Purpose
The active form of vitamin D (1,25(OH)
2
D) contributes to blood flow regulation in skeletal muscle. The aim of the present study was to determine whether this hormone also modulates coronary ...physiology, and thus whether abnormalities in its bioavailability contribute to excess cardiovascular risk in patients with disorders of mineral metabolism.
Methods
As a clinical model of the wide variability in 1,25(OH)
2
D bioavailability, we studied 23 patients (62 ± 8 years) with suspected primary hyperparathyroidism referred for myocardial perfusion imaging because of atypical chest pain and at least one cardiovascular risk factor. Dipyridamole and baseline myocardial blood flow indexes were assessed on G-SPECT imaging of
99m
Tc-tetrofosmin, with normalization of the myocardial count rate to the corresponding first-transit counts in the pulmonary artery. Coronary flow reserve (CFR) was defined as the ratio between dipyridamole and baseline myocardial blood flow indexes. In all patients, parathyroid hormone, 25-hydroxy vitamin D (25(OH)D) and 1,25(OH)
2
D serum levels were determined.
Results
Primary hyperparathyroidism was eventually diagnosed in 15 of the 23 patients. The mean 25(OH)D concentration was relatively low (21 ± 10 ng/mL) while the concentrations of 1,25(OH)
2
D varied widely but within the normal range (mean 95 ± 61 pmol/L). No patient showed reversible perfusion defects on G-SPECT. CFR was not correlated with either the serum concentration of 25(OH)D nor that of parathyroid hormone, but was strictly correlated with the serum level of 1,25(OH)
2
D (
R
= 0.8,
p
< 0.01). Moreover, patients with a 1,25(OH)
2
D concentration below the median value (86 pmol/L) had markedly lower CFR than the other patients (1.48 ± 0.40 vs. 2.51 ± 0.63, respectively;
p
< 0.001).
Conclusion
Bioavailable 1,25(OH)
2
D modulates coronary microvascular function. This effect might contribute to the high cardiovascular risk of conditions characterized by chronic reduction in bioavailability of this hormone.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, SIK, UILJ, UKNU, UL, UM, UPUK, VKSCE, VSZLJ, ZAGLJ
Summary
Purpose: Reproductive dysfunction in epilepsy is attributed to the seizures themselves and also to antiepileptic drugs (AEDs), which affect steroid production, binding, and metabolism. In ...turn, neuroactive steroids may influence neuronal excitability. A previous study in this cohort of consecutive women with epilepsy showed that patients with more frequent seizures had higher cortisol and lower dehydroepiandrosterone sulfate levels than those with rare or absent seizures. The present study was aimed at evaluating, in these same women, the possible relationship between some clinical parameters, seizure frequency, AED therapies, and sex hormone levels.
Methods: Estradiol (E2), progesterone (Pg), sex hormone‐binding globulin (SHBG), and free estrogen index (FEI) were measured during the luteal phase in 113 consecutive females, 16–47 years old, with different epilepsy syndromes on enzyme‐inducing AED (EIAED) and/or non–enzyme‐inducing AED (NEIAED) treatments, and in 30 age‐matched healthy women. Hormonal data were correlated with clinical parameters (age, epilepsy syndrome, disease onset, and duration), seizure frequency assessed on the basis of a seizure frequency score (SFS), and AED therapies.
Results: E2, Pg, and FEI were lower, whereas SHBG levels were higher in the epilepsy patients than in the controls. However, sex steroid and SHBG levels were not different between groups of patients categorized according to SFS. Therapies with EIAEDs accounted for changes in E2 levels and FEI.
Conclusions: Despite globally decreased sex steroid levels in serum, actual hormone titers were not significantly correlated with SFS in consecutive epilepsy women; rather, these hormonal changes were explained by AED treatments, mainly when EIAED polytherapies were given.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Summary
Purpose: Neuroactive sex steroids influence neuron excitability, which is enhanced by estradiol (E2) and decreased by progesterone (Pg). In epilepsy, the production, metabolism, biologic ...availability, and activity of sex hormones may be affected by seizures themselves or by antiepileptic drugs (AEDs). This cross‐sectional observational study was aimed at evaluating the relationships between sex steroids, seizure frequency, and other clinical parameters in women with partial epilepsy (PE) on AED treatments.
Methods: Serum E2, Pg, sex hormone binding globulin (SHBG) levels, free E2 (fE2), and E2/Pg ratios were determined during the follicular and luteal phases in 72 adult women with PE, and in 30 healthy controls. Hormonal data were correlated with seizure frequency, age, body weight, body mass index (BMI), disease onset and duration, and AED therapies.
Results: In patients, E2, fE2, and Pg levels were lower in both ovarian phases, whereas those of SHBG were higher than in controls. No significant changes in hormone levels and in prevalence of anovulatory cycles were observed between patients grouped according to their seizure frequency. However, when compared with those in healthy controls, luteal fE2 and Pg levels were chiefly impaired in women with more frequent seizures, mostly undergoing AED polytherapies, but not in those with absent or rarer seizures.
Conclusions: The actual changes in sex steroid levels and E2/Pg ratios did not explain an increased seizure frequency in adult women with AED‐treated PE, but patients with more severe disease showed more relevant changes in their sex hormone profile and impaired Pg levels during the luteal phase.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Chronic kidney disease (CKD), cardiac damage (CD) and the combination of the two are associated with increased morbidity and death in patients admitted to vascular surgery units. We assessed the ...prevalence of cardiac and renal damage and cardiorenal syndrome (CRS) in 563 patients with abdominal aortic aneurysms (AAA) who underwent cardiac screening before either an endovascular procedure (EVAR) or open surgery (OS) for aneurysm repair. CD was defined by ≥stage B as per the ACC/AHA classification of congestive heart failure (CHF), while CKD was defined by estimated GFR <60 mL/min/1.73 m
2
(CKD-EPI). Anemia World Health Organization (WHO) guidelines and iron deficiency (ID) (criteria for CHF patients) were also calculated. AAA patients were stratified into the following groups: CD, CKD, CRS or none of these conditions no risk factors (NoRF). The prevalence of isolated cardiac and renal structural damage, of combined cardiorenal damage and of ID was 24.1, 15.0, 20.6 and 23.4 %, respectively. The frequency of anemia (mostly unrecognized) among the groups increased from NoRF (12.8 %)/CKD (19 %)/CD (25 %) up to CRS (38.8 %). This large-scale observational study provides clues for the increased CD/CKD risk profiles of unselected AAA patients, and underlines the need for better identification of ID/anemia and for appropriate treatment of CKD and CD before these patients undergo EVAR/OS.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Abstract only
e19038
Background: MCC is a rare cutaneous neuroendocrine neoplasm characterized by an aggressive behavior and a high recurrence rate, generally associated with poor prognosis. Nodal ...and distant metastases are frequent. Aim of this study was to report histological, clinical and prognostic features of a series of 12 patients with nodal MCC in the lack of evidence of a primary. Methods: The cases were collected from a multicentric database: mean age at diagnosis was 67 years; F:M ratio was 1:1.4; mean follow up was 54 months (8-108). Involved nodal sites were: inguinal (9) and axillar (3). All cases had typical MCC immunoprofile: neuroendocrine (CgA, NSE, Syn) and epithelial (CK 20 dot-like) marker positivity. Complete and extensive clinical, dermatologic, radiologic and endoscopic work-up was performed. All patients underwent surgical excision; in one case chemotherapy, in another case biotherapy and in one further case radiotherapy was administered. Results: All cases were in stage III of disease, according to AJCC. All patients were alive without recurrence at the time of the study. The overall mean survival was 52 months. The 4-yr survival was 100%. Conclusions: In patients with nodal metastases of MCC in the absence of a primary lesion, survival seems to be more similar to stage I rather than stage III, since 4-yr survival is reported about 60% for stage III disease in MCC. This finding must still be completely explained. Regression of a small skin primary with nodal metastases or alternatively a primary nodal MCC might be hypothesized. In conclusion, the unknown primary nodal metastatic skin MCC seems to be associated with a more favorable prognosis.
Objective The uremic toxin Indoxyl-3-sulphate (IS), a ligand of Aryl hydrocarbon Receptor (AhR), raises in blood during early renal dysfunction as a consequence of tubular damage, which may be ...present even when eGFR is normal or only moderately reduced, and promotes cardiovascular damage and monocyte-macrophage activation. We previously found that patients with abdominal aortic aneurysms (AAAs) have higher CD14+CD16+ monocyte frequency and prevalence of moderate chronic kidney disease (CKD) than age-matched control subjects. Here we aimed to evaluate the IS levels in plasma from AAA patients and to investigate in vitro the effects of IS concentrations corresponding to mild-to-moderate CKD on monocyte polarization and macrophage differentiation. Methods Free IS plasma levels, monocyte subsets and laboratory parameters were evaluated on blood from AAA patients and eGFR-matched controls. THP-1 monocytes, treated with IS 1, 10, 20 MM were evaluated for CD163 expression, AhR signaling and then induced to differentiate into macrophages by PMA. Their phenotype was evaluated both at the stage of semi-differentiated and fully differentiated macrophages. AAA and control sera were similarly used to treat THP-1 monocytes and the resulting macrophage phenotype was analyzed. Results IS plasma concentration correlated positively with CD14+CD16+ monocytes and was increased in AAA patients. In THP-1 cells, IS promoted CD163 expression and transition to macrophages with hallmarks of classical (IL-6, CCL2, COX2) and alternative phenotype (IL-10, PPARgamma, TGF-Beta, TIMP-1), via AhR/Nrf2 activation. Analogously, AAA sera induced differentiation of macrophages with enhanced IL-6, MCP1, TGF-Beta, PPARgamma and TIMP-1 expression. Conclusion IS skews monocyte differentiation toward low-inflammatory, profibrotic macrophages and may contribute to sustain chronic inflammation and maladaptive vascular remodeling.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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