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Biomedical subjects

R Dorent

Publications and source records attributed to R Dorent.

At least 37 records · Page 2Linked to original sources

Photopheresis for the prevention of rejection in cardiac transplantation. Photopheresis Transplantation Study Group.

BACKGROUND: Photopheresis is an immunoregulatory technique in which lymphocytes are reinfused after exposure to a photoactive compound (methoxsalen) and ultraviolet A light. We performed a preliminary study to assess the safety and efficacy of photopheresis in the prevention of acute rejection of cardiac allografts. METHODS: A total of 60 consecutive eligible recipients of primary cardiac transplants were randomly assigned to standard triple-drug immunosuppressive therapy (cyclosporine, azathioprine, and prednisone) alone or in conjunction with photopheresis. The photopheresis group received a total of 24 photopheresis treatments, each pair of treatments given on two consecutive days, during the first six months after transplantation. The regimen for maintenance immunosuppression, the definition and treatment of rejection episodes, the use of prophylactic antibiotics, and the schedule for cardiac biopsies were standardized among all 12 study centers. All the cardiac-biopsy samples were graded in a blinded manner at a central pathology laboratory. Plasma from the subgroup of 34 patients (57 percent) who were enrolled at the nine U.S. centers was analyzed by polymerase-chain-reaction amplification for cytomegalovirus DNA. RESULTS: After six months of follow-up, the mean (+/-SD) number of episodes of acute rejection per patient was 1.44+/-1.0 in the standard-therapy group, as compared with 0.91+/-1.0 in the photopheresis group (P=0.04). Significantly more patients in the photopheresis group had one rejection episode or none (27 of 33) than in the standard-therapy group (14 of 27), and significantly fewer patients in the photopheresis group had two or more rejection episodes (6 of 33) than in the standard-therapy group (13 of 27, P=0.02). There was no significant difference in the time to a first episode of rejection, the incidence of rejection associated with hemodynamic compromise, or survival at 6 and 12 months. Although there were no significant differences in the rates or types of infection, cytomegalovirus DNA was detected significantly less frequently in the photopheresis group than in the standard-therapy group (P=0.04). CONCLUSIONS: In this pilot study, the addition of photopheresis to triple-drug immunosuppressive therapy significantly decreased the risk of cardiac rejection without increasing the incidence of infection.

Combined Modality Therapy↗

Pacemaker infective endocarditis.

We identified 33 patients with definite pacemaker endocarditis--that is, with direct evidence of infective endocarditis, based on surgery or autopsy histologic findings of or bacteriologic findings (Gram stain or culture) of valvular vegetation or electrode-tip wire vegetation. Most of the patients (75%) were > or = 60 years of age (mean 66 +/- 3; range 21 to 86). Pouch hematoma or inflammation was common (58%), but other predisposing factors for endocarditis were rare. At the time that pacemaker endocarditis was found, the mean number of leads was 2.4 +/- 1.1 (range 1 to 7). The interval from the last procedure to diagnosis of endocarditis was 20 +/- 4 months (range 1 to 72). Endocarditis appeared after pacemaker implantation, early (< 3 months) in 10 patients and late (> or = 3 months) in 23 patients. Fever was the most common symptom, being isolated in 36%, associated with a poor general condition in 24%, and associated with septic shock in 9%. Transthoracic echocardiography showed vegetations in only 2 of 9 patients. Transesophageal echocardiography demonstrated the presence of lead vegetations (n = 20) or tricuspid vegetations (n = 3) in 23 of 24 patients (96%; p <0.0001 compared with transthoracic echocardiography). Pulmonary scintigraphy showed a typical pulmonary embolization in 7 of 17 patients (41%). Pathogens were mainly isolated from blood (82%) and lead (91%) cultures. The major pathogens causing pacemaker endocarditis were Staphylococcus epidermidis (n = 17) and S. aureus (n = 7). S. epidermidis was found more often in early than in late endocarditis (90% vs 50%; p = 0.05). All patients were treated with prolonged antibiotic regimens before and after electrode removal. Electrode removal was achieved by surgery (n = 29) or traction (n = 4). Associated procedures were performed in 9 patients. After the intensive care period, only 17 patients needed a new permanent pacemaker. Overall mortality was 24% after a mean follow-up period of 22 +/- 4 months (range 1 to 88). Eight patients who were significantly older (74 +/- 3 vs 63 +/- 3 years; p = 0.05) died < or = 2 months after electrode removal, whereas 25 were alive and asymptomatic.

Adult↗

Biliary surgery after heart transplantation.

BACKGROUND: Biliary tract diseases are frequent in heart transplant recipients, with significant morbidity and mortality. Since the first presentation of gallstones in this population is often acute cholecystitis, asymptomatic cholelithiasis should not be considered benign. PATIENTS AND METHODS: We retrospectively reviewed 18 heart transplant recipients who underwent cholecystectomy from January 1991 to June 1997. We intentionally chose to perform a straightforward open procedure when acute cholecystitis was suspected (3 patients). A laparoscopic cholecystectomy was performed in all the other cases (15 patients) without conversion to open procedure. CONCLUSION: Since no significant complications were observed in our patients, we believe that transplant recipients with cholelithiasis should undergo laparoscopic cholecystectomy in their posttransplantation course regardless of the symptomatic status of their biliary tract.

Adult↗

Heart retransplantation: a 23-year single-center clinical experience.

BACKGROUND: The main causes of allograft failure after cardiac transplantation are primary graft dysfunction, intractable acute rejection, and coronary graft disease. Despite the important progress in the last several years in graft preservation, surgical techniques, immunosuppression, and treatment of coronary graft disease, retransplantation in selected cases is the only way to achieve long-term recipient survival. METHODS: We compare here in a case-control study 24 retransplantations with 47 first transplants in patients matched for date of transplantation. RESULTS: Between 1973 and 1996, 1,063 patients underwent cardiac transplantation in our institution. In this cohort, 22 patients had a total of 24 retransplantations (2 second-time retransplantations). The causes of retransplantations were primary graft failure (n=4), acute rejection (n=7), coronary graft disease (n=11), and miscellaneous (n=2). Survival at 1 and 5 years of patients with retransplantations is 45.5% and 31.2%, and survival of control patients is 59.4% and 38.8% (p=0.07). An interval between first transplantation and retransplantation shorter (n=11) or longer (n=13) than 1 year is associated with a 1-year survival of 27.3% and 61.5% and a 4-year survival of 27.3% and 46%, respectively (not significant). Intervals shorter than 1 year between first transplantation and retransplantation were exclusively secondary to primary graft failure or intractable acute rejection. CONCLUSIONS: In the face of lack of donor grafts, these and other data indicate that retransplantation should be considered cautiously, especially when the interval between the first transplantation and retransplantation is short.

Acute Disease↗

Posttransplant lymphoproliferative disorders not associated with Epstein-Barr virus: a distinct entity?

PURPOSE: Organ recipients are at a high risk of posttransplant lymphoproliferative disorders (PTLD) as a result of immunosuppressive therapy. Most B-cell lymphomas are associated with Epstein-Barr virus (EBV) infection. We describe a morphologically and clinically distinct group of PTLD in 11 patients that occurred late after organ transplantation and were not associated with EBV. PATIENTS AND METHODS: There were seven kidney, three heart, and one liver transplant recipients (group I). The clinical manifestations, pathologic findings, treatment, and outcome were compared with those in 21 patients with EBV-associated PTLD treated in our institution (group II). EBV was detected with at least two techniques: Epstein-Barr-encoded RNA (EBER) in situ hybridization with EBER 1 + 2 probes, Southern blotting, and detection of latent membrane protein 1 (LMP1) expression by immunohistochemistry. RESULTS: The time between transplantation and the diagnosis of lymphoma ranged from 180 to 10,220 days in group I (mean, 2,234; median, 1,800) and from 60 to 2,100 days in group II (mean, 546; median, 180), and was significantly shorter in group II (P = .02). Among 19 tumors diagnosed within 2 years after the graft, 16 were associated with EBV; among 13 tumors diagnosed after more than 2 years, only five were associated with EBV. All of the B-cell PTLDs in group I were classified as monomorphic, meeting the criteria of B diffuse large-cell lymphoma (B-DLCL) with a component of immunoblasts, and genotyping confirmed their monoclonality. Three tumors were T-cell pleomorphic lymphomas. Tumor sites were mainly bone marrow and lymph nodes. Overall median survival was 1 month in group I and 37 months in group II, with two patients still alive in group I and nine in group II. The survival time was significantly longer in group II (P < .01). CONCLUSION: EBV-negative PTLD may be a late serious complication of organ transplantation. Half the tumors observed after kidney transplantation in our center were not associated with EBV and emerged after more than 5 years, which suggests the number of EBV-negative PTLDs in organ recipients might increase with time.

Adolescent↗

La Pitié heart transplantation: 30-year single center clinical experience.

At La Pitié Hospital, 1,184 patients underwent cardiac transplantation for end-stage cardiac disease (1,122 orthotopic and 62 heterotopic) between April 1968-November 1998. Since April 1986, 140 patients have been supported using several different mechanical assist devices as a bridge to transplantation. Twenty-four retransplantations (2.2%) were performed for primary graft failure in 4 (17%), refractory acute rejection in 7(29%), coronary graft disease in 11 (46%) and others in 2 (8%) patients. In a case-control study, retransplanted patients were matched with first transplant patients and survival rates at one and 5 years were 59.4% and 38.8% compared with survival rates for retransplanted patients of 45.4% and 31.2%, respectively. Seventy-four patients survived more than 10 years (61 males, 13 females). Mortality did not increase after 10 years. Unfortunately many suffered complications: 77% had hypertension, hypercholesterolemia (22%), hyperuricemia (41%), osteoporosis (11%), osteonecrosis (5%) and diabetes (7%). Renal function remains one of the main problems; 16% had a creatinine > 180 mumol/L and patients are on chronic dialysis.

Actuarial Analysis↗

European Multicenter Tacrolimus (FK506) Heart Pilot Study: one-year results--European Tacrolimus Multicenter Heart Study Group.

BACKGROUND: Tacrolimus (FK506) may represent a major advance in the management of allograft rejection after solid organ transplantation. In August 1994 a European heart transplantation pilot study was initiated to assess the efficacy and safety of tacrolimus when administered exclusively through an oral route. METHODS: Eighty-two heart transplant recipients were randomized to treatment (2:1 ratio) with either tacrolimus- (n=54) or cyclosporine-based therapy (n=28). RESULTS: No significant differences were evident between the two treatment groups in either rejection or survival rates at 1 year. Kaplan-Meier estimates of the freedom from rejection were 26.3% and 18.5%, respectively, for the tacrolimus and cyclosporine treatment groups (p=.444). Survival rates were 79.6% and 92.9% (p=.125). At 3 of the 5 centers, patients received antithymocyte globulin during the immediate postoperative period and fared better than those who did not (with acute rejection-free rates of 49.2% and 26.7% for tacrolimus and cyclosporine, respectively [p=.080], as opposed to 7.1% and 8.3% [p=.965]; patient survival rates of 84.6% and 93.3% [p=.382] vs 75.0% and 92.3% [p=.243]). The overall rates of infection, impaired renal function (31.5% vs 21.4%), and glucose intolerance (7.0% vs 4.3%) did not differ significantly between the tacrolimus and cyclosporine treatment groups. Tacrolimus seemed to possess an advantage with regard to a reduced requirement for antihypertensive therapy (59.5% vs 87.5%, p=.025). CONCLUSIONS: Immunosuppression with oral tacrolimus provides a viable alternative to treatment with cyclosporine, particularly when administered in conjunction with antibody therapy. Further studies are warranted to optimize the administration of tacrolimus in this indication.

Administration, Oral↗

[Alcoholic cardiomyopathy and heart transplantation].

The recognition of alcoholic cardiomyopathy in patients with dilated cardiomyopathy is essential as they may regress, at least partially in a relatively short period, with abstention. The clinical history is the key to diagnosis because no other specific feature can identify the cause. Between January 1984 and July 1995, 26 candidates for cardiac transplantation with dilated cardiomyopathy and chronic alcoholism improved after withdrawal of alcohol. None of these patients was placed on the surgical waiting list. Patients with ischaemic cardiomyopathy, valvular disease or previous surgery for valvular hypertensive or congenital heart disease, documented viral myocarditis or connective tissue diseases, were excluded. The diagnostic criterion of chronic alcoholism was a total alcohol consumption of 292 kg and a duration of alcohol abuse of over 10 years. In addition to the clinical features, biological, electrocardiographic, echocardiographic and haemodynamic parameters were analysed. The mean age of the patients was 48 +/- 8 years. There were 25 men and 1 woman. The total mean alcohol consumption was 1,492 kg. The average follow-up period was 63 +/- 41 months. The interval between the onset of symptoms and abstention was 25 months. Haemodynamic improvement was observed in 25 cases. The average interval between alcoholic abstention and recovery was 11.7 months. One patient died suddenly. Improvement of symptoms, decrease of the cardiothoracic ratio and improvement of echocardiographic parameters were statistically significant. The increase in angiographic or isotopic ejection fraction and cardiac index and the decrease in mean pulmonary artery pressures were also statistically significant. These results confirmed the diagnosis of alcoholic cardiomyopathy. Therefore, patients with chronic alcohol abuse and dilated cardiomyopathy must be identified and treated for this problem and not placed on the waiting list for cardiac transplantation unless no improvement is observed after about 3 months of abstention.

Adult↗

Endothelin-1 in the lungs of patients with pulmonary hypertension.

BACKGROUND: Pulmonary hypertension (PH) is characterized by an increase in vascular tone and an abnormal proliferation of muscle cells in the walls of pulmonary arteries. Recent studies have found high plasma endothelin-1 (ET-1) concentrations in patients with PH. This study was conducted to assess whether elevated circulating ET-1 levels in PH really reflect excessive local pulmonary production. METHODS: We prospectively studied ET-1 concentration in lung specimens from 6 control subjects and 13 patients with severe PH referred for lung or heart-lung transplantation (6 patients had primary PH and 7 PH secondary to congenital heart defect). Endothelin-like immunoreactivity (ET-LI) was measured in plasma and lung tissue, using a radioimmunoassay, after ET-1 extraction. Reverse-phase high-performance liquid chromatography was also performed. RESULTS: Peripheral venous plasma ET-LI concentrations in patients with PH, whatever the cause, were greater than those in controls (10.7 +/- 0.8 vs 5.3 +/- 0.7 pg/ml; P < 0.0005). Pulmonary ET-LI was significantly higher in patients with PH, irrespective of its cause, than in controls (25.2 +/- 5.1 vs 8.1 +/- 1.1 pg/mg, P < 0.03). ET-LI pulmonary concentrations were slightly higher in Eisenmenger than in primary PH, but this was not significant (27.1 +/- 8.6 vs 22.8 +/- 5.4 pg/mg). Linear regression analysis indicated a small but significant correlation between ET-LI pulmonary concentrations and pulmonary vascular resistance in the patients with PH (r = 0.38; P = 0.047). In each case, HPLC separation of ET indicated that most of the immuno-reactivity was detected in the same fraction as ET-1. CONCLUSIONS: The striking increase in ET-1 pulmonary concentration provides new evidence that excessive local pulmonary ET-1 production may contribute to the vascular abnormalities of pulmonary hypertension.

Adult↗

Position-related factors in mitral and tricuspid bioprostheses degenerative changes.

We report clinicopathological findings in 15 patients in whom the same bioprosthesis (BP) had been implanted simultaneously in both mitral and tricuspid positions. The aim of the study was to investigate whether position-related factors played an important role in BP degeneration. There were 14 women and 1 man with a mean age of 34 +/- 11 years. The indications for the initial operation were rheumatic in 14 cases and endocarditis in one patient. The mean interval before reoperation was 7.5 +/- 3.3 years. Predominant cause of reoperation was: structural deterioration of both mitral and tricuspid BPs (6), mitral regurgitation (5), tricuspid BP dysfunction (1), para-aortic leak (1), mitro-aortic thrombi (1). Calcific deposits were the principal cause of early deterioration of mitral BPs and the major cause of late tricuspid BPs dysfunction. This lesion was predominantly related to local factors. Cuspal tears were the principal cause of late (> 9 yrs) mitral BP failure and most probably related to mechanical stress. Extensive fibrosis affected only tricuspid bioprostheses. In 7 patients more extensive degenerative changes occurred in bioprostheses in the mitral rather than the tricuspid position (Group I). However, in the remaining eight the magnitude of the changes was very similar in the two positions (Group II). The interval before reoperation was significantly longer in patients of Group II (9.8 yrs, range 5-13) than patients in Group I (4.9 yrs, range 3-6), (p < 0.01). We concluded that position-related factors exert a major role in bioprosthetic failure. These factors are more deleterious in the mitral position than in the tricuspid position.

Adolescent↗

Heart transplant for the failing ischaemic ventricle.

Clinical application of heart transplantation goes beyond 28 years experience. Ischaemic heart diseases remain, with idiopathic cardiomyopathies, the main indications for cardiac transplant. A combination of haemodynamic, contractile and viability measurements may be useful to choose between transplant and coronary revascularization for the failing ischaemic ventricle. Advances in the detection of early rejection, improved organ preservation procedures, and the introduction of new immunosuppressive therapy protocols have produced dramatic results in heart transplantation. Late graft atherosclerosis remains a serious threat despite retransplantation and, in some cases, mechanical circulatory support.

Contraindications↗

Plasma levels of thrombomodulin in pulmonary hypertension.

BACKGROUND: Long-standing pulmonary hypertension (PH) leads to structural alterations of the pulmonary vasculature and its endothelium, and occlusion of small vessels by microthrombi. In patients with PH, the search for factors inducing or worsening endothelium damage and in situ thrombi is still ongoing. Thrombomodulin (TM), an endothelial cell membrane protein, is a receptor for thrombin and a major anticoagulant proteoglycan. PURPOSE: To analyze plasma TM levels in patients with different forms of severe PH. PATIENTS: We prospectively studied 32 consecutive patients with PH referred for heart, lung, or heart-lung transplantation: 11 patients with primary PH (group 1), 11 patients with secondary precapillary PH (Eisenmenger's syndrome, group 2) and 10 patients with secondary postcapillary PH due to congestive heart failure (group 3). Thirty-eight healthy subjects were also studied as a control group. METHODS: Plasma concentrations of TM were measured by an immunoenzymatic technique that uses two anti-TM monoclonal antibodies that have a strong avidity and react with different epitopes of the molecule. RESULTS: Thrombomodulin plasma levels decreased in all patients with precapillary PH, and this decrease was highly significant compared with controls (26 +/- 2 versus 44 +/- 2 ng/mL, P = 0.0001). In primary PH, the TM decrease was only significant in males whereas in the Eisenmenger's syndrome TM values were the lowest of all the patients studied, with mean values twice as low as controls (22 +/- 2 versus 44 +/- 2 ng/mL, P = 0.0001). In contrast, in postcapillary PH, studied only in males, TM levels were increased (85 +/- 17 versus 54 +/- 3 ng/mL, P = 0.02). Patients with precapillary PH had more severe disease than patients with postcapillary PH, with higher pulmonary artery pressure and pulmonary vascular resistance (P < 0.001). There was no correlation between TM plasma levels and all hemodynamic variables. CONCLUSION: We found low levels of plasma TM in patients with precapillary PH but not in postcapillary PH compared with healthy controls. This may be related to the severity of PH and may contribute to the initiation or worsening of in situ thromboses frequently found in pulmonary hypertension. Further studies should analyze whether other markers of endothelial cell damage are correlated with plasma TM levels in patients with precapillary pulmonary hypertension.

Adolescent↗

Cyclosporin A-mediated cholestasis in patients with chronic hepatitis after heart transplantation.

Viral chronic hepatitis often occurs in heart transplant recipients receiving cyclosporin. This essential immunosuppressive drug may induce cholestasis. We investigated the effect of treatment with cyclosporin on serum conjugated bile acids in patients with chronic hepatitis developing after heart transplantation. Fifty-nine patients were studied: 17 with chronic hepatitis, 15 heart transplant patients with normal alanine aminotransferase activity, and 27 heart transplant patients with chronic hepatitis, the last two groups receiving cyclosporin. Hepatic biochemical tests and total bile acid concentration were determined on fasting blood samples. The individual glyco- and tauroconjugated bile acids were quantified by high-performance liquid chromatography and direct spectrometry. In patients taking cyclosporin the bilirubin concentration and the alkaline phosphatase activity were increased only when hepatitis was present, in association with a slight increase in cholic acid level (5.13 microM vs. 0.68 microM; P < 0.01). Conjugated lithocholate concentration was dramatically higher when hepatitis and immunosuppression with cyclosporin were associated (1.17 microM vs. 0.03 and 0.04 microM; P < 0.01). Chenodeoxycholate was the main circulating bile acid only in the heart transplant patients treated with cyclosporin but without hepatitis. These results suggest that the mechanisms which explain the cyclosporin-associated modifications of the bile acid pool are different according to the presence or absence of hepatitis. The occurrence of hepatitis in patients on cyclosporin led to an increase in serum lithocholate and primary bile acid concentrations. Further studies are required to assess the effect of ursodeoxycholic acid for this cholestasis.

Adult↗

[Video-surgery for pericardial effusion. Technique and results].

Videosurgery is a relatively non-invasive method of draining the pericardium by the creation of a pleuropericardial window. It provides an excellent view of the thoracic cavity and allows selection of pericardial and pleural, pulmonary or mediastinal biopsy sites. The authors report their preliminary results with this technique. Between May 1994 and May 1995, 22 patients with pericardial effusions were operated by videosurgery at the Pitié Hospital. None of the patients had clinical signs of tamponade. The technique consists in introducing, through 2 or 3 thoracic incisions of 15 mm, trocarts allowing passage of an endoscopic camera and different surgical instruments. Access to the thoracic cavity enabled assessment of the pleura, evacuation of pleural effusions (n = 8) and biopsy of pleural nodules (n = 2). One pulmonary biopsy was performed. Opening the pericardium enabled evacuation of pericardial effusions averaging 622 ml. Pericardial biopsies showed appearances suggesting tuberculosis (n = 2), lupic vasculitis (n = 1) and post-radiation pericarditis (n = 1). In other cases, a histologic diagnosis of non-specific pericarditis was made. A biopsy of a pleural nodule showed undifferentiated carcinoma in one case. A pulmonary biopsy revealed the presence of relatively undifferentiated carcinoma. There were no complications related to the technique. There was one recurrence of pericardial effusion at one month in a patient with carcinoma of the lung who had previously had subxiphoid drainage. There were no cases of secondary pericardial constriction. Therefore, videosurgery is a relatively non-invasive and effective technique of pericardial drainage and biopsy. When there is no emergency, it is probably the method of choice in the treatment and diagnosis of pericardial effusions.

Adult↗