Symptomatic rebound methaemoglobinaemia after treatment with dapsone.

A 28-year-old female patient was admitted to our hospital with severe dyspnoea and hypoxemia due to methaemoglobinaemia caused by dapsone. The patient recovered completely after repeated infusions of methylene blue and cessation of dapsone. However, 12 days after cessation of dapsone, the patient was readmitted due to recurrence of symptoms based on a relapse of methaemoglobinaemia. Toxicological analysis revealed a toxic dapsone level at readmission and no other explanation for methaemoglobinaemia. Several possible mechanisms as explanation for the recurrence of methaemoglobinaemia are listed and additional tests were performed. In addition to supportive care, treatment consisted of methylene blue; furthermore, cimetidine and ascorbic acid were added. An overview of the pathophysiology, diagnostics, treatment, and possible explanations for this relapse of methaemoglobinaemia caused by dapsone are given. This case shows the importance of considering the possibility of a late rebound methaemoglobinaemia after discontinuation of dapsone.

Lack of evidence from HPLC 32P-post-labelling for tamoxifen-DNA adducts in the human endometrium.

Tamoxifen is associated with an increased incidence of endometrial cancer in women. It is also a potent carcinogen in rat liver and forms covalent DNA adducts in this tissue. A previous study exploring DNA adducts in human endometria, utilizing thin layer chromatography 32P-postlabelling, found no evidence for adducts in tamoxifen-treated women [Carmichael,P.L., Ugwumadu,A.H.N., Neven,P., Hewer,A.J., Poon,G.K. and Phillips,D.H. (1996) Cancer Res., 56, 1475-1479]. However, subsequent work utilizing HPLC 32P-post-labelling [Hemminki,K., Ranjaniemi,H., Lindahl,B. and Moberger,B. (1996) Cancer Res., 56, 4374-4377] suggested that very low levels could be detected. We have sought to investigate this question further by reproducing the HPLC methodology at two centres, and analysing endometrial DNA from 20 patients treated with 20 mg/day tamoxifen for between 22 and 65 months. Liver DNA isolated from tamoxifen-treated rats was used as a positive control. We found no convincing evidence for tamoxifen-derived DNA adducts in human endometrium. HPLC elution profiles of post-labelled DNA from tamoxifen-treated women were indistinguishable from those obtained with DNA from 14 untreated women and from six women taking toremifene, an analogue of tamoxifen.

Changes in receptor function by oxidative stress in guinea pig tracheal smooth muscle.

We studied the effects of hydrogen peroxide, hypochlorous acid and ozone on muscarinic and beta-adrenergic receptor responses in guinea pig tracheal tissue. Pretreatment of the tracheal strips with hydrogen peroxide (up to 10 mM) did not affect the muscarinic or beta-adrenergic receptor responses after stimulation with methacholine or (-)-isoprenaline respectively. In contrast to hydrogen peroxide, hypochlorous acid (1 mM and 10 mM) decreased the maximal contraction and the pD2-value after stimulation with the muscarinic agonist methacholine. Comparable effects were observed after stimulation with the beta-adrenoceptor agonist (-)-isoprenaline but the beta-adrenoceptor response seemed to be more susceptible to hypochlorous acid treatment than the muscarinic response. In other words, hypochlorous acid changes the balance between muscarinic and beta-adrenergic receptor responses of guinea pig tracheal strips in favour of the muscarinic receptor responses. In vivo exposure of the guinea pigs to 3 ppm ozone for two hours resulted in a hyperreactivity (increase in maximal contraction) after stimulation of the muscarinic receptor with methacholine. No effects were observed in the pD2-value. The beta-adrenergic receptor response was also affected after ozone exposure. No effects were seen in the maximal (-)-isoprenaline induced relaxation but there was an increase (hypersensitivity) in the pD2-value. Our data suggest that oxidative stress modulates receptor responses. Moreover, the type of oxidant seems to differentially affect various receptor responses. This may be of importance to further understand the influence of an oxidative effect (either directly via ozone or through inflammation) in lung tissue.

Characterization of rat plasma esterase ES-1A concerning its molecular and catalytic properties.

To characterize esterase ES-1A from rat plasma with regard to its molecular and catalytic properties, the enzyme was purified. The degree of purification, as measured by a densitometric gel scanning assay for ES-1 activity, was about 142-fold with a recovery of 9%. The ES-1A preparation was free of other plasma esterases but not of other plasma proteins. The enzyme shows microheterogeneity after staining for esterase activity in gradient polyacrylamide gel electrophoresis and isoelectric focusing. The native ES-1A protein is a carboxylesterase (EC 3.1.1.1) with a molecular mass of about 59 kDa as determined by gel filtration and gradient polyacrylamide gel electrophoresis. ES-1A exhibits a pI of 4.73 and optimum pH of 8.6 for p-nitrophenylbutyrate hydrolysis. With various p-nitrophenyl esters as substrate for ES-1A, it was found that the Michaelis constant decreased with increasing number of C atoms of the unbranched fatty acid moiety, whereas the maximum reaction velocity peaked with p-nitrophenylvalerate. The high degree of similarity of the properties of rat ES-1A with those reported earlier for mouse ES-2B, rabbit EST-2F, and human ESB2 suggests that these four esterases have a common evolutionary origin.

Anatomy of the orbicularis oris muscle in cleft lip.

The anatomy of the orbicularis oris muscle was studied using histological sections of 18 operative specimens of unilateral cleft lip (14 incomplete and 4 complete). In incomplete clefts the intrinsic part of the orbicularis, located in the vermilion, is simply interrupted without distortion. The extrinsic part, lying higher in the lip, crosses the cleft but is distorted vertically according to the degree of the nasal deformity. In complete clefts the intrinsic bundle ends in the submucosa of the vermilion as in incomplete clefts. The extrinsic bundle is deviated towards the ala nasi on the lateral side. On the medial side, the fibres are rarer and more horizontal. Conclusions are drawn regarding reorientation of the muscle fibres during cheiloplasty.

[Dermoid cyst of the tongue]. / Le kyste dermoïde de la langue.

An epidermoid cyst of the tongue with sinus tract is discussed. Its interest comes from the fact that histologic sections show sinus tract wall and epidermoïd cyst wall made with the same major characteristics of skin structures. Both have therefore the same embryologic origin. Adequate treatment is surgical excision.