RESUMEN
STUDY OBJECTIVE: Hyperuricemia occurs frequently in patients with myeloproliferative and lymphoproliferative disorders and in patients with congenital heart disease associated with polycythemia. Whether hyperuricemia is common in patients with severe pulmonary hypertension is not known. DESIGN, PATIENTS, MEASUREMENTS: In the Pulmonary Hypertension Center at the University of Colorado Health Sciences Center between September 1991 and August 1997, 442 consecutive patients were evaluated with right heart catheterization; 191 patients also had a measurement of the serum uric acid (UA) in close temporal proximity to the hemodynamic evaluation. RESULTS: Of the 191 patients with a complete data set, 99 patients had primary pulmonary hypertension (PPH) and 92 had secondary pulmonary hypertension. For the entire cohort with severe pulmonary hypertension (n = 191), there was a positive correlation between the natural logarithm of the serum UA (lnUA) and the mean right atrial pressure (RAP; r = 0.47; p < 0.001). When analyzed separately, the correlation between lnUA and RAP was stronger in the patients with PPH (r = 0.642; p < 0.001). This correlation cannot be explained by diuretic use or impaired hepatocellular function. Neither mean pulmonary artery pressure nor cardiac output was as well correlated with the RAP when compared with the lnUA. Some patients with PPH had serum UA measurements repeated during treatment with chronic IV prostacyclin infusion. Eleven of these 18 patients (61%) demonstrated a decrease in serum UA during prostacyclin treatment. CONCLUSION: There is a positive correlation between the RAP elevation and the serum UA levels in patients with PPH. Serum UA levels drop in some, but not all PPH patients during chronic prostacyclin infusion therapy.
Asunto(s)
Hipertensión Pulmonar/sangre , Ácido Úrico/sangre , Adulto , Antihipertensivos/administración & dosificación , Antihipertensivos/uso terapéutico , Biomarcadores/sangre , Cateterismo Cardíaco , Colorimetría , Epoprostenol/administración & dosificación , Epoprostenol/uso terapéutico , Atrios Cardíacos/fisiopatología , Humanos , Hipertensión Pulmonar/tratamiento farmacológico , Hipertensión Pulmonar/fisiopatología , Infusiones Intravenosas , Persona de Mediana Edad , Presión Esfenoidal Pulmonar/efectos de los fármacos , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Angiotensin II causes pulmonary vasoconstriction in man and in animals, and angiotensin-converting enzyme (ACE) inhibitors have prevented the development of chronic pulmonary hypertension in animals models. Angiotensin II may contribute to lung vascular remodeling in pulmonary hypertensive disease, since cilazapril, an inhibitor of ACE, reduces pulmonary vascular medical thickening in chronically hypoxic rats with established pulmonary hypertension. Furthermore, the ACE DD genotype, which has been associated with increased circulating and tissue ACE activity, has been associated with left ventricular hypertrophy in human hypertensive disorders. The ACE DD genotype may also 'permit' a greater hypertrophic adaptation of the pressure-over-loaded right ventricle. In fact, we have shown that pulmonary hypertension patients with maintained cardiac output and less right-heart failure fall into the group with the DD genotype and that patients with a low cardiac output and more severe right-heart failure fall into the group with the non-DD genotype, supporting the hypothesis. We assessed cardiopulmonary hemodynamics in patients with primary (unexplained) pulmonary hypertension and segregated the patients based on their ACE genotype. For similar mean pulmonary artery pressures in the DD and non-DD groups, the cardiac output was substantially lower in the patients with the non-DD genotype, whereas the values for mean right atrial pressure and pulmonary vascular resistance were double when compared with the DD group. Our data show that the ACE DD genotype is prevalent in patients with severe pulmonary hypertension and is a marker of maintained right ventricular function.
Asunto(s)
Hipertensión Pulmonar/fisiopatología , Peptidil-Dipeptidasa A/fisiología , Resistencia Vascular/efectos de los fármacos , Disfunción Ventricular Derecha/fisiopatología , Animales , Cilazapril/uso terapéutico , Modelos Animales de Enfermedad , Electroforesis en Gel de Agar , Genotipo , Hemodinámica/efectos de los fármacos , Humanos , Hipertensión Pulmonar/tratamiento farmacológico , Masculino , Reacción en Cadena de la Polimerasa , Ratas , Ratas Sprague-Dawley , Disfunción Ventricular Derecha/tratamiento farmacológicoAsunto(s)
Anticuerpos Antinucleares/análisis , Hipertensión Pulmonar/inmunología , Hipotiroidismo/inmunología , Adulto , Enfermedades Autoinmunes , Epoprostenol/uso terapéutico , Femenino , Humanos , Hipertensión Pulmonar/complicaciones , Hipertensión Pulmonar/tratamiento farmacológico , Hipotiroidismo/complicaciones , Persona de Mediana Edad , Enfermedad de Raynaud/complicaciones , Tiroiditis/complicacionesRESUMEN
A technique is described for the isolation and characterisation of monocytes from 15 ml of human peripheral blood. After density gradient centrifugation over Ficoll-Hypaque, monocytes are purified further by substrate adherence under carefully defined conditions. The use of a simple microwell slide system permits the production of multiple small-scale monolayer populations which can be characterised further in terms of their histochemical reactivity (combined stain for chloroacetate and non-specific esterases); endocytic capacity (latex particles); Fc (sensitised ox erythrocytes) and C3 (serum-coated yeast) receptor expression; and precursor maturation potential (7-day cultures). Evidence of considerable cellular heterogeneity is presented.
Asunto(s)
Monocitos/fisiología , Separación Celular/métodos , Células Cultivadas , Centrifugación por Gradiente de Densidad , Complemento C3/inmunología , Endocitosis , Humanos , Receptores de Complemento/inmunología , Receptores Fc/inmunologíaRESUMEN
A simple method is described which allows sequential monitoring of the endocytic activity of blood and synovial fluid cells from rheumatoid arthritis patients undergoing therapy with levamisole. Evidence of immediate (24 hours) and long-term (5-7 weeks) cellular phagocytic enhancement is presented.
Asunto(s)
Artritis Reumatoide/inmunología , Levamisol/uso terapéutico , Fagocitosis/efectos de los fármacos , Artritis Reumatoide/tratamiento farmacológico , Femenino , Humanos , Masculino , Monocitos/inmunología , Neutrófilos/inmunología , Proyectos Piloto , Líquido Sinovial/inmunología , Factores de TiempoRESUMEN
Proliferation of macrophages in chronic inflammatory loci is an essential part of granuloma development and as such helps to defend the host against dissemination of harmful microorganisms. Its induction seems to depend in part on local appearance of soluble mitogenic factors since sterile cell-free exudates will induce mitotic activity in vitro in a macrophage population otherwise unable to divide. Macrophage proliferation is probably checked and controlled by inherent restrictions on the number of divisions possible. This in turn probably depends on the rapid appearance of gross chromosomal defects, the effete cells being eliminated by their incorporation into multinucleate giant cells which then form non-viable polyploid cells.