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J D Punch

Publications and source records attributed to J D Punch.

At least 19 recordsLinked to original sources
PubMed2006

Characteristics associated with liver graft failure: the concept of a donor risk index.

Transplant physicians and candidates have become increasingly aware that donor characteristics significantly impact liver transplantation outcomes. Although the qualitative effect of individual donor variables are understood, the quantitative risk associated with combinations of characteristics are unclear. Using national data from 1998 to 2002, we developed a quantitative donor risk index. Cox regression models identified seven donor characteristics that independently predicted significantly increased risk of graft failure. Donor age over 40 years (and particularly over 60 years), donation after cardiac death (DCD), and split/partial grafts were strongly associated with graft failure, while African-American race, less height, cerebrovascular accident and 'other' causes of brain death were more modestly but still significantly associated with graft failure. Grafts with an increased donor risk index have been preferentially transplanted into older candidates (>50 years of age) with moderate disease severity (nonstatus 1 with lower model for end-stage liver disease (MELD) scores) and without hepatitis C. Quantitative assessment of the risk of donor liver graft failure using a donor risk index is useful to inform the process of organ acceptance.

Adolescent↗
PubMed2005

Preliminary analysis of early outcomes of a prospective, randomized trial of complete steroid avoidance in liver transplantation.

Steroids are a mainstay in liver transplantation for induction and maintenance immunosuppression but are associated with significant adverse effects. While prior studies have successfully limited the use of steroids, whether complete steroid avoidance will improve outcomes remains unclear. To further evaluate the need for steroids, consenting patients who underwent liver transplantation between June 2002 and May 2004 were entered into a prospective, randomized trial to receive either standard therapy (tacrolimus, mycophenolate mofetil, steroid induction/maintenance) or complete steroid avoidance (standard therapy without steroid induction/maintenance). Clinically suspected rejection was confirmed by biopsy and treated with pulse steroid therapy. Outcomes were compared on an intention to treat basis. Of the 72 patients enrolled, 36 (50%) were randomized to the steroid avoidance group with a mean follow up of 412 +/- 41 days. Donor and recipient characteristics were similar between groups. The steroid avoidance group was more likely to have significant infections (52% vs 28%, P = .03). There was a trend toward an increased rate of acute rejection (25% vs 14%, P = .23). Twelve of 36 recipients (33%) enrolled in the steroid avoidance group later received steroids. The incidence of recurrent hepatitis C was similar between groups. The 1-year patient (90% vs 83%, P = .44) and graft survivals (90% vs 81%, P = .27) were similar between groups. These data suggest complete steroid avoidance in liver transplantation results in acceptable patient and graft survival. However, the potential long-term benefits of steroid avoidance, including a decrease in severity of recurrent hepatitis C, remain under investigation.

Adrenal Cortex Hormones↗
PubMed2003

Successful surgical salvage of partial pancreatic allograft thrombosis.

BACKGROUND: Venous thrombosis remains an important cause of pancreatic graft loss. Nevertheless, reports are scarce of treatment alternatives to complete graft removal. We describe a case of surgical salvage of a partial pancreatic graft thrombosis. METHODS: We used descriptive retrospective analysis. RESULTS: A 36-year-old patient with juvenile-onset diabetes mellitus and previous living related renal transplant received a cadaveric pancreas transplant in the right iliac fossa with enteric exocrine drainage and standard vascular anastomosis. Two days after discharge from the hospital, he presented with severe right upper quadrant pain, nausea, vomiting, fever, and leukocytosis. He was taken to the operating room for exploration. The tail of the pancreas, which was kinked under the gallbladder, was necrotic and excised. The remainder of the pancreas looked normal. The patient recovered well from surgery and was discharged home 7 days later. CONCLUSIONS: Partial pancreatectomy is an acceptable surgical alternative for incomplete graft thrombosis.

Adult↗
PubMed2001

Hemophilia.

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Hemophilia A↗
PubMed2001

Randomized controlled trial of hand-assisted laparoscopic versus open surgical live donor nephrectomy.

BACKGROUND: Laparoscopic live donor nephrectomy for renal transplantation is being performed in increasing numbers with the goals of broadening organ supply while minimizing pain and duration of convalescence for donors. Relative advantages in terms of recovery provided by laparoscopy over standard open surgery have not been rigorously assessed. We hypothesized that laparoscopic as compared with open surgical live donor nephrectomy provides briefer, less intense, and more complete convalescence. METHODS: Of 105 volunteer, adult, potential living-renal donors interested in the laparoscopic approach, 70 were randomly assigned to undergo either hand-assisted laparoscopic or open surgical live donor nephrectomy at a single referral center. Objective data and subjective recovery information obtained with telephone interviews and validated questionnaires administered 2 weeks, 6 weeks, and 6-12 months postoperatively were compared between the 23 laparoscopic and 27 open surgical patients. RESULTS: There was 47% less analgesic use (P=0.004), 35% shorter hospital stay (P=0.0001), 33% more rapid return to nonstrenuous activity (P=0.006), 23% sooner return to work (P=0.037), and 73% less pain 6 weeks postoperatively (P=0.004) in the laparoscopy group. Laparoscopic patients experienced complete recovery sooner (P=0.032) and had fewer long-term residual effects (P=0.0015). CONCLUSIONS: Laparoscopic donor nephrectomy is associated with a briefer, less intense, and more complete convalescence compared with the open surgical approach.

Activities of Daily Living↗
PubMed2001

Outcome of liver transplantation for hepatitis B: report of a single center's experience.

Results of liver transplantation (LT) for hepatitis B have improved significantly with the use of hepatitis B immune globulin (HBIG) and/or lamivudine. The aim of this study is to review the long-term outcome of patients who underwent LT for hepatitis B. Records of 41 patients who underwent LT for hepatitis B and survived 3 months or longer post-LT were reviewed. Twenty patients were administered no immunoprophylaxis or short-term intramuscular HBIG, whereas 21 patients were administered high-dose intravenous (IV) HBIG. Median post-LT follow-up in these 2 groups was 76 months (range, 4 to 155 months) and 25 months (range, 4 to 68 months), respectively. Hepatitis B recurred in 15 (75%) and 4 patients (19%) who underwent LT in the pre-HBIG and post-HBIG eras, respectively. Cumulative rates of recurrent hepatitis B at 1 and 3 years post-LT in these 2 groups were 66% and 77% and 20% and 20%, respectively (P <.001). Recurrent hepatitis B in the post-HBIG era correlated with antibody to hepatitis B surface antigen titer less than 100 IU/L. Nine patients with recurrent hepatitis B were administered lamivudine for 13 to 49 months (median, 28 months); 6 patients continued to have stable or improved liver disease, whereas 3 patients developed virological breakthrough with slow deterioration of liver disease. Long-term IV HBIG is effective in preventing recurrent hepatitis B. The risk for recurrent hepatitis B is negligible after the first year post-LT. Among patients with no virological breakthrough, lamivudine can stabilize or improve liver disease for up to 4 years in patients with recurrent hepatitis B post-LT.

Adult↗
PubMed2000

Increased impact of acute rejection on chronic allograft failure in recent era.

BACKGROUND: Acute rejection (AR) remains a major risk factor for the development of chronic renal allograft failure (CAF), which is a major cause of late graft loss. With the introduction of several newer immunosuppressive agents (e.g., mycophenolate mofetil, tacrolimus and neoral) acute rejection rates have been steadily decreasing. However, the incidence of CAF has not decreased as dramatically as the incidence of acute rejection. One possible explanation is that the impact of AR on CAF is changing. The goal of this study was to analyze the relative impact of AR era on the development of CAF. METHODS: We evaluated 63,045 primary renal transplant recipients reported to the USRDS from 1988 to 1997. CAF was defined as graft loss after 6 months posttransplantation, censored for death, acute rejection, thrombosis, infection, surgical complications, or recurrent disease. A Cox proportional hazard model correcting for 15 possible confounding factors evaluated the relative impact of AR on CAF. The era effect (years 1988-1989, 1990-1991, 1992-1993, 1994-1995 and 1996-1997) was evaluated by an era versus AR interaction term. RESULTS: An AR episode within the first 6 months after transplantation was the most important risk factor for subsequent CAF (RR=2.4, CI 2.3-2.5). Compared with the reference group (1988-89 with no rejection), having an AR episode in 1988-89, 1990-1991, 1992-1993, 1994-1995, and 1996-1997, conferred a 1.67, 2.35, 3.4, 4.98 and 5.2-fold relative risk for the subsequent development of CAF (P<0.001). CONCLUSIONS: Independently of known confounding variables, the impact of AR on CAF has significantly increased from 1988 to 1997. This effect may in part explain the relative lack of improvements in long term renal allograft survival, despite a decline in AR rates.

Acute Disease↗
PubMed2000

Impact of pre-existing donor hypertension and diabetes mellitus on cadaveric renal transplant outcomes.

Hypertension (HTN) and diabetes mellitus (DM) predispose to systemic atherosclerosis with renal involvement. The prevalence of HTN and DM in cadaveric renal donors (affected donors) and the results of transplantation are unknown. We investigated these issues with national data from the US Renal Data System. A total of 4,035 transplants from affected donors were matched 1:1 with unaffected controls according to donor age and race, recipient race, and year of transplantation. Graft and patient survival were estimated. Among the 25,039 solitary renal transplantations performed between July 1, 1994, and June 30, 1997, cadaveric renal transplants from donors with HTN accounted for 15%, and donors with DM, 2%. Programs with 1-year cadaveric renal graft survival rates greater than 90% had 50% less affected donors compared with programs having 1-year cadaveric renal graft survival rates of 85% or less. Compared with donor-age-matched controls, transplants from affected donors were at minimally increased risk for primary nonfunction, delayed graft function, and acute rejection. Three-year graft survival rates were 71% in affected donor organs and 75% in controls (P = 0.001). Compared with controls, duration of HTN was an independent risk factor for graft survival (3-year graft survival rates, 75% versus 65%; relative risk = 1.36 for HTN >10 years; P < 0.001). A substantial fraction of cadaveric renal donors have preexisting HTN. Programs transplanting fewer affected donor kidneys had better than average results. Because the negative impact of donor HTN and DM on transplant outcome was of moderate degree except when the duration of donor HTN was greater than 10 years, use of affected donors should not be discouraged, but graft and patient survival analyses should account for their presence.

Adolescent↗
PubMed1999

CD2 and CD3 receptor-mediated tolerance: constraints on T cell activation.

BACKGROUND: Antigen specific allograft tolerance is induced in mice by anti-CD2 plus anti-CD3epsilon monoclonal antibody (mAb) treatment. Because anti-CD2 mAb inhibits several aspects of anti-CD3epsilon driven T cell activation, we investigated what components of T cell activation are required or may be dispensed with for tolerance induction. Anti-CD3epsilon-mediated T cell activation depends on FcgammaR interactions. METHODS: To assess the role of FcgammaR-mediated T cell activation in tolerance induction, FcgammaR binding IgG or non-binding IgG3 anti-CD3epsilon mAbs were examined. RESULTS: These mAbs, administered in conjunction with anti-CD2, were equally effective in inducing tolerance. Moreover, in vivo administration of a blocking mAb directed against the FcgammaR, or the use of allograft recipients deficient in FcgammaR, had no effect on tolerance induction. Blocking IL-2 using mAb directed against IL-2 or IL-2R also did not prevent the induction of tolerance. These results suggest that complete T cell activation was not required for tolerance induction. However, substitution of a partially activating mAb, directed against the T cell receptor (TCR) beta subunit for anti-CD3epsilon, failed to synergize with anti-CD2 mAb to induce tolerance. The anti-TCRbeta mAb and anti-CD3epsilon mAb were found to differentially down modulate expression of TCR/CD3 complex subunits. In particular, anti-CD3epsilon caused transient down modulation of the TCRbeta receptor subunit and the TCRzeta signaling module, and this pattern was enhanced and prolonged by anti-CD2. Anti-TCRbeta caused persistent TCRzeta modulation but no TCRbeta modulation, and anti-CD2 did not influence this pattern. CONCLUSIONS: These results suggest that, although full T cell activation is not required for the induction of tolerance by anti-CD2 plus anti-CD3epsilon mAb, a signal transduction pathway that is associated with TCRbeta and TCRzeta expression, and, specifically, is perturbed by mAb binding of the CD3epsilon epitope, is critical.

Animals↗
PubMed1999

Renal transplantation in children with severe lower urinary tract dysfunction.

PURPOSE: Renal transplantation in children with end stage renal disease due to congenital urological malformations has traditionally been associated with a poor outcome compared to transplantation in those with a normal urinary tract. In addition, the optimal urological treatment for such children remains unclear. To address these issues, we retrospectively reviewed our experience with renal transplantation in this population. MATERIALS AND METHODS: Between 1986 and 1998, 12 boys and 6 girls a mean age of 8.4 years with a severe dysfunctional lower urinary tract underwent a total of 15 living related and 6 cadaveric renal transplantations. Urological anomalies included posterior urethral valves in 8 cases, urogenital sinus anomalies in 4, the prune-belly syndrome in 2, and complete bladder duplication, ureterocele, lipomeningocele and the VATER syndrome in 1 each. In 11 children (61%) bladder augmentation or continent urinary diversion was performed, 2 (11%) have an intestinal conduit and 5 (28%) have a transplant into the native bladder. RESULTS: In this group patient and overall allograft survival was 100 and 81%, respectively. These values were the same in all children who underwent renal transplantation at our center during this era. In the 17 children with a functioning transplant mean serum creatinine was 1.4 mg./dl. Technical complications occurred in 4 patients (22%), including transplant ureteral obstruction in 2 as well as intestinal conduit stomal stenosis and Mitrofanoff stomal incontinence. CONCLUSIONS: Renal transplantation may be successfully performed in children with end stage renal disease due to severe lower urinary tract dysfunction. Bladder reconstruction, which may be required in the majority of these cases, appears to be safe when performed before or after the transplant. A multidisciplinary team approach to surgery is advantageous.

Adolescent↗
PubMed1999

Renal transplantation at the University of Michigan 1964 to 1999.

The Michigan Kidney Transplant Program has existed for 35 years. Outcomes have improved dramatically as the one-year survival of cadaver kidney grafts increased from 25% to 85-90%. Patient deaths in the first year are now uncommon. Indications for renal transplantation have been extended to infants, the elderly, diabetics and to patients with other significant health problems who would not have been candidates in the past. Chronic administration of large doses of corticosteroids is no longer necessary and the associated morbidity is largely avoided. Improvements in immunosuppression, especially the introduction of cyclosporine, account for much of this progress. With success has come increasing demand. Unfortunately, the gap between the number of available donor kidneys and the number of patients listed for a cadaver transplant continues to increase rather than diminish. Greater acceptance of volunteer donation, as has occurred in our own program, will help to reduce this shortage. If the past forecasts the future, we can anticipate extraordinary advances during the next 35 years.

Actuarial Analysis↗
PubMed1998

Incidence and management of biliary complications after 291 liver transplants following the introduction of transcystic stenting.

BACKGROUND: Biliary complications occur frequently after liver transplantation, and many are historically related to T tubes. Stents placed through the donor cystic duct have been used to attempt to reduce tube-related complications yet maintain access to the biliary tree. METHODS: The outcomes of all liver transplant procedures performed at the University of Michigan between December 7, 1990 (when transcystic stenting was first used), and April 6, 1995, were analyzed retrospectively. Preoperative, perioperative, and postoperative variables were studied in relationship to biliary complications. The management of complications was also reviewed. RESULTS: A total of 291 transplants qualified for study. The overall biliary complication rate was 25%, with no difference between the 237 patients who received transcystic stents, the 28 who received T tubes, and the 26 who received no tube. Among the complications patients experienced, 65% had stricture(s), 44% had stone or sludge formation, and 40% had a leak. Complications attributable solely to transcystic stents occurred in 4% of cases. Advanced age was the only preoperative variable associated with complications. Primary sclerosing cholangitis was associated with intrahepatic strictures, and prolonged cold ischemia time and rejection were associated with stone or sludge formation. Nonoperative management had the highest success rate for anastomotic stricture (76%) and the lowest for intrahepatic strictures (65%). Only one death was directly attributable to a biliary complication. CONCLUSION: Transcystic stenting reduces the incidence of significant tube-related complications, but not the frequency of other biliary complications. Biliary complications can usually be managed percutaneously or endoscopically, although intrahepatic strictures and large, early leaks frequently require reoperation. Aggressive, early management of these complications can reduce excess mortality to less than 2%.

Adolescent↗
PubMed1998

Tolerance induction by anti-CD2 plus anti-CD3 monoclonal antibodies: evidence for an IL-4 requirement.

Anti-CD2 mAb plus anti-CD3 mAb induce alloantigen specific tolerance. We sought to determine whether Th2 cytokines are involved in the induction of tolerance in this model. Addition of anti-IL-4 mAb or anti-IL-10 mAb to anti-CD2 plus anti-CD3 treatment abrogated tolerance and resulted in graft survivals of 26+/-4 and 25+/-5 days, respectively. Splenocytes from the anti-IL-4 mAb and anti-IL-10 groups had greater proliferation in response to alloantigen than either tolerant or naive groups. Cytokine analysis of MLR supernatants showed increased IL-10 in the tolerant group and increased IFN-gamma in the anti-IL-4 mAb treated group. Donor-specific alloantibody responses in untreated immune animals had a predominantly Th1 (IgG2a) alloantibody response, while the tolerogenic regimen reduced the ratio of IgG2a:IgG1 titers. The addition of anti-IL-4 mAb to the tolerogenic regimen partly restored the Th1-related IgG2a response. Tolerance did not develop in IL-4 knockout animals treated with anti-CD2 plus anti-CD3 (mean graft survival, 27+/-5 days). Restoration of IL-4 to IL-4 knockout animals by gene transfer with plasmid DNA resulted in prolongation of survival to 46+/-7 days, while adoptive transfer of wild-type splenocytes into IL-4 knockout recipients resulted in indefinite graft survival (>60 days) and indefinite survival of second donor-type grafts. IL-10 gene transfer to IL-4 knockout recipients did not prolong graft survival (28+/-4). These results demonstrate that tolerance in this model is mediated at least in part by Th2-type cells that secrete IL-4, promote IL-10 and IgG1 production, and inhibit alloantigen reactivity.

Animals↗