Immunological profile of patients awaiting a renal transplant

BACKGROUND: A renal transplant is the best possible treatment for patients with terminal renal failure. Advances in the development of techniques of screening of pre-formed antibodies have contributed to a notable improvement in the results obtained with allogenic transplants. METHODS: The aim of the present work is to study the nature, class, isotype and specificity of antibodies detected in patients awaiting renal transplantation at Complejo Hospitalario Universitario Juan Canalejo, as well as their relation with the level of anti-human leucocyte antigen (HLA) sensitization. RESULTS: In all patient groups, there was a predominance of IgG. The distribution of anti-HLA antibody class showed that the most frequent pattern corresponded to a mixture of class I and class II antibodies for all groups. The study of specificity of anti-HLA antibody showed that of the patients with at least one previous transplant, 72% developed specific anti-HLA antibodies against some of the incompatible antigens of the donor, 12% against HLA antigens not related with the phenotype of the donor and in 16% it was not possible to determine their specificity. Most patients developed antibodies against antigens of locus B, probably because of that the number of incompatibilities contributed by the donors is also greater for locus B. CONCLUSIONS: The exhaustive study of sera of patients on a waiting list for transplantation with respect to the nature, isotype, class and specificity of the antibody is important since it is possible that different antibodies can bring about, in the transplant, events that will have different consequences for the survival of the graft.     

Short communication: liver toxicity of lopinavir-containing regimens in HIV-infected patients with or without hepatitis C coinfection

Liver toxicity is a common side effect of antiretroviral therapy, particularly in subjects coinfected with the hepatitis C virus (HCV). The incidence of severe liver toxicity after initiation of treatment with lopinavir (LPV) as well as its possible association with LPV plasma levels were assessed in 120 HIV-infected patients (52% coinfected by HCV). The incidence of severe liver toxicity at 3 months was 1.7% and the cumulative incidence at 12 months was 4%. The development of severe liver toxicity was associated with HCV coinfection but not with LPV plasma levels.     

Absence of Meissner corpuscles in the digital pads of mice lacking functional TrkB

The TrkB-expressing sensory neurons seem to be involved in touch and other discriminative sensibilities. Thus, several slowly and rapidly adapting cutaneous mechanoreceptors, as well as muscle spindles, are reduced or absent in the territory of the trigeminal nerve in functionally TrkB-deficient mice. Whether this also occurs in the cutaneous or muscular territories of dorsal root ganglia has not been analyzed. Here we used immunohistochemistry and transmission-electron microscopy to analyze the impact of a mutation in the gene coding for TrkB on Meissner and Pacinian corpuscles, and muscle spindles. The animals were studied at the post-natal days 15 and 25, because at this time all the mechanoreceptors examined are fully developed. Typical Meissner's corpuscles, displaying S-100 protein immunoreactivity, were found in the digital pads of wild-type and TrkB+/- mice whereas they were absent in the TrkB-/- animals. Regarding Pacinian corpuscles, the mutation in the trkB gene does not alter either the immunohistochemical or the ultrastructural characteristics. Finally, in muscle spindles the arrangement of the intrafusal muscle fibers and nerve fibers was unchanged in the mutated animals. Nevertheless, about 10% of muscle spindles showed increased number of the intrafusal cells (between 6 and 12) and were supplied by more than one large myelinic nerve fiber. The present results strongly suggest that TrkB-expressing sensory neurons in dorsal root ganglia, like those of the trigeminal ganglion, are responsible for the development and maintenance of several rapidly adapting cutaneous mechanoreceptors, i.e. Meissner's corpuscles.     

Acquired and inherited thrombophilia in women with unexplained fetal losses

OBJECTIVE: The purpose of this study was to investigate the possible role of inherited and acquired thrombophilia in women with unexplained abortions and intrauterine fetal death. STUDY DESIGN: We included 75 women with >/=1 unexplained fetal loss, and 75 control subjects with at least 1 healthy term infant and without gestational complications. All of these women were tested for mutations of factor V Leiden, methylenetetrahydrofolate reductase, and prothrombin gene; deficiencies of antithrombin-III, protein C, and protein S; and the presence of antiphospholipid antibodies and fasting homocysteine concentration. A placental histologic study was also carried out. RESULTS: Thirty-five percent of the 75 patients had thrombophilia (control subjects, 16%; P =.008; odds ratio, 2.78). This prevalence was more prominent in second and third trimesters (P =.0002; odds ratio, 6.3), and the presence of combined genetic defects was associated with intrauterine fetal death (P =.04; odds ratio, 12; 95% CI, 1.44-102). When we analyzed the overall gestations of the patients, we observed an increase of intrauterine fetal death in patients with thrombophilia (P =.01) and early pregnancy loss in patients without thrombophilia (P =.02). The analysis of the correlation between extensive placental infarctions and thrombophilic defects rendered values in the boundaries of significance (P =.05). CONCLUSION: The significant high prevalence of biologic causes in patients with late fetal loss suggests that a study of thrombophilia should be carried out, together with an assessment of a preventive treatment.     

Disparity in total hip replacement affecting Hispanic Medicare beneficiaries

OBJECTIVE: To compare the utilization of total hip replacement (THR) between Hispanic persons and non-Hispanic persons in a sample with health insurance. RESEARCH DESIGN: Case-control study using Medicare claims data. PATIENTS: The cases were Medicare beneficiaries from Arizona, Illinois, New Mexico, or Texas who underwent a primary THR. The controls were Medicare beneficiaries who did not receive a THR, matched by age, sex, and county of residence. MEASURES: Beneficiary surnames and the race indicator in Medicare records were used to classify beneficiaries' probability of being Hispanic. Conditional logistic regression was used to estimate the odds of receiving of THR, adjusting for Medicaid eligibility. RESULTS: Six thousand four hundred thirty-seven recipients of a primary THR were matched to 12,874 controls. According to the Medicare race indicator, 1% of recipients of THR and 3.3% of controls were Hispanic (P < or =0.001). The odds of THR decreased as the probability of Hispanic ethnicity increased, from an odds ratio (OR) of 1.00 among beneficiaries with non-Hispanic surnames, to an OR of 0.36 among those with heavily Hispanic surnames (95% CI, 0.31, 0.43). Poverty, as reflected by eligibility for Medicaid, did not modify the low odds of THR among Hispanic persons (OR, 0.25 among Medicaid-eligible Hispanic persons; 95% CI, 0.19, 0.33; and OR, 0.30 among Hispanic persons not Medicaid eligible; 95% CI, 0.24, 0.38). CONCLUSION: Hispanic persons with Medicare receive THR at lower rates than do non-Hispanic persons. Because Medicare covers THR, our findings suggest that under utilization of THR by Hispanic persons cannot be attributed to lack of health insurance alone.     

Portal vein thrombosis: an emergency solution for blood flow in liver transplantation

Recipient portal vein thrombosis in liver transplantation is a contingency that increases surgical difficulty as well as patient morbidity and mortality. The aim of this paper is to demonstrate a surgical technique for reconstruction of portal blood flow in emergency situations of portal vein thrombosis with inadequate blood flow and a poor vascular bed for re-vascularization.     

Epidemiology of inhibitors and current treatment strategies

The development of inhibitors is currently one of the most serious complications in the treatment of hemophilic children. Prospective studies of previously untreated patients (PUP) showed that up to 52% of patients with severe hemophilia A developed inhibitors during the first 50 exposure days (ED) (>100 for outliers). Inhibitor development is influenced by the type of hemophilia, the severity and the type of mutation. No significant differences in inhibitor incidence were found in prospective studies conducted with plasma-derived or recombinant products. However, no comparative study has been finished yet. A still ongoing prospective, multi-center PUP-study initiated by the German, Austrian and the Swiss Society of Thrombosis and Hemostasis Research (GTH) foresees the direct comparison of different types of concentrates with regard to inhibitor development. Preliminary results (update February 2002) show a slightly higher inhibitor development (p=0.08) in severely affected hemophilia A patients treated with recombinant factor (F) VIII concentrates. However, the groups are very small and statistically reliable statements cannot be made at the moment. In case of inhibitor development rapid inhibitor elimination and immune tolerance induction (ITI) is the preferred way to reduce the high risk of bleeding episodes. In this respect, various therapeutic regimens, such as the administration of high doses of FVIII twice daily (Bonn protocol), or lower doses three times weekly (van Creveld protocol), have been attempted. Elimination of inhibitors from plasma by immune adsorption followed by immune suppression (Malm? protocol) has also been used. The influence of the type of concentrate used for ITI has never been investigated comparatively. A longitudinal study of ITI at our center showed a significantly decreased success rate since the introduction of high purity plasma derived and recombinant FVIII products using the Bonn protocol. In inhibitor patients who showed an unsatisfactory response to treatment with FVIII concentrates with very little or no VWF the change to concentrates containing high amounts of von Willebrand factor (VWF) increased success rates up to 90%. These observations raise the question of whether VWF plays an important role in the induction of immune tolerance.