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Biomedical subjects

D Ellis

Publications and source records attributed to D Ellis.

At least 271 records · Page 15Linked to original sources

Spontaneous whole blood platelet aggregation, hematological variables and complications in insulin-dependent diabetes mellitus: the Pittsburgh Epidemiology of Diabetes Complications Study.

The role of platelet aggregation in the pathogenesis of diabetes complications remains unclear despite a number of reports suggesting associations in univariate analyses. The Pittsburgh Epidemiology of Diabetes Complications Study is a prospective study initiated in 1985 to determine risk factors for the development of complications in insulin-dependent diabetes mellitus (IDDM). This report focuses on the cross-sectional correlation between platelet count and aggregation and IDDM complications, in 563 participants aged 18 years and older seen at baseline. Spontaneous whole blood platelet aggregation (SWBPA) and other hematological variables [hematocrit, total platelet count (TPC), red blood cell count (RBC), fibrinogen and white blood cell count (WBC)] were evaluated as risk factors for IDDM complications (nephropathy, neuropathy, and retinopathy) in the baseline cross-sectional data of the Pittsburgh Epidemiology of Diabetes Complications Study. SWBPA was determined by a method based on the percentage fall in platelet count after shaking a fresh citrated blood sample kept at 37 degrees C. Subjects with chronic aspirin use or on dialysis were excluded from analysis. An increased TPC was observed in subjects with overt nephropathy (291.4 +/- 65.1 versus 261.2 +/- 64.9, p less than 0.001) compared with subjects without nephropathy. Similar results were found for proliferative retinopathy. The association with nephropathy (but not with retinopathy) persisted in multivariate analyses.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Cardiovascular autonomic neuropathy (expiration and inspiration ratio) in type 1 diabetes. Incidence and predictors.

The pathogenesis of diabetic neuropathy is poorly understood. In this prospective study, we investigated the incidence rate and potential predictors for cardiovascular autonomic neuropathy (CAN) in a cohort of childhood-onset type 1 diabetic patients. Subjects from the Epidemiology of Diabetes Complications Study were examined at baseline and then biennially. CAN was diagnosed by abnormal (</=1. 1) expiration/inspiration ratio during deep breathing. During the 4. 7-year mean follow-up period, CAN developed in 104 patients from the 373 subjects who were free of CAN at baseline and provided follow-up data, an incidence-density of 5.9 cases/100 person-years. Cox proportional hazard modeling showed age (relative risk [RR]=2.15, p=0.0001), HbA1 (RR=1.50, p=0.0002) and nephropathy (albumin excretion >200 ug/min) (RR=2.46, p=0.0001) to be significant independent predictors. Hypertension was, however, predictive if nephropathy was not included in the model. We conclude that beyond age and poor glycemic control, nephropathy is a significant risk factor for CAN and this association may explain some of the increased mortality seen in CAN.

Adult↗

Lipid modulation in insulin-dependent diabetes mellitus: effect on microvascular outcomes.

Although hyperlipidemia is associated with the development of diabetes complications, the effect of lipid reduction on microvascular complications is unknown. We initiated a 2-year, randomized, double-blinded placebo-controlled pilot trial of simvastatin/diet vs. diet alone in Type 1 diabetic patients without overt nephropathy. Thirty-nine patients with LDL cholesterol 100-160 mg/dl, >10 year duration of diabetes and an albumin excretion rate (AER) <200 microg/min were recruited for study. The primary end-point was change in AER. Secondary end-points were change in ankle-brachial index, progression of retinopathy status, change in vibratory threshold, and development of new clinical neuropathy. Nineteen patients were treated with simvastatin and twenty with placebo. However, because of the lowering of drug initiation levels by the American Diabetes Association, the trial was terminated early with 2 subjects reaching 2 years, 17 reaching 18 months, 36 reaching 1 year, and all 6 months. Simvastatin significantly reduced total cholesterol (mean on treatment 173.4 vs. 191.4, P=.020) and LDL cholesterol (mean on treatment 105.0 vs. 127.7, P<.001). Simvastatin therapy was associated with a slower rise in AER compared to placebo, though the result was not statistically significant (median rate of change/month 0.004 vs. 0.029). There was a trend towards slower progression of neuropathy as measured by vibratory threshold (median change at 1 year 0.03 simvastatin vs. 0.94, P=.07). There was no difference in change in ankle-brachial index, clinical neuropathy status, or retinopathy status. In conclusion, treatment with simvastatin may have a beneficial effect on early nephropathy and diabetic neuropathy, justifying a fully powered trial. However, this would be difficult under current treatment guidelines.

Adult↗

Do tissue plasminogen activator-plasminogen activator inhibitor-1 complexes relate to the complications of insulin-dependent diabetes mellitus? Pittsburgh Epidemiology of Diabetes Complications Study.

The purpose of this study was to examine the potential relationship of tissue plasminogen activator-plasminogen activator inhibitor-1 (tPA-PAI-1) complexes and diabetic complications in individuals with insulin-dependent diabetes mellitus (IDDM). To address this issue, data from the third follow-up visit of participants in the Epidemiology of Diabetes Complications (EDC) study were examined. There were 454 participants, aged 32 +/- 8 years, with duration of IDDM of 23 +/- 8 years. Higher levels of tPA-PAI-1 complexes were seen for both men and women with IDDM complications. Specifically, statistically significant differences were seen in men with neuropathy (1.81 +/- 0.9 versus 1.42 +/- 0.8 ng/mL, p < 0.01), microalbuminuria (1.77 +/- 1.1 versus 1.35 +/- 0.6 ng/mL, p < 0.01), retinopathy (1.67 +/- 0.9 versus 1.43 +/- 0.8 ng/mL, p < 0.05), and lower extremity arterial disease (1.93 +/- 0.7 versus 1.50 +/- 0.9 ng/mL, p < 0.05) versus men without the particular complication. In women, higher complex levels were shown for those with retinopathy (1.51 +/- 0.8 versus 1.29 +/- 1.1 ng/mL, p < 0.01). Potential mechanisms for the relationship of higher complex levels and diabetic complications include an altered fibrinolytic response and/or insulin resistance. Because the results are cross sectional, it cannot be established whether the higher concentration of complexes is a result of the presence of complications or are antecedent. Prospective follow-up will be required to determine if tPA-PAI-1 complexes are predictive of the development of IDDM complications.

Adult↗

A thyromimetic that decreases plasma cholesterol levels without increasing cardiac activity.

A number of agents that mimic the ability of the thyroid hormone, T3, to decrease plasma cholesterol levels are described; one is as effective as T3 at reducing cholesterol levels and stimulating liver function, but has very little effect on cardiac function and is thus less likely to be toxic. The agent may be useful in the treatment of atherosclerosis.

Animals↗

Molecular analysis in the diagnosis of pediatric lymphomas.

Thirty-five pediatric lymphomas were categorized as either Burkitt's lymphoma (BL), lymphoblastic lymphoma (LL), or large cell anaplastic lymphoma (LCAL) by histological and immunophenotypic methods. They were further characterized by molecular analysis of their antigen receptor genes. Southern blot (SB) and polymerase chain reaction (PCR) techniques were compared in the detection of immunogloblin heavy chain gene (IgH) rearrangement. T cell receptor beta (TCR beta) rearrangements were analyzed by SB and TCR gamma gene rearrangements by PCR. The PCR method of IgH and TCR gamma gene analysis was preferred to the SB methods, because there were fewer equivocal results in IgH gene analysis, TCR gamma rearrangement was more frequently detected than TCR beta in both lymphoblastic and large cell anaplastic lymphomas, and the PCR technique was more rapid, required less DNA, and could be used with archival material. In addition, analysis of IgH gene rearrangement by PCR was more specific for assessing B cell lineage. Although most of the molecular data were easily interpreted, occasional ambiguous results were seen due to genetic events other than antigen receptor gene rearrangement affecting the genetic analysis. Thus, it is imperative to interpret these genetic data in the context of adequate morphological and immunophenotypic analysis.

Blotting, Southern↗

Methods of assessment for use with the visually and mentally handicapped: a selective review.

Literature published during the last 15 years and concerning assessment techniques applicable to the visually and mentally handicapped is reviewed. Aspects of assessment considered include professional organisation of health teams, electrophysiological measures, psychometric methods and some experimental investigations. The value of more reliable behavioural observation relevant to the client's future practical training needs is stressed.

Child↗

Fluconazole in the treatment of pulmonary zygomycosis.

Pulmonary zygomycosis is an aggressive, often terminal infection that may be found in patients who are immunocompromised as a result of cytotoxic chemotherapy. Conventional treatment is by surgical debridement augmented with high-dose intravenous amphotericin B, but even with such treatment the course is usually fulminant with a high mortality rate. Recent work has suggested that the new antifungal triazole, fluconazole, may be of benefit in treating zygomycete infection. The case of a 15-year-old boy who developed pulmonary zygomycosis while on chemotherapy for acute lymphoblastic leukaemia, and who survived for 11 months with oral fluconazole therapy alone, is supportive of this proposal.

Antifungal Agents↗

Positive-outcome bias: comparison of emergency medicine and general medicine literatures.

OBJECTIVE: The existence of positive-outcome bias in the medical literature is well established. Positive-outcome bias in two emergency medicine journals was compared with that found in two general medicine journals. METHODS: Published original contributions from Annals of Emergency Medicine, American Journal of Emergency Medicine, JAMA, and New England Journal of Medicine were reviewed. Articles were categorized as demonstrating a positive or negative outcome or showing no difference using new criteria. Descriptive articles were excluded. RESULTS: Of 700 articles reviewed, 177 emergency medicine and 211 general medicine articles met the study criteria. The emergency medicine journals had 142 articles (80%) with positive outcomes, 27 (15%) with negative outcomes, and 8 (5%) with no difference. The general medicine journals had 169 articles (80%) with positive outcomes, 33 (16%) with negative outcomes, and 9 (4%) with no difference. There was no significant difference between journal groups (chi-square; p = 0.99). The power of the study was 0.80 to detect a difference of 15% between groups with alpha set at 0.05. CONCLUSION: There was no significant difference in the proportions of positive-outcome studies published in this sample of the emergency medicine literature compared with the general medicine literature. The potential impact of positive-outcome bias and methods of dealing with the problem are reviewed.

Emergency Medicine↗

Cardiovascular disease and arterial calcification in insulin-dependent diabetes mellitus: interrelations and risk factor profiles. Pittsburgh Epidemiology of Diabetes Complications Study-V.

Cardiovascular disease is a frequent complication of insulin-dependent diabetes mellitus (IDDM), but the prevalence, interrelations, and risk factors of its principal components (coronary, cerebrovascular, and lower-extremity arterial disease) and of medial arterial wall calcification are not well understood. To address these issues, data from the Epidemiology of Diabetes Complications Study (n = 657) baseline examination were examined. The term coronary heart disease (CHD) was applied to those with myocardial infarction or angina, whereas lower-extremity arterial disease (LEAD) was applied to those who had undergone amputation of a lower limb or who had an ankle to arm blood pressure ratio less than 0.8 at rest or after exercise. Calcification of the lower-extremity arteries was considered to be present if ankle pressure was more than 100 mm Hg higher than brachial pressure. Although the prevalence of CHD was low, LEAD was significantly more common in women than in men (p less than 0.01), whereas calcification was more frequent in men than in women (p less than 0.01). Ten percent of those with LEAD also had CHD, and 8% with LEAD had calcification. Modeling of potential risk factors (e.g., diabetes duration and glycosylated hemoglobin) revealed that duration, female gender, fibrinogen, low density lipoprotein cholesterol, high density lipoprotein cholesterol, and high density lipoprotein cholesterol to apolipoprotein A-I ratio were independent predictors of LEAD, whereas for CHD only, diabetes duration and hypertension contributed to CHD. Calcification revealed a mixed pattern, with duration, hypertension, and triglyceride to apolipoprotein A-I ratio being the statistically significant associated factors. The results suggest that although LEAD, CHD, and calcification often coexist, their risk factor profiles differ.

Adult↗

Fluid and electrolyte balance during a cool weather marathon.

Changes in blood, serum, and urine parameters that are usually associated with fluid and electrolyte balance were studied in 45 volunteers who ran the 1987 Pittsburgh Marathon. There were 39 males and 6 females. The mean age was 39.3 years. Their mean fluid intake was 1650 cc and the mean finishing time was 4 hours and 1 minute. The race was run in the rain with a temperature of 46 degrees F. When the prerace and postrace values of the runners were compared, significant increases were noted in the serum sodium, potassium, blood urea nitrogen (BUN), creatinine, uric acid, creatine phosphokinase (CPK), protein, plasma renin, vasopressin, and urinary potassium. Significant decreases were found in weight, blood pressure, and urinary sodium. No significant differences were noted in serum chloride, serum glucose, and hemoglobin/hematocrit. The mean weight loss of 1.9 kg was less than weight losses reported in marathons run under warmer conditions.

Adult↗

Contribution of diabetes duration before puberty to development of microvascular complications in IDDM subjects.

The contribution of diabetes duration, both pre- and postpuberty, to the development of microvascular complications and mortality in diabetic subjects was investigated in three study populations from the Children's Hospital of Pittsburgh Insulin-Dependent Diabetes Mellitus (IDDM) Registry. Life-table analyses by total and postpubertal IDDM duration were used to evaluate differences in the prevalence of microvascular complications and diabetes-related mortality in subjects diagnosed before and during puberty, as defined by an age at IDDM onset marker of 11 yr for girls and 12 yr for boys. The prevalence of retinopathy and overt nephropathy in 552 White adult diabetic subjects (population 1, mean IDDM duration 20.8 yr was significantly greater in subjects diagnosed during puberty compared with those diagnosed before puberty. However, similar analyses by postpubertal duration showed no difference in microvascular complication prevalence between the two groups. These findings did not appear to be due to a confounding effect of age. Additional analyses of 239 adolescent diabetic subjects (population 2, mean duration 8.3 yr) revealed the same trend for the prevalence of retinopathy. Finally, results concerning the risk of diabetes-related mortality in a cohort of 1582 subjects (population 3, mean duration 12.9 yr) indicated that postpubertal duration of IDDM may be a more accurate determinant of the development of microvascular complications and diabetes-related mortality than total duration, and it is suggested that the contribution of the prepubertal years of diabetes to long-term prognosis may be minimal.

Adolescent↗

Diabetes complications and glycemic control. The Pittsburgh Prospective Insulin-Dependent Diabetes Cohort Study Status Report after 5 yr of IDDM.

The relationship between glycemic control and complications of insulin-dependent diabetes mellitus (IDDM) remains controversial. With the use of glycosylated hemoglobin (HbA1) to assess glycemic control from diagnosis onward, the Pittsburgh Prospective Insulin-Dependent Diabetes Mellitus Cohort Study prospectively evaluated 80 new cases of IDDM diagnosed at Children's Hospital of Pittsburgh. This study presents findings in 62 patients at 5 yr postdiagnosis. Only 7 patients, all girls, had any retinopathy (microaneurysms). These subjects had an elevated 5-yr mean HbA1 compared to those with no retinopathy (13.0 vs. 11.7%; P less than .05). Six female subjects who had an elevated albumin excretion rate (AER; greater than or equal to 20 micrograms/min) had a higher 5-yr mean HbA1 (13.3%) than the 26 subjects with AER less than 20 micrograms/min (11.8%; P less than .05). Current HbA1 was correlated with AER (r = +.36, P less than .05) and systolic blood pressure (r = +.49, P less than .01) in females. However, these associations were not observed in males. Positive correlations were found between HbA1 (5-yr mean and current) and serum triglyceride and cholesterol, but only in females was HbA1 inversely related to high-density lipoprotein cholesterol. However, HbA1 was independent of sex, HLA-DR type, and urine C-peptide status. Age adjustment did not change the above results. These analyses suggest that glycemic control is related to AER, systolic blood pressure, presence of microaneurysms, and serum triglyceride and cholesterol concentrations during the first 5 yr of IDDM. However, these associations appear to be predominant in girls.

Adolescent↗

E-business, e-health, e-hospitals.

Many of the major forces of change impacting health care today have technological underpinnings, and many of the less desirable impacts may have technological solutions. Two related technological forces are transacting business, online (e-business) and delivering health care online (e-health).

Diffusion of Innovation↗