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Biomedical subjects

E Goffin

Publications and source records attributed to E Goffin.

At least 37 records · Page 2Linked to original sources
PubMed1999

Regulation of aquaporin-1 and nitric oxide synthase isoforms in a rat model of acute peritonitis.

The loss of ultrafiltration (UF) that accompanies acute peritonitis is a common problem in peritoneal dialysis (PD). It has been suggested that changes in nitric oxide (NO)-mediated vascular tone and permeability might be involved in the loss of UF, whereas channel-mediated water permeability should not be affected. This study used a model of acute peritonitis in rats to characterize changes in PD parameters, in correlation with: (1) expression studies of water channel aquaporin-1 and NO synthase (NOS) isoforms and (2) enzymatic assays for NOS in the peritoneum. Compared with controls, rats with peritonitis had a higher removal of plasma urea, a faster glucose absorption, and a loss of UF. Additional changes, including high protein loss, elevated leukocyte counts in dialysate, positive bacterial cultures, edema, and mononuclear infiltrates, were similar to those observed in PD patients with acute peritonitis. Acute peritonitis in rats induced a major increase in total NOS activity, which was inversely correlated with free-water permeability. The increased NOS activity was mediated by both inducible (Ca2+-independent) and endothelial (Ca2+-dependent) NOS isoforms and was reflected by increased peritoneal staining for nitrotyrosine. In contrast, aquaporin-1 expression was unchanged in rats with peritonitis. These findings cast light on the pathophysiology of permeability changes and loss of UF that characterize acute peritonitis. In particular, these data suggest that a local production of NO, mediated by different NOS isoforms, might play a key role in these changes.

Acute Disease↗
PubMed1998

Combined heart-kidney transplantation: report on six cases.

BACKGROUND: Combined heart-kidney transplantation has become a new therapeutic solution for patients with coexisting, irreversible heart and kidney failure. Though this combined approach has several theoretical advantages over sequential transplantation, it has yet to be established that it does not jeopardize patient and graft outcomes. We here report our experience with six cases of combined heart-kidney transplantation from single donors and review the literature in order to clarify this issue. METHODS: Four patients were kidney-transplant candidates with severe heart failure and two were heart-transplant candidates with independent chronic renal failure. Donors were selected on the basis of weight and size matching, ABO compatibility, and negative T-cell cross-match. RESULTS: The heart was always grafted first. The surgical procedure was uneventful in all cases. Heart and kidney function recovered quickly in all patients. Two patients died, one at day 45 from heart subacute rejection and the other one at day 157 from cerebral haemorrhage. The four remaining patients are alive 23-84 months after transplantation (2-year survival rate: 67%) and have well-functioning kidneys (creatinine clearance 31-83 ml/min) and hearts (left ventricular ejection fraction 53-83%). Remarkably, four of six patients had no acute rejection episode of either organ. These patient and graft outcomes are in agreement with previous reports and compare favourably with the results of isolated heart and kidney transplantation. CONCLUSIONS: Combined heart-kidney transplantation from the same donor should be proposed to patients who would qualify for transplantation of each organ within a few years.

Adolescent↗
PubMed1998

Aquaporin-1 and endothelial nitric oxide synthase expression in capillary endothelia of human peritoneum.

Water transport during peritoneal dialysis (PD) requires ultrasmall pores in the capillary endothelium of the peritoneum and is impaired in the case of peritoneal inflammation. The water channel aquaporin (AQP)-1 has been proposed to be the ultrasmall pore in animal models. To substantiate the role of AQP-1 in the human peritoneum, we investigated the expression of AQP-1, AQP-2, and endothelial nitric oxide synthase (eNOS) in 19 peritoneal samples from normal subjects (n = 5), uremic patients treated by hemodialysis (n = 7) or PD (n = 4), and nonuremic patients (n = 3), using Western blotting and immunostaining. AQP-1 is very specifically located in capillary and venule endothelium but not in small-size arteries. In contrast, eNOS is located in all types of endothelia. Immunoblot for AQP-1 in human peritoneum reveals a 28-kDa band (unglycosylated AQP-1) and diffuse bands of 35-50 kDa (glycosylated AQP-1). Although AQP-1 expression is remarkably stable in all samples whatever their origin, eNOS (135 kDa) is upregulated in the three patients with ascites and/or peritonitis (1 PD and 2 nonuremic patients). AQP-2, regulated by vasopressin, is not expressed at the protein level in human peritoneum. This study 1) supports AQP-1 as the molecular counterpart of the ultrasmall pore in the human peritoneum and 2) demonstrates that AQP-1 and eNOS are regulated independently of each other in clinical conditions characterized by peritoneal inflammation.

Adolescent↗
PubMed1996

Hepatitis C infection in renal transplant patients: new insights and unanswered questions.

The prevalence of HCV infection in a population of renal transplantation patients is mostly dependent on that preexisting before transplantation. It also has been demonstrated that HCV infection can be transmitted by the renal graft. Although grafting an HCV+ kidney does not affect survival 5 years after surgery, the risk incurred by recipients on the longer term is unclear. A suggestion has been made to reserve HCV+ kidneys for recipients who are themselves HCV+. However, it has been established that a given HCV strain has little chance of inducing immunity to a different HCV strain. This is why the use of HCV+ kidneys no longer meets consensus. It could be considered to match the recipient and the graft with regard to the HCV strain when genotype identification is routinely available, quick and reliable. Immunosuppressive therapy enhances viral replication. Its long-term effect on the course of HCV disease is unclear. In particular, no studies have compared the long-term outcome of HCV+ patients treated by haemodialysis and transplantation. The data available on the 10-year outcome of HCV+ grafted patients are nonetheless reassuring. At least they allow considering renal transplantation to non-cirrhotic HCV+ patients. Several issues related to the interaction between HCV and immunosuppressive therapy remain to be clarified. Does the viral strain play a role in the course of infection under immunosuppressive treatment? Does immunosuppressive treatment promote strain mutagenesis? Does HCV infection require modulation of the immunosuppressive treatment?

Antibodies, Viral↗
PubMed1996

Outcome of renal replacement therapy in autosomal dominant polycystic kidney disease.

We review our own experience as well as pertinent literature on the outcome of renal replacement therapy (RRT) in autosomal dominant polycystic kidney disease (ADPKD). Due to the virtual absence of data on peritoneal dialysis in ADPKD, we deal only with haemodialysis (HD) and renal transplantation (TP). Special attention is paid to the renal and extrarenal complications of ADPKD. On HD, 5 year survival is 10-15% greater in ADPKD than in non-ADPKD patients, probably because of a lower cardiac mortality of ADPKD patients. After TP, patient as well as graft survival rates of ADPKD patients are similar to those of non-ADPKD patients. On HD, the prevalence of renal pain, gross haematuria and renal infection is significantly greater in ADPKD (36, 36 and 16% respectively) than in non-ADPKD patients (2, 16 and 2% respectively), but these complications are rarely severe. Other than preparation for TP, nephrectomy is required in only 4% of ADPKD patients on HD. With a policy of selective removal of problematic kidneys before TP, complications due to native polycystic kidneys do not frequently occur after TP, leading to post-TP nephrectomy in only 7% of ADPKD patients. There is a mild excess of stroke among ADPKD patients undergoing RRT, the contribution of intracranial aneurysm rupture not being clearly defined. Symptoms related to hepatic cysts are rare and to cardiac valvular abnormalities very rare. In conclusion, RRT is at least as successful in ADPKD as in non-ADPKD patients. Renal complications are frequent but rarely severe. Extrarenal complications are not frequent.

Humans↗
PubMed1995

Factors influencing serum levels and peritoneal clearances of low molecular weight proteins in continuous ambulatory peritoneal dialysis.

To identify the factors influencing the serum concentrations and the peritoneal clearances of low molecular weight proteins (LMWP), fourteen patients on continuous ambulatory peritoneal dialysis (CAPD) for 1 to 57 (mean 9.4) months were examined. LMWP [Beta 2-microglobulin (Beta 2m, molecular wt 11.8 kD), cystatin C (cyst C, molecular wt 13.2 kD), Clara cell protein (CC16, molecular wt 15.8 kD), retinol-binding protein (RBP, molecular wt 21 kD) and alpha 1-microglobulin (Alpha 1m, molecular wt 33 kD)] and high molecular weight proteins (HMWP) [albumin (Alb, molecular wt 66 kD), immunoglobulins (IgG, molecular wt 170 kD and IgM, molecular wt 600 kD) and alpha 2-macroglobulin (Alpha 2m, molecular wt 718 kD)] were determined by latex immunoassay in the serum and dialysate collected during the peritoneal equilibration test (PET) with 2.27% dextrose (N = 14), and in dialysate from 56 standard exchanges, performed the day preceding PET, with 1.36% (N = 21), 2.27% (N = 23) and 3.86% (N = 12) dextrose. Determinants of serum concentrations and transperitoneal clearances of the proteins were traced by stepwise regression analysis using as possible contributors age, sex, residual diuresis, duration of the therapy (for serum concentrations), molecular radius of the protein and peritoneal membrane characteristics (for peritoneal clearances). LMWP serum concentrations were markedly increased whereas serum concentrations of HMWP were within the normal range. Residual diuresis, age and duration of dialysis emerged as significant determinants of serum concentration of some proteins, whereas transperitoneal clearance was dependent mainly on the size of the protein and, only for HMWP, on the dwell time. Residual diuresis was inversely related to the serum concentrations of four LMWP. Age was negatively correlated to the serum concentrations of beta 2m, CC16 and RBP. RBP and Alb were the only proteins whose serum concentration significantly decreased with time on CAPD. The relationship between peritoneal clearance and M(r) shows two slopes suggesting the existence of two populations of pores in the peritoneal capillary wall: small pores of about 20 to 25 A radius and large pores exceeding 100 A radius. A long dialysis cycle is associated with significant loss of HMWP only. Daily peritoneal protein losses, in mg (mean +/- SD), were as follows: Beta 2m 43.4 +/- 4.5; cyst C 9.6 +/- 1.8; CC16 1.8 +/- 0.3; RBP 58.9 +/- 11.1; Alpha 1m 149.5 +/- 15.7; Alb 6570 +/- 530; IgG 750 +/- 111; IgM 46.4 +/- 14.9; and alpha 2m 67.0 +/- 12.7. In conclusion, LMWP concentrations in the serum of patients on CAPD were markedly increased and influenced mainly by patient-related factors (residual diuresis and age). Serum albumin and RBP declined with the duration of dialysis. Peritoneal protein loss was determined by the size of the protein and, for large proteins, by the dwell time. The peritoneum behaves as a membrane with at least two populations of pores.

Adult↗
PubMed1995

Implications of chronic hepatitis B or hepatitis C infection for renal transplant candidates.

Hepatic cirrhosis and clinically active hepatitis due to HBV or HCV infection clearly contra-indicate kidney transplantation. More controversial is the attitude to be adopted towards candidates with clinically quiescent chronic HBV or HCV infection. The presence of the HBs antigen does not adversely affect survival or increase morbidity on maintenance haemodialysis, at least during the first decade. After transplantation, by contrast, the long-term outcome of HBV infection is undoubtedly worse than on haemodialysis: more patients develop chronic hepatitis and eventually die from liver disease. The risk of fatal liver disease after transplantation is greater in patients with markers of active viral replication before transplant and in those with severe histological liver lesions. Pretransplant candidates should be warned of this significant risk factor. Comparison of survival of HCV-infected patients on haemodialysis and after transplantation is not yet possible. The outcome of HCV infection after transplantation appears less severe than that of HBV infection: the survival of anti-HCV-positive patients is similar to that of anti-HCV-negative patients, at least during the first decade after transplantation. Liver biochemical abnormalities, serological markers and detection of HCV RNA are of little value to identify patients at greater risk of poor outcome after transplantation. Only liver biopsy might help identify such patients. Both efficacy and risks of antiviral therapies are yet to be properly assessed during haemodialysis. Preliminary evidence suggests that interferon therapy given after transplantation entails an unacceptable rate of deterioration in graft function.(ABSTRACT TRUNCATED AT 250 WORDS)

Attitude of Health Personnel↗