Reduced T2* values in soleus muscle of patients with type 2 diabetes mellitus.

Tissue water transverse relaxation times (T2) are highly sensitive to fluid and lipid accumulations in skeletal muscles whereas the related T2* is sensitive to changes in tissue oxygenation in addition to factors affecting T2. Diabetes mellitus (DM) affects muscles of lower extremities progressively by impairing blood flow at the macrovascular and microvascular levels. This study is to investigate whether T2 and T2* are sensitive enough to detect abnormalities in skeletal muscles of diabetic patients in the resting state. T2 and T2* values in calf muscle of 18 patients with type 2 DM (T2DM), 22 young healthy controls (YHC), and 7 age-matched older healthy controls (OHC) were measured at 3T using multi-TE spin echo and gradient echo sequences. Regional lipid levels of the soleus muscle were also measured using the Dixon method in a subset of the subjects. Correlations between T2, T2*, lipid levels, glycated hemoglobin (HbA1c) and presence of diabetes were evaluated. We found that T2 values were significantly higher in calf muscles of T2DM subjects, as were T2* values in anterior tibialis, and gastrocnemius muscles of T2DM participants. However, soleus T2* values of the T2DM subjects were significantly lower than those of the older, age-matched HC cohort (22.9±0.5 vs 26.7±0.4 ms, p<0.01). The soleus T2* values in the T2DM cohort were inversely correlated with the presence of diabetes (t = -3.46, p<0.001) and with an increase in HbA1c, but not with body mass index or regional lipid levels. Although multiple factors may contribute to changes in T2* values, the lowered T2* value observed in the T2DM soleus muscle is most consistent with a combination of high oxygen consumption and poor regional perfusion. This finding is consistent with results of previous perfusion studies and suggests that the soleus in individuals with T2DM is likely under tissue oxygenation stress.

Altitude, gun ownership, rural areas, and suicide.

OBJECTIVE: The authors recently observed a correlation between state altitude and suicide rate in the United States, which could be explained by higher rates of gun ownership and lower population density in the intermountain West. The present study evaluated the relationship between mean county and state altitude in the United States and total age-adjusted suicide rates, firearm-related suicide rates, and non-firearm-related suicide rates. The authors hypothesized that altitude would be significantly associated with suicide rate. METHOD: Elevation data were calculated with an approximate spatial resolution of 0.5 km, using zonal statistics on data sets compiled from the National Geospatial-Intelligence Agency and the National Aeronautics and Space Administration. Suicide and population density data were obtained through the Centers for Disease Control and Prevention (CDC) WONDER database. Gun ownership data were obtained through the CDC's Behavioral Risk Factor Surveillance System. RESULTS: A significant positive correlation was observed between age-adjusted suicide rate and county elevation (r=0.51). Firearm (r=0.41) and non-firearm suicide rates (r=0.32) were also positively correlated with mean county elevation. CONCLUSIONS: When altitude, gun ownership, and population density are considered as predictor variables for suicide rates on a state basis, altitude appears to be a significant independent risk factor. This association may be related to the effects of metabolic stress associated with mild hypoxia in individuals with mood disorders.

The possible effect of altitude on regional variation in suicide rates.

In the United States, suicide rates consistently vary among geographic regions; the western states have significantly higher suicide rates than the eastern states. The reason for this variation is unknown but may be due to regional elevation differences. States' suicide rates (1990-1994), when adjusted for potentially confounding demographic variables, are positively correlated with their peak and capital elevations. These findings indicate that decreased oxygen saturation at high altitude may exacerbate the bioenergetic dysfunction associated with affective illnesses. Should such a link exist, therapies traditionally used to treat the metabolic disturbances associated with altitude sickness may have a role in treating those at risk for suicide.

The effect of methylphenidate on Internet video game play in children with attention-deficit/hyperactivity disorder.

OBJECTIVE: A number of studies about attention-deficit/hyperactivity disorder (ADHD) and Internet video game play have examined the prefrontal cortex and dopaminergic system. Stimulants such as methylphenidate (MPH), given to treat ADHD, and video game play have been found to increase synaptic dopamine. We hypothesized that MPH treatment would reduce Internet use in subjects with co-occurring ADHD and Internet video game addictions. METHODS: Sixty-two children (52 males and 10 females), drug-naive, diagnosed with ADHD, and Internet video game players, participated in this study. At the beginning of the study and after 8 weeks of treatment with Concerta (OROS methylphenidate HCl, Seoul, Korea), participants were assessed with Young's Internet Addiction Scale, Korean version (YIAS-K), Korean DuPaul's ADHD Rating Scale, and the Visual Continuous Performance Test. Their Internet usage time was also recorded. RESULTS: After 8 weeks of treatment, the YIAS-K scores and Internet usage times were significantly reduced. The changes in the YIAS-K scores between the baseline and 8-week assessments were positively correlated with the changes in total and inattention scores from the Korean DuPaul's ADHD Rating Scale, as well as omission errors from the Visual Continuous Performance Test. There was also a significant difference in the number of omission errors among non-Internet-addicted, mildly Internet addicted, and severely Internet addicted participants. DISCUSSION: We suggest that Internet video game playing might be a means of self-medication for children with ADHD. In addition, we cautiously suggest that MPH might be evaluated as a potential treatment of Internet addiction.

Decreased glutamate/glutamine levels may mediate cytidine's efficacy in treating bipolar depression: a longitudinal proton magnetic resonance spectroscopy study.

Targeting the glutamatergic system has been suggested as a promising new option for developing treatment strategies for bipolar depression. Cytidine, a pyrimidine, may exert therapeutic effects through a pathway that leads to altered neuronal-glial glutamate cycling. Pyrimidines are also known to exert beneficial effects on cerebral phospholipid metabolism, catecholamine synthesis, and mitochondrial function, which have each been linked to the pathophysiology of bipolar depression. This study was aimed at determining cytidine's efficacy in bipolar depression and at assessing the longitudinal effects of cytidine on cerebral glutamate/glutamine levels. Thirty-five patients with bipolar depression were randomly assigned to receive the mood-stabilizing drug valproate plus either cytidine or placebo for 12 weeks. Midfrontal cerebral glutamate/glutamine levels were measured using proton magnetic resonance spectroscopy before and after 2, 4, and 12 weeks of oral cytidine administration. Cytidine supplementation was associated with an earlier improvement in depressive symptoms (weeks 1-4; p=0.02, 0.001, 0.002, and 0.004, respectively) and also produced a greater reduction in cerebral glutamate/glutamine levels in patients with bipolar depression (weeks 2, 4, and 12; p=0.004, 0.004, and 0.02, respectively). Cytidine-related glutamate/glutamine decrements correlated with a reduction in depressive symptoms (p=0.001). In contrast, these relationships were not observed in the placebo add-on group. The study results suggest that cytidine supplementation of valproate is associated with an earlier treatment response in bipolar depression. Furthermore, cytidine's efficacy in bipolar depression may be mediated by decreased levels of cerebral glutamate and/or glutamine, consistent with alterations in excitatory neurotransmission.

Triacetyluridine (TAU) decreases depressive symptoms and increases brain pH in bipolar patients.

Eleven patients with bipolar depression were given doses of up to 18 g per day of triacetyluridine (TAU) over 6 weeks to test the effect of uridine on symptoms of depression via Montgomery-Asberg Depression Rating Scale (MADRS; Asberg, Montgomery, Perris, Schalling, & Sedvall, 1978) scores and on cellular bioenergetics using phosphorus magnetic resonance spectroscopic imaging (31P-MRSI). All patients and comparison participants (n = 9) completed baseline 31P-MRSI scans, and 9 patients completed posttherapy scans. The percentage changes for MADRS scores (Week 2, -23.8; Week 3, -34.9; Week 4, -42.5) and the time effects of TAU on MADRS scores (Week 2, z = -2.07, p = .039; Week 3, z = -4.28, p < .001; Week 4, z = -4.54, p < .001) may reflect TAU effects on early symptom improvement. TAU responders (patients who had a 50% or greater reduction in MADRS scores from baseline at any time) demonstrated a significant difference from nonresponders in pH changes from baseline (effect size = 150). These results suggest that TAU treatment may decrease symptoms of depression and improve mitochondrial functioning.

Magnetic resonance imaging findings in Hunter syndrome.

UNLABELLED: Hunter syndrome is a rare genetic lysosomal storage disease that is caused by a deficiency, or absence, of iduronate-2-sulphatase, an enzyme needed to break down specific glycosaminoglycans (GAGs). As a result, GAGs build up in various tissues throughout the body leading to adverse neurological and non-neurological effects. This literature review focuses on the neurological findings. Although few magnetic resonance imaging studies have been conducted, those done have shown that patients with Hunter syndrome generally exhibit brain atrophy, enlarged periventricular spaces and ventriculomegaly. Similar findings have been reported in other mucopolysaccharide disorders. Enzyme replacement therapy is a novel treatment which has had success in treating peripheral disease in mice and humans. CONCLUSION: Future studies should focus on how structural and chemical signatures in the brain of Hunter patients are altered before and after enzyme replacement therapy, and how those alterations correlate with clinical outcome.

MRI assessment of drug-induced fluid accumulation in humans: validation of the technology.

PURPOSE: The purpose of this study was to evaluate the feasibility of using proton and sodium magnetic resonance imaging (MRI) to detect fluid accumulation produced by fludrocortisone and nifedipine - two drugs known to cause salt/water retention by different mechanisms. MATERIALS AND METHODS: Twelve young healthy male subjects were randomly assigned to one of two groups and treated with either fludrocortisone or nifedipine for 14 or 25 days, respectively. The change in sodium MRI, as well as in proton T(2) value and T(1)-weighted signal intensity in the calf following postural change [referred to here as 'postural delta signal'(PDS)], was evaluated before, during and after drug administration. The changes in MRI PDS were compared to conventional physiological parameters, including body weight, calf volume and pitting edema. RESULTS: When compared to the baseline pretreatment values, the subjects treated with fludrocortisone showed a 5.5% increase in sodium MRI PDS (P=.01), a 2-ms increase in proton T(2) PDS of the gastrocnemius muscle (P=.06) and a body weight gain of 2.3% (P=.001) within 1 week. In the nifedipine-treated subjects, the sodium MRI PDS increased by 6% versus baseline (P=.03), while the proton T(2) PDS of the gastrocnemius muscle increased by 3.7 ms (P=.01), associated with a 0.5% weight gain (P=.55), within 3 weeks. No significant changes were noted in the T(1)-weighed images following postural change. Measurements of calf circumference, volume and pitting edema did not show consistent changes associated with the drug administration. CONCLUSION: The postural change in sodium MRI and proton T(2) signals provides a sensitive method for detecting the fluid accumulation produced by fludrocortisone and nifedipine. The MRI results are consistent with treatment-induced increases in extracellular fluid volume and correlate well with the observed weight gain. These findings support the potential utility of MRI for the evaluation of medication-induced fluid retention.