RESUMEN
The objective of this study was to determine the pharmacokinetics of single- and multi-dose ceftiofur crystalline-free acid (CCFA) administered subcutaneously at a dose of 13.2 mg/kg to 12 neonatal foals 1-3 days of age. Six foals received a single subcutaneous dose, while 6 additional foals received 4 doses of CCFA at 48-h intervals. Blood samples were collected at pre-determined times following drug administration, and plasma concentrations of ceftiofur free acid equivalents (CFAE) were measured using high-performance liquid chromatography. Following single-dose administration of CCFA, the mean ± standard deviation maximum observed plasma concentration was 3.1 ± 0.6 µg/mL and observed time to maximal plasma concentration was 14.0 ± 4.9 h. Following multi-dose administration of CCFA, the mean ±standard deviation times above CFAE concentrations of ≥0.5 µg/mL and ≥2.0 µg/mL were 192.95 ± 15.86 h and 78.80 ± 15.31 h, respectively. The mean ± standard deviation area under the concentration vs time curve (AUC0ââ ) was 246.2 ± 30.7 h × µg/mL and 172.7 ± 27.14 h × µg/mL following single- and multi-dose CCFA administrations, respectively. Subcutaneous administration of CCFA at 13.2 mg/kg in neonatal foals was clinically well- tolerated and resulted in plasma concentrations sufficient for the treatment of most bacterial pathogens associated with neonatal foal septicemia. Multi-dose administration of four doses at dosing interval of 48 h between treatments maintains appropriate therapeutic concentrations in neonatal foals.
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Antibacterianos/farmacocinética , Cefalosporinas/farmacocinética , Animales , Animales Recién Nacidos/metabolismo , Antibacterianos/administración & dosificación , Antibacterianos/sangre , Cefalosporinas/administración & dosificación , Cefalosporinas/sangre , Cromatografía Líquida de Alta Presión/veterinaria , Preparaciones de Acción Retardada , Esquema de Medicación , Femenino , Caballos/metabolismo , Inyecciones Subcutáneas/veterinaria , MasculinoRESUMEN
BACKGROUND: Nesiritide is approved in the United States for early relief of dyspnea in patients with acute heart failure. Previous meta-analyses have raised questions regarding renal toxicity and the mortality associated with this agent. METHODS: We randomly assigned 7141 patients who were hospitalized with acute heart failure to receive either nesiritide or placebo for 24 to 168 hours in addition to standard care. Coprimary end points were the change in dyspnea at 6 and 24 hours, as measured on a 7-point Likert scale, and the composite end point of rehospitalization for heart failure or death within 30 days. RESULTS: Patients randomly assigned to nesiritide, as compared with those assigned to placebo, more frequently reported markedly or moderately improved dyspnea at 6 hours (44.5% vs. 42.1%, P=0.03) and 24 hours (68.2% vs. 66.1%, P=0.007), but the prespecified level for significance (P≤0.005 for both assessments or P≤0.0025 for either) was not met. The rate of rehospitalization for heart failure or death from any cause within 30 days was 9.4% in the nesiritide group versus 10.1% in the placebo group (absolute difference, -0.7 percentage points; 95% confidence interval [CI], -2.1 to 0.7; P=0.31). There were no significant differences in rates of death from any cause at 30 days (3.6% with nesiritide vs. 4.0% with placebo; absolute difference, -0.4 percentage points; 95% CI, -1.3 to 0.5) or rates of worsening renal function, defined by more than a 25% decrease in the estimated glomerular filtration rate (31.4% vs. 29.5%; odds ratio, 1.09; 95% CI, 0.98 to 1.21; P=0.11). CONCLUSIONS: Nesiritide was not associated with an increase or a decrease in the rate of death and rehospitalization and had a small, nonsignificant effect on dyspnea when used in combination with other therapies. It was not associated with a worsening of renal function, but it was associated with an increase in rates of hypotension. On the basis of these results, nesiritide cannot be recommended for routine use in the broad population of patients with acute heart failure. (Funded by Scios; ClinicalTrials.gov number, NCT00475852.).
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Disnea/tratamiento farmacológico , Insuficiencia Cardíaca/tratamiento farmacológico , Natriuréticos/uso terapéutico , Péptido Natriurético Encefálico/uso terapéutico , Readmisión del Paciente/estadística & datos numéricos , Enfermedad Aguda , Anciano , Método Doble Ciego , Disnea/etiología , Femenino , Insuficiencia Cardíaca/complicaciones , Insuficiencia Cardíaca/mortalidad , Humanos , Hipotensión/inducido químicamente , Análisis de Intención de Tratar , Enfermedades Renales/etiología , Masculino , Persona de Mediana Edad , Natriuréticos/efectos adversos , Péptido Natriurético Encefálico/efectos adversos , RecurrenciaRESUMEN
Human herpesvirus 6B (HHV-6B) is an opportunistic pathogen associated with a growing number of complications in immunocompromised patients. Multiple reports of HHV-6B-associated hepatitis following primary HHV-6 infection and liver transplantation have appeared, but this has only been well documented in 1 patient after hematopoietic cell transplantation (HCT). This report describes a case of acute hepatitis likely caused by HHV-6B in an HCT recipient who was successfully treated with ganciclovir. HHV-6B DNA was demonstrated in plasma and hepatic tissue using quantitative polymerase chain reaction and immunohistochemical stains. Chromosomal integration was ruled out. We review the literature reporting HHV-6B-associated hepatitis, which may be an underappreciated cause of liver disease after HCT.
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Antivirales/uso terapéutico , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Hepatitis Viral Humana/virología , Herpesvirus Humano 6/fisiología , Infecciones por Roseolovirus/virología , Ganciclovir/uso terapéutico , Humanos , Masculino , Adulto JovenRESUMEN
This investigation determined the efficacy of a tart cherry juice in aiding recovery and reducing muscle damage, inflammation and oxidative stress. Twenty recreational Marathon runners assigned to either consumed cherry juice or placebo for 5 days before, the day of and for 48 h following a Marathon run. Markers of muscle damage (creatine kinase, lactate dehydrogenase, muscle soreness and isometric strength), inflammation [interleukin-6 (IL-6), C-reactive protein (CRP) and uric acid], total antioxidant status (TAS) and oxidative stress [thiobarbituric acid reactive species (TBARS) and protein carbonyls] were examined before and following the race. Isometric strength recovered significantly faster (P=0.024) in the cherry juice group. No other damage indices were significantly different. Inflammation was reduced in the cherry juice group (IL-6, P<0.001; CRP, P<0.01; uric acid, P<0.05). TAS was ~10% greater in the cherry juice than the placebo group for all post-supplementation measures (P<0.05). Protein carbonyls was not different; however, TBARS was lower in the cherry juice than the placebo at 48 h (P<0.05). The cherry juice appears to provide a viable means to aid recovery following strenuous exercise by increasing total antioxidative capacity, reducing inflammation, lipid peroxidation and so aiding in the recovery of muscle function.
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Antioxidantes/uso terapéutico , Tolerancia al Ejercicio/efectos de los fármacos , Inflamación/prevención & control , Preparaciones de Plantas/uso terapéutico , Prunus , Carrera/fisiología , Adaptación Fisiológica , Adulto , Análisis de Varianza , Antiinflamatorios/uso terapéutico , Biomarcadores , Proteína C-Reactiva , Femenino , Humanos , Inflamación/tratamiento farmacológico , Interleucina-6 , Contracción Isométrica/efectos de los fármacos , Masculino , Músculo Esquelético/efectos de los fármacos , Ácido ÚricoRESUMEN
The behavior characterizing choice response decision-making was studied in monkeys to provide background information for ongoing neurophysiological studies of the neural mechanisms underlying saccadic choice decisions. Animals were trained to associate a specific color from a set of colored visual stimuli with a specific spatial location. The visual stimuli (colored disks) appeared briefly at equal eccentricity from a central fixation position and then were masked by gray disks. The correct target association was subsequently cued by the appearance of a colored stimulus at the fixation point. The animal indicated its choice by saccading to the remembered location of the eccentric stimulus, which had matched the color of the cue. The number of alternative associations (NA) varied from 1 to 4 and remained fixed within a block of trials. After the training period, performance (percent correct responses) declined modestly as NA increased (on average 96, 93 or 84% correct for 1, 2 or 4 NA, respectively). Response latency increased logarithmically as a function of NA, thus obeying Hick's law. The spatial extent of the learned association between color and location was investigated by rotating the array of colored stimuli that had remained fixed during the learning phase to various different angles. Error rates in choice saccades increased gradually as a function of the amount of rotation. The learned association biased the direction of the saccadic response toward the quadrant associated with the cue, but saccade direction was always toward one of the actual visual stimuli. This suggests that the learned associations between stimuli and responses were not spatially exact, but instead the association between color and location was distributed with declining strength from the trained locations. These results demonstrate that the saccade system in monkeys also displays the characteristic dependence on NA in choice response latencies, while more basic features of the eye movements are invariant from those in other tasks. The findings also provide behavioral evidence that spatially distributed regions are established for the sensory-to-motor associations during training which are later utilized for choice decisions.
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Conducta de Elección , Movimientos Oculares/fisiología , Movimientos Sacádicos/fisiología , Animales , Toma de Decisiones , Macaca mulatta , Masculino , Estimulación LuminosaRESUMEN
Maternal tolerance of the fetal hemiallograft suggests that immunomodulation occurs during gestation. Therefore, recurrent spontaneous abortion (RSA) may represent a failure of the immune changes that maintain pregnancy. We hypothesized that fertile women but not women with RSA may lose their immune responses to recall antigens when pregnant. This phenomenon has been seen in immunosuppressed transplant recipients and is associated with graft survival. Therefore, we evaluated proliferative responses to recall antigens in four groups of women: group 1, nonpregnant fertile women with no history of pregnancy loss and at least one prior healthy pregnancy, n = 13; group 2, nonpregnant women with a history of three or more spontaneous abortions, n = 28; group 3, healthy pregnant women between 6 and 9 wk of gestation without a history of prior pregnancy loss, n = 15; and group 4, pregnant women between 6 and 9 wk of gestation, with a history of RSA, n = 22. Proliferative responses of peripheral blood leukocytes to the recall antigens influenza and tetanus, alloantigens, and phytohemagglutinin were determined prospectively. Positive responses (stimulation index > 3) to recall antigens (a response to either influenza or tetanus was considered positive) were as follows: group 1 (nonpregnant fertile women), 11/13 (85%); group 2 (nonpregnant RSA women), 24/28 (86%); group 3 (pregnant fertile women), 4/15 (27%) (P = 0.007); and group 4 (pregnant RSA women), 13/22 (59%) (P = 0.032) [corrected]. In group 4, there was 100% fetal survival in the nine women who lost responsiveness to recall antigens; however, in the 13/22 patients who responded to recall antigens, 9/13 (69%) had a repeat spontaneous abortion. These findings suggest that immunosuppression, indirectly measured by proliferation to recall antigens, is necessary for early pregnancy maintenance. Furthermore, this approach may be useful for predicting pregnancy outcome for women with RSA and may provide a useful means for designing and monitoring therapies.
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Aborto Habitual/inmunología , Tolerancia Inmunológica , Resultado del Embarazo , Linfocitos T Colaboradores-Inductores/inmunología , Adulto , Femenino , Humanos , Memoria Inmunológica , Activación de Linfocitos , Prueba de Cultivo Mixto de Linfocitos , Orthomyxoviridae/inmunología , Embarazo , Tétanos/inmunologíaRESUMEN
The K(+) channel mKv1.5 is thought to encode a 4-aminopyridine (4-AP)-sensitive component of the current I(K,slow) in the mouse heart. We used gene targeting to replace mKv1.5 with the 4-AP-insensitive channel rKv1.1 (SWAP mice) and directly test the role of Kv1.5 in the mouse ventricle. Kv1.5 RNA and protein were undetectable, rKv1.1 was expressed, and Kv2.1 protein was upregulated in homozygous SWAP hearts. The density of the K(+) current I(K,slow) (depolarizations to +40 mV, pA/pF) was similar in left ventricular myocytes isolated from SWAP homozygotes (17+/-1, n=27) and littermate controls (16+/-2, n=19). The densities and properties of I(peak), I(to,f), I(to,s), and I(ss) were also unchanged. In homozygous SWAP myocytes, the 50-micromol/L 4-AP-sensitive component of IK,slowwas absent (n=6), the density of the 20-mmol/L tetraethylammonium-sensitive component of I(K,slow) was increased (9+/-1 versus 5+/-1, P<0.05), and no 100- to 200-nmol/L alpha-dendrotoxin-sensitive current was found (n=8). APD(90) in SWAP myocytes was similar to controls at baseline but did not prolong in response to 30 micromol/L 4-AP. Similarly, QTc (ms) was not prolonged in anesthetized SWAP mice (64+/-2, homozygotes, n=9; 62+/-2, controls, n=9), and injection with 4-AP prolonged QTc only in controls (63+/-1, homozygotes; 72+/-2, controls; P<0.05). SWAP mice had no increase in arrhythmias during ambulatory telemetry monitoring. Thus, Kv1.5 encodes the 4-AP-sensitive component of I(K,slow) in the mouse ventricle and confers sensitivity to 4-AP-induced prolongation of APD and QTC: Compensatory upregulation of Kv2.1 may explain the phenotypic differences between SWAP mice and the previously described transgenic mice expressing a truncated dominant-negative Kv1.1 construct.
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4-Aminopiridina/farmacología , Potenciales de la Membrana/efectos de los fármacos , Canales de Potasio con Entrada de Voltaje , Canales de Potasio/fisiología , Potenciales de Acción/efectos de los fármacos , Animales , Línea Celular , Células Cultivadas , Electrocardiografía , Femenino , Expresión Génica , Marcación de Gen , Ventrículos Cardíacos/citología , Ventrículos Cardíacos/efectos de los fármacos , Canal de Potasio Kv1.5 , Masculino , Ratones , Ratones Endogámicos C57BL , Datos de Secuencia Molecular , Canales de Potasio/efectos de los fármacos , Canales de Potasio/genética , Ratas , Función VentricularRESUMEN
BACKGROUND: Cardiovascular medicine is weathering challenges on multiple fronts, and the paradigm of cardiovascular fellowship training has changed as a result. METHODS AND RESULTS: On the basis of a review of the literature and surveys of former trainees, we have evaluated our Cardiovascular Fellowship Program at the University of Iowa. We have identified principles fundamental to the training of fellows. We extend these principles to propose practical ideas for responding to the challenges we face in the rapidly changing landscape of medicine in a new millennium. CONCLUSIONS: We have proposed a few principles and numerous concrete, practical suggestions that will guide our Cardiovascular Fellowship in the future. These ideas may prove useful to other training programs.
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Cardiología/educación , Educación de Postgrado en Medicina/métodos , Selección de Profesión , Docentes Médicos , Becas , InternetRESUMEN
BACKGROUND: Myocyte hypertrophy accompanies many forms of heart disease, but its contribution to electrical remodeling is unknown. METHODS AND RESULTS: We studied mouse hearts subjected to pressure overload by surgical thoracic aortic banding. In unbanded control hearts, action potential duration (APD) was significantly longer in subendocardial myocytes compared with subepicardial myocytes. Hypertrophy-associated APD prolongation was significantly greater in subendocardial myocytes compared with subepicardial myocytes, indicating stress-induced amplification of repolarization dispersion. To investigate the underlying basis, we performed voltage-clamp recordings on dissociated myocytes. Under control unoperated conditions, subendocardial myocytes exhibited significantly less transient outward current (I(to)) than did subepicardial cells. Hypertrophy was not associated with significant changes in I(to), sustained current, or inward rectifier current densities, but peak L-type Ca(2+) current density (I(Ca,L)) increased 26% (P<0.05). Recovery from I(Ca,L) inactivation was accelerated in hypertrophied myocytes. Inhibition of calcineurin with cyclosporin A prevented increases in heart mass and myocyte size but was associated with an intermediate APD. The hypertrophy-associated increase in I(Ca,L) and the accelerated recovery from inactivation were blocked by cyclosporin A. CONCLUSIONS: These data reveal regional variation in the electrophysiological response within the left ventricle by way of a mechanism involving upregulated Ca(2+) current and calcineurin. Furthermore, these results reveal partial uncoupling of electrophysiological and structural remodeling in hypertrophy.
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Potenciales de Acción , Calcineurina/fisiología , Cardiomegalia/fisiopatología , Animales , Inhibidores de la Calcineurina , Calcio/metabolismo , Cardiomegalia/patología , Células Cultivadas , Ciclosporina/farmacología , Conductividad Eléctrica , Masculino , Ratones , Ratones Endogámicos C57BL , Miocardio/citología , Miocardio/metabolismo , Miocardio/patología , Técnicas de Placa-Clamp , Potasio/metabolismo , Presión , Función Ventricular Izquierda , Remodelación VentricularRESUMEN
BACKGROUND: Cardiac hypertrophy is considered a necessary compensatory response to sustained elevations of left ventricular (LV) wall stress. METHODS AND RESULTS: To test this, we inhibited calcineurin with cyclosporine (CsA) in the setting of surgically induced pressure overload in mice and examined in vivo parameters of ventricular volume and function using echocardiography. Normalized heart mass increased 45% by 5 weeks after thoracic aortic banding (TAB; heart weight/body weight, 8.3+/-0.9 mg/g [mean+/-SEM] versus 5. 7+/-0.1 mg/g unbanded, P<0.05). Similar increases were documented in the cell-surface area of isolated LV myocytes. In mice subjected to TAB+CsA treatment, we observed complete inhibition of hypertrophy (heart weight/body weight, 5.2+/-0.3 mg/g at 5 weeks) and myocyte surface area (endocardial and epicardial fractions). The mice tolerated abolition of hypertrophy with no signs of cardiovascular compromise, and 5-week mortality was not different from that of banded mice injected with vehicle (TAB+Veh). Despite abolition of hypertrophy by CsA (LV mass by echo, 83+/-5 mg versus 83+/-2 mg unbanded), chamber size (end-diastolic volume, 33+/-6 microL versus 37+/-1 microL unbanded), and systolic ejection performance (ejection fraction, 97+/-2% versus 97+/-1% unbanded) were normal. LV mass differed significantly in TAB+Veh animals (103+/-5 mg, P<0.05), but chamber volume (end-diastolic volume, 44+/-6 microL), ejection fraction (92+/-2%), and transstenotic pressure gradients (70+/-14 mm Hg in TAB+Veh versus 77+/-11 mm Hg in TAB+CsA) were not different. CONCLUSIONS: In this experimental setting, calcineurin blockade with CsA prevented LV hypertrophy due to pressure overload. TAB mice treated with CsA maintain normal LV size and systolic function.
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Adaptación Fisiológica , Cardiomegalia/etiología , Hipertensión/complicaciones , Hipertensión/fisiopatología , Enfermedad Aguda , Animales , Aorta Torácica , Inhibidores de la Calcineurina , Cardiomegalia/diagnóstico por imagen , Cardiomegalia/prevención & control , Ciclosporina/farmacología , Ecocardiografía , Inhibidores Enzimáticos/farmacología , Hemodinámica/efectos de los fármacos , Hipertensión/diagnóstico por imagen , Hipertensión/etiología , Ligadura , Masculino , Ratones , Ratones Endogámicos C57BLRESUMEN
The effects of large coronary vessel dilation on responses to immersion of a hand and forearm in ice water for 1 minute (that is, the cold pressor test) were calculated for 17 patients. Regional coronary blood flow and aortic and left ventricular pressures were continuously measured before and during two cold pressor tests, each performed before and after administration of sublingual (0.4 mg) or low dose intracoronary (0.01 mg) nitroglycerin. During the initial cold pressor test, heart rate and coronary pressures increased in all patients; total and regional coronary resistance usually increased in patients with severe coronary artery disease and usually decreased in patients with a normal coronary angiogram. Sublingual nitroglycerin induced important systemic effects, but intracoronary nitroglycerin did not; both induced dilation of coronary arteries viewed angiographically. Regardless of the route of nitroglycerin administration, coronary hemodynamic responses were directionally similar during the repeat cold pressor test compared with the initial one. These data support the concept that changes in tone of the large coronary arteries are not important in producing the cardiac responses observed during the cold pressor test.
Asunto(s)
Frío , Angiografía Coronaria , Circulación Coronaria , Hemodinámica , Inmersión , Nitroglicerina/farmacología , Adulto , Brazo , Presión Sanguínea , Circulación Coronaria/efectos de los fármacos , Enfermedad Coronaria/diagnóstico por imagen , Enfermedad Coronaria/fisiopatología , Vasos Coronarios/efectos de los fármacos , Frecuencia Cardíaca , Hemodinámica/efectos de los fármacos , Humanos , Masculino , Microcirculación/efectos de los fármacos , Microcirculación/fisiología , Persona de Mediana Edad , Nitroglicerina/administración & dosificación , Resistencia Vascular , VasodilataciónRESUMEN
The mechanisms responsible for the beneficial effects of calcium channel antagonists in patients with effort angina were investigated by studying the coronary hemodynamic responses of the anterior left ventricular region before and after administration of nifedipine in 13 patients whose left anterior descending coronary artery was filled by flow from collateral vessels. Nifedipine was given bucally in a dose (10 or 20 mg) that decreased aortic pressure 5 mm Hg or more. Nifedipine increased collateral flow (regional thermodilution) in only three patients (p = NS), but consistently decreased coronary resistance in the left ventricular anterior region (p less than 0.05). Anterior region myocardial oxygen consumption did not change after nifedipine administration. Lactate metabolism was evaluated in eight patients: values were abnormal in four patients before nifedipine; after nifedipine, values remained abnormal in three of these patients and became abnormal in one other. During atrial pacing stress, angina occurred in all patients before nifedipine and at the same or lower heart rate in nine patients after nifedipine. After nifedipine administered at the same rate that induced angina during the control period, collateral flow and myocardial oxygen consumption were usually lower (both p less than 0.05), but anterior region coronary resistance was unchanged compared with control values. Lactate metabolism was not usually improved. Thus, although nifedipine maintained collateral flow while aortic pressure decreased, no consistent beneficial effect on pacing-induced angina was seen.
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Arteriopatías Oclusivas/fisiopatología , Enfermedad Coronaria/fisiopatología , Hemodinámica/efectos de los fármacos , Nifedipino/farmacología , Adulto , Anciano , Angina de Pecho/fisiopatología , Arteriopatías Oclusivas/tratamiento farmacológico , Arteriopatías Oclusivas/metabolismo , Cateterismo Cardíaco , Estimulación Cardíaca Artificial , Circulación Colateral/efectos de los fármacos , Circulación Coronaria/efectos de los fármacos , Enfermedad Coronaria/tratamiento farmacológico , Enfermedad Coronaria/metabolismo , Electrocardiografía , Humanos , Lactatos/metabolismo , Ácido Láctico , Masculino , Persona de Mediana EdadRESUMEN
Fifteen patients with coronary artery spasm completed a double-blind placebo-controlled trial comparing diltiazem and nifedipine. Increasingly, higher daily doses (diltiazem, 90 to 360 mg; nifedipine, 30 to 120 mg) were administered to achieve optimal clinical effects. Daily diaries and ambulatory electrocardiographic recordings were used to assess efficacy and side effects. Both drugs significantly decreased angina frequency compared with that in the preceding placebo period (diltiazem 1.4 +/- 0.4 [mean +/- SEM] to 0.4 +/- 0.2 episodes per day; nifedipine 1.4 +/- 0.3 to 0.4 +/- 0.1 episodes per day; both p less than 0.05). Ambulatory electrocardiographic recordings showed fewer ST shifts than were expected during all treatment periods (0.02/h recorded during placebo, none during diltiazem and 0.02/h during nifedipine therapy). Although some patients responded better to one drug than the other, neither drug resulted in a clearly superior clinical response. Diltiazem was discontinued in one patient because of urticaria, but the total number of side effects was higher with nifedipine (12 of 15 patients) than with diltiazem (5 of 15, p less than 0.01). Nine patients remained symptomatic on single drug treatment and entered open label treatment with the combination of diltiazem and nifedipine. Three patients did not tolerate the combination because of important side effects; the other six also had side effects, but these were relatively minor. Four patients received no more benefit from the combination than from a single agent; the condition of two patients improved. Both diltiazem and nifedipine provide effective antianginal therapy for coronary spasm, but diltiazem has fewer side effects.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Vasoespasmo Coronario/tratamiento farmacológico , Diltiazem/uso terapéutico , Nifedipino/uso terapéutico , Adulto , Anciano , Ensayos Clínicos como Asunto , Diltiazem/administración & dosificación , Diltiazem/efectos adversos , Método Doble Ciego , Quimioterapia Combinada , Femenino , Humanos , Masculino , Persona de Mediana Edad , Nifedipino/administración & dosificación , Nifedipino/efectos adversosRESUMEN
The initial results, complications and early follow-up of 74 patients undergoing percutaneous balloon mitral valvuloplasty in seven hospitals participating in a multicenter registry are reported. Seventy-four patients with a mean age of 53 years had 75 valvuloplasty procedures performed over a 2.5 year period. Eighty-nine percent of the attempted procedures were completed and resulted in an increase in mean mitral valve area from 1.0 +/- 0.04 to 2.0 +/- 0.1 cm2 (p less than 0.0001); the valve area increased greater than or equal to 50% of the baseline valve area in 73% of the patients. Major complications included procedure-related death (2.7%), cardiac tamponade (6.7%), systemic embolism (2.7%) and emergency surgery (6.7%). At a mean follow-up period of 14.6 months, the condition of the majority of patients had improved, and 89% of 55 patients treated only with valvuloplasty were in New York Heart Association functional class I or II. Thus, hemodynamic and clinical improvement can be obtained in the majority of patients with mitral stenosis treated with balloon valvuloplasty in multiple centers. However, suboptimal results and major complications occurred in a significant number of patients and may limit this procedure to use by experienced operators in hospitals with facilities for cardiac surgery.
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Oclusión con Balón , Cateterismo/métodos , Estenosis de la Válvula Mitral/terapia , Sistema de Registros/estadística & datos numéricos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Cateterismo/efectos adversos , Femenino , Estudios de Seguimiento , Hemodinámica , Humanos , Masculino , Persona de Mediana Edad , Válvula Mitral/cirugía , Estenosis de la Válvula Mitral/fisiopatología , Estudios Multicéntricos como Asunto , Complicaciones Posoperatorias/mortalidad , Recurrencia , Rotura/etiología , Rotura/mortalidad , Tasa de SupervivenciaRESUMEN
OBJECTIVES: We sought to test the hypothesis that plasma volume (PV) expansion in heart transplant recipients (HTRs) is caused by failure to reflexively suppress the renin-angiotensin-aldosterone (RAA) axis. BACKGROUND: Extracellular fluid volume expansion occurs in clinically stable HTRs who become hypertensive. We have previously demonstrated that the RAA axis is not reflexively suppressed by a hypervolemic stimulus in HTRs. METHODS: Plasma volume and fluid regulatory hormones were measured in eight HTRs (57+/-6 years old) both before and after treatment with captopril (225 mg/day). Antihypertensive and diuretic agents were discontinued 10 days before. The HTRs were admitted to the Clinical Research Center (CRC), and, after three days of a constant diet containing 87 mEq/day of Na+, PV was measured by using the modified Evans blue dye dilution technique. After approximately four months (16+/-5 weeks), the same HTRs again discontinued all antihypertensive and diuretic agents; they were progressed to a captopril dose of 75 mg three times per day over 14 days, and the CRC protocol was repeated. RESULTS: Captopril pharmacologically suppressed (p<0.05) supine rest levels of angiotensin II (-65%) and aldosterone (-75%). The reductions in vasopressin and atrial natriuretic peptide levels after captopril did not reach statistical significance. The PV, normalized for body weight (ml/kg), was significantly reduced by 12% when the HTRs received captopril. CONCLUSIONS: Extracellular fluid volume is expanded (12%) in clinically stable HTRs who become hypertensive. Pharmacologic suppression of the RAA axis with high-dose captopril (225 mg/day) returned HTRs to a normovolemic state. These findings indicate that fluid retention is partly engendered by a failure to reflexively suppress the RAA axis when HTRs become hypervolemic.
Asunto(s)
Inhibidores de la Enzima Convertidora de Angiotensina/farmacología , Captopril/farmacología , Trasplante de Corazón/fisiología , Volumen Plasmático/efectos de los fármacos , Sistema Renina-Angiotensina/efectos de los fármacos , Estudios Cruzados , Trasplante de Corazón/efectos adversos , Hemodinámica/efectos de los fármacos , Humanos , Riñón/efectos de los fármacos , Masculino , Persona de Mediana Edad , Sistema Renina-Angiotensina/fisiología , Función Ventricular Izquierda/efectos de los fármacosRESUMEN
OBJECTIVE: To determine the relative sensitivity of cardiac A1- and A2-adenosine receptor-mediated effects to antagonism by theophylline in man. METHODS: Baseline measurements of the A-H interval (A1-adenosine receptor-mediated effect) and coronary blood flow (A2-adenosine receptor-mediated effect) were made in 10 patients with angiographically normal coronary arteries. Adenosine was then administered as a continuous intravenous infusion followed by a rapid intravenous bolus, and measurements repeated. Theophylline (5 mg/kg i.v.) was then administered, and the adenosine infusion repeated. To corroborate the results found in man, the cardiac A1- and A2-adenosine receptor-mediated effects were measured in guinea pig isolated hearts exposed to increasing concentrations of adenosine, in the absence and presence of theophylline (60 microM). RESULTS: Compared to baseline, adenosine infusion and bolus caused significant prolongation of the A-H interval (109 +/- 41 vs. 116 +/- 44 vs. 168 +/- 57 ms, respectively), and increase in coronary blood flow (46 +/- 37 vs. 86 +/- 71 vs. 172 +/- 98 ml/min, respectively). Theophylline abolished the prolongation of the A-H interval during adenosine infusion and bolus (99 +/- 36 and 107 +/- 44 ms, respectively), yet had minimal effect on the increase in coronary blood flow (63 +/- 51 and 136 +/- 121 ml/min, respectively). In guinea pig isolated hearts, theophylline was shown to significantly antagonize the A2-adenosine receptor-mediated effects only when the concentrations of adenosine were < or = 1.0 microM. CONCLUSIONS: In man, theophylline completely antagonizes the A1-adenosine receptor-mediated prolongation of the A-H interval, but has minimal effect on the A2-receptor-mediated coronary vasodilation, particularly when adenosine concentrations exceed 1.0 microM.
Asunto(s)
Adenosina/farmacología , Corazón/efectos de los fármacos , Receptores Purinérgicos/efectos de los fármacos , Teofilina/farmacología , Vasodilatadores/farmacología , Adenosina/antagonistas & inhibidores , Adulto , Anciano , Animales , Unión Competitiva , Circulación Coronaria/efectos de los fármacos , Endotelio Vascular/efectos de los fármacos , Femenino , Cobayas , Sistema de Conducción Cardíaco/efectos de los fármacos , Humanos , Masculino , Persona de Mediana Edad , PerfusiónRESUMEN
Human herpesvirus 6B (HHV-6B) frequently reactivates after cord blood transplantation (CBT). We previously reported an association between HHV-6B reactivation and delirium after hematopoietic cell transplantation. In this prospective study, 35 CBT recipients underwent twice-weekly plasma PCR testing for HHV-6 and thrice-weekly delirium assessment until day 84. There was a quantitative association between HHV-6B reactivation and delirium in univariable (odds ratio, 2.88; 95% confidence interval (CI), 0.97-8.59) and bivariable models. In addition, intensified prophylaxis with high-dose valacyclovir mitigated HHV-6B reactivation (adjusted hazard ratio, 0.39; 95% CI, 0.14-1.08). Larger trials are needed to explore the utility of HHV-6B prophylaxis after CBT.
Asunto(s)
Trasplante de Células Madre de Sangre del Cordón Umbilical/efectos adversos , Delirio/etiología , Herpesvirus Humano 6/efectos de los fármacos , Adolescente , Adulto , Niño , Estudios de Cohortes , Trasplante de Células Madre de Sangre del Cordón Umbilical/métodos , Humanos , Persona de Mediana Edad , Adulto JovenRESUMEN
The structure of a glass obtained by the melt quenching of a two-dimensional (2D) coordination network was examined. X-ray analyses disclosed a 2D-to-0D structural transformation before and after glass formation. The mechanism is unique to coordination compounds, as it is characterized by labile and flexible coordination bonds.
Asunto(s)
Vidrio/química , Cristalografía por Rayos X , Modelos Moleculares , Conformación MolecularRESUMEN
Relative evaporation and penetration of the insect repellent, N,N-diethyl-m-toluamide, has been measured by 3 methods, 2 in vivo and 1 in vitro. The evaporation rate 30 min after application was found to be similar by all 3 methods. At an applied dose of 0.25 microgram/cm2, 9.6% in vivo and 9.7% in vitro evaporated from the skin in the first hour after application. Although the techniques used produced similar results in vivo and in vitro for diethyltoluamide, studies are being conducted to further elucidate kinetics of loss by evaporation.
Asunto(s)
Benzamidas/metabolismo , DEET/metabolismo , Piel/metabolismo , Humanos , Técnicas In VitroRESUMEN
We present a case series evaluating the development and characteristics of thyroiditis following pregnancy loss. Five women were followed prospectively with measurement of thyroid function and antithyroid antibodies after pregnancy loss. Serum TSH concentrations were measured by immunoradiometric assay and antithyroid antibodies by RIA and hemagglutination techniques. All women had normal serum TSH concentrations before conception or at the time of pregnancy loss, and all but one had positive antithyroid antibodies. Pregnancy loss occurred between 5-20 weeks gestation because of ectopic pregnancy or either spontaneous or elective abortion. Two women had subclinical hypothyroidism with peak serum TSH values of 8.7 mU/L and 5.4 mU/L at 2 and 7 months after pregnancy loss, respectively. Three women had clinical hyperthyroidism with serum TSH values < or = 0.2 mU/L diagnosed between 3-11 months after pregnancy loss followed subsequently by a hypothyroid phase. Painless thyroiditis within 1 yr of pregnancy loss in these women suggests that the immunological changes of a short-term gestation may be sufficient to lead to thyroiditis.