Risk Factors for Primary Middle East Respiratory Syndrome Coronavirus Illness in Humans,Saudi Arabia, 2014

Risk factors for primary Middle East respiratory syndrome coronavirus (MERS-CoV) illness in humans are incompletely understood. We identified all primary MERS-CoV cases reported in Saudi Arabia during March–November 2014 by excluding those with history of exposure to other cases of MERS-CoV or acute respiratory illness of unknown cause or exposure to healthcare settings within 14 days before illness onset. Using a case–control design, we assessed differences in underlying medical conditions and environmental exposures among primary case-patients and 2–4 controls matched by age, sex, and neighborhood. Using multivariable analysis, we found that direct exposure to dromedary camels during the 2 weeks before illness onset, as well as diabetes mellitus, heart disease, and smoking, were each independently associated with MERS-CoV illness. Further investigation is needed to better understand animal-to-human transmission of MERS-CoV.     

A comparison of EGF and MAb 528 labeled with 111In for imaging human breast cancer.

Our objective was to compare 111In-labeled human epidermal growth factor (hEGF), a 53-amino acid peptide with anti-epidermal growth factor receptor (EGFR) monoclonal antibody (MAb) 528 (IgG2a) for imaging EGFR-positive breast cancer. METHODS: hEGF and MAb 528 were derivatized with diethylenetriamine pentaacetic acid (DTPA) and labeled with 111In acetate. Receptor binding assays were conducted in vitro against MDA-MB-468 human breast cancer cells. Biodistribution and tumor imaging studies were conducted after intravenous injection of the radiopharmaceuticals in athymic mice bearing subcutaneous MCF-7, MDA-MB-231, or MDA-MB-468 human breast cancer xenografts or in severe combined immunodeficiency mice implanted with a breast cancer metastasis (JW-97 cells). MCF-7, MDA-MB-231, JW-97, and MDA-MB-468 cells expressed 1.5 x 10(4), 1.3 x 10(5), 2.7 x 10(5), and 1.3 x 106 EGFR/cell, respectively in vitro. RESULTS: 111In-DTPA-hEGF and 111In-DTPA-MAb 528 bound with high affinity to MDA-MB-468 cells (Ka of 7.5 x 10(8) and 1.2 x 10(8) L/mol, respectively). 111In-DTPA-hEGF was eliminated rapidly from the blood with < 0.2% injected dose/g (%ID/g) circulating at 72 h after injection, whereas 111In-DTPA-MAb 528 was cleared more slowly (3%ID/g in the blood at 72 h). Maximum localization of 111In-DTPA-hEGF in MDA-MB-468 tumors (2.2 %ID/g) was 10-fold lower than with 111In-DTPA-MAb 528 (21.6 %ID/g). There was high uptake in the liver and kidneys for both radiopharmaceuticals. Tumor-to-blood ratios were greater for 111In-labeled hEGF than for MAb 528 (12:1 versus 6:1), but all other tumor-to-normal tissue ratios were higher for MAb 528. MDA-MB-468 and JW-97 tumors were imaged successfully with both radiopharmaceuticals, but tumors were more easily visualized using 111In-labeled MAb 528. There was no direct quantitative relationship between EGFR expression on breast cancer cell lines in vitro, and tumor uptake of the radiopharmaceuticals in vivo, but control studies showed that tumor uptake was receptor mediated. CONCLUSION: Our results suggest that the tumor uptake in vivo of receptor-binding radiopharmaceuticals is controlled to a greater extent by their elimination rate from the blood than by the level of receptor expression on the cancer cells. Radiolabeled anti-EGFR MAbs would be more effective for tumor imaging in cancer patients than peptide-based radiopharmaceuticals such as hEGF, because they exhibit higher tumor uptake at only moderately lower tumor-to-blood ratios.     

Depletion of BAFF cytokine exacerbates infection in Pseudomonas aeruginosa infected mice

BackgroundCystic fibrosis (CF) is a genetic disease characterized by chronic inflammation of the lungs that is ineffective at clearing pathogens. B-cell activating factor (BAFF), a cytokine involved in the development of B-cells, is known to be elevated in CF patients with subclinical infections. We postulate that the elevated BAFF levels in CF patients might be triggered by Pseudomonas aeruginosa infection and it might play a protective role in the regulation of lung responses to infection.MethodsTo address this hypothesis, we used a well characterized model of CFTR.KO mice infected with a clinical strain of P. aeruginosa (PA508). We quantified cell types with flow cytometry, concentration of cytokines by ELISA tests, bacterial load by colony counting and lung physiology by metacholine-induced lung resistance.ResultsOur data demonstrates that BAFF is not elevated in uninfected CF mice, and infection with Pseudomonas leads to significant induction of this regulatory cytokine. We also demonstrate that the maintenance of BAFF levels and its induction during the infection is important for clearance of Pseudomonas infection as its depletion during the course of infection leads to decrease in the resolution of infection both in WT and CFTR-KO mice. Interestingly, the depletion of BAFF not only results in a depletion of B cells numbers but also to a significant decrease in the number of regulatory T cells in the non-infected lungs.ConclusionsOverall, our data demonstrate for the first time that BAFF is an important regulatory molecule helping to maintain the immunological response to infection and clearance of lung infection.     

RASSF1A methylation is predictive of poor prognosis in female breast cancer in a background of overall low methylation frequency

Breast cancer (BC) is the most common cancer worldwide. The Kingdom of Saudi Arabia is no exception, with ever increasing incidence rates. An interesting feature of this disease is the relatively young age of the affected women. The average age in the present cohort of 100 sporadic cases of invasive ductal carcinomas was 45 years, with a median of 46 years (range between 19-81 years). In an effort to understand the molecular signature of BC in the Saudi population, we undertook this study to profile the methylation events in a series of key genes including Ras association (RalGDS/AF-6) domain family member 1 isoform a (RASSF1A), hypermethylated in cancer 1 (HIC1), cyclin-dependent kinase inhibitor 2A (CDKN2A), retinoic acid receptor beta (RARB2), estrogen receptor 1 (ESR1), progesterone receptor (PGR), paired-like homeodomain 2 (PITX2), secreted frizzled-related protein 1 (SFRP1), myogenic differentiation 1 (MYOD1), and slit homolog 2 (SLIT2), using MethyLight analysis in archival tumour samples. Interestingly, the overall methylation levels were low in this cohort, with only 84% of the cases displaying methylation in one or more of the analysed genes. The frequency of RASSF1A methylation was the highest (65%), while there was almost complete absence of methylation of the ESR1 and the CDH1 genes (1% and 3%, respectively). Several statistically significant correlations were identified between specific methylation events and clinical parameters which gained more significance when analysis was limited to the estrogen receptor positive samples. Although there was no significant correlations between any methylation event and disease-specific survival, methylation of MYOD1 or RASSF1A was associated with lower disease-free survival and increased chance of disease recurrence. Furthermore, multivariate (Cox) regression analysis identified RASSF1A as an independent predictor of poor prognosis in terms of disease-free survival in this cohort. Our findings provide further evidence on the usefulness of RASSF1A methylation status as an informative prognostic biomarker in BC in a Saudi population.     

Procedural simulation: medical student preference and value of three task trainers for ultrasound guided regional anesthesia

BACKGROUND: Ultrasound guided regional anesthesia is widely taught using task trainer models. Commercially available models are often used; however, they can be cost prohibitive. Therefore, alternative "homemade" models with similar fidelity are often used. We hypothesize that professional task trainers will be preferred over homemade models. The purpose of this study is to determine realism, durability and cleanliness of three different task trainers for ultrasound guided nerve blocks.     

Prevalence and causes of blindness & low vision; before and five years after 'VISION 2020' initiatives in Oman: a review

BACKGROUND: A prevalence survey of blindness and low vision was conducted in Oman in 2005. Here, we present the prevalence and determinants of blindness and low vision among the population >or= 40 years of age. The results are then compared with those of the survey in 1997 and the changes following the 'VISION 2020' initiatives are assessed. METHODS: The survey covered 24 randomly selected clusters (75 houses in each). Teams assessed the distance vision of subjects while wearing glasses. The ophthalmologists examined the anterior segment and fundus to determine the causes of disability. The visual field was tested in those suspected of glaucoma. The prevalence rates of blindness (< 3/60 on presentation), legal blindness (< 6/60) and low vision (< 6/18) were calculated. The data from the 1997 survey was then analyzed to obtain similar rates in the population >or= 40 years of age. RESULTS: The prevalence of blindness was 8.25% (95% CI 7.14-9.36) in the >or= 40 year-old population in 2005. The rate would be 6.95% (95% CI 5.92-7.98) if blindness were defined as vision with best possible correction. The prevalence of legal blindness and low vision were 12% and 45.12%, respectively. In the 1997 survey, the prevalence of blindness in same age group was 7.23% (95% CI 5.91-8.55). Between the two surveys, the prevalence of blindness due to corneal pathology declined from 1.9% to 1.1% but that of blindness due to unoperated cataract increased from 1.8% to 2.3%. CONCLUSIONS: The rate of disability has declined but the number of blind people has increased in Oman. The causes of blindness have changed from communicable/avoidable eye diseases to non-curable/chronic eye diseases, and the number with visual disabilities has increased. An increasing number of operations for cataract and improvements in the care for glaucoma and diabetic retinopathy are recommended.     

Priming with anticholinesterases — the effect of different priming doses of edrophonium

The effect of different priming doses of edrophonium were studied in 77 patients divided into seven groups (n = 11 in each). Edrophonium 1.0 mg.kg-1 was administered either in a single bolus dose (Group I; controls) or in an initial dose of 0.05, 0.1, 0.15, 0.2, 0.25 or 0.3 mg.kg-1 followed one minute later by the remainder of the 1.0 mg.kg-1 dose in Groups II to VII respectively. Reversal was attempted at ten per cent spontaneous recovery of twitch height (T1) from atracurium-induced neuromuscular blockade. Increasing the size of the priming dose from 0.05 to 0.2 mg.kg-1 resulted in a stepwise increase (p less than 0.05) in recovery of T1 and train-of-four (TOF) ratio. Higher priming doses (0.25 and 0.3 mg.kg-1) were not associated with further improvement in T1 and TOF recovery. Reversal time, that is the time taken from the first injection of edrophonium until the TOF ratio value had reached 0.75 was significantly faster (p less than 0.01) following priming with edrophonium 0.2 mg.kg-1 (Group V) when compared to Groups I, II, III, IV and VI. Reversal times were also significantly faster in Groups IV and VI when compared to the control group. It is concluded that 0.2 mg.kg-1 appears to be the optimal priming dose for administration of edrophonium in divided doses.