Mucopolysaccharidosis: secondarily induced abnormal distribution of lysosomal isoenzymes.

Total activities of acid hydrolases in liver of two patients with mucopolysaccharidosis are decreased for beta-galactosidase, alpha-galactosidase, and arylsulfatase A; total activities of four other hydrolases are normal or increased. The isoenzyme distribution of five hydrolases (beta-glucuronidase, alpha-glucosidase, beta- galactosidase, N-acetyl-beta-glucosaminidase, and alpha-galactosidase) is ábnormal in that the isoelectric points (by isoelectric focusing) of these enzymes are more acid than in control liver. Along with the isoenzyme abnormalities different kinds of glycolipids were stored in kidney, liver, and brain. The isoenzyme abnormalities can be reproduced in vitro by addition of chondroitin sulfate to a homogenate of normal liver, suggesting that stable binding occurs between mucopolysaccharides and the hydrolase molecules. After the addition of chondroitin sulfate, the total activity of beta-galactosidase is inhibited, whereas other hydrolases are affected only slightly or not at all.

[Effects of a structured medication review by geriatrician and clinical pharmacologist on appropriateness of pharmacotherapy in frail elderly inpatients]. / Interventies na een gestructureerde medicatie-analyse door klinisch geriater en ziekenhuisapotheker bij klinisch opgenomen kwetsbare oudere patiënten.

OBJECTIVE: To study the results of a structured medication review of geriatric inpatients by both geriatrician and hospital pharmacist/clinical pharmacologist. METHODS: Patients who were present at the geriatric ward were eligible for a review of their medication and medical problems using a screening form. Recommendations and questions following these forms were subsequently discussed in the gerontopharmacologic meeting ('GFO') held every two weeks. RESULTS: In a 30 month-period 44 GFO's were held during which 184 patients were discussed. A total of 206 recommendations were made and 115 questions were asked. Of the recommended interventions,134 (65%) were accepted by the geriatrician. To stop a medication (64/206), to change the dosage of a medication (60/206) and to switch to another medication (44/206) were the types of interventions most accounted for. CONCLUSION: Structured medication review led to a substantial number of medication changes in geriatric inpatients. Nearly two-thirds of the recommended interventions were accepted by the geriatricians. Seventy-two recommendations (35%) were not implemented due to logistic or patient-related reasons.

Interventies na een gestructureerde medicatie-analyse door klinisch geriater en ziekenhuisapotheker bij klinisch opgenomen kwetsbare oudere patiënten.

EFFECTS OF A STRUCTURED MEDICATION REVIEW BY GERIATRICIAN AND CLINICAL PHARMACOLOGIST ON APPROPRIATENESS OF PHARMACOTHERAPY OF FRAIL ELDERLY INPATIENTS: Objective To study the results of a structured medication review of geriatric inpatients by both geriatrician and hospital pharmacist/clinical pharmacologist. Methods Patients who were present at the geriatric ward were eligible for a review of their medication and medical problems using a screening form. Recommendations and questions following these forms were subsequently discussed in the gerontopharmacologic meeting ('GFO') held every two weeks. Results In a 30 month-period 44 GFO's were held during which 184 patients were discussed. A total of 206 recommendations were made and 115 questions were asked. Of the recommended interventions,134 (65%) were accepted by the geriatrician. To stop a medication (64/206), to change the dosage of a medication (60/206) and to switch to another medication (44/206) were the types of interventions most accounted for. Conclusion Structured medication review led to a substantial number of medication changes in geriatric inpatients. Nearly two-thirds of the recommended interventions were accepted by the geriatricians. Seventy-two recommendations (35%) were not implemented due to logistic or patient-related reasons.

[Thyrotoxicosis following the use of ashwagandha]. / Thyreotoxicose na gebruik van Ashwagandha.

A 32-year-old healthy woman developed thyrotoxicosis while taking capsules that contained ashwagandha herbal extract for symptoms of chronic fatigue. She was not taking any other remedies or medications. During the first few weeks, she took the capsules only occasionally without any symptoms, but after increasing the dose, she experienced clinical symptoms indicative of thyrotoxicosis. This was confirmed by laboratory assessment. The symptoms resolved spontaneously after discontinuation of the ashwagandha capsules and laboratory values normalised. To our knowledge, this relationship has not been reported previously in humans. Data from animal studies, however, have suggested that ashwagandha can increase serum concentrations of thyroid hormones. This case study suggests that thyrotoxicosis is a potentially serious side effect of ashwagandha.

[Drug rash with eosinophilia and systemic symptoms (DRESS) attributed to the oral skin-care supplement Imedeen]. / Geneesmiddelexantheem met eosinofilie en systemische symptomen (DRESS) in verband gebracht met het orale huidverzorgingssupplement Imedeen.

In a 56-year-old woman, 'drug rash with eosinophilia and systemic symptoms' (DRESS) was diagnosed. She had been admitted to hospital twice in two months because of fever and skin rash. Further studies revealed that in addition to the skin rash, the woman also suffered from eosinophilia, lymphadenopathy and a temporary liver-function disorder. After infectious and malignant causes had been excluded, the DRESS syndrome was diagnosed. The syndrome was attributed to the oral skin-care supplement Imedeen. She had stopped using this preparation previously, after which the symptoms decreased markedly. Now she was treated with corticosteroids and methotrexate and recovered completely after almost four months. The DRESS syndrome is characterised by skin rash, fever, lymphadenopathy and haematological abnormalities, especially eosinophilia and/or atypical lymphocytosis. Single or multiple organ involvement, especially of the liver, kidney, lungs and/or heart, is also common. The syndrome is associated with a number of different drugs.

[Ephedrine and ephedra in weight loss products and other preparations]. / Efedrine en Ephedra in afslankmiddelen en andere producten.

Ephedrine is a sympathicomimetic agent that stimulates the central nervous and cardiovascular systems and causes bronchodilatation. It is one of the alkaloids in the herb Ephedra which is the basis of several over-the-counter herbal products, among which a number of popular weight-loss products. The Dutch Inspectorate for Health Care has received reports of adverse reactions presumably associated with Ephedra-containing weight-loss products. These adverse reactions comprised mainly palpitations, stress, headache and insomnia. The Ministry of Health in Canada has recently requested a market recall of some ephedrine-containing herbal products in response to a large number of adverse reactions reported in association with these products. The adverse reactions included stroke, heart attacks, cardiac arrhythmias, seizures and psychotic disorders. The voluntary recall concerns especially products that were marketed without approval and contain Ephedra in combination with caffeine or other stimulants. In the Netherlands, the status of Ephedra-containing products is currently reconsidered.

[Hyponatraemia during the use of selective serotonin re-uptake inhibitors (SSRIs): reports from 1992-2002]. / Hyponatriëmie bij gebruik van selectieve serotonineheropnameremmers: meldingen in 1992-2002.

OBJECTIVE: To describe the reports of serotonin re-uptake inhibitor (SSRI)-induced hyponatraemia that were sent to The Netherlands Pharmacovigilance Centre Lareb and the Inspectorate for Health Care. DESIGN: Descriptive study. METHOD: Reports of SSRI-induced hyponatraemia received by Lareb and the Inspectorate for Health Care during the period 1 January 1992 to 1 July 2002 were described on the basis of symptoms, co-medication and comorbidity. RESULTS; A total of 42 cases were reported, 38 (90%) of which concerned women and 21 (50%) of which concerned the concomitant use of SSRIs and diuretics. The mean age was 74 years (range: 30-91). The mean serum sodium concentration was 115 mmol/l (range: 97-132). The most important symptoms were reduced consciousness, confusion, falls, nausea and vomiting. 3 patients (7%) died in the period of the reported adverse drug reaction and 27 patients (64%) were hospitalised, of which 4 (10%) to the intensive care unit. CONCLUSION: These reports of suspected SSRI-induced hyponatraemia were attended with significant morbidity and substantial mortality. The considerable morbidity and substantial mortality in combination with the increasing use of SSRIs necessitates a clarification of the actual incidence and severity of SSRI-induced hyponatraemia.

Compliance of energy-dense, small volume oral nutritional supplements in the daily clinical practice on a geriatric ward--an observational study.

INTRODUCTION: Compliance is important in optimizing the clinical effectiveness of oral nutritional supplements (ONS). Small volume, energy-dense ONS (ED-ONS; ≥ 2 kcal/ml) have been shown to improve compliance in clinical trial settings. However, data from clinical practice is still lacking. The aim of the present study was to evaluate the effect of ED-ONS on the compliance in an observational set-up to obtain data from daily clinical practice on a geriatric ward. METHODS: Geriatric inpatients, undernourished or at risk of undernutrition received two servings of either ED-ONS (125 ml, 2.4 kcal/ml: Nutridrink Compact Energy, Nutricia) or a standard ONS (S-ONS; 200 ml, 1.5 kcal/ml: Nutridrink) as part of their daily routine care. Patients were allocated to a group according to availability of beds and placement on the ward. Compliance (kcal/day and % of prescribed volume) was assessed by weighing returned bottles. Data were analyzed via Mixed Model for Repeated Measures. RESULTS: Forty-seven patients received ED-ONS, and 61 patients received S-ONS. Compliance was significantly higher with ED-ONS in geriatric inpatients compared to S-ONS ( 378 ± 14.0 kcal/day vs. 337 ± 13.6 kcal/day (mean ± SEM), p = 0.039, 63.0 ± 2.34% vs. 56.2 ± 2.26%, p = 0.039). Moreover, a trend (p=0.078) was observed towards an increasing difference in compliance over time. CONCLUSION: This study shows that compliance to ED-ONS is significantly better than to S-ONS in daily clinical practice. Although small, the difference in compliance seems to increase over time, suggesting clinical relevance with longer treatment.

Nutritional status of community-dwelling elderly with newly diagnosed Alzheimer's disease: prevalence of malnutrition and the relation of various factors to nutritional status.

OBJECTIVES: To determine the prevalence of malnutrition and its relation to various factors in community-dwelling elderly with newly diagnosed Alzheimer's disease (AD). DESIGN: Retrospective cross-sectional study. SETTING: Memory clinic in a rural part of the Netherlands. PARTICIPANTS: 312 Community-dwelling AD patients, aged 65 years or older, were included. MEASUREMENTS: At the time the diagnosis AD was made, socio-demographic characteristics and data on nutritional status (Mini Nutritional Assessment (MNA)), cognitive function (Mini Mental State Examination (MMSE), Cambridge Cognitive Examination (Camcog)), functional status (Interview for Deterioration in Daily Living Activities in Dementia (IDDD), Barthel Index (BI)) and behaviour (Revised Memory and Behaviour Problems Checklist (RMBPC)) were assessed. Characteristics of well-nourished patients (MNA score >23.5) were compared to characteristics of patients at risk of malnutrition (MNA score 17-23.5). Linear regression analysis was performed to assess the effect of various factors on nutritional status. RESULTS: The prevalence of malnutrition was 0% and 14.1% was at risk of malnutrition. AD patients at risk of malnutrition were more impaired in basic and complex daily functioning than well-nourished AD patients (median IDDD score 41.5 [25th -75th percentile 38.8-48.0] versus median IDDD score 40.0 [25th -75th percentile 37.0-43.0], p = 0.028). The degree of impairment in basic and complex daily functioning (IDDD) was independently related to nutritional status (MNA) (p = 0.001, B = -0.062). CONCLUSION: One in seven community-dwelling elderly with newly diagnosed AD is at risk of malnutrition. The degree of impairment in daily functioning is independently related to nutritional status. Therefore, assessment of the nutritional status should be included in the comprehensive assessment of AD patients. The relation between daily functioning, nutritional status and AD warrants further investigation.

Infantile spinal muscular atrophy. Unusual fiber typing and distribution in a muscle biopsy.

A right gastrocnemius muscle biopsy of a 13-month-old floppy male infant, which appeared at a more advanced age to suffer from an infantile spinal muscular atrophy, showed unusual histochemical changes: the chequer-board distribution was replaced by three groups of muscle fibers with a same mean narrow diameter of 12.5 micrometer. The smallest groups could easily be recognized as type I and type IIB fibers, while the largest group, involving more than 75% of the whole biopsy, revealed an intermediate hybrid fiber population, which would be classified as type I, if based on their phosphorylase and myofibrillar ATPase activities alone. The pathogenesis of this unusual finding is discussed.

A progressive congenital myopathy. Initial involvement of the diaphragm with type I muscle fiber atrophy.

An uncommon case of initial respiratory distress during the first months of life as the result of bilateral diaphragmatic weakness is presented. The biopsy and necropsy findings show a progressive congenital myopathy with type I muscle fiber atrophy and predominant involvement of the respiratory muscles. The lesions, observed in the central nervous system are due to the severe hypoxia. The morphological findings are discussed in relation to the etiology and the clinical picture of the disease.