Association study of nicotinic acetylcholine receptor genes identifies a novel lung cancer susceptibility locus near CHRNA1 in African-Americans

Studies in European and East Asian populations have identified lung cancer susceptibility loci in nicotinic acetylcholine receptor (nAChR) genes on chromosome 15q25.1 which also appear to influence smoking behaviors. We sought to determine if genetic variation in nAChR genes influences lung cancer susceptibly in African-Americans, and evaluated the association of these cancer susceptibility loci with smoking behavior. A total of 1308 African-Americans with lung cancer and 1241 African-American controls from three centers were genotyped for 378 single nucleotide polymorphisms (SNPs) spanning the sixteen human nAChR genes. Associations between SNPs and the risk of lung cancer were estimated using logistic regression, adjusted for relevant covariates. Seven SNPs in three nAChR genes were significantly associated with lung cancer at a strict Bonferroni-corrected level, including a novel association on chromosome 2 near the promoter of CHRNA1 (rs3755486: OR = 1.40, 95% CI = 1.18-1.67, P = 1.0 × 10⁻⁴). Association analysis of an additional 305 imputed SNPs on 2q31.1 supported this association. Publicly available expression data demonstrated that the rs3755486 risk allele correlates with increased CHRNA1 gene expression. Additional SNP associations were observed on 15q25.1 in genes previously associated with lung cancer, including a missense variant in CHRNA5 (rs16969968: OR = 1.60, 95% CI = 1.27-2.01, P = 5.9 × 10⁻⁵). Risk alleles on 15q25.1 also correlated with an increased number of cigarettes smoked per day among the controls. These findings identify a novel lung cancer risk locus on 2q31.1 which correlates with CHRNA1 expression and replicate previous associations on 15q25.1 in African-Americans.     

CT colonography: Friend or foe of practicing endoscopists

AIM: To investigate the perceived impact of computed tomographic colonography (CTC) on endoscopists’ current and future practice.METHODS: A 21-question survey was mailed to 1570 randomly chosen American Society for Gastrointestinal Endoscopy (ASGE) members. Participants reported socio-demographics, colonoscopy volume, percentage of colonoscopies performed for screening, and likelihood of integration of CTC into their practice.RESULTS: A total of 367 ASGE members (23%) returned the questionnaire. Respondents were predominantly male (> 90%) and white (83%) with an average age of 49 years. Most respondents (58%) had no plans to incorporate CTC into daily practice and only 7% had already incorporated CTC into daily practice. Private practice respondents were the least likely to incorporate this modality into their daily practice (P = 0.047). Forty-three percent of participants were willing to take courses on CTC reading, particularly those with the highest volume of colonoscopy (P = 0.049). Forty percent of participants were unsure of CTC’s impact on future colonoscopy volume while 21% and 18% projected a decreased and increased volume, respectively. The estimated impact of CTC volume varied significantly by age (P = 0.002). Respondents > 60 years felt that CTC would increase colonoscopy, whereas those < 40 years thought CTC would ultimately decrease colonoscopy.CONCLUSION: Practicing endoscopists are not enthusiastic about the incorporation of CTC into their daily practice and are unsure of its future impact on their practice.     

End-of-dose wearing off in Parkinson disease: a 9-question survey assessment

We have previously reported that the use of a 32-symptom Wearing-off Questionnaire (WOQ-32) identified wearing off more frequently than a clinician's evaluation or the complications subscale of the Unified Parkinson Disease Rating Scale (UPDRS). However, this prototype tool was not designed for clinical practice and required simplification for daily use. Although wearing off is a commonly understood concept among neurologists caring for Parkinson disease patients, there are a number of definitions in the literature. For the purpose of this study and to include both motor and nonmotor parkinsonian symptoms, wearing off was defined as a generally predictable recurrence of motor and nonmotor symptoms that precedes scheduled doses of anti-parkinsonian medication and usually improves after those doses. Using this definition, retrospective analysis and expert opinion were used to identify the 9 most predictive and relevant of the symptoms previously identified as part of the WOQ-32. The resulting 9-symptom questionnaire (WOQ-9) identified 158 (95.8%) of the 165 subjects captured by the 32-Symptom Wearing-off Questionnaire as having wearing off, excluding 7 subjects reporting only balance difficulty (n = 3), numbness (n = 2), difficulty standing (n = 1), and abdominal discomfort (n = 1). Subjects reporting wearing off with the WOQ-9 were significantly younger, had been longer diagnosed with Parkinson disease, experienced a longer duration of levodopa therapy, exhibited a higher UPDRS total score, had higher levodopa equivalent dosages, and increased dyskinesia compared with patients not identified as wearing off with the WOQ-9. No statistical differences were noted with respect to sex, UPDRS subsection scores, Schwab & England Scale, or Hoehn & Yahr Scale.     

Cleavage of cystatin C in the cerebrospinal fluid of patients with multiple sclerosis

OBJECTIVE: The diagnosis of multiple sclerosis (MS) can be challenging because of the lack of a specific diagnostic test. Recent advances in proteomics, however, offer new opportunities for biomarker discovery and the study of disease pathogenesis. METHODS: We analyzed cerebrospinal fluid (CSF) samples from 29 patients with MS or clinically isolated syndromes (CIS), 27 patients with transverse myelitis (TM), 50 patients with human immunodeficiency virus (HIV) infection, and 27 patients with other neurological diseases (ONDs) by surface-enhanced laser desorption/ionization time-of-flight mass spectroscopy. RESULTS: We found a unique protein of 12.5 kDa that was 100% specific for MS/CIS compared with TM or OND. Low levels of this protein were found in some patients with HIV infection. Tandem mass spectroscopy of a tryptic digest of this 12.5 kDa protein identified it as a cleavage product of full-length cystatin C (13.4 kDa), an important inhibitor of cysteine proteases including the cathepsins. Although total cystatin C levels in the MS patients was not different compared with controls, the patients with the highest 12.5/13.4 peak ratios also had the greatest cathepsin B inhibitory activity. INTERPRETATION: This suggests that cleavage of cystatin C may be an adaptive host response and may identify a subgroup of patients with MS.     

Life stress,negative mood states,and antibodies to heat shock protein 70 in endometrial cancer

Heat shock protein 70 (HSP70), an intracellular chaperone “stress protein,” has been identified in the extracellular milieu, where it may exert regulatory effects upon monocytes. HSPs are overexpressed in many cancers and implicated in tumorigenesis. Few studies have examined the relationship between psychosocial factors and HSP levels, particularly in cancer. The purpose of the present study was to examine the relationship between negative psychosocial states (life events stress and negative mood states) and serum concentration of HSP70 antibodies among women with endometrial cancer, the fourth most common cancer among women in the United States. Thirty-six women scheduled to undergo surgery for suspected endometrial adenocarcinoma underwent a psychosocial assessment and peripheral venous blood draw. Life events stress was assessed using an abbreviated version of the Life Experiences Survey; negative mood states were assessed using abbreviated versions of the Structured Interview Guide for the Hamilton Anxiety and Depression Scales and the Profile of Mood States. HSP70 antibody levels were regressed sequentially on life events stress and negative mood variables while controlling for body mass index (BMI) and cancer stage. Results revealed that greater HSP70 antibody concentrations were associated with greater impact of recent negative life events (p = .04), anxious symptomatology (p = .007), depressive symptomatology (p = .03), and total mood disturbance (p = .001) after controlling for BMI and cancer stage. While based on a modest sample size, these preliminary results suggest that larger-scale research exploring the relationships among psychosocial factors and HSP70 in cancer patients may be warranted.     

Pure Natural Orifice Translumenal Endoscopic Surgery (NOTES) Transvaginal Nephrectomy

Natural orifice translumenal endoscopic surgery (NOTES) within urology has largely been limited to experimental animal studies and diagnostic procedures in humans. Attempts to complete a pure NOTES transvaginal nephrectomy have thus far been unsuccessful. We report the first clinical experience with pure NOTES transvaginal nephrectomy.