Robert Batey

Computer assisted quantitation of terminal hepatic vein connective tissue in the rat

Summary Computer assisted image analysis has been used to quantify the cellular and extracellular connective tissue component of rat liver terminal hepatic venules, in control animals and those exposed to 40% ethanol in drinking water. A significant relationship existed between the size of the terminal hepatic venule and the amount of connective tissue it contained in 14 of 15 controls and 17 of 18 ethanol exposed rats. Thickening of the terminal hepatic vein wall assessed to be present in ethanol treated rats by direct observation was confirmed by image analysis in all cases (p<0.01). Significant differences between treated and control livers (p<0.05) were detected by image analysis when not apparent to human observers. Sensitive quantitative assessment of terminal hepatic vein wall thickening was thus achieved by computerized analysis of liver sections.

Ethanol-related liver injury in the rat: a model of steatosis, inflammation and pericentral fibrosis

BACKGROUND/AIMSnWhile several animal models exist for the study of ethanol heptotoxicity, they are limited in their applicability. This paper describes a relatively simple rat model of alcohol-related liver injury.nnnMETHODSnEthanol was supplied in the drinking water in a concentration of 40% v/v for up to 29 weeks. Animals are concurrently supplied a chow diet which provides adequate protein and choline for normal growth. Total fat intake is low (7% of consumed calories).nnnRESULTSnHistological changes of steatosis, inflammation, hepatocyte necrosis and pericentral sclerosis were evident in ethanol-treated rat livers. Littermate controls with and without pair-feeding had normal livers. Electron microscopy revealed abnormal mitochondria and a marked proliferation of smooth endoplasmic reticulum in livers of animals fed ethanol. Biochemical analysis revealed that levels of hepatic-free choline were similar in treated and pair-fed control rats. There was an expected increase in the activity of the microsomal enzyme cytochrome P450 2E1 in ethanol-fed rats.nnnCONCLUSIONSnThe model provides a convenient method for the production of alcoholic liver injury, and it may be useful for the study of the pathogenesis of ethanol-related liver disease.

The use of serum methadone levels in patients receiving methadone maintenance

Trough serum methadone concentration was measured in 43 patients under treatment for heroin addiction and complaining of withdrawal symptoms. Low serum levels were noted only in patients taking very low doses and in 10 patients who were concomitantly using enzyme‐inducing drugs. The 27 patients in the maintenance program who had trough levels greater than 100 ng/ml were given no dose increase and were followed up prospectively. Alternate explanations for the patients symptoms were well accepted in almost all cases, and subsequent performance in the treatment program appeared to be independent of serum level. We conclude that a trough serum level of 100 ng/ml is adequate for effective methadone maintenance. Measurement of serum levels can be a valuable intervention in patients with difficulties.

Concordance between urinalysis results and self-reported drug use by applicants for methadone maintenance in Australia

This study examined concordance between self-reported drug use and urinalysis data among 341 applicants for methadone treatment in Sydney, Australia. Rates of under-reporting of use of specific drugs were low (0% to 10%). Irregular drug use, short half-life of some abused drugs, and relatively low sensitivity of the TLC assay procedure led to most detected drugs being found in only one of two urine samples collected. Subjects reported having recently used nearly twice as many drugs as were detected in their urine. Agreement (kappa) between self-report and urinalysis results was in the fair to good range for most drugs. None of the six predictors of misreporting examined were found to be of practical value.

A 40 month follow‐up of pregnant drug using women treated at Westmead Hospital

A 40 month follow-up of 84 women admitted to a study of the outpatient management of pregnant heroin users is reported. Fifty-eight of the patients were on methadone at the time of their delivery while a further 26 remained on heroin at delivery. The whereabouts of 61 patients were identified at the time of follow-up but only 46 consented to interview. Twenty-three could not be traced even utilising the services of the Departments of Corrective Services and Community Services. The general health of mothers and babies was reported as good to excellent and only one child was in the care of the State. Many patients on methadone at delivery had exited the programme whereas those on heroin at delivery were likely to be on methadone programmes at follow-up. A majority of all patients had had no new legal charges laid in the 12 months preceding the interview and if any charges had been laid they were likely to be traffic offences. Drug use, on the other hand, continued to be a problem even in those on methadone programmes. Up to 75% of patients in one group reported intermittent use of heroin and other drugs and these self reports were confirmed by urine testing. The data suggest that methadone does lead to a reduction in criminal activity and in daily drug usage but it does not completely abolish drug seeking behaviour. Overall, the results suggest that the use of methadone is safe for mother and baby and it has positive benefit in the management of pregnant drug users.

Changing prevalence of hepatitis B virus in urbanized Australian aborigines.

Serological surveys of desert or rural Australian Aboriginal settlements report up to 85% positivity for hepatitis B virus (HBV) markers. We report the results of two cross‐sectional HBV surveys carried out 5 years apart in the bi‐racial town of Condobolin, New South Wales (population 3086; 14% Aborigines).

A 12-month prospective comparison of court-diverted with self-referred heroin users

Forty-seven heroin users referred by the Drug and Alcohol Court Assessment Programme (DACAP) were compared with 45 self-referred heroin users at 12 months post-presentation. Data at presentation indicated distinct subpopulations were generated by each referral source. Differences were recorded in age, heroin use, marital status, educational level, employment history and age of onset of anti-social behaviour. The DACAP scheme exerted an earlier health intervention effect in a sample experiencing dysfunction in other areas, principally legally and socially. Prospective data demonstrated that both samples reported significant reductions in the proportion using heroin. Differences between samples evident at presentation were expressed prospectively, in rates of employment, incarceration and involvement in methadone maintenance programmes. The limitations of diverting clientele from the legal system to the treatment system is discussed in light of these results.

A Placebo Controlled Trial of Clonidine in the Outpatient Management of Heroin Withdrawal

We report the outcome of thirty-one patients, entered in a double blind controlled trial of clonidine in the outpatient management of heroin withdrawal. All study patients were monitored on a daily basis and their treatment regime was modified to control symptoms experienced during withdrawal. Symptoms and signs were recorded daily. Clonidine was no more effective than placebo in achieving a successful withdrawal although symptoms were less severe in those patients who received the active drug. The study design engendered anxiety in all patients and this may have decreased the efficacy of the treatment regime. Further studies of clonidine in the management of heroin withdrawal in a variety of settings are warranted.

Interferon alfa-2b for chronic active hepatitis C: Interim results of an australian trial

Abstract •■ Interferon produced a complete response in about 70% and a partial response (≥25% reduction ALT) in the remainder of patients treated with Interferon alfa-2b. •■ Spontaneous, complete or partial resolution of ALT abnormality did not occur in untreated patients. •■ The fall in serum ALT reflects reduced necroinflammation in liver biopsy. •■ Six months after interferon, complete remission was sustained for 2 months or more in 40% of patients. •■ The onset of relapse was often associated with acute hepatitis of greater severity than pretreatment illness.

Practical issues in the methadone management of pregnant heroin users

Methadone management of pregnant heroin-using patients has become a standard approach to this particular population of patients. This paper discusses the establishment and running of an out-patient stabilization programme and highlights areas of difficulty experienced in this exercise. Guidelines are suggested for those who wish to establish such a service in the future.