Hematopoietic bone marrow hyperplasia: correlation of spinal MR findings, hematologic parameters, and bone mineral density in endurance athletes

To clarify the effects of obstructive jaundice on the liver, sequential changes of hepatic energy charge, the concentrations of adenine nucleotides and malondialdehyde, DNA synthesis rate, and histology of the liver were examined on the day before and Days 1, 2, 4, 7, and 14 after biliary obstruction in rats and compared with those of sham-operated controls. Foci of necrotic hepatocytes were present on Days 1 and 2 and mitoses of the hepatocytes were frequently observed with a peak on Day 2 in the jaundiced liver. Marked proliferation of bile ductules were subsequently observed on Days 7 and 14, resembling biliary cirrhosis. The DNA synthesis rate was significantly activated after bile duct obstruction with its peak on Day 2, more than nine times higher than the control value and returned to the control level on Day 14. Hepatic ATP concentration and energy charge gradually declined with prolonged jaundice and significantly lower levels persisted after Day 7 compared with the controls. The malondialdehyde level in the jaundiced liver gradually increased and became significantly higher on Day 14. We conclude that obstructive jaundice decreases hepatic energy charge and increases the lipoperoxide level. In the initial stage of obstructive jaundice, the hepatocytes proliferate associated with activated DNA synthesis probably to compensate hepatic damage; however, prolonged obstructive jaundice induces functional hepatic injury possibly necessitating biliary drainage.     

Treatment of extrahepatic occlusive jaundice with activated charcoal hemoperfusion in dogs

To find the feasibility of treatment for congenital bile duct atresia, we studied the usefullness of extracorporeal hemoperfusion over activated charcoal in canine obstructive jaundice. One, three and five weeks after ligation and disection of common bile duct in 5 dogs we performed the hemoperfusion over activated charcoal extracorporeally (group 3). In this animals we examined hematological and blood coagulation studies, serum electrolyte levels, kidney function tests and liver chemistries. As control in 5 animals we carried out after sham operation the perfusion without common bile duct ligation (group 2) and in 5 animals only common bile duct ligation without perfusion (group 1). In the liver chemistries we found 2 weeks after 2nd and 3rd perfusion (5 and 7 weeks after bile duct ligation) lower levels of serum bilirubin, GOT, GPT and SDH in treated group than in non-treated jaundiced animals. It suggest the effectiveness of hemoperfusion with activated charcoal in the treatment of occlusive jaundice. There were no alteration in the hematological studies, serum electrolyte levels and kidney function tests. PT and PTT was prolonged in the jaundiced animals there were no significant differences with and without hemoperfusion.     

Role of endotoxin and nitric oxide in the pathogenesis of renal failure in obstructive jaundice

BACKGROUND: There is an increased incidence of postoperative renal failure in patients with obstructive jaundice. The purpose of this study was to investigate the role of endotoxaemia and nitric oxide in this association. METHODS: In bile duct-ligated, sham-operated and control rats, plasma total bilirubin levels, creatinine clearance and plasma endotoxin were determined. Endothelium-dependent vasodilatation to acetylcholine, and endothelium-independent vasodilatation to nitroglycerine and forskolin were evaluated in isolated perfused rat kidney. RESULTS: Twenty-one of 27 bile-duct ligated rats had endotoxaemia. Plasma bilirubin levels were higher and creatinine clearance was significantly reduced in the bile duct-ligated endotoxin-positive group compared with values in the other groups. Furthermore, in the isolated perfused rat kidney from rats with endotoxaemia, basal perfusion pressure and renal vascular relaxation to acetylcholine and nitroglycerine which is mediated by guanosine cyclic 3',5'-cyclic monophosphate (cGMP) were significantly reduced, but relaxation to forskolin mediated by adenosine cyclic 3',5'-cyclic monophosphate did not change. CONCLUSION: Endotoxaemia in obstructive jaundice may induce overproduction of nitric oxide that may lead to impairment of cGMP-associated vasodilatation and disrupt autoregulation of the renal vascular bed. This may contribute to renal failure in obstructive jaundice.     

Bile and bilirubin excretion in relation to hepatic energy status during hemorrhagic shock and hypoxemia in rabbits

OBJECTIVE: We investigated the relation between in vivo hepatocyte excretion of bile and bilirubin and hepatic energy status in rabbit models of hemorrhagic shock and hypoxemia. DESIGN: Randomized animal study. MATERIALS AND METHODS: After creation of a total biliary fistula, hemorrhagic shock with mean pressure of 50 mm Hg (10 rabbits) or hypoxemia with Pao2 at 35 mm Hg (8 rabbits) was induced for 60 minutes. We determined bile flow, excretion of bilirubin and total bile acids, the plasma level of bilirubin, and arterial ketone body ratio, which reflects hepatic mitochondrial function. MEASUREMENTS AND MAIN RESULTS: Both the hemorrhagic shock and the hypoxemic models showed decreases in bile flow and excretion of bilirubin and total bile acids as well as increase in the plasma level of bilirubin in association with decreases in the hepatic energy charge and the arterial ketone body ratio. CONCLUSIONS: Bile flow and the excretion of bilirubin were correlated with the hepatic energy status.     

Jaundice associated with polycystic liver disease. Relief by surgical decompression of the cysts

Jaundice is an unusual feature of polycystic liver disease. In a 46-year-old woman with polycystic liver disease and jaundice, the bilirubin level was 42.0 mg/100 ml. Because of the rapid rise in bilirubin level, relief of supposed obstruction of intrahepatic bile ducts was attempted by unroofing the hepatic cysts. Following operation the bilirubin level returned to normal, and the patient has remained well since.     

Obstructive jaundice due to multiple hepatic abscesses

A 63-year-old Japanese male with diabetes mellitus developed obstructive jaundice following the onset of multiple hepatic abscesses. Percutaneous transhepatic cholangiography showed intrahepatic bile duct irregularity and dilatations accompanied by a complete obstruction of the right branch of the intrahepatic bile duct. Three kinds of organisms were cultured from the blood and the drained bile. The cholangiographic changes returned to the normal after the liver abscesses subsided following biliary drainage and the administration of intravenous antibiotics.     

Hepatic adenine nucleotides and microsomal cholesterol 7 alpha-hydroxylase activity in the obstructed and freely draining lobes of the liver after selective bile duct obstruction

BACKGROUND: The effect of selective bile duct obstruction (SBDO) on hepatic reserve function of the bile duct obstructed (BDO) and nonobstructed freely draining (FD) lobes of the liver is obscure. METHODS: The bile duct branches draining from the left lateral and median lobes of the liver were ligated for 4 and 10 days in rats, and hepatic reserve functions in BDO and FD lobes were assessed by microsomal cholesterol 7 alpha-hydroxylase activities and by hepatic adenine nucleotides and energy charge levels. The values were compared with those in the sham-operated control liver. Cholesterol 7 alpha-hydroxylase activities were determined by gas-liquid chromatography--mass spectrometry, and hepatic adenosine triphosphate (ATP), adenosine diphosphate (ADP), and adenosine monophosphate (AMP) levels with high-pressure liquid chromatography. RESULTS: The histological examination of the BDO lobes showed proliferation and formation of new bile ductules and fibrous connective tissues linking portal areas. Microsomal cholesterol 7 alpha-hydroxylase activities, hepatic energy charge and each adenine nucleotide level did not differ between FD and BDO lobes, and the values were similar to those in the sham-operated liver. CONCLUSIONS: Selective bile duct obstruction shows no adverse effects on microsomal and mitochondrial functions in both the BDO and FD lobes of the liver.     

Hematological and blood biochemical effects of fasting and subsequent oral administration of endotoxin in prepubertal gifts

The main objective of the present study was to investigate the effects of short-term fasting in gilts on endocrinological and blood biochemical parameters and, further, the effects of subsequent oral endotoxin (ET) administration. Group 1 was fasted for 30 h and then received feed with ET added. Group 2 was fasted for 30 h but received standard feed at refeeding. In group 3, gilts were fed every 6 h for 30 h. The major effects of fasting were: gradually increased concentration of plasma prostaglandin F2 alpha metabolite, serum total bilirubin, serum free fatty acids, and decreased serum glucose. The values were normalized within 1-4 h of refeeding. Twelve hours after refeeding, the ET-refed gilts showed higher levels of serum total bile acids and polymorphonuclear leukocytes than those in group 2. It is possible that the observed changes during fasting reflect either an increased intestinal uptake of naturally present endotoxin or a reduced endotoxin detoxifying capacity of the liver. The increased bile acid concentration and polymorphonuclear leukocyte count following refeeding with ET-feed may indicate that orally administered ET is to some extent absorbed from the gut.     

Homeless patients in the psychiatric clinic. Results of a 12-month study of the living conditions of psychiatric patients in an urban public health clinic

BACKGROUND: Percutaneous transhepatic biliary drainage (PTBD) has been employed for decompression of the obstructed biliary tract to palliate jaundice and pruritus and for the management of cholangitis. We present our data to review the indications, therapeutic results and associated mortality and complications of this procedure. We have also studied the effect of size of drainage catheters on the improvement in liver functions and procedure related complications. METHODS: PTBD was attempted in 41 patients (18 men, age 56 +/- 12 years; 23 women, age 55 +/- 11 years) with obstructive jaundice (37 malignant, 4 benign). RESULTS: PTBD was successful in 39 (95%) patients. Mean serum bilirubin and alkaline phosphatase concentration declined significantly (p < 0.000001 for both) after 1 week, however thereafter decline was slow. Complete relief of pruritus and cholangitis was noted in most patients. Major complications such as cholangitis, bile leak into the peritoneum, malfunction of drainage catheter, intraperitoneal haemorrhage and renal failure, occurred in 11 (28%) patients, 2 (5%) of whom died. Large catheters (> 10 Fr) were superior to small size catheters (< 10 Fr) in relief of jaundice and had lower catheter related cholangitis. CONCLUSIONS: We conclude that PTBD is useful for palliation of malignant obstructive jaundice with intractable symptoms and cholangitis. Catheters larger than 10 Fr should be used.     

Insufficiency of the urea-synthesizing function of the liver and its correction in mechanical jaundice

From the moment of the rise of blood bilirubin level extrahepatic bile stasis is accompanied by hepatic insufficiency, the first preclinical manifestation of which is the increase of urea level in the liver tissue. Parallel with the hyperbilirubinaemia there is the increase of inhibition of urea-synthetizing liver function, resulting in the rise of ammonia level in the liver tissue and in the blood, which has both local and general toxic effect. The injection of retabolil 2 to 7 days preoperatively produces a favourable clinical effect, which permits to recommend this procedure to be introduced into the preoperative therapeutic complex in case of mechanical jaundice.     

Endothelin A-receptor blockade worsens endotoxin-induced hepatic microcirculatory changes and necrosis

BACKGROUND & AIMS: Endothelin 1 is considered to be an important regulator of sinusoidal blood flow and increases during endotoxemia. The purpose of this study was to investigate the role of endothelin 1 in hepatic microcirculation, oxygen transport, and liver injury during endotoxemia. METHODS: Male Sprague-Dawley rats were continuously infused with 2.5 mL/h of saline, 0.8 mg . kg-1 . h-1 of lipopolysaccharide (LPS), 3 mg . kg-1 . h-1 of BQ-485, an endothelin A-receptor antagonist, or LPS plus BQ-485 for 7 hours. RESULTS: BQ-485 infusion had no significant effect on hepatic microcirculation and liver injury. LPS increased the plasma levels of aspartate aminotransferase (AST) and total bilirubin and decreased the hepatic adenosine triphosphate (ATP) level and bile flow rate. LPS + BQ-485 infusion further increased the plasma levels of AST and total bilirubin and decreased the bile flow rate and the hepatic ATP level. Dual-spot microspectroscopy revealed mild decreases in sinusoidal erythrocyte velocity and oxygen transport in the LPS group and profound decreases in these parameters in the LPS + BQ-485 group. Histological examinations revealed massive necrotic changes in the pericentral regions of the LPS + BQ-485 group. CONCLUSIONS: These results suggest that blockade of endothelin A receptors disturbs hepatic microcirculation and oxygen transport and aggravates the necrotic injury induced by endotoxin.     

Metabolism of insulin and glucagon in liver and pancreas in dogs with obstructive jaundice

Insulin and glucagon metabolism in the pancreas with obstructive jaundice caused by complete ligation of the common bile duct and in the cholestatic liver caused by hepatic duct ligation was evaluated experimentally using dogs. The isolated perfused pancreas in obstructive jaundiced dogs, which showed a low insulin response in the peripheral blood after intravenous glucose administration, revealed depression of insulin production and no change of glucagon production in response to cholecystokinin octapeptide. The extraction of insulin in the cholestatic lobe of the liver was decreased compared with that in the noncholestatic lobe. The extraction of glucagon, on the other hand, in the cholestatic lobe and in the noncholestatic lobe showed no significant difference. So the imbalance of glucose metabolism in obstructive jaundice does not depend on the enhanced extraction of insulin in the liver, but on the depression of insulin production in the pancreas.     

Prolonged intrahepatic cholestasis in acute-onset, severe autoimmune hepatitis

A 72-year-old woman was admitted because of jaundice and hepatocellular dysfunction. She was diagnosed with autoimmune hepatitis from laboratory test results showing high titers of antinuclear antibodies and negativity for hepatitis viral markers. Steroid i.v. pulse therapy and oral administration of prednisolone were effective in improving the liver function test results, except for hyperbilirubinemia. Elevated serum bilirubin levels, of approximately 20 mg/dl persisted for more than 6 months, despite the administration of ursodeoxycholic acid. Insulin-glucagon therapy was given for normalization of transaminases and then withdrawn 3 weeks after admission, but it was resumed at 3 months, resulting in a dramatic decrease in serum bilirubin levels, which then normalized in 2.5 months. Liver biopsy 6 months after onset showed chronic active hepatitis with bile plugs. Insulin-glucagon therapy, because of its choleretic effect, may be worth continuing even after recovery of acute hepatic failure.     

K+ Channel density increases selectively in the endfoot of retinal glial cells during development of Rana catesbiana

BACKGROUND: We investigated the bile duct wall thickness measured on intraductal US in patients who had not undergone biliary drainage, with special attention to the influence of cancer at the distal bile duct, bile duct stones, obstructive jaundice, longitudinal cancer extension, and primary sclerosing cholangitis on wall thickness. METHODS: The study included 183 patients. Patients who had undergone previous biliary drainage were excluded. Intraductal US was performed by the transpapillary route with use of a thin-caliber ultrasonic probe (2.0 mm diameter, 20 MHz frequency). The bile duct wall thickness (width of the inside hypoechoic layer) was retrospectively measured on US images. RESULTS: Bile duct wall thicknesses of the common hepatic duct for the control group (n = 95), cancer at the distal bile duct group (n = 9), bile duct stone group (n = 56), and obstructive jaundice group (n = 17) were 0.6 +/- 0.3 mm (mean +/- SD), 0.8 +/- 0.5 mm, 0.8 +/- 0.6 mm, and 0.8 +/- 0. 5 mm, respectively. No significant differences (p > 0.05) were found between them. However, wall thickness for the cancer extension to the common hepatic duct group (n = 4, 2.0 +/- 0.4 mm) and sclerosing cholangitis group (n = 2, 2.5 +/- 0.4 mm) were significantly greater than in the other groups (p < 0.005). CONCLUSIONS: In patients who have not undergone previous biliary drainage, the bile duct wall thickness was not thicker in patients with obstructive jaundice. However, the duct wall was significantly thicker in patients with either longitudinal cancer extension or primary sclerosing cholangitis compared with that of other groups.     

Metabolism of 14C-labelled alphaxalone in man

The metabolism of 14C-labelled alphaxalone, dispensed as Althesin, was studied in normal patients, patients with obstructive jaundice and patients with chronic renal disease and anuria. The radioactive label was removed rapidly from the plasma following i.v. administration. The major portion of the label was excreted in the urine. In patients with normal renal function 14C-labelled alphaxalone is probably taken up by the liver, metabolized to a more polar compound and excreted in the urine; a small amount is excreted in the bile. In the patient with anuria, hepatic uptake appears to be relatively normal and the length of action of Althesin is not prolonged. It is assumed that in such patients the eventual route of excretion is via the bile and faeces.     

Hepatic mitochondrial changes in experimental obstructive jaundice complicated by biliary infection

The effects of biliary infection on the structural and functional changes in the liver in obstructive jaundice was studied using rats as experimental animals. Biliary infection with obstructive jaundice was induced in the animals by injecting Escherichia coli into the common bile duct through a nylon tube cannulated into the duct. This was followed by the clamping of the tube. For the controls, the tube was clamped in the absence of Escherichia coli. After 3, 7, 14 and 21 days, the animals were sacrificed, and some serum enzyme activities, histological changes in the liver, and the coupling efficiency of mitochondria isolated from the liver were investigated. The phosphorylating ability of hepatic mitochondria was more seriously affected when the obstruction was complicated by cholangitis. We suggest that, when associated with obstructive jaundice, biliary infection should be carefully treated prior to hepatectomy.     

Indicators of liver excretory function in patients undergoing biliary decompression for obstructive jaundice

BACKGROUND/AIMS: The recovery of liver function after biliary drainage in patients with obstructive jaundice may be different depending on the severity and duration of the obstruction. We conducted this study to determine whether there are any clinical factors that can be used to monitor the course of recovery. METHODOLOGY: Serum and bile from 12 patients were collected for biochemical testing on the day of drainage and every 3 days for 6 days. Liver function was evaluated by the indocyanine green retention test (ICG R15) before and 6 days after decompression. Patients with an ICG R15 reduction ratio of less than 50% were considered to have a poor recovery (group 1, n = 6), while a good recovery was indicated by a reduction ratio higher than 50% (group 2, n = 6). Sequential data were compared between the groups and correlated with the results of the ICG test. RESULTS: After drainage, the patients in group 1 had less bile acid excretion on day 3 (1.0 +/- 0.8 vs. 3.4 +/- 1.1 mmol/day, p < 0.05), a slower reduction ratio of serum bilirubin on day 3 (0.38 +/- 0.14 vs. 0.60 +/- 0.12, p < 0.05) and more biliary output on day 6 (1.11 +/- 0.25 vs. 0.60 +/- 0.25 L/day, p < 0.05). The ICG R15 reduction ratio was well correlated with the bilirubin reduction ratio, the bile volume and the amount of excreted bile acids checked on day 3 (gamma = 0.73, -0.71 and 0.74, respectively, p < 0.01). CONCLUSIONS: The presence of choleresis implies ductular cell hyperplasia, while decreased excretion of bile acids and a slow reduction of hyperbilirubinemia represents severe liver damage. Both conditions are sequelae of prolonged obstruction; therefore, they might indicate a long and poor recovery.     

Interobserver variation in the assessment of the sampling quality of cervical smears

The present study was carried out to investigate the biochemical and morphological changes in the liver after ligation of the hepatic artery (HA) in the presence and in the absence of extrahepatic cholestasis (EHC). The study was conducted on 100 rats divided into four groups of 25 animals each: group 1, sham operation; group 2, hepatic artery ligation (HAL); group 3, bile duct ligation (BDL); and group 4, HAL plus BDL. All animals were sacrificed 7 days after surgery when total bilirubin and fractions, alkaline phosphatase (AP), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured in serum and on the inner hepatocyte mitochondrial membrane (IHMM); the incidence of necrosis and the volume fractions of vessels, bile ducts and hepatocytes in the liver were also determined. HAL reduces the relative volumes of bile ducts, with no changes in levels of bilirubin and fractions, AP, ALT, AST and IHMM, but HAL associated with EHC reduces duct proliferation and the liver becomes more vulnerable to necrosis. In conclusion, the normal liver depends on HA flow and this dependence is more evident in the presence of EHC.     

Common foot deformities in infancy and childhood

An enzymatic-fluorimetric method using a highly purified 3alpha-hydroxysteroid dehydrogenase (Sterognost-3alpha, Nyco) was used to determine fasting serum bile acid concentrations on 49 occasions in 43 patients with various liver diseases. A two-hour postprandial bile acid determination was carried out on 29 occasions in 27 of the patients. Fasting bile acid concentration correlated significantly both in cholestatic hepatobiliary and in parenchymatous liver disease to serum bilirubin and aspartate aminotransferase (ASAT) but not to alanine aminotransferase (ALAT), alkaline phosphatase, or albumin. The two-hour postprandial bile acid concentration was above normal in all patients with biochemical and/or histological signs of hepatobiliary disease, also when fasting concentration was within normal limits. In parenchymatous liver disease correlations existed between the two-hour postprandial bile acid concentration and bilirubin, ASAT, and ALAT. The sensitivity of serum bile acid estimation was compared to other liver function tests. Both the fasting and the postprandial serum bile acid concentrations tended to be more sensitive tests of hepatobiliary disease than bilirubin, ASAT and ALAT.     

Midazolam-flumazenil topical anaesthesia for microlaryngoscopy with jet ventilation

BACKGROUND: Enhanced production of endothelin-1 (ET-1), vasoconstrictive 21 amino acids produced by endothelial cells during ischemia and after reperfusion of the liver, is known to cause sinusoidal constriction and microcirculatory disturbances, which lead to severe tissue damage. Using a 2-hour hepatic vascular exclusion model in dogs, we tested our hypothesis that neutralization of ET-1 by monoclonal anti-ET-1 and anti-ET-2 antibody (AwETN40) abates vascular dysfunction and ameliorates ischemia/reperfusion injury of the liver. STUDY DESIGN: After skeletonization, the liver was made totally ischemic by cross-clamping the portal vein, the hepatic artery, and the vena cava (above and below the liver). Veno-venous bypass was used to decompress splanchnic and inferior systemic congestion. AwETN40, 5 mg/kg, was administered intravenously 10 minutes before ischemia (treatment group, n = 5). Nontreated animals were used as controls (control group, n = 10). Animal survival, hepatic tissue blood flow, liver function tests, total bile acid, high-energy phosphate, ET-1 levels, and liver histopathology were studied. RESULTS: Treatment with AwETN40 improved 2-week animal survival from 30% to 100%. Hepatic tissue blood flow after reperfusion was significantly higher in the treatment group. The treatment significantly attenuated liver enzyme release, total bile acid, and changes in adenine nucleotides. Immunoreactive ET-1 levels in the hepatic venous blood of the control group showed a significant increase and remained high for up to 24 hours after reperfusion. Histopathologic alterations were significantly lessened in the treatment group. CONCLUSIONS: These results indicate that ET-1 is involved in ischemia/reperfusion injury of the liver, which can be ameliorated by the monoclonal anti-ET-1 and anti-ET-2 antibody AwETN40.