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Biomedical subjects

R E Gleason

Publications and source records attributed to R E Gleason.

At least 19 recordsLinked to original sources

Autonomic function in type I diabetes mellitus complicated by nephropathy. A cross-sectional analysis in the presymptomatic phase.

The purpose of this study was to determine the prevalence of parasympathetic and sympathetic autonomic dysfunction in long-standing type I diabetics with established nephropathy and to correlate autonomic function with cardiac risk factors. We used prospective analysis of heart rate variations to standardized testing and 24-hour blood pressure control prior to enrollment in a study utilizing various methods of intense diabetic control to prevent deterioration of kidney function. The settings were outpatient clinical research units. The patients were 42 type I diabetics with proteinuria (total urinary protein > or = 300 mg/day or urinary albumin > or = 100 mg/day) and creatinine clearance > or = 30 mL/min. Heart rate variation during respiratory cycles with change in posture from supine to upright, and during the Valsalva maneuver was recorded by a computerized method. Mean arterial blood pressure was recorded for 24 h by a computerized method. Heart rate variations in this group were abnormal during timed respiratory cycles in 26 of 40 patients (56%), during changes in posture in 15 of 40 patients (38%), and during Valsalva maneuver in 13 of 34 patients (38%) whose retinal disease permitted Valsalva testing. Blunted day/night mean arterial pressure ratios occurred in 18 of 41 (44%) patients and were more severe in men than in women (1.00 v 1.06, P < or = .05). Absence of deep tendon reflexes was associated with an increased incidence of both parasympathetic (respiratory rate variation) and sympathetic (postural rate variation) abnormalities (both P < or = .05). Loss of vibration sensation was not associated with autonomic functional abnormalities.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

The 24-h kinetics of leucine oxidation in healthy adults receiving a generous leucine intake via three discrete meals.

The significance of meal size and frequency for the 24-h leucine tracer-balance technique was examined. Continuous measurements of leucine oxidation throughout a 24-h d were performed in six healthy, young adults who were given a weight-maintaining diet (188 kJ.kg-1.d-1; 1 g protein.kg-1.d-1) for 6 d followed by primed, continuous intravenous infusions of L-[1-13C]leucine and [15N-15N]urea. The 24-h study was started at 1800 on day 6 and three equal discrete meals were given at 2000, 0600, and 1200. Leucine oxidation was assessed from plasma [13C]alpha-ketoisocaproate enrichment and 13CO2 excretion. The mean (+/- SD) leucine oxidation after each meal (over 6 h) was not significantly different (P > 0.5) among the three discrete meals: 20.0 +/- 3.9, 20.2 +/- 1.9, and 20.3 +/- 2.4 mg.kg-1.d-1 for the meals given at 2000, 0600, and 1200, respectively. Twenty-four-hour leucine oxidation was 75.0 +/- 7.8 mg.kg-1.d-1 for a leucine dietary intake of 80 mg.kg-1.d-1 (and approximately 9.7 mg tracer.kg-1.d-1). The 24-h pattern in leucine oxidation was paralleled by plasma leucine concentrations. Further, leucine oxidation and urea excretion predicted relatively similar values for 24-h protein oxidation. These data are compared with results from our similar previous studies using a multiple-small-meal feeding protocol.

Adult

Effect of acute ethanol ingestion on prolactin in menopausal women using estradiol replacement.

Epidemiologic studies suggest that women who consume ethanol are at an increased risk for developing breast cancer. Two randomized, crossover studies were performed to examine the effects of ethanol on prolactin in menopausal women using transdermal estradiol. In study 1, transdermal estradiol patches (0.15 mg) were administered to menopausal women (n = 7) the day before ethanol administration. At 8.00 h, the women ingested ethanol (1 ml/kg, 95% ethanol) or an isocaloric carbohydrate drink. Prolactin levels were measured frequently for 6.3 h. Serum ethanol levels reached a broad peak from 40 to 100 min after initiation of ethanol ingestion. Serum prolactin levels were significantly higher after ethanol ingestion than after the isocaloric carbohydrate drink ingestion (p < 0.03). Study 2 was identical to study 1 except that the transdermal estradiol patches were removed after completion of ethanol or carbohydrate ingestion. In study 2, serum prolactin was greater after ethanol ingestion than after carbohydrate ingestion (p < 0.001). In menopausal women using transdermal estradiol, acute ethanol ingestion is associated with an increase in serum prolactin.

Administration, Cutaneous

Chest X-ray screening improves outcome in lung cancer. A reappraisal of randomized trials on lung cancer screening.

It is believed that population-based screening for cancer should be advocated only when screening reduces disease-specific mortality. Four randomized controlled studies on lung cancer screening have been conducted in male cigarette smokers, and none has demonstrated reduced mortality. Accordingly, no organization that formulates screening policy advocates any specific early detection strategies for lung cancer. Yet, despite this public policy against screening, there is considerable evidence that chest x-ray screening is associated with earlier detection and improved survival. Two randomized trials, the Memorial Sloan-Kettering and Johns Hopkins Lung Projects, were specifically designed to evaluate the effectiveness of sputum cytologic study. Both evaluated the efficacy of the addition of sputum cytologic studies to annual chest radiographs, and both demonstrated that cytologic study did not favorably influence outcome. All individuals in experimental and control groups in both studies had annual chest radiographs. Because survival rates observed in both studies were about three times higher than predicted, based either on the National Cancer Institute's Surveillance Epidemiology and End Results database or based on the American Cancer Society's annual Cancer Statistics, raises the possibility that the periodic chest radiographs performed in all patients in both studies contributed to an improved outcome. In the Mayo Lung Project and in the Czechoslovak study on lung cancer screening, the experimental groups underwent a program of relatively intensive and regular rescreening with chest radiographs and sputum cytologic study, while the control groups underwent either less-frequent rescreening or no rescreening. In both studies, the screened groups achieved meaningful improvements in stage distribution, resectability, and survival. However, increases in cumulative incidence of lung cancer in the experimental group in both studies (which in the Mayo Lung Project reached statistical significance) prevented significant improvements in survival from translating into corresponding reductions in mortality. The possibility that screening may be associated with lung cancer "overdiagnosis" has been widely postulated to account for higher survival and incidence rates and equivalent mortality rates. However, analysis of autopsy information and of disease outcome in individuals with screen-detected early stage lung cancer who do not undergo surgical resection strongly supports the conclusion that screening does not lead to overdiagnosis of lung cancer. Similarly, lead-time and length bias do not adequately account for the differences in cumulative incidence observed in the Mayo and Czech studies.(ABSTRACT TRUNCATED AT 400 WORDS)

Bias

The effects of ethanol on the clearance of estradiol in postmenopausal women.

OBJECTIVE: To determine whether acute alcohol ingestion affects the pattern of decline of circulating E2 levels after removal of transdermal E2 patches. DESIGN: A randomized, placebo-controlled, crossover study. SETTING: The study was performed in the Clinical Research Center of the Brigham and Women's Hospital. PARTICIPANTS: Twelve healthy postmenopausal women were enrolled. INTERVENTIONS: Transdermal E2 patches, 0.15 mg, were applied 13 hours before subjects ingested alcohol (1 mL/kg 95% ethanol) or carbohydrate placebo punch. The patches were removed immediately after drink ingestion. MAIN OUTCOME MEASURES: Estradiol, estrone (E1), and ethanol levels were measured. RESULTS: Serum samples were obtained for 40 minutes before drink ingestion and 5 hours after drink ingestion and E2 patch removal. At the time of patch removal, E2 levels rose acutely over 10 minutes and then decreased rapidly, suggesting a bolus effect that was more marked after ethanol ingestion. After ethanol ingestion and patch removal the half-life of E2 was calculated to be 378 minutes, and after carbohydrate punch and patch removal 245 minutes. There were no significant changes in E1 concentrations over the time course of the study between groups. CONCLUSIONS: Ethanol ingestion may decrease E2 clearance after removal of transdermal E2 patches.

Administration, Cutaneous

Acute and delayed effects of corticotropin-releasing hormone on dopamine activity in man.

Interactions between the hypothalamic-pituitary-adrenal (HPA) axis and central dopamine systems have been hypothesized to play a role in the pathophysiology of psychosis, but the normal physiology of HPA axis-dopamine interactions has not been fully defined. We report results from two uncontrolled pilot studies which explored the effects of ovine corticotropin-releasing hormone (CRH) on dopamine activity in healthy human subjects. Administration of CRH did not produce changes in plasma levels of homovanillic acid (HVA), the major dopamine metabolite, over the subsequent 3.5 hours. However, when the effects of CRH were followed over a longer period in a small subgroup, we found that CRH administration produced a two-fold rise in plasma HVA levels 20 hours later, without affecting plasma levels of 3-methoxy-4-hydroxyphenylglycol (MHPG), a major metabolite of norepinephrine. Thus, the findings of these pilot studies suggest that CRH may exert delayed but not acute effects on dopamine activity in man.

Adrenocorticotropic Hormone

Effect of pharmacological daytime doses of melatonin on human mood and performance.

Melatonin (10, 20, 40, or 80 mg, PO) or placebo was administered at 1145 hours on five separate occasions to 20 healthy male volunteers and the effects on serum melatonin levels, mood, performance, and oral temperature were monitored. Subjects were studied between 0930 and 1700 hours. A battery of interactive computer tasks designed to assess performance and mood was completed, oral temperature was measured, and blood samples were taken for serum melatonin radioimmunoassay. The areas under the time-melatonin concentration curve (AUC) varied significantly in proportion to the various melatonin doses. Compared with placebo treatment, all melatonin doses significantly decreased oral temperature, number of correct responses in auditory vigilance, response latency in reaction time, and self-reported vigor. Melatonin also increased self-reported fatigue, confusion, and sleepiness.

Adult

Screening for lung cancer re-examined. A reinterpretation of the Mayo Lung Project randomized trial on lung cancer screening.

In the 1970s, three randomized trials, each involving approximately 10,000 male subjects, were carried out to determine the value of lung cancer screening in cigarette smokers. These studies have been widely interpreted as providing strong evidence that screening does not contribute to decreased death rates, and, accordingly, the American Cancer Society firmly recommends against lung cancer screening. No randomized trial, however, has evaluated screening for lung cancer in women, who currently comprise 39% of the lung cancer population. The trials performed at Memorial-Sloan Kettering and at Johns Hopkins were designed so that subjects were randomized to either a single screen (annual chest x-ray alone) or a dual screen (annual chest x-ray and every-4-month sputum cytology) group. While the results of both revealed no difference in mortality between the groups, these studies were designed to examine the value of sputum cytology, and no conclusion regarding the efficacy of chest x-rays can be inferred. In the Mayo Lung Project, patients were randomized to a screened group in which a chest x-ray and sputum cytology were obtained every 4 months or to a control group in which an annual chest x-ray and cytology were simply recommended. The results indicate that after 6 years, more lung cancers were detected among the 4,618 men in the screened group (206 cases, 4.46%) than in the 4,593 men in the control group (160 cases, 3.48%). The screened group showed a superiority over the control subjects in resectability rate (46% vs 32%) and 5-year survival (33% vs 15%). However, the number of cancer deaths was slightly greater in the screened (122) than in the control group (115), and, consequently, the mortality rates were not significantly different among the groups. An "overdiagnosis bias" has been suggested to account for the increased number of lung cancers detected in the screened vs the control population in the Mayo Lung Project. This explanation is statistically plausible, but, given the status of lung cancer as the most lethal of malignancies, is biologically unlikely. An alternative hypothesis is that chance alone might have accounted for the observed 0.98% difference in lung cancer detection rates. Were this the case, then 46 additional cases would have been detected in the control group had this chance event not occurred.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult

Usefulness of left ventricular size and function in predicting survival in chronic dialysis patients with diabetes mellitus.

To identify patients at high risk for sudden death, a group of stable patients on maintenance dialysis with diabetes mellitus were studied for up to 135 months to determine if there were clinical, laboratory or echocardiographic predictors of high risk. Eighty-two patients on maintenance dialysis who underwent clinical, laboratory evaluation and echocardiography were enrolled and followed for a mean of 25 months for cardiac and noncardiac complications. Thirty-seven patients with normal wall motion and left ventricular (LV) internal diameter had a mean survival of 35.8 months; 28 patients survived greater than 12 months. Seven patients with normal LV wall motion and dilated LV cavities had a mean survival of 45.7 months; 7 patients survived greater than 12 months. Fifteen patients with abnormal LV wall motion and normal internal LV dimensions had a mean survival of 17 months; 7 patients survived greater than 12 months. Twenty-three patients with both abnormal LV wall motion and dilated LV cavities had a mean survival of 7.8 months; 5 patients survived greater than 12 months. Although echocardiographic abnormalities predicted cardiac mortality at 6 and 12 months, the combination of an abnormal standard electrocardiogram at baseline, clinical history of angina pectoris, and prior documented myocardial infarction or congestive heart failure did not. When the study group was divided by mode or duration of dialysis, presence or absence of diabetes, or use of cardioactive drugs, echocardiographic LV wall motion abnormalities remained the most important determinant of survival.

Adult

Preoperative evaluation for diabetic renal transplantation: impact of clinical, laboratory, and echocardiographic parameters on patient and allograft survival.

OBJECTIVE: To assess the impact on renal transplant patients and graft survival of clinical, laboratory, and echocardiographic parameters commonly measured prior to surgery. PATIENTS: Forty-seven consecutive diabetics with preoperative echocardiograms at the time of transplantation. METHODS: Clinical history, standard chest roentgenogram, electrocardiogram, blood tests, echocardiograms, and HLA testing at baseline; follow-up from 2 to 7 years with periodic reassessment of graft function. RESULTS: Patient survival did not appear to be influenced by age, sex, or type of allograft. A history of either myocardial infarction, congestive heart failure, or angina was present in 15 patients with 3-year survival of 50% (72% if not present, p less than 0.05). Histocompatibility testing did not impact on survival. Serum sodium, potassium, calcium, phosphate, and calcium-phosphate product did not discern different survival groups. A hematocrit greater than 30% was present in 15 patients with 3-year survival of 43% (73% if not present, p less than 0.05). Greater than 10% antibody sensitization of the recipient resulted in a 3-year survival of 38% in eight patients (68% if not present, p less than 0.05). Radiologic evidence of cardiomegaly or congestive heart failure and standard electrocardiographic evidence for left ventricular hypertrophy or strain did not impact on survival. Echocardiographic measurements of left ventricular end-diastolic diameter, posterior wall thickness, or ejection fraction were also not predictive. Increased end-systolic diameter (10 patients, 30% 3-year survival versus 69%, p less than 0.05) and decreased velocity of circumferential fiber shortening (11 patients, 45% 3-year survival versus 71%, p less than 0.05) both appeared to be related to survival. Increased accuracy of prediction could be obtained by adding risk factors so that a history of coronary artery disease and increased end-systolic diameter predicted 3-year survival of 42% versus 82% if neither was present. In terms of graft survival, no clinical, radiographic, or electrocardiographic result yielded predictive information. Among the laboratory tests, only highly antibody-sensitized patients (eight patients, 0% 3-year survival versus 66% 3-year survival, p less than 0.001) showed different survival patterns. Echocardiographic elevated end-systolic diameter predicted a significantly (p less than 0.001) decreased graft survival (3-year survival 33% versus 63%). CONCLUSION: Preoperative prediction of patient and graft survival in diabetic renal transplantation may be enhanced by echocardiographic assessment of systolic load and function. For patients with normal systolic function, whose hematocrit is below 30%, with preformed antibodies less than 10%, renal transplantation has an excellent prognosis; invasive cardiac procedures are not likely required. Since these risk factors are likely additive, a high-risk group may be identified. These latter patients should undergo coronary angiography.

Adult

Comparison of frame size and body mass index methods of assessment in the study of blood lipids.

This study compared frame size and body mass index methods of assessment in relation to blood lipid levels. The data were obtained from the records of 84 men and 193 women who voluntarily participated in health fairs held at two suburban hospitals. Significant relationships and differences were found between the anthropometric and lipid variables studied. The two methods of classification denoted moderate association and reflected some divergence in classification between them.

Adult

Menstrual cyclicity of CA-125 in patients with endometriosis.

OBJECTIVE: To examine the serum levels of CA-125 in the menstrual, follicular, and luteal phases of the menstrual cycle in women with endometriosis and to determine if serum CA-125 levels drawn during menses improve the clinical utility of the test in diagnosing endometriosis. DESIGN: Serum CA-125 was measured in the menstrual, follicular, and luteal phases of the cycle preceding surgery. CA-125 levels for each phase were categorized by postoperative diagnosis and endometriosis stage. SETTING: The reproductive endocrine unit of a tertiary care university-affiliated hospital. PATIENTS: A total of 65 patients were recruited from the Fertility and Endocrine Unit and the Gynecology Service of Brigham and Women's Hospital. MAIN OUTCOME MEASURE: Serum CA-125 levels were measured by an immunoradiometric assay and were stratified by menstrual cycle phase, diagnosis, and stage of endometriosis. The menstrual cycle phase was confirmed by serum estradiol and progesterone measurements. RESULTS: Serum CA-125 levels in patients with stages II to IV endometriosis were significantly elevated in the menstrual phase compared with levels drawn in the nonmenstrual follicular and luteal phases. The sensitivity and specificity of CA-125 for the diagnosis of endometriosis were not significantly better in the menstrual than in the follicular or luteal phases. CONCLUSIONS: Despite menstrual cyclicity of CA-125, measurement of serum CA-125 during menses does not improve the clinical utility of the test in the diagnosis of endometriosis.

Antigens, Tumor-Associated, Carbohydrate

The effect of consecutive day inseminations on semen characteristics in an intrauterine insemination program.

This study demonstrates a statistically significant decrease in semen volume, sperm concentration, and sperm motility in samples obtained on the 2nd day of consecutive day inseminations in an IUI program. This diminution in semen characteristics persists despite sperm washing. The effects of a second ejaculation on semen parameters in oligospermic and asthenospermic men were mixed. Thus, in general, sperm-washing procedures cannot overcome the natural reduction in semen quality produced by frequent ejaculations. Clinicians may wish to use this information in timing IUI cycle inseminations.

Ejaculation

Plasma amino acid concentrations in healthy elderly men and women.

Postabsorptive plasma concentrations of the large neutral amino acids (LNAAs) were measured in 74 elderly (age 71 +/- 8 y) and 138 young (age 26 +/- 5 y) healthy subjects. Plasma concentrations of valine, leucine, and isoleucine were significantly lower in young females than in young males. This gender-related difference was not observed among elderly subjects because aging was associated with a significant rise in plasma LNAAs in females but not in males. Multiple-regression analysis of plasma amino acid concentrations from female subjects revealed a significant and positive effect of age on plasma valine, leucine, isoleucine, phenylalanine, and tyrosine but not on plasma tryptophan or methionine. Tryptophan was the only amino acid to exhibit a significant response to age in males, consisting of a 14% decline in the elderly subjects. Percentile ranges are presented for young and elderly females and males for each of the amino acids.

Adult

Melatonin concentrations in the sudden infant death syndrome.

To examine a possible relationship between pineal function and the sudden infant death syndrome (SIDS), samples of whole blood, ventricular cerebrospinal fluid (CSF) and/or vitreous humor (VH) were obtained at autopsy from 68 infants (45 male, 23 female) whose deaths were attributed to either SIDS (n = 32, 0.5-5.0 months of age; mean +/- S.E.M., 2.6 +/- 0.2 months) or other causes (non-SIDS, n = 36, 0.3-8.0 months of age 4.3 +/- 0.3 months). The melatonin concentrations were measured by radioimmunoassay. A significant correlation was observed for melatonin levels in different body fluids from the same individual. After adjusting for age differences, CSF melatonin levels were significantly lower among the SIDS infants (91 +/- 29 pmol/l; n = 32) than among those dying of other causes (180 +/- 27; n = 35, P less than 0.05). A similar, but non-significant trend was also noted in blood (97 +/- 23, n = 30 vs. 144 +/- 22 pmol/l, n = 33) and vitreous humor (68 +/- 21, n = 10 vs. 81 +/- 17 pmol/l, n = 15). These differences do not appear to be explainable in terms of the interval between death and autopsy, gender, premortem infection or therapeutic measures instituted prior to death. Diminished melatonin production may be characteristic of SIDS and could represent an impairment in the maturation of physiologic circadian organization.

Age Factors

A randomized double-blind prospective trial of two doses of gestrinone in the treatment of endometriosis.

The purpose of this randomized double blind prospective trial was to study the efficacy and safety of two doses of oral gestrinone in the treatment of endometriosis. Six patients received gestrinone 1.25 mg twice weekly (group I) and six patients received gestrinone 2.5 mg twice weekly (group II). Patients underwent pretreatment and post-treatment laparoscopies and their endometriosis scores were recorded. The mean total endometriosis scores declined significantly from 20.0 +/- 5.2 (mean +/- standard error of the mean) pretreatment to 9.5 +/- 3.9 post-treatment in group I and from 19.1 +/- 4.8 pretreatment to 7.1 +/- 2.1 post-treatment in group II. A total of 67% of patients reported side effects. This study suggests that oral gestrinone 1.25 mg or 2.5 mg twice weekly is efficacious and safe in the treatment of endometriosis.

Adult

Cardiac conduction defects associated with aortic and mitral valve calcification in dialysis patients.

The prevalence of aortic valve and mitral valve or mitral annular calcification by echocardiography was studied in 66 dialysis patients and correlated with results of 24-h ambulatory and resting ECG data and 12-month survival. The well-known association of mitral valve or mitral annular calcification with cardiac conduction defects was confirmed. Those patients with mitral valve or mitral annular calcification demonstrated a higher prevalence of first-degree atrioventricular block and bundle branch block. Despite advanced age and these conduction defects, those patients with mitral valvular calcification did not show decreased survival at 12 months.

Aortic Valve