Distribution of plasma cardiac troponin I values in healthy subjects: pathophysiological considerations

BACKGROUND: The aim of this study was to evaluate the distribution of cardiac troponin I (cTnI) values, measured by the ADVIA TnI-Ultra method (Siemens Medical Solutions Diagnostics SrL) in healthy subjects and to characterize its relation to gender, age, as well as to N-terminal fragment of pro-brain natriuretic peptide (NT-proBNP). METHODS: A Caucasian population of 692 healthy subjects (311 males and 381 females) with a mean (SD) age of 45.3 (17.3) years [range 11-89 years; females 46.5 (17.3) years, males 43.8 (17.1) years] was enrolled. The presence of cardiac or systemic acute or chronic diseases was excluded by history and accurate clinical evaluation. RESULTS: A significant difference was found between the cTnI values in men and women (men: median 0.012 microg/L, range from undetectable values to 0.196 microg/L; women: median 0.008 microg/L, range from undetectable values to 0.130 microg/L; p<0.0001 by Mann-Whitney U-test). When a multiple regression analysis was performed, NT-proBNP, gender and age significantly contributed to the regression with cTnI (R=0.444, p<0.0001). CONCLUSIONS: Our data indicate that cut-off values, based on the 99th percentile of cTnI distribution in apparently healthy subjects, can significantly vary according to age and gender of the reference population.     

Modification of the content of plasma protein carbonyl groups in donors after granulocyte colony stimulating factor-induced stem cell mobilization.

Granulocyte-colony stimulating factor (G-CSF), the most established agent for the mobilization of stem cells in current clinical practice, could induce a condition of oxidative stress. Herein plasmatic levels of protein carbonyl groups (a biomarker of oxidative stress) were measured in a group of donors given recombinant human G-CSF (rHuG-CSF) at different times: (1) before starting rHuG-CSF administration, (2) on day 5 of rHuG-CSF administration, (3) on the same day immediately after the end of the first leukapheresis procedure and (4) one week after rHuG-CSF withdrawal. Plasma levels of protein carbonyl groups enhanced significantly in donors after 5 days of rHuG-CSF treatment and appeared further slightly increased following leukapheresis procedure; 7 days following rHuG-CSF withdrawal, they showed a tendency to normalization. These findings may contribute to better understand the oxidative reactions following rHuG-CSF treatment and leukapheresis.     

Long-Term Follow-Up of a Donor versus No-Donor Comparison in Patients with Multiple Myeloma in First Relapse after Failing Autologous Transplantation

We report the long-term clinical outcomes of a retrospective multicenter study that enrolled 169 patients with multiple myeloma (MM) in first relapse after failing autologous stem cell transplantation (SCT). After HLA typing at relapse, 79 patients with a suitable donor, 72 (91%) of whom eventually underwent salvage allogeneic SCT (allo-SCT), were compared with 90 patients without a donor who were treated with multiple lines of salvage treatment with bortezomib and/or immunomodulatory agents. At a median follow-up of 30 months (range, 2-180 months) for all patients and 110 months (range, 38-180 months) for surviving patients, 7-year progression-free survival (PFS) was 18% in the donor group and 0% in the no-donor group (hazard ratio [HR], 2.495; 95% confidence interval [CI], 1.770-3.517; P?<?.0001). Seven-year overall survival (OS) was 31% in the donor group and 9% in the no-donor group (HR, 1.835; 95% CI, 1.306-2.577; P?<?.0001). By multivariate analysis, chemosensitivity to salvage treatments and presence of a suitable donor were significantly associated with better PFS and OS. The long-term follow-up of this study confirms the significant PFS benefit and provides new evidence of an OS advantage for patients with MM who have a suitable donor and undergo allo-SCT. Allo-SCT should be considered as a treatment option in young relapsed patients with high-risk disease features after first-line treatment.     

Increased uterine arterial pressure and contractility of perfused swine uterus after treatment with serum from pre-eclamptic women and endothelin-1

The present study was designed to examine the effects of ET-1 (endothelin-1) and serum from PE (pre-eclamptic), HP (healthy pregnant) and HNP (healthy non-pregnant) women on uterine arterial perfusion pressure and uterine contractility. Swine uteri (n = 25) were perfused for a period of up to 11 h, with the aim being to preserve a viable organ. Various concentrations of ET-1 as well as serum from PE, HP and HNP women (n = 10 per group) were administered to the perfused swine uteri and IUP (intrauterine pressure) and IAP (intra-arterial pressure) were recorded. ET-1 produced dose-dependent increases in IUP and IAP. The ET-1 concentration in serum was higher in serum from PE women than in HP and HNP women (P > 0.05). Administration of all serum samples had a contractile effect on the swine uterus, with the greatest effect being seen in HNP women (12.8 +/- 5.3 mmHg), followed by PE (9.06 +/- 4.2 mmHg) and HP (6.1 +/- 4.1 mmHg) women. Statistically significant differences were observed between HNP and PE women (P = 0.048), and PE and HP women (P = 0.021). Increases in IAP following administration of serum from PE women (48.8 +/- 20.0 mmHg) were significantly higher (P = 0.024) compared with the effect of serum from HP women (28.4 +/- 13.7 mmHg). In conclusion, the findings show that serum from PE women has significant vasoconstrictive and oxytocic effects compared with serum from HP women. In pre-eclampsia, the balance between vasorelaxing and vasoactive substances is disturbed.     

Indirect estimation of pediatric Health Related Limits for serum thyrotropin using the ADVIA Centaur analyzer

OBJECTIVES: To determine pediatric reference values for thyrotropin using Advia Centaur analyzer. DESIGN AND METHODS: The study was conducted in a large regional hospital on TSH results obtained from 5741 females and 4332 males aged 0-17 years. After the exclusion of the results outside 4 standard deviations, we calculated the Health Related Limits (HRLs) following the indirect Kairisto's procedure and using the software GraphROC. RESULTS: The lower HRL of TSH concentration was 0.70 mU/L in the years 0-11 and 0.50 mU/L in the following years. The upper TSH HRL was 6.9 mU/L in males vs. 5.7 mU/L in females in the first year and 6.7 mU/L vs. 5.3 in the period 1-2 years. The upper HRLs in females and males were similar in the following years and the upper HRL in the 13-17 years class was 3.8 mU/L. CONCLUSIONS: The indirect methods appear reliable for calculating the pediatric HRLs for TSH.     

Myocardial and vascular dysfunction in systemic sclerosis: the potential role of noninvasive assessment in asymptomatic patients

Systemic sclerosis (SSc) is a multi-system disorder characterized by widespread vascular lesions and fibrosis of skin and distinct internal organs. The aim of the present study was to analyze possible associations of left ventricular (LV) myocardial function with coronary flow reserve (CFR) and endothelial function in asymptomatic patients with SSc. Thirty healthy subjects and 33 age- and sex-comparable asymptomatic SSc patients underwent standard Doppler Myocardial Imaging, Strain Rate (SR) Imaging of interventricular septum (IVS) and LV lateral wall, transthoracic CFR of left anterior descending coronary vessel, and brachial artery vasodilatation measurement. In SSc patients, LV myocardial early diastolic peak velocity, peak systolic SR and strain were both reduced in basal and middle IVS, and in basal and middle LV lateral wall (p<0.001). In addition, both CFR (p<0.0001) and endothelial flow-mediated dilatation (p<0.001) were significantly lower in SSc patients. By stepwise forward multivariate analyses, CFR (p<0.001) and endothelial function (p<0.001) were powerful independent determinants of middle LV strain of SSc patients. In conclusion, SR Imaging, transthoracic CFR and brachial artery flow-mediated dilatation are valuable non-invasive and easy-repeatable tools for detecting early LV myocardial and vascular involvement caused by SSc.     

Sexual dimorphism in thyroid function and type 1 iodothyronine deiodinase activity in pre-pubertal and adult rats

Iodothyronine deiodinase activities are regulated by sex steroids; however, the mechanisms underlying the reported sexual dimorphism are poorly defined. In the present report, we aimed to investigate whether type 1 deiodinase (D1) sexual dimorphism exists early in sexual development by studying pre-pubertal male (Pm) and female (Pf) rats, as well as adult controls (C) and gonadectomized male and females rats. Adult male Wistar rats were studied 21 days after orchiectomy (Tex), and adult females were studied 21 days after ovariectomy (Ovx), and after estradiol benzoate (Eb) replacement. Serum total triiodothyronine (T3) was higher in pre-pubertal (P) rats than in the matching adults, with no difference between genders, although in adult males T3 was significantly lower than in females. There were no sex or age differences in serum total T4. Serum TSH in pre-pubertal (P) rats was within the adult female range, and both were significantly lower than in adult males. D1 activity in liver was greater in Pm than in Pf. In adult females, liver D1 activity was lower, while in adult males it was higher than in P rats. The same pattern of D1 activity was found in kidney. In thyroid and pituitary, D1 activity was similar in Pm, Pf, and adult females, which were all significantly lower than in the adult male. There were no differences in serum T3 and T4 between C and Tex males, but serum TSH was significantly decreased in Tex rats. Hepatic and renal D1 activities were lower in Tex than in C, but no changes were detected in thyroid and pituitary. In Ovx females, T3 was significantly lower than in the C group. Serum T4 was significantly decreased by estradiol replacement therapy in Ovx rats, in both doses used, whereas TSH was unchanged. Eb replacement increased liver and thyroid D1 activity, but in the kidney, only the highest estradiol dose promoted a significant D1 increase. In conclusion, in males, hepatic and renal D1 activity appears to be significantly influenced by gonadal hormones, in contrast to females, in which only exogenous Eb treatment stimulated D1 activity. The comparison between pre-pubertal and adult rats suggests that serum T3 is not the main regulator of D1 activity, and other factors, besides T3 and gonadal hormones, can modulate D1 activity during murine maturation.