Do food and stress biomarkers work for wastewater-based epidemiology? A critical evaluation.

Dietary characteristics and oxidative stress are closely linked to the wellbeing of individuals. In recent years, various urinary biomarkers of food and oxidative stress have been proposed for use in wastewater-based epidemiology (WBE), in efforts to objectively monitor the food consumed and the oxidative stress experienced by individuals in a wastewater catchment. However, it is not clear whether such biomarkers are suitable for wastewater-based epidemiology. This study presents a suite of 30 urinary food and oxidative stress biomarkers and evaluates their applicability for WBE studies. This includes 22 biomarkers which were not previously considered for WBE studies. Daily per capita loads of biomarkers were measured from 57 wastewater influent samples from nine Australian catchments. Stability of biomarkers were assessed using laboratory scale sewer reactors. Biomarkers of consumption of vitamin B2, vitamin B3 and fibre, as well as a component of citrus had per capita loads in line with reported literature values despite susceptibility of degradation in sewer reactors. Consumption biomarkers of red meat, fish, fruit, other vitamins and biomarkers of stress had per capita values inconsistent with literature findings, and/or degraded rapidly in sewer reactors, indicating that they are unsuitable for use as WBE biomarkers in the traditional quantitative sense. This study serves to communicate the suitability of food and oxidative stress biomarkers for future WBE research.

Carotid Webs and Recurrent Ischemic Strokes in the Era of CT Angiography.

BACKGROUND AND PURPOSE: Carotid webs may cause recurrent ischemic stroke. We describe the prevalence, demographics, clinical presentation, imaging features, histopathology, and stroke risk associated with this under-recognized lesion. MATERIALS AND METHODS: A carotid web was defined on CTA as a thin intraluminal filling defect along the posterior wall of the carotid bulb just beyond the carotid bifurcation on oblique sagittal section CTA that was seen as a septum on axial CTA. Using a prospective case series from April 2013 to April 2014, we describe the demographics, spectrum of imaging features on CTA, and histopathology of these carotid webs. From a retrospective analysis of patients at our center from May 2012 to April 2013 who had a baseline head and neck CTA followed by a brain MR imaging within 1-2 days of the CTA, we determine the period prevalence of carotid webs and the prevalence of ipsilateral stroke on imaging. RESULTS: In the prospective series, the mean age was 50 years (range, 41-55 years); 5/7 patients were women. Recurrent stroke was seen in 5/7 (71.4%) patients with the carotid web; time to recurrence ranged from 1 to 97 months. Histopathology suggested a high probability of fibromuscular dysplasia. In the retrospective series, carotid webs were seen in 7/576 patients for a hospital-based-period prevalence of 1.2% (95% CI, 0.4%-2.5%). Two of these 7 patients had acute stroke in the vascular territory of the carotid web. CONCLUSIONS: A carotid web may contribute to recurrent ischemic stroke in patients with no other determined stroke mechanism. Intimal variant fibromuscular dysplasia is the pathologic diagnosis in most cases. The prevalence of carotid web is low, while the optimal management strategy remains unknown.

Small bowel resection induces long-term changes in the enteric microbiota of mice.

PURPOSE: The enteric microbiome is known to play a major role in healthy gut homeostasis and several disease states. It may also contribute to both the intestinal recovery and complications that occur in patients with short bowel syndrome. The extent and nature of alterations to the gut microbiota following intestinal resection, however, are not well studied in a controlled setting. The purpose of this investigation is to characterize the effects of massive small bowel resection on the murine enteric microflora. METHODS: Wild-type C57BL6 mice, following a week of acclamation to a liquid rodent diet, underwent either 50% proximal small bowel resection (SBR) or a sham operation. Mice were sacrificed, and enteric contents from the small bowel, cecum, and stool were harvested at 7 and 90 days post-operatively. DNA was isolated, and the V3-V5 regions of the 16s rRNA gene amplified and pyrosequenced on a Roche 454 platform. Sequences were clustered into operation taxonomic units and classified. Communities were then analyzed for diversity and phylogenic composition. RESULTS: In the long-term group, the microbes inhabiting the ileum of mice undergoing SBR and sham operation differed significantly at the genus level (p < 0.001). Small bowel contents collected before and after SBR also differed significantly (p = 0.006). This was driven by an increase in Lactobacillus and decrease in Enterobacteriaceae species in mice undergoing SBR. No difference was seen in the long-term stool or in stool, cecal, or ileal contents in the short-term. No difference in microbial community diversity was found in any group. CONCLUSION: Bowel resection induces long-term changes in the microbial community of the murine ileum, but not at more distal sites of the gastrointestinal tract. The increase in Lactobacillus encountered small bowel of resected mice correlates with limited previous studies. These changes may reflect an adaptive response of the microbiota to maximize energy extraction, but further studies are needed to establish the role played by this altered community.

Differentiating between Hemorrhagic Infarct and Parenchymal Intracerebral Hemorrhage.

Differentiating hemorrhagic infarct from parenchymal intracerebral hemorrhage can be difficult. The immediate and long-term management of the two conditions are different and hence the importance of accurate diagnosis. Using a series of intracerebral hemorrhage cases presented to our stroke unit, we aim to highlight the clues that may be helpful in distinguishing the two entities. The main clue to the presence of hemorrhagic infarct on computed tomography scan is the topographic distribution of the stroke. Additional imaging modalities such as computed tomography angiogram, perfusion, and magnetic resonance imaging may provide additional information in differentiating hemorrhagic infarct from primary hemorrhages.

Role of antineutrophil cytoplasmic antibodies in an ethnically distinct population: Korean patients with ulcerative colitis.

OBJECTIVES: Studies have suggested that antineutrophil cytoplasmic antibodies (ANCA), known as a useful diagnostic marker in patients with ulcerative colitis (UC), may have a genetic basis, particularly in association with HLA class II genes. Because most studies examining the role of ANCA in UC have been performed in ethnically undefined populations, we have analyzed ANCA status in an ethnically distinct group of patients with UC. METHODS: Serum samples from 24 Korean patients with a known diagnosis of UC and 58 healthy Koreans were examined for the presence of ANCA, using a fixed neutrophil enzyme-linked immunosorbent assay. ANCA-binding patterns were examined by indirect immunofluorescence. RESULTS: The incidence of ANCA in 83.3% of Korean patients with UC was significantly higher than in controls (p < 0.0001). The mean binding level at a 1:100 dilution and the titer of ANCA were significantly higher in patients with UC than in controls. Among UC patients with ANCA, there was also a high incidence of perinuclear binding pattern. In contrast, there was no relationship between ANCA and age of patients, duration, activity, or extent of disease. CONCLUSIONS: High sensitivity and specificity of ANCA in an ethnically distinct group of patients with UC show that ANCA expression may not be ethnically determined, and they confirm the utility of ANCA as a useful diagnostic indicator of UC in an ethnically diverse groups of patients.

Colon cancer surveillance.

Colorectal cancer is one of the most important risk factors affecting the long-term outcome of patients with ulcerative colitis. Therefore, an extensive effort has been devoted to prevent and reduce the mortality related to colorectal cancer through cancer surveillance programs. Studies have demonstrated that cancer surveillance can lead to an improved outcome in patients who go on to develop cancer. Given increasing reports of cancer risk in Crohn's disease, further studies examining the potential impact of a similar program in Crohn's disease should be considered.

Safety of surveillance colonoscopy in long-standing ulcerative colitis.

OBJECTIVE: Because of the increased risk of colorectal cancer in patients with long-standing ulcerative colitis, colonoscopic surveillance for the detection of dysplasia is currently recommended as a method of identifying high-risk patients. However, the hazard of colonoscopy with multiple biopsies in such patients is not well known. Our objective was to assess the safety of surveillance colonoscopy in patients with long-standing ulcerative colitis. METHODS: To accomplish our objective, we conducted a retrospective analysis of results and follow-up of surveillance colonoscopies. RESULTS: A total of 6,727 biopsies were obtained during 384 colonoscopies, with a median of 17 biopsies per colonoscopy. Nineteen studies were performed in a setting of underlying stricture. A single complication of a silent perforation occurred in a patient with an underlying stricture. No instances of bleeding, infection, respiratory distress, myocardial infarction, or death resulted from the procedure. CONCLUSION: Our findings suggest that surveillance colonoscopy with multiple biopsies is a relatively safe procedure. Given increasing evidence of the survival benefit derived from the procedure, we believe these results render further support for the current practice of surveillance colonoscopy in patients with ulcerative colitis.

Immunomodulator therapy in inflammatory bowel disease.

The introduction of immunomodulator therapy in the treatment of patients with inflammatory bowel disease (IBD) has provided an important tool in modifying the mucosal immune system thought to be important in the pathogenesis of IBD. Currently available immunomodulating agents include azathioprine, 6-mercaptopurine, cyclosporin, and methotrexate. Recent clinical trials have demonstrated that these agents have an important therapeutic role in the treatment of patients who are either refractory or intolerant to traditional medical therapy. They are useful in the induction and maintenance of remission for both ulcerative colitis and Crohn's disease. However, these agents have significant toxicities and limited efficacy. In addition, potential risks of malignancy and infection limit their indiscriminate use. Thus, with the better understanding of the molecular basis of mucosal immunity, innovative immune-modifying therapies, such as antagonists of cytokines and inhibitors of T-cell activation, are being developed. It is likely that these exciting developments will soon result in specific immune modulating therapy with improved efficacy and reduced toxicity in the treatment of patients with IBD.

Similarity of colorectal cancer in Crohn's disease and ulcerative colitis: implications for carcinogenesis and prevention.

Colorectal cancer is the most frequent malignant complication in patients with inflammatory bowel disease. Eighty patients with colorectal cancer complicating Crohn's disease (CD) or ulcerative colitis (UC) with median ages at diagnosis of colorectal cancer of 54.5 years and 43.0 years respectively were studied. The median duration of disease to the diagnosis of cancer was long (CD 15 years; UC 18 years). Most cancers developed after more than eight years of disease (CD 75%; UC 90%). Patients with multiple carcinomas at diagnosis were equally common (CD 11%; UC 12%). Carcinoma occurred in the area of macroscopic disease in most patients (CD 85%; UC 100%). Mucinous and signet ring histological features were equally common (CD 29%; UC 21%). Dysplasia was present with similar frequency in both diseases (CD 73%; UC 79%). The overall five year survival rates were also similar (CD 46%; UC 50%). These findings show that carcinomas complicating CD and UC have strikingly similar clinicopathological features and suggest that a common underlying process, such as chronic inflammation, maybe important in the pathogenesis of colorectal carcinoma.

Cholangiocarcinoma and Crohn's disease.

Cholangiocarcinoma is an infrequent complication of inflammatory bowel disease. Although increasing numbers of cholangiocarcinomas are being reported in association with ulcerative colitis, the occurrence of this disease in patients with Crohn's disease is rare. To understand this complication better, we have reported the case of a patient with Crohn's disease in whom cholangiocarcinoma subsequently developed and reviewed the literature.

Colonoscopic surveillance reduces mortality from colorectal cancer in ulcerative colitis.

BACKGROUND: To control the increased risk of colorectal carcinoma in patients with long-standing ulcerative colitis, surveillance colonoscopy is widely recommended. METHODS: To assess the role of colonoscopic surveillance in affecting colorectal carcinoma-related mortality, an outcome analysis was performed. RESULTS: Among the total of 41 patients who developed carcinoma associated with ulcerative colitis, 19 patients were under colonoscopic surveillance and 22 patients were not. Carcinoma was detected at a significantly earlier Dukes' stage in the surveillance group (P = 0.039). Four patients in the surveillance group died, compared with 11 patients in the no-surveillance group. The 5-year survival rate was 77.2% for the surveillance group and 36.3% for the no-surveillance group (P = 0.026). CONCLUSIONS: These results suggest that colonoscopic surveillance reduces colorectal carcinoma-related mortality by allowing the detection of carcinoma at an earlier Dukes' stage.

The modulation of growth by HMBA in PKC overproducing HT29 colon cancer cells.

To examine whether protein kinase C (PKC) plays a role in mediating growth inhibitory effects of hexamethylene bisacetamide (HMBA) we compared a control H29 colon cancer cell line to a derivative, HT29-PKC7, that overexpresses high levels of PKC beta 1. We found that although HMBA markedly inhibited the growth of the control cells, no inhibition was seen with the HT29-PKC7 cells. On the other hand the tumor promoter 12-0-tetradecanoyl-phorbol-13 acetate inhibited the growth of HT29-PKC7 cells, but no inhibition was seen with the control cells. Maximum inhibition of the growth of both cell lines was obtained by combined treatment with HMBA and TPA. These results may be relevant to the use of HMBA in combination with other agents in the therapy of specific cancers.

Overexpression of protein kinase C in HT29 colon cancer cells causes growth inhibition and tumor suppression.

By using a retrovirus-derived vector system, we generated derivatives of the human colon cancer cell line HT29 that stably overexpress a full-length cDNA encoding the beta 1 isoform of rat protein kinase C (PKC). Two of these cell lines, PKC6 and PKC7, displayed an 11- to 15-fold increase in PKC activity when compared with the C1 control cell line that carries the vector lacking the PKC cDNA insert. Both of the overexpresser cell lines exhibited striking alterations in morphology when exposed to the tumor promoter 12-O-tetradecanoyl-phorbol-13-acetate (TPA). Following exposure to TPA, PKC6 and PKC7 cells displayed increased doubling time, decreased saturation density, and loss of anchorage-independent growth in soft agar; but these effects were not seen with the C1 cells. Also, in contrast to the control cells, the PKC-overproducing cells failed to display evidence of differentiation, as measured by alkaline phosphatase activity, when exposed to sodium butyrate. In addition, the PKC-overexpresser cells displayed decreased tumorigenicity in nude mice, even in the absence of treatment with TPA. These results provide the first direct evidence that PKC can inhibit tumor cell growth. Thus, in some tumors, PKC might act as a growth-suppressor gene.