costs and the extremely scant literature on the costs of developing and administering an examination in medicine, the authors felt it timely and relevant to explore issues related to the cost of the OSCE. METHOD: In 1991-92 and in 1992-93, costs and time requirements to implement and administer a structured oral (SO) examination and a six-station OSCE for a surgical clerkship at the University of Toronto Faculty of Medicine were gathered by review of invoices, interviews with those involved, and perusal of diaries kept by staff. RESULTS: To develop and administer the six-station OSCE, 327.5 hours of staff and faculty time were required for each rotation of surgical clerks (8.2 hours per student). The SO examination required 110 hours of staff and faculty time (2.75 hours per student). Direct expenses for the OSCE amounted to U.S. $6.90 per student per station, compared with no direct expense for the SO examination. CONCLUSION: The OSCE was more time-consuming and more expensive in human and material costs than the SO examination. However, costs of the OSCE can be substantially reduced from approximately U.S. $35 to U.S. ! per student per station if test developers, standardized patients, support staff, and examiners can donate their time. The authors compare the costs and time requirements of their OSCE with those of other OSCEs reported in the literature, and they provide guidelines to assist educators in deciding whether the costs of an OSCE are justifiable in the educators' individual settings.

Clinical Clerkship↗
PubMed1994

Bilateral adrenal hemorrhage and adrenal insufficiency in a patient with lymphomatous adrenal infiltration following administration of a fusion toxin (DAB486 interleukin-2).

DAB486IL-2 is a novel fusion toxin in which the ADP-ribosyltransferase and membrane-translocating domains of diphtheria toxin have been combined with the interleukin-2 (IL-2) gene, creating a recombinant protein capable of selectively intoxicating cells bearing the high-affinity IL-2 receptor. Clinical activity has been documented in Hodgkin disease and the non-Hodgkin lymphomas; toxicities have been minimal and include mild hepatic transaminitis, proteinuria, and hypersensitivity reactions. In this report, a patient with tumor-stage cutaneous T-cell lymphoma developed clinical adrenal failure with bilateral adrenal hemorrhage and necrosis 7 weeks after completing a 5-day course of treatment with DAB486IL-2. The relationship of fusion toxin therapy to the development of this unusual toxicity is discussed.

Adrenal Gland Diseases↗
PubMed1994

In vitro killing activities of antibiotics at clinically achievable concentrations in cerebrospinal fluid against penicillin-resistant Streptococcus pneumoniae isolated from children with meningitis.

We evaluated the in vitro killing activities of ceftriaxone, imipenem, vancomycin, gentamicin, fosfomycin, and rifampin, alone and in combination, against 26 Streptococcus pneumoniae strains (penicillin G MICs, > 0.125 to 2 micrograms/ml) isolated from the cerebrospinal fluid of children with meningitis. The antibiotics were tested at clinically achievable concentrations in cerebrospinal fluid. After 5 h of incubation, imipenem was the most effective drug. None of the combinations had synergistic activity. Killing by beta-lactam antibiotics or vancomycin was enhanced by the addition of gentamicin, reduced by the addition of rifampin, and unaffected by the addition of fosfomycin.

Anti-Bacterial Agents↗