136 research outputs found

    Cross-sectional study of nutritional intake among patients undergoing tuberculosis treatment along the Myanmar-Thailand border

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    OBJECTIVE: This study summarises nutritional intake among patients with tuberculosis (TB) along the Myanmar-Thailand border according to the local diet. SETTING: TB clinic along the Myanmar-Thailand border. PARTICIPANTS: Cross-sectional surveys of 24-hour food recall were conducted with participants receiving anti-TB treatment. Participants were purposively selected to reflect proportion of age, sex and HIV co-infection based on historical patient records. Out of a total of 28 participants, 20 (71.4%) were men and 5 (17.9%) were co-infected with HIV. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome compared actual recorded intake to recommended intake. Secondary outcomes compared weight gain and body mass index (BMI) from diagnosis to time of survey. RESULTS: There were no significant differences in macronutrient or micronutrient intake by sex or for patients supplementing their rations. Mean treatment length at time of survey was 20.7 weeks (95% CI: 16.5 to 24.8). A significantly higher proportion of women (8/8, 100%) met caloric requirements compared with men (9/20, 45.0%, p=0.010), but few participants met other macronutrient or micronutrient requirements, with no significant differences by sex or for patients supplementing their rations. From diagnosis to the time of the survey, participants averaged significant weight gain of 6.48 kg (95% CI: 3.87 to 9.10) and increased BMI of 2.47 kg/m(2) (95% CI: 1.45 to 3.49; p=0.0001 for both). However, 50% (14/28) still had mild or more severe forms of malnutrition. CONCLUSIONS: This cross-sectional survey of nutritional intake in patients undergoing TB treatment in a sanatorium setting demonstrates the difficulty in sufficiently meeting nutritional demands, even when providing nutritional support

    Evaluation of LOXL1 gene polymorphisms in exfoliation syndrome and exfoliation glaucoma

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    Purpose: To evaluate genetic susceptibility of lysyl oxidase-like 1 (LOXL1) gene polymorphisms to exfoliation syndrome (XFS) and exfoliation glaucoma (XFG) in a case-control cohort of American and European patients. Methods: DNA from a total of 620 individuals including 287 exfoliation patients and 333 healthy control subjects were extracted by standard methods. Three single nucleotide polymorphisms (SNPs) of rs1048661 (R141L), rs3825942 (G153D), and rs2165241 were genotyped in these individuals by SNaPshot Assay. The seven coding exons of the LOXL1 gene and their immediate flanking regions were directly sequenced in 95 affected patients. Data management and case-control association studies were performed with SNP-STAT and PLINK programs. The obtained DNA sequences were evaluated with the STADEN package. Results: The 287 unrelated exfoliation cases comprised of 171 American patients (mostly of European background) and 116 patients from 12 European countries. This phenotype was further divided into patients with exfoliation only and no glaucoma (XFO; n=95), exfoliation with glaucoma (XFG; n=133), and exfoliation unclassified (XFU; n=59). Genotypic data were analyzed separately for XFO, XFG, XFU, and XFS (all exfoliations; n=287) and for Americans and Europeans. The observed genotypic frequencies for each exfoliation phenotype or population were tabulated separately and tested for deviation from the Hardy–Weinberg equilibrium (HWE) using a standard Χ2 test. There were no HWE deviations and no significant genotypic differences between these subcategories for the three studied SNPs. For the combined exfoliation cohort, homozygote genotypes of G/G (rs1048661), G/G (rs3825942), and T/T (rs2165241) were significantly overrepresented. Likewise, case-control allelic association for rs1048661 (p=7.74x10−9), rs3825942 (p=3.10x10−17), and rs2165241 (p=4.85x10−24) were highly significant. The corresponding two-locus haplotype frequencies of GG for rs1048661-rs3825942 (p=1.47x10−27), GT for rs1048661-rs2165241 (p=1.29x10−24), and GT for rs3825942-rs2165241 (p=2.02x10−24) were highly associated with exfoliation phenotypes. The combined effect of these three SNPs revealed that the GGT haplotype is overrepresented by 66% in exfoliation cases, and this deviation from controls is highly significant (p=1.93x10−24). This haplotype constituted a major risk factor for development of exfoliation in both XFS and XFG. By contrast, the GAC haplotype was significantly underrepresented (p=4.99x10−18) in exfoliation cases by 83% and may potentially have a protective effect for this condition with an estimated attributable risk percent reduction of 457%. The only other haplotype that was significantly different between cases and controls was TGC (p=5.82x10−9). No observation was made for the GAT haplotype. The combined three haplotypes of GGT, GAC, and TGC were associated with 91% of the exfoliation syndrome cases in the studied populations. Seven coding exons of LOXL1 were also sequenced in 95 affected cases. In addition to the three above-mentioned SNPs, 12 other variations were also observed in these patients(G240G, D292D, A320A, V385V, rs2304719, IVS3+23C>T, IVS3–155G>A, IVS3–101G>A, IVS4+49G>A, rs2304721, IVS5–121C>T, and rs2304722). None were considered a disease-causing mutation. Conclusions: We confirmed a strong association with LOXL1 variants in our patients. For the LOXL1 gene, individual alleles of rs1048661 (G), rs3825942 (G), and rs2165241 (T) are highly associated with XFS and XFG in American and European populations. The GGT haplotype constitutes a major risk haplotype for exfoliation, and GAC may have a protective role. DNA sequencing of 95 affected patients did not show any mutations in this gene. The LOXL1 SNPs are located in the 15q24.1 band and within a genetic locus (GLC1N) that is associated with primary open-angle glaucoma (POAG). However, the LOXL1 genetic predisposition is only limited to exfoliation with or without glaucoma and does not include the POAG phenotype

    Quantitative DNA pooling to increase the efficiency of linkage analysis in autosomal dominant disease

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    DNA pooling is an efficient method to rapidly perform genome-wide linkage scans in autosomal recessive diseases in inbred populations where affected individuals are likely to be homozygous for alleles near the disease gene locus. We wanted to examine whether this approach would detect linkage in autosomal dominant (AD) disorders where affected individuals may share one allele identical by descent at loci tightly linked to the disease. Two large outbred pedigrees in which the AD diseases familial venous malformation (FVM) and hereditary hemorrhagic telangiectasia (HHT1), linked to 9p and 9q, respectively, were investigated. Separate pools of DNA from affected ( n = 21 for FVM and 17 for HHT1) and unaffected family members ( n = 9 FVM and HHT1), and 25 unrelated population controls were established. Polymorphic markers spanning chromosome 9 at approximately 13.5-cM intervals were amplified using standard PCR. Allele quantitation was performed with a fluorimager. Visual inspection of allele intensities and frequency distributions suggested a shift in frequency of the most common allele in the affecteds lane when compared to control lanes for markers within 30 cM of the FVM and HHT1 loci. These subjective assessments were confirmed statistically by testing for the difference between two proportions (one-sided; P ≤ 0.05). When using population controls, the true-positive rates for FVM and HHT1 were 5/5 and 2/5 markers, respectively. False-positive rates for FVM and HHT1 were 3/9 and 2/9, respectively. In both AD diseases investigated, quantitative DNA pooling detected shifts in allele frequency, thus identifying areas of known linkage in most cases. The utility of this technique depends on the size of the pedigree, frequency of the disease-associated allele in the population, and the choice of appropriate controls. Although the false-positive rate appears to be high, this approach still serves to reduce the amount of overall genotyping by about 60%. DNA pooling merits further investigation as a potential strategy in increasing the efficiency of genomic linkage scans.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/42260/1/439-102-2-207_81020207.pd

    Indications and outcome of repeat penetrating keratoplasty in India

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    BACKGROUND: Repeat penetrating keratoplasty is quite often required as there is high chance of failure of the primary graft particularly in the developing world. We planned a study to analyze the indications and outcome of repeat penetrating keratoplasty in a tertiary care centre in India. METHODS: A retrospective analysis of all the patients who underwent repeat penetrating keratoplasty, between January 1999 and December 2001 was performed. The parameters evaluated were indication for the primary penetrating keratoplasty, causes of failure of the previous graft, and final visual outcome and clarity of the repeat corneal grafts. RESULTS: Of fifty-three eyes of 50 patients with repeat penetrating keratoplasty (three patients underwent bilateral corneal regrafts), 37 eyes had undergone one regraft each, 14 eyes two regrafts and two eyes had three regrafts. The follow-up of the patients ranged from one to three years. The most common primary etiologic diagnosis was vascularized corneal scars (66%), of which the scars related to infection were most common (68.5%). Twenty-eight regrafts (52.8%) remained clear at a mean follow-up of 1.54 ± 0.68 years, of which 25 were single regrafts (89.3%). The commonest cause of failure of regraft was infection to the corneal graft (recurrence of herpetic infection in 9 eyes and perforated graft ulcers in 3 eyes). Three (18.6%) of the 16 eyes with multiple corneal regrafts achieved a BCVA of 6/60. Overall, only five eyes (all with single regraft) achieved a BCVA of 6/18 or better at the end of follow-up. CONCLUSION: Graft infection is the leading cause of failure of repeat keratoplasty in this part of the world. Prognosis for visual recovery and graft survival is worse in eyes undergoing multiple regrafts

    Matrix metalloproteinases and their tissue inhibitors after selective laser trabeculoplasty in pseudoexfoliative secondary glaucoma

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    <p>Abstract</p> <p>Background</p> <p>The aim of this study was to assess changes in metalloproteinases (MMP-2) and tissue inhibitor of metalloproteinases (TIMP-2) following selective laser trabeculoplasty (SLT) in patients with pseudoexfoliative glaucoma (PEXG).</p> <p>Methods</p> <p>We enrolled 15 patients with PEXG and cataracts (PEXG-C group) and good intraocular pressure (IOP) controlled with β-blockers and dorzolamide eye drops who were treated by cataract phacoemulsification and 15 patients with pseudoexfoliative glaucoma (PEXG-SLT group). The PEXG-SLT patients underwent a trabeculectomy for uncontrolled IOP in the eye that showed increased IOP despite the maximum drug treatment with β-blockers and dorzolamide eye drops and after ineffective selective laser trabeculoplasty (SLT). The control group consisted of 15 subjects with cataracts. Aqueous humor was aspirated during surgery from patients with PEXG-C, PEXG-SLT and from matched control patients with cataracts during cataract surgery or trabeculectomy. The concentrations of MMP-2 and TIMP-2 in the aqueous humor were assessed with commercially available ELISA kits.</p> <p>Results</p> <p>In PEXG-SLT group in the first 10 days after SLT treatment a significant reduction in IOP was observed: 25.8 ± 1.9 vs 18.1.0 ± 1.4 mm/Hg (p < 0.001), but after a mean time of 31.5 ± 7.6 days IOP increased and returned to pretreatment levels: 25.4 ± 1.6 mm/Hg (p < 0.591). Therefore a trabeculectomy was considered necessary.</p> <p>The MMP-2 in PEXG-C was 57.77 ± 9.25 μg/ml and in PEXG-SLT was 58.52 ± 9.66 μg/ml (p < 0.066). TIMP-2 was 105.19 ± 28.53 μg/ml in PEXG-C and 105.96 ± 27.65 μg/ml in PEXG-SLT (p < 0.202). The MMP-2/TIMP-2 ratio in the normal subjects was 1.11 ± 0.44. This ratio increase to 1.88 ± 0.65 in PEXG-C (p < 0.001) and to 1.87 ± 0.64 in PEXG-SLT (p < 0.001). There was no statistically significant difference between the PEXG-C and PEXG-SLT ratios (p < 0.671).</p> <p>Conclusion</p> <p>This case series suggest that IOP elevation after SLT can be a serious adverse event in some PEXG patients. The IOP increase in these cases would be correlated to the failure to decrease the TIMP-2/MMP-2 ratio.</p> <p>Trial registration</p> <p>Current Controlled Trials <b>ISRCTN79745214</b></p

    Trabecular Meshwork Gene Expression after Selective Laser Trabeculoplasty

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    BACKGROUND: Trabecular meshwork and Schlemm's canal are the tissues appointed to modulate the aqueous humour outflow from the anterior chamber. The impairment of their functions drives to an intraocular pressure increase. The selective laser trabeculoplasty is a laser therapy of the trabecular meshwork able to decrease intraocular pressure. The exact response mechanism to this treatment has not been clearly delineated yet. The herein presented study is aimed at studying the gene expression changes induced in trabecular meshwork cells by selective laser trabeculoplasty (SLT) in order to better understand the mechanisms subtending its efficacy. METHODOLOGY/PRINCIPAL FINDINGS: Primary human trabecular meshwork cells cultured in fibroblast medium underwent selective laser trabeculoplasty treatment. RNA was extracted from a pool of cells 30 minutes after treatment while the remaining cells were further cultured and RNA was extracted respectively 2 and 6 hours after treatment. Control cells stored in incubator in absence of SLT treatment were used as reference samples. Gene expression was evaluated by hybridization on miRNA-microarray and laser scanner analysis. Scanning electron microscopic examination was performed on 2 Trabecular meshwork samples after SLT at 4(th) and 6(th) hour from treatment. On the whole, selective laser trabeculoplasty modulates in trabecular meshwork the expression of genes involved in cell motility, intercellular connections, extracellular matrix production, protein repair, DNA repair, membrane repair, reactive oxygen species production, glutamate toxicity, antioxidant activities, and inflammation. CONCLUSIONS/SIGNIFICANCE: SLT did not induce any phenotypic alteration in TM samples. TM is a complex tissue possessing a great variety of function pivotal for the active regulation of aqueous humour outflow from the anterior chamber. SLT is able to modulate these functions at the postgenomic molecular level without inducing damage either at molecular or phenotypic levels

    Mind the (treatment) gap: a global perspective on current and future strategies for prevention of fragility fractures

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    This narrative review considers the key challenges facing healthcare professionals and policymakers responsible for providing care to populations in relation to bone health. These challenges broadly fall into four distinct themes: (1) case finding and management of individuals at high risk of fracture, (2) public awareness of osteoporosis and fragility fractures, (3) reimbursement and health system policy and (4) epidemiology of fracture in the developing world. Findings from cohort studies, randomised controlled trials, systematic reviews and meta-analyses, in addition to current clinical guidelines, position papers and national and international audits, are summarised, with the intention of providing a prioritised approach to delivery of optimal bone health for all. Systematic approaches to case-finding individuals who are at high risk of sustaining fragility fractures are described. These include strategies and models of care intended to improve case finding for individuals who have sustained fragility fractures, those undergoing treatment with medicines which have an adverse effect on bone health and people who have diseases, whereby bone loss and, consequently, fragility fractures are a common comorbidity. Approaches to deliver primary fracture prevention in a clinically effective and cost-effective manner are also explored. Public awareness of osteoporosis is low worldwide. If older people are to be more pro-active in the management of their bone health, that needs to change. Effective disease awareness campaigns have been implemented in some countries but need to be undertaken in many more. A major need exists to improve awareness of the risk that osteoporosis poses to individuals who have initiated treatment, with the intention of improving adherence in the long term. A multisector effort is also required to support patients and their clinicians to have meaningful discussions concerning the risk-benefit ratio of osteoporosis treatment. With regard to prioritisation of fragility fracture prevention in national policy, there is much to be done. In the developing world, robust epidemiological estimates of fracture incidence are required to inform policy development. As the aging of the baby boomer generation is upon us, this review provides a comprehensive analysis of how bone health can be improved worldwide for all
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