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.     

Effects of dietary composition on life span of Drosophila buzzatii and its short-lived sibling species D. koepferae

Two sibling Drosophila species dramatically divergent in longevity, Drosophila buzzatii and D. koepferae, were examined for possible effects of both developmental culture medium and dietary composition (DC) on longevity. Longevity was greatly increased in the longer lived D. buzzatii when flies were reared and fed on a rich-in-nutrient and cactus-based culture (R-CBC) as compared to longevity in a poor nutrient culture (PNC). In D. buzzatii, life span was further increased by exposing flies to short periods of a poor-in-nutrient and cactus-based culture (P-CBC). In contrast, variation in the here used nutrient composition did not change life span in the shorter lived D. koepferae, as longevity in this species did not differ among R-CBC, P-CBC and PNC cultures. Hormesis is a plausible explanation for the beneficial biological effects against aging arising from brief exposure to a lowed calorie food source in D. buzzatii. This study shows that genetic variation between closely related species is substantial for dietary effects on longevity.     

Impact of cardiovascular risk factors on vessel wall inflammation and calcified plaque burden differs across vascular beds: a PET-CT study

To evaluate the effect of age, gender and cardiovascular risk factors on vessel wall inflammation and the calcified plaque burden in different vascular beds as assessed by PET/CT. 315 patients (mean age: 57.8 years, 123 male and 192 female) who underwent whole body 18F-FDG PET/CT examinations were included in the study. Blood pool-corrected standardised uptake value (TBR) and the calcified plaque score (CPS, grade 0–4) were determined in the thoracic and abdominal aorta, both common carotid and both iliac arteries. The following cardiovascular risk factors were documented: Age ≥65 years (n = 114), male gender (n = 123), diabetes (n = 15), hyperlipidemia (n = 62), hypertension (n = 76), body mass index (BMI) ≥ 30 (n = 38), current smoker (n = 32). Effects of risk factors on TBR and CPS in different arterial beds were assessed using multivariate regression analysis. In the thoracic aorta TBR was independently associated with age ≥65 years and male gender, CPS was independently associated with age ≥65 years, male gender, hypertension and diabetes. In the abdominal aorta, TBR was independently associated with age ≥65 years and male gender, CPS with age ≥65 years, diabetes and smoking. Independent associations in the carotid arteries were found for age ≥65 years, male gender and BMI ≥ 30 in TBR and for age ≥65 and diabetes in CPS. In the iliac arteries, TBR was independently associated with age ≥65 and CPS with age ≥65, male gender, hypertension, diabetes and smoking. Findings of this PET/CT study demonstrate that the impact of cardiovascular risk factors on vessel wall inflammation and calcified plaque burden differs across vascular territories. Overall, CPS was more closely associated with cardiovascular risk factors compared to TBR.     

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.     

Adherence to evidence-based statin guidelines reduces the risk of hospitalizations for acute myocardial infarction by 40%: a cohort study.

AIMS: To investigate the 'real world' effectiveness of robust statin therapy, focusing on the effect of dose and early treatment discontinuation on the risk of hospitalization for acute myocardial infarction (AMI). METHODS AND RESULTS: In the PHARMO database, including among others drug-dispensing and hospital discharge records for more than two million subjects in the Netherlands, 59,094 new users of statins in the period 1 January 1991 until 31 December 2004, >or=18 years of age were identified. In these patients, exposure to statins, both in terms of persistence and dose, was determined over the first two treatment years. To determine the risk for AMI, patients were followed from this 2-year time point until the first hospital admission for AMI, death, or end of the study period. A total of 31,557 patients (53%) discontinued statin use within 2 years; 20 883 patients (35%) were persistent users with an average equipotent dose>or=4. A 30% reduction in risk of hospitalization for AMI with persistent statin use was observed. The protective effect increased with a higher dose (20 and 40% risk reduction with an equipotent doseor=4, respectively). CONCLUSION: These results show that statins are suboptimally used in real life for having the maximum benefit in terms of preventing AMI.