CNS 7065 is a high-affinity and selective ligand for the benzodiazepine site on the GABAA receptor. CNS 7056 does not show selectivity between GABAA receptor subtypes. CNS 7056 is a potent sedative in rodents with a short duration of action. Inhibition of substantia nigra pars reticulata firing and the inhibition of the effects of CNS 7056 by flumazenil show that it acts at the brain benzodiazepine receptor.
Two ovarian cell lines were derived from the ascites of a patient before and after the onset of resistance to chemotherapy involving cis-platinum, chlorambucil and 5-fluorouracil. Characterization of these lines shows them to have various features in common and some significant differences. Cytologically the lines cannot be distinguished and they both contain high concentrations of oestrogen receptor. However, they do differ with respect to their growth characteristics, karyotype, glutathione content and sensitivity to cis-platinum. The karyotypes of the 2 lines show several marker chromosomes in common but the resistant line contained a chromosome 8 and a 17 which were absent from the earlier sensitive line. This suggests a clonal origin with subsequent divergence to a heterogeneous population.
Signal phase variations caused by physiology are a major source of instability in fMRI images produced by multiple RF pulses. k-Space phase variation maps show cyclic phase variations at the frequency of respiration combined with a cardiac variation of lower amplitude. The amplitude of the variation increases with gradient echo time and proximity to the chest, suggesting that the dominant cause of the phase variation is a B0 shift (approximately 0.01 ppm) produced by movement of organs in the chest. A simple k-space phase correction method is proposed and demonstrated for FLASH fMRI. The retrospective method requires no pulse sequence modification, and is more effective than navigator echo correction. Physiological noise is dramatically reduced, especially at inferior slice locations.
Alginate-polylysine microencapsulation has been proposed as a method of protecting transplanted pancreatic islets against immunological attack. Using this technique, prolonged graft survival has been reported in some diabetic animals. However, in the spontaneously diabetic insulin-dependent BB/E rat we found that intraperitoneal implantation of microencapsulated islets had only a short-lived effect on hyperglycaemia. Recovered microcapsules (both those implanted empty and containing islets) were surrounded by a foreign body type cellular overgrowth and, although many capsules remained intact, encapsulated islets were observed to be disintegrating. Loss of Beta cells was confirmed by immunohistology. Various polymer materials used in artificial membranes have been shown to activate macrophages involved in foreign body reactions and induce synthesis of interleukin-1 beta, a known Beta-cell toxin. Reduced secretion of insulin and progressive islet damage (indicated by a significant reduction in residual islet insulin and DNA content) were demonstrated when microencapsulated islets were incubated with interleukin-1 beta in vitro for 9 days. Similar effects were seen following exposure to a combination of gamma interferon and alpha tumour necrosis factor. Successful use of microencapsulation in islet transplantation depends upon the development of biocompatible membranes. The exclusion of smaller molecules, such as cytokines, which may be involved in foreign body mediated damage and microencapsulated islet graft rejection, could also be important.
Surveillance of infectious episodes in institutionalized elderly men permanently resident on two wards of a veterans' hospital was undertaken for a 12-month period. One-hundred eleven episodes were identified in 50 residents (74 per cent). The most frequent infections included lower respiratory tract infections (incidence 59/100 patient-years), febrile episodes with no source (43.4), skin and soft tissue infections (36.5), and gastroenteritis (33). Only pneumonia was associated with significant mortality. A specific etiologic agent was seldom identified other than for skin and soft tissue infections. Antimicrobial therapy was prescribed for 87 per cent of all infections. Ward staff absenteeism was associated with peak occurrences of infections in residents. Resident characteristics that correlated with infection were incontinence of bladder and of bowel. Mental status or degree of mobility did not correlate. While infections occur frequently in this population, mortality is common only with pneumonia. Infections occur more frequently in residents who have greater functional impairment.
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