Treatment of lead poisoning with unithiol in chronic renal failure.
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Biomedical subjects
Publications and source records attributed to C Lagarde.
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The incidence of zoster in 717 patients with Hodgkin's disease was determined by a retrospective chart review. All patients had been treated and followed in one of six cancer centers. Prognostic factors that might predict the subsequent incidence of zoster were examined by univariate and multivariate analytic techniques. Intensity of treatment was a key factor in the incidence of zoster. Thirty-six months after initiation of treatment, patients receiving chemotherapy-radiation-chemotherapy had twice the attack rate (27.3%) of those receiving radiation alone (11.5%). The pediatric age group had a significantly higher attack rate (26.6%) than did adults (18.7%). Stage, histology, and laparotomy did not influence the incidence of zoster.
We attempted to treat 5 patients on CAPD with fungal peritonitis without removing the catheter. In 1 case, amphotericin B caused a severe chemical peritonitis. The other 4 patients received amphotericin B intravenously and miconazole or flucytosine intraperitoneally. Recovery was obtained in 3 cases without removing the catheter and in 1 case the patient died.
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The pathological features of 155 adult patients with soft-tissue sarcomas were studied retrospectively, in an attempt to set up a grading system for these tumors. As the first step, seven histological criteria (tumor differentiation, cellularity, importance of nuclear atypia, presence of malignant giant cells, mitosis count, pattern of tumor necrosis and presence of vascular emboli) were evaluated in a monofactorial analysis. Five of these (tumor differentiation, cellularity, mitosis count, tumor necrosis, and vascular emboli) were correlated with the advent of metastases and with survival. A multivariate analysis, using a Cox model, selected a minimal set of three factors (tumor differentiation, mitosis count, and tumor necrosis) the combination of which was necessary and sufficient to retain all the prognostic information. A grading system was elaborated, which turned out to be correlated with the advent of metastasis and with patients' survival. A second multivariate analysis introducing clinical prognostic features showed that the histological grade was the most important prognostic factor for soft-tissue sarcomas. Thus, this grading system appears to be highly interesting because of its prognostic value and the facility of its elaboration. However, its reproducibility should be tested.
The early-phase (20 min) pharmacokinetics of doxorubicin was studied in 18 patients suffering from non-Hodgkin lymphoma and receiving various schedules and/or dosages of the drug. This pharmacokinetics was time-dependent in most patients over a 2-week interval: repeating similar doses in patients leads to a decrease of the drug exposure due to a decrease of the half-life and/or to a decrease of the extrapolation to 0 time (intercept parameter). The pharmacokinetics was generally time-independent within a 6-h interval in most patients. During this time interval, the kinetics was not linear: increasing the dose by large proportions does not lead to a proportional increase of drug exposure. This time- and dose-dependence of doxorubicin pharmacokinetics makes it very difficult to monitor the treatments according to the individual pharmacokinetic patterns of patients.
We used the Cancer Attitude Survey (Haley-Blanchard) to investigate attitudes of general practitioners, oncologists in a cancer center, and medical students (during the second part of medical studies (DCEM), at the beginning and the end of a clinical course, and at the last examination ("Cliniques")) towards cancer and cancer patients. This CAS is designed to determine mainly attitudes on inner resources of patients to cope with cancer, value of early diagnosis, aggressive treatments and preparation for, and acceptance of death. There are significant differences between different groups, and for younger students between the beginning and the end of a clinical course in a cancer hospital. There are also differences between French and American doctors. In comparison with American, French mainly underestimate the inner resources of cancer patients while their attitudes are similar for early diagnosis and aggressive treatment. Such a survey is able to give objective data on present attitudes and also to examine how they change with time.
The authors report 27 cases of inflammatory carcinoma of the breast (T3-T4, M0) and propose: induction chemotherapy (adriamycin, vincristin, methotrexate) conventional local and regional radiotherapy, sometimes complementary surgical exeresis, and a complement of consolidation chemotherapy (cyclophosphamid, methotrexate, fluoro-uracil or adriamycin, vincristin, and methotrexate). In these forms, where the prognosis is very bad, this therapeutic regimen may improve considerably the median remission and survival rates. But important therapeutic progress remains.
The pharmacokinetics of adriamycin was evaluated in the plasma of 12 patients with breast cancer after injection of an i.v. bolus. The patients were suffering from a locally advanced tumor, were free of metastases and had received no prior treatment. They received a chemotherapy consisting in adriamycin (50 mg/m2) on day 1, vincristine (1 mg/m2) on day 2 and methotrexate (6 mg/m2) on days 3, 4 and 5. The response to chemotherapy was assessed as the percentage of reduction of the palpable tumoral mass. Plasma samples were collected at various times after injection of the drug. Adriamycin and its metabolites were extracted using an original column purification technique and were evaluated by high-performance liquid chromatography with fluorometric detection. Pharmacokinetic parameters were calculated with a computer program based upon an algorithm of non-linear function minimization. The three successive half-lives presented little individual variations and were 4.75 min, 0.822 hr and 18.9 hr. On the other hand, the A, B and C parameters were highly scattered. The total plasma clearance of the parent drug ranged from 28.3 to 98.7 1/hr. A highly significant correlation was observed between parameter A and the short-term clinical response. Moreover, a mild correlation exists between the half-life of the 1st phase and the short-term clinical response. We can therefore assume that the efficacy of the drug may be dependent upon its distribution in the organism. Such a relationship may allow the development of new protocols of chemotherapy in order to obtain an optimal distribution of the drug in every patient.
In this retrospective study, we analysed prognostic factors of 334 previously untreated patients with non Hodgkin's malignant lymphoma. The importance of the different prognostic variables was first studied with survival curves. Next, using a "segmentation" method and a logistic regression analysis, we studied the factors influencing the complete remission rate which is the most important prognostic factor. For the "low-grade" lymphosarcomas, with the segmentation method, we obtained five patients groups for which the complete remission rates varied between 7 and 95.5 per cent according to clinical staging, age and mediastinal involvement. For the "high-grade" lymphosarcomas, we obtained four patients groups in which the complete remission rates varied between 8.7 and 84.7 per cent according to mediastinal and sub-diaphragmatic involvement and clinical staging. Lastly, the Cox model was used in order to determine the best variable combination capable of predicting the survival of patients with clinical stages I or II. These variables were pathological grading, complete initial remission, clinical staging and BCG immunotherapy. With scores deduced from the Cox model, we were able to determine three prognostic groups for which the survivals at 3 years were very significantly different (7 to 89%).
Eighteen patients with previously untreated advanced colorectal cancer were treated with a sequential methotrexate-5-FU regimen. One of 16 evaluable patients achieved a partial response. The results of this and other clinical and laboratory investigations reported to date suggest that further study of different doses and schedules of sequential methotrexate-5-FU is warranted.
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74 patients who had adenocarcinoma of the breast that was inoperable at the beginning because of local extension but without inflammation and without diagnosable metastases (T3b, T4, N1, 2 or 3, Mo) were submitted to a therapeutic regime which consisted consecutively of: 1) preliminary chemotherapy, 2) radiotherapy and/or extended radical surgery when there was any residual tumour, and 3) follow-up adjuvant chemotherapy. Two types of combinations of cytostatic drugs were used: adriamycin, vincristin and methotrexate (AVM) for 5-day cycles every 3 weeks, and cyclophosphamide, methotrexate and fluoro-uracil (CMF) in 14-day cycles every 4 weeks. Three to 5 cycles of AVM were used initially, then at first either AVM to a total of 550 mg/m2 adriamycin, or a series of CMF carried on for a year. Complete remission was obtained in 70% of the patients (52 out of 74) at the end of the local-regional treatment. The mean time of remission was 33 months and the mean time of overall survival was 43 months. The best results were obtained in younger women (under 65 years of age) with tumours that were less developed (T3b), and who could take all the adjuvant chemotherapy after they had complete remission. There was no relapse in 37 of the 48 patients in this group (77% of the cases). Overall the treatment was tolerated fairly well and there was no major complication at the time of radiotherapy or surgery. These results are comparable to those from other studies of a similar nature and show a real progress as compared with those that used to be obtained when only local and regional treatments were undertaken. A more thorough follow-up is however necessary since we can hope for improvements to increase the efficacy and tolerance of the treatments, but this form of treatment can here and now be considered as an important factor for improving the survival rate of these very high risk patients.
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From 1965 to 1976, 170 patients with Hodgkin's disease, clinical stages I or II, were treated with radical irradiation. A first group of 42 patients was treated with irradiation alone, a second group of 24 patients received one course of chemotherapy followed by irradiation, and a third group of 104 patients was treated with a sandwich regimen including chemotherapy + irradiation + chemotherapy. Although the treatment were not randomized, the comparison of the results shows a striking improvement in the group submitted to the C + R + C regimen: in this group the plateau of disease-free survival was 90 per cent. This result was obtained after treatment for about 3 months without surgical staging or maintenance chemotherapy. However, this treatment may favor some complications,. mainly the development of a second malignancy; these risks may be decreased by reducing the treatment in patients with good prognosis.
Sixty-two patients with advanced measurable gastric cancer were treated with a combination chemotherapy program of 5-fluorouracil, doxorubicin, and mitomycin (FAM). Forty-two percent of patients achieved an objective partial response. The median duration of remission was 9 months and the median survival for responding patients, 12.5 months. The median survival for nonresponding patients was 3.5 months; all patients were dead by 8 months after initiation of therapy. The median survival of all 62 patients treated with FAM was 5.5 months. An analysis of possible prognostic variables including initial performance status, resectability of the primary gastric tumor, and histologic differentiation of the neoplasm failed to account for differences in patient response and survival. The FAM regimen was well tolerated, producing only moderate bone marrow suppression. These results show that patients with metastatic gastric cancer can be effectively palliated with FAM chemotherapy. The efficacy of this regimen should now be tested in patients with less advanced stages of this disease.
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