The efficacy of social role models to increase motivation to obtain vaccination against hepatitis B among men who have sex with men.

This study assessed the effects of role models in persuasive messages about risk and social norms to increase motivation to obtain hepatitis B virus (HBV) vaccination in men who have sex with men (MSM). MSM at risk for HBV in The Netherlands (N = 168) were recruited online via a range of websites and were randomly assigned to one of four conditions in a 2 (risk communication: yes and no) × 2 (social norms communication: yes and no) factorial design. In each condition, participants subsequently provided self-completed assessments of their perceived risk of HBV infection, perceived social norms regarding HBV vaccination and their intention to obtain vaccination against HBV. Risk communication and social norms communication that used social role models were effective in significantly increasing men's intention to obtain vaccination against HBV. No additive effect was found for a combined message. Mediation analyses showed that communications influenced intention via perceived risk and social norms. Findings extend previous theorizing and research and show that both role model-based risk communication and social norms communication can be effective in increasing intentions to obtain HBV vaccination in MSM. This knowledge contributes to the development of effective health promotion to increase HBV vaccination in MSM.

Do we understand trends in atmospheric sulfur species?

Anomalies appear to exist in our understanding of atmospheric sulfur compounds, specifically as evidenced in the time trends of the different chemical forms of these compounds. Trends determined at a number of locations by several different groups seem to indicate that, responding to emission reductions across North America, the concentration of SO2 in the atmosphere is declining more rapidly than that of aerosol SO4(2-). A number of possible reasons for this discrepancy are examined, but it is not possible to provide a definitive answer at this stage. The intent is to stimulate debate, because shortcomings in our understanding of the processes involved could have profound implications for the credibility of abatement strategies and policies for both acid deposition and fine particulate matter (PM).

Cyclopentenyl cytosine induces apoptosis and increases cytarabine-induced apoptosis in a T-lymphoblastic leukemic cell-line.

Cyclopentenyl cytosine (CPEC) is a nucleoside-analogue that decreases the concentrations of cytidine triphosphate (CTP) and deoxycytidine triphosphate (dCTP) in leukemic cells by inhibiting the enzyme CTP synthetase, resulting in a decreased synthesis of RNA and DNA. Low concentrations of dCTP facilitate the phosphorylation of 1-beta-D arabinofuranosyl cytosine (araC) and the incorporation of arabinofuranosyl cytosine triphosphate (araCTP) into DNA. Apoptosis and necrosis were analyzed by flow cytometric detection of fluorescence-labeled Annexin V in a human T-lymphoblastic MOLT-3 cell-line after incubations with CPEC and/or araC. CPEC induced apoptosis and necrosis in a concentration- (50-300 nM) and time-dependent (8-16 h) way. The observed necrosis proved to be secondary to apoptosis as the caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone (zVAD-fmk) completely blocked the CPEC-induced apoptosis and necrosis. Coincubation of various concentrations of CPEC and araC for 16h showed a significant additive effect on the occurrence of apoptosis and (secondary) necrosis. In contrast, a preincubation with 37.5 nM of CPEC for 24 h, which by itself caused only minor apoptosis (4%), followed by a coincubation for 16 h with 62.5 nM of araC (7% of apoptotic cells), showed a synergistic effect on the induction of apoptosis (27%, P<0.001). Growth-inhibition experiments with CPEC and araC under various conditions showed an additive effect on the araC-induced growth-inhibition after 48 h. The results indicate that the cytotoxicity of araC can be increased in T-lymphoblasts by CPEC.

The role of thrombopoietin in post-operative thrombocytosis.

Thrombopoietin (Tpo), the main regulator of thrombocytopoiesis, is a probable candidate to play a role in the increase in platelet counts that is frequently seen after surgery. In the current study, serial blood samples of patients that underwent major surgery were analysed with respect to Tpo kinetics, platelet turnover and inflammatory cytokines. Platelet Tpo content and plasma Tpo levels rose before platelet counts increased, suggesting that Tpo was indeed responsible for the elevation in platelet counts. In addition, an increase in interleukin 6 (IL-6) levels, but not in IL-11 and tumour necrosis factor alpha levels, was seen before the rise in Tpo concentration. In vitro, IL-6 was shown to enhance Tpo production by the HepG2 liver cell line. Thus, increased Tpo levels after surgery, possibly resulting from enhanced Tpo production under the influence of IL-6 or other inflammatory cytokines, are involved in an enhanced thrombocytopoiesis.

Identifying relevant diagnostic studies in MEDLINE. The diagnostic value of the erythrocyte sedimentation rate (ESR) and dipstick as an example.

OBJECTIVE: We aimed to examine sensitivity and positive predictive value of MEDLINE searching for diagnostic studies, relevant for the primary health care setting. METHOD: Results of MEDLINE searches were compared with a reference standard collection of studies on two subjects, the diagnostic value of ESR in discriminating between 'pathology' and 'no pathology', and the dipstick method in diagnosing urinary tract infections. The main outcome measures were sensitivity (proportion of the total number of reference standard diagnostic studies that could be identified by the search) and positive predictive value (proportion of the total number of publications retrieved by MEDLINE that were incorporated in the reference standard). RESULTS: The combined MeSH and freetext search was more sensitive than MeSH term searching only, for both the ESR and the dipstick search. With this combined search sensitivities of 0.91 and 0.98 and predictive values of 0.10 and 0.68 were found for ESR and dipstick respectively. By restricting the search with keywords describing the primary health care setting the predictive values increased to 0.72 and 1.00 but sensitivity dropped to 0.10 and 0.07 (ESR and dipstick respectively). CONCLUSION: Combining freetext and MeSH term searching, without restriction to the primary health care setting, is a valuable strategy in systematically searching for available evidence on the value of a diagnostic test in the scope of a specific disease. The predictive value seems to depend on the breadth of the disease area. MEDLINE should provide a term such as 'diagnostic evaluation study' to be used in the limit field Publication Type to specify diagnostic studies.

A simple and sensitive method for determining plasma cell isotype and monoclonality in bone marrow using flowcytometry.

In this paper we describe a new, rapid and sensitive method to determine plasma cell isotype and clonality in bone marrow using flowcytometry. With the use of a new fixation and permeabilization reagent (Permeafix), which preserves cell structure and morphology, and a monoclonal antibody (Mab) specific for plasma cells (B-B4), it has become possible to specifically select plasma cells and to determine the cytoplasmatic immunoglobulins by flowcytometry. Thirty successive bone marrow aspirates from multiple myeloma patients and patients with MGUS were studied as well as 10 bone marrow samples from patients with reactive plasmacytosis. Each sample was analysed both by immunofluorescence on cytospin smears and FACS analysis. There were no discrepancies between plasma cell isotype as determined by FACS and cytospin. Moreover, FACS analysis was shown to allow detection of very low numbers of plasma cells and to determine whether these plasma cells are mono- or polyclonal. Possible applications are discussed.

Significance of lymphoblasts in cerebrospinal fluid in newly diagnosed pediatric acute lymphoblastic malignancies with bone marrow involvement: possible benefit of dexamethasone.

We analyzed retrospectively the data on 135 children treated since 1983 for acute lymphoblastic leukaemia and non-Hodgkin's lymphoma with bone marrow involvement with respect to the presence of lymphoblasts in cerebrospinal fluid (CSF) and the number of cells in CSF, both at initial diagnosis and during follow-up. Of these children 96, 11, and 28 suffered from B-progenitor, mature B cell, and T-cell malignancies respectively. In two patients initial central nervous system involvement was documented by the presence of lymphoblasts with high CSF cell counts (B+C+ patients); 19 patients had CSF lymphoblasts with normal CSF cell counts (B+C- patients); the others had no CSF blasts and normal CSF cell counts (B-C- patients). In B+C- and B-C- patients 5-year-leukaemia-free survival was 66 and 70%, respectively (i.e., not significantly different). None of the B+C- patients experienced a first relapse in the central nervous system. Differences in outcome by comparing with reports of others may be related to the use of dexamethasone instead of prednisone in almost all of our patients.

Diagnosing dementia: a comparison between a monodisciplinary and a multidisciplinary approach.

Discrepancies were examined in diagnostic outcome between a monodisciplinary approach and a multidisciplinary, criteria-based approach in patients referred to a university memory clinic. Of 278 patients not fulfilling dementia criteria, 19 had been previously diagnosed as demented (specificity: 0.93). In 60 of 152 demented patients, dementia had not been diagnosed before (sensitivity: 0.61). Underreporting was frequent for mildly demented patients and for patients with coexisting depressive symptoms. In patients referred by psychiatrists, sensitivity rates for dementia and Alzheimer's disease were low; in patients referred by neurologists, depression often went unreported. Results underscore the need for more frequent use of integrated multidisciplinary services for cognitively disturbed patients.

Monoclonal antibodies against myeloperoxidase are valuable immunological reagents for the diagnosis of acute myeloid leukaemia.

Whereas the diagnosis of acute lymphoid leukaemia greatly depends on immunophenotyping on the leukaemic cells, the diagnosis of acute myeloid leukaemia (AML) is still only based on morphological and cytochemical criteria. Here we describe that with a monoclonal antibody, directed against myeloperoxidase (MPO), the immunological diagnosis of AML is possible in most cases. A monoclonal antibody against lactoferrin (LF) was used to detect more mature myeloperoxidase-containing cells. Of the cell samples tested from 206 different patients with AML, 95% were found to express myeloperoxidase in more than 15% of lactoferrin-negative cells. Compared with other myeloid-reactive monoclonal antibodies (VIM2, anti-CD13, anti-CD14, anti-CD15 and anti-CD33), a higher diagnostic sensitivity and specificity for AML was found. No significant correlation with the FAB classification was found. In most patients, more MPO-positive cells were detected by the monoclonal antibody than by the cytochemical staining. This could be due to the recognition of enzymatically inactive precursor forms of myeloperoxidase by the antibody. The use of anti-myeloperoxidase monoclonal antibodies for the diagnosis of AML has the advantage that objective quantification is possible.

Serum erythropoietin (ESF) titers in anemia of chronic renal failure.

ESF titers were determined in 99 patients of various stages of chronic renal failure, by using the fetal mouse liver cell bioassay. Of these patients 45 were receiving conservative therapy and 54 on maintenance hemodialysis. ESF levels were significantly below normal in both groups of patients. A significant inverse relationship was found between hemoglobin concentration and ESF level in the predialysis patients with chronic glomerulonephritis. No correlation was found between both parameters in the predialysis patients with chronic nonglomerular renal disease. A significant positive correlation was found between hemoglobin concentration and ESF level in nephric dialysis patients who were transfusion independent. Transfusion-dependent nephric dialysis patients had lower hemoglobin concentrations and lower ESF levels before transfusion than did nephric dialysis patients who were transfusion independent. In nephric dialysis patients ESF levels fell sharply after blood transfusion, whereas in anephric dialysis patients such a physiologic ESF response was not found. It was concluded that despite the presence of an absolute ESF deficiency in all anemia uremic patients, this anemia cannot be explained by ESF deficiency alone. The increasing degree of anemia found in predialysis patients with deteriorating renal function appears to be primarily caused by factors other than ESF deficiency, the most likely being accumulation of uremic inhibitors of erythropoiesis. In dialysis patients in whom inhibitor levels are relatively homogeneous, the degree of anemia appears to be directly related to the residual capability of the kidney or the extrarenal sites to produce ESF.

Serum erythropoietin (EST) titers in anemia.

Erythropoietin (ESF) titers were determined in sera from patients with different types of anemia using the fetal mouse liver cell bioassay. An inverse relationship was found between hemoglobin concentration and ESF titer. However, ESF titers differed markedly between patients at comparable degrees of anemia. Several groups of patients were distinguished on the basis of the activity of their erythroid bone marrow. In each of these groups, a significant negative correlation was found between the hemoglobin concentration and the logarithm of the ESF titer. ESF titers in patients with pure red cell aplasia were fourfold higher than those in patients with iron-deficiency anemia and tenfold higher than those in patients with megaloblastic anemia and homozygous sickle cell anemia at comparable hemoglobin concentrations. Following the initiation of specific therapy in patients with pernicious anemia and patients wit iron-deficiency anemia, serum ESF titers were found to decrease prior to any substantial rise in hemoglobin concentrations. In the patients with pernicious anemia, the lowest ESF levels were found 1 day after administration of vitamin B12, whereas in the patients with iron-deficiency anemia, the lowest ESF levels were reached in the second week of oral iron therapy. ON the basis of these data it was concluded that serum ESF titers in anemic patients are not only inversely related to the hemoglobin concentration but also to the activity of the erythroid bone marrow.

Serum erythropoietin (ESF) titers in polycythemia.

Serum ESF titers were measured in 42 polycythemic patients using the fetal mouse liver cell bioassay. ESF titers in patients with secondary polycythemia differed significantly from those in patients with polycythemia vera (p less than 0.0001). Among the 21 patients with secondary polycythemia, 1 patient had an ESF titer less than 10 mU/ml (the lower limit of sensitivity) and 20 had ESF titers that ranged between 11 and 112 mU/ml, with a mean titer of 56 mU/ml. Among the 21 patients with polycythemia vera, 13 patients had ESF titers less than 10 mU/ml and 8 had ESF titers ranging between 12 and 55 mU/ml, with a mean titer of 26 mU/ml. The mean hemoglobin concentration in the 8 patients with ESF titers greater than 10 mU/ml was significantly below that in the 13 polycythemia vera patients with ESF titers less than 10 mU/ml (p less than 0.03). If ESF titers less than 10 mU/ml had been indicative of polycythemia vera and ESF titers greater than 10 mU/ml had been indicative of secondary polycythemia in patients with hemoglobin concentrations greater than 17.7 g/dl, but not indicative of either condition in patients with hemoglobin concentrations less than 17.7 g/dl, 71.5% of the polycythemic patients in this study would have been diagnosed correctly, 9.5% incorrectly, and in the 19% the diagnosis would have remained uncertain. It was concluded that measurement of serum ESF titers using this in vitro bioassay can be of clinical importance in differentiating between polycythemia vera and secondary polycythemia.

Comparison of the hemagglutination inhibition assay kit for erythropoietin (ESF) with the fetal mouse liver cell bioassay in vitro.

The commercially available hemagglutination inhibition (HAI) assay kit for erythropoietin (ESF) was compared with the fetal mouse liver cell (FMLC) bioassay. No correlation was obtained ESF levels determined by both methods in a variety of pathologic sera. The HAI kit showed a great batch variability. Significant immunoreactivity was found in those fractions of a normal human serum and a human urinary ESF preparation that were not active in the FMLC bioassay. A very poor recovery of immunoreactivity was found when the international reference preparation for erythropoietin (second IRPE) was added to a normal human serum.