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Biomedical subjects

A E Meinders

Publications and source records attributed to A E Meinders.

At least 55 records · Page 3Linked to original sources
PubMed2001

Pathogenesis of malignant ascites: Starling's law of capillary hemodynamics revisited.

Peritonitis carcinomatosa, indicating the presence of malignant cells in the peritoneal cavity, is a well-known complication of malignant disease. As a result, so-called malignant ascites develops. Malignant ascites is a debilitating condition for which no effective anti-tumor therapy is available. Frequent draining may be necessary to relieve pain and discomfort. Most studies regarding malignant ascites focus on diagnosis and treatment. In this paper. we will address the subject from a pathophysiologic perspective, using the characteristics of malignant ascites, Starling's equation of capillary forces, and recent knowledge regarding biologically active peptides produced by tumor cells. Following this approach. apart from decreased lymphatic ascites absorption, increased net capillary fluid-production can be identified as a contributing feature of ascites formation. The increased net filtration is due to an increase of overall capillary membrane-surface, increased capillary permeability and a subsequent increase of intraperitoneal protein concentration leading to increased intraperitoneal oncotic pressure. This sequence might be the result of biologically active peptides produced by tumor cells such as vascular endothelial growth factor and basic fibroblast growth factor. Interference with these mediators may serve as a target in future therapeutic strategies.

Ascites↗
PubMed2001

Sympathovagal imbalance in hyperthyroidism.

We assessed sympathovagal balance in thyrotoxicosis. Fourteen patients with Graves' hyperthyroidism were studied before and after 7 days of treatment with propranolol (40 mg 3 times a day) and in the euthyroid state. Data were compared with those obtained in a group of age-, sex-, and weight-matched controls. Autonomic inputs to the heart were assessed by power spectral analysis of heart rate variability. Systemic exposure to sympathetic neurohormones was estimated on the basis of 24-h urinary catecholamine excretion. The spectral power in the high-frequency domain was considerably reduced in hyperthyroid patients, indicating diminished vagal inputs to the heart. Increased heart rate and mid-frequency/high-frequency power ratio in the presence of reduced total spectral power and increased urinary catecholamine excretion strongly suggest enhanced sympathetic inputs in thyrotoxicosis. All abnormal features of autonomic balance were completely restored to normal in the euthyroid state. beta-Adrenoceptor antagonism reduced heart rate in hyperthyroid patients but did not significantly affect heart rate variability or catecholamine excretion. This is in keeping with the concept of a joint disruption of sympathetic and vagal inputs to the heart underlying changes in heart rate variability. Thus thyrotoxicosis is characterized by profound sympathovagal imbalance, brought about by increased sympathetic activity in the presence of diminished vagal tone.

Adult↗
PubMed2001

Renal clearance of endogenous leptin in hypertensive humans with or without renal artery stenosis.

In humans, the kidney is involved in leptin clearance from the body. The present study was performed to assess the renal extraction of leptin in hypertensive patients with or without renal artery stenosis. Sixty-five hypertensive subjects (39 males and 26 females) underwent catheterization of the renal artery and both renal veins with blood sampling for measuring leptin levels. Blood flow to both kidneys was measured by the xenon washout technique. From these data, renal leptin uptake and renal fractional extraction of leptin were calculated. Endogenous creatinine clearance ranged from 24 to 191 ml/min in the males and from 20 to 149 ml/min in the females. In 25 patients, radiological signs of renal artery stenosis were present. Total renal leptin uptake by both kidneys averaged 141 +/- 47 ng x min(-1) x 100 g(-1). No differences in leptin uptake were found between males and females or between patients with or without renal artery stenosis. The average renal extraction fraction of leptin was 6 +/- 2%. Renal leptin uptake and renal extraction fraction of leptin did not correlate with arterial leptin concentrations or with blood pressure, endogenous creatinine clearance, or the presence or absence of renal artery stenosis. In hypertensive patients with or without renal artery stenosis, the kidney removes only a small fraction of circulating leptin from the body within one passage. This fraction remains relatively constant despite wide variations in renal function or circulating leptin.

Adolescent↗
PubMed2001

Estimation of growth hormone secretion rate: impact of kinetic assumptions intrinsic to the analytical approach.

We compared four common mathematical techniques to determine daily endogenous growth hormone (GH) secretion rates from diurnal plasma GH concentration profiles in 24 women (16 upper- or lower-body obese and 8 normal-weight individuals). Two forms of deconvolution analysis and two techniques based on a priori determined GH clearance estimates were employed. Deconvolution analyses revealed significant differences in the 24-h GH secretion rate between normal-weight and upper-body obese women, whereas the other two techniques did not. Moreover, deconvolution analyses predicted that the reduction in mean plasma GH concentrations in upper-body obese women was accounted for by impaired GH secretion, whereas the other methods suggested that obesity increases GH metabolic clearance. Thus we infer that disparate conclusions concerning GH secretion can be drawn from the same primary data set. The different inferences likely reflect dissimilar kinetic assumptions and the particular limitations intrinsic to each analytical approach. Accordingly, we urge caution in the facile comparison of calculated GH secretion data in humans, especially when kinetic and secretion measurements are performed under different conditions. The most appropriate way to determine the GH secretion rate in humans must be balanced by the exact intent of the experiment and the acceptability of different assumptions in that context.

Adult↗
PubMed2001

Altered neuroregulation of GH secretion in viscerally obese premenopausal women.

We used deconvolution analysis of 24-h plasma GH concentration profiles (10- min sampling intervals) to appraise GH secretion rates and elimination kinetics in obese (body mass index, approximately 34 kg/m2) premenopausal women with large visceral fat area (LVFA; n = 8) vs. small visceral fat area (SVFA; n = 8) as determined by magnetic resonance imaging. The subjects were matched for body mass index, body fat percentage, and age. The impact of the loss of 50% of prestudy weight excess induced by caloric restriction was assessed as well. The results were compared with those obtained in normal weight control women (n = 8). LVFA subjects manifested markedly (4-fold) reduced mean plasma GH levels, which was brought about by jointly diminished basal and pulsatile GH secretion. Moreover, visceral obesity was associated with loss of regularity of GH release, as established by the approximate entropy statistic. In contrast, SVFA subjects produced normal daily amounts of GH and exhibited mean 24-h plasma GH concentrations that were similar to those in normal weight controls. GH half-life and distribution volume were not different among the study groups. Importantly, weight loss did not affect the daily GH secretion rate in LVFA women, so that their mean plasma GH concentration remained considerably reduced (approximately 50%) compared with controls (despite the loss of approximately 40% of visceral fat). Normal GH kinetics in SVFA women were not significantly influenced by weight reduction. Thus, GH neuroregulation appears to be particularly altered in obese women with a tendency to store fat in their visceral adipose depot. Because weight loss did not reverse GH secretion rate in viscerally obese women, we speculate that relative hyposomatotropism is a primary feature of these women, which could be involved in their tendency to preferentially store excess fat in visceral adipose tissue.

Adipose Tissue↗
PubMed2001

Food choice in hyperthyroidism: potential influence of the autonomic nervous system and brain serotonin precursor availability.

We explored energy and macronutrient intake in patients with Graves' hyperthyroidism. We specifically hypothesized that hyperthyroidism is associated with increased appetite for carbohydrates, because of enhanced sympathetic tone and diminished serotonin mediated neurotransmission in the brain. To test this hypothesis, we measured food intake by dietary history and food selected for lunch in the laboratory in 14 patients with Graves' hyperthyroidism. Twenty-four-hour catecholamine excretion was used as a measure of activity of the sympathetic nervous system (SNS) and the plasma [Trp]/[NAA] ratio was measured to estimate (rate limiting) precursor availability for brain 5-hydroxytryptamine synthesis. All measurements were repeated after the subjects had been treated to establish euthyroidism. In addition, the effects of nonselective beta-adrenoceptor blockade upon these parameters were studied to evaluate the influence of beta-adrenergic hyperactivity on food intake. Hyperthyroidism was marked by increased SNS activity and reduced plasma [Trp]/[NAA] ratio. Accordingly, energy intake was considerably and significantly increased in hyper vs. euthyroidism, which was fully attributable to enhanced carbohydrate consumption, as protein and fat intake were not affected. These results suggest that hyperthyroidism alters the neurophysiology of food intake regulation. Increased SNS activity and reduced Trp precursor availability for 5-hydroxytryptamine synthesis in the brain may drive the marked hyperphagia and craving for carbohydrates that appears to characterize hyperthyroid patients. Because propranolol did not affect food intake in hyperthyroidism, the potential effect of catecholamines on food intake might be mediated by alpha-adrenoceptors.

Autonomic Nervous System↗
PubMed2001

Monitoring renal function in obese patients with type 2 diabetes mellitus in daily practice.

BACKGROUND: Endogenous creatinine clearance (GFR(24-hr)) and the Cockcroft formula (GFR(Cockcroft)) are used for the assessment of the glomerular filtration rate (GFR) in daily practice. The influence of extreme obesity in Type 2 diabetes mellitus (T2DM) on the Cockcroft formula was evaluated. METHODS: We compared GFR as calculated by GFR(Cockcroft) to GFR as determined by GFR(24-hr) in 210 patients with T2DM and normal serum creatinine levels. The influence of body mass index (BMI) on the difference between both methods was evaluated. RESULTS: GFR(Cockcroft) was an overall good predictor for GFR(24-hr), but a large individual difference between both methods was observed. A significant correlation was found between the two methods (r=0.962, p<0.001). In T2DM patients with a BMI>35 kg/m2, mean GFR(Cockcroft) was 18% greater than GFR(24-hr). For every unit BMI in this patient group the GFR(Cockcroft) increased by 7.9% relative to the GFR(24-hr). CONCLUSIONS: The major limitation of this evaluation is the lack of a gold standard for GFR measurement. This evaluation of daily practice shows the GFR estimation by the Cockcroft formula and the 24-hr creatinine clearance are in agreement, although a large individual variation was found between both methods making the interchangeability questionable. In view of the influence of BMI on the Cockcroft formula, this should not be used to estimate the GFR in T2DM patients with extreme obesity.

Body Mass Index↗
PubMed2000

[Patient with eosinophilic polymyositis].

In a 36-year-old patient with a severe polymyositis peripheral eosinophilia and abundant infiltration of muscle tissue by eosinophilic granulocytes were observed. Eosinophilic polymyositis was diagnosed. Treatment consisted of high dose prednisone, immunoglobulin and azathioprine, resulting in complete remission of the disease. Idiopathic eosinophilic polymyositis is an uncommon disorder, first described in 1976. The eosinophilic granulocyte is essential in the pathogenesis (by releasing toxic mediators and the production of cytokines), but the cause of the activation is still unknown. Treatment is aimed at immune suppression and consists first of all in administration of prednisone.

Adult↗
PubMed2000

[Role of the morning report in the training of internists].

The morning report constitutes an important part of the daily routine in the Department of Internal Medicine. According to the literature, this procedure makes an effective contribution to the training of internists, provided that a number of conditions are fulfilled (a critical but not hostile atmosphere, broad participation, a large number of patients). We compared the diseases discussed in the morning report retrospectively with the final attainment levels for the training of internists as described in the recently published 'Outline of Internal Medicine'. Of the diseases described in this outline, almost two-thirds (62.4%) had been discussed on the morning report within a period of 6 months. The morning report would seem to be an important addition to the other forms of knowledge transfer within the training of internists.

Academic Medical Centers↗
PubMed2000

[Very-low-calorie diet in treatment of morbidly obese patient with diabetes mellitus type 2].

A 40-year-old woman with type 2 diabetes mellitus, hypertension, central obesity (body mass index: 40 kg/m2) and mixed hyperlipidaemia was treated with oral hypoglycaemic, antihypertensive and hypolipidaemic drugs as well as with intramuscular insulin. She kept gaining weight and developed hiatus hernia with regurgitation. Treatment was changed to a very low caloric diet during 9 months. She lost 18 kg of body weight and all drugs could be discontinued, as she became normoglycaemic, normotensive and normolipidaemic. Obesity is a risk factor for insulin resistance and type 2 diabetes mellitus. To reach euglycaemia in overweight type 2 diabetics is a difficult task. Oral hypoglycaemic agents and insulin are often used in combination with dietary intervention without adequate results. Losing body weight should be first-line treatment. However, compliance with weight-reducing methods is often low. The pathophysiologic importance of significant weight loss in the treatment of (morbid) obesity in type 2 diabetic patients is great.

Adult↗
PubMed2000

Relationships between volume and pressure measurements and stroke volume in critically ill patients.

OBJECTIVE: To evaluate the relationships between the changes in stroke volume index (SVI), measured in both the aorta and the pulmonary artery, and the changes in intrathoracic blood volume index (ITBVI), as well as the relationship between changes in aortic SVI and changes in the pulmonary artery wedge pressure (PAWP). DESIGN: Prospective study with measurements at predetermined intervals. SETTING: Medical intensive care unit of a university hospital. PATIENTS AND METHODS: One hundred and fifty-four measurements were taken in 45 critically ill patients with varying underlying disorders. Aortic SVI and pulmonary arterial SVI were determined with thermodilution. PAWP was measured using a pulmonary artery catheter. ITBVI was determined with thermal-dye dilution, using a commercially available computer system. RESULTS: A good correlation was found between changes in ITBVI and changes in aortic SVI. However, this correlation weakened when changes in ITBVI were plotted against changes in pulmonary arterial SVI, which was in part probably due to mathematical coupling between ITBVI and aortic SVI. A good correlation between changes in ITBVI and changes in aortic SVI could also be established in most of the individual patients. No correlation was found between changes in PAWP and changes in aortic SVI. CONCLUSION: ITBVI seems to be a better predictor of SVI than PAWP. ITBVI may be more suitable than PAWP for assessing cardiac filling in clinical practice.

Aorta↗
PubMed2000

[Heat stroke: pathophysiology and pathogenesis].

The pathophysiology of heat stroke is not fully understood. Endotoxins and cytokines appear to play a major part in the central nervous system and in the peripheral tissues. Use of specific receptor blockers prior to heat exposure can diminish cerebral damage in animal experiments. The energy depletion model of Hubbard gives a possible explanation for the rhabdomyolysis observed in some heat stroke patients. Failure of the ATP dependent Na(+)-K+ pump is essential in this theory.

Acute Kidney Injury↗
PubMed2000

Extravascular lung water in patients with septic shock during a fluid regimen guided by cardiac index.

BACKGROUND: To elucidate whether patients with a septic shock develop pulmonary edema in a treatment protocol in which volume loading is guided by its effect on the cardiac output, rather than by preset values of pulmonary artery wedge pressure (PAWP). METHODS: 15 consecutive patients with the diagnosis of septic shock were studied in a prospective observational study. Cardiac output, PAWP and extravascular lung water index (EVLWI) were determined at regular intervals during the first 24 h of treatment. Fluid challenges were given if MAP was <80 mm Hg and/or CI was <4.5 l/min/m(2), and PAWP was <16 mm Hg. Further fluid challenges were only given if the preceding fluid challenge resulted in an increase in CI of more than 10% and PAWP was still <16 mm Hg. RESULTS: EVLWI was slightly above normal (10.4+/-1.2 ml/kg) and did not change during the treatment protocol. One third of the patients had an initial PAWP>16 mmHg. In these patients, EVLWI was significantly higher than in patients with an initial PAWP <16 mm Hg (14.1+/-1.1 ml/kg versus 10.0+/-0.9 ml/kg, P=0.026). No significant correlation was found between PAWP and EVLWI. CONCLUSION: In this study, patients with septic shock did not develop pulmonary edema during the first 24 h of treatment, when their fluid regimen was guided by the effects on cardiac output.

Adult↗
PubMed2000

Weight loss, weight maintenance, and improved cardiovascular risk factors after 2 years treatment with orlistat for obesity. European Orlistat Obesity Study Group.

OBJECTIVE: To determine the effect of orlistat, a new lipase inhibitor, on long-term weight loss, to determine the extent to which orlistat treatment minimizes weight regain in a second year of treatment, and to assess the effects of orlistat on obesity-related risk factors. RESEARCH METHODS AND PROCEDURES: This was a 2-year, multicenter, randomized, double-blind, placebo-controlled study. Obese patients (body mass index 28 to 43 kg/m2) were randomized to placebo or orlistat (60 or 120 mg) three times a day, combined with a hypocaloric diet during the first year and a weight maintenance diet in the second year of treatment to prevent weight regain. Changes in body weight, lipid profile, glycemic control, blood pressure, quality of life, safety, and tolerability were measured. RESULTS: Orlistat-treated patients lost significantly more weight (p<0.001) than placebo-treated patients after Year 1 (6.6%, 8.6%, and 9.7% for the placebo, and orlistat 60 mg and 120 mg groups, respectively). During the second year, orlistat therapy produced less weight regain than placebo (p = 0.005 for orlistat 60 mg; p<0.001 for orlistat 120 mg). Several obesity-related risk factors improved significantly more with orlistat treatment than with placebo. Orlistat was generally well tolerated and only 6% of orlistat-treated patients withdrew because of adverse events. Orlistat leads to predictable gastrointestinal effects related to its mode of action, which were generally mild, transient, and self-limiting and usually occurred early during treatment. DISCUSSION: Orlistat administered for 2 years promotes weight loss and minimizes weight regain. Additionally, orlistat therapy improves lipid profile, blood pressure, and quality of life.

Adult↗
PubMed1999

Pulmonary artery wedge pressure and extravascular lung water in patients with acute cardiogenic pulmonary edema requiring mechanical ventilation.

This study describe the values of pulmonary artery wedge pressure (PAWP) and the extravascular lung water (EVLW) index in patients with acute cardiogenic pulmonary edema who require mechanical ventilation. Ten consecutive patients with acute cardiogenic pulmonary edema who required mechanical ventilation were studied. Cardiac index was determined with thermodilution. Central venous pressure and PAWP were measured with a pulmonary artery catheter. EVLW index was determined with the thermal dye dilution technique, using a commercially available computer system. Measurements were made at regular preset intervals after the initiation of mechanical ventilation. PAWP was normal at baseline (11.6+/-0.9 mm Hg, range 8 to 17) and did not change. EVLW index was elevated at baseline (13.7+/-1.5 ml/ kg) and decreased to a normal value after 24 hours (8.6+/-1.2 ml/kg, p = 0.02). Concomitantly cardiac index increased from 2.61+/-0.24 to 3.61+/-0.14 L/min/m2 (p = 0.05). There was no correlation between PAWP and EVLW index. Fluid balance was +1,221+/-908 ml after 24 hours and there was a weight gain of 0.88+/-1.06 kg after 24 hours. Thus, patients with acute cardiogenic pulmonary edema requiring mechanical ventilation may have a normal PAWP after mechanical ventilation has been initiated. In a hemodynamic unstable situation, these patients may require fluid challenges to improve cardiac output, despite the presence of pulmonary edema. The pulmonary edema, measured as EVLW index, resolves rapidly when cardiac performance improves, despite positive fluid balances and weight gain in the first 24 hours.

Acute Disease↗
PubMed1999

The design of a prospective study of Pravastatin in the Elderly at Risk (PROSPER). PROSPER Study Group. PROspective Study of Pravastatin in the Elderly at Risk.

The PROspective Study of Pravastatin in the Elderly at Risk (PROSPER) is a randomized, double-blind, placebo-controlled trial designed to test the hypothesis that treatment with pravastatin will diminish risk of subsequent major vascular events in a cohort of men and women (70 to 82 years old) with preexisting vascular disease or significant risk of developing this condition. Five thousand eight hundred four men and women in addition to receiving advice on diet and smoking, have been randomized equally to treatment with 40 mg pravastatin/day or matching placebo in 3 centers (Cork, Ireland, Glasgow, Scotland, and Leiden, The Netherlands). Following an average 3.5-year intervention period, a primary assessment will be made of the influence of this therapy on major vascular events (a combination of coronary heart disease, death, nonfatal myocardial infarction, and fatal and nonfatal stroke). A number of additional analyses will also be conducted on the individual components of the primary end point, on men, on women, and on subjects with and without previous evidence of vascular disease. Finally, an assessment will be made of the effects of treatment on cognitive function, disability, hospitalization or institutionalization, vascular mortality, and all-cause mortality.

Aged↗