Social structure of collared peccaries (Pecari tajacu): does relatedness matter?

Relatedness is considered an important factor in shaping social structure as the association among kin might facilitate cooperation via inclusive fitness benefits. We addressed here the influence of relatedness on the social structure of a Neotropical ungulate, the collared peccary (Pecari tajacu). As peccaries are highly social and cooperative, live in stable cohesive herds and show certain degree of female philopatry and high mean relatedness within herds, we hypothesized that kin would be spatially closer and display more amicable and less agonistic interactions than non-kin. We recorded spatial association patterns and rates of interactions of two captive groups. Pairwise relatedness was calculated based on microsatellite data. As predicted, we found that kin were spatially closer than non-kin, which suggests that relatedness is a good predictor of spatial association in peccaries. However, relatedness did not predict the rates of social interactions. Although our results indirectly indicate some role of sex, age and familiarity, further studies are needed to clarify the factors that shape the rates of interactions in collared peccaries. This article is part of a Special Issue entitled: Neotropical Behaviour.

Retrospective evaluation of the risk of hepatitis B virus reactivation after transplantation.

Numerous case reports describe patients with previously documented immunity developing active hepatitis B virus (HBV) infection after transplantation. However, the risk of reactivation of HBV under long-term immunosuppression in hepatitis B core antibody (HBcAb)-positive, hepatitis B surface antigen (HBsAg)-negative transplant recipients has not been clearly described. Herein, we present a long-term follow-up for 49 HBcAb-positive, HBsAg-negative recipients (27 liver, 18 kidney, 4 pancreas) transplanted between June 1996 and April 2001. Among these, 37 recipients (76%) were HBsAb positive at transplantation. Immunosuppression consisted of various antibody induction regimens in 20 (41%) of the recipients with either tacrolimus (33 [67%])- or cyclosporine (16 [33%])-based maintenance immunosuppression. The incidence and duration of HBV prophylaxis was not significant. No patient received hepatitis B immunoglobulin (HBIG) before or after transplantation. Additionally, only two patients received lamivudine, which was started post transplant without clinical indication. The mean length of follow-up was 3.1+/-1.4 years. At the last follow-up, overall patient and graft survival were 98% and 96%, respectively. Patient survival was 96% in liver, 100% in kidney, and 100% in pancreas transplant recipients. The graft survival for each organ type was 93% in liver, 100% in kidney, and 75% in pancreas transplant recipients at the end of follow-up. There was no incidence of HBV reactivation defined as recurrence of HBsAg and/or HBV DNA positivity. These data suggest that the risk of reactivation of HBV in HBcAb-positive, HBsAg-negative transplant recipients under immunosuppression is negligible, regardless of immunosuppressive regimen, lamivudine prophylaxis, or HBsAb status. These patients should have access to transplantation as they enjoy excellent patient and graft survival rates.

Polyomavirus in kidney and kidney-pancreas transplant recipients.

PURPOSE: To report the incidence and clinical characteristics of polyomavirus (PV) nephritis in kidney (KTX) and kidney-pancreas transplant (KPTX) recipients. METHODS: Single center retrospective analysis of all cases of PV nephritis in KTX and KPTX patients transplanted between 1994 and 1999. RESULTS: Thirteen (5 KTX and 8 KPTX) patients (2.1%) had PV nephritis diagnosed on multiple biopsies (n = 22) among 504 KTX and 106 KPTX recipients. The incidence of PV nephritis was higher in cadaver donor transplants (2.6% cadaver vs. 0.7% living donors), after KPTX (1% KTX vs. 7.5% KPTX), in males (3.3% male vs. 0.7% female), and in diabetic patients (4.4% diabetic vs. 0.8% nondiabetic). The mean time to diagnosis of PV nephritis was 18 (range 6-48) months after KTX and 17 (range 9-31) months after KPTX. Three KTX patients and 5 KPTX patients had calcineurin inhibitor toxicity on biopsy prior to developing PV nephritis. Reduction in immunosuppression occurred in 100% of KTX and 63% of KPTX patients. Three patients (23%) developed rejection within 3 months of diagnosis of PV, 1 after a reduction in immunosuppression. Despite multiple antiviral treatment regimens, renal allograft failure requiring dialysis occurred in 60% of KTX and 50% of KPTX patients. All KPTX patients remain insulin independent and 2 were successfully retransplanted with living donor kidneys. 2 patients (15%) died but there was no mortality directly related to the virus. CONCLUSIONS: Polyomavirus nephritis may be increasing in incidence and appears to be unresponsive to either conventional antiviral agents or a reduction in immunosuppression. Most of our cases occurred in male diabetic patients undergoing cadaveric donor transplantation and were preceded by biopsy-proven nephrotoxicity. Further studies are needed to better define the pathogenesis of PV and effective antiviral treatment.

Evolving experience of hepatitis B virus prophylaxis in liver transplantation.

Passive immunoprophylaxis with hepatitis B immunoglobulin (HBIG) is important to prevent recurrence of hepatitis B virus (HBV) after orthotopic liver transplantation (OLT) for chronic HBV cirrhosis. With availability of lamivudine (3TC), the use of combination prophylaxis with long-term HBIG/3TC has been shown to prevent short-term HBV recurrence. This report compares HBV recurrence rates between groups receiving no/short-term HBIG, long-term HBIG alone, or HBIG/3TC prophylaxis, and describes HBIG requirements during the first 6 and 12 months in the latter two groups. This study involved patients undergoing OLT at the University of Tennessee-Memphis between May 1990 and July 2001. During this period, 388 liver transplants were performed at our center. All hepatitis B surface antigen (HBsAg)-positive recipients (n = 27) were included in this retrospective analysis. The groups were similar with regard to pre-transplant demographic characteristics such as age, gender, weight, and pre-transplant diagnosis. Owing to the retrospective study design, median follow-up was longer for the no-prophylaxis (5.6 years) and the HBIG-alone (6.0 years) groups compared to the HBIG/3TC group (4.2 years). Patient survival was 50% in the no-prophylaxis and 71% in the HBIG-alone groups compared to 100% in the HBIG/3TC group (P = 0.09). When censored for death with a functioning graft, graft survival was 50% in the no-prophylaxis and 86% in the HBIG-alone group compared to 100% in the HBIG/3TC group (P = 0.07). The overall incidence of HBV recurrence in the no-prophylaxis era was 100% and 21% in the HBIG-alone era compared to 0% in the HBIG/3TC era (P < 0.001), despite similar mean and median HBIG trough titers in the HBIG-alone and HBIG/3TC groups. The incidence of HBV recurrence in HBV DNA-positive recipients was 100% in the no-prophylaxis era, 30% in the HBIG-alone era, and 0% in the HBIG/3TC era (P < 0.001). Recipients in the HBIG-alone group had a nearly two-fold increase in HBIG requirement at 6 and 12 months in order to maintain similar HBIG trough titers post-transplant compared to recipients in the HBIG/3TC group despite similar pre-transplant HBV serology. This increased HBIG requirement in the HBIG-alone group resulted in a marked increase in the mean overall cost of HBV prophylaxis in this group ($47,367 US dollars at 6 months; $84,280 US dollars at 12 months) compared to the HBIG/3TC group ($25,931 US dollars at 6 months; $49,599 US dollars at 12 months). These data demonstrate an improvement in patient and graft survival rates in the group receiving combination HBIG/3TC prophylaxis compared to the HBIG-alone and no-prophylaxis groups. There was a significant reduction in HBV recurrence in the group receiving combination HBIG/3TC when compared to the groups receiving HBIG alone or no prophylaxis. Furthermore, we demonstrated that the addition of 3TC to the long-term HBIG regimen led to elimination of the disparity previously described in HBV recurrence rates between HBV DNA-positive and HBV DNA-negative recipients. Importantly, our data demonstrates a complete lack of HBV recurrence in the HBIG/3TC group at a median follow-up of 4.2 years. Additionally, the data show that the addition of 3TC to the post-operative prophylaxis regimen resulted in a reduction in the requirement of HBIG at 6 and 12 months, which markedly reduced the overall cost of post-transplant HBV prophylaxis.

Choice of surgical technique influences perioperative outcomes in liver transplantation.

OBJECTIVE: To examine how the choice of surgical technique influenced perioperative outcomes in liver transplantation. SUMMARY BACKGROUND DATA: The standard technique of orthotopic liver transplantation with venovenous bypass (VVB) is commonly used to facilitate hemodynamic stability. However, this traditional procedure is associated with unique complications that can be avoided by using the technique of liver resection without caval excision (the piggyback technique). METHODS: A prospective comparison of the two procedures was conducted in 90 patients (34 piggyback and 56 with VVB) during a 2.5-year period. Although both groups had similar donor and recipient demographic characteristics, posttransplant outcomes were significantly better for the patients undergoing the piggyback technique. The effect of surgical technique was examined using a stepwise approach that considered its impact on two levels of perioperative and postoperative events. RESULTS: The analysis of the first level of perioperative events found that the piggyback procedure resulted in a 50% decrease in the duration of the anhepatic phase. The analysis of the second level of perioperative events found a significant relation between the anhepatic phase and the duration of surgery and between the anhepatic phase and the need for blood replacement. The analysis of the first level of postoperative events found that the intensive care unit stay was significantly related to both the duration of surgery and the need for blood replacement. The intensive care unit stay was in turn related to the second level of postoperative events, namely the length of hospital stay. Finally, total charges were directly related to length of hospital stay. The overall 1-year actuarial patient and graft survival rates were 94% in the piggyback and 96% in the VVB groups, respectively. CONCLUSIONS: These data demonstrate that surgical choices in complex procedures such as orthotopic liver transplantation trigger a chain of events that can significantly affect resource utilization. In the current healthcare climate, examination of the sequence of events that follow a specific treatment may provide a more complete framework for choosing between treatment alternatives.

Eighteen years of experience with adult and pediatric liver transplantation at the University of Tennessee, Memphis.

1. Since its inception, the liver program at UT Memphis has been striving to serve its population by stressing access, technical innovation, and by its focus on quality of life. The results for both adult and pediatric transplants over the past 18 years demonstrate that small and medium-sized programs can function efficiently and are valuable for their local communities. 2. Patient and graft survival rates exceeded 85% in the pediatric population in the first year with the 5-, 10-, and 15-year results above 75%. 3. Patient and graft survival rates in adults were 83% at one year, 68% at 5 years, and 60% at 10 years. 4. Innovative techniques in liver transplantation have had a dramatic impact on accessibility of pediatric recipients to liver transplantation and recently are becoming crucial for select populations of adults requiring expedited transplantation.

Routine early biopsy of allografts with delayed function: correlation of histopathology and transplant outcome.

Approximately 25-30% or our cadaveric renal transplant recipients have required post-transplant dialysis. In an attempt to discern the etiology, routine biopsies were performed 7-10 d post-transplant and repeated weekly. All patients received a triple-therapy cyclosporine-based regimen with (N = 61) or without (N = 10) antilymphocyte induction. Rejection was classified as 'early' when it appeared on the first biopsy (8.9 +/- 0.3 d), 'delayed' when it appeared only on the second biopsy (17.9 +/- 1.0 d) and persistent when present on both biopsies. Adequate biopsy material was obtained from 71 patients who provided a total of 117 biopsies. Acute tubular necrosis was the most common finding (50%) in the first biopsy, while rejection occurred in 30% of biopsies. Rejection on the first biopsy was strongly associated with primary nonfunction (PNF) (8 of 21 vs. 1 of 40, p < or = 0.0001). In contrast, eight patients without rejection on Biopsy 1 developed delayed rejection on Biopsy 2; only one was associated with PNF. DGF persisted beyond the second week in 38 patients; 17 (38%) of which had rejection. Nine patients had persistent rejection 55% of whom experienced PNF compared to 6% without persistent rejection (p < or = 0.001). The occurrence of early rejection was associated with pretransplant peak PRA levels > 50% (p < or = 0.01). Graft survival for all patients was 79% and 65% at 1 and 2 yr. Rejection influenced 1-yr graft survival for patients with persistent rejection who had 55% incidence of primary nonfunction and 1- and 2-yr graft survival rates of 42% and 37%. These data indicate that early biopsies are useful in unmasking rejection during DGF and at predicting primary nonfunction. Based on these data we recommend the routine utilization of biopsies for all patients with DGF.

Prevention of hepatitis B recurrence with indefinite hepatitis B immune globulin (HBIG) prophylaxis after liver transplantation.

Liver transplantation for hepatitis B is followed by a high rate of recurrence some time after transplantation, resulting in poor outcome compared to liver recipients transplanted for other indications. Passive immunoprophylaxis with HBIG has been shown to decrease the rate of recurrence to 25-50%, but the intensity and length of treatment is still controversial. We studied 17 HBsAg positive patients who were transplanted for hepatitis B. Four did not receive immunoprophylaxis and they all reoccurred within 3 months. The remaining 13 have received indefinite, high dose HBIG (10,000 mu or 40,000 mu/dose depending on HBV DNA status pretransplant). Ten of 13 patients (77%) remain HBsAg negative after a mean follow-up of 16.7 months with six of these ten patients being HBV DNA positive pretransplant. Of the three who have experienced recurrence, two received extensive additional immunosuppression beyond that normally administered to transplant patients (chemotherapy, multiple antirejection treatment). The last patient received 110,000 u of HBIG during the first 3 months, which produced an anti-HBs titer level of 225 IU/L, but the following month he was HBsAg positive with an anti-HBs titer of 13 IU/L. We conclude that HBsAg positive patients can be safely transplanted using indefinite, high-dose HBIG prophylaxis, and that with adequate HBIG it is possible to prevent recurrence in HBV DNA positive patients as well.

Clinical observations of metabolic changes occurring in renal transplant recipients receiving ketoconazole.

Metabolism of cyclosporine is reduced by ketoconazole binding to the monooxygenase responsible for cyclosporine degradation. This isozyme of cytochrome P450, along with other similar monooxygenases, is involved in the regulation of the synthesis and degradation of important metabolic pathways of cholesterol. Monooxygenases throughout these pathways are inhibited by ketoconazole binding causing a decreased metabolism of calcitriol, bile acids, and steroid hormones, and can thereby potentiate altered lipid metabolism, bone metabolism, and weight status of transplant recipients. A group of renal transplant recipients taking ketoconazole (n=25) was compared with a matched cohort not receiving ketoconazole for metabolic changes during the first six months posttransplantation. Lower LDL cholesterol levels were seen in the ketoconazole group (109 +/- 8 mg/dl) than the no ketoconazole group (140 +/- 8 mg/dl) at one month but this difference was not sustained at six months. More bone loss occurred in the ketoconazole group as demonstrated by significant changes in bone density as well as a greater urinary appearance of bone collagen crosslink, deoxy-pyridinoline (29 +/- 4 nmol dpd/mmol creatinine and 18 +/- 4 at six months for the ketoconazole group versus the no ketoconazole group, respectively, P<0.05). Weight gain changes were different between the ketoconazole group and no ketoconazole group (6.4 +/- 1.4 kg versus 5.0 +/- 1.3 kg) at six months and an increased rate of weight gain over time in the ketoconazole group (0.02 kg/day at one month versus 0.05 kg/day at six months, P<0.007). Effectiveness of ketoconazole inhibition of cyclosporine is valuable, but inhibition of other metabolic pathways should be evaluated as well.

Glomerulosclerosis as a determinant of posttransplant function of older donor renal allografts.

Transplantation of kidneys from older donors is being advocated to expand the organ donor pool. However, the prevalence of atherosclerosis and age-induced renal structural alterations account for the variable function of allografts procured from these older donors. Pretransplant biopsies are sometimes used to evaluate kidneys from older donors, but to date there are no defined criteria correlating the extent of structural alterations in these kidneys to subsequent function. We investigated the effect of glomerulosclerosis, a marker for nephrosclerosis, on graft outcome. Sixty-five baseline biopsies of kidney allografts were retrospectively analyzed to identify a referent point of glomerulosclerosis that correlated with inferior graft outcome. Age and death from nontraumatic cerebrovascular injuries were the main correlates for donor glomerulosclerosis (P < 0.001). Allografts with poor function at 6 months defined as serum creatinine > 2.5 mg/dl (n = 13) or nephrectomy (n = 4) had a mean of 20% glomerulosclerosis at the time of implantation compared with only 2% sclerosis in allografts with good function (P < 0.05). Delayed graft function occurred in 22% and 33% of recipients with no glomerulosclerosis and those with less than 20% glomerulosclerosis, respectively. In contrast, patients receiving kidneys with > 20% sclerosis had an 87% incidence of delayed function (P < 0.05). Moreover, graft loss occurred in 7% of recipients of kidneys with less than 20% sclerosis and in 38% of recipients with > 20% sclerosis (P < 0.04). Measurements of serum creatinine in the donors did not distinguish the different degrees of glomerulosclerosis found on biopsy. Our data indicate that donor glomerulosclerosis greater than 20% increases the risk of delayed graft function and poor outcome of transplanted kidneys. Therefore, we advocate the use of routine biopsies of kidneys from older (> 50 yrs) donors and those donors with nontraumatic cerebrovascular accidents, despite seemingly normal preprocurement serum creatinine.

Randomized double-blind study of standard versus low-dose OKT3 induction therapy in renal allograft recipients.

A double-blind, randomized, prospective study was undertaken to determine if the dose of OKT3 used for induction immunosuppression following kidney and kidney-pancreas transplantation affected clinical outcomes. Twenty-five patients were randomized in each group. Five patients in each group received a combined kidney/pancreas transplant. All patients received sequential quadruple immune suppression (azathioprine and methylprednisolone, followed by oral prednisone and cyclosporine A), regardless of randomization to the standard (5 mg) or low-dose (2 mg) OKT3 group. OKT3 was administered for 7 to 14 days. The dose of OKT3 was adjusted to ascertain the clearance of peripheral positive CD3 lymphocytes. The mean cumulative OKT3 dose for the standard dose group was 52.0 mg versus 23.4 mg for the low-dose group (P < 0.00001). Dosage increases were necessary for 29% of the standard dose and 32% of the low-dose patients. The side effect score for the standard versus low-dose group was not statistically different (0.79 +/- 0.58 v 0.84 +/- 0.68), except for chills, which occurred more frequently in the low-dose-treated patients (P = 0.003). Anti-OKT3 antibodies developed with similar frequency in both dosage groups, with 8% exhibiting titers of 1:500 or greater at the end of treatment. Kidney graft survival was 96% for the standard dose and 92% for the low-dose group. The overall incidence of rejection was similar in both groups; however the low-dose group did experience an increase in early rejection episodes. The incidence of major and minor viral and bacterial infections was also similar for both dosage groups.(ABSTRACT TRUNCATED AT 250 WORDS)