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Biomedical subjects

A E Meinders

Publications and source records attributed to A E Meinders.

At least 109 records · Page 6Linked to original sources
PubMed1996

Decrease in cellularity and expression of adhesion molecules by anti-tumor necrosis factor alpha monoclonal antibody treatment in patients with rheumatoid arthritis.

OBJECTIVE: The effect of chimeric anti-tumor necrosis factor alpha (TNF alpha) monoclonal antibody (MAb) therapy on synovial inflammation was studied in order to address the hypothesis that anti-TNF alpha therapy leads to down-regulation of adhesion molecules and a decrease in inflammatory cell influx in synovial tissue (ST). METHODS: The immunohistologic features of synovial biopsy specimens, both before and 4 weeks after anti-TNF alpha MAb (cA2) therapy, were studied in 14 patients with rheumatoid arthritis (RA). The patients either received a placebo (n = 2), or were given intravenous doses of cA2 at 10 mg/kg (n = 5) or 20 mg/kg (n = 7). RESULTS: A significant (P < 0.03) reduction in the mean scores for T cells and for the adhesion molecules, vascular cell adhesion molecule 1 and E-selectin, was observed after therapy with 10 mg/kg or 20 mg/kg of cA2 in RA patients. CONCLUSION: The reduced expression of adhesion molecules, and the decrease in cellularity of rheumatoid ST after cA2 administration support the hypothesis that the antiinflammatory effect of anti-TNF alpha therapy might be partly explained by down-regulation of cytokine-inducible vascular adhesion molecules in ST, with a consequent reduction of cell traffic into joints.

Antibodies, Monoclonal↗
PubMed1996

Expression of the activation antigen CD27 in rheumatoid arthritis.

Differentiation of CD4+ T-cells is reflected by the change from the CD45RA+CD27+ phenotype via CD45RO+CD27+ to the CD45RO+CD27- phenotype. To provide insight into the migration and activation of T-cells at the site of inflammation in rheumatoid arthritis (RA), CD27 expression by T-cells in peripheral blood (PB), synovial fluid (SF), and synovial tissue (ST) as well as the levels of the soluble form of CD27 (sCD27) in plasma and SF were studied in patients with RA. Since CD4+CD27+ T-cells are involved in providing helper activity for B-cells, we also investigated the levels of rheumatoid factors in serum and SF in relation to CD27 expression. The mean level of sCD27, which is produced by CD27+ cells, and the mean percentage of CD27 T-cells within the CD4+CD45RA- subset were higher in SF than in PB. SF sCD27 levels were higher in the patients with RA than in the patients with osteoarthritis, who served as controls. In ST infiltration by CD4+CD45RO+CD27+ T-cells, could be demonstrated in the rheumatoid perivascular lymphocytic aggregates with a relative increase in the percentage of CD27- T-cells in the diffuse lymphocytic infiltrate. The sCD27 levels and the percentages of CD4+CD27+ cells in SF correlated positively with the levels of rheumatoid factors in serum and SF. The findings presented in this study suggest a continuous influx of preactivated CD4+CD45RO+CD27+ cells from the PB into the rheumatoid ST and further activation and differentiation to CD4+CD45RO+CD27- cells in situ, followed by migration to the SF. These activated T-cells are likely to play a role in synovial inflammation.

Adult↗
PubMed1996

Cerebral vasoconstriction in comatose patients resuscitated from a cardiac arrest?

OBJECTIVE: To determine the role of cerebral vasoconstriction in the delayed hypoperfusion phase in comatose patients after cardiac arrest. DESIGN: Prospective study. SETTING: Medical intensive care unit in a university hospital. PATIENTS: 10 comatose patients (Glasgow Coma Score +/- 6)successfully resuscitated from a cardiac arrest occurring outside the hospital. MEASUREMENTS: We measured the pulsatility index (PI) and mean blood flow velocity (MFV) of the middle cerebral artery, the cerebral oxygen extraction ratio and jugular bulb levels of endothelin, nitrate, and cGMP during the first 24 h after cardiac arrest. RESULTS: The PI decreased significantly from 1.86 +/- 1.02 to 1.05 +/- 0.22 (p = 0.03). The MFV increased significantly from 29 +/- 10 to 62 +/- 25 cm/s (p = 0.003). Cerebral oxygen extraction ratio decreased also from 0.39 +/- 0.13 to 0.24 +/- 0.11 (p = 0.015). Endothelin levels were high but did not change during the study period. Nitrate levels varied widely and showed a slight but significant decrease from 37.1 mumol/l (median; 25th-75th percentiles: 26.8-61.6) to 31.3 mumol/l (22.1-39.6) (p = 0.04). Cyclic guanosine monophosphate levels increased significantly from 2.95 mumol/l (median; 25th-75th percentiles: 2.48-5.43) to 7.5 mumol/l (6.20-14.0) (p = 0.02). CONCLUSIONS: We found evidence of increased cerebrovascular resistance during the first 24 h after cardiac arrest with persistent high endothelin levels, gradually decreasing nitrate levels, and gradually increasing cGMP levels, This suggests that active cerebral vasoconstriction due to an imbalance between local vasodilators and vasoconstrictors plays a role in the delayed hypoperfusion phase.

Adult↗
PubMed1996

Pulmonary oedema, pneumonia and mortality in submersion victims; a retrospective study in 125 patients.

OBJECTIVE: The identification of risk factors contributing to the development of pulmonary oedema, pneumonia and late mortality in submersion victims. DESIGN: A retrospective study of 125 submersion victims. SETTING: The medical intensive care unit in a university hospital. METHODS: Baseline examination on admission consisted of history, physical examination, arterial blood gas analysis and a chest radiograph. Patients were then classified into four groups: class I, baseline examination negative; class II, baseline examination positive, but mechanical ventilation not needed on admission; class III, mechanical ventilation required on admission; class IV, patients suffering from cardiopulmonary arrest. All patients who were not successfully resuscitated or who had expired within 24 h after admission were excluded for determination of the risk of pulmonary oedema and pneumonia. RESULTS: Class I patients did not develop pulmonary complications; neither pulmonary oedema nor pneumonia occurred in this group. In the remaining classes the incidence of pulmonary oedema was 72% and that of pneumonia, 14.7%. Stepwise logistic regression showed that pulmonary oedema was related to the type of water (seawater, ditch water, swimming pool) victims were submerged in and to the neurological state both at the time of rescue and on admission. The development of pneumonia was related to the use of mechanical ventilation (the risk was 52%). Pneumonia was not related to neurological state at the time of rescue or on admission, to body temperature on admission, to the prophylactic administration of antibiotics or to the use of corticosteroids. Mortality was high in class IV patients, but low in all other patients. Early mortality was 18.4% while late mortality was 5.6%. CONCLUSIONS: There is no need to hospitalise submersion victims when there are no signs or symptoms of aspiration upon arrival in the emergency room. All other patients should be admitted to an intensive care unit. The risk of pneumonia is high when mechanical ventilation is necessary. Mortality is high in patients with circulatory arrest on admission, but low in all other patients.

Adult↗
PubMed1996

Recurrent hypoglycaemia caused by the insulin autoimmune syndrome: the first Dutch case.

The insulin autoimmune syndrome is extremely rare outside of Japan. We describe a 45-year-old Caucasian woman who presented with fasting hypoglycaemia and weight gain. The presence of fasting insulin concentrations in excess of 1000 mU/l, very low C-peptide concentrations during hypoglycaemic attacks and high titres of insulin autoantibodies led to the diagnosis. Treatments aimed at decreasing endogenous insulin secretion by either dietary intervention alone or in combination with acarbose, octreotide or diazoxide had only limited success, while a 2-week course of immunosuppression with prednisone was without any antihypoglycaemic effect.

Autoantibodies↗
PubMed1996

Monitoring heparin treatment with the APTT: the effect of methodological changes on the APTT.

OBJECTIVE: To assess the effect on the desired activated partial thromboplastin time (APTT) of altered practice in the laboratory control of heparin treatment. METHODS: Descriptive study of the number of APTTs in the desired range (DR) in 1987 (historical controls) and in 1992/1993. In the latter period, four changes in the implementation of heparin treatment took place: another coagulation analyser was used, laboratory control was intensified with a nomogram as guideline, and the DR was changed form 90-120 to 45-60 s. Furthermore, a standard heparin solution of 417 U/ml was supplied by the hospital pharmacy. RESULTS: The total amount of APTTs in the desired range increased from 19% in 1987 to 46% in 1992/1993, and the DR was reached in 1987 in 1 day by 14%, and in 1992/1993 by 48% of patients. The mean daily heparin dose was higher in 1992/1993 (34.1 * 1000 U, 95% CI 33.4-34.8) than in 1987 (32.3 * 1000 U, 95% CI 31.5-33.0). The starting dose of heparin of 400 U/kg during the first day, following an initial bolus injection of 70 U/kg, was correct in 44% of patients, too low in 46%, and too high in 10%. CONCLUSIONS: The new policy in the laboratory control of heparin treatment resulted in an increased number of APTTs in the DR, and a shorter time to reach this.

Adolescent↗
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

Coeliac disease clinically manifest after vagotomy and oesophagectomy.

The clinical onset of coeliac disease may be precipitated by upper digestive tract surgery. A 66-year-old woman with asymptomatic coeliac disease that became clinically evident after oesophagectomy and vagotomy is presented. The surgery was performed for a squamous carcinoma of the hypopharynx. There had been no signs or symptoms of coeliac disease preoperatively. Persistent untreatable hypocalcaemia after the operation suggested the diagnosis. The role of surgery in unmasking asymptomatic coeliac disease is discussed.

Aged↗
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

The outcome of prolonged mechanical ventilation in elderly patients: are the efforts worthwhile?

We studied the outcome of prolonged (> 3 days) mechanical ventilation in 181 patients aged 70 and over and determined the risk factors for in-hospital mortality. The overall in-hospital mortality for the entire study group was 57.5%. The previous medical history did not influence the final outcome. Shock during the intensive care unit (ICU) stay and an admission diagnosis of cardiac arrest were independently correlated with in-hospital mortality. We conclude that the prognosis for patients aged 70 and over who need prolonged mechanical ventilation is mainly dependent on the acute health status and the occurrence of complications during the ICU admission.

APACHE↗
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↗