PubMed Health⌕ Search

Biomedical subjects

H F Busch

Publications and source records attributed to H F Busch.

At least 37 records · Page 2Linked to original sources
PubMed1994

Ca2+ homeostasis in Brody's disease. A study in skeletal muscle and cultured muscle cells and the effects of dantrolene an verapamil.

Brody's disease, i.e., sarcoplasmic reticulum (SR) Ca(2+)-dependent Mg(2+)-ATPase (Ca(2+)-ATPase) deficiency, is a rare inherited disorder of skeletal muscle function. Pseudo-myotonia is the most important clinical feature. SR Ca(2+)-ATPase and Ca2+ homeostasis are examined in m. quadriceps and/or cultured muscle cells of controls and 10 patients suffering from Brody's disease. In both m. quadriceps and cultured muscle cells of patients, the SR Ca(2+)-ATPase activity is decreased by approximately 50%. However, the concentration of SR Ca(2+)-ATPase and SERCA1 are normal. SERCA1 accounts for 83 and 100% of total SR Ca(2+)-ATPase in m. quadriceps and cultured muscle cells, respectively. This implies a reduction of the molecular activity of SERCA1 in Brody's disease. The cytosolic Ca2+ concentration ([Ca2+]i) at rest and the increase of [Ca2+]i after addition of acetylcholine are the same in cultured muscle cells of controls and patients. The half-life of the maximal response, however, is raised three times in the pathological muscle cells. Addition of dantrolene or verapamil after the maximal response accelerates the restoration of the [Ca2+]i in these muscle cells. The differences in Ca2+ handling disappear by administration of dantrolene or verapamil concomitantly with acetylcholine. The reduced Ca2+ re-uptake from the cytosol presumably due to structural modification(s) of SERCA1 may explain the pseudo-myotonia in Brody's disease. Single cell measurements suggest a beneficial effect of dantrolene or verapamil in treating patients suffering from Brody's disease.

Acetylcholine↗
PubMed1993

[Intravenously-administered immunoglobulins as first-choice agent in juvenile dermatomyositis].

Dermatomyositis is an acquired disease characterised by symmetric predominantly proximal muscle weakness of the arms and legs, and misery. It may be associated with myalgia and there is often a characteristic rash. The mainstay of therapy is corticosteroids. Recently efficacy of intravenous immunoglobulin (IVIg) in chronic refractory dermatomyositis was reported. Because corticosteroids can cause serious side effects, we treated a seven-year-old girl suffering from dermatomyositis with IVIg as initial therapy. After two courses of IVIg infusions at a dose of 0.4 g/kg/day for five consecutive days, the patient made a rapid and complete recovery. This case shows that IVIg may be effective as initial therapy in patients with dermatomyositis. Whether IVIg is really a better treatment than corticosteroids should be investigated in a randomised study.

Biopsy↗
PubMed1993

[Application of combined DNA and dystrophin protein analysis in the diagnosis of Duchenne's and Becker's muscular dystrophy in 102 Dutch patients].

The recent progress in molecular genetic studies on Duchenne and Becker muscular dystrophy (DMD, BMD) had an important spin-off for our diagnostic abilities of both muscle disease. The mapping and isolation of the DMD gene which codes for the 427 kD cytoskeletal protein dystrophin made it possible to diagnose 80-85% of the patients by means of DNA analysis. At present, most of the remaining 15-20% of the patients can be diagnosed by protein analysis. In this report we describe the analysis of dystrophin in a group of 102 Dutch patients with muscular dystrophies. An immunohistochemical and immunobiochemical study of dystrophin was performed on muscle tissue, partly integrated with DNA analysis. In this study we underline the value of dystrophin analysis in all patients suspected of DMD, BMD or other muscular dystrophies, particularly in those without detectable DNA mutations. By means of integrated DNA/dystrophin analysis 98% of the DMD patients and 90% of th BMD patients and their families can now be provided with an unambiguous diagnosis. In particular, discrimination between BMD and other muscular dystrophies has strongly improved.

Adult↗
PubMed1993

Problems with the biochemical diagnosis in mitochondrial (encephalo-)myopathies.

Patients suffering from a mitochondrial (encephalo-)myopathy have a remarkable clinical heterogeneity. A reliable and extensive investigation must be performed in order to obtain a correct diagnosis, but many factors may influence the ultimate results of these investigations leading, under certain circumstances, to an incorrect diagnosis. Patients selection is of crucial importance. Metabolic examination of body fluids, particularly with respect to lactate accumulation, is used as a selection criterion for further examinations. Numerous aspects associated with this metabolic examination have been critically evaluated, including the phenomenon of other causes of lactic acidaemia apart from mitochondrial disorders. Correct performance of in vivo function tests may contribute to a reduction of the number of missed diagnoses. Selection of the controls for biochemical investigations must be accurately be performed to obtain reliable reference values. Knowledge of the age-dependency of the biochemical parameters is necessary for a correct interpretation. It goes without saying that the choice of the tissue for biochemical investigations is of utmost importance. Knowledge of the tissue-specific occurrence of some defects in the mitochondrial respiratory chain is necessary. The biochemical examinations can be performed both in biopsy and autopsy material but only under certain conditions. Diagnostic approach requires application of reliable biochemical methods which are described. One of the most intriguing aspects in the diagnosis of mitochondrial disorders is the significance of a defect in relation to the residual enzyme activity found in the patient. Moreover, attention is paid to relevant items such as the occurrence of multiple and secondary defects.(ABSTRACT TRUNCATED AT 250 WORDS)

Acidosis, Lactic↗
PubMed1993

Intravenous immunoglobulin treatment in patients with chronic inflammatory demyelinating polyneuropathy: a double blind, placebo controlled study.

Patients with a clinical diagnosis of chronic inflammatory demyelinating polyneuropathy (CIDP) were randomised in a double-blind, placebo-controlled multicentre trial to investigate whether high-dose intravenous immunoglobulin treatment (IVIg) for 5 consecutive days has a beneficial effect. Fifteen patients were randomised to IVIg and 13 to placebo. In the IVIg treatment group 4 patients improved and 3 patients in the placebo group. The degree of improvement of the patients in the IVIg treatment group was no different from the patients in the placebo group. Electrophysiological studies did not show significant differences between the groups. Since a previously performed cross-over trial showed that a selected group of CIDP patients responded better to IVIg than to placebo, it is concluded that we need better criteria to select CIDP patients for treatment with IVIg.

Chronic Disease↗
PubMed1992

Birth and population prevalence of Duchenne muscular dystrophy in The Netherlands.

Mutations causing Duchenne muscular dystrophy (DMD) have a short survival. Therefore, birth and population prevalence are maintained by new mutations. The present inventory was made to estimate the birth and population prevalence rates of DMD in the Netherlands. Seven methods of case identification were used. Data on 496 definite, probable or possible DMD patients born since 1961, or alive on January 1, 1983, were obtained. Several methods gave an estimated ascertainment of more than 95%. The prevalence rate at birth of DMD was estimated at 23.7 x 10(-5) (1:4215) male live births (MLB) yearly. The prevalence rate in the male population on January 1, 1983 was 5.4 x 10(-5) (1:18496). About 1% of the males in this study may have autosomal recessive Duchenne-like muscular dystrophy. Until now there has been no convincing evidence for geographic differences in DMD prevalence at birth. A list of frequency studies of Duchenne muscular dystrophy is included. The DMD mutation rate calculated by the indirect method is 7.9 x 10(-5) genes per generation. However, this may well be an over-estimate, as this method does not account for germline mosaicism. Using a modified sex ratio method the proportion of sporadic DMD among all cases was estimated to be 0.106 (range 0-0.332). High frequency of germline mosaicism in DMD is a likely cause for the apparent lack of sporadic cases as found in previous studies, if mutation rates in male and female gametes are equal. Therefore, methods for estimating the proportion of new mutants in DMD should take germline mosaicism into account. The modified sex ratio method allows incorporation of data on germline mosaicism if available.

Cohort Studies↗
PubMed1991

Intravenous immunoglobulin treatment in patients with chronic inflammatory demyelinating polyneuropathy. Clinical and laboratory characteristics associated with improvement.

Of 52 patients fulfilling the criteria of chronic inflammatory demyelinating polyneuropathy, 20 (38%) did not improve after intravenous immunoglobulin treatment, two (4%) had a short-lasting improvement and subsequent infusions had no effect, nine (17%) reached a spontaneously or therapeutically induced complete remission, and 21 patients (40%) needed intermittent infusions to maintain improvement. All patients who improved initially had symptoms that significantly interfered with life-style. After treatment, 90% of these patients were independent in their daily activities. Significantly associated with improvement were disease duration of less than 1 year, progression of weakness until treatment, absence of discrepancy in weakness between arms and legs, areflexia of the arms, and slowed nerve conduction velocity of the motor median nerve. The probability of improvement if all these features are present in 93%.

Adolescent↗
PubMed1990

Oxidative phosphorylation in human muscle in patients with ocular myopathy and after general anaesthesia.

The fuel preference of human muscle mitochondria has been given. Substrates which are oxidized with low velocity cannot be used to detect defects in oxidative phosphorylation. After general anaesthesia, the oxygen uptake with the different substrates is much lower than after local analgesia. The latter was therefore used in the subsequent study. In 15 out of 18 patients with ocular myopathy, defects in oxidative phosphorylation could be detected in isolated muscle mitochondria prepared from freshly biopsied tissue. Measurement of the activity of segments of the respiratory chain in homogenate from frozen muscle showed no, or minor defects. In two of these patients showing exercise intolerance, decreased oxidation of NAD(+)-linked substrates and apparently normal mitochondrial DNA, further study revealed deficiency of pyruvate dehydrogenase in a girl with ptosis and a high Km of complex I for NADH in a man. Both patients responded to vitamin therapy.

Adolescent↗
PubMed1990

Non-familial degenerative disease and atrophy of brainstem and cerebellum. Clinical and CT data in 47 patients.

We studied the clinical features of 47 patients with a non-hereditary degenerative disease and with atrophy of brainstem or cerebellum or both in CT scanning. There was no relation between the CT findings and duration or severity of the disease, nor with the kind of the neurological signs which comprised ataxia, a hypokinetic rigid syndrome, oculomotor abnormalities, upper and lower motor neuron signs, orthostatic hypotension and dementia. The 2 main diagnoses were olivopontocerebellar atrophy (OPCA), or a combination of OPCA and striatonigral degeneration (SND). The differential diagnosis with Parkinson's disease and progressive supranuclear palsy was discussed. We concluded, that a CT scan is warranted in all cases of suspected Parkinson's disease, especially in those without tremor, and in cases of motoneuron disease with broad-based gait. In our patients with mainly hypokinesia and rigidity, levodopa treatment had no or brief beneficial effects. If ataxia predominated, OPCA appeared the most sensible diagnosis; if a hypokinetic-rigid syndrome predominated, the diagnoses SND plus OPCA appeared the most suitable. We assessed the degree of atrophy on CT subjectively, because an interobserver study of 60 normal CT scans, did not produce reliable measurements.

Adult↗
PubMed1990

Congenital demyelinating motor and sensory neuropathy with focally folded myelin sheaths.

Six patients (5 index cases and 1 sib) with a congenital motor and sensory neuropathy are described. The clinical, genetic and electrophysiological features resembled Dejerine-Sottas disease or hereditary motor and sensory neuropathy (HMSN) type III. Sural nerve biopsy of 5 patients revealed segmental demyelination and remyelination with hypertrophic changes, although onion bulbs were not as ubiquitous as in classical HMSN type III. A striking discriminating feature from HMSN type III was an abundance of focal myelin thickenings (tomacula) present in nearly all teased fibres. Possible pathogenic implications are discussed. These cases corroborate the heterogeneity of congenital motor and sensory neuropathies.

Adolescent↗
PubMed1989

Carnitine deficiency, mitochondrial dysfunction and the heart. Identical defect of oxidative phosphorylation in muscle mitochondria in cardiomyopathy due to carnitine loss and in Duchenne muscular dystrophy.

Cardiomyopathies are often caused by a metabolic defect. Carnitine deficiency and mitochondrial defects in the metabolism of acyl-CoA, including defects in oxidative phosphorylation, start the same circular mechanism of mitochondrial doom. Patients with cardiomyopathy due to carnitine loss are cured by carnitine supplementation. In such a patient we found defective oxidative phosphorylation in isolated muscle mitochondria. The stimulation of the respiratory rate with all substrates by ADP was decreased, probably the cause of inhibition of the adenine nucleotide translocator by accumulating long-chain acyl-CoA. The same condition was encountered in patients with Duchenne muscular dystrophy, who often get cardiomyopathy in the course of the disease process.

Acetyl Coenzyme A↗
PubMed1989

Anticipation in myotonic dystrophy: fact or fiction?

In 1918 Fleischer reported that after transmission from one generation to the next, myotonic dystrophy has an earlier onset and is more severe. The hypothesis put forward by Penrose in 1948 that 'anticipation' is caused by bias of index case selection was based on theoretical arguments only and has not been supported by clinical observations. This hypothesis was tested in a clinical and genetic study of 14 families with myotonic dystrophy. Excluding index patients, an earlier onset in the child was found in 98% of 61 parent-child pairs. A greater mean difference in age of onset was found with transmission via the father than via the mother. The comparison of the severity of the disease between parents and children was difficult because of the variation in symptoms but, in general, the disease was more severe in the child than in the parent. The penetrance of the abnormal gene was nearly complete in the 14 families combined, leaving little room for the observation of 'complementary' parent-child pairs in the future. Also in retrospect no complementary parent-child pairs were found in the first generations. Fertility was severely reduced only in the very early onset patient group and this selective infertility cannot be responsible for the total amount of anticipation observed. It is therefore concluded that anticipation may be inherent in the transmission of myotonic dystrophy. This has important consequences for genetic counselling.

Adult↗
PubMed1989

Chronic inflammatory demyelinating polyneuropathy. Conduction failure before and during immunoglobulin or plasma therapy.

An earlier study has shown that patients with chronic inflammatory demyelinating polyneuropathy may improve after the infusion of fresh frozen plasma or high dose intravenous immunoglobulin. We studied 8 such responding patients with neurophysiological techniques. Before treatment all patients had decreased compound muscle action potentials (CMAP) and slowing of conduction. During several courses of treatment a progressive increase of the CMAPs occurred and in 5 patients a correlation between the CMAPs of the abductor pollicis brevis muscle and grasp force could be demonstrated. In 2 patients, increase in strength was correlated with shortening of the distal motor latency; no significant relationships were found between strength and conduction velocity. Different patterns in the distribution of conduction failure were observed. In 2 patients, lesions were distributed along the length of the motor fibres, whereas the sensory system was spared. In another 2 patients the lesions, most likely demyelinating, were localized distally and included the sensory system. The 4 remaining patients were more difficult to classify, but individually showed greater resemblance to one or other of the two described patterns. Different patterns of conduction failure may reflect different pathogenetic mechanisms.

Action Potentials↗
PubMed1989

Congenital paucity of secondary synaptic clefts (CPSC) syndrome in 2 adult sibs.

We studied 2 elderly sibs with a congenital form of myasthenia who had ptosis since early childhood. The extraocular muscles were weak and the proximal limb muscles became slowly weaker throughout life. Laboratory investigations of biopsies of intercostal muscle from these patients showed the following abnormalities: the amplitude of miniature end-plate potentials was small and the binding of 125I-alpha-bungarotoxin at the end-plate area was reduced, suggesting a considerable reduction of acetylcholine receptors (AChRs). Secondary synaptic clefts were scarce, whereas the number of end-plates per muscle fiber was increased. There was no indication of impaired transmitter release as the quantal content was within the range of controls. We conclude that these patients suffered from the congenital paucity of secondary synaptic clefts (CPSC) syndrome, described recently in 2 cases of myasthenic children, and suggest that the CPSC syndrome is a developmental disorder in which a deficiency of AChRs may be caused by a decreased clustering or insertion of AChRs. The increased number of end-plates per muscle fiber in both patients could serve as a compensatory mechanism.

Bungarotoxins↗
PubMed1988

Prospect for enzyme therapy in glycogenosis II variants: a study on cultured muscle cells.

Impairment of skeletal muscle function is the common feature of distinct clinical forms of glycogenosis type II. In the present study, muscle cultures from different patients were used to investigate the cause of clinical heterogeneity and the feasibility of enzyme replacement therapy. The activity of acid alpha-glucosidase appears to be the primary factor in determining the extent of lysosomal glycogen storage in muscle, and thereby the clinical severity of the disease. Neutral alpha-glucosidases do not seem influential. Correction of the enzymatic defect was achieved in skeletal muscle cultures from patients by administration of a "high-uptake" form of acid alpha-glucosidase, purified from human urine. The enzyme reaches the lysosomes, including the glycogen storage vacuoles, and the lysosomal glycogen content is reduced to control level. In normal muscle cells 20% of the total cellular glycogen pool is segregated in lysosomal compartments. This percentage is higher than in fibroblasts, which may partly explain why muscles are more prone to store glycogen. The relevance of this study for enzyme therapy is discussed.

Cells, Cultured↗