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1.
BMC Gastroenterol ; 21(1): 304, 2021 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-34332533

RESUMEN

BACKGROUND: Acute pancreatitis (AP) is an inflammatory disorder that causes a considerable economic health burden. While the overall mortality is low, around 20% of patients have a complicated course of disease resulting in increased morbidity and mortality. There is an emerging body of evidence that the microbiome exerts a crucial impact on the pathophysiology and course of AP. For several decades multiple clinical and laboratory parameters have been evaluated, and complex scoring systems were developed to predict the clinical course of AP upon admission. However, the majority of scoring systems are determined after several days and achieve a sensitivity around 70% for early prediction of severe AP. Thus, continued efforts are required to investigate reliable biomarkers for the early prediction of severity in order to guide early clinical management of AP patients. METHODS: We designed a multi-center, prospective clinical-translational study to test whether the orointestinal microbiome may serve as novel early predictor of the course, severity and outcome of patients with AP. We will recruit 400 AP patients and obtain buccal and rectal swabs within 72 h of admission to the hospital. Following DNA extraction, microbiome analysis will be performed using 3rd generation sequencing Oxford Nanopore Technologies (ONT) for 16S rRNA and metagenomic sequencing. Alpha- and beta-diversity will be determined and correlated to the revised Atlanta classification and additional clinical outcome parameters such as the length of hospital stay, number and type of complications, number of interventions and 30-day mortality. DISCUSSION: If AP patients show a distinct orointestinal microbiome dependent on the severity and course of the disease, microbiome sequencing could rapidly be implemented in the early clinical management of AP patients in the future. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04777812.


Asunto(s)
Microbiota , Pancreatitis , Enfermedad Aguda , Humanos , Estudios Multicéntricos como Asunto , Pronóstico , Estudios Prospectivos , ARN Ribosómico 16S/genética , Índice de Severidad de la Enfermedad
2.
Acta Oncol ; 60(7): 859-865, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-33646071

RESUMEN

BACKGROUND: Cancer patients are vulnerable to infections, are older and often have comorbidities in comparison to the general population, which increases the risk for severe outcomes related to COVID-19 diagnosis. METHODS: This study is a prospective, nationwide study in patients with solid cancer and SARS-CoV-2 infection included between 10 March to 15 June 2020. Patient's baseline characteristics were collected. The study's primary outcome was overall survival within 30 days of verified SARS-CoV-2 infection. Secondary outcomes were hospital admission, admission to an ICU, and need for supplemental oxygen. RESULTS: A total of 112 patients with a cancer diagnosis and verified SARS-CoV-2 infection were identified. After one month of follow up, hospitalization was required for 54% (n = 61) and 21% of the patients had died and 14 of the 23 deceased cancer patients were ≥70 years. Most patients were classified with mild COVID-19 symptoms (66%, n = 74); however, 48% (n = 23) of the ≥70-year-olds patients were classified with severe or critical COVID-19 symptoms. Among the total study population, 61% (n = 68) had comorbidities and comorbidity were more frequently observed among the deceased (91%, n = 21) and older cancer patients (≥70 years, 81%, n = 39). CONCLUSIONS: Acknowledging the low sample size in this study, our work shows that age and comorbidities, but not recent cytotoxic therapy, are associated with adverse outcomes of SARS-CoV-2 infection for patients with solid cancer. Particularly, patients with progressive disease seem to be at greater risk of a fatal outcome from COVID-19.HighlightsAge, performance status, and comorbidities are strong predictors of adverse outcome in cancer patients with SARS-CoV-2 infection.Patients with progressive cancer disease seem to be at greater risk of a fatal outcome from COVID-19.Recent cytotoxic therapy, however, did not seem to be associated with increased risk for adverse outcomes of SARS-CoV-2 infection for patients with solid cancer.


Asunto(s)
COVID-19 , Neoplasias , Anciano , Prueba de COVID-19 , Estudios de Cohortes , Dinamarca/epidemiología , Humanos , Neoplasias/epidemiología , Estudios Prospectivos , SARS-CoV-2
3.
Rhinology ; 59(1): 91-97, 2021 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-33544097

RESUMEN

OBJECTIVE: Olfactory training (OT) represents a therapeutic option for multiple etiologies of olfactory dysfunction (OD) that also benefits normosmic subjects. In this retrospective study, we report the effectiveness of OT and factors associated with relevant changes in olfactory function (OF) in large groups of normosmic participants and patients with OD, including a control group that performed no training. METHODS: This was a retrospective pooled analysis including 2 treatment cohorts of 8 previously published studies. Adult participants that either presented with the major complaint of quantitative OD or normosmic volunteers were recruited at various ENT clinics and received OT or no training. The outcome was based on changes in objective olfactory test scores after OT. RESULTS: A total of 601 patients with OD or normosmic subjects were included. OT was more effective compared to no training. No interaction was found between OT and OF. In multivariate analysis, higher baseline OF (adjusted odds ratio, aOR, 0.93) and posttraumatic (aOR, 0.29) or idiopathic OD (aOR, 0.18) compared to postinfectious causes were significantly associated with lower odds of relevant improvements in patients with OD receiving OT. Subgroup analysis of normosmic participants receiving OT further revealed a significant association of lower age and baseline olfactory function with improvements of overall OF. CONCLUSIONS: This study demonstrated that OT was more effective than no training in patients with various causes of OD. Additionally, baseline olfactory performance and etiology of OD were identified as important factors associated with relevant improvements after OT.


Asunto(s)
Trastornos del Olfato , Adulto , Humanos , Trastornos del Olfato/etiología , Estudios Retrospectivos , Olfato
4.
Rhinology ; 2020 09 09.
Artículo en Inglés | MEDLINE | ID: mdl-32901616

RESUMEN

BACKGROUND: Olfactory training (OT) represents a therapeutic option for multiple etiologies of olfactory dysfunction (OD) that also benefits normosmic subjects. In this retrospective study, we report the effectiveness of OT and factors associated with relevant changes in olfactory function (OF) in large groups of normosmic participants and patients with OD, including a control group that performed no training. METHODS: This was a retrospective pooled analysis including 2 treatment cohorts of 8 previously published studies. Adult partici- pants that either presented with the major complaint of quantitative OD or normosmic volunteers were recruited at various ENT clinics and received OT or no training. The outcome was based on changes in objective olfactory test scores after OT. RESULTS: A total of 601 patients with OD or normosmic subjects were included. OT was more effective compared to no training. No interaction was found between OT and OF. In multivariate analysis, higher baseline OF (adjusted odds ratio, aOR, 0.93) and posttraumatic (aOR, 0.29) or idiopathic OD (aOR, 0.18) compared to postinfectious causes were significantly associated with lower odds of relevant improvements in patients with OD receiving OT. Subgroup analysis of normosmic participants receiving OT further revealed a significant association of age and baseline olfactory function with improvements of overall OF. CONCLUSIONS: This study demonstrated that OT was more effective than no training in patients with various causes of OD. Additi- onally, baseline olfactory performance and etiology of OD were identified as important factors associated with relevant improve- ments after OT.

5.
HNO ; 67(4): 274-281, 2019 Apr.
Artículo en Alemán | MEDLINE | ID: mdl-30725125

RESUMEN

BACKGROUND: Dysosmia is one of the most common disorders in otorhinolaryngology. However, epidemiological data are lacking and treatment strategies are insufficiently standardized. OBJECTIVE: The aim of this study was to evaluate the frequency of causes of olfactory disorders and the different therapeutic approaches used in ENT departments in German-speaking countries. The results were also compared to findings of the survey in 2000. Furthermore, a systematic review of treatment strategies was conducted. MATERIALS AND METHODS: In 2010, a two-page survey addressing olfactory dysfunction was sent to all ENT departments in German-speaking countries. The literature review included sources such as PubMed, the Cochrane Library, and relevant guidelines. RESULTS: The diagnosis of dysosmia was made less frequently in ENT departments (decrease of 52%). The three most widely used therapeutic approaches were corticosteroids (topical and systemic) and systemic antibiotics. There is evidence in the literature showing a small to medium effect of topical steroids in sinonasal smell disorders. CONCLUSION: Since a 50% decrease in the prevalence of olfactory disturbances is unlikely, the lower patient numbers may relate to a more critical diagnosis. The use of olfactory training in clinics has increased significantly (from <6% to up to 23%). The use of topical steroids for sinonasal dysosmia is evidence based. Smell training is a safe and effective treatment strategy, especially in post-infectious and post-traumatic olfactory disorders.


Asunto(s)
Trastornos del Olfato/diagnóstico , Trastornos del Olfato/terapia , Olfato , Humanos , Esteroides/uso terapéutico , Resultado del Tratamiento
6.
Acta Anaesthesiol Scand ; 60(4): 502-12, 2016 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-26555358

RESUMEN

INTRODUCTION: The therapeutic value of intravenous immunoglobulin (IVIG) as an adjuvant therapy in sepsis remains debatable. We hypothesized that intravenous administration of BT086, a predominantly IgM IVIG solution, would improve host defense in an established rabbit model of endotoxemia and systemic sepsis. METHODS: New Zealand white rabbits were randomized into the following four groups: (1) the negative control group without lipopolysaccharide (LPS, control), (2) the positive control group with LPS infusion (LPS group), (3) the albumin-treated LPS group (ALB+LPS group), and (4) the BT086-treated LPS group (BT086 + LPS group). A standardized amount of E. coli was intravenously injected into all of the animals. The vital parameters, the concentration of E. coli in the blood and other organs, the residual granulocyte phagocytosis activity, and the levels of the inflammatory mediators were measured. Histological changes in the lung and liver tissue were examined following autopsy. RESULTS: The elimination of E. coli from the bloodstream was expedited in the BT086-treated group compared with the LPS- and albumin-treated groups. The BT086 + LPS group exhibited higher phagocytic activity of polymorphonuclear neutrophils (PMNs) than the control and ALB+LPS groups. The liver energy stores were higher in the BT086 + LPS group than in the other groups. CONCLUSION: Our data suggest that the IgM-enriched IVIG has the potential to improve host defense in a rabbit model of endotoxemia. Studies using different animal models and dosages are necessary to further explore the potential benefits of IgM-enriched IVIG solutions.


Asunto(s)
Endotoxemia/tratamiento farmacológico , Inmunoglobulina M/uso terapéutico , Inmunoglobulinas Intravenosas/uso terapéutico , Animales , Actividad Bactericida de la Sangre , Modelos Animales de Enfermedad , Endotoxemia/inmunología , Endotoxemia/fisiopatología , Hemodinámica , Neutrófilos/metabolismo , Fagocitosis , Soluciones Farmacéuticas/uso terapéutico , Conejos , Estallido Respiratorio
7.
Rhinology ; 56(1): 1-30, 2016 01 31.
Artículo en Inglés | MEDLINE | ID: mdl-28623665

RESUMEN

BACKGROUND: Olfactory dysfunction is an increasingly recognised condition, associated with reduced quality of life and major health outcomes such as neurodegeneration and death. However, translational research in this field is limited by heterogeneity in methodological approach, including definitions of impairment, improvement and appropriate assessment techniques. Accordingly, effective treatments for smell loss are limited. In an effort to encourage high quality and comparable work in this field, among others, we propose the following ideas and recommendations. Whilst the full set of recommendations are outlined in the main document, points include the following: - Patients with suspected olfactory loss should undergo a full examination of the head and neck, including rigid nasal endoscopy with small diameter endoscopes. - Subjective olfactory assessment should not be undertaken in isolation, given its poor reliability. - Psychophysical assessment tools used in clinical and research settings should include reliable and validated tests of odour threshold, and/or one of odour identification or discrimination. - Comprehensive chemosensory assessment should include gustatory screening. - Smell training can be helpful in patients with olfactory loss of several aetiologies. CONCLUSIONS: We hope the current manuscript will encourage clinicians and researchers to adopt a common language, and in so doing, increase the methodological quality, consistency and generalisability of work in this field.

8.
Laryngorhinootologie ; 93(5): 327-9, 2014 May.
Artículo en Alemán | MEDLINE | ID: mdl-24782205

RESUMEN

Providing expert opinion in the context of smell disorders is often challenging, not only with regard to general aspects of providing an expert opinion but particularly with regard to chemosensory testing. Currently there is no consensus which chemosensory test should be selected and how they should be executed. This positions paper from Committee on Olfaction and Gustation of the German Society of Otorhinolaryngology, Head and Neck Surgery aims to give concrete recommendations for chemosensory testing for providing expert opinion for smell disorders with regard to the selection and execution of these test.


Asunto(s)
Testimonio de Experto/legislación & jurisprudencia , Trastornos del Olfato/diagnóstico , Ageusia/diagnóstico , Ageusia/fisiopatología , Europa (Continente) , Potenciales Evocados Somatosensoriales/fisiología , Humanos , Trastornos del Olfato/fisiopatología , Olfatometría/métodos , Nervio Olfatorio/fisiopatología , Valor Predictivo de las Pruebas , Psicofísica , Tiempo de Reacción/fisiología
9.
Anaesthesist ; 62(6): 493-504, 2013 Jun.
Artículo en Alemán | MEDLINE | ID: mdl-23748416

RESUMEN

Inhaled anesthetics are inhaled via the lungs. They subsequently pass through the alveolocapillary membrane and diffuse into the blood to finally target the central nervous system and induce anesthesia. This principle of anesthesia induction was first described for diethylether in 1847. Nevertheless, the use of diethylether for anesthesia is obsolete and even the use of nitrous oxide (introduced for anesthesia in 1847) is declining in Germany. Almost all modern volatile anesthetics are halogenated methylethylethers in which fluorine is used as a halogen. All of these anesthetics depress myocardial contractility and induce hypotension. Depression of CO2 and hypoxia-induced respiration are other serious side effects. Further side effects are liver and kidney related but they are rare and not induced by anesthetics per se but preferentially by toxic metobolites. Another promising inhalative anesthetic is xenon which fulfils many aspects of an ideal inhalative anesthetic.


Asunto(s)
Anestésicos por Inhalación , Administración por Inhalación , Adulto , Anestesia por Inhalación , Anestésicos por Inhalación/administración & dosificación , Anestésicos por Inhalación/efectos adversos , Anestésicos por Inhalación/historia , Sistema Cardiovascular/efectos de los fármacos , Sistema Nervioso Central/efectos de los fármacos , Niño , Historia del Siglo XIX , Historia del Siglo XX , Humanos , Hipotensión/inducido químicamente , Precondicionamiento Isquémico Miocárdico , Contracción Miocárdica/efectos de los fármacos
10.
HNO ; 61(10): 843-8, 2013 Oct.
Artículo en Alemán | MEDLINE | ID: mdl-23913190

RESUMEN

Up to 80 % of children can develop otitis media with effusion (OME) between birth and school age. Responsible are longstanding impairments of tubal ventilation which are based primarily on mechanical or functional obstructions. A quarter of the subjects affected by OME show either recurrent episodes over 3 months or protracted clinical courses and in these children an extended diagnosis is required. Besides infection-related adenoid hypertrophy, the differential diagnosis should include ciliary dysfunction, chronic rhinosinusitis, craniofacial malformations, gastroesophageal reflux, tumors and cancer treatment in the nasopharynx and in particular allergies. Clinical and experimental studies have indicated that respiratory allergies promote both adenotonsillar hypertrophy as well as inflammatory alterations in the mucous membranes of the Eustachian tube and middle ear and can thus promote the formation and persistence of OME. Because of a sensitization rate of about 30% in the general population at the predilection age from 3-6 years (KiGGS study), standard diagnosis (e.g. otoscopy and audiometry) should be extended by allergy diagnostic testing, especially in cases of recurrent or prolonged courses of OME. The most common classes of medications used for childhood allergies are antihistamines and nasal steroids, which could optimize the standard treatment of OME.


Asunto(s)
Antagonistas de los Receptores Histamínicos/administración & dosificación , Hipersensibilidad/diagnóstico , Hipersensibilidad/tratamiento farmacológico , Otitis Media con Derrame/diagnóstico , Otitis Media con Derrame/prevención & control , Esteroides/administración & dosificación , Administración Intranasal , Niño , Preescolar , Diagnóstico Diferencial , Medicina Basada en la Evidencia , Humanos , Hipersensibilidad/complicaciones , Lactante , Recién Nacido , Otitis Media con Derrame/etiología , Prevención Secundaria , Resultado del Tratamiento
11.
Anaesthesist ; 60(11): 1065-80; quiz 1081-2, 2011 Nov.
Artículo en Alemán | MEDLINE | ID: mdl-22108640

RESUMEN

The demographic change is associated with an increasing number of elderly patients with serious comorbidities. The prevalence of coronary heart disease in particular increases with age and raises the risk of perioperative myocardial ischemia. In the last few years various interventions have been evaluated to lower the perioperative risk for serious cardiovascular events. This includes cardioprotective medical interventions, for example with ß-receptor blockers and statins. Current guidelines recommend that patients who are on ß-receptor blockers or statins for chronic treatment of cardiovascular diseases should continue this medication throughout the perioperative period. Myocardial conditioning has been assessed to be effective under numerous experimental conditions and clinical trials have also provided evidence for myocardial protection by conditioning. Besides ischemic and anesthetic-induced preconditioning the noninvasive technique of remote preconditioning offers interesting possibilities, especially for patients with serious comorbidities; however, large scale randomized clinical multicentre trials are still needed. Regarding cardioprotective effectiveness, the clinical data for regional anesthesia are very heterogeneous; nevertheless regional anesthesia is very effective in postoperative pain therapy. Therefore regional anesthesia should be used as a part of multimodal therapy concepts to lower the risk of perioperative cardiovascular events.


Asunto(s)
Cardiotónicos/uso terapéutico , Cardiopatías/prevención & control , Atención Perioperativa/métodos , Antagonistas Adrenérgicos beta/uso terapéutico , Anestesia , Antioxidantes/uso terapéutico , Arteriosclerosis/tratamiento farmacológico , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Precondicionamiento Isquémico Miocárdico , Isquemia Miocárdica/prevención & control , Daño por Reperfusión Miocárdica/prevención & control , Apoyo Nutricional , Medición de Riesgo
12.
Eur J Surg Oncol ; 33(3): 358-63, 2007 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-17157472

RESUMEN

AIM: A consensus treatment strategy for advanced cervical metastatic head and neck squamous cell carcinoma has not been established. The aim of this retrospective study was to investigate the outcome of these patients uniformely using a strategy which consists of surgery for the primary tumor and the neck metastases followed by postoperative radio(chemo)therapy. METHODS: We included a selected series of 518 patients with previously untreated head and neck squamous cell carcinoma. The overall survival (OS), the disease specific survival (DSS), the disease free survival (DFS), the local control (LC) and regional control (RC) estimates were calculated. The statistical relationship of various clinical and histopathological variables on the above mentioned estimates were analyzed. RESULTS: The overall survival probability was 73.2% for pN0 stage, 43% for pN>1 stages and 31% for pN2c/pN3 stages. The pN stage significantly influenced the survival probabilities in oropharyngeal (p=0.0001) and laryngeal tumors (p<0.0001) in univariate analyses. In multivariate analysis, age, pT stage, pN stage, M stage, and extranodal spreading were independent risk factors for decreased disease-specific survival. CONCLUSIONS: We could show that pN stage is an important independent prognostic factor in head and neck cancer. The presented multimodal treatment protocol provides excellent oncological outcomes and should therefore be standard of care for patients with operable advanced cervical metastatic head and neck squamous cell carcinoma.


Asunto(s)
Carcinoma de Células Escamosas/terapia , Neoplasias de Cabeza y Cuello/terapia , Carcinoma de Células Escamosas/patología , Terapia Combinada , Femenino , Neoplasias de Cabeza y Cuello/patología , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Modelos de Riesgos Proporcionales , Dosificación Radioterapéutica , Estudios Retrospectivos , Tasa de Supervivencia , Resultado del Tratamiento
13.
Rhinol Suppl ; 54(26): 1-30, 2017 03.
Artículo en Inglés | MEDLINE | ID: mdl-29528615

RESUMEN

Background: Olfactory dysfunction is an increasingly recognised condition, associated with reduced quality of life and major health outcomes such as neurodegeneration and death. However, translational research in this field is limited by heterogeneity in methodological approach, including definitions of impairment, improvement and appropriate assessment techniques. Accordingly, effective treatments for smell loss are limited. In an effort to encourage high quality and comparable work in this field, among others, we propose the following ideas and recommendations. Whilst the full set of recommendations are outlined in the main document, points include the following: • Patients with suspected olfactory loss should undergo a full examination of the head and neck, including rigid nasal endoscopy with small diameter endoscopes. • Subjective olfactory assessment should not be undertaken in isolation, given its poor reliability. • Psychophysical assessment tools used in clinical and research settings should include reliable and validated tests of odour threshold, and/or one of odour identification or discrimination. • Comprehensive chemosensory assessment should include gustatory screening. • Smell training can be helpful in patients with olfactory loss of several aetiologies. Conclusions: We hope the current manuscript will encourage clinicians and researchers to adopt a common language, and in so doing, increase the methodological quality, consistency and generalisability of work in this field.


Asunto(s)
Trastornos del Olfato/diagnóstico , Trastornos del Olfato/terapia , Humanos , Pruebas Neuropsicológicas , Olfatometría , Percepción Olfatoria , Calidad de Vida
14.
Rhinology ; 44(2): 135-9, 2006 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-16792173

RESUMEN

HYPOTHESIS: We investigated whether olfactory dysfunction following infections of the upper respiratory tract (post-URTI) has an incidence matching the seasonality of URTIs. STUDY DESIGN: Retrospective study. METHODS: In total, 457 patients (126 male, 331 female) with post-URTI olfactory loss were examined during a 6-year-period (1999-2004). Their records were assessed for age, sex, and time of onset of the disease. The severity of olfactory dysfunction was assessed using the "Sniffin' Sticks" (odour threshold, odour discrimination, and odour identification). RESULTS: Incidence of post-URTI olfactory dysfunction exhibited seasonal fluctuations with deviations from the winter seasonality of URTIs. The overall incidence of the disease differed significantly between months. March (12.7%) and May (12.6%) were the months with the highest incidence of the disease throughout the year. The lowest incidence was observed in September (5.6%). Significant differences were found between these months and months with a high incidence of URTIs. DISCUSSION: The peak incidence of post-URTI olfactory loss in March may be explained by the high incidence of influenza at this time. However, it is unclear why the incidence of the disease presents a second peak in May, when the incidence of respiratory viruses is relatively low. Climate conditions at this time might play a role in the susceptibility of the nasal epithelia towards certain viral infections, e.g. parainfluenza type III. CONCLUSION: Post-URTI olfactory dysfunction exhibits spring seasonality with peaks in March and May and possible causative factors being influenza and parainfluenza viruses (type III), respectively.


Asunto(s)
Trastornos del Olfato/epidemiología , Trastornos del Olfato/etiología , Infecciones del Sistema Respiratorio/complicaciones , Estaciones del Año , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Estudios Retrospectivos
15.
J Hosp Infect ; 8(3): 217-23, 1986 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-2878025

RESUMEN

Intravenous administration sets were changed at varying time intervals between every 24 h and 120 h in 387 patients. The rates of intraluminal contamination of the cannulae and of local inflammation were measured in relation to the time interval between changing sets. There was no correlation between phlebitis and intraluminal contamination, but a significant association was found between phlebitis and fever, infusion of potassium at greater than 10 mmol l-1, Venflon type 140 and infusion of blood or intralipid. No correlation was found between septicaemia and intraluminal contamination of the infusion systems. Contamination of cannulae increased slightly with time, but this was not statistically significant. We conclude that there will be no clinical benefit by daily changing of administration sets, compared with changing up to every fifth day.


Asunto(s)
Contaminación de Equipos , Infusiones Intravenosas/instrumentación , Flebitis/etiología , Transfusión Sanguínea , Emulsiones Grasas Intravenosas/administración & dosificación , Femenino , Fiebre/etiología , Humanos , Masculino , Potasio/administración & dosificación , Estudios Prospectivos , Distribución Aleatoria , Factores de Tiempo
16.
Eur J Pharm Biopharm ; 58(1): 7-14, 2004 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-15207532

RESUMEN

Pulmonary drug delivery is increasingly appreciated as a route of administration for systemically acting proteins and peptides. A respirable particle size of the drug is a key requirement, but the fragile nature of many proteins may be a limitation for the application of conventional production processes. The aim of this study was to examine the effect of different micronisation processes on the degradation and aerodynamic properties of the GnRH-antagonist cetrorelix in order to enable its application by a dry powder inhaler (Novolizer). A modified pearl mill was used for milling in fluid propellant. Furthermore, a spray drying procedure was established using a novel process of atomisation and drying. Adhesive mixtures of lactose and 5-20% of micronised cetrorelix-acetate were prepared. Analysis by laser light scattering, HPLC, Karl Fischer, cascade impactor and scanning electron microscopy were performed to characterise the manufactured powders. Both micronisation procedures succeeded in producing small range particle size distributions, suitable for deep lung deposition (D50 = 1.6 microm for milling and 3.3 microm for spray drying). The pearl milled cetrorelix showed promising results when delivered by the Novolizer: a reproducible and highly efficient dispersion of the drug was achieved (around 60% of aerosolised drug < 5 microm). The spray dried drug was not suitable when processed as adhesive mixture.


Asunto(s)
Sistemas de Liberación de Medicamentos/métodos , Microesferas , Péptidos/administración & dosificación , Péptidos/química , Administración por Inhalación , Tamaño de la Partícula , Polvos
17.
Laryngoscope ; 110(7): 1215-21, 2000 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-10892699

RESUMEN

OBJECTIVES/HYPOTHESIS: In carcinoma in situ (CIS) tumors malignant cells have not penetrated the basement membrane and therefore have no metastatic potential. Treatment strategies of CIS are topics of ongoing discussion. The aim of this study was to evaluate long-term results of CO2 laser therapy in laryngeal CIS. METHODS: From 1986 to 1995, 29 patients with glottic CIS with a minimum follow-up of 2 years were treated initially with transoral CO2 laser surgery and were included is this series. RESULTS: A complete removal of the tumor was possible with superficial laser cordectomy in 21 patients and with subligamental laser cordectomy in 8 cases. There was no tumor-related death in this series. Repeated laser resections were performed in four patients for local recurrences. No patient required total laryngectomy or radiotherapy during a follow-up ranging from 25 to 143 months. CONCLUSIONS: Local control rates presented in this study are superior to those previously reported with conventional surgery and similar to those after radiotherapy. The ultimate rate of larynx preservation was seven times higher than reported after radiotherapy. Our results add further support to the observation that laser surgery is the best treatment option for CIS of the larynx. Based on the material of this study, recommended treatment for CIS is CO2 laser resection in combination with a meticulous follow-up for early recognition of local recurrence.


Asunto(s)
Dióxido de Carbono , Carcinoma in Situ/cirugía , Glotis/cirugía , Neoplasias Laríngeas/cirugía , Terapia por Láser/métodos , Anciano , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Orofaringe , Cuidados Posoperatorios , Complicaciones Posoperatorias , Cuidados Preoperatorios , Índice de Severidad de la Enfermedad , Resultado del Tratamiento , Trastornos de la Voz/diagnóstico , Calidad de la Voz
18.
Laryngoscope ; 110(6): 1012-7, 2000 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-10852523

RESUMEN

OBJECTIVES: Recently published data suggest a prognostic value of immunohistochemical proliferation markers for limited laryngeal carcinoma. Previous studies have reported contrasting findings on this issue. In this context, different treatment modalities may be responsible for contradictory findings. To study the relationship between proliferative activity--expressed by the immunohistochemical labeling index of proliferation-associated markers Ki-67 (MIB1), Lewis-X (LeuM1), and proliferating cell nuclear antigen (PCNA) and by p53 status--and treatment failure in a matched-pair study on recurrent and nonrecurrent T1 and T2 glottic carcinoma having received primary transoral laser surgery. METHODS: Twenty-one patients with tumor recurrence were randomly selected and matched with 26 patients with nonrecurrent disease regarding histopathological grading and age. MIB1 staining was used to determine the Ki-67 labeling index, and LeuM1 staining for detecting the Lewis-X antigen; immunohistochemistry determined the p53 status and PCNA labeling index. RESULTS: The Ki-67 labeling index was significantly (P = .001) higher in tumors from patients who had treatment failure (mean = 20.02%) than in patients who did not fail treatment ("nonfailures") (mean = 9.95%). Carcinoma with a Ki-67 (MIB1) labeling index above the median (15%) of the general study population showed a mean time to relapse of 23 months (n = 21), compared with 50 months for cases (n = 26) below the median (P = .016). PCNA labeling index correlated less impressively with tumor recurrence (mean = 28.59% for treatment failures, mean = 21.75% for nonfailures, P = .022). Positive detection of the Lewis-X antigen was significantly associated with recurrence (P = .015) and time to relapse (P = .006). Status of p53 was not a significant prognostic factor. CONCLUSION: The Ki-67 (MIB1) labeling index may be associated with early relapse of limited laryngeal carcinoma treated with transoral laser surgery. Since the prognostic relevance of Ki-67 seems to be different for radiological and surgical concepts of treatment, Ki-67 might become useful as criterion of therapy selection. The Lewis-X antigen, for the first time used on laryngeal carcinoma, seems to be a strong prognostic marker deserving further investigations.


Asunto(s)
Antígenos de Superficie/metabolismo , Carcinoma de Células Escamosas/metabolismo , Genes p53 , Antígeno Ki-67/metabolismo , Neoplasias Laríngeas/metabolismo , Recurrencia Local de Neoplasia/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Antígenos de Neoplasias/metabolismo , Carcinoma de Células Escamosas/genética , Femenino , Estudios de Seguimiento , Humanos , Inmunohistoquímica , Neoplasias Laríngeas/genética , Antígeno Lewis X , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/genética , Estadificación de Neoplasias , Pronóstico , Antígeno Nuclear de Célula en Proliferación/genética , Antígeno Nuclear de Célula en Proliferación/metabolismo
19.
Otolaryngol Head Neck Surg ; 121(5): 633-8, 1999 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-10547485

RESUMEN

BACKGROUND AND OBJECTIVE: Acute epiglottitis, bacterial tracheitis, and severe viral laryngotracheobronchitis continue to cause life-threatening airway obstruction in children. The aim of this retrospective study was to evaluate deficiencies in treatment, to clarify the role of airway endoscopy, and to identify current reasons for fatalities in these diseases. MATERIALS AND PATIENTS: During the observation period from 1980 to 1996, we identified 61 patients treated in the pediatric intensive care unit of the University Hospital of Cologne for severe inflammatory airway obstruction. RESULTS: Critical points in the appropriate airway management were (1) the confirmation of the admission diagnosis, (2) whether an artificial airway or rigid tracheobronchoscopy was required; and (3) appropriate timing of extubation. Since 1989 airway evaluation with flexible or small, rigid endoscopes was used to confirm the diagnosis and to determine the appropriate management. Endoscopic findings were extremely helpful to decide not to intubate and to monitor in the pediatric intensive care unit first. Three patients with acute epiglottitis died after out-of-hospital cardiorespiratory arrest. CONCLUSION: Endoscopy should be a part of every established treatment protocol of childhood stridor. The most decisive factor to decrease mortality seems to be timely presentation to a referral center.


Asunto(s)
Obstrucción de las Vías Aéreas/terapia , Cuidados Críticos , Ruidos Respiratorios/etiología , Infecciones del Sistema Respiratorio/terapia , Obstrucción de las Vías Aéreas/diagnóstico , Obstrucción de las Vías Aéreas/mortalidad , Bronquitis/diagnóstico , Bronquitis/mortalidad , Bronquitis/terapia , Broncoscopía , Niño , Preescolar , Epiglotitis/diagnóstico , Epiglotitis/mortalidad , Epiglotitis/terapia , Femenino , Humanos , Lactante , Laringitis/diagnóstico , Laringitis/mortalidad , Laringitis/terapia , Laringoscopía , Masculino , Infecciones del Sistema Respiratorio/diagnóstico , Infecciones del Sistema Respiratorio/mortalidad , Estudios Retrospectivos , Traqueítis/diagnóstico , Traqueítis/mortalidad , Traqueítis/terapia , Resultado del Tratamiento
20.
Otolaryngol Head Neck Surg ; 120(4): 517-23, 1999 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-10187944

RESUMEN

BACKGROUND: The aim of this prospective study was to evaluate the efficacy of a combined (local and systemic) steroid therapy on the extent of chronic polypoid rhinosinusitis and patient symptoms. METHODS AND PATIENTS: Subjects of this study were 20 patients with severe chronic polypoid rhinosinusitis with total or subtotal narrowing of the all sinuses. A nasal budesonide spray (2 x 0.1 mg/day) and an oral fluocortolone medication with a daily reduction during a 12-day period (total dose: 560 mg = group 1) and a 20-day period (total dose: 715 mg = group 2), respectively, were administered. Before and after the steroid treatment we evaluated the extent of the sinusitis with MRI and patient symptoms with symptom-related questionnaires. RESULTS: A significant reduction (> 30%) of the chronic polypoid rhinosinusitis was observed in 50% of MRI findings. The steroid effect on polypoid masses was heterogeneous in different anatomic areas (maxillary sinus 40%, anterior ethmoid 19%, posterior ethmoid 33%, sphenoidal sinus 61%, frontal sinus 46%). Most sinusitis-related symptoms were distinctly diminished in most patients (80%). No major side effects were observed. CONCLUSIONS: A combined short-term steroid therapy is highly effective in chronic polypoid rhinosinusitis, reducing the mucosal inflammation mainly in the large sinuses and reducing the incidence of symptoms significantly. However, this therapy was insufficient in the anterior ethmoid and cannot replace the current surgical treatment concept of the osteomeatal complex in CPR. The indication for such a short-term steroid therapy is the preoperative treatment. It facilitates functional endoscopic sinus surgery by reducing the extent of surgical procedures, the time, and thereby the risks of sinus surgery.


Asunto(s)
Antiinflamatorios/uso terapéutico , Budesonida/uso terapéutico , Fluocortolona/uso terapéutico , Glucocorticoides/uso terapéutico , Rinitis/tratamiento farmacológico , Sinusitis/tratamiento farmacológico , Administración por Inhalación , Administración Oral , Adulto , Anciano , Antiinflamatorios/administración & dosificación , Budesonida/administración & dosificación , Enfermedad Crónica , Quimioterapia Combinada , Femenino , Fluocortolona/administración & dosificación , Glucocorticoides/administración & dosificación , Humanos , Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Pólipos , Estudios Prospectivos , Rinitis/diagnóstico , Rinitis/patología , Sinusitis/diagnóstico , Sinusitis/patología
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