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.

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.

CD10 immunostaining of bile canaliculi in liver biopsies: change of staining pattern with the development of cirrhosis.

AIMS: This study was prompted by published observations concerning the absence of normal bile canalicular CD10 staining in some cases of primary liver cell carcinoma. Our aim was to investigate the possibility that this loss of staining occurs prior to the development of cancer. METHODS AND RESULTS: The study comprised 164 liver biopsies, including 96 from patients with hepatitis C infection of various grades and stages including nine cases with cirrhosis, 24 other cases of cirrhosis of other aetiology, five cases of primary liver carcinoma, 12 cases of metastatic carcinoma, as well as biopsies with a variety of other liver diseases. CD10 was demonstrated in paraffin sections using the avidin-biotin immunoperoxidase technique. In hepatitis C cases, a significant loss of the canalicular pattern was seen in four out of 41 (10%) biopsies with stages 0-1 compared with 25 out of 55 (45%) with stages 2-6 (P < 0.001). There was also a significant difference (P < 0.001) between biopsies with stage 2-3 and those with stage 4-6, where marked pattern loss was seen in 9/37 (24%) and 16/18 (89%), respectively. Marked loss of the pattern was also seen in 16 out of the 24 (67%) other cirrhotic biopsies, as well as in cases with severe lobular inflammation and cholestasis and liver cell dysplasia and carcinoma. In hepatitis C biopsies, no relationship was noted between the reduction in the canalicular pattern and the necroinflammatory score. CONCLUSIONS: CD10-stained bile canalicular pattern in liver biopsies is preserved in cases with mild fibrosis and inflammation, but it becomes increasingly reduced with the advance of fibrosis or the presence of severe lobular inflammation or extensive metastases. Further investigations into the relationship between the changes in CD10 staining pattern and liver function tests may be useful in explaining test results.

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.

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.

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.

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.

A placebo-controlled phase I/II study of adefovir dipivoxil in patients with chronic hepatitis B virus infection.

Adefovir dipivoxil (bis-POM PMEA) is an adenine nucleotide analogue with activity against retroviruses and herpesviruses, and in vitro activity against hepatitis B virus (HBV). This study was conducted to evaluate its safety and antiviral activity in patients with chronic HBV infection. Twenty patients (13 co-infected with human immunodeficiency virus, HIV) were randomized in a phase I/II, double-blind, placebo-controlled study. Patients who had been hepatitis B surface antigen (HBsAg)/hepatitis B e antigen (HBeAg) positive for > or = 6 months, with elevated hepatic transaminases and serum HBV DNA > or = 50 pg ml-1, were randomized to adefovir dipivoxil 125 mg (n = 15) or placebo (n = 5) as a single, daily, oral dose for 28 days. Antiviral activity was assessed by changes in serum HBV DNA (using the Digene Hybrid Capture assay) and HBeAg/hepatitis B e antibody (HBeAb) status. HBV DNA levels fell rapidly by > 1 log10 in all active drug recipients (median fall 1.8 log10 pg ml-1) but increased by 0.01 log10 pg ml-1 in controls (P = 0.002). Reductions were sustained during treatment. HBV DNA returned to baseline over 1-6 weeks following discontinuation of active drug. HBeAg became transiently undetectable in one patient on treatment and, in another, sustained seroconversion to HBeAb occurred 12 weeks after treatment ended. Liver transaminase elevations > 300 U l-1 were observed in three patients during therapy (leading to protocol-specified treatment discontinuation or dose reduction) and in four patients during follow-up. On-treatment transaminase elevations were associated with HIV status, occurring in three of six HIV-uninfected patients compared with none of nine who were HIV infected. In addition, a slower return to baseline of serum HBV DNA levels was observed in the non-HIV-infected patients. Treatment for chronic hepatitis B as a once-daily oral dose was well tolerated and associated with significant and sustained reductions in serum HBV DNA levels during treatment. Transaminase elevations, which may be related to the therapeutic effect, were observed during and after treatment. Further studies are warranted to investigate the safety, and optimum dose and duration, of adefovir dipivoxil treatment for chronic hepatitis B.

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.

Chewing Qat leaves slows the whole gut transit time.

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Acute sporadic hepatitis in the Republic of Yemen.

The causes of acute icteric viral hepatitis were determined in 78 adult Yemeni patients. Acute hepatitis B (IgM anti-HBc positive) was the most common type (26.9%). Acute hepatitis E (IgM anti-HEV positive) occurred in 14% and was not associated with travel outside Yemen. Sixty percent of all 78 patients were positive for IgG anti-HEV as were 40% of a series of 48 healthy male blood donors and pregnant females, indicating that HEV is prevalent in Yemen. Acute hepatitis A (IgM anti-HAV positive) and hepatitis C and D were responsible for 5.1%, 6.4%, and 2.6% cases, respectively. This totals to 106%, as an infection with two viruses occurred in 6.4% cases. In 51.3% of all cases, no virological markers of acute hepatitis were detected, suggesting an as yet undiscovered agent.

Khat chewing and bladder neck dysfunction. A randomized controlled trial of alpha 1-adrenergic blockade.

OBJECTIVE: To assess whether the effect of chewing khat leaves (Catha edulis) on the urodynamics of healthy males is altered by the selective alpha 1-adrenergic blocking agent indoramin in a prospective randomized double-blind controlled trial. SUBJECTS AND METHODS: The urodynamics of 11 healthy males were studied before and during a khat chewing session preceded by indoramin or placebo. RESULTS: Khat chewing produced a fall in average and maximum urine flow rate. This effect was inhibited by indoramin. CONCLUSIONS: The urinary side-effects of khat chewing are probably mediated through stimulation of alpha 1-adrenergic receptors.

Indications, methods, and outcomes of percutaneous liver biopsy in England and Wales: an audit by the British Society of Gastroenterology and the Royal College of Physicians of London.

The liver section of the British Society of Gastroenterology and the research unit of the Royal College of Physicians collaborated to set up a nationwide audit to investigate the practice of percutaneous liver biopsy in England and Wales. Each of 189 health districts in England and Wales was approached to provide a list of 10 consecutive percutaneous biopsies performed during 1991, and details of demographic data, indications, suspected diagnosis, investigations, biopsy technique, outcome, and influence on patient management were collected. Data were retrieved on 1500 (79%). The age distribution showed 6% of biopsies were done in those over 80 years of age and as many over 90 as under 10 years of age. Suspected malignancy and chronic liver disease each contributed one third of the indications. In 34% the procedure was carried out by radiologists under ultrasound image control. The remainder were done by general physicians and gastroenterologists, with the operator in the second group being more senior and experienced. The Trucut biopsy needle accounted for two thirds of biopsies, the remainder being the Menghini type. For both needles the samples were recorded as excellent or satisfactory in 83% and inadequate in only 5%. Bleeding complicated 26 procedures (1.7%), requiring transfusion in 11, and was commoner when clotting was impaired or serum bilirubin raised. There were two definite and three possible procedure related, given an overall mortality of 0.13-0.33%. The diagnosis made before biopsy was confirmed in 63% of patients, and the clinician found the biopsy helpful in treatment in 75%. Day case biopsy and techniques to reduce the risk of bleeding were surprisingly rare in this series, which has given a unique opportunity to examine everyday practice across a wide range of hospitals.

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.

Post-hepatitis syndrome revisited.

To examine the role of acute hepatitis A and B infection in the aetiology of chronic fatigue syndrome and psychiatric morbidity we studied 40 patients with acute viral hepatitis A or B consecutively admitted to an infectious diseases unit and studied at least 6 months after recovery. Liver function tests (LFT) had returned to normal in each case. Forty-seven patients with other infectious diseases, of which 12 were presumed viral, admitted immediately after each hepatitis patient during the same period acted as controls. The main outcome measures were scores on a fatigue and muscle pain questionnaire, general health questionnaire (GHQ-12) and supplementary questions. The hepatitis cases scored significantly higher fatigue scores, GHQ-12 scores and muscle pain scores. Length of time since recovery from illness, age and sex were not confounding factors. Hepatitis cases were also less energetic, had greater weight change, had altered alcohol tolerance, had less exercise tolerance and felt less fit than the control group and compared with their premorbid state. Hence fatigue is more common after recovery in patients hospitalized for hepatitis A and B up to 30 months post-infection compared with matched controls hospitalized for other infectious diseases. Hepatitis A and B infection is a risk factor for post-infection fatigue, intermittent fatigue, as well as for psychiatric morbidity.

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.