Common variants near MC4R are associated with fat mass, weight and risk of obesity.

To identify common variants influencing body mass index (BMI), we analyzed genome-wide association data from 16,876 individuals of European descent. After previously reported variants in FTO, the strongest association signal (rs17782313, P = 2.9 x 10(-6)) mapped 188 kb downstream of MC4R (melanocortin-4 receptor), mutations of which are the leading cause of monogenic severe childhood-onset obesity. We confirmed the BMI association in 60,352 adults (per-allele effect = 0.05 Z-score units; P = 2.8 x 10(-15)) and 5,988 children aged 7-11 (0.13 Z-score units; P = 1.5 x 10(-8)). In case-control analyses (n = 10,583), the odds for severe childhood obesity reached 1.30 (P = 8.0 x 10(-11)). Furthermore, we observed overtransmission of the risk allele to obese offspring in 660 families (P (pedigree disequilibrium test average; PDT-avg) = 2.4 x 10(-4)). The SNP location and patterns of phenotypic associations are consistent with effects mediated through altered MC4R function. Our findings establish that common variants near MC4R influence fat mass, weight and obesity risk at the population level and reinforce the need for large-scale data integration to identify variants influencing continuous biomedical traits

Phaeohyphomycosis caused by Exophiala spinifera in two cats.

The dematiaceous fungus Exophiala spinifera was isolated from a cutaneous lesion on the paw of a male domestic shorthair cat and from the nasal exudate and abscess contents from a female domestic shorthair cat. Treatment with ketoconazole (10 mg kg daily) resulted in improvement in the first cat but unfortunately this animal was subsequently lost to follow-up. The second cat was treated initially by the same regimen without apparent benefit. The dose of ketoconazole was subsequently increased but finally had to be discontinued when the cat developed signs of hepatotoxicity. At this stage treatment with flucytosine (150 mg kg daily) was commenced. The cat improved and cultures of nasal exudate performed 8 and 16 weeks after initiation of 5-fluorocytosine therapy were negative for E. spinifera. However, the condition recurred with granulomatous tissue appearing in each nostril and abscess formation with subsequent rupture occurring on the bridge of the nose when therapy was withdrawn. These two cases constitute the first report of E. spinifera infection in animals and of this fungal infection in Australia

Persistent Neutrophilic Meningitis: REPORT OF FOUR CASES AND REVIEW OF THE LITERATURE

Neutrophilic (purulent) meningitis is characterized by hypoglycorrhachia, an elevated protien concentration, and a predominance of polymorphonuclear leukocytes in the cerebrospinal fluid (CSF) (86, 158). Bacteria are the major cause of this syndrom (86, 158) although a plethora of other uncommon infectious and noninfectious etiologies have been described (86, 158). Among the bacterial pathogens producing neutrophilic meningitis, Hemophilus influenzae, Streptococcus pneumoniae, Neisseria meningitidus and Group B streptococci account for the vast majority of cases (86, 111, 158). The initial management of neutrophilic meningitis usually consists of antimicrobial therapy directed against one or more of these common pathogens (86, 111, 158). Subsequent patient management may be modified by several factors, including clinical response to initial therapy, CSF culture results and results of additional CSF analyses

Early clinical and laboratory diagnosis of invasive pulmonary, extrapulmonary, and disseminated mucormycosis (zygomycosis)

Early diagnosis of invasive mucormycosis is important for timely therapeutic intervention, improved survival, and reduced morbidity. Given the importance of an accurate and rapid diagnosis of invasive mucormycosis to guide the timely initiation of amphotericin B and possible surgical intervention, a coordinated multidisciplinary approach of clinical assessment, diagnostic imaging, and laboratory assessment is necessary. Laboratory assessment for mucormycosis includes the conventional methods of direct examination and culture of tissue, respiratory secretions, bronchoalveolar lavage fluid, and other fluids. However, because conventional diagnostic tools are limited in their sensitivity, advanced molecular amplification systems, antigen detection assays, proteomic profiles, and metabolite detection may complement existing approaches to improve the rate of early diagnosis of invasive mucormycosis