Assessment of the microbial load of airway clearance devices used by a cohort of children with cystic fibrosis.

BACKGROUND: Positive expiratory pressure (PEP) devices are an important element of the management of cystic fibrosis, and of other respiratory diseases. Whereas there have been reports in the literature of contamination of airway clearance devices and their surfaces by microbial pathogens, there is little evidence available regarding such contamination and its contribution to respiratory infection. AIM: To establish whether pathogenic bacteria can contaminate PEP devices in the context of normal cleaning and maintenance practices. METHODS: Patients' home-use clearance devices were brought to a routine clinic appointment and collected for microbiology sampling and analysis. The patients were provided with replacement devices. Nineteen such devices were collected from 17 patients, reflecting use of multiple devices by some patients. Swabs were taken and cultured from each patient's used device, the patient's airway, as well as from new unopened and unused devices that acted as controls. RESULTS: Seven of 19 devices (37%) tested positive for presence of pathogenic bacteria. Device-cleaning methods varied among patients and non-sterilization methods were found to be ineffective at removing pathogens. Microbial species found on the devices did not correlate with those identified from airway swabs. CONCLUSION: This study demonstrates the presence of pathogens on positive expiratory pressure devices. The potential for transmission of these pathogens to the patient's airway and the risk of infection remains unclear and requires further study.

How do delirium motor subtypes differ in phenomenology and contributory aetiology? a cross-sectional, multisite study of liaison psychiatry and palliative care patients.

OBJECTIVES: To investigate whether delirium motor subtypes differ in terms of phenomenology and contributory aetiology. DESIGN: Cross-sectional study. SETTING: International study incorporating data from Ireland and India across palliative care, old age liaison psychiatry and general adult liaison psychiatry settings. PARTICIPANTS: 1757 patients diagnosed with delirium using criteria from the Diagnostic and Statistical Manual of Mental Disorders, Fourth edition (DSM IV). PRIMARY AND SECONDARY OUTCOME MEASURES: Hyperactive, mixed and hypoactive delirium subtypes were identified using the abbreviated version of the Delirium Motor Subtype Scale. Phenomenology was assessed using the Delirium Rating Scale Revised. Contributory aetiologies were assessed using the Delirium Aetiology Checklist (DEC), with a score >2 indicating that the aetiology was likely or definitely contributory. RESULTS: Hypoactive delirium was associated with dementia, cerebrovascular and systemic infection aetiologies (p<0.001) and had a lower overall burden of delirium symptoms than the other motor subtypes. Hyperactive delirium was associated with younger age, drug withdrawal and the DEC category other systemic aetiologies (p<0.001). Mixed delirium showed the greatest symptom burden and was more often associated with drug intoxication and metabolic disturbance (p<0.001). All three delirium motor subtypes had similar levels of impairment in attention and visuospatial functioning but differed significantly when compared with no subtype (p<0.001). CONCLUSIONS: This study indicates a pattern of aetiology and symptomatology of delirium motor subtypes across a large international sample that had previously been lacking. It serves to improve our understanding of this complex condition and has implications in terms of early detection and management of delirium.

The relationship between post-surgery infection and breast cancer recurrence.

Breast cancer is the second most prevalent form of cancer in women worldwide, with surgery remaining the standard treatment. The adverse impact of the surgery remains controversial. It has been suggested that systemic factors during the postoperative period may increase the risk of recurrence, specifically surgical site infection (SSI). The aim of this review was to critically appraise current published literature regarding the influence of SSIs, after primary breast cancer surgery, on breast cancer recurrence, and to delve into potential links between these. This systematic review adopted two approaches: to identify the incidence rates and risk factors related to SSI after primary breast cancer surgery; and, secondly, to examine breast cancer recurrence following SSI occurrence. Ninety-nine studies with 484,605 patients were eligible in the SSI-focused searches, and 53 studies with 17,569 patients for recurrence-focused. There was a 13.07% mean incidence of SSI. Six-hundred and thirty-eight Gram-positive and 442 Gram-negative isolates were identified, with methicillin-susceptible Staphylococcus aureus and Escherichia coli most commonly identified. There were 2077 cases of recurrence (11.8%), with 563 cases of local recurrence, 1186 cases of distant and 25 cases which recurred both locally and distantly. Five studies investigated the association between SSI and breast cancer recurrence with three concluding that an association did exist. In conclusion, there is association between SSI and adverse cancer outcomes, but the cellular link between them remains elusive. Confounding factors of retrospective study design, surgery type and SSI definition make results challenging to compare and interpret. A standardized prospective study with appropriate statistical power is justified.

Characteristics and outcomes of acute colitis diagnosed on cross-sectional imaging presenting via the emergency department in an Irish academic medical centre.

BACKGROUND AND AIMS: A significant proportion of patients presenting to the Emergency Department with gastrointestinal symptoms that result in cross-sectional imaging receive a radiological diagnosis of colitis. We aimed to review the characteristics, outcomes, and final diagnoses of new emergency department presentations with colitis diagnosed on cross-sectional imaging. METHODS: A radiology database was interrogated to identify patients admitted from the Emergency Department of St James's Hospital whose cross-sectional imaging demonstrated colitis. Baseline demographic data, information on inpatient investigations, final diagnoses, and outcomes were recorded. Adverse outcomes were defined as a requirement for surgery, intensive care unit (ICU) stay, or mortality RESULTS: A total of 118 patients, 67% female, were identified with a median age of 64 years (range 16.9-101.2). Median (range) admission duration was 10 days (1-241). Final colitis diagnoses were infectious (28%), undefined (27%), reactive (18%), inflammatory bowel disease (11%), ischaemic (9%), chemotherapy-associated (3%), diverticular (3%), and medication-associated (1%). Colonic perforation, colectomy, and mortality occurred in 1%, 5%, and 13% of the cohort respectively. On univariate analysis, low haemoglobin, low albumin, high lactate, and male gender were associated with adverse outcomes with the following odds ratios (OR) and 95% confidence intervals (95%CI) were low haemoglobin 1.49 [1.15-1.92] P = 0.002, low albumin 1.16 [1.07-1.25] P = 0.0002, lactate 1.65 [1.13-2.42] P = 0.009, and male gender 3.09 [1.23-7.77] P = 0.019. On multivariate analysis, male gender was associated with adverse outcomes. CONCLUSION: Patients presenting to the Emergency Department with a colitis, requiring an abdominal CT are a heterogenous group with a proportion having concomitant intra-abdominal pathology resulting in critical illness. Hence their is a significant morbidity and mortality observed in this cohort which should not be extrapolated to a general population of patients presenting with colitis. In this cohort of patients, anaemia, hypoalbuminaemia, and elevated lactate in patients presenting to the ED with acute colitis are significantly associated with adverse outcomes. Early recognition of these prognostic factors may identify the cohort of patients who are best managed in a high-dependency setting.

Determination of the Lung Clearance Index (LCI) in a Paediatric Cystic Fibrosis Cohort.

The pathogenesis of CF lung disease may start in infancy. Therefore, it is important to monitor the early stages of its progress. The Exhalyzer D is the first commercially available device designed to measure lung ventilation inhomogeneity at any age. This study was conducted to assess the performance and feasibility of using the Exhalyzer D in a paediatric CF clinic. A total of 91 subjects were recruited (23 controls, and 68 patients with CF). The majority of CF patients (79%) and controls (78%) completed at least two successful washouts. A strong linear correlation was noted between LCI and FEV1. Children with CF under six years of age struggled to perform the washout in a technically correct manner. A clear learning effect was observed, with improved technique and shorter testing times on repeated visits.

Remote preconditioning and major clinical complications following adult cardiovascular surgery: systematic review and meta-analysis.

BACKGROUND: A number of 'proof-of-concept' trials suggest that remote ischaemic preconditioning (RIPC) reduces surrogate markers of end-organ injury in patients undergoing major cardiovascular surgery. To date, few studies have involved hard clinical outcomes as primary end-points. METHODS: Randomised clinical trials of RIPC in major adult cardiovascular surgery were identified by a systematic review of electronic abstract databases, conference proceedings and article reference lists. Clinical end-points were extracted from trial reports. In addition, trial principal investigators provided unpublished clinical outcome data. RESULTS: In total, 23 trials of RIPC in 2200 patients undergoing major adult cardiovascular surgery were identified. RIPC did not have a significant effect on clinical end-points (death, peri-operative myocardial infarction (MI), renal failure, stroke, mesenteric ischaemia, hospital or critical care length of stay). CONCLUSION: Pooled data from pilot trials cannot confirm that RIPC has any significant effect on clinically relevant end-points. Heterogeneity in study inclusion and exclusion criteria and in the type of preconditioning stimulus limits the potential for extrapolation at present. An effort must be made to clarify the optimal preconditioning stimulus. Following this, large-scale trials in a range of patient populations are required to ascertain the role of this simple, cost-effective intervention in routine practice.

Terminology and nomenclature in colonic surgery: universal application of a rule-based approach derived from updates on mesenteric anatomy.

Recent developments in colonic surgery generate exciting opportunities for surgeons and trainees. In the first instance, the anatomy of the entire mesenteric organ has been clarified and greatly simplified. No longer is it regarded as fragmented and complex. Rather it is continuous from duodenojejunal flexure to mesorectum, spanning the gastrointestinal tract between. Recent histologic findings have demonstrated that although apposed to the retroperitoneum, the mesenteric organ is separated from this via Toldt's fascia. These fundamentally important observations underpin the principles of complete mesocolic excision, where the mesocolic package is maintained intact, following extensive mesenterectomy. More importantly, they provide the first opportunity to apply a canonical approach to the development of nomenclature in resectional colonic surgery. In this review, we demonstrate how the resultant nomenclature is entirely anatomic based, and for illustrative purposes, we apply it to the procedure conventionally referred to as right hemicolectomy, or ileocolic resection.

Rapid rise in incidence of Irish paediatric inflammatory bowel disease.

AIMS: To describe the change in incidence of paediatric inflammatory bowel disease (IBD) observed at the National Centre for Paediatric Gastroenterology, Hepatology and Nutrition, and to determine whether the presenting disease phenotype and disease outcomes have changed during the past decade. METHODS: The annual incidence of IBD in Irish children aged <16 years was calculated for the years 2000-2010. Two subsets of patients, group A (diagnosed between 1 January 2000 and 31 December 2001), and group B (diagnosed between 1 January and 31 December 2008) were phenotyped according to the Paris Classification. Phenotype at diagnosis and 2-year follow-up were then compared. RESULTS: 406 new cases of IBD were identified. The incidence was 2.5/100 000/year in 2001, 7.3 in 2008 and 5.6 in 2010, representing a significant increase in the number of new cases of Crohn's disease (CD) and ulcerative colitis (UC). There were 238 cases of CD; 129 of UC; and 39 of IBD unclassified. Comparing groups A and B, no differences were found in disease location at diagnosis or, for CD, in its behaviour. CONCLUSIONS: There has been a substantial and sustained increase in the incidence of childhood UC and CD in Ireland over a relatively short period of time. However, disease phenotype at diagnosis has not changed. At 2 years follow-up, CD appears to progress less frequently than in some neighbouring countries. These variations remain unexplained. Prospective longitudinal studies will help to elucidate further the epidemiology of childhood IBD.

HLA-A, B, Cw, DRB1, DQB1 and DPB1 alleles and haplotypes in the genetically homogenous Irish population.

The frequencies of human leucocyte antigen (HLA) class I and II alleles and haplotypes of 250 Irish unrelated bone marrow donors were determined by high resolution polymerase chain reaction (PCR), using a combination of reverse line blot hybridization and PCR with sequence-specific primers. Phylogenetic analyses indicate that this Irish population is closely related to British, North-western European, American and Australian Caucasian populations. These observations are consistent with recognized historical, geographical, cultural, ethnic and linguistic relationships between these populations and suggest that Irish haematopoietic stem cell transplant recipients have a greater likelihood of finding a phenotypically matched donor within registries based on these populations. HLA-A, B, Cw, DRB1, DQB1 and DPB1 analysis confirms that this young homogenous population is characterized by features of a North-western European anthropological type with limited influence of additional ethnic haplotypes.

Differential expression of matrix metalloproteinase (MMP)-2, MMP-9 and tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2 in non-melanoma skin cancer: implications for tumour progression.

AIMS: To investigate the expression of matrix metalloproteinase (MMP)-2, MMP-9, and tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2 in non-melanoma skin cancer (NMSC) and to compare their expression between different tumour types and with clinicopathological factors. METHODS AND RESULTS: A study of 11 normal skin, 29 Bowen's disease (BD), 40 squamous cell carcinoma (SCC) and 38 basal cell carcinoma (BCC) samples for MMP-2, MMP-9, TIMP-1 and TIMP-2 expression was carried out using immunohistochemistry and in situ hybridization. The expression of all metalloproteinases was greater in tumours than in normal skin. MMP-2 and MMP-9 expression was more extensive in the stroma of SCC than of BCC or BD. TIMP-1 expression was greater in the stroma of BCC than of SCC or BD and TIMP-2 expression was greater in the stroma of SCC than of BD. There was a correlation between increased metalloproteinase expression and depth of lesion (MMP-2 and TIMP-2), inflammation (MMP-2, MMP-9, TIMP-1 and TIMP-2) and microvessel density (MMP-2, MMP-9 and TIMP-2). CONCLUSIONS: MMP-2, MMP-9, TIMP-1 and TIMP-2 play an important role in the pathogenesis of non-melanoma skin cancer, but differ significantly in their expression levels between the tumour types examined. The immunoexpression of these proteins may be useful indicators of cutaneous cancer invasion and progression.

Removal of third molars in Scottish oral and maxillofacial surgery units: a review of practice in 1995 and 2002.

We audited the practice of removal of third molars in Scottish oral and maxillofacial (OMFS) units in 1995 and in 2002. We collected data from anonymous structured postal questionnaires from 12 Scottish OMFS units about patients referred for removal of third molars in 1995 and 11 units in 2002. The percentage of patients who had no treatment increased from 11% in 1995 (102/928) to 16% in 2002 (66/412). The incidence of prophylactic removal of third molars decreased between the two periods. Removal of third molars under local anaesthesia with or without sedation increased from 35% (325/928) in 1995 to 54% (223/412) in 2002. Removal of third molars under general anaesthesia decreased from 54% in 1995 to 30% in 2002.

A multicentre randomized controlled trial of epidural corticosteroid injections for sciatica: the WEST study.

OBJECTIVE: To determine the effectiveness and predictors of response to lumbar epidural corticosteroid injections (ESI) in patients with sciatica. We performed a 12-month, multicentre, double-blind, randomized, placebo-controlled, parallel-group trial in four secondary pain-care clinics in the Wessex Region. METHODS: Two hundred and twenty-eight patients with a clinical diagnosis of unilateral sciatica of 1-18 months' duration were randomized to either three lumbar ESIs of triamcinolone acetonide or interligamentous saline injections at intervals of 3 weeks. The main outcome measure was the Oswestry low back pain disability questionnaire (ODQ). RESULTS: At 3 weeks, the ESI group demonstrated a transient benefit over the placebo group (patients achieving a 75% improvement in ODQ, 12.5 vs 3.7%; number needed to treat, 11.4). No benefit was demonstrated from 6 to 52 weeks. ESIs did not improve physical function, hasten return to work or reduce the need for surgery. There was no benefit of repeated ESIs over single injection. No clinical predictors of response were found. At the end of the study the majority of patients still had significant pain and disability regardless of intervention. CONCLUSIONS: In this pragmatic study, ESIs offered transient benefit in symptoms at 3 weeks in patients with sciatica, but no sustained benefits in terms of pain, function or need for surgery. Sciatica is a chronic condition requiring a multidisciplinary approach. To fully investigate the value of ESIs, they need to be evaluated as part of a multidisciplinary approach.

Combined electric field and ultrasound therapy as a novel anti-tumour treatment.

The permeabilising effects of electric pulses on cell membranes and the use of ultrasound energy of various intensities, for both thermal effects and enhancement of drug and gene delivery, have led to extensive research into the potential applications of these systems in the development of novel anti-cancer treatments. In the present study we have demonstrated for the first time that the application of brief electric pulses 'sensitises' tumour cells to the effects of low intensity ultrasound. The studies were conducted in human tumours established in athymic nude mice and in many instances resulted in the reduction of tumour mass. The combined electric field and ultrasound approach (CEFUS) was applied in vivo to a murine colon adenocarcinoma (C26) and a human oesophageal adenocarcinoma (OE19). The experiments performed demonstrated the anti-tumour effects of the combined therapy. Varying the electrosensitisation parameters used (voltage, waveform, electrode type) contributed to optimise the procedure. Exponential electric pulses with a peak of 1000 V/cm were initially used, but square wave pulses (1000 V/cm, 1 ms, x2, 1 Hz) were found to be just as effective. All ultrasound application parameters were kept constant during the study. The growth rate of C26 tumours treated with CEFUS was significantly reduced with respect to untreated controls at day 7 (96% of average initial tumour volume in CEFUS group versus 615% for controls, P < 0.05). Similar reduction was observed in OE19 tumours treated with CEFUS by day 4 (82% versus 232%, P < 0.032). Our preliminary data suggest that this novel technology could potentially be of wide application in clinical practice for the treatment of solid tumours and is worth further investigation.

The development of novel flexible electrode arrays for the electrochemotherapy of solid tumour tissue. (Potential for endoscopic treatment of inaccessible cancers).

Therapeutic "electroporation" involves application of electric fields to target cells/tissues, thereby rendering their cell membranes transiently porous, thus making feasible the cellular uptake and efficacy of previously impermeant and ineffective therapeutic agents. The objectives of this research are a) the development of flexible electrode arrays for incorporation into microsystem endoscopic devices, and b) the assessment of their efficacy in delivering selected genetic and pharmaceutical anticancer therapies. Gold electrodes were fabricated on flexible polyimide substrates following predictive modeling and simulation of electric fields using FEMLAB software. Subsequent assessment of electroporation efficiency in-vitro involved 1) enumeration of viable tumour cells after delivery of electric pulses and exposure to low concentrations of bleomycin, otherwise known as electrochemotherapy 2) Efficacy of gene delivery by detection of emitted green fluorescence by cells after electroporation with the pEGFP plasmid and 3) In-vivo efficacy of electrochemotherapy in a variety of human solid tumour masses in nude mouse models (xenografts). The flexible electrode system was found to be successful for electrical delivery of plasmids and drugs in-vitro and in-vivo. We found in-vivo complete regression of prostate, colon, oesophageal, and renal cancers with reduced growth rates for fibrosarcoma and breast cell lines. These flexible electrodes are suitable for electrochemotherapy or gene therapy to solid tumours masses and may be fabricated for application to the treatment of some cancers in humans by transcutaneous or endoscopic delivery systems.

Two sets of HLA Class II DRB and DQB1 alleles co-segregate among family members in a single maternal haplotype.

HLA class II typing by sequence specific oligonucleotide probes (SSOP) on the family of a Burkit's Lymphoma patient produced hybridization patterns indicating the presence of two DRB1, and two linked DQB1 genes on the same maternal chromosome. DRB and DQB1 exon 2 amplification products associated with the novel maternal haplotype were identified by DNA typing techniques: These products corresponded to DRB1*0101, DRB1*1501, DRB5*01, DQB1*0501 and DQB1*0602 alleles. These alleles were seen to co-segregate among siblings sharing the same maternal haplotype. The patient, his mother and two of his siblings each appeared to possess elements of three DRB1, DQA1 and DQB1 genes. HLA DNA typing results indicated that a DNA sequence of approximately 100 Kb, spanning the region between, and including, DRB1 and DQB1 genes was inserted into the maternal haplotype. Serological typing on EBV transformed B lymphocytes obtained from the patient's mother showed three expressed DRB1 antigens. Serology on EBV transformed patient's cells also indicated multiple DRB1 antigen expression. The expression of three DRB1 and DQB1 genes on the cells of this patient would make it virtually impossible to obtain a suitably matched unrelated stem cell donor.

Identification and nucleotide sequence of a new null allele, HLA B*3540N.

We report the definition of an HLA class I null allele that has been identified within the B35 group by a combination of serological and molecular typing. This allele, which has been named B*3540N, was detected in a French, potential unrelated hematopoietic stem cell donor of unknown ethnic origin, selected as a probable match for an Irish patient. The presence of the null allele was initially determined by the absence of B35 reactivity by serological typing, in contrast to positive reactions by PCR-SSP and PCR-SSO typing. Subsequent sequencing of clones containing the full genomic sequence of the B*35 allele identified a single nucleotide deletion within exon 4 which resulted in the introduction of a stop codon downstream within exon 4.

Adaptation of bacteria to the intestinal niche: probiotics and gut disorder.

The gastrointestinal tract is a complex ecosystem host to a diverse and highly evolved microbial community composed of hundreds of different microbial species. The interactions that occur between this complex microbial community and the human host have become the focus of scientific research due to increases in the incidence of illnesses associated with deficient or compromised microflora (e.g., gastrointestinal tract infections, inflammatory bowel disease (Crohn's disease and ulcerative colitis), irritable bowel syndrome, antibiotic-induced diarrhea, constipation, food allergies, cardiovascular disease, and certain cancers). Effective multidisciplinary research programs now complement conventional microbiology with molecular ecology techniques to provide culture-independent analysis of the gastrointestinal ecosystem. Furthermore, as we acquire an understanding of gut microflora composition and processes such as intestinal adherence, colonization, translocation, and immunomodulation, we are also elucidating mechanisms by which these can be influenced. This knowledge not only allows scientists to define the activities and interactions of "functional food"-borne beneficial bacteria in the gut, but will also provide the scientific basis for the development of innovative biotechnology-based products tailored to prevent specific diseases and promote overall human gastrointestinal health.