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Biomedical subjects

A E Meinders

Publications and source records attributed to A E Meinders.

At least 19 recordsLinked to original sources

Diurnal rhythm in anticoagulant effect of heparin during a low dose constant rate infusion. A study in healthy volunteers.

The objective of the study was to investigate possible diurnal rhythms in coagulation tests during a continuous intravenous infusion of unfractionated heparin. Six volunteers participated in the study, which was divided in a treatment (500 U heparin/h for 30 h) and a control experiment. Under basal conditions, no rhythm was found in coagulation tests. During heparin treatment, APTT, thrombin clotting time and anti-Xa activity showed a greater anticoagulant effect at night, with a striking decrease in the morning. In a search for the explanation of this phenomenon we looked for diurnal variations in the urinary excretion of heparin, in the plasma concentrations of antithrombin III and platelet factor 4, and in the effect of heparin added to the plasma samples in vitro. None of these studies provided the explanation.

Adult

[Pneumococcal pneumonia with a fulminant course].

Four patients admitted with a pneumococcal pneumonia are described. Well-known risk factors such as immunodeficiency or preexisting cardiopulmonary problems were absent. They had been ill for three to five days and had not been treated with antibiotics. Three patients died; upon admission these had extensive pulmonary infiltrates (two or more lobes affected), respiratory insufficiency necessitating mechanical ventilation, and shock at or soon after admission. The prognosis of pneumococcal pneumonia with a fulminant course has not improved in the last few decades despite proper antibiotics and intensive care treatment. Mortality is over fifty percent. Early recognition and treatment can contribute to a better prognosis.

Adult

Secretory diarrhea in villous adenoma of rectum: effect of treatment with somatostatin and indomethacin.

The effects of treatment with the synthetic long-acting somatostatin analogue SMS-201-995 were studied in a patient with a fluid and electrolyte secreting villous adenoma of the rectum. The effects of SMS-201-995 on rectal fluid volume and electrolyte loss, and local and general prostanoid production were compared with those of treatment with indomethacin. During treatment with the somatostatin analogue iso-osmolar rectal fluid production increased about 25%; the quantity of prostaglandin E2 in the rectal fluid rose almost 20-fold. Prostaglandin F2 alpha, 6-keto-prostaglandin F1 alpha and 13,14-dihydro-15-keto-prostaglandin F2 alpha output showed similar, though less impressive increments during somatostatin treatment. The somatostatin analogue did not affect urinary prostanoid excretion except for levels of 2,3-dinor-thromboxane B2, which doubled. With indomethacin treatment diurnal rectal fluid production dropped by about 50% and all prostanoids measured in urine and rectal fluid decreased below control values. It appears that the somatostatin analogue SMS-201-995 has a marked stimulatory effect on the in vivo prostanoid production by the villous adenoma. Perhaps this stimulation is not confined to the tumor only, but also affects thromboxane synthesis.

Adenoma

'Early' thyroid 123I uptake: correction for extrathyroidal neck radioactivity.

Should one correct for extrathyroidal neck radioactivity ('neck background') when interpreting perchlorate discharge test results? A new background correction method was developed using a linear probe. 123I produces photon peaks at two energy levels: 159 keV (gamma-rays) and 28 keV (X-rays), with an attenuation of 15 and 35% per cm water, respectively. If one fixes the position of the subject's neck, radiation from thyroid 123I produces an X/gamma detection ratio (alpha) which is constant and, due to the anterior localization of the thyroid, higher than the ratio (beta) produced by extrathyroidal 123I. These two ratios can be determined in vivo and used to calculate background-corrected and depth-corrected thyroid uptake. In simulation experiments our method was effective so long as the 'gland' was situated close enough to the 'neck' surface for the difference (alpha-beta) to be less than 0.19. Perchlorate discharge tests were performed in five euthyroid subjects who were pretreated with methimazole. The difference (alpha-beta) ranged from 0.27 to 0.36. Uncorrected, the mean discharge was 57% (range 47-66); corrected, it was 92% (range 88-94). In 15 hyperthyroid Graves' patients, with goitres varying from 13 to 63 ml, alpha-beta ranged from 0.22 to 0.40 and was unrelated to goitre size. The contribution of neck background is quantitatively important, especially when thyroid uptake is low; our new method corrects for it, even with large goitres.

Graves Disease

Exocrine pancreatic insufficiency and pancreatic fibrosis due to duodenal somatostatinoma in a patient with neurofibromatosis.

A case of duodenal somatostatinoma is described in a patient with Von Recklinghausen neurofibromatosis. The patient presented with exocrine pancreatic insufficiency, probably due to distal obstruction of the pancreatic duct by the tumor. Preoperative evaluation with calcium-pentagastrin and tolbutamide stimulation tests were nondiagnostic. At laparotomy, local excision of the tumor was performed. Pathological findings were compatible with duodenal somatostatinoma, causing pancreatic fibrosis. Somatostatin extracted from the tumor coeluted with the somatostatin-14 standard on high performance liquid chromatography (HPLC).

Adult

Preexisting cardiopulmonary disease attenuating the atrial natriuretic peptide response. Results in patients with acute respiratory failure.

The purpose of this study was to evaluate the pathophysiologic role of atrial natriuretic peptide (ANP) as a pulmonary artery vasodilator in patients with acute respiratory failure receiving artificial ventilation. Twenty-one consecutive patients were studied, 12 without and 9 with preexisting cardiopulmonary disease. Pulmonary artery plasma ANP levels were significantly higher than the levels obtained in the superior vena cava and radial artery. Plasma ANP levels correlated significantly with the plasma levels of its second messenger, guanosine 3',5'-cyclic monophosphate (cGMP). In the 12 patients without prior cardiopulmonary disease, plasma ANP levels correlated significantly with mean pulmonary arterial pressure (MPAP). This correlation was not found in the nine patients with preexisting cardiopulmonary disease. The cGMP/ANP ratio, indicating the biologic effect of ANP, was also higher in the patients without preexisting cardiopulmonary disease. These results are compatible with clearance and vasodilator activity of ANP in the pulmonary vascular bed, but only in patients without preexisting cardiopulmonary disease.

Acute Disease

Fibrinolytic system during long-distance running in IDDM patients and in healthy subjects.

OBJECTIVE: Endurance exercise has been advocated in diabetes mellitus to improve both metabolic control and prevent atherosclerotic complications. The response of the fibrinolytic system during prolonged exercise has not been studied in diabetes. RESEARCH DESIGN AND METHODS: In seven male marathon runners with IDDM and eight healthy nondiabetic male control subjects, matched for age and degree of training, we studied fibrinolytic and coagulation parameters during a 3-h 32-km outdoor running session. Measurements included t-PA, u-PA, PAI-1, PAP (as a measure of in vivo activation of fibrinolysis), FbDPs, FGN, vWF, and VIII:C. RESULTS: In both IDDM and control subjects, levels of t-PA, u-PA, PAP, vWF, and VIII:C continued to rise throughout the exercise, whereas PAI-1 showed a similar decline in both groups. FbDP rose slightly in both groups, and FGN remained unchanged. t-PA levels during exercise correlated closely with exercise intensity. These findings indicate that continued stimulation by exercise does not deplete endothelial PA stores. Differences between IDDM and control subjects were seen only for t-PA, vWF, and u-PA. The AUC during exercise (AUC0.5-3.0) of t-PA in IDDM was insignificantly lower than in control subjects (53 +/- 19 vs. 67 +/- 31 ng.ml-1.h), but the ratio of t-PA to exercise intensity was lower in IDDM (0.24 +/- 0.11 vs. 0.31 +/- 0.13, P less than 0.05). The AUC0.5-3.0 of vWF was lower in IDDM than in control subjects (569 +/- 268 vs. 880 +/- 265%.h, P less than 0.05). The AUC0.5-3.0 of u-PA was higher in IDDM than in control subjects (15.1 +/- 3.5 vs. 11.2 +/- 1.8 ng.ml-1.h, P less than 0.05). CONCLUSIONS: Despite a defect in the exercise-induced endothelial release of vWF and t-PA, the overall potential to activate fibrinolysis is intact in IDDM, possibly by enhancement of u-PA after exercise. Our data suggest that in IDDM, as in nondiabetic subjects, long-distance running may slow the progression of atherosclerosis by stimulating fibrinolysis.

Adult

Severe hypophosphatemia in a patient with anorexia nervosa during oral feeding.

We report a case of refeeding-associated hypophosphatemia in a 24-year-old malnourished male patient with anorexia nervosa but no history of alcoholism. He was given tube feeding with a low-calory preparation supplemented with phosphate. During refeeding, a severe hypophosphatemia developed after 5 days, i.e., serum phosphate 0.00-0.01 mmol/l for 2 days, accompanied by a reduction in red-cell ATP and 2,3-diphosphoglycerate, mild hemolytic anemia and transient changes in cardiac repolarization; there was, however, a striking lack of clinical symptomatology. Parenteral replacement with phosphate initially was complicated by an unexpected high urinary phosphate excretion due to an extremely low TmP/GFR (0.02 mmol/l) for over 2 days. Only after an increase of the TmP/GFR to supranormal values, i.e. up to 2.5 mmol/l, unrelated to changes in serum PTH or vitamin D3, the serum phosphate concentration became normal. The case report shows that severe hypophosphatemia can occur in nonalcoholic patients after oral feeding, and may induce reversible changes in renal phosphate handling that complicate replacement therapy.

Adult

Fluoxetine increases insulin action in obese nondiabetic and in obese non-insulin-dependent diabetic individuals.

Insulin resistance contributes to the metabolic defects in non-insulin-dependent diabetes mellitus (NIDDM). Anorectic agents have been shown to improve insulin action in NIDDM, irrespective of weight reduction. The serotonin-reuptake inhibiting agent fluoxetine has recently been recognized as an anorectic agent. The effect of fluoxetine on insulin action has not yet been determined. In a double blind placebo controlled crossover study, we examined hepatic and peripheral insulin action by the sequential hyperinsulinemic euglycemic clamp technique with infusion of 3-3H-glucose in eight obese NIDDM and in eight obese nondiabetics, matched for age, sex and body mass index. Body weight was kept constant. After 14 days of fluoxetine, 60 mg daily, in NIDDM half-maximal peripheral glucose uptake was achieved at a lower insulin level than after placebo (ED50pgu 180.5 +/- 25.8 vs 225.3 +/- 39.9 mU/l, P less than 0.05), but not in nondiabetics (140 +/- 15.3 vs 135.3 +/- 22.2 mU/l, n.s.). Maximal peripheral glucose uptake (Vmaxpgu) did not change significantly. Basal hepatic glucose production (HGP) was reduced after fluoxetine in both NIDDM (9.45 vs 10.37 mumol/kg/min) and in nondiabetics (8.57 vs 9.16 mumol/kg/min), although the difference was only significant in nondiabetics (P less than 0.05). Multivariate analysis disclosed no differences in the effect of fluoxetine between NIDDM and nondiabetics. When nondiabetics and NIDDM were considered together, only the most insulin-resistant individuals demonstrated a decrease in ED50pgu (P less than 0.001). Likewise, only the individuals with the most outspoken hepatic insulin resistance demonstrated a decrease in insulin level, at which hepatic glucose production is completely suppressed (HGP0) (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

C-Peptide

Fluoxetine increases insulin action in obese type II (non-insulin dependent) diabetic patients.

Insulin resistance contributes to the metabolic defects in non-insulin dependent diabetes mellitus (NIDDM). Anorectic agents have been shown to improve insulin action in NIDDM, irrespective of weight reduction. In a double-blind placebo-controlled cross-over study, we examined hepatic and peripheral insulin action by the sequential hyperinsulinaemic-euglycaemic clamp technique with infusion of 3-[3H]-glucose in eight obese NIDDM patients and in eight obese non-diabetics, matched for age, sex and body mass index. Body weight was kept constant. After 14 days of fluoxetine, 60 mg daily, in NIDDM half-maximal peripheral glucose uptake was achieved at a lower insulin level than after placebo (ED50pgu: 180.5 +/- 25.8 vs. 225.3 +/- 39.9 mU/l, P < 0.05), but not in non-diabetics (140 +/- 15.3 vs. 135.3 +/- 22.2 mU/l, n.s.). Maximal peripheral glucose uptake (Vmaxpgu) did not change significantly. Multivariate analysis disclosed no differences in the effect of fluoxetine between NIDDM and non-diabetics. When non-diabetics and NIDDM were considered together, only the most insulin-resistant individuals demonstrated a decrease in ED50pgu (P < 0.001). Likewise, only the individuals with the most outspoken hepatic insulin resistance demonstrated a decrease in insulin level, at which hepatic glucose production (HGP) is completely suppressed (HGP0) (P < 0.01). In conclusion, fluoxetine improves peripheral and hepatic insulin action in obese insulin-resistant subjects irrespective of its weight lowering effect.

Blood Glucose

Very low calorie diets and recently developed anti-obesity drugs for treating overweight in non-insulin dependent diabetics.

Weight reduction in non-insulin dependent diabetes mellitus (NIDDM) patients improves metabolic control, reduces cardiovascular risk factors, has blood pressure lowering effects and improves the well-being of the patient. This paper describes the role of very low calorie diets (VLCD), exercise, beta-adrenergic drugs and serotoninergic agents in the treatment of overweight in NIDDM. VLCD reduce body weight and improve glucose metabolism. Physical exercise programmes in addition to dietary restriction substantially contribute to weight loss and metabolic control in NIDDM. New specific beta-adrenergic agents, exhibiting virtually no beta 1 or beta 2 activity, increase energy expenditure and weight loss probably by enhancement of the basal metabolic rate. The target tissue in humans of this beta-adrenergic effect is as yet unknown. These drugs seem to enhance weight loss when used in combination with (very) low calorie diets compared to dietary restriction alone. Serotoninergic drugs reduce body weight by decreasing appetite, in particular for carbohydrates. Furthermore these drugs seem to improve insulin receptor sensitivity.

Adrenergic beta-Agonists

Effects of ACE inhibition on the course of nephropathy in type I diabetes mellitus.

Nephropathy is a severe complication of type I diabetes mellitus. About 25% of all new candidates for renal replacement therapy consist of diabetic patients. Glomerular hyperfiltration is an important causative factor in the development of this nephropathy. Microalbuminuria is the clinical first symptom of glomerular hypertension. New information stresses the importance of angiotensin II. Systemic as well as local reduction of angiotensin II formation can reduce glomerular hyperfiltration. Angiotensin-converting enzyme inhibitors should therefore be considered as first anti-hypertensive agents in type I diabetics with microalbuminuria.

Albuminuria

Tetrapolar body impedance is influenced by body posture and plasma sodium concentration.

Tetrapolar body impedance measures body resistance, which is highly correlated to total body water and fat-free mass. We investigated the change in resistance measured with tetrapolar impedance, resulting from fluid shifts, following an altered body posture and changes in resistance following an altered electrolyte composition of the extracellular fluid during hypertonic saline and mannitol infusion. An increase in body resistance was measured during recumbency, which was positively correlated with the calculated shift of interstitial fluid to the intravascular space. This effect was completely abolished after 5 min in the upright position. During infusion of 5% saline or 20% mannitol the change in resistance and the change in plasma sodium concentration were inversely correlated. Therefore the measurement of resistance is essentially influenced by alterations in the amount and composition of extracellular fluids. Using the resistance measurements standardization is obligatory for posture and plasma sodium concentration. This is particularly important when repeated measurements are performed.

Adult

Effect of serotonin re-uptake inhibition by fluoxetine on body weight and spontaneous food choice in obesity.

The effect of fluoxetine on body weight and spontaneous food choice was studied in twenty-three healthy, non-depressed, obese females on an outpatient basis. After a one week placebo run-in period, subjects were randomized to receive either fluoxetine (FXT) 60 mg daily (n = 11) or placebo (P) (n = 12) for 6 weeks in a double blind study design. BMI (35.2 +/- 0.8 vs 36.4 +/- 1.3 kg/m2, mean +/- s.e.m.) and age (38.1 +/- 239 vs 37.3 +/- 2.7 years) were not different in either group. No specific diet was prescribed. On four separate days per 14 days food records were collected. Data were analysed with the use of food composition tables. Statistical analysis was performed using Student's t test for independent samples for data on body weight and calorie intake. Macro-nutrient composition of the diet was analysed using multivariate analysis of variance and post hoc Student's t test for independent samples. All subjects lost weight during fluoxetine treatment. Mean (+/- s.e.m.) weight loss in the fluoxetine treated group was 3.6 +/- 0.5 kg, compared to a mean weight gain of 0.3 +/- 0.5 kg in the placebo treated group (P less than 0.001). In all patients food intake was reduced during fluoxetine treatment and this reduction could fully account for the observed weight loss. The mean total caloric intake per day was significantly lower during fluoxetine treatment compared with placebo (FXT 1123 +/- 118 kcal vs P 1845 +/- 87 kcal, P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult