[Eprex: historical record and development].
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Biomedical subjects
Publications and source records attributed to D Poisson.
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The pharmacological study of 3-(4-chlorophenylsulfonyl) 4-hydroxy-7-methoxy- coumarine and 3-(4-methylphenylsulfonyl) 4-hydroxy-7-methoxy-coumarine shows that these derivatives present low sedative effects on the central nervous system, particularly due to their actions upon temperature and motility, more accentuated for the chloro-substituted derivative.
Intravenous recombinant human erythropoietin (Eprex Cilag) was used in 28 hemodialyzed children, treated in 3 French paediatric centers, from November 1989 to November 1990. Transfusion dependency disappeared in all cases: the number of transfusions decreased from 7.3 unit/patient/year to 0.6 unit/pt/year. The mean haemoglobin concentration for the whole group increased from 6.6 +/- 0.8 g/dl, to 9.2 +/- 1.2 at 6 months and 9.7 +/- 0.7 g/dl at 1 year. Twenty-two out of 28 children reached the target haemoglobin value of 9.6 g/dl (6 mmol/dL) within a mean time of 16.5 weeks. Poor responses were due to either a premature withdrawal of treatment because of renal transplantation, or too low a dosage for the age. The study showed indeed that the dose requirement was significantly dependent on physical development: the mean dosage required to maintain haemoglobin concentration at the target value was 300 U/kg/week in children weighing less than 20 kg, 222 U/kg/week in 20-30 kg children, and 135 U/kg/week in those weighing more than 30 kg (p = 0.02). The only complication was an increase in blood pressure, observed in 43% of cases. The increase of anti-hypertensive medication was always successful in controlling blood pressure, and hospitalization was required in only one case. The improvement in general condition was obvious, and in several cases, the cognitive abilities seemed to improve. The growth deficit remained unchanged.
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We studied the efficacy of high doses (100,000 IU intravenously (IV)/twice a week) of human recombinant erythropoietin (rHuEpo) in patients with transfusion dependent myelodysplastic syndromes (MDS). Rationale for such dose of IV Epo was the poor in vitro response of MDS erythroid progenitors (CFU-E) to physiological concentrations of Epo, and the usual high endogenous serum Epo levels of MDS patients. Seventeen patients (nine males, eight females) were included, five refractory anaemia (RA), six RA with blasts excess (RAEB), five RA with ringed sideroblasts (RARS). Tolerance was good, except in three patients who experienced severe flu-like syndrome after Epo injection. None of the patients showed hypertension or developed anti rHuEpo antibodies. Three patients (17.6%) with RAEB had 35-60% reduction of transfusion requirements. No progression of disease occurred. Percentage of erythroblasts, endogenous baseline Epo level and in vitro cultures of erythroid progenitors did not correlate with response to Epo treatment. This study shows that very high IV doses induce only seldom and partial improvement in the status of transfusion dependent MDS. This rate of response, not higher than described with lower dosage, probably represents the maximum expectable response to rHuEpo in this category of patients.
The results of annual parasitological coprology in 56 members of the kitchen staff of a hospital over a 6-year period have been studied. Among these subjects, 27 had at least one positive examination. The results were compared with those from other hospitals. Among the parasites found were 2 Strongyloides stercoralis, 4 Schistosoma mansoni and 31 protozoa with direct transmission. The value of this examination is discussed, taking into account the increasing number of immunodepressed patients.
As the importance of recombinant human erythropoietin (r-HuEPO) therapy has been clearly demonstrated in anaemic patients with chronic renal failure (CRF), we carried out an open, non-randomized, non-placebo-controlled trial of high-dose intravenous (i.v.) r-HuEPO (100,000 U twice weekly) therapy in 14 anaemic, transfusion-dependent patients. Clinical response was defined by a rise in haemoglobin concentration to 9-11 g/dl and/or a reduction in the transfusion requirement during the treatment period compared with the 12 weeks before treatment. Eight patients completed the 12-week treatment and 4 were still under treatment, 1 at 10 weeks, 2 at 8 weeks and 1 at 4 weeks. Only those patients completing treatment were included in the efficacy evaluation. After treatment there was no significant change in haemoglobin concentrations, reticulocyte counts, or transfusion requirements. However, the number of patients included is too low to allow any definitive conclusion to be made.
Nosocomial infections by Pseudomonas aeruginosa seen in a general intensive care unit from January 1987 through December 1989 were studied. Use of piperacillin, ticarcillin, cefsulodine, ceftazidime, and imipenem over the same period were recorded. Rate of infection by P. aeruginosa among the 1,844 patients admitted during the study period was 3.2%; 32% of all nosocomial infections during this period were due to P. aeruginosa. The proportion of P. aeruginosa strains exhibiting in vitro susceptibility to ticarcillin rose from 45.5% in 1987 to 59% in 1988 and 86% in 1989. Concomitantly, the proportion of P. aeruginosa strains simultaneously resistant to ticarcillin, piperacillin, cefsulodine and ceftazidime fell from 32% to 18.5% then 0%. A statistically significant correlation was found between the decrease in piperacillin use and the fall in penicillinase-producing ticarcillin-resistant strains of P. aeruginosa. Because piperacillin has undesirable effects on the intestinal flora and promotes the emergence of resistant strains of P. aeruginosa, the authors now use narrow spectrum antimicrobial agents as first line treatment of nocosomial infections.
Twenty men and 23 women aged from 18 to 65 years, who had been under maintenance haemodialysis for 2 to 16 years and whose haematocrit had been below 30 percent for at least 3 months received recombinant human erythropoietin intravenously at the end of each session for one year. Anaemia was corrected in all patients, the delay in response to each dosage variation being about 4 weeks. The necessary maintenance dosage ranged from 96 to 240 u/kg/week. The number of leucocytes increased significantly until the 4th month, from 5880 +/- 1760 to 6600 +/- 1920 per cubic mm (P less than 0.01). During treatment, pre-dialysis blood creatinine concentrations and potassium and phosphate levels rose, while blood calcium levels fell significantly from 2.45 +/- 0.16 to 2.36 +/- 0.19 mmol/l (P less than 0.01). A nonsignificant increase in systolic and diastolic pressures was also observed, from 129 +/- 16 to 134 +/- 18 mmHg (P = 0.06) and from 75 +/- 9 to 78 +/- 10 mmHg (P = 0.07) respectively. Eight patients (18 percent) required antihypertensive drugs or a higher dose of those previously prescribed. There were 7 cases of vascular thrombosis on pre-existing stenosis, and the dosage of heparin during dialysis had to be increased in most patients. This study confirms that erythropoietin plays a major role in the genesis of the anaemia associated with renal failure. The absence of severe complications in this series was probably due to the criteria of inclusion in the study.
We studied the intestinal flora of 23 newborns, whose meconium had yielded a pure culture of Pseudomonas aeruginosa on blood agar medium. Twelve infants had a single serotype of P. aeruginosa in their meconium, 10 had a second serotype and the last infant was carrying three distinct ones. The maximum levels of P. aeruginosa observed during the first week of life were variable among the infants: 1 x 10(3) to 1 x 10(10) CFU/g of stools. The levels diminished progressively afterwards, and after 1 year of age only 1 of the 13 infants examined remained a carrier of P. aeruginosa. In 11 infants a second or a third serotype occurred during the course of the study. The serotypes that appeared secondarily always disappeared before the initial ones. Antibiotics: ampicillin + gentamicin or cefotaxime + netilmicin and colistin which were given to 8 infants had no clear effect on P. aeruginosa levels. Four infants had delayed colonization by Escherichia coli of greater than or equal to 10 days. All 4 had high levels of P. aeruginosa: 1 x 10(7) to 1 x 10(10) CFU/g stool, and antibiotic therapy, rendering it impossible to assess which was the cause of this delay. This colonization by P. aeruginosa did not lead to any clinical trouble.
In a randomized prospective trial, we investigated whether vancomycin (chosen for local microbiological reasons) given by instillation into the oropharynx of intubated neonates could reduce the frequency of pharyngeal and tracheal colonization, and then broncho pulmonary infection. Two groups of 20 neonates intubated for an expected ventilation period of more than 7 days were included in the study. There was no statistical difference between the two groups for weight, gestational age and duration of treatment. One group (V+) received 4 drops of a 5% solution of vancomycin every 8 h. The control group (V-) had no local treatment. Oropharyngeal and tracheal aspirates were collected twice weekly for bacterial examination. During ventilation, colonization occurred in the oropharynx of 5 V+ (on day 18 +/- 10) and 18 V- (on day 5 +/- 2.5; p less than 0.001); the colonization occurred in trachea of 5 V+ (on day 19 +/- 11) and 17 V- (on day 6 +/- 3.6; p less than 0.001). The same bacteria were identified on both sides in all infants colonized. This treatment produced no adverse effects and seemed particularly valid for very low birth weight infants.
Pancreatic enzymes (PE) are prepared as pH-sensitive enteric coated microspheres [Pancrease, Alipase in France (P)], to prevent gastric inactivation of orally administered enzymes. The efficacy and tolerability of P were compared to those of Eurobiol (E) (PE lacking enteric coating) in patients with exocrine pancreatic insufficiency (PI) via an open crossover study conducted at 16 centers in France. Pancreatic insufficiency was diagnosed in patients with signs of chronic pancreatitis who showed steatorrhea (fecal fat excretion greater than 8.0 g/24 h). The dosage of P was 9 capsules/d and that of E, 3 vials/d. Stools were collected for 3 consecutive days at each of the following periods: after 10 d without any PE, and after 21 d of P and E administration. Results were analyzed statistically by the method of Hills and Armitage. Chronic pancreatitis was alcohol-induced in 33 of 35 patients (94%) who entered the study. The group that received P before E (n = 20) was comparable to the group that received E before P (n = 15) in patient and disease characteristics. Eight of 35 patients failed to complete the study for the following reasons: adverse reactions 2 cases, lost to followup 4 cases, dropped out of study 2 cases. The degree of steatorrhea was similar after P and E. However, symptomatic improvement was noted far more frequently with P than with E. Moreover, patients preferred P to E because of drug taste (p less than 10(-4] and ease of drug administration (p less than 10(-3). Drug safety was comparable in the two groups of patients.
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A systematic search for Campylobacter jejuni in stool cultures from children with acute diarrhoea showed within two months that the organism was present in 3 out of 17 children. Apart from diarrhoea, the symptoms were different in each case: one child had febrile dysentery, another exhibited symptoms resembling appendicitis and the third one had chronic diarrhoea with denutrition. The condition regressed spontaneously in two cases and after erythromycin treatment in one. Phase-contrast microscope examination of fresh stools may rapidly point to the diagnosis. Routine search for Campylobacter jejuni should yield information on the incidence and epidemiology of these infections in France.
In a 10-year-old girl admitted to hospital for polyuria and polydipsia, the central nervous system origin of the symptoms was demonstrated by low antidiuretic hormone levels (inferior to 1 pg/ml) and reduction of diuresis after administration of 1-deamino-8D-arginine-vasopressin (DDAVP). A study of the girl's family history showed that the disease was hereditary and autosomal dominant. Intranasal instillations of DDAVP twice daily constitute the best known treatment of the condition.