Cerebrovascular and metabolic perturbations in delayed heavy charged particle radiation injury

Focal heavy charged particle irradiation of the rabbit brain created defined lesions which were observable by nuclear magnetic resonance (NMR) and positron emission tomography (PET) imaging techniques. The lesions appeared approximately 9-11 months after left partial hemibrain irradiation with 30 Gy (230 MeV/u helium ions), and were restricted to the white matter tracts and deep perithalamic and thalamic regions. 82Rubidium PET and Gadolinium DTPA enhanced NMR imaging were used to detect blood-brain barrier perturbations. 18Fluordeoxyglucose PET studies demonstrated widespread decreases in cerebral glucose uptake in the cortex and thalamus of the irradiated hemisphere. NMR and PET imaging results correlated well with histological findings. Rabbits irradiated with 15 Gy did not demonstrate any abnormalities in the brain with sequential NMR scans through 14 months post-irradiation.     

Striatal D(2) receptor occupancy in bipolar patients treated with olanzapine.

We explored the relationship between striatal dopamine-2 (D(2)) receptor occupancy and extra-pyramidal symptoms (EPS) in bipolar patients receiving olanzapine. Seventeen patients with a DSM-IV diagnosis of bipolar disorder were treated with 5-45 mg/day olanzapine for at least 14 days. After that period, D(2) receptor occupancy was determined using Iodobenzamide (IBZM) and SPECT. EPS were assessed by the Simpson-Angus Scale (SAS) and Barnes-Akathisia Scale (BAS). We found a dose-dependent increase in occupancy: 5 mg led to 28-50%, 10 mg to 40-68%, 15 mg to 69%, 20 mg to 57-66%, 30 mg to 66% and 45 mg to 80% D(2) receptor occupancy; and a significant correlation between plasma levels and occupancy (R(2)=.55, P=.001). Similar to schizophrenic patients, bipolar patients did not exhibit EPS at D(2) occupancy levels of 28 to 80%. Although we did not find an increased vulnerability for acute EPS in bipolar patients receiving olanzapine at clinical relevant doses, this needs to be replicated with larger sample sizes.     

Successful treatment of OCD with a micronutrient formula following partial response to Cognitive Behavioral Therapy (CBT): A case study

Obsessive Compulsive Disorder (OCD) affects 0.5–2% of young people many of whom are resistant to conventional treatments. This case study describes an 18-year-old male with OCD who first underwent cognitive behavioral therapy (CBT) for a 1-year period with a modest response (his OCD had shifted from severe to moderate). Within a year, his anxiety had deteriorated back to the severe range and he now had major depression. He then entered an ABAB design trial using a nutritional formula consisting mainly of minerals and vitamins (together, known as micronutrients). After 8 weeks on the formula, his mood was stabilized, his anxiety reduced, and his obsessions were in remission. The treatment was then discontinued for 8 weeks, during which time his obsessions and anxiety worsened and his mood dropped. Reintroduction of the formula again improved the symptoms. This case illustrates the importance of considering the effect micronutrients have on mental illness.     

Reduced serotonin-1A receptor binding in social anxiety disorder.

BACKGROUND: Results from studies in serotonin-1A (5-HT1A) knockout mice and previous positron emission tomography (PET) studies in humans imply a role for 5-HT1A receptors in normal state anxiety as well as in certain anxiety disorders. The objective of this study was to investigate 5-HT1A receptor binding potential (BP) in social anxiety disorder (SAD). METHODS: Using PET and [carbonyl-11C]WAY-100635, we compared a homogeneous group of 12 unmedicated, male SAD patients with 18 healthy control subjects (HC). A multivariate ANOVA with all regional BP values as dependent variables, age and four radiochemical variables as covariates was performed. RESULTS: We found a significantly lower 5-HT1A BP in several limbic and paralimbic areas but not in the hippocampus (p = .234) of SAD patients. The difference in 5-HT1A binding was most significant in the amygdala (-21.4%; p = .003). There was also a more than 20% lower 5-HT(1A) BP of SAD patients in the anterior cingulate cortex (p = .004), insula (p = .003), and dorsal raphe nuclei (p = .030). CONCLUSIONS: The lower 5-HT1A binding in the amygdala and mesiofrontal areas of SAD patients is consistent with 1) preclinical findings of elevated anxiety in 5-HT1A knockout mice, 2) a previous PET study in healthy volunteers showing an inverse correlation between 5-HT1A BP and state anxiety, and 3) another human PET study in patients with panic disorder showing reduced 5-HT1A binding, thus corroborating the potential validity of 5-HT1A receptors as targets in the treatment of human anxiety disorders.     

Balanced analgesia after hysterectomy: the effect on outcomes.

Balanced analgesia (an opioid and a nonsteroidal anti-inflammatory agent) after hysterectomy often leads to better postoperative pain outcomes. Researchers compared post-hysterectomy patients who received balanced analgesia with those who received only morphine patient-controlled analgesia, and their relationship with pain scores, ambulation, and hospital length of stay.     

Role of five platelet membrane glycoprotein polymorphisms in branch retinal vein occlusion.

To determine whether polymorphisms of platelet surface glycoprotein associated with arterial thrombosis are risk factors for branch retinal vein occlusion. A case-control study in which 69 patients with branch retinal vein occlusion and 147 controls who attended the eye clinic for nonvascular complications participated. DNA was extracted from whole blood and analyzed for genotyping of platelet glycoprotein polymorphisms by polymerase chain reactions and specific restricted enzymes. No relationship was found between the four platelet glycoprotein polymorphisms i.e. GPIa C807T, VNTR and Kozak of glycoprotein Ibalpha, the HPA-1 of glycoprotein IIIa and the occurrence of branch retinal vein occlusion. The HPA-2 polymorphism was found in 18 out 60 (30%) patients with branch retinal vein occlusion in comparison with 27 out 142 (19%) of controls, with an estimated odds ratio of 1.8 (95% confidence interval, 0.91-3.65). The four platelet glycoprotein polymorphisms are not risk factors for branch retinal vein occlusion and therefore it seems unnecessary to screen those patients for it. A larger study is required, however, to determine whether HPA-2 is a novel risk factor for branch retinal vein occlusion.     

Selective alleviation of compulsive lever-pressing in rats by D1, but not D2, blockade: possible implications for the involvement of D1 receptors in obsessive-compulsive disorder.

Rats undergoing extinction of lever-pressing for food after the attenuation of an external feedback for this behavior exhibit excessive lever-pressing unaccompanied by an attempt to collect a reward. This behavior may be analogous to the excessive and unreasonable behavior seen in obsessive-compulsive disorder. In the present study, we tested the hypothesis that the compulsive behavior induced by signal attenuation is mediated via D(1) rather than D(2) receptors. Administration of 0.005, 0.01 and 0.03 mg/kg of the D(1) antagonist SCH 23390 reduced the number of compulsive lever-presses without affecting the number of lever-presses followed by an attempt to collect a reward. In contrast, administration of 0.005, 0.01, 0.024, 0.036 and 0.05 of the D(2) antagonist haloperidol dose-dependently decreased both types of lever-presses. In addition, haloperidol at doses that decreased lever-pressing in the post-training signal attenuation procedure (0.036 and 0.05 mg/kg) had a similar effect in regular extinction, whereas an SCH 23390 dose that decreased compulsive lever-pressing in the post-training signal attenuation procedure (0.01 mg/kg) had no effect on regular extinction. On the basis of electrophysiological data on the response of dopamine neurons to the omission of an expected reward, these results were interpreted as suggesting that compulsive lever-pressing depends on a phasic decrease in the stimulation of D(1) receptors. The implications of these results for the pathophysiology and treatment of obsessive-compulsive disorder are discussed.     

Factors associated with mortality and functional disability after hip fracture: an inception cohort study

Hip fracture results in excess mortality and functional disability. This study sought to identify predictors of mortality and limited functional ability 1 year after hip fracture. We conducted a 1-year follow-up of a prospective population-based inception cohort of 218 hip fracture patients who had been consecutively admitted and discharged from hospital during the previous year. Mortality was observed to be independently associated with poor mental status (relative risk [RR]=6.96; 95% confidence interval [95% CI], 1.73–28.00), prefracture limited functional ability (RR=4.35; 95% CI, 1.32–14.36), institutionalized disposition at discharge (RR=2.92; 95% CI, 1.02–8.38), and male gender (RR=2.44; 95% CI, 1.01–5.93). Independent predictors of limited functional ability were prefracture functional disability (RR=34.14; 95% CI, 3.13–372.33), poor mental status (RR=9.71; 95% CI, 1.57–59.82), age >80 years (RR=4.03; 95% CI, 1.48–11.00), and female gender (RR=3.57; 95% CI, 0.08–0.98). On discharge, special attention and care should thus be given to all patients displaying any of the above predictive factors.     

Monoclonal antibody production to human and bovine 2′:3′-cyclic nucleotide 3′-phosphodiesterase (CNPase): high-specificity recognition in whole brain acetone powders and conservation of sequence between CNP1 and CNP2

Monoclonal antibodies against human and bovine 2′:3′-cyclic nucleotide 3′-phosphodiesterase (CNPase) were generated by fusing FOX-NY myeloma cells with spleen cells from RBF/Dn mice previously immunized with the purified brain antigens. The enzyme isolated from bovine brain was quite basic, with an isoelectric point of 9.71 and both the bovine and human enzymes consisted of a closely spaced doublet at approximately 44 and 46 kDa on SDS-PAGE. Six monoclonals were identified as strongly recognizing the enzyme on both ELISA plates and on immunoblots of whole brain protein. Four monoclonals very weakly cross-reacted with guinea pig myelin basic protein. In contrast with two previous reports, some of our monoclonal antibodies did immunostain 2 or 3 protein bands in peripheral nerve, two bands closely corresponding to those immunostained in central nervous system (CNS) myelin, the Wolfgram protein fraction and in acetone powders of whole brain. Each of the 6 monoclonals reacting strongly on immunoblots recognized the enzyme in from 2 to 5 of the species examined (human, bovine, rat, mouse and rabbit). In addition, all 6 monoclonals that immunostained the enzyme in whole brain, myelin and Wolfgram protein immunoblots recognized both CNP1 (44 kDa) and CNP2 (46 kDa). The two closely spaced protein bands observed on SDS-PAGE and previously stained on immunoblots of CNS CNPase using polyvalent rabbit anti-bovine CNPase antisera, and now different monoclonal antibodies, appear to be immunologically related and to contain highly conserved sequences.