Review article: the association between nodular regenerative hyperplasia, inflammatory bowel disease and thiopurine therapy.

BACKGROUND: Nodular regenerative hyperplasia (NRH) is increasingly being recognised in patients with inflammatory bowel disease (IBD). However, the pathogenesis and incidence of NRH in IBD, and the putative roles played by azathioprine (AZA), mercaptopurine (MP), or tioguanine (TG) remain unclear. AIMS: To summarise the data on the association between NRH and thiopurine therapy in patients with IBD. METHODS: A literature search was performed in PubMed and MEDLINE databases using the keywords 'nodular regenerative hyperplasia AND (inflammatory bowel disease OR Crohn's disease OR ulcerative colitis) AND (azathioprine OR mercaptopurine OR tioguanine OR thioguanine).' No time limit was placed on studies included. RESULTS: Inflammatory bowel disease patients treated with AZA have a cumulative incidence of NRH of approximately 0.6% and 1.28% at 5 and 10 years, respectively, whereas those treated with high-dose TG (>40 mg/day) have a frequency of NRH of up to 62%, which is higher in patients with elevated liver enzymes and/or thrombocytopaenia than those without these abnormalities (frequency 76% vs. 33%). Conversely, low-dose TG therapy (<20 mg/day) is relatively safe, with no cases of NRH observed. NRH has also been found in 6% of operated thiopurine-naïve IBD patients. Male gender, older age, and stricturing disease/small bowel resection have been consistently identified as high-risk factors for NRH. CONCLUSIONS: The pathogenesis of nodular regenerative hyperplasia in patients with IBD is complex and multifactorial involving disease-specific, genetic and iatrogenic risk factors. Clinicians should maintain a high index of suspicion for diagnosing nodular regenerative hyperplasia, especially in IBD patients with high-risk factors on thiopurine therapy, regardless of the presence of laboratory abnormalities.

CYP2C19*17 gain-of-function polymorphism is associated with peptic ulcer disease.

Single-nucleotide polymorphisms (SNPs) in the CYP2C gene cluster have been extensively investigated as predisposing factors for nonsteroidal anti-inflammatory drug (NSAID)-induced peptic ulcer disease (PUD) or upper gastrointestinal bleeding (UGIB). However, results have been inconclusive owing to different study designs, limited genotyping strategies, and small sample sizes. We investigated whether eight functional SNPs in the CYP2C family of genes--CYP2C8*3 (rs11572080 and rs10509681), CYP2C8*4, CYP2C9*2, CYP2C9*3, CYP2C19*2, CYP2C19*3, and CYP2C19*17--are associated with PUD in 1,239 Caucasian patients. Logistic regression analysis showed that only CYP2C19*17 was associated with PUD (odds ratio additive model: 1.47 (95% confidence interval (CI) 1.12 to 1.92); P = 0.005; R(2) 16%), but not UGIB, independent of NSAID use or Helicobacter pylori infection. PUD distribution varied (P = 0.024) according to CYP2C19*17 genotype: *1/*1, 490 (64.3%); *1/*17, 304 (71.7%); and *17/*17, 31 (73.8%). CYP2C19*17, a gain-of-function polymorphism, is associated with PUD irrespective of etiology.

Comparison of axillary, rectal and tympanic temperature measurements in children admitted with malaria.

We compared axillary, rectal and tympanic temperatures in children admitted with severe malaria. The axillary temperatures were 0.74 degrees C (95% limits of agreement -0.85 to 2.33 degrees C) less than rectal temperatures and tympanic temperatures 0.42 degrees C (95% limits of agreement -0.16 to 2.44 degrees C) less than rectal temperatures. The difference was greater on admission than 24 hours later. These differences may be important in defining criteria for clinical syndromes.

Salicylate poisoning in children: report of three cases.

To raise clinicians' awareness of chronic (therapeutic) salicylate poisoning as a common cause of admission in paediatric patients presenting to hospital with respiratory distress (a clinical manifestation of metabolic acidosis) and a history of 'over the counter' treatment with salicylate (Aspirin). We present two complex cases and provide a review of the literature on pathogenesis, clinical presentation and management of salicylate poisoning. A complete history of the illness, including questions on drug use, is vital in assessing the cause of metabolic acidosis in children. Due to the limited options available in managing such patients in many developing countries, emphasis should be placed on prevention of poisoning by educating the community and health care providers.