RESUMO
Tuberous sclerosis complex (TSC) is a genetic and systemic disorder characterized by benign hamartomatous tumors that involve multiple organ systems. The classical clinical triad of TSC consists of seizure, adenoma sebaceum (facial angiofibromata) and mental retardation. Renal angiomyolipomas are documented in approximately 40 - 80% of tuberous sclerosis patients and usually are small and asymptomatic. Less frequently nodules are large and lead to retroperitoneal hemorrhage. In these cases diagnosis can be difficult but definitive only after the histological examination or the systemic investigation of other possible tissue involvements. We describe the case of a 28 year old woman who came to the emergency department with acute postprandial abdominal pain and severe anemia due to hemorrhagic renal angiomyolipoma treated by nephrectomy in whom the following examination led to the diagnosis of TSC.
Assuntos
Angiomiolipoma/complicações , Hemorragia/etiologia , Neoplasias Renais/complicações , Espaço Retroperitoneal , Esclerose Tuberosa/complicações , Adulto , Angiomiolipoma/diagnóstico , Angiomiolipoma/cirurgia , Diagnóstico Diferencial , Feminino , Hemorragia/diagnóstico , Hemorragia/cirurgia , Humanos , Neoplasias Renais/diagnóstico , Neoplasias Renais/cirurgia , Nefrectomia , Espaço Retroperitoneal/irrigação sanguínea , Ruptura Espontânea , Esclerose Tuberosa/diagnósticoRESUMO
OBJECTIVE: The aim of our study was to assess the role of Doppler ultrasonography (DU) by resistive index (RI) and the difference of the RI (DeltaRI) in patients with acute unilateral renal obstruction. PATIENTS AND METHODS: We studied 36 consecutive patients (12 female, 24 male; mean age 45.6 +/- 8.4 years) with suspected renal colic by intravenous pyelography (IVP) and DU with determination of the RI and the Delta RI. A RI of >= 0.70 and a DeltaRI of >= 0.06 were considered suggestive of obstruction. IVP was considered as the "gold standard". RESULTS: In the studied population, RI was 0.664 +/- 0.060 in the affected kidney site of symptoms and 0.614 +/- 0.025 in the contralateral one, with an overall Delta RI of 0.049 +/- 0.062. At IVP, 14 patients resulted within normal range (Group A; 39%), 6 patients showed lithiasis without obstruction (Group B; 17%), 8 patients showed delayed excretion of the contrast medium (Group C; 22%), and 8 patients showed a functional exclusion of the kidney (Group D; 22%). One-way analysis of variance showed the IVP group significantly related to Delta RI with the highest values in Groups C (DeltaRI of 0.093 +/- 0.051; p<0.001) and D (DeltaRI of 0.116 +/-0.030; p<0.001) in comparison with Group A (DeltaRI of 0.001 +/-0.038) and Group B (DeltaRI of 0.015 +/-0.024). No differences were detected between Groups C and D (p=0.223) and between Groups A and B (p-0.472). DeltaRI measurement with DU permitted to predict the renal obstruction with a sensitivity of 93.8%, a specificity of 95.0% and an accuracy of 94.4%. CONCLUSIONS: Intrarenal Doppler ultrasonography represents a sensitive and highly specific test that can significantly contribute to the diagnosis of obstruction in patients with acute renal colic. It should be used as the first line imaging method in suspected acute renal colic, as well as for patients with renal insufficiency, pregnant women or for patients with adverse reactions to contrast media
Assuntos
Cólica/diagnóstico por imagem , Nefropatias/diagnóstico por imagem , Obstrução Ureteral/diagnóstico por imagem , Doença Aguda , Adulto , Velocidade do Fluxo Sanguíneo , Cólica/etiologia , Cólica/fisiopatologia , Feminino , Humanos , Nefropatias/etiologia , Nefropatias/fisiopatologia , Masculino , Valor Preditivo dos Testes , Circulação Renal , Reprodutibilidade dos Testes , Ultrassonografia Doppler/métodos , Cálculos Ureterais/complicações , Cálculos Ureterais/diagnóstico por imagem , Cálculos Ureterais/fisiopatologia , Obstrução Ureteral/etiologia , Obstrução Ureteral/fisiopatologia , Urografia/métodosRESUMO
AIMS/INTRODUCTION: The TOlerabilidad de LERcanidipino 20 mg frente a Amlodipino y Nifedipino en CondicionEs normales de uso study was aimed to compare the tolerability of high doses of lercanidipine with amlodipine and nifedipine gastro-intestinal therapeutic system (GITS) in the treatment of hypertension in daily clinical practice. PATIENTS/METHODS: Essential hypertensives >or= 18 years, treated during at least 1 month with lercanidipine 20 mg, amlodipine 10 mg or nifedipine GITS 60 mg, after a previous treatment course of at least 1 month with half the dose of the corresponding drugs were included. We present the data of the subgroup of patients with metabolic syndrome (MetS). RESULTS: Three hundred and thirty-seven of the 650 study population fulfilled criteria of MetS, 233 (69.1%) on lercanidipine and 104 (30.9%) on amlodipine/nifedipine GITS. Overall, a significantly lower proportion of lercanidipine-treated patients showed adverse reactions (ARs) when compared with patients receiving other-dihydropyridines (DHPs) (60.1% vs. 73.1%, p = 0.003). Similarly, the most common vasodilation-related ARs (oedema, swelling, flushing and headache) were significantly less frequent in lercanidipine group (all p < 0.01). CONCLUSION: In conclusion, lercanidipine appears to exhibit a better tolerability profile and less vasodilation-related ARs compared with other DHPs in hypertensive patients with MetS.
Assuntos
Anti-Hipertensivos/administração & dosagem , Di-Hidropiridinas/administração & dosagem , Hipertensão/tratamento farmacológico , Síndrome Metabólica/tratamento farmacológico , Adolescente , Adulto , Idoso , Anlodipino/efeitos adversos , Anlodipino/uso terapêutico , Anti-Hipertensivos/efeitos adversos , Bloqueadores dos Canais de Cálcio/efeitos adversos , Bloqueadores dos Canais de Cálcio/uso terapêutico , Estudos Transversais , Di-Hidropiridinas/efeitos adversos , Relação Dose-Resposta a Droga , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nifedipino/efeitos adversos , Nifedipino/uso terapêuticoRESUMO
OBJECTIVES: To determine the clinical characteristics and management of patients with non-valvular atrial fibrillation (NVAF) treated with direct oral anticoagulants (DOAC) according to who initiates their prescription, the Primary Care (PC) physician or referring the patient to a specialist. MATERIAL AND METHODS: Two observational, cross-sectional and multicentre studies were compared for this purpose. The SILVER-AP study was performed in those autonomous communities in which the PC physician can prescribe DOAC directly, and the BRONCE-AP study in those autonomous communities in which the PC physician has to refer the patient to the specialist to start treatment with DOAC. Patients on chronic treatment with anticoagulants, in whom therapy was changed, and those that were on current treatment with DOAC for at least 3months, were included. RESULTS: A total of 1,036 patients (790 from SILVER-AP study and 246 from BRONCE-AP study) were included. Compared with the BRONCE-AP study, those patients included in SILVER-AP were older and had more comorbidities, as well as a higher thromboembolic and haemorrhagic risk (CHA2DS2-VASc 4.3±1.6 vs. 3.8±1.8; P<.001; HAS-BLED 2.1±0.8 vs. 1.8±1.0; P<.001). Therapeutic adherence and satisfaction with treatment were high. Low doses of DOAC were frequently prescribed, particularly with dabigatran. CONCLUSIONS: Those patients in whom the PC physician can prescribe DOAC directly have a worse clinical profile, as well as a higher thromboembolic and haemorrhagic risk than those patients in whom the PC physician has to refer to the specialist.
Assuntos
Anticoagulantes/administração & dosagem , Fibrilação Atrial/tratamento farmacológico , Atenção Primária à Saúde/estatística & dados numéricos , Especialização/estatística & dados numéricos , Administração Oral , Adulto , Estudos Transversais , Relação Dose-Resposta a Droga , Feminino , Hemorragia/epidemiologia , Humanos , Masculino , Adesão à Medicação/estatística & dados numéricos , Pessoa de Meia-Idade , Satisfação do Paciente/estatística & dados numéricos , Padrões de Prática Médica/estatística & dados numéricos , Encaminhamento e Consulta , Tromboembolia/epidemiologiaRESUMO
OBJECTIVE: To determine the clinical characteristics and management of hypertensive patients with nonvalvular atrial fibrillation (AF) treated with direct oral anticoagulants (DOACs) according to blood pressure (BP) control. METHODS: For this purpose, data from two observational, cross-sectional and multicenter studies were combined. In both studies, patients on chronic treatment with anticoagulants and that were on current treatment with DOACs at least for 3 months were included. Adequate BP was defined as a systolic BP<140mmHg and a diastolic BP<90mmHg (<140/85mmHg if diabetes). RESULTS: Overall, 1036 patients were included. Of these, 881 (85%) had hypertension that were finally analyzed. The presence of other risk factors and cardiovascular disease was common. Mean BP was 132.6±14.3/75.2±9.2mmHg and 70.5% of patients achieved BP goals. Those patients with a poor BP control had more frequently diabetes, and a history of prior labile INR. Patients had a high thromboembolic risk, but without significant differences according to BP control. By contrast, more patients with a poor BP control had a higher bleeding risk (HAS-BLED ≥3: 24.0% vs 35.4%; P<0.001). HAS-BLED score was an independent predictor of poor BP control (odds ratio 1.435; 95% confidence interval 1.216-1.693; P<0.001). Satisfaction with anticoagulant treatment was independent of BP control. CONCLUSIONS: More than two thirds of our patients with hypertension and AF anticoagulated with DOACs achieve BP targets, what is clearly superior to that reported in the general hypertensive population.
Assuntos
Fibrilação Atrial/complicações , Pressão Sanguínea/efeitos dos fármacos , Inibidores do Fator Xa/uso terapêutico , Hipertensão/complicações , Trombofilia/tratamento farmacológico , Administração Oral , Idoso , Idoso de 80 Anos ou mais , Fibrilação Atrial/fisiopatologia , Estudos Transversais , Complicações do Diabetes/fisiopatologia , Gerenciamento Clínico , Dislipidemias/complicações , Inibidores do Fator Xa/farmacologia , Feminino , Humanos , Hipertensão/fisiopatologia , Masculino , Estudos Multicêntricos como Assunto/estatística & dados numéricos , Estudos Observacionais como Assunto/estatística & dados numéricos , Satisfação do Paciente , Acidente Vascular Cerebral/prevenção & controle , Trombofilia/etiologiaRESUMO
The pituitary gland can be involved in a variety of medical conditions, including metastatic tumors. Metastases to the pituitary gland, although absolutely rare, more commonly affect the posterior pituitary lobe and so frequently present with diabetes insipidus. We report on a 48-year-old male heavy smoker patient suffering from sudden onset of polyuria and persistent thirst. Laboratory results revealed central diabetes insipidus. Computed tomography (CT) scan of the brain showed a mass located in the sella turcica and in the suprasellar region. CT scan of the chest showed a mass in the right superior lobe with mediastinal lymphadenopathy, with bronchoscopy and biopsy features of pulmonary adenocarcinoma. The patient received radiotherapy on the pituitary gland and adjuvant chemotherapy, and as intrasellar and suprasellar mass decreased in size, urinary output was accordingly reduced. Therefore, is that in patients with risk factors for cancer and sudden onset of diabetes insipidus pituitary metastasis should be taken into account in differential diagnosis.
Assuntos
Adenocarcinoma/secundário , Diabetes Insípido Neurogênico/etiologia , Hemianopsia/etiologia , Neoplasias Pulmonares/patologia , Neoplasias Hipofisárias/secundário , Poliúria/etiologia , Fumar/efeitos adversos , Adenocarcinoma/complicações , Diabetes Insípido Neurogênico/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Hipofisárias/complicações , Sela TúrcicaRESUMO
This cross-sectional, multicenter study investigated the prevalence of chronic kidney disease and associated disorders, in an adult population sample (> 18 years old) attending Primary Care services in Spain. Estimated glomerular filtration rate (Modification Diet in Renal Disease equation) was used for analysis of kidney disease prevalence according to NFK-KDOQI (The National Kidney Foundation-Kidney Disease Outcomes Quality Initiative) stages. Data were collected on serum creatinine, other laboratory parameters blood pressure, and medical history of cardiovascular risk factors or disease (hypertension, dislypidemia, diabetes, congestive heart failure, coronary artery disease, stroke or peripheral arteriopathy) in 7,202 patients attending Primary Care Centers. 47.3% were males, mean age 60,6 +/- 14,3 years, BMI 28.2 +/- 5.3, with 27,6% overweight (27-30 kg/m2) and 32,1% obese (BMI>or=30 kg/m2), The prevalence of cardiovascular risks factors were: absence in 17.3%, one factor 26.9% two 31.2%, and 23.6% presented three or more The frequency of CV risk factors was: hypertension (66.7%), dyslipidemia (48%) and diabetes (31.5%). Congestive heart failure, coronary artery disease, stroke or peripheral vascular disease frequency was lower than 10% The prevalence of eGFR < 60 ml/min x 1.73 m2 was: stage 3 (30-59 ml/min/1.73 m2) 19.7%; stage 4 (15-29 ml/min/1.73 m2) 1.2%; stage 5 no dialysis (GFR < 15 ml/min) 0.4%. This prevalence increased with age in both sexes and 33,7% of patients attending Primary Care services over 70 years presented a eGFR < 60 ml/min. Of the total patients with eGFR < 60 ml/min 37.3% had normal serum creatinine levels. This study documents the substantial prevalence of significantly abnormal renal function among patients at Primary Care level. Early identification and appropriate nephrological management of these patients with renal disease is an important opportunity for an adequate prescription of drugs that interfere with renal function, to delay the progression of renal disease and modify CV risk factors.
Assuntos
Insuficiência Renal Crônica/epidemiologia , Adulto , Idoso , Doenças Cardiovasculares/epidemiologia , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Atenção Primária à Saúde/estatística & dados numéricos , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/prevenção & controle , Fatores de Risco , Espanha/epidemiologiaRESUMO
Cannulation of central veins and placement of catheters for temporary haemodialysis is a common procedure in the management of patients with end stage renal failure. The internal jugular vein is the site of choice for central venous catheter placement, being associated with the lowest complication rate. This procedure can be associated with a variety of malpositions of the catheter and rarely, can lead to significant morbidity and even mortality, if this is not recognised and corrected early. For anatomical reasons, the risk of azygos arch cannulation is substantially increased if catheters are inserted via left-sided veins. We report a case with a rare complication associated with the insertion of a catheter for temporary haemodialysis.
Assuntos
Veia Ázigos/diagnóstico por imagem , Cateterismo Venoso Central/efeitos adversos , Diálise Renal , Feminino , Humanos , Veias Jugulares/diagnóstico por imagem , Pessoa de Meia-Idade , Diálise Renal/métodos , Tomografia Computadorizada por Raios XRESUMO
A Phase I study of angiogenesis inhibitor TNP-470 was conducted in patients with advanced cancer. TNP-470 (25-235 mg/m2) was administered i.v. over 4 h once a week to patients who had solid tumors refractory to the best available treatment or with a high risk of recurrence and who had normal renal, hepatic, and hematological function and no evidence of coagulopathy. The aims of the study were to determine the maximum tolerated dose, dose-limiting toxicities (DLTs), and the pharmacokinetics of TNP-470 given on a once-weekly schedule. Thirty-six patients, ages 23-75 (median, 54 years), with an Eastern Cooperative Oncology Group performance status of 0-2 were treated. The number of patients at each dose level (mg/m2) were 6 (25), 3 (50), 3 (75), 3 (100), 3 (133), 12 (177), and 6 (235). The principal toxicities of TNP-470 were dizziness, lightheadedness, vertigo, ataxia, decrease in concentration and short-term memory, confusion, anxiety, and depression, which occurred at doses of 133, 177, and 235 mg/m2. Two patients treated at 235 mg/m2 experienced DLT in the form of grade III cerebellar neurotoxicity after 6 weeks of treatment. Overall, these neurological symptoms were dose-related, had an insidious onset, progressively worsened with treatment, and resolved completely within 2 weeks of stopping the drug. One patient with malignant melanoma had stabilization of the previously growing disease for 27 weeks while on the treatment. Two patients, one with adenocarcinoma of the colon and the other with a soft tissue sarcoma, had no clinically detectable disease but were at high risk for recurrence at the initiation of treatment and received 13 months and > 3 years of treatment, respectively, with no evidence of disease recurrence. The remaining patients had progression of their disease after 1-6 months of treatment. The mean plasma half-life (t(1/2)) of TNP-470 and its principal metabolite, AGM-1883, were extremely short (harmonic mean, t(1/2) of 2 and 6 min, respectively) with practically no drug detectable in the plasma by 60 min after the end of the infusion. MII, an inactive metabolite, had a considerably longer t(1/2) of approximately 2.6 h. Mean peak TNP-470 concentrations were > or = 400 ng/ml at doses > or = 177 mg/m2. On the basis of this study, the maximum tolerated dose of TNP-470 administered on a weekly schedule was 177 mg/m2 given i.v over 4 h. The principal DLT was neurotoxicity, which appeared to be dose-related and was completely reversible. On the basis of the short plasma t(1/2) of TNP-470, exploration of a prolonged i.v. infusion schedule is warranted.
Assuntos
Antibióticos Antineoplásicos/administração & dosagem , Antibióticos Antineoplásicos/farmacocinética , Neoplasias/tratamento farmacológico , Neovascularização Patológica/tratamento farmacológico , Sesquiterpenos/administração & dosagem , Sesquiterpenos/farmacocinética , Adulto , Idoso , Antibióticos Antineoplásicos/efeitos adversos , Antibióticos Antineoplásicos/sangue , Sistema Nervoso Central/efeitos dos fármacos , Ataxia Cerebelar/induzido quimicamente , Confusão/induzido quimicamente , Cicloexanos , Relação Dose-Resposta a Droga , Avaliação de Medicamentos , Feminino , Humanos , Masculino , Memória/efeitos dos fármacos , Pessoa de Meia-Idade , Neoplasias/irrigação sanguínea , O-(Cloroacetilcarbamoil)fumagilol , Sesquiterpenos/efeitos adversos , Sesquiterpenos/sangue , Vertigem/induzido quimicamenteRESUMO
Docetaxel and gemcitabine have been shown to be active as single agents in a variety of solid tumors. These two agents have been studied in combination with several different treatment schedules. Two phase I studies used a novel 2-week administration schedule that involved a 1-hour infusion of 35 mg/m2 to 65 mg/m2 docetaxel and gemcitabine administered as either a 30-minute infusion (2,000 to 4,000 mg/m2) or a 10 mg/m2/min infusion (1,000 to 1,200 mg/m2 total dose). Another novel phase I study evaluated the effect of drug sequence on toxicities. Patients received 30 to 40 mg/m2 docetaxel and 800 to 1,250 mg/m2 gemcitabine on days 1 and 8 every 21 days. Two phase I studies of a monthly docetaxel regimen have been conducted. Patients received 800 mg/m2 gemcitabine on days 1, 8, and 15 and 100 mg/m2 docetaxel on day 1 of a 28-day cycle. Finally, in a phase II study, patients received 900 mg/m2 gemcitabine on days 1 and 8 and 100 mg/m2 docetaxel on day 8, with granulocyte colony-stimulating factor administered on days 9 through 15. In these studies, antitumor responses were observed in lung cancer as well as a number of other histologies. Neutropenia was the most frequent dose-limiting toxicity and no difference in clinical toxicity was observed with either sequence of administration. The emerging evidence suggests, therefore, that the combination of gemcitabine and docetaxel is active in a variety of solid tumors and is well tolerated.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Taxoides , Ensaios Clínicos Fase I como Assunto , Ensaios Clínicos Fase II como Assunto , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Docetaxel , Humanos , Paclitaxel/administração & dosagem , Paclitaxel/análogos & derivados , GencitabinaRESUMO
The binding of human plasminogen and plasmin to the promastigote form of Leishmania mexicana was investigated. L. mexicana was capable to bind both molecules, the binding being inhibited by epsilon-aminocaproic acid. Scatchard plot analysis revealed a dissociation constant (Kd) value of 2.4+/-0.8 microM and 0.9+/-0.1 x 10(4) binding sites per cell for plasminogen and a Kd value of 1.2+/-0.4 microM and 1.6+/-0.2 x 10(5) binding sites per cell for plasmin. C-terminal lysine residues are involved in plasminogen binding to cells, since carboxypeptidase B treatment reduced this binding by 34%. Ligand blotting analysis showed a group of proteins, with molecular masses between 105 and 115 kDa, capable to interact with plasminogen. Zymogram analysis showed that the protease activity acquired by L. mexicana, due to the interaction with either plasminogen or plasmin, comprises an important fraction of the total protease activity at pH 7.7. Plasminogen activation by tissue-type plasminogen activator (t-PA) was enhanced by the presence of L. mexicana promastigotes. These results raise the question whether the interaction of L. mexicana with components of the fibrinolytic system is involved in the virulence of the parasite.
Assuntos
Fibrinolisina/metabolismo , Leishmania mexicana/metabolismo , Plasminogênio/metabolismo , Animais , Carboxipeptidases/metabolismo , Humanos , Immunoblotting , Leishmania mexicana/crescimento & desenvolvimento , Peptídeo Hidrolases/metabolismo , Ligação Proteica , Proteínas de Protozoários/metabolismo , Ativador de Plasminogênio Tecidual/metabolismo , Ativador de Plasminogênio Tipo Uroquinase/metabolismoRESUMO
BACKGROUND: The prevalence of echocardiographic left ventricular hypertrophy in essential hypertension ranges from 12 to 96% depending on the threshold values used to define it, and on the selection bias. OBJECTIVE: To estimate the prevalence of echocardiographic left ventricular hypertrophy by different criteria in essential hypertensives seen in primary care centres. METHODS: Cross-sectional study in a population-based sample of 946 essential hypertensives randomly selected in 39 primary care centres across Spain. Echocardiographic studies were performed in reference hospitals by trained observers (concordance Cohen kappa index > 0.7) and analysed by a single observer. RESULTS: Prevalence of left ventricular hypertrophy ranged from 59.2% [95% confidence interval (CI) 56.1 -62.3] by Framingham criteria to 72.7% (95% CI 69.9-75.6) using the criteria of De Simone et al. (J Am Coll Cardiol 1995; 25: 1056-1062). Prevalence was higher in males by the Cornell-Penn criteria, but higher in females when using Framingham or De Simone et al. criteria. Eccentric hypertrophy was more frequent (51.3-54.1%) independently of the criteria used, particularly when adjusting wall-thickness-ratio for age (56.2-58.9%). Concentric remodelling was present in 6.5-11.4% and only 20.8-29.7% of patients had no evidence of left ventricular structural alterations. Factors independently associated with left ventricular hypertrophy in the logistic regression analysis were age, gender, systolic blood pressure, pulse pressure and body mass index. CONCLUSION: Prevalence of echo left ventricular structural alterations among essential hypertensives seen in primary care centres in Spain ranged from 70.3 to 79.2% depending on the threshold values used. Left ventricular hypertrophy ranged from 59.2 to 72.7% and age-adjusted concentric remodelling ranged from 6.5 to 11.4% depending on the criteria used. Only one-quarter of hypertensive patients were free from morphological alterations.
Assuntos
Hipertensão/complicações , Hipertrofia Ventricular Esquerda/diagnóstico , Hipertrofia Ventricular Esquerda/etiologia , Idoso , Estudos Transversais , Feminino , Humanos , Hipertensão/fisiopatologia , Hipertrofia Ventricular Esquerda/fisiopatologia , Masculino , Pessoa de Meia-Idade , PrevalênciaRESUMO
OBJECTIVE: To compare the anti-hypertensive effect of combination therapy versus a single drug regimen schedule (dose-titration or switching to a different drug class) in type 2 diabetic hypertensive patients with inadequate blood pressure (BP) control on monotherapy. DESIGN: Prospective, randomized, open-fashion, parallel study of two therapeutic strategies during an 8-week period. SETTING: Primary care centers in Spain. PARTICIPANTS: A total of 898 men and women with type 2 diabetes mellitus and hypertension, receiving antihypertensive treatment with one single drug and whose BP was > 140 and/or 90 mmHg. INTERVENTION: Patients were randomized to a fixed combination therapy (verapamil 180 mg plus trandolapril 2 mg; Knoll AG, Ludwigshafen, Germany) or continued on a single drug regimen, either increasing the dose of the current drug or switching to a different drug class. MAIN OUTCOME MEASURE: Absolute BP reduction in the two groups of treatment, and the percentage of normalized patients (< 140/90 mmHg) in each group. RESULTS: The diastolic BP (DBP) decrease (5.6 mmHg) was significantly greater in patients treated with combination therapy, compared to patients on monotherapy (2.9 mmHg). The decrease in systolic BP (SBP) was not significantly different (11.1 versus 10.0 mmHg). In addition, a significantly higher number of patients treated with combination therapy (82% versus 74%) reached diastolic BP normalization (< 90 mmHg). CONCLUSIONS: In type 2 hypertensive patients with uncontrolled BP despite anti-hypertensive monotherapy, the change to combination therapy was more effective in attaining DBP control than any monotherapy schedule (either increasing the dose or switching to another different drug class).
Assuntos
Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Atitude Frente a Saúde , Bloqueadores dos Canais de Cálcio/uso terapêutico , Angiopatias Diabéticas/tratamento farmacológico , Angiopatias Diabéticas/psicologia , Hipertensão/tratamento farmacológico , Hipertensão/psicologia , Indóis/uso terapêutico , Verapamil/uso terapêutico , Idoso , Pressão Sanguínea/efeitos dos fármacos , Diabetes Mellitus Tipo 2 , Angiopatias Diabéticas/fisiopatologia , Diástole , Quimioterapia Combinada , Feminino , Humanos , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
PURPOSE: To determine the maximum tolerated dose (MTD), dose-limiting toxicity (DLT), and effect of drug sequence on toxicities and pharmacokinetics of the combination of gemcitabine and docetaxel. METHODS: A total of 34 patients with advanced cancers were treated with gemcitabine and docetaxel on days 1 and 8 of each 21-day cycle according to the following dose escalation schedule: level 1, 800 and 30 mg/m2, respectively; level 2, 800 and 40 mg/m2; level 3, 1,000 and 40 mg/m2; and level 4, 1,250 and 40 mg/m2. At each dose level, at least three patients were assigned to one of the two sequences of drug administration: gemcitabine-->docetaxel or docetaxel-->gemcitabine. Once the MTD had been reached, six additional patients, who had received no more than one chemotherapy regimen, were enrolled to dose levels 3 and 4 (gemcitabine-->docetaxel) to determine the MTD in minimally pretreated patients. RESULTS: Neutropenia was the most frequent DLT with an overall incidence of 23.5%. Grade 3/4 neutropenia occurred in 62% of patients (8/13) who had received two or more prior chemotherapy regimens, but not at all (0/15) in patients who had received no more than one prior chemotherapy regimens (P< 0.001). Additional DLTs included grade 4 diarrhea and grade 4 stomatitis in one patient each. The MTD was determined to be gemcitabine 800 mg/m2 and docetaxel 40 mg/m2 in patients who had received two or more prior chemotherapy regimens. However, minimally pretreated patients (no more than one prior chemotherapy regimen) were able to tolerate higher doses with an MTD of gemcitabine 1,250 mg/m2 and docetaxel 40 mg/m2. There were no significant differences in toxicities or pharmacokinetics between the two sequences of administration. Partial and minor responses were observed in 23.5% of patients: non-small-cell lung (two of eight), gastric (two of three), head and neck (one of two), bladder (two of four) and hepatocellular cancer (one of one). CONCLUSIONS: The combination of gemcitabine and docetaxel administered on days 1 and 8 every 21 days was feasible and well tolerated in patients with advanced malignancies. The sequence of administration had no significant effect on the toxicity or pharmacokinetics of either drug. Minimally pretreated patients tolerated higher doses of this combination without significant toxicities. This schedule and combination demonstrated activity in a variety of solid tumors, and merits further evaluation.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/farmacocinética , Neoplasias/metabolismo , Taxoides , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Desoxicitidina/farmacocinética , Docetaxel , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/tratamento farmacológico , Paclitaxel/administração & dosagem , Paclitaxel/análogos & derivados , Paclitaxel/farmacocinética , GencitabinaRESUMO
To study how changes in dietary salt influence the blood pressure (BP) of pharmacologically controlled hypertensive patients, we have selected from a large multicenter trial two subgroups of 14 and 16 patients who attained BP control (office DBP < 90 mm Hg) after a 4-week treatment with verapamil SR 240 mg once daily, either under an unrestricted salt diet (high-salt; 14 patients) or under a moderately restricted salt diet (low-salt; 16 patients). All of them were switched to the opposite dietary salt regimen and continued on verapamil for 4 more weeks (Salt-Switching-Period). Office BP and ambulatory blood pressure monitoring (ABPM) were registered before and after the Salt-Switching-Period. Salt intake was checked by urinary sodium excretion (UNa). Patients switching from high- to low-salt reduced UNa from 180.9 +/- 22.9 to 89 +/- 28 mM Na/24h (P < 0.001) and patients switching from low- to high-salt increased UNa from 85 +/- 38.4 to 175.8 +/- 57.5 mM Na/24h (P < 0.001). No significant changes in BP were found by ABPM either in the group switching from high- to low-salt or in the group switching from low- to high-salt. In the latter group, a significant increase was observed in office DPB but not in SBP. Short-term changes in salt intake seem to have little influence on the BP of patients pharmacologically controlled with verapamil.
Assuntos
Dieta Hipossódica , Hipertensão/dietoterapia , Hipertensão/tratamento farmacológico , Verapamil/uso terapêutico , Adulto , Idoso , Análise de Variância , Pressão Sanguínea/efeitos dos fármacos , Monitorização Ambulatorial da Pressão Arterial , Estudos Cross-Over , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sódio/metabolismo , Verapamil/administração & dosagemRESUMO
The aim of this study was to determine concordance between physician and patient blood pressure (BP) measurements in an ambulatory setting. A diagnostic intervention cross-sectional study using a convenience sample was employed. A total of 106 hypertensive patients were included in the study. Patients who were unable to perform their self-measurement or those with cardiac arrhythmia were excluded. BP was determined nine times in each subject in the medical office in a randomised order: BP was taken three times by the physician using a mercury sphygmomanometer (SPH-Hg), three times by the physician using a validated, automated oscillometer (Omron HEM 705 CP), and three times by the patient himself with the same device. The intraclass correlation coefficient was calculated. In all, 59 women and 47 men aged 65.7 (10) years were analysed. Mean BP measurements for the physician using the mercury sphygmomanometer, the physician using the Omron, and the patient using the same device were: 136 (15.8)/80 (11), 137 (17.9)/80 (10), and 139* (17.6)/80 (10) mmHg, respectively. BP control was 48.1, 48.1, and 36.8*% (*P < 0.05), respectively. Intraclass correlation coefficients for systolic/diastolic pressures were: 0.77/0.65 (physician-sphygmomanometer Hg, physician-Omron; P < 0.001), 0.75/0.64 (physician-sphygmomanometer Hg, patient-Omron, P < 0.001), and 0.83/0.83 (physician-Omron, patient-Omron; P < 0.001). In conclusion, the three types of measurement in the medical office were significantly concordant. Patient office self-measurement showed a tendency to increase systolic BP and worsen BP control.
Assuntos
Determinação da Pressão Arterial/métodos , Hipertensão/diagnóstico , Esfigmomanômetros , Monitorização Ambulatorial da Pressão Arterial/métodos , Estudos Transversais , Feminino , Humanos , Masculino , Relações Médico-Paciente , Probabilidade , Estudos de Amostragem , Autoexame , Sensibilidade e EspecificidadeRESUMO
Some meta-analyses have suggested that the selective serotonin reuptake inhibitors (SSRIs) are less effective than clomipramine in the treatment of obsessive-compulsive disorder (OCD). The aim of this double-blind, randomised, multicentre study was to directly compare the efficacy and safety of fluvoxamine and clomipramine in patients with OCD. A total of 227 patients were randomised to flexible doses of fluvoxamine or clomipramine (both 150-300 mg/day) for 10 weeks. Fluvoxamine and clomipramine were both clinically effective and there were no statistically significant differences between the two treatment groups, at any visit, on the National Institute of Mental Health Obsessive-Compulsive global rating scale, the Yale-Brown Obsessive-Compulsive scale (total score and obsession and compulsion subscores), the Clinical Global Impression severity of illness and global improvement subscales, the Clinical Anxiety Scale and the 17-item Hamilton Depression Rating Scale. However, there were differences in safety between the two treatments. Compared with fluvoxamine-treated patients, those treated with clomipramine had more anticholinergic side effects (dry mouth, constipation and tremor) and premature withdrawals due to adverse events (18 versus 9). The results from this controlled study indicate that fluvoxamine is as effective as clomipramine in the treatment of OCD but has a better tolerability profile. Copyright 2001 John Wiley & Sons, Ltd.
RESUMO
BACKGROUND: Achievement of a controlled blood pressure and improvement of cardiovascular risk profile are the mainstays of therapy for hypertension. OBJECTIVE: To assess the responses of heart rate and blood pressure in hypertensive patients to 240 mg/day sustained release verapamil. METHODS: We assessed the effect of 240 mg/day sustained released verapamil on blood pressure and heart rate, measured in the office and at home, in 1395 hypertensive outpatients with mild-to-moderate hypertension, who were using an Omron HEM 705 CP automatic device for self-measurement. The period of observation was 3 months. RESULTS: Blood pressure decreased both in the medical office and at the patient's home, the measurements obtained at home being lower than those found in the office. Heart rate decreased in a significant and particular way. The decrease was greatest among those patients with histories of myocardial infarction and among relatively young patients, who exhibit a tendency towards higher than normal baseline heart rates. Overall, there was a shift of the heart-rate curve towards more controlled levels clustered around heart rates between 65 and 75 beats/min. Home self-measurement showed that the data gathered by the patients at home are reliable and that, when cut-off values of 140/90 mm Hg for blood pressure are used, the percentage of patients with controlled blood pressures is 62%, whereas the percentage obtained in the medical office by the physician is 56%. If cut-off values of 135/85 mm Hg are considered for self-measurements at home, according to the VI JNC recommendations, the percentage of patients with controlled blood pressures is 25.4%.
Assuntos
Monitorização Ambulatorial da Pressão Arterial , Pressão Sanguínea/efeitos dos fármacos , Frequência Cardíaca/efeitos dos fármacos , Hipertensão/tratamento farmacológico , Autocuidado , Vasodilatadores/uso terapêutico , Verapamil/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Instituições de Assistência Ambulatorial , Preparações de Ação Retardada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Vasodilatadores/administração & dosagem , Verapamil/administração & dosagemRESUMO
BACKGROUND: White coat hypertension (WCH) is a relatively prevalent clinical situation (around 20% of the hypertense population). The aim of this study was to analyze the clinical characteristics of these patients. METHODS: A descriptive transversal study was carried out in general medicine consultations in a unrandomized sample of hypertensive patients receiving pharmacologic treatment. Twenty-four hour ambulatory blood pressure monitorization (ABPM) (SpaceLabs 90202-90207) was performed following three resting blood pressure (BP) determinations carried out during the visit at 5-minute intervals by mercury sphigmomanometer. WCH was defined as: BP during the consultation > 140 mmHg (systolic) or > 90 mmHg (diastolic) with a mean daily blood pressure by ABPM < 140/< 90 mmHg. RESULTS: One hundred sixty-four patients (53% males) with a mean age of 48 years (SD 15.8) and a mean time of high blood pressure of 36 months (SD 51.4) were studied. Seventy-one patients (43%) fulfilled WCH criteria. WCH was significantly associated with females (p < 0.01), hypercholesterolemia (p < 0.05), lower involvement of target organs (p < 0.05), greater nocturnal tolerance to ABPM (p < 0.05) and lower mean nocturnal blood pressure (p < 0.001). CONCLUSIONS: The prevalence of white coat hypertension is elevated. Most of these patients are females, have fewer target organ lesions that the remaining hypertensive patients although dyslipemia is more frequently observed in these cases.
Assuntos
Hipertensão/diagnóstico , Adulto , Determinação da Pressão Arterial , Estudos Transversais , Feminino , Humanos , Hipertensão/epidemiologia , Masculino , Pessoa de Meia-Idade , PrevalênciaRESUMO
BACKGROUND: There is poor information for isolated clinical tachycardia (ICT), that is to say, office tachycardia but normal ambulatory heart rate (HR). Our objective was to describe it and to know differences between hypertensive subjects with and without ICT. PATIENTS AND METHOD: Comparative study after a diagnostic intervention (ambulatory blood pressure monitoring, ABPM, SpaceLabs 90202-90207), with convenience sampling of non-treated hypertensive patients attended in primary care. We excluded subjects with heart, thyroid or lung disease. ICT were defined on the basis of office and daytime HR percentile 90 of the whole sample. RESULTS: A total of 256 subjects were included, 128 (50%) women, age 49.1 (16.1) years, with mean office blood pressure (BP) 151 (17.1)/92 (11.9) mmHg. The prevalence of ICT was 7.03% (CI 95%, 4.03-11.07) (n = 18). We didn't find any association between isolated clinical hypertension and ICT (p = 0.87). Patients with ICT have lower office and systolic night time BP, lower night time variability, higher night time BP fall, although higher 24 hours-HR and daytime-HR in comparison with non ICT hypertensive patients. In the multivariate analysis only office diastolic BP (OR, 0.93 [CI 95%, 0.87-0.98], for each mmHg increment) and office HR (OR, 1.2 [CI 95%, 1.11-1.28], for each beat for minute increment) were predictive of ICT. CONCLUSIONS: In this study 7.03% of non treated hypertensive patients present ICT, which suggest a profile of more favorable cardiovascular risk than that without ICT. Only office diastolic BP and office HR were predictive variables of ICT.