Gastrointestinal cancer screening and surveillance programmes : a worldwide perspective : part 2

Part 1 of this article can be found through this link: https://www.um.edu.mt/library/oar//handle/123456789/12879Part 2 of this article. Cancer is a leading cause of death worldwide and such deaths are projected to continue to rise, creating significant morbidity and mortality. Devising programmes to detect early cancer, aiming to achieve complete cure, has been high on the agenda of various professional bodies. This paper focuses on the various screening and surveillance programmes around the world, aiming at detecting early gastrointestinal malignancies. Starting with Barretts’ oesophagus, we shall see the different surveillance programmes across countries to detect premalignant stages of oesophageal cancer, while at the same time reviewing the only country in the world, China, which has an oesophageal cancer mass screening programme. Moving to gastric cancer, we shall review Japan’s screening programme, followed by other countries’ measures in surveilling premalignant gastric conditions. Colorectal cancer is the only gastrointestinal cancer where mass screening has been employed in various countries. This will be discussed in detail, with particular emphasis on the British and American systems. We shall also be discussing the surveillance programmes for moderate and high risk patients of colorectal cancer. Finally, we shall also review the different recommendations with regards to screening for hepatocellular carcinoma.peer-reviewe

Gastrointestinal cancer screening and surveillance programmes : a worldwide perspective : part 1

Part 2 of this article can be found through this link: https://www.um.edu.mt/library/oar//handle/123456789/13101Cancer is a leading cause of death worldwide and such deaths are projected to continue to rise, creating significant morbidity and mortality. Devising programmes to detect early cancer, aiming to achieve complete cure, has been high on the agenda of various professional bodies. This paper focuses on the various screening and surveillance programmes around the world, aiming at detecting early gastrointestinal malignancies. Starting with Barretts’ oesophagus, we shall see the different surveillance programmes across countries to detect premalignant stages of oesophageal cancer, while at the same time reviewing the only country in the world, China, which has an oesophageal cancer mass screening programme. Moving to gastric cancer, we shall review Japan’s screening programme, followed by other countries’ measures in surveilling premalignant gastric conditions. Colorectal cancer is the only gastrointestinal cancer where mass screening has been employed in various countries. This will be discussed in detail, with particular emphasis on the British and American systems. We shall also be discussing the surveillance programmes for moderate and high risk patients of colorectal cancer. Finally, we shall also review the different recommendations with regards to screening for hepatocellular carcinoma.peer-reviewe

Accidental severe bronchial aspiration of barium uncovers diagnosis of bronchiectasis

A 77-year-old man, with a history of chronic obstructive pulmonary disease (COPD) and radiotherapy-treated laryngeal malignancy diagnosed 15 years prior, presented with a 1-year history of intermittent dysphagia. As a part of his investigations, a barium swallow was obtained; but during the initial phases of the procedure, the patient aspirated the contrast agent of barium sulphate. A chest radiograph (Fig. 1a), taken few minutes after the aspiration, showed barium within the different segments and subsegments of the bronchial tree bilaterally, and uncovered features, such as irregular dilatation of the bronchial tree, non-tapering of the bronchi, luminal filling defects and lack of bronchial side branches, characteristic of bronchiectasis. This incident precipitated an exacerbation of COPD with type II respiratory failure, requiring bronchodilators, intravenous antibiotics and non-invasive ventilation using a bilevel positive airway pressure machine. On recovery, direct laryngoscopy revealed post-radiotherapy changes but no evidence of tumour recurrence.peer-reviewe

A clinical practice audit of management and outcomes of patients presenting with chest pain to the Medical Admissions Unit

Acute central chest pain accounts for a significant proportion of emergency medical admissions. If chest pain evaluation is systematic & risk-based, it may prevent unnecessary admissions. This audit aims to observe various aspects of management of patients admitted with chest pain; areas needing review are identified and improvements on current practice are considered. The study observed the current practices in 292 admissions for chest pain to the Medical Admissions Unit over a 3 month period. The relative frequency of risk factors and utilisation of resources were observed. Ninety-one patients (31.2%) that were admitted with chest pain had a diagnostic ECG or raised cardiac enzymes. Twenty-one patients (7.2%) had an urgent exercise stress test (EST) whilst 27 patients (9.2%) had an urgent coronary angiogram. In all, 16 patients (5.5 %) were readmitted with a cardiac event and 8 patients (2.7%) died within 3 months. The presence of age >65, diabetes or hypertension were associated with a high rate of adverse events (13.9%, 16.4%, and 11.6% respectively).peer-reviewe

Psychosocial interventions and opioid detoxification for drug misuse: summary of NICE guidance

Drug misuse is an increasing problem that not only impairs the physical and mental health of people who misuse drugs but also negatively affects their families and wider society (for example, in its association with crime). Recently expanded drug services in the United Kingdom involve general practitioners to a considerable degree, who care for at least a third of opioid misusers in treatment. Many clinicians remain pessimistic, however, about the possible benefits of any treatment and how to engage drug users in treatment.1 This article summarises two new NICE guidelines that identify the most effective, safe detoxification regimens for primary and secondary care, the most cost effective psychosocial interventions, and effective ways to promote patient engagement

A high-speed permanent-magnet machine for fault-tolerant drivetrains

This paper details the design considerations of a permanent magnet (PM), three phase, high speed, synchronous machine for fault tolerant operation. A multidisciplinary approach to the optimal design of the machine is adopted targeted at minimising the additional losses resulting from faulty operating conditions and accounting for the remedial control strategy implemented. The design of a closed slot, 6 slots, 4 pole machine is presented. The machine is prototyped and tested to validate the analytical-computational performances predicted in the design and analysis stage under healthy and faulty condition

Radial force control for triple three-phase sectored SPM machines. Part II: Open winding fault tolerant control

A new advanced fault tolerant control technique for a triple three-phase Surface Permanent Magnet (SPM) machine is investigated in this paper. The machine has a nine-phase winding arranged in three sectors and supplied by three different Voltage Source Inverters (VSIs). The proposed current control technique is firstly exploited to avoid the radial force appearance in case of open winding of one machine sector. Then, the radial force fault tolerant control is improved to compensate for a bearing fault or another source of radial force in this open winding condition. Finite element simulations are used to validate the two proposed control techniques. Finally, advantages and drawbacks of the solution are highlighted

Message to the Maltese medical community

On 20th November 2010 I have the honour of becoming Chair of Council of the Royal College of General Practitioners. I shall be the first female Chair for 51 years and only the second female Chair in the history of the College. Perhaps some would say it is not before time that the College had a female Chair, with women making up around 70% of all UK GPs. I am also proud that I am the first Chair ever to be Maltese, both my parents are from Malta and my father, born in Zejtun, was a doctor, qualifying soon after the 2nd World War. Once settled in England, my father became a General Practitioner, working as a single (and then dual) handed GP in East Anglia.peer-reviewe

Radial force control for triple three-phase sectored SPM machines. Part I: Machine model

The radial force control technique for a triple three-phase Surface Permanent Magnet (SPM) machine is investigated in this paper. The machine has a nine-phase winding arranged in three sectors and supplied by three different Voltage Source Inverters (VSI). A machine model is developed, based on the multi space vector approach. The multi space vector current control technique is exploited to control the torque and the radial force. The radial force control can be useful to compensate for a bearing fault or for a rotor eccentricity. Finite element simulations are used to validate the model and the control technique. Finally, criticalities of the control and modelling aspects are discussed

Modulation of Innate Immunity by Varicella Zoster Virus

Varicella zoster virus (VZV) is a ubiquitous human alphaherpesvirus, which causes varicella (chicken pox) during primary infection. During primary infection, the virus infects the skin and gains access to sensory nerve termini. Through retrograde transport, VZV infects neurons in the dorsal root ganglia (DRG) where the virus establishes lifelong latency. VZV can reactivate to cause herpes zoster (shingles), which encompasses a broad variety of complications such as post herpetic neuralgia (PHN), which is defined as neuropathic pain that persists at least 3 months beyond the appearance of the herpes zoster rash. The mechanisms which govern the ability of VZV to establish and maintain lifelong latency, as well as cause PHN are still unclear and could provide therapeutic targets to help prevent and treat PHN. VZV has been shown to regulate various aspects of innate immunity and this has been linked with the ability of the virus to maintain latency. This study aimed to uncover novel mechanisms of VZV innate immunomodulation to increase understanding of contributing factors to both latency maintenance and the establishment of PHN. The ability of VZV to modulate apoptosis, a non-inflammatory form of programmed cell death, has been linked with the ability of the virus to maintain lifelong latency in neuronal cells. VZV open reading frame (ORF) 63 had been associated with the ability of VZV to protect neuronal cells from apoptosis, however this had never been confirmed in human cells. This study (Chapter 2) utilised VZV ORF63 expressing neuronal (SH-SY5Ys) and keratinocyte (HaCaTs) human cell lines, to further characterise the ability of VZV ORF63 to inhibit apoptosis in a cell type specific manner. It was confirmed that VZV ORF63 expressed in isolation could protect SHSY5Ys from apoptosis induction. Interestingly, VZV ORF63 also protected HaCaTs from apoptosis induction and this seemed to be linked to its relocalisation to the cytoplasm during apoptosis. This suggests that VZV ORF63 may be able to protect multiple cell types from apoptosis. Whilst viruses such as VZV can inhibit apoptosis, other aspects of immunity can compensate for viral inhibitory mechanisms. In HSV-1 infection, cytotoxic T cells (CTL) can prevent HSV-1 reactivation and this has been attributed to the granzyme B cleavage of HSV ICP4. In other viral infections, granzyme B cleavage sites in viral 8 gene products can perturb granzyme B cleavage of apoptotic substrates. Interestingly, no apoptosis is evident in the context of the CTL control of HSV-1 reactivation. Natural killer (NK) cells have also been shown to play critical role in the control of alphaherpesviruses infections and utilise granzyme B to induce apoptosis in target cells. Thus, the aim of Chapter 3 was to identify novel VZV and HSV-1 proteins with granzyme B cleavage sites and to assess whether these proteins could modulate NK cell mediated cytotoxicity. VZV ORF4, VZV ORF62 and HSV ICP27 were found to be cleaved by granzyme B, however in an NK cell cytotoxicity assay, only VZV ORF4 was able to inhibit NK cell apoptosis induction in target cells. The granzyme B cleavage site in VZV ORF4 was identified via site directed mutagenesis. The mutation of the granzyme B cleavage site in VZV ORF4 did not alter its ability to protect against NK cell mediated cytotoxicity, suggesting a novel mechanism for NK cell cytotoxicity inhibition by VZV ORF4. Together this data broadens our understanding of VZV immunoevasive mechanisms in the context of innate immunity and highlights a potential role for granzyme B in the modulation of VZV lytic infection and reactivation. The ability of VZV to modulate innate immunity could contribute to the development of PHN, as aspects of innate immunity can alter sensory neuronal functioning. For example, the skin microenvironment can alter peripheral sensory neuron functioning via the release of nociceptive substances and cytokines. VZV can infect and modulate key skin cell types such as keratinocytes which lie in close proximity to sensory neurons. Therefore, this study aimed to characterise VZV modulation of keratinocyte inflammatory transcriptional and secretory profile to identify potential factors which could alter neuronal functioning (Chapter 4). Of the transcripts examined, inflammatory cytokine transcripts were the most regulated by VZV infection, therefore supernatant was analysed for inflammatory cytokines, chemokines and growth factors. VZV infection altered the secretion of various cytokines, chemokines and growth factors in HaCaTs. Interestingly, VZV infection increased interleukin 1 receptor antagonist (IL1-RA) secretion from HaCaTs at all time points examined post infection. Together this suggests that VZV can modulate the inflammatory profile of keratinocytes which could contribute to PHN development. To examine whether strain specific differences in VZV could contribute to PHN development four clinical isolates (2 PHN and 2 non-PHN) were examined in regard 9 to their growth, ability to induce cell death and modulation of ARPE-19 inflammatory cytokine/chemokine expression (Chapter 4). The clinical isolates examined did not exhibit any differences in growth or ability to induce cell death in ARPE-19s. Supernatant from infected cells was analysed to determine whether VZV clinical isolates could regulate inflammatory responses. No differences were noted between isolates; however, it was clear that VZV infection decreased IL-6 secretion and increased IL-1RA secretion. It was also shown that all isolates could downregulate IL- 1 secretion from ARPE-19s suggesting that in the context of the skin, VZV can downregulate inflammatory factors and upregulate anti-inflammatory factors. This alteration of inflammatory factors could contribute to VZV pathogenesis in the skin. Together this work identifies novel VZV immunomodulatory functions which would contribute to the ability of VZV to maintain lifelong latency and alter PHN development