Ichthyosen: Pathophysiologische Modelle der epidermalen Differenzierung

Zusammenfassung: Die Ichthyosen sind eine durch Schuppung oder Keratosen charakterisierte heterogene Krankheitsgruppe monogenetisch vererbter Verhornungsstörungen. In der Vergangenheit wurden sie aufgrund klinischer Zeichen und des Vererbungsmusters nosologisch eingeteilt. Als Folge des massiven Wissenssprunges im Gebiet der molekularen Genetik wurden nun zahlreiche Gendefekte im Gebiet der Ichthyosen aufgeklärt. Dadurch trat die Komplexität der Ichthyosen zutage, wobei ähnliche oder gleiche Phänotypen durch Mutationen in verschiedenen Genen verursacht werden können, währenddessen umgekehrt einzelne Gene in verschiedenen, zum Teil stark divergierenden Phänotypen resultieren können. Daher wurde eine neue Klassifizierung notwendig, die klinische und neue molekulargenetische Erkenntnisse berücksichtigt und vereint. In dieser Publikation folgen wir größtenteils der Einteilung, die anlässlich der ersten Ichthyosis Consensus Conference in Sorèze, Frankreich, festgelegt wurd

Comparative in-vitro activity of fleroxacin and other 6-fluoroquinolones against mycobacteria

The susceptibility of 11 clinical isolates of Mycobacterium tuberculosis, 3 M. kansasii,3 M. xenopi, 2 M.scrofulaceum, 2 M. marinum, 2 M. malmoense to fleroxacin,ciprofloxacin, norfloxacin, rifampicin, isoniazid, ethambutol, and streptomycin was determined by the standard proportion method (Middlebrook 7HlO agar). All M.tuberculosis,M. kansasii, M. xenopi,M. scrofulaceum, M. marinum,and M. malmoense isolates including those resistant to conventional antimycobacterials were inhibited by 0·5 mg/l of fleroxacin and ciprofloxacin, the lowest tested concentration. Fleroxacin and ciprofloxacin along with ofloxacin,pefloxacin, ansamycin, clofazimine and cycloserine were also tested against 14 isolates of the M. avium complex. Nine of 14 strains (64%) of the M. avium complex were found susceptible to 4 mg/l of fleroxacin and a similar percentage to the other quinolones. On the basis of its in-vitro potency and its favourable pharmacokinetic properties fleroxacin appears to be sufficiently active to warrantfurther experimental trials against difficult to treat mycobacteri

Treating Homeless Opioid Dependent Patients with Buprenorphine in an Office-Based Setting

CONTEXT Although office-based opioid treatment with buprenorphine (OBOT-B) has been successfully implemented in primary care settings in the US, its use has not been reported in homeless patients. OBJECTIVE To characterize the feasibility of OBOT-B in homeless relative to housed patients. DESIGN A retrospective record review examining treatment failure, drug use, utilization of substance abuse treatment services, and intensity of clinical support by a nurse care manager (NCM) among homeless and housed patients in an OBOT-B program between August 2003 and October 2004. Treatment failure was defined as elopement before completing medication induction, discharge after medication induction due to ongoing drug use with concurrent nonadherence with intensified treatment, or discharge due to disruptive behavior. RESULTS Of 44 homeless and 41 housed patients enrolled over 12 months, homeless patients were more likely to be older, nonwhite, unemployed, infected with HIV and hepatitis C, and report a psychiatric illness. Homeless patients had fewer social supports and more chronic substance abuse histories with a 3- to 6-fold greater number of years of drug use, number of detoxification attempts and percentage with a history of methadone maintenance treatment. The proportion of subjects with treatment failure for the homeless (21%) and housed (22%) did not differ (P=.94). At 12 months, both groups had similar proportions with illicit opioid use [Odds ratio (OR), 0.9 (95% CI, 0.5–1.7) P=.8], utilization of counseling (homeless, 46%; housed, 49%; P=.95), and participation in mutual-help groups (homeless, 25%; housed, 29%; P=.96). At 12 months, 36% of the homeless group was no longer homeless. During the first month of treatment, homeless patients required more clinical support from the NCM than housed patients. CONCLUSIONS Despite homeless opioid dependent patients' social instability, greater comorbidities, and more chronic drug use, office-based opioid treatment with buprenorphine was effectively implemented in this population comparable to outcomes in housed patients with respect to treatment failure, illicit opioid use, and utilization of substance abuse treatment

Late-Onset Multiple Self-Healing Squamous Epithelioma Ferguson-Smith Recurrence Induced by Radiotherapy.

We report the case of a woman in her 60s with confirmed multiple self-healing squamous epitheliomas (MSSE) Ferguson-Smith. After recurrences following surgery and radiotherapy, the patient was successfully treated with minimal surgical intervention combined with intralesional injections of triamcinolone acetate. The histological comparison between mature and regressed keratoacanthomas (KA) revealed an increased inflammatory infiltrate with numerous plasmacytoid dendritic cells in the regressed KA in comparison to the mature one, speaking in favor of an inflammation-mediated regression process. Corticosteroids injection in MSSE may have paradoxical effects with action on the proliferation phase rather than the inflammatory regression phase of the KA. Our case confirms previous reports showing that radiotherapy may exacerbate MSSE and should be avoided. Intralesional triamcinolone acetate injection is a safe and easy to use method also effective for multiple lesions. Our case underlines the difference between squamous cell carcinoma and KA, responding differently to therapies like imiquimod or radiotherapy

The validity of clinical diagnoses of dementia in a group of consecutively autopsied memory clinic patients

Background: Epidemiological studies show that up to 10 % of individuals aged 65 years and older suffer from dementia, most commonly from dementia of the Alzheimer Type (DAT) [1]. Clinicopathological studies are critical to our understanding of this disease and improving the accuracy of clinical diagnoses.Objectives: Our objectives were to examine the validity of clinical diagnoses of DAT, to determine the prevalence of different forms of dementia in this sample, and to investigate the relationship between age at death and polymorbidity.Subjects and method: Clinical data were available from 221 patients who had been examined at the Basel Memory Clinic between 1986 and 1996. From this population, 34 % (75 patients) were autopsied in the Department of Pathology, University Hospital Basel, and neuropathological examinations were additionally performed on 62 (83 %) of these patients. Clinical and neuropathological data were retrospectively compared.Results: 67.8 % of the neuropathologically examined patients received a definitive diagnosis of AD (Alzheimer's disease), vascular dementia (VaD) or mixed dementia (AD and VaD). AD alone or with other histopathological hallmarks of dementia was the most prevalent neuropathological diagnosis (63 %). VaD was deemed the only cause of dementia in only 4.8 % of patients. The sensitivity for DAT was 75.9 %, the specificity 60.6 %. Increasing age was associated with an increasing number of clinical and neuropathological diagnoses.Conclusion: The sensitivity and specificity of the clinical diagnoses of DAT found in our study are similar to previous reports (2-5). Older patients had more etiologies of their dementia than younger patients. This study reaffirms the need for internationally accepted criteria for clinical and neuropathological diagnoses, as well as further clinical-neuropathological investigations to further refine the clinical diagnostic proces

Dynamics of modal power distribution in a multimode semiconductor laser with optical feedback

The dynamics of power distribution between longitudinal modes of a multimode semiconductor laser subjected to external optical feedback is experimentally analyzed in the low-frequency fluctuation regime. Power dropouts in the total light intensity are invariably accompanied by sudden activations of several longitudinal modes. These activations are seen not to be simultaneous to the dropouts, but to occur after them. The phenomenon is statistically analysed in a systematic way, and the corresponding delay is estimated.Comment: 3 pages, 4 figures, revte

TRAIP is a regulator of the spindle assembly checkpoint.

Accurate chromosome segregation during mitosis is temporally and spatially coordinated by fidelity-monitoring checkpoint systems. Deficiencies in these checkpoint systems can lead to chromosome segregation errors and aneuploidy, and promote tumorigenesis. Here, we report that the TRAF-interacting protein (TRAIP), a ubiquitously expressed nucleolar E3 ubiquitin ligase important for cellular proliferation, is localized close to mitotic chromosomes. Its knockdown in HeLa cells by RNA interference (RNAi) decreased the time of early mitosis progression from nuclear envelope breakdown (NEB) to anaphase onset and increased the percentages of chromosome alignment defects in metaphase and lagging chromosomes in anaphase compared with those of control cells. The decrease in progression time was corrected by the expression of wild-type but not a ubiquitin-ligase-deficient form of TRAIP. TRAIP-depleted cells bypassed taxol-induced mitotic arrest and displayed significantly reduced kinetochore levels of MAD2 (also known as MAD2L1) but not of other spindle checkpoint proteins in the presence of nocodazole. These results imply that TRAIP regulates the spindle assembly checkpoint, MAD2 abundance at kinetochores and the accurate cellular distribution of chromosomes. The TRAIP ubiquitin ligase activity is functionally required for the spindle assembly checkpoint control