Search PubMed⌕ Search

Biomedical subjects

M Dennis

Publications and source records attributed to M Dennis.

At least 145 records · Page 8Linked to original sources
PubMed1990

Expression and pharmacological characterization of the human M1 muscarinic receptor in Saccharomyces cerevisiae.

The yeast S. cerevisiae has been examined as a heterologous host for the expression of mammalian neurotransmitter receptors which couple to guanine nucleotide regulatory (G) proteins. A cloned gene encoding the M1 subtype of human muscarinic receptor (HM1) was transformed into S. cerevisiae on a high copy plasmid under the control of the promoter for the yeast alcohol dehydrogenase (ADH) gene. Northern blotting demonstrated the presence of HM1 transcripts in transformants, and crude membranes prepared from these cells showed saturable binding of the muscarinic antagonist [3H]N-methyl scopolamine with a Kd of 179 pM and Bmax of 20 fmol/mg protein. Competition binding studies revealed pharmacological properties for these sites which were comparable to those reported for the M1 site in mammalian tissues. Yeast expressing HM1 did not exhibit high affinity agonist binding or cell-cycle arrest in the presence of muscarinic agonists, indicating that the mammalian receptor did not couple to the endogenous yeast G protein.

Base Sequence↗
PubMed1990

Computed tomography in patients with transient ischaemic attacks: when is a transient ischaemic attack not a transient ischaemic attack but a stroke?

In a prospective community-based study, 184 patients with transient ischaemic attacks (TIAs) were identified from a study population of about 105,000 between 1981 and 1986. Computed tomography (CT) was attempted in all those with cerebral ischaemic attacks (n = 152, 83%); patients with amaurosis fugax only (n = 32, 27%) were not scanned routinely. Scans were obtained in 120 (79%) of those with cerebral attacks and 12 (38%) of those with amaurosis fugax. The scans were reported by a neuroradiologist who was blinded to the patients' clinical features. Of 120 (27%:95% confidence interval 19-35) scans in patients with cerebral attacks, 32 showed a focal area of hypodensity or cortical loss, but in only 14 (12%:95% confidence interval 6-18) was this in an area of the brain appropriate to the patients' symptoms. There were no significant differences in the clinical features, the duration of attacks or the prognosis (i.e., risk of death, stroke or myocardial infarction) of patients with and without ischaemic lesions on CT. It is concluded that patients with clinically definite TIAs who have a presumed ischaemic and appropriately sited lesion on CT should not be re-classified as having had a stroke.

Aged↗
PubMed1990

Knowing the meaning, getting the point, bridging the gap, and carrying the message: aspects of discourse following closed head injury in childhood and adolescence.

Pragmatic communication or discourse was studied in 33 children and adolescents following closed head injury. Three-quarters of the sample was impaired on at least one of four discourse tests (knowing the alternate meanings of ambiguous words in context; getting the point of figurative or metaphoric expressions; bridging the inferential gaps between events in stereotyped social situations; and producing speech acts that express the apparent intentions of others). Resolution of ambiguity was correlated with word fluency and verbal domain knowledge, but not with object naming; understanding of metaphor was correlated with verbal domain knowledge, but not with literal sentence comprehension or with the formation of analogies; making inferences was correlated with working memory capacity but not with social knowledge; and producing speech acts was not correlated either with sentence construction or with social knowledge. These associations and dissociations reveal some of the correlates of impaired discourse processing after closed head injury in childhood and adolescence, as well as bearing on theoretical questions concerning the nature of normally developing discourse processes.

Adolescent↗
PubMed1990

The relationship between intellectual impairment and mood disorder in the first year after stroke.

In a community-based study of patients with a first-ever stroke, intellectual impairment (as defined by scores on a common screening test for dementia, the Mini-Mental State Examination) was found in 26% at 1 month post-stroke, and in 21% at 6 and 12 month follow-up. Low scores on the screening test were associated with greater age, physical disability before the stroke, larger stroke lesion volumes as measured on CT scan, and non-stroke changes such as atrophy and white matter low attenuation on the CT scan. There was a negative correlation between scores on the Mini-Mental State Examination and symptom levels on two measures of mood disorder. However, there was no evidence of a specific relationship between major depression and low scores on the Mini-Mental State. We examined various aspects of the relationship between mood symptoms and low scores on the Mini-Mental State, but found no evidence to support the suggestion that this relationship represented an example of depressive pseudodementia. We discuss the significance of our findings for clinical psychiatry and neuropsychology.

Adolescent↗
PubMed1990

Mood disorders after stroke and their relation to lesion location. A CT scan study.

In a community-based study of stroke survivors, we identified 73 consecutive patients with a stroke, the first ever in a lifetime, who had a CT scan which showed a neurologically appropriate single stroke lesion, and who did not have a psychiatric disorder in the year preceding the stroke. A detailed follow-up study of these patients using standardized psychiatric assessments failed to confirm a number of recent claims about poststroke depressive disorders. We found no evidence that left-sided lesions were associated with more severe or persistent depressive symptoms, or that right-sided lesions were associated with hypomania. The DSM III syndrome of major depression was much less common than has previously been reported, and was not specifically associated with lesions placed anteriorly in the left hemisphere. There was a weak correlation between mood symptom scores and the proximity of the stroke lesion to the frontal pole of the hemisphere, but no evidence of a difference between right and left hemisphere strokes in the nature of the relationship between lesion distribution and mood symptoms. We suggest that previous studies have different findings because of differences in the conventions applied to the definition and measurement of psychiatric disorders after stroke, and because other studies have concentrated on selected inpatient populations.

Adolescent↗
PubMed1990

A prospective study of acute cerebrovascular disease in the community: the Oxfordshire Community Stroke Project--1981-86. 2. Incidence, case fatality rates and overall outcome at one year of cerebral infarction, primary intracerebral and subarachnoid haemorrhage.

The age and sex specific incidence rates for cerebral infarction, primary intracerebral haemorrhage and subarachnoid haemorrhage in a population of approximately 105,000 are presented. Over four years 675 patients with a first-ever stroke were registered with the Oxfordshire Community Stroke Project. The pathological diagnosis was confirmed by computerised tomography (CT) scan, necropsy or lumbar puncture (cases of subarachnoid haemorrhage only) in 78% of cases and a further 17% were diagnosed according to the Guy's Hospital Stroke Diagnostic Score. The proportion of all first-ever strokes by pathological type was: cerebral infarction 81% (95% confidence interval 78-84), primary intracerebral haemorrhage 10% (8-12), subarachnoid haemorrhage 5% (3-7) and uncertain type 5% (3-7). These proportions are similar to other community-based studies. The overall 30 day case fatality rate was 19% (16-22), that for cerebral infarction being 10% (7-13), primary intracerebral haemorrhage 50% (38-62) and subarachnoid haemorrhage 46% (29-63). One year post stroke 23% (19-27) with cerebral infarction were dead and 65% (60-70) of survivors were functionally independent. The figures for primary intracerebral haemorrhage were 62% (43-81) dead and 68% (50-86) of survivors functionally independent and for subarachnoid haemorrhage were 48% (24-72) dead and 76% (56-96) of survivors functionally independent. There are important differences between these rates and those from other sources possibly due to more complete case ascertainment in our study. Nevertheless, the generally more optimistic early prognosis in our study, particularly for cases of cerebral infarction, has important implications for the planning of clinical trials and for the expected impact that any treatment might have on the general population.

Adolescent↗
PubMed1990

The frequency, causes and timing of death within 30 days of a first stroke: the Oxfordshire Community Stroke Project.

In a prospective, community-based study of 675 consecutive patients with a first-ever stroke, of whom over 90% had computed tomography (CT) and/or necropsy examinations, 129 deaths occurred within 30 days of the onset of symptoms, a case fatality rate (CFR) of 19%. The 30 day CFR for patients with cerebral infarction was 10% (57 of 545, for primary intracerebral haemorrhage 52% (34 of 66), for subarachnoid haemorrhage 45% (15 of 33) and for those of uncertain pathological type 74% (23 of 31). The CFR for patients who had been functionally dependent pre-stroke was 33% compared with 17% for those who had been independent pre-stroke. The age-adjusted relative risk of death for patients who had been functionally dependent pre-stroke was not significantly greater (1.8, 95% confidence interval 0 to 4.3). There was a significant trend for CFR to increase with age (Chi square for trend = 4.0, p less than 0.05). This relationship was found in those patients who had been functionally independent prestroke (Chi square for trend = 7.9, p less than 0.005) but not in those who had been dependent pre-stroke (Chi square for trend = 0.5, NS). The pattern of increasing CFR with increasing age amongst those who had been independent prestroke was seen particularly in patients with cerebral infarction (Chi square for trend = 8.6, p less than 0.005). The age-adjusted relative risk of death for patients with cerebral infarction who had been functionally dependent pre-stroke was 2.2 (95% confidence interval 1.2 to 4.1). Fifty three percent of all deaths within 30 days of stroke were due to the direct neurological sequelae of the stroke. Patients with primary intracerebral or subarachnoid haemorrhages were significantly more likely to die in this way than those with cerebral infarction (relative risk 4.1; 95% confidence interval 3.4-4.9) and 56% of such deaths occurred within 72 hours of onset. In patients with cerebral infarction, 51% of deaths were due to complications of immobility (for example, pneumonia, pulmonary embolism) and these were more likely to occur after the first week. These findings have implications for clinical practice and the planning of clinical trials.

Aged↗
PubMed1990

Life events and difficulties preceding stroke.

Life events and difficulties were recorded for the year before stroke, using a standardised semi-structured interview, in 113 surviving patients seen after their first ever in a lifetime stroke. An age and sex-matched control group (n = 109) was also interviewed about the preceding year. The stroke patients reported fewer non-threatening events and events with only a short-term threat, while difficulties were reported with equal frequency by the two groups. However, events which were severely threatening in the long-term were significantly more common in the stroke patients (in the 52 weeks before stroke 26% versus 13%, odds ratio 2.3, 95% confidence interval 1.1-4.9). The increased rate was apparent throughout the year and not just in the weeks immediately before stroke onset. The number of stroke patients experiencing severe events in the follow up year fell to the level found in the control group. Recognised risk factors for stroke were found equally in those patients with and without severe events before onset, except that hypertension was rather less common in the patients who had experienced a severe event. It therefore appears that severe life events may be one of the determinants of stroke onset.

Adolescent↗
PubMed1990

Prognosis of transient ischemic attacks in the Oxfordshire Community Stroke Project.

In a community-based study of approximately 105,000 people, 184 presented with a transient ischemic attack during the 5 years between 1981 and 1986; we believe these persons represent almost all new cases of transient ischemic attack going to a doctor during that period. During a mean follow-up of 3.7 years 49 patients died, 45 had a first-ever stroke, and 17 had a myocardial infarction. Cardiac disease accounted for 17 (35%) deaths, while stroke was the cause of death in 15 patients (31%). The average actuarial risk of death was approximately 6.3%/yr, slightly greater than that expected for similar people without transient ischemic attacks (risk ratio [observed divided by expected] = 1.4). The actuarial risk of stroke was 11.6% during the first year after a transient ischemic attack and approximately 5.9%/yr over the first 5 years. Patients who suffered a transient ischemic attack had a 13-fold excess risk of stroke during the first year and a sevenfold excess risk over the first 7 years compared with people without transient ischemic attacks. The actuarial risk of death, stroke, or myocardial infarction over the first 5 years after a transient ischemic attack was approximately 8.4%/yr. The prognosis in this community-based cohort was better than that in previous reports. The high early risk of stroke means that investigation and treatment of new cases should commence as soon as possible.

Cerebrovascular Disorders↗
PubMed1990

Epidemiology of deliberate self-poisoning: trends in hospital attendances.

A number of reports have suggested that the incidence of deliberate self-harm has been declining since the late 1970s. Most of these findings have emerged from studies of hospital inpatients, but a large proportion of patients are sent home directly from Accident and Emergency Departments. This study, based in the Nottingham Accident and Emergency Department, looked at attendances for deliberate self-poisoning over four separate years in the period between 1981 and 1988. The findings show a slight reduction over time in the number of attendances and overall rates, with age-specific rates holding steady for the younger age-group (15-34 years), but diminishing as age increases. It is argued that age-specific trends, based on inpatient statistics, could be distorted by Accident and Emergency discharges. It is recommended that future epidemiological studies of deliberate self-harm include patients who progress no further than the Accident and Emergency Department.

Age Factors↗
PubMed1989

Emotionalism after stroke.

OBJECTIVE: To estimate the prevalence of emotionalism after stroke, to assess its relation with other mood disorders, and to identify clinical variables with which it is associated. DESIGN: Descriptive study of a cohort of patients consecutively entered on a community stroke register. SETTING: Community based research project. PATIENTS: A total of 128 patients who had suffered first ever stroke. INTERVENTIONS AND END POINTS: Patients were interviewed by a psychiatrist at 1, 6, and 12 months after stroke. Mood state was assessed by standardised semistructured interview (present state examination) and self report (Beck depression inventory). Intellectual impairment was assessed by mini mental state examination and Frenchay aphasia screening test. In addition, stroke lesions were localised by computed tomography. MAIN RESULTS: Emotionalism was reported by 13 of 89 patients (15%) at one month, 25 of 119 (21%) at six months, and 12 of 112 (11%) at 12 months after stroke. Patients with emotionalism had higher scores on both measures of mood disorder (at 6 months: mean Beck score 10.5 v 6.4; present state examination score 7.2 v 5.1) and more diagnosable psychiatric disorder (at 6 months: 40% v 14%; odds ratio 4.2, 95% confidence interval 1.5 to 11.9). Almost all episodes were provoked by clearly identified and appropriate emotional experiences. Patients with emotionalism also had more intellectual impairment and larger lesions on computed tomography. Lesions in the left frontal and temporal regions were particularly associated with emotionalism: at 6 months 8 of 14 patients (57%) with such lesions had emotionalism compared with 10 of 52 (19%) of those with lesions elsewhere (odds ratio 5.6, 95% confidence interval 1.4 to 22). CONCLUSIONS: Emotionalism is common after stroke. It is neither emotionally meaningless and inappropriate, nor is it found mostly in patients with bilateral brain damage. Emotionalism is associated with symptoms of a more general mood disturbance and is found especially in patients with left frontal and temporal lesions.

Affective Symptoms↗
PubMed1989

Methods of identifying mood disorders in stroke patients: experience in the Oxfordshire Community Stroke Project.

Four simple methods for assessing mood disorders were examined in a cohort of stroke patients: the Beck Depression Inventory; a visual analogue mood scale; a nurses' depression rating; and a carers' depression rating. None of the measures was entirely satisfactory, either because of inaccuracy when compared to a standardized psychiatric interview, or because of low response rates. A review of their case records showed that the patients' general practitioners were aware of nearly all those with severe persistent mood disorders. The implications of these findings for clinical practice are discussed.

Cerebrovascular Disorders↗
PubMed1989

A thrilling case of hiatus hernia.

A 65 year old woman was found to have a left parasternal heave and a systolic murmur associated with a thrill. A chest radiograph, echocardiogram and gastrograffin swallow demonstrated a massive obstructed hiatus hernia which displaced the heart anteriorly. Aspiration of the contents of the hernia led to complete resolution of the physical signs. Possible mechanisms for their production are discussed.

Aged↗
PubMed1988

Amino acids of the Torpedo marmorata acetylcholine receptor alpha subunit labeled by a photoaffinity ligand for the acetylcholine binding site.

The acetylcholine-binding sites on the native, membrane-bound acetylcholine receptor from Torpedo marmorata were covalently labeled with the photoaffinity reagent [3H]-p-(dimethylamino)-benzenediazonium fluoroborate (DDF) in the presence of phencyclidine by employing an energy-transfer photolysis procedure. The alpha-chains isolated from receptor-rich membranes photolabeled in the absence or presence of carbamoylcholine were cleaved with CNBr and the radiolabeled fragments purified by high-performance liquid chromatography. Amino acid and/or sequence analysis demonstrated that the alpha-chain residues Trp-149, Tyr-190, Cys-192, and Cys-193 and an unidentified residue(s) in the segment alpha 31-105 were all labeled by the photoaffinity reagent in an agonist-protectable manner. The labeled amino acids are located within three distinct regions of the large amino-terminal hydrophilic domain of the alpha-subunit primary structure and plausibly lie in proximity to one another at the level of the acetylcholine-binding sites in the native receptor. These findings are in accord with models proposed for the transmembrane topology of the alpha-chain that assign the amino-terminal segment alpha 1-210 to the synaptic cleft. Furthermore, the results suggest that the four identified [3H]DDF-labeled residues, which are conserved in muscle and neuronal alpha-chains but not in the other subunits, may be directly involved in agonist binding.

Acetylcholine↗
PubMed1988

Recognition memory of item, associative and serial-order information after temporal lobectomy for seizure disorder.

Children, adolescents, and young adults with temporal lobectomy judged the context of their encounters with a word (by deciding about its prior occurrence or familiarity) and also identified word attributes involving associative content and serial order (by indicating word meanings and reconstructing word sequences). Laterality of temporal lobectomy was important for identifying familiarity: individuals with right-sided temporal lobectomies made better judgements than those with left resections about the prior occurrence of target words, with the more successful performance depending on enhanced sensitivity to the familiarity or non-familiarity of what was heard. Identifying the attributes of an item, as contrasted with its prior occurrence, depended on aspects of temporal lobe disorder in conjunction with laterality: deficits of brain structure involving histopathology and significant tissue loss disrupted content memory; compromised brain function resulting from certain post-infantile seizures impaired memory for serial order. In the young brain after temporal lobectomy, there exists a functional dissociation between judging the familiarity of an event and identifying its attributes, a dissociation that depends, not only on laterality of surgery, but also on the structural and functional intactness of the residual brain.

Adolescent↗
PubMed1988

A prospective study of acute cerebrovascular disease in the community: the Oxfordshire Community Stroke Project 1981-86. 1. Methodology, demography and incident cases of first-ever stroke.

A prospective study of acute cerebrovascular disease in a community of about 105,000 people is reported. The study protocol combined rapid clinical assessment of patients with accurate diagnosis of the pathological type of stroke by CT or necropsy, whether or not they were admitted to hospital. The study population was defined as those people who were registered with one of 50 collaborating general practitioners (GPs). Referrals to the study were primarily from the GPs though, to ensure complete case ascertainment, hospital casualty and admission registers, death certificates and special data from the Oxford Record Linkage Study were also scrutinized. Six hundred and seventy five cases of clinically definite first-ever in a lifetime stroke were registered in four years yielding a crude annual incidence of 1.60/1,000 or 2.00/1,000 when adjusted to the 1981 population of England and Wales. The age and sex specific incidence rates for first stroke showed a steep rise with age for both sexes. The odds of a male sustaining a first stroke were 26% greater than those of a female. Ninety one per cent of patients were examined in a median time of four days after the event by a study neurologist and 88% had cerebral CT or necropsy.

Adolescent↗