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Biomedical subjects

H A Gritsch

Publications and source records attributed to H A Gritsch.

At least 37 records · Page 2Linked to original sources
PubMed1998

A prospective, randomized trial to compare tacrolimus and prednisone with and without mycophenolate mofetil in patients undergoing renal transplantation: first report.

PURPOSE: Between September 20, 1995 and September 20, 1996, 120 patients were entered into a prospective, randomized trial comparing tacrolimus and prednisone with (61) and without (59) 2 gm. mycophenolate mofetil daily to determine whether mycophenolate mofetil was associated with a lower incidence of rejection. MATERIALS AND METHODS: Mean recipient age plus or minus standard deviation was 50.8+/-14.1 years (range 18.8 to 84.1). Mean donor age was 34.3+/-21.7 years (range 0.01 to 76). Of the donors 18 (15%) were older than 60 years. Mean cold ischemia time was 30.9+/-8.4 hours (range 14.2 to 49). Median followup was 8.6+/-0.5 months. RESULTS: The 6-month actuarial patient survival was 95%, 92% in the double therapy group and 98% in the triple therapy group (not significant). The 6-month actuarial graft survival was 88%, 84% in the double therapy group and 92% in the triple therapy group (not significant). The overall incidence of rejection and steroid resistant rejection was 34.2 and 4.2%, respectively. There was a strong trend toward less rejection in the mycophenolate mofetil group than in the double therapy group (26.2 versus 42.4%). Crossover was common, and was 42.6% from triple to double therapy and 18.6% from double to triple therapy. The reasons for discontinuation of mycophenolate mofetil were gastrointestinal toxicity, primarily diarrhea, or less commonly hematological toxicity, primarily neutropenia or thrombocytopenia. Gastrointestinal toxicity was ameliorated by separating the doses of tacrolimus and mycophenolate mofetil by 2 to 4 hours, and reducing the dose to 1 gm. daily. CONCLUSIONS: Mycophenolate mofetil appears to be a useful third agent with tacrolimus in patients undergoing renal transplantation, and is associated with a reduction in the rate of rejection and a low incidence of steroid resistant rejection. There is a high incidence of gastrointestinal toxicity associated with the 2 gm. daily dose but this complication is relatively straightforward to manage.

Actuarial Analysis↗
PubMed1998

Serum lipase as a marker for pancreatic allograft rejection.

In patients with enteric drainage of pancreas transplants, urinary amylase cannot be used as a marker of rejection. Since most of the patients in our center have enteric drainage, the aim of this study was to evaluate serum lipase as a potential marker for rejection. From July 1994 to March 1997, 100 patients underwent pancreas transplantation with enteric (78) or bladder (22) drainage. Forty-two of the 100 patients had both daily serum lipase (sLip) values and either kidney core or fine needle aspiration biopsies of the pancreas and/or kidney. Thirty-one of the 42 had biopsy proven rejection and were treated on day 0 (D0). From day -7 (D -7) to day +7 (D +7), sLip, serum amylase (sAmy), fasting blood sugar (FBS) and serum creatinine (sCr) were measured daily. Serum lipase values rose from 322 +/- 107 IU/L on D -2 to 634 +/- 247 IU/L on D -1 (p = 0.0203) in 22 of the 31 patients with biopsy proven rejection (sensitivity 71%). The rise in sCr in combined kidney pancreas transplants with biopsy proven rejection was a better marker than sLip (sensitivity 86%). The sensitivity of sAmy and FBS was 50 and 33%, respectively. Other than sCr, sLip appeared to be the best marker for acute rejection in enterically drained pancreas transplants which should be useful as a non-invasive indicator of rejection in solitary pancreas transplants where sCr cannot be used.

Amylases↗
PubMed1998

Reducing the length of stay after kidney transplantation--the intensive outpatient unit.

The need to reduce the costs associated with the initial hospitalization for kidney transplantation has led to the development of outpatient facilities in which patients can be seen on a daily basis. The implementation of a kidney transplant intensive outpatient unit (IOPU) is described. Prior to the opening of the IOPU, the median and mean lengths of stay after kidney transplantation in our program were 14.0 and 18.9 d, respectively. Subsequent to the opening of the IOPU, the median and mean lengths of stay after kidney transplantation have gradually decreased and are currently 5.0 and 7.5 d, respectively. The median inpatient cost of transplantation, excluding organ acquisition charges, has decreased by 54%, from $25516 to $11616. Patient satisfaction has exceeded 80%. The IOPU represents an effective means of reducing the cost associated with transplantation, without sacrificing the quality of care.

Cost Savings↗
PubMed1997

Clinical significance of renal allograft biopsies with "borderline changes," as defined in the Banff Schema.

BACKGROUND: The Banff Schema suggests the term "borderline changes" for biopsies showing changes insufficient for a diagnosis of mild acute rejection. The appropriate clinical management for patients showing such changes on biopsy is controversial. METHODS: We reviewed the clinical course and response to antirejection therapy of 24 patients with borderline changes, and compared our findings with those obtained from 14 patients with mild acute rejection. Patients were classified as showing complete response, partial response, or no response to antirejection treatment, depending on whether the posttreatment fall in serum creatinine was >70%, 30-70%, or <30% of the pretreatment rise, respectively. Renal allograft biopsies were systematically evaluated in accordance with the Banff schema. RESULTS: Complete response to antirejection therapy was seen in 15/24 (63%), partial response in 3/24 (13%), and nonresponse in 6/24 (25%) patients with borderline change. Compared with patients showing complete response, nonresponse was associated with higher scores of acute tubular necrosis and chronic allograft nephropathy (P<0.05). By comparison, 12/14 (86%) cases of mild acute rejection showed complete response to antirejection therapy (P=0.25 vs. patients with borderline change), and lack of response was associated with a higher score for chronic allograft nephropathy. CONCLUSION: When biopsies are done in the context of renal allograft dysfunction, borderline changes frequently require increased immunosuppression. These findings should not be extrapolated to protocol biopsies performed in the setting of stable graft function.

Adult↗
PubMed1997

En bloc pancreas and kidney transplantation in a patient with limited vascular access.

We report a successful en bloc pancreas and kidney transplantation on a type I diabetic patient with advanced peripheral arterial calcific disease, who had frequent life-threatening episodes of hypoglycemia. The en bloc double organ, created by joining the graft renal artery to the arterial Y graft of the pancreas, was implanted to the proximal left common iliac artery, which was the only site available for an arterial anastomosis. Under appropriate circumstances, this procedure would be an option for potential combined pancreas-kidney transplant recipients with severe calcific arterial disease.

Adult↗
PubMed1997

Autologous lymphokine-activated killer cell therapy of Epstein-Barr virus-positive and -negative lymphoproliferative disorders arising in organ transplant recipients.

Lymphoreticular malignancies, collectively called posttransplant lymphoproliferative disorders (PTLD), eventually develop in 2-5% of organ transplant recipients. They frequently undergo regression when immunosuppression is reduced or stopped. This feature has been associated with a previous or de novo Epstein-Barr virus (EBV) infection. We herein describe immunotherapy with autologous lymphokine-activated killer (LAK) cells in seven patients with PTLD (four EBV-positive patients and three EBV-negative patients). Autologous peripheral blood mononuclear cells were obtained by leukapheresis, depleted of monocytes, and cultured in the presence of interleukin 2 for 10 to 11 days. A single dose of 5.2 x 10(9) to 5.6 x 10(10) LAK cells was given intravenously. Systemic interleukin 2 was not administered. The four patients with EBV+ PTLD had complete tumor regression; two of them developed controllable rejection. Three patients are well 13-16 months after treatment; the fourth patient died of pneumonia 41 days after infusion. Three patients with EBV- lymphomas had no response despite prior evidence that their tumors also were subject to immune surveillance. Two of these three patients died after being given other treatment, and the third patient has persistent tumor. In conclusion, autologous LAK cell infusion was effective for treatment of four EBV+ organ transplant recipients. LAK cell efficacy for three patients with EBV- PTLD was not evaluable under the management circumstances in which this treatment was utilized.

Adult↗
PubMed1997

Spontaneous arterioenteric fistula after pancreas transplantation.

Chronic pancreas transplant rejection with enteric exocrine drainage can lead to significant long-term complications. We report a case of a 47-year-old male insulin-dependent diabetic who survived the complications of peripancreatic abscess, enterocutaneous fistula, and arterioenteric fistula related to pancreas transplantation. To avoid these long-term complications, we now recommend elective removal of nonfunctioning, enterically drained pancreas allografts.

Anastomosis, Surgical↗
PubMed1997

Tacrolimus rescue therapy for renal allograft rejection--five-year experience.

Over the 5 year period from 7/14/1989 until 5/24/1994, we have attempted graft salvage with tacrolimus conversion in a total of 169 patients (median age 33 years, range 2-75 years) with ongoing rejection on baseline CsA immunosuppression after failure of high dose corticosteroids and/or antilymphocyte preparations to reverse rejection. The indications for conversion to tacrolimus were ongoing, biopsy confirmed rejection in all patients. The median interval to tacrolimus conversion was 2 months (range 2 days to 55 months; mean 4.3+/-2.6 months) after transplantation. All patients had failed high dose corticosteroid therapy and 144 (85%) of the 169 patients had received at least one course of an antilymphocyte preparation plus high dose corticosteroid therapy prior to conversion. Twenty-eight patients (17%) were dialysis-dependent at the time of conversion owing to the severity of rejection. With a mean follow-up of 30.0+/-2.4 months (median 36.5 months, range 12-62 months), 125 of 169 patients (74%) have been successfully rescued and still have functioning grafts with a mean serum creatinine (SCR) of 2.3+/-1.1 mg/dl. Of the 144 patients previously treated with antilymphocyte preparations, 117 (81%) were salvaged. Of the 28 patients on dialysis at the time of conversion to tacrolimus, 13 (46%) continue to have functioning grafts (mean SCR 2.15+/-0.37 mg/dl) at a mean follow-up of 37.3+/-16.7 months. In the 125 patients salvaged, prednisone doses have been lowered from 28.0+/-9.0 mg/d (median 32, range 4-60 mg/d) preconversion to 8.5+/-4.1 mg/d (median 12 mg/d, range 2.5-20 mg/d) postconversion. Twenty-eight patients (22.4%) are currently receiving no steroids. This 5 year experience demonstrates that tacrolimus has sustained efficacy as a rescue agent for ongoing renal allograft rejection. Based on these data, we recommend that tacrolimus be used as an alternative to the conventional drugs used for antirejection therapy in renal transplantation.

Adolescent↗
PubMed1997

Acute renal allograft rejection in patients with Epstein-Barr virus associated post-transplant lymphoproliferative disorder.

BACKGROUND: There is a reciprocal relationship between post-transplant lymphoproliferative disorder (PTLD) and rejection: aggressive treatment of rejection can result in PTLD, while treatment of PTLD by reducing immunosuppression can result in recrudescence of rejection. The literature on the relationship between PTLD and rejection episodes is limited. METHODS: The clinical course and outcome of rejection episodes occurring prior to and following a diagnosis of PTLD were studied in 20 renal transplant recipients. RESULTS: The diagnosis of PTLD was preceded by rejection in 12/20 (60%) patients. OKT3 treatment was associated with early onset PTLD, which involved the allograft in 6/7 patients (86%). The risk of rejection following reduced immunosuppression was 7/14 (50%). Post-PTLD rejection left untreated led to graft loss in 3 patients. The remaining 4 patients responded satisfactorily to anti-rejection therapy. CONCLUSIONS: Reduction of immunosuppression for PTLD is frequently, but not invariably, complicated by rejection. The clinical outcome of PTLD does not correlate with the occurrence or reversibility of rejection episodes.

Adult↗
PubMed1996

Tacrolimus in pediatric renal transplantation.

Tacrolimus was used as the primary immunosuppressive agent in 69 pediatric renal transplantations between December 17, 1989, and June 30, 1995. Children undergoing concomitant or prior liver and/or intestinal transplantation were excluded from analysis. The mean recipient age was 10.3+/-5.0 years (range, 0.7-17.5 years). Seventeen (24.6%) children were undergoing retransplantation, and six (8.7%) had a panel reactive antibody level of 40% or higher. Thirty-nine (57%) cases were with cadaveric kidneys, and 30 (43%) were with living donors. The mean donor age was 28.0+/-14.7 years (range, 1.0-50.0 years), and the mean cold ischemia time for the cadaveric kidneys was 27.0+/-9.4 hr. The antigen match was 2.7+/-1.2, and the mismatch was 3.1+/-1.2. All patients received tacrolimus and steroids, without antibody induction, and 26% received azathioprine as well. The mean follow-up was 32+/-20 months. One- and 4-year actuarial patient survival rates were 100% and 95%. One- and 4-year actuarial graft survival rates were 99% and 85%. The mean serum creatinine level was 1.2+/-0.8 mg/dl, and the calculated creatinine clearance was 82+/-26 ml/min/1.73 m2. The mean tacrolimus dose was 0.22+/-0.14 mg/ kg/day, and the level was 9.5+/-4.8 ng/ml. The mean prednisone dose was 2.1+/-4.9 mg/day (0.07+/-0.17 mg/kg/day), and 73% of successfully transplanted children were off prednisone. Seventy-nine percent were not taking any antihypertensive medications. The mean serum cholesterol level was 158+/-54 mg/dl. The incidence of delayed graft function was 4.3%. The incidence of rejection was 49%, and the incidence of steroid-resistant rejection was 6%. The incidence of rejection decreased to 27% in the most recent 26 cases (January 1994 through June 1995). The incidence of new-onset diabetes was 10.1%; six of the seven affected children were able to be weaned off insulin. The incidence of cytomegalovirus disease was 13%, and that of posttransplant lymphoproliferative disorder was 10%; the incidence of posttransplant lymphoproliferative disorder in the last 40 transplants was 5% (two cases). All of the children who developed posttransplant lymphoproliferative disorder are alive and have functioning allografts. Based on this data, we believe that tacrolimus is a superior immunosuppressive agent in pediatric renal transplant patients, with excellent short- and medium-term patient and graft survival, an ability to withdraw steroids in the majority of patients, and, with more experience, a decreasing rate of rejection and viral complications.

Adolescent↗
PubMed1996

Graft hyporeactivity induced by donor-specific bone marrow.

Much interest has recently focused on administration of donor cells with organ transplantation to improve graft outcome. However, whether donor cell administration actually confers donor-specific (DS) hyporeactivity is unknown. The intra-graft events after DS bone marrow (BM) infusion were therefore examined in an in vivo sponge matrix allograft model. Recipient C57BL/6J (B6,H2b) mice (five per group) received either media alone, 10(7) syngeneic (B6), or allogeneic (DBA/2J,H2d) BM cells intravenously. Seven days later, a sponge matrix allograft containing 10(7) allogeneic (DBA) splenocytes was implanted. On various days after grafting, graft-infiltrating cells were tested for in vitro cytotoxicity by 51Cr release assay. Previous DSBM infusion significantly reduced intragraft allospecific cytolytic T-cell (CTL) activity compared with mice receiving syngeneic BM or media alone (3.5 +/- 5.1% vs. 46.2 +/- 13.3% and 47.9 +/- 13.5% at 100:1 E:T, respectively, P < 0.001). Time course studies showed that DSBM impaired allospecific CTL activity whether given on day -10 (3.3% at 100:1 E:T), day -7 (2.2%), day -2(7.7%), or day 0 (6.5%), but was not as effective when given on day +7 (27.1%). Flow cytometry of graft-infiltrating cells on day +12 showed a decreased percentage of CD8+ cells after DSBM, compared with syngeneic BM or media alone (13.1% vs. 38.0% and 36% respectively, P = 0.01), but the percentage of CD4+ cells was similar in all groups (5.5%, 6.9%, and 4%, respectively). Thus, (1) DSBM inhibits allospecific CTL development in the allograft, (2) decreased intra-graft CTL activity after DSBM correlates with a decreased percentage of intragraft CD8+ cells, and (3) DSBM induces hyporeactivity up until the day of the allograft placement, but not thereafter. DSBM may, thus, induce graft hyporeactivity by impairing intragraft immune activation.

Animals↗
PubMed1996

"Suboptimal" kidney donors: the experience with tacrolimus-based immunosuppression.

Female, pediatric, and older donors have been associated with inferior graft survival after renal transplantation. We analyzed these three subgroups in 397 patients receiving tacrolimus-based immunosuppression. There were no differences in recipient age, incidence of retransplantation, or percentage of sensitized patients. Female donors, compared with male donors, were associated with comparable 1- and 3-year patient survival rates (96% and 93% vs. 95% and 92%, respectively) and comparable 1- and 3-year graft survival rates (90% and 80% vs. 88% and 81%, respectively). Renal function was also similar. Recipients of pediatric en bloc kidneys, when compared with recipients of other cadaveric kidneys, also had comparable 1- and 3-year patient survival rates (94% and 94% vs. 95% and 91%, respectively) and comparable 1- and 3-year graft survival rates (84% and 84% vs. 89% and 79%, respectively). Renal function was better in recipients of en bloc kidneys, with a mean serum creatinine level of 1.4+/-1.8 mg/dl vs. 2.0+/-1.5 mg/dl (P=0.01). In contrast to the first two subgroups, donors over 60 years of age, when compared with donors under 60 years of age, were associated with worse 1- and 3-year patient survival rates (88% and 80% vs. 96% and 94%, respectively; P<0.03) and worse 1- and 3-year graft survival rates (74% and 62% vs. 91% and 83%, respectively; P<0.0001). Renal function was worse in the older donor group, with a serum creatinine level of 2.7+/-1.2 mg/ml vs. 1.9+/-1.5 mg/dl (P=0.01). We conclude that, under tacrolimus-based immunosuppression, kidneys from female or very young pediatric donors are not associated with adverse outcomes, whereas kidneys from donors over 60 years of age are associated with inferior outcomes.

Adult↗
PubMed1996

The use of tacrolimus in renal transplantation.

Tacrolimus (FK 506) is a novel immunosuppressive agent that has been in clinical use for solid organ transplantation since 1989. Early clinical trials of tacrolimus in liver, heart, kidney, lung, and intestinal transplantation at the University of Pittsburgh have demonstrated it to be a safe and effective agent with several potential advantages over existing immunosuppressive drugs. More recently, phase I and II multicenter trials of tacrolimus for renal transplantation have been performed; however, data are not yet available from these trials. Our experience with this drug has demonstrated excellent 1- and 2-year actuarial graft survival rates of 89% and 83%, respectively, in adult renal transplantation and 1- and 3-year graft survival rates of 98% and 85%, respectively in pediatric renal transplantation. A major advantage of tacrolimus noted in these trials was the ability to discontinue steroid therapy in approximately 50% of the patients. Tacrolimus has also shown efficacy as a rescue agent for renal allograft rejection failing conventional therapy in 74% of cases. This paper expands on these observations and focuses on the experience we have gained with the use of tacrolimus at our institution over the last 6 years.

Graft Survival↗