Biomedical subjects

N S Fineberg

Publications and source records attributed to N S Fineberg.

At least 37 records · Page 2Linked to original sources

PubMed1997

Flow cytometric DNA analysis of pediatric intracranial ependymomas.

OBJECTIVE: To examine the clinicopathologic features and perform flow cytometric DNA analysis of pediatric intracranial ependymomas to determine whether any of these parameters were predictors of clinical outcome. METHODS: Flow cytometric DNA analysis was performed on 17 paraffin-embedded tumors from patients aged 7 months to 16 years. RESULTS: Seven cases were aneuploid, while the remaining 10 were diploid. Proliferative fractions varied from 1% to 17%. CONCLUSIONS: No correlation between histologic features such as mitotic activity, cellularity, pleomorphism, vascular proliferation, and length of survival was observed. However, the presence of a diploid DNA stemline, elevated proliferative fraction, or young age were associated with a poor clinical outcome and shortened survival times (P < 0.05). Additional studies of larger patient groups with extended follow-up are necessary to confirm these findings.

Adolescent↗

PubMed1996

Gas chromatographic method using photoionization detection for the determination of breath pentane.

Lipid peroxidation is thought to be an important event in the pathogenesis of atherosclerosis. It has been suggested that pentane, which can be formed during the oxidation of omega-6 fatty acids, is a marker of lipid peroxidation. Previous studies have reported elevated breath pentane and serum markers of lipid peroxidation in smokers. However, chromatographic separation of pentane from isoprene in virtually all of these studies was incomplete and the methods used did not resolve pentane into its isomers, n-pentane and isopentane. Additionally, most current methods are complicated, requiring trapping and concentrating steps to obtain adequate sensitivity prior to hydrocarbon analysis. The purpose of the current study was to develop a gas chromatographic system to analyze breath pentane, that addresses the above technical problems and that would provide a simple in vivo method for measuring lipid. n-Pentane and isopentane standards were easily separated from isoprene with a Al2O3/KCI capillary column contained in a portable gas chromatograph equipped with a photoionization detector. The analysis of repeated measures showed a low coefficient of variation for measurements of n-pentane (10%) and isopentane (9%). We measured breath pentane in 27 subjects (15 smokers, 12 non-smokers). There were no significant difference between the baseline and 4 week interval measurements of n-pentane for smokers both before and after cigarette smoking. The within-subject variability data showed that the assay is highly reproducible for both low and high pentane levels in smokers. Smokers were found to have higher levels of both n-pentane and isopentane than non-smokers (P < 0.001). In addition, smokers had further significant elevation of pentane levels 10 min after smoking (P < 0.001), which returned to baseline by 1 h. These studies demonstrate that measurement of breath pentane, using a gas chromatograph with a photoionization detector, is simple and reproducible. Additionally, these results suggest that pentane elevation associated with smoking is secondary to the oxidant effects of cigarette smoke and an important temporal relationship exists between cigarette smoking and breath sample analysis.

Adult↗

PubMed1996

Evaluation using dobutamine stress echocardiography in patients with insulin-dependent diabetes mellitus before kidney and/or pancreas transplantation.

The purpose of this study was to examine the ability of dobutamine stress echocardiography to stratify patients with juvenile onset, insulin-dependent diabetes mellitus who are being considered for kidney and/or pancreas transplantation, into high-or low-risk groups for future cardiac events. Fifty-three such patients underwent dobutamine stress echocardiography before kidney and/or pancreas transplantation. Cardiac events, including cardiac death, nonfatal myocardial infarction, unstable angina, pulmonary edema, and need for coronary revascularization, occurring between the time of the dobutamine stress echocardiogram and the last patient follow-up contact were retrospectively identified. Twenty patients 938%) had an abnormal dobutamine stress echocardiogram. Eleven patients had 15 cardiac events over a mean (+/- SD) follow-up period of 418 +/- 269 days. Event rates were 45% among those with an abnormal, versus 6% among those with a normal dobutamine stress echocardiogram (p = 0.002). The result of the dobutamine stress test independently predicted prognosis in a multivariate analysis (p = 0.003, odds ratio = 12.7). We conclude that dobutamine stress echocardiography accurately stratifies patients with juvenile onset, insulin-dependent diabetes being considered for kidney and/or pancreas transplantation for risk of future cardiac events.

Adult↗

PubMed1996

Cervical dilation from multiple laminaria tents used for abortion.

OBJECTIVE: To quantify the cervical dilation achieved from multiple medium-thick laminaria tents used for 16-26 hours in single applications before abortion. METHODS: In a practice setting, cervical dilation was studied from all abortions done at greater than 8 weeks in which one or more medium-thick laminaria tents were used in a single application for 16-26 hours. Multiple regression analysis was used to quantify results. RESULTS: There was a positive linear regression of dilation against weeks of gestation for all numbers of tents. The more tents, the greater the dilation; the more weeks, the greater the dilation. CONCLUSION: Approximate cervical circumferential dilation from medium-thick laminaria tents under the constraints listed is provided by the formula: Pratt dilation = 12.36 + (2.35 x tents) + (1.79 x weeks).

Abortion, Induced↗

PubMed1996

Glycemic control and transfer of health care among adolescents with insulin dependent diabetes mellitus.

PURPOSE: To describe glycemic control among older adolescents with insulin dependent diabetes mellitus (IDDM) as they move from pediatric to adult-focused health care. METHODS: Prospective cohort study conducted in a university medical center. Participants included 82 consecutive adolescents (50 males and 32 females) with IDDM transferred from a pediatric to an adolescent/young adult diabetes clinic. Main outcome measures were the levels of total stable glycosylated hemoglobin (HbA1) obtained at each visit for up to one year before and after the transfer. RESULTS: The average age of transfer to the young adult clinic was 17.3 +/- 0.8 years. Mean age at onset of IDDM was 9.6 +/- 4.2 years (1.2 to 17.3) with duration of 7.7 +/- 3.9 years (0.7 to 16.1). Glycemic control remained unchanged following transfer (9.9% +/- 1.8 vs 10.2% +/- 1.9; t = 1.6; p = 0.125). Following transfer, both males and females maintained similar levels of glycemic control (9.8% +/- 1.7 and 10.7% +/- 1.8 respectively); although the difference between males and females was significant (t = -2.0; p = 0.048) following transfer, there was no difference in the degree of change by gender (t = -2.0; p = 0.8). In both pediatric and young adult clinics, there was no relationship between duration of IDDM (< 5 vs > or = 5 years) and HbA1. CONCLUSIONS: Transfer to an adult-focused diabetes program appears to have no negative impact on glycemic control.

Adolescent↗

PubMed1996

Immunologic effects of insulin lispro [Lys (B28), Pro (B29) human insulin] in IDDM and NIDDM patients previously treated with insulin.

Insulin lispro [Lys (B28), Pro (B29) human insulin] is a rapidly absorbed analog that has diminished tendency to self-associate. In four open-label, 1-year-long international randomized trials, we contrasted the immunogenicity of insulin lispro versus regular human insulin (RHI) in patients previously treated with insulin who had IDDM or NIDDM. Using a self-blank subtraction assay, we assessed sera for the presence of insulin-specific antibodies (ISA), insulin lispro-specific antibodies (LSA), and cross-reactive antibodies (CRA). Basal insulin needs were provided either with human ultralente (UL) or NPH insulins. After 2 to 4 weeks of therapy with RHI plus UL or RHI plus NPH, 50% of patients were randomly assigned to begin insulin lispro or continue on RHI. At baseline, few pretreated patients had LSA (0-4%) and approximately 10% had ISA, whereas 41-45% of patients with IDDM and 23-27% of patients with NIDDM had CRA (IDDM vs. NIDDM, P < 0.001). Within studies, no significant differences were noted over time in ISA, LSA, or CRA attributable to the type of short-acting insulin. When data were pooled, inconsistent changes were noted in ISA and LSA (LSA were greater in NIDDM vs. IDDM at baseline, P = 0.001, and ISA were greater in IDDM vs. NIDDM at 6 months, P = 0.007). Significant levels of CRA were more common in IDDM at all times (P < 0.001, P = 0.022, and P = 0.002 at baseline, 6 months, and 12 months, respectively). For patients receiving insulin lispro, no significant changes occurred in antibody status among IDDM and NIDDM patients throughout the study (became positive, remained positive, became negative, or remained negative). IDDM patients were more likely to develop or maintain CRA levels (P = 0.008 vs. NIDDM), whereas antibody levels were comparable among positive individuals. No evidence was noted that insulin lispro differs in immunogenicity from RHI in previously treated IDDM and NIDDM patients.

Adult↗

PubMed1996

The role of flow cytometric DNA analysis in determining prognosis of resectable ductal adenocarcinoma of the pancreas.

Carcinoma of the pancreas is a leading cause of cancer mortality in the United States. Improvement in prediction of survival is needed. Flow cytometric analysis as a prognostic tool has produced conflicting results. We retrospectively analyzed the clinicopathologic features, operative factors, and outcome of 39 curative resections for ductal adenocarcinoma of the head of the pancreas performed at Indiana University Medical Center between 1989 and 1994. The group was composed of 20 females and 19 males. Procedures performed were Whipple without vagotomy (n = 5), Whipple with vagotomy (n = 19), pylorus-preserving Whipple (n = 12) and total pancreatectomy (n = 3). Thirty-two tumors were suitable for DNA analysis. Of the 32 patients with flow cytometric data, 33 per cent (3/9) of living patients and 39 per cent (9/23) of deceased patients had aneuploid tumors (P = 0.999). The average S-phase for living patients was 8.3 per cent +/- 3.8 per cent, and 16.1 per cent +/- 13.6 per cent for deceased patients (P = 0.115). In the multivariate analysis, only lymphatic invasion (P = 0.015) and alkaline phosphatase level (P = 0.024) predicted poor survival. Our data show no correlation between flow cytometric DNA ploidy, S-phase analysis, and prognosis in patients undergoing curative resection for ductal adenocarcinoma of the pancreatic head.

Adenocarcinoma↗

PubMed1996

Effects of extracorporeal shock wave lithotripsy to one kidney on bilateral glomerular filtration rate and PAH clearance in minipigs.

PURPOSE: This study examined the acute time course of effects of extracorporeal shock wave lithotripsy (ESWL) on renal hemodynamics in anesthetized minipigs with and without pretreatment with verapamil. MATERIALS AND METHODS: We applied ESWL (2000 shocks, 24 kV, unmodified Dornier HM3), to the right kidneys of isoflurane-anesthetized female pigs. Urine flow and renal hemodynamics were monitored from each kidney via ureteral balloon catheters. Arterial blood pressure and bilateral urine flow, glomerular filtration rate (GFR, insulin clearance) and renal plasma flow (RPF, para-aminohippurate clearance) were monitored for 45 minutes before ESWL, and at 1, 4 and 24 hours after ESWL. RESULTS: Treatment with ESWL consistently caused unilateral hematuria and subcapsular renal hematomas in the shocked kidneys and significantly reduced GFR and RPF in those kidneys at 1 and 4 hours after ESWL. Urine flow was reduced through 24 hours in the shocked kidneys. Renal plasma flow, but not GFR, was significantly reduced in the contralateral (unshocked) kidneys at 1 and 4 hours after ESWL to the other kidneys. Verapamil blunted the ESWL-induced reductions of urine flow, GFR and RPF in the shocked kidneys and eliminated the reduction of RPF in the unshocked kidneys. CONCLUSIONS: These experiments demonstrate that ESWL to 1 kidney acutely impaired hemodynamics in both kidneys and that verapamil attenuated the response in the shocked kidneys and eliminated it in the contralateral unshocked kidneys.

Animals↗

PubMed1994

Dobutamine stress echocardiography: detection of coronary artery disease in patients with dilated cardiomyopathy.

OBJECTIVES: This study attempted to determine the safety and accuracy of dobutamine stress echocardiography for detection of coronary artery disease in patients with dilated cardiomyopathy. BACKGROUND: Detection of regional wall motion abnormalities at rest does not reliably distinguish ischemic from nonischemic cardiomyopathy. Previous studies have shown that dobutamine stress echocardiography safely and accurately identifies coronary artery disease in patients without dilated cardiomyopathy. METHODS: Seventy patients with dilated cardiomyopathy underwent dobutamine stress echocardiography. Echocardiograms were obtained at baseline and at low (5 to 10 micrograms/kg body weight per min) and peak doses of dobutamine. Rest and stress left ventricular wall motion scores were derived from analysis of regional wall motion. Fifty-four subjects underwent coronary angiography. RESULTS: Dobutamine infusion was terminated after achievement of the target heart rate or maximal protocol dose in 49 patients (70%), ischemia in 12 (17%), arrhythmia in 4 (6%) and side effects in 5 (7%). No patient had prolonged ischemia or sustained arrhythmia. Of those with angiographic studies, 40 had significant coronary artery disease (> or = 50% diameter stenosis). Use of the change in global wall motion score index from low to peak dose resulted in a sensitivity of 83% for dobutamine stress echocardiography and a specificity of 71% for detection of coronary artery disease. Sensitivity for detection of triple-, double- and single-vessel disease was 100%, 83% and 69%, respectively. CONCLUSIONS: Dobutamine stress echocardiography safely provides diagnostic information in patients with dilated cardiomyopathy. This technique has high sensitivity for multivessel coronary artery disease but only moderate specificity.

Adult↗

PubMed1994

Salt sensitivity and the blood pressure response to verapamil.

To evaluate the effect of salt responsiveness of blood pressure to the antihypertensive effect of calcium channel blockade, we studied 15 essential hypertensive patients who had previously been characterized with respect to salt sensitivity or resistance of blood pressure. After a placebo period, titration with verapamil in doses of 180 to 480 mg/day was begun until goal blood pressure responses were reached. The study population exhibited a significant (P < or = .007) reduction in systolic and diastolic blood pressure with treatment. There were no significant differences in the response to calcium channel blockade when the subjects were separated into salt-sensitive (n = 8) and salt-resistant (n = 7) subgroups. A significant (P < or = .05) correlation was observed between the age of the subjects and the blood pressure response. In this study verapamil lowered blood pressure in all subjects. We conclude that calcium channel blockade reduces blood pressure in essential hypertensive subjects during a normal sodium intake, independent of salt-sensitivity status.

Adult↗

PubMed1993

The diagnosis of primary aldosteronism and separation of two major subtypes.

BACKGROUND: To develop a simple screening and diagnostic test for primary aldosteronism and to compare it with established techniques. DESIGN: Comparison of several techniques for screening, diagnosis, and differentiation of primary aldosteronism using normotensive and hypertensive subjects. METHODS: Four hundred thirty-four normotensive subjects, 263 essential hypertensive subjects, 48 subjects with primary aldosteronism due to a unilateral adrenal adenoma, and 14 in whom primary aldosteronism was associated with findings of bilateral hyperaldosteronism were studied. Plasma renin activity and plasma aldosterone were measured in venous blood obtained at 8 AM after 2 hours of ambulation and compared with established suppressive (plasma aldosterone) and stimulatory (plasma renin activity) maneuvers used for the diagnosis of primary aldosteronism. RESULTS: The ratio of plasma aldosterone to plasma renin activity provided complete separation of patients with primary aldosteronism from the normal and essential hypertensive groups. Moreover, based on the use of traditional localizing procedures separating unilateral hyperaldosteronism due to a solitary adenoma from bilateral hyperaldosteronism, confirmed by surgical intervention in the former subgroup, the ratio provided differentiation of these two forms of primary aldosteronism. CONCLUSIONS: The use of the plasma aldosterone to plasma renin activity ratio appears to be useful in the screening, diagnosis, and differentiation of unilateral and bilateral forms of primary aldosteronism. These observations may also be applicable to patients receiving some antihypertensive medications.

Adult↗

PubMed1993

In vivo deleterious effects of a right shift of the HbO2 curve during hypoxemia.

We investigated the influence of a right shift of the oxyhemoglobin dissociation curve on tissue oxygenation in two groups of anesthetized rabbits subjected to short periods of graded hypoxia: Group 1 (n = 5) with elevated P50 due to increased RBC 2,3-diphosphoglycerate and adenosine triphosphate and Group 2 (n = 5) with normal P50. Hemoglobin fell progressively in all animals due to blood letting for necessary measurements. During 16% inspired O2 (FIO2), both groups remained stable. During 13% FIO2, arterial pO2 was the same in both groups, but only in Group I did it fall below the crossover point (C.O.P.), which was raised by the high P50. Arterial pH and arterial-venous O2 content difference remained within the normal range in both groups throughout the experiment. During 13% FIO2, animals with high P50 showed a fall in cardiac output and oxygen consumption while animals with normal P50 remained stable. We postulate that when systemic O2 content is sufficiently reduced and tissue O2 extraction is maximal, the O2 needs of the myocardium perfused with a pO2 below the C.O.P. cannot be met: under these conditions cardiac output and systemic O2 consumption fall, presumably due to a reduction in coronary blood flow.

2,3-Diphosphoglycerate↗

PubMed1993

Reference ranges for lymphocyte subsets in pediatric patients.

Peripheral blood lymphocyte subset reference ranges were examined in a large group (N = 130) of healthy pediatric patients ranging in age from 1 month to 17 years. All samples were stained with monoclonal antibodies, processed with a whole blood lysis technique, and analyzed on a flow cytometer. Data analysis demonstrated statistically significant changes in most lymphocyte subsets at age 3 years. The relative and absolute numbers of total lymphocytes, CD2, CD4, and CD19 cells; absolute numbers of CD3 and CD8 cells; and CD4/CD8 ratios were high at birth, decreased during early childhood, and closely approximated adult reference values after age 3 years. The relative numbers of CD8 lymphocytes were low in early childhood and then rose to adult values after 3 years of age. The relative percentage of CD3 cells remained stable over all ages studied. Although "adult" lymphocyte subset reference ranges may be similar to those in children older than 3 years, age-adjusted reference ranges should be used for the early childhood period.

Adolescent↗

PubMed1993

The blood pressure effects of calcium supplementation in humans of known sodium responsiveness.

We examined the interactions between sodium and calcium responsiveness of blood pressure by studying the effects of calcium supplementation in 46 normotensive and hypertensive subjects who had been previously characterized as salt sensitive or salt resistant on the basis of their blood pressure responses to rapid sodium and extracellular volume expansion and contraction. The calcium supplementation study utilized a placebo-controlled, double-blind, randomized crossover design. Subjects received calcium carbonate supplementation (1.5 g/day) for 8 weeks or matching placebo, with 2-week placebo lead-in and crossover periods. For the entire group, no significant blood pressure changes were seen with calcium supplementation. When the subjects were separated on the basis of race or prior salt sensitivity, significant differences were seen. Blacks and salt sensitive subjects exhibited a significant (P < .05) blood pressure decrease when compared to their counterparts. Calcium sensitive subjects had significantly (P < .02) lower levels of plasma renin activity than those not demonstrating a decrease in blood pressure with added calcium. When urinary calcium excretion of subjects previously defined as salt sensitive or salt resistant were compared, the former had significantly (P < .001) higher calcium excretion values at baseline as well as during the placebo and calcium supplementation periods than did the latter. There were no known differences in dietary calcium intake to account for the striking urinary findings. These observations confirm the heterogeneity of blood pressure response to calcium supplementation and demonstrate congruity between sodium and calcium responsiveness of blood pressure in normal and hypertensive humans.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1993

A comparison of two tests for the assessment of blood pressure responses to sodium.

In order to assess the congruity of two different methods for the characterization of blood pressure responsivity to alterations in sodium and extracellular fluid volume balance, we studied 40 normotensive and hypertensive humans. All subjects were initially studied with a protocol of rapid sodium and volume expansion induced by intravenous administration of 0.9% saline (2 L over 4 h) followed by a day of sodium and volume depletion achieved by a low (10 mmol) sodium diet and three 40 mg oral doses of furosemide. Subsequently the subjects underwent a dietary protocol consisting of 5 days of a high (> or = 200 mmol/da) sodium diet followed by 7 days of a low (< or = 15 mmol/day) sodium diet. Blood pressure measurements as well as urinary sodium, potassium, and creatinine excretion measurements were made daily in both studies. A significant (P < .01) correlation was observed between the blood pressure responses to the separate techniques in the same individual. However, not all subjects responded in a similar qualitative fashion to the two maneuvers. The discrepancy was more frequent among subjects having a salt-resistant response to the rapid protocol. The renin response to sodium and volume depletion induced by the low sodium diet and furosemide correlated significantly (P < .001) with the subsequent blood pressure response to the low sodium diet. Subjects defined as salt-sensitive differed from the salt-resistant group by more sluggish renal adaptation to dietary sodium restriction. These findings demonstrate the congruity of two different approaches for the assessment of salt responsivity of blood pressure in humans.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1992

Greater importance of Ca(2+)-calmodulin in maintenance of ang II- and K(+)-mediated aldosterone secretion: lesser role of protein kinase C.

In this study we have investigated various components of the stimulus-secretion coupling process leading to aldosterone secretion from the calf adrenal glomerulosa cells as evoked by angiotensin II (AII) and potassium (K+). The roles of Ca2+, calmodulin and protein kinase C in the sustained phase rather than initiation of aldosterone secretion were of special interest. Our investigations revealed that the reduction of extracellular Ca2+ by EGTA or interruption of Ca2+ influx by nitrendipine at various time points after stimulation with either AII or K+ markedly compromised aldosterone secretion. Calmodulin inhibitors, calmidazolium and W-7 reduced aldosterone secretion profoundly. Agonists of protein kinase C, phorbol ester or diacylglycerol analogues failed to stimulate aldosterone secretion while the protein kinase C inhibitor, H-7, only partially inhibited aldosterone secretion at a concentration which completely inhibited protein kinase C activity. Calmodulin inhibitors produced significantly greater inhibition of aldosterone secretion than inhibitors of protein kinase C.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

PubMed1992

The influence of age on renal function and renin and aldosterone responses to sodium-volume expansion and contraction in normotensive and mildly hypertensive humans.

To determine the effects of age on the responses of renin, aldosterone (PA), sodium excretion, and renal function to provocative maneuvers, we performed volume expansion and contraction in 390 normotensive and 212 hypertensive subjects in the second to seventh decades of life. The subjects were classified as Na-sensitive if their mean blood pressure was 10 mm Hg or more higher after volume expansion than volume contraction. Sodium sensitivity was associated with hypertension and increasing age. Plasma renin activity decreased with age under basal, stimulated, and suppressed conditions; the decrease was greater in hypertensives than in normotensive persons. The PA values were greater in hypertensives than in normal subjects after volume expansion. There was an age-related decrease in PA values after volume contraction in normal, but not in hypertensive, persons. With volume expansion, hypertensive persons exhibited "exaggerated natriuresis." There was an age-related increase in natriuresis in both groups; the increase was greater in hypertensives than normal subjects. Creatinine clearance decreased with age; however, the rate of decrease in this cross-sectional study was not different in hypertensive and normotensive subjects. These observations may have a bearing on why NaCl affects the blood pressures of older individuals more than younger persons.

Adolescent↗

PubMed1992

Flow cytometric DNA analysis of ovarian Brenner tumors and transitional cell carcinomas.

Flow cytometry has been previously used as a method of obtaining prognostic information about ovarian carcinomas using ploidy, DNA index, and S-phase fraction. DNA content has also been assessed in ovarian tumors of low malignant potential. Brenner tumor variants such as metaplastic, proliferating, and low malignant potential, recently designated as intermediate Brenner tumors, and malignant Brenner tumors are unusual tumors that present classification problems. Their histological appearance may not accurately reflect biological activity. We used flow cytometry to analyze paraffin-embedded tissue for DNA content and S-phase in 34 Brenner tumors, three ovarian transitional cell (urothelial) carcinomas (TCCs), and nine normal control ovaries. We correlated histological and clinical features with DNA analysis. Twenty-five Brenner tumors and three ovarian TCCs were acceptable for histogram analysis (coefficient of variation less than 7.0). Thirteen typical, three metaplastic (extensive mucinous or glandular metaplasia), and two proliferating (papillary formation with increased cellularity) Brenner tumors were diploid. One proliferating tumor was tetraploid. The single Brenner tumor of low malignant potential was diploid but had an increased S-phase. Four of five malignant Brenner tumors were aneuploid, and one was diploid. All the TCCs were aneuploid. S-phase was elevated in intermediate and malignant Brenner tumors and TCC. Limited numbers of cases available preclude prognostic prediction based on ploidy in malignant Brenner tumors or primary ovarian TCCs. DNA ploidy and S-phase reflect the intermediate status of metaplastic, proliferating, and low malignant potential Brenner tumors.

Adult↗