LAAM maintenance vs methadone maintenance for heroin dependence.

BACKGROUND: LAAM and methadone are both full mu opiate agonists and have been shown to reduce dependence on heroin when given continuously under supervised dosing conditions. LAAM has a long duration of action requiring dosing every two or three days compared to methadone which requires daily dosing. LAAM is not as widely available internationally as methadone, and may be withdrawn from the market following ten cases of life-threatening cardiac arrhythmias and an association with QT prolongation. OBJECTIVES: To compare the efficacy and acceptability of LAAM maintenance with methadone maintenance in the treatment of heroin dependence. SEARCH STRATEGY: We searched MEDLINE (January 1966 to August 2000), PsycINFO (1887 to August 2000), EMBASE (January 1985 to August 2000), and the Cochrane Controlled Trials Register (Issue 2 2000). In addition we hand searched NIDA monographs until August 2000 and searched reference lists of articles. SELECTION CRITERIA: All randomised controlled trials, controlled clinical trials and controlled prospective studies comparing LAAM and methadone maintenance for the treatment of heroin dependence and measuring outcomes of efficacy or acceptability were included. DATA COLLECTION AND ANALYSIS: Data on retention in treatment, heroin use, side-effects and mortality were collected by two reviewers independently. A meta-analysis was performed using RevMan. Discrepancies were resolved by consensus. MAIN RESULTS: Eighteen studies, (15 RCTs, 3 Controlled prospective studies) met the inclusion criteria for the review. Three were excluded from the meta-analysis due to lack of data on retention, heroin use or mortality. Cessation of allocated medication (11 studies, 1473 participants) was greater with LAAM than with methadone, (RR 1.36, 95%CI 1.07-1.73, p=0.001, NNT=7.7 (or 8)). Non-abstinence was less with LAAM (5 studies, 983 participants; RR 0.81, 95%CI 0.72-0.91, p=0.0003, NNT=9.1 (or 10)). In 10 studies (1441 participants) there were 6 deaths from a range of causes, 5 in participants assigned to LAAM (RR 2.28 (95%CI 0.59-8.9, p=0.2). other relevant outcomes, such as quality of life and criminal activity could not be analysed because of lack of information in the primary studies. REVIEWER'S CONCLUSIONS: LAAM appears more effective than methadone at reducing heroin use. More LAAM patients than methadone ceased their allocated medication during the studies, but many transferred to methadone and so the significance of this is unclear. There was no difference in safety observed, although there was not enough evidence to comment on uncommon adverse events.

Multimedia benchmarking analysis for three risk assessment models: RESRAD, MMSOILS, and MEPAS.

This paper is one in a series that describes results of a benchmarking analysis initiated by the Department of Energy (DOE) and the United States Environmental Protection Agency (EPA). An overview of the study is provided in a companion paper by Laniak et al. presented in this journal issue. The three models used in the study--RESRAD (DOE), MMSOILS (EPA), and MEPAS (DOE)--represent analytically-based tools that are used by the respective agencies for performing human exposure and health risk assessments. Both single media and multimedia benchmarking scenarios were developed and executed. In this paper, the multimedia scenario is examined. That scenario consists of a hypothetical landfill that initially contained uranium-238 and methylene chloride. The multimedia models predict the fate of these contaminants, plus the progeny of uranium-238, through the unsaturated zone, saturated zone, surface water, and atmosphere. Carcinogenic risks are calculated from exposure to the contaminants via multiple pathways. Results of the tests show that differences in model endpoint estimates arise from both differences in the models' mathematical formulations and assumptions related to the implementation of the scenarios.

The assessment of depth of anaesthesia in animals and man.

The assessment of the depth of anaesthesia in man has received much attention in recent years, following a number of reports of people being aware during surgery. A range of different measures have been suggested for determining the adequacy of anaesthesia in man, but such a critical assessment is rarely applied to laboratory animals. This article describes the methods used to assess anaesthetic depth in both man and animals, and compares the relative states of knowledge about anaesthetic depth in animals and man.

Epidemiology of inflammatory bowel disease.

Epidemiologic studies of inflammatory bowel disease indicate that these disorders occur in susceptible individuals, possibly due to genetic abnormalities, resulting in disturbance of bowel wall function. Environmental factor(s) exerting a primary effect at an early age, in most patients, cause the disease to manifest usually in teenagers or young adults. Secondary environmental factors may alter disease expression, severity, or influence relapse. Studies in identical twins provide the best evidence for the role of genetic factors in the cause of Crohn's disease. Changing trends in disease incidence (seen in many countries) provide strong support for environmental factors as playing a major influence in disease expression. We now require further laboratory and epidemiologic studies in family members at risk of disease, in migrants who move from low incidence areas to high incidence areas, and in area where Crohn's disease particularly is starting to appear. The clinician can play an important role by performing careful observations in patients with a view to uncovering new clues to disease etiology.

PIP: The epidemiology of the 2 main types of inflammatory bowel disease, Crohn's disease and ulcerative colitis, is updated in this review. The incidence of these diseases is about 3-20 new cases/100,000/year. Ulcerative colitis usually has a higher incidence, but Crohn's disease incidence is rising fast in the U.S., U.K., Denmark and Israel, catching up with the rates of ulcerative colitis. Incidence is moderate in Central Europe and Australia, and low in South America, Asia, and Africa. There are no proven links to climate, environmental factors, genetic markers, or transmissible agents; although infections, fiber, sugar and milk have all been proposed as possible causes. Epidemiological studies suggest that ulcerative colitis is more common in non-smokers, while Crohn's disease is 2-4 times more common in smokers. Symptom remission in Crohn's disease has been reported in women who stop taking oral contraceptive, while, on the contrary, both diseases have been reported are more prevalent in non-pill users. In any event the relative risk is less than 2, a weak association.

Relative incidence of Crohn's disease and ulcerative colitis in six Melbourne hospitals.

Information on the relative incidence of Crohn's disease and ulcerative colitis was obtained by a prospective investigation at six Melbourne teaching hospitals. One hundred and eleven patients who presented with chronic inflammatory bowel diseases between 1980-1981 were admitted to the study. Forty (36%) patients were diagnosed as having Crohn's disease and 63 (57%) patients as having ulcerative colitis. The type of chronic inflammatory bowel disease could not be determined in eight (7%) patients. These findings suggest that the relative frequency of Crohn's disease and ulcerative colitis in Melbourne hospitals is within the range that is reported for northern Europe and the United States.

Hepatic vein occlusion (Budd-Chiari syndrome): problems in diagnosis and management.

Seven patients demonstrating the difficulties in diagnosis and management of hepatic vein occlusion are presented. The syndrome may present in an acute form with upper abdominal pain, abdominal swelling, ascites and tender hepatomegaly or in a chronic form, mimicking cirrhotic ascites. The clinical features, predisposing factors, liver scan and liver biopsy may all suggest the condition, but hepatic venography is essential for diagnosis and as a preliminary to treatment. It is suggested that early side to side portacaval anastomosis is the current treatment of choice.

Long-term follow-up of patients with Crohn's disease. Relationship between the clinical pattern and prognosis.

In a study of 615 new patients with Crohn's disease consecutively diagnosed at the Cleveland Clinic between 1966 and 1969, 592 patients were observed (mean greater than 13 yr, minimum 7 yr), giving a follow-up rate of 96.3%. The original hypothesis was that initial anatomic involvement (the clinical pattern) bears directly on clinical course and prognosis. Disease sites were as follows: 246 ileocolic, 165 small intestine, and 181 colon/anorectal. Among patients with ileocolic disease, 225 (91.5%) had surgery. For the small intestine pattern, the operative incidence was 65.5%; for the colon/anorectal pattern, it was 58%. Operations were for specific reasons: internal fistula with abscess or intestinal obstruction for ileocolic pattern; intestinal obstruction for small intestine pattern; and severe perianal disease or toxic megacolon for colon/anorectal pattern. Complications among nonoperated patients included perianal fistulas and extraintestinal manifestations. No statistical correlation existed between type and duration of medical treatment and prognosis. Seventy-five deaths occurred (12.8%), 36 of which related directly to Crohn's disease. Even after many years, symptoms continued and quality of life tended to be suboptimal among operated patients. For nonoperated patients, the most favorable quality of life was experienced by those with segmental involvement of the colon or ileum. Poor prognosis correlated with ileocolic disease and presence of sepsis because of an internal fistula.

Recurrence after surgery in Crohn's disease. Relationship to location of disease (clinical pattern) and surgical indication.

Among 615 patients with Crohn's disease originally diagnosed at the Cleveland Clinic Foundation from 1966 to 1969, 592 have been followed (96%) for a mean of 13 yr. Of these, 438 had undergone operation. The purpose of this study was to determine how many of these patients had developed recurrences requiring another operation and to relate recurrences to the original anatomic location of disease (the clinical pattern) and surgical indication. Those patients with ileocolic disease had the highest recurrence: 53% compared with 45% for colonic and 44% for small intestinal patterns. Second recurrences were ileocolic pattern 35%, colon 34%, small intestine 38%. The estimated median time of recurrence was similar among these three groups. The presence of internal fistula or perianal disease as an indicator for surgery were associated with a higher likelihood of recurrence and a shortened estimated median time to recurrence. This study supports the concept of conservatism with regard to the management of these two complications for patients with Crohn's disease.

Treatment of reflux oesophagitis. A randomized, controlled evaluation of cimetidine.

Twenty-five patients were studied in an eight-week randomized controlled comparison of cimetidine and placebo in the treatment of reflux oesophagitis. Therapy with cimetidine (1.0 g/day), compared with placebo, did not produce a statistically significant beneficial effect as assessed by relief of heartburn, reduction in antacid use, endoscopic evidence of healing, histological signs of improvement, or response to the acid perfusion (Bernstein) test.

Alcohol unrelated hepato-biliary disorders in the alcoholic: the role of liver biopsy in determining the aetiology of liver disease.

Alcoholics with abnormal liver function tests are generally assumed to have one of the recognised patterns of alcoholic liver injury. This report described a group of nine patients who were initially thought to have alcoholic liver disease but were found on liver biopsy to have a variety of liver disorders unrelated to alcohol. Liver biopsy showed granulomatous hepatitis in three, primary biliary cirrhosis in two, and cholestasis of unknown cause, large duct biliary obstruction, haemochromatosis with secondary carcinoma and Budd-Chiari syndrome in one each. The histological changes observed in liver biopsy samples are believed to represent a chance occurrence of liver disease due to some agent other than alcohol and illustrates that forms of hepatic disease that affect the population at large can and do occur in heavy alcohol consumers.

Paracetamol self-poisoning: diagnosis, management, and outcome.

Over a four-year period, 103 patients presented to St Vincent's Hospital, Melbourne, after poisoning themselves with paracetamol. Most of them were young adults who suffered temporary emotional or social distress. There was severe liver damage in four patients who presented, or were recognised, 24 hours or more after the ingestion of paracetamol. The absence of severe liver damage in the remaining 99 patients was attributed to early intervention with specific therapy with orally administered methionine or intravenously administered N-acetylcysteine. We describe a rapid plasma paracetamol assay which can aid in the diagnosis and management of this problem. All physicians should be aware that paracetamol-induced hepatic necrosis is not clinically apparent for two to three days, and that it can be prevented by early specific treatment.

The influence of diethylmaleate on the biliary excretion of infused sulphobromophthalein sodium and its glutathione conjugate in guinea-pigs.

1. Hepatic sulphobromophthalein (BSP) transport was studied in guinea-pigs pretreated intraperitoneally with 0.7 ml of diethyl maleate to depress hepatic glutathione levels. 2. Diethyl maleate depressed the hepatic transport of infused conjugated BSP from hepatocytes into bile without influencing hepatic uptake. 3. Unconjugated BSP transport was also depressed markedly as a result of (a) a reduction in the intrahepatic conjugation of BSP with glutathione and (b) suppression of conjugated BSP excretion.

The metabolic consequences of jejunoileal bypass for obesity.

Twenty-one female patients studied between six and 12 months following a jejunoileal bypass procedure for obesity were found to have a wide variety of metabolic disturbances. Hepatic histological abnormalities were common and included liver cell necrosis and inflammation in nine patients and hepatic fibrosis in five. Liver function tests were no guide to the degree of hepatic impairment. Vitamin B12 malabsorption occurred in seven patients, in six probably as a result of bacterial intestinal overgrowth; three of these six patients had the most serious hepatic morphological changes. Malabsorption rather than poor oral intake of food appeared to account for continued postoperative weight loss in the majority of patients.