Meningitis and midline facial deformity

A baby with unilateral cleft lip, midline cleft palate and hypertelorism developed meningitis in the first 48 h of life. Examination of the nasopharynx showed a soft tissue mass, which was confirmed as a basal encephalocele by computed tomography. There was also congenital hydrocephalus and the corpus callosum was absent. Surgical treatment included repair of the anterior basal skull defect, repair of the lip and palate, and ventriculo-peritoneal shunt. There is currently evidence of developmental delay and right-sided visual impairment due to Morning Glory syndrome. This case demonstrates that basal encephalocele should be considered in any baby with midline facial deformity who develops meningitis.     

Hyperbilirubinemia, hypocarbia and periventricular leukomalacia in preterm infants: relationship to cerebral palsy

This study comprised 103 preterm infants with a gestational age less than 33 weeks who were born in Tampere University Hospital and who were followed up to two years of age. Sixty-four perinatal variables were compared to ultrasound findings in the neonatal period and neurologic handicap at the age of two years. Duration of hypocarbia (PCO2 < or = 30 mmHg) during the first 72 h and hyperbilirubinemia (the mean level of serum total bilirubin) at three days of age were independently and significantly related to periventricular leukomalacia, but not directly to cerebral palsy. The only perinatal variables related independently and significantly to cerebral palsy at two years of age were periventricular leukomalacia and ventriculomegaly. According to these results, periventricular leukomalacia was the main predictor of cerebral palsy in preterm infants. In addition to hypocarbia, hyperbilirubinemia may also be involved in the pathogenesis of extensive (severe cystic) periventricular leukomalacia.     

Otoacoustic emissions as a screening test for hearing impairment in children

Transient evoked otoacoustic emissions (TEOAEs) are low amplitude sound waves produced by the healthy cochlea. They can be recorded with a microphone in the external ear. TEOAEs are abolished by hearing losses of 30 dB or more. The feasibility of using TEOAEs as a screening test for hearing loss in children was studied. TEOAE recordings were attempted in 56 children attending an audiology clinic. Recordings were possible from both ears in 52 children; of these 104 ears, 32 had hearing deficits of 30 dB or more. Hearing status was compared with the results of six TEOAE screening criteria. All criteria had a sensitivity of 1.00. Four standard TEOAE criteria yielded specificities of 0.46-0.58. Two new criteria derived from analysis of limited frequencies from the TEOAE waveform gave specificities of 0.76 and 0.82. It can be concluded that, when appropriate pass/fail criteria are employed, TEOAEs are a feasible screening test in children.     

The Fremantle Lead Study

Objective: To ascertain blood lead levels in a sample of preschool children from Fremantle, Western Australia, and to correlate these with possible risk factors.
Methodology The study was a cross-sectional prevalence survey of 120 children from day-care centres and 44 hospital inpatients. Blood lead and ferritin levels were determined and a risk factor questionnaire was completed by parents.
Results Of the 164 children 25.6% had lead levels above the NH&MRC goal (<10μg/dL). Nine of 133 (6.7%) had ferritin levels below 10 μg/L suggesting iron deficiency. Excessive blood lead concentrations as defined by the NH&MRC (>9μg/dL) related to: child's presence during house renovation (OR 3.35, P = 0.007, 95% Cl 1.39-8.81); Aboriginality (OR 6.4, P = 0.008, 95% Cl 1.6-24.9), and, in the 9-24 month age group, inversely to distance between home and a road carrying >7000 vehicles/day (r-0.56, P = 0.009, n = 24).
Conclusions A group of Fremantle children with unacceptably high blood lead levels has been identified. Renovation of older housing and Aboriginality are important risk factors.     

Prolapsed fallopian tube masquerading as adenocarcinoma of the vagina in a postmenopausal woman

A postmenopausal patient with vaginal prolapse of the fallopian tube presented with an erroneous diagnosis of adenocarcinoma of the vaginal apex. Failure to consider fallopian tube prolapse in the differential diagnosis of vaginal adenocarcinoma led to an upper vaginectomy and subsequent complication of a ureterovaginal fistula. The differential diagnosis of adenocarcinoma of the vagina in the postmenopausal patient and the management of vaginal prolapse of the fallopian tube are discussed.     

Traumatic flap displacement after LASIK

CASE REPORT: We present a case of traumatic displacement of corneal flap in the superior temporal quadrant 13 days after LASIK. The flap was repositioned after gentle irrigation of BSS, cleaned the interface and then drying the flap to verify its stability. In the next day the flap was adhered, clear cornea,smooth and visual acuity without correction was 1.00. DISCUSSION: We should try immediately to reposition the flap after traumatic displacement, as in this case.     

Structural refinement of inhibitors of urea-based soluble epoxide hydrolases

The soluble epoxide hydrolase (sEH) is involved in the metabolism of arachidonic, linoleic, and other fatty acid epoxides, endogenous chemical mediators that play an important role in blood pressure regulation and inflammation. 1,3-Disubstituted ureas, carbamates, and amides are new potent and stable inhibitors of sEH. However, the poor solubility of the lead compounds limits their use. Inhibitor structure-activity relationships were investigated to better define the structural requirements for inhibition and to identify points in the molecular topography that could accept polar groups without diminishing inhibition potency. Results indicate that lipophilicity is an important factor controlling inhibitor potency. Polar groups could be incorporated into one of the alkyl groups without loss of activity if they were placed at a sufficient distance from the urea function. The resulting compounds had a 2-fold higher water solubility. These findings will facilitate the rational design and optimization of sEH inhibitors with better physical properties.     

Use of ab initio calculations to predict the biological potency of carboxylesterase inhibitors

Carboxylesterases are important enzymes responsible for the hydrolysis and metabolism of numerous pharmaceuticals and xenobiotics. These enzymes are potently inhibited by trifluoromethyl ketone containing (TFK) inhibitors. We demonstrated that the ketone hydration state was affected by the surrounding chemical moieties and was related to inhibitor potency, with inhibitors that favored the gem-diol conformation exhibiting greater potency. Ab initio calculations were performed to determine the energy of hydration of the ketone, and the values were correlated with esterase inhibition data for a series of carboxylesterase inhibitors. This system was examined in three different mammalian models (human liver microsomes, murine liver microsomes, and commercial porcine liver esterase) and in an insect enzyme preparation (juvenile hormone esterase). In all cases, the extent of ketone hydration was strongly correlated with biological potency. Our results showed a very strong correlation with the extent of hydration, accounting for 94% of activity for human liver microsome esterase inhibition (p < 0.01). The atomic charge on the carbon atom of the carbonyl group in the TFK also strongly correlated with inhibitor potency, accounting for 94% of inhibition activity in human liver microsomes (p < 0.01). In addition, we provide crystallographic evidence of intramolecular hydrogen bonding in sulfur-containing inhibitors and relate these data to gem-diol formation. This study provides insight into the mechanism of carboxylesterase inhibition and raises the possibility that inhibitors that too strongly favor the gem-diol configuration have decreased potency due to low rate of ketone formation.