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Biomedical subjects

R Cohen

Publications and source records attributed to R Cohen.

At least 127 records · Page 7Linked to original sources
PubMed1999

Ipratropium bromide nasal spray 0.03% and beclomethasone nasal spray alone and in combination for the treatment of rhinorrhea in perennial rhinitis.

BACKGROUND: Perennial rhinitis is a common condition that affects up to 10% to 20% of the population. Multiple agents are frequently administered since no single agent provides complete relief. Studies assessing the benefit/risk of combined therapy are important especially for newly approved agents such as ipratropium bromide nasal spray 0.03%, a topical anticholinergic agent, approved specifically for the treatment of rhinorrhea in allergic and non-allergic perennial rhinitis. OBJECTIVE: To compare the efficacy and safety of the combined use of ipratropium bromide nasal spray 0.03% (42 microg per nostril tid) and beclomethasone dipropionate nasal spray (84 microg per nostril bid) against that of either active agent alone for the treatment of rhinorrhea. DESIGN: Multicenter, 6-week, double-blind, randomized active- and placebo-controlled, parallel trial. SETTING: Allergist and general practitioner clinical practices. PATIENTS: Five hundred thirty-three patients with perennial rhinitis (279 allergic and 274 non-allergic), 8 to 75 years of age, who had at least a mild degree of severity of rhinorrhea for a minimum of 2 hours per day during the 1 week screening period as well as congestion or sneezing also of at least mild severity. INTERVENTION: Either (1) ipratropium bromide nasal spray 0.03% (42 microg per nostril tid) plus beclomethasone dipropionate nasal spray (84 microg per nostril bid), (2) ipratropium bromide nasal spray 0.03% (42 microg per nostril tid) alone, (3) beclomethasone dipropionate nasal spray (84 microg per nostril bid) alone, or (4) vehicle [matching placebo nasal spray for the ipratropium bromide (2 sprays per nostril tid)] or beclomethasone dipropionate (2 sprays per nostril bid). MAIN OUTCOME MEASURE: Severity and duration of rhinorrhea, and patient and physician global assessment of control of rhinorrhea. RESULTS: Ipratropium bromide nasal spray plus beclomethasone nasal spray was more effective than either active agent alone or vehicle in reducing the average severity and duration of rhinorrhea during 4 weeks of treatment. The advantage of ipratropium bromide plus beclomethasone nasal spray was evident by the first day of combined treatment and continued throughout the 2-week treatment period. Ipratropium bromide nasal spray had a faster onset of action during the first week of treatment and reduced the duration of rhinorrhea more than beclomethasone. Beclomethasone nasal spray was more effective in reducing the severity of congestion and sneezing than ipratropium. In patients who had not responded well to a nasal steroid prior to participation in the study based on a questionnaire administered at screening, ipratropium bromide was as effective in the steroid non-responders as steroid responders, whereas beclomethasone was more effective in steroid responders. Combined active therapy was well tolerated with no increase in adverse events over that seen previously with ipratropium bromide or beclomethasone nasal spray alone. CONCLUSIONS: The combined use of ipratropium bromide nasal spray with beclomethasone dipropionate nasal spray is more effective than either active agent for the treatment of rhinorrhea, and does not result in a potentiation of adverse drug reactions. Ipratropium bromide nasal spray 0.03% alone should be considered in patients for whom rhinorrhea is the primary symptom, and its use in combination with a nasal steroid should be considered in patients where rhinorrhea is one of the predominant symptoms, or in patients with rhinorrhea not fully responsive to other therapy.

Administration, Inhalation↗
PubMed1999

Determining working memory from ERP topography.

Event-related potentials were recorded during a delayed matching-to-sample design from 17 volunteers (5 f) using high-resolution (65 channels) EEG-recordings. In the two-stimulus paradigm, the 500-ms stimulus S1 comprised a visual pattern of two diamonds differing in size, angular rotation and location; in the delay period, Working Memory (WM) load was varied in the following way: a stimulus-free interval of 1 s was followed by a 6-s presentation either of a pattern identical to the S1 (low WM load) or of a pattern differing from S1 (high WM load). The 500-ms stimulus S2 comprised one diamond; the subject's task was to indicate by left- or right-hand (respectively) button press, whether the S2 matched the (a) left- or (b) right-positioned S1-diamond, or (c) did not match at all (NoGo). The topographical distribution of activity in the time intervals (a) following S1-offset, (b) during the WM manipulation interval and (c) prior to S2 were evaluated in the signal (scalp potential) and source (Minimum Norm) space. Following S1-offset the ERP pattern was characterised by negativity over posterior areas, slightly more so over the right hemisphere. In the subsequent 6-s interval high WM load elicited a larger negative slow ERP than low WM load, the negativity increase due to high WM load being larger over frontal than central areas. Source modelling indicated activity in anterior areas under high, and posterior activity under low WM load. Asymmetry of activity, although indicating a shift to left-hemispheric activity under high compared to low WM load, varied considerably between subjects. Results suggest that high-resolution ERP recordings allow to examine cortical activity during WM challenge.

Adolescent↗
PubMed1999

Effects of an amino acid dialysate on leucine metabolism in continuous ambulatory peritoneal dialysis patients.

BACKGROUND: Protein-energy malnutrition is frequent in continuous ambulatory peritoneal dialysis (CAPD) patients. The use of amino acids in the dialysate could improve the protein balance, especially if associated to a concomitant energy intake. METHODS: A 1.1% amino acid solution for peritoneal dialysis was administered to CAPD patients over 30 minutes during concomitant absorption of 600 ml water (control study) or of a 600 kcal meal/600 ml. Leucine metabolism was studied using the combination of intravenous [2H3] and intraperitoneal [13C] leucine. RESULTS: The rate of leucine appearance was stimulated by 56 and 53% (control and meal) at 45 minutes. The rates of leucine appearance and disappearance were lower from 180 to 300 minutes during the meal versus control study (P < 0.05). Proteolysis was unaffected during the control study and was inhibited by 25% during the meal study (P < 0.05). During the five-hour cycle dialysis with or without a meal, 80% of the leucine administered into the peritoneum was absorbed. Forty-one percent was retained in the splanchnic bed. Forty-three percent was used for protein synthesis, and 16% was oxidized. CONCLUSIONS: This amino acids solution is efficaciously utilized for protein synthesis in CAPD patients with no effect on protein breakdown. The concomitant ingestion of a carbohydrate-lipid meal inhibits protein breakdown and reinforces a positive effect of the amino acids solution on protein balance.

Adult↗
PubMed1999

A new model for recognizing and rewarding the educational accomplishments of surgery faculty.

Faculty members' educational endeavors have generally not received adequate recognition. The Association for Surgical Education in 1993 established a task force to determine the magnitude of this problem and to create a model to address the challenges and opportunities identified. To obtain baseline information, the task force reviewed information from national sources and the literature on recognizing and rewarding faculty members for educational accomplishments. The group also developed and mailed to surgery departments at all U.S. and Canadian medical schools a questionnaire asking about the educational endeavors of the surgery faculty and their recognition for such activities. The response rate after two mailings was only 56%, but the responses reaffirmed the inadequacy of systems for rewarding and recognizing surgeon-teachers and surgeon-educators, and confirmed that the distinction between the roles of teacher and educator was rarely made. The task force created a four-tier hierarchical model based on the designations teacher, master teacher, educator, and master educator as a framework to offer appropriate recognition and rewards to the faculty, and endorsed a broad definition of educational scholarship. Criteria for various levels of achievement, ways to demonstrate and document educational contributions, appropriate support and recognition, and suggested faculty ranks were defined for these levels. The task force recommended that each surgery department have within its faculty ranks a cadre of trained teachers, a few master teachers, and at least one educator. Departments with a major commitment to education should consider supporting a master educator to serve as a resource not only for the department but also for the department's medical school and other medical schools. Although this model was created for surgery departments, it is generalizable to other disciplines.

Academic Medical Centers↗
PubMed1999

One dose ceftriaxone vs. ten days of amoxicillin/clavulanate therapy for acute otitis media: clinical efficacy and change in nasopharyngeal flora.

OBJECTIVE: To compare the efficacy and the safety of a single intramuscular dose of ceftriaxone, 50 mg/kg, vs. a 10-day course of amoxicillin/clavulanate (amox/clav) therapy, 80 mg/kg/day of amoxicillin: 10 mg/kg/day of clavulanate in three divided doses, in children with acute otitis media (AOM) and to evaluate the changes in nasopharyngeal flora after treatment. METHODS: In a prospective, comparative, open randomized, multicenter trial, children were scheduled to return for visits on Days 12 to 14 (main end point) and Days 28 to 42 after the beginning of treatment for AOM. A nasopharyngeal swab for bacterial culture was obtained before the treatment and at Days 12 to 14. RESULTS: Between February, 1995, and May, 1996, 513 children with a mean age of 14.2 +/- 6.7 months were enrolled. All the patients were evaluable for the safety and intent-to-treat analyses and 463 for the per protocol efficacy. At Days 12 to 14 clinical success was obtained in 186 of the 235 children (79%) given ceftriaxone and in 188 of the 228 children (82.5%) treated with amox/clav. Among the patients with clinical success on Days 12 to 14, the success was maintained at Days 28 to 42 for 108 of 183 (59%) patients in the ceftriaxone group and 103 of 187 (55%) patients in the amox/clav group. Before the antibiotic treatment the percentages of children carrying Streptococcus pneumoniae (59.1%), Haemophilus influenzae (39.4%), Moraxella catarrhalis (55.7%) and the rate of penicillin-resistant S. pneumoniae (52.2%) were comparable between the 2 groups. At Days 12 to 14 the carriage of S. pneumoniae and M. catarrhalis was significantly different between the patients treated with ceftriaxone, 43.9 and 42.2, respectively, and the patients treated with amox/clav, 17.4 and 11.1%, respectively. Among the children carrying S. pneumoniae at Days 12 to 14, the percentage of penicillin-resistant strains reached 63.4% in the ceftriaxone treatment group and 83.0% in the amox/clav treatment group, (P = 0.02). Adverse events (mainly diarrhea) related to the study medication were reported more frequently (P < 0.0001) in the amox/clav treatment group. CONCLUSIONS: In an area with a high rate of penicillin-resistant S. pneumoniae, a single dose of ceftriaxone is as efficient as a 10-day course of amox/clav in the treatment of AOM in young children. There was for the two regimens an increased rate of penicillin-resistant strains among the pneumococci carried, whereas the chance for a child to carry a penicillin resistant S. pneumoniae did not increase after treatment.

Acute Disease↗
PubMed1999

Alteration of the leptin network in late morbid obesity induced in mice by brain infection with canine distemper virus.

Viruses can induce progressive neurologic disorders associated with diverse pathological manifestations, and therefore, viral infection of the brain can impair differentiated neural functions, depending on the initial viral tropism. We have previously reported that canine distemper virus (CDV) targets certain mouse brain structures, including the hypothalamus, early and selectively. Infected mice exhibit acute encephalitis, with late disease, characterized by motor impairment or obesity syndrome, appearing in some of the surviving mice several months after the initial viral replication. In the present study, we show viral persistence in the hypothalami of obese mice, as demonstrated by low, but still significant, levels of CDV nucleoprotein transcripts, associated with a dramatic decrease in F gene mRNAs. Given the pivotal role of the hypothalamus in obesity (eating behavior, energy consumption, and neuroendocrine function) and that of leptin, the adipose tissue-derived satiety factor acting through hypothalamic receptors, we analyzed the leptin networks in both obese and nonobese mice. The discrepancy found between the chronic and dramatic increase in blood leptin levels and the occurrence of obesity may be due to leptin resistance in the brain. In fact, expression of the long leptin receptor isoform, representing the functional leptin receptor, was specifically downregulated in the hypothalami of obese mice, explaining their inability to generate an adequate response to leptin in the brain. Intriguingly, during the acute phase of infection, its expression was increased in CDV-targeted structures in all infected mice and remained high in obese mice in all CDV-targeted structures, except for the hypothalamus. The biphasic change in hypothalamic leptin receptor expression seen during the progression of CDV-induced obesity provides a new paradigm for understanding mechanisms of neuroendocrinological, virus-induced abnormalities.

Animals↗
PubMed1999

Bilateral hemothorax revealing mediastinal parathyroid adenoma.

We report the case of a 63-year-old woman admitted to hospital because of bilateral hemothorax associated with acute respiratory failure and laterotracheal neoformation. A right thoracoscopy biopsy revealed a paratracheal parathyroid adenoma which was responsible for bilateral hemothorax and primary hyperparathyroidism. A curative resection was successfully performed by cervicotomy.

Adenoma↗
PubMed1999

Randomized phase II study of BR96-doxorubicin conjugate in patients with metastatic breast cancer.

PURPOSE: BMS-182248-1 (BR96-doxorubicin immunoconjugate) is a chimeric human/mouse monoclonal antibody linked to approximately eight doxorubicin molecules. The antibody is directed against the Lewis-Y antigen, which is expressed on 75% of all breast cancers but is limited in expression on normal tissues. Preclinical xenograft models demonstrated significant antitumor activity, including cures. A randomized phase II design was chosen to estimate the activity of the BR96-doxorubicin conjugate in metastatic breast cancer in a study population with confirmed sensitivity to single-agent doxorubicin. PATIENTS AND METHODS: Patients with measurable metastatic breast cancer and immunohistochemical evidence of Lewis-Y expression on their tumor received either BR96-doxorubicin conjugate 700 mg/m2 IV over 24 hours or doxorubicin 60 mg/m2 every 3 weeks. Patients were stratified on the basis of prior doxorubicin exposure, visceral disease, and institution. Cross-over to the opposite treatment arm was allowed with progressive or persistently stable disease. RESULTS: Twenty-three patients who had received a median of one prior chemotherapy regimen were assessable. There was one partial response (7%) in 14 patients receiving the BR96-doxorubicin conjugate and one complete response and three partial responses (44%) in nine assessable patients receiving doxorubicin. No patient experienced a clinically significant hypersensitivity reaction. The toxicities were significantly different between the two treatment groups, with the BR96-doxorubicin conjugate group having limited hematologic toxicity, whereas gastrointestinal toxicities, including marked serum amylase and lipase elevations, nausea, and vomiting with gastritis, were prominent. CONCLUSION: The BR96-doxorubicin immunoconjugate has limited clinical antitumor activity in metastatic breast cancer. The gastrointestinal toxicities likely represent binding of the agent to normal tissues expressing the target antigen and may have compromised the delivery of the immunoconjugate to the tumor sites.

Adult↗
PubMed1999

Differential actions of the dopamine agonist bromocriptine on growth of SMtTW tumors exhibiting a prolactin and/or a somatotroph cell phenotype: relation to dopamine D2 receptor expression.

Dopamine (Da) and Da agonists are known to inhibit secretion and proliferation of normal and tumoral PRL cells, through receptors of D2 subtype. Because of the lack of an experimental model, the relationship between bromocriptine (BR) sensitivity and D2 receptor expression is poorly documented. Such a relationship was analyzed using five lineages of spontaneous transplantable rat pituitary tumors (SMtTW) exhibiting different PRL/GH phenotypes. From plasma PRL and GH concentrations of rats bearing the tumors and tumor messenger RNA contents, tumors were classified as PRL (SMtTW2), somatotroph (SMtTW10), or somatomammotroph (SMtTW5) tumors. Two lineages (SMtTW3 and SMtTW4) represented variants producing PRL and GH but with a high predominance of PRL. With the exception of SMtTW4 tumors, which were malignant, all the tumors were benign and differed in their growth rate. Hormone production and growth of tumors with a PRL or a somatomammotroph phenotype were reduced by about 90% under BR treatment, whereas somatotroph tumors and the PRL malignant tumors were totally insensitive to BR. D2 receptor messenger RNA was present in all BR-sensitive tumors and was not detected in BR-resistant tumors. In conclusion, using five lineages of SMtTW tumors that are representative of the most frequent tumors encountered in human pituitary pathology, we found a full concordance between tumor responses to BR and the expression of D2 receptor by the tumors. The identification of a tumor lineage with a malignant phenotype, secreting high amounts of PRL and presenting a resistance to BR, supports the idea that Da-resistant prolactinomas are aggressive tumors.

Animals↗
PubMed1999

Event-related potential correlates of proactive interference in schizophrenic patients and controls.

Performance and event-related potentials (ERPs) were examined in a proactive interference (PI) task with 15 male schizophrenic patients and 15 matched healthy controls. Within a paired-associate task, 30 pairs of semantically unrelated words (A-B) were presented twice, followed by cued recall, in which the paired-associate B had to be named upon cue A. Subsequently, 50% of the A-words were paired with new words (A-C) and presented in random order together with 15 novel pairings (D-E). Slower responses and poorer recall of C- than of E-words in the final recall indicated PI in both groups. During acquisition, the paired-associates (C/E) evoked larger P3 and positive slow wave in controls than in patients. During recall, cues (A/D) evoked a slow wave with predominating anterior negativity in controls and posterior positivity in patients. The group-specific ERP pattern suggests deviant encoding and retrieval processes in schizophrenic individuals.

Adult↗
PubMed1999

A survey of the teaching of undergraduate psychiatry in Israel.

BACKGROUND: The 1960-70s saw significant advances in the teaching of psychiatry in medical schools. Subsequently there have been developments in the structure of health care and in the methods and goals of medical education. METHOD: All four departments of undergraduate teaching of psychiatry in Israel and single departments in Greece, UK and US were asked to respond to a questionnaire about the structure and content of their teaching program. RESULTS: The amount and content of preclinical and clinical teaching have not changed over the last two decades. There has not been a significant "move into the community" and the nucleus of the program, particularly in Israel, is still in-patient psychiatry. None of the departments approached are evaluating clinical skills using performance-based techniques. CONCLUSIONS: The increased awareness of the need for physicians to have knowledge and skills in psychiatry has not lead to an increase in the teaching of psychiatry to medical students. Further, the content of teaching carried out in most of the centers studied does not meet the needs of physicians, particularly those in primary care, who have to identify and manage a wide range of psychopathology.

Education, Medical, Undergraduate↗