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Biomedical subjects

H von Schenck

Publications and source records attributed to H von Schenck.

At least 19 recordsLinked to original sources

Fat metabolism and its response to infusion of insulin and glucose in patients with advanced chronic obstructive pulmonary disease.

In order to investigate fat metabolism and the regulation of lipolysis and blood fuel metabolites by insulin, nine patients with chronic obstructive pulmonary disease (COPD) with chronic hypoxaemia and seven healthy control subjects of similar age were investigated by determination of the turnover rate of free fatty acids (TOR), using 1-14C-oleic acid as a tracer, and arterial concentrations of FFA, glycerol and 3-hydroxybutyrate. The measurements were performed in the basal state and during insulin and glucose infusion, aiming at euglycaemia at insulin levels of 50 and 100 mU l-1. The subjects' ages were 64 +/- 2.7 and 66 +/- 1.1 (mean +/- SEM) years in the COPD and control groups, respectively. TOR was 0.73 +/- 0.06 and 0.52 +/- 0.02 mmol min-1 (P < 0.05) in the basal state, 0.33 +/- 0.04 and 0.30 +/- 0.02 at an insulin level of 50 mU l-1 and 0.32 +/- 0.08 and 0.24 +/- 0.02 at an insulin level of 100 mU l-1, in the COPD and control groups, respectively. Arterial FFA concentration was 0.98 +/- 0.08 and 0.75 +/- 0.06 mmol l-1 (P < 0.05) in the basal state in the COPD and control groups, respectively. During the clamp, the decrease in FFA mirrored that in TOR. The results show that the state of lipolysis is increased in severe COPD patients with chronic hypoxaemia. Furthermore, the results suggest a reduced effect of insulin in lipolysis.

Aged

Regulation of insulin-like growth factor binding protein-1 (IGFBP-1) in insulin-dependent diabetes mellitus. Effects of hyperglycaemia and insulin.

The aim of the present study was to characterize the effect of 44 h of hyperglycaemia on diurnal levels of insulin-like growth factor binding protein-1 (IGFBP-1), insulin-like growth factor-1 (IGF-1), growth hormone (GH) and glucagon in 7 well-controlled subjects with insulin-dependent diabetes mellitus (IDDM). Hyperglycaemia (approximately 15 mmol/l) was induced by a glucose infusion, while the degree of insulinisation was similar to that of a corresponding period with near normoglycaemia (approximately 6.9 mmol/l). Hyperglycaemia for 44 h did not alter the normal diurnal IGFBP-1 levels when the degree of insulinisation was unchanged. The diurnal secretion pattern of IGFBP-1 was preserved in both genders and without any difference between the control and hyperglycaemic periods. However, the IGFBP-1 levels were increased in these IDDM subjects despite a peripheral hyperinsulinemia. An inverse correlation was found between IGFBP-1 and peripheral insulin levels both during periods of rapid changes in IGFBP-1 and insulin concentrations (i.e. morning hours) as well as during the total 24-h sampling period. Total IGF-1 levels were low, but no further decrease was seen after 24 h of hyperglycaemia in the presence of unchanged insulin levels. In conclusion, the present study clearly shows that the increased IGFBP-1 level seen during poor metabolic control in IDDM is not caused by hyperglycaemia. Glucose levels per se do not influence either total IGF-1 or IGFBP-1 concentrations in well-insulinised diabetic patients.

Adult

Comparison of seven formulae and isoelectrofocusing for determination of intrathecally produced IgG in neurological diseases.

Seven different formulae and agarose isoelectrofocusing (AIF) using immunolabelling for IgG were compared for their ability to discriminate between intrathecally produced IgG and transudated IgG in cerebrospinal fluid. All reference limits were set to a specificity of 97.5% (reference group, n = 211). The probability of a positive test (p+) was evaluated for 112 patients with multiple sclerosis (MS), 42 with meningitis, 114 with noninflammatory diseases affecting the central nervous system (CNS), 23 with Guillain-Barré syndrome, and 56 with various diseases not affecting the CNS. Agarose isoelectrofocusing had the best diagnostic sensitivity (93%) for MS, combined with a low p+ (0-19%) for other diseases. Among the formulae, the IgG extended index and Reiber's hyperbolic formula were equivalent, giving high (75-79%) diagnostic sensitivity for MS combined with low p+ (4-22%) for other diseases. All other formulae, although sensitive for MS, had a higher rate of false positive results.

Algorithms

Insulin-antagonistic effects of pulsatile and continuous glucagon infusions in man--a comparison with the effect of adrenaline.

The insulin-antagonistic effects of pulsatile (3 min pulses every 20 min) and continuous glucagon infusions were studied over 4 h with the euglycemic clamp technique in healthy subjects. Comparisons were made to the effect of a continuous adrenaline infusion. Glucose production and utilization were evaluated with D-3-3H-glucose and somatostatin was used in all studies to inhibit the endogenous release of insulin and glucagon. The amount of glucagon given during the pulsatile infusions (27% of that during continuous infusion) was adjusted so that the peak glucagon levels were the same as during the continuous infusion (372 +/- 22 and 365 +/- 20 ng/L, respectively). The insulin-antagonistic effects of pulsatile and continuous glucagon infusions were similar during the first hour and imparied the insulin effect with 44 +/- 8 and 47 +/- 6%, respectively. However, when infused continuously, the effect of glucagon declined rapidly, whereas the effect of a pulsatile infusion decreased more slowly and was evident for 3 h. Raising the glucagon level 4-fold restored the insulin-antagonistic effect again suggesting that the cells had become desensitized. In contrast, the insulin-antagonistic effect of adrenaline was persistent throughout the 4 h of the study and impaired insulin action with 54 +/- 2%. The effects of pulsatile and continuous glucagon infusions were entirely due to the stimulation of glucose production while that of adrenaline mainly was due to inhibition of peripheral glucose uptake. In conclusion, the acute stimulatory effect of glucagon on glucose production is transient but it is better maintained when given as intermittent pulses rather than as a continuous infusion. In contrast, the insulin-antagonistic effect of adrenaline on glucose uptake is persistent for at least 4 h.

Adult

Lipoprotein metabolism following gastroplasty in obese women.

In order to elucidate the long-term alterations in cholesterol transport and esterification as a part of the changes in the carbohydrate and lipoprotein metabolism subsequent to calorific restriction, 15 obese women were investigated before and after treatment with vertical banded gastroplasty. Insulin resistance and production, lipid levels in plasma, lipoproteins and the lecithin: cholesterol acyl transferase (LCAT) rate were assessed. There was a 60% decrease in mean calorific intake six months after surgery. A slight hyperglycaemia was almost normalized concomitant with a reduction of serum insulin and C-peptide after 1 year. The very low density lipoprotein (VLDL) level was unchanged. The high density lipoprotein (HDL) levels tended to rise after 1 year, when there was a significant increase of the HDL-2 subfraction. The lipid levels in the lipoprotein fractions showed a rise in mean HDL-2 cholesterol. Both the molar and fractional rates of LCAT were decreased. These results suggest that long-term calorific restriction reduces insulin resistance and production, and lowers VLDL levels and VLDL and cholesterol synthesis. However, the low density lipoprotein cholesterol levels are unchanged, probably because of a decrease in the previously elevated fractional cholesterol removal.

Adult

The acute effect of insulin on tissue plasminogen activator and plasminogen activator inhibitor in man.

The present study was performed to elucidate the acute effect of insulin on levels of tissue plasminogen activator (t-PA) and plasminogen activator inhibitor of endothelial cell type (PAI-1). Nine middle-aged, non-obese and non-smoking men were studied during a hyperinsulinemic, euglycemic glucose clamp for 2 h. Plasma insulin level during the clamp averaged 84 +/- 12 mU/l and euglycemia was maintained at 4.9 +/- 0.6 mmol/l. The t-PA activity gradually increased (75% mean increase after 2 h, p less than 0.001) and the PAI-1 activity decreased (49% mean decrease after 2 h, p less than 0.001) during the clamp. t-PA activity decreased and PAI-1 activity increased after the insulin infusion was ceased, but they were still 48% higher and 38% lower, respectively, after 60 min. PAI-1 and t-PA activities were not affected by saline infusion for 2 h. Thus, acute changes in the insulin levels lead to rapid alterations in the fibrinolytic system even when euglycemia is maintained. These effects may be induced by insulin itself or by the concomitant activation of the sympatho-adrenal system during the euglycemic clamp.

Blood Glucose

Characterization of the insulin-antagonistic effect of growth hormone in man.

The insulin-antagonistic effect of growth hormone was characterized by infusing the hormone at three different infusion rates (6, 12 or 24 mU.kg-1.min-1) for one h in 11 healthy subjects. The insulin effect was measured with the euglycaemic clamp technique combined with D-(3-3H)-glucose infusion to evaluate glucose production and utilization. A control study with NaCl (154 mmol.l-1) infusion was also performed. The insulin levels during the clamps were similar in all studies (36 +/- 0.2 mU.l-1). Peak growth hormone levels were reached at 60 min (growth hormone 6 mU.kg-1.h-1: 31 +/- 5; growth hormone 12 mU.kg-1.h-1: 52 +/- 4 and growth hormone 24 mU.kg-1.h-1; 102 +/- 8 mU.l-1). The insulin-antagonistic effect of growth hormone started after approximately 2 h, was maximal after 4-5 h (approximately 39% inhibition of glucose infusion rate between control and growth hormone 24 mU.kg-1.h-1) and lasted for 6-7 h after peak levels. The resistance was due to a less pronounced insulin effect both to inhibit glucose production and to stimulate glucose utilization. Growth hormone infusion of 12 mU.kg-1.h-1 induced a similar insulin-antagonistic effect as the higher infusion rate whereas 6 mU.kg-1.h-1 induced a smaller response with a duration of 1 h between 3-4 h after peak levels of growth hormone. The present study demonstrates that growth hormone levels similar to those frequently seen in Type 1 (insulin-dependent) diabetic patients during poor metabolic control or hypoglycaemia, have pronounced insulin-antagonistic effects.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Pancreatic ductal morphology and function in primary Sjögren's syndrome.

In six patients with primary Sjögren's syndrome defined with HLA-antigens and no clinical signs of pancreatitis, the pancreatic ductal morphology (as described by endoscopic retrograde pancreatography), serum pancreatic enzymes, and fecal fat excretion were examined and secretin test was carried out. Further, oral glucose tolerance test with concomitant determination of serum insulin and C-peptide were done. All patients had at least two pathological signs of exocrine function and/or ductal morphology. There was no evidence of endocrine malfunction. The findings are suggestive of the existence of a clinically silent pancreatitis, perhaps of autoimmune etiology.

Aged

Demonstration of a phospholipase A2 inhibitor in human plasma and in plasma from the European hedgehog (Erinaceus europaeus).

1. Endogenous phospholipase A2 (PLA2) inhibitors in human plasma and in plasma from the hedgehog (Erinaceus europaeus) were demonstrated. 2. The PLA2 activity increased 45-fold in human plasma when a PLA2 binding factor was removed. Furthermore, two peaks of PLA2 inhibitory activity were found after DEAE-chromatography. 3. High levels of PLA2 inhibitory activity was found in plasma from the European hedgehog, E. europaeus. 4. The molecular weight was estimated to 140,000. 5. On DEAE-chromatography two peaks were found which were chromatographically similar to the PLA2 inhibitors in human plasma.

Adult

Long-term efficacy and safety of simvastatin alone and in combination therapy in treatment of hypercholesterolaemia.

The 3-years efficacy and safety of the 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor simvastatin (S) (previously called synvinolin or MK-733) has been studied in single and combined therapy with cholestyramine (C) in 48 hypercholesterolaemic patients. Plasma lipids, lipoproteins and apolipoproteins A-I and B, and blood safety tests (haematology, liver function, creatine phosphokinase (CPK), creatinine, blood glucose and thyroid function) were determined regularly throughout the study. Extensive ophthalmological examinations with particular focus on the lens were done before initiation of therapy and at every 6 months during drug treatment. Maximal reductions of mean plasma total cholesterol concentration (34% with S; 47% with S + C) and low-density lipoprotein (LDL)-cholesterol concentration (42% with S; 56% with S + C) were achieved after 4 weeks on full-dose therapy. During continued treatment, years 1 through 3, the reduction of mean plasma total cholesterol was 26-29% with S alone, and 31-41% with S + C. Significant reductions of plasma triglycerides (15-27%) and very low density lipoprotein (VLDL) triglycerides (10-27%) were achieved in the group treated with S as single therapy. In this group there was also a significant increase (10-14%) of high-density lipoprotein (HDL)-cholesterol. In liver aspartate (AST) and alanine (ALT) aminotransferases, as well as alkaline phosphatase (ALP), minor and variable, but usually transient, increases were seen. Repeated ophthalmological examinations did not demonstrate any drug-related side effects. It is concluded that simvastatin is a safe and efficient cholesterol-lowering drug for long-term therapy, both as a single drug and in combination with cholestyramine.

Adult

Pancreatic exocrine and endocrine function in patients with pancreas divisum and abdominal pain.

Pancreatic exocrine and endocrine function is described in 29 patients with pancreas divisum and upper abdominal pain. The diagnosis was made by endoscopic pancreatography (ERP) after cannulation of the major, as well as the accessory, papilla in all patients. At ERP, six patients had signs of marked and six patients moderate pancreatitis, whereas 17 patients were free from pancreatitis changes. Pancreatitis was found in the dorsal anlage in 12 patients (41%) of whom seven (24%) had similar alterations also in the ventral anlage. Fecal fat excretion was increased in 48% of the patients, and abnormal serum levels of pancreatic enzymes were found in more than one-third. Impaired insulin release was detected in 21% of the 28 patients examined following ingestion of oral glucose. Including an additional patient with manifest diabetes, 24% (7/29) had signs of endocrine insufficiency. The serum-insulin, serum-C-peptide and insulin/glucose pattern following an oral glucose load reflected the degree of severity of pancreatitis changes at ERP. Altogether, 66% of the patients had morphological and/or functional evidence of pancreatic affection.

Abdominal Pain

Effect of fish oil treatment on plasma lipoproteins in type III hyperlipoproteinaemia.

Nine patients with type III hyperlipoproteinaemia and homozygosity for the apolipoprotein E2 isoform were treated with 15 g daily of MaxEPA, a fish oil preparation rich in eicosapentaenoic acid (2.7 g daily) and docosahexaenoic acid (1.8 g daily) for 16 weeks. Plasma lipoprotein and apolipoprotein concentrations were compared with those obtained during treatment with an olive oil preparation. MaxEPA treatment decreased plasma median total cholesterol, triglyceride and apolipoprotein B concentrations by 16, 53 and 19%, respectively. Plasma median very low density lipoprotein (VLDL)-cholesterol, triglyceride and apolipoprotein B concentrations were reduced by 45, 62 and 75% respectively, while the abnormal VLDL-cholesterol/triglyceride ratio remained unchanged. Individual reductions of VLDL concentrations varied considerably, for VLDL-cholesterol between 10 and 75%. In the majority of cases the abnormal late pre beta-bands on agarose electrophoresis, typical for type III hyperlipoproteinaemia normalized to pre beta-mobility on MaxEPA treatment. LDL-cholesterol and apolipoprotein B tended to increase after 8 weeks on MaxEPA but decreased again after 16 weeks. Median plasma high density lipoprotein cholesterol and apolipoprotein A-I did not change during MaxEPA treatment. It is concluded that MaxEPA have decreasing effects on plasma VLDL lipid and apolipoprotein concentrations in apolipoprotein E2 homozygous type III hyperlipoproteinaemia but that this effect is variable and unpredictable.

Adult

Characterization of the late posthypoglycemic insulin resistance in insulin-dependent diabetes mellitus.

The insulin effect (6.5 to 7.5 hours) following hypoglycemia was studied with the euglycemic clamp technique in eight patients with insulin-dependent diabeteses mellitus (IDDM). The results were compared with a control study with the same insulin infusion, but where hypoglycemia was prevented by a glucose infusion. Glucose production (Ra) and utilization (Rd) were evaluated with D-(3-3H) glucose infusion. Hypoglycemia (glucose nadir, 1.5 +/- 0.1 mmol/L) caused a marked increase in cortisol and growth hormone, whereas the release of adrenaline and, in particular, glucagon was low. The plasma free insulin levels were similar in the studies, including during the clamp periods. The glucose infusion rates (GIR) were significantly lower after the hypoglycemia as compared with the control study (control, 2.4 +/- 0.3; hypoglycemia, 1.5 +/- 0.3 mg/kg x min; P less than .05). Thus, hypoglycemia induces prolonged insulin resistance. The posthypoglycemic insulin resistance during a moderate hyperinsulinemic (approximately 30 mU/L) clamp was mainly due to a decreased insulin effect on glucose utilization (control, 2.9 +/- 0.2; hypoglycemia, 2.2 +/- 0.2 mg/kg x min; P less than .02), whereas the insulin effect on glucose production was not significantly different after hypoglycemia.

Adult

Fish scales as biosensors for catecholamines.

Certain fish scales contain specialized cells (chromatophores) with pigment granulas, which can be dispersed or aggregated in the cells. The degree of aggregation is determined by a transmitter substance, noradrenaline, released by the sympathetic nerve endings in the skin. Isolated scales from, for example, cuckoo wrasse (Labrus ossifagus) retain a large sensitivity to externally applied noradrenaline (or more generally catecholamines) for several weeks. The degree of aggregation in isolated scales can be measured objectively by simple photometric techniques. We demonstrate in this paper how fish scales can be used to monitor catecholamine levels in human blood plasma. A discussion of other potential biosensor applications of this intact biological receptor-effector system is also given.

Animals

Postprandial hyperglycaemia following a morning hypoglycaemia in type 1 diabetes mellitus.

The occurrence of hyperglycaemia following a morning hypoglycaemic episode was studied in nine patients with Type 1 diabetes. Each patient was studied twice, once following induced hypoglycaemia and once in a control study when hypoglycaemia was prevented by glucose infusion. After the initial hypoglycaemic/control period the patients were maintained on their regular insulin regimens and were given standard meals. Hypoglycaemia induced postprandial hyperglycaemia (3.1 +/- 0.8 mmol l-1 above control) which lasted for about 8 h. Maximal growth hormone levels were seen 40 min after glucose nadir (control 7.8 +/- 3.2, hypoglycaemia 74.0 +/- 12.3 mU l-1) and the magnitude of the hyperglycaemia was related to the growth hormone levels following the hypoglycaemia (r = 0.80, p less than 0.01).

Adult

Prevalence of protein-energy malnutrition in a large population of elderly people at home.

The prevalence of protein-energy malnutrition (PEM) was examined in 1206 randomly selected elderly people aged 65 to 80 years living in their own homes. Nutritional assessment was based on weight loss, weight index, triceps skin fold, arm muscle circumference, serum albumin and prealbumin, and delayed cutaneous hypersensitivity (DCH) reaction. The prevalence of PEM was 5 per cent. If people with signs of inflammation were excluded, the prevalence of PEM was 3.5 per cent. When other nutritional indices, used by other authors among hospitalized patients, were applied to our sample prevalence values from 2.6 to 4.1 per cent were obtained. the prevalence was not related to sex or age. DCH increased the sensitivity of the screening method but causes of anergy other than PEM must be taken into account. It is concluded that PEM, in a degree shown to impair the prognosis at hospital, does occur among elderly people at home in an industrialized country.

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