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Biomedical subjects

D G Thomas

Publications and source records attributed to D G Thomas.

At least 19 recordsLinked to original sources
PubMed2001

Gain of 1q and loss of 22 are the most common changes detected by comparative genomic hybridisation in paediatric ependymoma.

Ependymomas are the third most common brain tumour in the paediatric population. Although cytogenetic and molecular analyses have pinpointed deletions of chromosomes 6q, 17, and 22 in a subset of tumours, definitive patterns of genetic aberrations have not been determined. In the present study, we analysed 40 ependymomas from paediatric patients for genomic loss or gain using comparative genomic hybridisation (CGH). Eighteen of the tumours (45%) had no detectable regions of imbalance. In the remaining cases, the most common copy number aberrations were loss of 22 (25% of tumours) and gain of 1q (20%). Three regions of high copy number amplification were noted at 1q24-31 (three cases), 8q21-23 (two cases), and 9p (one case). Although there was no association with the loss or gain of any chromosome arm or with benign versus anaplastic histologic characteristics, the incidence of gain of 7q and 9p and loss of 17 and 22 was significantly higher in recurrent versus primary tumours. This study has identified a number of chromosomal regions that may contain candidate genes involved in the development of different subgroups of ependymoma.

Adolescent↗
PubMed2001

In-hospital mortality from abdominal aortic surgery in Great Britain and Ireland: Vascular Anaesthesia Society audit.

BACKGROUND: The mortality rate associated with elective aortic aneurysm repair is widely assumed to be in the region of 5 per cent. This figure does not take into consideration the effect of pre-existing risk factors. The Vascular Anaesthesia Society of Great Britain and Ireland conducted a large audit to estimate the in-hospital mortality rate associated with non-emergency infrarenal aortic surgery throughout the British Isles, and to determine the influence of risk factors on mortality rate. METHODS: This was a multicentre, prospective audit of 177 hospitals throughout the UK and Ireland. Data were collected by questionnaire to include all patients undergoing elective or urgent surgery for infrarenal abdominal aortic aneurysm or aortoiliac occlusive disease over 4 months. RESULTS: Nine hundred and thirty-three patients were recruited into the audit. The overall mortality rate was 7.3 per cent. Factors increasing the risk of death by up to fivefold included age over 74 years, urgent surgery, operation for occlusive disease, limited exercise capacity, a history of severe angina or cardiac failure, the presence of ventricular ectopics and abnormalities suggesting ischaemic heart disease on electrocardiography. CONCLUSION: Although the in-hospital mortality rate was similar to previously published figures, the rate increased considerably when commonly encountered risk factors were present.

Adult↗
PubMed2001

Interactive image-guided transcallosal microsurgery for anterior third ventricular cysts.

Although the treatment of colloid cysts remains controversial, high viscosity and small volume are poor prognostic indicators for successful burr hole aspiration and cortical incision via craniotomy may be associated with postoperative epilepsy. The anterior transcallosal approach provides a direct and adequate pathway to the lateral ventricles, where the foramen of Monro serves as a natural entrance into the anterior third ventricle, especially when the foramen is dilated by a lesion. When the midsuperior portion of the IIIrd ventricle cannot be reached, the interforniceal or the subchoroidal exposures have been advocated. Stereotactic techniques contribute to a minimal invasive approach and reduce morbidity. Nine patients harbouring anterior third ventricular cysts (seven colloids and two intrinsic craniopharyngiomas) underwent anterior transcallosal microsurgical excision assisted by an interactive infrared-based image guided system (EasyGuide, Neuro, Philips). There were 4 men and 5 women ranging in age from 15 to 42 years (mean 28.5). Transcallosal transforaminal (5 cases) or interforniceal (4 cases) approaches allowed total excision in eight patients and subtotal in one. Postoperative morbidity included a case of transient hemiparesis and a case of transient short-term memory disturbances; both resolved in the first months. Mortality was zero. Particular advantages of the method were accurate trajectory and position of callosotomy incision determination, visualisation and avoidance of superior saggital sinus, retraction of bridging veins and the often variable pericallosal arteries, spatial orientation within the ventricular system, and identification of the periventricular anatomical structures.

Adolescent↗
PubMed2001

Response of short-term cultures derived from human malignant glioma to aziridinylbenzoquinone, etoposide and doxorubicin: an in vitro phase II trial.

The relative resistance of malignant glioma to chemotherapy makes the identification of new cytotoxic drugs critically important. The use of short-term cultures derived from these tumors to screen drugs at doses that can be attained within human intracranial tumors provides a model system that should be capable of identifying effective drugs suitable for clinical evaluation. The sensitivity of a panel of short-term cultures derived from 22 malignant astrocytoma and four malignant oligodendroglioma was assessed to aziridinylbenzoquinone (AZQ), etoposide and doxorubicin (DOX) using a [(35)S] methione uptake assay. The ID(50) of each culture was compared to the levels of drug which could be achieved in the tumor using standard doses. There was marked heterogeneity between cultures in response to each drug. Whilst there was no evidence that cultures derived from grade III astrocytoma were more sensitive to any of the drugs than cultures derived from grade IV astrocytoma, cultures derived from oligodendroglioma tended to be more sensitive to the alkylating agent AZQ, but not to either of the other drugs. The sensitivity of these short-term cultures at concentrations that can be achieved in situ corresponded well with the clinical efficacy of AZQ and etoposide. Although DOX appeared to be toxic to human gliomas cells in vitro, its limited penetration into the intact brain would seem to preclude its use i.v., but it is likely to be effective if local drug delivery techniques could be employed. The study suggests that short-term cultures derived from malignant glioma should be used to screen investigational agents for potential clinical efficacy.

Antineoplastic Agents↗
PubMed2001

Clinical validation of true frameless stereotactic biopsy: analysis of the first 125 consecutive cases.

OBJECTIVE: A lockable guide device, adjustable for positioning, was used to obtain samples for tissue analysis during brain biopsy procedures performed using an interactive image guidance system. Clinical validation of this technique, which was developed for true frameless stereotactic biopsies, and analyses of the histological yield, complication rate, and patient demographic characteristics for a large series of frameless stereotactic biopsies were the purposes of this study. METHODS: Demographic, radiological, surgical, and clinical data were prospectively collected for a series of 125 frameless stereotactic biopsies performed using the technique described in detail previously. RESULTS: Eighty-six procedures were magnetic resonance imaging-directed and 39 were computed tomography-directed. The mean diameter of the biopsied lesions was 36 mm, and the mean distance from the skin was 35.8 mm. Sixteen percent of the patients harbored multiple lesions, and 5.6% of the biopsied lesions were infratentorial. The mean operative time (including the entire anesthetic time) was 1.5 hours. The smear examination findings were corroborated by conclusive histological results in 96% of the cases, and definitive positive diagnoses were obtained in 122 cases (97.6%). Ten patients experienced surgical complications, but the sustained morbidity rate was 2.4% (including the death of a patient who was in critical clinical condition preoperatively and who died 2 mo later as a result of a chest infection; mortality rate, 0.8%). CONCLUSION: This true frameless stereotactic biopsy technique was associated with low morbidity and mortality rates and an excellent diagnostic yield, with overall results at least as good as those observed for frame-based stereotaxy. The excellent accuracy results demonstrated previously and statistically significant reductions in operative time, as well as improved image presentation, target selection, and simplicity, support the use of this frameless stereotactic technique in preference to frame-based biopsy techniques.

Adult↗
PubMed2000

Firing patterns of pallidal cells in parkinsonian patients correlate with their pre-pallidotomy clinical scores.

It is unclear how the disordered activity of cells in the basal ganglia contributes to the symptoms of Parkinson's disease (PD). We recorded from single neurons extracellularly in 3 regions of the globus pallidus (GPe, GPie and GPii) in patients undergoing pallidotomy for PD. Movement-related cell firing patterns, analysed using hidden Markov models, were significantly correlated with patients' preoperative clinical scores (off drugs). Responses of cells in GPii correlated best with the scores for specific motor tasks, rather than general ones related to activities of daily living, but the reverse was true for responses from GPe. In both GPii and GPe, a higher score (i.e. greater parkinsonian severity) was associated with greater variability in cell firing rather than an increase in firing rate itself.

Activities of Daily Living↗
PubMed2000

Benign central neurocytoma.

BACKGROUND: "Central neurocytoma" is classically considered as an intraventricular benign tumor, largely based on data from small retrospective series. The authors present prospective data on 12 patients with tumors diagnosed as central neurocytoma, to highlight the diverse nature of this tumor and challenge the classic notion. METHODS: Between 1991 and 1997, 12 patients had tumors diagnosed prospectively as "central neurocytoma". Clinical, radiologic, and histologic data were collected, and Karnofsky performance score was evaluated for each patient. Proliferation marker studies were performed using Ki-67 labeling index. RESULTS: In two patients, the tumors were located in atypical locations, namely, the parietal lobe and the spine. Aggressive behavior characterized by clinical and radiologic evidence of tumor progression was noted in two additional patients. In both these cases, unusually high proliferation rates of 5.3% and 11.2% were noted. Total excision of the tumor, when possible, was the treatment of choice. Postoperative radiotherapy to the residual tumor may be of benefit in patients with clinically aggressive tumors, or those with high proliferation rates. CONCLUSIONS: Given the findings of this study, it is suggested that the traditional concept of central neurocytoma as a benign intraventricular tumor warrants reconsideration.

Adolescent↗
PubMed2000

Chemosensitivity in childhood brain tumours in vitro: evidence of differential sensitivity to lomustine (CCNU) and vincristine.

The aim of this study was to examine the range of sensitivity of a panel of short-term cultures derived from different types of malignant childhood brain tumours including medulloblastoma, ependymoma and glioblastoma multiforme to three cytotoxic drugs, lomustine (CCNU), vincristine (VCR) and procarbazine (PCB). Sensitivity was assessed using a modification of the dimethylthiazolyl-2,5-diphenyl tetrazolium bromide (MTT) assay. Short-term cell lines derived from ependymomas were considerably more resistant to VCR than other types of childhood brain tumours, while cultures derived from supratentorial primitive neuroectodermal tumour (PNET) displayed marked sensitivity to both lomustine and VCR. Cultures from ependymomas, medulloblastoma and astrocytic gliomas had similar sensitivity to lomustine and PCB as cultures derived from adult malignant astrocytoma.

Adult↗
PubMed2000

Spinal neurenteric cysts without associated malformations. Are they the same as those presenting in spinal dysraphism?

Spinal neurenteric cysts are rare intradural developmental lesions, usually composed of a thin-walled cyst whose lining mimicks gastro-intestinal or respiratory epithelium. A detailed review of the literature revealed 80 cases of solitary spinal neurenteric cysts (including a new case of ours), which were analysed and compared, regarding clinical and pathological aspects, with 56 such cases of those with concomitant evidence of dysraphism. Older age and cervical location were found to be statistically characteristic of the solitary cysts in contrast to younger age and lumbosarcal location for the 'dysraphic' cases. Magnetic resonance imaging is the diagnostic modality of choice. Good evidence of the developmental origin of incomplete separation of notochord and endoderm was given by the fact that histologically solitary cysts were mainly composed by endodermal derivatives, while 'dysraphic' had also mesenchymal and ectodermal elements. Thus, it seems that additional spinal dysraphic changes are more likely to be found when ectodermal and mesenchymal elements co-exist with endodermal ones, possibly indicating an earlier error in development than in other cases containing only endodermal elements.

Humans↗
PubMed2000

Intracerebral haemorrhage and drug abuse in young adults.

The epidemic of abuse of the so-called 'designer drugs' amphetamine, cocaine and ecstasy--is fast replacing traditional aetiological factors as the largest cause of intracerebral haemorrhage among young adults. Traditional teaching is that these represent hypertensive haemorrhages. Recent reports, however, have indicated that these patients may harbour underlying vascular malformations. We review 13 patients with a positive history of drug abuse preceding the onset of intracerebral haemorrhage. These patients presented to the National Hospital for Neurology and Neurosurgery in central London over a 7-month period. Of the 13 patients (eight male, five female), average age 31 years (19-43) years), 10 were well enough to undergo cerebral angiography. Intracranial aneurysms were demonstrated in six patients and arteriovenous malformations in three patients. In only one of the patients was the angiogram normal. A further patient was subsequently shown to have a middle cerebral artery aneurysm at autopsy. The epidemiology, pharmacology and systemic effects of these drugs are considered. The mechanisms by which these compounds cause intracerebral complications and their influence on prognosis are discussed. The incidence of intracerebral haemorrhage (ICH), ischaemic cerebral infarctions and subarachnoid haemorrhage (SAH) following drug abuse is increasing. Contrary to historical opinion, drug-related ICH is frequently related to an underlying vascular malformation. Arteriography should be part of the evaluation of most young patients with nontraumatic ICH. A thorough history focusing on the use of illicit substances and toxicological screening of urine and serum should be part of the evaluation of any young patient with a stroke.

Adult↗
PubMed2000

Scintillation autofluorographic assessment of isotope uptake in human glioma cells grown on microtitration plates using sodium salicylate.

We describe a simple method for detecting [35S]methionine-labeled protein in fixed human astrocytoma cells grown in 96-well microtitration plates using a modified scintillation autofluorographic method. Following isotopic labeling, cells are fixed in situ and a solution of salicylic acid in methanol is dried onto the cell layer. The fluorographic image is detected using blue-sensitive X-ray film attached to the base of the plate which, following development, can be quantitated using a scanning densitometer. The relationship between cell number and optical density is linear, and there is a close correlation between the dose-response curves generated by this method and alternative isotopic detection methods and cell counting. This assay provides a suitable alternative to the use of potentially toxic scintillation fluids based on organic solvents like toluene or xylene in chemosensitivity testing of human brain tumors.

Brain Neoplasms↗
PubMed2000

Clinical utility and cost-effectiveness of interactive image-guided craniotomy: clinical comparison between conventional and image-guided meningioma surgery.

OBJECTIVE: Although interactive image guidance has been determined to be an increasingly important and reliable tool in contemporary neurosurgery, the clinical results and cost-effectiveness of the use of these systems, compared with conventional techniques, remain understudied. The aim of this study was to investigate the possible benefits of image-guided craniotomies to treat meningiomas, in terms of hospital stays, surgical complications, and, consequently, cost-effectiveness, compared with the results of standard surgery (SS). METHODS: During a 3.5-year period, 100 patients were surgically treated for meningiomas using image-guided surgery (IGS) with neuronavigation assistance and 170 were surgically treated using SS. From the consecutive series of the 100 IGS cases, it was possible to statistically match 50 (in terms of the demographic data, the location and size of the tumor, and the experience of the surgeon) with 50 SS cases. The clinical data were collected prospectively for the IGS group and retrospectively for the SS group. RESULTS: The anesthetic (operation) times were similar for the two groups, although surgical times were shorter for the IGS group (P = 0.02). Blood loss during surgery was less for the IGS group (although not statistically significantly, P > 0.05), but more SS cases required transfusions (P = 0.03). The mean intensive therapy unit stay was 1.7 days for the SS group and 1 day for the IGS group (P = 0.12); the mean hospital stays were 13.5 and 8.5 days, respectively (P = 0.017). Severe complications (permanent or requiring additional surgical procedures) were encountered in 14% of the cases in the SS group and 6% of the cases in the IGS group (P = 0.019), whereas the rates of minor complications (resolved within 30 d without further surgery) were similar (8 and 10%, respectively). The most common problems for the control group were postoperative hematomas (n = 3), which required urgent surgery in two cases; intractable postoperative swelling was treated by lobectomy in another case. In the IGS group, the two severe complications included one case of an infected bone flap and one case of a new permanent neurological deficit. The mean cost per patient was approximately 20% higher for SS than for IGS. CONCLUSION: Although this was not a randomized study, the analysis of these results strongly suggests a positive effect of neuronavigation on the complication rate and thus on intensive care unit and hospital stays, with attendant financial implications.

Adult↗
PubMed2000

Stereotactic conformal radiotherapy for pituitary adenomas: technique and preliminary experience.

OBJECTIVE: Stereotactic conformal radiotherapy (SCRT) is a high precision technique of fractionated radiotherapy which ensures accurate delivery of radiation with reduction in the volume of normal tissue irradiated as compared to conventional external beam radiotherapy. We describe the technique and preliminary experience of SCRT in patients with residual and recurrent pituitary adenomas. PATIENTS AND METHODS: Between February 1995 and March 1999, 22 patients (mean age: 45.3, range: 20-67 years) with residual or recurrent pituitary adenomas (13 nonfunctioning, nine secretory) were treated with SCRT. All were immobilized in a relocatable Gill-Thomas-Cosman (GTC) frame and tumour was localized on a postcontrast planning computerized tomography (CT) and MRI scan. The gross tumour volume (GTV) and the critical structures were outlined on contiguous 2-3 mm separated slices. A margin of 5 mm (12 patients) to 10 mm (10 patients) was grown around GTV in three-dimensions (3-D) to generate the planning target volume (PTV). The treatment was delivered by three (five patients) and four (17 patients) maximally separated conformal fixed fields with each field conformed to the shape of the tumour using customized lead alloy blocks (19 patients) or multileaf collimator (three patients). The patients were treated on a 6-MV linear accelerator to a dose of 45 Gy in 25 fractions (18 patients) and 50 Gy in 30 fractions (four patients). RESULTS: The technique of SCRT has become a part of the routine work of the radiotherapy department. The treatment was well tolerated with minimal acute toxicity. One patient developed transient quadrantanopia 2 weeks after treatment with full recovery after a short course of corticosteroids. One patient had a transient visual deterioration 7 months after treatment due to cystic degeneration of the tumour which fully recovered following surgical decompression. Nine of the 15 patients presenting with visual impairment had improvement after treatment and the visual status remained stable in all others. One patient with acromegaly and one with a prolactinoma achieved normalization of elevated hormonal abnormality four and 10 months after SCRT, respectively. The remaining seven patients with a secretory adenoma had declining hormone levels at last follow-up. Newly initiated hormone replacement therapy was required in five patients. At a median follow-up of 9 months (range 1-44 months), the 1 and 2 year actuarial progression free and overall survival were 100%. CONCLUSION: Stereotactic conformal radiotherapy is a high precision technique suitable for the treatment of pituitary adenomas requiring radiotherapy. Preliminary results suggest effective tumour control and low toxicity within the range expected for conventional external beam radiotherapy. While the technique is of potential benefit in reducing the volume of normal brain irradiated, the advantages in terms of sustained tumour control and reduced toxicity over conventional radiotherapy need to be demonstrated in long-term prospective studies.

Adenoma↗
PubMed2000

The impact of stimulus 'value' in infant novelty preference.

Various factors have been identified that influence the robust phenomenon of novelty preference in infants. The present study consisted of two experiments that investigated whether conditioned 'value' is another variable that influences infants' preferences. In Experiment 1, novelty preference was established to simple tones despite the tones differing only in frequency. In Experiment 2, novelty preference was manipulated by pairing a primary reinforcer with the familiarization tone such that the conditioned value overrode novelty preference. The findings raise questions about the universality of predicting infants' preferences solely on the foundation of amount of stimulus experience.

Acoustic Stimulation↗
PubMed1999

Structural changes induced by mupirocin in Staphylococcus aureus cells.

Cells of mupirocin-sensitive, moderately-resistant and highly-resistant cultures of Staphylococcus aureus (mupirocin MICs 0.13, 16 and > 512 mg/l, respectively) were exposed to various concentrations of the antibiotic and examined by transmission electron microscopy. The most severe damage occurred in mupirocin-sensitive cells. Cells from moderately-resistant cultures trained in vitro to high-level mupirocin resistance were more hydrophobic than the parent cells. The antibiotic was slowly lethal to the mupirocin-sensitive strain and sub-inhibitory concentrations prevented or reduced growth of the other strains over a 6 h incubation period, irrespective of whether the drug was added at zero time or in the exponential growth phase.

Anti-Bacterial Agents↗
PubMed1999

Mupirocin resistance in staphylococci: development and transfer of isoleucyl-tRNA synthetase-mediated resistance in vitro.

Mupirocin resistance could be transferred from highly resistant clinical isolates of Staphylococcus aureus to highly sensitive recipients of Staph. aureus, Staph. epidermidis and Staph. haemolyticus. Transconjugants of the latter two organisms could transfer this resistance into mupirocin-sensitive Staph. aureus. Moderately resistant strains did not transfer this resistance to sensitive recipients, nor did strains with high-level mupirocin resistance developed by serial transfer or habituation. The inhibitory effects of mupirocin on crude isoleucyl-tRNA synthetases (IRS) isolated from mupirocin-sensitive and -resistant strains of Staph. aureus have been determined. Drug concentrations needed to produce 50% inhibition, I50 values, were very low against IRS from a highly sensitive strain, somewhat higher against IRS from moderately resistant strains, much higher against enzyme from strains trained in vitro to high-level resistance, and considerably higher still against IRS extracted from clinical isolates possessing high-level mupirocin resistance and from the transconjugates of such strains resulting from crosses with mupirocin-sensitive strains. It is concluded that high-level resistance in clinical isolates is plasmid-mediated involving a second, mupirocin-resistant IRS whereas in moderately resistant strains, and in strains trained in vitro to high-level resistance, chromosomal mutations are likely to be responsible for decreasing IRS sensitivity.

Anti-Bacterial Agents↗
PubMed1999

MRI-guided stereotactic brain biopsy: a review of 33 cases.

MRI is being increasingly used for the detection of intracranial lesions. MRI-guided stereotactic brain biopsy is infrequently performed. We audited our recent experience of this procedure, and demonstrated that it is feasible and comparable to CT-guided biopsy in terms of diagnostic accuracy with a low procedural morbidity. We critically analyse its future role in the presence of more recent developments.

Adult↗