OBJECTIVES:To describe diagnosis, CT findings, management and short-term outcome of a large population of canine pyothorax cases.METHODS:Retrospective analysis of 101 canine pyothorax cases at two UK referral centres. Medical records and CT images were reviewed. Dogs were included if pre- and post-contrast CT was performed within 48 hours of presentation.RESULTS:CT abnormalities included pleural thickening (84.1%), pannus (67.3%), pneumothorax (61.4%), mediastinal effusion (28.7%), pulmonary (13.8%) and mediastinal (7.9%) abscessation, foreign body presence (7.9%), foreign body tracts (6.9%) and pneumonia (6.9%). Seventy-one percent of dogs were managed surgically, of which 90.2% survived, and 29% were managed medically, of which 72.4% survived. Overall mortality was 14.8% and 86.6% of these dogs died within 48 hours of admission. All dogs with evidence of a foreign body on CT underwent surgery.CLINICAL SIGNIFICANCE:Mortality in our population was low and most dogs that died did so within 48 hours of hospitalisation, regardless of management type.

Painful diabetic neuropathy (PDN) is an intractable complication of diabetes that affects 25% of patients. PDN is characterized by neuropathic pain and small-fiber degeneration, accompanied by dorsal root ganglion (DRG) nociceptor hyperexcitability and loss of their axons within the skin. The molecular mechanisms underlying DRG nociceptor hyperexcitability and small-fiber degeneration in PDN are unknown. To delineate the molecular mechanisms behind nociceptor hyperexcitability and small-fiber degeneration, it becomes important to uniquely identify changes in the nociceptor population from within the heterogeneous population of neurons in the DRG. To identify genes that are differentially expressed in PDN, we compared the RNA profile of mice fed a regular-diet (RD) or a high-fat diet (HFD), a commonly used model of PDN. To capture the translational state of these nociceptive neurons, we used transgenic mice expressing tagged ribosomal subunits (RiboTag) in the nociceptor population expressing the sodium channel-Nav1.8. Analysis of the RiboTagged mRNA between HFD and RD mice at 10 weeks revealed 84 upregulated genes and 70 downregulated genes. We identified candidate genes like ApoD, known to increase excitatory signaling through CXCR4/CXCL12. Previously our work demonstrated that CXCR4/CXCR12 signaling is critical for the development of mechanical allodynia and small-fiber degeneration in PDN. Further analysis implicated changes in pathways relating to extracellular matrix organization, gliogenesis and, complex 1 biogenesis. In addition to the translational profiling, we plan to perform single-cell RNA sequencing of the Nav1.8-positive DRG neuron population using Nav1.8-Cre;Ai9 mice fed an RD or an HFD. Single-cell RNA sequencing will give us a better understanding of the transcriptional status of subpopulations within the Nav1.8-positive DRG neurons and generate candidate genes at a higher resolution. This study will provide insight into the genes that are involved in the pathogenesis of neuropathic pain and small-fiber degeneration and yield potential translational targets for disease-modifying treatments for PDN. Painful diabetic neuropathy (PDN) is an intractable complication of diabetes that affects 25% of patients. PDN is characterized by neuropathic pain and small-fiber degeneration, accompanied by dorsal root ganglion (DRG) nociceptor hyperexcitability and loss of their axons within the skin. The molecular mechanisms underlying DRG nociceptor hyperexcitability and small-fiber degeneration in PDN are unknown. To delineate the molecular mechanisms behind nociceptor hyperexcitability and small-fiber degeneration, it becomes important to uniquely identify changes in the nociceptor population from within the heterogeneous population of neurons in the DRG. To identify genes that are differentially expressed in PDN, we compared the RNA profile of mice fed a regular-diet (RD) or a high-fat diet (HFD), a commonly used model of PDN. To capture the translational state of these nociceptive neurons, we used transgenic mice expressing tagged ribosomal subunits (RiboTag) in the nociceptor population expressing the sodium channel-Nav1.8. Analysis of the RiboTagged mRNA between HFD and RD mice at 10 weeks revealed 84 upregulated genes and 70 downregulated genes. We identified candidate genes like ApoD, known to increase excitatory signaling through CXCR4/CXCL12. Previously our work demonstrated that CXCR4/CXCR12 signaling is critical for the development of mechanical allodynia and small-fiber degeneration in PDN. Further analysis implicated changes in pathways relating to extracellular matrix organization, gliogenesis and, complex 1 biogenesis. In addition to the translational profiling, we plan to perform single-cell RNA sequencing of the Nav1.8-positive DRG neuron population using Nav1.8-Cre;Ai9 mice fed an RD or an HFD. Single-cell RNA sequencing will give us a better understanding of the transcriptional status of subpopulations within the Nav1.8-positive DRG neurons and generate candidate genes at a higher resolution. This study will provide insight into the genes that are involved in the pathogenesis of neuropathic pain and small-fiber degeneration and yield potential translational targets for disease-modifying treatments for PDN.

OBJECTIVES:To assess the prevalence of thrombocytopenia in a referral population of cats in the UK, to identify disease processes associated with thrombocytopenia and to assess the proportion of thrombocytopenic cats that tested positive for feline leukaemia virus or feline immunodeficiency virus.MATERIALS AND METHODS:Retrospective analysis of medical records at a UK referral hospital. Cats were grouped by mechanism of thrombocytopenia and disease process (where known).RESULTS:Prevalence of thrombocytopenia was 5·9%. The most common disease processes associated with thrombocytopenia were haematological or infectious disease and neoplasia; 11% of thrombocytopenic cats tested were positive for feline leukaemia virus, which is lower than reported previously. Cats presenting with unexplained haemorrhage had significantly lower platelet counts than other thrombocytopenic cats. Primary immune-mediated thrombocytopenia was less commonly diagnosed than in dogs and associated with the most severe platelet depletion in this study.CLINICAL SIGNIFICANCE:Thrombocytopenia in cats may be more prevalent than previously reported and severe thrombocytopenia may be associated with spontaneous haemorrhage. Severe thrombocytopenia in cats appears less commonly immune-mediated than in dogs. Thrombocytopenia did not appear to be associated with retroviral infections.

The concept of open-ended groups is expanded to include an open-door model (OEOD) wherein members with severe mental illnesses, including schizophrenia disorders and bi-polar, can join, leave, and re-enter groups as their life circumstances dictate their availability and willingness for treatment. This model is grounded on the work of Schopler and Galinsky's (1984/2006) and Galinsky and Schopler's (1989) theses on the value and processes of open-ended groups and includes perspectives on mutual aid and group development. Groupwork with the OEOD format is illustrated with examples taken from a group of 79 participants diagnosed with first-episode schizophrenia/schizoaffective disorders, 40 of who had co-occurring substance abuse. Of the 79 participants in the OEOD group program, 70 (89%) remained in treatment for the maximum of 3 years. The over-all value of group treatment for this population is reviewed along with the small number of available publications on open-ended and open-door-type groups.

This chapter outlines the basic social services available to a schizophrenic patient on their way to recovery. The U.S. government provides Social Security benefits for the mentally ill; Medicaid, Medicare, and private medical insurance policies can help take care of outstanding medical bills. This chapter also contains plenty of tips and instructions on how to deal with questions of eligibility for these benefits, proceed with applications, and in worse cases, appeal to these service providers should a claim be denied. It is a patient’s responsibility, overall, to remain informed of the available services and seek advice from a case manager or similar, and apply for claims where applicable. The paperwork will doubtless be a long and arduous process, but the benefits will certainly be worth the trouble.

During the past two decades, the Child Psychiatry Branch at the National Institute of Mental Health has conducted a longitudinal study (including long-term prospective follow-up) of childhood-onset schizophrenia, a rare form of the disorder. Critical to this research has been accurate diagnosis. Outpatient screening has accurately diagnosed 55% of the 121 childhood-onset schizophrenia patients in the study to date. However, inpatient observation including drug-free observation has proven crucial to ruling out 96 children with alternative diagnoses who had been provisionally admitted for inpatient study. Standardized clinical ratings from outpatient screening only predicted 62% of these nonschizophrenia patients. Historically, medication-free observation was standard clinical care for difficult and unusual patients; this should be employed when possible in similar situations.

This chapter contains strategies on coping with the positive and negative symptoms of schizophrenia, as discussed in Chapter 4. For positive symptoms, taking medication consistently is the only effective way of dealing with such symptoms. Coping with symptoms before the medications take effect will likely be an issue, so it is best to keep the doctor abreast of further developments as well as maintain a healthy grasp of reality—and if failing the latter, the patinet should, of course, ask for further assistance. With negative symptoms, coping mechanisms are more varied, as they're geared towards improving the patient's drive and motivation for simply getting through the day or socializing with others. These will take practice—as far as improving the patient's conversational skills and the like go—but as with the positive symptoms, things will get easier over time.

This chapter chronicles the volunteer contributors’ lives to date as they continue to live with their schizophrenia. Not all of the anecdotes here are “success stories,” however, as many of the contributors still continue to cope with symptoms and other issues. Some of them still engage in unhealthy lifestyles, or are still searching for medications that can work for them, or they may simply have trouble with feeling like “themselves” again. Many still experience breakdowns and struggle with “staying sane,” while others notice considerable improvements to their health over time. Overall, these are stories of people trying to move on and cope with the dramatic changes in their lives as a result of their schizophrenia. These are stories meant to reassure rather than inspire, to point out that there is a life and a future beyond schizophrenia.

Introduction: The purpose of this study is to determine if an earlier age at onset of positive symptoms in schizophrenia is associated with cannabis use disorders (CUD).Methods: 49 first-episode schizophrenia subjects with CUD were compared to 51 first-episode schizophrenia subjects with no substance use disorders for demographic and clinical variables. A multivariate logistic regression was performed to determine the joint relationship between variables significantly associated with CUD on univariate testing and ascertain if these variables independently predict CUD. Significance level was set at p<0.05.Results: 74% of CUD subjects had the onset of CUD before the onset of positive symptoms. Compared to non-substance abusing subjects, CUD subjects were predominantly male, younger at study entry, had an earlier age at onset of positive symptoms, less educational attainment, a lower self-socioeconomic status, better premorbid childhood social adjustment, a trend for poorer premorbid childhood academic adjustment, less motor abnormalities but more severe hallucinations and delusions. In the multivariate analysis, only male gender, worse socioeconomic status, better premorbid childhood social adjustment, and more severe positive symptoms at study entry were associated with a lifetime history of CUD.Discussion: Although cannabis use precedes the onset of illness in most patients, there was no significant association between onset of illness and CUD that was not accounted for by demographic and clinical variables. Previous studies implicating CUD in the onset of schizophrenia may need to more comprehensively assess the relationship between CUD and schizophrenia, and take into account additional variables that we found associated with CUD. (C) 2010 Elsevier B.V. All rights reserved.

Correction to: Molecular Psychiatry advance online publication, 18 May 2010; doi: 10.1038/mp.2010.59 After the article was published online, the authors noted G Germain's name was incomplete in the author list. The corrected author list appears below: AM Addington, J Gauthier, A Piton, FF Hamdan, A Raymond, N Gogtay, R Miller, J Tossell, J Bakalar, G Inoff-Germain, P Gochman, R Long, JL Rapoport and GA Rouleau

Introduction: Although several studies have reported on cannabis use and adherence for first episode of psychosis patients, the findings remain unclear as to whether cannabis use is a risk factor for poor adherence in young people with first-episode schizophrenia. This study was designed to follow patients' use of cannabis and adherence in a naturalistic setting during the first 12 months of treatment. It examines whether cannabis use is a risk factor for two distinct types of non-adherence: non-adherence to medication and treatment dropout.Methods: Participants were 112 first-episode schizophrenia patients of diverse backgrounds a two community hospitals, enrolled in a study of differential effectiveness of two second generation antipsychotic medications. Multiple indicators were used to assess cannabis use and adherence to medication. Patients were encouraged to continue in the study even after period of treatment refusal or change from study to standardized medication. Study hypotheses were tested using Cox proportional hazards models with cannabis use as a time-varying covariate.Results: After 12 months, 23 had dropped out and 37 had at some point been non-adherent to medication. Of 34 participants who used cannabis during treatment, 32 had a prior diagnosis of cannabis abuse/dependence and 30 were male. Independently of age, race, socioeconomic status, gender, site, and medication assignment, cannabis use significantly increased hazard of non-adherence by a factor of 2.4 (p<.001) and hazard of dropout by a factor of 6.4 (p =.034)Conclusion: Results indicate that cannabis use is a risk factor for non-adherence to medication and dropout from treatment. Treatment for first-episode schizophrenia may be more effective if providers address the issue of cannabis use with patients throughout the early years of treatment, especially for those with existing cannabis abuse/dependence. Published by Elsevier B.V.

Schizophrenia is a debilitating brain disorder characterized by hallucinations, delusions, disordered thinking, diminished emotion, and cognitive impairment. Age of onset of schizophrenia is typically in late adolescence and early adulthood. Given a worldwide prevalence of approximately 1%, schizophrenia is the fourth leading cause of disability and major public health burden. Family, twin and adoption studies have demonstrated a large genetic component, with estimates of heritability around 81%.(1) Childhood onset schizophrenia is rare, with the prevalence estimated to be approximately 1/300th the rate of the more typical adult onset form. As has been the case for other complex disorders such as breast cancer and Alzheimer’s disease, the study of extreme early onset cases might facilitate the discovery of disease genes.(2) Since 1990, we have recruited and rigorously characterized 92 patients with COS.(3) None of these patients had notable dysmorphologies indicative of an obvious chromosomal anomaly. However, there was an increased rate of early pre-psychotic neurodevelopmental disorders relative to that seen in adult onset patients.(4) Such disorders are seen in many genetic syndromes of pediatric onset;(5) the mean IQ of this group was 80, somewhat lower than that of adult onset patients. Follow-up every 2 years for reevaluation confirms the stability of the diagnosis of schizophrenia and has shown continuity with the more common adult onset form of the disorder (AOS).(3, 6) Previously we reported that high resolution karyotyping and fluorescent in situ hybridization (FISH) revealed 4 cases with the typical 3 Mb 22q11 deletion,(7) 1 case with atypical Turner’s syndrome (46,X,del(X)(q24-ter),(8) and 1 case with an inherited 1;7 balanced translocation.(9) The rate of 4 out of 92 cases for 22q11 deletion is significantly higher than that seen in samples of unselected patients with AOS.(7) In addition, one case with 5q32-ter segmental uniparental isodisomy (35 Mb) was observed through loss of heterozygosity (LOH) on the Affymetrix NspI 250K SNP array and confirmed with genotyping of microsatellite markers.(10) Numerous case reports for Turner syndrome and trisomy X provide evidence for the increased risk of psychotic disorders and relevant psychopathological manifestations among adults with X-chromosome anomalies.(11–13) Unrelated studies report rates of atypical Turner syndrome in the general and adult psychiatric population to be 0.2% and 0.17%, respectively.(13, 14) Women with Turner syndrome also show impairments in emotional and visual-spatial processing, decreased full-scale IQ, and share similarities with schizophrenia patients in structural and functional brain abnormalities.(15, 16) Less is known about the association between trisomy X and psychosis; however DeLisi et al. reported the prevalence of trisomy X to be 0.63% in studies of adult onset schizophrenia compared to the 0.39% in the general population.(12, 17) Here we report 2 additional cases with X chromosome anomalies in the NIMH COS cohort: one mosaic Turner syndrome (46,X,i(X)(q10)(22%)/45,X(78%)), and one trisomy X (47, XXX), bringing the total prevalence to 3/38 (7.9%) among the females in this cohort. The prevalence of these X chromosome anomalies in the NIMH COS population is significantly greater than the reported rates in either the general population (0.2%) or adult onset schizophrenic populations (0.4%, p=0.001) (Table I). Table 1 Rates of specific sex chromosome anomalies in childhood onset schizophrenia (COS), adult onset schizophrenia (AOS), and general population samples Further, in accordance with Kaplan & Cotton’s (1968) hypothesis of “the possibility that other and more subtle genetic instabilities may be associated with the schizophrenic disorders,” we hypothesized that X-chromosome anomalies may be associated with previously unidentified micro-deletions and/or duplications that predispose to schizophrenia.(18) To test this hypothesis, we completed whole genome high density SNP and CGH arrays to ascertain novel structural variants (see details in Walsh et al 2008).(19) Briefly, Affymetrix Mapping 500K SNP arrays and Agilent 185K/244K oligo arrayCGH were completed according to manufacturer protocols (www.affymetrix.com, www.agilent.com) and only variants that were identified through both methods were considered for analysis. Results did not reveal any further de novo chromosomal events among the probands with X-chromosome anomalies that could be implicated in the etiology of schizophrenia. Nor did these cases tend to have a higher rate of rare structural variants as compared to karyotypically normal female COS probands (results not shown). However, the one case with atypical Turner syndrome who was missing part of one Xq arm was found to have also a 17 Mb duplication of chromosome 16q22.2-ter. Spectral karyotyping revealed that the extra copy of this segment of chromosome 16 was attached to the missing arm of the X chromosome. The duplicated region of chromosome 16 contains approximately 100 known genes, but presents an interesting case since it is not clear what the functionality of the derived chromosome X;16 would be. It is conceivable that the entire chromosome would be subject to X-inactivation, though functional studies would be warranted for this case. To summarize, this report confirms that subsyndromal sex chromosome anomalies in COS are significantly higher than that found in the community or in AOS. The role of these anomalies in schizophrenia is unclear, though dysregulation of emotional processing may be one component. While we had hypothesized that these cases may have other, more subtle submicroscopic structural variants that could be involved in schizophrenia etiology, this was not confirmed. To date, the overall rate of rate of large chromosomal abnormalities and 22q11 deletions among this COS cohort is 10%.