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Biomedical subjects

R A Barker

Publications and source records attributed to R A Barker.

At least 55 records · Page 3Linked to original sources
PubMed2000

Prospects for the treatment of Parkinson's disease using neural grafts.

Parkinson's disease (PD) is an incurable neurodegenerative condition of the central nervous system (CNS) that typically presents in the fifth to seventh decade of life, with a movement disorder that consists of a resting tremor, bradykinesia and rigidity. It is a disease that can only be diagnosed with certainty at postmortem when the pathological hallmark is loss of the dopaminergic nigrostriatal pathway and presence of Lewy bodies in the substantia nigra. However, pathological changes, including Lewy body formation, are found outside of the nigrostriatal system and involve other neurotransmitters, which may also account for some of the cognitive, psychiatric and autonomic abnormalities in these patients. To date, the mainstay of treatment for patients with PD has been drugs that activate the dopaminergic network, namely the dopamine precursor L-dopa and dopamine receptor agonists. However, recently interest has turned towards more curative therapies, including the use of grafts of neural tissue to replace dopaminergic neurones that have been lost. This approach has now entered clinical trials and this review will analyse the therapeutic approach of neural grafting in PD.

Animals↗
PubMed1999

Microangiopathy of the brain and retina with hearing loss in a 50 year old woman: extending the spectrum of Susac's syndrome.

A 50 year old woman presented with a subacute onset of vertigo and diplopia followed by an encephalopathy with confusion, spasticity, ataxia, myoclonus, and multiple branch retinal arteriolar occlusions and unilateral sensorineural deafness. Brain biopsy confirmed multiple microinfarcts with no vasculitis. After the procedure she had a right iliofemoral deep vein thrombosis and was found to be heterozygous for the factor V Leiden mutation. She was treated with anticoagulants and made a marked recovery with no relapses 6 months after presentation. This case extends the age range at which Susac's syndrome can present, and raises the possibility that the condition may be associated with abnormalities of coagulation.

Brain↗
PubMed1998

Posterior communicating artery aneurysm presenting with haemorrhage into an arachnoid cyst.

A patient is reported on with a subarachnoid haemorrhage (SAH) from an aneurysm of the posterior communicating artery, who initially presented with a sentinel bleed into an arachnoid cyst and normal magnetic resonance angiography (MRA) of the intracranial vasculature which led to a delay in diagnosis. Although this is a very rare presentation of a relatively common condition, it is important to recognise the importance of intracystic haemorrhage in such circumstances as well as the limitations of MRA, as a delay in diagnosis may have serious clinical consequences.

Adult↗
PubMed1998

Review of 23 patients affected by the stiff man syndrome: clinical subdivision into stiff trunk (man) syndrome, stiff limb syndrome, and progressive encephalomyelitis with rigidity.

OBJECTIVE: To investigate whether the stiff limb syndrome may be separated from the stiff man syndrome and progressive encephalomyelitis with rigidity on simple clinical grounds, and whether such a distinction has implications for aetiology, treatment, and prognosis. METHODS: Twenty three patients referred over a 10 year period with rigidity and spasms in association with continuous motor unit activity, but without evidence of neuromyotonia, extrapyramidal or pyramidal dysfunction or focal lesions of the spinal cord were reviewed. The patients were divided into those with an acute or subacute illness, leading to death within 1 year, and those with a chronic course. The latter were divided into those in whom rigidity and spasms dominated in the axial muscles, or in one or more distal limbs, at the time of their first assessment. RESULTS: This simple division identified three distinct groups of patients. (1) Progressive encephalomyelitis with rigidity: two patients had a rapidly progressive condition characterised by widespread rigidity which resulted in death within 6 and 16 weeks. One patient had negative anti-GAD and anti-neuronal antibodies, but had markedly abnormal CSF and widespread denervation. The principal pathological findings in this case were a subacute encephalomyelitis which primarily affected the grey matter. In the remaining patient anti-GAD antibodies were not tested, and postmortem was refused. (2) Stiff man syndrome: eight patients had rigidity and painful spasms of the lumbar paraspinal, abdominal, and occasionally proximal leg muscles associated with a lumbar hyperlordosis. There was no involvement of the upper limbs, distal lower limbs, sphincters or cranial nerves. Seven had anti-GAD antibodies and most had additional evidence of autoimmune disease. Neurophysiologically there was continuous motor unit activity with abnormal exteroceptive reflexes, but a normal interference pattern during spasms. The patients all responded to baclofen/diazepam and remained ambulant. (3) Stiff limb syndrome: thirteen patients had rigidity, painful spasm, and abnormal postures of the distal limb, ususphincter or brainstem involvement. Generalised myoclonic jerks were not a feature. Only two had truncal rigidity, and another two had anti-GAD antibodies. Most had no evidence of autoimmune disease. Neurophysiologically they had continuous motor unit activity in the affected limb, abnormal exteroceptive reflexes, and abnormally segmented EMG activity during spasms. The disease ran a protracted course, and most patients had only a partial response to baclofen or diazepam. About half became wheelchair bound. CONCLUSIONS: The stiff limb syndrome seems distinct from the stiff man syndrome or progressive encephalomyelitis with rigidity, and is an important cause of rigidity and spasm in the setting of continuous motor unit activity.

Adult↗
PubMed1996

The time course of loss of dopaminergic neurons and the gliotic reaction surrounding grafts of embryonic mesencephalon to the striatum.

Grafts of embryonic ventral mesencephalic tissue placed in the striatum of 6-hydroxydopamine-lesioned rats survive, and make and receive connections to and from the host brain. The dopaminergic neurons of the graft can grow processes into the host brain, and thereby alleviate many of the behavioral deficits of this form of experimental Parkinson's disease. However, when examined some weeks after implantation, grafted substantia nigra only contains about 5% of the expected complement of dopaminergic neurons. We have examined the time course of loss of grafted neurons. We find that the majority die during the first 7 days after transplantation. However, we have shown previously that three-dimensional cultures with the same dimensions as a graft, made of identical cell suspensions, have much better dopaminergic neuronal survival. There must, therefore, be features in the environment surrounding a graft that are toxic to dopaminergic neurons. A limiting factor in the efficacy of dopaminergic grafts is the small distance over which the neurons are able to grow neurites and form connections in the host brain. We find that the growth of neurites from dopaminergic neurons into the host striatum occurs in two phases. Neurites reach their maximum length within 7 days of transplantation, and this is followed by a much slower process of branch and terminal formation. Since axon growth in the adult brain may be inhibited by a number of factors associated with reactive gliosis, we have immunostained various ages of graft for vimentin, tenascin, chondroitin sulfate proteoglycan (CS-PG) using the CS56 antibody, the DSD-1 proteoglycan, and microglia using the OX-42 antibody. We have compared this staining with that surrounding a simple stab wound. Vimentin staining was initially seen in the graft and in astrocytes immediately surrounding it. By 7 weeks staining was restricted to a ring of astrocytes surrounding the graft. Tenascin, DSD-1, and CS-PG were initially seen in and around the grafts. By 7 weeks they had disappeared from grafts, but CS-PG and tenascin persisted in small amounts around stab wounds. In general, immunostaining of these molecules persisted longer around a stab lesion than around a graft. There was also an intense local microglial reaction surrounding both grafts and stab wounds which had largely resolved by 7 weeks.

Animals↗
PubMed1995

Dopaminergic neuronal survival and the effects of bFGF in explant, three dimensional and monolayer cultures of embryonic rat ventral mesencephalon.

Embryonic substantia nigra cells when transplanted into the striatum can reverse many of the defects of Parkinson's disease. The efficacy of such grafts is compromised by the poor survival of grafted dopaminergic neurones; typically, 3-10% survive transplantation. We used three tissue culture models to identify stages in the procedure for the preparation and insertion of grafts which might be responsible for this cell death and to identify environments in which survival is optimised. (1) The ventral mesencephalon was dissected from the donor brain, then placed immediately into culture contained in a collagen gel. (2) The dissected tissue fragments were enzymatically dissociated, then the cells placed into monolayer culture. (3) Enzymatically dissociated tissue was packed into 0.5-mm-diameter porous tubes, to simulate the compaction of cells into a graft deposit in the host brain. Dissociation of the tissue by itself caused the death of approximately 30% of dopaminergic neurones, as judged by the difference in cell counts between the intact embryonic day 14 (E14) mesencephalon, and cells dissociated then packed into tubes. Of the dissociated neurones approximately 60% died during the first 24 h and 87% during the first 3 days in monolayer culture, while only 7% of dopaminergic neurones in three-dimensional cultures and 11% of neurones in explant cultures died over the first 3 days. Embryonic dopaminergic neurones are clearly very vulnerable to adverse conditions during the first days after their removal from the donor brain. The excellent survival of neurones in three-dimensional and explant cultures indicates that close association with other cells, which may provide greatly improved access to trophic factors, can enable the cells to survive this period of vulnerability. In contrast to its effects in monolayer cultures, bFGF had no effect on dopaminergic neuronal survival in either explant or three-dimensional cultures.

Animals↗
PubMed1990

Surgical intervention for drug-resistant ventricular tachycardia.

Endocardial resection was required in 26 patients with sustained drug-resistant ventricular tachycardia. The early mortality rate (within 30 days after operation) was 12%. Two deaths were the result of low cardiac output, and the third death was related to recurrent ventricular septal defect after septal endocardial resection. The survivors of endocardial resection were followed up from 6 to 92 months (mean 43). There were no recurrences of ventricular arrhythmias, and patients did not require antiarrhythmic drug therapy. The late mortality rate after endocardial resection was 19%. There were two late cardiac-related deaths (unrelated to arrhythmias) and three late deaths from noncardiac causes. Complete endocardial resection successfully ablates drug-resistant ventricular tachycardia, but is associated with an increased perioperative mortality rate in those patients who have severely depressed left ventricular function without a well defined left ventricular aneurysm.

Adult↗
PubMed1990

Metastatic non-seminomatous germ cell tumour and dermatomyositis.

Twenty to thirty percent of cases of dermatomyositis in adults are associated with malignancy. We report a case in which dermatomyositis heralded the development of a testicular germ cell tumour. Germ cell testicular tumours are treatable and our case emphasizes the importance of measuring blood levels of beta-human chorionic gonadotrophin and alpha-fetoprotein and examination of the testes in young males with indications of possible malignancy.

Adult↗
PubMed1988

Paediatric gastroenteritis in the eastern Malaysian state of Sarawak: an epidemiological and clinical study.

Over a period of 2 months, 35 of 69 (51%) cases of juvenile diarrhoea studied in eastern Malaysia were associated with rotavirus excretion; rotavirus associated diarrhoea occurred most commonly in the 6-24 month age group. Polyacrylamide gel electrophoresis (PAGE) of genome ribonucleic acid showed that only 4 rotavirus electropherotypes could be detected. Of those, 2 predominated and 2 were detected only once each; one of these may have been a reassortment of the two predominant electropherotypes. Analysis of the clinical features of patients excreting rotavirus subgroup 1 or 2, determined by PAGE, demonstrated that rotavirus subgroup 1 was associated with more hypotonic dehydration and need for intravenous therapy: lethargy was significantly more common among those excreting rotavirus subgroup 2.

Child, Preschool↗