A randomized controlled trial of a smoking cessation intervention among people with a psychotic disorder

OBJECTIVE: Despite extremely high rates of smoking among individuals with psychotic disorders and the associated financial and health costs, few studies have investigated the efficacy of smoking cessation interventions among this group. The purpose of this study was to compare an integrated psychological and nicotine replacement therapy intervention for people with a psychotic disorder with routine care alone. METHOD: The authors recruited 298 regular smokers with a psychotic disorder residing in the community and randomly assigned them to a routine care comparison condition (N=151) or an eight-session, individually administered smoking cessation intervention (N=147), which consisted of nicotine replacement therapy, motivational interviewing, and cognitive behavior therapy. Outcome variables included continuous and point-prevalence abstinence rates, smoking reduction status, and changes in symptoms and functioning. RESULTS: While there were no overall differences between the treatment group and comparison group in abstinence rates, a significantly higher proportion of smokers who completed all treatment sessions stopped smoking at each of the follow-up occasions (point-prevalence rates: 3 months, 30.0% versus 6.0%; 6 months, 18.6% versus 4.0%; and 12 months, 18.6% versus 6.6%). Smokers who completed all treatment sessions were also more likely to have achieved continuous abstinence at 3 months (21.4% versus 4.0%). There was a strong dose-response relationship between treatment session attendance and smoking reduction status, with one-half of those who completed the intervention program achieving a 50% or greater reduction in daily cigarette consumption across the follow-ups, relative to less than one-fifth of the comparison subjects. There was no evidence of any associated deterioration in symptoms or functioning. CONCLUSIONS: These findings demonstrate the utility of a nicotine replacement therapy plus motivational interviewing/cognitive behavior therapy smoking cessation intervention among individuals with a psychotic disorder. Further development of more efficacious interventions is required for those who do not respond to existing interventions.     

Doppler-defined pulmonary hypertension and the risk of death in children with sickle cell disease followed for a mean of three years

Pulmonary hypertension (PH) is associated with increased mortality in adults with sickle cell disease (SCD), but its prognostic significance in children is unknown. Eighty-eight children with SCD were followed after echocardiographic screening for PH. After a mean follow-up of 3 years, all 18 subjects with PH were alive. In our children, as in adults with SCD, PH was associated with increased haemolysis. In contrast, our subjects with PH did not have overt systemic disease observed in adults. PH may be a manifestation of progressive organ damage from chronic haemolysis and systemic vasculopathy that ultimately leads to early death in adulthood.     

Region-specific regulation of inflammation and pathogenesis in experimental autoimmune encephalomyelitis

Experimental autoimmune encephalomyelitis (EAE) is an animal model of multiple sclerosis and is characterized by an infiltrate of predominantly T cells and macrophages in the spinal cord and brain. In both the spinal cord and the cerebellum, Th1 cells direct inflammation to antigen-rich white matter tracts, and there is a TNFR1-dependent recruitment of CD11b(hi) cells in both regions. In the spinal cord, parenchymal invasion, demyelination and clinical symptoms are associated with TNFR1-dependant parenchymal induction (especially astrocytes) of VCAM-1 and CXCL2. None of these events occur in the cerebellum despite the fact that an inflammatory infiltrate accumulates in the perivascular space. Therefore regional specificity in astrocyte responses to inflammatory cytokines may regulate regional parenchymal infiltration and pathogenesis.     

A pilot study of hormone modulation as a new treatment for mania in women with bipolar affective disorder

We tested and compared the use of two adjunctive hormonal agents, tamoxifen and medroxyprogesterone acetate (MPA), for the treatment of acute mania or hypomania. A total of 13 women with acute Bipolar Affective Disorder in the manic or hypomanic phase were recruited from a clinical population to participate in this 28-day, three-arm, double blind, placebo-controlled study. The women who received tamoxifen exhibited significant improvement in symptoms of mania from baseline to final assessment compared with the placebo group. The MPA group improved more than the placebo group. Further exploration of tamoxifen as a useful adjunct in the treatment of acute manic symptoms in women with Bipolar Affective Disorder is warranted.     

Family matters: Maternal and litter-size effects on immune parameters in young laboratory rats

A functional immune system is important for the survival of mammalian young, particularly at weaning when they lose the immunological support provided by the mother’s colostrum and milk. In altricial mammals, litter size and maternal characteristics are important components of an animal’s early environment, which affect postnatal growth and development. In a study of unculled litters of Long-Evans laboratory rats (Rattus norvegicus), we asked whether such parameters are also associated with the immune status of the young shortly before weaning. On postnatal day 17, we assessed numbers of several leukocyte and lymphocyte subsets, the activity of the complement system, and immunoglobulin G (IgG) concentrations in the serum. Averaging the values of all pups per litter, we found negative correlations between litter size and lymphocyte counts, complement system activity and IgG concentration. Maternal effects were seen in the positive correlation between maternal postpartum body mass and granulocyte and monocyte counts. In addition, lymphocyte and monocyte counts as well as complement activity were lower for the young of multiparous than of primiparous mothers. This suggests a trend towards a better developed immune system in such offspring, which may be relevant for their immediate and long-term survival. The effects described here have potential implications for the design and interpretation of biomedical studies of immune parameters in laboratory rats.     

Cortical stimulation for language mapping in focal epilepsy: Correlations with tractography of the arcuate fasciculus

Purpose: Diffusion tensor imaging (DTI) provides information about magnitude (diffusivity) and directionality (fractional anisotropy, FA) of water diffusion and allows visualization of major white matter tracts. The arcuate fasciculus (AF) connects anterior (Broca’s) and posterior (Wernicke’s) language areas. We hypothesized that essential language areas identified by direct cortical stimulation would colocalize with areas revealing subcortical connectivity via the AF. Methods: Fourteen patients with pharmacoresistant left hemispheric epilepsy and left hemisphere language dominance underwent invasive evaluations for localization of epileptogenicity and functional mapping. DTI and T1‐weighted volumetric magnetic resonance imaging (MRI) scans were coregistered, and subdural grid electrodes identified on postimplantation computed tomography (CT) scans were also coregistered to the MRI scans. The AF was reconstructed from a region lateral to the corona radiata on the FA map. Colocalization, defined as <1 cm between the AF and the electrode positions delineating language cortex, was visually assessed with excellent reliability (Cronbach’s alpha = 0.98). Results: A total of 71 subdural grid contacts were overlying language cortex. Nineteen contacts in eight patients were over Broca’s area, 16 of which (84.2%) colocalized with the AF. Fifty‐two contacts in 10 patients were over Wernicke’s area, with colocalization in 29 patients (55.8%). Colocalization was significantly greater in anterior regions than in posterior regions [χ²(1) = 4.850, p < 0.05]. Discussion: The AF, as visualized with DTI, colocalized well with anterior language areas, but less so with posterior language areas, inferring that the latter are more spatially dispersed.     

Does MRI predict pathologic tumor response in women with breast cancer undergoing preoperative chemotherapy?

BACKGROUND: Neoadjuvant chemotherapy precludes the accurate pre-surgical pathologic measurement of tumor size. The purpose of this study is to review imaging studies performed in patients who received preoperative chemotherapy prior to surgery and determine whether MRI, ultrasound (US) or physical exam best predicted final pathologic tumor size. METHODS: Stage I, II, and III breast cancer patients were treated with neoadjuvant therapy on trial. As part of the trials, women underwent MRI, US, and physical exam prior to the start of therapy and 1 week after completion of neoadjuvant chemotherapy. RESULTS: Of the 68 patients with MRI data, the correlation coefficient (r) of MRI to pathologic size of tumor was r = 0.749. Among the 52 patients who had an US assessment the correlation of US to pathology was r = 0.612. Sixty-two patients had physical exam data, and the correlation of examination to pathology size was r = 0.439. MRI correctly predicted 8 of 11 complete responders and accurately evaluated the size of non-responders to neoadjuvant therapy (r = 0.869) CONCLUSIONS: In a select group of women undergoing neoadjuvant therapy for invasive breast cancer, MRI best predicted pathology response. The use of MRI in neoadjuvant therapy may allow for accurate prediction of patients eligible for breast conservation.     

In vivo age dependency of unfractionated heparin in infants and children

INTRODUCTION: Unfractionated Heparin (UFH) is used widely in paediatrics. Paediatric specific recommendations for UFH therapy are few, with the majority of recommendations being extrapolated from adult practice. In vitro studies have shown that this practice may be suboptimal. This study aimed to improve the understanding of the impact of age upon UFH response in vivo. MATERIALS AND METHODS: This prospective, observational study, conducted in the Paediatric Intensive Care Unit (PICU), included: patients 16 years or younger; treated with UFH of at least 10 U/Kg/hr. Laboratory analysis included: Antithrombin, APTT, Anti-Xa, Anti-IIa and thrombin generation expressed as the Endogenous Thrombin Potential. Results were grouped according to patient age (i.e. <1, 1-5, 6-10 and 11-16 years). RESULTS: 85 patients received an equivalent mean UFH dose with a median duration of 3 days. Antithrombin levels were decreased compared to age-related norms in children up to 11 years of age. APTT results were comparable across the age-groups. The Anti-Xa results using two different assays showed a trend for lower values in younger children. All children less than one year old recorded Anti-Xa values outside the therapeutic range for heparin therapy, for both assays. There was a trend for decreased Anti-IIa activity in younger children. Endogenous Thrombin Potential showed a significant trend for increased inhibition in older children. In vitro Antithrombin supplementation did not change the Anti-Xa or thrombin generation. CONCLUSIONS: This study confirms that, in vivo, for the same dose of UFH, the anti Xa and anti IIa effect, as well as the inhibition of endogenous thrombin potential is age dependent and that these differences are not purely AT dependent. The implication is that the anticoagulant and antithrombotic effect of a given dose of UFH differs with age. Clinical outcome studies to determine the optimal dosing for each age group are warranted.     

Semaphorin 5B is a novel inhibitory cue for corticofugal axons

Neuronal connectivity is generated by the precise guidance of neuronal growth cones in response to the spatiotemporal distribution of molecular guidance cues in the developing embryo. Here we show that the class 5 semaphorin, Semaphorin 5B, is expressed in regions of the cortex and subcortex flanking the projection of and avoided by descending cortical axons, suggesting a role as a repulsive guidance cue in the formation of the internal capsule. Axons from cortical explants cultured in vitro with Semaphorin 5B-expressing cells exhibited characteristic avoidance behaviors. In organotypic slices, ectopic Semaphorin 5B expression along the presumptive internal capsule was sufficient to cause cortical axons to avoid their normal trajectory, resulting in either stalling at the boundary of Semaphorin 5B or turning into inappropriate areas of the cortex. In contrast, thalamocortical axons were not inhibited either in vitro or in slice culture by ectopic Semaphorin 5B. To further examine the function of Semaphorin 5B in situ, we knocked down its expression in the ventricular zone (VZ) at the corticostriatal angle. We found that labeled cortical fibers aberrantly navigated into the VZ where Semaphorin 5B expression was reduced. We propose that Semaphorin 5B functions to prevent corticofugal axons from abnormally projecting into germinal regions as they project to their subcortical targets.