Alcohol consumption patterns and predictors of use following liver transplantation for alcoholic liver disease.

For patients who receive a liver transplant (LTX) for alcoholic liver disease (ALD), investigators are focusing beyond survival to determine specific alcohol use outcomes. Studies suggest the use of alcohol ranges from 8 to 22% for the first post-transplant year with cumulative rates reaching 30 to 40% by 5 years following transplantation. Yet while investigators are interested in determining specific rates of alcohol use and predictors of use, only three studies since 1990 have been prospective. In 1998, we began a prospective study of post-LTX alcohol consumption in ALD recipients using multiple repeated measures of alcohol use. After 5 years of follow-up, we found that 22% had used any alcohol by the first year and 42% had a drink by 5 years. By 5 years, 26% drank at a heavier use (binge) pattern and 20% drank in a frequent pattern. In a univariate model, predictors of alcohol use included pre-transplant length of sobriety, a diagnosis of alcohol dependence, a history of other substance use, and prior alcohol rehabilitation.     

Tobacco use following liver transplantation for alcoholic liver disease: an underestimated problem.

Alcohol and tobacco use commonly co-occur, with at least 90% of those with an alcohol problem also using tobacco. Thus, 3 years ago when we discovered higher rate of late deaths due to lung and oropharyngeal cancer in patients who had received a transplant for alcoholic liver disease (ALD), we hypothesized that these patients were continuing to expose themselves to tobacco after liver transplantation (post-LTX) and that this behavior was increasing their risk for cancer. We subsequently began a prospective investigation of post-LTX tobacco use in patients having undergone LTX for ALD (n = 172). For 33 recipients we had data starting from our first assessment at 3 months post-LTX and for this subgroup we report on the details of the timing of tobacco use resumption and the redevelopment of nicotine addiction. We found that on average more than 40% are smoking across all time periods. ALD recipients resume smoking early post-LTX, increase their consumption over time, and quickly become tobacco dependent. These data highlight an underrecognized serious health risk for these patients and demonstrate our need for more stringent clinical monitoring and intervention for tobacco use in the pre- and post-LTX periods.     

Inhibition of human benzylamine oxidase (BzAO) by analogues of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)

A sensitive assay for human plasma BzAO, involving the conversion of 14C-benzylamine to 14C-benzaldehyde, was developed. MPTP and several of its analogues were found to be competitive inhibitors of the enzyme. Ki values for the MPTP analogues in the presence of human plasma BzAO were determined. The analogues had a different rank order of inhibition of human plasma BzAO compared with the rank order of inhibition of bovine plasma BzAO found previously. MPTP and 1-methyl-4-(2-methylphenyl)-1,2,3,6-tetrahydropyridine (2'-CH3-MPTP), which are potent nigrostriatal toxins, were weak inhibitors of human plasma BzAO.     

Suppression of canine antral gastrin secretion by urine

Distention of the gastric antrum with an alkaline fluid normally results in the secretion of gastrin. Following gastrocystoplasty in humans, however, hypergastrinemia has not been observed. We explored the possibility that a component of urine may suppress antral gastrin activity in the dog. Partial cystectomy and antral transposition to the bladder (ATB) was performed in five animals and antral transposition to the colon (ATC) was performed in five other dogs to serve as a hypergastrinemic controls. At four and eight weeks after surgery the mean serum gastrin levels in the ATC dogs were significantly greater than the mean preoperative levels (p less than 0.05). In contrast, at four and eight weeks after surgery the mean serum gastrin levels in the ATB animals were significantly less than the mean preoperative levels (p less than 0.05). The antral G-cell density as determined by immunohistochemical study at eight weeks after surgery was greater than normal in the ATC dogs but less than normal in the ATB dogs; but the differences did not achieve statistical significance. In another series of experiments using four other dogs a 4% aqueous peptone solution and a 4% peptone solution in concentrated dog urine were instilled into exteriorized antral pouches. The mean serum gastrin levels at 60 and 90 minutes after instillation of the former were significantly increased (p less than 0.05), but there was little or no change after instillation of the latter. Urine, or a component of urine, appears to suppress canine antral gastrin secretion and may explain the absence of hypergastrinemia following gastrocystoplasty in humans.     

Comparison of Methodologies for Calculating Quality Measures Based on Administrative Data versus Clinical Data from an Electronic Health Record System: Implications for Performance Measures

New reimbursement policies and pay-for-performance programs to reward providers for producing better outcomes are proliferating. Although electronic health record (EHR) systems could provide essential clinical data upon which to base quality measures, most metrics in use were derived from administrative claims data. We compared commonly used quality measures calculated from administrative data to those derived from clinical data in an EHR based on a random sample of 125 charts of Medicare patients with diabetes. Using standard definitions based on administrative data (which require two visits with an encounter diagnosis of diabetes during the measurement period), only 75% of diabetics determined by manually reviewing the EHR (the gold standard) were identified. In contrast, 97% of diabetics were identified using coded information in the EHR.The discrepancies in identified patients resulted in statistically significant differences in the quality measures for frequency of HbA1c testing, control of blood pressure, frequency of testing for urine protein, and frequency of eye exams for diabetic patients. New development of standardized quality measures should shift from claims-based measures to clinically based measures that can be derived from coded information in an EHR. Using data from EHRs will also leverage their clinical content without adding burden to the care process.     

Inefficient delivery of yeast cells as an explanation for reduced plating efficiency of Candida albicans.

The plating efficiency for fungal yeast cells is usually less than that expected from microscopic counts, and a number of explanations for this phenomenon have been proposed. The present study was undertaken to explore possible reasons for reduced plating efficiency of Candida albicans. Explanations that we evaluated and found unlikely included: ineffectiveness of different culture media and/or incubation temperatures for growing colonies, insufficient area of the plate available for expression of individual colonies, production of microcolonies, and inaccurate counting of the organisms in the inoculum. An assay for delivery of the inoculum into tissue culture plate wells indicated that reduced delivery of the organisms accounted for lower than expected plating efficiency. C. albicans yeast cells grown under low glucose conditions and expected to have reduced adhesiveness were found to have higher values for both delivery and plating efficiency in our assays. In summary, our results indicate that reduced plating efficiency for C. albicans under the conditions used for these experiments is best explained by the loss of some yeast cells during preparation of the inocula or delivery of the yeast cells onto the plates.     

Fasciolopslasis--a re-emerging infection in Azamgarh (Uttar Pradesh)

Fasciolopsiasis is endemic in the far east. In India, there have been a few reports of the infection, prior to the 1990's. We report two cases from Azamgarh district of Uttar Pradesh. Both the cases were from nearby villages where water chestnuts are cultivated. These may be a source of infection. Pigs are commonly observed in these areas and and may be the source of ova. The only missing link is the finding of infected snails. Presence of at least three cases (one reported earlier) in the area indicates the potential for the infection to re-emerge. Further epidemiological studies are needed to analyse the various ecological factors of transmission. Fasciolopsiasis is endemic in China, Taiwan, Vietnam and Thailand. In India, (Fascilopsis buski) infections in man have been reported earlier from Assam, Maharashtra, Tamil Nadu and parts of Uttar Pradesh. However, to the best of our knowledge, no such reports have been made since 1990's. We herewith report two recent cases from district Azamgarh, Uttar Pradesh (U.P.), India. Factors, such as cultivation of water chestnuts, presence of snails as intermediate hosts and pigs as definitive host in this geographical area seem to be suggestive of an endemic focus and thus needs further epidemiological survey for preventive and control measures, at the earliest.     

Enteric pathogens and their isolation at a cancer hospital in Pakistan

Diarrhoeal diseases remain a major cause of mortality and morbidity in developing countries. However, due to lack of funds, supply problems and some inexperience, some laboratories have difficulty identifying a causative agent in stool samples. In the year following the opening of the Shaukat Khanum Memorial Cancer Hospital and Research Centre in Lahore, Pakistan, the microbiology department had not isolated a single enteric pathogen. From January 1996, new culture techniques were introduced, with a resulting increase (10%) in identification of these pathogens. In addition, the introduction of formol-ether concentration made a significant contribution to the number of intestinal parasites seen. This report demonstrates how simple microbiology methods made a difference to the running of the department and, ultimately, to the patients.     

The GAA triplet-repeat sequence in Friedreich ataxia shows a high level of somatic instability in vivo,with a significant predilection for large contractions

Friedreich ataxia is commonly caused by large expansions of a GAA triplet-repeat (GAA-TR) sequence in the first intron of the FRDA gene. We used small-pool PCR to analyze somatic variability among 7190 individual FRDA molecules from peripheral blood DNA of subjects carrying 12 different expanded alleles, ranging in size from 241 to 1105 triplets. Expanded alleles showed a length-dependent increase in somatic variability, with mutation loads ranging from 47% to 78%. We noted a strong contraction bias among long alleles (>500 triplets), which showed a 4-fold higher frequency of large contractions versus expansions. Some contractions were very large; of all somatic mutations scored, approximately 5% involved contractions of >50% of the original allele length, and 0.29% involved complete reversion to the normal/premutation length (< or =60 triplets). These observations contrast sharply with the strong expansion bias seen in expanded CTG triplet repeats in myotonic dystrophy. No somatic variability was detected in >6000 individual FRDA molecules analyzed from 15 normal alleles (8-25 triplets). A premutation allele with 44 uninterrupted GAA repeats was found to be unstable, ranging in size from 6 to 113 triplets, thus establishing the threshold for somatic instability between 26 and 44 GAA triplets. Analysis of an additional 7850 FRDA molecules from serially passaged lymphoblastoid cell lines carrying nine expanded alleles (132-933 triplets) showed very low mutation loads, ranging from 0% to 6.2%. Our data indicate that expanded GAA-TR alleles in Friedreich ataxia are highly mutable and have a natural tendency to contract in vivo, and that these properties depend on multiple factors, including DNA sequence, triplet-repeat length and unknown cell-type-specific factors.