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Biomedical subjects

S Haas

Publications and source records attributed to S Haas.

At least 145 records · Page 8Linked to original sources

Influence of dexniguldipine-HC1 on rhodamine-123 accumulation in a multidrug-resistant leukaemia cell line: comparison with other chemosensitisers.

In the clinical therapy of cancer, resistance to many cytostatic drugs is a major cause of treatment failure. Among other mechanisms, the expression and pumping activity of P-glycoprotein (PGP) in the membrane of resistant cancer cells is responsible for the reduced uptake of cytostatics. The blockade or inhibition of PGP activity by chemosensitisers seems to be a tenable way to restore sensitivity to antineoplastic drugs and therapeutic efficacy. In the present work the influence of the new chemosensitiser dexniguldipine on rhodamine-123 accumulation in multidrug-resistant leukaemia cells was investigated. Dexniguldipine increases cellular rhodamine-123 accumulation dose-dependently.pEC50 values (-log concentration of drug showing a half maximal effect) in accumulation studies are dependent on pH of the test system and are in the range of 6.5 (pH 7.2) to 7.2 (pH 8.0) for dexniguldipine. In comparison with other chemosensitisers such as SDZ PSC 833, cyclosporin A, verapamil, dipyridamole, quinidine and amiodarone, dexniguldipine is the most potent drug in this test system. In addition to equilibrium measurements of rhodamine-123 accumulation, efflux of rhodamine-123 was analysed in the absence and presence of chemosensitisers. A clear dose-dependency was seen and, moreover, a dramatic decrease in efflux rates was achieved in the presence of chemosensitisers. The described system can be used to investigate PGP-mediated drug transport on a pharmacological and biochemical basis.

Antineoplastic Agents↗

Phase I--study with aprosulate, a new synthetic anticoagulant.

This paper describes the first human study with aprosulate, a new chemically synthesized anticoagulant with a defined molecular structure and a molecular weight of 2388. Twelve healthy male volunteers received subcutaneous injections of placebo on the first day followed by ascending doses of aprosulate in the range of 0.25 mg/kg to 2.0 mg/kg body weight on alternate days. Anticoagulant, pharmacokinetic and safety parameters were assessed for 48 hours after each injection. The activated partial thromboplastin time and the Heptest showed a dose-dependent increase for up to ten hours after each application. A trend towards prolongation of the bleeding time was indicated with higher doses. In general, the tolerance was good. Plasma transaminase concentrations were raised in some volunteers but returned spontaneously to normal during or after the study.

Adolescent↗

Fine needle aspiration of thyroid nodules in a rural setting.

PURPOSE: The purpose of this study was to evaluate the applicability of fine needle aspiration biopsy (FNAB) of thyroid nodules in rural practices with smaller patient numbers, to assess the effect of these numbers on the results, and to establish the level of accuracy of the procedure in this setting. PATIENTS AND METHODS: We retrieved all thyroid FNAB reports identified as being performed by a single practitioner in a referral endocrine practice in Rapid City, South Dakota, between September 30, 1987, and September 30, 1991. Biopsy results are separated by year to establish correlations with the number of biopsies and outcomes. Follow-up pathology reports were obtained for all patients known to have undergone surgery. RESULTS: A total of 189 FNABs in 165 patients were available for review from a 4-year period. The number of FNABs increased progressively from 28 per year to 65 per year during the 4-year course of the study. The incidence of inadequate specimens decreased inversely from 18% to 6% with the increase in the number of FNABs. The percentage of surgical interventions in which malignancy was found increased from 23% to 50% over the same period. Analysis of the results suggests that accuracy and specificity are comparable to results from larger centers. CONCLUSIONS: FNAB of thyroid nodules can substantially reduce surgical intervention and increase the yield of malignancy without excessive loss of accuracy even in rural areas with small numbers of patients. Improved results as the number of biopsies increased to 50 or more per year suggest benefits from concentrating biopsies with as few operators as practical.

Aftercare↗

Variation in hysterectomy rates across small geographic areas of Massachusetts.

OBJECTIVE: Our objective was to determine whether small-area variation in hysterectomy rates exists within Massachusetts and, if so, whether regions with persistently high or low rates can be identified. STUDY DESIGN: By examining data derived from standardized hospital discharge forms between 1982 and 1989, we compared hysterectomy rates among 172 small geographic areas within Massachusetts. The ratios of actual to expected number of hysterectomies for each area were also computed. Statistical significance of rate variation was established by a value of p < 0.01 (chi 3 test). RESULTS: The-hysterectomy rate per 1000 women varies fivefold across small-population areas of Massachusetts. Eight areas had persistently high and five had persistently low rates compared with the statewide average. CONCLUSION: Possible explanations for these rate variations include indigenous population factors, supply of health care resources, income, insurance coverage, methodological problems in data analysis, and variation in professional judgment with regard to the indication for hysterectomy. Only a combination of the study of local causes of high and low rates and the study of the clinical outcomes of different treatment decisions will allow physicians to develop an informed consensus on appropriate indications for surgery.

Female↗

Administrative rounds. A neglected art.

In making decisions, nurse administrators need diverse information from a variety of sources. One source of this information can be administrative rounds. Rounds not only offer opportunity for data collection and verification, problem identification and remediation, but they also provide an opportunity for coaching of staff and leadership visibility. The outcome of nursing work can be enhanced by nurse administrators seeing and being seen.

Communication↗

Procedural complications of electroconvulsive therapy: assessment and recommendations.

We surveyed procedural techniques in 804 routine clinical sessions of electroconvulsive therapy (ECT) over 4 2/3 years. No significant problems occurred. Side effects as agitation, physical complications such as urinary stasis, and protocol deviations such as failure to use the bite block were occasionally documented. Mechanical difficulties such as trouble gaining intravenous access and medicinal problems such as inappropriate dosing were rare. Our assessment resulted in a more precise method of diminishing the risks of ECT. For example, the chin is held manually, closing the mouth during delivery of the stimulus, to obviate oral trauma. Similarly, electrode contact is always verified visually and with the ECT machine "self-test" just before each treatment. Both cuff and electroencephalographic means are used to determine seizure timing. ECT is safe; a carefully applied protocol should make it safer.

Adolescent↗

A developmentally regulated DNA-binding protein from mouse brain stimulates myelin basic protein gene expression.

Transcription of the myelin basic protein (MBP) gene is regulated in a cell-type-specific and developmental stage-specific manner during myelin formation in the murine central nervous system. The 5'-flanking region of the MBP gene contains several regulatory elements that differentially contribute to the cell-type-specific transcription of MBP in cells derived from the central nervous system. The proximal element, termed MB1, which is located between nucleotides -14 and -50 with respect to the RNA start site, has previously been shown to have characteristics of a cell-type-specific enhancer element. In this study, we used band shift and UV cross-linking assays to identify DNA-binding proteins in mouse brain nuclear extract which interact with the MB1 element. Fractionation of these extracts has allowed the identification of a 38- to 41-kDa nuclear protein, derived from mouse brain tissue at the peak of myelination, which specifically binds the MB1 DNA sequence. Fractions enriched in the MB1-binding protein have been shown to stimulate transcription of the MBP promoter in extract derived from HeLa cells. MB1 binding protein activity is expressed in a tissue-specific and development stage-specific pattern which coincides with the pattern of MBP transcription, suggesting that this protein may be a biologically relevant transcription factor for the MBP gene in vivo.

Aging↗

European consensus statement on the prevention of venous thromboembolism. European Consensus Conference, Windsor, U.K., November, 1991.

Since the Consensus Conference of the National Institute of Health in 1986, the developments in the field of prevention of venous thromboembolism were mainly characterized by a more specific and extended use of new prophylactic agents such as low molecular weight heparins as well as the perception that outpatients may be at risk for thromboembolic complications, too. Therefore, in November 1991, a European Consensus Conference on the prevention of thromboembolism was held in Windsor, UK, in order to analyse the risk constellation of various patient populations and to give recommendations for primary prophylaxis in general surgery, urology, neurosurgery, orthopaedic and trauma surgery, obstetrics and gynaecology and medical patients. In addition, the cost-effectiveness of the various methods was highlighted, and the question of secondary prevention addressed. The meeting was organized under the patronage of the European Economic Commission, and experts from 15 different countries were invited to participate. The conference was organized according to acknowledged guidelines of consensus conference organization, i.e. each expert had to formulate his provisional standpoint, the working documents were compiled by the organizer, and this file was sent to the delegates before the conference. During the first part of the meeting, the delegates presented their views in plenary sessions. Controversial points were discussed in working groups, and the results were discussed in plenary sessions. Consensus or lack of accord was documented and the open questions were formulated in order to be answered by future studies. The published statements and recommendations are based on different levels of evidence.(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical Trials as Topic↗

[Therapy of thromboses with low molecular weight heparins].

The most commonly used therapy of thromboembolism consists of continuous intravenous infusions of heparin followed by a treatment with oral anticoagulants. A new aspect of this classical therapy is the possibility of subcutaneous administrations of heparin b.i.d. and, that heparin may be replaced by low molecular weight heparins. The therapy with low molecular weight heparins can be further simplified by only single daily injections and doses regimens which are adjusted to the patient's body weight and which do not require an individual laboratory monitoring.

Drug Administration Schedule↗

Prevention of postoperative thromboembolism with Enoxaparin in general surgery: a German multicenter trial.

The antithromboembolic efficacy and safety of Enoxaparin, a low molecular weight heparin preparation, has been studied in a multicenter prospective randomized trial in 10,032 patients scheduled for a variety of elective general surgical, gynecologic, and urologic procedures. There were 9919 patients operated on and who received Enoxaparin, of whom 9907 patients were randomized into two groups. The morning group, composed of 4987 patients, received a subcutaneous injection of 20 mg Enoxaparin 2 hours before surgery and each morning for 7 postoperative days. The evening group, composed of 4920 patients, received the identical injection the evening before surgery and postsurgically for 7 days in the evening. Both groups were comparable in age, gender, weight, surgical category, anesthesia, and any risk factors that could predispose to the development of DVT or PE. The objective of this study was to detect efficacy and safety of Enoxaparin 20 mg under typical clinical conditions. The results were the following: PE was reported in 24 patients, leading to an incidence of PE under Enoxaparin prophylaxis of 0.24% in total, 0.21% for nonfatal and 0.03% for fatal PE. There were no differences in the incidence between the morning and evening groups. The incidence of DVT diagnosed by clinical signs was found to be 0.11%, with six cases in the morning group and five cases in the evening group. An analysis of operative and postoperative bleeding showed no difference between the groups in terms of blood transfusion requirements and drainage volumes, excessive bleeding in the wound area, or other bleeding complications. There was a slight postoperative decrease in haemoglobin and hematocrit in both groups. However, no severe Enoxaparin-induced thrombocytopenia was observed. Only 71 patients (0.72%) reported adverse drug reactions, most of which were local reactions. The results from this study indicate that a single daily injection of 20 mg Enoxaparin is a safe and efficient prophylaxis for thromboembolic complications in patients undergoing any of a variety of general surgical procedures. This study indicates that prevention of thromboembolism is not strictly limited to a 2-hour interval between start of prophylaxis and onset of surgery but may also be provided by starting prophylaxis with 20 mg Enoxaparin during the evening before surgery and continuing treatment postoperatively.

Adult↗

[Observations on pathophysiology and pathogenesis of venous thrombosis].

Even today, Virchow's triad is still a useful method for describing the circumstances under which thrombosis can occur. To investigate the underlying pathophysiological principles, however, the methods must differentiate more clearly. Only recently, the complicated interactions of blood coagulation and fibrinolysis have been described. Although detailed determinations of markers of activated coagulation and fibrinolysis can be performed, it has not been possible to achieve a reliable screening method to indicate the individual patient's risk. Alterations in the endothelial cells seem to play a key role in thrombogenesis. The clinician's interest in thrombosis research is based on several open or insufficiently answered questions, such as why thrombosis can occur in veins for away from the site of the operation, whether reliable and simple screening methods can be established in order to determine the patient's risk constellation, and how the methods of preventing thrombosis and administering therapy can be improved.

Blood Coagulation↗