Colon capsule endoscopy.

There are multiple indications for luminal imaging of the colon. From assessment of known disease, to diagnosing new pathology; intra-luminal visualisation is the mainstay of gastrointestinal diagnosis. Colonoscopy and radiological imaging are currently the most frequently deployed diagnostic methods. However, both have an associated risk profile, have significant resource pressures and are not universally tolerated. Colon capsule endoscopy (CCE) offers an adjunct to these diagnostic options. In this narrative review the utility of CCE is described. Its current uses, potential benefits and future developments are also discussed.

Disconnections in personal neglect.

Personal neglect is a disorder in the perception and representation of the body that causes the patients to behave as if the contralesional side of their body does not exist. This clinical condition has not been adequately investigated in the past as it has been considered a symptom of unilateral spatial neglect, which has mainly been studied with reference to extrapersonal space. Only a few studies with small samples have investigated the neuroanatomical correlates of personal neglect, and these have mainly focused on discrete cortical lesions and modular accounts, as well as being based on the hypothesis that this disorder is associated with somatosensory and spatial deficits. In the present study, we tested the novel hypothesis that personal neglect may be associated not only with discrete cortical and subcortical lesions, but also with disconnections of white matter tracts. We performed an advanced lesion analyses in a large sample of 104 right hemisphere damaged patients, 72 of whom were suffering from personal neglect. Results from the analyses of the grey and white matter were controlled for co-occurrent clinical variables such as extrapersonal neglect, anosognosia for hemiplegia and motor deficits, along with other lesion-related variables such as lesion size and the interval from the lesion onset to neuroimaging recordings. Our results reveal that personal neglect is associated with lesions in a medial network which involves the temporal cortex (Heschl's gyrus), the ventro-lateral nuclei of the thalamus and the fornix. This suggests that personal neglect involves a convergence between sensorimotor processes, spatial representation and the processing of self-referred information (episodic memory).

Temporal Trends in Surgical Resection Rates and Biologic Prescribing in Crohn's Disease: A Population-based Cohort Study.

BACKGROUND: The use of biologic therapy for Crohn's disease [CD] continues to evolve, however, the effect of this on the requirement for surgery remains unclear. We assessed changes in biologic prescription and surgery over time in a population-based cohort. METHODS: We performed a retrospective cohort study of all 1753 patients diagnosed with CD in Lothian, Scotland, between January 1, 2000 and December 31, 2017, reviewing the electronic health record of each patient to identify all CD-related surgery and biologic prescription. Cumulative probability and hazard ratios for surgery and biologic prescription from diagnosis were calculated and compared using the log-rank test and Cox regression analysis stratified by year of diagnosis into cohorts. RESULTS: The 5-year cumulative risk of surgery was 20.4% in cohort 1 [2000-2004],18.3% in cohort 2 [2005-2008], 14.7% in cohort 3 [2009-2013], and 13.0% in cohort 4 [2014-2017] p <0.001. The 5-year cumulative risk of biologic prescription was 5.7% in cohort 1, 12.2% in cohort 2, 22.0% in cohort 3, and 44.9% in cohort 4 p <0.001. CONCLUSIONS: The increased and earlier use of biologic therapy in CD patients corresponded with a decreasing requirement for surgery over time within our cohort. This could mean that adopting a top-down or accelerated step-up treatment strategy may be effective at reducing the requirement for surgery in newly diagnosed CD.

Faecal Calprotectin and Magnetic Resonance Enterography in Ileal Crohn's Disease: Correlations Between Disease Activity and Long-Term Follow-Up.

BACKGROUND AND AIMS: Magnetic resonance enterography [MRE] is the gold standard for assessing ileal inflammation in Crohn's disease [CD]. The aim of the present study was to correlate faecal calprotectin [FC] to MRE via a simple score in an exclusive ileal cohort with long-term follow-up for association with time to surgery or biologic therapy. METHODS: In total, 150 MRE studies with matched FC [±30 days] were identified from the Edinburgh FC Register [2008-12; n = 18138]. Scans were re-read blinded to clinical data, independently, by two expert gastrointestinal radiologists, to generate a simple MRE score [range 0-10] from assessment of the worst intestinal segment plus total disease extent. RESULTS: In total, 119 MRE scans were evaluated from 104 patients with ileal CD [L1 or L3 with panproctocolectomy]. Receiver operating characteristic analysis showed an area under the curve of 0.77 [0.67-0.87, p < 0.0001] for FC and MRE score >1, with an optimal cut-off of 145 µg/g for severe inflammation on MRE with 69.3% [57.6-79.5] sensitivity and 71.4% [53.7-85.4] specificity. Long-term follow-up over a median [interquartile range] of 2086 days [1786-2353] revealed FC ≥ 145 µg/g was associated with reduced biologic-free survival until 3 years following MRE, whereas MRE score [severe vs absent] was associated with reduced surgery- and biologic-free survival throughout follow-up. Backwards stepwise logistic regression revealed that length of ileal disease (odds ratio [OR] 3.8, 1.1-13.2, p = 0.034) and increased bowel wall thickness at MRE [OR 4.2, 1.6-10.7, p < 0.0001] or female sex [OR 5.2, 1.5-18.7, p = 0.011] increased the risk of biologic use or surgery, respectively. CONCLUSIONS: FC correlates well with MRE assessment of ileal CD with MRE parameters associated with long-term biologic- and surgery-free remission.

Real-world Effectiveness and Safety of Vedolizumab for the Treatment of Inflammatory Bowel Disease: The Scottish Vedolizumab Cohort.

BACKGROUND & AIMS: Vedolizumab is an anti-a4b7 monoclonal antibody that is licensed for the treatment of moderate to severe Crohn's disease and ulcerative colitis. The aims of this study were to establish the real-world effectiveness and safety of vedolizumab for the treatment of inflammatory bowel disease. METHODS: This was a retrospective study involving seven NHS health boards in Scotland between June 2015 and November 2017. Inclusion criteria included: a diagnosis of ulcerative colitis or Crohn's disease with objective evidence of active inflammation at baseline (Harvey-Bradshaw Index[HBI] ≥5/Partial Mayo ≥2 plus C-reactive protein [CRP] >5 mg/L or faecal calprotectin ≥250 µg/g or inflammation on endoscopy/magnetic resonance imaging [MRI]); completion of induction; and at least one clinical follow-up by 12 months. Kaplan-Meier survival analysis was used to establish 12-month cumulative rates of clinical remission, mucosal healing, and deep remission [clinical remission plus mucosal healing]. Rates of serious adverse events were described quantitatively. RESULTS: Our cohort consisted of 180 patients with ulcerative colitis and 260 with Crohn's disease. Combined median follow-up was 52 weeks (interquartile range [IQR] 26-52 weeks). In ulcerative colitis, 12-month cumulative rates of clinical remission, mucosal healing, and deep remission were 57.4%, 47.3%, and 38.5%, respectively. In Crohn's disease, 12-month cumulative rates of clinical remission, mucosal healing, and deep remission were 58.4%, 38.9%, and 28.3% respectively. The serious adverse event rate was 15.6 per 100 patient-years of follow-up. CONCLUSIONS: Vedolizumab is a safe and effective treatment for achieving both clinical remission and mucosal healing in ulcerative colitis and Crohn's disease.

Variability in chromosome aberrations, sister chromatid exchanges, and mitogen-induced blastogenesis in peripheral lymphocytes from control individuals.

Confidence in results from monitoring genetic end points in environmentally or occupationally exposed individuals can be improved with knowledge of the normal variability of changes in genetic end points in the general population. Confounding effects can be determined, and study interpretation can be improved by correlation of this variability with various lifestyle factors such as sex and age, smoking and drinking habits, viral infections, exposure to diagnostic X-rays, etc. Eight blood samples were taken from each of 24 male and 24 female volunteers over a period of 2 years. Questionnaires pertaining to lifestyle were completed at the time of each sampling. Whole blood was cultured and slides prepared for chromosome aberration (CA) or sister chromatid exchange (SCE) analysis. Separated mononuclear cells were cultured with a range of phytohemagglutinin concentrations, and the maximum level of mitogen-induced blastogenesis was determined by measurement of [3H]thymidine uptake. There was a significant effect of both year and season of sampling for all three end points. Because there was no consistent pattern in 2 successive years, effects were thought to be independent of season. No significant effects in any of the three end points were found with respect to sex or age nor any of the other lifestyle factors, although SCE frequency and mitogen-induced blastogenesis were nearly always higher in females than in males. These results point to the need for concurrent sampling of controls with exposed populations.

Malformed foetuses and karyotype abnormalities in the offspring of cyclophosphamide and allyl alcohol-treated male rats.

Litters sired by male rats chronically treated with cyclophosphamide (CP) or allyl alcohol (AA), were evaluated for the incidence of foetal malformations and karyotype abnormalities. The male rats were also examined for the induction of deleterious effects on various parameters including those involved in reproductive performance. A highly significant and consistent increase in the numbers of malformed foetuses was seen in the litters from CP-treated male rats. Chromosome preparations revealed that a large proportion of the malformed foetuses carried karyotypic abnormalities. These effects were paralleled by a large increase in the number of post-implantation losses without significant differences in several sperm and semen characteristics including sperm abnormalities. No adverse reproductive effects were observed with allyl alcohol treatment.

The use of a battery of strains of mice in a factorial design to study the induction of dominant lethal mutations.

The induction of dominant lethality following oral dosing of males with 200 mg/kg of cyclophosphamide was investigated using a factorial experimental design. Males from 3 genotypes, BALB/c, CBA/Ca and CBA/Ca X C57BL/6JF1 hybrid (CBB6F1) were mated to 6 females of the same genotype as the males over 3 weeks. Cyclophosphamide reduced the mating frequency of the BALB/c and CBA/Ca males. The total number of implants/female was reduced in all 3 genotypes with the greatest effect in the first 2 weeks after the males were treated. The proportion of early deaths/litter was significantly increased in CBA/Ca and CBB6F1 but the increase was smaller and non-significant with BALB/c. There was a high incidence (29.8%) of early deaths in the control BALB/c females. Statistical analysis of the ratio of early deaths to total implants in a litter using either the Freeman-Tukey binomial or the arc-sine transformation gave similar and satisfactory results. Analysis of early death data rather then the ratio of early deaths: total implants would have led to misleading conclusions. The implications of the use of a factorial design in dominant lethal assays for the detection of strain variation in mutagenic response without an increase in animal usage is discussed.

Increased incidence of abnormal foetuses in the offspring of cyclophosphamide-treated male mice.

The incidence of morphologically abnormal foetuses in the litters of cyclophosphamide (CP)-treated male mice was investigated and compared with control values. In two experiments (100 mg/kg) CP was shown to increase the incidence of grossly abnormal foetuses over that seen in the controls, although neither was statistically significant in isolation. When the probabilities from the two tests of significance were combined using the method of Fisher the result was significant (P = 0.02). These results suggest that an acute exposure to a mutagen in male mice can cause genetic damage that results in an increased incidence of phenotypically abnormal offspring. However, the large numbers of animals required and the variable control level of abnormalities, indicate that this dosing regimen is an inefficient method of studying the genetic mechanisms responsible for the effects seen.

Variation in sister-chromatid exchange among 106 members of the general U.K. population.

SCE scores of lymphocytes from 106 people revealed that the majority of background variation in SCE was between cells within individuals. Highly significant differences existed between individuals. Lesser, but still highly significant differences also existed between replicate cultures. Inter-individual variation was contributed to by each person's sex and their smoking habits. SCE frequency was not influenced by any of the other factors considered, age, drinking habits and diagnostic X-ray exposure of persons or lymphocyte number and proliferation rate in cultures.

The protective effects of L-ascorbic acid and DL-alpha-tocopherol on cultured rat embryos treated with xanthine/xanthine oxidase.

Abnormalities of the neural suture were observed in cultured rat embryos exposed to oxygen radicals generated by xanthine and xanthine oxidase. The distribution of the severity of these abnormalities was altered by the addition of L-ascorbic acid (AA) or DL-alpha-tocopherol (AT). The antioxidant effect of AA and AT were probably responsible for the protection of the embryos from the damaging effects of oxygen radicals.

Metaphase analysis of human lymphocytes treated with 4-chloromethylbiphenyl and benzyl chloride.

4CMB and BC caused mitotic inhibition in human lymphocytes at low doses (greater than 20 and greater than 10 microgram/ml respectively). At non-inhibitory concentrations, neither substance produced increases in cells with breaks or breaks per cell, although 4CMB did induce a significant increase in gaps at dose. 4CMB and BC are not chromosome mutagens in this system.

Sister-chromatid exchanges in human lymphocytes treated with 4-chloromethylbiphenyl and benzyl chloride.

At non-inhibitory concentrations, 4CMB and BC both induced small, but dose-related increases in SCE. The dose-response curves gave a highly significant correlation for 4CMB (r = 0.996, P less than 0.001) and a significant correlation for BC (r = 0.757, P less than 0.05) which reflects the relative activities of these substances in bacterial mutation tests.

Chromosome aberrations (CA), sister-chromatid exchanges (SCE) and mitogen-induced blastogenesis in cultured peripheral lymphocytes from 48 control individuals sampled 8 times over 2 years.

Confidence in the measurement of positive effects determined by monitoring of environmentally or occupationally exposed individuals can be enhanced by a knowledge of the normal variability in these endpoints in the general population. Confounding effects can be determined and study interpretation improved by correlation of this variability with various lifestyle factors such as sex and age of donor, smoking and drinking habits, viral infections, exposure to diagnostic X-rays, etc. 8 blood samples were taken from each of 24 male and 24 female volunteers over a period of 2 years. Questionnaires pertaining to lifestyle were completed at the time of each sampling. Whole blood was cultured and slides prepared for CA or SCE analysis. Separated mononuclear cells were cultured with a range of phytohaemagglutinin concentrations and the maximum level of mitogen-induced blastogenesis was determined by measurements of [3H]thymidine uptake. There was a significant effect of both year and season of sampling for all 3 endpoints. No significant effects in any of the 3 endpoints were found with respect to sex or age of donor nor any of the other lifestyle factors, although SCE frequency and mitogen-induced blastogenesis were nearly always higher in females than males. These results point to the need for concurrent sampling of controls with exposed populations.

Tumours and malformations in the adult offspring of cyclophosphamide-treated and control male rats--preliminary communication.

Adult offspring aged 52-104 weeks, from male Sprague-Dawley rats treated chronically with cyclophosphamide (CP) were examined for tumours and gross abnormalities. Litter size at birth and at weaning was found to be greatly reduced as a result of paternal CP treatment. No unusual abnormalities were found at post-mortem examination but there was an increase in the incidence of hydronephrosis in offspring from CP-treated males compared with offspring from control males. This increase could have been indirectly caused by CP-treatment through reduced litter size. Histological examination of 26 tumours showed a variety of tumour types in the offspring of CP-treated and control males. Two of the four uterine tumours in offspring from CP-treated males were examined histologically; one was a sarcoma and the other an adenocarcinoma. Although no uterine tumours were found in offspring from control males, it is not clear whether this difference in frequency was treatment-related. The most common tumour site in female offspring from both CP-treated and control males was the mammary gland, and all six of these tumours which were examined histologically were adenofibromas. Abnormal karyotypes were observed in 2 out of 21 offspring showing abnormalities from CP-treated males and none out of 2 offspring with abnormalities from control males. These were not associated with tumours. It was concluded from this limited study that there was no clear evidence of increased tumour incidence in the offspring from CP-treated males. There was an indication that abnormal karyotypes may have been caused by the paternal CP treatment and these abnormalities persisted into adulthood.

Chromosome aberrations, mitogen-induced blastogenesis and proliferative rate index in peripheral lymphocytes from 106 control individuals of the U.K. population.

Blood samples were taken from 106 individuals (73 males and 33 females) and examined for chromosome aberrations, mitogen-induced blastogenesis and proliferative rate index (PRI). The values obtained were investigated in relation to sex, age, smoking, alcohol consumption and X-ray exposure. In all the parameters, there was shown to be a difference between the mean values for the males and females. The incidence of chromosome aberrations was greater in females than in the males, whereas the mean values of PRI and mitogen-induced blastogenesis were lower in females than in the males. A sex difference has been reported previously in the same population, in that the females were shown to have a higher rate of sister-chromatid exchanges than the males (Anderson et al., 1986; Dewdney et al., 1986). Contraceptive pill usage was not considered to be of importance in the sex difference seen and there was shown to be no significant influence due to age, smoking or alcohol consumption on any of the parameters except that smoking reduced lymphocyte PRI. Males with previous X-ray exposure also showed a lower response to mitogen-induced blastogenesis and had a reduced PRI.

A cognitive neuropsychological and psychophysiological investigation of a patient who exhibited an acute exacerbated behavioural response during innocuous somatosensory stimulation and movement.

We report findings from a cognitive neuropsychological and psychophysiological investigation of a patient who displayed an exacerbated acute emotional expression during movement, innocuous, and aversive somatosensory stimulation. The condition developed in the context of non-specific white matter ischaemia along with abnormalities in the cortical white matter of the left anterior parietal lobe, and subcortical white matter of the left Sylvian cortex. Cognitive neuropsychological assessment revealed a pronounced deficiency in executive function, relative to IQ, memory, attention, language and visual processing. Compared to a normal control group, the patient [EQ] displayed a significantly elevated skin conductance level during both innocuous and aversive somatosensory stimulation. His pain tolerance was also significantly reduced. Despite this, EQ remained able to accurately describe the form of stimulation taking place, and to rate the levels of pain intensity and pain affect. These results suggest that EQ's exaggerated behavioural response and reduced pain tolerance to somatosensory stimulation may be linked to cognitive changes, possibly related to increased apprehension and fear, rather than altered pain intensity or pain affect per se.

Progressive, reversible sensorineural hearing loss caused by azathioprine.

OBJECTIVE: This paper describes the first reported case of progressive sensorineural hearing loss caused by azathioprine, which was reversed on stoppage of the drug. CASE REPORT: A female patient with previously normal hearing presented with progressive sensorineural hearing loss after being started on azathioprine. Otological and neurological examination findings were unremarkable. After stopping the drug, the patient reported an improvement in hearing, which was confirmed on pure tone audiometry. CONCLUSION: This previously unreported side effect of azathioprine is highlighted in order to increase clinical awareness. Early recognition of this adverse effect is important to minimise the possibility of permanent sensorineural hearing loss.

Modified use of Kocher's dissector in ligation of the superior thyroid pedicle.

BACKGROUND: More than a century has passed since Emil Theodor Kocher first described the use of 'Kocher's thyroid dissector' to secure the superior thyroid pedicle. METHOD: Despite the technological advances in thyroid surgery, the dissector remains an extremely useful instrument. This paper describes a modified use of the dissector, and reports on how this facilitates safer and easier surgery. RESULTS AND CONCLUSION: Application of this simple, modified technique can improve the safety and efficiency of thyroid surgery, with negligible financial outlay.

Effect of eyespot caused by Oculimacula yallundae and O. acuformis, assessed visually and by competitive PCR, on stem strength associated with lodging resistance and yield of winter wheat.

Winter wheat, (cv. Consort) was inoculated with three isolates of either Oculimacula yallundae or O. acuformis to determine the effect of eyespot caused by each species on yield and lodging resistance of winter wheat. Plants were visually assessed for disease incidence and severity, and pathogen DNA was quantified at GS 33 and GS 60. At early milk development of the crop (GS 72), 900 main shoots were also visually assessed for the disease and subjected to mechanical tests for stem strength. Pathogen DNA was extracted from each shoot and quantified using competitive polymerase chain reaction (PCR). Although slight and moderate eyespot lesions caused by either species had no effect on ear weight, severe lesions caused by O. acuformis and O. yallundae reduced ear weight by 3% and 7%, respectively. Stem lodging failed to occur at the site; however, yield losses of 11% for O. acuformis and 6% for O. yallundae were observed. Visual assessment failed to reveal differences between species in their effect on plant characteristics, stem bending strength, or stem safety factor. PCR data, however, showed that the two species had similar effects determined by different DNA concentrations. Both species reduced lodging resistance (stem safety factor) compared with the control. In contrast to healthy plants, where reductions were related predominantly to the height and weight distribution of the plants, the observed reductions of stem lodging resistance in infected plants with Oculimacula spp. were associated primarily with reductions in stem bending strength.