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Biomedical subjects

R Grant

Publications and source records attributed to R Grant.

At least 73 records · Page 4Linked to original sources
PubMed1997

Neurological paraneoplastic syndromes.

Paraneoplastic neurological syndromes are uncommon, however, their diagnosis is of major practical importance. The identification of antibodies in the serum or cerebrospinal fluid in central nervous system paraneoplastic syndromes confirms the clinical diagnosis of a paraneoplastic syndrome and allows early identification of an underlying tumour at a stage when it is localised and more amenable to treatment. The failure to identify antibodies in patients with characteristic presentations of underlying neurological paraneoplastic syndromes does not exclude an underlying cancer. Necrotising myelopathy, dermatomyositis, and chronic inflammatory demyelinating polyneuropathy all occur more frequently than expected in patients with cancer but autoantibodies have not yet been identified. Although significant advances have been made in diagnosis, further research is needed in the detection of autoantibodies and the elucidation of their role in the aetiology of neurological disease.

Autoantibodies↗
PubMed1997

Limitations of using a cancer registry to identify incident primary intracranial tumours.

The completeness and accuracy of registration of primary intracranial tumours in the Scottish Cancer Registry was compared with a detailed incidence study performed over a two year period (1989-90). Of 228 patients with any primary intracranial tumour in the incidence study, 124 (54%) were identified as intracranial tumours in the cancer registry. The registry excluded benign tumours (although this was not consistent) and so the sensitivity of the registry varied with tumour type (84% for neuroepithelial tumours, 22% meningeal, 29% sellar, 0% cranial nerve). Of the 31 malignant tumours not found in the registry on our initial search, nine were found to have been included between 1989-90 but using different International Classification of Diseases-9th revision (ICD-9) codes or postcodes, and seven were found registered after 1990. Eleven per cent of cases (18/170) identified in the cancer registry were excluded from the incidence study: 11 had evidence of an intracranial tumour before 1989 whereas four definitely did not have an intracranial tumour. The cancer registry therefore significantly underestimated the incidence of all primary intracranial tumours, and of malignant intracranial tumours. Incidence studies must use additional methods to identify all primary tumours. Cancer registries should consider registering all primary intracranial tumours and may improve case ascertainment by screening neuroradiology data.

Brain Neoplasms↗
PubMed1997

Chemotherapy response criteria in malignant glioma.

No one has ever proven a relationship between the extent of response to chemotherapy in malignant glioma and time to progression or survival. We studied the predictive value of "imaging response" following two courses of nitrosourea-based chemotherapy in 136 patients with recurrent astrocytoma/malignant glioma. We performed image analysis by blinded side-to-side comparison of sequential studies, and categorized response into: partial response (PR) (>50% reduction), minor response (MR) (25-50% reduction), stable disease (SD) (<25% change), progressive disease (PD) (>25% increase). Patients with PR, MR, and SD did not differ with respect to time to progression (TTP) (p > 0.2) or survival (p > 0.2). Median TTP was 27 weeks for SD, 43 weeks for MR, and 30 weeks for PR. Patients with PD had a significantly reduced survival (p < 0.001). Median survival was 21 weeks for PD, 53 weeks for SD, 63 weeks for MR, and 48 weeks for PR. The lack of relationship between response and TTP may be due to early relapses in patients with response, a cytostatic benefit of chemotherapy in some patients who do not have an objective response, or a relatively favorable natural history in some tumors that do not respond to chemotherapy. Our data do not support the validity of current response grading, assessed after two courses of chemotherapy. Further research and validation of response criteria is necessary.

Adolescent↗
PubMed1996

The incidence of cerebral glioma in the working population: a forgotten cancer?

We studied the incidence of intracranial tumours in Lothian Region in south-east Scotland in 1989-90. Among 106 patients resident in the Region, 60 (57%) were of working age (15-64 years). All but two cases (97%) were histologically confirmed. The average annual incidence of cerebral glioma in this age range was 5.9 (95% CI 3.8-8.0) per 100,000 per year. Cerebral glioma will affect approximately 2100 people of working age in the UK every year.

Adolescent↗
PubMed1996

Incidence of intracranial tumours in the Lothian region of Scotland, 1989-90.

OBJECTIVE: To determine the incidence of primary and secondary intracranial tumours in the Lothian region of south east Scotland. METHODS: A population based study was performed. Patients from Lothian with incident intracranial tumours diagnosed in 1989 and 1990 (by CT or histology) were identified retrospectively using multiple sources. Differences in incidence by tumour type, age, sex, and socioeconomic status were examined. RESULTS: Four hundred and forty two patients with incident intracranial tumours were identified (228 primary tumours and 214 secondary tumours). The crude yearly incidences of primary and secondary tumours were 15.3 and 14.3 per 100,000 respectively. The commonest primary tumours were neuroepithelial tumours (53.5%), meningeal tumours (19.5%), and sellar tumours (16.5%). About 50% of patients with secondary tumours had an underlying lung cancer. The incidence of primary and secondary tumours increased markedly with age. Meningeal tumours were more common in women, and neuroepithelial tumours were more common in those who lived in more affluent areas. CONCLUSIONS: The incidence rates of primary and secondary intracranial tumours in Lothian were more than twice those previously reported in the United Kingdom. Intracranial tumours are a significant cause of morbidity and mortality in the United Kingdom, and further research into their aetiology and treatment is urgently required.

Adolescent↗
PubMed1996

Cerebral vasculitis following allopurinol treatment.

A 45-year-old man developed cerebral vasculitis associated with a systemic hypersensitivity response shortly after commencing treatment with allopurinol. The illness settled on withdrawal of the drug and no other cause was found.

Allopurinol↗
PubMed1996

Referral pattern and management of patients with malignant brain tumours in south east Scotland.

We reviewed hospital case notes of all incident cases of intracerebral tumours in SE Scotland to analyse referral pattern and time intervals between presentation, diagnosis and treatment. We identified 439 new patients with intracerebral tumours in a two year period: 64% single (primary brain tumours 43%: metastasis 21%) and 36% multiple (metastases). Ninety-two per cent of patients were referred by GP's and 88% were self referrals to hospital or were initially identified at hospital follow-up clinics. Only 27% of patients were initially referred to the specialist centre (Western General Hospital) but 57% were CT scanned at the specialist centre and 83% were referred to there at some time. Time from GP referral to CT scan was related to availability of local CT scanning. Only 10% of cases with probable single metastases and 39% with HGG were treated with surgery plus radiation. Cranial irradiation was started within four weeks of CT diagnosis in 79% of those with metastases but in less than 5% of patients with HGG. The patterns of care for patients with brain tumours show great variation. Hospital referral guidelines, better inter-hospital and inter-department communications and more available access to CT scanning and radiotherapy should improve the quality of care and possibly treatment outcome in this group of patients.

Adolescent↗
PubMed1995

Glutathione S-transferases and cytochrome P450 detoxifying enzyme distribution in human cerebral glioma.

Malignant astrocytomas are frequently resistant to cytotoxic chemotherapy. A possible mechanism of chemoresistance is drug inactivation within malignant astrocytes by detoxifying enzymes (glutathione transferases (GST) and cytochrome P450's). The aim of this study was to assess whether there was differential expression of these detoxifying enzymes in the central nervous system and any relationship to histological grade (WHO) of the tumours. Immunostaining was performed in 30 consecutive glioma samples, using class specific polyclonal antibodies to subtypes of GST (pi, alpha, mu) and to human cytochrome P450 reductase. GST immunostaining was evident in astrocytes and endothelium but not neurones or oligodendrocytes in normal brain. Immunostaining for GST increased in intensity from well differentiated tumours to glioblastoma. Staining was least evident in surrounding normal brain, strong in reactive astrocytes and astrocytic tumour cells and very intense in gemistocytic and giant tumour cells. Small anaplastic tumour cells had very little GST staining. Where endothelial proliferation was evident, GST staining in endothelial cells was increased. Pi was always the predominant subclass, although GST alpha and mu were also expressed in some tumours. Cytochrome P450 reductase immunostaining was present in normal neurones and malignant astrocytes. Gemistocytic astrocytic tumour cells stained intensely. Further work is necessary to see if there is any correlation between immunostaining intensity survival or response to chemotherapy.

Astrocytes↗
PubMed1995

Effects of various isoresistive training programmes on trunk muscle performance.

Isoresistive movements provide a functional method of testing muscle performance and of providing exercise; the resistance applied is usually a percentage of the maximal isometric torque which can be developed by individual subjects. The aim of the current study was to compare the effectiveness of dynamic isoresistive exercise programmes using 25, 50 or 75% of the maximum isometric flexion torque and static isometric exercises for improving the performance of the trunk flexors and extensors. Subjects comprised 42 asymptomatic females aged 18-25 years who were randomly assigned to control or exercise groups. The exercise groups undertook 2 min of exercise 3 times per week. The control subjects showed significant improvement between tests indicating a strong learning effect. The study showed that the subjects who exercised at 50% of maximum flexion isometric torque achieved the greatest increases in muscle performance on most measures. maximal isometric flexion and extension torques did not significantly change in any of the groups. Flexion and extension velocity and power were the muscle performance characteristics which improved the most in response to the training programmes. RELEVANCE:--This paper attempts to determine which among several options is the most effective isoresistive protocol for conditioning trunk muscle performance, as improved strength and power of these muscles may contribute in preventing episodes of LBP.

Journal Article↗
PubMed1995

Analysis of the pharyngoesophageal pressure profile in amyotrophic lateral sclerosis.

Treatment of dysphagia resulting from bulbar amyotrophic lateral sclerosis has included cricopharyngeal myotomy for many years but is successful in only a minority of cases. The purpose of this study was to explore the rationale for this procedure with modern manometric techniques. The results of pharyngoesophageal manometry in 13 patients with amyotrophic lateral sclerosis were compared with 13 age- and sex-matched healthy volunteers by Mann-Whitney analysis. There was no significant difference between patients and control subjects in distal esophageal or lower esophageal sphincter motility nor any pressure parameter of pharyngoesophageal motility. Separate analysis of the seven significantly dysphagic subjects showed a significantly reduced upper esophageal sphincter after-contraction amplitude during water and bread swallows in patients than in control subjects. These data suggest that the dysphagia of amyotrophic lateral sclerosis is not due to upper esophageal sphincter spasm and that treatment by cricopharyngeal myotomy may be inappropriate.

Aged↗
PubMed1995

The effect of tumour associated epilepsy on performance/handicap scales used in cerebral glioma.

The sensitivity of three scales of performance and handicap to the presence and development of epilepsy in patients with brain tumours was studied. Two hypothetical cases had equivalent disability, in one case due to epilepsy and in the other to physical impairment. The second case later developed epilepsy. All consultant neurologists and neurosurgeons in Scotland were asked to grade the cases using three scales commonly used for patients with cerebral glioma. Consultants rated the patient with epilepsy alone as being less disabled and handicapped than the patient with physical impairment without seizures (sign test p < 0.003). At best 21% of clinicians (p = 0.03) were able to report a change in performance score in the second case when seizures developed. These scales do not reflect changes in handicap and performance associated with tumour associated epilepsy. Clinical trial protocols for treatments for brain tumours must state how performance and handicap related to epilepsy will be measured.

Activities of Daily Living↗
PubMed1995

Efficacy of 9-(2-phosphonylmethoxyethyl)adenine treatment against chronic simian immunodeficiency virus infection in macaques.

Long-tailed macaques chronically infected with simian immunodeficiency virus (SIV) were treated for 4 or 8 weeks with daily subcutaneous doses of the antiretroviral compound 9-(2-phosphonylmethoxyethyl)adenine (PMEA). The efficacy of PMEA was evaluated by monitoring cell-free virus in plasma, virus titer and viral DNA in peripheral blood mononuclear cells, and absolute numbers of lymphocyte subsets. In mock-treated control macaques, virus titers changed minimally. However, in treated macaques, PMEA exhibited impressive effects, leading to the disappearance of virus in the blood within the first week of treatment and lasting through the fourth week of treatment. The results indicate that PMEA can effectively reduce SIV in chronically infected macaques and offer an optimistic perspective for therapeutic intervention against human immunodeficiency virus infection.

Adenine↗
PubMed1995

Age influences chemotherapy response in astrocytomas.

OBJECTIVE: In patients with cerebral astrocytomas treated with nitrosourea-based chemotherapy, to determine whether age is predictive of response, time to progression, survival, or rate of complications. DESIGN: Retrospective analysis of neuroimaging studies and clinical data. SETTING: University hospital with a busy neuro-oncology service. PATIENTS: One hundred forty-eight patients with pathologically confirmed malignant astrocytomas or recurrent astrocytomas. RESULTS: Partial response occurred in 39% of patients aged < 40 years, in 17% of those aged 40 to 59, and in only 5% of those aged > or = 60 (p < 0.001). Median time to progression after chemotherapy was 23 weeks in patients aged < 60 and 6 weeks in patients aged > or = 60 (p < 0.001). Median survival after chemotherapy was 43 weeks in patients aged < 60 but only 24 weeks in patients aged > or = 60 (p < 0.001). Differences between age groups in response rate, time to progression, and survival persisted with adjustment for tumor grade. The risk of myelosuppressive complications requiring hospitalization was significantly related to age (p = 0.03); such complications occurred in 35% of patients aged > or = 60 and 16% of patients under 60 years. CONCLUSION: Age is strongly predictive of the likelihood of a response to chemotherapy, time to progression, survival, and risk of myelosuppressive complications. Patients aged > or = 60 have a lower change of benefit and an increased risk of myelosuppressive complications from chemotherapy for astrocytomas compared with younger patients.

Adolescent↗
PubMed1994

Clinical outcome in aggressively treated meningeal carcinomatosis.

OBJECTIVE: To critically evaluate the clinical outcome of patients with cytologically proved meningeal carcinomatosis and to identify factors associated with an improved outcome. DESIGN: A consecutive series of patients was identified from a cytopathology data base. The study period was from 1985 to 1990. Case records and results of radiologic investigations were reviewed; all patients were followed up until their deaths. SETTING: University hospital with a cancer center. PATIENTS: Thirty-six consecutive patients with cytologically proved meningeal carcinomatosis. Patients with lymphoma or leukemia were excluded. INTERVENTIONS: External beam radiation therapy, intrathecal chemotherapy via a ventricular catheter, and intravenous chemotherapy. MAIN OUTCOME MEASURES: Clinical assessment and survival. RESULTS: Symptoms improved in 15% of 33 treated patients. Response to treatment had no clear relationship with the age, site of involvement, or tumor type. Median survival for treated patients was only 9 weeks. Patients who received more than five intrareservoir chemotherapy treatments had a median survival of 23 weeks. Median survival for patients with breast carcinoma who received intravenous chemotherapy was 20 weeks, significantly better than that of patients not receiving intravenous chemotherapy. CONCLUSIONS: Survival is poor despite aggressive treatment. Intravenous chemotherapy may improve survival in patients with chemoresponsive primary tumors and deserves further study.

Adult↗
PubMed1994

Recording neurological impairment in clinical trials of glioma.

The criteria for clinical response to treatment in cerebral glioma remain poorly defined, but could be made more objective if simple measures of neurological impairments were included in the definitions. We assessed the utility of simple fast previously validated tests of limb impairment (Timed nine hole peg test and 10 meter walk), memory (Williams delayed recall test) and language (Boston Aphasia Severity Rating Scale) in fifty patients with primary brain tumours to see if they could act as a surrogate for neurological impairment. The tests were compared with established measures of physical disability (Barthel Disability Index [BDI]) and handicap. Timed tests of hand function and gait were sensitive to minor impairments and were abnormal in patients with physical disability on BDI. Timed tests correlated well with handicap (rank correlation 0.734). Short term memory was impaired more commonly with tumours involving the left hemisphere (p < 0.01). Dysphasia limited testing of memory in 8%. Depression was associated with problems in limb function (p < 0.01), memory (p < 0.001), language (p < 0.001), BDI (p < 0.001) and handicap (p < 0.001). The number of abnormal fast tests also correlated with the severity of handicap (rank correlation 0.786) indicating that memory impairment and aphasia contribute to handicap and should be assessed. Median time to complete all assessments was 7 minutes 20 seconds. Utilization of these simple tests will add sensitivity and objectivity to evaluation of neurological response in clinical trials and can be performed quickly by non medical staff.

Adolescent↗
PubMed1994

Metastatic epidural spinal cord compression: current concepts and treatment.

Metastatic epidural spinal cord compression (MESCC) is a medical emergency complicating the course of 5-10% of patients with cancer [1]. When diagnosis and treatment is early with the patient ambulatory prognosis for continued ambulation is good [2]. If the patient is nonambulatory or paraplegic, prognosis for meaningful recovery of motor and bladder function is markedly decreased. In the last decade, significant advances in the understanding, management and treatment of metastatic epidural spinal cord compression have occurred. Recent pathophysiological and pharmacological animals studies have afforded insights into disease mechanisms [3-9]. The audit of standard methods of investigation and magnetic resonance imaging have resulted in revision of guidelines for patient evaluation [10-17]. Finally, new surgical philosophies and technical advances have generated interest and controversy [18-25]. With improved clinical awareness, new imaging modalities will help us diagnose epidural spinal cord compression earlier and institute appropriate treatment.

Animals↗