Biomedical subjects
Publications and source records attributed to E Baum.
Using (R)-propene oxide as a chiral building block a convergent enantioselective synthesis of the potent neuronal cell protecting alkaloid lavanduquinocin has been accomplished by the iron-mediated one-pot construction of the carbazole framework.
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A stereoselective synthesis of the disilyl derivatives 3 is achieved by the title reaction, an unprecedented Lewis acid promoted domino reaction, between the cross-conjugated dienone 1 and the allylsilanes 2. The configurations of the five stereogenic centers of this novel ring system are established in the first step of the reaction sequence, the double [3+2] cycloaddition.
OBJECTIVES: Rapid aid provided by lay witnesses and emergency services can improve the outcome in medical emergencies arising in the community. We attempted to study the quality of first aid rendered by lay persons, paramedical personnel, and community medical practitioners attending out-of-hospital emergencies. We also evaluated the frequency of first aid provided before the arrival of specialised emergency physicians. METHODS: Over a period of six months all emergencies in a rural district of Germany leading to the pre-hospital medical service being dispatched were studied. Specialised community emergency physicians arriving at the site of the event recorded demographic, clinical, and process data using a standardised instrument. They also assessed the performance of lay persons, paramedical personnel, and community physicians providing immediate care. Implicit and explicit criteria were used. RESULTS: In 97% of cases analysed (n = 1150) members of the above mentioned groups were present before the arrival of the dedicated medical service. Lay persons were judged to provide inadequate care especially with regard to airway management and immobilisation of suspected fractures. For paramedical personnel, the administration of medication, venous lines and immobilisation turned out to be problematic areas. Medical practitioners fell below the defined standards especially in airway management, immobilisation and venous lines. CONCLUSION: Our project has shown how important the evaluated groups are for community emergency care. Despite methodological problems in this area of study, the shortcomings demonstrated may be targeted by future training at different levels.
Persistent cognitive deficits are one of the most important sequelae of head injury in humans. In an effort to model some of the structural and neuropharmacological changes that occur in chronic postinjury brains, we examined the longitudinal effects of moderate vertical controlled cortical impact (CCI) on place learning and memory using the Morris water maze (MWM) test, morphology, and vesicular acetylcholine (ACh) transporter (VAChT) and muscarinic receptor subtype 2 (M2) immunohistochemistry. Vertical CCI (left parietal cortex, 4 m/sec, 2.5 mm; n = 10) or craniotomy (sham) was produced in male Sprague-Dawley rats (n = 10). Place learning was tested at 2 weeks, 4 weeks, 3 months, 6 months, and 12 months postinjury with the escape platform in a different maze quadrant for each time point. At each interval, rats received 5 days of water maze acquisition (latency to find hidden platform), a probe trial to measure place memory, and 2 days of visible platform trials to control for nonspecific deficits. At 3 weeks, half the animals were sacrificed for histology. At these injury parameters, CCI produced no significant differences in place learning between injured and sham rats at 2 weeks, 4 weeks, or 6 months after injury. However, at 3 and 12 months, the injured rats took significantly longer to find the hidden platform than the sham rats. Probe trial performance differed only at 12 months postinjury between injured (25.73+/-2.1%, standard error of the mean) and sham rats (44.09+/-7.0%, p < 0.05). The maze deficits at 1 year were not due to a worsening of performance, but may have resulted from a reduced ability of injured rats to benefit from previous water maze experience. Hemispheric loss of 30.4+/-5.5 mm3 was seen at 3 weeks after injury (versus respective sham). However, hemispheric loss almost doubled by 1 year after injury (51.5+/-8.5 mm3, p < 0.05 versus all other groups). Progressive tissue loss was also reflected by a three- to fourfold increase in ipsilateral ventricular volume between 3 weeks and 1 year after injury. At 1 year after injury, immunostaining for VAChT was dramatically increased in all sectors of the hippocampus and cortex after injury. Muscarinic receptor subtype 2 (M2) immunoreactivity was dramatically decreased in the ipsilateral hippocampus. This suggests a compensatory response of cholinergic neurons to increase the efficiency of ACh neurotransmission. Moderate CCI in rats produces subtle MWM performance deficits accompanied by persistent alteration in M2 and VAChT immunohistochemistry and progressive tissue atrophy. The inability of injured rats to benefit from repeated exposures to the MWM may represent a deficit in procedural memory that is independent of changes in hippocampal cholinergic systems.
Intercellular adhesion molecule-1 (ICAM-1) is an adhesion molecule of the immunoglobulin family expressed on endothelial cells that is upregulated in brain as part of the acute inflammatory response to traumatic brain injury (TBI). ICAM-1 mediates neurologic injury in experimental meningitis and stroke; however, its role in the pathogenesis of TBI is unknown. We hypothesized that mutant mice deficient in ICAM-1 (-/-) would have decreased neutrophil accumulation, diminished histologic injury, and improved functional neurologic outcome versus ICAM-1 +/+ wild type control mice after TBI. Anesthetized ICAM-1 -/- mice and wild-type controls were subjected to controlled cortical impact (CCI, 6 m/sec, 1.2 mm depth). Neutrophils in brain parenchyma and ICAM-1 on vascular endothelium were assessed by immunohistochemistry in cryostat brain sections from the center of the contusion 24 h after TBI (n = 4/group). Separate groups of wild-type and ICAM-1-deficient mice (n = 9-10/group) underwent motor (wire grip test, days 1-5) and cognitive (Morris water maze [MWM], days 14-20) testing. Lesion volume was determined by image analysis 21 days following TBI. Robust expression of ICAM-1 was readily detected in choroid plexus and cerebral endothelium at 24 h in ICAM-1 +/+ mice but not in ICAM-1 -/- mice. No differences between groups were observed in brain neutrophil accumulation (9.4 +/- 2.2 versus 11.1 +/- 3.0 per x100 field, -/- versus +/+), wire grip score, MWM latency, or lesion volume (7.24 +/- 0.63 versus 7.21 +/- 0.45 mm3, -/- versus +/+). These studies fail to support a role for ICAM-1 in the pathogenesis of TBI.
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The objective of the study is to examine whether medical care patterns and/or outcomes for patients under a prepaid system differ from those under fee-for-service according to social class. An effect of this kind was suggested by the investigators reporting on the RAND Health Insurance Experiment (RAND HIE). We performed a cross-sectional study in family practice in Germany (fee-for-service) and the UK (predominantly capitation i.e. prospective payment). 778 attending patients aged 18 and above were included. Indicators of care, relating mainly to cardiovascular prevention, were collected by patient interview and questionnaire, doctor's questionnaire, analysis of records, and blood pressure (BP) measurement. Multiple linear and logistic regression models with these indicators as dependent variables were calculated to examine possible interactions between social class and system of payment. Social class as a main effect was related to diastolic BP, BP measurement frequency, and the number of non-pharmacological interventions to lower BP. The data on the process and the outcome of primary care from British and German family practice do not show any significant interaction between system of family practitioners' remuneration and patients' social class. We were unable to reproduce the effect postulated by the RAND HIE investigators.
The effect of different systems of remuneration on preventive activity of family practitioners (FPs) were studied. Interventions against smoking were compared in FPs' practices in Germany and the UK. Almost 800 consecutively attending patients were included in a cross-sectional survey. Smoking prevalence was remarkably similar among German and British practice attenders. Slightly more than 50% of smokers in both countries remembered an intervention against their smoking by their FP or related staff. Multiple logistic regression analysis also showed that there was no significant difference for remembered interventions between the two countries (adjusted OR 1.15 [95%-Cl 0.6, 2.2]). The structure of interventions employed was similar in both countries. Most British and German ex-smokers denied that their FP had made an important contribution to their giving up smoking. There is evidence that, under capitation, FPs concentrate their activities on patients who are more at risk. Overall, however, the economic structure does not seem to influence the core of preventive behaviour of FPs to any great extent. Smoking cessation efforts in Family Practice need to be improved in both countries.
BACKGROUND: Fifty-seven children with acute lymphoblastic leukemia (ALL) receiving therapy who experienced overt isolated testicular relapse while in bone marrow remission were entered into a study that featured an intensive retreatment regimen. METHODS: The objective was to determine whether a change in chemotherapy and local irradiation would prevent subsequent marrow relapse and increase the survival rate. The regimens used (modified Berlin-Frankfurt-Munster or modified New York) delivered acceptable therapy based on analyses of toxicity data. RESULTS: Overall survival at 5 years from the time of testicular relapse was 47%, with an event-free survival of 43%. Events have been documented in 28 of 55 evaluable children. Analysis of these patients revealed that 23 children had bone marrow relapse, 4 children had central nervous system relapse, and 1 child had testicular relapse. In addition, two patients were removed from the study for toxicity, one child for infection (mucormycosis), and five children had a bone marrow transplantation while in remission and became ineligible to continue in the study. Two children were removed at the request of their parents, and nine children were lost to follow-up. CONCLUSION: Because of their high risk of developing systemic relapse, boys with ALL who experience isolated overt testicular relapse during active therapy should be retreated with intensive treatment.
In general practice many diagnostic labels are used that are related to cultural background rather than a scientific basis. To estimate the use of diagnoses like 'hypotension' and depression, a cross-sectional survey in German and British GPs' surgeries was performed. Prevalence of related symptoms, sociodemographic and medical data were recorded as well as actual and previous blood pressure levels. In German general practice, where 'hypotension' is an established entity, 17% of all patients attending were reported as hypotensive either by their doctor or by themselves. The proportion was twice as high among women than among men. It was more common among the young. One-quarter of these patients were on medication to raise their blood pressure. Actual and previous blood pressure levels failed to explain the occurrence of symptoms like tiredness, dizziness, headache etc. Demographic characteristics of patients diagnosed as depressed were similar in both countries. Presumably for economic reasons there is a tendency for German GPs to use more diagnostic labels of any kind. It was concluded that diagnostic labels attached to vague but frequently presented symptoms vary considerably between countries. They often lack a physiologic rationale. Nevertheless they often support the tendency to somatize common problems.
An escalating-dose trial of idarubicin, used weekly for 3 doses in combination with vincristine, prednisone, and L-asparaginase (VPLI), to reinduce remission of childhood ALL at first bone marrow relapse was conducted by the Childrens Cancer Study Group (CCSG). The maximum tolerated dose (MTD) of idarubicin, used in the manner, was determined to be 12.5 mg/m2/dose. Twelve of 16 (75%) evaluable patients in first marrow relapse of ALL treated at a dose of 10 or 12.5 mg/m2 entered a second complete remission, compared to 41 of 69 evaluable patients (59%) treated in a comparable way with daunorubicin (30 mg/m2) (VPLD). Prolonged myelosuppression was observed in both groups, but the frequency of documented bacterial sepsis and the duration of required hospitalization were greater among patients treated with idarubicin. No additional toxicity, specifically attributable to idarubicin, was observed at these doses.
Glucose metabolism of human leukemic cell lines CEM-C7 and CEM-C1 was investigated in vivo by 13C NMR using 13C-labeled glucose. Exact knowledge of glucose concentration, cell count, and cell viability of the cell suspensions made it possible to analyze glucose metabolism in detail. In both cell lines aerobic glycolysis accounts for virtually all glucose consumption. The use of D-[13C2]glucose provided a simple method to measure the glucose flux through the pentose phosphate pathway as 9% (CEM-C1) and 11% (CEM-C7) of glucose channeled into glycolysis. The dexamethasone-sensitive CEM-C7 cells consume glucose at a rate about 50% higher than the dexamethasone-resistant CEM-C1 cells. It is shown that this higher consumption correlates with a larger size of the CEM-C7 cells. Therefore in CEM cells the development of drug resistance does not seem to involve related changes in cell energetics.
31P Nuclear magnetic resonance spectra of perchloric acid extracts from wild-type human leukemic CEM-C7 cells and the dexamethasone-resistant CEM-C1 mutant reveal significant differences in concentrations of phospholipid precursors and ATP+, which indicate metabolic differences between these two cell lines. At high cell concentrations the CEM-C7 cells are growth inhibited, which is reflected by low phospholipid precursor levels, indicative of low phospholipid turnover. The CEM-C1 mutant does not exhibit this growth inhibition and has constant phospholipid precursor levels over the same cell concentration range. Dexamethasone causes phospholipid precursor and ATP levels in CEM-C7 to drop after 48 h, but spectra obtained for CEM-C1 cells continue to show high cell viability up to 72 h.
57 women were studied who were GMP patients, whose spontaneous menopause had occurred 6 to 36 months ago and who did not take any sexual hormones. Purpose of the study was to determine psychosocial influences on the time of onset of the menopause and on climacteric complaints. It was found that the overall impairment by hot flushes and pain in the limbs during this phase of life was largely independent of the studied parameters. With regard to the time of onset of the menopause there was a trend to an linear relationship between the factor "social dependence" and the age at which menopause occurred, as well as a link between that age and period intervals 5 years before cessation of menstrual bleeding. An enhanced tendency to exhaustion representing a nonspecific menopause syndrome was found particularly often in women who were highly "socially dependent". There was no relationship between climacteric complaints on the one hand and, on the other hand, experiences of loss, social stress and relief factors, partnership relations, experiences of menarche, menstruation and menopause as well as basic feeling tone; however, a depressive tone, as defined by the Giessen test, was clearly predominant in the examined population. It is concluded from these results that flushes in the early postmenopausal phase are mostly a biological phenomenon, whereas vegetative concomitant complaints are markedly dependent on psychosocial factors that correspond to a typically "feminine" role enactment as postulated by social convention.
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