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.     

Reaming versus non-reaming in medullary nailing: Interference with cortical circulation of the canine tibia

Summary Medullary nails have only been used with reluctance in the treatment of open fractures since reaming interferes with the cortical circulation. The technique of interlocking offers the interesting possibility of inserting a relatively stiff nail which does not necessarily require reaming. The effects of reaming prior to nail insertion upon the cortical circulation was investigated in the canine tibia. Intravital staining with procion red was used to trace areas of disturbed circulation. Nail insertion without reaming provided clear advantages for the bone's blood supply, while reaming disturbed perfusion in two-thirds of the cortical area and regionally extended through the entire thickness of the cortex. The disturbance without reaming was limited to the inner layer of the cortex and involved only one-third of the cortical cross-section.     

Treatment of defects of the long bones using distraction osteogenesis (Ilizarov) and intramedullary nailing. Theoretic principles, animal experiments, clinical relevance

For large shaft defects of tibia and femur, distraction-compression osteosynthesis (Ilizarov) provides an ideal autologous bone graft. Combination of this with an intramedullary interlocking nail instead of an external fixator could improve patient comfort, because transport with a small external device takes only one-third of the total fixation period. Using 21 adult female sheep we created standardized tibia shaft defects 20 mm (medium size) and 45 mm (large size) in length. The tibiae were stabilized with non-reamed intramedullary interlocking nails. Following corticotomy by chisel, segments were transported using subcutaneous traction wires with a screw as a fulcrum to maintain stationary skin exit points without soft tissue problems. The external traction devices were removed after 12 or 16 weeks. Animals were sacrificed after 12 or 24 weeks with medium-size defects, and after 16 or 32 weeks with large defects. We evaluated the results clinically, by standardized weekly X-rays and, after sacrifice, by quantitative computed tomography (QCT). No animals had to be excluded from the study. Despite primary destruction of the intramedullary circulation all distraction gaps were spanned with bone. X-Rays showed typical signs of good quality of distraction bone regeneration (narrow radiolucent zone in the middle of the regenerate, longitudinal structure), continuous calcification, and cortex formation. QCT cross sections showed completely circular bone regeneration with small and large defects. Bone regeneration was faster on the dorsal side, where more bone was formed than ventrally. Small defects can remain ventrally in the regenerate; these close secondarily.(ABSTRACT TRUNCATED AT 250 WORDS)     

Lyme disease: recommendations for diagnosis and treatment

The incidence and the endemic range of Lyme disease in the United States have increased steadily since the disease was originally recognized in Lyme, Connecticut, in 1975. Because of the varied clinical manifestations of this illness and the use of unstandardized serologic testing methods, diagnosis is often uncertain and treatment outcomes are often difficult to evaluate. The antibiotic regimens that are commonly used in clinical practice have changed rapidly. They show much regional variation with little critical comparison of treatment results. The clinical diagnosis and the literature on the treatment of the various stages of Lyme disease are reviewed. The reported data are supplemented with recommendations based on 15 years of clinical experience with this illness.     

Induction of monocyte chemotaxis in devascularized rabbit bone

Summary Temporary impairment of blood supply has been suggested to cause bone remodeling. The degradation of cells and matrix and the attraction of resorbing cells were examined in this study. Bone specimens of rabbits were stored in vitro for 2–20 days. At the end of this aging process the probes were tested for their chemotactic activity toward autologous leukocytes in a diffusion chamber. Both supernatant from the aged bone specimens and ground bone particles exhibited significant chemotactic activity that was specifically attracting monocytes. It is suggested that soluble bone matrix proteins or degeneration products liberated during ischemic damage to cortical bone initiate the resorptive process.This work was supported by the Swiss National Science Foundation, grant no. 3.857.0.83, and by the Studienstiftung des deutschen Volkes     

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.