bluuebunny/crossref_metadata_2025 huggingface dataset:
Genetic Variation in the Vitamin D Receptor (VDR) and the Vitamin D–Binding Protein (GC) and Risk for Colorectal Cancer: Results from the Colon Cancer Family Registry
Authors: Poynter Jenny N. , Jacobs Elizabeth T. , Figueiredo Jane C. , Lee Won H. , Conti David V. , Campbell Peter T. , Levine A. Joan , Limburg Paul , Le Marchand Loic , Cotterchio Michelle , Newcomb Polly A. , Potter John D. , Jenkins Mark A. , Hopper John L. , Duggan David J. , Baron John A. , Haile Robert W.
Published: February 2010

Epidemiologic evidence supports a role for vitamin D in colorectal cancer (CRC) risk. Variants in vitamin D–related genes might modify the association between vitamin D levels and CRC risk. In this analysis, we did a comprehensive evaluation of common variants in the vitamin D receptor (VDR) and the vitamin D–binding protein (GC; group-specific component) genes using a population-based case–unaffected sibling control design that included 1,750 sibships recruited into the Colon Cancer Family Registry. We also evaluated whether any associations differed by calcium supplement use, family history of CRC, or tumor characteristics. Heterogeneity by calcium and vitamin D intake was evaluated for a subset of 585 cases and 837 sibling controls who completed a detailed food frequency questionnaire. Age- and sex-adjusted associations were estimated using conditional logistic regression. Overall, we did not find evidence for an association between any single-nucleotide polymorphism (SNP) in VDR or GC and risk for CRC (range of unadjusted P values 0.01-0.98 for VDR and 0.07-0.95 for GC). None of these associations was significant after adjustment for multiple comparisons. We also found no evidence that calcium or vitamin D intake (food and supplement) from the food frequency questionnaire modified the association estimates between VDR and GC SNPs and CRC. We did observe associations between SNPs in GC and microsatellite unstable CRC, although these results should be confirmed in additional studies. Overall, our results do not provide evidence for a role of common genetic variants in VDR or GC in susceptibility to CRC. Cancer Epidemiol Biomarkers Prev; 19(2); 525–36
Long-term Postmenopausal Hormone Therapy and Endometrial Cancer
Authors: Razavi Pedram , Pike Malcolm C. , Horn-Ross Pamela L. , Templeman Claire , Bernstein Leslie , Ursin Giske
Published: February 2010

Estrogen-alone therapy (ET) or estrogen and progestin (EPT) as menopausal hormone therapy (HT) has been commonly used to alleviate menopausal symptoms. Treatments containing ≥10 days per month of progestin are considered relatively safe with respect to endometrial cancer risk. However, the endometrial safety of long-term EPT regimens is uncertain. We conducted a case-control study of 311 invasive endometrial cancer cases and 570 controls nested within the California Teachers Study cohort. We used unconditional logistic regression to obtain odds ratios (OR) and 95% confidence intervals (95% CI) for the association between long-term HT use and endometrial cancer risk, and to assess the modifying effect of body mass index (BMI). Long-term (≥10 years) use of ET, sequential EPT with <10 days per month progestin, and continuous-combined EPT (≥25 days/month progestin) were all associated with an elevated risk of endometrial cancer (OR, 4.5; 95% CI, 2.5-8.1; OR, 4.4; 95% CI, 1.7-11.2; and OR, 2.1; 95% CI, 1.3-3.3, respectively; all Ptrend < 0.001). The risk associated with short-term use was elevated only for ET preparations. The association for continuous-combined EPT was confined to thinner women (BMI, <25 kg/m2; Pinteraction = 0.03). Among heavier women (BMI, ≥25 kg/m2), use of continuous-combined EPT was associated with a statistically nonsignificant reduction in risk. These findings confirm that long-term use of ET, sequential EPT, or, among normal weight women, continuous-combined EPT is associated with increased risk of endometrial cancer. Cancer Epidemiol Biomarkers Prev; 19(2); 475–83
Clinical Presentation of Endometrioid Epithelial Ovarian Cancer with Concurrent Endometriosis: A Multicenter Retrospective Study
Authors: Lim Myong Cheol , Chun Kyoung-Chul , Shin So-Jin , Lee In Ho , Lim Kyung Taek , Cho Chi Heum , Park Sang-Yoon , Nam Joo-Hyun
Published: February 2010

Background: Endometrioid epithelial ovarian cancer (EEOC) is frequently diagnosed in conjunction with endometriosis and is suggested to arise during the process of endometriosis. This study evaluates the clinical manifestations, including endometriosis-related symptoms and their relationships according to the coexistence of endometriosis.

Methods: Using medical records, a retrospective analysis was conducted on 221 patients treated for EEOC at four tertiary educational hospitals between 2000 and 2008. The initial presenting symptoms, particularly those related to endometriosis, were examined in relation to the coexistence of endometriosis or other clinical variables.

Results: Endometriosis was identified in 82 (37.1%) of the 221 patients with EEOC. The most common symptoms were pelvic pain followed by gastrointestinal symptoms, palpable mass, abdominal distension, vaginal bleeding, and newly developed or exacerbated dysmenorrhea (18.1%) and dyspareunia (13.6%). Notably, dysmenorrhea and dyspareunia were frequently observed in patients with endometriosis. Among 210 patients identified with pretreatment serum CA-125, 54 (25.7%) displayed normal CA-125 levels (<35 units/mL) and 23.3% and 29.9% of patients without and with endometriosis had normal CA-125 levels, respectively (P = 0.381). Additionally, 32.6% of the patients with early-stage EEOC displayed normal CA-125 levels.

Conclusions: In this large series of patients with EEOC, the main presenting symptoms were pelvic pain followed by gastrointestinal symptoms, palpable mass, abdominal distension, vaginal bleeding, and newly developed or exacerbated dysmenorrhea and dyspareunia. Dyspareunia and dysmenorrhea were more frequently detected in patients with endometriosis. Normal CA-125 levels cannot be applied as a marker to exclude EEOC, particularly at the early stages. Cancer Epidemiol Biomarkers Prev; 19(2); 398–404
The Association of Metabolic Syndrome and Its Components with Serum Prostate-Specific Antigen Levels in a Korean-Screened Population
Authors: Jeong In Gab , Hwang Seung Sik , Kim Hong Kyu , Ahn Hanjong , Kim Choung-Soo
Published: February 2010

Background: Metabolic syndrome plays a potential role in the etiology of prostate cancer and is associated with the increase in prostatic growth rate in patients with benign prostatic hyperplasia. However, the influence of metabolic syndrome on prostate-specific antigen (PSA) level remains unclear.

Methods: Data were obtained from 23,601 men ages 40 years or older without a history of prostate cancer who underwent general health screening tests between 2006 and 2007 at Asan Medical Center. The criteria for metabolic syndrome were consistent with those defined by the NCEP-ATPIII-AHA/NHLBI statement. Multivariate linear regression analysis was used to determine the independent effects of age, body mass index (BMI), metabolic syndrome, and each component of metabolic syndrome, on PSA level.

Results: Geometric mean PSA level increased linearly and significantly with increasing age and decreasing BMI (P < 0.001). Although the geometric mean PSA levels were lower in men with metabolic syndrome than in those without the condition, metabolic syndrome no longer retained a statistically significant association with PSA after the adjustment for age and BMI (P = 0.850). Among five metabolic components, higher waist circumference and fasting plasma glucose level were significantly associated with lower PSA (P = 0.021 and P = 0.001), whereas hypertension was significantly associated with higher PSA (P < 0.001), after complete adjustment for age, BMI, and other metabolic components.

Conclusions: In our screened population, metabolic syndrome was not associated with PSA level. The lack of association between metabolic syndrome and PSA level may reflect the heterogeneous relationship between each metabolic risk factor and PSA level. Cancer Epidemiol Biomarkers Prev; 19(2); 371–80
Serum Vitamin D and Breast Density in Breast Cancer Survivors
Authors: Neuhouser Marian L. , Bernstein Leslie , Hollis Bruce W. , Xiao Liren , Ambs Anita , Baumgartner Kathy , Baumgartner Richard , McTiernan Anne , Ballard-Barbash Rachel
Published: February 2010

Background: Vitamin D influences cellular proliferation and proliferation-related breast tissue characteristics, such as mammographic breast density. Little is known about vitamin D status, assessed by serum 25-hydroxyvitamin D [25(OH)D], and its relationship to breast density in breast cancer survivors.

Methods: Participants were 426 postmenopausal breast cancer survivors from the Health, Eating, Activity, and Lifestyle Study. Women from New Mexico, Los Angeles, and western Washington were enrolled postdiagnosis. Data for this report are from an examination conducted 24 months postenrollment. Participants completed health-related questionnaires, gave fasting blood samples, and completed height and weight measurements. Serum [25(OH)D] was assayed by radioimmunoabsorbant assay. Breast dense area and percent density were measured from postdiagnosis-digitized mammograms. Multivariate linear regression tested associations of serum [25(OH)D] with mammographic breast density measures.

Results: Of the 426 participants, 22.8% were African-American, 11.3% were Hispanic, and 62.8% were non-Hispanic white. We observed no associations of serum [25(OH)D] with either breast density or breast dense area. Among women with vitamin D deficiency (serum [25(OH)D], <16.0 ng/mL; n = 103), mean percent breast density was 8.0%, and among those with sufficient status (n = 99; serum [25(OH)D], ≥32.0 ng/mL), mean percent density was 8.5%. Breast dense area averaged 27.2 and 26.2 cm2 for women with vitamin D deficiency and sufficiency, respectively.

Conclusion: Data from this multiethnic cohort of breast cancer survivors do not support the hypothesis that serum vitamin D, [25(OH)D], is associated with breast density in cancer survivors. Cancer Epidemiol Biomarkers Prev; 19(2); 412–7
Plasma Levels of Acid-Labile Subunit, Free Insulin-Like Growth Factor-I, and Prostate Cancer Risk: A Prospective Study
Authors: Mucci Lorelei A. , Stark Jennifer R. , Pollak Michael N. , Li Haojie , Kurth Tobias , Stampfer Meir J. , Ma Jing
Published: February 2010

Background: The acid-labile subunit (ALS) acts in the insulin-like growth (IGF) system by binding circulating IGF-I in a ternary complex with binding protein (IGFBP)-3 to prevent IGF-I from crossing the endothelial barrier. Given the role of the IGF system in prostate cancer, ALS may influence carcinogenesis by modulating IGF-I levels or bioavailability.

Methods: We undertook a prospective study nested in the Physicians' Health Study to examine ALS, free IGF-I, and prostate cancer. We assayed circulating levels of ALS and IGF components among 545 incident cases and 545 matched controls. We calculated relative risks (RR) and 95% confidence intervals (95% CI) adjusted for life-style factors, total IGF-I, and IGFBP3.

Results: ALS was positively correlated with total IGF-I (r = 0.58), IGFBP3 (r = 0.68), and free IGF-I (r = 0.36). Comparing highest versus lowest quartiles, we found no association between free IGF-I and prostate cancer risk (RR, 0.9; 95% CI, 0.6-1.3). In contrast, ALS was positively associated with risk among men in the 2nd (RR, 1.5; 94% CI, 1.0-2.3), 3rd (RR, 1.6; 94% CI, 1.1-2.5), and 4th quartiles (RR, 1.4; 94% CI, 0.9-2.1) compared with lowest quartile. The association was stronger for advanced stage tumors (RR, 2.0; 94% CI, 0.8-4.6). There was a suggestion of an interaction between ALS and total IGF-I, whereby high circulating IGF-I was associated with an increased risk of advanced prostate cancer among men with low but not higher ALS levels.

Discussion: Plasma ALS is positively associated with prostate cancer risk, and may interact biologically with IGF-I to affect carcinogenesis. These data provide further support for the role of the IGF axis in prostate cancer. Cancer Epidemiol Biomarkers Prev; 19(2); 484–91
Polymorphism in the GALNT1 Gene and Epithelial Ovarian Cancer in Non-Hispanic White Women: The Ovarian Cancer Association Consortium
Authors: Phelan Catherine M. , Tsai Ya-Yu , Goode Ellen L. , Vierkant Robert A. , Fridley Brooke L. , Beesley Jonathan , Chen Xiao Qing , Webb Penelope M. , Chanock Stephen , Cramer Daniel W. , Moysich Kirsten , Edwards Robert P. , Chang-Claude Jenny , Garcia-Closas Montserrat , Yang Hannah , Wang-Gohrke Shan , Hein Rebecca , Green Adele C. , Lissowska Jolanta , Carney Michael E. , Lurie Galina , Wilkens Lynne R. , Ness Roberta B. , Pearce Celeste Leigh , Wu Anna H. , Van Den Berg David J. , Stram Daniel O. , Terry Kathryn L. , Whiteman David C. , Whittemore Alice S. , DiCioccio Richard A. , McGuire Valerie , Doherty Jennifer A. , Rossing Mary Anne , Anton-Culver Hoda , Ziogas Argyrios , Hogdall Claus , Hogdall Estrid , Krüger Kjaer Susanne , Blaakaer Jan , Quaye Lydia , Ramus Susan J. , Jacobs Ian , Song Honglin , Pharoah Paul D.P. , Iversen Edwin S. , Marks Jeffrey R. , Pike Malcolm C. , Gayther Simon A. , Cunningham Julie M. , Goodman Marc T. , Schildkraut Joellen M. , Chenevix-Trench Georgia , Berchuck Andrew , Sellers Thomas A. ,   on behalf of the Ovarian Cancer Association Consortium, Australian Cancer Study (Ovarian Cancer),   Australian Ovarian Cancer Study Group
Published: February 2010

Aberrant glycosylation is a well-described hallmark of cancer. In a previous ovarian cancer case control study that examined polymorphisms in 26 glycosylation-associated genes, we found strong statistical evidence (P = 0.00017) that women who inherited two copies of a single-nucleotide polymorphism in the UDP-N-acetylgalactosamine:polypeptide N-acetylgalactosaminyltransferase, GALNT1, had decreased ovarian cancer risk. The current study attempted to replicate this observation. The GALNT1 single-nucleotide polymorphism rs17647532 was genotyped in 6,965 cases and 8,377 controls from 14 studies forming the Ovarian Cancer Association Consortium. The fixed effects estimate per rs17647532 allele was null (odds ratio, 0.99; 95% confidence interval, 0.92-1.07). When a recessive model was fit, the results were unchanged. Test for hetero geneity of the odds ratios revealed consistency across the 14 replication sites but significant differences compared with the original study population (P = 0.03). This study underscores the need for replication of putative findings in genetic association studies. Cancer Epidemiol Biomarkers Prev; 19(2); 600–4
Longer Relative Telomere Length in Blood from Women with Sporadic and Familial Breast Cancer Compared with Healthy Controls
Authors: Gramatges Maria M. , Telli Melinda L. , Balise Raymond , Ford James M.
Published: February 2010

Telomeres cap the ends of chromosomes and are composed of a series of noncoding hexamer repeats. Telomeres protect the integrity of DNA coding sequences and are integral to the maintenance of genomic stability. Previous studies have shown an association between shortened lymphocyte telomeres and increased risk for specific cancers. However, the association between telomere length and breast cancer risk is less clear. We examined the relative telomere length (RTL) in blood from women with no personal or family history of cancer (controls) compared with different populations of women with breast cancer and women at high genetic risk for developing breast cancer. RTL was determined as the telomere to single gene copy number ratio assessed by quantitative PCR. Breast cancer cases (low risk, n = 40; high risk, n = 62) had significantly longer RTL compared with unaffected controls (n = 50; mean RTL = 1.11 versus 0.84; P < 0.0001). The assessment of risk by RTL quartile showed an increased risk for breast cancer with each longer quartile, with the most significant risk observed in the longest quartile (odds ratio, 23.3; confidence interval, 4.4-122.3; P < 0.0003). Women without breast cancer but at high risk due to family history (n = 30) also showed longer telomeres than controls (mean RTL = 1.09 versus 0.84; P < 0.0001). Our analysis supports previous findings of longer RTL in breast cancer cases compared with controls, and is the first to observe longer RTL in women without breast cancer identified as high risk based on family history. Cancer Epidemiol Biomarkers Prev; 19(2); 605–13
Associations between Polymorphisms in Glucuronidation and Sulfation Enzymes and Mammographic Breast Density in Premenopausal Women in the United States
Authors: Yong Mellissa , Schwartz Stephen M. , Atkinson Charlotte , Makar Karen W. , Thomas Sushma S. , Newton Katherine M. , Aiello Bowles Erin J. , Holt Victoria L. , Leisenring Wendy M. , Lampe Johanna W.
Published: February 2010

Objective: Sex hormones are metabolized to less active compounds via (a) glucuronidation catalyzed by UDP-glucuronosyltransferases (UGT) and (b) sulfation catalyzed by sulfotransferases (SULT). Functional UGT and SULT polymorphisms can affect clearance of sex hormones, thereby influencing exposure in hormone-sensitive tissues, such as the breast. We assessed relationships between functional polymorphisms in the UGT and SULT genes and breast density in premenopausal women.

Methods: One hundred seventy-five women ages 40 to 45 years, who had a screening mammogram taken within the previous year, provided a genomic DNA sample. Mammograms were digitized to obtain breast density measures. Using generalized linear regression, we assessed associations between percent breast density and polymorphisms in the UGT1A and UGT2B families, SULT1A1, and SULT1E1.

Results: Women with the SULT1A1(H213/H213) genotype had 16% lower percent breast density compared with women with the SULT1A1(R213/R213) genotype after controlling for ethnicity (P = 0.001). Breast density was 5% lower among women carrying at least one copy of the UGT1A1(TA7)-UGT1A3(R11)-UGT1A3(A47) haplotype compared with the UGT1A1(TA6)-UGT1A3(W11R)-UGT1A3(V47A) haplotype (P = 0.07). No associations were observed between polymorphisms in the UGT2B family or SULT1E1 and breast density.

Conclusion: Polymorphisms in SULT1A1 and the UGT1A locus may influence percent breast density in premenopausal women. Cancer Epidemiol Biomarkers Prev; 19(2); 537–46
210Pb: A Predictive Biomarker of Retrospective Cigarette Smoke Exposure
Authors: Schayer Stephen R. , Qu Qingshan , Wang Yanling , Cohen Beverly S.
Published: February 2010

Although cigarette smoking continues to occur worldwide, there are few methods available to assess a person's retrospective exposure to mainstream smoke. The tobacco of cigarettes contains trace quantities of radioactive 210Pb and 210Po, which are volatilized and inhaled when a cigarette is smoked. It was hypothesized that urinary 210Pb and 210Po activity concentrations could be used as biomarkers of exposure to mainstream tobacco smoke. Human subjects (n = 250) were recruited from Beijing, China, and reported their smoking habits. Each subject provided a 24-hour urine sample, which was assayed for its 210Pb and 210Po activity concentrations. Although the urinary 210Po activity from smoking was very low compared with background levels, the urinary 210Pb activity correlated with the number of cigarettes smoked per day (CPD; ρ = 0.38, P < 0.001) and the urinary cotinine concentration (ρ = 0.52, P < 0.001). In a linear regression model, a 1-unit increase in CPD was associated with an increase of 0.13 mBq in urinary 210Pb activity. In a logistic regression model, a 1-unit increase in urinary 210Pb activity was associated with an estimated 25% increase in the odds of being a smoker. These data were modeled using the respiratory, gastrointestinal, and biokinetic models of the International Commission on Radiological Protection. When the final model was applied for a long-term smoker (20 CPD) that suddenly quits, the predicted urinary activity decreased to 50% of the steady-state activity in about 90 days. Based on this half-time estimate and the regression results, urinary 210Pb can be used to assess the probability of having smoked in the past months. Cancer Epidemiol Biomarkers Prev; 19(2); 338–50
Low Proportion of False-Negative Smears in the Finnish Program for Cervical Cancer Screening
Authors: Lönnberg Stefan , Anttila Ahti , Kotaniemi-Talonen Laura , Kujari Harry , Melkko Jukka , Granroth Gustav , Vornanen Martine , Pietiläinen Timo , Sankila Anna , Arola Johanna , Luostarinen Tapio , Nieminen Pekka
Published: February 2010

Background: We assessed the performance and validity of cytology in the Finnish screening program by considering high-grade neoplasia and cervical cancer (CIN3+) rates as detected in the program and by reevaluating cases observed after a negative screening test.

Methods: This retrospective study included 915 screen-detected CIN3+ cases and 421 cases observed after a negative screen. Randomized and blinded reevaluation of potential false-negative screening tests covered 345 archival case smears from women without a referral to colposcopy, as well as 689 control smears for estimating performance and validity measures.

Results: The false-negative rate at the cutoff of low-grade squamous intraepithelial lesion or worse was 35% (95% confidence interval, 30-40%). In the subpopulation with original screening result of Pap I, the false-negative rate was 23% (18-28%). Sensitivity of screening laboratory rereading for detecting low-grade lesions or worse as atypical was 75% (67-82%) and specificity 93% (91-94%). Reproducibility of specific cytologic diagnoses was only fair. False negatives constituted 11% of all CIN3+ diagnoses in the screened population; those false negatives with an original Pap I screening result constituted 5%.

Conclusions: Although screen failures in the form of diagnostic false negatives occur within the Finnish screening program, their effect on cancer incidence is fairly small and cannot be readily decreased without sacrificing the high specificity of screening or without high incremental costs. Feedback for the screening laboratories is needed, however, to improve the reproducibility of cytologic diagnoses to optimize the burden of intensified follow-up and treatment of precancerous lesions. Cancer Epidemiol Biomarkers Prev; 19(2); 381–7
Screen-Film Mammographic Density and Breast Cancer Risk: A Comparison of the Volumetric Standard Mammogram Form and the Interactive Threshold Measurement Methods
Authors: Aitken Zoe , McCormack Valerie A. , Highnam Ralph P. , Martin Lisa , Gunasekara Anoma , Melnichouk Olga , Mawdsley Gord , Peressotti Chris , Yaffe Martin , Boyd Norman F. , dos Santos Silva Isabel
Published: February 2010

Background: Mammographic density is a strong risk factor for breast cancer, usually measured by an area-based threshold method that dichotomizes the breast area on a mammogram into dense and nondense regions. Volumetric methods of breast density measurement, such as the fully automated standard mammogram form (SMF) method that estimates the volume of dense and total breast tissue, may provide a more accurate density measurement and improve risk prediction.

Methods: In 2000-2003, a case-control study was conducted of 367 newly confirmed breast cancer cases and 661 age-matched breast cancer-free controls who underwent screen-film mammography at several centers in Toronto, Canada. Conditional logistic regression was used to estimate odds ratios of breast cancer associated with categories of mammographic density, measured with both the threshold and the SMF (version 2.2β) methods, adjusting for breast cancer risk factors.

Results: Median percent density was higher in cases than in controls for the threshold method (31% versus 27%) but not for the SMF method. Higher correlations were observed between SMF and threshold measurements for breast volume/area (Spearman correlation coefficient = 0.95) than for percent density (0.68) or for absolute density (0.36). After adjustment for breast cancer risk factors, odds ratios of breast cancer in the highest compared with the lowest quintile of percent density were 2.19 (95% confidence interval, 1.28-3.72; Pt <0.01) for the threshold method and 1.27 (95% confidence interval, 0.79-2.04; Pt = 0.32) for the SMF method.

Conclusion: Threshold percent density is a stronger predictor of breast cancer risk than the SMF version 2.2β method in digitized images. Cancer Epidemiol Biomarkers Prev; 19(2); 418–28
Association of Alcohol Intake with the Risk of Malignant Lymphoma and Plasma Cell Myeloma in Japanese: A Population-Based Cohort Study (Japan Public Health Center–based Prospective Study)
Authors: Kanda Junya , Matsuo Keitaro , Inoue Manami , Iwasaki Motoki , Sawada Norie , Shimazu Taichi , Yamaji Taiki , Sasazuki Shizuka , Tsugane Shoichiro ,   Japan Public Health Center–based Prospective Study Group
Published: February 2010

Few studies have evaluated the association between alcohol intake and the risk of the lymphoid neoplasms malignant lymphoma (ML) and plasma cell myeloma (PCM) among Asian populations. We conducted a large-scale population-based cohort study of 95,520 Japanese subjects (45,453 men and 50,067 women; age 40-69 years at baseline) with an average 13 years of follow-up, during which a total of 257 cases of ML and 89 of PCM were identified. Hazard ratios and 95% confidence intervals were estimated using a Cox regression model adjusted for potential confounders. Alcohol intake of ≥300 g/week was associated with a significantly lower risk of lymphoid neoplasms (hazard ratio, 0.60; 95% confidence interval, 0.37-0.98) than occasional drinking at a frequency of <1 day/month, and the trend for alcohol consumption was significant (P = 0.028). A similar trend was observed for the subcategories of ML, PCM, and non–Hodgkin lymphoma (NHL), albeit that the results were significant only for alcohol consumption at ≥300 g/week in NHL patients, probably due to the small number of subjects in each category. In conclusion, we found that alcohol had an inverse association with the risk of lymphoid neoplasms, particularly the risk of NHL, among a Japanese population. Cancer Epidemiol Biomarkers Prev; 19(2); 429–34
Intestinal Protozoa Infections among Patients with Ulcerative Colitis: Prevalence and Impact on Clinical Disease Course
Authors: Yamamoto-Furusho Jesús K. , Torijano-Carrera Emma
Published: February 2010

Background: Epidemiological and microbiologic studies suggest that enteropathogenic microorganisms play a substantial role in the clinical initiation and relapses of inflammatory bowel disease. Aim: To explore the prevalence of intestinal protozoa in patients with ulcerative colitis (UC) and its impact on clinical disease course. Methods: A total of 215 patients with definitive diagnosis of UC were studied. Fresh feces samples taken from all UC patients were examined immediately using trichrome-staining methods. Results: A total of 103 female and 112 male UC patients were analyzed. The mean age at diagnosis was 30.5 ± 10.8 years. The prevalence of overall parasitic infections was 24% and distributed as follows: Blastocystis hominis in 22 patients (10%), Endolimax nana in 19 cases (9%), and Entamoebahistolytica in 11 cases (5%). A significantly increased frequency of protozoa infection was found in those patients with persistent activity and intermittent activity as compared to active than inactive group (p = 1 × 10–7, OR 13.05, 95% CI 4.28–42.56, and p = 0.003, OR 1.42–14.47, respectively). Interestingly, this association remained significant when we compared the persistent activity group versus intermittent activity group (p = 0.003, OR 2.97, 95% CI 1.35–6.59). Subgroup analysis showed no association between protozoa infection (E. histolytica, B. hominis, and E. nana) and other clinical variables such as gender, extent of disease, extraintestinal complications, medical treatment and grade of disease activity. Conclusion: The prevalence of intestinal protozoa infections in Mexican UC patients was 24% and these microorganisms could be a contributing cause of persistent activity despite medical treatment in our population.
Origin, Development and Regulation of Human Leydig Cells
Authors: Svechnikov K. , Landreh L. , Weisser J. , Izzo G. , Colón E. , Svechnikova I. , Söder O.
Published: February 2010

Sex steroids are crucial regulators of sexual differentiation and the proper development of secondary sex characteristics and patterns of sexual behavior. Since Leydig cells are the primary major producers of these steroid hormones, maintenance of the normal functions of these cells determines the reproductive capacity and fertility of males. The present minireview discusses recent findings concerning endocrine and paracrine regulation of the proliferation, differentiation and involution of human Leydig cells. The physiology and function of the two distinct fetal and adult populations of human Leydig cells are described, with particular focus on the paracrine environment that triggers their differentiation and functional maturation. The roles of established and more recently discovered paracrine regulators of this maturation, including insulin-like factor 3, platelet-derived growth factor-α, desert hedgehog, ghrelin and leptin are considered. A brief description of the origin, ontogenesis and functional markers of human fetal and adult Leydig cells is presented.
Screening Markers of Impaired Glucose Tolerance in the Obese Pediatric Population
Authors: Tsay J. , Pomeranz C. , Hassoun A. , Zandieh S.O. , Rutledge J. , Vogiatzi M.G. , Oberfield S.E. , Motaghedi R.
Published: February 2010

Background: With the epidemic of childhood obesity, it is crucial to devise a simple screening protocol to predict impaired glucose tolerance (IGT) or pre-diabetes. The oral glucose tolerance test (OGTT), which is the gold standard for the diagnosis of IGT, is impractical for screening purposes. This pilot study was designed to formulate a simple, sensitive algorithm to predict IGT using clinical and laboratory parameters. Methods: Ethnicity, family history of diabetes, pubertal status, BMI z-score, blood pressure, lipids, hemoglobin A1c (HbA1c) and OGTT data were retrospectively collected from 209 overweight multi-ethnic subjects aged 3–21 years. Multivariate logistic regression was used to determine independent predictors of IGT. Results: HbA1c was the only significant predictor of IGT (p = 0.001), whereas fasting glucose was not. A cut-off of 5.5% had the best combined sensitivity (85.7%) and specificity (56.9%) with an odds ratio of 7.9 of having IGT when HbA1c is ≧5.5%. The remaining clinical parameters were not significant predictors of IGT. Conclusion: While fasting blood glucose does not seem to be a predictor of IGT, we propose that HbA1c ≧5.5% can be used as a screening test to assess the risk of IGT and to determine who should undergo diagnostic OGTT. Large prospective studies validating our findings are warranted.
Familial Isolated Primary Pigmented Nodular Adrenocortical Disease Associated with a Novel Low Penetrance PRKAR1A Gene Splice Site Mutation
Authors: Storr Helen L. , Metherell Louise A. , Dias Renuka , Savage Martin O. , Rasmussen Åse K. , Clark Adrian J.L. , Main Katharina M.
Published: February 2010

Background/Aims: Primary pigmented nodular adrenocortical disease (PPNAD) is associated with inactivating germline protein kinase A regulatory subunit type 1-α (PRKAR1A) mutations and loss of heterozygosity at the 17q22–24 locus in approximately 50% patients. PRKAR1A mutations are observed in both isolated PPNAD (iPPNAD) and Carney complex (CNC). Most mutations result in a functionally null-allele and exhibit high penetrance. We genotyped members of an extended family for a novel PRKAR1A mutation and undertook detailed phenotyping for CNC in the affected individuals. Methods: A 10.5-year-old male was diagnosed with PPNAD; the patient’s mother also had iPPNAD. A 13-year-old sibling and 7 other relatives (mean age 58.2, range 29.1–80.2 years) were referred for PRKAR1A mutation analysis. Results: DNA analysis of the index case and parent revealed a novel germline heterozygous PRKAR1A mutation at the +1 position of the acceptor site of intron 3 [c.349 G>T]. The same heterozygous splice site mutation was present in the sibling with no PPNAD or CNC manifestations and 2 other individuals aged 54.9 and 57.1 years who had subclinical Cushing’s syndrome but no features of CNC. Conclusion: We conclude that c.349 G>T, a novel splice site germline PRKAR1A defect, has low penetrance resulting in incomplete clinical expression in this kindred.
SDHD-Related Chromaffin Tumours: Disease Localisation to Genetic Dysfunction
Authors: Srirangalingam U. , Khoo B. , Matson M. , Carpenter R. , Reznek R. , Maher E.R. , Chew S.L. , Drake W.M.
Published: February 2010

Background/Aims: To describe the management of a subject with multiple chromaffin tumours found to have a novel succinate dehydrogenase D (SDHD) mutation. Case: A 15-year-old boy with marked hypertension was found to have elevated urinary catecholamines and initial imaging thought to represent bilateral adrenal phaeochromocytomas. An adrenal venous catheter was required to clarify a right adrenal phaeochromocytoma and a left abdominal paraganglioma, distinct from the left adrenal gland. Excision of these tumours, with preservation of the left adrenal gland, provided a cure for this subject without the need for lifelong steroid replacement. Genetic analysis revealed a novel SDHD mutation (c. 169 + 1 G>A) which was shown to result in loss of the 5′ splice site and exclusion of exon 2 during splicing. This suggests the likely pathogenicity of this mutation. Disease surveillance in this subject and genetic screening of first degree relatives is ongoing. Conclusions: Genetic testing should be considered in all subjects presenting with a chromaffin tumour. In certain circumstances an adrenal venous sampling catheter for catecholamines may clarify diagnostic uncertainty. The complex management issues raised in the care of these subjects requires the involvement of a multidisciplinary team with the relevant expertise.
Inhibitory Effect of Paclitaxel on Endothelial Cell Adhesion and Migration
Authors: Li Hua , Zhang Li-jun , Chen Bai-hua , Zhou Xuan , Su Ke , Shi Wen-tao , Wu Jun-zhu , Yu Hong , Wei Lei
Published: February 2010

The long-term success of percutaneous coronary interventions has been limited by restenosis. Therefore, local delivery of paclitaxel, an antiproliferative agent, using drug-eluting stents has been applied to prevent in-stent restenosis. However, paclitaxel not only inhibits smooth muscle cell proliferation, but also delays re-endothelialization of the damaged site, which may cause potentially life-threatening cardiovascular adverse events, especially late and very late stent thrombosis. We investigated the role of paclitaxel in endothelial cell line ECV304 adhesion and migration. Accordingly, changes in vasodilator-stimulated phosphoprotein protein (VASP) phosphorylation and cAMP-dependent protein kinase activity during ECV304 cell detachment and reattachment were investigated as well. The results showed that the decrease in VASP phosphorylation paralleled the inhibition of cAMP-dependent protein kinase (PKA) activity in the presence of paclitaxel (10 µg/l). Cell adhesion assay and two- and three-dimensional cell migration assays were performed to determine the effect of paclitaxel on the adhesion and migration of ECV304 cells. Paclitaxel significantly suppresses the adhesion (p < 0.05) and migration of ECV304 cells (p < 0.05). These data suggest that the inhibitory effect of paclitaxel may be produced by decreasing the phosphorylation of VASP via inhibition of PKA activity during ECV304 cell adhesion and migration.
Insulin Inhibits and Oral Sucrose Increases Neointimal Growth after Arterial Injury in Rats
Authors: Breen Danna M. , Dhaliwall Jiwanjeet K. , Chan Kalam K. , Guo June , Lam Loretta , Bendeck Michelle P. , Giacca Adria
Published: February 2010

Background/Aims: In our previous studies, rats on insulin treatment (5 U/day) and oral glucose to avoid hypoglycemia had reduced neointimal growth after arterial injury. However, plasma glucose in the insulin-treated rats was lower than normal and the effect of oral glucose remained undetermined. In this study, the effects of normoglycemic hyperinsulinemia and oral glucose or sucrose were investigated in the same model. Methods: Rats were divided into 6 groups: (1) control implants and tap water; (2) insulin implants (5 U/day) and oral glucose + i.p. glucose to avoid any glucose lowering; (3) insulin implants (4 U/day) and oral glucose; (4) insulin implants (4 U/day) and oral sucrose; (5) control implants and oral glucose, and (6) control implants and oral sucrose. Results: Insulin treatment at both doses reduced neointimal area (p < 0.001) 14 days after injury in rats receiving oral glucose but not in those receiving oral sucrose. Oral glucose, without insulin, had no effect on neointimal formation, whereas oral sucrose increased neointimal growth (p < 0.05). Oral sucrose (p < 0.05) but not oral glucose decreased insulin sensitivity measured with hyperinsulinemic clamps. Conclusions: (1) Insulin decreases neointimal growth after arterial injury independent of glucose-lowering or oral glucose administration and (2) oral sucrose per se affects neointimal growth.
Enhanced Matrix Metalloproteinase Activity in the Spontaneously Hypertensive Rat: VEGFR-2 Cleavage, Endothelial Apoptosis, and Capillary Rarefaction
Authors: Tran Edward D. , DeLano Frank A. , Schmid-Schönbein Geert W.
Published: February 2010

Besides an elevated blood pressure, the spontaneously hypertensive rat (SHR) has multiple microvascular complications including endothelial apoptosis with capillary rarefaction. The SHR also has elevated levels of proteolytic (e.g. matrix metalloproteinase, MMP) activity and apoptosis in microvascular cells compared to its normotensive control, but the specific enzymes involved and the molecular mechanism for apoptosis are unknown. We hypothesize that selected MMPs cleave the extracellular domain of vascular endothelial growth factor receptor-2 (VEGFR-2), which in turn causes endothelial apoptosis and capillary rarefaction. Zymographic analysis shows that gelatinase (MMP-2 and MMP-9) and matrilysin (MMP-7) activities are significantly enhanced in SHR plasma. The SHR has lower levels of the extracellular domains of VEGFR-2 in cardiac microvessels. Furthermore, application of plasma from the SHR, or purified MMP-9 and MMP-7 to naïve cells causes cleavage of the extracellular domain of VEGFR-2. The receptor cleavage was blocked by broad-acting MMP inhibitors (GM6001 1 µM, EDTA 10 mM, or doxycycline 11.3 µM). Chronic MMP inhibition (doxycycline, 5.4 mg/kg/day, 24 weeks) attenuated VEGFR-2 cleavage, endothelial apoptosis, and capillary rarefaction in the SHR. These results suggest elevated plasma MMP activities may cleave VEGFR-2, resulting in endothelial apoptosis and capillary rarefaction in the SHR.
Mechanical Stress Modulates SOCS-1 Expression in Human Vascular Smooth Muscle Cells
Authors: Dangers Marc , Kiyan Julia , Grote Karsten , Schieffer Bernhard , Haller Hermann , Dumler Inna
Published: February 2010

Background: The growth-promoting effect of mechanical stress on vascular smooth muscle cells (VSMC) has been implicated in the progress of cardiovascular diseases related to elevated blood pressure. The underlying molecular mechanisms are, however, not completely defined. Methods: We have studied primary human aortic VSMC using a model for multilateral stretch. Expression of the suppressor of cytokine signaling (SOCS) family member SOCS-1 and related molecular mechanisms were studied using TaqMan analysis, immunoblotting, protein silencing, specific cell treatment, immunoprecipitation and immunocytochemistry. Results: Mechanical stretch inhibits SOCS-1 mRNA and protein expression. This effect was abolished by cell treatment with methyl-β-cyclodextrin disrupting lipid rafts and with RGD peptide affecting integrins. Inhibition of integrin interaction with another cellular receptor, urokinase receptor (uPAR), as well as uPAR silencing also abolished stretch-induced SOCS-1 downregulation. Mechanical stretch resulted in uPAR redistribution to lipid rafts and in its colocalization with focal adhesion kinase (FAK). Stretch impairs polyubiquitination and proteosomal degradation of FAK leading to FAK upregulation in stretched VSMC. SOCS-1 silencing and inhibition of proteosomal degradation simulate this effect. Conclusion: Our study identifies SOCS-1 as a novel participant involved in the propagation of mechanical stimuli in human VSMC, which might be relevant for the development of cardiovascular diseases.
Housing et santé mentale
Authors: Leroy Claude
Published: February 2010

From several field studies, the author has endeavored to specify the relationships between the territory of human city dwellers, their self-images and those of others. When certain conditions are not met, various mental illnesses arise. The reason is that in the territorial-spatial arrangement the needs to consider the complexity of urban living and the sectioning plans are governed by financial decisions. What has been saved by financial planning in city management appears to be a rather excessive price to pay for health and welfare.
Sozialer Wandel und seelische Gesundheit
Authors: Guntern G.
Published: February 2010

The economic development and the resulting mass tourism since the Second World War have provoked in the whole alpine region an economic and a social change of considerable importance. The qualitative and quantitative aspects of this process should be of interest to the social sciences in general, and to social psychiatry in particular. The paper presented here deals with some results from a sociological-sociopsychiatric longitudinal study of socio-cultural change. The object of this longitudinal study is a mountain village in the alps which shortly after the construction of a road communication became a famous tourist station of world-wide renown. The study tries to examine the mountain village as a paradigma of the social change and the following psychological, psychosomatic and psychosocial difficulties of adaptation during the period of the so-called ‘cultural lag’. The factors and the manifestations, the actors and the consequences of the social change have been discussed. The economic change has altered the roles, the distribution of work, the culturally determined and traditionally learned patterns of behaviour, and the underlying pattern of values and normative attitudes. This change functions as a stressor and the individuals affected by this change are undergoing stress reactions. The most important parameters of this general stress and of the phenomena of inadequate adaptation to the social change are the raised consumation of alcohol, drugs and tobacco, and the psychosomatic and sexual behaviour disorders. How strong the correlations and interdependences between social change, stress and disorders of adaptation really are, cannot yet be shown in this study. Further data and information needs to be gathered during the longitudinal study to verify or to falsify the above-mentioned hypotheses.
Der Dermatozoenwahn
Authors: Ganner H.G. , Lorenzi E.
Published: February 2010

Delusion of skin-parasitosis is a very characteristic disorder, and it can appear as an independent syndrome or as a concomitant phenomenon of other psychiatric illnesses. Like most delusional formations it can also be induced and appear as a symbiontic psychosis; the involutional age seems to be an essential precondition for this psychopathological phenomenon.
Der prognostische und therapeutische Aspekt katathymer Wahnbildungen
Authors: Gabriel E.
Published: February 2010

The prognostic and therapeutic aspects of catathymic delusional formations, excluding those associated with organic psychoses, are comprehensively presented from five points of view: (1) the present possibilities of psychiatric prognostication; (2) prognostic implications of nosological classifications; (3) prognostic significance of nosographic characteristics; (4) relationship to general rules of psychiatric prognostics; (5) therapeutic points. Under (3) we report our own findings concerning the long-term development of delusional formations and the long-term course of delusional illnesses classified as ‘schizophrenia of late onset’; we report their relationships to the formation of defect syndromes and to the psycho-organic deterioration in old age.
Zur Wahnwahrnehmung – Versuch der Begriffsbestimmung und experimentelle Ergebnisse
Authors: Müller E. , Wytek R.
Published: February 2010

In order to circumscribe the concept of delusional perception as the essential element in the diagnosis of delusional states we have firstly reviewed the already well-known views in the literature. The results of two experimental psychological investigations are discussed, which are believed to underline the importance of perceptual disorders in patients with delusion.
Das nosologische Problem katathymer Wahnbildungen aus genetischem Aspekt
Authors: Gabriel E.
Published: February 2010

After pointing to the heterogeneous results of past investigations into the genetics of catathymic delusional illnesses we present our own findings. By grouping the primary probands according to their psychopathology we showed that the relatively few schizophrenic secondary probands are fairly equally distributed over all the subgroups of the case material, whereas the relatively frequent manic depressive secondary probands are related exclusively to those primary probands whose general psychiatric symptomatology, irrespective of the catathymic delusional syndrome, was classified psychopathologically as manic-depressive.
Transsexualism and Social Attitudes
Authors: Jonas Stanislaw P.
Published: February 2010

After a brief review of the literature, a case of a male-to-female transsexual, with a 4-year follow-up, is presented. The etiological factors and some social responses to this pathology are discussed.
EEG Examination during Delirium tremens
Authors: Allahyari H. , Deisenhammer E. , Weiser G.
Published: February 2010

In 30 male patients several EEG examinations could be carried out during delirium tremens (d.t.) or shortly thereafter. Most of the patients showed a normal EEG or changes which can be explained with regard to sedation through medication. 1 patient showed generalized paroxysmal spike wave bursts. On account of experimental results, we may assume that a transitory cerebral excitibality change occurs in d.t. This pathophysiological basis explains the normal EEGs and paroxysmal bursts during d.t. 4 cases showed passages of pronounced diffuse slow activity during d.t. partly accompanied by rhythmic bilateral slow waves. These changes point to a complication of d.t. that occurs because of another disease which results in cerebral functional disturbances as in other organic psychoses.
Die Genetik der Psychosen unter verändertem Aspekt
Authors: Lange Volkmar
Published: February 2010

To analyze the biological pathways of the genetical activity in psychoses is growing more and more to an important goal. The research in this field should be started on the assumption of a multifactorial hereditary system controlling the somatic base of mental illness in a specific way as can be argued from twin and family studies. Screening the present data, there is strong evidence that the metabolism of affective psychoses is characterized by quantitative deviations only concerning the 5-hydroxytryptamine and norepinephrine turnover particularly. The biochemical findings in schizophrenic psychoses are suspicious for qualitative abnormities too. There are some indications of toxic products in the catecholamine metabolism and of antibodies against brain substances. All these disturbances could be caused by structural gene mutants or by mutations of the genetical regulatory system changing the sensitivity for the environmental stimulus. The simultaneous investigation of simple inherited serum groups is described as a useful tool for biological marking of the responsible genotypes.