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Biomedical subjects

J A Schulak

Publications and source records attributed to J A Schulak.

At least 19 recordsLinked to original sources
PubMed2005

Angiosarcoma arising in an arteriovenous fistula site in a renal transplant patient: a case report and literature review.

Angiosarcoma in the setting of immunosuppressed renal transplant recipients is exceedingly rare. In this report, we describe the occurrence of angiosarcoma arising at an arteriovenous fistula site of a 39-year-old renal transplant recipient that clinically mimicked a thrombosed aneurysm. These tumors are histologically high-grade and clinically aggressive malignancies. They have a predilection for arteriovenous fistula sites. The literature on this uncommon entity is reviewed and possible histogenesis is discussed.

Adult↗
PubMed2001

The use of the endothelin receptor antagonist, tezosentan, before or after renal ischemia protects renal function.

BACKGROUND: Utilization of organs subjected to ischemia/reperfusion (I/R) injury could expand the donor pool. Endothelin (ET) is implicated in renal I/R injury. Therefore, our study compared the effectiveness of pre- and postischemic administration of the ET receptor antagonist, Tezosentan, in preserving renal function. METHODS: In a rat model, a kidney was subjected to 45 min of ischemia along with a contralateral nephrectomy. After 24 hr of reperfusion, renal function was assessed by serum creatinine (Scr), inulin clearance (glomerular filtration rate; GFR), and histology. ET-1 peptide expression was localized using immunohistochemistry. Three groups were studied: I/R untreated (n=17), I/R pretreated (n=11), and I/R posttreated (n=13) with Tezosentan (15 mg/kg, i.v.). RESULTS: Tezosentan significantly decreased (P<0.05) the rise in Scr from I/R injury (2.0+/-0.4 mg/dl, before and 2.9+/-0.4 mg/dl, after treatment) compared with untreated animals (4.2+/-0.4 mg/dl). GFR was significantly increased (P<0.05) from 0.13+/-0.03 ml/min (untreated animals) to 0.74+/-0.16 and 0.47+/-0.14 ml/min (pre- and posttreated animals). Untreated animals had significant cortical acute tubular necrosis, which was almost completely prevented by pretreatment with Tezosentan and markedly reduced by posttreatment. Increased ET-1 peptide expression was noted in the renal vasculature and in the cortical tubular epithelium of kidneys exposed to I/R. CONCLUSIONS: The purpose of this study was to optimize the function of kidneys exposed to I/R injury. Pretreatment as well as posttreatment with Tezosentan successfully decreased Scr, increased GFR, and maintained renal architecture in kidneys after ischemia. Therefore, ET receptor antagonists may be useful to preserve renal function in the transplantation setting.

Animals↗
PubMed2001

Pneumoperitoneum upregulates preproendothelin-1 messenger RNA.

BACKGROUND: Laparoscopic pneumoperitoneum has been shown to decrease glomerular filtration rate (GFR) and urine volume (UV). Endothelin-1 (ET-1), a potent renal vasoconstrictor, has been implicated. The purpose of this study was to determine renal function, ET-1 gene expression, and peptide localization in kidneys subjected to CO2 pneumoperitoneum. METHODS: Experiments were performed in three groups of anesthetized Sprague-Dawley rats in which GFR and UV were measured before, during, and after insufflation. In the first group (n = 8), pneumoperitoneum (10 mmHg) was established for 30 min. The second group (n = 4) underwent a sham operation without pneumoperitoneum. In the final group (n = 4), kidneys were obtained from normal control animals without any prior surgical instrumentation. PreproET-1 (ppET-1) mRNA levels were measured by reverse transcription-polymerase chain reaction (RT-PCR). The ET-1 peptide was localized within kidneys by immunohistochemistry (IHC). RESULTS: Pneumoperitoneum caused a significant (p < 0.05) 87% decrease in GFR and a 79% decrease in UV from baseline, with a return to baseline values after desufflation. RT-PCR showed a significant (p < 0.05) increase in expression of ppET-1 mRNA in the laparoscopic group; it was 3.52 +/- 0.33 densitometric units (DU), as compared to 0.35 +/- 0.06 DU and 0.57 +/- 0.12 DU in the control and sham groups, respectively. IHC showed enhanced expression of the ET-1 peptide in the vascular endothelium and proximal tubular cells of the laparoscopic group compared to the control and sham groups. CONCLUSION: Pneumoperitoneum induces ET-1 gene and peptide upregulation in the kidney. Expression of ET-1 is increased in the renal vasculature and proximal tubular cells. The elevation of ET-1 and its localization may account for some of the renal dysfunction observed during pneumoperitoneum. This suggests that antagonism of ET-1 may be beneficial in patients with renal impairment undergoing prolonged laparoscopic procedures or in protecting allograft function during and after living donor nephrectomy.

Animals↗
PubMed2001

Immunomodulatory effect of extracorporeal photopheresis after successful treatment of resistant renal allograft rejection.

BACKGROUND: Acute renal allograft rejection contributes to patient morbidity. Standard immunosuppressives are only partially effective and have significant side effects. Extracorporeal photopheresis (ECP) has been effective in reversing the acute rejection process. T cell cytokine expression is implicated in rejection and tolerance but actual changes in the cytokine profile of ECP-treated individuals have not been documented. METHODS: ECP was administered to a patient with acute renal allograft rejection resistant to other immunosuppressives. Enzyme-linked immunosorbent spot (ELISPOT) assay was performed to determine the frequency of mitogen-induced cytokine-producing cells before and after ECP. RESULTS: ECP resulted in resolution of rejection; serum creatinine concentration fell from 7.1 to 2.2 mg/dl; ELISPOT revealed a three-fold increase in the frequency of IL-5 producing cells; IFN-gamma:IL-5 ratio shifted from 2.73 pre-treatment to 1.01 post-treatment. CONCLUSION: Effective therapy of acute allograft rejection with ECP alters the peripheral blood cytokine profile towards "type 2" cytokines, suggesting that alteration of T cell cytokine profiles may contribute to the resolution of the process.

Acute Disease↗
PubMed2001

Pancreas transplantation in Ohio: a 15-year outcomes analysis.

BACKGROUND: Beginning in 1984, all pancreas transplantations performed in the state of Ohio have been tracked by the Ohio Solid Organ Transplantation Consortium (OSOTC). In this study the outcomes of these transplantations were compared across 3 eras to determine whether increasing experience has been beneficial. METHODS: Between July 1984 and December 1999, 765 kidney-pancreas (KPTx) and 76 pancreas only (Ptx) transplantations were performed. Outcomes measures for these 841 pancreas transplantations were compared over 3 eras, 1984 to 1989, 1990 to 1994, and 1995 to 1999. RESULTS: One-year patient survivals for KPTx patients were 87%, 92%, and 94% in the 3 eras, respectively. Graft survival at 1 year was also markedly improved between era 1 and era 3, increasing for PTx patients from 21% to 85% and for KPTx patients from 68% to 85%. Average waiting time increased from 132 to 318 days between era 1 and era 3. Conversely, average length of stay in hospital was significantly decreased from 34 to 18 days. The cost of the procedure, as measured by hospital charges, also decreased when compared in 1985 dollars as a technique to control for inflation. CONCLUSIONS: These data suggest that pancreas transplantation in Ohio has become a very successful and cost-effective therapeutic intervention for patients with type I diabetes with or without concomitant end-stage renal failure.

Aged↗
PubMed2001

Abdominal catastrophe: definition and proposal for a new approach.

Abdominal catastrophe, defined as peritonitis from a visceral source, occurs in a significant number of patients treated by peritoneal dialysis. Peritonitis due to visceral injury is difficult to manage and is associated with high morbidity and mortality. Surgical intervention for both diagnosis and repair is definitive. However, no preventive strategy has been identified to date. The experience at University Hospitals of Cleveland and the published experiences of many other centers demonstrate that the risk of this complication has not changed in parallel with the many other improvements in the technique and outcome of peritoneal dialysis. We propose an approach to improve the understanding and outcome of this devastating complication. First, classification of peritonitis by source, not by organism, may lead to a more focused response to each episode of peritonitis. Second, the importance of antibiotic prophylaxis should be re-assessed in defined clinical settings that have a high likelihood of progressing to abdominal catastrophe. Third, optimal antibiotic regimens need to be devised and applied when visceral injury is highly suspected as a cause of peritonitis. Finally, the results of surgical interventions must be carefully studied.

Humans↗
PubMed2000

Hypertension after pancreas-kidney transplantation: role of bladder versus enteric pancreatic drainage.

BACKGROUND: Recent reports suggest that hypertension may be less common after simultaneous pancreas-kidney transplantation than after kidney transplantation alone. However, the mechanisms for this beneficial effect have not been delineated. We hypothesize that lower blood pressures may result from chronic volume depletion in patients with bladder-drained pancreatic allografts. METHODS: We compared the incidence and severity of hypertension 12 months after transplantation in 79 bladder-drained pancreas-kidney recipients and 46 diabetic kidney-only recipients. These two groups were compared with a smaller group of enterically drained pancreas-kidney recipients. Blood pressure was also compared before and after surgical conversion from bladder to enteric drainage in 10 patients. RESULTS: Hypertension was significantly less common and less severe after pancreas-kidney transplantation than after kidney transplantation alone, but the benefit of the pancreas transplant was evident only in bladder-drained patients. Logistic regression analysis of the bladder-drained pancreas-kidney patients confirmed the independent impact of the pancreatic allograft on the presence of hypertension, indicated an independent association with serum creatinine concentration and donor age, but suggested no correlation with recipient age, race, or number of rejection episodes. A comparison of blood pressures before and after pancreatic conversion from bladder to enteric drainage indicated no significant change in the prevalence or severity of hypertension. CONCLUSIONS: We conclude that the beneficial effect of a pancreas transplant on the prevalence and severity of hypertension after simultaneous pancreas-kidney transplantation is limited to bladder-drained patients. Although it is possible that the effect is mediated by chronic volume depletion, the observation that blood pressure does not increase after conversion from bladder to enteric drainage suggests that other factors may be involved.

Adult↗
PubMed1999

The effect of the volume of procedures at transplantation centers on mortality after liver transplantation.

BACKGROUND AND METHODS: For many complex surgical procedures there is an association between a low volume of procedures and an increased risk of death for the patients who undergo the procedures. We examined the effect of the volume of procedures at transplantation centers on the risk of death after liver transplantation. We analyzed all liver transplantations performed in the United States between October 1, 1987, and April 30, 1994. Because the results for 1987 to 1991 were largely similar to those from 1992 to 1994, we focused on the more recent period. RESULTS: Between January 1, 1992, and April 30, 1994, 47 centers performed 20 or fewer liver transplantations each per year (total, 837 transplantations) and were designated low-volume centers, and 52 centers performed more than 20 transplantations each per year (total, 6526) and were designated high-volume centers. The one-year mortality rate for the low-volume centers was 25.9 percent, as compared with 20.0 percent for the high-volume centers. Thirteen centers, all of which had low volumes, had one-year mortality rates of more than 40 percent. Low-volume centers that were affiliated with high-volume centers, such as pediatric transplantation programs, had results similar to those of the high-volume centers. The one-year mortality rate at unaffiliated low-volume centers was 28.3 percent, as compared with a rate of 20.1 percent for the group of all high-volume centers plus affiliated low-volume centers (P<0.001). CONCLUSIONS: As a group, liver-transplantation centers in the United States that perform 20 or fewer transplantations per year have mortality rates that are significantly higher than those at centers that perform more than 20 transplantations per year. Information regarding the outcome of liver transplantation at transplantation centers should be made widely available to the public in a timely manner.

Hospitals, Special↗
PubMed1999

Pretransplant frequency of donor-specific, IFN-gamma-producing lymphocytes is a manifestation of immunologic memory and correlates with the risk of posttransplant rejection episodes.

While matching for MHC Ags improves renal allograft survival, closely matched grafts sometimes fail due to rejection, and poorly matched allografts are often well tolerated by the recipient. The severity of the rejection process may partially depend on the presence of environmentally primed T cells in the recipient that cross-react with donor Ags. To test for the presence of primed, donor-specific T cells in humans before transplantation, we used an enzyme-linked immunospot assay for detection of allospecific cytokines produced by individual human PBLs. We demonstrate that this approach detects cytokine production at single cell resolution and detects production of IFN-gamma only when there is defined immunologic priming, thus representing a measure of primed donor-specific immunity. Because the environmental Ag exposure of the recipient is not a function of the HLA mismatch between donor and potential recipient, the number of HLA mismatches may not correlate with the frequency of pretransplant, donor-specific IFN-gamma-producing PBLs. Studies of donor-specific IFN-gamma-producing lymphocytes in a cohort of patients being evaluated for renal transplantation corroborated this hypothesis. Moreover, for recipients of both living and cadaver renal allografts, the pretransplant frequency of donor-specific memory cells correlated with the posttransplant risk of developing acute rejection episodes. This improved ability to define the strength of the allospecific immune response by enzyme-linked immunospot assay may allow improved pairing of recipients with donors and identification of kidney allograft donor-recipient pairs at high risk for acute rejection, thus permitting targeted interventions aimed at prolonging graft survival.

Acute Disease↗
PubMed1999

Cold ischemia induces endothelin gene upregulation in the preserved kidney.

BACKGROUND: Prolonged cold ischemia time (CIT) can lead to posttransplant renal dysfunction; however, the pathophysiology remains unclear. Endothelin (ET), a potent vasoconstrictive peptide, may play a role in this injury. The purpose of this study was to determine if cold ischemia could induce renal ET-1 gene upregulation and to localize ET-1 peptide expression in the hypothermic kidney. MATERIALS AND METHODS: Kidneys from Lewis rats were perfused with Viaspan, harvested, and stored at 4 degrees C for varying periods of CIT: 0, 6, 24, and 48 h. Preproendothelin-1 (ppET-1) gene upregulation was measured using a reverse-transcription polymerase-chain reaction. ET-1 peptide expression was localized using immunohistochemistry. RESULTS: Control kidneys (0 h CIT) had 0. 56 +/- 0.22 DU of ppET-1 mRNA. After 6 h of CIT, a 2.3-fold increase in this level was noted. Following 24 h of CIT, ppET-1 mRNA was significantly upregulated to 1.96 +/- 0.38 DU (P < 0.05). Immunohistochemistry revealed typical vascular ET-1 staining in control kidneys. At 6 h of CIT, a significant increase in the expression of ET-1 was noted in the peritubular capillaries and vasa recta. After 24 h, intense staining for ET-1 was seen in the medullary collecting ducts. After 48 h of CIT, early cellular necrosis was present along with global decreases in ET-1 expression and ppET-1 mRNA levels. CONCLUSIONS: This study demonstrates that 24 h of cold preservation can induce significant upregulation of the renal ET-1 gene and increase expression of the ET-1 peptide localized to both vascular endothelial and tubular epithelial surfaces of the kidney. Consequently, prolonged cold ischemia prior to transplantation may lead to delayed renal function following revascularization via endothelin-induced vasoconstriction and/or tubular impairment.

Animals↗
PubMed1999

Endothelin up-regulation and localization following renal ischemia and reperfusion.

BACKGROUND: Endothelin (ET), a potent vasoconstrictor, is known to play a role in ischemic acute renal failure. Although preproET-1 (ppET-1) mRNA is known to be up-regulated following ischemia/reperfusion injury, it has not been determined which component of the injury (ischemia or reperfusion) leads to initial gene up-regulation. Likewise, although ET-1 peptide expression has been localized in the normal kidney, its expression pattern in the ischemic kidney has not been determined. Therefore, the purpose of this study was twofold: (a) to determine whether ischemia alone or ischemia plus reperfusion is required for the up-regulation of ppET-1 mRNA to occur, and (b) to localize ET-1 peptide expression following ischemia in the rat kidney to clarify better the role of ET in the pathophysiology of ischemia-induced acute renal failure. METHODS: Male Lewis rats underwent clamping of the right renal vascular pedicle for either 30 minutes of ischemia (group 1), 60 minutes of ischemia (group 2), 30 minutes of ischemia followed by 30 minutes of reperfusion (group 3), or 60 minutes of ischemia followed by three hours of reperfusion (group 4). The contralateral kidney acted as a control. ppET-1 mRNA up-regulation and ET-1 peptide expression were examined using the reverse transcription-polymerase chain reaction and immunohistochemistry, respectively. RESULTS: Reverse transcription-polymerase chain reaction yielded a control (nonischemic) value of 0.6 +/- 0.2 densitometric units (DU) of ppET-1 mRNA in the kidney. Group 1 levels (30 min of ischemia alone) were 1.8 +/- 0.4 DU, a threefold increase (P < 0.05). Group 2 levels (60 min of ischemia alone) increased almost six times above baseline, 3.5 +/- 0.2 DU (P < 0.01), whereas both group 3 and group 4 (ischemia plus reperfusion) did not experience any further significant increases in mRNA levels (1.9 +/- 0.4 DU and 2.8 +/- 0.6 DU, respectively) beyond levels in group 1 or 2 animals subjected to similar ischemic periods. ET-1 peptide expression in the ischemic kidneys was significantly increased over controls and was clearly localized to the endothelium of the peritubular capillary network of the kidney. CONCLUSIONS: Initial ET-1 gene up-regulation in the kidney occurs secondary to ischemia, but reperfusion most likely contributes to sustaining this up-regulation. The marked increase of ET-1 in the peritubular capillary network suggests that ET-induced vasoconstriction may have a pathophysiological role in ischemic acute tubular necrosis.

Acute Kidney Injury↗
PubMed1999

Azathioprine monotherapy in HLA-identical live donor kidney transplant recipients.

The high success rate of HLA-identical sibling transplants and our previous experience with steroid-free immunosuppressive regimens and cyclosporine withdrawal prompted us to evaluate the safety and efficacy of monotherapy with azathioprine in 12 HLA-identical kidney transplant recipients with a serum creatinine concentration less than 176.8 mumol/L, a 1-way stimulatory index less than 2.0 in a post-transplant mixed lymphocyte culture, and a demonstrated tolerance of a minimum azathioprine dose of 1.0 mg/kg per day without leukopenia. Eleven of 12 patients were successfully converted to azathioprine monotherapy without a significant change in serum creatinine concentration for as long as 76 months. Benefits of steroid and cyclosporine withdrawal included a significant reduction in mean systolic and diastolic blood pressure, number of blood pressure medications, total serum cholesterol, and glycohemoglobin in diabetic subjects. Our results suggest that azathioprine monotherapy is safe and effective in a select group of HLA-identical sibling transplants, but these benefits must be carefully balanced against an associated risk of precipitating acute allograft rejection.

Adult↗
PubMed1998

Resolution of spur cell anemia with liver transplantation: a case report and review of the literature.

Spur cell anemia is an acquired hemolytic anemia, characterized by an increased percentage of abnormally shaped erythrocytes that are known as acanthocytes. The erythrocytes have numerous spicules irregularly distributed over the cell surface. Spur cell anemia has been described to occur in several conditions, including cirrhosis. We present an unusual case of a young patient with hemochromatosis, alcohol abuse, decompensated cirrhosis, and spur cell anemia who had a spontaneous resolution of the spur cell anemia after orthotopic liver transplantation. This finding suggests that the diseased liver may contribute to transformation of the erythrocyte to the spur cell.

Adult↗
PubMed1998

Resolution of hepatitis B viremia in a renal transplant recipient treated with alpha-2b interferon.

A renal transplant patient developed symptomatic hepatitis after withdrawal from corticosteroids. Tests for hepatitis B e antigen and hepatitis B viral DNA were both positive prior to treatment with 1 million units alpha interferon three times weekly for 3 weeks followed by an increase to 3 million units alpha interferon three times weekly for a total of 16 weeks. At the end of treatment, hepatitis had clinically resolved with conversion to a hepatitis B e antibody positive and hepatitis B e antigen and viral DNA negative state. The renal allograft function remained excellent throughout the course of therapy with interferon.

Adult↗
PubMed1998

Benefits of pre-emptive dose reduction for Sandimmune to Neoral conversion in stable renal transplant recipients.

In an effort to minimize nephrotoxicity resulting from greater exposure to cyclosporine after Sandimmune to Neoral conversion, we compared two conversion regimens using different dosing ratios. Serial serum creatinine concentrations and trough cyclosporine levels were measured in 26 patients converted from Sandimmune to Neoral using a 1:0.8 dosing ratio (Group 1) and compared to those of 26 patients converted using a 1:1 dosing ratio (Group 2). The percentage change in peak serum creatinine concentration after conversion was greater in Group 2. However, at last follow-up, the dose reductions in each group were comparable. Following conversion, patients in Group 1 required fewer dose adjustments and follow-up blood tests. Compared to conversion using a 1:1 dosing ratio, conversion from Sandimmune to Neoral using a 1:0.8 ratio results in comparable dose reductions and less short-term nephrotoxicity, while requiring less frequent laboratory monitoring.

Adult↗
PubMed1997

Long-term renal function in type I diabetics after kidney or kidney-pancreas transplantation: influence of number, timing, and treatment of acute rejection episodes.

BACKGROUND: Previous studies comparing renal function in diabetic subjects receiving either a kidney or kidney-pancreas transplant generally have indicated no differences; however, these studies have been limited by inclusion of either a small number of patients or selected patients followed for relatively short periods of time. METHODS: To compare long-term renal function and factors affecting renal function in type I diabetic patients receiving either kidney or kidney-pancreas transplants, the slopes of regression lines generated by plotting the reciprocal of serum creatinine (1/Cr) versus time were measured in 109 consecutive patients followed for at least 12 and up to 102 months after transplantation. Multivariate analyses included linear regression using the slope of 1/Cr versus time as the dependent variable and logistic regression using a positive or negative slope as the dependent variable. RESULTS: Significant differences between kidney-pancreas (n=64) and kidney recipients (n=45) included a smaller proportion of African-Americans, lower rates of HLA matching, lower levels of panel-reactive antibodies, shorter cold ischemia times, a lower incidence of delayed graft function, and a higher incidence of acute renal allograft rejection episodes in the kidney-pancreas group. Trough cyclosporine blood levels were significantly higher in the kidney-pancreas group for the first 12 posttransplant months. The slopes of 1/Cr versus time were negative in each group with a trend toward a more negative slope in the kidney-pancreas group. Multivariate analyses indicated that a concomitant pancreas allograft did not influence long-term renal function. The total number of renal rejection episodes was the best independent predictor of a negative slope of 1/Cr versus time. However, use of OKT3 for the treatment of rejection within the first 3 months of transplantation exerted a surprisingly beneficial effect on long-term renal function, a phenomenon that was most apparent in the kidney-alone group. CONCLUSIONS: The frequency and timing of acute rejection episodes are more important than the influence of a simultaneously transplanted pancreatic allograft in determining long-term function of the transplanted kidney. A concerning trend toward late deterioration of renal function in kidney-pancreas recipients suggests that the benefits of sustained euglycemia, shorter cold ischemia times, lower rates of sensitization, and early use of OKT3 ultimately may be outweighed by the negative effects of more frequent renal rejection episodes.

Acute Disease↗
PubMed1997

Renal transplantation using a kidney with a large benign cyst.

We report a case in which a living donor kidney that contained a large benign cyst was successfully transplanted between a mother and her daughter. The donor, a 53-year-old woman, had good renal function, but her right kidney contained a large 4-cm cyst that had a benign appearance on computed tomography. At operation the cyst was proven to be benign by frozen-section histological examination and the transplant was performed. Both donor and recipient continue to enjoy satisfactory renal function 3 years after transplantation. A review of the literature regarding renal cysts and management strategies for use of cystic kidneys in transplantation are presented.

Adult↗