[On the introduction of the new study plan for the pharmaceutical worker].
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Education, Pharmacy↗
Biomedical subjects
C Becker
Publications and source records attributed to C Becker.
[Contribution to the vasculo-ossal dysembryoplasia Klippel-Tréaunay with agenesis of the deep veins].
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Adult↗
[Studies on the possibility of influencing the respiration center by x-irradiation].
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Adult↗
MLV-10A1 retrovirus pseudotype efficiently transduces primary human CD4+ T lymphocytes.
BACKGROUND: Previously, we showed that retroviral vectors pseudotyped with the envelope of the amphotropic murine leukemia virus 10A1 (MLV-10A1) more efficiently transduce primary human CD8+ T lymphocytes when compared with other A-MLV, gibbon ape leukemia virus (GaLV) and feline endogenous retrovirus (RD114) vector pseudotypes. For the success of several gene therapeutic approaches (ADA, HIV) it is important to effectively transduce primary human CD4+ T lymphocytes. METHODS: We have used retroviral vectors encoding the enhanced green fluorescent protein (EGFP) as a marker gene and carrying envelopes of MLV-10A1, A-MLV and GaLV and have analyzed the transduction efficiency of both human CD4+ T cell lines (CEM, H9, HUT78, J16) and primary human CD4+ T lymphocytes using a RetroNectin-assisted transduction protocol and virus-containing supernatant. RESULTS: In CD4+ T cell lines the MLV-10A1 vector pseudotype was most effective and infected up to 85% of cells which then stably expressed GFP over time. MLV-10A1 was also superior and infected approximately 32% of primary human CD4+ T lymphocytes in comparison to GaLV (18%) and A-MLV (12%). The superior efficiency of MLV-10A1 for the transduction of CD4+ T cells correlates with the longer half-life of this pseudotype in comparison to A-MLV and, as previously shown by interference analysis, with the usage of both the A-MLV (Pit2) and the GaLV receptor (Pitl) for cell entry. CONCLUSIONS: MLV-10A1 is a suitable vector for transferring genes with high efficacy into primary human CD4+ T lymphocytes. The use of MLV-10A1 pseudotyped vectors should make it easier to obtain a sufficient number of gene-modified T lymphocytes for an adoptive transfer.
Animals↗
CIRSE '96 summary report. Proceedings of the Annual Meeting of CIRSE. Madeira, Funchal, September 8-12, 1996.
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Humans↗
Therapy of metastatic breast cancer with humanized antibodies against the HER2 receptor protein.
The HER2 protein, a member of the epidermal growth factor family, is encoded by the protooncogene c-erbB-2. Its overexpression, occurring in approximately one-third of all breast carcinomas, is associated with a poor prognosis. A humanized mouse antibody against HER2 has been developed by genetic engineering. Here an unspecific human IgG was connected to the recognizing mouse IgG fragment. The allergization typical for allogeneic antibodies does not take place in this context. The effectiveness of this antibody has been confirmed by two international prospective phase III trials that tested it alone and combined with chemotherapy. Both modes of application increased the response rates and the time to progression. Side-effects were rare except for a high rate of cardiac dysfunction when the antibody was combined with anthracyclines. The effectiveness and negligible side-effects of the chimeric antibody against HER2 (Herceptin) render it a valuable tool in the treatment of breast cancer.
Antibodies, Monoclonal↗
Pharmacokinetics of nimodipine in multimorbid elderly patients with chronic brain failure.
Twenty-one elderly patients with chronic brain failure received a single 30 mg oral dose of the calcium channel blocker nimodipine followed by two weeks of 30 mg three times a day (t.i.d.) administration. The aim of this study was to assess if drug accumulation occurred in our frail elderly subjects under this dose regimen. Plasma concentrations of nimodipine and three main metabolites were determined by gas chromatography. During the 2-week period we did not find significant changes in peak plasma concentrations and corresponding areas under the plasma concentration-time curves. Trough nimodipine plasma concentrations before administration of the morning dose were similar on days 7 and 14. Therefore, no evidence of drug accumulation was found. Blood pressure and heart rate remained stable throughout the study period and no adverse effects were observed. During the study period, there was a decline in the proportion of patients who complained about dizziness and insomnia. Overall, our data suggest that there is no need to alter the usual adult dose of nimodipine if this drug is administered to multimorbid frail elderly patients suffering from chronic brain failure.
Journal Article↗
Transcoronary sinus administration of autologous bone marrow in patients with chronic refractory stable angina Phase 1.
PURPOSE: Based on our preclinic studies with autologous unfractionated bone marrow (AUBM) via coronary sinus with transitory occlusion, a clinic study in patients with chronic stable angina was designed. The objectives were to evaluate safety, tolerance and feasibility. METHODS AND MATERIALS: A multicenter prospective study with inclusion and exclusion criteria defined by an Independent Clinical Committee was carried out. Fourteen patients underwent transcoronary sinus administration of freshly aspirated and filtered AUBM (60-120 ml). Safety and tolerance were evaluated. Feasibility was evaluated with Seattle Angina Questionnaire (SAQ), Canadian Cardiovascular Society (CCS) angina classification (baseline-Day 180), myocardial perfusion (baseline-Day 90) with independent core laboratory and coronary angiography (baseline and Day 30). RESULTS: There were no changes in the safety and tolerance parameters. Preliminary clinical efficacy at Day 180 disclosed a significant improvement of 38%, evaluated by the SAQ. The CCS angina classification shows that the mean angina class was 3.0+/-0.55 at baseline and improved to 2.0+/-0.00 at Day 180 (P <.001). Semiquantitative radionuclide perfusion imaging (core lab) showed a significant improvement at Day 90 in 13/14 patients, with a mean improvement of 24% at rest (P <.01) and 33% at stress (P <.05). Coronary angiography showed more collateral vessels in 9/14 patients. CONCLUSIONS: We can conclude that AUBM via coronary sinus with transitory occlusion is tolerable and safe. Significant improvement in the myocardial perfusion at Day 90 and in the quality of life at Day 180 was observed.
Angina Pectoris↗
[Change in the CCD angle and the femoral anteversion angle by hip prosthesis implantation].
PURPOSE: The aim of the present study was to measure and interpret the change of the collodiaphyseal (CCD) angle and femoral anteversion after total hip replacement. METHODS: We prospectively examined 52 patients with coxarthrosis, who were treated by total hip replacement. Preoperatively and postoperatively we used a standard X-ray ap view to measure the CCD angle and computerized tomography to determine the femoral anteversion. These projected angles were converted into the real angles by using the method of König and Schult. RESULTS: On average the preoperative real CCD angle was 128 degrees (+/- 8.9 degrees) and the postoperative angle 145 degrees (+/- 4.8 degrees), preoperatively the real femoral anteversion angle was 14.1 degrees (+/- 6.9 degrees) and postoperatively 10.8 degrees (+/- 6.2 degrees). CONCLUSIONS: The effect of the postoperative valgisation can be explained by the given CCD angle of the used femoral stem prosthesis of 140 degrees (cemented Weller II stem) and 145 degrees (cementless CLS classic stem). It is possible that due to the valgisation and the decreased offset of the femoral stem prosthesis compared to the preoperative conditions the gluteal muscles are insufficient and overloaded. It is also known that the change of the femoral anteversion from the physiological conditions causes an increase of the torsional moment. The resulting increased interface load could possibly be a reason for loosening of the femoral stem. The conclusion can be drawn that the CCD angle and the femoral anteversion should more carefully be considered by the surgeon in total hip replacement. This could be reached by an exact implantation technique and the choice of the appropriate stem prosthesis with different CCD angles.
Adult↗
[Epidemiology of accidental falls in the elderly].
INTRODUCTION: There is a lack of epidemiological data on falls and fall-related injuries for the aged population in Germany. The purpose of the article is to present the available data focusing on the incidence of the fracture types that carry the highest risk for mortality, hospitalization and persisting disabilities. METHODS: The paper reports on a 10% representative sample that was drawn by the Federal Bureau of Statistics. A medline search for 1980-1998 was performed to identify relevant articles. The OECD database was used for mortality rates after injurious falls. If no sufficient data were published for Germany, incidence rates of demographic comparable European regions are reported. RESULTS: The number of fractures of the lower extremity (ICD 820-829) followed by hospitalization was 139,000 in 1996 for elderly (65+ years). Fractures of the upper extremities (ICD 810-819) requiring hospitalisation were reported for 65,000 persons aged 65+ years and head trauma (ICD 850-851) followed by hospitalization in this age group for 29,000 persons. There remains an information gap on the incidence of falls and fall-related sequelae without hospitalization in Germany. CONSEQUENCES: Facing, the demographic transgression the prevention of falls and fall-related injuries gains a high priority. Operative management and rehabilitation procedures for elderly trauma patients should be further evaluated and improved.
Accidental Falls↗
[Therapy of para-articular hip fractures in the elderly].
UNLABELLED: Fractures of the hip in old patients are life-threatening events. A steady increase of that fracture type is likely in the near future. Surgical therapies and strategies have to consider the special requirements and problems of geriatric patients to achieve better results. They have to be designed together with new concepts of geriatric rehabilitation programmes. MATERIAL AND METHODS: In 1992 148 patients with hip fractures were treated at the department of traumatology, University Ulm. Follow-up parameters were daily activities in life pre- and postoperatively as well as mortality, type of fracture and surgical treatment. RESULTS: There were 79 femur fractures of the collum and 69 fractures of the trochanteric region. Mean age was at 81.2 and 81.9 years respectively (68 f/11 m versus 52 f/13 m). At the time point of accident 84 patients lived at home whereas the remaining stayed at a nursing home. The highest mortality was found in patients living in a nursing home (93%). The overall mortality one year following the trauma was 26%. 50% of the patients had hip prosthetic replacement, the remaining received a gliding screw, 9 patients a proximal femoral nail or lag screws (n = 6). CONCLUSION: Our results demonstrate that hip fractures in geriatric patients have a high mortality, especially in those living in a nursing home. The surgical concepts should aim to reduce that number and to allow the same daily activity of life as preoperatively. The main part in these concepts is an early start of geriatric rehabilitation. There are at least two groups. On the one hand, the active old patient who acquires his fracture during an activity. In this cases the aim must be the full rehabilitation and afterwards returning to normal environment. On the other hand there are the patients living in a nursing home who have the highest risk of injury related death. In these patients the first aim must be prevention of the accident.
Aged↗
[Reperfusion capacity of the femur head after ischemia--an experimental study].
PURPOSE OF THE STUDY: The aim of this study was to evaluate bone blood flow of the proximal femur during experimentally induced ischemia and to document the ability of epiphyseal and metaphyseal reperfusion. METHODS: 11 pigs (danish landrace) were used to investigate the effect of tamponade by increased joint pressure (Dextran 70) on the perfusion of the femoral head. Additional 8 pigs were used as control. The blood flow in the hip joint was studied by means of the microsphere technique. The flow was determined before, during and after intraarticular pressure increase. With the "radioactive tracer microsphere"-method the blood flow of the epiphysis, metaphysis and proximal femoral corticalis could be measured. RESULTS: In the epiphyseal femoral head the initial blood flow rate, 11.7 ml/min/100 g, was not significant different from that of the control side (11.1 ml/min/100 g). The blood flow decreased in the ischemic phase to 1.8 ml/min/100 g followed by reperfusion to 13.5 ml/min/100 g (p < 0.01). The bone blood flow of reperfusion was not significant different from that of the initial blood flow rate but in 2 cases a "blow out" of the epiphyseal bone blood flow was seen. The proximal femoral metaphysis showed the highest of the measured intraosseous flow rates (17.9 resp. 23.3 ml/min/100 g). During ischemia and reperfusion of the epiphysis bone blood flow of the metaphysis remained the same. The proximal femoral corticalis showed the lowest of the measured intraosseous flow rates. The operated (10.1 ml/min/100 g) and contralateral hip side (11.7 ml/min/100 g) showed no significant differences in the initial blood flow rate. During ischemia and reperfusion the blood flow of the proximal corticalis showed no significant difference to the initial blood flow corresponding to the metaphysis. CONCLUSIONS: Our study demonstrates disturbances of the circulation of different regions of the femoral head during intraarticular pressure increase and following pressure decrease of the growing pig. 2 "blow outs" document a vulnerable proximal epiphysis already after a 6-hour ischemia. Additional minor "bone quality" in cases of certain diseases (kidney transplantation, leukemia) and special administration of drugs (corticosteroids) seem to create an additional vulnerability of the proximal femoral head. The experiment proves to be a reliable model for decreasing the blood flow of the growing epiphysis temporarily and to document the beginning of normal reperfusion. With this model it is possible to examine the vulnerability of the epiphyseal perfusion after different diseases and under the influence of different medication.
Animals↗
[Effect of bradykinin on pressure changes in the femur head epiphysis--an experimental and magnetic resonance tomography study].
AIM OF THE STUDY: The aim of this study was to evaluate the response of the femoral head to intraosseous pressure increases and to document blood flow of periarticular soft tissue after infusion of vasoactive substances. Beside that the value and imagery of native MRI after induced intraosseous pressure increase should be estimated for early detection of femoral head necrosis. METHODS: The alteration of intraosseous pressure and peripheral blood flow of the femoral head of beagle dogs was examined after administration of bradykinin as a vasoactive substance followed by subsequent magnetic resonance imaging (MRI). Bradykinin was injected into the arteriae circumflexae femoris lateralis and medialis of six beagle dogs. The administrations were made using a standard protocol with simultaneous measurement of venous blood flow and intraosseous pressure distribution in the epiphysis of the femoral head. Bradykinin was applied in regular time intervals followed by MRI. RESULTS: At a mean epiphyseal pressure 14.66 mmHg (sigma: 2.42) in the femoral head, a mean flow of 91.6 ml/min (sigma: 16.08) was measured in the vena femoralis. After an administration of a defined concentration of bradykinin an increased epiphyseal pressure was recorded in the measured area. An average increase blood flow of the vena femoralis was observed at the beginning of the bradykinin-injection, followed by a circulatory volume reduction. The post-experimental MRIs showed massive oedema in the femoral musculature after bradykinin-application, however without osseous signal alterations in T1- or STIR-weighted images. CONCLUSION AND CLINICAL RELEVANCE: Our results indicate that acute intraosseous pressure increases are not accompanied by signal alterations in MRI. Obviously more extensive pressure induced lesions are necessary for detectable signal alterations, as these have already been demonstrated in patients with diagnosed femoral head necrosis.
Animals↗
Headaches from chemical exposures.
Headaches are a common complaint after work place or environmental exposures. A striking index case led to a literature review which uncovered only limited information. We then performed a retrospective descriptive study of 50 subjects referred to University Clinics with the complaint of headaches associated with chemical exposures at their work place. Our data suggest a different headache may exist depending on whether the chemical exposure is routine and limited versus accidental and extensive. Low level work place chemical exposures appear to cause headaches that abate soon after cessation of the exposure. A single accidental and extensive exposure may lead to patient complaints of a new headache syndrome that may last from several months to years. The characteristics associated with the onset of a new headache syndrome from accidental chemical exposures includes: 1) An acute large quantity of exposure. 2) A short latency of onset of the heralding headache. 3) A severe intensity and long duration of the heralding headache. 4) New recurring headaches that were not experienced before the acute exposure. We suggest a possible term for this high exposure syndrome i.e. Chemical Headache Exposure Syndrome (CHES).
Adult↗
Community Hospital-based Stroke Programs: North Carolina, Oregon, and New York. I: Goals, objectives, and data collection procedures.
In order to assess the impact of variations in stroke care on outcomes, and to make geographic comparisons, the three Community Hospital-Based Stroke Programs in North Carolina, Oregon, and New York, aggregated their data on 4,132 hospitalized stroke patients. Complete demographic data or "Major Profile" were obtained on 2,390 (57.8%) of the 4,132 stroke patients. This includes those patients on whom informed patient and physician consents were obtained during the hospitalization. Of the major profile patients, 1,490 (62.3%) were followed for periods up to one year, 502 (21.0%) were lost to followup and 398 (16.6%) died within the one year followup period. Incomplete demographic data or "Minor Profile" were observed on 1,742 (42.1%) of the 4,132 patients. Minor profile includes those who died before comprehensive interviews were completed or those for whom informed consent for an interview could not be obtained. Of the minor profile group, 813 (46.7%) died in hospital, and 929 (53.3%) were alive when discharged from the hospital. This paper, which describes the programs, data collection procedures, and study cases, also highlights specific issues on stroke diagnosis, risk factors associated with stroke, and the influence of interventions on stroke outcomes. We conclude that: 1) the merging of data on hospitalized stroke cases from rural and urban hospitals in geographically distinct regions can be used in the study of stroke diagnosis, the use of diagnostic tests, and the effect of interventions on stroke outcomes; and 2) these data are consistent with the hypothesis that part of the national decline in mortality from stroke is due to a decline in stroke severity.
Adult↗
Community Hospital-based Stroke Programs: North Carolina, Oregon, and New York. II: Description of study population.
The three Community Hospital-based Stroke Programs collected data on 4132 stroke patients admitted to acute care hospitals during 1979 and 1980. White female stroke patients were older than the white male, nonwhite female and nonwhite male stroke patients. Nearly one-fourth (23%) of stroke patients were employed at the time of the event. Most (77%) of the patients were hospitalized for first stroke episodes. Eighty-three percent of the patients had at least one of the four major risk factors for stroke, namely, hypertension, diabetes, transient ischemic attacks and cardiac disease. Half (49%) of the patients were alert at the time of admission. The three diagnostic categories included infarction (60%), stroke not otherwise specified (30%) and hemorrhage (10%). Fourteen days was the median length of hospitalization; 50% of the stroke patients were discharged to a home setting, 31% were institutionalized and 19% died while in the hospital. The mean Barthel Index score for 2400 patients at the time of discharge was 61.8 (normal is 100). Of those patients who were working at the time of the stroke, 22% returned to work. In comparison to the patients in the National Survey of Stroke, patients in this Study were less severe at the time of admission (49% of patients in the National Survey of Stroke were stuporous or comatose compared to 21% of the patients in the current Study). The inhospital fatality was 30.7% in the National Survey of Stroke, and 19.7% in the current Study.
Activities of Daily Living↗
Community Hospital-based Stroke Programs: North Carolina, Oregon, and New York. III. Factors influencing survival after stroke: proportional hazards analysis of 4219 patients.
The possible effect of age, race, sex, consciousness upon admission, geographic location, and history of selected risk factors on the survival after stroke due to infarction or hemorrhage was determined using proportional hazards analysis (Cox regression). For each diagnostic category the most significant prognostic factor was consciousness upon admission. Increasing age, cardiac disease, or previous stroke also decreased the survival time of patients with infarctions. For patients with cerebral hemorrhage, no other variable was significant after control for consciousness level.
Adult↗
Evaluation of the North Carolina Stroke Care Program.
A study of 774 patients in eastern North Carolina was undertaken to determine the effects of a coordinated program of care and follow-up on recovery from stroke. The program was designed to coordinate and improve in-hospital stroke care and rehabilitation, to provide for education and training of the family for post-hospital care, and to coordinate and facilitate continued access to services after discharge. As measured by the Barthel Index at discharge, three, six and 12 months, the impact of the program was found to be minimal. Patients' scores throughout follow-up were influenced by age, whether the stroke event was new or recurrent, and the state of consciousness at admission. Follow-up Barthel scores were also related to scores obtained at discharge.
Activities of Daily Living↗