Distribution of 5-hydroxytryptamine-immunoreactive boutons on immunohistochemically-identified Renshaw cells in cat and rat lumbar spinal cord

A combination of anti-gephyrin- and anti-calbindin D28k-immunoreactivity was used to identify 129 and 171 Renshaw cells and their dendrites in cat and rat lumbar spinal cord, respectively. Using anti-5-hydroxytryptamine-immunoreactivity to label serotoninergic fibers and boutons, 1048 serotoninergic boutons were observed in close contact with the immunolabeled Renshaw cells, with an average of 4.4 and 2.8 close contacts on cat and rat Renshaw cells, respectively. Two-thirds of the observed appositions were formed on the somatic membrane.     

Designing an intervention to prevent suicide: PROSPECT (Prevention of Suicide in Primary Care Elderly: Collaborative Trial)

Suicide is a major public health problem with greatest risk in the very old. This paper describes an approach to reducing the risk of suicide by intervening on depression in elderly primary care patients. Depression is an appropriate target for an intervention as it is highly prevalent in primary care, is a strong risk factor for suicide, and is more often than not inadequately treated. PROSPECT (Prevention of Suicide in Primary Care Elderly: Collaborative Trial) is a National institute of Mental Health (NIMH)-funded collaborative study that is testing this approach to suicide risk prevention in 18 primary care practices in the United States. PROSPECT'S intervention of "guideline management" introduces a health specialist into the primary care setting to help physicians provide "on-time, on-target" treatment and long-term management of late-life depression following structured clinical guidelines. The effectiveness of the intervention in reducing suicidal risk and depression is evaluated by following a representative sample of older patients identified using a 2-stage design.     

The dorzolamide/timolol combination versus timolol plus pilocarpine: patient preference and impact on daily life. United States Patient Preference Study Group. International Patient Preference Study Group.

PURPOSE: To compare the 2.0% dorzolamide/0.5% timolol fixed combination (COSOPT; Merck & Co., Whitehouse Station, NJ) to 0.5% timolol plus 2.0% pilocarpine given concomitantly, and to determine patient preference, tolerability, and impact on daily life in patients with elevated intraocular pressure (IOP). METHODS: Two multi-center, randomized, cross-over, observer masked studies were conducted, one in the United States (97 patients) and one in Europe (93 patients). The Comparison of Ophthalmic Medications for Tolerability questionnaire was used to assess patient preference and perception of side effects and activity limitations resulting from study medications. Intraocular pressure was measured before and 2 hours after the morning dose of study medication (hour 0 and hour 2). RESULTS: In both studies, among patients with a preference, the combination was preterred to timolol plus pilocarpine by a ratio of 4 to 1. The most commonly cited reason for this preference was side effects. Patients in both studies also reported that the combination interfered significantly less with daily life in terms of side effects and activity limitations. They also reported missing significantly fewer doses of study medication while taking the combination and being significantly more satisfied with it. The efficacy of these two treatments was not significantly different, based on IOP measurements at hour 0 and 2 hours after administration. Patients reported significantly more adverse events while receiving timolol plus pilocarpine in both studies, and in the U.S. study, significantly more patients discontinued therapy while receiving timolol plus pilocarpine than while receiving the combination. CONCLUSION: Compared with timolol plus pilocarpine, patients preferred the combination of 2% dorzolamide/0.5% timolol, and reported less interference in daily activities, better tolerability, and better compliance with therapy.     

Differential effects of alcohol on rod and cone temporal processing

OBJECTIVE: One of the more reliable effects of alcohol on sensory processing is the reduction of the critical flicker fusion frequency (CFF). To gain a better understanding of the mechanisms through which alcohol influences the processing of temporal information, we explored the effects of alcohol on CFF at a high level of illumination when performance is mediated by the cones (photopic), and at a lower level when performance is dominated by the rods (low mesopic). METHOD: Measurements of CFF were made under placebo and alcohol conditions (0.06% blood alcohol concentration) in six subjects (three men, three women). Assessments were obtained in both the rising and falling phases of absorption for both light levels at several retinal locations. RESULTS: Alcohol was found to reduce CFF by approximately the same amount at all retinal locations for photopic viewing levels. Mesopic CFF was lower than photopic, as expected. However, it was only minimally affected by alcohol, showing only a slight decline for central viewing. CONCLUSIONS: These results imply a selective effect on alcohol on cone function. In considering the possible mechanisms of such a selective action, we suggest that this effect may be an indirect one. That is, the poorer performance under photopic conditions may be a consequence of an alcohol-induced reduction in the inhibitory interactions that are more prevalent at photopic light levels.     

Anti-tumor ribonuclease, combined with or conjugated to monoclonal antibody MRK16, overcomes multidrug resistance to vincristine in vitro and in vivo

Onconase, a ribonuclease isolated from Rana pipiens oocytes and early embryos, is a member of the RNase A superfamily. Onconase has anti-neoplastic properties both in vitro and in vivo, and is undergoing clinical evaluation. In the present study, Onconase was combined with or conjugated to MRK16, an anti-P-glycoprotein (Pgp) monoclonal antibody. The interaction of these combinations with vincristine (VCR) against parental and multidrug resistant (MDR), Pgp expressing, human colon carcinoma cells caused increased VCR cytotoxicity in vitro and enhanced survival of athymic nude mice given transplants of drug resistant HT-29(mdr1) cells in vivo. The results suggest that combination treatment with Onconase and other agents that modulate the chemosensitivity of Pgp-expressing human tumor cells has the potential to overcome MDR.     

The clinical algorithm nosology: a method for comparing algorithmic guidelines.

Concern regarding the cost and quality of medical care has led to a proliferation of competing clinical practice guidelines. No technique has been described for determining objectively the degree of similarity between alternative guidelines for the same clinical problem. The authors describe the development of the Clinical Algorithm Nosology (CAN), a new method to compare one form of guideline: the clinical algorithm. The CAN measures overall design complexity independent of algorithm content, qualitatively describes the clinical differences between two alternative algorithms, and then scores the degree of similarity between them. CAN algorithm design-complexity scores correlated highly with clinicians' estimates of complexity on an ordinal scale (r = 0.86). Five pairs of clinical algorithms addressing three topics (gallstone lithotripsy, thyroid nodule, and sinusitis) were selected for interrater reliability testing of the CAN clinical-similarity scoring system. Raters categorized the similarity of algorithm pathways in alternative algorithms as "identical," "similar," or "different." Interrater agreement was achieved on 85/109 scores (80%), weighted kappa statistic, k = 0.73. It is concluded that the CAN is a valid method for determining the structural complexity of clinical algorithms, and a reliable method for describing differences and scoring the similarity between algorithms for the same clinical problem. In the future, the CAN may serve to evaluate the reliability of algorithm development programs, and to support providers and purchasers in choosing among alternative clinical guidelines.     

The ranges of insulin response and glucose tolerance in lean, normal, and obese women during pregnancy.

OBJECTIVE: We characterized insulin secretion and glucose disposal in a large unselected group of women, encompassing the full spectrum of glucose tolerance in pregnancy, and related the findings to maternal obesity. STUDY DESIGN: Intravenous glucose tolerance and first-phase insulin response were measured at about 32 weeks' gestation in 690 unselected pregnancies. The women were designated as "lean," "normal," or "obese" on weight-for-height criteria. RESULTS: The distribution of insulin response was bimodal, but there was no corresponding dichotomy in maternal glucose disposal rate. Insulin response was greatest and glucose disposal rate slowest in obese women. In general, "poor" glucose tolerance was associated with relatively low insulin output. It was not possible to identify any cluster of women, obese or otherwise, in whom poor glucose tolerance was specifically associated with an unusually high insulin response. CONCLUSION: The data indicate that the distribution of glucose tolerance in pregnancy is a continuum. Glucose intolerance represents one end of that spectrum and is attributable to insufficient insulin secretion. This relative insufficiency is most frequent with maternal obesity.