Understanding the Genomic Structure of Copy-Number Variation of the Low-Affinity Fcγ Receptor Region Allows Confirmation of the Association of FCGR3B Deletion with Rheumatoid Arthritis.

Fcγ receptors are a family of cell-surface receptors that are expressed by a host of different innate and adaptive immune cells, and mediate inflammatory responses by binding the Fc portion of immunoglobulin G. In humans, five low-affinity receptors are encoded by the genes FCGR2A, FCGR2B, FCGR2C, FCGR3A, and FCGR3B, which are located in an 82.5-kb segmental tandem duplication on chromosome 1q23.3, which shows extensive copy-number variation (CNV). Deletions of FCGR3B have been suggested to increase the risk of inflammatory diseases such as systemic lupus erythematosus and rheumatoid arthritis (RA). In this study, we identify the deletion breakpoints of FCGR3B deletion alleles in the UK population and endogamous native American population, and show that some but not all alleles are likely to be identical-by-descent. We also localize a duplication breakpoint, confirming that the mechanism of CNV generation is nonallelic homologous recombination, and identify several alleles with gene conversion events using fosmid sequencing data. We use information on the structure of the deletion alleles to distinguish FCGR3B deletions from FCGR3A deletions in whole-genome array comparative genomic hybridization (aCGH) data. Reanalysis of published aCGH data using this approach supports association of FCGR3B deletion with increased risk of RA in a large cohort of 1,982 cases and 3,271 controls (odds ratio 1.61, P = 2.9×10-3 ).

Pattern of nosocomial infection in two intensive care units of a tertiary care hospital in Karachi.

OBJECTIVE: To determine the pattern of nosocomial infections in two ICUs' of a teaching hospital in terms of frequency, common sites of infection, the pathogens involved and the antibiotic sensitivity patterns. DESIGN: Observational study. PLACE AND DURATION OF STUDY: It was conducted in two medical ICUs (Neurology and Nephrology) of a public tertiary care hospital i.e. Civil Hospital, Karachi, from June to November 2004. PATIENTS AND METHODS: Data was collected prospectively on patients suspected to have developed nosocomial infection after 48 hours of admission to the ICU according to objective. RESULTS: There were 101 cases of suspected nosocomial infection out of a total of 254 patients. The frequency of nosocomial infection was 39.7%. UTI developed in 44.6%, while 27% had blood stream infection, and 21% had pneumonia. Each of the three major sites of infection was strongly associated with the use of invasive devices. Escherichia (E.) coli was the most common organism isolated followed by Pseudomonas aeruginosa and Klebsiella. E. coli and Klebsiella showed a maximum sensitivity to Imipenem followed by Tazocin (pipericillin + tazobactam). Pseudomonas aeruginosa was sensitive to Amikacin and Fosfomycin. CONCLUSION: The high frequency of nosocomial infection suggests that more strict measures regarding invasive devices should be taken in future to control the infection and limit the emergence of antibiotic resistant organisms.