Validation of methylmercury determinations in aquatic systems by alkyl derivatization methods for GC analysis using ICP-IDMS.

Isotope dilution mass spectrometry (IDMS), using an inductively coupled plasma quadrupole mass spectrometer (ICPMS) and a species-specific methylmercury spike was applied to validate the commonly used GC method for methylmercury (MeHg+) determination, which is based on the formation of volatile methylethylmercury by derivatizationwith NaBEt4. The spike compound, Me201Hg+, was synthesized by reaction of 201Hg-enriched mercury chloride with methylcobalamin. By analyzing different environmental aquatic samples, it was found that in most cases, transformation of MeHg+ into elemental mercury (Hg0) took place. From investigations of synthetic solutions, it could be followed that halide ions are responsible for this transformation process. Chloride and bromide converted MeHg+ into Hg0, whereas iodide caused transformation into Hg2+ and Hg0. It could also be shown that transformation of MeHg+ took place only during the derivatization step. In contrast to ethylation, propylation by NaBPr4 did not cause any transformation; however, accurate results of MeHg+ determinations could be obtained by propylation as well as by ethylation when GC/ ICP-IDMS was applied. This work demonstrates the great power of isotopically labeled element compounds for the validation of element speciation methods and for species-specific IDMS analyses.

A new source of drug-induced acute pancreatitis: codeine.

A variety of drugs have been reported to cause acute pancreatitis during the past 40 years. We report the first series of four cases of acute pancreatitis related to codeine ingestion. Four patients (three female, mean age 50.2 yr) presented with clinical, biochemical, and radiological evidence of acute pancreatitis. All four had ingested a therapeutic dose of codeine 1-3 h before the onset of abdominal symptoms. Unintentional rechallenge occurred in three cases and was followed by recurrence of acute pancreatitis in all three. All patients made a full recovery. All four patients had had a previous cholecystectomy. The likely underlying pathophysiological mechanism is codeine-induced spasm of the sphincter of Oddi combined with sphincter of Oddi dysfunction related to a previous cholecystectomy. Codeine ingestion leads to acute pancreatitis in some individuals. Previous cholecystectomy seems to predispose to codeine-induced pancreatitis.

Chondrex (YKL-40), a potential new serum fibrosis marker in patients with alcoholic liver disease.

OBJECTIVES: Chondrex (YKL-40) is a mammalian member of a protein family that includes bacterial chitinases. The pattern of its expression in certain tissues such as human liver or cartilage suggests a function in remodelling or degradation of extracellular matrix. The purpose of this study was to assess whether circulating YKL-40 might be a serum fibrosis marker in alcoholics. METHODS: Plasma YKL-40 was determined in 146 consecutive heavy drinkers (106 men, 40 women; mean age, 49.2 +/- 9.0 years). Liver biochemical parameters and serum fibrosis markers such as hyaluronate were also measured. Fibrosis and inflammation in liver biopsy were evaluated using a semi-quantitative scoring system. RESULTS: Plasma YKL-40 increased in parallel with the severity of fibrosis (P<0.00001). YKL-40 also increased in the presence of hepatic inflammation (P<0.01). Receiver operating characteristic curves of Chondrex revealed that a threshold of 330 microg/l gave a specificity of 88.5%; however, the sensitivity was only 50.8%. Only 11.5% of patients without severe fibrosis displayed a Chondrex plasma level above this threshold. A positive correlation was found between Chondrex and hyaluronate (r=0.40, P<0.0001), and a negative correlation was shown between Chondrex and the prothrombin index (r=-0.37, P<0.0001). CONCLUSIONS: The severity of liver fibrosis is associated with elevated circulating Chondrex levels. The overlap in YKL-40 values prevents use of Chondrex in a screening programme. High levels of Chondrex (above 330 microg/l) are predictive of severe liver fibrosis. Increased plasma YKL-40 may reflect the remodelling of liver fibrosis in alcoholics.

Non invasive prediction of severe fibrosis in patients with alcoholic liver disease.

OBJECTIVES: The aim of this study was to assess the diagnostic accuracy of noninvasive markers of liver fibrosis in alcoholic liver disease. PATIENTS AND METHODS: Fifty-four clinical and biochemical parameters including serum fibrosis markers (hyaluronate and transforming growth factor beta1) were analyzed in 146 consecutive heavy drinkers (106 men, 40 women; mean age 49.2 years). Following liver biopsy, fibrosis was evaluated using a semi-quantitative scoring system (no fibrosis (0) to severe fibrosis (3 + )). Multivariate analysis was performed to determine the markers that were best correlated with the fibrosis score. RESULTS: Fifty-nine patients (40.4 %) had severe fibrosis (3 +) while 87 (59.6 %) had no fibrosis or moderate fibrosis (0 to 2 +). In multivariate analysis, serum hyaluronate and the prothrombin index were the best markers for the prediction of severe fibrosis. Hyaluronate and the prothrombin index had a diagnostic accuracy of 91.1 % and 89.7 %, respectively in the whole population. Finally, a significant negative correlation was found between hyaluronate and the prothrombin index (r =- 0.86, P <0.0001). CONCLUSIONS: Using only hyaluronate and the prothrombin index, 9 out of 10 alcoholic patients can be correctly classified according to the severity of liver fibrosis.

Ascending colonic variceal bleeding: utility of phase-contrast MR portography in diagnosis and follow-up after treatment with TIPS and variceal embolization.

The authors describe the discovery of ascending colonic variceal veins via celiomesenteric diagnostic angiography following a bout of melena in a 44-year-old woman. Magnetic resonance imaging, including phase-contrast MR venography, allowed visualization of the portal and systemic veins immediately after the initial angiograms. The hemorrhagic episode did not resolve until after transjugular intrahepatic shunt insertion and selective variceal embolization through the shunt. At 1 week-, 3 months-, and 6 months post treatment, follow-up MR venography no longer revealed the presence of colonic varices. Colonoscopy at 6 months was normal and the patient did not have any further episodes of bleeding until a liver transplantation was performed after 9 months.

Endoscopic bilateral metal stent placement for malignant hilar stenoses: identification of optimal technique.

BACKGROUND: The aim of this study was to identify factors that facilitate bilateral insertion of metal stents in malignant hilar stenoses, for which plastic stents often result in incomplete drainage and subsequent cholangitis. METHODS: Between January 1994 and April 1998, we collected 45 cases of advanced (Bismuth stage II or higher) hilar malignant stenoses. The insertion technique was progressively modified and the success rate in the early period (1994 to 1995) was compared with that of a later period (1996) and the most recent period (1997 to 1998). RESULTS: Overall success rate was 73.3% (33 of 45). The success rates for the three periods were 50%, 67%, and 88% (p = 0.008), respectively. Cholangitis occurred in 3 of the patients with unilateral stents compared with 1 with bilateral stents. CONCLUSION: We have described a technique for endoscopic insertion of bilateral metallic stents for malignant hilar stenoses that results in high (>88%) and reproducible success rates.

Evaluation of family health education to build social support for long-term control of high blood pressure.

Sustaining patient motivation for long-term adherence to drug therapies remains a substantial problem for physicians, other health care providers, the patients themselves, and their families. Other therapeutic requests such as dietary changes and weight control may be even more difficult to maintain than taking pills. As part of a controlled experimental design implemented in an outpatient teaching hospital, an educational program was implemented to improve family member support for medical compliance among hypertensive patients. Family members were interviewed, counseled, and provided with a booklet for the purpose of educating and involving them in the home management of high blood pressure. The booklet identified ways the family member could assist the patient with medication compliance, appointment keeping, as well as diet and weight control. These items were identified and recorded as behavioral objectives in the booklet. Patients were followed for three years to assess long-term outcomes. Results showed a strong statistically significant difference between the experimental and control groups, with the experimental group demonstrating higher levels of appointment-keeping behavior, weight control, and BP under control (all p values less than .001). Analysis of the main effects of the educational program demonstrated that the family member support intervention accounted for the greatest decrease in diastolic blood pressure variability, R2 = .20, p less than .001.