Effect of tylosin tartrate on humoral immune responses in chickens

This article examines the 50-year struggle of osteopathic physicians to gain entry into the US Military Medical Corps on the same basis as allopathic physicians. The author explores various arguments put forth by both physician groups, as well as those arguments presented by the respective surgeons general and relevant government officials.     

High- versus low-dose ACE inhibition in chronic heart failure: a double-blind, placebo-controlled study of imidapril

OBJECTIVES: To determine dose-related clinical and neurohumoral effects of angiotensin-converting enzyme (ACE) inhibitors in patients with chronic heart failure (CHF), we conducted a double-blind, placebo-controlled, randomized study of three doses (2.5 mg, 5 mg and 10 mg) of the long-acting ACE inhibitor imidapril. BACKGROUND: The ACE inhibitors have become a cornerstone in the treatment of CHF, but whether high doses are more effective than low doses has not been fully elucidated, nor have the mechanisms involved in such a dose-related effect. METHODS: In a parallel group comparison, the effects of three doses of imidapril were examined. We studied 244 patients with mild to moderate CHF (New York Heart Association class II-III: +/-80%/20%), who were stable on digoxin and diuretics. Patients were treated for 12 weeks, and the main end points were exercise capacity and plasma neurohormones. RESULTS: At baseline, the four treatment groups were well-matched for demographic variables. Of the 244 patients, 25 dropped out: 3 patients died, and 9 developed progressive CHF (3/182 patients on imidapril vs. 6/62 patients on placebo, p < 0.05). Exercise time increased 45 s in the 10-mg group (p = 0.02 vs. placebo), but it did not significantly change in the 5-mg (+16 s), and 2.5-mg (+11 s) imidapril group, compared to placebo (+3 s). Physical working capacity also increased in a dose-related manner. Plasma brain and atrial natriuretic peptide decreased (p < 0.05 for linear trend), while (nor)epinephrine, aldosterone and endothelin were not significantly affected. Renin increased in a dose-related manner, but plasma ACE activity was suppressed similarly (+/-60%) on all three doses. CONCLUSIONS: Already within 3 months after treatment initiation, high-dose ACE inhibition (with imidapril) is superior to low-dose. This is reflected by a more pronounced effect on exercise capacity and some of the neurohormones, but it does not appear to be related to the extent of suppression of plasma ACE.     

Increased MPTP neurotoxicity in vesicular monoamine transporter 2 heterozygote knockout mice

The neurotoxic action of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) has been proposed to be attenuated by sequestration into intracellular vesicles by the vesicular monoamine transporter (VMAT2). The purpose of this study was to determine if mice with genetically reduced levels of VMAT2 (heterozygote knockout; VMAT2 +/-) were more vulnerable to MPTP. Striatal dopamine (DA) content, the levels of DA transporter (DAT) protein, and the expression of glial fibrillary acidic protein (GFAP) mRNA, a marker of gliosis, were assessed as markers of MPTP neurotoxicity. In all parameters measured VMAT2 +/- mice were more sensitive than their wild-type littermates (VMAT2 +/+). Administration of MPTP (7.5, 15, or 30 mg/kg, b.i.d.) resulted in dose-dependent reductions in striatal DA levels in both VMAT2 +/- and VMAT2 +/+ animals, but the neurotoxic potency of MPTP was approximately doubled in the VMAT2 +/- mice: 59 versus 23% DA loss 7 days after 7.5 mg/kg dose for VMAT2 +/- and VMAT2 +/+ mice, respectively. Dopaminergic nerve terminal integrity, as assessed by DAT protein expression, also revealed more drastic reductions in the VMAT2 +/- mice: 59 versus 35% loss at 7.5 mg/kg and 95 versus 58% loss at 15 mg/kg for VMAT2 +/- and VMAT2 +/+ mice, respectively. Expression of GFAP mRNA 2 days after MPTP was higher in the VMAT2 +/- mice than in the wild-type: 15.8- versus 7.8-fold increase at 7.5 mg/kg and 20.1- versus 9.6-fold at 15 mg/kg for VMAT2 +/- and VMAT2 +/+ mice, respectively. These observations clearly demonstrate that VMAT2 +/- mice are more susceptible to the neurotoxic effects of MPTP, suggesting that VMAT2-mediated sequestration of the neurotoxin into vesicles may play an important role in attenuating MPTP toxicity in vivo.     

A new blood compatible and permselective hollow fiber membrane for hemodialysis

The authors have prepared a blood compatible and highly permselective hemodialysis membrane composed of polyether segmented nylon. This block copolymer was synthesized by polycondensation of bis-3-aminopropyl-poly(tetramethylene oxide) (PTMO) and poly(imino-1,3-bismethyl-cyclohexyl-iminoisophtharoyl) (NyBl) prepolymer obtained by polycondensation of 1,3-bis(aminomethyl)cyclohexane (B) and isophthalic acid (I). The molecular weight (MW) calculated from the number of end-groups was 16,000-21,000. In vitro blood compatibility was evaluated in terms of platelet adhesion onto the surface. PTMO-NyBl surfaces showed excellent platelet adhesion preventing properties. The PTMO-NyBl hollow fiber membrane was obtained by a dry-wet spinning process. The membranes had higher permeability coefficients for macromolecules ranging from MW 10,000 to 20,000 than polysulfone hollow fiber membrane (PS membrane), and had acceptably low albumin permeability for use as a dialysis membrane. The ex vivo blood compatibilities of PTMO-NyBl membrane and PS membrane were investigated by extracorporeal circulation in a pig model. The PTMO-NyBl membrane gave excellent results when assessing hemodialysis leukopenia, oxidative burst, and free platelet count decrease.     

Synthesis and evaluation of 5-aminosalicyl-glycine as a potential colon-specific prodrug of 5-aminosalicylic acid

OBJECTIVE: To estimate more precisely the risk of fetal loss and congenital abnormalities after maternal parvovirus B19 infection, and to assess the long term outcome for surviving infants. DESIGN: Prospective cohort study of pregnant women with confirmed B19 infection with follow up of the surviving infants. The rate of fetal loss in the study cohort was compared with that in pregnant women with varicella. SETTING: Cases reported by laboratories in England and Wales between 1985-1988 and 1992-1995. SAMPLE: Four hundred and twenty-seven pregnant women with B19 infection and 367 surviving infants of whom 129 were followed up at 7-10 years of age. METHODS: Questionnaires to obstetricians and general practitioners on outcome of pregnancy and health of surviving infants. Maternal infection confirmed by B19-specific IgM assay and/or IgG seroconversion. RESULTS: The excess rate of fetal loss in women with B19 infection was confined to the first 20 weeks of gestation and averaged 9%. Seven cases of fetal hydrops followed maternal infections between 9 and 20 weeks of gestation (observed risk 2.9%, 95% CI 1.2-5.9). No abnormalities attributable to B19 infection were found at birth in surviving infants (observed risk 0%, upper 95% CI 0.86%). No late effects were found at 7-10 years. CONCLUSIONS: Around 1 in 10 women infected before 20 weeks of gestation will suffer a fetal loss due to B19. The risk of an adverse outcome of pregnancy after this stage is remote. Infected women can be reassured that the maximum possible risk of a congenital abnormality due to B19 is under 1% and that long term development will be normal.     

Multihormone-producing islet cell tumor of the pancreas associated with somatostatin-immunoreactive amyloid: immunohistochemical and immunoelectron microscopic studies

OBJECTIVE: To assess the association between high but nondiabetic blood glucose levels and the risk of death from all causes, coronary heart disease (CHD), cardiovascular disease, and neoplasms. RESEARCH DESIGN AND METHODS: We studied the 20-year mortality of non-diabetic, working men, age 44-55 years, in three European cohorts known as the Whitehall Study (n = 10,025), the Paris Prospective Study (n = 6,629), and the Helsinki Policeman Study (n = 631). These men were identified by their 2-h glucose levels following an oral glucose tolerance test and by the absence of a prior diagnosis of diabetes. As the protocol for the oral glucose tolerance test and methods for measuring glucose differed between studies, mortality was analyzed according to the percentiles of the 2-h and fasting glucose distributions, using the Cox's proportional hazards model. RESULTS: Men in the upper 20% of the 2-h glucose distributions and those in the upper 2.5% for fasting glucose had a significantly higher risk of all-cause mortality in comparison with men in the lower 80% of these distributions, with age-adjusted hazard ratios of 1.6 (95% CI 1.4-1.9) and 2.0 (1.6-2.6) for the upper 2.5%. For death from cardiovascular and CHD, men in the upper 2.5% of the 2-h and fasting glucose distributions were at higher risk, with age-adjusted hazard ratios for CHD of 1.8 (1.4-2.4) and 2.7 (1.7-4.4), respectively. CONCLUSIONS: If early intervention aimed at lowering blood glucose concentrations can be shown to reduce mortality, it may be justified to lower the levels of both 2-h and fasting glucose, which define diabetes.     

Temperature dependence of the vortex nucleation field of thin-film,type II superconductors

The critical supercurrent versus applied field parallel to the surface of Pb-20 wt % In thin films was measured at various temperatures. The temperature dependence of the first vortex nucleation field (the lower critical field of a thin-film superconductor) suggests that the vortex structure is distorted due to surface effects.