Type 1 versus Type 2 calreticulin mutations in essential thrombocythemia: A collaborative study of 1027 patients

CALR (calreticulin) trails JAK2 as the second most mutated gene in essential thrombocythemia (ET). Mutant CALR in ET is a result of frameshift mutations, caused by exon 9 deletions or insertions; type‐1, 52‐bp deletion (p.L367fs*46), and type‐2, 5‐bp TTGTC insertion (p.K385fs*47) variants constitute more than 80% of these mutations. The current study includes a total of 1027 patients divided into test (n = 402) and validation (n = 625) cohorts. Among the 402 ET patients in the test cohort, 227 (57%) harbored JAK2, 11 (3%) Myeloproliferative leukemia virus oncogene (MPL), and 114 (28%) CALR mutations; 12% were wild‐type for all three mutations (i.e., triple‐negative). Among the 114 patients with CALR mutations, 51 (45%) displayed type‐1 and 44 (39%) type‐2 variants; compared to mutant JAK2, both variants were associated with higher platelet and lower hemoglobin and leukocyte counts. However, male sex was associated with only type‐1 (P = 0.005) and younger age with type‐2 (P = 0.001) variants. Notably, platelet count was significantly higher in type‐2 vs. type‐1 CALR‐mutated patients (P = 0.03) and the particular observation was validated in the validation cohort that included 111 CALR‐mutated ET patients (P = 0.002). These findings, coupled with the recent demonstration of preferential expression of mutant and wild‐type CALR in megakaryocytes, suggest differential effects of CALR variants on thrombopoiesis. Am. J. Hematol. 89:E121–E124, 2014. © 2014 Wiley Periodicals, Inc.     

Invitro antibacterial activity of crude preparation of myrtle (Myrtus communis) on common human pathogens

BACKGROUND: Myrtle "Addus" (Myrtus communis) has long history as a traditional medicine/or different infectious disease by many peoples of the world and in Ethiopia too. OBJECTIVE: To asses the antibacterial activity of crude myrtle on some common human pathogens. METHODS: This experimental study was conducted in Jimma University from February to April 2004. The antimicrobial activity/ minimum inhibitory and minimum bactericidal concentrations/ of the crude preparation of Myrtle on E. coli, S. aureus, P. aeruginosa, P. vulgaris, P. mirabilis, K. aerogenes, S. typhi & S. shigie was determined using agar dilution methods. RESULTS: The Minimum Bactericidal Concentration of Myrtle for most tested microorganisms was similar to the Minimum Inhibitory Concentration. i.e. 0.5 mg/ml. for S. aureus, 2.5 mg/ml for P. mirabilis and P. vulgaris, 15 mg/ ml for Klebssiela and S. typhi, 20 mg/ml for P. aeruginosa. And the MBC of Myrtle for the two relatively least sensitive species, Shigella and E. coli was 40 mg/ml and 45 mg/ml of media, respectively. The antibacterial activity of Myrtle was markedly increased by 18 times after it has been autoclaved at 121 degrees C for 15 minutes. CONCLUSION: The preliminary study supports its traditional claim of effective anti-infective and could initiate further study that may ultimately facilitate to use myrtle as an antimicrobial agent. However, pharmacologically standardization and clinical evaluation on the effect of myrtle is essential, before using it as antibacterial agent in vivo.     

Extrahepatic portal hypertension: spleno-portal thrombosis secondary to protein C deficiency

Portal vein thrombosis (PVT) is the most frequent cause of hypertension portal extrahepatic. It is a rare disorder an the main risk factors are cirrhosis, hepatobiliary malignancies and prothrombotic disorders, which have been identified as major risk. Therapy with anticoagulants must to be considered in acute portal thrombosis or chronic one and proven hypercoagulability. We present the case of a twenty-nine years old patient, with extrahepatic portal hypertension secondary to portal and splenic vein thrombosis, who was diagnosed because of splenomegaly and a coagulation disorder. A protein C deficiency were discovered and anticoagulation and beta-blocker therapy were initiated. One year later the patient had not presented complications concerning to the disease or to the treatment.     

Angiogenic Factors and Angiogenesis Inhibitors in Exudative Pleural Effusions

The angiogenesis system has been implicated in inflammatory and neoplastic processes; nevertheless, it has been little studied in relation to the pleural space. Our aim is to analyze pleural and plasma levels of the activators-vascular endothelial growth factor, basic fibroblastic growth factor, and inhibitors-endostatin and thrombospondin-1 and to estimate the association between these factors and related biochemical markers. We analyzed pleural fluid from 105 patients with one of the following types of pleural effusion: empyema or complicated parapneumonic, non-complicated parapneumonic, tuberculous, neoplastic and transudative. Angiogenesis activators were higher in exudates than in transudates (p < 0.001) and in empyema than in non-complicated parapneumonic patients (p < 0.001). Endostatin showed no significant differences. Trombospondin-1 showed higher levels in exudates than in transudates and in empyema than in non-complicated parapneumonic effusions (p < 0.001). In pleural exudates there was a positive correlation of angiogenesis activators and trombospondin-1 with low glucose and pH and high LDH. There was no correlation between pleural and plasma levels of the angiogenesis factors. We conclude that exudative pleural effusions showed higher vascular endothelial growth factor, basic-fibroblastic growth factor and trombospondin-1 values than transudative effusions -that associated to low glucose and pH, and high LDH. There was no correlation between pleural and plasma concentrations, suggesting a compartmentalized response.Supported in part by FIS Grant 01/1408Presented in part at the International Conference of the American Thoracic Society, Seattle, 2003.     

Work ability and quality of life of brazilian industrial workers

The scope of this study was to evaluate the quality of life and work ability of industrial workers by means of self-perception questionnaires. 100 industrial production line workers on the night shift participated in this study. Authorized Brazilian translations of the Work Ability Index (WAI) and the Abbreviated World Health Organization Quality of Life (WHOQOL-Bref) Assessment Instrument were applied. The results show an association between work ability and the whole set of domains of quality of life, presenting a closer association with the physical domain (r =0.61). Furthermore, young men obtained higher ability to work results, while women aged between 30 and 39 had the lowest quality of life indices (p =0.027), especially in the Social Relationships and Environment domains. This shows that preventive guidelines for the improvement of aspects linked to the Physical domain are necessary both in the workplace and outside the workplace, since this interaction exacerbates the effects on the physical aspect in both spheres.     

Laser induced breakdown spectroscopy for bone and cartilage differentiation - ex vivo study as a prospect for a laser surgery feedback mechanism

Laser surgery enables for very accurate, fast and clean modeling of tissue. The specific and controlled cutting and ablation of tissue, however, remains a central challenge in the field of clinical laser applications. The lack of information on what kind of tissue is being ablated at the bottom of the cut may lead to iatrogenic damage of structures that were meant to be preserved. One such example is the shaping or removal of diseased cartilaginous and bone tissue in the temporomandibular joint (TMJ). Diseases of the TMJ can induce deformation and perforation of the cartilaginous discus articularis, as well as alterations to the cartilaginous surface of the condyle or even the bone itself. This may result in restrictions of movement and pain. The aim of a surgical intervention ranges from specific ablation and shaping of diseased cartilage, bone or synovial tissues to extensive removal of TMJ structures. One approach to differentiate between these tissues is to use Laser Induced Breakdown Spectroscopy (LIBS). The ultimate goal is a LIBS guided feedback control system for surgical laser systems that enables real-time tissue identification for tissue specific ablation. In the presented study, the authors focused on the LIBS based differentiation between cartilage tissue and cortical bone tissue using an ex-vivo pig model.OCIS codes: (170.1020) Ablation of tissue, (170.1470) Blood or tissue constituent monitoring, (170.6935) Tissue characterization, (300.6365) Spectroscopy, laser induced breakdown     

Seroepidemiological and socioeconomic studies of genital chlamydial infection in Ethiopian women.

OBJECTIVE--To measure the prevalence of chlamydial genital infection in Ethiopian women attending gynaecological, obstetric and family planning clinics; to identify the epidemiological, social and economic factors affecting the prevalence of infection in a country where routine laboratory culture and serological tests for chlamydial species are unavailable; to determine the risk factors for genital chlamydial infection in those with serological evidence of other sexually transmitted diseases. SUBJECTS--1846 Ethiopian women, outpatient attenders at two teaching hospitals and a mother and child health centre in Addis Ababa, Ethiopia. SETTING--Gynaecological outpatient department, antenatal, postnatal and family planning clinics. METHODS--Sera were tested for type-specific anti-chlamydial antibodies using purified chlamydial antigens (C. trachomatis A-C (CTA-C), C. trachomatis D-K (CTD-K), Lymphogranuloma venereum (LGV1-3), and C. pneumoniae (CPn)), in a micro-immunofluorescence test. The genital chlamydia seropositivity was analysed against patient's age, clinic attended, ethnic group, religion, origin of residence, age at first marriage and first coitus, income, number of sexual partners, duration of sexual activity, marital status/profession, obstetric and contraceptive history, and seropositivity for other sexually transmitted diseases. RESULTS--Overall exposure to chlamydia species was found in 84%, genital chlamydial infection in 62%, and titres suggestive of recent or present genital infection in 42% of those studied. Genital chlamydial infection was highest (64%) in family planning and lowest (54%) in antenatal clinic attenders. Exposure to genital chlamydia species was influenced by ethnic group and religion. Those married and sexually active under 13 years of age had greater exposure (69%) to genital chlamydial infection than those first sexually active aged over 18 (46%). Prevalence of infection was highest in those with more than five sexual partners (78%) and in bargirls (84%). The lowest income groups had a higher prevalence (65%) of genital chlamydial infection than the wealthiest (48%). Multivariate analysis showed the most important factors to be age at first coitus, religion, prostitution and present age of the woman in that order. Risk for genital chlamydial infection was increased in those with seropositivity for syphilis, gonorrhoea, HSV-2 but not HBV infection. CONCLUSION/APPLICATION--Chlamydial genital infections are highly prevalent in both symptomatic and asymptomatic Ethiopian women. The high prevalence of infection reported reflects a complexity of socioeconomic factors: very early age at first marriage and first coitus, instability of first marriage, subsequent divorce and remarriage or drift into prostitution, all of which are influenced by ethnic group, religion and poverty--together with transmission from an infected group of prostitutes by promiscuous males to their wives, lack of diagnostic facilities and inadequate treatment of both symptomatic and asymptomatic men and women. The problem of chlamydial disease in Ethiopia needs to be addressed urgently in the context of control of STD.     

Delayed initiation of adjuvant chemotherapy among women with breast cancer in Addis Ababa,Ethiopia

Breast Cancer Research and Treatment - Chemotherapy within 90&nbsp;days following surgery for non-metastatic breast cancer is the standard of care. There are no data, however, on the extent of...     

Four superoxide dismutases contribute to Bacillus anthracis virulence and provide spores with redundant protection from oxidative stress

The Bacillus anthracis genome encodes four superoxide dismutases (SODs), enzymes capable of detoxifying oxygen radicals. That two of these SODs, SOD15 and SODA1, are present in the outermost layers of the B. anthracis spore is indicated by previous proteomic analyses of the exosporium. Given the requirement that spores must survive interactions with reactive oxygen species generated by cells such as macrophages during infection, we hypothesized that SOD15 and SODA1 protect the spore from oxidative stress and contribute to the pathogenicity of B. anthracis. To test these theories, we constructed a double-knockout (Delta sod15 Delta sodA1) mutant of B. anthracis Sterne strain 34F2 and assessed its lethality in an A/J mouse intranasal infection model. The 50% lethal dose of the Delta sod15 Delta sodA1 strain was similar to that of the wild type (34F2), but surprisingly, measurable whole-spore SOD activity was greater than that in 34F2. A quadruple-knockout strain (Delta sod15 Delta sodA1 Delta sodC Delta sodA2) was then generated, and as anticipated, spore-associated SOD activity was diminished. Moreover, the quadruple-knockout strain, compared to the wild type, was attenuated more than 40-fold upon intranasal challenge of mice. Spore resistance to exogenously generated oxidative stress and to macrophage-mediated killing correlated with virulence in A/J mice. Allelic exchange that restored sod15 and sodA1 to their wild-type state restored wild-type characteristics. We conclude that SOD molecules within the spore afford B. anthracis protection against oxidative stress and enhance the pathogenicity of B. anthracis in the lung. We also surmise that the presence of four SOD alleles within the genome provides functional redundancy for this key enzyme.