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PubMed2000

Fluconazole vs low-dose amphotericin B for the prevention of fungal infections in patients undergoing bone marrow transplantation: a study of the North American Marrow Transplant Group.

Systemic fungal infections are a major problem in bone marrow transplant recipients who have prolonged neutropenia or who receive high-dose corticosteroids. Prophylaxis with Fluconazole or low-dose amphotericin B reduces, but does not eliminate these infections. To determine which prophylactic agent is better, we performed a prospective randomized study. Patients undergoing allogeneic (related or unrelated) or autologous marrow or peripheral stem cell transplantation were randomized to receive Fluconazole (400 mg/day p. o. or i.v.) or amphotericin B (0.2 mg/kg/day i.v.) beginning 1 day prior to stem cell transplantation and continuing until recovery of neutrophils to >500/microl. Patients were removed from their study drug for drug-associated toxicity, invasive fungal infection or suspected fungal infection (defined as the presence of fever >38 degrees C without positive culture while on broad-spectrum anti-bacterial antibiotics). Proven or suspected fungal infections were treated with high-dose amphotericin B (0.5-0.7 mg/kg/day). Patients were randomized at each institution and stratified for the type of transplant. The primary end-point of the study was prevention of documented fungal infection; secondary endpoints included fungal colonization, drug toxicity, duration of hospitalization, duration of fever, duration of neutropenia, duration and total dose of high-dose amphotericin B and overall survival to hospital discharge. From July 1992 to October 1994, a total of 355 patients entered into the trial with 159 patients randomized to amphotericin B and 196 to Fluconazole. Patient groups were comparable for diagnosis, age, sex, prior antibiotic or antifungal therapy, use of corticosteroids prior to transplantation and total duration of neutropenia. Amphotericin B was significantly more toxic than Fluconazole especially in related allogeneic transplantation where 19% of patients developed toxicity vs 0% of Fluconazole recipients (p < 0.05). Approximately 44% of all patients were removed from prophylaxis for presumed fungal infection. Proven fungal infections occurred in 4.1% and 7.5% of Fluconazole and amphotericin-treated patients, respectively. Proven fungal infections occurred in 9.1% and 14.3% of related allogeneic marrow recipients receiving Fluconazole or amphotericin B, respectively, and 2.1% and 5.6% of autologous marrow recipients receiving Fluconazole or amphotericin B, respectively (P > 0.05). In this prospective trial, low-dose amphotericin B prophylaxis was as effective as Fluconazole prophylaxis, but Fluconazole was significantly better tolerated.

Adult↗
PubMed2003

Salvage chemotherapy for refractory or relapsed post-transplant lymphoproliferative disorder in patients after solid organ transplantation with a combination of carboplatin and etoposide.

This pilot study assessed the feasibility and efficacy of salvage chemotherapy (carboplatin and etoposide; CE) supported by granulocyte colony-stimulating factor (GCSF) in patients with refractory or relapsed post-transplant lymphoproliferative disorder (PTLD) following solid organ transplantation. Intensified salvage regimens were not feasible for these patients, due to their immunosuppressive conditions and potential organ (especially kidney and bone marrow) malfunctions. Salvage chemotherapy consisted of carboplatin [area under the curve (AUC) 4], on day 1, etoposide (120 mg/m2), on days 1-3 and GCSF (5 microg/kg) starting on day 5. This therapeutic regimen was planned to be repeated every 21 d. Nine patients (seven with refractory, two with relapsed disease) were enrolled. Five patients were heart transplant recipients, three liver transplant recipients and one patient had been a double lung transplant recipient. Five patients achieved a complete remission (CR), with follow-up at 92, 39, 55+, 17 and 9+ months. One patient showed stable disease after two cycles of CE and one patient had progressive disease. Two patients experienced early deaths, after the first and third cycles of chemotherapy respectively. One died of septic complications and one because of a perforated intestine, which had been infiltrated by lymphoma. In respect of the difficulties experienced in treating patients with refractory or relapsed PTLD after solid organ transplantation, the combination of carboplatin and etopoide with GCSF support (filgrastim) proved to be an effective regimen.

Adult↗
PubMed2004

Hodgkin's lymphoma after post-transplant lymphoproliferative disease in a renal transplant recipient.

Lymphoid malignancies such as post-transplant lymphoproliferative disease (PTLD) are a major complication of solid organ transplantation. Hodgkin's lymphoma (HL) is not part of the typical spectrum of PTLD, but has rarely been reported as a separate complication. We report a case of HL occurring after previous PTLD in a renal transplant recipient. A 9-yr-old girl with end-stage autosomal recessive polycystic kidney disease received a cadaveric renal transplant at 1 yr of age. She developed polymorphic PTLD localized to the bone marrow at 6 yr post-transplant. She was treated with reduction of immunosuppression and alpha-interferon. No chemotherapy or anti-B cell antibody was administered. The PTLD resolved and kidney graft function remained stable. At 9 yr post-transplant, she presented again with fever of 2 wk duration, associated with enlarged lymph nodes at multiple sites. A lymph node biopsy revealed the presence of classic Reed Sternberg cells positive for CD15, CD30 and EB RNA. She was treated with standard combination chemotherapy for HL with COPP/ABV. All immunosuppressive agents were discontinued except for low dose prednisone. The patient had an excellent response, with resolution of her lymphadenopathy and maintenance of stable graft function. RS like cells have been reported in the setting of PTLD, but these cells possess an activated B cell phenotype, are EBV negative and CD15 negative. True HL following PTLD has been reported in only three previous cases, with good response to standard chemotherapy in each.

Epstein-Barr Virus Infections↗
PubMed2004

Interstitial alterations in renal cortex in acute tubular necrosis (ATN) post-renal transplantation and in patients with ATN not related to renal transplant.

BACKGROUND: Abnormalities of renal function with long-term implications can persist after acute tubular necrosis (ATN), probably because of permanent loss of nephrons. Residual areas of fibrosis are also observed in the renal cortex post-ATN. In this study, we investigate the interstitial alterations post-ATN using histological and immunohistochemical methods. METHODS: We studied 11 patients with ATN of different etiologies and 19 patients with ATN post-renal transplantation. Eleven patients with ATN post-renal transplantation and one with ATN not related to renal transplantation were submitted to more than one biopsy because of delayed renal function recovery. The immunohistochemical studies were performed using alpha-smooth muscle-actin (alpha-SM-actin), endothelin, nuclear factor-kappaB (NF-kappaB), Jun-N-terminal kinase (p-JNK) and fibronectin antibodies. We also analyzed the urinary content of transforming growth factor-beta (TGF-beta) during the acute phase of ATN. RESULTS: The immunohistochemical studies showed increased alpha-SM-actin, fibronectin, endothelin, p-JNK and NF-kappaB staining in the tubulointerstitium area from the renal cortex of all patients when compared with controls (p < 0.001), and these increase persisted in the patients submitted to sequential biopsies. One of the patients with ATN without renal transplant and six patients with ATN post-renal transplant developed chronic renal failure. There was a significant increase of TGF-beta excretion in the urine of patients with acute renal failure (p < 0.01) compared with control. CONCLUSIONS: Our data show that the enhancement of renal TGF-beta production and the persistent increase of myofibroblasts, fibronectin, endothelin, p-JNK and NF-kappaB in renal cortex tubulointerstitium post-ATN may explain the impaired recovery of renal function observed in patients post-ATN frequently observed in patients with ATN post-renal transplant.

Actins↗
PubMed1999

High and low pulmonary vascular resistance in heart transplant candidates. A 5-year follow-up after heart transplantation shows continuous reduction in resistance and no difference in complication rate.

BACKGROUND: In heart transplantation candidates, high pulmonary vascular resistance has been found to decrease promptly after heart transplantation without any further reduction during follow-up. Pulmonary hypertension has been described as associated with an increased peri- and postoperative complication rate and mortality. This study describes the evolution of pulmonary vascular resistance and the outcome for patients during 5 years following heart transplantation. METHODS AND RESULTS: Haemodynamic data, complication rate and mortality have been analysed during 5-year follow-up in all patients (n = 80) who were heart transplanted at Sahlgrenska University Hospital from 1988 through 1990. We found a significant and continuous reduction in pulmonary vascular resistance both in patients with a pre-operative high (> 3 Wood Units; n = 36), but reversible on nitroprusside, and pre-operative low (< or = 3 Wood Units; n = 44) pulmonary vascular resistance. A multivariate analysis showed that a pre-operative high mean pulmonary artery and low mean pulmonary capillary wedge pressure predicted the decline in pulmonary vascular resistance during 5 years after heart transplantation. The need for a postoperative assist device, complication rate, and early and late mortality were independent of the pre-operative level of pulmonary vascular resistance. CONCLUSIONS: A continuous reduction in pulmonary vascular resistance during 5 years following heart transplantation was found in patients with both high, but reversible, and low pre-operative resistance levels. The outcome and survival were independent of the pre-operative pulmonary vascular resistance level.

Adolescent↗
PubMed1997

Transmission of hepatitis B by transplantation of livers from donors positive for antibody to hepatitis B core antigen. The National Institute of Diabetes and Digestive and Kidney Diseases Liver Transplantation Database.

BACKGROUND & AIMS: Organ donors are a potential source of transmissible disease after transplantation. The aim of this study was to evaluate the risk of acquiring hepatitis B among transplantation recipients of livers from donors without serum hepatitis B surface antigen (HBsAg) but with antibody to hepatitis B core antigen (anti-HBc). METHODS: The transplantation experience of four centers between 1989 and 1994 was reviewed. Recipients of livers from 674 donors were considered informative for hepatitis B virus transmission. RESULTS: Hepatitis B developed in 18 of 23 recipients of livers from anti-HBc-positive donors (78%) compared with only 3 of 651 recipients of anti-HBc-negative donor livers (0.5%) (P < 0.0001). HBsAg persisted in all recipients with donor-related hepatitis B. Liver histology showed chronic hepatitis of moderate severity in 2 of 13 recipients at 1 year and 5 of 8 recipients between 1.6 and 4.5 years from transplantation. Liver transplantation from an anti-HBc-positive donor was associated with decreased 4-year survival (adjusted mortality hazard ratio of 2.4; 95% confidence interval, 1.4-4.0). CONCLUSIONS: De novo posttransplantation hepatitis B infection occurs at a high rate in recipients of donors with anti-HBc. Transmission of hepatitis B through transplantation suggests that the virus may persist in the liver despite serological resolution of infection.

Hepatitis B↗
PubMed1996

Heart transplantation in patients with diabetic end-organ damage before transplantation.

Diabetes mellitus with preexisting end-organ damage (EOD) is considered a contraindication for heart transplantation. The outcome of such patients has not been well characterized. Among 138 patients transplanted between 12/88 and 7/94, 29 were diabetic (11 insulin-dependent); of these, 12 had preexisting EOD, defined as a creatinine clearance < or = 50 ml/min, a 24-hour urine protein concentration > or = 500 mg/L or typical symptoms of peripheral or autonomic polyneuropathy, and 17 had no EOD. We compared diabetics with and without EOD and non-diabetics (n = 109) for operative mortality, length of stay, serum creatinine, fasting glucose levels, and postoperative prednisone doses at 1,6, and 12 months. Actuarial survival and freedom from rejection and infection were analyzed. Both diabetic groups were significantly older than nondiabetics, Ischemic time, operative mortality, surgical technique, ICU- and total length of stay were similar. Actuarial survival and freedom from rejection were similar among the three groups. Infection rates including CMV did not differ. Serum creatinine levels increased in all groups compared to pretransplant levels (p = 0.001), but without significant differences among the groups. Post-transplant glucose levels at 6 and 12 months were higher for diabetic patients with EOD than for those without or for nondiabetics (183, 153, and 94 mg/dl at 6 months, p = 0.01; 202, 161, and 102 mg/dl at 12 months, p = 0.0001). Prednisone dosage was lower in diabetics with EOD at 6 months, but did not differ among the three groups at 12 months. The incidence of angiographically proven transplant vasculopathy did not differ at 1 and 2 years. Diabetics with preexisting EOD undergoing heart transplantation experience similar short- and intermediate-term results when compared to diabetics without EOD and nondiabetics. Metabolic control is more difficult to achieve, as indicated by higher fasting glucose levels. Larger and longer-term prospective studies have to confirm our findings, since the shortage of donor organs would increase if such patients were transplanted routinely.

Actuarial Analysis↗
PubMed1990

Results of single-lung transplantation for bilateral pulmonary fibrosis. The Toronto Lung Transplant Group.

Between November 1983 and August 1989, we performed single-lung transplantation for end-stage pulmonary fibrosis in 20 patients. Nine patients (45 percent) who survived for more than one year form the basis of this report. Before surgery, the nine survivors had severe restrictive lung disease, with a mean (+/- SD) vital capacity (VC) of 43 +/- 9 percent, a forced expiratory volume in one second (FEV1) of 50 +/- 9 percent, and a single-breath diffusing capacity (DLCO) of 36 +/- 9 percent of predicted values. One year after transplantation, the patients' VC had reached 69 +/- 10 percent, FEV1 79 +/- 15 percent, and DLCO 62 +/- 16 percent of predicted values. Relative perfusion to the transplanted lung rose from 63 +/- 14 percent (three days after surgery) to 77 +/- 7 percent within three months and stayed constant or increased slightly thereafter. Before surgery, despite supplemental oxygen at flow rates varying from 1 to 9 liters per minute, none of the patients could exercise beyond stage 1/2 (2.7 km [1.7 miles] per hour, 5 percent grade) on a modified Bruce treadmill-exercise protocol. All eight patients tested one year or more after transplantation achieved at least stage 1 (2.7 km [1.7 miles] per hour, 10 percent grade), and usually a higher stage, without supplemental oxygen. Arterial oxygen tension returned to normal values in most patients (87 +/- 13 mm Hg), and supplemental oxygen, which all patients required before surgery, was no longer needed by any patient after transplantation. We conclude that in carefully selected patients with end-stage pulmonary fibrosis, single-lung transplantation is an effective treatment.

Adolescent↗
PubMed1996

Exposure to cytomegalovirus from the donated organ is a risk factor for bacteremia in orthotopic liver transplant recipients. Boston Center for Liver Transplantation CMVIG Study Group.

To define predictors of bacteremia and to assess the potential role of exposure to cytomegalovirus (CMV) as a risk factor for bacteremia in liver transplant recipients, an intention-to-treat analysis of data for 146 orthotopic liver transplant recipients who participated in a multicenter, randomized, intervention trial was undertaken. Fifty-eight episodes of bacteremia occurred in 40 (27.4%) of 146 patients within 1 year after transplantation. Bacteremia was diagnosed a median of 39.5 days (range, 1-325 days) after transplantation. One-year mortality rates were higher among patients with bacteremia than among those without bacteremia (47.5% [19 of 40] vs. 18% [19 of 106], respectively; P = .001). A time-dependent multivariate analysis of variables that were significantly (P < or = .05) associated with bacteremia in the univariate analysis showed that donor CMV seropositivity (relative risk [RR], 3.4; 95% confidence interval [CI], 1.6-6.6; P = .0005), age of younger than 16 years (RR, 2.6; 95% CI, 1.3-5.2; P < .0059), and a major abdominal operation after transplantation excluding retransplantation (RR, 3.8; 95% CI, 1.8-8.0; P = .0004) were independently associated with bacteremia. These epidemiologic data suggest that exposure to CMV from the donated organ is an independent risk factor for bacteremia in orthotopic liver transplant recipients.

Bacteremia↗
PubMed2004

Neuropsychological performance after kidney transplantation: a comparison between transplant types and in relation to dialysis and normative data.

BACKGROUND: Neuropsychological (NP) performance after kidney transplantation (TX) has received little attention. This study compared NP functioning between dialysis and transplant patients and between living-related donor (LRD) and cadaver (CAD) transplant recipients. The association between immunosuppressive medication and NP outcomes was also examined. METHODS: One hundred and seventeen transplant recipients (25 LRD and 92 CAD patients) and 145 dialysis patients (77 haemodialysis and 68 peritoneal dialysis) were administered an NP test battery to assess learning and verbal recall, attention and concentration, and psychomotor abilities/speed. Biochemical markers of renal function were also assessed. RESULTS: Overall, transplant patients showed normal cognitive functioning in all domains assessed. NP performance was found to be equivalent in both transplant groups and in patients on cyclosporin and those on tacrolimus. ANCOVAs showed that TX patients performed significantly better than dialysis patients on selective NP tests, i.e. the two memory tasks and two out of the four tests of attention. No differences were found in motor tasks. CONCLUSIONS: Our results reveal no evidence of NP deficits in TX patients. The NP advantage of TX relative to dialysis is evident mainly in verbal memory.

Adult↗
PubMed2006

Long-term cardiovascular risk in transplantation--insights from the use of everolimus in heart transplantation.

Everolimus is a potent immunosuppressive agent that has anti-proliferative activity. The benefits of everolimus vs azathioprine in de novo heart transplant recipients were assessed in a randomized, double-blind study. Patients (n = 634) were randomized to receive everolimus (1.5 mg/day or 3.0 mg/day) or azathioprine; all patients received steroids and full-dose ciclosporin (CsA). The primary endpoint was the incidence of efficacy failure [biopsy-proven acute rejection (BPAR), graft loss, death or loss to follow-up]. The incidence of cardiac allograft vasculopathy (CAV) was assessed by intravascular ultrasound. The incidence and hospitalization costs of major adverse cardiac events (MACE) were assessed after 4 years. The incidence of efficacy failure was significantly reduced with everolimus compared with azathioprine at 12, 24 and 48 months (P < 0.05), largely because of a lower incidence of BPAR. An increase in serum creatinine levels was seen with everolimus compared with azathioprine, likely attributed to CsA nephrotoxicity. There was a significantly larger increase in vascular intimal thickness with azathioprine than with everolimus (P <or= 0.01), which was accompanied by a significantly lower incidence of CAV in the everolimus groups. After 4 years, the incidence of MACE was higher with azathioprine than with either dose of everolimus. MACE-related treatment costs were estimated at 431,428 dollars for azathioprine, 136,664 dollars for everolimus 1.5 mg/day (68% saving) and 191,957 dollars for everolimus 3.0 mg/day (56% saving). Everolimus is significantly more effective than azathioprine in preventing efficacy failure in de novo heart transplant recipients and is also associated with reduced incidence and severity of CAV and MACE at 4 years post-transplant. The reduced 4-year incidence of MACE is likely to lead to substantially reduced hospitalization costs. Since cardiovascular morbidity and mortality are important factors in the long-term survival of renal transplant recipients, applying lessons from the use of everolimus in heart transplantation may further improve the understanding of managing cardiovascular risk in renal transplantation.

Azathioprine↗
PubMed1997

Management of the cardiac transplant recipient: roles of the transplant cardiologist and primary care physician.

Cardiac transplantation has become an accepted treatment for selected patients with end-stage heart failure. Despite a successful transplant, denervated transplanted hearts respond differently to cardiac drugs than nontransplanted hearts. The treatments for bradycardia, tachycardia, and hypotension are different than for nontransplanted hearts. Despite the improvement in long-term survival, a number of complications may occur posttransplantation. These complications include, allograft rejection, infection, allograft coronary artery disease, and malignancy. Additionally, posttransplant patients may have complications from the immunosuppressive agents cyclosporine, prednisione, and azathioprine. Such complications include drug interactions with commonly prescribed medications, hypertension, hyperlipidemia, osteoporosis, and gastrointestinal complications. The purpose of this article is to discuss the management of the cardiac transplant recipient as it relates to the aforementioned complications. Management of the cardiac transplantation patient by the primary care physician will also be discussed, including indications for consultation by the primary care physician with the transplant center.

Bradycardia↗
PubMed1992

An appraisal of pediatric liver transplantation from living relatives. Initial clinical experiences in 20 pediatric liver transplantations from living relatives as donors.

The authors performed 20 liver transplantations from living related donors between June 1990 and July 1991. The 20 pediatric patients (14 biliary atresia, two Budd-Chiari syndrome, one liver cirrhosis after hepatitis C viral infection (HCV hepatitis), 1 progressive intrahepatic cholestasis, 1 liver cirrhosis, 1 protoporphyria) were transplanted with 11 left lobes, eight left lateral segments, and one right lobe. The choice of donors was restricted to the parents of the recipients. The immunosuppressive treatment consisted of FK 506 and steroids. Seventeen recipients are alive, 15 of whom are well and at home. Two recipients, who underwent emergency transplantation, died of postoperative complications. Another recipient died of accidental asphyxia at 6 months after the transplantation. All 20 donors had uneventful postoperative courses and were able to resume their normal social lives. The arterial ketone body ratio (AKBR) increased to above 1.0 within 2 days after the transplantation in all cases. Relatively mild rejection episodes were encountered in only two cases transplanted with ABO-compatible grafts, and these were treated successfully with steroids and FK 506.

Adolescent↗
PubMed2000

Cell death in human lung transplantation: apoptosis induction in human lungs during ischemia and after transplantation.

OBJECTIVE: To examine the presence and extent of apoptosis as well as the affected cell types in human lung tissue before, during, and after transplantation. SUMMARY BACKGROUND DATA: Apoptosis has been described in various human and animal models of ischemia-reperfusion injury, including heart, liver, and kidney, but not in lungs. Therefore, the presence of apoptosis and its role in human lungs after transplantation is not clear. METHODS: Lung tissue biopsies were obtained from 20 consecutive human lungs for transplantation after cold ischemic preservation (1-5 hours), after warm ischemia time (during implantation), and 30, 60, and 120 minutes after graft reperfusion. To detect and quantify apoptosis, fluorescent in situ end labeling of DNA fragments (TUNEL assay) was used. Electron microscopy was performed to verify the morphologic changes consistent with apoptosis and to identify the cell types, which were lost by apoptosis. RESULTS: Almost no evidence of apoptosis was found in specimens after immediate cold and warm ischemic periods. Significant increases in the numbers of cells undergoing apoptosis were observed after graft reperfusion in a time-dependent manner. The mean fraction of apoptotic cells at 30, 60, and 120 minutes after graft reperfusion were 16.6%, 22.1%, and 34.9% of total cells, respectively. Most of the apoptotic cells appeared to be alveolar type II pneumocytes, as confirmed by electron microscopy. CONCLUSIONS: Programmed cell death (apoptosis) appears to be a significant type of cell loss in human lungs after transplantation, and this may contribute to ischemia-reperfusion injury during the early phase of graft reperfusion. This cell loss might be responsible for severe organ dysfunction, which is seen in 20% of patients after lung transplantation. Therefore, this work is of importance to surgeons for the future development of interventions to prevent cell death in transplantation.

Adolescent↗
PubMed2002

Selecting patients for heart transplantation: which patients are too well for transplant?

In the context of contemporary medical and surgical therapy, the revolutionary procedure of cardiac transplantation should be redefined in its relative role. Based on the assumption that its goal is to prolong life while improving its quality, and in the absence of randomized clinical trial data testing its benefit, data from early breakthrough studies, more recent observational cohort studies, and studies testing other therapies in advanced heart failure must be analyzed to characterize clinical profiles of patients who should be considered too well for cardiac transplantation at specific stages of their disease processes. These profiles likely include advanced heart failure with (1) low risk according to the Heart Failure Survival Score, (2) peak oxygen consumption greater than 14 to 18 mL/kg/min without other indications, (3) left ventricular ejection fraction less than 20% alone, (4) history of New York Heart Association class III to IV symptoms alone, (5) history of ventricular arrhythmias alone, (6) no previous attempt at comprehensive neurohormonal blockade, and (7) no structured cardiac transplantation evaluation in a designated cardiac transplantation center. The evaluation may identify the potential transplant candidate, who could be placed on a national potential transplant candidate list, combining the psychologic benefit of acceptance by the program with an ongoing openness to the diversity of advanced heart failure treatment modalities.

Female↗
PubMed1980

Effect of blood transfusions on renal transplantation: study of 191 consecutive first transplants from living related donors.

One hundred ninety-one consecutive living related transplants performed from 1969 to the end of 1978 have been analyzed for the effect of pretransplant blood transfusions. Superior graft survival was observed in transfused patients transplanted with a one HLA haplotype-disparate kidney, whereas no effect of blood transfusions could be observed on the survival of HLA-identical transplants. The frequency of first rejection episodes was significantly reduced in transfused compared to nontransfused one haplotype-mismatched transplants, while no influence of blood transfusions was seen in patients with HLA-identical transplants. The survival of patients was, however, not influenced by previous transfusions. Pretransplant hemodialysis improved graft survival and patient survival; the difference was, however, only significant at 2 years in the one haplotype-mismatched group. When analyzed separately, both blood transfusions and hemodialysis had a beneficial effect on graft survival in one haplotype-mismatched transplants.

Adult↗
PubMed1992

Pancreatic islet blood flow after syngeneic pancreaticoduodenal transplantation in rats. Differences between the blood perfusion of the native and the transplanted gland.

Inbred male Sprague-Dawley rats were transplanted with syngeneic pancreaticoduodenal grafts. Diabetes was induced in some of the recipient animals by an i.v. injection of streptozotocin one week before transplantation, while the remaining control rats were untreated, and thus had both an intact native and a transplanted pancreas. The left kidney of the recipient was removed and its blood vessels were used for the graft vascular anastomosis. The graft duodenum was sutured end-to-side to the ileum of the recipient. Two weeks after transplantation the rates of blood flow through both the native and transplanted pancreas and duodenum were measured. The blood perfusion of the whole pancreas and the islets was higher in the tx than in the native gland, although no difference was seen with regard to the duodenum. Administration of glucose to control animals had no effect on either native or tx whole pancreatic or intestinal blood flow. However, the islet blood flow through the native pancreas was increased in response to glucose, while that of the tx gland remained unchanged. The combined data show that the blood flow of a tx pancreas is slightly higher than that of the native organ, and that the response of the islet blood perfusion to glucose administration differs between the native and tx pancreas. This suggests that islets in the tx pancreas 14 days after transplantation are not subject to the same blood flow regulatory mechanisms as native islets.

Animals↗
PubMed1997

Prophylaxis of cytomegalovirus infection in liver transplantation: a randomized trial comparing a combination of ganciclovir and acyclovir to acyclovir. NIDDK Liver Transplantation Database.

BACKGROUND: The optimal prophylactic regimen to prevent cytomegalovirus (CMV) infection and disease in orthotopic liver-transplant patients remains to be established. We tested whether a combination of intravenous ganciclovir (GCV) followed by high dosages of oral acyclovir (ACV) for 4 months provided a higher degree of protection from CMV than oral ACV alone. METHODS: One hundred sixty-seven liver-transplant recipients were randomized to receive 120 days of antiviral treatment starting at the time of transplantation consisting of either ACV 800 mg orally four times daily (n=84) or 14 days of GCV 5 mg/kg intravenously every 12 hr followed by oral ACV 800 mg four times daily (n=83). Prospective laboratory and clinical surveillance was performed to determine primary endpoints (onset of CMV infection and CMV disease) and secondary endpoints (rates of fungal and bacterial infection, allograft rejection, and survival after transplantation). One-year event rates are presented as cumulative percentages. RESULTS: During the first year after transplantation, CMV infection developed in 57% of patients treated with ACV and in 37% of patients treated with GCV + ACV (P=0.001). CMV disease developed in 23% of patients treated with ACV and in 11% of patients treated with GCV + ACV (P=0.03). In seronegative recipients of allografts from CMV-seropositive donors (D+/R-), CMV disease developed in 58% of patients treated with ACV and in 25% of patients treated with GCV + ACV (P=0.04). In the D+/R- group, 54% of patients treated with ACV and 17% of patients treated with GCV + ACV developed infection with Candida albicans (P=0.05). CONCLUSIONS: Prophylaxis of CMV infection in liver-transplant patients with 14 days of intravenous GCV followed by high-dosage oral ACV is more effective than high-dosage oral ACV alone at reducing CMV infection and disease, even for patients in the D+/R- CMV serological group.

Acyclovir↗