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1.
Br J Surg ; 107(1): 64-72, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-31609482

RESUMEN

BACKGROUND: The aim was to characterize end-of-life care in patients who have had a leg amputated for peripheral artery disease (PAD) or diabetes. METHODS: This was a population-based retrospective cohort study of patients with PAD or diabetes who died in Ontario, Canada, between 2011 and 2017. Those who had a leg amputation within 3 years of death were compared with a control cohort of deceased patients with PAD or diabetes, but without leg amputation. The patients were identified from linked health records within the single-payer healthcare system. Place and cause of death, as well as health services and costs within 90 days of death, were compared between the amputee and control cohorts. Among amputees, multivariable regression models were used to characterize the association between receipt of home palliative care and in-hospital death, as well as time spent in hospital at the end of life. RESULTS: Compared with 213 300 controls, 3113 amputees were less likely to die at home (15·5 versus 24·9 per cent; P < 0·001) and spent a greater number of their last 90 days of life in hospital (median 19 versus 8 days; P < 0·001). Amputees also had higher end-of-life healthcare costs across all sectors. However, receipt of palliative care was less frequent among amputees than controls (inpatient: 13·4 versus 16·8 per cent, P < 0·001; home: 14·5 versus 23·8 per cent, P < 0·001). Among amputees, receipt of home palliative care was associated with a lower likelihood of in-hospital death (odds ratio 0·49, 95 per cent c.i. 0·40 to 0·60) and fewer days in hospital (rate ratio 0·84, 0·76 to 0·93). CONCLUSION: Palliative care is underused after amputation in patients with PAD or diabetes, and could contribute to reducing in-hospital death and time spent in hospital at the end of life.


ANTECEDENTES: Caracterizar la atención al final de la vida en pacientes con amputación de la extremidad inferior por enfermedad arterial periférica (peripheral arterial disease, PAD) o diabetes. MÉTODOS: Se trata de un estudio de cohortes retrospectivo de base poblacional en sujetos fallecidos con PAD o diabetes en Ontario, Canadá (2011-2017). A partir de los registros sanitarios incluidos en un sistema de salud de una sola entidad pagadora, se identificaron los individuos con amputación de la extremidad inferior en los 3 años previos al fallecimiento y una cohorte control de fallecidos con PAD o diabetes sin amputación. Entre las cohortes de amputados y controles se comparó el lugar del fallecimiento y la causa, así como el uso de servicios sanitarios y costes en los últimos 90 días de vida. En el grupo de los amputados, se utilizaron modelos de regresión para caracterizar la asociación entre recibir cuidados paliativos domiciliarios y el fallecimiento en el hospital, así como los días de estancia hospitalaria al final de la vida. RESULTADOS: En comparación con los controles (n = 213.300), los sujetos con amputación (n = 3.113) era menos probable que fallecieran en el domicilio (16% versus 25%, P < 0,001) y pasaron un mayor número de sus últimos 90 días de vida en el hospital (mediana 19 versus 8 días, P < 0,001). Los costes de atención sanitaria al final de la vida en todos los sectores también fueron mayores para los amputados. Sin embargo, recibir cuidados paliativos fue menos frecuente en los amputados que en los controles (en el hospital 13% versus 17%, P < 0,001; domiciliarios 14% versus 24%, P < 0,001). En el grupo de los amputados, recibir cuidados paliativos domiciliarios se asociaba con una menor probabilidad de fallecimiento en el hospital (razón de oportunidades, odds ratio 0,49, i.c. del 95% 0,40-0,60) y menos días de hospitalización (tasa de riesgo 0,84, i.c. del 95% 0,76-0,93). CONCLUSIÓN: Los cuidados paliativos están infrautilizados en pacientes con PAD o diabetes y pueden contribuir a disminuir los fallecimientos en el hospital y los días de hospitalización al final de la vida.


Asunto(s)
Amputación Quirúrgica/mortalidad , Complicaciones de la Diabetes/mortalidad , Enfermedad Arterial Periférica/mortalidad , Cuidado Terminal/métodos , Anciano , Anciano de 80 o más Años , Amputación Quirúrgica/economía , Causas de Muerte , Complicaciones de la Diabetes/economía , Complicaciones de la Diabetes/cirugía , Femenino , Costos de la Atención en Salud , Servicios de Atención de Salud a Domicilio/economía , Servicios de Atención de Salud a Domicilio/estadística & datos numéricos , Hospitalización/estadística & datos numéricos , Humanos , Masculino , Ontario/epidemiología , Cuidados Paliativos/economía , Cuidados Paliativos/métodos , Cuidados Paliativos/estadística & datos numéricos , Enfermedad Arterial Periférica/economía , Enfermedad Arterial Periférica/terapia , Cuidado Terminal/economía , Cuidado Terminal/estadística & datos numéricos
2.
Transfusion ; 40(3): 290-6, 2000 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-10738028

RESUMEN

BACKGROUND: Careful donor screening and infectious disease marker testing have significantly reduced the incidence of transfusion-transmitted diseases and improved the safety of the blood supply. However, transfusion-transmitted diseases resulting from the use of asymptomatic yet infectious donors continue to put patients at risk. This study was undertaken to determine if third-generation WBC filters could remove Orientia tsutsugamushi-infected cells from contaminated blood. STUDY DESIGN AND METHODS: Packed RBCs were inoculated with human MNCs infected with O. tsutsugamushi at levels estimated to occur in asymptomatic infectious donors. WBC reduction was accomplished with a third-generation WBC filter. Prefiltration and postfiltration specimens were collected, serially diluted, and injected into mice to determine the infectivity of the samples. RESULTS: Mice receiving WBC-reduced packed RBCs showed no signs of illness or markers of infectivity, which suggested that a reduction of as much as 10(5) infectious rickettsiae could be achieved by filtration. CONCLUSION: The high-efficiency, third-generation, WBC-reduction filters that were tested may provide protection against the transfusion transmission of scrub typhus rickettsiae by removing from contaminated blood cells that contain intracellular bacteria.


Asunto(s)
Hemofiltración , Leucocitos/citología , Monocitos/microbiología , Orientia tsutsugamushi , Infecciones por Rickettsia/transmisión , Reacción a la Transfusión , Animales , ADN Bacteriano/sangre , Modelos Animales de Enfermedad , Humanos , Ratones , Orientia tsutsugamushi/genética , Reacción en Cadena de la Polimerasa/métodos , Tifus por Ácaros/sangre
3.
Steroids ; 64(8): 499-509, 1999 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-10493594

RESUMEN

Ceramide is known to have major roles in the control of cell proliferation, differentiation, and apoptosis. Recent studies also have shown that ceramide affects steroid production by JEG-3 choriocarcinoma cells, acutely dispersed rat Leydig cells, and ovarian granulosa cells, but the mechanism by which this occurs is unknown. Because ceramide induces apoptosis in many different cell types, we hypothesized that ceramide might affect steroidogenesis and/or induce apoptosis in MA-10 murine Leydig cells. To test this, MA-10 cells were incubated with either the water soluble C2-ceramide, (N-acetyl-sphingosine, 0.01-10 cm); bacterial sphingomyelinase (1-100 mU/ml); or C2-dihydroceramide (N-acetyl-sphinganine, 0.1-10 microM). The data show that N-acetyl-sphingosine significantly increased basal (0.87 +/- 0.2 vs. 0.42 +/- 0.09 ng/mg cell protein, P < 0.01) and human chorionic gonadotropin (hCG) stimulated progesterone (P) synthesis (204 +/- 12 vs. 120 +/- 5 ng/mg cell protein, P < 0.001); as did sphingomyelinase (basal P = 0.83 +/- 0.1 ng/mg cell protein, P < 0.01; hCG stimulated P = 173 +/- 7 ng/mg cell protein, P < 0.001). C2-dihydroceramide also increased basal P synthesis but was less effective than ceramide on a molar basis. Neither sphingomyelinase (100 mU/ml) nor ceramide (10 microM) had any effect on cAMP production or human chorionic gonadotropin binding; and neither induced any signs of apoptosis (FragEL DNA fragmentation assay and electron microscopy). Cells incubated with anti-Fas (300 ng/ml) demonstrated DNA fragmentation, nuclear condensation, and frequent apoptotic bodies, but had no change in P synthesis. These data show that ceramide significantly increases MA-10 Leydig cell P synthesis but does not induce apoptosis. The mechanism by which ceramide increases steroid hormone synthesis remains unknown but does not appear to be linked to the induction of apoptosis in MA-10 cells.


Asunto(s)
Ceramidas/fisiología , Células Intersticiales del Testículo/metabolismo , Progesterona/biosíntesis , Animales , Apoptosis/efectos de los fármacos , Apoptosis/fisiología , Células Cultivadas , Ceramidas/metabolismo , Ceramidas/farmacología , Gonadotropina Coriónica/metabolismo , Gonadotropina Coriónica/farmacología , Cromatografía Líquida de Alta Presión , AMP Cíclico/metabolismo , Fragmentación del ADN , Relación Dosis-Respuesta a Droga , Células Intersticiales del Testículo/efectos de los fármacos , Células Intersticiales del Testículo/ultraestructura , Masculino , Ratones , Esfingomielina Fosfodiesterasa/farmacología , Receptor fas/inmunología
4.
Am J Gastroenterol ; 94(3): 744-50, 1999 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-10086661

RESUMEN

OBJECTIVE: The aim of this study was to determine whether lectin binding to exfoliated human colonocytes could be used as a noninvasive test for colorectal polyps or cancer. METHODS: Colonocytes were harvested from 31 patients (10 controls, 10 with adenomatous polyps, and 11 with cancer), incubated with a panel of fluorescent-labeled lectins, and assayed by flow cytometry. RESULTS: The lectins jacalin (JAC) and wheat germ agglutinin (WGA) were useful in predicting the presence of a colorectal neoplasm (p = 0.0018 for JAC and p = 0.0099 for WGA). For JAC, sensitivity reached 81% with a specificity of 80%, and for WGA the sensitivity and specificity were both 75%. CONCLUSIONS: Lectin binding to human colonocytes can predict the presence of malignant and premalignant lesions of the colon, and has potential as a noninvasive screening tool for colorectal neoplasms.


Asunto(s)
Colon/metabolismo , Neoplasias Colorrectales/diagnóstico , Lectinas/metabolismo , Lectinas de Plantas , Pólipos Adenomatosos/diagnóstico , Pólipos Adenomatosos/metabolismo , Colon/citología , Pólipos del Colon/diagnóstico , Pólipos del Colon/metabolismo , Neoplasias Colorrectales/metabolismo , Heces/citología , Citometría de Flujo , Humanos , Proyectos Piloto , Sensibilidad y Especificidad , Aglutininas del Germen de Trigo/metabolismo
5.
Transfusion ; 38(7): 680-9, 1998 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-9683108

RESUMEN

BACKGROUND: The purpose of this study was to determine whether infective Orientia tsutsugamushi, the etiologic agent of scrub typhus, could survive normal blood banking processing and storage procedures. STUDY DESIGN AND METHODS: Mononuclear cells isolated from whole blood by density gradient centrifugation were inoculated with O. tsutsugamushi, Karp strain. Infection of the mononuclear cells was confirmed by Giemsa stain, direct fluorescent antibody assay, and polymerase chain reaction using primers specific for the groESL operon of O. tsutsugamushi. The quantity of rickettsial particles in each preparation was determined by direct counts from the Giemsa-stained preparations. Infected mononuclear cells were returned to their respective aliquots of packed red blood cells, which were then either stored at 4 degrees C or glycerolized and frozen at -70 degrees C. RESULTS: Rickettsiae survived up to 10 days (but not 30 days) of refrigerated storage and 45 days of frozen storage, as determined by inoculation of mice with 0.5-mL aliquots of the blood components. Infection of the mice was determined by illness, death, direct fluorescent antibody assay of peritoneal smears, polymerase chain reaction of blood, and enzyme-linked immunosorbent assay detection of antibodies in plasma. CONCLUSION: Because the quantity of rickettsiae injected into the mice was comparable to the quantity reported in the literature for human blood during natural infections, scrub typhus could present a risk in blood collected from donors in endemic areas. This may especially be true, because people can be rickettsemic before illness, after successful antibiotic treatment, and chronically after resolution of disease.


Asunto(s)
Transfusión de Eritrocitos/efectos adversos , Eritrocitos/microbiología , Orientia tsutsugamushi/aislamiento & purificación , Tifus por Ácaros/transmisión , Animales , Bancos de Sangre/normas , Humanos , Ratones , Orientia tsutsugamushi/fisiología
6.
Ann Clin Lab Sci ; 26(3): 234-42, 1996.
Artículo en Inglés | MEDLINE | ID: mdl-8726216

RESUMEN

Activation of the immune system has profound effects on endocrine function which are mediated by cytokines including tumor necrosis factor-alpha (TNF alpha). In vitro, TNF alpha has been shown to directly inhibit Leydig cell testosterone (T) production, but the mechanism of this effect is still unclear. Recent studies using cultured human fibroblasts have shown that TNF alpha stimulates the activity of neutral sphingomyelinase (SMase) which hydrolyses sphingomyelin (SM) generating ceramide and changing membrane components including cholesterol. The cellular affects of increased SMase activity have been reproduced in vitro by the addition of exogenous SMase. In cultured fibroblasts, exogenous SMase decreases cholesterol synthesis. These findings led us to hypothesize that SMase might be important in the regulation of steroid hormone synthesis. To our knowledge, no previous studies have investigated this possibility. To test this hypothesis, rat Leydig cell enriched cultures were incubated in media containing SMase (0.1 to 100 mU/ml) or in control media. SMase significantly decreased basal and human chorionic gonadotropin (hCG) stimulated T production. SMase also decreased hCG binding and hCG stimulated adenosine 3':5'-cyclic monophosphate (cAMP). N-acetyl-sphingosine (0.1 to 10 microM), a water soluble ceramide, was used to determine whether or not the effects of SMase could be reproduced by ceramide addition. N-acetyl-sphingosine had only slight effects on basal T and cAMP, and no effect on hCG binding or hCG stimulated T or cAMP. These data suggest the metabolism of membrane sphingomyelin may be an important regulatory pathway in the control of Leydig cell function.


Asunto(s)
Células Intersticiales del Testículo/metabolismo , Esfingomielina Fosfodiesterasa/farmacología , Animales , Bucladesina/farmacología , Supervivencia Celular/efectos de los fármacos , Gonadotropina Coriónica/metabolismo , Gonadotropina Coriónica/farmacología , AMP Cíclico/metabolismo , Células Intersticiales del Testículo/efectos de los fármacos , Masculino , Ratas , Ratas Sprague-Dawley , Receptores de HL/metabolismo , Esfingomielina Fosfodiesterasa/metabolismo , Esfingosina/análogos & derivados , Esfingosina/farmacología , Testosterona/biosíntesis
7.
Transfusion ; 36(4): 318-21, 1996 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-8623131

RESUMEN

BACKGROUND: Reticulocytes are important in the phenotyping of transfused patients. Reticulocytes can persist in blood units for the shelf life of the unit. STUDY DESIGN AND METHODS: Temperature dependence of reticulocyte persistence was examined in vitro at 4, 24, and 37 degrees C by using thiazole orange staining and flow cytometric analysis. Two-color flow cytometric analysis was used to evaluate the persistence of donor reticulocytes in transfused patients. RESULTS: Flow cytometric analysis using thiazole orange demonstrated that persistence of reticulocytes in units of stored CPDA-1 blood was temperature-dependent. Reticulocytes disappeared over 13 and 6 days at 24 degrees C and 37 degrees C, respectively, but at 4 degrees C the reticulocyte count changed little over 35 days. Two-color flow cytometric analysis of reticulocyte antigens was used to follow donor reticulocytes in 14 transfusion events in nine different patients. Donor reticulocytes persisted through 24 hours in 75 percent of the patients and were detectable at 48 hours in three patients. CONCLUSION: This study demonstrates that reticulocytes persist during refrigerated storage; they are detectable in the circulation of most recipients for the first 24 hours after transfusion and in the circulation of a few recipients after 48 hours. These findings may have relevance for separation techniques based on reticulocyte density in samples drawn shortly after transfusion and for evaluation of reticulocyte counts in patients with hematologic abnormalities.


Asunto(s)
Donantes de Sangre , Conservación de la Sangre , Transfusión de Eritrocitos , Reticulocitos/trasplante , Diferenciación Celular , Supervivencia Celular , Recuento de Eritrocitos , Citometría de Flujo , Humanos , Reticulocitos/citología
8.
Clin Exp Rheumatol ; 14(1): 95-8, 1996.
Artículo en Inglés | MEDLINE | ID: mdl-8697667

RESUMEN

Leukocyte adhesion deficiency (LAD) is a rare inherited immunodeficiency that is characterized by deficiency of the beta 2 integrin leukocyte adhesion molecules Mac-1, LFA-1, and p150,95. We describe a case of the severe form of LAD in an infant with recurrent infections and with a complete deficiency of beta 2 integrin molecules, and review the clinical aspects of the syndrome.


Asunto(s)
Síndrome de Deficiencia de Adhesión del Leucocito , Antígenos CD18/metabolismo , Moléculas de Adhesión Celular/metabolismo , Femenino , Humanos , Lactante , Síndrome de Deficiencia de Adhesión del Leucocito/genética , Síndrome de Deficiencia de Adhesión del Leucocito/inmunología , Síndrome de Deficiencia de Adhesión del Leucocito/metabolismo , Linaje
9.
Am J Trop Med Hyg ; 53(6): 602-6, 1995 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-8561261

RESUMEN

Recent unpublished reports from northern Thailand of severe and sometimes fatal cases of scrub typhus, despite appropriate antibiotic therapy, suggest that resistance may occur. Current antibiotic susceptibility methods that use direct microscopic counts of Giemsa-stained cells or mouse protection assays are slow, labor-intensive, and expensive. We explored the use of flow cytometry to measure rickettsial infection in vitro in L-929 cells treated with and without doxycycline, ciprofloxacin, erythromycin, and chloramphenicol. It was possible to detect the rickettsiae down to a level of 83% of the cells infected, mean of 37 rickettsiae per cell, and 40% of cells with too many rickettsiae to count. This level of sensitivity was sufficient to determine the inhibitory effect of all four drugs at standard screening concentrations. At lower concentrations of doxycycline, flow cytometry detected inhibition of rickettsial growth at a concentration of 6.25 x 10(-2) micrograms/ml but not at 6.25 x 10(-3) micrograms/ml, suggesting that the minimum inhibitory concentration is somewhere between these two values. The data from this study show that flow cytometry permits the rapid screening of numerous rickettsial isolates for their susceptibility to a variety of antibiotics, but that visual counts of infected cells provide a more precise indication of rickettsial growth.


Asunto(s)
Antibacterianos/farmacología , Citometría de Flujo/métodos , Orientia tsutsugamushi/crecimiento & desarrollo , Animales , Anticuerpos Antibacterianos/inmunología , Recuento de Células , Línea Celular , Células Cultivadas , Cloranfenicol/farmacología , Ciprofloxacina/farmacología , Doxiciclina/farmacología , Eritromicina/farmacología , Fibroblastos/microbiología , Fluoresceína-5-Isotiocianato , Ratones , Pruebas de Sensibilidad Microbiana , Orientia tsutsugamushi/efectos de los fármacos , Orientia tsutsugamushi/inmunología
10.
Antimicrob Agents Chemother ; 39(11): 2406-10, 1995 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-8585717

RESUMEN

In an effort to find a potential alternative treatment for scrub typhus, we evaluated the effectiveness of the standard drug doxycycline and the new macrolide azithromycin against a doxycycline-susceptible strain (Karp) and a doxycycline-resistant strain (AFSC-4) of Rickettsia tsutsugamushi. The antibiotics were tested in an in vitro assay system in which infected mouse fibroblast cells (L929) were incubated for 3 days in various concentrations of the drugs. Rickettsial growth was evaluated by direct visual counts of rickettsiae in Giemsastained cells or by flow cytometry. Initial tests were conducted at the concentration of each antibiotic considered to be the upper breakpoint for susceptibility (16 micrograms/ml for doxycycline and 8 micrograms/ml for azithromycin). Growth of both Karp and AFSC-4 was strongly inhibited with both antibiotics, as measured by visual counts, although the percentage of cells infected with AFSC-4 in the presence of doxycycline was three times greater than the percentage of cells infected with Karp but was only 60% as great as the percentage of cells infected with Karp in the presence of azithromycin. Flow cytometry confirmed that rickettsial growth occurred in the absence of antibiotics, but it failed to detect it in the presence of high concentrations of either drug. Visual counts of rickettsial growth at lower concentrations of the antibiotics (0.25 to 0.0078 microgram/ml) showed that the Karp strain was 16 times more susceptible that the AFSC-4 strain to doxycycline. Azithromycin was much more effective than doxycycline against AFSC-4, inhibiting rickettsial growth at 0.0156 microgram/ml to levels below that achieved by 0.25 microgram of doxycycline per ml. Azithromycin was also more effective than doxycycline against the Karp strain, causing greater reductions in the number of rickettsiae per cell at lower concentrations. If in vivo testing confirms the in vitro effectiveness of azithromycin, it may prove to be the drug of choice for the treatment of scrub typhus in children and pregnant women, who should not take doxycycline, and in patients with refractory disease from locations where doxycycline-resistant strains of R. tsutsugamushi have been found. When tested in an in vitro assay system, azithromycin was more effective than doxycycline against doxycycline-susceptible and -resistant strains of R. tsutsugamushi.


Asunto(s)
Antibacterianos/farmacología , Azitromicina/farmacología , Doxiciclina/farmacología , Orientia tsutsugamushi/efectos de los fármacos , Tifus por Ácaros/microbiología , Animales , Fibroblastos , Citometría de Flujo , Células L , Ratones , Pruebas de Sensibilidad Microbiana , Orientia tsutsugamushi/crecimiento & desarrollo , Tifus por Ácaros/tratamiento farmacológico , Resistencia a la Tetraciclina
11.
Ann Allergy Asthma Immunol ; 75(4): 348-50, 1995 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-7583852

RESUMEN

BACKGROUND: Birds have been associated with many diseases including hypersensitivity pneumonitis and allergic diseases such as asthma and rhinitis. Bird antigen from homes of patients with hypersensitivity pneumonitis persists long after the bird is removed from the home. This may account for the persistence of symptoms, signs, and bird-specific IgG in patients with hypersensitivity pneumonitis. Tannic acid application has been effective in decreasing cat and mite allergen levels. No data have been available on tannic acid's effect on bird antigen. OBJECTIVE: It is the purpose of this study to determine whether tannic acid reduces bird antigen in the home. METHOD: Dust samples were collected from homes with bird antigen before and after application of tannic acid. Samples were assayed for bird antigen levels using a competitive inhibition ELISA. Pre- and post-bird antigen levels were compared using a paired t test to determine whether antigen was reduced significantly. RESULTS: There was not a statistical difference between bird antigen levels before and after application of tannic acid as compared by paired t test (P = .09). CONCLUSION: Tannic acid is not effective in decreasing bird antigen levels. In patients with hypersensitivity pneumonitis or allergic disease to birds, the bird should be removed from the home and environmental cleanup should be undertaken, but tannic acid application is not indicated.


Asunto(s)
Alérgenos/efectos de los fármacos , Alveolitis Alérgica Extrínseca/inmunología , Antígenos/efectos de los fármacos , Aves/inmunología , Taninos Hidrolizables/farmacología , Alveolitis Alérgica Extrínseca/etiología , Animales , Antígenos/uso terapéutico , Contaminación Ambiental/efectos adversos , Humanos , Taninos Hidrolizables/uso terapéutico
12.
Clin Immunol Immunopathol ; 76(2): 209-13, 1995 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-7614740

RESUMEN

We have studied the influence of triiodothyronine (T3), thyroxine (T4), thyrotropin (TSH), and methimazole (MMI) on the expression of major histocompatibility (MHC) Class II antigen expression in human thyroid cells. T3, T4, TSH, and MMI in various combinations were added together with interferon-gamma (IFN-gamma) to human thyrocytes or to cultured FRTL-5 cells. Neither T3 nor T4, alone, caused inhibition of the IFN-gamma stimulation of thyrocyte HLA-DR expression. Moreover, the combination of both drugs at various concentrations did not inhibit this expression except only in low ranges (T3 at 0.3 nmol/liter and T4 at 12.9 nmol/liter). MMI only at a concentration of 3.0 mmol/liter caused significant inhibition of IFN-gamma-induced HLA-DR expression. However, the addition of T3 (range, 0.3-9.2 nmol/liter) or T4 (12.9-129.0 nmol/liter) prevented the MMI-induced inhibition. This phenomenon may be explained by the action of MMI on inhibiting the synthesis of T3 and T4. At a concentration of 100 microU/ml, TSH enhanced IFN-gamma-induced HLA-DR expression. It is possible that TSH induced the expression of large numbers of IFN-gamma receptors, thereby enhancing the production of HLA-DR in response to IFN-gamma. Our studies suggest that MMI does not alter thyrocyte HLA-DR expression in vitro, especially when combined with T3 or T4; however, MMI may still induce or perpetuate immune effects in vivo secondary to its influence on thyroid hormone production or thyroid antigen presentation.


Asunto(s)
Antígenos de Histocompatibilidad Clase II/biosíntesis , Metimazol/farmacología , Glándula Tiroides/efectos de los fármacos , Glándula Tiroides/metabolismo , Hormonas Tiroideas/fisiología , Animales , Línea Celular , Antígenos HLA-DR/biosíntesis , Humanos , Interferón gamma/fisiología , Ratas , Tirotropina/fisiología , Tiroxina/fisiología , Triyodotironina/fisiología
13.
Clin Immunol Immunopathol ; 75(2): 117-24, 1995 May.
Artículo en Inglés | MEDLINE | ID: mdl-7535671

RESUMEN

The human TSH receptor represents the primary target of thyroid-stimulating immunoglobulins responsible for the hyperthyroidism of Graves' disease. In the present series of investigations, the distribution of T cell epitopes has been mapped using synthetic peptides spanning the entire extracellular region of the human TSH receptor. In vitro proliferative responses of the mononuclear cells were measured using flow cytometric analysis of bromodeoxyuridine incorporation into nuclei. In 8 of 11 samples from patients with Graves' disease, at least one (and up to 9) regions of the human TSH receptor induced proliferation, with the mean stimulation index being 39.8 +/- 47.3. No single universal stimulatory peptide was identified. In contrast, stimulation was not observed in three control subjects, while one control subject showed minimal stimulation (index of 5.7) to peptides encompassing a limited area (amino acids 31-65). The immunodominant epitope of patients with recent-onset Graves' disease was localized between amino acids 271 and 365, whereas the immunodominant epitope of patients with disease duration greater than 1 year localized between amino acids 91 and 215. We conclude that the bromodeoxyuridine incorporation method is a useful and important tool for detecting antigen-induced lymphocyte proliferation. The TSH receptor-specific T cells from different Graves' disease patients recognize variable distinct sites within the extracellular region of the TSH receptor, and the immunodominant epitope apparently shifts toward the N-terminus of the receptor protein during the course of treated Graves' disease.


Asunto(s)
Receptores de Tirotropina/inmunología , Linfocitos T/inmunología , Tiroiditis Autoinmune/inmunología , Bromodesoxiuridina/farmacocinética , Reacciones Cruzadas/genética , Epítopos , Citometría de Flujo , Genes nef , Enfermedad de Graves/inmunología , Humanos , Leucocitos Mononucleares/metabolismo , Péptidos/análisis , Receptores de Tirotropina/análisis , Receptores de Tirotropina/química , Linfocitos T/química , Linfocitos T/ultraestructura , Linfocitos T Colaboradores-Inductores/química , Linfocitos T Colaboradores-Inductores/ultraestructura
14.
Ann Allergy Asthma Immunol ; 74(1): 39-44, 1995 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-7719881

RESUMEN

BACKGROUND: Adverse reactions to mosquito bites have been recognized for some time. These usually consist of large local swellings and redness, generalized urticaria, angioedema and less easily definable responses such as nausea, dizziness, headaches, and lethargy. METHODS: We report two patients who experienced systemic anaphylaxis from mosquito bites. Both were skin tested and given immunotherapy using whole body mosquito extracts. RESULTS: Skin testing using whole body mosquito extracts was positive to Aedes aegypti at 1/1,000 weight/volume (wt/vol) in one patient and to Aedes aegypti at 1/100,000 wt/vol, and Culex pipiens at 1/10,000 wt/vol in the other. Skin testing of ten volunteers without a history of adverse reactions to mosquito bites was negative. Immunotherapy using these extracts resulted in resolution of adverse reactions to mosquito bites in one patient and a decrease in reactions in the other. CONCLUSIONS: Immunotherapy with whole body mosquito extracts is a viable treatment option that can play a role in patients with mosquito bite-induced anaphylaxis. It may also result in severe side effects and one must determine the benefit versus risks for each individual patient.


Asunto(s)
Anafilaxia/etiología , Anafilaxia/terapia , Culicidae , Inmunoterapia , Mordeduras y Picaduras de Insectos/complicaciones , Adulto , Animales , Culicidae/inmunología , Humanos , Masculino , Pruebas Cutáneas , Extractos de Tejidos/inmunología
15.
J Allergy Clin Immunol ; 94(1): 27-32, 1994 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-8027495

RESUMEN

BACKGROUND: We compared the effects of an acaricide, benzyl benzoate, with the effects of baking soda control applied to bedroom and living room carpets on house dust mite allergen levels, lung function, and medication use in 12 adult patients with asthma for 12 months. METHODS: This was a randomized, double-blind, placebo-controlled study. Patients were enrolled from the allergy clinic of a large tertiary care center in a metropolitan area. All patients had positive dust mite puncture test results. Six patients used benzyl benzoate, and six used baking soda. Other aggressive mite control measures were implemented uniformly in each group. Subjects were to make two carpet applications, at baseline and at 6 months according to the manufacturer's recommendations. Dust samples were collected in bedroom and living room carpets at 0, 3, 6, 9, and 12 months; and quantities of Der p I and Der f I allergens were determined. Spirometry was done every 3 months, and peak flow rates were recorded for 10 days after each dust sampling. RESULTS: There were no significant differences in mean allergen levels between the two groups over time at either site. There were no significant changes in lung function or medication use for either group. CONCLUSIONS: Benzyl benzoate powder applications may not be effective when done according to manufacturer's instructions. Further studies are necessary to test effectiveness when applied more frequently and for longer periods.


Asunto(s)
Alérgenos/efectos de los fármacos , Benzoatos/farmacología , Insecticidas/farmacología , Ácaros/inmunología , Adulto , Anciano , Alérgenos/análisis , Animales , Asma/tratamiento farmacológico , Asma/epidemiología , Asma/fisiopatología , Distribución de Chi-Cuadrado , Método Doble Ciego , Polvo/análisis , Femenino , Pisos y Cubiertas de Piso , Humanos , Masculino , Persona de Mediana Edad , Hipersensibilidad Respiratoria/tratamiento farmacológico , Hipersensibilidad Respiratoria/epidemiología , Hipersensibilidad Respiratoria/fisiopatología , Bicarbonato de Sodio/farmacología
17.
Transfusion ; 34(3): 233-7, 1994 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-8146896

RESUMEN

BACKGROUND: Reticulocyte phenotyping is used for transfused patients, who have red cell antibodies, to match blood for subsequent transfusion. Current methods are labor-intensive and require a significant amount of sample. STUDY DESIGN AND METHODS: A simple dual-color flow cytometry method developed for antigen typing of reticulocytes in mixed red cell populations is reported. Antigens were labeled by an indirect immunofluorescence technique using undiluted reagent sera as the primary label, biotinylated goat anti-human IgG as the secondary label, and avidin-phycoerythrin as the fluorescent stain. Reticulocytes were labeled with a thiazole orange fluorescent stain. Reticulocyte identification and antigen typing were performed on 319 samples to establish the validity of the procedure. Mixed red cells were prepared in all possible c antigen combinations to simulate transfusion concentrations of 25, 50, and 75 percent. RESULTS: The anti-c flow cytometry profiles readily distinguished between antigen-positive and antigen-negative populations and allowed the detection of reticulocytes at all simulated transfusion concentrations. Similar results were obtained in experiments using C, K, s, Fya, Fyb, Jka, or Jkb sera against equal volumes of antigen-positive and -negative cells. Anti-S gave inconsistent results. The in vitro results were confirmed in 19 transfused patients who had received red cells antigenically different from their own as well as cells from 1 chimera blood donor. CONCLUSION: This method provides a simpler, safer, less labor-intensive, and less subjective technique requiring far less sample volume than current methods for antigen typing of reticulocytes in mixed red cell samples from recently transfused patients.


Asunto(s)
Transfusión Sanguínea , Eritrocitos/inmunología , Citometría de Flujo/métodos , Inmunofenotipificación , Antígenos de Superficie/sangre , Antígenos de Grupos Sanguíneos/inmunología , Técnica del Anticuerpo Fluorescente , Humanos , Reticulocitos/inmunología
18.
Ann Allergy ; 69(6): 510-2, 1992 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-1471783

RESUMEN

Hypersensitivity pneumonitis (HP) secondary to bird exposure is treated with glucocorticosteroids and avoidance. Despite therapy, symptoms may persist for a prolonged time. Just as cat antigen, Fel d 1, may persist for greater than 20 weeks after cat removal, there may be persistent bird antigen to explain prolonged symptoms in bird HP. It was the intent of this study to determine household distribution and persistence of bird antigen after removal of the bird from the patient's home. The homes of patients with birds were followed serially after bird removal with multiple samples collected using a hand-held vacuum cleaner. Bird antigen levels were determined by an inhibition enzyme-linked immunoassay. In five homes the antigen declined gradually despite extensive environmental control measures, with high levels still detectable at 18 months in one home. This data suggests that high levels of bird antigen can be detected for prolonged periods of time after bird removal and environmental cleanup. The antigen may account for the persistence of disease in some patients with HP. In severe HP, the preferred therapy may be temporary relocation of the patient away from the room in which the bird was housed, in addition to corticosteroids, until the patient's environment is demonstrated to be relatively bird antigen-free.


Asunto(s)
Contaminación del Aire/análisis , Antígenos/análisis , Aves/inmunología , Alveolitis Alérgica Extrínseca/sangre , Alveolitis Alérgica Extrínseca/inmunología , Animales , Antígenos/sangre , Humanos , Factores de Tiempo
19.
J Allergy Clin Immunol ; 89(4): 836-43, 1992 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-1560167

RESUMEN

The effects of supplementary computer instruction in house dust mite-avoidance measures on adherence to implementing measures, on home dust mite-allergen levels, and on symptomatology were investigated in 52 adult patients with mite-associated asthma. Twenty-six patients received conventional instruction (counseling and written instruction) and the other 26 patients received conventional plus 22 minutes of interactive computer-assisted instruction. Instructions were aimed at mite-avoidance measures. Pre- and postinstruction dust samples were collected, and adherence was monitored. All patients kept symptom diaries twice a day. Patients' progress was followed for 12 weeks, and all patients completed the study. Adherence, number of observed and self-reported mite-avoidance measures implemented after visit, was higher for the computer group (p = 0.023). The computer-instructed group achieved significantly lower levels of mite allergen in bedroom carpets (p = 0.004) with mean levels of mite allergen declining from 6.5 +/- 7.6 to 2.2 +/- 4.3 micrograms/gm of dust (two-site monoclonal antibody assays), whereas levels for the conventional-instructed group did not change. Moreover, by study weeks 9 and 10, the computer-instructed group was significantly less symptomatic (p = 0.033). Mean symptom scores for this group decreased from 12.4 to 7.7, compared with 16.4 to 14.3. Conventional instruction supplemented with computer instruction is suggested in mite education.


Asunto(s)
Alérgenos/inmunología , Asma/inmunología , Educación en Salud , Hipersensibilidad/inmunología , Ácaros/inmunología , Educación del Paciente como Asunto , Adolescente , Adulto , Anciano , Contaminación del Aire/análisis , Alérgenos/análisis , Animales , Instrucción por Computador , Consejo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Educación del Paciente como Asunto/métodos
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