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Biomedical subjects

M James

Publications and source records attributed to M James.

At least 19 recordsLinked to original sources
PubMed2006

Buckle-related complications following surgical repair of retinal dialysis.

AIM: To describe buckle-related complications following surgical repair of retinal dialysis. METHODS: A retrospective study of 28 consecutive cryobuckle procedures for retinal detachments secondary to retinal dialysis is reported, with particular attention directed towards postoperative complications relating to the buckle. Stata 8 statistical software and Fisher's exact test were used to analyse the data. RESULTS: Of the 28 cases, anatomic success was achieved with a single procedure in 26 cases (92.9%). Postoperative complications were seen in 20 cases (71.4%), with complications attributable to the buckle noted in 19 (67.9%). Buckle-related complications included exposure (7; 25%), strabismus (5; 17.9%), and infection (3; 10.7%). Surgical removal of the buckle was indicated in 13 cases (46.4%), typically within the first 6 postoperative months. Of these, the retina remained flat following removal of buckle in 12 cases (92.3%), whereas the retina redetached in one case (7.7%). CONCLUSION: Cryotherapy with explant is an effective primary procedure for the surgical repair of retinal detachment secondary to retinal dialysis. However, there is a high rate of postoperative complications relating to the buckle following this surgical approach, although the buckle can be safely removed without compromising the anatomic success of the primary surgery in the vast majority of cases.

Adolescent↗
PubMed2006

Sorafenib in advanced melanoma: a Phase II randomised discontinuation trial analysis.

The effects of sorafenib--an oral multikinase inhibitor targeting the tumour and tumour vasculature--were evaluated in patients with advanced melanoma enrolled in a large multidisease Phase II randomised discontinuation trial (RDT). Enrolled patients received a 12-week run-in of sorafenib 400 mg twice daily (b.i.d.). Patients with changes in bi-dimensional tumour measurements <25% from baseline were then randomised to sorafenib or placebo for a further 12 weeks (ie to week 24). Patients with > or =25% tumour shrinkage after the run-in continued on open-label sorafenib, whereas those with > or =25% tumour growth discontinued treatment. This analysis focussed on secondary RDT end points: changes in bi-dimensional tumour measurements from baseline after 12 weeks and overall tumour responses (WHO criteria) at week 24, progression-free survival (PFS), safety and biomarkers (BRAF, KRAS and NRAS mutational status). Of 37 melanoma patients treated during the run-in phase, 34 were evaluable for response: one had > or =25% tumour shrinkage and remained on open-label sorafenib; six (16%) had <25% tumour growth and were randomised (placebo, n=3; sorafenib, n=3); and 27 had > or =25% tumour growth and discontinued. All three randomised sorafenib patients progressed by week 24; one remained on sorafenib for symptomatic relief. All three placebo patients progressed by week-24 and were re-started on sorafenib; one experienced disease re-stabilisation. Overall, the confirmed best responses for each of the 37 melanoma patients who received sorafenib were 19% stable disease (SD) (ie n=1 open-label; n=6 randomised), 62% (n=23) progressive disease (PD) and 19% (n=7) unevaluable. The overall median PFS was 11 weeks. The six randomised patients with SD had overall PFS values ranging from 16 to 34 weeks. The most common drug-related adverse events were dermatological (eg rash/desquamation, 51%; hand-foot skin reaction, 35%). There was no relationship between V600E BRAF status and disease stability. DNA was extracted from the biopsies of 17/22 patients. Six had V600E-positive tumours (n=4 had PD; n=1 had SD; n=1 unevaluable for response), and 11 had tumours containing wild-type BRAF (n=9 PD; n=1 SD; n=1 unevaluable for response). In conclusion, sorafenib is well tolerated but has little or no antitumour activity in advanced melanoma patients as a single agent at the dose evaluated (400 mg b.i.d.). Ongoing trials in advanced melanoma are evaluating sorafenib combination therapies.

Adult↗
PubMed2006

Acetic acid-enhanced magnification endoscopy in the diagnosis of specialized intestinal metaplasia, dysplasia and early cancer in Barrett's oesophagus.

BACKGROUND: Barrett's surveillance is prone to sampling error. Aim To determine whether enhanced magnification endoscopy using acetic acid instillation improves diagnostic accuracy of specialized intestinal metaplasia/dysplasia in Barrett's oesophagus. METHODS: We examined the detection rate of the specialized intestinal metaplasia/dysplasia in 64 consecutive patients with Barrett's oesophagus using acetic acid to enhance mucosal pit patterns. Histology was compared with the previous findings at recent conventional surveillance in 62 patients. We also examined the inter-/intra-observer agreement in the assessment of the enhanced magnification endoscopy pit pattern findings. RESULTS: Histology revealed columnar-lined oesophagus in six (9%) patients, specialized intestinal metaplasia in 49 (77%), low-grade dysplasia in five (8%), high-grade dysplasia in one (2%), and adenocarcinoma in three (5%). There was discordance between the histologic findings from conventional surveillance with random biopsy. Fifteen patients (24%) had a histological upgrade with enhanced magnification endoscopy. There was a high detection rate of specialized intestinal metaplasia even in short segment Barrett's oesophagus (74%), and additionally, there were two cancers, one with 2-cm Barrett's oesophagus and one ultra-short (1 cm). The mean kappa values for inter- and intra-observer agreement in assessing the pit patterns were 0.571 (0.041) and 0.709 (0.038), respectively. CONCLUSIONS: Enhanced magnification endoscopy allows clear visualization of the epithelial pit patterns within Barrett's oesophagus, and targeted biopsy results in a high yield of specialized intestinal metaplasia and dysplasia.

Acetic Acid↗
PubMed2006

Identification of transmembrane proteins as potential prognostic markers and therapeutic targets in breast cancer by a screen for signal sequence encoding transcripts.

This study demonstrates, through a combination of stringent screening methods and thorough validation, that it is possible to identify transmembrane proteins preferentially expressed in primary breast tumour cells. mRNA was extracted from tumour cells isolated from invasive breast cancers and it was then subtracted against normal breast tissue mRNA prior to the generation of a signal sequence-trap library. Screening of the library identified 31 positive clones encoding 12 cell-surface and 12 secreted proteins. The expression of a subset of transmembrane genes was then interrogated using a high-throughput method (tissue microarray) coupled with cutting-edge in situ techniques in a large cohort of patients who had undergone uniform adjuvant chemotherapy. Expression of CD98 heavy chain (CD98HC) and low-level expression of the insulin-like growth factor 2 receptor/mannose-6-phosphate receptor (IGF2R/M6PR) correlated with poor patient prognosis in the whole cohort. Expression of bradykinin receptor B1 (BDKRB1) and testis enhanced gene transcript (TEGT) correlated with good prognosis in woman with oestrogen receptor (ER)-negative breast tumours. These results indicate that this combined approach of isolating primary tumour cells, generating a library to specifically isolate signal-sequence-containing transcripts, and in situ hybridization on tissue microarrays successfully identified novel prognostic markers (BDKRB1, CD98hc, and TEGT) and potential transmembrane therapeutic targets (CD98hc) in breast cancer.

Apoptosis Regulatory Proteins↗
PubMed2006

Ovarian cancer death reduction for women at high risk: workload implications for gynaecology services.

Ovarian cancer spreads early, presents late and is difficult to cure. Reducing death rates from ovarian malignancy has focussed on the unaffected females of families with a high chance of a mutant gene such as BRCA1 and BRCA2. We set up a familial ovarian cancer service in a district general hospital in the UK, serving a population of 330,000. The clinical genetics team acted as gatekeepers to the service. Risk assessment, ultrasound and biochemical screening and prophylactic oophorectomy were discussed. Gene testing was offered when appropriate. This study reviews the levels of activity for the first 8 years of the service. In all, 153 women were referred, of whom 34 (16%) did not have significant clinical histories. Of the 114 who fulfilled the UKFOCSS criteria for family history and age, four were quickly found to be gene mutation negative and 20 (17%) declined intervention. A total of 29 (25%) chose prophylactic oophorectomy and 61 (54%) chose ultrasound screening.

Ambulatory Care Facilities↗
PubMed2005

A cost consequences analysis of local corticosteroid injection and physiotherapy for the treatment of new episodes of unilateral shoulder pain in primary care.

OBJECTIVE: Local steroid injections and community-based physiotherapy have been shown to be of similar benefit for treating shoulder pain presenting to primary care. This paper presents a cost consequences analysis of a prospective economic evaluation, conducted alongside a randomized clinical trial (RCT) of corticosteroid injections versus physiotherapy for new episodes of unilateral shoulder pain, to determine the economic implications of injection versus physiotherapy. METHODS: A pragmatic RCT with 207 patients randomized to either physiotherapy (n = 103) or local steroid injection (n = 104) was conducted. The resource inputs required were identified for each treatment arm in terms of capital, staff and consumables. These were measured for the period up to 6 months post-randomization. Outcome measures included shoulder disability, shoulder pain, global assessment of health change and the EQ5D, all at 6 months. A sensitivity analysis was performed around the general practitioner minor surgical fee. RESULTS: Analysis is presented on the 199 patients for which the general practice record review (101 physiotherapy, 98 injection) was available. The total mean costs, per patient, were 71.28 pound sterling for the injection group and 114.60 pound sterling for the physiotherapy group. The difference in average total cost per patient was 43.32 pound sterling (95% bootstrap confidence interval: 16.21 pound sterling, 68.03 pound sterling ). This is a statistically significant difference in cost. Outcome was similar in both groups across all measures following intervention. Smaller mean differences in cost were observed between the treatment groups in the sensitivity analysis, but the difference remained in favour of injection over physiotherapy. CONCLUSIONS: This study has shown, given similar clinical outcomes across the treatment groups, that corticosteroid injections were the cost-effective option for patients presenting with new episodes of unilateral shoulder pain in primary care.

Adult↗
PubMed2005

CHHIPS (Controlling Hypertension and Hypotension Immediately Post-Stroke) Pilot Trial: rationale and design.

RATIONALE: High and low blood pressure (BP) levels are common following acute stroke, with up to 60% of patients being hypertensive (SBP > 160 mmHg) and nearly 20% having relative hypotension (SBP < or = 140 mmHg), within the first few hours of ictus, both conditions being associated with an adverse prognosis. At present, the optimum management of blood pressure in the immediate post-stroke period is unclear. OBJECTIVE: The primary aim of the Controlling Hypertension and Hypotension Immediately Post-Stroke (CHHIPS) Pilot Trial is to assess whether hypertension and relative hypotension, manipulated therapeutically in the first 24 h following acute stroke, affects short-term outcome measures. DESIGN: The CHHIPS Pilot Trial is a UK based multi-centre, randomized, double-blind, placebo-controlled, titrated dose trial. SETTING: Acute stroke and medical units in teaching and district general hospitals, in the UK. PATIENTS: The CHHIPS Pilot Study aims to recruit 2050 patients, with clinically suspected stroke, confirmed by brain imaging, who have no compelling indication or contraindication for BP manipulation. STUDY OUTCOMES: The primary outcome measure will be the effects of acute pressor therapy (initiated < or = 12 h from stroke onset) or depressor therapy (started < or = 24 h post-ictus) on death and dependency at 14 days post-stroke. Secondary outcome measures will include the influence of therapy on early neurological deterioration, the effectiveness of treatment in manipulating BP levels, the influence of time to treatment and stroke type on response and a cost-effectiveness analysis.

Acute Disease↗
PubMed2004

Phase II clinical trial of capecitabine and gemcitabine chemotherapy in patients with metastatic renal carcinoma.

We report a single institution phase II study of gemcitabine 1200 mg m(-2) i.v. on days 1 and 8 and capecitabine 1300 mg m(-2) twice daily on days 1-14 of each 3-week cycle in patients with metastatic renal carcinoma. Patients had a WHO performance status of 0, 1 or 2. Of the 21 enrolled patients, 19 had received prior immunotherapy or chemoimmunotherapy. All had progressive disease at study entry. In all,19 patients had multiple sites of disease. The median duration of metastatic disease was 12.3 months (range 1.2-78.1 months). Three of the 19 evaluable patients achieved a partial response to treatment, with no complete responses, producing an objective overall response rate of 15.8% (95% CI, 3.4-39.6%). The median time to disease progression was 7.6 months, and median overall survival was 14.2 months. Treatment was reasonably well-tolerated, neutropenia being the most frequently observed grade 3 or 4 toxicity, occurring in 57% of patients. Other side effects were consistent with the established toxicity profile of the two drugs, including diarrhoea, palmar-plantar erythema, fatigue, nausea, vomiting and infection. This combination of gemcitabine and capecitabine has modest activity in immunotherapy-refractory metastatic renal carcinoma with manageable toxicity.

Adult↗
PubMed2004

Randomized clinical trial of the effects of preoperative and postoperative oral nutritional supplements on clinical course and cost of care.

BACKGROUND: Postoperative oral nutritional supplementation has been shown to be of clinical benefit. This study examined the clinical effects and cost of administration of oral supplements both before and after surgery. METHODS: This was a randomized clinical trial conducted in three centres. Patients undergoing lower gastrointestinal tract surgery were randomized to one of four groups: group CC received no nutritional supplements, group SS took supplements both before and after surgery, group CS received postoperative supplements only, and group SC were given supplements only before surgery. Preoperative supplements were given from the time it was decided to operate to 1 day before surgery. Postoperative supplements were started when the patient was able to take free fluids and continued for 4 weeks after discharge from hospital. Data collected included weight change, complications, length of stay, nutritional intake, anthropometrics, quality of life and detailed costings covering all aspects of care. RESULTS: Some 179 patients were randomized, of whom 27 were withdrawn and 152 analysed (CC 44, SS 32, CS 35, SC 41). Dietary intake was similar in all four groups throughout the study. Mean energy intake from preoperative supplements was 536 and 542 kcal/day in the SS and SC groups respectively; that 2 weeks after discharge from hospital was 274 and 361 kcal/day in the SS and CS groups respectively. There was significantly less postoperative weight loss in the SS group than in the CC and CS groups (P < 0.050), and significantly fewer minor complications in the SS and CS groups than the CC group (P < 0.050). There were no differences in the rate of major complications, anthropometrics and quality of life. Mean overall costs were greatest in the CC group, although differences between groups were not significant. CONCLUSION: Perioperative oral nutritional supplementation started before hospital admission for lower gastrointestinal tract surgery significantly diminished the degree of weight loss and incidence of minor complications, and was cost-effective.

Adult↗
PubMed2004

Variation in the helminth community structure in spiny mice (Acomys dimidiatus) from four montane wadis in the St Katherine region of the Sinai Peninsula in Egypt.

We compared helminth communities in spiny mice (Acomys dimidiatus) from 4 wadis in the arid montane region of the southern Sinai in Egypt, in a 4-week period in late summer. Total helminth species richness was 14 (8 nematodes, 5 cestodes and 1 acanthocephalan) with 94% of mice carrying at least 1 species and an overall mean species richness of 1.85. The most prevalent parasites were Protospirura muricola (47.8 %) and Dentostomella kuntzi (46.3%). One larval cestode, Joyeuxiella rossicum, represents a new host record. The helminth community was dominated by intestinal nematodes (88.7%) of which 58.2% were arthropod-transmitted heteroxenic species. At the component community level, 70% of the worms were recovered from mice in just two wadis (Gharaba and Tlah) and 48.6 % of intestinal nematodes were from Wadi Gharaba. Although only 7 species of helminths were recorded from Wadi Gharaba, this site gave the highest Berger-Parker dominance index because of P. muricola. P. muricola was also dominant in Wadi El Arbaein whilst Syphacia minuta was the dominant species in Wadis Gebal and Tlah. At the infracommunity level, mean species richness and Brillouin's index of diversity were highest in Wadi Tlah and lowest in Wadi Gebal, and the former was age dependent. Whilst mice from different wadis differed in the nematodes that were most common, those from Wadi Gharaba carried the highest mean number of worms/mouse. The abundance of P. muricola in particular varied markedly between sites: Wadi Gharaba was distinct as the site showing the highest mean worm burden whereas mice from Wadi Gebal were uninfected. None of the directly transmitted oxyuroid nematodes showed significant variation in abundance between wadis, or host sex or age classes. Overall, the single extrinsic factor in the study, site of capture, was more important than the intrinsic factors in explaining variation in helminth communities in the region. We conclude that in the high mountains of southern Sinai, each wadi is distinct in terms of its rodent parasites, and hence we expect spatially different coevolutionary pressures on their hosts, with resultant variation in life-histories.

Age Factors↗
PubMed2002

Economic evaluation of a randomized clinical trial of haemodilution with cell salvage in aortic surgery.

BACKGROUND: This study evaluated the costs of acute normovolaemic haemodilution (ANH) and intraoperative cell salvage (ICS) versus homologous blood transfusion in aortic surgery in a prospective multicentre randomized trial. METHODS: One hundred and forty-five patients were randomized either to standard transfusion practice (homologous) or to a combination of ANH and ICS (autologous). Costs for each inpatient admission were identified. Cell salvage costs were assigned on the assumption that 50 operations were done each year employing a trained cell salvage operator. The results were analysed statistically using bias-corrected bootstrap analysis. RESULTS: Patients who had transfusion of homologous blood received some 251 units and those having a homologous transfusion received 103 units (P = 0.008). There was no difference in morbidity, mortality and duration of hospital stay. Transfusion-related mean costs were similar at 340 UK pounds for patients having a homologous transfusion and 357 UK pounds for those receiving autologous blood (mean difference 17 UK pounds (95 per cent confidence interval [c.i.]--184 UK pounds to 174 UK pounds); P not significant). There was also no significant difference in mean overall costs: 5859 UK pounds for homologous and 5384 UK pounds for autologous transfusion (mean difference--475 UK pounds (95 per cent c.i.--2231 UK pounds to 1342 UK pounds)). Sensitivity analysis showed that costs remained similar for 20 and 150 operations per annum. Exclusion of a dedicated cell salvage operator reduced autologous transfusion costs but did not have a significant impact on overall cost. CONCLUSION: Autologous transfusion is cost neutral in aortic surgery even when surgical activity is low.

Adult↗
PubMed2002

Current status of screening for diabetic retinopathy in the UK.

This article reviews the current status of retinopathy screening schemes in the UK. There is evidence that high-quality diabetic retinopathy screening schemes are in existence but provision is patchy. Many health authorities have ad hoc screening programmes reaching only about 60% of patients, with unacceptable or undocumented efficacy and minimal quality control. Several models of screening are currently in use with the current preferred option being camera-based screening. Digital imaging systems offer the best prospects for image acquisition, although at present evidence of adequate effectiveness only exists for 35 mm film-based systems. The final report of the National Diabetic Retinopathy Screening Programme commissioned by the UK National Screening Committee for inclusion into the national service framework for diabetes, is thus eagerly awaited and should set standards for screening programmes, in order to improve the care of all those with diabetes. Quality assurance will be the main driver in the immediate future of improvements in screening programmes. Research data will provide the evidence to refine techniques and set targets in the longer term, with the emphasis on cost-effectiveness and quality of life.

Cost-Benefit Analysis↗
PubMed2001

In vitro 3'-end endonucleolytic processing defect in a human mitochondrial tRNA(Ser(UCN)) precursor with the U7445C substitution, which causes non-syndromic deafness.

Eukaryotic tRNAs are transcribed as precursors. A 5'-end leader and 3'-end trailer are endonucleolytically removed by RNase P and 3'-tRNase before 3'-end CCA addition, aminoacylation, nuclear export and translation. 3'-End -CC can be a 3'-tRNase anti-determinant with the ability to prevent mature tRNA from recycling through 3'-tRNase. Twenty-two tRNAs punctuate the two rRNAs and 13 mRNAs in long, bidirectional mitochondrial transcripts. Accurate mitochondrial gene expression thus depends on endonucleolytic excision of tRNAs. Various mitochondrial diseases and syndromes could arise from defective tRNA end processing. The U7445C substitution in the human mitochondrial L-strand transcript (U74C directly following the discriminator base of tRNA(Ser(UCN))) causes non-syndromic deafness. The sequence of the precursor (G/UCU) becomes G/CCU, resembling a 3'-tRNase anti-determinant. We demonstrate that a tRNA(Ser(UCN)) precursor with the U7445C substitution cannot be processed in vitro by 3'-tRNase from human mitochondria. A 3'-end processing defect in this tRNA precursor could thus be responsible for mitochondrial disease.

Base Sequence↗
PubMed2001

Contractures in orthopaedic and neurological conditions: a review of causes and treatment.

PURPOSE: To examine the techniques used for the treatment of contracture in the context of current scientific knowledge of muscle. METHOD: Synthesis of data available from MEDLINE, RECAL, EMBASE, the Cochrane Library and relevant texts. RESULTS: The development of contractures through immobilisation, muscle weakness and spasticity is described. The effects of passive stretching, continuous passive movement, serial plastering, splinting, electrical stimulation, botulinum injections and surgical tenotomies in the treatment of contractures in persons with neurological and orthopaedic conditions are identified. The strengths and weaknesses of these modalities are discussed. CONCLUSION: Predisposing factors persist after treatment of contractures thus for treatment to be effective long-term management programmes need to be developed. New treatment techniques, used in series or combined, offer the prospect of improved management of contracture. Scientific and clinical research is needed to investigate the effect of contracture treatment.

Activities of Daily Living↗