Giant cell hepatitis: an unusual cause of fulminant liver failure

Giant cell hepatitis is a very rare disease of unknown origin. It has been hypothesized that drugs, viral infections, or autoimmune reactions may play a pathogenetic role. Here, we describe a 33 year old patient with bacterial bronchitis who was treated with doxycycline (100 mg/d) for one week. Furthermore the patient complained of malaise and a distinct jaundice. Liver parameters increased dramatically (AST 4670 U/l, ALT 5350 U/l, bilirubin 226 μmol/l) and liver function was impaired (INR = 1,45). The ultrasound scan showed a hepatomegaly with no signs of cirrhosis, normal spleen size and normal bile ducts; liver perfusion was normal. No evidence of Wilson's disease, hemochromatosis, autoimmune hepatitis, primary sclerosing cholangitis, primary biliary cirrhosis, hepatitis A, B, C and E, HIV, CMV, VZV, adenoviral infections, or paracetamol intoxication was found. Subsequently, the patient developed acute liver failure (AST 2134 U/l, ALT 2820 U/l, bilirubin 380 μmol/l, INR 3.0) and a beginning renal failure. Therefore, he was transferred to our transplant center. Due to increasing confusion and somnolence due to cerebral edema mechanical ventilation was needed. Because of an acute renal failure and severe hepatic encephalopathia MARS-hemodialysis was performed. Three weeks after the appearance of the jaundice he underwent liver transplantation (MELD 40). Surprisingly, in the explanted liver the diagnosis of giant cell hepatitis was made. Today--2 years after successful liver transplantation--the patient is in very good condition with normal liver function. In conclusion, giant cell hepatitis is a rare cause of acute liver failure that is often recognized only histologically.     

Liver transplantation in a subject with familial hypercholesterolemia carrying the homozygous p.W577R LDL-receptor gene mutation

Mutations within the low density lipoprotein (LDL)-receptor gene result in familial hypercholesterolemia, an autosomal dominant inherited disease. Clinical homozygous affected subjects die of premature coronary artery disease as early as in early childhood. We identified a girl at the age of five yr with clinical homozygous familial hypercholesterolemia presenting with achilles tendon xanthomas and arcus lipoides. Her total cholesterol reached up to 1050 mg/dL. Molecular characterization of the LDL-receptor gene revealed a homozygous p.W577R mutation. Despite intensive treatment interventions with the combination of diet, statins, colestipol, and LDL-apheresis, the patient developed symptomatic coronary artery disease at the age of 16 yr. Subsequently, orthotopic liver transplantation was performed to cure the defective LDL-receptor gene. Clinical follow-up for almost nine yr post-transplantation revealed excellent liver function, normal liver enzymes, normal LDL-cholesterol, and regression of both tendon xanthomas and symptomatic coronary artery disease. In conclusion, liver transplantation can effectively reduce LDL-cholesterol in a familial hypercholesterolemia recipient with subsequent regression of xanthomas and atherosclerosis. Timing is extremely important in these exceptional cases to exclude the demand for heart transplantation due to severe coronary artery disease. In addition, the identification of the LDL-receptor as etiology of clinical homozygous hypercholesterolemia is a prerequisite once liver transplantation is considered as therapeutic option.     

The internet as a tool for the renal community

The Internet has impacted health care. With the introduction of the personal health record (PHR), patients have an opportunity to track their physician visits, medications, and laboratory values online in a pleasant and informative learning environment. The PHR is a secure, online, Internet-accessible method of storing and easily retrieving health information about one's medical history, physician visits, laboratory values, and medications. The American Association of Kidney Patients (AAKP) has taken the leadership role in developing a PHR for patients of the kidney community. There are several barriers that patients experience when using the Web for health resources. These include inaccurate or self-serving information and marketing statements that can be misleading and dangerous. Poorly written or inappropriate information for patients can be problematic, as can an abundance of extraneous information. For the most part, the public often has no way to judge what is and is not credible based on the context of the article alone. This article gives the reader a review of several Web resources that are available for patients and also for renal professionals. They are largely from large nonprofit organizations like the AAKP, National Kidney Foundation, Medical Education Institute, American Society of Nephrology, or The Nephron Information Center (nephron.com). This article also reviews sites from The National Kidney Disease Education Program, Hypertension-Dialysis and Clinical Nephrology, National Institute of Diabetes and Digestive and Kidney Diseases, and DaVita.     

p53 Codon 72 polymorphism, loss of heterozygosity and high-risk human papillomavirus infection in a low-incidence German esophageal squamous cell carcinoma patient cohort

Epidemiological studies in endemic geographic regions for esophageal squamous cell carcinoma (ESCC) suggested a number of risk factors, including modifications of the p53 tumor suppressor by codon Arg72Pro polymorphism, loss of heterozygosity (LOH) or human papillomavirus type 16 or 18 (HPV 16/18) infection. The p53 Arg72 variant has been suggested to be a high-risk factor in HPV-associated tumors. The present study analysed these associations in a low incidence geographic region in Germany. Fifty-three paraffin-embedded tumors and 53 surrounding normal squamous epithelium were investigated. For detection of p53 codon Arg72Pro polymorphism, direct sequencing for exon 4 was conducted. LOH analysis was performed using three microsatellite markers at the p53 gene locus, and all cases were screened for high-risk HPV infection (HPV 16 and 18) with primer specific PCR and confirmed by sequencing. The p53 codon 72 genotype distribution was identical to published studies of normal Caucasian population, suggesting no general influence of this polymorphism on esophageal cancer risk in Germany. One case showed a p53 mutation in exon 4. p53 LOH was found in 13/44 (30%) informative cases without any correlation to histopathological characteristics. Of 53 (17%) samples, 9 showed HPV 16 or 18 infection. We found no association between p53 codon 72 genotypes and increasing HPV infection rates. Interestingly, 8/9 HPV-positive cases showed at least one p53 Arg72 allele. These results indicate an important role of p53 in ESCC also in low-incidence regions. In combination with the p53 Arg72 variant HPV infection could contribute to the risk of ESCC development in these cases, as has been demonstrated for high-risk regions.     

SKI-606 (bosutinib), a novel Src kinase inhibitor, suppresses migration and invasion of human breast cancer cells

Src family kinase activity is elevated in many human tumors, including breast cancer, and is often associated with aggressive disease. We examined the effects of SKI-606 (bosutinib), a selective Src family kinase inhibitor, on human cancer cells derived from breast cancer patients to assess its potential for breast cancer treatment. Our results show that SKI-606 caused a decrease in cell motility and invasion of breast cancer cell lines with an IC50 of approximately 250 nmol/L, which was also the IC50 for inhibition of cellular Src kinase activity in intact tumor cells. These changes were accompanied by an increase in cell-to-cell adhesion and membrane localization of beta-catenin. By contrast, cell proliferation and survival were unaffected by SKI-606 at concentrations sufficient to block cell migration and invasion. Analysis of downstream effectors of Src revealed that SKI-606 inhibits the phosphorylation of focal adhesion kinase (FAK), proline-rich tyrosine kinase 2 (Pyk2), and Crk-associated substrate (p130Cas), with an IC50 similar to inhibition of cellular Src kinase. Our findings indicate that SKI-606 inhibits signaling pathways involved in controlling tumor cell motility and invasion, suggesting that SKI-606 is a promising therapeutic for breast cancer.     

Anaesthesia for emergency caesarean section, 2000-2004, at the Royal Women's Hospital, Melbourne

The provision of anaesthesia for emergency caesarean section is a major part of the workload of obstetric anaesthetists and the urgency often dictates the mode of anaesthesia that can be provided. We have audited the provision of anaesthesia for 'immediate' caesarean sections over a four-year period following the introduction of a 'Code Green' system to coordinate a rapid response to an obstetric decision to proceed with an 'immediate' caesarean section. The records of all patients for whom a Code Green was called between July 2000 and June 2004 were studied. The reasons for the call, interval timings (for example decision-to-delivery interval) and type of anaesthesia used were collected. There were 444 Code Green procedures, of which 47 were excluded due to incomplete data. The most common indication was fetal distress' and the three most common types of anaesthesia used were general (n = 206), Epidural top-up (n = 106) and spinal (n = 65). Mean decision-to-delivery intervals (+/- SD) for all caesarean sections were 17 (+/- 6) minutes with general anaesthesia, 19 (+/- 9) minutes with epidural and 26 (+/- 9) minutes with spinal anaesthesia. Forty-five percent of calls were made between the hours of 0700 and 1700 h. General anaesthesia was most used between the hours of 0700 and 1700 h. A swift response to the call for an immediate caesarean section can be achieved when suitable facilities and procedures are in place. Administering an epidural bolus into an already established epidural catheter that is working effectively can allow a decision-to-delivery interval almost as short as general anaesthesia.     

Complex regional pain syndrome type-1: a rare complication of arteriovenous graft placement.

Complex regional pain syndrome (CRPS) type-1 (previously termed reflex sympathetic dystrophy syndrome) may be manifested as sympathetically mediated pain and swelling in an extremity. Among the numerous causes of reflex sympathetic dystrophy, the most common is trauma. We describe a 71-year-old diabetic man with endstage renal disease who presented with CRPS type-1 of the left hand one month after construction of a PTFE (polytetrafluroethylene) arteriovenous graft. The symptoms of CRPS improved greatly with stellate ganglion blocks and physical therapy.