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Biomedical subjects

C Chastang

Publications and source records attributed to C Chastang.

At least 19 recordsLinked to original sources

A controlled study of recombinant human granulocyte colony-stimulating factor in elderly patients after treatment for acute myelogenous leukemia. AML Cooperative Study Group.

BACKGROUND: Intensive chemotherapy for acute myelogenous leukemia (AML) continues to yield low rates of complete remission and survival among patients over the age of 65 years. Infection-related mortality is particularly high among these patients during the period of neutropenia that follows chemotherapy. We determined the effect of lenograstim (glycosylated recombinant human granulocyte colony-stimulating factor) on mortality at eight weeks (the main end point) and the rate of complete remission among patients with AML who were 65 years old or older. METHODS: After induction chemotherapy with daunorubicin (45 mg per square meter of body-surface area per day for 4 days) and cytarabine arabinoside (200 mg per square meter per day for 7 days), 173 patients with newly diagnosed AML were randomly assigned on day 8 to receive either lenograstim (5 micrograms per kilogram of body weight per day) or placebo, starting on day 9, until there was neutrophil recovery or a treatment failure, or for a maximum of 28 days. Salvage chemotherapy was also followed by lenograstim or placebo. Patients with a complete remission received two consolidation courses of chemotherapy without lenograstim or placebo. RESULTS: The mortality rate at eight weeks was similar in the lenograstim and placebo groups (23 and 27 percent, respectively; P = 0.60), as was the incidence of severe infections. The median duration of neutropenia (absolute neutrophil count < or = 1000 per cubic millimeter) was shorter in the lenograstim group (21 days, as compared with 27 days in the placebo group; P < 0.001). Eight percent of the patients in both groups had regrowth of AML cells. The rate of complete remission was significantly higher in the lenograstim group (70 percent, as compared with 47 percent in the placebo group; P = 0.002). Overall survival, however, was similar in the two groups (P = 0.76). CONCLUSIONS: The administration of lenograstim after chemotherapy for AML did not decrease the mortality rate at eight weeks among patients over the age of 65 years. The patients who received lenograstim had a significantly higher rate of complete remission than those who received placebo. Nevertheless, the overall survival in the two groups did not differ significantly.

Adjuvants, Immunologic

Prosthetic valve endocarditis in the ICU. Prognostic factors of overall survival in a series of 122 cases and consequences for treatment decision.

We carried out univariate and multivariate analysis of outcome among 122 patients with prosthetic valve endocarditis (PVE) admitted to our ICU between 1978 and 1992. The predominant pathogens were Staphylococcus aureus (33%), streptococci (20%), coagulase-negative staphylococci (12%), enterococci (10%), and Gram-negative bacilli (9%). At 4 months, overall survival was 66% (42 deaths). Staphylococcus aureus was the main predictor of death (75% vs 15% with other pathogens). In S aureus PVE, multivariate analysis identified the following predictors of death: prothrombin time < 30% (relative risk [RR]: 8.3), concomitant mediastinitis (RR: 4.9), heart failure (RR: 4.4), and septic shock (RR: 2.6). In PVE due to other pathogens, prothrombin time < 30% (RR: 32.26), renal failure (RR: 7.31), and heart failure (RR: 6.07) were associated with death. In S aureus PVE, survival was higher in patients who received medical-surgical therapy than in those who received medical therapy alone (9/20 [45%] vs 0/20) (p < 0.01). In PVE due to other pathogens, there was no difference in survival between patients who underwent prosthesis replacement (89%) and those who received only medical treatment (81%). Among the 65 patients who underwent heart surgery, the mortality rate and incidence of postoperative paravalvular leakage did not correlate with positive prosthesis cultures. We conclude that non-S aureus and uncomplicated PVE may be managed without valve replacement but that prompt surgical intervention should be required in all other situations.

Adult

Treatment of newly diagnosed acute promyelocytic leukemia (APL) by all transretinoic acid (ATRA) combined with chemotherapy: The European experience. European APL Group.

All transretinoic acid (ATRA) gives complete remission (CR) rates of 80 to 90% in newly diagnosed acute promyelocytic leukemia (APL). However, it has two major drawbacks (1) a rapid rise in WBC in some patients, with potentially fatal ATRA syndrome (2) rapid relapse with maintenance therapy using ATRA alone or low dose chemotherapy. The French APL group therefore designed a treatment approach with ATRA followed by intensive chemotherapy. The latter was administered after CR achievement with ATRA, or was rapidly added to ATRA in case of rapid rise in leukocyte counts. This combined approach, in a pilot study and in a randomized trial, proved superior to intensive chemotherapy alone, by slightly increasing the CR rate but more importantly by reducing the relapse rate. These results were confirmed by the Chinese, Japanese and New York groups. Our group (and other European groups) are now testing in a new randomized trial the better timing of ATRA and chemotherapy administration (ATRA followed by chemotherapy or ATRA plus chemotherapy) and the role (after an intensive consolidation) of maintenance treatment with intermittent ATRA, continuous low dose chemotherapy or both.

Adult

Antibiotic versus maintenance therapy in the prevention of duodenal ulcer recurrence. Results of a multicentric double-blind randomized trial.

OBJECTIVES: Reduction of gastric acid secretion by maintenance therapy and eradication of Helicobacter pylori by antibiotic treatment have been shown to reduce duodenal ulcer relapse. This study compared the effect of two regimens, a 6-month maintenance on an H2 receptor antagonist versus a one-week antibiotic therapy, on the rate of duodenal ulcer relapse in duodenal ulcer patients with gastric H. pylori infection. METHODS: We conducted a 30-week, double-blind, double-dummy, multicentric clinical trial involving 119 patients (97 M, 22 F, mean age 39 +/- 14 years) randomly assigned to a daily dose of 40 mg famotidine for 6 weeks supplemented with, during the first week, either antibiotics (500 mg amoxicillin q.i.d. and 500 mg tinidazole t.i.d.-antibiotic group) or their placebo (maintenance group). Healed patients after 6 weeks entered the 6-month maintenance phase: the maintenance group received 20 mg famotidine at bedtime and the antibiotic group, a placebo. Endoscopy with antral biopsies was performed to allow a rapid urease test, culture and histological examination upon entry, after 6 weeks, 3 months, and 6 months and, whenever symptoms recurred. H. pylori status was regarded as positive if any one of these three tests was positive, and negative if all tests were negative. RESULTS: The 2 treatment groups were well balanced for all baseline characteristics. After 6 weeks, H. pylori was eradicated in 25 (45%) patients in the antibiotic group, and in 1 (2%) in the maintenance group (P < 0.01). In term of intention-to-treat, there was no significant difference in the healing rate after 6 weeks (93 and 83% in the antibiotic and maintenance groups, respectively; P = 0.15) or in the relapse rate after 6 months (13 and 28% in the antibiotic and maintenance groups, respectively; P = 0.17 Log-rank test). However, the overall failure rate (absence of healing, relapse) was lower (P = 0.04, Log-rank test) in the antibiotic group in which all relapses but one were observed in H. pylori positive patients. The rate of ulcer relapse (1/20) in patients of antibiotic group who remained free of H. pylori during the study, was significantly (P < 0.01) lower compared with that of H. pylori positive patients in the maintenance group (11/44). During the first 6-week period, more side effects were observed in the antibiotic group than in the maintenance group (4 vs 1 patient, respectively). CONCLUSIONS: Our results indicate no significant difference between ulcer relapse rates after 6 months following a one-week antibiotic therapy or long-term maintenance therapy. Short-term antibiotic therapy should be considered as a valuable alternative to the long-term maintenance therapy.

Adult

Treatment of newly diagnosed acute promyelocytic leukemia (APL) by a combination of all-trans retinoic acid (ATRA) and chemotherapy. French APL Group.

All-trans retinoic acid (ATRA) is very effective in newly diagnosed acute promyelocytic leukemia (APL), yielding remission (CR) rates of 80 to 90%. However, it is associated with a rapid rise in WBC in some patients, with potentially fatal ATRA syndrome. Furthermore, most patients relapse with maintenance therapy using ATRA alone or low-dose chemotherapy. The French APL group thus designed a treatment approach with ATRA followed by intensive chemotherapy. The latter was administered after CR achievement with ATRA, or was rapidly added to ATRA in the case of rapid rise in leukocyte counts. This combined approach, in a pilot study and in a randomized trial, proved superior to intensive chemotherapy alone, by slightly increasing the CR rate but more importantly by reducing the relapse rate. The French group (and other European groups) are now testing in a new randomized trial the better timing of ATRA and chemotherapy administration (ATRA followed by chemotherapy or ATRA plus chemotherapy), and the role (after an intensive consolidation) of maintenance treatment with intermittent ATRA, continuous low-dose chemotherapy, or both.

Aged

[Estimation by the Hui and Walter method of the sensitivity and specificity of a diagnostic test in the absence of a reference test: results of a simulation study].

Hui and Walter proposed an approach to directly estimate the parameters of diagnostic tests (sensitivity and specificity for dichotomous tests) and the prevalence of the disease in the absence of a reference error-free test, and without imposing any constraint. We performed a simulation study to investigate the finite-sample properties of the proposed estimators for the situation of three tests. We obtained the following results: i) in screening situations (prevalence < or = 0.10), severe bias and poor precision in the parameter estimates occur and this approach should not be used except for studies with a very large sample size (n > or = 2500); ii) in diagnostic situations (prevalence > or = 0.30), the approach is much more reliable and very little or no bias occurs even for small sample sizes (n = 50, 100), except when both the prevalence is very high (p > or = 0.90) and the performances of the tests mediocre (sensitivity and specificity lower than 0.80).

Algorithms

Bone densitometry in patients with multiple myeloma.

PURPOSE, PATIENTS, AND METHODS: We performed dual-energy x-ray absorptiometry in 10 selected patients with aggressive multiple myeloma in whom substantial tumor mass reduction was achieved after high-dose chemoradiotherapy followed by autologous blood stem cell transplantation. RESULTS: In most cases, bone mineral density (BMD) of the spine was initially low (Mean Z score: -2.69, SEM 0.76) and dramatically increased after treatment (mean increase 16.4%; 7.7% with 95% confidence interval 2.2 to 12.2, excluding one patient whose spine BMD increased by 94.8%). In contrast, skeletal roentgenograms, computed tomographic scans, and magnetic resonance imaging did not reveal any significant improvement of patients' bone lesions. CONCLUSIONS: In patients with multiple myeloma, bone densitometry could be a useful way to assess the efficacy of treatment on bone status.

Absorptiometry, Photon

Effects of brief early exposure to partially hydrolyzed and whole cow milk proteins.

Clinical experience ("the dangerous bottle") and experimental evidence indicate that the early life of an infant is particularly important for the development of the immune responses to food antigens. However, the clinical and immunologic consequences of a brief exposure to, or avoidance of, food antigens during the neonatal period in human infants are poorly understood and documented. We present the preliminary results of a prospective controlled study of 256 normal breast-fed infants randomly assigned to receive (blind) either an adapted formula (Nidina) or a partially hydrolyzed formula (Nidal HA) as a supplement to breast-feeding for a few days when necessary, and to be examined at days 5, 90, 150, and 365. The results indicated that (1) the prevalence of clinical symptoms and of total and specific IgE responses was not statistically different in the two groups of infants and (2) infants fed a hydrolyzed formula had median titers of specific IgG lower than those fed an adapted formula; the difference was significant for alpha-lactalbumin at day 90 (p < 0.005) and for alpha-lactalbumin (p < 0.05), casein (p < 0.05), and hydrolyzed formula (p < 0.01) at day 150. Humoral immune responses of breast-fed infants to food antigens thus appear to be modulated by early, short-term exposure to them.

Breast Feeding

Single-dose amoxycillin-clavulanic acid vs. cefotetan for prophylaxis in elective colorectal surgery: a multicentre, prospective, randomized study. The PRODIGE Group.

A prospective, multicentre, randomized trial was carried out in 19 hospitals in order to compare the efficacy of amoxycillin-clavulanic acid with cefotetan as antibiotic prophylaxis in patients undergoing elective colorectal surgery. Since the main purpose of the study was to demonstrate equivalence between the two regimens, the protocol planned the inclusion of 200 patients. Eligible patients were randomly assigned to receive either amoxycillin-clavulanic acid (2.2 g) or cefotetan (2 g) in a single infusion on the induction of anaesthesia. Failure of prophylaxis was defined as occurrence of infection of intestinal origin, either minor (wound cellulitis) or major (abscess, peritonitis, septicaemia) within the 30-day postoperative period. Among 221 randomized patients, 208 (105 amoxycillin-clavulanic acid, 103 cefotetan) aged 66 +/- 12 years (mean +/- SD) were evaluated while 13 were withdrawn. Colorectal cancer was the indication for surgery in 73% of cases. Eleven (10 +/- 6%, 95% confidence interval) and 13 (13 +/- 7%) failures were observed in the amoxycillin-clavulanic acid and cefotetan groups (P = 0.63 chi-square test) respectively. Most infections occurred before the 10th postoperative day (8% failures at this time, estimated by the Kaplan-Meier method). The results of the trial demonstrate that amoxycillin-clavulanic acid and cefotetan have similar efficacy when used for prophylaxis of infection after elective colorectal surgery.

Adult

Outcome of patients with systemic rheumatic disease admitted to medical intensive care units.

The outcome of patients admitted to intensive care units is known to be influenced by such factors as age, previous health status, severity of disease, and diagnosis. To estimate the outcome of such patients with systemic rheumatic diseases and to determine if the severity of these diseases unfavourably influences the prognosis at the time of admission to a medical intensive care unit, the clinical courses of all patients with systemic rheumatic disease admitted to two medical intensive care units between January 1978 and December 1988 were studied retrospectively. Sixty nine patients with systemic lupus erythematosus (n = 16), necrotising vasculitis (n = 19), rheumatoid arthritis (n = 19), and other systemic rheumatic diseases (n = 15) were included. The mean (SD) age on admission into the medical intensive care unit was 53 (17) years and the mean simplified acute physiological score was 12 (5.5). The principal diagnoses on admission were infectious complications (29/69 patients) and acute exacerbation of the systemic rheumatic disease (19/69 patients). The death rate in the medical intensive care unit was 33% (23/69 patients) and was similar to that of a non-selected population with comparable simplified acute physiological score. The death rate in hospital was 42% (29/69 patients). Infection was the main cause of death in the medical intensive care unit (19/23 patients) and the infection was mainly acquired in the unit. Only the simplified acute physiological score on admission was a statistically significant prognostic factor: the simplified acute physiological score in patients who died was 15 (5.2) v 9.9 (4.7) for survivors. Long term outcome analysis showed that 83% (33/40 patients) of patients were still alive after admission to the medical intensive care unit with a follow up time between two months and nine years (mean 38 months). The death rate was relatively high and was mainly due to nosocomial infections. It was not different, however, from that of nonselected patients and the long term prognosis was highly favourable. This shows that the complications are often reversible, particularly infectious applications, and justifies admission to the medical intensive care unit of this group of patients.

Adult

[Seraspenide (acetylSDKP): phase I-II trial study of inhibitor of hematopoiesis protects against toxicity of aracytine and ifosfamide monochemotherapies].

Seraspenide, a synthetic tetrapeptide, inhibits cell cycle entry of normal hematopoietic stem cells. In mice it protects hemopoiesis against the damage caused by cytarabine, cyclophosphamide and carboplatin. Seraspenide has been given to 53 cancer patients undergoing monochemotherapy with cytarabine and ifosfamide in a double-blind cross-over randomized study. A significant protection of peripheral blood cells has been observed. Seraspenide has been devoided of toxicity.

Cytarabine

Six vs twelve cycles for complete responders to chemotherapy in small cell lung cancer: definitive results of a randomized clinical trial. The "Petites Cellules" Group.

Of 320 patients with small cell lung cancer (SCLC) entered into a clinical trial of chemotherapy between January 1983 and September 1985, 106 patients achieved a complete response. The induction chemotherapy used was lomustine 60 mg.m-2 p.o., cyclophosphamide 1 g.m-2 i.v., doxorubicin 45 mg.m-2 i.v. and etoposide 150 mg.m-2 i.v., every four weeks. Lomustine was only given for the first three cycles. Seventy nine of the 106 patients still in complete response after six chemotherapy cycles were subsequently randomized to receive either six more cycles or no more treatment until relapse. In this group of 79 patients, a difference was shown from the time of inclusion between the 51 patients with limited disease and the 28 patients with disseminated disease, with overall median survivals of 395 and 165 days, respectively, (p = 0.0002). No difference was shown between the two treatment groups: the median survival was 332 days from the time of second randomization with a two year survival rate of 28% for the patients randomized to receive six more cycles and 246 days and 22% for those randomized to receive no more treatment (add 147 days to obtain overall median survival). Continuing chemotherapy for more than six cycles to patients in complete response did not improve survival.

Aged

[Peroperative cholangiography in cholelithiasis. Results of a multivariate analysis].

This study was done to select patients with a low risk of common bile duct (CBD) stones in whom operative cholangiography could be avoided. Operative cholangiography was performed upon 511 patients. Two different groups of patients were identified: patients with CBD stones visualized by CBD exploration (n = 90) and patients with no CBD stones at the time of operative cholangiography (n = 42). Multivariate analysis (stepwise logistic regression) showed that five variables were correlated with the presence of CBD stones: size of CBD equal to or greater than 12 millimeters, gallstones equal to or less than 10 millimeters, advanced age, chronic or acute cholecystitis and pas history of biliary colic. Using a scoring system, a group of patients with a low risk (less than 2%) of CBD stones could be easily determined. In this group of patients, operative cholangiography may be avoided.

Adult