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Biomedical subjects

G Brown

Publications and source records attributed to G Brown.

At least 37 records · Page 2Linked to original sources
PubMed2005

Arthroscopic treatment of lateral epicondylitis: clinical and cadaveric studies.

Clinical and cadaveric studies were done to investigate the role of a degenerative fringe of the radiocapitellar complex subluxating in the radiocapitellar joint in patients with lateral epicondylitis. In the clinical study, arthroscopic resection of this capsular complex was done. Thirty patients with recalcitrant symptoms of lateral epicondylitis for a minimum of 9 months had surgery. In all patients at arthroscopy, a collar-like band of radiocapitellar capsular complex was found to impinge on the radial head and subluxate into the radiocapitellar joint with manipulation under direct vision. Histologic analyses of the resected tissue showed hyaline degeneration and fibrosis. There were no complications in this series. Twenty-eight patients had complete relief of symptoms by this procedure within 2 weeks of surgery. The average time until return to work was 7 days. Elbow arthroscopy was done in 34 cadaveric elbows to examine the relationship of the annular ligament, the lateral joint capsule, and the radial head. A degenerative capsular fold impinging on the radial head was seen in 15 elbows. A classification system, based on the relationship of the capsular fold to the radial head is described. In Type 1 (19 elbows), the radial head is completely exposed. In Type 2 (six elbows), there is partial coverage of the radial head by the capsuloligamentous complex without interposition into the joint in any position. In Type 3 elbows (six elbows), there is subluxation of the capsular edge into the joint, whereas in Type 4 elbows (three elbows), the radial head is completely obscured throughout the range of motion. The lesion was equally prevalent in men and women. The arthroscopic findings at the time of surgery in the clinical group were the same as the Grade 2 and Grade 3 changes that were seen in cadaveric specimens.

Aged↗
PubMed2005

The respiratory syncytial virus small hydrophobic protein is phosphorylated via a mitogen-activated protein kinase p38-dependent tyrosine kinase activity during virus infection.

The phosphorylation status of the small hydrophobic (SH) protein of respiratory syncytial virus (RSV) was examined in virus-infected Vero cells. The SH protein was isolated from [35S]methionine- and [33P]orthophosphate-labelled RSV-infected cells and analysed by SDS-PAGE. In each case, a protein product of the expected size for the SH protein was observed. Phosphoamino acid analysis and reactivity with the phosphotyrosine specific antibody PY20 showed that the SH protein was modified by tyrosine phosphorylation. The role of tyrosine kinase activity in SH protein phosphorylation was confirmed by the use of genistein, a broad-spectrum tyrosine kinase inhibitor, to inhibit SH protein phosphorylation. Further analysis showed that the different glycosylated forms of the SH protein were phosphorylated, as was the oligomeric form of the protein. Phosphorylation of the SH protein was specifically inhibited by the mitogen-activated protein kinase (MAPK) p38 inhibitor SB203580, suggesting that SH protein phosphorylation occurs via a MAPK p38-dependent pathway. Analysis of virus-infected cells using fluorescence microscopy showed that, although the SH protein was distributed throughout the cytoplasm, it appeared to accumulate, at low levels, in the endoplasmic reticulum/Golgi complex, confirming recent observations. However, in the presence of SB203580, an increased accumulation of the SH protein in the Golgi complex was observed, although other virus structures, such as virus filaments and inclusion bodies, remained largely unaffected. These results showed that during RSV infection, the SH protein is modified by an MAPK p38-dependent tyrosine kinase activity and that this modification influences its cellular distribution.

Amino Acid Sequence↗
PubMed2005

A qualitative study of paramedics' attitudes to providing prehospital thrombolysis.

OBJECTIVES: To explore paramedics' attitudes to administering prehospital thrombolysis (PHT). METHOD: In-depth interviews with 20 paramedics were recorded and transcribed and analysed for emergent themes using the constant comparative method. RESULTS: Although there was a will to provide PHT because of its benefits to patients, its associated risks, aspects of pay and working conditions, and certain organisational factors undermined the willingness of some paramedics to administer thrombolysis. The eight minute response time standard is a competing imperative which can delay thrombolysis. CONCLUSIONS: A minority of paramedics are likely to be unwilling to deliver PHT unless countervailing imperatives are addressed.

Attitude of Health Personnel↗
PubMed2005

Thin section MRI in multidisciplinary pre-operative decision making for patients with rectal cancer.

High spatial resolution MRI of the rectum is an accurate method of staging rectal cancer. The technique requires attention to detail so that correct planes and scan parameters are used to obtain the best images. A detailed understanding of the pathological features of these tumours is required for image interpretation so that prognostic information beyond the basic T and N staging of the tumour can be obtained. Use of standardized criteria for reporting is reproducible in the multicentre setting and pre-operative multidisciplinary discussion of the MRI features increases the number of operations performed with tumour-free resection margins.

Decision Making↗
PubMed2005

Techniques and trouble-shooting in high spatial resolution thin slice MRI for rectal cancer.

MRI is increasingly advocated as an optimal method of staging rectal cancer. The technique enables depiction of the relationship of tumour to the mesorectal fascia and may thus identify tumours at risk of positive circumferential margin involvement at surgery. Depth of extramural spread may also be accurately measured and tumour deposits within the mesorectum are shown. It is important that a high spatial resolution technique is used in order to accurately depict these features and care should be taken in ensuring that images acquired cover the entire rectal tumour and mesorectum. This paper describes the technique of high spatial resolution rectal cancer imaging and the potential technical pitfalls in acquiring good quality images. Important factors to consider include: adequate scan duration to achieve high spatial resolution images with sufficient signal to noise ratio, careful positioning of the pelvic phased array coil, use of T2 weighted turbo spin-echo rather than T1 weighted imaging and careful planning of scans to ensure that images are obtained perpendicular to the rectal wall.

Humans↗
PubMed2004

Archaeology: formulation of a Roman cosmetic.

The discovery of a small tin canister in London during archaeological excavations of a Roman temple precinct, dated to the middle of the second century AD, is a landmark in the study of this class of artefact. Such discoveries from the Roman world are rare and this is the only one to be found so far with its lid and contents--a whitish medicinal or cosmetic cream--providing a unique opportunity for us to study the ancient formulation.

Animals↗
PubMed2004

An antagonist of retinoic acid receptors more effectively inhibits growth of human prostate cancer cells than normal prostate epithelium.

Screening of synthetic retinoids for activity against prostate carcinoma cell lines has identified antagonists of retinoic acid receptors (RARs) as potent growth inhibitors (Hammond et al, 2001, Br J Cancer 85, 453-462). Here we report that 5 days of exposure to a high-affinity pan-RAR antagonist (AGN194310) abolished growth of prostate carcinoma cells from 14 out of 14 patients, with half-maximal inhibition between 200 and 800 nM. It had similar effects (at approximately 250 nM) on the prostate carcinoma lines LNCaP, DU-145 and PC-3. AGN194310 inhibited the growth of normal prostate epithelium cells less potently, by 50% at approximately 1 microM. The growth of tumour cells was also inhibited more than that of normal cells when RARbeta together with RARgamma, but not RARalpha alone, were antagonised. Treatment of LNCaP cells with AGN194310 arrested them in G1 of cell cycle within 12 h, with an accompanying rise in the level of p21(waf1). The cells underwent apoptosis within 3 days, as indicated by mitochondrial depolarisation, Annexin V binding and DNA fragmentation. Apoptosis was caspase-independent: caspases were neither cleaved nor activated, and DNA fragmentation was unaffected by the pan-caspase inhibitor Z-VAD-FMK. The ability of AGN 194310 to induce apoptosis of prostate cancer cells and its differential effect on malignant and normal prostate epithelial cells suggests that this compound may be useful in the treatment of prostate cancer.

Apoptosis↗
PubMed2004

Effectiveness of preoperative staging in rectal cancer: digital rectal examination, endoluminal ultrasound or magnetic resonance imaging?

In rectal cancer, preoperative staging should identify early tumours suitable for treatment by surgery alone and locally advanced tumours that require therapy to induce tumour regression from the potential resection margin. Currently, local staging can be performed by digital rectal examination (DRE), endoluminal ultrasound (EUS) or magnetic resonance imaging (MRI). Each staging method was compared for clinical benefit and cost-effectiveness. The accuracy of high-resolution MRI, DRE and EUS in identifying favourable, unfavourable and locally advanced rectal carcinomas in 98 patients undergoing total mesorectal excision was compared prospectively against the resection specimen pathological as the gold standard. Agreement between each staging modality with pathology assessment of tumour favourability was calculated with the chance-corrected agreement given as the kappa statistic, based on marginal homogenised data. Differences in effectiveness of the staging modalities were compared with differences in costs of the staging modalities to generate cost effectiveness ratios. Agreement between staging and histologic assessment of tumour favourability was 94% for MRI (kappa=0.81, s.e.=0.05; kappa(W)=0.83), compared with very poor agreements of 65% for DRE (kappa=0.08, s.e.=0.068, kappa(W)=0.16) and 69% for EUS (kappa=0.17, s.e.=0.065, kappa(W)=0.17). The resource benefits resulting from the use of MRI rather than DRE was 67164 UK pounds and 92244 UK pounds when MRI was used rather than EUS. Magnetic resonance imaging dominated both DRE and EUS on cost and clinical effectiveness by selecting appropriate patients for neoadjuvant therapy and justifies its use for local staging of rectal cancer patients.

Adult↗
PubMed2004

In vivo evaluation of [18F]fluoroetanidazole as a new marker for imaging tumour hypoxia with positron emission tomography.

Development of hypoxia-targeted therapies has stimulated the search for clinically applicable noninvasive markers of tumour hypoxia. Here, we describe the validation of [(18)F]fluoroetanidazole ([(18)F]FETA) as a tumour hypoxia marker by positron emission tomography (PET). Cellular transport and retention of [(18)F]FETA were determined in vitro under air vs nitrogen. Biodistribution and metabolism of the radiotracer were determined in mice bearing MCF-7, RIF-1, EMT6, HT1080/26.6, and HT1080/1-3C xenografts. Dynamic PET imaging was performed on a dedicated small animal scanner. [(18)F]FETA, with an octanol-water partition coefficient of 0.16+/-0.01, was selectively retained by RIF-1 cells under hypoxia compared to air (3.4- to 4.3-fold at 60-120 min). The radiotracer was stable in the plasma and distributed well to all the tissues studied. The 60-min tumour/muscle ratios positively correlated with the percentage of pO(2) values <5 mmHg (r=0.805, P=0.027) and carbogen breathing decreased [(18)F]FETA-derived radioactivity levels (P=0.028). In contrast, nitroreductase activity did not influence accumulation. Tumours were sufficiently visualised by PET imaging within 30-60 min. Higher fractional retention of [(18)F]FETA in HT1080/1-3C vs HT1080/26.6 tumours determined by dynamic PET imaging (P=0.05) reflected higher percentage of pO(2) values <1 mmHg (P=0.023), lower vessel density (P=0.026), and higher radiobiological hypoxic fraction (P=0.008) of the HT1080/1-3C tumours. In conclusion, [(18)F]FETA shows hypoxia-dependent tumour retention and is, thus, a promising PET marker that warrants clinical evaluation.

Animals↗
PubMed2004

Electronic transport in a controllably grown carbon nanotube-silicon heterojunction array.

A uniform array of a new type of heterojunction formed between carbon nanotubes and silicon is studied. The heterojunction array was controllably grown with parallel and uniform nanotubes vertically aligned to the silicon substrate using a self-organized nanopore array template. The pronounced rectifying characteristics of the heterojunction were measured with an on/off ratio as high as 10(5) at 4 V. The analysis shows a large and type-I band offset at the heterojunction. The charge transport in the nanotubes is found to be strongly coupled to and limited by the dielectric charging and polarization in the hosting alumina matrix surrounding the nanotubes.

Journal Article↗
PubMed2004

Flat colorectal neoplasms: endoscopic detection, clinical relevance and management.

The prevalence of flat neoplasms in Western countries appears to be similar to Japan. These lesions are difficult to detect but careful examination of the colonic mucosa with the aid of targeted dye spray reveals subtle mucosal changes characteristic of these lesions. Management of flat neoplasms depends on their size, site and on whether the lesions lift after submucosal injection. In this article, we highlight the typical features of flat neoplasms and discuss their optimal management in routine practice.

Adenoma↗
PubMed2004

Neonatal seizures and limb malformations associated with liver-specific complex IV respiratory chain deficiency.

An eight-week-old infant, the fourth child of consanguineous parents presented with intractable neonatal seizures. The mother had two previous miscarriages. The infant initially presented on day one with multifocal myoclonus, complex partial and generalised tonic-clonic seizures. On examination, there were dysmorphic hands and feet, with absent nails and terminal phalanges of the fingers and toes, hepatomegaly, marked axial and peripheral hypotonia and severe global developmental delay. Ophthalmological assessment showed 'salt and pepper' pigmentary retinopathy. The urinary organic acid profile revealed a marked increase in tricarboxylic acid metabolites. Urinary phosphate reabsorption was reduced at 84%. Type I fibre atrophy was seen on muscle histology, and a cytochrome c oxidase deficiency was found only on enzymology of liver tissue. Limb malformations associated with respiratory chain defects have rarely been reported. To our knowledge, this child has the most severe limb anomaly associated with a tissue-specific complex IV respiratory chain defect.

Abnormalities, Multiple↗
PubMed2004

Measurement of tumour size in case selection for breast cancer therapy by clinical assessment and ultrasound.

AIMS: Clinical assessment of tumour size is often used to choose between mastectomy and primary medical therapy. Clinical and imaging modalities may have varying levels of accuracy across the range of tumour sizes. The aim of this study was to compare the accuracy of clinical measurement and ultrasound in discriminating palpable tumours up to 3 cm vs those greater than 3 cm. METHODS: A prospective analysis of 111 consecutive patients with palpable breast cancer was performed. All women had clinical measurement by caliper and ultrasound assessment prior to any needle biopsy. Clinical measurement and ultrasound assessment of size were compared to pathological tumour size of the surgical specimen. RESULTS: Both clinical and ultrasound measurement underestimate the size of larger tumours. The overall accuracy of clinical assessment and ultrasound examination in correctly identifying a 30 mm cut off was 70.3 and 77.5%, respectively. Ultrasound was significantly more accurate at determining the size of tumours <30 mm (p=0.007) but there was no significant difference between both modalities in assessing tumours greater than 30 mm. CONCLUSIONS: Ultrasound assessment of breast cancer size is more accurate than clinical assessment for tumours less than 30 mm. As clinical examination is as accurate on ultrasound for tumours greater than 30 mm, clinical assessment of tumour size alone is adequate to select patients for primary medical therapy or mastectomy.

Adult↗
PubMed2004

A reappraisal of the incremental packing technique for light cured composite resins.

The cuspal flexure caused by a direct placement composite resin was measured using a technique that did not interfere with cuspal movement. Twenty upper premolar teeth with mesial-occlusal-distal (MOD) cavity preparations were restored using a posterior composite resin. Ten teeth were restored using a bulk packing technique and 10 were restored using three 'U' shaped bucco-lingual increments. Total cuspal movement was measured 1 h following the initiation of curing. Bulk placement of the composite resin produced slightly more cuspal movement (12.5 microm) compared with the incremental placement of composite (11.3 microm). This difference was not statistically significant. The technique of incremental packing to reduce cuspal flexure is therefore questioned.

Bicuspid↗
PubMed2004

Phase II study of irinotecan and 5-fluorouracil/leucovorin in patients with primary refractory or relapsed advanced oesophageal and gastric carcinoma.

BACKGROUND: The purpose of this study was to assess the efficacy and toxicity of irinotecan and 5-fluorouracil (5-FU) in primary refractory or relapsed locally advanced or metastatic oesophagogastric (O-G) carcinoma. PATIENTS AND METHODS: Patients with documented progression on or within 3 months of chemotherapy were recruited between July 2000 and May 2002. Irinotecan (180 mg/m(2)) was given with 5-FU (400 mg/m(2) bolus) and leucovorin (folinic acid) (125 mg/m(2)) followed by 5-FU (1200 mg/m(2) infusion over 48 h) every 2 weeks. Response confirmed by computed tomography was assessed at 12 and 24 weeks. RESULTS: Thirty-eight of 40 registered patients (95%) were assessable. Median follow-up was 9.3 months and median age was 59.0 years. Thirty-three patients (86.8%) had metastatic disease and 37 patients (97.4%) had previously received platinum-based chemotherapy. Overall response rate was 29% (95% confidence interval 15.4% to 45.9%) while an additional 34% had stable disease. Improvement in tumour-related symptoms included dysphagia 78.6%, reflux 60.0%, pain 54.5%, anorexia 64.3% and weight loss 72.7%. Grade 3/4 toxicities were anaemia 13.2%, neutropenia 26.4%, febrile neutropenia 5.2%, stomatitis 2.6%, nausea and vomiting 13.2% and diarrhoea 7.9%. Median failure-free survival was 3.7 months and median overall survival was 6.4 months. CONCLUSION: 5-FU/irinotecan is a valuable regimen for second-line treatment in 5-FU/platinum-resistant O-G carcinoma.

Adenocarcinoma↗