Aquagenic pruritus in polycythemia vera: Characteristics and influence on quality of life in 441 patients

Aquagenic pruritus (AP) is a symptom typical for polycythemia vera, but very little is known about its exact frequency, characteristics, influence on quality of life, and proper treatment. Therefore, we investigated these aspects in a large cohort of German patients with polycythemia vera using a patient directed questionnaire. Our analysis revealed that 301 of 441 analyzed patients suffered from AP. In 64.8%, AP occurred on average 2.9 years prior to diagnosis of polycythemia vera. Only in 15.4% did this lead to a hematological investigation. AP occurs primarily on the trunk and proximal parts of the extremities. Most patients complain about itching (71.8%), the remainder about tickling, stinging, or burning sensations. Forty‐four patients (14.6%) classified the pruritus as “unbearable.” Patients with AP reported reduced global health status and higher fatigue, pain, and dyspnea. Only 24% of patients received pruritus specific treatment for pruritus consisting mostly of histamine antagonists, which ameliorated symptoms in about half of the patients. In 5.6% of patients, polycythemia vera directed therapy (phlebotomy/cytoreduction) resolved the symptoms. In summary, AP is a serious symptom in patients with polycythemia vera, which until recently was difficult to treat. The advent of the novel JAK2 inhibitors, however, may open new ways for therapy. Am. J. Hematol. 88:665–669, 2013. © 2013 Wiley Periodicals, Inc.     

Basal and residual lower esophageal pressures increase in old age in classic achalasia,but not vigorous achalasia

Background and Aim: The relationship between age and esophageal motility parameters (i.e. basal and residual pressure of the lower esophageal sphincter [LES]) remains to be established in achalasia patients, possibly because most previous studies did not distinguish between classic and vigorous achalasia patients. We investigated the relationship between age and esophageal motility parameters in both classic and vigorous achalasia patients. Methods: A retrospective review of esophageal manometry data in a single center was undertaken. Basal and residual pressure for LES was analyzed. A total of 103 achalasia patients were enrolled, comprising 84 classic and 19 vigorous types. They were subdivided into three different age groups as follows: 21–40 years old (group A), 41–60 years old (group B), and over 60 years old (group C). Results: In classic achalasia patients (M : F = 27:57, mean age = 44 ± 15 years old) the older age group showed a significantly higher basal LES pressure (49.62 ± 19.63 mmHg) than the younger age group (P < 0.0001). Moreover, the older age group also showed significantly high residual LES pressure (20.46 ± 8.61 mmHg) than the younger age group (P = 0.0006). In contrast, in vigorous achalasia patients (M : F = 12:7, mean age: 47 ± 15 years old) there were no difference between age and motility indices (all P > 0.05). Conclusion: In classic achalasia patients there appears to be a correlation between age and esophageal motility indices, especially basal and residual LES pressure. Such correlations do not appear to exist for vigorous achalasia patients.     

11Beta-hydroxysteroid dehydrogenase inhibition improves cognitive function in healthy elderly men and type 2 diabetics

In aging humans and rodents, inter-individual differences in cognitive function have been ascribed to variations in long-term glucocorticoid exposure. 11beta-Hydroxysteroid dehydrogenase type 1 (11beta-HSD1) regenerates the active glucocorticoid cortisol from circulating inert cortisone, thus amplifying intracellular glucocorticoid levels in some tissues. We show that 11beta-HSD1, but not 11beta-HSD2, mRNA is expressed in the human hippocampus, frontal cortex, and cerebellum. In two randomized, double-blind, placebo-controlled crossover studies, administration of the 11beta-HSD inhibitor carbenoxolone (100 mg three times per day) improved verbal fluency (P < 0.01) after 4 weeks in 10 healthy elderly men (aged 55-75 y) and improved verbal memory (P < 0.01) after 6 weeks in 12 patients with type 2 diabetes (52-70 y). Although carbenoxolone has been reported to enhance hepatic insulin sensitivity in short-term studies, there were no changes in glycemic control or serum lipid profile, nor was plasma cortisol altered. 11beta-HSD1 inhibition may be a new approach to prevent/ameliorate cognitive decline.     

Effect of Intra-Coronary Nicorandil Administration Prior to Reperfusion in Acute ST Segment Elevation Myocardial Infarction

Background Intravenous nicorandil infusion with percutaneous coronary intervention (PCI) has been reported to reduce reperfusion injury events and improve cardiac function in patients with acute myocardial infarction (MI). However, there is limited information on the use of intracoronary nicorandil. Methods and Results In the present study, 73 patients with acute ST segment elevation MI undergoing PCI were randomly assigned to the Nicorandil Group (n=37) or the Control Group (n=36). The composite endpoints were the incidences of ventricular arrhythmia, no-reflow and slow flow. A significant difference in the composite endpoint was observed in the Nicorandil Group when compared with the Control Group (p=0.037). The occurrence of post Thrombolysis In Myocardial Infarction (TIMI) grade 3 was significantly higher in the Nicorandil Group (p=0.019). Major adverse cardiac events during hospitalization and within 30 days of treatment were similar between the 2 groups. Conclusion Administration of intracoronary nicorandil reduced the occurrence of no-reflow, slow reflow, and reperfusion arrhythmia, and improved the myocardial perfusion grade, TIMI flow during PCI and improved clinical outcomes in patients with acute MI. (Circ J 2008; 72: 1425 - 1429).     

The adrenal secretory serine protease AsP is a short secretory isoform of the transmembrane airway trypsin-like protease

To further elucidate the role of proteases capable of cleaving N-terminal proopiomelanocortin (N-POMC)-derived peptides, we have cloned two cDNAs encoding isoforms of the airway trypsin-like protease (AT) from mouse (MAT) and rat (RAT), respectively. The open reading frames comprise 417 amino acids (aa) and 279 aa. The mouse AT gene was located at chromosome 5E1 and contains 10 exons. The longer isoform, which we designated MAT1 and RAT1, has a simple type II transmembrane protein structure, consisting of a short cytoplasmic domain, a transmembrane domain, a SEA (63-kDa sea urchin sperm protein, enteropeptidase, agrin) module, and a serine protease domain. The human homolog of MAT1 and RAT1 is the human AT (HAT). The shorter isoform, designated MAT2 and RAT2, which contains an alternative N terminus, was formerly described in the rat as adrenal secretory serine protease (AsP) and has been shown to be involved in the processing of N-POMC-derived peptides. In contrast to the long isoform, neither MAT2 and RAT2 (AsP) contain a transmembrane domain nor a SEA domain but an N-terminal signal peptide to direct the enzyme to the secretory pathway. The C terminus, covering the catalytic triad, is identical in both isoforms. Immunohistochemically, MAT/RAT was predominantly expressed in tissues of the upper gastrointestinal and the respiratory tract-but also in the adrenal gland. Moreover, isoform-specific RT-PCR and quantitative PCR analysis revealed a complex expression pattern of the two isoforms with differences between mice and rats. These findings indicate a multifunctional role of these proteases beyond adrenal proliferation.     

Survey of implementation of the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines in nine Asian countries

After the release of the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines in 2001 and update in 2003, its implementation in nine Asian countries was investigated. Questionnaire surveys involving thoraco-pulmonary physicians or internists investigated the awareness and consensus of the GOLD guidelines including the care and management of chronic obstructive pulmonary disease (COPD) patients in Asian. Two surveys were conducted, in June 2002 and March 2004, through questionnaires by direct mail in Japan and face-to-face interviews in the other countries. Approximately 600 questionnaires were returned with approximately 84% awareness of the publication and its update and nearly 90% appreciated the globalization efforts. The survey revealed great variances concerning the definition of COPD, its diagnosis, and use of computed tomography. As for the implementation, the majority answered the use of the combined local and GOLD guidelines in five of nine countries surveyed, while the GOLD guidelines were implemented mainly in Korea, suggesting the influence in daily practice for care and management of COPD patients. Implication of rehabilitation in clinical practice has not been standardized despite high evidence of its advantages. Most respondents stated the necessity of developing a local or regional guideline for best practice. Our survey revealed: (i) awareness of the GOLD guidelines was high and well accepted; (ii) the possibility of developing a uniform or standard guideline in Asia is low due to local characteristics; (iii) modifications of the GOLD guidelines may be more practical; and (iv) that the multidisciplinary pulmonary rehabilitation program needs to be further activated in GOLD implementation for the Asia–Pacific region.