RESUMEN
PURPOSE: To compare, in a double-blind, placebo-controlled, randomized trial, the efficacy of two different doses of the depot formulation of adrenocorticotropic hormone (ACTH) in controlling delayed emesis after cisplatin. PATIENTS AND METHODS: One hundred fifty-two patients were enrolled onto the study. On day 1, all patients received cisplatin (60 to 120 mg/m2) and a combination of dexamethasone 20 mg plus ondansetron or metoclopramide to prevent acute emesis. On day 2 (24 hours after cisplatin administration), patients were randomized to receive placebo, or ACTH 1 mg intramuscularly (I.M.), or ACTH 2 mg I.M. plus one additional dose of 1 mg on day 4. Details of vomiting, nausea, and adverse effects were recorded daily for every 24-hour period from day 2 to day 6. In a subset of patients, serum cortisol levels were measured between 20 and 72 hours after cisplatin administration. RESULTS: One hundred fifty patients were assessable. Over the 5 days of the study, delayed vomiting occurred less frequently in the patients treated with ACTH 2 mg plus 1 mg than in those treated with ACTH 1 mg or placebo (28%, 38%, and 65%, respectively; P = .001). The greatest observed differences were seen on days 2 (24 to 48 hours; P = .01) and 3 (48 to 72 hours; P = .01). On days 4, 5, and 6 (96 to 144 hours), no significant differences were observed among the three arms. The severity of delayed emesis expressed as the mean number of emetic episodes per day was 0.48, 0.70, and 0.80, respectively (P = .002). Patients treated with the higher dose of ACTH had the least nausea on day 3 (P = .02) and day 4 (P = .03). Adrenal cortisol secretion rapidly increased after ACTH injection, but was suppressed for approximately 44 hours in the placebo group. Toxicity was mild and transient in all groups. CONCLUSION: ACTH reduces the incidence and severity of delayed vomiting and nausea after cisplatin. A dose of 2 mg 24 hours after cisplatin is better than one of 1 mg. Whether the activity of ACTH is mediated only by adrenal corticosteroids needs to be verified.
Asunto(s)
Hormona Adrenocorticotrópica/administración & dosificación , Antineoplásicos/efectos adversos , Cisplatino/efectos adversos , Neoplasias/tratamiento farmacológico , Vómitos/prevención & control , Adulto , Anciano , Antieméticos/uso terapéutico , Preparaciones de Acción Retardada , Dexametasona/uso terapéutico , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Esquema de Medicación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Vómitos/inducido químicamenteRESUMEN
In a prospective study, 144 white nuns belonging to a secluded monastic order and 138 white control laywomen were followed for 20 years to investigate whether living for a long time in a stress-free environment influences the effect of aging on blood pressure. Silence, meditation, and isolation from society are the distinctive features of the life-style examined. At study entry, blood pressure was not dissimilar in the nuns and the control group, but it increased over time only in the controls, with a mean slope of the regression line (beta coefficient) of 0.089 in the nuns (NS) and 2.171 in the controls (p less than 0.0001) for systolic blood pressure and of 0.054 in the nuns (NS) and 0.742 in the controls (p less than 0.0001) for diastolic blood pressure. Weight and body mass index increased similarly over time in the two groups. Family history of hypertension was not dissimilar between the groups. Serum cholesterol and triglycerides, higher at study entry in the nuns, increased similarly over time in the two groups. Twenty-four-hour urinary sodium excretion, collected randomly in both groups, did not differ over time between nuns and controls. None of the women smoked or used oral contraceptives. Educational level was higher in the control group, but subgroups of 48 nuns and 52 laywomen of comparable educational level maintained the same difference in the blood pressure trend over time as in the main cohort. Parity affected the increase of systolic, but not of diastolic, blood pressure with age among the laywomen, but nuns and no-childbirth controls maintained a significantly different blood pressure trend over time.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Envejecimiento , Presión Sanguínea , Adulto , Dieta , Femenino , Estudios de Seguimiento , Humanos , Estilo de Vida , Persona de Mediana Edad , Embarazo , Religión , Estrés Psicológico/fisiopatologíaRESUMEN
Aromatase inhibitors are known to be effective in the treatment of advanced postmenopausal breast cancer. To assess the efficacy of the aromatase inhibitor 4-hydroxyandrostenedione (4-OHA) as first-line treatment in patients who were either resistant to or had relapsed after adjuvant therapy, 50 eligible patients received intramuscular 4-OHA either 250 mg or 500 mg fortnightly until disease progression or severe adverse events. Of the 43 patients evaluable for clinical response (UICC criteria), 15 (36%) showed objective response (CR+PR), 6 (14%) stable disease (SD). In relation to disease site, objective responses were obtained in 55% of cases with soft tissue metastases (16/29); in 33% with visceral metastases (8/24), and in 24% with bone involvement (5/21). In relation to previous adjuvant treatment, there were eight objective responses among the 17 patients treated with chemotherapy (47%), and seven objective responses among the 24 treated with tamoxifen (29%). The treatment was well tolerated. These results support the hypothesis that adjuvant therapy, whether hormonal or chemotherapy, may make patients less responsive to subsequent treatment.
Asunto(s)
Androstenodiona/análogos & derivados , Inhibidores de la Aromatasa , Neoplasias de la Mama/tratamiento farmacológico , Menopausia , Anciano , Androstenodiona/efectos adversos , Androstenodiona/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Quimioterapia Adyuvante , Ciclofosfamida/administración & dosificación , Doxorrubicina/administración & dosificación , Femenino , Fluorouracilo/administración & dosificación , Humanos , Metotrexato/administración & dosificación , Persona de Mediana Edad , Inducción de Remisión , Tamoxifeno/uso terapéutico , Resultado del TratamientoRESUMEN
The choice of treatment for elderly breast cancer patients needs particular care because the presence of physiological functional impairments can modify the drug bioavailability in an unpredictable manner. Hormonal treatment remains one of the choices and, although tamoxifen has proved to be effective in any setting, the use of selective aromatase inhibitors is arousing. Depending on their chemical structure, aromatase inhibitors are either steroidal (such as exemestane and formestane) or non-steroidal (such as letrozole, vorozole and anastrozole). Formestane has been studied in elderly patients with breast cancer and has been found to induce an overall response rate of 51% (95% CI, 35-67%). The drug suppresses estradiol (E2) levels, and changes in other hormones (FSH, LH and SHBG) are observed, but with poor clinical significance, thus confirming its selectivity and potency. Formestane has also been demonstrated to be as effective as tamoxifen. Exemestane and non-steroidal aromatase inhibitors appear to be very promising drugs.
Asunto(s)
Inhibidores de la Aromatasa , Neoplasias de la Mama/tratamiento farmacológico , Inhibidores Enzimáticos/uso terapéutico , Anciano , Anastrozol , Androstadienos/administración & dosificación , Androstadienos/efectos adversos , Androstadienos/uso terapéutico , Androstenodiona/administración & dosificación , Androstenodiona/efectos adversos , Androstenodiona/análogos & derivados , Androstenodiona/uso terapéutico , Antineoplásicos/administración & dosificación , Antineoplásicos/efectos adversos , Antineoplásicos/uso terapéutico , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/fisiopatología , Inhibidores Enzimáticos/administración & dosificación , Inhibidores Enzimáticos/efectos adversos , Femenino , Humanos , Letrozol , Nitrilos/administración & dosificación , Nitrilos/efectos adversos , Nitrilos/uso terapéutico , Triazoles/administración & dosificación , Triazoles/efectos adversos , Triazoles/uso terapéuticoRESUMEN
Letrozole is an orally competitive aromatase inhibitor. This double-blind, randomised, multicentre trial was carried out to evaluate the endocrine effects of two doses of letrozole, 0.5 mg versus 2.5 mg orally daily, in postmenopausal advanced breast cancer patients progressing after tamoxifen. The pharmacokinetics of letrozole was also assessed. 46 patients entered the trial, 22 on letrozole 0.5 mg and 24 on 2.5 mg. A significant suppression of oestrone and oestradiol levels was achieved by both letrozole doses. Neither letrozole dose induced any changes in cortisol and aldosterone production at rest or after Synacthen stimulation. Androstenedione, testosterone, 17 alpha-OH progesterone, triiodothyronine (T3) thyroxine, (T4) and thyroid-stimulating hormone (TSH) plasma levels did not show any significant changes. Sex hormone binding globulin (SHBG), follicle-stimulating hormone (FSH) and luteinising hormone (LH) levels increased significantly over time. Plasma letrozole concentrations increased until reaching steady-state values after 1 month at the dose of 0.5 mg and after 2 months at 2.5 mg. In conclusion, both letrozole doses suppressed oestrogen levels without affecting adrenal activity.
Asunto(s)
Inhibidores de la Aromatasa , Neoplasias de la Mama/tratamiento farmacológico , Nitrilos/administración & dosificación , Triazoles/administración & dosificación , Adulto , Anciano , Anciano de 80 o más Años , Aromatasa/administración & dosificación , Aromatasa/efectos adversos , Aromatasa/farmacocinética , Neoplasias de la Mama/metabolismo , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Femenino , Humanos , Letrozol , Persona de Mediana Edad , Nitrilos/efectos adversos , Nitrilos/farmacocinética , Posmenopausia , Triazoles/efectos adversos , Triazoles/farmacocinéticaRESUMEN
The aim of our study is to evaluate insulin-like growth factor (IGF) and IGF binding protein (IGFBP)-3 circulating levels in postmenopausal women treated with type I aromatase inhibitor formestane for breast cancer. Sixty-three patients at their first relapse entered the trial and were randomly given formestane at 250 mg or 500 mg i.m. fortnightly. Effects of the endocrine treatment on IGF-1 and IGFBP-3 were measured before and during therapy at scheduled times. IGF-1 and IGFBP-3 seems to slightly increase in both the dose groups, but only IGFBP-3 levels showed statistically significant fluctuation (baseline vs 4 weeks, p=0.01925; baseline vs 10 weeks, p=0.04537). These modifications are unlikely to be related to clinical status because they were observed both in responsive and unresponsive patients. This report demonstrates that hormonal treatments for breast cancer (particularly, aromatase inhibitor administration) can modify growth factor disposition to tumour.
RESUMEN
Formestane, a new selective aromatase inhibitor devoid of severe side-effects, has been shown to be active in patients with advanced breast cancer. To investigate the clinical activity and endocrinological effects of formestane as a first-line treatment, 52 patients were administered two different doses: 24 received 250 mg formestane and 28 received 500 mg formestane i.m. fortnightly. All of the patients had a performance status of 2 or less (ECOG scale), 34 (65%) had a disease-free interval of at least 2 years and 21 (40%) were both oestrogen-receptor- and progesterone-receptor-positive; 20 patients received hormone and 13, received chemotherapeutical adjuvant treatment. Objective responses were obtained in 8 patients in the 250-mg group (33%; 95% CI: 14%-52%) and in 13 patients in the 500-mg group (46%; 95% CI: 28%-64%). The median response duration in the two groups was respectively 11 and 12 months. E2 serum levels of oestradiol had significantly (P < 0.001) decreased to more than 40% below the baseline value in both groups after 15 days of treatment, and remained unchanged thereafter. Local and systemic tolerability was satisfactory. We conclude that formestane is an effective and well-tolerated agent in previously untreated patients, and that these results should be confirmed by further studies.
Asunto(s)
Androstenodiona/análogos & derivados , Antineoplásicos/uso terapéutico , Inhibidores de la Aromatasa , Neoplasias de la Mama/tratamiento farmacológico , 17-Hidroxicorticoesteroides/orina , Anciano , Androstenodiona/administración & dosificación , Androstenodiona/uso terapéutico , Antineoplásicos/administración & dosificación , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Esquema de Medicación , Estradiol/sangre , Femenino , Humanos , Inyecciones Intramusculares , Persona de Mediana Edad , Posmenopausia , Pronóstico , Factores de Riesgo , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
To extend our previous findings that a low-Na/high-K salt (S) reduces BP in hospitalized patients, a multicenter study was performed. After a placebo period during which patients were informed by written instruction how to avoid only foods with a high Na content, 143 out-patients (84 males and 59 females, mean age 50.7 years, range 28-69) with DBP greater than or equal to 95 mm Hg randomly received for 4 weeks either metoprolol (M) 200 mg SR qd (67 patients), or S, 2 g bid to add to foods (76 patients). At the end of this period patients with DBP still greater than 90 mm Hg combined the two treatments for a further 4 weeks. Mean blood pressure (mm Hg), HR (bpm), 24-hrs urinary Na and K excretion were measured fortnightly. In comparison to pretreatment values MBP was significantly (P less than 0.01) reduced by both treatments, although to a greater extent in the M group already at the second week, without any further decrement thereafter. In the S group MBP decreased by 4.4 mm Hg and 27/76 patients were responders (DBP less than or equal to 90 mm Hg), while in the M group it was reduced by 9.0 mm Hg and 28/67 patients were responders. In the S group urinary Na excretion was significantly (P less than 0.01) lower than in the M group, and this difference was present until the end of period 1.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Dieta , Hipertensión/tratamiento farmacológico , Metoprolol/uso terapéutico , Potasio/administración & dosificación , Sodio en la Dieta/administración & dosificación , Adulto , Anciano , Presión Sanguínea/efectos de los fármacos , Ensayos Clínicos como Asunto , Femenino , Humanos , Hipertensión/fisiopatología , Masculino , Persona de Mediana Edad , NatriuresisRESUMEN
Serum insulin-like growth factor (IGF)-I and IGF-binding protein-3 levels were measured in two groups of postmenopausal women with advanced breast cancer, who received the aromatase inhibitor letrozole 0.5 or 2.5 mg p.o. once daily. Blood samples were obtained from 15 patients in each dose group at baseline, and one and three months after starting therapy. Circulating IGF-I and IGFBP-3 concentrations were determined by means of radioimmunoassay. In both dosage groups a statistically significant increase in the IGF-I levels was observed during three months of letrozole treatment (P=0.003). In addition, the multiple testing procedure yielded in the whole patient population a significant result in the comparison between mean IGF-I values after three months of therapy and those observed at baseline (P=0.004), the estimated average increase being of 24%. No significant result was obtained in the analysis for the dose effect (P=0.077) and for the time x dose interaction (P=0.208). Circulating IGFBP-3 levels did not appear to be affected by letrozole treatment in either of the dose groups. This is the first report concerning the short-term effects of letrozole on components of the IGF system in breast cancer patients; further investigations are warranted in order to confirm these preliminary data.
Asunto(s)
Inhibidores de la Aromatasa , Inhibidores Enzimáticos/farmacología , Proteína 3 de Unión a Factor de Crecimiento Similar a la Insulina/sangre , Factor I del Crecimiento Similar a la Insulina/metabolismo , Nitrilos/farmacología , Triazoles/farmacología , Anciano , Método Doble Ciego , Femenino , Humanos , Letrozol , Persona de Mediana Edad , PosmenopausiaRESUMEN
To investigate whether c-erbB 2 serum levels may be predictive of clinical response, progression-free and overall survival in postmenopausal women with advanced breast cancer hormonally treated, 265 patients enrolled in previous clinical trials were evaluated. C-erbB 2 serum levels were assessed before the start of treatment and in a subgroup of patients also at the first response evaluation. In addition, serum CA 15.3 levels were determined. The role of c-erbB 2 was investigated by means of multiple regression models in which both c-erbB 2 and CA 15.3 values were modelled as continuous variables together with other known prognostic factors. The failure probability tended to be higher in the presence of high c-erbB 2 levels, but the trend was not statistically significant; in contrast, significant results were obtained for progression-free survival (PFS,P <0.001) and overall survival (OS, P=0.014). The within-patient c-erbB 2 variation significantly predicted PFS (P=0.006) and OS (P=0.040). It is worth noting that c-erbB 2 and CA 15.3 baseline levels were significantly correlated and that the prognostic effect of c-erbB 2 tended to disappear in the presence of high CA 15.3 levels for PFS and OS.
RESUMEN
The incidence of stage IV breast cancer at diagnosis is low, representing about 8% of all new cases. We report on the results obtained with a new aromatase inhibitor, formestane (500 mg i.m. fortnightly), given as a first treatment to fifteen postmenopausal patients with metastatic breast cancer. The overall response rate was 40%, with one complete remission in a patient with soft tissue and bone lesions and five partial remissions. The drug was well. tolerated and no significant systemic or local side effects were observed. We conclude that first treatment of stage IV breast cancer appears to be feasible with a hormonal drug such as formestane.
RESUMEN
Anastrozole, letrozole and vorozole are new aromatase inhibitors with a nonsteroidal structure (NSS), and have been demonstrated to be highly effective and better tolerated than standard endocrine therapy with megestrol (megestrol acetate) and aminoglutethimide (AG). These agents are very potent and selective: all of them are capable of suppressing estrone (E1) and estradiol (E2) to the limit of sensitivity methods, and plasma estrone sulfate (E1S) levels are also suppressed. However, the fact that this potency has not led to any greater clinical efficacy, and that there is no relationship between estrogen suppression and clinical response, suggests that aromatase inhibitors may have additional mechanisms of action. A number of international, multicentre clinical trials have compared anastrozole, letrozole and vorozole with megestrol 160 mg/day or AG 500 mg/day plus hydrocortisone in patients with advanced breast cancer. Letrozole proved to be significantly more effective than megestrol but anastrozole had a greater effect on survival than either agent. However, letrozole therapy led to longer survival than that observed in patients treated with AG. The activity of vorozole was similar to that of megestrol and AG. These results have raised a number of questions. The first is how should the clinical results be evaluated, given that 'disease stabilisation lasting > or =6 months' has been considered a response? The second is how should these drugs be used, and whether there is a rationale for using them in combination or sequentially in the treatment of patients with advanced breast cancer? Finally, is the possible effect of formestane and vorozole on intratumoral aromatase an alternative or concomitant mechanism of action? Anastrozole, letrozole and vorozole will be compared with tamoxifen in postmenopausal patients with breast cancer in adjuvant and primary settings. However, we feel that concomitant biological and clinical studies should also be carried out in order to clarify the properties of these drugs and avoid possible risks for patients over time.
Asunto(s)
Antineoplásicos/uso terapéutico , Inhibidores de la Aromatasa , Neoplasias de la Mama/tratamiento farmacológico , Inhibidores Enzimáticos/uso terapéutico , Posmenopausia , Antineoplásicos/farmacología , Ensayos Clínicos como Asunto , Relación Dosis-Respuesta a Droga , Inhibidores Enzimáticos/farmacología , Femenino , Humanos , Estudios Multicéntricos como AsuntoRESUMEN
The combination flumethasone pivalate + iodochlorohydroxychinoline drops was used in 40 patients, 24 males and 16 females, mean age 42.6 years, suffering from infectious enanthema (35%), periodontitis (30%), aphthous stomatitis (25%) and abscess due to prosthesis (10%). After application of 2-3 drops of the combination t.i.d. for 2-7 days, satisfactory results were obtained in all the patients. Tolerance was good; mild unwanted effects occurred in 2 patients (5.0%). Thus the combination flumethasone pivalate + iodochlorohydroxychinoline appears to be very effective in the treatment of oral diseases because its action is more rapid and stronger than that of other currently used drugs.
Asunto(s)
Flumetasona/análogos & derivados , Enfermedades de la Boca/tratamiento farmacológico , Absceso/tratamiento farmacológico , Absceso/etiología , Adolescente , Adulto , Anciano , Niño , Dentaduras/efectos adversos , Femenino , Flumetasona/uso terapéutico , Humanos , Infecciones/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Enfermedades de la Boca/patología , Mucosa Bucal/patología , Periodontitis/tratamiento farmacológico , Estomatitis Aftosa/tratamiento farmacológicoRESUMEN
In this multicentre trial, 1072 hospitalized children, 573 boys and 499 girls (847 of whom were aged less than 6 years), affected by respiratory tract (376 patients) or ENT (696 patients) infections were treated for 10 days with cefroxadine per os, at an average dose of 650 mg/day (325 mg every 12 h corresponding to 25 mg/kg b.w.). Most patients (1047; 97.7%) completed the trial, while 25 patients were withdrawn from the study (20 patients for viral diseases and 5 for side-effects). Of the patients affected by respiratory tract infections, 361 completed the trial and 342 of them (94.7%) were cured in 6.0 days on average. Of the patients affected by ENT infections, 686 completed the trial and 649 of them (94.6%) were also cured in an average of 6.0 days. In the two groups the signs and symptoms of the disease significantly (p less than 0.001) decreased by the end of the study. Some patients (80; 7.6%) complained of side-effects, mainly gastric discomfort (4.9%), skin rash (2.2%) and glossitis (0.5%). In conclusion, cefroxadine exerts a satisfactory antibacterial action with only a few days of treatment, and it appears to be very well tolerated.
Asunto(s)
Infecciones Bacterianas/tratamiento farmacológico , Cefalosporinas/uso terapéutico , Cefradina/uso terapéutico , Enfermedades Otorrinolaringológicas/tratamiento farmacológico , Infecciones del Sistema Respiratorio/tratamiento farmacológico , Cefradina/análogos & derivados , Niño , Preescolar , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Enfermedades Otorrinolaringológicas/microbiología , Infecciones del Sistema Respiratorio/microbiologíaRESUMEN
Breast cancer is the most common malignant neoplasm affecting women in Western countries, and most new cases are manifested during the postmenopausal period. The clinical results obtained with aminoglutethimide, and later with formestane, have established aromatase inhibition as one of the major therapeutic options in hormone-dependent advanced disease. Nevertheless, the lack of specificity of aminoglutethimide and the less than optimal oral activity of formestane soon led to further efforts to find a potent, highly selective, orally active, side-effect-free aromatase inhibitor for use in postmenopausal women with advanced breast cancer. Here we review the available data on three new, competitive non-steroidal aromatase inhibitors--letrozole, vorozole and anastrozole--which are approaching the point of detailed pharmacologic and clinical evaluation. Preliminary data have confirmed the high potency and selectivity of these endocrine agents, but their antitumor activity still remains to be completely defined. Challenges given by these novel aromatase inhibitors are discussed taking into account the biologic implications related to their mechanism of action and their future use in the management of breast cancer.
Asunto(s)
Antineoplásicos/farmacología , Inhibidores de la Aromatasa , Neoplasias de la Mama/tratamiento farmacológico , Drogas en Investigación/farmacología , Anastrozol , Antineoplásicos/química , Antineoplásicos/uso terapéutico , Drogas en Investigación/química , Drogas en Investigación/uso terapéutico , Femenino , Humanos , Letrozol , Nitrilos/farmacología , Triazoles/farmacologíaRESUMEN
In a double-blind trial, 545 out-patients with essential hypertension received 25 mg/day chlorthalidone alone (274 patients) or in fixed combination with 200 mg/day slow-release metoprolol (271 patients) for 8 weeks. Both treatments significantly (P less than 0.001) decreased systolic and diastolic blood pressure; 45.6% of patients receiving chlorthalidone and 82.5% receiving combined therapy had a diastolic blood pressure of less than 95 mmHg. Patients not controlled by chlorthalidone or chlorthalidone plus metoprolol subsequently received chlorthalidone plus metoprolol (137 patients) or chlorthalidone plus metoprolol plus a third drug (34 patients), respectively, for 8 weeks. A total of 79.5% of patients receiving chlorthalidone plus metoprolol and 61.8% receiving chlorthalidone plus metoprolol plus a third drug had a diastolic blood pressure of less than 95 mmHg. Only 5.9% of patients experienced mild to moderate side-effects. Plasma potassium levels significantly (P less than 0.01) decreased during the first 8 weeks only. It is concluded that a diuretic alone or in fixed combination with a beta-blocker is effective in the long-term treatment of arterial hypertension.
Asunto(s)
Clortalidona/uso terapéutico , Hipertensión/tratamiento farmacológico , Metoprolol/uso terapéutico , Presión Sanguínea/efectos de los fármacos , Ensayos Clínicos como Asunto , Preparaciones de Acción Retardada , Método Doble Ciego , Quimioterapia Combinada , Estudios de Seguimiento , Humanos , Metoprolol/administración & dosificación , Persona de Mediana Edad , Distribución AleatoriaRESUMEN
A fixed combination of metoprolol slow-release 200 mg and chlorthalidone 25 mg was given once daily over a 3 months period in forty out-patients with mild-to-moderate arterial hypertension stage I or II WHO. The combination elicited a clear-cut antihypertensive effect lasting at least 24 hours after drug. As compared with pre-treatment values, systolic and diastolic blood pressures were gradually reduced within the first month of treatment, remaining nearly constant in the following 2 months. Treatment was well tolerated by all patients. Neither serum potassium nor any other laboratory test (creative, glucose, uric acid, etc) showed significant changes. In conclusion, slow-release metoprolol fixed association with chlorthalidone provides a safe and effective treatment of arterial hypertension even on a long-term basis. The once daily dosing schedule may considerably improve patient's compliance.
Asunto(s)
Clortalidona/administración & dosificación , Hipertensión/tratamiento farmacológico , Metoprolol/administración & dosificación , Propanolaminas/administración & dosificación , Adulto , Anciano , Arterias , Quimioterapia Combinada , Humanos , Cuidados a Largo Plazo , Persona de Mediana EdadRESUMEN
To investigate whether a K-rich/Na-poor salt is able to reduce blood pressure, 10 mildly hypertensive inpatients (six males) aged 28-53 years, with supine diastolic blood pressure (DBP) greater than 95 mmHg after 5 days of hospitalization, on a standard diet containing about 20 mmol Na plus 4 g common salt (CS) were randomly given, in double-blind conditions, 2 g twice daily of either CS (five patients) or K-rich/Na-poor salt (five patients) to add to food for a further 8 days. Mean blood pressure was significantly (P less than 0.01) reduced to a similar extent in both groups in the first 4 days, and declined significantly (P less than 0.01) only in the K/Na group in the following 8 days, reaching values significantly (P less than 0.01) lower than those of the CS group. The heart rate did not change significantly while body weight decreased to a similar extent in both groups. Urinary sodium excretion was similarly and significantly (P less than 0.01) reduced in both groups in the first 4 days (CS 100.8 +/- 7.9 and K/Na 100.2 +/- 11.0 mmol/24 h, and remained unchanged in the CS group (109.9 +/- 4.3 mmol/24 h) but declined significantly (P less than 0.05) by about 50% in the K/Na group (62.9 +/- 3.6 mmol/24 h) in the following 8 days. Plasma renin activity (PRA) and plasma noradrenaline did not differ significantly between the two groups, nor among the days of treatment, but the mean blood pressure response to mental stress was reduced significantly (P less than 0.4) in the Na/K group compared with the CS group.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Dieta Hiposódica , Hipertensión/dietoterapia , Potasio/administración & dosificación , Adulto , Ensayos Clínicos como Asunto , Condimentos , Método Doble Ciego , Hospitalización , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Blood pressure was recorded for 20 years in 138 nuns in a secluded order and in 126 lay women taken as controls. During the study period none of the nuns or control women smoked, took oral contraceptives or changed residence. Diet was unrestricted and comparable in the two groups. Subjects of both groups were consecutively enrolled without any selection parameters. During the 20 years of observation, systolic and diastolic blood pressure rose with age in the control women but remained almost unchanged in the nuns. The mean of the regression slope of systolic and diastolic blood pressure versus age, which was calculated for each subject, was 0.089 and 0.054 respectively in the nuns, as opposed to 2.171 and 0.742 in the lay women (both P < 0.001). Secluded nuns, who spend almost all their time in silence and prayer in the virtual absence of company apart from when attending religious celebrations, thus showed almost no change in blood pressure with age over a 20-year period. The results support the hypothesis that, at least in women, everyday stress may be a determinant of the progressive increase in blood pressure with ageing.