Indicators of pretreatment suicidal ideation in adults with major depressive disorder.

OBJECTIVE: In order to evaluate the presence of treatment emergent suicidal ideation (SI), it becomes necessary to identify those patients with SI at the onset of treatment. The purpose of this report is to identify sociodemographic and clinical features that are associated with SI in major depressive disorder (MDD) patients prior to treatment with a selective serotonin reuptake inhibitor. METHOD: This multisite study enrolled 265 out-patients with non-psychotic MDD. Sociodemographic and clinical features of participants with and without SI were compared post hoc. RESULTS: Social phobia, bulimia nervosa, number of past depressive episodes, and race were independently associated with SI by one or more SI measure. CONCLUSION: Concurrent social phobia and bulimia nervosa may be potential risk factors for SI in patients with non-psychotic MDD. Additionally, patients with more than one past depressive episode may also be at increased risk of SI.

A retrospective review of acute myeloid leukaemia in 35 dogs diagnosed by a combination of morphologic findings, flow cytometric immunophenotyping and cytochemical staining results (2007-2015).

Acute myeloid leukaemia (AML) is an uncommon, rapidly progressive neoplasm in dogs. The aim of this retrospective study was to characterize the clinical presentation, haematologic findings, diagnostic imaging results, treatment and survival time of a contemporary cohort of dogs with AML. Diagnosis was based on >20% blasts in bone marrow or blood identified as myeloid based on morphologic findings, flow cytometric immunophenotyping and cytochemical staining. Medical records of 35 dogs diagnosed with AML from 2007 to 2015 were included. Most dogs presented with inappetence (66%) and lethargy (57%) and physical examination findings of peripheral lymphadenopathy (74%) and tachypnea (62%). Common haematologic findings were quantifiable circulating blasts (85%; median blast count 35 700/µL; range: 300-276 500/µL), anaemia (median haematocrit 34%; range: 11%-52%) and thrombocytopenia (median 57 000/µL; range: 9000-252 000/µL). Bicytopenia and pancytopenia were each found in 44% of dogs. Follow-up information was available for 34 dogs. The overall median survival time from diagnosis was 19 days (range: 1-121 days). Clinical progression in some dogs was not as rapid as previously reported. Haematologic responses to various chemotherapeutics were documented in 3 dogs, with associated survival times of 62, 103 and 121 days. Dogs treated with prednisone or a combination of chemotherapy and prednisone had improved survival compared to dogs that received symptomatic care only (P < .0001). Our results show canine AML has an overlapping clinical presentation with lymphoma. The prognosis for canine AML remains extremely guarded. Further studies are needed to optimize therapeutic regimens for dogs with AML.

The role of personality in body image dissatisfaction and disordered eating: discrepancies between men and women.

BACKGROUND: Body image and disordered eating research has focused mostly on the female experience. The present study examined gender differences in the relationship between personality, disordered eating, and body image dissatisfaction. METHODS: Participants were 238 female and 85 male undergraduates (Mage = 20.52 years, SD = 4.22) at a Canadian university. Materials included a battery of self-report questionnaires pertaining to personality, body image, and disordered eating. RESULTS: As expected, females reported more body dissatisfaction and disordered eating than males. Personality factors were found to be significantly related to the experience of body dissatisfaction in both genders. Further, several personality traits significantly contributed to the prediction of male (high Neuroticism, low Conscientiousness) and female (high Neuroticism) body dissatisfaction beyond the influence of body mass index (BMI). Interestingly, and contrary to findings with female participants, personality traits were not significantly related to disordered eating scores in men. Among women, disordered eating scores were significantly predicted by high Neuroticism and Extraversion, and low Conscientiousness. CONCLUSIONS: Although the relationship between disordered eating, body image dissatisfaction, and personality is well-documented in females, this relation may differ for males. The focus on male body image has been increasing in Western society; exploring how males view their bodies may be beneficial to researchers and clinicians alike.

D-fenfluramine challenge in posttraumatic stress disorder.

BACKGROUND: Much progress has been made in understanding the role of catecholamines in the pathophysiology of posttraumatic stress disorder (PTSD). Recent research has broadened the scope of neuroregulation of PTSD to include serotonin. METHODS: We used the serotonin-releasing agent and reuptake inhibitor, d-fenfluramine, to assess the integrity of the serotonin-mediated prolactin release in 8 men with combat-induced PTSD and 8 healthy men. RESULTS: The veterans with PTSD had a significantly lower prolactin response to d-fenfluramine as compared to healthy control subjects. The prolactin response to d-fenfluramine was inversely correlated with the patient's level of PTSD symptomatology and measures of aggression. CONCLUSIONS: This study demonstrates a central serotonin dysfunction, as reflected in a lower prolactin response to d-fenfluramine, in patients with PTSD.

Growth hormone response to the GABAB agonist baclofen in major depressive disorder.

Growth hormone (GH) response to the gamma-aminobutyric acid B receptor agonist, baclofen, was measured in 16 male patients with major depressive disorder and in 16 age-matched healthy male controls. No significant differences were found in the GH response to baclofen between the depressed patients and controls. On repeat testing, the GH response to baclofen showed significant retest reliability in both groups. There was no significant correlation between serum baclofen levels and the GH response to baclofen. Age significantly correlated with GH response, with older subjects having lower GH response to baclofen. These data do not suggest that a blunted GH response to baclofen. represents a specific neuroendocrine feature of major depression.

Serotonin dysfunction disorders: a behavioral neurochemistry perspective.

The spectrum of efficacy of the serotonin selective reuptake inhibitor (SSRI) antidepressant drugs continues to expand. In fact, no psychiatric syndrome seems to worsen with these agents, and few studies fail to demonstrate clinical improvement in some patients, regardless of any nosologic nicety, such as precise DSM diagnosis. This suggests that the biological rubric of psychopathology is dimensional rather than categorical. New research using in vivo microdialysis shows differences in neurochemistry among SSRIs, wherein fluoxetine blocks reuptake of dopamine and norepinephrine, as well as serotonin, in medial prefrontal cortex, and fluvoxamine has a relatively more selective neurochemical profile. In the animal model of learned helplessness, which is a biobehavioral model for stress-induced anxiety causing depression, the SSRIs including fluvoxamine prevent helplessness. From these and other data, a neurotransmitter balance theory of biopsychopathology is formulated. In this hypothetical construct, dopamine, norepinephrine, and GABA modulate thought, anxiety, and mood, respectively. Serotonin is a stabilizing agent, which assists in returning the mind to its homeostatic setpoint.

Facilitation of fiberoptic nasotracheal intubation in a morbidly obese patient by simultaneous use of nasal CPAP.

A morbidly obese patient was emergently nasotracheally intubated using a fiberoptic bronchoscope. Simultaneous application of 20 cm H2O nasal continuous positive airway pressure (CPAP) to the contralateral naris using a nasal pillow helped maintain ventilation of the patient during intubation and greatly facilitated visualization of anatomic landmarks and translaryngeal passage of the bronchoscope. Fiberoptic video images of this patient's hypopharynx demonstrate the pharyngeal splinting action of nasal CPAP thus applied. This is a novel approach to difficult intubation of the obese patient.

Chest wall oscillation at 1 Hz reduces spontaneous ventilation in healthy subjects during sleep.

STUDY OBJECTIVE: The objective was to determine whether external chest wall oscillation (ECWO) during sleep (1) reduced spontaneous ventilation while maintaining adequate gas exchange over several hours, (2) influenced the quality and distribution of sleep, and (3) increased the number of respiratory events. DESIGN: Prospective controlled study with counterbalanced order of intervention. SETTING: Pulmonary function sleep laboratory. PARTICIPANTS: Seven healthy volunteers. INTERVENTION: One night of ECWO at 1 Hz (I:E = I:I; oscillation mean [SEM] from - 11.1 [0.7] to 6.0 [0.7] cm H2O) and a night during which the cuirass was applied without ECWO. MEASUREMENTS AND RESULTS: ECWO resulted in a significant decrease in spontaneous minute ventilation (VE) in all stages of sleep. ECWO was associated with a reduction in the total sleep time and a reduction in rapid eye movement (REM) sleep. The number of stage changes and the sleep efficiency did not change significantly. The mean PCO2 was similar between the control and cuirass nights (44 to 46 mm Hg). There was a significant decrease in the mean PCO2 during stage 1 (41 [2] mm Hg) and stage 2 (42 [2] mm Hg) sleep during the ECWO night. The mean arterial oxygen saturation (SaO2) was maintained at 96 to 97% throughout sleep during the control, cuirass, and ECWO nights. The apnea + hypopnea index increased (p < 0.05) during ECWO mostly due to an increase in the number of hypopneas in stage 2 sleep. During ECWO, 18 of 30 respiratory events were associated with an arousal, whereas only 2 events were associated with an arousal during the control night. CONCLUSIONS: ECWO can be tolerated for several hours and will assist ventilation while maintaining normal mean PCO2 and mean SaO2 during sleep. Monitoring of the apnea + hypopnea index and the SaO2 is recommended at the time of application. Clinical trials to define the most appropriate indications for ECWO are now necessary.

Effect of prostacyclin on microvascular pressures in a patient with pulmonary veno-occlusive disease.

Continuous-infusion prostacyclin improves symptom scores and decreases mortality in patients with primary pulmonary hypertension, but use of prostacyclin in patients with pulmonary veno-occlusive disease may precipitate pulmonary edema. A patient with pulmonary veno-occlusive disease received a graduated intravenous infusion of prostacyclin and pulmonary capillary pressures were calculated during prostacyclin dose ranging. Calculated capillary pressure increased with low-dose prostacyclin (< or = 6 ng/kg/min) but decreased with higher doses. These data suggest that the post-capillary pulmonary venules in our patient had reversible vasomotor tone, but required a higher dose of prostacyclin to vasodilate than did the precapillary arterioles.

Plasma gamma-aminobutyric acid (GABA) predicts outcome in patients with alcohol dependence.

1. Previous studies have suggested that low plasma GABA levels (< or = 100 pmol/ml) may characterize a subset of patients with alcohol dependence. 2. In order to assess the clinical relevance of this biologic finding, the authors followed 49 alcohol dependent patients for up to 18 months following inpatient treatment. Treatment outcome was assessed by continuous abstinence and continued contact with research personnel. 3. Alcohol dependent patients with low plasma GABA had significantly better outcome than patients with plasma GABA in the normal control range (101-150 pmol/ml). 4. These findings suggest that plasma GABA measures may prove to be clinically useful in identifying alcohol dependent patients at risk for relapse.

Olanzapine treatment for post-traumatic stress disorder: an open-label study.

Post-traumatic stress disorder (PTSD) is a common and increasingly diagnosed mental illness. Recent pharmacotherapeutic research on treatments for this condition has focused on antidepressant drugs with serotonergic actions. However, the presence of intrusive, psychotic-like symptoms in a substantial portion of PTSD patients raises the possibility that antipsychotics with serotonergic properties might also prove useful in treating PTSD. We conducted an open-label 8-week study of olanzapine treatment in veterans with combat-induced PTSD. Primary outcome measures in this study were the Clinician Administered PTSD Scale (CAPS) and the Clinical Global Impressions Improvement scale. Secondary outcome measures included the Hamilton Rating Scales for Depression (HRSD) and Anxiety (HRSA). Forty-eight patients enrolled in the study, and 30 completed the 8-week trial. Results of intent-to-treat and completer analyses demonstrated that all outcome measures improved significantly during treatment. Secondary analyses indicate that improvement in the intrusive symptom cluster of the CAPS was independent of improvement on the HRSD and HRSA. In conclusion, the study indicates that olanzapine treatment is useful in alleviating the symptoms of combat-induced PTSD.

The influence of gender and the estrous cycle on learned helplessness in the rat.

Although the etiology of clinical depression is unknown, women are more likely to suffer from major depressive disorder than men. In addition, in some women, there is a clear association between depression and specific phases of the menstrual cycle. Surprisingly little research has examined gender differences and the influences of the estrous cycle in this and other animal behavioral models of clinical depression. Learned helplessness is a valid animal model of stress-induced behavioral depression in which prior exposure to inescapable stress produces deficits in escape testing. Learned helplessness was studied in rats using an inescapable tail shock stress followed by a shuttle box test to determine escape latencies. Animals with mean escape latencies of >or=20 s after shuttle-box testing are defined as learned helpless. Males and normal cycling female rats in the estrus and diestrus II phases were studied. Female rats in the diestrus II phase had significantly higher escape latencies and exhibited a more helpless behavior than female rats in the estrus phase. Male rat escape latencies were intermediate between the two female phases. These results suggest a role for gonadal hormones in the development of stress-induced behavioral depression or 'learned helplessness.'

Plasma levels of gamma-aminobutyric acid and panic disorder.

Low levels of gamma-aminobutyric acid (GABA) in plasma have been associated with the presence of mood disorders in patients with major depressive disorder. We examined plasma GABA in patients with panic disorder, a disorder that is often comorbid with major depression, and in a group of control subjects. Patients with panic disorder had plasma GABA levels that did not differ significantly from levels in controls subjects. These data support the specificity of low plasma GABA as a marker for mood disorders.

Growth hormone response to baclofen: a comparison of 10-mg and 20-mg doses in healthy men.

Growth hormone (GH) response and baclofen levels were measured in seven healthy adult men following a 10-mg and a 20-mg dose of oral baclofen (gamma-aminobutyric acidB agonist) to determine the preferred dose in baclofen challenge studies. Multivariate analysis of variance (ANOVA) with repeated measures revealed no differences between the doses. However, when a univariate ANOVA with repeated measures was performed for each dose, the 10-mg dose showed no significant GH response over time, whereas the 20-mg dose showed a significant GH response over time. The average delta GH (change in GH from baseline) was 7.84 ng/ml (SD = 10.17) for the 10-mg dose and 3.34 ng/ml (SD = 3.64) for the 20-mg dose. The variability in the delta GH response to the 10-mg dose was significantly greater than the response to the 20-mg dose of baclofen. This variance in GH response was not explained by the differences in serum baclofen levels. Thus, a 20-mg baclofen dose appears to be preferable to a 10 mg-dose in baclofen challenge studies.

High-frequency autorotational testing of the vestibulo-ocular reflex.

Rotational testing is useful for clinical evaluation of vestibular dysfunction affecting the vestibulo-ocular reflex (VOR). Early applications relied on visual observation of nystagmus following turning. In modern use, control theory descriptors (e.g., gain and phase) are applied to patient data for comparisons with normal values. Motorized rotational chairs are used to passively oscillate patients with sinusoidal harmonic acceleration (SHA) stimulus profiles, usually at low frequencies (0.02 to 0.2 Hz). Changes in low-frequency phase and asymmetry, relative to normal values, provide useful indications of pathology. Vestibular autorotation testing (VAT) is a new, portable testing technique that utilizes microcomputers and patients' active head movements at high frequencies (2 to 6 Hz) to test both horizontal and vertical VOR responses. A head strap contains sensors and microelectronics for monitoring both head and eye movements. Higher-frequency VOR testing offers the advantages that the VOR is most active during locomotion at these frequencies and that other ocular motor systems are functionally insensitive above about 1 Hz. Results from VAT evaluation of patients with acute-stage Ménière's disease showed high vertical VOR gains, whereas patients receiving cisplatin chemotherapy showed pronounced low horizontal VOR gains and reduced phase lags. Practical experience in 4 years' clinical testing with the VAT has shown that this test is comfortable, efficient, clinically accurate, portable, and low cost, without requiring the dedicated, installed facility characteristic of other vestibular tests.

Use of active head movements for computerized vestibular testing.

The vestibulo-ocular reflex (VOR) is seldom tested above 2 Hz, in spite of the higher-frequency components that stimulate it during natural head movements. We tested the horizontal VOR in ten normal subjects during 18 s of active, side-to-side head motion over a frequency range from 2 to 6 Hz. Audible clicks were used as a linearly increasing frequency cue. Head velocity was monitored. The two experimental conditions were head movement while fixating a stationary wall-mounted target in dim light, and head movement in darkness with an imagined stationary target. Computed gain and phase results of the two test conditions were not significantly different, due to inactivation of the smooth pursuit system above 2 Hz. We conclude that higher-frequency VOR responses can be tested in the light by a brief, low-cost test, which does not require expensive rotating machinery.

Pharmacotherapy for post-traumatic stress disorder: a comprehensive review.

Significant advances have been made in the past 5 years in defining efficacious treatments for post-traumatic stress disorder (PTSD). Currently, sertraline is the first and only FDA-approved medication for this complex and often chronic illness. Other serotonergic antidepressants, such as paroxetine, fluoxetine and nefazodone, have well-controlled or replicated open-label evidence of efficacy. Anticonvulsants are also being studied as potential alternatives to treatment. Finally, atypical antipsychotic medications have shown promise in open-label trials. Clearly, more controlled studies are needed. This is especially true in males and in combat trauma-induced PTSD, where the effects of pharmacotherapy are less robust than in females or civilian trauma-induced PTSD. Also, there are virtually no data on pharmacotherapy for acute stress reaction or for PTSD in children. Future directions for research may focus on combination treatment in the more treatment-resistant patient populations.

Phospholipase D hydrolyzes short-chain analogs of phosphatidylcholine in the absence of detergent.

Phospholipase D is an important enzyme in signal transduction in neuronal tissue. A variety of assays have been used to measure phospholipase D activity in vitro. The most typical measure of phospholipase D activity is the production of phosphatidylethanol in the presence of ethanol. Phosphatidylethanol is a product of transphosphatidylation activity that is considered a unique property of phospholipase D. To support transphosphatidylation activity, high concentrations of ethanol may be required. Furthermore, most assays in the literature utilize a detergent. These extreme conditions, detergent and ethanol, may alter phospholipase D and hinder the study of its regulation. In this manuscript we describe an assay that eliminates these potentially confounding conditions. It utilizes high specific activity [3H]butanol as a nucleophilic receptor. This eliminates the need for high concentrations of alcohol. The substrate is an analog of phosphatidylcholine that contains short-chain fatty acids, 1,2-dioctanoyl-sn-glycero-3-phosphocholine. Phospholipase D readily hydrolyzes this substrate in the absence of detergent. This novel assay should be useful in the further characterization of phospholipase D.

A survey of sexual trauma treatment provided by VA medical centers.

In 1992 Congress mandated the Department of Veterans Affairs to provide treatment to veterans traumatized by sexual assault experienced during active military duty. A 1995 survey of how VA medical centers had responded to this mandate indicated that 51 percent of 136 centers had established a sexual trauma treatment team. Teams treated a mean+/-SD of 5.5+/-10 patients a week, and newly referred veterans waited a mean of 3.3+/-4 days for evaluation. Teams varied in the discipline mix of providers, training, organizational structure, services offered, and caseload. Medical centers without dedicated treatment teams offered nonspecialized services to sexually traumatized veterans or offered community referrals for sexual trauma treatment services.