Biomedical subjects

Willem Weimar

Publications and source records attributed to Willem Weimar.

77 records · Page 5Linked to original sources

PubMed2002

Impact of intraoperative donor management on short-term renal function after laparoscopic donor nephrectomy.

OBJECTIVE: To determine whether intraoperative diuresis, postoperative recovery, and early graft function differ between laparoscopic open nephrectomy (LDN) and open donor nephrectomy (ODN). SUMMARY BACKGROUND DATA: Laparoscopic donor nephrectomy can reduce donor complications in terms of decreased pain and shorter convalescence. Although its technical feasibility has been established, concerns have been raised about the impaired renal function resulting from pneumoperitoneum and short- and long-term function of kidneys removed by LDN. METHODS: Between December 1997 and December 2000, 89 LDNs were performed at the authors' institution. These were compared with 83 conventional ODNs performed between January 1994 and December 1997. Graft function, intraoperative variables, and clinical outcome were compared. RESULTS: Laparoscopic donor nephrectomy was attempted in 89 patients and completed in 91% (81/89). Length of hospital stay was significantly shorter in the laparoscopic group. During kidney dissection, the amount of fluids administered and intraoperative diuresis were significantly lower for LDN. In recipients, mean serum creatinine was higher after LDN compared with ODN 1 day after surgery. From postoperative days 2 until 28, there were no differences in serum creatinine. Graft survival rates were similar for LDN and ODN. CONCLUSIONS: Donors can benefit from an improvement in postoperative recovery after LDN. Assessment of an adequate perioperative hydration protocol is mandatory to ensure optimal kidney quality during laparoscopic procurement. The initial graft survival and function rates justify continued development and adoption of LDN.

Adult↗

PubMed2002

Withdrawal of cyclosporine or prednisone six months after kidney transplantation in patients on triple drug therapy: a randomized, prospective, multicenter study.

Uncertainty exists regarding the necessity of continuing triple therapy consisting of mycophenolate mofetil (MMF), cyclosporine (CsA), and prednisone (Pred) after kidney transplantation (RTx). At 6 mo after RTx, 212 patients were randomized to stop CsA (n = 63), stop Pred (n = 76), or continue triple drug therapy (n = 73). The MMF dose was 1000 mg twice daily, target CsA trough levels were 150 ng/ml, and Pred dose was 0.10 mg/kg per d. Follow-up was until 24 mo after RTx. Biopsy-proven acute rejection occurred in 14 (22%) of 63 patients after CsA withdrawal compared with 3 (4%) of 76 in the Pred withdrawal group (P = 0.001) and 1 (1.4%) of 73 in the control group (P = 0.0001). Biopsy-proven chronic rejection was present in one patient in the control group, in nine patients after CsA withdrawal (P = 0.006 versus control group); and in four patients after discontinuation of Pred (NS). Graft loss occurred in two versus one patient after CsA or Pred withdrawal, respectively, and in two patients in the control group (NS). Patients who successfully withdrew CsA had a significantly lower serum creatinine during follow-up. Pred withdrawal resulted in a reduction in mean arterial pressure, and the total cholesterol/HDL ratio increased. In conclusion, rapid CsA withdrawal at 6 mo after RTx results in a significantly increased incidence of biopsy-proven acute and chronic rejection. Pred withdrawal was safe and resulted in a reduction in mean arterial pressure. However, patient and graft survival and renal function 2 yr after RTx were not different among groups.

Adult↗

PubMed2002

The presence of immune stimulatory cells in fresh and cryopreserved donor aortic and pulmonary valve allografts.

BACKGROUND AND AIM OF THE STUDY: Heart valve allografts (HVA) used for valve replacement or ventricular outflow tract reconstruction may suffer from structural deterioration due to donor-specific immune responses. The presence of immune stimulatory cells, including dendritic cells and activated endothelial cells, has not been studied thoroughly in aortic or pulmonary HVA. The presence and distribution of these cells in both aortic and pulmonary HVA, before and after cryopreservation, was analyzed immunohistochemically. METHODS: Aortic (n = 16) and pulmonary (n = 13) HVA, discarded for implantation due to morphological or technical reasons, were obtained from 12 heart-beating and nine non-heart-beating tissue donors. Aortic and pulmonary HVA were dissected longitudinally into two symmetric sections by splicing of the non-coronary aortic and non-facing pulmonary cusps. Each symmetric half contained one-and-a-half valve cusps attached to the vascular wall. Fresh halves were directly fixed in formaldehyde, and analyzed immunohistochemically. The corresponding halves of the valves were decontaminated, cryopreserved, stored for at least three weeks and thereafter thawed according to the Heart Valve Bank protocol before analysis. RESULTS: Activated endothelial cells, expressing PECAM-1 (CD31), VCAM-1 and HLA class II molecules covered at least 50% of fresh valvular surfaces. A comprehensive vascular network was found in the myocardial rim and adventitial layer, which was covered entirely by activated endothelial cells. HLA class II-positive macrophages (CD68) and T lymphocytes (CD3) were found scattered in the stroma and subendothelial layer of the valve leaflets. Mononuclear cell clusters were found predominantly in relation to native degenerative foci, and more often in aortic valves. No difference in cellular distribution was observed between the two donor types. Dendritic cells positive for both S100 and CD45 were not found in immuno-double-stained sections. Cryopreservation resulted in minor structural alterations in the vascular wall, and an increase of cells with pycnotic nuclei and reduction of adhesion molecule expression on endothelial cells. All fresh and cryopreserved aortic and pulmonary HVA contained abundant HLA class II-positive endothelial cells and sparse distribution of mononuclear cells in the luminal and adventitial layers. CONCLUSION: Cryopreservation minimally affected the extracellular matrix of HVA and diminished the cellularity of the valve graft, while the HLA class II expression of cells was not abrogated. Aortic valve allografts harbor more mononuclear cells than their pulmonary counterparts. The absence of dendritic cells (professional antigen-presenting cells) is compensated by the preservation of other cells expressing HLA class II molecules predominantly in the endothelium; this may be responsible for the initiation of a specific immune response against HVA.

Adult↗

PubMed2002

Frequencies of donor-reactive helper T lymphocytes correlate with rejection of aortic valve allografts in rats.

BACKGROUND AND AIMS OF THE STUDY: Human valve allografts are commonly used in cardiac surgery for congenital and acquired valve diseases. Particularly in the pediatric population, these allografts are prone to fail in the long term, and require replacement. In part, this failure may be due to immunological phenomena. The frequency of helper T lymphocytes (HTLf) measured in peripheral blood and spleen serves as a parameter for acute rejection in organ transplantation. The value of this parameter in valve transplantation was studied using the 'Rotterdam' implantation model in rats. METHODS: HTLf were determined in peripheral blood and spleen at seven and 21 days after allogeneic (WAG-->DA) and syngeneic (DA-->DA) implantation of an aortic valved conduit. Valve competence was tested pre-implantation, at days 7 and 21 after implantation, and after explantation using a retrograde saline injection. Explanted valves were examined histologically. RESULTS: At seven days after allogeneic valve transplantation, HTLf in spleen (median 71/10(6)), but not in peripheral blood (median 26/106) were significantly elevated. At 21 days after allogeneic transplantation, a significant increase in HTLf was seen in both peripheral blood (median 10(9)/10(6)) and spleen (median 92/10(6)). All five (100%) syngeneic grafts and five of seven (71%) allografts were competent at day 7. At day 21, all five syngeneic grafts (100%) and zero allografts (0%) remained competent (p = 0.01). Histologically, mononuclear cell infiltration into the allogeneic valve leaflets and in the vascular wall was observed at day 7. At day 21, valve leaflets appeared to be acellular and deformed. All syngeneic valve grafts retained normal morphology. CONCLUSION: After aortic valve allografting in the rat, HTLf correlate with valve dysfunction and histopathological signs of rejection. Therefore, HTLf-analysis may be a useful tool in monitoring the cellular immune response as an indicator for early graft dysfunction due to rejection in clinical valve transplantation.

Animals↗

PubMed2001

A controlled trial comparing two doses of cyclosporine in conjunction with mycophenolate mofetil and corticosteroids.

It is unknown whether the addition of mycophenolate mofetil (MMF) to cyclosporine (CsA) and prednisone after renal transplantation (RTx) allows for a reduced dose of CsA, to minimize the incidence of CsA-related side effects and to reduce costs. Therefore, 313 renal allograft recipients were randomized for treatment with MMF (1000 mg twice a day), prednisone, and either conventional- or low-dose CsA during the first 3 mo after RTx. The target trough levels were 300 and 150 ng/ml, respectively, during the first 3 mo and 150 ng/ml in both groups thereafter. A total of 313 patients were included: 161 patients received a conventional dose and 152 received a low dose of CsA. During the first 6 mo after RTx, graft failure or patient death occurred in 19 of 161 patients (12%) in the conventional-dose group and in 11 of 152 patients (7%) in the low-dose group (not significant). Biopsy-proven acute rejection occurred in 36 of 161 patients (22%) in the conventional-dose group and in 29 of 152 patients (19%) in the low-dose group (not significant). The incidence of delayed graft function was similar in both groups (31 of 161 [19%] versus 28 of 152 [18%]; not significant). Serum creatinine did not differ between the conventional- and the low-dose groups: 151 +/- 56 micromol/L versus 142 +/- 49 micromol/L at 3 mo and 141 +/- 60 micromol/L versus 136 +/- 49 micromol/L at 6 mo. There were no differences between the groups regarding BP, lipid metabolism, and infectious complications. In the low-dose group, an estimated $500 per patient was saved on the costs of CsA. In conclusion, the addition of MMF to CsA and prednisone after RTx allows the use of a lower-than-conventional dose of CsA, without increasing the risk of rejection.

Adrenal Cortex Hormones↗