Fasting glucose cutoff point: where does the risk terminate? Tehran lipid and glucose study

The aim of this study is to determine safe fasting plasma glucose (FPG) levels. We included data on 5,960 individuals aged ≥20?years at baseline with at least one follow-up examination. Diabetes was ascertained in accordance with American Diabetes Association criteria, using standard 2-h post-challenge plasma glucose test. Multivariate restricted cubic splines Weibull regression was implemented for interval-censored survival data on incident diabetes. We used Harrell’s C statistic for discrimination, Nam-D’Agostino χ² for calibration, and Royston’s R ² for variations in the outcome explained by models. During a 6-year median follow-up, 369 incident cases of diabetes were ascertained. Family history of diabetes, systolic blood pressure, waist-to-height ratio, and triglyceride-to-high-density lipoprotein cholesterol ratio, independent of FPG and each other remained associated with incident diabetes. The cubic splines model achieved good calibration (χ²?=?12.1) and discrimination (C?=?0.828) and explained 75% of variation in the time until incident diabetes. A J-shaped FPG-diabetes relationship was observed. Descending arm of the dose–response relationship curve corresponded to increasing FPG levels up to 4.0?mmol?l^?1, where it started increasing. The risk of incident diabetes decreased with decreasing levels of FPG down to 4.0?mmol?l^?1, where the risk stopped decreasing. Multivariate-adjusted risk of incident diabetes was zero at FPG?=?5.05?mmol?l^?1. Although currently there is no firm evidence to show that early intervention among individuals with the elevated FPG levels could prevent or delay onset of diabetes, individuals with FPG levels below 5.05?mmol?l^?1 could be safely reassured about their near-term risk of developing incident diabetes and screened on a less frequent basis.     

Acquired immunodeficiency syndrome-associated non-Hodgkin's lymphomas and other malignancies in patients with hemophilia

Non-Hodgkin's lymphoma (NHL) is the most common human immunodeficiency virus (HIV)-associated malignancy in hemophiliacs. We studied the incidence and clinicopathologic features of NHL in 3,041 hemophiliacs followed at 18 US Hemophilia Centers between 1978 and 1989. Of the 1,295 (56.6%) who were HIV(+), 253 (19.5%) developed acquired immunodeficiency syndrome (AIDS), of whom 14 (5.5%) developed NHL. Three NHL occurred in HIV(-) hemophiliacs, for a 36.5-fold greater risk in HIV(+) than HIV(-) hemophiliacs (P < .001). The NHL incidence rate was 29-fold greater than in the US population by Surveillance, Epidemiology, and End Results (SEER) estimates (P < .001). Between 0 and 4 lymphomas have been observed per year between 1978 and 1989. At presentation 13 (92.9%) of the HIV(+) NHL were extranodal. Ten were stage IV, 1 stage II, and 3 stage IE. Ten (71.4%) were high-grade, 3 (21.4%) intermediate-grade, and 1 (7.1%) was a low-grade B-cell lymphoma. Epstein-Barr virus (EBV) DNA was detected in 36% by in situ hybridization, including one central nervous system (CNS) lymphoma. The mean CD4 cell count at NHL diagnosis was 64/mm3, the mean latency from initial HIV infection was estimated to be 59 months, and the median survival was 7 months. The incidence of basal cell carcinoma in HIV(+) hemophiliacs was 18.3-fold greater than in HIV(-) hemophiliacs (P < .001) and 11.4-fold greater than in the US population (P < .001). In conclusion, incidence rates of NHL and basal cell carcinoma in HIV(+) hemophiliacs are significantly increased over rates in HIV(-) hemophiliacs and over rates in the US population. Clinicopathologic presentation of NHL in HIV(+) hemophiliacs is similar to that in HIV(+) homosexual men.     

Cytomegalovirus Localization in Atherosclerotic Plaques is Associated with Acute Coronary Syndromes: Report of 105 Patients

It has been shown that cytomegalovirus (CMV) is present in coronary atherosclerotic plaques, but the clinical rele-vance of this presence remains to be elucidated. In this study we sought to examine CMV infection in atherosclerosis patients defined by different methods and to identify the clinical significance of CMV replication in the atherosclerotic plaques. The study included 105 consecutive patients who were admitted to our department and underwent coronary artery bypass grafting (CABG) surgical interventions. Coronary atherosclerotic specimens as well as 53 specimens from the mamillary artery of these same patients were analyzed. Enzyme-linked immunosorbent assay (ELISA) and poly-merase chain reaction (PCR) methods were used for evaluations. The CMV PCR test result was positive for 28 (26.7%) of patients with coronary artery atherosclerosis. After adjusting for other risk factors, coronary artery disease patients with a history of acute coronary syndrome were more likely to be positive for CMV PCR test (P=0.027; odds ratio: 4.2; 95% CI: 1.18-15.0). They were also more likely to have a positive family history for cardiovascular diseases (CVD). This study confirms previous evidence about the replication of CMV virus in the atherosclerotic plaques of coronary arteries and brings clinical significance to this observation by showing a higher prevalence of acute coronary syndromes in those patients with CMV-infected plaques. Our study also suggests a familial vulnerability to CMV replication in the coronary artery walls.     

Traumatic Coronary Artery Fistula Closure with Stent Graft

We present a rare case of a symptomatic acquired large coronary fistula and aneurysm secondary to chest trauma that was successfully closed using stent graft. This case is followed by review of the literature.     

Stimulation of eosinophil production in vitro by eosinophilopoietin and spleen-cell-derived eosinophil growth-stimulating factor

Eosinophilopoietin (EPP) was previously characterized by the ability to stimulate eosinophil production in vivo, but these studies could not ascertain whether EPP had a direct effect on the bone marrow or acted indirectly by causing release of eosinophilopoietic activity by other tissues. The present studies demonstrate that EPP stimulates eosinophil growth in liquid culture of mouse bone marrow in vitro. The timing of stimulation by EPP in vivo and in vitro were parallel, with maximal eosinophil growth after 48 hr. Moreover, EPP appears similar to, and possible identical with, the eosinophil growth-stimulating substance (EO-GSF) released by antigenic stimulation of immune nonadherent spleen cells. Both EPP and EO-GSF are of low molecular weight, both produce stimulation of eosinophil growth with identical kinetics, and both produced similar dose-response curves in the liquid culture system.     

Eosinophils stimulate fibroblast DNA synthesis

Fibrosis complicates a number of chronic inflammatory diseases and occurs in some conditions following chronic hypereosinophilic syndromes. We assessed whether eosinophils might be a source of fibrogenic factors. Extracts of human and guinea pig cell populations enriched for eosinophils contained substances that stimulated tritiated thymidine incorporation by human fibroblasts. Supernatants derived from resting eosinophils and extracts prepared from eosinophil granules also contained fibrogenic factors. Our findings demonstrate a new potential role for eosinophils and suggest a causal relationship between tissue eosinophilia and scar formation in certain parasitic conditions.     

Bench-to-bedside review: Diaphragm muscle function in disuse and acute high-dose corticosteroid treatment

Critically ill patients may require mechanical ventilatory support and short-term high-dose corticosteroid to treat some specific underlying disease processes. Diaphragm muscle inactivity induced by controlled mechanical ventilation produces dramatic alterations in diaphragm muscle structure and significant losses in function. Although the exact mechanisms responsible for losses in diaphragm muscle function are still unknown, recent studies have highlighted the importance of proteolysis and oxidative stress. In experimental animals, short-term strategies that maintain partial diaphragm muscle neuromechanical activation mitigate diaphragmatic force loss. In animal models, studies on the influence of combined controlled mechanical ventilation and short-term high-dose methylprednisolone have given inconsistent results in regard to the effects on diaphragm muscle function. In the critically ill patient, further research is needed to establish the prevalence and mechanisms of ventilator-induced diaphragm muscle dysfunction, and the possible interaction between mechanical ventilation and the administration of high-dose corticosteroid. Until then, in caring for these patients, it is imperative to allow partial activation of the diaphragm, and to administer the lowest dose of corticosteroid for the shortest duration possible.     

Body Surface Mapping and Nontraditional ECG Leads in Patients with Wolff-Parkinson-White Syndrome

A method of ECG mapping from 90 points on the chest surface is described in 41 male and 17 female patients, aged 6 to 59 years. All also underwent invasive electrophysiological investigation and intraoperative epicardial mapping. Fifty-two patients had one, three patients two, and one patient had three anomalous accessory pathways. Two patients had nodoventricular tracts (Mahaim fibers). We distinguished seven zones along the atrioventricular groove (AVG) to compare the data derived from epicardial, endocardial, and body surface mapping. A microcomputer was used for the analysis of all ECGs to construct and analyze the isopotential maps. The criterion for localization of the anomalous accessory pathways was determined after analysis of the data from all 58 patients. The localization criterion was the appearance of a minimal deflection (-0.09 +/- 0.03 mV) on the surface isopotential maps within the first 0.28 msec of the QRS complex. This criterion for localization of anomalous accessory pathways from the chest surface was proposed on the basis of comparison of data from selective coronary angiography, the ventriculogram, and the chest X ray i.e., radiographic-topographic-anatomical data. In 20 patients, 10-20 nontraditional ECG leads were recorded from the chest to reflect the atrioventricular groove. The number of nontraditional ECG leads depended on patient age, weight, and height. Localization of the accessory pathway in one of the seven zones was established by the earliest delta wave and its maximum deviation. It was possible to localize the anomalous accessory pathway and to suspect multiple pathways in 95% of cases using nontraditional ECG leads and the listed criteria.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pregnancy augments nitric oxide-dependent dilator response to acetylcholine in the human uterine artery

The influence of pregnancy on the dilator effects of acetylcholine in the isolated human uterine artery was investigated. Acetylcholine (0.1 nM to 0.1 microM) produced concentration- and endothelium-dependent relaxation of norepinephrine (3 microM)-induced contraction. The relaxation was greater in arteries from pregnant patients (P arteries) than from non-pregnant patients (NP arteries). The maximal relaxation was 53.5+/-3.4% (n=21) in P arteries and 23.5+/-2.5% (n=35) in NP arteries. In both P and NP arteries the cholinergic relaxation was increased in the presence of superoxide dismutase and greatly reduced in the presence of the nitric oxide synthase inhibitors, NG-mono-methyl L-arginine (L-NMMA) and L-nitro-arginine-methylester (L-NAME). The effect of these nitric oxide synthase inhibitors was reversed by L- arginine. We conclude that pregnancy enhances acetylcholine-induced nitric oxide synthesis and release in the human uterine artery.