Age Groups Of Healthy Subjects Research Articles

Safety and immunogenicity of inactivated hepatitis-A vaccine developed by Human Biologicals Institute in two age groups of healthy subjects: A phase I open label study

BackgroundHepatitis-A is an acute viral infection of the liver. Hepatitis-A virus has worldwide spread and is endemic in India. Though the disease is self-limiting in most cases, outbreaks are reported frequently from both developing and developed countries of the world. Severity and fatality occur more among infected symptomatic adults. The infection can be prevented with proper and timely immunization. This phase I, single arm, open label, multicenter trial was designed to assess the safety and immunogenicity of the inactivated hepatitis-A vaccine developed by Human Biologicals Institute when administered in a single dose in two age groups of healthy subjects. MethodsThis study was carried out in 55 subjects in two healthy age groups at two centers in India. Group A included subjects of 19–49 years and group B subjects of 12–18 years of age. Enrolled subjects received a single dose of inactivated hepatitis A vaccine. Blood samples were collected at baseline and 4–6 weeks after vaccination. Safety was assessed by collection and analysis of data on solicited and unsolicited adverse events and immunogenicity was assessed by estimating the seroconversion rate, seroprotection rate and the geometric mean titres of antibodies. ResultsAmong the 55 subjects enrolled, 15 reported adverse events. No serious adverse event was reported. Pain at the injection site was the lone local adverse event. Systemic adverse events reported in Group A were: fatigue, headache, diarrhoea, fever, anorexia, nausea and upper respiratory tract infection, whereas there was no systemic event reported in Group B. There was 100% seroconversion and seroprotection and significant rise in antibody titre levels were observed in both the groups post vaccination. ConclusionsThis study found HBI inactivated hepatitis-A vaccine to be safe and highly immunogenic when administered as a single dose in adolescent and adult subjects.

Influence of the age factor on pre-mild cognitive impairment

Pre-Mild Cognitive Impairment (PreMCI) is characterized by patients’ complaints of memory impairment and/or other cognitive functions. In elderly and senile age, PreMCI can be a predictor of the development of more significant cognitive defects up to the development of dementia. The study was aimed at the analysis of the neuropsychological characteristics of patients with PreMCI in dependence on their age. Materials and methods . The results of the examination of 547 patients (159 men and 388 women) in the age groups of 45–59 years old, 60–74 years old and 75–89 years old were analyzed in comparison to 104 healthy subjects with the same age characteristics who did not complain of cognitive functions’ impairment. The study included clinical research and the use of scales and questionnaires set evaluating cognitive functions. Results . Significant differences were detected between patients with PreMCI and healthy subjects of middle and old age in most neuropsychological tests. Patients over 75 years old differed from healthy ones only in the clock drawing test and immediate reproduction of 12 words test. Most significant difference in neuropsychological tests in different age groups of healthy subjects was impairment in executive functions and the index of the 12-word immediate reproduction test. Patients with PreMCI had a deterioration of divided-attention measure indicators, executive and language functions, and constructional praxis, while in memory tests no significant dynamics was detected. Conclusion . A broader spectrum of cognitive functions’ defects is detected in patients with PreMCI compared to healthy ones. At the same time, memory impairment is a fixed condition, and is not essentially dependent on age.

Age-related changes in diastolic function in children: Echocardiographic association with vortex formation time.

This study aims to understand the age-related changes in vortex formation time (VFT) index in children, and thus, describe the ranges of VFT in different pediatric age groups with the ultimate goal of assessment of diastolic function. Transthoracic echocardiograms in healthy (n=84) subjects from birth to 20years were analyzed to compute VFT and diastolic performance. LV apical and short-axis views were used. Three separate measurements were performed, and the mean was used to derive VFT and other indices. Statistical comparisons were made amongst the groups, stratified by age. Vortex formation times in neonates (median 1.79, interquartile range 1.31-1.92) and infants (1.38, 1.07-1.72) were found to be significantly lower (P<.05) than the older age groups (1-5years 2.47, 1.87-2.94, 5-10years 2.18, 1.89-2.53, 10-20years 2.34, 1.84-2.96). The changes in VFT correlate to the changes in diastolic function in children. Our results show that unlike adults, VFT changes along with the growth-related myocardial adaptations in children, and its range may be used to evaluate diastolic function. The present study is the first to test the significance of the trans-mitral VFT in children by comparing different age groups of healthy subjects.

Age-related changes in saccadic eye movements in healthy subjects and patients with Parkinson’s disease

Age-related changes in characteristics of saccadic eye movements (latency, duration and percentage of multistep saccades) in healthy subjects and patients with Parkinson's disease were evaluated. Healthy volunteers were divided into 6 age groups (17-20 years, 21-30 years, 31-40 years, 41-50 years, 51-60 years, 61-75 years), parkinsonian patients into 3 age groups (41-50 years, 51-60 years, 61-75 years). According to our data, saccade characteristics depend upon age in both healthy subjects and parkinsonian patients. In healthy volunteers the percentage of multistep saccades and the mean saccade latency increase significantly after the age of 60. Values of these characteristics in patients with Parkinson's disease significantly exceed the values in the corresponding age groups of healthy subjects. The "disease" factor (MANOVA) has a greater influence on saccade latency and percentage of multistep saccades then the "age" factor. The duration of single saccades depends on age to a smaller extent and does not change in patients with Parkinson's disease. The peculiarities of neurodegenerative processes during normal aging and aging with Parkinson's disease are discussed.

Folate and cobalamin levels as determinants of plasma homocysteine in different age groups of healthy controls and psychogeriatric patients.

Homocysteine (Hcy) is the demethylated derivate of methionine and can be metabolized by two pathways. It is either catabolized by the transulfuration pathway to cysteine or remethylated to methionine mainly by the folate- and cobalamin-dependent enzyme methionine synthase. Previous findings suggest that folate is the most important vitamin determinant of plasma total homocysteine (tHcy) concentration but also that the relation between plasma tHcy levels and levels of cobalamin and folate in the circulation might differ in different populations. In the present study, we have analyzed these parameters in different age groups of healthy subjects and psychogeriatric patients, who are known to have increased plasma tHcy. The present study shows that serum cobalamin concentration is a more important determinant of plasma tHcy concentration than blood folate concentration in the age groups <65 years in both psychogeriatric patients and control subjects, whereas with increasing age blood folate concentration becomes the most important vitamin determinant. The findings of increased plasma tHcy with folate being the main vitamin determinant in the oldest age groups of patients and controls, suggest that tissue levels of folate in elderly subjects are too low and that vitamin supplementation should be given.

Increased intracortical inhibition in middle-aged humans; a study using paired-pulse transcranial magnetic stimulation

Using single and paired-pulse transcranial magnetic stimulation we compared the cortical excitability in two different age groups of healthy subjects (mean±SD age: 28.5±5.2 vs. 56.1±4.9 years). Motor evoked potentials were recorded from right extensor and flexor carpi radialis muscles. The effect of paired-pulse stimulation was assessed by the ratio conditioned/unconditioned response area with interstimulus intervals of 3 and 13 ms to test for intracortical inhibition and facilitation, respectively. To test the influence of sensory input the experiments were conducted without and with vibration of the extensor carpi radialis muscle. The intracortical inhibition was significantly greater in older subjects; however, during muscle vibration this difference between the two groups vanished. The different effect of vibration favors compensatory mechanisms to be responsible for a different paired-pulse excitability in middle-aged subjects.

The four-compartment models in body composition: Data from a study with dual-energy x-ray absorptiometry and near-infrared interactance on 815 normal subjects

With the aim of studying body composition according to a four-compartment model in different age groups of healthy subjects, total body water (TBW), body fat (BF), lean body mass (LBM), and total-body bone mineral content (TBBMC) were estimated with dual-energy x-ray absorptiometry (DEXA) and near-infrared interactance in 308 normal males and 507 normal females aged 15 to 83 years. Subjects were divided into 5-year groups up to the age of 50, and then into 10-year groups. In both sexes, BF showed a positive correlation with age ( P < .001) and was higher in females aged 40 to 44 compared with younger groups. LBM decreased with age only among males ( P < .05). A similar finding was observed with TBW. TBBMC values did not differ between sexes in the 15- to 19-year-old group, and were greater in males in the remaining age groups. This parameter did not vary among females until menopause, and decreased in the 50- to 59-year-old group ( P < .001) and from the age of 60 onward ( P < .001). Height decreased ( P < .001) and weight increased with age ( P < .001). Both in male and female groups height and weight correlated with TBBMC ( P < .001). When corrected for weight, TBBMC did not vary except in men older than 50, who showed lower values ( P < .005). When corrected for height, TBBMC only changed in women aged 30 to 34 and 35 to 39. After both corrections, sex diferences were minimized except in the case of men older than 50, who showed higher values ( P < .005). LBM and TBW correlated with TBBMC in males only ( P < .001). BF in either sex correlated with TBBMC ( P < .001). TBBMC values decreased in females from the age of 15 years, and a relevant sex difference was observed in the acquisition of bone mass peak.

Cytologic analysis of pericardial effusion complicating extracardiac malignancy

The ratio of the motion due to atria1 systole to the total diastolic AV plane displacement can therefore be considered to represent the contribution of atria1 systole to left ventricular filling. In our study, all but 3 control subjects had an atria1 contribution of 150%. According to Starling’s law of the hearC the ventricular contraction is dependent on the end-diastolic fiber length and pressure. The atrium, by virtue of its active contraction, can modify ventricular end-diastolic pressure and end-diastolic fiber length, and thereby is capable of modifying the performance of the ventricle. In this study, younger subjects showed a relatively mild atria1 systole, compared with older groups, as judged from the decreased ratio between atria1 AV and total AV plane displacement. These findings reflect the phenomenon of decreased left ventricular compliance with advancing age with a concomitant compensatory augmentation of active atria1 emptying as reflected by an increase in atria1 AV plane displacement in older age groups. This was further supported by the finding of a good linear correlation of age with the atria1 contribution to AV plane displacement. Using different techniques, others have also demonstrated a decrease in diastolic function with advanced age.lOyl l The ratio of the height of the “A” wave to the “E” wave in the Doppler velocity curve across the mitral valve is frequently used to express the contribution of atria1 systole to left ventricular filling. With increasing age, this ratio also increases because of a larger contribution of atria1 systole to overall left ventricular filling.rO In this study there was a good linear correlation between A/E waves and the contribution of atria1 AV plane displacement, which further supports the usefulness of the new echocardiographic parameter for the assessment of diastolic function. Right ventricular systolic descent of the AV plane is related to systolic function in a way similar to that of the left ventricle. However, the displacement was significantly greater than left ventricular AV plane displacement. This is in agreement with Rushmer et al** and reflects the predominance of longitudinal shortening of the right ventricular free wall with little shortening of its width. This is probably due to different patterns of muscle structure in the right ventricle. Although the right atria1 AV plane displacement was significantly increased compared with the left atria1 AV plane displacement, the percentage of atria1 contribution to right ventricular filling was quite similar to that of the left ventricle. However, in calculating AV plane displacement of the right ventricular free wall, we probably underestimated the absolute excursion because of a slightly arc-like movement of the recording site, causing a narrow angle with the ultrasound beam. In conclusion, this study provides a simple echocardiographic means of assessing left ventricular diastolic function in a series of healthy subjects. The method is highly reproducible with low inter- and intraobserver variabilities. Normal values of atria1 AV plane displacement in relation to total AV plane displacement for different age groups of healthy subjects provide further information regarding the age-related changes in diastolic function. Further studies, however, are needed to assess its significance, especially in patients with pathologic impairment in diastolic function.

The effect of age on the renal response to PTH infusion.

The renal responses to PTH infusion were compared in two age groups of healthy subjects. Basal nephrogenous cyclic AMP (NcAMP) was higher (1.68 +/- 0.74 vs. 0.97 +/- 0.50 nmol/dl GF; P less than 0.05) and TmPO4/GFR was lower (0.93 +/- 0.21 vs. 1.16 +/- 0.14 mmol/liter; P less than 0.025) in 10 elderly subjects compared with 12 young adults. Creatinine clearance was decreased in the elderly (84.8 +/- 25.7 vs. 144.7 +/- 43.2 ml/min; P less than 0.005) and serum iPTH tended to be increased (0.15 +/- 0.11 vs. 0.11 +/- 0.03 pmol/liter). Following the infusion of 3 IU bPTH/kg bodyweight, no significant differences in delta NcAMP and delta TmPO4/GFR were seen between the groups. When responses were expressed as percentual change of basal level, elderly subjects showed a % NcAMP of 1831 +/- 1200 which was comparable with 2038 +/- 1503% in young adults. However, the percentual change in TmPO4/GFR was significantly higher in elderly persons (24.2 +/- 11.9 vs. 11.9 +/- 8.0%; P less than 0.01). In young subjects, virtually absent TmPO4/GFR responses were found in 3 cases with a relatively low basal TmPO4/GFR (between 0.92 and 0.98 mmol/liter), but these cases showed normal increases in NcAMP. Elderly subjects retained a considerable delta TmPO4/GFR notwithstanding a basal TmPO4/GFR below 0.92 in seven out of 10 cases. These results confirm the existence of a slight increase in parathyroid activity in the elderly. In addition, they suggest an augmented sensitivity of the renal tubule concerning PO4 reabsorption in elderly subjects. It is speculated that this phenomenon is related to the fall in bone mineral retention in senescence and might reflect a defense mechanism against phosphate overload.

Age-related elevation of plasma catecholamine concentration and reduced responsiveness of lymphocyte adenylate cyclase.

Plasma catecholamine (norepinephrine) concentration during upright posture and lymphocyte adenylate cyclase response to the β-adrenergic catecholamine isoproterenol were compared in two age groups of healthy subjects. Compared to subjects between the ages of 19-38 yr, those between 65-88 yr had higher plasma norepinephrine concentrations (353 ± 42 vs. 577 ± 65 pg⁄ml) and reduced lymphocyte adenylate cyclase responsiveness to NaF, isoproterenol, guanyl nucleotide, and isoproterenol in the presence of guanylyl nucleotide. There were important differences between the properties of adenylate cyclase in cells from the aged subjects and those from younger subjects pretreated with norepinephrine in vitro. Pretreated cells had diminished responsiveness to isoproterenol (desensitization), but not to guanylyl nucleotide. Moreover, guanylyl nucleotide restored isoproterenol responsiveness to the desensitized enzyme. Thus, reduced responsiveness of lymphocyte adenylate cyclase from aged subjects was not attributable solely to acutely elevated plasma plasma catecholamine levels The interactions between the guanylyl nucleotide-requiring coupling factors and the catalytic subunits of adenylate cyclase were similar in the two age groups, as evidenced by similar Km values of activation by the nonhydrolyzable GTP analog Gpp[NH]p (guanyl-5-yl imidodiphosphate) and by Hill coefficients of activation near unity. The initial velocity of product formation by adenylate cyclase from the older group was only about half that from the younger group in the presence of Gpp[NH]p. These differences could not be attributed to age-related changes in the distribution of cell types in the leukocyte population. The results suggest that decreases in the concentration of either the guanylyl nucleotide-requiring coupling factors or the catalytic subunits of adenylate cyclase may accompany aging and contribute to the diminished responsiveness of the lymphocyte enzyme. Similar decreases could occur in less accessible catecholamine target tissues as a consequence of human aging.