Multiple Influences on Cognitive Function Among Urban-Dwelling African Americans.

This study examined multiple influences on cognitive function among African Americans, including education, literacy, poverty status, substance use, depressive symptoms, and cardiovascular disease (CVD) risk factors. Baseline data were analyzed from the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) study. Participants were 987 African Americans (mean age 48.5 years, SD = 9.17) who completed cognitive measures assessing verbal learning and memory, nonverbal memory, working memory, verbal fluency, perceptuo-motor speed, attention, and cognitive flexibility. Using preplanned hierarchical regression, cognitive performance was regressed on the following: (1) age, sex, education, poverty status; (2) literacy; (3) cigarette smoking, illicit substance use; (4) depressive symptoms; and (5) number of CVD risk factors. Results indicated that literacy eliminated the influence of education and poverty status in select instances, but added predictive utility in others. In fully adjusted models, results showed that literacy was the most important influence on cognitive performance across all cognitive domains (p < .001); however, education and poverty status were related to attention and cognitive flexibility. Depressive symptoms and substance use were significant predictors of multiple cognitive outcomes, and CVD risk factors were not associated with cognitive performance. Overall, findings underscore the need to develop cognitive supports for individuals with low literacy, educational attainment, and income, and the importance of treating depressive symptoms and thoroughly examining the role of substance use in this population.

The safety and efficacy of vertebroplasty using Cortoss cement in a newly established vertebroplasty service.

Vertebroplasty provides an effective means of treating painful vertebral lesions although the majority of the literature relates to vertebroplasty using PMMA cement. The purpose of this study is to assess the safety and efficacy of vertebroplasty using Cortoss, a recently developed bis-GMA resin. Our newly established vertebroplasty service exclusively uses Cortoss cement and has a patient database which is updated on a regular basis using the medical records. To date, there are 34 patients on this database, mean age 66, in whom a vertebroplasty has been performed on 42 vertebral lesions with a mean of 2.2 ml of Cortoss injected into each lesion. The mean duration of follow up was 9.5 months. Eighty-two per cent of patients reported an improvement in their symptoms, while 79% required less analgesia post vertebroplasty. A total of 88.2% experienced no significant complications. In 38% there was an asymptomatic leakage of Cortoss. Four patients (11.8%) experienced significant complications: one asymptomatic PE, one episode of transient radicular leg pain, one generalized rash and one patient suffered retropulsion of the Cortoss due to further vertebral malignancy. Cortoss vertebroplasty provides comparable efficacy and safety to the published literature for PMMA.

Applying genomics-related technologies for Africa's health needs.

While the past century has seen significant improvement in life expectancies in the developed world, it has also witnessed diseases like HIV/AIDS, malaria and tuberculosis ravage populations in the developing world. In some Sub-Saharan African countries, life expectancies have plummeted to less than 40 years--nearly half of those in developed countries. Unequal access to the benefits of science and technology, including medical advances, exacerbate this disparity. In order to address the challenge of global health inequities and strengthen the role of science and technology innovation in contributing to real solutions, the Canadian Program on Genomics and Global health (CPGGH), based at the University of Toronto, has identified three guiding questions: Which genomics-related technologies are most likely to improve the health of people in developing countries?; How can developing countries harness these technologies for health development?; and What can industrialized countries do to assist developing countries?

New insights into onset mechanisms of atrial fibrillation and flutter after coronary artery bypass graft surgery.

OBJECTIVE: To determine by means of a monitoring study the onset mechanisms of atrial fibrillation (AF) after coronary artery bypass graft surgery (CABG). PATIENTS AND DESIGN: During elective CABG, 81 patients had one bipolar atrial and one ventricular epicardial electrode attached. These were connected to a Vitatron 900E external pacing device, which monitored the patients for four consecutive days. 12 lead ECGs were obtained if AF was clinically detected and Holter ECGs were obtained in 8 (33%) of these patients. RESULTS: 24 patients (30%) developed paroxysmal AF (50%), atrial flutter (17%), or both (33%). The number of AF episodes varied from 1-169 a day (median 5) and were usually of short duration (median 2.25 minutes). Pacemaker diagnostics showed much intrapatient and interpatient variability in onset mechanisms but the majority of AF onsets (71%) were preceded by either short runs of AF or multiple atrial extrasystoles. The final trigger was a conducted atrial extrasystole in 72% of cases. There were no bradycardic triggers. The Holter ECGs confirmed the device's data. CONCLUSIONS: The onset mechanisms of post-CABG AF are dominated by atrial extrasystoles with multiple atrial extrasystoles and short runs of AF preceding the main AF onset in the majority of cases. These results have major implications for the development of new preventive pacing algorithms.

Multifocal osteonecrosis -- a case report.

The pathogenesis of idiopathic multifocal osteonecrosis is poorly understood. It is difficult to diagnose with conventional radiography or computed tomography and poses a great management challenge. A case of idiopathic multifocal osteonecrosis is presented in a young boy illustrating the difficulties in the management of such patients.

Using an artificial neural network to predict healing times and risk factors for venous leg ulcers.

OBJECTIVES: This study aimed to identify the risk factors that influence the healing process of venous leg ulcers treated with compression bandaging, with a view to predicting healing time. METHOD: A retrospective cohort study was performed on data collected prospectively on 325 consecutive patients presenting with 345 venous ulcers at the Salford Primary Care Trust leg ulcer clinic between January 1997 and December 1999. Use of an artificial neural network (ANN) technique accurately predicted the healing times for 68% of the patients. RESULTS: The ANN demonstrated that healing was significantly related to a history of previous leg ulceration, 'quite wet' ulcer exudate, high body mass index, large initial total ulcer area, increasing age and male gender. CONCLUSION: The ability to identify at presentation ulcers that might be resistant to standard therapy would allow early consideration of more radical treatments such as hospitalisation, wound debridement or venous surgery.

Evidence from immunoneutralization and antisense studies that the inhibitory actions of glucocorticoids on growth hormone release in vitro require annexin 1 (lipocortin 1).

1. Our previous studies have identified a role for annexin 1 as a mediator of glucocorticoid action in the neuroendocrine system. The present study centred on growth hormone (GH) and exploited antisense and immunoneutralization strategies to examine in vitro the potential role of annexin 1 in effecting the regulatory actions of glucocorticoids on the secretion of this pituitary hormone. 2. Rat anterior pituitary tissue responded in vitro to growth hormone releasing hormone, forskolin, 8-Bromo-cyclic adenosine 3'5'-monophosphate (8-Br-cyclic AMP) and an L-Ca(2+) channel opener (BAY K8644) with concentration-dependent increases GH release which were readily inhibited by corticosterone and dexamethasone. 3. The inhibitory actions of the steroids on GH release elicited by the above secretagogues were effectively reversed by an annexin 1 antisense oligodeoxynucleotide (ODN), but not by control (sense or scrambled) ODNs, as also were the glucocorticoid-induced increases in annexin 1. Similarly, a specific anti-annexin 1 monoclonal antibody quenched the corticosterone-induced suppression of secretagogue-evoked GH release while an isotype matched control antibody was without effect. 4. Transmission electron micrographs showed that the integrity and ultrastructural morphology of the pituitary cells were well preserved at the end of the incubation and unaffected by exposure to the ODNs, antibodies, steroids or secretagogues. 5. The results provide novel evidence for a role for annexin 1 as a mediator of the inhibitory actions of glucocorticoids on the secretion of GH by the anterior pituitary gland and suggest that its actions are effected at a point distal to the formation of cyclic AMP and Ca(2+) entry.

Annexin 1 (lipocortin 1) mediates the glucocorticoid inhibition of cyclic adenosine 3',5'-monophosphate-stimulated prolactin secretion.

Our previous studies have identified a role for annexin 1 (also called lipocortin 1) in the regulatory actions of glucocorticoids (GCs) on the release of PRL from the rat anterior pituitary gland. In the present study we used antisense and immunoneutralization strategies to extend this work. Exposure of rat anterior pituitary tissue to corticosterone (1 nM) or dexamethasone (100 nM) in vitro induced 1) de novo annexin 1 synthesis and 2) translocation of the protein from intracellular to pericellular sites. Both responses were prevented by the inclusion in the medium of an annexin 1 antisense oligodeoxynucleotide (ODN; 50 nM), but not by the corresponding sense and scrambled ODN sequences. Unlike the GCs, 17beta-estradiol, testosterone, and aldosterone (1 nM) had no effect on either the synthesis or the cellular disposition of annexin 1; moreover, none of the steroids or ODNs tested influenced the expression of annexin 5, a protein closely related to annexin 1. The increases in PRL release induced in vitro by drugs that signal via cAMP/protein kinase A [vasoactive intestinal polypeptide (10 nM), forskolin (100 microM), 8-bromo-cAMP (0.1 microM)] or phospholipase C (TRH, 10 nM) were attenuated by preincubation of the pituitary tissue with either corticosterone (1 nM) or dexamethasone (100 nM). The inhibitory actions of the steroids on the secretory responses to vasoactive intestinal polypeptide, forskolin, and 8-bromo-cAMP were specifically quenched by inclusion in the medium of the annexin 1 antisense ODN (50 nM) or a neutralizing antiannexin 1 monoclonal antibody (antiannexin 1 mAb, diluted 1:15,000). By contrast, the ability of the GCs to suppress the TRH-induced increase in PRL release was unaffected by both the annexin 1 antisense ODN and the antiannexin 1 mAb. In vivo, interleukin-1beta (10 ng, intracerebroventricularly) produced a significant increase in the serum PRL concentration (P < 0.01), which was prevented by pretreatment of the rats with corticosterone (100 microg/100 g BW, sc). The inhibitory actions of the steroid were specifically abrogated by peripheral administration of an antiannexin 1 antiserum (200 microl, sc); by contrast, when the antiserum was given centrally (3 microl, intracerebroventricularly), it was without effect. These results support our premise that annexin contributes to the regulatory actions of GCs on PRL secretion and suggest that it acts at point distal to the formation of cAMP.

Shear and time-dependent changes in Mac-1, LFA-1, and ICAM-3 binding regulate neutrophil homotypic adhesion.

We examined the relative contributions of LFA-1, Mac-1, and ICAM-3 to homotypic neutrophil adhesion over the time course of formyl peptide stimulation at shear rates ranging from 100 to 800 s-1. Isolated human neutrophils were sheared in a cone-plate viscometer and the kinetics of aggregate formation was measured by flow cytometry. The efficiency of cell adhesion was computed by fitting the aggregate formation rates with a model based on two-body collision theory. Neutrophil homotypic adhesion kinetics varied with shear rate and was most efficient at 800 s-1, where approximately 40% of the collisions resulted in adhesion. A panel of blocking Abs to LFA-1, Mac-1, and ICAM-3 was added to assess the relative contributions of these molecules. We report that 1) LFA-1 binds ICAM-3 as its primary ligand supporting homotypic adhesion, although the possibility of other ligands was also detected. 2) Mac-1 binding to an unidentified ligand supports homotypic adhesion with an efficiency comparable to LFA-1 at low shear rates of approximately 100 s-1. Above 300 s-1, however, Mac-1 and not LFA-1 were the predominant molecules supporting cell adhesion. This is in contrast to neutrophil adhesion to ICAM-1-transfected cells, where LFA-1 binds with a higher avidity than Mac-1 to ICAM-1. 3) Following stimulation, the capacity of LFA-1 to support aggregate formation decreases with time at a rate approximately 3-fold faster than that of Mac-1. The results suggest that the relative contributions of beta2 integrins and ICAM-3 to neutrophil adhesion is regulated by the magnitude of fluid shear and time of stimulus over a range of blood flow conditions typical of the venular microcirculation.

The role of the chair's spouse in academic departments of family medicine.

BACKGROUND AND OBJECTIVES: Family medicine has the highest percentage of unfilled budgeted faculty positions of all clinical and basic science departments. To successfully recruit and retain academic leaders, personal and professional issues need to be recognized and valued. This study reports the results of a national survey of chairs and an important, often overlooked factor in recruitment and retention--the spouse of the department chair. METHODS: Questionnaires were sent to 107 chairs of academic departments or divisions of family medicine and their spouses. RESULTS: There was a usable response rate of 86%, and data from 85 questionnaires (79%) were analyzed. The spouses' highest role priority was family, perhaps reflecting their relatively young mean age of 48.6 years. There was a statistically significant correlation between those who were "oriented" to the role of chair's spouse and a higher level of participation in departmental activities. Data are also reported on spouse role satisfaction, expectations, and factors in deciding to stay or leave their current location. CONCLUSIONS: The results suggest that with the increased competition for family physicians in a multitude of practice settings, search committees for family medicine department chairs need to be innovative and attentive to personal as well as professional factors in recruiting and retaining future and current department chairs. It would be prudent to acknowledge the role of the spouse in decisions concerning job selection and satisfaction.

A comparison of sub-bandage pressures produced with two multi-layer bandaging systems.

Fourteen nurses with experience in the use of high-compression bandaging were asked to bandage the same limb with two different bandaging systems: the 'Charing Cross' four-layer regimen (System A), and a modified system incorporating two new bandages (System B). A sub-bandage pressure monitor was used to quantify the efficacy of the resulting bandaging for the two systems. The results indicated that there was no significant difference between site sub-bandage pressures achieved using the two bandaging systems. Sub-bandage pressure profiles, however, fluctuated with patient posture, the best profiles being obtained with System B and the patient in the sitting position.

Beta2-integrins mediate stable adhesion in collisional interactions between neutrophils and ICAM-1-expressing cells.

The aggregation of human neutrophils in suspension has features that are analogous to their attachment to activated endothelium in that both involve selectin and beta2-integrin adhesion receptors. For the collisional interaction that forms neutrophil aggregates in suspension, there is a tethering step in which L-selectin on neutrophils binds PSGL-1. At relatively low shear rates (100-200 s(-1)) firm adhesion is mediated in equal measure by LFA-1 binding to ICAM-3, and Mac-1 binding to an as yet undefined ligand. In this report we used a mouse melanoma cell line expressing an estimated 700,000 ICAM-1 (CD54) to examine the relative roles of LFA-1 and Mac-1 over the kinetics of heterotypic cell adhesion in shear mixed suspensions. Neither heterotypic nor homotypic neutrophil aggregates formed with application of shear alone. However, the rate of aggregation peaked within seconds of chemotactic stimulation. In contrast to homotypic aggregation, neither L-selectin nor its O-glycoprotein ligands on neutrophils contributed to heterotypic adhesion. Adhesion was inhibited in a dose-dependent manner as ICAM-1 was titrated with blocking mAb. A direct interaction between LFA-1 and ICAM-1 was preferred over the first minute of stimulation, whereas at later times adhesion was supported equally by Mac-1. Activation with MnCl2 also favored participation of the constitutively expressed LFA-1. Application of defined shear in a cone and plate viscometer showed that adhesion to the ICAM-1 cells decreased from a maximum level to baseline as shear rate increased up to 400 s(-1) in a manner typical of integrin adhesion alone. In contrast, homotypic aggregation supported by the transition from selectin to integrin binding exhibited an increase in efficiency up to 800 s(-1). The pathophysiological significance of receptor site density and duration of contact in collisional interactions relevant to leukocyte recruitment compared to leukocyte-endothelial cell interactions on surfaces is discussed.

Hydrodynamic shear shows distinct roles for LFA-1 and Mac-1 in neutrophil adhesion to intercellular adhesion molecule-1.

The binding of neutrophil beta2 integrin to intercellular adhesion molecule-1 (ICAM-1) expressed on the inflamed endothelium is critical for neutrophil arrest at sites of tissue inflammation. To quantify the strength and kinetics of this interaction, we measured the adhesion between chemotactically stimulated neutrophils and ICAM-1-transfected mouse cells (E3-ICAM) in suspension in a cone-plate viscometer at shear rates typical of venular blood flow (100 s-1 to 500 s-1). The kinetics of aggregation were fit with a mathematical model based on two-body collision theory. This enabled estimation of adhesion efficiency, defined as the probability with which collisions between cells resulted in firm adhesion. The efficiency of beta2-integrin-dependent adhesion was highest ( approximately 0.2) at 100 s-1 and it decreased to approximately zero at 400 s-1. Both LFA-1 and Mac-1 contributed equally to adhesion efficiency over the initial 30 seconds of stimulation, but adhesion was entirely Mac-1-dependent by 120 seconds. Two hydrodynamic parameters were observed to influence integrin-dependent adhesion efficiency: the level of shear stress and the intercellular contact duration. Below a critical shear stress (<2 dyn/cm2), contact duration predominantly limited adhesion efficiency. The estimated minimum contact duration for beta2-integrin binding was approximately 6.5 ms. Above the critical shear stress (>2 dyn/cm2), the efficiency of neutrophil adhesion to E3-ICAM was limited by both the contact duration and the tensile stress. We conclude that at low shear, neutrophil adhesion is modulated independently through either LFA-1 or Mac-1, which initially contribute with equal efficiency, but differ over the duration of chemotactic stimulation.