In vivo effects of nifedipine and BAY 1 8201 on ceruletide induced gallbladder contraction

Studies in animals suggest that calcium channel blockers may influence gallbladder contraction. In order to study possible actions in man we examined by ultrasonography the effects of two dihydropyridine derivatives, i.e. nifedipine (20 mg p. o.) and BAY 1 8201 (100 mg p.o.) on ceruletide induced human gallbladder contraction in 9 healthy male volunteers in a randomized, double-blind, three fold crossover study (latin square design). Blood samples for the measurement of plasma drug concentrations were drawn before and at regular intervals up to 8 h after drug ingestion. Ceruletide decreased gallbladder volumes by 52.1 +/- 8.2% (mean +/- 1 SEM) after nifedipine, 53.1 +/- 8.1% after BAY 1 8201 and by 59.3 +/- 10.1% after placebo (NS). Peak plasma concentrations of 53.7 x/: 2.3 ng/ml (geometric mean x/: geometric standard deviation) and of 35.5 x/: 1.5 ng/ml were reached after oral application of nifedipine and BAY 1 8201, respectively. We conclude that human gallbladder contraction in response to ceruletide is not markedly influenced by dihydropyridine derivates in the dosages used in this study. The results reported here stress the importance of calcium released from intracellular stores for the contractility of smooth muscle in the human gallbladder.     

Chronic Antibody Mediated Rejection of Renal Allografts: Pathological, Serological and Immunologic Features in Nonhuman Primates

The pathogenesis of late renal allograft loss is heterogeneous and difficult to diagnose. We have analyzed renal allografts in nonhuman primates to determine the relationship between alloantibodies and the graft pathology of late graft loss. Seventeen Cynomolgus monkeys were chosen from among those on several protocols for renal allotransplantation with mixed chimerism induction so that animals with and without alloantibodies were included. All animals received transient CD154 blockade and short-term cyclosporine treatment until day 28. Serial blood samples were tested for alloantibodies. Protocol biopsies and autopsy kidneys were scored for pathology and C4d deposition. Group 1, defined by complete lack of C4d deposition (24 tissue samples; 8 recipients), had no detectable alloantibodies (33 serum samples; 1-7 samples per recipient) and no evidence of chronic rejection. Three survived greater than 2 years with normal function and histology. Group 2, defined as having C4d deposition in peritubular capillaries, all made alloantibodies (100%), and most grafts later showed chronic allograft glomerulopathy (89%), and/or arteriopathy (89%). All grafts in Group 2 failed (3-27 months). Pathologic lesions of typical of chronic rejection in humans develop in monkeys, correlate with antecedent alloantibodies/C4d deposition and predict chronic rejection rather than durable accommodation.     

A prospective survey of neuroleptic malignant syndrome in a short-term psychiatric hospital

Of 1,470 patients treated with neuroleptics during 1 year at a private psychiatric hospital, only one patient developed neuroleptic malignant syndrome--an annual frequency of 0.07%. Use of low doses of neuroleptics may account for this frequency, which is below recent estimates.     

Phospholipase-A2 action and arachidonic acid metabolism in calcium-mediated parathyroid hormone secretion.

The involvement of arachidonic acid (AA) and its metabolites in the control of PTH secretion by porcine parathyroid cells was investigated. Increasing the extracellular calcium concentration from 0.5 to 2 mM increased free [3H]AA release and decreased PTH secretion from labeled parathyroid cells as a function of time (1-30 min). Free [3H]AA in the medium was significantly increased (+153 +/- 6%) after 5 min, while PTH secretion was significantly decreased (-75 +/- 7%) only after 15 min, suggesting a link between the two. [3H]AA release was associated with a decrease in [3H]AA incorporated into phosphatidylinositol, phosphatidic acid, and phosphatidylcholine, suggesting that these phospholipids are the major source of AA. Exogenous phospholipase-A2 (PL-A2; 1-500 mU/ml) and AA (5-40 microM) inhibited PTH secretion in a dose-dependent manner. PTH secretion inhibited by 2 mM Ca2+ was restored by two PL-A2 inhibitors, indomethacin (30 microM) and mepacrine (50 microM). The cyclooxygenase pathway inhibitor ibuprofen (20 microM) did not restore PTH secretion of affect high Ca(2+)-, AA-, or PL-A2-inhibited PTH secretion. Two inhibitors of the lipoxygenase pathway (LO), phenidone (1 microM) and baicalein (0.1 microM), a relatively selective 12-LO inhibitor, blunted high Ca(2+)-induced inhibition of PTH secretion (+101 +/- 10% and +105 +/- 6%, respectively), but nordihydroguaiaretic acid, which inhibits the 5-LO pathway, did not restore PTH secretion inhibited by high Ca2+, AA, or PL-A2. These results suggested that AA and agents that cause its liberation inhibit PTH secretion. AA may act via the 12-LO, but not via the 5-LO or cyclooxygenase, pathway. Thus, 12-LO products may be second messengers in parathyroid cells.     

Results of surgical treatment for atherosclerotic renovascular occlusive disease

In this study we retrospectively examined the results of surgery for atherosclerotic renal artery lesions and analysed the factors that may affect postoperative blood pressure response, changes in renal function and late mortality. A total of 326 patients were operated on over a 15 year period and were followed up for periods from 4 to 165 months (mean follow-up time: 37.2 months). An extra renal vascular area was also involved in 91.4% of cases and in 187 (57.3%) a significant involvement of both renal arteries was found and simultaneously treated. Combined revascularisation of other arteries was performed in 50.3% of patients. The indications for surgery were the treatment of extreme hypertension in 243 patients (74.5%), the improvement of renal function in 45 with renal insufficiency, and preservation of the kidney in 38 (11.7%). The preferred method of reconstruction was transaortic endarterectomy (236 cases, i.e. 72.4%) and postoperative angiography demonstrated a normal patent renal artery in 319 of 338 studied renal arteries (94.4%). There were no deaths in the early postoperative period after isolated renal artery reconstruction. Of the 164 patients with simultaneous renal and aortic reconstruction however 14 died during the early postoperative phase. The overall early mortality was thus 4.3% (14 out of 326 patients) and correlated significantly with the extent of the atherosclerotic disease, the age of the patients, the operative technique used and the different intra- and postoperative management during the two different periods of our experience (1974-1980 v. 1981-1989).(ABSTRACT TRUNCATED AT 250 WORDS)     

Crisis-related observations in competition: a case study in basketball

This study presents a unique observational approach to basketball, based on the theory of psychological performance crisis in competition. The approach used takes into account the responses of a player's actions to significant social factors such as team-mates, spectators, the coach and the referees. The contribution of this approach beyond traditional observational techniques is discussed. In our investigation, a single case design was used, in which a professional basketball player was observed during 10 home and 3 away games of the regular season. The relations between the observations and the crisis concept are discussed in detail. In addition, some relevant methodological and applied aspects are presented.     

Accidental Occupational Farm Fatalities in North Carolina: 1984 to 1988

Development of interventions to prevent accidental occupational fatalities requires the prior identification of those at risk and the circumstances surrounding the injuries. A survey of unintentional farm fatalities was conducted using medical examiner reports (RIME) and death certificates (MECD) to identify deaths due to agricultural occupational injuries in North Carolina from 1984 through 1988. Of 393 cases, 123 met the criteria "farmer" listed as occupation on the RIME/MECD and/or "victim" in a rural area performing a farming task when injured. A second aim of this study was to use an existing data base to achieve maximum accuracy in identifying true cases of work-related farm fatalities.
A fatality rate of 41/100,000 agricultural workers was found; the National Institutes of Occupational Safety and Health's National Traumatic Occupational Fatality study criteria would have identified only 57 percent of these. Victims were characterized as middle age (53 years), white (76%), male (100%), full-time farmers (65%). Injury occurred during harvest season on Monday or Tuesday (47%) between 2 and 6 p.m. (54%). Death was pronounced at the scene (74%), with probable cause listed as tractor (62%). Injury location and land elevation were also related, with the mountain region having twice the fatality rate as the coastal plains region.     

Bone marrow transplantation in miniature swine. III. Graft-versus-host disease and the effect of T cell depletion of marrow

Graft-versus-host disease (GVHD) has been evaluated in partially inbred miniature swine in order to study this complication of allogeneic bone marrow transplantation (BMT) in a major histocompatibility complex (MHC) genetically defined large animal model. Bone marrow from MHC homozygous ("parental") swine was injected into irradiated (900 rads total-body irradiation) MHC heterozygous ("F1") swine that shared one haplotype with the donor. All 18 animals successfully engrafted with donor bone marrow, and 17 of these developed skin rash of varying intensity depending on the extent of T cell depletion of infused marrow. Of 18 animals, 8 received undepleted bone marrow from exsanguinated donors and 2 also received additional peripheral blood lymphocytes (PBL) as a source of mature T cells. All 8 showed a moderate-to-severe rash, and the 2 pigs that received additional donor PBL developed the most severe rash. The cutaneous eruption seen in this model clinically, histologically, and immunologically resembled human GVHD. Two protocols of T cell depletion of donor bone marrow by antiporcine T cell monoclonal antibodies plus complement were tested for their effect on development of GVHD. The combination of two monoclonal antibodies, 74-12-4 (PT4) and 76-2-11 (PT8), had a marginal effect on the subsequent development of cutaneous manifestations of GVHD. However, treatment of the donor marrow by a combination of three monoclonal antibodies--PT4, PT8, and MSA4 (PT11)--effectively decreased the severity of the GVHD skin rash. These results indicate that (1) the GVHD associated with allogeneic bone marrow transplantation in swine is dependent on T cells in the marrow; (2) effective T cell depletion of donor marrow by monoclonal antibodies and complement does not prevent engraftment; and (3) this swine GVHD model, which allows study with F1 and homozygous parental combinations in an MHC genetically defined large animal, is particularly useful for the understanding of GVHD pathogenesis, prevention, and treatment.