Persistent fetal circulation.

Persistent fetal circulation (PFC), also known as persistent pulmonary hypertension of the newborn, is defined as postnatal persistence of right-to-left ductal or atrial shunting, or both in the presence of elevated right ventricular pressure. It is a relatively rare condition that is usually seen in newborns with respiratory distress syndrome, overwhelming sepsis, meconium and other aspiration syndromes, intrauterine hypoxia and ischemia, and/or neonatal hypoxia and ischemia. This condition causes severe hypoxemia, and, as a result, has significant morbidity and mortality. Improved antenatal and neonatal care; the use of surfactant; continuous monitoring of oxygenation, blood pressure and other vital functions; and early recognition and intervention have made this condition even more rare. In modern neonatal intensive care units, anticipation and early treatment of PFC and its complications in sick newborns are commonplace. Thus, severe forms of PFC are only seen on isolated occasions. Consequently, it is even more imperative to revisit PFC compared with the time when there were occasional cases of PFC seen in neonatal intensive care units, and to discuss evolving treatment and management issues that pertain to this syndrome.

Direct recruitment of N-myc to target gene promoters.

The N-myc gene is amplified in 20-25% of human neuroblastomas, and this amplification serves as a poor prognostic factor. However, few genes have been determined to be direct targets of N-myc. Our current studies focused on identifying N-myc target genes, especially those affected in cells such as neuroblastomas that have high levels of N-myc protein. To pursue this goal, we performed differential expression screens with cell-culture systems containing high versus low levels of N-myc. The design of our experiments was such that we should identify genes both upregulated and downregulated by N-myc. Accordingly, we identified 22 genes upregulated by N-myc and one gene downregulated by N-myc. However, only five of these genes responded to increased N-myc levels in more than one system. Further analysis of the regulation of these genes required determining whether they were direct or indirect targets of N-myc. Therefore, we used a formaldehyde crosslinking and immunoprecipitation procedure to determine whether N-myc was bound to the promoters of these putative target genes in living cells. We found that low levels of N-myc were bound to the promoters of the telomerase and prothymosin genes in neuroblastoma cells having low amounts of N-myc but that the amounts of N-myc bound to these promoters greatly increased with overexpression of N-myc. However, the amount of max bound to the promoters was high before and after induction of N-myc. Therefore, our studies suggest that N-myc competes with other max partners for binding to target promoters. Our use of the chromatin immunoprecipitation assay suggests a molecular explanation for the consequences of amplification of the N-myc gene in neuroblastomas.

Direct examination of histone acetylation on Myc target genes using chromatin immunoprecipitation.

Overexpression of c-Myc can lead to altered transcriptional regulation of cellular genes and to neoplastic transformation. Although DNA binding is clearly required, the mechanism by which recruitment of c-Myc to target promoters results in transcriptional activation is highly debated. Much of this controversy comes from the difficulty in clearly defining a true Myc target gene. We have previously determined that cad is a bona fide Myc target gene and thus now use the cad promoter as a model to study Myc function. Others have shown that Myc can interact indirectly with histone acetylases and have suggested that Myc mediates transcriptional activation by causing an increase in the levels of acetylated histones on target promoters. To directly test this model, we employed a chromatin immunoprecipitation assay to examine the levels of acetylated histones on the cad promoter. Although Myc was bound to the cad promoter in S phase but not in G(0) phase, we found high levels of acetylated histones on the promoter in both stages. We also examined acetylated histones on the cad promoter before and after differentiation of U937 cells. Although the levels of c-Myc bound to the cad promoter were greatly reduced after differentiation, we saw high levels of acetylated histones on the cad promoter both before and after differentiation. Finally, we found that a 30-fold change in binding of N-Myc to the telomerase promoter did not result in a concomitant change in histone acetylation. Thus, recruitment of a Myc family member to a target promoter does not necessarily influence the amount of acetylated histones at that promoter. Further investigations are in progress to define the role of Myc in transcriptional activation.

Syphilis in an urban community.

Recent reports of changes in the epidemiology of syphilis prompted a review of syphilis in our urban community. All records of positive syphilis serology reported to the City of Scarborough Health Department between 1990-94 were reviewed for key epidemiological variables. While infectious stages of syphilis were reported more often among young adults, incidence for all stages increased among successive age groups, with a male/female ratio of 1.0. One in five cases were identified during immigration screening, with a disproportionate number of cases immigrating from the Caribbean, Africa and Subcontinental India. Overall, the incidence of syphilis decreased during the study. However, a correlation of 0.95 was found between the provincial incidence of syphilis and number of tests ordered. The observed decrease in syphilis, therefore, may represent a decrease in detection owing to lack of testing.

Improper office disposal of needles and other sharps: an occupational hazard outside of health care institutions.

An employee of a private disposal company suffered a finger needlestick injury while collecting waste at curbside from a building containing medical offices. Subsequent inspection of the contents of the garbage bags revealed the presence of used syringes and unsheathed needles. The Ministry of the Environment has developed a regulation and guidelines for the handling and disposal of biomedical waste including needles and other sharps. These specify that approved carriers and receivers are required for disposal; properly decontaminated waste is considered non-hazardous solid waste and can go to landfills. However, responsibility for curbside pickup of waste lies with municipalities; some municipalities have enacted by-laws which prohibit collection of this waste at the curbside. This incident illustrates that improper disposal of biomedical waste (including that from private practitioners' offices) may occur despite efforts to control its handling, and that needlestick injuries can occur outside of health care facilities among personnel who are not health care workers. Efforts are needed to increase the level of awareness among health professionals regarding their responsibility to ensure proper biomedical waste disposal from private offices. In addition, efforts should be made to bridge the gap between all levels of government regarding the disposal of biomedical waste.