Dengue in Grenada.

OBJECTIVES: Dengue fever is endemic in the country of Grenada and is grossly underreported as a source of morbidity. The goal of this study was to assess the status of dengue fever in a representative community in Grenada. METHODS: Surveys were conducted in the Mont Tout/Grand Anse Valley area in the parish of St. George's from March to June 1996. The objectives of the survey were to: (1) to assess the knowledge, attitudes, and practices (KAP) of residents; (2) to determine the presence of larval and adult Aedes aegypti and their potential breeding sites; and (3) to identify the seroprevalence of specific immunoglobulin G (IgG) dengue antibodies in the local population. RESULTS: Out of the 102 respondents to the KAP survey, 100 of them (98%) reported never having had dengue fever. Of the 75 persons who agreed to have blood samples taken, 70 of them (93%) (95% confidence interval = 85.1%-97.8%) tested positive with the IgG enzyme-linked immunosorbent assay, indicating past exposure. In terms of water storage, 98 of 102 respondents (96%) stored fresh water in containers. The vector survey found 57 of the 102 households (56%) had Ae. aegypti larvae in water containers on their property, and 94 of 102 dwellings (92%) had adult Ae. aegypti mosquitoes indoors. CONCLUSIONS: Although many people were familiar with dengue fever and mosquitoes, the 1996 survey found that their knowledge of the important relationships among mosquitoes, human behavior, and disease transmission was incomplete. Since 1996, continued education efforts have been made in the public school system and with national public health campaigns, yet little effort has been specifically targeted towards our study community. These data suggest Grenada has a need for continued community education that addresses dengue fever transmission and Ae. aegypti reduction.     

Guideline chaos: conflicting recommendations for preoperative cardiac assessment

The American College of Cardiology/American Heart Association (ACC/AHA) and the American College of Physicians (ACP) have disseminated guidelines to assess preoperative cardiac risks before noncardiac surgery. The objectives of this study were to determine if these guidelines differ in preoperative recommendations for a group of patients, and whether these recommendations differ from actual provider recommendations. In this retrospective cohort study, patient characteristics and physician recommendations were abstracted from electronic medical records of consecutive patients attending a Veteran Affairs medical preoperative evaluation clinic from January 1 to April 1, 1998. Patient characteristics were used to determine what preoperative cardiac testing should have been ordered if each guideline was followed. Possible recommendations included operation without testing (OWT), noninvasive stress testing (NST), cardiac catheterization (CC), or cancel or delay surgery (OTHER). Recommendations were compared using statistical tests for agreement. Of the 138 patients identified, most underwent moderate-risk surgeries. Recommendations for preoperative testing were discordant between guidelines for 17% of patients (kappa = 0.38). Guidelines never agreed on the need for NST. Extreme differences in recommendations (i.e., one recommends OWT, the other CC) occurred in 9 patients (7%). Physicians ordered NST more often (n = 27) than either guideline. In this subgroup of patients where providers ordered a NST, the 2 guidelines significantly differed (kappa = 0.26). When applied to real patients being evaluated for surgery, ACC/AHA and ACP guidelines significantly differed in recommendations for preoperative cardiac testing. Results have implications for implementation, management, and practitioner adherence to published guidelines.     

Provision of hepatitis B vaccination for primary care dental staff in Scotland

OBJECTIVES: All dental surgeons should be protected from hepatitis B virus (HBV) infection by immunisation, ideally administered and monitored via occupational health services (OHS). This study examined relevant OHS systems in place for dental primary care healthcare workers (DHCW) across all Health Board Areas (HBAs) in Scotland. It also explored the DHCWs' knowledge of, and access to, these systems in three HBAs. METHODS: Data from senior staff in all Scottish Health Boards and Primary Care Trusts were collected by self-completing questionnaires. Information from DHCWs was collected via telephone interviews with General Dental Practitioners (GDPs) and Community Dental Officers (CDOs) in each of Ayrshire and Arran, Highland and Lothian Health Boards. RESULTS: Thirteen of the 15 HBAs had robust HBV vaccination and monitoring systems. However, only 7/15 (47%) of these covered all DHCWs. Seven HBAs provided vaccination and monitoring for CDOs only, leaving GDPs to undertake these responsibilities for themselves. Of the 105 DHCWs approached, 82 gave an interview. These interviews highlighted major differences between HBAs in relation to access of DHCWs to OHS and indicated that CDOs had greater access than GDPs to OHS. Overall, 31% of DHCWs were not satisfied with the OHS available. CONCLUSION: In order to safeguard both staff and patients, significant further work is required to ensure that all DHCWs have access to appropriate OHS support for provision and monitoring of immunisation procedures and related functions such as management of sharps injuries.     

Immortalization and characterization of human cell lines with mast cell and monocytic properties

Summary. We have previously derived a cell strain which had both mast cell and monocytic properties from the bone marrow of a child with diffuse cutaneous mastocytosis. This cell strain, termed HBM-M, consisted of two cell populations both of which possessed certain ultrastructural, cytochemi-cal and surface phenotypic features of degranulated mast cells. The cells also displayed cytochemical and surface phenotypic features of monocytes. These cells may represent a common bone marrow derived mast cell/monocyte precursor. Studies of human mast cells have been hindered by the fact that it is difficult to establish such cells in long-term culture. Thus, we sought to immortalize HBM-M cells by introducing Simian virus 40 large T-antigen. Following transfection by the strontium phosphate technique, transformed cells were selected, expanded and passaged until the cells entered a non-proliferative phase termed crisis. Certain clones passed through crisis 3 months later and by this means two immortal cell lines, HBM-MI-1 and HBM-MI-2, were obtained. The criterion for immortality was growth for greater than 100 population doublings. The immortal cell lines retained some, but not all. of the mast cell and monocytic properties of the original HBM-M cell strain. The immortalization of the cell strain HBM-M provides an opportunity to investigate the mast cell and monocytic properties of these cells, and the apparent relationship between mast cells and monocytes.     

Substrate for endothelial prostacyclin production in the presence of platelets exposed to collagen is derived from the platelets rather than the endothelium

Interactions between vascular endothelial cells and blood platelets have been investigated using a model microcirculation consisting of microcarrier beads colonized with human umbilical vein endothelial cells (HUVECs) and perfused with washed platelet suspensions. To simulate the effects of endothelial desquamation and exposure of subendothelium, fibrillar collagen in suspension was coinjected with the platelets. In this model, neither the passage of platelets alone nor collagen alone stimulated prostacyclin (PGI2) production by the HUVECs. Platelets activated by coinjection with collagen released thromboxane A2 (TXA2), and this was associated with the simultaneous production of PGI2 by the HUVECs. By means of double-isotope experiments with [3H]arachidonic acid (AA) incorporated into platelets and [14C]-AA into HUVECs, it was shown that all the PGI2 generated was derived from platelet AA and/or endoperoxides. This interpretation was strengthened by the finding that PGI2 production was not prevented by treatment of HUVECs with indomethacin followed by perfusion with collagen-stimulated platelets. AA metabolites in double-isotope label experiments were further characterized by reverse-phase chromatography, and it was shown that both cyclooxygenase and lipoxygenase products of the HUVECs were derived from platelet membrane lipid. Thrombin regularly produced transient PGI2 release, but showed rapid tachyphylaxis. Platelet-derived compounds including ADP, ATP, and platelet-activating factor (PAF) did not produce PGI2 release by HUVECs in this system. Thus, the transfer of AA and metabolites from collagen- stimulated platelets is likely to be the mechanism for PGI2 production in the context of minor degrees of endothelial desquamation.     

IL-33 signaling contributes to the pathogenesis of myeloproliferative neoplasms

Myeloproliferative neoplasms (MPNs) are characterized by the clonal expansion of one or more myeloid cell lineage. In most cases, proliferation of the malignant clone is ascribed to defined genetic alterations. MPNs are also associated with aberrant expression and activity of multiple cytokines; however, the mechanisms by which these cytokines contribute to disease pathogenesis are poorly understood. Here, we reveal a non-redundant role for steady-state IL-33 in supporting dysregulated myelopoiesis in a murine model of MPN. Genetic ablation of the IL-33 signaling pathway was sufficient and necessary to restore normal hematopoiesis and abrogate MPN-like disease in animals lacking the inositol phosphatase SHIP. Stromal cell–derived IL-33 stimulated the secretion of cytokines and growth factors by myeloid and non-hematopoietic cells of the BM, resulting in myeloproliferation in SHIP-deficient animals. Additionally, in the transgenic JAK2^V617F model, the onset of MPN was delayed in animals lacking IL-33 in radio-resistant cells. In human BM, we detected increased numbers of IL-33–expressing cells, specifically in biopsies from MPN patients. Exogenous IL-33 promoted cytokine production and colony formation by primary CD34⁺ MPN stem/progenitor cells from patients. Moreover, IL-33 improved the survival of JAK2^V617F-positive cell lines. Together, these data indicate a central role for IL-33 signaling in the pathogenesis of MPNs.