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Aims: Pre-participation cardiovascular screening of young athletes may prevent sports-related sudden cardiac deaths. Recognition of physiological electrocardiography (ECG) changes in healthy athletes has improved the specificity of screening while maintaining sensitivity for disease. The study objective was to determine the clinical significance of electrocardiographic right ventricular hypertrophy (RVH) in athletes., Methods and Results: Between 2010 and 2012, 868 subjects aged 14-35 years (68.8% male) were assessed using ECG and echocardiography (athletes; n = 627, sedentary controls; n = 241). Results were compared against patients with established right ventricular (RV) pathology (arrhythmogenic right ventricular cardiomyopathy, n = 68; pulmonary hypertension, n = 30). Sokolow-Lyon RVH (R[V1]+S[V5orV6] > 1.05 mV) was more prevalent in athletes than controls (11.8 vs. 6.2%, P = 0.017), although RV wall thickness (RVWT) was similar (4.0 ± 1.0 vs. 3.9 ± 0.9 mm, P = 0.18). Athletes exhibiting electrocardiographic RVH were predominantly male (95.9%), and demonstrated similar RV dimensions and function to athletes with normal electrocardiograms (RVWT; 4.0 ± 1.1 vs. 4.0 ± 0.9 mm, P = 0.95, RV basal dimension; 42.7 ± 5.2 vs. 42.1 ± 5.9 mm, P = 0.43, RV fractional area change; 40.6 ± 7.6 vs. 42.2 ± 8.1%, P = 0.14). Sensitivity and specificity of Sokolow-Lyon RVH for echocardiographic RVH (>5 mm) were 14.3 and 88.2%, respectively. Further evaluation including cardiac magnetic resonance imaging did not diagnose right ventricular pathology in any athlete. None of the cardiomyopathic or pulmonary hypertensive patients exhibited voltage RVH without additional ECG abnormalities., Conclusion: Electrocardiographic voltage criteria for RVH are frequently fulfilled in healthy athletes without underlying RV pathology, and should not prompt further evaluation if observed in isolation. Recognition of this phenomenon should reduce the burden of investigations after pre-participation ECG screening without compromising sensitivity for disease.

Aims: This study was undertaken to determine the effectiveness of biological indicators currently being employed during formaldehyde decontamination. Data suggest that detectable amounts of formaldehyde are absorbed into the paper strips contained in currently used biological indicators. Absorbed formaldehyde has the potential to inhibit the growth of indicator spores, thus leading to false negative results. Indicators composed of either stainless steel carriers or paper strips were investigated to determine whether stainless steel carriers can be used as an alternative to paper strip indicators., Methods and Results: Biological indicators were exposed to formaldehyde gas and were tested for the presence of formaldehyde and any possible inhibition of spore growth. Absorbed formaldehyde was detected in the paper strip carriers while no formaldehyde was detected from any of the stainless steel carriers. Exposed paper strips were found to inhibit growth of up to 1 × 10(6) spores while the stainless steel carriers did not inhibit the growth of spores., Conclusions: During decontamination, biological indicators composed of paper spore strips absorb formaldehyde and inhibit growth of any surviving spores. Stainless steel carriers do not absorb formaldehyde and are an ideal alternative substrate for biological indicators., Significance and Impact of the Study: The popular paper strip biological indicator can lead to false negative results during decontamination and is unsuitable for validating formaldehyde decontamination., (© 2010 The Authors. Journal of Applied Microbiology © 2010 The Society for Applied Microbiology.)

Endobronchial interventions including the deployment of endobronchial stents have a clear role in the management of central airway problems. The use of endobronchial stents has rapidly increased since the first airway stent was developed in the 1960s and with the subsequent manufacture of improved silicone and metallic stents. They provide effective relief for symptoms of intrinsic and extrinsic airway obstruction secondary to a wide range of pathologies including lung cancer, lymphoma, thyroid carcinoma and benign disease such as tracheal strictures and tracheobronchomalacia. Endobronchial stents can also seal defects within the airway including malignant broncho-oesophageal fistulae and posterior wall tracheal tears. They can be placed safely under conscious sedation at flexible bronchoscopy or under general anaesthetic at rigid bronchoscopy. Rigid bronchoscopy under general anaesthesia provided by a multidisciplinary team is safe with few contraindications. Complications of endobronchial stents include infection, granulation tissue formation and metallic stent fracture sometimes requiring removal, although serious life-threatening complications are very rare. Increasing numbers of patients are being referred to specialist centres for airway intervention. This article reviews the history of endobronchial stents, the different stents available, and the indications, outcomes and complications involved in deploying endobronchial stents.

Objective: The purpose of this retrospective study is to review our experience with tacrolimus as a rescue immunosuppressant for heart transplant recipients with refractory rejection or cyclosporine intolerance., Methods: From June 1995 to November 1998, 15 cardiac transplant recipients were converted from our standard cyclosporine-based immunosuppressive regimen to a tacrolimus-based treatment. Each patient had been treated with cyclosporine, azathioprine and steroids. Six were switched to tacrolimus for persistent rejection, four for recurrent acute rejection and five for severe debilitating side-effects attributed to cyclosporine. All ten patients converted to tacrolimus because of rejection had been treated with high-dose methylprednisolone intravenously and four had also received anti-lymphocyte globulin (ALG; one patient) or anti-thymocyte globulin (ATG; three patients) preparations., Results: The time between transplantation and conversion to tacrolimus ranged from 44 to 1866 (median, 380) days. The range of follow-up after conversion was 84-1379 (median, 806) days. Eleven patients are alive with a follow-up period of 764+/-435 (median, 820) days. Four patients died between 90 and 930 (median, 464) days after conversion. The average number of episodes of acute rejection/recipient decreased from 2.1+/-1.6 on the cyclosporine regimen to 0.2+/-0.4 on the tacrolimus regimen (P<0.001). When the incidence of acute rejection was normalized for follow-up times (episodes/100 patient-days), the results were 1.1+/-1.4 and 0.07+/-0.2, respectively (P<0.01). The persistent/recurrent rejection resolved in all ten patients who were converted to tacrolimus. None of the five cyclosporine intolerant patients converted to tacrolimus experienced rejection after the changeover., Conclusions: In our experience, conversion from a cyclosporine-based to a tacrolimus-based maintenance immunosuppression has been shown to be an effective and safe approach to the management of patients with persistent or recurrent cardiac allograft rejection or those with cyclosporine intolerance.

Background: A proportion of heart transplant recipients develop poor graft function in the absence of cellular infiltrate in endomyocardial biopsies or transplant associated coronary artery disease. The condition has a poor prognosis and its aetiology is poorly understood. We report encouraging intermediate term results with total lymphoid irradiation (TLI) in the management of this condition., Methods: Eleven adult cardiac transplant recipients who developed severe allograft dysfunction (NYHA class-4) at a median period of 4 months after orthotopic heart transplantation were successfully treated with TLI. Endomyocardial biopsies and coronary angiography were normal in each patient and biventricular failure developed in spite of immunosuppression with Cyclosporin-A, Azathioprine, oral Prednisolone, Cyclophosphamide and intravenous Methylprednisolone therapy. Total lymphoid irradiation was given with standard Mantle and inverted Y-fields over ten treatments to achieve a cumulative dose of 8 Gy., Results: Each patient had a significant improvement in clinical response and in ventricular performance within 2 months of commencing TLI. Nine patients are currently well (four NHYA class-1, five NHYA class-2) at 4-48 (median 26) months following TLI. Two patients died; one from bacterial septicaemia and one as a consequence of chronic renal failure. Three patients developed opportunistic infection which was successfully treated with appropriate antimicrobial agents. An Ebstein-Barr virus associated lymphoproliferative disorder occurred in one patient and was successfully treated by reduction in immunosuppression and high dose Acyclovir. Two patients developed transient bone marrow suppression., Conclusion: The intermediate term results of TLI in the management of poor graft function in cardiac transplant recipients with normal endomyocardial biopsies and coronary angiography are encouraging. Although complications of opportunistic infection, bone marrow suppression and lymphoproliferative disorder occurred, treatment was successful in each case.

We have explored the potential antitumour activity of DNA-intercalating free radical generators based on compounds constructed from 9-anilinoacridine and chelidamic acid as an iron (II) binding centre. Here we describe their synthesis, DNA cleaving ability and activity against a panel of human tumour cell lines in culture. We also investigate their potential for use as DNA footprinting agents. Previous work has shown that the parent compound, FTP1, cleaves DNA in an essentially sequence neutral fashion and has modest cytotoxicity [Searcey, M., McClean, S., Madden, B. & Wakelin, L.P.G. (1997) Journal of the Chemical Society. Perkin Transactions, 2, 523]. Here we have equipped the acridine chromophore with an N,N-dimethylaminoethyl-4-carboxamide substituent, giving the threading agent FTP2, which confers selectivity for cleaving in GC-rich sequences, avoidance for binding to AT-tracts and 8-fold enhanced cytotoxicity compared with FTP1. Although this side chain bestows slow dissociation kinetics on DNA complexes of 9-anilinoacridines, it does not enhance the overall cutting efficiency of FTP2, implying that free-radical generation, DNA hydrogen abstraction and sugar fragmentation are fast compared with DNA-ligand complex lifetimes. FTP2 does not appear to be susceptible to resistance by the mdr phenotype in human ovarian carcinoma cells. We also report that FTP2 is an effective footprinting agent for GC-selective binding ligands and that it has some advantages over FTP1 in this regard.

Objective: Cytomegalovirus infection (CMV) is an important cause of morbidity and mortality following cardiac transplantation. The purpose of the present study was to ascertain whether routine post-operative screening for CMV infection influenced clinical management., Methods: Laboratory and case notes of 220 patients who received cardiac transplantation between November 1986 and October 1996 were reviewed. The range of follow-up was one to 120 (median 36) months. CMV surveillance involved blood tests for early antigen detection weekly for the first 6 post-operative weeks, fortnightly thereafter until the end of the third post-operative month and every 6 weeks to the end of the first post-operative year. Otherwise monitoring was performed if the patients had clinical symptoms suggestive of CMV infection. CMV sero-negative IgG recipients (R) of sero-positive IgG donor (D) organs and/or blood products received hyper-immune gammaglobulin for the first three post-operative months. Four patient groups were noted, namely R+D+ (59 patients), R+D- (70 patients), R-D+ (35 patients) and R-D- (56 patients)., Results: CMV antigenaemia was present in 40% (89) of patients and 48% (43) of these patients developed clinical features of CMV infection and received ganciclovir therapy. The distribution of clinical CMV infection requiring treatment was 25% (9/35) in the R+D- group, 50% (16/32) in the R+D+ group and 85% (18/22) in the R-D+ group. None of the patients in the R-D- group developed CMV antigenaemia. Forty six (52%) patients who were CMV antigen positive but who did not develop symptoms were not treated with ganciclovir and have remained well., Conclusion: Our results suggest that routine screening for CMV following cardiac transplantation is unnecessary. Surveillance did not result in the instigation of treatment for CMV unless there were associated clinical features of CMV infection.

Objective: Airway obstruction due to an excessive growth of granulation tissue at the level of the anastomosis is an important complication following lung transplantation which requires early diagnosis and treatment. We report encouraging experience in the management of this condition using endobronchial Nd:YAG laser therapy., Methods: Four adult lung transplant recipients developed airway anastomotic obstruction secondary to granulation tissue formation at 9, 10, 32 and 32 days following bilateral sequential lung transplantation (2 patients), en bloc double lung transplantation (1 patient) and single lung transplantation (1 patient). The diameter of the airways at the level of the anastomoses was reduced by 75, 30, 60, 60, 50 and 90%, respectively. Endobronchial Nd:YAG laser was applied via a fiberoptic bronchoscope introduced through a rigid bronchoscope. The granulation tissue was visualised and resected with photocoagulation with the laser using between 1000-2000 J depending on the amount of tissue present. Necrotic tissue was removed with large forceps. If the obstruction extended to the orifice of a lobar bronchus resection was undertaken in a staged fashion., Results: Airway patency was fully restored at two anastomotic sites, and restored to 90% patency at two and 80 and 75% at one each, respectively. This was associated with a significant improvement in pulmonary function in 3 patients. One patient had a subsequent bougie dilatation of a stenotic area and 2 patients received an endobronchial stent for tracheo or broncho-malacia. One patient died from a gastrointestinal haemorrhage. Three patients are well at 10, 17 and 18 months following transplantation and have no further granulation tissue recurrence. There were no complications directly attributable to laser therapy., Conclusion: Our encouraging early experience leads us to suggest that Endobronchial Nd-YAG laser therapy should be considered in the management of airway anastomotic obstruction due to excessive granulation tissue formation after lung transplantation.

Macrophages separated from lavage samples obtained from lungs removed at transplantation from patients with cystic fibrosis (CF) and other lung diseases, have been compared with circulating monocytes from the same patients for their ability to stimulate allogeneic normal circulating lymphocytes and to present antigen to autologous hilar lymph node cells. In general, macrophages separated from lavage samples from CF patients were unable to stimulate allogeneic lymphocytes and to present antigen, although monocytes from the same patients were functional in both assays. In contrast, lavage cells from non-CF patients were generally effective in both allogeneic stimulation and antigen presentation. These data suggest that immune cells within the lungs of CF patients are functionally compromised, a deficiency which may contribute to the recurrent infections characteristic of the disease.

The QT responses to exercise during ventricular pacing were evaluated in 12 patients in whom permanent pacemakers were implanted for complete heart block. The initial response of the QT to exercise was a paradoxical lengthening during the first minute of exercise (mean 4.8 ms P < 0.01). Thereafter, the QT was found to shorten in a linear fashion in response to increasing exercise, both in terms of exercise duration (r = 0.787; P < 0.001) and atrial rate (r = 0.712; P < 0.001). The total QT shortening with exercise was small (20 ms for a mean increase in atrial rate of 60 beats.min-1) and displayed substantial inter-individual variability (9-31 ms). These results explain some of the limitations of the QT pacemaker, and provide insights in to the dynamics of the QT response, which may help tailor the programming of these systems to the individual patient.

A 35-year-old man developed giant cell myocarditis resulting in severe congestive cardiac failure. He needed urgent orthotopic cardiac transplantation despite maximal doses of inotropes and augmentation with an intra-aortic balloon pump. The patient presented with rhythm disturbances and echocardiographically diminished ventricular function at subsequent follow-up. Biopsies then taken revealed recurrence of myocarditis in the transplanted heart. Investigations revealed no obvious cause for the myocardial granulomas nor any evidence of systemic granulomatous disease. The patient received, in addition to maintenance cyclosporin A and azathioprine, high doses of corticosteroids which resulted in complete resolution of the inflammatory process and no recurrence has been detected to date. This case shows that giant cell myocarditis can recur in the transplanted heart despite routine immunosuppression with azathioprine and cyclosporin A and that additional treatment with high dose corticosteroids is effective in causing regression of the inflammatory process.

Eight monoclonal antibodies, specific for the glycoprotein hormone alpha-subunit, were raised against human free alpha-subunit, human FSH, or human CG. All of these antihuman monoclonal antibodies were tested for cross-reactivity with alpha-subunits derived from bovine, porcine, equine, bull frog, sea turtle, turkey, and ostrich glycoprotein hormones. All showed cross-reactivity with affinities ranging from 10(-4) to 10(-8) depending upon the antibody and the species of alpha-subunit. Cyanogen bromide fragments of bovine and equine alpha, when tested with selected antibodies indicated that antigenic determinants could be localized in two regions: alpha 9-33 and alpha 76-92. Comparison of amino acid sequences, and relative potencies, suggest that major antigenic determinants involve residues 21, 22, and 23 (F-F-S in human alpha) and 76-85 (G-G-F-K-V-E-N-H-T-A in human alpha). As part of this study the N-terminal amino acid sequences of bull frog, sea turtle, turkey, and ostrich alpha-subunits were determined and reported for the first time.

Between 1979 and 1985, seven patients (five children and two adults) were treated for primary cardiac tumours other than benign atrial myxomas. There were five malignant neoplasms (two non-classifiable sarcomas, one haemangiosarcoma, one histiocytoma and one neurofibrosarcoma) and two benign tumours (fibromas). Echocardiography, cardiac catheterisation, computed tomography and magnetic resonance imaging provided diagnostic confirmation. The two patients with fibroma are alive and well 4 and 5 years after radical resection of the tumours from the interventricular septum. The patient with a neurofibrosarcoma underwent orthotopic cardiac transplantation and is well 5.5 years postoperatively with no evidence of residual disease or recurrence. One patient died awaiting a donor heart for transplantation. Another patient who was a candidate for heart and lung transplantation was found to have an unresectable tumour at the time of operation. One patient with sarcoma who underwent a successful emergency partial resection for relief of cardiac tamponade died 18 months later from widespread metastases. The seventh patient was inoperable due to multiple secondaries. It is concluded that radical resection of large, benign, cardiac tumours can give good results and that early cardiac transplantation probably offers the only hope for patients with malignant tumours of the heart.