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M Thomas

Publications and source records attributed to M Thomas.

At least 91 records · Page 5Linked to original sources
PubMed2004

Minocycline: neuroprotective mechanisms in Parkinson's disease.

Parkinson's disease (PD) is a common neurodegenerative disorder characterized by cardinal features of tremor, bradykinesia, rigidity and postural instability. In addition to the motor symptoms patients experience cognitive decline eventually resulting in severe disability. Pathologically PD is characterized by neurodegeneration in the substantia nigra pars compacta (SNc) with intracytoplasmic inclusions known as Lewy bodies. In addition to the SNc there is neurodegeneration in other areas including cerebral cortex, raphe nuclei, locus ceruleus, nucleus basalis of meynert, cranial nerves and autonomic nervous system. Recent evidence supports the role of inflammation in Parkinson's disease. Apoptosis has been shown to be one of the pathways of cell death in PD. Minocycline, a tetracycline derivative is a caspase inhibitor, and also inhibits the inducible nitric oxide synthase which are important for apoptotic cell death. Furthermore, Minocycline has been shown to block microglial activation of 6-hydroxydopamine and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned parkinsonism animal models and protect against nigrostriatal dopaminergic neurodegeneration. In this review, we present the current experimental evidence for the potential use of tetracycline derivative, minocycline, as a neuroprotective agent in PD.

Animals↗
PubMed2004

A rare case of porphyria.

INTRODUCTION: Congenital erythropoietic porphyria is one of the rare forms of an intriguing group of metabolic disorders known as porphyrias. Less than 200 cases have been reported in the literature. CLINICAL PRESENTATION: We report the case of a 27-year-old gentleman who had the clinical profile suggestive of porphyria, now presenting with anaemia. The type of porphyria was found to be congenital erythropoietic porphyria by biochemical assay and cause for anaemia was haemolysis, a well-known association with the erythropoietic porphyrias. TREATMENT: The management of porphyrias is essentially symptomatic. He was treated with blood transfusions and haematinics. CONCLUSION: The patient improved symptomatically and he is on regular followup. With the development of gene therapy, a specific cure for this rare type of porphyria is expected in the near future.

Adult↗
PubMed2004

Derivation of a typology for the classification of risks in emergency medicine.

OBJECTIVES: To develop a graded classification system for risks in emergency medicine. To test the inter-user reliability of this classification system. DESIGN: Prospective collection of data involving emergency department (ED) critical incidents. Derivation of classification system using the collected critical incidents. Comparison of results of classification of a sample of the critical incidents between different users of the system. SETTING: EDs in two teaching hospitals and two district general hospitals (DGHs) in the north west of England. INTERVENTIONS: Observational study. MAIN OUTCOMES: Classification system itself. Results of classification of same critical incidents by different users. RESULTS: 816 critical incidents were identified and used to derive a typology. This typology was found to have inter-user reliability score of 86% (95% confidence intervals 76.4% to 95.6%). CONCLUSIONS: The typology that has been derived is a reliable tool for the classification of risks in emergency medicine.

Diagnostic Errors↗
PubMed2004

Identifying and comparing risks in emergency medicine.

OBJECTIVES: To identify common risk types occurring in emergency departments (EDs). To compare the risks occurring between different emergency departments. DESIGN: Application of a typology of risks to a database of critical incidents. Comparison of results of applying typology to group of critical incidents collected in a uniform manner in four different EDs. SETTING: EDs in two teaching hospitals and two district general hospitals in the north west of England. INTERVENTIONS: Observational study. MAIN OUTCOME MEASURES: Types of critical incidents identified. Statistical comparisons between EDs. RESULTS: 816 critical incidents were classified. Patient assessment omission failures were the commonest type of failure, accounting for 291 (35.6%) of the critical incidents. Level 1 and level 2 failures accounted for 254 (31.1%) of critical incidents. Significant differences (p = 0.009) were shown between EDs when the categories of critical incidents occurring were compared. No significant differences (p = 0.336) were shown between EDs when the levels of severity of critical incidents occurring were compared. CONCLUSIONS: Large numbers of critical incidents with potentially fatal consequences occur. The types of risks differ significantly between different EDs.

Databases, Factual↗
PubMed2004

Pneumocephalus.

Explore the source record for details and available documents.

Humans↗
PubMed2003

A direct comparison of MR images and thin-layer plastination of the shoulder in the apprehension-test position.

Until now, patients with a shoulder instability being examined using magnetic resonance imaging have been placed in a position with the arm adducted or in the ABER position, as a result of the way conventional MR systems are built. Magnetic resonance systems with an open configuration have made it possible, for the first time, to examine patients in the apprehension-test position, which is a representative diagnostic position for anterior shoulder instability. This new examination position requires an exact understanding of layered imaging anatomy in order to clearly identify MR structures. The purpose of this study is to make possible a direct comparison of the respective abilities of MR cross-section imaging and thin-layer plastination to clearly identify all MR structures of the shoulder positioned in the apprehension-test position. The two shoulders of a body donor were separated and stored in special position supports in the apprehension-test position. The magnetic resonance examination was carried out using a vertically open 0.5-T MR system (Signa SP/i, General Electric Medical Systems, Milwaukee, WI). The following sequences were used: 2D GRE, TR 42.5 ms, TE 20 ms, layer width 3 mm, matrix 512x512, FOV 24 cm. The coronary und transversal MR cross-section segments were subsequently planned in conjunction with thin-layer plastination for both shoulders. Using a direct comparison of MR images with the corresponding thin-layer plastination, it was possible to clearly identify all MR structures.

Aged↗
PubMed2003

First-line sequential high-dose VIP chemotherapy with autologous transplantation for patients with primary mediastinal nonseminomatous germ cell tumours: a prospective trial.

To determine the efficacy of first-line sequential high-dose VIP chemotherapy (HD-VIP) in patients with primary mediastinal nonseminomatous germ cell tumours (GCT), 28 patients were enrolled on a German multicentre trial. High-Dose VIP chemotherapy consisted of 3-4 cycles of dose-intensive etoposide and ifosfamide plus cisplatin, q22days, each cycle followed by autologous peripheral blood stem cell transplantation plus granulocyte-colony stimulating factor (G-CSF) support. One cycle of standard-dose VIP was applied to harvest peripheral blood stem cells. Ten patients had mediastinal involvement as the only manifestation (36 %), 18 of 28 patients had additional metastatic sites, such as lung (n=17; 61%), liver (n=7; 25%), bone (n=5; 18%), lymph nodes (n=3; 11%) and CNS (n=3; 11%). Median follow-up was 43 months (range, 7-113) for all patients and 52 months (range, 22-113) for surviving patients. Nineteen of 28 patients obtained a disease-free status; 11 with HD-VIP alone and eight with adjunctive surgery. In addition, one of the four patients with marker negative partial remission after HD-VIP without resection of residual masses is currently alive. Two patients developed recurrence of GCT or teratoma. Two patients have died due to an associated haematologic disorder. The 2-year progression-free survival and overall survival rates are 64 and 68%, respectively. This report represents a subgroup analysis of 28 patients with mediastinal nonsemina within the German first-line study for 'poor prognosis' GCT. Compared to data of an international database analysis including 253 patients with mediastinal nonseminoma treated with conventional chemotherapy, the results may indicate that HD-VIP results in an approximately 15% survival improvement.

Adult↗
PubMed2003

Non-viral gene therapy: polycation-mediated DNA delivery.

Gene therapy, i.e., the expression in cells of genetic material with therapeutic activity, holds great promise for the treatment of human diseases. A delivery vehicle (vector), of either viral or non-viral origin, must be used to carry the foreign gene into a cell. Viral vectors take advantage of the facile integration of the gene of interest into the host and high probability of its long-term expression but are plagued by safety concerns. Non-viral vectors, although less efficient at introducing and maintaining foreign gene expression, have the profound advantage of being non-pathogenic and non-immunogenic; they are the subject of this review. Polycation-DNA complexes are particularly attractive for non-viral gene therapy. To perform, they have to attach to the target cell surface, be internalized, escape from endosomes, find a way to the nucleus, and, finally, be available for transcription. The clinical usefulness of polycationic vectors depends on elucidating the role each of these steps plays in gene transfer. Recent progress in consequent rational vector improvement is highlighted by our finding of polyethylenimine derivatives more potent and yet less cytotoxic than the 25-kDa polyethylenimine (one of the most effective non-viral vectors). Such vectors could be further modified with cell-targeting ligands to enhance their utility for in vivo applications.

Gene Targeting↗
PubMed2003

[Apoptosis and tumor regression in locally advanced non-small cell lung cancer with neoadjuvant therapy].

Dysregulation of apoptosis is closely associated with malignant cell transformation. On the other hand, apoptosis is induced by chemotherapy or irradiation. Therefore, in 54 patients with locally advanced non-small cell lung cancer (NSCLC, 36 squamous cell carcinomas, 18 adenocarcinomas, stage IIIA/IIIB), apoptotic indices were comparatively analysed before onset and after termination of neoadjuvant therapy. The results were compared with the response to neoadjuvant therapy (extent of therapy-induced tumour regression) as well as the survival times. A statistically significant difference could not be established between pre-therapeutically and post-surgically established apoptotic indices (mean values: 0.93% vs. 1.1%). Neither before therapy nor after surgery did the apoptotic indices show a significant predictive value concerning different overall survival times. These results suggest that neoadjuvant therapy does not modify the extent of apoptosis in lung cancer in the long term. Only a few weeks after the completion of the neoadjuvant chemoradiotherapy this contributes to a net proliferation of the residual tumour tissue which is largely equivalent to that of the untreated tumour.

Adenocarcinoma↗
PubMed2003

[Neoadjuvant therapy in non-small cell lung cancer. Prognostic impact of "mediastinal downstaging"].

In the course of a prospective multicenter study, 40 (26 squamous cell and 14 adenocarcinomas) patients with stage IIIA and IIIB non-small cell lung cancer (NSCLC) were submitted to surgery after neoadjuvant radiochemotherapy. Pretherapeutic clinical lymph node status was compared to the lymph node involvement established in the resection specimens. Therapy-induced tumor regression was classified according to a three-step tumor regression grading system. In 29 patients (72.5%) a downward shift in lymph node involvement could be established,whereas in 27.5% ( n=11) pretherapeutic lymph node status was maintained. Of 26 patients with post-therapeutic N0 or N1 status, 21 revealed less than 10% vital tumor tissue in the resection specimens (regression grades IIb or III). Patients with post-therapeutic N0 or N1 lymph node status were found to have a survival benefit compared to patients with N2 lymph node involvement, though this difference was not statistically significant (p=0.27). On the other hand, tumor regression showed a significant correlation to the overall survival period (p=0.02). Thus, therapy-induced tumor regression grading seems to be a more precise method to predict the outcome of the disease.

Adenocarcinoma↗
PubMed2003

Acrylonitrile-sodium methallylsulfonate copolymer. DSC approach to membrane porosity of foam and hollow fibers.

The porosity of membranes formed from acrylonitrile-sodium methallylsulfonate copolymer was characterized from the analysis of the depression of the melting point of absorbed water. Membranes were obtained either as a foam or as a hollow fiber; the foam consisted of interconnected macrocavities (mean diameter about equal to 1 mm) while the hollow fiber was a symmetric membrane used for blood ultrafiltration. Differential scanning calorimetry (DSC) of water revealed both the Gaussian distribution of pore sizes and correspondingly, their mean size: 5.2 nm for the pores through the walls separating macrocavities in the foam and 5.6 and 10.6 nm associated with two distributions representing nearly equal amounts of absorbed water, for the hollow fiber. In addition to DSC, the water magnetic relaxation showed that the isothermal dehydration of the foam was due to the deswelling of macrocavities while the increasing amount of absorbed water in pores reflects its strong interaction with the polymer.

Acrylic Resins↗
PubMed2003

Induction treatment before surgery for non-small cell lung cancer.

Surgery alone is currently still accepted "standard of care" for patients with operable NSCLC, this includes stages IA and IIB, as well as selected early subsets of IIIA disease. In more advanced and inoperable stage III disease, combinations of chemotherapy and radiotherapy remain the standard treatment approach for patients with good performance status. The role of surgery following induction therapy in these advanced stage III patients is at the moment not conclusively defined. More evidence from randomized trials is clearly needed to tailor treatment for the large number of patients that present in these locally advanced stages. Enrollment of patients into ongoing prospective clinical trials should be encouraged, whenever possible, to further define prognostic factors and improve multimodality strategies in this clinical setting.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2003

[Compression of the spinal cord revealing a seronegative rheumatoid arthritis].

INTRODUCTION: Craniocervical junction damages may result in a compression of the spinal cord. They may be caused by infectious, tumoral or inflammatory processes. Rheumatoid arthritis is probably among rheumatic diseases the most frequent cause of atlantoaxial arthritis. Nevertheless involvement of the craniocervical junction as the presenting symptom of rheumatoid arthritis is a very rare feature. EXEGESIS: We report the case of a 61 years old woman who presented with atlantoaxial involvement and spinal cord compression one year before the diagnosis of a seronegative rheumatoid arthritis. CONCLUSION: Symptomatic craniocervical junction damages may appear. Patients with damages of the craniocervical junction and negative investigations should be followed long-term; an underlying inflammatory disease may become evident after significant delay.

Arthritis, Rheumatoid↗
PubMed2003

Oculomotor impairment during chronic partial sleep deprivation.

OBJECTIVE: The effects of chronic partial sleep (sleep deprivation) and extended sleep (sleep augmentation) followed by recovery sleep on oculomotor function were evaluated in normal subjects to explore the usefulness of oculomotor assessment for alertness monitoring in fitness-for-duty testing. METHODS: Sixty-six commercial drivers (24-62 years, 50m/16f) participated in a 15 day study composed of 3 training days with 8h time in bed per night, 7 experimental days with subjects randomly assigned to either 3, 5, 7, or 9h time in bed, and 3 recovery nights with 8h time in bed. Data from 57 subjects were used. Saccadic velocity (SV), initial pupil diameter (IPD), latency to pupil constriction (CL), and amplitude of pupil constriction (CA) were assessed and correlated with the sleep latency test (SLT), the Stanford sleepiness scale (SSS), and simulated driving performance. RESULTS: Regression analyses showed that SV slowed significantly in the 3 and 5h groups, IPD decreased significantly in the 9h group, and CL increased significantly in the 3h group. SLT and SSS significantly correlated with SV, IPD, CL, and driving accidents for the 3h group, and with CL for the 5h group. Analyses also showed a significant negative correlation between decreasing SV and increasing driving accidents in the 3h group and a significant negative correlation between IPD and driving accidents for the 7h group. CONCLUSIONS: The results demonstrate a sensitivity primarily of SV to sleepiness, and a correlation of SV and IPD to impaired simulated driving performance, providing evidence for the potential utility of oculomotor indicators in the detection of excessive sleepiness and deterioration of complex motor performance with chronic partial sleep restriction. SIGNIFICANCE: This paper shows a relationship between sleep deprivation and oculomotor measures, and suggests a potential utility for oculometrics in assessing operational performance readiness under sleep restricted conditions.

Accidents, Traffic↗
PubMed2003

Results following conservative lateral sphincteromy for the treatment of chronic anal fissures.

INTRODUCTION: Lateral sphincterotomy is now the standard surgical treatment for fissure-in-ano. Healing is achieved in 90% of cases, however, sphincterotomy also carries a significant risk of incontinence. Traditional sphincterotomy comprises of division of the internal sphincter up to the level of the dentate line, a more conservative division could lead to a lower incontinence rate, with an equivalent healing rate. MATERIALS AND METHODS: A total of 65 patients undergoing conservative lateral sphincterotomy under a single operator between January, 1996 and January, 2002 were reviewed. Specific questions were asked regarding overall success of the operation, leakage of fluid, faeces or flatus and recurrence of fissure symptoms. Supplemental data was obtained from a retrospective analysis of the patients' case notes to ascertain demographics, length of hospital stay and complication rate. RESULTS: Sixty of 65 patients responded to our postal questionnaire. The male to female ratio was 1:1 and the mean age 40.3 years of age. No complications were recorded and 97% of patients had achieved fissure healing by the time of their out-patient follow-up (mean 6.9 weeks). Two patients reported new incontinence following their procedure; one patient experienced incontinence of fluid and flatus (1.7%) and the remaining patient complained of incontinence to flatus only. No patients experienced incontinence of faeces. Eleven patients experienced persistent symptoms of pain and bleeding but only 6 of these patients required treatment from their general practitioner which consisted of stool softeners and topical analgesia. No patients required re-operation. CONCLUSION: A conservative division of the internal anal sphincter results in adequate fissure healing and a much lower incontinence rate than that previously recorded in the literature for more traditional divisions of the internal anal sphincter.

Adult↗