Alcohol consumption and persistent infection of high-risk human papillomavirus.

Alcohol consumption is a possible co-factor of high-risk human papillomavirus (HR-HPV) persistence, a major step in cervical carcinogenesis, but the association between alcohol and continuous HPV infection remains unclear. This prospective study identified the association between alcohol consumption and HR-HPV persistence. Overall, 9230 women who underwent screening during 2002-2011 at the National Cancer Center, Korea were analysed in multivariate logistic regression. Current drinkers [odds ratio (OR) 2·49, 95% confidence interval (CI) 1·32-4·71] and drinkers for ⩾5 years (OR 2·33, 95% CI 1·17-4·63) had a higher risk of 2-year HR-HPV persistence (HPV positivity for 3 consecutive years) than non-drinkers and drinkers for <5 years, respectively (vs. HPV negativity for 3 consecutive years). A high drinking frequency (⩾twice/week) and a high beer intake (⩾3 glasses/occasion) had higher risks of 1-year (OR 1·80, 95% CI 1·01-3·36) HPV positivity for 2 consecutive years) and 2-year HR-HPV persistence (OR 3·62, 95% CI 1·35-9·75) than non-drinkers. Of the HPV-positive subjects enrolled, drinking habit (OR 2·68, 95% CI 1·10-6·51) and high consumption of beer or soju (⩾2 glasses/occasion; OR 2·90, 95% CI 1·06-7·98) increased the risk of 2-year consecutive or alternate HR-HPV positivity (vs. consecutive HPV negativity). These findings suggest that alcohol consumption might increase the risk of cervical HR-HPV persistence in Korean women.

Efficiency of professional tooth brushing before ultrasonic scaling.

OBJECTIVES: This study aimed to examine the effect of dental plaque biofilm removal with a toothbrush, an interdental brush and dental floss by a dental hygienist prior to ultrasonic scaling on treatment times and client satisfaction. METHODS: This study was conducted among adults who received scaling after agreeing to participate in this study at a dental clinic in Seoul, Korea, from July to September 2012. Thirty-seven subjects received modified scaling (M-scaling) which is ultrasonic scaling after plaque control with a toothbrush and dental floss by a dental hygienist, and 37 subjects received routine ultrasonic scaling (R-scaling). Univariate and multivariate analyses and chi-squared and t-tests were conducted using SAS. This study was approved by the Kangwon Institutional Review Board. RESULTS: Significant differences were found between the outcomes of M- and R-scaling for both the ultrasonic scaling time (M-scaling, 7.41 ± 6.18 min; R-scaling, 23.22 ± 6.92 min) and the total tooth cleaning time (M-scaling, 15.92 ± 7.70 min; R-scaling, 23.22 ± 6.92 min) (P < 0.001). Subject satisfaction with the scaling process was not significantly different between M-scaling (4.54 ± 0.80) and R-scaling (4.84 ± 0.44). CONCLUSIONS: These findings indicated that removing the dental plaque biofilm with a toothbrush and dental floss by a hygienist before scaling with an ultrasonic device was more effective in reducing the working time of the dental hygienist.

Association between pre-donation serum uric acid concentration and change in renal function after living kidney donation in women.

BACKGROUND: Reduction in renal mass after unilateral nephrectomy causes functional and structural changes in the remaining kidney. AIM: We aimed to investigate the association between pre-donation serum uric acid (SUA) concentration and the change in renal function after living kidney donation. METHODS: This retrospective study included 413 living kidney donors from a single centre. We collected medical history and laboratory findings at baseline and 6 months after donation. Renal function was assessed by calculating the estimated glomerular filtration rate (eGFR) using the Chronic Kidney Disease Epidemiology Collaboration equation. Main outcomes were the percentage change in eGFR from before to 6 months after donation and the percentage of patients whose eGFR decreased by >25% after donation compared with the pre-donation baseline value. RESULTS: Mean age was 40 ± 11 years, and eGFR was 106 ± 14 mL/min/1.73 m(2). In women, the SUA concentration was linearly associated with the change in eGFR after donation independently of baseline eGFR (standardised coefficient - 0.16, P = 0.04). Multiple logistic analysis showed that a 59.5 µmol/L increase in baseline SUA concentration was associated with a 1.7-fold higher risk of a > 25% decrease in eGFR after donor nephrectomy (95% confidence interval, 1.2-2.5; P = 0.007) in women. In contrast, SUA concentration was not an independent risk factor of decrease in eGFR after donor nephrectomy in men. CONCLUSIONS: Pre-donation SUA concentration is associated independently with the change in renal function after donor nephrectomy in women but not in men.

Assessment of extent of breast cancer: comparison between digital breast tomosynthesis and full-field digital mammography.

AIM: To compare the accuracy of digital breast tomosynthesis (DBT) and full-field digital mammography (FFDM) in preoperative assessment of local extent of breast cancer. MATERIALS AND METHODS: Lesion sizes of breast cancers on DBT and FFDM images were independently evaluated by breast radiologists. Each lesion was flagged as either mis-sized or not depending on whether the assessment of size at imaging was within 1 cm of the lesion size at surgery. Additional analyses were made by mammographic parenchymal density and by lesion size, using 2 cm as the boundary to separate the two subgroups. Statistical comparisons were performed using a repeated measures linear model on the percent mis-sized. P-values < 0.05 were considered statistically significant. RESULTS: The dataset included 173 malignant breast lesions (mean size 23.8 mm, 43% of lesions were ≤2 cm in size) in 169 patients, two-thirds of which had heterogeneously or extremely dense breasts. Overall, the percentage of lesions mis-sized at DBT was significantly lower than at FFDM (19% versus 29%, p = 0.003). There was significantly less mis-sizing at DBT in both heterogeneously dense breasts (11.1% difference between DBT and FFDM, p = 0.016) and extremely dense breasts (15.8% difference, p = 0.024). DBT also had significantly less mis-sizing than FFDM in the subgroup of lesions that were ≤2 cm in size (14.7% difference, p = 0.005). CONCLUSION: DBT was significantly superior to FFDM for the evaluation of lesion size overall, and specifically for small lesions and for lesions in dense breasts. The superiority of DBT versus FFDM increased with parenchymal density.

Combination treatment with corticosteroid, cyclosporine A, and mycophenolate in refractory nephrotic syndrome.

BACKGROUND/AIMS: Refractory nephrotic syndrome (NS) is problematic because the optimal therapy for this disease is unclear and because persistent NS progresses eventually to end-stage renal disease. We report our experience using a combination of corticosteroid, cyclosporine A (CsA), and mycophenolate mofetil (MMF) to treat 10 refractory NS patients. METHODS: Ten refractory NS patients, who showed resistance to corticosteroid and CsA, were treated with triple immunosuppressive therapy. Cyclophosphamide and MMF had been used previously in 6 patients, but had failed to induce remission. RESULTS: Triple immunosuppressive therapy was discontinued after 4 months in 1 patient because of progressive azotemia. Partial remission was achieved in 9 of the 10 patients after 10 months, and remission was maintained during the treatment (urine protein to creatinine ratio, mg/mg, baseline vs. 12th month; 5.7 ± 1.8 vs. 1.4 ± 0.7). Renal function was preserved in these 9 patients (estimated GFR, ml/min/1.73 m2, baseline vs. 12th month; 71.4 ± 29.1 vs. 68.9 ± 31.5). Of the 7 patients who discontinued triple immunosuppressive therapy, remission and renal function were maintained in 4 patients. CONCLUSION: Triple immunosuppressive therapy significantly reduced proteinuria and preserved renal function in refractory NS patients, indicating a promising role of this therapy for refractory NS.

Urinary angiotensinogen levels reflect the severity of renal histopathology in patients with chronic kidney disease.

BACKGROUND/AIMS: Recent studies have suggested that urinary angiotensinogen (AGT) reflects the activity of the intrarenal renin angiotensin system (RAS), which is involved in tissue injury in patients with chronic kidney disease. In this study, we investigated whether urinary AGT directly reflected the severity of histopathology in such patients. METHODS: AGT was measured using a sandwich enzyme-linked immunosorbent assay (ELISA) on urine and plasma samples obtained from 58 patients on the day of renal biopsy. We measured the urinary transforming growth factor (TGF)-beta1, a representative cytokine of fibrogenic property, and analyzed the correlation among urinary TGF-beta1, urinary AGT, and the severity of renal injury. Mesangial proliferation, glomerulosclerosis, tubular atrophy and interstitial fibrosis were scored for the biopsied tissues. RESULTS: Urinary AGT levels correlated positively with proteinuria, urinary TGF-beta1 levels and diastolic blood pressure, but negatively with the estimated glomerular filtration rate (GFR). Urinary AGT concentrations were increased in patients with severe glomerulosclerosis, tubular atrophy and interstitial fibrosis. CONCLUSION: Urinary AGT levels correlated with the deterioration of renal function in patients with chronic kidney disease and reflected the histological severity of renal injury.

Clinical Impact of a Protocolized Kidney Donor Follow-up System.

BACKGROUND: Adequate kidney donor management after donation is increasingly emphasized due to concerns of renal function impairment after nephrectomy with increasing life expectancy. In this study, the clinical impact of a protocolized kidney donor follow-up system by nephrologists was evaluated. METHODS: A total of 427 living kidney donors underwent nephrectomy from January 2010 to December 2014 and were followed for at least 2 years at the Samsung Medical Center. Donors were followed-up by nephrologists after the establishment of a donor clinic with systemized protocols in January 2013. The primary outcomes were incidence of post-donation low estimated glomerular filtration rate (eGFR) and renal function adaptability. Secondary outcomes were changes in compliance and incidence of hyperuricemia and microalbuminuria. RESULTS: The patients were divided into 2 groups according to the time of nephrectomy: the pre-donor clinic period (n = 182) and the donor clinic period (n = 172). Preoperative eGFR in patients in the pre-donor clinic period was higher than that in patients in the donor clinic period. After donation, poor renal adaptation was less frequent in the donor clinic period compared to the pre-donor clinic period. Low eGFR tended to be less common during the donor clinic period. Shorter mean outpatient clinic visit intervals with more visits within 6 months after donation and earlier detection of de novo hyperuricemia were found during the donor clinic period. CONCLUSION: A protocolized donor clinic run by nephrologists may improve post-nephrectomy renal outcomes and compliance and facilitate better management of potential risk factors of chronic kidney disease in donors.

Dexamethasone protects primary cultured hepatocytes from death receptor-mediated apoptosis by upregulation of cFLIP.

Dexamethasone (DEX) pretreatment protected hepatocytes from TNF-alpha plus actinomycin D (ActD)-induced apoptosis by suppressing caspase-8 activation and the mitochondria-dependent apoptosis pathway. DEX treatment upregulated cellular FLICE inhibitory protein (cFLIP) expression, but did not alter the protein levels of Bcl-2, Bcl-xL, Mcl-1, and cIAP as well as Akt activation. The increased cFLIP mRNA level by DEX was inhibited by ActD, indicating that DEX upregulates cFLIP expression at the transcriptional step. DEX also inhibited Jo2-mediated hepatocyte apoptosis by blocking the formation of the death-inducing signaling complex and caspase-8 activation. Specific downregulation of cFLIP expression using siRNA reversed the antiapoptotic effect of DEX by increasing caspase-8 activation. Moreover, DEX administration into mice increased cFLIP expression in the liver and prevented Jo2-induced hepatic injury by inhibiting caspase-8 and -3 activities. Our results indicate that DEX exerts a protective role in death receptor-induced in vitro and in vivo hepatocyte apoptosis by upregulating cFLIP expression.

A case of scapulothoracic dissociation with brachial plexus injury: magnetic resonance imaging findings.

Scapulothoracic dissociation is defined as violent lateral or rotational displacement of the shoulder girdle from its thoracic attachments with severe neurovascular injury. We describe the radiographic and associated magnetic resonance (MR) imaging findings of a case of scapulothoracic dissociation with brachial plexus injury in a 17-year-old man, and include a review of the relevant literature.

The incidence and clinical outcome of YMDD mutants in hepatitis B surface antigen-positive renal allograft recipients after prolonged lamivudine therapy.

Although lamivudine (LAM) is a potent inhibitor of hepatitis B virus (HBV), prolonged therapy may induce the development of LAM-resistant strains, YMDD mutants. Although YMDD mutants have impaired replication that leads to a benign clinical course compared with wild-type virus, some immunosuppressive agents may enhance replication of YMDD mutants, causing a severe hepatitis flare. We retrospectively investigated the incidence and clinical outcomes of YMDD mutants in renal allograft recipients on immunosuppressive treatment. Clinical records of 25 renal allograft recipients, who underwent renal transplantation between December 1997 and February 2006 were hepatitis B surface antigen positive at the time of transplantation, were reviewed. All patients received LAM treatment after renal transplantation. Over 9 to 98 months of follow-up, 16 patients (64.0%) maintained undetectable HBV DNA levels; however, 9 patients (36.0%) showed persistent or increased levels of HBV DNA. Seven were identified as having developed YMDD mutants. Although genotypic analysis was not performed, YMDD mutants were strongly suspected in another two patients, who developed severe hepatic dysfunction combined with high levels of HBV viremia at close to 2 years of LAM therapy. One patient recovered after hepatic transplantation and another patient died of hepatic failure. In conclusion, the incidence of YMDD mutants was similar to that of nonimmunosuppressed individuals; however, the presence of these mutants made it more likely for severe liver disease to develop in renal transplant recipients. Therefore, close monitoring for the development of YMDD mutants should be performed during LAM treatment, especially in this group of patients.

Prevalence, demographic variation and psychological correlates of exposure to police victimisation in four US cities.

Aims Victimisation by the police is purported to be widespread in cities in the USA, but there is limited data on police-public encounters from community samples. This is partly due to an absence of measures for assessing police violence exposure from the standpoint of civilians. As such, the demographic distribution and mental health correlates of police victimisation are poorly understood. The aims of this study were to present community-based prevalence estimates of positive policing and police victimisation based on assessment with two novel measures, and to test the hypotheses that (1) exposure to police victimisation would vary across demographic groups and (2) would be associated with depression and psychological distress. METHODS: The Survey of Police-Public Encounters study surveyed adults residing in four US cities to examine the prevalence, demographic distribution and psychological correlates of police victimisation. Participants (N = 1615) completed measures of psychological distress (K-6 scale), depression (Patient Health Questionnaire 9) and two newly constructed measures of civilian-reported police-public encounters. Both measures were developed to assess police victimisation based on the WHO domains of violence, which include physical violence (with and without a weapon, assessed separately), sexual violence (inappropriate sexual contact, including public strip searches), psychological violence (e.g., threatening, intimidating, stopping without cause, or using discriminatory slurs) and neglect (police not responding when called or responding too late). The Police Practices Inventory assesses lifetime history of exposure to positive policing and police victimisation, and the Expectations of Police Practices Scale assesses the perceived likelihood of future incidents of police victimisation. Linear regression models were used to test for associations between police-public encounters and psychological distress and depression. RESULTS: Psychological violence (18.6%) and police neglect (18.8%) were commonly reported in this sample and a substantial minority of respondents also reported more severe forms of violence, specifically physical (6.1%), sexual (2.8%) and physical with a weapon (3.3%). Police victimisation was more frequently reported by racial/ethnic minorities, males, transgender respondents and younger adults. Nearly all forms of victimisation (but not positive policing) were associated with psychological distress and depression in adjusted linear regression models. CONCLUSIONS: Victimisation by police appears to be widespread, inequitably distributed across demographic groups and psychologically impactful. These findings suggest that public health efforts to both reduce the prevalence of police violence and to alleviate its psychological impact may be needed, particularly in disadvantaged urban communities.

Predictive Factors of Renal Adaptation After Nephrectomy in Kidney Donors.

BACKGROUND: Despite compensatory hyperfiltration in remaining nephrons following donor nephrectomy, some donors show impaired renal adaptation and low estimated glomerular filtration rate (eGFR). We investigated the factors predicting early renal adaptation after nephrectomy and identified kidney donors at risk of inadequate renal adaptation. METHODS: A total of 265 living kidney donors from 2010 to 2013 were retrospectively analyzed. Renal function was serially followed for 6 months after the operation. Regression analyses were performed to identify the independent predictors of low eGFR (eGFR <60 mL/min/1.73 m2) and impaired renal adaptation (%Modification of Diet in Renal Disease [MDRD] <66% of baseline eGFR). RESULTS: A total of 148 donors belonged to the low eGFR group, and changes in eGFR (ΔeGFR) at postoperative (PO) 1 day and 1 month were identified as independent predictors of low eGFR. Impaired renal adaptation was related to age, ΔeGFR PO 2-3 days, and ΔeGFR PO 1 month. Early renal adaptation was associated with age, male gender, and residual kidney computerized tomography angiography (CTA) volume. The best sensitivity and specificity were obtained with a cutoff value of ΔeGFR 31 at PO 1 day and 1 month for predicting low eGFR and with a value of ΔeGFR 27 at PO 2-3 days and 1 month for predicting impaired renal adaptation. CONCLUSIONS: Our study showed that the degree of early renal adaptation determines subsequent renal function in kidney donors. Closer monitoring and management may be required in old or male donors with small residual CTA kidney volume as well as donors with persistent ΔeGFR >27 within 1 month of nephrectomy.

The association of uterine cervical microbiota with an increased risk for cervical intraepithelial neoplasia in Korea.

Recent studies have suggested potential roles of the microbiome in cervicovaginal diseases. However, there has been no report on the cervical microbiome in cervical intraepithelial neoplasia (CIN). We aimed to identify the cervical microbiota of Korean women and assess the association between the cervical microbiota and CIN, and to determine the combined effect of the microbiota and human papillomavirus (HPV) on the risk of CIN. The cervical microbiota of 70 women with CIN and 50 control women was analysed using pyrosequencing based on the 16S rRNA gene. The associations between specific microbial patterns or abundance of specific microbiota and CIN risk were assessed using multivariate logistic regression, and the relative excess risk due to interaction (RERI) and the synergy index (S) were calculated. The phyla Firmicutes, Actinobacteria, Bacteroidetes, Proteobacteria, Tenericutes, Fusobacteria and TM7 were predominant in the microbiota and four distinct community types were observed in all women. A high score of the pattern characterized by predominance of Atopobium vaginae, Gardnerella vaginalis and Lactobacillus iners with a minority of Lactobacillus crispatus had a higher CIN risk (OR 5.80, 95% CI 1.73-19.4) and abundance of A. vaginae had a higher CIN risk (OR 6.63, 95% CI 1.61-27.2). The synergistic effect of a high score of this microbial pattern and oncogenic HPV was observed (OR 34.1, 95% CI 4.95-284.5; RERI/S, 15.9/1.93). A predominance of A. vaginae, G. vaginalis and L. iners with a concomitant paucity of L. crispatus in the cervical microbiota was associated with CIN risk, suggesting that bacterial dysbiosis and its combination with oncogenic HPV may be a risk factor for cervical neoplasia.

A multiplex-PCR/RFLP procedure for simultaneous CYP2E1, mEH and GSTM1 genotyping.

Inter-individual variation in metabolism of environmental toxicants, which is attributed to genetic polymorphism, may be a major risk factor in determining who will develop adverse health effects. This priority research area is the focus of many laboratories, and new techniques need to be developed to enhance the efficiency in generating data. We have developed and validated a new multiplex-polymerase chain reaction (PCR), restriction fragment length polymorphism (RFLP) procedure for simultaneous genotyping of cytochrome P450 II E1 (CYP2E1), microsomal epoxide hydrolase (mEH), and glutathione S-transferase mu (GSTM1). Enzymes from these three polymorphic genes are involved with the phase I and II metabolism of a variety of environmental toxicants. Therefore, simultaneous characterization of these genes will not only reduce costs but will increase the efficiency of data collection, thereby contributing to health risk assessment efforts.

Variant metabolizing gene alleles determine the genotoxicity of benzo[a]pyrene.

Understanding the mechanisms involved with genetic susceptibility to environmental disease is of major interest to the scientific community. We have conducted an in vitro study to elucidate the involvement of polymorphic metabolizing genes on the genotoxicity of benzo[a]pyrene (BP). Blood samples from 38 donors were treated with BP and the induction of sister chromatid exchanges (SCE) and chromosome aberrations (CA) were evaluated. The latter is based on the tandem-probe fluorescence in situ hybridization (FISH) assay. The data indicate that the induction of genotoxicity was clearly determined by the inherited variant genotypes for glutathione-S-transferase (GSTM1) and microsomal epoxide hydrolase (EH). In a comparison of the two biomarkers, the CA biomarker shows a more definite association with the genotypes than does SCE. For example, the presence of the GSTM1 null genotype (GSTM1 0/0) is responsible for the highest level and significant induction of CA, irrespective of the presence of other genotypes in the different donors. This effect is further enhanced significantly by the presence of the excessive activation EH gene allele (EH4*) and decreased by the reduced activation EH gene allele (EH3*). Overall, the modulation of genotoxicity by the susceptibility genotypes provides support of their potential involvement in environmental cancer. Furthermore, the data indicate that the variant enzymes function independently by contributing their metabolic capability toward the expression of biologic activities. Therefore, studies like this one can be used to resolve the complexity of genetic susceptibility to environmental disease in human.

Usefulness of genetic susceptibility and biomarkers for evaluation of environmental health risk.

Recent attention is focused on understanding the genetic basis for individual susceptibility to the development of chronic disease. An emphasis is concentrated on establishing an association between inheritance of polymorphic chemical metabolizing genes and development of environmental cancer (e.g., lung cancer among cigarette smokers). The early reports of such associations have been very encouraging. However, some reported positive associations were not substantiated in subsequent studies using larger sample sizes and different ethnic populations. In this review, some confounding factors that contribute to the discrepancies are presented (e.g., ethnic-dependent distribution of variant gene alleles, differential expression of metabolizing genes, and inadequate study design). It is possible that the precision of the association can be improved if the mentioned investigations are complemented with concurrent studies of biological activities/effects. The usefulness of integrating metabolic susceptibility with biomarker measurement for understanding the development of lung cancers is presented. The importance of using adequate sample size and experimental design is emphasized. Development of a reliable approach for prediction of environmental disease not only will provide fundamental information regarding the genetic basis of human disease but will be useful for reducing disease burden in the population and for advancing patient care. Environ. Mol. Mutagen. 37:215-225, 2001. © 2001 Wiley-Liss, Inc.

Abnormalities of glomerular basement membrane in acute postinfectious glomerulonephritis.

The segmental abnormalities of glomerular basement membrane (GBM) were studied by electron microscopy in 69 renal biopsies with acute postinfectious glomerulonephritis (APGN) and correlated with the general morphologic features and clinical findings. Thirty-six were children and 33 were adults. Biopsies were grouped into three stages by light microscopy: exudative stage (25 patients), exudative-proliferative stage (26) and proliferative stage (18). Subepithelial deposits or "humps" were present in 59 patients (86%). The frequency of humps was significantly lower at the proliferative stage than that noted in the earlier biopsies (p less than 0.01). Intramembranous, subendothelial and mesangial deposits were shown in 83% to 88% of the patients. The overall frequency of GBM abnormalities was 45%, showing significantly higher frequency in children than in adults (p less than 0.01). Dissolving subepithelial deposits were often present in the foci with GBM abnormalities. The GBM lesions were not related to more severe clinical manifestations or outcomes, but tended to occur more frequently in later biopsies (p less than 0.01). These results suggest that abnormalities of GBM in APGN are more often present than formerly assumed, especially in children, and could be a normal response to subepithelial deposits. The occurrence of these lesions in other types of immune-related glomerulonephritis may be considered along the same lines.

Biomarker monitoring for health risk based on sensitivity to environmental mutagens.

Ongoing human and environmental genome programs have generated a tremendous amount of information regarding the genetic basis for human disease. The information can be used to enhance existing bioassays, as well as to develop new bioassays for improving human monitoring with the goal of disease prevention. In this review, some biomarkers that can be used for the purpose are presented, with an emphasis on using biomarkers to monitor human sensitivity to environmental mutagens. The application of biomarkers in clarifying the role of inherited and acquired susceptibility for developing environmental disease will be discussed. We emphasize the use of biomarkers that can detect mutagen sensitivity and DNA repair deficiency in the humans as an indication of susceptibility to disease. Such sensitivity can be either genetically determined or acquired from the exposure to environmental mutagens.