Psychosocial situation and physical health in 50 patients > 1 year after lung transplantation

BACKGROUND: Lung transplants have been performed worldwide since the early 1980s. While numerous studies have been published on somatic aspects after lung transplantation, there is considerably less information available on psychosocial aspects and on the correlation between the physical and the psychosocial state of health after transplantation. METHODS: Between 1992 and 2002, 125 patients underwent lung transplantation at University Hospital Zurich. To be included into the study, patients had to have received a lung transplant > 12 months previously and to have good knowledge of the German or Italian languages. With the aid of standardized questionnaires, psychosocial variables such as levels of anxiety and depression, self-esteem, and social support were determined. In addition, self-assessments of physical and psychological health were obtained. The medical data included information on FEV1, complications such as pulmonary infections, acute or chronic allograft rejection, and assessment of the patient's physical and psychological health by the treating doctors. RESULTS: The overall degree of anxiety and depression of the lung transplant recipients was comparable to standard samples of an average population. However, male lung transplant recipients were significantly more depressed than female recipients. Self-esteem was higher than in clinical comparison samples. Preceding pulmonary complications had long-lasting effects on the level of anxiety, whereas nonpulmonary complications did not have such an effect. CONCLUSIONS: Overall, the psychological well-being of patients after lung transplantation is similar to the normal population. Subgroups of patients with increased psychological distress have been identified.     

Sinusoidal endothelial cell and hepatocyte death following cold ischemia-warm reperfusion of the rat liver

Cold ischemia-warm reperfusion (CI-WR) injury of the liver is characterized by marked alterations of sinusoidal endothelial cells (SECs), whereas hepatocytes appear to be relatively unscathed. However, the time course and mechanism of cell death remain controversial: early versus late phenomenon, necrosis versus apoptosis? We describe the occurrence and nature of cell death after different periods of CI with University of Wisconsin (UW) solution and after different periods of WR in the isolated perfused rat liver model. After 24- and 42-hour CI (viable and nonviable livers, respectively), similar patterns of liver cell death were seen: SEC necrosis appeared early after WR (10 minutes) and remained stable for up to 120 minutes. After 30 minutes of WR, apoptosis increased progressively with WR length. Based on morphological criteria, apoptotic cells were mainly hepatocytes within liver plates or extruded in the sinusoidal lumen. In addition, only after 42-hour CI were large clusters of necrotic hepatocytes found in areas of congested sinusoids. In these same livers, the hepatic microcirculation, evaluated by means of the multiple-indicator dilution technique, revealed extracellular matrix disappearance with no-flow areas. In conclusion, different time courses and mechanisms of cell death occur in rat livers after CI-WR, with early SEC necrosis followed by delayed hepatocyte apoptosis. These processes do not appear to be of major importance in the mechanism of graft failure because they are similar under both nonlethal and lethal conditions; this is not the case for the loss of the extracellular matrix found only under lethal conditions and associated with hepatocyte necrosis.     

Do the recently modified pacemaker guidelines for neurocardiogenic syncope also apply to young patients? Analysis based on five-year follow-up of israeli soldiers with syncope and a positive tilt test

To assess the classification of neurocardiogenic syncope (NCS) as a IIA indication for pacemaker implantation in the recent American College of Cardiology/American Heart Association Task Force on Practice Guidelines/North American Society for Pacing and Electrophysiology guidelines, we performed chart reviews and follow-up interviews in a cohort of 45 consecutive young Israeli soldiers (age 18-24 years) with a history of syncope (mean of 9 prior syncopal episodes) and a positive tilt test treated with drug therapy. Asystole longer than 5 s during tilt testing occurred in 11 patients. Five years later, we found that only 2 patients were still taking medications, only 1 patient (2%) still reported frequent syncopal or near-syncopal episodes and 3 patients (7%) had rare symptoms (no more than one syncopal episode during the past 2 years), while the remaining 40 (89%) were symptom free off medications. Thus, NCS in young patients, even with prolonged asystole during tilt testing, a history of frequent syncopal episodes and other high- risk factors described in the guidelines, is often a self-limiting disorder, perhaps stress related or situational in nature; an overwhelming number of patients become asymptomatic and stop taking medications within 1-2 years. These patients do not require long-term therapy; thus, our data would suggest that the IIA pacing indication for NCS should be restricted to older patients.     

The complementary aggregation sites of fibrin investigated through examination of polymers of fibrinogen with fragment E

Fibrin polymerizes through the interaction of sites exposed by the thrombin-mediated cleavage of fibrinopeptides in the central E region of the protein and complementary sites near the ends of the molecules, open in the D regions of both fibrinogen and fibrin. A preparation of fragment E, containing the central domain and part of the coiled-coil regions of fibrin, was used in mixtures with fibrinogen in this electron microscopy study to investigate the formation of fibrillar structures. At short times, linearly ordered oligomers of fibrinogen were observed with an additional mass of E fragments at the end-to-end junctions. At later times, long flexible polymers made up of 30 or more fibrinogen and fragment E units, with a tendency for lateral aggregation and tangle formation, were seen. These single-stranded assemblies could be readily dissociated in dilute acetic acid into their fibrinogen and fragment E components. However, if the aggregates were treated with factor XIIIa so that all γ chains became ligated by N(γ-glutamyl)lysine linkages, the polymers could no longer be taken apart. Because the only γ chains in the preparation are present in the fibrinogen molecules interacting end-to-end, the findings show that the factor XIIIa-induced cross-linking of γ chains in the clotting of fibrinogen or fibrin must occur between molecules that are longitudinal (or end-to-end) rather than transverse (or half-staggered).     

Safety of allopurinol compared with other urate-lowering drugs in patients with gout: a systematic review and meta-analysis

Allopurinol is the most widely used urate-lowering drug (ULD). Together with efficacy and cost, safety is an aspect that helps taking clinical decisions. This systematic review analyzes allopurinol safety. The literature search was performed in MEDLINE, EMBASE, and the Cochrane Library (January 2014). Selection criteria: (a) patients >18, (b) gout by the ACR criteria or evidence of urate crystal in synovial fluid, (c) comparator (placebo or other ULD), and (d) RCTs, cohorts, or meta-analysis. Primary outcomes: rate of adverse events and death. The quality was assessed with the Jadad’s scale. A meta-analysis with fixed effects was performed. From 544 studies, seven met the eligibility criteria and were included. All RCT presented a low power for safety. All RCTs included a mixed population of patients with gout and hyperuricemia. Allopurinol (300 mg) was compared to febuxostat (40–240 mg) in five RCTs, to benzbromarone and probenecid in two RCTs, and to placebo in one. In the RCTs comparing allopurinol with benzbromarone and probenecid, the highest discontinuation rate was with probenecid (26 %), followed by allopurinol (11 %) and benzbromarone (4 %). The incidence of adverse events was similar between allopurinol (range 38.6–85) and febuxostat (range 41.8–80). Six patients on febuxostat and three on allopurinol died during the studies; no deaths were judged related to drug. The combined risk of adverse events was RR = 1.04 (95 % CI 0.98, 1.11). Allopurinol is a safe option, slightly better than other ULDs. The grade of evidence is high, but further research is needed to evaluate higher doses and long-term safety.