A Possible Etiology of the Infertile 46XX Male Subject

We report on an infertile male patient with the predominant 46XX female karyotype. A testicular biopsy revealed widely separated testicular tubules, absence of sperm formation and large numbers of Leydig cells. Chromosome studies, including measurements of the X chromosomes, showed a significant difference between the lengths of the short arm of the 2 X chromosomes. This information lends support for an X-Y chromosome interchange as the etiology of this syndrome. The clinical features of this rare syndrome and other theories of etiology of XX male subjects are discussed

Inhibitor of growth-4 promotes IκB promoter activation to suppress NF-κB signaling and innate immunity

Ing4 is a member of the inhibitor of growth (ING) family of chromatin-modifying proteins. Biochemical experiments indicate that Ing4 is a subunit of the HB01-JADE-hEAF6 histone acetyltransferase complex responsible for most nucleosomal histone H4 acetylation in eukaryotes, and transfection studies suggest that Ing4 may regulate a wide variety of cellular processes, including DNA repair, apoptosis, cell-cycle regulation, metastasis, angiogenesis, and tumor suppression. However, in vivo evidence for a physiological role for Ing4 in cell-growth regulation is lacking. We have generated Ing4-deficient mice to explore the role of Ing4 in development, tumorigenesis, and in NF-κB signaling. Ing4-null mice develop normally and are viable. Although mice deficient for Ing4 fail to form spontaneous tumors, they are hypersensitive to LPS treatment and display elevated cytokine responses. Macrophages isolated from Ing4-null mice have increased levels of nuclear p65/RelA protein, resulting in increased RelA binding to NF-κB target promoters and up-regulation of cytokine gene expression. However, increased promoter occupancy by RelA in LPS-stimulated, Ing4-null cells does not always correlate with increased NF-κB target-gene expression, as RelA activation of a subset of cytokine promoters also requires Ing4 for proper histone H4 acetylation. Furthermore, activation of the IκBα promoter by RelA is also Ing4-dependent, and LPS-stimulated, Ing4-null cells have reduced levels of IκBα promoter H4 acetylation and IκB gene expression. Thus, Ing4 negatively regulates the cytokine-mediated inflammatory response in mice by facilitating NF-κB activation of IκB promoters, thereby suppressing nuclear RelA levels and the activation of select NF-κB target cytokines

Trials of providing information to general practitioners: a systematic review

ObjectiveTo determine if providing general practitioners (GPs) with costing information can change their clinical behaviour and reduce medical costs.Data sourcesMEDLINE, CINAHL, Health Plan and EMBASE and citations in review articles were searched for studies published between 1980 and 1996.Study selectionStudies were included if they provided costing information to GPs with the aim of decreasing costs by changing behaviour, included an objective measure of GP performance or clinical care, and used a randomised or quasi-randomised controlled design, crossover design or a controlled time series.Data extractionData extracted included study design, intervention used and measure of GP performance/clinical care (including test ordering, drug prescribing, hospital and primary care visits and costs).Data synthesisSix studies met the inclusion criteria. Computerised feedback on drug costs increased generic prescribing, and "academic detailing" decreased inappropriate prescribing of target drugs. Providing costing information also decreased ordering of diagnostic tests. "Gatekeeper" physicians reduced use of hospital and specialist services. Only two studies found the changes were sustained for nine months or longer and only one evaluated health outcomes.ConclusionThe provision of costing information can change GP behaviour in all service areas. Sustainability of these changes and linking of cost savings to health outcomes have not been well studied