Remarkably large,benign esophageal tumor

Digestive Diseases and Sciences - A patient with a leiomyoma of the esophagus is reported because it reached extraordinary size before becoming symptomatic and caused some difficulty in diagnosis...     

The association between lipid levels and the risks of incident myocardial infarction, stroke, and total mortality: The Cardiovascular Health Study

OBJECTIVES: To assess the association between lipid levels and cardiovascular events in older adults. DESIGN: A prospective population-based study. SETTING: Four field centers in U.S. communities. PARTICIPANTS: A total of 5,201 adults aged 65 and older living in U.S. communities, plus a recruitment of 687 African Americans 3 years later. MEASUREMENTS: Fasting lipid measures included low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), total cholesterol, and triglycerides. RESULTS: At baseline, 1,954 men and 2,931 women were at risk for an incident myocardial infarction (MI) or stroke. During an average 7.5-year follow-up, 436 subjects had a coronary event, 332 had an ischemic stroke, 104 a hemorrhagic stroke, and 1,096 died. After adjustment, lipid measures were not major predictors of the outcomes of MI, ischemic stroke, hemorrhagic stroke, and total mortality. For total cholesterol and LDL-C, the associations with MI and ischemic stroke were only marginally significant. HDL-C was inversely associated with MI risk (hazard ratio=0.85 per standard deviation of 15.7 mg/dL, 95% confidence interval=0.76-0.96). For the outcome of ischemic stroke, high levels of HDL-C were associated with a decreased risk in men but not women. Lipid measures were generally only weakly associated with the risks of hemorrhagic stroke or total mortality. CONCLUSION: In this population-based study of older adults, most lipid measures were weakly associated with cardiovascular events. The association between low HDL-C and increased MI risk was nonetheless strong and consistent.     

Malabsorption syndrome occurring in the course of disseminated histoplasmosis: case report and review of gastrointestinal histoplasmosis.

Histoplasmosis is caused by the dimorphic fungus, Histoplasma capsulatum. The disease spectrum varies from a mild respiratory infection to a lethal, disseminated form. Involvement of any part of the gastrointestinal tract may occur with the disseminated form, and symptoms reflect that portion involved. A case of malabsorption syndrome occurring during the course of disseminated histoplasmosis is reported, and the literature of gastrointestinal histoplasmosis is reviewed.     

Problems with gait and posture in neuropathic patients with insulin-dependent diabetes mellitus.

Peripheral neuropathy secondary to diabetes mellitus is believed to cause postural instability and uncoordinated gait, although this is not well documented. Two groups of patients from the Pittsburgh Epidemiology of Diabetes Complications Study, matched for age and duration of Type 1 diabetes, but with significantly different vibratory sensation thresholds as determined by Vibratron II testing, were therefore surveyed. The mean ages were 32.9 and 31.9 years and durations of diabetes were 22.0 and 18.8 years for the neuropathic and control groups, respectively. Patients provided details of fall injuries, and perception of safety during standing and walking. Multiple linear and logistic regression models were used to account for potentially associated variables such as gender, retinopathy, and duration of diabetes. The neuropathic group had adjusted odds ratios for reported injuries during gait of 15.0 relative to the control group (95% confidence intervals 1.04-216.59). The neuropathic group also reported significantly lower scores (less safe, p = 0.004) than the control group on perceived safety in unusual conditions. It is concluded that peripheral neuropathy has an effect on gait and posture which is clinically significant and that this effect merits further biomechanical study in neuropathic patients.     

Effects of verapamil on the extracellular K+ rise during myocardial ischaemia in dogs

The effects of verapamil on the [K+]o rise produced by myocardial ischaemia were assessed in 26 open chest mongrel dogs. Ischaemia was produced by intermittent occlusion of the LAD artery (15 dogs) or by reduction of flow of the cannulated LAD (11 dogs). Specially constructed valinomycin K+ sensitive electrodes were inserted into the mid myocardium in the central zone of ischaemia (CZ); in the margin (MZ) and in the nonischaemic zone (NZ). Occlusion of the coronary artery under controlled conditions produced significant [K+]o rise, greater in the CZ than in the MZ. During the infusion of verapamil the ischaemic [K+]o rise was substantially reduced in both zones. During controlled 75% reduction of coronary flow the [K+]o reached a plateau that remained stable until reperfusion was re-established. During verapamil infusion, the plateau showed a steady decline, both in the CZ and in the MZ. The changes in [K+]o produced by verapamil, during myocardial ischaemia are probably due to: coronary dilatation of the marginal arteries and+or to a reduction of the late cellular K+ conductance due to a decrease in the intracellular Ca2+, produced by verapamil.     

Familial and sporadic insulin-dependent diabetes: evidence for heterogeneous etiologies?

Heterogeneity within insulin-dependent diabetes mellitus (IDDM) has been hypothesized, but few studies have focused on differences which may exist between familial and sporadic IDDM cases. Presenting characteristics for 330 white, newly diagnosed IDDM cases were evaluated. Familial cases were older (10.2 +/- 5.1 years vs 7.9 +/- 4.2 years, P = 0.010) and had, on average, less severe metabolic disturbances at presentation, as demonstrated by lower mean hemoglobin A1 (12.6 +/- 2.4% vs 14.4 +/- 2.6%, P = 0.001) and mean insulin dose at discharge (0.62 +/- 0.35 U/kg/day vs 0.85 +/- 0.29 U/kg/day, P less than 0.001), and higher mean plasma bicarbonate concentrations (19.3 +/- 3.9 mmol/l vs 15.8 +/- 5.9 mmol/l, P = 0.023) and mean plasma C-peptide levels (0.35 +/- 0.36 pmol/ml vs 0.14 +/- 0.15 pmol/ml, P less than 0.001). Further analyses on a subset of IDDM cases (n = 100) indicated that initial differences in metabolic indices observed at diagnosis were no longer apparent at one-year post-diagnosis. These results suggest that the etiology of familial and sporadic IDDM is similar and that the less severe presentation observed at diagnosis in the familial cases may be due to earlier identification of the disease, reflecting increased parental knowledge of diabetic symptoms and/or frequent testing for diabetes.     

Oxidative Stress and Response in Relation to Coronary Artery Disease in Type 1 Diabetes

OBJECTIVE

Although oxidative stress (OxS) is thought to contribute to atherosclerosis and coronary artery disease (CAD), little is known about the variability in an individual’s ability to respond to OxS. Therefore, we assessed potential indices of response to OxS and evaluated whether they modify the association between OxS and CAD.

RESEARCH DESIGN AND METHODS

We evaluated plasma α- and γ-tocopherol per unit cholesterol (potential response markers); urinary 15-isoprostane F_2t per milligram creatinine (isoprostane [IsoP], a potential stress marker); and the α-tocopherol-to-IsoP ratio (as a measure of response to stress), measured three times during 20 years of follow-up, in relation to CAD incidence in a cohort with childhood-onset type 1 diabetes (n = 658; mean age at baseline, 28 years; duration of diabetes, 19 years). Participants with three samples (blood and either 24-h or overnight urine) available before the onset of CAD or the end of follow-up (n = 356) were selected for study.

RESULTS

In multivariable mixed models, α-tocopherol over time was inversely associated with CAD (β = −0.27; P = 0.02), whereas a direct association was observed for IsoP (β = 0.0008; P = 0.06). Moreover, the α-tocopherol-to-IsoP ratio was strongly and inversely related to CAD incidence (β = −0.72; P = 0.003), whereas in a separate model including α-tocopherol and IsoP, both biomarkers maintained statistical significance. No association was observed for γ-tocopherol (β = −0.22; P = 0.54).

CONCLUSIONS

These data suggest that a greater potential capability (α-tocopherol) to respond to OxS (urinary IsoP) relates to CAD incidence.Although the generation of reactive oxygen species is a natural and essential feature of human physiology, free radicals can also be cytotoxic, attacking and altering the structure and function of lipids, proteins, and nucleic acids, thereby compromising normal cellular function (1). To maintain normal cellular physiology, a balance is required between the pro- and antioxidant forces, while a relative excess production of free radicals, and the resulting oxidative stress (OxS), has been implicated in both the development as well as the progression of diabetes-associated complications (2). Unfortunately, the lack of sensitivity, specificity, or both in the methodologies commonly used to assess OxS in vivo, the requirement for invasive methods, and/or the influence of external factors on measurements obtained have prohibited definitive conclusions in human studies (3). Furthermore, little effort has been made to quantify response potentials (i.e., antioxidant defenses) relative to the stress encountered by individuals.Antioxidant vitamins comprise one of the defense mechanisms available to living systems to counteract the damaging effects of excess free radical production (4). However, despite early encouraging findings from prospective cohort studies, clinical trials of antioxidant supplementation for the prevention of cardiovascular disease have generally provided null results (5). Our own observation of a protective effect of plasma concentrations of α-tocopherol on the incidence of coronary artery disease (CAD) among individuals with type 1 diabetes also was puzzling because it seemed to be confined to those using antioxidant vitamin supplements but occurred at concentrations similar to those of nonsupplement users (6).More recent discoveries, such as the ability to measure isoprostanes, may help to better quantify the level of OxS and permit analyses related to antioxidative defenses in humans. Indeed, isoprostanes are currently considered the gold standard biomarker of OxS and lipid peroxidation in vivo (3) and may provide a better opportunity to evaluate this important lipid peroxidation pathway in the pathophysiology of vascular diseases. Thus, we aimed to revisit the OxS hypothesis to evaluate whether the degree to which an individual with type 1 diabetes is potentially able to respond to OxS (e.g., plasma levels of antioxidant vitamins) is associated with cardiovascular risk and whether this varies with levels of such stress (e.g., urinary isoprostanes).     

Non-aspirin non-steroidal anti-inflammatory drugs in colorectal cancer: a review of clinical studies

Colorectal cancer (CRC) chemoprevention is an area of interest. Non-steroidal anti-inflammatory drugs (NSAIDs) are anti-inflammatory agents which have been identified as cancer chemoprevention agents given that inflammation is thought to contribute to tumorigenesis. Most studies have demonstrated that the NSAID, aspirin, plays a beneficial role in the prevention of CRC and colonic adenomas. Non-aspirin NSAIDs (NA-NSAIDs) have also been studied in CRC chemoprevention. There is increasing literature around their role in pre-cancerous polyp prevention and in decreasing CRC incidence and CRC-related outcomes in certain high-risk subgroups. However, the use of NA-NSAIDs may be accompanied by increased risks of toxicity. Further studies are required to establish the associations between concurrent aspirin and NA-NSAID use, and CRC-related outcomes.Subject terms: Colorectal cancer, Cancer prevention     

Comparison of a supplemented Rose Questionnaire to exercise thallium testing in men and women

The Rose Questionnaire has had high specificity and variable sensitivity when compared to physician identification of the symptom complex of angina pectoris. We assessed the accuracy of a supplemented Rose Questionnaire in a series of 198 patients by comparing the Questionnaire to exercise thallium test evidence of coronary artery disease. The Rose diagnosis of angina had 26% sensitivity, 79% specificity, 42% positive predictive value, and 65% negative predictive value. The Rose diagnosis of myocardial infarction had 26% sensitivity and 90% specificity. The Rose diagnosis of angina or infarction yielded a sensitivity of 44%, specificity of 72%, positive predictive value of 67%, and negative predictive value of 50%. Supplemental questions designed to identify atypical ischemic pain led to increased sensitivity of up to 68% that was offset by decreased specificity. While the Questionnaire's sensitivity for coronary disease was greater for women than men (57 vs 40%), the overall accuracy was the same because specificity was lower (63 vs 80%).