Fluoxetine for the treatment of childhood anxiety disorders

OBJECTIVE: To assess the efficacy and tolerability of fluoxetine for the acute treatment of children and adolescents with generalized anxiety disorder, separation anxiety disorder, and/or social phobia. METHOD: Anxious youths (7-17 years old) who had significant functional impairment were randomized to fluoxetine (20 mg/day) (n = 37) or placebo (n = 37) for 12 weeks. RESULTS: Fluoxetine was effective in reducing the anxiety symptoms and improving functioning in all measures. Using intent-to-treat analysis, 61% of patients taking fluoxetine and 35% taking placebo showed much to very much improvement. Despite this improvement, a substantial group of patients remained symptomatic. Fluoxetine was well tolerated except for mild and transient headaches and gastrointestinal side effects. Youths with social phobia and generalized anxiety disorder responded better to fluoxetine than placebo, but only social phobia moderated the clinical and functional response. Severity of the anxiety at intake and positive family history for anxiety predicted poorer functioning at the end of the study. CONCLUSIONS: Fluoxetine is useful and well tolerated for the acute treatment of anxious youths. Investigations regarding the optimization of treatment to obtain full anxiety remission and the length of treatment necessary to prevent recurrences are warranted.     

Abnormalities in brain biochemistry associated with lack of dystrophin: studies of the mdx mouse.

Biochemical abnormalities have been reported in dystrophin-deficient muscle of boys with Duchenne (severe Xp21) muscular dystrophy or in the murine (mdx) model of the disease. These abnormalities include altered energy metabolism and responses to osmotic shock. In contrast, the situation in brain is less well understood and it is probable that dystrophin is playing a different role (or roles) in this organ. In this study we conclude that the elevation in choline-containing compounds reported in mdx brain is confined to cerebellum and hippocampus in older (> 6 months) mice. We report alterations in glucose metabolism in mdx brain under normal, awake conditions, and a reduced response of brain metabolism to the gamma-aminobutyric acid(A) receptor agonist muscimol. Using brain cortical slices we found no difference in the response of dystrophic tissue to hypoosmotic shock, but increased, substrate-dependent oxygen consumption rates at low oxygen partial pressures.     

Comparing effects of a low-energy diet and a high-protein low-fat diet on sexual and endothelial function, urinary tract symptoms, and inflammation in obese diabetic men

IntroductionAbdominal obesity and type 2 diabetes mellitus are associated with sexual and endothelial dysfunction, lower urinary tract symptoms (LUTS), and chronic systemic inflammation.AimTo determine the effects of diet‐induced weight loss and maintenance on sexual and endothelial function, LUTS, and inflammatory markers in obese diabetic men.Main Outcome MeasuresWeight, waist circumference (WC), International Index of Erectile Function (IIEF‐5) score, Sexual Desire Inventory (SDI) score, International Prostate Symptom Scale (IPSS) score, plasma fasting glucose and lipids, testosterone, sex hormone binding globulin (SHBG), inflammatory markers (high‐sensitivity C‐reactive protein [CRP] and interleukin‐6 [IL‐6]) and soluble E‐selectin, and brachial artery flow‐mediated dilatation (FMD) were measured at baseline, 8 weeks, and 52 weeks.MethodsOver 8 weeks, 31 abdominally obese (body mass index ≥ 30 kg/m², WC ≥ 102 cm), type 2 diabetic men (mean age 59.7 years) received either a meal replacement‐based low‐calorie diet (LCD) ～1,000 kcal/day (N = 19) or low‐fat, high‐protein, reduced‐carbohydrate (HP) diet (N = 12) prescribed to decrease intake by ～600 kcal/day. Subjects continued on, or were switched to, the HP diet for another 44 weeks.ResultsAt 8 weeks, weight and WC decreased by ～10% and ～5% with the LCD and HP diet, respectively. Both diets significantly improved plasma glucose, low‐density lipoprotein (LDL), SHBG, IIEF‐5, SDI and IPSS scores, and endothelial function (increased FMD, reduced soluble E‐selectin). Erectile function, sexual desire, and urinary symptoms improved by a similar degree with both diets. CRP and IL‐6 decreased with the HP diet. At 52 weeks, reductions in weight, WC, and CRP were maintained. IIEF‐5, SDI, and IPSS scores improved further.ConclusionsDiet‐induced weight loss induces rapid improvement of sexual, urinary, and endothelial function in obese diabetic men. A high‐protein, carbohydrate‐reduced, low‐fat diet also reduces systemic inflammation and sustains these beneficial effects to 1 year. Khoo J, Piantadosi C, Duncan R, Worthley SG, Jenkins A, Noakes M, Worthley MI, Lange K, and Wittert GA. Comparing effects of a low‐energy diet and a high‐protein low‐fat diet on sexual and endothelial function, urinary tract symptoms and inflammation in obese diabetic men. J Sex Med 2011;8:2868–2875.     

The effect of three cyclo-oxygenase inhibitors on intensity of primary dysmenorrheic pain

OBJECTIVE: To determine the effect of 3 different cyclo-oxygenase (COX) inhibitors on primary dysmenorrheic pain. METHOD: Eleven female patients self-medicated with either placebo (sugar), 25 mg of the COX-2 specific inhibitor rofecoxib, 50 mg of the nonselective COX inhibitor diclofenac potassium, or 7.5 mg of the COX-2 selective inhibitor meloxicam, over 4 menstrual cycles. Pain was assessed using the McGill Pain Questionnaire and a visual analog scale. RESULTS: The pain response index, present pain index, and visual analog scale were highly correlated as measures of intensity of pain (r=0.81 to 0.96, P<0.0001). Rofecoxib and diclofenac potassium both decreased the duration of dysmenorrheic pain compared with placebo (P<0.001) and with meloxicam (P<0.01), and were equally effective in improving pain, compared with placebo, after each capsule (P<0.001). When compared with placebo, both drugs also provided 50% or more pain relief, after each capsule (P<0.0048). Meloxicam, although superior to placebo, was not as effective as rofecoxib and diclofenac potassium in reducing pain, and when compared with placebo, was associated with providing 50% or more of pain relief only after the third and fourth capsules (P=0.016). CONCLUSIONS: Rofecoxib and diclofenac potassium, when taken in recommended doses, were equally effective in alleviating pain associated with primary dysmenorrhea.     

Tractography of the parahippocampal gyrus and material specific memory impairment in unilateral temporal lobe epilepsy

INTRODUCTION: Temporal lobe epilepsy (TLE) is associated with disrupted memory function. The structural changes underlying this memory impairment have not been demonstrated previously with tractography. METHODS: We performed a tractography analysis of diffusion magnetic resonance imaging scans in 18 patients with unilateral TLE undergoing presurgical evaluation, and in 10 healthy controls. A seed region in the anterior parahippocampal gyrus was selected from which to trace the white matter connections of the medial temporal lobe. A correlation analysis was carried out between volume and mean fractional anisotropy (FA) of the connections, and pre-operative material specific memory performance. RESULTS: There was no significant difference between the left and right sided connections in controls. In the left TLE patients, the connected regions ipsilateral to the epileptogenic region were found to be significantly reduced in volume and mean FA compared with the contralateral region, and left-sided connections in control subjects. Significant correlations were found in left TLE patients between left and right FA, and verbal and non-verbal memory respectively. CONCLUSION: Tractography demonstrated the alteration of white matter pathways that may underlie impaired memory function in TLE. A detailed knowledge of the integrity of these connections may be useful in predicting memory decline in chronic temporal lobe epilepsy.     

BOLD and perfusion changes during epileptic generalised spike wave activity

It is unclear whether neurovascular coupling is maintained during epileptic discharges. Knowing this is important to allow appropriate inferences from functional imaging studies of epileptic activity. Recent blood oxygen level-dependent (BOLD) functional MRI (fMRI) studies have demonstrated negative BOLD responses (NBR) in frontal, parietal and posterior cingulate cortices during generalised spike wave activity (GSW). We hypothesized that GSW-related NBR commonly reflect decreased cerebral blood flow (CBF). We measured BOLD and cerebral blood flow responses using simultaneous EEG with BOLD and arterial spin label (ASL) fMRI at 3 T. Four patients with epilepsy were studied; two with idiopathic generalized epilepsy (IGE) and two with secondary generalized epilepsy (SGE). We found GSW-related NBR in frontal, parietal and posterior cingulate cortices. We measured the coupling between BOLD and CBF changes during GSW and normal background EEG and found a positive correlation between the simultaneously measured BOLD and CBF throughout the imaged volume. Frontal and thalamic activation were seen in two patients with SGE, concordant with the electro-clinical features of their epilepsy. There was striking reproducibility of the GSW-associated BOLD response in subjects previously studied at 1.5 T. Our results show a preserved relationship between BOLD and CBF changes during rest and GSW activity consistent with normal neurovascular coupling in patients with generalized epilepsy and in particular during GSW activity. Cortical activations appear to reflect areas of discharge generation whilst deactivations reflect changes in conscious resting state activity.