Utility of the Dermatology Life Quality Index at initiation or switching of biologics in real-life Japanese patients with plaque psoriasis: Results from the ProLOGUE study

BackgroundPlaque psoriasis significantly affects patients’ health-related quality of life. To aid treatment decisions, not only objective assessment by physicians but also subjective assessment by patients is important.ObjectiveTo assess the significance of Dermatology Life Quality Index (DLQI) evaluation at the time of biologics introduction in clinical practice in Japanese patients with plaque psoriasis.MethodsThis was a single-arm, open-label, multicenter study. At baseline, Psoriasis Area and Severity Index (PASI) and DLQI scores were measured and stratified based on DLQI scores ≥6/≤5 and PASI scores ≤10/>10. Other patient-reported outcomes assessed included EQ-5D-5L, itch numerical rating scale (NRS), skin pain NRS, Generalized Anxiety Disorder-7 (GAD-7), Patient Health Questionnaire-8 (PHQ-8), Sleep Problem Index-II (SPI-II), and Treatment Satisfaction Questionnaire for Medication-9 (TSQM-9).ResultsOf the 73 enrolled patients, 23 had PASI scores ≤10. Those with PASI/DLQI scores >10/≥6 had a significantly higher median PASI score than those with PASI/DLQI scores >10/≤5 (p = 0.0125). Regardless of PASI scores (>10/≤10), median itch NRS and GAD-7 scores were significantly higher in patients with DLQI scores ≥6 than in those with DLQI scores ≤5 (itch NRS, p = 0.0361 and p = 0.0086, respectively; GAD-7, p = 0.0167 and p = 0.0273, respectively). Patients with PASI/DLQI scores ≤10/≥6 had significantly higher skin pain NRS (p = 0.0292) and PHQ-8 (p = 0.0255) scores and significantly lower median SPI-II scores (p = 0.0137) and TSQM-9 Effectiveness domain scores (p = 0.0178) than those with PASI/DLQI scores ≤10/≤5.ConclusionDLQI may be useful for assessing patients’ concerns that cannot be identified by PASI alone while initiating biologics or switching from other biologics in clinical practice.     

Adenocarcinoma Arising in the Retrorectal Space: Report of a Case

(Received for publication on June 27, 1996; accepted on Mar. 4, 1997)     

Application of Ultra Short Acting Beta Blockade (Esmolol) in Pediatric Open Heart Surgery: A Trial in Total Anomalous Pulmonary Venous Return

A bstract Background : In the repair of total anomalous pulmonary venous return (TAPVR) under cardiopulmonary bypass, esmolol, ultra short acting beta blocker, was applied to obtain low heart rate and weak ventricular contraction under mild hypothermic cardiopulmonary bypass. Methods : Five infants aged from 14 to 158 days with an average of 70 days, underwent a primary or palliative repair of TAPVR. The type of anomalous return was supracardiac type (2), infracardiac (2), and intracardiac (1). A primary repair was done in three for isolated TAPVR with bypass time of 65 to 76 minutes, and a palliative repair for two with complex anomalies with bypass time of 64 and 87 minutes. Results : There was one operative death from cerebral bleeding in an infant with complex TAPVR who underwent simultaneous pulmonary banding. Conclusion : This strategy seems to be applicable in pediatric cardiac surgery when aortic cross-clamping is better to be avoided and the surgery is mainly limited to the atrial level.     

Cyclooxygenase‐2 Expression and Prostaglandin E2 Production in Response to Acidic pH Through OGR1 in a Human Osteoblastic Cell Line

Acidosis has been shown to induce depletion of bone calcium from the body. This calcium release process is thought to be partially cell mediated. In an organ culture of bone, acidic pH has been shown to induce cyclooxygenase‐2 (COX‐2) induction and prostaglandin E₂ (PGE₂) production, resulting in stimulation of bone calcium release. However, the molecular mechanisms whereby osteoblasts sense acidic circumstances and thereby induce COX‐2 induction and PGE₂ production remain unknown. In this study, we used a human osteoblastic cell line (NHOst) to characterize cellular activities, including inositol phosphate production, intracellular Ca²⁺ concentration ([Ca²⁺]_i), PGE₂ production, and COX‐2 mRNA and protein expression, in response to extracellular acidification. Small interfering RNA (siRNA) specific to the OGR1 receptor and specific inhibitors for intracellular signaling pathways were used to characterize acidification‐induced cellular activities. We found that extracellular acidic pH induced a transient increase in [Ca²⁺]_i and inositol phosphate production in the cells. Acidification also induced COX‐2 induction, resulting in PGE₂ production. These proton‐induced actions were markedly inhibited by siRNA targeted for the OGR1 receptor and the inhibitors for G_q/11 protein, phospholipase C, and protein kinase C. We conclude that the OGR1/G_q/11/phospholipase C/protein kinase C pathway regulates osteoblastic COX‐2 induction and subsequent PGE₂ production in response to acidic circumstances.     

Dimethylsphingosine regulates intracellular pH and Ca(2+) in human monocytes

Dimethylsphingosine (DMS) was first reported as an inhibitor of protein kinase C and later has been used as a specific inhibitor of sphingosine kinase. Furthermore, its anti-cancer effect has become a basis for development of chemotherapy. Nevertheless, its anti-neoplastic mechanism has poorly been understood. In the present study, we observed that DMS increased intracellular pH and Ca(2+) concentration in U937 human monocytes. To further characterize these DMS-induced actions, we employed structurally-related sphingolipids and specific pharmacological tools such as inhibitors of protein kinase C and Na(+)/H(+) exchanger and found that the two responses of DMS were mimicked by four stereoisomers of sphingosine and two isomers to dihydrosphingosine, but not with sphingosine 1-phosphate, sphingosyl-phosphorylcholine, and C2-ceramide. Furthermore, DMS-induced pH increase was independent of Na(+)/H(+) exchanger activity. We also characterized the interrelationship between DMS-induced pH increase and DMS-induced Ca(2+) increase. Since DMS is considered to be a good anti-cancer candidate, our characterization of DMS actions provides useful information for development of DMS chemotherapy.     

Synchronous invasive squamous cell carcinoma and clear cell adenocarcinoma of the uterine cervix: a different human papillomavirus status

BACKGROUND: A multiple primary invasive carcinoma of the cervix is a rare condition and is seldom composed of squamous cell carcinoma and clear cell adenocarcinoma. CASE: A 47-year-old woman presented with contact bleeding. The anterior lip of the cervix revealed a 2.0-cm protruded mass. Preoperative pathological and imaging studies demonstrated the squamous cell carcinoma of the exocervix alone. Radical hysterectomy was performed on the diagnosis of stage 1B cervical cancer. Histological examination of the specimen manifested a coexisting invasive clear cell adenocarcinoma in the endocervix. Human papillomavirus (HPV) 18 was detected in the squamous cell carcinoma; however, no HPV was detected in the clear cell adenocarcinoma. CONCLUSION: This finding suggests that there was an obvious difference in association of HPV with the two neoplasms.     

Management for neonatal aspiration syndrome caused by vernix caseosa

OBJECTIVE: To clarify resuscitation methods against the lethal vernix caseosa aspiration syndrome. METHOD: A single case report with a literature review. RESULTS: Our case report was associated with aspiration syndrome caused by an airway obstruction of vernix caseosa: a proteolipid biofilm synthesized by the fetus. A 23-year-old woman normally delivered a mature infant at term. The infantile oral cavity was filled with numerous aggregates of vernix caseosa. Two hours after his birth, the infant died from respiratory insufficiency. We discuss the difference between management of our case and the previously reported case. CONCLUSION: Pregnant women with a diffuse pattern of high-level echoes in prenatal ultrasonography, suggesting the presence of massive vernix caseosa, should be transferred to a well-equipped institution that can administer inhaled nitric oxide and extracorporeal membrane oxygenation.