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Biomedical subjects

J S Soeldner

Publications and source records attributed to J S Soeldner.

At least 73 records · Page 4Linked to original sources

Retinal vascular reactivity to norepinephrine and angiotensin II in normals and diabetics.

Retinal arterial vasoconstriction induced by an infusion of angiotensin II or norepinephrine was investigated in eight normal controls (N), nine diabetics without retinopathy (DNR), and 10 diabetics with retinopathy (DR) by color fundus photographs taken before and after the infusions. Image analysis was done by a semiautomated computerized microdensitometer using a videoscanner. Normal controls and diabetics without retinopathy had a significant reduction in diameter compared with diabetics with retinopathy, who failed to constrict arterioles in response to either vasopressor. The mechanism of this phenomenon is unclear. Semiautomated computerized microdensitometry is reproducible and appears to be a sensitive technique to evaluate the vascular reactivity of the retinal vasculature.

Adult↗

Clinical consequences of acquired transfusional iron overload in adults.

We assessed the clinical sequelae of transfusional iron overload in 15 nonthalassemic adults (40 to 71 years of age) with anemias requiring transfusions. Iron loading had been present for less than four years in 14 patients. The number of units of blood transfused ranged from 60 to 210 (mean, 120). Liver-biopsy specimens in 10 patients contained seven to 26 times the normal amount of iron and typically showed focal portal fibrosis. Left ventricular cardiac function was impaired in only the most heavily transfused patients or in those with coexisting coronary-artery disease, All patients had glucose intolerance associated with significantly reduced insulin output, compared with controls (P < 0.01). Pituitary reserve of ACTH was limited in 10 of 12 patients, and that of gonadotropin in five of 13. We conclude that widespread subclinical organ dysfunction can result from transfusional iron overload developing in adulthood. The pattern of organ involvement resembles that encountered in idiopathic hemochromatosis.

Adult↗

Treatment of diabetes mellitus by devices.

A very important aspect of diabetes mellitus is whether or not normalization or near-normalization of blood glucose and/or other metabolites and hormones may reduce or eliminate the chronic complications of this disease. To answer this question and to provide a more "physiologic" approach to insulin administration, a constellation of devices have reached the stage of clinical investigation. These include small portable pump systems that can provide variable rates of insulin infusion via the subcutaneous intravenous or intraperitoneal routes. In addition, bedside artificial "beta cells" having the capability of providing insulin infusions, with the rate varying as a function of continuous glucose measurements, are available for short-term studies. Under development are implantable continuous infusion devices and implantable glucose sensors that could in the future lead to a miniaturized implantable glucose-controlled insulin administration system.

Animals↗

Reproducibility of the densitometric analysis of fluorescein angiograms.

Computer-aided operator-interactive densitometry was applied to assess the reproducibility or retinal-fluorescein angiograms. To achieve this, the fundus camera images of glass tubings of various diameter filled with fluorescein of varying concentrations were subjected to densitometric analysis. These studies were carried out repeatedly at 9-micrometer and 29-micrometer scanning resolutions by three observers and thus the inter- and intra-operator errors could be estimated. The scanned data were analyzed as both optical densities and intensities for some of the measurements. In both analyzing modes good linearity was obtained when the densitometric response was plotted against tubing diameter for various concentrations. To determine the reproducibility of transit time and retinal circulation time analyses, a randomly selected patient's angiogram was repeatedly analyzed by three observers and compared. From these data the inter- and intra-operator errors were also determined for successive frames and the reproducibility of the area under the dye dilution curves for both arteries and veins was computed. The overall densitometric reproducibility was found to be good; however, practical usefulness of the retinal circulation time remains to be established.

Angiography↗

The determination of glycosylated hemoglobins in rats using high pressure liquid chromatography.

Glycosylated hemoglobins (GHb) or fast hemoglobins (FH) are minor components of hemoglobin that so far have been quantified in men, monkeys, and mice, and they are elevated in diabetic subjects of all these species. Since the rat is a useful model for experimental diabetic studies, hemolysates from streptozotocin-induced diabetic rats were analyzed for FH fractions using a high pressure liquid chromatography method. In a long-term study (3 mo), the maximal increment of the FH fractions was achieved after 5 wk of diabetes (from 5.67% +/- 0.41% SD to 10.80% +/- 0.74%) supporting the notion that the biosynthesis of these compounds occurs continuously during the lifespan of the red cell. In a short-term study, however, an elevation of the FH by 11% after 2 days and by 26% after 6 days of diabetes was noticed suggesting that a rapid increase of the FH may occur in relation to rapid changes of the glucose level.

Animals↗

Insulin resistance and monoclonal gammopathy.

Two maturity-onset diabetic patients developed severe insulin resistance during the course of monoclonal gammopathies. One patient had Waldenström macroglobulinemia and the other had multiple myeloma with IgA gammopathy. The maximum insulin binding capacity (MIBC) was 121 U/liter and 54.7 U/liter, respectively, during insulin resistance. The clinical courses of insulin resistance paralleled the activity of the monoclonal gammopathies (MG) with the insulin resistance disappearing after the monoclonal gammopathies were controlled. Six other diabetic patients with concurrent insulin resistance and monoclonal gammopathies are reviewed.

Aged↗

Stability of hemoglobin AIc levels on repetitive determination in diabetic out-patients.

Hemoglobin (Hb) AIc levels were measured biweekly for 14 weeks in 49 diabetic out-patients and 20 nondiabetic subjects. As conventional indices of diabetes control, urine tests were performed four times per day, and plasma glucose concentrations were measured 2 h post breakfast. The diabetic group ranged in age from 15-73 yr and in duration of diabetes from 6 months to 45 yr. Eleven subjects were on diet therapy alone, three were on oral hypoglycemic agents, and 35 were on insulin therapy. The nondiabetic group ranged in age from 18-65 yr. On entry to the study, the mean (+/-SD) Hb AIc and plasma glucose levels of the diabetic group (8.60 +/- 2.11% and 142.5 +/- 99.9 mg/dl) were significantly higher than in the control group (4.68 +/- 0.60% and 102.4 +/- 21.7 mg/dl; P less than 0.001) and remained so throughout the study. The mean coefficient of variation for Hb AIc did not differ significantly between the control group and either the diet therapy or insulin therapy diabetic groups. Urine test values averaged over 2-week periods for each diabetic subject showed a high degree of stability. The mean Hb AIc levels for individual diabetic subjects correlated with the mean plasma glucose levels (r = 0.544; P less than 0.001), proportion of 2% urine tests (r = -0.798; P less than 0.001). These data provide further support for Hb AIc as a measure of diabetes control and, in addition, provide the first direct evidence that a single Hb AIc determination in a 3-month period is adequate for this purpose when the subjects are on a stable therapeutic regimen.

Adolescent↗

Insulin half-life in man after trauma.

To explore the possibility that the half-life of insulin changes after trauma, five control subjects and 19 severe trauma patients received intravenous glucose (0.5 gm/kg) in 5 minutes to raise rapidly the insulin levels, followed immediately by 300 mg of intravenous diazoxide over 5 minutes to inhibit any further insulin secretion. Serial blood samples were analyzed for immunoreactive insulin, and insulin half-life was calculated. The baseline insulin level was 13.4 +/- 3.8 microU/ml in the trauma group 10.4 +/- 3.1 microU/ml in the control group. During the glucose infusion, insulin levels rose to 177.0 +/- 56.0 microU/ml in the controls and to 127.0 +/- 27.0 microU/ml in the trauma group. The rise in the control subjects was greater (P less than 0.03) than the rise in the trauma patients. After diazoxide, insulin levels fell to 25.0 +/- 6.2 microU/ml and 25.0 +/- 6.6 microU/ml, respectively. Insulin half-life in the control subjects was 5.2 +/- 0.3 min and 3.9 +/- 0.2 min in the trauma group (P less than 0.019).

Adult↗

Measurement of hemoglobin A1 by liquid chromatography and by agar gel electrophoresis compared.

We compare measurement of total fast hemoglobin (HbA1) by "high-performance" liquid chromatography and by electrophoresis on agar gel. Blood samples were obtained from a diverse population (n = 222): offspring of two diabetic parents, diabetic patients with and without retinopathy, diabetic and non-diabetic pregnant women, patients in the coronary-care unit, and normal persons. Precision studies with a normal and an above-normal A1 sample resulted in overall CVs of 9.0% and 4.6% for the electrophoretic method and 4.4% and 2% for the chromatographic method. Linear regression analysis of values for total fast hemoglobin for the complete sample population and for each subgroup showed results of the electrophoretic method to be in excellent agreement with those by the chromatographic method. We conclude that the agar gel electrophoretic method offers a reproducible means for HbA1 determination that is comparable to the HPLC method in terms of accuracy and is highly suited for routine laboratory use.

Adolescent↗

Pancreatic alpha and beta cell function in familial dysbetalipoproteinemia.

Resistance to both insulin and glucagon have been considered as possible causes of primary hypertriglyceridemia. In the present research, we have compared insulin and glucagon secretion in five hyperlipidemic patients with familial dysbetalipoproteinemia with five normolipidemic control subjects matched for age, sex and adiposioty. Plasma insulin and glucagon concentrations mesaured during standard oral glucose tolerance and arginine infusion tests were similar in the two groups. Blood glucose fell transiently in the controls, but not in the patients, during the Himsworth test (100 g glucose orally plus 0.05 U insulin per kg body weight intravenously). There were no significant differences in plasma FFA concentrations and responses during all tests between the groups. The percentage reduction in plasma triglyceride concentration during infusion of arginine was similar in the two groups. These results suggest that the patients with familial dysbetalipoproteinemia were slightly less insulin sensitive than the controls. However, primary insensitivity to glucagon or insulin does not appear to be fundamental to the pathogenesis of hyperlipidemia in familial dysbetalipoproteinemia.

Adult↗

Pancreatic alpha cell response to alanine during and after normal and diabetic pregnancies.

Pancreatic alpha cell response to oral alanine was assessed in the third trimester of pregnancy and in the puerperium in 16 insulin-dependent diabetic and 7 normal pegnant women. Insulin response was also measured in the nondiabetic subjects. The nondiabetic subjects had higher basal glucagon and insulin levels as well as a greater response to oral alanine stimulation at 34 weeks' gestation than at 6 weeks post partum. In addition, basal levels of both hormones remained low at a time remote from pregnancy (9 months post partum), indicating both hyperinsulinemia and hyperglucagonemia in the postabsorptive state in normal human pregnancy. The secretory response of glucagon and insulin or oral alanine was blunted at 6 weeks post partum in the nondiabetic subjects. This suggests that the late puerperium may not be an appropriate "nonpregnant control period" for metabolic studies. During pregnancy, basal and stimulated glucagon levels were not significantly different in diabetic and normal women. Despite higher concentrations of blood glucose in diabetic women, basal and stimulated glucagon secretion was equivalent in the 2 groups. No pegnancy-induced increment in glucagon secretion was evident in insulin-treated diabetic subjects. Thus hyperglucagonemia does not contribute to the increased requirements for insulin during pregnancy in these women.

Administration, Oral↗

Insulin secretory dynamics after two consecutive intravenous stimulations with glucose and/or tolbutamide.

Intravenous glucose and/or tolbutamide administered in two consecutive pulses 30 and 60 min apart to the same subjects using identical doses showed that insulin secretory responses was altered during a subsequent stimulation and that this was modulated by the time factor. Insulin response was more sustained after the second glucose pulses and the insulin peak response was delayed and diminished if the second glucose dose was given 30 min after the first, but not if given 60 min later. It is suggested that the beta-cell membrane might remain partially depolarized above a certain glucose level or that a postulated signal relay mechanism might become saturated. Responses to two tolbutamide pulses did not show these characteristics; however, the second insulin response was smaller than the first. When the first pulse was glucose and the second tolbutamide, or vice versa, the second responses were altogether different from those elicited by the double doses of either tolbutamide or glucose. To explain these characteristic patterns of insulin secretory dynamics, the existence of occult glucose receptors on the beta-cell that are opened up by tolbutamide was postulated. These studies do not support the two-pool theory, or at least restrict it to glucose-stimulated insulin response. The positive correlations between the first and the second insulin responses in all tests argue strongly against the existence of an insulin feedback mechanism in man.

Adult↗