Transthoracic echocardiography: a survey of current practice in the UK.

BACKGROUND: Echocardiography is one of the cornerstones of cardiovascular investigation. The escalating demands on echocardiography services necessitate close examination of how we organize our departments on a day-to-day basis, in order to provide a consistent, high-quality service. AIM: To evaluate current transthoracic echocardiography practice in the UK. DESIGN: National postal survey. METHODS: A questionnaire was sent to the chief cardiac physiologist (CP) of every hospital in the UK with echocardiographic facilities. RESULTS: Three hundred and thirty six echocardiographic departments were identified. One hundred and twenty six (37.5%) completed questionnaires were returned. In 87% of hospitals, CPs both performed and reported over 80% of echocardiograms. Fifty-seven percent of CPs and 22% of doctors performing echocardiography held an accreditation in echocardiography. Only 60% of hospitals had formal criteria that had to be met prior to an operator being allowed to report echocardiograms unsupervised. Fewer than half of hospitals regularly audited their echocardiography service. Both outpatient and inpatient waiting times for echocardiography were highly variable and frequently excessive. Fewer than half of hospitals used modern techniques for assessing diastolic function, mechanical dyssynchrony or severity of mitral regurgitation. CONCLUSION: In the UK, many transthoracic echocardiograms are performed and reported by operators without formally assessed competence. Fewer than half of hospitals regularly audited their service or used modern echocardiographic techniques. Services are likely to be improved by developing and instituting mandatory national guidelines.

Pericardiocentesis practice in the United Kingdom.

BACKGROUND: Pericardial effusions frequently present challenging clinical dilemmas. Whether or not to drain an effusion, and if so by what method, are two common decisions facing cardiologists. We performed a survey to evaluate pericardiocentesis practice in the United Kingdom (UK). METHODS: A total of 640 questionnaires were sent to all cardiologists in the UK Directory of Cardiology in March 2003. RESULTS: A total of 274 (43%) completed questionnaires were returned, 88% from consultants, equally distributed between tertiary referral centres and district general hospitals. More than 1500 procedures were performed, largely using a paraxiphoid approach (89%). Clinical tamponade was the commonest indication for pericardiocentesis (83%). However, the majority of respondents (69%) considered echocardiographic features alone an indication for pericardiocentesis, even in the absence of clinical tamponade. The commonest perceived indications for drainage were right ventricular diastolic collapse and right atrial collapse (69% and 33% of respondents respectively). For guidance, 82% use echocardiography, either alone or with fluoroscopy or the electrocardiogram (ECG) injury trace. 11% employ fluoroscopy alone or with the ECG injury trace. The remaining 11% stated that they would use the ECG injury trace alone or use no guidance. Using the ECG injury trace alone is said by the European Society of Cardiology (ESC) guidelines to offer an inadequate safeguard. Reported complications included ventricular puncture (n = 12, 0.8%) and hepatic damage (n = 4, 0.3%). CONCLUSION: Pericardiocentesis practice varies substantially in the UK. Many cardiologists would perform pericardiocentesis based on echocardiographic features alone. 11% of cardiologists use guidance that is considered inadequate by the ESC guidelines.

Genomics of antiviral defenses in the duck, a natural host of influenza and hepatitis B viruses.

We review our progress using genomics approaches to examine key antiviral defenses of the White Pekin mallard duck, Anas platyrhynchos. Our interest stems from the fact that ducks are the natural host of avian influenza, and are an important animal model for hepatitis B research. First, we have conducted an expressed sequence tag (EST) project and identified more than 200 immune relevant genes in the duck. Our analysis of these genes allows us to evaluate the homology between ducks and their closest genetic model organism, the chicken. We have also constructed genomic and cDNA libraries from the same individual duck, allowing us to directly compare expressed sequences with those present in the genome. These resources allow us to determine the organization and expression of regions of the genome important in antiviral defenses. Here we examine the organization of the immunoglobulin heavy chain locus, the Major Histocompatibility Complex class I region, the lectin immunoreceptors and Toll-like receptor 7. We discuss our research-in-progress in the context of the immune defense against viruses, particularly influenza.

Results of arthrodesis in neuropathic feet.

We describe the results of arthrodesis for the treatment of recurrent acute neuropathic bone disease in 24 feet and of chronic disease with deformity in 91 feet, undertaken between January 1984 and December 2003. All were due to leprosy. Correction of the deformity was achieved in 80 of 106 feet (76%) and fusion in 97 of 110 feet (88%). In the 24 feet in which recurrent neuropathic bone disease was the reason for surgery, 17 (71%) obtained stability while in seven (29%) symptoms recurred postoperatively. Complications were experienced following 58 of the 110 operations (53%). In patients presenting primarily with deformity with a minimum follow-up of two years (79 feet), there was a reduced frequency of ulceration in 40 (51%). Normal footwear could be worn by 32 patients (40%) after surgery, while 40 (51%) required a moulded insole. Arthrodesis of the ankle in the neuropathic foot due to leprosy has a good overall rate of success although the rate of complications is high.

Sindbis virus translation is inhibited by a PKR/RNase L-independent effector induced by alpha/beta interferon priming of dendritic cells.

The tropism of Sindbis virus (SB) for cells of the dendritic cell (DC) lineage and the virulence of SB in vivo are largely determined by the efficacy of alpha/beta interferon (IFN-alpha/beta)-mediated antiviral responses. These responses are essentially intact in the absence of PKR and/or RNase L (K. D. Ryman, L. J. White, R. E. Johnston, and W. B. Klimstra, Viral Immunol. 15:53-76, 2002). In the present studies, we investigated the nature of antiviral effects and identity of antiviral effectors primed by IFN-alpha/beta treatment of bone marrow-derived DCs (BMDCs) generated from mice deficient in PKR and RNase L (TD). IFN-alpha/beta priming exerted significant antiviral activity at very early stages of SB replication and most likely inhibited the initial translation of infecting genomes. The early effect targeted cap-dependent translation as protein synthesis from an SB-like and a simple RNA were inhibited by interferon treatment, but an encephalomyocarditis virus internal ribosome entry site-driven element exhibited no inhibition. Phosphorylation of the alpha subunit of eukaryotic translation initiation factor 2 was defective after virus infection of TD cells, suggesting other mechanisms of translation inhibition. To identify components of these alternative antiviral pathway(s), we have compared global gene regulation in BMDCs derived from normal 129 Sv/Ev, IFNAR1-/-, and TD mice following infection with SB or treatment with IFN-alpha/beta. Candidate effectors of alternative antiviral pathways were those genes induced by virus infection or IFN-alpha/beta treatment in 129 Sv/Ev and TD-derived BMDC but not in virus-infected or IFN-alpha/beta-treated IFNAR1-/- cells. Statistical analyses of gene array data identified 44 genes that met these criteria which are discussed.

Spliced mRNA encoding the murine cytomegalovirus chemokine homolog predicts a beta chemokine of novel structure.

A viral mRNA of the late kinetic class expressed by murine cytomegalovirus (MCMV) contains an open reading frame (ORF) whose predicted protein, designated MCK-1, has homology to beta chemokines (M. R. MacDonald, X.-Y. Li, and H. W. Virgin IV, J. Virol. 71:1671-1678, 1997). The present study analyzed further the structure of the transcript in infected fibroblast cells. A splicing event removed the MCK-1 stop codon, bringing a downstream ORF into frame with the chemokine homolog and demonstrating that the MCK-1 ORF was an exon of a larger gene. The predicted 31.4-kDa protein, designated MCK-2, contains a putative amino-terminal signal sequence and a beta chemokine domain, followed by a carboxyl-terminal domain without significant homology to known proteins. Quantitative analysis of mRNA forms in MCMV-infected fibroblast cells at late times after infection indicated that the viral chemokine RNA was predominantly spliced. There was no evidence for expression of RNA encoding either MCK-1 or MCK-2 at immediate early or early times after infection with MCMV. Monoclonal antibodies generated against bacterially expressed MCK-2 recognized multiple proteins in the range of approximately 30 to approximately 45 kDa in Western blot analysis of MCK-2 expressed in transfected COS cells. The monoclonal antibodies immunoprecipitated a similar group of proteins in transfected COS cells metabolically labeled with radioactive cysteine. Radiolabelled protein of apparent higher molecular mass was immunoprecipitated from culture medium overlying the transfected cells, suggesting that posttranslationally modified MCK-2 can be secreted. Two proteins with apparent molecular mass suggestive of posttranslational modification were detected by Western blot analysis of cells harvested at late times after infection with MCMV. These studies show that MCMV encodes and expresses a beta chemokine homolog with a novel predicted structure.

An anatomical approach to glabellar rhytids.

OBJECTIVE: To identify surface landmarks that can serve as reference points to the underlying musculature in the treatment of glabellar rhytids. METHODS: Fifty cadaver hemibrows were dissected to assess the location, disposition, and relationships of the brow muscles, along with their variations at each of several consistent locations. Particular attention was paid to the corrugator supercilii, frontal belly of the frontalis, and procerus muscles. CONCLUSIONS: The information gained here may be applied to the pharmacological or surgical treatment of glabellar rhytids. Knowledge of the frequent location of the muscles involved, relative to easily identifiable surface landmarks, allows a more precise approach.

Mucosal and parenteral vaccination against acute and latent murine cytomegalovirus (MCMV) infection by using an attenuated MCMV mutant.

We used a live attenuated murine cytomegalovirus (MCMV) mutant to analyze mechanisms of vaccination against acute and latent CMV infection. We selected MCMV mutant RV7 as a vaccine candidate since this virus grows well in tissue culture but is profoundly attenuated for growth in normal and severe combined immunodeficient (SCID) mice (V. J. Cavanaugh et al., J. Virol. 70:1365-1374, 1996). BALB/c mice were immunized twice (0 and 14 days) subcutaneously (s.c.) with tissue culture-passaged RV7 and then challenged with salivary gland-passaged wild-type MCMV (sgMCMV) intraperitoneally (i.p.) on day 28. RV7 vaccination protected mice against challenge with 10(5) PFU of sgMCMV, a dose that killed 100% of mock-vaccinated mice. RV7 vaccination reduced MCMV replication 100- to 500-fold in the spleen between 1 and 8 days after challenge. We used the capacity to control replication of MCMV in the spleen 4 days after challenge as a surrogate for protection. Protection was antigen specific and required both live RV7 and antigen-specific lymphocytes. Interestingly, RV7 was effective when administered s.c., i.p., perorally, intranasally, and intragastrically, demonstrating that attenuated CMV applied to mucosal surfaces can elicit protection against parenteral virus challenge. B cells and immunoglobulin G were not essential for RV7-induced immunity since B-cell-deficient mice were effectively vaccinated by RV7. CD8 T cells, but not CD4 T cells, were critical for RV7-induced protection. Depletion of CD8 T cells by passive transfer of monoclonal anti-CD8 (but not anti-CD4) antibody abrogated RV7-mediated protection, and RV7 vaccination was less efficient in CD8 T-cell-deficient mice with a targeted mutation in the beta2-microglobulin gene. Although gamma interferon is important for innate resistance to MCMV, it was not essential for RV7 vaccination since gamma interferon receptor-deficient mice were protected by RV7 vaccination. Establishment of and/or reactivation from latency by sgMCMV was decreased by RV7 vaccination, as measured by diminished reactivation of MCMV from splenic explants. We found no evidence for establishment of splenic latency by RV7 after s.c. vaccination. We conclude that RV7 administered through both systemic and mucosal routes is an effective vaccine against MCMV infection. It may be possible to design human CMV vaccines with similar properties.

Late expression of a beta chemokine homolog by murine cytomegalovirus.

A gene (HJ1) present in murine cytomegalovirus (MCMV) encodes an open reading frame (ORF) whose predicted amino acid sequence shows homology to the beta (or C-C) class of chemotactic cytokines known as chemokines. The region of homology is located in the carboxyl-terminal portion of the 116-amino-acid ORF. A 0.9-kb RNA transcript corresponding to the HJ1 gene is expressed in MCMV-infected fibroblasts and macrophages as a member of the late kinetic class of virally encoded transcripts. A transcriptional start site is located between the third and fourth methionine residues in the ORF, predicting a primary amino acid structure, starting at the fourth methionine residue, which includes a possible signal peptide as well as conserved cysteine residues typical for mammalian beta chemokines. The RNA transcript is polyadenylated, suggesting that it can undergo translation within the cytoplasm of an MCMV-infected cell. We speculate that expression of the chemokine homolog at late times in the MCMV replication cycle plays a role in MCMV pathogenesis, possibly by action as a chemotactic agonist or antagonist or by alteration of the activation or differentiation state of a susceptible cell such as a macrophage.

Marshall-Stickler phenotype associated with von Willebrand disease.

We report on 6 individuals from three different kindreds with Marshall-Stickler (MS) phenotype, with characteristic orofacial abnormalities, arthropathy, deafness, and eye findings, all of whom were discovered to have a mild bleeding diathesis and coagulation-study findings consistent with mild von Willebrand disease (vWD). MS syndrome has been linked in some cases to the type II procollagen gene (COL2A1) on chromosome 12q, and to the collagen XI gene (COL11A2) on chromosome 6. The von Willebrand factor (vWF) is encoded by a 180-Kb gene located on the short arm of chromosome 12. This is the first reported association of these two disorders.

Wide polytef (Gore-Tex) implants in lip augmentation and nasolabial groove correction.

OBJECTIVE: To describe a new technique of polytef (Gore-Tex) implantation into the upper and lower lips and nasolabial grooves by using large implants as a method that achieves effective cosmetic improvement. SETTING: A private cosmetic surgery center. PARTICIPANTS: Thirty-three (female) patients who desired fuller lips and 62 patients (52 female and 10 male) who requested less prominent cheek lip grooves. MAIN OUTCOME MEASURE: Significant patient satisfaction after 12 to 54 months. RESULTS: Conspicuous aesthetic effect that related to both lip and nasolabial groove correction was documented. All patients but 4 (2 in each group) were pleased with the final outcome of the treatment. CONCLUSIONS: In the opinion of the authors, the threading technique of polytef implantation creates inconspicuous improvement-both in lip augmentation and nasolabial groove correction. Large polytef implants that were inserted through a tunneling technique produced consistently good results. Implants (lip augmentation: width, < or = 10 mm, and thickness, 4 mm; nasolabial groove correction: width, 8 mm, and thickness, < or = 8 mm) were found to be safe, simple, and effective.

Murine cytomegalovirus with a deletion of genes spanning HindIII-J and -I displays altered cell and tissue tropism.

Murine cytomegalovirus (MCMV) gene products dispensable for growth in cell culture are likely to have important functions within the infected host, influencing tissue tropism, dissemination, or immunological responses against the virus. To identify such genes, our strategy was to delete large regions of the MCMV genome likely to contain genes nonessential for virus replication in NIH 3T3 cells. Mutant virus RV7 contained a deletion of 7.7 kb spanning portions of MCMV HindIII-J and -I. This virus grew comparably to wild-type (WT) virus in NIH 3T3 fibroblasts, primary embryo fibroblasts, and bone marrow macrophages. However, RV7 failed to replicate in target organs of immunocompetent BALB/c mice and severe combined immunodeficient mice, which are exquisitely sensitive to MCMV infection. This defect in vivo growth may be related to the observation that RV7 grew poorly in the peritoneal macrophage cell line IC-21, which is highly permissive for growth of WT MCMV. Two other mutant viruses with an insertion or smaller deletion in the region common to the RV7 deletion grew comparably to WT virus in the macrophage cell line and replicated in salivary gland tissue. The poor growth of RV7 in IC-21 cells was due to a block in immediate-early gene expression, as levels of RNA from immediate-early gene IE1 were reduced eightfold compared with levels for WT virus in macrophages infected with RV7. Consequently, levels of RNA from early and late genes were also reduced. The lower expression of IE1 in RV7-infected IC-21 macrophages was not due to defective entry of virus into the cells, as equal amounts of viral DNA were present in cells 3 h after infection with RV7 or WT MCMV. These studies demonstrate that deletion of sequences in HindIII-J and -I confer altered cell and tissue tropism.

Congenital cystic adenomatoid malformation of the lung referred as 'airway foreign body'.

Congenital cystic adenomatoid malformation of the lung is an uncommon anomaly. Two patients with this condition were recently referred to the Otolaryngology Service at The Hospital for Sick Children, Toronto, Ontario, for bronchoscopic evaluation of the airway to rule out a foreign body. Although history did not disclose a clear episode of aspiration in either case, chest radiographs showed unilateral lobar hyperinflation with mediastinal shift, consistent with foreign body obstruction. We report two cases to introduce congenital cystic adenomatoid malformation to the English otolaryngology literature and to increase awareness of it among otolaryngologists.