RESUMEN
BACKGROUND: The efficacy of infliximab in ulcerative colitis (UC) and indeterminate colitis has been poorly assessed and preliminary results are conflicting. METHODS: The records of 30 patients treated with infliximab for ulcerative colitis (n=19) or indeterminate colitis (n=11) were reviewed. Infliximab was given because of steroid resistance (n=18), dependence (n=5) or intolerance (n=7); five patients had failed on cyclosporin; 19 patients had a severe flare-up. RESULTS: Median duration of follow-up was 10 months. In 28 patients with active disease, the response rate was 75% at day 7, with 43% having a complete remission, and 50% at month 1, with 32% having a complete remission. Among the 22 responders, the probability of relapse was 73% at month 6. The probability of complete remission without steroids, taking into account the re-treatment for relapse (n=11), was 57% (95% confidence interval (CI): 45% to 69%) at month 6. The probability of colectomy was 33% (95% CI: 23% to 43%) at month 12. In indeterminate colitis, response rate was only 50% at day 7 and 30% at month 1. Concomitant use of antimetabolite agents was associated with better results. CONCLUSIONS: Infliximab was able to induce a rapid response in some patients with UC or indeterminate colitis refractory to conventional treatment. Long-term results were less favourable, with frequent relapses, and about one-third of the patients required a colectomy.
Asunto(s)
Anticuerpos Monoclonales/uso terapéutico , Colitis/tratamiento farmacológico , Fármacos Gastrointestinales/uso terapéutico , Adolescente , Adulto , Anciano , Enfermedad Crónica , Estudios de Cohortes , Colectomía , Colitis Ulcerosa/tratamiento farmacológico , Femenino , Humanos , Infliximab , Masculino , Persona de Mediana Edad , Recurrencia , Inducción de Remisión , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
We previously showed that chronic angiotensin-converting enzyme (ACE) inhibition prevented the increase in aortic collagen in spontaneously hypertensive rats (SHRs) independently of blood pressure reduction. The aim of the present study was to determine whether the effects of ACE inhibition on aortic fibrosis were due to inhibition of angiotensin II formation, preservation of bradykinin, or a combination of both. Four week-old SHRs were treated for 4 months with the ACE inhibitor quinapril, quinapril with the bradykinin B2 receptor antagonist Hoe 140, or the angiotensin II AT1 receptor antagonist CI996. Control SHR and Wistar-Kyoto (WKY) rats received a placebo for the same period of time. At the end of the treatment, as compared to conscious SHR and WKY controls, quinapril completely prevented the development of hypertension, whereas quinapril-Hoe 140 and the AT1 receptor antagonist produced only a partial reduction of blood pressure. In relation with blood pressure changes, aortic hypertrophy was significantly prevented by quinapril but not by quinapril-Hoe 140 or CI996. In contrast, aortic collagen accumulation was completely prevented by all three treatments. The study provides evidence that in young live SHRs, the prevention of aortic collagen accumulation is independent of blood pressure changes and bradykinin preservation and involves exclusively angiotensin II inhibition through AT1 receptors.
Asunto(s)
Angiotensina II/fisiología , Inhibidores de la Enzima Convertidora de Angiotensina/farmacología , Aorta Torácica/efectos de los fármacos , Bradiquinina/análogos & derivados , Bradiquinina/fisiología , Colágeno/metabolismo , Hipertensión/metabolismo , Imidazoles/farmacología , Isoquinolinas/farmacología , Tetrahidroisoquinolinas , Tetrazoles/farmacología , Angiotensina II/antagonistas & inhibidores , Antagonistas de Receptores de Angiotensina , Inhibidores de la Enzima Convertidora de Angiotensina/administración & dosificación , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Animales , Aorta Torácica/metabolismo , Aorta Torácica/patología , Bradiquinina/administración & dosificación , Bradiquinina/antagonistas & inhibidores , Bradiquinina/farmacología , Bradiquinina/uso terapéutico , Antagonistas de los Receptores de Bradiquinina , Quimioterapia Combinada , Hemodinámica/efectos de los fármacos , Hipertensión/tratamiento farmacológico , Hipertensión/genética , Hipertensión/prevención & control , Hipertrofia , Imidazoles/administración & dosificación , Imidazoles/uso terapéutico , Isoquinolinas/administración & dosificación , Isoquinolinas/uso terapéutico , Masculino , Quinapril , Ratas , Ratas Endogámicas SHR , Ratas Endogámicas WKY , Receptor de Angiotensina Tipo 1 , Receptor de Angiotensina Tipo 2 , Receptor de Bradiquinina B2 , Tetrazoles/administración & dosificación , Tetrazoles/uso terapéuticoRESUMEN
We have studied the pharmacokinetics of perindoprilat, the active metabolite of perindopril, in 7 hypertensive patients undergoing haemodialysis after short-term and long-term (1 month) perindopril. We also measured angiotensin-converting enzyme activity. Each subject took 2 mg of perindopril after a 4-hour haemodialysis. Serial blood samples were obtained each hour during dialysis and between dialysis (7 samples over 44 h). Perindoprilat steady state was reached within 5 haemodialysis sessions. There was a high degree of angiotensin converting enzyme inhibition after the first dose. Administration for 1 month did not modify the time to peak perindoprilat concentration but significantly increased the mean maximal concentration: 10.2 versus 26.8 ng.ml-1. The mean accumulation ratio was 3.5. The mean reduction in perindoprilat concentration after dialysis was greater than 50%. Perindoprilat haemodialysis clearance was 62 ml.min-1 after the first administration and 72 ml.min-1 after 1 month. Tolerance of perindopril was good throughout the study. Treatment can be begun with 2 mg of perindopril after haemodialysis in hypertensive patients undergoing haemodialysis.
Asunto(s)
Indoles/farmacocinética , Diálisis Renal , Adulto , Anciano , Inhibidores de la Enzima Convertidora de Angiotensina/farmacología , Presión Sanguínea/efectos de los fármacos , Femenino , Frecuencia Cardíaca/efectos de los fármacos , Humanos , Indoles/efectos adversos , Indoles/farmacología , Masculino , Persona de Mediana Edad , Perindopril , Radioinmunoensayo , UltrafiltraciónRESUMEN
Thirty-six hypertensive patients with impaired renal function entered a long-term study to assess the safety of perindopril. There were 28 men and 8 women of mean age 57.1 +/- 2.0 years (mean +/- SEM). The duration of documented hypertension was 7.3 +/- 1.2 years. Perindopril was given orally in single daily doses. The initial dosage was chosen according to the degree of renal function impairment: 29 patients received 4 mg o.d. [creatinine clearance (Clcr), 42.2 +/- 3.2 ml.min-1] and 7 patients received 2 mg o.d. (Clcr, 22.3 +/- 3.1 ml.min-1). Patients in whom blood pressure was not controlled had their dose doubled and then, if necessary, an additional diuretic therapy was added at subsequent visits. Six patients were withdrawn for adverse events (myocardial infarction, pneumonia, leucopenia in a patient who had lupus, diabetes mellitus, skin rash, epigastric pain), two patients were withdrawn for poor compliance, and three for personal convenience. The mean duration of treatment was 10.2 months with a range of 3-12 months (excluding one patient who died from myocardial infarction in the first days of the study and was not included in the analysis). Systolic and diastolic blood pressure decreased significantly (from 170.5/100.6 +/- 3.4/1.8 mm Hg to 151.8/88.8 +/- 3.0/1.7 mm Hg, n = 35, p less than 0.001). Baseline and final values of plasma creatinine (from 223.7 +/- 22.7 to 234.7 +/- 28.5 mumols/l), Clcr (42.5 +/- 3.2 to 45.7 +/- 4.6 ml.min-1), and kalemia (from 4.4 +/- 0.1 to 4.7 +/- 0.1 mmol/L) were not statistically different.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Presión Sanguínea/efectos de los fármacos , Hipertensión/tratamiento farmacológico , Indoles/uso terapéutico , Fallo Renal Crónico/complicaciones , Administración Oral , Adulto , Anciano , Inhibidores de la Enzima Convertidora de Angiotensina/administración & dosificación , Inhibidores de la Enzima Convertidora de Angiotensina/efectos adversos , Femenino , Frecuencia Cardíaca/efectos de los fármacos , Humanos , Hipertensión/complicaciones , Indoles/administración & dosificación , Indoles/efectos adversos , Pruebas de Función Renal , Masculino , Persona de Mediana Edad , PerindoprilRESUMEN
The case of a 30 month-old boy who presented with isolated severe dilated cardiomyopathy is reported. The diagnosis of systemic carnitine deficiency was confirmed by low serum and tissue carnitine levels. During oral L-carnitine therapy, dramatic improvement of the cardiac function was assessed by radionuclide methods. Myocardial thallium 201 uptake was closely correlated with cardiac function studied by angioscintigraphy. These methods are simple, easily reproducible, non-invasive and involve little radiation. In a case of cardiomyopathy, we suggest an immediate trial of oral carnitine treatment; the efficacy of the therapy can be confirmed by isotopic tests with thallium 201 scintigraphy.
Asunto(s)
Cardiomiopatía Dilatada/diagnóstico por imagen , Carnitina/deficiencia , Radioisótopos de Talio , Cardiomiopatía Dilatada/etiología , Cardiomiopatía Dilatada/fisiopatología , Preescolar , Ecocardiografía , Humanos , Masculino , Pronóstico , CintigrafíaRESUMEN
Hypomelanosis of Ito (incontinentia pigmenti achromians), a sacrococcygeal complex dysembryoma, seizures, severe cerebral lesions, mental retardation, chorioretinal atrophy, hemihypotrophy of the body, and skeletal anomalies are reported in a female infant of North African origin. Karyotype analysis revealed mosaicism for a microdeletion of the proximal region of 15q similar to that observed in Willi-Prader syndrome. The possibility of gene assignment of Ito's disease or that it may represent a nonspecific marker for mosaicism are discussed.
Asunto(s)
Deleción Cromosómica , Cromosomas Humanos Par 15 , Trastornos de la Pigmentación/genética , Bandeo Cromosómico , Femenino , Marcadores Genéticos , Humanos , Lactante , CariotipificaciónRESUMEN
The authors have had the opportunity to see two cases of CNS side effects of Ifosfamide-Mesna association in children. Data in the medical literature about this subject remains poor. Only a few observations are available. In the referred cases, CNS side effects (lethargy, apathy and mutism) appeared a few hours after the second day of treatment and were spontaneously reversible in a few days. After reviewing possible mechanisms of this toxicity the authors pointed out the necessity to keep this type of side effects of Ifosfamide-Mesna association in mind, and to avoid it in susceptible patients.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias Óseas/tratamiento farmacológico , Enfermedades del Sistema Nervioso Central/inducido químicamente , Osteosarcoma/tratamiento farmacológico , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Niño , Femenino , Humanos , Ifosfamida/administración & dosificación , Ifosfamida/efectos adversos , Mesna/administración & dosificación , Mesna/efectos adversosRESUMEN
The serum concentration of parathormone is usually normal in hypophosphatasia, a rare disease with a defect of bone mineralisation and low serum alkaline phosphatase activity. Nevertheless there are three cases in the literature presenting a hyperparathyroidism with or without hypercalcemia. No anomaly of parathyroid was found at autopsy. The authors describe the first cases of hypophosphatasia with low serum concentration of parathormone and raise the possibility of a trouble in the calcium-parathormone feed-back. They also emphasize the interest of the urinary pyrophosphate excretion. Its increase seem to be the most constant and the most specific biological disorder.