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Biomedical subjects

L Weber

Publications and source records attributed to L Weber.

At least 73 records · Page 4Linked to original sources
PubMed1998

Light reflection rheography and clinical course of patients with advanced venous disease before and after endoscopic subfascial division of perforating veins.

BACKGROUND: Endoscopic subfascial division of perforating veins (ESDP) has been shown to cause fewer surgical complications than classic techniques. OBJECTIVE: To evaluate the efficacy of ESDP based on patients' symptoms, rheographic data, and ulcer healing. METHODS: Thirty-two subsequent patients underwent 40 ESDP procedures. Fifteen limbs presented with a postthrombotic syndrome (PTS), and 16 cases had an active venous ulcer. Data were recorded before and 2 months after ESDP. Stripping or high ligation procedures had been previously performed. RESULTS: The symptoms of pain and edema improved in 80% (PTS) and 74% (venous ulcer) of patients. Only one case did not show improvement of either pain or edema. Fifty-eight percent of patients showed hemodynamic improvement by light reflection rheography (LRR), while 32% did not change and 10% of patients had a worsened LRR after ESDP. The LRR refilling times increased by a median factor of 1.69, reaching at least 20 seconds in nine of 40 limbs. Venous ulcers that had been active for a median of 12 years (range, 0.5-21) healed in nine of 16 cases within 14-50 days (median, 21 days). CONCLUSION: ESDP reduces disease-related symptoms, improves hemodynamics in almost 60%, and facilitates healing of long lasting venous ulcers.

Adult↗
PubMed1997

Identification of novel farnesyl protein transferase inhibitors using three-dimensional database searching methods.

Generation of a three-dimensional pharmacophore model (hypothesis) that correlates the biological activity of a series of farnesyl protein transferase (FPT) inhibitors, exemplified by the prototype 1-(4-pyridylacetyl)- 4-(8-chloro-5,6-dihydro-11H-benzo [5,6]cyclohepta[1,2-b]pyridin-11-ylidene)piperidine, Sch 44342, 1, with their chemical structure was accomplished using the three-dimensional quantitative structure-activity relationship (3D-QSAR) software program, Catalyst. On the basis of the in vitro FPT inhibitory activity of a training set of compounds, a five-feature hypothesis containing four hydrophobic and one hydrogen bond acceptor region was generated. Using this hypothesis as a three-dimensional query to search our corporate database identified 718 compounds (hits). Determination of the in vitro FPT inhibitory activity using available compounds from this "hitlist" identified five compounds, representing three structurally novel classes, that exhibited in vitro FPT inhibitory activity, IC50 < or = 5 microM. From these three classes, a series of substituted dihydrobenzothiophenes was selected for further structure-FPT inhibitory activity relationship studies. The results from these studies is discussed.

Alkyl and Aryl Transferases↗
PubMed1997

Trauma in pregnancy: normal Revised Trauma Score in relation to other markers of maternofetal status--a preliminary study.

OBJECTIVE: Our goal was to examine whether a correlation exists between the Revised Trauma Score assigned on admission and pregnancy outcome, as well as whether the Revised Trauma Score has any predictive value for optimal duration of cardiotocographic monitoring necessary to detect immediate adverse pregnancy outcome. STUDY DESIGN: A retrospective chart review was performed of 30 pregnant trauma patients admitted during a 1-year period. Evaluation of cardiotocographic data for either contractions or decelerations or both was performed without knowledge of Revised Trauma Score or maternofetal outcome at discharge. RESULTS: Review of uterine activity and fetal decelerations did not detect useful predictive patterns unless the tracing was immediately ominous, although uterine activity did initially decrease over time. CONCLUSIONS: The Revised Trauma Score lacks predictive value for both risk of adverse pregnancy outcome and need for prolonged cardiotocographic monitoring. A larger patient population needs to be studied for an accurate determination of whether the Revised Trauma Score has potential as a predictive tool.

Cardiotocography↗
PubMed1997

Molecular recognition at the thrombin active site: structure-based design and synthesis of potent and selective thrombin inhibitors and the X-ray crystal structures of two thrombin-inhibitor complexes.

BACKGROUND: The serine protease thrombin is central in the processes of hemostasis and thrombosis. To be useful, thrombin inhibitors should combine potency towards thrombin with selectivity towards other related enzymes such as trypsin. We previously reported the structure-based design of thrombin inhibitors with rigid, bicyclic core structures. These compounds were highly active towards thrombin, but showed only modest selectivity. RESULTS: Here, we describe the rational design of selective thrombin inhibitors starting from the X-ray crystal structure of the complex between the previously generated lead molecule and thrombin. The lead molecule bound with a Ki value of 90nM and a selectivity of 7.8 for thrombin over trypsin. Our design led to inhibitors with improved activity and greatly enhanced selectivity. The binding mode for two of the new inhibitors was determined by X-ray crystallography of their complexes with thrombin. The results confirmed the structures predicted by molecular modeling and, together with the binding assays, provided profound insight into molecular recognition phenomena at the thrombin active site. CONCLUSIONS: A novel class of nonpeptidic, selective thrombin inhibitors has resulted from structure-based design and subsequent improvement of the initial lead molecule. These compounds, which are preorganized for binding to thrombin through a rigid, bicyclic or tricyclic central core, could aid in the development of new antithrombotic drugs. Correlative binding and X-ray structural studies within a series of related, highly preorganized inhibitors, which all prefer similar modes of association to thrombin, generate detailed information on the strength of individual intermolecular bonding interactions and their contribution to the overall free energy of complexation.

Antithrombins↗
PubMed1997

Build-up cap materials for measurement of photon head-scatter factors.

The suitability of high-Z materials as build-up caps for head-scatter measurements has been investigated. Build-up caps are often used to enable characterization of fields too small for a mini-phantom. We have studied lead and brass build-up caps with sufficiently large wall thicknesses, as compared to the range of contaminating electrons originating in the accelerator head, and compared them with build-up caps made of ionization chamber equivalent materials, i.e. graphite. The results were also compared with measurements taken using square and cylindrical polystyrene mini-phantoms. Field sizes ranging from 3 cm x 3 cm up to 40 cm x 40 cm were studied for nominal photon energies of 4, 6, 10 and 18 MV. The results show that the use of lead and brass build-up caps produces normalized head-scatter data slightly different from graphite build-up caps for large fields at high photon energies. At lower energies, however, no significant differences were found. The intercomparison between the two different plastic mini-phantoms and graphite caps showed no differences.

Alloys↗
PubMed1996

Effect of overexpression of the small heat shock protein HSP27 on the heat and drug sensitivities of human testis tumor cells.

In contrast to most metastatic cancers, testicular germ cell tumors are cured in more than 80% of patients using cisplatin-based combination chemotherapy. Testis tumor cells in vitro retain their sensitivity to chemotherapeutic drugs, radiation, and other stresses, such as heat shock. Having shown that this is associated with low constitutive levels of heat shock protein (HSP) 27, we determined the effect of overexpression of HSP27 on the heat and drug sensitivities of a human testis tumor cell line, 833K. Cells were cotransfected with plasmids containing a neomycin resistance gene and the full-length human HSP27 gene, and four clones that overexpressed HSP27 by factors of 3.7-38.3-fold compared with the parental cells were selected. The overexpressing cells were more resistant to heat shock, cisplatin, and doxorubicin, and this was associated with modest increases (17-30%) in population doubling times and a small reduction in the number of S-phase cells. These results suggest that the low constitutive levels of HSP27 in testis tumor cells may contribute to the sensitivity of testicular germ cell tumors to chemotherapy, and that targeting HSP27 may improve response rates in other types of cancer.

Biological Transport↗
PubMed1996

[Behçet disease with primary involvement of the cerebral vessels].

HISTORY AND CLINICAL FINDINGS: Two months after the onset of mainly frontal headaches a 25-year-old man of Turkish descent additionally developed double vision. Fundoscopy revealed bilateral choked discs and right trochlear paralysis. Computed tomography and digital subtraction angiography demonstrated thrombosis of the superior sagittal sinus. On admission to hospital the patient was fully conscious but had marked meningism, bilaterally positive Lasègue's sign (painful straight leg raising) at a 50 degree angle, and multiple oral aphthous ulcers. The sinus thrombosis suggested a chronic inflammatory process, while the oral ulcers pointed to Behçet's syndrome. INVESTIGATIONS: Inflammatory parameters (erythrocyte sedimentation rate, C-reactive protein and white blood cell count) were increased and the HLA-B27 test was positive. Other laboratory tests, cerebrospinal fluid, chest radiogram and ECG were unremarkable. TREATMENT AND COURSE: Despite intravenous administration of heparin nad cefuroxim for one week the sagittal sinus thrombosis spread to the straight sinus. In the third week scrotal ulcerations were noted and taken to confirm Behçet's syndrome. Immunosuppressive treatment with methylprednisolone (initially 80 mg daily) and 2 weeks later together with chlorambucil (0.1 mg/kg daily) was started. Four weeks later the patient was free of symptoms and discharged. CONCLUSION: Neurological signs are not adequately stressed by the International Study Group for Behçet's Disease among its listed diagnostic criteria.

Adult↗
PubMed1996

Tolerance to intravenous administration of heparin and heparinoid in a patient with delayed-type hypersensitivity to heparins and heparinoids.

Delayed-type hypersensitivity reactions to subcutaneously (s.c.) injected heparins are common. Since similar reactions usually occur to different heparin preparations, semisynthetic heparinoids might be a therapeutic alternative. We report a patient exhibiting eczematous reactions to heparins as well as heparinoids; delayed-type hypersensitivity was demonstrated by intracutaneous (i.c.) and patch tests, as well as by s.c. provocation. Remarkably, intravenous (i.v.) administration of heparin as well as heparinoid was well-tolerated.

Anticoagulants↗
PubMed1996

Verification and implementation of dynamic wedge calculations in a treatment planning system based on a dose-to-energy-fluence formalism.

The use of dynamic movements on linear accelerators during irradiation has found a revised interest lately due to the integration of computers to control the accelerator. In this paper, dynamic wedge fields that are produced by moving one of the collimator blocks during irradiation are studied. Since these wedge fields differ from those of mechanical wedges, certain requirements are to be met on the treatment planning system. A pencil-beam-based treatment planning system that uses the resultant energy fluence distribution from the dynamic collimator movement has been extensively reviewed. In calculations, the system treats the dynamic collimated field as a single, modulated field that yields calculation times close to those for open beams. Details are given on the theoretical model used for the calculation of dynamically generated dose distributions. Measurements of depth doses, profiles, and output factors in dynamic wedge fields indicate that calculations accurately predict the outcome from dynamic wedges without any additional measurements other than those used for characterization of static open beams.

Biophysical Phenomena↗
PubMed1996

Psychosocial correlates of chest pain among African-American women.

While 10-30% of individuals with chest pain who undergo cardiac arteriography are found to have no demonstrable pathology, women are far more likely than men to have normal coronary arteries in the presence of angina. Black women, in particular, frequently seek medical attention for persistent episodes of chest pain. This cross-sectional study was designed to examine the potential role of psychological and social factors in relation to chest pain among black women. Among our population-based sample of 188 women, 48% reported experiencing chest pain. Seventeen of these cases met the Rose criteria for classification as cardiac pain while 74 of them reported pain not consistent with cardiac origin. A statistically significant difference was observed in the stress scores among the women; the highest stress scores occurred among those with Rose angina and the lowest scores were obtained from those women reporting no chest pain experiences (p < 0.001). There was no association detected between the presence and type of chest pain and psychosocial measures of depression and coping abilities. These results confirm the high rates of chest pain experienced among black women, and provide insight into the role of psychological factors that should be considered in the identification of treatment options.

Adult↗
PubMed1995

[Calciphylaxis].

HISTORY AND CLINICAL FINDINGS: Acute, zigzag-shaped livid skin markings developed on both thighs of a 55-year-old woman who had been on dialysis for 6 years. Within 7 days these areas increased in size to about 10 cm in diameter and contained central dry and painful necroses. On legs, lower arms and hands hard subcutaneous nodules were palpable with a diameter up to 3 mm. For many years the phosphate and parathormone levels, as well as alkaline phosphatase activity had been raised. The patient had often failed to follow treatment recommendations. TESTS: There were increased serum concentrations of calcium (2.8 mmol/l) and phosphate (1.78 mmol/l). The calcium phosphate ion product was 4.98 (mmol/l)2. Furthermore, there were raised levels of alkaline phosphatase (315 U/l) and parathormone (1076 ng/l, normal: 10-65). X-ray film of the hands showed soft tissue and arterial calcifications, while histological examination of a deep skin biopsy revealed calcium phosphate emboli of the main vessels. TREATMENT AND COURSE: Excision of the cutaneous necroses was followed by parathyroidectomy at which only three parathyroid glands were identified and removed. The parathormone level fell postoperatively, but rose again after 4 weeks. The fourth parathyroid gland was then found and removed, after which the parathormone level fell below measurable levels. The skin ulcers healed completely 4 weeks after the second operation.

Calciphylaxis↗
PubMed1995

Mortality ascertainment in the veteran population: alternatives to the National Death Index.

Veterans of the US military service constitute a dynamic cohort that is suitable for epidemiologic investigations. However, the ability to ascertain vital status is paramount to the value of this population in studies having mortality as a primary endpoint. The purpose of this study was to estimate and compare the mortality ascertainment obtained from the Department of Veterans Affairs Patient Treatment File and Beneficiary Identification and Record Locator System (BIRLS) with that obtained from the National Death Index on a cohort of 17,118 male veterans hospitalized in 1970 or 1971. Based on the 4,246 deaths identified in this cohort between 1979 and 1988, the sensitivities of BIRLS, the Patient Treatment File, and the National Death Index were 94.5%, 33.0%, and 96.7%, respectively. BIRLS was comparable with the National Death Index regarding mortality ascertainment and allowed for central acquisition of 89% of the death certificates from the Department of Veterans Benefits. There was no difference detected in the completeness of the BIRLS file before and after passage of the Omnibus Act in 1981. The Patient Treatment File served as a complement to BIRLS, providing additional mortality data and identification of hospitals for recall of medical records. The National Death Index provided the best mortality ascertainment, but acquistion of death certificates from individual states was extremely time consuming and expensive. The authors recommend greater consideration by investigators of sampling the veteran population and utilizing available Veterans Affairs databases for large studies in which mortality is the primary endpoint of interest.

Adult↗
PubMed1995

A multivariate analysis of mental hospital recidivism.

This study identifies health problems, instrumental activities of daily living, employment status, and number of previous admissions as significant factors of recidivism to a mental health residential facility. The study, conducted over a 5-year period, includes measures on 32 predictor variables collected either on admission, on discharge, or 12-15 months following discharge or on readmission. The study's results are interpreted in light of current changes in the mental health service delivery system including the interactive role of physical and mental illnesses, expanding access to community-based generic services, focusing on functional skills and their development or remediation, and the changing criteria for measuring mental health effectiveness.

Catchment Area, Health↗
PubMed1995

[Reticular elastolytic giant cell granuloma. A variant of the annular elastolytic giant cell granuloma].

The case report presented describes a new variant of annular elastolytic giant cell granuloma. Over a period of 10 years, a 40-year-old woman had developed reticular, brown to livid, partly atrophic skin lesions on the shoulders and decolletée. The patient had no subjective symptoms. Histology revealed a patchy lymphohistiocytic infiltrate in the dermis, with many giant cells. Elastic fibres were less frequently found in these infiltrates; in a few of the giant cells and macrophages fragments of elastic fibres were demonstrated within the cytoplasm. There were no deposits of mucin. For this new variant we propose the term "reticular elastolytic giant cell granuloma."

Adult↗