Abnormal liver function tests associated with severe rhabdomyolysis

Rhabdomyolysis is a syndrome of skeletal muscle injury with release of cellular constituents such as potassium,phosphate,urate and intracellular proteins such as myoglobin into the circulation,which may cause complications including acute kidney injury,electrolyte disturbance and cardiac instability.Abnormal liver function tests are frequently observed in cases of severe rhabdomyolysis.Typically,there is an increase in serum aminotransferases,namely aspartate aminotransferase and alanine aminotransferase.This raises the question of liver injury and often triggers a pathway of investigation which may lead to a liver biopsy.However,muscle can also be a source of the increased aminotransferase activity.This review discusses the dilemma of finding abnormal liver function tests in the setting of muscle injury and the potential implications of such an association.It delves into some of the clinical and experimental evidence for correlating muscle injury to raised aminotransferases,and discusses pathophysiological mechanisms such as oxidative stress which may cause actual liver injury.Serum aminotransferases lack tissue specificity to allow clinicians to distinguish primary liver injury from muscle injury.This review also explores potential approaches to improve the accuracy of our diagnostic tools,so that excessive or unnecessary liver investigations can be avoided.     

Outcomes of Donor Evaluations for Adult-to-Adult Right Hepatic Lobe Living Donor Liver Transplantation

The purpose of this study is to determine the role of liver biopsy and outcome of patients undergoing donor evaluation for adult-to-adult right hepatic lobe living donor liver transplantation (LDLT). Records of patients presenting for a comprehensive donor evaluation between 1997 and February 2005 were reviewed. Liver biopsy was performed only in patients with risk factors for abnormal histology. Two hundred and sixty patients underwent a comprehensive donor evaluation and 116 of 260 (45%) were suitable for donation, 14 of 260 (5.4%) did not complete evaluation and 130 of 260 (50%) were rejected. Four patients underwent unsuccessful hepatectomy surgery due to discovery of intraoperative abnormalities. Between 1997 and 2001, the acceptance rate of donor candidates (63%) was higher than 2002-2005 (36%), p < 0.0001. Sixty-six of the 150 eligible patients (44%) fulfilled criteria for liver biopsy and 28 of 66 (42%) had an abnormal finding. Less than half of the patients undergoing donor evaluation were suitable donors and the donor acceptance rate has declined over time. A large proportion of the patients undergoing liver biopsy have abnormal findings. Our evaluation process failed to identify 4 of 103 who had aborted donor surgeries.     

Responses of CDKs and p53 in Delayed Ischemic Neuronal Death

Stroke is a debilitating disease that affects millions each year.While in many cases cerebral ischemic in jury can be limited by effectivw resuscitation or thrombolytic treatment,the injured neurons wither in a process known as delayed neuronal death(DND).Mounting evidence indicates that DND is not simply necrosis played out in slow motion but apoptosis is triggered.Of particular interest are two groups of signal proteins that participate in apoptosis-cyclin dependent kinases(CDKs) and p53-among a myriad of signaling events after an ischemic insult.Recent investigations have shown that CDKs,a family of enzymes initially known for their role in cell cycle regulation,are activated in injured neurons in DND.As for p53,new reports suggest that its up-regulation may represent a failed attempt to rescue in jured neurons,although its up-regulation was previously considered an indication of apoptosis.These observations thus rekindle an old quest to identify new neuroprotective targets to minimize the stroke damage.In this review,the author will examine the evidence that indicates the participation of CDKs and p53 in DND and then introduce pre-clinical data to explore CDK inhibition as a potential neuroprotective target.Finally,using CDK inhibition as an example,this paper will discuss the pertinent criteria for a viable neuroprotective strategy for ischemic in jury.     

The effect of bone drilling on pain in gonarthrosis

Summary Seventy-seven patients with mild to moderate gonarthrosis of the knee were treated by subchondral bone drilling, and followed for from 2 to 7 years. Patients with generalised arthrosis benefited more than those with unicompartmental involvement. Pain, assessed by a visual analogue scale, was significantly reduced compared with a control group of 16 patients who had a diagnostic arthroscopy only. Drilling is a safe procedure with few complications and can be used in patients when more extensive surgery is not yet indicated or possible.

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Résumé Vingt-sept cas d'arthrose légère ou modérée du genou, diagnostiqués par arthroscopie et traités par forage, ont été revus avec un recul moyen de 4 ans (de 2 à 7 ans). La douleur, évaluée selon la cotation VAS, était diminuée pendant 24 mois en moyenne (1 à 76) dans les deux tiers des cas. Les résultats étaient meilleurs chez les patients présentant une arthrose globale que chez ceux atteints d'une arthrose uni-compartimentale. Ils étaient obtenus aussi bien dans les cas douloureux au repos (n=39) que dans ceux douloureux lors de la mobilisation du genou (n=14). Les complications ont été exceptionnelles (n=1). La douleur était diminuée dans une proportion significativement supérieure dans les genoux traités par forage que dans un groupe de contrôle de 16 cas, n'ayant subi qu'une arthroscopie à visée diagnostique (p=0.006). Le forage est un procédé sûr, n'entraînant que de rares complications. Il est indiqué dans le traitement des douleurs du genou chez les patients ayant une arthrose légère ou modérée, lorsque des interventions plus importantes ne sont ni nécessaires, ni réalisables.

     

Arthroscopy of the knee in children and adolescents

A retrospective review was done of 69 children and adolescents (7-17 years old) who underwent 75 arthroscopies of the knee during a 5-year period. Girls were overrepresented (71%). Thirty-eight were children under the age of 16. Of 46 injuries, 34 (74%) happened during sports. Children and adolescents were divided into two age groups based on their presumed state of skeletal maturity (boys 9–15 and girls 7–14 in group I and boys 16–17 and girls 15–17 in group II); meniscal lesions were equally common in the two groups, whereas anterior cruciate ligament tears were more common in older children (NS). Eleven of 17 (65%) anterior cruciate ligament lesions were combined with other intra-articular pathology, most often meniscal tears (9/11). As in other studies, half of the prearthroscopic diagnoses were incorrect. A high frequency of incorrect prearthroscopic diagnoses and of combined lesions justifies arthroscopy as an important diagnostic tool in children and adolescents with a history of twisting knee injury or chronic nonspecific knee problems. Girls practising ball games seem to be especially prone to knee injuries leading to arthroscopy.     

Nontraumatic glenohumeral instability and coracoacromial impingement in swimmers

Competitive swimming is one of the most demanding and time-consuming sports. Swimmers at elite level practice 20–30 h per week. During 1 year's practice, the average top level swimmer performs more than 500,000 stroke revolutions per arm. These innumerable repetitions over many years of hard training together with an increasing muscular imbalance around the shoulder girdle seem to be the main etiological factors in the development of the overuse syndrome swimmer's shoulder. Shoulder pain in swimmers has in general been regarded as synonymous with coracoacromial impingement, i.e. anterior shoulder pain due to rotator cuff tendinitis, but new knowledge suggests that a concomitant glenohumeral instability plays an additional role. The diagnostic complexity of the problem is as challenging as the search for the gold standard of treatment. The condition should ideally be diagnosed as early as possible, and intensive functional rehabilitation of the shoulder girdle including the scapular muscles should be started in order to restore muscle balance. The surgical possibilities include subacromial decompression in cases of purely mechanical impingement. If a painful glenohumeral instability persists after intensive functional rehabilitation, anterior capsulolabral reconstruction can be performed. Still, however, short- and long-term results show that surgery is less successful in elite athletes involved in overhead sports. Prevention protocols include education of coaches in primary injury prophylaxis and the institution of resistance strength training in prepubescent swimmers. Emphasis should be made to improve muscular balance around the glenohumeral and scapulothoracic joints.     

Wogonin inhibits osteoclast formation induced by lipopolysaccharide

To evaluate the inhibitory activity of wogonin against lipopolysaccharide (LPS)-induced bone resorption, we investigated the effect of wogonin on osteoclastogenesis induced by LPS. Wogonin inhibited LPS-induced osteoclastogenesis in co-cultures of mouse calvaria-derived osteoblasts and bone marrow-derived pre-osteoclasts. Wogonin also suppressed osteoclastogenesis in LPS-injected mouse calvaria. In osteoblasts, the upregulation of receptor activator of nuclear factor-κB (RANKL) expression and the downregulation of osteoprotegerin (OPG) expression by LPS were inhibited by wogonin. Wogonin and NS-398, a COX-2 inhibitor, suppressed LPS-stimulated PGE₂ production in osteoblasts. NS-398 inhibited the effect of LPS on RANKL and OPG expression in osteoblasts. These results suggest that wogonin acts as an inhibitor of LPS-induced osteoclastogenesis through downregulation of RANKL and upregulation of OPG expression via blockage of PGE₂ production. Based on these results, wogonin has potential for use as a therapeutic agent in bacteria-induced bone resorption. Copyright © 2009 John Wiley & Sons, Ltd.     

Auditory event-related magnetic fields in a tone-duration discrimination task. Source localization for the mismatch field and for a new component M2"

Auditory event related magnetic fields were measured using an odd-ball paradigm in which the rare event was a tone of short duration, D2, and the frequent one a tone of longer duration, D1. The subjects were required to attend to and count the number of rare stimuli. In the average across target stimuli a mismatch field (MMF) occurs and the dependence of the MMF, especially its latency, on the tone duration D2 is examined in detail. The location of an equivalent current dipole for the MMF-source is found and turns out to be at variance with earlier results. In addition to the MMF we propose a new component, here called MMF, which in time overlaps the magnetic equivalent of the P200 signal and which has a source location (equivalent current dipole) lying rather close to the MMF-source. The two sources are, however, active at latencies differing by a time equal to D2. We speculate that MMF indicates the onset of the process: "evaluation of tone-duration" while the MMF indicates the end of this process.