RESUMO
Long-acting beta(2)-adrenoceptor agonists attenuate the allergen-induced late asthmatic reaction. We evaluated whether other mechanisms in addition to airway smooth muscle relaxation may be implicated in this protective effect. The effects of formoterol (Foradil Aerolizer(TM), 24 microg dry powder) on the late asthmatic reaction were assessed by a randomised crossover factorial study in 24 patients with asthma. Four challenge/treatment combinations were tested: (A) saline/placebo, (B) saline/formoterol, (C) allergen/placebo, (D) allergen/formoterol. Formoterol and placebo were administered double blind after the last inhalation of the allergen or saline. FEV(1) was measured up to 32 h. The bronchodilator effect of formoterol was estimated as (B-A) and the overall protective effect as (D-C). The effect not due to bronchodilation was estimated as [(D-C)-(B-A)]/2. The bronchodilator effect of formoterol was statistically significant up to 5h (all P< or =0.015). Formoterol significantly attenuated the late asthmatic reaction between 3 and 32 h after allergen inhalation (all P< or =0.0012). The difference between this protective effect and the bronchodilator effect was statistically significant at 5 h and between 7 and 28 h after allergen inhalation (all P< or =0.035). Our results suggest that functional antagonism may not be the sole mechanism by which formoterol attenuates the allergen-induced late asthmatic reaction.
Assuntos
Agonistas Adrenérgicos beta/farmacologia , Alérgenos/efeitos adversos , Asma/tratamento farmacológico , Asma/fisiopatologia , Broncodilatadores/farmacologia , Etanolaminas/farmacologia , Adolescente , Adulto , Asma/etiologia , Brônquios/efeitos dos fármacos , Broncoconstritores/administração & dosagem , Broncoconstritores/farmacologia , Estudos Cross-Over , Método Duplo-Cego , Feminino , Volume Expiratório Forçado/efeitos dos fármacos , Fumarato de Formoterol , Humanos , Masculino , Cloreto de Metacolina/administração & dosagem , Cloreto de Metacolina/farmacologia , Relaxamento Muscular/efeitos dos fármacos , Músculo Liso/efeitos dos fármacos , Fatores de TempoRESUMO
Extensive ablation of renal mass in experimental animals leads to progressive glomerulosclerosis and chronic renal failure (CRF). Clinical studies are far from answering the question whether patients with reduced renal mass are at risk of developing progressive CRF. The aim of our study was to examine the morphological and functional aspects of the remnant kidney in a group of patients who underwent unilateral nephrectomy for renal tuberculosis: 313 patients (161 M, 152 F) mean age 57.2 +/- 10.7, were examined after a period ranging from 13.56 to 591.2 months. All patients were on ad libitum diet. Hypertension was found in 34.19% of the patients; SBP was 155.29 +/- 19.9 mmHg and DBP was 92.74 +/- 13.07 mmHg. Estimation of renal size performed by ultrasound scanner gave the following results: length 116.78 +/- 8.99 mm; width 58.24 +/- 7.21 mm; thickness 17.88 +/- 1.96 mm. Kidney function assessed by serum creatinine levels showed a mean level of 1.28 +/- 0.53 mg%. Forty-two patients (13.41%) had serum levels > 1.5 mg% but 18 of them had nonconcomitant systemic or renal involvement. Microalbuminuria determined by RIA assay was found in 50.5% of the patients. In our group of patients renal functional impairment was low and hyperfiltration expressed as microalbuminuria does not appear to be a primary factor in the progression of renal failure.
Assuntos
Falência Renal Crônica/fisiopatologia , Rim/fisiopatologia , Nefrectomia , Tuberculose Renal/cirurgia , Creatinina/sangue , Feminino , Seguimentos , Humanos , Hipertrofia , Rim/patologia , Falência Renal Crônica/epidemiologia , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Fatores de TempoRESUMO
In order to evaluate the prognostic factors concerning the rate of progressive deterioration of renal function, we made an inductive analysis of the behaviour of 456 patients in a multicentre, formal prospective trial aimed at clarifying the possible role of protein restriction in retarding the progression of chronic renal insufficiency (CRI). The main clinical and laboratory findings in patients whose plasma creatinine (PCr) levels doubled in comparison with baseline randomization values or who needed dialysis within 24 months after onset of the study were compared with those of the other patients. In addition, independently of the assigned diet, we tested the main variables that might affect CRI progression (sex, systolic and diastolic blood pressure, change in body weight, hematocrit, calcium-phosphate product, proteinuria, protein catabolic rate, total cholesterol and triglycerides). We used multiple regression analyses and also plotted the mean values of these parameters in each patient against an estimate of the deterioration of chronic renal failure based on the difference between the final and the initial reciprocal of the PCr and the creatinine clearance (CCr) levels. A descriptive analysis of the behaviour of PCr in the three CRI groups and in the four underlying diseases groups was made. PCr levels at entry, underlying disease and proteinuria were prognostic factors for CRI progression. The increase in PCr was 0.0102 mg/dl/month in patients with nephrosclerosis, 0.0203 mg/dl/month in interstitial nephropathy, 0.0360 mg/dl/month in glomerulonephritis and 0.0704 mg/dl/month in polycystic kidney disease.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Falência Renal Crônica/fisiopatologia , Adolescente , Adulto , Idoso , Pressão Sanguínea/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Análise de Regressão , Fatores de RiscoRESUMO
In an open, randomized, comparative, between-patient trial, 45 postmenopausal women were treated for 4 months with cyclical transdermal oestradiol 0.05 mg per day or oral conjugated equine oestrogens 0.625 mg per day, in both cases, plus, medroxyprogesterone acetate 10 mg per day on the last 8 days of each cycle. Similar relief from postmenopausal symptoms was obtained with both treatments. Post-treatment histological evaluation of the endometrium did not reveal neoplastic or hyperplastic change in any patient. Early follicular-phase plasma oestradiol levels were observed only after transdermal oestradiol. There was a significant reduction in serum total cholesterol and LDL cholesterol in both treatment groups, with no difference between treatments, whereas serum triglyceride levels were decreased only by transdermal oestradiol. Plasma calcium and phosphorus fell significantly and serum intact parathyroid hormone rose significantly, with no difference between the therapies. No significant changes were observed in clotting factors. Transdermal oestradiol appears to be an effective and safe hormonal replacement therapy, and this route of administration may be responsible for the more useful action of the drug on serum lipids and plasma oestradiol levels.
Assuntos
Estradiol/administração & dosagem , Terapia de Reposição de Estrogênios , Estrogênios Conjugados (USP)/administração & dosagem , Medroxiprogesterona/administração & dosagem , Menopausa/efeitos dos fármacos , Administração Cutânea , Administração Oral , Adulto , Quimioterapia Combinada , Estradiol/uso terapêutico , Estrogênios Conjugados (USP)/uso terapêutico , Feminino , Humanos , Medroxiprogesterona/uso terapêutico , Pessoa de Meia-IdadeRESUMO
Antidepressant drugs are increasingly used in the management of chronic pain. They are mainly prescribed for cancer-related pain and central pain, e.g. phantom or stump pain, post-herpetic neuropathy. However, no controlled clinical trials have validated their in either pathology. Thus, physicians still do not know whether antidepressants are really effective and which might be best. It is still debated whether the effect of antidepressants in the management of chronic pain is limited to the amelioration of frequently concomitant depression or extends to pain itself. To verify both the analgesic effect of tricyclic antidepressants, and the possible relationship between their antidepressant effect and the relief of central pain, we carried out a randomized, within-patient (cross-over) placebo-controlled study in patients suffering from central pain. The results clearly indicate the better analgesic effect of tricyclic antidepressants over placebo (p less than 0.0001). Within the antidepressants tested, chlorimipramine, a blocker of serotonin reuptake, is significantly more effective (p less than 0.0001) than notriptyline, a blocker of noradrenaline reuptake. Finally, the antinociceptive effect is independent of the effects of the two drugs on the symptoms of depression.
Assuntos
Clomipramina/uso terapêutico , Nortriptilina/uso terapêutico , Dor/tratamento farmacológico , Adulto , Clomipramina/normas , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nortriptilina/normas , PlacebosRESUMO
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)
Assuntos
Envelhecimento , Pressão Sanguínea , Adulto , Dieta , Feminino , Seguimentos , Humanos , Estilo de Vida , Pessoa de Meia-Idade , Gravidez , Religião , Estresse Psicológico/fisiopatologiaRESUMO
To evaluate the effects of the chronic administration of the fixed combination slow-release, oxprenolol 160 mg and chlorthalidone 20 mg on left ventricular hypertrophy, ten hypertensive out-patients, with left ventricular hypertrophy documented by left ventricular mass index (LVMI) greater than 130 g/m2, were studied. After a two-week placebo period, patients were given the study medication, once daily for six months. Blood pressure and heart rate were measured, 24 h after-dosing, at the end of placebo and thereafter every month. A m-mode echocardiographic examination was performed at the end of the placebo period, after 1 month of active treatment and at the end of the study. In comparison with placebo, the study medication induced a significant reduction (p less than 0.01) of systolic and diastolic blood pressure, 24 h after dosing, after 1 month of treatment (from 181.0 +/- 18.5/108.5 +/- 12.0 to 146.5 +/- 10.8/94.0 +/- 7.7 mmHg), and this reduction was maintained until the end of the study (142.0 +/- 14.0/90.0 +/- 8.2 mmHg). At the 6th month and in comparison with placebo, a significant (p less than 0.01) reduction of left ventricular mass (LVM) and of LVMI was observed (LVM: from 295.9 +/- 113.8 to 221.5 +/- 66.1 g; LVMI: from 158.1 +/- 39.0 to 126.2 +/- 35.8 g/m2. In conclusion, our results confirm the good antihypertensive efficacy of the fixed combination slow-release oxprenolol and chlorthalidone and show that the study medication is able to induce a regression of left ventricular hypertrophy, in hypertensive patients.
Assuntos
Cardiomegalia/tratamento farmacológico , Clortalidona/uso terapêutico , Hipertensão/complicações , Oxprenolol/uso terapêutico , Adulto , Idoso , Glicemia/metabolismo , Pressão Sanguínea/efeitos dos fármacos , Cardiomegalia/etiologia , Clortalidona/administração & dosagem , Clortalidona/efeitos adversos , Creatinina/sangue , Preparações de Ação Retardada , Ecocardiografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Oxprenolol/administração & dosagem , Oxprenolol/efeitos adversos , PosturaRESUMO
To assess the efficacy and tolerability of two doses of chlorthalidone (CHL) and slow-release (SR) metoprolol (MET) given in fixed combination (standard dose: CHL 25 mg and MET 200 mg; lower dose: CHL 12.5 mg and MET 100 mg), a multicenter (5 Centers), double-blind, between-patients study was planned. Seventy-three mild to moderate hypertensive patients, 45 males and 28 females, aged 25-68 years (mean 51.4), at WHO stage I or II, were enrolled into the study. After a 2-week placebo wash-out period, eligible patients were randomly given either of the two drugs for six weeks: 33 were given the standard dose and 40 the lower one. Every 2 weeks, in the morning and 24 h after-dosing lying and standing systolic (SBP), diastolic blood pressure (DBP) and heart rate (HR) were recorded at rest. At the end of the placebo period and at the end of the study 24 h after-dosing a sub-maximal bicycle ergometer exercise test was performed. In comparison with placebo, both doses induced a significance decrease (p less than 0.01) in lying and standing SBP, DBP and HR, as well as in peak-exercise SBP, HR and pressure-rate product. Furthermore, a significant difference (p less than 0.05) of the higher dose versus the lower one was also observed at the end of the study in the above-mentioned parameters except for SBP at rest and at peak exercise and standing HR at rest.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Clortalidona/uso terapêutico , Hipertensão/tratamento farmacológico , Metoprolol/uso terapêutico , Adulto , Idoso , Método Duplo-Cego , Combinação de Medicamentos , Teste de Esforço , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
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.
Assuntos
Envelhecimento/fisiologia , Pressão Sanguínea/fisiologia , Adulto , Catolicismo , Feminino , Humanos , Estilo de Vida , Pessoa de Meia-IdadeRESUMO
Two-hundred-and-three female patients (mean age: 58 yrs; SD: 8.2 yrs) suffering from osteoarthritis entered this late phase IV multicentre, stratified according to previous therapy (e.g. ketoprofen, naproxen, aspirin, indomethacin or indoprofen), randomized, double-blind, between within-patient trial of 2-week duration. Each patient received either diclofenac SR 100 mg/day (D), piroxicam 20 mg/day (P), or placebo (P1 by oral route. Clinical evaluation (functional class; pain assessment; osteoarthritic condition; joint motility and stiffness) was performed at entry, as well as after the first and the second week. Patient compliance and reported signs and symptoms were recorded after the first week and at the end of the trial. Patient preference, as regards previous therapy, and global evaluation (both by the physicians and the patients) were checked at the end of the trial. The clinical evaluation showed a superiority of D and P over P1. No difference was seen between the two active drugs. Placebo effect was very strong. Global evaluation was significantly in favour of D and P. Patient compliance was extremely good (greater than or equal to 95%). Diclofenac was preferred to naproxen, aspirin and indomethacin, while piroxicam and placebo were preferred only to aspirin. The tolerability of the two active drugs was good and comparable. A significantly lower number of patients complaining of unwanted effects (u.e.) was detected in the placebo group. The number of patients withdrawn for u.e. was similar in the three trial groups.
Assuntos
Osteoartrite/tratamento farmacológico , Cooperação do Paciente , Adulto , Idoso , Aspirina/administração & dosagem , Aspirina/uso terapêutico , Ensaios Clínicos como Assunto , Diclofenaco/administração & dosagem , Diclofenaco/uso terapêutico , Método Duplo-Cego , Esquema de Medicação , Humanos , Indometacina/administração & dosagem , Indometacina/uso terapêutico , Indoprofen/administração & dosagem , Indoprofen/uso terapêutico , Cetoprofeno/administração & dosagem , Cetoprofeno/uso terapêutico , Pessoa de Meia-Idade , Naproxeno/administração & dosagem , Naproxeno/uso terapêutico , Dor , Piroxicam , Tiazinas/administração & dosagem , Tiazinas/uso terapêuticoRESUMO
A new pain rating scale, Analogue Chromatic Continuous Scale (ACCS), has been developed. The ACCS was tested in fifty consecutive patients suffering from pain of different origins, and compared with a simple descriptive scale (SDS) and a traditional 100 mm visual analogue scale (VAS). VAS and ACCS values showed a highly significant, positive correlation (r = 0.947, P less than 0.001). The means of the VAS and ACCS values, either considered as a whole or stratified according to SDS scores, did not differ significantly. The ACCS proved to be more sensitive than VAS (P less than 0.05), allowing a greater discrimination of grades of pain. Furthermore, the ACCS is very easy to use.
Assuntos
Dor/diagnóstico , Adolescente , Adulto , Idoso , Criança , Equipamentos e Provisões , Estudos de Avaliação como Assunto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Dor/classificaçãoRESUMO
Regional intravenous guanethidine blocks and stellate ganglion blocks have been compared in a randomized trial. Nineteen patients, randomly allocated to two groups of therapy and exhibiting severe reflex sympathetic dystrophy following peripheral nerve lesions, have been treated. The performance of the intravenous guanethidine block is of longer duration and superior to stellate ganglion block, as regards some early pharmacological effects (skin temperatures and amplitude of plethysmographic waves recorded before blockade and 15 min, 60 min, 24 h, 48 h after institution of the block). In fact the intravenous guanethidine group shows a persistent and significant increase of the skin temperature and of the plethysmographic traces in the blocked side 24 h and 48 h after blockade in comparison with the patients treated with stellate ganglion block. Concerning the therapeutic effects (changes in pain scores and clinical signs--hyperpathia, allodynia, vasomotor disturbances, trophic changes, oedema and limited motion), recorded at the end of treatment and 1 month and 3 months follow-up, an intravenous guanethidine block carried out every 4 days up to a total of 4 blocks is comparable with a stellate ganglion block every day up to a total of 8 blocks. The results of this study show that regional sympathetic block with guanethidine is a good therapeutic tool in the treatment of reflex dystrophies, especially on account of its negligible risks and contraindications.