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.     

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 prevalence of chromium allergy in Denmark is currently increasing as a result of leather exposure

Background Chromium allergy has traditionally been caused by occupational skin contact with cement. In 1983, Danish legislation made the addition of ferrous sulphate compulsory in cement to reduce the water‐soluble chromium content to not more than 2 ppm. An effect from this intervention has previously been demonstrated among Danish construction workers. Objectives To investigate the development of chromium allergy among patients with dermatitis tested between 1985 and 2007 in Denmark. Furthermore, to determine causative exposures in patients with chromium allergy. Patients and methods A retrospective analysis of patch test data was performed (n = 16 228) and charts from patients with chromium allergy were reviewed. Comparisons were made using a χ² test. Logistic regression analyses were used to test for associations. Results The prevalence of chromium allergy decreased significantly from 3·6% in 1985 to 1% in 1995 (P_trend < 0·001) but increased to 3·3% in 2007 (P_trend < 0·001). The frequency of clinically relevant cement exposure decreased significantly among patients with chromium allergy from 12·7% in 1989–1994 to 3·0% (P < 0·01) in 1995–2007, whereas the frequency of relevant leather exposure increased significantly from 24·1% during 1989–1994 to 45·5% during 1995–2007 (P < 0·02). Conclusions Chromium allergy is currently increasing in Denmark due to leather exposure.     

Lung function development in the first 2 yr of life is independent of allergic diseases by 2 yr

The aim of the study was to assess if lung function at birth predicts lung function at 2 yr and secondly, if lung function development was influenced by the common phenotypes of recurrent bronchial obstruction (rBO) or atopic eczema (AE) by 2 yr. Lung function was assessed at birth (n = 802) and at 2 yr within the prospective birth cohort study 'the Environment and Childhood Asthma Study' in Oslo. The 135 children with lung function measured at birth by tidal flow volume (TFV) loops and passive respiratory mechanics, who were included in a nested case-control study were reinvestigated at 2 yr with clinical examination, TFV loops (n = 90) (mean age 26.6 (3.7 s.d.) months), skin prick test and parental interview. Children were categorized into quartiles (lower, middle two, upper) according to time to peak tidal expiratory flow/total expiratory time (t(PTEF)/t(E)) at birth as well as clinical phenotype based on the presence of rBO and/or AE (ever) by 2 yr. The observed reduction in mean t(PTEF)/t(E) from birth to 2 yr within the quartiles, were not significantly different after controlling for 'regression to the mean'. t(PTEF)/t(E) at birth correlated significantly with t(PTEF)/t(E) at 2 yr, (r = 0.475, p < 0.001). Children with both rBO and AE by 2 yr had significantly lower t(PTEF)/t(E) at 2 yr (p = 0.002) and at birth (p = 0.027), compared with children with no rBO or AE. Clinical phenotype at 2 yr did not influence the change in t(PTEF)/t(E) from birth to 2 yr. This study demonstrates a clear tracking of lung function from birth, not influenced by rBO or AE by 2 yr.     

Soluble CD14 at 2 yr of age: Gender-related effects of tobacco smoke exposure, recurrent infections and atopic diseases

The endotoxin receptor soluble CD14 (sCD14) has been implicated in the 'hygiene hypothesis' suggesting reduced allergic sensitization with bacterial stimulation. However, the relationship between early life sCD14 and allergic diseases is conflicting. We aimed to investigate whether possible risk factors for allergic diseases were associated with sCD14 levels at 2 yr of age. In the nested case-control study of the birth cohort studies 'Environment and Childhood Asthma study in Oslo' 411 children selected with recurrent bronchial obstruction (rBO) (n=241) and no bronchial obstruction (n=170) by 2 yr were investigated with skin prick test and structured parental interview at age 2 yr. Exposure to tobacco smoke, pets and infections was recorded semi-annually by questionnaires (0-2 yr). The sCD14 was analysed from frozen, stored serum by ELISA technique. Regression analyses were performed in all subjects with complete data (n=406, 180 girls), and in girls and in boys separately. Mean sCD14 (ng/ml) was significantly higher among girls 2035 (1973-2096) vs. 1947 (1890-2004) (boys). The sCD14 was significantly reduced among girls exposed to antenatal maternal smoking and with parental asthma, after adjusting for age, parental rhino-conjunctivitis, pet keeping and childhood infections. Recurrent otitis media (OM) increased and common colds significantly decreased sCD14 levels in girls. Boys with atopic dermatitis and rBO had reduced sCD14. Pet exposure was not significantly associated with sCD14. We report novel gender-related effects of sCD14 in early life and suggest that gender, tobacco smoke exposure, age and middle ear disease in particular should be accounted for when assessing the role of sCD14 in childhood allergic diseases.     

Evaluation of regional cerebral circulation based on absolute mean transit times in radionuclide cerebral angiography

In radionuclide cerebral angiography (RCA) the analysis of the activity-time curves recorded over the hemispheres following an intravenous bolus injection of a radioactive indicator permits the evaluation of absolute cerebral mean transit times (MTTcb). The inverse of MTTcb is an index of cerebral blood flow. The bolus parts of the cerebral activity curves were fitted with gamma-variate functions. The duration of the injection bolus and its subsequent dispersion through the cardiopulmonary circulation were corrected for using the activity curve over the aortic arch. In a control material of 52 subjects MTTcb was uncorrelated with age and equal to 3.2 +/- 0.67 s (means +/- 1 SEE) for the 37 subjects younger than 60. For the fifteen subjects older than 60, mean MTTcb showed a steep increase with age. The results were in close agreement with those obtained by other researchers using either correction of cerebral curves based on a physical flow model or direct injections into the internal carotid artery. Comparison of RCA with x-ray carotid angiography in 12 subjects was satisfactory. Repeated RCA examinations in nine subjects a few days apart yielded a reproducibility of 0.7 s for MTTcb. The RCA is non-invasive, rapid, easy to perform and without risk for the patient. The RCA is recommended for quantitative evaluation of major alterations in cerebral perfusion.     

Expression of growth-associated proteins (GAPs) in injured sensory axons of frogs acclimatized to 15 °C and 25 °C

Labelled proteins conveyed by fast axonal transport into the sensory axons of frog sciatic nerve following axotomy have been studied by 2D gel electrophoresis. Previous work showed that in frogs acclimatized to 25 °C a cell body reaction occurs, along with regeneration of axons to their targets. In contrast, frogs acclimatized to 15 °C showed no cell body reaction and though regeneration began, it stalled after approximately 35 days. We found that axotomy at 25 °C was followed by an increase in transport of specific labelled proteins corresponding to growth-associated proteins (GAPs) identified in other regenerating systems. Surprisingly, axotomy at 15 °C also induced a similar increase, though with a slower onset, so that the highest levels of expression of GAPs occurred during the time when the axons had stalled. We conclude that sensory neurons in 15 °C frogs do detect that their axons have been injured, as shown by their ability to increase GAP synthesis. Slow and limited axonal growth is possible during a period when GAP synthesis is low compared to levels in rapidly regenerating nerves, but even when the ability to produce GAPs increases, this alone is not sufficient to sustain regeneration in the absence of other components of the cell body reaction to injury.