Attenuation of bovine parainfluenza virus type 3 in nonhuman primates and its ability to confer immunity to human parainfluenza virus type 3 challenge

Bovine parainfluenza virus type 3 (PIV-3) was evaluated as a candidate live-virus vaccine to protect against infection with human PIV-3. The level of replication of bovine and human PIV-3 and the efficacy of immunization with bovine PIV-3 in protecting against subsequent challenge with human PIV-3 was evaluated in nonhuman primates. The duration and magnitude of replication of human and bovine PIV-3 in the upper and lower respiratory tracts of New World monkeys was similar, and animals infected with bovine PIV-3 developed resistance to challenge with human PIV-3. The replication of two bovine strains of PIV-3 was restricted 100- to 1000-fold in Old World primates but was sufficient to induce high levels of neutralizing antibody to human PIV-3. The combined properties of restricted replication and induction of a protective immune response to human PIV-3 in nonhuman primates make bovine PIV-3 a promising candidate for a live-virus vaccine to protect humans against disease caused by PIV-3.     

Adinazolam, diazepam, imipramine, and placebo in major depressive disorder: a controlled study.

In summary, the clinical results of this double-blind study clearly show that imipramine, as expected, demonstrated significant antidepressive properties in outpatients suffering from major depressive disorders. In contrast, adinazolam showed rather mild and weak antidepressive properties, and in no measures did its response differ significantly from that of diazepam. These findings are quite in contrast to those obtained by the authors in an earlier study with alprazolam (Rickels et al., 1987) in which alprazolam and imipramine produced rather similar results and both were significantly better than placebo, while diazepam was not. While the rather high dropout rate may well be considered a limitation of the study, the dropout rate is equally distributed between all four treatments. And since both decreasing sample size and endpoint analyses which include all patients with at least one week data, provide rather similar results, the findings can be considered as robust despite the high dropout rate. While the authors consider those findings the most robust in which endpoint and completer analyses results are rather similar, when high dropout rates occur, endpoint analyses should be given more weight than completer analyses as they are more representative of actual clinical practice. The present findings therefore suggest that adinazolam clearly possesses less antidepressive properties than imipramine and not more than diazepam and these findings are in agreement with other studies which found lack of significant antidepressant activity for such benzodiazepines as diazepam (Covi et al., 1974) and chlordiazepoxide (Lipman et al., 1986). The presence of only borderline antidepressive effects combined with rebound symptoms occurring already after only 6 weeks of therapy does not recommend adinazolam for use in depression.(ABSTRACT TRUNCATED AT 250 WORDS)     

The renal handling of beta 2-microglobulin in the dog

The renal extraction of beta 2-microglobulin (beta 2M) was investigated under steady-state conditions achieved by constant infusion of human beta 2M. Fifteen animal experiments were conducted. Beta 2 microglobulin was infused at rates ranging from 51 o 269 micrograms/min. The renal arterial and venous blood levels remained constant throughout the study period. The data showed that renal extraction of beta 2M exceeded the rate of filtration at all levels of beta 2M delivered to the kidney. The tubular uptake of filtered beta 2M increased linearly as did the extraglomerular extraction throughout the range investigated. There was no evidence of beta 2M (FE beta 2M) increased linearly with the fractional excretion of filtered water (FE H2O). The results are interpreted to indicate that beta 2M is extracted from renal blood by glomerular filtration and, in addition, by a mechanism independent of glomerular filtration rate (GFR). Under the conditions existing in these experimental animals, the linear relationship between FE beta 2M and FE H2O is evidence to suggest that factors affecting proximal tubular water reabsorption also affect beta 2M reabsorption.     

A study of the susceptibility of three species of primate to vaginal colonization with Gardnerella vaginalis.

In an attempt to develop an animal model of Gardnerella-associated vaginitis, several strains of Gardnerella vaginalis were inoculated into the lower genital tract of female pig-tailed macaques, tamarins and chimpanzees. G. vaginalis was not recovered from either tamarins or chimpanzees, but was recovered from each of 1O pig-tailed macaques inoculated with either of two freshly isolated Gardnerella strains, colonization persisting for 11-39 days. Examination of Gram-stained vaginal smears obtained from infected pig-tailed macaques failed to demonstrate clue cells, a feature which is pathognomonic of Gardnerella-associated vaginitis in humans. Other features characteristic of non-specific vaginitis, namely an increase in vaginal pH, and an increase in the ratio of succinate to lactate (S/L ratio) in vaginal fluid were not found. However, the physiology of the macaque vagina was found to be different from that of the human, the vaginal pH and S/L ratio of uninfected macaques both being higher than that seen in humans. The physiological differences between the macaque and human vagina may be due, in part, to a difference in their anaerobic vaginal flora. While these inter-species differences in vaginal physiology and microbiology limit the relevance of the pig-tailed macaque as a model of Gardnerella-associated vaginitis, the ease with which macaques are colonized with G. vaginalis may prove useful in studying bacterial adhesion and local immunity.     

Arterial media calcification in end-stage renal disease: impact on all-cause and cardiovascular mortality.

BACKGROUND: Cross-sectional and follow-up studies on end-stage renal disease patients showed that arterial calcifications are associated with cardiovascular (CV) morbidity and are an independent predictor of all-cause and CV mortality. However, these studies did not examine the impact on prognosis according to the type of calcification, i.e. intimal vs medial. Arterial media calcification (AMC), a non-occlusive condition, affects haemodynamics differently from arterial intima calcification (AIC), which occurs in atherosclerotic plaques. The aim of this study was to investigate the prognostic value of AMC in relationship to all-cause or CV mortality for stable haemodialysis (HD) patients. METHODS: We included 202 such patients in the present study. At baseline, soft-tissue native radiograms of the pelvis and the thigh were analysed for the presence and type (AMC vs AIC) of arterial calcifications. All patients underwent B-mode ultrasonography of the common carotid artery to determine the presence of atherosclerotic calcified plaques, measurement of aortic pulse wave velocity and echocardiography. RESULTS: AIC was usually observed in older patients with a clinical history of atherosclerosis before starting HD treatment and typical risk factors associated with atherosclerotic disease. AMC was observed in young and middle-aged patients without conventional atherosclerotic risk factors. AMC was closely associated with the duration of HD and calcium-phosphate disorders, including the oral dose of elemental calcium prescribed as phosphate binder (CaCO(3)). Compared to patients with AIC, patients with AMC had a longer survival, but in turn their survival was significantly shorter than that of patients without calcifications. CONCLUSIONS: AMC is a strong prognostic marker of all-cause and CV mortality in HD patients, independently of classical atherogenic factors. The principal effect of AMC on arterial function is increased arterial stiffness.     

A comparison of six statins on the development of intimal hyperplasia in a human vein culture model.

OBJECTIVE: Intimal hyperplasia (IH) threatens the patency of up to 35% of saphenous vein (SV) bypass grafts. In addition to reducing cholesterol levels, statins may modulate smooth muscle cell proliferation and migration. Statins inhibit matrix metalloproteinase (MMP) activity. We therefore investigated the effect of six statins on neointimal formation and MMP activity in human SV organ culture. STUDY DESIGN: Human SV specimens were cultured for 14 days in the presence of six different statins and subsequently processed for measurement of neointimal thickness and MMP activity. The drug concentrations chosen corresponded to the manufacturers' Cmax. RESULTS: The six statins all significantly reduced IH development (P = 0.004) in association with reduced expression of proMMP-2 and 9 (P = 0.03) and reduced activity of activated MMP-2 and 9 (P = 0.03). CONCLUSION: This study suggests that the potential benefit of statins in reducing IH is a class effect and not confined to specific statins. The reduction of IH produced by statins may in part be due to their inhibition of MMPs.     

Contrast-enhanced abdominal computed tomography scanning and prediction of severity of acute pancreatitis: a prospective study

One hundred and fifty-two patients were admitted to a single hospital with a diagnosis of acute pancreatitis during a 31-month period. Of these, 126 patients had contrast-enhanced abdominal computed tomography (CT) scans within 72 h of admission; 92 of these attacks were clinically mild, 34 were clinically severe. A single consultant radiologist reported the scans 'blind' and noted whether pancreatic enhancement was normal, increased or decreased, and whether there was loss of peripancreatic tissue planes. The maximum anteroposterior measurement of the pancreatic head and body were multiplied together to produce a 'pancreatic size index' (cm2). Significantly more patients with severe attacks had decreased pancreatic enhancement (79 versus 58 per cent, P = 0.01) and loss of peripancreatic tissue planes (82 versus 54 per cent, P = 0.006). The median (range) pancreatic size index for clinically severe attacks was 12.8 cm2 (3.0-52.5), and for mild attacks was 6.0 cm2 (1.1-23.4), P less than 0.0001. Modified Glasgow criteria had a sensitivity of 85 per cent and specificity of 79 per cent for clinically severe attacks. A pancreatic size index of greater than or equal to 10 cm2 had a sensitivity of 71 per cent and specificity of 77 per cent for clinically severe attacks. In conclusion, although there were highly significant differences between the clinically severe and mild groups with respect to pancreatic enhancement, peripancreatic tissue planes and pancreatic size indices, these CT criteria did not improve on modified Glasgow criteria for prediction of disease severity.