Adrenergic,purinergic, and endothelial mediators and modulators of norepinephrine-induced mesenteric autoregulatory escape

We evaluated the effects of potential factors in autoregulatory escape from norepinephrine-induced vasoconstriction in rat anterior mesenteric artery. We determined mesenteric artery blood flow velocity with a pulsed Doppler, sonic flowmeter, and systemic arterial blood pressure with a transducer. A 4-min norepinephrine infusion (0.125–1.0 × 10^–8 M/min) intravenously evoked a dose-dependent, initial vasoconstriction that was followed by rapid escape of blood flow toward or above the control value during sustained norepinephrine administration. Neonatal capsaicin treatment enhanced vasoconstrictor responses to norepinephrine but failed to affect escape parameters. Propranolol decreased norepinephrine-induced escape dose dependently. Adenosine deaminase attenuated escape, and the combination of this enzyme plus propranolol nearly abolished escape from norepinephrine-induced vasoconstriction. Methylene blue also diminished autoregulatory escape. These findings suggest that norepinephrine-induced autoregulatory escape involves simultaneous -adrenoceptor, purinergic, and endothelial mediation. Norepinephrine-evoked mesenteric vasoconstriction appears to involve predominantly ₂-adrenoceptors and is modulated by peptidergic sensory nerves and adenosine.NIH grant number supporting these studies: USPHS # DK37050.     

Observations on the recent epizootic of bovine ephemeral fever in Saudi Arabia

Observations of the epizootic of bovine ephemeral fever which occurred in Saudi Arabia during 1996 are presented. The investigations included the collection of epidemiological data from affected farms and the testing of sera for antibodies to the virus. The authors report a mean morbidity rate of 50% and a mean case fatality rate of 0.3%. Of the infected cattle, 4% were affected by recumbency, the majority of these recovered (89%). The clinical signs observed in affected cattle were uniform throughout the region concerned. The features of the outbreak, obtained through field investigations, were considered in relation to the ecological and meteorological conditions which were prevalent at the time. The outbreak occurred during the summer months (May to October) in the central and eastern regions of Saudi Arabia, with the initial infection reported at the Al-Ahsa oasis. Farms which were subsequently affected were all reported to possess areas of stagnant water suitable for the reproduction of the vectors of the disease (Culicoides spp. and mosquitoes). To conclude, the authors discuss precautions to prevent future outbreaks of bovine ephemeral fever in Saudi Arabia.     

Analysing repeated measurements data: a practical comparison of methods.

A variety of methods are available for analysing repeated measurements data where the outcome is continuous. However, there is little information on how established methods, such as summary statistics and repeated measures analysis of variance (RMAOV), compare in practice with methods that have become available to applied statisticians more recently, such as marginal models (based on generalized estimating equation methodology) and multilevel models (that is, hierarchical random effects models). The aim of this paper is to exemplify the use of these methods, and directly compare their results by application to a clinical trial data set. The focus is on practical aspects rather than technical issues. The data considered were taken from a clinical trial of treatments for asthma in 240 children, in which a baseline and four post-randomization measurements of outcomes were taken. The simplicity of the method of summary statistics using the post-randomization mean of observations provided a useful initial analysis. However, fixed time effects or treatment-time interactions cannot be included in such an analysis, and choice of appropriate weighting when there is substantial missing data is problematic. RMAOV, marginal models and multilevel models generally provided similar estimates and standard errors for the treatment effects, although in one example with a relatively complex variance structure the marginal model produced less efficient estimates. Two advantages of multilevel models are that they provide direct estimates of variance components which are often of interest in their own right, and that they can be naturally extended to handle multivariate outcomes.     

Post-traumatic endophthalmitis: causative organisms and visual outcome

PURPOSE: Post-traumatic endophthalmitis makes up a distinct subset of intraocular infections. The purpose of the present study was to identify the causative organisms and record the visual outcome after infectious endophthalmitis in eyes with penetrating trauma. METHODS: We reviewed 18 consecutive cases of culture-positive endophthalmitis that developed after penetrating ocular trauma. All cases were treated with pars plana vitrectomy and intravenous and intraocular antibiotics. RESULTS: The 15 males and 3 females ranged in age from 4 to 43 years (mean 25.1 +/- 11 years). Nine (50%) had intraocular foreign bodies. A single species was isolated in 16 cases, and multiple organisms in two. Staphylococcus epidermidis and gram-negative organisms were the most frequent and were cultured either alone or in association with other organisms in respectively five (27.7%) and four cases (22.2%). Clostridium perfringens was isolated in three cases (16.6%). Bacillus was not found as a cause of endophthalmitis. Final visual acuity was better than 20/400 in eight cases (44%). In five cases (27.7%), the eye was saved but visual acuity was counting fingers. Two eyes (11%) had no light perception. The remaining three eyes (16.6%) were enucleated or eviscerated. Clostridium perfringens was isolated from two eyes and Aspergillus niger from one. Postoperative retinal detachment developed in four eyes, which were successfully operated. CONCLUSIONS: Organisms isolated in this series were similar to those in previous reports of post-traumatic endophthalmitis from other parts of the world, except that the frequency of Clostridium perfringens isolation was high and no Bacillus species were cultured. In view of its devastating outcome, post-traumatic endophthalmitis must be treated promptly with vitrectomy and intravitreal antibiotics.     

Basement membrane thickening in the placentae from diabetic women

A light microscopy study was carried out on 48 placentae. Seventeen placentae were obtained from non-diabetic mothers while the other 31 placentae were from both women with controlled diabetes and women who had an abnormality of the glucose tolerance test. All the women delivered at 38-40 weeks of gestation. Placentae from diabetic patients showed immaturity of the villi, hypertrophy of the capillaries and thickening of the basement membrane of the trophoblastic villi (3.2 +/- 0.35 microns) and the amniotic membrane (1.8 +/- 0.3 microns). Focal fibrinoid necrosis, an increase in the number of Hofbauer cells and dilatation of villi capillaries were also commonly observed in placentae from diabetic mothers, and the normal cuboidal cells lining the amniotic membrane tended to become tall columnar (17.6 +/- 6.3 microns) with distally located nuclei. Similar findings were observed in patients who had a potentially abnormal glucose tolerance test, which suggests the possibility of primary lesion in origin. Therefore, control of hyperglycemia may only partially prevent the development of placental abnormalities.     

The role of hyperthermia in regional alkylating agent chemotherapy.

The role of hyperthermia during regional alkylating agent chemotherapy is controversial. The aim of this study was to determine the exact contribution of hyperthermia to tumor response during isolated limb infusion with l-phenylalanine mustard. Rats bearing rodent fibrosarcoma on the hindlimb underwent isolated limb infusion with saline, saline plus heat, l-phenylalanine mustard, l-phenylalanine mustard under conditions of normothermia, or l-phenylalanine mustard plus hyperthermia. Heat was administered locally using an in-line hot water circulation loop. Treatment with l-phenylalanine mustard at a concentration of 15 or 50 micrograms/mL was ineffective at producing tumor growth delay (P = 0.24 and 0.41, respectively). Furthermore, thermal enhancement of l-phenylalanine mustard activity was not seen at 15 micrograms/mL. However, administration of high-dose l-phenylalanine mustard, 50 micrograms/mL, with increasing amounts of heat yielded increasing tumor growth delay, increased regressions, and decreased proliferative index. Although l-phenylalanine mustard infusion under normothermia yielded a tumor growth delay of 7.1 days, combination l-phenylalanine mustard + hyperthermia treatment produced tumor growth delay of 27.0 days (P < 0.01; with two of five animals showing a complete response). Four hours after isolated limb infusion, 50.9% of cells in tumor treated with l-phenylalanine mustard + hyperthermia experienced apoptosis, whereas only 18.1, 16, and 4.4% of cells underwent apoptosis after treatment with l-phenylalanine mustard, saline + hyperthermia, or saline. The mean concentration of l-phenylalanine mustard within tumor relative to perfusate following isolated limb infusion was found to be similar among all groups at 0.023, 0.025, and 0.032 in animals undergoing isolated limb infusion with l-phenylalanine mustard, l-phenylalanine mustard + normothermia, and l-phenylalanine mustard + hyperthermia, respectively. These data indicate a synergistic cytotoxic effect of l-phenylalanine mustard + hyperthermia in isolated limb infusion, which is not attributable to enhanced tumor drug uptake.     

Delayed effects of thallium in the rat brain: regional changes in lipid peroxidation and behavioral markers, but moderate alterations in antioxidants, after a single administration.

Thallium (Tl+) toxicity has been related with the generation of reactive oxygen species (ROS) and oxidative stress (OS) in the central nervous system. Since changes in endogenous antioxidant systems might contribute to acute Tl+-induced OS and neurotoxicity, in this study we measured the metal concentration and the levels of lipid peroxidation (LP) in different brain regions (hypothalamus (Ht); cerebellum (Ce); striatum (S); hippocampus (Hc) and frontal cortex (Cx)) in possible correlation with the content of reduced glutathione (GSH), the activities of glutathione peroxidase (GPx) and superoxide dismutase (SOD), and the animal performance in behavioral tests, all evaluated after a single administration of thallium acetate (8 or 16 mg/kg, i.p.) to rats. Seven days after Tl+ administration, the metal was homogeneously and dose-dependently accumulated in all regions evaluated. LP was increased in Ht, Ce and S, while GSH was depleted in S. Cu,Zn-SOD activity was also decreased in Ht and S. All these changes occurred with 16 mg/kg dose and at 7 days after treatment, but not at 1 or 3 days. In addition, Tl+-treated animals exhibited general hypokinesis, but no changes were observed in spatial learning. Our findings suggest that a delayed response of the brain to Tl+ may be the result of its residual levels. Also, despite the regional alterations produced by Tl+ in LP and the limited changes in endogenous antioxidants, there is a correlation between the Tl+-induced oxidative damage and the affected behavioral tasks, suggesting that, although still moderate, Tl+ evokes neurotoxic patterns under the experimental conditions tested.