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.

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.

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.'

Assessing functional ability in persons with dementia: using family caregivers as informants.

More than one in five community-dwelling older individuals is unwilling or unable to provide information on functional abilities. In such situations the standard procedure is to augment self-reports with those of family members or other close informants. However, when these reports differ, it often is difficult to determine whether the older individual is overly optimistic about his or her functional abilities or the family informant is unduly pessimistic. This article explores factors that influence family caregiver assessments of functional abilities in older individuals with some degree of cognitive loss or impairment and presents suggestions for enhancing the accuracy and dependability of functional assessments by family informants.

Delays in thrombolytic therapy for acute myocardial infarction: association with mode of transportation to the hospital, age, sex, and race.

BACKGROUND: Although increased myocardial salvage and reduced mortality are associated with timely thrombolytic therapy for acute myocardial infarction, some patients still experience delays in treatment. OBJECTIVES: To examine treatment times in patients with acute myocardial infarction treated with thrombolytic therapy and to determine whether delays in treatment are associated with mode of transportation to the hospital, age, sex, or race. METHODS: Medical records of 176 patients with acute myocardial infarction treated with thrombolytic therapy at a community hospital were reviewed and analyzed retrospectively. RESULTS: Median times for the interval between arrival at the hospital and acquisition of a diagnostic electrocardiogram (door-to-electrocardiography time) and the interval between arrival and start of thrombolytic therapy (door-to-drug time) were 6 minutes and 34 minutes, respectively. However, 76.1% of the patients met the recommendation of the American College of Cardiology/American Heart Association of door-to-electrocardiography time of 10 minutes, and 47.2% met the recommendation of door-to-drug time of 30 minutes or less. Door-to-drug times did not differ significantly according to race or mode of transportation to the hospital. Door-to-electrocardiography and electrocardiography-to-drug times were significantly longer for older patients than for younger patients (P = .005 and P < .001, respectively), and electrocardiography-to-drug times were significantly longer for females than for males (P = .01). CONCLUSIONS: With increased emphasis on recognition and rapid treatment of patients with acute myocardial infarction at highest risk for delays in treatment, that is, women and the elderly, benefits of thrombolytic therapy might be maximized.

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.

Nefazodone treatment for chronic posttraumatic stress disorder: an open trial.

Currently, there is no standard treatment for posttraumatic stress disorder (PTSD) because of a deficit of systematic treatment trials. The symptom overlap with other mood and anxiety disorders that respond to antidepressants and the results of a limited number of antidepressant trials indicate promise for psychopharmacologic treatment. Several open trials and one controlled trial with selective serotonin reuptake inhibitors have reported improvement in the symptomatology of PTSD. In this study, a relatively new serotonergic antidepressant, nefazodone, was tested as a treatment for PTSD. Veterans with chronic PTSD (N = 36) were enrolled in an 8-week open-label trial of nefazodone. The primary outcome measure was the Clinician-Administered PTSD Scale (CAPS). Thirty-one patients completed at least 4 weeks of treatment, which was considered to be an adequate trial, and 26 patients completed the 8-week study. During treatment, there was a significant decrease in the total CAPS score and in each of three CAPS subscale scores, with most of the improvement occurring during the first 4 weeks. Comparable improvements were also seen on the Hamilton Rating Scales for Anxiety and for Depression. Nefazodone treatment was well tolerated by this patient population, with only four patients discontinuing because of adverse effects. In summary, nefazodone treatment improved the symptoms of PTSD, including the core symptoms. Placebo-controlled studies should be undertaken to further elucidate the efficacy of nefazodone in the treatment of PTSD.

Comprehensive review of the psychiatric uses of valproate.

The therapeutic effects of valproate in psychiatric conditions are most substantially recognized in bipolar disorder. However, this well-tolerated medication may be beneficial in the treatment of other mental illnesses. In this article, the authors comprehensively review studies of valproate as treatment for psychiatric conditions, including bipolar, depressive, anxiety, and psychotic disorders; alcohol withdrawal and dependence; tardive dyskinesia; agitation associated with dementia; and borderline personality disorder. Valproate shows the most promising efficacy in treating mood and anxiety disorders, with possible efficacy in the treatment of agitation and impulsive aggression, and less convincing therapeutic response in treating psychosis and alcohol withdrawal or dependence. The authors conclude with a brief summary of its mechanism of action and therapeutic spectrum.

Evidence for the segregation of a major gene for human plasma GABA levels.

Gamma-aminobutryic acid (GABA) is a major neurotransmitter in the central nervous system, and plasma levels of GABA may reflect brain GABA activity. In 35-40% of patients with mood disorders, plasma GABA levels are low compared to psychiatrically normal controls. Low plasma GABA in this subgroup of patients has characteristics of a biological trait marker for mood disorders. Low plasma GABA is also found in a subset of patients with alcohol dependence, but not in schizophrenia, anxiety, or eating disorders, suggesting some diagnostic specificity. Previous data from a small study of monozygotic twins are consistent with the hypothesis that plasma GABA levels are under genetic control. To better understand these mechanisms, we conducted a segregation analysis of plasma GABA levels in a sample of 157 individuals from 50 nuclear families. Analysis using the Class D regressive model indicated that the familial transmission of plasma GABA levels is compatible with the segregation of a recessive major gene. Our results suggest that plasma GABA levels are under single gene control. Future research should address the precise mechanisms which may account for the abnormality in GABA levels seen in a subset of patients with mood disorders.

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.

Planning cognitive-behavioral management programs for long-term care.

Recent changes in the nature and scope of nursing home practices challenge long-term care nurses to develop treatment programs that are both successful in enhancing residents' remaining quantity and quality of life, as well as cost-effective in treating specific problems. The characteristics of behavioral therapies make them ideal for the open, community environment that characterizes many long-term care (LTC) settings. Under the guidelines of the Omnibus Budget Reconciliation Act of 1987, LTC facilities are expected to initiate behavioral management programs and to train staff in behavioral management practices. The purpose of this article is to discuss five key issues that should be considered in planning behavioral management programs for LTC facilities.

Spectral analysis of low-frequency, active-head vestibulo-ocular reflex responses.

Useful medical diagnostic information has been reported from low-frequency rotational testing of the horizontal vestibulo-ocular reflex (VOR) of patients with vestibular disorders. Servocontrolled rotating systems have been used as the only practical method to generate stimuli over lower VOR frequency response ranges, the decade from 0.01 to 0.1 Hz. Active head movements have been used for testing the human VOR at higher frequencies, exceeding 0.5 Hz. We examined whether active head movements could be used also to test the VORs of subjects over lower frequency ranges, extending to 0.02 Hz. We used a swept-frequency, active head movement protocol to generate a broad-band stimulus. Eye position was recorded with electro-oculography. Head velocity was recorded with a rotational sensor attached to a head band. Six individual test epochs from human subjects were concatenated to form complex, periodic waveforms of head and eye velocity, 75 seconds in duration. Broad-band cross-spectral signal processing methods were used to compute horizontal VOR system characteristics from these waveforms extending from 0.02 to 2 Hz. The low-frequency VOR data appeared to originate from amplitude modulation of high-frequency active movements, acting as carrier signals. Control experiments and processing of simulated data from a known system excluded the possibility of signal processing artifacts. Results from six healthy subjects showed low-frequency gains and phase values in ranges similar to those from published rotational chair studies of normal subjects. We conclude that it is feasible to test the human VOR over extended low-frequency ranges using active head movements because of amplitude modulation of the head and eye signals.

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.

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.

Post-traumatic stress disorder and serotonin: new directions for research and treatment.

The overlap in clinical phenomenology and morbidity between post-traumatic stress disorder (PTSD) and such conditions as major depression, anxiety disorders and aggression, in which a serotonin dysfunction is implicated, suggests a role for serotonin in the pathophysiology of PTSD. In this paper, we review current knowledge concerning the role of serotonergic mechanisms and interventions in PTSD. Since there is no clearly effective pharmacologic intervention for this disorder, the underlying neurochemical dysfunction needs to be carefully defined so that more effective treatment can be developed. Preclinical and clinical studies of the serotonergic mechanisms in the pathophysiology of PTSD and treatment trials involving serotonergic agents are limited, but indicate considerable promise. Further investigation of a serotonergic dysfunction in PTSD and of its treatment with serotonergic agents is warranted.

Measuring problem behaviors in dementia: developing a methodological agenda.

As many as 90% of persons with dementing illness demonstrate problem behaviors that range from repetitive verbalizations, agitation, and wandering to verbal and physical aggression toward self and others. Reliable and accurate measurement of these behaviors is crucial for tracking illness progression; for monitoring the effects of pharmacologic and behavioral interventions; and for continued investigation into the correlates of caregiver stress, burden, and coping. However, there is no single, universally accepted measure or methodology for operationalizing problem behaviors, and variations in definition and measurement across studies complicate drawing meaningful conclusions about these behaviors. This article is an overview of five factors that have complicated accurate and dependable measurement of problem behaviors in dementia: the shifting domain of problem behaviors, slippage across research constructs, unexplored rater bias, scoring bias, and the absence of benchmarking studies. A methodological agenda is discussed for future investigations in this rapidly growing area of gerontological research.

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.