Cell surface expression of epidermal growth factor receptor and Her-2 with nuclear expression of Her-4 in primary osteosarcoma

There is controversy over the role of Her-2 in osteosarcoma, with some investigators reporting association between expression and adverse outcome, whereas others point to the lack of gene amplification and membranous expression by immunohistochemistry (IHC) as inconsistent with biological significance. Her-2 normally requires pairing with epidermal growth factor receptor (EGFR), Her-3, or Her-4, but these have been less well studied in osteosarcoma. We evaluated the expression of each of these receptors in osteosarcoma and their potential to contribute to pathogenesis by examining a panel of low-passage primary osteosarcoma cell lines, comparing these with archival tumor specimens. Her-2 immunoreactivity was seen frequently in the diffuse staining pattern described previously. We observed EGFR in all samples by IHC. Her-3 expression was not observed. Her-4 expression was nuclear in distribution in all tumor samples and many cell line samples, consistent with activation and cleavage of the receptor. Quantified expression of Her-2 and EGFR mRNA by quantitative, real-time PCR in cell lines correlated with IHC for Her-2 but not for EGFR. Western blot identified full-length receptors for EGFR and Her-2 in all expected cell lines and showed Her-4 to be predominantly in the p80 form. Flow cytometry identified cell surface Her-2 and EGFR in all lines with receptor expression by IHC. We conclude that the cell surface expression of Her-2 and EGFR and the nuclear localization of the activated p80 fragment of Her-4 suggest that all three may be contributing to osteosarcoma pathogenesis. Therapy directed against this family of receptors may be beneficial for patients with osteosarcoma.     

Evolution of the human brain, chorionic gonadotropin and hemochorial implantation of the placenta: insights into origins of pregnancy failures, preeclampsia and choriocarcinoma

Hyperglycosylated chorionic gonadotropin (CG-H) signals placental cytotrophoblast cell growth and invasion, and chorionic gonadotropin (CG) promotes uterine vascularization. A hypothesis is presented relating the evolution of these molecules to the evolution of human hemochorial implantation and that of the human brain. Deep placental invasion, vascularization and hemochorial placentation, under the influence of CG and CG-H, are a critical part of the nutrition and energy-generating mechanisms needed for human brain development and thus for the evolution of humans. Insufficient CG-H production and the resulting inappropriate implantation is associated with an unduly high incidence of pregnancy failures in humans. Low levels of CG-H and inappropriate hemochorial placentation also appear to be associated with subsequent preeclampsia. It is also of note that human CG-H drives invasion by gestational trophoblastic neoplasms that have been described only in humans.     

Quercetin and rutin as potential sunscreen agents: determination of efficacy by an in vitro method

Given that flavonoids are known for their ultraviolet (UV)B photoprotective properties in plants that contain them, we chose to study quercetin (1) and rutin (2) as agents that could potentially be used in sunscreen products. These two substances proved to behave in similar ways. When incorporated in oil-in-water emulsions, at a concentration of 10% (w/w), 1 and 2 give sun protection factor (SPF) values similar to that of homosalate, a standard substance. These two flavonoids also provided a non-negligible level of photoprotection in the UVA range. When used in association with titanium dioxide, the SPF obtained was around 30.     

The identification, management, and prevention of conflict with faculty and fellows: A practical ethical guide for department chairs and division chiefs

The relationship between chairs and divisions chiefs with faculty colleagues in departments of obstetrics and gynecology has important but heretofore unexplored ethical dimensions. Based on the ethical concept of fiduciary responsibility and contractual obligations, this paper provides ethically justified practical guidance for academic physician leaders in the identification, management, and prevention of conflicts in their relationships with faculty colleagues. The framework is developed in contrast with the fiduciary-contractual dimensions of the physician-patient relationship and is articulated in terms of the ethical principles of beneficence, respect for autonomy, and justice. The distinctive nature of the academic physician leader-colleague relationship is that beneficence-based obligations and justice-based obligations to colleagues can often justifiably override autonomy-based obligations to colleagues, about which it is crucial for academic leaders to be transparent in making and implementing leadership decisions.     

Primitive neuroectodermal tumor of the myometrium with cardio-vascular symptoms

BACKGROUND: Non-bacterial thrombotic endocarditis is a severe complication of cancer, rarely reported in gynecologic tumors. However, it can be inaugural and lead to complex diagnostic pathways. CASE: A 40-year-old woman presented with a stroke, related to an endocarditis. The valvular vegetation was surgically removed, and a malignant node was resected. A PET-scan led to the diagnosis of a myometrial tumor, which was found to be a primitive neuroectodermal tumor (PNET). The patient underwent total abdominal hysterectomy with bilateral salpingo-oophorectomy, and systemic chemotherapy which allowed a complete remission of tumoral and cardio-vascular symptoms. CONCLUSION: To our knowledge, this is the first case report of a PNET of the myometrium revealed by cardio-vascular symptoms.     

Neonatal and 5-year outcomes after birth at 30-34 weeks of gestation

OBJECTIVE: To evaluate the rates of in-hospital death, neonatal complications, and 5-year outcomes of infants born at 30-34 weeks of gestation. METHODS: In nine regions of France, all 2,020 stillbirths and live births at 30, 31, and 32 weeks in 1997 and all 457 births at 33 and 34 weeks in April and October 1997 were recorded. Survivors were evaluated at 5 years of age. RESULTS: Increasing gestational age from 30 to 34 weeks was associated with progressive decreases in in-hospital mortality (from 8.1% to 0.4%) and neonatal complications (respiratory distress syndrome, 43.8% to 2.6%; maternofetal infections, 7.2% to 2.6%; and severe white matter injury, 5.5% to 1.3%). Although infants at 33 and 34 weeks of gestation rarely experienced necrotizing enterocolitis, bronchopulmonary dysplasia, or nosocomial infections, they still required endotracheal ventilation, antibiotics, or parenteral nutrition. At 5 years of age, older gestational age was associated with significant decreases in rates of cerebral palsy (6.3% at 30 weeks and 0.7% at 34 weeks) and mild to severe cognitive impairments (35.3% at 30 weeks and 23.9% at 34 weeks). In singletons, preterm rupture of membranes or preterm labor carried an increased risk of cerebral palsy but not of cognitive impairment. CONCLUSION: Neonates born at 30-34 weeks experienced substantial morbidity and often required admission to neonatal intensive care units. These outcomes suggest that prolonging pregnancies beyond 34 weeks may be desirable whenever possible. Infants born at 30-34 weeks should be carefully monitored to ensure prompt detection and management of neurodevelopmental impairment.     

Laparoscopic treatment of recurrent small bowel obstruction secondary to ileal endometriosis

Endometriosis is a relatively common condition characterized by implantation and proliferation of endometrial glands outside the uterus affecting 8% to 15% of women. Intestinal involvement is common, reported in 12% to 37% of individuals with the disease. The sites most often affected are the sigmoid colon and rectum (85%), while small bowel involvement is seen less frequently (7%) and usually confined to the distal ileum. The cecum (3.6%) and appendix (3%) are the sites least affected.