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Biomedical subjects

M Naumann

Publications and source records attributed to M Naumann.

At least 37 records · Page 2Linked to original sources
PubMed2003

Botulinum toxin type a is a safe and effective treatment for axillary hyperhidrosis over 16 months: a prospective study.

OBJECTIVE: To evaluate the safety and efficacy of botulinum toxin type A (BTX-A) (BOTOX) over 16 months in the treatment of bilateral primary axillary hyperhidrosis. DESIGN: A 16-month study with initial double-blind randomization to 50 U of BTX-A or placebo per axilla. After 4 months, participants could receive up to 3 further treatments with open-label BTX-A over 12 months. SETTING: Fourteen dermatology or neurology clinics in Germany, Belgium, and the United Kingdom. PARTICIPANTS: Of 207 individuals aged between 17 and 74 years who had persistent bilateral primary axillary hyperhidrosis that interfered with daily activities, 174 (84%) completed the study. The baseline gravimetric assessment was a spontaneous sweat production of 50 mg or greater in each axilla prior to initial treatment. MAIN OUTCOME MEASURES: At week 4 after each treatment, the response rate of subjects who had at least a 50% reduction from baseline in axillary sweating, as measured by gravimetric assessment, was evaluated. Adverse events were spontaneously reported throughout the study, together with quality-of-life parameters and assessment of neutralizing antibodies to BTX-A. RESULTS: Over the 16-month period, 356 BTX-A treatments were given to 207 subjects. After placebo treatment, the response rate at week 4 was 34.7%. After the first, second, and third treatment with BTX-A, response rates at week 4 were 96.1%, 91.1%, and 83.3%, respectively. For subjects receiving more than 1 treatment, the mean duration between BTX-A treatments was approximately 7 months; however, 28% of subjects completed the study after only 1 BTX-A treatment. Subjects' satisfaction after treatments was consistently high, their quality of life improved, and there was a reduction in the impact of the disease on their lives. The safety profile of BTX-A after repeated treatments was excellent and no confirmed positive results for neutralizing antibodies to BTX-A occurred. CONCLUSION: Repeated intradermal injections of BTX-A over 16 months for treatment of primary axillary hyperhidrosis is safe and efficacious.

Adolescent↗
PubMed2003

Differentiation of parkinsonian syndromes according to differences in executive functions.

Groups of patients with Parkinson's disease (PD), striatonigral degeneration-type multiple system atrophy (MSA) or progressive supranuclear palsy (PSP) with motor disability stages II and III according to Hoehn and Yahr, and a healthy control group were compared using neuropsychological tests of executive functions. The results indicate that all three patient groups were impaired in the tests of executive functions. In comparison with healthy subjects, the three patient groups showed impaired performance regarding verbal fluency, problem solving and verbal and figural working memory. Patients with PD differed significantly from healthy subjects in a test of verbal recency, while patients with MSA or PSP were unimpaired. The comparison of patient groups revealed no differences between PD and MSA patients. However, patients with PSP showed greater impairment in both phonemic and semantic fluency than patients with PD or MSA. Using discriminant function analysis, it was found that variables derived from four verbal fluency tasks (simple and alternate semantic and phonemic fluency) discriminated among the three patient groups at a level significantly exceeding chance. Over 90% of patients with PSP were correctly classified. Patients with PD and MSA were correctly classified in over 70% of cases. These results suggest that verbal fluency tasks may be sensitive measures in the differential diagnosis of PD, MSA and PSP.

Aged↗
PubMed2003

Botulism type B presenting as pure autonomic dysfunction.

Botulism nowadays is a rare mostly food-borne disease caused by the toxin of Clostridium botulinum. On the other hand, botulinum toxin blocking cholinergic transmission has become a most powerful treatment option for many focal movement disorders and is increasingly used to treat autonomic disorders [2, 7, 8]. Although muscle weakness is the hallmark of botulism, autonomic dysfunction may be the leading clinical symptom in rare cases and should be included in the differential diagnosis of pure dysautonomia. Here, we describe a patient with autonomic dysfunction as the leading symptom of botulism type B.

Adult↗
PubMed2002

Disease progression in amyotrophic lateral sclerosis: predictors of survival.

Predicting the rate of disease progression has become important as trials of new medical treatments for amyotrophic lateral sclerosis (ALS) are planned. Bulbar onset, early impairment of forced vital capacity, and older age have all been associated with shorter survival. We performed a retrospective study to compare survival factors with disease progression in a German ALS population. We analyzed disease progression in 155 patients at intervals of 4 months over a period of 3 years. To evaluate disease progression, the ALS functional rating scale (ALS-FRS), forced vital capacity (FVC%), and a Medical Research Council (MRC) compound score based on a nine-step modified MRC scale were used. We compared age (< 55 years vs. > or =55 years), different sites of disease onset (bulbar vs. limb), and gender to the rate of disease progression and performed survival analyses. No overall significant difference could be detected when analyzing these subgroups with regard to disease progression. By contrast, significantly longer survival was observed in the younger age group (56 months vs. 38 months, P < 0.0001) and in patients with limb-onset disease (51 months vs. 37 months, P = 0.0002). Using Cox analyses values we found that the declines of ALS-FRS, FVC%, and MRC compound score were predictive of survival (P < 0.0001, P = 0.002, and P = 0.003, respectively). Future studies are needed to clarify whether nonspecific factors including muscle atrophy, dysphagia, and coexisting diseases influence prediction of survival in ALS patients. A more precise set of predictors may help to better stratify patient subgroups for future treatment trials.

Age of Onset↗
PubMed2002

A randomized, double-masked, crossover comparison of the efficacy and safety of botulinum toxin type A produced from the original bulk toxin source and current bulk toxin source for the treatment of cervical dystonia.

In 1997, the US FDA approved a new bulk toxin source (now referred to as current) for the manufacture of botulinum toxin type A (BTX-A). The current BTX-A preparation has a lower neurotoxin complex protein load than the original BTX-A preparation, which may reduce antigenic potential. The present double-masked, multicenter study compared the efficacy and safety of BTX-A (BOTOX) produced from both original and current bulk toxin sources for the treatment of cervical dystonia. Patients (N = 133) were injected with BTX-A produced from original and current bulk toxin sources using a crossover design. Adverse events were assessed at each visit. Efficacy was assessed at 2 and 6 weeks post-injection using the severity and pain-disability subscales of the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS). Mean BTX-A doses were comparable (original: 155 U, current: 156 U). Both BTX-A preparations produced similar, statistically significant reductions in TWSTRS severity and pain-disability scores at weeks 2 and 6 post-injection. The original and current BTX-A preparations showed no significant differences in adverse events, including both treatment-related (34%, 31%) and treatment-unrelated (27%, 32%), respectively. BTX-A produced from the original and current bulk toxin sources showed comparable efficacy and safety in the treatment of cervical dystonia; both significantly reduced dystonia severity and pain.

Botulinum Toxins, Type A↗
PubMed2002

[Thrombocytic serotonin concentration in depressed children and adolescents].

OBJECTIVES: This study pursued the question to what extent a correlation exists between the platelet serotonin concentration and depressive and/or suicidal behaviour in children and adolescents. METHODS: Within a 16-month period, the platelet serotonin concentration was determined in all admitted inpatients (n = 145, age: 4 to 19 years) by means of fluorescent spectroscopy according to a standardised protocol. The severity of depressive symptoms was assessed by administration of the DIKJ to a subset of patients. The different diagnostic groups were formed according to the criteria of the ICD-10. RESULTS: A decrease in the platelet serotonin concentration was found with increasing age. While platelet serotonin concentrations were higher in male patients than in females, the girls showed higher depression scores on the DIKJ. A negative correlation existed between the platelet serotonin concentration and the degree of depression measured on the DIKJ in all diagnostic groups. Independent of the clinical diagnosis significantly lower concentrations of platelet serotonin were found in children and adolescents who had attempted suicide immediately before admission to hospital. The same is true for the group of depressive disorders, with a subgroup of patients who had attempted suicide shortly before also showing significantly lower concentrations of platelet serotonin. CONCLUSIONS: The present investigation supports the contention that depression in childhood and adolescence is related to a lack of serotonin in platelets, respectively, analogous to the platelet model, to a lack of serotonin in central structures, and that a relative serotonin deficiency could thus be an indicator of suicidal ideation.

Adolescent↗
PubMed2002

Progressive sudomotor dysfunction in amyotrophic lateral sclerosis.

Autonomic dysregulation is part of the complex degenerative process in amyotrophic lateral sclerosis (ALS). To investigate this, sweating was examined at rest in 39 patients with ALS in comparison with a control group. Sweat was collected over a 30 second period over the thenar and hypothenar eminences and on the sole of the foot, using a commercial device based on vapour pressure gradient. The measurements were repeated after three and six months in 10 patients for longitudinal analysis. In early ALS, patients had significantly higher skin water loss than control subjects over the thenar and the hypothenar eminences. In advanced disease stages, sweating was decreased at all sites compared with controls. A significant decline in sweat secretion of about 40% was found over a six month period. The findings suggest an abnormal sympathetic activity with hyperhidrosis in early ALS and a reduction in sweat production as the disease progresses.

Adult↗
PubMed2001

Evidence for disturbances of copper metabolism in dystonia: from the image towards a new concept.

The pathogenesis of idiopathic adult onset dystonia (ID) is still unclear. Although neuropathologic studies did not reveal consistent abnormalities, electrophysiologic and neuroimaging findings point toward a disinhibition and overactivity of the frontal motor cortical areas caused by an altered basal ganglia outflow. The lentiform nuclei are assumed to play a major role in this scenario. Recent neurochemical analysis of brain tissue stimulated by transcranial ultrasound studies demonstrated an increased copper content of the lentiform nuclei in patients with ID. The shift of brain copper level may substantially influence neuronal activity causing a reduced inhibitory output from the lentiform nuclei to the motor cortex. The reason for the presumably altered copper metabolism is not clear, but preliminary findings suggest that reduced levels of the Menkes protein, a membrane ATPase exporting copper out of the cells, may be implicated. Disturbances of brain copper metabolism may explain various phenomena of ID; however, it needs to be determined whether these observations represent the basic pathogenetic mechanism of ID or reflect another as yet unidentified pathologic process.

Basal Ganglia↗
PubMed2001

The constitutive photomorphogenesis 9 signalosome directs vascular endothelial growth factor production in tumor cells.

Angiogenesis is a prerequisite for solid tumor growth and metastasis. Elucidation of the signaling pathways that control tumor angiogenesis constitutes the basis for a rational antiangiogenic tumor therapy. Here we show that the production of vascular endothelial growth factor (VEGF) in HeLa and HL-60 cells is directed by the constitutive photomorphogenesis 9 signalosome (CSN). The CSN is a kinase complex that cooperates with the ubiquitin/26S proteasome system in regulating the stability of proteins involved in signal transduction. VEGF expression is controlled by the transcription factors activator protein (AP)-1, AP-2, SP-1, and hypoxia-inducible factor 1. Inhibition of CSN kinase activity by 50 microM curcumin for 2 h decreases the cellular c-Jun concentration, resulting in a reduction of the VEGF production by approximately 75%. The removal of the inhibitor from the cells led to a time-dependent recovery of endogenous c-Jun that is paralleled by increasing VEGF production. Elevated cellular CSN activity induced by CSN subunit 2 overexpression causes increased VEGF production in HeLa cells. A competitor of CSN-dependent c-Jun phosphorylation, the NH(2)-terminal c-Jun fragment Deltac-Jun(1-226), inhibits VEGF production in HeLa cells. The transcription factors AP-2 and SP-1 act independently of the CSN. They contribute less than a quarter to basal VEGF production. Under our experimental conditions, hypoxia-inducible factor 1alpha protein was not detected. Overexpression of the tumor suppressor p53 reduces VEGF production in HeLa cells. p53 competes with c-Jun for CSN-specific phosphorylation with the consequence of c-Jun destabilization. We conclude that CSN-directed c-Jun signaling mediates high VEGF production in HeLa and HL-60 cells. The data provide an explanation for the known antiangiogenic and antitumorigenic activities of curcumin. Because the CSN regulates the major part of VEGF production in the tested tumor cells, it constitutes a potentially important target for tumor therapy.

COP9 Signalosome Complex↗
PubMed2001

Botulinum toxin type A in treatment of bilateral primary axillary hyperhidrosis: randomised, parallel group, double blind, placebo controlled trial.

OBJECTIVES: To evaluate the safety and efficacy of botulinum toxin type A in the treatment of bilateral primary axillary hyperhidrosis. DESIGN: Multicentre, randomised, parallel group, placebo controlled trial. SETTING: 17 dermatology and neurology clinics in Belgium, Germany, Switzerland, and the United Kingdom. PARTICIPANTS: Patients aged 18-75 years with bilateral primary axillary hyperhidrosis sufficient to interfere with daily living. 465 were screened, 320 randomised, and 307 completed the study. INTERVENTIONS: Patients received either botulinum toxin type A (Botox) 50 U per axilla or placebo by 10-15 intradermal injections evenly distributed within the hyperhydrotic area of each axilla, defined by Minor's iodine starch test. MAIN OUTCOME MEASURES: Percentage of responders (patients with >/=50% reduction from baseline of spontaneous axillary sweat production) at four weeks, patients' global assessment of treatment satisfaction score, and adverse events. RESULTS: At four weeks, 94% (227) of the botulinum toxin type A group had responded compared with 36% (28) of the placebo group. By week 16, response rates were 82% (198) and 21% (16), respectively. The results for all other measures of efficacy were significantly better in the botulinum toxin group than the placebo group. Significantly higher patient satisfaction was reported in the botulinum toxin type A group than the placebo group (3.3 v 0.8, P<0.001 at 4 weeks). Adverse events were reported by only 27 patients (11%) in the botulinum toxin group and four (5%) in the placebo group (P>0.05). CONCLUSION: Botulinum toxin type A is a safe and effective treatment for primary axillary hyperhidrosis and produces high levels of patient satisfaction.

Adolescent↗
PubMed2001

Pathogenic Neisseria trigger expression of their carcinoembryonic antigen-related cellular adhesion molecule 1 (CEACAM1; previously CD66a) receptor on primary endothelial cells by activating the immediate early response transcription factor, nuclear factor-kappaB.

Neisseria gonorrhoeae express opacity-associated (Opa) protein adhesins that mediate binding to various members of the carcinoembryonic antigen-related cellular adhesion molecule (CEACAM; previously CD66) receptor family. Although human umbilical vein endothelial cells express little CEACAM receptor in vitro, we found neisserial infection to induce expression of CEACAM1, CEACAM1-3L, and CECAM1-4L splice variants. This mediates an increased Opa(52)-dependent binding of gonococci by these cells. The induced receptor expression did not require bacterial Opa expression, but it was more rapid with adherent bacteria. Because the time course of induction was similar to that seen for induced proinflammatory cytokines, we tested whether CEACAM1 expression could be controlled by a similar mechanism. Gonococcal infection activated a nuclear factor-kappaB (NF-kappaB) heterodimer consisting of p50 and p65, and inhibitors that prevent the nuclear translocation of activated NF-kappaB complex inhibited CEACAM1 transcript expression. Each of these effects could be mimicked by using culture filtrates or purified lipopolysaccharide instead of intact bacteria. Together, our results support a model whereby the outer membrane "blebs" that are actively released by gonococci trigger a Toll-like receptor-4-dependent activation of NF-kappaB, which up-regulates the expression of CEACAM1 to allow Opa(52)-mediated neisserial binding. The regulation of CEACAM1 expression by NF-kappaB also implies a broader role for this receptor in the general inflammatory response to infection.

Antigens, Bacterial↗
PubMed2001

Regulation of phosphotransferase activity of hexokinase 2 from Saccharomyces cerevisiae by modification at serine-14.

Isoenzyme 2 of hexokinase functions in sugar sensing and glucose repression in Saccharomyces cerevisiae. The degree of in vivo phosphorylation of hexokinase 2 at serine-14 is inversely related to the extracellular glucose concentration [Vojtek, A. B., and Fraenkel, D. G. (1990) Eur. J. Biochem. 190, 371-375]; however, a physiological role of the modification causing the dissociation of the dimeric enzyme in vitro [as effected by a serine-glutamate exchange at position 14; Behlke et al. (1998) Biochemistry 37, 11989-11995] is unclear. This paper describes a comparative stopped-flow kinetic and sedimentation equilibrium analysis performed with native unphosphorylated hexokinase 2 and a permanently pseudophosphorylated glutamate-14 mutant enzyme to determine the functional consequences of phosphorylation-induced enzyme dissociation. The use of a dye-linked hexokinase assay monitoring proton generation allowed the investigation of the kinetics of glucose phosphorylation over a wide range of enzyme concentrations. The kinetic data indicated that monomeric hexokinase represents the high-affinity form of isoenzyme 2 for both glycolytic substrates. Inhibition of glucose phosphorylation by ATP [Moreno et al. (1986) Eur. J. Biochem. 161, 565-569] was only observed at a low enzyme concentration, whereas no inhibition was detected at the high concentration of hexokinase 2 presumed to occur in the cell. Pseudophosphorylation by glutamate substitution for serine-14 increased substrate affinity at high enzyme concentration and stimulated the autophosphorylation of isoenzyme 2. The possible role of hexokinase 2 in vivo phosphorylation at serine-14 in glucose signaling is discussed.

Amino Acid Substitution↗
PubMed2001

Helicobacter pylori-induced prostaglandin E(2) synthesis involves activation of cytosolic phospholipase A(2) in epithelial cells.

Helicobacter pylori initiates an inflammatory response and gastric diseases, which are more common in patients infected with H. pylori strains carrying the pathogenicity island, by colonizing the gastric epithelium. In the present study we investigated the mechanism of prostaglandin E(2) (PGE(2)) synthesis in response to H. pylori infection. We demonstrate that H. pylori induces the synthesis of PGE(2) via release of arachidonic acid predominately from phosphatidylinositol. In contrast to H. pylori wild type, an isogenic H. pylori strain with a mutation in the pathogenicity island exerts only weak arachidonic acid and PGE(2) synthesis. The H. pylori-induced arachidonic acid release was abolished by phospholipase A(2) (PLA(2)) inhibitors and by pertussis toxin (affects the activity of G alpha(i)/G alpha(o)). The role of phospholipase C, diacylglycerol lipase, or phospholipase D was excluded by using specific inhibitors. An inhibitor of the stress-activated p38 kinase (SB202190), but neither inhibitors of protein kinase C nor an inhibitor of the extracellular-regulated kinase pathway (PD98059), decreased the H. pylori-induced arachidonic acid release. H. pylori-induced phosphorylation of p38 kinase and cytosolic PLA(2) was blocked by SB202190. These results indicate that H. pylori induces the release of PGE(2) from epithelial cells by cytosolic PLA(2) activation via G alpha(i)/G alpha(o) proteins and the p38 kinase pathway.

Arachidonic Acid↗
PubMed2001

Measurement of the midbrain diameter on routine magnetic resonance imaging: a simple and accurate method of differentiating between Parkinson disease and progressive supranuclear palsy.

Anteroposterior diameters of the suprapontine midbrain, the pons, and the collicular plate were measured in 50 patients with various parkinsonian syndromes (Parkinson disease [PD] [n = 20], progressive supranuclear palsy [PSP] [n = 16], and multiple-system atrophy of striatonigral type [n = 14]) and 12 age-matched healthy control subjects by means of axial T2-weighted magnetic resonance images. While no differences in midbrain diameter were found between patients with PD (mean, 18.5 mm) and control subjects (mean, 18.2 mm), patients with PSP had significantly lower midbrain diameters (mean, 13.4 mm) than patients with PD and control subjects (P<.001), without any overlap between these 2 groups. However, midbrain diameters of patients with multiple-system atrophy were also significantly lower than those of control subjects and patients with PD, with individual values showing overlap with the PSP, PD, and control groups. Pontine and collicular plate diameters did not contribute additional information. We therefore conclude that measurement of anteroposterior diameter of the midbrain on axial T2-weighted magnetic resonance images is a reliable means to differentiate patients with PSP from those with PD and should be incorporated into the diagnostic criteria for PSP.

Aged↗
PubMed2001

Inherited Myoclonus-dystonia syndrome: narrowing the 7q21-q31 locus in German families.

Genetic studies were performed in four German families with autosomal dominant myodonus-dystonia syndrome. Mutations in the D2 dopamine receptor gene, which have been implicated in this disorder, were excluded in all four families by linkage analysis and direct sequencing. All four families supported linkage to the second reported locus on chromosome 7q21 with a combined maximum multipoint lod score of 5.99. The observation of key recombinations in one family refined the disease locus to a 7.2 cM region flanked by the markers D7S652 and D7S2480.

Adolescent↗
PubMed2001

Cervical dystonia in monozygotic twins: case report and review of the literature.

We report on monozygotic male twins of German origin with early onset cervical dystonia. No other family members were affected. Although identical in age of onset and clinical course, there were phenotypic variations. While the second-born, more affected twin suffered from a symmetric retrocollis, the twin brother mainly presented with a spasmodic torticollis to the left. Dystonia remained focal in both siblings. A DYT1 gene deletion was excluded. Including our patients, hitherto only four twin pairs with idiopathic dystonia have been reported. Although dystonia in twins can be remarkably uniform in some cases, major differences in terms of disease progression, remissions, and disability may be found. These observations underline the role of inheritance in the pathogenesis of idiopathic dystonia but also indicate that some other factors contribute to the clinical presentation of dystonia.

Adult↗
PubMed2001

Evidence-based medicine: botulinum toxin in focal hyperhidrosis.

All studies performed so far indicate that BTX-A is a safe and effective treatment for focal hyperhidrosis of the axillae and palms, for gustatory sweating, and for some other rare conditions associated with focal hyperhidrosis. Based on two large well-designed, double-blind, placebo-controlled study there is class 1 evidence for the efficacy of BTX-A in axillary hyperhidrosis, and class 2 evidence for BTX-A in gustatory and palmar sweating (classification according to the Quality Standards Subcommittee of the American Academy of Neurology, 1994). Other indications (forehead sweating, plantar hyperhidrosis, truncal sweating) are only anecdotally reported.

Animals↗