Modulation of cholinergic contractions of airway smooth muscle by cathinone: potential beneficial effects in airway diseases.

Infusion of khat leaves is an African traditional remedy used to treat airway diseases. The beneficial effects of khat are thought to be due to the activity of its main active component, cathinone. Cathinone inhibited electric field stimulation-induced acetylcholine release and the contractions of smooth muscle, which could be responsible for the beneficial effects seen in airway disease. The mechanism of action of this natural product appears to be via the activation of both pre-junctional alpha(2) adrenergic and 5-hydroxytryptamine 7 receptors. The present novel study describes how cathinone modulates airway tone, and may go some way to explaining the traditional use of khat as a remedy for the alleviation of respiratory disease symptoms. In conclusion, cathinone may have beneficial effects in airway diseases with heightened cholinergic tone. There is some rationale for follow-up of these observations, given previous experience of other traditional remedies being developed for therapeutic use.

Khat (Catha edulis): health aspects of khat chewing.

Catha edulis Forsk leaves (khat) are chewed daily by a high proportion of the adult population in Yemen for the mild stimulant effect. Cathinone is believed to be the main active ingredient in fresh khat leaves and is structurally related and pharmacologically similar to amphetamine. The habit of khat chewing is widespread with a deep-rooted sociocultural tradition in Yemen and as such poses a public health problem. The objective of this literature review was to examine studies on khat, particularly human studies, with special reference to its effect on the central nervous system, cardiovascular, digestive and genitourinary systems, oral-dental tissues, diabetes mellitus and cancer.

Discontinuation of pegylated interferon plus ribavirin in patients who are not responding to therapy -- patients' views of early cessation of therapy.

BACKGROUND: Current therapy for chronic hepatitis C infection involves a course of pegylated interferon and ribavirin. Patients who do not show a virological response after 12 weeks of therapy have a low probability of sustained virological response and it is therefore recommended that such patients stop treatment. AIM: To assess patients' views of early treatment cessation. METHODS: We conducted a open-labelled study in three UK centres, in which patients with biopsy-proven chronic hepatitis C requiring therapy were offered the choice of a full course of therapy with 40 kDa pegylated interferon-alpha 2a plus ribavirin (24 or 48 weeks depending on viral genotype) or early cessation if therapy had failed after 12 weeks. RESULTS: Ninety-five participants were enrolled and the majority (69%) did not wish to discontinue therapy even if it had low probability of success. In this unselected UK population, very few patients (4%) did not achieve an early virological response with the 40-kDa pegylated interferon-alpha 2a plus ribavirin and two of the four early virological non-responders decided to continue therapy. CONCLUSION: Early discontinuation of 'ineffective' anti-viral therapy may prove less popular with patients than with health care providers, and further patient-directed education regarding the cost-effectiveness of therapy will be needed if early discontinuation of unsuccessful therapy is to be accepted by patients.

The assay of microsomal epoxide hydrolase in normal and pathological human liver.

Samples of normal and pathological human liver were assayed for microsomal epoxide hydrolase activity using the chlorinated epoxide HEOM as substrate. The enzyme activity in liver samples from normal patients was 72.3 +/- 9.8 nmoles mg protein-1.min-1, which is comparable to the highest values recorded in mammals, and much higher than those found in rats and mice. A microassay procedure was developed to enable the estimation of activity in needle biopsy samples (5-20 mg), obtained from patients with normal and diseased livers. Three epileptic patients who had received regular doses of phenobarbitone and/or phenytoin showed activities significantly higher than those found in all other samples (P less than 0.01). These appeared to be examples of enzyme induction. Assays were also performed on samples from six patients with alcohol-related liver disease and one patient with hepatocellular carcinoma. The role of epoxide hydrolase in the metabolism of carcinogenic epoxides is discussed in relation to these findings.

Khat chewing delays gastric emptying of a semi-solid meal.

BACKGROUND: The leaves of Khat are chewed for their central stimulant effect, but their use may cause anorexia and constipation. METHODS: Gastric emptying of a radio-labelled semi-solid meal was measured in 12 healthy volunteers on two occasions a week apart. Subjects chewed either Khat leaves (Catha edulis) or lettuce for 2 h before the study. RESULTS: Gastric emptying was significantly (P < 0.02) prolonged after chewing Khat compared with lettuce. CONCLUSION: The sympathomimetic action of cathinone in Khat may cause the observed delay in gastric emptying.

Comparison of the Trucut and Surecut liver biopsy needles.

The Trucut and Surecut liver biopsy needles have been compared in a prospective randomised study. Although the Surecut specimens were longer and heavier they tended to fragment during processing. Trucut specimens were subject to less artefact and were rated more highly by the histopathologist. However, the majority of biopsies obtained by both needles were satisfactory for diagnostic purposes.

Hazardous and harmful drinking: a comparison of the AUDIT and CAGE screening questionnaires.

BACKGROUND: Hazardous and harmful use of alcohol remains a public health concern, and many general hospital admissions are alcohol-related. AIM: To compare the CAGE and Alcohol Use Disorders Identification Test (AUDIT) questionnaires in screening general medical admissions for harmful or hazardous drinking. DESIGN: Prospective questionnaire-based study. METHODS: Both questionnaires were administered, and demographic data collected. RESULTS: One hundred and three patients were included. Of these, 36% were identified by the AUDIT to be drinking hazardously or harmfully, and 22% were identified as CAGE cases. All CAGE cases were also AUDIT cases. DISCUSSION: As the CAGE and the AUDIT are designed to identify different populations, it is not surprising that significantly fewer cases were identified using the CAGE. The AUDIT identifies not just the harmful drinkers detected by the CAGE, but also hazardous drinkers, who have not yet reached that level of harm. As drinkers at an earlier stage may respond better to interventions aimed at reducing their consumption, the AUDIT is preferable in clinical practice.

High lipid parenteral feeds raise plasma branched chain amino acid concentrations--a possible therapeutic approach to portasystemic encephalopathy?

The effect of varying the calorie source of parenteral feeding from an all glucose source to a high fat source has been studied in seven patients with normal liver function by randomised crossover trial. 'Intralipid' used as the major non-nitrogen calorie source (except for 400 kcal as glucose) was associated with significantly lower plasma concentrations of insulin and glucose, significantly higher plasma concentrations of the three branched chain amino acids, and a significantly higher urinary excretion of sodium. If these effects of a high fat parenteral feed were repeatable in patients with liver failure and portasystemic encephalopathy they might be of therapeutic benefit.

Hepatic abscesses complicating injection sclerotherapy of haemorrhoids.

We report the case of a 50-year-old man who developed a febrile illness four days after injection sclerotherapy of his haemorrhoids. The patient increasingly became unwell and was eventually found to have multiple hepatic abscesses. He made a complete recovery with antibiotic therapy. The importance of educating both patients and doctors about this complication is emphasized.

Intestinal capillariasis acquired in Egypt.

A 34-year-old Egyptian man presented with a 4-month history of profound weight loss, diarrhoea and abdominal pain. Extensive investigations in Egypt had failed to provide a diagnosis but subsequent stool examinations revealed ova of Capillaria philippinensis. The patient made a slow but complete recovery after treatment with albendazole. The literature on intestinal capillariasis is reviewed.

Preventing alcohol related birth damage: a review.

Since 1974 numerous clinical studies have made it clear that heavy alcohol consumption during pregnancy (in excess of 80 g or 8 units daily) can result in a child being born with a specific combination of physical and mental disabilities known as the Fetal Alcohol Syndrome. More moderate levels of intake (as little as 10 g of 1 unit daily) are associated with other fetal problems known as Fetal Alcohol Effects. The most common of these is growth retardation. Reduction of alcohol consumption is beneficial to pregnancy outcome. However, despite this great clinical and research interest within the field there has been comparatively little attention paid to researching possible preventative strategies and appropriate policy development. This paper first describes the size of the problem posed by drinking in pregnancy in the U.S.A. and the U.K., detailing the contrasting policy response on either side of the Atlantic. It examines the difficulties of formulating appropriate advice and then assesses the available research reports on preventative measures. The strategies described include general publicity and counselling for pregnant women. In addition, attention has been paid to the problems of dissemination by emphasising professional education. One major shortcoming is that most of these studies appear to have been carried out with little reference to existing knowledge on health education and promotion, or educational work in the antenatal or alcohol fields. In addition, little attention appears to have been paid to the characteristics of the groups at whom intervention might be targeted or the underlying social or psychological factors which maintain drinking in these groups. The second part of this paper, therefore, attempts to suggest appropriate avenues for developing preventative strategies by presenting a wide-ranging review with special reference to British experience. Particular attention is given to the issues of form and content of appropriate messages, targeting of risk populations, the venue for intervention, and media and the actual mechanisms involved in implementing the programme. We conclude that women should be advised to limit their alcohol consumption to no more than one unit a day when they are either pregnant or planning a pregnancy. We recommend that pregnant women should be asked about their alcohol and given appropriate advice during routine antenatal clinic visits. We suggest that the form of advice should be designed with the characteristics of the risk population in mind.(ABSTRACT TRUNCATED AT 400 WORDS)

High lipid parenteral nutrition improves portasystemic encephalopathy.

We have conducted a randomized double crossover study over 4 days in six parenterally fed patients with portasystemic encephalopathy (PSE) in which the nonprotein energy source of otherwise identical feeds was alternately all glucose or predominantly fat. Concentrations of plasma branched chain amino acids (BCAA), plasma insulin, and blood glucose were measured after an initial fast and subsequently after each of the four 24-hr periods of isonitrogenous feeding. The grade of PSE was assessed clinically and by the number connection test, BCAA concentrations were significantly lower during the glucose infusion than during fasting or the lipid infusion. PSE was significantly less with the lipid than with the glucose infusion. Trials testing the effect of infused BCAA must take account of the opposing effect on BCAA concentrations of simultaneous glucose infusion. A high lipid feed may have advantages in the short-term treatment of PSE.

The effect of khat chewing on gallbladder motility in a group of volunteers.

An increase in the prevalence of gallstones has been reported from the Middle East and the Republic of Yemen. Changing dietary habits and obesity are thought to be responsible but other local factors may contribute such as chewing the leaves of the khat plant (Catha edulis Forsk.) which is a widespread social custom in Yemen. We have studied the effects of khat chewing on gallbladder motility in a group of 10 healthy volunteers. All subjects underwent ultrasound measurements of gallbladder volume after chewing khat leaves or lettuce, which was used as the control. Results were compared after chewing for up to 2h in the fasting state and in response to a fatty meal. There was no significant change in gallbladder volume after chewing khat compared with lettuce in the fasting state (P=0.7) or in gallbladder emptying after a fatty meal (P=0.4) and we conclude that khat chewing has no clinically significant effect on gallbladder motility.

Metabolic basis for high paracetamol dosage without hepatic injury: a case study.

1. Studies of paracetamol metabolism were performed in a 58-year-old female with rheumatoid arthritis who had consumed 15-20 g paracetamol daily for 5 years without developing liver damage and data were compared with results in seven normal volunteers. 2. After a test dose of 2 g paracetamol, the formation of paracetamol sulphate and glucuronide conjugates detected in plasma from the patient was delayed by around 2 h relative to values in normal volunteers and the proportion of sulphate conjugates excreted in urine was 1.5 to 2 times those in normal volunteers (52% vs 26-35% of dose, respectively). The fractional metabolite clearance of paracetamol to glutathione-derived conjugates (0.28 ml min-1 kg-1) in our patient was > 30% lower than in normal females. 3. A combination of slow paracetamol absorption, enhanced detoxication of paracetamol (by sulphation) and reduced metabolism to potentially cytotoxic metabolites may have reduced the risk of liver damage in this patient. The latter may have reflected pharmacogenetic deficiencies in cytochrome P450 isoenzymes persisting despite chronic alcohol consumption (40-60 g per day) or resulted from inhibition of paracetamol activation by concomitant ingestion of aminophylline.

An evaluation of Dacron prostheses in the relief of jaundice due to malignant obstruction.

In 26 patients, relief of obstructive jaundice due to malignancy has been effected by inserting a Dacron biliary-enteric prosthesis. All cases were considered unsuitable for conventional biliary bypass procedures. The hospital mortality was 27% and mean survival of those patients discharged was 8 months. Insertion of a Dacron prosthesis may prove an alternative to percutaneous biliary stenting in selected patients with neoplastic biliary obstruction.

Trial of (+)-cyanidanol-3 in patients with hepatitis B chronic liver disease.

A double-blind controlled trial of 12 months' treatment with (+)-cyanidanol-3 was carried out in 26 patients with chronic hepatitis B liver disease. Treatment did not improve liver blood tests nor histological appearances of the liver, but there was a trend towards reduction of serum titres of hepatitis B surface antigen.

Randomised controlled trial of interferon alfa (lymphoblastoid interferon) in chronic non-A non-B hepatitis.

OBJECTIVE: To determine the effect of low dose interferon alfa (human lymphoblastoid interferon) on aminotransferase activities in chronic non-A non-B hepatitis. DESIGN: Prospective randomised controlled parallel group study of active treatment versus no treatment carried out over 16 weeks and preceded by baseline measurements at weeks 8 and 4 and time zero. SETTING: HEPATOLOGY outpatient clinics in secondary referral centres. PATIENTS: Fourteen adults with histologically proved chronic hepatitis and persistently raised aminotransferase activities for six months or more. INTERVENTIONS: Seven patients randomised to receive interferon alfa 5 megaunits (MU) daily for one week, reducing to 5 MU thrice weekly for seven weeks, then 3 MU thrice weekly for eight weeks. Controls not treated. END POINT: Control of hepatic enzyme activity in chronic non-A non-B hepatitis. MEASUREMENTS AND MAIN RESULTS: Serum aspartate aminotransferase activity remained raised in controls (mean increase in study period 23.4 U/l) but fell rapidly to normal in the treated group (mean decrease 106.4 U/l). In four cases values were normal by eight weeks and in five cases by 16 weeks. Only minor side effects were recorded (fever, myalgia), which became less common as treatment progressed. CONCLUSIONS: Continuous low dose interferon alfa reduces aspartate aminotransferase activity to normal in most patients with chronic non-A non-B hepatitis and may prevent progression to cirrhosis.

The effect of Qat chewing on blood pressure and heart rate in healthy volunteers.

The leaves of the Qat plant (Catha edulis Forsk., Celastraceae) which contain amphetamine like compounds are widely chewed in Yemen and East Africa for their pleasurable stimulant properties. There are also a number of unwanted side-effects and this paper studies the effect on heart rate and blood pressure in 80 healthy volunteers. During a 3-h period of chewing fresh Qat leaves there was a significant and progressive rise in systolic and diastolic blood pressure and heart rate, and levels had not returned to baseline 1 h after chewing had ceased. Further studies are needed on possible cardiovascular morbidity associated with regular Qat chewing.

Chewing Qat leaves slows the whole gut transit time.

Full text is available as a scanned copy of the original print version.