Serum lipids during the first year following acute spinal cord injury.

Patients with chronic spinal cord injury (SCI) have low levels of high-density lipoprotein (HDL) cholesterol. The cause of this abnormality and its relation to SCI are unknown. We studied 100 consecutively admitted males with acute SCI prospectively for 1 year to determine changes in serum lipids following acute SCI and the relation of these changes to the level of injury and physical activity. Low-density lipoprotein (LDL), HDL, and total cholesterol and triglycerides were all decreased following acute SCI and gradually increased toward normal by 1 year. Serum HDL, LDL, and total cholesterol levels correlated with the level of SCI: levels were lower in quadriplegic compared with paraplegic patients. Serum HDL showed the greatest change following SCI, increasing by 26% in quadriplegic and 18% in paraplegic patients. These changes in serum lipid levels could not be explained by changes in alcohol consumption or body weight. We estimated that only 44% of the increase in HDL following SCI was associated with an increase in physical activity. We postulate that interruption of the autonomic nervous system influences lipid metabolism and serum lipid levels.

Failure of piezoelectric lithotripsy of a gallstone impacted in the gallbladder neck.

Failure of extracorporeal shockwave lithotripsy is most frequently related to total stone mass, the size of individual stones, or unrecognized stone calcification which interferes with the dissolution effects of orally administered bile salts. We report a case of piezoelectric extracorporeal shockwave lithotripsy failure in a young woman with a 2-cm stone impacted in the neck of the gallbladder. Despite adequate positioning of the shockwave focal point on two separate occasions, no fragmentation was achieved. The stone was subsequently retrieved after the woman underwent laparoscopic cholecystectomy. When treated ex vivo, the stone rapidly fragmented. We hypothesize that the impacted stone, lacking a uniform liquid interface, failed to fragment because of the inability of cavitational forces to achieve a surface effect.

Spinal cord injury is a risk factor for gallstone disease.

The purpose of this study was to determine the prevalence of gallstone disease among patients with a spinal cord injury. We identified all patients with a spinal cord injury of greater than 2 weeks' duration who died and underwent an autopsy between 1975 and 1985. These 38 patients with spinal cord injury were age-, sex-, and race-matched with 38 patients without spinal cord injury who underwent an autopsy during the same period. Gallstone disease was significantly more prevalent in patients with spinal cord injury (11 of 38 or 29%) compared to the control population (4 of 38 or 11%) (p less than 0.05; odds ratio of 3.46 with 95% confidence interval of 1.08-11.24). A significant difference in age or level or duration of spinal cord injury was not found between patients with spinal cord injury who had gallstone disease and those who did not. Possible explanations for this threefold increase in risk of gallstone disease among patients with spinal cord injury include abnormal gallbladder motility resulting in stasis, decreased intestinal transit leading to an abnormal enterohepatic circulation, and metabolic changes leading to abnormal biliary lipid secretion.

Ampicillin inhibits biliary cholesterol secretion.

There are compounds, other than bile salts, which influence biliary lipid composition. For example, the organic anions, bilirubin, and BSP, are secreted into bile and depress biliary phospholipid and cholesterol secretion. Ampicillin is also secreted into bile, but its effects on biliary lipid secretion are unknown. Therefore we measured biliary lipid secretion before, during, and after an ampicillin infusion. We infused bile salt pool depleted rats with a constant infusion of taurocholate. After biliary lipid secretion reached a steady state, the ampicillin solution was infused in a stepwise fashion. Within minutes after starting the ampicillin, bile flow and biliary ampicillin secretion increased. Simultaneously, biliary phospholipid and cholesterol, but not bile salt, secretion decreased significantly. The calculated lithogenic index of bile decreased significantly as well. Despite doubling the ampicillin infusion, neither biliary ampicillin, phospholipid, nor cholesterol secretion changed. After discontinuation of the ampicillin, bile flow and biliary ampicillin secretion decreased, while phospholipid and cholesterol secretion returned to normal. Ampicillin dramatically influences biliary lipid composition directly. It inhibits the biliary secretion of phospholipid and cholesterol, but not bile salt, and consequently reduces the molar percentage of cholesterol in bile.

Inhibition of biliary phospholipid and cholesterol secretion by bilirubin in the Sprague-Dawley and Gunn rat.

Bilirubin is one of several organic anions that selectively inhibit the biliary secretion of phospholipid and cholesterol without affecting bile salt secretion. To determine the site of this inhibition and gain insight into its mechanism, normal, Sprague-Dawley and homozygous Gunn rats were infused with unconjugated bilirubin and a water-soluble model conjugate, bilirubin ditaurate. Either unconjugated bilirubin or bilirubin ditaurate infused into Sprague-Dawley rats caused an increase in biliary bilirubin secretion from 2.1 +/- 0.3 to 315 +/- 15 nmol/min, whereas phospholipid and cholesterol secretion fell significantly, in parallel, to 25% of control. Bilirubin ditaurate infused into homozygous Gunn rats caused changes in biliary lipid and bilirubin secretion similar to those seen in Sprague-Dawley rats. Biliary bilirubin secretion rose from 0.9 +/- 0.6 to 303 +/- 9 nmol/min, whereas biliary phospholipid and cholesterol secretion fell to 28% of controls. In contrast, unconjugated bilirubin infused into Gunn rats caused only a slight increase in biliary bilirubin secretion, from 0.9 +/- 0.3 to 6.0 +/- 2.1 nmol/min, whereas biliary lipid secretion remained within 90% of control. These results indicate that the inhibition of biliary phospholipid and cholesterol secretion by bilirubin occurs after microsomal conjugation. It is possible that the more hydrophilic conjugates of bilirubin aggregate with intracellular phospholipid and cholesterol destined for bile. Consequently, micelle-forming bile salts could be prevented from recognizing or aggregating with these lipids and fail to promote their secretion into bile.

Effect of organic anions on biliary lipids in the rat.

Bile salts enhance the biliary secretion of phospholipid and cholesterol. Other amphipilic molecules, organic anions, are secreted into bile as well. We studied the effects of bilirubin and iodipamide, two chemically dissimilar organic anions, on biliary lipid secretion in the rat. We infused bile salt pool-depleted rats with a stepwise infusion of taurocholate and a constant infusion of organic anion. Both organic anions markedly inhibited the biliary secretion of phospholipid and cholesterol without affecting bile salt secretion. This inhibition, at least with iodipamide, was dose-dependent and fully reversible. Using tritiated water as a precursor, we measured hepatic and biliary cholesterol synthesis in the presence or absence of an iodipamide infusion to see if decreased lipid synthesis could explain decreased secretion. Despite the marked reduction in biliary cholesterol secretion, the specific activity of biliary cholesterol was unchanged during an iodipamide infusion. We suggest that organic anions interfere with the assembly of the biliary mixed micelle resulting in micelles that are deficient in phospholipid and cholesterol.

Neuropsychological dysfunction in acute viral hepatitis.

Neuropsychological dysfunction may precede, occur simultaneously with, or follow the icteric phase of viral hepatitis. Encephalitic and meningitic involvement appears to precede the onset of clinical hepatitis while the tremor syndrome usually follows the onset of illness. The Guillain-Barré syndrome, peripheral nerve disorders, and behavioral abnormalities may occur at any stage of the disease. Neuropsychological alterations noted during the prodrome of viral hepatitis usually clear without sequelae but abnormalities which follow the onset of jaundice may persist during the convalescent phase for prolonged periods. Neither occurrence, type, nor severity of neuropsychological dysfunction appear to be related to specific hepatitis viruses since both type B and non-B infections have been implicated. Furthermore, neuropsychological dysfunction does not appear to be related to the severity of the hepatitis as assessed by clinical or histological features. Although direct viral invasion of nervous tissue and immune complex-mediated damage have been postulated, the mechanism(s) of neuropsychological abnormalities remains to be determined.