Differential involvement of protein 4.1 family members DAL-1 and NF2 in intracranial and intraspinal ependymomas.

Ependymomas are malignant CNS neoplasms with highly variable biologic behavior, including a generally better prognosis for intraspinal tumors. Inactivation of the NF2 gene on 22q12 and loss of its protein product, merlin, have been well documented in subsets of meningiomas and ependymomas. DAL-1, a related tumor suppressor and protein 4.1 family member on 18p11.3, has also been recently implicated in meningioma pathogenesis, though its role in ependymoma remains unknown. Therefore, we evaluated 27 ependymomas (12 intracranial and 15 spinal) using fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) to determine NF2/merlin and DAL-1/DAL-1 status at the DNA and protein levels. Demonstrable NF2 and DAL-1 gene deletions were each detected in 6 (22%) ependymomas. All 5 merlin losses by IHC occurred in spinal ependymomas (P =.047), whereas 5 (71%) DAL-1-negative cases were intracranial (P =.185). The former result is consistent with prior observations that NF2 mutations are generally limited to spinal ependymomas. In contrast to meningiomas, simultaneous merlin and DAL-1 losses were not encountered. Our findings suggest that (1) NF2 and DAL-1 losses are involved in the pathogenesis of spinal and intracranial ependymoma subsets, respectively and (2) given the number of cases with no demonstrable losses, other cellular perturbations must also be critical for tumori-genesis.     

Synthesis and NMR-analysis of deuterated and tritiated cyclooctyl acetic acid

To increase the bio-availability of naturally occurring steroids, esterification of the 17-hydroxy position is a useful approach. Besides (branched) alkanecarboxylic acids¹) and cyclohexanecarboxylic acid²) also cyclooctyl acetic acid ( 1 ) was applied. To establish the biological fate of the cyclooctyl acetic acid part of steroids the tritiated molecule was synthesized (Figure 1). Cyclooctanone ( 3 ) was condensed with cyanoacetic acid³) and the resulting cyanide ( 4 ) was hydrolyzed to cyclooctenyl acetic acid ( 2a )⁴) which contained according to ¹H NMR and ¹³C NMR 20% of the isomeric 2b (¹H NMR (C²HCl₃): 5,58 ppm (t, CH of 2a ) and 5,63 ppm (br.s CH of 2b ) ¹³C NMR(C²HCl₃): 129,6 ppm (CH of 2a ) and 115,0 ppm (CH of 2b )).     

Ökonomisches Rehabilitations-management bei chronischen Rückenschmerzen

BACKGROUND AND STUDY PURPOSE: Back pain causes high costs to society. In Germany, these amount to an estimated total of 5 billion euro of direct costs per year and 13 billion euro of indirect costs, the latter being caused by incapacity to work. The purpose of this study is to develop a concept for economic rehabilitation management. This concept is based on the managed care approach and aims at improving efficiency of care. METHODS: The concept development consists of a theoretical and an empirical part. The method of the theoretical part is based on a systematic literature review on managed care (not included in this article), health systems research and the analysis of economic incentives. For the empirical investigation, long term effects and costs were calculated. For the evaluation of effects, we psychometrically tested and used the EuroQol (EQ-5D) as a measure of health-related quality of life (HRQL). The calculation of costs (both direct and indirect) is based on routine data of payers, a cost diary and the internal cost accounting systems of rehabilitation clinics. We statistically analysed the cost distribution and identified predictors of the management targets (e.g., costs of care) by means of regression analyses. RESULTS: The market-driven managed care approach is based on three tools: (1) a primary care system with case management and gatekeeping, (2) direct influence on providers by utilisation review and setting guidelines, and (3) indirect influence by setting supply-side economic incentives via the remuneration mode. The third managed care tool is most important when managing the rehabilitation of working age patients with chronic low back pain from an economic point of view. This concept consists of three components: (1) a case-based budget for direct costs; this is a prospective remuneration mode for an integrated primary care network including a rehabilitation facility, (2) retrospective bonus payments which are related to savings of indirect costs, and (3) retrospective bonus payments which are related to the effectiveness of rehabilitation, i.e. gains in HRQL. Common features of the three management components are a long-term perspective (e.g., from admission to a rehabilitation clinic until six months after discharge) and risk-adjustment of the three management targets (i.e., direct and indirect costs and gains in HRQL) in order to avoid selection and to limit the financial risk for providers. The EuroQol instrument shows acceptable psychometric properties in the rehabilitation setting for back pain patients. This instrument may yield two kinds of preference-based index values, one reflecting the preferences of the general population and one those of the patient. The Pearson correlation of these two approaches is fair, but there is a systematic difference. Empirical investigation shows that the distribution of both direct and indirect costs is skewed to the right. Statistically relevant predictors of the management targets are incapacity to work and HRQL at admission. CONCLUSIONS: Economic rehabilitation management might help to save money and to improve health outcomes, thus increasing the efficiency of care. The results of our empirical studies show the feasibility of tools for the economic management of rehabilitation. Risk adjustment of the management components is of paramount importance.     

Norepinephrine applied in the paraventricular hypothalamic nucleus stimulates vasopressin release

The present experiments were designed to investigate the effect of norepinephrine (NE) applied directly in the area of the paraventricular nucleus (PVN) of the hypothalamus on arginine-vasopressin (AVP) release and blood pressure. A microinjection of 0.4 micrograms NE in the PNV produced a plasma AVP level of 26.3 +/- 5.3 pg/ml compared to 5.3 +/- 0.6 pg/ml in controls receiving dextrose (P less than 0.001). This rise was associated with blood pressure elevations varying between 10 and 13 mm Hg, lasting for about 5 min. Systemic injection of an antivasopressor AVP antagonist reversed or prevented the blood pressure rise induced by NE microinjection. The data suggest that locally applied NE in vasopressinergic neurons of the hypothalamus stimulates the release of AVP and induces an AVP-dependent rise in blood pressure.     

Differences in oral health status between institutionalized and non-institutionalized older adults

Differences in oral health status between independent and institutionalized adults have been difficult to interpret because the latter population is typically older and has a higher proportion of women, confounding any association between institutionalization and disease levels. We undertook an analysis of oral disease amongst institutionalized (n = 149) and non-institutionalized (n = 246) samples of older adults randomly selected from the population in East York, Ontario. When the confounding effects of age and gender were controlled by constructing 67 matched pairs, institutionalized people were more than twice as likely to be edentulous (OR = 2.17, 95% CI = 1.09-4.29). This association was confirmed using data from all subjects in a logistic regression model. Analysis of covariance of data from dentate subjects revealed that the institutionalized seniors had fewer filled teeth (P less than 0.05, controlling for age and sex), but there were no statistically significant differences in the number of teeth which were missing, decayed, or requiring extraction. These findings suggest that antecedent, sociodemographic factors prior to institutionalization are responsible for the higher probability of oral disease in this group of older adults.     

Zur Frage der osmotischen Erythrocytenresistenz bei Nervösen und Psychisch-Kranken

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