Search PubMed⌕ Search

Biomedical subjects

M M Brown

Publications and source records attributed to M M Brown.

At least 19 recordsLinked to original sources
PubMed2006

Auditory temporal processing deficits in patients with insular stroke.

OBJECTIVE: To assess central auditory function in a series of patients with stroke of the insula and adjacent areas. METHODS: The authors recruited eight patients with stroke affecting the insula and adjacent areas and eight neurologically normal controls (matched to the patients for age, sex, handedness, and hearing thresholds). The lesion spared the adjacent auditory areas in three patients and included other auditory structures in five cases. The authors conducted pure-tone audiometry and tympanometry and a central auditory test battery, which included the dichotic digits, and three temporal tests, the duration pattern, frequency pattern, and gaps in noise tests. They collected information from the hospital notes on symptoms at presentation and neuropsychological assessment data during the acute phase. RESULTS: The central auditory tests gave normal results in all controls. The temporal tests gave abnormal results in all three cases in which other auditory areas were spared, as well as in the other five cases. Results of the gaps in noise test were abnormal contralaterally to the lesion in three and bilaterally in five cases. The central auditory deficits did not cosegregate with the presence of cognitive impairment during the acute stage. CONCLUSION: Insular lesions may affect central auditory function and, in particular, temporal resolution and sequencing, consistent with neuroimaging studies.

Adult↗
PubMed2006

Phase 1 trial of the antiangiogenic peptide ATN-161 (Ac-PHSCN-NH(2)), a beta integrin antagonist, in patients with solid tumours.

To evaluate the toxicity, pharmacological and biological properties of ATN-161, a five -amino-acid peptide derived from the synergy region of fibronectin, adult patients with advanced solid tumours were enrolled in eight sequential dose cohorts (0.1-16 mg kg(-1)), receiving ATN-161 administered as a 10-min infusion thrice weekly. Pharmacokinetic sampling of blood and urine over 7 h was performed on Day 1. Twenty-six patients received from 1 to 14 4-week cycles of treatment. The total number of cycles administered to all patients was 86, without dose-limiting toxicities. At dose levels above 0.5 mg kg(-1), mean total clearance and volume of distribution showed dose-independent pharmacokinetics (PKs). At 8.0 and 16.0 mg kg(-1), clearance of ATN-161 was reduced, suggesting saturable PKs. Dose escalation was halted at 16 mg kg(-1) when drug exposure (area under the curve) exceeded that associated with efficacy in animal models. There were no objective responses. Six patients received more than four cycles of treatment (>112 days). Three patients received 10 or more cycles (> or =280 days). ATN-161 was well tolerated at all dose levels. Approximately, 1/3 of the patients in the study manifested prolonged stable disease. These findings suggest that ATN-161 should be investigated further as an antiangiogenic and antimetastatic cancer agent alone or with chemotherapy.

Adult↗
PubMed2005

Cerebral microbleeds are common in ischemic stroke but rare in TIA.

BACKGROUND: In patients with stroke, gradient-echo MRI commonly detects microbleeds, indicating small artery disease with increased risk of macroscopic intracranial bleeding. Antithrombotic treatments are frequently prescribed after TIA and stroke, but there have been no previous studies of microbleeds in TIA. Because microbleeds may predict the hemorrhagic risk of antithrombotic treatments, we studied the prevalence of microbleeds, risk factors, and pathophysiologic mechanisms in patients with ischemic stroke and TIA. METHODS: One hundred twenty-nine consecutive patients with ischemic stroke or TIA were studied with MRI including T2, fluid-attenuated inversion recovery, and gradient-echo MRI sequences. Blinded observers counted microbleeds and graded white matter T2 hyperintensities throughout the brain. TIA patients with previous ischemic stroke were excluded. RESULTS: Sixty-seven percent of patients had ischemic stroke; 33% had TIA. Microbleeds were found in 23% of ischemic stroke patients but only 2% of TIA patients (p < 0.001). There were no significant differences in conventional risk factors or the severity of white matter disease on T2 MRI between stroke and TIA patients. Patients with microbleeds were more often hypertensive (81 vs 59%; p = 0.04) and had more severe MRI white matter disease on T2 MRI (p = 0.003). CONCLUSIONS: Microbleeds are common in ischemic stroke but rare in TIA, an observation not explained by differences in vascular risk factors or severity of white matter disease seen on T2 MRI. This finding has implications for the safety of antithrombotic therapy and clinical trial design in the two groups. Microbleeds may also be a new marker for severe microvascular pathology with increased risk of permanent cerebral infarction.

Aged↗
PubMed2005

Percutaneous transluminal angioplasty and stenting for vertebral artery stenosis.

BACKGROUND: Surgery for vertebral artery stenosis is technically difficult, potentially hazardous and is not considered in most centres. There is growing evidence from case series that vertebral artery stenosis may be treated endovascularly by percutaneous transluminal angioplasty and stenting. This may be a feasible alternative to surgery to relieve symptoms caused by significant stenosis. OBJECTIVES: The objective of this review was to assess the safety and efficacy of vertebral artery percutaneous transluminal angioplasty, with or without stenting, combined with medical care, compared to medical care alone, in patients with vertebral artery stenosis. SEARCH STRATEGY: We searched the Cochrane Stroke Group's trials register (last searched 28 July 2004). In addition we searched the following bibliographic databases: Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 3, 2002), MEDLINE (1966 to July 2004), EMBASE (1980 to July 2004), and Science Citation Index (1981 to July 2004). We also contacted researchers in the field, and balloon catheter and stent manufacturers. SELECTION CRITERIA: We selected randomised trials of endovascular treatment of vertebral artery stenosis combined with best medical therapy, compared with best medical therapy alone, in patients with symptomatic or asymptomatic vertebral artery stenosis. DATA COLLECTION AND ANALYSIS: Two reviewers independently applied the inclusion criteria, extracted data and assessed trial quality. MAIN RESULTS: One completed randomised trial was found. In one subgroup of this trial, 16 patients with symptomatic severe vertebral artery stenosis were randomised to endovascular treatment (n = 8) or medical treatment alone (n = 8). There were no strokes in any arterial territory or deaths from any cause in either group within 30 days of treatment (endovascular group) or 30 days of randomisation (medical group). In the endovascular group, two patients had a posterior circulation TIA at the time of the procedure. In the endovascular group, the mean vessel stenosis at follow up was 47% (range 0% to 80%). Patients were followed up for a mean of 4.5 years in the endovascular group and 4.9 years in the medical group. There were no further vertebrobasilar territory strokes in either group for the duration of follow up. Morbidity and mortality was related to carotid and coronary artery disease in this study. AUTHORS' CONCLUSIONS: There is currently insufficient evidence to assess the effects of percutaneous transluminal angioplasty with or without stenting or primary stenting for vertebral artery stenosis.

Angioplasty, Balloon↗
PubMed2005

Increased platelet count and leucocyte-platelet complex formation in acute symptomatic compared with asymptomatic severe carotid stenosis.

OBJECTIVE: The risk of stroke in patients with recently symptomatic carotid stenosis is considerably higher than in patients with asymptomatic stenosis. In the present study it was hypothesised that excessive platelet activation might partly contribute to this difference. METHODS: A full blood count was done and whole blood flow cytometry used to measure platelet surface expression of CD62P, CD63, and PAC1 binding and the percentage of leucocyte-platelet complexes in patients with acute (0-21 days, n = 19) and convalescent (79-365 days) symptomatic (n = 16) and asymptomatic (n = 16) severe (> or =70%) carotid stenosis. Most patients were treated with aspirin (37.5-300 mg daily) although alternative antithrombotic regimens were more commonly used in the symptomatic group. RESULTS: The mean platelet count was higher in patients with acute and convalescent symptomatic compared with asymptomatic carotid stenosis. There were no significant differences in the median percentage expression of CD62P and CD63, or PAC1 binding between the acute or convalescent symptomatic and asymptomatic patients. The median percentages of neutrophil-platelet (p = 0.004), monocyte-platelet (p = 0.046), and lymphocyte-platelet complexes (p = 0.02) were higher in acute symptomatic than in asymptomatic patients. In patients on aspirin monotherapy, the percentages of neutrophil-platelet and monocyte-platelet complexes (p = 0.03) were higher in acute symptomatic (n = 11) than asymptomatic patients (n = 14). In the convalescent phase, the median percentages of all leucocyte-platelet complexes in the symptomatic group dropped to levels similar to those found in the asymptomatic group. CONCLUSION: Increased platelet count and leucocyte-platelet complex formation may contribute to the early excess risk of stroke in patients with recently symptomatic carotid stenosis.

Acute Disease↗
PubMed2004

Percutaneous transluminal angioplasty and stenting for carotid artery stenosis.

BACKGROUND: Carotid artery stenosis may be treated endovascularly by percutaneous transluminal balloon angioplasty with or without stent insertion or by primary stenting. Endovascular treatment may be a useful alternative to carotid endarterectomy (CEA), particularly for lesions not suitable for surgery. OBJECTIVES: The objective of this review was to assess the benefits and risks of endovascular treatments compared with carotid endarterectomy (in patients suitable for surgery) or medical therapy (in patients not suitable for surgery). SEARCH STRATEGY: We searched the Cochrane Stroke Group trials register (last searched 1 September 2003). In addition we searched the following bibliographic databases: Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 3, 2002), MEDLINE (1966 to June 2003), EMBASE (1980 to June 2003) and Science Citation Index (1981 to June 2003). We also contacted researchers in the field and balloon catheter and stent manufacturers. SELECTION CRITERIA: We selected randomised trials of carotid endovascular treatment compared with carotid endarterectomy, or endovascular treatment plus best medical therapy compared with best medical therapy alone, in patients with symptomatic or asymptomatic carotid artery stenosis. DATA COLLECTION AND ANALYSIS: Two reviewers independently applied the inclusion criteria, extracted data and assessed trial quality. MAIN RESULTS: Two completed trials comparing endovascular treatment with carotid endarterectomy involving 608 patients were found. In addition there were two trials which fulfilled the inclusion criteria and which were stopped early (242 patients), and a third trial which has completed randomisation and 30 day follow up of 307 patients. Four trials are ongoing. Meta analysis of the data from the included studies found no significant difference between the odds of death or any stroke at 30 days post procedure (Odds Ratio [OR] endovascular:surgery 1.26, 95% Confidence Interval [CI] 0.82 to 1.94). The odds of death or disabling stroke at 30 days were similar in the endovascular and surgical group (OR 1.22, CI 0.61 to 2.41). At one year following procedure, there was no significant difference between the two groups in preventing any stroke or death (OR 1.36,CI 0.87 to 2.13). Endovascular treatment significantly reduced the risk of cranial neuropathy (OR 0.12, CI 0.06 to 0.25). There was no significant difference between the two groups when the risk of death, any stroke or myocardial infarction was considered (OR 0.99, CI 0.66 to 1.48). There was substantial heterogeneity between the trials for four of the five outcomes. REVIEWERS' CONCLUSIONS: Data from randomised trials comparing endovascular treatment for carotid artery stenosis with carotid endarterectomy suggest that the two treatments have similar early risks of death or stroke and similar long term benefits. However, the substantial heterogeneity renders the overall estimates of effect somewhat unreliable. Furthermore, two trials were stopped early because of safety concerns, so perhaps leading to an over-estimate of the risks of endovascular treatment. On the other hand, endovascular treatment appears to avoid completely the risk of cranial neuropathy. There is also uncertainty about the potential for restenosis to develop and cause recurrent stroke after endovascular treatment. The current evidence does not support a widespread change in clinical practice away from recommending carotid endarterectomy as the treatment of choice for suitable carotid artery stenosis. There is a strong case to continue recruitment in the current randomised trials comparing carotid stenting with endarterectomy.

Angioplasty, Balloon↗
PubMed2004

Combining a targeted radiotherapy and gene therapy approach for adenocarcinoma of prostate.

A targeted radiotherapy/gene therapy approach for prostate cancer, using the radiopharmaceutical [(131)I]meta-iodobenzylguanidine ([(131)I]MIBG), would restrict the effects of radiotherapy to malignant cells, thereby increasing efficacy and decreasing morbidity of radiotherapy. Prostate cancer cells were transfected with a transgene encoding the noradrenaline transporter (NAT) under the control of tumour-specific telomerase promoters, enabling them to actively take up [(131)I]MIBG. This led to tumour-specific cell kill. This strategy has the advantage of generating a radiological bystander effect, leading to the destruction of neighbouring tumour cells that have escaped transfection. This targeted approach could be a promising tumour-specific treatment option for prostate cancer.

3-Iodobenzylguanidine↗
PubMed2004

A study of acute rehabilitation after head injury.

In 1999 a report from the Royal College of Surgeons of England drew attention to the fact that, in the UK, there is little structured acute inpatient rehabilitation for patients admitted after traumatic brain injury (TBI). This paper reports the results of a retrospective study of acute inpatient rehabilitation (AR) after TBI, comparing aspects of resource use in 92 patients who received structured unit-based multidisciplinary AR with 97 patients who received usual practice. About 10% of patients admitted via casualty after TBI required AR after neurosurgical consultation or care. These patients remained in AR for a mean of 20.5 days; length of stay in an acute bed was not prolonged compared with patients in usual practice. Sixty per cent of patients discharged home from unit-based care were referred to community-based rehabilitation on discharge compared with no patients discharged home from neurosurgical care. There is an urgent need to discuss and plan at national level the structured secondary provision of acute rehabilitation after acquired brain injury.

Adult↗
PubMed2004

Guidelines on the management of secondary prophylaxis of vascular events in stable patients in primary care.

Atherothrombosis, thrombus formation superimposed on an existing atherosclerotic plaque, is an acute process leading to ischaemic events such as myocardial infarction, stroke and critical limb ischaemia. Patients presenting with clinical conditions associated with atherothrombosis are at increased risk of subsequent vascular events. The beneficial effect of antiplatelet therapies for short-term and long-term secondary prevention of atherothrombotic events has been established. These guidelines aim to provide evidence-based recommendations that will assist in the antiplatelet-mediated secondary prophylaxis of vascular events in patients with stable cardiovascular disease treated in the primary healthcare setting. Medline and the Cochrane library were accessed using free-text strategies in the domains of antiplatelet agents and antithrombotics. Development of the guidelines was driven by a series of Steering Committee meetings, in which the quality of relevant studies was assessed and identified using narrative summary. These guidelines present evidence and recommendations for the treatment of numerous atherothrombotic indications depending on individual patient circumstances.

Acute Disease↗
PubMed2003

Neural correlates of motor recovery after stroke: a longitudinal fMRI study.

Recovery of motor function after stroke may occur over weeks or months and is often attributed to cerebral reorganization. We have investigated the longitudinal relationship between recovery after stroke and task-related brain activation during a motor task as measured using functional MRI (fMRI). Eight first-ever stroke patients presenting with hemiparesis resulting from cerebral infarction sparing the primary motor cortex, and four control subjects were recruited. Subjects were scanned on a number of occasions whilst performing an isometric dynamic visually paced hand grip task. Recovery in the patient group was assessed using a battery of outcome measures at each time point. Task-related brain activations decreased over sessions as a function of recovery in a number of primary and non-primary motor regions in all patients, but no session effects were seen in the controls. Furthermore, consistent decreases across sessions correlating with recovery were seen across the whole patient group independent of rate of recovery or initial severity, in primary motor cortex, premotor and prefrontal cortex, supplementary motor areas, cingulate sulcus, temporal lobe, striate cortex, cerebellum, thalamus and basal ganglia. Although recovery-related increases were seen in different brain regions in four patients, there were no consistent effects across the group. These results further our understanding of the recovery process by demonstrating for the first time a clear temporal relationship between recovery and task-related activation of the motor system after stroke.

Adult↗
PubMed2003

Neural correlates of outcome after stroke: a cross-sectional fMRI study.

Recovery of motor function after stroke may occur over weeks or months and is often attributed to neuronal reorganization. Functional imaging studies investigating patients who have made a good recovery after stroke have suggested that recruitment of other motor-related networks underlies this recovery. However, patients with less complete recovery have rarely been studied, or else the degree of recovery has not been taken into account. We set out to investigate the relationship between the degree of recovery after stroke and the pattern of recruitment of brain regions during a motor task as measured using functional MRI. We recruited 20 patients who were at least 3 months after their first ever stroke, and 26 right-handed age-matched control subjects. None of our patients had infarcts involving the hand region of the primary motor cortex. All subjects were scanned whilst performing an isometric, dynamic visually paced handgrip task. The degree of functional recovery of each patient was assessed using a battery of outcome measures. Single-patient versus control group analysis revealed that patients with poor recovery were more likely to recruit a number of motor-related brain regions over and above those seen in the control group during the motor task, whereas patients with more complete recovery were more likely to have 'normal' task-related brain activation. Across the whole patient group and across stroke subtypes, we were able to demonstrate a negative correlation between outcome and the degree of task-related activation in regions such as the supplementary motor area, cingulate motor areas, premotor cortex, posterior parietal cortex, and cerebellum. This negative correlation was also seen in parts of both contralateral and ipsilateral primary motor cortex. These results further our understanding of the recovery process by demonstrating for the first time a clear relationship between task-related activation of the motor system and outcome after stroke.

Adult↗
PubMed2003

Quality of life with macular degeneration: perceptions of patients, clinicians, and community members.

BACKGROUND/AIMS: Age related macular degeneration (ARMD) is a common ophthalmological disorder that can significantly impair a patient's ability to function independently and potentially have a dramatic impact on health related quality of life. The aim of this study is to evaluate the quality of life of patients with ARMD, through the use of utility evaluation, and assess whether clinicians and healthy volunteers appreciate the impact of ARMD on health related quality of life. METHODS: A standardised questionnaire using the time-tradeoff method of utility analysis was created to assess health related quality of life. This questionnaire was distributed to 115 patients with ARMD. A similar questionnaire was distributed to 142 healthy volunteers and 62 clinicians who were asked to assume that they had ARMD. Comparisons were made among the responses from the members of the three groups. RESULTS: There was a significant difference in the utility scores among respondents with mild, moderate, and severe ARMD when compared to members of the general public and clinicians who were asked to assume they had each severity of ARMD. For mild ARMD the mean utility scores were 0.932, 0.960, and 0.832, for the general public, clinicians, and patients respectively (F = 21.7; p <0.001). No significant difference was found between the community members and clinicians (p <0.166); however, the patient group differed significantly from the general public (p<0.001) and clinician (p <0.001) groups. The utility scores for moderate ARMD for the general public, clinicians, and patients were 0.918, 0.877, and 0.732, respectively. (F = 34.6, p <0.001). There was no significant difference between the general public and clinicians (p <0.143); however, the patient group differed significantly compared with the general public (p <0.001) and clinician (p <0.001) groups. The utility scores for people with severe ARMD in the general public, clinician, and patient groups were 0.857, 0.821, and 0.566, respectively (F = 45.5; p <0.001). No significant difference was shown between the community members and clinicians (p <0.386); however, a significant difference was seen when comparing the patient group with the community member and clinician (p<0.001) groups. CONCLUSION: Clinicians and community members may greatly underestimate the impact of mild, moderate, and severe ARMD on health related quality of life.

Adolescent↗
PubMed2003

Utilities associated with diabetic retinopathy: results from a Canadian sample.

BACKGROUND/AIMS: To report patient based utilities, using the time trade-off technique, associated with visual loss secondary to diabetic retinopathy in a sample of Canadian patients. In addition, to compare these utility values with a sample collected in a similar manner in a tertiary care practice in the United States. METHODS: A cross sectional study of eligible patients with diabetic retinopathy presenting to a tertiary facility was performed. Demographic and clinical variables (including Snellen visual acuity), and utilities were collected both through chart review and standardised interviews with diabetic patients. RESULTS: 221 patients with diabetic retinopathy were eligible for this study and completed the interview. The mean age was 63.5 (SD 12.5) years, and 48.4% were female. Over 35% of the sample had visual acuity in the affected eye of 6/60 or worse. The mean utility for the sample was 0.79 (SD 0.23). The mean utility from this sample did not differ significantly from that obtained from a series of patients with diabetic retinopathy who were referred to a tertiary facility in the United States (mean 0.77, SD 0.21, p=0.313). Our cross border comparison had a power of 95% to detect a difference in utility of 0.1 between the two groups. CONCLUSION: On average, Canadian patients with diabetic retinopathy were willing to trade off over 20% of their remaining lifespan in order to eliminate their ocular disease. The mean utility obtained from our sample of Canadian patients with diabetic retinopathy was not statistically different from that obtained from a similar sample of American patients.

Adolescent↗
PubMed2003

Vertebral artery origin angioplasty and primary stenting: safety and restenosis rates in a prospective series.

OBJECTIVES: To report a single centre ongoing experience of endovascular treatment for atherosclerotic vertebral artery origin stenosis in a series of symptomatic patients, with follow up imaging to determine the incidence of restenosis. METHODS: 14 patients with vertebral artery origin stenosis on catheter angiography were treated. Angioplasty without stenting was undertaken in the first four patients, all of whom had follow up catheter angiography at one year. Subsequently, patients were treated by primary stenting and followed up with colour Doppler ultrasound examination. RESULTS: The procedure was technically successful in all treated arteries, with no immediate complications. The degree of stenosis was reduced from (mean (SD)) 73 (18)% before treatment to 21 (26)% immediately after treatment in the angioplasty alone group (p = 0.059). In the primary stenting patients, the severity of stenosis was reduced from 82 (8)% to 13 (13)% immediately after treatment (p < 0.001). Restenosis to 70% or greater occurred at one year in all four patients initially treated by angioplasty without stenting. One patient subsequently developed further symptoms and was retreated by stenting. One of the 10 patients treated by primary stenting developed restenosis. None of the remaining patients had further posterior circulation ischaemic symptoms during a mean follow up period of 33.6 months (range 1 to 72 months). CONCLUSIONS: Restenosis occurs often after vertebral artery origin balloon angioplasty without stenting but is uncommon after stenting. Primary stenting is therefore recommended to maintain patency at this site, and had a low complication rate in this series.

Adult↗
PubMed2002

Validity of the time trade-off and standard gamble methods of utility assessment in retinal patients.

AIM: To assess the validity of the time trade-off (TTO) and standard reference gamble (SRG) techniques of utility assessment in patients with retinal disease. A cross section of eligible patients was studied and validity was determined through their relation with two logical constructs, visual acuity and scores from the Visual Function 14 (VF-14) index. METHODS: The study consisted of eligible patients presenting to a tertiary retinal facility who completed an interview. All patients had best corrected vision of 20/40 or worse in at least one eye. TTO and SRG utilities, as well as a VF-14 questionnaire, were administered through a standardised interview. Demographic and clinical (including Snellen visual acuity) information was also collected. RESULTS: 323 patients met these study criteria. Significant predictors of TTO utilities in the multivariate analysis were vision in the better seeing eye (p<0.01) and VF-14 scores (p<0.01). Significant predictors of standard gamble utilities were also vision in the better seeing eye (p<0.01) and VF-14 scores (p<0.05). CONCLUSION: Both the standard gamble and TTO methods demonstrate strong validity when evaluated against visual acuity in the better seeing eye and the VF-14 score.

Adolescent↗
PubMed2001

Expression in UVW glioma cells of the noradrenaline transporter gene, driven by the telomerase RNA promoter, induces active uptake of [131I]MIBG and clonogenic cell kill.

One of the most effective ways to kill cancer cells is by treatment of tumours with radiation. However, the administered dose of radiation to the tumour is limited by normal tissue toxicity. Strategies which decrease normal tissue exposure relative to tumour dose are urgently sought. One such promising scheme involves gene transfer, leading to the introduction of transporters specific for pharmaceuticals which can be labelled with radionuclides. We have previously demonstrated in vitro, that transfer of the noradrenaline transporter (NAT) gene, under viral promoter control, induces in host cells the active accumulation of the radiopharmaceutical [131I]meta-iodobenzylguanidine ([131I]MIBG) which results in kill of clonogens. We now report 17-fold enhancement of [131I]MIBG uptake by UVW glioma cells transfected with the NAT gene whose expression is driven by the human telomerase RNA (hTR) promoter (70% the uptake achieved by the strong viral promoter). Multicellular spheroids composed of hTR-NAT-transfected UVW cells exhibited dose-dependent susceptibility to treatment with [131I]MIBG. This was demonstrated by decreased survival of clonogens and complete sterilization of clonogens derived from spheroids and also failure of spheroids to regrow after administration of 7 MBq/ml [131I]MIBG. These data suggest hTR regulated expression of NAT may be an effective gene therapy strategy.

3-Iodobenzylguanidine↗