Modelling purine derivative excretion in dairy goats: endogenous excretion and the relationship between duodenal input and urinary output.

To determine the endogenous contribution of purine derivatives (PD) to renal excretion and the urinary recovery of duodenal purine bases (PB), five dairy Granadina goats (initial weight ± s.e.: 38.6 ± 2.78 kg) were each fitted with a duodenal infusion catheter. Animals were offered ad libitum a mixed diet (75 : 25; alfalfa hay : concentrate), which was supplied in equal portions every 3 h. To label microbial PB, (15NH4)2SO4 was added to the concentrate. The lower enrichment of urinary PD (15N-allantoin) compared with duodenal PB enrichment confirmed the presence of an endogenous PD fraction (268.5 ± 21.98 µmol/kg weight0.75 or 0.386 of the total PD excretion). The recovery of PD in urine and milk increased linearly in response to increasing amounts of duodenally infused RNA (starting on day 21 after parturition). On average, 0.74 of infused PB from RNA was recovered in urine. Milk PD constituted a minor (<0.01) fraction of the total PD excretion and this fraction decreased as the amount of infused PB increased. Our findings indicate that lactation in goats did not affect the urinary recovery of duodenal PB but increased the endogenous contribution to urinary excretion of PD.

Ischemic colitis or melanosis coli: a case report.

BACKGROUND: Melanosis Coli is described as black or brown discolouration of the mucosa of the colon. Its a benign condition, which arises from anthraquinone laxative abuse and has no symptoms of its own. The main importance of diagnosing Melanosis Coli correctly lies in the fact that if its extensive, there may be difficulty in differentiating it from ischemic colitis. CASE PRESENTATION: We present a case of extensive Melanosis Coli involving the whole of large bowel that appeared gangrenous. A sub total colectomy was performed on presumed diagnosis of ischemic bowel. CONCLUSION: This report reminds the clinicians that extensive Melanosis Coli may mimic ischemic colitis and thus must be considered as a differential diagnosis.

Should domperidone be used for the treatment of gastro-oesophageal reflux in children? Systematic review of randomized controlled trials in children aged 1 month to 11 years old.

AIM: To determine whether there is robust evidence of efficacy for domperidone in reducing the symptoms of gastro-oesophageal reflux (GOR) and gastro-oesophageal reflux disease (GORD) in children. METHODS: Systematic review of randomized controlled trials (RCTs). A search was made of the Cochrane Library Issue 2004 (Central Register of Controlled Trials and Database of Systematic Reviews), Medline (Pub-med) 1966 to present and Embase from 1974 to 2004, and reference citations of the RCTs that had been found electronically. RESULTS: Four RCTs were identified. Only the two older trials showed any benefits of domperidone on clinical symptoms of GORD in older children, which were the primary outcome measures. In the trial undertaken by Clara, a good or excellent result was obtained in 93% of the domperidone group compared with 33% of the controls (P < 0.05). In the trial undertaken by de Loore, after 2 weeks of treatment 75% of patients treated with domperidone were found not to be vomiting, compared with 43% in the metoclopramide group and 7% in the placebo group. The trial by Corraccio gave no detailed results regarding the primary outcomes of effect of domperidone on symptoms but simply reported 'cured', 'improved' or 'unchanged'. The secondary pH-metric outcome of the number of reflux episodes, was reduced with domperidone. CONCLUSION: From the limited evidence available, there was no robust evidence of efficacy for the treatment of GOR with domperidone in young children. Given the usually benign nature of the condition, the widespread use of unlicensed medicines for GOR is not warranted.

Clinical pharmacology of ondansetron in postoperative nausea and vomiting.

Ondansetron is a 5-HT3 receptor antagonist which is effective and well tolerated as an antiemetic for emesis induced by cancer chemotherapy and radiation therapy, and in the prevention and treatment of postoperative nausea and vomiting. Ondansetron is rapidly absorbed after oral administration (tmax 1.9 h) with an absolute bioavailability of around 60%. Its terminal elimination half-life is 3.5 h and it is extensively hepatically metabolized. Plasma clearance is 0.38 litre h-1 kg-1 and volume of distribution is 1.8 litre kg-1. Plasma clearance is reduced by age (31% reduction) and hepatic failure (80% reduction in severe failure). In patients undergoing general anaesthesia there is a slight prolongation of terminal half-life, which is not of clinical significance. Ondansetron is very well tolerated in volunteer studies. Headache, mild abdominal pain, and constipation occur infrequently. There is no evidence for effects of ondansetron on cardiac function (electrocardiogram, cardiac output, blood pressure and heart rate), and haemostatic function in volunteers and patients. Respiratory depression induced during general anaesthesia is not potentiated by ondansetron. No drug interactions have been noted with temazepam, atracurium, alfentanil and alcohol in man. There are also no interactions seen in animal studies using pentobarbitone, morphine, neostigmine, prednisolone and diazepam.

The role of histamine in the acute inflammatory responses to intradermal platelet activating factor.

1. The role of histamine in PAF-induced acute inflammatory responses (flare and weal) in the skin has been evaluated in a series of three separate studies. 2. Terfenadine, a potent H1-selective histamine antagonist virtually abolished the flare response and significantly inhibited the weal response. 3. Histamine depletion in the skin using compound 48/80 resulted in similar effects on the flare and weal response. Two consecutive daily injections of compound 48/80 were found to deplete comprehensively skin sites of histamine and the ability of skin to respond to PAF was completely restored within 2 weeks of compound 48/80 treatment. 4. Intradermally injected PAF was associated with acute rises in plasma histamine in blood drawn from a draining vein with peak concentrations occurring within 5 min of injection. 5. No difference in PAF-induced flare and weal response was found between atopic and non-atopic subjects and this was reflected in the peak plasma histamine results. A significantly higher baseline plasma histamine was found in the atopic group, however, when compared with the non atopic group. 6. It is concluded that histamine has an important role in the acute inflammatory responses to intradermally injected PAF, although there does appear to be a significant direct vascular component in the PAF-induced weal response.

The clinical pharmacology, pharmacokinetics and metabolism of sumatriptan.

Clinical pharmacology studies were undertaken in young healthy volunteers, in a small number of elderly subjects and in migraine subjects during and between attacks. Absorption after subcutaneous and oral administration was rapid. Bioavailability was nearly 100% after subcutaneous administration and averaged 14% after oral administration. Elimination was predominantly by metabolism to a non-active indoleacetic acid analogue. The plasma half-lives of sumatriptan and the metabolite were about 2 h. Pharmacokinetic and pharmacodynamic variables were similar in all groups studied and were not altered by the presence of food, alcohol, dihydroergotamine or prophylactic migraine treatments. Sumatriptan produced a number of minor adverse events, but had no clinically significant effect on routine haematological or biochemical investigations using the intravenous, subcutaneous or oral routes. Transient rises in blood pressure were observed which were no greater than those that would be anticipated during moderate exercise. The physician-administered subcutaneous injection resulted in transient stinging at the site of injection in many subjects; administration using the auto-injector was better tolerated.