RESUMEN
According to research children living with HIV experience elevated levels of depression, anxiety, ADHD and disruptive behavioural disorders. Although South Africa's paediatric population that is infected with the human immunodeficiency virus (HIV) is the largest worldwide, little research has been conducted on their mental health challenges. However, attributing high levels of mental health problems solely to their HIV status can be problematic as there may be other contributory factors. This research explored the mental health problems of HIV-infected children and compared these to the mental health problems of their HIV-unaffected peers from similar backgrounds. Data was gathered from two samples of child and caregiver pairs. HIV-infected children (aged 6-12 years) and their caregivers/mothers (n = 54) were recruited from the Kalafong paediatric clinic where they received medical treatment and routine ART. A comparison group of 113 HIV-uninfected children and their uninfected mothers were recruited from primary care clinics in the same community. Caregivers completed the Child Behaviour Checklist (CBCL) to assess children's mental health. Children completed the Self-Description Questionnaire (SDQ-I) and the Revised Children's Manifest Anxiety Scale (RCMAS). The scores of the psychometric sub-scales of the two groups were compared using parametric and non-parametric statistics. HIV-infected children experienced more somatic and affective problems, physiological anxiety, less ADHD and lower self-esteem than HIV-uninfected children in the comparison group, while controlling for age differences. The high levels of mental health problems of both groups of children may be attributed to similar difficult socio-economic circumstances. The fact that most infected children were not aware of their HIV-status could have influenced the results. Mental health services should not be limited to HIV-infected children but should form part of all health care services.
Asunto(s)
Infecciones por VIH/epidemiología , Infecciones por VIH/psicología , Trastornos Mentales/epidemiología , Autoimagen , Trastornos de Ansiedad/epidemiología , Trastorno por Déficit de Atención con Hiperactividad/epidemiología , Cuidadores , Estudios de Casos y Controles , Niño , Depresión/epidemiología , Femenino , Humanos , Masculino , Salud Mental , Trastornos del Humor/epidemiología , Madres , Sudáfrica/epidemiología , Encuestas y CuestionariosRESUMEN
OBJECTIVES: Shared decision making (SDM) is a process in which patients and their doctors collaborate in choosing a suitable treatment option by incorporating patient values and preferences, as well as the best available evidence. Particularly in vascular surgery, several conditions seem suitable for SDM because there are multiple treatment options. The objective of this study was to assess the degree of SDM behaviour in vascular surgery. METHODS: Vascular surgeons of four Dutch hospitals selected consultations with patients who were facing a treatment decision. Immediately after the consultation, patients and surgeons completed the (subjective) SDM Q-9 and SDM Q-doc questionnaires respectively, to appreciate the perceived level of SDM behaviour. Two evaluators independently and objectively rated SDM behaviour in the audiotaped consultations, using the Observing Patient Involvement (OPTION-12) scale. RESULTS: Nine vascular surgeons and three vascular surgeons in training conducted 54 consultations. The patients' median SDM Q-9 score was high, 93% (IQR 79-100%), and 16/54 (29.6%) of them gave the maximum score. The surgeons' median score was also high, 84% (IQR 73-92%), while 4/54 (7.4%) gave the maximum score. In contrast, mean OPTION score was 31% (SD 11%). Surgeons hardly ever asked the patients for their preferred approach to receive information, whether they had understood the provided information, and how they would like to be involved in SDM. CONCLUSIONS: Currently, objective SDM behaviour among vascular surgeons is limited, even though the presented disorders allow for SDM. Hence, SDM in vascular surgical consultations could be improved by increasing the patients' and surgeons' awareness and knowledge about the concept of SDM.
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Actitud del Personal de Salud , Conducta de Elección , Conocimientos, Actitudes y Práctica en Salud , Participación del Paciente , Relaciones Médico-Paciente , Cirujanos/psicología , Procedimientos Quirúrgicos Vasculares , Concienciación , Comunicación , Humanos , Países Bajos , Percepción , Derivación y Consulta , Medición de Riesgo , Factores de Riesgo , Encuestas y Cuestionarios , Resultado del Tratamiento , Procedimientos Quirúrgicos Vasculares/efectos adversosRESUMEN
OBJECTIVES: In acute type B aortic dissection (ABAD) a patent false lumen portends a poor outcome. Patent branch vessels originating from the false lumen in a type B aortic dissection are assumed to contribute to persistent blood flow and patent false lumen. Therefore, the morphologic changes of the false lumen generated by different outflow rates in an in vitro model were investigated. METHODS: An artificial dissection was created in two ex vivo porcine aortas. A thin cannula was placed in the false lumen, simulating a branch vessel originating from it. The aorta was positioned in a validated in vitro circulatory system with physiological pulsatile flow (1,500-2,700 mL/minute) and pressure characteristics (130/70 mm Hg). The cannula was attached to a small silicone tube with an adjustable valve mechanism. Three different valve settings were used for creating outflow from the false lumen (fully closed, opened at 50%, and fully opened at 100%). Measurements of lumen areas and flow rates were assessed with time-resolved magnetic resonance imaging. In order to study reproducibility, the experiment was performed twice in two different porcine aortas with a similar morphology. RESULTS: Increasing antegrade outflow through the branch vessel of the false lumen resulted in a significant (p < .01) increase of the mean false lumen area at the proximal and distal location in both models. The distal false lumen expanded up to 107% in the case of high outflow via the false lumen through the branch vessel. CONCLUSIONS: Increasing antegrade outflow through a branch vessel originating from the false lumen when no distal re-entry tear is present results in an expansion of the cross sectional false lumen area.
Asunto(s)
Aneurisma de la Aorta/patología , Disección Aórtica/patología , Vasos Sanguíneos/patología , Modelos Cardiovasculares , Animales , Aneurisma de la Aorta/cirugía , Aortografía/métodos , Velocidad del Flujo Sanguíneo/fisiología , Imagen por Resonancia Magnética/métodos , Reproducibilidad de los Resultados , Porcinos , Procedimientos Quirúrgicos Vasculares/métodosRESUMEN
PURPOSE: Genetic research has opened up possibilities for identification of persons with an increased susceptibility for occupational disease. However, regulations considering the ethical issues that are inevitably associated with the use of genetic tests for susceptibility for occupational diseases are scarce. We investigated whether opinions of an intended stakeholder group, that is, student nurses, are sufficiently addressed by existing recommendations. METHODS: Attitudes and opinions of Dutch student nurses toward a genetic test for susceptibility to occupational contact eczema were studied in a qualitative setup using focus groups, interviews and electronic questionnaires. The results were compared with guidelines and recommendations extracted from the literature. RESULTS: Sixty-nine percent of the student nurses said they would partake in a genetic test for susceptibility to occupational contact eczema when available. Concerns were expressed regarding the difficulty of interpreting test results, the utility of the test result in practice and the necessity of genetic tests for non-severe diseases. For the issue of privacy and confidentiality, the students expressed few worries and much confidence. The existing guidelines largely covered the students' opinions. Still, the data emphasized the need for good individual risk communication both before and after testing, taking into account that the test concerns susceptibility. CONCLUSIONS: Comparing the students' statements with the issues addressed by the guidelines, we conclude that the guidelines should pay more attention to risk communication and practical advice accompanying the test results.
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Actitud del Personal de Salud , Dermatitis por Contacto/genética , Dermatitis Profesional/genética , Predisposición Genética a la Enfermedad , Pruebas Genéticas/ética , Estudiantes de Enfermería/psicología , Adolescente , Adulto , Comunicación , Confidencialidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Salud Laboral/ética , Guías de Práctica Clínica como Asunto , Factores de Riesgo , Adulto JovenRESUMEN
BACKGROUND: Atopic dermatitis (AD) and loss-of-function mutations in the filaggrin gene (FLG) are both associated with chronic irritant contact dermatitis (ICD). As FLG mutations also are a major risk factor for AD, it is not clear whether FLG mutations are an independent risk factor for ICD or whether the risk is mediated by AD. OBJECTIVES: To investigate the relative contribution and interaction of FLG mutations and AD in German patients with occupational ICD and controls (vocational school apprentices). METHODS: A total of 634 patients and 393 controls were genotyped for R501X, 2282del4, R2447X and S3247X. Current or past flexural eczema was used as an indicator of AD. RESULTS: FLG mutations were found in 15·9% of the patients with ICD and 8·3% of the controls, with a crude odds ratio (OR) of 2·09 [95% confidence interval (CI) 1·33-3·28] for the combined genotype. The adjusted OR for FLG mutations, corrected for AD, was 1·62 (95% CI 1·01-2·58). Subjects with AD were at approximately three times higher risk of developing ICD than controls (OR 2·89; 95% CI 2·09-3·99). There was no evidence of an interaction between these two risk factors. CONCLUSIONS: Our results indicate that both FLG mutations and AD increase the risk of ICD. Individuals with concurrent FLG mutations and AD are at the highest risk of developing ICD.
Asunto(s)
Dermatitis Atópica/genética , Dermatitis Irritante/genética , Dermatitis Profesional/genética , Proteínas de Filamentos Intermediarios/genética , Mutación/genética , Adulto , Edad de Inicio , Femenino , Proteínas Filagrina , Predisposición Genética a la Enfermedad/genética , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Factores de RiesgoRESUMEN
Infection of endovascular abdominal aneurysm stent grafts is an uncommon but known complication. Inoculation with bacteria of the endovascular abdominal aneurysm stent graft during the actual implantation, in the periprocedural hospitalization or later due to an aortoenteric fistula, has been described in the literature. We report a case of endovascular abdominal aortic aneurysm stent graft infection occurring 40 months after implantation in a patient doing well up to an episode of urosepsis. In conclusion, we postulate that poor intraluminal healing of stent grafts, as observed in several explant studies, may result in a higher susceptibility to episodes of bacteremia than prosthetic vascular grafts inserted during open repair. We therefore consider the administration of prophylactic antibiotics in patients with endovascular stent grafts during periods with a likelihood of bacteremia.
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Aneurisma de la Aorta Abdominal/cirugía , Implantación de Prótesis Vascular/efectos adversos , Prótesis Vascular/efectos adversos , Procedimientos Endovasculares/efectos adversos , Infecciones Relacionadas con Prótesis/microbiología , Stents/efectos adversos , Anciano de 80 o más Años , Antibacterianos/uso terapéutico , Aortografía/métodos , Biopsia , Implantación de Prótesis Vascular/instrumentación , Remoción de Dispositivos , Procedimientos Endovasculares/instrumentación , Humanos , Masculino , Valor Predictivo de las Pruebas , Infecciones Relacionadas con Prótesis/diagnóstico , Infecciones Relacionadas con Prótesis/terapia , Reoperación , Factores de Riesgo , Tomografía Computarizada por Rayos X , Resultado del Tratamiento , Infecciones Urinarias/complicaciones , Infecciones Urinarias/diagnóstico , Infecciones Urinarias/tratamiento farmacológico , Infecciones Urinarias/microbiologíaRESUMEN
This study examined the experiences and perceived benefits of support group participation among HIV-infected women in South Africa. From a qualitative analysis of responses, key psychological processes through which support groups are potentially beneficial were identified. These processes included: identification; modeling; acceptance; and empowerment. The participants' consequent life changes were explored in order to associate these processes with the positive outcomes of support group participation. Through understanding the relationship between the psychological processes within a support group setting and the potential benefits, and by targeting these processes in the development and implementation of future support group interventions, a framework is provided for achieving positive outcomes associated with support group participation.
RESUMEN
We present a patient with Wegener's granulomatosis (WG) with involvement of the abdominal aorta, testis, peripheral nerve system, and skin. A 51-year-old man presented at our outpatient clinic with lower back pain. He had a history of smoking, hypertension, and an embryonal carcinoma of the left testis, treated 13 years ago with orchidectomy and chemotherapy. One month earlier, he underwent a partial orchidectomy of the right testis due to testicular swelling. Abdominal computed tomography showed a 3.8 cm wide aneurysm of the distal part of the aorta with inflammation. One week later he was admitted to the hospital with numbness of his hands and feet. Physical examination showed signs of peripheral microemboli. Serological laboratory tests revealed elevated antineutrophil cytoplasmic antibody titers with positive reactions against proteinase-3, indicating Wegener's disease. The chest X-ray was normal. Pathological examination of the right testis showed necrotizing vasculitis of a small artery. He was treated with cyclophosphamide and prednisolone. WG with extrapulmonary involvement occurs infrequently, and reports of manifestations of WG in aorta, testis, the peripheral nerve system, and skin are even more uncommon. Small- and medium-vessel vasculitis can precede large-vessel vasculitis or occur in the absence of small-vessel involvement. Therefore, WG should be included in the work-up of large-vessel vasculitis, which can give rise to periaortic inflammation.
Asunto(s)
Aneurisma de la Aorta Abdominal/etiología , Granulomatosis con Poliangitis/diagnóstico , Orquitis/etiología , Adulto , Anciano , Aneurisma de la Aorta Abdominal/diagnóstico por imagen , Aneurisma de la Aorta Abdominal/tratamiento farmacológico , Aortografía/métodos , Ciclofosfamida/administración & dosificación , Quimioterapia Combinada , Femenino , Granulomatosis con Poliangitis/complicaciones , Granulomatosis con Poliangitis/tratamiento farmacológico , Humanos , Hipoestesia/etiología , Inmunosupresores/administración & dosificación , Técnicas In Vitro , Masculino , Persona de Mediana Edad , Orquitis/tratamiento farmacológico , Orquitis/patología , Prednisolona/administración & dosificación , Quimioterapia por Pulso , Testículo/patología , Tomografía Computarizada por Rayos X , Resultado del Tratamiento , Adulto JovenRESUMEN
HIV/AIDS-related stigma threatens to undermine interventions to prevent and treat HIV/AIDS. To address stigma in a South African community, a thorough understanding of the nature of stigma in the specific cultural context is needed. The goals of this research were to assess the level of stigmatising attitudes among members of a community, compare this to the level of stigma that is perceived to exist within the community and determine to what extent stigmatising attitudes are affected by socio-demographic characteristics, HIV-related experience and cultural beliefs. A questionnaire was completed by 1077 respondents in key areas in two communities in Tshwane, South Africa. The questionnaire included an assessment of HIV-related experience, HIV-knowledge, personal stigma and perceptions of stigma within the community. The findings indicate that the level of personal stigma was significantly lower than that perceived to be present in the community. Respondents who were more stigmatising were older, male, less educated and less knowledgeable about HIV. They were less likely to know someone with HIV and had more traditional cultural viewpoints. While socio-demographic and cultural factors are difficult to change, efforts aimed at increasing people's knowledge and experience of the epidemic occurring in their community could change the level of stigmatising attitudes within their community. Such efforts could have potential benefits in addressing the epidemic and providing greater support for those with HIV.
Asunto(s)
Infecciones por VIH/psicología , Prejuicio , Opinión Pública , Estereotipo , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Infecciones por VIH/etnología , Conocimientos, Actitudes y Práctica en Salud , Humanos , Masculino , Persona de Mediana Edad , Factores Socioeconómicos , Sudáfrica/etnología , Encuestas y Cuestionarios , Adulto JovenRESUMEN
OBJECTIVES: To compare the diagnostic and therapeutic confidence, patient outcome and costs between MRA and DSA as the initial diagnostic imaging test, in patients with symptomatic arterial disease of the leg. DESIGN: Randomised controlled diagnostic trial. MATERIALS AND METHODS: Patients were randomly allocated to MRA (n=97) or DSA (n=100). Primary outcomes were: ability to make treatment plan and patients satisfaction. Secondary endpoints were: type of treatment and costs. RESULTS: A treatment plan was determined for each included patient. Additional imaging was necessary in 11% of patients in the MRA group compared to 10% in the DSA group (p=0.5). 84% of the patients who received MRA judged the diagnostic work up as comfortable compared to 57% who had DSA (p=0.013). Within 4 months of randomization 30 patients in the MRA group compared to 34 patients in de DSA group underwent operative procedures; 39 versus 36 patients respectively underwent angioplasty. The mean total in-hospital costs during the first 4 months were euro4768,- in the MRA group compared to euro4697,- in the DSA group (95% CI of difference -1331;1472). CONCLUSIONS: In patients with peripheral arterial disease of the leg an adequate treatment plan can be made with MRA. This diagnostic strategy was experienced as more comfortable and less painful compared to DSA. Total diagnostic and treatment costs of both strategies were comparable.
Asunto(s)
Angiografía de Substracción Digital , Angiografía por Resonancia Magnética , Enfermedades Vasculares Periféricas/diagnóstico por imagen , Anciano , Medios de Contraste , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
A 57-year-old male had a thoraco-abdominal aortic aneurysm that was increasing in diameter, accompanied by pain in the right lower abdomen and groin. Ten years earlier he had had a dissecting thoraco-abdominal aneurysm that extended from the left subclavian artery to the aortic bifurcation. A CT-scan revealed further growth of the aneurysm. He was treated by an open and an endovascular operation. The distal aorta was replaced by a bifurcation prosthesis via a laparotomy, with 2 other bifurcation prostheses to 2 mesenteric and 2 renal arteries. In a second session, a carotid-subclavian bypass was constructed and the aorta was reinforced by an endograft from the left subclavian artery to the bifurcation prosthesis. Postoperatively he suffered a transient ischaemic attack, hypertension, pneumonia, and vocal cord paresis. At follow-up 1.5 years later, the patient was free of symptoms, with the exception of slight hoarseness during forced speech, and the aneurysm was totally under control. This procedure may be an alternative to the classical thoracophrenicolaparotomy.
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Aneurisma de la Aorta Abdominal/cirugía , Aneurisma de la Aorta Torácica/cirugía , Implantación de Prótesis Vascular , Embolización Terapéutica/métodos , Humanos , Masculino , Persona de Mediana Edad , Retratamiento , Tomografía Computarizada por Rayos X , Resultado del TratamientoRESUMEN
The implementation and evaluation of a peer education and support programme in secondary schools to prevent and reduce high-risk sexual behaviour amongst adolescents is discussed.The aims of the programme were to provide accurate information about HIV/AIDS; discuss and reconsider peer group norms; and establish support for learners. In the programme that was implemented in 13 secondary schools in Tshwane; South Africa; peer educators were identified; trained and supported to implement the programme in their schools with the assistance of a teacher and postgraduate students as facilitators. Peer educators organised HIV awareness activities; facilitated class discussions on risk behaviour and gender relationships; and supported learners in solving personal problems. Process evaluation included weekly reports and focus group discussions with peer educators and teachers. A quasiexperimental design involving an experimental and control group; as well as pre- and post-assessments; was used to evaluate the impact of the programme on psychological well-being; personal control; school climate and reported high-risk behaviour of learners aged between 13 and 20 years.The results showed that the percentage of learners in the experimental group who were sexually experienced remained unchanged over the time period of 18 months. In contrast; a significantly increased percentage of learners in the control group were sexually experienced after the same time period.The control group also perceived more of their friends to be sexually experienced. No differences were reported in condom use in either of the groups.The findings of this study suggest that peer education can contribute to a delayed onset of sexual activity; and can therefore contribute to the prevention of HIV/AIDS amongst adolescents
Asunto(s)
VIH , Síndrome de Inmunodeficiencia Adquirida/educación , Síndrome de Inmunodeficiencia Adquirida/prevención & control , Adolescente , Instituciones Académicas , Conducta SexualRESUMEN
Exposure to endotoxin at sewage treatment plants is associated with an increased prevalence of work-related symptoms in sewage workers. Since cleaning activities are regarded as an important determinant of endotoxin exposure, workers' endotoxin exposure levels during different cleaning activities were compared in an experimental setting. Variables considered were water used (tap water, surface water or effluent), water pressure (low or high pressure, and a fire hose with the mouth open or obstructed), presence of mechanical ventilation and the distance between the worker and the object to be cleaned (concentration gradient). Experimental cleaning scenarios were defined, during which endotoxin exposure was measured with personal and stationary air sampling. Data were statistically analyzed with mixed effects models. The water used for cleaning appeared to have a large influence on endotoxin exposure, especially the use of effluent, which caused a factor 2.4 increase in exposure. Use of high pressure did not significantly add to the exposure. Use of a fire hose with fully opened mouth (spout opening) led to a 3-fold decrease in exposure when compared with a partially obstructed mouth. The presence of mechanical ventilation decreased endotoxin concentration in a room, provided that the capacity of the ventilation system was sufficient. The worker's distance to the object that was cleaned did not significantly influence exposure.
Asunto(s)
Endotoxinas/administración & dosificación , Tareas del Hogar/métodos , Exposición Profesional/análisis , Aguas del Alcantarillado , Endotoxinas/análisis , Monitoreo del Ambiente/métodos , Humanos , VentilaciónRESUMEN
OBJECTIVES: The purpose of this study is to determine the accuracy of measuring pressure with a fluid filled pressure device (needle) and a non-fluid filled pressure device (catheter) inside a thrombosed aneurysmal sac after exclusion from circulation by endovascular grafting. METHODS: In a static environment, consisting of a syringe to which a pressure monitoring kit was connected, experiments were performed to study the influence of the type of device (either needle or catheter) and the effect of the characteristics of the medium on the accuracy and reproducibility of pressure measurements. The pressures obtained with the needle in the different kinds of media were compared with those obtained in blood. Similar experiments were performed using a pressure catheter. Subsequently, pressure measurements were performed in a dynamic and physiological environment. This environment consisted of an artificial circulation in which an aneurysm, constructed of porcine aorta and filled with human aortic thrombus, was mounted. The pressures were compared and analyzed by Bland-Altman plots. RESULTS: Under static conditions, the pressure levels obtained by a needle in blood, starch solution and thrombus were similar. Under identical conditions, pressures obtained by a catheter in starch solution were significant lower than the pressures measured in blood (P<0.05). Under dynamic pressure conditions the reproducibility of pressures obtained with the needle inserted in the human thrombus was very poor. CONCLUSION: A needle pressure measuring device, inserted into media like human fibrin thrombus, does not yield accurate and reproducible results. A catheter with a tip-sensor rather than a needle is superior to study the pressure in the aneurysm sac after EVAR.
Asunto(s)
Aneurisma/fisiopatología , Monitores de Presión Sanguínea , Presión Sanguínea/fisiología , Aneurisma/cirugía , Animales , Determinación de la Presión Sanguínea/instrumentación , Cateterismo , Modelos Animales de Enfermedad , Humanos , Manometría/instrumentación , Modelos Cardiovasculares , Agujas , Reproducibilidad de los Resultados , PorcinosRESUMEN
To assess long-term effects and side-effects of fluticasone propionate (FP), a 2-yr study was performed, comparing a step-down dose approach (1,000 microg.day(-1), with reductions every 2 months to 500, 200 and 100 microg.day(-1) for the remainder of the study) versus a constant dose (200 microg.day(-1)). In 55 children with chronic persistent asthma, aged 6-10 yrs, airways hyperresponsiveness (AHR) and systemic side-effects (height, bone parameters and adrenal cortical function) were assessed at predetermined intervals in a double-blind prospective 2-yr study. AHR improved after 4 months treatment with 1,000 microg.day(-1) FP followed by 500 microg.day(-1), without significant differences during long-term treatment between the two approaches. Dose-dependent reduction of growth velocity, adrenal cortical function and biochemical bone turnover was found during therapy with 1,000 and 500 microg.day(-1) FP when compared with 200 microg.day(-1). In conclusion, doses of 1,000 and 500 microg.day(-1) fluticasone propionate are associated with marked reductions of growth velocity, bone turnover and adrenal cortical function. However, conventional doses (< or =200 microg.day(-1) fluticasone propionate) appear to be safe in the long-term management of childhood asthma. From a safety point of view, high doses of fluticasone propionate should only be prescribed in exceptions, e.g. in persistent severe asthma.
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Androstadienos/administración & dosificación , Androstadienos/efectos adversos , Asma/tratamiento farmacológico , Broncodilatadores/administración & dosificación , Broncodilatadores/efectos adversos , Corteza Suprarrenal/efectos de los fármacos , Androstadienos/uso terapéutico , Densidad Ósea/efectos de los fármacos , Huesos/efectos de los fármacos , Hiperreactividad Bronquial/tratamiento farmacológico , Broncodilatadores/uso terapéutico , Niño , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Femenino , Fluticasona , Crecimiento/efectos de los fármacos , Humanos , Masculino , Estudios ProspectivosRESUMEN
BACKGROUND: Asthma is characterized by eosinophilic airways inflammation with elevated levels of IL-4, IL-5 and sICAM-1, and reduced levels of IL-10 and IFN-gamma. Inhaled corticosteroids powerfully reduce airways inflammation. OBJECTIVE: To investigate if eosinophil counts, serum eosinophilic cationic protein (ECP) and sICAM-1 levels, as well as serum and production of cytokines (IL-4, IL-5, IL-10, IFN-gamma) by peripheral blood monocytes (PBMCs) are useful markers to monitor therapy with inhaled fluticasone propionate (FP) in asthmatic children. METHODS: In a double-blind, 1-year study, 55 asthmatic children (aged 6-10 years) stopped inhaled corticosteroids for a mean period of 24 days and were randomized to receive either FP 200 microg/day (constant dose group), or a starting dose of FP 1000 microg/day with two monthly reductions to 500, 200 and 100 microg/day (stepdown group). Hyper-responsiveness, symptom scores and blood sampling were performed at 2-month intervals. RESULTS: Symptoms and hyper-responsiveness improved significantly in both treatment groups after reintroduction of FP. Eosinophil counts decreased significantly more during the first 2 months of FP in the stepdown group than in the constant dose group (P = 0.03). We found a trend towards a dose-dependent response in changes of eosinophil counts and serum ECP levels during treatment. Serum IL-4 and IL-5 levels were undetectable in the majority of children. No significant effect of the dose of FP on the release of IL-4, IL-5, IL-10 or IFN-gamma by Con A stimulated PBMCs was found. sICAM-1 levels did not significantly differ at any time point between the two groups. CONCLUSION: Serum ECP as well as peripheral blood eosinophils, cytokine production by PBMCs and sICAM-1 levels are insensitive markers in titrating and monitoring therapy with inhaled corticosteroids over a wide dose range in childhood asthma.
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Androstadienos/administración & dosificación , Antiinflamatorios/administración & dosificación , Asma/tratamiento farmacológico , Citocinas/sangre , Ribonucleasas , Administración por Inhalación , Administración Tópica , Asma/inmunología , Asma/fisiopatología , Biomarcadores/sangre , Proteínas Sanguíneas/análisis , Hiperreactividad Bronquial , Moléculas de Adhesión Celular/sangre , Niño , Método Doble Ciego , Esquema de Medicación , Proteínas en los Gránulos del Eosinófilo , Eosinófilos , Femenino , Fluticasona , Glucocorticoides , Humanos , Inmunoglobulina E/sangre , Interferón gamma/sangre , Interleucina-10/sangre , Interleucina-4/sangre , Interleucina-5/sangre , Recuento de Leucocitos , MasculinoRESUMEN
BACKGROUND: During the baseline period of a clinical trial comparing different dosage schedules of inhaled steroids, asthmatic children (aged 6-10 years) were expected to meet the inclusion criterion of airways hyper-responsiveness (PD(20) methacholine < 80 micro g) after withdrawal of inhaled corticosteroids for 2-8 weeks. However, many children failed to do so. OBJECTIVE: It has been shown that young wheezing children may outgrow their symptoms. We investigated if differences between children with and without airways hyper-responsiveness after withdrawal of inhaled corticosteroids were compatible with differences between transient and persistent wheezers found in other studies. METHODS: Seventy-eight children entered the study, of which 41 developed airways hyper- responsiveness after withdrawal of inhaled corticosteroids, and 37 did not. These two groups of children were compared with respect to differences in demographic, clinical, and immunological features (IL-4, IL-5, IL-10, and IFN-gamma produced by Con A stimulated peripheral mononuclear cells (PBMCs) and serum IL-4, IL-5 and soluble intercellular adhesion molecule-1 (sICAM-1)). RESULTS: Hyper-responsive children had more atopic features (positive RAST, high IgE, eczema), lower levels of FEV1 and lower concentrations of sICAM-1 than non-hyper-responsive children. Apart from a borderline significantly higher IL-4 production in the hyper-responsive group, other immunologic parameters were comparable. Multivariate logistic regression analysis showed that high serum IgE, low FEV1, and low sICAM-1 levels were independently associated with the presence of airways hyper-responsiveness after stopping inhaled corticosteroids. Atopy was associated with higher concentrations of IL-4 in the hyper-responsive group. CONCLUSION: After withdrawal of inhaled corticosteroids many children previously diagnosed with asthma did not develop airways hyper-responsiveness. We conclude that hyper-responsive children share features with persistent wheezers as found in previous studies, whereas the non-hyper- responsive children may represent transient wheezers.
Asunto(s)
Asma/fisiopatología , Hiperreactividad Bronquial , Animales , Animales Domésticos , Asma/tratamiento farmacológico , Asma/inmunología , Peso al Nacer , Lactancia Materna , Pruebas Respiratorias , Broncoconstrictores , Moléculas de Adhesión Celular/sangre , Niño , Concanavalina A , Femenino , Glucocorticoides/uso terapéutico , Humanos , Hipersensibilidad Inmediata/complicaciones , Hipersensibilidad Inmediata/inmunología , Interferón gamma/sangre , Interleucina-10/sangre , Interleucina-4/sangre , Interleucina-5/sangre , Leucocitos Mononucleares/inmunología , Modelos Logísticos , Activación de Linfocitos , Masculino , Cloruro de Metacolina , Óxido Nítrico/análisis , Pruebas de Función Respiratoria , Fumar , Procedimientos InnecesariosRESUMEN
Dose-dependent effects of inhaled corticosteroids have been described. Although it has been advised to start treatment with inhaled corticosteroids with a high dose tapering off subsequently (stepdown approach), no clinical studies have assessed this strategy. We compared two different dosage schedules of inhaled fluticasone propionate (FP) in chronic persistent childhood asthma with respect to efficacy (airways hyperresponsiveness [PD(20)], lung function, exhaled nitric oxide [eNO]) and safety (height). During this double-blind study, children with asthma (aged 6-10 yr) were randomized to receive either FP 200 microg/d (constant dose approach) or to start with 1000 microg/d with two monthly reductions to 500, 200, and 100 microg/d (stepdown approach). PD(20) improved in both approaches during treatment with FP, with a significantly better PD(20) after 2 mo of 1000 microg/d followed by 500 microg/d in the stepdown approach versus 200 microg/d in the constant dose approach. No significant differences in PD(20) or other efficacy parameters were found after 1 yr. Changes in standing height were similar in both treatment approaches. This study showed no superior clinical effect of a stepdown approach compared with a constant dose strategy of FP for 1 yr in children with chronic persistent asthma.
Asunto(s)
Androstadienos/administración & dosificación , Antiasmáticos/administración & dosificación , Antiinflamatorios/administración & dosificación , Asma/tratamiento farmacológico , Estatura/efectos de los fármacos , Hiperreactividad Bronquial/tratamiento farmacológico , Volumen Espiratorio Forzado/efectos de los fármacos , Administración por Inhalación , Androstadienos/farmacología , Antiasmáticos/farmacología , Antiinflamatorios/farmacología , Asma/diagnóstico , Asma/metabolismo , Asma/fisiopatología , Pruebas Respiratorias , Hiperreactividad Bronquial/diagnóstico , Hiperreactividad Bronquial/metabolismo , Hiperreactividad Bronquial/fisiopatología , Pruebas de Provocación Bronquial , Broncoconstrictores , Niño , Enfermedad Crónica , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Fluticasona , Humanos , Cloruro de Metacolina , Óxido Nítrico/análisis , Factores de TiempoRESUMEN
The feasibility of moderately severe airway hyperresponsiveness (AH) was examined as an inclusion criterion for clinical trials in asthmatic children. During the baseline period of a long-term clinical trial in asthmatic children, maintenance therapy with fluticasone (200 microg x day(-1)) was stopped for a maximum of 8 weeks and methacholine challenges were performed at 2-week intervals or earlier if the patients' condition deteriorated. Patients were eligible to continue the study if the provocative dose of methacholine causing a 20% fall in forced expired volume in one second (FEV1) (PD20) was <80 microg. Fifty-one per cent of the children did not develop a PD20 < 80 microg after withdrawal of fluticasone. Patients with or without a PD20 <80 microg did not differ in duration of asthma, duration of treatment, or peak flow variation. Patients with a PD20 <80 microg had higher levels of total and specific immunoglobulin-E, and lower levels of FEV1 and mean maximal expiratory flow than patients with a PD20 > or = 80 microg. Forty-four per cent of the patients with a PD20 > or = 80 microg did not have any symptoms during the wash-out period and 39% of these patients remained free from symptoms during one year follow-up. The results of this study suggest that recruiting asthmatic children for clinical trials may be difficult if airways hyperresponsiveness is used as the sole inclusion criterion.
Asunto(s)
Asma/tratamiento farmacológico , Hiperreactividad Bronquial/tratamiento farmacológico , Pruebas de Provocación Bronquial , Ensayos Clínicos como Asunto , Selección de Paciente , Androstadienos/administración & dosificación , Androstadienos/efectos adversos , Asma/diagnóstico , Hiperreactividad Bronquial/diagnóstico , Niño , Estudios de Factibilidad , Femenino , Fluticasona , Humanos , Cuidados a Largo Plazo , Masculino , Cloruro de Metacolina , Síndrome de Abstinencia a Sustancias/diagnósticoRESUMEN
OBJECTIVE: Dysfunctional ejaculation and, to a lesser extent, dysfunctional erection caused by disruption of efferent sympathetic pathways is a common complication after aortoiliac reconstruction surgery. The aim was to give an anatomic motivation for a nerve-preserving approach on the basis of right-sided unilateral disruption of lumbar splanchnic nerves. METHODS: Anatomic and microscopic analysis of preaortic and para-aortic retroperitoneal regions in human cadavers was performed. Anatomic analysis was conducted of two aortoiliac reconstruction operations performed on human cadavers; one was performed according to a single-blind procedure, the second with a modified procedure. RESULTS: The lumbar splanchnic nerves supplying the superior hypogastric plexus from the right side were found to be less voluminous than the left-sided ones. The superior hypogastric plexus was found slightly shifted to the left of the midsagittal plane across the abdominal aorta and its bifurcation. Microscopic analysis revealed a thin fascia between the aorta and the subperitoneal tissue compartment. This fascia was used as a plain of dissection to mobilize the preaortic nerve-plexuses without damage from the aortic wall. Analysis of the specimens operated on showed a significant difference in nerve disruption. The standard procedure caused total disruption of the superior hypogastric plexus and extensive disruption of the inferior mesenteric plexus. The modified procedure only caused right-sided unilateral disruption of lumbar splanchnic nerves. CONCLUSION: The autonomic nerves supplying the bladder neck, the vas deferens, and the prostate are closely related to the abdominal aorta and its bifurcation. Right-sided unilateral disruption of lumbar splanchnic nerves without further damage to nervous structures would ensure at least one functional sympathetic pathway remaining after aortoiliac reconstruction surgery.