Hughes Abdominal Repair Trial (HART) - Abdominal wall closure techniques to reduce the incidence of incisional hernias: study protocol for a randomised controlled trial.

BACKGROUND: Incisional hernias are common complications of midline closure following abdominal surgery and cause significant morbidity, impaired quality of life and increased health care costs. The 'Hughes Repair' combines a standard mass closure with a series of horizontal and two vertical mattress sutures within a single suture. This theoretically distributes the load along the incision length as well as across it. There is evidence to suggest that this technique is as effective as mesh repair for the operative management of incisional hernias; however, no trials have compared the Hughes Repair with standard mass closure for the prevention of incisional hernia formation following a midline incision. METHODS/DESIGN: This is a 1:1 randomised controlled trial comparing two suture techniques for the closure of the midline abdominal wound following surgery for colorectal cancer. Full ethical approval has been gained (Wales REC 3, MREC 12/WA/0374). Eight hundred patients will be randomised from approximately 20 general surgical units within the United Kingdom. Patients undergoing open or laparoscopic (more than a 5-cm midline incision) surgery for colorectal cancer, elective or emergency, are eligible. Patients under the age of 18 years, those having mesh inserted or undergoing musculofascial flap closure of the perineal defect in abdominoperineal wound closure, and those unable to give informed consent will be excluded. Patients will be randomised intraoperatively to either the Hughes Repair or standard mass closure. The primary outcome measure is the incidence of incisional hernias at 1 year as assessed by standardised clinical examination. The secondary outcomes include quality of life patient-reported outcome measures, cost-utility analysis, incidence of complete abdominal wound dehiscence and C-POSSUM scores. The incidence of incisional hernia at 1 year, assessed by computerised tomography, will form a tertiary outcome. DISCUSSION: A feasibility phase has been completed. The results of the study will be used to inform current and future practice and potentially reduce the risk of incisional hernia formation following midline incisions. TRIAL REGISTRATION NUMBER: ISRCTN 25616490 . Registered on 1 January 2012.

Analysis of a panel of antibodies to APC reveals consistent activity towards an unidentified protein.

Acquisition of truncating mutations in the adenomatous polyposis coli (APC) protein underlies the progression of the majority of sporadic and familial colorectal cancers. As such, the localisation patterns and interacting partners of APC have been extensively studied in a range of systems, relying on the use of a broad panel of antibodies. Until recently, antibodies to APC have been used largely unchecked. However, several recent reports have been invaluable in clarifying the use of a number of antibodies commonly used to detect APC. Here, we analyse the specificity of a further subset of antibodies to APC. We used a panel of six commercially available antibodies (directed to the amino and carboxy termini of APC) and confirm the detection of full-length APC by immunoblotting. We demonstrate that a 150 kDa protein, also reproducibly detected by this panel of antibodies, is unlikely to be APC. We present data for the immunological staining patterns of the APC antibodies and validate the results through RNAi. Using this approach, we confirm that the apical staining pattern, observed by immunofluorescence and previously reported in cell systems, is unlikely to be APC. Finally, we present our data as a summary of APC-antibody specificities for APC.

Death from petrol inhalation after an armoured vehicle rollover.

A case is reported of cardiac arrest in a young man after an armoured vehicle rollover accident. The proposed mechanism of death is myocardial sensitisation to endogenous catecholamines after exposure to petroleum fuel.

Interaction between Ku80 protein and a widely used antibody to adenomatous polyposis coli.

The adenomatous polyposis coli (APC) gene and its expressed product are highly studied because of its role as a tumour-suppressor protein. Inherited mutations in APC lead to the condition known as familial adenomatous polyposis (FAP), which predisposes the affected individuals to colorectal cancer. Furthermore, mutations in APC are found in the majority of sporadic cases of colon cancer. There have been many published studies concerning the cellular localisation of APC, this being fundamental to our understanding of its function, but there has also been much concern over the specificity of certain commercially available antibodies to APC. Here we report that the widely used antibody APC(N15) demonstrates a strong interaction with the Ku80 subunit of the Ku heterodimer under defined experimental conditions. Based on the data presented here, we suggest that APC(N15) is not suitable for many applications used for the study of APC.

Immune responses to native beta(2)-glycoprotein I in patients with systemic lupus erythematosus and the antiphospholipid syndrome.

OBJECTIVE: To identify HLA class II associations with anti beta(2)-glycoprotein I (beta2GPI) antibodies in a cohort of Caucasian patients with systemic lupus erythematosus (SLE) and to determine whether these HLA genotypes act as restriction elements for lymphocyte proliferation to native human beta2GPI in vitro. METHODS: Anti-beta2GPI antibodies were detected in patient sera using enzyme-linked immunosorbent assays (ELISAs). HLA class II alleles (DRB1, DQB1) were determined by polymerase chain reaction-based DNA genotyping. In vitro peripheral blood mononuclear cell (PBMC) responses to native human beta2GPI were measured in a 7-day proliferation assay. RESULTS: We identified three groups of Caucasian SLE patients using these ELISAs. In group 1, 16 out of 18 SLE patients (89%) with anti-beta2GPI antibodies were positive for HLA-DRB1*0401/4/8, DR11 or DRB1*1302 (P=0.001 vs controls) compared with 23 out of 53 patients (43%) in group 2 with anti-cardiolipin antibodies only, 57 out of 151 patients (38%) in group 3 (SLE patients without anticardiolipin antibodies) and 109 out of 225 controls (48%). Fourteen patients with anti-beta2GPI antibodies had greater median stimulation indices to beta2GPI in vitro compared with the 15 controls studied (P=0.04). CONCLUSION: The HLA class II and PBMC proliferation data suggest that beta2GPI may be both a T- and B-cell autoantigen in SLE.

Phase I safety and antigenicity of TA-GW: a recombinant HPV6 L2E7 vaccine for the treatment of genital warts.

A phase I double-blind, randomized, placebo-controlled study was carried out in healthy subjects to assess the safety and immunogenicity of TA-GW, a recombinant HPV6 L2E7 fusion protein vaccine for the treatment of genital warts. Forty-two healthy male volunteers were randomised to receive three intramuscular injections of either 0, 3, 30 or 300 microg of recombinant L2E7 adsorbed onto Alhydrogel. Two vaccination schedules were compared: weeks 0, 1 and 4 (accelerated schedule) and weeks 0, 4 and 8 (classical schedule). Subjects were monitored for adverse events throughout. Immunogenicity was assessed by measuring L2E7 specific in vitro T cell proliferative responses, production of IFNgamma and IL-5 and serum antibodies. Dose-dependent and long-lived T and B cell immune responses were elicited by TA-GW with both vaccination schedules. In conclusion, TA-GW is both safe, well-tolerated and immunogenic. The results allow the selection of the 300-microg vaccine formulation and accelerated vaccination schedule for phase II trials in patients with genital warts.

Phase IIa safety and immunogenicity of a therapeutic vaccine, TA-GW, in persons with genital warts.

A fusion protein vaccine consisting of human papillomavirus 6 L2E7 with Alhydrogel was developed for the treatment of genital warts. Twenty-seven subjects with genital warts received 3 immunizations over 4 weeks in an open-label study. The vaccine was well-tolerated, and all subjects made serum IgG antibodies, predominantly IgG1, against L2E7. Nineteen of 25 tested persons made antigen-specific T cell proliferative responses to L2E7, and peripheral blood mononuclear cells when cultured with L2E7 in vitro produced both interferon-gamma and interleukin (IL)-5, although IL-5 predominated after the final vaccination. Five subjects completely cleared warts within 8 weeks. Subjects whose warts were not cleared by 8 weeks were offered conventional therapy. Recurrence of warts was not seen in any of the 13 persons whose warts cleared by vaccine alone or with conventional therapy. While these preliminary results of the use of this therapeutic immunogen are encouraging, proof of efficacy will require randomized double-blind trials.

Enhanced immunogenicity of a recombinant genital warts vaccine adjuvanted with monophosphoryl lipid A.

The regression of genital warts is believed to be a T-cell-mediated immune effect. We have sought to enhance the immunogenicity of a therapeutic vaccine for the treatment of genital warts with the use of the adjuvant monophosphoryl lipid A (MPL-immunostimulant), a detoxified form of the lipopolysaccharide (LPS) of Salmonella minnesota R595. The comparative immunogenicity and reactogenicity of a recombinant human papillomavirus type 6 (HPV6) L2E7 fusion protein in either aqueous, oil-in-water emulsions or Alhydrogel formulations containing MPL was evaluated. We conclude that the simple addition of MPL to the L2E7 fusion protein already adsorbed onto Alhydrogel preferentially enhances antigen specific in vitro T-cell proliferative responses, IFN gamma production and in vivo delayed type hypersensitivity responses without increasing its reactogenicity.

The impact of cardiology on the collective effective dose in the North of England.

Two cardiology X-ray rooms were monitored with dose-area product meters as part of a Regional Patient Dosimetry Programme. Dose-area product measurements on over 2000 patients undergoing examinations in the cardiology rooms are presented. The data have been corrected according to patient size where possible. In room A mean dose-area product values for coronary angiography, coronary angioplasty, radiofrequency ablation and mitral valvuloplasty were found to be 47.7, 72.2, 91.1 and 161.9 Gy cm2 respectively. In room B mean dose-area product values for coronary angiography and coronary angioplasty were found to be 23.4 and 51.6 Gy cm2 respectively. Observational studies were used to deduce the typical projections and technique factors. This typical examination was used to simulate an angiogram from which it was possible to derive factors to convert measured dose-area product values into estimates of effective dose. In room A, the effective doses were estimated to be 9.4, 14.2, 17.3 and 29.3 mSv for coronary angiography, coronary angioplasty, radiofrequency ablation and mitral valvuloplasty, respectively. The effective doses during coronary angiography and coronary angioplasty, performed in room B, were found to be 4.6 and 10.2 mSv, respectively. A regional survey of the frequency of these cardiac procedures was performed. It was deduced that the annual collective effective dose from these cardiac procedures in the North of England, the former Northern Region, was 45.7 manSv.

Shattered assumptions: time and the experience of long-term HIV positivity.

This paper elucidates one of the main existential problems faced by people living with an HIV positive diagnosis-the disruption in their routine orientation towards time and the way in which this has the capacity to affect their lives more generally. Drawing upon research with people who have been living with an HIV positive diagnosis for at least five years, the paper aims to illuminate the "provisional existence" imposed upon the individual by the diagnosis and suggests that this ambiguous position underpins the many psychological and social problems confronted by them. In addition, however, the paper argues that in order for the individual to adjust effectively to living with an HIV positive diagnosis, it is necessary for him/her to develop alternative ways of conceiving and living within time, which "compensates" for the loss of the temporal assumptions that existed prior to diagnosis. The various ways in which individuals manage to do this are documented in this paper, as is the failure to do so and the psychosocial consequences ensuing from this. It is further argued that the ability to achieve compensatory temporal understanding is related to the individual's more general "existential orientational framework", of which temporal perspective is a constituent component. Finally, the implications of such findings are discussed for the targeting of appropriate intervention strategies.

Hemlock: murder before the Lord.

Two healthy young men were killed by a plume of hemlock (Conium maculatum) emitted when contaminated incense was vaporized during religious rites about the middle of the thirteenth century BC.

Computed tomographic scanning of the lung in patients with allergic bronchopulmonary aspergillosis and in asthmatic patients with a positive skin test to Aspergillus fumigatus.

BACKGROUND: Allergic bronchopulmonary aspergillosis is a disease of asthmatic patients which may follow a protracted course and result in chronic lung damage such as central bronchiectasis. In asthma uncomplicated by allergic bronchopulmonary aspergillosis, in particular in asthmatic patients with immediate hypersensitivity type skin reactions to Aspergillus fumigatus, the incidence of bronchiectasis is uncertain. METHODS: Computed tomographic (CT) scans were performed in 17 asthmatic patients of mean (SE) age 60.1 (2.5) years, FEV1 49.4 (5.8)% predicted with allergic bronchopulmonary aspergillosis (all with current or previous positive precipitins to A fumigatus) and in 11 asthmatic patients of mean (SE) age 49.5 (5.8) years, FEV1 75.5 (6.5)% predicted, skin test positive for A fumigatus, but without the clinical or serological features of allergic bronchopulmonary aspergillosis (non-allergic bronchopulmonary aspergillosis group). RESULTS: Bronchial dilatation was more common in the group with allergic bronchopulmonary aspergillosis, affecting 14 patients compared with two in the non-allergic bronchopulmonary aspergillosis group. Evidence of bronchiectasis was found in 43 of a possible 102 lobes of patients with allergic bronchopulmonary aspergillosis, compared with three of a possible 66 in the non-allergic bronchopulmonary aspergillosis group. Bronchial wall thickening was common to both, affecting 16 and nine patients respectively. Pleural thickening on CT scanning was common in the group with allergic bronchopulmonary aspergillosis, being noted in 14 patients compared with only three in the non-allergic bronchopulmonary aspergillosis group. CONCLUSIONS: Bronchiectasis is common in allergic bronchopulmonary aspergillosis but occurs only occasionally in asthmatic patients with a positive skin test to A fumigatus but without other features of the disease.

Polymer membranes in clinical sensor applications. I. An overview of membrane function.

Polymer membranes are used in a wide variety of molecular sensing devices many of which are of potential clinical interest. The role of the polymer and the physical properties required of it are, however, rarely clearly defined. An extensive review is presented of the range of polymers whose use as membranes is described in the sensor literature. This forms the basis of an overview of membrane function in potentiometric amperometric and fibre optic sensors. In particular, the interaction of permeability, permselectivity and transmembrane potential is highlighted, together with the role of polymer membranes as matrices for the immobilization of reactive chemical and biological agents.

Polymer membranes in clinical sensor applications. III. Hydrogels as reactive matrix membranes in fibre optic sensors.

The potential of hydrogel copolymer membranes in clinical sensors, based on fibre optics, is addressed. The particular properties of the membranes of relevance in this application are the ease of refractive index modulation and the potential of the hydrogel to act as a permselective barrier in which a colorimetric agent may be immobilized. The results presented illustrate the complexity of colorimetric and refractive index effects together with their dependence on pH and tonicity for hydrogels of a given composition range. The incorporation of an acryloyl-functionalized reagent (bromopyrogallol red) is used to illustrate the way in which a working pH sensor based on these combined properties may be designed and fabricated.

Polymer membranes in clinical sensor applications. II. The design and fabrication of permselective hydrogels for electrochemical devices.

Hydrogels, particularly the tough, low water content materials, have potential advantages in the field of clinical biosensors because of their established use as medical polymers. The factors that control transport behaviour in these polymers are discussed with particular reference to ion selectivity. The nature of the transport behaviour in relation to coated wire electrode performance is presented and an extension of these permselectivity studies to the fabrication of miniaturized devices, such as ISFETs, is described. Linear soluble hydrogel polymers, coated on to sensor substrates, may be converted to insoluble membranes using solid photosensitive aromatic monomers, such as N-vinyl carbazole. Photolithographic patterning is achieved using a UV source together with appropriate masking, followed by an oxygen plasma etch process. Gas plasma etching, which selectively removes uncross-linked (masked) areas forms the basis of an all dry, low-temperature patterning process capable of giving micrometre-scale resolution. This novel photographic process, which does not damage or extract enzymes or ionophores, can advantageously be extended to the fabrication of poly(vinylchloride)-based membranes.

Fibrous dysplasia of the skull: disease activity in relation to age.

Eighteen of 19 patients with histologically confirmed fibrous dysplasia of the skull seen at the Institute of Neurological Sciences, Glasgow, in the past 20 years have been reviewed and recent radiographs obtained. Sex, age at presentation and at follow-up were recorded, in addition to the site, type and extent of cranial involvement. The findings have been related to disease activity and progression. In comparison with other reports we found the proportion of patients with activity in adulthood to be relatively high (37%). Overall, there was an equal sex distribution, but of seven patients presenting as adults, six were female as were six of seven patients with evidence of disease activity in adulthood.

Patient dose and associated risk due to radiological investigation of the internal auditory meatus.

The radiation doses and associated somatic risks due to four radiological examinations for acoustic neuromata (AN) have been investigated. These examinations were (1) plain film radiography of the internal auditory meatus (IAM), (2) computed tomography (CT) of the IAM, (3) CT of the posterior fossa and (4) CT of the IAM with air contrast. Organ dose measurements were performed using lithium fluoride thermoluminescent dosemeters loaded in a patient equivalent phantom. Dose equivalents to various organs are presented, together with the effective dose equivalent and collective effective dose equivalent for each examination. Hypothetical fatal somatic risks for each examination studied here have been estimated from the effective dose equivalents. The estimated number of hypothetical fatal cancers induced by radiological examinations for AN is between approximately 110 and 820 times lower than the number of detected AN, depending on the method of assessing the radiation dose to the remainder organs. It is concluded that in this particular study the radiological examinations are of net benefit to this group of patients.