Search PubMed⌕ Search

Biomedical subjects

M Dennis

Publications and source records attributed to M Dennis.

At least 73 records · Page 4Linked to original sources

Discourse after early-onset hydrocephalus: core deficits in children of average intelligence.

A review of our studies of oral and written language in children with early-onset hydrocephalus suggests that hydrocephalus is associated with specific deficits in discourse as opposed to generalized linguistic deficit. It is proposed that the language skills that are impaired in hydrocephalus are those that require context to derive meaning, while those that are intact may function relatively independent of particular discourse contexts. This hypothesis was tested in two discourse studies comparing children with hydrocephalus of average verbal IQ to age-matched controls. Study 1 investigated narrative economy, syntactic complexity, and semantic content in the retellings of familiar and less familiar fairy tales. Despite producing quantities of story content similar to controls and using syntactic economy similar to controls, the hydrocephalus group produced less of the core semantic content of both familiar and less familiar tales. Study 2 investigated inferencing and figurative language understanding in a narrative comprehension task. Even when prior knowledge was controlled, the hydrocephalus group had difficulty making inferences and recalling factual information from the story. In contrast to their ability to understand idiomatic figurative expressions, the hydrocephalus group had difficulty interpreting novel figurative expressions. The results are compatible with the hypothesis that the core discourse deficits characteristic of children with hydrocephalus are concerned with computing meaning from context. Putative processing features underlying the proposed core discourse deficit are discussed.

Adolescent↗

Assessment of patients with memory problems using a nurse-administered instrument to detect early dementia and dementia subtypes.

BACKGROUND: With the development of pharmacological treatments for Alzheimer's disease there will be an increase in the numbers of patients requiring assessment from specialist services. Could the role of the specialist clinician be supported by other health professionals screening those who might benefit from treatment? METHOD: Sixty-four consecutive referrals to the Leicester University Memory Clinic were assessed at home by a community psychiatric nurse using a semi-structured interview. The nurse then reported her findings to a psychiatrist and a diagnosis was agreed. This diagnosis was then compared to the Memory Clinic diagnosis and a standardized (ICD-10) diagnosis recorded by another psychiatrist examining the clinic records. RESULTS: The nurse assessment procedure performed well in detecting dementia, with a kappa statistic (k) of 0.75 when compared to the standardized and Memory Clinic diagnoses. There was, however, only moderate concordance between the ICD-10 diagnosis and nurse (k = 0.46) and the Memory Clinic and nurse (k = 0.60) for Alzheimer's disease. The relatively low k value for Alzheimer's disease was principally a result of difficult in differentiating vascular dementia. CONCLUSIONS: A single supervised community psychiatric nurse, using a structured assessment instrument, can adequately detect early dementia in a sample of patients referred with memory problems. Subtypes of dementia are not, however, accurately differentiated.

Adult↗

Expression and recovery of functional G-protein-coupled receptors using baculovirus expression systems.

Baculovirus expression systems have been used for more than ten years as the tool of choice to over-express G-protein-coupled receptors. Although this expression system has also been used to study the signaling mechanisms of the receptors at the cellular level, it was found to be a most useful method to produce large quantities of receptors for biochemical and biophysical studies. Methods that allow easy and selective recovery of properly folded and mature receptors in viral particles open new perspectives for such applications.

Animals↗

Qualitative comparison of the reliability of health status assessments with the EuroQol and SF-36 questionnaires after stroke. United Kingdom Collaborators in the International Stroke Trial.

BACKGROUND AND PURPOSE: The reliability of the EuroQol and SF-36 questionnaires after stroke is not known. We therefore aimed to assess and compare the test-retest reliability of both instruments in a group of stroke patients. METHODS: A total of 2253 patients with stroke entered by United Kingdom hospitals in the International Stroke Trial were randomized to follow up with either the EuroQol or the SF-36 instruments. For both instruments, we randomly selected one third of respondents and asked them to complete another, identical questionnaire. We assessed test-retest reliability using agreement statistics: unweighted kappa statistics for the categorical domains of the EuroQol and intraclass correlation coefficients for the EuroQol visual analog scale, utility scores, and SF-36. RESULTS: For the five categorical domains of the EuroQol, reproducibility was generally good (kappa ranged from 0.63 to 0.80). The reproducibility of the domains of the SF-36 was qualitatively similar for all the domains except mental health (intraclass correlation coefficient=.28). However, the 95% confidence intervals for the difference in scores between test and retest were substantial. For both instruments, reproducibility was better when the patient completed the questionnaires than when a proxy did. CONCLUSIONS: Both the EuroQol and SF-36 have acceptable and qualitatively similar test-retest reliability. Therefore, either instrument might function effectively as a discriminatory measure for assessing health-related quality-of-life outcomes in groups of patients after stroke. However, our data do not support the use of either instrument for serial assessments in individual patients unless very large differences over time are expected.

Activities of Daily Living↗

Detecting psychiatric morbidity after stroke: comparison of the GHQ and the HAD Scale.

BACKGROUND AND PURPOSE: Mood disorders are common after stroke and may impede physical, functional, and cognitive recovery, making early identification and treatment of potential importance. We aimed to compare the accuracy of the General Health Questionnaire (GHQ-30) and the Hospital Anxiety and Depression (HAD) Scale in detecting psychiatric morbidity after stroke and to determine the most suitable cutoff points for different purposes. METHODS: One hundred five hospital-referred stroke patients completed both the GHQ-30 and HAD Scale 6 months after onset before a blinded psychiatric assessment in which the Schedule for Affective Disorders and Schizophrenia with some supplementary questions was used to determine a DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) diagnosis. Measures were compared in terms of sensitivity, specificity, and receiver operating characteristic curves. RESULTS: No significant differences were found between the GHQ-30 and the HAD Scale in identifying those patients with any DSM-IV diagnosis (P=0.95), grouped depression (P=0.56), or anxiety (P=0.25) disorders. The previously recommended cutoff points for identifying "cases" for the GHQ (4/5) and for the HAD Scale (8/9 and 11/12) were found to be suboptimal in this population. CONCLUSIONS: The GHQ-30 and HAD scale exhibited similar levels of sensitivity and specificity. Data are presented, taking into account the "cost" of false-positives and negatives, to allow a choice of cutoff points suitable for differing situations.

Adolescent↗

A quantitative study of the emotional outcome of people caring for stroke survivors.

BACKGROUND AND PURPOSE: Although the physical and, to a lesser extent, emotional outcome of stroke survivors has been well documented, there are far fewer data relating to the outcomes of those who care for them. We aimed to describe the outcome of those caring for stroke patients and to identify both patient and caregiver factors that are associated with poor caregiver outcomes. METHODS: As part of a randomized trial to evaluate a stroke family care worker, we identified 417 patients (67% of all referrals to our institution). We followed up 376 survivors of whom 246 identified a caregiver at a 6-month follow-up interview. The patients and caregivers were asked to complete 2 measures of emotional distress ( 30-item General Health Questionnaire [GHQ-30] and Hospital Anxiety and Depression [HAD] Scale). A regression analysis was used to identify factors that were independently associated with poor caregiver outcomes. RESULTS: Fifty-five percent of responding caregivers scored more than 4 on the GHQ-30, indicating that emotional distress is common in this group. Caregivers were more likely to be depressed if the patients were severely dependent (P<0.01) or emotionally distressed themselves (P<0.01). Female caregivers reported more anxiety (median HAD=8) than male caregivers (median HAD=5; P<0.01) but caregivers' levels of anxiety were not so clearly related to the patients' degree of physical disability as their levels of depression. Caregivers suffered more emotional distress if the patients had been dependent before their strokes. CONCLUSIONS: These data may help to identify those caregivers at greatest risk of poor emotional outcomes and thus help in the planning of trials and delivery of interventions aimed at preventing or treating distress among caregivers.

Activities of Daily Living↗

Protective mucosal immunity elicited by targeted lymph node immunization with a subunit SIV envelope and core vaccine in macaques.

Prevention of sexually transmitted HIV infection was first investigated in non-human primates by mucosal immunization via the rectal, vaginal or male urethral route. This was compared with subcutaneous targeted iliac lymph node (TILN) and systemic intramuscular immunization in non-human primates. TILN immunization elicited the most consistent mucosal sIgA and IgG antibody response in the rectum, vagina, urine and seminal fluid, as well as in blood. Both mucosal and TILN immunization induced a specific CD4+ T cell proliferative response in the iliac lymph nodes which drain these mucosal surfaces, and in the splenic and circulating T cells. In the next experiment macaques were immunized by the TILN route with SIV gp120 and p27 in alum. Rectal mucosal challenge with SIVmac 32H J5 molecular clone (or cell-free virus) induced total protection in four out of seven macaques, compared with infection in 13 of 14 unimmunized macaques or immunized by other routes (p = 0.025). The remaining three macaques immunized by the TILN route showed either decrease in viral load (> 90%) or transient viraemia, indicating that all seven TILN immunized macaques showed total or partial protection of rectal transmission by SIV (p = 0.001). Protection was associated with significant increase in the iliac lymph nodes IgA antibody secreting cells to p27 (p < 0.02), CD8-suppressor factor inhibiting replication of SIV in CD4+ T cells (p < 0.01) and the chemokines RANTES and MIP-1 beta (p < 0.01). We suggest that administration of gp120 and p27 by the TILN route may elicit protective B and T cell immunity which can significantly prevent rectal transmission of SIV or HIV.

Animals↗

Epileptic seizures after a first stroke: the Oxfordshire Community Stroke Project.

OBJECTIVE: To describe the immediate and long term risk of epileptic seizures after a first ever stroke. DESIGN: Cohort study following up stroke survivors for 2 to 6.5 years; comparison with age specific incidence rates of epileptic seizures in the general population. SETTING: Community based stroke register. SUBJECTS: 675 patients with a first stroke, followed up for a minimum of 2 years. MAIN OUTCOME MEASURES: Occurrence of single and recurrent seizures. RESULTS: 52 patients had one or more post stroke seizures; in 25 the seizures were recurrent. The 5 year actuarial risk of a post stroke seizure in survivors (excluding 19 patients with a history of epilepsy and 3 patients in whom the seizure occurred shortly before death from another cause) was 11.5% (95% confidence interval 4.8% to 18.2%). The relative risk of seizures, in comparison with the general population, was estimated at 35.2 in the first year after stroke and 19.0 in year 2. The risk of seizures was increased in survivors of subarachnoid and intracerebral haemorrhage (hazard ratio for intracranial haemorrhage v cerebral infarction 10.2 (3.7 to 27.9)). The risk of seizures after ischaemic stroke was substantial only in patients presenting with severe strokes due to total anterior circulation infarction. Only 9 of 295 patients (3%) independent one month after stroke suffered a seizure between 1 month and 5 years (actuarial risk 4.2% (0.1% to 8.3%)). CONCLUSION: Stroke patients have about an 11.5% risk of single or recurrent seizures in the first 5 years after a stroke. Patients with more severe strokes or haemorrhagic strokes are at higher risk.

Adolescent↗

Anti-major histocompatibility complex antibody responses to simian B cells do not protect macaques against SIVmac infection.

Macaques have been protected against infection with human cell-grown SIVmac by immunization with antigens encoded by the human major histocompatibility complex (MHC). Here, we investigated the efficacy of alloimmunization with simian B cells expressing high levels of MHC class I and class II molecules to confer protection against systemic challenge with simian-grown SIVmac. Eight rhesus macaques were vaccinated with glutaraldehyde-fixed and beta-propiolactone-inactivated herpesvirus papio-transformed B cells. Four of the macaques received 5 doses, the others 10. Animals were challenged with rhesus macaque spleen-derived cell-free SIVmac. Allogeneic B cells elicited antibody responses to rhesus MHC class I and II but failed to protect animals against infection. Anti-MHC class I antibodies were restricted in specificity and failed to recognize MHC class I from some B lymphoblastoid cell lines (B-LCLs) including a B-LCL from the animal in whose cells the challenge virus was grown. Vaccinated animals responded to self-MHC class I antigens but not to self-MHC class II antigens from peripheral blood mononuclear cells (PBMCs). Animals that underwent the shorter immunization regimen had transiently enhanced PBMC-associated virus loads after challenge, whereas the average virus-infected cell load was reduced in animals that underwent the more extensive immunization. These results suggest that antibody responses to allogeneic MHC molecules do not protect against infection with immunodeficiency lentiviruses.

Adoptive Transfer↗

Evaluation of a stroke family care worker: results of a randomised controlled trial.

OBJECTIVE: To examine the effect of contact with a stroke family care worker on the physical, social, and psychological status of stroke patients and their carers. DESIGN: Randomised controlled trial with broad entry criteria and blinded outcome assessment six months after randomisation. SETTING: A well organised stroke service in an Edinburgh teaching hospital. SUBJECTS: 417 patients with an acute stroke in the previous 30 days randomly allocated to be contacted by a stroke family care worker (210) or to receive standard care (207). The patients represented 67% of all stroke patients assessed at the hospital during the study period. MAIN OUTCOME MEASURES: Patient completed Barthel index, Frenchay activities index, general health questionnaire, hospital anxiety and depression scale, social adjustment scale, mental adjustment to stroke scale, and patient satisfaction questionnaire; carer completed Frenchay activities index, general health questionnaire, hospital anxiety and depression scale, social adjustment scale, caregiving bassles scale, and carer satisfaction questionnaire. RESULTS: The groups were balanced for all important baseline variables. There were no significant differences in physical outcomes in patients or carers, though patients in the treatment group were possibly more helpless less well adjusted socially, and more depressed, whereas carers in the treatment group were possibly less hassled and anxious. However, both patients and carers in the group contacted by the stroke family care worker expressed significantly greater satisfaction with certain aspects of their care, in particular those related to communication and support. CONCLUSIONS: The introduction of a stroke family care worker improved patients' and their carers' satisfaction with services and may have had some effect on psychological and social outcomes but did not improve measures of patients' physical wellbeing.

Activities of Daily Living↗

New non-peptide endothelin-A receptor antagonists: synthesis, biological properties, and structure-activity relationships of 5-(dimethylamino)-N-pyridyl-,-N-pyrimidinyl-,-N-pyridazinyl-, and -N-pyrazinyl-1-naphthalenesulfonamides.

Use of automated synthesis led to the discovery of several 6-membered nitrogen heterocycles as replacements for the N-isoxazolyl substituent present in the 1-naphthalenesulfonamides endothelin-A (ETA) antagonist 5-(dimethylamino)-N-(3,4-dimethyl-5-isoxazolyl)-1-naphthalenesu lfo namides (BMS 182874). In each of these heterocycles, a small substituent such as halogen para to the position of attachment to the sulfonamide nitrogen atom was found to be advantageous for ETA receptor affinity. Of these heterocycles, 2-pyrazines offered the greatest scope for improving receptor affinity. Optimization of the substituents at the 3- and 5-positions in the pyrazine ring led to potent, ETA-selective compounds such as 5-(dimethylamino)-N-(5-chloro-3-methoxy-2-pyrazinyl)-1- naphthalenesulfonamides (7m, ETA pIC50 8.1). When dosed orally at 10 mg/kg to conscious, normotensive rats infused with big ET-1, compounds such as 7m showed significant inhibition of the pressor response with a duration of effect lasting for the 5-h course of the experiment.

Animals↗

An examination of the accident and emergency management of deliberate self harm.

OBJECTIVE: To examine the adequacy of assessment and management of deliberate self harm (DSH) undertaken by accident and emergency (A&E) medical staff. METHODS: The records for attendances to the Leicester Royal Infirmary A&E department with a diagnosis of "self inflicted" injury for the 12 month period April 1994 to March 1995 were scrutinised. If the episode was identified as DSH, then assessment and management were examined, using an instrument based on the Royal College of Psychiatrists' standards of service for the general hospital management of adult DSH. RESULTS: There were 934 episodes of DSH involving 854 patients. The mean age was 32 (SD 14.2), with an even sex distribution. Overdose was by far the most common method of DSH (91.5%). Information concerning suicide intent was documented in 70% of cases, and psychiatric history in 67%. Less information was recorded for medical history (50%), mental state (51%), recent stress (55%), or previous DSH (47%), and only 23% had an assessment of risk of further DSH. Very little was recorded concerning alcohol or substance misuse. In 291 cases (31%), the patient was discharged directly home by A&E medical staff, and 50 of these were referred for psychiatric outpatient follow up; 210 (23%) were referred for specialist assessment in the department and 423 (45.5%) were admitted to medical/surgical wards. The frequency with which information was recorded varied significantly between outcome groups. At night A&E staff were far more likely to discharge a patient home themselves than refer for specialist assessment (P << 0.001). CONCLUSIONS: With over half the sample not admitted, the responsibility for the initial risk assessment lies with A&E medical staff. The study reveals a need for improved planning and delivery of services.

Adolescent↗

Effect of pranlukast, an oral leukotriene receptor antagonist, on leukotriene D4 (LTD4) challenge in normal volunteers.

BACKGROUND: There is increasing evidence to show that leukotrienes are important mediators in asthma. Leukotriene receptor antagonists protect against antigen and exercise challenges in patients with chronic asthma. A study was undertaken to investigate the activity of the leukotriene receptor antagonist pranlukast (SB 205312, ONO-1078) in blocking bronchoconstriction induced by leukotriene D4 (LTD4) inhalation. The selectivity of pranlukast was evaluated using histamine challenge. METHODS: Pranlukast, 450 mg twice daily, was given to eight healthy non-smoking men for five days in a randomised, double blind, placebo controlled, crossover study. The specific airways conductance (sGaw) was measured before and after bronchial provocation with inhaled LTD4 at 3.5 hours after the first dose and at 3.5 and 9.5 hours after the last dose of pranlukast on the morning of day 5. The concentration of LTD4 required to produce a fall in sGaw of 35% (PC35) was calculated. Subjects also underwent a histamine challenge 3.5 hours after a single dose of pranlukast, 450 mg, or placebo. RESULTS: A single dose of pranlukast produced a 10.6 fold increase in PC35sGaw (95% confidence interval (CI) 4.4 to 25.5; p < 0.001) for LTD4 at 3.5 hours after dosing compared with placebo. Three and a half hours after the morning dose of pranlukast on day 5 the PC35sGaw for LTD4 was increased 25.9 fold (95% CI 10.8 to 62.2; p < 0.001) and was still increased sevenfold (95% CI 2.9 to 16.7; p < 0.001) relative to placebo 9.5 hours after administration of the morning dose. No significant differences were noted for the PC35sGaw to histamine for pranlukast compared with placebo. CONCLUSIONS: This study shows that pranlukast is a potent and selective LTD4 receptor antagonist in humans which blocks LTD4 challenge after initial and repeated administration when given twice daily for five days.

Administration, Inhalation↗

Is the EuroQol a valid measure of health-related quality of life after stroke?

BACKGROUND AND PURPOSE: The EuroQol measures aspects of quality of life that are highly relevant to stroke patients. It is short and simple and many stroke patients can complete the form without help. However, its validity has not been adequately assessed after stroke. We therefore assessed its concurrent and discriminant validity in a group of prospectively studied stroke survivors. METHODS: We assessed the validity of the EuroQol in a series of 152 patients with stroke who were all visited by a study nurse. The nurse gave the patients the EuroQol, the Frenchay Activities Index, a visual analogue pain scale, and the Hospital Anxiety and Depression Scale in the form of questionnaires to be self-completed where possible. The nurse interviewed the patient directly to assess disability using the Office of Population Censuses and Surveys Disability scale and Barthel Index. RESULTS: The nurse assessed 152 patients; of these 92 were able to complete the EuroQol without help, the remaining 60 could only be assessed by interview. The EuroQol had reasonable concurrent validity; median scores on the relevant standard instruments varied significantly (and in the appropriate direction) for groups defined by their response to the relevant EuroQol domain. The EuroQol had reasonable discriminant validity since the responses enabled separation between patients with differing stroke syndromes and stroke severities. Accuracy for predicting outcome after stroke was good for both self-completed and interview-completed questionnaires. CONCLUSIONS: The EuroQol appears to have acceptable concurrent and discriminant validity for the measurement of health-related quality of life after stroke. It may be administered by either a questionnaire for self-completion in patients with mild to moderate stroke or by interview in patients with significant motor deficits.

Aged↗

Are proxy assessments of health status after stroke with the EuroQol questionnaire feasible, accurate, and unbiased?

BACKGROUND AND PURPOSE: It is often difficult to determine the health-related quality of life (HRQoL) of stroke patients because physical and cognitive problems limit their ability to complete complex questionnaires. A proxy, such as a family member or caregiver, may be able to give an estimate of the patients' health status. We therefore examined the agreement between the HRQoL as assessed by a series of patients and that assessed by their proxies. METHODS: We studied the validity of the EuroQol in a series of 152 patients from our prospective registry of patients with first (or recurrent) stroke. We asked patients to ensure that a friend or relative (a proxy) who knew them well was available at the time of the interview. We asked each proxy to complete a EuroQol questionnaire independently on behalf of the patient. RESULTS: Proxies completed forms for 130 patients (86%). Agreement between responses from the patients and those from their proxies was better for patients who were able to self-complete the EuroQol than for patients who required the EuroQol to be administered by interview. For both groups, agreement was best for the self-care domain and worst for the domain that assessed psychological outcome. For the more severely affected patients, agreement was only fair for the pain and social functioning domains and no better than chance alone for the psychological functioning domain (kappa = 0.05, 95% confidence interval, 0 to 0.43). Patients tended to rate their own health status as better than their proxies did (P < .05). CONCLUSIONS: We found moderate agreement between responses from patients and those from their proxies for the more directly observable domains of the EuroQol. Proxy agreement was less good for the more subjective domains. In health surveys, allowing responses by a proxy increases response rate. However, the disadvantages inherent in the use of proxy responses must be considered carefully. In general, some domains of HRQoL information obtained from a proxy may be sufficiently valid and unbiased to be useable in most types of trials and surveys.

Caregivers↗