Biomedical subjects

L Wouters

Publications and source records attributed to L Wouters.

At least 37 records · Page 2Linked to original sources

PubMed1994

Antitumoral effects of liarozole in androgen-dependent and independent R3327-Dunning prostate adenocarcinomas.

We examined the in vivo antitumoral effects of liarozole against androgen-dependent and independent Dunning rat prostatic tumors. Liarozole, applied as a dietary admixture, at a dose of 120 mg./100 gm. food, equivalent to 100 mg./kg. per day, inhibited the growth of the slow growing, well-differentiated, androgen-dependent Dunning-H tumor (median tumor volume decrease of 60%). At the same dose it also significantly reduced the growth of the androgen-independent, moderately differentiated PIF-1 (-60%) and androgen-independent, anaplastic AT-6 tumors (-73%). The growth of AT-6 sq tumor showing squamous metaplasia was unaffected by liarozole. When administered by oral gavage, liarozole at 40 (-82%) mg./kg. twice a day was as effective as castration (-92%) in reducing the androgen-dependent, poorly differentiated Dunning R3327-G tumor. Liarozole, administered by gavage, twice a day, also significantly reduced median tumor volume in the androgen-independent, AT-6 sq (-90% at 60 mg./kg., twice a day). This difference between liarozole administration by gavage and food admixture will have to be taken into account in further experimental studies. Inhibition of the growth of several androgen-dependent and, chiefly, androgen-independent Dunning prostate carcinoma sublines that differ widely in their histological degree of differentiation and growth rate suggests that liarozole may be a suitable agent for evaluation in second line treatment of hormone refractory prostate carcinoma in patients who relapse after androgen ablation.

Adenocarcinoma↗

PubMed1994

Deuterium dilution as a method for determining total body water: effect of test protocol and sampling time.

Deuterium dilution for the measurement of total body water (TBW) has been conducted using varying protocols for equilibration. We measured TBW from deuterium dilution in urine samples in twenty-eight subjects using three protocols: (1) early morning dosage without breakfast, measuring deuterium in a second voiding at 4 h and 6 h; (2) early morning dosage with breakfast with the same measurement times; (3) dosage as last consumption before overnight sleep, measuring deuterium in a second voiding at 10 h. Results were compared with TBW estimates from underwater weighing (UWW). Because UWW is an indirect measure of TBW, it is used as an independent reference method in order to compare only relative discrepancies between the two methods. TBW values in the fasted state were not significantly different from those obtained in the fed state. The urinary deuterium enrichment was higher at 4 h than at 6 h (resulting TBW differences: 0.6 (SD 0.4) l). At 4 h and 6 h, differences in TBW measurements from deuterium and densitometry were positively related to the amount of TBW, indicating incomplete equilibration in larger water compartments. At 10 h no such relationship existed, indicating complete mixing of deuterium. It is concluded that 10 h equilibration is preferable to the shorter 4 h and 6 h, for the determination of TBW.

Adult↗

PubMed1994

Validation of bioelectrical-impedance measurements as a method to estimate body-water compartments.

Single-frequency bioelectrical-impedance analyses (BIA) and bioelectrical spectroscopy (modeling multifrequency measurements; BIS) were validated as methods to predict body water (BW) compartments in 29 healthy adults. Total body water (TBW) and extracellular water (ECW) were determined by deuterium- and bromide-dilution techniques. Contribution of BIA to anthropometry and influence of the position of electrodes were examined. Stepwise-regression analysis revealed that inclusion of BIA to anthropometric data greatly improved the fit with BW compartments. Highly significant correlations were observed between BIS and BW compartments (TBW: r2 = 0.98, SEE = 1.2; ECW: r2 = 0.95, SEE = 0.6). Cross-correlation (14 males, and 15 females) indicated predictive potential of the method. Results from BIS and BIA were comparable, but it is argued that BIS has the potential of improved standardization of the method.

Adult↗

PubMed1994

Energy balance at high altitude of 6,542 m.

Weight loss due to malnutrition and possibly intestinal malabsorption is a well-known phenomenon in high-altitude climbers. Up to approximately 5,000 m, energy balance may be attained and intestinal energy digestibility remains normal. To see whether 1) energy balance may also be attained at 6,542 m and, if not, 2) whether decreased energy digestibility would play a significant role in the energy deficit, energy intake (EI), energy expenditure, body composition, and energy digestibility of 10 subjects (4 women, 6 men; 27-44 yr) were assessed during a 21-day sojourn on the summit of Mt. Sajama, Bolivia (6,542 m). EI was measured during two 3-day intervals: EI1 (days 7-9) and EI2 (days 17-19). Total fecal energy loss during EI1 was calculated from fecal energy measured by bomb calorimetry. Average daily metabolic rate (ADMR) at altitude was measured in six subjects (2 women, 4 men) using doubly labeled water over a 10-day interval (days 9-19). Basal metabolic rate was measured before and after the expedition by respiratory gas analysis. Body composition was estimated from skinfolds and body mass before and during the altitude sojourn. Subjects were in negative energy balance throughout the observation period (EI1-ADMR = -2.9 +/- 1.8 MJ/day and EI2-ADMR = -2.3 +/- 1.8 MJ/day based on a gross energy digestibility of 95%). The activity level, expressed as ADMR to basal metabolic rate, was 1.56-2.39. The loss of fat mass (3.7 +/- 1.5 kg) represented 74 +/- 15% of the loss of body mass.(ABSTRACT TRUNCATED AT 250 WORDS)

Acclimatization↗

PubMed1994

[A screening tool for depression in the elderly in the general population: the usefulness of Center for Epidemiological Studies Depression Scale (CES-D)].

In community-based studies the CES-D is the most widely used screening instrument for depression in the elderly. In the Netherlands it is relatively unknown. Results of a literature-survey and empirical data of three groups of older respondents in the Netherlands are presented (n1 = 224, n2 = 116, n3 = 190). To determine whether the CES-D can be used as a screening instrument for depression in the elderly in the Netherlands six criteria are formulated. The results of the literature-survey are favourable on most criteria. Because the overlap with symptoms of physical diseases is very limited, the CES-D can be used in physically ill populations. In our three groups of respondents the psychometric properties and practical use of the CES-D proved satisfactory (Cronbach's alfa 0.80-0.90 in three groups of respondents). Shortening the scale's answering-format has been advocated by others, but is discouraged. Being a screening instrument, the scale cannot be used as a substitute for psychiatric diagnosis. Recognising this limitation we conclude that the Dutch translation of the CES-D provides a useful instrument for measuring depressive symptoms in the elderly.

Aged↗

PubMed1993

Distribution of calcium in a subset of chronic hibernating myocardium in man.

The structural correlates of 'chronic hibernating myocardium' in man consist of myocardial cells which transformed from a functional state (rich in contractile material) to a surviving state (poor in contractile material, rich in glycogen). Since the calcium-handling organelles such as SR, sarcolemma and mitochondria underwent structural changes in cells so affected, the distribution of calcium was investigated in biopsies obtained from 'hibernating' areas. The material was processed for microscopic localization of total calcium (laser microprobe mass analysis, LAMMA) and of exchangeable calcium (phosphate-pyroantimonate precipitation method, PPA). Subcellular distribution of total calcium as assessed by LAMMA revealed that in the structurally affected cells the areas in which sarcomeres were replaced by glycogen contained significantly more calcium than all other areas probed such as mitochondria, remaining sarcomeres at the cell periphery and subcellular areas of normally structured cells. Calcium precipitate, obtained after PPA assessment, was localized at the sarcolemma but was virtually absent in the mitochondria of affected cells. The high calcium content in the myolytic areas of affected cells most probably belongs to a pool of bound calcium. The observations that calcium is retained at the sarcolemma and that mitochondria are devoid of precipitate favour the hypothesis that cells structurally affected as such are not ischaemic and are still able to regulate their calcium homeostasis.

Calcium↗

PubMed1993

Interplay between platelet-derived 5-hydroxytryptamine and arachidonic acid metabolites limits the thrombolytic efficacy of streptokinase against canine platelet-rich coronary thrombosis.

The comparative contributions of arachidonic acid (AA) metabolites and 5-hydroxytryptamine (5-HT) to the delay of reperfusion and rate of reocclusion after coronary thrombolysis with streptokinase were assessed in dogs using (a) single TXA2 synthase inhibition; (b) single 5-HT2-receptor blockade; (c) dual TXA2 synthase inhibition/PGH2 receptor antagonism; (d) 5-HT2-receptor blockade combined with TXA2 synthase inhibition; and (e) 5-HT2-receptor blockade combined with dual TXA2 synthase/PGH2-receptor antagonism. In open-chest anesthetized dogs, occluding coronary thrombi were induced by severe intimal injury in combination with critical artery stenosis. Fifty minutes after occlusive thrombus formation, the animals received intravenously (i) saline (S); (ii) ketanserin, 0.3 mg/kg (K), a 5-HT2-receptor antagonist; (iii) ridogrel, either at a low dose 0.3 mg/kg (R 0.3), exerting single TXA2 synthase inhibition; or (iv) at 5 mg/kg (R 5), exerting additional TXA2/PGH2-receptor antagonism; or (v) the combination of either dose of ridogrel with ketanserin. Ten minutes later, all dogs received streptokinase (SK; 1,000 IU/kg i.v. + 100 IU/kg/min i.v. infusion for 90 min). High-grade thrombolysis (> or = 50% coronary reperfusion vs. prethrombosis value as assessed by flow measurements) with SK occurred in 3/11 dogs treated with S, in 5/7 with R 0.3 and K, and in 7 of 7 dogs in the other medication groups; this occurred within > or = 55 min with S, R 0.3, and K, within 37 +/- 12 min with R 5 (p < 0.05 vs. solvent and R 0.3), and within 38 +/- 5 and 23 +/- 5 min with R 0.3 + K and R 5 + K, respectively (p < 0.05 vs. S, R 0.3, and K). The occurrence of reocclusion within 120 min after the cessation of SK administration was significantly reduced in all treatment groups, except K. That of cyclic flow reduction was reduced by R 5, R 0.3 + K, and R 5 + K. The peak extent of coronary reperfusion was highest in the K + R groups (S = 33% of preocclusion value; K = 60%; R 0.3 = 68%; R 5 = 76%; K + R 0.3 = 80%, p < 0.05 vs. S; and K + R 5 = 89%, p < 0.05 vs. solvent, R 0.3, and K). This study shows that the interplay between AA metabolites and 5-HT is involved in the platelet-dependent reduction in the thrombolytic efficacy of streptokinase in lysing coronary thrombi.

Animals↗

PubMed1993

Learning performance at different time periods after hypoxia in infant rats.

Infant rats were exposed to hypoxia. At different time periods after the hypoxic aggression the animals were subjected to a one-way active avoidance task consisting of 3 daily training sessions. Learning performance of hypoxic rats, expressed as the number of avoidances per 10 trials, was significantly decreased in all the sessions at posthypoxic day 35 (P < 0.001). The rate to which learning behaviour was affected by hypoxia was comparable among all 3 sessions in both groups. Histological evaluation of hippocampus and cortex at day 7 and day 35 after hypoxic exposure, did not reveal detectable structural changes. It can be concluded from this study that hypoxia, induced in 21 day old rats leads to learning performance deficits in the adult animal.

Animals↗

PubMed1992

Ridogrel inhibits systemic and renal formation of thromboxane A2 and antagonizes platelet thromboxane A2/prostaglandin endoperoxide receptors upon chronic administration to man.

The effects of ridogrel, a dual thromboxane A2 (TXA2) synthase inhibitor and TXA2/prostaglandin (PG) endoperoxide receptor antagonist, on systemic and renal production of prostaglandins and on platelet TXA2/PG endoperoxide receptors was evaluated upon chronic administration (300 mg b.i.d. orally, for 8 and 29 days) to man. Such a medication with ridogrel inhibits the systemic as well as the renal production of TXA2 as measured by the urinary excretion of 2,3-dinor-TXB2 and TXB2 respectively without inducing significant changes in systemic or renal PGI2 production. Simultaneously with the latter effects, the production of TXB2 by spontaneously coagulated whole blood ex vivo is inhibited (greater than 99%) while that of PGE2 and PGF2 alpha is largely increased. Administration of ridogrel causes a three- to five-fold shift to the right of concentration-response curves for U46619 in eliciting platelet aggregation; no tachyphylaxis is observed after 29 days of treatment in this respect. Apart from a reduction of serum uric acid levels with a concomitant increase in urinary uric acid excretion during the first days of treatment, no clinically significant changes in hematological, biochemical, hemodynamic and coagulation parameters occur during the 8 days or 29 days study. The study demonstrates that ridogrel is a potent inhibitor of the systemic as well as renal TXA2 synthase and an antagonist of platelet TXA2/PG endoperoxide receptor in man, covering full activity during 24 h at steady-state plasma level conditions without tachyphylaxis during 29 days of medication. The compound is well tolerated, at least during 1 month of administration.

Adult↗

PubMed1992

Diet-induced thermogenesis and cumulative food intake curves as a function of familiarity with food and dietary restraint in humans.

Cumulative food intake curves and diet-induced thermogenesis were recorded in women during four-course solid-food lunches, consisting of familiar and unfamiliar food, offered in ad lib or restricted portions, in order to assess a possible relation between eating behaviour on the one hand and a reflection of internal processes and subject characteristics on the other. The subjects were characterized as normal weight restrained, normal weight unrestrained, and overweight restrained. A negative relation was found between degree of restraint and deceleration of the cumulative food intake curve during the ad lib courses of any menu, and between degree of restraint and diet-induced thermogenesis (p less than 0.001). Consequently, a positive relation was found between deceleration of the cumulative food intake curves during the ad lib courses of any menu and diet-induced thermogenesis (p less than 0.001). Diet-induced thermogenesis during the first serving of a meal consisting of unfamiliar food was significantly higher in all groups than during the other two times, when meals consisting of more familiar food were served (+0.98%; 0.71%, p less than 0.05).

Adult↗

PubMed1992

Accuracy of estimates of forthcoming ingestion as a function of menu familiarity and dietary restraint.

Estimates of forthcoming intake were compared with amount eaten in women who were normal-weight restrained eaters, unrestrained eaters or overweight restrained eaters, for three four-course lunches of which the first consisted mainly of an Italian menu, the second and third mainly a Japanese menu. The differences between estimated and eaten amounts for the first and third lunch correlated negatively with degree of restraint. This indicates that those who score high on dietary restraint have learnt better ways of estimating their intake. No relation was found between the difference in estimated and eaten amount and degree of restraint during the second lunch. This indicates that the unfamiliarity of a meal makes it more difficult to predict how much of it would be satiating.

Adult↗

PubMed1992

Prevalence of psychopathology in drug-addicted Dutch.

In Dutch samples of treated heroin addicts, high prevalences of a heterogeneous psychiatric co-morbidity can be found with regard to Diagnostic and Statistical Manual (third edition) (DSM-III) classifications, Zung Depression Inventory, and sum scores of a 90-item Symptom Checklist (SCL-90). A high-threshold (N = 87) and a low-threshold (N = 116) program are compared with regard to psychopathology and severity of psychopathology. A consecutive admissions design was used. More than 50% of the respondents suffered from a lifetime DSM-III Axis I disorder (70% with antisocial personality disorder included), and 40% were still suffering from one of the disorders in the year preceding the interview. Schizophrenia was diagnosed five times as much as in normal population samples (5%). The most frequently diagnosed disorders were recurrent major depression, phobic disorders, alcohol abuse and dependence, dysthymic disorder, and antisocial personality disorder. The prevalences of DSM-III disorders, the total number of symptoms, and the score on the Zung Depression Inventory and 90-item Symptom Checklist were all significantly higher in treatment-seeking drug addicts entering the high-threshold program. Within each program, three clinically meaningful subgroups can be distinguished: one group with DSM-III Axis I lifetime or current psychopathology and/or antisocial personality disorder, one with antisocial personality disorder only, and one with neither DSM-III psychopathology nor antisocial personality disorder. Possibly, self-selection results in patients with more serious conditions entering more treatment-oriented facilities. Odds ratios show that schizophrenia and mood disorders and especially associated on a lifetime and current basis.

Adult↗

PubMed1992

Levamisole plus 5-fluorouracil inhibits the growth of human colorectal xenografts in nude mice.

Fragments of human colorectal adenocarcinomas were inserted under the renal capsule of nude mice. The growth of these tumour grafts was significantly inhibited by the combination of 5-fluorouracil (5-FU) and levamisole. An alternating regimen of levamisole 2.5 mg/kg and 5-FU 20 mg/kg decreased the size of tumour implants by 33-59% and/or increased the number of macroscopically disappeared fragments in the combined group compared with ineffective monotherapy with saline, levamisole or 5-FU. This model could be valuable for investigating the mechanism of action of levamisole and to evaluate the effects of this adjuvant therapy in other oncological settings.

Adenocarcinoma↗

PubMed1992

Fat-free mass as a function of fat mass and habitual activity level.

The best predictor of energy expenditure in man is the fat-free mass of the body. Fat-free mass explains most of the variation in resting metabolic rate and even in total metabolic rate under sedentary conditions. We studied possible determinants of fat-free mass as routes to influence energy metabolism. Existing data sets were analysed with observations on height, fat mass (FM), fat-free mass (FFM), and habitual level of physical activity (PA). PA was calculated from average daily metabolic rate (ADMR) as measured over 1-4-week intervals with 2H2(18)O and basal metabolic rate (BMR): PA = ADMR/BMR. Ninety-six subjects, 66 females and 30 males, from 7 different studies were included. FFM and FM were adjusted for height by taking its ratio to the square of height, in analogy with the body mass index. Subsequently, all analyses were corrected for origin of the data. In a regression analysis FM explained 53 and 40% of the variation in FFM in females and males, respectively. Adding PA to the model raised the explained variation in FFM in females to 62%. In contrast with females (r = 0.10, n.s.), there was an independent relationship between PA and FM in males (r = -0.41, p less than or equal to 0.05), such that a higher PA was related to a lower FM. In conclusion, FFM is a function of FM and PA. The absence of an effect of exercise training on FFM, i.e. additional exercise in weight-reduction programmes, is discussed.

Adipose Tissue↗

PubMed1991

Oversensitivity to serotonin of the collateralized vascular bed in rat hindquarters: mechanisms of increased vasoconstriction.

A buffered solution was perfused at a constant flow rate (2 ml/min) through both iliac arteries in rat hindquarters. Perfusion pressures were measured in normal and collateralized vascular beds of the left and right hind-leg, respectively. Bolus injections of various agonists produced concentration-dependent increases in perfusion pressure in both collateralized and normal circulatory beds. Serotonin, in particular, and noradrenaline, to a lesser extent, produced more pronounced vasoconstriction on the collateral side than on the normal side. The difference in vasoreactivity to serotonin was related to a difference in both vascular structure and sensitivity of both types of vascular bed. Vasoconstriction induced by serotonin was inhibited by 5-HT2 antagonists. Selective blockade of alpha 1,alpha 2,beta 1-beta 2 adrenoceptors and amine uptake blockade were ineffective. This study indicates that, in rat hind-legs, the collateralized vascular bed is superreactive to serotonin in comparison with the normal bed. This resetting of reactivity to serotonin is due to the specific vascular structure as well as to an increased 5-HT2 receptor-mediated sensitivity.

Animals↗

PubMed1991

Restrained eating, obesity, and cumulative food intake curves during four-course meals.

A four-course meal was presented to six obese and 18 normal weight women in which the second course was eaten ad libitum and the other three courses were fixed in amount. Eating behaviour was observed directly and intake was monitored via an electronic scale built into the table under the plate. Intake deceleration was observed in the normal weight women who scored low on the Herman-Polivy (1980) restraint questionnaire and on the cognitive restraint factor (F1) of Stunkard and Messick's (1985) questionnaire, whereas the normal weight and obese restrained women displayed linear cumulative food intake. In all groups, if deceleration occurred in the second course it was usually identical in the third and fourth courses, and constant eating rate persisted from the second course to the later courses. Food-specific eating rates were positively correlated to relative palatability, and removed deviation from linearity in cumulative intake over the four courses.

Body Mass Index↗

PubMed1991

Aortofemoral dacron reconstruction for aorto-iliac occlusive disease: a 25-year survey.

The authors present a consecutive series of 869 patients, who received an aorto(bi)femoral Dacron graft for occlusive disease between 1963 and 1988. The operative indications were grade 1 disease (n = 371), grade 2 disease (n = 408) or grade 3 disease (n = 90). The operative mortality was 4.5% and remained stable over the years of the study. The median survival was 8.2 years and 25% of the patients survived for more than 15 years. Late patency decreased to 74% and 70% after 10 and 15 years, respectively. Fifty-six patients underwent a major amputation in the long run. The amputation rate increased to 3, 8.6 and 12.1%, respectively for grade 1, grade 2 and grade 3 disease. Satisfactory functional results were obtained by 51% and 40% of the patients after 10 and 15 years, respectively. By means of secondary and tertiary operations this increased to 70% and 61%. Long term functional results were primarily dependent on smoking habits postoperatively, the date of operation and the presence of concomitant femoro-popliteal occlusive disease.

Amputation, Surgical↗

PubMed1991

Evaluation of factors influencing myocardial infarct size in unconscious dogs.

STUDY OBJECTIVE: The aim was to evaluate the factors determining myocardial infarct size in unconscious dogs. DESIGN: In anaesthetised open chest dogs, the left anterior descending coronary artery was occluded either by ligation or by thrombosis for different time periods (1.5 h, 4 h, 24 h), with or without reperfusion. Haemodynamic variables were recorded throughout the experiment. Radioactive microspheres (15 microns) were injected at the end of the ischaemic period to measure regional myocardial blood flow. Infarct size and area at risk were determined by the Evans blue triphenyltetrazolium staining technique followed by planimetry. SUBJECTS: Mongrel dogs of either sex (n = 16-42 per experiment), weight 18-25 kg, were used. MEASUREMENTS AND MAIN RESULTS: A large interindividual variability in infarct size was observed after occlusion of the left anterior descending coronary artery at a standardised location for a well defined period. An examination of the factors responsible for this variability was carried out in order to develop a statistical model which would make it possible to predict infarct size. Using multiple regression analysis, it was found that in most protocols (except 90 min thrombosis) more than 85% of the variability in infarct size could be explained by the size of the area at risk and the amount of collateral flow. Thus, knowing the area at risk and the collateral flow, a fairly accurate prediction can be made of the size of the infarct that the dog will develop after a defined occlusion period. Furthermore, it was found that the infarct size increased with duration of occlusion, while duration of reperfusion had no effect. In the 90 min occlusion group thrombosis induced a larger final infarct than ligature. CONCLUSIONS: A correction for baseline variables is necessary in order to compare infarct size between experimental groups. The usefulness of this procedure is shown by an example of an experimental intervention, i.e., R 56,865, a drug with known cardioprotective effects.

Animals↗