Human leukocyte antigen and adult living-donor liver transplantation outcomes: an analysis of the organ procurement and transplantation network database.

Human leukocyte antigen (HLA) compatibility has no clinically significant impact in cadaveric liver transplantation. Less is known regarding living-donor liver transplantation (LDLT). Our prior analysis of the Organ Procurement and Transplantation Network (OPTN) database suggested a higher graft failure rate in patients who underwent LDLT from donors with close HLA match. We further investigated the effect of HLA-A, -B, and -DR matching on 5-yr graft survival in adult LDLT by analyzing OPTN data regarding adult LDLT performed between 1998 and 2005. We evaluated associations between 5-yr graft survival and total, locus-specific, and haplotype match levels. Separate analyses were conducted for recipients with autoimmune (fulminant autoimmune hepatitis, cirrhosis secondary to autoimmune hepatitis, primary biliary cirrhosis, primary sclerosing cholangitis) or nonautoimmune liver disease. Multivariable Cox proportional hazard models were used to evaluate interactions and adjust for potential confounders. Among 631 patients with available donor/recipient HLA data, the degree of HLA match had no significant effect on 5-yr graft survival, even when analyzed separately in recipients with autoimmune vs. nonautoimmune liver disease. To be able to include all 1,838 adult LDLTs, we considered a first-degree related donor as substitute for a close HLA match. We found no difference in graft survival in related vs. unrelated pairs. In conclusion, our results show no detrimental impact of close HLA matching on graft survival in adult LDLT, including in recipients with underlying autoimmune liver disease.     

Association between the HOXA1 A218G polymorphism and increased head circumference in patients with autism.

BACKGROUND: The HOXA1 gene plays a major role in brainstem and cranial morphogenesis. The G allele of the HOXA1 A218G polymorphism has been previously found associated with autism. METHODS: We performed case-control and family-based association analyses, contrasting 127 autistic patients with 174 ethnically matched controls, and assessing for allelic transmission disequilibrium in 189 complete trios. RESULTS: A, and not G, alleles were associated with autism using both case-control (chi(2) = 8.96 and 5.71, 1 df, p <.005 and <.025 for genotypes and alleles, respectively), and family-based (transmission/disequilibrium test chi(2) = 8.80, 1 df, p <.005) association analyses. The head circumference of 31 patients carrying one or two copies of the G allele displayed significantly larger median values (95.0th vs. 82.5th percentile, p <.05) and dramatically reduced interindividual variability (p <.0001), compared with 166 patients carrying the A/A genotype. CONCLUSIONS: The HOXA1 A218G polymorphism explains approximately 5% of the variance in the head circumference of autistic patients and represents to our knowledge the first known gene variant providing sizable contributions to cranial morphology. The disease specificity of this finding is currently being investigated. Nonreplications in genetic linkage/association studies could partly stem from the dyshomogeneous distribution of an endophenotype morphologically defined by cranial circumference.     

Antiplatelet and antithrombotic activities of essential oil from wild Ocotea quixos (Lam.) Kosterm. (Lauraceae) calices from Amazonian Ecuador.

Ocotea quixos essential oil was shown to possess significant inhibitory activity of platelet aggregation and clot retraction in rodent plasma. This study is aimed at fully characterizing the antiplatelet activity of the whole essential oil and its main components trans-cinnamaldehyde and methyl cinnamate also in human plasma, at investigating the mechanism underlying such activity and at evaluating the potential antithrombotic activity of subacute treatment of mice with Ocotea essential oil. In vitro Ocotea essential oil and trans-cinnamaldehyde inhibited arachidonic acid-, U46619-, ADP-, phorbol12-myristate13-alcetate-, collagen-induced platelet aggregation and thrombin-induced clot retraction in human and rodent plasma; Ocotea oil and trans-cinnamaldehyde competitively antagonized contractions induced by thromboxane A2 receptor agonist U46619 in rat isolated aortic ring (K(B) = 18 and 3.2 microg ml(-1), respectively). In vivo Ocotea oil, orally administered in a subacute treatment (30-100 mg kg(-1) day(-1) for 5 days) to mice, prevented acute thrombosis induced by collagen-epinephrine intravenous injection. This antithrombotic activity was not accompanied by pro-haemorragic side effect, as detected by the inactivity in bleeding test, thus showing a favourable safety profile compared to the conventional antiplatelet agent, acetylsalicylic acid. Present findings indicate that Ocotea essential oil possesses potent and safe antithrombotic activity attributable to its antiplatelet and vasorelaxant effects. The main constituent trans-cinnamaldehyde seems to be the primary responsible for this activity through a putative mechanism involving the inhibition of thromboxane A2 receptors.     

Changing patterns of abnormal vascular wall F-18 fluorodeoxyglucose uptake on follow-up PET/CT studies.

BACKGROUND: Fluorine 18 fluorodeoxyglucose (FDG) uptake may be increased in atherosclerotic plaques in asymptomatic patients. Repeat positron emission tomography (PET)/computed tomography (CT) studies were assessed for changes in patterns of FDG uptake and CT calcifications. METHODS AND RESULTS: Fifty consecutive cancer patients (mean age, 68 +/- 8 years) had repeat PET/CT studies 8 to 26 months apart. PET, CT, and PET/CT images were retrospectively evaluated for vascular wall abnormalities and for interval changes in the thoracic and abdominal aortas, as well as in carotid and iliac arteries, classified as PET+/CT+, PET+/CT-, and PET-/CT+. There were 485 abnormal sites in the first study and 495 in the second. CT calcifications were found in 46 patients (92%) in the first study and in 47 (94%) in the second. Vascular wall FDG uptake was found in both studies in 37 patients (74%). The pattern changed in 57 of 119 PET+ sites (48%) in the second study compared with 15 of 366 PET- sites (4%) (P < .0001). In the second study new PET+ sites were observed in 36 of 111 sites (32%) versus new PET-/CT+ sites in 19 of 384 sites (5%) (P < .0001). CONCLUSIONS: Changes in vascular FDG activity and CT calcifications can be assessed by repeat PET/CT. FDG-avid foci may represent a dynamic process, transient inflammation, whereas CT calcifications may indicate stable atherosclerosis. These preliminary results support the need for further research.     

Chronic parasite infection in mice induces brain granulomas and differentially alters brain nerve growth factor levels and thermal responses in paws

Schistosoma mansoni infection, both in humans and in animal models, is known to induce granulomas in the liver and intestine. It has also been reported that in humans the eggs of this parasite can reach the brain, causing psychiatric and neuropathological disorders. Whether this also occurs in rodents is unknown. To answer this question, mice were infected with this parasite and the central nervous system (CNS) examined at various time intervals. The results show that schistosomiasis induced granulomas in several regions of the CNS and increased nerve growth factor (NGF) levels in the cortex, hypothalamus and brain stem, but not in the hippocampus. The infection also caused paw hyperalgesia, as determined by the hot-plate test, and a local increase in NGF, but not in substance P. These findings indicate that the murine model of infection can be used for studying mechanisms leading to human neuroschistosomiasis and suggest that the neuropathological disorders and the sensory deficits observed in human schistosomiasis are associated with impaired levels of NGF in the peripheral and central nervous system. Received: 18 January 1996 / Revised, accepted: 16 April 1996     

Clinical epidemiology and survival of progressive multifocal leukoencephalopathy in the era of highly active antiretroviral therapy: Data from the Italian Registry Investigative Neuro AIDS (IRINA)

Human immunodeficiency virus (HIV)-associated progressive multifocal leukoencephalopathy (PML) remains a relevant clinical problem even in the era of highly active antiretroviral therapy (HAART). Aims of the study were to analyze clinical and treatment-related features and the survival probability of PML patients observed within the Italian Registry Investigative Neuro AIDS (IRINA) during a 29-month period of HAART. Intravenous drug use, the presence of focal signs, and the involvement of white matter at neuroradiology increased the risk of having PML. A reduced probability of PML was observed when meningeal signs were reported. Patients starting HAART at PML diagnosis and previously naïve for antiretrovirals showed significantly higher 1-year probability of survival (.58), compared to those continuing HAART (.24), or never receiving HAART (.00). Higher CD4 cell count were associated with a higher survival probability (.45). At multivariate analysis, a younger age, higher CD4, starting HAART at PML diagnosis, the absence of previous acquired immunodeficiency syndrome (AIDS)-defining events, and the absence of a severe neurologic impairment were all associated with a reduced hazard of death. The use of cidofovir showed a trend towards a reduced risk of death.     

Dynamic contrast-enhanced ultrasound with carbon dioxide microbubbles as adjunct to arteriography of liver tumors

Purpose The goal of the study is to evaluate utility of contrast enhanced ultrasound (US) with carbon dioxide microbubbles in evaluation of hepatic lesions.Methods Twenty eight patients with single or multiple t hepatic lesions (11 hepatocellular carcinoma, 8 hemangiomas, 5 metastases, 1 adenoma, 1 focal nodular hyperplasia, 2 regenerative nodules) were examined. US exam was performed during intraarterial injection of 10 ml of CO₂ through the same catheter employed for liver arteriography. The US exam was videotaped in its salient phases. Characteristics of enhancement were evaluated and correlated with histological findings or patient follow up.Results Sonographic angiography clearly demonstrated vascularization of the lesions. Hepatocellular carcinoma, hemangioma, metastases, focal nodular hyperplasia, and regenerative nodules had very characteristic patterns. The injection of CO₂ allowed detection of small additional nodules.Conclusion Sonographic angiography can improve characterization and staging of hepatic tumors. Low cost and the simplicity of the technique should encourage further experimentation.     

Comorbidities of migraine: a user-friendly overview

Comorbidity of migraine is important from a number of different perspectives. Co-occurrence of different diseases may complicate diagnosis as a high degree of symptomatic overlap may occur among conditions associated with migraine. Furthermore, comorbidity has also important implications for treatment. The commonest comorbidities of migraine are represented by psychiatric disorders, epilepsy, tremor, stroke, and cardiovascular abnormalities.