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W Müller-Felber

Publications and source records attributed to W Müller-Felber.

At least 19 recordsLinked to original sources
PubMed1999

Markedly different course of Friedreich's ataxia in sib pairs with similar GAA repeat expansions in the frataxin gene.

Friedreich's ataxia (FA) is most frequently caused by intronic trinucleotide repeat expansions in the frataxin gene on chromosome 9. The broad clinical spectrum includes late-onset FA (LOFA) and FA with retained reflexes (FARR). The size of the GAA expansions accounts for most, but not all, of the clinical variability. We report the unusual occurrence of LOFA and FARR in two siblings of patients with classical early-onset FA in two families. In spite of the markedly different course of the disease, the respective siblings harboured GAA repeat expansions of similar size in leucocytes. Since haplotype-related variability is not likely among siblings, we suppose that this intrafamilial phenotype variability is due to somatic mosaicism, with the more severely affected siblings harbouring the larger expansions in spinal cord and other affected tissues. In view of these results, genetic counseling and predictions on the course of FA are particularly difficult, even if an expansion mutation is found.

Adult↗
PubMed1999

Localization of transforming growth factor beta in association with neuromuscular junctions in adult human muscle.

Transforming growth factors-beta 1, 2, and 3 are known for their regulatory function in embryogenesis, fibrogenesis, and tissue repair of different cell types. A trophic function of TGF-beta subclasses for motoneurons has been shown in vitro. TGF-beta 1 is a potent survival factor for cultured embryonic rat motoneurons. In addition, TGF-beta 1 stimulates proliferation of rat Schwann cells. Recently, TGF-beta 2 has been reported to be associated with the subsynaptic nuclei of mature rat neuromuscular junctions. In this study, we investigated the expression of TGF-beta 1, 2, and 3 at neuromuscular junctions in skeletal muscle of 11 adults without neuromuscular disease. On muscle biopsies, neuromuscular junctions were depicted by acetylcholine esterase reaction and acetylcholine receptor antibodies. TGF-beta 1; 2, and 3 were stained immunohistochemically with monoclonal antibodies. Some muscle fibers showed low levels of inhomogeneous immunoreactivity for both TGF-beta 1 and TGF-beta 3. Intense immunoreactivity of TGF-beta 1 and 3 was shown at the postsynaptic area of neuromuscular junctions. TGF-beta 2 was expressed in the same subcellular distribution, but less strongly. In conclusion, the colocalization of TGF-beta with neuromuscular junctions may suggest a significant function in neuromuscular communication.

Acetylcholinesterase↗
PubMed1998

Tenascin is a useful marker in the diagnosis of inflammatory myopathies.

The expression of tenascin, NCAM, vimentin and HSP-70 was examined in 15 patients with dermatomyositis and 12 patients with polymyositis. All biopsies with dermatomyositis showed a confluent network of tenascin expression in the extracellular space. This network surrounded numerous fibers (39 up to 320). Tenascin expression preceded other histological and immunohistochemical signs of dermatomyositis such as the expression of N-CAM and vimentin and the appearance of perifascicular atrophy and inflammatory response. Tenascin expression was found in 3 biopsies where microtubular inclusions in the arteriolar walls were absent. In contrast, tenascin expression was confined to the surroundings of necrotic fibers also expressing vimentin or N-CAM in polymyositis. In general, tenascin was found in the vicinity of inflammatory cells, only. These findings suggest that tenascin is induced by ischemic stress in dermatomyositis. Widespread tenascin expression in a fascicular distribution is a specific marker, if an inflammatory myopathy has been proven by standard techniques. In some cases, tenascin staining might confirm the clinical diagnosis of dermatomyositis, where other histological findings are inconclusive.

Adolescent↗
PubMed1998

Drug-induced systemic lupus erythematosus after 8 years of treatment with carbamazepine.

This is the report of a late-onset carbamazepine-induced systemic lupus erythematosus in a 34-year-old patient who had been treated with daily carbamazepine for 8 years because of complex partial seizures. When carbamazepine was discontinued, symptoms rapidly improved and antinuclear antibodies disappeared. So far, few cases have been reported of carbamazepine-induced lupus erythematosus within months after the start of treatment. This is the first case report about carbamazepine-induced systemic lupus erythematosus with serological confirmation after years of treatment without side effects.

Adult↗
PubMed1998

Changes of sonographic, magnetic resonance tomographic, electromyographic, and histopathologic findings within a 2-month period of examinations after experimental muscle denervation.

This study compares sonographical, histopathological, magnetic resonance imaging (MRI), and electromyographical (EMG) findings following acute muscle denervation. We performed an experimental denervation of the supraspinatus and infraspinatus muscles on 35 New Zealand white rabbits by segment resection of the suprascapular nerve. The sonographical appearance of the supraspinatus muscle was followed and documented at short time intervals within a 2-month follow-up period. The sonographical, histopathological, and MRI changes due to denervation suggest a regular pattern. Apart from the reduction of the muscle diameter, there were considerable sonographical signs of denervation with an increase of echointensity and inhomogenicity of echotexture that appeared on day 14 after injury, and progressed continuously with time. MRI revealed a remarkable increase in signal intensity 3 weeks after denervation and reproducible T2 times. Pathological spontaneous activity on EMG could also be detected from day 14 after injury. Conventional histopathological staining methods (H&E, NADH, ATPase, basic and acid phosphatase) confirmed denervation and absence of reinnervation. The first nonspecific histopathological changes were seen 11 days after denervation in the form of moderately atrophic fibers. Typical histopathological signs of denervation appeared 3 weeks after nerve dissection. In summary, EMG, ultrasound, MRI, and histopathology each showed first abnormalities after about 2 weeks. In addition to EMG, sonography and MRI can document the course of muscle atrophy and mesenchymal abnormalities in neurogenic muscle lesions.

Animals↗
PubMed1998

Marinesco Sjögren syndrome with rhabdomyolysis. A new subtype of the disease.

Four children from two families with characteristics of Marinesco-Sjögren syndrome (congenital cataract, ataxia) are presented. All children had clinical and neurophysiological signs of a demyelinating polyneuropathy. Three of them developed acute rhabdomyolysis with marked weakness and CK levels of up to 40,000 U/I following a viral infection. In all children CK levels returned to normal within two weeks. Symptoms were recurrent in one of the children and resulted in a severe disability. In two other children recovery of motor function took about a month following the first attack. Metabolic disorders of the muscle were excluded by pathobiochemical examination of a muscle biopsy in one of the children. In conclusion, acute rhabdomyolysis can occur as a neuromuscular complication of Marinesco-Sjögren syndrome.

Child↗
PubMed1997

Congenital myasthenic syndromes: clinical and genetic analysis of 18 patients.

Congenital myasthenic syndromes (CMS) are a group of rare gentic disorders in which neuromuscular transmission is compromised by a variety of mechanisms, other than autoimmunity. Recently, substantial progress has been made by the identification of mutations in acetylcholine receptor (AChR) genes which cause CMS. We report on the clinical and genetic analysis of 18 independent CMS patients. All patients were clinically classified as sporadic cases of CMS (group III according to ENMC consensus). In order to investigate the prevalence of AChR mutations in this group we analyzed structural domains of the AChR genes at strategically important sites - the channel pore-lining regions (M2 domains) of the alpha, beta and epsilon subunits, and the extracellular domain close the acetylcholine (ACh) binding site. All patients showed wild-type sequence in these regions, mutations were not detected. Therefore, we conclude, that point mutations in domains which are known to cause slow channel congenital myasthenic syndromes (SCCMS) are rare in group III-patients in Germany. Determining the genetic defects causing CMS may have implications for diagnosis and genetic counseling of CMS patients. Moreover, this may be important for the therapeutic management of CMS as some patients may profit form quinidine sulfate. Therefore, further efforts will be undertaken to elucidate the underlying defects of CMS.

Adolescent↗
PubMed1997

Delayed colonic transit times in amyotrophic lateral sclerosis assessed with radio-opaque markers.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder, characterized by progressive loss of motor neurons. However, ALS has been recognized to involve several non-motor systems, subclinically. Cardiac and sudomotor autonomic involvement in ALS has been described. Recently, delayed gastric emptying was reported. The aim of this study was to assess colonic transit time in patients with ALS. Therefore, measurement of total and segmental colonic transit times using radio-opaque markers was performed in 14 patients with ALS and 14 healthy age-matched volunteers. Multiple-ingestion, single-radiograph technique was used. Segmental and colonic transit times were calculated from the number of retained markers. Nine of 14 patients with ALS showed markedly delayed colonic transit times if compared to healthy controls. Colonic transit in ALS patients was significantly delayed in the right and left colon; the rectosigmoid transit did not show major delay. The colonic transit times did not correlate with bulbar involvement, Norris score, walking disability or duration of the disease. In summary, colonic dysfunction in ALS may be a result of inactivity or inadequate fiber intake. However, it also may represent a gastrointestinal autonomic involvement due to nerval degeneration. Considering ALS as a multisystem disorder including the autonomic nervous system may have implications for research into pathogenesis and therapy of neurodegenerative disease.

Abdominal Pain↗
PubMed1995

[Paresthesia].

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Afferent Pathways↗
PubMed1994

Myofibrillogenesis in primary tissue cultures of adult human skeletal muscle: expression of desmin, titin, and nebulin.

To investigate the in vitro development of myofibrils in skeletal muscle cells derived from adult human muscle biopsies, immunohistochemical analysis was performed using monoclonal antibodies against desmin, titin, and nebulin. Diffuse desmin reactivity was detected 48 h after plating in about 60% of all mononucleated cells. This supports the use of desmin as a marker for undifferentiated rhabdomyosarcomas in man. Titin was visible from day 4 onwards, while nebulin was not found in mononucleated cells. After 1 week polynucleated myotubes appeared, and grew up to 30 days. Desmin was distributed diffusely throughout the cytoplasm until day 21, when the pattern became patchy. Titin began to be organized in a predominantly longitudinal orientation at day 15, while nebulin, which appeared for the first time in fusing myoblasts on the fifth to the seventh day, was almost immediately organized in a dotted longitudinal pattern, which became a Z line connected striation in matured myotubes.

Cells, Cultured↗
PubMed1994

[Rhabdomyolysis in neuroleptic therapy: an abortive malignant neuroleptic syndrome?].

We report on the case of a 24 year old female patient, who, at first developed during 8 weeks of neuroleptic therapy parkinsonism and then, after improvement of psychopathology an acute rhabdomyolysis. Hyper-Ck-aemia up to 11,340 U/l was observed. Laboratory parameters normalized shortly after neuroleptics had been withdrawn and no further complications followed. Symptomatology is discussed with special reference to the possibility of an abortive malignant neuroleptic syndrome.

Adult↗
PubMed1993

The clinical spectrum of Friedreich's ataxia in German families showing linkage to the FRDA locus on chromosome 9.

The clinical features of Friedreich's ataxia are described and reevaluated in a group of 14 German patients from 9 independent families. In contrast to previous studies, demonstration of linkage to the Friedreich's ataxia locus (FRDA) on chromosome 9p allowed confirmation of the genetic homogeneity of the disease in the patients under study. Marked variability within families was observed for age of onset of the disease (4-24 years) and for age of becoming wheelchair bound (17-37 years). Electrocardiographic changes were present in all and echocardiographic changes in 50% of the patients. Pathological changes of visual evoked potentials were detected in only 50% of the patients while brainstem auditory evoked potentials and somatosensory evoked potentials were always abnormal.

Adolescent↗
PubMed1993

Heterozygotic gene expression in endomyocardial biopsies: a new diagnostic tool confirms the Duchenne carrier status.

Identification of the defective gene and the absent gene product dystrophin can substantiate the clinical evidence for manifesting X-linked Duchenne type muscular dystrophy (DMD). It is not always possible, however, to rule out definitely a clinically asymptomatic carrier status in question, since even in the proven carrier DNA analysis is often inconclusive, and multinucleated skeletal muscle fibers express a basically normal membrane dystrophin. To substantiate the value of endomyocardial biopsy as a new tool for detection of the DMD carrier status we examined an endomyocardial biopsy of a volunteer who met the clinical criteria of a DMD carrier. Dystrophin immunohistochemistry and western blot of her skeletal muscle biopsy were inconclusive, and polymerase chain reaction and cDNA analysis failed to locate directly the X-chromosomal defect. We observed a clearcut mosaic of dystrophin-positive and -negative mononucleated cardiac muscle cells, reflecting a heterozygote carrier status in her endomyocardial biopsy, whereas 20 controls were uniformely positive. The incidence of DMD (1:3000 males) and especially the 30% spontaneous mutation rate, still the major pitfall in DNA analysis, show the need for an additional diagnostic tool.

Adult↗
PubMed1993

High incidence of carpal tunnel syndrome in diabetic patients after combined pancreas and kidney transplantation.

Fifty-eight patients with long-standing type 1 (insulin-dependent) diabetes were studied prospectively after combined pancreas and kidney transplantation for a mean observation period of 47.9 months (range 17-116 months). Thirty-three per cent of these patients (19/58) developed carpal tunnel syndrome after a mean interval of 1.7 years (range 3 months-5 years). This rate is about twice that in type 1 diabetic patients. The manifestation of carpal tunnel syndrome was not significantly associated with worsening of diabetic polyneuropathy or with deterioration of kidney or pancreas function. In all but one patient symptoms improved without surgical intervention. This study suggests that patients after combined pancreas and kidney transplantation have an increased risk of carpal tunnel syndrome for which the etiology and pathophysiology are unknown. In most patients no surgical intervention is necessary.

Adult↗
PubMed1993

Cross-sectional study of peripheral microcirculation in diabetic patients with microangiopathy: influence of pancreatic and kidney transplantation.

Diabetic vascular lesions and peripheral autonomic neuropathy are both closely linked to long-term metabolic control of diabetes. Transcutaneous oxygen tension (PtcO2) measurements were made to elucidate whether autonomic neuropathy disturbs the cutaneous microcirculatory blood flow, and whether long-term glucose normalization ameliorates such impairment. Twenty-eight type 1 (insulin-dependent) diabetic patients in whom clinically significant macroangiopathy had been excluded by angiography were studied, subdivided into group A (n = 14; before simultaneous pancreas/kidney transplantation (SPKT); mean age 35 years, range 22-51 years; mean duration of diabetes 24 years, (range 15-32) years and group B (n = 14; mean 31 months, range 2-101 months, after successful SPKT; mean age 35 years, range 19-56 years; mean duration of diabetes 22 years, range 14-29 years). On addition there was a group (group C) of age- and sex-matched healthy control subjects (n = 14; mean age 35 years, range 23-62 years). PtcO2 measurements included basal recordings at 44 degrees C on the leg and the foot, functional recordings at 44 degrees C after arterial occlusion of the limb for 4 min, measurements during breathing 5 l oxygen per minute and finally while standing up (stand up dP20/dt). All subjects underwent extensive cardiac autonomic testing. In this cross-sectional study the recordings of basal values and of the functional parameters after arterial occlusion and during breathing oxygen did not differ significantly between groups A, B and C.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗