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1.
BMC Nephrol ; 20(1): 231, 2019 06 25.
Artículo en Inglés | MEDLINE | ID: mdl-31238898

RESUMEN

BACKGROUND: Maintenance dialysis is a costly and resource intense activity. In Australia, inadequate health infrastructure and poor access to technically skilled staff can limit service provision in remote areas where many Aboriginal dialysis patients live. With most studies based on urban service provision, there is little evidence to guide service development. However permanent relocation to an urban area for treatment can have significant social and financial impacts that are poorly quantified. This study is part of a broader project to quantify the costs and benefits of dialysis service models in urban and remote locations in Australia's Northern Territory (NT). METHODS: We undertook a micro-costing analysis of dialysis service delivery costs in urban, rural and remote areas in the NT from the payer perspective. Recurrent maintenance costs (salaries, consumables, facility management and transportation) as well as capital costs were included. Missing and centralised costs were standardised; results were inflated to 2017 values and reported in Australian dollars. RESULTS: There was little difference between the average annual cost for urban and rural services with respective median costs of $85,919 versus $84,629. However remote service costs were higher ($120,172 - $124,492), driven by higher staff costs. The inclusion of capital costs did not add substantially to annual costs. Annual home haemodialysis costs ($42,927) were similar to other jurisdictions despite the significant differences in program delivery and payment of expenses not traditionally borne by governments. Annual peritoneal dialysis costs ($58,489) were both higher than home and in-centre haemodialysis by recent national dialysis cost studies. CONCLUSION: The cost drivers for staffed services were staffing models and patient attendance rates. Staff salaries and transport costs were significantly higher in remote models of care. Opportunities to reduce expenditure exist by encouraging community supported services and employing local staff. Despite the delivery challenges of home haemodialysis including high patient attrition, the program still provides a cost benefit compared to urban staffed services. The next component of this study will examine patient health service utilisation and costs by model of care to provide a more comprehensive analysis of the overall cost of providing services in each location.


Asunto(s)
Análisis Costo-Beneficio , Atención a la Salud/economía , Costos de la Atención en Salud , Servicios de Salud/economía , Diálisis Renal/economía , Población Rural , Análisis Costo-Beneficio/tendencias , Atención a la Salud/tendencias , Costos de la Atención en Salud/tendencias , Servicios de Salud/tendencias , Humanos , Northern Territory/epidemiología , Diálisis Renal/tendencias , Población Rural/tendencias
2.
Nephrology (Carlton) ; 23(1): 37-45, 2018 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-29250918

RESUMEN

OBJECTIVE: To describe the detailed associations of albuminuria among a contemporary cohort of Aboriginal and Torres Strait Islander people to inform strategies for chronic kidney disease prevention and management. METHODS: A cross-sectional analysis of Indigenous participants of the eGFR Study. MEASURES: Clinical, biochemical and anthropometric measures were collected (including body-circumferences, blood pressure (BP); triglycerides, HbA1c, liver function tests, creatinine; urine- microscopic-haem, albumin: creatinine ratio (ACR), prescriptions- angiotensin converting enzyme inhibitor or angiotensin receptor II antagonist (ACEI/ARB). Albuminuria and diabetes were defined by an ACR>3.0 mg/mmol, and HbA1c≥48 mmol/mol or prior history respectively. Waist: hip ratio (WHR), and estimated glomerular filtration rate (eGFR) were calculated. ACR was non-normally distributed; a logarithmic transformation was applied (in base 2), with each unit increase in log2-albuminuria representing a doubling of ACR. RESULTS: 591 participants were assessed (71% Aboriginal, 61.6% female, mean age 45.1 years, BMI 30.2 kg/m2 , WHR 0.94, eGFR 99.2 ml/min/1.73m2 ). The overall prevalence of albuminuria, diabetes, microscopic-haem and ACEI/ARB use was 41.5%, 41.5%, 17.8% and 34.7% respectively; 69.3% of adults with albuminuria and diabetes received an ACEI/ARB. Using multivariable linear regression modelling, the potentially modifiable factors independently associated with log2-albuminuria were microscopic-haem, diabetes, WHR, systolic BP, alkaline phosphatase (all positive) and eGFR (inverse). CONCLUSION: Albuminuria is associated with diabetes, central obesity and haematuria. High ACEI/ARB prescribing for adults with diabetes and albuminuria was observed. Further understanding of the links between fat deposition, haematuria and albuminuria is required.


Asunto(s)
Albuminuria/etnología , Tasa de Filtración Glomerular , Riñón/fisiopatología , Nativos de Hawái y Otras Islas del Pacífico , Adiposidad , Adulto , Albuminuria/diagnóstico , Albuminuria/fisiopatología , Bloqueadores del Receptor Tipo 1 de Angiotensina II/uso terapéutico , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Australia/epidemiología , Presión Sanguínea , Distribución de Chi-Cuadrado , Estudios Transversales , Diabetes Mellitus/etnología , Diabetes Mellitus/fisiopatología , Femenino , Hematuria/etnología , Hematuria/fisiopatología , Humanos , Hipertensión/etnología , Hipertensión/fisiopatología , Modelos Lineales , Masculino , Persona de Mediana Edad , Análisis Multivariante , Obesidad Abdominal/etnología , Obesidad Abdominal/fisiopatología , Prevalencia , Factores de Riesgo
3.
Diabet Med ; 31(7): 829-38, 2014 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-24598003

RESUMEN

AIMS: It has been proposed that the Chronic Kidney Disease Epidemiology Collaboration formula estimates glomerular filtration rate more accurately than the Modification of Diet in Renal Disease formula. With the very high incidence of diabetes and end-stage kidney disease in Indigenous Australians, accurate estimation of glomerular filtration rate is vital in early detection of kidney disease. We aimed to assess the performance of the Chronic Kidney Disease Epidemiology Collaboration, Modification of Diet in Renal Disease and Cockcroft-Gault formulas in Indigenous Australians with and without diabetes. METHODS: Indigenous Australians with (n = 224) or without (n = 340) Type 2 diabetes had a reference glomerular filtration rate measure using plasma disappearance of iohexol (measured glomerular filtration rate) over 4 h. Serum creatinine was measured by an enzymatic method. Performance was assessed by bias (measured glomerular filtration rate - estimated glomerular filtration rate) and accuracy (percentage of estimated glomerular filtration rate within 30% of measured glomerular filtration rate). RESULTS: The median measured glomerular filtration rate (interquartile range) in participants with or without diabetes was 97 (68-119) and 108 (90-122) ml min(-1)  1.73 m(-2) , respectively. The Chronic Kidney Disease Epidemiology Collaboration formula had smaller bias and greater accuracy than the Modification of Diet in Renal Disease and Cockcroft-Gault formulas overall, for participants both with and without diabetes. However, for estimated glomerular filtration rate > 90 ml min(-1)  1.73 m(-2) , the Chronic Kidney Disease Epidemiology Collaboration formula had greater bias in participants with diabetes, underestimating measured glomerular filtration rate by 7.4 vs. 1.0 ml min(-1)  1.73 m(-2) in those without diabetes. The Chronic Kidney Disease Epidemiology Collaboration formula was less accurate across the whole range of estimated glomerular filtration rates in participants with vs. those without diabetes (87.1% vs. 93.3%). CONCLUSIONS: The Chronic Kidney Disease Epidemiology Collaboration formula outperforms the Modification of Diet in Renal Disease and Cockcroft-Gault formulas overall in Indigenous Australians with and without diabetes. However, the Chronic Kidney Disease Epidemiology Collaboration formula has greater bias in people with diabetes compared with those without diabetes, especially in those with normal renal function.


Asunto(s)
Creatinina/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Dieta para Diabéticos/métodos , Yohexol , Nativos de Hawái y Otras Islas del Pacífico , Insuficiencia Renal Crónica/diagnóstico , Australia/epidemiología , Diabetes Mellitus Tipo 2/epidemiología , Diabetes Mellitus Tipo 2/fisiopatología , Diagnóstico Precoz , Femenino , Tasa de Filtración Glomerular , Servicios de Salud del Indígena , Humanos , Pruebas de Función Renal/métodos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Insuficiencia Renal Crónica/epidemiología , Insuficiencia Renal Crónica/fisiopatología , Reproducibilidad de los Resultados
5.
Intern Med J ; 42(9): 1043-6, 2012 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-24020342

RESUMEN

Secondary amyloidosis (AA) is an established consequence of many chronic inflammatory conditions. In the developed world, it is most often the result of rheumatological disease. However, the relative frequency of underlying causes may be different in indigenous populations. We present a case series of three remote-living, Indigenous Australians found to have pathologically confirmed amyloidosis and renal impairment at diagnosis. The presence of an underlying inflammatory condition was unclear in two cases. The remaining case had established bronchiectasis and suffered rapidly progressive renal impairment at a young age.


Asunto(s)
Amiloidosis/etnología , Nativos de Hawái y Otras Islas del Pacífico , Adolescente , Adulto , Amiloidosis/etiología , Amiloidosis/metabolismo , Bronquiectasia/complicaciones , Comorbilidad , Progresión de la Enfermedad , Susceptibilidad a Enfermedades , Femenino , Humanos , Inflamación/complicaciones , Fallo Renal Crónico/etnología , Fallo Renal Crónico/etiología , Fallo Renal Crónico/metabolismo , Masculino , Proteína Amiloide A Sérica/metabolismo
6.
J Exp Med ; 190(11): 1697-710, 1999 Dec 06.
Artículo en Inglés | MEDLINE | ID: mdl-10587360

RESUMEN

The cause of many autoimmune and inflammatory diseases is unresolved, although dysregulated production of tumor necrosis factor (TNF) family members appears to be important in many cases. BAFF, a new member of the TNF family, binds to B cells and costimulates their growth in vitro. Mice transgenic for BAFF have vastly increased numbers of mature B and effector T cells, and develop autoimmune-like manifestations such as the presence of high levels of rheumatoid factors, circulating immune complexes, anti-DNA autoantibodies, and immunoglobulin deposition in the kidneys. This phenotype is reminiscent of certain human autoimmune disorders and suggests that dysregulation of BAFF expression may be a critical element in the chain of events leading to autoimmunity.


Asunto(s)
Autoanticuerpos/sangre , Enfermedades Autoinmunes/inmunología , Linfocitos B/inmunología , Enfermedades Linfáticas/inmunología , Proteínas de la Membrana/genética , Proteínas de la Membrana/inmunología , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/inmunología , Animales , Anticuerpos Antinucleares/sangre , Enfermedades Autoinmunes/genética , Enfermedades Autoinmunes/patología , Factor Activador de Células B , Citometría de Flujo , Humanos , Inmunoglobulina A/sangre , Inmunoglobulina G/sangre , Inmunoglobulina M/sangre , Inmunoglobulinas/metabolismo , Riñón/inmunología , Riñón/patología , Cinética , Recuento de Leucocitos , Pulmón/inmunología , Enfermedades Linfáticas/genética , Enfermedades Linfáticas/patología , Ratones , Ratones Transgénicos , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Factor Reumatoide/sangre , Linfocitos T/inmunología
7.
J Exp Med ; 189(11): 1747-56, 1999 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-10359578

RESUMEN

Members of the tumor necrosis factor (TNF) family induce pleiotropic biological responses, including cell growth, differentiation, and even death. Here we describe a novel member of the TNF family, designated BAFF (for B cell activating factor belonging to the TNF family), which is expressed by T cells and dendritic cells. Human BAFF was mapped to chromosome 13q32-34. Membrane-bound BAFF was processed and secreted through the action of a protease whose specificity matches that of the furin family of proprotein convertases. The expression of BAFF receptor appeared to be restricted to B cells. Both membrane-bound and soluble BAFF induced proliferation of anti-immunoglobulin M-stimulated peripheral blood B lymphocytes. Moreover, increased amounts of immunoglobulins were found in supernatants of germinal center-like B cells costimulated with BAFF. These results suggest that BAFF plays an important role as costimulator of B cell proliferation and function.


Asunto(s)
Linfocitos B/inmunología , Proteínas de la Membrana/fisiología , Receptores del Factor de Necrosis Tumoral/fisiología , Factor de Necrosis Tumoral alfa/fisiología , Secuencia de Aminoácidos , Animales , Factor Activador de Células B , Linfocitos B/citología , Secuencia de Bases , División Celular , Línea Celular , Mapeo Cromosómico , Cromosomas Humanos Par 13/genética , Clonación Molecular , Cartilla de ADN/genética , Células Dendríticas/inmunología , Humanos , Ligandos , Activación de Linfocitos , Proteínas de la Membrana/genética , Ratones , Datos de Secuencia Molecular , Receptores del Factor de Necrosis Tumoral/genética , Homología de Secuencia de Aminoácido , Linfocitos T/inmunología , Factor de Necrosis Tumoral alfa/genética
8.
Lancet ; 371(9618): 1098-107, 2008 Mar 29.
Artículo en Inglés | MEDLINE | ID: mdl-18355913

RESUMEN

BACKGROUND: The international standard radiotherapy schedule for early breast cancer delivers 50 Gy in 25 fractions of 2.0 Gy over 5 weeks, but there is a long history of non-standard regimens delivering a lower total dose using fewer, larger fractions (hypofractionation). We aimed to test the benefits of radiotherapy schedules using fraction sizes larger than 2.0 Gy in terms of local-regional tumour control, normal tissue responses, quality of life, and economic consequences in women prescribed post-operative radiotherapy. METHODS: Between 1999 and 2001, 2215 women with early breast cancer (pT1-3a pN0-1 M0) at 23 centres in the UK were randomly assigned after primary surgery to receive 50 Gy in 25 fractions of 2.0 Gy over 5 weeks or 40 Gy in 15 fractions of 2.67 Gy over 3 weeks. Women were eligible for the trial if they were aged over 18 years, did not have an immediate reconstruction, and were available for follow-up. Randomisation method was computer generated and was not blinded. The protocol-specified principal endpoints were local-regional tumour relapse, defined as reappearance of cancer at irradiated sites, late normal tissue effects, and quality of life. Analysis was by intention to treat. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN59368779. FINDINGS: 1105 women were assigned to the 50 Gy group and 1110 to the 40 Gy group. After a median follow up of 6.0 years (IQR 5.0-6.2) the rate of local-regional tumour relapse at 5 years was 2.2% (95% CI 1.3-3.1) in the 40 Gy group and 3.3% (95% CI 2.2 to 4.5) in the 50 Gy group, representing an absolute difference of -0.7% (95% CI -1.7% to 0.9%)--ie, the absolute difference in local-regional relapse could be up to 1.7% better and at most 1% worse after 40 Gy than after 50 Gy. Photographic and patient self-assessments indicated lower rates of late adverse effects after 40 Gy than after 50 Gy. INTERPRETATION: A radiation schedule delivering 40 Gy in 15 fractions seems to offer rates of local-regional tumour relapse and late adverse effects at least as favourable as the standard schedule of 50 Gy in 25 fractions.


Asunto(s)
Neoplasias de la Mama/radioterapia , Radioterapia de Alta Energía/normas , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/cirugía , Fraccionamiento de la Dosis de Radiación , Femenino , Humanos , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Modelos de Riesgos Proporcionales , Calidad de Vida , Dosificación Radioterapéutica , Análisis de Supervivencia , Factores de Tiempo , Resultado del Tratamiento , Reino Unido
9.
Lancet Oncol ; 9(4): 331-41, 2008 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-18356109

RESUMEN

BACKGROUND: The international standard radiotherapy schedule for breast cancer treatment delivers a high total dose in 25 small daily doses (fractions). However, a lower total dose delivered in fewer, larger fractions (hypofractionation) is hypothesised to be at least as safe and effective as the standard treatment. We tested two dose levels of a 13-fraction schedule against the standard regimen with the aim of measuring the sensitivity of normal and malignant tissues to fraction size. METHODS: Between 1998 and 2002, 2236 women with early breast cancer (pT1-3a pN0-1 M0) at 17 centres in the UK were randomly assigned after primary surgery to receive 50 Gy in 25 fractions of 2.0 Gy versus 41.6 Gy or 39 Gy in 13 fractions of 3.2 Gy or 3.0 Gy over 5 weeks. Women were eligible if they were aged over 18 years, did not have an immediate surgical reconstruction, and were available for follow-up. Randomisation method was computer generated and was not blinded. The protocol-specified principal endpoints were local-regional tumour relapse, defined as reappearance of cancer at irradiated sites, late normal tissue effects, and quality of life. Analysis was by intention to treat. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN59368779. FINDINGS: 749 women were assigned to the 50 Gy group, 750 to the 41.6 Gy group, and 737 to the 39 Gy group. After a median follow up of 5.1 years (IQR 4.4-6.0) the rate of local-regional tumour relapse at 5 years was 3.6% (95% CI 2.2-5.1) after 50 Gy, 3.5% (95% CI 2.1-4.3) after 41.6 Gy, and 5.2% (95% CI 3.5-6.9) after 39 Gy. The estimated absolute differences in 5-year local-regional relapse rates compared with 50 Gy were 0.2% (95% CI -1.3% to 2.6%) after 41.6 Gy and 0.9% (95% CI -0.8% to 3.7%) after 39 Gy. Photographic and patient self-assessments suggested lower rates of late adverse effects after 39 Gy than with 50 Gy, with an HR for late change in breast appearance (photographic) of 0.69 (95% CI 0.52-0.91, p=0.01). From a planned meta-analysis with the pilot trial, the adjusted estimates of alpha/beta value for tumour control was 4.6 Gy (95% CI 1.1-8.1) and for late change in breast appearance (photographic) was 3.4 Gy (95% CI 2.3-4.5). INTERPRETATION: The data are consistent with the hypothesis that breast cancer and the dose-limiting normal tissues respond similarly to change in radiotherapy fraction size. 41.6 Gy in 13 fractions was similar to the control regimen of 50 Gy in 25 fractions in terms of local-regional tumour control and late normal tissue effects, a result consistent with the result of START Trial B. A lower total dose in a smaller number of fractions could offer similar rates of tumour control and normal tissue damage as the international standard fractionation schedule of 50 Gy in 25 fractions.


Asunto(s)
Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/radioterapia , Fraccionamiento de la Dosis de Radiación , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/patología , Neoplasias de la Mama/cirugía , Intervalos de Confianza , Relación Dosis-Respuesta en la Radiación , Femenino , Estudios de Seguimiento , Humanos , Estimación de Kaplan-Meier , Mastectomía Segmentaria/métodos , Persona de Mediana Edad , Estadificación de Neoplasias , Proyectos Piloto , Modelos de Riesgos Proporcionales , Dosificación Radioterapéutica/normas , Radioterapia Adyuvante , Valores de Referencia , Medición de Riesgo , Factores Sexuales , Análisis de Supervivencia , Resultado del Tratamiento , Reino Unido
10.
Clin Oncol (R Coll Radiol) ; 31(11): 789-796, 2019 11.
Artículo en Inglés | MEDLINE | ID: mdl-31594644

RESUMEN

Merkel cell carcinoma is a rare, aggressive neuroendocrine skin malignancy. Evidence for management comes from case series and single-arm trials. Optimal outcomes require assessment of the patient in a multidisciplinary team setting. Rapid diagnosis and staging are essential for locoregional control and may reduce metastasis. Sentinel lymph node biopsy (SLNB) adds prognostic information. FDG-positron emission tomography has high sensitivity and specificity and affects management in a quarter of cases. Surgical excision and radiotherapy provide good locoregional control even with positive margins. Wide surgical margins are needed if adjuvant radiotherapy is not used. It is uncertain whether adjuvant radiotherapy or elective surgery for uninvolved nodes or for patients selected by positive SLNB improves survival. Total doses of 50 Gy provide high levels of control for microscopic disease but at least 60 Gy should be given for macroscopic disease. Chemotherapy can be given safely with radiotherapy, but the benefit of adjuvant chemotherapy remains uncertain. Trials of adjuvant immune therapy are underway. Unresectable primaries might be controlled with radiotherapy alone or combination systemic therapy, radiotherapy and surgery. Metastatic disease often responds to chemotherapy, but the response duration can be short. Immunity is central to disease control. Immune checkpoint inhibitor treatment resulted in high response rates in chemotherapy-naive patients and lower rates in chemotherapy-refractory patients. Durable responses are observed.


Asunto(s)
Carcinoma de Células de Merkel/tratamiento farmacológico , Carcinoma de Células de Merkel/radioterapia , Neoplasias Cutáneas/tratamiento farmacológico , Neoplasias Cutáneas/radioterapia , Carcinoma de Células de Merkel/patología , Humanos , Pronóstico , Neoplasias Cutáneas/patología
11.
Breast ; 17(1): 98-103, 2008 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-17890090

RESUMEN

BACKGROUND: The aim of this study was to determine whether bone scans (BS) can be avoided if pelvis was included in CT thorax and abdomen to detect bony metastases from breast cancer. MATERIALS AND METHODS: Results of 77 pairs of CT (thorax, abdomen, and pelvis) and BS in newly diagnosed patients with metastatic breast cancer (MBC) were compared prospectively for 12 months. Both scans were blindly assessed by experienced radiologists and discussed at multidisciplinary team meetings regarding the diagnosis of bone metastases. RESULTS: CT detected metastatic bone lesions in 43 (98%) of 44 patients with bone metastases. The remaining patient had a solitary, asymptomatic bony metastasis in shaft of femur. BS was positive in all patients with bone metastases. There were 11 cases of false positive findings on BS. CONCLUSION: Our findings suggest routine BS of patients presenting with MBC is not required if CT (thorax, abdomen, and pelvis) is performed.


Asunto(s)
Neoplasias Óseas/diagnóstico , Neoplasias Óseas/secundario , Neoplasias de la Mama/patología , Radiografía Abdominal/métodos , Radiografía Torácica/métodos , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Persona de Mediana Edad , Estadificación de Neoplasias , Pelvis/diagnóstico por imagen , Estudios Prospectivos , Cintigrafía , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Tomografía Computarizada por Rayos X/métodos
12.
Intern Med J ; 37(8): 523-8, 2007 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-17640187

RESUMEN

BACKGROUND: Australian brown snake (genus Pseudonaja) envenoming causes a venom-induced consumptive coagulopathy (VICC). A proportion of cases go on to develop thrombotic microangiopathy characterized by thrombocytopenia, microangiopathic haemolytic anaemia (MAHA) and acute renal failure (ARF). AIM: The aim of the study was to define better the natural history and empirical treatments for thrombotic microangiopathy in brown snake envenoming. METHODS: A review of brown snake bites recruited to the Australian Snakebite Project (ASP), a national multicentre study of snake envenoming was undertaken. Serial data are recorded on clinical effects and laboratory results, including measurement of venom concentrations. We describe cases of thrombotic microangiopathy and compare these to cases without thrombotic microangiopathy. RESULTS: From 32 cases of brown snake envenoming with severe VICC, four (13%) developed thrombotic microangiopathy, we also included two cases of thrombotic microangiopathy from prior to ASP. All six developed severe thrombocytopenia (<20 x 10(-9)/L), worst 3 days after the bite and resolving over a week, MAHA with fragmented red blood cells on the blood film and five developed anuric ARF requiring dialysis and lasting 2-8 weeks. All six received antivenom, which was delayed compared with other brown snake-envenoming cases. Four were treated with plasmapheresis. The severity and recovery of the thrombocytopenia, anaemia and renal function were similar with and without plasmapheresis. The median length of stay for MAHA cases was 14 days (interquartile range (IQR) 12-14) compared to 1.8 days (IQR 1.3-2) for all other cases. CONCLUSION: Thrombotic microangiopathy resulting from brown snake bite appears to have a good prognosis and management should focus on early antivenom therapy and supportive care including dialysis. The role of plasmapheresis is yet to be defined.


Asunto(s)
Coagulación Intravascular Diseminada/etiología , Elapidae , Mordeduras de Serpientes/complicaciones , Lesión Renal Aguda/etiología , Lesión Renal Aguda/terapia , Adulto , Anciano de 80 o más Años , Anemia Hemolítica/etiología , Anemia Hemolítica/terapia , Animales , Australia , Coagulación Intravascular Diseminada/terapia , Humanos , Masculino , Mordeduras de Serpientes/terapia , Trombocitopenia/etiología , Trombocitopenia/terapia
13.
Clin Pharmacol Ther ; 52(2): 151-9, 1992 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-1505150

RESUMEN

Preclinical studies have established that Sch 37370 (1-acetyl-4-(8-chloro-5,6-dihydro-11H-benzo[5,6]-cyclohepta [1,2-b]pyridin-11-ylidene)piperidine) is an orally active antagonist of platelet-activating factor (PAF) and histamine H1-receptors with potential therapeutic use in the treatment of asthma. To evaluate the efficacy and duration of anti-PAF and antihistamine actions of oral Sch 37370 in humans, a single dose (5 mg/kg) of Sch 37370 was given orally to each of 10 male subjects in a placebo-controlled, double-blind crossover study. Blood samples were drawn before and at various times (2 to 48 hours) after Sch 37370 or placebo. Plasma samples were analyzed for Sch 37370 by a gas chromatographic method, for the anti-PAF activity by measuring the aggregation of platelets stimulated with PAF, and for the antihistamine activity by measuring displacement of [3H]pyrilamine from rat brain membrane binding sites. The plasma anti-PAF activity declined from high levels at 2 hours to barely detectable levels at 24 hours; however, significant activity was still present at 12 hours. The plasma levels of Sch 37370 closely paralleled the anti-PAF profile. The plasma antihistamine activity reached a maximum within 2 to 8 hours and declined thereafter. However, 48 hours after Sch 37370, the antihistamine activity was still present at a significant level in most subjects. It is concluded that, in humans, oral Sch 37370 antagonizes both PAF and histamine with plasma antihistamine activity lasting longer than plasma anti-PAF activity.


Asunto(s)
Antagonistas de los Receptores Histamínicos/farmacocinética , Piperidinas/farmacocinética , Factor de Activación Plaquetaria/antagonistas & inhibidores , Administración Oral , Adulto , Método Doble Ciego , Electrocardiografía/efectos de los fármacos , Antagonistas de los Receptores Histamínicos/sangre , Antagonistas de los Receptores Histamínicos/farmacología , Humanos , Loratadina/análogos & derivados , Masculino , Piperidinas/sangre , Piperidinas/farmacología
14.
FEBS Lett ; 261(2): 247-52, 1990 Feb 26.
Artículo en Inglés | MEDLINE | ID: mdl-1690147

RESUMEN

We have developed two monoclonal antibodies to human lipocortin-1 (103 and 105) as reagents for quantitating the protein in biological systems and neutralizing its activity. Lipo 105 is a high affinity antibody that is functional in ELISA and Western blot formats. The antibody recognizes a site between amino acids 30 and 55 in the lipocortin-1 sequence and can be used on native or denatured protein. Lipo 103 is an antibody that neutralizes the phospholipase A2 inhibitory activity of lipocortin-1 by blocking binding of the protein to phospholipid surfaces. The antibody is specific for native human lipocortin-1. Lipo 103 was recently shown to block lipocortin-1-dependent differentiation of a squamous carcinoma cell line, demonstrating its usefulness as a probe for function.


Asunto(s)
Anticuerpos Monoclonales/inmunología , Proteínas de Unión al Calcio/inmunología , Animales , Anexinas , Anticuerpos Monoclonales/biosíntesis , Especificidad de Anticuerpos , Western Blotting , Proteínas de Unión al Calcio/farmacología , Bromuro de Cianógeno , Ensayo de Inmunoadsorción Enzimática , Epítopos/inmunología , Femenino , Humanos , Indicadores y Reactivos , Ratones , Ratones Endogámicos BALB C , Fragmentos de Péptidos/inmunología , Mapeo Peptídico , Fosfolipasas A/antagonistas & inhibidores , Fosfolipasas A2 , Proteínas Recombinantes
15.
Int J Radiat Oncol Biol Phys ; 23(1): 239-44, 1992.
Artículo en Inglés | MEDLINE | ID: mdl-1572821

RESUMEN

Six-hundred and forty four radiation therapists from 21 European countries, Canada, and the USA responded to a questionnaire regarding the management of three cases of advanced cancer. The cases were a 64-year-old man with brain metastases from small cell carcinoma of the lung; a 64-year-old woman with bone metastases from carcinoma of the breast and a 59-year-old man with squamous cell carcinoma of the bronchus and mediastinal nodes. There was variation as to the perceived prognosis and appropriate aims of therapy, particularly for the case of squamous cell carcinoma of the bronchus. The total dose and number of fractions could be related to the perceived aims and expectations of treatment, for example, those aiming to extend life gave higher doses of radiotherapy and those aiming only to relieve symptoms gave lower. Similarly, those describing treatment as radical and estimating longer survival gave higher doses and more fractions than those treating palliatively. Variations in the role of the radiation oncologist in the management of advanced and metastatic cancer in the USA, Canada and Europe are discussed.


Asunto(s)
Oncología Médica , Metástasis de la Neoplasia , Neoplasias/radioterapia , Actitud del Personal de Salud , Canadá , Europa (Continente) , Humanos , Encuestas y Cuestionarios , Estados Unidos
16.
J Med Chem ; 34(10): 3029-35, 1991 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-1920353

RESUMEN

A specific proteinase of P. falciparum merozoites has been detected by using hydrosoluble fluorogenic peptidic substrates synthesized by classical peptide chemistry; their N-terminal end was acylated by a gluconoyl group that protects them from aminopeptidase degradation and increases their hydrosolubility, and their carboxylic end was substituted by a 3-amino-9-ethylcarbazole group. The sequence Val-Leu-Gly-Lys was found to be the most specific substrate. On this basis, reversible peptidic inhibitors were synthesized by substituting the C-terminal lysyl residue, at the proteolytic site, by different alkylamines and amino alcohols. The activity of these compounds, studied on the P. falciparum proteinase and in in vitro cultures, strongly suggests a specific effect of this peptidic sequence on the reinvasion process. The peptidic inhibitors do not impair the release of merozoites from schizonts, but selectively inhibit the invasion step leading to the formation of rings. Although the natural target of this enzyme is not yet known, these specific peptide inhibitors could lead to a new antimalarial approach.


Asunto(s)
Antimaláricos/farmacología , Eritrocitos/parasitología , Plasmodium falciparum/enzimología , Inhibidores de Proteasas/farmacología , Secuencia de Aminoácidos , Animales , Antimaláricos/síntesis química , Humanos , Datos de Secuencia Molecular , Plasmodium falciparum/efectos de los fármacos , Plasmodium falciparum/fisiología , Inhibidores de Proteasas/síntesis química
17.
Radiother Oncol ; 22(1): 1-6, 1991 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-1947207

RESUMEN

ESTRO members were surveyed by questionnaires regarding the management of three cases of advanced cancer and the organisation of cancer care in their centre. There were 278 replies from within Europe from a total of 21 countries and 231 centres. The cases were a 64-year-old man with brain metastases from a small cell carcinoma of the lung, a 64-year-old woman with bone metastases from carcinoma of the breast on tamoxifen and a 59-year-old man with a squamous cell carcinoma (NSCLC) of the bronchus and positive mediastinal lymph nodes. Over 90% of respondents replied that they would give radiotherapy in each of these cases. The median total doses were 30 Gy for the brain metastases, 30 Gy for the bony metastases and 56 Gy for the case of NSCLC. There was variation as to the perceived prognosis and appropriate aims of therapy, particularly for the case of NSCLC. The total dose and number of fractions of radiotherapy could be related to the perceived aims and expectations of treatment, e.g. those aiming to extend life gave significantly higher total doses of radiotherapy (p = 0.0001) and those aiming to relieve symptoms gave significantly lower total doses (p = 0.0001). Treatment for this case was described as "radical" by 53% of respondents and as "palliative" by 47% and the prognosis was estimated to be less than 12 months by 41% and 1-2 years by 44%. Those describing treatment as radical and estimating longer survival gave higher doses and more fractions than those treating palliatively.(ABSTRACT TRUNCATED AT 250 WORDS)


Asunto(s)
Metástasis de la Neoplasia , Neoplasias/terapia , Europa (Continente)/epidemiología , Humanos , Neoplasias/epidemiología , Neoplasias/patología
18.
Radiother Oncol ; 32(3): 218-25, 1994 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-7529415

RESUMEN

Soft agar clonogenic assays are considered to be a standard method for measuring tumour cell radiosensitivity and it has been widely reported that fibroblast contamination does not occur. We report here that human fibroblasts can proliferate to form colonies in a modified form of the Courtenay-Mills soft agar clonogenic assay. It was observed that early passage skin fibroblasts could form colonies in soft agar, although the plating efficiencies were reduced compared with growth on plastic. It was demonstrated that normal lung could proliferate in agar with similar plating efficiencies to fresh tumours and that fibroblastic cells were present in these cultures. Characterisation of primary lung tumour cultures also showed that fibroblastic cells were present in these cultures. Characterisation of primary lung tumour cultures also showed that fibroblastic cells were present which lacked epithelial features and which resembled closely the cells found in cultures of normal lung. This is an important finding for workers using soft agar assays to culture human tumour cells and is of interest in understanding the processes of normal growth control of human fibroblasts.


Asunto(s)
Medios de Cultivo , Fibroblastos/fisiología , Tolerancia a Radiación , Ensayo de Tumor de Célula Madre/métodos , Agar , División Celular/fisiología , Células Cultivadas , Células Epiteliales , Epitelio/ultraestructura , Fibroblastos/ultraestructura , Humanos , Queratinas , Pulmón/ultraestructura , Neoplasias Pulmonares/ultraestructura , Microscopía Electrónica , Piel/ultraestructura , Células Tumorales Cultivadas
19.
Arch Surg ; 128(2): 138-43; discussion 143-4, 1993 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-8431115

RESUMEN

The body's response to infection/inflammation is initiated by the elaboration of cytokines, such as tumor necrosis factor, interleukin 1-beta (IL-1-beta), IL-6, and IL-8. Cytokines, in turn, stimulate the pituitary-adrenal axis, and it has been suggested that the corticosteroids elaborated serve as negative feedback signals to diminish inflammatory events. To test this hypothesis, we administered hydrocortisone shortly before endotoxin administration to normal volunteers. Steroids greatly reduced the clinical response to endotoxin and attenuated the appearance of tumor necrosis factor, IL-6, and IL-8 in the circulation. In contrast, IL-1-receptor antagonist, a competitive antagonist of the IL-1 receptor, was unaffected by steroid administration. These data suggest that IL-1-receptor antagonist may act in synergism with corticosteroids to reduce inflammation. Elevation of concentrations of these two factors, corticosteroids and IL-1-receptor antagonist, in plasma appears to be the mechanism used by the body to overcome the effects of inflammatory cytokines.


Asunto(s)
Citocinas/sangre , Endotoxinas/efectos adversos , Escherichia coli , Hidrocortisona/uso terapéutico , Lipopolisacáridos/efectos adversos , Receptores de Interleucina-1/antagonistas & inhibidores , Sialoglicoproteínas/sangre , Adulto , Temperatura Corporal/efectos de los fármacos , Fiebre/fisiopatología , Humanos , Hidrocortisona/sangre , Hidrocortisona/farmacología , Proteína Antagonista del Receptor de Interleucina 1 , Interleucina-1/sangre , Interleucina-6/sangre , Interleucina-8/sangre , Masculino , Receptores de Interleucina-1/análisis , Sialoglicoproteínas/fisiología , Factor de Necrosis Tumoral alfa/análisis
20.
J Microbiol Methods ; 46(1): 81-4, 2001 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-11412917

RESUMEN

A method for the infection of non-adherent THP-1 cells and adherent MDBK cells with Cryptosporidium parvum oocysts using isotonic Percoll solutions was developed. Excystation was maximal after 2 h, but toxicity increased with the oocyst/cell ratio and the incubation time. The infection rates did not increase with the oocyst/cell ratio and both cell types were equally parasitized.


Asunto(s)
Cryptosporidium parvum/crecimiento & desarrollo , Povidona , Dióxido de Silicio , Animales , Línea Celular , Células Cultivadas , Cryptosporidium parvum/patogenicidad , Técnicas In Vitro , Óvulo/crecimiento & desarrollo , Recuento de Huevos de Parásitos
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