Insulin and epinephrine effects on heart glycogen synthase and phosphorylase activity.

The effect of intravenous epinephrine on heart glycogen synthase and phosphorylase systems in control and insulin-pretreated rats was studied. The percent of synthase in the I form decreased rapidly after epinephrine treatment but the change was small and sometimes not significant. In insulin-pretreated rats in which the percent synthase I was increased, epinephrine produced a definate and highly significant decrease. There was a simultaneous increase in percent phosphorylase a in both groups. The synthase and phosphorylase responses were statiscally significant at 2.5 mug epinephrine/kgor more. These data are compatible with a mechanism in which protein kinase is activated by an increased cAMP concentration and affects both the synthase and phosphorylasesystems simultaneously. Propranolol blocked the epinephrine effects on cAMP, synthase I, and phosphorylase a. Although insulin had little effect on the response ofthe synthase and phosphorylase systems to epinephrine, it nealry completely blocked glycogen degradation. The mechanism is unknown, but it appears to be due to an inhibition of phosphorylase a catalytic activity in vivo. Acetylcholine had no effect on synthase I, phosphorylase a, or cAMP in control or in insulin-pretreated animals.     

Psychophysiological correlates of induced headaches

The psychophysiological correlates of induced headaches were examined. Subjects with frequent muscle-contraction headaches, frequent migraine headaches, or infrequent headaches were exposed to a 1-h cognitive stressor while multiple electromyographic and cardiovascular measures were monitored. The stressor was associated with significant changes in all psychophysiological measures. Eleven of 16 headache subjects and 2 of 8 control subjects developed headaches. Significant associations between several psychophysiological variables and headache occurrence were found and individual differences in the association between psychophysiological variables and headaches intensity were examined. The results were consistent with the hypothesized role of cardiovascular factors in the pathophysiology of muscle-contraction headache. This was the first controlled demonstration of headaches occurring as a function of environmental stressors.This research was supported by Grant 5-R01-NS-1875 from the National Institute of Health.     

MR imaging with surface coils

The use of specialized coils to improve signal-to-noise ratios in magnetic resonance (MR) imaging is an important innovation. The role of surface coils has not yet been well defined, but it seems likely that they will be routinely used for clinical imaging of the orbit, neck, and spine. Surface coils have important limitations that make other designs, such as "closely coupled" volume coils, attractive for some applications, especially for limb imaging. With improvement in our ability to visualize anatomy with MR imaging, specialized radio frequency coils may provide new imaging capabilities for clinical problems that were not previously considered to be indications for diagnostic imaging.     

The use of natural interferon alpha conjugated to a monoclonal antibody anti mammary epithelial mucin (Mc5) for the treatment of human breast cancer xenografts

Summary An immunoconjugate composed of natural interferon (nIFN) bound in a noncleavable fashion to a monoclonal antibody (MoAb) recognizing a breast epithelial membrane mucin (Mc5) was used to treat xenografts of a human mammary carcinoma cell line (MCF-7) growing in nude mice. The immunoconjugate (nIFN/Mc5) was administered as 20 intralesional (i.l.) injections to 1 of 2 xenografts in each animal. It was found that nIFN/Mc5 produced a significant enhancement of the growth inhibitory actions of nIFN on the injected tumors. Further enhancement was obtained when nIFN or nIFN together with Mc5 (at a dose 10 times larger than that present in nIFN/Mc5) were added to the immunoconjugate. Biodistribution experiments showed that the uptake of¹²⁵I-nIFN/Mc5 by the tumors was greater and its elimination slower than for¹²⁵I-nIFN alone or conjugated to irrelevant mouse IgG₁. In addition, the immunoconjugate up-regulated the antigenic expression of a breast epithelial membrane mucin by the carcinoma cells, an up-regulation which was not significantly different from that produced by nIFN alone. The contralateral noninjected tumors exposed to systemic levels of the immunoconjugate showed an enhancement of antitumor effects, but to a lesser extent than the injected tumors. These findings suggest that the enhancement of the growth inhibitory action of the immunoconjugate was related to the specific binding of Mc5 which targeted the IFN to the carcinoma cells and impeded its elimination. It is likely that the targeting was favored by the IFN-mediated up-regulation of antigenic expression by the carcinoma cells, thereby producing a cascade of interrelated effects. The results of this study point out the feasibility and potential usefulness of IFN treatment by means of immunoconjugates as well as the worth of pursuing and improving this form of therapy.     

Evaluation of i.v. ceftriaxone usage in a community-based hospital

Ceftriaxone is primarily used for the treatment of gram-negative nosocomial pneumonia and for gram-negative bacteremias. The following study examines whether ceftriaxone, a broad spectrum parenteral cephalosporin antibiotic, was being administered appropriately based on pre-established hospital criteria.     

Developing staff into clinical practitioners

Developing clinical skills in pharmacy staff is a process that can enhance the services of a pharmacy department and improve the professional development and interest of the staff. Staff should be included in the development of a clinical philosophy and a training and ongoing development program that will achieve the desired goals should be planned. An MBO process may help to track the individual pharmacist's progress. Knowledgeable, motivated staff are the key ingredient in achieving success in providing pharmacy services.     

Regional cycles of perfusion and non-perfusion in the lung of the term fetal rabbit.

The spatial distribution of pulmonary blood flow and its change over time was investigated in term fetal rabbits, using the plasma tracer fluorescein-isothiocyanate-labeled bovine serum albumin (FITC-BSA). A tracer bolus was injected intravenously and allowed to circulate in vivo for increasing periods of time (2-30 minutes) prior to arrest of the circulation and tissue preparation. Initially, fluorescence was present in the vasculature of 43% of lung parenchymal tissue, disposed as discrete regions or "lobules." Interspersed regions of lung tissue received no tracer inflow. With increasing tracer circulation times (10, 20, and 30 minutes), a greater percentage of lung cross-sectional area contained vessels exhibiting tracer fluorescence (64, 96, and 100%, respectively). In the fetal lung, a high pulmonary vascular resistance (PVR) is maintained. Our studies indicate that, at any given moment, fetal pulmonary blood flow is distributed only to a proportion of discrete lung "lobules," while interspersed "lobules" receive no flow at all. The "lobules" alternate between these "high" and "low" vascular resistance states with a periodicity of approximately 35 minutes, comprising 22 minutes of non-perfusion followed by 13 minutes of perfusion. This circulatory pattern permits both the maintenance of high PVR and uniform lung development. Further, by directing flow to only a portion of the vasculature, greater microvascular flow rates are achieved and hence the risk of blood sludging and stasis is reduced. Recruitment of these "non-perfused" regions at birth could thus produce a significant reduction in PVR.