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.      

Eccentric visual acuity in patients with macular disease

A series of cards each containing a two dimensional array of identical Snellen "E's" was used to determine best eccentric visual acuity in patients with macular disease having Snellen visual acuity of 20/70 or worse. Each "full field E" card simultaneously presents the same letter to foveal and parafoveal areas. This test can therefore determine quickly if potentially useful vision is present in any area of the central visual field. In our study of 37 eyes, 70% demonstrated potential visual acuity at least two times better than visual acuity measured by conventional methods, and 20% demonstrated at least a fourfold improvement. This suggests that most patients with macular disease do not spontaneously employ their best remaining area of retina for fixation.     

Original papers: A combination horizontal/vertical prism bar A precisely calibrated tool for use in front of one eye

The authors used an optical bench to investigate calibration and errors from improper positioning of prism bars manufactured by R.O. Gulden and Luneau. They urged Gulden to redesign its prism bars to be used back-to-back in front of one eye. The horizontal bar is held with its flat face posteriorly within a channel on the flat face of the vertical bar; the interface is positioned perpendicular to the direction of the fixation object, which demands that the horizontal prism bar be calibrated in the frontal plane position and the vertical bar in the Prentice position. Analysis of calibration demonstrated that Gulden's new combination horizontal/vertical prism bar can be used without significant error (within + 0.5δ of labelled values). Gulden's old vertical prism bar is also calibrated in the Prentice position. Luneau's horizontal and vertical prism bars are calibrated close to the frontal plane position (within +1.0δ and +0.4δ respectively). Improper positioning demonstrated an increasing error with larger prisms. Luneau's 25δ segment measured 27.8δ in the Prentice position, the 40δ segment 67.5δ. The 25δ segment of Gulden's new and old vertical prism bars measured 23.25δ in the frontal plane position. Gulden's vertical prism bars should always be held with the flat surface toward the examiner. Luneau's horizontal and vertical prism bars should be held one in front of each eye when used simultaneously; thus, neither eye is looking directly at the fixation object and defining primary and secondary deviations is not possible. The combination horizontal/vertical prism bar is manufactured by Gulden Ophthalmics, 225 Cadwalader Avenue, Elkins Park, PA 19117-2097. The Luneau prism bars are manufactured by Luneau Ophtalmologie, B.P. 252, 28005 Chartres Cedex, France. The authors have no proprietary or financial interest in these products or in the companies involved.     

The Lancaster red-green test before and after occlusion in the evaluation of incomitant strabismus.

BACKGROUND: Patients with incomitant strabismus can often fuse in a limited area of gaze. Prolongation of neurologically learned fusional vergence tone ("vergence adaptation") in and near this area can result in misleading measurements with standard clinical measures of strabismus. Monocular occlusion for at least 30 minutes eliminates most of the effect of vergence adaptation. The Lancaster red-green test provides an elegant and convenient map of incomitant strabismus. We investigated the efficacy of the Lancaster red-green test before and after monocular occlusion for the investigation of incomitant strabismus. METHODS: We retrospectively studied the results of the Lancaster red-green test in 6 patients with incomitant vertical strabismus in whom we suspected that vergence adaptation might be distorting the pattern of deviation. The test was performed before and after monocular occlusion for 30 to 60 minutes, and the preocclusion and postocclusion results were compared. RESULTS: In the 6 cases studied, the Lancaster red-green test showed at least a 5-PD increase in the hyperdeviation, after monocular occlusion. The increases were mostly in primary gaze and downgaze, which tended to regularize the pattern of deviation. CONCLUSIONS: The combination of monocular occlusion and the Lancaster red-green test is useful for uncovering the effect of vergence adaptation. Such results may often simplify the planning of surgical correction because the incomitance usually decreases after monocular occlusion, making it less likely that surgery will worsen the alignment in the area previously fused. We recommend that monocular occlusion should be considered when planning surgery or even prism correction for incomitant deviations, especially when the initial Lancaster red-green test shows an unexpected incomitant pattern where there is fusion in 1 direction of gaze but not in others.     

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.