Mutational analysis of the SOX9 gene in campomelic dysplasia and autosomal sex reversal: lack of genotype/phenotype correlations

It has previously been shown that, in the heterozygous state, mutations in the SOX9 gene cause campomelic dysplasia (CD) and the often associated autosomal XY sex reversal. In 12 CD patients, 10 novel mutations and one recurrent mutation were characterized in one SOX9 allele each, and in one case, no mutation was found. Four missense mutations are all located within the high mobility group (HMG) domain. They either reduce or abolish the DNA-binding ability of the mutant SOX9 proteins. Among the five nonsense and three frameshift mutations identified, two leave the C-terminal transactivation (TA) domain encompassing residues 402-509 of SOX9 partly or almost completely intact. When tested in cell transfection experiments, the recurrent nonsense mutation Y440X, found in two patients who survived for four and more than 9 years, respectively, exhibits some residual transactivation ability. In contrast, a frameshift mutation extending the protein by 70 residues at codon 507, found in a patient who died shortly after birth, showed no transactivation. This is apparently due to instability of the mutant SOX9 protein as demonstrated by Western blotting. Amino acid substitutions and nonsense mutations are found in patients with and without XY sex reversal, indicating that sex reversal in CD is subject to variable penetrance. Finally, none of 18 female patients with XY gonadal dysgenesis (Swyer syndrome) showed an altered SOX9 banding pattern in SSCP assays, providing evidence that SOX9 mutations do not usually result in XY sex reversal without skeletal malformations.      

The influence of reported paternal attitudes on the decision to breast-feed

Objective: To identify factors that influence a woman's decision to breast-feed.
Methodology: Five hundred and fifty-six women were recruited from the maternity wards of two Perth hospitals. Data were collected from a self-administered questionnaire completed by participants prior to discharge. Logistic regression analysis was used to determine factors influencing the initiation of breast-feeding.
Results: At discharge from hospital 83.8% of women were breast-feeding, including 6% who were giving complementary formula feeds. After controlling for potentially confounding demographic and biomedical factors, the father's reported preference for breast-feeding was found to be the most important factor influencing a woman's decision to breast-feed (OR 10.18).
Conclusion: Fathers participate in and influence the choice of infant feeding method and should be included in breast-feeding discussions.     

Margin of safety for discharge after apnea in preterm infants

OBJECTIVE: Most neonatologists include an apnea-free period in the criteria for the discharge of preterm infants. However, the length of time one should wait after the cessation of apnea before sending an infant home without a monitor is debated. We undertook this study in an attempt to define a minimal and safe observation period between the time of the last apnea episode and discharge. METHODS: We reasoned that in infants with idiopathic apnea of prematurity, the intervals between days on which apnea occurs gradually increase until some point at which clinically significant apnea ceases. Therefore, knowledge about the intervals between days on which apnea occurred just before the last apnea would provide a reasonable estimate of the minimal safe observation interval between the last apnea and discharge. We reviewed the charts of 266 infants born in 1993 and 1994 at 相似文献   

Inhibition of cigarette smoke-related lipophilic DNA adducts in rat tissues by dietary oltipraz

The present study investigated the effects of dietary oltipraz on cigarette smoke-related lipophilic DNA adduct formation. Female Sprague- Dawley rats were exposed daily to sidestream cigarette smoke in a whole- body exposure chamber 6 h/day for 4 consecutive weeks. One group of rats was maintained on control diet while another group received the same diet supplemented with either a low (167 p.p.m.) or high (500 p.p.m.) dose of oltipraz, starting 1 week prior to initiation of smoke exposure until the end of the experiment. Analysis of lipophilic DNA adducts by the nuclease P1-mediated 32P-post-labeling showed up to five smoke-related adducts. Adduct no. 5 predominated in both the lung and the heart while adduct nos 3 and 2 predominated in the trachea and bladder, respectively. Quantitative analysis revealed that the total adduct level was the highest in lungs (270+/-68 adducts/10(10) nucleotides), followed by trachea (196+/-48 adducts/10(10) nucleotides), heart (141+/-22 adducts/10(10) nucleotides) and bladder (85+/-16 adducts/10(10) nucleotides). High dose oltipraz treatment reduced the adduct levels in lungs and bladder by >60%, while the reduction in lungs in the low-dose group was approximately 35%. In trachea, the effect of low and high dietary oltipraz on smoke DNA adduction was equivocal, while smoke-related DNA adducts in the heart were minimally inhibited by high-dose oltipraz. In a repeat experiment that employed a 3-fold lower dose of cigarette smoke, oltipraz (500 p.p.m.) was found to inhibit the formation of DNA adducts in rat lungs and trachea by 80 and 65%, respectively. These data clearly demonstrate a high efficacy of oltipraz in inhibiting the formation of cigarette smoke-induced DNA adducts in the target tissues.      

Genitalverstümmelung und Strafrecht

Some of the girls who live in Germany and have Muslim parents are threatened by female genital mutilation. This report describes the kinds and medical consequences of female genital mutilation as well as the criminal judgement. Female genital mutilation is considered as dangerous bodily harm, not as grievous bodily harm. Consent does not justify the infringement of rights. The argument that Islam justifies the infringement of rights is irrelevant by law. The human right of bodily intactness has priority over the right of religious freedom. Finally the legal regulations about dealing with personal data are presented. A legal compulsory registration still does not exist.     

Cyclosporine as prophylaxis for graft-versus-host disease: a randomized study in patients undergoing marrow transplantation for acute nonlymphoblastic leukemia

Seventy-five patients, 13 to 49 years of age, with acute nonlymphoblastic leukemia in first remission were treated with cyclophosphamide, fractionated total body irradiation, and marrow transplantation from an HLA-identical sibling and randomized to receive either cyclosporine (CSP) (n = 36) or methotrexate (MTX) (n = 39) as prophylaxis for graft-v-host disease (GVHD). All patients engrafted, and 22 who were given CSP and 21 who were given MTX, are alive at 20 to 47 (median, 35) months (P = .5). Engraftment as assessed by granulocyte recovery (P less than .0005) and platelet transfusion requirement (P = .01) was faster in patients on CSP. Twelve patients (33%) on CSP and 22 (56%) on MTX developed acute GVHD of grades II through IV (P = .07) and 15 of 30 on CSP and 14 of 32 on MTX that were at risk developed chronic GVHD. The most frequent causes of death were interstitial pneumonitis and marrow relapse of leukemia, which occurred with similar frequency in both groups. Beneficial effects observed in patients on CSP included less severe mucositis and shorter duration of hospitalization; adverse effects included renal function impairment and hypertension. These data confirm that CSP is a useful immunosuppressant in patients undergoing marrow transplantation but fail to show a significant improvement in survival as compared with the standard regimen of MTX.