Involvement of the -420C>G RETN polymorphism in myocardial fibrosis in patients with hypertrophic cardiomyopathy.

AIMS: Hypertrophic cardiomyopathy (HCM) is characterized by left ventricular hypertrophy and fibrosis. HCM is an autosomal-dominant disease caused by more than 400 mutations in sarcomeric genes. Changes in nonsarcomeric genes contribute to its phenotypic heterogeneity. Cardiac fibrosis can be studied using late gadolinium enhancement (LGE) cardiac magnetic resonance imaging. We evaluated the potential role of two polymorphisms in nonsarcomeric genes on interstitial fibrosis in HCM. MATERIALS AND METHODS: Two polymorphisms in nonsarcomeric genes [ACE (deletion of 287 bp in the 16th intron) and RETN (-420C>G)] were analysed in 146 HCM patients. Cardiac fibrosis was assessed using LGE to determine the number of affected segments. RESULTS: Allelic frequencies in ACE and RETN polymorphisms were consistent with the Hardy-Weinberg equilibrium (both P > 0.05). We found that the presence of the polymorphic allele in the -420C>G RETN polymorphism was independently associated with the number of affected segments of LGE (P = 0.038). Increased circulating resistin concentration, measured by enzyme-linked immunosorbent assay, was associated with a higher degree of cardiac fibrosis. Myocardial fibrosis, assessed by Masson's trichrome staining, was associated with the -420C>G RETN polymorphism in 46 tissue samples obtained by septal myectomy (P = 0.044). CONCLUSIONS: The -420C>G RETN polymorphism was independently associated with the degree of cardiac fibrosis, assessed by LGE, in patients with HCM. In addition, there was an association between the polymorphism and the circulating resistin levels as well as with myocardial fibrosis in tissues obtained by myectomy. Investigating the physiological implication of the RETN polymorphism in HCM in combination with the use of imaging technologies might help to establish the severity of disease in patients with HCM.

Prognostic value of two polymorphisms in non-sarcomeric genes for the development of atrial fibrillation in patients with hypertrophic cardiomyopathy.

BACKGROUND: Several non-sarcomeric genes have been postulated to act as modifiers in the phenotypic manifestations of hypertrophic cardiomyopathy (HCM). The development of atrial fibrillation (AF) in HCM has adverse prognostic implications with increased thromboembolism and functional class impairment. AIM: We tested the hypothesis that 2 non-sarcomeric genes [CYP11B2 (-344T>C) and COL1A1 (2046G>T)] are associated with the development of AF. DESIGN: Prospective study. METHODS: Two polymorphisms in non-sarcomeric genes [CYP11B2 (-344T>C) and COL1A1 (2046G>T)] were analysed in 159 HCM patients (49.3 ± 14.9 years, 70.6% male) and 136 controls. All subjects were clinically stable and in sinus rhythm at entry in the study, without ischemic heart disease or other significant co-morbidities that could mask the effect of the analysed polymorphisms (i.e. previous AF). Thirty-nine patients (24.4%) developed AF during a median follow-up of 49.5 months. RESULTS: Patients with the -344T>C polymorphism in CYP11B2 gene had a higher risk for AF development [HR: 3.31 (95% CI 1.29-8.50); P = 0.008]. In a multivariate analysis, the presence of the C allele in CYP11B2 gene [HR: 3.02 (1.01-8.99); P = 0.047], previous AF [HR: 2.81 (1.09-7.23); P = 0.033] and a left atrial diameter of ≥42 mm [HR: 2.69 (1.01-7.18); P = 0.048] were independent predictors of AF development. The presence of the polymorphic allele was associated with higher aldosterone serum levels. CONCLUSION: We have shown for the first time that the CYP11B2 polymorphism is an independent predictor for AF development in HCM patients. This highlights the importance of non-sarcomeric genes in the phenotypic heterogeneity of HCM. The association with higher aldosterone serum levels could relate to greater fibrosis and cardiac remodelling.

[Surgical stratification of renal carcinoma with extension into inferior vena cava]. / Estratégia quirúirgica en el carcinoma de células renales con extensión a la circulación venosa.

Renal cell carcinoma with inferior vena cava thrombus is relatively uncommon and complicates radical nefrectomy. During the past twenty years our hospital have substantially contributed to the surgical stratification of renal cell carcinoma with extension into inferior vena cava through different techniques. The reason for this article is to discuss the mote efficient and appropiate surgical technique for this pathology. We believe that the diagnosis of vena caval invasion and level of tumoral extension is based on radiological examinations and it is crucial for the success of the surgery. We consider that the use of vena caval filter applied preoperatively could prevent the risk of thromboembolism during and after the surgery. The use of prosthetic grafts is unusual, because the long standing obstruction caused by the tumor thrombus will develope extensive collateral circulation which works as a natural veno-venous bypass. Finally, we try to avoid the use of veno-venous and cardiopulmonar bypass with or without complete hypothermic circulatory arrest due to the high association with adverse outcomes and mortality.

Analysis of a quantitative PCR assay for CMV infection in liver transplant recipients: an intent to find the optimal cut-off value.

BACKGROUND: Preemptive therapy required highly predictive tests for CMV disease. CMV antigenemia assay (pp65 Ag) has been commonly used for rapid diagnosis of CMV infection. Amplification methods for early detection of CMV DNA are under analysis. OBJECTIVES: To compare two diagnostic methods for CMV infection and disease in this population: quantitative PCR (qPCR) performed in two different samples, plasma and leukocytes (PMNs) and using a commercial diagnostic test (COBAS Amplicor Monitor Test) versus pp65 Ag. STUDY DESIGN: Prospective study conducted in liver transplant recipients from February 2000 to February 2001. RESULTS: Analyses were performed on 164 samples collected weekly during early post-transplant period from 33 patients. Agreements higher than 78% were observed between the three assays. Optimal qPCR cut-off values were calculated using ROC curves for two specific antigenemia values. For antigenemia >or=10 positive cells, the optimal cut-off value for qPCR in plasma was 1330 copies/ml, with a sensitivity (S) of 58% and a specificity (E) of 98% and the optimal cut-off value for qPCR-cells was 713 copies/5x10(6) cells (S:91.7% and E:86%). Using a threshold of antigenemia >or=20 positive cells, the optimal cut-off values were 1330 copies/ml for qPCR-plasma (S 87%; E 98%) and 4755 copies/5x10(6) cells for qPCR-cells (S 87.5%; E 98%). Prediction values for the three assays were calculated in patients with CMV disease (9 pts; 27%). Considering the assays in a qualitative way, the most sensitive was CMV PCR in cells (S: 100%, E: 54%, PPV: 40%; NPV: 100%). Using specific cut-off values for disease detection the sensitivity, specificity, PPV and NPV for antigenemia >or=10 positive cells were: 89%; 83%; 67%; 95%, respectively. For qPCR-cells >or=713 copies/5x10(6) cells: 100%; 54%; 33% and 100% and for plasma-qPCR>or=1330 copies/ml: 78%, 77%, 47%, 89% respectively. CONCLUSIONS: Optimal cut-off for viral load performed in plasma and cells can be obtained for the breakpoint antigenemia value recommended for initiating preemptive therapy with high specificities and sensitivities. Diagnostic assays like CMV pp65 Ag and quantitative PCR for CMV have similar efficiency and could be recommended as methods of choice for diagnosis and monitoring of active CMV infection after transplantation.

Estratégia quirúrgica en el carcinoma de células renales con extensión a la circulación venosa / Surgical stratification of renal carcinoma with extension into inferior vena cava

El carcinoma de células renales con trombo en vena cava inferior es una patología relativamente rara, que complica la nefrectomía radical. Durante los pasados veinte años nuestro hospital ha contribuido sustancialmente a la estratificación quirúrgica del carcinoma de células renales con extensión a la vena cava a través de diferentes técnicas. El objetivo de este artículo es describir las diferentes estrategias quirúrgicas necesarias y más apropiadas para el tratamiento de los distintos niveles del trombo tumoral. Consideramos que el diagnóstico de la invasión de la vena cava por el tumor y el nivel de extensión tumoral están basados en exámenes radiológicos, los cuales son determinantes a la hora del planteamiento quirúrgico y éxito de la cirugía. Somos partidarios del uso de filtros de vena cava colocados. Preoperatoriamente para prevenir el riesgo de tromboembolismos pulmonares durante y después de la cirugía. El uso de prótesis de cava es excepcional, debido a que la obstrucción crónica producida por el trombo tumoral, permitirá el desarrollo de una extensa circulación colateral que actuará como un bypass veno-venoso. Por último, intentamos evitar el uso de bypass veno-venoso o bypass cardiopulmonar con o sin hipotermia y parada cardiocirculatoria, debido a la alta morbimortalidad que conllevan (AU)

Renal cell carcinoma with inferior vena cava thrombus is relatively uncommon and complicates radical nefrectomy. During the past twenty years our hospital have substantially contributed to the surgical stratification of renal cell carcinoma with extension into inferior vena cava through different techniques. The reason; for this article is to discuss the more efficient and appropiate surgical technique for this pathology. We believe that the diagnosis of vena caval invasion and level of tumoral extension is based on radiological examinations and it is crucial for the success of the surgery. We consider that the use of vena caval filter applied preoperatively could prevent the risk of thromboembolism during and after the surgery. The use of prosthetic; grafts is unusual, because the long standing obstruction caused by the tumor thrombus will develope extensive collateral circulation which works as a natural veno-venous bypass. Finally, we try to avoid the use of veno-venous and cardiopulmonar bypass with or without complete hypothermic circulatory arrest due to the high association with adverse outcomes and mortality (AU)

Aspergillus antigenemia sandwich-enzyme immunoassay test as a serodiagnostic method for invasive aspergillosis in liver transplant recipients.

BACKGROUND: Invasive aspergillosis (IA) is an important cause of mortality in liver transplant patients. Clinical and microbiological diagnosis is difficult, and it is frequently achieved only after autopsy. Early diagnosis and antifungal therapy could improve the survival of these patients. METHODS: A retrospective case-control study of IA in liver transplant recipients (OLT) was performed to determine the value of the detection of galactomannan Aspergillus antigen in serum using a sandwich-ELISA test (Platelia, Sanofi Diagnostic Pasteur). Stored frozen serum specimens obtained during the posttransplantation period were used. RESULTS: Fourteen cases of IA were diagnosed in 240 OLT recipients (IA incidence: 5.8%) during 5 years with 13 deaths (mortality: 93%). Nine case patients and 33 control patients met the criteria required for being considered "valid" for antigenemia analysis. In five of the nine case patients, a serum sample was positive for Aspergillus antigenemia detection. The median value was 5.7 ng/ml (range: 1.6-6.6). Sensitivity of the test was 55.6%, specificity was 93.9%, the positive predictive value was 71.4%, and the negative predictive value was 88.6%. The likelihood ratio of a positive test was 9.2. CONCLUSIONS: Galactomannan detection in serum could be useful for an early diagnosis of IA in OLT recipients.

Alteraciones visuales inducidas por digoxina con niveles terapéuticos / Induced visual alterations with therapeutic blood levels

Caso clínico: Presentamos el caso clínico de una paciente que acudió al Servicio de Oftalmología por referir fotopsias. Tras una exploración minuciosa no se constató ninguna alteración visual que justificara la sintomatología. Como único antecedente personal de interés encontramos el inicio del tratamiento con digital dos meses antes. Ante la sospecha de una intoxicación digitálica, se remitió a la paciente para su estudio en el Servicio de Urgencias. Discusión: Tras los estudios realizados se decidió retirar el tratamiento con digitálicos, lo que conllevó la mejoría subjetiva de la paciente y la desaparición de las alteraciones visuales. No debemos olvidar que la toxicidad ocular de la digoxina puede aparecer tanto con niveles tóxicos del fármaco en sangre, como con niveles terapéuticos, y es, en este caso, cuando el cuadro puede pasar desapercibido si se confía únicamente en la digoxinemia (AU)

[Visual disorders induced by therapeutic levels of digoxin]. / Alteraciones visuales inducidas por digoxina con niveles terapéuticos.

CASE REPORT: An elderly patient was referred to the ophthalmologist for evaluation of photopsia. An ophthalmic examination demonstrated no objective visual alterations. The patient had been receiving digitalis for two months. We suspected digitalis intoxication and the patient was remitted to the Emergency Service. The patient's digoxin blood level was normal. We obtained a rapid improvement in the patient's symptoms by discontinuing the medication. DISCUSSION: We must remember that ocular toxicity may occur with therapeutic blood level of the medication and not only when the intoxication appears.

Selection of Candida glabrata strains with reduced susceptibility to azoles in four liver transplant patients with invasive candidiasis.

The cases of four liver transplant recipients who developed invasive candidiasis (2 cholangitis, 1 perihepatic abscess, 1 candidemia) due to azole-resistant, Candida glabrata are reported. Three patients were receiving azolic compounds (2 itraconazole, 1 fluconazole) when the infection was diagnosed. All four patients received fluconazole as intestinal decontamination during the first three weeks post transplantation. The infections occurred two months after transplantation in all patients, and in one patient Candida infection was the direct cause of death. Infection of the biliary tree was the origin of candidiasis in three patients; the fourth patient developed neutropenic-related candidemia. Fluconazole MICs exceeded 16 micrograms/ml in all cases; itraconazole MICs were 16, 2, 1, and 2 micrograms/ml, respectively. The potential role of Candida species other than albicans in these patients after administration of azole agents is discussed.