Capsular types and susceptibility to penicillin of pneumococci isolated from cerebrospinal fluid or blood in Denmark, 1983-1988

Subcutaneous apomorphine, administered by continuous waking-day infusion with boluses, or by repeated intermittent injection, was given to 71 parkinsonian patients with severe refractory levodopa related on-off fluctuations for 1-5 years. A mean reduction in daily off period time of approximately 50% was maintained, and the incidence of neuropsychiatric toxicity remained low on long-term follow-up. No clinically significant tolerance or loss of therapeutic effect was seen, although increasingly severe on-phase dyskinesias and postural instability marred the long-term therapeutic response in many patients. Despite these drawbacks, apomorphine, when combined with the peripheral dopamine receptor agonist domperidone, represents a significant therapeutic advance in the management of late-stage Parkinson's disease and should certainly be considered before experimental implantation procedures.     

The phenomenon of resistance to a thiazide diuretic in acute kidney failure

The resistance to hypothiazid (hydrochlorothiazide) during the development of acute renal insufficiency (ARI) induced by glycerin injection was studied in rat experiments. Natriuretic, kaliuretic, and hydrouretic activity of the diuretic decreased two days after injection of a glycerin solution. In this period hypothiazid excretion with the urine was least. Ten days later, despite the restoration of the water- and electrolyte-excretion function of the kidneys and normalization of hypothiazid excretion with the urine, the natriuretic effect of the drug was still very poor. This is indirect evidence of the long-term affection of the receptors for the thiazid diuretics during the development of ARI. The affection remains even after the excretory function of the kidneys is restored. The high correlation between the cumulative excretion of hypothiazid with the urine and natriuresis encountered in intact animals was weaker in rats with acute renal insufficiency.     

Dinitrosyl iron complexes reacts with diethyldithiocarbamate in the blood of anesthetized rats: specific physico-chemical and physiological characteristics of the products

BACKGROUND/AIMS: Portal hypertension and hyperdynamic circulation (i.e. generalized vasodilation and increased cardiac output and regional organ blood flows) may play an important role in the development of portal hypertensive gastropathy. This study investigated the effect of chronic administration of aminoguanidine, a selective inducible nitric oxide synthase inhibitor, to portal hypertensive rats on hemodynamics and the development of portal hypertensive gastropathy. METHODS: Partial portal vein-ligated or sham-operated rats were randomly assigned to receive either placebo (distilled water) or aminoguanidine (approximately 100 mg/kg per day subcutaneously) for 2 days prior to and 14 days. Hemodynamic studies with a thermodilution technique and gastric morphometric analysis were performed at 14 days after the operation. RESULTS: In rats given placebo, portal vein-ligated rats had a significantly lower mean arterial pressure and systemic vascular resistance associated with a significantly higher cardiac index and portal pressure than sham-operated rats (p<0.05). In portal vein-ligated rats aminoguanidine induced a significant increase in mean arterial pressure and systemic vascular resistance accompanied by a significant decrease in cardiac index (p<0.05) without changes in portal pressure (p>0.05). Despite persistence of portal hypertension, the aminoguanidine-treated portal vein-ligated rats had similar mean arterial pressure, cardiac index, and systemic vascular resistance as seen in placebo-treated sham-operated rats. The mean cross-sectional area of gastric mucosal vessels was significantly higher in placebo-treated portal vein-ligated than in placebo-treated sham-operated rats (p<0.05). Treatment with aminoguanidine did not induce changes in the mean cross-sectional area of gastric mucosal vessels in either portal vein-ligated or sham-operated rats (p>0.05). CONCLUSIONS: The results show that in portal hypertensive rats long-term aminoguanidine therapy corrects the hyperdynamic circulation without inducing changes in portal pressure and ameliorating the development of portal hypertensive gastropathy. This study suggests that, instead of correcting hyperdynamic circulation, treatment of portal hypertensive gastropathy should be aimed at reducing portal pressure.     

Phosphoprotein profile analysis of ruminant respiratory syncytial virus isolates

OBJECTIVE: To determine the apparent molecular weight for 24 ruminant respiratory syncytial viruses (RSV) on the basis of differences in the electrophoretic mobility of the phosphoprotein (P protein). PROCEDURE: 29 bovine RSV (BRSV), 20 of which were not previously tested, 3 ovine RSV, and 1 caprine RSV isolates were selected for determination of electrophoretic mobility of the P protein. Virus radiolabeled with [35S]methionine was immunoprecipitated with polyclonal antiserum to BRSV and analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. RESULTS: On the basis of apparent molecular size of the P protein, all isolates could be categorized into 2 electropherotypes, low molecular size of 36 kd and high molecular size of 38 kd. Twenty-three BRSV, the 3 ovine RSV, and 1 caprine RSV isolates had a high molecular size P protein; 6 BRSV isolates had a low molecular size P protein. CONCLUSIONS: The apparent molecular size of the P protein of the ruminant RSV strains is greater than that of the human RSV subgroups, providing further evidence of their distinctiveness. Whether categorization of electrophoretic mobility of the P protein of BRSV underlies distinct antigenic subgroups, as it does in human RSV, requires further antigenic and genetic analysis. CLINICAL RELEVANCE: Antigenic subgroups of ruminant RSV may have relevance in the development of new vaccines for control of the disease.     

Animal model of mucosally transmitted human immunodeficiency virus type 1 disease: intravaginal and oral deposition of simian/human immunodeficiency virus in macaques results in systemic infection, elimination of CD4+ T cells, and AIDS

Chimeric simian/human immunodeficiency virus (SHIV) consists of the env, vpu, tat, and rev genes of human immunodeficiency virus type 1 (HIV-1) on a background of simian immunodeficiency virus (SIV). We derived a SHIV that caused CD4+ cell loss and AIDS in pig-tailed macaques (S. V. Joag, Z. Li, L. Foresman, E. B. Stephens, L. J. Zhao, I. Adany, D. M. Pinson, H. M. McClure, and O. Narayan, J. Virol. 70:3189-3197, 1996) and used a cell-free stock of this virus (SHIV(KU-1)) to inoculate macaques by the intravaginal route. Macaques developed high virus burdens and severe loss of CD4+ cells within 1 month, even when inoculated with only a single animal infectious dose of the virus by the intravaginal route. The infection was characterized by a burst of virus replication that peaked during the first week following intravenous inoculation and a week later in the intravaginally inoculated animals. Intravaginally inoculated animals died within 6 months, with CD4+ counts of <30/microl in peripheral blood, anemia, weight loss, and opportunistic infections (malaria, toxoplasmosis, cryptosporidiosis, and Pneumocystis carinii pneumonia). To evaluate the kinetics of virus spread, we inoculated macaques intravaginally and euthanized them after 2, 4, 7, and 15 days postinoculation. In situ hybridization and immunocytochemistry revealed cells expressing viral RNA and protein in the vagina, uterus, and pelvic and mesenteric lymph nodes in the macaque euthanized on day 2. By day 4, virus-infected cells had disseminated to the spleen and thymus, and by day 15, global elimination of CD4+ T cells was in full progress. Kinetics of viral replication and CD4+ loss were similar in an animal inoculated with pathogenic SHIV orally. This provides a sexual-transmission model of human AIDS that can be used to study the pathogenesis of mucosal infection and to evaluate the efficacy of vaccines and drugs directed against HIV-1.     

Optimization of the diagnosis and treatment of anemias under exposure to aromatic-type organic solvents

171 iron-deficient painters and 20 subjects with chronic intoxication with aromatic hydrocarbons were studied in a large aircraft construction factory. After correlative analysis of iron metabolism, ferritin, erythrocytes, diameter and perimeter of reticulocytes, length of service three types of iron-deficiency were identified: typical, with evident toxicity, with a high risk of toxic damage. An important role of lipid peroxidation activity and toxic erythrocyto-membranopathy for pathomorphosis of iron deficiency anemia and progress of toxic anemia is demonstrated. A differential approach to treatment of different anemia variants was used. The treatment included membranoprotectors (alpha-tocopherol, essential, lypostabil) and unspecific detoxication (SUMS-enterosorbent, unitiol).