Serum lipids and incidence of coronary heart disease. Findings from the Systolic Hypertension in the Elderly Program (SHEP)

BACKGROUND: The association of serum lipids with coronary heart disease has been studied extensively in middle-aged men and, to a lesser extent, in similar women. Less well defined are lipid variables predictive of CHD in individuals of age > or = 60 years. METHODS AND RESULTS: The Systolic Hypertension in the Elderly Program recruited 4736 persons (mean age, 72 years; 14% were black; and 43% were men). Mean systolic and diastolic blood pressures were 170 and 77 mm Hg, respectively. Baseline mean total cholesterol was 6.11 mmol/L (236 mg/dL); HDL cholesterol, 1.39 mmol/L (54 mg/dL); and non-HDL cholesterol, 4.72 mmol/L (182 mg/dL). Triglyceride levels were 1.62 mmol/L (144 mg/dL) for fasting participants and 1.78 mmol/L for the total group. LDL cholesterol, estimated in fasting samples with triglycerides of < 4.52 mmol/L, averaged 3.98 mmol/L (154 mg/dL). Mean follow-up was 4.5 years. In multivariate Cox regression analyses, baseline total, non-HDL, and LDL cholesterol levels and the ratios of total, non-HDL, and LDL to HDL cholesterol were significantly related to CHD incidence. HDL cholesterol and triglycerides were not significant in these analyses. In fasting participants with triglyceride levels of < 4.52 mmol/L, a 1.03 mmol/L (40 mg/dL) higher baseline total, non-HDL, or LDL cholesterol was associated with a 30% to 35% higher CHD event rate. CONCLUSIONS: The results of this study support the concept that serum lipids are CHD risk factors in older Americans.     

Contractile responses and structure of small bronchi isolated from rats after 20 months' exposure to ozone

Short-term exposure to high concentrations of ozone has been shown to increase airway responsiveness in normal humans and in all laboratory animal species studied to date. While our knowledge concerning the pulmonary effects of single exposures to ozone has increased rapidly over recent years, the effects of repeated exposures are less understood. The goal of the present study was to determine whether airway responsiveness is increased after near-lifetime exposure to ozone. Airway segments representing approximately eighth generation airways were isolated from Fischer 344 rats of both genders that had been exposed for 6 hr per day, 5 days per week for 20 months to 0, 0.12, 0.5, or 1.0 parts per million (ppm) ozone. Circumferential tension development was measured in isolated airways in response to bethanechol, acetylcholine, and electrical field stimulation. Responsiveness of the airways to the contractile stimuli was described by the effective dose or frequency that elicited half-maximum contraction (ED50) and the maximum response. Since ozone exposure is associated with remodeling of peripheral airways, smooth muscle area was determined and tension responses were normalized to the area measurements. Before normalization of tension data to smooth muscle area, neither the ED50 nor maximum response of small bronchi to the contractile stimuli was altered after chronic ozone exposure. Smooth muscle area was greater in airways isolated from animals that had been exposed to 0.5 ppm ozone. After accounting for smooth muscle area, maximum responses of the small bronchi isolated from male rats were significantly reduced after 0.12 and 0.5 ppm ozone. Although not significant statistically, a similar trend was observed in airways isolated from female rats. These results suggest that the increase in airway responsiveness associated with acute ozone exposure does not persist during near-lifetime exposure. Although the mechanism responsible for the adaptation to the effects of O3 on airway responsiveness is unknown, the results indicate that smooth muscle cell function was compromised by the chronic exposure. The mechanism(s) responsible for mediating this effect and the relevance of these results to humans remains to be determined.     

Efficacy of gloves in reducing blood volumes transferred during simulated needlestick injury

This study was designed to evaluate factors that affect blood volumes transferred to skin during simulated needlestick injuries in an in vitro paper prefilter model and an ex vivo porcine tissue model. The effect of needle type and size, penetration depth, and glove use on the volume of radiolabeled blood transferred was determined in each model. Blood volumes ranged from 0.47 +/- 0.26 microL (30-gauge needle, 0.5-cm depth, in vitro model) to 5.88 +/- 1.45 microL (18-gauge needle, 2.0-cm depth, in vitro model). Needle size and penetration depth were significantly associated with transfer volume. Glove material reduced the transferred blood volume by 46%-86% in both models. Transfer volumes were within the same order of magnitude for all conditions. Hence, virus titer in the source blood may be a better predictor of needlestick infectivity than is exposure volume. Regardless, gloves may exert some protective effect and should be worn whenever needles are handled.     

Chronic exposure of cultured bovine endothelial cells to oxidized LDL abolishes prostacyclin release

We investigated the effect of chronic exposure (3 days) with low-density lipoprotein (LDL) and oxidized (Ox)-LDL on the unstimulated and stimulated formation of prostacyclin (6-keto-prostaglandin [PG]F1 alpha) and total inositol phosphates (IPs) by cultured bovine aortic endothelial cells. Neither basal nor bradykinin-stimulated (1 to 10 nmol/L) formation of 6-keto-PGF1 alpha was affected by LDL, except at the highest concentration of bradykinin tested (100 nmol/L). In the presence of the antioxidants N-acetyl-L-cysteine (NAC, 10 mumol/L) or vitamin E (100 mumol/L), basal and bradykinin-stimulated formation of 6-keto-PGF1 alpha was potentiated by 20 micrograms protein/mL of LDL. Ox-LDL decreased unstimulated formation of the eicosanoid from 3.1 +/- 0.2 pg/micrograms protein in control cells to 1.6 +/- 0.1 and 0.5 +/- 0.1 pg/microgram protein after 3-day incubation with 5 and 20 micrograms protein/mL of Ox-LDL, respectively (P < .05). As in the basal state, Ox-LDL decreased bradykinin-induced 6-keto-PGF1 alpha formation. NAC or vitamin E did not influence Ox-LDL-induced endothelial cell changes in eicosanoid production. IPs formation by endothelial cells increased to a similar extent in the presence of 20 micrograms protein/mL of either LDL or Ox-LDL. However, no change was apparent in the bradykinin (10 mumol/L)-induced increase in total IPs formation after incubation with the lipoproteins. The data indicate that chronic exposure to Ox-LDL abolishes the production of prostacyclin by cultured endothelial cells. The oxidatively modified lipoprotein seems to more specifically affect the prostacyclin pathway.(ABSTRACT TRUNCATED AT 250 WORDS)     

Thyrotropin-receptor-mediated diseases: a paradigm for receptor autoimmunity

Autoantibodies to the thyrotropin receptor (TSHR) can act as thyrotropin agonists or antagonists, or can cause thyroid hypertrophy. Neither the autoantibody-binding sites on the TSHR nor the intracellular mechanisms by which the autoantibodies mediate their diverse functional effects are completely understood. This article reviews how cloning of the TSHR has contributed to our understanding of its structure and function, and has allowed induction of experimental autoimmunity to the TSHR.     

Late effects of radiotherapy in children

PURPOSE: To examine benzoporphyrin derivative angiography as a modality for studying photosensitizer biodistribution in experimental choroidal melanomas. METHODS: A liposomal preparation of benzoporphyrin derivative was used in this study. Digital benzoporphyrin derivative angiograms were performed in 10 rabbits (six for experimental choroidal melanomas, two for normal choroids, and two for irides) using a Topcon ImageNet H1024 digital imaging system, a Kodak Megaplus video camera, and a Topcon TRC-50-VT fundus camera. Only one eye from each rabbit was used. Filters specifically designed for benzoporphyrin derivative (peak absorption at 580 nm and peak emission at 695 nm) were used. Benzoporphyrin derivative (1 mg/kg) was injected into an ear vein while images of tumor, normal choroid, or iris were being obtained. Follow-up images were obtained during the first 3 hours and at 24 hours after injection. Fluorescence microscopy was performed in all 10 rabbits using 1 mg/kg of benzoporphyrin derivative. Tumor-bearing eyes were enucleated at the same time points that angiograms were performed, and the two sets of results were compared for maximum dye accumulation. RESULTS: Digital angiography demonstrated that maximal benzoporphyrin derivative fluorescence occurred in tumors 15 to 45 minutes after injection. Fluorescence photometry corroborated these results. CONCLUSION: Photosensitizer angiography is a valid modality for determining the optimum treatment time for photodynamic therapy.     

Pancreaticoduodenectomy for selected periampullary neuroendocrine tumors: fifty patients

BACKGROUND: Most resectable pancreatic or peripancreatic neuroendocrine tumors are treated by enucleation or distal pancreatectomy. A minority of tumors may require pancreaticoduodenectomy for complete tumor excision because of their large size, location, or lymph node involvement. METHODS: This study reviews the management of 50 patients treated by pancreaticoduodenectomy for periampullary neuroendocrine tumors between 1962 and 1996 at a single institution. RESULTS: There were 30 men and 20 women with a mean age of 52 +/- 2 years. Functional tumors were resected in 17 patients: insulinoma, seven tumors; gastrinoma, eight tumors; vipoma, one tumor; and glucagonoma, one tumor. Tumors were classified as malignant in 29 patients and benign in 21. The median intraoperative blood loss was 800 ml, and the median number of units of blood transfused was zero. The postoperative length of stay was 20 +/- 2 days. Postoperative morbidity included 11 patients (24%) with a pancreatic fistula and four patients (8%) with a biliary fistula. There was one in-hospital death (2%), in 1967. The actuarial survival rates at 2, 5, and 7 years are 81%, 73%, and 65%, respectively. Patients with benign tumors had a significantly improved 5-year survival rate (94%) compared with those with malignant tumors (61%; p = 0.03). CONCLUSIONS: Selected patients with periampullary neuroendocrine tumors can be managed successfully by pancreaticoduodenectomy, with low mortality and acceptable morbidity rates.     

The epidemiology of stroke: a focus on Rhode Island

Effects were studied of vincamin and tanakan in 68 patients with stage I, II and III discirculatory encephalopathy (as per WHO classification 1981). In 52% of the patients atherosclerosis of brain vessels was associated with arterial hypertension (group I), in 48 per cent venous discirculatory encephalopathy was diagnosable against the background of arterial hypertension (group IIA-20%) and arterial hypotension (group IIB-26%). Both tanakan and vincamin were found to be effective in group I patients; however, in stage III condition their effectiveness was no better than 42 and 15% respectively, which fact might be due to organic changes in the vascular wall. Tanakan appeared to be more beneficial in group II patients since venous dystonia is considered to be the main pathogenetic link in this context, and tanakan is known to improve the venous outflow from the cranial cavity. Almost in one-third of group IIB patients vincamin worsened general health status, especially so in stage III discirculatory encephalopathy, which fact may be related to peculiar effect of the drug on the arterial link of brain blood supply.