Borderline Significance (borderline + significance)

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Distribution within Medical Sciences

Selected Abstracts

Gene,gene interactions between HNF4A and KCNJ11 in predicting Type 2 diabetes in women

L. Qi
Abstract Aims Recent studies indicate transcription factor hepatocyte nuclear factor 4, (HNF-4,, HNF4A) modulates the transcription of the pancreatic B-cell ATP-sensitive K+ (KATP) channel subunit Kir6.2 gene (KCNJ11). Both HNF4A and KCNJ11 have previously been associated with diabetes risk but little is known whether the variations in these genes interact with each other. Methods We conducted a prospective, nested case,control study of 714 incident cases of Type 2 diabetes and 1120 control subjects from the Nurses' Health Study. Results KCNJ11 E23K was significantly associated with an increased diabetes risk (odds ratio 1.26, 95% CI 1.03,1.53) while HNF4A P2 promoter polymorphisms were associated with a moderately increased risk at borderline significance. By using a logistic regression model, we found significant interactions between HNF4A rs2144908, rs4810424 and rs1884613 and KCNJ11 E23K (P for interaction = 0.017, 0.012 and 0.004, respectively). Carrying the minor alleles of the three HNF4A polymorphisms was associated with significantly greater diabetes risk in women carrying the KCNJ11 allele 23K, but not in those who did not carry this allele. Analyses using the multifactor dimensionality reduction (MDR) method confirmed the gene,gene interaction. We identified that the best interaction model included HNF4A rs2144908 and KCNJ11 E23K. Such a two-locus model showed the maximum cross-validation consistency of 10 out of 10 and a significant prediction accuracy of 54.2% (P = 0.01) on the basis of 1000-fold permutation testing. Conclusions Our data indicate that HNF4A P2 promoter polymorphisms may interact with KCNJ11 E23K in predicting Type 2 diabetes in women. [source]

The Effect of Hemodialysis on Left Ventricular Outflow Tract Gradient

Pawel Petkow Dimitrow M.D.
Background: The aim of the study was to assess the effect of hemodialysis (HD) on left ventricular outflow tract gradient (LVOTG) measured both in supine and upright position (provocative maneuver to unload LV cavity by rapid preload reduction). Supine/standing echocardiography was performed immediately before and immediately after HD. For additional verification of the hypothesis about preload-dependence of LVOTG, the echocardiograms after long (2-day delay HD due to weekend) versus short (usual 1-day) pause between HDs were compared. Methods: Forty-one patients on chronic HD (mean age 44 ± 11 years) were examined using a portable hand-carried echocardiograph. In accordance with the prestudy assumption the ultrafiltration volume was significantly greater during HD after a long pause in comparison to HD after a short pause (3707 ± 2826 mL vs. 2665 ± 1152 mL P < 0.05). Results: After a long pause, the mean value of LVOTG at the pre-HD was mildly increased in the supine position and remained at a similar level in the upright position (13.1 ± 6.1 vs. 13.6 ± 9.1 mmHg). Mean LVOTG at the post-HD in the supine position was similar to pre-HD, however the orthostatic stress test induced a significant increase of LVOTG (13.9 ± 15.2 vs. 18.2 ± 19.9 mmHg P < 0.05). After a short pause at the pre-HD the LVOTG in the supine position and after the orthostatic provocation was very similar to measurements after long pause (13.3 ± 9.1 vs. 13.3 ± 10.8 mmHg). At the post-HD the mean value of LVOTG increased during upright posture but the differences were of borderline significance (13.2 ± 6.6 vs. 17.9 ± 18.6 mmHg P = 0.052). Conclusions: HD predisposed to standing-provoked LVOTG especially when a long pause (2 days) between HDs induced a greater weight gain and subsequently a larger volume of ultrafiltration was needed to reduce hypervolemia. (Echocardiography 2010;27:603-607) [source]

Association between tobacco control policies and smoking behaviour among adolescents in 29 European countries

ADDICTION, Issue 11 2009
Anne Hublet
ABSTRACT Aims To investigate the associations between well-known, cost-effective tobacco control policies at country level and smoking prevalence among 15-year-old adolescents. Design Multi-level modelling based on the 2005,06 Health Behaviour in School-aged Children Study, a cross-national study at individual level, and with country-level variables from the Tobacco Control Scale and published country-level databases. Setting Twenty-nine European countries. Participants A total of 25 599 boys and 26 509 girls. Main outcome measures Self-reported regular smoking defined as at least weekly smoking, including daily smoking (dichotomous). Findings Interaction effects between gender and smoking policies were identified, therefore boys and girls were analysed separately. Large cross-national differences in smoking prevalence were documented. Intraclass correlations (ICC) of 0.038 (boys) and 0.035 (girls) were found. In the final multi-level model for boys, besides the significance of the individual variables such as family affluence, country-level affluence and the legality of vending machines were related significantly to regular smoking [b(country affluence) = ,0.010; b(partial restriction vending machines) = ,0.366, P < 0.05]. Price policy was of borderline significance [b(price policy) = ,0.026, P = 0.050]. All relationships were in the expected direction. The model fit is not as good for girls; only the legality of vending machines had a borderline significance in the final model [b(total ban vending machines) = ,0.372, P = 0.06]. Conclusions For boys, some of the currently recommended tobacco control policies may help to reduce smoking prevalence. However, the model is less suitable for girls, indicating gender differences in the potential efficacy of smoking policies. Future research should address this issue. [source]

Varenicline in prevention of relapse to smoking: effect of quit pattern on response to extended treatment

ADDICTION, Issue 9 2009
Peter Hajek
ABSTRACT Aim While older behavioural and pharmacological approaches to preventing relapse to smoking show little efficacy, a recent randomized trial of an extended course of varenicline reported positive results. In this secondary analysis, trial data were examined to see whether smokers who manage to achieve abstinence only later in the original course of treatment are more likely to benefit from having the course extended. Methods A total of 1208 patients abstinent for at least the last week of 12 weeks' treatment with varenicline were randomized to 3 months continued varenicline or placebo. Overall, 44% of the 12-week abstainers were abstinent from the target quit date (TQD), while the rest stopped smoking later. We examined the relationship between quit pattern and the varenicline versus placebo difference in continuous abstinence rates at week 52 and contributions of baseline patient characteristics. Results With increasing delay in initial quitting, 12-month success rates declined. Participants who had their last cigarette at week 11 of open-label treatment had quit rates at 52 weeks of 5.7% compared with 54.9% in those who last smoked in week 1 [odds ratio (OR) 20.3 (6.3, 65.9); P < 0.0001]. Patients who failed to initiate abstinence in the first week benefited more from extended treatment than patients continuously abstinent from week 1 [OR 1.7 (1.2, 2.4); P = 0.0015 versus OR 1.1 (0.8, 1.5); P = 0.6995, respectively; with the interaction of the quit pattern with treatment effect reaching borderline significance (P = 0.0494)]. No other patient characteristics were related to treatment effect. Conclusions Compared with smokers who quit smoking on their TQD, those who have an initial delay in achieving sustained abstinence have increased risk of relapse even several months later, and may be more likely to benefit from extended treatment with varenicline. [source]

Survey of major chronic iIlnesses and hospital admissions via the emergency department in a randomized older population in Randwick, Australia

Daniel KY Chan
Abstract Objective: To find out if patients with chronic illnesses living in the community are at risk of unplanned hospital admissions through emergency departments; what types of chronic illnesses may be putative risk factors; and if an increase in the number of chronic illnesses may be associated with increased risk. Methods: The survey included the completion of a standardized questionnaire for medical illnesses in a random sample of older people dwelling in the community and analysis of admission records to our hospital. The principal diagnoses for admissions were recorded. The risk factors for admissions were analysed. Results: Five hundred and twenty-six (239 men and 287 women) people aged 55 years and over were interviewed. Musculoskeletal disorders, hypertension, gastrointestinal disorders and ischaemic heart disease were the most frequently reported of the chronic illnesses surveyed. A total number of 70 people from the survey group with a total of 115 admissions through emergency departments were recorded. Using logistic regression model, hypertension, ischaemic heart disease and age were found to be risk factors for emergency admissions amongst this group of community-dwelling residents. The ratios were 2.03 (95% confidence interval (CI): 1.2,3.44), 2.02 (95% CI: 1.16,3.49) and 1.05 (95% CI: 1.02,1.09), respectively. Furthermore, multiple (three or more) chronic illnesses were found to be a strong predictor of hospital admission via emergency department (chi-square = 16.647, DF = 1, P -value < 0.001). Conclusion: We conclude that there was significant association between multiple chronic diseases and emergency admissions for older people. Of these, hypertension and ischaemic heart disease were found to be significant predictors. Age per se was found to be of borderline significance. [source]

Mixed cryoglobulinemia is associated with increased risk for death, or neoplasia in HIV-1 infection

T. Kordossis
Backround Cryoglobulinemia has been reported in several chronic infectious and autoimmune diseases, and in patients with HIV-1 infection. Cryoglobulinemia associated with hepatitis C virus infection is considered a risk factor for the development of neoplasia, especially B-cell non-Hodgkin lymphoma. This study was undertaken to investigate whether the presence of circulating cryoglobulins is associated with survival or development of neoplastic disease in HIV-1 infection. Design We evaluated 87 unselected consecutive HIV-1 infected patients for the presence of cryoglobulinemia and they were prospectively followed up for a median of 34 months, with clinic visits at 4-month intervals. None of the patients had neoplasia at study entry. Time-to-event analysis for death, neoplasm and B-cell lymphoproliferative disorder were performed with Cox proportional hazards models. Results Mixed cryoglobulinemia (types II and III) was detected in 24 (28%) of the 87 patients. During the follow up, 12 patients died and 8 developed neoplastic disease. Multivariate analysis showed that circulating cryoglobulins were an independent predictor of death [relative risk (RR), 4·97; 95% confidence intervals (CI), 1·26,19·63] and development of neoplasia (RR, 5·18; 95% CI, 1·23,21·83). In addition, cryoglobulinemia reached borderline significance as a predictor of lymphoproliferative disorder of B-cell origin (P = 0·08; RR, 4·53; 95% CI, 0·83,24·75). Conclusions Our results suggest that cryoglobulinemia is associated with an increased risk for death, neoplasia or development of lymphoproliferative disorder of B-cell origin, in HIV-1 infected patients. [source]

CLLU1 expression levels predict time to initiation of therapy and overall survival in chronic lymphocytic leukemia

Anne Mette Buhl
Abstract:,Objectives:,Chronic lymphocytic leukemia (CLL) is an incurable disease with a highly variable clinical course. IgVH mutational status, chromosomal aberrations, CD38 expression and ZAP-70 expression are prognostic markers in CLL, however, they are not exclusively confined to this disease. We recently identified a novel CLL-specific gene (CLL upregulated gene1, CLLU1) that is exclusively upregulated in CLL cells. Here we describe our evaluation of the prognostic significance of CLLU1 in CLL. Methods:,A cohort of 59 previously untreated CLL patients was studied. We determined the expression levels of two CLLU1 transcripts, cDNA1 and CDS, by quantitative RT-PCR. The relation between CLLU1 expression and time to therapy, overall survival and presence or absence of ZAP-70, CD38, chromosomal aberrations or IgVH mutations in the 59 patients was analyzed. Results:,Analyzed as a continuous, quantitative parameter CLLU1 levels significantly predicted time from diagnosis to initiation of therapy (P , 0.0003) Analyzed as a categorical parameter, by segregation of the patients into groups with cDNA1 or CDS expression above or below the median, the CLLU1 levels significantly predicted time from diagnosis to initiation of therapy (P = 0.001) and predicted overall survival with borderline significance (P , 0.05). Patient stratification according to clinical stage, cytogenetics, IgVH mutational status, ZAP-70 and CD38, demonstrated significantly increased CLLU1 expression in all investigated CLL poor risk groups. CLLU1 expression levels contributed additional prognostic information to ZAP-70-positive patients. Conclusions:,CLLU1 is the first identified CLL specific gene. The CLLU1 mRNA expression level can predict time to initiation of treatment and survival in CLL patients. [source]

Carriage of a tumor necrosis factor polymorphism amplifies the cytotoxic T-lymphocyte antigen 4 attributed risk of primary biliary cirrhosis: Evidence for a gene,gene interaction,

HEPATOLOGY, Issue 1 2010
Brian D. Juran
Common genetic variants significantly influence complex diseases such as primary biliary cirrhosis (PBC). We recently reported an association between PBC and a single nucleotide polymorphism (rs231725) of the immunoreceptor gene cytotoxic T-lymphocyte antigen 4 (CTLA4). We hypothesized that PBC risk attributed to this polymorphism might be increased by propensity to an overly robust inflammatory response. Thus, we examined its potential interaction with the commonly studied ,308AG promoter polymorphism (rs1800629) of the tumor necrosis factor (TNF) gene for which the variant TNF2A allele causes increased TNF production. The polymorphisms were genotyped in 866 PBC patients and 761 controls from independent US and Canadian registries; the effects of individual single nucleotide polymorphisms (SNPs) and their interaction on PBC risk was assessed by logistic regression. The reported association of PBC with the CTLA4 "A/A" genotype was replicated in the Canadian cohort and significant for PBC risk in the combined data (odds ratio [OR], 1.68; P = 0.0005). TNF2A allele frequency was elevated in PBC patients, but only reached borderline significance using the combined data (OR, 1.21; P = 0.042). Analysis showed that TNF2A carriage was significantly increased in CTLA4 "A/A" PBC patients compared with CTLA4 "A/A" controls (39.7% versus 16.5%, P = 0.0004); no apparent increase of TNF2A carriage was noted in CTLA4 "A/G" or "G/G" individuals. Finally, interaction under a logistic model was highly significant, as TNF2A carriage in combination with the CTLA4 "A/A" genotype was present in 6.5% of PBC patients, compared with 1.7% of controls (OR, 3.98; P < 0.0001). Conclusion: TNF2A amplifies the CTLA4 rs231725 "A/A" genotype risk for PBC. Although the mechanisms remain unclear, the premise that deficiency in T-cell regulation resulting in an increased risk of PBC is amplified by overexpression of an important proinflammatory cytokine provides a basis for future functional studies. HEPATOLOGY 2010 [source]

Micronutrients and the risk of renal cell cancer: A case-control study from Italy

Cristina Bosetti
Abstract The role of various micronutrients on the risk of renal cell cancer (RCC) was examined in a multicentric case-control study from Italy, in which information on dietary habits were collected using a validated food-frequency questionnaire. Cases were 767 patients (494 men and 273 women) with incident, histologically confirmed RCC; controls were 1,534 subjects (988 men and 546 women) admitted to the same hospitals as cases for a wide spectrum of acute, nonneoplastic conditions. After allowing for energy and other major covariates, a significant inverse association was found for vitamin E (odds ratio, OR, for the highest quintile of intake versus the lowest one 0.56, 95% confidence interval, CI 0.41,0.75), and vitamin C (OR = 0.72, 95% CI = 0.54,0.96), although the trend in risk for vitamin C was of borderline significance. No significant trend of decreasing risk was found for other micronutrients analyzed, although for most of them the risk estimates were below unity for intakes above the lowest. The ORs for the upper quintile of intake when compared with the lowest one were 0.80 (95% confidence interval, CI = 0.59,1.08) for retinol, 0.82 (95% CI = 0.61,1.10) for ,-carotene, 0.90 (95% CI = 0.68,1.20) for ,-carotene, 0.94 (95% CI = 0.73,1.21) for ,-criptoxanthin, 0.85 (95% CI = 0.63,1.14) for lutein/zeaxanthin, 0.76 (95% CI = 0.57,1.01) for vitamin D, 0.75 (95% CI = 0.55,1.01) for thiamine, 0.88 (95% CI = 0.66,1.19) for riboflavin, 0.85 for vitamin B6 (95% CI = 0.64,1.13), 0.85 (95% CI = 0.64,1.12) for folate and 0.80 (95% CI = 0.60,1.07) for niacin. No meaningful associations emerged for lycopene (OR = 1.11). The present findings support a possible beneficial effect of vitamin E and C on RCC. © 2006 Wiley-Liss, Inc. [source]

Alteration of subcellular and cellular expression patterns of cyclin B1 in renal cell carcinoma is significantly related to clinical progression and survival of patients

Stephen O. Ikuerowo
Abstract Cyclin B1, identified as a regulator of late cell cycle, is involved in the development and progression of a variety of human malignancies. To clarify the role of cyclin B1 in the pathogenesis and prognosis of renal cell carcinoma (RCC), protein expression was compared with clinicopathological characteristics of patients as well as the long-term survival after surgical therapy. Expression analysis was carried out by immunohistochemistry and tissue microarray analysis. The microarrays that represented the primary tumors, their invasion front and normal peritumoral renal parenchyma contained 753 tissue cores obtained from 251 randomly selected nephrectomy specimens. Immunopositivity within the primary tumors was significantly associated with tumor stage (pT) (p < 0.01), lymph node status (pN) (p < 0.01) as well as the presence of systemic metastatic disease (p = 0.01). Subcellular expression in the cytoplasm of tumor cells significantly correlated with pT (p = 0.02) and pN (p = 0.03). When peritumoral tissue samples exhibited a relative amount of <10% of positively reacting epithelial cells, cyclin B positivity was identified to predict long-term survival of patients in univariate analysis (p < 0.01) whereas borderline significance was observed in multivariate statistical analysis (p = 0.05). Increased intratumoral cyclin B1 positivity and aberrant localization of signals within the cytoplasm of tumor cells is positively correlated with the tendency towards tumor progression, indicating the significant role of cyclin B1 in the development and pathogenesis of RCC. The result of uni- and multivariate statistical analysis suggests the prognostic value of cyclin B1 for RCC patients. © 2006 Wiley-Liss, Inc. [source]

High ,-fetoprotein level correlates with high stage, early recurrence and poor prognosis of hepatocellular carcinoma: Significance of hepatitis virus infection, age, p53 and ,-catenin mutations

Shian-Yang Peng
Abstract ,-Fetoprotein (AFP) is often elevated in hepatocellular carcinoma (HCC). This study was to elucidate the significance and related factors of AFP elevation in HCC in 781 unifocal HCCs receiving curative hepatectomy. We showed that high AFP (> 200 ng/ml), which was associated with AFP mRNA expression in HCC (p = 0.00001), correlated with major clinicopathologic factors. Younger age (, 55 years; p = 0.00001), hepatitis B surface antigen (HBsAg) in serum (p = 0.00001), p53 mutation (p = 0.008), large tumor (p = 0.00001), vascular invasion (p = 0.00001) and early tumor recurrence (p = 0.00001) were significant associates of high AFP, while anti-HCV in serum and ,- catenin mutation in HCC had less frequent high AFP (p = 0.013 and < 0.0001, respectively). We also showed that HCC with high AFP had a lower 10-year survival (p < 0.0001), particularly in large HCC (p < 0.0001). At univariate analysis, high AFP (p < 0.0001), HBsAg positivity (p = 0.05), p53 mutation (p = 0.0004), liver cirrhosis (p = 0.0094), large tumor (p = 0.0003), vascular invasion (p < 0.0001) and early recurrence (p < 0.0001) were significant unfavorable prognostic factors. In Cox proportional hazards regression analysis, high AFP remained a borderline significance (OR = 1.2; CI = 1.0,1.4) after adjustment for the effect of tumor size and tumor stage (p = 0.0821). Furthermore, the detection of AFP mRNA in the liver of AFP mRNA-positive HCC was associated with more frequent early recurrence (p = 0.0026) and might be a useful marker of intrahepatic spread. We therefore conclude that AFP elevation, more than a coincidental epiphenomenon, appears to contribute to vascular invasion and HCC progression and help to identify subsets of HCC patients with increased risk for early recurrence and poor prognosis after hepatectomy. © 2004 Wiley-Liss, Inc. [source]

Preoperative hCG, and CA 72-4 are prognostic factors in gastric cancer

Johanna Louhimo
Abstract In gastric cancer, the role of tumour markers in assessment of prognosis is unconfirmed. In our study, we evaluated the prognostic significance of serum tumour markers carcinoembryonic antigen (CEA), CA 19-9, CA 72-4, CA 242 and free , subunit of human chorionic gonadotropin (hCG,) in gastric cancer. Preoperative serum samples were obtained from 146 patients with gastric cancer, including 29 with stage I, 11 with stage II, 42 with stage III and 64 patients with stage IV cancer. Quantitation of CEA, CA 19-9, CA 72-4 and CA 242 in serum was performed with commercial assays. HCG, was measured with an in-house immunofluorometric assay based on monoclonal antibodies specific for the free ,-subunit of hCG. Survival analysis was performed with Kaplan-Meier life-tables and log-rank test, and with multivariate Cox regression analysis. Disease-specific cumulative 2-year survival rate was 40%. Serum levels of CEA, CA 72-4, CA 242 and hCG, showed significant correlation with stage (p<0.027); for CA 19-9 the association was of borderline significance (p=0.056). Of the studied markers, CA 19-9, CA 72-4, CA 242 and hCG, were found to be prognostic factors in univariate analysis (p< 0.022). In multivariate analysis, stage had the statistically most significant association with prognosis followed by hCG,, tumour histology according to the Laurén classification and by CA 72-4. In gastric cancer, tumour markers hCG, and CA 72-4 are independent prognostic factors in addition to stage and histological type of the tumour. © 2004 Wiley-Liss, Inc. [source]

Transobturatory tension-free composite sling for urethral support in patients with stress urinary incontinence: Favorable experience after 1 year follow up

Objective:, Symptomatic, anatomic and urodynamic results of a composite transobturatory tension-free sling with an absorbable middle part, in patients with stress urinary incontinence (SUI), were studied. Methods:, A prospective study in 40 women with SUI was performed. Symptoms, urodynamics and anatomical improvements were evaluated separately. Surgery was performed with the transobturatory approach. Results:, All patients had both clinically and urodynamically confirmed SUI. Clinical outcome was favorable in 36/40 (90%) patients, after 1 year. Operation improved the position of the bladder neck (2.8 cm and 1.4 cm below the pubic bone, respectively) and significantly decreased mobility of the bladder neck during abdominal straining (3.3 cm and 1.7 cm, respectively). Both symptoms and quality of life were significantly improved 1 month after the surgery. Postoperative maximum flow was lower than the preoperative one but with borderline significance (25.8 and 23.7 mL/s; P = 0.05). Pressure flow study showed unobstructed voiding both preoperatively and postoperatively. Detrusor pressure at the maximum flow was increased (20, 4 and 22, 8 cmH2O, respectively) but not significantly. Conclusion:, Our results confirmed a high objective cure rate, improvement of symptoms and quality of life, and at the same time, corrected position of the bladder neck and unobstructed voiding. [source]

The Effect of Changing Practice on Fall Prevention in a Rehabilitative Hospital: The Hospital Injury Prevention Study

Michael Vassallo FRCP
Objectives: To determine whether a change in practice to introduce a multidisciplinary fall-prevention program can reduce falls and injury in nonacute patients in a rehabilitation hospital. Design: A quasi-experimental study. Setting: Three geriatric wards with a similar design, equipment, staffing levels, and skill mix. Participants: Eight hundred twenty-five consecutive patients. Intervention: The patients' fall-risk status was assessed using the Downton Score. Current practice was maintained on the two control wards (n=550). On the experimental ward (n=275), a fall-prevention program was introduced. A multidisciplinary team met weekly specifically to discuss patients' fall risk and formulate a targeted plan. Patients at risk were identified using wristbands; risk factors were corrected or environmental changes made to enhance safety. Measurements: Primary outcomes were number of fallers, recurrent fallers, total falls, patients sustaining injury, and falls per occupied bed days. Secondary outcomes were place of discharge and mortality. Results: Patients were matched for age and risk status. Control wards had proportionally more fallers (20.2% vs 14.2%: P=.033), patients sustaining injury (8.2% vs 4%: P=.025), and total number of falls (170 vs 72: P=.045). These results did not remain significant after controlling for differing length of stay. There was no reduction in recurrent fallers (6.4% vs 4.7%: P=.43) and no effect on place of discharge (home discharges; 57.5% vs 60.7%: P=.41) or mortality (15.3% vs 13.8%: P=.60). Conclusion: This study shows that falls might be reduced in a multidisciplinary fall-prevention program, but the results are not definitive because of the borderline significance achieved and the variable length of stay. More research on fall prevention in hospital is required, particularly as to what interventions, if any, are effective at reducing falls in this group of patients. [source]

Reduced oxidative stress in parallel to improved cardiac performance one year after selective removal of anti-beta 1-adrenoreceptor autoantibodies in patients with idiopathic dilated cardiomyopathy: data of a preliminary study,

Ingolf Schimke
Abstract Patients with idiopathic dilated cardiomyopathy (IDC) were treated with selective immunoadsorption to remove anti-beta 1-adrenoreceptor autoantibodies (anti-beta1A-AB). After one year, the effect on cardiac performance and oxidative stress was tested. Extracorporeal immunoadsorption of the whole IgG class in IDC patients for the removal of anti-beta1A-AB reduced oxidative stress in parallel to an improvement of cardiac performance. However, the non-specificity of IgG adsorption means that these beneficial effects cannot be attributed exclusively to anti-beta1A-AB removal. In an open clinical pilot study enrolling 8 patients with IDC prior to and one year after selective immunoadsorption of anti-beta1A-AB, plasma markers for oxidative stress,thiobarbituric acid-reactive substances (TBARS), lipid peroxides (LPO) and anti-oxidized low-density lipoprotein autoantibodies (anti-oxLDL-AB),were measured in parallel to evaluation of the left ventricular function using conventional echocardiography and wall motion analysis by tissue Doppler imaging. After one year, TBARS (Wilcoxon test with bootstrapping simulation for paired data: 95% confidence interval of the P value 0.020 to 0.029) and anti-oxLDL-AB (P = 0.025 to 0.035) were decreased in parallel to an improvement of the peak systolic wall motion velocity (P = 0.006 to 0.01) and left ventricular ejection fraction (P = 0.002 to 0.02). For changes over the study period, a direct correlation with borderline significance (P = 0.076) was calculated for TBARS to the left ventricular diameter in the diastole. One year after selective immunoadsorption for anti-beta1A-AB removal, patients with ICD show a reduction in oxidative stress and a parallel improvement in cardiac performance. J. Clin. Apheresis © 2005 Wiley-Liss, Inc. [source]

Effect of slice thickness on liver lesion detection and characterisation by multidetector CT

JT Smith
Summary The purpose of our study was to compare the effectiveness of 3.2 mm, 5 mm and 7.5 mm slice thicknesses in the detection and characterisation of liver lesions found on CT in patients with known or suspected malignant disease. 110 patients underwent portal phase imaging using four-slice MDCT. Two blinded observers independently read hard copy images at each slice thickness. The size and location of each lesion detected was recorded by each observer on a diagram of liver segmental anatomy. Each lesion was characterised as benign, malignant or indeterminate in nature. A diagnostic confidence score was allocated for each lesion on a scale of 1,4. The pathology or behaviour of lesions was assessed using surgery with intra-operative ultrasound (IOUS) and histology, or interval imaging with MRI, CT, or sonography. 294 lesions were detected, 64 (22%) of which were malignant. Both observers detected significantly more lesions on the 3.2 mm versus 7.5 mm slice thickness (p < 0.0001). Both observers detected more malignant lesions on 3.2 mm and 5 mm slice thicknesses versus 7.5 mm. As slice thickness decreased there was a significant increase in the sensitivity of malignant lesion detection for observer 1 (p < 0.001) and borderline significance for observer 2 (p = 0.07). As slice thickness decreased the proportion of lesions characterised as indeterminate by both observers fell. With thinner slices, both detection and characterisation of liver lesions were improved. A slice thickness no greater than 5 mm should be used to maximise both detection and correct characterisation of liver lesions. [source]

Invasive breast cancers detected by screening mammography: A detailed comparison of computer-aided detection-assisted single reading and double reading

JN Cawson
Summary To compare double reading plus arbitration for discordance, (currently best practice, (BP)) with computer-aided-detection (CAD)-assisted single reading (CAD-R) for detection of invasive cancers detected within BreastScreen Australia. Secondarily, to examine characteristics of cancers detected/rejected using each method. Mammograms of 157 randomly selected double-read invasive cancers were mixed 1:9 with normal cancers (total 1569), all detected in a BreastScreen service. Cancers were detected by two readers or one reader (C2 and C1 cancers, ratio 70:30%) in the program. The 1569 film-screen mammograms were read by two radiologists (reader A (RA) and reader B(RB)), with findings recorded before and after CAD. Discordant findings with BP were resolved by arbitration. We compared CAD-assisted reading (CAD-RA, CAD-RB) with BP, and CAD and arbitration contribution to findings. We correlated cancer size, sensitivity and mammographic density with detection methods. BP sensitivity 90.4% compared with CAD-RA sensitivity 86.6% (P = 0.12) and CAD-RB 94.3% (P = 0.14). CAD-RB specificity was less than BP (P = 0.01). CAD sensitivity was 93%, but readers rejected most positive CAD prompts. After CAD, reader's sensitivity increased 1.9% and specificity dropped 0.2% and 0.8%. Arbitration decreased specificity 4.7%. Receiving operator curves analysis demonstrated BP accuracy better than CAD-RA, borderline significance (P = 0.07), but not CAD-RB. Secondarily, cancer size was similar for BP and CAD-R. Cancers recalled after arbitration (P = 0.01) and CAD-R (P = 0.10) were smaller. No difference in cancer size or sensitivity between reading methods was found with increasing breast density. CAD-R and BP sensitivity and cancer detection size were not significantly different. CAD-R specificity was significantly lower for one reader. [source]

Thr105Ile, a Functional Polymorphism of Histamine N-Methyltransferase, Is Associated with Alcoholism in Two Independent Populations

ALCOHOLISM, Issue 3 2005
Gabor Oroszi
Background: Histamine is expressed in cortical and limbic areas that are involved in emotion and cognition and modulates these behaviors. H1 receptor antagonists are sedative. Histamine N-methyltransferase (HNMT) catalyzes the N, methylation of histamine, the sole pathway for termination of the neurotransmitter action of histamine in mammalian brain. A common and functionally significant polymorphism, a C314T transition in exon 4 of the HNMT gene results in a Thr105Ile substitution of the protein encoded. The Thr105 allele is associated with ,2-fold higher enzyme activity, leading to the prediction that it might be associated with diminished histamine levels, resulting in differences in anxiety, cognition, and sedation that play important roles in alcoholism. In two ethnically distinct populations, we tested whether the Thr105Ile polymorphism was associated with alcoholism and with harm avoidance, a dimensional measure of anxious personality. Methods: A 5, exonuclease assay (TaqMan) was used to genotype Thr105Ile in psychiatrically interviewed Finnish Caucasian (n= 218) and Plains American Indian (n= 186) alcoholics, along with ethnically matched, psychiatrically interviewed, controls (Finns: n= 313, Plains Indian: n= 140). Results: Ile105 allele frequencies were significantly lower in alcoholics compared with nonalcoholics in both populations (Finns: 0.12 vs. 0.17, ,2= 6, p= 0.015; Plains Indians: 0.03 vs. 0.08, ,2= 5, p= 0.023). Genotype distributions also differed significantly. In Finns, Ile105 showed borderline significance for an association with lower harm avoidance (p= 0.070) after correcting for alcoholism diagnosis. Conclusions: Decreased levels of brain histamine consequent to the Thr105 allele may result in higher levels of anxiety and, as a consequence, vulnerability to alcoholism. [source]

Polymorphisms in IL13 pathway genes in asthma and chronic obstructive pulmonary disease

ALLERGY, Issue 4 2010
B. Beghé
To cite this article: Beghé B, Hall IP, Parker SG, Moffatt MF, Wardlaw A, Connolly MJ, Fabbri LM, Ruse C, Sayers I. Polymorphisms in IL13 pathway genes in asthma and chronic obstructive pulmonary disease. Allergy 2010; 65: 474,481. Abstract Background:, Asthma and chronic obstructive pulmonary disease (COPD) are chronic respiratory diseases involving an interaction between genetic and environmental factors. Interleukin-13 (IL13) has been suggested to have a role in both asthma and COPD. We investigated whether single nucleotide polymorphisms (SNPs) in the IL13 pathway may contribute to the susceptibility and severity of asthma and COPD in adults. Methods:, Twelve SNPs in IL13 pathway genes ,IL4, IL13, IL4RA, IL13RA1, IL13RA2 and STAT6, were genotyped in subjects with asthma (n = 299) and in subjects with COPD or healthy smokers (n = 992). Genetic association was evaluated using genotype and allele models for asthma severity, atopy phenotypes and COPD susceptibility. Linear regression was used to determine the effects of polymorphism on baseline lung function (FEV1, FEV1/FVC). Results:, In asthmatics, three IL13 SNPs , rs1881457(,1512), rs1800925(,1111) and rs20541(R130Q) , were associated with atopy risk. One SNP in IL4RA1 [rs1805010(I75V)] was associated with asthma severity, and several IL13 SNPs showed borderline significance. IL13 SNPs rs1881457(,1512) and rs1800925(,1111) were associated with better FEV1 and FEV1/FVC in asthmatics. IL13 SNPs rs2066960(intron 1), rs20541(R130Q) and rs1295685(exon 4) were associated with COPD risk and lower baseline lung function in the recessive model. In females, but not in males, rs2250747 of the IL13RA1 gene was associated with COPD and lower FEV1. Conclusion:, These data suggest that IL13 SNPs (promoter and coding region) and, to a lesser extent, IL4RA SNPs may contribute to atopy and asthma. We also provide tentative evidence that IL13 SNPs in the coding region may be of significance in COPD susceptibility. [source]

Gas cooking, kitchen ventilation, and asthma, allergic symptoms and sensitization in young children , the PIAMA study

ALLERGY, Issue 5 2006
S. M. Willers
Background:, Several studies reported inconsistent associations between using gas for cooking and respiratory symptoms or lung function in children. Kitchen ventilation characteristics may modify the relationship between gas cooking and respiratory health. The aim of this study was to investigate the effect of kitchen ventilation (while cooking) on the relationship between gas cooking, combustion product dispersal, and respiratory and allergic outcomes in children. Methods:, Data on respiratory and allergic symptoms and diagnoses were collected by yearly questionnaires in a population of over 3000 children participating in a birth cohort study on development of allergy and asthma. At 4 years of age, a sub-sample of 647 children provided blood samples for antibody testing. Data on gas cooking and kitchen ventilation were collected when the children were 5 years old. Based on these data a model was constructed to determine the chance of accumulation of combustion products (CACP) in the kitchen. Results:, No relationship was found between gas cooking and any of the respiratory or allergy outcomes except nasal symptoms. The overall results did not change when the ,CACP' was used as exposure variable instead, while the association for nasal symptoms decreased to borderline significance. Conclusion:, Our results suggest that gas cooking per se is associated with nasal symptoms in young children and not with the other respiratory symptoms that were investigated. Taking kitchen ventilation characteristics into account did not lead to different conclusions in this population where, according to the classification system, the majority of households using gas for cooking have insufficient kitchen ventilation. [source]

School grades and myopia

Seang-Mei Saw
Abstract Aim:, To evaluate the association between school performance and myopia in Singapore children. Methods:, Children aged 10,12 years from two schools in the Singapore Cohort study Of the Risk factors for Myopia (SCORM) were included. Results of a Year 4 standard nation-wide examination were obtained. Cycloplegic autorefraction and A-scan ultrasound biometry measurements were performed in the schools. Results:, The odds ratio for myopia (defined as right eye spherical equivalent at least ,0.5 D) was 2.5 (95% confidence interval 1.4,4.5) for children with average school examination scores in the fourth quartile compared with the first, after adjusting for confounders including reading in books per week and IQ test scores. Similar significant associations were found for English language (p = 0.001) and native language school examination scores (p < 0.001), while the associations with mathematics school examination scores were of borderline significance (p = 0.055). Conclusion:, School grades, a possible indicator of either cumulative engagement in near work activity or intelligence, were positively associated with myopia in Singapore children. [source]

Use of Commercial Sex Workers Among Hispanic Migrants In North Carolina: Implications for the Spread of HIV

Emilio A. Parrado
CONTEXT: Rates of HIV and AIDS have risen among U.S. Hispanics and in migrant-sending regions of Mexico and Central America, pointing to a link between migration and HIV. However, little is known about male migrants' sexual risk behaviors, such as the use of commercial sex workers. METHODS: The prevalence and frequency of commercial sex worker use was examined among 442 randomly selected Hispanic migrants in Durham, North Carolina. Logistic and Poisson regression techniques were used to model predictors of commercial sex worker use, and descriptive data on condom use with commercial sex workers were examined. RESULTS: Twenty-eight percent of respondents reported using the services of a commercial sex worker during the previous year; rates reached 46% among single men and 40% among married men living apart from their wives. Men with spouses in Durham were less likely than other men to use commercial sex workers (odds ratio, 0.1). Among men who used commercial sex workers, the frequency of visits declined with greater education (incidence rate ratio, 0.9) and increased with hourly wage (1.1). Frequency and use declined with years of residence, although the results were of borderline significance. Reported rates of condom use with commercial sex workers were high, but were likely to fall if familiarity with a commercial sex worker increased. CONCLUSIONS: Commercial sex workers represent an important potential source of HIV infection. Educational and behavioral interventions that take into account social context and target the most vulnerable migrants are needed to help migrants and their partners avoid HIV infection. [source]

Use of Illicit Drugs and Erectile Dysfunction Medications and Subsequent HIV Infection among Gay Men in Sydney, Australia

Garrett Prestage PhD
ABSTRACT Introduction., Use of illicit drugs and oral erectile dysfunction medications (OEM) have been associated with risk behavior among gay men. Aim., To determine the effects of illicit drugs and OEM as risk factors for HIV seroconversion in a community-based cohort of HIV-negative homosexually active men in Sydney, Australia. Main Outcome Measures., Drug use in the previous 6 months and at the most recent sexual encounter; Most recent occasions of unprotected and protected anal intercourse; HIV-positive diagnosis. Methods., From June 2001 to June 2007, participants were followed up with 6-monthly detailed behavioral interviews and annual testing for HIV. Detailed information about sexual, drug-using and other behavior was collected. Results., Among 1,427 participants enrolled, 53 HIV seroconverters were identified by June 2007. At baseline, 62.7% reported using illicit drugs in the previous 6 months, including 10.7% who reported at least weekly use. Illicit drug use was associated with unprotected anal intercourse with casual partners (P < 0.001). Use of illicit drugs was associated with increased risk of HIV infection at a univariate level, and this risk increased with greater frequency of use. This was also true of the use of OEM. Use of each type of illicit drug was included in multivariate analysis, and after controlling for sexual risk behaviors, only use of OEM remained significantly predictive of HIV infection (Hazard ratios [HR] = 1.75, CI = 1.31,2.33, P < 0.001), although amyl nitrite was of borderline significance (HR = 1.26, CI = 0.98,1.62, P = 0.074). Conclusion., The association between drug use and increased risk of HIV infection was strongest for drugs used specifically to enhance sexual pleasure, particularly OEM. The risk of infection was substantially increased when both OEM and methamphetamine were used. Within more "adventurous" gay community subcultures, the interconnectedness of sexual behavior and drug use may be key to understanding HIV risk and is an appropriate priority in HIV-prevention efforts in this population. Prestage G, Jin F, Kippax S, Zablotska I, Imrie J, and Grulich A. Use of illicit drugs and erectile dysfunction medications and subsequent HIV infection among gay men in Sydney, Australia. J Sex Med 2009;6:2311,2320. [source]

Obstetric management of a woman's first delivery and the implications for pelvic floor surgery in later life

Ramalingam Uma
Objective To determine the influence of intrapartum care during a first delivery on the risk of pelvic floor surgery in later life. Design Nested case,control study with record linkage of a historical cohort and a current morbidity database. Setting Hospital births in Dundee 1952,1966. Population The 7556 primiparous women from the Walker cohort. Methods The cases (n= 352) were women who delivered a first singleton baby at term (,37 weeks) and subsequently had pelvic floor surgery. Controls (n= 1403) were women who delivered their first baby during the same time period and did not undergo surgery. Univariate and multivariate logistic regression analyses were performed taking account of demographic, anthropometric and obstetric factors. Main outcome measure Pelvic floor surgery. Results Caesarean section was associated with a reduced risk of pelvic floor surgery compared with spontaneous vaginal delivery (odds ratio 0.16, 95% CI 0.05,0.55). Forceps delivery and infant birthweight >4.0 kg were not identified as significant risk factors (OR 0.94, 95% CI 0.71, 1.25, and OR 0.94, 95% CI 0.50, 1.75, respectively). Episiotomy and prolonged labour (>12 hours) may be associated risk factors but were of borderline significance (OR 1.46, 95% CI 0.99, 2.10, and OR 1.51, 95% CI 1.00, 2.27). Conclusion Caesarean section in a first pregnancy appears to protect against pelvic floor surgery in later life. [source]

Chemotherapy with 5-fluorouracil and a platinum compound improves outcomes in metastatic small bowel adenocarcinoma,

CANCER, Issue 8 2008
Michael J. Overman MD
Abstract BACKGROUND. Metastatic small bowel adenocarcinoma (SBA) has a poor prognosis. Because of the rarity of SBA, only a few studies have evaluated the role of chemotherapy in the treatment of metastatic SBA; thus, the benefit, if any, of adding a platinum compound to fluorouracil (5-FU) is unknown. The objective of this retrospective study was to determine whether the addition of a platinum compound to 5-FU provided any benefit in the treatment of patients with metastatic SBA. METHODS. The authors identified 80 patients with metastatic SBA who were treated with chemotherapy at the University of Texas M. D. Anderson Cancer Center between 1978 and 2005. Response rates, progression-free survival (PFS), and overall survival (OS) were compared between patients who received 5-FU and a platinum compound and patients who received other chemotherapy combinations. RESULTS. The median patient age was 53 years. The primary tumor site was the jejunum in 35 patients (43%), duodenum in 30 patients (38%), ileum in 6 patients (8%), and nonspecified small bowel in 9 patients (11%). Of all 80 patients, 29 patients (36%) received 5-FU and a platinum compound, 41 patients (51%) received 5-FU without a platinum compound, and 10 patients (13%) received non-5-FU,based treatment. Compared with other chemotherapy regimens, treatment with 5-FU and a platinum agent resulted in a higher response rate (46% vs 16% with other regimens; P = .01) and longer median PFS (8.7 months vs 3.9 months; P , .01) but not better OS (14.8 months vs 12 months; P = .1). In multivariate analysis, treatment with 5-FU and a platinum compound was a significant predictor of response (odds ratio, 4.5; 95% confidence interval [CI], 1.3-15.8; P = .02) and PFS (hazard ratio. 0.49; 95% CI, 0.29-0.84; P = .01) but only reached borderline significance for OS (hazard ratio, 0.63; 95% CI, 0.37-1.07; P = .08). CONCLUSIONS. To the authors' knowledge, the current analysis represents the largest number of patients with metastatic SBA treated with chemotherapy in the literature, and the results suggested that the combination of 5-FU and a platinum compound leads to a higher response rate and PFS compared with other chemotherapy regimes. The authors concluded that prospective investigation of platinum analogues in the treatment of SBA is warranted. Cancer 2008. © 2008 American Cancer Society. [source]

Prognostic factors in the nonsurgical treatment of esophageal carcinoma with radiotherapy or radiochemotherapy

CANCER, Issue 8 2005
The importance of pretreatment hemoglobin levels
Abstract BACKGROUND The current study was performed to evaluate prognostic factors for overall survival (OS), distant metastasis (DM), and local failure (LF) in patients with Stage II/III esophageal carcinoma. METHODS The following potential prognostic factors were retrospectively investigated in 124 patients treated with radiotherapy (RT) alone or with radiochemotherapy: age, gender, performance status, tumor location, tumor length, histology, histologic grade, T classification, N classification, International Union Against Cancer stage, chemotherapy, RT dose, and pre-RT hemoglobin level. RESULTS Using univariate analysis (Kaplan,Meier method), pre-RT hemoglobin level, RT dose, tumor length, chemotherapy, and performance status were significantly associated with OS. Hemoglobin levels of 12.1,14.0 g/dL were associated with the best OS, followed by , 14.1 g/dL and , 12.0 g/dL. DM was significantly influenced by tumor length, RT dose, N classification, and performance status. LF was significantly influenced by pre-RT hemoglobin level, RT dose, and tumor length. Using multivariate analysis (Cox proportional hazard model), pre-RT hemoglobin maintained significance for OS (P < 0.001) and LF (P < 0.001), RT dose for OS (P = 0.001), DM (P = 0.031), and LF (P < 0.001), tumor length for OS (P = 0.003), DM (P = 0.017), and LF (P = 0.033), and chemotherapy for OS (P = 0.027). N classification was of borderline significance for DM (P = 0.054). Performance status lost significance for OS (P = 0.73) and LF (P = 0.22). CONCLUSIONS The strongest predictors for outcome in Stage II/III esophageal carcinoma were RT dose, tumor length, pre-RT hemoglobin level, and chemotherapy. The pre-RT hemoglobin level was an independent prognostic factor significantly associated with OS and LF. A hemoglobin level of 12.1,14 g/dL resulted in a better prognosis than hemoglobin levels , 14 g/dL and , 12 g/dL. Cancer 2005. © 2005 American Cancer Society. [source]

The role of extreme phenotype selection studies in the identification of clinically relevant genotypes in cancer research,

CANCER, Issue 7 2002
Jose Luis Perez-Gracia M.D.
Abstract The investigation of genetic alterations that may be related to the prognosis of patients with malignant disease has become a frequently used strategy in recent years. Although some conclusions have been reached in certain studies, the complexity and the multifactorial nature of most neoplastic diseases makes it difficult to identify clinically relevant information, and the results of some studies have been of borderline significance or have been conflicting. In contrast, the identification and the study of patients or families with very characteristic phenotypes have yielded outstanding results in the identification of the genetic characteristics underlying such phenotypes. Although, in most cases, the individuals who are selected for these types of studies are characterized by a negative phenotype (i.e., individuals who are at increased risk for developing a specific disease), a few studies have been directed toward individuals with phenotypes that imply an unusually good prognosis (i.e., individuals who present with a decreased risk for developing specific diseases despite an important exposure to well-known risk factors). Therefore, it seems logical to develop this strategy further as a valid methodology for the study of other diseases, such as cancer. The study of individuals with phenotypes that imply an extremely good prognosis, such as long-term survivors of theoretically incurable malignancies or individuals who seem to be protected against a certain neoplastic disorder despite having a markedly increased risk for its development, may unveil genetic alterations that explain such characteristic phenotypes and may provide potentially useful therapeutic targets against these diseases. Cancer 2002;95:1605,10. © 2002 American Cancer Society. DOI 10.1002/cncr.10877 [source]

Brain metastases in locally advanced nonsmall cell lung carcinoma after multimodality treatment

CANCER, Issue 3 2002
Risk factors analysis
Abstract BACKGROUND Brain metastases (BM) are frequent sites of initial failure in patients with locally advanced nonsmall cell lung cancer (LAD-NSCLC) undergoing multimodality treatments (MMT). New treatment and follow-up strategies are needed to reduce the risk of BM and to diagnose them early enough for effective treatment. METHODS The incidence rate of BM as the first site of recurrence in 112 patients with LAD-NSCLC treated with the same MMT protocol was calculated. The influence of patient, disease, and treatment-related factors on the incidence of BM and on the time-to-brain recurrence (TBR) was analyzed. RESULTS BM as the first site of failure was observed in 25 cases (22% of the study population and 29% of all recurrences). In 18 of those cases, the brain was the exclusive site of recurrence. Median TBR was 9 months. The 2-year actuarial incidence of BM was 29%. Central nervous system (CNS) recurrence was more common in patients younger than 60 years (P = 0.006) and in whom bulky (, 2 cm) mediastinal lymph nodes were present (P = 0.02). TBR was influenced by age (P = 0.004) and by bulky lymph node disease (P = 0.003). Multivariate analysis confirmed the prognostic role of age, whereas the presence of clinical bulky mediastinal lymph nodes was of borderline significance. CONCLUSIONS Our study confirmed a high rate of BM in patients with LAD-NSCLC submitted to MMT. Most of these CNS recurrences were isolated and occurred within 2 years of initial diagnosis. Age younger than 60 years was associated with an increased risk of BM and reduced TBR, whereas the presence of clinical bulky mediastinal lymph nodes was of borderline significance. Although our data require further validation in future studies, our results suggest that additional trials on prophylactic cranial irradiation and on intensive radiologic follow-up should focus on these high-risk populations. Cancer 2002;95:605,12. © 2002 American Cancer Society. DOI 10.1002/cncr.10687 [source]

The effect of fluoride gel on incipient carious lesions in a low-caries child population

Gert-Jan Truin
Abstract,,, Objectives:, Secondary analyses were performed to study the cariostatic efficacy of semi-annual professional fluoride gel application on incipient carious lesions in low-caries children initially aged 9.5,11.5 years. Methods:, Double-blind randomized controlled clinical trial. Results:, The mean treatment effect of fluoride gel for enamel and dentinal caries lesions after 4 years' follow-up was 0.92 D2,3FS and 0.20 D3FS, respectively. When enamel lesions were included in the DFS count (i.e. D2,3FS), the preventive fraction (PF) showed borderline significance (23%; P = 0.05). No significant treatment effect of professionally applied fluoride gel was found for D2,3FS and D3FS scores of the second molars. The PF for D2,3FS of occlusal, approximal, buccal and lingual surfaces and for buccal and palatal pits and fissures differed not significantly. Conclusion:, Professionally applied fluoride gel showed no statistically significant caries-inhibiting effect on both enamel and dentine lesions in the permanent dentition of low-caries children. [source]