Comparison between a second and a third generation parathyroid hormone assay in hemodialysis patients

Objective

Third generation parathyroid hormone (PTH) assays are new generation assays that do not recognize the PTH_7–84 fragment whereas second generation assays detect both PTH_1–84 and PTH_7–84 fragments. Despite the excellent correlation between both assays in chronic renal failure (CRF) subjects, the mean PTH levels are typically 50% lower with the third compared to the second generation assays. The assessment of third generation PTH assays has not been extensively studied in hemodialysis subjects. The purpose of our study was to compare a third generation PTH assay to a second generation one in a population of hemodialysis subjects.

Materials and methods

92 haemodialysis subjects (36 women and 56 men) with a mean age of 67±12.9 years were included in this study. Anthropometric and clinical parameters (Body Mass Index (BMI) and blood pressure) were measured. Second and third generation PTH assays (Cis biomedical and Diasorin respectively) were performed in each subject. In addition, the following biochemical tests were measured: 25-hydroxyvitamin D (25-(OH)D), 1,25-hydroxyvitamin D (1,25-(OH)₂D), crosslaps and alkaline phosphatase.

Results

The mean second and third generation PTHs are respectively 211±205 pg/ml and 151±164 pg/ml. The mean third generation PTH values are 28.4% lower compared to the second generation ones. Both methods are strongly correlated (r = 0.923, p < 0.001). This correlation persisted without any significant difference after controlling for gender, age, BMI and Blood Pressure. However, the difference between both methods increases when baseline PTH increases. Each of the second and third generation method is significantly correlated with hemodialysis duration (p < 0.01), crosslaps (p < 0.001), alkaline phosphatase (p < 0.05), but not with age, BMI, Blood Pressure, 25-(OH)D or 1,25-(OH) ₂D levels.

Conclusion

Our results show that both second and third generation PTH methods are strongly correlated in hemodialysis patients mainly when PTH values are low. However, the difference between both methods increases when PTH values are high. More research is needed to establish which method is the gold standard when PTH values are high.     

A 6-month follow-up of intermittent levosimendan administration effect on systolic function, specific activity questionnaire, and arrhythmia in advanced heart failure

BackgroundLevosimendan (LS) improves cardiac contractility without increasing myocardial oxygen demand. We administrated LS on a monthly intermittent 24-hour protocol and evaluated the clinical effect after 6 months in a randomized, open, prospective study.Methods and ResultsFifty patients (age 45–65 years) with LV systolic dysfunction and New York Heart Association (NYHA) III or IV were randomized in 2 groups. LS group (n = 25) was compared with a control group (n = 25) matched for sex, age, and NYHA class. LS was given monthly on a 24-hour intravenous protocol for 6 months. Patients were evaluated by specific activity questionnaire (SAQ) and echocardiography (ECHO) before and 3 to 5 days after last drug administration, whereas 24-hour Holter recording was performed before and during last drug administration. Patients in LS and control group had same baseline SAQ, ECHO, and Holter parameters. At the end of the study, a larger proportion of patients in the levosimendan group reported improvement in symptoms (dyspnea and fatigue) (65% versus 20% in controls, P < .01). After 6 months, the LS group had a significant increase in LV ejection fraction versus controls (28 ± 7 versus 21 ± 4 %, P = .003), LV shortening fraction (15 ± 3 versus 11 ± 3 %, P = .006) and a decrease in mitral regurgitation (1.5 ± 0.8 versus 2.7 ± 0.6, P = .0001). There was no increase in supraventricular or ventricular beats or supraventricular tachycardia and VT episodes in LS group, compared with controls. Two patients from the LS group died in the 6-month follow-up period, compared with 8 patients in the control group (8% versus 32%, P < .05).ConclusionsA 6-month intermittent LS treatment in patients with decompensated advanced heart failure improved symptoms and LV systolic function.     

Influenza vaccination and risk of mortality among adults hospitalized with community-acquired pneumonia

BACKGROUND: Influenza vaccination has been shown to reduce illness and all-cause mortality in vulnerable populations through the prevention of influenza infection. Attenuation of the severity of illness by vaccination has been reported for respiratory tract infections due to bacterial pathogens and would represent an important additional health benefit of influenza vaccination. We evaluated the impact of prior influenza vaccination on in-hospital mortality and other health outcomes among hospitalized adults with community-acquired pneumonia (CAP). METHODS: Consecutive individuals hospitalized with CAP during "influenza season" (November to April, 1999-2003) at hospitals operated by Tenet HealthCare were identified using a database constructed to improve quality of patient care. Associations between vaccination status and all-cause in-hospital mortality were evaluated using logistic regression models. RESULTS: Among 17 393 adults hospitalized with CAP during the study period, 1590 (19% of those with recorded vaccine status) had a history of influenza vaccination in the current or most recent influenza season. Vaccine recipients were less likely to die in hospital of any cause than individuals without vaccination (odds ratio, 0.30; 95% confidence interval, 0.22-0.41). These effects remained significant after adjustment for the presence of comorbid illnesses and pneumococcal vaccination (adjusted odds ratio for death, 0.61; 95% confidence interval, 0.43-0.87) and under widely varying assumptions about individuals with missing vaccination status. CONCLUSIONS: Prior influenza vaccination was associated with improved survival in hospitalized patients with CAP during influenza season. This observation, if confirmed by other studies, would represent an important additional benefit of enhanced influenza vaccine coverage.     

Complete response in myeloma extends survival without, but not with history of prior monoclonal gammopathy of undetermined significance or smouldering disease

Complete response (CR) is still considered an important surrogate marker for outcome in multiple myeloma (MM). Long-term survival after transplantation, however, has been observed in a substantial proportion of patients who never achieved CR. The tandem transplant trial, Total Therapy 2, enrolled 668 patients, who were randomised up-front to thalidomide (THAL) or no THAL; 56 patients were identified as having had, for at least 6 months prior to initiation of therapy, monoclonal gammopathy of undetermined significance (MGUS, n = 21), smouldering MM (SMM, n = 22) or solitary plasmacytoma of bone (SPC, n = 13). The clinical characteristics and outcomes of patients with such 'evolved' MM (E-MM) and of those with 'unknown' prior history (U-MM) were compared. Fewer patients with MGUS/SMM-E-MM had anaemia or renal failure; CR was lower (22% vs. 48%) but 4-year estimates of event-free survival (54% vs. 56% with U-MM) and overall survival (65% vs. 70% with U-MM) were similar to those with SPC-E-MM or U-MM. In the latter group, achieving CR was associated with prolonged survival. In comparison with U-MM, E-MM evolved from MGUS/SMM was associated with lower CR rate without adversely affecting survival. In contrast, CR was an independent favourable feature for survival in U-MM.     

Related F-box proteins control cell death in Caenorhabditis elegans and human lymphoma

Cell death is a common metazoan cell fate, and its inactivation is central to human malignancy. In Caenorhabditis elegans, apoptotic cell death occurs via the activation of the caspase CED-3 following binding of the EGL-1/BH3-only protein to the antiapoptotic CED-9/BCL2 protein. Here we report a major alternative mechanism for caspase activation in vivo involving the F-box protein DRE-1. DRE-1 functions in parallel to EGL-1, requires CED-9 for activity, and binds to CED-9, suggesting that DRE-1 promotes apoptosis by inactivating CED-9. FBXO10, a human protein related to DRE-1, binds BCL2 and promotes its degradation, thereby initiating cell death. Moreover, some human diffuse large B-cell lymphomas have inactivating mutations in FBXO10 or express FBXO10 at low levels. Our results suggest that DRE-1/FBXO10 is a conserved regulator of apoptosis.     

Hemisphere-hand interactions for the matching of letters

Abstract

Young, middle aged, and older subjects were given a Posner-type physical-name matching task, in which stimuli were presented to one or both hemispheres, and a simple discrimination reaction time (DRT) task. Reaction time differed between young and middle aged groups for both tasks with shorter RT for the DRT task. Reaction time for the older group did not differ significantly from that of the middle aged group for either task, although the reaction time for the older group was longer. Reaction time was faster for all age groups when Stimulus 1 and Stimulus 2 were presented to different hemispheres for the matching task than when both stimuli were presented to the same hemisphere. Ipsilateral finger responses (hand relative to hemisphere) were slower than contralateral responses but this was true only with regard to the visual field of presentation for stimulus 2. These data indicate that sharing of information between hemispheres under certain circumstances increases the efficiency of information processing relative to that observed with unilateral visual half-field (hemisphere) presentations and that hand or finger response relative to visual field of presentation is an important factor which must be controlled and examined relative to visual field of presentation.     

Analysis of SAA1 gene polymorphisms in the Greek population: rheumatoid arthritis and FMF patients relative to normal controls. Homogeneous distribution and low incidence of AA amyloidosis

Objective. To address whether or not the rarity of amyloidosis in Greek patients with rheumatoid arthritis (RA) is related to specific alleles of single nucleotide polymorphisms (SNPs) in the 5′-flanking region and the exon 3 of the SSA1 gene.

Methods. The genotypes of the ?13T/C SNP in the 5′-flanking region of the SAA1 gene and the two SNPs within exon 3 of SAA1 (2995C/T and 3010C/T polymorphisms) were determined in 88 Greek patients with RA, 14 patients with familial Mediterranean fever (FMF) and 110 healthy controls. Linkage disequilibrium and haplotype frequencies involving ?13T/C, 2995C/T and 3010C/T in these populations were tested and estimated, respectively.

Results. The genotypic distribution and allelic frequencies were similar in all groups tested. SNPs 2995 and 3010 were in linkage disequilibrium for all study populations (p < 0.05), whereas SNP ?13 was not in linkage disequilibrium with either 2995 or 3010 (p ≥ 0.05). Two major haplotypes presented in all patients with RA and FMF and controls: ?13C; 2995T; 3010C (?13C; α) and ?13C; 2995C; 3010T (?13C; β). The ?13T allele was linked with the γ haplotype in Greek patients with RA and controls. The frequency of the ?13T allele was found to be very rare in all groups tested.

Conclusions. In conclusion, the rarity of the putative amyloidogenic ?13T allele in Greek populations may be related to low prevalence of AA amyloidosis development in Greek RA patients.     

Analysis of SAA1 gene polymorphisms in the Greek population: rheumatoid arthritis and FMF patients relative to normal controls. Homogeneous distribution and low incidence of AA amyloidosis.

OBJECTIVE: To address whether or not the rarity of amyloidosis in Greek patients with rheumatoid arthritis (RA) is related to specific alleles of single nucleotide polymorphisms (SNPs) in the 5'-flanking region and the exon 3 of the SSA1 gene. METHODS: The genotypes of the -13T/C SNP in the 5'-flanking region of the SAA1 gene and the two SNPs within exon 3 of SAA1 (2995C/T and 3010C/T polymorphisms) were determined in 88 Greek patients with RA, 14 patients with familial Mediterranean fever (FMF) and 110 healthy controls. Linkage disequilibrium and haplotype frequencies involving -13T/C, 2995C/T and 3010C/T in these populations were tested and estimated, respectively. RESULTS: The genotypic distribution and allelic frequencies were similar in all groups tested. SNPs 2995 and 3010 were in linkage disequilibrium for all study populations (p < 0.05), whereas SNP -13 was not in linkage disequilibrium with either 2995 or 3010 (p > or = 0.05). Two major haplotypes presented in all patients with RA and FMF and controls: -13C; 2995T; 3010C (-13C; alpha) and -13C; 2995C; 3010T (-13C; beta). The -13T allele was linked with the gamma haplotype in Greek patients with RA and controls. The frequency of the -13T allele was found to be very rare in all groups tested. CONCLUSIONS: In conclusion, the rarity of the putative amyloidogenic -13T allele in Greek populations may be related to low prevalence of AA amyloidosis development in Greek RA patients.