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BACKGROUND AND PURPOSE: Measurement of QT intervals during atrial flutter (AFL) is relevant to monitor the safety of drug delivery. Our aim is to compare QT and QTc intervals in AFL patients before and after catheter ablation in order to validate QT measurement during AFL. METHODS: 25 patients suffering from AFL underwent catheter ablation; 9 were in sinus rhythm and 16 were in AFL at the time of the procedure. Holter ECGs were continuously recorded before, during and after the procedure. In AFL signals, flutter waves were subtracted using a previously-validated deconvolution-based method. Fridericia's QTc was computed before and after ablation after hysteresis reduction. RESULTS: Comparing QTc values obtained before and after ablation showed that (1) the intervention did not significantly affect QTc, and (2) the QTc during AFL was concordant with the QTc value in sinus rhythm. CONCLUSION: QTc can be reliably measured in patients with AFL using flutter wave subtraction and hysteresis reduction.
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Aleteo Atrial/fisiopatología , Aleteo Atrial/cirugía , Ablación por Catéter/métodos , Sistema de Conducción Cardíaco/fisiopatología , Anciano , Electrocardiografía , Electrocardiografía Ambulatoria , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Técnica de SustracciónRESUMEN
AIMS: This study assessed whether (i) adolescents treated in hospital for acute alcohol intoxication show different habitual drinking patterns from adolescents of the general population and whether (ii) predictors for repeated treatment can be identified. METHODS: A sample of adolescents who had undergone inpatient treatment for intoxication (clinical sample) comprised n=482 under 18-year-old subjects, who had additionally been surveyed within the context of the project "Hart am Limit" (HaLT) between 2008 and 2010 (mean age: 15.1 years, 44.4% girls). The population sample consisted of n=1 994 Bavarian students who had taken part in the European School Survey Project on Alcohol and other Drugs (ESPAD) in 2007 (mean age: 15.7 years; 54.4% girls). RESULTS: Within the clinical sample, gender differences in age, level of education and motivation to get drunk were found. Adolescents of the clinical sample were on average younger and had a higher level of education than adolescents in the general population sample. Although students in the clinical sample drank alcohol less often (2.8 vs. 5.0 times within the past 30 days), they drank more alcohol per occasion (36.4 g vs. 22.3 g pure alcohol per drinking day). Assessments by a third-party show that the risk of repeated inpatient treatment due to alcohol intoxication is positively associated with perceived psychosocial stress and negatively associated with perceived family support. CONCLUSIONS: A hospitalisation due to alcohol intoxication does not sufficiently indicate alarming habitual drinking behaviour. The risk of hospitalisation seems to depend on the drinking context and other factors of the drinking situation. Nevertheless, a sub-group of adolescents, who seem to display an elevated risk for intoxications, could be identified. It is for this sub-group, that supportive measures must be made available.
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Consumo de Bebidas Alcohólicas/epidemiología , Consumo de Bebidas Alcohólicas/terapia , Intoxicación Alcohólica/epidemiología , Intoxicación Alcohólica/terapia , Hospitalización/estadística & datos numéricos , Pacientes Internos/estadística & datos numéricos , Estrés Psicológico/epidemiología , Adolescente , Distribución por Edad , Consumo de Bebidas Alcohólicas/psicología , Intoxicación Alcohólica/psicología , Comorbilidad , Escolaridad , Femenino , Alemania/epidemiología , Humanos , Incidencia , Pacientes Internos/psicología , Masculino , Factores de Riesgo , Distribución por Sexo , Estrés Psicológico/diagnóstico , Estrés Psicológico/psicologíaRESUMEN
Infections caused by blood-borne viruses such as hepatitis B and C and the human immunodeficiency virus (HIV) are associated commonly with needlestick injuries, especially in a hospital setting. A prospective investigation was conducted on a medical doctor who suffered an accidental needlestick injury during blood collection from a patient with AIDS. The patient's blood contained 195,000 copies of HIV RNA, 1 × 10(6) IU hepatitis C virus (HCV) RNA, and >10(7) copies of parvovirus B19 DNA per 1 ml plasma. It was positive for cytomegalovirus virus and evidence of a resolved hepatitis B virus (HBV) infection was found. HCV viremia was detected in the physician 15 days later and was not resolved by seroconversion after 57 days. HIV infection was not transmitted, possibly because of the immediate use of anti-HIV prophylactic drugs after exposure. Parvovirus B19 infection was presumably prevented by pre-existing specific antibodies in the patient. Considering that many HIV carriers are coinfected with hepatitis B and C viruses, this case report support the knowledge that the risk of HCV transmission from a patient with AIDS is greater than that of HIV.
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Patógenos Transmitidos por la Sangre/aislamiento & purificación , Sangre/virología , Hepatitis C/transmisión , Transmisión de Enfermedad Infecciosa de Paciente a Profesional , Lesiones por Pinchazo de Aguja/complicaciones , Adulto , VIH/aislamiento & purificación , Hepacivirus/aislamiento & purificación , Humanos , Parvovirus B19 Humano/aislamiento & purificación , Médicos , Carga ViralRESUMEN
When the second wave of pandemic influenza A H1N1v 2009 (H1N1v) emerged in the winter of 2010/2011, public health authorities were afraid of dangerous implications and severe clinical courses again. As further H1N1v waves might appear, achievement of sufficient herd immunity is a matter of urgency. The objective of this study was to determine the seroprevalence of antibodies against H1N1v by hemagglutination-inhibition test (HI) after the second wave. We compared our recent findings with our data obtained after the first pandemic in 2009/2010. Between March and May 2011 we collected serum samples from 600 persons aged 1 to 84 years admitted to University Hospital Frankfurt/Main and analysed the titres of anti-H1N1v by HI. The overall seroprevalence of anti-H1N1v has risen from 36.9% (95% confidence interval (95%CI), 33-41) in unvaccinated persons after the first wave to 57.3% (95%CI, 53.1-61.2) in vaccinated and unvaccinated. The highest rate of seropositivity was detected in the age group of 10-19 years (66%; 95%CI, 55.8-75.2), whereas the lowest was found in the age group 40-59 years (51%; 95%CI, 40.8-61.1). Although seroprevalence has significantly increased, sufficient herd immunity is still not achieved. Therefore, general vaccination programs have to be propagated continuously by public health authorities.
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Anticuerpos Antivirales/sangre , Subtipo H1N1 del Virus de la Influenza A/clasificación , Subtipo H1N1 del Virus de la Influenza A/aislamiento & purificación , Gripe Humana/epidemiología , Gripe Humana/virología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Femenino , Alemania/epidemiología , Pruebas de Inhibición de Hemaglutinación , Humanos , Inmunidad Colectiva , Lactante , Subtipo H1N1 del Virus de la Influenza A/inmunología , Gripe Humana/inmunología , Masculino , Persona de Mediana Edad , Estudios Seroepidemiológicos , Adulto JovenRESUMEN
The evolution of intra-host human immunodeficiency virus type 1 (HIV-1) quasispecies prior and after treating active tuberculosis (TB) with chemotherapy in HIV-1/TB patients was assessed. Two time points HIV-1 quasispecies were evaluated by comparing HIV-1-infected patients with active tuberculosis (HIV-1/TB) and HIV-1-infected patients without tuberculosis (HIV-1/non-TB). Plasma samples were obtained from the Frankfurt HIV cohort, and HIV-1 RNA was isolated. C2V5 env was amplified by PCR and molecular cloning was performed. Eight to twenty-five clones were sequenced from each patient. Various phylogenetic analyses were performed. We found a significant increase in diversity and divergence in HIV-1/TB compared to the HIV-1/non-TB. For HIV-1/TB, the average rate of evolution of C2V5 env was higher than previous reports (2.4 × 10(-4) substitution/site/day). Two groups of HIV-1/TB were observed based on the rate of HIV-1 evolution and coreceptor usage: A fast evolving R5-tropic dominating group and a relatively slowly evolving X4 group. The results demonstrated that active TB has an impact on HIV-1 viral diversity and divergence over time. The influence of active TB on longitudinal evolution of HIV-1 may be predominant for R5 viruses.
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Evolución Molecular , Infecciones por VIH/complicaciones , Infecciones por VIH/virología , VIH-1/clasificación , VIH-1/genética , Tuberculosis/complicaciones , Adulto , Antituberculosos/uso terapéutico , Clonación Molecular , Femenino , Genotipo , VIH-1/aislamiento & purificación , Humanos , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , Plasma/virología , Reacción en Cadena de la Polimerasa , Polimorfismo Genético , ARN Viral/genética , ARN Viral/aislamiento & purificación , Receptores del VIH , Análisis de Secuencia de ADN , Tuberculosis/tratamiento farmacológico , Acoplamiento Viral , Productos del Gen env del Virus de la Inmunodeficiencia Humana/genéticaRESUMEN
HIV-1 diversity poses major challenges to viral load assays because genetic polymorphisms can impede nucleic acid detection. In addition to the on-going viral diversification within the HIV-1 group M pandemic, HIV-1 genetic diversity is further increased by non-group M infections, such as HIV-1 groups O (HIV-1-O), N and P. We here conducted a systematic evaluation of commercially available PCR assays to detect HIV-1-O isolates. We collected 25 primary HIV-1-O isolates covering all genetic clusters within HIV-1-O. Subsequently, this panel of isolates was tested on eight commercially available quantitative and five qualitative HIV-1 PCR-based assays in serial dilutions. Sequence analyses were performed for severe cases of underquantification or lack of detection. We observed differences between the assays in quantification that depended on the HIV-1-O isolate's subgroup. All three tested HIV-1-O subgroup IV isolates were underquantified by the Roche CAP/CTM >800-fold compared to the Abbott RealTime assay. In contrast, the latter assay underquantified several subgroup I isolates >200-fold. Notably, the Xpert HIV-1 Viral Load test from Cepheid failed to detect two of the HIV-1-O isolates, whereas the Roche Cobas 8800 assay readily detected all isolates. Comparative sequence analyses identified polymorphisms in the HIV-1-O long-terminal repeat and integrase genes that likely underlie inadequate nucleic acid amplification. Potential viral load underquantification should be considered in therapeutic monitoring of HIV-1-O-infected patients. Pre-clinical assessments of HIV-1 diagnostic assays could be harmonized by establishing improved and internationally standardized panels of HIV-1 isolates that cover the dynamic diversity of circulating HIV-1 strains.
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Infecciones por VIH , VIH-1 , Técnicas de Amplificación de Ácido Nucleico , Carga Viral , Infecciones por VIH/diagnóstico , Infecciones por VIH/virología , VIH-1/clasificación , VIH-1/genética , Humanos , Técnicas de Amplificación de Ácido Nucleico/métodos , Técnicas de Amplificación de Ácido Nucleico/normas , ARN Viral/análisis , ARN Viral/genética , Reproducibilidad de los Resultados , Carga Viral/métodos , Carga Viral/normasRESUMEN
BACKGROUND: The EU approval of enfuvirtide (Fuzeon) was granted in May 2003 on the basis of the 48-week data from the TORO 1 and TORO 2 studies. Enfuvirtide is licensed for use in pretreated HIV patients experienced with three classes of drugs who exhibited treatment failure or who have shown intolerance to previous antiretroviral treatment regimens. Recent studies with the new protease inhibitors tipranavir and darunavir (RESIST and POWER studies) showed that a high proportion of heavily pretreated HIV patients achieve a viral load reduction to below the limit of detection when treated with enfuvirtide plus one of these new ritonavir-boosted protease inhibitors and an optimised background treatment regimen. The International AIDS Society (IAS-USA Panel) has recently updated its treatment guidelines in view of these new data and recommends the use of an antiretroviral treatment regimen containing at least two active drugs, one of which that has a new mechanism of action, for HIV patients who have been heavily pretreated. A new treatment goal has also emerged for heavily pretreated patients with advanced HIV disease: reduction of the viral load to below the detection limit of 50 copies/ml. The IAS concluded that the likelihood of achieving this treatment goal is higher when enfuvirtide is selected as one of the two active drugs. OBJECTIVE: A panel of German experts convened to discuss the currently available data and to incorporate them into the updated German consensus recommendations for the use of enfuvirtide when switching treatment in heavily pretreated HIV patients. METHODS: The consensus recommendations are based on published data from controlled, randomised clinical studies and on the expert opinions of the discussants. RESULTS AND CONCLUSIONS: The consensus recommendations were developed to provide practice-relevant standardised recommendations for selecting suitable candidates for enfuvirtide therapy and for their management. Aspects including predictive prognostic factors, disease stage, selection of the optimised background regimen, early indicators of a response to enfuvirtide, as well as accompanying educational measures treatment were considered. New protease inhibitors or other remaining active drugs should be used together with enfuvirtide in heavily pretreated patients in order to enable at least two active drugs to be included in such a salvage regimen.
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Proteína gp41 de Envoltorio del VIH/uso terapéutico , Inhibidores de Fusión de VIH/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Fragmentos de Péptidos/uso terapéutico , Algoritmos , Ensayos Clínicos Fase III como Asunto , Farmacorresistencia Viral , Enfuvirtida , Alemania , Proteína gp41 de Envoltorio del VIH/administración & dosificación , Proteína gp41 de Envoltorio del VIH/efectos adversos , Inhibidores de Fusión de VIH/administración & dosificación , Inhibidores de Fusión de VIH/efectos adversos , Infecciones por VIH/virología , Inhibidores de la Proteasa del VIH/efectos adversos , Inhibidores de la Proteasa del VIH/uso terapéutico , Humanos , Educación del Paciente como Asunto , Fragmentos de Péptidos/administración & dosificación , Fragmentos de Péptidos/efectos adversos , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del Tratamiento , Carga ViralRESUMEN
BACKGROUND: Maternal CD4+ cell microchimerism may be greater after caesarean section compared to spontaneous vaginal delivery and could cause mother-to-child transmission (MTCT) in HIV-exposed newborns. AIMS: To evaluate maternal CD4+ cell microchimerism in HIV-exposed newborns after spontaneous vaginal delivery or caesarean section. STUDY DESIGN AND SUBJECTS: In this prospective single-centre study, neonates whose mothers were infected with HIV and had normal MTCT risk according to the German Austrian Guidelines were considered for study enrolment. Maternal CD4+ cell microchimerism in the newborns' umbilical cord blood was measured and compared by mode of delivery. RESULTS: Thirty-seven HIV-infected mothers and their 39 newborns were included in the study. None of the 17 (0.0%) newborns delivered vaginally had quantifiable maternal CD4+ cells (95% confidence interval (CI): 0.00-0.00) in their circulation at birth compared with four of 16 (25.0%) newborns delivered via planned caesarean section, who showed 0.01-0.66% maternal cells (95% CI: -0.06-0.16; P=0.02) in their circulation. The intention to treat analysis, which included six additional newborns delivered by unplanned caesarean section, showed quantifiable maternal CD4+ cells in one (0.05%; 95% CI: -0.02-0.04) of 23 (4.3%) newborn at birth compared to four of 16 (25.0%) born via planned caesarean section (95% CI: -0.06-0.16; P=0.04). There was no MTCT in any of the newborns. CONCLUSION: In this small cohort, spontaneous vaginal delivery in HIV-infected women with normal MTCT risk was associated with lower maternal CD4+ cell transfer to newborns compared to planned caesarean section.
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Linfocitos T CD4-Positivos/virología , Cesárea/efectos adversos , Infecciones por VIH/sangre , Transmisión Vertical de Enfermedad Infecciosa , Complicaciones Infecciosas del Embarazo/sangre , Adulto , ADN Viral/genética , Femenino , Infecciones por VIH/transmisión , Humanos , Recién Nacido , Masculino , EmbarazoRESUMEN
OBJECTIVE: In an intent-to-treat study, reduction of viral load, increase in CD4 cell count, clinical benefit and adverse reactions were examined in HIV-infected children receiving first line therapy including efavirenz. METHODS: The data of 10 perinatally infected children (median age: 5.8 years) were evaluated during a treatment period of 24 months. Viral load and CD4 cell count were measured every 4 - 8 weeks. Pharmacokinetic evaluations of efavirenz were performed in all patients at study onset. Adverse reactions were reported after obtaining interval history and examination. RESULTS: At base line, median CD4 cell count was 378 cells/microl (21%) and median viral load was 350,000 copies/ml (5.5 log10 copies/ml). After 24 months of treatment, the median viral load reduction was > 3.5 log10 copies/ ml and HIV-1 RNA < 50 copies/ml was found in 8/10 children (80%). Median CD4 cell count increased to 721 cells/microl (24%) after 3 months and was maintained at a level of >1000 cells/microl (> 25%) after 24 months of treatment. Regarding efavirenz levels, C min. values ranged from 845 to 3550 ng/ml (median: 1845 ng/ml) and C max. values from 2380 to 24 200 ng/ ml (median: 3670 ng/ml). The most common adverse effect was a mild skin rash (4/10 children). CNS symptoms were recorded in one patient and no hyperlipidaemia was seen. CONCLUSION: First line therapy with efavirenz and two NRTIs was well tolerated by HIV-1 infected children and the reduction of viral load seems to be similar to single protease inhibitor-containing regimens.
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Fármacos Anti-VIH/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Oxazinas/uso terapéutico , Inhibidores de la Transcriptasa Inversa/uso terapéutico , Administración Oral , Alquinos , Fármacos Anti-VIH/efectos adversos , Fármacos Anti-VIH/farmacocinética , Benzoxazinas , Recuento de Linfocito CD4 , Niño , Preescolar , Ciclopropanos , Farmacorresistencia Viral , Quimioterapia Combinada , Exantema/inducido químicamente , Femenino , Genotipo , Infecciones por VIH/virología , VIH-1/efectos de los fármacos , VIH-1/genética , VIH-1/crecimiento & desarrollo , Humanos , Masculino , Oxazinas/efectos adversos , Oxazinas/farmacocinética , Estudios Prospectivos , ARN Viral/análisis , Inhibidores de la Transcriptasa Inversa/efectos adversos , Inhibidores de la Transcriptasa Inversa/farmacocinética , Carga ViralRESUMEN
OBJECTIVES: In diabetes accumulated advanced glycation end products (AGEs) are involved in the striking cardiovascular morbidity/mortality. We asked whether a hypovitaminosis D associates with an increased formation and toxicity of AGEs in diabetes. METHODS: In 276 diabetics (160 M/116 F, age: 65.0 ± 13.4; 43 type 1,T1DM, and 233 type 2 patients, T2DM) and 121 nondiabetic controls (60 M/61 F; age: 58.6 ± 15.5 years) routine biochemistry, levels of 25-hydroxyvitamin D3 (25-(OH)D), skin autofluorescence (SAF), plasma AGE-associated fluorescence (AGE-FL), N (ε) -(carboxymethyl)lysine (CML), soluble receptor for AGEs (sRAGE), soluble vascular adhesion protein-1 (sVAP-1), high sensitive C-reactive protein (hs-CRP), and renal function (eGFR) were determined. RESULTS: In the diabetics SAF and AGE-Fl were higher than those of the controls and correlated with age, duration of diabetes, and degree of renal impairment. In T2DM patients but not in T1DM the age-dependent rise of SAF directly correlated with hs-CRP and sVAP-1. 25-(OH)D levels in diabetics and nondiabetics were lowered to a similar degree averaging 22.5 ng/mL. No relationship between 25-(OH)D and studied markers except for sVAP-1 was observed in the diabetics. CONCLUSION: In diabetics hypovitaminosis D does not augment accumulation of AGEs and studied markers of microinflammation and oxidative stress except for sVAP-1.
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Diabetes Mellitus/sangre , Productos Finales de Glicación Avanzada/sangre , Inflamación/sangre , Deficiencia de Vitamina D/sangre , Vitamina D/sangre , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Proteína C-Reactiva/metabolismo , Estudios de Casos y Controles , Diabetes Mellitus/patología , Femenino , Humanos , Inflamación/complicaciones , Inflamación/patología , Masculino , Persona de Mediana Edad , Estrés Oxidativo , Deficiencia de Vitamina D/complicaciones , Deficiencia de Vitamina D/patologíaRESUMEN
OBJECTIVE: To investigate the prevalence and magnitude of M184V-mediated changes in susceptibility to zalcitabine, didanosine, stavudine and abacavir (1592U89 succinate) in a cohort of lamivudine-treated patients. DESIGN AND METHODS: A total of 255 samples from patients treated with lamivudine and zidovudine with or without other nucleoside reverse transcriptase inhibitors (NRTI) were analysed for susceptibility to zidovudine, lamivudine, zalcitabine, didanosine and stavudine using a recombinant virus assay. Seventy-three samples originated from patients exposed to zidovudine and lamivudine only. A subset of 27 samples was investigated for cross-resistance to abacavir. Resistance was defined as a change in median inhibitory concentration more than fivefold compared with wild-type (high-level resistance, > 10-fold). A genotypic analysis of plasma-derived reverse transcriptase coding regions was carried out in samples with cross-resistance. RESULTS: The majority of samples displayed wild-type or greater than wild-type sensitivity to zalcitabine, didanosine and stavudine: resistance was seen in 17.2, 9 and 6.3% of the total sample population, respectively. Of these, 1.2, 2.7 and 2.4%, respectively, showed high-level resistance. The prevalence of resistance to a particular NRTI was lower in samples from patients not pretreated with that NRTI and in samples from patients exposed to zidovudine-lamivudine only. Cross-resistance was more prevalent in samples with high ZDV resistance. There was no obvious correlation between cross-resistance and genotype; all but two samples were mutant at codon 184. There were no consistent changes at positions associated with zidovudine resistance. The majority of samples from a subset (n=27) were four- to eightfold less sensitive to abacavir. There were no other genotypic changes in addition to M184V known to be associated with abacavir resistance. CONCLUSIONS: Cross-resistance was not commonly observed in this lamivudine-treated cohort. M184V per se is not expected to compromise subsequent treatment with NRTI such as didanosine-stavudine or combinations containing abacavir.
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Fármacos Anti-VIH/farmacología , Didesoxinucleósidos/farmacología , Resistencia a Múltiples Medicamentos/genética , Infecciones por VIH/tratamiento farmacológico , Transcriptasa Inversa del VIH/genética , VIH-1/efectos de los fármacos , Lamivudine/farmacología , Mutación Puntual , Inhibidores de la Transcriptasa Inversa/farmacología , Estudios de Cohortes , Didanosina/farmacología , Farmacorresistencia Microbiana , Quimioterapia Combinada , Infecciones por VIH/virología , VIH-1/enzimología , VIH-1/genética , Humanos , Metionina/genética , Estavudina/farmacología , Valina/genética , Zalcitabina/farmacología , Zidovudina/farmacologíaRESUMEN
The emergence of drug resistance remains a major problem during antiretroviral treatment of patients infected with human immunodeficiency virus type 1 (HIV-1). As phenotypic drug resistance is laborious and expensive to determine, and because numerous specific mutations are known to be correlated with different resistance patterns, genotyping of the reverse transcriptase and protease genes of HIV is fast becoming an integral part of HIV management in industrialized countries. A number of software-based interpretation systems have been developed for the interpretation of the resulting complex nucleotide sequences. These programs either employ rule-based algorithms or are based on a genotype-phenotype database. This paper reviews recent publications that compare different such systems, trying to identify the degree of discordance between different systems and the reasons underlying such discrepant interpretations. The highest discordance rate was observed for nucleoside reverse transcriptase inhibitors (NRTIs) followed by protease inhibitors (PIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs). For the NRTIs, it is the role of nucleoside analogue associated mutations, for the PIs and for the NNRTIs, that of secondary mutations that causes most discrepancies. As the complexity of the mutation pattern is likely to increase further with new drugs becoming available, rule-based genotype interpretation algorithms need to be updated frequently. Whilst not recommending one particular system, the authors believe that the correlation of genotypic with clinical data is probably the best way to develop an optimal algorithm.
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Interpretación Estadística de Datos , Farmacorresistencia Viral Múltiple/genética , Inhibidores de la Proteasa del VIH/farmacología , VIH-1/genética , Inhibidores de la Transcriptasa Inversa/farmacología , Algoritmos , Variación Genética , VIH-1/clasificación , Humanos , Mutación Puntual , Programas InformáticosRESUMEN
In a retrospective study of 28 women and eight men with squamous cell metaplasia in different parts of the bladder, including the trigone, no histopathological differences were observed among the regions. All the five (female) patients with parakeratosis had a concomitant invasive bladder tumour. Thirty-eight% of all the patients had a simultaneous neoplastic tumour. The metaplastic lesions were investigated for keratin in 13 patients, and all were positive. In seven out of eight patients, the urothelium adjacent to the squamous cell metaplasia was also positive for keratin, indicating a direct transformation of the urothelium to squamous cell epithelium. The metaplastic cells were investigated for oestrogen receptors in five men and five women, and all were negative, suggesting no relationship between estrogens and squamous cell metaplasia of the bladder. Squamous cell metaplasia in the bladder is not considered a premalignant condition. However, metaplasia and neoplastic tumours are often associated with chronic tissue damage, and the presence of metaplasia may give a warning of conditions that can also cause cancer.
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Vejiga Urinaria/patología , Adulto , Anciano , Epitelio/química , Epitelio/patología , Femenino , Humanos , Queratinas/análisis , Masculino , Metaplasia/patología , Persona de Mediana Edad , Receptores de Estrógenos/análisis , Estudios Retrospectivos , Vejiga Urinaria/químicaRESUMEN
An acute and often severe respiratory illness emerged in southern China in late 2002 and rapidly spread to different areas of the Far East as well as several countries around the globe. When the outbreak of this apparently novel infectious disease termed severe acute respiratory syndrome (SARS) came to an end in July 2003, it had caused over 8000 probable cases worldwide and more than 700 deaths. Starting in March 2003, the World Health Organization (WHO) organised an unprecedented international effort by leading laboratories working together to find the causative agent. Little more than one week later, three research groups from this WHO-coordinated network simultaneously found evidence of a hitherto unknown coronavirus in SARS patients, using different approaches. After Koch's postulates had been fulfilled, WHO officially declared on 16 April 2003 that this virus never before seen in humans is the cause of SARS. Ever since, progress around SARS-associated coronavirus (SARS-CoV) has been swift. Within weeks of the first isolate being obtained, its complete genome was sequenced. Diagnostic tests based on the detection of SARS-CoV RNA were developed and made available freely and widely; nevertheless the SARS case definition still remains based on clinical and epidemiological criteria. The agent's environmental stability, methods suitable for inactivation and disinfection, and potential antiviral compounds have been studied, and development of vaccines and immunotherapeutics is ongoing. Despite its grave consequences in humanitarian, political and economic terms, SARS may serve as an example of how much can be achieved through a well-coordinated international approach, combining the latest technological advances of molecular virology with more "traditional" techniques carried out to an excellent standard.
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Control de Enfermedades Transmisibles , Enfermedades Transmisibles Emergentes/epidemiología , Síndrome Respiratorio Agudo Grave/epidemiología , Coronavirus Relacionado al Síndrome Respiratorio Agudo Severo/aislamiento & purificación , Antivirales/uso terapéutico , China/epidemiología , Enfermedades Transmisibles Emergentes/diagnóstico , Enfermedades Transmisibles Emergentes/tratamiento farmacológico , Enfermedades Transmisibles Emergentes/transmisión , Humanos , Coronavirus Relacionado al Síndrome Respiratorio Agudo Severo/clasificación , Síndrome Respiratorio Agudo Grave/diagnóstico , Síndrome Respiratorio Agudo Grave/tratamiento farmacológico , Síndrome Respiratorio Agudo Grave/transmisión , Organización Mundial de la SaludRESUMEN
OBJECTIVES: The reverse transcriptase (RT)-mutation K65R limits further therapeutic options and has been selected by unfavorable RT-combinations, e.g. tenofovir in combination with abacavir and/or didanosine. METHODS: We identified HIV-1 infected patients from a large treatment cohort who experienced virological failure (HIV-1 RNA >1000 copies/mL) with evidence of resistance mutations including the K65R, but without thymidine analogue mutations (TAMs) in genotypic resistance assay. Phenotype was performed from previously collected frozen plasma. The patients were followed for clinical and resistance outcome after treatment intensification with only zidovudine. RESULTS: Five patients had experienced antiretroviral treatment failure on various nucleoside analogue combinations, containing abacavir, didanosine, lamivudine, nevirapine, reverset and/or tenofovir. RT-sequence revealed mutations at position K65R in combination with other non-TAMs. The patients' median viral load prior to zidovudine intensification was 3.551 Log10 (range 3.053-4.681) and despite evidence for resistance to the failing drug regimen, all responded within 4 weeks to undetectable levels (<1.699 Log10 or <50 copies/mL) and remained virologically suppressed during follow-up (20 months through 6.5 years). CONCLUSIONS: In virologically failing patients due to K65R- and other non-thymidine-mutations, simple regimen intensification with zidovudine resulted in sustained HIV-1 suppression. The finding of re-sensitized HIV-1 in patients may be clinically relevant.
Asunto(s)
Fármacos Anti-VIH/administración & dosificación , Terapia Antirretroviral Altamente Activa/métodos , Farmacorresistencia Viral , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/virología , VIH-1/efectos de los fármacos , Zidovudina/administración & dosificación , Adulto , Sustitución de Aminoácidos , Femenino , Transcriptasa Inversa del VIH/genética , Humanos , Masculino , Pruebas de Sensibilidad Microbiana/métodos , Persona de Mediana Edad , Mutación Missense , Terapia Recuperativa/métodos , Insuficiencia del Tratamiento , Resultado del Tratamiento , Carga ViralRESUMEN
Although classical influenza is a clinically typical illness ("unchanging disease due to a changing agent"), laboratory investigations are essential at the beginning of each influenza epidemic. They should confirm suspected influenza cases and exclude "flu-like illnesses" which may be caused by numerous other viral and bacterial agents. Different virological as well as serological methods are available. For early diagnosis of acute influenza virus infections, virus detection using rapid procedures for virus isolation or antigen staining and molecular biological techniques have been developed. The determination of specific antibodies (IgG, IgM) has traditionally been widely used diagnostically. Conventional serological diagnosis is possible by means of the complement fixation and hemagglutination inhibition tests and allows the detection of type- and subtype-specific antibodies, respectively. As part of an automated serology, immunofluorescence test and enzyme-linked immunosorbent assay are the mostly widely available methods. In comparison, virus detection is clearly superior to antibody determination for diagnosis of influenza virus infections. However, antibody testing may be useful as a complementary tool to confirm the diagnosis retrospectively.
Asunto(s)
Gripe Humana/diagnóstico , Orthomyxoviridae/aislamiento & purificación , Pruebas Serológicas , Anticuerpos Antivirales/sangre , Técnica del Anticuerpo Fluorescente , Humanos , Virus de la Influenza A/clasificación , Virus de la Influenza A/patogenicidad , Virus de la Influenza B/clasificación , Virus de la Influenza B/patogenicidad , Gripe Humana/clasificación , Gripe Humana/epidemiología , Técnicas de Diagnóstico Molecular , Orthomyxoviridae/genética , Orthomyxoviridae/inmunología , Manejo de Especímenes/normasRESUMEN
Prions are a novel class of infectious agents that cause subacute encephalopathy in man and animals as human Creutzfeldt-Jakob disease (CJD), sheep scrapie and bovine spongiform encephalopathy (BSE). Previously, prions were shown to be transmitted by neuro- and ophthalmosurgical measures and by application of brain-derived therapeutic hormones. Recently, prions have been detected in blood specimens of experimentally infected monkeys indicating a principal threat to transfusion medicine, furthermore in human or bovine materials used in reconstructive surgery. In this article the risk of prion transmission from the surgeon to the patient or vice versa during (orthopedic) surgery is reevaluated including the issues of blood transfusion. This is accomplished based on recent epidemiologic findings and biometric calculations on the spread of prions in animals and humans as well as in terms of experimental data on artificially contaminated medical materials and devices. The overall risk of prion transmission in orthopedic surgery is considered very low if adequately prepared and sterilized materials and devices are used.
Asunto(s)
Transmisión de Enfermedad Infecciosa , Procedimientos Ortopédicos , Enfermedades por Prión/epidemiología , Enfermedades por Prión/transmisión , Priones/aislamiento & purificación , Animales , Bovinos , Control de Enfermedades Transmisibles , Síndrome de Creutzfeldt-Jakob/epidemiología , Síndrome de Creutzfeldt-Jakob/cirugía , Síndrome de Creutzfeldt-Jakob/transmisión , Encefalopatía Espongiforme Bovina/epidemiología , Encefalopatía Espongiforme Bovina/cirugía , Encefalopatía Espongiforme Bovina/transmisión , Humanos , Incidencia , Prevención Primaria , Enfermedades por Prión/cirugía , Pronóstico , Medición de Riesgo , Factores de Riesgo , Ovinos , Tasa de SupervivenciaRESUMEN
Noroviruses (NV) are transmitted by fecally contaminated food, vomit, and person-to-person contact. They are one of the main causes of non-bacterial acute gastroenteritis in nursing, old people and children's homes. NV outbreaks are characterized by a short incubation period (12-48 h), nausea, vomiting and diarrhea, and high secondary attack rates. The illness is generally mild and self-limiting. The aim of diagnostic procedures in viral gastroenteritis is to avoid nosocomial infections on the one hand and unnecessary antibiotic treatment on the other. Diagnostic procedures for NV are based on the detection of virus in stool samples by (immune) transmission electron microscopy (TEM), antigen ELISA, or polymerase chain reaction (PCR). In our study, a total of 244 stool samples obtained from 227 patients between March and May 2002 were tested by TEM, antigen ELISA and in-house PCR. Our data showed that PCR has the highest sensitivity (94.1%), followed by TEM (58.3%), and ELISA (31.3%), while specificity was highest for TEM (98.0%), followed by ELISA (94.9%), and PCR (92.4%). All three methods tested (TEM, ELISA and PCR) are useful for epidemiological investigations in gastroenteritis outbreaks; however, to maximize diagnostic validity for individual cases, at least two of the methods should be combined.
Asunto(s)
Infecciones por Caliciviridae/diagnóstico , Adulto , Anciano , Antígenos Virales/análisis , Secuencia de Bases , Caliciviridae/genética , Caliciviridae/inmunología , Caliciviridae/aislamiento & purificación , Caliciviridae/ultraestructura , Infecciones por Caliciviridae/transmisión , Infecciones por Caliciviridae/virología , ADN Viral/genética , Ensayo de Inmunoadsorción Enzimática/estadística & datos numéricos , Heces/virología , Femenino , Humanos , Masculino , Microscopía Inmunoelectrónica , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/estadística & datos numéricos , Sensibilidad y EspecificidadRESUMEN
Human immunodeficiency virus type 1 (HIV-1) strains resistant to nonnucleoside reverse transcriptase inhibitors (NNRTIs) may easily be selected for in vitro and in vivo under a suboptimal therapy regimen. Although cross-resistance is extensive within this class of compounds, newer NNRTIs were reported to retain activity against laboratory strains containing defined resistance-associated mutations. We have characterized HIV-1 resistance to loviride and the extent of cross-resistance to nevirapine, delavirdine, efavirenz, HBY-097, and tivirapine in a set of 24 clinical samples from patients treated with long-term loviride monotherapy by using a recombinant virus assay. Genotypic changes associated with resistance were analyzed by population sequencing. Overall, phenotypic resistance to loviride ranged from 0.04 to 3.47 log10-fold. Resistance was observed in samples from patients who had discontinued loviride for up to 27 months. Cross-resistance to the other compounds was extensive; however, fold resistance to efavirenz was significantly lower than fold resistance to nevirapine. No genotypic changes were detected in three samples; these were sensitive to all of the NNRTIs tested. The most common genotypic change was the K103N substitution. The range of phenotypic resistance in samples containing the K103N substitution could not be predicted from a genotypic analysis of known NNRTI resistance-associated mutations. The Y181C substitution was detected in one isolate which was resistant to loviride and delavirdine but sensitive to efavirenz, HBY-097, and tivirapine. Our data indicate that the available newer NNRTIs which retain activity against some HIV-1 strains selected by other compounds of this class in vitro may have compromised clinical efficacy in some patients pretreated with NNRTI.
Asunto(s)
Acetamidas/farmacología , Acetofenonas/farmacología , Fármacos Anti-VIH/farmacología , Transcriptasa Inversa del VIH/antagonistas & inhibidores , VIH-1/efectos de los fármacos , Inhibidores de la Transcriptasa Inversa/farmacología , Acetamidas/uso terapéutico , Acetofenonas/uso terapéutico , Fármacos Anti-VIH/uso terapéutico , Farmacorresistencia Microbiana , Resistencia a Múltiples Medicamentos , Genotipo , Transcriptasa Inversa del VIH/genética , VIH-1/genética , Humanos , Pruebas de Sensibilidad Microbiana , Mutación , Fenotipo , Estudios RetrospectivosRESUMEN
To investigate the occurrence of multinucleoside analog resistance during therapy failure, we surveyed the drug susceptibilities and genotypes of nearly 900 human immunodeficiency virus type 1 (HIV-1) samples. For 302 of these, the 50% inhibitory concentrations of at least four of the approved nucleoside analogs had fourfold-or-greater increases. Genotypic analysis of the reverse transcriptase (RT)-coding regions from these samples revealed complex mutational patterns, including the previously recognized codon 151 multidrug resistance cluster. Surprisingly, high-level multinucleoside resistance was associated with a diverse family of amino acid insertions in addition to "conventional" point mutations. These insertions were found between RT codons 67 and 70 and were commonly 69Ser-(Ser-Ser) or 69Ser-(Ser-Gly). Treatment history information showed that a common factor for the development of these variants was AZT (3'-azido-3'-deoxythymidine, zidovudine) therapy in combination with 2',3'-dideoxyinosine or 2',3'-dideoxycytidine, although treatment patterns varied considerably. Site-directed mutagenesis studies confirmed that 69Ser-(Ser-Ser) in an AZT resistance mutational background conferred simultaneous resistance to multiple nucleoside analogs. The insertions are located in the "fingers" domain of RT. Modelling the 69Ser-(Ser-Ser) insertion into the RT structure demonstrated the profound direct effect that this change is likely to have in the nucleoside triphosphate binding site of the enzyme. Our data highlight the increasing problem of HIV-1 multidrug resistance and underline the importance of continued resistance surveillance with appropriate, sufficiently versatile genotyping technology and phenotypic drug susceptibility analysis.