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Biomedical subjects

P Carpentier

Publications and source records attributed to P Carpentier.

At least 19 recordsLinked to original sources
PubMed1992

A European Organization for Research and Treatment of Cancer--Genitourinary Group phase 2 study of chemotherapy in stage T3-4N0-XM0 transitional cell cancer of the bladder: evaluation of clinical response.

From 1986 to 1990 the European Organization for Research and Treatment of Cancer--Genitourinary Group conducted a phase 2 trial of neoadjuvant chemotherapy in patients with stage T3-4N0-XM0 transitional cell carcinoma of the bladder. The objectives were to evaluate the clinical response in relation to the pathological response, and to measure the side effects of chemotherapy. Of 171 patients entered 136 were fully evaluable: 18% had clinical complete remissions, 36% had clinical partial remissions, 39% had no clinical remissions and 10% had unknown response. A selected subgroup of 76 patients underwent cystectomy after 2 or 4 courses of chemotherapy: 2 were not evaluable for pathological response because of preoperative radiotherapy after neoadjuvant chemotherapy, 16 had a pathological complete remission, 7 had a pathological partial remission and 51 had no pathological remission. Comparison of the clinical response or T category only after 2 courses of chemotherapy with the pathological response after 2 or 4 courses of chemotherapy showed that in a number of patients the disease status could be downstaged to pathological complete or partial remission by additional courses of chemotherapy. If the discrepancies between clinical and pathological responses, or between T and P categories, induced by further downstaging after additional chemotherapy were left out, it was shown that clinical complete and partial remissions were a heterogeneous group but nonresponders could be delineated with a 100% accuracy by clinical response evaluation and transurethral resection biopsy only. Furthermore it seems important to establish the number of chemotherapy courses to induce a maximal response of the primary tumor.

Adult↗
PubMed1992

Effects of paraldehyde on the convulsions induced by administration of soman in rats.

The ability of paraldehyde, a potent central nervous system depressant, to prevent the convulsions induced by the organophosphate soman, an irreversible inhibitor of acetylcholinesterase, was studied in rats. Paraldehyde (0.1-500 mg/kg, im) administered 10 min before soman (100 micrograms/kg, sc) did not protect against seizures. Co-administered with atropine sulfate (10 mg/kg, im), paraldehyde produced a clear dose-dependent anticonvulsant response. Although this pre-treatment could delay the occurrence of death, it did not produce any change in the soman-induced 24 h mortality rate. Thus, co-administration of paraldehyde and atropine sulfate might constitute a valuable tool to be used against the convulsant consequences of soman poisoning. However, supplementary pre-medication, in addition to paraldehyde and atropine sulfate, remains necessary to improve the antilethal capacity of the pre-treatment.

Animals↗
PubMed1992

Pharmacokinetics of temafloxacin in humans after multiple oral doses.

The multiple-dose pharmacokinetics and tolerance of temafloxacin, a new fluoroquinolone antibacterial agent, were evaluated in healthy volunteers. Temafloxacin was found to be well tolerated when administered orally every 12 h for 7 days at doses of 100, 200, 300, 400, 600, and 800 mg. Steady-state maximum and minimum concentrations in plasma were proportional to dose, averaging slightly over 1.0 and 0.5 microgram/ml/100 mg administered. Analyses of variance found no significant differences among the dosage groups in total apparent clearances (CLT/F), renal clearances (CLR), or nonrenal clearances, which averaged 197, 119, and 78 ml/min, respectively. The half-life increased slightly with dose, averaging 8.4 h overall. The extent of absorption of temafloxacin was quite reproducible, with day-to-day intrasubject variability in minima averaging under 10%. Renal glomerular filtration of unbound drug was the dominant elimination process; however, tubular secretion and reabsorption also appear to occur. Secretion was estimated to account for about 12% of CLT/F during a regimen of 600 mg every 12 h. CLR was relatively constant for urine flow rates above 1 ml/min, but reabsorption appeared to occur under low-flow conditions, resulting in day-versus-night differences in CLR. Intersubject variability in CLT/F over the eightfold range in dosage was only 20%, and 60% of this variance was accounted for by differences in body surface area (or lean body mass), concentration in plasma, and urine flow rate. Overall, it appears that the pharmacokinetics of temafloxacin are essentially linear, reproducible within a subject, and predictable among subjects.

Administration, Oral↗
PubMed1992

Soman-induced phosphoinositide hydrolysis in rat hippocampal slices: biochemical characterization.

The effects of the organophosphate acetylcholinesterase (AChE) inhibitor soman were investigated on different receptors coupled to phosphoinositide (PPI) breakdown on hippocampal slices in vitro. We observed that muscarinic receptor subtypes M1 and M3 are involved in the increase of intracellular inositol phosphate, which is consistent with the procholinergic effect of soman induced by inhibition of AChE. Although the M2 receptor subtypes are known to be coupled to the cAMP second messenger, we demonstrated that in vitro, under soman, they are also involved in the PPI turnover. The other receptor subtypes known to be linked to PPI hydrolysis are not involved in this model of stimulation.

Animals↗
PubMed1992

[Use of an active clinical maneuver for diagnosis of popliteal artery entrapment].

Overall incidence rate of popliteal artery entrapment syndrome is certainly underestimated. The aim of this work was to test and to evaluate the interest of a clinical maneuver of active and repetitive ankle extensions in upright position, for the screening, the diagnosis and the follow-up of patients with popliteal artery entrapment. During a 3 year period, this maneuver was used in 10 patients (16 popliteal artery entrapments) and in 50 age-matched controls. The results of the maneuver were compared to the results of functional vascular investigations. For all the patients the maneuver had to be stopped before 20 movements whereas it could be continued up to 50 movements for all the controls. The maneuver was easy to perform, reliable and constant in its results. The earlier the maneuver was stopped the more critical was the trouble at functional vascular investigations. We believe that this maneuver is of great help for early diagnosis of popliteal artery entrapment, assessment of its severity and follow-up treated patients. It could also help to detect athletes with asymptomatic popliteal entrapment.

Adolescent↗
PubMed1992

Extracellular acetylcholine changes in rat limbic structures during soman-induced seizures.

Extracellular acetylcholine (ACh) levels were determined, by intracranial microdialysis, in medial septum, amygdala and hippocampus (CA1, CA3, dentate gyrus) of rats during seizures induced by systemic administration of soman (pinacolyl methylphosphonofluoridate), a potent inhibitor of acetylcholinesterase (AChE). In all septo-hippocampal areas a two phase variation was observed: a primary increase in ACh during the pre-seizures period, followed by a decline after 10 to 20 min of seizures and then a second release at 50 min of seizures. In amygdala a progressive increase of the ACh level reached a maximal value at 50 min. ACh levels than returned to basal values in all areas. Hippocampal AChE activity remained totally inhibited throughout the experiment. Possible dynamic phenomena underlying these variations (blood-brain barrier opening, autoregulation of release) are suggested. The present results are compared to previous reports about glutamate changes in the same areas during soman seizures. This comparison gives evidence that in septo-hippocampal areas the glutamatergic system is recruited after an early accumulation of extracellular ACh. The respective roles of ACh and glutamate in triggering and maintenance of soman seizures activity are discussed.

Acetylcholine↗
PubMed1992

[Prospective etiologic study of 128 patients with ambulatory dep vein thrombosis].

Etiology of deep vein thrombosis in ambulant patients (DVTA = TVPA in text) varies: cancer, blood disease, infectious focus, dysimmunity syndrome, dysglobulinemia, extrinsic compression, metabolic disorder, anomaly of hemostasis. A prospective study was carried out between June 1988 and September 1989 by angiologists in 5 regions of France to evaluate the diagnostic rentability of an epidemiologic survey and to determine possible distinctive characters of DVTA. The survey was comprised of a questionnaire, a full clinical examination and screening tests: chest x-ray, abdominopelvic ultrasound imaging, a-uro/gynecologic examination, full blood count, serum iron, ferritin, uric acid, triglycerides, cholesterol, protein electrophoresis, antinuclear antibodies, circulating anticoagulant, hemostasis factors and liver function tests. The study included 128 patients, mean age 60 +/- 16 years with a DVTA developing without a previous immobilization. The usual predominance in the left leg was not observed. The etiology was identified in 33 cases, including 20 (15.6%) as a result of the screening tests: anomalies of hemostasis (8), blood diseases (3), dysimmunity syndromes (4), extrinsic compression (3), cancer metastasis (1) and hypertriglyceridemia in a diabetic (1). The screening procedure was of no greater value in the absence of a triggering or predisposing factor, on the contrary. An anomaly of hemostasis was detected more frequently in the presence of local or regional triggering factors in the men (4 out of 4) and in the women on the pill (4 out of 4). The number of cancers discovered following screening (2%) was smaller than that expected according to the literature (10%).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

[Thrombosis, immunology and drugs].

Diagnosis of thrombopenia due to heparin in sometimes false. We present a case with venous thrombosis in whom the suspicion of thrombopenia induced by heparin finally proved to be a quinidine induced lupus. Related to this observation we emphasise the importance of immunological investigation in patient with venous thrombosis.

Diagnosis, Differential↗
PubMed1991

Effects of soman-induced seizures on different extracellular amino acid levels and on glutamate uptake in rat hippocampus.

Extracellular amino acid levels in CA3 and CA1 fields of rat hippocampus, an area highly sensitive to seizures, were determined by intracranial microdialysis during seizures induced by systemic administration of soman (o-1,2,2-trimethylpropyl methylphosphonofluoridate), a potent inhibitor of acetylcholinesterase. The glutamate uptake level was determined on another series of animals in hippocampus homogenates. An early and transient increase in the extracellular glutamate level occurred in CA3 within 30 min of seizures, with correlated brief elevations of taurine, glycine and glutamine levels. The glutamate level increased early in CA1, declined and then became more sustained (after 50 min of seizures). Apparent elevations of taurine, glycine and glutamine levels in CA1 accompanied changes in glutamate concentrations. Changes of glutamate level correlated with an increase in the glutamate uptake which rapidly declined after 40 min of seizures. The role of the transient release of glutamate in CA3 and of the sustained release in CA1 in prolonged soman-induced seizures is considered. The correlation between glutamate and other amino acid release is studied.

Amino Acids↗
PubMed1991

Early dendritic changes in hippocampal pyramidal neurones (field CA1) of rats subjected to acute soman intoxication: a light microscopic study.

In rats poisoned with soman (s.c. 100 micrograms/kg), a potent inhibitor of cholinesterase (ChE), the numbers of dendritic spines of Golgi impregnated hippocampal pyramidal cells (CA1 sector) were evaluated within the first hour of the intoxication. Animals that experienced convulsions showed a rapid and striking decrease in the density of dendritic spines which could be reduced by nearly 80% of the controls in the basal dendrites 60 min post-soman exposure. Although the exact mechanisms cannot be determined from the present study, it is suggested that the spine loss may represent: (1) the first sign of the seizure-related neuronal changes which are known to occur later during soman intoxication; and (2) the expression of the 'dendrotoxic' effects produced by certain non-cholinergic excitatory transmitters such as glutamate.

Animals↗
PubMed1991

An assessment of temafloxacin in the treatment of chronic bacterial prostatitis.

Based on its in-vitro activity against the majority of organisms associated with bacterial prostatitis and its excellent penetration into prostatic tissue, prostatic secretions and seminal fluid, temafloxacin appears to be a suitable agent for the treatment of prostatic infections. The efficacy and safety of temafloxacin 400 mg bd for 28 days were assessed in 61 patients from ten centres in Germany with symptomatic bacterial prostatitis diagnosed by segmented localizing cultures. Urine and prostatic secretions were obtained for culture. Clinical signs and symptoms were evaluated at two weeks during treatment, and at 5 to 9 days and 26 to 30 days after treatment. Safety was monitored during and at the end of treatment. Escherichia coli and Enterococcus spp. were the most frequent pathogens. In 41 clinically and bacteriologically evaluable patients, 37 (90%) were successfully treated at 5 to 9 days; four of these patients did not return for follow-up at the final visit and the remaining patients (33) continued to be clinically cured or improved. Thirty-seven patients (90.2%) had eradication of pre-treatment pathogens at 5 to 9 days after treatment; three of these patients did not return for this final follow-up visit. There were six patients with persistent or recurrent pathogens isolated and six patients with reinfecting pathogens. Thus, 26 of 38 (68%) evaluable patients at visit 5 were free from infection (from either a pre-treatment pathogen or any subsequent new infecting pathogen) up to 26 to 30 days after treatment. One clinically evaluable but bacteriologically non-evaluable patient was classified as a therapeutic failure after nine days of treatment and was not included in the final assessment. Improvement in the severity of specific signs and symptoms was observed in greater than 90% of cases. Mild to moderate adverse events, mostly occurring during the first or second weeks of long-term therapy, were reported in 11.5% of patients. Temafloxacin 400 mg bd, for four weeks was very effective and well tolerated by the majority of patients with documented bacterial prostatitis.

Administration, Oral↗
PubMed1991

Pharmacokinetics of temafloxacin in humans after single oral doses.

Temafloxacin (A-63004) is a new quinolone antibacterial agent with a broad spectrum of activity against gram-positive and gram-negative aerobes and anaerobes. The pharmacokinetics and metabolism of temafloxacin were determined in healthy volunteers after administration of single oral doses of 100, 200, 400, 600, 800, and 1,000 mg. The corresponding peak concentrations in plasma (mean +/- standard deviation) were 0.98 +/- 0.26, 1.61 +/- 0.57, 2.43 +/- 0.56, 3.87 +/- 0.64, 4.54 +/- 1.03, and 6.67 +/- 0.74 micrograms/ml. The times that elapsed to attain peak levels ranged from 1.25 to 3.5 h. Statistical analyses of parameters related to the extent of absorption and the linearity of the dispositional pharmacokinetics detected no dose-related trends. Study-wide, total clearance (223 ml/min) and renal clearance (125 ml/min) showed low intersubject variability, with coefficients of variation near 20%. The terminal-phase rate constant of 0.090 +/- 0.008 h-1 corresponds to a half-life of 7.7 h. Temafloxacin was excreted mainly in the urine, with 57 +/- 11% of the dose appearing in the urine unchanged. Conjugated temafloxacin, oxidative metabolites, and conjugates thereof were minor components in urine, collectively accounting for 5 to 8% of the dose. Since intravenously dosed dogs eliminated 50% of the dose by nonrenal processes, urinary recoveries approaching two-thirds of the dose in humans were consistent with high, if not quantitative, absorption. Reported adverse events were generally mild, were randomly distributed between temafloxacin- and placebo-treated subjects, and were not dose related.

4-Quinolones↗
PubMed1991

Use of m-[131I]iodobenzylguanidine in the treatment of malignant pheochromocytoma.

The efficacy and safety of m-[131I]iodobenzylguanidine ([131I]MIBG) were assessed in 15 patients with malignant pheochromocytomas in a nonrandomized, single arm trial, in which patients were treated with [131I]MIBG (SA, 740 megabequerel/mg) every 3 months. Seven of these patients had bone and soft tissue metastases, 4 had only soft metastases, and 4 had only bone metastases. The follow-up period ranged from 6-54 months; the number of doses ranged from 2-11, with 2.9 (78.4 mCi) to 9.25 gigabequerel (GBq) (250 mCi)/administration and a cumulative activity from 11.1-85.90 GBq (300-2322 mCi). The absorbed cumulative dose in tumors ranged from 12-155 Gy. A beneficial effect of the treatment was observed in 9 patients (60%). No complete remission of the disease was observed. Seven patients died during the study, among whom 4 never responded to the treatment. Seven had hormonal responses (4 complete and 3 partial), with a duration ranging from 5-48 months. Among these patients, 4 relapsed, and 3 died within 3 months. Five patients had partial tumoral responses mainly located in soft tissues and for a duration ranging from 29-54 months. All patients with a hormonal response had objective improvement in clinical status and blood pressure. There was no clear-cut relationship between the cumulative dose and the responses. The main side-effect observed in 1 patient with widespread bone metastases after three doses (12.9 GBq) was a pancytopenia, which resolved after treatment was discontinued. This study suggests that repeated [131I]MIBG treatment could be effective in patients with advanced malignant pheochromocytoma.

3-Iodobenzylguanidine↗
PubMed1991

Involvement of the different rat hippocampal glutamatergic receptors in development of seizures induced by soman: an autoradiographic study.

Glutamate (GLU)-receptor subtypes, (quisqualate (QA)-, kainate (KA)-, N- methyl-D-aspartate (NMDA)-receptors) and the phencyclidine sites localized in the ion-channel associated to the NMDA-receptors, were studied by autoradiography in the hippocampus of rats subjected to a convulsive dose of the acetylcholinesterase inhibitor soman (0-, 1,2,2-trimethylpropyl methylphosphonofluoridate). In intoxicated rats, a significant increase in L-[3H]-GLU binding occurred within the first 40 min of seizures in the hippocampal CA3 and CA1 areas. Whereas binding to KA- and NMDA-receptors remained unchanged, L-[3H]-GLU binding to CA3 QA-receptors increased by 31 and 50% respectively after 10 and 40 min of seizures. In CA1, the change in QA-receptors was delayed (+30% after 40 min) and accompanied by an increase in the phencyclidine site binding capacity, reflecting the probable concomitant opening of NMDA ion-channels. These findings confirmed the previously suspected involvement of GLU in the earliest stages of soman-induced seizures, and suggested that, in hippocampus, the primary activation of QA-receptors in the CA3 region could lead to the secondary recruitment of combined non-NMDA (QA) and NMDA mechanisms in CA1.

Animals↗
PubMed1991

Ureterosigmoidostomy: reevaluation of a "forgotten" continent urinary diversion.

Between 1978 and 1983 we performed 19 ureterosigmoidostomies (25% of all urinary diversions). We try to realise a reevaluation of this technique by means of clinical data, laboratory findings, U.S.- and X-ray examinations. The mean follow-up time is 7.5 years. All patients mention a comfortable life-style. By routine administration of sodium bicarbonate, no electrolyte disturbances occur. Only 5 kidneys (on a total of 32 renal units) show major deformities. Colon carcinoma is not reported. Since the introduction of the ileal conduit by Bricker in 1950 (1), together with the repeatedly published higher incidence of colon carcinoma (2), a certain revulsion for the traditional Coffey-technique arose. Yet there are some important advantages in this peculiar surgical method. We think that, after a rather premature condemnation, the time is ripe for a reevaluation and a reevaluation of the ureterosigmoidostomy.

Aged↗
PubMed1991

[Involvement of glutamatergic system of amygdala in generalized seizures induced by soman: comparison with the hippocampus].

During seizures induced by soman, an organophosphorus compound, irreversible inhibitor of acetylcholinesterase, the intra-amygdaloid microdialysis of extracellular glutamate, an excitatory amino-acid, showed a sustained increase, more rapid than in hippocampus. This result suggests an early involvement of the amygdala in the development of soman-induced seizures. Moreover, the ex vivo, study by quantitative autoradiography of the binding of tritiated TCP (thienyl-phencyclidine) does not reveal an opening of ionic channels linked to N-methyl-D-aspartate (NMDA) sensitive receptors of glutamate, during seizures, unlike in the hippocampus. This difference could indicate, according to other experimental models, that in amygdala the release of glutamate could occur massively without repeated stimuli as in the hippocampus.

Amygdala↗