RESUMEN
INTRODUCTION: Left ventricular (LV) end-systolic elastance (Ees) can be estimated using single-beat (Ees(sb)) Chen method, employing systolic and diastolic arm-cuff pressures, stroke volume (SV), ejection fraction and estimated normalized ventricular elastance at arterial end-diastole. This work aims to conduct a sensitivity analysis of Chen formula to verify its reliability and applicability in clinical scenario. METHODS: Starting from a baseline condition, we evaluated the sensitivity of Ees(sb) to the parameters contained in the formula. Moreover, a mathematical model of the cardiovascular system was used to evaluate the sensitivity of Ees(sb) to end-diastolic LV elastance (Eed), Ees, arterial systemic resistance (Ras) and heart rate (HR). RESULTS: In accordance with Ees definition, Ees(sb) increases by increasing aortic pressure and pre-ejection time, reaching the highest value for a pre-ejection time = 40 ms, and then decreases. In contrast with Ees definition, Ees(sb) increases (from 3.21 mmHg/mL to 12.15 mmHg/mL) by increasing the LV end-systolic volume and decreases by increasing the SV. In the majority of the analysis with the mathematical model, Ees was underestimated using the Chen method: by increasing Ees (from 0.5 to 2.5 mmHg/mL), Ees(sb) passes only from 0.56 to 1.54 mmHg/mL. Ees(sb) increases for higher Eed (from 1.03 to 2.33 mmHg/mL). Finally, Ees(sb) decreases (increases) for HR < 50 bpm (< 50 bpm), and for Ras < 1100 mmHg/gcm4 (> 1100 mmHg/gcm4). CONCLUSION: Unexpectedly Ees(sb) increases for higher LV end-systolic volume and decreases for higher SV. These results contrast with Ees definition, which is the ratio between the LV end-systolic pressure and the LV end-systolic volume. Moreover, Ees(sb) is influenced by cardiocirculatory parameters such as LV Eed, HR, Ras, ejection time, and pre-ejection time. Finally, Ees(sb) computed with the model output often underestimates model Ees.
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Ventrículos Cardíacos , Función Ventricular Izquierda , Reproducibilidad de los Resultados , Volumen Sistólico , Sístole , Función Ventricular Izquierda/fisiologíaRESUMEN
Despite much evidence of cognitive and affective disorders in Friedreich's ataxia (FRDA), the nature of mental status in FRDA has received little systematic attention. It has been proposed that the cerebellum may interfere indirectly with cognition through the cerebello-cortical loops, whereas the role of pathological changes in different areas of the central nervous system is still undetermined. In the present study, 13 patients with molecularly determined FRDA and a group of matched controls were evaluated by a comprehensive battery of neuropsychological tests and the Minnesota Multiphasic Personality Inventory. A repetitive task of simple visual-reaction times was used to investigate implicit learning in all subjects. Pathological changes in cortical areas were explored comparing cerebral activations of patients and controls during finger movements (functional MRI). The intelligence profile of FRDA patients is characterized by concrete thinking, poor capacity in concept formation and visuospatial reasoning. FRDA patients show reduced speed of information processing. The learning effect seen in controls was notably absent in patients with FRDA. The patients' personality is characterized by some pathological aspects and reduced defensiveness. Patterns of cortical activation during finger movements are heterogeneous in patients compared to controls. Cognitive impairment, mood disorders and motor deficits in FRDA patients may be the result of the cumulative damage caused by frataxin deficiency not only in the cerebellum and spinal cord but also in other brain areas.
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Conducta , Encéfalo/patología , Diagnóstico por Imagen/métodos , Ataxia de Friedreich/patología , Pruebas Neuropsicológicas , Adolescente , Adulto , Niño , Preescolar , Femenino , Ataxia de Friedreich/fisiopatología , Ataxia de Friedreich/psicología , Humanos , MMPI/estadística & datos numéricos , Imagen por Resonancia Magnética/métodos , Masculino , Estadísticas no Paramétricas , Tomografía Computarizada de Emisión de Fotón ÚnicoRESUMEN
Limb girdle muscular dystrophy (LGMD) type 2A (LGMD2A) is caused by mutations in the CAPN3 gene encoding for calpain-3, a muscle specific protease. While a large number of CAPN3 gene mutations have already been described in calpainopathy patients, the diagnosis has recently shifted from molecular genetics towards biochemical assay of defective protein. However, an estimate of sensitivity and specificity of protein analysis remains to be established. Thus, we first correlated protein and molecular data in our large LGMD2A patient population. By a preliminary immunoblot screening for calpain-3 protein of 548 unclassified patients with various phenotypes (LGMD, myopathy, or elevated levels of serum creatine kinase [hyperCKemia]), we selected 208 cases for CAPN3 gene mutation analysis: 69 had protein deficiency and 139 had normal expression. Mutation search was conducted using SSCP, denaturing high performance liquid chromatography (DHPLC), amplification refractory mutation system (ARMS-PCR), and direct sequencing methods. We identified 58 LGMD2A mutant patients: 46 (80%) had a variable degree of protein deficiency and 12 (20%) had normal amount of calpain-3. We calculated that the probability of having LGMD2A is very high (84%) when patients show a complete calpain-3 deficiency and progressively decreases with the amount of protein; this new data offers an important tool for genetic counseling when only protein data are available. A total of 37 different CAPN3 gene mutations were detected, 10 of which are novel. In our population, 87% of mutant alleles were concentrated in seven exons (exons 1, 4, 5, 8, 10, 11, and 21) and 61% correspond to only eight mutations, indicating the regions where future molecular analysis could be restricted. This study reports the largest collection of LGMD2A patients so far in which both protein and gene mutations were obtained to draw genotype-protein-phenotype correlations and provide insights into a critical protein domain.
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Calpaína/deficiencia , Calpaína/genética , Análisis Mutacional de ADN/métodos , Isoenzimas/deficiencia , Isoenzimas/genética , Técnicas de Diagnóstico Molecular , Proteínas Musculares/deficiencia , Proteínas Musculares/genética , Distrofias Musculares/diagnóstico , Adolescente , Adulto , Calpaína/metabolismo , Niño , Cromatografía Líquida de Alta Presión/métodos , Exones/genética , Femenino , Genotipo , Humanos , Isoenzimas/metabolismo , Pérdida de Heterocigocidad/genética , Masculino , Proteínas Musculares/metabolismo , Distrofias Musculares/genética , Mutación Missense/genética , Fenotipo , Polimorfismo Conformacional Retorcido-Simple , Desnaturalización Proteica , Sensibilidad y Especificidad , Distribución por SexoRESUMEN
Laser nephelometry is a technique which allows the evaluation of the concentration of several serum proteins and clotting factors. By means of this technique it is also possible to study the kinetics of the reaction between antigen and antibody. We studied the kinetics of the reaction between prothrombin and an antiprothrombin antiserum using several prothrombins namely: Prothrombin Padua, prothrombin Molise, which are two congenital dysprothrombinemias, cirrhotic, coumarin or normal prothrombins. Different behaviors in the kinetics of the reactions were shown even when the concentration of prothrombins was about the same in all plasma tested. These differences were analyzed by means of a computer (Apple II 48 RAM) programmed to solve four unknown equations (Rodbard's equation). From the data so obtained one can see that when voltages at the beginning and at the end of the reaction are in all cases about the same, a clear difference in the time required to reach half the maximum value of the voltage can still be demonstrated. This parameter, which is expressed in minutes, is longer in coumarin and prothrombin Molise than in controls. On the contrary it is shorter in prothrombin Padua and has about the same value of controls in the cirrhotic patient. Moreover the time at which the maximum rate is obtained is longer in coumarin and prothrombin Molise than in controls and shorter in liver cirrhosis and prothrombin Padua. In conclusion data obtained show that coumarin prothrombin behaves in a different way from cirrhotic prothrombin and also that there is a different behaviour between the two congenital dysprothrombinemias.
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Reacciones Antígeno-Anticuerpo , Protrombina/inmunología , Anticoagulantes/farmacología , Humanos , Técnicas In Vitro , Cinética , Rayos Láser , Cirrosis Hepática/sangre , Nefelometría y TurbidimetríaRESUMEN
The immunologic concentration of two abnormal antithrombins III (AT III), namely antithrombin III Padua (AT III Padua) and antithrombin III Padua2 (AT III Padua2) and the kinetics of the reaction of these two ATs III with an anti AT III antiserum was investigated by means of a laser nephelometer. The immunologic concentration of these two AT III both in presence (0.2 IU/mL) or absence of heparin was normal. On the contrary, the analysis of kinetics behavior demonstrated that AT III Padua is radically different from pooled normal plasma both in presence or in absence of heparin. This was not the case for AT III Padua2, which showed no difference from pooled normal plasma regardless of the presence or absence of heparin. Both abnormal antithrombins III reached the plateau of the reaction at about the corresponding value of pooled normal plasma, indicating a normal antigen level. These experimental data were analyzed by means of a computer (Apple II 48 RAM) programmed to solve a four unknowns equation (Rodbard's equation). This analysis showed that the time needed to reach half of the maximum voltage, i.e., the parameter C, which is expressed in minutes, is clearly longer in the case of AT III Padua samples (heparinized or not) as compared with pooled normal plasma. Moreover, the time at which the maximum rate was reached was also longer. On the contrary, in the case of AT III Padua2 there is no difference from pooled normal plasma. These data confirm the view that a different kind of defect is present in these two AT III abnormalities.(ABSTRACT TRUNCATED AT 250 WORDS)
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Antitrombina III/inmunología , Nefelometría y Turbidimetría/métodos , Reacciones Antígeno-Anticuerpo , Computadores , Heparina , Humanos , Cinética , Rayos Láser , MasculinoAsunto(s)
Antígenos/análisis , Factor X/análisis , Adulto , Cumarinas/uso terapéutico , Factor X/inmunología , Deficiencia del Factor X/sangre , Deficiencia del Factor X/genética , Femenino , Heterocigoto , Homocigoto , Humanos , Rayos Láser , Masculino , Persona de Mediana Edad , Nefelometría y Turbidimetría/métodosAsunto(s)
Alopecia Areata/sangre , Deformación Eritrocítica , Adolescente , Adulto , Niño , Femenino , Humanos , Masculino , Persona de Mediana Edad , Factores de TiempoRESUMEN
One hundred forty-five male volunteers, 60 to 91 years old, without any hepatic, renal, or metabolic pathology, and not under any steroid therapy for at least 1 year were studied. Plasma luteinizing hormone (LH), Follicle Stimulating hormone (FSH), Testosterone (T), 17-beta-Estradiol (E2), Androstenedione (A), Maximal increase (MI) of LH and FSH after luteinizing hormone releasing hormone (LHRH) (50 gamma iv), and pulsations (P) of LH and FSH over a 3 hr period were measured by radioimmunoassay (RIA). The patients were divided in four groups according to LH and T levels. Group I: (46% of our subjects) showed no signs of hypogonadism with normal LH, T, E2, A, MI of LH and FSH, and normal P-LH, P-FSH. Group II: (15%) with high LH but normal T, showed high FSH, MI-LH, MI-FSH, P-LH, and P-FSH, but normal A and E2. Group III: (22%) with classical signs of hypergonadotropic hypogonadism (high LH and low T) showed high FSH, MI-LH, MI-FSH, and P-FSH, normal P-LH and E2, but low A. Group IV: (16.5%) with signs of hypogonadotropic hypogonadism (low LH and low T) had also low MI-LH, MI-FSH and A, but normal FSH, P-LH, P-FSH, and E2. Contrarily to menopause in women, andropause is not an obligatory event in men, and when it does occur, its pathogenesis and hormonal aspects are very variable.
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Envejecimiento , Hipófisis/fisiología , Testículo/fisiología , Anciano , Androstenodiona/sangre , Estradiol/sangre , Hormona Folículo Estimulante/sangre , Hormona Liberadora de Gonadotropina , Humanos , Hormona Luteinizante/sangre , Masculino , Persona de Mediana Edad , Testosterona/sangreRESUMEN
We developed assays for the measurement of Factor VIII in a Laser Nephelometer and the results were compared with those obtained by conventional immunological methods. Marked discrepancies were obtained using different antisera and only the Dako antiserum lot 42 B yielded satisfactory results. Other antisera used (other lots of Dako antiserum, Behringwerke antiserum and Immunoscientific antiserum) failed to yield satisfactory results. From our data it seems that Laser Nephelometer has no role in the evaluation of Factor VIII complex. Statements to the contrary have to be accepted with great caution.
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Antígenos/análisis , Factor VIII/inmunología , Rayos Láser , Nefelometría y Turbidimetría/instrumentación , Reacciones Antígeno-Anticuerpo , Electroforesis de las Proteínas Sanguíneas , Factor VIII/análisis , Hemofilia A/sangre , Humanos , Inmunodifusión , Enfermedades de von Willebrand/sangre , Factor de von WillebrandRESUMEN
The bone mineral content was evaluated in 30 male subjects aged between 60 and 90 years using the relief of the percent cortical area (PCA) at the level of the second phalanx of the left-hand index finger, by Garn's method. This was to evaluate the rate of bone loss with increasing age. Testosterone, androstenedione, estrone, 17 beta-estradiol plasma levels were determined in all subjects by the RIA method. 60% of our patients showed increased bone resorption (PCA less than 55%); in these subjects testosterone and androstenedione plasma levels were significantly lower than in subjects not affected by osteoporosis. A positive linear correlation is evident between PCA and testosterone, androstenedione and estrone plasma levels. Thus, like in women, decline of gonadic function determines an increased bone resorption in men too.
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Osteoporosis/fisiopatología , Testículo/fisiopatología , Anciano , Androstenodiona/sangre , Resorción Ósea , Estradiol/sangre , Estrona/sangre , Humanos , Masculino , Persona de Mediana Edad , Osteoporosis/sangre , Testosterona/sangreRESUMEN
Factor X antigen was assayed by means of an Elisa (sandwich) method in 36 patients on long-term anticoagulant therapy. The average value observed was 31.4% +/- 12.2. In almost every instance the antigen level was higher than the clotting counterpart (14.4% +/- 4.5). In a few instances no major difference was noted between factor X antigen and factor X activity. The method correlated fairly well with other immunological methods (electroimmunoassay and Laser Nephelometer). Therefore, factor X Elisa method appears to be a suitable method for factor X antigen evaluation.
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Ensayo de Inmunoadsorción Enzimática/métodos , Factor X/análisis , Técnicas para Inmunoenzimas , Warfarina/uso terapéutico , Antígenos/análisis , Factor X/inmunología , HumanosRESUMEN
In 43 patients affected by aorto-iliac arteriopathies, gonadotropins, testosterone, androstenedione serum levels were measured to verify the presence of a testicular alteration secondary to ischemia. Important signs of testiculopathies (increased gonadotropins and decreased testosterone serum levels) were observed in patients with flow alteration of the internal spermatic artery and in patients with obstructions of the common iliac. Plasma androstenedione levels were not decreased while the A/T ratio was increased in hypotestosteronemic patients. Ischemia might determine a functional block of 17 beta reductase enzyme, necessary to convert androstenedione to testosterone. The impotentia coeundi, which affected about 50% of our patients is not related to testosteronemia.
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Aorta Torácica , Arteriopatías Oclusivas/complicaciones , Hipogonadismo/etiología , Arteria Ilíaca , Adulto , Anciano , Androstenodiona/sangre , Disfunción Eréctil/etiología , Hormona Folículo Estimulante/sangre , Humanos , Hormona Luteinizante/sangre , Masculino , Persona de Mediana Edad , Testículo/irrigación sanguínea , Testosterona/sangreRESUMEN
A family with a new factor X defect is reported. The proposita is a 56-year-old female. She is asymptomatic and no consanguinity is present between the parents. The main features of the defect are: prolongation of prothrombin time and derivative tests but normal partial thromboplastin time. Factor X was found to be low (about 25-30% of normal) only if tissue thromboplastins were used in the assay system. Chromogenic substrate S-2222 also yielded decreased factor X levels. However, factor X activity was normal with cephalin and cephalin-RVV mixture. Factor X antigen was normal in three immunological systems (electroimmunoassay, an Elisa method and laser nephelometry). Crossed immunoelectrophoresis and antigen-antibody kinetics recorded in a laser nephelometer failed to show major differences from normal factor X. Both sons of the proposita, the father and other family members showed slightly decreased factor X levels and normal factor X antigen and were considered heterozygous for the abnormality. The toponym factor X Padua is proposed to indicate this peculiar abnormality.
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Deficiencia del Factor X/genética , Hipoprotrombinemias/genética , Femenino , Heterocigoto , Homocigoto , Humanos , Persona de Mediana Edad , Tiempo de Tromboplastina Parcial , Linaje , Tiempo de ProtrombinaRESUMEN
Sex hormone binding globulin (SHBG), plasma testosterone and saliva testosterone were measured in sixty-four men with androgenetic alopecia and in forty males within the same age range without alopecia. There was a significant reduction in SHBG levels in bald men, compared with controls. Plasma testosterone levels were not raised in bald men, but their salivary testosterone levels were significantly higher than in controls.
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Alopecia/metabolismo , Saliva/análisis , Globulina de Unión a Hormona Sexual/análisis , Testosterona/análisis , Adolescente , Adulto , Alopecia/sangre , Humanos , Masculino , Testosterona/sangreRESUMEN
Twenty female patients with late onset acne and idiopathic hyperprolactinemia--but without increased levels of androgens or decreased levels of SHBG--were treated with bromocriptine. All patients had a fall of basal prolactin levels to normal and a great improvement in or even disappearance of their acne.
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Acné Vulgar/tratamiento farmacológico , Bromocriptina/uso terapéutico , Hiperprolactinemia/tratamiento farmacológico , Adolescente , Adulto , Femenino , HumanosRESUMEN
Laser Nephelometry is a technique which allows the evaluation of the concentration of several serum proteins and clotting factors. By means of this technique it is also possible to study the kinetic of the reaction between antigen and antibody. In a few instances the method was also applied in the characterization of abnormal molecules. We developed assays for the measurement of Factor IX antigen and the results were compared with those obtained by conventional immunological methods such as rocket immunoelectrophoresis. Plasmas from patients with haemophilia B, on coumarin treatment, with liver cirrhosis were studied. A standard reference curve was obtained using pooled normal plasma. The factor IX levels obtained by laser nephelometer correlated fairly well with those obtained by electroimmunoassay.
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Factor IX/análisis , Hemofilia A/sangre , Complejo Antígeno-Anticuerpo , Cumarinas/uso terapéutico , Sueros Inmunes , Cinética , Rayos Láser , Cirrosis Hepática/sangre , Nefelometría y Turbidimetría/métodos , Valores de ReferenciaRESUMEN
Another family with protein-S deficiency is described here. The defect is characterized by a reduced level of total protein-S antigen; in addition, a markedly reduced level of free protein-S antigen was found. We have studied 20 family members. Ten of them showed reduced levels of protein-S antigen. Five of the affected patients manifested 'thrombophilia'. All the symptomatic patients developed the first thrombotic event at a young age. Heparin and oral anticoagulants were useful for the treatment of the acute phase of the thrombotic events, and in 1 symptomatic patient, the life-long oral anticoagulation treatment was effective in preventing relapses. On the other hand, all the symptomatic but untreated family members developed several recurrent thrombotic episodes.