Does the initiation of urate lowering treatment during an acute gout attack prolong the current episode and precipitate recurrent attacks: a systematic literature review

Objectives: To systematically review the literature on effect of initiating urate lowering treatment (ULT) during an acute attack of gout on duration of index attack and persistence on ULT. Methods: OVID (MEDLINE), EMBASE and AMED were searched to identify randomized controlled trials (RCTs) of ULT initiation during acute gout attack published in English language. Two reviewers appraised the study quality and extracted data independently. Standardised mean difference (SMD) and relative risk (RR) were used to pool continuous and categorical data. Meta-analysis was carried out using STATA v14. Results: 537 studies were selected. 487 titles and abstracts were reviewed after removing duplicates. Three RCTs were identified. There was evidence from two high quality studies that early initiation of allopurinol did not increase pain severity at days 10 to 15 (SMDpooled (95%CI) 0.18(-0.58, 0.93)). Data from three studies suggested that initiation of ULT during an acute attack of gout did not associate with drop-outs (RRpooled (95%CI) 1.16(0.58, 2.31)). Conclusion: There is moderate-quality evidence that the initiation of ULT during an acute attack of gout does not increase pain severity and risk of ULT discontinuation. Larger studies are required to confirm these findings so that patients with acute gout can be initiated on ULT with confidence

Low pH immobilizes and kills human leukocytes and prevents transmission of cell-associated HIV in a mouse model

BACKGROUND: Both cell-associated and cell-free HIV virions are present in semen and cervical secretions of HIV-infected individuals. Thus, topical microbicides may need to inactivate both cell-associated and cell-free HIV to prevent sexual transmission of HIV/AIDS. To determine if the mild acidity of the healthy vagina and acid buffering microbicides would prevent transmission by HIV-infected leukocytes, we measured the effect of pH on leukocyte motility, viability and intracellular pH and tested the ability of an acidic buffering microbicide (BufferGel(®)) to prevent the transmission of cell-associated HIV in a HuPBL-SCID mouse model. METHODS: Human lymphocyte, monocyte, and macrophage motilities were measured as a function of time and pH using various acidifying agents. Lymphocyte and macrophage motilities were measured using video microscopy. Monocyte motility was measured using video microscopy and chemotactic chambers. Peripheral blood mononuclear cell (PBMC) viability and intracellular pH were determined as a function of time and pH using fluorescent dyes. HuPBL-SCID mice were pretreated with BufferGel, saline, or a control gel and challenged with HIV-1-infected human PBMCs. RESULTS: Progressive motility was completely abolished in all cell types between pH 5.5 and 6.0. Concomitantly, at and below pH 5.5, the intracellular pH of PBMCs dropped precipitously to match the extracellular medium and did not recover. After acidification with hydrochloric acid to pH 4.5 for 60 min, although completely immotile, 58% of PBMCs excluded ethidium homodimer-1 (dead-cell dye). In contrast, when acidified to this pH with BufferGel, a microbicide designed to maintain vaginal acidity in the presence of semen, only 4% excluded dye at 10 min and none excluded dye after 30 min. BufferGel significantly reduced transmission of HIV-1 in HuPBL-SCID mice (1 of 12 infected) compared to saline (12 of 12 infected) and a control gel (5 of 7 infected). CONCLUSION: These results suggest that physiologic or microbicide-induced acid immobilization and killing of infected white blood cells may be effective in preventing sexual transmission of cell-associated HIV

Vulval elephantiasis as a result of tubercular lymphadenitis: two case reports and a review of the literature

<p>Abstract</p> <p>Introduction</p> <p>Elephantiasis as a result of chronic lymphedema is characterized by gross enlargement of the arms, legs or genitalia, and occurs due to a variety of obstructive diseases of the lymphatic system. Genital elephantiasis usually follows common filariasis and lymphogranuloma venereum. It may follow granuloma inguinale, carcinomas, lymph node dissection or irradiation and tuberculosis but this happens rarely. Vulval elephantiasis as a consequence of extensive lymph node destruction by tuberculosis is very rare. We present two very unusual cases of vulval elephantiasis due to tuberculous destruction of the inguinal lymph nodes.</p> <p>Case presentation</p> <p>Two Indian women - one aged 40 years and the other aged 27 years, with progressively increasing vulval swellings over a period of five and four years respectively - presented to our hospital. In both cases, there was a significant history on presentation. Both women had previously taken a complete course of anti-tubercular treatment for generalized lymphadenopathy. The vulval swellings were extremely large: in the first case report, measuring 35 × 25 cm on the right side and 45 × 30 cm on the left side, weighing 20 lb and 16 lb respectively. Both cases were managed by surgical excision with reconstruction and the outcome was positive. Satisfactory results have been maintained during a follow-up period of six years in both cases.</p> <p>Conclusions</p> <p>Elephantiasis of the female genitalia is unusual and it has rarely been reported following tuberculosis. We report two cases of vulval elephantiasis as a consequence of extensive lymph node destruction by tuberculosis, in order to highlight this very rare clinical scenario.</p

How managers can build trust in strategic alliances: a meta-analysis on the central trust-building mechanisms

Trust is an important driver of superior alliance performance. Alliance managers are influential in this regard because trust requires active involvement, commitment and the dedicated support of the key actors involved in the strategic alliance. Despite the importance of trust for explaining alliance performance, little effort has been made to systematically investigate the mechanisms that managers can use to purposefully create trust in strategic alliances. We use Parkhe’s (1998b) theoretical framework to derive nine hypotheses that distinguish between process-based, characteristic-based and institutional-based trust-building mechanisms. Our meta-analysis of 64 empirical studies shows that trust is strongly related to alliance performance. Process-based mechanisms are more important for building trust than characteristic- and institutional-based mechanisms. The effects of prior ties and asset specificity are not as strong as expected and the impact of safeguards on trust is not well understood. Overall, theoretical trust research has outpaced empirical research by far and promising opportunities for future empirical research exist

Expression of Snail2 in long bone osteosarcomas correlates with tumour malignancy

Snail2 is a marker of malignancy in epithelial tumours; however, in sarcomas, it is not known if this protein is present. Here we examine the expression of Snail2 in one type of sarcoma, osteosarcoma, and explore its relationship to tumour grade, subtype and anatomical location in cases of long bone and cranial bone osteosarcoma. Long bone osteosarcomas typically have a much greater metastatic capability and a poorer prognosis. We find that Snail2 is expressed in the three main subtypes of long bone osteosarcoma—osteoblastic, chondroblastic and fibroblastic. Regression analysis showed that Snail 2 expression was statistically correlated with tumour grade (p = 0.014) in all of these subtypes. Snail2 was only expressed in high-grade cranial bone osteosarcomas, suggesting a link between Snail2 expression and metastasis. This is the first time Snail2 has been associated with any sarcoma, and this study shows that Snail2 may be a useful prognostic marker for this disease

Health-related quality of life in adults reporting arthritis: analysis from the National Health Measurement Study

BackgroundArthritis is the leading cause of disability in the United States. We assess the generic health-related quality-of-life (HRQOL) among a nationally representative sample of U.S. adults with and without self-reported arthritis.MethodsThe NHMS, a cross-sectional survey of 3,844 adults (35-89 years) administered EuroQol-5D (EQ-5D), Health Utilities Index Mark 2 (HUI2) and 3 (HUI3), SF-36v2™, Quality of Well-being Scale self-administered form (QWB-SA), and the Health and Activities Limitations index (HALex) to each respondent via a telephone interview. Weighted multiple linear regression was used to generate age-gender-arthritis-stratified unadjusted HRQOL means and means adjusted for sociodemographic, socioeconomic covariates and comorbidities by arthritis-age category.ResultsThe estimated population prevalence of self-reported arthritis was 31%. People with arthritis were more likely to be woman, older, of lower socioeconomic status, and had more self-reported comorbidities than were those not reporting arthritis. Adults with arthritis had lower HRQOL on six different indexes compared with adults without arthritis, with overall differences ranging from 0.03 (QWB-SA, age-group 65-74) to 0.17 (HUI3, age-group 35-44; all P-value &lt; .05).ConclusionArthritis in adults is associated with poorer HRQOL. We provide age-related reference values for six generic HRQOL measures in people with arthritis

Prevalence of Cataract Surgery and Visual Outcomes in Indian Immigrants in Singapore: The Singapore Indian Eye Study

10.1371/journal.pone.0075584PLoS ONE810-POLN

Kinetic Analysis of Substrate Utilization by Native and TNAP-, NPP1-, or PHOSPHO1-Deficient Matrix Vesicles

During the process of endochondral bone formation, chondrocytes and osteoblasts mineralize their extracellular matrix by promoting the formation of hydroxyapatite seed crystals in the sheltered interior of membrane-limited matrix vesicles (MVs). Here, we have studied phosphosubstrate catalysis by osteoblast-derived MVs at physiologic pH, analyzing the hydrolysis of ATP, ADP, and PPi by isolated wild-type (WT) as well as TNAP-, NPP1- and PHOSPHO1-deficient MVs. Comparison of the catalytic efficiencies identified ATP as the main substrate hydrolyzed by WT MVs. The lack of TNAP had the most pronounced effect on the hydrolysis of all physiologic substrates. The lack of PHOSPHO1 affected ATP hydrolysis via a secondary reduction in the levels of TNAP in PHOSPHO1-deficient MVs. The lack of NPP1 did not significantly affect the kinetic parameters of hydrolysis when compared with WT MVs for any of the substrates. We conclude that TNAP is the enzyme that hydrolyzes both ATP and PPi in the MV compartment. NPP1 does not have a major role in PPi generation from ATP at the level of MVs, in contrast to its accepted role on the surface of the osteoblasts and chondrocytes, but rather acts as a phosphatase in the absence of TNAP. © 2010 American Society for Bone and Mineral Research

Overexpression of Inosine 5′-Monophosphate Dehydrogenase Type II Mediates Chemoresistance to Human Osteosarcoma Cells

overexpression in osteosarcoma patients with poor response to chemotherapy. The aim of this study was to provide evidence for direct involvement of IMPDH2 in the development of chemoresistance..IMPDH2 is directly involved in the development of chemoresistance in osteosarcoma cells, suggesting that targeting of IMPDH2 by RNAi or more effective pharmacological inhibitors in combination with chemotherapy might be a promising means of overcoming chemoresistance in osteosarcomas with high IMPDH2 expression