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Biomedical subjects

E Rapp

Publications and source records attributed to E Rapp.

32 records · Page 2Linked to original sources

Drug delivery analysis of the Canadian multicenter trial in non-small-cell lung cancer.

PURPOSE: The Canadian multicenter trial for advanced non-small-cell lung cancer (NSCLC) reported survival benefit for chemotherapy when best supportive care was compared with vindesine-cisplatin (VP) and the combination of cyclophosphamide, doxorubicin, and cisplatin (CAP). We examined received drug delivery to document dose-intensity (DI) and total dose of drugs given to various groups in this patient population. PATIENTS AND METHODS: Plots of cumulatively received chemotherapy against time were used to evaluate drug delivery by regimen, major prognostic factors, and response status. RESULTS: Individual CAP patients show a narrow range of received DI, with the median similar to protocol. Drug delivery analysis exposed a wide range of received DI for both drugs in the more intensive VP regimen, and the median received DI was below protocol. The median received DI for cisplatin was still higher for VP than CAP, but only during the first 8 weeks of protocol treatment (20 v 10 mg/m2/wk); thereafter, the ongoing received cisplatin DI was the same (10 mg/m2/wk). The median received DI for cisplatin in each regimen was not influenced by stage, performance status, prior weight loss, sex, or response status. VP-treated patients received a higher total dose of cisplatin than CAP patients (median, 255 mg/m2 v 112.5 mg/m2; P < .0001). Median cisplatin total dose was similar for patients with a chemotherapy response or stable disease and threefold greater than for patients with progressive disease for both regimens. Although patients with chemotherapy response and stable disease had similar survival outcomes for both CAP and VP, the VP regimen had a higher proportion of patients without progressive disease (P = .004), which resulted in an overall survival advantage (P = .01). CONCLUSION: The major prognostic factors for advanced NSCLC do not exert their influence on outcome by affecting deliverable chemotherapy DI. Regimen and treatment response determined total dose. Because stable disease patients usually outnumber responding patients in advanced NSCLC trials, controlled studies should be performed that allow assessment of the impact of total received dose on outcome according to response status.

Adenocarcinoma↗

[Necrotizing fasciitis of the foot. An unknown surgical emergency. Apropos of a case].

INTRODUCTION: The purpose of this study was to review the literature concerning Necrotizing Fasciitis (N.F.) and to discuss a typical case where late diagnosis led to severe consequences. MATERIAL AND METHODS: A young male patient with no pertinent medical history, progressively developed a large swelling of his foot and severe pain 3-4 days following a simple contusion. The absence of an entry site lead to local incision without microbiological study. The patient developed blistering on the leg, then septic shock necessitating amputation. DISCUSSION: N.F. is an infectious necrosis of the sub-cutaneous tissue appearing frequently in surgical or post traumatic contexts. Streptococcal origin is classical but multibacterial anaerobic infection is more and more frequently observed. An entry site is not always found while the affected site becomes red, hot and painful. Evolution is extremely rapid with the appearance of blisters and cutaneous necrotic sites and a severe alteration in the general condition of the patient. The extent of sub-cutaneous necrosis is larger than the affected area of skin. N.F. is a surgical emergency. Treatment consists of complete debridement, sometimes very extensive and mutilating. High dose intra-venous antibiotic therapy is necessary while the benefits of hyperbaric therapy are discussed. Because of the lack of specific clinical signs, diagnosis is difficult and is often made too late. The rapidity of the evolution shows that vital and functional prognosis is better with early diagnosis and treatment even for patients without associated pathology. The rate of mortality is approximately 50 per cent. CONCLUSION: Better information of practitioners allowing a rapid clinical diagnosis could improve the prognosis which is still life-threatening in 1994.

Adult↗

Polychemotherapy in advanced non small cell lung cancer: a meta-analysis.

We did a meta-analysis of all published polychemotherapy vs supportive care clinical trials in patients with non-resectable non small cell lung cancer. 7 studies with more than 700 patients were selected. We used the number of deaths at 3, 6, 9, 12, and 18 months as the endpoints because we were unable to obtain all the individual data. Our analysis showed a reduction in mortality during the first 6 months with polychemotherapy. Although small, this increase in survival, together with an improved quality of life, suggests that polychemotherapy should be recommended for patients with non-resectable non small cell lung cancer.

Antineoplastic Combined Chemotherapy Protocols↗

Dielectric properties of lung tissue as a function of air content.

Dielectric measurements were made on lung samples with different electrode systems in the frequency range 5 kHz-100 kHz. In the case of plate electrodes and spot electrodes, the effects of electrode polarization were partly corrected. An air filling factor F is defined, which is determined from the mass and volume of the sample. The results indicate that the electrical properties of lung tissue are highly dependent on the condition of the tissue. Furthermore they show that the conductivity sigma as well as the relative permittivity epsilon r decreases with increasing F. This is discussed using histological material. Using a simple theoretical model, the decrease of sigma and epsilon r is explained by the thinning of the alveolar walls as well as by the deformation of the epithelial cells and blood vessels through the expansion of the alveoli.

Animals↗

[Histological studies of a tongue-shaped formation at the intertubercular groove in the shoulder joint of the dog].

Radiologically apparent unilateral changes at the intertubercular groove of the humerus were investigated histologically in three dogs and compared with the findings in an unaltered shoulder joint of a dog. Polymethylmethacrylate embedded, undecalcified sections were cut through the sulcus area at the head of humerus and through the biceps tendon, its synovial sheet and the transverse ligament, and were evaluated by light microscopy. While the tendon and soft tissue features were for the most part typical for a normal "gliding" tendon, the respective groove exhibited an again groove-like, 10-12 mm wide and up to 2 mm high exostosis consisting mainly of lamellar bone, filled with hemopoietic and fatty marrow. The normal fibrocartilaginous lining of the groove showed degenerative arthrotic changes in the altered grooves, pointing to mechanical overloading. The possible mechanisms of these ossifications are discussed.

Animals↗

[Light microscopical studies of glaucoma in the cat].

In the paper presented, the histological findings in four cats with glaucoma are reported by means of HE-stained paraffin embedded sections. To each case a clinical anamnesis is given. The authors describe primary glaucomas as well as secondary glaucomas of different aetiology. A dysplastic pectinate ligament can be identified for the first time in a cat. Clinical and histological findings are discussed and compared to the findings in dogs.

Animals↗

Counting the costs of chemotherapy in a National Cancer Institute of Canada randomized trial in nonsmall-cell lung cancer.

An economic evaluation was undertaken of a previously reported National Cancer Institute of Canada (NCIC) trial of chemotherapy in advanced nonsmall-cell lung cancer (NSCLC). That trial had demonstrated a survival benefit associated with the use of either vindesine and cisplatin (VP) or cyclosphosphamide, doxorubicin, and cisplatin (CAP) in relation to best supportive care (BSC). The economic technique used in this evaluation was cost-effectiveness analysis (CEA). All costs were determined from the viewpoint of two provincial health care plans. When compared with BSC, the survival benefit of 8 weeks in favor of patients receiving CAP chemotherapy was associated with an economic saving of $949.49 (in 1984 Canadian dollars). This translated into a savings of $6,171.69 per year of life gained. The mean survival benefit of 12.8 weeks that was obtained with VP chemotherapy compared with BSC was associated with an increased cost of $3,637.60 per patient, or $14,777.75 per year of life gained. The economic evaluation demonstrated that the majority of costs on each of the three treatment arms was related to hospitalization and not to the use of chemotherapy agents. These results compare favorably with estimates of cost-effectiveness (CE) of commonly used treatments for other diseases and demonstrate that a policy of supportive care is associated with costs that may exceed those of active treatment. It is concluded that economic factors should not adversely affect decisions regarding the use of chemotherapy in advanced NSCLC.

Antineoplastic Combined Chemotherapy Protocols↗

Chemotherapy can prolong survival in patients with advanced non-small-cell lung cancer--report of a Canadian multicenter randomized trial.

The survival benefit of combination chemotherapy to patients with advanced non-small-cell carcinoma of the lung (NSCLC) is controversial. To study this question, the National Cancer Institute of Canada (NCIC) Clinical Trials Group conducted a prospective randomized trial comparing best supportive care (BSC) to two chemotherapy regimens, vindesine and cisplatin (VP), and cyclophosphamide, doxorubicin, and cisplatin (CAP). Between February 1983 and January 1986, 23 centers across Canada entered 251 patients on study. Eighteen centers participated in the three-arm schema (150 patients); centers choosing not to participate in a study with a no-chemotherapy arm followed a two-arm schema comparing VP with CAP (101 additional patients). Altogether, 233 patients were eligible. Patients had measurable or evaluable disease, with either distant metastases (82.5%) or bulky limited disease considered inoperable or unsuitable for radical radiotherapy. The treatment groups were comparable in terms of age, sex, performance status, histology, disease extent, and weight loss. The overall response rates (complete response [CR] plus partial response [PR]) on the chemotherapy arms were CAP, 15.3%, and VP, 25.3% (P = .06). Patients on the three-arm portion of the trial had a median survival of 32.6 weeks when treated with VP, 24.7 weeks with CAP, and 17 weeks with BSC. The significance of the differences in survival, adjusted for prognostic factors, is as follows: chemotherapy v BSC, P = .02; VP v BSC, P = .01; and CAP v BSC, P = .05. Toxicity on the chemotherapy arms was significant, with leukopenia of severe or greater degree occurring in 37.8% (CAP) and 40.0% (VP), severe vomiting in 12.2% (CAP) and 23.3% (VP), and severe neurotoxicity in 15.6% (VP).

Antineoplastic Combined Chemotherapy Protocols↗

Synthesis and hypoglycemic activity of benzamidophenyl-alkanoic acid derivates: new inhibitors of gluconeogenesis.

A series of omega-[2-(N-alkylbenzamido)-phenyl]-alkanoic acids was synthesized and tested for its effects on blood glucose concentration in fasted rats and on gluconeogenesis from lactate and pyruvate in isolated perfused rat livers. The compounds led to a dose-dependent and reversible inhibition of gluconeogenesis, with 4-[2-(N-methyl-3-trifluoromethylbenzamido)-phenyl]-butanoic acid leading to a 50% inhibition at 0.02 mM. The compounds lowered blood glucose in fasted rats. No correlation between hypoglycemic effect and inhibition of gluconeogenesis could be detected, however.

Animals↗

Immunocompetent cells in malignant disease in man. II. Clinical and immunologic correlates in a case of non-Hodgkin's lymphoma.

The immunocompetence of the circulating lymphocytes of a patient with non-Hodgkin's lymphoma was evaluated before, during and after treatment. The immunologic features investigated were (a) the degree of blastogenic transformation induced by phytomitogens (phytohemagglutinin-M, concanavalin A and pokeweed mitogen); (b) the formation of E, EA and EAC rosettes; and (c) antibody-dependent, cell-mediated cytotoxicity. Prior to treatment the subnormal in vitro responsiveness of the cells and the very low concentrations of circulating immunoglobulins suggested immunoincompetence. A gradual shift towards normal in vitro values was observed during treatment, which corresponded to the clinical improvement in the patient's condition.

Chemical Fractionation↗

Immunochemotherapy of lung cancer.

After surgical resection of their primary lung cancer, 33 patients were randomized into one of three groups. The first received high-dose methotrexate once per month with citrovorum rescue, for 3 months. The second group were immunized monthly with a homogenate of Freund's complete adjuvant and carefully characterized soluble antigen derived from allogeneic lung cancer cells of appropriate histology, for 3 months. The third group received a combination of methotrexate and immunization monthly, for 3 months. Each patient was monitored immunologically before, during, and after the treatment period, by use of delayed hypersensitivity reactions to recall and cancer antigens, in vitro lymphocyte response to mitogens, and mixed lymphocyte blocking factor activity. The group that received methotrexate showed little change in skin reactivity, a reduction of blocking factor activity, and significant rebound overshoot in in vitro lymphocyte performance. The immunized group showed a tendency to production of blocking factor activity, striking conversion and enhancement of skin reactivity, and little change in in vitro lymphocyte performance. The immunochemotherapy group showed dramatic increases in specific skin reactivity to cancer antigens, up to 2 years after treatment, in vitro lymphocyte rebound overshoot, and reduction of blocking factor activity production. Classic life table analysis of the probability of freedom from metastases in patients with stage-I cancer indicate that the disease-free interval in patients who received methotrexate is longer than in historic and concomitant controls but not as long as in those who received immunization. The best group appear to be those who received combination immunochemotherapy. We emphasize that the small numbers in this pilot study do not yet allow firm conclusions to be made.

Adult↗