Botulinum toxin for palmar hyperhidrosis.
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Adult↗
Biomedical subjects
M Naumann
Publications and source records attributed to M Naumann.
Mitochondrial dysfunction with myoclonus epilepsy and ragged-red fibers point mutation in nerve, muscle, and adipose tissue of a patient with multiple symmetric lipomatosis.
We report a 64-year-old man presenting with multiple symmetric lipomatosis (MSL) and mitochondrial encephalomyoneuropathy. The diagnosis of a mitochondrial cytopathy was based on the typical clinical symptoms and signs, including chronic progressive external ophthalmoplegia, hearing impairment, cerebellar ataxia, proximal myopathy, and polyneuropathy, and on molecular genetic and histological examinations. As a unique finding, the A-->G(8344) myoclonus epilepsy and ragged-red fibers point mutation was found in peripheral nerve, muscle, and adipose tissue. Muscle biopsy revealed multiple ragged-red fibers and other morphological signs of a mitochondrial myopathy. Sural nerve biopsy demonstrated a mixed axonal and demyelinating neuropathy with extensive loss of myelinated fibers and conspicuous onion bulb formations, as well as structural mitochondrial abnormalities on electron microscopy. These findings clearly demonstrate mitochondrial dysfunction in muscle, adipose tissue, and for the first time also in nervous tissue of an MSL patient, and strongly support the concept of mitochondrial cytopathy as one of the possible causes of multiple symmetric lipomatosis.
Adipose Tissue↗
Treatment of gustatory sweating with botulinum toxin.
Gustatory sweating is an autonomic disorder that frequently occurs after parotid gland surgery. We investigated the action of intracutaneous injections of botulinum toxin (BTX) (1.0-2.0 mouse units/2.25-cm2 skin area) in 45 patients (mean age, 52 years) with gustatory sweating. The area of hyperhidrosis was determined by Minor's iodine test before and up to 24 weeks after the injection. The effect of BTX was assessed by measuring the hyperhidrotic area. The maximum BTX-induced reduction of gustatory sweating was seen at 7.4 +/- 4.5 days after injection. The area of sweating decreased from 17.6 +/- 8.6 cm2 before BTX to 1.3 +/- 1.6 cm2 after BTX (p < 0.0001). Half the patients rated gustatory sweating subjectively as completely abolished, and the remainder felt pronounced improvement. No toxic effects were observed. In none of the patients did hyperhidrosis recur over a 6-month follow-up. We conclude that BTX is a safe and effective treatment that can be recommended as the therapy of choice in gustatory sweating.
Adult↗
Comparison of transcranial sonography, magnetic resonance imaging, and single photon emission computed tomography findings in idiopathic spasmodic torticollis.
Various lines of evidence suggest that the basal ganglia and thalamus are involved in the pathogenesis of idiopathic dystonia, but unfortunately neuroradiological and pathological data are sparse and controversial. In this study, we have examined 10 patients with spasmodic torticollis by neuroimaging techniques, including transcranial sonography (TS; n = 10), conventional (n = 10) and diffusion-weighted (n = 5) magnetic resonance imaging (MRI), and single photon emission computed tomography (SPECT; n = 10), employing [123I]iodobenzamide (IBZM) as a ligand with a high affinity to the D2 receptor. In seven patients, TS showed small hyperechogenic lesions in the medial segments of the lentiform nucleus contralateral to the side of head deviation. In accordance with the site of TS abnormalities, diffusion-weighted MRI displayed a hyperintense lesion in only one patient, while standard MRI of this area was normal in all patients. SPECT revealed a slight but statistically nonsignificant reduction of IBZM tracer uptake in an area corresponding to the dorsal portions of the striatum in 9 of the 10 patients. TS findings support the hypothesis that structural alternations of the pallidothalamic circuit contralateral to the side of head deviation are involved in the pathogenesis of idiopathic spasmodic torticollis. TS may be more sensitive in detecting basal ganglia alterations than MRI.
Adult↗
[123I]beta-CIT single-photon emission tomography in DOPA-responsive dystonia.
The radiotracer [123I]beta-CIT is a sensitive marker of dopamine uptake sites that can be used to visualize dopaminergic nerve endings in vivo in the human brain. We report on [123I]beta-CIT single-photon emission computed tomography (SPECT) findings in a patient with DOPA-responsive dystonia (DRD). [123I]beta-CIT SPECT showed a striatal radiotracer uptake in the upper range of normal, indicating intact dopamine transporters and structural integrity of nigrostriatal neurons. This differentiates DRD from clinically similar cases with juvenile-onset parkinsonism with dystonia that have a considerable poorer prognosis. [123I]-beta-CIT SPECT may provide a method equally as useful as fluorodopa positron emission tomography in DRD.
Adult↗
Distal muscular dystrophy of Miyoshi type. Report of two cases and review of the literature.
Miyoshi myopathy (MM) is a rare distal myopathy that mainly occurs in Japan. And that is characterized by prominent involvement of the gastrocnemius muscles. Here we report two patients, brother and sister, from a German family. Onset of the disease was at the age of 20 and 22 years, respectively. In both siblings, there was an early and predominant involvement of the gastrocnemius muscles. Creatine kinase activity was elevated 37- to 95-fold above normal. Electromyography revealed fibrillations, positive sharp waves and a myopathic pattern, particularly in the distal muscles of the lower limbs. Histology of the gastrocnemius muscles showed myopathic changes consistent with muscular dystrophy. Occurrence in these two siblings but in no other family members was indicative of an autosomal-recessive inheritance. Our report indicates that MM may also be found in Germany, and that it should be considered in the differential diagnosis of distal myopathies.
Adult↗
[Standardized aerobic walking on the treadmill by healthy probands and patients with mitochondrial and non-mitochondrial myopathies].
Mitochondrial myopathies are characterized by an abnormal aerobic metabolism. The present study examines the serum lactate concentration during standardized aerobic treadmill ergometry and evaluates its relevance for the diagnosis of mitochondrial myopathies. The present study includes 50 volunteers without neuromuscular disorders (control group), 13 patients with mitochondrial, and 14 patients with non-mitochondrial neuromuscular disorders. All members of the control group were able to walk 15 minutes on the treadmill at a constant velocity of at least 5 km/h without exceeding the aerobic threshold (2 mMol/l lactate, venous blood). Ten patients with mitochondrial myopathies and 4 patients with non-mitochondrial myopathies already exceeded the aerobic threshold at walking velocities of 4 or 5 km/h. Though indicating a reduced aerobic endurance, a pathological test result does not prove the diagnosis of a mitochondrial myopathy. Sensitivity and specificity of treadmill ergometry did not differ significantly from those reported for bicycle ergometry. Thus, using the most common aerobic activity in daily life, treadmill ergometry can be considered as an alternative to bicycle exercise tests in the assessment of mitochondrial abnormalities.
Adult↗
Long-latency reflexes of hand muscles in idiopathic focal dystonia and their modification by botulinum toxin.
Long-latency reflexes (LLR) in thenar muscles were elicited by electrical median nerve stimulation in 34 patients with idiopathic focal dystonia and 20 healthy control subjects. Twenty-seven patients had cervical dystonia and seven patients had upper limb dystonia. In about one-quarter of all patients the early LLR (LLR 1, occurring at approximately 40 ms) was abnormal with either increased amplitudes or only unilateral occurrence, mostly on the clinically affected side. Later responses (LLR 2, occurring at approximately 50 ms) were obtained bilaterally in all controls but were reduced or absent in some patients, mostly on the clinically affected side. In 12 dystonia patients, LLR studies were also performed after clinically effective injection of botulinum toxin. Following botulinum toxin treatment there was a significant reduction of LLR 2 amplitudes on the clinically affected side. Our findings suggest a differential involvement of LLR generators in idiopathic dystonia with an antagonism between LLR 1 and LLR 2 on the affected sides. We propose that the reduction of the LLR 2 response may arise from overactivity of the supplementary motor area, confirming the current concept that dystonia results from cortical overflow due to disinhibited thalamocortical pathways projecting to the supplementary motor area. In addition, the dystonic motor pattern seems open to afferent modifications induced by peripheral botulinum toxin treatment.
Adult↗
Parkinson's disease and depression: evidence for an alteration of the basal limbic system detected by transcranial sonography.
OBJECTIVES: Depression is a frequent symptom in Parkinson's disease. Compelling evidence suggests a role of the brainstem in the control of mood and cognition. In patients with unipolar depression transcranial sonography (TS) studies have shown structural alteration of the mesencephalic brainstem raphe which could suggest an involvement of the basal limbic system in the pathogenesis of primary mood disorders. The objective of the present study was to evaluate whether a similar alteration could be found in depressed patients with Parkinson's disease using TS. METHODS: Thirty patients with Parkinson's disease and 30 age and sex adjusted controls were examined by TS. Raphe echogenicity was rated semiquantitatively. The severity of motor symptoms and depression was rated using standard research instruments. RESULTS: Raphe echogenicity was significantly reduced in depressed patients with Parkinson's disease compared with nondepressed patients with Parkinson's disease and control subjects. Raphe echogenicity correlated negatively with degree of motor impairment, and differences in raphe echo between depressed and non-depressed patients with Parkinson's disease were upheld when motor impairment was controlled for. CONCLUSION: These preliminary findings suggest that, as in unipolar depression, a morphological alteration of the brainstem raphe might be involved in the pathogenesis of depression in Parkinson's disease. This raphe alteration may reflect involvement in the basal limbic system in the pathogenesis of secondary depression. This concept is in line with current knowledge on the pathogenesis of both depression in Parkinson's disease and primary depressive disorders.
Aged↗
Differential expression of CD66a (BGP), a cell adhesion molecule of the carcinoembryonic antigen family, in benign, premalignant, and malignant lesions of the human mammary gland.
CD66a, also known as biliary glycoprotein (BGP), is a member of the carcinoembryonic antigen (CEA) family and the human homologue of the rat cell-CAM. There is evidence that aberrant expression or loss of CD66a in tumor tissue is of biological significance. No data about its expression in breast carcinoma cells and only sparse information about the expression of CD66a in normal breast are available thus far. In this study we used monoclonal antibodies to analyze the expression of CD66a and CEA in normal tissue, benign lesions, and in noninvasive and invasive carcinomas of the mammary gland. In normal tissue and benign lesions, CD66a was consistently expressed at the apical sites of epithelial cells and in myoepithelia, whereas CEA was absent or was restricted only to some apical membranes within the ductal tree. The specific staining of myoepithelia was most evident in pseudoinfiltrative radial scars and sclerosing adenosis. However, the apical expression of CD66a disappeared with the development of the malignant phenotype in noninvasive and invasive carcinomas, and changed gradually from low- to high-grade noninvasive carcinomas into a predominant uniform membrane staining all around the atypical cells. CEA expression was irregular in intensity and distribution. The native apical CD66a staining was partially preserved in some highly differentiated invasive carcinomas with a better prognosis, such as tubular and papillary carcinomas. These findings indicate that loss of CD66a expression rather than a change in staining patterns coincides with the development of the malignant phenotype.
Antibodies, Monoclonal↗
Costs of treating dystonias and hemifacial spasm with botulinum toxin A.
Botulinum toxin (BTX) has become a safe and effective therapeutic tool in the treatment of a variety of neurological disorders, especially dystonias. One major disadvantage, however, is the high cost of a single injection of BTX. In this study of 835 patients, we calculated the cost of treatment with BTX serotype A (BTX-A) for different dystonias and hemifacial spasm. The annual expenditure per patient for BTX-A injections in this cohort totalled (mean +/- standard deviation) 1030 Deutschmarks (DM) [1996 values] +/- DM610 [$US570 +/- $US340; 230 +/- 130 pounds sterling (Pound)] for blepharospasm (n = 158), DM1450 +/- DM1520 ($US800 +/- $US830; 310 Pounds +/- 280 Pounds) for craniocervical dystonia (n = 148), and DM1480 +/- DM780 ($US810 +/- $US430; 330 Pounds +/- 180 Pounds) for oromandibular dystonia (n = 16), while the treatment of cervical dystonia consumed DM4590 +/- DM2060 ($US2520 +/- $US1130; 960 Pounds +/- 420 Pounds) [n = 362] per patient. In order to alleviate symptoms in patients with hemifacial spasm (n = 151), DM510 +/- DM270 ($US280 +/- $US150; 110 Pounds +/- 60 Pounds) had to be spent annually. The expenses for surgical therapy for cervical dystonia were DM10,120 +/- DM1900 (n = 54). No major differences concerning expenditure could be found in this study between the 2 available preparations of BTX. However, there appeared to be a lower rate of adverse effects with the Botox formulation, compared with the Dysport formulation, of BTX-A (this difference was statistically significant, i.e. p < 0.001). Although the cost of an individual injection is high, other cost factors also substantially contribute to the societal costs of adult-onset dystonias. Some of these costs may be attenuated with the use of BTX. The subjective and objective relief of these socially devastating and sometimes painful conditions rewards the expenditure associated with the use of BTX-A.
Adult↗
Mitochondrial DNA mutations in multiple symmetric lipomatosis.
Multiple symmetric lipomatosis (MSL) is a rare disorder of middle life characterized by large subcutaneous fat masses around the neck, shoulders and other parts of the trunk. Peripheral neuropathy is a common finding in these predominantly male patients. Employing electrophysiological measures, we found additional signs of central nervous system involvement in a majority of patients. Etiologically, there is an association with mitochondrial dysfunction. In muscle biopsy, we found ragged red fibers in 8 of 12 patients. Molecular genetic analysis revealed multiple deletions of mitochondrial DNA in one patient and the MERRF mutation at nucleotide 8344 in another. In this review, we summarize our clinical, electrophysiological morphological, biochemical and molecular genetic findings in 17 MSL patients, and give a survey of the literature.
Adult↗
Clinical, morphological, biochemical, and neuroradiological features of mitochondrial encephalomyopathies. Presentation of 19 patients.
Nineteen patients (9 females, 10 males) with mitochondrial encephalomyopathies (ME) were studied. The diagnosis was established according to clinical and histopathological criteria. Leading clinical features were chronic progressive external ophthalmoplegia (CPEO) and muscle weakness in 95% of the patients. Pigmentary retinopathy was seen in 63%, and was always associated with CPEO. Hypacusis was present in 47% and cerebellar ataxia in 63% of patients. Clinical or electrophysiological signs of involvement of the central nervous system (CNS) were found in 21% of the patients. In muscle biopsy ragged red fibers were the predominant histopathological findings (100% of the patients), while COX-negative fibers were seen in 74%, deletions of the mitochondrial DNA in 42%, and defects of the respiratory chain in 32% of the patients. Increased blood lactate levels were found in 79% of the patients. Needle electromyography revealed myopathic features in 74%, features of denervation in 16%, and was normal in the remainder. Imaging studies showed cerebral atrophy in 58%, cerebellar atrophy in 16%, and hyperintense lesions of the white matter, pyramidal tract or extrapyramidal system in 16% of the cases. It is concluded that the clinical manifestations of ME can be very variable. Diagnosis of ME should be always considered in young patients presenting with CPEO and muscle weakness. In most cases, diagnosis can be made by a few selected investigations, while detection of genetic abnormalities may lead to the diagnosis in the remaining cases.
Adult↗
Neurotransmitters in CSF of idiopathic adult-onset dystonia: reduced 5-HIAA levels as evidence of impaired serotonergic metabolism.
While several radiological findings point towards the basal ganglia as a possible anatomical site of the lesion in dystonia patients the biochemical basis of the disorder is still unknown. 5-Hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA) levels-the respective metabolites of serotonin and dopamine-were measured in lumbar cerebrospinal fluid (lCSF) of 15 patients with idiopathic adult-onset focal dystonia and in lCSF of 11 controls. 100 microliters lCSF were analyzed for 5-HIAA and HVA by reversed-phase HPLC with electrochemical detection. 5-HIAA levels were significantly reduced in dystonia patients (11.4 micrograms/ml) compared to controls (18.4 ng/ml) (p < 0.02). HVA levels in dystonia patients (30.3 ng/ml) were below control values (41.6 ng/ml) but this finding did not reach statistical significance. Decreased lCSF levels of 5-HIAA suggest an impaired serotonin metabolism in patients with idiopathic adult-onset dystonia. This observation may provide a biochemical basis for a more specific pharmacotherapy in dystonia patients.
Adult↗
Glucocorticoid-sensitive hereditary inclusion body myositis.
We report a hereditary muscle disorder with features of inclusion body myositis (IBM) in two adult sisters with slowly progressive asymmetrical muscle weakness. The findings of light microscopic and ultrastructural investigations of muscle biopsy specimens were consistent with a diagnosis of IBM. Both patients improved and stabilized on immunosuppressive treatment with corticosteroids and azathioprine. This differentiates our patients from other sporadic and familial cases of IBM. Clinical and histological features are described and compared with those of other previously reported families with IBM.
Female↗
Frequent codeletion of p16/MTS1 and p15/MTS2 and genetic alterations in p16/MTS1 in pancreatic tumors.
BACKGROUND & AIMS: Cell-cycle inhibitor and tumor-suppressor gene p16/MTS1 was found to be altered in a variety of human tumors. To directly investigate genetic alterations and expression of p16/MTS1 and p15/MTS2, this study surveyed pancreatic tumors. METHODS: Cell-cycle inhibitors were analyzed for genetic alterations and expression by polymerase chain reaction, DNA sequencing, reverse-transcription polymerase chain reaction, and Western blotting. RESULTS: The analysis of pancreatic adenocarcinoma (19 cell lines and 3 xenografts) for p16/MTS1 and p15/MTS2 revealed homozygous deletions in 10 of 22 cases (46%) (7 cell lines and 3 xenografts) involving both genes. We show in these 7 cell lines as well as in 3 additional cases (10 of 19[53%]) loss of p16/MTS1 transcripts and in 2 further cases (12 of 19 [63%]) mutations leading to the loss of p16 protein. The frequency of mutations in p16/MTS1 was 56% (5 of 9). In contrast to p16/MTS1, p15/MTS2 transcripts were obtained in all cases exhibiting the p15/MTS2 gene (54%). Loss of expression was not observed for p27 and p18. CONCLUSIONS: These results support that loss of p16 function could be involved in pancreatic cancer and may explain at least in part the aggressive behavior of this tumor type.
Adenocarcinoma↗
Lenticular nucleus lesion in idiopathic dystonia detected by transcranial sonography.
We report the transcranial sonography (TCS) findings of the basal ganglia in 86 patients with dystonic disorders including idiopathic dystonia (facial, cervical, upper limb, and generalized dystonia), drug-induced tardive dystonia, dopa-responsive dystonia, and kinesigenic dystonia. The TCS was focused on alterations of the lenticular, caudate, raphe nuclei, and the thalamus. Seventy-five percent of patient with idiopathic cervical and 83% of those with idiopathic upper limb dystonia had a hyperechogenic lesion of the middle segment of the lenticular nucleus on the side opposite to the clinical dystonic symptoms. The ipsilateral side was also affected in 20%. In facial dystonia, only one-third of the patients revealed lenticular nucleus lesions. The mean area of the lenticular nucleus lesion opposite to the clinically affected side was 30 mm2 in cervical dystonia, 17 mm2 in upper limb dystonia, and 7.5 mm2 in facial dystonia. These lenticular abnormalities were significantly more frequent (p < 0.001) and their areas were significantly greater (p < 0.001) compared with a control group of 50 patients afflicted with radiculopathy. There was a significant correlation of the severity of symptoms with the intensity of lenticular nucleus hyperechogenicity in patients with cervical and upper limb dystonia (p < 0.05). Increased caudate nucleus echogenicity was present in 20% of patients with cervical and upper limb dystonia, mostly contralateral to the clinically affected side and raphe abnormalities were present in 7% of all patients with idiopathic dystonia. In contrast, there were no abnormalities of the lenticular nucleus or thalamus in nonidiopathic dystonias. We conclude that idiopathic dystonia is associated with lesions in the basal ganglia, particularly the lenticular nucleus, that can be visualized by TCS. An alteration of the basal ganglia matrix may be the pathologic basis of idiopathic dystonia with secondary affliction of striatopallidothalamic pathways.
Adult↗
Improved purification of ribulose 5-phosphate 3-epimerase from Saccharomyces cerevisiae and characterization of the enzyme.
D-Ribulose 5-phosphate 3-epimerase from Saccharomyces cerevisiae was purified to homogeneity by 1970-fold enrichment elaborating the following steps: disruption of fresh cells, polyethylene glycol precipitation, ion exchange chromatography, heat-treatment, size exclusion chromatography on Sephadex G-75 and Bio-Sil SEC 125 and hydrophobic interaction chromatography. A molecular mass of 50 +/- 4 kDa was determined for the native enzyme by sedimentation equilibrium experiments. Sodium dodecyl sulfate polyacrylamide gel electrophoresis revealed a single band with 26 kDa which has been characterized as an individual polypeptide chain. Thus, the enzyme is a dimer composed of two identical subunits. The specific activity of the purified enzyme with 7700 units/mg protein was found to be 30-fold higher than described in previous papers. The enzyme shows a hyperbolic dependence of the catalytic activity towards ribulose 5-phosphate with a KM-value of 1.5 mmol/l. The N-terminal amino acid sequence analysis of the native enzyme and of several peptides obtained by chemical and proteolytic fragmentation provided a part of the primary structure which fits to the primary structure deduced from the DNA sequence.
Amino Acid Sequence↗