Distribution of temperature changes and neurovascular coupling in rat brain following 3,4‐methylenedioxymethamphetamine (MDMA, “ecstasy”) exposure

(+/?)3,4‐methylenedioxymethamphetamine (MDMA, “ecstasy”) is an abused psychostimulant that produces strong monoaminergic stimulation and whole‐body hyperthermia. MDMA‐induced thermogenesis involves activation of uncoupling proteins (UCPs), primarily a type specific to skeletal muscle (UCP‐3) and absent from the brain, although other UCP types are expressed in the brain (e.g. thalamus) and might contribute to thermogenesis. Since neuroimaging of brain temperature could provide insights into MDMA action, we measured spatial distributions of systemically administered MDMA‐induced temperature changes and dynamics in rat cortex and subcortex using a novel magnetic resonance method, Biosensor Imaging of Redundant Deviation in Shifts (BIRDS), with an exogenous temperature‐sensitive probe (thulium ion and macrocyclic chelate 1,4,7,10‐tetraazacyclododecane‐1,4,7,10‐tetramethyl‐1,4,7,10‐tetraacetate (DOTMA^4?)). The MDMA‐induced temperature rise was greater in the cortex than in the subcortex (1.6 ± 0.4 °C versus 1.3 ± 0.4 °C) and occurred more rapidly (2.0 ± 0.2 °C/h versus 1.5 ± 0.2 °C/h). MDMA‐induced temperature changes and dynamics in the cortex and body were correlated, although the body temperature exceeded the cortex temperature before and after MDMA. Temperature, neuronal activity, and blood flow (CBF) were measured simultaneously in the cortex and subcortex (i.e. thalamus) to investigate possible differences of MDMA‐induced warming across brain regions. MDMA‐induced warming correlated with increases in neuronal activity and blood flow in the cortex, suggesting that the normal neurovascular response to increased neural activity was maintained. In contrast to the cortex, a biphasic relationship was seen in the subcortex (i.e. thalamus), with a decline in CBF as temperature and neural activity rose, transitioning to a rise in CBF for temperature above 37 °C, suggesting that MDMA affected CBF and neurovascular coupling differently in subcortical regions. Considering that MDMA effects on CBF and heat dissipation (as well as potential heat generation) may vary regionally, neuroprotection may require different cooling strategies. Copyright © 2015 John Wiley & Sons, Ltd.     

Intramuscular ziprasidone treatment of acute psychotic agitation in elderly patients with schizophrenia.

OBJECTIVE: Intramuscular (i.m.) ziprasidone treatment has been shown to be effective and well tolerated in reducing the symptoms of acute psychosis in adults. Few data are available as to safety in the elderly. The growing utilization of health services by elderly psychiatric patients warrants an evaluation in this population. METHOD: Consecutive elderly patients (60 years of and older) admitted to a psychogeriatric ward in a large, university-affiliated tertiary psychiatric center were treated by i.m. ziprasidone for acute psychotic agitation. Patients received three days of flexible-dose i.m. ziprasidone. After an initial dose of 10-20 mg, a subsequent dose of 10-20 mg could be given after 12 hours if needed (maximum daily dose: 40 mg). RESULTS: All treatment emergent side effects and adverse events along with the investigators' assessments of severity were systematically recorded as the primary outcome. The Brief Psychiatric Rating Scale (BPRS) and the Behavioral Activity Rating Scale (BARS) were the secondary outcomes. Twenty-one patients, six male and 15 female, mean age 71.4 +/- 1.3 years (range: 60-81 years) were enrolled. All had completed the three days i.m. ziprasidone treatment. There was one adverse event in a patient with untreated benign prostatic hypertrophy who developed urinary retention. Two side effects of mild severity that resolved spontaneously were observed: blurred vision and sedation. The BPRS decreased by 26.8 points after three days of treatment (p = 0.001). The BARS score, reflecting agitation, decreased significantly after each injection, reaching maximal decrease of 2.14 points at completion of study (p = 0.001). CONCLUSION: Intramuscular ziprasidone in this series of elderly patients suggests acceptable safety and efficacy in the management of acute psychotic agitation among elderly patients with schizophrenia.     

Primary gastrointestinal lymphomas in Turkey: a retrospective analysis of clinical features and results of treatment.

Thirty-three patients with primary gastrointestinal lymphoma (GIL) followed at Ankara University Medical School have been evaluated. The most frequent locations of the disease are the small intestine (48.4%) and the stomach (39.3%). The intermediate and high grade lymphomas constitute 84.8% of the cases. The mean age of the patients with small intestinal lymphoma is 28.7 years and 47.1 years for those with gastric lymphoma. The patients treated with surgery and chemotherapy (S+CT) have a longer survival than those treated with chemotherapy (CT) alone. In conclusion: 1) Small intestinal lymphoma occurs more frequently than gastric lymphoma in our study. 2) The median age of the Turkish patients with primary GIL is approximately 10 years less than those in the Western countries. 3) The therapeutic results of S+CT are superior to those of CT in the early stages of the disease.     

Inter-NICU variation in rates and management of thrombocytopenia among very low birth-weight infants.

OBJECTIVES: To investigate variation among neonatal intensive care units (NICUs) in prevalence and management of thrombocytopenia in infants <1500 g. STUDY DESIGN: In total 1283 infants &<1500 g admitted to six NICUs over 21 months were prospectively analyzed. Illness severity was measured by the Score for Neonatal Acute Physiology (SNAP). Platelet counts in the first 12 hours after birth and on day 3 of life were abstracted from the infants' medical records. Thrombocytopenia was determined from the lowest platelet count in each of these time periods. RESULTS: There was variability in rates of thrombocytopenia among NICUs, even after controlling for risk factors (e.g., SNAP, small for gestational (SGA) age and maternal hypertension). One site had a high prevalence of thrombocytopenia, but the lowest percentage of infants with thrombocytopenia who received platelet transfusions. After controlling for SNAP, GA, SGA, Apgar score and incidence of thrombocytopenia, the odds of receiving platelets at this site, relative to the site with the highest transfusion rate, was 0.10 (95% CI 0.02 to 0.43). CONCLUSIONS: This multicenter study finds a 10-fold variation among NICU in the administration of platelets to their thrombocytopenic infants that cannot be explained by presence of thrombocytopenia or illness severity.     

Mental retardation and psychiatric illness.

Although traditional diagnostic criteria are accepted for use with mentally retarded persons, diagnosis of psychiatric disorders in this population is often complicated by clinicians' ignoring or underestimating such disorders and by patients' communication problems. The revision of DSM-III and changes in policies of third-party payers have sensitized clinicians to the presence of psychopathology among mentally retarded persons. The authors discuss the relationship between mental illness and mental retardation and review recent research on the diagnosis of specific psychiatric disorders in these patients. Some problems, such as behavioral disruptiveness, psychoses, and phobias, are more prevalent among mentally retarded persons than among other populations, whereas other problems, such as alcoholism and suicide, may be less common.     

Edematous syndromes caused by capillary hyperpermeability. Diffuse angioedema

Edema due to increased capillary permeability (ICP) may be diffuse or localized. Local edemas (Quincke edema, angioneurotic edema) are most often allergic or very rarely due to a defect in C1-inhibitor. Generalized edemas due to ICP share the following clinical features: Fluid retention (subcutaneous edema and diffused swelling) is predominant in lower limbs; it is worsened by orthostatism and warmth and alleviated by decubitus and cold, with important weight variations between morning and evening. It is associated with enhanced thirst, hypotension, oliguria, headaches and blood volume reduction; secondary hyperaldosteronism is the main mechanism. These troubles are due to ICP, associated with lymphatic drainage abnormalities; ICP is measured by the isotopic Landis Test. This abnormality is present in several diseases. Idiopathic orthostatic edema (IOE) is frequent and often unrecognized, occurring mainly in women, often associated with luteal insufficiency. Iatrogenic complications (diuretic and laxative abuses) are frequently superimposed. ICP may be corrected by vitamins P (rutin, anthocyanosides, diosmin, Ginkgo biloba extracts...) Cyclic shock due to ICP is rare. It is characterized by cyclic edema and shock with hypovolemia, hypoproteinemia; the mechanism of shock is a severe loss of fluid and protein from the vascular bed. It is often associated with monoclonal gammapathy and complement activation. In our personal case, the trouble in CP was present all along the disease with permanent edema and low blood pressure (especially in orthostatism). Vit "P" and Ginkgo biloba extracts were able to partially improve CP and the clinical troubles. However, in spite of this treatment a fatal shock occurred after ten years follow-up. Episodic angioedema associated with eosinophilia was first described by Gleich.(ABSTRACT TRUNCATED AT 250 WORDS)     

Obsessive-compulsive disorder in mentally retarded patients

Of 283 mildly to profoundly retarded patients, 10 (3.5%) presented with compulsive behavior that significantly interfered with their daily functioning. Compulsions occurred in the context of obvious cerebral dysfunction and in the absence of anxiety or "ego-dystonic" qualities. The interrater reliability of the differential diagnosis between compulsions, stereotypies, and other repetitive behaviors was good (kappa = .82). A severity rating scale for the compulsive behavior yielded total scores with good interrater reliability (intraclass correlation coefficient = .82). Single items that described observable behaviors had good reliability, while inner resistance and subjective distress were not reliably assessed and contributed little to the total score. The authors suggest that the DSM-III-R diagnosis of obsessive-compulsive disorder be considered in mentally retarded patients, despite the absence of recognizable ego dystonic characteristics. Emphasis should be on the behavioral, externally observable components of the disorder, rather than on inner conflicts and anxiety. Such a diagnostic approach may also benefit nonretarded compulsive patients.     

Multicontrast MRI of remyelination in the central nervous system

Although magnetic resonance imaging (MRI) represents the most sensitive tool for the detection of white matter abnormalities in patients with multiple sclerosis (MS), the heterogeneity of MS placques severely hampers the elucidation of specific pathophysiological processes. In order to identify putative MRI markers for de- and remyelination, we employed the cuprizone mouse model which leads to a selective and reversible demyelination of the corpus callosum with little or no axonal damage. Apart from histopathology, animals were studied with high-resolution three-dimensional MRI in vivo using multiple contrasts. While individual MRI findings significantly correlated with electron microscopy, the differentiation of regions with normal, demyelinated or remyelinated white matter by one contrast alone was less specific than by histology or electron microscopy. However, an accurate MRI prediction of the in vivo myelin status was achieved by a discriminant function analysis using a combination of T1, T2 and magnetization transfer contrast. With a correct assignment of 95% of all animals examined, the procedure will allow for the survey of new therapeutic approaches aiming at improved remyelination.     

Anti-idiotypic IgM antibodies to anti-HLA class I antibodies in habitual abortion.

In order to investigate the role of the idiotypic network in miscarriages, sera from 28 habitually aborting women undergoing paternal leukocyte immunization were studied for the presence of HLA antibodies and related anti-idiotypes. Sixty-eight percent of sera from preimmunized patients which did not contain anti-lymphocyte antibodies inhibited the activity of antibodies to the HLA class I antigens expressed by the spouse. This inhibitory activity could be assigned to IgM antibodies, which cross-inhibit antibodies of similar specificity. This suggests that they are anti-idiotypes for the binding site of HLA antibodies. Immune sera of successfully treated patients exhibited both cytotoxic IgG anti-HLA antibodies and inhibitory IgM anti-idiotypic antibodies. A possible role for an intact idiotypic network in maintaining pregnancy is suggested.     

Exploring the potential association among sleep disturbances,cognitive impairments,and immune activation in 22q11.2 deletion syndrome

22q11.2 deletion syndrome (22q11.DS) is a neurogenetic disorder caused by a microdeletion in chromosome 22. Its phenotype includes high rates of psychiatric disorders, immune system abnormalities, and cognitive impairments. We assessed the quality of sleep in 22q11.2DS and its potential link to inflammatory markers and cognitive deficits. Thirty‐three 22q11.2DS individuals and 24 healthy controls were studied. Sleep parameters were assessed by the Pittsburgh sleep quality index (PSQI) questionnaire and correlated with serum cytokine levels and cognitive functioning, measured using the Penn computerized neurocognitive battery (CNB). The 22q11.2DS individuals had significantly worse sleep quality scores than the controls, unrelated to the psychiatric or physical comorbidities common to 22q11.2DS. Interleukin 6 levels were correlated with the overall score of the PSQI questionnaire for nonpsychotic 22q11.2DS participants only. Several domains of the CNB were associated with poorer sleep quality, suggesting that cognitive impairments in 22q11.2DS may be at least partially explained by poor sleep quality. Our findings confirm sleep impairments in individuals with 22q11.2DS, which might negatively affect their cognitive functioning, and corroborate a potential role of immunological pathways in the 22q11.2DS neuro‐phenotype.