RESUMEN
Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease in children and uveitis is its most important extra-articular manifestation. Evidence-based recommendations are available only to a limited extent and therefore JIA associated uveitis management is mostly based on physicians experience. Consequently, treatment practices differ widely, both nationally and internationally. Therefore, an effort to optimize and publish recommendations for the care of children and young adults with rheumatic diseases was launched in 2012 as part of the international project SHARE (Single Hub and Access Point for Pediatric Rheumatology in Europe) to facilitate clinical practice for paediatricians and (paediatric) rheumatologists. The aim of this work was to translate published international SHARE recommendations for the diagnosis and treatment of JIA associated uveitis and to adapt them for use in the Czech and Slovak Republics. International recommendations were developed according to the standard methodology of the European League against Rheumatism (EULAR) by a group of nine experienced paediatric rheumatologists and three experts in ophthalmology. It was based on a systematic literature review and evaluated in the form of an online survey and subsequently discussed using a nominal group technique. Recommendations were accepted if > 80% agreement was reached (including all three ophthalmologists). A total of 22 SHARE recommendations were accepted: 3 on diagnosis, 5 on disease activity assessment, 12 on treatment and 2 on future recommendations. Translation of the original text was updated and modified with data specific to the czech and slovak health care systems and supplemented with a proposal for a protocol of ophthalmological dispensarization of paediatric JIA patients and a treatment algorithm for JIA associated uveitis. Conclusion: The aim of the SHARE initiative is to improve and standardize care for paediatric patients with rheumatic diseases across Europe. Therefore, recommendations for the diagnosis and treatment of JIA-associated uveitis have been formulated based on the evidence and agreement of leading European experts in this field.
Asunto(s)
Artritis Juvenil , Uveítis , Artritis Juvenil/complicaciones , Artritis Juvenil/diagnóstico , Artritis Juvenil/terapia , Niño , República Checa/epidemiología , Europa (Continente) , Humanos , Eslovaquia/epidemiología , Uveítis/diagnóstico , Uveítis/epidemiología , Uveítis/etiología , Adulto JovenRESUMEN
To elucidate the metabolism of islet amyloid polypeptide (IAPP) with respect to a possible renal elimination we investigated IAPP levels in 20 lean, nondiabetic patients with renal failure maintained on chronic hemodialysis (HD) and in 20 healthy controls. The basal levels of IAPP were significantly higher in uremic patients than in controls (15.1 +/- 3.2 vs. 3.2 +/- 0.2 pM, P < 0.001) suggesting renal excretion of IAPP. To investigate the impact of chronically elevated levels of endogenous IAPP on insulin secretion and insulin sensitivity, a frequently sampled intravenous glucose tolerance test (FSIGT) was performed in a subset of patients on hemodialysis and in age-matched healthy controls (C) and obese patients with normal (NGT) and with impaired glucose tolerance (IGT). Insulin sensitivity index (SI) was 8.7 +/- 1.5 in C (P < 0.05 vs. NGT, P < 0.01 vs. IGT), 5.4 +/- 0.9 in HD (P < 0.05 vs. IGT), 3.1 +/- 1.0 in NGT, and 2.0 +/- 0.5 in IGT. First phase insulin secretion was increased in patients on HD compared with those of several control groups. The results of this study therefore indicate a renal route of metabolism of IAPP. Increased endogenous circulating IAPP levels over a long period of time do not lead to a decrease in insulin release in patients on HD and do not cause the insulin resistance commonly seen in obesity and diabetes. Increased levels of circulating IAPP therefore are not likely to be a pathogenetic factor in the development of non-insulin-dependent diabetes mellitus (NIDDM).
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Amiloide/sangre , Insulina/metabolismo , Fallo Renal Crónico/sangre , Adulto , Diabetes Mellitus Tipo 2/etiología , Prueba de Tolerancia a la Glucosa , Humanos , Secreción de Insulina , Polipéptido Amiloide de los Islotes Pancreáticos , Persona de Mediana EdadRESUMEN
PURPOSE: To compare hematologic recovery in patients receiving allogeneic blood cell transplantation (BCT) with those receiving allogeneic bone marrow transplantation (BMT). PATIENTS AND METHODS: One hundred eleven patients with leukemia in the early stages and with HLA-matched sibling donors were randomized in this study. One hundred one underwent transplantation. Standard procedures for collection and transplantation were used. Patients did not receive prophylactic granulocyte colony-stimulating factor after undergoing transplantation. In addition to clinical end points being established, a prospective and comparative economic evaluation of the first 6 months after transplantation was performed. RESULTS: Groups were balanced for patient, donor, and transplant characteristics. Blood cell collection led to the collection of a higher number of CD34(+) and CD3(+) cells than did bone marrow collection (P < 10(-6)) without reported side effects for the donor. Patients in the BCT group reached platelet counts of 25 and 50 x 10(9) platelets/L 8 and 11 days earlier than did the BMT group (P < 10(-4) and P < 10(-5)), respectively. This resulted in fewer platelet transfusions during the first 180 days after transplantation (P =.002) for the former group. The time to reach neutrophil counts of 0.5 and 1 x 10(9) neutrophils/L was 6 and 7 days shorter, respectively, in the BCT group than in the BMT group (P < 10(-5)). This quicker hematologic recovery was associated with a shorter length of hospitalization and a decrease in total cost of procedure during the first 6 months. CONCLUSION: This study establishes that allogeneic BCT results in quicker hematologic recovery but is associated with a higher occurrence of chronic graft-versus-host disease.
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Adyuvantes Inmunológicos/uso terapéutico , Trasplante de Médula Ósea/métodos , Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Trasplante de Células Madre Hematopoyéticas/métodos , Leucemia/terapia , Enfermedad Aguda , Adulto , Trasplante de Médula Ósea/economía , Trasplante de Médula Ósea/inmunología , Femenino , Trasplante de Células Madre Hematopoyéticas/economía , Humanos , Lenograstim , Leucemia/sangre , Leucemia/inmunología , Leucemia Mielógena Crónica BCR-ABL Positiva/sangre , Leucemia Mielógena Crónica BCR-ABL Positiva/inmunología , Leucemia Mielógena Crónica BCR-ABL Positiva/terapia , Leucemia Mieloide/sangre , Leucemia Mieloide/inmunología , Leucemia Mieloide/terapia , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/sangre , Leucemia-Linfoma Linfoblástico de Células Precursoras/inmunología , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Pronóstico , Estudios Prospectivos , Proteínas Recombinantes/uso terapéuticoRESUMEN
OBJECTIVES: This study sought to test the hypothesis that big endothelin-1 plasma levels in advanced heart failure are related to survival. BACKGROUND: In heart failure, production of the potent vasoconstrictor endothelin-1 is increased. Because elevation of immunoreactive endothelin-1 in severe heart failure is primarily related to the precursor "big" endothelin-1, increased big endothelin-1 levels may be associated with a poor prognosis. METHODS: Plasma big endothelin-1 concentrations, in addition to 16 clinical, hemodynamic and neurohumoral variables, were obtained from 113 patients (mean age -=/[SEM] 53 +/- 1 years) with left ventricular ejection fraction <20% and were related to 1-year mortality by a stepwise Cox regression multivariate analysis. RESULTS: Plasma big endothelin-1 concentrations were significantly higher in patients with moderate and severe heart failure than in those with mild heart failure (4.5 +/- 0.4 and 6.0 +/- 0.1 vs. 2.7 +/- 0.1 fmol/ml, p = 0.0001, respectively) and lower in 58 one-year survivors than in 29 nonsurvivors (2.6 +/- 0.1 vs. 5.9 +/- .04 fmol/ml, p = 0.0001) and 26 heart transplant recipients. By univariate analysis, big endothelin-1 plasma concentrations (p < 0.0001), functional class, daily furosemide dose, left ventricular ejection fraction, most hemodynamic variables and plasma atrial natriuretic peptide, sodium renin activity and aldosterone levels were all related to mortality, but only functional class provided additional prognostic information when big endothelin-1 plasma levels were entered into the multivariate model. CONCLUSIONS: In advanced heart failure, plasma big endothelin-1 is strongly related to survival and appears to predict 1-year mortality better than hemodynamic variables and levels of atrial natriuretic peptide, an established neurohumoral prognostic marker in chronic heart failure.
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Factor Natriurético Atrial/sangre , Endotelinas/sangre , Insuficiencia Cardíaca/sangre , Hemodinámica , Precursores de Proteínas/sangre , Adulto , Anciano , Endotelina-1 , Femenino , Insuficiencia Cardíaca/mortalidad , Insuficiencia Cardíaca/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Índice de Severidad de la Enfermedad , Análisis de SupervivenciaRESUMEN
The importance of the brain A2A adenosine receptor (A(2A)AR) in movement disorders urges the development of radiolabeled ligands for imaging those receptors by positron emission tomography (PET). This study evaluated one class of A(2A)AR antagonists, derivatives of 4-amino-6-benzylamino-1,2-dihydro-2-phenyl-1,2,4-triazolo[4,3-a]quinoxalin-2H-1-one, 10a, as agents for imaging brain A(2A)ARs by PET.. Modifications of a literature synthesis of 10a efficiently generated analogs 10b-s for pharmacological evaluation. Radioligand binding experiments showed affinities for the rat brain A(2A)AR in the low nanomolar range but similar affinities for the A1AR and substantial unspecific binding. Autoradiography employing [3H]10a, showing that high unspecific binding obscured specific binding to both the A1AR and A(2A)AR. Thus, compounds 10b-s are unsuitable as ligands for imaging brain A(2A)ARs by PET.
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Antagonistas del Receptor de Adenosina A2 , Quinoxalinas/síntesis química , Triazoles/síntesis química , Animales , Autorradiografía , Unión Competitiva/fisiología , Encéfalo/diagnóstico por imagen , Ligandos , Espectroscopía de Resonancia Magnética , Estructura Molecular , Tomografía de Emisión de Positrones/métodos , Quinoxalinas/química , Quinoxalinas/farmacología , Ensayo de Unión Radioligante , Ratas , Espectrometría de Masa por Ionización de Electrospray , Triazoles/química , Triazoles/farmacología , TritioRESUMEN
Resumen Introducción: El cáncer laríngeo es una de las neoplasias de cabeza y cuello más frecuentes, asociado al envejecimiento y a los hábitos de vida. Los análisis de supervivencia de cáncer laríngeo en Chile son escasos. Objetivo: Calcular y analizar la supervivencia y las características clínicas del cáncer laríngeo en pacientes del Servicio de Otorrinolaringología del Hospital Carlos Van Buren, Valparaíso, Chile. Material y Método: Se realizó un estudio retrospectivo de cohorte, incluyendo pacientes diagnosticados con carcinoma escamoso de laringe entre 2007 y 2018. Se calculó la supervivencia con el método de Kaplan-Meier. Se aplicaron las pruebas de log rank, t de Student y exacta de Fisher. Resultados: Se incluyeron 211 pacientes, 90,52% hombres, con un promedio de edad de 68 años. El factor de riesgo más frecuente fue el tabaquismo. La ubicación tumoral más frecuente fue la glotis (59,44%) y el motivo de consulta más común la disfonía (52,66%). Un 70,48% presentó estadios avanzados. En 23,92% se realizó laringectomía total como tratamiento primario. La supervivencia global a 2 años fue de 86,6% en estadio precoz y 45,2% en estadio avanzado, mientras que a 5 años fue de 77,4% y 33%, respectivamente. Conclusión: La supervivencia estimada fue menor que en otros estudios nacionales, lo que puede asociarse al tamaño de la muestra analizada, a factores etarios y/o a mayor latencia de inicio de tratamiento. Se enfatiza el mejoramiento de los registros clínicos y la gestión sanitaria para un manejo oportuno.
Abstract Introduction: Laryngeal carcinoma is one of the most frequent head and neck neoplasms, being associated with ageing and lifestyles. In Chile, survival analyses of laryngeal carcinoma are scarce. Aim: To estimate and analyze the survival and clinical characteristics of laryngeal carcinoma in patients attended at the Otorhinolaryngology Department of the Carlos Van Buren Hospital, Valparaíso, Chile. Material and Method: We conducted a retrospective cohort study, including patients diagnosed with laryngeal squamous cell carcinoma between 2007 and 2018. Kaplan-Meier estimator was applied for survival analysis. Log rank test, Student's t-test and Fisher's exact test were applied. Results: 211 patients were included, 90,52% were men, with an average age of 68 years. The main risk factor was smoking (80%). The most frequent tumor location was in the glottis (59,44%) and the most frequent reason for consultation was dysphonia (52,66%). Most cases (70,48%) presented at advanced stages. Laryngectomy was performed as a primary treatment in 23,92%. The 2-year overall survival rate was 86,6% for early stages and 45,2% for advanced stages; the 5-year overall survival rate was 77,4% and 33%, respectively. Conclusion: The estimated survival rate was lower than those referred by other national studies, which may be associated with the analyzed sample size, age-related factors and/or period of latency until the beginning of treatment. We emphasize the necessity of an improvement in clinical records and the health management to the timely treatment.
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Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/epidemiología , Neoplasias Laríngeas/mortalidad , Neoplasias Laríngeas/epidemiología , Chile/epidemiología , Neoplasias Laríngeas/terapia , Tasa de Supervivencia , Estudios RetrospectivosRESUMEN
A number of natural and synthetic sugar analogues have been tested for their antiviral activity, using an influenza virus strain as a model. Hemagglutinating titres (HA) and cytopathic effect (CPE) were surveyed to estimate the virus production. It was found that introduction of the benzyl group into these sugars generally causes them to become antivirally active. Substitution with methyl, acetyl, uridyl and thiocyanyl groups or derivatization with azido, isopropylidene and benzylidene groups were without effect. All sugars containing the 2-deoxy-2-acetamido group were inactive.
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Antivirales/farmacología , Carbohidratos/farmacología , Virus de la Influenza A/efectos de los fármacos , Animales , Carbohidratos/síntesis química , Línea Celular , Efecto Citopatogénico Viral , Perros , Hemaglutinación por Virus , Virus de la Influenza A/crecimiento & desarrollo , Riñón , Replicación Viral/efectos de los fármacosRESUMEN
Plasma endothelin concentrations were evaluated in 53 chronic, congestive heart failure (CHF) patients with or without history of systemic hypertension, as well as in 9 with hypertension only and in 22 healthy control subjects. Plasma renin, aldosterone and atrial natriuretic peptide, as well as clinical and hemodynamic data were determined. In patients with CHF, big endothelin-1 was, independent of hypertension history, significantly greater than in hypertensive patients with normal cardiac function and in control subjects (both p < 0.0001). Patients with severe CHF had significantly greater big endothelin-1 values than did those with moderate CHF. During 12-month follow-up, 11 patients with CHF underwent heart transplantation, and 9 died; these patients had significantly greater big endothelin-1 concentrations than did the 33 clinically stable patients (p < 0.001). Big endothelin-1 and atrial natriuretic peptide correlated with right atrial pressure, pulmonary capillary wedge pressure, left ventricular ejection fraction, effort capacity and severity of CHF (New York Heart Association functional class).
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Endotelinas/sangre , Insuficiencia Cardíaca/sangre , Hipertensión/sangre , Adulto , Anciano , Aldosterona/sangre , Factor Natriurético Atrial/sangre , Estudios de Casos y Controles , Femenino , Estudios de Seguimiento , Insuficiencia Cardíaca/complicaciones , Insuficiencia Cardíaca/fisiopatología , Hemodinámica , Humanos , Hipertensión/complicaciones , Hipertensión/fisiopatología , Masculino , Persona de Mediana Edad , Pronóstico , Renina/sangreRESUMEN
BACKGROUND: Prostaglandins of the E type are potent endogenous vasodilators that also interfere with the activity of the sympathetic nervous system. Thus treating patients with end-stage heart failure with prostaglandin E1 (PGE1) infusions seems to accord well with the hypothesis that neurohumoral imbalance rather than hemodynamic derangements should be the priority in the treatment of heart failure. METHODS: We sought to investigate neurohumoral in addition to hemodynamic changes during long-term PGE1 infusion and determined plasma renin activity, atrial natriuretic peptide, norepinephrine, and big endothelin plasma levels in 13 male patients with heart failure whose symptoms remained severe in spite of optimized oral therapy with digitalis, nitrates, furosemide (185 +/- 72 mg/d) and enalapril (33 +/- 3 mg/d). PGE1 infusion rate was started with 2.5 ng/kg/min and stepwise increased to the maximum tolerated dose (26 +/- 4 ng/kg/min), which was halved for continuous infusion through the following 12 hours and further stepwise reduced to an average dose of 8 +/- 1 ng/kg/min. Right heart catheterization was performed for acute hemodynamic studies and after 4 weeks. All patients were discharged with a catheter that was connected to a portable pump for home therapy. RESULTS: Acute effects of PGE1 were reductions in systemic blood pressure, (p < 0.05), right atrial pressure (p < 0.001), pulmonary artery pressure (p < 0.05), pulmonary capillary wedge pressure (p < 0.01), systemic and pulmonary vascular resistance index (both p < 0.01) and an increase in cardiac and stroke volume index (both p < 0.001) without a change in heart rate. After 4 weeks a persistent increase from baseline in cardiac index (from 1.9 +/- 0.1 to 2.5 +/- 0.2 L/min/m2; p < 0.01) and in pulmonary vascular resistance index (from 479 +/- 50 to 331 +/- 29 dynes x sec/cm5 x m2; p < 0.05) was observed. Atrial natriuretic peptide (p < 0.05) decreased, and norepinephrine and big endothelin showed a tendency to a lower level. Concomitantly, New York Heart Association functional class changed (p = 0.0001), with one patient's condition remaining class IV, the conditions of seven patients decreasing to class II, and the conditions of five patients decreasing to class III. CONCLUSION: Thus long-term parenteral home therapy with PGE1 infusions in patients with severe end-stage heart failure elicited beneficial clinical and hemodynamic effects without activating neurohumoral counterregulatory systems.
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Alprostadil/uso terapéutico , Atención Ambulatoria , Insuficiencia Cardíaca/tratamiento farmacológico , Vasodilatadores/uso terapéutico , Cateterismo Cardíaco , Estudios de Factibilidad , Insuficiencia Cardíaca/sangre , Insuficiencia Cardíaca/fisiopatología , Hemodinámica/efectos de los fármacos , Humanos , Masculino , Persona de Mediana Edad , Neurotransmisores/sangre , Proyectos Piloto , Índice de Severidad de la EnfermedadRESUMEN
Blood cell transplantation (BCT) is now common practice in the autologous setting. We performed a pilot study of allogeneic BCT, collected after the priming of an HLA-identical sibling with a glycosylated rhu-G-CSF (lenograstim) (10 microg/kg). Fifty-four patients were included (38 +/- 11; M/F = 33/21; CML (n = 17), AML (n = 14), ALL (n = 15); MDS (n = 8)). Transplant procedures were standard (TBI regimen = 47 (87%); MTX-CsA: n = 37; CsA-PDN: n = 17). No serious adverse events were reported in donors. A median of 11 (3.5-29.1) x 10(6)/kg CD34+ cells, 332 (33-820) x 10(6)/kg CD3+ cells were collected. Four patients did not engraft (early death: n = 2; graft failure: n = 2). Fifty-one patients initially recovered 0.5 x 10(9)/l ANC and 25 x 10(9)/l platelets at 15 (10-30) and 13 (9-188) days. 29/51 and 29/38 experienced grade > or =2 acute and chronic GVHD. With a median follow-up of 25 months (18-36), relapse rate is 16% +/- 8, survival and DFS probabilities are similar (50% +/- 13). A better outcome is documented for patients under 45 years and in the early phase of the disease (n = 28), with an identical survival and DFS of 71% +/- 13. In conclusion, lenograstim is a potent rhu-G-CSF for mobilisation of allogeneic hematopoietic progenitors. Two-year follow-up indicates good haematological recovery but some concerns about graft failure and chronic GVHD have arisen deserving prospective evaluation.
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Adyuvantes Inmunológicos/farmacología , Factor Estimulante de Colonias de Granulocitos/farmacología , Neoplasias Hematológicas/terapia , Movilización de Célula Madre Hematopoyética , Trasplante de Células Madre Hematopoyéticas , Adolescente , Adulto , Femenino , Prueba de Histocompatibilidad , Humanos , Lenograstim , Masculino , Persona de Mediana Edad , Proyectos Piloto , Proteínas Recombinantes/farmacología , Análisis de Supervivencia , Donantes de Tejidos , Trasplante HomólogoRESUMEN
In refractory temporal lobe epilepsy (TLE) temporal lobe structures and functions are continuously or intermittently affected by abnormal brain electrical events, noxious neurochemical agents, and metabolic disturbances. There is conflicting evidence regarding the relationship between the duration of refractory mesial TLE and quantitative measures of temporal lobe functions and volumes of the hippocampi. Twenty patients (aged 28 +/- 7 years, 14 males) with an initial precipitating injury before the age of 5 years were subjected to high-resolution magnetic resonance imaging, fluoro-2-deoxy-d-glucose positron-emission tomography (PET), and the Wada test. We investigated whether the duration of unilateral refractory TLE (12 left, 8 right) affects hippocampal volume, glucose metabolism, or Wada hemispheric memory performance. Ipsilateral to the epileptogenic zone the hippocampal volume, metabolism, and Wada hemispheric memory performance were reduced compared to the corresponding contralateral measures. The duration of epilepsy controlled for age at investigation, side of seizure origin, underlying cause, and sex were negatively correlated with ipsi- and contralateral hippocampal volume, hippocampal metabolism, and Wada hemispheric memory performance. Moreover, ipsilateral Wada hemispheric memory performance and contralateral hippocampal glucose metabolism were correlated with the frequency of habitual seizures. Refractory TLE seems to be associated with a slow but ongoing bilateral temporal lobe damage. These cross-sectional results require verification by longitudinal studies carried out over a period of more than two decades.
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Epilepsia del Lóbulo Temporal/diagnóstico , Epilepsia del Lóbulo Temporal/metabolismo , Glucosa/metabolismo , Hipocampo/diagnóstico por imagen , Hipocampo/patología , Memoria , Adolescente , Adulto , Estudios Transversales , Epilepsia del Lóbulo Temporal/psicología , Femenino , Fluorodesoxiglucosa F18 , Humanos , Imagen por Resonancia Magnética , Masculino , Pruebas Neuropsicológicas , Radiografía , Radiofármacos , Factores de Tiempo , Tomografía Computarizada de EmisiónRESUMEN
Patients with mesial temporal lobe epilepsy (mTLE) exhibit marked depressions of the regional cerebral glucose metabolism (rCMRGlu) in the mesiotemporal region. We hypothesised that patients with temporal lobe epilepsy (TLE) who have a bilateral somatosensory or acoustic ( = temporolateral/SII-) aura can be differentiated from mTLE by rCMRGlu depressions primarily involving temporo-perisylvian locations. We therefore used this ictal semiology as a clinical criterion to define a subgroup of such patients and measured the rCMRGlu in 16 patients with TLE as evident from interictal and ictal EEG-video monitoring. Clinically, they presented with medically refractory complex partial seizures and were subjected to presurgical evaluation. The pattern of the interictal rCMRGlu in the TLE patients was different from that observed in patients with mTLE and showed significant depressions ipsilateral to the epileptic focus in mesial temporal and lateral temporal regions but spared the thalamus. The neocortical metabolic depressions were spatially more extended in right than in left TLE patients. Magnetic resonance images (MRI) were either normal (n = 5) or revealed unilateral or bilateral hippocampal atrophy/sclerosis (n = 7), or temporal or extratemporal focal cortical dysplasia (n = 4). The selected TLE patients presented here comprise a heterogeneous group showing most pronounced metabolic depressions in the lateral temporal cortex. Thus, our data suggest that non-invasive metabolic imaging can assist in identifying the neocortical symptomatogenic zone in putative temporo-perisylvian lobe epilepsy.
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Trastornos de la Percepción Auditiva/etiología , Epilepsia Parcial Compleja/metabolismo , Epilepsia Parcial Sensorial/metabolismo , Epilepsia del Lóbulo Temporal/metabolismo , Glucosa/metabolismo , Lóbulo Temporal/metabolismo , Abdomen , Adolescente , Adulto , Atrofia , Corteza Auditiva/diagnóstico por imagen , Corteza Auditiva/metabolismo , Corteza Auditiva/patología , Niño , Dominancia Cerebral , Epilepsia , Epilepsia Parcial Compleja/diagnóstico por imagen , Epilepsia Parcial Compleja/patología , Epilepsia Generalizada/diagnóstico por imagen , Epilepsia Generalizada/metabolismo , Epilepsia Generalizada/patología , Epilepsia Parcial Sensorial/diagnóstico por imagen , Epilepsia Parcial Sensorial/patología , Epilepsia del Lóbulo Temporal/diagnóstico por imagen , Epilepsia del Lóbulo Temporal/patología , Epilepsia Tónico-Clónica/diagnóstico por imagen , Epilepsia Tónico-Clónica/metabolismo , Epilepsia Tónico-Clónica/patología , Femenino , Hipocampo/diagnóstico por imagen , Hipocampo/patología , Humanos , Imagen por Resonancia Magnética , Masculino , Parestesia/etiología , Esclerosis , Lóbulo Temporal/diagnóstico por imagen , Lóbulo Temporal/patología , Tomografía Computarizada de EmisiónRESUMEN
A pathophysiological role for endothelin (ET), one of the most potent vasoconstrictor peptides, has been suggested in ATN and during kidney allograft rejection. As ET is known to have predominantly local effects, we investigated intrarenal ET content in 82 kidney transplant biopsies and 10 normal control kidneys. ET-immunostaining, using a polyclonal anti-ET-1 antibody was investigated in 4 intrarenal vascular beds (glomeruli, capillaries, arterioles, arteries) and in tubular epithelium. Normal kidneys showed a strong staining of endothelial cells in all vessels and of tubular epithelium. In biopsies with signs for acute vascular rejection a marked decrease in ET staining intensity was seen. In contrast, normal staining similar to control kidneys was detected in interstitial rejection and in ATN. The presence of chronic CyA toxicity, however, lead to a significant reduction of endothelial ET staining. Neither mean doses nor trough levels of CyA correlated closely with the immunostaining findings. Plasma big-ET levels were elevated during vascular rejection, but not in interstitial rejection and ATN. This study demonstrates a significant reduction of ET immunostaining in intrarenal vascular endothelium of kidney transplant biopsies showing signs of endothelial damage. In vascular allograft rejection these changes are often associated with a concomitant rise in plasma ET levels. Our findings support a postulated role of ET in vascular rejection and during CyA toxicity and show that endothelial damage, independent of its genesis, can lead to a reduction of intrarenal ET content.
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Endotelinas/fisiología , Rechazo de Injerto/patología , Trasplante de Riñón/inmunología , Riñón/patología , Adulto , Biopsia , Ciclosporina/efectos adversos , Ciclosporina/uso terapéutico , Endotelinas/análisis , Endotelio Vascular/patología , Rechazo de Injerto/epidemiología , Humanos , Inmunohistoquímica , Terapia de Inmunosupresión , Riñón/química , Trasplante de Riñón/patología , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
Several proteins from nacre of the oyster Pinctada maxima and the abalone Haliotis tuberculata were extracted and partly characterized. Proteins dispersed in aragonite were solubilized during demineralization with acetic acid whereas proteins adsorbed on conchiolin were extracted with sodium dodecyl sulfate and beta-mercaptoethanol. The matrix of Pinctada maxima nacre is composed of one main protein with an apparent molecular weight of 20 kDa (p20). This protein was found in the acetic acid soluble fraction of nacre, as well as in the Laemmli-solubilized extract of conchiolin. In addition, the p20 solubilized with acetic acid can form oligomers made of 6 monomers linked together by disulfide bridges. The first N-terminal 21 amino acids of p20 were determined and no homology with known proteins was found. In Haliotis tuberculata nacre, 5 main proteins were solubilized during demineralization and 3 glycoproteins were detected. Stains-all and Alcian blue staining revealed polyanionic proteins in the extracts isolated from Pinctada maxima and Haliotis tuberculata nacre.
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Glicoproteínas/aislamiento & purificación , Músculos/química , Ostreidae/química , Secuencia de Aminoácidos , Animales , Cromatografía Líquida de Alta Presión , Electroforesis en Gel de Poliacrilamida , Glicoproteínas/análisis , Datos de Secuencia Molecular , Peso Molecular , Solubilidad , Sulfatasas/farmacología , Tripsina/farmacologíaRESUMEN
nn small cell lung cancer, the main treatment modality is chemotherapy, combinated with early thoracic radiation therapy for patients with complete response. The treatment of relapse with chemotherapy is efficient. The precocity of the response after initiating multimodality treatment is the main prognosis factor. The prophylactic cranial irradiation reduce the frequency of brain metastases, but has no significant effect on survival. Patients with very limited small cell lung cancer (TNM stage I and II) can be managed by surgery. Association with colony stimulating factors can lessen the severity of neutropenic and infectious episodes. The role of maintenance therapy by interferon alpha in clinically disease free patients is suggested.
Asunto(s)
Carcinoma de Células Pequeñas/terapia , Neoplasias Pulmonares/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Carcinoma de Células Pequeñas/tratamiento farmacológico , Carcinoma de Células Pequeñas/radioterapia , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/radioterapia , Invasividad Neoplásica , Recurrencia Local de NeoplasiaRESUMEN
In a prospective study the authors compared the clinical, radiological, biochemical and diagnostic features of Pneumocystis carinii pneumonia (PCP) in HIV-infected patients who were or were not receiving a specific prophylactic treatment. The study included 386 patients with suspected PCP, 201 of whom were under specific prophylactic therapy. Induced expectoration and/or bronchoalveolar lavage provided a diagnosis of PCP in 89 patients, 21 of whom were under specific prophylaxis. Apart from a number of circulating CD4 lymphocytes that was significantly lower in the patients under prophylaxis, there was no significant difference between the two groups. Thus, being under specific prophylaxis should have no effect on the diagnosis of PCP in HIV-infected patients.
Asunto(s)
Síndrome de Inmunodeficiencia Adquirida/complicaciones , Infecciones por Pneumocystis/prevención & control , Infecciones Oportunistas Relacionadas con el SIDA/diagnóstico , Infecciones Oportunistas Relacionadas con el SIDA/prevención & control , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Infecciones por Pneumocystis/diagnóstico , Estudios ProspectivosRESUMEN
OBJECTIVES: The French drug authorities audited first-time prescription of hematopoietic growth factors using a prescription follow-up survey. Data collected between April 1995 and March 1996 were analyzed then criticized by three clinical experts working in three different areas where lenograstime is most widely used. METHODS: First-time prescription data and follow-up information were recorded on separate inclusion and follow-up diaries by the prescribing physicians. The delivering pharmacies complete the diaries and addressed them to the INSERM unit 330 for analysis. RESULTS: There were 7,102 inclusion diaries and 1376 follow-up diaries from 234 different hospital facilities. Lenograstime was most frequently prescribed in patients with lymphoma (19%), breast cancer (16.4%), and lung cancer (13.8%). Prescriptions involved 377 different chemotherapy protocols, including 196 which concerned a single patient. At the first prescription, lenograstime was given as a preventive measure in 61% of the cases and for curative therapy in 25.3%. The planned duration of preventive treatment was longer than the true period of treatment. DISCUSSION: Pr Rossi, hematologist, Pr Misset, cancerologist and Pr Lebeau, pneumologist criticized the findings.
Asunto(s)
Prescripciones de Medicamentos/estadística & datos numéricos , Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Neoplasias/terapia , Antineoplásicos/efectos adversos , Antineoplásicos/uso terapéutico , Neoplasias de la Mama/terapia , Femenino , Estudios de Seguimiento , Francia , Registros de Hospitales/estadística & datos numéricos , Humanos , Lenograstim , Neoplasias Pulmonares/terapia , Linfoma/terapia , Proteínas Recombinantes/uso terapéuticoRESUMEN
OBJECTIVE: Pretherapeutic prognostic factors for patients given chemotherapy for small cell lung carcinoma have been widely studied. We evaluated response to chemotherapy in patients included in 4 multicentric trials with less restrictive entry criteria in order to determine the contribution of clinical outcome as a predictive factor. METHODS: Pretherapeutic and therapeutic prognostic factors were assessed in 1280 patients included in 4 successive multicentric therapeutic trials on chemotherapy for small cell lung carcinoma conducted from January 1, 1983 to April 1, 1992. Logrank test for univariate analysis and Cox's stepwise method for multivariate analysis were used to evaluate the results. RESULTS: Univariate analysis identified pretherapeutic factors as significant for prognosis: Karnofsky index (p < 0.0001), alkaline phosphatase level (p < 0.0002), white cell count (p < 0.0005), age (p = 0.0007), presence of brain metastasis (p = 0.0004), presence of liver metastasis (p = 0.03), initial extension (p = 0.04). Multivariate analysis taking into account pretherapeutic and therapeutic factors demonstrated that complete response after the second and after the sixth treatment session were predictive of longer survival (p = 0.0001). This factor was more powerful than all the pretherapeutic factors including the Karnofsky index, initial extension and brain metastasis. CONCLUSION: For patients with small cell lung carcinoma, the prognostic value of early response to chemotherapy suggests that high-doses should be used starting at the first session.
Asunto(s)
Carcinoma de Células Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Células Pequeñas/mortalidad , Carcinoma de Células Pequeñas/patología , Femenino , Humanos , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Análisis Multivariante , Valor Predictivo de las Pruebas , PronósticoRESUMEN
Managed care offers many career opportunities to HIM professionals. If you're interested in making a transition to this area, the first step is understanding the ways HIM adds value to managed care processes. This article kicks off the first in a series on HIM opportunities in managed care.