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Biomedical subjects

H Laube

Publications and source records attributed to H Laube.

At least 19 recordsLinked to original sources

A reliable test to detect impending pump failure during long-term support on the Novacor N100 Left Ventricular Assist System.

The Durastudy is a new surveillance protocol to detect impending pump failure in Novacor N100 Left Ventricular Assist Systems implanted for the long term. Our patient, a 54-year-old man with a history of dilated cardiomyopathy and contraindications for heart transplantation, received a Novacor pump in May 1995 and did not experience sustainable ventricular recovery during the subsequent 3 years. After more than 3 years of support, symptoms of pump wear were detected in this patient, through application of the Durastudy protocol. This enabled us to electively exchange the pump at 3.8 years. Our patient remained in New York Heart Association functional class I until he died in July 1999 of causes unrelated to the pump, after some 1,514 days of support. This, we believe, still constitutes a world record.

Heart-Assist Devices↗

Recovery from end-stage ischemic cardiomyopathy during long-term LVAD support.

A patient with ischemic cardiomyopathy and extremely reduced left ventricular function (left ventricular ejection fraction=0.10) presented to our institution for cardiac transplantation. Because of his worsening condition he was placed on the Novacor left ventricular assist device. During 3 months of support his left ventricular function recovered and he successfully underwent percutaneous transluminal coronary angioplasty and minimally invasive direct coronary artery bypass grafting procedures; subsequently he could be weaned from the left ventricular assist device and discharged. The patient is no longer considered for cardiac transplantation.

Angioplasty, Balloon, Coronary↗

The effect of acarbose on insulin sensitivity and proinsulin in overweight subjects with impaired glucose tolerance.

Insulin sensitivity is impaired in overweight subjects with IGT and is accompanied by hyperinsulinemia, a condition, that might promote early B-cell exhaustion. Twelve subjects were recruited for a double-blind trial using either 100 mg of acarbose or placebo for three months. Insulin sensitivity was measured by hyperglycemic clamp and with the minimal model. Baseline characteristics such as body weight, BMI, blood glucose, HB-A1c and serum lipids did not change throughout the study period. The steady state glucose infusion rate (SSGIR) improved significantly following acarbose. The insulin sensitivity as measured by clamp (MI) or minimal model, (SI), however, increased only descriptively (p = 0.08). The fasting proinsulin was raised in all subjects during pretreatment. Following acarbose, the proinsulin dropped from 20.3 +/- 12.9 to 13.6 +/- 7.1 ng/ml, but remained unchanged in the placebo group. Due to the high variability of values and the low number of subjects in this study, differences were only descriptive and did not reach significance (p = 0.08). The proinsulin/insulin ratio, however, significantly decreased after 3 months of acarbose treatment. Acarbose might therefore be considered recommendable for the protection of the B-cell function and for delaying the transition of IGT to overt NIDDM.

Acarbose↗

A diet enriched in protein accelerates diabetes manifestation in NOD mice.

Diet modifies the development of insulin-dependent diabetes mellitus in animals and in humans. We examined female non-obese-diabetic (NOD) mice, a diabetes-prone mouse strain with 70% spontaneous diabetes incidence and metabolic abnormalities in non-overtly diabetic litters. They were fed a diet containing 55% (n = 27) or 15% (n = 26) protein, respectively, after weaning. At an age of 30 weeks, non-diabetic NOD mice were submitted to an intravenous glucose tolerance test (0.5 g/kg body weight; blood samples were taken after 2, 4, 8, 10, 15, 20 and 30 min) and to perfusion of the pancreas (stimulation media were Krebs-Ringer-Hepes buffer with 5 mmol/l glucose, 30 mmol/l glucose and 5 mmol/l glucose plus 19 mmol/l arginine). Diabetic mice were removed from the experiment. Serum glucose concentration and body weight were monitored weekly. Food ingestion was checked at an age of 11 weeks. On average, the onset of diabetes was diagnosed in mice on a high-protein diet (19.7 +/- 1.3 weeks) 4 weeks earlier than in mice on a low-protein diet (23.5 +/- 1.1 weeks; P < 0.05). Non-diabetic NOD mice on a high-protein diet showed significantly better glucose tolerance (as determined by the glucose disappearance rate) and mean insulin secretion (at 30 mmol/l glucose). No difference in the serum glucose concentration between non-diabetic mice on the low-protein diet or high-protein diet could be proved. In non-diabetic mice on the high-protein diet the body weight and food ingestion exceeded those of mice on the low-protein diet (P < 0.05). High insulin secretion and glucose tolerance in non-diabetic mice may reflect the capacity of beta-cells to adapt; however, beta-cells tend to be destroyed under such circumstances. Thus, a high-protein diet promoted the onset of diabetes, but it did not increase significantly the incidence of the disease.

Aging↗

Intensive therapy in adult insulin-dependent diabetes mellitus is associated with improved insulin sensitivity and reserve: a randomized, controlled, prospective study over 5 years in newly diagnosed patients.

Optimal blood glucose levels and normal insulin sensitivity are aims in the treatment of insulin-dependent diabetes mellitus (IDDM). Insulin sensitivity and insulin reserve are closely interrelated. It is essential to know more about both of these parameters at clinical diagnosis, because their preservation may delay the occurrence of diabetes-related complications. B-cell function is likely to be retained for a longer period in patients with adult onset of the disease compared with children. In this study, intensive insulin treatment was initiated in newly diagnosed adult patients to determine if it preserved endogenous insulin secretion longer than conventional therapy. Forty-nine patients with newly diagnosed diabetes were carefully categorized as having IDDM according to clinical and serological criteria. They were randomized to an intensive (I group) or conventional (C group) insulin therapy and evaluated for 5 years. Every 6 months, a check-up included glucagon-stimulated C-peptide (GSCP), hyperglycemic glucose clamp with arginine bolus, euglycemic-hyperinsulinemic clamp, and screening for microalbuminuria, retinopathy, and neuropathy. At the end of the study, hemoglobin A1c (HbA1c) was 6.3% +/- 1.9% in the I patients and 8.1% +/- 2.1% in the C patients (P < .001). Blood glucose concentrations less than 3.5 mmol/L were more frequent in the I group than in the C group (P < .05). Insulin sensitivity (M/I) and GSCP were higher in intensively treated patients after 5 years (M/I, I group 40 +/- 10 nmol x kg(-1) x min(-1) x pmol/L1 v C group 21 +/- 11, P < .005; GSCP, I group 0.6 +/- 0.2 nmol/L v C group 0.19 +/- 0.11, P < .005). The prevalence of peripheral neuropathy was significantly lower in the I group at the end of the study. In conclusion, intensive therapy is more effective in the preservation of insulin action and reserve. In our patients, no case of severe hypoglycemia was observed, indicating that intensive therapy was safe in these patients.

Adult↗

Effect of dietary protein intake on insulin secretion and glucose metabolism in insulin-dependent diabetes mellitus.

Adult-onset insulin dependent diabetes mellitus (IDDM) is associated with significant residual insulin secretion. The process leading to the ultimate destruction of B cells may be influenced, among other factors, by the quality and amount of ingested protein. Using a standardized food questionnaire, we matched 13 individuals with normal protein (NP; 0.74 +/- 0.08 g/kg.day) and high protein (HP; 1.87 +/- 0.26 g/kg.day) intake from a sample of 117 newly diagnosed IDDM patients according to sex, age, body mass index, and energy intake. Nondiabetic control subjects were also selected. Dietary habits did not change significantly over an observation period of 1 yr. Glucagon-stimulated C peptide was significantly higher in the NP compared to the HP group (0.71 +/- 0.06 vs. 0.50 +/- 0.04 nmol/L; P < 0.002). NP food was associated with higher overall insulin sensitivity in both patients and nondiabetic subjects. Hepatic glucose output was significantly increased in individuals with HP intake [HP IDDM, 14.8 +/- 0.6 vs. NP IDDM, 12.7 +/- 0.7 (P < 0.01); HP control, 12.2 +/- 0.5 vs. NP control, 10.9 +/- 0.5 (P < 0.01 mumol/kg.min). Insulin-mediated suppression of hepatic glucose production was impaired in diabetic patients with high protein intake, but not in patients with normal protein diet. Gluconeogenesis estimated from 13C enrichment in breath and plasma was increased in individuals on a HP diet. We conclude that a NP diet is accompanied by delayed progression of the continuous loss of endogenous insulin in IDDM. This phenomenon is possibly due to decreased insulin demand on the B cells and/or reduced hepatic glucose production favoring enhanced insulin sensitivity.

Adult↗

[Endoventricular patch-plasty for reconstruction of ventricular geometry and pump function in myocardial aneurysm].

This report deals with the first experience with endoventricular patch plasty in patients suffering from left ventricular aneurysm. The early postoperative results in 18 patients operated upon during January and May 1995 are encouraging. All patients survived the procedure. In contrast to patients operated on according to a linear resection technique the postoperative outcome and the early results are much better with this technique. We recommend the endoventricular patch plasty on a beating heart.

Aged↗

Natural course of insulin sensitivity and insulin reserve in early insulin-dependent diabetes mellitus.

Preservation of endogenous insulin in insulin-dependent diabetes mellitus (IDDM) may prevent the occurrence of diabetes-related complications. Therefore, it is important to known about insulin reserve and insulin sensitivity at clinical manifestation. Twenty-four patients (aged 23 +/- 6 years) were evaluated for 2 years starting at the day of clinical manifestation. Insulin secretion was stimulated by glucagon, arginine, and glucose on separate days. Insulin sensitivity was evaluated by hyperinsulinemic-euglycemic clamp. Two control groups were established, one consisting of age-, weight-, and sex-matched healthy individuals, the other of patients with diabetes of long duration (6 to 13 years). Sensitivity improved from 30% of normal at baseline to 84% after only 2 weeks in the newly manifested patients. Subsequently, insulin released by nonglucose stimuli increased by 75%. Glucose-induced first-phase insulin secretion did not recover. After 2 years, sensitivity was 20% less than normal and glucagon-stimulated C-peptide (GSCP) was 0.64 +/- 0.20 nmol/L (0.41 +/- 0.19 at baseline, P < .002). Insulin sensitivities in euglycemic and hyperglycemic conditions were closely correlated. In conclusion, improvement of insulin sensitivity precedes and is possibly a prerequisite for the recovery of residual insulin in early IDDM.

Adult↗

Clinical spectrum of the MELAS mutation in a large pedigree.

INTRODUCTION: MELAS is most often due to an mentally transmitted A-G transition mutation of mitochondrial DNA (mtDNA) at position 3243. In this study we report on the clinical spectrum associated with the mutation in the largest family reported so far. PATIENTS AND METHODS: In a family with three MELAS cases we identified 47 persons at risk for the mutation; sufficient data was available on 29. Mitochondrial disease was diagnosed in two of 9 deceased numbers (posthumous molecular analysis in one); 27 surviving family members underwent examination and 25 a molecular analysis of mt DNA from lymphoblasts. Then had a muscle biopsy and two were later autopsied. RESULTS: All 26 cases investigated by molecular analysis showed the mutation at position 3243. The 18 symptomatic patients without stroke-like episodes had sensorineural hearing loss in 15 cases, diabetes in 6, nephropathy in 7, mild myopathy in 4, cardiomyopathy in 2, cerebellar disease in 4 and mental retardation in 2 cases. Eight carriers were asymptomatic. Autopsy showed > 80% mutant mt DNA in all tissues except blood (20%) examined in a MELAS patients, but < 20 mutant mt DNA in all tissues except lever (40%) and kidney (70%) in a patient with hepatopathy, renal failure and diabetes. Histologic and biochemical studies of muscle biopsy were often non-informative. CONCLUSIONS: The mutation of mt DNA at position 3243 causes a multisystem disorder with a variable phenotype due to heteroplasmy. Most carriers are oligosymptomatic with hearing loss and a variety of neurological and internal medical symptoms. Diabetes, cardiomyopathy and renal disease, which is newly reported here for this mutation, are frequent. The blood test is a reliable screening tool in affected families, but is of prognostic value only combined with examination of other tissues.

Biopsy↗

Effects of prostaglandins and indomethacin on gastric emptying in the rat.

Prostaglandins have been shown to stimulate contraction of gastrointestinal smooth muscle in vitro, and their synthesis has been reported in different gastrointestinal diseases. The aim of this study was to determine the different effects of PGs and indomethacin on gastric emptying in the rat in vivo, and to investigate their possible role as modulators of osmolarity induced changes in gastric emptying. Rats were fed via gastric tube with suspensions of various osmolarity containing different prostaglandins or indomethacin. Gastric emptying, measured by the quantity of food remaining in the stomach, was studied by a noninvasive technique using orally administered nonabsorbable marker 141Cerium. PGE2 given orally and its synthetic analogue 16-16-dimethyl PGE2 given subcutaneously caused significant delay of gastric emptying, while PGF2 alpha increased gastric emptying regardless of the administration route. Tube-feeding with high osmolarity suspension significantly reduced emptying rate of 141Cerium compared to feeding with low osmolarity suspension. Gastric emptying rate of the tracer was significantly higher in rats fed with low osmolarity test meal, in comparison to those fed with high osmolarity test meal. This effect was completely antagonized by indomethacin. Due to the known inhibitory effect of indomethacin on cyclooxygenase, the effects observed in the present study are also presumably mediated by the action of prostaglandins.

Animals↗

Impaired agglutination of IgM resulting from non-enzymatic glycation in diabetes mellitus.

Non-enzymatic glycation of circulating immunoglobulin G, A and M, measured by boronic acid affinity chromatography was found to be significantly increased in diabetes mellitus. The mean value of glycated IgM was already high in the control group: 49.58% (+/- 10.3% SD) and increased up to a mean value of 61.00% (+/- 8.5%) in the diabetic group. Similarly IgG and IgA glycation was significantly higher in the diabetic group than in controls: IgG 21.6% (+/- 3.4%) vs. 14.1% (+/- 2.9%; P less than 0.01); IgA 14.7% (+/- 4.9%) vs. 7.7% (+/- 1.3%; P less than 0.01). To investigate how glycation would alter IgM function, serum proportions from diabetic patients with blood group O were separated into glycated and non-glycated fractions by affinity chromatography and, adjusted to the same concentrations, tested against group A1 erythrocytes. Agglutination, which is mainly an IgM-mediated reaction, was significantly lower in the glycated than in the non-glycated fraction of IgM. The correlation between glycation of IgM and the reduction of agglutination titres in the glycated fraction was significant (r = 0.88, P less than 0.001). We conclude that impaired IgM function may be caused by non-enzymatic glycation in diabetes mellitus with possible consequences for host resistance in the early phase of infection.

Agglutination↗

Bioactivity and pharmacokinetics of human proinsulin in comparison to human insulin after intravenous and subcutaneous injection.

The hypoglycemic actions of human insulin (1 IU/kg b.w.) and biosynthetic human proinsulin in about equimolar amounts were studied after intravenous and subcutaneous injection in rabbits. Blood samples were taken up to four hours after injection for the determination of blood glucose and immunoreactive levels of both insulin and human C-peptide. For the determination of human C-peptide, serum taken after proinsulin injection was divided into two fractions. One was examined directly by the human C-peptide radioimmunoassay and the other after incubation with a protein-A-sepharose coupled insulin antibody to find "free human C-peptide". Proinsulin in amounts equimolar to 1 IU insulin/kg b.w., exerted a 34% stronger hypoglycemic action after subcutaneous injection than after intravenous administration (area under curve estimation). Proinsulin-induced hypoglycemia did not last longer after intravenous administration than that induced by intravenous insulin. Although subcutaneous proinsulin did not show the same maximum decrease of blood glucose compared to subcutaneous insulin, its action was significantly prolonged (up to 180 min). Specific measurement of free human C-peptide showed no evidence of conversion of proinsulin to insulin and C-peptide.

Animals↗