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Biomedical subjects

M Dennis

Publications and source records attributed to M Dennis.

At least 19 recordsLinked to original sources
PubMed2006

Further evidence that the KIAA0319 gene confers susceptibility to developmental dyslexia.

The DYX2 locus on chromosome 6p22.2 is the most replicated region of linkage to developmental dyslexia (DD). Two candidate genes within this region have recently been implicated in the disorder: KIAA0319 and DCDC2. Variants within DCDC2 have shown association with DD in a US and a German sample. However, when we genotyped these specific variants in two large, independent UK samples, we obtained only weak, inconsistent evidence for their involvement in DD. Having previously found evidence that variation in the KIAA0319 gene confers susceptibility to DD, we sought to refine this genetic association by genotyping 36 additional SNPs in the gene. Nine SNPs, predominantly clustered around the first exon, showed the most significant association with DD in one or both UK samples, including rs3212236 in the 5' flanking region (P = 0.00003) and rs761100 in intron 1 (P = 0.0004). We have thus refined the region of association with developmental dyslexia to putative regulatory sequences around the first exon of the KIAA0319 gene, supporting the presence of functional mutations that could affect gene expression. Our data also suggests a possible interaction between KIAA0319 and DCDC2, which requires further testing.

5' Untranslated Regions↗
PubMed2006

Self harm and attempted suicide in adults: 10 practical questions and answers for emergency department staff.

Self harm is a complex behaviour that can be best thought of as a maladaptive response to acute and chronic stress, often but not exclusively linked with thoughts of dying. Patients presenting with self harm usually have current psychosocial difficulties, are likely to be suffering from mental health problems, and are at significant risk of further self harm and suicide. Recent guidelines suggest that all self harm attendees should receive an initial risk assessment at triage in the emergency department. A more detailed mental health assessment and an assessment of psychological and social needs should then be performed by trained staff, ideally specialist mental professionals experienced in this area. Risk of subsequent suicide is particularly high in those with high unresolved suicidal intent, depressive disorder, chronic alcohol and drug misuse, social isolation, and current physical illness. Patients with one or more of these risk factors should be offered enhanced care that may include inpatient or outpatient follow up care, a list of local support resources, and, where possible, self help material. Frequent repeaters, those with alcohol and substance use problems, those with physical or mental illness, and those who are isolated also require input from specialist mental health professionals. It is also recommended that adolescents and elderly people warrant a mandatory specialist assessment.

Adult↗
PubMed2006

FOOD: a multicentre randomised trial evaluating feeding policies in patients admitted to hospital with a recent stroke.

OBJECTIVES: To determine whether routine oral nutritional supplementation of a normal hospital diet improves outcome after stroke (Trial 1); whether early tube feeding improves the outcomes of dysphagic stroke patients (Trial 2); and if tube feeding via a percutaneous endoscopic gastrostomy (PEG) results in better outcomes than that via a nasogastric tube (NG) (Trial 3). DESIGN: The Feed Or Ordinary Diet (FOOD) trial was a family of three pragmatic, randomised controlled trials (RCTs). They shared facilities for randomisation, data collection, follow-up and coordination. Patients could be co-enrolled in more than one of these trials. SETTING: Patients were enrolled in 131 hospitals in 18 countries. PARTICIPANTS: A total of 5033 patients who had been admitted to hospital with a recent stroke were enrolled in the trials between November 1996 and July 2003. INTERVENTIONS: In Trial 1, patients who could swallow within the first 30 days of admission were allocated to normal hospital diet versus normal hospital diet plus oral nutritional supplements (equivalent to 360 ml of 1.5 kcal/ml, 20 g of protein per day) until hospital discharge. In Trial 2, dysphagic patients enrolled within 7 days of admission were allocated to early enteral tube feeding versus avoid any enteral tube feeding for at least 1 week. In Trial 3, dysphagic patients were allocated within 30 days of admission to receive enteral tube feeding via PEG versus NG. MAIN OUTCOME MEASURES: Survival and the modified Rankin scale (MRS), a measure of functional outcome (grade 0 indicating no symptoms and grade 5 indicating severe disability, requiring help day and night). The primary outcomes were measured 6 months after enrollment, blind to treatment allocation, by the patient or their proxy completing a postal or telephone questionnaire. RESULTS: In Trial 1, 4023 patients were enrolled by 125 hospitals in 15 countries. Only 314 (7.8%) patients were judged undernourished at baseline. Vital status and MRS at the end of the trial were known for 4012 (99.7%) and 4004 (99.5%), respectively. Of the 2007 allocated normal hospital diet, 253 (12.6%) died, 918 (45.7%) were alive with poor outcome (MRS 3-5) and 823 (41.1%) had a good outcome (MRS 0-2). Of the 2016 allocated oral supplements, 241 (12.0%) died, 953 (47.3%) were alive with poor outcome and 813 (40.4%) had a good outcome. The supplemented diet was associated with an absolute reduction in risk of death of 0.7% (95% CI -1.4 to 2.7; p = 0.5) and a 0.7% (95% CI -2.3 to 3.8, p = 0.6) increased risk of death or poor outcome. In Trial 2, a total of 859 patients were enrolled by 83 hospitals in 15 countries. MRS at the end of the trial was known for 858 (99.9%). At follow-up, of 429 allocated early tube feeding, 182 (42.4%) died, 157 (36.6%) were alive with poor outcome (MRS 4-5) and 90 (21.0%) had a good outcome (MRS 0-3). Of 430 allocated avoid tube feeding 207 (48.1%) died, 137 (31.9%) were alive with poor outcome and 85 (19.8%) had a good outcome. Early tube feeding was associated with an absolute reduction in risk of death of 5.8% (95% CI -0.8 to 12.5; p = 0.09) and a reduction in death or poor outcome of 1.2% (95% CI -4.2 to 6.6; p = 0.7). In Trial 3, 321 patients were enrolled by 47 hospitals in 11 countries. Of 162 allocated PEG, 79 (48.8%) died, 65 (40.1%) were alive with poor outcome and 18 (11.1%) had good outcome. Of 159 allocated NG, 76 (47.8%) died, 53 (33.3%) were alive with poor outcome and 30 (18.9%) had good outcome. PEG was associated with an increase in absolute risk of death of 1.0% (95% CI -10.0 to 11.9; p = 0.9) and an increased risk of death or poor outcome of 7.8% (95% CI 0.0 to 15.5; p = 0.05). CONCLUSIONS: The results of Trial 1 would be compatible with oral supplementation being associated with a 1-2% absolute benefit or harm, but do not support routine supplementation of hospital diet for unselected stroke patients who are predominantly well nourished on admission. In Trial 2, the data suggest that a policy of early tube feeding may substantially reduce the risk of dying after stroke and it is very unlikely that the alternative policy of avoiding early tube feeding would significantly improve survival. Improved survival may be at the expense of increasing the proportion surviving with poor outcome. These data might usefully inform the difficult discussions about whether or not to feed a patient with a severe stroke. In Trial 3, the data suggest that in the first 2-3 weeks after acute stroke, better functional outcomes result from feeding via NG tube than PEG tube, although there was no major difference in survival. These data do not support a policy of early initiation of PEG feeding in dysphagic stroke patients. Future research might be focused on making NG tube feeding safer and more effective, also studies need to confirm the increased risk of gastrointestinal haemorrhage associated with tube feeding and, if confirmed, establish whether any interventions might reduce this risk. Future work might also aim to establish why worse functional outcomes occurred in PEG-fed patients because patients with prolonged dysphagia or intolerance of an NG tube are inevitably fed via a PEG tube.

Aged↗
PubMed2005

Functional outcome in young adults with spina bifida and hydrocephalus.

INTRODUCTION: Quality of life was studied in 31 adult survivors of spina bifida, each with Verbal or Performance IQ score over 70. METHODS: Instruments measured physical and occupational function, cognitive/psychological function, somatic sensation, and social interaction in the context of the ability to live independently. RESULTS: Domain group means except motor independence were in the average range (+/- 1 standard deviation). Variability within the group with respect to physical phenotype (high spinal lesions were associated with poorer motor independence) and medical history [a greater number of shunt revisions (> 4) were associated with poorer functional numeracy] was predictive of quality of life. Both spinal lesion level and number of shunt revisions influenced occupational status. DISCUSSION: There was a relation between everyday mathematics, reading skills, and quality of life. The consequences of the physical, medical, and cognitive effects of spina bifida extend into young adulthood and have an impact on quality of life.

Activities of Daily Living↗
PubMed2005

Saccades in children with spina bifida and Chiari type II malformation.

BACKGROUND: Saccades are essential for optimal visual function. Chiari type II malformation (CII) is a congenital anomaly of the cerebellum and brainstem, associated with spina bifida. OBJECTIVE: To investigate the effects of CII on saccades and correlate saccadic parameters with brain MRI measurements. METHODS: Saccades were recorded in 21 participants with CII, aged 8 to 19, using an infrared eye tracker. Thirty-nine typically developing children served as controls. Participants made saccades to horizontal and vertical target steps. Nineteen participants with CII had MRI. Regression analyses were used to investigate the effects of spinal lesion level, number of shunt revisions, presence of nystagmus, and midsagittal MRI measurements on saccades. RESULTS: Saccadic amplitude gains, asymptotic peak velocities, and latencies did not differ between the control and CII groups (p > 0.01). No significant differences were found between saccadic gains, asymptotic peak velocities or latencies, and spinal lesion level, number of shunt revisions, presence of nystagmus, or MRI measurements. CONCLUSIONS: Saccades were normal in most participants with Chiari II malformation (CII). Neural coding of saccades is robust and is typically not affected by the anatomic deformity of CII.

Adolescent↗
PubMed2005

Gluten-free diet survey: are Americans with coeliac disease consuming recommended amounts of fibre, iron, calcium and grain foods?

OBJECTIVE: This survey was conducted to assess nutrient intakes and food consumption patterns of adults with coeliac disease who adhere to a strict gluten-free diet. DESIGN: Three-day estimated self-reported food records were used to assess daily intakes of calories, percent daily calories from carbohydrates, dietary fibre, iron, calcium and grain food servings. SUBJECTS: Volunteers for this survey were recruited through notices placed in coeliac disease support group newsletters, as well as a national magazine for persons with coeliac disease. Forty-seven volunteers met all criteria for participation and returned useable food records. RESULTS: Group mean daily intake of nutrients by gender: Males (n = 8): 2882 calories; 55% carbohydrate; 24.3 g dietary fibre; 14.7 mg iron; 1288.8 mg calcium; 6.6 grain food servings. Females (n = 39): 1900 calories; 52% carbohydrate; 20.2 g dietary fibre; 11.0 mg iron; 884.7 mg calcium; 4.6 grain food servings. Recommended amounts of fibre, iron and calcium were consumed by 46, 44 and 31% of women and 88, 100 and 63% of men, respectively. CONCLUSIONS: Nutrition therapy for coeliac disease has centred around food allowed/not allowed on a gluten-free diet. Emphasis also should be placed on the nutritional quality of the gluten-free diet, particularly as it concerns the iron, calcium and fibre consumption of women. The use of the estimated food record as the dietary survey method may have resulted in the under-reporting of energy intake. Due to the small sample size and possible bias of survey participants, the findings of this survey may not be representative of the larger coeliac community.

Adult↗
PubMed2004

Red cell N5-methyltetrahydrofolate concentrations and C677T methylenetetrahydrofolate reductase genotype in patients with stroke.

AIMS: To investigate the relation between total red cell folate, red cell N(5)-methyltetrahydrofolate (N(5)MTHF) concentrations, and N(5)N(10)-methylenetetrahydrofolate reductase (MTHFR) genotypes in stroke. METHODS: The study comprised 120 consecutive patients presenting to hospital with acute stroke. Multivitamin supplement use was recorded. Serum and red cell folate were measured by microbiological assays using Lactobacillus casei and Enterococcus faecalis, and by the DPC-BioMediq Immulite 2000 analyser. Total plasma homocysteine (tHcy), serum cobalamin, and serum vitamin B(6) were measured and the C677T MTHFR genotype determined. RESULTS: There were no significant differences in blood tHcy or vitamin concentrations according to MTHFR genotype in the overall patient cohort. However, when patients taking vitamins were excluded, total red cell folate and red cell N(5)MTHF were significantly lower in patients with the TT genotype compared with CT or CC genotypes. In the overall cohort, irrespective of genotype, red cell folate was significantly lower when assayed microbiologically than with the Immulite assay. This discrepancy remained after exclusion of patients taking vitamins. CONCLUSION: Total red cell folate and red cell N(5)MTHF are significantly lower in stroke patients with the TT compared with the CT and TT MTHFR genotypes, particularly those not taking vitamin supplements. Microbiological assays that measure biologically active folates provide substantially lower estimates of folate than the Immulite assay. Because folate is a key determinant of blood homocysteine values, these findings may impact on the interpretation of the strength and independence of the association between raised blood concentrations of homocysteine and atherothrombosis risk reported in most epidemiological studies.

Acute Disease↗
PubMed2004

Predicting functional outcome in acute stroke: comparison of a simple six variable model with other predictive systems and informal clinical prediction.

BACKGROUND: Statistical models that predict functional outcome after stroke using six simple variables (SSV) have recently been developed and validated. OBJECTIVE: To compare the accuracy of these models with other simple ways of predicting outcome soon after stroke. METHODS: The SSV model for being alive and independent (modified Rankin score < or =2) six months or one year after stroke was compared with predictions based on a model that included only age and Oxford community stroke project classification, with predictions based on conscious level and urinary continence, and with informal clinical predictions made by clinicians interested in stroke. Predictions were compared in an independent hospital based cohort of stroke patients using receiver operator characteristic (ROC) curves. RESULTS: The SSV model at six months had a significantly greater area under the curve (0.84) than the model with only age and stroke classification (0.75). Predictions based on conscious level and urinary continence were no better than those of the SSV model and were unable to predict subjects with a high probability of good outcome. The sensitivity and specificity for informal clinical predictions at one year lay on or below the SSV model curve, implying that the SSV model was at least as good as clinical predictions. CONCLUSIONS: The SSV models performed as well as or better than other simple predictive systems. These models will be useful in epidemiological studies but should not be used to guide clinical management until their impact on patient care and outcome has been evaluated.

Activities of Daily Living↗
PubMed2004

Improvements in carotid endarterectomy in Scotland: results of a national prospective survey.

BACKGROUND AND AIMS: The effectiveness of carotid endarterectomy (CEA) depends upon selection of patients with a high absolute risk of stroke, avoidance of delays from intial presentation to surgery and provsion of surgery with a low perioperative risk of stroke. We evaluated these aspects of practice in Scottish hospitals and, by encouraging adherence to national (SIGN) guidelines, attempted to improve the effectiveness of CEA. METHODS: Prospective independent survey of patient selection, pre-operative delays and surgical performance for all CEAs performed in Scottish National Health Service hospitals over two 13 month periods from September 1997 and February 1999 respectively. RESULTS: Thirteen hospitals performed 485 CEAs in the first period and 392 in the second, equating to an overall annual rate of 79 per million population. During both periods at least 95% of patients reported symptoms of carotid terittory ischaemia, but the proportion with stenoses greater than >70% rose from 89% to 97% (p<0.0001). The delays between referral, surgical consultation and subsequent surgery fell significantly but remained unacceptably long. The proportion seen by the surgeon within two weeks of referral rose from 36% to 43% (p=0.05) and the proportion operated on within one month thereafter rose from 35% to 49% (p<.0001). The perioperative combined major stroke and death rate was 3% in both periods. CONCLUSION: We demonstrated significant changes in practice, in line with national guidelines, which would be expected to improve the effectiveness of our national programme of CEA. There is further scope for improving performance, particularly in relation to pre-operative delays.

Aged↗
PubMed2004

N-ViroTech--a novel process for the treatment of nutrient limited wastewaters.

As pulp and paper wastewaters are mostly deficient in nitrogen and phosphorus, historical practice has dictated that they cannot be effectively treated using microbiological processes without the addition of supplementary nutrients, such as urea and phosphoric acid. Supplementation is a difficult step to manage efficiently, requiring extensive post-treatment monitoring and some degree of overdosing to ensure sufficient nutrient availability under all conditions. As a result, treated wastewaters usually contain excess amounts of both nutrients, leading to potential impacts on the receiving waters such as eutrophication. N-ViroTech is a highly effective alternative treatment technology which overcomes this nutrient deficiency/excess paradox. The process relies on communities of nitrogen-fixing bacteria, which are able to directly fix nitrogen from the atmosphere, thus satisfying their cellular nitrogen requirements. The process relies on manipulation of growth conditions within the biological system to maintain a nitrogen-fixing population whilst achieving target wastewater treatment performance. The technology has significant advantages over conventional activated sludge operation, including: Improved environmental performance. Nutrient loadings in the final treated effluent for selected nitrogen and phosphorus species (particularly ammonium and orthophosphate) may be reduced by over 90% compared to conventional systems; Elimination of nitrogen supplementation, and minimisation of phosphorus supplementation, thus achieving significant chemical savings and resulting in between 25% and 35% savings in operational costs for a typical system; Self-regulation of nutrient requirements, as the bacteria only use as much nitrogen as they require, allowing for substantially less operator intervention and monitoring. This paper will summarise critical performance outcomes of the N-ViroTech process utilising results from laboratory-, pilot-scale and recent alpha-adopter, full-scale trials.

Bacteria↗
PubMed2001

Analysis of SIV-specific CTL in the rhesus macaque model of AIDS: the use of simian fibroblasts as an alternative source of target cells for chromium release assays.

The simian immunodeficiency virus (SIV) model of AIDS is widely used for the development of human immunodeficiency virus (HIV) vaccine strategies, particularly for the analysis of correlates of protective immunity. As it is not always possible to establish autologous B-lymphoblastoid cell lines (B-LCL) for use as targets in the analysis of cytotoxic T cell (CTL) activity, we have compared B-LCL with primary simian skin cells. Using a well-defined SIV gag-encoded CTL epitope restricted by Mamu A*01 major histocompatibility complex (MHC) class I, we have shown that peripheral blood mononuclear cells (PBMC) from vaccinated and infected macaques can kill MHC class I-matched skin fibroblasts presenting the cognate epitope but that skin fibroblasts are a less sensitive target than B-LCL for the detection of CTL.

Acquired Immunodeficiency Syndrome↗
PubMed2001

Mucosal exposure to subinfectious doses of SIV primes gut-associated antibody-secreting cells and T cells: lack of enhancement by nonneutralizing antibody.

It has been suggested that the presence of immunoglobulin and complement receptors on rectal epithelium may facilitate the entry of HIV complexed to nonneutralizing antibody. We tested this hypothesis using simian immunodeficiency virus (SIV) infection of rhesus macaques. First, in a pilot study, a nonneutralizing IgG fraction of macaque anti-SIV gp120 was shown to enhance the immunogenicity of SIV envelope following rectal immunization. The same antibody was then mixed with a subinfectious dose of SIV and the occurrence of rectal infection was compared with virus alone. Animals were not infected overtly and were rechallenged with a 10-fold higher dose of virus with and without addition of antibody. There was no evidence of antibody-mediated infection, since equal numbers of macaques became infected, regardless of the presence of antibody. In addition, the application of immune complexes did not alter significantly the subsequent virus load or the immune responses generated. In seronegative animals, in which virus and proviral DNA were undetectable in PBMC and tissues, SIV-specific T-cell responses and antibody-secreting cells were found in systemic and gut-associated sites. Our results show that nonneutralizing antibody neither facilitated nor enhanced rectal infection with SIV, in the small number of animals used, despite the consistent trend for this antibody to enhance antibody responses to gp120 following rectal immunization with immune-complexed antigen. However, mucosal exposure to subinfectious doses of virus primed both systemic and local immunity, regardless of addition of nonneutralizing antibody.

Animals↗
PubMed2001

Rhythm and melody in children and adolescents after left or right temporal lobectomy.

Rhythm (a pattern of onset times and duration of sounds) and melody (a pattern of sound pitches) were studied in 22 children and adolescents several years after temporal lobectomy for intractable epilepsy. Left and right lobectomy groups discriminated rhythms equally well, but the right lobectomy group was poorer at discriminating melodies. Children and adolescents with right lobectomy, but not those with left temporal lobectomy, had higher melody scores with increasing age. Rhythm but not melody was related to memory for the right lobectomy group. In neither group was melody related to age at onset of non-febrile seizures, time from surgery to music tests, or the linear amount of temporal lobe resection. Pitch and melodic contour show different patterns of lateralization after temporal lobectomy in childhood or adolescence.

Adolescent↗