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Biomedical subjects

D Farge

Publications and source records attributed to D Farge.

At least 19 recordsLinked to original sources

Interactions between hemodynamic and hormonal modifications during PEEP-induced antidiuresis and antinatriuresis.

The interactions between hemodynamic and hormonal modifications during antidiuresis and antinatriuresis induced by positive end-expiratory pressure (PEEP) were studied in six patients under 15 cm H2O PEEP before PEEP and after the addition of lower body positive pressure (LBPP) to PEEP (PEEP+LBPP). We measured or calculated the following: cardiac index, systemic arterial, right atrial, pulmonary arterial, and pulmonary artery occlusive pressures; indexed renal blood flow (iodohippurate 131 sodium clearance); total blood volume (chromium 51 radiolabeled RBCs); glomerular filtration rate; urinary output; fractional excretion of sodium (FE Na+); plasma concentrations of antidiuretic hormone (ADH), plasma renin activity (PRA), norepinephrine and epinephrine; urinary concentration of PGE2 (PGE2u). Although LBPP application corrected PEEP deleterious effects on systemic and renal hemodynamics, sustained fall in Vu and in FE Na+ were observed. Antidiuresis was not due to ADH release. Sympathetic activation and high PRA appeared the main determinants of renal function alterations in PEEP ventilation.

Adult

[Thromboembolic disease and cancer].

Many anomalies in primary haemostasis, coagulation and fibrinolysis have been described which favour thrombosis in cancer patients. Cancer is often associated with other risk factors for thromboembolism which explain much of the increased frequency of thrombosis in these patients. Thromboembolism may precede cancer and sometimes is the inaugural manifestation leading to the diagnosis of cancer. Cancer occurs more frequently in patients with idiopathic recurrent venous thrombosis than in those with thrombosis due to other risk factors for thromboembolism. The results of antivitamin K therapy are disappointing: in retrospective series, recurrent thromboembolism occurred in 9% of the treated patients and severe haemorrhage in 27%. New therapies should be assessed in cancer patients with thromboembolism.

Anticoagulants

[Treatment of arterial hypertension in patients with organ transplantation].

The onset of predominantly systolic hypertension (HT) is the most common complication following organ transplantation. The hypertension is directly linked to the immunosuppressant treatment, particularly to the nephrotoxic and intrarenal and peripheral vasoconstrictor effects of cyclosporin. Treatment is based on the primary use of arteriolar vasodilators, but must be appropriate for the organ transplanted and the degree of HT. It is often necessary to administer two or three antihypertensive drugs, which must take into account the precautions for their use and possible interactions with cyclosporin: calcium channel inhibitors inhibit the vasoconstriction induced by cyclosporin, converting enzyme inhibitors slow the compensatory glomerular hyperfiltration, diuretics are effective versus this type of HT, which is sensitive to sodium depletion, and beta-blockers are useful in hypertensive patients who have undergone kidney or liver transplants, but less commonly used in cardiac transplant patients. Centrally-acting antihypertensives are used as a second option.

Antihypertensive Agents

[Treatment of venous thromboembolic disease in patients with cancer].

Results of classical anticoagulant therapy in cancer patients with venous thromboembolism (VT) are highly discussed. We retrospectively analysed the outcome of 43 patients with VT and cancer: 32% developed specific complications during either i.v. heparin therapy (10 +/- 0.9 days) or treatment by antivitamin K (106 +/- 14.9 days). Recurrence of thromboembolism (16%) and/or hemorrhages (16%) were much more frequent than in patients without cancer, underlying need for alternative therapy in cancer patients with VT.

Female

[Use of a synthetic prostacyclin in extracorporeal circulation].

Using a prostacyclin in conjunction with standard heparin might limit the occurrence of post-extracorporeal circulation (ECC) thrombopathy and reduce the risk of haemorrhage inherent in this technique. For this reason, we studied the effect of the prostacyclin analogue Iloprost (ZK 36 374), a drug which is active in man when given orally with a biological half-life of 30 min, and devised a double-blind randomized trial to evaluate the potential benefit of Iloprost versus placebo in 2 groups of 15 patients (A: placebo, B: Iloprost). An infusion of the drug in incremental doses (up to 12 ng kg-1 min-1) was begun before starting the ECC and was stopped at the end of the cardiopulmonary bypass, at the time of protamine injection. Significant arterial hypotension was observed during ECC in two patients of the Iloprost group. Comparison between Iloprost and placebo groups showed that the mean number of platelets was not significantly higher in the Iloprost group 20 min after the ECC and during the early post-operative recovery period. Platelet aggregability was higher after surgery in the Iloprost group than in the placebo group. There was no significant difference in post-bypass bleeding between the two groups. Thus, Iloprost does not reduce the fall in circulating platelets observed during cardiopulmonary bypass, but it might help in preserving the platelet function. However, the potential usefulness of the drug is limited by adverse haemodynamic reactions.

Adult

Primary gastrointestinal malignant lymphomas associated with Epstein-Barr virus after heart transplantation.

Gastrointestinal involvement has been reported in 12-21% of post-transplant lymphoproliferative disorders but is unusual in the setting of heart transplantation. We report four post-transplant lymphoproliferative disorders observed among the 174 heart transplant recipients of our series, all of which were primary malignant lymphomas of and confined to the digestive tract. The mean onset time from transplantation was 22 months. Small intestine lesions were present in all four patients, with gastric involvement in one. Histologically, the tumour was monomorphic of immunoblastic type in one case and polymorphic in the three other cases. Analysis of cytoplasmic immunoglobulins demonstrated the presence of a major monoclonal subset in all patients. Epstein-Barr virus genome was found in numerous tumour cells by in situ hybridization. The exclusive localization to the digestive tract and the lymphoepithelial lesions observed in two cases suggest that these lymphoproliferations might originate from mucosa-associated lymphoid tissue.

Adult

[Beneficial effects of perfusion of atrial natriuretic factor in acute post-ischemic renal insufficiency in the rat].

Owing to its capacity of increasing glomerular filtration, potential beneficial effects of atrial natriuretic factor (ANF) were assessed during a post ischemic acute renal insufficiency in rats. Renal insufficiency was obtained by clamping the renal artery during 30 min., and by performing a reperfusion during 2 hours in uninephrectomized rats. Three groups were defined: a control group where animals were submitted to an operation procedure without renal artery clamping, a control group were animals received a physiological serum perfusion (1.5 ml/h) during the renal reperfusion time and an experimental group where animals were administrated a rat 1-28 ANF perfusion (5 microns/ml in NaCl 0.9%, 1.5 ml/hour) during the reperfusion time. Insulin clearance (1.0 + 0.05 ml/h vs 0.7 + 0.05 ml/h, p < 0.01), and diuresis (32.9 +/- 3.6 microliters/min. vs 7.5 +/- 0.23 microliters/min., p < 0.01) were significantly higher in rats which were administrated a NaCl 0.9% perfusion. Histologically, a significant decrease in kidney weight and in he percentage of diseases nephrons was observed after reperfusion in ANF treated rats. The results obtained demonstrate that ANF perfusion in case of post ischemic acute renal insufficiency in rats improves the recovery of renal function and reduces the renal histologic lesions.

Acute Kidney Injury

[What position to take for Kaposi's sarcoma in organ transplantation?].

Kaposi's Sarcoma (KS) is a tumor of multicentric origin, accounting for 4% of the observed neoplasia among organ transplant recipients. Its exact pathogenesis is still unknown. The diagnosis must be suspected in view of skin and/or subcutaneous tumor lesions with potential visceral involvement, which are easily confirmed by histological examination. Initial staging of the disease in 4 subgroups allows to guide therapy and prognosis. Therapeutic options depend on the transplanted organ and on results of early staging at time of diagnosis and treatment may associate: decrease and/or cessation of immunosuppression, laser therapy, radiotherapy and/or chemotherapy.

Humans

[Kaposi's syndrome following transplantation].

Kaposi's sarcoma has particularly been described after renal transplantation. More recently, a number of cases have been reported after hepatic or cardiac transplantation. The fostering factors are the same as for the other Kaposi's sarcomas, while the HIV1 or HIV2 serology is always negative. Renal transplantation may increase the natural risk of Kaposi's sarcoma by a factor of 4 to 500. The immunodepressive treatment must be reduced in case of purely cutaneous Kaposi and interrupted in case of visceral involvement. Death generally occurs as a consequence of infections. Kaposi's sarcoma after heart transplantation has a poorer prognosis, with fatal evolution in the four cases observed out of the 967 cardiac transplantations performed in the Ile-de-France region from 1968 to 1990; the cause of death most often is graft rejection or an infection.

Heart Transplantation

Serum lipid abnormalities in heart transplant recipients: predominance of HDL2-like particles in the HDL pattern.

Accelerated coronary atherosclerosis is a major risk limiting long-term survival after heart transplantation and is commonly associated with dyslipoproteinemia even in subjects who were not dyslipoproteinemic before intervention. The purpose of this study was to analyse the abnormalities in the lipid profiles of 2 different groups of heart-transplanted males: 18 subjects with underlying ischemic heart disease (IHD) and 19 subjects with non-obstructive cardiomyopathy of unknown aetiology (CM). Both groups were compared to 33 healthy males. All patients were under immunosuppressive therapy including prednisone, cyclosporin A and azathioprine. A moderate hyperlipidemia was found in all transplant recipients, associated with high HDL-cholesterol concentrations in the CM group (1.80 +/- 0.37 vs. 1.29 +/- 0.23 mmol/l) and normal HDL-cholesterol levels in the IHD group (1.40 +/- 0.23 mmol/l). HDL subfractionation showed a marked increase in HDL2-cholesterol (CM: 1.12 +/- 0.32; IHD: 0.69 +/- 0.28; control: 0.40 +/- 0.17 mmol/l) while HDL3-cholesterol was significantly lower than in the control group. Analysis of HDL particle sizes showed in all transplant subjects an increase of an intermediate size particle HDL2a (diameter 9.0 +/- 0.10 nm) which is a minor form in control subjects. In the CM group, both the common HDL2b (10.2 +/- 0.13 nm) and HDL2a were abundant in 13 of 17 patients. The pattern was more heterogeneous in the IHD group but witnessed to a high frequency of HDL2a particles either alone (5/14) or associated with larger HDL2b (4/14) or with small HDL3 (4/14).(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiomyopathies

Effect of systemic hypertension on renal function and left ventricular hypertrophy in heart transplant recipients.

To evaluate the incidence, risk factors and effects of systemic hypertension on renal function and left ventricular hypertrophy after cardiac transplantation, 85 transplant recipients on triple drug, low dosage, immunosuppressive therapy were studied. After a mean follow-up period of 12.5 +/- 8.7 months, a high incidence of hypertension was observed in 57 (67%) of the patients, and 42 (71%) of the 57 had developed new hypertension. None of the pretransplant and posttransplant cardiovascular risk factors were significantly associated with posttransplant hypertension. Faster deterioration of renal function, as assessed by intraindividual variations of serum creatinine values, was demonstrated in hypertensive patients and appeared as an early indicator of cyclosporine nephrotoxicity in patients at risk for hypertension. Serial echocardiographic evaluations demonstrated an early increase in left ventricular mass and fractional shortening in both hypertensive and normotensive heart transplant recipients. Fractional shortening further diminished significantly in normotensive patients but remained elevated in hypertensive patients, demonstrating sustained enhanced contractility in this group. Further studies will help to determine the exact relation between cyclosporine dosages and hypertension and their respective roles in the development of renal insufficiency and left ventricular hypertrophy after cardiac transplantation.

Adult