Priapism associated with two atypical antipsychotic agents

Priapism has been associated with many antipsychotic agents, including clozapine, risperidone, and olanzapine. This prolonged, usually painful, penile erection rarely results from the alpha-adrenergic blocking action of antipsychotics. A 22-year-old African-American man developed priapism during treatment with risperidone and, on a later occasion, during treatment with ziprasidone. The problem resolved only with substitution of other drugs for these antipsychotics. Certain patients may be more vulnerable than others to this adverse effect. Clinicians must be aware of such complications and use caution when prescribing these drugs.     

Bupropion SR vs. placebo for weight loss in obese patients with depressive symptoms

OBJECTIVE: This randomized, double-blind, placebo-controlled study evaluated the efficacy and tolerability of bupropion sustained-release (bupropion SR) in reducing weight and depressive symptoms in obese adults. RESEARCH METHODS AND PROCEDURES: Obese adults (body mass index, 30 to 44 kg/m(2)) not currently meeting criteria for major depression but with depressive symptoms (Beck Depression Inventory score 10-30) received bupropion SR 300 mg/d or placebo for 26 weeks with a 500 kcal/d-deficit diet. Patients who lost <5% of baseline weight at week 12 had bupropion SR dosage or placebo increased to 400 mg/d in a blinded fashion. RESULTS: The bupropion SR group (n = 193) lost an average of 4.4 kg (4.6% of baseline weight) vs. 1.7 kg (1.8% of baseline weight) on placebo (n = 191, p < 0.001, last-observation-carried-forward analysis). More patients in the bupropion SR group than in the placebo group (40% vs. 16% of intent-to-treat sample, 50% vs. 28% of completers, respectively) lost at least 5% of baseline weight (p < 0.05 at week 4, p < 0.001 at weeks 6 to 26). The percentage of patients reporting > or =50% decrease in depressive symptoms did not differ between groups, but depressive symptoms improved more with bupropion SR than with placebo among patients with a history of major depression (p < 0.05, weeks 4 to 26). In the sample as a whole, improvement in depressive symptoms was related to weight loss of > or =5% regardless of treatment (p < 0.0001). Bupropion SR was well-tolerated. DISCUSSION: Bupropion SR in combination with a 500 kcal/d-deficit diet facilitated weight loss. Weight loss of > or =5% may improve mood in obese patients with depressive symptoms.     

Effect of acute and short-term administration of vanadyl sulphate on insulin sensitivity in healthy active humans

Vanadium compounds have been shown to have insulin-like properties in rats and non-insulin-dependent diabetic humans. The purpose of the present study was to examine whether the effects of acute and short-term administration of vanadyl sulfate (VA) on insulin sensitivity also exist in healthy active individuals. Five male and two female participants (age: 24.9 +/- 1.5 years; height: 176.1 +/- 2.9 cm; body mass: 70.1 +/- 2.9 kg) underwent 3 oral glucose tolerance tests (OGTT). The first OGTT was performed to obtain a baseline index of insulin sensitivity (ISI). On the night preceding the second OGTT, participants ingested 100 mg of VS, and the acute effects of VS on ISI were examined. For the next 6 days, participants were instructed to ingest 50 mg of VS twice daily, and a final OGTT was performed on day 7 to determine the short-term effects of VS on ISI. No differences were found in fasting plasma glucose and insulin concentrations after VS administration. Furthermore, ISI after 1 day and 7 days of VS administration was not different compared with baseline ISI (4.8 +/- 0.1 vs. 4.7 +/- 0.1 vs. 4.7 +/- 0.1, respectively). These results demonstrate that there are no acute and short-term effects of VS administration on insulin sensitivity in healthy humans.     

The influence of post-exercise macronutrient intake on energy balance and protein metabolism in active females participating in endurance training

The purpose of this investigation was to determine the influence of post-exercise macronutrient intake on weight loss, protein metabolism, and endurance exercise performance during a period of increased training volume. Ten healthy young female endurance athletes performed 4 60-min bouts of cycle ergometry at approximately 65% of VO2peak on 4 days (day 1, 3, 4, and 6) during 2 separate 1-week periods. On day 7, participants performed a ride to exhaustion at approximately 75% of VO2peak. One of the 7-day periods served as a control condition, where a placebo beverage was consumed following the exercise bouts on days 1, 3, 4, and 6 (CON). During the other 7-day protocol (POST), participants consumed a predefined formula beverage with added carbohydrate following the exercise bouts on days 1, 3, 4, and 6. Energy intake and macronutrient proportions were the same between the 2 trials; the only difference was the timing at which the macronutrients were consumed. Calculated fat oxidation was greater during exercise on day 6 during POST as compared to CON (p < .05). Glucose and insulin concentrations were significantly higher (p < .05) following exercise during POST as compared to CON. There was a trend (p = .06) for nitrogen balance to be greater on days 5 and 6 with POST as compared to CON. Time to exhaustion during exercise on day 7 was longer during POST as compared to CON (p < .05). POST resulted in a maintenance of body weight during the 7-day protocol, while there was a significant (p < .05) reduction with CON. It was concluded that post-exercise macronutrient intake following endurance exercise can attenuate reductions in body weight and improve nitrogen balance during 7 days of increased energy expenditure. Importantly, post-exercise supplementation improved time to exhaustion during a subsequent bout of endurance exercise.     

Characteristics of HIV patients who attempt suicide

OBJECTIVE: To examine the risk factors for suicidal behaviour in human immunodeficiency virus (HIV) positive patients. METHOD: HIV substance dependent positive patients who had attempted suicide were compared with HIV substance dependent positive patients who had never attempted suicide for suicide risk factors. RESULTS: Among the 149 HIV positive patients examined almost half had attempted suicide. Significantly more HIV positive patients who had attempted suicide were female. Attempters were significantly younger than non-attempters. Significantly more of the attempters had a family history of suicidal behaviour. Attempters also reported significantly more childhood trauma, scored significantly higher for neuroticism, had experienced significantly more comorbidity with depression, and more of them had received antidepressant medication. CONCLUSION: These data suggest that both distal and proximal risk factors are involved in suicidal behaviour in HIV positive substance dependent patients.     

Relationship of birth cohort and early age at onset of illness in a bipolar disorder case registry

OBJECTIVE: Utilizing data from a previously characterized registry of subjects with bipolar illness, the authors examined age at onset of the first illness episode in cohorts of subjects born from 1900 through 1939 and from 1940 through 1959. METHOD: Demographic and clinical characteristics at the first full episode of bipolar disorder of subjects in a diagnostically validated voluntary bipolar disorder registry (N=1,218) were reviewed and subjected to statistical analyses. RESULTS: The median age at onset of the first episode of bipolar illness was lower by 4.5 years in subjects born during or after 1940 (median age=19 years), compared with subjects born before 1940 (median age=23.5 years). The proportion of subjects with bipolar disorder presenting with a prepubertal onset was significantly higher in the later birth-year cohort than in the earlier birth-year cohort. More than 50% of male and female subjects in both cohorts had a depressive episode as the first episode of bipolar illness. Subjects in each cohort who had a parent with major depression, bipolar disorder, or schizophrenia experienced their first episode nearly 4 to 5 years earlier than the other subjects in the cohort. CONCLUSIONS: Prospective epidemiological studies conducted with bipolar disorder subjects are needed to either affirm or refute these data on age at illness onset. If the results are affirmed, the early recognition of prepubertal bipolar disorder will be important, so that the condition can be treated with appropriate medications and medications that could potentially worsen the illness course can be avoided. Similarly, early recognition of bipolar illness is important, especially in women, to minimize use of antidepressant monotherapy for patients with bipolar illness. Among young people presenting with major depression as the first illness episode, a parental history of major depression, bipolar disorder, or psychosis may be a useful pointer to future bipolar disorder. Early recognition and appropriate treatment of bipolar illness may prevent the development of chronicity and serious functional impairment.     

Voluntary exercise increases neurotrophin-3 and its receptor TrkC in the spinal cord

We have evaluated changes in the expression of neurotrophin-3 (NT-3) and its tyrosine kinase C (TrkC) receptor in the neuromuscular system as a result of voluntary physical activity. We assessed changes in the mRNAs and proteins for NT-3 and TrkC in the lumbar spinal cord and associated soleus muscle following 3 and 7 days of voluntary wheel running. We used quantitative Taqman RT-PCR to measure mRNA and ELISA to assess protein levels. NT-3 mRNA and protein levels increased in the spinal cord to reach statistical significance after 7 days of exercise compared to sedentary control rats. Immunohistochemical analyses localized the elevated NT-3 to the substantia gelatinosa (SG) and nucleus of the dorsal horn. TrkC mRNA levels were significantly elevated in the spinal cord after 3 and 7 days of running. In the soleus muscle, NT-3 mRNA levels and its receptor TrkC were elevated after 3 days, while NT-3 protein levels remained unaffected. The results demonstrate that voluntary exercise has a differential effect on NT-3 as well as its receptor TrkC in the neural and muscular components of the neuromuscular system, and emphasize the role of voluntary activity on the spinal cord and muscle.     

Peripheral nerve ischemia: apolipoprotein E deficiency results in impaired functional recovery and reduction of associated intraneural angiogenic response

Apolipoprotein E-knockout (apoE KO) mice have peripheral sensory nerve defects, reduced and delayed response to noxious thermal stimuli, abnormal morphology of unmyelinated fibers, and impaired blood-nerve and blood-brain barriers. In this study, we show that, compared to wild-type mice, peripheral nerves of apoE KO mice have impaired ability to respond to ischemia, as demonstrated by measurement of motor and sensory conduction velocity. In addition, mice lacking apoE exhibit a deficit of reinnervation of ischemic epidermis, evaluated by immunofluorescent staining for the pan-neuronal marker PGP 9.5. Also regional nerve blood flow, measured by laser Doppler, and intraneural angiogenesis after ischemia are significantly compromised in apoE-deficient mice. Finally, upregulation of the angiogenic cytokine vascular endothelial growth factor (VEGF), which physiologically occurs after ischemia in the peripheral nerve of wild-type mice, is severely impaired in apoE KO mice. Among the several neural defects that have already been described in mice lacking apoE, this is the first demonstration that functional recovery to ischemia is impaired in the peripheral nerves of these animals. This deficit is mirrored by the inability of upregulating VEGF and mounting an appropriate intraneural angiogenic response following injury. These findings provide new evidence of possible interdependent relationships between VEGF, angiogenesis, and nerve function and regeneration and may provide new important information on the role of apoE in the nervous system.