Biomedical subjects

E A Kouwenhoven

Publications and source records attributed to E A Kouwenhoven.

16 recordsLinked to original sources

PubMed2005

Fear for the intraabdominal abscess after laparoscopic appendectomy: not realistic.

BACKGROUND: The risk for intraabdominal abscess (IAA) after laparoscopic appendectomy (LA) is still a matter of debate. The aim of the present study was to evaluate postoperative complications after open (OA) and laparoscopic appendectomy, in particular in perforated appendicitis (PA). METHODS: In the period 1999-2002, 331 appendectomies were performed for histological proven appendicitis, 144 by the open and 187 by the laparoscopic technique. Parameters were conversion rate, perforation, wound infection, and IAA. RESULTS: Conversion to OA was done in 20 cases (10.7%). Perforated appendicitis led more frequently to conversion than simple appendicitis (23.5 vs 7.8%; p = 0.007). Perforated appendicitis was equally seen in the open and laparoscopic technique (15 vs 18%). Wound infections after OA, converted and LA for acute appendicitis were 3 of 144 (2.1%), 1 of 20 (5.0%) and 1 of 167 (0.6%), respectively (NS). IAA formation did not differ among the three procedures (3.5 vs 0 vs 3.6%). In PA the rate of IAA formation was increased. However, the risk was not influenced by the technique: Two patients after the OA, none after a converted procedure, and two patients after LA formed an abscess (9.5 vs 0 vs 7.7% [NS]). CONCLUSION: LA does not lead to more intraabdominal abscesses than the open technique; even for perforated appendicitis the laparoscopic technique can be used safely.

Abdominal Abscess↗

PubMed2001

Transplantation of a single kidney per se does not lead to late graft dysfunction.

In unraveling the pathogenesis of chronic transplant dysfunction (CTD), non-alloantigen specific factors, as ischemia/reperfusion and renal mass have been suggested to play a role in the process. The aim of the present study was to investigate the effect of the transplantation procedure per se on the development of CTD in a syngeneic kidney transplant model in the rat. Kidney transplantation was performed with the BN rat as donor and recipient, the recipient kidneys having been removed. Unilaterally nephrectomized (UNx) and native BN rats served as controls. Renal function was determined monthly (proteinuria and glomerular filtration rate/100 g body weight; GFR). The follow-up period was until 52 weeks post-transplantation. Histomorphological analysis of CTD according to the BANFF criteria was carried out. Immunohistochemical staining was performed to identify infiltrating cells (CD4, CD8, and ED1) and the expression of MHC class II and ICAM-1. Isografts had a minor, constant proteinuria during follow-up, which did not differ from that of UNx: 27 +/- 10 vs. 29 +/- 2 mg/24 h at week 52. Unilateral nephrectomy led to a significant reduction of the GFR, which was about 80% of that of native rats. The GFR of isografts did not differ from that of UNx rats. Histomorphology of renal isografts was comparable to UNx and native kidneys; some glomerulopathy and tubular atrophy leading to a total BANFF-score of 2.6 +/- 0.5. In native BN kidneys, few CD4+ cells and ED-1+macrophages (mphi) were found; MHC class II was constitutively expressed on the proximal tubules and ICAM-1 on the glomeruli and peritubular capillaries. UNx-kidneys showed a similar pattern. Isografts had significantly more CD4+ cells and Mphi, mainly localized in the glomeruli, and a more intense ICAM-1 expression in the glomeruli and interstitium. Transplantation of one kidney in itself does not lead to CTD.

Animals↗

PubMed2001

Cold ischemia augments allogeneic-mediated injury in rat kidney allografts.

BACKGROUND: Some clinical studies demonstrate that kidney grafts with prolonged cold ischemia experience early acute rejection more often than those with minimal ischemia. The mechanism, however, is putative. Therefore, the aim of this study was to unravel the impact of ischemia on the immune response in rat kidney allografts compared with that in isografts. METHODS: To induce ischemic injury, donor kidneys were preserved for 24 hours in 4 degrees C University of Wisconsin solution before transplantation. No immunosuppression was administered. The histomorphology according to the BANFF criteria for acute rejection and infiltrating cells were assessed at days 1, 2, 3, 4, 6, and 8 post-transplantation. RESULTS: In allografts, exposure of the kidney to ischemia led to a significantly earlier onset of interstitial cell infiltration and tubulitis compared with nonischemic allografts. The BANFF score of interstitial cell infiltration was 1 +/- 0 vs. 0.25 +/- 0.29 at day 3 and 2 +/- 0 vs. 1.25 +/- 0.25 at day 4. In contrast, in isografts, the effect of ischemia on the histology was not significant. From day 6, the histologic differences between ischemic and nonischemic grafts disappeared. Ischemia led to a more intense expression of P-selectin (day 1), intercellular adhesion molecule-1 (ICAM-1; day 2), and major histocompatibility complex (MHC) class II on endothelium and proximal tubular cells (day 2) in both allografts and isografts. Concurrently with the up-regulated ICAM-1 and MHC expression, significantly more CD4(+) cells and macrophages infiltrated the ischemic allografts at days 2 and 3 and the ischemic isografts at day 4. Importantly, the influx of these cells after ischemia was significantly greater in allografts than in isografts. CONCLUSIONS: Cold ischemia augments allogeneic-mediated cell infiltration in rat kidney allografts. The earlier onset of acute rejection in 24-hour cold preserved allografts may be prevented by better preservation or treatment using tailored immunosuppression.

Animals↗

PubMed2001

Ureteroneocystostomy contributes to late functional and morphological changes in rat kidney transplants.

PURPOSE: We investigated whether the surgical technique used to reconstruct the ureter has an impact on the late function of kidney transplants by comparing ureteroneocystostomy and ureteroureterostomy. To rule out alloantigeneic mediated effects on late graft dysfunction kidney transplants were performed in a syngeneic model. MATERIALS AND METHODS: Rat kidney isografts were transplanted with simultaneous ureteroneocystostomy or ureteroureterostomy. Unilaterally nephrectomized rats served as controls. Eight weeks after transplantation intrapelvic pressure was measured during baseline diuresis, and after intravesical and intrapelvic infusion. Albuminuria was determined monthly until sacrifice at week 52. Histomorphological analysis included the degree of glomerulopathy, tubular atrophy, interstitial fibrosis and intimal hyperplasia. CD4+- and CD8+ T cells, and macrophages were identified using immunohistochemical testing. RESULTS: Eight weeks after transplantation intrapelvic pressure during baseline diuresis and after intrapelvic infusion was significantly increased in rats with ureteroneocystostomy versus those with ureterostomy and unilateral nephrectomy, whereas intravesical infusion did not change the pressure in any group. During followup albuminuria after ureteroureterostomy did not differ from that after unilateral nephrectomy. In contrast, albuminuria significantly increased after ureteroneocystostomy from week 36 onward. At week 52 the ureter and kidney after ureteroureterostomy and unilateral nephrectomy had a normal appearance, whereas all ureters were dilated after ureteroneocystostomy. Nevertheless, 6 of the 8 kidneys in the ureteroneocystostomy group had a normal appearance. However, histomorphological findings in rats with transplants and ureterovesical anastomosis demonstrated significantly more interstitial fibrosis, CD8+ T cells and macrophages than isografts ureteroureterostomy. CONCLUSIONS: As a surgical technique for restoring the urinary tract after kidney transplantation, ureteroneocystostomy contributes to the development of long-term functional and histological renal changes. Partial obstruction may be the cause of this renal impairment.

Albuminuria↗

PubMed2000

Functional, histological, and inflammatory changes in chronically rejecting small bowel transplants.

Our aim was to develop a model of chronic rejection (CR) in small bowel allografts, and to study the changes occurring in these grafts. Small bowel transplantation was performed using the DA to AS rat strain combination. Short-term (5 mg/kg intramuscular, from days -2 to +9), or long-term cyclosporin treatment (5 mg/kg, 3 times a week until day 50) was given to prevent acute rejection. Controls were untreated allografts, DA isografts with and without cyclosporin, and normal DA and AS rats. They were followed for 50 and 100 days after transplantation. Recipients of a syngeneic graft lost weight during the first week after transplantation, but started to regain weight and kept growing thereafter. Histology showed normal bowel architecture with normal mesenteric lymph nodes and Peyers patches. Vigorous acute rejection occurred in the untreated allografts. Animals had persistent weight loss, and were killed between 6-13 days after transplantation. No clinical signs of graft-versus-host disease were seen. Histology showed end-stage acute rejection. In both cyclosporin-treated allografted groups the postoperative course was as in the isografted animals. However, all animals had histologic signs of CR by 50 and 100 days after transplantation. Changes were most prominent in the mesentery. Serositis with increased vascularity, inflammation with sclerosis, and patchy myointimal proliferation with endothelialitis of the mesenteric vessels were found. Changes in the bowel were patchy and included some thickening of the muscle coat, crypt hyperplasia, scattered necrotic cells in the crypts, slight blunting of villi and loss of goblet cells. Infiltrating cells in the mesentery and bowel consisted mainly of CD 4+ cells, CD 8- T-cells and monocytes/macrophages. Lactulose-mannitol urinary excretion ratio was significantly increased in short-term cyclosporin treated allografts at days 50 and 100 posttransplant. Serum albumin levels were significantly lowered in this group at both time points examined. We developed two models in which CR occurs after small bowel transplantation. Long-term cyclosporin treatment delayed the development of CR, since functional abnormalities were only seen in the animals that were treated with short-term cyclosporin.

Animals↗

PubMed2000

Negligible role for NK cells and macrophages in delayed xenograft rejection.

Hyperacute rejection (HAR) of a discordant xenograft can be avoided by complement manipulation, but delayed xenograft rejection (DXR) still leads to graft loss. It is generally assumed that macrophages and NK cells play key roles in DXR. In the present study the survival times and cellular infiltrate following guinea pig to rat heart transplantation was analyzed in the course of DXR, following aspecific and specific manipulation of macrophages and NK cells. HAR was overcome by a single injection of cobra venom factor 1 day before heart transplantation. To aspecifically reduce the inflammatory response dominating DXR, dexamethasone (DEXA) was given. Treatment with DEXA markedly reduced infiltration by NK cells, macrophages, and granulocytes. It also led to prolonged graft survival times (median survival of 0.4 days, n = 10, P < 0.05). In the second series of experiments the specific roles of NK cells and macrophages in DXR were further assessed. Monoclonal antibody 3.2.3 was used to selectively deplete NK cells. Liposome-encapsulated dichloromethylene biphosphonate was given to achieve macrophage depletion. Neither of these specific treatments, alone or combined, led to prolonged graft survival. Immunohistology revealed that at day 2 after transplantation no NK cells or macrophages were present in grafts from the combined treatment group. Only a mild infiltration of granulocytes was observed. Collectively, these results strongly suggest that NK cells and macrophages are not likely to be pivotal cell types in DXR.

Animals↗

PubMed2000

Etiology and pathophysiology of chronic transplant dysfunction.

Chronic transplant dysfunction (CTD) is the predominant cause of late graft failure. The common histopathological feature in all transplanted organs is intimal hyperplasia accompanied by organ specific lesions. The knowledge about CTD is incomplete, and there is no therapy to prevent or treat it. This review describes the current knowledge on the etiology of CTD, with emphasis on kidney transplants, and postulates a pathophysiologic route through which CTD may develop.

Acute Disease↗

PubMed1999

Late graft dysfunction after prolonged cold ischemia of the donor kidney: inhibition by cyclosporine.

BACKGROUND: The present study was devised to elucidate the influence of prolonged cold ischemia on the development of chronic transplant dysfunction (CTD) in kidney isografts (Brown Norway-->Brown Norway; BN-->BN) and in kidney allografts (BN-->Wistar Agouti/ Rij [WAG]) under temporary cyclosporine (CsA) therapy. METHODS: To induce ischemic injury, BN donor kidneys were preserved for 24 hr in 4 degrees C University of Wisconsin solution before transplantation. Renal function (proteinuria), histomorphology according to the BANFF criteria for CTD, and infiltrating cells were assessed. Grafts were examined both early at days 2, 3, 6, and 10, and late at week 26 (allografts) or at week 52 (isografts). RESULTS: Nonischemic isografts preserved a normal function and morphology. Ischemic isografts developed a progressive proteinuria over time and demonstrated significantly more glomerulopathy with macrophage (Me) infiltration and intimal hyperplasia than nonischemic controls at week 52. During the initial 10 days, there was an increased infiltration of MHC class II+ cells, predominantly CD4+ cells and Mphi, coinciding with up-regulated intercellular adhesion molecule-1 expression. CsA treatment in ischemic isografts inhibited infiltration of MHC II+ cells in the early stage, which was accompanied by significantly less renal damage at week 52 compared with untreated controls (proteinuria: 59+/-8 vs. 134+/-19 mg/24 hr; BANFF score: 2.8+/-0.4 vs. 4.3+/-1.0). Under CsA therapy, 24-hr cold ischemia of the allograft affected neither the onset or progress of proteinuria, nor the histomorphology (BANFF score: 7.8+/-2.4 vs. 7.3+/-1.9). In both ischemic and nonischemic allografts, intercellular adhesion molecule-1 expression and mononuclear cell infiltration (CD4, CD8, Mphi was abundantly present during the first 10 days and function deteriorated rapidly. CONCLUSIONS: Prolonged cold ischemia plays a role in the induction of CTD, but its deleterious effect can be successfully inhibited by CsA. Therefore, the alloantigeneic stimulus is the overriding component in the multifactorial pathogenesis of CTD.

Adenosine↗

PubMed1999

Increased expression of basic fibroblast growth factor during chronic rejection in intestinal transplants is associated with macrophage infiltrates.

Long-term survival of intestinal transplants is hampered by chronic rejection (CR). Since transplants with CR demonstrate fibrotic changes, the cytokine basic fibroblast growth factor (bFGF) may be involved in the tissue remodelling of chronic intestinal rejection. The aim of this study was to investigate the bFGF gene and protein expression and distribution in chronically rejecting intestinal allografts. Orthotopic small bowel transplantation was performed in the allogeneic DA-to-AS rat combination. Cyclosporin was administered temporarily to prevent acute rejection. Controls were DA isografts and normal DA. bFGF gene expression was evaluated using reverse transcriptase polymerase chain reaction (RT-PCR) of the ileum RNA and was standardized against Glyceraldehyde-3-phosphate-dehydrogenase (GAP-DH) expression. bFGF protein was determined using immunohistochemistry. To identify the bFGF-positive cell type, sequential sections were stained for cell markers. Allografts showed histological features of CR, whereas isografts preserved normal architecture. bFGF gene expression was present in normal ileum and significantly upregulated in allografts. Immunohistochemical staining showed a significant increase in bFGF protein compared to isografts. Most bFGF-positive cells were localized in the submucosa and muscularis, particularly around the neural plexus. bFGF-positive cells appeared to be ED-2-positive macrophages, strongly suggesting that the site of bFGF production is the activated macrophage. This study demonstrates increased bFGF mRNA and protein in chronically rejecting intestinal allografts that appear to be produced by macrophages.

Animals↗

PubMed1999

Genetic susceptibility of the donor kidney contributes to the development of renal damage after syngeneic transplantation.

Solitary kidneys, especially in rats, appear vulnerable to develop functional and structural damage. However, differences in susceptibility exist between strains. It is not clear whether this is intrinsic to the kidney or due to environmental factors. Therefore, the aim of the present study was to investigate possible differences in genetic susceptibility for renal damage. By transplanting different rat donor kidneys into a normotensive, histocompatible recipient, the kidneys were exposed to the same blood pressure profiles, metabolic and hormonal environment. Kidneys from young adult hypertensive fawn-hooded (FHH) rats, a strain showing early onset renal damage, normotensive, renal damage-resistant August x Copenhagen-Irish (ACI), and (ACI x FHH) F1 donors were transplanted into male F1 recipients. The native kidneys of the recipients were removed 1 week after transplantation. The results were mutually compared and to their unilaterally nephrectomized littermates. Systolic blood pressure (SBP) and albuminuria (UaV) were determined at the time of transplantation and at 8 and 16 weeks. The histomorphologic analysis included the incidence of focal glomerulosclerosis (FGS), and determination of chronic transplant dysfunction according to the BANFF criteria. A negative impact of the transplantation technique in this syngeneic situation could not be detected as F1 transplants did not differ functionally and morphologically from their UNx controls. Transplanting an ACI kidney did not result in significant changes of SBP, UaV, and incidence of FGS compared to F1 transplants and ACI-UNx. In contrast, FHH kidneys did show a progressive increase of UaV and glomerulosclerosis and a significantly higher BANFF score, whereas the SBP did not differ from F1 transplants. The moderate hypertension seen in FHH did not travel with the kidney. Compared to the FHH-UNx rats, transplantation of a FHH kidney did significantly attenuate the increase of UaV and FGS. The susceptibility of the donor kidney appears to be an important factor in the development of chronic renal damage. This may play a role in the long-term functional changes seen after clinical renal transplantation.

Albuminuria↗

PubMed1999

EGF and TGF-beta1 gene expression in chronically rejecting small bowel transplants.

Long-term survival of small bowel transplants is hampered by chronic rejection. Epidermal growth factor (EGF) and transforming growth factor beta (TGF-beta) have opposing, regulatory roles in normal intestinal physiology and may be involved in the pathogenesis of chronic intestinal rejection. Our aim was to investigate the expression of EGF and TGF-beta1 in chronically rejecting small bowel transplants. Orthotopic small bowel transplantation was performed in the allogeneic DA-to-AS rat combination; Cyclosporin was administered temporarily to prevent acute rejection. Controls were DA isografts and normal DA rats. PreproEGF and TGF-beta1 gene expression was evaluated by northern blot analysis of the ileum RNA and standardized against glyceraldehyde-3-phosphate-dehydrogenase expression. Allografts demonstrated functional impairment and histological features of chronic rejection, whereas isografts appeared normal. Allografts demonstrated a significant reduction of EGF mRNA when compared to DA isografts. No significant changes were detected in TGF-beta1 expression in either allogeneic or syngeneic grafts. In conclusion, this study demonstrates reduced preproEGF and preserved TGF-beta1 gene expression in chronically rejecting small bowel transplants.

Analysis of Variance↗

PubMed1997