Atypical presentation of Clostridioides difficile pseudomembranous colitis with laboratory rejection of stool specimen.

Clostridioides (formerly Clostridium) difficile is a major cause of nocosomial infection in the USA and worldwide. It has a wide spectrum of presentation, ranging from an asymptomatic carrier state to fulminant colitis. Pseudomembranous colitis is a manifestation of severe C. difficile infection (CDI), typically with progressive symptoms including watery diarrhoea, abdominal cramping and fevers and elevated white cell count and/or creatinine. It is diagnosed on three levels, including clinical assessment, stool assays and visualisation of the colonic mucosa. Laboratories will reject stools that do not meet criteria for testing. In the era of molecular testing for the presence of toxigenic C. difficile DNA, which only indicates the potential for infection, it is vital to use clinical evaluation in the diagnosis of CDI. We present an atypical case of pseudomembranous colitis affecting the right colon in a patient whose stools were rejected multiple times for C. difficile testing.

Bowel Obstruction and Hydronephrosis Due to an Over-the-Scope Clip.

An over-the-scope clip is a type of endoscopically placed clip used to treat gastrointestinal perforation, bleeding, or fistula. After the defect heals, the clip usually passes uneventfully through the gastrointestinal tract. An uncommon complication of over-the-scope clip placement is intestinal obstruction caused by luminal stenosis at the site of clip placement. Intestinal obstruction can rarely cause other downstream complications such as hydronephrosis from extrinsic compression of the urinary tract. We report a rare case of bilateral hydronephrosis caused by bowel obstruction from a migrated endoscopically placed clip.

Long-term neurocognitive outcome and auditory event-related potentials after complex febrile seizures in children.

OBJECTIVES: Whether prolonged or complex febrile seizures (FS) produce long-term injury to the hippocampus is a critical question concerning the neurocognitive outcome of these seizures. Long-term event-related evoked potential (ERP) recording from the scalp is a noninvasive technique reflecting the sensory and cognitive processes associated with attention tasks. This study aimed to investigate the long-term outcome of neurocognitive and attention functions and evaluated auditory event-related potentials in children who have experienced complex FS in comparison with other types of FS. METHODS: One hundred and forty-seven children aged more than 6 years who had experienced complex FS, simple single FS, simple recurrent FS, or afebrile seizures (AFS) after FS and age-matched healthy controls were enrolled. Patients were evaluated with Wechsler Intelligence Scale for Children (WISC; Chinese WISC-IV) scores, behavior test scores (Chinese version of Conners' continuous performance test, CPT II V.5), and behavior rating scales. Auditory ERPs were recorded in each patient. RESULTS: Patients who had experienced complex FS exhibited significantly lower full-scale intelligence quotient (FSIQ), perceptual reasoning index, and working memory index scores than did the control group but did not show significant differences in CPT scores, behavior rating scales, or ERP latencies and amplitude compared with the other groups with FS. We found a significant decrease in the FSIQ and four indices of the WISC-IV, higher behavior rating scales, a trend of increased CPT II scores, and significantly delayed P300 latency and reduced P300 amplitude in the patients with AFS after FS. CONCLUSION: We conclude that there is an effect on cognitive function in children who have experienced complex FS and patients who developed AFS after FS. The results indicated that the WISC-IV is more sensitive in detecting cognitive abnormality than ERP. Cognition impairment, including perceptual reasoning and working memory defects, was identified in patients with prolonged, multiple, or focal FS. These results may have implications for the pathogenesis of complex FS. Further comprehensive psychological evaluation and educational programs are suggested.

A novel high throughput approach to screen for cardiac arrhythmic events following stem cell treatment.

Although stem cell therapy is promising for repairing damaged cardiac tissue and improving heart function, there are safety concerns, especially regarding the risk of arrhythmias, which can be life threatening. To address this issue, we propose to develop a novel screening system to evaluate arrhythmic risk associated with stem cell therapy using a high-throughput multielectrode array system that can measure conduction velocity and action potential duration in cardiomyocytes co-cultured with different types of stem cells, such as mesenchymal stem cells, skeletal myoblasts, and resident cardiac stem cells. We will assess the arrhythmic potential of each of these types of stem cells under normoxic and hypoxic conditions, with/without application of oxidative stress or catecholamines. We hypothesize that these methods will prove to be an effective way to screen for arrhythmic risk of cardiac stem cell therapy. Ultimately, our approach can potentially be personalized to develop a robust screening protocol in order to identify which stem cell type carries the least amount of risk for arrhythmia. This system will have great clinical benefit to improve the risk/benefit ratio of human stem cell therapy for heart disease.

NASCA report 2: Longitudinal study of relationship of exposure to space radiation and risk of lens opacity.

The NASA Study of Cataract in Astronauts (NASCA) was designed to measure the impact of exposure to space radiation on progression rates of cortical, nuclear, and posterior subcapsular cataract in U.S. astronauts who have flown in space and comparison groups of astronauts who had not flown in space, and subjects with a history of military aviation. We present our analyses of 5 years of data with an average of 3.8 exams per subject. All subjects had digital lens images with the Nidek EAS 1000 Lens Imaging System. Because of high variability and skewness of opacity measures, nonparametric methods were used to test for association between rates of opacification and space radiation exposure. First, median regression was used to collapse longitudinal data into robust estimates of progression rates (opacity severity compare to time for each eye of each subject). To quantify and test for a radiation effect, median regression with the dependent variable being the maximum of the two slopes (OD and OS) per subject was then used, adjusting for the confounding variables of age, nutritional, and sun-exposure histories. Median regression showed evidence of an association between the rate of cortical progression in the worse eye with radiation dose and age. The estimated median progression rate from space radiation being 0.25 ± 0.13% lens area/Sv/year (P = 0.062). We found no relationship between radiation exposure and progression of aggregate area of posterior subcapsular cataract or nuclear progression rates. However, longer follow-up may be needed to further understand any impact of space radiation on progression rates for posterior subcapsular cataracts and nuclear cataracts, and to characterize changes to visual acuity.

Age-changed normative auditory event-related potential value in children in Taiwan.

BACKGROUND/PURPOSE: Event-related potentials (ERPs) reflect higher cortical function and the P3 (P300) wave has been associated with various sensory, cognitive, and attention processes. The aims of this study were to understand the age-related change in ERPs in children between the ages of 6 and 13 years and to establish a normal reference value for Taiwanese children for use in future study of neurocognitive dysfunction in children. METHODS: Using an auditory oddball paradigm, ERPs were recorded in 63 mentally and physically normal children ages 6 to 13 years. Parietal, central, and frontal ERP long-latency components (N1, P2, N2, P3) were measured in each test participant. RESULTS: Linear regression analysis demonstrated a significant linear decrease in P3, P2, N2, and N1 latencies and a significant linear increase in P3, P2, and N1 amplitudes in children between the ages of 6 and 13 years. P3 latency was significantly longer in children ages 6-7 years than in older children. The parietal P3 latency decreases 6.7 msec per year from ages 6 to 13 years. A wide variation in P3 latency in the children ages 6-7 years and a significant increase in P3 amplitude in those ages 12-13 years were observed from our data. A significant increase in P2 amplitude was also observed in children older than 10 years. CONCLUSION: The authors conclude that there exists an age-related change in ERP latency and amplitude during childhood. A negative correlation between ERP latencies and age and a positive correlation between ERP amplitude and age were found in this study. The authors emphasize that the auditory ERP value in children is not equal to that of adults. A normative auditory ERP value in children should be established prior to clinical application.

NASA study of cataract in astronauts (NASCA). Report 1: Cross-sectional study of the relationship of exposure to space radiation and risk of lens opacity.

The NASA Study of Cataract in Astronauts (NASCA) is a 5-year longitudinal study of the effect of space radiation exposure on the severity/progression of nuclear, cortical and posterior subcapsular (PSC) lens opacities. Here we report on baseline data that will be used over the course of the longitudinal study. Participants include 171 consenting astronauts who flew at least one mission in space and a comparison group made up of three components: (a) 53 astronauts who had not flown in space, (b) 95 military aircrew personnel, and (c) 99 non-aircrew ground-based comparison subjects. Continuous measures of nuclear, cortical and PSC lens opacities were derived from Nidek EAS 1000 digitized images. Age, demographics, general health, nutritional intake and solar ocular exposure were measured at baseline. Astronauts who flew at least one mission were matched to comparison subjects using propensity scores based on demographic characteristics and medical history stratified by gender and smoking (ever/never). The cross-sectional data for matched subjects were analyzed by fitting customized non-normal regression models to examine the effect of space radiation on each measure of opacity. The variability and median of cortical cataracts were significantly higher for exposed astronauts than for nonexposed astronauts and comparison subjects with similar ages (P=0.015). Galactic cosmic space radiation (GCR) may be linked to increased PSC area (P=0.056) and the number of PSC centers (P=0.095). Within the astronaut group, PSC size was greater in subjects with higher space radiation doses (P=0.016). No association was found between space radiation and nuclear cataracts. Cross-sectional data analysis revealed a small deleterious effect of space radiation for cortical cataracts and possibly for PSC cataracts. These results suggest increased cataract risks at smaller radiation doses than have been reported previously.

Temporal changes in mouse aortic wall gene expression during the development of elastase-induced abdominal aortic aneurysms.

OBJECTIVE: To characterize temporal changes in mouse aortic wall gene expression associated with the development of experimental abdominal aortic aneurysms. METHODS: C57BL/6 mice underwent transient perfusion of the abdominal aorta with either elastase (n = 61) or heat-inactivated elastase as a control (n = 68). Triplicate samples of radiolabeled aortic wall complementary DNA were prepared at intervals of 0, 3, 7, 10, and 14 days, followed by hybridization to nylon microarrays (1181 genes). Autoradiographic intensity data were normalized by conversion to z scores, and differences in gene expression were defined by two-tailed z tests at a significance threshold of P < .01. RESULTS: Elastase perfusion caused a progressive increase in aortic diameter up to 14 days accompanied by transmural inflammation and destructive remodeling of the elastic media. No aneurysms occurred in the control group. Compared with healthy aorta, 336 genes exhibited significant alterations during at least 1 interval after elastase perfusion (135 at more than 1 interval and 14 at all intervals), with pronounced increases for interleukin 6, cyclin E2, interleukin 1beta, osteopontin, CD14/lipopolysaccharide receptor, P-selectin glycoprotein ligand 1, and gelatinase B/matrix metalloproteinase 9 (all >20-fold on day 3). Sixty-two genes exhibited synchronous alterations in the elastase and control groups, thus suggesting a nonspecific response. By direct comparisons between the elastase and control groups, there were 384 genes with significant differences in expression for at least 1 interval after aortic perfusion, including 234 with differential upregulation (eg, p44MAPK/ERK1, osteopontin, heat shock protein 84, hypoxia-inducible factor 1alpha, apolipoprotein E, monocyte chemotactic protein 3, MIG (monokine induced by gamma interferon), and interleukin 2 receptor gamma) and 163 with differential downregulation (eg, prothrombin, granzyme B, ataxia telangiectasia mutated, and interleukin-converting enzyme). CONCLUSIONS: Development of elastase-induced abdominal aortic aneurysms in mice is accompanied by altered aortic wall expression of genes associated with acute and chronic inflammation, matrix degradation, and vascular tissue remodeling. Knowledge of these alterations will facilitate further studies on the functional molecular mechanisms that underlie aneurysmal degeneration.

Carbohydrate intake and glycemic index in relation to the odds of early cortical and nuclear lens opacities.

BACKGROUND: Animal studies suggest a role for dietary carbohydrate in cataractogenesis. However, few published human studies have evaluated associations between carbohydrate nutrition and lens opacification. OBJECTIVE: Our objective was to test the hypothesis that long-term carbohydrate intake and dietary glycemic index are associated with the odds of early cortical and nuclear opacities. DESIGN: Subjects were 417 Boston-area members of the Nurses' Health Study cohort aged 53-73 y. Dietary information was based on an average from 5 semiquantitative food-frequency questionnaires collected over a 14-y period. Opacities were assessed by using the Lens Opacity Classification System III (LOCS III). We used eyes (n = 711) as the unit of analysis and generated odds ratios by using a generalized estimating approach to logistic regression to account for the lack of independence between the 2 eyes of each subject. RESULTS: After multivariate adjustment, the odds of cortical opacities (LOCS III >/=1.0) among women in the highest tertile of carbohydrate intake (>/=200 g/d) was 2.46 times (95% CI: 1.30, 4.64; P for trend = 0.005) that among women in the lowest tertile (<185 g/d). This association was not affected by adjustment for dietary glycemic index, which was not associated with early cortical opacities. Carbohydrate nutrition was not associated with the odds of nuclear opacities (LOCS III >/=2.5). CONCLUSIONS: These data suggest that carbohydrate quantity, but not carbohydrate quality, is associated with early cortical opacities, and that neither the quantity nor the quality of dietary carbohydrate affects the risk of nuclear opacities in middle-aged women.

Long-term nutrient intake and 5-year change in nuclear lens opacities.

OBJECTIVE: To determine if usual nutrient intake is related to a 5-year change in the amount of lens nuclear opacification assessed by computer-assisted image analysis. DESIGN: A sample of 408 Boston, Mass-area women from the Nurses' Health Study aged 52 to 74 years at baseline participated in a 5-year study related to nutrition and vision. Usual nutrient intake was calculated as the average intake from 5 food frequency questionnaires that were collected over a 13- to 15-year period before the baseline evaluation of lens nuclear density. Duration of vitamin supplement use before baseline was determined from 7 questionnaires collected during this same period. We assessed the degree of nuclear density (opacification) using computer-assisted image analysis of digital lens images with amount of nuclear density measured as a function of average pixel gray scale, ranging from 0 (clear) to 255 (black). RESULTS: Median (range) baseline and follow-up nuclear densities were 44 (19 to 102) and 63 (32 to 213). The median (range) 5-year change in nuclear density was 18 (-29 to 134) and was positively correlated with the amount of opacification at baseline (Spearman correlation coefficient = 0.35; P<.001). Geometric mean 5-year change in nuclear density was inversely associated with the intake of riboflavin (P trend = .03) and thiamin (P trend = .04) and duration of vitamin E supplement use (P trend = .006). CONCLUSION: Our results suggest that long-term use of vitamin E supplements and higher riboflavin and/or thiamin intake may reduce the progression of age-related lens opacification.

Weight status, abdominal adiposity, diabetes, and early age-related lens opacities.

BACKGROUND: The association between weight status and the risk of lens opacities has received little attention. OBJECTIVE: We examined the cross-sectional relations of body mass index (BMI; in kg/m(2)), waist circumference, and diabetes with the presence of age-related lens opacities. DESIGN: Eye examinations were conducted in 466 Boston-area women aged 53-73 y who were without previously diagnosed cataracts and were part of the Nurses' Health Study cohort. Weight, height, waist, and hip measurements were obtained by self-report. Lens status was evaluated by using the Lens Opacification Classification System III (LOCS III). BMI and waist circumference were used as measures of overweight and abdominal adiposity, respectively. Nuclear, cortical, and posterior subcapsular (PSC) opacities were defined as LOCS III scores > or = 2.5, > or = 1.0, and > or = 0.5, respectively. Diabetes was defined as a history of type 2 diabetes or as a fasting plasma glucose concentration > or = 7.0 mmol/L. RESULTS: Women with diabetes were significantly more likely to have PSC opacities [odds ratio (OR): 4.1; 95% CI: 1.8, 9.4] than were women with fasting plasma glucose concentrations < 6.1 mmol/L. Women with a BMI > or = 30 had a higher prevalence of PSC opacities than did women with a BMI < 25 (OR: 2.5; 1.2, 5.2), and women with a waist circumference > or = 89 cm had a higher prevalence of PSC opacities than did those with a waist circumference < 80 cm (OR: 2.3; 1.0, 5.2). Diabetes and measures of adiposity were unrelated to the prevalence of cortical and nuclear opacities. CONCLUSIONS: Diabetes is a strong risk factor for PSC opacities, and overweight and abdominal adiposity may be risk factors for PSC opacities.

Altered patterns of gene expression distinguishing ascending aortic aneurysms from abdominal aortic aneurysms: complementary DNA expression profiling in the molecular characterization of aortic disease.

OBJECTIVES: The purpose of this study was to profile altered patterns of gene expression that characterize degenerative ascending thoracic aortic aneurysms and to compare these patterns with those observed for infrarenal abdominal aortic aneurysms. METHODS: Full-thickness aortic wall tissues were obtained during surgical repair of degenerative thoracic aortic aneurysms and infrarenal abdominal aortic aneurysms (n = 4 each), with normal thoracic and abdominal aortas from organ transplant donors used as control preparations. Radiolabeled complementary DNA was prepared for each specimen and hybridized to complementary DNA microarrays, and differential levels of gene expression between aneurysmal and normal aortic tissues at each site were assessed by parametric statistics. RESULTS: Of 1185 genes examined, 112 (9.5%) were differentially expressed (P <.05) between thoracic aortic aneurysms and normal thoracic aorta, with 105 increased and 7 decreased. There were 104 genes (8.8%) differentially expressed between infrarenal abdominal aortic aneurysms and normal abdominal aorta (65 increased and 39 decreased). Quantitative increases in expression for 97 genes were unique to thoracic aortic aneurysms, whereas increases for 61 genes were unique to infrarenal abdominal aortic aneurysms. Although 8 gene products were significantly altered in both thoracic and infrarenal abdominal aortic aneurysms, these changes were directionally concordant for only 4 (matrix metalloproteinase 9/gelatinase B, v-yes-1 oncogene, mitogen-activated protein kinase 9, and intercellular adhesion molecule 1/CD54). Results for 9 genes were independently confirmed by quantitative reverse transcriptase-polymerase chain reaction. CONCLUSIONS: Thoracic aortic aneurysms and infrarenal abdominal aortic aneurysms exhibit distinct patterns of gene expression relative to normal aorta from the same sites, with most alterations being unique to each disease. Degenerative aneurysms arising in different locations are thus characterized by a high degree of molecular heterogeneity, reflecting different pathophysiologic mechanisms.

Long-term intake of vitamins and carotenoids and odds of early age-related cortical and posterior subcapsular lens opacities.

BACKGROUND: Proper nutrition appears to protect against cataracts. Few studies have related nutrition to the odds of developing cortical or posterior subcapsular (PSC) cataracts. OBJECTIVE: We assessed the relation between usual nutrient intakes and age-related cortical and PSC lens opacities. DESIGN: We studied 492 nondiabetic women aged 53-73 y from the Nurses' Health Study cohort who were without previously diagnosed cataracts. Usual nutrient intake was calculated as the average intake from 5 food-frequency questionnaires collected over a 13-15-y period before the eye examination. Duration of vitamin supplement use was determined from 7 questionnaires collected during this same period. We defined cortical opacities as grade > or = 0.5 and subcapsular opacities as grade > or =0.3 of the Lens Opacities Classification System III. RESULTS: Some lenses had more than one opacity. No nutrient measure was related to prevalence of opacities in the full sample, but significant interactions were seen between age and vitamin C intake (P = 0.02) for odds of cortical opacities and between smoking status and folate (P = 0.02), alpha-carotene (P = 0.02), beta-carotene (P = 0.005), and total carotenoids (P = 0.02) for odds of PSC opacities. For women aged <60 y, a vitamin C intake > or = 362 mg/d was associated with a 57% lower odds ratio (0.43; 95% CI: 0.2, 0.93) of developing a cortical cataract than was an intake <140 mg/d, and use of vitamin C supplements for > or = 10 y was associated with a 60% lower odds ratio (0.40; 0.18, 0.87) than was no vitamin C supplement use. Prevalence of PSC opacities was related to total carotenoid intake in women who never smoked (P = 0.02). CONCLUSIONS: Our results support a role for vitamin C in diminishing the risk of cortical cataracts in women aged <60 y and for carotenoids in diminishing the risk of PSC cataracts in women who have never smoked.