Involvement of IL-1beta in acute stress-induced worsening of cerebral ischaemia in rats.

Stress is known to be one of the risk factors of stroke. Most of the knowledge on the effects of stress on cerebrovascular disease in humans is restricted to catecholamines and glucocorticoids effects on blood pressure and/or development of atherosclerosis. However, few experimental studies have examined the possible mechanisms by which stress may affect stroke outcome. We have used an acute stress protocol consisting of the exposure of male Fischer rats to an acute, single exposure immobilisation protocol (6 h) prior to permanent middle cerebral artery occlusion (MCAO), and we have found that stress worsens behavioural and neurological outcomes and increased infarct size after MCAO. The possible regulatory role of the TNFalpha and IL-1beta was studied by looking at the release of these cytokines in brain. The results of the present study showed an increase in IL-1beta release in cerebral cortex after exposure to acute stress. Brain levels of IL-1beta are also higher in previously stressed MCAO rats than in MCAO animals without stress. Pharmacological blockade of IL-1beta with an antibody anti-IL-1beta led to a decrease in the infarct size as well as in neurological and behavioural deficits after MCAO. In summary, our results indicate that IL-1beta, but not TNFalpha, accounts at least partly for the worsening of MCAO consequences in brain of rats exposed to acute stress.     

Delayed Keloid Lesion After Endoscopic Surgery of the Achilles Tendon

A case history of a 32-year-old female Olympic pole vaulter is reported. Two months after endoscopic surgery for chronic Achilles tendinopathy, she developed a keloid lesion on the hindfoot area. She was treated with corticosteroids, topical and intralesional injections. A satisfactory result was obtained, and the athlete was able to resume her competitive activity at 5 months after surgery. Keloid pathogenesis, treatment, and prevention are briefly discussed.     

Excellent results of cardiac surgery in patients with previous liver transplantation.

Cardiovascular diseases requiring surgical therapy in patients with prior liver transplantation are rare. Little is known about the outcome of patients with liver allograft undergoing cardiac surgery. Herein we report our experience in this patient population with an emphasis on operative outcomes and mid-term survival. Between January 1998 and December 2004, 12 patients (mean +/- standard deviation age 68 +/- 9 years, 7 [58%] male) with previous liver transplantation who underwent cardiac surgery were identified. Main outcome measures were hospital mortality, postoperative complications, allograft function, and long-term survival. There was no in-hospital mortality. Three major complications (25%) occurred, including 1 each (8%) of respiratory failure, renal failure, and biliary leakage. All complications were resolved by the time of discharge. Allograft dysfunction determined by an increase of liver function parameters was noticed in 4 (33%) and recovered before discharge. The average length of stay in intensive care unit was 72 +/- 45 hours, and the mean length of stay in hospital was 22 +/- 17 days. One- and 5-year survival was 91% +/- 8% and 67% +/- 14%, respectively. Cardiac surgery can be performed safely in liver transplant recipients with extremely low mortality and acceptable morbidities. Allograft dysfunction is a common finding, but it is transient, with early functional recovery. Five-year survival of liver recipients undergoing cardiac procedures is similar to that of the general population undergoing cardiac surgery. Our data suggest that these patients should be considered for cardiac surgery in reference centers with expertise in complex cardiac procedures and perioperative management of these highly specific patients.     

Seven DNA polymorphisms in the LDL receptor gene: application to the study of familial hypercholesterolemia in Spain

We have performed restriction fragment length polymorphism (RFLP) analysis at the low density lipoprotein receptor (LDLR) locus in order to investigate the molecular genetics of familial hypercholesterolemia (FH) in Spain. Firstly, a sample of 50 unrelated patients with a clinical diagnosis of FH was screened for the presence of major rearrangements at this locus by Southern blot analysis of Bgt II digested genomic DNA. Four different mutations were detected, accounting for 8% of the mutant alleles in the Spanish FH sample. Then, we determined the relative allele frequency and estimated linkage disequilibrium between seven RFLPs of the LDLR gene in the remaining 46 FH patients and in 61 normolipidemic controls. Hindi, Avail, Pvu II, Msp I, and Nco I are the most polymorphic sites with individual PIC values higher than 0.28, whereas the Taq I and Stu I sites display low levels of polymorphism. The usefulness of the seven RFLPs to confirm a clinical diagnosis of FH was investigated in 15 FH-families, consisting of 118 individuals, in whom the presence of Familial Defective Apolipoprotein B-100 (FDB) due to the apoB₃₅₀₀ mutation was excluded. Independent haplotypes were constructed for 71 chromosomes: 15 FH and 56 control haplotypes. A total of 14 different haplotypes was found. In 12 families, clinical diagnosis of FH was confirmed by cosegregation analysis, which makes these RFLPs useful for studying the inheritance of the LDLR gene in 80% of Spanish families with FH. Comparison of haplotypes found in the Spanish sample with those found in Swiss and Norwegians suggests heterogeneity of haplotypes among European populations.     

Liver Transplant Recipients Older Than 60 Years Have Lower Survival and Higher Incidence of Malignancy

Older age is not considered a contraindication for liver transplantation, but age-related morbidity may be a cause of mortality. Survival and the incidence of the main post-transplant complications were assessed in 111 adult liver transplant recipients. They were divided in two groups according to their age (patients younger than 60 years, n=54; patients older than 60 years, n=57) and both groups were compared. Older patients were more frequently transplanted for hepatitis C (p= 0.03) and hepatocellular carcinoma (p= 0.05) and their liver disease was less advanced (Child-Pugh and MELD scores were significantly lower; p=0.004 and p=0.05, respectively). After transplantation, older patients had a significantly lower survival (p=0.02). Higher age was independently associated with mortality (hazard ratio for each 10-year increase: 2.1; 95% confidence interval: 1.1- 4.0; p=0.02). The incidence of de novo neoplasia and nonskin neoplasia were higher in older patients (p=0.02 and p =0.007, respectively). Malignancy was the cause of death in one patient younger than 60 years and in 12 patients older than 60 years (p =0.002). In multivariate analysis, a higher age and smoking were independently associated with a higher risk of dying of de novo neoplasia. In conclusion, older liver transplant recipients have a significantly lower survival than younger patients. Malignancy is responsible for this decreased survival.