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Biomedical subjects

T Urban

Publications and source records attributed to T Urban.

At least 55 records · Page 3Linked to original sources
PubMed1997

Neutrophil function and glutathione-peroxidase (GSH-px) activity in healthy individuals after treatment with N-acetyl-L-cysteine.

The objective of this study was to evaluate the effect of N-acetyl-L-cysteine (NAC) on neutrophilic functions and as an antioxidant. NAC, 600 mg daily, given orally to healthy individuals for a period of 2 weeks, affected some functions of human neutrophilic granulocytes when tested in vitro. NAC treatment caused a decrease in the production of superoxide anions by stimulated neutrophils and the improvement of their phagocytic capacity although it did not affect their random or chemotactic migration. The level of glutathione peroxidase (GSH-px) in thrombocytes of the NAC-treated individuals was increased in comparison with the activity before treatment. These results suggest that NAC might act as a scavenger of oxygen-derived free radicals released by stimulated neutrophils and thereby protect the tissue against the radical caused injury as well as optimize phagocytosis.

Acetylcysteine↗
PubMed1997

Ribavirin therapy for adenovirus pneumonia in an AIDS patient.

We report the effectiveness of ribavirin in an AIDS patient with multinodular pneumonia due to adenovirus. A 38-year-old AIDS patient who experienced multiple opportunistic infections and whose CD4 lymphocyte count was 5/mm3 developed bilateral nodular lung opacities. Lung surgical biopsy yielded necrotizing pneumonitis with characteristic nuclear inclusions and positive immunocytology with adenovirus antibodies. Marked clinical and radiological improvement was obtained after intravenous then oral ribavirin. Ribavirin was discontinued after 40 d because of anemia. Relapse of pneumonia with respiratory distress led to death 8 mo later. This observation illustrates a rarely reported pulmonary opportunistic infection in AIDS and the potential value of ribavirin therapy for adenovirus pneumonia.

AIDS-Related Opportunistic Infections↗
PubMed1997

MDR1-Pgp 170 expression in human bronchus.

MDR1 P-glycoprotein (Pgp 170), a member of the adenosine triphosphate (ATP) binding cassette transporters, acts as an efflux pump for various hydrophobic agents, particularly for xenobiotics such as benzo(a)pyrene. It has also been shown to regulate cell-volume activated chloride channels. Pgp 170 could, therefore, be of particular importance in cellular mechanisms of defence in the airways and in the control of mucus layer composition. For these reasons, we evaluated the precise localization of Pgp 170 in human adult airways. Fresh non-neoplastic bronchial specimens were collected from 33 patients (26 smokers, four exsmokers and three nonsmokers) who underwent surgery for lung carcinoma. The presence of MDR1 messenger ribonucleic acid (mRNA) was demonstrated by reverse transcriptase chain reaction (RT-PCR) in bronchial epithelial cells collected by gentle scraping from either smokers, exsmokers or nonsmokers. Immunodetection of Pgp 170 using a panel of monoclonal antibodies (MRK16, JSB1, C219, C494) was performed either on cryostat or paraffin-embedded sections of histologically normal bronchial tissue. Pgp 170 was constantly detected with intense labelling at the apical surface of ciliated epithelial cells from the surface epithelium or ciliated collecting ducts, and on apical and lateral surfaces of serous cells from bronchial glands. No staining of mucus-secreting cells was observed. Pgp 170 was also demonstrated at the luminal surface of endothelial cells of bronchial capillaries. In conclusion, the expression of MDR1 P-glycoprotein in bronchial structures, particularly at the epithelial apical surface, suggests important roles for this transmembrane protein in human airways.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1997

[A rare cause of Pierre Marie hypertrophic osteoarthropathy: subacute infectious endocarditis].

Secondary hypertrophic osteoarthropathy occurred in a patient with subacute endocarditis. Chest x-ray in this smoker with ethylic cirrhosis showed a pulmonary opacity. Clinical signs of osteoarthropathic inflammation resolved with antibiotics before surgical cure of the aortic insufficiency. The diagnosis was retained on the basis of outcome after antibiotic therapy and the absence of any other etiology, notably bronchogenic cancer. Endocarditis or infectious endarteritis should be entertained in case of hypertrophic osteoarthropathy in patients with an infectious syndrome. Pathogenic hypotheses are discussed. In congenital cardiopathies, intrapulmonary shunts, megacaryocytes and activation of the vascular-platelet endothelium unit may be involved. Bacterial factors and platelet aggregation could play a role in initiating hypertrophic osteoarthropathy in patients with infectious endocarditis.

Blood Platelets↗
PubMed1996

Efficacy and toxicity of mitomycin, ifosfamide, and cisplatin (MIP) in patients with inoperable non-small cell lung cancer.

Seventy-two patients with advanced stage IIIB (42%) or stage IV (58%) non-small cell lung cancer (median age 57 years, Karnofsky PS 60-100) were treated with mitomycin C (6 mg/m2, day 1), ifosfamide (1500 mg/m2, days 1-3), and cisplatin (30 mg/m2, days 1-3) every 4 weeks. The objective response rate was 37% in the overall population; 50% in stage IIIB patients and 29% in stage IV patients. Twenty four patients achieved partial response (33%) and three patients achieved complete response. Despite this relatively high objective response rate, the overall median survival time was 32 weeks. The median survival was significantly better in stage IIIB patients (55 weeks) than in stage IV patients (25 weeks) (P = 0.003). MIP regimen was permanently suspended in 14 patients because of toxic events. Seventeen patients developed grade III or IV febrile neutropenia and two patients died from sepsis. Two patients experienced acute mitomycin peumonitis. Despite increased doses of cisplatin and ifosfamide, compared with the original description for MIC chemotherapy, with probably higher toxicity, no apparent increased response rate or median survival was observed in this study. The MIP regimen could be tested in a randomized trial in comparison with other administration plans in a comparable population.

Adult↗
PubMed1996

Codon 12 Ki-ras mutation in non-small-cell lung cancer: comparative evaluation in tumoural and non-tumoural lung.

Ki-ras activation by point mutation on codon 12 has been reported in non-small-cell lung carcinomas and in various models of experimental lung tumours induced by chemical carcinogens. The cellular targets for carcinogenic compounds of tobacco smoke are usually considered to be the cells of the bronchial mucosa or alveolar epithelium. However, little is known about preneoplastic events in bronchopulmonary carcinogenesis. The hypothesis of the presence of widespread target cells containing Ki-ras mutation was investigated by evaluating concurrent neoplastic and non-neoplastic bronchial and alveolar samples from 51 patients with non-small-cell lung carcinomas. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method used can detect one cell with a mutation on codon 12 among 10(2) normal cells. In tumour samples, a mutation was detected in 20% of adenocarcinomas, but in none of the adenosquamous or squamous cell carcinomas. No mutation was detected in the non-neoplastic bronchial or parenchymal samples. When using an enriched PCR-RFLP method detecting one mutated allele among 10(3) normal alleles a mutation was detected in 23% of adenocarcinomas. In conclusion, Ki-ras activation by mutation on codon 12 was not observed in non-neoplastic bronchial or parenchymal tissues in patients with bronchopulmonary cancers and does not appear to be a genetic event present in non-malignant epithelial target cells exposed to tobacco smoke.

Carcinoma, Non-Small-Cell Lung↗
PubMed1996

Colony-stimulating factors as an adjunct to chemotherapy in small cell lung cancer.

Myelosuppression is the major dose-limiting toxicity of chemotherapy in small cell lung cancer (SCLC). The capacity of colony stimulating factors (CSFs) to stimulate granular neutrophil recovery may be of great value to prevent or cure febrile neutropenia and to increase dose-intensity. The aim of this review was to assess the current use of CSFs in SCLC on the basis of experimental and clinical data. Primary CSF administration has been shown to reduce the incidence of febrile neutropenia, hospital admission rate, and antibiotic use subsequent to cyclophosphamidedoxorubicin-high dose etoposide (CDE) chemotherapy, without improvement of survival or disease control. Primary CSF administration may be recommended when the expected incidence of febrile neutropenia is at least 40%. This benefit has not been established with less myelosuppressive regimens, such as cisplatin-etoposide (PE), which remains an alternative combination of SCLC when standard doses are used. A trial comparing high-dose CDE + CSF with PE would be of considerable interest. There is currently little clinical basis for the use of CSFs to increase chemotherapy dose-intensity, outside clinical trials. Peripheral blood progenitor cells mobilized with CSFs offer interesting prospects. Further studies, with later initiation, shorter duration or lower doses of CSFs, are warranted to improve the cost-effectiveness of CSFs. CSF therapy in addition to antibiotics is normally not justified in febrile neutropenia, except perhaps in selected patients with sepsis syndromes, hypotension or pneumonia.

Antineoplastic Agents↗
PubMed1996

[Rupture of the flexor tendon of the hand caused by tuberculosis].

A 47 years-old man presented an atraumatic, spontaneous index flexor tendons rupture. This patient has been treated two years ago for a pulmonary tuberculosis. At surgery, the flexor tendons were infiltrated by a granuloma. Histologic examination was compatible with tuberculosis sequelae. According to literature review, this is the second reported case of a tendon rupture due to tuberculosis granuloma.

Follow-Up Studies↗
PubMed1995

[Pulmonary lymphangiomyomatosis. Long-term benefit of anti-estrogen treatments remains uncertain].

Lymphangiomyomatosis is a rare disease which affects young women of childbearing age. Ten women with pulmonary lymphangiomyomatosis were treated with antiestrogen therapy from 3 to 9 years (mean time of treatment: 5.3 years). Efficacy of treatment was evaluated by clinical, radiological, pulmonary function testing response as well as the overall long-term outcome. Four patients died of respiratory failure after 3, 5, 5 and 9 years of treatment. Of the 6 patients remaining alive, respiratory function deteriorated in 4 cases after a transient period of mild improvement lasting 3 years in 2 cases. Two patients appeared stable after 3 and 7 years of treatment. Without a control group, although a longer time of survival along these last years, it seems difficult to impute this benefit to the sole antiestrogen treatment and the overall long term prognosis of the disease remains really uncertain.

Adult↗
PubMed1995

[Oxidants and antioxidants. Biological effects and therapeutic perspectives].

The main oxidizing free radicals (FR) are oxygen-derived metabolites (superoxide anion O2-, hydrogen peroxide H2O2, hydroxyl radical OH (zero)), hypochloric acid, chloramines, nitrogen dioxide, ozone and lipid peroxides. They are produced continually by living organisms, either in the intracellular compartment by the mitochondrial respiratory chain and mixed function oxidase system, or in the extracellular compartment, especially by phagocytes. The body possesses complex protective antioxidant systems against this potentially toxic production, such as dismutase superoxides, catalase, the glutathione enzyme system, metallic ion sequestration, enzymes degrading proteins injured by FR, metabolising hydroperoxides, and repairing DNA, and vitamins E, C, P, and betacarotene. A physiological steady-state is established under normal conditions between the production of oxidants and their neutralization by antioxidants. Oxidative lesions result from a disturbance of the oxidant-antioxidant balance. Oxygen-derived metabolites act on polyunsaturated cell membrane lipids, induce genetic alterations, and oxidize sulfhydryl groups of proteins, thereby modifying their functions. FR are involved in major physiological mechanisms such as phagocytosis, the inflammatory reaction, and the reperfusion ischaemia phenomenon observed during organ storage. The therapeutic use of enzymatic (SOD, catalase, GSH) and nonenzymatic antioxidants (vitamins E, N-acetylcysteine, allopurinol and oxypurinol) has yet to be evaluated. The current state of our knowledge indicates the extreme complexity of these systems and calls for caution in the therapeutic use of antioxidant substances.

Antidotes↗
PubMed1995

[Allopurinol hypersensitivity. A possible cause of hepatitis and mucocutaneous eruptions in a patient undergoing antitubercular treatment].

The authors describe a case of drug-induced cytolytic hepatitis probably secondary to hypersensitivity to allopurinol which was prescribed incorrectly for secondary hyperuricaemia during treatment with pyrazinamide. The diagnosis was reviewed in view of the late occurrence of hepatitis in relation to the onset of the antituberculous treatment, the absence of a viral aetiology and the presence of clinical manifestations, biological and histological features which were compatible with hypersensitivity to allopurinol. The authors recalled that the type of uricaemia induced by pyrazinamide is most often asymptomatic and does not require any treatment with uric acid lowering drugs. Cessation of pyrazinamide is justified in cases of symptomatic hyperuricaemia but when the indications for pyrazinamide are imperative, treatment with an eliminator of uric acid is indicated. Allopurinol is contra-indicated in association with pyrazinamide on account of its inhibitory reaction to xanthine oxidase. Xanthine oxidase decreases the level pyrazinoic acid, a metabolite of pyrazinamide, which is responsible for the inhibition of the tubular secretion of uric acid.

Adult↗
PubMed1995

[Total hip replacement without blood transfusion].

Total hip replacement has been performed in 32 patients. On the basis of investigation conducted it has been demonstrated, that 70 per cent of operated patients did not require blood transfusion taking contemporary indications for hemotherapy into consideration. A modified intraoperative and postoperative management is necessary, however.

Aged↗
PubMed1994

[Antioxidant minerals and vitamins. Role in cancer prevention].

Cancer is a disease of the genome and free-radicals can damage genomic DNA, hence the interest in the potential protective antioxidant effect of vitamin and minerals. Indeed, the findings of most retrospective studies suggest that diets rich in fruits and vegetables have a protective effect against cancer. Prospective randomized trials have however given controversial results. Beta-carotene, the precursor of vitamin A has been shown to induce regression of precancerous lesions and 13-cis retinoic acid has a preventive effect on the development of a second cancer in patients with epidermoid cancer of the buccal cavity, the pharynx or the larynx although no effect has been observed on the primary cancer. Current research also suggests vitamin C has a potential anticancer effect, particularly for cancer of the stomach, the rectum and the cervix. For vitamin E, epidemiological data give less conclusive results. Several prospective studies suggest the absence of any correlation between vitamin E intake and general risk of cancer. A Chinese trial has shown a decreased incidence of oesophageal and gastric carcinoma while a Finnish trial revealed increased incidence of cancer among smokers treated by beta-carotene and vitamin E. Selenium and zinc intake, based on geographical correlations, has also been suggested to affect cancer incidence, but the results of prospective studies are conflicting. For example in 10 such trials analyzing blood selenium levels and risk of cancer, 4 have demonstrated a significant correlation. Further research is needed but is hindered by the absence of an adequate animal model and the difficulty in conducting large clinical trials. Nevertheless, positive data collected to date must be validated to determine the real effect of dietary preventive measures in the fight against cancer.

Animals↗
PubMed1993

Detection of c-Ki-ras mutation by PCR/RFLP analysis and diagnosis of pancreatic adenocarcinomas.

BACKGROUND: The c-Ki-ras oncogene (also known as KRAS2) is activated by point mutations involving codon 12 in 72%-100% of primary pancreatic adenocarcinomas, but the gene is not activated in nonneoplastic tissues. Therefore, the detection of c-Ki-ras mutations can facilitate the diagnosis of pancreatic adenocarcinomas, which are not always identified with current tests. Detection is usually performed by oligonucleotide hybridization combined with polymerase chain reaction (PCR), RNAse mismatch cleavage assay, or non-isotopic mismatched PCR, methods that are not feasible for routine screening of large numbers of samples because they are time consuming and/or expensive. PURPOSE: Our purpose was to evaluate a rapid, non-radioactive method of detection of a mutation in codon 12 of the c-Ki-ras gene in pancreatic tumor samples obtained by fine-needle aspiration for diagnostic screening. METHODS: Twenty consecutive patients (15 with pancreatic adenocarcinoma, one with pancreatic cystadenocarcinoma, one with endocrine islet cell tumor, and three with chronic pancreatitis) were selected for this study. A sample of pancreatic tissue from each patient with a tumor or pancreatitis was obtained and evaluated by fine-needle aspiration biopsy under computerized tomography scan or ultrasound guidance using a two-needle coaxial technique. Pancreatic DNA from each of these samples was evaluated by PCR amplification and restriction fragment length polymorphism (RFLP) analysis with nucleotide substitution in PCR primers, creating BstNI restriction patterns that distinguished mutated from normal alleles. The accuracy of the PCR/RFLP assay was validated with DNA from SW480 and HT29 colonic carcinoma cell lines with known mutated and wild-type c-Ki-ras gene sequences. Sensitivity was tested with a series of titration experiments. RESULTS: PCR/RFLP analysis can detect a mutation present in 1% of cells. No amplification could be performed in four (20%) samples because of the absence of cells in the aspirated sample. In the 16 samples adequate for PCR/RFLP analysis, a c-Ki-ras gene mutation was detected in 11 (92%) of 12 adenocarcinomas. Overall, diagnosis was obtained by pathologic (cytomorphologic) examination alone in 13 samples (81%). The presence of malignant cells and/or mutated c-Ki-ras gene was detected in 12 of 12 adenocarcinomas but not in chronic pancreatitis or islet cell tumor. CONCLUSION: Screening of pancreatic tissue samples obtained by fine-needle aspiration for c-Ki-ras mutation using PCR/RFLP analysis combined with pathologic examination could facilitate diagnosis of pancreatic tumors.

Adenocarcinoma↗
PubMed1993

Superior vena cava syndrome in small-cell lung cancer.

BACKGROUND: The aim of this study was to analyze the features of the superior vena cava syndrome (SVCS) as initial characteristics in small-cell lung cancer: incidence, dissemination of disease, diagnostic procedures, efficacy and toxic effects of chemotherapy, and median survival in patients with SVCS. METHODS: In a prospective series of 724 patients with biopsy-proved small-cell lung cancer seen during a 6-year period, we reviewed data from patients who also had SVCS. RESULTS: The incidence of SVCS was 87 of 724 at the time of diagnosis. Initial emergency radiation therapy was not used in these patients. Diagnostic procedures in these patients were not associated with mortality. Rapid initiation of intensive chemotherapy, often with heparin therapy, resulted in complete or partial responses in 81% and no response in 12%; data were not evaluable in 7%. Two of these 87 patients died of aplasia within 4 weeks of chemotherapy. Median survival was not significantly different in the patients with SVCS (median, 42 weeks) and without SVCS (median, 40 weeks). A significant increase in initial brain metastases at the time of diagnosis was observed in patients with SVCS (22% vs 11%). CONCLUSIONS: Intensive chemotherapy is the first line of therapy in small-cell lung cancer. Histologic diagnostic procedures must be performed in patients with SVCS to adapt the treatment to the underlying cause. Initial emergency radiotherapy, before diagnosis or chemotherapy, does not seem to be useful in these patients. Computed tomography of the brain should be performed routinely in patients with SVCS, and prophylactic brain irradiation could be helpful in such patients. Apparently SVCS is not a poor prognostic factor in treated small-cell lung cancer.

Adult↗
PubMed1993

[Consequences of specific prevention on the diagnosis of Pneumocystis carinii pneumonia in patients with HIV infection. Comité SIDA de l'Hôpital Saint-Antoine].

In a prospective study the authors compared the clinical, radiological, biochemical and diagnostic features of Pneumocystis carinii pneumonia (PCP) in HIV-infected patients who were or were not receiving a specific prophylactic treatment. The study included 386 patients with suspected PCP, 201 of whom were under specific prophylactic therapy. Induced expectoration and/or bronchoalveolar lavage provided a diagnosis of PCP in 89 patients, 21 of whom were under specific prophylaxis. Apart from a number of circulating CD4 lymphocytes that was significantly lower in the patients under prophylaxis, there was no significant difference between the two groups. Thus, being under specific prophylaxis should have no effect on the diagnosis of PCP in HIV-infected patients.

AIDS-Related Opportunistic Infections↗