PDE4B polymorphisms and decreased PDE4B expression are associated with schizophrenia

Schizophrenia has a complex genetic underpinning and variations in a number of candidate genes have been identified that confer risk of developing the disorder. We report in the present studies that several single nucleotide polymorphisms (SNPs) and a two-SNP haplotype in PDE4B are associated with an increased incidence of schizophrenia in two large populations of Caucasian and African American patients. The SNPs in PDE4B associated with schizophrenia occur in intronic sequences in the vicinity of a critical splice junction that gives rise to the expression of PDE4B isoforms with distinct regulation and function. We also observed specific decreases in phosphodiesterase 4B (PDE4B) isoforms in brain tissue obtained postmortem from patients diagnosed with schizophrenia and bipolar disorder. PDE4B metabolically inactivates the second messenger cAMP to regulate intracellular signaling in neurons throughout the brain. Thus, the present observations suggest that dysregulation of intracellular signaling mediated by PDE4B is a significant factor in the cause and expression, respectively, of schizophrenia and bipolar disorder and that targeting PDE4B-regulated signaling pathways may yield new therapies to treat the totality of these disorders.     

Multimedia educational aids for improving consumer knowledge about illness management and treatment decisions: a review of randomized controlled trials

Psychiatric practice is becoming increasingly more complex in terms of the available treatment options, use of new technologies for assessments, and a need for psychiatric patients and their caregivers to be familiar with general medical procedures. This trend will only intensify in the years to come. Routine methods of providing information relevant to clinical decision making about healthcare evaluations or management are often suboptimal. Relatively little research has been done on enhancing the capacity of psychiatric patients and the caregivers to make truly informed decisions about management. In this paper, we review studies that compared the effects of multimedia (video- or computer-based) educational aids with those of routine procedures to inform healthcare consumers about medical evaluations or management. Although most of these investigations were conducted in non-psychiatric patients, the results should be relevant for psychiatric practice of tomorrow. We searched MEDLINE, PsycINFO, and CINAHL bibliographic databases. Randomized controlled trials that used objective measures of knowledge or understanding of the information provided were selected. Studies were rated as positive if the multimedia educational aid resulted in a greater improvement in knowledge or understanding than the control condition. The quality of each study was also rated using a newly developed Scale for Assessing Scientific Quality of Investigations (SASQI). A total of 37 randomized controlled trials were identified. Nearly two-thirds of the studies (23/37) in diverse patient populations and for varied medical assessments and treatments reported that multimedia educational aids produced better understanding of information compared to routine methods. SASQI scores for the positive and negative studies were comparable, suggesting that lower quality was not related to positive findings. In conclusion, multimedia educational aids hold promise for improving the provision of complex medical information to patients and caregivers. It is likely that as psychiatric patients and their treating clinicians face increasingly complex choices regarding mental health treatment, multimedia decisional aids could become an effective supplement to the clinician patient interaction in near future.     

Treatment of refractory adult‐onset pityriasis rubra pilaris with TNF‐alpha antagonists: a case series

Background Pityriasis rubra pilaris (PRP) is a rare inflammatory dermatosis with frequent clinical presentation as erythroderma. Conventional systemic treatment is often unsatisfactory and limited by long‐term toxicity. The use of tumour necrosis factor (TNF) antagonists has been reported previously in single cases, but lacking long‐term follow‐up or comparison between different biological agents. Objectives To assess the long‐term efficacy and safety of TNF‐alpha antagonist, infliximab and etanercept, either in monotherapy or in combination therapy of severe, refractory adult‐onset PRP. Methods Seven patients of adult‐onset PRP, six newly diagnosed type‐I and 1 type‐II, which were resistant or ineligible to conventional systemic treatment, received a single course of infliximab or etanercept therapy, alone or in combination with low‐dose acitretin (>0.25 mg/kg/daily). After complete remission and treatment discontinuation, a follow‐up period of 12 months was evaluated for relapses. Results Six patients obtained complete remission after a single course of anti‐TNF‐alpha therapy: mean therapy duration was 19.3 weeks (range 6–48 weeks). All patients obtained significant clearing (>75% of body surface area) of skin lesions at week 12. Two patients with marked keratoderma developed localized disease recurrence during treatment. During follow‐up, only a single patient, affected by type II PRP, had disease relapse. Conclusions Both TNF‐alpha antagonists proved successful for the treatment of refractory, adult‐onset PRP, yielding complete and persistent clinical responses in type‐I PRP. Infliximab was associated with a more rapid onset of action, while treatment duration was comparable with etanercept. PRP type II warranted long‐term therapy and showed relapse after drug discontinuation.     

IDEAL PAIN RELIEF FOLLOWING LAPAROSCOPIC CHOLECYSTECTOMY

In a previous report the effectiveness of intraperitoneal bupivacaine in reducing pain following laparoscopic cholecystectomy was demonstrated. Other methods of pain relief are commonly used but none has been compared following laparoscopic cholecystectomy. In two further studies we have compared the analgesic effect of intraperitoneal bupivacaine against wound infiltration with bupivacaine, and against intraperitoneal bupivacaine with the addition of a non-steroidal anti-inflammatory drug (NSAID) in patients undergoing laparoscopic cholecystectomy. Two consecutive studies were performed. In the first, patients in group 1 were given 20 ml of 0.25% bupivacaine into the peritoneal cavity; patients in group 2 were given 20 ml of 0.25% bupivacaine injected into the trocar wounds. In the second study, patients in group 1 were given 20 ml of 0.25% bupivacaine into the peritoneal cavity; patients in group 2 were given 20 ml of 0.25% bupivacaine into the peritoneal cavity and a diclofenac suppository (100 mg) one hour before surgery. Postoperative pain was assessed with a visual analogue pain scale. There was no difference in pain scores in the two groups in either study. Intraperitoneal bupivacaine is as effective as wound infiltration. The addition of an NSAID makes no difference in the reduction of postoperative pain following laparoscopic cholecystectomy.     

Human auditory brainstem response to temporal gaps in noise.

Gap detection is a commonly used measure of temporal resolution, although the mechanisms underlying gap detection are not well understood. To the extent that gap detection depends on processes within, or peripheral to, the auditory brainstem, one would predict that a measure of gap threshold based on the auditory brainstem response (ABR) would be similar to the psychophysical gap detection threshold. Three experiments were performed to examine the relationship between ABR gap threshold and gap detection. Thresholds for gaps in a broadband noise were measured in young adults with normal hearing, using both psychophysical techniques and electrophysiological techniques that use the ABR. The mean gap thresholds obtained with the two methods were very similar, although ABR gap thresholds tended to be lower than psychophysical gap thresholds. There was a modest correlation between psychophysical and ABR gap thresholds across participants. ABR and psychophysical thresholds for noise masked by temporally continuous, high-pass, or spectrally notched noise were measured in adults with normal hearing. Restricting the frequency range with masking led to poorer gap thresholds on both measures. High-pass maskers affected the ABR and psychophysical gap thresholds similarly. Notched-noise-masked ABR and psychophysical gap thresholds were very similar except that low-frequency, notched-noise-masked ABR gap threshold was much poorer at low levels. The ABR gap threshold was more sensitive to changes in signal-to-masker ratio than was the psychophysical gap detection threshold. ABR and psychophysical thresholds for gaps in broadband noise were measured in listeners with sensorineural hearing loss and in infants. On average, both ABR gap thresholds and psychophysical gap detection thresholds of listeners with hearing loss were worse than those of listeners with normal hearing, although individual differences were observed. Psychophysical gap detection thresholds of 3- and 6-month-old infants were an order of magnitude worse than those of adults with normal hearing, as previously reported; however, ABR gap thresholds of 3-month-old infants were no different from those of adults with normal hearing. These results suggest that ABR gap thresholds and psychophysical gap detection depend on at least some of the same mechanisms within the auditory system.     

Immunoassay method validation for a modified EMIT phencyclidine assay.

Immunoassay drug testing methods, that have been modified from the manufacturers' recommended procedure to be used for the analysis of federally regulated specimens or other forensic samples require evaluation to ensure their scientific validity. These validation studies must demonstrate the accuracy, precision, and linearity of the modified immunoassay around the cutoff concentration, substantiate adequate rate separation, and verify the ability of the assay to differentiate positive and negative samples. Modification of the EMIT d.a.u. phencyclidine assay in order to achieve the federally mandated cutoff concentration of 25 ng/mL is common. This study describes the validation of a modified EMIT phencyclidine assay and a protocol that allows for the evaluation of similarly modified immunoassays.