Association of high-sensitivity assayed troponin I with cardiovascular phenotypes in the general population: the population-based Gutenberg health study

Background

Aim of the study was to analyze the correlation of high-sensitivity assayed troponin I with cardiac and vascular structure and function in a large population-based cohort.

Methods

In a sample of 4,139 subjects (2,099 men, 2,040 women, age 35–74 years) from the population-based Gutenberg Health Study, troponin I was measured with a high-sensitivity assay that had a limit of detection of 1.9 pg/mL.

Results

In the study cohort, 3,405 subjects had detectable troponin I concentrations [82.3 % overall, 89.9 % men (N = 1,888), 74.4 % women (N = 1,517)]. All analyses were adjusted for age. The strongest correlate between detectable troponin I and measures of cardiac phenotypes was observed for left ventricular mass (p < 0.001) and left ventricular end-diastolic diameter (p < 0.001) for both, women and men. Left ventricular ejection fraction was inversely correlated with troponin I (p value <0.001 in men and 0.0013 in women), also measures of diastolic dysfunction as represented by Tei index and E/E′ correlated with detectable troponin I concentrations (p < 0.001 for both gender). With respect to vascular structure and function, troponin I correlated with mean intima-media thickness of the carotid artery (p < 0.001 in men and p = 0.013 in women) but showed only borderline correlation with measures of vascular function represented by flow-mediated dilation (p = 0.05 in women and p = 0.018 in men) and arterial stiffness.

Conclusions

Troponin I assessed by a high-sensitivity assay correlated with measures of left ventricular hypertrophy and systolic and diastolic function, whereas its correlation with vascular phenotypes was only of weak magnitude.     

Nerve growth factor-dependent activation of trkA receptors in the human ovary results in synthesis of follicle-stimulating hormone receptors and estrogen secretion

CONTEXT: Previous studies showed that nerve growth factor (NGF) induces the expression of functional FSH receptors (FSHR) in preantral follicles of the developing rat ovary. OBJECTIVE: The objective of this study was to determine whether NGF can affect granulosa cell (GC) function in human periovulatory follicles using intact human ovaries and isolated human GCs. PATIENTS AND INTERVENTIONS: Human GCs were obtained from in vitro fertilization patients and normal ovaries from women with elective pelvic surgery for nonovarian indications. Results: In normal ovaries, NGF and trkA (NGF's high-affinity receptor) were detected by immunohistochemistry in GCs of preantral and antral follicles. NGF and trkA are also present in thecal cells of antral follicles. Both freshly collected and cultured GCs contained immunoreactive NGF and trkA in addition to their respective mRNAs. Human GCs respond to NGF with increased estradiol (E(2)) secretion and a reduction in progesterone output. Exposure of human GCs to NGF increased FSHR mRNA content within 18 h of treatment, and this effect was blocked by the trk tyrosine kinase blocker K-252a. Also, cells preexposed to NGF released significantly more E(2) in response to hFSH than cells not pretreated with the neurotropin, showing that the NGF-induced increase in FSHR gene expression results in the formation of functional FSHRs. CONCLUSIONS: These results suggest that one of the functions of NGF in the preovulatory human ovary is to increase the secretion of E(2) while preventing early luteinization via an inhibitory effect on progesterone secretion. NGF stimulates E(2) secretion both directly and by increasing the formation of FSHRs.     

Norepinephrine release in the immature ovary is regulated by autoreceptors and neuropeptide-Y.

Experiments were undertaken to study the role that neuropeptide-Y (NPY) and adrenergic autoreceptors may play in the regulation of norepinephrine (NE) release from the rat ovary. Ovaries from 28- to 32-day-old rats were preincubated with [3H]NE, and the release of the recently taken up catecholamine in response to electric field stimulation was assessed. The release was strictly dependent on the presence of extracellular calcium and decreased when the frequency of stimulation was increased. This drop in [3H]NE release was significantly reversed by exposure of the ovaries during stimulation to yohimbine, a selective alpha 2-adrenoreceptor blocker. The existence of prejunctional alpha 2-adrenergic autoreceptors in ovarian nerves was further suggested by the ability of exogenous NE to mimic the inhibitory effect of high frequency stimulation. NPY inhibited by 40% the release of [3H]NE induced by electrical stimulation. The specificity of this effect and its prejunctional nature were demonstrated by the finding that avian pancreatic polypeptide, a structural homolog of NPY that is not recognized by prejunctional NPY receptors of the Y2 subtype, failed to alter the induced release of [3H]NE. Neither NPY, avian pancreatic polypeptide, nor peptide-YY, another member of the pancreatic polypeptide fold family, altered progesterone or estradiol secretion from whole ovaries or granulosa cells in culture, suggesting that NPY (and its structural homologs) does not directly affect ovarian steroidogenesis. The results suggest that 1) the release of NE from ovarian sympathetic nerves is subjected to a dual modulatory influence provided by NE itself and NPY; and 2) this regulatory effect is exerted via specific prejunctional receptors. Such NE/NPY actions are likely to regulate the availability of NE to its postsynaptic receptors during ovarian development and adult function. The fact that NPY is mostly released during high frequency stimulation raises the possibility of NPY involvement in ovarian dysfunctions associated with situations of enhanced sympathetic discharge, such as strenuous exercise and psychogenic amenorrhea.     

Short‐ and long‐term results of a programme for the prevention of readmissions and mortality in patients with heart failure: Are effects maintained after stopping the programme?

The objective of the study was to evaluate whether improvements obtained during an intervention programme were maintained after the programme was stopped. 153 patients discharged with a diagnosis of heart failure (HF) were randomized to either usual care or an intervention programme, which included patient education, consultation with the cardiologist and monitoring in the Heart Failure Unit. After an average period of 16+/-8 months, the intervention programme was stopped. One year later, all the patients were re-examined to assess HF readmissions, all-cause mortality, quality of life, and prescribed medical treatment. During the 16+/-8-month treatment period, patients in the intervention group had a lower rate of HF readmissions (17% vs. 51%, p<0.01), less all-cause mortality (13% vs. 27%, p=0.03), improvement in quality of life (1.5+/-0.8 vs. 1.9+/-1, p=0.03) and optimisation of medical treatment was achieved. One year after stopping the intervention, there was no difference in HF readmissions (28% vs. 25%, p=0.72), all-cause mortality (14% vs. 17%, p=0.64) and quality of life (1.7+/-0.9 vs. 1.8+/-1, p=0.24) between the groups. Survival and the probability of not being readmitted due to HF were similar in both groups. There was also a reduction in the use of beta-blockers and spironolactone in the intervention group. CONCLUSIONS: The positive effects of an intervention programme are clearly reduced when it is stopped, due to less strict control of the patients and a decrease in the use of drugs with proven efficacy in HF.     

Chronic zinc deficiency induces an antioxidant adaptive response in rat lung

Few studies are available about the role of dietary zinc (Zn) in respiratory diseases. Adult male rats were divided into 2 groups and fed respectively a moderate Zn-deficient diet and a Zn-adequate control diet. In lung tissue at 2 months, thiobarbituric acid-reactive species (TBARS), total glutathione, glutathione disulfide, protein carbonyls, metallothionein, and the activities of glutathione peroxidase (GPx), catalase, CuZn-superoxide dismutase (CuZnSOD) and glucose-6-phosphate dehydrogenase (G-6-PDH) were increased, but protein thiols decreased. In lung tissue at 4 months, TBARS, metallothionein, and the activities of CuZnSOD, Mn-superoxide dismutase (MnSOD) increased. The activities GPx, catalase, G-6-PDH were lower than control group. The changes were accompanied by histological alterations in Zn-deficient lung. The results provide evidence of the pro-oxidative effects of Zn-deficiency in lung, and suggest that the time of treatment play a key role in determining lung susceptibility to oxidative stress.     

Nerve growth factor induces the expression of functional FSH receptors in newly formed follicles of the rat ovary

The neurotrophin nerve growth factor (NGF) and its two membrane-anchored receptors are expressed in the developing ovary before the organization of the first primordial follicles. In the absence of NGF, the growth of primordial follicles is retarded, indicating that NGF contributes to facilitating early follicular development. The present experiments were undertaken to determine whether NGF can also be involved in the differentiation process by which ovarian follicles become responsive to gonadotropins. Treatment of 2-d-old rat ovaries in organ culture with NGF increased FSH receptor (FSHR) mRNA within 8 h of exposure. This effect was cAMP-independent but additive to the cAMP-mediated increase in FSHR gene expression induced by either forskolin or vasoactive intestinal peptide, a neurotransmitter previously shown to induce FSHR formation in neonatal rat ovaries. After NGF treatment, the ovary acquired the capacity of responding to FSH with cAMP formation and preantral follicular growth, indicating that exposure to the neurotrophin resulted in the formation of biologically active FSHRs. Quantitative measurement of FSHR mRNA demonstrated that the content of FSHR mRNA is reduced in the ovaries of mice carrying a null mutation of the NGF gene. These results indicate that one of the functions of NGF in the developing ovary is to facilitate the differentiation process by which early growing follicles become gonadotropin-dependent during postnatal life, and that it does so by increasing the synthesis of FSHRs.     

Prevalence of comorbidities in rheumatoid arthritis and evaluation of their monitoring in clinical practice: the spanish cohort of the COMORA study

Objectives

To describe the prevalence of comorbidities in patients with RA in Spain and discuss their management and implications using data from the Spanish cohort of the multinational study on COMOrbidities in Rheumatoid Arthritis (COMORA).

Hepatitis B Infection and Association with Other Sexually Transmitted Infections Among Men Who Have Sex with Men in Peru

To assess the epidemiology of hepatitis B virus (HBV) infection among men who have sex with men (MSM) in Peru, we evaluated the prevalence and associated risk factors for HBV serologic markers among participants of a HIV sentinel surveillance conducted in 2002–2003. The standardized prevalences for total antibodies to hepatitis B core antigen (anti-HBc) and hepatitis B surface antigen (HBsAg) were 20.2% and 2.8%, respectively. Individuals with human immunodeficiency virus (HIV-1) infection had significantly higher anti-HBc (44.3% versus 19.3%) and HBsAg (9.5% versus 2.3%) prevalences than uninfected men. Increasing age (adjusted odds ratio [AOR] = 1.06), versatile sexual role (AOR = 1.59), sex in exchange for money/gifts (AOR = 1.58), syphilis (AOR = 1.74), HIV-1 infection (AOR = 1.64), and herpes simplex virus type 2 (HSV-2, AOR = 2.77) infection were independently associated with anti-HBc positivity, whereas only HIV-1 infection (AOR = 3.51) and generalized lymph node enlargement (AOR = 3.72) were associated with HBsAg positivity. Pre-existing HBV infection is very common among Peruvian MSM and was correlated with sexual risk factors. MSM in Peru constitute a target population for further HBV preventive and treatment interventions.     

Detection of the nucleophosmin gene mutations in acute myelogenous leukemia through RT-PCR and polyacrylamide gel electrophoresis

Objectives: Mutations in the C‐terminal region of the nucleophosmin (NPM1) gene occur in approximately 60% of acute myeloid leukemia (AML) cases with normal karyotype and represent the most common genetic lesion presently known in this disease. Because of their frequency and favorable impact on prognostic outcome, screening for this aberration is currently recommended in routine diagnostic characterization of AML. Several techniques enabling to detect NPM1 mutation have been reported, but all require sophisticated equipment, which represent an obstacle particularly in countries with limited resources. Methods: We designed an RT‐PCR strategy to amplify NPM1 exon 12 followed by electrophoresis and fragment visualization on polyacrylamide gels to discriminate a 4–5 bp size difference resulting from mutations in this gene. A hemi‐nested method was designed to increase sensitivity for the study of minimal residual disease (MRD). Results: The assay enabled specific detection of NPM1 mutations in 12/36 patients. A 10^?2 sensitivity level was obtained using one amplification round, while the hemi‐nested PCR approach yielded a 10^?5 sensitivity level, therefore proving useful to assess MRD in patients carrying the mutation. The results were independently validated in 24 AML cases by sequencing analysis. Conclusions: This simple and low‐cost assay may integrate diagnostic work‐up of AML and could be used for assessment of response to therapy in patients with NPM1 mutations.     

Cord blood transplants supported by co-infusion of mobilized hematopoietic stem cells from a third-party donor

This open label clinical study provides updated evaluation of the strategy of single unit cord blood transplants (CBTs) with co-infusion of third-party donor (TPD) mobilized hematopoietic stem cells (MHSC). Fifty-five adults with high-risk hematological malignancies, median age 34 years (16-60 years) and weight 70 kg (43-95 kg), received CBTs (median 2.39 x 10(7) total nucleated cell (TNC) per kg and 0.11 x 10(6) CD34+ per kg) and TPD-MHSC (median 2.4 x 10(6) CD34+ per kg and 3.2 x 10(3) CD3+ per kg). Median time to ANC and to CB-ANC >0.5 x 10(9)/l as well as to full CB-chimerism was 10, 21 and 44 days, with maximum cumulative incidences (MCI) of 0.96, 0.95 and 0.91. Median time to unsupported platelets >20 x 10(9)/l was 32 days (MCI 0.78). MCI for grades I-IV and III-IV acute GVHD (aGVHD) were 0.62 and 0.11; 12 of 41 patients (29%) who are at risk developed chronic GVHD, becoming severely extensive in three patients. Relapses occurred in seven patients (MCI=0.17). The main causes of morbi-mortality were post-engraftment infections. CMV reactivations were the most frequent, their incidence declining after the fourth month. Five-year overall survival and disease-free survival (Kaplan-Meier) were 56 % and 47% (63% and 54% for patients 相似文献