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1.
J Thromb Haemost ; 3(11): 2449-56, 2005 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-16241943

RESUMEN

OBJECTIVE: A clinical diagnosis of pulmonary embolism (PE) is confirmed objectively in 20-30% of patients. Helical computed tomography (CT) can allow an alternative diagnosis to be made. The frequency and validity of alternative diagnoses on helical CT in consecutive patients presenting with clinically suspected PE was assessed. PATIENTS AND METHODS: In all 512 prospectively analyzed patients helical CT scan was performed, and apart from presence or absence of PE, pathologic changes in lung parenchyma, mediastinum, cardiovascular system, pleura and skeleton were recorded. When possible an alternative diagnosis was given and compared with the final diagnosis after 3 months follow-up. RESULTS: In 130 patients (25.4%) PE was excluded and an alternative diagnosis considered likely. In 123 of the 130 patients (94.6%) this diagnosis was unchanged at 3 months follow-up. The diagnoses included pneumonia (n = 67), malignancy (n = 22), pleural fluid (n = 10), cardiac failure (n = 10), COPD (n = 6) and a variety of other causes (n = 15). The diagnosis changed at follow-up in seven patients (5.4%). An initial diagnosis of pneumonia changed to malignancy in two patients and to pleuritis and cardiac failure in one patient each. In two other patients malignancy and chronic obstructive pulmonary disease (COPD) were ruled out and the diagnosis changed to pneumonia. In one patient the final diagnosis remained unknown after an initial suspicion of malignancy. CONCLUSION: In clinically suspected PE helical CT allows a reliable alternative diagnosis to be made in 25.4% of patients. This feature is an unique advantage in comparison with other diagnostic tests and supports the decision of taking helical CT as first line test in suspected PE.


Asunto(s)
Embolia Pulmonar/diagnóstico por imagen , Tomografía Computarizada Espiral , Algoritmos , Diagnóstico Diferencial , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Neoplasias/diagnóstico por imagen , Evaluación de Resultado en la Atención de Salud , Derrame Pleural/diagnóstico por imagen , Neumonía/diagnóstico por imagen , Estudios Prospectivos
2.
Ned Tijdschr Geneeskd ; 149(11): 568-76, 2005 Mar 12.
Artículo en Holandés | MEDLINE | ID: mdl-15799639

RESUMEN

The Dutch national guidelines for the diagnosis of patients with clinically suspected pulmonary embolism (from 1992 en 1998) are poorly followed in clinical practice, due especially to practical objections. A large multicentre trial to investigate the diagnostic accuracy of the available modalities and of recently developed techniques such as D-dimer determination, (99m)Tc-gas-scintigraphy and spiral CT scanning was started in I997. In the first phase, the diagnostic value was assessed of: spiral CT (sensitivity 69%, specificity 84%; sensitivity for segmental and larger pulmonary embolisms (PE) 86% and for subsegmental PE 21%), (99m)Tc-gas-ventilation scintigraphy (no improvement compared to conventional ventilation scintigraphy), D-dimer determination (sensitivity for segmental PE 93% and for subsegmental PE 53%, specificity 63%), clinical decision rules (in combination with D-dimer determination; sensitivity 100%, specificity 11%) and echography of the deep venous system (sensitivity 26% for segmental PE and 7% for subsegmental PE, specificity 97%). In the second phase, the feasibility of two new potentially cost-effective diagnostic algorithms was evaluated on the basis of the results obtained in the first phase and data in the literature. In 631 patients, a clinical risk estimate was made and D-dimer determination was done, followed by a ventilation-perfusion scan and serial compression echography of the leg veins. An apparent recurrence of PE occurred in 6 of 466 patients in whom no PE had been found originally (1.3%; 95% CI: 0.5-2.8). The average costs were 812 Euro,--per patient. In 510 patients, a spiral CT followed by compression echography was performed. Recurrent PE occurred in 3 of 378 patients with initial normal tests (0.8%; 95% CI: 0.2-2.3). The average costs were 883 Euro,--per patient. A combination of both strategies can be cost-effective with a cost 674 Euro,--per patient (recurrence rate: 1.9%). Both the strategy starting with a clinical-risk estimate and a D-dimer determination as well as the strategy consisting of spiral CT and serial echography were safe and cost-effective. According to the results of a survey of hospital directors, internists and pulmonologists, both are well accepted in clinical practice.


Asunto(s)
Algoritmos , Embolia Pulmonar/diagnóstico , Cintigrafía/métodos , Tomografía Computarizada Espiral/métodos , Medios de Contraste , Análisis Costo-Beneficio , Humanos , Estudios Multicéntricos como Asunto , Valor Predictivo de las Pruebas , Embolia Pulmonar/diagnóstico por imagen , Cintigrafía/economía , Radiofármacos , Sensibilidad y Especificidad , Tomografía Computarizada Espiral/economía
3.
J Thromb Haemost ; 3(1): 17-25, 2005 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-15634261

RESUMEN

BACKGROUND: Spiral computed tomography (CT) has emerged as a potentially conclusive diagnostic test to exclude pulmonary embolism (PE) in patients with non-high probability scintigraphy and is already widely used-sometimes as the sole primary diagnostic test in the diagnosis of suspected PE. Its true sensitivity and specificity has, however, not been evaluated previously in a large cohort of consecutive patients. METHODS: In a multicenter prospective study 627 consecutive patients with clinically suspected PE were studied. Patients with normal perfusion scintigraphy were excluded from further analysis. Single-detector spiral CT scanning and ventilation scintigraphy were then performed in all patients to diagnose PE, while pulmonary angiography was performed as the gold standard. The only exceptions were those patients who had both a high-probability VQ scan and a CT scan positive for PE: these patients were considered to have PE and did not undergo additional pulmonary angiography. All imaging tests were read by independent expert panels. RESULTS: Five hundred and seventeen patients were available for complete analysis. The prevalence of PE was 32%. Spiral CT correctly identified 88 of 128 patients with PE, and 92 of 109 patients without PE, for a sensitivity and specificity of 69%[95% confidence interval (CI) 63-75] and 84% (95% CI 80-89), respectively. The sensitivity of spiral CT was 86% (95% CI 80-92) for segmental or larger PE and 21% (95% CI 14-29) in the group of patients with subsegmental PE. CONCLUSION: The overall sensitivity of spiral CT for PE is too low to endorse its use as the sole test to exclude PE. This holds true even if one limits the discussion to patients with larger PE in segmental or larger pulmonary artery branches. We conclude that, in patients with clinically suspected PE and an abnormal perfusion scintigraphy, single-slice detector spiral CT is not sensitive enough to be used as the sole test to exclude PE.


Asunto(s)
Embolia Pulmonar/diagnóstico por imagen , Embolia Pulmonar/diagnóstico , Tomografía Computarizada Espiral/métodos , Adulto , Anciano , Algoritmos , Angiografía/métodos , Estudios de Cohortes , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Masculino , Persona de Mediana Edad , Perfusión , Cintigrafía , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Tomografía Computarizada por Rayos X
4.
Neth J Med ; 59(4): 161-9, 2001 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-11578790

RESUMEN

In The Netherlands, the 'Dutch consensus strategy' was formulated in 1993 as a diagnostic strategy for patients with suspected pulmonary embolism. Four years after its introduction, the application of this strategy was investigated. A questionnaire was sent to the hospital management and the departments of internal medicine and pulmonology of all Dutch hospitals. In total, 384 questionnaires were sent out. The response rates of the internists and pulmonologists were 63 and 65%, respectively. The specialists reported to have followed the consensus strategy in 75% of the patients seen the month prior to the questionnaire. However, analysis of only the last patient with the suspicion of pulmonary embolism revealed that the consensus strategy was followed in 55 of the 162 patients. As well, an overuse and an underuse of the different diagnostic facilities was documented. Furthermore almost a quarter of the patients were treated without an ascertained diagnosis, whereas 11% were not treated despite an improper exclusion of venous thrombo-embolism. Compared to a survey in 1994, the use of the 'Dutch consensus strategy' has not improved dramatically. In 34% of the patients, the consensus strategy was strictly followed (i.e. without any additional investigation); however in 67% of the patients a proper diagnosis was achieved. In any diagnostic strategy, two aspects should be considered. First the availability of the different facilities. Second the acceptance of the strategy by the physicians, involved in the diagnosis of patients with clinically suspected pulmonary embolism.


Asunto(s)
Conferencias de Consenso como Asunto , Adhesión a Directriz/estadística & datos numéricos , Departamentos de Hospitales/normas , Medicina Interna/normas , Guías de Práctica Clínica como Asunto , Pautas de la Práctica en Medicina/estadística & datos numéricos , Embolia Pulmonar/diagnóstico , Neumología/normas , Algoritmos , Angiografía , Actitud del Personal de Salud , Competencia Clínica , Árboles de Decisión , Mal Uso de los Servicios de Salud/estadística & datos numéricos , Departamentos de Hospitales/estadística & datos numéricos , Humanos , Medicina Interna/educación , Países Bajos , Embolia Pulmonar/terapia , Neumología/educación , Cintigrafía , Encuestas y Cuestionarios , Ultrasonografía , Relación Ventilacion-Perfusión
5.
J Appl Physiol (1985) ; 91(5): 2213-23, 2001 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-11641364

RESUMEN

Pharmacokinetics and immunogenicity of six different recombinant human soluble p55 tumor necrosis factor (TNF) receptor I (sTNFR-I) constructs were evaluated in juvenile baboons. The constructs included either an sTNFR-I IgG1 immunoadhesin (p55 sTNFR-I Fc) or five different sTNFR-I constructs covalently linked to polyethylene glycol. The constructs were administered intravenously three times, and pharmacokinetics and immunogenicity were examined over 63 days. All of the constructs were immunogenic, with the exception of a 2.6-domain monomeric sTNFR-I. To evaluate whether the nonimmunogenic 2.6-domain monomeric construct could protect baboons against TNF-alpha-induced mortality, baboons were pretreated with 1, 5, or 10 mg/kg body wt and were compared with baboons receiving either placebo or 1 mg/kg body wt of the dimeric 4.0-domain sTNFR-I construct (n = 3 each) before lethal Escherichia coli bacteremia. The monomeric construct protected baboons and neutralized TNF bioactivity, although greater quantities were required compared with the dimeric 4.0-domain sTNFR-I construct. We conclude that E. coli-recombinant-derived human sTNFR-I constructs can be generated with minimal immunogenicity on repeated administration and still protect against the consequences of exaggerated TNF-alpha production.


Asunto(s)
Inmunoglobulina G/metabolismo , Papio/metabolismo , Receptores del Factor de Necrosis Tumoral/metabolismo , Secuencia de Aminoácidos , Animales , Recuento de Células Sanguíneas , Clonación Molecular , Citocinas/metabolismo , Ensayo de Inmunoadsorción Enzimática , Escherichia coli/genética , Etanercept , Semivida , Hemodinámica/fisiología , Humanos , Inmunoglobulina G/inmunología , Cinética , Datos de Secuencia Molecular , Polietilenglicoles , Receptores del Factor de Necrosis Tumoral/inmunología , Factor de Necrosis Tumoral alfa/farmacocinética , Factor de Necrosis Tumoral alfa/farmacología
6.
Neth J Med ; 57(4): 142-9, 2000 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-11006490

RESUMEN

Pulmonary embolism remains a complex diagnostic problem. Although accurate and cost-effective, the 'Dutch consensus' strategy is not widely applied. We assessed the availability and investment plans of the different facilities used in this strategy. Furthermore, the current and future availability of new diagnostic modalities was investigated. A questionnaire was sent to all Dutch hospitals. The questionnaire contained separate sections with questions for the hospital management and the medical practitioners at the departments of radiology, nuclear medicine, internal medicine and pulmonology. Five hundred and eighty-four questionnaires were sent out (response rate 68%). Forty-three percent of the hospitals had no nuclear medicine facility, 11% had no pulmonary angiography facility, and 59% had no spiral CT scan (SCTA). Forty-six percent of the responding hospitals had a nuclear medicine facility; and 5% used Technegas for ventilation studies. Strategies with SCTA were available in about 27% of the hospitals. Due to future investments this number will increase to approximately 55%. Strategies with Technegas were available in 2.4% of the hospitals, this number might increase to 25% if Technegas is proven accurate. The 'Dutch consensus' strategy is available in two-thirds of the hospitals. All other strategies were less feasible. Several equivalent strategies for diagnosing pulmonary embolism should be developed. These strategies should be accurate, widely available and accepted.


Asunto(s)
Diagnóstico por Imagen/estadística & datos numéricos , Accesibilidad a los Servicios de Salud/estadística & datos numéricos , Planificación Hospitalaria/estadística & datos numéricos , Embolia Pulmonar/diagnóstico , Algoritmos , Árboles de Decisión , Adhesión a Directriz/estadística & datos numéricos , Investigación sobre Servicios de Salud , Humanos , Países Bajos , Guías de Práctica Clínica como Asunto , Encuestas y Cuestionarios
7.
Radiology ; 215(1): 184-8, 2000 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-10751485

RESUMEN

PURPOSE: To evaluate the prevalence and anatomic distribution of pulmonary embolism (PE) in a group of consecutive patients clinically suspected of having PE. MATERIALS AND METHODS: Four hundred eighty-seven consecutive patients clinically suspected of having PE were examined in six Dutch hospitals from May 1997 through March 1998. Patients underwent ventilation-perfusion (V-P) scintigraphy, spiral computed tomographic (CT) angiography, and/or digital subtraction pulmonary angiography according to a strict diagnostic protocol. Independent readers reviewed all of the diagnostic image studies in centralized readings. The largest pulmonary arterial branch in which PE was detected was recorded. RESULTS: The prevalence of PE was 27% (130 of 487 patients). There was a significant difference in PE size between the high-probability and nondiagnostic V-P scans: The high-probability scans tended to depict larger emboli, but they also showed small subsegmental emboli. Twenty-nine (22%) of 130 patients had subsegmental PE; 23 of these 29 patients had a high-probability V-P scan. CONCLUSION: The largest pulmonary arterial branch with PE was central or lobar in 66 (51%), segmental in 35 (27%), and isolated subsegmental in 29 (22%) patients.


Asunto(s)
Embolia Pulmonar/diagnóstico , Adulto , Algoritmos , Angiografía/métodos , Angiografía de Substracción Digital , Distribución de Chi-Cuadrado , Estudios de Cohortes , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador/métodos , Pulmón/irrigación sanguínea , Pulmón/patología , Masculino , Persona de Mediana Edad , Países Bajos , Prevalencia , Probabilidad , Estudios Prospectivos , Embolia Pulmonar/diagnóstico por imagen , Embolia Pulmonar/patología , Cintigrafía , Tomografía Computarizada por Rayos X/métodos , Relación Ventilacion-Perfusión
8.
Clin Exp Rheumatol ; 17(5): 553-60, 1999.
Artículo en Inglés | MEDLINE | ID: mdl-10544838

RESUMEN

OBJECTIVE: To determine the potential combination benefit of treatment with PEG sTNF-RI and methotrexate in adjuvant arthritic rats. METHODS: Lewis rats with adjuvant arthritis were treated by sc injections of either 3.0 or 0.3 mg/kg PEG sTNF-RI on days 9, 11, and 13 of adjuvant arthritis. The effects of PEG sTNF-RI treatment alone were compared to treatment with daily oral methotrexate (0.075, 0.06 or 0.045 mg/kg) or methotrexate in combination with PEG sTNF-RI. Efficacy was monitored by volume measurement of ankle joints, final paw weights and histologic evaluation with particular emphasis on bone lesions. RESULTS: Treatment with 3.0 or 0.3 mg/kg PEG sTNF-RI alone resulted in 52% or 28% inhibition, respectively, of paw swelling as assessed by final paw weight. Treatment with methotrexate at either 0.075, 0.06, or 0.045 mg/kg gave 84%, 51% or 18% inhibition and combination treatment resulted in additive inhibitory effects. Histologic evaluation of ankle joints demonstrated 68% or 25% inhibition of bone resorption with PEG sTNF-RI alone at 3.0 or 0.3 mg/kg. Treatment with 0.075, 0.06 or 0.045 mg/kg methotrexate resulted in 98%, 76% or 40% inhibition of bone resorption. Additive benefit was best seen with the lower doses of methotrexate. CONCLUSION: Combination therapy with PEG sTNF-RI and methotrexate results in additive benefit, with the final result being excellent inhibition of all arthritis parameters. Data from these studies supports the clinical investigation of the use of combination therapy of PEG sTNF-RI and methotrexate in rheumatoid arthritis patients.


Asunto(s)
Antirreumáticos/farmacología , Artritis Experimental/tratamiento farmacológico , Metotrexato/farmacología , Polietilenglicoles/administración & dosificación , Receptores del Factor de Necrosis Tumoral/administración & dosificación , Animales , Artritis Experimental/patología , Peso Corporal , Quimioterapia Combinada , Inyecciones Subcutáneas , Masculino , Polietilenglicoles/farmacología , Ratas , Ratas Endogámicas Lew , Receptores Tipo I de Factores de Necrosis Tumoral , Esplenomegalia , Tarso Animal/patología , Receptores Señuelo del Factor de Necrosis Tumoral
9.
Inflamm Res ; 48(8): 453-60, 1999 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-10493163

RESUMEN

OBJECTIVE: To determine the potential combination benefit receptor of treatment with PEGylated soluble tumor necrosis factor type I (PEG sTNF-RI) and dexamethasone (dex) or indomethacin (indo) in adjuvant arthritic rats. SUBJECTS: 160 male Lewis Rats. TREATMENT: PEG sTNF-RI, dex, indo. METHODS: Rats with adjuvant arthritis were given daily oral dex (0.025 or 0.006 mg/kg) or indo (0.5 or 0.25 mg/kg) day 9-14, alone or in combination with PEG sTNF-RI (sc on days 9, 11, and 13 of arthritis). Efficacy was monitored by volume measurement of ankle joints, final paw weights and histologic evaluation with particular emphasis on bone lesions. RESULTS: Treatment with 1 mg/kg PEG sTNF-RI alone resulted in 27% inhibition of final paw weights, dex alone (0.025 mg/kg) gave 25% inhibition and the combination resulted in 58% inhibition. Histologic evaluation of ankle joints demonstrated 48% inhibition of bone resorption with PEG sTNF-RI alone, 55% inhibition with dex alone and the combination treatment inhibited bone resorption by 100%. Inactive doses of PEG sTNF-RI (0.3 mg/kg) and dex (0.006 mg/kg) when combined resulted in 39% inhibition of paw swelling (AUC) and 39% inhibition of bone resorption. Combination treatment with indomethacin resulted in slight additive effects on inflammation parameters but no additive effects on bone resorption. CONCLUSION: Combination therapy with PEG sTNF-RI and dexamethasone results in additive or synergistic effects depending on the dose. Combination therapy with indomethacin resulted in slight additive effects on paw swelling parameters, but no additive benefit on bone resorption. Data from these studies support the clinical investigation of the use of combination therapy of PEG sTNF-RI and dex or other corticosteroids in rheumatoid arthritis patients.


Asunto(s)
Antiinflamatorios no Esteroideos/uso terapéutico , Antiinflamatorios/uso terapéutico , Artritis Experimental/tratamiento farmacológico , Dexametasona/uso terapéutico , Indometacina/uso terapéutico , Polietilenglicoles/química , Receptores del Factor de Necrosis Tumoral/uso terapéutico , Animales , Artritis Experimental/patología , Resorción Ósea/tratamiento farmacológico , Sinergismo Farmacológico , Quimioterapia Combinada , Edema/patología , Pie/patología , Masculino , Ratas , Ratas Endogámicas Lew , Receptores del Factor de Necrosis Tumoral/química , Receptores Tipo I de Factores de Necrosis Tumoral , Receptores Señuelo del Factor de Necrosis Tumoral
10.
J Rheumatol ; 26(6): 1347-51, 1999 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-10381054

RESUMEN

OBJECTIVE: To determine the importance of tumor necrosis factor (TNF) in the pathogenesis of adjuvant disease in rats and to determine plasma levels of recombinant soluble TNF receptor type I (sTNF-RI) necessary for efficacy, to project dosing for human clinical trials. METHODS: Rats with adjuvant arthritis were treated by continuous infusion with sTNF-RI forms to maintain blood levels of this TNF-alpha inhibitory protein. In addition, rats were given bolus injections of polyethylene glycol linked sTNF-RI and efficacy and plasma levels were determined. Effects of treatment in the rats were monitored by sequential volume or diameter measurement of ankle joints, final paw weights, and histologic evaluation of ankle joints, with particular emphasis on bone erosive lesions. RESULTS: In all studies and regardless of dosing methodology (bolus vs continuous infusion), minimal plasma levels for efficacy were in the 0.3-0.5 microg/ml range. Higher plasma levels resulted in greater efficacy, with maximal effects achieved when plasma levels were in the 5 microg/ml range. Beneficial effects of treatment were seen on body weight, paw swelling, splenomegaly, hepatomegaly, and bone resorption. CONCLUSION: TNF-alpha is an important mediator of all aspects of rat adjuvant disease including both the destructive processes in the joints as well as the systemic manifestations of adjuvant disease. Studies using various forms of sTNF-RI consistently show that plasma levels of 0.3-0.5 microg/ml are required for minimal efficacy and that higher plasma levels show dose-responsive enhanced efficacy.


Asunto(s)
Antígenos CD/sangre , Antígenos CD/uso terapéutico , Artritis Experimental/sangre , Artritis Experimental/tratamiento farmacológico , Receptores del Factor de Necrosis Tumoral/sangre , Receptores del Factor de Necrosis Tumoral/uso terapéutico , Animales , Antígenos CD/administración & dosificación , Antígenos CD/metabolismo , Área Bajo la Curva , Artritis Experimental/patología , Peso Corporal/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Portadores de Fármacos , Inflamación/patología , Masculino , Tamaño de los Órganos/efectos de los fármacos , Polietilenglicoles/administración & dosificación , Polietilenglicoles/metabolismo , Ratas , Ratas Endogámicas Lew , Receptores del Factor de Necrosis Tumoral/administración & dosificación , Receptores del Factor de Necrosis Tumoral/metabolismo , Receptores Tipo I de Factores de Necrosis Tumoral , Tarso Animal/efectos de los fármacos , Tarso Animal/patología , Resultado del Tratamiento
12.
J Comput Assist Tomogr ; 22(3): 413-7, 1998.
Artículo en Inglés | MEDLINE | ID: mdl-9606382

RESUMEN

PURPOSE: The purpose of this work is to describe the spiral CT appearance of resolving clots at 6 week follow-up in patients with acute pulmonary embolism (PE). METHOD: Nineteen patients with acute PE initially identified with spiral CT scan underwent repeat CT examinations at 6 week follow-up after the start of anticoagulant therapy. The appearances of the clots on the initial CT scan and follow-up CT scan were analyzed. RESULTS: Normalization of the pulmonary arteries at follow-up was seen in six patients (32%) only. Residual abnormalities were present in 13 of 19 patients (68%). Resolving clots were seen as eccentric wall-adherent filling defects (22%) or filling defects with central contrast material (3%). CONCLUSION: Resolving clots after acute PE can be seen with follow-up CT scan in the majority of patients. It is important to be familiar with these findings.


Asunto(s)
Anticoagulantes/uso terapéutico , Heparina/uso terapéutico , Embolia Pulmonar/tratamiento farmacológico , Tomografía Computarizada por Rayos X/métodos , Enfermedad Aguda , Administración Oral , Adulto , Anciano , Anciano de 80 o más Años , Angiografía , Anticoagulantes/administración & dosificación , Arterias , Medios de Contraste , Femenino , Estudios de Seguimiento , Heparina/administración & dosificación , Humanos , Procesamiento de Imagen Asistido por Computador , Inyecciones Intravenosas , Pulmón/irrigación sanguínea , Pulmón/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Embolia Pulmonar/diagnóstico por imagen
13.
J Appl Physiol (1985) ; 84(4): 1119-30, 1998 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-9516174

RESUMEN

Immunogenicity, pharmacokinetics, and therapeutic efficacy of three novel dimeric soluble tumor necrosis factor (TNF)-receptor I constructs [TNF-binding protein (bp)] were evaluated in 28 baboons, 12 of which were healthy and 16 were challenged with a lethal Escherichia coli bacteremia. The three constructs differed only in the number of extracellular domains of the TNF receptor I and were dimerized with polyethylene glycol. Although all three constructs had generally similar pharmacokinetics when administered to a naive animal, they differed quantitatively in their immunogenicity. Antibodies were detected more frequently, and titers were significantly higher (P < 0.05) in both healthy and septic baboons that received the 4.0-domain TNF-bp construct, compared with animals receiving the 2.6-domain construct. When the TNF-bp constructs were administered a second time (21 days later), the half-lives of the three constructs were significantly shorter in animals that had an antibody response after the first injection. In contrast, all three TNF-bp constructs were equally effective at improving outcome, blocking a systemic TNF-alpha response, and attenuating the cytokine responses when administered at a dose of 1.0 mg/kg body wt 1 h before a lethal E. coli infusion. The findings suggest that immunogenicity of TNF-bp constructs can be altered by changing the number of functional domains, without affecting their capacity to neutralize TNF-alpha and to abrogate TNF-mediated pathology.


Asunto(s)
Bacteriemia/inmunología , Infecciones por Escherichia coli/inmunología , Receptores del Factor de Necrosis Tumoral/inmunología , Receptores del Factor de Necrosis Tumoral/metabolismo , Animales , Formación de Anticuerpos/fisiología , Bacteriemia/patología , Cristalografía por Rayos X , Infecciones por Escherichia coli/patología , Femenino , Semivida , Inmunoglobulina G/biosíntesis , Riñón/patología , Cinética , Recuento de Leucocitos , Masculino , Conformación Molecular , Papio , Unión Proteica
14.
Br J Radiol ; 71(852): 1260-5, 1998 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-10318998

RESUMEN

The purpose of this study was to determine the prevalence of lower extremity deep venous thrombosis (DVT) in patients with suspected and proven pulmonary embolism (PE). A meta-analysis was performed, based on literature from January 1983 to June 1997. Papers obtained from a computer-aided literature search were divided into studies with pulmonary angiography or ventilation-perfusion (V/Q) scintigraphy as the reference study. Our own observational data of the prevalence of DVT in 149 patients suspected of PE were also reported. The estimated prevalence of DVT in patients with proven and suspected PE was calculated. In the 149 patients studied, the prevalence of DVT was 12% with suspected PE and 32% (95% confidence interval 20-46%) in patients with proven PE. The individual studies showed a considerable heterogeneity, the prevalence of DVT in proven PE ranged from 10 to 93%. The pooled estimate of the prevalence of DVT in patients suspected of PE, over all studies, was 18% (95% confidence interval 15-20%). The DVT prevalence in proven PE was 36% (95% confidence interval 22-52%) in the angiography-based studies, and 45% (95% confidence interval 33-58%) in the V/Q scintigraphy-based studies. In conclusion, the current meta-analysis shows that the prevalence of DVT in suspected PE is approximately 18%, and in proven PE 36-45%.


Asunto(s)
Pierna/irrigación sanguínea , Embolia Pulmonar/complicaciones , Trombosis de la Vena/complicaciones , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Arteria Pulmonar/diagnóstico por imagen , Embolia Pulmonar/diagnóstico por imagen , Radiografía , Cintigrafía
16.
Arch Orthop Trauma Surg ; 116(4): 249-50, 1997.
Artículo en Inglés | MEDLINE | ID: mdl-9128785

RESUMEN

The clinical features of a superior dislocation of the glenohumeral joint are described. Reposition, even under general anaesthesia, cannot be achieved. Associated supraspinatus tear, acromioclavicular separation and the dislocated position of the humeral head can be clearly visualized.


Asunto(s)
Manipulación Ortopédica , Luxación del Hombro/terapia , Anciano , Anciano de 80 o más Años , Enfermedad Crónica , Femenino , Humanos , Radiografía , Rango del Movimiento Articular , Luxación del Hombro/diagnóstico por imagen , Luxación del Hombro/fisiopatología
17.
Radiology ; 201(2): 467-70, 1996 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-8888242

RESUMEN

PURPOSE: To assess the reliability of spiral computed tomographic (CT) angiography of the pulmonary arteries in the diagnosis of pulmonary embolism (PE). MATERIALS AND METHODS: One hundred forty-nine patients clinically suspected of having PE underwent spiral CT angiography and ventilation-perfusion (V-P) scintigraphy. Pulmonary angiography was also performed when the results of the V-P scan were indeterminate. Imaging results of spiral CT angiography were compared and validated against a normal perfusion scan in 40 patients, a high-probability scintigram in 53 patients, and a pulmonary angiogram in 56 patients. RESULTS: Spiral CT angiograms were of satisfactory diagnostic quality in all 149 patients. The sensitivity of spiral CT angiography for the detection of PE was 94% (64 of 68 patients) (observer 1) and 82% (56 of 68 patients) (observer 2), and the specificity was 96% (78 of 81 patients) (observer 2). Good interobserver agreement was obtained for spiral CT angiographic results (kappa = .774). Spiral CT angiography proved to be effective in the detection of PE in pulmonary arteries up to the segmental level but not in the smaller subsegmental branches. Isolated subsegmental PE accounted for three false-negative spiral CT angiographic results for both observers. CONCLUSION: Spiral CT angiography is an accurate method for the detection and exclusion of PE, with the exception of isolated subsegmental PE.


Asunto(s)
Arteria Pulmonar/diagnóstico por imagen , Embolia Pulmonar/diagnóstico por imagen , Tomografía Computarizada por Rayos X , Anciano , Angiografía , Femenino , Humanos , Masculino , Sensibilidad y Especificidad , Tomografía Computarizada por Rayos X/métodos , Relación Ventilacion-Perfusión
18.
Thorax ; 51(1): 23-8, 1996 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-8658363

RESUMEN

BACKGROUND: A study was carried out to evaluate the potential place of spiral volumetric computed tomography (SVCT) in the diagnostic strategy for pulmonary embolism. METHODS: In a prospective study 249 patients with clinical suspicion of pulmonary embolism were evaluated with various imaging techniques. In all patients a ventilation/perfusion (V/Q) scan was performed. Seventy seven patients with an abnormal V/Q scan underwent SVCT. Pulmonary angiography was then performed in all 42 patients with a non-diagnostic V/Q scan and in three patients with a high probability V/Q scan without emboli on the SVCT scan. Patients with an abnormal perfusion scan also underwent ultrasonography of the legs for the detection of deep vein thrombosis. RESULTS: One hundred and seventy two patients (69%) had a normal V/Q scan. Forty two patients (17%) had a non-diagnostic V/Q scan, and in five of these patients pulmonary emboli were found both by SVCT and pulmonary angiography. In one patient, although SVCT showed no emboli, the angiogram was positive for pulmonary embolism. In one of the 42 patients the SVCT scan showed an embolus which was not confirmed by pulmonary angiography. The other 35 patients showed no sign of emboli. Thirty five patients (14%) had a high probability V/Q scan, and in 32 patients emboli were seen on SVCT images. Two patients had both a negative SVCT scan and a negative pulmonary angiogram. In one who had an inconclusive SVCT scan pulmonary angiography was positive. The sensitivity for pulmonary embolism was 95% and the specificity 97%; the positive and negative predicted values of SVCT were 97% and 97%, respectively. CONCLUSIONS: SVCT is a relatively noninvasive test for pulmonary embolism which is both sensitive and specific and which may serve as an alternative to ventilation scintigraphy and possibly to pulmonary angiography in the diagnostic strategy for pulmonary embolism.


Asunto(s)
Pulmón/diagnóstico por imagen , Embolia Pulmonar/diagnóstico por imagen , Tomografía Computarizada por Rayos X , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Evaluación como Asunto , Femenino , Humanos , Pulmón/fisiopatología , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Estudios Prospectivos , Arteria Pulmonar/diagnóstico por imagen , Cintigrafía , Sensibilidad y Especificidad , Tromboflebitis/diagnóstico por imagen , Ultrasonografía
19.
Ann Rheum Dis ; 49(1): 7-11, 1990 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-2310235

RESUMEN

To evaluate the ability of magnetic resonance imaging (MRI) to detect shoulder abnormalities 18 patients (36 shoulders) with rheumatoid arthritis (RA) and shoulder complaints were studied. Osseous abnormalities of the glenoid and humeral head were readily detected with MRI. The imaging planes used were not suitable for the evaluation of acromioclavicular joint involvement. Magnetic resonance imaging depicted soft tissue abnormalities that were not clearly visualised by plain film radiography, such as involvement of rotator cuff tendons and subacromial bursae, joint effusion, and muscular atrophy. Magnetic resonance imaging appears to be a sensitive method for evaluation of glenohumeral joint changes in patients with RA.


Asunto(s)
Artritis Reumatoide/patología , Imagen por Resonancia Magnética , Articulación del Hombro/patología , Adulto , Anciano , Artritis Reumatoide/diagnóstico por imagen , Estudios de Evaluación como Asunto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Radiografía , Articulación del Hombro/diagnóstico por imagen
20.
AJR Am J Roentgenol ; 150(5): 1083-7, 1988 May.
Artículo en Inglés | MEDLINE | ID: mdl-3258710

RESUMEN

Posttrauma damage due to anterior glenohumeral joint dislocation may result in recurrent dislocation. Currently CT arthrography is the method of choice to evaluate the extent of osseous and soft-tissue changes before reconstructive surgery. This study was undertaken to determine if MR was able to depict postdislocation abnormalities and if MR is a possible replacement for CT arthrography. Thirteen patients with recurrent anterior shoulder dislocation were evaluated with conventional radiography and MR; CT arthrography was performed in 10. Twelve patients underwent surgery, and the findings of MR and CT arthrography were verified. MR and CT arthrography showed the integrity of the glenoid labrum equally well. All humeral head defects, detected in nine patients with plain film radiography and CT, were easily identified with MR. Information about anterior joint capsule abnormalities is difficult to obtain with MR. However, separation of the capsule from the bony glenoid can be detected if a joint effusion is present to adequately distend the joint. Preliminary results of this study indicate that MR is useful in the assessment of postdislocation abnormalities and may possibly replace CT arthrography in the evaluation of patients with recurrent shoulder dislocation.


Asunto(s)
Imagen por Resonancia Magnética , Luxación del Hombro/diagnóstico , Articulación del Hombro/patología , Tomografía Computarizada por Rayos X , Humanos , Recurrencia , Luxación del Hombro/diagnóstico por imagen , Articulación del Hombro/diagnóstico por imagen
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