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Biomedical subjects

M Frölich

Publications and source records attributed to M Frölich.

At least 55 records · Page 3Linked to original sources
PubMed2000

Effect of modified sham feeding and insulin-induced hypoglycemia on function of the proximal stomach.

BACKGROUND/AIM: Animal experiments have shown that vagal cholinergic stimulation causes an increase in proximal gastric tone, but little is known about the effect of vagal stimulation on proximal gastric motor function in humans. Vagal cholinergic stimulation can be elicited by modified sham feeding (MSF) or by insulin-induced hypoglycemia. The aim of our study was to investigate the effect of MSF and insulin-induced hypoglycemia on the motor and sensory function of the proximal stomach in humans. METHODS: Eight healthy volunteers participated in random order in three experiments: (A) control experiment, (B) MSF and (C) intravenous insulin injection. Intragastric volume was recorded with a barostat set at a constant preselected pressure level (MDP + 2 mm Hg). Pancreatic polypeptide (PP) secretion was measured as an indicator of cholinergic tone. RESULTS: PP secretion increased significantly after both MSF (p<0.05) and insulin administration (p<0.01). No changes in intragastric volume were seen after MSF, while intragastric volume increased significantly in response to insulin-induced hypoglycemia when compared to control (290+/-43 vs. 148+/-24 ml; p<0.01). No differences in perception scores were seen between the three experiments. CONCLUSIONS: Vagal cholinergic stimulation by MSF has no effect on the motor function of the proximal stomach, while insulin-induced hypoglycemia causes a relaxation of the proximal stomach.

Adult↗
PubMed2000

C-reactive protein is a strong but nonspecific risk factor of fatal stroke in elderly persons.

An elevated level of C-reactive protein is a strong predictor of cardiovascular events in elderly persons. Whether C-reactive protein has direct adverse vascular effects or is a marker of aspecific systemic inflammation remains to be determined. The aim of this study was to investigate the relation between C-reactive protein and the occurrence of fatal strokes in elderly persons. In the Leiden 85-Plus Study, a population-based prospective follow-up study, we studied the levels of C-reactive protein in 80 participants who died from stroke within the first 5 years of follow-up. Levels of C-reactive protein were determined in serum samples at baseline. Levels of C-reactive protein were also determined in 82 control subjects who survived for the first 5 years of follow-up and in 83 participants who died from noncardiovascular causes. Mortality risks were estimated with logistic regression and adjusted for differences in age, sex, smoking, medication, total cholesterol, history of diabetes or hypertension, and previous cardiovascular events. Levels of C-reactive protein at baseline were 2-fold higher in subjects who died from stroke than in control subjects (median 5.7 versus 2.7 mg/L, P<0.005). The levels of C-reactive protein in subjects who died from stroke or from noncardiovascular causes were similar (median 5.7 versus 4.9 mg/L, P=0.7). The risk of death from stroke as well as from noncardiovascular causes increased linearly up to 10-fold in subjects with the highest levels of C-reactive protein at baseline (P<0.001). The levels of C-reactive protein were lower when more time had elapsed between blood sampling and time of death during follow-up (P=0.01). C-reactive protein is a strong but nonspecific risk factor of fatal stroke in old persons. The data do not support the idea that C-reactive protein has direct vascular effects that underlie fatal cerebrovascular disease.

Aged↗
PubMed2000

A switch from oral (2 mg/day) to transdermal (50 microg/day) 17beta-estradiol therapy increases serum insulin-like growth factor-I levels in recombinant human growth hormone (GH)-substituted women with GH deficiency.

The response to GH therapy in adults with GH deficiency (GHD) is considerably variable. Generally, the response with regard to serum insulin-like growth factor (IGF)-I concentrations is significantly lower in females compared with males with GHD, which could at least partly be explained by the use of oral estrogen replacement therapy. In the present study, we investigated whether a switch from oral to transdermal estrogen therapy alters serum IGF-I concentrations in women with GHD on stable GH therapy. Six females with GHD and LH deficiency were investigated. During cycles 1 and 2, an oral dose of estradiol was given (2 mg/day), whereas during cycles 3, 4, and 5 estradiol was administered via the transdermal route at a dose of 50 microg/day. Serum estrone levels significantly decreased (2470+/-475 to 110+/-26 pmol/L, P = 0.005), serum sex hormone-binding globulin levels significantly decreased (102+/-13 to 63+/-7 nmol/L, P = 0.004), and serum estradiol levels also decreased albeit nonsignificantly with transdermal therapy (273+/-81 to 114+/-18, P = 0.083). Serum IGF-I levels significantly increased after the switch from oral to transdermal estrogen therapy (18.7+/-1.6 and 23.4+/-2.5 nmol/L, respectively, P = 0.008). Two of the six patients experienced fluid retention-related side effects, which disappeared after a reduction in dose at the end of the study. The results of the present study suggest that the potency of GH is altered in patients on transdermal compared to oral estradiol therapy. Further investigation should be undertaken to answer the question whether the increase in serum IGF-I levels is due to lower serum levels of estradiol or to differences in the mode of administration of estradiol.

Administration, Cutaneous↗
PubMed2000

Apparently complete restoration of normal daily adrenocorticotropin, cortisol, growth hormone, and prolactin secretory dynamics in adults with Cushing's disease after clinically successful transsphenoidal adenomectomy.

ACTH production in Cushing's disease is characterized by a markedly elevated rate of basal (nonpulsatile) secretion, an increased mass of ACTH released per burst and an unremarkable pulse frequency. In addition, the ACTH secretory process and that of GH and PRL exhibit profoundly disordered patterns. Whether some or all of these disturbances can be reversed or normalized by transsphenoidal microadenomectomy remains unknown. We therefore investigated the detailed dynamics of ACTH, GH, and PRL in eight patients (aged 38.9+/-4.2 yr) with pituitary-dependent Cushing's disease who were in long-term (8.2+/-1.7 yr) clinical remission following transsphenoidal surgery and eight controls matched for age, gender, and body mass index. To this end, blood was sampled at 10-min intervals for 24 h for the later assay of ACTH, cortisol, GH, and PRL. Secretory activity was quantitated by deconvolution methods, and the pattern orderliness (regularity) of hormone release was determined by the approximate entropy (ApEn) statistic. The joint synchrony of ACTH and cortisol secretion was monitored by the cognate bivariate statistic, cross-ApEn. Diurnal properties of the hormonal release were appraised by cosinor analysis. Based on deconvolution analysis, postsurgical patients exhibited a normal frequency, half-life, duration, and mass of ACTH and cortisol secretory bursts. Accordingly, the 24-h production rates of both ACTH (2.5+/-0.7 microg/L in patients vs. 2.9+/-0.7 microg/L in controls; P = 0.755) and cortisol (49+/-11 micromol/L in patients vs. 73+/-15 micromol/L in controls; P = 0.217) were normal also. The acrophase of the diurnal rhythm of ACTH (patients, 0817 h +/- 37 min; controls, 0850 h +/- 38 min; P = 0.629) and cortisol (patients, 1000 h +/- 24 min; controls, 0855 h +/- 30 min; P = 0.175) was also restored by surgery. ApEn values of ACTH (patients, 1.168 +/- 0.090; controls, 0.864+/-0.122; P = 0.133) and cross-ApEn of ACTH-cortisol (patients, 1.396+/-0.087; controls, 1.170+/-0.076; P = 0.140) secretion were both normal in this cohort, denoting restoration of the secretory process regularity. Cortisol ApEn was slightly higher in patients (patients, 1.034+/-0.084; controls, 0.831+/-0.038; P = 0.048). Both GH and PRL time series manifested full reconstitution of pulsatile, 24-h rhythmic, and entropic properties. In summary, clinically successful transsphenoidal microadenomectomy in adults with Cushing's disease can fully normalize virtually all quantitative features of regulated ACTH, cortisol, GH, and PRL secretion. Further studies will be needed to establish the consistency of these findings in larger cohorts of adults with Cushing's disease and in children with this disorder and to delineate the significance, if any, of a residual, minimally detectable disruption of orderly cortisol secretion in this patient population.

Adenoma↗
PubMed1999

The relative contribution of insulin secretory capacity, insulin action, and incretins to metabolic control after islet transplantation in dogs.

Adequate metabolic control is central to the concept of islet transplantation, but has received limited attention. We studied metabolic control in 8 dogs at 6-9 months after intrasplenic autografting of approximately 25% of the normal mass islets--as compared to 30 controls. A similar posttransplant reduction to approximately 25% of the insulin secretory capacity as assessed by intravenous arginine stimulation during 35 mM glucose clamps, mirrored the reduction of the islet mass. Postprandially, in contrast, the insulin response had increased to 140% in the islet recipients--with a concomitant rise of glycemia to approximately 8.5 mM. Posttransplant, the insulin secretory capacity correlated both with the index of insulin action (which averaged 55% of the normal value) as assessed by euglycemic hyperinsulinemic clamps, and--inverse--with the postprandial glucose excursions. Because insulin action did not correlate with postprandial glucose, the insulin secretory capacity appears to be the primary determinant of the impaired glucose tolerance. Marked postprandial hyperglucagonemia, and a virtually absent pancreatic polypeptide response in the grafted animals, may also have contributed to the impaired glucose tolerance. Posttransplant, infusion of a physiological dose of the gut hormone glucagon-like peptide-1 during 8.5 mM glucose clamps--mimicking the postprandial glycemia--potentiated glucose-stimulated insulin 175%. Thus, after transplantation of a suboptimal islet mass, postprandial glucose excursions are restrained by hyperglycemic potentiation of the entero-insular axis, which may account for the difference in the insulin response to the intravenous and oral challenges. Because, the insulin secretory capacity reflects the islet mass and appears to be the major determinant of glucoregulation, transplantation of a larger islet mass may allow near-normal glycemic control.

Animals↗
PubMed1999

Changes in circulating atrial natriuretic peptide in relation to the cardiac status of Rhesus monkeys after total-body irradiation.

PURPOSE: In order to determine the presence of cardiac damage associated with total-body irradiation (TBI), both echocardiographic parameters and circulating levels of atrial natriuretic peptide (ANP) were measured in three different age-cohorts of Rhesus monkeys (Macaca mulatta) previously treated with TBI without additional chemotherapy, at post irradiation intervals up to 30 years, at the former TNO/Radiobiological Institute at Rijswijk. MATERIALS AND METHODS: Standard echocardiographic techniques were used to measure cardiac dimensions and left ventricular function in situ. Plasma-ANP concentration was measured by radioimmunoassay (RIA). After necropsy, tissue samples from the heart were taken for histological analysis. RESULTS: Plasma-ANP levels of animals which received TBI were significantly (P = 0.0005) elevated when compared to age-matched controls (66.4 +/- 8.4 vs. 33.1 +/- 5.7 ng/l). Moreover, a positive correlation (P = 0.032) between plasma-ANP values and time post treatment was found in the TBI group. TBI affected cardiac dimensions; however, no significant differences in cardiac functional parameters were observed between the different treatment groups. Necropsy reports demonstrated slight but consistent cardiovascular damage in several animals treated with TBI, in terms of increased incidence of mild epicardial and coronary arterial wall fibrosis, compared to age-matched controls. CONCLUSIONS: The concentration of plasma-ANP proved to be an important parameter for subclinical cardiac damage. In humans, serial determinations of plasma ANP in individual patients might provide relevant information about the cardiac status after TBI.

Animals↗
PubMed1999

Acute hyperglycaemia in the forearm induces vasodilation that is not modified by hyperinsulinaemia.

OBJECTIVE: To evaluate whether acute elevations of local plasma glucose concentrations could influence forearm blood flow (FBF) and how this interacts with local hyperinsulinaemia in healthy volunteers. METHODS: Using the perfused forearm technique, in random order, glucose 20% or saline 0.9% as a control was infused in three dose steps (0.3, 1.0, and 3.0 ml/min) for 5 min each in eight healthy men. The infusion experiments were repeated, in random order, during local hyperinsulinaemia by intra-arterial infusion of insulin 0.05 mU/kg/min. The ratio of FBF of the infused over the FBF in the control arm (FR) was measured at 15-sec intervals during the infusions. RESULTS: Glucose infusion increased the FR dose-dependently by 172%+/-39% (M+/-SE) at the highest dose (P < 0.01). During hyperinsulinaemia the glucose-induced increase in FR was significantly (P < 0.01) less, 96%+/-26%, however, when changes in FR or forearm vascular resistance were related to the plasma glucose concentrations both glucose infusions were equipotent. The saline infusions induced small increases in FR of 27+/-5% (P < 0.01) and 24+/-11% (P > 0.05), without or with insulin respectively. The changes in FR during the saline infusions were much smaller than during the glucose infusions (P < 0.01). During the glucose infusions small but significant increases in FBF and venous plasma glucose in the non-infused forearm appeared, indicating carry-over effect and the possibility of a very low threshold for glucose-induced vascular effects. CONCLUSIONS: High, local levels of glucose in the forearm have a vasodilator effect on resistance vessels in skeletal muscle of the forearm that is not modified by local hyperinsulinaemia. Indications were found that the threshold for this glucose-induced vasodilation may be remarkably low, but this needs to be studied more formally.

Acute Disease↗
PubMed1999

The absorption profile and availability of a physiological subcutaneously administered dose of recombinant human growth hormone (GH) in adults with GH deficiency.

AIMS: To investigate the absorption profile and estimate the bioavailability of three doses of recombinant human growth hormone (rhGH) smaller than 2 IU in females with GH deficiency (GHD). A second aim of the study was to compare the mean 24 h GH concentrations after s.c. injection of rhGH with the physiological mean 24 h GH concentration of healthy females of comparable age, height, and BMI. METHODS: Fourteen female patients with substituted GHD, and 14 healthy females of comparable age, height, and BMI were studied. All GHD patients underwent 24 h GH sampling after s.c. injection of rhGH in doses of 0.6, 1.2, or 1.8 IU. In addition, these patients underwent a 4 h GH sampling after i.v. injection of rhGH (1 IU). In healthy subjects, blood was withdrawn every 10 min for 24 h to determine the physiological GH profile. RESULTS: A s.c. dose of 0.6 IU resulted in a mean and maximum GH concentration of 0.95+/-0.04 mU l(-1) and 2.62+/-0.09 mU l(-1). A doubling (or tripling) of the rhGH dose resulted in a doubling (or tripling) of the mean and maximum GH concentration. The time of maximum GH concentration was reached on average after 261+/-27 min. Mean GH concentration in healthy females was comparable with the mean GH concentration after a s.c. dose of 1.2 IU. Mean availability of the s.c. injected dose was 63%+/-4%. CONCLUSIONS: A dose of 1.2 IU resulted in a mean GH concentration comparable with the mean physiological GH concentration in healthy females of comparable age, height, and BMI.

Absorption↗
PubMed1999

The prevalence of subclinical hypothyroidism at different total plasma cholesterol levels in middle aged men and women: a need for case-finding?

OBJECTIVE: In order to determine whether screening of thyroid function is justified in patients with hypercholesterolaemia, we determined the prevalence of subclinical hypothyroidism at different levels of total plasma cholesterol in middle-aged men and women. DESIGN AND METHODS: 1200 participants were selected from a population based cross sectional study on risk factors for cardiovascular diseases. The participants were divided into three groups: total plasma cholesterol < 5 mmol/l, total plasma cholesterol 5-8 mmol/l, total plasma cholesterol > 8 mmol/l. Each group was comparable in size and sex distribution. Subclinical hypothyroidism was defined as plasma TSH levels higher than 4 mU/l, in the presence of normal free thyroxine (FT4(4)) concentration. RESULTS: Plasma samples of a total of 1191 participants were analyzed. The overall prevalence of subclinical hypothyroidism was 1.9% in men and 7.6% in women of middle age. In women the prevalence of subclinical hypothyroidism increased from 4.0 percent in the lowest, to 10.3 percent in the highest cholesterol stratum (P = 0.02). In men, the mean prevalence was 1.8 percent and roughly similar in the various strata. After age correction, an increase of 1 mU/l TSH in women was associated with an increase of 0.09 mmol/l total plasma cholesterol (95% confidence interval (CI) 0.02-0.16 mmol/l). A similar trend was found in men (0.16 mmol/l, 95% CI -0.02-0.34 mmol/l). CONCLUSIONS: In the population, the prevalence of subclinical hypothyroidism is up to 10 percent in middle aged women with high levels of total plasma cholesterol and may justify case-finding. In these women approximately 0.5 mmol/l of total plasma cholesterol can be attributed to the subclinical thyroid dysfunction. In men a similar correlation between thyroid dysfunction and total plasma cholesterol is seen, but the prevalence of thyroid dysfunction is considerably lower.

Cholesterol↗
PubMed1999

Does jejunal feeding activate exocrine pancreatic secretion?

BACKGROUND: The upper small bowel is of pivotal importance for the stimulation of exocrine pancreatic secretion in response to a meal. We hypothesize that more distal delivery of nutrients into the small intestine will result in less activation of pancreatic secretion. MATERIALS AND METHODS: Eight healthy subjects (3 male, 5 female; age 23 +/- 1 years) participated in two experiments, performed in random order. Subjects were intubated with a 4-lumen tube. Duodenal outputs of pancreatic enzymes and bilirubin were measured by aspiration using a recovery marker. The distal opening was used for continuous administration of a mixed liquid meal and located at either the ligament of Treitz or 60 cm further distally. Gallbladder volume was measured and blood samples were drawn for determination of gastrointestinal hormones. The duration of each experiment was 4 h; with 1 h fasting and 3 h continuous administration of nutrients. RESULTS: During proximal jejunal feeding, pancreatic enzyme output increased significantly over basal levels. No significant increase over basal levels was observed during distal jejunal feeding. Bilirubin output and gallbladder contraction were significantly (P < 0.05) reduced during distal compared to proximal jejunal feeding. No significant differences were found in plasma levels of CCK, PYY and neurotensin between proximal and distal jejunal feeding. CONCLUSION: Continuous feeding in the distal jejunum does not stimulate exocrine pancreatic secretion but maintains gallbladder contraction, although to a lesser extent. These effects are not related to hormonal changes but probably reduced activation of the enteropancreatic reflexes.

Adult↗
PubMed1999

Serum leptin levels are not influenced by physical training in type 2 diabetes mellitus patients.

AIM: To investigate the effect of physical training on leptin levels in elderly, obese patients with type 2 diabetes mellitus. METHODS: Twenty men and 38 women with type 2 diabetes mellitus with a body mass index (BMI) of > 25 kg/m2 participated in a prospective randomized study. Patients were either on oral glucose lowering drugs (n = 39) or insulin therapy (n = 19). Physical training consisted of a guided, standardized, 6-week training programme performed in the hospital on a cyclo ergometer followed by a 6-week period of guided training at home and ended in a 12-week period of training at home without supervision. Clinical data and laboratory samples including fasting insulin and leptin levels and maximal aerobic capacity were assessed at the start of the study and at 6 and 26 weeks thereafter. RESULTS: Physical training resulted in significantly positive changes in maximal aerobic capacity (VO2max) and maximum work load. No effects of physical training on serum leptin levels and insulin concentrations were detected. Leptin levels were strongly correlated with body mass index (r = 0.63), body fat content (r = 0.61), and fasting insulin concentrations (r = 0.38). Women had threefold higher leptin levels than men. No differences in leptin levels between patients on insulin therapy and patients on oral glucose lowering drugs were found. CONCLUSIONS: No effect of physical training on leptin levels was detectable in elderly, obese type 2 diabetes mellitus patients.

Aged↗
PubMed1999

Influence of obesity and body fat distribution on growth hormone kinetics in humans.

We studied the kinetics of exogenous recombinant 22-kDa human growth hormone (rhGH) in premenopausal women with upper body obesity (UBO), lower body obesity (LBO), or normal body weight. A bolus of 100 mU rhGH was administered during a continuous infusion of somatostatin to suppress endogenous GH secretion. GH kinetics were investigated with noncompartmental analysis of plasma GH curves. GH peak values in response to GH infusion and plasma half-life of GH were not significantly different between normal weight and obese subjects. In contrast, GH clearance was 33% higher in LBO women and 51% higher in UBO women compared with clearance in normal weight controls. The difference in clearance between LBO and UBO was not statistically significant. Altered GH clearance characteristics contribute to low circulating GH levels in obese humans. Body fat distribution does not appear to affect GH kinetics.

Adipose Tissue↗
PubMed1999

Increased episodic release and disorderliness of prolactin secretion in both micro- and macroprolactinomas.

To quantify prolactin (PRL) secretion patterns, ten untreated (female) microprolactinoma patients and six (male) macroprolactinoma patients underwent repetitive blood sampling every 10 min over 24 h. PRL release activity was analyzed from plasma PRL concentration (immunofluorimetric assay) profiles via a model-independent discrete peak detection program (Cluster) and a waveform-independent deconvolution technique (Pulse). Diurnal variations were analyzed by cosinor analysis. The number of distinct PRL pulses (mean +/- S.E.M.) was increased in patients: microprolactinoma 18.6 +/- 0.6/24 h versus female controls 12.4 +/- 0.6 (P = 6.7 x 10-s), and macroprolactinoma 18.0 +/- 0.9 versus male controls 13.5 +/- 0.8/24 h (P = 0.003). In patients, PRL pulse height, amplitude, pulse area and interpeak nadir concentrations were each greatly elevated compared with gender-matched controls. By 2-component deconvolution analysis, the mean nadir PRL secretion rate in microprolactinoma patients was augmented 20-fold at 0.408 +/- 0.089 microgram/l per min versus in female controls 0.019 +/- 0.009 microgram/l per min (P < 0.001); and in macroprolactinoma by 130-fold at 2.067 +/- 0.693 micrograms/l per min versus male controls 0.016 +/- 0.001 microgram/l per min (P = 0.001). Corresponding 24 h mean PRL secretion rates were in women, 0.658 +/- 0.147 and 0.044 +/- 0.018 (P < 0.001), and in men, 3.309 +/- 1.156 and 0.035 +/- 0.010 micrograms/l per min (P = 0.001), being respectively 15- and 94-fold increased in tumors. The estimated PRL production per day was 160 +/- 15 and 187 +/- 20 micrograms in male and female controls respectively. PRL production was 2860 +/- 640 micrograms in female patients with microadenomas (P < 0.001), and 37,800 +/- 5900 micrograms in male macroadenoma patients (P = 0.001). Cosinor analysis of the plasma concentrations revealed a significant rhythm in nine of ten, patients with a microadenoma, and in five of six with a macroadenoma. The same method applied to pulse height and amplitude disclosed a significant rhythm for PRL pulse height, but not for pulse amplitude, suggesting preserved rhythmicity of baseline interpulse nadir PRL concentrations. Approximate entropy (ApEn), a scale- and model-independent regularity statistic, averaged 1.6559 +/- 0.028 in microprolactinoma patients versus 0.8128 +/- 0.079 in female controls (P = 1.7 x 10(-8)); ApEn in macroadenomas was 1.5674 +/- 0.054 versus male controls 0.8773 +/- 0.076 (P = 1.7 x 10(-5), signifying greater secretory irregularity in the patients. Compared with microadenomas, macroadenomas exhibited a higher mean plasma concentration, overall mean PRL secretion rate, nadir secretion rate and pulse area, but similar peak frequency. We conclude that PRL secretion by prolactinomas is characterized by increased plasma PRL episodicity of release, increased total (15- to 100-fold) and basal (20- to 130-fold) secretion rates, and increased disorderlines of minute-to-minute secretion. These abnormalities of secretory control are very similar to those for GH and ACTH identified earlier in acromegaly and Cushing's disease respectively, thus suggesting mechanistic generality of pituitary tumor secretory derangements, independent of the particular hormone.

Adult↗
PubMed1999

Effect of danaparoid sodium on proteinuria, von Willebrand factor, and hard exudates in patients with diabetes mellitus type 2.

In diabetic nephropathy, heparan sulfate glycosaminoglycan side chains are reduced in glomerular basement membranes proportionally to the degree of proteinuria. Recently, it was demonstrated that additional therapy with danaparoid sodium, a mixture of sulfated glycosaminoglycans with mainly heparan sulfate, lowered proteinuria in type 1 diabetes patients with diabetic nephropathy. A randomized placebo-controlled parallel study was performed with 750 anti-Xa units of danaparoid sodium once daily in type 2 diabetes patients with severe proteinuria. The aim of the study was to evaluate the possible effects of danaparoid sodium on proteinuria, endothelial dysfunction, and hard exudates in the retina and to determine the safety/tolerability of this drug. Twenty-two patients completed the study, and one patient had to stop prematurely after 6 wk of danaparoid sodium treatment because of urticaria at the injection sites. Apart from a small decrease of hemoglobin and minor skin hematomas at the injection site in five patients in the danaparoid sodium group, no other safety parameters showed any clinically or statistically significant difference between and within groups. The relative change in time of both the urinary albumin and protein excretion rate corrected for creatinine did not differ between both treatment arms (P = 0.2 and 0.49, respectively). No retinal complications or changes of hard exudates occurred. von Willebrand factor was elevated in both groups, but was not influenced by either treatment modality. Contrary to the beneficial effects that occurred in type 1 diabetes patients with diabetic nephropathy, treatment for 8 wk with 750 anti-Xa units of danaparoid sodium gave no reduction of proteinuria, hard exudates, and von Willebrand factor.

Adult↗
PubMed1998

Anti-inflammatory cytokine profile and mortality in febrile patients.

BACKGROUND: An anti-inflammatory cytokine profile on whole-blood stimulation in vitro is associated with fatal outcome of meningococcal disease. We investigated whether an anti-inflammatory cytokine profile in the circulation is associated with adverse outcome in other infectious diseases. METHODS: We enrolled 464 consecutive patients (272 men, 192 women) who presented to hospital with fever (> or = 38.2 degrees C). On admission we measured plasma interleukin 10 (IL-10) and tumour necrosis factor alpha (TNF alpha), and collected clinical and microbiological data on the febrile illness, then followed up all patients for clinical outcome. FINDINGS: In at least 399 of the 464 patients fever was caused by infection. 33 patients died after a median hospital stay of 11 days (interquartile range 3-20). Concentrations of IL-10 were significantly higher in non-survivors (median 169 pg/mL [IQR 83-530]) than in survivors (median 88 pg/mL [42-235], p=0.042). When dichotomised around the median, the mortality risk was two times higher in patients who had high concentrations of IL-10 than in those with low concentrations (relative risk 2.39 [95% CI 1.07-5.33]), in patients with low and high concentrations of TNF alpha. In the 406 patients without haemodynamic deterioration in the first 24 h, IL-10 was higher and TNF alpha lower in patients who died than in those who survived. The ratio of IL-10 to TNF alpha was higher in non-survivors (median 6.9 [3.0-21.0]) than in survivors (median 3.9 [2.0-7.0], p=0.040). This ratio was highest in patients who died without underlying disease (median 21.5 [5.0-25.0]). Age, sex, and duration of fever before admission did not explain the differences in IL-10 and TNF alpha. INTERPRETATION: An anti-inflammatory cytokine profile of a high ratio of IL-10 to TNF alpha is associated with fatal outcome in febrile patients with community-acquired infection. Our findings caution against a widespread use of proinflammatory cytokine inhibition in patients with sepsis.

Adolescent↗
PubMed1998

Effect of insulin on basal and cholecystokinin-stimulated gallbladder motility in humans.

BACKGROUND/AIMS: Acute hyperglycemia inhibits gallbladder contraction. In non-diabetic subjects this inhibitory effect may result from endogenous hyperinsulinemia. Therefore we investigated the effects of acute hyperglycemia and euglycemic hyperinsulinemia on basal and cholecystokinin-stimulated gallbladder motility. METHODS: Gallbladder volume (ultrasonography) and duodenal bilirubin output were studied simultaneously in nine healthy volunteers (age 20-52 years) on 3 separate occasions in random order during: (a) saline infusion (control), (b) hyperglycemic hyperinsulinemic clamping (HG; plasma glucose at 15 mmol/l), and (c) euglycemic hyperinsulinemic clamping (HI; plasma insulin at 150 mU/l, glucose at 4-5 mmol/l). After a 2-h basal clamp period, cholecystokinin was infused intravenously for 60 min at 0.25 IDU x kg(-1) x h(-1), followed by another 60 min at 0.5 IDU x kg(-1) x h(-1). RESULTS: HI and HG significantly (p<0.05) reduced basal duodenal bilirubin output compared to control, while basal gallbladder volume did not change. At the low dose cholecystokinin, gallbladder emptying during HG (25+/-3%) and HI (39+/-4%) was significantly (p<0.01) reduced compared to control (61+/-4%). The inhibitory effect of HG was significantly (p<0.05) stronger compared to HI. Duodenal bilirubin output during the low dose cholecystokinin was significantly (p<0.05) reduced by HG, but not by HI. No inhibitory effect of HG and HI on gallbladder emptying and duodenal bilirubin output was observed with the high dose of cholecystokinin. CONCLUSIONS: In healthy subjects acute hyperglycemia and euglycemic hyperinsulinemia reduce basal duodenal bilirubin output and inhibit gallbladder emptying stimulated by low dose cholecystokinin. These results suggest that insulin is involved in the inhibitory effect of hyperglycemia on basal and cholecystokinin-stimulated gallbladder motility.

Adult↗