RESUMEN
Persons living for long periods of time in malaria hyper-endemic areas may suffer from hyper-reactive malarial splenomegaly (HMS), a frequent cause of splenomegaly in such areas. Splenomegaly and sub-microscopic P. falciparum parasitaemia are hallmarks of HMS. Spleen has been suggested to play a protective antimalarial role and splenectomy may trigger symptomatic malaria attacks. Other causes of immune suppression may possibly reactivate latent malaria parasites. We report the case of an Italian 60-year-old male, who had spent 33 years in sub-Saharan Africa, who experienced a P. falciparum malaria attack 12 months after his return to Italy, concomitantly with a diagnosis of lung carcinoma possibly impairing his immune system.
Asunto(s)
Carcinoma Neuroendocrino/complicaciones , Neoplasias Pulmonares/complicaciones , Malaria Falciparum/complicaciones , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma Neuroendocrino/tratamiento farmacológico , Carcinoma Neuroendocrino/cirugía , Humanos , Huésped Inmunocomprometido , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/cirugía , Masculino , Persona de Mediana Edad , Exposición Profesional , Neumonectomía , Complicaciones Posoperatorias/parasitología , Recurrencia , TanzaníaRESUMEN
BACKGROUND: Chronic obstructive pulmonary disease (COPD) severity is usually graded upon the FEV(1) reduction and FEV(1) has been considered the most important mortality predictor with age in COPD. Recent studies suggest other factors as more powerfully related to mortality than FEV(1) in COPD patients. AIM: To assess the impact of inspiratory capacity (IC) on mortality and morbidity in COPD patients during a 5-year follow-up period. METHODS: We recruited 222 patients with mild-to-moderate COPD from January 1995 to December 2001 with an average follow-up period of 60 months (range 30-114 months). Among different respiratory parameters measured in stable conditions FEV(1), FEV(1)/FVC%, IC and PaO(2), PaCO(2) and BMI were chosen and their relationships with all-cause and respiratory mortality and with morbidity were assessed. RESULTS: All these variables were associated with mortality at the univariate analysis. However, in a multivariate regression analysis (Cox proportional hazards model) for all-cause mortality age (year), IC (%pred.) and PaO(2) (mmHg) remained the only significant, independent predictors (HR=1.056, 95%CI: 1.023-1.091; HR=0.981, 95%CI: 0.965-0.998; HR=0.948, 95%CI: 0.919-0.979, respectively). According to the same analysis, IC (%pred.) and PaO(2) (mmHg) were significant independent predictors for respiratory mortality (HR=0.967, 95%CI: 0.938-0.997; HR=0.919, 95%CI: 0.873-0.969) together with FEV(1)/FVC% and BMI (kg/m(2)) (HR=0.967, 95%CI: 0.933-1.022; HR=0.891, 95%CI: 0.807-0.985, respectively). IC (%pred.), FEV(1)/FVC%, and PaO(2) (mmHg) were also significantly related to morbidity, as independent predictors of hospital admissions because of exacerbations (OR=0.980, 95%CI: 0.974-0.992; OR=0.943, 95%CI: 0.922-0.987; OR=0.971, 95%CI: 0.954-0.996, respectively). CONCLUSION: IC (%pred.) is a powerful functional predictor of all-cause and respiratory mortality and of exacerbation-related hospital admissions in COPD patients.
Asunto(s)
Capacidad Inspiratoria , Enfermedad Pulmonar Obstructiva Crónica/mortalidad , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Anciano , Anciano de 80 o más Años , Índice de Masa Corporal , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Curva ROC , Capacidad Pulmonar Total , Capacidad VitalAsunto(s)
Carcinoma de Células Pequeñas/complicaciones , Neoplasias Pulmonares/complicaciones , Osteoartropatía Hipertrófica Secundaria/etiología , Esclerodermia Limitada/etiología , Anciano , Proteínas ELAV/análisis , Electromiografía , Humanos , Masculino , Polineuropatía Paraneoplásica/diagnóstico , Polineuropatía Paraneoplásica/etiología , SíndromeRESUMEN
Salivary gland dysfunction is a common sequela of hematopoietic progenitor cell transplantation (HPCT). The investigation of major salivary gland dysfunction with sodium pertechnetate scintigraphy is a non-invasive method that provides images of the parotid and submandibular glands. In this prospective trial, 20 HPCT patients were submitted to scintigraphic study with 99mTc-pertechenate and 67Ga in order to evaluate the major salivary glands early involvement following HPCT. Major salivary glands were evaluated prior to HCPT as well as at Days +30, +60 and +100 post transplant. Major salivary glands uptake and clearance of 99mTc-pertechenate results did not demonstrate any functional differences between pre- versus post transplant periods. Results of the 67Ga scan revealed inflammatory infiltration following HPCT, primarily in submandibular glands, suggest a persistent involvement of major salivary glands up to Day +100 after HPCT.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas/métodos , Cintigrafía/métodos , Glándulas Salivales/diagnóstico por imagen , Glándulas Salivales/lesiones , Trasplante Homólogo/métodos , Adulto , Femenino , Galio/metabolismo , Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Glándulas Salivales/metabolismo , Glándula Submandibular/metabolismo , Tecnecio/metabolismo , Trasplante Homólogo/efectos adversos , Resultado del Tratamiento , Xerostomía/etiología , Xerostomía/metabolismoRESUMEN
The purpose of this study was to evaluate reticulocyte parameters by means of flow cytometric reticulocyte counting in a group of patients who had undergone autologous and allogeneic bone marrow transplantation (BMT). The pattern of reticulocyte response and the predictive value of absolute neutrophil count (ANC), platelet count, number of CD34+ cell infused and graft source for reticulocyte response were studied. We compared absolute reticulocyte count (RetAbs), mean fluorescence index (MFI) and mean reticulocyte volume/mean corpuscular volume (MRV/MCV) ratio with conventional criteria (ANC and platelet count) in 22 allogeneic and 20 autologous BMT recipients. An abrupt increase in MRV/MCV ratio or a rise in MFI value were the earliest signs of erythropoietic recovery following allogeneic transplantation (63.6 and 22.8% of cases, respectively). In 13.6% of the cases, both parameters were observed simultaneously. All but three autologous transplant recipients showed changes in reticulocyte parameters earlier than ANC recovery. Granulocyte recovery and peripheral blood progenitor cells (PBPC) graft were predictive variables for RetAbs response in allogeneic transplant recipients. In the autologous group, predictive variables for RetAbs response were a high number of CD34+ infused cells and platelet recovery. An increase in the immature reticulocyte population is the earliest sign of haematopoietic recovery following BMT.
Asunto(s)
Trasplante de Médula Ósea/normas , Supervivencia de Injerto , Reticulocitos/citología , Adolescente , Adulto , Recuento de Células Sanguíneas , Niño , Índices de Eritrocitos , Femenino , Citometría de Flujo , Neoplasias Hematológicas/terapia , Humanos , Masculino , Persona de Mediana Edad , Probabilidad , Pronóstico , Recuento de Reticulocitos , Trasplante Autólogo , Trasplante HomólogoRESUMEN
In this open, prospective, study were enrolled 204 hospitalized elderly patients with severe (88 males, 116 females, age range 70-94). Patients were randomized to receive one of the following antibiotic treatment regimens: meropenem 500 mg i.v. t.i.d. (52); imipenem/cilastatin 500 mg i.v. t.i.d. (51), clarithromycin 500 mg + ceftriaxone 1 g i.v. b.i.d. (52), clarithromycin 500 mg + amikacin 250 mg i.v. b.i.d. (49). In 99 cases causative germs were isolated (24 meropenem, 26 imipenem, 23 clarithromycin + ceftriaxone, 26 ceftriaxone + amikacin). A satisfactory clinical, bacteriological response was achieved respectively in 86.5% 77% in meropenem; 86.3% 71% in imipenem/cilastatin; 69% 61% in ceftriaxone + clarithromycin and in 85.7% 77% in clarithromycin + amikacin. The mean total cost for each patient was $1,560; $1,620; $1,760 and $1,792 in meropenem, imipenem/cilastatin, clarithromycin + ceftriaxone and clarithromycin + amikacin respectively. This study shows that treatment with either meropenem or imipenem is as efficacious as conventional therapy in the treatment of community acquired pneumonia (CAP), and that meropenem is the most cost-effective.
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Carbapenémicos/uso terapéutico , Neumonía Bacteriana/tratamiento farmacológico , Anciano , Anciano de 80 o más Años , Antibacterianos/economía , Antibacterianos/uso terapéutico , Carbapenémicos/economía , Ceftriaxona/economía , Ceftriaxona/uso terapéutico , Cilastatina/economía , Cilastatina/uso terapéutico , Combinación Cilastatina e Imipenem , Claritromicina/economía , Claritromicina/uso terapéutico , Infecciones Comunitarias Adquiridas/tratamiento farmacológico , Infecciones Comunitarias Adquiridas/economía , Costos y Análisis de Costo/economía , Combinación de Medicamentos , Costos de los Medicamentos , Quimioterapia Combinada/economía , Quimioterapia Combinada/uso terapéutico , Femenino , Hospitalización/economía , Humanos , Imipenem/economía , Imipenem/uso terapéutico , Masculino , Meropenem , Neumonía Bacteriana/economía , Estudios Prospectivos , Tienamicinas/economía , Tienamicinas/uso terapéutico , Resultado del TratamientoRESUMEN
BACKGROUND: Carriers of the apolipoprotein A-I(Milano) (apoA-I(M)) mutant present with very low plasma HDL cholesterol and moderate hypertriglyceridemia, apparently not leading to premature coronary heart disease. The objective of this study was to establish whether this high-risk lipid/lipoprotein profile is associated with structural changes in the carotid arteries and heart, indicative of preclinical atherosclerosis. METHODS AND RESULTS: Twenty-one A-I(M) carriers were compared with age- and sex-matched control subjects from the same kindred and with 2 series of matched subjects with primary hypoalphalipoproteinemia (HA). Structural changes in the carotid arteries were defined as the intima-media thickness (IMT) measured by B-mode ultrasound. HA subjects, both recruited among patients attending our Lipid Clinic and blood donors, showed significant thickening of the carotids (average IMT, 0.86+/-0.25 and 0.88+/-0.29 mm, respectively) compared with control subjects (average IMT, 0.64+/-0.12 mm); the apoA-I(M) carriers instead showed normal arterial thickness (average IMT, 0.63+/-0.10 mm). Moreover, a significantly higher prevalence of atherosclerotic plaques was found in patients and blood donors with HA (both 57%) compared with apoA-I(M) carriers (33%) and control subjects (21%). Echocardiographic findings and maximal treadmill ECG did not differ significantly between apoA-I(M) carriers and control subjects, apart from a slight increase in left ventricular end-diastolic dimension in the carriers. CONCLUSIONS: Despite severe HA, carriers of the apoA-I(M) mutant do not show structural changes in the arteries and heart, in contrast to HA subjects, who are characterized by a marked increase in carotid IMT and increased prevalence of atherosclerotic plaques.
Asunto(s)
Apolipoproteína A-I/genética , Enfermedades de las Arterias Carótidas/diagnóstico , Heterocigoto , Hipertrigliceridemia/genética , Lipoproteínas HDL/genética , Adulto , Apolipoproteína A-I/sangre , Gasto Cardíaco/genética , Arterias Carótidas/diagnóstico por imagen , Enfermedades de las Arterias Carótidas/sangre , Colesterol/sangre , HDL-Colesterol/sangre , LDL-Colesterol/sangre , VLDL-Colesterol/sangre , Ecocardiografía , Electrocardiografía , Prueba de Esfuerzo , Femenino , Humanos , Hipertrigliceridemia/sangre , Hipertrigliceridemia/diagnóstico , Lipoproteínas HDL/sangre , Lipoproteínas HDL/deficiencia , Masculino , Triglicéridos/sangre , Túnica Íntima/diagnóstico por imagen , Túnica Media/diagnóstico por imagenRESUMEN
off aim of our study was to evaluate the effect of antihypertensive treatment on flow-mediated dilation (FMD)of a large artery, a noninvasive estimate of endothelial function, in hypertensive patients. In 78 consecutive hypertensive patients (40%men; age range, 42 to 67 years) we measured by a high-resolution ultrasound system the changes of brachial artery diameter during reactive hyperemia and after sublingual glyceryl trinitrate (400 microg); brachial artery flow velocity was measured by pulsed Doppler. The results of 2 studies are reported. In the first study, this procedure was repeated in 58 patients after 6 and 12 months of treatment with a combination of antihypertensive drugs; in a second study, the FMD was assessed in 20 patients after 2 months of monotherapy with either nifedipine or hydrochlorothiazide. In the first study, FMD was significantly increased after treatment compared with baseline (from 3.1+/-3% at baseline to 6.5+/-4.5% at 6 months and to 8.12+/-4. 6% at 12 months; P<0.001 by ANOVA), concomitant with blood pressure reduction (from 162+/-24/102+/-13 mm Hg to 141+/-12/89+/-6 mm Hg and to 141+/-9/89+/-6 mm Hg; P<0.001 by ANOVA); significant changes of endothelium-independent dilation were also observed, but only after 12 months of treatment (from 14.2+/-4.8 at baseline to 15.5+/-4.7 at 6 months and 16.8+/-5.9% at 12 months; P=0.03 by ANOVA). In the second study, FMD was significantly increased during nifedipine treatment as compared with baseline (from 5+/-6.18% at baseline to 9. 45+/-3.94%, P<0.001), while it did not change in patients receiving hydrochlorothiazide (from 5.15+/-5.28% at baseline to 4.69+/-4.34%, NS). No significant changes of endothelium-independent dilation were observed with both drugs (from 17.10+/-2.4% to 18.14+/-3.76% and from 18.73+/-4.07% to 17.46+/-4.27% during nifedipine and hydrochlorothiazide, respectively, NS). Thus, in essential hypertensive patients an improvement of the impaired FMD of the brachial artery, evaluated by noninvasive ultrasound, may be observed after long-term, effective blood pressure reduction, suggesting a beneficial effect of antihypertensive treatment on endothelial function. It seems that beyond blood pressure control, a calcium antagonist may be more effective than a diuretic in this respect.
Asunto(s)
Antihipertensivos/uso terapéutico , Presión Sanguínea , Arteria Braquial/fisiopatología , Hidroclorotiazida/uso terapéutico , Hipertensión/fisiopatología , Nifedipino/uso terapéutico , Vasodilatadores/uso terapéutico , Adulto , Anciano , Brazo/irrigación sanguínea , Presión Sanguínea/efectos de los fármacos , Monitoreo Ambulatorio de la Presión Arterial , Arteria Braquial/efectos de los fármacos , Femenino , Humanos , Hiperemia , Hipertensión/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Nitroglicerina , Flujo Sanguíneo Regional , Factores de Tiempo , Ultrasonografía DopplerRESUMEN
OBJECTIVE: The aim of this study was to evaluate the spectral analysis of the heart rate in normotensive subjects and in hypertensive patients with and without left ventricular hypertrophy (LVH), under basal conditions and after a reduction in left ventricular mass. SUBJECTS AND METHODS: In 12 normotensive subjects and 22 hypertensive patients (14 with and eight without LVH), we performed 24 h electrocardiogram Holter monitoring, ambulatory blood pressure monitoring and an echocardiographic study. Sequences of 512 R-R intervals, during daytime, afternoon and night-time periods, were taken for an evaluation of spectral analysis (Box-Jenkins method). We then calculated the absolute and percentage power spectral density of the peak centred at 0.10 Hz (low-frequency peak) and at 0.25 Hz (high-frequency peak). RESULTS: At baseline, a daytime to night-time decrease in the low-frequency peak was detected in normotensives (P < 0.01) and in hypertensives without LVH (P < 0.01), while no change was observed in hypertensives with LVH. The power spectral density low-frequency peak during the daytime and night-time was significantly greater in hypertensives with LVH than in those without LVH (P < 0.001) and in normotensive subjects (P < 0.001). Fourteen of these patients with LVH were given effective long-term antihypertensive treatment and were studied again 20 days after the treatment had been withdrawn, when blood pressure had increased to pretreatment values. In eight patients showing a reduction in LVH, we found a significant decrease in the power spectral density low-frequency peak and an increase in the high-frequency peak during daytime and night-time in respect to basal conditions, and circadian variations in the spectral indices of heart rate variability were restored. In contrast, in six patients without reversal of LVH, the power spectral density low-frequency peak did not change in respect to basal conditions and remained significantly higher in comparison with the patients with LVH regression. CONCLUSION: A reduction in LVH may be associated with restoration of daytime to night-time cardiac autonomic control, as evaluated by a power spectral analysis of the heart rate.
Asunto(s)
Electrocardiografía Ambulatoria , Frecuencia Cardíaca/fisiología , Hipertensión/fisiopatología , Hipertrofia Ventricular Izquierda/fisiopatología , Adolescente , Adulto , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Bloqueadores de los Canales de Calcio/uso terapéutico , Dihidropiridinas/uso terapéutico , Femenino , Estudios de Seguimiento , Ventrículos Cardíacos/efectos de los fármacos , Ventrículos Cardíacos/patología , Humanos , Hipertensión/tratamiento farmacológico , Hipertrofia Ventricular Izquierda/patología , Masculino , Persona de Mediana Edad , Tamaño de los Órganos/efectos de los fármacosRESUMEN
OBJECTIVE: To evaluate the interrelationships between structural alterations in the carotid arteries and left ventricular geometric patterns in a middle-aged general population. DESIGN AND METHODS: We studied 223 untreated subjects (106 females, 117 males; aged 48-64 years) living in a small town in Northern Italy (Vobarno, Brescia), using a cross-sectional design. The left ventricular mass index was assessed by echocardiography, while the intima-media thickness and the occurrence of plaque were evaluated by ultrasound. Blood pressure was determined by clinic measurements and by 24 h noninvasive ambulatory blood pressure monitoring. RESULTS: According to the presence of left ventricular hypertrophy (left ventricular mass index > 50 g/m2.7 in males and > 47 g/m2.7 in females) or concentric left ventricular remodelling (normal left ventricular mass index and relative wall thickness > 0.42), the subjects were divided into four groups: 124 subjects with normal left ventricular geometry, 73 subjects with left ventricular hypertrophy (55 with eccentric and 18 with concentric hypertrophy) and 26 subjects with concentric remodelling. The common carotid intima-media thickness and cross-sectional area were significantly greater in the subjects with concentric left ventricular hypertrophy (analysis of variance, P< 0.05) than in those with normal left ventricular geometry. A significantly higher number of plaques was observed in subjects with concentric and eccentric left ventricular hypertrophy. CONCLUSIONS: In a general population of unselected middle-aged subjects, the presence of concentric left ventricular hypertrophy was associated with an increase in intima-media thickness and with the presence of plaque in the carotid arteries, possibly contributing to the worse prognosis observed in this group of patients.
Asunto(s)
Arterias Carótidas/anatomía & histología , Ventrículos Cardíacos/anatomía & histología , Anciano , Monitoreo Ambulatorio de la Presión Arterial , Arterias Carótidas/diagnóstico por imagen , Arterias Carótidas/fisiopatología , Estudios Transversales , Electrocardiografía , Femenino , Ventrículos Cardíacos/diagnóstico por imagen , Ventrículos Cardíacos/fisiopatología , Humanos , Hipertrofia Ventricular Izquierda/diagnóstico por imagen , Hipertrofia Ventricular Izquierda/epidemiología , Hipertrofia Ventricular Izquierda/fisiopatología , Italia/epidemiología , Masculino , Persona de Mediana Edad , Ultrasonografía , Remodelación Ventricular/fisiologíaRESUMEN
The aim of this study was to evaluate the effect of the calcium antagonist Nifedipine GITS in a double-blind, randomized comparison with the diuretic hydrochlorothiazide (HCTZ) on reduction of left ventricular (LV) mass and minimal vascular resistance in a group of essential hypertensives with left ventricular hypertrophy (LVH). The effects on blood pressure and on echocardiographic LV functional parameters were also analysed. After two months of randomized treatment with Nifedipine GITS or HCTZ, if diastolic blood pressure was > 90 mmHg, a combination of the two drugs was given and was continued for 24 weeks. M-mode, 2D-guided echocardiography was used to measure LV mass index (LVMI) according to the "Penn convention". Minimal vascular resistance was measured in the forearm, from arterial pressure and maximal blood flow, using a strain gauge plethysmography. All examinations were performed before and after 8 and 24 weeks of treatment. Changes in LVMI were analysed at 8 weeks and at 24 weeks in patients receiving monotherapy ("according to protocol" analysis), and also at the end of treatment in patients taking Nifedipine or HCTZ monotherapy or the combination of the two drugs ("intention to treat" analysis). Both Nifedipine and HCTZ significantly reduced systolic and diastolic blood pressure (p < 0.001), without any significant difference between the two drug treatments. Heart rate was not significantly modified by either treatment. A progressive decrease in LVMI was observed after 8 and 24 weeks of treatment with Nifedipine monotherapy (ANOVA, p = 0.03), while the decrease in LVMI during HCTZ treatment did not progress further at 24 weeks (ANOVA, p = 0.49). A significant reduction of minimal vascular resistance was observed in patients treated with Nifedipine GITS monotherapy (ANOVA, p = 0.001), but not in the HCTZ group (ANOVA, p = 0.06). Comparison of changes of forearm minimal vascular resistance, considering baseline values, could demonstrate a greater effect during Nifedipine monotherapy as compared to HCTZ monotherapy. In conclusion, in a group of hypertensive patients with LVH, treatment for 24 weeks with Nifedipine GITS alone or in combination with HCTZ induced a significant reduction in LVMI and of forearm vascular structural changes, as evaluated by minimal vascular resistance. The decrease of minimal vascular resistance was significantly greater in patients treated with Nifedipine monotherapy, as compared to those given HCTZ.
Asunto(s)
Antihipertensivos/uso terapéutico , Bloqueadores de los Canales de Calcio/uso terapéutico , Hipertensión/tratamiento farmacológico , Hipertrofia Ventricular Izquierda/prevención & control , Miocardio/patología , Nifedipino/uso terapéutico , Adulto , Anciano , Antihipertensivos/administración & dosificación , Antihipertensivos/farmacología , Presión Sanguínea/efectos de los fármacos , Bloqueadores de los Canales de Calcio/administración & dosificación , Bloqueadores de los Canales de Calcio/farmacología , Preparaciones de Acción Retardada , Diuréticos , Método Doble Ciego , Femenino , Frecuencia Cardíaca/efectos de los fármacos , Ventrículos Cardíacos/patología , Humanos , Hidroclorotiazida/uso terapéutico , Hipertensión/complicaciones , Hipertrofia Ventricular Izquierda/etiología , Hipertrofia Ventricular Izquierda/patología , Masculino , Persona de Mediana Edad , Nifedipino/administración & dosificación , Nifedipino/farmacología , Tamaño de los Órganos/efectos de los fármacos , Inhibidores de los Simportadores del Cloruro de Sodio/uso terapéutico , Resistencia Vascular/efectos de los fármacos , Función Ventricular Izquierda/efectos de los fármacos , Remodelación VentricularRESUMEN
OBJECTIVE: We have evaluated the effects of a new calcium channel blocker, manidipine, given at both high, hypotensive and low, non-hypotensive doses, on vascular morphology, response to endothelin-1 and ICAM-1 production in mesenteric small resistance arteries of spontaneously hypertensive rats (SHR). METHODS: Ten SHR were treated with manidipine 3 mg/kg per day (high dose) and 10 with manidipine 0.3 mg/kg/per day (low dose). The drug was administered by gavage from the 4th to 12th weeks of age. Eighteen Wistar-Kyoto (WKY) rats and 18 SHR were kept untreated as controls. Rats were killed at 13 weeks. Mesenteric small arteries were dissected and mounted on a micromyograph for determination of indexes of vascular structure (media thickness, wall thickness, media/lumen ratio). RESULTS: Systolic blood pressure was significantly reduced by the high dose of the drug, while no effect was observed with low-dose manidipine. A reduction in the media/lumen ratio was observed only in SHR treated with high-dose manidipine. The response to endothelin-1 in untreated SHR was significantly lower in comparison with WKY; a significant reduction was observed in SHR treated with high-dose manidipine. ICAM-1 vascular concentrations were higher in untreated SHR than in WKY controls. Both high- and low-dose manidipine reduced ICAM-1 concentrations toward normalization. CONCLUSIONS: Manidipine at high, hypotensive, but not at low, non-hypotensive doses has been proven to reduce structural alterations in mesenteric small resistance arteries, and to normalize vascular responses to endothelin-1. In addition, manidipine, at both low and high doses, may reduce ICAM-1 vascular production, thus suggesting a possible anti-atherogenic effect.
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Antihipertensivos/farmacología , Bloqueadores de los Canales de Calcio/farmacología , Dihidropiridinas/farmacología , Endotelina-1/biosíntesis , Molécula 1 de Adhesión Intercelular/biosíntesis , Músculo Liso Vascular/metabolismo , Animales , Antihipertensivos/administración & dosificación , Arterias/efectos de los fármacos , Arterias/metabolismo , Presión Sanguínea/efectos de los fármacos , Peso Corporal/efectos de los fármacos , Bloqueadores de los Canales de Calcio/administración & dosificación , Dihidropiridinas/administración & dosificación , Masculino , Músculo Liso Vascular/anatomía & histología , Músculo Liso Vascular/efectos de los fármacos , Nitrobencenos , Piperazinas , Ratas , Ratas Endogámicas SHR , Ratas Endogámicas WKY , Resistencia Vascular/efectos de los fármacos , Resistencia Vascular/fisiologíaRESUMEN
The aim of this study was to evaluate the delayed effects of an angiotensin converting enzyme (ACE) inhibitor on blood pressure and on structural and functional alterations in mesenteric small resistance arteries of spontaneously hypertensive rats (SHR). The ACE inhibitor fosinopril (25 mg/kg/day) was administered according to three different schedules: in one group of SHR from 4 to 8 weeks of age (n = 12), in a second group from 8 to 12 weeks of age (n = 15), and in a third group from 4 to 12 weeks of age (n = 12). Eighteen untreated SHR and 18 untreated Wistar-Kyoto rats served as controls. About half the animals in each group were killed at 13 weeks of age, and the remaining were killed at 38 weeks of age. After death, relative left ventricular mass (left ventricular weight/body weight) was calculated. Vascular morphology (media:lumen ratio) and function (responses to norepinephrine and acetylcholine) in mesenteric small resistance arteries were then assessed using a micromyographic technique. Short-term fosinopril, given either before or after the development of hypertension, persistently reduced (but did not normalize) systolic blood pressure, vascular structural alterations, and reactivity to norepinephrine in mesenteric resistance arteries in SHR. These favorable effects were maintained at least for 26 to 30 weeks after treatment withdrawal. The endothelium-dependent vasodilator response to acetylcholine was improved at 13 but not at 38 weeks of age, in treated SHR. Therefore, the vascular response to norepinephrine seems to be dependent mainly on the structure of the vessels, whereas endothelial function is probably more linked to the hemodynamic load.
Asunto(s)
Inhibidores de la Enzima Convertidora de Angiotensina/farmacología , Fosinopril/farmacología , Arterias Mesentéricas/efectos de los fármacos , Animales , Presión Sanguínea/efectos de los fármacos , Endotelio Vascular/efectos de los fármacos , Endotelio Vascular/fisiología , Corazón/anatomía & histología , Corazón/efectos de los fármacos , Masculino , Arterias Mesentéricas/anatomía & histología , Arterias Mesentéricas/fisiología , Norepinefrina/farmacología , Tamaño de los Órganos/efectos de los fármacos , Ratas , Ratas Endogámicas SHR , Ratas Endogámicas WKY , Factores de Tiempo , Resistencia Vascular/fisiología , Vasoconstrictores/farmacologíaRESUMEN
OBJECTIVE: To evaluate the effects of long-term antihypertensive therapy with the angiotensin converting enzyme inhibitor lisinopril on structural alterations and the endothelial function of small resistance arteries in hypertensive patients with left ventricular hypertrophy. METHODS: Fourteen patients with left ventricular hypertrophy were treated for 3 years with a lisinopril-based regimen. Patients underwent an echocardiographic evaluation of left ventricular mass index at baseline, during the first and third years of treatment. At the end of the treatment period, subcutaneous small resistance arteries (obtained by biopsy of the subcutaneous fat from the gluteal region) were dissected and mounted on a micromyograph (Mulvany's technique); the media : lumen ratio was then calculated. Data obtained were compared with those observed for 14 untreated essential hypertensive patients and 14 normotensive subjects, age- and sex-matched. RESULTS: In the present study, a significantly lower media : lumen ratio was observed in treated compared with untreated hypertensive patients, although it remained significantly higher than that in normotensive subjects. In treated hypertensive patients a significant reduction in clinic blood pressure was observed. However, their blood pressure remained significantly higher than that in normotensive subjects. Significant correlations between the media : lumen ratio and blood pressure, left ventricular mass index or changes in left ventricular mass index during treatment were observed. The response to acetylcholine administration was reduced in untreated hypertensives compared with that in normotensives. In patients treated with lisinopril, the vasodilatation obtained with the two higher doses of acetylcholine was greater than that in untreated hypertensives, thus suggesting an improvement of endothelial function. CONCLUSIONS: Long-term therapy based on lisinopril was associated with a smaller media : lumen ratio in the subcutaneous small resistance arteries of hypertensive patients with left ventricular hypertrophy. Our retrospective study confirms previous findings obtained in prospective studies with other angiotensin converting enzyme inhibitors. Endothelial function was probably improved by lisinopril therapy.
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Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Arterias/efectos de los fármacos , Hipertensión/tratamiento farmacológico , Hipertrofia Ventricular Izquierda/tratamiento farmacológico , Lisinopril/uso terapéutico , Anciano , Arterias/patología , Arterias/fisiopatología , Endotelio Vascular/efectos de los fármacos , Endotelio Vascular/fisiología , Femenino , Humanos , Hipertensión/patología , Hipertensión/fisiopatología , Hipertrofia Ventricular Izquierda/fisiopatología , Masculino , Persona de Mediana EdadRESUMEN
The angiotensin II type 1 (AT1) receptor has a key role in mediating the vasoconstrictor and growth-promoting effects of angiotensin II. It has been reported that a polymorphism of the AT1 receptor gene (an A/C transversion at position 1166) may be associated with cardiovascular phenotypes, such as arterial blood pressure and aortic stiffness, that underlie a condition of increased cardiovascular risk. We examined a sample of 212 subjects randomly selected from a general population in northern Italy to investigate the role of AT1 receptor gene polymorphism, in the regulation of blood pressure and cardiovascular growth. We measured blood pressure (both clinic and 24-hour ambulatory recording), left ventricular mass (echocardiography), and carotid artery wall thickness (B-mode ultrasound); we assessed the AT1 receptor genotype by polymerase chain reaction and allele-specific oligonucleotide hybridization. Blood pressure values were lower in CC homozygotes than in heterozygotes and AA homozygotes; the difference was statistically significant for clinic measurements (mean difference for mean blood pressure, -6.6 mm Hg, P = .01; 95% confidence interval, -1.6 to -11.7 mm Hg) but not for ambulatory blood pressure measurements. CC homozygotes also presented a lower incidence of a positive family history of hypertension (P = .027). No statistically significant differences among AT1 receptor A/C1166 genotypes were observed for left ventricular mass or carotid artery wall thickness. We conclude that the present study does not support a major role of the AT1 receptor gene A/C1166 polymorphism as a marker of conditions associated with increased cardiovascular risk.
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Presión Sanguínea/genética , Receptores de Angiotensina/genética , Enfermedades Cardiovasculares/genética , Arterias Carótidas/patología , Femenino , Genética de Población , Humanos , Italia , Masculino , Persona de Mediana Edad , Fenotipo , Polimorfismo Genético , Distribución Aleatoria , Receptor de Angiotensina Tipo 1 , Factores de RiesgoRESUMEN
The aim of our study was to evaluate whether initial changes of cardiovascular structure and/or function can be detected in young normotensive subjects with (F+) and without (F-) family history of hypertension. Thirty-two subjects (19 F+, 10 males and 9 females, age range 17-32 years; 13 F-, 6 males and 7 females, age range 19-33 years) were studied. In each subject 24 hours ambulatory blood pressure monitoring, a M-mode, 2d guided and pulsed doppler echocardiogram and postischemic forearm strain gauge plethysmography were performed. The two groups of subjects did not differ for causal systolic and diastolic BP and 24 hours systolic and diastolic ambulatory monitored blood pressure. No differences in LV end-diastolic and end-systolic diameters, as well as in LV wall thickness, and in LV mass index were observed. Systolic functional parameters were also similar in the two groups. In F+ subjects peak early filling velocity was reduced in respect to F- (p < 0.01), peak late filling velocity integral was increased (p < 0.05) and the ratio of peak E/peak A integrals was decreased (p < 0.05). No difference was observed for postischemic forearm blood flow and minimal vascular resistance, taken as an index of arteriolar structural changes as well as intima-media thickness of carotid arteries. In conclusion in this study F+ and F- had similar BP values, LV mass and min VR; differences previously observed in LV mass between F+ and F- may have been due to the presence of different basal levels of BP; in F+ LV diastolic filling, although still in the normal range, shifted early toward the pattern of LV filling usually observed in hypertensive patients.
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Sistema Cardiovascular/fisiopatología , Hipertensión/fisiopatología , Adulto , Presión Sanguínea , Monitoreo Ambulatorio de la Presión Arterial , Femenino , Humanos , Hipertensión/genética , Hipertrofia Ventricular Izquierda , Masculino , Resistencia Vascular , Función Ventricular IzquierdaRESUMEN
The aims of this study were to determine the prevalence of structural changes in the carotid arteries and heart and the correlation between these changes and the commonly recognized cardiovascular risk factors in the general population. Structural changes in the carotid arteries were defined as the intima-media thickness of the artery measured by B-mode ultrasound. Changes in the heart were defined as left ventricular mass index (LVMI) measured by echocardiography. LVMI values greater than 134 g/m2 in men and greater than 110 g/m2 in women were considered abnormal, indicating the presence of left ventricular hypertrophy. Blood pressure (BP) was measured in the clinic setting with a mercury sphygmomanometer and by 24-hour noninvasive ambulatory monitoring. Hypertension was defined as a sustained systolic BP greater than or equal to 160 mm Hg and/or diastolic BP increase greater than or equal to 95 mm Hg. The study population consisted of 225 subjects (107 women and 118 men) 48 to 64 years old. Prevalence of intima-media thickening (intima-media thickness > 1 mm) was 11% in normotensive subjects and 44% in hypertensive subjects. The presence of plaque (wall thickening with either mineralization or focal protrusion in the lumen at least 50% greater than the surrounding wall, usually > 2 mm) was observed in 35% of normotensive subjects and 44% of hypertensive subjects. The prevalence of left ventricular hypertrophy was 13% in normotensive subjects and 19% in hypertensive subjects. Intima-media thickness in the common and bifurcation segments of carotid arteries correlated well with LVMI (r = .20 and r = .19, respectively; P < .01). Intima-media thickness and LVMI were both positively related to 24-hour monitored BP (P < .01). However, in the multivariate analysis, body mass index (P = .027), sex (P < .001), and 24-hour mean BP (P = .025) were the most significant determinants of LVMI, whereas carotid artery intima-media thickness was found to be associated best with age (P < .001), cigarette smoking (P = .009), serum cholesterol (P = .025), serum glucose (P = .038), and nighttime systolic BP (P = .006). Logistic regression analysis confirmed the association between the presence of plaque and age (P < .001), nighttime systolic BP (P < .05), and cigarette smoking (P < .05); a negative association between plaque and the decrease in mean systolic BP daytime to nighttime was also observed (P < .001). In conclusion, in a general population of unselected middle-aged subjects, carotid wall thickness and LVMI were associated with each other and related to 24-hour BP levels although the major determinants of carotid wall and cardiac structure were different.
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Monitoreo Ambulatorio de la Presión Arterial , Presión Sanguínea , Sistema Cardiovascular/diagnóstico por imagen , Anciano , Arterias Carótidas/diagnóstico por imagen , Enfermedades de las Arterias Carótidas/diagnóstico por imagen , Vasos Coronarios/diagnóstico por imagen , Estudios Transversales , Ecocardiografía , Femenino , Humanos , Arteriosclerosis Intracraneal/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Túnica Íntima/diagnóstico por imagen , Túnica Media/diagnóstico por imagenRESUMEN
OBJECTIVE: To examine the cardiovascular effects of acute systemic nitric oxide synthesis inhibition in humans in relation to the possible involvement of changes in sympathetic nervous system activity or in the baroreceptor reflex. DESIGN: Placebo or NG-monomethyl-L-arginine (250 mg by intravenous infusion for 5 min) was administered to seven healthy male volunteers according to a random, double-blind sequence. METHODS: Blood pressure and heart rate were measured non-invasively using a Finapres device from 20 min before to 80 min after starting infusion; beat-to-beat variability of blood pressure, pulse interval and systolic blood pressure and pulse interval covariation were assessed by means of spectral and sequence analysis methods. Under basal conditions and 15 min and 60 min after infusion, we measured stroke volume and indices of cardiac systolic and diastolic function by echocardiography, forearm blood flow by strain-gauge venous occlusion plethysmography, and plasma catecholamine levels. RESULTS: Compared with placebo, administration of NG-monomethyl-L-arginine caused a transient increase in blood pressure and reduction in heart rate. Stroke volume and indices of cardiac function did not change significantly, whereas cardiac index and forearm blood flow were significantly reduced after 15 min. Spectral analysis of blood pressure and pulse interval showed a significant reduction of power spectral density in the low frequencies (0.03-0.15 Hz) that persisted 60 min after infusion. The plasma noradrenaline level was significantly reduced after 15 min. No change in baroreflex engagement or sensitivity was detected by the cross-spectral or the sequence method. CONCLUSIONS: Acute systemic nitric oxide synthesis inhibition transiently increases blood pressure and reduces heart rate and cardiac index. The acute hypertensive response to NG-monomethyl-L-arginine is dependent neither on sympathetic nervous system activity, which is probably reduced as a consequence of baroreceptor reflex activation, nor on baroreceptor reflex sensitivity, which is not impaired.
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Barorreflejo/fisiología , Sistema Cardiovascular/inervación , Hemodinámica/fisiología , Óxido Nítrico/biosíntesis , Sistema Nervioso Simpático/fisiología , Adulto , Arginina/análogos & derivados , Arginina/farmacología , Fenómenos Fisiológicos Cardiovasculares , Sistema Cardiovascular/metabolismo , Catecolaminas/sangre , Ecocardiografía , Inhibidores Enzimáticos/farmacología , Humanos , Masculino , Óxido Nítrico/antagonistas & inhibidores , Sistema Nervioso Simpático/metabolismo , omega-N-MetilargininaRESUMEN
BACKGROUND: For the evaluation in humans of structural alterations in resistance arteries, most studies have used an indirect index, the measurement of minimal vascular resistance (mean blood pressure divided by maximal postischaemic blood flow) in suitable vascular beds. A sensitive and specific micromyographic technique was recently made available for the study of human small resistance arteries. Whether a correlation really exists between results obtained with the two techniques has not yet been investigated. OBJECTIVE: To evaluate both forearm minimal vascular resistance and media:lumen ratio of omental or subcutaneous small arteries in normotensive subjects and hypertensive patients. DESIGN AND METHODS: Thirty-four individuals were included in the study (age range 35-74 years; 24 hypertensive, 10 normotensive). Twenty-five had elective abdominal surgery and nine hypertensive patients had a gluteal biopsy. Omental and subcutaneous small arteries were dissected and mounted on a wire micromyograph (Mulvany's technique), and media:lumen ratio and media thickness were measured. The dose-response curve to noradrenaline was constructed at cumulative concentrations from 3 x 10(-9) to 3 x 10(-5) mol/l. Venous occlusion plethysmography was used to measure blood flow in the forearm, and minimal vascular resistance was calculated from mean blood pressure and postischaemic maximal blood flow (13 min ischaemia plus exercise). RESULTS: A statistically significant correlation was found between media:lumen ratio and minimal vascular resistance (r = 0.74, P < 0.001) as well as between media:lumen ratio and systolic (r = 0.44, P < 0.01) and diastolic (r = 0.38, P < 0.05) blood pressures. Similar correlations were observed between media thickness and systolic and diastolic blood pressures. Small arteries from hypertensive patients had a significantly increased reactivity to noradrenaline (by analysis of variance) compared with those from normotensive subjects, in terms of wall tension but not of active media stress. CONCLUSIONS: The present study demonstrated that the media:lumen ratio of small resistance vessels is significantly related to forearm minimal vascular resistance, suggesting that direct and indirect evaluations of vascular morphology will give similar results.
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Arterias/fisiopatología , Hipertensión/fisiopatología , Túnica Media/patología , Resistencia Vascular , Adulto , Anciano , Arterias/patología , Femenino , Antebrazo/irrigación sanguínea , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Regression of cardiovascular structural changes is a main goal of antihypertensive treatment. Two recent meta-analyses of relatively small noncomparative studies have suggested that angiotensin-converting enzyme (ACE) inhibitors may be more effective than other classes of drugs in inducing regression of left ventricular hypertrophy (LVH). The effect of different antihypertensive drugs on arteriolar structural changes has not yet been properly investigated. The aim of this study was to evaluate the effect of 6 months of treatment with amlodipine (5-10 mg o.d.) or enalapril (10-20 mg o.d.) on blood pressure (BP) (ambulatory monitoring), heart rate (HR), LV mass and function (M-mode echo, two-dimensionally guided), forearm minimal vascular resistance (min VR = BP/max blood flow-venous occlusion plethysmography, taken as an index of vascular structural changes) in 24 hypertensive patients in a comparative single-blind, randomized study, with blind reading of echocardiograms and plethysmographic tracings. After 6 months of treatment with amlodipine 5-10 mg o.d., significant reductions in LV mass index (p = 0.004) and forearm min VR (p = 0.02) were observed. Before and during treatment, LV systolic function, both at rest and during stress (handgrip test), evaluated by fractional shortening as related to end-systolic stress, was in every case within 95% confidence limits calculated in normal subjects. Similar results were observed with enalapril. No significant differences were observed for Doppler indices of diastolic filling after 6 months of treatment with either drug. These results indicate that a significant regression of structural changes in the heart and in the small resistance vessels can be observed after long-term treatment with amlodipine in essential hypertensive patients.(ABSTRACT TRUNCATED AT 250 WORDS)