Relationships among Type A behavior,employment experiences,and gender: The Minnesota heart survey

Previous studies indicate that Type A behavior is more prevalent among men than women. This sex difference may reflect variations in men's and women's job experiences, some of which may act as catalysts for Type A behavior. This study examines the relationship of Type A behavior (measured by the Jenkins Activity Survey) to men's and women's work hours, occupational mobility, and job-related interactions, using data from a population-based survey of 2512 employed men and women conducted in Minneapolis-St. Paul, Minnesota, between 1980 and 1982. Among both sexes, Type A behavior is related to long work hours, high occupational mobility, and nonsupportive interactions with co-workers, all job experiences more common for men than for women. No sex differences are found in the relationships between Type A behavior and these job experiences. Also, no sex difference is observed in the unadjusted Type A scores or in these scores when either age, education, or marital status is taken into account. The expected direction of the sex difference in Type A behavior is reversed when work hours are controlled: women have a higher Type A score than men when work hours are considered.This work was supported in part by Grants 2T32-HL07328 and 2R01-HL23727 from the National: Heart, Lung, and Blood Institute. This work was completed while the lead author was a. postdoctoral fellow at the University of Minnesota, Division of Epidemiology, School of Public Health.     

The factors controlling stem cell recirculation. i. Migration of hemopoietic stem cells in adrenalectomized mice

The influence of bilateral adrenalectomy on hemopoietic stem cell (CFU) migration in mice has been studied. Formation of endogenous spleen colonies in lethally irradiated, leg-shielded mice was sharply increased by prior adrenalectomy, and this increase was not dependent on the volume of shielded bone marrow. Adrenalectomy was shown to increase endogenous spleen colony formation in sublethally irradiated mice as well. However, it had no affect on formation of spleen colonies in lethally irradiated mice injected with syngeneic bone marrow. The CFU content of murine bone marrow decreased acutely after removal of the adrenals, and this decrease was accompanied by a concomitant increase in the peripheral blood and splenic CFU. Thus, adrenalectomy appeared to have no affect on the splenic plating efficiency or proliferative rate of hemopoietic stem cells, but it did result in increased migration of stem cells from the bone marrow to the blood, and thence to the spleen. It is concluded that the adrenal steroids may be of physiologic importance in the regulation of ehmopoietic stem cell migration.     

Predictors of non-adoption of cigarette smoking following experimentation

The Childhood Antecedents of Smoking Study (CASS) investigated patterns of cigarette smoking among junior and senior high school students in an upper midwest school district. Four biannual school-based surveys were conducted over two years. A cohort of 72 smokers was identified and followed to determine who continued smoking and who quit. Discriminant analysis was used to study social, psychological, and environmental factors predictive of quitting smoking. Compared to continuing smokers, quitters reported having fewer friends and siblings who smoked, they were less likely to view the cigarette smoker's image as positive, and lived in families where parental involvement with teenagers was high (based on the reports of parents). These results are consistent with the view that social influences are strong determinants of patterns of adolescent smoking behaviour.     

Trends in smoking among adults from 1980 to 2009: the Minnesota heart survey

Objectives. We examined population-based smoking trends in Minnesota between 1980 and 2009.Methods. The Minnesota Heart Survey (MHS) is a population-based, serial, cross-sectional study of cardiovascular risk factor trends among Minneapolis–Saint Paul metropolitan residents. The MHS recently completed its sixth survey (1980–1982 [n = 3799], 1985–1987 [n = 4641], 1990–1992 [n = 5159], 1995–1997 [n = 6690], 2000–2002 [n = 3281], and 2007–2009 [n = 3179]). We used MHS data to examine smoking trends among adults aged 25 to 74 years by means of age-adjusted generalized linear mixed models.Results. Between 1980 and 2009, the prevalence of current smoking decreased from 32.8% to 15.5% for men and from 32.7% to 12.2% for women (P < .001 for each). Greater decreases occurred among those with higher income and those with more education. Among currently smoking men, the number of cigarettes smoked per day decreased from 26.0 in the 1980–1982 survey to 16.0 in the 2007–2009 survey (P < .001). Similar trends were observed among women.Conclusions. Although the prevalence of smoking and cigarette consumption decreased from the 1980–1982 period to the 2007–2009 period, interventions specifically designed for those of lower socioeconomic status are needed.The harmful cardiovascular effects of cigarette smoking are well established, and many interventions have been implemented to reduce the prevalence of smoking. These interventions include those that target individuals, such as the development of new behavioral approaches and smoking-cessation drugs,^1–3 as well as population-level interventions, including taxation on cigarettes, stricter advertising laws, increased education, and restricted smoking in public.^4–7 Although these interventions have been associated with decreased prevalence of smoking, a substantial subset of the population continues to smoke, and cigarette smoking continues to be an important public health issue. Changes in smoking practices and the identification of those most likely to smoke have important clinical and public health implications. This information is also essential for the design of future smoking-cessation interventions.Our primary objective was to describe population trends in smoking and smoking practices, such as the quantity of cigarettes smoked and the reported age at smoking initiation, using population-based data from the Minnesota Heart Survey (MHS). Our secondary objective was to examine whether smoking trends varied among those with different demographic characteristics, including age, gender, race, and socioeconomic status (SES).     

Biochemical and pharmacological characterization of AZD1981, an orally available selective DP2 antagonist in clinical development for asthma

Background and Purpose

The discovery of DP₂ as a second receptor for PGD₂ has prompted the search for antagonists as potential novel therapies based on the associations between PGD₂ and disease. Here we describe the biochemical and pharmacological properties of 4-(acetylamino)-3-[(4-chlorophenyl)thio]-2-methyl-1H-indole-1-acetic acid (AZD1981), a novel DP₂ receptor antagonist.

Experimental Approach

Binding to DP₂, functional receptor pharmacology and selectivity were studied in both human and animal systems.

Key Results

AZD1981 displaced radio-labelled PGD₂ from human recombinant DP₂ with high potency (pIC₅₀ = 8.4). Binding was reversible, non-competitive and highly selective against a panel of more than 340 other enzymes and receptors, including DP₁ (>1000-fold selective). AZD1981 inhibited DP₂-mediated shape change and CD11b up-regulation in human eosinophils, shape change in basophils and chemotaxis of human eosinophils and Th2 cells with similar potency. AZD1981 exhibited good cross-species binding activity against mouse, rat, guinea pig, rabbit and dog DP₂. Evaluation in mouse, rat or rabbit cell systems was not possible as they did not respond to DP₂ agonists. Agonist responses were seen in guinea pig and dog, and AZD1981 blocked DP₂-mediated eosinophil shape change. Such responses were more robust in the guinea pig, where AZD1981 also blocked DP₂-dependent eosinophil emigration from bone marrow.

Conclusions and Implications

AZD1981 is a DP₂ antagonist that blocks functional responses in eosinophils, Th2 cells and basophils. It exhibited similar potency irrespective of the cell type, DP₂ agonist or species used. This selective orally active agent is currently under clinical evaluation as a potential therapeutic agent in respiratory diseases including asthma.     

Human thrombopoietin levels are high when thrombocytopenia is due to megakaryocyte deficiency and low when due to increased platelet destruction

Thrombopoietin (TPO), the ligand for c-mpl, stimulates proliferation of committed megakaryocytic progenitors and induces maturation of megakaryocytes. To better understand factors regulating TPO levels, we measured blood levels of TPO in patients with impaired platelet production due to aplastic anemia (AA) and with platelet destructive disorders, including idiopathic thrombocytopenic purpura (ITP), posttransfusion purpura (PTP), drug purpura (DP), and X-linked thrombocytopenia (XLTP). The TPO receptor capture enzyme immunoassay (EIA) used had a detection limit of integral of approximately-150 to 200 pg/mL. TPO was undetectable in 88 of 89 normal individuals. Eighteen of 19 patients with AA and a mean platelet count (MPC) of 18,000/microliters (2,000 to 61,000/microliters) had markedly elevated TPO levels (mean, 1,467 pg/mL; range, 597 to 3,834 pg/mL). Eight AA patients who responded to immunosuppressive therapy with their MPC increasing to 140,000/microliters (92,000 to 175,000/microliters) had substantial decreases in TPO (mean, 440 pg/mL; range, 193 to 771 pg/mL). Initial TPO levels did not differ significantly between responders and nonresponders. In contrast, all 21 patients with ITP and an MPC of 16,000/microliters (1,000 to 51,000 /microliters) had undetectable TPO levels, as did 6 patients with acute PTP or DP and 2 patients with XLTP. Megakaryocyte mass, reflected in the rate of platelet production, appears to be the major determinant of TPO levels in thrombocytopenic patients rather than circulating platelet levels per se. Measurement of serum TPO may be useful in differentiating thrombocytopenias due to peripheral destruction from those due to thrombopoietic failure.     

Endovascular management of pseudoaneurysms of the splenic artery: experience with six patients

The purpose of this paper was to describe our experience with the endovascular management of splenic artery pseudoaneurysms (SAPA). Seven patients with documented SAPA on CT and/or angiography were considered for endovascular treatment. The pseudoaneurysms were located in the main splenic artery (n = 4) or its branches (n = 3). In one patient in whom the pseudoaneurysm was located in a hilar branch, selective catheterization of splenic artery failed. Metallic coils (n = 1), gelfoam and hydrogel particles (n = 1), metallic coils and gelfoam (n = 2), metallic coil, gelfoam and acrylic glue (n = 2) were used as embolization material in the remaining six patients. These patients were followed for a mean period of 11.3 months. Transcatheter embolization was successful in five patients with no procedure‐related complications. In one patient, embolization was incomplete and the patient underwent surgery, but died on the 10th postoperative day because of irreversible shock. Another patient, after successful embolization, underwent surgery for management of an associated pseudocyst. Endovascular treatment is a safe and effective method of management of SAPA.