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Biomedical subjects

D G Thomas

Publications and source records attributed to D G Thomas.

At least 37 records · Page 2Linked to original sources
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

Routes and doses of lignocaine hydrochloride for analgesia of the velvet antler of stags.

AIM: To evaluate the effectiveness of various routes of administration and doses of local anaesthetic to provide analgesia of the velvet antler of young stags. METHODS: In study 1, in which an electrical stimulus was used, 64 l-year-old male red and red X wapiti deer with velvet antler lo-30 cm long, were randomly allocated to one of ten treatments with four treatments/animal, and 23 or 24 antlers/treatment. Treatments delivered included three control groups, three local anaesthetic (2% lignocaine HCL) doses delivered by ring block (5, 10 or 15 ml per pedicle), and a high or low regional block with or without an auriculopalpebral nerve block (5 ml per site). An electrical stimulus was applied before and 1,2,4 and 8 minutes after local anaesthetic treatments and to controls, at an increasing voltage until a response was observed. The voltage and animal responses were recorded. In Study 2 the same seven local anaesthetic treatments (16-I 8 antlers/treatment) were evaluated using 58 of the stags from Study 1 when antlers were ready for removal, but a saw cut was used as the test stimulus. A test cut was applied to the antler I,2 and 4 minutes after application of local anaesthetic. If no response was observed, the antler was removed at that time. RESULTS: In Study 1, major dose and treatment effects were significantly different (p < 0.05) with the outcome variable being whether or not the deer responded. No stags given the high dose ring block responded to electrical stimulation 1 minute after treatment, one responded at 2 minutes, and none responded at 4 or 8 minutes. At least one animal responded after all other treatments at all time intervals. More deer responded after the low regional block than the high regional block, and there was a lower response rate when the auriculopalpebral nerves were anaesthetised. In Study 2, no deer responded 2 minutes after the medium dose ring block treatment. Three of 18 stags receiving the high dose ring block still responded after 2 minutes, and one responded after 4 minutes. Responses occurred to all other treatments at each time, with some deer requiring further administration of local anaesthetic before antler removal, even with the four minute waiting period. CONCLUSION: Ring blocks produced more consistent analgesia of the velvet antler than regional nerve blocks. The high dose ring block produced analgesia faster and more effectively than lower doses, and the regional nerve blocks were more effective when the auriculopalpebral nerve was blocked.

Journal Article↗
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↗
PubMed1999

Sensitivity of short-term cultures derived from human malignant glioma to the anti-cancer drug temozolomide.

The activity of temozolomide, which has shown clinical activity against malignant glioma, has been assessed in vitro against short-term cultures derived from these tumors using an intermediate duration microtitration assay with MTT reduction as the end-point This assay has previously been shown to correlate closely with a monolayer clonogenic assay. Sensitivity was assessed in 15 short-term cultures (passage levels 3-9) derived from WHO grade III and IV astrocytomas. These cultures had a median ID50 value of 258 microM for temozolomide and 16.13 microM for CCNU. Maximum serum concentrations of temozolomide are of the order of 75 microM but only three of 15 (20%) cultures had ID50s below this value. Fourteen of 15 (93%) cultures displayed cross-resistance between temozolomide and CCNU, although one line which was extremely resistant to CCNU retained sensitivity to temozolomide. Comparative studies of published clonogenic survival curves indicate that the short-term glioma cell lines used in this study have similar sensitivities to established glioma cell lines, whilst colon carcinoma cell lines and bladder carcinoma are often more resistant to these drugs. Cell lines from testicular teratoma cell lines may show exquisite sensitivity to temozolomide and this level of sensitivity is seen only occasionally in short-term cultures derived from malignant glioma.

Adult↗
PubMed1999

Does P-glycoprotein play a role in clinical resistance of malignant astrocytoma?

P-glycoprotein (P-gp) is a 170 kDa transmembrane glycoprotein which plays a significant role in modulating pleomorphic or multiple drug resistance (MDR) in a wide variety of human cancers like renal and colorectal carcinoma. However, its role in modulating drug resistance in other types of cancer is less well defined. The purpose of this review is to critically examine the evidence that P-gp plays an important role in producing drug resistance in astrocytic gliomas. Malignant astrocytoma is clinically resistant to most types of cytotoxic drugs, including those associated with the MDR phenotype and the cross-resistance patterns of short-term cultures derived from malignant glioma are consistent with this phenotype. Consequently, it might be expected that this tumor would express high levels of P-gp. However, immunohistochemical findings from a number of previous studies have provided conflicting data about the expression of P-gp in these tumors, although P-gp has been consistently detected in normal brain in the endothelial cells in cerebral blood vessels and is thought to contribute to the blood-brain barrier phenomena. In order to determine if P-gp contributes to drug resistance in malignant astrocytoma, we undertook a study of P-gp expression in a panel of short-term cultures derived from these tumors in which we determined the in vitro chemosensitivity. However, immunocytochemical studies with a panel of antibodies which recognize both internal and external epitopes of the P-gp molecule have consistently failed to show the characteristic membrane staining associated with MDR in any of the cultures, including those markedly cross-resistant to vincristine and doxorubicin. One antibody, JSB-1, showed heterogeneous granular cytoplasmic staining which was unrelated to a particular pattern of drug resistance. This is probably because this antibody cross-reacts with a widely distributed cytoplasmic antigen, pyruvate carboxylase, which is present in abundance in normal astrocytes. The unexpectedly poor specificities of many of the antibodies thought to be specific for P-gp is reviewed in the context of malignant astrocytoma. In conclusion, the role of P-gp in producing drug resistance in malignant astrocytoma is questionable and further studies might more profitably concentrate on the mechanisms of resistance to DNA-damaging agents like the nitrosoureas, methylating agents or platinum-based drugs.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1999

Measurement of changes in opioid receptor binding in vivo during trigeminal neuralgic pain using [11C] diprenorphine and positron emission tomography.

The binding of [11C]diprenorphine to mu, kappa, and delta subsites in cortical and subcortical structures was measured by positron emission tomography in vivo in six patients before and after surgical relief of trigeminal neuralgia pain. The volume of distribution of [11C]diprenorphine binding was significantly increased after thermocoagulation of the relevant trigeminal division in the following areas: prefrontal, insular, perigenual, mid-cingulate and inferior parietal cortices, basal ganglia, and thalamus bilaterally. In addition to the pain relief associated with the surgical procedure, there also was an improvement in anxiety and depression scores. In the context of other studies, these changes in binding most likely resulted from the change in the pain state. The results suggest an increased occupancy by endogenous opioid peptides during trigeminal pain but cannot exclude coexistent down-regulation of binding sites.

Aged↗
PubMed1999

Unilateral pallidotomy for Parkinson's disease: results after more than 1 year.

OBJECTIVE: To examine follow up results of unilateral ventral medial pallidotomy in 22 patients with advanced Parkinson's disease more than 1 year after the operation in comparison with their results (previously reported) at 3 months. METHODS: Twenty patients who had undergone unilateral pallidotomy were assessed with the core assessment programme for intracerebral transplantation (CAPIT) protocol preoperatively, at 3 months postoperatively, and again after a median postoperative follow up of 14 months. Two further patients had only one evaluation 3 months postoperatively. RESULTS: The reduction of contralateral dyskinesias (median 67%) at 3 months was slightly attenuated after 1 year to 55% (both p<0.001 compared with baseline). A less pronounced effect on ipsilateral and axial dyskinesias decreased from 39% to 33% (p<0.005 and p<0.01), and from 50% to 12.5% (p<0.001 and p<0.01), respectively. However, there was no significant change between the 3 month and the follow up assessment. The modest improvement of the contralateral unified Parkinson's disease rating scale (UPDRS) motor score in the "off" state remained improved compared with preoperative levels, but less significantly (26%, p<0.001, and 18%, p<0.01). The activities of daily living (ADL) subscore of the UPDRS in the off state remained improved with median changes of 23% and 22% at follow up (both p<0. 005). There was no significant improvement of "on" state or ipsilateral off state motor scores. Median modified Hoehn and Yahr scores in off and on state were unchanged, as was the time spent off. Speech in off had significantly deteriorated by 1 year after the operation. CONCLUSIONS: The beneficial effects of unilateral pallidotomy persist for at least 12 months and, dyskinesias are most responsive to this procedure.

Adult↗
PubMed1999

Accuracy of true frameless stereotaxy: in vivo measurement and laboratory phantom studies. Technical note.

The authors present the results of accuracy measurements, obtained in both laboratory phantom studies and an in vivo assessment, for a technique of frameless stereotaxy. An instrument holder was developed to facilitate stereotactic guidance and enable introduction of frameless methods to traditional frame-based procedures. The accuracy of frameless stereotaxy was assessed for images acquired using 0.5-tesla or 1.5-tesla magnetic resonance (MR) imaging or 2-mm axial, 3-mm axial, or 3-mm helical computerized tomography (CT) scanning. A clinical series is reported in which biopsy samples were obtained using a frameless stereotactic procedure, and the accuracy of these procedures was assessed using postoperative MR images and image fusion. The overall mean error of phantom frameless stereotaxy was found to be 1.3 mm (standard deviation [SD] 0.6 mm). The mean error for CT-directed frameless stereotaxy was 1.1 mm (SD 0.5 mm) and that for MR image-directed procedures was 1.4 mm (SD 0.7 mm). The CT-guided frameless stereotaxy was significantly more accurate than MR image-directed stereotaxy (p = 0.0001). In addition, 2-mm axial CT-guided stereotaxy was significantly more accurate than 3-mm axial CT-guided stereotaxy (p = 0.025). In the clinical series of 21 frameless stereotactically obtained biopsies, all specimens yielded the appropriate diagnosis and no complications ensued. Early postoperative MR images were obtained in 16 of these cases and displacement of the biopsy site from the intraoperative target was determined by fusion of pre- and postoperative image data sets. The mean in vivo linear error of frameless stereotactic biopsy sampling was 2.3 mm (SD 1.9 mm). The mean in vivo Euclidean error was 4.8 mm (SD 2 mm). The implications of these accuracy measurements and of error in stereotaxy are discussed.

Adult↗
PubMed1999

Radiotherapy in the treatment of benign meningioma of the skull base.

OBJECT: This study was undertaken to assess the long-term efficacy and toxicity of conventional fractionated external-beam radiation in the treatment of benign skull base meningioma. METHODS: This is a retrospective study of 82 patients with histologically verified benign skull base meningioma treated by surgery followed by fractionated external-beam radiation at the Royal Marsden Hospital between 1962 and 1992. The 5- and 10-year progression-free survival (PFS) rates were 92% and 83%, respectively, with the site of disease being the only independent prognostic factor for tumor control according to multivariate analysis. The 10-year PFS rate for patients with sphenoid ridge meningiomas was 69% compared with 90% for those with tumors in the parasellar region. The overall 10-year survival rate was 71%, with performance status and patient age found to be significant independent prognostic factors. Six patients had worsening vision, which was due to cataract in five cases and retinopathy in one. There were no recorded cases of cranial nerve neuropathy. CONCLUSIONS: The excellent long-term tumor control and length of survival with minimal toxicity associated with conventional external-beam radiation should serve as a baseline for evaluation of new treatment strategies such as radiosurgery and skull base surgery.

Adolescent↗