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Biomedical subjects

M Becker

Publications and source records attributed to M Becker.

At least 235 records · Page 13Linked to original sources
PubMed1993

Research and practice in medical education.

Education should be practiced with attention to principles derived from both the research in medical education and the practical experience of health professions instructors. The authors summarize both the major questions addressed by researchers in medical education during recent years and some of the answers. This paper is divided into four major categories of questions that correspond to the areas of an instructor's responsibility: 1) curricular trends, 2) instruction, 3) evaluation of learners, and 4) evaluation of teaching. It focuses largely on the undergraduate medical curriculum, although many of the conclusions could be applied to graduate education as well.

Education, Medical↗
PubMed1993

Carboplatin-liposomes as activators of hematopoiesis.

Recombinant colony stimulating factors are studied in clinical trials with the purpose being the relief of the side effects of high dose chemotherapy and to make an optimized treatment regimen possible. The broad use of such factors is hindered by their relatively high costs, their short elimination half-lives, the occurrence of mild side effects, and the limitation of their action to the stimulation of mainly neutrophils. Therefore, exogenous preparations inducing an endogenous activation of hematopoiesis are being sought. In experiments in mice we have shown that carboplatin-liposomes injected intraperitoneally in a single dose of 100 mg/kg led to a strong two-peak increase in white blood cell counts. A maximum 10-fold elevation compared to controls of free carboplatin or empty liposomes was observed on day 2 and was probably due to the release and mobilization of cells from storage compartments. The second peak of about a 6-fold increase occurred on day 7-8 and can be seen as an indicator of bone marrow stimulation. Differentiation of blood cells revealed that neutrophils, lymphocytes and platelets multiplied. We presume that this effect of carboplatin-liposomes is due to a relatively fast uptake of these vesicles by macrophages as their natural target. Within these cells carboplatin is metabolized, leading to an almost total loss of antineoplastic activity against the murine P388 leukemia. Concomitantly, cytokines are apparently induced in and released from macrophages producing secondarily hematopoietic growth factors either directly or in combination with other cytokines. An involvement of macrophages is indicated by the fact that an intraperitoneal pretreatment of mice with zymosan caused a partial but significant suppression of hematopoietic stimulation. In an in vitro colony forming assay of serum of mice treated 1, 3, or 7 days with carboplatin-liposomes, the number of colonies increased 20-fold compared to serum from saline treated animals. Additionally, a combined intraperitoneal treatment of mice with 100 mg/kg of cyclophosphamide followed by carboplatin-liposomes one hour later demonstrated that prevention of cytostatic-induced leukopenia is possible by this method. Although the mechanism of stimulation of hematopoiesis by carboplatin-liposomes is still partially unknown our results suggest that there should be further development of such a preparation for possible use in the treatment of cancer or other inherited or acquired hematopoietic disorders.

Animals↗
PubMed1993

Interferon gamma is effective for BM purging in a patient with CML.

We report a case of Ph-positive CML where the BM was incubated for 24 h with 10(3) IU/ml IFN gamma and then cultured in liquid media for 4 weeks. After 24 h incubation, there was no differential sensitivity of CML CFU-GM to IFN gamma compared with untreated BM. Subsequent long-term culture (LTC) of the IFN gamma treated CML BM, however, demonstrated a 75% inhibition of production of CFU-GM from the second week onwards. Using PCR, we were able to demonstrate two types of BCR-ABL transcript in the diagnostic BM. After 4 weeks of LTC, the J(bcr b3/ABL II) RNA transcript persisted in the untreated BM, whereas neither BCR/ABL RNA transcripts were detected in the culture established with IFN gamma-treated CML BM. This study has two points of interest with the demonstration of (1) a possible antileukaemic effect of IFN gamma on the progenitors generated in the LTC system, and (2) the use of highly sensitive PCR technology to evaluate the effectiveness of IFN gamma to purge CML BM of Ph-positive cells.

Bone Marrow↗
PubMed1993

Preventive medicine: what do future practitioners really need? Are they getting it in medical school?

The purposes of our study were (1) to determine preventive medicine topics most relevant to clinical practice, and (2) to determine if medical education affects medical students' attitudes regarding preventive medicine. Our method of study was two surveys. The first survey asked practicing physicians to rank the 23 topics identified in the Healthy People 2000 monograph and determine their usefulness in clinical practice. The second survey assessed medical students' attitudes about preventive medicine. Practitioners ranked tobacco, cancer, and diabetes as most relevant to the actual clinical practice of medicine. There were no correlations between practitioners' gender, age, or region and their rankings of topics. In terms of specialties, surgeons felt preventive medicine was less important than did family practitioners. Medical students' attitudes about preventive practices became significantly more positive as they progressed through medical school. Survey scores also improved significantly in second year students after their preventive medicine course. Students planning to be surgeons were less positive about preventive medicine. There is a continuing need for prevention education in medical school curricula, especially about tobacco, cancer, diabetes, and nutrition. Epidemiology and disease reporting might best be presented as "how to read the literature."

Adult↗
PubMed1992

Large-scale purification and characterisation of a recombinant epidermal growth-factor receptor protein-tyrosine kinase. Modulation of activity by multiple factors.

The human epidermal-growth-factor receptor (EGF-R) is a 170-kDa transmembrane glycoprotein that mediates the mitogenic response of cells to EGF and transforming growth factor alpha. Culture conditions have been developed for the large-scale expression of the cytoplasmic domain of the EGF-R in insect cells using a recombinant baculovirus. From 61 Sf9 cells, grown to high density using a bioreactor, 20 mg of the EGF-R kinase was purified to greater than 95% purity. Purification, which was carried out in the absence of detergents using classical purification methods, yielded an EGF-R protein that was not phosphorylated on tyrosine. This procedure has enabled us to produce high quality enzyme for both structural and biochemical studies on the EGF-R kinase. The in vitro activity of the cytoplasmic domain of the EGF-R kinase was modulated by multiple assay factors which include substrates, divalent cations and conformational modulators. Kinetic analysis in the presence of Mn2+ gave an apparent Vmax value of 20 nmol min-1 mg-1 and Km values of 4.5 microM for ATP and 1.43 mM for angiotensin II. This corresponds to a turnover number of 1.4 mol min-1 mol-1. Ammonium sulfate (1 M) resulted in an eightfold stimulation of kinase activity when assayed using angiotensin II as substrate. The specific activity of the intracellular domain of the EGF-R, when assayed at 20 degrees C in the presence of 1M ammonium sulfate, was 160 nmol min-1 mg-1. Activation of the EGF-R kinase by ammonium sulfate was found to be substrate-specific. No activation was found when assayed using polymeric substrates. Addition of Me(2+)-ATP to the purified enzyme resulted in autophosphorylation and was accompanied by retardation of SDS/PAGE migration. Kinetic constants and metal ion preferences of a number of co-polymers and peptide substrates have been compared. Dramatic differences in kinetic constants were found which were dependent on both the substrate and metal ion used. Activation of EGF-R autophosphorylation was found to be influenced by the use of charged polymers. The random polymer of Glu, Lys, Ala, Tyr (2:5:6:1), which was not phosphorylated by the EGF-R kinase, dramatically activates autophosphorylation of the EGF-R. Thus the intracellular domain of the EGF-R appears to be in a low-activity conformation which, under appropriate assay conditions, can be activated to a similar specific activity to that reported for the purified EGF-R holoenzyme.

Angiotensin II↗
PubMed1992

Characterization of two human mammary carcinomas, MT-1 and MT-3, suitable for in vivo testing of ether lipids and their derivatives.

The human mammary carcinomas MT-1 and MT-3 originate from surgical material and were transplanted in nude mice. Both tumors have been classified as estradiol- and progesterone receptor-negative. Therapeutic doses of hormones and anti-hormones remained without growth inhibitory effect. MT-1 and MT-3 proved to be sensitive to conventional cytostatic drugs used for treatment of mammary carcinomas; striking is their sensitivity to ether lipids. Therefore, they are considered suitable tumor models for this class of substances.

Animals↗
PubMed1992

Correlation of hepatitis B virus, hepatitis D virus and human immunodeficiency virus type I infection markers in hepatitis B surface antigen positive haemophiliacs and patients without haemophilia with clinical and histopathological outcome of hepatitis.

The hepatitis D virus (HDV) infection plays a major role in severe liver damage caused by hepatitis. To establish the prevalence of HDV infection in haemophilic patients and patients without haemophilia, 87 patients with chronic hepatitis B virus (HBV) infection were examined for serological evidence of delta hepatitis. In addition HBV, HDV and human immunodeficiency virus type 1 (HIV) infection markers were compared to clinical and histopathological outcome of hepatitis. Out of 46 haemophiliacs 30 (65%) were anti-HD-seropositive; 10 out of 30 anti-HD-positive patients (33%) had pathological liver function tests compared to 2 out of 16 anti-HD-negative haemophiliacs (13%). The rate of HIV infection did not differ between the HDV infected and the non-HDV infected individuals with haemophilia (17/27 anti-HD-positive patients versus 12/16 anti-HD-negative patients). Two haemophilic anti-HD-positive patients underwent liver biopsy, in both cases hepatitis D antigen (HDAg) was detected in the biopsies. Only 2 out of 41 patients without haemophilia were anti-HD-positive. Both had pathological liver function tests; chronic active hepatitis and cirrhosis, respectively, were diagnosed and HDAg was found in the liver biopsies. Out of 39 anti-HD-seronegative patients without haemophilia, 26 (67%) were hepatitis B e antigen positive; in the sera of 20 patients (51%) HBV-DNA was demonstrated, but only 6 patients (15%) had pathological liver function tests. In conclusion a high seroprevalence of HDV infection was found in haemophilic patients treated with non-pasteurized commercial clotting factor concentrates. An endemic spreading of HDV infection in patients without haemophilia with chronic HBV infection could not be detected.(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome↗
PubMed1992

Presentation of drug prescribing guidelines and physician response.

Most Medicaid Drug Use Review (DUR) Programs disseminate prescribing practice guidelines by providing written reviews to physicians about specific prescribing practices that do not follow established criteria and inviting their comment. This study reviewed physicians' written responses to explore relationships between DUR communications and the degree to which these communications affect awareness of prescribing issues, increase knowledge, change erroneous beliefs, and generate intentions to apply the information appropriately. The form, content, and effective tone for all responses received in 1990 regarding five different drug therapy issues (N = 240) was recorded. Response rates, comprehension, counterarguments, and prescribing intentions varied by drug therapy issue. Attention to the communication process could improve the dissemination of prescribing practice guidelines by DUR Programs.

Attitude of Health Personnel↗
PubMed1992

Assessing Alzheimer severity with a global clinical scale.

Diagnosis of dementia needs to be complemented by precise determination of disease severity across the broad spectrum of disease progression. The Mini-Mental State Exam (MMS), the Activities-of-Daily-Living assessment (ADL) and the Clinical Dementia Rating scale (CDR) were modified for direct comparability and administered to 112 outpatients and 45 nursing home residents with a range of dementia severity from mild to profound. The scales showed the highest correlations for the probable Alzheimer's disease patient group (62) (Global Assessment of Dementia; GAD vs. ADL: r = 0.91; Extended Mini-Mental Assessment; EMA vs. GAD: r = 0.91; ADL vs. EMA: r = 0.86). For these patients, scores on the individual scales tended to be similar. Disparity among the three scores for individual cases was associated with the presence of comorbidities. The high correlations and correspondence among these scales demonstrate their reliability, validity, and utility in the assessment of dementia severity. The use of an average of these measures, with their increased precision, may give a more accurate indication of dementia severity over a broader range of impairment.

Activities of Daily Living↗
PubMed1992

[Diagnosis and therapy of tendinitis exemplified by the athletic horse].

This paper reviews the literature and describes our experiences in the diagnosis and treatment of tendinitis in horses. Ultrasonography provides a sensitive tool to diagnose tendinitis and quantitate the degree of damage to the tendon; as well as provide differential diagnoses such as peritendinitis. The principles in therapy of acute tendinitis are: Immediate reduced exercise or rest, physical therapy to reduce inflammation and administration of local and systemic antiinflammatory drugs. The goal is restoration of the tensile strength of the tendon without peritendinous granulation tissue and adhesions. To achieve this goal it is important to maximize the intrinsic healing and to minimize the extrinsic healing. Any form of counterirritation is forbidden because of increase of inflammation. Passive motion and massage will help to increase blood flow and to decrease adhesions. Local injection (peritendinous and intratendinous) of hyaluronic acid seems to increase the intrinsic healing and to decrease adhesions without side effects. Depending on the extent of the tendon damage, which tendon is involved and the progress toward healing controlled ultrasonographically, the healing period can be divided in 4 phases: 1. Immobilisation (Cast), only in severe cases (for 1-2 weeks). 2. Passive motion and massage (starting as soon as possible, usually at once during bandage change). 3. Careful exercise, hand walk or walk under saddle (for 1-6 months, starting as soon as possible, usually about 5 days after initial treatment). 4. Controlled slow and gradual training, no turnout, long or pasture (for 1-6 months, after phase 3). Chronic tendinitis is often caused when the severity of the initial injury is underestimated and the treatment inappropriate. Chronic tendinitis is treated using similar principles starting with phase 2. Tendon splitting and other surgical approaches have been used in selected cases to enhance the prognosis.

Animals↗
PubMed1992

Nurse's aides in nursing homes: the relationship between organization and quality.

This study examines the work of the nurse's aide through a combination of participant observation and in-depth interviews with 30 nurse's aides. Data were analyzed using the grounded theory method of constant comparative dimensional analysis. Findings suggest that strategies developed by individual nurse's aides to organize their work are important determinants of both the quality of care and worker turnover. Quality of care may be better explained by Litwak's theory about the difficult juxtaposition between primary and formal groups than by the nurse's aides' lack of knowledge.

Adult↗
PubMed1992

Anti-myeloperoxidase autoantibodies react with native but not denatured myeloperoxidase.

We wondered whether anti-myeloperoxidase (MPO) autoantibodies (MPO-ANCA) found in patients with systemic vasculitis react with a conformational epitope or epitopes on the MPO molecule. Sera from 15 human MPO-ANCA, and a polyclonal and a monoclonal anti-MPO antibodies were reacted with MPO in native and denatured states. Human MPO-ANCA and mouse monoclonal anti-MPO reacted with native MPO, and a 120-kD band representing the MPO hologenzyme, but not with denatured MPO fragments; however, MPO-ANCA and mouse anti-MPO did not demonstrate competitive inhibition of binding to MPO. Polyclonal rabbit anti-MPO reacted with both native and denatured MPO. All MPO-ANCA tested showed the same patterns of reactivity with native and denatured MPO in dot blot and Western blot analyses. Both polyclonal and monoclonal anti-MPO antibodies inhibited MPO's protein iodination by over 90%, whereas MPO-ANCA IgGs, normal IgGs and disease control IgGs did not. These data suggest that (i) MPO-ANCA interact with a conformational epitope on the MPO molecule; and (ii) MPO-ANCA from different patients have similar reactivity with native versus denatured MPO.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed1992

Delusions and behavioral disturbances in cognitively impaired elderly persons.

OBJECTIVE: To compare cognitive function and the prevalence of selected behavioral problems in delusional and non-delusional dementia patients. DESIGN: Retrospective medical record review. SETTING: An outpatient geriatric assessment center. PARTICIPANTS: 114 consecutive patients with dementia. MAIN OUTCOME MEASURES: Delusions as recorded in a consultation report. RESULTS: Delusions were described in 25.5% of patients. A variety of behavioral disturbances were more common in delusional than non-delusional patients, including agitation, angry or hostile outbursts, urinary incontinence, wandering or pacing, and insomnia. While cognitive function as measured by the MMSE was similar in delusional and non-delusional patients (18.9 +/- 3.8 and 19.2 +/- 5.9, respectively), there was a statistically borderline tendency for delusions to occur more often in patients in the mid-range of cognitive impairment (17 less than or equal to MMSE less than or equal to 23) compared with patients with greater or lesser degrees of cognitive impairment (32% vs 17% respectively). CONCLUSION: Delusions in dementia are associated with a variety of behavioral problems. Further studies are needed to clarify the role of delusions in the development of disruptive behaviors in dementing illness.

Aged↗
PubMed1992

Intravenous immunoglobulin in HIV-I infected haemophilic patients.

In order to evaluate the efficacy of intravenous immunoglobulin (IVIG) in the early stages of HIV infection (patients without AIDS or AIDS related complex) a prospective controlled open trial was conducted in 36 patients (age 6-19 years) with haemophilia. Eighteen patients received 0.3 g/kg IVIG at two week intervals; 18 patients served as controls. Major criteria for the evaluation were progression of HIV disease assessed by the modified Brodt/Helm classification, number of infectious events and HIV associated thrombocytopenia, and the CD4+ T cell count. After 24 months of evaluation seven patients in the IVIG group and five patients in the control group deteriorated according to their staging, with one patient in each group developing AIDS. Thrombocytopenia and infectious events, but no severe bacterial infections, occurred in both groups in similar numbers. The absolute CD4+ T cell count decreased by 284/microliters in the IVIG group and by 143/microliters in the control group respectively (mean values). The statistical analysis of these criteria did not reveal any significant difference. In conclusion, IVIG was not effective in the early stages of HIV infection in patients with haemophilia. IVIG did not slow down the progression of HIV disease and did not prevent the development of an immunodeficiency as assessed by the CD4+ T cell count.

Adolescent↗
PubMed1992

Attenuation of postischemic microvascular disturbances in striated muscle by hyperosmolar saline dextran.

The underlying mechanisms of the beneficial therapeutic effects of small-volume resuscitation with hyperosmolar solutions for treatment of hypovolemic shock are still poorly understood. Using the dorsal skinfold chamber model and intravital fluorescence microscopy, we investigated the effects of hyperosmolar saline dextran on ischemia-reperfusion injury in striated skin muscle of awake normovolemic golden hamsters. Test solutions (4 ml/kg body wt i.v.) were administered 2 min before reperfusion after 4 h of pressure-induced ischemia. In animals receiving 0.9% saline (control), we observed a drastic enhancement of leukocyte rolling along and sticking to the endothelium of postcapillary venules 0.5 h after reperfusion. Postischemic leukocyte rolling and sticking were significantly reduced when animals were treated with 7.2% saline alone (HSS), 10% Dextran 60 in 0.9% saline (HDS), or 10% Dextran 60 in 7.2% saline (HHS). In control animals, capillary perfusion was reduced to approximately 60% of preischemic values 0.5 h after reperfusion. Concomitantly, leakage of the macromolecule fluorescein isothiocyanate-dextran (5 mg in 0.1 ml saline i.v., M(r) 150,000) into the perivascular space increased from 0% before ischemia to approximately 12% at 0.5 h reperfusion. In contrast, when animals were treated with HSS, HDS, or HHS before reperfusion, capillary perfusion decreased to a significantly minor extent of approximately 15%, and macromolecular leakage was slightly increased to approximately 5%. Our results suggest that hyperosmolar saline dextran effectively attenuates postischemic microvascular disturbances elicited by ischemia-reperfusion, presumably through reduction of postischemic leukocyte-endothelium interaction and capillary swelling.

Animals↗