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C Lagarde

Publications and source records attributed to C Lagarde.

At least 19 recordsLinked to original sources

Risk of heparin lock-related bleeding when using indwelling venous catheter in haemodialysis.

BACKGROUND: The indwelling venous catheter such as Dual-Cath or Twin-Cath is widely used in haemodialysis. Although the manufacturer recommends filling the catheter lumen with heparin after the dialysis session to prevent clotting, little is known about the systemic effects of such a procedure. METHODS: Twenty haemodialysis patients with Dual-Cath were studied. Dialysis anticoagulation was achieved by injecting a bolus of dalteparin. The patient/control ratio of activated partial thromboplastin time (aPTT) was determined at the end of the session immediately before and 10 min after locking with 2 ml of undiluted heparin (10,000 U/catheter). We also determined the catheter volume for each patient and measured aPTT immediately before and 10 min after heparin locking with this patient-specific volume. Catheter patency was followed over a 2-week period. RESULTS: The aPTT values determined at the end of two consecutive dialysis sessions were nearly normal, respectively 1.29 (+/-0.17) and 1.33 (+/-0.22), whereas all patients had uncoagulable blood (aPTT >3.75) 10 min after locking with 2 ml of heparin. When catheter volumes were individually calculated, they were found to be substantially lower than 2.0 ml (1.21+/-0.12 for the arterial branch and 1.27+/-0.13 for the venous branch). aPTT was only 2.42+/-0.73 10 min after locking with the estimated volumes except in one patient (aPTT >3.75). No catheter clotting was observed despite these smaller locking volumes. CONCLUSIONS: A risk of inducing serious bleeding does indeed exist with Dual-Cath heparin locking, especially in postoperative patients. This risk can be reduced by measuring catheter length at the time of placement in order to ensure an appropriate lock volume. Sodium citrate, polygeline, or urokinase are possible alternatives to heparin.

Catheters, Indwelling↗

Structure of adeno-associated virus vector DNA following transduction of the skeletal muscle.

The skeletal muscle provides a very permissive physiological environment for adeno-associated virus (AAV) type 2-mediated gene transfer. We have studied the early steps leading to the establishment of permanent transgene expression, after injection of recombinant AAV (rAAV) particles in the quadriceps muscle of mice. The animals received an rAAV encoding a secreted protein, murine erythropoietin (mEpo), under the control of the human cytomegalovirus major immediate-early promoter and were sacrificed between 1 and 60 days after injection. The measurement of plasma Epo levels and of hematocrits indicated a progressive increase of transgene expression over the first 2 weeks, followed by a stabilization at maximal plateau values. The rAAV sequences were analyzed by Southern blotting following neutral or alkaline gel electrophoresis of total DNA from injected muscles. While a high number of rAAV sequences were detected during the first 5 days following the injection, only a few percent of these sequences was retained in the animals analyzed after 2 weeks, in which transgene expression was maximal. Double-stranded DNA molecules resulting from de novo second-strand synthesis were detected as early as day 1, indicating that this crucial step of AAV-mediated gene transfer is readily accomplished in the muscle. The templates driving stable gene expression at later time points are low in copy number and structured as high-molecular-weight concatemers or interlocked circles. The presence of the circular form of the rAAV genomes at early time points suggests that the molecular transformations involved in the formation of stable concatemers may involve a rolling-circle type of DNA replication.

Animals↗

[Allogeneic bone marrow transplantation in congenital erythropoietic porphyria. Gunther's disease].

INTRODUCTION: The congenital erythropoietic porphyria (Günther's disease) (CEP) is a rare autosomal recessively metabolic disease due to the deficit of uroporphyrinogen III cosynthetase, fourth enzyme of the porphyrin-heme biosynthesis. This disease is characterized by severe cutaneous photosensitivity with profound skin lesions, hemolytic anemia and excess of uroporphyrin I excretion. The vital prognosis is very bad and until now, no treatment seems to be efficient. Bone marrow transplantation seems to be able to correct the enzymatic deficit that causes the disease because it is located in the bone marrow. OBSERVATION: We report the case of a four and a half year old girl who received an allogeneic bone marrow transplantation (BMT) at the age of two. Despite an encouraging result, the first transplantation failed. A second allogeneic transplantation was attempted eight months later with the same HLA identical heterozygous donor and bone marrow engrafment succeeded. Twenty one months after the second bone marrow transplantation, clinical and biological results are still excellent. DISCUSSION: No classical treatment of CEP really proved its efficiency and no one was curative. CEP resulting from an homozygous deficiency in uroporphyrinogen III cosynthetase, enzyme that takes part in the porphyrin-heme biosynthesis which is principally located in the erythropoietic system of the bone marrow, substitution of this defective lineage by BMT was a very attractive treatment to correct this anomaly. The first bone marrow transplantation attempted on an affected child in 1990 in Manchester failed because the patient died of infections complications. After the failure of the first transplantation, our little patient is now healed twenty one months after the second BMT and biochemical anomalies are corrected. If a long follow up is necessary to appreciate the long-term efficiency of this treatment, allogenic bone marrow transplantation seems to cure Günther's disease and must be proposed as the treatment of this affection.

Bone Marrow Transplantation↗

Efficient and stable adeno-associated virus-mediated transduction in the skeletal muscle of adult immunocompetent mice.

Recombinant adeno-associated virus (rAAV) vectors were evaluated for gene transfer into the skeletal muscle of adult immunocompetent mice. A study using a vector encoding nuclear localized beta-galactosidase (rAAV-nls-lacZ) examined: (i) the efficiency and duration of transgene expression; (ii) the status of the AAV genome in the transduced fibers; and (iii) the possibility of improving gene transfer by inducing muscle regeneration. In the absence of regeneration, the injection of 1.7 x 10(7) particles in the quadriceps resulted in gene transfer to 10-70% of myofibers. Histological analysis indicated that the vector was able to reach myofiber nuclei distant from the injection point. Cellular infiltrates were absent at early time points but became conspicuous in the vicinity of some positive fibers at 4-8 weeks and subsided by 26 weeks. Southern analysis indicated that one to three copies of the vector genome were present per cell genome equivalent. They were associated with high-molecular-weight DNA in the form of tandem oligomers or interlocked circles. Gene transfer was not facilitated in the regenerating muscle. Rather, an early inflammatory response resulted in the elimination of most positive fibers after 8 weeks. The presence of regenerated fibers with beta-galactosidase-positive nuclei suggested that myoblasts had been transduced and were able to fuse to form new fibers. Gene transfer in the absence of immune reactions against the transgene product was studied by injecting mice with a rAAV carrying the murine erythropoietin (mEpo) cDNA. Dose-dependent elevation in the hematocrit was measured for over 200 days and corresponded to 5- to 20-fold increases in plasma Epo levels. We conclude that AAV vectors efficiently and stably transduce post-mitotic muscle fibers and myoblasts in vivo.

Animals↗

[Peritoneal dialysis in people more than 75 years old].

Over 75 years old peritoneal dialysis patients can be treated with at least as good results as those of hemodialysis. Peritoneal dialysis is the only method used to treat old patients at home with psychological profits. Regarding the lack of references on nutritional state of uremic old patients and on early death forecast factors geriatric peritoneal dialysis knowledges are not yet well established.

Aged↗

[Chylous ascites in 12 patients undergoing peritoneal dialysis].

Chylous ascites is a rare clinical entity often secondary to a lymphoma. In peritoneal dialysis even mild chylous ascites can cause cloudiness of the peritoneal effluent and thus lead to early diagnosis. Twelve cases of chylous ascites (defined by the presence of chylomicrons) among 230 patients with chronic renal failure treated in two peritoneal dialysis centers (Limoges and Saint-Pierre de la Réunion) are reported. A malignancy was encountered in only two cases (a B-cell lymphoma and an ovarian cancer). In the other cases, a precise diagnosis was difficult to establish and was only presumed. Thus chylous effusion in seven cases seemed secondary to cirrhosis, chronic pancreatitis, systemic amyloïdosis or cardiac failure. In three cases the cause was unknown, although microtrauma due to the Tenckhoff catheter was highly suspected. Chylous ascites lasted more than two years in four cases. The long-term nutritional consequences did not justify a change in the method of dialysis.

Adult↗

[Peritonitis in continuous ambulatory peritoneal dialysis: diagnosis and treatment].

Several antibiotic regimens to treat CAPD related peritonitis have been published. Some of them do not have any severe side effect. But they are efficient in less than 2/3 of the cases. Other treatments (2 antibiotics, one of them is an aminoglycoside) are more frequently efficient, but they seem to have severe ototoxicity. We propose the use of cephalosporins and quinolones for first line treatment of CAPD peritonitis. This regimen seem highly efficient without severe side effect.

Anti-Bacterial Agents↗

Subsequent development of acute non-lymphocytic leukemia in patients treated for Hodgkin's disease.

A nested case control study was carried out to investigate the association between treatment of patients with Hodgkin's disease (HD) and the risk of developing acute non-lymphocytic leukemia (ANLL). Seven Cancer Centers of the International Cancer Patient Data Exchange System of the UICC participated. A study cohort was selected consisting of 1,681 nonpretreated patients with HD, diagnosed from 1972 through 1978, and followed up through 1984. The median follow-up time was 66 months. Eighteen cases of leukemia were observed in the cohort. The risk of development of ANLL was significantly greater for male than for female patients. The treatment characteristics associated with an increased risk of developing ANLL were extensive radiotherapy, splenectomy and the chemotherapy combination of vincristine, procarbazine and mechlorethamine.

Acute Disease↗

[Treatment of peritonitis in kidney failure patients under continuous ambulatory peritoneal dialysis by pefloxacine. Results and pharmacokinetics].

Pefloxacin was used as monotherapy in 15 cases of peritonitis occurring in patients undergoing continuous ambulatory peritoneal dialysis (CAPD). Antibiotic administration was made intravenously on day 1 (800 mg) and from day 2 to day 4 (400 mg/day), then orally during 10 days (400 mg/day). The dosage of 400 mg gave a mean serum concentration peak (11.2 mg/l) and valley (5.4 mg/l) on the second day and a mean dialysate level of 5 mg/l. The last mean serum concentration (J14) were 5.5 mg/l (peak) and 2.5 mg/l (valley) and the mean dialysate level was 2.6 mg/l. Ten of these patients were cured. We explained pefloxacin therapy failure in two cases by resistant strains (S. sanguis and S. bovis), in one case by an acquired resistance during treatment (S. epidermidis), in an other case by catheter contamination; and in the last case, clinical failure occur despite good sensitivity with in vitro-test (Acinetobacter).

Adult↗

[Development of a knowledge-based system for aiding therapeutic decision in breast cancer].

The SENEX project has been initiated at the fondation Bergonié in 1985 and is intended for providing physicians in general hospitals with knowledge based systems for the management of cancer treatment protocols. The design and building of a knowledge-based system for the management of breast cancer protocols (SENEX) was the first goal of this project. SENEX has been developed using a commercially available development tool (Personal Consultant Plus, Texas-instruments) derived from EMYCIN. It runs on IBM and compatible microcomputers. The knowledge base embeds the formal knowledge contained in the breast cancer protocols currently in use at the fondation Bergonié, and some judgmental knowledge acquired form breast cancer experts. Production rules and frames allowed us to adequately represent and structure this knowledge and the problem solving processes related to the management of breast cancer. A preliminary informal evaluation of the system has shown that it performs at the expert-level in giving advice for patients included in formal protocols. Its use and acceptability are good. However, we have to add judgmental knowledge into the knowledge base and to interface the system with a temporal data base management system to improve the overall performances of SENEX. Moreover the effectiveness of the system remains to be demonstrated before one can anticipate is routine use in clinical practice.

Breast Neoplasms↗

Phase II trials of 5-FU, doxorubicin, and cisplatin in advanced, measurable adenocarcinoma of the lung and stomach.

A combination of 5-FU (600 mg/m2 on Days 1 and 8), doxorubicin (40 mg/m2 on Day 1), and cisplatin (75 mg/m2 on Day 1) has been used for treatment of 31 patients with advanced measurable adenocarcinoma of the lung and 35 with gastric cancer. The regimen was given every 4 weeks until disease progression to patients who had not received prior chemotherapy. One complete response occurred in the lung cancer group. Ten of the gastric cancer patients (29%) had partial responses. The median duration of response was 5.5 months and the median survival in responding patients was 10.8 months. Toxicity of the regimen was moderate. We conclude that this combination offers no particular advantages over previously described treatments for these diseases.

Adenocarcinoma↗

[Metastatic cancer of the prostate: phase II study of spirogermanium (NSC 192965)].

A phase II study of spirogermanium was conducted in a series of 15 patients with metastatic prostatic carcinoma. All the patients have previously received multiple hormonal therapies. The drug was administered at the dose of 200 mg/m2 by a continuous infusion for five days, and 120 mg/m2, three times a week subsequently. The side effects were mainly neurological toxicity and phlebitis at the injection points which were dose and schedule dependent. Only one partial response for two months was noted in this series. Thus, spirogermanium seems to have a limited value in patients with prostatic cancer.

Aged↗