[Severe parietal cellulitis following laparoscopy for peritonitis caused by perforated duodenal ulcer].
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Cellulitis↗
Biomedical subjects
Y Le Roux
Publications and source records attributed to Y Le Roux.
Proteolysis in samples of quarter milk with varying somatic cell counts. 1. Comparison of some indicators of endogenous proteolysis in milk.
Eighty-six samples of quarter milk from 31 cows, the mean SCC of which exceeded 400,000 cells/ml, were analyzed for SCC, chloride content, pH, clotting time, total N, soluble N, casein N, proteose-peptone content, plasmin activity, and amount of free NH2 groups, parameters that are related to the udder health condition and to the deterioration of the protein quality. Analysis of the milk from each quarter separately improved the correlations considerably compared with analyses of samples from all 4 quarters mixed together. Measurement of free NH2 groups, using the 2, 4, 6-trinitrobenzene sulfonic acid, was not appropriate for estimating the extent of protein deterioration in milk samples with different SCC. Unlike SCC, the proteolysis index, plasmin activity, and the proteose-peptone content were highly correlated themselves and with most of the parameters related to proteolysis in milk. Proteolysis occurred in milk samples with SCC as low as 250,000 cells/ml. The quality of milk protein decreased unavoidably during lactation, regardless of SCC.
Amides↗
Proteolysis in samples of quarter milk with varying somatic cell counts. 2. Component PP3 and beta-casein-1P (f29-105 and f29-107) of the proteose-peptone fraction.
The proteose-peptone fraction was studied to measure proteolysis in 86 samples of quarter milk from 31 cows with subclinical mastitis. The relative content of component PP3 decreased significantly in the total of proteose-peptone as plasmin activity increased, but the content of this component in milk was not correctly correlated with the plasmin activity (r = .52). Electrophoresis, amino acid composition, and sequence analysis showed that the component beta-CN-1P (f29-105/7) of the proteose-peptone fraction was a terminal product of plasmin-like activity and was located correctly electrophoretically. Correlation factors between the plasmin activity and content in milk of component beta-CN-1P (f29-105/7) was very high (r = .87). This component could be used as indicator of the endogenous proteolysis in milk from cows with subclinical mastitis.
Amino Acid Sequence↗
Comparison of the pharmacokinetic profiles of three low molecular mass heparins--dalteparin, enoxaparin and nadroparin--administered subcutaneously in healthy volunteers (doses for prevention of thromboembolism).
The present trial was designed to comparatively investigate the pharmacokinetic profile and evaluate the apparent bioavailability pattern of three already marketed low molecular mass heparins (LMMHs): dalteparin (Fragmin), nadroparin (Fraxiparin), and enoxaparin (Lovenox) given by subcutaneous route. The study was carried out in 20 healthy young volunteers given, according to a cross over design, a single subcutaneous injection of the doses recommended for the prophylaxis of deep vein thrombosis (commercial preparations, prefilled syringes): dalteparin 2,500 IU (= 2,500 IU anti-Xa), nadroparin 7,500 ICU (= 3,075 IU anti-Xa), enoxaparin 20 mg (= 2,000 IU anti-Xa) and enoxaparin 40 mg (= 4,000 IU anti-Xa). Of the markers used, activated partial thromboplastin time (APTT), thrombin clotting time (TCT), Heptest, anti-thrombin (aIIa) activity and anti-Xa (aXa) activity, the most pertinent parameter (from a biodynamic viewpoint) is plasma aXa activity. We demonstrated that dalteparin, nadroparin and enoxaparin exhibit statistically significantly different pharmacokinetic and overall disposition patterns. Normalized to the same injected dose (1,000 IU aXa), the relative actual amount of plasma anti-Xa activity generated by enoxaparin is 1.48 times greater (p < 0.001) than that of nadroparin and 2.28 times greater (p < 0.001) than that of dalteparin while the plasma amount induced by nadroparin is 1.54 times greater (p < 0.001) than that of dalteparin. The apparent total body clearance of enoxaparin doses (CL/F = 16.7 +/- 5.5 and 13.8 +/- 3.2 ml/min) is significantly smaller than those of nadroparin (CL/F = 21.4 +/- 7.0 ml/min; p < 0.01) and dalteparin (CL/F = 33.3 +/- 11.8 ml/min; p < 0.001) while dalteparin apparent clearance is about 1.5-fold greater (p < 0.001) than that of nadroparin. These LMMHs also differ by their renal excretion pattern: more fragments exhibiting an anti-Xa activity are recovered in urine following enoxaparin doses (6.4 and 8.7% of the dose, respectively) than following nadroparin (3.9%) and dalteparin (3.4%) injection. These differences in the disposition profiles explain why the apparent elimination half life t1/2 values of the LMMHs compared here are different: dalteparin: 2.8 h; nadroparin: 3.7 h; and enoxaparin: 4.1 h. Whether or not these differences may contribute to explain the different safety/efficacy balance of each of these antithrombotic medications remains to be discussed and needs further studies.
Adolescent↗
[Place of celio-video-surgery in splenectomy for hematologic diseases].
In order to evaluate the place of the laparoscopic approach in splenectomy for haematological disease, the authors prospectively studied a series of 25 consecutive patients requiring splenectomy. There were 11 cases of thrombocytopenic purpura, 9 lymphomas, 2 cases of herediary spherocytosis, 1 Felty syndrome, 1 idiopathic myelofibrosis and 1 Hodgkin disease. Twelve patients (48%) underwent an immediate conventional procedure for huge splenomegaly (10), obesity (1), unavailability of video-equipment. Thirteen patients (52%) underwent a laparoscopic approach. Five of these operations were converted into a conventional approach for various reasons. In the other 8 patients, the spleen was completely released laparoscopically. In two of these 8 patients, the spleen was removed via a sub-pubic Pfannenstiel incision due toits volume. The last 6 spleens (24%) were removed in a plastic bag, corresponding to 5 cases of one thrombocytopenic purpura and one Hodgkin disease. None of these patients were obese. These results suggest that the laparoscopic approach is indicated in case of moderate splenemegaly in non-obese patients.
Adult↗
[Celioscopic treatment of perforations of duodenal ulcers. 6 cases].
Traditionally, perforations of duodenal ulcers are managed by suturing followed by peritoneal lavage and the underlying cause is addressed secondarily. Laparoscopy provides a means of meeting the different therapeutic needs. From May to October 1993, we treated 6 consecutive perforations of duodenal ulcers laparoscopically. In 5 cases, the perforation was the first manifestation of acute duodenal ulceration and the other case was chronic. The laparoscopic operation included peritoneal lavage and simple suture of the ulcer. The immediate post-operative period was uneventful. With a current follow-up of 3.6 months, 5 patients are asymptomatic and ulcer cicatrization has been confirmed by fibroscopy. In the sixth case with a past history of chronic duodenal ulcer, re-operation was required after a delay of 2 months for acido-fundic vagotomy (performed laparoscopically). The local presentation was satisfactory in this patient. Extensive peritoneal lavage, which can be performed with laparoscopy together with suture when the ulcer is recent, allows managing such patients according to Taylor's method. The usefulness of vagotomy can then be addressed and performed later laparoscopically after the initial lavage. This new approach offers a means of complete cure and has all the advantages of the classical technique.
Acute Disease↗
[Laparoscopic reduction and fixation of volvulus of the stomach].
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Aged↗
[Pelvic lymphoceles after kidney transplantation. Intraperitoneal marsupialization by celioscopy].
OBJECTIVES: The appropriate treatment for symptomatic pelvic lymphoceles occurring after renal transplantation is still debated. External drainage exposes to risk of recurrence, infection or graft sclerosis and laparotomy has been required for intraperitoneal marsupialization in patients at risk. We report our experience with two cases treated by laparoscopic intraperitoneal marsupialization. PATIENTS: From November 1986 to September 1992, 170 renal transplantations were performed at our University Hospital. Lymphoceles developed in 12 cases and percutaneous puncture and irrigation was performed in all, successfully in 10. Relapse occurred in 2 patients--one 50-year-old woman with chronic glomerulonephritis and one 41-year-old man on peritoneal dialysis for polycystic renal disease--recipients of cadaver kidneys. SURGICAL TECHNIQUE: The laparoscopy was conducted under general anaesthesia. Four trocars were inserted, a 10 mm via the umbilicus for the optical system and three 5 mm trocars via the right and left flank and the left iliac fossa. A long puncture needle was used to drain the lymphocele and a localized collection and a large peritoneal window was created. The abdominal cavity was abundantly washed before withdrawing. RESULTS: Operation time was 35 minutes and conversion to laparotomy was not required. The only complication was a haematoma at one insertion site. Patients were discharged on day 2 and on day 1 with an unchanged immunosuppressor regimen. At 10 months follow-up, the patients were symptom-free and echography was normal. CONCLUSIONS: Surgical treatment of lymphoceles can be successfully performed by laparoscopy. The choice between conservative treatment and laparoscopic surgery remains to be determined.
Adult↗
Pharmacokinetics of sparfloxacin in humans after single oral administration at doses of 200, 400, 600, and 800 mg.
The pharmacokinetics of sparfloxacin at oral doses of 200, 400, 600, and 800 mg were studied in 12 healthy volunteers in a randomized double-blind crossover study. Each dose administration was separated by a 1-week washout period. Plasma and urine samples were collected up to 120 hours postdosing, for determination of free and total (free plus glucurono-conjugated) sparfloxacin levels by high-performance liquid chromatography assay and ultraviolet detection. Mean Cmax values ranged from 705 +/- 158 to 1966 +/- 620 ng/mL for the 200 to 800 mg doses, at median tmax ranging from 4 to 5 hours. A slight decrease of sparfloxacin bioavailability with increasing dose was observed because AUC was 87% to 88% of the expected area when the dose was doubled. The elimination half-life values were constant over the dose range (with values ranging from 18 to 21 hours) as well as the renal clearance. The metabolic ratio conjugated/free drug was not modified by increasing dose.
Administration, Oral↗
Pharmacokinetics and suction blister fluid penetration of a semisynthetic injectable streptogramin RP 59500 (RP 57669/ RP 54476).
RP 59500 is a new semisynthetic injectable streptogramin with excellent activity against most gram-positive bacteria. In order to assess its potential for the treatment of tissue infections, the pharmacokinetics and penetration into suction blister fluid were studied in a pilot phase I study in six male volunteers following a single infusion of 12 mg/kg over 1 h. Plasma and suction blister fluid concentrations were determined by microbiological assay. The mean peak concentration in plasma was 8.65 mg/l at the end of infusion. The mean plasma elimination half-life was 1.48 h. The mean peak concentration in interstitial fluid was 2.41 mg/l and was reached after 1 h in two volunteers and after 2 h in the other four. The mean percentage penetration for the interval 0-6 h was 82.5%. RP 59500 was still detectable in interstitial fluid at 6 h at a mean concentration of 0.92 +/- 0.25 mg/l. The data of this pilot study demonstrate good penetration of RP 59500 into non-inflammatory interstitial fluid.
Adult↗
Pharmacokinetics of sparfloxacin in patients with renal impairment.
The pharmacokinetics of sparfloxacin were studied in 14 renal failure patients (group I, 7 with creatinine clearance of > 10 to 30 ml/min; and group II, 7 with creatinine clearance of < or = 10 ml/min) after a single oral dose of 400 mg. Plasma and urine samples were collected up to 144 h postdosing for determination of parent and total (parent-plus-glucuronide-conjugated) sparfloxacin levels, by high-pressure liquid chromatography assay and UV detection. The elimination of the drug in patients compared with that in healthy volunteers was markedly impaired. The mean elimination half-lives of sparfloxacin were 34.9 and 38.5 h in group I and group II, respectively, versus 19.1 h in healthy volunteers. Conjugated drug half-lives were 23.7, 35.0, and 15.3 h, respectively. The renal clearance of the drug was markedly reduced in the patients, with values of 6.8, 4.8, and 21.2 ml/min determined for group I, group II, and healthy subjects, respectively, for parent sparfloxacin and with values of 31.5, 14.0, and 327 ml/min for conjugated sparfloxacin. The nonrenal clearance of sparfloxacin was moderately, but not significantly, decreased in group II renal failure patients. No difference between the two groups of patients was detected in sparfloxacin levels in plasma. A significant relationship between pharmacokinetic parameters and creatinine clearance was observed only for renal clearance of parent or conjugated sparfloxacin.
Adult↗
Evaluation of Bayesian estimation in comparison to NONMEM for population pharmacokinetic data analysis: application to pefloxacin in intensive care unit patients.
The pharmacokinetics of pefloxacin (PF) were investigated in a population of 74 intensive care unit patients receiving 400 mg bid as 1-hr infusion using (i) Bayesian estimation (BE) of individual patient parameters followed by multiple linear regression (MLR) analysis and (ii) NONMEM analysis. The data consisted of 3 to 9 PF plasma levels per patient measured over 1 to 3 dosage intervals (total 113) according to four different limited (suboptimal) sampling 3-point protocols. Twenty-nine covariates (including 15 comedications) were considered to explain the interpatient variability. Predicted PF CL for a patient with median covariates values was similar in both BE/MLR and NONMEM analysis (4.02 and 3.92 L/hr, respectively). Bilirubin level and age were identified as the major determinants of PF CL by both approaches with similar predicted magnitude of effects (about 40 and 30% decrease of median CL, respectively). Confounding effects were observed between creatinine clearance (26% decrease of PF CL in the BE/MLR model), simplified acute physiology score (a global score based on 14 biological and clinical variables) (18% decrease of median CL in the NONMEM model) and age (entered in both models) which were highly correlated in our data base. However, both models predicted similar PF CL for actual subpopulations by using actual covariate values. Finally, the NONMEM analysis allowed identification of an effect of weight on CL (decrease of CL for weight < 65 kg) whereas the BE/MLR analysis predicted an increase of CL in patients treated with phenobarbital. In conclusion, both approaches allowed identification of the major risk factors of PF pharmacokinetics in ICU patients. Their potential use at different stages of drug development is discussed.
Adolescent↗
Comparative bioavailability study of cefixime administered as tablets or aqueous solution.
The relative bioavailability of cefixime was studied in 24 healthy male volunteers, with each subject receiving a single 400mg dose of cefixime administered as an aqueous solution, a 400mg tablet and two 200mg tablets, in a randomised crossover sequence. Serum and urine samples were analysed using high-performance liquid chromatography. Peak cefixime levels were achieved 3 hours after administration of the solution vs 4 hours for the 2 tablet formulations; however, the extent of absorption was only slightly improved with the solution (by 14 and 7% compared with the 1 x 400 and 2 x 200mg tablets, respectively). The 400mg and 2 x 200mg tablets were found to be bioequivalent. The pharmacokinetic profile of the 400mg cefixime tablet (mean maximum plasma concentrations of 4.4 mg/L at 4 hours, area under the concentration-time curve of 34.4 mg/L.h, and apparent terminal elimination half-life of 3.7 hours) supports the clinical evaluation of a 400mg once-daily dosage regimen for cefixime.
Adult↗
Evaluation of Bayesian estimation to discriminate subpopulations of patients with altered pharmacokinetics using fragmentary data: a pilot study with pefloxacin.
Bayesian estimation of individual pefloxacin pharmacokinetic parameters was evaluated in patients with renal (n = 34) or hepatic (n = 16) impairments who participated in experimental pharmacokinetic studies during pefloxacin development. The trials involved singly intravenous dosing (300 to 850 mg as 0.5 to 1h-infusion) and serial pefloxacin plasma level measurements (n = 10-18 over 72-96 h). Bayesian estimation used only 2 measured plasma levels (end of infusion and either 12 hour (BE 12h) or 48 hour (BE 48h) levels) and a priori information obtained in a reference population of healthy volunteers (n = 19). The performance of Bayesian estimation in predicting total plasma clearance (Cl), elimination half-life (t1/2) and steady state volume of distribution (Vss) was evaluated with respect to weighted nonlinear least-square estimates using all the data points and a two-compartment model. Pharmacokinetic parameters (and their inter-individual variability) in patients differed significantly from those of healthy volunteers (e.g. t1/2 of 22 +/- 14 h, range 6-81 h vs. 11 +/- 2 h, range 8-17, p less than 0.001). BE 12h provided biased estimates of Cl and t1/2 (24 and 28% respectively) and poor precision (30 and 53% respectively), Vss being well estimated. The BE 48h estimator had good performance with unsignificant bias (less than 1%) and good precision (extremes 13 and 27% for Cl and t1/2 respectively). Patients with hepatic impairment had the more pronounced pharmacokinetics modifications and could even be discriminated from healthy volunteers using the biased BE 12h estimates. These results suggest that Bayesian estimation is quite robust to the a priori information.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
[Complicated solitary biliary cysts].
With development of ultra sound, solitary hepatic cyst (SHC) appears as a common and benign affection. Complications can occur in 10 per cent of cases. We report here four cases of complicated SHC: vena caval obstruction, intracystic bleeding, rupture, intracystic infection. Those four patients were successfully treated by partial excision of the cyst in the first 3 cases, and by percutaneous drainage with CT scan guidance in the latter. Complications of SHC occur only in large cysts, with a diameter up to 8 cm. So, small SHC do not require any treatment, while large SHC must be treated to avoid complications. Percutaneous aspiration and direct injection of alcohol can lead to recurrence. Surgical therapy by partial excision is successful, with low rates of mortality and morbidity.
Adolescent↗
[Role of coloproctectomy with colonic-anal anastomosis in the treatment of rectal cancer].
The aim of this study was to determine the efficacy and long term results of straight colo-anal anastomosis (CAA) after resection for rectal carcinoma as described by Parks. From January 1986 to June 1989, 40 patients underwent this operation: 27 men and 13 women with a mean age of 63.5 years (range 37-81). In 36 cases, the indication was for carcinoma of mid and low rectum and in 4 cases for carcinoma of the upper rectum associated with a low rectal benign tumour (3 Dukes A, 19 Dukes B, 13 Dukes C, and 5 Dukes D). A diverting colostomy was constructed in all cases. Operative mortality was one patient (2.5 per cent) by pulmonary embolism. Anastomotic dehiscence occurred in four patients. None of these patients required reoperation and all colostomies have been closed. 6 patients presented a local recurrence (15.4 per cent) 6 to 34 months after CAA, of whom two were treated by abdomino-perineal resection. 5 patients died 6 to 34 months after CAA from local recurrence (2 cases) or distant metastasis (3 cases) and one patient has liver disease. All others patients are alive free of disease with a mean follow-up of 21.7 months (range 3-46 months). Actuarial survival is 77 per cent at 40 months. Functional results were assessed in the 26 patients followed up more than one year. The mean stool frequency was 2.4 per day (range 0, 3-6). All patients are continent, with a good discrimination gas-stool. 4 patients (15.4 per cent) suffer from soiling, 5 (19 per cent) from stool frequency, and 2 (7.7 per cent) from urgency. In conclusion, CAA is a good alternative of abdominoperineal resection for some mid and low rectal carcinomas. Functional results might be improved by the construction of a colonic reservoir.
Adenocarcinoma↗
The antithrombotic activity and pharmacokinetics of enoxaparine, a low molecular weight heparin, in humans given single subcutaneous doses of 20 to 80 mg.
The pharmacokinetics of enoxaparine, a low molecular weight heparin, was randomly studied in 12 healthy male volunteers. Doses of 20, 40, 60, and 80 mg were injected subcutaneously in randomized cross-over fashion. Anti-IIa and anti-Xa activities (using amidolytic methods), and calcium thrombin time, were measured over 36 hours. The maximum Amax of the anti-IIa and anti-Xa activities appeared 3 to 4 hours after administration. The terminal half-lives of anti-IIa and anti-Xa activities were approximately 2 and 4 hours, respectively, with no significant variation between the different doses. For the anti-Xa activity, there was a highly significant positive correlation between the dose injected and individual values of Amax (r = +0.915; P less than .001) and AUC (r = +0.913; P less than .001). Enoxaparine displays a relatively small apparent volume of distribution (about 7.0 L) and its total body clearance is about 1.25 L/hr. The mean residence time ranges from 4.6 to 7.6 hours. Thus, the pharmacokinetic profile of enoxaparine is characterized by a linear relationship between dose and absorption, a relatively low clearance and long elimination half-life, and a high anti-Xa/anti-IIa ratio.
Adult↗
Pharmacokinetics of spiramycin in man.
The pharmacokinetics of spiramycin were studied after single and repeated administration by iv and oral routes. Following iv administration of a 500-mg dose in a one-hour infusion, peak serum concentrations were 1.54-3.10 mg/l. These concentrations are higher than MICs of spiramycin for various infectious agents. Eight hours after the end of infusion, the mean serum concentration was close to 0.25 mg/l. Spiramycin is rapidly and widely distributed throughout the body and achieves high ratios of tissue to serum concentrations in bucco-dental, pulmonary and prostatic tissues and skin. The distribution half-life of spiramycin was 10 min. The steady-state volume of distribution (Vdss) and the tissue distribution volume were 5.6 and 4.5 l/kg. The absolute bioavailability of spiramycin was 36% (S.D. +/- 14). Oral doses of spiramycin between 1 and 2 g resulted in linear increase in the peak serum levels and areas under the serum concentration-time curve. Spiramycin does not appear to undergo important metabolic conversion and is mainly excreted via the biliary route. Indeed, in man, the urinary excretion of active compounds represents only 7.6 to 20% of the administered dose. Spiramycin had a terminal elimination half-life of approximately 5 h. Renal clearance (144 ml/min) was much lower than non-renal clearance (887 ml/min). The total body clearance of spiramycin in young adults was 1.42 l/min (S.D. +/- 0.5) but only 0.53 l/min (S.D. +/- 14) in elderly subjects. During repeated iv administration (500 mg tid), steady state was achieved after four doses. Cmax and Cmin were 3.0 and 0.5 mg/l in young adults and 4.5 and 1.75 mg/l in elderly patients. Spiramycin's kinetics differ in several important respects from erythromycin's, notably the larger volume of distribution of spiramycin which reflects the higher tissue concentration. The reduced spiramycin clearance in elderly subjects requires further investigation.
Administration, Oral↗