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Biomedical subjects

A M Thompson

Publications and source records attributed to A M Thompson.

At least 19 recordsLinked to original sources
PubMed2006

Age threshold for endoscopy and risk of missing upper gastrointestinal malignancy--data from the Scottish audit of gastric and oesophageal cancer.

BACKGROUND: Urgent endoscopy is indicated for suspected upper gastrointestinal malignancy. However, there is limited evidence on the age threshold for performing urgent endoscopy in uncomplicated dyspepsia (that is, without alarm features). AIM: To quantify the risk of missing upper gastrointestinal malignancy within Scotland, if the age threshold for urgent endoscopy in uncomplicated dyspepsia was increased from 45 to 55 years. METHODS: Analysis of data collected prospectively by the Scottish Audit of Gastric and Oesophageal Cancer. 'Alarm' features at presentation were defined as dysphagia, weight loss, gastrointestinal bleeding, anaemia, vomiting, history of gastric surgery and history of peptic ulcer disease. RESULTS: Of the 3293 patients diagnosed with upper gastrointestinal malignancy, 290 (8.8%) patients were <55 years of age. Twenty-one of the patients aged <55 years had no alarm features (0.64% of all patients); 12 were aged 45-55 years and nine were aged <45 years. Only two patients (one aged <45 years) underwent potentially curative surgery. CONCLUSION: Upper gastrointestinal malignancy is uncommon under 55 years of age and most of the patients present with alarm features. Raising the age threshold for endoscopy for new-onset uncomplicated dyspepsia from 45 to 55 years would not impact adversely on the diagnosis or outcome of upper gastrointestinal malignancy.

Adult↗
PubMed2005

Morbidity and mortality rates following gastric cancer surgery and contiguous organ removal, a population based study.

BACKGROUND: Complete surgical (R0) resection remains the only potentially curative intervention for patients with localised gastric cancer. To achieve a curative resection, patients may require complex operations with resection of contiguous organs. The aim of this study was to assess how the extent of surgical resection influenced morbidity, mortality and survival in an aged non-selected population with significant comorbid disease. PATIENTS AND METHODS: Data were extracted from the Scottish Audit of Gastric and Oesophageal Cancer (SAGOC), a prospective population-based audit of all oesophageal and gastric cancers in Scotland between 1997 and 1999 with a minimum of 1-year follow-up. RESULTS: A total of 646 patients underwent surgical exploration for gastric cancer. A significantly higher incidence of chest infections (18.5 vs 11%, p< 0.05) and anastomotic leaks (14.3 vs 2.2%, p< 0.05) were associated with total gastrectomy (n=168) when compared to distal gastrectomy (n=272) resections. A 9.2% mortality rate and a 60% 1-year survival were associated with gastric resection alone. Removal of the spleen (n=131), pancreas (n=30) or liver resection (n=5) was associated with a significantly higher mortality rates, 18.3, 23.3 and 40%, respectively (p< 0.05), and significantly lower 1-year survival rates, 50.9, 39.1 and 20%, respectively (p< 0.05). CONCLUSIONS: The risk of more extensive resection is not balanced by improved survival in this population based series. Extending gastric resection to involve contiguous organs should be confined to highly selected cases.

Adult↗
PubMed2005

Mapping changes in surgical mortality over 9 years by peer review audit.

BACKGROUND: There is increasing public scrutiny of deaths among surgical patients. This analysis sought evidence of changes in practice over time in the management of patients who died under surgical care. METHODS: The surgeons and anaesthetists in National Health Service hospitals providing the care of all surgical patients in Scotland participated in the Scottish Audit of Surgical Mortality (SASM). Data from peer review audit, critical event analysis and individual feedback of deaths while in surgical care over 9 years (1994-2002) were examined for trends over time. RESULTS: Over a 9-year period, 40,448 patients died while in surgical care. Consultant surgeon and anaesthetist involvement in decision making and operating increased significantly (P < 0.001), and death after elective surgery declined to 0.27 per cent of elective operations. Adverse events were more frequently due to failures of hospital systems or process than to individual clinician errors. Fewer adverse events were identified as having contributed to or caused the death of patients over time (P < 0.001). Failure to use deep vein thrombosis (DVT) prophylaxis and failure to use high-dependency or intensive therapy units (HDU/ITU) became less common, once highlighted by the SASM. CONCLUSION: Through continuous peer review audit, the SASM has mapped and may have contributed to changes in surgical and anaesthetic practice over a 9-year period, indicating that the rate of adverse events can be decreased by changing clinician practice (DVT prophylaxis) and provision of facilities (HDU/ITU). Similar approaches should be considered by other medical specialties.

Aged↗
PubMed2005

Could sequential individual peer reviewed mortality audit data be used in appraisal?

BACKGROUND: Surgeons have traditionally monitored mortality as part of their surgical practice. The aim of this study was to determine whether peer review surgical mortality data might be useful in appraisal. METHODS: Since 1994, the Scottish Audit of Surgical Mortality (SASM) has performed critical event analysis of deaths under surgical care in Scotland. The anonymised, peer reviewed records of 16 consenting surgeons from a single Trust were reviewed over a three year period (2000-2002). RESULTS: Compliance with this voluntary audit was high at 97%. Individual surgeon profiles and comparison with colleagues in similar surgical practice demonstrated adverse events were infrequent and usually due to problems with the process of care rather than individual surgeon errors. The number of case note reviews requested increased significantly over the three years (chi square 9.5, p<0.01) although there was no significant change in the mean number of deaths per surgeon (18) or mean number of adverse events per surgeon (4). CONCLUSIONS: The use of sequential individual peer reviewed mortality data for anonymised comparison with local colleagues is now in use in appraisal and has potential for the revalidation process. This could provide reassurance that individual surgeons are complying with the General Medical Council concept of "good clinical practice" and highlight local problems in the process of care.

Humans↗
PubMed2005

A novel form of pRb expressed during normal myelopoiesis and in tumour-associated macrophages.

The retinoblastoma (Rb) tumour suppressor promotes cell cycle exit, terminal differentiation and survival during normal development and is functionally inactivated in most human cancers. We have identified a novel myeloid-specific form of retinoblastoma protein (pRb), termed deltaRb-p70, that exists in vivo as an N-terminally truncated form of full-length pRb. DeltaRb-p70 appears to be the product of alternative translation and is expressed in primary myeloid cells in fetal liver, bone marrow and spleen. It is also expressed in the human myelomonocytic cell line U937 and is down-regulated as U937s are induced to differentiate. We have also detected deltaRb-p70 expression in primary human breast tumours and we have determined that deltaRb-p70 is specifically expressed in tumour-associated macrophages. These data identify a novel mechanism for regulating pRb expression that is unique to the myeloid system.

Animals↗
PubMed2004

Endoscopic palliative treatment for esophageal and gastric cancer: techniques, complications, and survival in a population-based cohort of 948 patients.

BACKGROUND: Under the auspices of the Scottish Audit of Gastric and Esophageal Cancer, we investigated treatment techniques, complications, and survival in a population-based cohort of patients undergoing endoscopic palliative therapy for esophageal or gastric cancer. METHODS: A total of 948 patients undergoing endoscopic palliative therapy were identified prospectively and followed for a minimum of 1 year. RESULTS: Expandable metal stent placement (506 patients) and LASER (117 patients) were the most frequently used treatment options. Stent placement was more common for grade 3 or 4 dysphagia. Delivery of endoscopic palliative therapy varied by region of residence (from 18% to 38% of patients, p < 0.001) but not by deprivation category. Complications were recorded in 16% of patients (155 of 948). Overall survival was 40% (95% confidence interval [CI], 36-43) at 6 months, 17% (95% CI, 14-19) at 12 months, and 10% (95% CI, 8-12%) at 18 months. CONCLUSIONS: These data define the reality of endoscopic palliative therapy for patients with advanced esophageal or gastric cancer and provide a baseline against which future improvements in care can be measured.

Adenocarcinoma↗
PubMed2004

Modulation of long-term potentiation in the rat hippocampus following cocaine self-administration.

Long-lasting neuroadaptations that occur during drug use and remain after withdrawal are thought to contribute to the persisting and compulsive nature of drug addiction and relapse. At the molecular and cellular levels, mechanisms that have been implicated in the normal process of memory formation are increasingly being identified as potential contributors to the persistence of the addicted state. To investigate the effect of cocaine self-administration on synaptic plasticity, rats were allowed to self-administer 0.5 mg/kg/infusion cocaine or 0.9% NaCl during 90 min sessions for 15 consecutive days. These cocaine and saline self-administration subjects were then restricted to their home cages for 3, 30, or 100 days (3, 30, and 100 day cocaine/saline withdrawal groups) before the assessment of the induction and reversal of long-term potentiation (LTP) in the CA1 region of hippocampal slices. The magnitude of LTP was increased in the 3-day cocaine withdrawal group as compared with the 3-day saline withdrawal group, but this effect was short lived, as the 30-day cocaine and saline withdrawal groups exhibited similar LTP magnitudes. Interestingly, LTP was significantly decreased in the 100-day cocaine withdrawal group compared with the 100-day saline withdrawal group. These results support the hypothesis that the capacity for LTP is persistently altered after withdrawal from exposure to an addictive substance. In addition, this alteration can be differentially expressed such that depending upon the duration of the withdrawal period following the last drug exposure, LTP may be enhanced, unchanged, or suppressed.

Adaptation, Physiological↗
PubMed2004

Dissecting the molecular mechanisms of human cancer: translating laboratory advances into clinical practice.

There are multiple molecular mechanisms involved in human cancers with many genes involved, complex interactions and a variety of ways to examine them. Some events are already emerging as clinically important; others will turn out to be bystanders. By focussing on key genes, such as p53, the clinical implications of genetic changes and the pathways they link into are becoming apparent. Using the complex methodologies now available allied to disciplines such as mathematics we are improving our understanding of malignancy. This is beginning to impact on the management of patients with cancer; meanwhile, a good surgical operation performed timeously is still the best chance a patient has of a cure for most types of solid cancers.

Biopsy, Needle↗
PubMed2004

Investigation of the reliability of 24 h urine excretion as a biomarker of isoflavone exposure over time and over a wide range of isoflavone intakes.

OBJECTIVE: To study the variation in genistein + daidzein intake over a 6-month period and test the reliability of 24 h urinary isoflavones as a biomarker of exposure over time. DESIGN: Dietary genistein + daidzein intake was assessed at various time points throughout six months in 15 healthy subjects. Group 1 (n=8) followed nonsupplemented diets and Group 2 (n=7) took a 35 mg/d isoflavone supplement for 3 months and each subject provided a 24 h urine collection, validated with para-aminobenzoic acid, during weeks 7, 15 and 19. Urine was analysed for genistein and daidzein using LC-MS. RESULTS: Isoflavone intake in Groups 1 and 2 ranged from 0.00 to 1.1 mg/d and 0.1 to 53.1 mg/d, respectively. Urine excretion for both groups ranged from 0.20 to 9.56 mg/d. The relationship between 24 h excretion and isoflavone intake is y=0.44 x +/- 0.03(standard deviation) + 1.57; r=0.89, P<0.001. CONCLUSION: The 24 h urinary isoflavones can be used as biomarkers of isoflavone exposure over time.

Adult↗
PubMed2004

The Auckland Cataract Study: 2 year postoperative assessment of aspects of clinical, visual, corneal topographic and satisfaction outcomes.

AIM: To assess clinical, visual, computerised corneal topographic, and subjective satisfaction with visual acuity, in a cohort of subjects 2 years after phacoemulsification surgery in a public hospital in New Zealand. METHODS: Prospective study of a representative sample of 97 subjects (20%) randomly selected from 480 subjects in the original Auckland Cataract Study (ACS) cohort. The clinical assessment protocol was identical to the ACS and included an extensive questionnaire to enable direct comparisons to be made between the two groups. RESULTS: The study population was predominantly female (66%) with a mean age of 76.3 (SD 9.9) years. New systemic and ocular disease affected 18.4% and 10.3% of subjects respectively, and 10.3% required referral to either a general practitioner (2.1%) or ophthalmologist (8.2%). Mean best spectacle corrected visual acuity (BSCVA) was 0.2 (0.2) logMAR units (6/9 Snellen equivalent), with mean spherical equivalent -0.37 (1.01) dioptres (D) and astigmatism -1.07 (0.70) D 2 years postoperatively, compared to mean BSCVA 0.1 (0.2) logMAR units (6/7.5 Snellen equivalent), spherical equivalent -0.59 (1.07) D, and astigmatism -1.14 (0.77) D 4 weeks after surgery. 94.9% of subjects retained a BSCVA of 6/12 or better, irrespective of pre-existing ocular disease. The overall posterior capsule opacification (PCO) rate was 20.4% and this was visually insignificant in all but 3.1% of eyes that had already undergone Nd:YAG posterior capsulotomy. Orbscan II elevation technology demonstrated corneal stability 2 years after uncomplicated phacoemulsification. Although corneal astigmatism was eliminated in approximately half of the subjects 1 month postoperatively, astigmatism showed a tendency to regress towards the preoperative level with local corneal thickening at the site of incision 2 years after cataract surgery. Of fellow eyes, 61.2% had undergone cataract surgery. Overall, 75.3% of subjects were moderately to very satisfied with their current level of visual acuity. CONCLUSION: Two years after cataract surgery subjects are generally satisfied with their current level of vision and distance BSCVA is 6/12 or better in the majority of eyes. Although only a minority of eyes develop sufficient PCO to require capsulotomy 10.3% of eyes develop new vision threatening ocular pathology.

Adult↗
PubMed2003

Analysis of 153 deaths after upper gastrointestinal endoscopy: room for improvement?

BACKGROUND: Upper gastrointestinal (GI) endoscopy is a widely used procedure that is generally considered to be safe. METHODS: Of a total of 33,854 patients who underwent upper gastrointestinal endoscopy during 1999 under the care of surgeons in Scotland, 153 (0.004%) died. We reviewed the case notes of these 153 patients. RESULTS: Death was directly related to endoscopy in 20 of 153 cases (13%), most commonly due to gastrointestinal perforation or acute pancreatitis. Ninety-one percent (139) of the patients undergoing endoscopy were American Society of Anesthesiologists grades (ASA) 3-5, and 88% received intravenous sedation; an anesthetist was present in 31 cases (20%). Oxygen was administered to 45% of patients during the endoscopy. In 56% of the procedures, there was monitoring of electrocardiograms (ECG), pulse oximetry, or blood pressure readings. CONCLUSIONS: Although deaths after endoscopy may be unavoidable, clinicians undertaking upper GI endoscopy or endoscopic retrograde cholangiopancreatography (ERCP) in ASA 3-5 patients should provide oxygen therapy and cardiovascular monitoring, and keep accurate records. The involvement of an anesthetist in airway management and the administration of intravenous sedation should be actively considered.

Acute Disease↗
PubMed2003

Doxorubicin and vinorelbine act independently via p53 expression and p38 activation respectively in breast cancer cell lines.

In the treatment of breast cancer, combination chemotherapy is used to overcome drug resistance. Combining doxorubicin and vinorelbine in the treatment of patients with metastatic breast cancer has shown high response rates; even single-agent vinorelbine in patients previously exposed to anthracyclines results in significant remission. Alterations in protein kinase-mediated signal transduction and p53 mutations may play a role in drug resistance with cross-talk between signal transduction and p53 pathways. The aim of this study was to establish the effects of doxorubicin and vinorelbine, as single agents, in combination, and as sequential treatments, on signal transduction and p53 in the breast cancer cell lines MCF-7 and MDA-MB-468. In both cell lines, increased p38 activity was demonstrated following vinorelbine but not doxorubicin treatment, whether vinorelbine was given prior to or simultaneously with doxorubicin. Mitogen-activated protein kinase (MAPK) activity and p53 expression remained unchanged following vinorelbine treatment. Doxorubicin treatment resulted in increased p53 expression, without changes in MAPK or p38 activity. These findings suggest that the effect of doxorubicin and vinorelbine used in combination may be achieved at least in part through distinct mechanisms. This additivism, where doxorubicin acts via p53 expression and vinorelbine through p38 activation, may contribute to the high clinical response rate when the two drugs are used together in the treatment of breast cancer.

Breast Neoplasms↗
PubMed2002

Risk factors for post-stem cell transplant sinusitis.

An understanding of the factors that place the post-transplant patient at increased risk for sinusitis would help identify patients likely to develop disease and possibly allow for interventions that would decrease the incidence or severity of sinus disease. This retrospective study investigates the ability of screening paranasal sinus computed tomographic scans (CTs), clinical history, and potential risk factors for sinusitis, including history of tobacco use, history of allergies or asthma, IgG level, history of sinusitis, remission status and acute graft-versus-host disease (GVHD) to predict post-transplant sinusitis. Medical records and sinus CTs of 100 allogeneic bone marrow recipients were reviewed. There was no increased risk of developing sinusitis post SCT for patients with significant disease on screening CT, symptoms at time of transplant, a history of tobacco use, asthma or allergies, low IgG level, history of sinusitis or for patients at high risk of relapse. Patients with GVHD were 4.3 times more likely than patients without GVHD to develop sinusitis post transplant (95% CI: 1.7-11.0, P = 0.002). Acute GVHD places patients at greater risk of developing sinus infections.

Adult↗
PubMed2002

Karyotypic aberrations of chromosomes 16 and 17 are related to survival in patients with breast cancer.

BACKGROUND: Breast cancer has a high incidence and associated mortality rate, yet little is known of the sequence of genetic events that underlie the clinical course. METHODS: The study was a comparative genomic hybridization analysis of 40 primary breast cancers with survival data at a mean of 8.4 years. RESULTS: The mean number of aberrations was 9.0, with a mean of 5.5 gains and 3.5 deletions per tumour. The most common aberrations were: gain of 1q (27 of 40), 8q (19 of 40) and 17q (13 of 40), and deletion of 17p (12 of 40) and 8p (11 of 40). These results are consistent with a distinctive pattern of large-scale (karyotypic) genetic change in primary breast cancer. CONCLUSION: The novel findings of this study were that only women who were disease-free had loss of 16q (E-cadherin) in association with a gain of 16p, and 17p13 (p53) loss combined with 17q12 (HER2) amplification was found only in the cancers of women who developed recurrent disease. The karyotypic changes seen in primary breast cancer seem to be associated with outcome and point to the underlying genetic events.

Breast Neoplasms↗
PubMed2002

The role of signal transduction in cancer treatment and drug resistance.

Drug resistance in the treatment of cancer still remains a major clinical challenge, in part due to an insufficient understanding of the pathways by which these drugs interact with the mechanisms underlying cellular behaviour and cancer pathogenesis. Signal transduction involves cell differentiation, proliferation and cell death with alterations in these mechanisms being involved in the pathogenesis of cancer. It has been postulated that such pathways could be linked to anti-cancer drug resistance. Recently, novel approaches to overcome anti-cancer drug resistance through manipulation of signal transduction pathways, have been introduced in clinical trials. In this article we present a review of the current understanding in the field of signal transduction and the existing evidence for its role in drug resistance. We also discuss its clinical relevance with regard to overcoming drug resistance.

Antineoplastic Agents↗