Tumor necrosis factor-alpha enhances antitumor effects of radiation against glioma xenografts

Benzodiazepine discontinuation is characterized by a syndrome of increased activity and reduced seizure threshold that is similar to effects mediated by the glutamatergic system. To elucidate the involvement of the glutamatergic system in benzodiazepine tolerance and discontinuation, we administered lorazepam, the NMDA antagonist CPP, and the combination of these compounds either concomitantly or consecutively to mice via osmotic pumps and evaluated pentylenetetrazole-induced seizure threshold, open-field activity, and benzodiazepine receptor binding during and after chronic administration. Animals receiving lorazepam alone developed partial tolerance at 7 days and complete tolerance at 14 days to the anticonvulsant effects of lorazepam. This effect was partly attenuated by CPP coadministration with lorazepam. This combination produced only partial tolerance. A reduction in seizure threshold was observed 4 days after discontinuation of lorazepam alone. This effect was abolished by coadministration of CPP with lorazepam and by CPP administration during the withdrawal period. Benzodiazepine binding in most structures examined was significantly reduced at 14 days during chronic lorazepam administration (versus 1 day), and coadministration of CPP did not alter this decrement. After lorazepam discontinuation, binding was increased at 4 and 7 days versus chronically treated animals and versus vehicle within the cerebral cortex. This effect was abolished by coadministration of CPP as well as by CPP administration during the lorazepam withdrawal period. These data support the involvement of the glutamatergic system in benzodiazepine tolerance and discontinuation.     

Changes in blood flow velocity and diameter of the middle cerebral artery during hyperventilation: assessment with MR and transcranial Doppler sonography

PURPOSE: To compare blood flow velocity changes within the middle cerebral artery (MCA) during hyperventilation, as measured with by both transcranial Doppler sonography and MR imaging, with the diameter of the MCA as measured with MR imaging alone. METHODS: The studies were performed in six healthy volunteers ranging in age from 22 to 31 years (mean, 27 years). Transcranial Doppler sonography was carried out with a range-gated 2-MHz transducer. MR examinations were done on a 1.5-T imaging unit. MR angiography was performed using the time-of-flight technique. MR flow measurements were carried out by using the phase-mapping technique with an ECG-triggered phase-contrast sequence. RESULTS: During hyperventilation, the mean blood flow velocity of the proximal MCA declined by 49.6% +/- 5.7 (mean +/- standard deviation) as measured with Doppler sonography, and by 47% +/- 4.6 as measured with MR flow calculation. The diameter of the MCA (3.4 +/- 0.3 mm) remained unchanged on MR imaging studies (3.3 +/- 0.3 mm). CONCLUSION: We found a good correlation between relative flow velocity changes measured by transcranial Doppler sonography and MR techniques. MR imaging revealed no significant changes in the diameter of the proximal MCA during normal versus hyperventilation. Relative changes in flow velocity in the MCA would thereby reflect relative changes in cerebral blood flow, at least during hyperventilation.     

Metabolic consequences of alcohol dependency

Alcohol dependency leads to a variety of biochemical adaptations and morphological changes which may be considered as either adaptive or destructive. This ranges from the utilization of ethanol as a metabolic fuel, to overt tissue and cellular damage, and may lead to increases in morbidity and mortality. Virtually every organ system is affected by either acute and chronic ethanol exposure and numerous metabolic pathways are altered. As a consequence of these wide ranging effects, it is extremely difficult to cover every aspect of alcohol toxicity in a single review. Instead, attention is focussed on selected areas, such as nutrition and protein metabolism in the liver and bone (and to a lesser extent, skeletal muscle and the gastrointestinal tract). The aim is to illustrate the numerous ways in which alcohol affects the body.     

Family dissolution, family reconstitution, and children's educational careers: recent evidence for Sweden

Both longitudinal and cross-sectional analyses on a large and recent Swedish data set demonstrate that, compared to children in intact families, children who have experienced family dissolution or reconstitution show lower educational attainment at age 16. Time constraints do not seem to be an important mechanism behind the negative effect of separation. Economic deprivation affects children's attainment negatively, but downward social mobility appears to be an even more important causal mechanism: Losing the parent with the higher social position probably reduces social capital and aspirations. When we control for socioeconomic characteristics, a small net effect of separation and reconstitution remains.     

Localisation of insulin-like growth factor-I (IGF-I) immunoreactivity in the olivocerebellar system of developing and adult rats

The molecular mechanisms which underlie the development of the olivocerebellar topography are not fully understood. Insulin-like growth factor-I (IGF-I) is a growth factor known to play important roles in neural development and it has been identified within the cerebellum and the inferior olive. To assess the contribution of IGF-I to the development of climbing fibre topography, the distribution of IGF-I-like immunoreactivity (IGF-I IR) was identified in the cerebellar cortex and inferior olive of rats, 0, 3, 5, 7, 10, 15, 21, 28 and 90 days old. In the cerebellar cortex, IGF-I IR was localised solely to Purkinje cells and its distribution was spatially and temporally regulated in a manner which coincides with climbing fibre development. At birth, weak IGF-I IR was detected in a few Purkinje cells in the ventral vermis. More Purkinje cells became positive until at postnatal day 7(P7) all Purkinje cells displayed IGF-I IR. Subsequently, a subpopulation of Purkinje cells lost their reactivity for IGF-I to leave IGF-I-positive cells organised into sagittal bands by P15. IGF-I IR was also seen in all subdivisions of the inferior olive between birth and P10 in a distribution which paralleled the maturation of the inferior olive. The Purkinje cell and inferior olivary IGF-I IR parallels climbing fibre development and thus the results of this study support the hypothesis that IGF-I is involved in the development of climbing fibre topography.     

Ligation of the left renal vein in epm1-Wistar rats: functional and morphologic alterations in the kidneys, testes and suprarenal glands

OBJECTIVE: The ligation of the left renal vein (LLVR) in man is a controversial procedure in view of the risks of lesion to the renal parenchyma. With the objective of studying the morphologic and functional alterations caused by these lesions, we conducted experimental research with rats. MATERIAL AND METHODS: 64 male adult EPM1-WISTAR rats were used, divided into 8 groups-4 for LLRV and four for control. Each LLRV group and corresponding control group were sacrificed progressively on the 7th, 15th, 30th and 60th day after the initial surgery. RESULTS: We found morphofunctional alterations only in animals that underwent LLRV in the four periods of sacrifice. The proteinuria creatinine in serum, testosterone in serum and serum corticosterone in serum showed practically no alteration in relation to the normal values for rats. Statistically significant severe histological lesions were found in the kidneys and testes of the LLRV groups. Lesions in the suprarenal glands were also present in these groups, but no sufficient to demonstrate statistical significance. CONCLUSION: Based on these results we can conclude that the ligation of the left renal vein is a procedure of high risk in these animals.     

Influence of two weeks of non-weight bearing on rat soleus motoneurons and muscle fibers

OBJECTIVES: To analyse the ethical implications of informing patients about their do-not-resuscitate status (DNR). DESIGN: Questionnaire. SETTING: Nationwide, 6 months after the publication of guidelines on DNR in 1994. SUBJECTS: A 10% random sample of the members of the Swedish Cardiac Society. 104 physicians and 196 nurses. MAIN OUTCOME MEASURES: To what extent are patients, physicians and nurses involved in decisions about DNR, and how should the ethical conflict involved in informing patients about their DNR status be described and analysed? RESULTS: Of 73% responding, 84% of the physicians and 8% of the nurses had made a DNR decision. The decision was regarded as ethically right and well timed and it was discussed with 33% of the competent patients. Half of the respondents believed that DNR orders should be discussed with the competent patient. but still only one third of the patients are involved. The ethical conflict is analysed using the principles of autonomy and nonmaleficence as value premises. CONCLUSIONS: Many physicians are still reluctant to find out what the patient wants. Being ignorant they risk harming the patient. It is recommended that information about DNR status should be given incrementally and that the attitudes of the old and chronically ill in-hospital patients are studied. Do they want to be informed, and if so, how and when do they want it to be done?     

Chimeric bispecific OC/TR monoclonal antibody mediates lysis of tumor cells expressing the folate-binding protein (MOv18) and displays decreased immunogenicity in patients

The current environment in which medicine is taught and practiced requires that medical schools pay increased attention to the faculty member's roles, rewards, career development, and productivity. Medical schools must make strategic decisions about the allocation of resources that can nurture their faculties and support the activities in academic and community settings in which faculty are involved. From 1993 to 1995 Allegheny University of the Health Sciences (formerly Medical College of Pennsylvania and Hahnemann University) designed a comprehensive system for the professional development of faculty. This system is based upon expanded categories of faculty academic activity and scholarship. New programs were implemented to reorient faculty toward conducting and documenting the expanded array of scholarly activities. The main characteristics of the new system are the establishment of formally defined performance expectations, the vertical alignment of the individual faculty member's objectives with the department's mission and the school's mission, and an increasing emphasis upon faculty interdependence, accountability, and use of sound business practices. The authors describe these and other aspects of the design of the new system in detail and report initial results and lessons learned from the system's implementation, evaluation, and dissemination throughout the university. The long-term success of this comprehensive professional development program will be assessed over time by observing how this institution advances its mission in a well-planned and cost-effective manner that retains talented, productive, and professionally fulfilled faculty.