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Biomedical subjects

H Pijl

Publications and source records attributed to H Pijl.

At least 55 records · Page 3Linked to original sources
PubMed1997

Predictors of weight loss during treatment with d-fenfluramine.

OBJECTIVE: To identify parameters predictive of weight loss during treatment with d-fenfluramine. This may provide a tool to recognize patients who are sensitive to the weight-reducing effect of d-fenfluramine and thus prevent unnecessary prescription. DESIGN: An open intervention study during which biweekly control visits were scheduled. The study lasted 12 weeks. SETTING: The General Internal Medicine outpatient clinic of the Leiden University Hospital. Patients were recruited through a newspaper advertisement. SUBJECTS: Forty-eight healthy, obese patients (36 women and 12 men), aged 39 +/- 10 years (mean +/- SD) with a body mass index of 34.3 +/- 4.1 kg/m2 enrolled. INTERVENTIONS: d-Fenfluramine 15 mg twice daily for 12 weeks. MAIN OUTCOME MEASURES: Body weight, height, waist and hip circumference, food intake, smoking habits, obesity history, treatment history, family history of obesity and compliance with the medication scheme were recorded as potential predictors of weight loss. RESULTS: One patient was withdrawn because of depressive symptoms. Thirteen patients did not lose weight. On average, the other 34 patients lost 5.7 +/- 2.9 kg or 18.1 +/- 9.4% of excess body weight. High compliance with the drug regimen was associated with a twofold greater weight loss (17.7 +/- 12.3 vs. 9.0 +/- 9.4% of excess weight, ANOVA, P = 0.0088). Patients with a positive family history of obesity lost twice as much weight as patients without obese relatives (15.8 +/- 11.8 vs. 6.0 +/- 7.3% of excess weight; ANOVA, P = 0.0078). No other potential determinants were predictive for weight loss. CONCLUSIONS: Informing patients that compliance with the medication scheme improves treatment outcome will be useful. Previous failures to lose weight should not exclude patients from treatment. A positive family history of obesity needs further evaluation as a possible determinant of weight loss in forthcoming studies.

Adult↗
PubMed1996

Borderline personality, impulsiveness, and platelet monoamine measures in bulimia nervosa and recurrent suicidal behavior.

This study examined the relationship between borderline and impulsive personality traits on the one hand, and monoamine function on the other in 15 women with bulimia nervosa and 15 women with recurrent suicidal behavior. Platelet serotonin (5-HT) and platelet monoamine oxidase (MAO) activity were used as peripheral measures of monoaminergic function. All suicide attempters were diagnosed as having a borderline personality disorder, whereas this diagnosis was less frequent in bulimics. Bulimics with borderline comorbidity resembled recurrent suicide attempters with borderline personality disorder more closely in both psychological (anger, impulsive behavior) and biochemical characteristics (platelet 5-HT) than bulimics without borderline personality disorder. Platelet 5-HT was higher in patients with borderline personality than in normal female controls and was positively correlated with the disposition to experience anger. Impulsive personality traits were consistently negatively correlated with platelet MAO activity. Our findings support the subdivision of bulimics according to the presence of borderline or "multi-impulsive" personality disorder.

Blood Platelets↗
PubMed1996

Leptin.

A highly conserved protein called 'leptin' was recently discovered to play a role in regulation of the energy balance in humans and rodents. This 167-amino-acid-containing protein is only produced and secreted by mature adipocytes. Absence of the protein in mutant ob/ob mice and resistance to its effects in db/db mice lead to extreme obesity and type II diabetes mellitus. No mutation of the ob-gene encoding for leptin has been found in obese humans so far. ob mRNA in adipocytes and serum leptin levels are positively related to adipose tissue mass. Receptors for leptin have been found in the choroid plexus and hypothalamus. A feedback inhibition of leptin on hypothalamic neuropeptide Y (NY) production is postulated, as hypothalamic NY concentrations are increased in ob/ob mice and NY induces food intake, insulin secretion and autonomic nervous system activity. Insulin increases triglyceride stores in fat cells and could thereby stimulate leptin secretion. The ultimate intracellular pathway within the adipocyte that stimulates or shuts off ob mRNA expression and consequent leptin production and secretion remains to be elucidated. Whether leptin will ever come to play a role in the treatment of human obesity remains an unanswered question at the present time.

Adipocytes↗
PubMed1996

Specific stimulation of brain serotonin mediated neurotransmission by dexfenfluramine does not restore growth hormone responsiveness in obese women.

OBJECTIVE: Growth hormone release in response to all known stimuli of GH secretion is blunted in obese subjects. Several studies, using d,l-fenfluramine (d,l-FF) as a serotoninergic tool, suggest that brain serotonin plays a role in the pathogenesis of this phenomenon. However, the effect of d,l-FF appears to be dependent on the stimulus used to induce GH release. Furthermore, d,l-FF has catecholamingergic properties apart from its capacity to stimulate serotonin release and to block its re-uptake. In this study, we investigated whether subchronic treatment with the highly selective serotoninergic drug dexfenfluramine (d-FF) affects the GH response to galanin or GHRH in obese subjects. DESIGN: The study had a randomized, cross-over, placebo controlled design. d-FF was administered in a dose of 15 mg twice daily during 6 days. On days 5 and 6 of treatment (with either d-FF or placebo) an i.v. bolus injection of 100 micrograms hGHRH(1-44) or a continuous infusion of p-galanin (40 pmol/kg/min over 40 minutes) were administered in randomized order. All tests were performed in the follicular phase of two consecutive menstrual cycles. PATIENTS: Eight obese women (body mass index (BMI) 34.5 +/- 3.6 kg/m2); 7 normal weight (BMI 21.9 +/- 1.9 kg/m2) age-matched control women. All women had a regular menstrual cycle. None used oral contraceptive drugs. MEASUREMENTS: GH response to either stimulus was measured both during treatment with d-FF and during treatment with placebo. RESULTS: The GH response to galanin and the response to GHRH were significantly smaller in obese subjects. d-FF significantly reduced the galanin induced GH secretion in obese subjects, but not in normal weight controls. It did not significantly affect GH release in response to GHRH in either group. CONCLUSION: This study confirms that GH secretion in response to stimuli with varying mechanisms of action is blunted in obese subjects. A decrease of central serotonin mediated neurotransmission does not appear to play a role in the pathogenesis of this phenomenon.

Adult↗
PubMed1996

Bodyweight change as an adverse effect of drug treatment. Mechanisms and management.

A number of drugs are capable of changing bodyweight as an adverse effect of their therapeutic action. Bodyweight gain is more of a problem than bodyweight loss. As bodyweight gain during drug treatment for any kind of disease may be the reflection of improvement of the disease itself, we will try to separate these effects from those due to drug-induced alterations of the mechanisms regulating bodyweight. Bodyweight gain may jeopardise patient compliance to the prescribed regimen and it may pose health risks. The body mass index (BMI) is determined by dividing bodyweight in kilograms by height in metres squared. A BMI of > or = 27 kg/m2 warrants therapeutic action; nutritional counselling and programmed physical exercise can be used as a basis. In general, if basic therapeutic measures are unsuccessful at controlling bodyweight gain then a change of drug might help. Finally, an anoretic drug may serve to support dietary measures. However, safety and efficacy has been demonstrated for only a few anorectic drugs when used as an adjunct to caloric restriction in the treatment of drug-induced obesity. Bodyweight is determined by complex mechanisms regulating energy balance. A number of neurotransmitter systems acting in several hypothalamic nuclei are pivotal to the regulation of body fat stores. Most drugs that are capable of changing bodyweight interfere with these neurotransmitter systems. The increment is dependent on the type and dose of the drug concerned. Some antidepressant drugs induce bodyweight gain, which may amount to 20 kg over several months of treatment. Monoamine oxidase inhibitors appear to cause less bodyweight change than tricyclic antidepressants. Selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitors cause bodyweight loss instead of bodyweight gain. Lithium may cause large increases in bodyweight. Generally speaking, the bodyweight change induced by antipsychotics is more often of clinical significance than the bodyweight change associated with the use of antidepressants. Again, the changes of bodyweight are dependent upon the type and dose of the antipsychotic drug involved. Although almost all antipsychotics induce bodyweight gain, molindone and loxapine appear to induce bodyweight loss. Anticonvulsants, especially valproic acid (sodium valproate) and carbamazepine, induce bodyweight gain in a considerable percentage of patients. Treatment with corticosteroids is associated with dose-dependent bodyweight gain in many patients. Corticosteroid-induced obesity aggravates other corticosteroid-associated health risks. Insulin therapy in diabetic patients usually increases bodyweight. Finally, sulphonurea derivatives, antineoplastic agents used for the treatment of breast cancer and several drugs used in migraine prophylaxis may cause bodyweight gain as well.

Antineoplastic Agents↗
PubMed1996

Serotoninergic drug-induced weight loss in carbohydrate craving obese patients.

RATIONALE: Serotoninergic neurotransmission, mainly in specific hypothalamic nuclei, plays an important role in the regulation of appetite. Dysfunction of this system has been postulated to result in the clinical picture of carbohydrate craving obesity. This subgroup of obese patients is characterized by a specific preference for high-carbohydrate and low-protein snacks. Centrally acting serotoninergic drugs, such as the serotonin re-uptake inhibitor d-fenfluramine, have been hypothesized to restore serotonin mediated control of food intake. OBJECTIVE: To test the hypothesis that serotoninergic drugs would induce a greater weight loss in carbohydrate craving (CC) than in non-carbohydrate craving (NC) obese patients. DESIGN: A three months open intervention study with d-fenfluramine 15 mg twice daily. In order to be able to study the effect of the drug alone, no dietary restrictions were imposed. Both the medical doctor and the patient were unaware of who was a carbohydrate craving obese patient and who was not. SUBJECTS: 10 CC and 10 NC patients, matched for sex, age, body mass index and family history of obesity. MEASUREMENTS: Height, body weight, food intake (energy intake and macronutrient selection) and patient compliance. RESULTS: CC patients lost 4.8 +/- 3.9 kg body weight or 15.9 +/- 13.5% of their pretreatment overweight, whereas NC patients lost 4.5 +/- 2.9 kg or 16.4 +/- 11.6% of their overweight (t-test for paired samples, P = 0.82 and P = 0.93 respectively). CONCLUSION: We conclude that CC patients do not constitute a subgroup of obese patients that should be treated with a serotoninergic drug preferentially.

Appetite Depressants↗
PubMed1995

Plasma amino acid ratios related to brain serotonin synthesis in response to food intake in bulimia nervosa.

Fifteen bulimic women (BN) and 19 healthy female controls (CO) were studied. The subjects were cross-over treated with either fluoxetine (FXT) or placebo during 4 days. They received, in randomized order, a breakfast containing pure carbohydrate (CHO) or a protein-rich (PROT) breakfast following day 3 and 4 of each treatment period. Twenty-nine different food items were offered for lunch. The fasting serum glucose and insulin concentrations and the fasting plasma tryptophan (Trp)/large neutral amino acid (LNAA) ratio were slightly higher in BN. The changes of these metabolic parameters in response to a CHO or PROT breakfast were similar in both groups. Across breakfast type, the plasma (Trp)/(LNAA) ratio at 120 min after breakfast was higher in BN. Total caloric intake at lunchtime was less in BN. In CO, less carbohydrate was selected at lunchtime following the CHO breakfast, an effect that was abolished by FXT. Breakfast type or FXT did not have any apparent effect on food intake at lunchtime in BN. This might indicate that bulimic subjects are less sensitive to serotoninergic stimuli than control subjects.

Adult↗
PubMed1995

Stress, serotonergic function, and mood in users of oral contraceptives.

The relationship between stress and changes in insulin levels, plasma ratio of tryptophan to other large neutral amino acids (LNAAs), mood, and food intake was investigated in women taking monophasic oral contraceptives containing progestagens. Subjects experiencing high levels of stress displayed significant decreases of insulin and tryptophan to other LNAAs ratios, before and after the consumption of a standard meal during the pill-free period as compared with the period of pill use. The decline of the tryptophan to other LNAAs ratio was accompanied by worsening of mood. In a control group of subjects experiencing low levels of stress there was no relationship between insulin and tryptophan to other LNAAs ratio, nor between tryptophan to other LNAAs ratio and mood. These results suggest that the combination of stress and alterations in sex hormones may be responsible for mood changes during the pill-free period in women taking oral contraceptives.

Adult↗
PubMed1995

Circadian distribution of motor activity and immobility in narcolepsy: assessment with continuous motor activity monitoring.

The circadian distribution of motor activity and immobility of 14 unmedicated narcoleptics and matched controls was evaluated by monitoring continuous wrist motor activity 5 successive days and nights at home. Sleep was also assessed by sleep logs. The amplitude of the circadian rhythm of motor activity and immobility was significantly lower in narcoleptics than in controls. The variables that best distinguish narcoleptics from controls were the diurnal and nocturnal mean duration of uninterrupted immobility, which can be explained by excessive daytime sleepiness and frequent nocturnal awakenings, respectively. Thus, measures of diurnal and nocturnal motor activity and immobility appear useful for the objective assessment of some of the sleep-wakefulness manifestations of narcolepsy.

Adolescent↗
PubMed1994

Insulin-induced decline of plasma amino acid concentrations in obese subjects with and without non-insulin-dependent diabetes.

Obesity-associated hyperaminoacidemia is traditionally interpreted as a consequence of insulin resistance. We performed two different experiments to investigate the effects of both obesity-associated insulin resistance and the insulin resistance of non-insulin-dependent diabetes mellitus (NIDDM) on amino acid metabolism. In the first experiment, we measured postabsorptive amino acid concentrations and their decline in response to an oral carbohydrate load in 19 obese nondiabetic women and 19 normal-weight nondiabetic controls. Obese subjects were more resistant to insulin with respect to its effects on glucose metabolism than normal-weight controls, as calculated by the method described by Matthews. However, postabsorptive plasma concentrations of the so-called large neutral amino acids (LNAA), namely phenylalanine, tyrosine, valine, leucine, and isoleucine, and their decrease in response to carbohydrate consumption were similar in both groups. In the second experiment, we compared the decrease of plasma concentrations of LNAA during a euglycemic, hyperinsulinemic clamp in obese subjects with and without NIDDM. Peripheral glucose uptake (PGU) was more impaired in NIDDM subjects compared with obese controls. Furthermore, hepatic glucose production (HGP) was less attenuated by insulin infusion in NIDDM than in control subjects. Postabsorptive plasma LNAA concentrations were not different in the two groups. Values obtained in either group were not different from the postabsorptive concentrations in the normal-weight control subjects of experiment 1. All amino acid levels decreased substantially in response to insulin infusion. The magnitude of the decrease was not significantly different in the two groups, except for a slightly greater decrease of the plasma isoleucine concentration in obese control subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

The influence of serotonergic neurotransmission on pituitary hormone release in obese and non-obese females.

It has been suggested that a defect in hypothalamic serotonergic neurotransmission may be partly responsible for the impaired pituitary hormone release in obese subjects. In this study we investigated basal serum pituitary hormone concentrations and pituitary hormone release in response to the sequential injection of four hypothalamic releasing hormones before and after a seven-day course of fluoxetine, which inhibits serotonin re-uptake by presynaptic neurons and acts specifically in the brain. Ten obese women (body mass index (BMI) 35.6 +/- 1.0 kg/m2) and nine women of normal weight (BMI 22.9 +/- 0.9 kg/m2) were studied in the early and mid-follicular phases of the menstrual cycle. Basal concentrations of pituitary hormones were measured at 09.00. Subsequently 200 micrograms of TRH and 100 micrograms of CRH, GnRH and GHRH were injected intravenously. The pituitary hormone response was measured at regular intervals until 180 min after the four injections. The experiment was repeated after a seven-day course of 60 mg fluoxetine orally. We found the basal concentrations of prolactin (PRL) and growth hormone to be significantly lower in obese subjects than in the normal controls. Basal concentrations of ACTH, beta-endorphin, TSH, LH and FSH in the two groups were comparable. Releasing hormone-induced responses in the two groups were not significantly different. Administration of fluoxetine "restored" the basal PRL concentrations in obese subjects. It did not affect the other basal hormone concentrations. Furthermore, fluoxetine treatment reduced TRH-induced TSH release in both normal and obese subjects. It did not influence the other releasing hormone-induced responses.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗
PubMed1993

Evidence for brain serotonin-mediated control of carbohydrate consumption in normal weight and obese humans.

A plasma insulin and amino acid-mediated mechanism is thought to modulate brain serotonin concentration, thereby regulating carbohydrate consumption on a meal to meal basis. It has been suggested that obesity is associated with a defect in the appetite control system. Furthermore, post-absorptive plasma levels of several amino acids are increased in obese subjects, which is ascribed to obesity-associated insulin resistance and/or hyperinsulinemia. We studied breakfast-induced changes in plasma ratios of tryptophan to other large neutral amino acids and associated differences in macro-nutrient composition of lunch food in normal weight and obese human subjects. The study was randomized, double blind and cross-over with a 2 x 2 factorial design with drug/placebo and type of breakfast as factors. Nineteen healthy, non-obese (body mass index (BMI) 22.5 +/- 1.9 kg/m2, mean +/- s.d.) and 19 obese (BMI 34.7 +/- 6.2 kg/m2) female volunteers were treated with either 60 mg fluoxetine (FXT), a serotonin re-uptake blocker specifically acting in the brain, or placebo for four days with a wash-out period between treatments of four weeks. The subjects received either a carbohydrate (CHO) breakfast (80 g maltodextrin, 300 kcal) or a protein-rich (PROT) breakfast (60% milk protein and 40% CHO, 300 kcal) on two consecutive days (days 4 and 5 of each treatment period). Plasma glucose, insulin and amino acids were measured at several time points after breakfast. Three hours after breakfast, subjects were able to choose from 29 different food items. Total energy content and weight of lunch food and energy percentage of each macronutrient were calculated.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗