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Biomedical subjects

C Binder

Publications and source records attributed to C Binder.

At least 127 records · Page 7Linked to original sources
PubMed1984

Regulation of NK cell activity by prostaglandin E2: the role of T cells.

The influence of T cells on the production of prostaglandins (PGE2) and on PGE2-mediated regulation of natural killer (NK) activity was studied. Supernatants from peripheral blood mononuclear cells (PBMC) and from PBMC depleted of T cells ((PBMC)-T), both of which had been incubated in plastic petri dishes overnight, contained similar amounts of PGE2, as detected by radioimmunoassay and by their potential to inhibit NK activity of peripheral blood mononuclear cells in a 51Cr release assay with K 562 cells as the target population. However, the NK activity of PBMC was inhibited significantly more strongly (P less than 0.005) by PGE2-containing supernatants than was the NK activity of (PBMC)-T. In further assays, in which synthetic PGE2 in concentrations of 10(-4) and 10(-5)M was added, a significant inhibition of NK activity was observed in PBMC populations (P less than 0.05), but not in (PBMC)-T. Thus, T cells did not seem to be involved in the control of PGE2 production, but their presence was necessary for PGE2-mediated inhibition of NK activity.

Adult↗
PubMed1984

Absorption of soluble and isophane semi-synthetic human and porcine insulin in insulin-dependent diabetic subjects.

A double-blind cross-over study of the sc absorption of radiolabelled semi-synthetic human (SHI) and purified porcine (PPI) insulin was made. Absorption of both isophane (n = 10) and soluble insulin (n = 8) was studied. There was no significant difference between the disappearance from the injection site, the plasma free insulin concentrations, or blood glucose levels after sc injection of the isophane preparations. A faster disappearance of the soluble SHI (as judged from T/50 and AUC) was found (both P-values less than 0.01). However, no difference was observed between the plasma insulin concentrations at any time point (P less than 0.05). Blood glucose levels showed no statistical differences between the two soluble preparations. The data indicate minor differences between the pharmacokinetics of SHI and PPI, but these seem of no clinical importance.

Absorption↗
PubMed1984

Spontaneous in vitro immunoglobulin secretion at the diagnosis of insulin-dependent diabetes.

Blood mononuclear cells obtained from 17 newly diagnosed insulin-dependent diabetic (IDDM) patients treated with insulin for 5-7 days were assessed for the number of spontaneous and pokeweed mitogen (PWM)-stimulated immunoglobulin-secreting cells in a reverse haemolytic plaque assay. The spontaneous in vitro immunoglobulin secretion was evanescent and decreased in individual patients within 1-4 months of insulin treatment. Compared to matched controls, 53% (9/17) of the IDDM patients had an elevated spontaneous secretion of immunoglobulin, 41% (7/17) for IgG, 35% (6/17) for IgM, and 35% (6/17) for IgA. The quantities of PWM-stimulated IgG, IgM, or IgA secreting cells in IDDM were comparable to the controls. The IDDM patients with spontaneous immunoglobulin secreting cells had higher fasting C-peptide levels compared to the patients with immunoglobulin-producing cells within the normal range (P less than 0.05). The average titre of islet cell cytoplasmic antibodies was 1:26 in (9 out of 9 were positive) patients with, compared to 1:1 in patients (4 out of 8 were positive) without spontaneous secretion (P = 0.025). These results suggest that the clinical onset of IDDM is associated with a polyclonal B lymphocyte activation and that higher levels of fasting C-peptide islet cell antibodies are associated with this immunoregulatory abnormality.

Adolescent↗
PubMed1984

[Acute heart failure as an initial symptom of juvenile pheochromocytoma. Glucocorticoid therapy as a possible cause of normotension].

A 13 years old girl was admitted with heart failure. Suspected myocarditis could not be proved. Initially slightly elevated blood pressure values normalized but raised again to hypertensive values when glucocorticoid treatment was discontinued; high blood pressure was associated with tachycardia. Determination of catecholamines and metabolites in urine revealed highly elevated levels mainly of norepinephrine. A phaeochromocytoma could be localized sonographically by angiography and selective determinations of catecholamines in samples taken from different parts of the caval vein. An extraadrenal tumor could be removed and the patient's symptoms ceased.

Adolescent↗
PubMed1983

Pharmacokinetics of continuous subcutaneous insulin infusion.

One of the reasons for the variability of blood glucose regulation in Type 1 (insulin-dependent) diabetic patients is the huge variation in subcutaneous absorption of intermediate-acting insulin. We have investigated the variation in insulin absorption during continuous subcutaneous insulin infusion in eight such patients. The content of insulin in the subcutaneous tissue was measured using 125I-labelled insulin. The concentration of free serum insulin and blood glucose was followed from 1 h before and from 7 h after breakfast on two consecutive days. The amount of insulin absorbed during 24 h differed in all cases by less than 3% from the daily insulin dose given by the pumps. Mean insulin absorption rates and mean free insulin concentration showed peak values 30-90 min after meal bolus injections; this was sufficient to maintain near-normal blood glucose. Mean free serum insulin correlated strongly with disappearance of insulin from the subcutaneous tissue (r = 0.98). From the insulin absorption rates and free insulin concentrations during basal constant insulin infusion, the half-time of serum insulin was calculated as 6 min. Compared with the known large variability in the absorption of intermediate-acting insulin, continuous subcutaneous insulin infusion offers a precise and reproducible way of insulin administration resulting in post-prandial serum insulin peaks sufficient to maintain near-normal blood glucose levels. The half-time of serum insulin during subcutaneous infusion corresponds to values for intravenous infusion given in the literature, indicating that local degradation of insulin in subcutaneous tissue is of minor importance.

Adult↗
PubMed1983

Splanchnic and renal metabolism of insulin in human subjects: a dose-response study.

Kinetic analyses of insulin metabolism were performed in 32 healthy subjects with hepatic-venous or renal-venous catheters, in whom steady-state conditions of hyperinsulinemia or hyperglycemia were achieved with the use of the glucose-insulin clamp technique. In the basal state, the splanchnic bed removed 42 +/- 2% of the insulin influx. After graded insulin infusions with maintenance of euglycemia, stable arterial insulin levels of 35-1,430 microU/ml were attained. Splanchnic insulin extraction was constant (approximately 60%) at physiological insulin levels but fell (to 29 +/- 1%, P less than 0.02) at supraphysiological (greater than 500 microU/ml) concentrations. The metabolic clearance rate of infused insulin was essentially constant within the physiological concentration range. Hyperglycemia (+125 mg/100 ml) did not alter splanchnic insulin extraction. Basally, the kidneys extracted 0.04 +/- 0.01 mU X min-1 X kg-1 or 25 +/- 5% of arterial insulin. Renal insulin clearance (3.9 +/- 0.4 ml X min-1 X kg-1) represented over 80% of the extrasplanchnic insulin clearance. Hyperglycemia (+125 mg/100 ml) had no effect on renal insulin extraction. In conclusion, a) both splanchnic and renal insulin removal are independent of glycemia and increase in proportion to plasma insulin concentration within the physiological range; b) splanchnic uptake is the dominant mechanism of removal of insulin from the circulation whether the route of delivery is portal or peripheral; and c) the kidneys account for the greater part of extrasplanchnic insulin metabolism.

Adult↗
PubMed1983

Imitation of normal plasma growth hormone profile by subcutaneous administration of human growth hormone to growth hormone deficient children.

The time course of plasma growth hormone (hGH) levels following sc and im injection of hGH was studied in 12 children with growth hormone deficiency who had received long-term treatment with im injections of highly purified hGH. Also the spontaneous diurnal GH levels in 8 normal children of comparable age were recorded. Blood samples were obtained during 24 h after im and sc injections of 4 IU/m2 hGH and analysed for immunoreactive hGH. While a median peak value of 160 ng/ml (range 135 to 475 ng/ml) was obtained 2 h after im injection, sc injection resulted in a more sustained elevation reaching 41 ng/ml (range 32 to 51 ng/ml) at 6 h subsiding slowly with a median concentration of 15 ng/ml (range 5-24 ng/ml) persisting after 14 h. Gel chromatography demonstrated that the hGH immunoreactivity of blood samples obtained as late as 14 h after sc injection had unaltered molecular size. Seven of the patients were further studied after sc injection of 2 IU/m2 at 20.00 h instead of in the morning. A plasma profile was attained during the night which roughly approximated the average nocturnal plasma pattern of the normal children.

Adolescent↗
PubMed1983

Hepatic extraction of insulin after carbohydrate hyperalimentation.

Peripheral venous plasma insulin and C-peptide concentrations during oral glucose tolerance tests were measured in 7 normal weight non-diabetic subjects before and after 7 days of sucrose hyperalimentation. This induced a deterioration of the glucose tolerance with higher levels of glucose, insulin and C-peptide. The C-peptide to insulin molar ratio as well as the relation between incremental areas under the plasma curves of the two peptides were used as relative measures of the hepatic insulin extraction. Both estimates of hepatic insulin extraction were unchanged by hyperalimentation, suggesting that the induced decreases in glucose tolerance and insulin receptor function are not followed by a decrease in hepatic insulin extraction as found in obese subjects with similar changes in glucose tolerance and insulin receptor function.

Adult↗
PubMed1982

Intensive attention improves glycaemic control in insulin-dependent diabetes without further advantage from home blood glucose monitoring: results of a controlled trial.

Forty-six diabetics treated with twice-daily insulin were seen every two weeks for six months in an intensive education programme aided by regular home urine glucose testing. Control was improved with a decrease in 24-hour urinary glucose excretion (median 138 mmol/24 h (24.8 g/24 h) falling to 70 mmol/24 h (12.6 g/24 h); p less than 0.002), glycosylated haemoglobin concentration (mean 11.4 +/- SD 2.3% falling to 10.4 +/- 1.5%; p less than 0.001), and Diastix score (median 3.0 falling to 1.3; p less than 0.001). There was no reported increase in hypoglycaemia. Thirty-eight of the diabetics proceeded to a nine-month randomised cross-over study of the effect on blood glucose control of monitoring urinary glucose or blood glucose measured visually or by a reflectance meter using appropriate reagent strips. No further improvement in control was observed after home blood glucose monitoring. Nevertheless, 29 out of 37 patients preferred blood to urine glucose monitoring. During both the education and cross-over studies there was evidence of an initial improvement in control followed by deterioration. This was independent of the monitoring method used in the cross-over period and may have been due to waning enthusiasm. Despite patient enthusiasm and other reports to the contrary, home blood glucose monitoring offered no improvement in control over intensive attention and conventional urine glucose monitoring.

Adolescent↗
PubMed1982

Absorption of isophane (NPH) insulin and its clinical implications.

Absorption of 125I-NPH insulin (125I-isophane insulin) (40 IU/ml) was studied in eight diabetics given 50% and 150% of their normal daily dose of insulin. Insulin absorption correlated with plasma insulin (r = 0.97, p less than 0.001) and blood glucose (r = -0.87, p less than 0.01) concentrations. Absorption was slower at higher doses, so that trebling the insulin dose only doubled the amount absorbed over the first 24 hours. The plasma elimination half time (t12) of insulin was about five minutes. Thus, the disappearance of radiolabelled insulin is a reliable and quantitative index of insulin absorption; subcutaneous degradation, if present, is minimal and constant. Changes in dise of intermediate-acting insulin further increases the large variation in insulin absorption. This implies that minor adjustments of intermediate insulin dosage are probably futile.

Absorption↗
PubMed1982

The transient effect of strict glycaemic control on B cell function in newly diagnosed type 1 (insulin-dependent) diabetic patients.

Within 24h of diagnosis, 15 consecutive Type 1 (insulin-dependent) diabetic patients were allocated at random to one of two treatment groups: group A (n = 9, mean age: 28 years, range: 17-35 years) was treated conventionally with one or two daily doses of insulin; group B (n = 6, mean age: 27 years, range: 21-37 years) was treated with nine daily injections of fast-acting insulin for ten days and there-after conventionally as for group A. The mean diurnal blood glucose concentration during the initial ten days of insulin treatment was 11.7 +/- 0.5 mmol/l (mean +/- SEM) in group A and 6.4 +/- 0.3 mmol/l in group B (p less than 0.01). Pancreatic B cell function was evaluated 1, 7, 14, 90, and 180 days after the start of insulin treatment from the C-peptide response to a standard meal. At one and seven days after diagnosis, no difference was found in B cell function between the two groups. After 14 days, the amount of C-peptide secreted during the test meal was 18.0 +/- 2.6 nmol (mean +/- SEM) in group A compared with 29.0 +/- 3.6 nmol in group B (p less than 0.05). After 90 and 180 days, no difference was demonstrated in B cell function. The maximal B cell function observed was similar in the two groups, but occurred earlier in group B (at 14 days) than in group A (at 90 days) (p less than 0.05). This study indicates that strict initial glycaemic control may lead to an earlier improvement in B cell function, but that this improvement is of short duration.

Adolescent↗
PubMed1982

Safety of continuous subcutaneous insulin infusion: metabolic deterioration and glycaemic autoregulation after deliberate cessation of infusion.

To assess the rate of metabolic deterioration and potential risks of failure of continuous subcutaneous insulin infusion during basal insulin delivery, we deliberately stopped infusion in nine insulin dependent diabetics. Plasma glucose, blood 3-hydroxybutyrate and plasma free insulin were measured for 9 h whilst the patients remained supine and fasting. Mean plasma glucose remained unchanged at normal fasting levels for the first hour, then rose to plateau at about 10 mmol/l until the end of the experiment. The final plateau level of glucose varied from patient to patient; two C-peptide secreting diabetics plateaued at low glucose levels. In contrast, blood 3-hydroxybutyrate rose progressively, without plateauing. PLasma free insulin concentrations fell during the withdrawal period and there was a highly significant negative correlation between free insulin and 3-hydroxybutyrate. No patient was more than mildly unwell after 9 h of insulin deprivation. We conclude that under these experimental conditions there is glycaemic autoregulation and that ketones may sometimes be a more appropriate monitor of insulin deficiency or loss of diabetic control than is glucose. Accidental failure of continuous subcutaneous insulin infusion and interruption of basal delivery in resting and fasting diabetics will probably not cause dangerous metabolic or clinical deterioration.

3-Hydroxybutyric Acid↗
PubMed1982

Hormonal and metabolic changes in hepatic cirrhosis.

The hormonal and metabolic response to 50 g oral glucose has been studied in fifteen patients with hepatic cirrhosis and seven control subjects. Fasting blood glucose concentration was similar in both groups but cirrhotics showed higher glucose levels throughout the glucose tolerance test. Fasting serum insulin concentration was raised in the patient group (0.12 +/- 0.02 vs 0.07 +/- 0.01 nmol/l, p less than 0.05 and hyperinsulinaemia persisted after oral glucose. Blood lactate and pyruvate concentrations were elevated in cirrhotic patients, both fasting and post-glucose, while mean blood lactate correlated with mean serum insulin concentrations (rs 0.55, p less than). Plasma glucagon concentrations although highly variable, did not differ significantly in control and cirrhotic subjects before or after oral glucose. Fasting blood glycerol was increased in the patient group (O.11 +/- 0.01 vs 0.06 +/- 0.01 mmol/l, p less than 0.05) but fasting blood ketone body levels were normal and both glycerol and ketone body concentrations fell normally after glucose. Basal serum cortisol levels were similar in patient and control groups but the expected fall in cortisol concentration found in the control group over the test period was absent in cirrhotics. The hormonal and metabolic abnormalities did not correlate with severity of disease assessed by liver function test and abnormalities were not related to the presence or absence of portal-systemic shunting.

Adult↗
PubMed1982

The metabolic effects of moderately severe upper gastrointestinal haemorrhage in man.

The metabolic effects of moderately severe gastrointestinal haemorrhage were investigated in man. Before resuscitation, patients had raised circulating concentrations of glucose, lactate, alanine, glycerol and cortisol. After urgent operation for haemorrhage, metabolite concentrations were similar to those of control patients having elective abdominal surgery, but insulin concentrations were higher and cortisol lower in haemorrhage patients. There were no significant differences in nitrogen excretion between haemorrhage patients and their controls, but urinary 3-methyl-histidine excretion by haemorrhage patients was lower indicating decreased muscle protein breakdown. Decreased amino acid release from muscle might account for previously reported imparied wound healing after haemorrhage.

Alanine↗
PubMed1981

Effect of strict blood glucose control on residual B-cell function in insulin-dependent diabetics.

In 14 insulin dependent diabetics past their initial remission period B-cell function was evaluated using a test meal before and after 1 week of strict blood glucose control, and again 3 weeks later when the patients were outpatients on conventional therapy. Eight patients with fasting C-peptide above 0.07 nmol/l improved their B-cell function significantly (p Less Than 0.05) during the period of strict blood glucose control. However, the improvement was of short duration and was absent 3 weeks later in most patients. Six patients with fasting C-peptide below or equal to 0.07 nmol/l had no significant improvement in B-cell function during the period of strict control. The study shows that B-cell function and degree of blood glucose control are related in patients with fasting C-peptide above 0.07 nmol/l, and that B-cell function can change within days.

Adolescent↗