Escitalopram in clinical practice: results of an open-label trial in a naturalistic setting

Results from randomized, placebo-controlled clinical trials have demonstrated that escitalopram is effective and well tolerated in the treatment of depression and anxiety disorders. Such trials typically employ stringent inclusion criteria that may limit the generalizability of findings to the broader population of patients treated in psychiatric and primary care practices. The objective of the current trial was to assess the effect of escitalopram treatment on depressed outpatients in naturalistic settings. This 8-week open-label trial enrolled 5,453 outpatients aged > or = 18 years with nonpsychotic major depressive disorder from primary care (n = 2,591), psychiatric (n = 2,289), and other specialty (n = 573) practices. Escitalopram was initiated at 10 mg/day, and dose could be increased to a maximum of 20 mg/day. Efficacy measures included the Clinical Global Impressions of Improvement (CGI-I) scale, Patient Global Evaluation (PGE) scale, Hospital Anxiety and Depression Scale, Sheehan Disability Scale, and 12-Item Short Form Health Survey. Overall, 76% of patients completed 8 weeks of treatment. The mean dose of escitalopram was 11.6 mg/day. At endpoint, response rates (defined as a score < or = 2 on the CGI-I or PGE) were 68% on the clinician-assessed CGI-I and 66% on the PGE. Improvement was not related to age or response to prior antidepressant treatment. Overall, 9% of patients discontinued due to adverse events. Escitalopram treatment was well tolerated and associated with robust response rates in a broadly representative population of depressed outpatients.     

Images of trauma: pain, recognition, and disavowal in the works of Frida Kahlo and Francis Bacon

The role of art in the encounter with trauma and destructiveness is comparatively studied in the works of Frida Kahlo and Francis Bacon as examples of a direct and a more indirect way of dealing with such experiences. A creative product may function intrapsychically as a kind of messenger between dissociated self-states and consciousness, and it may also serve as a witnessing presence in a self-supporting and self-constituting way. Artistic work may thus be used by the artist for an expressive as well as for a protective purpose, as a means of sympathetic participation in painful experience, or as a medium for a view from the outside. The act itself of finding and of making expressive forms at the time of traumatic experience is a remarkable assertion of the human capability to synthesize and to counteract fragmenting dissociative processes.     

Morphological changes of the soleus motoneuron pool in chronic midthoracic contused rats

This study investigated the morphological features of the soleus motoneuron pool in rats with chronic (4 months), midthoracic (T8) contusions of moderate severity. Motoneurons were retrogradely labeled using unconjugated cholera toxin B (CTB) subunit solution injected directly into the soleus muscle of 10 contused and 6 age- and sex-matched, normal controls. Morphometric studies compared somal area, perimeter, diameter, dendritic length, and size distribution of labeled cells in normal and postcontusion animals. In normal animals, motoneurons with a mean of 110.4 +/- 5.2 were labeled on the toxin-injected side of the cord (left). By comparison, labeled cells with a mean of 93.0 +/- 8.4 (a 16% decrease, P = 0.006) were observed in the chronic spinal-injured animals. A significantly smaller frequency of very small (area, approximately 100 microm2) and medium (area, 545-914 microm2) neurons, and a significantly higher frequency of larger (area, >914 microm2) neurons was observed in the labeled soleus motoneuron pools of injured animals compared with the normal controls. Dendritic bundles in the contused animals were composed of thicker dendrites, were arranged in more closely aggregated bundles, and were organized in a longitudinal axis (rostrocaudal axis). Changes in soleus motoneuron dendritic morphology also included significant decrease of total number of dendrites, increased staining, hypertrophy of primary dendrites, and significant decreased primary, secondary, and tertiary branching. The changes in size distribution and dendritic morphology in the postcontusion animals possibly resulted from cell loss and transformation of medium cells to larger cells and/or injury-associated failure of medium cells to transport the immunolabel.     

Patency of the ductus arteriosus in the premature infant: is it pathologic? Should it be treated?

PURPOSE OF REVIEW: The ductus arteriosus is a vessel that connects the pulmonary artery to the aorta and provides a pulmonary-to-systemic diversion during fetal life. In the vast majority of infants, the ductus arteriosus closes by 3 days of life. In some infants, especially preterm infants with lung disease, there is delayed closure of the ductus arteriosus. There has been controversy as to whether or when the ductus arteriosus should be closed by either pharmacologic or surgical methods. RECENT FINDINGS: There have been several epidemiologic studies describing an association between a patent ductus arteriosus and the development of morbidities, such as chronic lung disease. These associations have suggested to some that a causal relationship exists between patency of the ductus arteriosus and chronic lung disease and other morbidities. However, recent metaanalyses of randomized, controlled trials of the use of indomethacin for the prevention and treatment of the patent ductus arteriosus have not documented a decrease in the incidence of these morbidities after treatment, despite success in closure of the patent ductus arteriosus. SUMMARY: In preterm infants, patency of the ductus arteriosus may represent a normal physiologic adaptation to allow shunting from either systemic-to-pulmonary circulation (eg, in the first day of life) or from pulmonary-to-systemic circulation (eg, in the presence of severe lung disease). Therapies designed to close the ductus arteriosus are contraindicated in some settings and should not be considered a standard of care at any time until these therapies are proven to decrease long-term clinical morbidities in randomized, placebo-controlled trials.     

Contribution of synaptic depression to phase maintenance in a model rhythmic network

In many rhythmic neuronal networks that operate in a wide range of frequencies, the time of neuronal firing relative to the cycle period (the phase) is invariant. This invariance suggests that when frequency changes, firing time is precisely adjusted either by intrinsic or synaptic mechanisms. We study the maintenance of phase in a computational model in which an oscillator neuron (O) inhibits a follower neuron (F) by comparing the dependency of phase on cycle period in two cases: when the inhibitory synapse is depressing and when it is nondepressing. Of the numerous ways of changing the cycle period, we focus on three cases where either the duration of the active state, the inactive state, or the duty cycle of neuron O remains constant. In each case, we measure the phase at which neuron F fires with respect to the onset of firing in neuron O. With a nondepressing synapse, this phase is generally a monotonic function of cycle period except in a small parameter range in the case of the constant inactive duration. In contrast, with a depressing synapse, there is always a parameter regime in which phase is a cubic function of cycle period: it decreases at short cycle periods, increases in an intermediate range, and decreases at long cycle periods. This complex shape for the phase-period relationship arises because of the interaction between synaptic dynamics and intrinsic properties of the postsynaptic neuron. By choosing appropriate parameters, the cubic shape of the phase-period curve results in a small variation in phase for a large interval of periods. Consequently, we find that although a depressing synapse does not produce perfect phase maintenance, in most cases it is superior to a nondepressing synapse in promoting a constant phase difference.     

Effect of histamine H3 receptor blockade on venous return and splanchnic hemodynamics in experimental bacteremia

OBJECTIVE: In the heart, histamine H3 receptors may function as inhibitory presynaptic receptors that decrease adrenergic neural norepinephrine release in conditions of enhanced sympathetic tone. In a previous study, we found that H3 receptor blockade improved cardiac contractility and systemic hemodynamics in experimental bacteremia in dogs. Because histamine H3 receptors have been found in the splanchnic circulation in other animal models, it was not clear the extent to which H3 receptor blockade may have altered splanchnic hemodynamics, and variables of venous return, that in turn contributed to the overall improvement in systemic hemodynamics observed in the previous experiment. In the present study, we examined splanchnic hemodynamics in the presence of H3 receptor blockade in a canine model of Escherichia coli bacteremia. DESIGN: Bacteremia was produced by intravenous infusion of live E. coli administered throughout the experiment. Variables of venous return included mean systemic pressure, resistance to venous return, and mean right atrial pressure. Splanchnic measurements included hepatic and portal pressures and flows. Measurements were obtained before and after H3 receptor blockade with thioperamide maleate. The animals were studied while ventilated and anesthetized. RESULTS: H3 receptor blockade caused a decrease in mean right atrial pressure from 5.9 mm Hg pretreatment to 3.5 mm Hg posttreatment (p < .05), although it did not affect mean systemic pressure or resistance to venous return. There were no changes in portal or hepatic flows after H3 receptor blockade. The cardiac function curve after H3 receptor blockade was shifted upward and to the left compared with the pretreatment curve. CONCLUSIONS: The results showed that the primary effect of H3 receptor blockade in experimental bacteremia was attributable to an increase in inotropy. There was no evidence to indicate that H3 receptor activation contributed to altered splanchnic hemodynamics in this model.     

Disease progression markers during asymptomatic phase of HIV-1 infected children with unimpaired CD4+ cell values: evaluation of repeat CD4+ cell evaluation vs. other immunological parameters

The availability of a marker that could predict the course of disease progression in HIV-infected individuals would be of considerable relevance during the asymptomatic stage in order to undertake timely prophylactic measures. A prospective study was undertaken in a group of 42 children suffering from thalassemia major with HIV-1 infection to assess the status of immune parameters, such as peripheral CD4+ T lymphocyte (CD4+ cell) percentage, delayed type of hypersensitivity (DTH) response to recall antigens, detection rate and levels of p24 antigen, and levels of beta-2 microglobulin and cytokines in serum. All were assessed at an interval of 2 years during the asymptomatic period, (baseline and follow-up assessments) in relation to the development of AIDS defining illness within a follow-up period of 3 years. No difference could be observed in the mean CD4+ cell percentage at baseline between those who progressed subsequently to develop AIDS within the follow-up period (progressors) and those who did not (non-progressors). However, at the point of follow-up assessment the progressor group showed significantly lower CD4+ cell percentage compared to the non-progressor group (33 +/- 4.9 vs. 22 +/- 5.6; p < 0.05), although in the progressor group there was no correlation of the baseline and follow-up CD4+ cell percentage with the duration of the AIDS-free interval. However, in the progressor group there was a strong negative correlation between the rate of decline in CD4+ cell percentage and subsequent duration of the AIDS-free interval (r = -0.859). Analysis of additional immune parameters at baseline revealed that the progressor group, despite having CD4+ cell values comparable to non-progressors, showed impaired DTH response (number and total induration of positive responses being 2.0 +/- 1.23 and 6.2 +/- 1.4 in the former group vs. 3.2 +/- 0.76 and 12.6 +/- 3.80 in the later group; p < 0.05 for both the parameters), and elevated levels (mg/l) of serum beta-2 microglobulin (2.92 +/- 0.89 vs. 1.38 +/- 0.43; p < 0.05). The serum cytokine profile at baseline in the progressor group showed a T helper type-2 (Th2) dominant pattern, i.e. elevation of interleukin-4 (IL-4) and interleukin-10 (IL-10) levels with decreased levels of interleukin-2 (IL-2) and gamma interferon (gamma-IFN) compared to the non-progressor group that showed a T helper type-1 (Th1) dominant profile, i.e., elevation of IL-1 and gamma-IFN level with decreased levels of IL-4 and IL-10 (p < 0.05 for all four cytokines). The present study points out that rate of decline rather than single point of assessment of CD4+ cell values is a more reliable predictor for disease progression in HIV-1 infected children. In addition, parameters such as DTH response, serum levels of beta-2 microglobulin and serum cytokine profile, may provide valuable predictors of subsequent fall in CD4+ cell value.