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R Mañez

Publications and source records attributed to R Mañez.

At least 19 recordsLinked to original sources
PubMed2001

Removal of bowel aerobic gram-negative bacteria is more effective than immunosuppression with cyclophosphamide and steroids to decrease natural alpha-galactosyl IgG antibodies.

Natural alpha-Galactosyl (Gal) antibodies play an important role in the rejection of pig xenografts by humans and Old World monkeys. In this study we investigate the efficacy of two different strategies to reduce the serum level of natural anti-Gal antibodies. On the one hand, removal of aerobic gram-negative bacteria from the intestinal flora, because anti-Gal antibodies appear to be produced as a result of the continuous sensitization by these microorganisms. On the other hand, we studied the effect on these antibodies of an immunosuppressive regimen of cyclophosphamide and steroids. Ten baboons were treated for three months with norfloxacin (Nor Group; n=6) or cyclophosphamide and steroids (CyP Group; n=4). A further four baboons did not receive any treatment (Control Group). Aerobic gram-negative bacteria became negative in stools of the Nor Group after two weeks of treatment, and remained undetectable until week 7. Thereafter, a gradual increase on the fecal concentration of aerobic gram-negative bacteria was observed despite the norfloxacin treatment. The mean anti-Gal IgG in the Nor Group gradually declined from week 4 to 9 to a mean of 62.7 +/- 18% of the baseline level, and during this period were significantly lower than in the CyP (P<0.02) and the Control (P<0.05) groups. No differences were observed between the three groups during the 16 weeks of follow-up in serum levels of anti-Gal IgM, hemolytic anti-pig antibodies, total IgG, IgM and IgA. In conclusion, removal of normal aerobic gram-negative bacteria from the intestinal flora is more effective than immunosuppression with CyP and steroids in reducing the level of natural anti-Gal antibodies, although there is no discernible effect on IgM antibodies.

Animals↗
PubMed1997

Use of DNA amplification for diagnosis of cytomegalovirus enteritis after intestinal transplantation.

BACKGROUND & AIMS: Intestinal transplantation is a feasible therapy for patients with short-bowel syndrome. However, cytomegalovirus (CMV) enteritis can cause complications. The aim of this study was to investigate the value of polymerase chain reaction (PCR)-based detection methods for CMV in the management of patients with small bowel transplants. METHODS: Comparative evaluation of PCR with histopathology, shell-vial assay, and tube culture of intestinal biopsy specimens was used for the diagnosis of CMV enteritis in 21 patients. RESULTS: Ten patients experienced 21 episodes of CMV enteritis, diagnosed by histopathology, virology, or both. PCR had a sensitivity and specificity of 96% and 69%, respectively, compared with traditional methods, whereas the positive and negative predictive values were 35% and 99%, respectively. Three+ and 4+ signals corresponded to a specificity of 91% and positive predictive value of 59%, respectively. CMV was detected by PCR a median of 11 days (range, 0-32) earlier than other methods and lasted a median of 40 days (range, 21-80) in the 13 episodes, which became PCR-negative and in those patients who developed asymptomatic infection. In 8 episodes, CMV by PCR never became negative and was associated with a relapse of disease confirmed by other methods. CONCLUSIONS: PCR is a sensitive method for the early detection of CMV in intestinal biopsy specimens and can be used for preemptive therapy after intestinal transplantation.

Adult↗
PubMed1997

Posttransplant lymphoproliferative disease in primary Epstein-Barr virus infection after liver transplantation: the role of cytomegalovirus disease.

Epstein-Barr virus (EBV) plays a major role in the pathogenesis of posttransplant lymphoproliferative disease (PTLD). Patients who undergo primary EBV infection after transplantation are at greater risk of developing PTLD. In this retrospective study, the incidence of EBV infection and associated PTLD in 40 consecutive adult recipients who were seronegative for EBV at the time of liver transplantation were investigated, and risk factors for PTLD were analyzed. Of 37 patients with available timely posttransplant serum samples, 35 (95%) developed primary EBV infection. Of the 40 patients, 13 (33%) developed PTLD a median of 126 days (range, 48-776) after liver transplantation. The factor significantly associated with the development of PTLD was cytomegalovirus disease (relative risk, 7.3; 95% confidence interval, 2.36-22.6; P = .0006). Cytomegalovirus disease is a predictor for the development of PTLD in primary EBV infection after liver transplantation, and it may be a target for prophylactic intervention.

Adult↗
PubMed1996

Factors associated with the development of candidemia and candidemia-related death among liver transplant recipients.

OBJECTIVE: The authors' objective was to identify factors associated with candidemia and candidemia-related death among adult liver transplant recipients. SUMMARY BACKGROUND DATA: Invasive candidiasis is the most common severe fungal infection occurring after liver transplantation and is associated with high morbidity and mortality rates. Although candidemia is not always found during invasive candidiasis, it has been considered as an indicator of invasive candidiasis in immunocompromised patients. METHODS: A time-matched case-control study of 26 patients with candidemia, which was defined as the isolation of Candida from at least one blood culture, and 52 control patients without candidemia was reported. Two control patients were matched with each case patient regarding time of transplantation and duration of follow-up. RESULTS: Between December 1985 and December 1992, candidemia developed in 1.4% of adult liver transplant recipients a median of 25 days after transplantation (range, 2-1690 days). The overall mortality rate among patients with candidemia was 81%, and 71% of these deaths were related to candidemia. Conditional logistic regression analysis was used to identify factors associated with candidemia, which were 1) hyperglycemia treated with insulin up to 2 weeks before candidemia (odds ratio [OR], 16.15; p = 0.002), and 2) exposure to more than three different intravenous antibiotics before development of candidemia (OR, 11.15; p = 0.005). The variables predictive of death related to candidemia were abdominal surgery performed up to 1 week before candidemia (relative risk [RR], 7.25; p = 0.02), high white blood cell count (RR, 1.10; p = 0.01), lower platelet count (RR, 0.99; p = 0.02), and elevated AST with candidemia (RR, 1.001; p = 0.01). CONCLUSIONS: Hyperglycemia that requires insulin and exposure to more than three antibiotics are the factors associated with the development of candidemia in liver transplant recipients. When candidemia develops shortly after abdominal surgery and in patients with elevated AST, high white blood cell count, or low platelet count, it is associated with a high mortality rate.

Adult↗
PubMed1995

Incidence and risk factors associated with the development of cytomegalovirus disease after intestinal transplantation.

From May 1990 to March 1993, 38 patients (21 adults and 17 children) received 40 allografts that included the small bowel (14 isolated small bowel, 21 small bowel and liver, and 5 multivisceral transplantations). Fifteen patients (39%) had 26 episodes of CMV disease: 7 with one episode, 6 with two, and 1 each with three and four. CMV enteritis accounted for 21 (81%) of the episodes, hepatitis and pneumonitis for 2 each, and a viral syndrome for 1. Cox's proportional hazards univariate and multivariate analyses showed that significant first-episode risk factors were: CMV seropositive donors for negative recipients (relative risk [RR], 3.86; P = 0.02), the average daily plasma trough level of tacrolimus (RR, 2.15; P = 0.04), and total amount of steroid boluses (RR, 2.90; P = 0.02). CMV disease recurrence factors were: CMV seronegative recipients (RR, 8.60; P = 0.02) and total amount of steroid bolus pulses (RR, 12.39; P = 0.004). Because long courses of ganciclovir prophylaxis could not prevent the development of CMV disease, avoidance of CMV seropositive grafts in seronegative recipients and new strategies to prevent heavy immunosuppression without the penalty of rejection will be necessary to ameliorate this problem in intestinal transplant recipients.

Adolescent↗
PubMed1995

Immunoglobulin G lymphocytotoxic antibodies in clinical liver transplantation: studies toward further defining their significance.

Twenty-two consecutive liver allograft recipients, who tested positive for immunoglobulin G (IgG) lymphocytotoxicity were subjected to pretransplantation and posttransplantation immunologic monitoring of anti-donor IgG lymphocytotoxic antibody titers, total hemolytic complement activity (CH100), circulating immune complexes (CIC), and platelet counts in an effort to improve our understanding of the preformed antibody state in clinical hepatic transplantation. Ten contemporaneous liver transplant recipients whose crossmatch results were negative and who experienced severe hepatocellular damage early after transplantation were included as controls. Crossmatch test results were negative 1 day after transplantation and during the 1 month follow-up remained negative in 14 of 22 (64%) sensitized recipients, most of whom had relatively low (< or = 1:16) anti-donor IgG antibody titers before transplantation. After transplantation, this group and the control group experienced no thrombocytopenia, no increase of CIC, and a gradual increase in CH100 activity that reached normal levels within 1 week. A strong negative correlation between prothrombin time (PT) and CH100 activity in these groups of patients suggested that changes in CH100 activity (P < .0005) were tightly linked to liver synthetic function. In contrast, the crossmatch test results remained positive after transplantation in 8 of 22 (36%) sensitized recipients, all of whom had relatively high (> 1:32 to 1024) pretransplantation titers of anti-donor IgG antibodies. After transplantation these patients developed a syndrome that was characterized by decreased CH100 activity and increased CIC compared with pretransplantation levels and refractory thrombocytopenia that was associated with a 50% allograft failure rate because of biopsy-proven humoral and acute (cellular) rejection.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

A prospective randomized trial comparing sequential ganciclovir-high dose acyclovir to high dose acyclovir for prevention of cytomegalovirus disease in adult liver transplant recipients.

Cytomegalovirus disease is an important cause of morbidity following liver transplantation. To date there has not been an effective prophylaxis for CMV disease after liver transplantation. One hundred forty-three patients were randomized to receive either high dose oral acyclovir (800 mg 4 times a day) alone for 3 months after transplantation (acyclovir group) or intravenous ganciclovir (5 mg/kg twice a day) for 14 days followed by high dose oral acyclovir to complete a 3-month regimen (ganciclovir group). Of 139 patients available for evaluation, 43 of 71 (61%) patients from the acyclovir group developed CMV infection compared with 16 of 68 (24%) from the ganciclovir group (relative risk, 3.69; 95% confidence interval, 2.07-6.56; P < 0.00001). Of those randomized, CMV disease was seen in 20 (28%) of the acyclovir group compared with 6 (9%) of the ganciclovir group (relative risk, 5.11; 95% confidence interval, 2.05-12.75; P = 0.0001). The median time to onset of CMV infection was 45 days in the acyclovir group compared with 78 days in the ganciclovir group (P = 0.004). The median time to onset of CMV disease was 40 days in the acyclovir group compared with 78 days in the ganciclovir patients (P = 0.02). With respect to primary CMV infection, there was no difference in the rates in the 2 groups, but tissue invasive disease and recurrent CMV disease were less frequent in the ganciclovir group. It is concluded that a course of 2 weeks of ganciclovir immediately after transplantation followed by high dose oral acyclovir for 10 weeks is superior to a 12-week course of high dose oral acyclovir alone for prevention of both CMV infection and CMV disease after liver transplantation. However, the lack of significant effect in seronegative recipients who received grafts from seropositive donors suggests that other strategies are needed to prevent CMV infection in this high risk population.

Acyclovir↗
PubMed1994

Factors associated with the development of post-transplant lymphoproliferative disease (PTLD) in Epstein-Barr virus (EBV)-seronegative adult liver transplant recipients.

Epstein-Barr virus (EBV) infection is recognized as the principal aetiological factor in the pathogenesis of post-transplant lymphoproliferative disease (PTLD), particularly when primary EBV infection occurs after transplantation. We analysed, using a time-dependent proportional hazards model, the factors associated with development of PTLD in 40 adult liver transplant recipients who were seronegative for EBV prior to transplantation. Of 40 patients, 13 (33%) had a tissue diagnosis of PTLD at a median time of 126 days after transplantation. The multivariate analysis showed that prior CMV disease, the number of steroid boluses given and the number of units of RBC and FFP transfused were significant risk factors for development of PTLD.

Adult↗
PubMed1994

Diagnosis of cytomegalovirus infections by shell vial assay and conventional cell culture during antiviral prophylaxis.

A total of 3,552 specimens for conventional cytomegalovirus (CMV) culture and shell vial assay for CMV immediate-early antigen were obtained during a prospective randomized trial for prophylaxis of CMV disease after liver transplantation. Prophylaxis with ganciclovir for 2 weeks and then high-dose acyclovir for 2.5 months was compared with high-dose acyclovir alone for 3 months. During the first 12 weeks after transplantation, when the patients were on prophylaxis, there were significantly more clinical samples positive by the shell vial assay and negative by standard culture in comparison with the number of samples obtained from weeks 13 to 24, after prophylaxis was discontinued, that were positive by the shell vial assay and negative by standard culture. In contrast, significantly fewer samples were positive by both the shell vial assay and standard culture during the first 12 weeks compared with the number obtained 13 to 24 weeks after transplantation that were positive by both methods. Samples positive by the shell vial assay only were obtained significantly more frequently from patients with asymptomatic than symptomatic CMV infections, while samples positive by both methods were obtained significantly more often from patients with symptomatic CMV infection. It was concluded that antiviral prophylaxis with high-dose acyclovir or ganciclovir and then high-dose acyclovir and asymptomatic CMV infection are associated with a decrease in the level of CMV isolation by standard cell culture in comparison with that by the shell vial assay.

Acyclovir↗