First International Workshop on Human Gene Transfer.
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Biomedical subjects
Publications and source records attributed to M Boiron.
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The purpose of exchange and development therapies (EDT) is to reduce the behavioural problems which are the expression of psychophysiological dysfunction. The aim of this study was to reveal the most disturbed psychophysiological functions and their evolution during the course of EDT in 42 children divided into three groups; group I--15 children with pure autism (A); group II--16 children with autism associated with neurological disorders (AA); and group III--11 children with pervasive developmental disorders (PDD). Among the 12 functions analysed, groups AA, A and APDD had respectively 8, 6 and 4 functions in which the score was high (> 2.5), indicating serious disorders (maximum 4). All the dysfunctions improved during EDT. However, each group had certain areas which were more susceptible to treatment. Further analysis of behaviour problems led to a more precise definition of the objectives and to the adaptation of the therapeutic methods to obtain greater effectiveness.
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The combination of chemotherapy and radiotherapy in Hodgkin's disease has been associated with iatrogenic effects. Forty adult patients were studied to evaluate the early toxicity following three courses of ABVD (cumulative dose of doxorubicin [Adriamycin] 150 mg/m2, and bleomycin 60 mg) and mediastinal irradiation at 40 Gy. Cardiopulmonary toxicity was assessed from six months to three years after completion of irradiation. Of the 40 patients, all of whom were in complete remission from Hodgkin's disease, 6 experienced dyspnea on exertion. In studies related to Cardiac toxicity, the left ventricular ejection fraction ranged from 50 to 77% (mean 63%); 8 patients had a minor pericardial effusion, 4 had valvular calcification, and 6 had minimal cardiac abnormalities. With regard to pulmonary toxicity, CT scan showed a small pleural effusion with pleural thickening in 19 patients and mediastinal or apical fibrosis in 15 patients. The total pulmonary capacity value was low (less than 80%), in 19 patients, and decreased carbon monoxide diffusion capacity (less than 70%) was found in 10 patients. We conclude that early cardiac toxicity was absent despite the use of Adriamycin and mediastinal irradiation. Pulmonary toxicity was present but minor, and it may decrease with the use of smaller fraction sizes for mantle field irradiation.
Cardiac presentation of non-Hodgkin's lymphoma is rare and usually associated with a short survival. Two cases were documented and followed-up with echocardiography and magnetic resonance imaging (MRI). The tumoral masses were accurately delineated by MRI. A non-delayed diagnosis ensued and, in association with a multiple drug antimitotic therapy, an improved prognosis obtained.
The quantification of gastroduodenal motility uses invasive methods. The aim of our study was to further characterize the contractility of antrum, pylorus and duodenal bulb in two states, using a new, non invasive fluorographic method. Healthy volunteers (mean age = 28) were involved in this study under fasting conditions (n = 20) and after a meal (n = 20). In both conditions, the subjects have swallowed 250 ml of a barium sulfate solution for fluoroscopic gastrographies taken every 2 seconds, during 30 s. Spot films were analysed using a graphic table and locally developed microcomputer program to generate space-time diagrams of antral and duodenal areas and of pylorus diameters. For each subject, the antral CA, duodenal CB contractilities (maximal variation of antral, duodenal areas in p 100) and pylorus contractility CP (closure during the observation time in p 100) were calculated. CA values were high in the two situations, but did not differ (81.1 p 100 vs 82.5 p 100 post-prandial). In contrast, CP was higher under fasting (54.0 p 100) than in post-prandial (15.0 p 100; p less than .001). Two pyloric motor patterns were observed in post-prandial: A--pyloric contractions in relation with the end of antral contraction B--augmented pyloric resistances observed during the end of antral contraction and also associated with duodenal contractions. CB was low in post-prandial (27.0 p 100) compared to fasting CB (50.8 p 100; P less than .001). This method is reproducible and simple to use. It allows quantification of contractility and coordination in the antrum, pylorus and duodenal bulb. It may be useful to assess gastroduodenal motility under pathological conditions.
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Despite combination of chemotherapy and radiotherapy, some patients with refractory or relapsed Hodgkin's disease (HD) have a bad prognosis. We performed high dose chemotherapy (HDCT) (BCV regimen) with autologous bone marrow transplantation (ABMT) in 26 patients with advanced HD. 11 patients were considered refractory after at least two non cross-resistant chemotherapy regimens and radiotherapy in 8 cases. 15 patients had a poor prognosis relapse (in visceral or irradiated site) after complete remission and they received chemotherapy before ABMT. At the time of transplantation 4 patients had progressive disease with B symptoms and did not respond to HDCT; they all died 3 to 12 months post-transplantation from persistent HD. For the remaining 22 patients, 3 months after HDCT 19 patients (73%) were in complete remission, 2 (8%) in partial remission and one patient died from toxicity. After complete remission 4 patients relapsed at 12 to 18 months and 15 patients are in persistent remission 24 to 46 months after transplantation. These results are encouraging in patients with bad prognostic factors but able to respond to chemotherapy.
Gastric peristalsis has not been studied extensively in patients with dyspepsia. The aim of our study was to further characterize gastric peristalsis in such patients using a newly described fluorographic method. Thirty-two patients with dyspepsia and 18 healthy volunteers were included in our study. Four hours after a standard solid-liquid meal, the subject swallowed 250 ml of a baryum sulfate solution and (100 mm x 100 mm) fluoroscopy of the stomach was performed every 2 s during 30 s. Spot films were analyzed using a graphic table and a amateur microcomputer program. For each subject, the instant velocity, vi, and mean velocity, V, of gastric peristalsis were calculated and used to generate a time-space diagram of contractions, a velocity histogram and an index of propagation, Ip. These parameters were compared to normal values (V = 2.2 +/- 0.2 mm/s; Ip = 2.2 +/- 0.4). When compared with normal values, 3 different motility patterns appeared in dyspeptic patients with a high correlation between V and Ip (P less than 0.01): normoperistalsis (n = 8; 1.8 less than V less than 2.6 mm/s); 1.4 less than Ip less than 30); hypoperistalsis (n = 7; V less than 1.8 mm/s; Ip greater than 3.0) and hyperperistalsis (n = 7; V greater than 2.6 mm/s; Ip less than 1.4). In a 4th group (n = 5), a retroperistalsis was effect observed with Ip less than 0. For 5 other patients, Ip or V was abnormal with atypical motor activity detected on the time-space diagram.(ABSTRACT TRUNCATED AT 250 WORDS)
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We report 2 cases of acute non-lymphocytic leukemia with distinct clinical and karyotypic features shared by therapy-related acute non-lymphocytic leukemia occurring after adjuvant chemotherapy including 5-fluorouracil, doxorubicin and mitomycin C. Our observation suggests a causal relationship between exposure to mitomycin C and the occurrence of acute non-lymphocytic leukemia.
The outcome of advanced Hodgkin's disease has improved since the use of MOPP and ABVD. However 50% of these patients will relapse. Conventional salvage therapy can yield a complete response rate of 50%. However, only 5 to 30 percent can expect to be cured. Autologous bone marrow (ABMT) in reported publications can reach 50 to 80% remission rate in refractory patients with a disease free survival of 40 to 80%. Adverse prognostic factors are: tumor burden, number of prior chemotherapies, response to latest therapy and performance status. At the present time, ABMT is discussed in relapse of poor prognosis with initially stage I to IIIA. Twenty-six patients underwent ABMT at Saint-Louis Hospital. Fifteen were sensitive relapses of poor prognosis, 11 initially refractory disease. After ABMT, 19 were in complete remission including 14 relapses. Disease free survival was 80% for relapsing patients, again 50% for refractory patients (P = 0.001). ABMT should be a tool for refractory patients and relapses of poor prognosis.
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Review on general problems raised by the role of some viruses: parvoviruses, herpes viruses, retroviruses, in the physiopathology of human malignant blood diseases.
Aggressive non Hodgkin lymphoma (NHL) occurs frequently in the elderly and because of drug related toxicity treatment remains controversial. Seventy-two patients over 65 years (68-83 y, median 73 y) with intermediate and high grade NHL were retrospectively studied. We found 22 cases of high grade NHL and diffuse large cell the most frequent type encountered (54%). Seven patients had stage I, 8 stage II, 14 stage III, and 43 stage IV disease. Treatment for localized disease was radiotherapy or chlorambucil, and disseminated stage patients were treated by three different chemotherapy regimens, group I: classic dose chemotherapy without Adriamycin (15 pts), group II: same type of regimen with Adriamycin (45 mg/m2) (42 pts), group III: high dose chemotherapy with Adriamycin (75 mg/m2) (8 pts). Overall complete response (CR) rate was 53% without significant differences between treatment groups. Median duration of survival was 38 months and estimated 5 year survival at 40%. Following complete remission, 15 patients (40%) relapsed. Thirty-seven patients have died, 6 from toxic deaths (5 toxic deaths in group II and III), 28 from NHL, and 3 from other diseases. Toxicity was greater among patients treated with Adriamycin. In a multivariate analysis, the attainment of complete remission was the only factor influencing survival. Our data shows that classical dose chemotherapy leads to the same CR rate and survival as more intensive regimens.
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