Mycobacterium bovis infection in a dog.
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Animals↗
Biomedical subjects
S Davies
Publications and source records attributed to S Davies.
Elastic scattering spectroscopy accurately detects high grade dysplasia and cancer in Barrett's oesophagus.
BACKGROUND AND AIMS: Endoscopic surveillance of Barrett's oesophagus currently relies on multiple random biopsies. This approach is time consuming, has a poor diagnostic yield, and significant interobserver variability. Elastic scattering spectroscopy is a real time in vivo optical technique which detects changes in the physical properties of cells. The aim of this study was to assess the potential for elastic scattering to detect high grade dysplasia or cancer within Barrett's oesophagus. METHODS: Elastic scattering spectroscopy measurements collected in vivo were matched with histological specimens taken from identical sites within Barrett's oesophagus. All biopsies were reviewed by three gastrointestinal pathologists and defined as either "low risk" (non-dysplastic or low grade dysplasia) or "high risk" (high grade dysplasia or cancer). Two different statistical approaches (leave one out and block validation) were used to validate the model. RESULTS: A total of 181 matched biopsy sites from 81 patients, where histopathological consensus was reached, were analysed. There was good pathologist agreement in differentiating high grade dysplasia and cancer from other pathology (kappa = 0.72). Elastic scattering spectroscopy detected high risk sites with 92% sensitivity and 60% specificity and differentiated high risk sites from inflammation with a sensitivity and specificity of 79%. If used to target biopsies during endoscopy, the number of low risk biopsies taken would decrease by 60% with minimal loss of accuracy. A negative spectroscopy result would exclude high grade dysplasia or cancer with an accuracy of >99.5%. CONCLUSIONS: These preliminary results show that elastic scattering spectroscopy has the potential to target conventional biopsies in Barrett's surveillance saving significant endoscopist and pathologist time with consequent financial savings. This technique now requires validation in prospective studies.
Adenocarcinoma↗
Psoriasis management: considerations in women of childbearing age.
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Adult↗
The cervical smear test: does timing have an effect on sample adequacy?
OBJECTIVE: The aim of this study was to determine the effect of timing of the cervical smear test on sample adequacy. METHODS: Inadequate and negative smears from pre-menopausal women, with a regular menstrual cycle and who were not undertaking any hormone therapy, were selected and re-screened. The inadequate smears were then categorized according to the reasons for the inadequate result. The time of the cycle that the smear was taken was recorded for both inadequate and negative smears. The expected frequency of smears per phase was compared with the observed frequency per phase using the chi-squared statistical test. RESULTS: There was no significant difference between the overall observed and expected rate of the inadequate smears of nine general practitioner (GP) practices (P = 0.886), of GP practice 4 (lowest inadequate rate) (P = 0.610), or GP practice 6 (highest inadequate rate) (P = 0.621) at any phase of the cycle. CONCLUSION: Results show that there is no optimum phase for adequate sample collection, therefore it is suggested that there is no effect of timing of the cervical smear test on sample adequacy, that timing is not a relevant factor in reducing the inadequate smear rate, and restricting smear taking to mid-cycle is unnecessary. (The information regarding last menstrual period/length of cycle from which these conclusions were reached relied upon the accuracy of patient information given to the smear taker.).
Diagnostic Errors↗
Ultrasonographic diagnosis of unusual portal vascular abnormalities in two cats.
Two cases of ascites secondary to portal vascular abnormalities associated with portal hypertension are described. In the first case a five-month-old cat was presented with recurrent ascites and investigations showed that the underlying cause was a hepatic arteriovenous fistula. Ultrasonography showed direct communication of the coeliac artery and right branch of the portal vein. There was also hepatofugal flow in the main portal vein consistent with portal hypertension. The ultrasonographic features were similar to those seen in dogs with hepatic arteriovenous fistulae. In the second case, ascites, portal hypertension and an intraluminal mass in the main portal vein was diagnosed in a 16-year-old cat that had been presented with hyperthyroidism and hepatomegaly. Acquired portosystemic collaterals involving the left renal vein were present. Additional diagnostic investigations were not permitted. Ultrasonography was useful in both cases to document portal hypertension and the underlying cause.
Animals↗
Reminiscence therapy for dementia.
BACKGROUND: Reminiscence Therapy (RT) involves the discussion of past activities, events and experiences with another person or group of people, usually with the aid of tangible prompts such as photographs, household and other familiar items from the past, music and archive sound recordings. Reminiscence groups typically involve group meetings in which participants are encouraged to talk about past events at least once a week. Life review typically involves individual sessions, in which the person is guided chronologically through life experiences, encouraged to evaluate them, and may produce a life story book. Family care-givers are increasingly involved in reminiscence therapy. Reminiscence therapy is one of the most popular psychosocial interventions in dementia care, and is highly rated by staff and participants. There is some evidence to suggest it is effective in improving mood in older people without dementia. Its effects on mood, cognition and well-being in dementia are less well understood. OBJECTIVES: The objective of the review is to assess the effects of reminiscence therapy for older people with dementia and their care-givers. SEARCH STRATEGY: The trials were identified from a search of the Specialised Register of the Cochrane Dementia and Cognitive Improvement Group on 4 May 2004 using the term "reminiscence". The CDCIG Specialized Register contains records from all major health care databases (MEDLINE, EMBASE, PsycLIT, CINAHL) and many ongoing trials databases and is regularly updated. We contacted specialists in the field and also searched relevant Internet sites. We hand-searched Aging and Mental Health, the Gerontologist, Journal of Gerontology, Current Opinion in Psychiatry, Current Research in Britain: Social Sciences, British Psychological Society conference proceedings and Reminiscence database. SELECTION CRITERIA: Randomised controlled trials and quasi-randomized trials of reminiscence therapy for dementia. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data and assessed trial quality. MAIN RESULTS: Five trials are included in the review, but only four trials with a total of 144 participants had extractable data. The results were statistically significant for cognition (at follow-up), mood (at follow-up) and on a measure of general behavioural function (at the end of the intervention period). The improvement on cognition was evident in comparison with both no treatment and social contact control conditions. Care-giver strain showed a significant decrease for care-givers participating in groups with their relative with dementia, and staff knowledge of group members' backgrounds improved significantly. No harmful effects were identified on the outcome measures reported. AUTHORS' CONCLUSIONS: Whilst four suitable randomized controlled trials looking at reminiscence therapy for dementia were found, several were very small studies, or were of relatively low quality, and each examined different types of reminiscence work. Although there are a number of promising indications, in view of the limited number and quality of studies, the variation in types of reminiscence work reported and the variation in results between studies, the review highlights the urgent need for more and better designed trials so that more robust conclusions may be drawn.
Aged↗
Psychopathology in children with epilepsy before and after temporal lobe resection.
The aim of this study was to establish the rate and spectrum of psychiatric disorder among children before and after temporal lobe surgery for epilepsy. Data were examined for associations between psychopathology and seizure outcome following surgery, or association between psychopathology and other variables, such as laterality of lesion, sex, cognitive level, and underlying pathology. Participants were 60 children (35 males, 25 females) who had focal seizures of temporal lobe origin and who had undergone temporal lobe resection between 1992 and 1998; mean age at time of operation 10 y 7 mo, (SD 4 y 11 mo) range 7 mo to 17 y 11 mo. Mean length of follow-up was 5.1 years (SD 2.3, range 2 to 10 y). Twenty-eight (47%) children had undergone right temporal lobectomy. Diagnosis of a psychiatric disorder was present in 50/60 (83%) children at some point, with high rates of psychiatric comorbidity. Common childhood psychiatric disorders of attention-deficit-hyperactivity disorder, oppositional defiant disorder/conduct disorder, and emotional disorders were present in about 25% of children. Disorders rarely seen in the general child population were over-represented: disruptive behaviour disorder--not otherwise specified (30/60 [50%]), and pervasive developmental disorder (autistic spectrum disorder; 23/60 [38%]). there was no significant relationship between pathology, sex, seizure frequency, or postoperative seizure outcome and psychiatric disorder, other than for pervasive developmental disorder. The same proportion of children had psychiatric diagnoses pre- and postoperatively (43/60 [72%] and 41/57 [72%] respectively). Although mental health problems are common in children undergoing temporal lobe resection, there are few predictors of psychiatric outcome following epilepsy surgery. Parents require counselling on these issues in the preoperative work-up.
Adolescent↗
"Contact A Family": professionals and parents in partnership.
This paper considers the evidence base on the role of parent organisations in meeting the needs of parents of disabled children for information and support. Having a disabled child is a major cause of stress and has an impact on the health and wellbeing of the entire family. Current concepts of stress and coping are used to consider coping strategies, including the search for information, the desire to stay in control, and the quest for social support. How and when information and support are provided will impact on how well the family adjust and cope.
Adaptation, Psychological↗
Diagnosis of myocarditis by cardiovascular magnetic resonance.
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Adult↗
Multiple mechanisms are implicated in the generation of 5q35 microdeletions in Sotos syndrome.
BACKGROUND: Sotos syndrome is characterised by learning difficulties, overgrowth, and a typical facial appearance. Microdeletions at 5q35.3, encompassing NSD1, are responsible for approximately 10% of non-Japanese cases of Sotos. In contrast, a recurrent approximately 2 Mb microdeletion has been reported as responsible for approximately 50% of Japanese cases of Sotos. METHODS: We screened 471 cases for NSD1 mutations and deletions and identified 23 with 5q35 microdeletions. We investigated the deletion size, parent of origin, and mechanism of generation in these and a further 10 cases identified from published reports. We used "in silico" analyses to investigate whether repetitive elements that could generate microdeletions flank NSD1. RESULTS: Three repetitive elements flanking NSD1, designated REPcen, REPmid, and REPtel, were identified. Up to 18 cases may have the same sized deletion, but at least eight unique deletion sizes were identified, ranging from 0.4 to 5 Mb. In most instances, the microdeletion arose through interchromosomal rearrangements of the paternally inherited chromosome. CONCLUSIONS: Frequency, size, and mechanism of generation of 5q35 microdeletions differ between Japanese and non-Japanese cases of Sotos. Our microdeletions were identified from a large case series with a broad range of phenotypes, suggesting that sample selection variability is unlikely as a sole explanation for these differences and that variation in genomic architecture might be a contributory factor. Non-allelic homologous recombination between REPcen and REPtel may have generated up to 18 microdeletion cases in our series. However, at least 15 cannot be mediated by these repeats, including at least seven deletions of different sizes, implicating multiple mechanisms in the generation of 5q35 microdeletions.
Abnormalities, Multiple↗
Sequences in drug discovery.
Sequences in Drug Discovery is a new series of distinct brief reports on breaking topics in the field of drug R&D. This month's Sequences in Drug Discovery contains the following reports: Spotlight on West Nile virus vaccines. p38alpha MAPK--a dynamic target in rheumatoid arthritis. The need for new contraceptives: targeting PDE3. Vasopeptidase inhibition with a triple mode of action. Current advances in the development of 5-HT(6) receptor antagonists.
3',5'-Cyclic-AMP Phosphodiesterases↗
Tolbutamide potentiates the volume-regulated anion channel current in rat pancreatic beta cells.
AIMS/HYPOTHESIS: Hypoglycaemic sulphonylureas are thought to stimulate insulin release by binding to a sulphonylurea receptor, closing K(ATP) channels and inducing electrical activity. However, the fact that these drugs stimulate insulin release at high glucose concentrations where K(ATP) channels are closed suggests additional ionic actions. The aim of this study was to test the hypothesis that sulphonylureas influence the current of the glucose- and volume-regulated anion channel. METHODS: Electrical and ion-channel activity were recorded in isolated rat beta cells using the patch-clamp technique. (86)Rb(+) efflux was measured using intact islets. Beta cell volume was measured using a video-imaging technique. RESULTS: In the absence of glucose, tolbutamide (100 micromol/l) transiently depolarised the cells. In the presence of glucose (5 mmol/l), tolbutamide evoked a sustained period of electrical activity, whilst at 10 mmol/l glucose, the drug evoked a pronounced 'silent' depolarisation. In the absence of glucose, tolbutamide inhibited (86)Rb(+) efflux. However, at 10 mmol/l glucose, tolbutamide induced a transient stimulation of efflux. Tolbutamide potentiated the whole-cell volume-regulated anion conductance in a glucose-dependent manner with an EC(50) of 85 micromol/l. In single channel recordings, tolbutamide increased the channel-open probability. Tolbutamide caused beta cell swelling in the presence of glucose, but not in its absence. CONCLUSIONS/INTERPRETATION: Tolbutamide can induce beta cell electrical activity by potentiating the glucose- and volume-regulated anion channel current. This effect is probably not due to a direct effect of the drug on the channel, but could be secondary to a metabolic action in the beta cell.
4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
Progesterone inhibits insulin-like growth factor binding protein-1 (IGFBP-1) production by explants of the Fallopian tube.
The Fallopian tube provides the environment for early embryo growth, a process which is influenced by insulin-like growth factors (IGFs) in the tubal fluid. Whether the bioavailability of tubal IGFs is modulated by locally produced IGF-binding protein (IGFBP-1) is not clear. An explant culture system from human Fallopian tube mucosa was, therefore, developed enabling the potential for IGFBP-1 production by this tissue to be examined directly. Initial characterization of the system established that the explants maintained responsiveness to steroids. Thus, oviduct-specific glycoprotein production, a major product of the oviduct in vivo, continued to be made via an estrogen-sensitive pathway in the culture. The presence of mRNA for IGFBP-1 was established within the explants by the use of quantitative RT-PCR and IGFBP-1 protein was measured by enzyme-linked immunosorbent assay. Although insulin and estradiol had no consistent effect on IGFBP-1, addition of progesterone had a significant inhibitory effect on IGFBP-1 production, both at the mRNA and protein levels. A dose-range of progesterone revealed an incremental inhibitory effect of progesterone on IGFBP-1 output (maximal effect, 25-50 nmol/l), consistent with physiological inhibition of this process during the luteal phase. We suggest that progesterone might, therefore, play a role in controlling the bioavailability of IGFs to the embryo during early development within the Fallopian tube.
Adult↗
Improvement in quality of life of children with acute Crohn's disease does not parallel mucosal healing after treatment with exclusive enteral nutrition.
BACKGROUND: Crohn's disease is a chronic debilitating disorder affecting a child's physical and emotional well-being. Recent emphasis on 'quality of life' (QOL) has led to re-evaluation of available medical treatments. AIM: To assess prospectively change in QOL, clinical disease activity and intestinal mucosal inflammation in active paediatric Crohn's disease after treatment with exclusive enteral nutrition. In addition, we evaluated whether change in QOL could predict changes in paediatric Crohn's disease activity index (PCDAI) and mucosal inflammation (endoscopic and histologic). METHODS: The IMPACT II questionnaire was used prospectively and longitudinally in 26 consecutively recruited children [16 males (67%), median 14 years, s.d. = 1.7 years] with active Crohn's disease (PCDAI > 20). They were treated with a new polymeric enteral feed (ACD004, Nestle) for a period of 8 weeks. All had PCDAI, QOL and endoscopic assessment at the time of diagnosis and after 8 weeks of treatment. RESULTS: Twenty-three of 26 children achieved a clinical remission at 8 weeks, with improvement in the QOL scores (P < 0.05). The change in QOL score after treatment was predictive of achieving a clinical remission, but not of histological improvement. CONCLUSIONS: Although children may find dietary restrictions difficult, this study confirms a clear improvement in QOL after treatment with exclusive enteral nutrition. However, improvement in QOL scores is not reflected by improvement in mucosal inflammation. Whilst improving QOL remains a core principal in patient management, the long-term consequences of ongoing mucosal inflammation must be better understood before relying only on short-term QOL measures to dictate treatment choices.
Acute Disease↗
Effectiveness of preoperative staging in rectal cancer: digital rectal examination, endoluminal ultrasound or magnetic resonance imaging?
In rectal cancer, preoperative staging should identify early tumours suitable for treatment by surgery alone and locally advanced tumours that require therapy to induce tumour regression from the potential resection margin. Currently, local staging can be performed by digital rectal examination (DRE), endoluminal ultrasound (EUS) or magnetic resonance imaging (MRI). Each staging method was compared for clinical benefit and cost-effectiveness. The accuracy of high-resolution MRI, DRE and EUS in identifying favourable, unfavourable and locally advanced rectal carcinomas in 98 patients undergoing total mesorectal excision was compared prospectively against the resection specimen pathological as the gold standard. Agreement between each staging modality with pathology assessment of tumour favourability was calculated with the chance-corrected agreement given as the kappa statistic, based on marginal homogenised data. Differences in effectiveness of the staging modalities were compared with differences in costs of the staging modalities to generate cost effectiveness ratios. Agreement between staging and histologic assessment of tumour favourability was 94% for MRI (kappa=0.81, s.e.=0.05; kappa(W)=0.83), compared with very poor agreements of 65% for DRE (kappa=0.08, s.e.=0.068, kappa(W)=0.16) and 69% for EUS (kappa=0.17, s.e.=0.065, kappa(W)=0.17). The resource benefits resulting from the use of MRI rather than DRE was 67164 UK pounds and 92244 UK pounds when MRI was used rather than EUS. Magnetic resonance imaging dominated both DRE and EUS on cost and clinical effectiveness by selecting appropriate patients for neoadjuvant therapy and justifies its use for local staging of rectal cancer patients.
Adult↗
Primary synovial sarcoma of the pleura: beware of misdiagnosis.
Primary synovial sarcoma of the pleura is an uncommon entity in the present medical literature. However, the paucity of documented cases may be due to misdiagnoses as a malignant mesothelioma in the past. Early diagnosis with new molecular techniques may improve the outcome of this tumour, which is believed to have a grave prognosis at present.
Journal Article↗
Donor DNA in a renal cell carcinoma metastasis from a bone marrow transplant recipient.
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Bone Marrow Transplantation↗
An investigation into effects of long-distance seed dispersal on organelle population genetic structure and colonization rate: a model analysis.
A simulation-based modelling approach is used to examine the effects of stratified seed dispersal (representing the distribution of the majority of dispersal around the maternal parent and also rare long-distance dispersal) on the genetic structure of maternally inherited genomes and the colonization rate of expanding plant populations. The model is parameterized to approximate postglacial oak colonization in the UK, but is relevant to plant populations that exhibit stratified seed dispersal. The modelling approach considers the colonization of individual plants over a large area (three 500 km x 10 km rolled transects are used to approximate a 500 km x 300 km area). Our approach shows how the interaction of plant population dynamics with stratified dispersal can result in a spatially patchy haplotype structure. We show that while both colonization speeds and the resulting genetic structure are influenced by the characteristics of the dispersal kernel, they are robust to changes in the periodicity of long-distance events, provided the average number of long-distance dispersal events remains constant. We also consider the effects of additional physical and environmental mechanisms on plant colonization. Results show significant changes in genetic structure when the initial colonization of different haplotypes is staggered over time and when a barrier to colonization is introduced. Environmental influences on survivorship and fecundity affect both the genetic structure and the speed of colonization. The importance of these mechanisms in relation to the postglacial spread and genetic structure of oak in the UK is discussed.
Climate↗