Familial SDHB gene mutation in disseminated non-hypoxia-related malignant paraganglioma treated with [90Y]Y/[177Lu]Lu- DOTATATE.

Familial paraganglioma may be related to mutations in succinate dehydrogenase (SDH) enzyme complex genes. Among patients with hereditary paraganglioma, SDH subunit B (SDHB) gene mutations are associated with the highest morbidity and mortality related to a higher malignancy rate. We report a family with the c.689G>A (p.Arg230His) mutation in the SDHB gene identified in two family members, a father and his daughter. While the 14-year-old daughter had no evidence of clinical disease, recurrent and later disseminated [131I]metaiodobenzylguanidine uptake-negative head and neck paraganglioma with multiple bone metastases developed in the father who underwent peptide receptor radionuclide therapy with [90Y]Y/[177Lu]Lu-dodecane tetraacetic acid octreotate (DOTATATE) at the time of the genetic diagnosis. This treatment was repeated 6 years later due to disease progression and the patient, who is currently 49 years old, remains alive and in good overall clinical condition at 8 years of follow-up after the original presentation at our unit. The growing armamentarium of imaging methods available for such patients may inform decision making regarding choice of the optimal treatment approach, potentially contributing to improved outcomes.

Functional polymorphism of the renalase gene is associated with cardiac hypertrophy in female patients with aortic stenosis.

Renalase decreases circulating catecholamines concentration and is important in maintaining primary cellular metabolism. Renalase acts through the plasma membrane calcium ATPase 4b in the heart, which affects pressure overload but not exercise induced heart hypertrophy. The aim of this study was to test the association between a functional polymorphism Glu37Asp (rs2296545) of the renalase gene and left ventricular hypertrophy in a large cohort of patients with aortic stenosis. The study group consisted of 657 patients with aortic stenosis referred for aortic valve replacement. Preoperative echocardiographic assessment was performed to obtain cardiac phenotypes. Generalized-linear models were implemented to analyze data using crude or full model adjusted for selected clinical factors. In females, the Asp37 variant of the Glu37Asp polymorphism was associated with higher left ventricular mass (p = 0.0021 and p = 0.055 crude and full model respectively), intraventricular septal thickness (p = 0.0003 and p = 0.0143) and posterior wall thickness (p = 0.0005 and p = 0.0219) all indexed to body surface area, as well as relative wall thickness (p = 0.001 and p = 0.0097). No significant associations were found among the male patients. In conclusion, we have found the association of the renalase Glu37Asp polymorphism with left ventricle hypertrophy in large group of females with aortic stenosis. The Glu37Asp polymorphism causes not only amino-acid substitution in FAD binding domain but may also change binding affinity of the hypoxia- and hypertrophy-related transcription factors and influence renalase gene expression. Our data suggest that renalase might play a role in hypertrophic response to pressure overload, but the exact mechanism requires further investigation.

Association of the common genetic polymorphisms and haplotypes of the chymase gene with left ventricular mass in male patients with symptomatic aortic stenosis.

We investigated the association between polymorphisms and haplotypes of the chymase 1 gene (CMA1) and the left ventricular mass index (LVM/BSA) in a large cohort of patients with aortic stenosis (AS). Additionally, the gender differences in cardiac remodeling and hypertrophy were analyzed. The genetic background may affect the myocardial response to pressure overload. In human cardiac tissue, CMA1 is involved in angiotensin II production and TGF-ß activation, which are two major players in the pathogenesis of hypertrophy and fibrosis. Preoperative echocardiographic data from 648 patients with significant symptomatic AS were used. The LVM/BSA was significantly lower (p<0.0001), but relative wall thickness (RWT) was significantly higher (p = 0.0009) in the women compared with the men. The haplotypes were reconstructed using six genotyped polymorphisms: rs5248, rs4519248, rs1956932, rs17184822, rs1956923, and rs1800875. The haplotype h1.ACAGGA was associated with higher LVM/BSA (p = 9.84 × 10(-5)), and the haplotype h2.ATAGAG was associated with lower LVM/BSA (p = 0.0061) in men, and no significant differences were found in women. Two polymorphisms within the promoter region of the CMA1 gene, namely rs1800875 (p = 0.0067) and rs1956923 (p = 0.0015), influenced the value of the LVM/BSA in males. The polymorphisms and haplotypes of the CMA1 locus are associated with cardiac hypertrophy in male patients with symptomatic AS. Appropriate methods for the indexation of heart dimensions revealed substantial sex-related differences in the myocardial response to pressure overload.

Expression of eotaxins in the material from nasal brushing in asthma, allergic rhinitis and COPD patients.

BACKGROUND: Asthma and COPD are non-infectious inflammatory diseases of the respiratory tract. Allergic rhinitis can be assumed as an intermediate condition between healthy and asthmatic state. Eotaxins are important indicators of allergic reaction. They are strong chemoattractants mainly for eosinophils but also for other cells. OBJECTIVE: We measured the level of eotaxin expression and inflammatory cell count in the material from nasal brushing in healthy controls and in patients with allergic rhinitis, asthma, and COPD. We studied the correlation between the eotaxin gene expression level in the material from nasal brushing and respiratory tests in asthma and COPD patients. METHODS: Expression of eotaxins was measured using quantitative RT-PCR. Number of eotaxin transcript copies was evaluated using real time PCR standard curve method. RESULTS: Of all eotaxins CCL24 had the highest expression in the material from nasal brushing, and its level was increased in allergic asthma. CCL11 was significantly increased in the material from nasal brushing of COPD patients. Increased levels of all three eotaxins were observed in the material from nasal brushing of patients with allergic rhinitis in season. The levels of CCL26 expression and FEV1/FVC factor were correlated negatively in the asthma group and positively in the COPD group. CONCLUSIONS: Eotaxins are crucial factors of allergic, asthmatic and also COPD inflammatory reactions. Our results suggest a dual role of CCL26 - it can act as a negative regulator for neutrophils in COPD, while in asthma it may act as a chemoatractant of eosinophils and other cells into the lung.

Can angiotensin II +1675 G/A type 2 receptor gene polymorphism be a marker of left ventricular hypertrophy in patients with aortic stenosis?

BACKGROUND AND AIM OF THE STUDY: Activation of the angiotensin II type 2 receptor (AT2R) gene lowers blood pressure, inhibits endothelial and smooth muscle proliferation, and modifies left ventricular hypertrophy (LVH) and fibrosis. Recently, several studies on the presence and importance of AT2R polymorphism for cardiovascular pathology have been reported. The study aim was to investigate any relationship between +1675 G/A AT2R polymorphism and the degree of LVH in patients with aortic stenosis (AS). METHODS: The influence of +1675 G/A AT2R gene polymorphism on AS severity, degree of LVH and systolic function was analyzed in 308 patients (185 men, 123 women; mean age 61.5 +/- 10 years) with significant AS. RESULTS: Due to chromosome X localization of the AT2R gene, the analysis was performed separately in males and females. The prevalence of genotypes was 32.8% for AA, 40.8% for AG, and 26.4% for GG in females; and 52.9% and 47.1% for the A and G alleles, respectively, in males. No correlation was found between +1675 G/A AT2R polymorphism and LVH. The only significant difference was a lower left ventricular ejection fraction (LVEF) and a greater end-systolic LV dimension in males carrying the A allele as compared to allele G carriers. The A allele was more frequently observed in patients with LVEF < 40%. In the multivariate analysis, presence of the A allele was significantly related to LVEF (adjusted for age, hypertension, coronary artery disease), although the impact was of borderline statistical significance (p = 0.04) and explained only 2% of LVEF variance. CONCLUSION: The study results indicate that the +1675 G/A AT2R gene polymorphism cannot be considered as a marker of LVH in patients with AS, but its negative influence on LVEF in A allele carriers may be considered as a marker of premature left ventricular decompensation in males.

[Heart failure following lumbar surgery]. / Niewydolnosc serca u chorej po operacyjnym leczeniu dyskopatii w odcinku ledzwiowym kregoslupa.

High-output heart failure may be caused by an arteriovenous fistula. A case is reported of an arteriovenous fistula following discectomy.