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Biomedical subjects

A Cattan

Publications and source records attributed to A Cattan.

At least 19 recordsLinked to original sources

Glutathione S-transferase activity and isoenzyme distribution in ovarian tumour biopsies taken before or after cytotoxic chemotherapy.

A study involving the measurement of glutathione S-transferase activities and isoenzyme distributions in human ovarian tumours has been carried out. These tumours have been obtained either at initial debulking surgery, prior to cytotoxic chemotherapy, or at second look laparotomy following chemotherapy. The response rates of these two groups to chemotherapy differ markedly, with patients who have relapsed following initial chemotherapy showing a reduction in response rates to subsequent chemotherapy. Analysis of these data show no statistically significant differences between the glutathione S-transferase activity or isoenzyme distribution in these two groups of patients. Significant differences were observed in the glutathione-S-transferase activities (GST) between tumours and normal ovaries. GST activities in pre-chemotherapy tumours (n = 33, P = 0.01) and post-chemotherapy tumours (n = 20, P = 0.001) where significantly higher than the GST activity in normal ovaries (n = 15). One feature was the expression of the basic isoenzyme which is expressed more in normal ovaries than in tumours. No differences in these parameters were observed in normal peritoneal tissue taken from patients before or after chemotherapy. These data do not support the hypothesis that changes in glutathione S-transferase enzyme activity or isoenzyme expression are major determinants of response to chemotherapy in ovarian tumours.

Adult

Correlation of clinical pharmacokinetic parameters of cisplatin with efficacy and toxicity.

Twenty-two pharmacokinetic studies were carried out in 11 patients receiving cisplatin (20 mg/m2 per d) associated with etoposide (50 mg/m2 per d), as 5-day continuous infusions, every 4 weeks. Blood was withdrawn at 8:30 am from day 1-5. Within 15 min after taking the blood, an aliquot of plasma was filtered for the ultrafilterable platinum (UP) assay. Total platinum (TP) and UP were assayed by flameless atomic absorption. The plasma concentrations and AUC0-120 h of TP were correlated with those of UP (P less than 0.05 to P less than 0.001). TP concentrations increased significantly during the infusion and with each successive course, whereas the increase of plasma concentration of UP during and between courses was not statistically significant. The responders had significantly higher levels of TP (AUC, concentrations) in the first and second courses than the non-responders. No renal toxicity was observed, nevertheless, the AUC0-120 h of TP and UP were positively correlated with the serum creatinine (P less than 0.05). The digestive intolerance (grade 1-3) was significantly correlated with TP concentrations and AUC0-120 h. There was no statistical difference in UP concentrations either between responders and non-responders in any course, nor between toxic and non-toxic courses. Since etoposide was concomitantly administered, we can formulate the conclusion as follows: no "objective" response was observed in the patients with low TP plasma concentrations and AUC0-120 h.

Cisplatin

Pirarubicin in advanced breast cancer: a French cooperative phase II study.

79 patients with advanced breast cancer were given Pirarubicin 20-25 mg/m2 during 3 consecutive days every 3 or 4 weeks. 78 were evaluable for response (41 without previous chemotherapy and 37 with only one previous regimen). The overall response rate was 35% (95% CI 24-45) and the complete response rate was 8%. In previously untreated patients, the response rate reached 41.5%. The limiting toxicity was a non-cumulative granulocystopenia, sometimes severe at these high doses, with a prompt recovery. The non-haematological toxicities were mild, and included 13% with grade 3 alopecia.

Adult

Discriminating between protective and enhancing HIV antibodies.

Most attempts to produce a vaccine against HIV-1 infection are utilizing envelope protein components. Hypothetically such vaccine candidates could stimulate production of antibodies that enhance HIV-1 infection via the macrophage route of entry and, consequently, cannot be detected in the conventional neutralization assay. To study this hypothesis we report an assay designed to evaluate the protective/enhancing activity of serum from seropositive immunized or infected individuals. Highly purified activated FcR-bearing monocytes-macrophages were infected with HIV-1 in the presence of the sera, then washed and cocultured with activated peripheral blood mononuclear cells (PBMC) from a normal donor. Productive viral infection, as evaluated by p24 antigen semiquantitative assay in the culture supernatants, allow evaluation of protective/enhancing activity of the sera. The data clearly show that protective rather than enhancing activity is present in the serum of env protein-immunized individuals.

Acquired Immunodeficiency Syndrome

Five-day continuous infusion of cisplatin and etoposide in non-small cell lung cancer. A phase II trial.

Cisplatin (CDDP) and etoposide are synergistic in vitro: the aim of this study was to evaluate the efficacy of a continuous infusion (C.I.) of these 2 drugs in inoperable non-small cell lung cancer. Patients were to receive 3 courses of CDDP 20 mg/m2/d in 1 l saline x 5d and etoposide 50 mg/m2/d in 21 saline x 5d--both in C.I.--every 3-4 weeks. Thirty patients have entered the study. Four were inevaluable for response. One patient got complete remission, 15 partial remission, 8 no change and 2 progressive disease. The response rate was 53.3% overall (95% confidence interval: 35-71%), and 61.5% for 26 assessable patients. Toxicity appeared to be acceptable despite 52% transient neutropenia--one patient died during aplasia--and 78% grade 1 to 3 nausea or vomiting. Treatment was stopped in only one case, and modified in 6 others. The high response rate that we observed, supports the idea of potentiation of the antineoplastic effect of CDDP and etoposide by C.I., in non-small cell lung cancer. These results must be confirmed in larger series before definitive conclusions can be drawn.

Adult

Serum levels of CA-50, CA-19.9, CA-125, neuron specific enolase and carcinoembryonic antigen in lung cancer and benign diseases of the lung.

The serum levels of five markers (CA-50, CA-19.9, CA-125, Enolase (NSE) carcinoembryonic antigen (CEA) were studied in 96 lung cancer patients and in 60 patients with benign diseases of the lung: sensitivity was 0.44, 0.41, 0.54, 0.23 and 0.38 respectively; specificity was 0.67, 0.87, 0.47, 0.93 and 0.97 respectively. Serum levels of CA-125 over 20 U/ml were found in 74% of patients with acute pneumonia. A good parallel existed between the clinical evolution of lung cancer and the variations in the serum level of CA-50, CA-19.9 and NSE. Although the pretreatment result was elevated, successive assays of the marker allowed the clinical evolution to be followed. Conflicting results were found with CA-125 and to a lesser extent with CEA. A close correlation existed between the serum levels CA-50 and CA-19.9 in the 2 groups of patients. In the absence of a specific marker for lung cancer, complementary information can be provided by means of a simultaneous determination of CEA, NSE, CA-19.9--or CA-50--and CA-125.

Adolescent

[CA-125 in non-ovarian benign and malignant pathology: study on 380 patients].

CA-125, a serum marker of epithelial ovarian cancer, was studied by a radioimmunometric method: the sensitivity and specificity of the assay was studied in 260 patients with non ovarian carcinomas and 120 patients with non malignant diseases. The ideal threshold value has been discussed. Levels higher than 20 UI/ml (cut-off value) have been found in 53% of cases. Sensitivity falls to 25% if the cut-off value is 65 UI/ml. The serum levels correlated well with the existence of a metastatic disease (P less than 0.001). A second assay allowed to study in 163 cases the correlation between the variations of the serum level and the clinical evolution; a good correlation was found except in case of stable disease. High levels have also been found in patients with benign diseases, most of all in cases of pneumonia and severe liver cirrhosis.

Adolescent

Results of a five-drug combination chemotherapy in non-small cell lung cancer. A phase II trial.

Twenty-six non-small lung cancer patients entered a phase II trial of a 5-drug combination chemotherapy. On day 1, patients received vinblastine, bleomycin, methotrexate, 5-FU, cisplantinum, leucovorin, and a similar sequence with an increased dosage was administered on day 6. Out of 22 fully evaluable patients we observed 1 CR and 7 PR. Hematological toxicity was significant, including 15 cases of neutropenia grade 4 and four grade 3, with one death during aplasia. Our results are disappointing but they are similar to most current reports on drug combinations in advanced non-small cell lung cancer. A better scheduling might improve the efficiency toxicity ratio.

Adult

A new approach to image subtraction in immunoscintigraphy: preliminary results.

Recently proposed image comparison software is applied to immunoscintigraphy. The software performs geometric and gray level registration of two images and generates an image of the statistically significant differences. It permits the comparison of scintigraphic images recorded at different times. It is used to subtract 113mIn and 111Inphytate colloid liver scans and early (blood pool) images from 131I or 111In-monoclonal Ab images and to compare Ab images recorded at different times. Using the procedures made possible by this software, only images recorded using the same radionuclide or using radionuclides of about the same energy are compared. Anti CEA, 19-9 and OC 125 F(ab)2 fragments labeled with 131I or 111In are used in 32 patients with 47 demonstrated recurrences or metastases of colorectal or ovarian cancers. The overall sensitivities of the unprocessed and processed images are 25/47 and 41/47 respectively. The improvement in sensitivity is particularly high in the liver when In labelled Ab are used. This technique improves the contrast of the images, but the interpretation must take into account the components of the non target activity (kidney, bone marrow, colon...) which are not removed by the image subtraction method.

Antibodies, Monoclonal

[Comparative analysis of serum levels of CA-50, CA-125, CA-19.9, enolase and CEA in bronchopulmonary cancer].

A serum assay of CA-50, CA-125, CA-19.9, ENOLASE (NSE) and CEA was performed in 65 patients with primary lung cancer, 63% of whom had visceral metastases, with the following histological distribution: squamous carcinoma (40), adenocarcinoma (9), large cell carcinoma (4), oat cell carcinoma (12). A raised CEA level was detected in 37% of cases, compared with 40.6% for CA-50, 44.6% for CA-19.9 and 40.6% for CA-125 and only 26.6% for NSE. Overall, at least one marker was positive in 83% of cases. Statistical analysis of the different markers (correlation analysis and principal component analysis) demonstrated the existence of a strict correlation between the levels of CA-50, CEA and CA-19.9 (p less than 0.01). ENOLASE was more frequently elevated in oat cell carcinomas (42%) than in non-oat cell carcinomas (30%), but the difference was not significant. In contrast, CA-125 appears to be a good marker for non-oat cell carcinomas (51%) (p less than 0.05). The authors also found a correlation between the presence of a raised level of CA-50 (p less than 0.05), CA-125 (p less than 0.02) and especially CEA (p less than 0.001) and the presence of visceral metastases. The initial survey of disseminated lung cancers should include the assay of at least 4 of these markers in order to obtain a reliable serum tracer in more than 2/3 of cases.

Adenocarcinoma

Evidence for HTLV-III in T-cells from semen of AIDS patients: expression in primary cell culture, long-term mitogen-stimulated cell cultures, and cocultures with a permissive T-cell line.

The development of acquired immunodeficiency syndrome or of acquired immunodeficiency syndrome-related complex by transmission of human T-lymphotropic retrovirus III by semen has previously been implicated by epidemiological studies. In vitro investigations were performed on mononuclear cells obtained from the semen of patients with acquired immunodeficiency syndrome to identify human T-lymphotropic retrovirus III or related retrovirus. The presence of human T-lymphotropic retrovirus III was demonstrated (a) in primary cell cultures, by the detection of the Mr 24,000 protein by indirect immunofluorescence assays by Day 6; (b) in activated long-term cell culture by reverse transcriptase activity, by indirect immunofluorescence (Mr 24,000 protein); and (c) in cocultures of T-cells from semen of AIDS patients and H9 cells by reverse transcriptase activity, indirect immunofluorescence, and the presence of virus particles by electron microscopy.

Acquired Immunodeficiency Syndrome

[Cutaneous localization of Hodgkin's disease. Description of 4 cases and review of the literature].

Cutaneous involvement is uncommon in Hodgkin disease. Among 167 Hodgkin patients, we observed skin lesions in four. Clinical and histopathological features are discussed and compared with those of 40 other well-documented cases previously reported in the literature. The wide spectrum of clinical patterns and variability of outcome are underlined. Skin biopsy is mandatory and provides cardinal evidence for diagnosis; however, the Reed Sternberg cell is not absolutely specific and caution must be taken in affirming a disease which implies major therapy. In most observations, skin involvement obviously has no bearing on prognosis. We believe that the reality of specific Hodgkin skin lesions is subject to major reservations.

Adult