Anti-idiotypic antibodies specific for HLA in heart and kidney allograft recipients

Chronic rejection is the major threat to both heart and renal allograft survival. We have explored the possibility that some patients with anti-donor HLA antibodies (Ab1) develop specific anti-idiotypic antibodies (Ab2) which suppress the production of Ab1, and subsequently, the progression of chronic rejection. analysis of Ab2 in sera obtained from Ab1 producers showed that 22% of heart and 18% of kidney recipients produced Ab2. The 4- and 5-year actuarial graft survivals in Ab2 producers were 100% and 83%, respectively, compared to 57% in patients who formed Ab1 but not Ab2 (p<0.004). Patients carrying the DR2 alleles, DRB1*1501,*1502 or*1601 were at a lower risk of producing anti-donor HLA antibodies.     

Skinfold thickness versus isotope dilution for body fat assessment during simulated microgravity: results from three bed-rest campaigns in men and women with and without countermeasures

Because body composition is altered during head-down bed rest (HDBR), body mass can not be used as an index of energy balance. Consequently diet allowances should not be based on body mass evolution but on fat mass changes. Though criticized, skinfold thickness (ST) is the costless, easiest and fastest method to use for such an objective. The aim of this study was to compare the percentage of body fat (%BF) estimated by ST with the isotope dilution of H₂¹⁸O. We compiled data from three HDBR campaigns, one on women (n=8) in November 1998 and two on the same men (n=8) in December 1997 (without countermeasure) and January 1998 (with thigh-cuffs countermeasure), according to a crossover design. Body composition was assessed before and after 6 days of HDBR. %BF was derived from the biceps, triceps, sub-scapular and sup-iliac ST according to Durnin and Wormersly (1974). Fat-free mass was measured on the same day by H₂¹⁸O dilution and fat mass was calculated by the difference with body mass and expressed as a percentage. Based on precision tests, the minimum measurable change by ST was 1.1%BF for single measurement point. Both intercepts (F _4,30=0.89, P=0.45) and slopes (F _4,30=0.74; P=0.57) of the ST versus dilution relationships were not affected by the periods (December vs January), experimental conditions (control vs HDBR vs HDBR + thigh cuffs) or sex allowing the derivation of a common relationship %BF_st=0.94 × %BF_dil (F _1,47=97.9, P<0.0001; non-significant intercept excluded) with a bias between methods of −1.7±2.0 %BF (95% CI: −5.8, 2.4 %BF). ST can be used to measure %BF during HDBR provided great care is placed on training and changes are higher than 1.1 %BF. If the method can be applied for in-flight energy balance monitoring given the high observed energy deficit, a tight monitoring of the individual nutritional status as needed during simulation appears, however, dubious based on this solely method.     

Rectal thiopental for sedation of children for computed tomography.

Rectally administered thiopental was evaluated for sedation in pediatric computed tomography and compared with "cardiac cocktail" sedation. The drug produced sedation as effective as the "cocktail" with easier administration, more rapid onset, and shorter duration of sedation. Although no complications were observed, careful observation for respiratory depression is suggested.     

Specificity and regioselectivity of the conjugation of estradiol, estrone, and their catecholestrogen and methoxyestrogen metabolites by human uridine diphospho-glucuronosyltransferases expressed in endometrium

Uridine diphospho-glucuronosyltransferases (UGTs) inactivate and facilitate the excretion of estrogens to glucuronides (-G), the most abundant circulating estrogen conjugates. The identity of the conjugated estrogens formed by all known overexpressed UGTs (n = 16) was analyzed by comparison with retention time and mass fragmentation of authentic standards by HPLC tandem mass spectrometry methods. Six UGTs, namely 1A1, 1A3, 1A8, 1A9, 1A10, and 2B7, were found to glucuronidate estradiol (E(2)) and estrone (E(1)), their hydroxyls (OH), and their methoxy derivatives (MeO). Addition of glucuronic acid was catalyzed by specific UGTs at positions 2, 3, and 4 of the estrogens, whereas only E(2) was conjugated at position 17 by UGT2B7. Kinetic parameters indicate that the conjugation of E(2) at position 3 was predominantly catalyzed by 1A1, 1A3, and 1A8 and by 1A8 for E(1). Conjugation of 2-OHE(1)/E(2) and 2- and 4-MeOE(1)/E(2) was selective at position 3, mostly catalyzed by 1A1 and 1A8. Of all UGTs, UGT2B7 demonstrated the highest catalytic activities for estrogens and at least 10- to 50-fold higher activity for the conjugation of genotoxic 4-hydroxycatecholestrogens at position 4, compared with the conjugation of E(2), E(1), and 2-hydroxycatecholestrogens. Its presence was further shown in the endometrium by RT-PCR and immunohistochemistry, localizing in the same cells expressing CYP1B1, involved locally in the formation of 4-hydroxycatecholestrogens. Data show that several UGT enzymes detected in the endometrium are involved in the glucuronidation of E(2) and its 2-OH, 4-OH, and 2-MeO metabolites that exert various biological effects in the tissue.     

Allergic and nonallergic reactions to nitroglycerin.

Allergic and nonallergic reactions to nitroglycerin occur. The aims of this study were to review the different manifestations of nitroglycerin allergy, to explain how to evaluate for it, and to discuss its treatment. We reviewed relevant literature in peer-reviewed journals, computerized databases, and references identified from relevant bibliographics. Nitroglycerin's most common side effects are headache, facial flushing, head throbbing, fainting, hypotension, tachycardia, and syncope. The majority of reported skin reactions to topical and transdermal nitroglycerin products are irritant contact dermatitis, allergic contact dermatitis, and urticaria. Five cases of presumed allergic reactions to oral, sublingual, intravenous, or perianal nitroglycerin products have been described. Patch testing may be helpful in subjects with skin reactions to topical or transdermal nitroglycerin. In subjects with positive patch tests to nitroglycerin (allergic contact dermatitis), transdermal nitroglycerin patches and other topical nitroglycerin products should be avoided. Most patients with contact dermatitis to nitroglycerin have tolerated oral nitroglycerin, sublingual nitroglycerin, or oral isosorbide challenges.     

Seasonal variations of systemic lupus erythematosus flares in southern France

ObjectiveExposure to sunlight is one of the environmental factors involved in the pathogenesis of systemic lupus erythematosus. We investigated whether there is seasonal variation in the incidence of cutaneous and noncutaneous severe lupus flares in southern France.MethodsWe retrospectively reviewed clinical and biological data from all SLE patients hospitalized for a flare of the disease during a two year period in our centre and collected corresponding meteorological data from the official website of MeteoFrance.ResultsForty one patients, mean age 36.7 ± 13.8 years, were included. Twenty-six patients (63.4%) had kidney biopsy performed, showing in all cases proliferative nephritis, associated with membranous nephritis in 9 (22%). We found a clear seasonal pattern for overall lupus flares with 39% of flares occurred in Spring. Among patients without any cutaneous involvement, this seasonal pattern was still observed (p = 0.024). Patients under antimalarials presented flares significantly later in the sunny season than those without (respectively median in July versus May, p = 0.044). There were strong positive correlations between occurrence of lupus flares and maximum temperature increase (ρ = 0.87, p < 0.001), minimum temperature increase (ρ = 0.87, p < 0.001), and duration of sunshine increase (ρ = 0.78, p = 0.003). These correlations were also observed in patients with renal flares.ConclusionWe confirmed a seasonal pattern for lupus flares among patients living in Southern France, with most flares in spring, in correlation with an increase in temperature and duration of sunshine. A similar seasonal pattern was observed in patients with no cutaneous involvement and with visceral involvement.