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Biomedical subjects

D G Thomas

Publications and source records attributed to D G Thomas.

At least 145 records · Page 8Linked to original sources

Does combined epidural lignocaine and fentanyl provide better anaesthesia for ESWL than lignocaine alone?

The efficacy of epidural fentanyl combined with lignocaine 1.5% with adrenaline 1:200,000 was studied in a randomised, double-blind, controlled trial of two hundred patients undergoing extracorporeal shock wave lithotripsy with or without ancillary procedures. The quality of anaesthesia was assessed using linear analogue pain scores, the patient's impression, and the rate of intra-operative intervention by the anaesthetist. Postoperative symptomatology was also recorded. The only significant difference lay postoperatively in that the fentanyl-ancillary procedure sub-group had less pain approximately one hour postoperatively (P = 0.01). In the context of this study and in the presence of an adequate autonomic and somatic local anaesthetic blockade, the addition of epidural fentanyl does not appear to confer any significant advantage other than to enhance postoperative analgesia.

Anesthesia, Epidural↗

The initial experience with the Cosman-Roberts-Wells stereotactic system.

The Cosman-Roberts-Wells stereotactic instrument is a recently developed modification, based on an arc-radius design, of the Brown-Roberts-Wells stereotactic frame utilizing the existing fixation and fiducial components of the Brown-Roberts-Wells stereotactic system to localize and verify target data. The design modification has been made with a view to facilitating technical approaches both in stereotactic biopsy and in stereotactic craniotomy, whilst encompassing the same stereotactic space. Initial experience with the Cosman-Roberts-Wells instrument is reported. Over a 5-month period 55 procedures were performed which included 40 stereotactic biopsies, five CT-guided stereotactic craniotomies, three stereotactic placements of a Bennett Ball for thalamotomy, three stereotactic implantations of intracranial electrodes for recording in drug-resistant epilepsy, three aspirations of cyst or haematoma and one implantation of a Gutin catheter for interstitial brachytherapy. There was minimal morbidity and no mortality related to operation. This frame offers rapid targeting without the need to pre-determine entry points, as well as allowing direct lateral passes and unimpeded stereotactic craniotomy.

Adolescent↗

Stereotactic biopsy of cerebral lesions in patients with AIDS.

Central nervous system involvement with AIDS is not uncommon. The indications and timing of brain biopsy remains controversial. Stereotactic CT-guided biopsy offers a safe and effective means of establishing a diagnosis in any patient with a cerebral mass lesion and has less morbidity and mortality than freehand biopsy or exploratory craniotomy. Eleven patients with AIDS have undergone CT-directed stereotactic biopsy between May 1987 and November 1990 with one death from intracerebral haemorrhage. Histological diagnosis of the biopsy specimens showed multifocal leucoencephalopathy, toxoplasmosis, lymphoma and non-specific changes. Biopsy is recommended for patients with an atypical presentation, negative serology, progressive clinical deterioration and differential response of lesions to empirical therapy.

AIDS Dementia Complex↗

Multicentric malignant glioma.

Multicentre gliomas are a well recognized entity but the occurrence of such tumours both above and below the tentorium remains uncommon. We report the case of an 11-year-old boy who underwent stereotactic biopsy of a brain stem ring enhancing tumour with histology of an anaplastic astrocytoma (Grade 3). Nine months following his radiotherapy a large left frontal mass was biopsied and found to be a malignant glioma (Grade 4). Advances in neuroradiological imaging will readily show multiple cerebral lesions and multicentre glioma should be considered in the differential diagnosis of such lesions and biopsy is indicated.

Astrocytoma↗

Cell proliferation in serial biopsies through human malignant brain tumours: measurement using Ki67 antibody labelling.

Cell proliferation was assessed in brain tumours using the monoclonal antibody Ki67 which recognizes a nuclear antigen expressed by proliferating cells. Using a novel stereotactic biopsy procedure, serial 1 cm biopsies were taken along a trajectory through six malignant brain tumours. Specimens were also obtained from 10 other brain tumours during conventional surgery. The percentage of Ki67 positive cells was determined as a fraction of the total number of tumour cells present. The Ki67 index for anaplastic astrocytomas and glioblastomas was significantly higher (Ki67 index range 11-18%) than that for benign or low grade tumours. Significant variation in proliferation was measured along the biopsy track through individual tumours (e.g. 0-12.3%) which correlated well with histological appearance. The Ki67 indices of normal brain were very low. In general the Ki67 indices increased with increasing histological grade and also appear to be a useful indicator of the active tumour volume and margin. This method provides spatial information about tumour proliferation which may be used to decide between different treatments and relate to prognosis.

Adult↗

Retinoblastoma gene deletions in human glioblastomas.

The retinoblastoma susceptibility gene, RB, is the best characterised of the tumour suppressor genes, or 'anti-oncogenes'. Abnormal function of the RB protein is thought to result in loss of an inhibitory effect on cell growth, and thus contribute towards the development of certain human cancers. One group of human cancers of particular interest in relationship to retinoblastoma gene function are the gliomas, which are central nervous system tumours thought to originate from the neuroectoderm, the embryological tissue which also gives rise to retinoblastomas. We have therefore examined a group of benign and malignant gliomas for evidence of structural alterations of the RB gene. Four out of nine (44%) glioblastomas, the most malignant gliomas, showed loss of heterozygosity of a locus within this gene. In addition, one of these hemizygous tumours showed deletion of part of the RB protein-coding region, and this abnormality was also present in cells cultured from the tumour. These findings suggest that RB gene abnormalities may contribute to the development of glioblastomas.

Alleles↗

The VM model of glioma: preparation of multicellular tumour spheroids (MTS) and their response to chemotherapy.

A cell line, 497-P(1), derived from the VM spontaneous murine astrocytoma has been used to develop an in vitro therapeutic model of human glioma. In this study we describe the preparation of MTS from this cell line. The in vitro chemosensitivity of 497-P(1) MTS has been examined and compared to the sensitivity of the monolayer culture. BCNU and CCNU both produced growth delay in MTS at doses below the ID50 of the monolayer culture. MTS, however, were considerably more resistant to vincristine and procarbazine when compared to the monolayer culture.

Animals↗

The chemotherapeutic response of a murine (VM) model of human glioma.

Using a cell line derived from the VM spontaneous murine astrocytoma, a reliable in vitro-in vivo model of human malignant glioma has been developed. In this paper we examine the effects of cytotoxic drugs with known activity against other animal brain tumour models and human disease on the in vivo VM model. The drugs BCNU, CCNU and vincristine produced significant volume reduction in tumours growing at a subcutaneous location in syngeneic animals. Procarbazine was ineffective. Similarly, BCNU, CCNU and vincristine produced small but statistically significant increases in survival of VM mice bearing the intracerebral tumour, but procarbazine was again ineffective. The modest, but significant, response of the VM model to the nitrosoureas mimics the human situation more closely than previously described animal models.

Animals↗

Urinary continence in spinal injury patients following complete sacral posterior rhizotomy.

Complete sacral posterior rhizotomy was carried out in 15 spinal injury patients in conjunction with implantation of sacral anterior root stimulators. All patients were incontinent pre-operatively and had video-pressure cystometry before and at regular intervals after surgery. Detrusor hyper-reflexia was totally abolished in all but 1 patient following rhizotomy and 87% no longer require any form of incontinence appliance. Deafferentation produced adverse changes in vesicourethral function and even when rhizotomy was complete, continence could not be guaranteed. The pre-operative state of the bladder neck and distal sphincter mechanism had an important bearing on future continence and those patients with a closed bladder neck and no previous sphincterotomy had the greatest chance of becoming continent after deafferentation. The majority of patients in this series are now fully continent, representing a transformation in their quality of life; it is recommended, however, that to optimise the success of rhizotomy precise pre-operative evaluation and selection of patients are essential.

Adult↗

Lumbosacral evoked potentials and vesicourethral function in patients with chronic suprasacral spinal cord injury.

Persistent detrusor acontractility despite normal somatic reflex activity in some patients with high spinal cord injury is an enigma. Previous work has suggested disordered integration of afferent activity in sacral roots or the sacral spinal cord. Forty male patients with chronic stable suprasacral cord lesions were studied by filling and voiding videocystometrography, and recording lumbosacral evoked potentials from posterior tibial nerve stimulation. Only five of 15 patients with decreased detrusor contractility had abnormal lumbosacral evoked potentials. Similar abnormalities were found in four of 11 patients with efficient hyperreflexic bladders. The finding of normal lumbosacral evoked potentials in the majority of patients with suprasacral cord injuries and decreased detrusor contractility supports the argument that the pathophysiology of this specific form of neurogenic bladder dysfunction is multifactorial.

Adolescent↗

Use of relocatable stereotactic frame to integrate positron emission tomography and computed tomography images: application in human malignant brain tumours.

A stereotactic head frame has been developed which is accurately relocatable over an extended period of time, is non-invasive, and yet is rigidly fixed relative to the patient's skull. Eight patients with malignant brain tumours were studied by positron emission tomography scanning using 18FUDR and computed tomography scan. Serial biopsies were performed and were studied by routine histological methods and using the monoclonal antibody Ki67.

Antigens, Surface↗

Brain metabolites as 1H NMR markers of neuronal and glial disorders.

1H NMR spectroscopy of human brain in vivo can be used to detect a number of cerebral metabolites including N-acetylaspartate, creatine + phosphocreatine and choline-containing compounds. We have used 1H NMR spectroscopy to analyse these signals in (i) biopsy material from both normal human brain and astrocytomas, and (ii) primary astrocyte cultures. On the basis of this analysis, we conclude that in vivo 1H NMR spectroscopy could play an important clinical role in the non-invasive assessment of neuronal degeneration and proliferation of non-neuronal cells.

Animals↗

Lack of relationship of conus reflexes to bladder function after spinal cord injury.

A series of 20 patients with acute complete suprasacral cord lesions underwent serial urodynamic assessment of vesicourethral function and serial measurement of sacral reflex latency times (SRL) and reflex threshold throughout a follow-up period of 42 to 83 weeks (mean 50). No correlation was found between any pattern of SRL latencies or reflex thresholds and subsequent bladder behaviour. The reproducibility of sacral reflex latencies was found to be poor (mean variation of serial measurements from initial reading 21%) and could not be explained on the basis of "dynamic" neurological recovery. Studies using the bladder as a stimulus site were unreliable. The value of SRL studies in detecting subtle neurophysiological changes is discussed.

Adolescent↗

The development of an animal model of glioma for use in experimental neuro-oncology.

A cell line, 497-P(1), derived from the VM spontaneous murine astrocytoma has been used to develop an in vitro in vivo model of human glioma. This paper describes the growth characteristics of tumours produced after intracerebral or subcutaneous inoculation of 497-P(1) cells into syngeneic VM mice. The results show that cell line 497-P(1) provides the basis for a reproducible animal model of glioma which fulfils many of the criteria required for experimental therapy studies.

Animals↗

Experience in 300 cases of CT-directed stereotactic surgery for lesion biopsy and aspiration of haematoma.

Despite advances in imaging of the brain, an accurate diagnosis of brain lesions requires tissue sampling and histological verification. A series of CT-directed procedures has been performed in 300 patients with deep sited, multiple, diffuse, extensive, small or inflammatory lesions, brain stem haematomas and tumours presenting with epilepsy. A positive diagnosis was obtained in 271 cases (92.8%), no diagnosis in 21 cases (7.2%). Therapeutic results were also obtained in eight cases (2.7%) of brain stem haematoma aspiration. Complications occurred in 14 cases (4.7%) including one death (0.3%). Because of the importance of an accurate diagnosis in order to avoid inappropriate therapy, together with the relative safety of the technique, CT-directed stereotactic biopsy should be considered in all patients harbouring deep seated, multiple, diffuse, small or inflammatory brain lesions.

Adolescent↗