Assessment of USDA-NRCS rangeland conservation programs: recommendation for an evidence-based conservation platform.

The Conservation Effects Assessment Project (CEAP) was created in response to a request from the Office of Management and Budget that the U.S. Department of Agriculture, Natural Resource Conservation Service (USDA-NRCS) document the societal benefits anticipated to accrue from a major increase in conservation funding authorized by the 2002 Farm Bill. A comprehensive evaluation of the efficacy of rangeland conservation practices cost-shared with private landowners was unable to evaluate conservation benefits because outcomes were seldom documented. Four interrelated suppositions are presented to examine the causes underlying minimal documentation of conservations outcomes. These suppositions are (1) the benefits of conservation practices are considered a certainty so that documentation in not required, (2) there is minimal knowledge exchange between the USDA-NRCS and research organizations, (3) and a paucity of conservation-relevant science, as well as (4) inadequate technical support for land owners following implementation of conservation practices. We then follow with recommendations to overcome potential barriers to documentation of conservation outcomes identified for each supposition. Collectively, this assessment indicates that the existing conservation practice standards are insufficient to effectively administer large conservation investments on rangelands and that modification of these standards alone will not achieve the goals explicitly stated by CEAP. We recommend that USDA-NRCS modify its conservation programs around a more comprehensive and integrative platform that is capable of implementing evidence-based conservation. Collaborative monitoring organized around landowner-agency-scientist partnerships would represent the focal point of a Conservation Program Assessment Network (CPAN). The primary network objective would be to establish missing information feedback loops between conservation practices and their agricultural and environmental outcomes to promote learning, adaptive management, and innovation. Network information would be archived and made available to guide other, related conservation programs in relevant ecoregions. Restructuring conservation programs as we recommend would (1) provide site specific information, learning, and accountability that has been requested by CEAP and (2) further advance balanced delivery of agricultural production and environmental quality goals.

Roux-en-Y gastric bypass for recurrent nonalcoholic steatohepatitis in liver transplant recipients with morbid obesity.

BACKGROUND: Severe obesity is common before and after liver transplantation and has been associated with significant morbidity and mortality. Furthermore, it may cause graft dysfunction through the development of recurrent nonalcoholic steatohepatitis. METHODS: We performed Roux-en-Y gastric bypass in two morbidly obese patients who had undergone liver transplantation and had graft dysfunction secondary to recurrent nonalcoholic steatohepatitis. RESULTS: Both patients demonstrated dramatic weight loss and had normalization of liver enzymes, lipids, and glucose levels. Repeated liver biopsy showed regression of steatosis. CONCLUSIONS: Roux-en-Y gastric bypass can be successfully performed in liver transplant recipients with morbid obesity and may lead to weight loss, correction of metabolic abnormalities, and regression of hepatic dysfunction secondary to recurrent steatosis.

Diabetic groups as defined by ADA and NDDG criteria have a similar aerobic capacity, blood pressure and body composition. American Diabetes Association and National Diabetes Data Group.

AIMS/HYPOTHESIS: In 1997 the American Diabetes Association (ADA) published new categories for diabetes based on fasting plasma glucose that classified diabetes as a plasma glucose of 7.0 mmol/l, or more, rather than one of 7.8 mmol/l or more, as published previously by the National Diabetes Data Group (NDDG) in 1979. We compared the cardiovascular disease risk factors of subjects classified as having Type II (non-insulin-dependent) diabetes mellitus under the NDDG and ADA criteria. METHODS: We examined a database of approximately 3,700 men (40.4 +/- 11.5 years old) and distributed them into four categories: normal fasting plasma glucose (NFG) of less than 6.1 mmol/l, impaired (IFG) 6.1 to 7.0 mmol/l, ADA diabetic 7.0 to 7.8 mmol/l and NDDG diabetic of 7.8 mmol/l or more. RESULTS: Fasting glucose was 5.2 +/- 0.5, 6.4 +/- 0.2, 7.3 +/- 0.2 and 11.2 +/- 2.9 mmol/l for the subjects of the NFG, IFG, ADA and NDDG groups, respectively. Estimated treadmill VO2max was 41.4 +/- 8.0, 36.0 +/- 7.8, 32.2 +/- 7.6, 30.6 +/- 7.0 ml x kg(-1) x min(-1) in the NFG, IFG, ADA, and NDDG groups, respectively (NFG and IFG > ADA and NDDG: p < 0.05). The ADA and NDDG groups were also similar for resting and exercise blood pressure and body composition. Triglycerides and total: HDL cholesterol ratios were higher and LDL cholesterol concentration was lower, in the NDDG group than in all other groups (p < 0.05). Total and LDL cholesterol in the ADA and NDDG groups were similar. CONCLUSION/INTERPRETATION: The similarities in the aerobic capacities, blood pressure and body composition of the ADA and NDDG groups indicate that the decision to lower the cut-off from 7.8 mmol/l to 7.0 mmol/l blood glucose for the clinical classification of diabetes was appropriate. The ADA and NDDG groups, however, might not have identical risks for cardiovascular disease because of differences between total:HDL cholesterol ratios, circulating HDL cholesterol and triglyceride concentrations.

Plasma C3a and C4a levels in liver transplant recipients: a longitudinal study.

Liver transplant patients were enrolled in a study designed to investigate correlations between plasma complement C3a or C4a levels and various postoperative complications. Longitudinal EDTA-plasma levels of C3a and C4a were measured by quantitative radioimmunoassay. Acute rejection gave a characteristic and marked increase in blood C3a, C4a and gamma-glutamyl transferase (gammaGT) levels, which rapidly resolved after high dose steroid treatment. Cytomegalovirus (CMV) infections in two of three patients gave an initial small increase only in C3a levels (i.e., alternative pathway activation) followed approximately 6 weeks later by a marked increase in C4a levels (i.e., classical or lectin pathway activation). In a third patient diagnosed for CMV infection, the complement activation profile was complicated by a coincident minor rejection episode. However, a late stage elevation in C4a was also noted. Two patients experiencing biopsy proven recurrent hepatitis C infections following transplantation exhibited increases in both gammaGT and C4a levels, without a significant increase in the level of C3a. Several hepatitis C and one hepatitis B patient had multiple late activation episodes involving marked elevation in both plasma C3a and C4a levels without detectable increases in the liver enzymes conventionally used to monitor organ function. We also showed that ex vivo activation of complement in EDTA plasma from all transplant patients was abnormally high. The classical or lectin pathway is believed to be responsible for this excessive ex vivo complement activation in the plasma of these patients. Therefore, subclinical rejection episodes and/or viral infections may be effectively detected or monitored by measuring C3a and C4a levels in plasma samples from liver transplant patients. Routine measurement of plasma complement products may provide an early non-invasive mode for detecting infections and also serve to monitor chronic or acute changes in the patient's immune system.

Increased incidence of rejection in patients with delayed graft function.

Because of the difficulties in diagnosing rejection in patients with delayed graft function, such patients were routinely biopsied 7-10 days after kidney transplantation. We found histologic evidence of rejection in 48% of the cases during the lst month posttransplant, a proportion that was significantly higher than in patients with immediate graft function. Furthermore, the 2-year graft survival in patients with delayed graft function and rejection, but not in those without rejection, was significantly lower than in patients with immediate function. The results suggest that there is an association between delayed graft function and rejection and that rejection is the component responsible for the decreased graft survival previously reported for patients with delayed graft function.

Transplantation of a hepatitis B surface antigen-positive donor liver into a hepatitis B virus-negative recipient.

A critically ill, HBV seronegative girl who received a liver from a HBsAg+ donor is described. Despite HBV Ig prophylaxis, she was seropositive for HBsAg shortly after transplantation. Although the postoperative period was complicated, HBV-related problems were not encountered. Liver dysfunction was noted 7 months after transplantation. At that time, she became anti-HBc IgM-positive, with liver histologic findings suggestive of chronic active hepatitis B. The liver function normalized after a reduction of immunosuppressive therapy and introduction of ciprofloxacin. The patient had low level HBV replication during the entire follow-up period (HBV DNA-positive by PCR only) and sequencing of the virus on 4 occasions revealed only wild-type HBV. She subsequently lost serum HBsAg and HBV DNA (even by PCR) and has remained well 2 years after transplantation.

A preliminary report of diltiazem and ketoconazole. Their cyclosporine-sparing effect and impact on transplant outcome.

A prospective randomized trial was conducted to compare the effect of diltiazem (DILT) with ketoconazole (KETO) on sparing of cyclosporine dose and renal transplant outcome. Renal allograft recipients 18 years old and older were eligible for the study. Triple immunosuppression (TRIPLE) including prednisone, azathioprine, and CsA was administered to all patients. The maintenance CsA dose varied by study group. Patients were randomized to receive one of three treatment strategies: group 1-TRIPLE (CsA 8 mg/kg/day); group 2--TRIPLE (CsA 6 mg/kg/day) + DILT (60 mg b.i.d.); group 3--TRIPLE (CsA 3 mg/kg/day) + KETO (200 mg/day). Modification of the DILT dose was allowed as needed to effect blood pressure control in group 2 patients. Mean 1-month CsA dose reductions were 30% and 60% of controls in group 2 and 3, respectively. A continued effect over time was observed in patients administered KETO but not DILT. At 1 year patients taking KETO required an average of 77% less CsA than the average dose necessary to effect similar parent CsA blood levels when no enzyme inhibitor was used. The use of KETO and DILT for 1 year allowed for 53% and 14% reductions in CsA cost, respectively. These savings include the cost of the KETO or DILT. Serum creatinines, mean arterial pressure (MAP), and incidence of liver function abnormalities were similar throughout treatment groups. The rate of rejection, time to rejection onset, and survival (GS/PS) were not different among the groups. Fungal infections were fewer in patients treated with KETO (12%) than in controls (16%) and patients randomized to DILT (19%). KETO failed to prevent Aspergillus infection in one individual. The investigation failed to identify any harmful result of treating renal allograft recipients with either DILT or KETO for the purpose of reducing CsA expense.

The crossmatch in renal transplantation. Evaluation of flow cytometry as a replacement for standard cytotoxicity.

Flow cytometry (FC) is increasingly being used as a crossmatch procedure in addition to the standard complement-dependent cytotoxicity (CDC) test. In fact, FC offers a number of advantages over CDC and has the potential to become the primary crossmatch technique for cadaveric donor renal transplantation. We evaluated this possibility in 230 patients crossmatched by both CDC and FC. The results showed that when the T cell crossmatch was negative by FC it was always negative by CDC, and that when the T cell results were positive by CDC (IgM antibodies excluded) they were also positive by FC. As expected, a number of tests were T cell-positive by FC but negative by CDC. A T cell CDC crossmatch was more likely to be positive when FC was positive for both T and B cells and when FC results were quantitatively higher. However, FC was unable to consistently predict a positive, dithiothreitol-resistant B cell CDC crossmatch. A policy to transplant patients with negative FC results (70% of the patients evaluated) and not to transplant sensitized patients with FC+ T cell results (10%) would allow us to make a final decision with only FC in 80% of the cases. Actual graft survival was similar for nonsensitized first-transplant candidates with positive (83%) or all patients with negative (86%) FC results. We conclude that FC is sufficient to make a final decision in most cases. Wider utilization will require improvements in the ability of FC to measure B cell antibodies and to quantitate antibodies to T cells.

Non-A, non-B hepatitis and elevated serum aminotransferases in renal transplant patients. Correlation with hepatitis C infection.

One hundred renal transplant recipients were studied for antibodies to hepatitis C virus (HCV), and to HCV RNA in serum by reverse transcription+nested polymerase chain reaction (RT-PCR). Presence of antibody to HCV confirmed by recombinant immunoblot assay II was considered evidence of HCV infection, and detection of HCV RNA by RT-PCR was considered evidence for active viremia. On pretransplant sera, 18 patients were RT-PCR positive and an additional 3 had antibody evidence of HCV infection. At 1-year follow-up, all of these patients were RT-PCR positive and an additional 7 patients became RT-PCR positive. Clinical diagnosis of non-A, non-B hepatitis underestimated the prevalence of HCV infection (5/28 cases, 18%). Serum alanine aminotransferase (ALT) elevations were neither sensitive nor specific. An isolated pretransplant ALT elevation predicted a 52% chance of being RT-PCR positive for HCV. An ALT elevation greater than 2 months after transplant predicted a 45% chance of HCV positivity; however, 18% of patients who never had any ALT abnormality were also HCV positive. Sixty-eight patients had an early postoperative rise in ALT, but there was no correlation with HCV status. After an average follow-up of over 4 years, 3/28 HCV-positive patients developed cirrhosis. HCV infection in the renal transplant population is common and underdiagnosed by clinical and biochemical parameters. HCV appears not to cause aggressive liver disease in the early posttransplant period, but longer follow-up is needed to define the natural history of HCV in the renal transplant population.

Kupffer cells can present alloantigen in vitro: an effect abrogated by gadolinium.

Portal venous (PV) injection of alloantigen can result in tolerance. We have previously reported that this effect is abrogated by pretreatment with gadolinium (Gd), an element known to inhibit Kupffer cell phagocytosis. To further elucidate the role of Kupffer cells (KC) in PV tolerance, the present study examined the ability of KC to present alloantigen in vitro to syngeneic responder lymphocytes after in vivo PV administration of alloantigen with or without pretreatment with Gd. Wistar Furth (WF) rats were pretreated 24 hr prior to KC harvest with a PV injection of 1 x 10(7) allogeneic Lewis (LEW) rat lymphocytes (KC-L) or saline (KC-N). Another group received Gd intravenously 24 h prior to the PV injection of LEW cells (KC-L + Gd). KC were isolated from the WF rats using collagenase digestion and Percoll (90% pure by morphologic criteria and by monoclonal antibodies KU-1 and ED-2). Responder WF lymphocytes were cocultured with media alone, or with KC as prepared above, for 72 hr. KC-L demonstrated significant stimulation of the WF responders (P = 0.02 vs KC-N). Gd abrogated this stimulation (P = 0.04, KC-L vs KC-L + Gd) but not by nonspecific inhibition of the cocultures (KC-N vs KC-L + Gd, P > 0.05, no difference). This study demonstrates that KC can effectively present PV alloantigen for the activation of naive syngeneic T lymphocytes, thereby further supporting the hypothesis that KC play an integral role in the induction of PV tolerance by presentation of antigen to responder T cells.

Hepatitis C virus infection in kidney transplant recipients.

To determine the prevalence and significance of hepatitis C virus infection in kidney transplant recipients, paired serum samples collected from 100 renal allograft recipients on admission for kidney transplantation and 1 yr after transplantation were tested for antibody to hepatitis C virus with second-generation enzyme immunoassay and recombinant immunoblot assay and for hepatitis C virus RNA with reverse transcription-polymerase chain reaction. Before kidney transplantation, hepatitis C virus antibody was detected with second-generation enzyme immunoassay in 18 patients (12 second-generation recombinant immunoblot assay-positive, 6 second-generation recombinant immunoblot assay-indeterminate). Nine of 12 second-generation recombinant immunoblot assay-positive and 2 of 6 second-generation recombinant immunoblot assay-indeterminate samples were hepatitis C virus RNA positive. In addition, 7 of 82 patients who had no detectable antibody on second-generation enzyme immunoassay or second-generation recombinant immunoblot assay were hepatitis C virus RNA positive. After kidney transplantation, hepatitis C virus antibody was detected in 19 patients (12 second-generation recombinant immunoblot assay-positive, 7 second-generation recombinant immunoblot assay-indeterminate, 14 seropositive for hepatitis C virus antibody). Eleven of 12 patients with second-generation recombinant immunoblot assay-positive results and 4 of 7 with second-generation recombinant immunoblot assay-indeterminate results were positive for hepatitis C virus RNA. Hepatitis C virus RNA was present in 28 patients 1 yr after kidney transplantation. Six patients appeared to have acquired active hepatitis C virus infection 1 yr after kidney transplantation (seroconverted to hepatitis C virus RNA positivity).(ABSTRACT TRUNCATED AT 250 WORDS)

Relationship of the polymerase chain reaction for cytomegalovirus to the development of hepatitis in liver transplant recipients.

In a pilot study, the polymerase chain reaction was found to be more sensitive than standard viral culture methods for the detection of cytomegalovirus, particularly from blood and tissues. We therefore applied this technique to 71 serially collected liver biopsies from 16 orthotopic liver transplant patients. All patients were CMV-seropositive (n = 15) or seroconverted (n = 1). Seven patients (9 biopsies) had histologically proved CMV hepatitis, and all these biopsies were CMV PCR-positive. Six of these 7 patients had a prior liver biopsy that was CMV PCR-positive, but culture and histology-negative, an average of 13.2 +/- 6.9 days before the histologically positive biopsy. The 7th patient was not biopsied prior to the diagnostic biopsy. Three patients had 7 liver biopsies that were CMV PCR-positive, but histologically negative for CMV hepatitis. Two of these three had CMV infection confirmed by viral culture of blood or liver biopsy. The remaining 6 patients had a total of 26 liver biopsies that were negative for CMV by PCR, culture, and histology. Among liver transplant patients, CMV PCR performed on liver biopsy specimens correctly identified all histologically proven cases of CMV hepatitis. CMV PCR positivity in liver tissue did not correlate with latent infection and preceded the development of CMV hepatitis or other meaningful CMV infection in 8 of 10 patients.

Psychological adjustment of liver transplant candidates.

The psychological functioning of 20 adult liver transplant candidates was evaluated. Using standardized assessment instruments, we found few personality disturbances and normal levels of anger. However, clinically significant levels of depression and anxiety were reported for 28% and 37% of the sample, respectively. Moreover, patients whose coping strategies were characterized by avoiding the exigencies of their illness reported more depression, more anxiety, and increased psychopathology. Disease severity was also positively correlated with anxiety and avoidant coping strategies. Implications of these findings for the pre-transplant psychological evaluation are discussed.