The MASTiFF panel—a versatile multiple-allele SNP test for forensics

International Journal of Legal Medicine - Forensic identification tests often need recourse to markers that can successfully type highly degraded DNA, and binary single nucleotide polymorphisms...     

Neuronal vacuolation in young Rottweiler dogs

Neuronal vacuolation, involving the cerebellar roof nuclei, Purkinje cells, selected nuclei of the brain stem, thalamus, Clarke’s column, anterior and posterior horns of the spinal cord, visceral autonomic ganglia and myenteric plexus, as well as axonal degeneration of the white matter of the brain stem, cerebellar pedunculi, dorsolateral columns of the spinal cord and ventral roots of the spinal cord, were observed in two young Rottweiler dogs which were clinically afflicted with hind limb weakness progressing to paraparesia, ataxia, intention tremor, and difficulty in swallowing and barking. The absence of modifications in Bcl-2 and Bax immunoreactivity, a lack of strong c-Jun/AP-1 (N) immunoreactivity in vacuolated cells, and the absence of DNA breaks, as seen with the method of in situ end-labeling of nuclear DNA fragmentation, all suggest that there is no involvement of the apoptotic pathway in vacuolated cells in this new neurodegenerative disorder. Received: 20 May 1998 / Revised, accepted: 13 July 1998     

Liver Transplant From Unexpected Donation After Circulatory Determination of Death Donors: A Challenge in Perioperative Management

Unexpected donation after circulatory determination of death (uDCD) liver transplantation is a complex procedure, in particular when it comes to perioperative recipient management. However, very little has been published to date regarding intraoperative and immediate postoperative care in this setting. Herein, we compare perioperative events in uDCD liver recipients with those of a matched group of donation after brain death liver recipients. We demonstrate that the former group of recipients suffers significantly greater hemodynamic instability and derangements in coagulation following graft reperfusion. Based on our experience, we recommend a proactive recipient management strategy in uDCD liver transplantation that involves early use of vasopressor support; maintaining adequate intraoperative levels of red cells, platelets, and fibrinogen; and routinely administering tranexamic acid before graft reperfusion.     

Foot-and-mouth disease vaccine potency testing in cattle using homologous and heterologous challenge strains: precision of the "Protection against Podal Generalisation" test

The level of protection conferred by foot-and-mouth disease (FMD) vaccines in primovaccinated animals primarily depends on the potency of the vaccine and the relatedness of the vaccine strain and circulating field isolate. The "Gold Standard" FMD vaccine potency test is the in vivo test performed in the target species. The objective of the study was to determine the precision of the in vivo "Protection against Podal Generalisation" (PPG) FMD vaccine potency test in cattle using homologous (vaccine quality control) and heterologous (vaccine matching) viral challenge. The overall level of protection induced by the A(24) Cruzeiro/Brazil/55 vaccine used in six homologous PPG tests was 88.5%. Vaccine accordance (VACC) and vaccine concordance (VCON) were estimated to be 75.9% and 73.7%, respectively. In four heterologous challenge PPG tests, the overall level of cross-protection induced by the A(24) Cruzeiro/Brazil/55 vaccine against A Argentina/2001 challenge was 26.6%, with VACC and VCON values of 65.7% and 59.2%, respectively. Results indicate that the homologous PPG test is more reliable than the European Pharmacopoeia potency test, but that a larger number of animals should be used in order to increase the test's statistical power. In this regard, indirect alternative tests for vaccine potency and vaccine matching merit consideration.     

Acral mutilation syndrome in a miniature pinscher

Acral mutilation syndrome (AMS) is a rare canine hereditary sensory neuropathy that results in progressive mutilation of the distal extremities and which has been reported only in German short-haired pointers, English pointers, English springer spaniels and French spaniels. The present report describes a case of AMS in an 18-month-old female miniature pinscher with progressive self-mutilation of the hind feet. The dog did not respond to any treatment and was humanely destroyed at the age of 30 months. Microscopical findings post mortem were restricted to the nervous system and were compatible with AMS. This is the first case of AMS described in a miniature pinscher. It is not known if the disease was the result of a point mutation in this particular dog or if the miniature pinscher breed will evolve to become a breed predisposed to AMS.     

Persistence of low platelet adhesiveness in von Willebrand disease during pregnancy

Platelet adhesiveness (PA) is a valuable measure of ex vivo platelet function. A low PA is a usual feature of von Willebrand disease (vWd). However, PA has rarely been measured during vWd pregnancies. The aim of this work was to observe the behaviour of PA in vWd pregnancies. PA was measured during pregnancy in 33 vWd patients. Intrapregnancy PA remained low without any significant variation compared with non-pregnancy values. Advanced gestation was not accompanied by any increase in PA in spite of the concomitant normalization showed by the other markers of vWd. A low intrapregnancy value was not predictive of an increased risk of bleeding at labour. A low PA could be the only clue for vWd during gestation warranting both a vigilant postpartum attitude and a thorough haemostatic evaluation after pregnancy.     

Assessment of addiction severity among ritual users of ayahuasca

Ayahuasca is a psychoactive beverage used for magico-religious purposes in the Amazon. Recently, Brazilian syncretic churches have helped spread the ritual use of ayahuasca abroad. This trend has raised concerns that regular use of this N,N-dimethyltryptamine-containing tea may lead to the medical and psychosocial problems typically associated with drugs of abuse. Here we assess potential drug abuse-related problems in regular ayahuasca users. Addiction severity was assessed using the Addiction Severity Index (ASI), and history of alcohol and illicit drug use was recorded. In Study 1, jungle-based ayahuasca users (n = 56) were compared vs. rural controls (n = 56). In Study 2, urban-based ayahuasca users (n = 71) were compared vs. urban controls (n = 59). Follow-up studies were conducted 1 year later. In both studies, ayahuasca users showed significantly lower scores than controls on the ASI Alcohol Use, and Psychiatric Status subscales. The jungle-based ayahuasca users showed a significantly higher frequency of previous illicit drug use but this had ceased at the time of examination, except for cannabis. At follow-up, abstinence from illicit drug use was maintained in both groups except for cannabis in Study 1. However, differences on ASI scores were still significant in the jungle-based group but not in the urban group. Despite continuing ayahuasca use, a time-dependent worsening was only observed in one subscale (Family/Social relationships) in Study 2. Overall, the ritual use of ayahuasca, as assessed with the ASI in currently active users, does not appear to be associated with the deleterious psychosocial effects typically caused by other drugs of abuse.     

High incidence of delayed graft function in HIV‐infected kidney transplant recipients

Kidney transplantation (KT) outcomes in human immunodeficiency virus (HIV)‐infected recipients are under continuous research. High incidence of early post‐transplant complications such as acute rejection has been observed. A multicenter study including HIV‐infected patients who underwent KT in Spain, from 2001 to 2011, was performed. The study population included 108 recipients, 36 HIV‐infected, and 72 matched HIV‐negative KT recipients. HIV‐infected recipients developed more delayed graft function (DGF) (52% vs. 21%, P < 0.001). One‐ and 3‐year graft survival was 91.6% and 86.2% in HIV‐infected patients, and 97.1% and 94.7% in HIV‐negative patients (P = 0.052). In two‐variate Cox analysis, HIV infection was not a predictor of graft loss after adjusting for time on dialysis, acute rejection, and DGF. Multivariate analysis for DGF revealed HIV‐positive status as independent risk factor. We analyzed the evolution of immunosuppressive and antiretroviral therapy (ART). In HIV‐infected patients tacrolimus trough levels were very high in the first week and significantly lower in the second week post‐transplant (P = 0.042). Post‐transplant ART was significantly changed: protease inhibitors use decreased (P = 0.034) and integrase inhibitor use increased (P < 0.001). DGF is another frequent early complication in HIV‐infected recipients that can affect graft survival. Strategies to prevent DGF and antiretroviral regimes with less drug interactions could improve outcomes.     

Fibronectin‐α4β1 Interactions in Hepatic Cold Ischemia and Reperfusion Injury: Regulation of MMP‐9 and MT1‐MMP via the p38 MAPK Pathway

Liver ischemia‐reperfusion injury (IRI) remains a challenging problem in clinical settings. The expression of fibronectin (FN) by endothelial cells is a prominent feature of the hepatic response to injury. Here we investigate the effects of the connecting segment‐1 (CS‐1) peptide therapy, which blocks FN‐α4β1 integrin leukocyte interactions, in a well‐established model of 24‐h cold liver IRI. CS‐1 peptides significantly inhibited leukocyte recruitment and local release of proinflammatory mediators (COX‐2, iNOS and TNF‐α), ameliorating liver IRI and improving recipient survival rate. CS1 therapy inhibited the phosphorylation of p38 MAPK, a kinase linked to inflammatory processes. Moreover, in addition to downregulating the expression of matrix metalloproteinase‐9 (MMP‐9) in hepatic IRI, CS‐1 peptide therapy depressed the expression of membrane type 1‐matrix metalloproteinase (MT1‐MMP/MMP‐14) by macrophages, a membrane‐tethered MMP important for focal matrix proteolysis. Inhibition of p38 MAPK activity, with its pharmacological antagonist SB203580, downregulated MMP‐9 and MT1‐MMP/MMP‐14 expressions by FN‐stimulated macrophages, suggesting that p38 MAPK kinase pathway controls FN‐mediated inductions of MMP‐9 and MT1‐MMP/MMP‐14. Hence, this study provides new insights on the role of FN in liver injury, which can potentially be applied to the development of new pharmacological strategies for the successful protection against hepatic IRI.     

Cost/efficacy clinical trial about the use of T-tube in cadaveric donor liver transplant: preliminary results

Biliary reconstruction is the most common cause of morbidity associated with orthotopic liver transplantation. Our objective was to assess the complications and hospital resources related to the use of a T-tube. MATERIAL AND METHODS: Among 95 liver transplants performed from October 2002 to November 2003, 84 patients were randomized to receive a T-tube or no T-tube. We analyzed all patients with a follow-up of at least of 3 months. RESULTS: Fifty-five transplants were analyzed with 8 months mean follow-up, including twenty eight with T-tube and twenty seven without a T-tube. No patient died during the follow-up. The overall rate of biliary complications was 45.4% (25/55) including 21/28 (75%) in the T-tube group and 4/27(14.8%) in the non-T-tube group (P < .0001). Complications related to T-tube extraction occurred in 48.2% (13/27), including 3 cholangitis and 10 leaks. The costs of hospital resources due to radiological studies were 5329 capital JE, Ukrainian for the T-tube group vs 5785 capital JE, Ukrainian for the non-T-tube group. The costs of hospital resources due to treatment were 28,280 capital JE, Ukrainian for the T-tube group vs 10,088 capital JE, Ukrainian for the non-T-tube group. CONCLUSIONS: Use of a T-tube during orthotopic liver transplantation does not seem justified. Biliary anastomosis stenting is followed by an increased incidence of complications, most of which are related to its use. Hospital stay, radiological studies, and cost of hospital resources are higher among the T-tube patients. Therefore its systematic use is not advisable.