RESUMO
OBJECTIVE: In order to assess the efficacy and tolerability of leuprorelin acetate depot in pre-operative flattening of the endometrium prior to hysteroscopic endometrial ablation, 94 patients from eight centres were included in the per protocol analysis. MATERIAL AND PATIENTS: The patients included were pre- or peri-menopausal, had completed their family planning and had intractable uterine bleeding. The primary target criterion was the reduction in maximum endometrial thickness after two injections of leuprorelin acetate depot with an interval of four weeks between injections. Surgery took place two weeks after the second injection. RESULTS: Sufficient pre-treatment was achieved in 91.5% of the patients with > 50% decrease and/or a type 1 endometrium according to sonographic and/or endometrial atrophy (Score 11) according to the central histological evaluation. The endometrium was flattened by a mean of 4.0 +/- 4.1 mm. In terms of clinical response, amenorrhoea, hypomenorrhoea or normal menstruation were achieved after endometrial ablation. Hence 91.5% of patients benefited from the overall treatment after six weeks and still 83% after six months. The trial medication was well tolerated overall. The most common side-effect described was hot flushes which could be attributed to the deliberate oestrogen withdrawal. CONCLUSION: In view of the good study results, hormone-suppressive pretreatment of the endometrium can be recommended prior to elective ablation. Surgery should take place during the oestrogen-suppressed phase.
Assuntos
Hiperplasia Endometrial/cirurgia , Histeroscopia , Leuprolida/administração & dosagem , Menorragia/cirurgia , Metrorragia/cirurgia , Cuidados Pré-Operatórios , Adulto , Biópsia , Preparações de Ação Retardada , Esquema de Medicação , Hiperplasia Endometrial/patologia , Endométrio/efeitos dos fármacos , Endométrio/patologia , Endométrio/cirurgia , Feminino , Humanos , Leuprolida/efeitos adversos , Menorragia/patologia , Metrorragia/patologia , Pessoa de Meia-IdadeRESUMO
A 32-year-old man presenting with typical features of Cushing's syndrome showed baseline cortisol and ACTH values indicating ACTH-dependent disease. Dynamic function tests (dexamethasone, corticotropin releasing hormone (CRH), desmopressin), were suggestive of paraneoplastic ectopic ACTH production. However, inferior petrosal sinus (IPS) ACTH sampling demonstrated a maximum baseline central (363 pmol/l)-peripheral (19 pmol/l) ACTH gradient of 19.1 for the right IPS, conventionally suggestive of Cushing's disease. However, again, IPS ACTH level did not increase after CRH stimulation. Magnetic resonance imaging, while showing no evidence of an intrasellar tumour, revealed an 1.5 x 1.0 cm mass in the left sphenoid sinus which was initially interpreted as most probably being a mucosal polyp. After neurosurgical removal of the tumour, transient secondary adrenal insufficiency was present. The structure and immunostaining characteristics of the tumour demonstrated an ACTH cell adenoma of the pituitary. Ectopic ACTH-secreting pituitary adenomas may cause significant difficulties in differential diagnosis, localisation and appropriate therapy. Thus, although these tumours are rare, they should be included in the list of possible causes of ACTH-dependent Cushing's syndrome.
Assuntos
Adenoma/complicações , Hormônio Adrenocorticotrópico/metabolismo , Síndrome de Cushing/etiologia , Proteínas de Neoplasias/metabolismo , Neoplasias Hipofisárias/complicações , Síndrome de ACTH Ectópico/diagnóstico , Adenoma/metabolismo , Testes de Função do Córtex Suprarrenal , Adulto , Síndrome de Cushing/diagnóstico , Diagnóstico Diferencial , Seguimentos , Humanos , Imageamento por Ressonância Magnética , Masculino , Hipófise/patologia , Neoplasias Hipofisárias/metabolismoRESUMO
Both, impaired beta-cell function and insulin resistance, predominantly of the skeletal muscle, are considered to be the key factors in the pathogenesis of type-2 diabetes (non-insulin-dependent diabetes; NIDDM). In the early stage of the disease, impaired insulin-mediated glucose disposal is accompanied by increased insulin secretion and hyperinsulinaemia. The thiazolidinediones (e.g. troglitazone), by improving insulin sensitivity of target tissues, appear to be a novel pathophysiologically interesting approach for the treatment of patients with NIDDM or impaired glucose tolerance. Troglitazone mainly elicits the following actions: Enhancement of insulin-mediated glucose disposal in patients with insulin resistance, impaired glucose tolerance and NIDDM, reduction of hyperglycaemia (blood glucose; HbA1c) and concomitant hyperinsulinaemia, improvement of dyslipidaemia in NIDDM. These actions are attained with monotherapy (200-600 mg once daily; plasma concentrations 0.3-3.0 micrograms/ml) or, with increased effects, when troglitazone is added to previously insufficient treatment with sulfonylureas or insulin. Potentially therapeutic actions with clinical relevance include (a) improvement of insulin resistance-associated hyperglycaemia-independent states of dyslipidaemia, (b) inhibition of LDL-oxidation and (c) amelioration of function and/or protection of beta-cells, an effect indicating to a beneficial modulation of the second pathogenetic relevant factor of NIDDM. Troglitazone appears to be well tolerated by the majority of patients. Post-marketing reports of partly severe liver injury including deaths from liver failure among Japanese and U.S. patients taking troglitazone require a critical evaluation of the benefit to risk ratio of the drug and a careful monitoring of the patients.
Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Tiazóis/uso terapêutico , Animais , HumanosRESUMO
Earlier studies suggest that cardiovascular responses in the laboratory and in the field are likely to be related when the laboratory tasks involve active coping, when the field measure is taken continuously, and when there is allowance for the effects of autocorrelation and physical activity on the ambulant cardiovascular measure. These studies lead to the hypothesis that the hyperreactivity common to the laboratory and to the field has a beta-adrenergic basis. We examined the heart rate variability of 16 hyperreactive and 16 hyporeactive subjects over an 8-hour period while they were receiving either a placebo or a cardio-selective beta-blocking drug (Bisoprolol) in a double-blind crossover design. Subjects were classified on the basis of their heart rate and systolic blood pressure responses to a complex self-paced, reaction-time task. Response in the field was assessed from the standard deviation of the raw heart rate series, after allowance for the serial dependency in the data using autoregressive methods and, when allowance was made for physical activity, assessed from the muscle activity of the thigh. As predicted, on placebo hyperreactive subjects had markedly more variable heart rates, particularly when allowance was made for physical activity. Although not confirmed by a significant interaction effect, this difference largely disappeared under beta-blockade.
Assuntos
Nível de Alerta/efeitos dos fármacos , Bisoprolol/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Frequência Cardíaca/efeitos dos fármacos , Meio Social , Adaptação Psicológica/efeitos dos fármacos , Adolescente , Adulto , Monitores de Pressão Arterial , Método Duplo-Cego , Feminino , Humanos , MasculinoRESUMO
A randomised controlled multicentre trial was performed in 160 patients with gastric ulcer, proved by endoscopy and biopsy, to compare ulcer healing with sucralfate and ranitidine (double blind double dummy design) and to assess the effect of maintenance treatment with sucralfate on ulcer recurrence (double blind placebo controlled design). The healing rates were similar with 4 g sucralfate suspension per day and 300 mg ranitidine per day (82% and 88% after 12 weeks, respectively). Of the 109 patients with healed ulcers, 92 were entered into the maintenance trial and treated with sucralfate tablets (2 g per day) or placebo tablets. Maintenance treatment with sucralfate delayed symptoms of gastric ulcer recurrence. Lifetable analysis showed significant differences between sucralfate and placebo, both after six months (p = 0.018) and after 12 months (p = 0.044). The rates of symptom recurrences were 13% and 34% after six months and 34% and 55% after 12 months for sucralfate and placebo, respectively. The rate of asymptomatic recurrences after 12 months was similar in the two groups (9% and 10%, respectively). The recurrence rate was higher in patients who had never taken non-steroidal anti-inflammatory drugs than in those who had but had stopped on admission to the study. It was also higher in patients with recurrent ulcer and in those with scarring deformation and narrowing of the pylorus. Maintenance treatment with sucralfate slowed the appearance of symptom recurrences of gastric ulcer.
Assuntos
Úlcera Gástrica/tratamento farmacológico , Sucralfato/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Recidiva , Úlcera Gástrica/prevenção & controleRESUMO
Forty outpatients suffering from angina pectoris due to coronary artery disease and concomitant reversible. chronic obstructive bronchitis were treated with the beta1-selective beta-blockers atenolol (50 mg) and bisoprolol (5 mg) for 6 months in each case, following a randomized, double-blind crossover study design. Lung function tests were carried out by means of whole-body plethysmography before and then several times during treatment. 2 to 4 h after drug intake (once daily in the morning). The main target variables for the factorial analysis of variance for comparison of the two beta-blockers were the airway resistance (AWR), the forced expiratory volume in the first second (FEV1), and the peak expiratory flow rate (PEFR). Bicycle ergometry was performed before and after therapy in order to check the cardiovascular effects of the two beta-blockers. The patients were questioned as to their angina pectoris and bronchitis symptoms at the monthly check-ups. There was no difference between the two beta-blockers (p > 0.05), both causing a slight increase in AWR, which increased with therapy duration, and a small but significant decrease in FEV1 and PEFR (p < 0.01). The bronchitis symptoms were not affected; however, seasonal influences were detected. Atenolol and bisoprolol had comparably pronounced effects on the cardiovascular parameters during ergometry (blood pressure, heart rate, W x min product, and ST-segment depression) and the frequency of angina pectoris attacks. Even beta1-selective beta-blockers may cause an impairment of lung function in patients with chronic obstructive bronchitis. This may be due to the presence of beta1-adrenoceptors in the bronchial tissue. Fifty milligrams of atenolol and 5 mg of bisoprolol once per day are effective in the treatment of angina pectoris.
Assuntos
Antagonistas Adrenérgicos beta/uso terapêutico , Angina Pectoris/tratamento farmacológico , Atenolol/uso terapêutico , Bisoprolol/uso terapêutico , Bronquite/tratamento farmacológico , Antagonistas de Receptores Adrenérgicos beta 1 , Adulto , Idoso , Resistência das Vias Respiratórias/efeitos dos fármacos , Resistência das Vias Respiratórias/fisiologia , Pressão Sanguínea/efeitos dos fármacos , Pressão Sanguínea/fisiologia , Estudos Cross-Over , Método Duplo-Cego , Teste de Esforço/efeitos dos fármacos , Feminino , Volume Expiratório Forçado/efeitos dos fármacos , Volume Expiratório Forçado/fisiologia , Frequência Cardíaca/efeitos dos fármacos , Frequência Cardíaca/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Receptores Adrenérgicos beta 1/fisiologiaRESUMO
In a multi-center study, 188 patients with mild to moderate essential hypertension were treated with the beta-1 selective beta blocker bisoprolol. Treatment was started with 5 mg bisoprolol once a day; if the aim of therapy, namely normalising (less than or equal to 90 mmHg) the diastolic blood pressure at rest (DBP-R) 24 hours after drug intake was not achieved, the dose was increased every two weeks to a maximum of 20 mg. With the individual dose established in this way, the patients were admitted to long-term treatment that was scheduled to last one year. Prior to and during bisoprolol therapy, bicycle ergometry studies were carried out up to a maximum of 100 watts. After only two weeks on 5 mg bisoprolol, both resting and exercise blood pressures were clearly reduced. By means of success-related dose increments, normalisation of the DBP-R was achieved in 79% of the patients by the end of the 6th week. The percentage of patients manifesting load-positive blood pressure reactions during exercise was reduced from 63 to 18%. On conclusion of one year of treatment, 33%, 56% and 11% of the patients were receiving 5 mg, 10 mg and 20 mg bisoprolol, respectively. On the basis of subjective and objective parameters, including laboratory examinations, bisoprolol was seen to be well tolerated even over the long term.
Assuntos
Pressão Sanguínea/efeitos dos fármacos , Ritmo Circadiano/efeitos dos fármacos , Teste de Esforço , Hipertensão/tratamento farmacológico , Propanolaminas/uso terapêutico , Adolescente , Adulto , Idoso , Bisoprolol , Ensaios Clínicos como Assunto , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
In a 4-week randomized, double-blind study, 87 patients with essential hypertension received either 10 mg bisoprolol (B) or 100 mg metoprolol (M) once daily (o.d.). The effects of the beta blockers on systolic blood pressure, heart rate and rate-pressure product during exercise, 24 h (E2) and 3 h (E3) after administration (p.a.) were compared with the values obtained in the baseline exercise test (E1). 24 hours p.a. the effects of B were significantly stronger than of M (E1-E2: B vs M; P less than 0.01) whereas 3 h p.a. no significant differences were detectable between B and M. The residual effects 24 h p.a. in relation to the effects 3 h p.a. (E1-E2/E1-E3) were significantly greater with B (86-93%) than with M (53-66%). In contrast to the findings with 100 mg M o.d., 10 mg bisoprolol o.d. guarantees a persistent reduction in exercise blood pressure and heart rate throughout the entire dosage interval of 24 h.
Assuntos
Pressão Sanguínea/efeitos dos fármacos , Teste de Esforço , Frequência Cardíaca/efeitos dos fármacos , Hipertensão/fisiopatologia , Metoprolol/uso terapêutico , Propanolaminas/uso terapêutico , Adolescente , Adulto , Idoso , Bisoprolol , Ensaios Clínicos como Assunto , Método Duplo-Cego , Feminino , Humanos , Hipertensão/tratamento farmacológico , Masculino , Metoprolol/efeitos adversos , Pessoa de Meia-Idade , Propanolaminas/efeitos adversos , Distribuição Aleatória , Descanso , Fatores de TempoRESUMO
A randomized, placebo-controlled, double-blind crossover investigation in 12 patients with non-asthmatic chronic obstructive lung disease and co-existing stable angina pectoris was done to compare two beta 1-selective adrenoceptor blocking agents, atenolol 100 mg and bisoprolol 20 mg. Systolic and diastolic blood pressures (SBP, DBP), heart rate (HR) as well as airway resistance (AWR, and less frequently forced expiratory volume in 1 s (FEV1) and intrathoracic gas volume (ITGV) were measured in the sitting position before and at various times up to 24 h after drug intake. During the first 4 h both beta-blockers produced a significant reduction in HR in comparison to placebo (p less than 0.01). Atenolol 100 mg significantly increased AWR relative to placebo and bisoprolol (p less than 0.05). After 24 h, a significant reduction in HR (p less than 0.01) could only be demonstrated after bisoprolol, whereas atenolol alone led to a significant elevation in AWR relative to placebo and bisoprolol (p less than 0.05) at that time. It is concluded that bisoprolol appears to have a high degree of beta 1-selectivity, thus providing a wide split between beta 1- and beta 2-adrenoceptor blockade. Bisoprolol in its therapeutic dose range is expected to be relatively safe as regards bronchoconstriction in patients suffering both from hypertension and/or angina pectoris and chronic obstructive lung disease.
Assuntos
Antagonistas Adrenérgicos beta/uso terapêutico , Angina Pectoris/fisiopatologia , Atenolol/uso terapêutico , Pneumopatias Obstrutivas/tratamento farmacológico , Propanolaminas/uso terapêutico , Adulto , Resistência das Vias Respiratórias/efeitos dos fármacos , Angina Pectoris/complicações , Bisoprolol , Método Duplo-Cego , Feminino , Hemodinâmica/efeitos dos fármacos , Humanos , Pneumopatias Obstrutivas/complicações , Masculino , Pessoa de Meia-Idade , Distribuição AleatóriaRESUMO
Liver damage is one of the most common organ manifestations of chronic alcoholism. The recovery process following abstinence should not be impaired by therapy with alcohol sensitizing drugs. In a double-blind multicentre-study (controlled against placebo) the liver tolerance of Nitrefazole which is indicated as an alcohol sensitizing agent for therapy of alcoholics, was tested during the first four weeks of a planned longterm therapy. A total of 62 patients with alcoholic liver disease--demonstrated clinically and in the laboratory--were tested. The patients received 800 mg of Nitrefazole (4 capsules a 200 mg), respectively 4 placebo capsules of identical appearance, once a week in the presence of the doctor. In both treatment groups there was a significant (p less than or equal to 0.01) decline of the previously pathologically altered laboratory values, especially concerning gamma-GT, GPT, GOT. The physical and mental condition which was additionally evaluated by the doctor improved within both treatment groups. The improvement of the liver functions due to abstinence is not delayed or impaired by Nitrefazole .
Assuntos
Hepatopatias Alcoólicas/tratamento farmacológico , Nitroimidazóis/farmacologia , Adulto , Idoso , Alcoolismo/tratamento farmacológico , Aspartato Aminotransferases/sangue , Método Duplo-Cego , Tolerância a Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , gama-Glutamiltransferase/sangueRESUMO
We entered 174 patients with healed duodenal ulcer and 77 with healed gastric ulcer into a double-blind, placebo-controlled, 6-month trial to investigate the efficacy of 1 g sucralfate twice daily in preventing ulcer recurrence. Endoscopy was performed after 6 months or earlier for symptoms compatible with ulcer disease. The relapse rate in the 126 patients with duodenal ulcer who could be evaluated for efficacy was 14/66 (21.2%) under sucralfate and 30/60 (50%) under placebo treatment (p less than 0.01). No significant difference in relapse rate was found in the 55 gastric ulcer patients who could be evaluated; 11 of 30 (37%) relapsed on sucralfate and 11 of 25 (44%) relapsed on placebo. Among the duodenal ulcer patients in the placebo group, those who had been treated initially with H2-receptor blockers for acute ulcer had significantly more relapses than patients who had been treated with other drugs. The recurrence rate was independent of prior treatment in the sucralfate group. Duodenal ulcer patients with a history of multiple episodes of active ulcer disease had a significantly higher rate of relapse than patients with only a few previous episodes. Both treatments were well tolerated. Two patients in each treatment group complained of nausea and epigastric pain immediately after drug intake. No other drug-related symptoms were observed. We conclude that sucralfate is effective in the prophylaxis of duodenal ulcer. No significant effect was found in the prevention of gastric ulcer recurrence.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Alumínio/uso terapêutico , Antiulcerosos/uso terapêutico , Úlcera Péptica/prevenção & controle , Alumínio/efeitos adversos , Antiácidos/uso terapêutico , Antiulcerosos/efeitos adversos , Ensaios Clínicos como Assunto , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Fumar , Sucralfato , Fatores de TempoRESUMO
In 37 patients with suspected vasospastic angina diagnostic ergonovine testing was used as a method of analysing the efficacy of sublingual ISDN in comparison with sublingual and intracoronary nifedipine on coronary luminal diameter, left ventricular ejection fraction, aortic blood pressure, heart rate and left ventricular end-diastolic pressure. 10 mg of sublingual ISDN counteracted the ergonovine effects on left ventricular pump function and hemodynamics. The luminal diameter of the epicardial coronary arteries increased from 3.5 +/- 0.8 to 4.9 +/- 0.8 mm. 20 mg of sublingual nifedipine did not change the coronary luminal diameter within 8-10 minutes after the ergonovine test. After administration of 0.1 mg of nifedipine into the right and left coronary artery the luminal diameters increased in the same range as after sublingual ISDN. Whereas the aortic blood pressure decreased after intracoronary nifedipine from 170 +/- 23 to 153 +/- 27 mmHg with a concomitant increase in heart rate, no effect on the left ventricular pump function could be assessed. In the model of ergonovine testing ISDN has shown itself as a potent drug in releasing the ergonovine effects. Sublingual ISDN is as potent as intracoronary nifedipine in releasing the ergonovine-induced reduction of coronary luminal diameters and more potent in counteracting the ergonovine effects concerning the cardiac pump function.
Assuntos
Vasos Coronários/efeitos dos fármacos , Ergonovina , Dinitrato de Isossorbida/farmacologia , Nifedipino/farmacologia , Adulto , Idoso , Vasoespasmo Coronário/diagnóstico , Feminino , Hemodinâmica/efeitos dos fármacos , Humanos , Dinitrato de Isossorbida/administração & dosagem , Masculino , Pessoa de Meia-Idade , Nifedipino/administração & dosagemAssuntos
Angina Pectoris Variante/diagnóstico , Vasoespasmo Coronário/diagnóstico , Ergonovina , Dinitrato de Isossorbida/uso terapêutico , Nifedipino/uso terapêutico , Piridinas/uso terapêutico , Adulto , Idoso , Angina Pectoris Variante/tratamento farmacológico , Angiografia Coronária , Circulação Coronária/efeitos dos fármacos , Vasoespasmo Coronário/tratamento farmacológico , Feminino , Hemodinâmica/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
A dual channel long-term-Ecg monitoring system was used to investigate arrhythmias in 90 patients undergoing diagnostic coronary arteriography. There was no significant difference of ventricular arrhythmias during an observation period of 10 hours before and after cardiac catheterization. The incidence of ventricular premature beats (VPB) was significantly higher in coronary patients than in normal controls (normal coronary arteries and normal ventriculograms) or in a group of 24 healthy soldiers. In patients with coronary artery disease (CAD) the incidence of VPB's was 82 %. There was, however, no significant correlation between the severity of CAD and the number of VPB's although patients with 3-vessel disease showed a tendency to produce more extopic beats. In contrast, patients with generalized or regional left ventricular akinesis (systolic shortening less than 15 %) showed a significantly higher number of VPB's than patients with normal or hypokinetic ventricles. In addition the analysis of qualitative criteria of ventricular arrhythmias with regard to their prognostic significance following Lown's definition showed the same close correlation with ventricular dysfunction. In the group of patients with VPB's of high incidence and prognostic importance cardiac index and ejection fraction was significantly decreased and left ventricular enddiastolic pressure significantly elevated. In conclusion, coronary patients with left ventricular akinesis are prone not only to produce congestive heart failure, but also life-threatening ventricular arrhythmias.