BACKGROUND: Systemic lupus erythematosus (SLE) is a complex autoimmune disorder with multiple susceptibility genes. We have previously reported suggestive linkage to the chromosomal region 14q21-q23 in Finnish SLE families. PRINCIPAL FINDINGS: Genetic fine mapping of this region in the same family material, together with a large collection of parent affected trios from UK and two independent case-control cohorts from Finland and Sweden, indicated that a novel uncharacterized gene, MAMDC1 (MAM domain containing glycosylphosphatidylinositol anchor 2, also known as MDGA2, MIM 611128), represents a putative susceptibility gene for SLE. In a combined analysis of the whole dataset, significant evidence of association was detected for the MAMDC1 intronic single nucleotide polymorphisms (SNP) rs961616 (P -value = 0.001, Odds Ratio (OR)= 1.292, 95% CI 1.103-1.513) and rs2297926 (P -value = 0.003, OR = 1.349, 95% CI 1.109-1.640). By Northern blot, real-time PCR (qRT-PCR) and immunohistochemical (IHC) analyses, we show that MAMDC1 is expressed in several tissues and cell types, and that the corresponding mRNA is up-regulated by the pro-inflammatory cytokines tumour necrosis factor alpha (TNF-alpha) and interferon gamma (IFN-gamma) in THP-1 monocytes. Based on its homology to known proteins with similar structure, MAMDC1 appears to be a novel member of the adhesion molecules of the immunoglobulin superfamily (IgCAM), which is involved in cell adhesion, migration, and recruitment to inflammatory sites. Remarkably, some IgCAMs have been shown to interact with ITGAM, the product of another SLE susceptibility gene recently discovered in two independent genome wide association (GWA) scans. SIGNIFICANCE: Further studies focused on MAMDC1 and other molecules involved in these pathways might thus provide new insight into the pathogenesis of SLE.

Despite extensive research on the bottom-up force of resource availability (e.g., electron donors and acceptors), slow biodegradation rates and stalling at cis-dichloroethene (cDCE) and vinyl chloride (VC) continue to be observed in aquifers contaminated with trichloroethene (TCE). The objective of this research was to gauge the impact of the top-down force of protistan predation on TCE biodegradation in laboratory microcosms. When indigenous bacteria from an electron donor limited TCE contaminated bedrock aquifer were present, the indigenous protists inhibited reductive dechlorination altogether. The presence of protists during organic carbon-amended conditions caused the bacteria to elongate (length:width >/= 10:1), but reductive dechlorination was still inhibited. When a commercially-available dechlorinating bacterial culture and an organic carbon amendment were added in the presence of protists, the elongated bacteria predominated and reductive dechlorination stalled at cDCE. When protists were removed under organic carbon-amended conditions, reductive dechlorination stalled at cDCE; whereas in the presence organic carbon and bacterial amendments, the total chlorinated ethene concentration decreased, indicating TCE was converted to ethene and/or CO2. The data suggested that indigenous protists grazed dechlorinators to extremely low levels, inhibiting dechlorination altogether. Hence, in situ bioremediation/bioaugmentation may not be successful in mineralizing TCE unless the top-down force of protistan predation is inhibited.

OBJECTIVE: To discuss the surgical technique and evaluate the effectiveness of external auditory canal (EAC) closure in patients with refractory chronically draining ears. STUDY DESIGN AND SETTING: A retrospective case review of seven patients who underwent EAC closure for chronically draining ears at a private tertiary otologic referral center between 2001 and 2004. Three patients underwent concomitant placement of a BAHA implant, and one patient underwent cochlear implantation during a second-stage procedure. RESULTS: All seven patients had successful closure of the external auditory canal with elimination of chronic drainage. The follow-up interval ranged from 10 to 35 months. There were no cases of iatrogenic cholesteatoma formation or breakdown of the ear canal closure. CONCLUSION AND SIGNIFICANCE: In patients with refractory chronically draining ears, EAC closure, alone or in conjunction with a bone-anchored implant, may be a treatment option. A BAHA implant can be placed during the initial procedure or staged.

ABSTRACT: A sample of addictions agencies' staff in Ontario were interviewed by telephone to assess attitudes toward, anticipated internal and external barriers to implementing, and expected benefits of four harm reduction strategies: needle exchange, moderate drinking goals, methadone treatment, and provision of free condoms to clients. Respondents were also asked to define harm reduction, list its most important elements, and describe what they find most troubling and most appealing about harm reduction. Attitudes toward harm reduction in general and the services provided at each agency were also assessed. Results indicated that the service providers surveyed had positive attitudes toward each of the four harm reduction strategies and harm reduction in general, and the majority of respondents were aware of the benefits associated with each strategy. Almost all of the agencies surveyed allowed for moderate drinking outcomes in the treatment of alcohol problems, and most agencies provided free condoms to clients. In terms of barriers, anticipated negative community reaction to needle exchange, methadone treatment, and free condoms was a major concern for the majority of respondents. Lack of staff, of funding, or anticipated staff resistance were also cited as potential barriers to introducing these strategies. In the case of methadone maintenance, the unavailability of a qualified physician was listed as the primary constraint. Implications for future efforts directed at encouraging the adoption of these strategies are discussed.

Defects in the maxillofacial region may result from many causes, including injury and tumor excision. Such defects must be repaired as completely as possible so that the best possible restoration of function and cosmesis can be achieved. Calcium phosphate cements (CPCs) are a blend of amorphous and crystalline compounds that are used in paste form and become solid HA when they set. This article will review literature regarding various types if CPCs, their application to maxillofacial surgery, and the contraindications and complications associated with their use.

Collision induced dissociation (CID) in a quadrupole ion trap mass spectrometer using the conventional 30 ms activation time is compared with high amplitude short time excitation (HASTE) CID using 2 ms and 1 ms activation times. As a result of the shorter activation times, dissociation of the parent ions using the HASTE CID technique requires resonance excitation voltages greater than conventional CID. After activation, the rf trapping voltage is lowered to allow product ions below the low mass cut-off to be trapped. The HASTE CID spectra are notably different from those obtained using conventional CID and can include product ions below the low mass cut-off for the parent ions of interest. The MS/MS efficiencies of HASTE CID are not significantly different when compared with the conventional 30 ms CID. Similar results were obtained with a two-dimensional (linear) ion trap and a three-dimensional ion trap.

BACKGROUND:: To describe the prevalence, clinical features, and causes of vision loss among patients with ocular toxocariasis seen at a uveitis referral center. METHODS:: A review was completed of the charts of patients with ocular toxocariasis who were examined between 1977 and 1996 at the Francis I. Proctor Foundation of the University of California at San Francisco. The prevalence of ocular toxocariasis among all uveitis patients seen at the center was determined. Demographic features, symptoms, and signs in all patients were evaluated. RESULTS:: Ocular toxocariasis occurred in 22 (1.0%) of 2,185 uveitis patients. The mean patient age was 16.5 years. Inflammation was usually unilateral (90.9%). Toxocara uveitis presented as a granuloma in the peripheral retina in 50% of cases, as a granuloma in the macula in 25% of cases, and as a moderate to severe vitreous inflammation mimicking endophthalmitis in 25% cases. The primary causes of vision loss were vitritis (52.6%), cystoid macular edema (47.4%), and traction retinal detachment (36.8%). CONCLUSIONS:: Ocular toxocariasis is an uncommon cause of uveitis that mainly affects younger patients. Inflammation is typically unilateral and presents as either a granuloma in the peripheral or posterior retina or a moderate to severe vitreous inflammation mimicking endophthalmitis.

BACKGROUND CONTEXT: Symptomatic spinal epidural lipomatosis (SEL), a rare cause of spinal cord compression, has most often been associated with exogenous steroid use. PURPOSE: Identify four associations with SEL, correlate the associated groups with level of disease and compare treatment with outcome data in these groups. STUDY DESIGN/SETTING: Case reports of three patients and analysis of 104 cases from the literature. PATIENT SAMPLE: Three patients from the senior author's practice. OUTCOME MEASURES: Not applicable. METHODS: The authors report three new cases of SEL not associated with steroid use. They review all available English literature and present a table of all 104 reported cases. RESULTS: The clinical course of three new patients is reported. CONCLUSIONS: Associated conditions are exogenous steroid use, obesity, endogenous steroid excess, and some remain idiopathic. Although SEL is a rare condition, our review of the literature reveals many more reported cases than previously thought. With increased awareness of this condition and improved imaging techniques, further studies of this disease should be undertaken.

OBJECTIVE: Innovations in diagnosis, surgical techniques, and perioperative care have dramatically improved outcomes in lateral skull base procedures in recent years. There is a belief, however, that children with skull base tumors have yet to benefit from these technological and procedural advances. The purpose of this study is to provide a clinical review of neurotologic skull base surgery in the pediatric population. STUDY DESIGN: Retrospective case review. SETTING: Private practice tertiary referral center. PATIENTS: Eighty-nine pediatric patients undergoing 115 neurotologic procedures for lateral skull base tumors from July 1992 to September 2003. MAIN OUTCOME MEASURES: Initial clinical presentation, tumor type, pre- and postoperative hearing and facial nerve status, treatment course, complications, and functional outcomes. RESULTS: The majority of tumors in this series were vestibular schwannomas, and 65 patients were diagnosed with neurofibromatosis Type 2. Surgical approaches included 70 middle fossa, 40 translabyrinthine, 2 transcochlear, 2 infratemporal fossa, and 1 retrosigmoid craniotomy. Complete tumor removal was accomplished in the majority of cases (97%), with good preservation of facial nerve function (House-Brackmann Grade I or II) in 80% of patients. In patients undergoing middle fossa surgery for hearing preservation, measurable hearing was preserved in 61.4% of cases. The incidence of complications was low. CONCLUSION: With advances in diagnostic procedures and use of current neurotologic techniques, pediatric patients may undergo successful treatment of lateral skull base tumors, with good functional outcomes and minimal morbidity.