Neonatal disseminated methicillin-resistant Staphylococcus aureus presenting as orbital cellulitis

Orbital cellulitis and abscess are known complications of ethmoiditis in children, but they are very rare in the newborn. The authors report a case of orbital abscess caused by methicillin-resistant Staphylococcus aureus (MRSA) in a four-week-old neonate born four weeks prematurely.     

Generation X: implications for faculty recruitment and development in academic health centers.

Differences and tensions between the Baby Boom generation (born 1945-1962) and Generation X (born 1963-1981) have profound implications for the future of academic medicine. By and large, department heads and senior faculty are Boomers; today's residents and junior faculty are Generation X'ers. Looking at these issues in terms of the generations involved offers insights into a number of faculty development challenges, including inadequate and inexpert mentoring, work-life conflicts, and low faculty morale. These insights suggest strategies for strengthening academic medicine's recruitment and retention of Generation X into faculty and leadership roles. These strategies include (1) improving career and academic advising by specific attention to mentoring "across differences"--for instance, broaching the subject of formative differences in background during the initial interaction; adopting a style that incorporates information-sharing with engagement in problem solving; offering frequent, frank feedback; and refraining from comparing today to the glories of yesterday; to support such improvements, medical schools should recognize and evaluate mentoring as a core academic responsibility; (2) retaining both valued women and men in academic careers by having departments add temporal flexibility and create and legitimize less-than-full-time appointments; and (3) providing trainees and junior faculty with ready access to educational sessions designed to turn their "intellectual capital" into "academic career capital."Given the trends discussed in this article, such supports and adaptations are indicated to assure that academic health centers maintain traditions of excellence.     

Fine mapping and evaluation of candidate genes for cervical cancer on 11q23

We previously showed that loss of heterozygosity (LOH) at 11q23 is a common genetic alteration in cervical cancer (CC) and that it correlates with extensive invasion of lymph-vascular spaces. In the current study, we looked for allelic loss in paired normal/tumor genomic DNA from 121 cervical tumors by using 20 well-mapped microsatellite markers on 11q. LOH at one or more loci was observed in 81 (66.9%) tumors. The deletion patterns in tumors are complex. However, at least three LOH islands could be defined between D11S614 and D11S4167. We also genotyped 11 CC cell lines and analyzed the results using the homozygosity mapping-of-deletions method. Five of the 11 cell lines showed continuous homozygosity that extended through 11q23.3-11q24.1. We used a candidate-gene approach to screen candidate tumor-suppressor genes (TSGs) that were localized in that region. Intragenic changes in the entire coding sequence of four candidate genes (RNF26, USP2, POU2F3, and TRIM29) in the region and a proposed TSG (PPP2R1B) centromeric to the region were evaluated. The expression status of USP2, POU2F3, TRIM29, and another proposed TSG that is telomeric to the region (BCSC1) also was examined. We identified previously described single-nucleotide polymorphisms (SNPs), several novel variants, and three rare SNPs in the five candidate genes. Decreased expression of POU2F3 and TRIM29 was found in some cervical tumors and CC cell lines. Our results indicate that a major region of LOH in cervical cancer exists within a 3.6-Mb stretch of DNA on 11q23.3-q24.1 and that somatic mutations in RNF26, USP2, TRIM29, POU2F3, or PPP2R1B probably are not important for cervical carcinogenesis.     

Transient phenomena in learning and evolution: genetic assimilation and genetic redistribution

Deacon has recently proposed that complexes of genes can be integrated into functional groups as a result of environmental changes that mask and unmask selection pressures. For example, many animals endogenously synthesize ascorbic acid (vitamin C), but anthropoid primates have only a nonfunctional version of the crucial gene for this pathway. It is hypothesized that the loss of functionality occurred in the evolutionary past when a diet rich in vitamin C masked the effect of the gene, and its loss effectively trapped the animals in a fruit-eating lifestyle. As a result, the complex of abilities that support this lifestyle were evolutionarily bound together, forming a multilocus complex. In this study we use evolutionary computation simulations to explore the thesis that masking and unmasking can transfer dependence from one set of genes to many sets, and thereby integrate the whole complex of genes. We used a framework based on Hinton and Nowlan's 1987 simulation of the Baldwin effect. Additional gene complexes and an environmental parameter were added to their basic model, and the fitness function extended. The simulation clearly demonstrates that the genetic redistribution effect can occur in silico, showing an initial advantage of endogenously synthesized vitamin C, followed by transfer of the fitness contribution to the complex of genes that together allow the acquisition of vitamin C from the environment. As is well known in the modeling community, the Baldwin effect only occurs in simulations when the population of agents is 'poised on the brink' of discovering the genetically specified solution. Similarly, the redistribution effect occurs in simulations under specific initial conditions: too little vitamin C in the environment, and its synthesis it is never fully masked; too much vitamin C, and the abilities required to acquire it are not tightly integrated. The Baldwin effect has been hypothesized as a potential mechanism for developing language-specific adaptations like innate universal grammar and other highly modular capacities. We conclude with a discussion of the relevance of genetic assimilation and genetic redistribution to the evolution of language and other cognitive adaptations.     

The linkage disequilibrium maps of three human chromosomes across four populations reflect their demographic history and a common underlying recombination pattern

The extent and patterns of linkage disequilibrium (LD) determine the feasibility of association studies to map genes that underlie complex traits. Here we present a comparison of the patterns of LD across four major human populations (African-American, Caucasian, Chinese, and Japanese) with a high-resolution single-nucleotide polymorphism (SNP) map covering almost the entire length of chromosomes 6, 21, and 22. We constructed metric LD maps formulated such that the units measure the extent of useful LD for association mapping. LD reaches almost twice as far in chromosome 6 as in chromosomes 21 or 22, in agreement with their differences in recombination rates. By all measures used, out-of-Africa populations showed over a third more LD than African-Americans, highlighting the role of the population's demography in shaping the patterns of LD. Despite those differences, the long-range contour of the LD maps is remarkably similar across the four populations, presumably reflecting common localization of recombination hot spots. Our results have practical implications for the rational design and selection of SNPs for disease association studies.     

Reproductive decision-making among HIV-Infected women

OBJECTIVE: To describe factors related to reproductive decision-making among HIV-infected women. MATERIALS AND METHODS: A sample of HIV-infected women (N=104) who received care at an HIV clinic in the southern United States were interviewed about their reproductive decision-making. Women who became pregnant subsequent to HIV diagnosis were compared to women who did not become pregnant, and women who underwent a sterilization procedure subsequent to HIV diagnosis were compared to women who did not get sterilized. RESULTS: Compared to women who did not get pregnant after receiving an HIV diagnosis, women who became pregnant were more likely to be young, single, diagnosed earlier in the epidemic and to have more recently used a noninjecting drug. Among women who did not get pregnant, 63% reported their diagnosis greatly affected that decision. Having a partner who wants more children was not associated with pregnancy. Compared to women who did not get sterilized after learning their HIV status, women who did get sterilized tended to be Baptist and already had a prior live birth. Neither a woman's desire nor her partner's desire for more children was associated with sterilization. CONCLUSIONS: HIV is an important influence on HIV-infected women's reproductive choices, regardless of the decision being made. Reproductive counseling by HIV care providers needs to be sensitive to all the issues faced by these women.     

Immune dysregulation in allergic respiratory disease: the role of T regulatory cells

Although earlier research focused on the role of the polarity of T helper cell signalling as the defining factor in immune responses, it is now recognised that other cells with regulatory properties have a more key role. It has been recently proposed that allergic disease may result from an inappropriate balance between regulatory cells (including but not limited to CD4+ CD25+ T regulatory cells) and T helper type 2 (Th2) effector cells. In the airways, a number of other cells also have important regulatory effects on local immune responses, including epithelial cells and airway dendritic cells (DC). Allergic respiratory disease appears to be the culmination of both local epithelial dysfunction and generalised immune dysregulation resulting in Th2 propensity (atopic predisposition). Although these processes are related they also appear to occur independently. This review examines evolving models of allergy pathogenesis, including the newly recognised role of diverse groups of regulatory cells. Increasing rates of allergic disease (and other immune diseases) suggest that environmental changes may be having fundamental effects on common regulatory pathways. Understanding these influences and their mechanism of action could lead to strategies to prevent disease.     

Prevalence of self-reported high blood pressure awareness, advice received from health professionals, and actions taken to reduce high blood pressure among US adults--Healthstyles 2002

High blood pressure awareness, advice received from health care providers, and adoption of heart-healthy behaviors were assessed using the Healthstyles 2002 survey. About 20% of respondents reported that they had high blood pressure, and 53% of these were currently taking medications to lower blood pressure. Black men had the highest adjusted prevalence of high blood pressure (32%). Medication use among persons with high blood pressure was lower among Hispanics (45%) than among blacks (54%) and whites (54%). Persons reporting having high blood pressure were five times more likely to report having received advice from a health care professional to go on a diet or change eating habits (p<0.05) and reduce salt or sodium in their diet (p<0.05), but five times less likely to have received advice to exercise (p<0.05) than those reporting not having high blood pressure, after adjustment for differences in sex, race/ethnicity, and age. Persons with self-reported high blood pressure were also more likely to be making these modifications (p<0.05). Among people with high blood pressure, current medication use was associated with both receiving and following advice for diet change and salt reduction (p<0.05). Future initiatives are needed to improve the proportion of Hispanics and blacks taking prescribed medications to improve high blood pressure control and reduce risk for serious sequelae such as heart disease and stroke.     

The management of type 2 diabetes mellitus in children and adolescents

The medical community faces an emerging epidemic of type 2 diabetes mellitus (DM2) in children and adolescents with a disproportionate increase among certain ethnic groups. DM2 represents one arm of the metabolic syndrome and parallels an increasing prevalence of obesity. The metabolic syndrome includes insulin resistance, hyperlipidemia, and hypertension with a consequent risk of early cardiovascular disease. Thus, treatment of DM2 and the metabolic syndrome poses a challenge for pediatric endocrinologists and represents a huge public health issue. This review presents information about treatment of childhood DM2 with emphasis on indications for the use of insulin in management and normalization of blood glucose.     

Neutropenia following IVIG therapy in pediatric patients with immune-mediated thrombocytopenia

It has been observed that some children with immune-mediated thrombocytopenia (ITP) who are treated with intravenous immunoglobulin (IVIG) experience a decline in their absolute neutrophil count (ANC). The aim of this study was to investigate the incidence of neutropenia following IVIG therapy in a large cohort of children with ITP. This retrospective comparative cohort study determined the incidence of neutropenia in 104 patients (110 treatment courses) admitted for ITP to the Children's Hospital of Philadelphia from January 2000 to October 2003. Post-treatment ANCs were compared between patients who received IVIG and patients who received anti-D immunoglobulin. The incidence of neutropenia in each group was analyzed using the Fisher exact test. Pretreatment ANCs were not significantly different between the two treatment groups (P = 0.72). Neutropenia (ANC < 1,500/microL), developed during 18 of 64 (28%) treatment courses with IVIG, compared with 0 of 46 (0%) treatment courses with anti-D immunoglobulin (P < 0.001). This study suggests that IVIG may cause neutropenia commonly in children with ITP. While this is likely to be a transient condition, its recognition may affect clinical decisions such as the need for a bone marrow examination.