Cryptogenic cirrhosis: clinical characterization and risk factors for underlying disease.

We characterized 70 consecutive patients with cryptogenic cirrhosis to assess major risks for liver disease. Each patient was reevaluated for past alcohol exposure, scored by the International Autoimmune Hepatitis (IAH) score and assessed for viral hepatitis risks and risks for nonalcoholic steatohepatitis (NASH). The results were compared with 50 consecutive NASH patients, 39 nonalcoholic patients age 50 and over with cirrhosis from hepatitis C, and 33 consecutive patients with cirrhosis caused by primary biliary cirrhosis (PBC). Among the cryptogenic group, 49 (70%) were female, and the mean age was 63 +/- 11 years. Although ascites and variceal bleeding were common, almost one half lacked major signs of complicated portal hypertension. A history of Type 2 diabetes mellitus and/or obesity was present in 51 (73%). Nineteen (27%) patients had a history of blood transfusions antedating the diagnosis of cirrhosis. No clinical or histological features distinguished this group from the other patients, and 14 (74%) of these had a history of obesity and/or diabetes. Nineteen of the remaining nontransfused patients had indeterminant IAH scores but were histologically and biochemically indistinguishable from the others. Twelve of these (63%) also had a history of obesity and/or diabetes. Both diabetes and obesity were significantly more common in the cryptogenic cirrhotic patients compared with the cirrhotic patients with PBC or hepatitis C. In contrast, the prevalence of obesity and diabetes was similar to the NASH patients who were, on average, a decade younger. Although there is some diversity that indicates more than one cause, our findings suggest that NASH plays an under-recognized role in many patients with cryptogenic cirrhosis, most of whom are older, type 2 diabetic and obese females.

Subumbilical midline vascularity of the abdominal wall in portal hypertension observed at laparoscopy.

BACKGROUND: Large volume paracentesis is a common treatment of ascites. Injury to abdominal wall collateral veins during this procedure can lead to hemoperitoneum. Because of this concern, the midline below the umbilicus is often recommended as a site for paracentesis because of its presumed avascularity. METHODS: We examined the subumbilical peritoneal surface in 20 consecutive patients with liver disease undergoing diagnostic laparoscopy. This area was visualized by table tilting and confirmed by external finger compression. Nineteen patients had cirrhosis of various etiologies, and one had advanced fibrosis with evidence of portal hypertension. RESULTS: In these 20 patients, only 7 had avascular midlines below the umbilicus. Seven had small but definite veins running along the path of the urachus (median umbilical fold), and 6 had more prominent veins in this region. The internal landmarks in this region (median and medial folds) were frequently asymmetric with regard to the external appearance of the midline. CONCLUSION: The subumbilical midline in patients with portal hypertension is commonly vascular. When using this site for paracentesis, care should be exercised to identify venous structures with the narrow-gauge needle used to inject local anesthetic agent before placement of larger paracentesis needles.

Intrahepatic biliary endoscopy in sclerosing cholangitis.

Sclerosing cholangitis is usually diagnosed by clinical findings coupled with radiographic imaging of the bile ducts by ERCP. Direct imaging of both the intra- and extrahepatic biliary tree provides an opportunity to further study this disorder and its potential complications such as biliary malignancy. However, endoscopic visualization of the intrahepatic bile ducts in sclerosing cholangitis is potentially limited by the size of available cholangioscopes and the presence of strictures. Below, we report our initial results using a 0.8-mm fiberoptic endoscope placed through a partially steerable 1.8-mm guide catheter. The system allows visualization of the intrahepatic biliary tree beyond areas of stricture in the more distal ducts.

The effects of mercuric chloride on calmodulin-mediated Ca2+ transport in rat brain.

We have shown previously that mercuric chloride (HgCl2) inhibits in vitro vasopressin release from the isolated rat neurohypophysis with maximum inhibition occurring with 0.5 mM HgCl2. Associated with the inhibition of hormone release is an increase in 45Ca+2 uptake, an increase in cytosolic 45Ca+2, and a reduction of 45Ca+2 accumulation by mitochondria in the intact gland. In the present series of studies, the effect of HgCl2 on calmodulin (CM) function in neural tissue preparations is reported. Mercuric chloride (0.5 mM) reduced 45Ca+2 binding to CM purified from bovine neurohypophyses by 20% and inhibited endogenous CM-stimulated Ca,Mg-ATPase activity from rat brain mitochondria in a dose-dependent fashion. Ca,Mg-ATPase activity was inhibited by 50 and 80% with 0.5 and 5.0 mM HgCl2, respectively. CM-stimulation of Ca,Mg-ATPase activity was inhibited by calmidazolium (CMZ) with maximal inhibition seen with 0.1 mM CMZ. Reversibility of the HgCl2 interaction with CM was demonstrated using CM-stimulated phosphodiesterase (PDEase) activity from rat brain. HgCl2 inhibited both basal and CM-stimulated PDEase activity in a dose-dependent manner with maximum inhibition occurring with 1.0 mM HgCl2. Preexposure of CM to an inhibitory concentration (1.0 mM) of HgCl2 resulted in no loss of stimulatory PDEase enzyme activity. From these results, we conclude that HgCl2 reversibly interferes with 45Ca+2 binding to CM and also inhibits CM-regulated Ca+2 pumping enzyme systems in the neurohypophysis. The inhibition of vasopressin release from the intact gland in the presence of HgCl2 thus, may be associated with a disruption of calcium in the neurohypophysis.