Diffuse oesophageal leiomyomatosis (DL), an inherited smooth muscle proliferation process, has been reported to be associated with Alport syndrome (AS), a familial nephropathy, mainly dominant X-linked inherited, and characterized by ultrastructural changes of the glomerular basement membrane. The COL4A5 gene, encoding the alpha 5 chain of type IV collagen, has been identified as the site of mutations in families with X-linked AS. Recently, a novel alpha 6(IV) collagen chain encoding gene has been mapped closely upstream of COL4A5, and disruption of the 5' end of both genes has been reported in four patients with DL and AS (DL-AS). Here, we report a long-range restriction map around the COL4A6 locus, and show that the COL4A5/COL4A6 deletion observed in seven patients with DL-AS encompasses only the two first exons of COL4A6, with a breakpoint located in the second intron of COL4A6, whose size exceeds 65 kb. Furthermore, we demonstrate that three patients with AS without DL, known to have a deletion of the 5' part of the COL4A5 gene, display a larger deletion in COL4A6. Moreover, a COL4A6 mRNA product was detected by reverse-transcription-polymerase chain reaction in an oesophageal tumour sample of a patient with DL-AS. These results suggest that DL-AS could be caused by an abnormal truncated alpha 6(IV) chain.
Two hundred and nineteen children (boys: 56%, girls: 44%) were included in a randomized, double-blind, multicentre (4 centres) controlled trial designed to assess the efficacy and safety of ibuprofen (IBU) in the treatment of 1 to 6 year-old children with otoscopically proven acute otitis media (AOM), either unilateral or bilateral. They randomly received 10 mg/kg IBU (n = 71), or acetaminophen (PARA) (n = 73) or placebo (PLA) (n = 75), orally, tid, for 48 hours. All received oral cefaclor (Alfatil, Lilly, France) for seven days. They were evaluated before (D0) and at the end of treatment (D2). The main criterion of response was the aspect (landmarks and color) of the tympanic membrane assessed on a semi-quantitative scale from 0 to 6. Other criteria, assessed on semi-quantitative scales, included relief of pain (0 or 1), rectal temperature (0 to 2), and overall evaluation by parents of the improvement of quality of life on three items: appetite (0 to 2), sleep (0 to 2), and playing activity (0 to 2). The results at D2 were as follows: there was no significant difference between treatment groups as to the main criterion, but only a trend for IBU and PARA to do better than PLA but not for IBU to do better than PARA. From these data there is no argument to emphasize the utility of non-steroidal anti-inflammatory drugs (NSAIDs) in treating the inflammatory signs of the tympanic membrane in otitis. There was a statistically significant difference between treatment groups at D2 for pain, IBU being superior to PLA (P < 0.01): 7%, 10% and 25% of the children were still suffering at D2 in the IBU, PARA and PLA treatment groups, respectively. The difference between PARA and PLA for pain was not statistically significant. There was no significant difference between treatment groups for the other criteria. All treatments were well and equally tolerated. Although no significant difference was found between the treatment groups on the aspect of the tympanic membrane, the efficacy of IBU was evidenced on the relief of pain, the symptom that most disturbs the child.
IBD must be suspected in JIA patients treated with etanercept who develop intestinal symptoms, including anal abscess. This series raises the possibility of a relationship between etanercept therapy and the occurrence of IBD in a subset of patients with JIA.
If a tendency for a superior improvement with metoclopramide than with placebo was observed on the main end point, it was lower than expected and the difference was not significant. Compared with the corresponding single-stage design, the triangular test allowed to stop the study with a 15% reduction in sample size.
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