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Biomedical subjects

M Lacombe

Publications and source records attributed to M Lacombe.

At least 37 records · Page 2Linked to original sources
PubMed1995

Exploring the role of histidines in the catalytic activity of duck delta-crystallins using site-directed mutagenesis.

The duck delta 2-crystallin gene encodes an enzymatically-active argininosuccinate lyase while the delta 1-crystallin gene product, although 94% identical, is enzymatically inactive. Four histidine residues in the duck delta 2-crystallin. His91, His110, His162 and His178, were converted to asparagine residues in an effort to define the role of histidines in the catalytic process of this enzyme-crystallin and to explain the lack of enzyme activity in the delta 1-crystallin protein. The recombinant mutant proteins were expressed in E. coli and purified to homogeneity for analysis. These four residues were chosen because they fall within highly conserved regions of argininosuccinate lyases from several species. This analysis revealed that change of His91 or His162 for asparagine resulted in complete loss of activity. The His110 enzyme had a reduced Vmax and the His178 enzyme was near normal in its kinetic properties. These data confirm the roles of histidine in the catalytic process of this enzyme-crystallin and suggest that the change of His91 to Gln91 observed in the duck and chicken delta 1-crystallin molecules may be sufficient to account for the lack of enzymatic activity of those proteins.

Amino Acid Sequence↗
PubMed1995

[Aneurysms of the renal artery].

A retrospective study of the patients operated on for renal artery aneurysm by a single surgeon during a 30-year period was undertaken. The author's experience amounts to 123 patients of whom 74 were females (60%) and 49 males (40%). The average age of the patients was 42.8 years. Preoperative investigations included usual tests of renal function, radiological investigations (fig. 4 and 5) and especially renal arteriography and study of the repercussions of arterial hypertension when present. In most cases (90%) these aneurysms were of fibrodysplastic origin. Acquired or postoperative aneurysms accounted for only 10% of cases. Dysplastic aneurysms are usually saccular with a fibrous neck and are located at or near an arterial bifurcation (fig. 1); they may have a very thin wall that explains the possible occurrence of rupture; intrasaccular thrombosis is very rare and so are embolies in the kidneys. Associated lesions are present in about two thirds of the patients (table I) and require a complete evaluation before surgery: lesions of the renal artery (segmental stenosis or diffuse fibromuscular hyperplasia) are the most frequent (fig. 2 and 3); other arteries either in the abdomen (aorta, splenic) or in distant territories (carotid) may also exhibit pathologic changes, particularly aneurysms; lesions of the kidney(s) and/or of the urinary tract may also be observed. In 80% of patients, the aneurysms were discovered on angiography performed because of arterial hypertension. But 20% of the patients were strictly normotensive. On account of bilateral repairs, 128 operations were performed: 17 nephrectomies and 111 vascular reconstructions. The main indication for nephrectomy was severely damaged kidneys. Vascular repair is the ideal treatment and various techniques may be used depending on anatomical arrangement of the vessels (table II). Ex situ surgery was performed in 29% of patients. Use of an arterial substitute is optional; when it appears necessary, arterial autografts are always preferable because they do not undergo late degenerative changes with time. The morbidity of surgical treatment is low. Evolution of arterial blood pressure after surgery leads to think that aneurysms of the renal artery cannot be held responsible for arterial hypertension: whenever a stenosis of the renal artery is associated, hypertension is of renovascular origin and is constantly cured or improved after surgery; in other patients, arterial hypertension remains unchanged after repair of the aneurysm, suggesting that hypertension is essential and simply coexists with the aneurysm without relationships of cause and effect between them. Surgery prevents the occurrence of ruptures as well and gives long term satisfactory anatomical results (fig. 6). Surgery is indicated in most cases and especially in young women (because of the risk of rupture during pregnancy) and in aneurysms exceeding 2 cm in diameter.

Adolescent↗
PubMed1994

Ex situ repair of complex renal artery lesions.

A total of 59 patients (from a personal series of 354) underwent ex situ repair of complex renal artery lesions. This series comprised 27 males and 32 females, of whom 15 were children and 44 adults, with ages ranging from 17 months to 70 years. The operated lesions were aneurysms with or without associated stenosis, spontaneous dissection, extensive fibrodysplasia and reoperations on the renal artery. In all patients, the kidney was exteriorized and cooled by perfusion of cold Collins' solution. The kidney was reimplanted after repair in either the loin or the iliac fossa. An arterial substitute was used in 42 patients. No mortality was observed. There were three cases of postoperative thrombosis of the repaired artery. Segmental thrombosis leading to partial atrophy of the kidney occurred in three patients. During long-term follow-up, one repeat stenosis and two fusiform dilatations of the venous autografts were observed. All other repairs (85%) were successful. Arterial hypertension in 46 patients was cured in 33 cases (72%) and improved in eight (17%). Renal function was improved after repair of severe stenotic lesions impairing renal blood flow restored normal circulation to the organ. Ex situ repair must be reserved for: (1) multiple lesions involving terminal branches of the renal artery for which prolonged circulatory arrest is required; and (2) lesions profoundly situated in the renal sinus that are difficult to treat by conventional surgery.

Adolescent↗
PubMed1994

[Femoral arteriovenous fistulas after vascular puncture for hemodialysis].

From 1978 to 1991 we observed 10 patients who developed femoral arteriovenous fistula after venous puncture for hemodialysis. The fistula most often appeared after several punctures, but 3 developed after a single puncture. Diagnosis was made on the basis of local observation and auscultation of the vessel (bruit + thrill n = 10, hematoma n = 4, pulsatile mass n = 1). Two patients had arteriography and 2 had echo-doppler. Arteriography was not required for diagnosis (since clinical signs were sufficient), or for treatment, since echo-doppler and surgery indicated the location of the fistula. Five patients underwent surgery. In all cases, continuity of the main vessels of the lower member was maintained or reestablished during surgery. Surgery is mandatory for high flow rate. Such fistulas cannot be used and can cause cardiac failure in patient with another fistula for hemodialysis. Surgery should not be undertaken too early because of the possibility of spontaneous clotting (particularity if echo-doppler shows low flow rate), and to allow organization of the lesions and easier dissection. Auscultation of the vessel should be a routine procedure after any femoral vein puncture in order that this complication not be overlooked.

Adult↗
PubMed1994

[Simultaneous reconstruction of the abdominal aorta and renal arteries].

Twenty-six patients underwent simultaneous reconstruction of the abdominal aorta and renal artery on one or both sides, for a total of 31 renal artery repairs. There was no postoperative mortality in the current series. Blood pressure control (with or without antihypertensive treatment) was obtained in 88% of cases. In patients with renal failure, improvement of renal function occurred in 60% of cases. Results obtained in this series show that surgical repair of aorta and renal artery (ies) can be undertaken with low operative risk. It appears to be a safe procedure and gives satisfactory results.

Adult↗
PubMed1993

Acute graft-versus-host disease prophylaxis with methotrexate and cyclosporine after busulfan and cyclophosphamide in patients with hematologic malignancies.

The combination of two powerful immunosuppressive agents, methotrexate (MTX) and cyclosporine (CSP), has resulted in a significant decrease in the morbidity and mortality after allogeneic bone marrow transplantation (BMT). However, the additive toxicities from ablative preparative regimens may lead to suboptimal use of this combined immunoprophylaxis. We evaluated the efficacy and feasibility of administering MTX/CSP with busulfan (4 mg/kg/d for 4 days) and cyclophosphamide (50 mg/kg/d for 4 days) (BuCy4) in 101 consecutive patients with hematologic malignancies categorized into high- and low-risk groups receiving HLA-matched marrow grafts. Postgrafting immunosuppression consisted of MTX short course (15 mg/m2 on day 1 and 10 mg/m2 on days 3, 6, and 11) and intravenous CSP (1.5 mg/kg every 12 hours). Eighty-three patients (82.1%) received 100% of MTX calculated dose and 87 (86.1%) achieved a CSP therapeutic level (250 to 600 ng/mL) within a median of 16 days. Seventy-three patients (72.2%) received optimal immunosuppressive therapy comprising a full MTX course and achieving CSP therapeutic concentrations. The Kaplan-Meier estimated incidence of grade II to IV acute graft-versus-host disease (GVHD) was 9.2% for all patients and 5.5% in patients receiving optimal GVHD prophylaxis. Eighty-nine patients (88.2%) survived > or = 100 days posttransplant and 43 (48.3%) developed chronic GVHD, the majority of which were de novo (31 of 43). The estimated incidence of relapse was 28.9% for all patients and 14.8% in the low-risk group, with a median follow-up of 24.5 months. High-risk features and the absence of chronic GVHD were significantly associated with relapse (P = .002 and .036, respectively) in multivariate analyses. Projected disease-free survival at 2 years was 52.3% for all patients and 65.2% in low-risk patients. Disease-free survival was significantly improved in optimally treated patients (P = .03) due to a lower incidence of early deaths from acute GVHD and infectious episodes. In conclusion, optimal delivery of MTX/CSP in association with BuCy4 resulted in a near complete abrogation of acute GVHD in HLA-matched transplants and a significantly improved disease-free survival.

Adult↗
PubMed1993

Allogeneic bone marrow transplantation following busulfan-cyclophosphamide with or without etoposide conditioning regimen for patients with acute lymphoblastic leukaemia.

We have investigated the feasibility and efficacy of administering a radiation-free preparative regimen in the setting of allogeneic bone marrow transplantation (BMT) in 40 consecutive patients with acute lymphoblastic leukaemia (ALL). Busulfan (4 mg/kg/d x 4 d) and cyclophosphamide (50 mg/kg/d x 4 d) (BuCy4) were given in 29 patients and 11 received busulfan (4 mg/kg/d x 4 d), etoposide (60 mg/kg) and cyclophosphamide (60 mg/kg/d x 2 d) (BuCy+VP - 16). Median age was 22 years (range 1-50); 11 patients were children < or = 15 years of age. All children and 20 adults were at high risk of relapse pretransplant. Nine adults and one child died from transplant-related toxicity. 11 patients relapsed at a median of 11 months post-transplant (range 2-27). The 3-year Kaplan-Meier estimated probability of relapse was 42.1% and found to be significantly lower in patients with chronic GVHD (P = 0.03). 19 patients are leukaemia-free survivors with a median follow-up of 33 months (range 7-59). The Kaplan-Meier actuarial probability of disease-free survival at 3 years was 43% for all patients. 63.6% for children versus 30.2% for adults (P = 0.24) and 51.6% for patients transplanted in first remission versus 30.2% for those transplanted in subsequent remissions (P = 0.20).

Adolescent↗
PubMed1993

[Digital arterial embolism after thrombosis of arteriovenous fistula].

Four patients suffering from severe digital ischemia due to emboli originating from a thrombosed arteriovenous fistula were operated on. In all cases, a large aneurysm had developed on the efferent vein. Segmental resection of the fistula and of the aneurysm with or without reanastomosis of the artery was successfully performed in all patients; a thoracic sympathectomy was performed in one because of the severity of the ischemic symptoms. Progressive degenerative changes of the arterialized vein account for the development of an aneurysm at its level with secondary thrombosis. When performing an arteriovenous fistula, end-to-end or end-to-side anastomosis of the artery prevents the occurrence of distal embolism in case of local thrombosis. Suppression of all aneurysmal fistulas is recommended whenever a kidney transplant ensures satisfactory function with sufficient follow-up.

Adult↗
PubMed1992

Autosomal dominant polycystic kidney disease with primary hyperaldosteronism.

We report three cases of primary aldosteronism associated with autosomal dominant polycystic kidney disease. The diagnosis of primary hyperaldosteronism was based on the presence of hypokalaemia with excessive urinary potassium excretion and/or the characteristic hormonal changes. Renal function impairment due to autosomal dominant polycystic kidney disease could mask hypokalaemia. The interpretation of adrenal imagery may be hindered by adjacent renal cysts. In one case an adrenal adenoma was detected and surgically removed, with only partial correction of the blood pressure. This could be explained by the persisting underlying autosomal dominant polycystic kidney disease. We conclude that in a hypertensive patient with polycystic kidney disease, extrarenal causes of hypertension may be present.

Adult↗
PubMed1992

[Aortoiliac surgery after renal transplantation. Authors' experience and review of the literature].

Eighteen patients who had undergone renal transplantation three months to 25 years earlier were operated on for treatment of complicated aortoiliac atherosclerosis: nine had aneurysms (of which one was leaking) and nine had stenotic or obstructive lesions. Except for the first patient, operated on in 1973, in whom the kidney was protected by general hypothermia, no special measure was used to protect the kidneys in the other 17 patients. A transient increase in creatininemia occurred in the majority of cases during postoperative period. All patients had regained renal function identical to the preoperative state in less than 10 days. Three patients had significant improvement of renal function which lasted in the long term follow-up. Such improvement was a result of correction of a lesion that was impairing renal blood flow. Results obtained in this series show that protection of the transplant during aortic surgery is not necessary, provided an adequate surgical technique is used. This technique is described: it avoids the complex methods employed in several previously reported cases and appears to be a safe procedure.

Adult↗
PubMed1991

Aortoiliac surgery in renal transplant patients.

Fifteen patients who had undergone renal transplantation 3 months to 25 years earlier were operated on for treatment of complicated aortoiliac atherosclerosis; eight had aneurysms and seven had stenotic or obstructive lesions. Except for the first patient, operated on in 1973, in whom the kidney was protected by general hypothermia, no special measure was used to protect the kidneys. A transient increase in creatinemia occurred in 11 patients during the postoperative period, whereas creatinine values remained unchanged in the other four. All patients had regained renal function identical to the + preoperative state in less than 10 days; three of them had significant improvement as a result of correction of a lesion that was impairing renal blood flow. Results obtained in this series show that protection of the transplant during aortic surgery is not necessary, provided an adequate surgical technique is used. This technique avoids the complex methods employed in the majority of previously reported cases and appears to be a safe procedure.

Adult↗
PubMed1991

[Surgical treatment of renal artery stenosis in children 60 surgically treated cases].

Sixty children with renal artery stenosis (unilateral in 44, bilateral in 16) underwent surgical treatment. Ten nephrectomies and 69 vascular repair procedures were performed. Postoperative follow-up ranged from one to 14 years. After surgery, blood pressure returned to normal and subsequently remained so in 54 patients without any antihypertensive medication. This represents a 90% cure rate. In six patients blood pressure remained high due to lesions of the renal parenchyma. Fibrous dysplasia of the renal artery was the prevailing pathologic finding. In children, associated lesions are especially frequent: coarctation of the abdominal aorta, stenosis, occlusion, aneurysms of the splanchnic arteries, pheochromocytoma. Postoperative prognosis of renovascular hypertension in children is good since atheroma and visceral or renal lesions are usually lacking.

Adolescent↗