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Biomedical subjects

B Mollenhauer

Publications and source records attributed to B Mollenhauer.

At least 19 recordsLinked to original sources

CSF diagnosis of Alzheimer's disease and dementia with Lewy bodies.

Differential diagnosis of Alzheimer's disease (AD) and dementia with Lewy bodies (DLB) is often crucial. CSF Tau protein and Amyloid-beta (A beta) peptides have shown diagnostic value for the diagnosis of AD, but discrimination from DLB was poor.Herein, we investigate CSF of 18 patients with probable AD, 25 with probable DLB and 14 non-demented disease controls (NDC) by A beta-SDS-PAGE/immunoblot and commercially available ELISAs for A beta1-42 and tau. CSF A beta peptide patterns and tau exhibited disease specific alterations among AD and DLB. The ratio of A beta1-42 to A beta1-38 and A beta1-42 to A beta1-37, respectively, in combination with absolute tau, yielded a sensitivity and specificity of 100 and 92%, respectively. We conclude that CSF A beta peptide patterns and tau levels reflect disease-specific pathophysiological pathways of these dementias as distinct neurochemical phenotypes. Combined evaluation of these biomarkers provides a reasonable accuracy for differential diagnosis of AD and DLB.

Aged↗

[Diagnosis and clinical therapy for Parkinson's disease].

For decades, awareness of Parkinson's disease mainly focused on the presence and treatment of motor symptoms. More and more other symptoms of this disease not related to the motor system now receive increased attention, including cognitive decline. Dementia in Parkinson's disease occurs more often than initially was thought. After an average of 8 years, about 40% of these patients suffer from cognitive decline. The difficulties and related problems affect prognosis more than do the motor symptoms. There is a need for standardized diagnostic and specific therapeutic intervention, but appropriate studies are still lacking.

Algorithms↗

Follow-up investigations in cerebrospinal fluid of patients with dementia with Lewy bodies and Alzheimer's disease.

Measuring proteins in cerebrospinal fluid (CSF) has gained wide acceptance for the differential diagnosis of dementia. Some groups have already extended these investigations in Alzheimer's disease (AD) by asking how stable these markers are in follow-up analysis, if they depend on the stage of disease and whether they can be used to monitor the progression and biological effects of treatment. We evaluated 21 patients with dementia with Lewy bodies (DLB) and 19 patients with AD, on two occasions, with regard to levels of tau protein, tau protein phosphorylated at threonine 181 (p-tau), Abeta42, Abeta40 and S-100B protein, using a set of commercially available assays. Tau protein levels were lower in DLB in first and second LP compared to AD and decreased during course of both groups. P-tau levels were increased in AD and DLB and decreased during follow-up. Abeta42 and Abeta40 remained relatively stable during follow-up but we found a slight increase of the median Abeta42 level in DLB, whereas in AD, Abeta42 tends to decrease during follow-up. S-100B protein increased during follow-up in both diseases. The protein dynamics in DLB and AD are relatively similar. S-100B protein may be a useful marker for follow-up in neurodegenerative diseases but has to be analysed in longer follow-up periods. Tau protein may be used to differentiate between DLB and AD. Follow-up CSF analyses are of limited value for the differentiation of AD and DLB. We conclude that more specific markers have to be established for the differentiation and follow-up of these diseases.

Acetylcholinesterase↗

Sporadic Creutzfeldt-Jakob disease: magnetic resonance imaging and clinical findings.

OBJECTIVE: To assess if clinical features, prion protein codon 129, and molecular subtype correlate with MRI basal ganglia hyperintensity in sporadic Creutzfeldt-Jakob disease (CJD). METHODS: The authors studied 219 patients including 153 confirmed CJD cases for their neurologic symptoms and MRI findings. The MRI was assessed by a blinded investigator for the presence of high signal intensity on T2-weighted images in the basal ganglia. RESULTS: Patients with basal ganglia high signal on T2-weighted images were more likely to present with rapid progressive dementia in an early stage and shorter disease duration (median 6.7 months and 8.6 months). Surprisingly, among the CJD cases, patients without signal increase of the basal ganglia were shown to have a higher frequency of extrapyramidal disturbances (82% vs 70%). More striking differences were found for symptoms such as depression and sensory disturbances, which were more frequent among cases without signal increase. MRI was more likely to be diagnostic in patients with MV2 molecular subtype. CONCLUSIONS: Selected clinical and pathologic features correlate with the presence of basal ganglia high signal on T2-weighted MRI in patients with definite or probable CJD.

Adult↗

[Epidemiology and clinical symptomatology of Creutzfeldt-Jakob disease].

OBJECTIVE: Analogous to prospective studies in other countries, prevalance and symptoms of sporadic Creutzfeldt-Jakob disease (CJD) were recorded in order to assess irregularities in the incidence of the disease in Germany since the onset of bovine spongioform encephalopathy (BSE). PATIENTS AND METHODS: SInce 1993 all suspected case of CJD reported in the Federal Republic of Germany have been analysed by a unified schema and classified by standardised criteria. In addition to voluntary reporting two other systems were accessed: (1) compulsory reporting to the Robert Koch Institute via the appropriate Health Department and (2) cause of death statistics of the Federal Office of Statistics. RESULTS: Between June 1993 and May 2001, a total of 1247 patients with suspected CJD, obtained by the angle quotation mark, rightStudy of the epidemiology and early diagnosis of human spongioform encephalopathiesangle quotation mark, left at Göttingen University, were examined. The suspected disease was confirmed by autopsy in 404 cases, the diagnosis of probable CJD was made in 369 cases on the basis of clinical data and additional investigation. At the beginning of the Göttingen Study in 1993 the incidence in Germany was 0.7 per mill. population, while in the year 2000 it had risen to 1.3 per mill. population. Corresponding increases in the number of cases since 1993 have been noted also by the Robert Koch Institute and the Federal Office of Statistics. CONCLUSIONS: The increased incidence can be explained primarily by a decrease in previously unknown cases. Concerted action as part of the Göttingen Study has increased the cooperation of associated clinics. In addition to sporadic cases of CJD, genetic and, more rarely, iatrogenic forms have been seen in Germany. But no cases of new variant CJD have been reported so far.

Adult↗

Tau protein and 14-3-3 protein in the differential diagnosis of Creutzfeldt-Jakob disease.

BACKGROUND: Diagnosis of Creutzfeldt-Jakob disease (CJD) is made according to the typical clinical picture and can be supported by a positive 14-3-3 CSF immunoblot. Promising results for the diagnostic sensitivity and specificity of tau-protein measurement in CSF already have been described in a smaller group of patients. Both tests in a larger group of patients with the differential diagnosis of CJD were evaluated. METHODS: CSF of 297 patients under the differential diagnosis of CJD (109 definite, 55 probable, 39 possible; 85 others, 1 iatrogenic, 8 genetic), 23 nondemented control subjects, and 15 non-CJD patients with positive 14-3-3 immunoblots were analyzed. The 14-3-3 immunoblot bands were semiquantitatively rated as strong, medium, and weak. Tau-protein was analyzed using a commercially available ELISA. In addition, patients were neuropathologically classified according to prion protein type and polymorphism at codon 129. RESULTS: A diagnostic sensitivity of 94%, a diagnostic specificity of 90%, and a positive predictive value of 92% were achieved for tau-protein at a cut-off of 1,300 pg/mL. These results are comparable with those of the 14-3-3 immunoblot. For patients with type II prion protein and methionine/valine or valine/valine polymorphism at codon 129, tau-protein has a higher diagnostic sensitivity than 14-3-3 protein. Tau-protein levels were significantly higher in patients with higher-rated 14-3-3 immunoblot bands. CONCLUSION: The differential diagnostic significance of the 14-3-3 immunoblot is similar to that of the tau-protein ELISA. The advantage of the tau-protein ELISA is that it is easy to use in routine laboratories. Patients with a negative 14-3-3 immunoblot already have measurable tau-protein levels. This increases information on 14-3-3-negative patients with CJD and especially on patients with other diseases.

14-3-3 Proteins↗

How to improve the clinical diagnosis of Creutzfeldt-Jakob disease.

This paper describes a prospective follow-up of 364 patients initially notified as suspected Creutzfeldt-Jakob disease to a Surveillance Unit in Göttingen, Germany. Six patients were diagnosed as having genetic prion disease by blood analysis and were excluded from the study. After examination and review of the remaining 358, 193 were classified as probable Creutzfeldt-Jakob disease. However, autopsy revealed that five of the 193 did not have Creutzfeldt-Jakob disease (four cases, Alzheimer's disease; one case, cerebral lymphoma). Of the 54 patients classified as possible Creutzfeldt-Jakob disease, 10 had another diagnosis made at autopsy. Two of the 111 cases originally classified as having other diseases were found to have Creutzfeldt-Jakob disease on autopsy. Autopsy evidence, together with follow-up of the patients still living and those who died without autopsy, revealed a broad range of other diagnoses. In the younger age groups, the commonest were chronic inflammatory diseases including Hashimoto encephalitis, whilst rapidly progressive Alzheimer's disease was most common in the older age groups. The presence of 14-3-3 protein in the CSF discriminated better between Creutzfeldt-Jakob disease and other rapidly progressive dementias than did the EEG pattern or the MRI. The inclusion of this CSF protein in the criteria of Masters and colleagues (Ann Neurol 1979; 5: 177-88) improves the accuracy and confidence in the clinical diagnosis of Creutzfeldt-Jakob disease.

14-3-3 Proteins↗

Hashimoto's encephalitis as a differential diagnosis of Creutzfeldt-Jakob disease.

OBJECTIVES: During an epidemiological study of Creutzfeldt-Jakob disease in Germany, Hashimoto's encephalitis was encountered as a differential diagnosis, which has not yet been described in this context. METHODS: The symptoms and findings of seven patients who fulfilled the criteria for "possible" Creutzfeldt-Jakob disease are presented. RESULTS: A Hashimoto's thyroiditis with antibodies against thyroglobulin or thyroid peroxidase, or both and a hypoechoic thyroid ultrasonogram were found in all cases. Analysis of CSF disclosed an increased leucocyte count in three patients, and a raised CSF:serum concentration ratio of albumin (QA1b) in four patients. The 14-3-3 protein, typical of Creutzfeldt-Jakob disease, could not be detected in any of our patients. No periodic sharp wave complexes, which are typical of Creutzfeldt-Jakob disease, were detected on EEG in any of the cases. By contrast with Creutzfeldt-Jakob disease, which leads to death within a few months, the patients with Hashimoto's encephalitis often recover quickly when treated adequately. All the patients improved after administration of corticosteroids. CONCLUSION: The clinical symptomatology of both diseases may be very similar: dementia, myoclonus, ataxia, and personality change or psychotic phenomena are characteristic symptoms.

Adult↗

An aligning auxiliary for ribbon arch brackets: rectangular boxes from ultrafine high tensile wires.

For the last thirty years, those using the ribbon arch brackets have disregarded the control of the apices at the start of treatment, if they have followed Begg principles. This was done for simplicity in teaching especially during the early short courses, and for anchorage purposes, yet Dr Begg's original article showed torquing control early in treatment. The problem of anchorage can now be overcome with the use of extremely light wires for bodily alignment which were not available to Dr Begg. Furthermore, clinical observations by other practitioners have confirmed the author's observation that such extremely light constant forces seem to remodel cortical bone in many patients, such as when instanding lateral incisors are brought forward. The principal reason for presenting this article is the theoretical implication--for orthodontics in general--of the possibility of cortical bone remodelling by fixed appliances. The secondary reason is that it is becoming accepted as a major advance in the Begg appliance.

Humans↗