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Biomedical subjects

F Campbell

Publications and source records attributed to F Campbell.

At least 19 recordsLinked to original sources

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↗

Posterior lumbar interbody fusion. Association between disability and psychological disturbance in noncompensation patients.

STUDY DESIGN: An observational study of the relation between disability and psychological distress in patients with no on-going compensation claim who underwent posterior lumbar interbody fusion for chronic low back pain. OBJECTIVES: To study the change in the relation between disability and psychological distress after surgical management for low back pain. SUMMARY OF BACKGROUND DATA: Patient-related factors such as an on-going compensation claim and patient psychology are thought to influence the outcome of low back pain management. METHODS: Of the 58 patients who underwent posterior lumbar interbody fusion for low back pain between 1990 and 1995, 53 were observed for a mean duration of 2.7 years after surgery. Oswestry Disability scores and Distress and Risk Assessment Method scores were collected before surgery and at the follow-up examination. RESULTS: Improvement of 10 points on the Oswestry Disability Score was observed in 52.8% of the patients. However, the results in patients who were distressed before surgery were similar to the results observed in healthy patients. The difference in the Oswestry Disability Scores was 3.1 (95% confidence intervals [-9.9, 16.2], P = 0.297). The change in Distress and Risk Assessment Method scores showed a significant relation to change in the Oswestry Disability Scores (P = 0.033). CONCLUSIONS: Postoperative improvement in disability was not found to be related to preoperative psychology as measured by the Distress and Risk Assessment Method score. Change in disability is significantly related to change in distress.

Adult↗

Laser doppler imaging--a new technique for quantifying microcirculatory flow in patients with primary Raynaud's phenomenon and systemic sclerosis.

This was a pilot study to investigate the new technique of laser Doppler imaging (scanning laser Doppler) as a tool to quantify microvascular blood flow in the digits of patients with primary Raynaud's phenomenon (PRP) and systemic sclerosis (SSc), and to determine in the first instance whether the flux patterns obtained differ between patients with SSc, patients with PRP, and healthy control subjects. Laser Doppler images of the dorsum of the hand and fingers were acquired at 23 and 30 degrees C in 17 healthy control subjects, 7 patients with PRP, 9 patients with the diffuse cutaneous variant of SSc, and 24 patients with the limited cutaneous variant of SSc. Different flux parameters were compared between groups. Analysis of variance found significant differences between groups in two tests: maximum difference in flux between fingertips of the same hand at 23 degrees C (P = 0.001) and maximum gradient in flux along a finger ("distal-dorsal" flux difference) at 30 degrees C (P = 0. 019). Post hoc tests highlighted the differences between controls and patients with limited cutaneous SSc. This pilot study suggests that laser Doppler imaging may allow objective measurement of microvascular flow in patients with PRP and SSc. This new technique may overcome many of the problems inherent in single-channel laser Doppler equipment.

Adult↗

New classification of oesophageal and gastric carcinomas derived from changing patterns in epidemiology.

The current ICD-O classification of carcinomas of the oesophagus and stomach causes epidemiological and clinical confusion. This study compares the epidemiological and clinical features of each subtype and subsite of adenocarcinomas of the oesophagus and stomach, to assess requirements for a new classification of these carcinomas. Data were extracted with appropriate validity checks on all cases of oesophageal and gastric carcinomas identified throughout the period 1974-1993 by the Merseyside and Cheshire Cancer Registry, which covers a population of 2.5 million. The incidence of adenocarcinomas of the lower oesophagus and cardia trebled in males, and doubled in females, whereas adenocarcinoma of the subcardia region of the stomach declined in both sexes. Adenocarcinomas of the lower oesophagus and of the cardia were similar for median age at diagnosis, male to female ratio, percentage of patients who smoked and survival; both were significantly different from carcinomas of the subcardia in these respects. These data imply that adenocarcinomas of the lower oesophagus and cardia are the same disease. A new subsite classification of oesophageal and gastric carcinomas is proposed that includes the gastro-oesophageal junction as a distinct subsite, to facilitate surveillance, management and research.

Adenocarcinoma↗

Antibody response to accelerated Hib immunisation in preterm infants receiving dexamethasone for chronic lung disease.

AIM: To study the effect of dexamethasone on the routine immunisation of preterm infants with chronic lung disease. METHODS: Serum samples were obtained before and after immunisation from an unselected cohort of 59 preterm infants. Haemophilus influenzae antibodies were measured using an ELISA method and differences in the geometric mean values between the two groups of babies analysed. RESULTS: Sixteen infants received no dexamethasone. Before and after immunisation antibody titres for those receiving no dexamethasone were 0.16 and 4.63 mcg IgG/ml. Corresponding values for those receiving dexamethasone were 0.10 and 0.51 mcg IgG/ml, respectively. CONCLUSION: Dexamethasone used in the treatment of chronic lung disease seems to significantly affect the antibody response of preterm infants to immunisation against Haemophilus influenzae.

Anti-Inflammatory Agents↗