Treatment of obstructive sleep apnoea in Samoa progressively reduces daytime blood pressure over 6 months

Background and objective:   While recent meta-analyses suggest that OSA elevates daytime blood pressure (BP), most studies have included patients with mild hypertension, so CPAP treatment has only reduced BP by 2–3 mm Hg. To determine the strength of the OSA–BP relationship, this study examined the effect of CPAP in a cohort where severe OSA and under-treated hypertension coexist.
Methods:   Baseline demographic and sleep study data were recorded in 221 consecutive patients referred for sleep studies in Samoa. OSA was treated with CPAP and BP recorded for 6–7 months in 180 patients. A subgroup of 64 patients, representative of the entire group, but with regular follow-up, is also described.
Results:   OSA was diagnosed in 218/221 patients; of those who commenced CPAP, 180 returned for follow-up at least once within 7 months. Following CPAP, BP decreased by 7.1/5.9 mm Hg at 1 month and 12.9/10.5 mm Hg at 6 months ( n  = 180, P  < 0.0001). In the 64 patients with regular follow-up, those with the highest baseline BP had the greatest fall in BP with CPAP; BP in the hypertensive subgroup (32/64) decreased 21.5/13.1 mm Hg at 6 months ( P  < 0.0001).
Conclusions:   Hypertensive OSA patients can exhibit large falls in BP with CPAP at 1 month, with further significant reductions at 3 and 6 months. Overall, the fall in BP was proportional to the initial elevation of the BP with many patients achieving normal BP at 6 months.     

Molecular epidemiology of hepatitis C in Australia

The aim of this study was to determine the distribution of hepatitis C virus (HCV) genotypes in Australian patients with hepatitis C and to identify factors associated with particular genotypes. Serum isolates of HCV-RNA were genotyped using a commercial oligonucleotide hybridization (line probe) assay. Relationships between demographic factors, mode of HCV transmission and HCV genotype were assessed by logistic regression analysis. Among 463 patients with hepatitis C, 425 tested positive for HCV-RNA and a single HCV genotype was identified in 420 cases. The patients' places of birth were Australia or New Zealand (62%), Asia (13%), Europe (12%), Mediterranean (6%), Middle East (6%) and other countries (<1%). The most common genotypes were type 1 (52%) or type 3 (32%); type 2 (9.3%), type 4 (5.5%) and type 6 (1.7%) were less common. Patients with genotype 1b were older (48 ± 13 years, P < 0.001) and patients with genotype 3 were younger than the remaining patients (37 ± 11 years vs 42 ± 12 years, P < 0.001). Among type 1 isolates, 1b was more common for patients born outside Australia compared with those born in Australia (50%vs 13%, P < 0.001) whereas non-1b subtypes were more common among Australian-born patients. Likewise, 21 of 23 (91%) patients with type 4 were from Egypt and six of seven (86%) with type 6 were from Vietnam. The relative importance of parenteral risk factors for HCV also varied according to geographic origin. Thus, a definite risk factor for HCV acquisition was identified in > 95% of Australian-born patients, but in only 33% of Asian or Mediterranean-born patients. Logistic regression analysis indicated that region of birth and risk factor (intravenous drug use or not) would allow 98% of type 4 cases and 76% of type 1b cases to be identified correctly. In summary, region of birth, patterns of migration over time and risk factors for transmission of HCV interact to determine the distribution of HCV genotypes in a multi-racial community like Australia.     

The mode of anti‐arthritic peptide delivery impacts on the severity and outcome of adjuvant induced arthritis

Aim: A synthetic nonapeptide (core peptide [CP]) was tested as a potential therapeutic agent for the treatment of acute onset arthritis. Differing modes of delivery (subcutaneous [SCI]vs. intraperitoneal [IP]) and lipid conjugation of CP were examined. Methods: Wistar rats aged 9–12 weeks were injected SCI in the tail with 1 mg of heat‐killed Mycobacterium tuberculosis (MTB) to bring about adjuvant induced arthritis. After development of arthritis (day 12), 6 mg of CP, 6 mg of CP‐lipid conjugate (LP), or 1.2 mg cyclosporin A (Csp; 3 mg/kg) in 100 µL of diluent were given SCI or IP for 4 consecutive days. Severity of arthritis was assessed by changes in body weight, paw thickness, paw and ankle width, and the total number of arthritic joints involved up to 7 days after the first onset of arthritis and the commencement of treatment. Results: Core peptide and LP given either SCI or IP were effective in the treatment of acute adjuvant induced arthritis. IP administration of LP was significantly better than that of control and CP‐treated rats (P < 0.05) when examined at two separate time points, day 4 and day 7, after commencement of treatment. The effectiveness of IP‐administered LP was comparable to cyclosporin. Conclusions: CP‐lipid conjugate and CP have a therapeutic benefit in the treatment of acute arthritis. The mode of delivery and lipid conjugation of CP influences the efficacy and outcome of arthritis.     

Perforated peptic ulcer in Hong Kong and New South Wales

Direct comparisons of ulcer perforation rates and trends between countries have not been made in the past. Data on hospital admissions for perforated peptic ulcer during 1 January 1979 to 31 December 1985 were collected in Hong Kong (5868 perforations) and New South Wales, Australia (1669 perforations). Age and sex specific rates per 100,000 population were calculated. In Hong Kong, annual duodenal ulcer and gastric ulcer perforation rates were 13-16 and under two per 100,000 population respectively. In New South Wales, the corresponding rates were between three and four and under two per 100,000 population, respectively. The male:female ratios for duodenal ulcer perforation were consistently about 5:1 in Hong Kong and 2:1 in New South Wales, and for gastric ulcer perforation about 2:1 and 1:1, respectively. The incidence of perforation increased with age, and there was a statistically significant rise, over time, in duodenal but not gastric ulcer perforation rates in persons aged over 60 years in New South Wales; similar trends were seen in Hong Kong. Thus duodenal ulcer perforation occurs five times more commonly in Hong Kong than in New South Wales and this is largely accountable for by the higher rates of duodenal ulcer perforation in Chinese than in Australian males. Such geographical differences can best be explained by the occurrence of multiple aetiological mechanisms in ulcer perforation. Furthermore, there appears to be an increased susceptibility and an appreciable rising trend for duodenal ulcer perforation to occur in the elderly.     

How much does alcohol contribute to the variability of hepatic fibrosis in chronic hepatitis C?

In order to determine the contribution of alcohol intake to the severity of hepatic fibrosis in patients with chronic hepatitis C, we studied associations between various levels of alcohol intake, other demographic variables and semiquantitative liver histology in 434 cases of chronic hepatitis C. Clinical, demographic and disease-related data were entered into a relational database. Liver histology was scored according to Scheuer. The average daily alcohol intake for the year preceding liver biopsy (recent exposure) and for earlier periods (past exposure) was categorized into five levels of intake. One-third of patients gave a history of alcohol intake that had exceeded 40g/day for at least 5 years. By univariate analysis, age, but not recent or past alcohol intake or other baseline variables, was associated with portal score (r=0.14, P= 0.004), fibrosis score (r= 0.46, P < 0.001), total Scheuer score (r= 0.35, P < 0.001), However, by multivariate analysis, age (P < 0.001), past (but not present) alcohol intake (P < 0.001) and birth in Egypt (P= 0.006) were independently associated with fibrosis score. Age, past alcohol and birth place in Egypt contributed 27% to total variance of the hepatic fibrosis score, while age alone accounted for 23%. Age also independently predicted portal activity (P=0.02) and total Scheuer score (P < 0.001), whereas past alcohol intake correlated with total Scheuer score (P= 0.002) but not with other histological indices. A separate multivariate analysis was performed on a more homogeneous subgroup of 196 patients who acquired hepatitis C by injection drug use. In this subgroup, age (P < 0.05) and past alcohol (P < 0.05) were independently associated with fibrosis score. In both the overall and subgroup analyses, there was a threshold level of past alcohol intake (>80g/day) beyond which the risk of fibrosis increased significantly. It is concluded that toxic levels of alcohol exposure for at least 5 years accentuate hepatic fibrosis in hepatitis C but the influence of alcohol appears to be minor compared with age and other variables and is exerted only at toxic levels of intake.     

Sequential changes in serum levels of individual bile acids in patients with chronic cholestatic liver disease

In order to determine the value of serum bile acids in predicting the course of chronic cholestatic liver diseases, we measured individual serum bile acids serially, using high-performance liquid chromatography, over a 4 year observation period in 12 patients with primary biliary cirrhosis and six patients with primary sclerosing cholangitis. The changes in individual serum bile acids and the ratios thereof, conventional liver tests and Child-Turcotte and Mayo scores were compared between survivors (n= 10) and patients who underwent liver transplantation for (n= 3) or died of the liver disease (n= 5). Patients with a serum total chenodeoxycholic acid concentration at study entry that exceded 15 μmol/L were 10 times more likely to die or need a liver transplant in the following 4 years than those with chenodeoxycholic acid levels < 15 μmol/L (P < 0.05). None of the other biochemical parameters or clinicopathological scores could similarly discriminate between the two groups at entry. Time-dependent analyses for the cholic acid/chenodeoxycholic acid ratio, serum total bilirubin and albumin concentrations and Child-Turcotte and Mayo scores were able to differentiate between primary sclerosing cholangitis patients who died or were transplanted and those who were not, whereas age of the patients and other parameters did not. The taurocholic acid /taurochenodeoxycholic acid ratio fell during progression of primary biliary cirrhosis but rose in temporal relationship with primary sclerosing cholangitis. This differential pattern of change was unique compared with other clinical and laboratory indices. In conclusion, serum chenodeoxycholic acid levels and the cholic acid /chenodeoxycholic acid ratio in both diseases were independent indices that allowed for the prediction of survival or the need for liver transplantation. These indices are worthy of further examination in a larger group of patients as prognostic criteria for chronic cholestatic liver disease and in the assessment of the efficacy of therapeutic interventions, including liver transplantation.     

Influence of clinicopathological variables on CYP protein expression in human liver

Drug metabolism is usually impaired in malnourished patients with decompensated cirrhosis, but the separate influence of clinicopathological variables, including nutritional status, on the expression of hepatic cytochrome P450 proteins has not been well characterized. We determined the hepatic content of CYP1A2, CYP2C8/10, CYP2E1 and CYP3A proteins in 71 subjects, 21 with histologically normal livers and 50 with chronic liver disease, and then tested for potential relationships between patient variables and individual CYP proteins by multivariate linear regression analysis. Variables analysed included nutritional status (determined by experienced clinicians), serum albumin and bilirubin concentrations, prothrombin time, the grade of ascites and hepatic encephalopathy, and the Child-Pugh score. Impaired nutrition and cachexia were associated with reductions of CYP2C8/10 levels of approximately 19 and 39%, respectively, relative to cases in which nutrition was replete. Similarly, CYP2E1 protein was reduced by approximately 13 and 26%, according to the apparent severity of nutritional impairment. In contrast, nutritional status did not contribute to variability in expression of CYP1A2 or CYP3A proteins. Of the clinicopathological variables analysed, only serum bilirubin was shown to have an independent influence on CYP protein content. Thus, elevated serum bilirubin concentrations were associated with significant declines in the contents of CYP1A2 and CYP2C8/10 but not CYP3A or CYP2E1. The mechanisms for the effects of nutritional status and serum bilirubin concentration on the levels of CYP proteins are unclear, but could be mediated by factors such as cytokines, dietary composition and alterations in the level of serum bile acids. Knowledge of the influence of clinicopathological factors and nutritional status on CYP expression should lead to more rational drug prescribing in patients with hepatic disease.     

Who should receive methadone maintenance?

The aim of this study was to evaluate the assessment policies of a regional unit established to process requests for entry to several long-term methadone maintenance programmes. The factors which led staff to reject an applicants request for methadone maintenance were retrospectively analysed from assessment records. Analysis indicated that the decision to reject applicants had been based on the judgement that they were not physically dependent on opioids; other factors favouring rejection included less involvement in crime, youth, and short duration of drug use. Eighty-four applicants who had either been rejected (n= 58) or failed to complete the assessment (n= 26) were followed. At follow-up, more than half of the subjects had entered methadone programmes, usually after a long delay. Four subjects had achieved a degree of stable abstinence. The remainder were continuing to use illicit drugs, or were in treatment or prison. Four subjects had died. We conclude that: (I) our criteria for excluding people from treatment were based on the perceived need to keep non-addicted people from maintenance treatment; and (2) such a policy in practice served to prolong the applicants' illicit drug use and delay their entry to treatment.