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BACKGROUND: Hearing loss leads to increased irritability and disengagement in social activities and conversations, which may impact quality of life. Dental professionals are at risk of developing hearing loss through daily exposure to noise from a wide range of equipment that produces significantly high decibels and noise frequencies. AIMS: The aim of this systematic review was to investigate the risk of hearing loss in dental professionals, including dentists, dental specialists, dental hygienists and dental assistants. METHODS: This review was conducted following the Cochrane Handbook for Systematic Reviews. PubMed, Scopus, Embase, Cochrane, Science Direct, Google Scholar and ProQuest were searched up to March 2023. Seventeen of 416 studies met the inclusion criteria. Quality assessment was performed according to the Newcastle-Ottawa Scale for cohort and case-control studies, and a modified version of this tool for cross-sectional studies. RESULTS: The majority of included studies (82%) found a positive association with hearing loss for dentists and dental specialists, with years of clinical experience identified as a prominent risk factor. Dental hygienists and dental assistants were less commonly reported in the literature. Difference between the left and right ears was found in 71% of studies, with the left ear more affected in both dentists and dental assistants due to proximity to the noise-inducing equipment. CONCLUSIONS: Dental professionals are at risk of hearing loss in their workplace, especially linked to years of clinical experience, which highlights the need for prevention and appropriate ear-protective devices.
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BACKGROUND: Systemic juvenile idiopathic arthritis (sJIA) is a complex disease with an autoinflammatory component of unknown etiology related to the innate immune system. A major role in the pathogenesis has been ascribed to proinflammatory cytokines like interleukin-6 (IL-6), and effective drugs inhibiting their signaling are being developed. This study evaluates sJIA patients treated with the IL-6 inhibitor tocilizumab (TCZ) concerning clinical response rate, disease course and adverse effects in a real-life clinical setting. METHODS: In 2009 a clinical and research consortium was established, including an online registry for autoinflammatory diseases (AID) ( https://aid-register.de ). Data for this retrospective TCZ study were documented by 13 centers. RESULTS: From 7/2009 to 4/2014, 200 patients with sJIA were recorded in the AID-registry. Out of these, 46 (19 m, 27 f, age 1-18 years) received therapy with TCZ. Long term treatment (median 23 months) has been documented in 24/46 patients who were evaluated according to Wallace criteria (active disease 6/24, inactive disease 5/24, remission 13/24 cases). Under observation co-medication were used in 40/46 cases. Adverse events were reported in 11/46 patients. The clinical response rate (no clinical manifestation, no increased inflammation parameters) within the first 12 weeks of treatment was calculated to be 35%. CONCLUSION: Out of 200 sJIA children reported in the German AID-registry, 46 were treated with TCZ, showing a clinical response rate of 35% during the first 12 weeks, and inactive disease and/or remission under medication in 75% after one year. Adverse events were seen in 24% and severe adverse events in 4%. TRIAL REGISTRATION: The AID-Registry is funded by the BMBF (01GM08104, 01GM1112D, 01GM1512D).
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Anticuerpos Monoclonales Humanizados/uso terapéutico , Artritis Juvenil/tratamiento farmacológico , Interleucina-6/antagonistas & inhibidores , Adolescente , Anticuerpos Monoclonales Humanizados/efectos adversos , Niño , Preescolar , Femenino , Alemania , Humanos , Masculino , Sistema de Registros , Inducción de Remisión , Estudios Retrospectivos , Resultado del Tratamiento , Adulto JovenRESUMEN
OBJECTIVE: To evaluate the impact of rapidly identifying coagulase-negative staphylococci (CoNS) from positive blood cultures combined with an established antimicrobial stewardship (AS) programme at a tertiary cancer centre. METHODS: We compared cancer patients ≥18 years old who between 01/1/13 and 12/31/13 had one or more positive CoNS blood culture(s) identified by Staphylococcus QuickFISH® (a peptide nucleic acid fluorescence in situ hybridization assay) with cancer patients ≥18 years old who had CoNS identified by standard microbiological techniques between 01/01/11 and 12/31/11 (baseline). Positive blood culture results were reported to the clinician by microbiology staff; restricted antibiotics (e.g., vancomycin) required approval by the AS team. RESULTS: There were 196 baseline and 103 QuickFISH patients. Faster median time to organism identification (33 (IQR 27-46) versus 49 (IQR 39-63) hours, p < 0.001), more vancomycin avoidance (51/103 (50%) versus 60/196 (31%), p 0.002), shorter median antibiotic duration (1 (IQR 0-3) versus 2 (IQR 0-6) days, p 0.019), fewer central venous catheter (CVC) removals (14/78 (18%) versus 57/160 (36%), p 0.004), and reduced vancomycin level monitoring (16/52 (31%) versus 71/136 (52%), p 0.009) were observed in the QuickFISH group. QuickFISH implementation was predictive of a lower likelihood of antibiotic therapy prescription (OR 0.35, 95%CI 0.20-0.62, p < 0.001). Prior transplant (RR 1.47, 95%CI 1.13-1.92, p 0.004), neutropenia (RR 1.47, 95%CI 1.09-1.99, p 0.012), multiple positive blood cultures (RR 4.23, 95%CI 3.23-5.54, p < 0.001), and CVC (RR 1.60, 95%CI 1.02-2.53, p 0.043) were independent factors for antibiotic duration. CONCLUSIONS: QuickFISH implementation plus AS support leads to greater avoidance of vancomycin therapy and improved resource utilization in cancer patients with CoNS blood cultures.
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Programas de Optimización del Uso de los Antimicrobianos/estadística & datos numéricos , Hibridación Fluorescente in Situ/estadística & datos numéricos , Neoplasias/microbiología , Infecciones Estafilocócicas/sangre , Infecciones Estafilocócicas/diagnóstico , Staphylococcus/aislamiento & purificación , Vancomicina/efectos adversos , Adulto , Anciano , Anciano de 80 o más Años , Antibacterianos/uso terapéutico , Bacteriemia/diagnóstico , Bacteriemia/microbiología , Técnicas Bacteriológicas , Cultivo de Sangre , Técnicas de Laboratorio Clínico , Coagulasa/deficiencia , Femenino , Humanos , Hibridación Fluorescente in Situ/métodos , Masculino , Persona de Mediana Edad , Neoplasias/complicaciones , Infecciones Estafilocócicas/tratamiento farmacológico , Infecciones Estafilocócicas/microbiología , Staphylococcus/enzimología , Staphylococcus/genética , Vancomicina/uso terapéutico , Adulto JovenRESUMEN
Thalidomide, lenalidomide and bortezomib have increasingly been incorporated in first-line induction therapies for multiple myeloma. Concerns regarding the impact of these agents, especially lenalidomide, on stem cell mobilization prompted us to re-evaluate the risk factors that impact mobilization, including exposure to novel induction regimens. Among 317 patients who proceeded to stem cell collection after induction therapy between 2000 and 2009, the rate of mobilization failure, defined as the inability to collect 5 × 10(6) CD34+ cells/kg following the first collection attempt, was 13%. By multivariate analysis, independent risk factors associated with mobilization failure included older age (P=0.04), lower platelet count (P=0.002) and use of single-agent G-CSF for mobilization (P<0.0001). When considering for outcome measurement stem cell collection efficiency measured by the number of CD34+ cells yielded per pheresis performed during first collection attempt, lower platelet count, use of single-agent G-CSF and older age were also associated with lower efficiency. In this population mobilized mostly with cyclophosphamide and G-CSF, the use of lenalidomide during induction was not associated with a lower stem cell collection efficiency by multivariate analysis. The data support the current International Multiple Myeloma Working Group guidelines recommending the use of cyclophosphamide and G-CSF based mobilization for patients previously exposed to lenalidomide.
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Movilización de Célula Madre Hematopoyética/métodos , Mieloma Múltiple/terapia , Adulto , Factores de Edad , Anciano , Ciclofosfamida/administración & dosificación , Recolección de Datos , Femenino , Factor Estimulante de Colonias de Granulocitos/administración & dosificación , Movilización de Célula Madre Hematopoyética/normas , Humanos , Lenalidomida , Masculino , Persona de Mediana Edad , Mieloma Múltiple/tratamiento farmacológico , Mieloma Múltiple/cirugía , Análisis Multivariante , Guías de Práctica Clínica como Asunto , Estudios Retrospectivos , Talidomida/administración & dosificación , Talidomida/análogos & derivados , Insuficiencia del Tratamiento , Resultado del TratamientoRESUMEN
To improve the efficacy of risk-adapted melphalan (MEL) in patients with amyloidosis (AL), we conducted a phase II trial using bortezomib and dexamethasone (BD) as consolidation. Forty untreated patients with renal (70%), cardiac (65%), liver/gastrointestinal (15%) or nervous system (13%) AL were assigned MEL 100, 140 or 200 mg/m(2) based on age, renal function and cardiac involvement. Hematological response was assessed at 3 months post stem cell transplant (SCT); patients with less than complete hematological response (CR) received BD consolidation. Four patients with advanced cardiac AL died within 100 days of SCT (10% treatment-related mortality). Survival at 12 and 24 months post treatment start was 88 and 82% overall and was 81 and 72% in patients with cardiac AL. At 3 months post SCT, 45% had ≥ partial response (PR) including 27% CR. Twenty-three patients received consolidation and in 86% response improved; all patients responded in one cycle. At 12 and 24 months, 79 and 60% had ≥ PR, 58 and 40% CR. Organ responses occurred in 55 and 70% at 12 and 24 months. Eight patients relapsed/progressed. One patient with serologic progression had organ impairment at time of progression. In newly diagnosed AL, BD following SCT rapidly and effectively improves responses resulting in high CR rates and maintained organ improvement.
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Amiloidosis/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Trasplante de Células Madre , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Ácidos Borónicos/administración & dosificación , Bortezomib , Dexametasona/administración & dosificación , Femenino , Humanos , Masculino , Melfalán/administración & dosificación , Persona de Mediana Edad , Pirazinas/administración & dosificaciónRESUMEN
Auto-SCT (ASCT) is widely used in first-line treatment of multiple myeloma (MM). However, most patients eventually relapse or have progression of disease (R/POD). Although precise knowledge of R/POD patterns would be important to generate evidence-based surveillance recommendations after ASCT, such data is limited in the literature, especially after introduction of the free light chain assay (FLCA). This retrospective study examined the patterns of R/POD after first-line ASCT in 273 patients, using established criteria. At the time of R/POD, only 2% of patients had no associated serological evidence of R/POD. A total of 85% had asymptomatic R/POD, first detected by serological testing, whereas 15% had symptomatic R/POD with aggressive disease, early R/POD and short survival, with poor cytogenetics and younger age identified as risk factors. Although occult skeletal lesions were found in 40% of asymptomatic patients tested following serological R/POD, yearly skeletal surveys and urine testing were poor at heralding R/POD. We found a consistent association between paraprotein types at diagnosis and R/POD, allowing informed recommendations for appropriate serological monitoring and propose a new needed criterion using FLCA for patients relapsing by FLC only. Our findings provide important evidence-based recommendations that strengthen current monitoring guidelines after first-line ASCT in MM.
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Trasplante de Células Madre Hematopoyéticas/métodos , Mieloma Múltiple/diagnóstico , Mieloma Múltiple/cirugía , Progresión de la Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Monitoreo Fisiológico , Recurrencia , Estudios Retrospectivos , Trasplante AutólogoAsunto(s)
Ácidos Borónicos/uso terapéutico , Dexametasona/uso terapéutico , Melfalán/uso terapéutico , Pirazinas/uso terapéutico , Trasplante de Células Madre , Ácidos Borónicos/administración & dosificación , Bortezomib , Terapia Combinada , Dexametasona/administración & dosificación , Humanos , Melfalán/administración & dosificación , Pirazinas/administración & dosificaciónRESUMEN
In a nation-wide registration project 38 incident cases of juvenile dermatomyositis were collected in Germany over a 2-year-period. Diagnostic methods as well as the primary treatment for these patients were recorded. Detailed information was available for 25 of these patients. Diagnostic as well as therapeutic decisions varied widely. Steroids were used in almost all of the 25 patients either as oral or as parenteral pulse therapy, additional immunosuppressive drugs were used in 52%. We plan to establish national consensus recommendations for diagnostic and therapeutic standards in JDM. Due to the rarity of JDM clinical trials will have to be performed on an international basis.
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Dermatomiositis/diagnóstico , Dermatomiositis/epidemiología , Sistema de Registros , Administración Oral , Adolescente , Corticoesteroides/administración & dosificación , Niño , Preescolar , Consenso , Estudios Transversales , Dermatomiositis/tratamiento farmacológico , Quimioterapia Combinada , Femenino , Alemania , Humanos , Inmunosupresores/administración & dosificación , Incidencia , Infusiones Intravenosas , Masculino , Guías de Práctica Clínica como Asunto , Quimioterapia por PulsoRESUMEN
The accurate measurement of T cell-associated CC chemokine receptor type 5 (CCR5) and CXC chemokine receptor type 4 (CXCR4) expression, including expression of CCR5 and CXCR4 mRNA as an immune measure of immunologic response to highly active antiretroviral therapy (HAART) and newer agents, including entry inhibitors, is essential. Previous studies have reported alterations in lymphocyte cell membrane CCR5 expression that were related to blood collection and cell separation media. Clinical trials often require the transport of specimens to central laboratories for evaluation, resulting in significant time delays between specimen procurement and analysis. This study shows that CCR5 expression on naïve and memory T cells is influenced by blood collection media and specimen age. Peripheral blood collected in Streck Vacutainer tubes containing a cell stabilizer and fixative was found to improve detection of CCR5 expression compared to specimens collected in K2 EDTA anticoagulant. The selection of flow cytometry gating strategies for the identification of naïve and memory T-helper cells can also significantly influence the sensitivity of detection of CCR5 expression. Procedural methods are described that allow for the optimal measurement of naïve and memory T-helper cell CCR5 and CXCR4 expression as well as the quantitation of CCR5 and CXCR4 mRNA.
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ARN Mensajero/análisis , Receptores CCR5/análisis , Receptores CXCR4/análisis , Citometría de Flujo/métodos , Inmunidad , Métodos , Receptores CCR5/genética , Receptores CXCR4/genética , Linfocitos T/químicaRESUMEN
The B7-CD28 immunoglobulin superfamily of costimulatory and coinhibitory ligands and their cell receptors play a critical role in modulating immune responses. Imbalances in these immune regulatory signals occur in pathological conditions characterized by chronic antigenic stimulation. Clinical studies often rely on the use of cryopreserved peripheral blood mononuclear cells (PBMC) to evaluate cellular immune responses. The impact of cryopreservation on these coinhibitory ligands and their cell receptors is unknown. In our studies, cryopreservation significantly reduced the expression of both PD-1 and PD-L1 on PBMC-derived CD3+/CD8+ T cells and CD45+/CD14+ monocytes obtained from adult control subjects. Blockade of PD-1, PD-L1, and PD-L2 using both freshly isolated and cryopreserved PBMC led to higher levels of phytohemagglutinin (PHA) and Candida-induced gamma interferon (IFN-gamma), interleukin-2 (IL-2), and tumor necrosis factor alpha (TNF-alpha) with no effect on IL-10 production. Coinhibitory signaling blockade of freshly isolated, PHA-stimulated PBMC from normal adult controls and human immunodeficiency virus (HIV)-infected subjects led to increased production of IL-4 and IL-5. Candida-stimulated PBMC preferentially induced IFN-gamma and TNF-alpha production, with reduced production of IL-2 and IL-10. This is in contrast to high levels of IFN-gamma, IL-2, and TNF-alpha production with PHA-stimulated cells. The effects of coinhibitory blockade on PHA and Candida-induced lymphoproliferation were varied, with freshly isolated PBMC from adult control subjects and HIV-infected patients yielding higher levels of lymphoproliferation in response to PD-1/PD-L1 blockade. Immune function studies employing cryopreserved cells may lead to increased T-cell effector cytolytic and regulatory immune responses.
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Antígenos CD/biosíntesis , Proteínas Reguladoras de la Apoptosis/biosíntesis , Criopreservación , Monocitos/inmunología , Monocitos/efectos de la radiación , Linfocitos T/inmunología , Linfocitos T/efectos de la radiación , Adulto , Antígeno B7-H1 , Candida/inmunología , Proliferación Celular , Citocinas/biosíntesis , Femenino , Humanos , Masculino , Persona de Mediana Edad , Fitohemaglutininas/inmunología , Receptor de Muerte Celular Programada 1 , Adulto JovenRESUMEN
BACKGROUND/AIMS: To determine the incidence, clinical presentation and histopathological profile of patients developing orbital recurrence following enucleation for retinoblastoma. METHODS: A cohort of 1674 consecutive patients undergoing enucleations between 1914 and 2006 was retrospectively reviewed to identify cases of orbital recurrence. A detailed chart review of all identified patients with orbital recurrence following enucleation was performed. The main outcome measures were histopathological features of the enucleated globe, clinical presentation, status of metastatic disease and clinical outcomes of treatment at last follow-up. RESULTS: There were 71 cases of orbital recurrence identified in the study, for an incidence of 4.2% (71 of 1674 cases). The diagnosis of orbital recurrence was made between 1 and 24 months after enucleation (mean 6 months), with 69 of the 71 patients (97%) being diagnosed within the first 12 months. Over a follow-up period of 3-208 months (mean 34.8 months), 60 of 71 patients developed metastatic disease (85%), and 53 of 71 patients died from metastatic retinoblastoma (75%). For the subgroup of cases diagnosed as having orbital recurrences after 1984, 10 of 11 patients (91%) are alive and well. CONCLUSIONS: All patients undergoing enucleation for retinoblastoma need to be followed carefully for the first 2 years after surgery for the possibility of orbital relapse. The majority of retinoblastoma patients with orbital tumour recurrence develop systemic metastatic disease, although mortalities appear to be improving in the modern era.
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Evisceración del Ojo , Neoplasias Orbitales/secundario , Neoplasias de la Retina/cirugía , Retinoblastoma/secundario , Retinoblastoma/cirugía , Biopsia , Niño , Preescolar , Coroides/patología , Estudios de Seguimiento , Humanos , Lactante , Imagen por Resonancia Magnética , Invasividad Neoplásica , Nervio Óptico/patología , Neoplasias Orbitales/mortalidad , Neoplasias Orbitales/patología , Sistema de Registros , Neoplasias de la Retina/patología , Retinoblastoma/mortalidad , Retinoblastoma/patología , Estudios Retrospectivos , Esclerótica/patologíaRESUMEN
In this study we attempted to differentiate distinct components of the saccade network, namely cortical ocular motor centers and parieto-occipital brain regions, by means of a "minimal design" approach. Using a blocked design fMRI paradigm we evaluated the BOLD changes in a 2 x 2 factorial design experiment which was performed in complete darkness: while looking straight ahead with eyes open (OPEN) or closed (CLOSED) as well as during the execution of self-initiated horizontal to-and-fro saccades with the eyes open (SACCopen) or closed (SACCclosed). Eye movements were monitored outside the scanner via electro-oculography and during scanning using video-oculography. Unintentional eye-drifts did not differ during OPEN and CLOSED and saccade frequencies, and amplitudes did not vary significantly between the two saccade conditions. The main findings of the functional imaging study were as follows: (1) Saccades with eyes open or closed in complete darkness lead to distinct differences in brain activation patterns. (2) A parieto-occipital brain region including the precuneus, superior parietal lobule, posterior part of the intraparietal sulcus (IPS), and cuneus was relatively deactivated during saccades performed with eyes closed but not during saccades with eyes open or when looking straight ahead. This could indicate a preparatory state for updating spatial information, which is active during saccades with eyes open even without actual visual input. The preparatory state is suppressed when the eyes are closed during the saccades. (3) Selected ocular motor areas, not including the parietal eye field (PEF), show a stronger activation during SACCclosed than during SACCopen. The increased effort involved in performing saccades with eyes closed, perhaps due to the unusualness of the task, may be the cause of this increased activation.
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Encéfalo/fisiología , Movimientos Oculares/fisiología , Movimientos Sacádicos/fisiología , Percepción Visual/fisiología , Adulto , Oscuridad , Femenino , Lateralidad Funcional , Humanos , Masculino , Campos VisualesRESUMEN
OBJECTIVE: This prospective blinded comparison of helical CT and helical CT arterial portography aimed to detect liver metastasis from colorectal carcinoma. METHODS AND MATERIALS: 50 patients with colorectal carcinoma were evaluated comparing helical CT with helical CT arterial portography. Each imaging study was evaluated on a 5-point ROC scale by radiologists blinded to the other imaging findings, and the results were compared, with the surgical and pathologic findings as the gold standard. RESULTS: Of the 127 lesions found at pathology identified as metastatic colorectal cancer, helical CT correctly identified 85 (69%) and CT portography 96 (76%). When subgroups with lesions <3 cm (48 patients) and patients with maximum tumor size <3 cm (18 patients) were considered, CT portography was always better than helical CT in terms of sensitivity, specificity, positive predictive value, and negative predictive value. ROC analysis adjusting for multiple lesions per patient revealed significantly greater area under the curve (AUC) for the subgroup of lesions <3 cm (CT-AUC of 77% and CT portography AUC of 81%; P = 0.002). CONCLUSIONS: For identification of large metastases, helical CT and CT portography have similar yield. However, for detection of small liver metastases, CT portography remains superior for lesion detectability.
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Neoplasias Colorrectales/diagnóstico por imagen , Neoplasias Colorrectales/patología , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/secundario , Portografía/métodos , Tomografía Computarizada Espiral , Diagnóstico Diferencial , Femenino , Estudios de Seguimiento , Hepatectomía , Humanos , Neoplasias Hepáticas/cirugía , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias/métodos , Estudios Prospectivos , Reproducibilidad de los Resultados , Sensibilidad y EspecificidadAsunto(s)
Infarto de la Arteria Cerebral Posterior/mortalidad , Infarto de la Arteria Cerebral Posterior/patología , Anciano , Edema Encefálico/complicaciones , Edema Encefálico/terapia , Progresión de la Enfermedad , Femenino , Humanos , Infarto de la Arteria Cerebral Posterior/terapia , Angiografía por Resonancia Magnética/métodos , Imagen por Resonancia Magnética/métodos , Terapia TrombolíticaRESUMEN
BACKGROUND: In hemodialysis patients, left ventricular hypertrophy (LVH) correlates with mortality. The reason for LVH in uremics is multifactorial. The primary objective of our study was to investigate the effects of a multi-interventional treatment strategy on LVH. METHODS: In 230 ambulatory patients, including patients with coronary artery disease, diabetes, diastolic and systolic dysfunction, we continued optimized cardiac therapy (beta-blockers, angiotensin-converting enzyme inhibitors and angiotensin receptor blockers) with full anemia correction by intravenous epoetin-beta. The dose of epoetin-beta for maintaining target hemoglobin (Hb) was 68 +/- 23 IU/kg/week. Serial echocardiograms were recorded every 3-6 months. The mean observation period was 4.8 +/- 1.2 years. RESULTS: Mean Hb at baseline was 11.2 +/- 2.0 versus 14.1 +/- 1.4 g/dl (p < 0.001) at study end. There was a significant reduction in left ventricular mass index (LVMI: 159 +/- 50.4 vs. 130.2 +/- 42.7 g/m(2); p < 0.001). In a subgroup of 2/3 of the patients, LVMI returned to normal (169 +/- 33 vs. 114 +/- 14 g/m2; p < 0.001). CONCLUSION: Baseline LVMI (p < 0.001), Hb increase (p < 0.03), and triple cardiac therapy (p < 0.03) were significant and independent prognostic factors for a reduction in LVMI. The annual cardiovascular mortality was 5%. Even anemia correction from 12 to 14 g/dl results in further (p < 0.001) regression of LVMI.
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Anemia/prevención & control , Bloqueadores del Receptor Tipo 1 de Angiotensina II/administración & dosificación , Inhibidores de la Enzima Convertidora de Angiotensina/administración & dosificación , Eritropoyetina/administración & dosificación , Hipertrofia Ventricular Izquierda/tratamiento farmacológico , Diálisis Renal , Uremia/terapia , Anciano , Anemia/etiología , Presión Sanguínea/efectos de los fármacos , Femenino , Humanos , Hipertrofia Ventricular Izquierda/etiología , Hipertrofia Ventricular Izquierda/mortalidad , Masculino , Persona de Mediana Edad , Proteínas Recombinantes , Uremia/complicacionesRESUMEN
We used BOLD fMRI to study the differential effects of the direction of gaze on the visual and the ocular motor systems. Fixation of a target straight ahead was compared to fixation of a target 10 degrees to the right and 10 degrees to the left from gaze straight ahead, and to eyes open in complete darkness in thirteen healthy volunteers. While retinotopic coordinates remained the same in all fixation conditions, the fixation target shifted with respect to a head-centered frame of reference. During lateral fixation, deactivations in higher-order visual areas (one ventral cluster in the lingual and fusiform gyri and one dorsal cluster in the postero-superior cuneus) and, as a trend, activations in early visual cortical areas were found predominantly in the hemisphere contralateral to the fixation target. We propose that visual processing is performed predominantly in the hemisphere contralateral to gaze direction, even during small gaze shifts into one visual hemifield. The excitability of visual neurons may be modulated depending on eye position to construct a head-centered frame of reference from a retinotopic input, thus allowing perceptual stability of space during eye movements. A further finding was that BOLD signal increases in fronto-parietal ocular motor and attentional structures were more pronounced during lateral than central fixation.
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Fijación Ocular/fisiología , Corteza Visual/fisiología , Adulto , Oscuridad , Interpretación Estadística de Datos , Femenino , Lateralidad Funcional/fisiología , Humanos , Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética , Masculino , Oxígeno/sangreRESUMEN
BACKGROUND: The purpose of this study was to retrospectively analyze the relationship between neo-adjuvant chemotherapy (NAC) and outcome in patients with high-grade extremity sarcomas. PATIENTS AND METHODS: Inclusion criteria were high-grade, deep, >5 cm extremity soft tissue sarcomas. Patients diagnosed between 1990 and 2001 were treated with surgery only (n=282) or NAC containing doxorubicin/ifosfamide/mesna (AIM) (n=74). The stratified Cox proportional hazards model was used to test the effect of NAC on disease-specific survival and recurrence while adjusting for known prognostic factors. RESULTS: NAC was associated with improved disease-specific survival for this cohort of patients (P=0.02). This overall improvement appears to be driven by the benefit of NAC on disease-specific survival for patient with tumors >10 cm. The 3-year disease-specific survival for tumors >10 cm was 0.62 (95% CI: 0.53-0.71) for patients not receiving NAC and 0.83 (95% CI: 0.72-0.95) for patients receiving NAC. CONCLUSION: NAC with AIM was associated with a significant improvement in disease-specific survival in patients with high-grade extremity soft tissue sarcomas >10 cm. These data emphasize the need for further prospective clinical studies of neo-adjuvant or adjuvant chemotherapy for patients with large high-grade extremity sarcomas.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Extremidades , Sarcoma/tratamiento farmacológico , Neoplasias de los Tejidos Blandos/tratamiento farmacológico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Quimioterapia Adyuvante , Estudios de Cohortes , Humanos , Ifosfamida/administración & dosificación , Mesna/administración & dosificación , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Estudios Retrospectivos , Sarcoma/patología , Neoplasias de los Tejidos Blandos/patología , Análisis de Supervivencia , Factores de Tiempo , Resultado del TratamientoRESUMEN
The potential for non-reciprocal Robertsonian translocations of wheat (Triticum aestivum L.) to assist in the stacking of genes was assessed from a study of their cytological and genetic behaviour. To obtain translocations, a double monosomic (3B+5A; 2n=40=19ii+2i) was crossed reciprocally with a contrasting disomic. Individuals inheriting a broken monosome were identified from the loss of one arm-specific DNA marker coupled with retention of a marker for the opposite arm. No double breaks (potential translocations) were found in 180 cross progeny recovered from pollen of the double monosomic but two instances (loss of 5AL plus 3BS; loss of 5AL plus 3BL) were found in 251 progeny recovered from ovules. Meiotic pairing and multi-color genome-specific fluorescence in situ hybridization (mcGISH) showed that each plant with a double break contained one translocated chromosome between the A and B genomes that had rejoined at the centromere and that formed a trivalent (19ii+ liii) in about 83% of PMC. Most trivalents (approximately 92%) aligned at metaphase in a 'V' configuration(alternate disjunction) while the rest aligned in linear 'I'(adjacent disjunction) or ambiguous 'L' configurations. Genetic analysis of a testcross of these 'fusion monosomics' showed that this preferential co-orientation of the trivalent influenced the assortment of the chromosome arms involved. Loci that were located in the hemizygous ends of the 'V' trivalent showed strong quasi-linkage in that most ovules from the female testcross carried relevant DNA markers either from both standard chromosomes or from neither. This shows that, in most cases, the two standard chromosomes assorted to the same pole while the fused monosome segregated to the opposite pole. For heterozygous loci (present both on the fusion monosome and the standard chromosomes) assortment was either independent or showed partial linkage to the hemizygous arm depending on the reported recombination distance from centromere. Marker assortment was further distorted in male testcrosses and in doubled haploids (made from the fusion monosomics by the maize method) by the strong selective advantage of pollen or haploids that inherited the standard chromosomes rather than the deficiencies. This genetic data shows that under the combined influence of alternate disjunction and natural selection, progeny of fusion monosomics will revert to the standard disomic arrangement, fixing the gene content of both hemizygous arms in the process. Thus, any pair of genes could be targeted for joint fixation by isolating the fusion monosome that will link them temporarily in a segregating population.
Asunto(s)
Genes de Plantas/genética , Triticum/genética , Mapeo Cromosómico , Cromosomas de las Plantas/genética , ADN de Plantas/genética , Marcadores Genéticos , Genoma de Planta , Meiosis , Metafase , Translocación Genética , Triticum/citologíaRESUMEN
Atherosclerosis related cardiovascular diseases are the leading cause of death in western societies. The clinical manifestations are chronic arterial obstructions or acute arterial occlusions in various vascular territories. The pathogenesis is only understood in part as yet. Arterial wall abnormalities, blood composition abnormalities and hemodynamic alterations are generally accepted to be causative (Virchow's triad). The key role is played by macrophages in the subendothelial space that are activated immunologically by oxidized LDL particles via the scavenger receptor pathway. Recently, endothelial dysfunction due to oxidative stress was identified as a priming factor in the course of the development of atherosclerotic plaques. Shear stress-induced microinjuries of the endothelium in hemodynamically compromised regions together with local coagulation activation associated with microinflammation of the plaque are currently thought to cause plaque rupture. This event is the reason for local clot formation and ultimate organ infarction. Treatment success is still insufficient, however some progress during the last decade is reflected by the improving outcome of atherosclerosis associated cardiovascular diseases. Evidence from clinical trials supports the efficacy of statins, antiplatelet agents, antihypertensive agents if necessary and omega-fatty acids in patients with overt atherosclerosis. The reduction of mortality achieved by those drugs amounts to: omega-fatty acids -21%, statins -16%, anti-platelet agents -14%, treatment of hypertension -13%. It is impossible to calculate the combined effect of these modalities since in each trial participants received co-medication containing agents tested in other trials.
Asunto(s)
Arteriosclerosis/tratamiento farmacológico , Arteriosclerosis/fisiopatología , Ensayos Clínicos como Asunto , Femenino , Humanos , Masculino , Resultado del TratamientoRESUMEN
Homocysteine serum levels were measured in patients with end-stage renal disease in relation to severity of renal anemia and oxidative stress parameters such as 4-hydroxynonenal (HNE) and malondialdehyde (MDA). The predialytic homocysteine serum levels of the patients are five times as high as in healthy controls. It was found that homocysteine does not correlate to hemoglobin concentration and to oxidative stress, but rather to parameters of nutrition status such as albumine concentration and protein catabolic rate. The homocysteine accumulation represents a cardiovascular risk factor which is statistically independent of oxidative stress, but dependent on nutrition or energy status in patients with chronic renal failure.