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Biomedical subjects

F Campbell

Publications and source records attributed to F Campbell.

At least 37 records · Page 2Linked to original sources

Surgery for midgut carcinoid.

Many clinicians prefer to avoid surgery in patients with carcinoid neoplasia, because of its slow growth and relatively favourable prognosis. Nevertheless, the commonest cause of death in patients with carcinoid is advanced metastatic disease, and both clinical and epidemiological data indicate that the more effectively the disease is ablated, the more long-lasting the benefit. Multidisciplinary management of patients with carcinoid must consider inherited risk, possible multiple carcinoids and/or synchronous non-carcinoid cancer, and the use of a range of investigations that also evaluate the 10% of patients with carcinoid syndrome with or without valvular heart disease. Although primary size is correlated with the presence of nodal with or without liver metastases, carcinoid tumours <1 cm in diameter may be metastatic at presentation, particularly those arising within the small intestine. In the jejunum and ileum, resection of all sizes of carcinoid with local and regional nodes is preferred, to prevent nodal dissemination causing mesenteric ischaemia with or without infarction. Resection of nodal metastases should be undertaken in those with persistent or recurrent nodal disease if possible. Appendiceal and right colonic carcinoids are most effectively treated by right hemicolectomy with local and regional nodal clearance, as for adenocarcinoma. However, for most appendiceal carcinoids which are <1 cm in diameter and non-invasive, appendicectomy alone is sufficient. For appendiceal carcinoids 1-2 cm in diameter, histopathological assessment helps to determine the need for hemicolectomy. Liver resection has been followed by prolonged 5 year survival in several series and is recommended in appropriate patients to attempt cure or to debulk metastatic disease. Liver transplantation has had only qualified success in highly selected patients without extra-hepatic disease in whom other therapies have failed.

Carcinoid Tumor↗

Retinopathy screening in children and adolescents with diabetes.

Diabetic retinopathy is a complication of diabetes that affects the blood vessels of the retina. The majority of patients with diabetic retinopathy exhibit background retinopathy. In approximately 10% of patients, background retinopathy will progress to sight-threatening retinopathy. The aims of our study were to measure the prevalence of retinopathy among our population and to assess the optimal time of screening children and adolescents with type 1 diabetes.

Adolescent↗

How could pathologists improve the initial diagnosis of colitis? Evidence from an international workshop.

BACKGROUND: The taking of multiple colorectal biopsies is in widespread use although there is little research into their benefit for the pathological diagnosis of inflammatory bowel disease. There is also still debate about appropriate morphological criteria for interpreting these biopsies. AIMS: To determine the effect of single versus multiple biopsies on the accuracy of diagnosis and to study the accuracy and reproducibility of the different criteria used in the diagnosis of multiple biopsies by expert and non-expert pathologists. METHOD: Thirteen expert and 12 non-expert international diagnostic histopathologists attended a workshop. Sixty cases with full follow up were viewed, blinded, in two rounds. Diagnoses were made on rectal biopsies and then full colonoscopic series. RESULTS: Experts correctly identified 24% of Crohn's disease cases (non-experts, 12%) from the rectal biopsies. This improved to 64% (non-experts, 60%) with the full series. The accuracy of the diagnosis of ulcerative colitis also improved slightly with the full series from 64% to 74% overall. Experts had a similar (moderate) level of agreement and accuracy to non-experts. For Crohn's disease, the likelihood ratios (LR) for the most important individual features were 12.4 for granulomas and 3.3 for focal or patchy inflammation. Features favouring ulcerative colitis were diffuse crypt architectural irregularity (LR, 3.4), general crypt epithelial polymorphs (LR, 3.7), and reduced crypt numbers (LR, 2.9). CONCLUSIONS: A full colonoscopic series gave more accurate diagnosis than a rectal biopsy. Accurate pathologists used the same evidence based criteria for multiple biopsies as for single biopsies.

Biopsy↗

Systematic review of the use of honey as a wound dressing.

OBJECTIVE: To investigate topical honey in superficial burns and wounds though a systematic review of randomised controlled trials. DATA SOURCES: Cochrane Library, MEDLINE, EMBASE, PubMed, reference lists and databases were used to seek randomised controlled trials. Seven randomised trials involved superficial burns, partial thickness burns, moderate to severe burns that included full thickness injury, and infected postoperative wounds. REVIEW METHODS: Studies were randomised trials using honey, published papers, with a comparator. Main outcomes were relative benefit and number-needed-to-treat to prevent an outcome relating to wound healing time or infection rate. RESULTS: One study in infected postoperative wounds compared honey with antiseptics plus systemic antibiotics. The number needed to treat with honey for good wound healing compared with antiseptic was 2.9 (95% confidence interval 1.7 to 9.7). Five studies in patients with partial thickness or superficial burns involved less than 40% of the body surface. Comparators were polyurethane film, amniotic membrane, potato peel and silver sulphadiazine. The number needed to treat for seven days with honey to produce one patient with a healed burn was 2.6 (2.1 to 3.4) compared with any other treatment and 2.7 (2.0 to 4.1) compared with potato and amniotic membrane. For some or all outcomes honey was superior to all these treatments. Time for healing was significantly shorter for honey than all these treatments. The quality of studies was low. CONCLUSION: Confidence in a conclusion that honey is a useful treatment for superficial wounds or burns is low. There is biological plausibility.

Anti-Bacterial Agents↗

Hepatic intra-arterial delivery of a retroviral vector expressing the cytosine deaminase gene, controlled by the CEA promoter and intraperitoneal treatment with 5-fluorocytosine suppresses growth of colorectal liver metastases.

Targeting of colorectal liver metastases by regional gene therapy was tested in a clinically relevant syngeneic model. First, the CEA-CD-113 retroviral vector containing the cytosine deaminase gene controlled by the CEA specific tumour cell promoter, was shown in vitro to convert 5-fluorocytosine to 5-fluorouracil, resulting in cancer cell killing with a large bystander effect. Second, 10 days after the establishment of liver metastases, retroviral vectors were delivered to the liver by hepatic artery injection. After 5-fluorocytosine administration for 7 days, most surface metastases disappeared and tumour volumes were suppressed up to 8.2-fold. The results support the development of this approach for patient treatment.

Animals↗

An element within the 5' untranslated region of human Hsp70 mRNA which acts as a general enhancer of mRNA translation.

The untranslated regions of mRNAs encoding heat-shock proteins have been reported to contain elements important to the post-transcriptional regulation of these key components of the stress response. In this report we describe an element from the 5'UTR of human Hsp70 mRNA that increases the efficiency of mRNA translation. Cloning of this region upstream of the coding sequence of two different reporter genes (firefly luciferase and chloramphenicol acetyltransferase) increases expression of the reporter under normal cell culture conditions by up to an order of magnitude. This effect was observed in three different promoter contexts (HSP, SV40 and CMV) and in six cell lines. The increase in protein production is not accompanied by any alteration in mRNA levels, suggesting that the element facilitates translation. 5' or 3' truncated sequences are ineffective in enhancing reporter expression, suggesting that the activity arises from the secondary structure of the element, rather than from some smaller defined motif. Computer analysis of this region revealed that it is able to form stable secondary structures (DeltaG approximately -292.6 kJ x mol(-1)). The Hsp70 element does not seem to act as an internal ribosome entry site. Incorporation of the sequence into plasmids used for DNA vaccination produces increased antibody responses, confirming that the sequence is functional in primary cells. These data suggest that the 5'UTR of human Hsp70 mRNA plays an important role in determining Hsp70 expression levels, and that it contains an element of general utility in enhancing recombinant protein expression systems.

5' Untranslated Regions↗

An audit of pathology lymph node dissection techniques in pylorus preserving Kausch-Whipple pancreatoduodenectomy specimens.

AIMS: To determine whether or not identifying recognised anatomical groupings of lymph nodes (LNs) improves LN yield in pancreatoduodenectomy resection specimens. METHODS: All the pathology reports from pancreatoduodenectomy resection specimens between January 1997 and September 1999, for one specialist pathologist at the Royal Liverpool University Hospital, were examined retrospectively. The total number of LNs found in each specimen was determined and the method of identifying LNs established for each case. LNs were found using either (1) the UICC TNM anatomical groupings, termed "grouped"; (2) the Japanese Pancreatic Society classification, termed "numbered"; or (3) neither the "grouped" nor "numbered" classification, termed "non-grouped". RESULTS: A total of 50 reports (45 neoplastic, five chronic pancreatitis) were studied, 11 with non-grouped LNs, 14 with grouped LNs, and 25 with numbered LNs, including the five inflammatory cases. A median of 7.0 LNs was found in non-grouped cases, a significantly lower number than in the grouped cases (median, 12.0; Mann-Whitney U, p < 0.039) and numbered cases (median, 17.0; p < 0.0001). There was no significant difference in the LN yield between grouped and numbered cases (p = 0.1066). LNs were found most frequently in the inferior, posterior pancreaticoduodenal, and infrapyloric regions. CONCLUSIONS: A detailed knowledge of the anatomical distribution of LNs in pancreatoduodenectomy resection specimens significantly improves LN yield. It is suggested that illustrations of LN sites in resection specimens should be included in pathology guidelines/proformas to improve LN detection and, therefore, pathological prognostic data.

Humans↗

Human rights issues and employee benefit plans.

Canadians have human rights protections at both provincial and federal levels of government. At the federal level, the most important legislative enactments are the Canadian Charter of Rights and Freedoms (the "Charter") and the Canadian Human Rights Act. Provincially and territorially, human rights are legislatively safeguarded primarily by provincial human rights codes. Both federally and provincially, human rights may also be impacted by a variety of other statutes and regulations such as employment standards acts, workers' compensation acts, occupational health and safety acts, and pay equity legislation.

Canada↗

K-ras oncogene subtype mutations are associated with survival but not expression of p53, p16(INK4A), p21(WAF-1), cyclin D1, erbB-2 and erbB-3 in resected pancreatic ductal adenocarcinoma.

Previous studies of molecular prognostic markers following resection for exocrine pancreatic cancer have produced conflicting results. Our aim was to undertake a comprehensive analysis of potentially useful molecular markers in a large, multicentre patient population and to compare these markers with standard pathological prognostic variables. Formalin-fixed, paraffin-embedded specimens of pancreatic ductal adenocarcinoma were analysed from 157 patients [100 men and 57 women with a median (range) age of 60 (33-77) years] who had undergone pancreatectomy. Immunohistochemistry was used to detect expression of p16(INK4), p53, p21(WAF1), cyclin D1, erbB-2 and erbB-3. Mutations in codons 12 and 13 of the K-ras oncogene were detected by SSCP and sequencing following DNA extraction and amplification by PCR. The median (range) survival post-resection was 12.5 (3-83) months. Abnormalities of p16(INK4), p53, p21(WAF1), cyclin D1, erbB-2 and erbB-3 expression were found in 87%, 41%, 75%, 72%, 33% and 57% of cases, respectively. There was no significant correlation between expression of any of these markers and patient survival. K-ras mutations were found in 73 (75%) of 97 cases with amplifiable DNA. The presence of K-ras mutation alone did not correlate with survival, but there were significant differences in survival according to the type of K-ras mutation (p = 0.0007). Reduced survival was found in patients with GaT, cGT and GcT K-ras mutations compared to GtT, aGT and GaC mutations. In conclusion, survival was associated with type of K-ras mutation but not expression of p16(INK4), p53, p21(WAF1), cyclin D1, erbB-2 and erbB-3.

Adult↗

Feather vs. non-feather bedding for asthma.

BACKGROUND: Two recent epidemiological studies have reported that children using non-feather pillows suffered from more frequent episodes of wheeze than those using feather pillows OBJECTIVES: To evaluate the efficacy of using feather bedding in the control of asthma symptoms. SEARCH STRATEGY: The Cochrane Airways Group asthma clinical trials register, derived from MEDLINE, EMBASE and hand searching of major journals, was searched using the terms: feather OR bed* OR linen* OR pillow SELECTION CRITERIA: Only randomised or controlled clinical trials were to be included. DATA COLLECTION AND ANALYSIS: No trials met the inclusion criteria for the review. MAIN RESULTS: 126 abstracts were identified. Ten of these were identified as possibly meeting the entry criteria, but on review of the full paper not were suitable. The reasons for exclusion were: not a randomised trial (n=6); allocation of bedding type combined with another intervention (n=4). REVIEWER'S CONCLUSIONS: Whilst recent epidemiological studies suggest that feather bedding is associated with less frequent wheeze than man-made fibre fillings, the evidence currently available is insufficient to assess the clinical benefits of feather bedding in the management of asthma.

Asthma↗

Deficiency of IL-2 or IL-6 reduces lymphocyte proliferation, but only IL-6 deficiency decreases the contact hypersensitivity response.

We evaluated the importance of IL-2 and IL-6 in primary antigen-induced proliferation of lymph node cells (LNC) and the induction of contact hypersensitivity (CH). These responses were examined in cytokine-deficient mice following application of the contact sensitizer, oxazolone (OX). Proliferation and induction of IL-6 by LNC from IL-2-deficient (IL-2(-/-)) mice were reduced by approximately 95 %, relative to the proliferation of LNC from IL-2(+/+) mice, although induction and elicitation of CH responses was not significantly affected. In contrast, the proliferation of LNC from sensitized IL-6(- /-) mice was reduced by approximately 50% and the CH response was significantly reduced, relative to responses of IL-6(+/+) mice. Although nonspecific inflammatory responses induced by croton oil were similar in IL-6(+/+) and IL-6(-/-) mice, both the acute inflammatory response to OX and the second phase of the inflammatory response were significantly reduced. Thus IL-2 and IL-6 play a significant role in the total proliferative response of LNC following primary contact sensitization. However, the proliferation they promote is not critical for priming the antigen-specific effector cells responsible for eliciting CH responses and IL-6 appears to be more important for expression of the later phases of acute inflammation and the CH induced by OX.

Animals↗

Measuring clinical performance and outcomes from diabetes information systems: an observational study.

AIMS/HYPOTHESIS: To examine changes in diabetes care provision after the introduction of a district diabetes information system. METHODS: All patients with diabetes registered on the system between 1993 and 1998 (n = 6544) were included in the analysis. Drop-out cohort analysis was used to handle population changes, logistic regression models with general estimating equations were used to examine changes in clinical performance over time. RESULTS: After the introduction of the system, care processes improved appreciably, in both primary and secondary care. The proportion of patients receiving a preventative care review within the calendar year rose from 56% in 1993 to 67% in 1998. The proportion of these in whom each process was completed improved in all categories from 1993 to 1998: blood pressure 96% to 98%; glycaemic check 67% to 93%; lipid check 31% to 68%; renal check 46% to 87%; fundoscopy 79% to 92%; foot screen 87% to 87%. Similarly there was an increase in the proportion of patients achieving intermediate outcome treatment targets (HbA1c < or = 9.0% from 29% to 43%; cholesterol < or = 5.5 mmol/1 5% to 19%; blood pressure < or = 160/90 37% to 46%). CONCLUSION/INTERPRETATION: Our results suggest appreciable improvements in diabetes care between 1993 and 1998. These changes apply to an entire population of patients across primary and shared care. We believe that these improvements could, in part, be attributable to the way in which the district diabetes information system has facilitated the structured cascade of diabetes care.

Cohort Studies↗

Treatment with neutralising antibody against cytokine induced neutrophil chemoattractant (CINC) protects rats against acute pancreatitis associated lung injury.

BACKGROUND: Lung injury manifest clinically as adult respiratory distress syndrome (ARDS) is a common cause of morbidity and mortality following acute pancreatitis (AP). Neutrophils play a critical role in the progression of AP to ARDS. C-x-C chemokines are potent neutrophil chemoattractants and activators and have been implicated in AP. AIMS: To evaluate the effect of blocking the C-x-C chemokine, cytokine induced neutrophil chemoattractant (CINC), in AP on pancreatic inflammation and the associated lung injury in rats. METHODS: AP was induced by hourly intraperitoneal injections of caerulein. Goat anti-CINC antibody was administered either before or after starting caerulein injections to evaluate the prophylactic and therapeutic effects, respectively. Severity of AP was determined by measuring plasma amylase, pancreatic water content, and pancreatic myeloperoxidase (MPO) activity as a measure of neutrophil sequestration in the pancreas. Lung injury was determined by measurement of pulmonary microvascular permeability and lung MPO activity. RESULTS: Treatment with anti-CINC antibody had little effect on caerulein induced pancreatic damage. However, it reduced the caerulein mediated increase in lung MPO activity as well as lung microvascular permeability when administered either prophylactically (lung MPO (fold increase over control): 1.53 (0.21) v. 3.30 (0.46), p<0.05; microvascular permeability (L/P%): 0.42 (0.07) v. 0.77 (0.11), p<0.05) or therapeutically (lung MPO (fold increase over control): 2.13 (0.10) v 4.42 (0.65), p<0.05; microvascular permeability (L/P%): 0.31 (0.05) v 0.79 (0.13), p<0.05). CONCLUSION: Treatment with anti-CINC antibody afforded significant protection against pancreatitis associated lung injury. These results suggest that CINC plays an important role in the systemic inflammatory response in AP.

Acute Disease↗

Consultation skills of medical students before and after changes in curriculum.

The University of Manchester Medical School has adopted problem-based learning as its main educational method, with a change of emphasis from a biomedical to a biopsychosocial approach. The training of junior medical students in clinical interviewing is intended to reinforce and develop their interpersonal skills. We measured the impact of this new curriculum by assessing two intakes of students covering the period before and after its introduction; a third intake was later added to examine the effect of further curriculum adjustments. 86 students, randomly selected, were videorecorded conducting diagnostic interviews with standardized patients 10 weeks after they had started to learn clinical interviewing. Two instruments were developed--a 23-item communication skills scale and a 13-item information-gathering scale and both showed acceptable inter-rater and test-retest reliability. Communication skills did not differ between years. The total score for information-gathering fell by 13% (95% confidence interval -20 to -6%, P < 0.001) in the first year after introduction of the new educational approach but returned to baseline the following year after further modification of the course. Although the new approach yielded no measurable improvement in the process of communication, assessment 10 weeks after the start of interview training may be too early to permit definitive conclusions. We conclude that it is possible to change to a more patient-centred emphasis in teaching medical interviewing. Some initial loss of information content was rectified by adjustment of the course. Our unfavourable early experience highlights the need to evaluate educational change.

Clinical Competence↗

Who should lead?

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Community Health Services↗

What is meant by intention to treat analysis? Survey of published randomised controlled trials.

OBJECTIVES: To assess the methodological quality of intention to treat analysis as reported in randomised controlled trials in four large medical journals. DESIGN: Survey of all reports of randomised controlled trials published in 1997 in the BMJ, Lancet, JAMA, and New England Journal of Medicine. MAIN OUTCOME MEASURES: Methods of dealing with deviations from random allocation and missing data. RESULTS: 119 (48%) of the reports mentioned intention to treat analysis. Of these, 12 excluded any patients who did not start the allocated intervention and three did not analyse all randomised subjects as allocated. Five reports explicitly stated that there were no deviations from random allocation. The remaining 99 reports seemed to analyse according to random allocation, but only 34 of these explicitly stated this. 89 (75%) trials had some missing data on the primary outcome variable. The methods used to deal with this were generally inadequate, potentially leading to a biased treatment effect. 29 (24%) trials had more than 10% of responses missing for the primary outcome, the methods of handling the missing responses were similar in this subset. CONCLUSIONS: The intention to treat approach is often inadequately described and inadequately applied. Authors should explicitly describe the handling of deviations from randomised allocation and missing responses and discuss the potential effect of any missing response. Readers should critically assess the validity of reported intention to treat analyses.

Data Collection↗