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.     

Verletzungen der Handwurzel

A fall onto the hand can be followed by ligament ruptures, bone fractures or dislocated fractures of the carpus. The diagnosis is based on history, clinical evaluation, and X-ray examination in two perpendicular planes, followed if necessary by CT scan or MRI scan. Lesions of the scapholunate ligaments cannot be definitely excluded except by arthroscopy. As well as fractures of the carpometacarpal joints, fractures involving the ring structure of the carpus or ligament ruptures between carpal bones are frequently observed, and these lead to significantly impaired biomechanics. The prognosis is poor. The discontinuity of the ring must be repaired by means of osteosynthesis and/or suturing ligaments, with the carpal bones held in place by temporary arthrodesis using K-wires. Dislocation in this region requires rapid realignment, as untreated perilunate dislocation or dislocation of the lunate bone will lead to serious secondary damage, which can only be treated by salvage operations involving loss of function. Inappropriate treatment of an injury to the heel of the hand can lead to carpal collapse.     

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.     

Anterior Cruciate Ligament Reconstruction: State of the Art

Abstract The rupture of the Anterior cruciate ligament (ACL) belongs to the most common ligament injuries of the human knee joint. ACL rupture results in an increased anterior translation and internal rotation of the tibia. Untreated knee instability causes a disintegration of the roll and sliding movement and a high incidence of secondary meniscus and chondral damages with consecutive or advanced arthritic changes. For deciding on a conservative or operative therapy, it is necessary to develop a high-risk profile. Elderly, inactive patients without instability symptoms can be treated conservatively; younger, active people and complex ligament injuries should receive an ACL replacement. The goal is to eliminate instability by maintaining the physiological kinematics of the knee. Anterior cruciate ligament may be reconstructed arthroscopically assisted by autologous tendons. Predominantly, hamstring- and bone-patellar-tendon grafts are used. No significant differences in knee laxity, clinically and functionally, were observed between both grafts. Various reconstruction techniques, single- or double-bundle techniques, were described. Successful replacement depends on a correct tunnel placement and reconstruction of the physiological band tension, a sufficient mechanical stability of fixation, an impingement-free range of motion and an adequate rehabilitation. A high degree of patient satisfaction in clinical and functional outcome could be evaluated.     

Testing of drug release from film pellets with special consideration of the thickness of the polymer coating

The influence of the thickness of polymer films on drug release was studied by means of an apparatus, developed especially for the examination of film-coated pellets. To show the direct dependence of the thickness of the polymer layer on the process of liberation a sequence of ten coating steps was chosen. On the contrary the release of active ingredients of varying dissolution behaviour was synchronous and didn't depend on the pH-value of the medium. The results show, that by using the proper coating material the thickness of the layer can be used to control the drug liberation process. The comparison of the release from different coating steps in the apparatus described makes it possible to produce mixtures of pellets with both a quick onset and a long duration of action by using only one type of coating material.     

Toxicological investigations in the semiconductor industry: I. Studies on the acute oral toxicity of a complex mixture of waste products from the aluminium plasma etching process.

In dry etching processes--one of the sources of potential exposure to toxic wastes in the semiconductor industry--complex mixtures of inorganic and organic compounds arise from reactions between feed stock gases (BCl3/Cl2), top layers (aluminium photoresist), and the carrier gas (N2). Two different fractions of the complex mixture--one an ethanolic solution (ES) and the other an insoluble liquid residue (LR)--were examined for acute oral toxicity in rats. Analytical data showed that the ethanol soluble fraction contained mainly inorganic compounds, whereas the residue contained various halogenated hydrocarbons. Neither death nor behavioral changes occurred after oral administration and observation up to 23 days. ES caused a lower mean arterial blood pressure in both sexes, increased P-R-intervals in male rats, and caused some mild biochemical and hematological alterations and changes in relative organ weights compared to the control groups. Exposure to LR influenced food and water intake, and caused a significant decrease in body weights, signs of polyurie, as well as changes in various relative organ weights and biochemical and hematological parameters. The blood pressure of the male animals fell and the heart rates of both sexes decreased.     

Orthotopic liver transplantation at Groote Schuur Hospital.

We present data on 10 patients (5 men and 5 women, aged 21-56 yrs) with end-stage liver disease or tumour who underwent orthotopic liver transplantation at Groote Schuur Hospital between October 1988 and June 1991. Standard surgical techniques were used for procuring the donor liver, the recipient hepatectomy and the implantation of the liver. The venovenous bypass method was used in all but 2 patients. Postoperative immunosuppression was usually achieved with cyclosporin, azathioprine and low-dose steroids. Six patients were treated with prophylactic OKT3. Rejection episodes were treated with bolus doses of intravenous steroids. The indications for liver transplantation included chronic active hepatitis progressing to cirrhosis (5), biliary cirrhosis in association with inflammatory bowel disease (1), sclerosing cholangitis (2), alpha 1-antitrypsin deficiency (1), and tumour (1). All patients with chronic liver disease had experienced at least one complication, examples of which included encephalopathy, bacterial peritonitis, ascites, variceal bleeding and septicaemia. Serious postoperative complications included acute rejection of the transplanted liver, renal and liver failure that responded to intensive care support and medical management. One patient died on the 11th postoperative day with complications of bleeding oesophageal ulcer, shock and fungaemia. The remaining patients are alive and well 1-31 months after transplantation.     

Liver transplantation for erythropoietic protoporphyria liver disease.

In erythropoietic protoporphyria (EPP), there is excessive production of protoporphyrin, primarily in the bone marrow, resulting in increased biliary excretion of this heme precursor. Some patients will develop progressive liver disease that may ultimately require liver transplantation. However, excessive production of protoporphyrin by the bone marrow continues after transplantation, which may cause recurrent disease in the allograft. This study was performed to define post-transplant survival, the risk of recurrent disease, and specific management issues in patients transplanted for EPP liver disease. The patients studied consisted of twelve males and eight females, with an average age of 31 (range, 13-56) years at the time of transplantation. The estimated maximum MELD score prior to transplant was 21 (range, 15-29). Unique complications in the perioperative period were light induced tissue damage in four patients and neuropathy in six, requiring prolonged mechanical ventilation in four. Patient and graft survival rates were 85% at 1 year, 69% at 5 years, and 47% at 10 years. Recurrent EPP liver disease occurred in 11 of 17 patients (65%) who survived more than 2 months. Three patients were retransplanted at 1.8, 12.6, and 14.5 years after the initial transplant for recurrent EPP liver disease. In conclusion, the 5-year patient survival rate in patients transplanted for EPP liver disease is good, but the recurrence of EPP liver disease appears to diminish long term graft and patient survival.