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Some persons who have had diabetes for many years develop gastroparesis, in which the stomach does not contract and empty normally. Food remains in the stomach, which can cause vomiting. Gastroparesis is particularly detrimental for diabetics, because erratic or delayed stomach emptying means that energy (calories) will not be absorbed into the bloodstream in a predictable fashion; as a result, blood sugar is even more difficult to control than in uncomplicated diabetes mellitus. The motility, or movements, of the stomach can be stimulated with the natural protein motilin, but unfortunately research on this substance has been limited by its high cost. The antibiotic erythromycin appears to be an effective substitute for motilin, and so it may be useful in treating gastrointestinal motility disorders. Ten subjects with diabetic gastroparesis were given erythromycin or an inert placebo intravenously, and the emptying of liquids and solids from the stomach was assessed. Ten normal controls were also studied. Erythromycin brought stomach emptying time to normal in the diabetics; two hours after eating, 63 percent of the food remained in the stomach with placebo but only 4 percent was retained with erythromycin. Controls had 9 percent of food remaining. The diabetics were then treated for four weeks with oral erythromycin, which increased stomach motility, but not as well as the intravenous therapy. From this preliminary study, it appears that erythromycin may be beneficial in treating diabetic gastroparesis. (Consumer Summary produced by Reliance Medical Information, Inc.)

The role of extracellular α-synuclein (α-syn) in the initiation and the spreading of neurodegeneration in Parkinson's disease (PD) has been studied extensively over the past 10 years. However, the nature of the α-syn toxic species and the molecular mechanisms by which they may contribute to neuronal cell loss remain controversial. In this study, we show that fully characterized recombinant monomeric, fibrillar or stabilized forms of oligomeric α-syn do not trigger significant cell death when added individually to neuroblastoma cell lines. However, a mixture of preformed fibrils (PFFs) with monomeric α-syn becomes toxic under conditions that promote their growth and amyloid formation. In hippocampal primary neurons and ex vivo hippocampal slice cultures, α-syn PFFs are capable of inducing a moderate toxicity over time that is greatly exacerbated upon promoting fibril growth by addition of monomeric α-syn. The causal relationship between α-syn aggregation and cellular toxicity was further investigated by assessing the effect of inhibiting fibrillization on α-syn-induced cell death. Remarkably, our data show that blocking fibril growth by treatment with known pharmacological inhibitor of α-syn fibrillization (Tolcapone) or replacing monomeric α-syn by monomeric β-synuclein in α-syn mixture composition prevent α-syn-induced toxicity in both neuroblastoma cell lines and hippocampal primary neurons. We demonstrate that exogenously added α-syn fibrils bind to the plasma membrane and serve as nucleation sites for the formation of α-syn fibrils and promote the accumulation and internalization of these aggregates that in turn activate both the extrinsic and intrinsic apoptotic cell death pathways in our cellular models. Our results support the hypothesis that ongoing aggregation and fibrillization of extracellular α-syn play central roles in α-syn extracellular toxicity, and suggest that inhibiting fibril growth and seeding capacity constitute a viable strategy for protecting against α-syn-induced toxicity and slowing the progression of neurodegeneration in PD and other synucleinopathies. [ABSTRACT FROM AUTHOR]

We define an iterative procedure to obtain a non-abelian generalization of the BornInfeld action. This construction is made possible by the use of the severe restrictions imposed by kappa-symmetry. We have calculated all bosonic terms in the action up to terms quartic in the Yang-Mills field strength and all fermion bilinear terms up to terms cubic in the field strength. Already at this order the fermionic terms do not satisfy the symmetric trace-prescription. [ABSTRACT FROM AUTHOR]

Background: The optimal atrioventricular delay in dual-chamber pacing differs from patient to patient. The availability of a portable scintillation probe (VEST) enables noninvasive monitoring of left ventricular function.Methods and Results: Hemodynamic variations were measured in 10 patients with programmable DDD pacemakers. The ejection fraction, stroke volume, and diastolic and systolic volume were evaluated, programming six different atrioventricular delays ranging from 75 to 200 msec, to determine the most favorable atrioventricular delay. Comparing left ventricular ejection fraction (LVEF), stroke volume, and end-diastolic and end-systolic volume at each DVI mode with a preceding DVI setting of 75 msec, all parameters at 200 msec were statistically different from those at 100 msec. An increase of LVEF and stroke volume and a decrease of end-systolic volume was found. In only five patients a switch of VVI mode to the optimal DVI mode results in an increase of LVEF of more than 5%.Conclusions: Our study stresses the importance of optimizing atrioventricular delay. The VEST system permits these measurements, increasing the accuracy of the determination of optimal atrioventricular delay, and appears to be valuable in the management of patients with cardiac dual-chamber pacemakers. [ABSTRACT FROM AUTHOR]

This report describes the diagnostic contribution of gallium-67 scintigraphy in 145 cases of fever of unknown origin (FUO) at University Hospital in Leuven, Belgium, in 1980–1989. A final diagnosis was established in 99 (68%) of the 145 cases. Sixty-three scans (43%) were normal, and 82 (57%) were abnormal; only 42 of the abnormal scans (29% of the total number of scans) were considered helpful in diagnosis. Thus 49% of the abnormal scans were considered noncontributory to the diagnosis. In the same population, 15 (6%) of 266 ultrasonograms and 32 (14%) of 233 computed tomograms were helpful in diagnosis. We conclude that gallium scintigraphy remains a valuable screening tool in the investigation of FUO: it yielded diagnostic information in 29% of cases in which the probability of a definitive diagnosis was only 68%. We suggest the use of gallium scintigraphy as a second-step (as opposed to a last-resort) procedure in the evaluation of FUO. [ABSTRACT FROM PUBLISHER]

Serum vitamin D metabolites and urinary calcium excretion; parameters of bone formation (serum alkaline phosphatase, serum osteocalcin); parameters of bone resorption (24 hour hydroxyprolinuria, 2 hour fasting urinary hydroxyproline/creatinine ratio); and parameters of cortical and trabecular bone density, parathyroid hormone (iPTH, COOH terminal assay), and serum minerals (calcium, phosphorus) were followed serially in 55 young adults (21 women and 34 men) from December 1985 until January 1987 at four different times during the year. The effect of a low-dose cyclooxygenase inhibitor (piroxicam 5 mg daily) on the same parameters of bone density and bone turnover when given from December until May, was also evaluated in this study. At the end of the treatment period parameters of bone turnover and bone density were comparable between placebo and piroxicam-treated groups. Therefore, the results of all subjects were pooled in order to investigate seasonal variation. In both sexes, seasonal variation was found not only for 250HD3 but also for 1,25(OH)2D3, serum calcium and phosphorus, urinary calcium excretion, and for bone density at the lumbar spine. Parameters of bone formation (serum osteocalcin and alkaline phosphatase), bone resorption (24 hour urinary hydroxyprolinuria and fasting urinary hydroxyproline/creatinine ratio) and PTH were influenced by this seasonal variation. We conclude that in young adults, a significant seasonal variation occurs, with low winter and high summer values, for serum 25 and 1,25(OH)2D3 for urinary calcium apparently without important influence on parameters of bone turnover or parathyroid activity and for lumbar spine density. Treatment with a low-dose cyclooxygenase inhibitor was without influence on the observed changes. [ABSTRACT FROM AUTHOR]