The reduction of serum soluble Flt-1 in patients with neovascular age-related macular degeneration

PURPOSE: To evaluate serum soluble Flt-1 (sFlt-1) in age-related degeneration (AMD) patients.

DESIGN: Case control study.

METHODS: Fifty-six non-AMD participants, fifty-three early AMD patients and ninety-seven neovascular AMD patients from Belfast in Northern Ireland. Serum samples were collected from each patient. Serum sFlt-1 was measured by human sVEGFR1/sFlt-1 ELISA kit. The results were analyzed by Excel and SPSS.

RESULTS: Serum sFlt-1 concentration of non-AMD, early AMD, and neovascular AMD were 90.8±2.9 pg/mL (±SEM), 88.2±2.6 pg/mL and 79.9±2.2 pg/mL. sFlt-1 from neovascular AMD patients was significantly decreased compared to non-AMD and early AMD patients (ANOVA, p<0.01). For each 10 point increase in sFlt-1, the odds for having neovascular AMD compared with non-AMD and neovascular AMD decreases by 27.8% OR=0.722 (95% CI: 0.588-0.888, p=0.002) and 27.0% OR=0.730 (95% CI: 0.594-0.898, p=0.003), respectively. In patients over 73 years of age, serum sFlt-1 <80 pg/mL was associated with a >6-fold higher risk of neovascular AMD.

CONCLUSIONS: Reduced serum sFlt-1 differentiates those patients with neovascular AMD from both early AMD and non-AMD participants. In those aged over 73, serum sFlt <80 pg/mL seems to indicate a particularly high risk of neovascular AMD. Our results indicate serum sFlt-1 could be a biomarker for development of neovascular AMD.

Susceptibility to Invasive Meningococcal Disease: Polymorphism of Complement System Genes and Neisseria meningitidis Factor H Binding Protein

BACKGROUND: Neisseria meningitidis can cause severe infection in humans. Polymorphism of Complement Factor H (CFH) is associated with altered risk of invasive meningococcal disease (IMD). We aimed to find whether polymorphism of other complement genes altered risk and whether variation of N. meningitidis factor H binding protein (fHBP) affected the risk association.

METHODS: We undertook a case-control study with 309 European cases and 5,200 1958 Birth Cohort and National Blood Service cohort controls. We used additive model logistic regression, accepting P<0.05 as significant after correction for multiple testing. The effects of fHBP subfamily on the age at infection and severity of disease was tested using the independent samples median test and Student's T test. The effect of CFH polymorphism on the N. meningitidis fHBP subfamily was investigated by logistic regression and Chi squared test.

RESULTS: Rs12085435 A in C8B was associated with odds ratio (OR) of IMD (0.35 [95% CI 0.19-0.67]; P = 0.03 after correction). A CFH haplotype tagged by rs3753396 G was associated with IMD (OR 0.56 [95% CI 0.42-0.76], P = 1.6x10-4). There was no bacterial load (CtrA cycle threshold) difference associated with carriage of this haplotype. Host CFH haplotype and meningococcal fHBP subfamily were not associated. Individuals infected with meningococci expressing subfamily A fHBP were younger than those with subfamily B fHBP meningococci (median 1 vs 2 years; P = 0.025).

DISCUSSION: The protective CFH haplotype alters odds of IMD without affecting bacterial load for affected heterozygotes. CFH haplotype did not affect the likelihood of infecting meningococci having either fHBP subfamily. The association between C8B rs12085435 and IMD requires independent replication. The CFH association is of interest because it is independent of known functional polymorphisms in CFH. As fHBP-containing vaccines are now in use, relationships between CFH polymorphism and vaccine effectiveness and side-effects may become important.

Retinal microvascular network attenuation in Alzheimer's disease

INTRODUCTION:Cerebral small-vessel disease has been implicated in the development of Alzheimer’sdisease (AD). The retinal microvasculature enables non-invasive visualization andevaluation of the systemic microcirculation. We evaluated retinal microvascular parametersin a case-control study of AD patients and cognitively-normal controls. 

METHODS:Retinal images were computationally analyzed and quantitative retinal parameters (caliber,fractal dimension, tortuosity, and bifurcation) measured. Regression models were used tocompute odds ratios (OR) and confidence intervals (CI) for AD with adjustment forconfounders. 

RESULTS:Retinal images were available in 213 AD participants and 294 cognitively-normal controls.Persons with lower venular fractal dimension (OR per standard deviation [SD] increase, 0.77[CI: 0.62–0.97]) and lower arteriolar tortuosity (OR per SD increase, 0.78 [CI: 0.63–0.97])were more likely to have AD following appropriate adjustment. 
DISCUSSION:Patients with AD have a sparser retinal microvascular network and retinal microvascularvariation may represent similar pathophysiological events within the cerebralmicrovasculature of patients with AD.

Thermolabile methylenetetrahydrofolate reductase (C677T):frequency in the Irish population

BACKGROUND: The genetic variation which underlies the thermolability and low enzyme activity of 5,10-methylenetetrahydrofolate reductase (MTHFR; C677T) has been extensively studied in many populations, including the Irish population.

AIM: To describe the examination of the C677T substitution in two new control samples drawn from the Irish population.

METHODS: A collection of 487 serum samples was obtained through the blood transfusion services of both the Republic of Ireland and Northern Ireland and a further 115 samples from volunteers.

RESULTS: In both samples, the frequency of the thermolabile/low enzyme activity allele (T) was higher than that previously reported for the Irish population.

CONCLUSION: This finding thus supports the need for a greater use of internal control/family-based association studies, as opposed to the classic case control study design, when assessing the contribution of the MTHFR T allele to disease processes.

The common vaginal commensal bacterium Ureaplasma parvum is associated with chorioamnionitis in extreme preterm labour

OBJECTIVE: To assess the association of vaginal commensal and low grade pathogenic bacteria including Ureaplasma parvum, Ureaplasma urealyticum, Mycoplasma hominis, Mycoplasma genitalium, Group B Streptococcus (GBS), and Gardnerella vaginalis, in women who delivered preterm at less than 37 weeks gestation in the presence or absence of inflammation of the chorioamnionitic membranes.

METHODS: A case control study involving women who delivered before 37 weeks gestation with and without inflammation of chorioamnionitic membranes. A total of 57 placental samples were histologically examined for polymorphonuclear leukocyte infiltration of placental tissue for evidence of chorioamnionitis, and by type-specific nucleic acid amplification for evidence of infection with one or more of the target bacteria. Demographic data was collected for each mother.

RESULTS: Amongst the 57 placental samples, 42.1% had chorioamnionitis and 24.6% delivered in the second trimester of pregnancy; U. parvum, U. urealyticum, G. vaginalis and GBS were all detected in the study with respective prevalence of 19.3%, 3.5%, 17.5% and 15.8%; M.genitalium and M. hominis were not detected. U. parvum was significantly associated with chorioamnionitis (p value = 0.02; OR 5.0; (95% CI 1.2-21.5) and was more common in women who delivered in the second (35.7%) compared to the third trimester of pregnancy (13.9%). None of the other bacteria were associated with chorioamnionitis or earlier delivery and all G.vaginalis positive women delivered in the third trimester of pregnancy (p value 0.04).

CONCLUSIONS: The detection of U. parvum in placental tissue was significantly associated with acute chorioamnionitis in women presenting in extreme preterm labour.

Validation of night blindness reports among children and women in a vitamin A deficient population in rural Tanzania.

OBJECTIVE: This study validates different definitions of reported night blindness (XN) in a vitamin A deficient African population with no local term for XN. DESIGN: Case-control study with follow-up after treatment. SETTING: Eight primary schools and health centres in rural Tanzania. SUBJECTS: A total of 1214 participants were screened for reported XN and other eye signs of xerophthalmia: 461 children aged 24-71 months, 562 primary school-age children and 191 pregnant or breast-feeding women. All 152 cases of reported XN were selected for the validation study and group matched with 321 controls who did not complain of XN. XN reports were validated against serum retinol concentrations and pupillary dark adaptation measurements in cases and controls. INTERVENTION: All children and women who reported XN or had other signs of active xerophthalmia were treated with vitamin A and followed up 3-4 weeks later. Half of the untreated control group who had their serum retinol examined in the baseline examination were also followed up. RESULTS: The overall prevalence of reported XN was 12.5%. At baseline, mean pupillary threshold (-1.52 vs -1.55 log cd/m(2), P=0.501) and median serum retinol concentrations (0.95 vs 0.93 micromol/l, P=0.734) were not significantly different in cases and controls either overall or in each population group. More restricted case definitions reduced the prevalence of reported XN to 5.5% (P<0.001), but there was still no significant difference between cases and controls although the results were in the expected direction. After treatment, the median serum retinol concentration improved significantly only in the most deficient group, the young children. Dark adaptation improved in all the subgroups but the difference was only significant for young children and primary school-age children when the restricted case definitions were used. CONCLUSIONS: XN reports are a poor indicator of vitamin A deficiency in this population. SPONSORSHIP: Task Force Sight and Life, Basel, Switzerland.

Reduced risk of pancreatic cancer associated with asthma and nasal allergies

OBJECTIVE: Studies indicate an inverse association between ductal adenocarcinoma of the pancreas (PDAC) and nasal allergies. However, controversial findings are reported for the association with asthma. Understanding PDAC risk factors will help us to implement appropriate strategies to prevent, treat and diagnose this cancer. This study assessed and characterised the association between PDAC and asthma and corroborated existing reports regarding the association between allergies and PDAC risk.

DESIGN: Information about asthma and allergies was collated from 1297 PDAC cases and 1024 controls included in the PanGenEU case-control study. Associations between PDAC and atopic diseases were studied using multilevel logistic regression analysis. Meta-analyses of association studies on these diseases and PDAC risk were performed applying random-effects model.

RESULTS: Asthma was associated with lower risk of PDAC (OR 0.64, 95% CI 0.47 to 0.88), particularly long-standing asthma (>=17 years, OR 0.39, 95% CI 0.24 to 0.65). Meta-analysis of 10 case-control studies sustained our results (metaOR 0.73, 95% CI 0.59 to 0.89). Nasal allergies and related symptoms were associated with lower risk of PDAC (OR 0.66, 95% CI 0.52 to 0.83 and OR 0.59, 95% CI 0.46 to 0.77, respectively). These results were supported by a meta-analysis of nasal allergy studies (metaOR 0.6, 95% CI 0.5 to 0.72). Skin allergies were not associated with PDAC risk.

CONCLUSIONS: This study shows a consistent inverse association between PDAC and asthma and nasal allergies, supporting the notion that atopic diseases are associated with reduced cancer risk. These results point to the involvement of immune and/or inflammatory factors that may either foster or restrain pancreas carcinogenesis warranting further research to understand the molecular mechanisms driving this association.

Modifiable lifestyle factors associated with risk of sessile serrated polyps, conventional adenomas, and hyperplastic polyps

Objective: To identify modifiable factors associated with sessile serrated polyps (SSPs), and compare the association of these factors to conventional adenomas (ADs) and hyperplastic polyps (HPs). Design: We utilized data from the Tennessee Colorectal Polyp Study, a colonoscopy-based case-control study. Included were 214 SSP cases, 1779 AD cases, 560 HP cases and 3851 polyp-free controls. Results: Cigarette smoking was associated with increased risk for all polyps and was stronger for SSPs than for ADs (OR 1.74. 95% CI: 1.16-2.62, for current vs. never, ptrend=0.008). Current regular use of nonsteroidal anti-inflammatories (NSAID) was associated with a 40% reduction in SSPs risk in comparison to never-users (OR 0.68, 95% CI 0.48-0.96, ptrend=0.03), similar to the association with AD. Red meat intake was strongly associated with SSPs risk (OR 2.59, 95% CI 1.41-4.74 for highest vs. lowest intake, ptrend<0.001) and the association with SSP was stronger than with AD (ptrend=0.003). Obesity, folate intake, fiber intake, and fat intake were not associated with SSP risk after adjustment for other factors. Exercise, alcohol use, and calcium intake were not associated with risk for SSPs. Conclusion: SSPs share some modifiable risk factors for ADs, some of which are more strongly associated with SSPs than ADs. Thus, preventive efforts to reduce risk for ADs may also be applicable to SSPs. Additionally, SSPs have some distinctive risk factors. Future studies should evaluate the preventive strategies for these factors. The findings from this study also contribute to an understanding of the etiology and biology of SSPs.