Effects of glucocorticoids on declarative memory function in major depression.

BACKGROUND: Major depression has been associated with hypercortisolemia in a subset of patients with depression. Administration of exogenous cortisol and other glucocorticoids to healthy human subjects has been observed to result in a transient impairment in verbal declarative memory function. The purpose of this study was to assess the effects of the glucocorticoid, dexamethasone, on verbal declarative memory function in patients with untreated unipolar major depressive disorder (MDD). METHODS: Fifty two men and women with (n = 28) and without (n = 24) MDD received placebo or dexamethasone (1 mg and 2 mg on 2 successive days) in a double-blind, randomized fashion. Declarative memory was assessed with paragraph recall at baseline (day 1) and day 3. RESULTS: There was a significant interaction between diagnosis and drug (dexamethasone vs. placebo) on paragraph recall. In the healthy subjects, memory improved from baseline to day 3 with placebo and was unchanged with dexamethasone, whereas in MDD patients memory function showed a pattern of decreasing with placebo and improving with dexamethasone from baseline to day 3. CONCLUSIONS: These findings are consistent with an altered sensitivity of declarative memory function in MDD to regulation by glucocorticoids. Possible explanations of the findings include alterations in glucocorticoid receptors in the hippocampus or other brain regions mediating declarative memory, or differential sensitivity to dexamethasone-induced reductions in cortisol, in patients with MDD.     

Tracking errors related to cardiac cycle: a new approach

One-dimensional manual tracking was investigated in relation to cardiac activity. The task of the subjects was, by means of a joy-stick, to maintain a spotlight between two vertical lines moving horizontally across an oscilloscope screen. Error incidence was time-locked with respect to the cardiac cycle. Error rate was higher for faster (2-s trial periods) than for slower (3-s trial periods) target movement. Using linear-ramp and sinusoidal movements, it was demonstrated that error incidence is associated with positive and negative cardiac acceleration.     

Comparison of inhomogeneity correction algorithms in small photon fields

Algorithms such as convolution superposition, Batho, and equivalent pathlength which were originally developed and validated for conventional treatments under conditions of electronic equilibrium using relatively large fields greater than 5 x 5 cm2 are routinely employed for inhomogeneity corrections. Modern day treatments using intensity modulated radiation therapy employ small beamlets characterized by the resolution of the multileaf collimator. These beamlets, in general, do not provide electronic equilibrium even in a homogeneous medium, and these effects are exaggerated in media with inhomogenieties. Monte Carlo simulations are becoming a tool of choice in understanding the dosimetry of small photon fields as they encounter low density media. In this study, depth dose data from the Monte Carlo simulations are compared to the results of the convolution superposition, Batho, and equivalent pathlength algorithms. The central axis dose within the low-density inhomogeneity as calculated by Monte Carlo simulation and convolution superposition decreases for small field sizes whereas it increases using the Batho and equivalent pathlength algorithms. The dose perturbation factor (DPF) is defined as the ratio of dose to a point within the inhomogeneity to the same point in a homogeneous phantom. The dose correction factor is defined as the ratio of dose calculated by an algorithm at a point to the Monte Carlo derived dose at the same point, respectively. DPF is noted to be significant for small fields and low density for all algorithms. Comparisons of the algorithms with Monte Carlo simulations is reflected in the DCF, which is close to 1.0 for the convolution-superposition algorithm. The Batho and equivalent pathlength algorithms differ significantly from Monte Carlo simulation for most field sizes and densities. Convolution superposition shows better agreement with Monte Carlo data versus the Batho or equivalent pathlength corrections. As the field size increases the DCF's for all algorithms converge toward 1.0. The largest differences in DCF are at the interface where changes in electron transport are greatest. For a 6 MV photon beam, electronic equilibrium is restored at field sizes above 3 cm diameter and all of the algorithms predict dose in and beyond the inhomogeneous region equally well. For accurate dosimetry of small fields within and near inhomogeneities, however, simple algorithms such as Batho and equivalent pathlength should be avoided.     

Visual perception: double pulse temporal resolution. (Lack of contingency upon the phase of resting cardiac and respiratory cycle)

Double light pulse resolution required longer inter-pulse time intervals of short duration of the pulse. The threshold of double pulse discrimination was not contingent upon the actual phase of cardiac or respiratory cycle.     

Cardiac frequency, phase and errors in one-dimensional sensorimotor tracking.

One dimensional manual tracking was investigated in relation to actual heart rate and phase of cardiac cycle. Higher heart rate was combined with increased tracking error incidence and decreased successful tracking time (light spot inside target). Error incidence was time-locked with respect to the phase of cardiac cycle.     

Reproductive Health Knowledge About Miscarriage: A Cross-Sectional Study of University Students

Maternal and Child Health Journal - To assess university students’ knowledge of reproductive health information about miscarriage. A single-centre, cross-sectional study was carried out using...     

Daily CT localization for correcting portal errors in the treatment of prostate cancer

Introduction: Improved prostate localization techniques should allow the reduction of margins around the target to facilitate dose escalation in high-risk patients while minimizing the risk of normal tissue morbidity. A daily CT simulation technique is presented to assess setup variations in portal placement and organ motion for the treatment of localized prostate cancer.

Methods and Materials: Six patients who consented to this study underwent supine position CT simulation with an alpha cradle cast, intravenous contrast, and urethrogram. Patients received 46 Gy to the initial Planning Treatment Volume (PTV₁) in a four-field conformal technique that included the prostate, seminal vesicles, and lymph nodes as the Gross Tumor Volume (GTV₁). The prostate or prostate and seminal vesicles (GTV₂) then received 56 Gy to PTV₂. All doses were delivered in 2-Gy fractions.

After 5 weeks of treatment (50 Gy), a second CT simulation was performed. The alpha cradle was secured to a specially designed rigid sliding board. The prostate was contoured and a new isocenter was generated with appropriate surface markers. Prostate-only treatment portals for the final conedown (GTV₃) were created with a 0.25-cm margin from the GTV to PTV. On each subsequent treatment day, the patient was placed in his cast on the sliding board for a repeat CT simulation. The daily isocenter was recalculated in the anterior/posterior (A/P) and lateral dimension and compared to the 50-Gy CT simulation isocenter. Couch and surface marker shifts were calculated to produce portal alignment. To maintain proper positioning, the patients were transferred to a stretcher while on the sliding board in the cast and transported to the treatment room where they were then transferred to the treatment couch. The patients were then treated to the corrected isocenter. Portal films and electronic portal images were obtained for each field.

Results: Utilizing CT–CT image registration (fusion) of the daily and 50-Gy baseline CT scans, the isocenter changes were quantified to reflect the contribution of positional (surface marker shifts) error and absolute prostate motion relative to the bony pelvis. The maximum daily A/P shift was 7.3 mm. Motion was less than 5 mm in the remaining patients and the overall mean magnitude change was 2.9 mm. The overall variability was quantified by a pooled standard deviation of 1.7 mm. The maximum lateral shifts were less than 3 mm for all patients. With careful attention to patient positioning, maximal portal placement error was reduced to 3 mm.

Conclusion: In our experience, prostate motion after 50 Gy was significantly less than previously reported. This may reflect early physiologic changes due to radiation, which restrict prostate motion. This observation is being tested in a separate study. Intrapatient and overall population variance was minimal. With daily isocenter correction of setup and organ motion errors by CT imaging, PTV margins can be significantly reduced or eliminated. We believe this will facilitate further dose escalation in high-risk patients with minimal risk of increased morbidity. This technique may also be beneficial in low-risk patients by sparing more normal surrounding tissue.     

Cerebrospinal fluid corticotropin-releasing hormone in healthy humans: effects of yohimbine and naloxone

CRH neurons projecting from the paraventricular nucleus (PVN) of the hypothalamus to the median eminence control hypothalamic-pituitary-adrenal (HPA) axis activity. However, CRH neurons outside the PVN as well as PVN neurons projecting to sites other than the median eminence also contribute to the stress response and may play a role in mood and anxiety disorders. We have attempted to investigate possible noradrenergic and opioid regulation of these non-HPA CRH neurons. We hypothesized that yohimbine (an alpha2-adrenergic antagonist) would have stimulatory action on non-HPA CRH neurons, whereas naloxone (a mu-opioid receptor antagonist) would not have this effect. Adult normal volunteers received i.v. yohimbine (n = 5; 0.4 microg/kg), naloxone (n = 4; 125 microg/kg), or placebo (n = 3; 0.9% saline). Cerebrospinal fluid (CSF) was collected continuously, and concentrations of CSF CRH, CSF norepinephrine (NE), and plasma cortisol were measured. Administration of either yohimbine or naloxone caused significant increases in plasma cortisol concentrations over time. Although yohimbine robustly increased CSF NE levels and appeared to increase CSF CRH levels, these effects were not seen after naloxone or placebo administration. Intraindividual correlations were not observed between the measured concentrations of plasma cortisol and CSF CRH for any of the subjects. The results support the idea that CSF CRH concentrations reflect the activity of non-HPA CRH neurons. Although both yohimbine and naloxone stimulated the HPA axis, only yohimbine appeared to have stimulatory effects on central NE and non-HPA CRH.     

Inherited bleeding disorders: disorders of platelet adhesion and aggregation

Platelet aggregation at sites of vascular injury is essential for the formation of the primary haemostatic plug. The mechanism of platelet aggregation under conditions of physiological flow is a complex multistep process, which requires the synergistic action of several different platelet receptors. Platelet interaction with collagen at sites of damage to the vascular endothelium involves adhesion, activation, secretion of platelet granular contents and finally aggregation. Other agonists other than collagen, such as fibrinogen, vWF and soluble agonists released from activated platelets (thromboxane A2 (TXA2) and ADP) are involved in platelet aggregation. Platelets express a variety of receptors including GP Ib-IX-V, GP VI, GP Ia-IIa and GP IIb-IIIa. One aspect of this complexity of function is the variety of inherited defects of platelet function. Hereditary disorders of platelet adhesion are Bernard-Soulier syndrome and von Willebrand disease. Glanzmann thrombasthenia is an inherited disorder of platelet aggregation. The application of molecular biology to the study of platelet disorders has identified defects in other collagen receptors, ADP receptors and TXA2 receptors. Defects affecting TXA2 production, the generation of procoagulant activity and secretion from dense bodies and alpha-granules are also encountered. Other rare diseases, Chediak-Higashi, Hermansky-Pudlak and Wiskott-Aldrich syndrome also affect platelet storage granules. In this article, recent advances in the understanding of platelet function and knowledge of inherited disorders that affect platelet adhesion and aggregation is reviewed. As progress advances towards individualisation of therapy the phenotypic bleeding tendency of each patient becomes relevant.