In vivo requirement of TGF-β/GDNF cooperativity in mouse development: focus on the neurotrophic hypothesis

Neurotrophic factors are well-recognized extracellular signaling molecules that regulate neuron development including neurite growth, survival and maturation of neuronal phenotypes in the central and peripheral nervous system. Previous studies have suggested that TGF-β plays a key role in the regulation of neuron survival and death and potentiates the neurotrophic activity of several neurotrophic factors, most strikingly of GDNF. To test the physiological relevance of this finding, TGF-β2/GDNF double mutant (d-ko) mice were generated. Double mutant mice die at birth like single mutants due to kidney agenesis (GDNF−/−) and congential cyanosis (TGF-β2−/−), respectively. To test for the in vivo relevance of TGF-β2/GDNF cooperativity to regulate neuron survival, mesencephalic dopaminergic neurons, lumbar motoneurons, as well as neurons of the lumbar dorsal root ganglion and the superior cervical ganglion were investigated. No loss of mesencephalic dopaminergic neurons was observed in double mutant mice at E18.5. A partial reduction in neuron numbers was observed in lumbar motoneurons, sensory and sympathetic neurons in GDNF single mutants, which was further reduced in TGF-β2/GDNF double mutant mice at E18.5. However, TGF-β2 single mutant mice showed no loss of neurons. These data point towards a cooperative role of TGF-β2 and GDNF with regard to promotion of survival within the peripheral motor and sensory systems investigated.     

ATP13A2 variants in early‐onset Parkinson's disease patients and controls

Four genes responsible for recessively inherited forms of Parkinson's disease (PD) have been identified, including the recently discovered ATP13A2 (PARK9) gene. Our objective was to investigate the role of this gene in a large cohort of PD patients and controls. We extensively screened all 29 exons of the ATP13A2 coding region in 112 patients with early‐onset PD (EOPD; <40 years) of mostly European ethnic origin and of 55 controls. We identified four carriers (3.6%) of novel single heterozygous ATP13A2 missense changes that were absent in controls. Interestingly, the carrier of one of these variants also harbored two mutations in the Parkin gene. None of the carriers had atypical features previously described in patients with two mutated ATP13A2 alleles (Kufor–Rakeb syndrome). Our data suggest that two mutated ATP13A2 alleles are not a common cause of PD. Although heterozygous variants are present in a considerable number of patients, they are—based on this relatively small sample—not significantly more frequent in patients compared to controls. © 2009 Movement Disorder Society     

A cross-sectional study of quality of life in incident stroke survivors in rural northern Tanzania

The aim of this study was to evaluate changes to, and predictors of, quality of life (QOL) in a community-based cohort of stroke survivors from an earlier stroke incidence study in rural northern Tanzania. Patients were assessed 1–5 years after their incident stroke. The study cohort was compared with an age- and sex-matched control group from the same rural district within a cross-sectional design. Patients and controls were asked a series of questions relating to their QOL [World Health Organization quality of life, abbreviated version (WHOQOL-BREF)], levels of anxiety and depression [hospital anxiety and depression (HAD) scale], cognitive function [community screening instrument for dementia (CSI-D) screening tool], socioeconomic status and demographic characteristics (e.g. age, sex, education and abode). Patients were further assessed for functional outcome and disability (Barthel index, modified Rankin scale), post-stroke care and psychosocial functioning. Patients (n = 58) were found to have significantly lower QOL than controls (n = 58) in all six domains of the WHOQOL-BREF. Gender, socioeconomic status, cognitive function and time elapsed since stroke were not associated with QOL. Older patients and those with more impaired motor function and disability (Barthel index, modified Rankin score) had significantly poorer physical health-related QOL. Greater anxiety and depression, reduced muscle power and less involvement in social events were significantly correlated with lower physical and psychological health-related QOL. To our knowledge, this is the first long-term study of QOL in survivors of incident stroke in Sub-Saharan Africa (SSA). Poorer QOL was associated with greater levels of physical disability, anxiety and depression and reduced social interaction. Demographic factors appear to be much less significant. Modifying these QOL predictors could be important in planning effective post-stroke care within a stretched healthcare system.     

Arsen — Leber — Tumoren

Ohne ZusammenfassungMit 12 Textabbildungen     

Air-exposed tissue culture of human middle ear epithelium and meatal epidermis: a method to study the advancing front of cholesteatoma

The suitability of an air-exposed culture model consisting of a collagen matrix was investigated for constructing an advancing front (AF) of human middle ear epithelium (MEE) and meatal epidermis (ME). Three different culture settings were used: (i ) MEE; (ii) ME; and (iii) AF (MEE + ME). Small tissue biopsies were placed on a fibroblast-populated collagen matrix and grown at the air-liquid interface. After 3 weeks of culture, the MEE and ME outgrowth was differentiated. Light, scanning electron and transmission electron microscopy showed no visible differences compared to native MEE and ME. Cytokeratin 8 and cytokeratin 10 expressions were comparable to the expression seen in the native MEE and ME tissues. Proliferation, which was demonstrated by the expression of Ki-67, was present in the basal layers of cultured MEE and ME. A double layer of cells in which the ME covered the MEE formed the AF. In the AF, the MEE and ME showed the same morphological and immunohistochemical characteristics as in their native tissues. The results of the study show that this in vitro system is a well-defined model system offering the possibility to study the effects of external stimuli on the different epithelia of the AF involved in the pathogenesis of cholesteatoma.     

St. Francis came at dawn--the miraculous recovery of a hemiplegic monk in the Middle Ages

We present the English translation of a remarkable case report from the 13th century. A collection of miracles ascribed to St. Francis contains the story of a young monk suddenly afflicted by a neurological disorder characterized by hemiplegia, speech problems and confusion. St. Francis' appearance led to complete recovery. From a theological and literary point of view, the text includes many allusions to the miracles performed by Jesus and to pagan traditions from Asclepius to Ovid. Retrospective neurological diagnoses range from a prolonged ischemic neurological deficit (PRIND) to psychogenesis. This case history is a rare example of faith healing in its contemporary context.     

Sleep complaints and visual impairment among older Americans: a community-based study

BACKGROUND: This report describes the associations between sleep complaints and reported visual impairment in an urban community-residing older adult sample. METHODS: A total of 1118 volunteers from a biracial cohort participated in the study (mean age = 74 +/- 6; mean body mass index = 28 +/- 10). Volunteers were recruited using a stratified, cluster sampling technique. In a standard order, several questionnaires were administered, soliciting information on socioeconomic status, physical health, social support, and emotional experience. The physical health questionnaire included questions on whether or not the volunteer experienced sleep disorder, visual impairment, heart disease, respiratory disease, arthritis, and hypertension. In this report, we present data on the prevalence of reported sleep problems and visual impairment among older adults. RESULTS: Of the total sample, 9% used sleep medicine, 25% reported difficulty falling asleep, 52% indicated experiencing difficulty maintaining sleep, 28% reported waking up early in the morning, and 12% reported daytime sleep longer than 2 hours. Chi-square results showed greater sleep complaints for volunteers with visual impairment. Consistent with these results, analysis of variance revealed that visually impaired volunteers had a higher index rate of sleep disturbance (F((1, 1110)) = 35.32, p <.0001). CONCLUSIONS: These data provide evidence that older adults reporting visual impairment are also likely to report sleep complaints. This verifies laboratory findings of an association of ophthalmic diseases with sleep-wake problems and with circadian rhythm abnormalities.     

Contemporary treatment of heart failure: Is there adequate evidence to support a unique strategy for African-Americans? con position

Heart failure is a substantial cause of increased morbidity and mortality in the African-American population, with poorer prognosis versus white patients. Systolic heart failure is predominantly caused by poorly controlled hypertension in African-Americans. Overall, African-Americans remain underrepresented in morbidity and mortality heart failure trials, and further data are needed to confirm the potential benefit of present therapies and newer approaches to heart failure in African-Americans. Intensive blood pressure control and control of other risk factors, along with the appropriate application of evidence-based therapies including angiotensin converting enzyme (ACE) inhibitors and approved beta-blockers, are required to decrease racial disparities. Although some data suggest that contemporary treatment with ACE inhibitors and beta-blockers may be less effective in African-Americans in terms of reducing heart failure morbidity and mortality, there is not adequate evidence to support a unique strategy for this population. The use of evidence-based therapies should be equally applied to African-Americans as well as to other ethnic groups while awaiting further studies.     

Dead Sea treatment - principle for outpatient use in atopic dermatitis: safety and efficacy of synchronous balneophototherapy using narrowband UVB and bathing in Dead Sea salt solution

Safety and efficacy of this new treatment modality for out-patients were evaluated by an uncontrolled multicenter trial under GCP-conditions. Patients had to undergo 3-5 treatment sessions per week up to 35 in total. SCORAD (SC) was assessed at baseline, after 20 and 35 sessions. For patients with early study withdrawal the last-observation-carry-forward-principle was used. 615 intention-to-treat (itt)- (baseline SC: 59.4) and 143 according-to-protocol (atp)-patients (baseline SC: 60.1) could be analysed. 289 patients (47%) (baseline SC: 59.1) underwent less than 35 sessions. Main reasons were: lack of time (16%), non-compliance (12%), good improvement (7%), lack of efficacy (6%), intercurrent disease (4%) and side effects (3%). Mean number of sessions in atp-group was 35, in itt 26, and in patients with early study withdrawal 15.8. SC decreased in atp-group to 37.5 (itt: 44.5/patients with early study withdrawal: 46.1) after 20 sessions and to 27.1 (35.2/42.6) at end of treatment. Relative SC-improvement was statistically significant in atp- (55%), itt-group (41%), and in patients with early study withdrawal (26%). Most frequent side effects were: erythema in 7.3%, burning of skin due to salt solution in 3.6%. Safety and efficacy could be proven in both atp- and itt-group. A marked difference in efficacy between atp and itt underlines the importance of evaluating itt-data providing a more realistic assessment of a treatment modality in practice. This treatment is especially recommended for patients with chronic type of AD, high compliance and time free for therapy.