[Muscle assessment methods for the diagnosis of sarcopenia in cirrhotic patients]. / Métodos de evaluación muscular para el diagnóstico de sarcopenia en pacientes cirróticos.

Sarcopenia is the loss of muscle mass and function. Its presence darkens the prognosis of cirrhotic patients. The gold standard for the description of sarcopenia is the Skeletal Muscle Index (SMI). Thirty-four cirrhotic patients were included. Measurement was carried out through CT of both psoas separately that were then added obtaining the so called "sum of area of 2 psoas", in addition total muscular area, SMI and total area of psoas were measured. Ultrasonography was also performed and the transverse area of the quadriceps rectus anterior was measured by ultrasound and Hand Grip (HG). The correlation between the different measurements was analyzed comparing with the total muscle area, with quadriceps area (r = 0.39; p = 0.019), with total psoas area (r = 0.71; p <0.01), with sum of area of 2 psoas (r = 0.72; p <0.001) and with HG (r = 0.45; p = 0.0069). Compared with SMI, in women HG had 86% sensitivity and 66% specificity (AUC = 0.89). In men, the sum of 2 psoas had 91.7% sensitivity and specificity (AUC = 0.82) and the total area of psoas had 83.3% sensitivity and 76.9% specificity (AUC = 0.8). There was a very good correlation between the tomography methods with the gold standard. The correlation with ultrasound and strength was good. In the evaluation of sensitivity, specificity and AUC, it was not found a useful method when comparing with the SMI.

La sarcopenia es la pérdida de masa y función muscular. Su presencia ensombrece el pronóstico de los pacientes cirróticos. El gold standard para la descripción de sarcopenia es el Skeletal Muscle Index (SMI). Se incluyeron 34 pacientes cirróticos. Se realizó medición a través de tomografía computarizada de ambos psoas por separado, que luego fueron sumados obteniendo lo que se denominó "suma de área de 2 psoas", además se midió área muscular total, SMI y área total de psoas. También se realizó ecografía y se midió el área transversal de recto anterior del cuádriceps por ecografía y Hand Grip (HG). Se analizó la correlación entre las distintas mediciones comparando con el área muscular total, con área de cuádriceps (r = 0.39; P = 0.019), con área total de psoas (r = 0.71; P < 0.01), con suma de área de 2 psoas (r= 0.72; P < 0.001) y con HG (r = 0.45; P = 0.0069). Comparado con el SMI, en mujeres el HG tuvo 86% sensibilidad y 66% especificidad (AUC = 0.89). En hombres la suma de 2 psoas tuvo 91.7% de sensibilidad y especificidad (AUC = 0.82) y el área total de psoas tuvo 83.3% de sensibilidad y 76.9% de especificidad (AUC = 0.8). Hubo muy buena correlación entre los métodos de tomografía con el gold standard, y la correlación con la ecografía y la fuerza fue buena. Evaluando sensibilidad, especificidad y AUC, no se consideró un método útil para ambos sexos, comparado con el SMI.

Métodos de evaluación muscular para el diagnóstico de sarcopenia en pacientes cirróticos / Muscle assessment methods for the diagnosis of sarcopenia in cirrhotic patients

Resumen La sarcopenia es la pérdida de masa y función muscular. Su presencia ensombrece el pronóstico de los pacientes cirróticos. El gold standard para la descripción de sarcopenia es el Skeletal Muscle Index (SMI). Se incluyeron 34 pacientes cirróticos. Se realizó medición a través de tomografía computarizada de ambos psoas por separado, que luego fueron sumados obteniendo lo que se denominó "suma de área de 2 psoas", además se midió área muscular total, SMI y área total de psoas. También se realizó ecografía y se midió el área transversal de recto anterior del cuádriceps por ecografía y Hand Grip (HG). Se analizó la corre lación entre las distintas mediciones comparando con el área muscular total, con área de cuádriceps (r = 0.39; P = 0.019), con área total de psoas (r = 0.71; P < 0.01), con suma de área de 2 psoas (r= 0.72; P < 0.001) y con HG (r = 0.45; P = 0.0069). Comparado con el SMI, en mujeres el HG tuvo 86% sensibilidad y 66% especificidad (AUC = 0.89). En hombres la suma de 2 psoas tuvo 91.7% de sensibilidad y especificidad (AUC = 0.82) y el área total de psoas tuvo 83.3% de sensibilidad y 76.9% de especificidad (AUC = 0.8). Hubo muy buena correlación entre los métodos de tomografía con el gold standard, y la correlación con la ecografía y la fuerza fue buena. Evaluando sensibilidad, especificidad y AUC, no se consideró un método útil para ambos sexos, comparado con el SMI

Abstract Sarcopenia is the loss of muscle mass and function. Its presence darkens the prognosis of cirrhotic patients. The gold standard for the description of sarcopenia is the Skeletal Muscle Index (SMI). Thirty-four cirrhotic patients were included. Measurement was carried out through CT of both psoas separately that were then added obtain ing the so called "sum of area of 2 psoas", in addition total muscular area, SMI and total area of psoas were measured. Ultrasonography was also performed and the transverse area of the quadriceps rectus anterior was measured by ultrasound and Hand Grip (HG). The correlation between the different measurements was analyzed comparing with the total muscle area, with quadriceps area (r = 0.39; p = 0.019), with total psoas area (r = 0.71; p <0.01), with sum of area of 2 psoas (r = 0.72; p <0.001) and with HG (r = 0.45; p = 0.0069). Compared with SMI, in women HG had 86% sensitivity and 66% specificity (AUC = 0.89). In men, the sum of 2 psoas had 91.7% sensitivity and specificity (AUC = 0.82) and the total area of psoas had 83.3% sensitivity and 76.9% specificity (AUC = 0.8). There was a very good correlation between the tomography methods with the gold standard. The correlation with ultrasound and strength was good. In the evaluation of sensitivity, specificity and AUC, it was not found a useful method when comparing with the SMI.

[Hughes-Stovin Syndrome, a case report]. / Síndrome de Hughes-Stovin.

The Hughes-Stovin syndrome is a rare entity characterized by deep vein thrombosis and pulmonary artery aneurysms of unknown etiology and pathogenesis. Some authors considered a variant of Behcet's disease. Its natural course is usually fatal. The symptoms are cough, dyspnea, hemoptysis, chest pain and fever. The treatment goes from steroids and cytotoxic agents to surgery. We present the case of a 41 year old man who shows dyspnea, hemoptysis, and chest pain leading to the diagnosis of deep venous thrombosis of the right leg, lung thromboembolism and pulmonary artery aneurysms. He was treated with high-dose corticosteroids and 6 cyclophosphamide pulses of 1 gram each per 6 months with complete regression of aneurysms and symptomatology.

Síndrome de Hughes-Stovin

El síndrome de Hughes-Stovin es una entidad infrecuente caracterizada por trombosis venosa profunda y aneurismas de la arteria pulmonar, siendo su etiología y patogenia desconocida. Algunos autores la consideran una variante de la enfermedad de Behcet. Su curso natural es generalmente fatal. Se presenta con tos, disnea, hemoptisis, dolor torácico y fiebre. El tratamiento es con esteroides y agentes citotóxicos hasta la cirugía. Presentamos el caso de un hombre de 41 años que consultó por disnea, hemoptisis y dolor torácico, llegándose al diagnóstico de trombosis venosa profunda de miembro inferior derecho, trombo-embolismo de pulmón y aneurismas de arterias pulmonares. Recibió tratamiento con corticoides en altas dosis y 6 pulsos de ciclofosfamida de 1 gramo durante 6 meses, con regresión completa de los aneurismas y de la sintomatología.(AU)

The Hughes-Stovin syndrome is a rare entity characterized by deep vein thrombosis and pulmonary artery aneurysms of unknown etiology and pathogenesis. Some authors considered a variant of Behcets disease. Its natural course is usually fatal. The symptoms are cough, dyspnea, hemoptysis, chest pain and fever. The treatment goes from steroids and cytotoxic agents to surgery. We present the case of a 41 year old man who shows dyspnea, hemoptysis, and chest pain leading to the diagnosis of deep venous thrombosis of the right leg, lung thromboembolism and pulmonary artery aneurysms. He was treated with high-dose corticosteroids and 6 cyclophosphamide pulses of 1 gram each per 6 months with complete regression of aneurysms and symptomatology.(AU)

Síndrome de Hughes-Stovin / Hughes-Stovin Syndrome, a case report

El síndrome de Hughes-Stovin es una entidad infrecuente caracterizada por trombosis venosa profunda y aneurismas de la arteria pulmonar, siendo su etiología y patogenia desconocida. Algunos autores la consideran una variante de la enfermedad de Behcet. Su curso natural es generalmente fatal. Se presenta con tos, disnea, hemoptisis, dolor torácico y fiebre. El tratamiento es con esteroides y agentes citotóxicos hasta la cirugía. Presentamos el caso de un hombre de 41 años que consultó por disnea, hemoptisis y dolor torácico, llegándose al diagnóstico de trombosis venosa profunda de miembro inferior derecho, trombo-embolismo de pulmón y aneurismas de arterias pulmonares. Recibió tratamiento con corticoides en altas dosis y 6 pulsos de ciclofosfamida de 1 gramo durante 6 meses, con regresión completa de los aneurismas y de la sintomatología.

The Hughes-Stovin syndrome is a rare entity characterized by deep vein thrombosis and pulmonary artery aneurysms of unknown etiology and pathogenesis. Some authors considered a variant of Behcet's disease. Its natural course is usually fatal. The symptoms are cough, dyspnea, hemoptysis, chest pain and fever. The treatment goes from steroids and cytotoxic agents to surgery. We present the case of a 41 year old man who shows dyspnea, hemoptysis, and chest pain leading to the diagnosis of deep venous thrombosis of the right leg, lung thromboembolism and pulmonary artery aneurysms. He was treated with high-dose corticosteroids and 6 cyclophosphamide pulses of 1 gram each per 6 months with complete regression of aneurysms and symptomatology.

Enzyme inhibition and induction in liver disease.

This article reviews the influence of liver functional status on pharmacokinetic interactions due to inhibition and induction of drug-metabolizing enzymes. Recent human studies have shown that the magnitude of inhibitory interactions caused by the reversible CYP1A2 inhibitor fluvoxamine decreases as liver function worsens, and virtually vanishes in patients with more advanced hepatocellular insufficiency. This effect of liver dysfunction is independent of the pharmacokinetic characteristics of the CYP1A2 substrate, since it has been observed with both high- and low-clearance drugs. It is most probably due to reduced uptake of the inhibitory drug by the cirrhotic liver. In order to ascertain whether this is a general phenomenon, the following questions remain to be addressed: 1) whether the inhibition of any CYP isoform is reduced in liver disease; 2) whether the effect of liver dysfunction depends on the chemical nature of the inhibitory drug, since both reduced in vivo inhibition and in vitro uptake by the cirrhotic liver have so far been shown only for basic drugs; 3) lastly, if similar effects can also be observed with irreversible and quasi-irreversible inhibitors, as their accumulation kinetics in the hepatocyte may differ from those of a reversible inhibitor. Although many in vivo and in vitro studies have examined the inducibility of drug-metabolizing enzymes in liver disease, available data are incomplete and conflicting, since both well-preserved and severely curtailed responses to inducing agents have been reported. The reasons for these variable responses are most probably methodological, i.e., differences in the type and degree of liver dysfunction of the animals and patients examined, and in the type and dosage of the inducing agent used. Nonetheless, the results of those few studies which used pathologically homogeneous animal or patient groups suggest that, like basal enzyme expression, drug-inducible expression is also substantially preserved in mild to moderate liver disease, whereas it is lost in severe hepatic dysfunction. For a definitive conclusion, further studies are necessary which examine etiologically homogeneous patient groups and stratify patients rigorously according to their functional hepatic reserve. Such studies should also examine inducers with different physicochemical properties and acting by different mechanisms, since the expression of both hepatic transporters and nuclear receptors may be differentially affected by liver function impairment.

Differential effect of chronic renal failure on the pharmacokinetics of lidocaine in patients receiving and not receiving hemodialysis.

BACKGROUND AND OBJECTIVES: The effect of chronic renal failure (CRF) on the pharmacokinetics of lidocaine, a drug cleared almost exclusively by hepatic metabolism, has thus far only been evaluated in patients undergoing regular hemodialysis. This study had 2 objectives: (1) to investigate the effect of CRF on the pharmacokinetics of lidocaine in both patients undergoing hemodialysis and patients not undergoing hemodialysis and (2) to test the effects of plasma from the patients examined and of lidocaine metabolites possibly accumulated in vivo on lidocaine biotransformation in vitro. METHODS: In a clinical investigation we studied the kinetics of lidocaine and its metabolites, monoethylglycinexylidide (MEGX) and glycinexylidide (GX), after intravenous injection of 1 mg/kg lidocaine in 15 healthy volunteers (creatinine clearance [CL(cr)] >80 mL/min x 1.73 m(-2)), 10 subjects with moderate renal insufficiency (CL(cr) between 30 and 60 mL/min x 1.73 m(-2)), 10 subjects with severe renal insufficiency (CL(cr) <30 mL/min x 1.73 m(-2)), and 10 functionally anephric patients undergoing long-term hemodialysis. In experiments in vitro we determined the effects of plasma and GX on the formation rate of the primary lidocaine metabolite, MEGX, by use of human liver microsomes. RESULTS: In patients not undergoing hemodialysis, lidocaine kinetic parameters were altered in proportion to the degree of renal function impairment, but only in patients with severe renal insufficiency were differences statistically significant: clearance was about half that of control subjects (mean +/- SD, 6.01 +/- 2.54 mL/min x kg versus 11.87 +/- 2.97 mL/min x kg; P < .001), and half-life was approximately doubled (4.55 +/- 1.71 hours versus 2.24 +/- 0.55 hours, P < .001). No such alterations were observed in patients undergoing regular hemodialysis, whose values were similar to those of the control group. The steady-state volume of distribution and MEGX levels were independent of renal function, whereas GX levels were more than double those of control subjects (P < .05) in all CRF groups. No inhibitory effect of plasma was observed, for any of the subjects examined, on lidocaine biotransformation in vitro. GX was found to be a competitive inhibitor, but its apparent inhibition constant value (52 +/- 6 micromol/L) was 2 orders of magnitude higher than its concentrations in vivo. CONCLUSIONS: Our in vivo findings have both clinical and methodologic implications: (1) Lidocaine dose adjustment may be required in patients with severe renal insufficiency who are not receiving hemodialysis. (2) Results of studies evaluating the effect of CRF on metabolic drug disposition are not of general validity, unless both patients undergoing hemodialysis and patients not undergoing hemodialysis have been examined. Our in vitro observations exclude that impairment of lidocaine disposition is the result of direct inhibition of metabolizing enzymes by accumulated metabolites or uremic toxins. Alternative mechanisms, suggested by the results of recent in vitro studies, are discussed.