Cefamandole kinetics in uremic patients undergoing hemodialysis.

A single intravenous 15 mg/kg dose of cefamandole was given to 6 patients in chronic renal failure before hemodialysis, and 3 were examined during an interdialysis period. Mean cefamandole clearance by hemodialysis was 24 +/- 12 ml/min; 35 +/- 15% of the dose was recovered in the dialysate. The cefamandole half-life (1 1/2) on dialysis was 4.0 +/- 0.29 hr; off dialysis it was 13.9 +/- 4.2 hr. High urine concentrations of cefamandole in these patients suggests usefulness in urinary tract infection.     

Clinical evaluation of serum levels of tryptophan in hepatobiliary disease

Fasting serum levels of total and free tryptophan, and free fatty acids and albumin, were measured and compared by blood biochemical analysis in patients with hepatobiliary disease and neuropsychiatric symptoms. The serum total tryptophan level tended to be elevated in patients with chronic active hepatitis, hepatic coma and obstructive jaundice, but not significantly. The serum free tryptophan level was significantly elevated in patients with chronic active hepatitis, liver cirrhosis, primary hepatocellular carcinoma and obstructive jaundice. The free tryptophan level was related to the decreased serum albumin level and elevated serum free fatty acid levels, which seems to indicate a connection with liver parenchymal function. The level, however, seemed not to correlate with neuropsychiatric symptoms.     

Glycylprolyl-p-nitroanilidase in hepatobiliary disease

The serum activity of glycylprolyl-p-nitroanilidase (GPN) has been compared with isocitrate dehydrogenase and with alanine and aspartate aminotransferases in patients with hepatobiliary diseases, myocardial infarction and chronic inflammatory bowel disease. Serum GPN was markedly increased in all hepatobiliary diseases, especially secondary carcinoma and chronic alcoholic hepatitis, but no abnormal values were seen in patients with chronic inflammatory bowel disease. Slightly elevated GPN activities were noticed in a few cases of myocardial infarction. It is suggested that serum GPN would be useful for monitoring hepatic function, especially in the clinical trials of new drug.     

Serum squalene levels in hepatobiliary diseases

Serum squalene levels did not change in patients with acute hepatitis, chronic active hepatitis and liver cirrhosis, but were significantly reduced in patients with intra- and extrahepatic cholestasis. The ratio of cholesterol to squalene remained normal in patients with acute hepatitis as well as chronic active hepatitis, while being slightly decreased in patients with liver cirrhosis. On the other hand, in patients with cholestasis the ratio was markedly raised. From these observations we confirmed abnormal sterol metabolism in hepatobiliary diseases, and clinical usefulness of the ratio of cholesterol to squalene to distinguish hepatocellular injury and cholestasis.     

A comparative study of intravenous cholangiography and99mTc-pyridoxylideneglutamate in patients with hepatobiliary disease

The purpose of this investigation was to compare the diagnostic value of intravenous cholangiography with^99mTc-pyridoxylideneglutamate, a new radioisotopic biliary imaging agent, in 15 patients with suspected hepatobiliary disease. Each subject had both examinations, and the studies were interpreted independently. The results suggest that intravenous cholangiography may provide more specific information about the ductal system but is of limited value in patients with elevated bilirubin. In these patients^99mTc-pyridoxylideneglutamate may show patency of the bile ducts and distinguish between partial and complete biliary tract obstruction. Depending upon the serum bilirubin level, both studies may provide useful and complementary information about the biliary tract.Picker Scholar, James Picker Foundation     

ED ultrasound in hepatobiliary disease

To evaluate the diagnostic accuracy of gallbladder ultrasound performed by emergency physicians (EPUS) in patients with right upper quadrant (RUQ) and epigastric (EPI) pain, adults>18 years of age with RUQ or EPI pain were prospectively evaluated by physical examination, laboratory data, and EPUS followed by a blinded radiology department ultrasound (RADUS). Diagnostic categories included: "normal gallbladder"; "uncomplicated symptomatic cholelithiasis" (uncomplicated SCL; stones present but symptoms and signs relieved and no abnormal blood-work); or "complicated symptomatic cholelithiasis" (CSCL; stones and positive symptoms and signs including abnormal blood-work). Final Emergency Department patient assessments based on the RADUS were compared to the EPUS. Over 2-years, 127 patients were enrolled. The sensitivity of the EPUS for detecting stones was 94% (positive predictive value 99%; specificity 96%; negative predictive value 73%). In conclusion, the EPUS is a highly sensitive and reliable indicator of the presence of gallstones.     

Plasma homocysteine levels in L-dopa-treated Parkinson's disease patients with cognitive dysfunctions.

Elevated plasma homocysteine (Hcy) concentrations are associated with Alzheimer's disease and vascular dementia. Several recent reports have indicated that L-dopa treatment is an acquired cause of hyperhomo-cysteinemia. Despite the fact that a large proportion of Parkinson's disease (PD) patients develop cognitive dysfunctions or dementia, particularly in the late stages of the illness and after long-term L-dopa treatment, the relationship between Hcy and dementia in PD has not been fully investigated. The aim of this study was to evaluate plasma Hcy levels in a group of L-dopa-treated PD patients with cognitive impairment and to elucidate a possible role of Hcy in the development of cognitive dysfunctions in PD. We compared Hcy, vitamin B12 and folate levels in 35 parkinsonian patients treated with L-dopa (14 with cognitive dysfunctions, 21 without cognitive impairment). Analysis of the data revealed that mean Hcy levels were significantly higher in the group with cognitive dysfunctions (21.2+/-7.4 vs. 15.8+/-4.4 micromol/L; p=0.0001), while there was no difference in age, sex, B12 and folate levels. In addition, logistic regression analysis showed that the risk of cognitive dysfunction progressively increased according to Hcy levels after correction for age, sex and B-vitamin status (odds ratio, 19.1; 95% CI, 1.5-241.4; p=0.02). Our results raise the possibility of a relationship between Hcy levels and cognitive dysfunctions in this group of L-dopa-treated PD patients. However, prospective studies on large cohorts of patients should be performed to clarify such an association.     

Elevated plasma homocysteine levels in L-dopa-treated Parkinson's disease patients with dyskinesias.

BACKGROUND: Elevated plasma homocysteine (Hcy) concentrations are associated with increased risk of systemic vascular diseases, Alzheimer's disease and vascular dementia. Several cross-sectional reports and two prospective clinical studies have recently reported elevated plasma Hcy levels in L-dopa-treated Parkinson's disease (PD) patients and Hcy has been proposed as a possible mediator for the development of long-term L-dopa motor complications (such as wearing off and on-off phenomena, and dyskinesias). The aim of the study was to elucidate a possible role of L-dopa-related hyperhomocysteinemia in the development of dyskinesias. METHODS: In this cross-sectional study we compared Hcy, B(12) and folate levels in 53 PD patients treated with L-dopa (29 with dyskinesias, 24 without dyskinesias). RESULTS: Mean plasma Hcy levels were higher in the group of PD patients with dyskinesias (19 vs. 15.4 micromol/L; T: 2.12; p=0.04). After taking into account potential confounding factors, analysis of the data revealed that the occurrence of dyskinesias progressively increased with plasma Hcy levels (relative risk 1.2, 95% CI 1.015-1.4; p=0.03). CONCLUSIONS: Our results raise the possibility that Hcy plays a role in the development of dyskinesias, through its toxic effects on both dopaminergic neurons and non-substantia nigra, non-dopaminergic neurons.     

Elevated gonadotropin levels in patients with Alzheimer disease

OBJECTIVE: To determine whether gonadotropin levels are elevated in patients with Alzheimer disease (AD). PATIENTS AND METHODS: We measured luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels from stored plasma samples from 284 patients seen at a tertiary care center. We also reviewed their medical charts to record age and estrogen use in the women. The primary aim of our study was to determine whether gonadotropin levels were elevated in 134 patients with AD compared with levels from 45 patients with frontotemporal dementia (FTD) and 105 cognitively normal controls. RESULTS: Although overlap between LH and FSH levels was considerable, LH (P=.046) and FSH (P=.007) were significantly elevated in estrogen-free women with AD (LH: median, 26.3 IU/L; interquartile range, 14.9-34.6 IU/ L; FSH: median, 62.0 IU/L; interquartile range, 45.9-78.5 IU/L) compared with normal controls (LH: median, 20.1 IU/L; interquartile range, 13.7-25.3 IU/L; FSH: median, 47.7 IU/L; interquartile range, 34.1-57.5 IU/L). Levels of LH were also significantly higher (P=.03) in estrogen-free women with AD compared with women with FTD (LH: median, 20.7 IU/L; interquartile range, 19.0-28.5 IU/L; FSH: median, 53.3 IU/L; interquartile range, 27.6-77.9 IU/ L). When we controlled for age, no differences in LH and FSH were observed in men with AD compared with normal controls. CONCLUSIONS: Gonadotropin levels are elevated in some patients with AD, ie, women not taking estrogen. Elevated gonadotropin levels may have a role in the production of amyloid-beta protein, which is related to formation of senile plaques. Therefore, elevated gonadotropin levels may be involved in the pathogenesis of AD.     

Kinetics of primary bile acids in patients with non-operated Crohn's disease

Abstract. The metabolism of cholic acid and cheno-deoxycholic acid was studied in seventeen patients with non-operated Crohn's disease, eleven ileitis and six ileocolitis patients. The turnover of cholic acid was significantly increased in patients with ileitis ( k = 2.0±1.13 days^-1; P <0.001) and ileocolitis ( k = 0.91±0.47 days^-1; P <0.005) as compared to normals ( k = 0.35±0.19 day^-1). Although chenodeoxycholic acid was better preserved in the enterohepatic circulation than cholic acid its turnover was also significantly faster in ileitis ( k = 0.81±0.56 days^-1; P <0.005) and ileocolitis patients ( k = 0.62±0.18 days^-1; P <0.01) than in normals ( k = 0.20±0.09 days^-1). The fractional turnover of cholic acid was related to the length of ileal involvement ( r = 0.761; P <0.001; n = 17). Patients with Crohn's ileitis tended to preserve normal fasting total bile acid pools by increased synthesis of primary bile acids and efficient absorption of deoxycholic acid and ursodeoxycholic acid by the normal colon. Patients with active ileocolitis had decreased total fasting pool sizes (2.62±1.83 mmol; P <0.001) as compared to normals (7.69±1.61 mmol). In these patients there was no increase in bile acid synthesis as compared to normals and secondary bile acids were absent from bile. It is concluded that the colon has an important role in maintaining the fasting pool size to a normal level in the presence of an interrupted enterohepatic circulation of bile acids due to ileal disease.     

Pharmacokinetics of mezlocillin in patients with hepatobiliary dysfunction

The pharmacokinetics of mezlocillin were investigated in 26 patients with alcoholic liver disease. Serum concentrations of mezlocillin were measured following intravenous administration of 3 g doses over 30 min. The mean peak serum concentration (+/- standard deviation) of mezlocillin at the end of infusion was 138.8 +/- 55.7 mg/l and the mean terminal half-life (T 1/2 beta) was 2.10 +/- 0.9 h. The 24 h urinary recovery of mezlocillin was 35.4 +/- 12.4% of the administered dose. Serum clearance was found to be inversely correlated with alkaline phosphatase and with total bilirubin. The T 1/2 beta was related to the following clinical measurements: age, SGOT and prothrombin time. This relationship suggests it may be prudent to adjust the dosage and the dosage interval of mezlocillin in patients with hepatobiliary dysfunction.     

Increased levels of typically fetal bile acid species in patients with hepatocellular carcinoma

The aim of this work was to investigate the reappearance during liver neoplasia of bile acids (BAs) species, which are unusual in healthy adults, but common in fetuses. Serum and urine samples were collected from patients with hepatocellular carcinoma (HCC; n=27), and for comparative purposes, with liver cirrhosis (n=49), liver metastasis (n=19), chronic viral hepatitis (n=11) and healthy volunteer (control group; n=26) groups. BAs were identified and measured by GC--MS. Hypercholanaemia was found in all groups of patients. In HCC, this was characterized by a marked increase in the chenodeoxycholate/cholate ratio in both serum and urine. Although increased levels of BAs, with hydroxylations at unusual positions, and oxo-BAs were found in HCC, these were not significantly different from those observed in other groups. However, BAs with a flat structure, i.e. Delta(4)-unsaturated- and 5 alpha- or allo-BAs, which were almost absent in healthy subjects, were markedly increased in the serum and urine of HCC patients. They were also detected, although in much lower amounts, in liver metastasis and liver cirrhosis, but not in viral hepatitis. Flat-BAs were better detected in urine than in serum. Urinary Delta(4)-unsaturated-BA output was significantly lower in patients with small tumours (<3 cm) compared with those with higher size tumours. No correlation between flat-BA output into urine and serum alpha-fetoprotein or total BAs was found. These results suggest that Delta(4)- and/or allo-BAs are particularly elevated in patients with HCC, which may be a potentially useful complementary, rather than alternative, marker for early detection of liver neoplasia.