Experience of the Institut Gustave-Roussy in alternating radiotherapy and chemotherapy schedules as induction treatment in limited small-cell lung cancer.
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Biomedical subjects
Publications and source records attributed to F Thomas.
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Progress achieved in the understanding of small cell lung cancer (SCLC) include: the establishment and characterization of cell lines with the identification of a variant type with poor prognosis; the use of non-specific biochemical markers such as neuron specific enolase (NSE) and calcitonin; the generation of monoclonal antibodies (MoAbs) directed against SCLC antigens; growth factors including GRP and IGF. GRP or human bombesin produced by the tumor cells favours their own growths; in cytogenetics, with the observation of a characteristic chromosomal abnormality: the deletion of the short arm of chromosome 3 (3p 14-23). The region deleted is currently under study to identify the genes potentially involved in the oncogenesis of SCLC. the activation of several oncogenes: C-myc, N-myc, L-myc, Myb, Raf-1. The amplification of C-myc favors the tumor cell progression and is related to a bad prognosis. This biological approach has confirmed the neuroendocrine origin of these tumor cells (as a result of protein studies of the cytoskeleton and of MoAbs); it has allowed the use of tumor markers in the diagnosis and work-up of SCLC and the consideration of new therapeutic approaches. Current studies concern the deletion of 3p- and the integration of the cytogenetic data, growth factors and oncogenes in a coherent model of the genesis of SCLC.
This study reviews the outcome of 17 hypothermic patients air evacuated by a civilian helicopter transport service. Age (33 +/- 23), type and duration of exposure, and rewarm methods were examined for each patient. Temperature (T), heart rate (HR), blood pressure (BP), respiratory rate (RR), Glasgow coma score (GCS), trauma score (TS), CRAMS score (CS), and cardiac rhythm in the pre-hospital setting and in the emergency department (ED) were compared to outcome. Eight of the patients had extensive exposure to a cold environment ranging from 4 h to 10 d. The remaining 9 patients were exposed to cold water ranging from 15 min to 4.5 h. By severity of hypothermia as measured in the ED, 6 patients who were hypothermic at the scene were normothermic (t greater than 35 degrees C), 5 patients were classified as mild (t = 35-31.5 degrees C), 3 as moderate (T less than 31.5-25.5 degrees C), and 3 patients were severely hypothermic (T less than 25.5 degrees C). The GCS, TS, and CS were not indicative of outcome. During rewarming, 3 patients had paradoxical temperature drops, and 5 patients had atrial fibrillation. Three patients required cardiopulmonary resuscitation in the field. Two were discharged with resolving disabilities, and 1 expired. No ventricular fibrillation or J waves occurred. All patients were effectively rewarmed without incident. All patient disabilities and the single fatality were not directly related to hypothermia. There were no long-term adverse consequences of helicopter transport in these hypothermic patients.
We conducted a randomized prospective study to compare the efficacy of oral miconazole and ketoconazole in the treatment of candida esophagitis in acquired immune deficiency syndrome (AIDS) patients in Haiti. Twelve AIDS patients with endoscopic and microscopic diagnoses of candida esophagitis were placed on either oral miconazole or ketoconazole for 10 days. All six patients receiving oral miconazole, and four of the six receiving ketoconazole had complete resolution of their esophageal lesions at the end of treatment. We conclude oral miconazole is at least as effective as ketoconazole in the treatment of candida esophagitis in AIDS patients.
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The Vietnam War heightened civilian awareness as to the use of helicopters for medical evacuations. This led to the initiation of federally funded projects aimed at determining whether helicopters were practical for civilian aeromedical transports. In 1972, a Department of Transportation (DOT) summary concluded that helicopters for civilian medical transports were largely economically prohibitive and provided limited medical benefits in limited locales. Despite this report, in 1972 St. Anthony Hospital initiated a hospital-based emergency medical helicopter service (HEMS). This paper provides a historical review of the individuals and events responsible for the early success of the nation's longest operating civilian hospital-sponsored helicopter service. The author concludes that the early success of this program was due in part to the selection of an affordable, high altitude, helicopter; rapid response times to the scene of injury; the development of excellent EMS communications systems; the use of specialty trained flight crewmembers; and integration of HEMS into the existing EMS system.
The spleens removed in 76 consecutive staging laparotomies for Hodgkin's disease were studied. The spleens were divided from superior to inferior pole into anterior and posterior halves and each half further divided into superior, mid, and inferior sectors. Sectors were studied grossly and microscopically and involvement by Hodgkin's recorded. Of the 23 positive spleens, all sectors were positive in 12, 5 sectors positive in 1, 4 sectors in 3, 3 sectors in 3, 2 sectors in 1, and 1 sector in 2. In one spleen, four sectors were involved but were not marked properly to allow identification of which four, and one spleen with fairly diffuse disease was not handled according to protocol, remaining an "indeterminate" positive. From the anatomic distribution, a lower pole hemisplenectomy would have removed disease in 22 of 23 spleens and likely would have shown disease in the diffusely involved "indeterminate" spleen. An upper pole hemisplenectomy would have missed disease in one spleen and possibly in the "indeterminate" spleen. Either approach would have missed disease in around 1% of the 76 cases. The addition of a biopsy of the opposite pole that remains is technically feasible and would reduce this small incidence of undetected abdominal disease. With the increasing appreciation of the importance of the immunologic functions of the spleen, alternative techniques for determining splenic involvement have been proposed. From this study, hemisplenectomy appears to be an attractive alternate that preserves the vital functions of the spleen with a minute risk of overlooking the presence of Hodgkin's disease.
Nasopharyngeal carcinoma (NPC) is a human epithelial cancer that is constantly associated with the Epstein-Barr virus (EBV). Investigations on this tumor have been limited so far by the difficulty of culturing NPC cells for long periods. C15 is an NPC tumor that has been successfully carried in nude mice for greater than 2 yr. C15 cells isolated from the animal were shown to produce a soluble factor with interleukin 1 (IL-1) activity. Its biochemical (Mr, approximately equal to 17,000; pI approximately equal to 5) and immunological properties are identical to those of IL-1 alpha. RNA gel blot analysis showed IL-1 alpha, but not IL-1 beta, transcripts in C15 cells, in sharp contrast to monocytes that express IL-1 beta predominantly. Media from short-term cultures of fresh NPC biopsies also contained a strong IL-1 activity. Several lymphoblastoid cell lines obtained by EBV infection of normal B lymphocytes have been shown to produce IL-1 and use it as an autocrine growth factor. The production of IL-1 by malignant EBV-containing epithelial cells indicates that different types of EBV-infected cells produce IL-1. A relationship might exist between EBV and constitutive production of IL-1. The IL-1 produced by the malignant epithelial cells in vivo could stimulate the development of the pronounced T-cell infiltrate observed in NPC tumors.
This report extends previous studies demonstrating that prolonged acceptance of incompatible kidney allografts in rhesus monkeys can be achieved by a short recipient rabbit antithymocyte globulin (RATG) treatment course followed by donor bone marrow infusion on day 12 without a requirement for chronic immunosuppression. Serial studies of antilymphocyte cyctotoxic antibody in recipients' sera following RATG injections showed pan-lymphocyte-reactive antibody present until day 10 posttransplant. On days 11 and 12, pan-lymphocyte-reactive antibody was no longer detectable, but cytotoxic antibody specific for mature T cells remained in recipients' sera. These findings might explain the critical time relationship between antithymocyte globulin treatment and donor bone marrow infusion, and further suggest that the tolerance-promoting cell in donor bone marrow is not a mature T cell, but rather a pre-T or a non-T cell. Finally, it was found that this treatment protocol resulted in development of lymphoid nodules in the transplanted kidney that express a CD8-positive, FcIgG-receptor-positive phenotype and appear to be of donor origin. The possibility of a veto cell type of mechanism is discussed as an explanation for the promotion of allograft acceptance in this model.
To evaluate the financial effects of diagnosis-related groups, we compared 128 Medicare and 183 non-Medicare cardiac patients aeromedically evacuated to a major referral center for critical care. A significant difference (p less than 0.05) was found between Medicare patients vs non-Medicare patients for age (71 +/- 7 vs 51 +/- 9 years) and mortality (13 percent vs 6 percent). No significant difference was found for admissions to the intensive care unit (95 percent vs 95 percent), mean length of stay in intensive care (4.7 +/- 5.3 vs 3.9 +/- 5.4 days), mean length of hospitalization (9.6 +/- 7.5 vs 7.9 +/- 7.0 days), mean number of International Classification Diagnoses (ICD-9) surgical operations (0.8 +/- 1.3 vs 0.6 +/- 1.2), and mean number of ICD procedures (3.0 +/- 2.3 vs 3.3 +/- 2.1). The average cost of care ($13,427 +/- $12,700 per patient) for Medicare patients was higher but not statistically different from non-Medicare patients ($10,474 +/- $10,114 per patient). Prior cost-based Medicare payments ($10,594 +/- $9,861 per patient) have been significantly (p less than 0.01) reduced by 24 percent under the Medicare diagnosis-related group (DRG) prospective payment system ($8,024 +/- $4,824). The DRG payments are significantly less than (p less than 0.001) and provide only 60 percent of the true hospital cost required to care for Medicare cardiac patients referred for tertiary care ($13,427 +/- $12,700 per patient). A Medicare DRG system adopted by third-party payers would reduce present hospital revenues from $9,524 +/- $8,422 per patient to $7,968 +/- $4,800 per patient and would provide only 68 percent of the cost required in the care of all cardiac patients referred for tertiary care ($11,690 +/- $11,344). The results of this study indicate that hospitals that receive large numbers of seriously ill cardiac patients, especially Medicare patients, referred for critical care are at a significant financial disadvantage under the Medicare DRG system. Future economic pressures may prohibit critical care treatment centers from accepting large numbers of cardiac patients referred for intensive care and reimbursed under the current Medicare DRG payment policy.
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The role of radiotherapy in small cell carcinoma of the lung is unsettled; however, the radiosensitivity of this neoplasm is unquestioned. The ability of radiotherapy to cure or improve patients with this disease is still undergoing study. A review of this challenging subject is presented.
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