Relief of tracheal compression by aortopexy

We have performed aortopexy in 12 children with tracheal compression. Six infants had compression secondary to a vascular anomaly (group 1), and the other 6 had previous repair of esophageal atresia (group 2). Eleven of the 12 children are alive after a mean follow-up of 36 months. In group 1, 1 patient died and 3 patients (50%) experienced recurrent respiratory distress. Five infants sustained a major postoperative complication, and the average postoperative hospital stay was 25 days. In group 2, however, aortopexy was uniformly successful. There were no deaths, no postoperative complications, and no cases of postoperative respiratory distress, and the mean postoperative hospital stay was only 10 days. For children with reflex apnea after repair of esophageal atresia, aortopexy is lifesaving and can be performed with minimal morbidity and mortality. Great caution is indicated in children with tracheal compression from other causes.     

Corticotropin-releasing factor mRNA in rat thymus and spleen.

Corticotropin-releasing factor (CRF) initiates stress-induced immunosuppression via the hypothalamic-pituitary-adrenal axis. CRF has also been shown to have direct stimulatory and suppressive effects on immune cells. We have previously detected immunoreactive and bioactive CRF in the rat spleen and thymus. To determine if CRF is synthesized in these tissues, we analyzed rat spleen and thymus for the presence of CRF mRNA. RNA was reverse transcribed, and the resulting cDNA was amplified by the polymerase chain reaction with CRF gene-specific oligonucleotide primers. After Southern blotting and hybridization with an internal CRF gene probe, a product of the expected size was detected in the spleen, thymus, and hypothalamus (positive control) but not in liver or kidney (negative controls), indicating that CRF is synthesized in the spleen and thymus. Furthermore, CRF could be secreted from splenic and thymic adherent cells in culture. Secretion increased severalfold in response to nordihydroguaiaretic acid (NDGA), a lipoxygenase pathway inhibitor, whereas interleukin 1 had no effect, suggesting that regulation of CRF secretion may differ from that in the hypothalamus. CRF mRNA was detected in NDGA-stimulated thymic adherent cells and in both control and NDGA-stimulated splenic nonadherent cells. The finding that CRF is synthesized in the spleen and thymus suggests that locally synthesized "immune" CRF, acting as an autocrine or paracrine cytokine, may have direct regulatory effects on immune function.     

Stabilization of prolactin receptor in breast cancer cells

The role of the hormone prolactin (PRL) in the pathogenesis of breast cancer is mediated by its cognate receptor (PRLr). Ubiquitin-dependent degradation of the PRLr that negatively regulates PRL signaling is triggered by PRL-mediated phosphorylation of PRLr on Ser349 followed by the recruitment of the beta-transducin repeats-containing protein (beta-TrCP) ubiquitin-protein isopeptide ligase. We report here for the first time that interaction between PRLr and beta-TrCP is less efficient in human breast cancer cells than in non-tumorigenic human mammary epithelial cells. Furthermore, we demonstrate that both PRLr degradation and PRLr phosphorylation on Ser349 are impaired in breast tumor cells and tissues, an observation that directly correlates with enhanced expression of the PRLr in malignant breast epithelium. These findings represent a novel mechanism through which altered PRLr stability may directly influence the pathogenesis of breast cancer.     

Flow cytometric analysis of DNA content in Hürthle cell adenomas and carcinomas of the thyroid

Paraffin-embedded surgical biopsy material from 17 Hürthle cell tumors of the thyroid was examined for DNA content by flow cytometry to assess the diagnostic and prognostic utility of ploidy determinations in these rare tumors. Both adenomas (11 cases) and carcinomas (6 cases) were studied. As a control for methods, ten randomly selected normal autopsy thyroids were analyzed, all of which demonstrated normal diploid DNA content. Among the Hürthle cell tumors, however, aneuploid peaks were present in six adenomas (55%) and in four carcinomas (67%). Similarly, polyploid DNA peaks in the absence of other aneuploid peaks were present in two adenomas and two carcinomas (18% and 33%, respectively). These findings demonstrate the limited value of aneuploidy or polyploidy as diagnostic features for malignancy in Hürthle cell tumors of the thyroid. As for prognosis, there does not appear to be any unfavorable prognostic significance for abnormal DNA content in histologically benign Hürthle cell tumors treated by surgical excision because no metastases or recurrences occurred in this group at a mean disease-free follow-up of 50 +/- 19 months for six aneuploid lesions and 19 +/- 7 months for two polyploid adenomas. Preliminary data suggest that aneuploidy may, however, have an important prognostic value for histologically defined Hürthle cell carcinomas, because the only patient to die from the tumor in this series had an aneuploid Hürthle carcinoma. Thus, the authors' data indicate that the diagnostic utility of DNA content in Hürthle cell tumors is extremely limited and that there does not appear to be any negative prognostic significance for aneuploidy in histologically defined Hürthle cell adenomas.     

The in vitro development of extended-release solid oral dosage forms

A system is described for developing extended-release products, based upon predicting or simulating the entire plasma level-time curve to be expected from the administration of a controlled-release oral dosage form. Termed "biorelevant dissolution," it employs the product's in vitro dissolution behavior and the drug's pharmacokinetic parameters in conjunction with a classical pharmacokinetic model. The basic system is described along with some pertinent examples.     

Carney Complex: case report and review

Carney complex is a very rare multiple neoplasia syndrome with cardiac, cutaneous, and neural tumours with a variety of pigmented lesion of skin. We are reporting a rare case of carney complex in which left atrial myxoma with superficial angiomyxoma, giant cell tumour of bone and lentigines showed a unique association. This patient underwent successful surgical excision of left atrial myxoma under cardiopulmonary bypass.     

The influence of obstetric intervention on trends in twin stillbirths: United States, 1989–99

Objective: Although twin stillbirth rates have declined substantially over the past two decades, the contribution of changes in obstetric interventions to reducing twin stillbirths has not been quantified.

Methods: We carried out a retrospective cohort study of twin live births and stillbirths in the United States between 1989 and 1999 (n?=?1?102?212). Changes in the rate of stillbirth (???22 weeks) before and after adjustment for changes in labor induction, Cesarean delivery and sociodemographic factors were estimated through ecological logistic regression analysis. This analysis was based on aggregating data by each state within the United States.

Results: Between 1989 and 1999, rates of labor induction and Cesarean delivery among twin live births increased by 138% (from 5.8% to 13.8%) and 15% (from 48.3% to 55.6%), respectively. These changes were accompanied by a 43% decline in the stillbirth rate between 1989 and 1999 (from 24.4 to 13.9 per 1000 fetuses at risk). After excluding births weighing <?500?g, rates of labor induction among twins at 22–27 weeks', 28–33 weeks' and ??34 weeks' gestation increased by 95%, 131% and 127%, respectively, between 1989 and 1999. Cesarean delivery rates also increased by 55%, 29% and 2% in these same gestational age categories. The 48% (relative risk (RR) 0.52, 95% confidence interval (CI) 0.49–0.55) decline in stillbirth rate between 1989–91 and 1997–99 was reduced to a 25% (RR 0.75, 95% CI 0.72–0.79) decline after adjustment for changes in labor induction and Cesarean delivery. The decline in the rate of twin stillbirths was larger at later gestational ages (at ??32 and ??34 weeks) where the largest absolute increases in labor induction rates were observed.

Conclusions: The use of Cesarean delivery and especially labor induction for twin pregnancies has increased substantially in the United States over the last decade and these changes have been associated with a large decline in the rate of stillbirth among twins.