The Liminology of Oneida Lake - An Interim Report

This interim report discusses the general concepts of lake eutrophication and presents the findings of the first year of field investigations on the eutophication of Oneida Lake, New York. Routine biological and chemical data revealed that the lake has become eutrophic both through the natural processes of lake aging and from the inflow of nutrient-rich water from the fertile drainage basin. The four most important factors affecting the biological activities within the lake are: (1) the high fertility of the drainage basin, (2) the physical position and shallowness of the lake, (3) mixing of the water by wind action, and (4) the inclusion of bottom sediments in the recycling of nutrient materials

Effect of lifetime alcohol consumption on the histological severity of non‐alcoholic fatty liver disease

Background & Aims Non‐alcoholic fatty liver disease ( NAFLD ) is defined based on recent alcohol consumption; however, remote or lifetime alcohol consumption is not taken into account. It is not known whether lifetime alcohol consumption contributes to the severity of disease in patients with NAFLD . To determine the effect of lifetime alcohol consumption on the histological severity in patients with NAFLD . Patients & Methods Adults >18 years of age with presumed NAFLD and alcohol consumption <40 g/week were enrolled. Lifetime alcohol consumption was determined using a questionnaire. Patients with a history of long‐term alcohol abuse or dependence were excluded. A liver biopsy was reviewed by a single pathologist in a blinded fashion. Demographic, clinical and histological findings were compared in those who had regular alcohol consumption and those who did not. Results A total of 77 patients had fatty liver on biopsy. Fifty‐two patients had a history of regular alcohol consumption. The median lifetime cumulative alcohol intake was 24 gram‐years. On multivariable analysis, increasing age ( OR 1.07, 95% CI 1.01–1.14) was associated with severe liver disease, whereas alcohol consumption of ≥24 gram‐years was associated with less severe disease ( OR 0.26, 95% CI 0.07–0.97, P  = 0.04). Patients who continued to consume alcohol or had been abstinent for ≤1 year had less severe disease. Conclusion Some degree of regular alcohol consumption over the course of a lifetime compared to minimal intake appears to have a protective effect on the histological severity of liver disease among patients with strictly defined NAFLD .Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/102218/1/liv12230.pd

A Longitudinal Study of Attention-Deficit/Hyperactivity Disorder Symptoms in Preschool-Age Children

Attention-deficit hyperactivity disorder (ADHD) is among the most common reasons for referral to children\u27s mental health clinics, with an estimated prevalence of 3% to 5% in the general population of school-age children. Children who exhibit the requisite behaviors may obtain a diagnosis of ADHD at any age; however, symptom onset must occur before age 7 and persist for at least 6 months. Despite these temporal requirements for diagnosis, little empirical information about the manifestation and stability of ADHD symptoms in preschool children exists. This study provides information about the initial presence and stability over one academic year of ADHD behaviors in a sample of 290 preschool children rated by mothers and/or teachers. Data suggest higher levels of these behaviors at home versus school, with behaviors remaining stable over the course of the academic year at school, and diminishing over this time period at home. Family environment factors (e.g., socioeconomic status, family stress) were not found to have strong predictive relationships with levels of ADHD behaviors in this sample of preschoolers including little support for a directional relationship between dysfunctional parenting behaviors and child ADHD symptoms. Conclusions and clinical implications of these finding, are provided and may assist psychologists in their efforts to diagnose and treat this disorder in young children

Is it Crohn's disease? A severe systemic granulomatous reaction to sulfasalazine in patient with rheumatoid arthritis

Abstract Background Sulfasalazine is a widely used anti-inflammatory agent in the treatment of inflammatory bowel disease and several rheumatological disorders. Although as many as 20% of treated patients may experience reversible, dose-dependent side effects, less frequent but potentially severe, systemic reactions have also been reported. Case Presentation A severe systemic reaction to sulfasalazine developed in a 21-year old female with rheumatoid arthritis characterized by eosinophilia, granulomatous enteritis and myelotoxicity, cholestatic hepatitis, and seizures. The clinical course and management of this patient are presented as well as a review of the incidence and outcome of severe systemic reactions to sulfasalazine. Conclusions Granulomatous myelotoxicity and enteritis developed in a 21 year old female within 3 weeks of initiating sulfasalazine for rheumatoid arthritis. Following a short course of corticosteroids, the patient had resolution of her cholestatic hepatitis, rash, eosinophilia, and gastrointestinal symptoms with no residual manifestations at 7 months follow-up. Although severe reactions to sulfasalazine are rare and unpredictable, practicing physicians should be aware of unusual clinical presentations of toxicity when prescribing sulfasalazine.http://deepblue.lib.umich.edu/bitstream/2027.42/112406/1/12876_2001_Article_8.pd

Ethanol and Acetaminophen Synergistically Induce Hepatic Aggregation and TCH346-Insensitive Nuclear Translocation of GAPDH

The glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) signals during cellular stress via several post-translational modifications that change its folding properties, protein-protein interactions and sub-cellular localization. We examined GAPDH properties in acute mouse liver injury due to ethanol and/or acetaminophen (APAP) treatment. Synergistic robust and time-dependent nuclear accumulation and aggregation of GAPDH were observed only in combined, but not individual, ethanol/APAP treatments. The small molecule GAPDH-targeting compound TCH346 partially attenuated liver damage possibly via mitochondrial mechanisms, and independent of nuclear accumulation and aggregation of GAPDH. These findings provide a novel potential mechanism for hepatotoxicity caused by combined alcohol and acetaminophen exposure

Risk of colorectal cancer in self-reported inflammatory bowel disease and modification of risk by statin and NSAID use

BACKGROUND: Statins and nonsteroidal anti-inflammatory drugs (NSAIDs) are associated with reduced risk of colorectal cancer (CRC) in some studies. The objective of this study was to quantify the relative risk of inflammatory bowel disease (IBD) as a risk factor for CRC and to estimate whether this risk may be modified by long-term use of NSAIDs or statins. METHODS: The Molecular Epidemiology of Colorectal Cancer study is a population-based, case-control study of incident colorectal cancer in northern Israel and controls matched by age, sex, clinic, and ethnicity. Personal histories of IBD and medication use were measured by structured, in-person interview. The relative risk of IBD and effect modification by statins and NSAIDs were quantified by conditional and unconditional logistic regression. RESULTS: Among 1921 matched pairs of CRC cases and controls, a self-reported history of IBD was associated with a 1.9-fold increased risk of CRC (95% confidence interval [CI], 1.12-3.26). Long-term statin use was associated with a reduced risk of both IBD-associated CRC (odds ratio [OR] = 0.07; 95% CI, 0.01-0.78) and non-IBD CRC (OR = 0.49; 95% CI, 0.39-0.62). Stratified analysis suggested that statins may be more protective among those with IBD (ratio of OR = 0.14; 95% CI, 0.01-1.31; P = .51), although not statistically significant. NSAID use in patients with a history of IBD was suggestive of reduced risk of CRC but did not reach statistical significance (OR = 0.47; 95% CI, 0.12-1.86). CONCLUSIONS: The risk of CRC was elevated 1.9-fold in patients with IBD. Long-term statin use was associated with reduced risk of CRC in patients with IBD. Cancer 2011. © 2010 American Cancer Society.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/84387/1/25731_ftp.pd

Metabolic Syndrome Is Associated with Greater Histologic Severity, Higher Carbohydrate, and Lower Fat Diet in Patients with NAFLD

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73077/1/j.1572-0241.2006.00719.x.pd

Rationale and design of the POLEM trial: avelumab plus fluoropyrimidine-based chemotherapy as adjuvant treatment for stage III mismatch repair deficient or POLE exonuclease domain mutant colon cancer: a phase III randomised study

BACKGROUND:10%-15% of early-stage colon cancers harbour either deficient mismatch repair (dMMR), microsatellite instability high (MSI-H) or POLE exonuclease domain mutations, and are characterised by high tumour mutational burden and increased lymphocytic infiltrate. Metastatic dMMR colon cancers are highly sensitive to immune checkpoint inhibition, and recent data show POLE-mutant tumours are similarly responsive. We are conducting a phase III randomised trial to determine if the addition of the anti-PD-L1 antibody avelumab following adjuvant chemotherapy improves disease-free survival (DFS) in patients with stage III dMMR/MSI-H or POLE mutant colon cancer and is a cost-effective approach for the UK National Health Service (NHS). METHODS:We are recruiting patients with completely resected, stage III colon cancer confirmed to have dMMR/MSI-H, locally or POLE exonuclease domain mutation on central testing. Eligible patients are randomised in a 1:1 ratio to standard fluoropyrimidine-based chemotherapy (capecitabine, oxaliplatin for 12 weeks or capecitabine for 24 weeks) or chemotherapy, followed by avelumab (10 mg/kg, 2 weekly for 24 weeks). Stratification is by chemotherapy received and MMR/MSI-H status. The primary endpoint is DFS. Secondary endpoints include overall survival, toxicity, quality of life and health resource use. The 3-year DFS rate in the control arm is expected to be ~75%. Avelumab is expected to improve the 3-year DFS rate by 12% (ie, 87%). Target accrual is 402 patients, which provides 80% power to detect an HR of 0.48 for DFS at a two-sided alpha of 0.05. This national, multicentre phase III trial is sponsored by the Royal Marsden NHS Foundation Trust and it is anticipated that approximately 40 centres in the UK will participate. This study opened to recruitment in August 2018. TRIAL REGISTRATION NUMBER:NCT03827044

Human papillomavirus is not associated with colorectal cancer in a large international study

Recent publications have reported an association between colon cancer and human papillomaviruses (HPV), suggesting that HPV infection of the colonic mucosa may contribute to the development of colorectal cancer. The GP5+/GP6+ PCR reverse line blot method was used for detection of 37 types of human papillomavirus (HPV) in DNA from paraffin-embedded or frozen tissues from patients with colorectal cancer (n = 279) and normal adjacent tissue (n = 30) in three different study populations, including samples from the United States (n = 73), Israel (n = 106) and Spain (n = 100). Additionally, SPF10 PCR was run on all samples (n = 279) and the Innogenetics INNO-LiPA assay was performed on a subset of samples (n = 15). All samples were negative for all types of HPV using both the GP5+/GP6+ PCR reverse line blot method and the SPF10 INNO-LiPA method. We conclude that HPV types associated with malignant transformation do not meaningfully contribute to adenocarcinoma of the colon

Identification of a Specific Vimentin Isoform That Induces an Antibody Response in Pancreatic Cancer

Pancreatic cancer has a poor prognosis, in part due to lack of early detection. The identification of circulating tumor antigens or their related autoantibodies provides a means for early cancer diagnosis. We have used a proteomic approach to identify proteins that commonly induce a humoral response in pancreatic cancer. Proteins from a pancreatic adenocarcinoma cell line (Panc-1) were subjected to two-dimensional PAGE, followed by Western blot analysis in which individual sera were tested for autoantibodies. Sera from 36 newly diagnosed patients with pancreatic cancer, 18 patients with chronic pancreatitis and 15 healthy subjects were analyzed. Autoantibodies were detected against a protein identified by mass spectrometry as vimentin, in sera from 16/36 patients with pancreatic cancer (44.4%). Only one of 18 chronic pancreatitis patients and none of the healthy controls exhibited reactivity against this vimentin isoform. Interestingly, none of several other isoforms of vimentin detectable in 2-D gels exhibited reactivity with patient sera. Vimentin protein expression levels were investigated by comparing the integrated intensity of spots visualized in 2-D PAGE gels of various cancers. Pancreatic tumor tissues showed greater than a 3-fold higher expression of total vimentin protein than did the lung, colon, and ovarian tumors that were analyzed. The specific antigenic isoform was found at 5–10 fold higher levels. The detection of autoantibodies to this specific isoform of vimentin may have utility for the early diagnosis of pancreatic cancer