Assessment of biological, psychological and adherence factors in the prediction of step-down treatment for patients with well-controlled asthma.

BACKGROUND AND OBJECTIVE: Inhaled corticosteroids (ICS) and inhaled corticosteroids combined with long-acting beta2-agonist (ICS/LABA) are standard treatments for asthma. However, factors that might help reduce medication in well-controlled asthma are unknown. We classified problems of asthma patients into biological, psychological and adherence factors, and investigated factors associated with the indication and failure of a medication step-down treatment. METHODS: Two hundred twenty two well-controlled asthma patients receiving ICS or ICS/LABA were assessed for physical and psychiatric problems and followed up for one year from adjustment of their treatment step. Factor B was defined as a presence of chronic upper airway complications. Factor P was defined as presence of psychiatric complications such as sleep disorder, depression, anxiety and somatoform disorders. Factor A was defined as poor adherence to ICS or ICS/LABA inhaler of 75% or less. Success in step-down treatment was defined as maintenance of well-controlled status for over one year after step-down. RESULTS: Factor B was the most important single negative predictive factor for indication for step-down treatment (Odds ratio; 0.19). Factor A increased the risk of failure to maintain step-down treatment most significantly by 23-fold, and factor B increased it by 11-fold. The combination of factors B and A increased failure by 24-fold, factors P and A by 21-fold, all three factors by 36-fold. Factor P only interacted with the other factors to reduce chances of stepping down, but did not constitute a problem factor when present alone. CONCLUSION AND CLINICAL RELEVANCE: The evaluation of biological, psychological and adherence problems may lead to a more proactive and targeted approach to step-down treatment for patients with well-controlled asthma.

Retinoic acids up-regulate functional eosinophil-driving receptor CCR3.

Eotaxins and their receptor CCR3 have a definitive role for tissue accumulation of eosinophils both under homeostatic and pathologic conditions. However, physiological stimuli that can up-regulate CCR3 in blood-derived human eosinophils have not been recognized. As a prior gene microarray study revealed up-regulation of CCR3 in eosinophils stimulated with retinoic acids (RAs), the expression of functional CCR3 was examined. We found that 9-cis RA and all-trans RA (ATRA) significantly induced surface CCR3 expression regardless of the presence of IL-3 or IL-5. Pharmacological manipulations with receptor-specific agonists and antagonists indicated that retinoic acid receptor-α activation is critical for CCR3 up-regulation. RA-induced CCR3 was associated with its functional capacity, in terms of the calcium mobilization and chemotactic response to eotaxin-1 (CCL11). Our study suggests an important role of vitamin A derivatives in the tissue accumulation of eosinophils.

Contribution of sodium valproate to the syndrome of inappropriate secretion of antidiuretic hormone.

We report the case of a 62-year-old man who was administered sodium valproate (VPA) and who subsequently developed the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). He had been taking VPA for treatment of idiopathic generalized tonic-clonic convulsions since he was 56 years old. After substituting VPA with zonisamide, the serum sodium level returned to normal. We consider this episode of SIADH to be the result of a combination of factors including a weakness of the central nervous system and the long-term administration of VPA.

Schizophrenia-associated idiopathic unconjugated hyperbilirubinemia (Gilbert's syndrome).

BACKGROUND: Idiopathic unconjugated hyperbilirubinemia (Gilbert's syndrome) is a benign hyperbilirubinemia found in the general population. There has been only 1 previous report of Gilbert's syndrome occurring in schizophrenic patients. The present study was conducted to determine the frequency of Gilbert's syndrome in schizophrenic patients relative to patients with other psychiatric disorders. METHOD: Plasma bilirubin concentrations of every patient admitted to the psychiatric hospital during a 3-year period were collected, and patients were examined to exclude all other causes of hyperbilirubinemia. In addition, the psychiatric symptoms of schizophrenic patients (ICD-10 criteria) with hyperbilirubinemia were evaluated by the Positive and Negative Syndrome Scale (PANSS). RESULTS: Schizophrenic patients showed a significantly higher incidence of hyperbilirubinemia (p < .05) relative to patients suffering from other psychiatric disorders, and schizophrenic patients with hyperbilirubinemia showed significantly higher scores on the positive and general psychiatric subscales of the PANSS (p < .0001) than patients without hyperbilirubinemia. CONCLUSION: The apparently higher frequency of Gilbert's syndrome in schizophrenic patients may reflect a relationship between hyperbilirubinemia and schizophrenic psychosis. Hypothetical explanations, such as a possible genetic disposition for Gilbert's syndrome, an increased vulnerability of red cell membranes, and the role of estrogens in schizophrenic patients, are discussed.

Reversible pitch perception deficit caused by carbamazepine.

Carbamazepine (CBZ) is an antiepileptic drug frequently used to treat a variety of neurologic diseases or symptoms. In addition, the drug is used as a mood stabilizer in patients with affective or schizophrenic disorders. Among its adverse effects, auditory disturbance is described rarely. In this report, we describe a 25-year-old woman who noted falsely higher pitch perception after starting CBZ treatment for schizoaffective disorder. We also review the literature reporting CBZ-associated abnormal pitch perception.

A case of small cerebral cyst and pericentric inversion of chromosome 9 that developed schizophrenia-like psychosis.

A case of schizophrenia-like psychosis (psychotic disorder not otherwise specified according to the DSM-IV criteria) with pericentric inversion on chromosome 9 [inv.(9) (p11; q13)] is reported. In this case, a minor brain anomaly, a small cyst in the left subcortex, was observed on magnetic resonance imaging of the brain. In the clinical course, prominent chronic hallucinations were observed; however, there was no evidence of the disorganization of personality, delusion, and deterioration in level of functioning that are usually seen in schizophrenia. This case and a review of the literature indicate that the pericentric region of chromosome 9 might be a potential areas of interest for the aetiology of psychiatric disorders. The phenotype-karyotype relationship of pericentric inversion on chromosome 9 and its relationship to psychosis are discussed.

A case of seizures 1 week after the cessation of interferon-alpha therapy.

We report on a 60-year-old woman with a history of bipolar mood disorder who had seizures and developed a delirious state 1 week after the cessation of interferon-alpha (IFN-alpha) for chronic hepatitis C. The IFN-alpha was administered to the patient for 7 weeks (266 million IU). One week after the cessation of IFN-alpha therapy, the patient had four generalized tonic-clonic seizures over a 2-day period and developed a delirious state for 2 months. We consider these seizures and delirious state to be related to IFN-alpha.

Nitric oxide-induced modification of glyceraldehyde-3-phosphate dehydrogenase with NAD+ is not ADP-ribosylation.

One biological effect of nitric oxide (NO) has been believed to be exerted through induction of the ADP-ribosyltransferase activity of glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Though this notion is based on the finding that NO increases the auto-ADP-ribosylation of GAPDH, controversial data have also been reported. To determine whether or not NO really activates ADP-ribosylation, we re-examined the NO-induced modification of GAPDH with NAD+. GAPDH was modified equally with [adenosine-14C]NAD+ and [carbonyl-14C]NAD+, indicating that the glycoside bond of NAD+ between ADP-ribose and nicotinamide is intact. The release of nicotinamide from NAD+ was not evident during incubation of GAPDH with [carbonyl-14C]NAD+. Thus, the modification of GAPDH is apparently not ADP-ribosylation. In addition, we found that basal and glyceraldehyde-3-phosphate-induced modifications of GAPDH, both of which have also been explained as ADP-ribosylation, were not ADP-ribosylation, and that the modification of GAPDH in the absence and presence of NO or GA3P was distinct in the dithiothreitol effect or resistance to HgCl2.