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Gait analysis system for assessment of dynamic loading axis of the knee.

The purpose of this study was (1) to demonstrate a computer-assisted gait analysis system that can visualize the locus of the dynamic loading axis on the proximal tibia joint surface, and (2) to assess the accuracy of this system in a patient with bilateral knee osteoarthritis (OA). This system uses force plate data, CT skeletal structure data and motion capture data obtained from an infrared position sensor. The relative positions between bones and markers were used to calculate skeletal model movement based on movement of the markers. The locus of the dynamic loading axis on the knee joint was defined as the point on the proximal tibia joint surface that intersected with the loading axis of the lower limb, which passed through the centre of the femoral head and the centroid of multiple points surrounded by the distal tibia joint surface contour. To assess the accuracy of this system, open MRI was used to evaluate positions of skin markers against bones in six healthy volunteers. The locus in a patient was affected by differences between the varus knee with medial compartment OA on the non-operative side and the knee treated with high tibial osteotomy (HTO) on the opposite side. At knee flexion angles of 0 degrees, 15 degrees and 30 degrees, the mean value of measurement error for point locations on the locus was within 5.6% of joint width in the lateral direction (JWLD) on the proximal tibia joint. This system can provide clinically useful information for evaluation of the dynamic loading axis on the knee joint surface.

Aged↗

Resection of the celiac axis for invasive pancreatic cancer.

Pancreatic cancer arising in the neck or body of the gland frequently presents at a more advanced stage compared with tumors arising in the pancreatic head. Vascular invasion into the celiac axis is a common contraindication to surgical resection. We report an en bloc pancreatectomy, splenectomy, and total gastrectomy with resection of the celiac axis for a pancreatic body adenocarcinoma invading the celiac axis and posterior stomach. Collateral blood flow to the liver via the gastroduodenal artery was initially identified on preoperative computed tomography (CT) imaging and confirmed intraoperatively with vascular testing before resection. One of 14 regional lymph nodes was positive for malignancy, and surgical margins were free of tumor. The patient's postoperative course was unremarkable. En bloc resection of the celiac axis and hepatic artery may be safely performed in select patients with localized pancreatic cancer invading these vessels.

Adenocarcinoma↗

Differentiating arrhythmogenic right ventricular cardiomyopathy from right ventricular outflow tract ventricular tachycardia using multilead QRS duration and axis.

BACKGROUND: Ventricular tachycardia (VT) resulting from arrhythmogenic right ventricular cardiomyopathy (ARVC) may be difficult to differentiate from idiopathic right ventricular outflow tract (RVOT) VT. OBJECTIVES: The purpose of this study was to investigate the hypothesis that QRS characteristics would be different in ARVC because of altered conduction through abnormal myocardium. METHODS: In 24 RVOT VT patients (18 women and 6 men; age 42 +/- 10 years) and 20 ARVC patients (12 women and 8 men; age 38 +/- 14 years), mean QRS duration, frontal plane axis, and precordial R-wave transition were measured in 12-lead ECGs recorded during VT. RESULTS: Mean QRS duration was longer in all 12 leads in ARVC patients. A significant difference was noted in leads I, III, aVL, aVF, V(1), V(2), and V(3) (P <.05). Leads I and aVL had the largest mean difference between ARVC and RVOT VT patients of 17.6 +/- 4.7 ms and 15.8 +/- 7.5 ms, respectively (P <.0001). Lead I QRS duration > or =120 ms had a sensitivity of 100%, specificity 46%, positive predictive value 61%, and negative predictive value 100% for ARVC. The area under the receiver operating characteristic (ROC) curve was 0.89. The addition of mean QRS axis <30 degrees (R<S in lead III) to the above criterion increased specificity for ARVC to 100%. QRS duration remained sensitive and specific in the subgroup of nine ARVC ECGs with an inferior axis (ROC area 0.82). R-wave transition was not different between groups. CONCLUSION: QRS duration is longer in ARVC compared with RVOT VT. An algorithm combining lead I QRS duration for sensitivity and axis for specificity is useful for differentiating the two tachycardia substrates.

Adult↗

Myocardial tissue Doppler and long axis function in the fetal heart.

UNLABELLED: Current echocardiographic assessment of fetal ventricular function uses relatively crude measures and this has led to inconsistencies in assessment of diastolic function. Long axis parameters may be more insightful. OBJECTIVE: To describe fetal long axis cardiac function and construct reference ranges. DESIGN: 159 normal fetuses were studied cross-sectionally using long axis M-mode to measure displacement of the atrioventricular ring and pulsed wave Doppler ultrasound to record myocardial tissue Doppler velocities at the base of the heart. RESULTS: There was a strong, almost linear gestational relationship for all but late left basal myocardial velocities. Systolic amplitude of the atrioventricular ring increased significantly. Wall thickness increased with gestation and heart rate reduced. Late diastolic mitral and tricuspid flow velocities showed no age-dependence. Right ventricular filling (p<0.0001) and myocardial lengthening (p<0.0001) and shortening velocities (p<0.0001) were higher than left. Aortic velocities were higher than pulmonary (p<0.0001). Right ventricular long axis amplitude was greater than left (p<0.0001). There were no significant differences in right (RV) and left (LV) ventricular and septal thicknesses (RV 2.5 mm [1.2-4.1]; LV (2.4 mm [1.0-4.0] and septum 2.6 mm [1.0-4.3]). Left and right myocardial tissue Doppler velocities showed similar maturation in systole (LV 0.14 vs. RV 0.10 cm/s/week) and early diastole (LV 0.16 vs. RV 0.14 cm/s/week). CONCLUSIONS: This study demonstrates maturational changes occur in both fetal systolic and diastolic ventricular function and moreover the maturational rate of myocardial tissue velocities is similar in both ventricles, despite differential loading conditions.

Blood Flow Velocity↗

Dysregulation of the Th1/Th2 cytokine profile is associated with immunosuppression induced by hypothalamic-pituitary-adrenal axis activation in mice.

Hypothalamic-pituitary-adrenal (HPA) axis activation-induced immunosuppression is associated with increased concentration of circulating corticosterone and impaired cellular immune responses. The purpose of this study was to investigate the effect of chronic HPA axis activation on the cellular immune response, Th1/Th2 cytokine profile, and concentration of corticosterone. Mice were divided into two groups: a control group comprised of healthy, untreated mice that received no stress, and an HPA axis-activated group that received stress through electric shock (ES). The delayed-type hypersensitivity reaction to dinitrofluorobenzene, splenocyte proliferative response to mitogens Concanavalin A and lipopolysaccharide, Th1 and Th2 profile, and TGF-beta1 production were measured in plasma and in culture supernatants. The corticosterone concentration was also measured in plasma. In the ES group, elevated plasma corticosterone concentration was associated with immunosuppression and a significant decrease in plasma concentrations of IL-2, IL-4, and TGF-beta1. In vitro IL-2 production in response to Con A was significantly lower in the ES group than in the control group. TGF-beta1 production in nonstimulated and stimulated cultures in response to either mitogen was significantly lower in the ES group than in the control group. Plasma concentrations of IFN-gamma and IL-10 did not differ significantly between groups. The concentrations of IFN-gamma, IL-4, and IL-10 in the supernatants of splenocytes stimulated with either mitogen and IL-4 production by nonstimulated cells were significantly higher in the ES group than in the control group. These results suggest that corticosterone mediates the immunosuppression induced by HPA axis activation, and induces dysregulation of the Th1/Th2 cytokine profile.

Animals↗

Different activation patterns of proinflammatory cytokines in melancholic and non-melancholic major depression are associated with HPA axis activity.

BACKGROUND: Recent studies showed an activation of the cytokine system and the HPA axis in major depression, although with inconsistent results. While the non-melancholic subtype displayed a proinflammatory cytokine pattern, the melancholic subtype showed signs of impaired cytokine production. In order to understand the potential pathogenic significance of these systems further, the interplay between the cytokine system and the HPA axis in depressive subtypes as well as potential changes of these systems during the course of disease were investigated. METHODS: N=37 initially unmedicated patients with acute major depression were sub-classified (melancholic vs. non-melancholic) and compared with N=37 matched healthy controls. Upon admission and after complete clinical remission, basal plasma ACTH and serum cortisol levels as well as cytokine productions (IL-1beta, IL-1 receptor antagonist (IL-1RA)) upon mitogen stimulation (PHA) were measured in a whole blood assay. RESULTS: ACTH and cortisol concentrations were significantly elevated on admission in the melancholic but not the non-melancholic subgroup. Non-melancholic patients produced significantly more IL-1beta and IL-1RA upon admission than controls or melancholic patients. The IL-1 RA/IL-1beta ratio was significantly lower in the non-melancholic compared to the melancholic subgroup and increased significantly upon remission. LIMITATIONS: Patient treatment was not standardized. No Dex/CRH test was performed. CONCLUSIONS: Melancholic patients demonstrated an activation of the HPA axis in acute stage with partial normalization upon remission but no signs of inflammation. Non-melancholic patients showed signs of inflammation in acute depression with normalization upon remission while the function of the HPA axis was normal.

Adrenocorticotropic Hormone↗

Short-term repeatability of electrocardiographic spatial T-wave axis and QT interval.

Although ventricular repolarization abnormalities reflect arrhythmic susceptibility, few reliable tools exist to identify their presence. We investigated the repeatability of the spatial T-wave axis and QT interval from standard 12-lead electrocardiograms in 63 asymptomatic volunteers. Certified technicians used a standardized protocol to digitally record 2 electrocardiograms per participant at each of 2 visits separated by 1 to 2 weeks. Absolute paired differences within and between visits were 0.19 degrees and 0.90 degrees for the T-wave axis and 1.08 and 1.55 milliseconds for the QT interval, respectively. The intraclass correlation coefficients for the T-wave axis and QT interval were 0.87 and 0.86, respectively. The impact of repeated measurements on the precision of the QT-interval measurements was evaluated for a hypothetical clinical trial aimed at detecting a drug-induced QT prolongation. We conclude that the spatial T-wave axis is as repeatable a measure of ventricular repolarization as the QT interval.

Electrocardiography↗

Hypothalamo-pituitary-adrenal axis activity predicts disease progression in multiple sclerosis.

Clinical studies have shown that groups of multiple sclerosis (MS) patients exhibit a chronically activated hypothalamo-pituitary-adrenal (HPA) axis. However, the association of HPA axis activity and disease progression in MS is unknown. In this longitudinal study over a 3-year follow-up period, we report that patients who exhibited stronger HPA reactivity at baseline were significantly more likely to experience progression as measured by the Expanded Disability Status Scale (EDSS) during the follow-up period. Furthermore, HPA axis activity correlated with progression ratings and cognitive impairment three years later. Tests of HPA axis activity may be useful biomarkers for disease progression in MS.

Adrenocorticotropic Hormone↗

An investigation of hypothalamic-pituitary-adrenal axis hyperactivity in anorexia nervosa: the role of CRH and AVP.

We hypothesised that hypothalamic-pituitary-adrenal (HPA) axis hyperactivity in anorexia nervosa (AN) is associated with (a) elevated arginine vasopressin (AVP) activity and (b) enhanced pituitary sensitivity to AVP, as it is in depressive illness. 16 Healthy women and 18 women with active AN participated in a combined dexamethasone (DXM)/corticotrophin releasing hormone (CRH) challenge test and an AVP challenge test. This combination of tests is designed to assess the functional contribution of AVP to HPA axis activity. 10 of the active AN group repeated participation after weight gain. The cortisol response to AVP was reduced by 138% in the active AN group, suggesting an impairment of pituitary sensitivity to AVP, which began to normalise with weight gain. The cortisol and adreno-corticotrophin (ACTH) responses to the DXM/CRH test were not significantly enhanced in the active AN group, suggesting that there was no elevated endogenous AVP activity augmenting the response to CRH in AN. Weight gain was associated with blunting of the endocrine response to the DXM/CRH test, which may have been related to rising oestrogen levels. Thus, contrary to the hypotheses, we did not find (a) evidence of upregulated AVP activity or (b) enhanced pituitary sensitivity to AVP in AN. These findings suggest that the mechanism of HPA axis hyperactivity differs in depression and AN, with greater involvement of AVP in depressive disorder and perhaps more reliance on CRH to drive the axis in AN. The powerful anorexigenic effect of CRH could contribute to the severity of weight loss associated with AN.

Adolescent↗

The role of endogenous cannabinoids in the hypothalamo-pituitary-adrenal axis regulation: in vivo and in vitro studies in CB1 receptor knockout mice.

Exogenous cannabinoids affect multiple hormonal systems including the hypothalamo-pituitary-adrenocortical (HPA) axis. These data suggest that endogenous cannabinoids are also involved in the HPA control; however, the mechanisms underlying this control are poorly understood. We assessed the role of endogenous cannabinoids in the regulation of the HPA-axis by studying CB1 receptor knockout (KO) and wild type (WT) mice. Basal and novelty stress-induced plasma levels of adrenocorticotropin (ACTH) and corticosterone were higher in CB1-KO than in WT mice. We investigated the involvement of the pituitary in the hormonal effects of CB1 gene disruption by studying the in vitro release of ACTH from anterior pituitary fragments using a perifusion system. Both the basal and corticotropin releasing hormone (CRH)-induced ACTH secretion were similar in CB1-KO and WT mice. The synthetic glucocorticoid, dexamethasone suppressed the CRH-induced ACTH secretion in both genotypes; thus, the negative feedback of ACTH secretion was not affected by CB1 gene disruption. The cannabinoid agonist, WIN 55,212-2 had no effects on basal and CRH-stimulated ACTH secretion by anterior pituitary slices. In our hands, the disruption of the CB1 gene lead to HPA axis hyperactivity, but the pituitary seems not to be involved in this effect. Our data are consistent with the assumption that endogenous cannabinoids inhibit the HPA-axis via centrally located CB1 receptors, however the understanding of the exact underlying mechanism needs further investigation.

Adrenocorticotropic Hormone↗

Differential expression of HPA axis homolog in the skin.

Human skin expresses elements of the hypothalamo-pituitary-adrenal (HPA) axis including pro-opiomelanocortin (POMC), corticotropin releasing hormone (CRH), the CRH receptor-1 (CRH-R1), key enzymes of corticosteroid synthesis and synthesizes glucocorticoids. Expression of these elements is organized in functional, cell type-specific regulatory loops, which imitate the signaling hierarchy of the HPA axis. In melanocytes and fibroblasts CRH-induced CRH-R1 stimulation upregulates POMC expression and production of ACTH through activation of cAMP dependent pathway(s). Melanocytes respond with enhanced production of cortisol and corticosterone, which is dependent on POMC activity. Fibroblasts respond to CRH and ACTH with enhanced production of corticosterone, but not cortisol, which is produced constitutively. Organ-cultured human scalp hair follicles also show a fully functional HPA axis equivalent, including cortisol synthesis and secretion and negative feedback regulation by cortisol on CRH expression. Thus, differential, CRH-driven responses of defined cutaneous cell populations reproduce key features of the central HPA axis at the tissue/single cell levels.

Animals↗

Mechanisms involved in the neural construction of a body-centered reference axis for extrapersonal directed movements. A hypothesis.

To localize objects in space, it is necessary to refer them to a set of coordinates that serve as a frame of reference. Advances in molecular aspects of evolutionary developmental biology reveal how axial coordinates are established in embryos. But we do not yet know how axes of reference are constructed by adult animals. The characteristics of epaxial musculature, spinal connectivity, and organization at the cortical level are reviewed. Although endowed with muscle spindles, epaxial muscles lack the monosynaptic but possess the tonic component of the stretch reflex. Motoneurons of epaxial muscles are devoid of recurrent inhibition and do not show crossed disynaptic inhibition. At motorsensory cortex (MSC), regions corresponding to the body axis receive somatosensory signals that always extend across the midline. Visual and vestibular input also converge in the zone corresponding to the body axis. This region is also endowed with a large number of callosal fibers that, by connecting the two halves of the body axis, may allow them to function and behave as a unity. In contrast, somatic signals from distal extremities are discrete, confined only to the contralateral MSC, and show short latency of responses. They do not receive either telereceptive or vestibular input. We propose that limb movements directed to extrapersonal space take place within a reference frame in which one of the axes is the result of integration at the MSC of telereceptive, proprio and somatosensory signals from the body. Vestibular input signals the effect of the force of gravity, providing directionality to the axis.

Animals↗

Perception of longitudinal body axis in microgravity during parabolic flight.

It has been proposed that an internal representation of body vertical has a prominent role in spatial orientation. This investigation investigated the ability of human subjects to accurately locate their longitudinal body axis (an imaginary straight body midline running from head to toes) while free-floating in microgravity. Subjects were tested in-flight, as well as on ground in normal gravity in both the upright and supine orientations to provide baseline measurements. The subjects wore a goggle device and were in total darkness. They used knobs to rotate two luminous lines until they were parallel to the subjective direction of their longitudinal body axis, in the roll (right/left) and the pitch (forward/backward) planes. Results showed that the error between the perceived and the objective direction of the longitudinal body axis was significantly larger in microgravity than in normal gravity. This error in this egocentric frame of reference is presumably due to the absence of somatosensory cues when free-floating. Mechanical pressure on the chest using an airbag reduced the error in perception of the longitudinal body axis in microgravity, thus improving spatial orientation.

Adult↗

Continuous i.c.v. infusion of brain-derived neurotrophic factor modifies hypothalamic-pituitary-adrenal axis activity, locomotor activity and body temperature rhythms in adult male rats.

Brain-derived neurotrophic factor is a neurotrophin belonging to the nerve growth factor family, which is involved in the differentiation and survival of many types of neurons. It also participates in neuroprotection and neuronal plasticity in adult rats. Our previous studies showed that a single brain-derived neurotrophic factor injection modifies hypothalamic-pituitary-adrenal axis activity in adult male rats. To investigate the effect of chronic brain-derived neurotrophic factor administration on some physiological parameters, adult rats were implanted with osmotic micro-pumps to deliver brain-derived neurotrophic factor continuously for 14 days in the lateral ventricle (12 microg/day/rat). mRNA levels were evaluated by in situ hybridization analysis, peptide contents and plasma hormone concentrations by radioimmunoassay. Animals were also equipped with telemetric transmitters to study locomotor activity and temperature rhythms modifications, since hypothalamic-pituitary-adrenal axis is known to modulate these two parameters. Decreased body weight was used as a control of brain-derived neurotrophic factor access to hypothalamic areas as already documented. In the hypothalamus the continuous brain-derived neurotrophic factor treatment increases: (i) the mRNA steady state levels of corticotropin releasing hormone and arginin-vasopressin in the paraventricular nucleus, the supraoptic nucleus, and the suprachiasmatic nucleus; (ii) the surface of corticotropin releasing hormone and arginin-vasopressin mRNA signals in these nuclei as detected by in situ hybridization, and (iii) the corticotropin releasing hormone and arginin-vasopressin contents. The plasma concentrations of adrenocorticotropic hormone and corticosterone were decreased and increased, respectively. Finally, this treatment increased daily locomotor activity and temperature, and provoked some circadian perturbations. These results obtained after chronic brain-derived neurotrophic factor administration extend data on the brain-derived neurotrophic factor involvement in the hypothalamic-pituitary-adrenal axis regulation and illustrate its effects on the locomotor and temperature rhythms. They also allow demonstrating that the regulation of the hypothalamic-pituitary-adrenal axis by brain-derived neurotrophic factor differs according to the brain-derived neurotrophic factor administration mode, i.e. acute injection or chronic administration.

Adrenocorticotropic Hormone↗

Limited brain diffusion of the glucocorticoid receptor agonist RU28362 following i.c.v. administration: implications for i.c.v. drug delivery and glucocorticoid negative feedback in the hypothalamic-pituitary-adrenal axis.

The experiments described herein present a method for tracking diffusion of the glucocorticoid receptor agonist RU28362 in brain following i.c.v. drug administration. A useful property of glucocorticoid receptor is that it is primarily cytoplasmic when unbound and rapidly translocates to the nucleus when bound by ligand. Thus, removal of endogenous glucocorticoids by adrenalectomy allows us to identify brain regions with activated glucocorticoid receptor after i.c.v. glucocorticoid receptor agonist treatment by examining the presence or absence of nuclear glucocorticoid receptor immunostaining. We have previously demonstrated that an i.p. injection of 150 microg/kg RU28362 1 h prior to restraint stress is sufficient to suppress stress-induced hypothalamic-pituitary-adrenal axis hormone secretion [Ginsberg AB, Campeau S, Day HE, Spencer RL (2003) Acute glucocorticoid pretreatment suppresses stress-induced hypothalamic-pituitary-adrenal axis hormone secretion and expression of corticotropin-releasing hormone hnRNA but does not affect c-fos mRNA or fos protein expression in the paraventricular nucleus of the hypothalamus. J Neuroendocrinol 15:1075-1083]. We report here, however, that in rats i.c.v. treatment with a high-dose of RU28362 (1 microg) 1 h prior to stressor onset does not suppress stress-induced hypothalamic-pituitary-adrenal axis activity. We then performed a series of experiments to examine the possible differences in glucocorticoid receptor activation patterns in brain and pituitary after i.c.v. or i.p. treatment with RU28362. In a dose-response study we found that 1 h after i.c.v. injection of RU28362 (0.001, 0.1 and 1.0 microg) glucocorticoid receptor nuclear immunoreactivity was only evident in brain tissue immediately adjacent to the lateral or third ventricle, including the medial but not more lateral portion of the medial parvocellular paraventricular nucleus of the hypothalamus. In contrast, i.p. injection of RU28362 produced a uniform predominantly nuclear glucocorticoid receptor immunostaining pattern throughout all brain tissue. I.c.v. injection of the endogenous glucocorticoid receptor agonist, corticosterone (1 microg) also had limited diffusion into brain tissue. Time-course studies indicated that there was not a greater extent of nuclear glucocorticoid receptor immunostaining present in brain after shorter (10 or 30 min) or longer (2 or 3 h) intervals of time after i.c.v. RU28362 injection. Importantly, time-course studies found that i.c.v. RU28362 produced significant increases in nuclear glucocorticoid receptor immunostaining in the anterior pituitary that were evident within 10 min after injection and maximal after 1 h. These studies support an extensive literature indicating that drugs have very limited ability to diffuse out of the ventricles into brain tissue after i.c.v. injection, while at the same time reaching peripheral tissue sites. In addition, these studies indicate that significant occupancy of some glucocorticoid receptor within the paraventricular nucleus of the hypothalamus and pituitary is not necessarily sufficient to suppress stress-induced hypothalamic-pituitary-adrenal axis activity.

Analysis of Variance↗

The nociceptin receptor antagonist [Nphe1,Arg14,Lys15]nociceptin/orphanin FQ-NH2 blocks the stimulatory effects of nociceptin/orphanin FQ on the HPA axis in rats.

Nociceptin/orphanin FQ (N/OFQ) is an opioid-related peptide that stimulates corticosterone release after i.c.v. administration in non-stressed rats. We employed in situ hybridization histochemistry to investigate N/OFQ-stimulated activation of the HPA axis at the hypothalamic and pituitary level. We have demonstrated that N/OFQ-induced activation of the HPA axis is mediated via the central N/OFQ peptide receptor (NOP) using the recently described selective NOP antagonist [Nphe(1),Arg(14),Lys(15)]nociceptin/orphanin FQ-NH(2) (UFP-101). We found that, at 30 min post-i.c.v. injection, N/OFQ dose-dependently increased plasma adrenocorticotrophin hormone and corticosterone compared with the vehicle-injected controls. N/OFQ (1.0 microg) significantly increased CRF mRNA but not AVP mRNA within the parvocellular hypothalamic paraventricular nucleus compared with the control group, and significantly increased pro-opiomelanocortin (POMC) mRNA in the anterior pituitary. While UFP-101 (1.0 microg) alone had no significant effect on plasma corticosterone concentration it blocked the effect of N/OFQ (1.0 microg) on plasma corticosterone levels when compared with N/OFQ administered alone. UFP-101 also blocked the N/OFQ-induced increase in CRF mRNA and POMC mRNA. These results demonstrate that centrally administered N/OFQ activates the HPA axis via up-regulation of CRF and POMC mRNA and stimulation of corticosterone release in rats. Further, we have demonstrated for the first time that the selective NOP receptor antagonist UFP-101 blocks these effects indicating that N/OFQ-induced HPA axis activation is mediated via central NOP receptors.

Adrenocorticotropic Hormone↗

Cortical/hippocampal monoamines, HPA-axis changes and aversive behavior following stress and restress in an animal model of post-traumatic stress disorder.

Post-traumatic stress disorder (PTSD) is characterized by monoaminergic and hypothalamic-pituitary-adrenal (HPA)-axis abnormalities. Understanding monoamine-HPA-axis responses following stress and restress may provide a greater understanding of the neurobiology of PTSD and of its treatment. Hippocampal and frontal cortex serotonin, noradrenaline and dopamine, plasma corticosterone and aversive behavior were studied in rats on day 1 and day 7 post acute stress (AS = sequential restraint stress, swim stress and halothane exposure), and on day 1 and day 7 post restress (RS = swim stress). After AS, there was an early increase in both avoidant behavior and corticosterone (1 h after stress), with subsequent normalisation (day 7), suggesting an adequate adaptive response to the stressor. However, restress (RS) evoked a significant early HPA-axis hyporesponsiveness (1 h after RS) and a later significant increase in avoidant behavior on day 7 post RS. Hippocampal serotonin, noradrenaline and dopamine concentrations were unchanged 1 h post AS, but were significantly raised on day 7 post AS. Restress, however, reduced serotonin and noradrenaline levels 1 h after and on day 7 post RS, respectively, while dopamine was unchanged. In the frontal cortex only dopamine levels were altered, being significantly elevated 1 h after AS, and reduced on day 7 post RS. AS and RS thus differently effect the HPA-axis, evoking regional-specific brain monoamine changes that underlie maladaptive behavior and other post stress-related sequelae.

Analysis of Variance↗

Concordance of DSM-IV Axis I and II diagnoses by personal and informant's interview.

The validity and reliability of using psychological autopsies to diagnose a psychiatric disorder is a critical issue. Therefore, interrater and test-retest reliability of the Structured Clinical Interview for DSM-IV Axis I and Personality Disorders and the usefulness of these instruments for the psychological autopsy method were investigated. Diagnoses by informant's interview were compared with diagnoses generated by a personal interview of 35 persons. Interrater reliability and test-retest reliability were assessed in 33 and 29 persons, respectively. Chi-square analysis, kappa and intraclass correlation coefficients, and Kendall's tau were used to determine agreement of diagnoses. Kappa coefficients were above 0.84 for substance-related disorders, mood disorders, and anxiety and adjustment disorders, and above 0.65 for Axis II disorders for interrater and test-retest reliability. Agreement by personal and relative's interview generated kappa coefficients above 0.79 for most Axis I and above 0.65 for most personality disorder diagnoses; Kendall's tau for dimensional individual personality disorder scores ranged from 0.22 to 0.72. Despite of a small number of psychiatric disorders in the selected population, the present results provide support for the validity of most diagnoses obtained through the best-estimate method using the Structured Clinical Interview for DSM-IV Axis I and Personality Disorders. This instrument can be recommended as a tool for the psychological autopsy procedure in post-mortem research.

Adjustment Disorders↗