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Biomedical subjects

M D Shaw

Publications and source records attributed to M D Shaw.

At least 19 recordsLinked to original sources
PubMed2000

Spontaneous chronic and subacute subdural haematoma in young adults.

Spontaneous subacute and chronic haematoma in young adults is rare. It has not been previously reported in this age group. We present three cases of chronic and subacute subdural haematoma in young adults, in one of whom the diagnosis was certainly delayed. All three patients underwent burrhole evacuation and made a full neurological recovery. A cause for the haematoma was never established. The literature on the subject, which is scanty, is reviewed and the condition is briefly discussed. The aetiology remains obscure.

Adult↗
PubMed2000

Efficacy and safety of the endothelin, receptor antagonist TAK-044 in treating subarachnoid hemorrhage: a report by the Steering Committee on behalf of the UK/Netherlands/Eire TAK-044 Subarachnoid Haemorrhage Study Group.

OBJECT: Delayed cerebral ischemia remains an important cause of death and disability in patients who have suffered subarachnoid hemorrhage (SAH). Endothelin (ET) has a potent contractile effect on cerebral arteries and arterioles and has been implicated in vasospasm. The authors administered ET(A/B) receptor antagonist (TAK-044) to patients suffering from aneurysmal SAH. They then assessed whether this agent reduced the occurrence of delayed cerebral ischemic events and examined its safety profile in this group of patients. METHODS: Four hundred twenty patients who had suffered an SAH were recruited into a multicenter, randomized, double-blind, placebo-controlled, parallel-group phase II trial. The primary end point was whether a delayed ischemic event occurred within 3 months after the first dose of the study drug and the secondary end points included determining whether a delayed ischemic event occurred by 10 days after the first dose of the study drug, whether a new cerebral infarct was demonstrated on a computerized tomography scan or at postmortem examination by 3 months after administration of the initial dose, the patient's Glasgow Outcome Scale scores at 3 months after the initial dose, and adverse events. There was a lower incidence of delayed ischemic events at 3 months in the TAK-044-treated group: 29.5% compared with 36.6% in a group of patients receiving placebo. The estimated relative risk was 0.8 with a 95% confidence interval of 0.61 to 1.06. There were no significant differences in the secondary end points, including clinical outcomes in the placebo-treated and TAK-044-treated groups. CONCLUSIONS: The TAK-044 was well tolerated by patients who had suffered an SAH, even though hypotension and headache--side effects compatible with the drug's vasodilatory properties--occurred. It would be valuable to proceed to a fully powered phase III trial of an ET receptor antagonist in treating aneurysmal SAH.

Adult↗
PubMed1999

Head injuries in four British neurosurgical centres.

An issue in the design of trials in traumatic brain injury is whether variation amongst centres in 'conventional' management could mask the impact of a powerful new pharmacological agent. We report the results of an observational study of 988 patients admitted to one of four British neurosurgical units between 1986 and 1988 within 3 days of a severe head injury. The centres fell into two pairs on the basis of the 'intensity' of management. In Edinburgh and Southampton, more frequent use of intracranial pressure monitoring, ventilation and osmotic diuretics was made than in Glasgow and Liverpool. The odds ratio for an independent outcome at 6 months in Edinburgh or Southampton, relative to Glasgow or Liverpool, controlling for case mix, was 1.43 (95% CI, 1.03-1.98, p = 0.033). Thus, there is weak evidence of an association between the approach to management and clinical outcome at 6 months.

Accidents, Traffic↗
PubMed1998

A peptide mimic of a protective epitope of respiratory syncytial virus selected from a combinatorial library induces virus-neutralizing antibodies and reduces viral load in vivo.

Respiratory syncytial virus (RSV) is the most important cause of bronchiolitis and pneumonia in infants and young children worldwide. As yet, there is no effective vaccine against RSV infection, and previous attempts to develop a formalin-inactivated vaccine resulted in exacerbated disease in recipients subsequently exposed to the virus. In the work described here, a combinatorial solid-phase peptide library was screened with a protective monoclonal antibody (MAb 19) to identify peptide mimics (mimotopes) of a conserved and conformationally-determined epitope of RSV fusion (F) protein. Two sequences identified (S1 [HWYISKPQ] and S2 [HWYDAEVL]) reacted specifically with MAb 19 when they were presented as solid-phase peptides. Furthermore, after amino acid substitution analyses, three sequences derived from S1 (S1S [HWSISKPQ], S1K [KWYISKPQ], and S1P [HPYISKPQ]), presented as multiple antigen peptides (MAPs), also showed strong reactivity with MAb 19. The affinity constants of the binding of MAb 19, determined by surface plasmon resonance analyses, were 1.19 x 10(9) and 4.93 x 10(9) M(-1) for S1 and S1S, respectively. Immunization of BALB/c mice with these mimotopes, presented as MAPs, resulted in the induction of anti-peptide antibodies that inhibited the binding of MAb 19 to RSV and neutralized viral infection in vitro, with titers equivalent to those in sera from RSV-infected animals. Following RSV challenge of S1S mimotope-immunized mice, a 98.7% reduction in the titer of virus in the lungs was observed. Furthermore, there was a greatly reduced cell infiltration in the lungs of immunized mice compared to that in controls. These results indicate the potential of peptide mimotopes to protect against RSV infection without exacerbating pulmonary pathology.

Animals↗
PubMed1998

Local delivery of cytokines by retrovirally transduced antigen-specific TCR+ hybridoma cells in experimental autoimmune encephalomyelitis.

Autoimmune diseases in humans represent an immune attack on self tissue. Current therapies for almost all autoimmune diseases utilize potent and nonspecific immunosuppressive regimens. These therapies are complicated by their side effects and also place the patient at increased risk for opportunistic infections and malignancies. Our current understanding of immune mechanisms underlying autoimmune diseases remains limited. Ongoing studies include identifying genes that predispose an individual to developing autoimmunity, identification of autoantigens that trigger or perpetuate autoimmunity, and studies of immune cell interactions that lead to immune response. Although it may be many years before a full understanding of autoimmunity is obtained, treatment in animal models of autoimmune disease and some human clinical trials have begun to study alternative treatment approaches to therapy of autoimmune disease. Future therapies for autoimmune diseases should target the inappropriate autoimmune response. This article will describe the use of gene therapy in the treatment of autoimmune disease. We believe that autoimmunity can be ameliorated by delivering trans-acting immunoregulatory molecules by retrovirally transduced autoantigen specific T cells that home to lesions of autoimmunity. Until recently, there has not been a practical alternative to systemic delivery of immunoregulatory molecules, however systemic delivery suffers from toxic side effects and dangerous global immunosuppression. In order to study immune regulation using retroviral transduction for local delivery of immunoregulatory products, we used myelin basic protein (MBP) reactive T cell hybridomas in the murine model of multiple sclerosis (MS), experimental allergic encephalomyelitis (EAE). In this report, we show that MBP reactive T cell hybridomas transduced to express IL-4 or TNF, ameliorated or exacerbated disease, respectively. Additionally, the effects of these cells were dependent on T cell receptor (TCR) expression, indicating that the effects were due to homing of the T cells and the local delivery of cytokines. We believe that gene therapy, allowing local delivery of immunoregulatory proteins by autoantigen specific T cells, represents an interesting potential therapy for autoimmune disease.

Adoptive Transfer↗
PubMed1997

How many higher neurosurgical trainees shall we train in the British Isles?

In the British Isles there are a small number of neurosurgeons. The number of career trainees has been rigorously controlled over the years, such that there is a sufficient number to satisfy the number of new consultants required as the result of retirement and the creation of new posts. The number of career trainees posts is 89 but the current calculated requirement is for 112 career trainees. In addition overseas trainees come to the British Isles, usually for a specific part of their training.

Cross-Cultural Comparison↗
PubMed1994

Comparison of magnetic resonance angiography, duplex ultrasound, and digital subtraction angiography in assessment of extracranial internal carotid artery stenosis.

The results of a prospective study comparing ultrasound, intra-arterial digital subtraction angiography, and magnetic resonance angiography in the assessment of the degree of extracranial internal carotid artery stenosis are reported in patients with symptoms of recent carotid territory ischaemia. A total of 70 patients and 137 vessels were examined by all three techniques. The results obtained by each technique were reported blind. The mean difference (SD) for the comparison of magnetic resonance angiography and digital subtraction angiography was -0.7 (14)%, for ultrasound and digital subtraction angiography 3.1 (15)%, and for magnetic resonance angiography and ultrasound -3.8 (15)%. The level of agreement was greater for the more tightly stenosed vessels. With the assumption that the results of the digital subtraction angiogram reflect the true situation, the sensitivity and specificity in the detection of > or = 30% stenoses were 93% and 82% with ultrasound and 89% and 82% with magnetic resonance angiography; for stenoses > or = 70% 93% and 92% with ultrasound and 90% and 95% with magnetic resonance angiography; and for stenoses of 70-99% 89% and 93% with ultrasound and 86% and 93% with magnetic resonance angiography. For occlusion the values were 93% and 99% with ultrasound and 80% and 99% with magnetic resonance angiography. Increased sensitivity and specificity were obtained when analysis was confined to those vessels in which ultrasound and magnetic resonance angiography were in agreement over classification. It is thus possible to accurately categorize the degree of stenosis of the extracranial internal carotid artery from a combination of ultrasound and magnetic resonance angiography. The adoption of this combination for the investigation of patients before carotid endarterectomy removes the risk associated with conventional angiography and represents an important advance in the management of carotid stenosis.

Adult↗
PubMed1993

Does prediction of outcome alter patient management?

A patient's prognosis is a key factor for the clinicians involved in management. We set out to determine if provision of computer-based predictions of outcome after severe head injury resulted in measurable changes in patient management. In particular, we wondered whether introduction of the predictive system would alter the relation between severity of injury and "intensity" of management. 1025 patients admitted to four British neurosurgical units between 1986 and 1989 following a severe head injury, and who were either in coma for 6 h or had an operation for acute intracranial haematoma, were studied. Specified aspects of intensive management were recorded and all patients were followed up after six months. The study had three phases: a baseline period of at least one year before the introduction of computer-based outcome prediction, one year when predictions were provided at specified times, and a final six months when prediction was withdrawn. While predictions were being provided, there was an increase in the use of specified aspects of intensive care in patients predicted to have a good outcome, but a 39% reduction in the use of these same aspects of intensive care in patients predicted to have the worst outcome. There was no evidence that the provision of predictions affected overall outcome, length of stay, or the recording of explicit decisions to limit treatment. We have demonstrated that the introduction of a routine prediction service can alter patient management.

Adult↗
PubMed1993

Oncocytic variant of choroid plexus papilloma. Evolution from benign to malignant "oncocytoma".

BACKGROUND: The case of a left temporoparietal choroid plexus papilloma in a 12-year-old girl, which recurred 12 months after subtotal resection and apparent full recovery, is described. METHODS: The two consecutive surgical specimens were studied by light and electron microscopy. RESULTS: The first surgical specimen showed a tumor composed of cells with distended cytoplasm packed with numerous mitochondria characteristic of "oncocytic" change. Thus, tumor was the rare benign oncocytic variant of choroid plexus papilloma. A repeat histologic study of the recurrent tumor 12 months later showed evidence of malignant evolution in the form of multinucleated cells with frequent, often bizarre, mitotic figures. CONCLUSION: A rarely described oncocytic variant of choroid plexus papilloma that showed evidence of evolution from benign to malignant "oncocytoma" is discussed.

Adenoma↗
PubMed1993

Ischaemic deterioration following aneurysmal subarachnoid haemorrhage: definition by clinical criteria.

Ischaemia following surgery for aneurysmal subarachnoid haemorrhage (SAH) was defined by clinical criteria. Two distinct groups of patient developing ischaemia were identified: (1) patients recovering from anaesthesia with a new deficit or (2) patients developing 'true' delayed ischaemia. The only significant difference between the groups was an excess of pre-existing vascular disease in the former group. The eventual outcome for patients developing an immediate postoperative deficit was not significantly different from the delayed ischaemia group. The 6-month outcome for patients without clinical ischaemia in the first 10 postoperative days was excellent. The potentially different aetiology of ischaemia in the two subgroups with clinical ischaemia identified in this study should be considered during the planning and in particular the statistical design of trials testing new treatments for clinical ischaemia following aneurysmal SAH.

Adult↗
PubMed1992

Cerebral abscess on Merseyside 1980-1988.

We report a retrospective study of 62 patients presenting to The Walton Centre for Neurology and Neurosurgery with cerebral abscess in the 8-year period between 1980 and 1988. The study shows that while the incidence of cerebral abscess has not altered from the previous decade, aetiological factors have changed and major developments in the diagnosis and management of the condition have resulted in a marked reduction in the morbidity and mortality associated with brain abscess.

Adolescent↗
PubMed1992

Prolactin secreting pituitary carcinoma.

A man with a prolactin secreting pituitary carcinoma was treated by surgery and radiotherapy. Persistent hyperprolactinaemia partially responded to oral bromocriptine for four years. Serum prolactin then rose considerably with rapid, invasive tumour recurrence. Cytotoxic chemotherapy halted tumour progression for twelve months before fatal spread throughout the brain. Failure to normalise serum prolactin with bromocriptine may precede an aggressive course in patients with prolactinoma.

Adult↗
PubMed1992

Development of prognostic index for primary supratentorial intracerebral tumours.

The clinical course of intrinsic supratentorial tumours is variable. Prediction of outcome would be useful in defining patients for specific treatment policies. A retrospective analysis of 560 patients with intrinsic supratentorial tumours was performed. Proportional hazards models for survival were derived by using a stepwise selection procedure with only clinical and CT features as possible explanatory variables. The variables of prognostic importance were age, a first symptom of epilepsy, focal signs at presentation, a cystic lesion on CT scan, and duration of symptoms before presentation. The model defined a group with a good prognosis (score less than or equal to 9, n = 211) and a group with a poor prognosis (score greater than 9, n = 344). The median survival was 27 months for those with a score less than or equal to 9 or less and three months for those with score greater than 9. An alternative model, not including duration of symptoms, is also capable of defining groups with long (score less than or equal to 16, n = 234) and short (score greater than 16, n = 325) survival. The model may provide a means of classifying patients for inclusion in prospective randomised studies.

Actuarial Analysis↗
PubMed1992

Do prophylactic anticonvulsant drugs alter the pattern of seizures after craniotomy?

A total of 276 patients with a high risk of developing postoperative seizures were randomised to treatment with carbamazepine or phenytoin for six or 24 months, or to no treatment. No significant differences were found (though the confidence limits were fairly wide) between the regimes in respect of the incidence of seizures or death. In a substantial proportion of the patients postoperative epilepsy remained a continuing disability. A high incidence of drug-related side effects was found in the treatment groups. Prophylactic anticonvulsants cannot therefore be recommended routinely following supratentorial craniotomy.

Actuarial Analysis↗
PubMed1992

Role of prostaglandins in delayed cerebral ischemia after subarachnoid hemorrhage.

Prostaglandin E2, thromboxane B2, and 6-oxo-prostaglandin F1 alpha were assayed in blood and cerebrospinal fluid samples from patients after subarachnoid hemorrhage (SAH) and from a control population. The levels found in samples obtained from patients after SAH were compared with those found in controls and were also correlated with a number of clinical and radiological variables, many of which are either significantly associated with or represent evidence of cerebral ischemia. The levels of prostaglandin E2, thromboxane B2, and 6-oxo-prostaglandin F1 alpha in blood samples from patients after SAH and from controls were below the level of sensitivity of the assays. Levels of prostaglandin E2, thromboxane B2, and 6-oxo-prostaglandin F1 alpha in cerebrospinal fluid from patients after SAH were significantly elevated when compared with those found in control samples. There was no significant correlation, however, between the level of each prostaglandin measured and the following variables: clinical grade on admission as assessed by the Glasgow Coma Score and the World Federation of Neurological Surgeons grading system; the amount of subarachnoid blood seen on computed tomographic scan; the occurrence of ischemic deterioration; the occurrence of low density change on computed tomographic scan; the presence of vasospasm on angiography; clinical outcome as assessed by the Glasgow Coma Score 3 months after the ictus; and the incidence of ischemia as a cause of death or disability as assessed 3 months after the ictus. A primary role for prostaglandins in the etiology of delayed cerebral ischemia after SAH is not therefore confirmed.

Brain Ischemia↗
PubMed1992

Smoking and subarachnoid haemorrhage: a case control study.

Retrospective and epidemiological studies have suggested that smoking increases the risk of developing aneurysmal subarachnoid haemorrhage (SAH). During 1990, 217 patients presenting to the Mersey Regional Neurosurgical unit with spontaneous SAH were prospectively studied. Smoking habits of patients with SAH were compared with age, sex and occupation matched controls. The relative risk of spontaneous aneurysmal SAH for smokers was twice that of non-smokers (p < 0.001). Management outcome at 6 months following aneurysmal SAH was similar for smokers and non-smokers (p = 0.43) but smokers had more postoperative pulmonary complications requiring ventilation. Significance was tested with chi-square tests.

Adult↗
PubMed1992

Does thrombin prevent cerebral vasospasm following aneurysmal subarachnoid haemorrhage?

Fibrinopeptide A (FPA) levels which have been shown to be a quantitative index of thrombin generation, were measured in blood and cerebrospinal fluid (CSF) samples from patients following subarachnoid haemorrhage (SAH) and from a control population. The levels found in samples obtained in patients following SAH are compared with those found in controls and also correlated with clinical grade on admission as assessed by the Glasgow Coma Score and the World Federation of Neurological Surgeons' grading system, and with the amount of subarachnoid blood seen on CT, the occurrence of ischaemic deterioration, the occurrence of low-density change on CT, the presence of vasospasm on angiography, clinical outcome as assessed by the Glasgow Outcome Score 3 months following the ictus, and the incidence of ischaemia as a cause of death or disability as assessed 3 months following the ictus. The levels of FPA found in blood and CSF from patients following SAH were significantly raised when compared with those found in controls. There was significant correlation between blood FPA levels and the amount of subarachnoid blood seen on initial CT. CSF FPA levels had a statistically significant correlation with outcome as assessed at 3 months post-ictus. No statistically significant correlation was found between blood or CSF FPA levels and any of the other variables studied.

Fibrinopeptide A↗