Does adherence to universal precautions correlate with the prevalence of blood-borne infections?
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Biomedical subjects
Publications and source records attributed to J Breuer.
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AIM: To investigate the role of human papillomavirus (HPV) in the development of bladder transitional cell carcinoma (TCC). METHODS: Seventy eight paraffin wax embedded TCC samples were tested for the presence of HPV by two methods. First, immunohistochemistry was carried out using a polyclonal antibody capable of detecting the capsid protein of all known papillomaviruses. The second method was a consensus GP5+/6+ primer mediated polymerase chain reaction (PCR) technique, with the products analysed by both agarose gel electrophoresis and an enzyme immunoassay using type specific oligonucleotide probes for 10 different mucosal genotypes. To exclude false negative results because of the poor quality of DNA extracted from paraffin wax embedded samples, the series was extended to include 20 further blocks for which the corresponding snap frozen unfixed tissue was available. RESULTS: The two methods produced contrasting results, with 47 of the 78 samples positive for HPV antigen and none positive for HPV DNA. HPV DNA was not detected in the 20 additional paraffin wax embedded TCCs or in the 20 paired unfixed samples. In contrast, HPV DNA was amplified by PCR from all six of the paraffin wax embedded cervical carcinoma and anogenital wart control samples. CONCLUSION: The disparity between the two sets of results is probably caused by false positives resulting from the non-specificity of the polyclonal antibody used for immunohistochemistry. These results suggest that HPV is unlikely to play an aetiological role in the development of bladder TCC.
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BACKGROUND: Human papillomaviruses (HPVs) are found in normal skin and in benign and malignant skin conditions. Epidermodysplasia verruciformis (EV) HPV types are those most plausibly linked to the development of squamous cell carcinomas of the skin. OBJECTIVES: To assess the risk of nonmelanoma skin cancer (NMSC) associated with the presence of EV HPV in normal skin in immunocompetent (IC) individuals and renal transplant recipients (RTRs). METHODS: Using a degenerate and nested polymerase chain reaction technique, HPV DNA was sought in 124 normal skin samples from sun-exposed and nonsun-exposed sites, from 39 IC individuals and 38 RTRs, both with and without NMSC. Data were analysed using the Mantel-Haenszel test and by logistic regression analysis. RESULTS: HPV DNA was detected in 58/67 (87%) and 20/57 (35%) samples from renal transplant and IC patients, respectively. There was no difference in either the prevalence or spectrum of HPV types found in sun-exposed and nonsun-exposed normal skin. However, there was significant association between NMSC and the presence of EV HPV DNA. Multivariate analysis provided an odds ratio of 6.41 (95% confidence interval 1.79-22.9) for the association of EV HPV DNA in normal skin (irrespective of site) and NMSC status, even after stratifying for patient group and adjusting for the clustering effect of multiple sampling. Conversely, there was no association between skin cancer status and the presence of cutaneous or mucosal HPV types in either sun-exposed or nonsun-exposed skin. CONCLUSIONS: HPV DNA is widespread in normal adult skin, particularly in transplant patients. In our study, the presence of EV but not cutaneous HPV DNA in normal skin was significantly associated with NMSC status and may prove to be of predictive value for skin cancer risk. These data provide reason to focus on EV HPV types as causal agents in skin cancer.
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Heteroduplex mobility assay was used to identify variants of varicella-zoster virus (VZV) circulating in the United Kingdom and elsewhere. Forty variable positions were identified. Sixteen substitutions were non-synonymous, resulting in an amino acid change, the majority of which were clustered within surface expressed proteins. Phylogenetic analysis distinguished at least three major clades (strains A, B, C) supported by significant bootstrap values. Apart from the United Kingdom and Brazil where all three strains were found, genotypes appeared to be closely associated with the geographical region in which they were sampled. Allelic co-segregation of widely spaced single nucleotide polymorphisms (SNPs) confirmed the genetic stability of the VZV. Recombination rates were difficult to calculate because of the low intra genotypic variation. However, one haplotype originating from Brazil is most parsimoniously explained as a recombinant between A and C strains, which co-occur in the region. Two further UK strains appeared to be recombinants between groups B and C.
OBJECTIVE: To evaluate the clinical feasibility of conventional cardiotocography (CTG) as a cardiac cycle triggering signal for three-dimensional (3D) fetal echocardiography. METHOD: Free-hand 3D echocardiography was performed on a total of 25 fetuses with and without congenital heart disease at various gestational ages (mean, 29 weeks; range, 19-35 weeks). Simultaneously, online CTG was used for time gating. Gray-scale and color Doppler dynamic 3D displays, as well as multiplanar views, were assessed for their ability to depict the cardiac morphology and correct cardiac gating. RESULTS: Valid CTG-based trigger signals could be obtained in 24 of the 25 fetuses. Correct cardiac gating was achieved in 101 of the 111 (91%) 3D datasets. Color Doppler imaging of blood flow in four dimensions was possible in 34 of 36 (94%) datasets. Reconstructed 3D and multiplanar views provided additional views not available in two-dimensional (2D) imaging. Acoustic interference between the CTG transducer and echotransducer could be reduced by the use of a high-frequency echotransducer, second-harmonic frequency imaging and appropriate positioning of the two transducers. Imaging quality was highly dependent on the quality of 2D images and random motion artifacts. CONCLUSIONS: CTG can be used as an online gating source for dynamic 3D fetal echocardiography.
The genome of varicella-zoster virus (VZV) contains nearly 125,000 bp. Preliminary genomic analysis has revealed that VZV may be less immutable than once thought. Through the investigation of the VZV genome using specifically designed oligonucleotides, it has been learned that sequence variation within VZV open reading frame 62 can distinguish between vaccine and wild-type virus. Additionally, the presence of single nucleotide polymorphisms within the VZV genome has identified distinct VZV populations originating from circumscribed geographic locations. In order for future studies of VZV genetic diversity to be carried out, amplifying and sequencing primers for individual VZV genes have been catalogued. Additionally, this report will facilitate the selection of VZV primers by which to distinguish clinical VZV isolates from vaccinia virus isolates.
Varicella zoster virus (VZV) is a stable virus showing relatively little variation. Nevertheless, recent data have shown there to be at least four distinct viral strains. For the most part these are geographically segregated, but in areas of the world such as the UK, where mixed populations live, there is evidence for spread of all the genotypes. Little is known about the biological differences, if any, between these strains, yet recent data have shown that even a single nucleic acid change can affect the biological behaviour of the virus. The Oka vaccine has been licensed for mass vaccination in the US and for limited use in the UK, particularly in seronegative healthcare workers. Virological surveillance is needed to support these programmes and study the effect on virus spread. Evidence for VZV superinfection of latently infected individuals with different strains, and the increasing detection of VZV in association with clinical conditions such as viral meningitis, suggest more data are needed on the transmissibility and biological properties of the virus.
This study was performed in order to assess the potentially different effects of the angiotensin-converting enzyme inhibitor captopril and of the angiotensin II receptor antagonist irbesartan on the metabolic syndrome in an animal model. Male NZO/BL6 F1 mice were treated with captopril, irbesartan, or placebo for 10 months: Control animals treated with placebo developed a metabolic syndrome with obesity (55.5+/-6.3 g), hypertension (146+/-10 mm Hg), hyperinsulinemia (7.2+/-5.7 ng/ml), hypercholesterolemia (5.1+/-0.7 mmol/l), cardiac hypertrophy (269+/-44 mg) and atherosclerotic plaques in the ascending aorta (3.6+/-1.5 microm(2)). Treatment with angiotensin-converting enzyme inhibitor or angiotensin II receptor antagonist significantly (p<0.001) reduces hypertension (73+/-5 and 78+/-11 mm Hg), cardiac hypertrophy (203+/-26 and 202+/-18 mg) and atherosclerosis (2.2+/-0.9 and 1.8+/-0.8 microm(2)). In addition, they prevented the development of obesity (42.2+/-3.5 and 38.3+/-2.8 g) and hyperinsulinemia (3.6+/-1.5 and 1.8+/-0.4 ng/ml). In conclusion, long-term treatment with an angiotensin-converting enzyme inhibitor or an angiotensin II receptor antagonist can ameliorate obesity and hyperinsulinemia in a genetically determined mouse model.
A 45 year old male suffered from typical exercise-induced dyspnoea and angina. Crohn's disease treated with glucocorticoids was present for 18 years. Coronary angiography revealed small left anterior descending and right coronary arteries without reference to coronary artery disease, while the main stem and circumflex artery were severely dilated due to a fistula (diameter 5.5 mm) into the coronary sinus with a left/right shunt amounting to 35%. Haemodynamics, significant risk of endocarditis with chronic inflammatory bowel disease and obligatory glucocorticoid treatment were indications for fistula closure. As an alternative to surgical correction, the coronary fistula was totally occluded by antegrade micro-coil embolization. The present report offers a review on differential therapeutic considerations and specific treatment options including novel interventional modalities for coronary fistulas.
A growing number of antiviral agents are available for treatment of persistent viral infections. This has increased the requirement for virology laboratories to undertake sophisticated assays for monitoring the efficacy of treatment and identifying drug failure at an early stage. The consensus guidelines within this article address the laboratory requirements for monitoring treatment of the herpes viruses, HIV-1, Hepatitis B and Hepatitis C.
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Heteroduplex mobility assays of 37 regions were performed on ten UK isolates of varicella zoster virus, four from cases of zoster, and six from cases of chickenpox. The variation between isolates was found to be 0.061%, which is at least five times lower than any other member of the human herpesvirus family. Fifteen of the 37 regions tested had 29 single nucleotide polymorphisms, and over half the polymorphisms were located in four gene fragments. Of the 29 SNPs, eleven were non-synonymous and these were clustered in six genes. Isolates from a child and her mother to whom she had transmitted the virus, were identical at every locus tested. All other viruses could be distinguished by a combination of SNPs and length polymorphisms of the repeat regions R1, R2 and R5.
The amounts of calcium and strontium were measured by inductively coupled plasma mass spectrometry (ICP-MS) in saccular and utricular inner ear otoliths (sagittae and lapilli, respectively) of developing cichlid fish. These fish had been maintained for 22 days at 3-g hypergravity conditions within a centrifuge. During this time-span, the animals completed their ontogenetic development from hatch to the free-swimming stage. Neither the morphogenetic development nor the timely onset and gain of performance of the swimming behaviour was impaired by the experimental conditions. Experimental and control animals also did not differ concerning their size (total length). ICP-MS revealed that the otoliths contained significantly less calcium (in microg/otolith) after hyper-g exposure compared to parallelly raised 1-g control specimens (lapilli: 0.74+/-0.21 vs. 1.16+/-0.41; sagittae: 2.09+/-0.49 vs. 2.76+/-0.47). The content of strontium (in microg/otolith: lapilli: 0.0044+/-0.0023 vs. 0.0022+/-0.0013; sagittae: 0.0094+/-0.0026 vs. 0.0081+/-0.0016) and, consequently, the Sr/Ca ratio (Sr/Cax100) was increased (lapilli: 0.607+/-0.267 vs. 0.201+/-0.12; sagittae: 0.439+/-0.093 vs. 0.301+/-0.086). Since the calcium content can be taken as a proxy for otolith weight, and because parallelly undertaken morphometric investigations revealed smaller otoliths (maximum radius and surface area) due to hyper-g exposure, the results suggest that the growth of otoliths at hyper-g is slowed down. Since the concentration of trace elements incorporated into otoliths is likely based on the composition of the respective protein matrix, our findings suggest that the protein metabolism is affected by hypergravity.
OBJECTIVES: To evaluate clinical and RNA load response to antiretroviral therapy amongst patients infected with HIV-2 and to study the development of drug resistance. METHODS: Seven HIV-2 seropositive patients were monitored with clinical examination, CD4 cell count and HIV-2 viral RNA load. Viruses from four subjects were genotyped and in vitro recovery of virus by co-cultivation with PBMCs and HVS T-cells was attempted. Viruses isolated from two subjects were assayed for phenotypic antiviral resistance. The main outcome measures were the relationship between disease stage, viral load, CD4 cell count, viral subtype and the clinical course of HIV-2 infection and the effect of combination antiretroviral therapy on disease progression, CD4 cell count, HIV-2 RNA viral load and drug resistance. RESULTS: The median time of follow-up was 3 years (range 0-8 years). Three patients had AIDS, and one had symptomatic disease. Of the four patients genotyped, three were infected with HIV-2 subtype B and one with subtype A. Viraemia was detectable only at CD4 counts of less than 300 x 10(6)/ml. Two patients with high viral loads failed to respond to antiretroviral therapy although their treatment may not have been optimal. One developed in vitro phenotypic antiviral resistance. The genotype of this patient's viral reverse transcriptase is being analysed. CONCLUSIONS: In contrast to HIV-1, HIV-2 RNA levels were often undetectable despite advanced disease and low CD4 cell counts. However, HIV-2 was clearly capable of causing CD4 cell depletion resulting in symptomatic disease. The principles of highly active antiretroviral therapy seem to apply to HIV-2 and suboptimal therapy may lead to drug resistance. The timing of therapy initiation, monitoring of response and the measurement of resistance remain unresolved issues and conclusions cannot be extrapolated from HIV-1.
BACKGROUND: Development of systemic venous collaterals after Glenn or Fontan procedures can lead to systemic desaturation and reduction in ventricular function, resulting in impaired everyday performance in patients with univentricular heart disease. METHODS: We analyzed 79 patients who had undergone a Glenn or Fontan procedure between 1995 and 1999 for the incidence and predilection sites of systemic venous collaterals as well as the therapeutic options. RESULTS: In 16/79 (= 20.2%) patients, 19 veno-venous connections were detected 310 days (1-966 days) postoperatively. Locations were: brachiocephalic angles/pericardial veins (7), azygos/hemiazygos system (5), Thebesian veins (2), epidiaphragmatic veins (5). Drainage was to the pulmonary veins in 5, to the "left" atrium in 9, and to the IVC system in 5 patients. An isolated intervention became necessary because of low saturations in 5/16 pts, with improvement in all of them (catheter embolization 4, surgical closure 1). CONCLUSIONS: After Glenn or Fontan operations, the increased central venous pressure may induce recanalization of embryologically preformed and obliterated vessels. Their predilection sites must be carefully evaluated pre- and postoperatively. During surgical procedures, potential venous channels should be ligated. Interventional or surgical closure of collaterals may become necessary.