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Biomedical subjects

J Oates

Publications and source records attributed to J Oates.

At least 19 recordsLinked to original sources

Kirsten ras mutations in patients with colorectal cancer: the 'RASCAL II' study.

Researchers worldwide with information about the Kirsten ras (Ki-ras) tumour genotype and outcome of patients with colorectal cancer were invited to provide that data in a schematized format for inclusion in a collaborative database called RASCAL (The Kirsten ras in-colorectal-cancer collaborative group). Our results from 2721 such patients have been presented previously and for the first time in any common cancer, showed conclusively that different gene mutations have different impacts on outcome, even when the mutations occur at the same site on the genome. To explore the effect of Ki-ras mutations at different stages of colorectal cancer, more patients were recruited to the database, which was reanalysed when information on 4268 patients from 42 centres in 21 countries had been entered. After predetermined exclusion criteria were applied, data on 3439 patients were entered into a multivariate analysis. This found that of the 12 possible mutations on codons 12 and 13 of Kirsten ras, only one mutation on codon 12, glycine to valine, found in 8.6% of all patients, had a statistically significant impact on failure-free survival (P = 0.004, HR 1.3) and overall survival (P = 0.008, HR 1.29). This mutation appeared to have a greater impact on outcome in Dukes' C cancers (failure-free survival, P = 0.008, HR 1.5; overall survival P = 0.02, HR 1.45) than in Dukes' B tumours (failure-free survival, P = 0.46, HR 1.12; overall survival P = 0.36, HR 1.15). Ki-ras mutations may occur early in the development of pre-cancerous adenomas in the colon and rectum. However, this collaborative study suggests that not only is the presence of a codon 12 glycine to valine mutation important for cancer progression but also that it may predispose to more aggressive biological behaviour in patients with advanced colorectal cancer.

Adolescent↗

Philadelphia-positive T-ALL in a patient with follicular lymphoma.

Follicular lymphoma is a B cell malignancy prone to transformation into a large cell diffuse histology. This progression may be multi-clonal as determined by IgH rearrangement. Similar multi-clonal occurrences have been described in immunocompromised patients. However, the lymphoma cells remain predominantly of B cell type. Rarely, composite lymphomas with diffuse T cell histology have been reported arising from follicular lymphoma. The development of T cell leukaemia in a patient with a pre-existing B cell malignancy is an extremely rare event. The occurrence of T cell acute lymphoblastic leukaemia (T-ALL) following follicular lymphoma (FL) has not previously been reported. We report a case of Philadelphia positive (Ph+) T cell ALL developing in a patient who previously had FL which may give some insight into the cell of origin and the defects responsible for malignant transformation of the lymphocytes.

Adult↗

HBME-1, MOC-31, WT1 and calretinin: an assessment of recently described markers for mesothelioma and adenocarcinoma.

AIMS: To evaluate HBME-1, WT1, calretinin and MOC-31 in the differential diagnosis of pleural mesothelioma and adenocarcinoma of the lung. METHODS AND RESULTS: Paraffin-embedded formalin-fixed blocks from six reactive pleuras, 42 mesotheliomas and 40 adenocarcinomas were used. Sections were stained for Leu-M1, HBME-1, calretinin, WT1 and MOC-31. Leu-M1 was positive or equivocal in 34% of mesotheliomas and in 78% of adenocarcinomas; reactive pleuras were all negative. HBME-1 was positive or equivocal in 76% of mesotheliomas and in 73% of adenocarcinomas; five reactive pleuras were positive. Calretinin was positive or equivocal in 92% of mesotheliomas and in 73% of adenocarcinomas; two reactive pleura were equivocal and four were positive. WT1 was positive or equivocal in 72% of mesotheliomas (excluding autopsy cases) and in 20% of adenocarcinomas; all reactive pleuras were positive. MOC-31 was positive or equivocal in 5% of mesotheliomas and in 90% of adenocarcinomas; all reactive pleuras were negative. The reaction with Leu-M1 was graded as equivocal in 25% of the adenocarcinomas. All 24 of the autopsy cases of mesothelioma were negative for WT1 and in many operative specimens only the periphery was stained. CONCLUSIONS: Neither calretinin nor HBME-1 are sufficiently discriminatory to be of use, even as members of a panel of antibodies. WT1 shows some promise, but it cannot be used on autopsy material. The utility of MOC-31 is confirmed, and outperforms Leu-M1.

Adenocarcinoma↗

Improving the epilepsy service: the role of the specialist nurse.

There is currently a wide variation in the level of service provided for patients with epilepsy across the UK. Evidence is becoming available to suggest that improvements in local service provision may be achieved through the intervention of a specialist nurse. Using practical examples, this article explores the roles of the epilepsy specialist nurse, and examines how they may benefit patients and improve services. Functions such as liaison, patient assessment and management, counselling, provision of information, education, and audit are considered. It is hoped that the improved co-ordination and management of epilepsy services, that is achieved through specialist nurse intervention, will lead to improved patient outcomes and increased cost-effectiveness.

Epilepsy↗

EP(2) receptor mediates bronchodilation by PGE(2) in mice.

PGE(2) is an important cyclooxygenase product that modulates airway inflammatory and smooth muscle responses. Signal transduction is mediated by four EP receptor subtypes that cause distinct effects on cell metabolism. To determine the role of EP(2) receptor activation, we produced a mouse lacking the EP(2) receptor by targeted gene disruption. The effect of aerosolized PGE(2) and other agonists was measured using barometric plethysmography and by measurements of lung resistance in mechanically ventilated mice. Inhalation of PGE(2) inhibited methacholine responses in wild-type but not in mice lacking the EP(2) receptor [EP(2)(-/-)]. After airway constriction was induced by methacholine aerosol, PGE(2) reduced the airway constriction enhanced pause in wild-type mice (from 0.88 +/- 0.15 to 0.55 +/- 0.06) but increased it in EP(2)(-/-) mice (from 0.73 +/- 0. 08 to 1.27 +/- 0.19). Similar results were obtained in mechanically ventilated mice. These data indicate that the EP(2) receptor mediates the bronchodilation effect of PGE(2).

Administration, Inhalation↗

The impact of patient-centered care on outcomes.

BACKGROUND: We designed this observational cohort study to assess the association between patient-centered communication in primary care visits and subsequent health and medical care utilization. METHODS: We selected 39 family physicians at random, and 315 of their patients participated. Office visits were audiotaped and scored for patient-centered communication. In addition, patients were asked for their perceptions of the patient-centeredness of the visit. The outcomes were: (1) patients' health, assessed by a visual analogue scale on symptom discomfort and concern; (2) self-report of health, using the Medical Outcomes Study Short Form-36; and (3) medical care utilization variables of diagnostic tests, referrals, and visits to the family physician, assessed by chart review. The 2 measures of patient-centeredness were correlated with the outcomes of visits, adjusting for the clustering of patients by physician and controlling for confounding variables. RESULTS: Patient-centered communication was correlated with the patients' perceptions of finding common ground. In addition, positive perceptions (both the total score and the subscore on finding common ground) were associated with better recovery from their discomfort and concern, better emotional health 2 months later, and fewer diagnostic tests and referrals. CONCLUSIONS: Patient-centered communication influences patients' health through perceptions that their visit was patient centered, and especially through perceptions that common ground was achieved with the physician. Patient-centered practice improved health status and increased the efficiency of care by reducing diagnostic tests and referrals.

Adult↗

XML for immediate discharge letters in Scotland.

This paper describes the results of the first UK project to send and receive discharge letters using XML as a message format for clinical data. The SIGN guideline for immediate discharge has broad clinical acceptance across Scotland and forms the basis for the discharge message content. NHS net as a secure private network and X400 as a secure e-mail message format is intended for the final production systems. Internet mail was used for validating. The Scottish Immediate Discharge Project has the advantage of transferring readable clinical information between computer system and giving the receiving GP choice of decoding and saving clinical and administrative data into his practice system. The design of the Document Type Definition was built using the established standard for XML version 1.0. A number of existing discharge letter systems and a variety of written letters were studied. Existing trial standards, including the EDIFACT and CEN standards were taken into consideration. The project worked with the receiving GP system supplier, GPASS, and the NHSiS Information and Statistics Division in defining the DTD for the pilot. GPASS undertook production of a module for their system to parse the XML message into the patient record on the GP system. The system allows the GP to read and print the original document and modify the content prior to storing in the practice system. Care was taken to avoid sending real patient information for the pilot project. SMTP email messages were used rather than X400 because NHS net was not yet implemented at the pilot hospital sites. Resulting messages were parsed into the GP system and validated by a variety of GP users.

Computer Communication Networks↗

Self-reported voice problems among three groups of professional singers.

A vocal health questionnaire was administered to three groups of professional singers and a "friendship-matched" group of nonsingers in Melbourne, Australia. The responses of 79 opera, 57 musical theatre and 31 contemporary (excluding rock) singers and 86 nonsingers were analysed. The questionnaire solicited information regarding biographical data speaking and singing voice-use behaviours, and vocal health over the previous 12 months in terms of experiences of vocal impairment, vocal disability, and handicap. Significant differences between singers and nonsingers in the prevalence and nature of voice problems were reported. Of the singers, 44% reported one or more occurrences of a diagnosed vocal condition compared to 21% of nonsingers and 69% of singers experienced vocal disability compared to only 41% of nonsingers, over the previous 12 months. In contrast, no significant differences were found between the three different styles of singers in their experience of vocal impairment, disability or handicap.

Adolescent↗

Influence of metastatic site as an additional predictor for response and outcome in advanced colorectal carcinoma.

Every year, 31,230 men and women are diagnosed with colorectal carcinoma, and up to 60% of these will ultimately develop advanced disease. However, there is little information to identify which patients are most likely to benefit from palliative chemotherapy. This analysis is unique in evaluating how the site of metastasis influences response and survival. A database of 497 patients treated within randomized clinical trials using 5-Fluorouracil (5FU)-based chemotherapy at the Royal Marsden Hospital was analysed. The potential for site of metastasis as a predictive variable for response to chemotherapy and survival was examined, in addition to other clinical parameters. The presence of liver metastases was a better predictor for overall response than either performance status or number of metastatic sites on presentation. Probability of response was significantly decreased by a raised serum carcinoembryonic antigen (CEA) and presence of peritoneal metastases. In liver metastases, a normal serum albumin was as significant a predictor for response as good performance status. The most important predictor for survival was initial performance status. The number of metastatic sites on presentation had no influence on survival. Site of metastasis can predict for response to 5FU-based chemotherapy and patients should be stratified according to the involved site of metastasis in the future.

Antimetabolites, Antineoplastic↗

Long-term survival after epirubicin, cisplatin and fluorouracil for gastric cancer: results of a randomized trial.

We report the final results of a prospectively randomized study that compared the combination of epirubicin, cisplatin and protracted venous infusion fluorouracil (5-FU) (ECF regimen) with the standard combination of 5-FU, doxorubicin and methotrexate (FAMTX) in previously untreated patients with advanced oesophagogastric cancer. Between 1992 and 1995, 274 patients with adenocarcinoma or undifferentiated carcinoma were randomized from eight oncology centres in the UK and analysed for response and survival. The overall response rate was 46% (95% confidence interval (CI), 37-55%) with ECF, and 21% (95% CI, 13-28%) with FAMTX (P = 0.00003). The median survival was 8.7 months with ECF and 6.1 months with FAMTX (P = 0.0005). The 2-year survival rates were 14% (95% CI, 8-20%) for the ECF arm, and 5% (95% CI, 2-10%) for the FAMTX arm (P = 0.03). Histologically complete surgical resection following chemotherapy was achieved in ten patients in the ECF arm (three pathological complete responses to chemotherapy) and three patients in the FAMTX arm (no pathological complete responses). The ECF regimen resulted in a response and survival advantage compared with FAMTX chemotherapy. The probability of long-term survival following surgical resection of residual disease is increased by this treatment. The high response rates seen with ECF support its use in the neoadjuvant setting.

Antineoplastic Combined Chemotherapy Protocols↗

Correlation of serum measures of nitric oxide production with lupus disease activity.

OBJECTIVE: To determine whether serum measures of nitric oxide production correlate with disease activity in patients with systemic lupus erythematosus (SLE). METHODS: We assayed the levels of serum nitrate/nitrite from 26 patients with SLE followed for 1-3 years and nitrotyrosine levels in sera from 28 additional patients with SLE; sera from 19 controls were tested in both assays. Lupus disease activity was determined via the physician's global assessment, the Lupus Activity Index, and the SLE Disease Activity Index (SLEDAI) at the time of serum collection for the initial set of 26 patients. Statistical correlations were determined using the Wilcoxon rank sum method and one-way ANOVA testing. RESULTS: Serum levels of nitrate/nitrite were significantly higher in 26 patients with SLE compared to 19 controls (SLE, mean 29.5 microM/ml, range 1-438; controls, mean 9.6 microM/ml, range 0-51; p = 0.0004). Overall, there was a significant correlation between serum nitrate/nitrite levels and SLEDAI scores (p = 0.0065). Renal variables within the SLEDAI had the highest correlation with serum nitrate/nitrite (p = 0.0028). Serum nitrotyrosine levels were also significantly higher in patients with SLE versus controls (p = 0.007) and in active SLE versus those with inactive SLE (p = 0.008). CONCLUSION: Serum nitrate/nitrite levels correlated with SLE disease activity, especially nephritis, in the majority of patients studied. Serum nitrotyrosine levels also differentiated controls from patients with lupus and patients with active from those with inactive disease. Due to the ease and low cost of these assays, serum measures of nitric oxide production appear a potentially useful adjunctive laboratory measure of disease activity in SLE and further implicate nitric oxide as an important mediator of disease in SLE.

Adult↗

Prevalence of voice problems in teachers.

Teachers are frequently cited as experiencing a high rate of vocal dysfunction (1-7). Despite considerable research in the area of voice problems in teachers, the prevalence of voice disorders in this group is unknown. This study investigated the prevalence of self-reported voice problems in teachers using a mail survey of a simple random sample of 1168 state school teachers (preschool-Grade 12) in South Australia. As part of the survey, teachers were asked to report voice problems for the day of the survey, during the current teaching year, and during their careers. The response rate was 75%, with 16% of teachers reporting voice problems on the day of the survey, 20% reporting problems during the current teaching year, and 19% reporting problems at some time during their career. Females were twice as likely as males to report voice problems. These findings clearly indicate a need for further investigation of the causes of vocal dysfunction in teachers and for the development of educational programs aimed at preventing voice problems in this group of professional voice users.

Adult↗

Learning voice analysis using an interactive multi-media package: development and preliminary evaluation.

An important outcome of education for speech-language pathology practice is the ability to analyze voices perceptually, a complex task that is often difficult for novices. This article describes an interactive multi-media package, "A Sound Judgement," that is designed to help students develop skills in perceptual voice analysis and to link their perceptions to laryngeal physiology. The package presents a range of clients with vocal impairments at increasing levels of complexity. Each case has a videoed interview, endoscopic views and animations of the larynx, and case history information. Students make perceptual ratings of clients' voices on a format designed specifically for this package and feedback is provided using ratings made by expert speech-language pathologists. High levels of consensus for the perceptual judgments were achieved among the expert raters. Preliminary evaluations by students have demonstrated that "A Sound Judgement" is likely to be a valuable educational tool.

Computer-Assisted Instruction↗

Why do patients with weight loss have a worse outcome when undergoing chemotherapy for gastrointestinal malignancies?

The aim of this study was to examine whether weight loss at presentation, in patients who were to receive chemotherapy for gastrointestinal carcinomas, influences outcome and whether nutritional intervention would be worthwhile. This study was a retrospective review of prospectively gathered data. The outcomes of patients with or without weight loss and treated for locally advanced or metastatic tumours of the oesophagus, stomach, pancreas, colon or rectum were compared. In 1555 such consecutive patients treated over a 6-year period, weight loss at presentation was reported more commonly by men than women (51 versus 44%, P = 0.01). Although patients with weight loss received lower chemotherapy doses initially, they developed more frequent and more severe dose limiting toxicity--specifically plantar-palmar syndrome (P < 0.0001) and stomatitis (P < 0.0001)--than patients without weight loss. Consequently, patients with weight loss on average received 1 month (18%) less treatment (P < 0.0001). Weight loss correlated with shorter failure-free (P < 0.0001, hazard ratio = 1.25) and overall survival (P < 0.0001, hazard ratio = 1.63), decreased response (P = 0.006), quality of life (P < 0.0001) and performance status (P < 0.0001). Patients who stopped losing weight had better overall survival (P = 0.0004). Weight loss at presentation was an independent prognostic variable (hazard ratio = 1.43). The poorer outcome from treatment in patients with weight loss appears to occur because they receive significantly less chemotherapy and develop more toxicity rather than any specifically reduced tumour responsiveness to treatment. These findings provide a rationale for attempting randomised nutritional intervention studies in these patients.

Adenocarcinoma↗

Hypersensitive allergic reactions to bismuth-iodoform-paraffin paste following ear surgery.

The case notes of 185 patients who had bismuth-iodoform-paraffin paste (BIPP) impregnated ribbon gauze used for packing following ear surgery were analysed retrospectively. The incidence of hypersensitive allergic reactions to BIPP was 5.9 per cent and a five-fold increase risk of developing allergic reactions was found in those with previous exposure to BIPP. Where temporalis fascia was used to repair tympanic membrane defects, the incidence of tympanic membrane graft perforations was higher when allergic reactions to BIPP developed post-operatively, compared to non-allergic cases.

Bismuth↗

The evaluation of salivary gland tumours using proliferating cell nuclear antigen.

In order to assess its discriminating and prognostic value, we studied the immunoreactivity for proliferating cell nuclear antigen (PCNA) in tissue from 52 human salivary gland tumours using the murine monoclonal antibody PC10. The PCNA percentage count, namely, the average number of positive nuclei counted per 100 randomly selected tumour cells was recorded for each tumour. Anaplastic carcinoma was used as a positive control and histologically 'normal' salivary gland and tonsil served as a negative control. A PCNA count of 30 per cent was postulated to predict malignancy within a given salivary gland tumour i.e. a PCNA count of 30 per cent or above would indicate malignant potential. This gave a sensitivity of 96.9 per cent and a specificity of 95.2 per cent and a positive predictive value of determining malignancy of 96.8 per cent. We conclude that PCNA immunoreactivity is useful in discriminating between benign and malignant salivary gland tumours and that it may have prognostic value in this diverse group of neoplasms.

Biomarkers, Tumor↗