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Biomedical subjects

M Henry-Amar

Publications and source records attributed to M Henry-Amar.

At least 109 records · Page 6Linked to original sources

Clinical stages I and II Hodgkin's disease: a specifically tailored therapy according to prognostic factors.

The H5 program in clinical stage (CS) I to II supradiaphragmatic Hodgkin's disease (HD) was tailored to prognostic factors identified in former European Organization for the Research and Treatment of Cancer (EORTC) studies. Among the 494 adult patients included in the study, the 237 patients belonging to the favorable group (H5F) underwent a staging laparotomy (Sx) in order to select the patients who could be treated with limited radiotherapy (RT) only. Thus, 198 patients (84%) with negative laparotomy were treated with RT alone and randomized to either mantle irradiation (M) or extended field mantle plus para-aortic (M + PA) irradiation. Complete remission (CR) was achieved in 99% of the patients. There was no difference in the 6-year relapse-free survival (RFS) rate (74% and 72%, respectively) or survival rate (96% and 89%). Therefore, Sx helped to define those patients who could be treated with M alone in contrast to those who required more aggressive therapy. The 39 patients with positive laparotomy were treated as the unfavorable group (H5U) from onset and randomized to either total/subtotal nodal irradiation (TNI/STNI) or a sandwiched mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) X 3, M irradiation, MOPP X 3 protocol (3M). Although the RFS rate was higher in the 3M arm (100% v 53%; P = .002), the 6-year survival was not significantly different between the two arms (overall, 92%). In the 257 patients with initial unfavorable disease, the Sx was avoided. They were randomized to either TNI/STNI or 3M. In complete responders (96%), the 6-year RFS was 91% in the 3M arm and 77% in the TNI/STNI arm (P = .02). The pattern of failure differed in the two arms: the inverted Y and spleen irradiation controlled occult infradiaphragmatic disease better than MOPP; conversely, less patients begun on MOPP recurred in the involved mantle areas. The difference in 6-year actuarial total survival (TS) (89% and 82%; P = .05 in favor of the 3M arm) was not retrieved after exclusion of the unrelated deaths from the analysis. The two arms produced similar TS in patients under 40 years of age. TNI retains interest, especially in young men wishing to preserve fertility. The overall result shows that when treatment is tailored to initial prognostic factors, excellent results can be obtained in all patient subgroups at minimal morbidity and toxic cost.

Antineoplastic Combined Chemotherapy Protocols↗

Evolution of erythrocyte sedimentation rate as predictor of early relapse in posttherapy early-stage Hodgkin's disease.

A retrospective study was undertaken at the Institut Gustave Roussy (IGR) to determine the predictive ability of changes in the erythrocyte sedimentation rate (ESR) during posttherapy periods for early relapse (within 18 months from start of therapy) and long-term survival in Hodgkin's disease (HD). Three hundred one patients with clinical stages (CS) I or II HD entered in the European Organization for Research and Treatment of Cancer (EORTC) clinical trials were included in this study. All relevant data and long-term follow-up were available for these patients. A stepwise logistic regression was performed to assess the prognostic value of ESR changes independent of other prognostic parameters and treatment. The incidence of early relapse was found to be significantly increased in patients in whom ESR remained elevated (greater than 30 mm at one hour) after completion of therapy, regardless of the value before therapy. This was true whether the ESR was elevated in plateau fashion, oscillating between normal and abnormal, or was lower than at onset, but still abnormal. Moreover, early relapse predicted by elevated ESR posttherapy was associated with poor survival despite subsequent initiation of combination chemotherapy. Thus, the persistence of an abnormal ESR appears to be a reliable indicator for high probability of early relapse and subsequent poor prognosis. This might be introduced as a prognostic variable in the design of future therapy programs for HD.

Adult↗

Late toxicity of radiotherapy in Hodgkin's disease. The role of fraction size.

From 1972 to 1976 patients at the Gustave Roussy Institute were irradiated for Hodgkin's disease using a modified fractionation schedule (3 fractions of 3.3 Gy per week) for operational reasons. From 1964 to 1971 and from 1977 to 1981, a more conventional regimen (4 fractions of 2.5 Gy per week) was used. The rates of the late complications in these two subsets of patients treated with different fractionation schedules at the same total dose of 40 Gy during the same overall time were compared. Mediastinitis was observed in 19% of the '4 X 2.5 Gy/week' group versus 56% in the '3 X 3.3 Gy/week' group. Pericarditis in 0% versus 9%, gastroduodenal ulceration and severe gastritis in 10 versus 21% and small bowel obstruction in 5 versus 8%. When using the linear quadratic model with an alpha/beta of 2.5 Gy to evaluate the equivalent dose of 40 Gy given in 12 fractions of 3.3 Gy when delivered by fractions of 2.5 Gy, a value of 46.6 Gy is found. This difference of 6.6 Gy in the equivalent doses (for late toxicity) is likely to account for the significant increase of late radiation injuries, such as mediastinitis and pericarditis, in the present study. The local relapse rate was found to be slightly lower in the 3 X 3.3 Gy group. However, this possible benefit cannot offset the considerable increase of late complications.

Dose-Response Relationship, Radiation↗

Quantitative risk of second cancer in patients in first complete remission from early stages of Hodgkin's disease.

Thirty-three second cancers, excluding basal cell carcinomas of skin and in situ carcinomas of the cervix uteri, were observed among 1,084 patients in first complete remission from Hodgkin's disease treated from 1964 to 1981 by the Lymphoma Group of the European Organization for Research and Treatment of Cancer and the Groupe Pierre et Marie Curie. Five of these second cancers were acute nonlymphocytic leukemias (ANLL), and five were non-Hodgkin's lymphomas (NHL). The 15-year cumulative proportion was 7.6% for second cancers; 0.7% for ANLL; and 1.2% for NHL. For solid tumors (ST) occurring in a previously irradiated area, it was 1.0% after regional radiotherapy (RT); after extended-field RT, it was 8.2% (P = .009). The relative risk (RR) of ANLL after combined chemotherapy with mechlorethamine, vincristine, procarbazine, and prednisone plus RT (relative to the general population incidence rates) was 39 (P less than .001) during the first 4-year period; it was not significantly increased in patients treated by RT without combined chemotherapy. Similar RR was observed for NHL (RR = 31; P less than .001). Moreover, an increased RR of NHL (RR = 53; P less than .001) was observed in patients treated by RT without combined chemotherapy after 10 years. For ST, no significant increased risk was observed regardless of the treatment. There is, however, a slight tendency for the risk of ST related to extended-field RT to increase after 10 years.

Actuarial Analysis↗

Postoperative pulmonary complications: general anesthesia with postoperative parenteral morphine compared with epidural analgesia.

In a prospective study, patients undergoing abdominal cancer surgery were randomly allocated to receive either general anesthesia with fentanyl intravenously and postoperative analgesia with parenteral morphine (GA group) or general anesthesia combined with epidural bupivacaine and epidural morphine for postoperative pain relief (EP group). Analgesia was tested on a visual pain scale. Pulmonary complications were evaluated by clinical complications, blood gas analysis, x-ray film changes, and pulmonary volumes (vital capacity, forced expiratory volume in 1 second). Measurements were performed on the day before the operation and on the first 5 postoperative days. In the EP group the pain relief was significantly better on the first day (p less than 0.03). Whatever the criteria used, the rates of pulmonary complications were similar in the two groups: clinical complications 21% versus 26%, radiologic complications 50% versus 64% for GA and EP groups, respectively. Postoperative PaO2 and spirometric values were similar in the two groups. Postoperative epidural analgesia may improve the patient's comfort but does not decrease the incidence of pulmonary complications.

Abdomen↗

[Anastomotic fistula after gastrectomy. Diagnostic value of radiologic monitoring. Retrospective study of 123 gastrectomies].

In order to determine the usefulness of systematic radiological exploration after gastrectomy, 123 gastrectomies (39 total, 84 subtotal) performed over a 10-year period were reviewed. Control radiology had been carried out in 51% of the cases. Retrospectively, except for the lower percentage of total gastrectomies the two groups (with and without control radiology) were comparable. The overall incidence of fistula (9%) was similar to that found in the literature, bearing in mind that 90% of gastrectomies in this series were performed for cancer. The only two factors predictive of fistula were the presence of fever or of post-operative focal infection (P less than 0.001). It would appear that control radiology after gastrectomy is indicated only when post-operative fever is present. If this were done the number of useless examinations would be reduced and the cost-effectiveness ratio of radiology would be improved.

Female↗

Pregnancy in IgA nephropathy, reflux nephropathy, and focal glomerular sclerosis.

Fetal outcome was retrospectively studied in 217 pregnancies observed during the past two decades in 93 patients, 34 suffering from IgA nephropathy (IgAGN, 69 pregnancies), 53 from reflux nephropathy (RN, 137 pregnancies), and six from focal glomerular sclerosis (FGS, 10 pregnancies). Overall incidence of live births was 175 in 217 (81%). Fetal loss, corrected for induced abortions, was 10 in 66 (15%) in IgAGN, 18 in 129 (14%) in RN, and 2 in 10 in FGS. Renal failure and hypertension preexisting prior to conception or developing early in pregnancy were the most important factors associated with unsuccessful fetal outcome whereas urinary tract infection had limited effects in RN patients. Influence of pregnancy on the course of maternal renal disease was evaluated in the same groups of patients. An abnormally rapid deterioration of renal function was observed in three of the women with IgAGN and in one of the RN patients (with an additional case among 46 further female RN patients) but in none in the FGS group. All five women experiencing functional deterioration had a serum creatinine (SCr) level of greater than or equal to 200 mumol/L (2.3 mg/dL) and hypertension at conception. Hypertension in pregnancy was highly predictive of recurrence of hypertension in subsequent pregnancy and of the remote development of permanent hypertension in IgAGN patients. We conclude that when renal function is preserved, pregnancy is usually successful and no deleterious effects on maternal renal disease are to be expected in patients with IgAN, RN, and probably FGS.(ABSTRACT TRUNCATED AT 250 WORDS)

Biopsy↗

Comparative translocation of enteropathogenic Campylobacter spp. and Escherichia coli from the intestinal tract of gnotobiotic mice.

In C3H gnotobiotic mice, no significant difference was observed between the translocation of nine clinical isolates of enteropathogenic Campylobacter spp. and that of seven nonisogeneic Escherichia coli strains with or without various determinants of pathogenicity. In addition, there was no correlation found between the intensity of translocation of Campylobacter strains and the signs of invasiveness in the patients from whom the strains had been isolated.

Animals↗

Rationale for ACE inhibition in the elderly: treatment of arterial hypertension with enalapril.

A randomized, double-blind, placebo-controlled trial was conducted with 32 elderly patients (aged 75-97 years) with uncomplicated essential hypertension, to evaluate the efficacy and tolerance of enalapril, an angiotensin-converting enzyme inhibitor. It was given over an 8-week period in doses from 20 to 40 mg/day and was compared with an identical placebo. Enalapril caused a significant reduction in systolic blood pressure (SBP) and diastolic blood pressure (DBP) by the 2nd week, an effect that persisted through to the 8th week (190 +/- 16/102 +/- 7 to 151 +/- 19/85 +/- 11 mm Hg); 67% of patients had their pressures normalized (less than 160/95 mm Hg). BP was also significantly decreased by the 8th week under placebo (183 +/- 16/101 +/- 9 to 165 +/-21/91 +/- 13 mm Hg), but only 35% of patients attained a normal pressure. Heart rate did not change with treatment. Enalapril caused an increase in plasma renin activity (1.22 +/- 0.08 to 3.66 +/- 2.50 ng/ml/h), whereas aldosterone levels remained unchanged. There was a mild, significant elevation of creatinine level with enalapril but other laboratory parameters, including serum potassium, were unaltered. Two deaths occurred in the enalapril group, but were not considered to be treatment-related. The drug was otherwise well tolerated. Serum enalapril concentration was assessed in 10 patients taking 20 mg/day over an 8-day period. At equilibrium, the level was 22.3 +/- 5.0 ng/l and it correlated both with converting enzyme inhibition and with renal function. Enalapril is shown to be an effective and well-tolerated antihypertensive medication in elderly patients.

Age Factors↗

[Comparative effectiveness of ranitidine (150 mg X 2) and cimetidine (400 mg x 2) in the treatment of acute duodenal ulcer. A French multicenter controlled clinical trial].

In a single-blind multicenter trial, 444 patients with duodenal ulcer (DU) proven by endoscopy were randomly assigned to treatment with either ranitidine, 150 mg, or cimetidine, 400 mg, morning and evening. Clinical assessments were carried out at 2 and 4 weeks and endoscopy at 4 weeks. The patients in the 2 groups were comparable. Cumulative healing rates at 4 weeks were 78.3 p. 100 in the ranitidine group (n = 226) and 65.6 p. 100 in the cimetidine group (n = 218) (p less than 0.003). Pain at the start was of similar severity in both groups, and disappeared at the same rate under ranitidine or cimetidine: 64 p. 100 patients were painless at 1 week, 80 p. 100 at 2 weeks and 88 p. 100 at 4 weeks. Thirty-eight patients complained of mild side effects: 22 on ranitidine (2 trial withdrawals) and 16 on cimetidine (1 trial withdrawal). Multifactorial analysis (logistic model) revealed that linear ulcers had a lower healing probability than round ulcers (p less than 0.002) whatever the treatment group (cimetidine: 47 p. 100 vs 68 p. 100, ranitidine 57 p. 100 vs 80 p. 100 respectively). Smoking habits (p less than 0.057) and age less than 40 years (p = 0.056) did not significantly influence healing rates, although smokers and younger patients under cimetidine had the lowest healing rate. Thus, at the dosage used in our trial, ranitidine is more efficient for healing DU at 4 weeks than cimetidine but not for pain relief.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

[Arterial hypertension in the elderly. Double-blind study versus placebo of the efficacy and tolerability of an alpha-beta blocker: labetalol].

The purpose of this study was to investigate the efficacy and safety of labetalol, an alpha and beta-adrenergic receptor blocking agent in 32 patients aged from 72 to 97 years (mean = 85 years) with blood pressure (B.P.) greater than or equal to 160/95 mmHg. This study was carried out in a double-blind, randomized, placebo-controlled design. After 6 weeks of treatment with labetalol (mean dose = 235 +/- 47.5 mg/day), the systolic pressure was lowered from 187 +/- 24 to 145 +/- 28 mmHg (p less than 0.001) and the diastolic pressure from 98 +/- 10 to 82 +/- 9 mmHg (p less than 0.001). Likewise, in the placebo group, both systolic and diastolic pressures were significantly reduced but the changes were significantly greater in the labetalol group, -33 +/- 26 versus -13 +/- 20 mmHg and -14 +/- 10 versus -8 +/- 14 mmHg respectively. Labetalol achieved B.P. control (160/95 mmHg) in 64% of the treated patients, compared to 40% in the placebo group. Two patients on labetalol discontinued their treatment due to side-effects (one bradycardia and one cutaneous reaction) compared with one patient on placebo (cardiac failure). Two other cases in the labetalol group had side-effects (one fatigue and one dizziness) which prevented increasing the treatment as necessary.

Aged↗

Aberrant breakpoints in chronic myelogenous leukaemia; oncogenes and fragile sites.

Three hundred and twenty-five aberrant breakpoints in chronic myelogenous leukaemia (CML) with Philadelphia chromosome variant were reviewed. Eight chromosomal bands (3p21, 6p21, 7p22, 11q13, 12p13, 17p13, 17q21, and 17q25) were found to be highly involved. Apart from 17q25, all these bands correspond to oncogenes sites and/or sites involved as primary breakpoints in cancer.

Chromosome Banding↗

Histopathological predictive factors in Ewing's sarcoma of bone and clinicopathological correlations. A retrospective study of 261 cases.

A retrospective multifactorial analysis on 261 previously untreated patients with Ewing's sarcoma (Es) of bone has been carried out in order to ascertain the prognostic value of several histological variables on survival. Among those cases accepted as Es, 208 (80% of the patients) were considered to be "typical Es", while 40 (15%) displayed a large cell predominance, being subclassified as "atypical large cell Es". Furthermore, 13 patients (5%) possessed tumours of endothelial-like appearance. Eleven cases which displayed a mixed histological configuration were finally included within one of the three previous groups according to their predominant histological pattern. After adjustment for therapeutic regimens and initial location of the tumour, only two histological characteristics remain significant; i.e. the presence of necrosis (p = 0.002) and, to a lesser degree, the presence of filagree "en damier" pattern (p = 0.08), both of which are of poor prognostic value. From this study, it can be assumed that the morphological (and possibly histogenetical) heterogeneity of Es of bone has no prognostic influence on survival.

Bone Neoplasms↗

The contribution of clinical trials to the treatment of patients with early stages of Hodgkin's disease.

An analysis of the results that have been obtained in several recent controlled clinical trials showed that the inclusion of combination chemotherapy in the initial treatment of Hodgkin's disease significantly improved relapse-free survival but did not improve survival. This is due to the high efficacy of salvage chemotherapy. Paradoxically, the advent of powerful combination chemotherapy makes initial treatment by radiotherapy alone possible in a large proportion of patients with early stages of Hodgkin's disease. Prognostic factors have been identified by a multivariate analysis of the results obtained in the three controlled clinical trials carried out by the EORTC. These factors can help to delineate the subsets of patients who can be treated initially by radiotherapy alone with an acceptable relapse rate and to adjust the size of the radiation fields. The two prominent prognostic factors are: a combination of systemic symptoms and erythrocyte sedimentation rate the number of lymphatic areas involved.

Adult↗

[Data collection from patients treated for Hodgkin's disease. Relation to quality of life].

One hundred and fifty patients treated for Hodgkin's disease (stage I to IIIA) in a cooperative trial, answered a questionnaire dealing partly with their information, after 2 to 7 years of complete remission. This information appears insufficient for the majority of patients (52%), at least as far as treatment and its complications are concerned. There are many significant relations with other parameters which suggest that a good level of information may improve quality of life of patients. These observations tend to increase information of patients with Hodgkin's disease, provided it is adapted to each patient.

Follow-Up Studies↗

[Psychosocial repercussions of the the treatment of Hodgkin's disease. Assessment by questionnaire with 150 patients].

One hundred and fifty patients, treated for Hodgkin's disease (stages I-IIIA) in a cooperative trial and remaining in complete remission after 2 to 7 years, answered a questionnaire dealing with psychosocial status and quality of life. Many informations were gathered and studied by multiparametric methods. Quality of life of patients appears determined by three kinds of parameters: patients' characteristics (age, sex, family and work status); stage of the disease determining the intensity and duration of treatment; practical conditions of treatment. These last parameters may be improved by therapeutic team and all care-takers to decrease bad consequences of disease and treatment and also to increase quality of life after cure.

Adolescent↗