Longitudinal neurodevelopmental and neuromotor outcome in congenital diaphragmatic hernia patients in the first 3 years of life.

OBJECTIVE: The objective of this study was to longitudinally evaluate the neurodevelopmental (ND) outcome in congenital diaphragmatic hernia (CDH) survivors during the first 3 years of life. STUDY DESIGN: The study cohort consists of 47 CDH survivors that were enrolled in our prospective, follow-up program between July 2004 and September 2010, and underwent serial ND evaluations during the first 3 years of life. ND outcomes were evaluated using the Bayley Scales of Infant Development (BSID)-II or BSID-III. Persistent ND impairment was defined as a score that remained 79 for the cognitive, language and psychomotor domains at the most recent follow-up visit compared with the first assessment. RESULT: The median age at first and last evaluation was 8 (range, 5 to 15) and 29 (range, 23 to 36) months, respectively. During the follow-up, ND scores improved to average in 17%, remained average in 60%, remained delayed in 10%, improved from severely delayed to mildly delayed in 2% and deteriorated from average to delayed in 15%. Motor scores improved to average in 26%, remained average in 55%, remained delayed in 8% and improved from severely delayed to mildly delayed in 11%. Intrathoracic liver position (P=0.004), preterm delivery (P=0.03), supplemental O2 requirement at day of life 30 (P=0.007), age at discharge (P=0.03), periventricular leukomalacia (PVL; P=0.004) and initial neuromuscular hypotonicity (P=0.01) were associated with persistent motor delays. No relationship was found between patient's characteristics and the risk of persistent cognitive and language delays. CONCLUSION: (1) The majority of children with CDH are functioning in the average range by early preschool age, (2) most children who had early delays showed improvement in their ND outcome, (3) children showing delays in all the three domains were the least likely to show improvement and (4) CDH severity appears to be predictive of persistent psychomotor delays.

A critical role for NMDA receptors in parvalbumin interneurons for gamma rhythm induction and behavior.

Synchronous recruitment of fast-spiking (FS) parvalbumin (PV) interneurons generates gamma oscillations, rhythms that emerge during performance of cognitive tasks. Administration of N-methyl-D-aspartate (NMDA) receptor antagonists alters gamma rhythms, and can induce cognitive as well as psychosis-like symptoms in humans. The disruption of NMDA receptor (NMDAR) signaling specifically in FS PV interneurons is therefore hypothesized to give rise to neural network dysfunction that could underlie these symptoms. To address the connection between NMDAR activity, FS PV interneurons, gamma oscillations and behavior, we generated mice lacking NMDAR neurotransmission only in PV cells (PV-Cre/NR1f/f mice). Here, we show that mutant mice exhibit enhanced baseline cortical gamma rhythms, impaired gamma rhythm induction after optogenetic drive of PV interneurons and reduced sensitivity to the effects of NMDAR antagonists on gamma oscillations and stereotypies. Mutant mice show largely normal behaviors except for selective cognitive impairments, including deficits in habituation, working memory and associative learning. Our results provide evidence for the critical role of NMDAR in PV interneurons for expression of normal gamma rhythms and specific cognitive behaviors.

Blocking induction of T helper type 2 responses prevents development of disease in a model of childhood asthma.

Early-life respiratory viral infections are linked to subsequent development of allergic asthma in children. We assessed the underlying immunological mechanisms in a novel model of the induction phase of childhood asthma. BALB/c mice were infected neonatally with pneumonia virus of mice, then sensitized intranasally with ovalbumin following recovery. Animals were challenged with low levels of aerosolized ovalbumin for 4 weeks to induce changes of chronic asthma, then received a single moderate-level challenge to elicit mild acute allergic inflammation. To inhibit the initial induction of a T helper type 2 (Th2) response, we administered neutralizing antibodies against interleukin (IL)-4 or IL-25, then assessed development of airway inflammation and remodelling. Anti-IL-4 administered during chronic challenge prevented development of chronic and acute allergic inflammation, as well as goblet cell hyperplasia/metaplasia, but features of remodelling such as subepithelial fibrosis and epithelial hypertrophy were unaffected. In contrast, anti-IL-25 had limited effects on the airway inflammatory response but prevented key changes of remodelling, although it had no effect on goblet cells. Both antibodies suppressed development of a Th2 response, while anti-IL-25 also promoted a Th17 response. In further experiments, anti-IL-25 was administered in early life alone, and again had limited effects on airway inflammation, but prevented development of airway wall remodelling. We conclude that in this murine model of childhood asthma, administration of anti-IL-4 or anti-IL-25 prevents development of some key features of asthma, suggesting that suppression of development of a Th2 response during the neonatal period or later in childhood could be effective for primary prevention.

Microlaparoscopic technique for partial salpingectomy using bipolar electrocoagulation.

OBJECTIVE: To describe a technique of performing a partial salpingectomy using a small-diameter (2-mm) laparoscope and bipolar electrocoagulation. STUDY DESIGN: Sixty consecutive women desiring permanent sterilization underwent laparoscopic partial salpingectomy using a 2-mm transumbilical laparoscope and secondary midline sites suprapubically and midway above the pubis. A midportion of the tube was coagulated using Kleppinger forceps, transected with scissors and removed using grasping forceps. RESULTS: Additional time to remove both coagulated tubal segments averaged 4 minutes (range, 3-10). Each segment (mean, 1.5 cm; range, 0.9-2.4 cm) was confirmed in the operating room, then histologically. The transected tubal edges were separated with no thermal injury to nearby structures and with no mesosalpingeal hemorrhage. No cases required conversion from microlaparoscopy to a traditional method, and recovery time was not prolonged. The puncture sites healed well without sutures. CONCLUSION: Successful removal of electrocoagulated tubal segments with histologic confirmation was undertaken microlaparoscopically, with minimal additional operative time.

Vulvar leiomyoma associated with estrogen/progestin therapy. A case report.

Leiomyomata of the vulva are reported rarely. A previously unrecognized leiomyoma in the area of Bartholin's gland grew rapidly during estrogen/progestin replacement therapy. Hormone receptors for both estrogen and progesterone were positive.

Late sequelae of hysterectomy and diverticulosis: colovaginal fistulae.

Three cases of colovaginal fistulae were recently diagnosed and treated. Colovaginal fistulae are not commonly reported and their diagnosis may be difficult to make. Our cases presented with a complaint of vaginal discharge, history of hysterectomy, and diagnosis of diverticulosis. The diagnosis and treatment of colovaginal fistulae are discussed.

Pulmonary physiological and surfactant changes during injury and recovery from hyperoxia.

The time course of lung injury and recovery from a sublethal exposure to 100% O2 was investigated in adult rabbits. Animals were exposed to 100% O2 for 64 h and then returned to room air for varying periods of time up to 200 h. By the end of the exposure period, the alveolar permeability to solute increased significantly, and biochemical analyses of bronchoalveolar lavages showed a 30% decline in phospholipid content and a threefold increase in protein levels. However, other parameters such as wet-to-dry lung weight ratios, blood gas values, and pressure-volume mechanics were not significantly different from control levels after 64 h of hyperoxia. Twenty-four hours postexposure, alveolar phospholipid levels had declined even further (51% of control), and mean protein levels in lavage increased to eight times control values. These lavages exhibited severely impaired dynamic surface activity at 37 degrees C and 100% humidity in an oscillating bubble apparatus. In addition, total lung capacity, lung compliance, and arterial O2 partial pressure declined greatly at this time. Between 12 and 48 h postexposure, animal mortality was 35%; the remaining animals survived, and physiological parameters returned to normal by 200 h postexposure. Bronchoalveolar lavages from the recovered animals contained protein levels equal to those of controls and phospholipid levels approximately twice those in control lavages. Lavage surface activity also returned to normal by the 200 h postexposure time point.

Evaluation of the dating of gestation via the growth adjusted sonographic age method.

We compared the actual delivery dates of 248 normal pregnant women to the estimated dates of confinement (EDC) calculated from one biparietal diameter measurement (BPD) between 18 and 26 weeks of gestation and to the EDCs corrected by the growth adjusted sonographic age ( GASA ) method. The dating of gestation by those two ultrasound methods also was compared to the calculation of the gestational age from the last menstrual period in a subgroup of 61 women with highly reliable clinical data. The GASA method had no advantage over the dating of gestation using one single BPD measurement obtained before 26 weeks, nor over the dating of gestation using reliable menstrual data.