Stress, allostatic load and mental health in Indigenous Australians.

The aim of this narrative review was to demonstrate how the notion of allostatic load (AL) relates directly to the mental health disparities observed between Indigenous and non-Indigenous Australians. We also endeavored to synthesize the results of the limited number of studies examining stress and AL in Indigenous Australians in order to explore the potential public health benefits of the AL concept. A range of literature examining health inequalities, psychosocial determinants of mental illness and AL was explored to demonstrate the applicability of stress biology to the significant mental health burden faced by Indigenous Australians. Furthermore, all original studies indexed in MEDLINE that provided quantitative data on primary stress biomarkers in Indigenous Australians were selected for review. Evidence of hypothalamic-pituitary-adrenal axis dysregulation and increased AL is apparent even in the handful of studies examining stress biomarkers in Indigenous Australians. Urinary, salivary, hair and fingernail cortisol, hair cortisone, urinary epinephrine, heart rate variability and the cortisol awakening response are all AL parameters which have been shown to be dysregulated in Indigenous Australian cohorts. Furthermore, associations between some of these biomarkers, self-perceived discrimination, exposure to stressful life events and symptoms of psychiatric disorders in Indigenous Australians have also been demonstrated. The continued assessment of AL biomarkers and their relationship with past traumas, lifetime stressors and socio-economic factors amongst Indigenous Australians is important to addressing the mental health this population. Measurement of AL biomarkers in a culturally appropriate manner may lead to more targeted preventative measures, interventions and policies, which mitigate the effects of stress at both the individual and societal level.

The DeStress for Success Program: effects of a stress education program on cortisol levels and depressive symptomatology in adolescents making the transition to high school.

Various studies have shown that increased activity of the hypothalamic-pituitary-adrenal (HPA) axis can predict the onset of adolescent depressive symptomatology. We have previously shown that adolescents making the transition to high school present a significant increase in cortisol levels, the main product of HPA axis activation. In the present study, we evaluated whether a school-based education program developed according to the current state of knowledge on stress in psychoneuroendocrinology decreases cortisol levels and/or depressive symptoms in adolescents making the transition to high school. Participants were 504 Year 7 high school students from two private schools in the Montreal area. Adolescents of one school were exposed to the DeStress for Success Program while adolescents from the other school served as controls. Salivary cortisol levels and depressive symptomatology were measured before, immediately after as well as 3 months after exposure to the program. Measures of negative mood were obtained at baseline in order to determine whether adolescents starting high school with specific negative moods were differentially responsive to the program. The results show that only adolescents starting high school with high levels of anger responded to the intervention with a significant decrease in cortisol levels. Moreover, we found that adolescents who took part in the intervention and showed decreasing cortisol levels following the intervention (responders) were 2.45 times less at risk to suffer from clinical and subclinical depressive states three months post-intervention in comparison to adolescents who showed increasing cortisol levels following the intervention (nonresponders). This study provides the first evidence that a school-based program on stress is effective at decreasing cortisol levels and depressive symptomatology in adolescents making the transition to high school and it helps explain which adolescents are sensitive to the program and what are some of the characteristics of these individuals.

Depressive symptoms, cortisol, and cognition during human aging: the role of negative aging perceptions.

Depressive symptoms and memory impairments are associated with heightened stress hormone levels during aging. A factor that is related to memory deficits during aging is internalized negative aging stereotypes; the idea people have about the process of aging. In this study, we assessed the associations between internalized negative aging stereotypes, depressive symptoms, subjective and objective memory assessments, and cortisol concentration among older adults. Forty older adults aged between 58 and 85 years (18 females and 22 males; mean age ± SD: 71.25 ± 8.80 years) were assessed in this study. Measures of internalized negative aging stereotypes, depressive symptoms, and both subjective and objective memory performance were assessed. Salivary samples were obtained for measurement of cortisol concentration. Stepwise linear regressions were executed in our main analyses. Internalized negative aging stereotypes were associated with increased depressive symptoms and subjective memory complaints. No significant differences were observed for objective memory performance, or cortisol concentration. Internalized negative aging stereotypes are associated with increased depressive symptomatology and subjective complaints of memory; however, they do not predict increased cortisol concentration nor objective memory performance during aging. These results indicate that the mechanism underlying the association between internalized negative aging stereotypes and cognitive impairments may not be related to dysregulations of cortisol secretion among older adults.

Association of the myocilin mt.1 promoter variant with the worsening of glaucomatous disease over time.

A major variant of myocilin (MYOC) [TIGR/MYOC mt.1 (-1000 C/G)], present in the gene's promoter, is found to be associated with more rapid progression of the glaucoma disease state. Time-to-event analyses using the Cox proportional hazards model produced substantial statistical evidence that this TIGR/MYOC mt.1(+) variant accelerates worsening for both optic disc and visual field measures of disease progression. These analyses were based on evaluations of 147 patients with primary open-angle glaucoma (POAG) over 35 years of age with an average follow-up of approximately 15 years. Our analyses showed that there are independent effects of the variant on disease progression, taking into account other relevant disease-related baseline risk factors, including age, family history, initial drug treatment, initial surgical treatment, diabetes, gender, myopia, and initial disease severity. The finding that a TIGR/MYOC mt.1(+) determination provided a strong marker for glaucoma progression, above and beyond the other baseline risk factors, suggests a clinical utility in testing for this promoter genotype.

Effect of medical and social risk factors on outcome of prematurity and very low birth weight.

A cohort of 129 infants with birth weights less than or equal to 1250 gm was followed for more than 4 1/2 years (mean +/- SD: 60 +/- 10 months) to determine the independent effects of two medical risk factors--intracranial hemorrhage and severe chronic lung disease--and a parenting risk factor (abuse or neglect) on neurodevelopmental outcome. In infants without any intracranial hemorrhage or parenting risk factors, severe chronic lung disease was not related to neurologic or cognitive outcome. Infants with increasing grades of intracranial hemorrhage had increasing rates of neurologic and cognitive abnormalities. However, the factor associated with the highest incidence of later abnormality was the parenting risk factor. We conclude that infants with medical risk factors may have additional social risk factors, and that both of these influences must be considered in an examination of the long-term sequelae of neonatal complications.

Flow cytometry measurement of nuclear RNA content in uveal melanoma.

We retrospectively studied the nuclear RNA content in uveal melanomas with known, long-term follow-up. Thirty patients had spindle cell melanomas, 25 had mixed cell tumors, and 9 had epithelioid cell neoplasms. Epithelioid cell types had a higher nuclear RNA content compared to mixed or spindle cell types (p less than 0.05). Using the Cox proportional hazards model, the nuclear RNA content appeared to be an independent prognostic indicator in uveal melanomas, and an increased nuclear RNA content was associated with a worse prognosis (p = 0.001).

Prognostic value of ambulatory blood pressure measurements: further analyses.

The value of ambulatory systolic blood pressure as a predictor of the development of cardiovascular complications was investigated in a sample of 761 hypertensive patients who had undergone ambulatory blood pressure monitoring and who were followed for an average of 5.5 years. Of the 695 patients without prior cardiovascular events at entry into the study, 11% subsequently experienced an event during the follow-up period (up to 10 years) compared to 48% of the 102 patients with a prior cardiovascular event. For each patient, a 'predicted' ambulatory systolic blood pressure was calculated, using the patient's office systolic blood pressure and the equation derived from regressing ambulatory on office blood pressure for the entire sample. By subtracting the predicted from the observed ambulatory pressure, a 'residual' ambulatory systolic blood pressure was derived for each patient, as a measure of that portion of the ambulatory pressure that could not be predicted from the office pressure. We used a Cox proportional hazards model to analyse the independent effect of each of the following patient characteristics at entry on the occurrence of subsequent cardiovascular events: sex, age, ECG evidence of left ventricular hypertrophy, hypertensive retinopathy, ambulatory systolic blood pressure, office systolic blood pressure, residual ambulatory systolic blood pressure and subsequent drug therapy. In both groups, with and without a prior cardiovascular event, women, younger patients and those with lower residual ambulatory systolic blood pressure tended to have longer periods of survival without new cardiovascular events. In the group without prior cardiovascular events, a lower office systolic blood pressure and the absence of advanced ECG evidence of left ventricular hypertrophy were also independently predictive of longer event-free survival.(ABSTRACT TRUNCATED AT 250 WORDS)

Prediction of donor-specific transfusion sensitization. I. A linear logistic model.

Using linear logistic regression, six factors were identified as important predictors of risk of DST sensitization in a group of 195 patients. Factors increasing the risk were: percent panel reactive antibody (PRA), previous transplants, and pregnancy; those decreasing the risk were HLA antigens matched, third-party blood transfusions, and Imuran administration. From this analysis, the magnitude of the effect of each factor on the risk of sensitization was obtained. An equation was then obtained that can be used to compute an estimated probability of sensitization (PS) for each patient. As a test of predictive ability of the model, the PS was calculated for 66 patients in an independent patient group. These observations were arranged according to the estimated probability and then divided into intervals of risk. Overall, for each interval, a very high level of agreement was found between the predicted and actual number of sensitized patients. A total of 16.13 patients were predicted to become sensitized and 17 actually did.

Age-related changes of the normal visual field.

We prospectively studied the age-related changes of the visual fields obtained from a selected group of 25 normal patients. The OCTOPUS automated perimeter was used to test both eyes of each patient using Program 32. We calculated the mean threshold sensitivity, volume, and surface area of the visual field and measured a linear decline with age for all three characteristics. The age-related decline in threshold sensitivity and the SE of this decline increased with eccentricity from fixation. Sensitivity declined approximately twice as rapidly at 30 degrees eccentricity as it did at fixation. The general decline in sensitivity of the visual field and the increased rate of decline with eccentricity may be related to a functional or anatomic loss of photoreceptors, ganglion cells, and higher structures.

Pathogenesis of Chandler's syndrome, essential iris atrophy and the Cogan-Reese syndrome. II. Estimated age at disease onset.

The presence of a layer of abnormal material in Descemet's membrane in eight keratoplasty specimens served as a marker to determine whether Chandler's syndrome, Essential Iris Atrophy, and the Cogan-Reese syndrome are congenital or acquired conditions. In all eight cases of the ICE syndrome, a pattern of membrane deposition was observed, which typifies acquired disorders: a completely normal prenatal layer and both normal and abnormal portions of the postnatal layer. The thickness of the membrane deposited before the onset of abnormal secretion was used to estimate a time span for possible ages at which abnormal secretion began. The estimated age intervals for all diseased specimens had their lower limits in the postnatal period. Thus, these results led us to the conclusion that abnormal Descemet's membrane first appeared in postnatal life, years before clinical recognition of disease. The possibility of a viral etiology for this unilateral endotheliopathy resulting in an altered Descemet's membrane is discussed.

Development of a clinical instrument to estimate suicide risk.

This report details the development of an empirical suicide risk scale for adults hospitalized due to a depressive or suicidal state. The authors studied 2,753 such subjects prospectively regarding 101 psychosocial variables. In a 2-year follow-up, 136 (4.94%) of the subjects had committed suicide. Rigorous statistical analysis, including a validation procedure, identified 15 variables as significant predictors of suicidal outcome. These were translated into a paper-and-pencil scale that gives an estimated risk of suicide within 2 years. Such an instrument can provide a valuable supplement to clinical judgment and a quantitative expression of suicide risk.

Two-dimensional echocardiographic determination of aortic and pulmonary artery sizes from infancy to adulthood in normal subjects.

The aorta, right pulmonary artery and pulmonary trunk were measured from the 2-dimensional echocardiogram (2-D echo) of 110 normal subjects aged 1 day to 18 years. The vessel diameters were measured from the parasternal short-axis view, the suprasternal long-axis view and the suprasternal short-axis view. Measurements were made at end-systole and at end-diastole and in both an axial and lateral direction where possible. When analyzed with respect to body surface area (BSA), the echocardiographic measurements were linearly related to the square root of the BSA, and there was inequality of variance around the relation. To establish a range of normal values for each vessel dimension, a weighted regression analysis was used to produce estimates of the regression line and a set of tolerance intervals. The systolic vessel dimension was larger than the diastolic vessel dimension and the measurement of a vessel in an axial direction was larger than the measurement of the same vessel in a lateral direction. In general, when a vessel was measured in several views, the largest diameter was obtained using the view that imaged the vessel in cross section. These data on normal values for the echocardiographic measurement of the aorta and pulmonary arteries at different BSAs should be useful for identifying patients with abnormalities in arterial size and for the serial assessment of arterial size in children who have undergone surgical or medical therapy.

Choroidal melanoma growth patterns.

Thirty patients with choroidal melanoma in whom tumour thickness was found to increase on serial examination were retrospectively studied. Often when tumours started to increase in thickness, after a period of relative quiescence, the growth rate was relatively rapid. Increased tumour thickness was associated with increased tumour growth. During the phase of active tumour growth the height of the lesion tended to increase more than exponentially. Possible inadvertent biases in the selection of the patients studied prohibit wide-ranging conclusions from these data.

Immune responses to chlamydial antigens in humans.

Antibody titer, lymphocyte stimulation and leukocyte migration inhibition with chlamydial antigens were determined repeatedly over many months on human subjects. The volunteers were retrospectively placed into four groups on the basis of clinical, laboratory and epidemiologic criteria. Group A consisted of persons with proven or probable chlamydial infection, including an illness confirmed by chlamydial isolation or seroconversion, or a clinically compatible illness with positive serologic results. Group B were sexual partners or close contacts of group A individuals. Group C were laboratory workers with prolonged exposure to viable chlamydiae or their antigens. Group D included persons of comparable age as those in groups A and B, but lacking a history of symptomatic chlamydial infection or of contact with chlamydiae. Individual cases illustrated the rise of antibody and some cell mediated immunity reactions (CMI) with active chlamydial infection. By contrast, laboratory exposure resulted in elevation of CMI but not of antibody. Statistical analysis of the results in 46 volunteers tested repeatedly indicated a strong association of specific antibody with lymphocyte stimulation, but not with leukocyte migration inhibition. Regression analysis suggested that the type of exposure markedly influenced the relationship between antibody and lymphocyte stimulation. Measurement of immunotype-specific antibody titer by microimmunofluorescence (or an equally sensitive method) remains the best laboratory indicator of past chlamydial infection. Neither antibody nor CMI can, as yet, be definitely related to resistance to re-infection in humans.