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.     

Epidemiology, the humanities, and public health.

Epidemiologists may benefit from the disciplines of history, philosophy of science, ethics, literature, and art. Within these disciplines lie answers to the questions of who we are, what is right, how to think, and when to act. Studying and participating in the humanities may also help epidemiologists focus their professional concerns on the humanity their methods serve. A parallel phenomenon in the clinical sciences--medical humanities--provides support for the approach (and some lessons).     

Androgen receptor YAC transgenic mice carrying CAG 45 alleles show trinucleotide repeat instability

X-linked spinal and bulbar muscular atrophy (SBMA) is caused by a CAG repeat expansion in the first exon of the androgen receptor (AR) gene. Disease-associated alleles (37-66 CAGs) change in length when transmitted from parents to offspring, with a significantly greater tendency to shift size when inherited paternally. As transgenic mice carrying human AR cDNAs with 45 and 66 CAG repeats do not display repeat instability, we attempted to model trinucleotide repeat instability by generating transgenic mice with yeast artificial chromosomes (YACs) carrying AR CAG repeat expansions in their genomic context. Studies of independent lines of AR YAC transgenic mice with CAG 45 alleles reveal intergenerational instability at an overall rate of approximately 10%. We also find that the 45 CAG repeat tracts are significantly more unstable with maternal transmission and as the transmitting mother ages. Of all the CAG/CTG repeat transgenic mice produced to date the AR YAC CAG 45 mice are unstable with the smallest trinucleotide repeat mutations, suggesting that the length threshold for repeat instability in the mouse may be lowered by including the appropriate flanking human DNA sequences. By sequence-tagged site content analysis and long range mapping we determined that one unstable transgenic line has integrated an approximately 70 kb segment of the AR locus due to fragmentation of the AR YAC. Identification of the cis - acting elements that permit CAG tract instability and the trans -acting factors that modulate repeat instability in the AR YAC CAG 45 mice may provide insights into the molecular basis of trinucleotide repeat instability in humans.      

Evaluation of calcium alginate-tipped aluminum swabs transported in Culturettes containing ampules of 2-sucrose phosphate medium for recovery of Chlamydia trachomatis

Two calcium alginate-tipped wire swab specimens were obtained from 94 men and 106 women attending a sexually transmitted disease clinic. One swab was extracted thoroughly in 2-sucrose phosphate (2SP) immediately after obtaining the specimen. The second swab was returned to the Culturette cylinder (Marion Scientific, Kansas City, MO), and the ampule containing 2SP was crushed to moisten the swab during transport to the laboratory. After receipt in the laboratory, the swab was removed from the Culturette and extracted into 2 mL of 2SP. Both specimens then were cultured for the presence of Chlamydia trachomatis in McCoy's cells. C. trachomatis was recovered from 22 of 94 men (23.4%); 16 isolates came from both the Culturette swabs and vials. Six isolates were recovered exclusively from vials. Of 106 women, 13 (12.3%) were positive for C. trachomatis. In five instances, both vials and swabs yielded C. trachomatis; the organism was recovered eight times from vials but not swabs. The 2SP transport system for the 200 specimens was superior to the Culturettes for the recovery of C. trachomatis (P less than 0.01). Based on our results, swab specimens taken for laboratory diagnosis of C. trachomatis should be extracted immediately after collection in a vial containing 2SP. In addition, experiments comparing swab fibers indicated that there was a trend indicating higher inclusion counts with rayon-tipped swabs, compared with those containing calcium alginate. Because of possible toxicity of substances in calcium alginate fibers for several organisms causing sexually transmitted disease, rayon-tipped swabs or swabs of other composition should be used.     

Effect of tactile stimulation pulse characteristics on sensation threshold and power consumption

The psychophysical responses of human subjects to vibratory tactile stimulation of the skin were investigated experimentally. The parameters, of the waveform important to the minimization of power consumed by the tactile array of electromechanical vibrators and the maximization of the skin sensitivity to the stimulus were explored to develop optimum stimulation. Parameters investigated included the amplitude, frequency, and duty cycle of the current waveform used to drive the vibrators as well as the number of pulses per stimulating burst and the recovery time between bursts. Graphical techniques were used to determine, the optimal combination of the parameters which gave a stimulus that excited the skin to above tactile threshold while maintaining at a relative minimum the power required for the stimulus. The optimal stimulation waveform contains a burst of 10 rectangular pulses of 4% duty cycle separated by a period of nonstimulation of 2 s. Such a waveform can elicit a sensitivity of 29.4 mA⁻¹ consuming only 55 μW of power.