Prognostic implications of paranoia and thought disorder in new onset psychosis

This study follows a group of 174 young people with new onset of schizotypal symptoms and examines factors which may lead to conversion to psychosis. These prodromal subjects were screened for symptoms and later given the Structured Clinical Interview of DSM-III-R at one year, two years and ten years post onset. We also included the Paranoia Scale of Fenigstein and Vanable and the Scale for Thought, Language and Communications of Andreasen in all interviews. Our analysis found that the addition of scales for paranoia and thought disorder enhanced prediction of conversion to psychosis and long term outcome. The early occurrence of ideas of reference and poverty of thought appear to be significant predictors of future deterioration even when considered among other high-risk variables.     

Asymmetric dimethylarginine and reactive oxygen species: unwelcome twin visitors to the cardiovascular and kidney disease tables

Plasma levels of asymmetric dimethylarginine or markers of reactive oxygen species are increased in subjects with risk factors for cardiovascular disease or chronic kidney disease. We tested the hypothesis that reactive oxygen species generate cellular asymmetric dimethylarginine that together cause endothelial dysfunction that underlies the risk of subsequent disease. Rat preglomerular vascular smooth muscle cells transfected with p22(phox) had increased NADPH oxidase activity, enhanced activity and expression of protein arginine methyltransferase, and reduced activity and protein expression of dimethylarginine dimethylaminotransferase and of cationic amino acid transferase 1 resulting in increased cellular levels of asymmetric dimethylarginine. Rats infused with angiotensin II had oxidative stress. The endothelial function of their mesenteric arterioles was changed from vasodilatation to vasoconstriction, accompanied by increased vascular asymmetric dimethylarginine. All of these changes were prevented by Tempol. In vivo silencing of dimethylarginine dimethylaminotransferase 1 increased plasma levels of asymmetric dimethylarginine, whereas silencing of dimethylarginine dimethylaminotransferase 2 impaired endothelial function. We suggest that initiation factors, such as angiotensin II, expressed in blood vessels or tissues of subjects with cardiovascular and kidney disease risk factors generate reactive oxygen species from NADPH oxidase that enhances cellular asymmetric dimethylarginine in an amplification loop. This leads to adverse changes in vascular and organ functions, as a consequence of reduced tissue levels of NO and increased reactive oxygen species. Thus, we conclude that reactive oxygen species and asymmetric dimethylarginine form a tightly coupled amplification system that translates cardiovascular/kidney risk into overt disease.     

Exacerbation of pulmonary fibrosis following single lung transplantation

Acute exacerbations of interstitial lung disease present as clinical deteriorations, with progressive hypoxemia and parenchymal consolidation not related to infection, heart failure or thromboembolic disease. Following single lung transplantation, patients receive maintenance immunosuppression, which could mitigate the development of acute exacerbations in the native lung. A 66-year-old man with fibrotic, nonspecific interstitial pneumonitis presented with fever, hypoxemia and parenchymal consolidation limited to the native lung four years after single lung transplantation. Investigations were negative for infection, heart failure and thromboembolic disease. The patient worsened over the course of one week despite broad-spectrum antimicrobial therapy, but subsequently improved promptly with augmentation of prednisone dosed to 50 mg daily and addition of N-acetylcysteine. Hence, the patient fulfilled the criteria for a diagnosis of an acute exacerbation of pulmonary fibrosis in his native lung. Clinicians should consider acute exacerbation of parenchymal lung disease of the native lung in the differential diagnosis of progressive respiratory deterioration following single lung transplantation for pulmonary fibrosis.