Important Age-related Differences Research Articles

Biological and psychological differences in the child and adolescent transplant recipient

Solid organ transplantation has become accepted therapy for the treatment of end-stage organ dysfunction in children. As early management of the pediatric transplant recipient has improved, important age-related differences in long-term patient outcomes have become apparent. Late morbidity and mortality can, in most cases, be attributed to the consequences of long-term immunosuppression: graft loss from under-immunosuppression or an increased incidence of cancer, hypertension, renal failure or diabetes from over-immunosuppression. Age-related differences in both biological and psychological factors play an important role in the optimization of therapy in the transplanted child. Important age-related differences have been demonstrated in all phases of pharmacokinetics: absorption, distribution, metabolism and elimination. Information regarding specific age-related pharmacokinetic differences is lacking for many immunosuppressive medications. Further study using physiologically based pharmacokinetic (PBPK) models will lead to more specific recommendations for age-based immunosuppression protocols. Non-adherence is common among solid organ transplant recipients of all ages and the consequences of non-adherence include increased rejection, late graft loss and death. The biological and psychological developmental changes that occur during adolescence place the transplanted adolescent at an even higher risk of non-adherence and poor outcome than other age groups. Further studies to elucidate the importance of both age-related pharmacokinetic and behavioral factors are needed to formulate therapeutic interventions that would improve adherence and patient outcomes.

P.7.015 Anger, anger coping and stress response of events in male and female delinquent adolescents released with warning by police

This study examines resilience and desistance from delinquent behaviours and attempts to identify factors which predict persistent or increased or decreased delinquency between adolescence and early childhood. A sample of 363 young people was obtained from the population of five public institutions in 1987 and 1992. Their delinquent trajectories were described on the basis of legal records. These suggested that resilience is a rare phenomenon and is associated with stable relationships, absence of diagnostic label and good adaptation to the institution. Two axes were identified which can be used to describe the population, the family background and the psychological characteristics of the individual. Information which predicted desistance from a delinquent career was identified by means of a stepwise multiple regression. Analyses were conducted separately for each age group to take account of differences in time after the placement. The results indicated that there are important age-related differences in the characteristics which influence desistance or risk. They also show length of stay in an institution to be a predictor. Desistance from further delinquency seems to depend on the time spent in the residential environment associated with an increase of guilt, an improvement of self-image and of attachment to one or more other people.

A Practice of Anesthesia for Infants and Children, 3rd Edition.

A Practice of Anesthesia for Infants and Children, 3rd Edition.

Age-related trends in pathogen frequency and antimicrobial susceptibility of bloodstream isolates in North America: SENTRY Antimicrobial Surveillance Program, 1997–2000

We report age-related trends in pathogen frequency and antimicrobial susceptibility from 25,745 bloodstream infections (BSI) due to bacterial pathogens reported from medical centres participating in the North American SENTRY Antimicrobial Surveillance Program between January 1997 and September 2000. Staphylococcus aureus, Escherichia coli and coagulase-negative staphylococci (CoNS) were the most common pathogens, together accounting for 55% of all BSI pathogens during this time period. Among nosocomial BSI, CoNS were the most frequently isolated pathogens in infants less than 1 year of age, but S. aureus increased in frequency with increasing age. Among community-onset BSI pathogens, Streptococcus pneumoniae was the most frequently reported pathogen causing BSI in patients aged 1–5, S. aureus among those aged 6–64, and E. coli predominated at the extremes of age (less than 1 year and ≥65 years of age). Among key organism: antimicrobial agent combinations evaluated, oxacillin resistance in S. aureus increased with increasing age; conversely, oxacillin resistance among CoNS was highest among children 5 years of age or younger. Penicillin resistance among S. pneumoniae BSI was highest in children younger than 5 years, while vancomycin resistance among Enterococcus spp. predominated among nosocomial BSI in patients over 50 years of age. Important age-related differences exist in species distribution and antimicrobial susceptibility of pathogens causing BSI. This information should be helpful for clinicians as they consider empirical antimicrobial therapy for patients with suspected BSI across the age continuum.

A new course in age-based medicine at the University Medical Center of Nijmegen.

In 1995 the Medical Faculty of the University Medical Center of Nijmegen revised its curriculum to be more problem-oriented and student-centered. Each of the first four years now consists of ten four-week courses constructed around specific learning objectives. For the new curriculum the authors developed a fourth-year course on age-related health problems in which selected issues of pediatrics, general practice, and geriatrics are integrated. The primary objective of this course is to enable students to understand the differences and similarities in approaches to health problems in different age groups. Moreover, by the end of the course students should be able to analyze the physical, psychological, and social aspects of age-specific medical problems and understand their consequences for prevention and treatment. The course covers age-specific health concerns (e.g., neonatal jaundice, growth problems, sudden infant death syndrome, anorexia nervosa, dementia, multiple pathology, frailty) as well as important age-related differences in pathophysiology, etiology, diagnosis, and treatment (e.g., acute abdomen, constipation, maltreatment, urinary incontinence, pharmacokinetics). Based on assessments and evaluations after the first three implementations, the authors conclude that the enthusiastically received course is an effective introduction to age-specific health problems.

Cellular basis for age-related differences in cardiac excitation–contraction coupling

Clinical experience indicates that infants and young children respond to a variety of cardiovascular pharmacological and physiological interventions differently than adults. What is less clear, however, are the cellular and molecular mechanisms that contribute to these age-related differences. Based largely upon results from animal models, it is apparent that developmental changes occur in numerous pathways and proteins involved in the regulation of contractile function and in the determinants of inotropic responsiveness. The purposes of this review are to provide a brief overview of cardiac excitation–contraction and to illustrate some of the important age-related differences in the mechanisms involved in calcium regulation in the heart. This scientific foundation may help to explain certain clinical observations in the very young. Furthermore, it is hoped that a better understanding of the fundamental processes involved in controlling cardiac contractile function will stimulate additional research in the search for more specific, rational and age-appropriate cardiovascular therapeutics.

A unique hormonal and behavioral hyporesponsivity to both forced novelty and d-amphetamine in periadolescent mice

The identification of critical ontogenetic periods of increased vulnerability to the effects of drugs of abuse could have a great psychobiological and clinical-therapeutical importance. Potential age-related differences in the response of the hypothalamic-pituitary-adrenal (HPA) axis to both stress and psychostimulants has been tested here in an animal model of adolescence. Periadolescent (PND 33–43) and Adult (PND>60) mice of both sexes were injected with d-amphetamine (AMPH, 0, 2, or 10 mg/kg i.p.) and immediately faced with a mild psychological stress experience, i.e. placement in a novel environment. A detailed time-course analysis of both hormonal and behavioral profiles was performed, with animals being sacrificed for trunk-blood collection at different time-points during the test (before the injection, NT group; 15, 30, or 120 min after the injection). Basal corticosterone (CORT) levels (NT group) were consistently higher in periadolescents than in adults. As a whole, a marked increment of blood CORT levels was found in mice of both ages exposed to forced novelty. However, important age-related differences were also observed, with Saline-injected periadolescents still exhibiting elevated levels of locomotion at the end of the 120-min test session and failing to show the increasing profile of CORT release over the baseline that was typical of adults. Upon an AMPH 2 administration, periadolescents exhibited a much lower profile of locomotor hyperactivity than adults, and also failed to show an increase across the course of the session in CORT release, that was observed in adults. When treated with the high AMPH 10 dose, a marked locomotor hyperactivity was found in periadolescents, which however showed much lower levels of the stereotyped licking and gnawing behavior, that was typical of adults. The present results suggest a unique profile of integrated behavioral and physiological hyporesponsivity in mice during periadolescence. The latter also represents a very useful model for the study of the issue of psychobiological risk factors involved in vulnerability to drugs of abuse in human adolescents.

Resilience, desistance and delinquent career of adolescent offenders

This study examines resilience and desistance from delinquent behaviours and attempts to identify factors which predict persistent or increased or decreased delinquency between adolescence and early childhood. A sample of 363 young people was obtained from the population of five public institutions in 1987 and 1992. Their delinquent trajectories were described on the basis of legal records. These suggested that resilience is a rare phenomenon and is associated with stable relationships, absence of diagnostic label and good adaptation to the institution. Two axes were identified which can be used to describe the population, the family background and the psychological characteristics of the individual. Information which predicted desistance from a delinquent career was identified by means of a stepwise multiple regression. Analyses were conducted separately for each age group to take account of differences in time after the placement. The results indicated that there are important age-related differences in the characteristics which influence desistance or risk. They also show length of stay in an institution to be a predictor. Desistance from further delinquency seems to depend on the time spent in the residential environment associated with an increase of guilt, an improvement of self-image and of attachment to one or more other people.

Age-related changes in O-deethylase and aldrin epoxidase activity in mouse skin and liver microsomes.

The metabolism of three model substrates for the cytochrome P450 dependent mono-oxygenase enzyme system (P450-MMO) was studied in microsomes isolated from skin and liver of young adult and senescent C57B1/6J mice. The substrates chosen were aldrin (AE), 7-ethoxycoumarin (EOC), and 7-ethoxyresorufin (EOR). Both EOC and EOR activities were lower in senescent skin. By contrast, no-age related changes were seen in senescent liver. AE was similar in young and old, in both tissues. We suggest that some important age-related differences in cutaneous xenobiotic metabolism do occur, but that these are not mirrored by hepatic differences, and are substrate specific. Previous work from these laboratories would also suggest significant species differences.

Age and Smoking Cessation Behaviors

Background. Predictors of smoking cessation behaviors during a 3-month period were examined among smokers in three age groups: 18 to 29, 30 to 49, and 50 years or older. Methods. Using random-digit dialing, telephone interviews were completed with 1,644 smokers in the Chicago metropolitan area at baseline and at a 3-month follow-up. Multiple logistic regression was used to identify factors that predicted trying to quit smoking and quitting smoking within each age group and by stage of readiness to quit smoking. Results. There were no significant differences by age in trying to quit smoking or in quitting smoking among smokers in the contemplation or preparation stages. However, there were important age differences in the factors that predicted those behaviors. In general, different factors predicted smoking cessation behaviors in each age group at each of three stages of the smoking cessation process (contemplation, preparation, and action). Also, within each age group, different factors predicted the behavior at each stage. Conclusions. The findings suggest that smokers of all ages are equally appropriate targets for smoking cessation interventions. Moreover, there are important age-related differences among smokers over the course of their smoking careers that should be considered when planning and implementing smoking cessation interventions.

Age and Readiness to Quit Smoking

The relationship between planning to quit smoking within the next 3 months and demographic characteristics, smoking history, attitudes and beliefs about smoking cessation, and motivation was analyzed among smokers in three age groups: 18 to 29, 30 to 49, and 50 years or older. Using random-digit dialing, telephone interviews were completed with 2,353 smokers before initiating a self-help, minimal-contact intervention in the Chicago metropolitan area. Multiple logistic regression was used to identify factors that predicted planning to quit within the next 3 months. The two youngest age groups were most likely to have attitudes favorable to being ready to try to quit smoking (they were more concerned about health effects of smoking, perceived a greater reduction in the likelihood of getting lung cancer, were more determined to quit, and were more confident in their ability to quit). Among all three age groups, one-fourth or less planned to quit within the next 3 months, and desire to quit was the strongest predictor in each group. Among smokers who planned to quit someday, the oldest were most likely to plan to quit within the next 3 months. The findings show that there are important age-related differences in readiness to quit smoking that should be considered when planning and evaluating smoking cessation interventions.

Age-related differences in recovery from simulated jet lag.

Six healthy young men and eight early middle-aged men were isolated from environmental time cues for 15 days. For the first 6-7 days (one or two nights adaptation, four nights baseline), their sleep and meals were scheduled to approximate their habitual patterns. Their daily routines were then shifted 6 hours earlier by terminating the sixth or seventh sleep episode 6 hours early. The new schedules were followed for the next 8 or 9 days. Important age-related differences in adjustment to this single 6-hour schedule shift were found. For the first 4-day interval after the shift, middle-aged subjects had larger increases of waking time during the sleep period and earlier termination of sleep than young subjects. They also reported larger decreases in alertness and well-being and larger increases in sleepiness, weariness and effort required to perform daily functions. The rate of adjustment of the circadian core temperature rhythm to the new schedule did not differ between groups. These results suggest that the symptoms reported by the middle-aged subjects may be due mainly to difficulty maintaining sleep at early times of the circadian day. The compensatory response to sleep deprivation may also be less robust in middle-aged individuals traveling eastbound.

Force and Oxygen Consumption in the Immature Rabbit Heart

We speculated that there are important age-related differences in the economy of left ventricular force development in the isolated heart. To assess this, we evaluated oxygen consumption and force development in newborn (less than 1 wk old) (n = 26), juvenile (4-6 wk old) (n = 26), and adult (5-7 mo old) (n = 26) isolated, isovolumic rabbit hearts. Measurements were obtained with three different interventions, including 1) changes in heart rate, 2) inotropic stimulation with isoproterenol, and 3) changes in end-diastolic pressure. We found no significant baseline differences in the economy of force development. However, when heart rate was increased by 20%, the force/oxygen consumption ratio (economy) increased in newborn hearts by approximately 37%, whereas there was a decrease in juvenile and adult hearts of approximately 27%. In addition, with increases in end-diastolic pressure above 10 mm Hg, newborn hearts increased their force/myocardial oxygen consumption ratio to 300% of the baseline value, whereas adults increased to only 160% of baseline. Isoproterenol produced no significant age-related differences in the force/myocardial oxygen consumption ratio. We conclude that there are important age-related differences in the economy of left ventricular force development in this model, but these differences are apparent only at higher heart rates and end-diastolic pressures.

Haemodynamic responses to vasopressin in anaesthetized young and adult Brattleboro rats.

1. The cardiovascular effects of pressor doses of arginine vasopressin were examined in anaesthetized Brattleboro rats with hereditary diabetes insipidus (BDI) and normal rats of the parent Long Evans (LE) strain, either 37 or 85 days old. 2. Control mean arterial blood pressure and total peripheral resistance were similar in adult animals of the two strains but were significantly lower in the young BDI rats compared with the young LE rats. 3. The three doses of vasopressin produced greater pressor responses in the young, immature LE rats compared with the young BDI rats, whereas in the adult animals vasopressin had the greater pressor effect in the BDI rats compared with the LE rats of comparable age. 4. There was little effect of vasopressin on cardiac output after the initial decrease, particularly in the BDI rats whether immature or adult, despite more prolonged decreases in heart rate. 5. These studies indicate important age-related differences in the pressor response to vasopressin in anaesthetized rats, in addition to the clear differences in response between the animals with (LE) or without (BDI) the circulating endogenous peptide.

The effect of aging on the growth of colon cancer

Reports on the effect of patient age on the prognosis for colon cancer vary. We have tested the effect of aging using a model of murine colon adenocarcinoma in groups of mice of different ages. In experiment A, Balb/c mice of age groups 3–4 weeks, 10–12 weeks, 24–32 weeks and 40–48 weeks (13 mice/group) were injected with 5 × 10 4MC-26 cells subcutaneously in the right flank. Tumors were measured twice weekly, and the rate of occurrence of tumor, mortality rate, and growth rate were calculated. In experiment B, the same plan as experiment A was used, except mice of age groups I (14 days), II (3–4 weeks), and III (20–22 months) were used with tumor doses of 1 × 10 4 cells and 5 × 10 5 cells (9–15 mice/group). In both experiments, the rate of growth of tumor, mortality rate, and sizes of tumors obtained were the same. In experiment A, the rate of occurrence of the tumors was the same in all groups, but in experiment B the occurrence of the tumor varied. A palpable tumor appeared earliest in the weanling mice (14 days), next in old mice (20–22 months), and last in the young adult group (3–4 weeks). Tumor doubling time was longest in the young adult mice (7 days), intermediate in the old mice (6.1 days), and shortest in the weanling mice (5.5 days). Established tumors grew at similar rates (as assessed by doubling time), independent of host age. Mortality rates were similar. Subtle changes in doubling time and rate of occurrence of tumor are apparent only during the “low” dose of tumor (1 × 10 4) cells, which suggests a host-immune response that is able to cope with a relatively small burden of tumor cells. Any immune system can be overwhelmed. The use of low doses of cell inoculum allows differentiation of small, but important age-related differences of colon cancer growth.

Septal lesions, cue availability, and passive avoidance acquisition by hooded male rats of two ages

When a clearly relevant cue contingency was available, the performance of young adult hooded male septal rats did not statistically differ from that of cued or noncued control animals in the acquisition of a shock passive avoidance task. Noncued young adult septal rats did, however, display the septal deficit classically observed under these conditions. The provision of cues did not improve the performance of older septal rats in terms of number of shocks to criterion; but cued rats with septal lesions in both age groups did require fewer daily sessions to meet the acquisition criterion than their control counterparts. These results suggest important age-related attentional differences between septal and control rats.