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Biomedical subjects

V Wiebe

Publications and source records attributed to V Wiebe.

At least 37 records · Page 2Linked to original sources

[The importance of 201-thallium myocardial scintigraphy in the hypertensive patient].

Thallium-201 exercise myocardial scintigraphy was performed in 57 patients (37 males, 20 females; mean age 55.4 [43-78] years) with angina and systemic hypertension after exclusion by coronary angiography of any coronary macroangiopathy. The exercise ECG of 32 patients could not be used in the diagnosis of ischaemia because of the presence of left ventricular hypertrophy with abnormal repolarization or left bundle branch block. Abnormal haemodynamics were demonstrated at cardiac catheterization in 23 patients (Swan-Ganz). Only 10 of the studied hypertensives with normal coronary angiograms had a myocardial scintigram within normal limits, while 12 had extensive ischaemic zones in the left ventricle. All patients with left bundle branch block had evidence of exercise-dependent apical "ischaemia". Thallium-201 myocardial scintigraphy should not be used as a screening method in hypertensives with angina, because the high proportion of "false-positive" findings, in the sense of a macroangiopathy, will nevertheless require early invasive diagnosis.

Adult↗

Toremifene and its metabolites enhance doxorubicin accumulation in estrogen receptor negative multidrug resistant human breast cancer cells.

The enhanced accumulation of doxorubicin by agents known to reverse multidrug resistance provides a good functional test for evaluating modulating activity. In the present study, the non-steroidal triphenylethylene toremifene selectively increased doxorubicin accumulation in multidrug resistant estrogen receptor negative MDA A-1 human breast cells compared to the MDA 231 wild type cells. MDA A-1 cells were noted to be 1,000 fold resistant to doxorubicin (IC 50 = less than 0.1 microgram/ml MDA 231; IC 50 = 100 micrograms/ml MDA A-1). Total accumulation of doxorubicin, expressed as area under the time concentration curve (AUC), was increased significantly in doxorubicin resistant cells (156% increase) versus wild type MDA 231 cells (6% increase). Correction of the accumulation defect to doxorubicin in drug resistant cells required a 18-20 hour pre-incubation with toremifene. The effects of toremifene on cell cycle in MDA A-1 cells was analyzed by flow cytometric techniques. Toremifene had a dose response relationship in blocking cells in G0-G1 reducing the number of cells entering S phase of the cell cycle. This effect was maximal at concentrations which increased the accumulation of doxorubicin in MDA A-1 cells. Several metabolites of toremifene were also noted to increase doxorubicin accumulation in MDA A-1 doxorubicin resistant cells. Tore XVIII (deaminocarboxytoremifene), Tore IV (4-hydroxy-N-desmethyltoremifene) and N-desmethyltoremifene all increased the accumulation of doxorubicin significantly (114%, 128% and 42% respectively). Finally, we show evidence that toremifene and its active metabolites are present in high concentrations in human plasma following a single 200 mg oral dose.(ABSTRACT TRUNCATED AT 250 WORDS)

Antineoplastic Agents↗

A bioassay for antiestrogenic activity--potential utility in drug development and monitoring effective in vivo dosing.

Monitoring effective antiestrogenic activity of the triphenylethylenes in patients with breast cancer is usually determined by the duration of response. The pharmacokinetics of toremifene and tamoxifen have been shown to be highly variable but patient specific. In the present study, we developed a method to accurately assess the antiestrogenic activity of these agents using plasma specimens, cell culture, and cell cycle measurements. Plasma specimens (4-5mls) obtained from patients receiving toremifene (360mg/day for 5 days in a phase I trial) or tamoxifen (20mg/day) were extracted and reconstituted in tissue culture media (4-5mls), and growth inhibition was determined in estrogen responsive MCF-7 cells. Additionally, plasma specimens were quantified for toremifene or tamoxifen concentrations using HPLC. Growth inhibition of plasma specimens containing either toremifene or tamoxifen and their metabolites was also examined. Cell cycle measurements were determined following in vitro exposure with flow cytometric techniques. Our results show that a dose-response relationship exists between cell growth inhibition and cell cycle measurements for human plasma with added toremifene or tamoxifen, and also for human plasma specimens containing drug and its metabolites after treatment. Our antiestrogenic bioassay can address clinical research problems such as patient-specific pharmacokinetics, dosing compliance, and acquired antiestrogen resistance.

Breast Neoplasms↗

Acquired tamoxifen resistance: correlation with reduced breast tumor levels of tamoxifen and isomerization of trans-4-hydroxytamoxifen.

Acquired tamoxifen resistance represents a major cause of treatment failure in breast cancer. We implanted estrogen receptor-positive MCF-7 human breast cancer cells in athymic nude BALB/c mice as a model to study in vivo acquired tamoxifen resistance. After 4-6 months of tumor growth suppression by trans-tamoxifen, tumor progression was observed despite continued tamoxifen administration. Acquired resistance was not due to loss of estrogen receptors, to alterations in serum or tumor estrogen levels, or to changes in tamoxifen or its major metabolites in serum. Tamoxifen-resistant tumors remained estrogen dependent in vivo. However, resistance was also associated with the ability of tamoxifen to stimulate tumor growth. Resistant tumors were characterized by markedly lower intracellular tamoxifen levels and by isomerization of the potent antiestrogenic metabolite trans-4-hydroxy-tamoxifen to the less potent cis isomer. Metabolic tolerance, as manifested by alterations in cellular concentrations of tamoxifen and its metabolites, may thus be one mechanism for acquired tamoxifen resistance in breast cancer.

Animals↗

[Circumscribed venous ectasia of the upper esophagus and "downhill" varices in primary disorders of esophageal motility].

Felson and Lessure 1964 (1) described varicosities involving the upper third of the esophagus in patients without portal hypertension. Several etiological factors causing these "downhill" varices, e.g. bronchogenic carcinoma, retrosternal thyroid adenoma or mediastinal fibrosis, have been described. Since September 1989 ectatic esophageal veins or "downhill" varices were diagnosed in nine patients with dysphagia and/or non cardiac chest pain. Intrathoracic masses as a possible cause of "downhill" varices could not be diagnosed in any of these patients. Endoscopy of the upper gastro-intestinal tract revealed spiral esophageal contractions as a potential sign of a esophageal motor disorder in seven patients. By means of esophageal manometry "nutcracker"-esophagus was seen in two patients and diffuse esophageal spasm in three patients. On the basis of these findings primary esophageal motor disorders should be considered as a possible cause of ectatic veins in the proximal esophagus and "downhill" varices.

Aged↗

[Strut fracture of a convex-concave 60 degree Björk-Shiley mitral valve prosthesis 5 years after implantation--metallurgic analysis of the prosthesis strut].

Acute mechanical failure of prosthetic heart valves is rare, but associated with high mortality when occurring. For convexo-concave Björk-Shiley prostheses only fractures of the outlet strut are reported. We present a case of lethal mechanical complication 5 years after implantation. By additional metallurgic analysis we were able to identify a sequential course of the outlet strut fracture. This could lead to new approaches for early detection of this complication.

Adult↗

[Changes in the pleura of subjects occupationally-exposed to asbestos: radiological study technique, spectrum, etiological classification and coding according to the ILO classification].

Pleural abnormalities of 119 occupationally asbestos-exposed with prominent internal stripe of the lateral thoracic wall were radiodiagnostically analysed by plain films of the thorax in four views and by computed tomography in the course of medical expert's certification. Abnormalities were coded according to 1980 ILO international classification of pneumoconioses. Hardly half of the patients had pleural abnormalities caused by asbestos exposure: Pleural plaques, "diffuse" pleural fibrosis, pleural effusions, organized pleural effusions and pleural tumors. The other half of the patients had pleural involvement of pulmonary and chest wall abnormalities or variations of the lateral thoracic wall not related to asbestos exposure. The 1980 ILO classification of pneumoconioses proved to be inadequate for complete coding of the abnormalities, since only the postero-anterior plain film of the thorax must be used, since the normal appearance of the pleura is insufficiently defined and since the entity of organized pleural effusion is lacking.

Asbestosis↗

[Myxoid schwannoma of the forearm. A case report].

Tumors arising from or located within a peripheral nerve are not common and recognition and treatment are difficult. We report a patient with a myxoid swannoma surrounding the axon of ulnar nerve. This 50-year old woman had pain and tenderness. Careful clinical and technical investigation--including CT and angiography--could not give a definite diagnosis preoperatively. The patient was cured by simple enucleation without damage to the axon bundles. At surgery the appearance of the tumor was typical. An oval, encapsulated mass measuring up to 5.5 by 9 centimeters in diameter was seen. Only biopsy and pathologic examination can exclude malignancy. After follow-up of 48 months no local recurrence of the tumor was found.

Female↗

[Radiologic diagnosis of pneumoconioses].

Radiology is extremely important in the diagnosis of occupational lung disease. Owing to its general availability and international comparability, the roentgenographic pa view of the chest obtained by the high-voltage technique is still the basis of the radiologic examination. Supplementary investigations are necessary for medical reasons, however, as well as for documentation of experts' certification. Valuable diagnostic information is supplied by oblique views of the thorax and by conventional X-ray tomography, though not by scintigraphic examinations or - up to now - by digital luminescence radiography. Ultrasound helps in the differentiation of free pleural fluid, organized pleural effusion, and pleural malignancy. In addition, computed tomography (CT) can be guided by ultrasound. CT has emerged as the method of choice for examination and for support of medical experts' certification of pneumoconiotic pleural disease, and high-resolution CT (HRCT) is also increasing used for examination of pneumoconiotic lung foci as well. Diagnostic accuracy in pneumoconiosis is further improved by shorter CT scanning times in combination with HRCT.

Asbestosis↗

[Mucoviscidosis: late diagnosis despite typical clinical features].

An 18-year-old girl was hospitalized because of a treatment-refractory broncho-pneumonia requiring artificial ventilation. She had been suffering from recurrent respiratory infection since the age of three years. Chest X-ray films demonstrated bronchiectasis: Pseudomonas, Klebsiella and Candida albicans were isolated from the respiratory tract. The correct diagnosis of the underlying disease had not previously been made. A sweat test, when aged 15 years, was borderline abnormal. Despite the application of all available therapeutic measures she died in cardiorespiratory failure from an overwhelming pulmonary infection. The typical clinical features and the findings at autopsy established the diagnosis of mucoviscidosis.

Adolescent↗

[Arteriographic features of rare skin complications of chronic osteomyelitis].

In the period between 1970 and 1982, 6 carcinomas in scar tissue and 2 pseudocarcinomatous skin papillomatosis were found on the basis of chronic osteomyelitides. Amputation specimens of two carcinomas and one papillomatosis were examined by arteriography. Macroscopically carcinomas in scar tissue showed an unspecific appearance and microscopically a scarefied and partly pathological vascular appearance. Pseudocarcinomatous skin papillomatosis was distinctly hypervascular. Therefore, indications with regard to the localisation of an required exploratory excision can only be obtained from the vascular appearance of papillomatosis but not in case of a scar tissue carcinoma after osteomyelitis. Due to the overall bad blood circulation osteomyelitic scar tissue carcinoma scarcely reacts positively to a chemotherapeutic treatment.

Aged↗