Aberrant S100 expression in cutaneous malignant fibrous histiocytoma: a potential pitfall in diagnosis.
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Aged↗
Biomedical subjects
B Egan
Publications and source records attributed to B Egan.
The impact of birth weight on the racial disparity of end-stage renal disease.
PURPOSE: Blacks have a high rate of end-stage renal disease (ESRD) and low birthweight (LBW) than whites. LBW has been associated with ESRD. The purpose of this study was to assess impact of LBW on the racial difference in ESRD.METHODS: Patients born in SC after 1950 and diagnosed with ESRD between 1991-1996 were identified from the ESRD registry. Birth weight was compared for 858 black and 372 white patients and 2460 controls matched for age, sex, and race. LBW was defined as birthweight <2500 g.RESULTS: Among patients with ESRD, mean birthweight was lower in blacks than whites (3179 vs 3367 g, p < 0.001). LBW was more common in blacks than whites with ESRD (13.9 vs 7.5%, p = 0.02). The risk ratio for LBW among ESRD patients was 1.4 (95% C.I. 1.1 to 1.8) for blacks and 1.5 (95% C.I. 0.9 to 2.5) for whites. The population attributable risk (PAR) for ESRD due to LBW was greater for blacks than whites (33.6 vs 4.2 per 100,000).CONCLUSIONS: Birthweights were lower and LBW was more common among blacks than whites with ESRD. Moreover, LBW contributed more to the PAR of ESRD in blacks than whites. Thus, LBW may contribute to the greater risk for ESRD in African Americans than Caucasians. This preliminary study indicates that further research on the link between LBW and ESRD could be instructive in understanding the racial health disparities.
Journal Article↗
Bone marrow mobilized with granulocyte colony-stimulating factor in related allogeneic transplant recipients: a study of 29 patients.
We studied whether a short course of granulocyte colony-stimulating factor (G-CSF) administered to normal donors immediately before bone marrow (BM) harvest would shorten time to neutrophil and platelet engraftment in matched related allogeneic BM recipients. Twenty-nine normal donors received 4 consecutive daily subcutaneous injections of G-CSF (median dose, 12.1 microg/kg per day; range, 9.6-15.7 microg/kg per day) immediately before BM harvest. Donors tolerated G-CSF well, with only mild myalgias and arthralgias, and BM was easy to aspirate. The BM harvest contained a median of 5.3 x 10(8) white blood cells (WBCs)/kg (range, 3.1-11.1 x 10(8) WBCs/kg) and 2.5 x 10(6) CD34+ cells per kg (range, 1.5-7.3 x 10(6) CD34+ cells per kg). Median times to neutrophil (18 days [range, 11-30 days] versus 22 days [range, 16-36 days]; P = .05) and platelet (22 days [range, 15-55 days] versus 27 days [range, 18-46 days]; P = .04) engraftment were statistically shorter than those of historical control subjects whose donors had not received G-CSF before BM harvest. However, secondary engraftment-dependent outcomes including red blood cell and platelet transfusions, febrile days, days on antibiotics, days from transplant to hospital discharge, and days in hospital during the first 60 days after transplant were not statistically different from historical control subjects. We conclude that G-CSF administered to normal donors immediately before harvest facilitates BM aspiration, increases the WBC content of the harvest, and hastens neutrophil and platelet engraftment compared with historical control subjects.
Adolescent↗
Vascular compression of the rostral ventrolateral medulla in sympathetic mediated essential hypertension.
The pathophysiological factors of neurogenic or sympathetically mediated essential hypertension are unknown. Neurons close to the surface of the ventrolateral medulla (specifically, in the retro-olivary sulcus [ROS]) are integrally involved in the control of blood pressure by means of efferent connections to presympathetic neurons in the spinal cord. It is hypothesized that vascular contact with the ROS is pathogenically involved in neurogenically mediated hypertension. We evaluated that theory in 20 subjects with uncomplicated stage 1 to stage 2 essential hypertension (EHTN) (18 of whom completed the study). The baseline supine plasma norepinephrine level served as an index of central sympathetic outflow. The response of blood pressure to clonidine was used as a surrogate marker for neurogenically mediated hypertension. We also examined the relationship between those markers and evidence of anatomic abnormalities in the area of the ROS that was provided by magnetic resonance imaging. A vessel contacted the left ROS in 5 of the 18 subjects. Those 5 subjects had higher plasma norepinephrine concentrations than did the 13 subjects without this vascular contact (358+/-46 versus 76+/-43 pg/mL, P<0.001). These 5 subjects also exhibited a significant depressor response to clonidine that tended to be greater than that seen in the 13 subjects without vascular contact (-20.6+/-3.2 versus -13.6+/-9 mm Hg). Both race and baseline mean blood pressure had only an independent effect on the depressor response to clonidine. The findings are consistent with the theory that vascular contact with the left ROS may contribute to neurogenically mediated "essential" hypertension in some patients.
Adult↗
Targeting of tail-anchored proteins to yeast mitochondria in vivo.
Tail-anchored proteins are inserted into intracellular membranes via a C-terminal transmembrane domain. The topology of the protein is such that insertion must occur post-translationally, since the insertion sequence is not available for membrane insertion until after translation of the tail-anchored polypeptide is completed. Here, we show that the targeting information in one such tail-anchored protein, translocase in the outer mitochondrial membrane 22, is contained in a short region flanking the transmembrane domain. An equivalent region is sufficient to specify the localisation of Bcl2 and SNARE proteins to the secretory membranes. We discuss the targeting process for directing members of this protein family to the secretory and mitochondrial membranes in vivo.
Amino Acid Sequence↗
Management and outcome of acute myocardial infarction in older patients in the thrombolytic era.
OBJECTIVE: Acute myocardial infarction (AMI) is an important cause of mortality and morbidity in older patients. The aim of this study was to determine the proportion of unselected admissions with AMI that is older than 75 years and to examine management and outcomes in this group. DESIGN: An historical cohort study of consecutive unselected admissions with AMI identified using the Hospital In Patient Enquiry (HIPE) database and validated according to MONICA criteria for definite or probable AMI. SETTING: An acute cardiac unit in a university teaching hospital/cardiac tertiary referral center. RESULTS: Of 1059 patients, 606 (57%) were older than 65 years and 309 (29.2%) were older than 75 years. Mean age in this group was 80.5 years. Hospital mortality was almost twice as high as in patients younger than 75 years (28% vs 15%, P < .001), and age was an independent predictor of short- and long-term mortality following AMI. Women constituted a significantly higher proportion of older patients. Family history of AMI and cigarette smoking were less prevalent in older patients. Mean cholesterol was lower and comorbidities were higher. Other baseline characteristics, including previous AMI, did not differ. However older patients were less likely to receive thrombolysis (13% vs 36%, P < .001), aspirin (76% vs 86%, P < .01), or beta-blockers (25% vs 51%, P < .001) and were less likely to undergo cardiac catheterization or revascularization. Only 53% were admitted to coronary care. CONCLUSION: Patients more than age 75 comprise almost one-third of patients with AMI and have a poor prognosis. Although age is an independent predictor of mortality following AMI, suboptimal management may contribute to the high mortality in these patients.
Adrenergic beta-Antagonists↗
Managing hypertension in the southeastern United States: applying the guidelines from the Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC VI).
The southeastern United States has the highest occurrence of heart disease and stroke and among the highest rates of congestive heart failure and renal failure in the country. The Consortium for Southeastern Hypertension Control (COSEHC) is cooperating with other organizations in implementing initiatives to reduce morbidity and mortality from hypertension-related conditions in the southeastern United States. This article outlines for clinicians special consideration for implementation of the Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC VI) in the southeastern United States. Clinicians are encouraged to adapt the recommendations of JNC VI to their own patient groups, paying attention to these specific areas: (1) Ensure screening for hypertension in your practice and community. (2) Evaluate all patients for accompanying risk factors and target organ damage. (3) Promote lifestyle management for individual patients and populations for prevention and treatment of hypertension. (4) Set a goal blood pressure for each patient, and monitor progress toward that goal. (5) Recognize that many patients will be candidates for blood pressure goals of <130/85 mm Hg. (6) Pay attention to compelling and special indications such as diabetes, congestive heart failure, and renal dysfunction. (7) Consider combination therapy. (8) Maximize staff contributions to enhance patient adherence. (9) Encourage patient, family, and community activities to promote healthy lifestyles and blood pressure control.
Black or African American↗
Characterization of a rat alveolar macrophage cell line that expresses a functional mannose receptor.
The mannose receptor is a single polypeptide transmembrane glycoprotein expressed on the surface of macrophages that binds and internalizes soluble and particulate ligands. Physiological ligands for this receptor are pathogens, such as mycobacteria, and extracellular acid hydrolases and peroxidases. Expression of the mannose receptor is tightly linked to the functional state of the macrophage: the receptor appears during differentiation, is increased by macrophage deactivating agents, and is reduced in the presence of macrophage activating agents. Studies of the mechanisms underlying these regulatory processes have been hampered by the lack of a stable cell line that expresses a functional and appropriately regulated mannose receptor. In this study we describe expression and modulation of the mannose receptor by the rat alveolar cell line NR8383. Similar amounts of the mannose receptor ligand horseradish peroxidase were internalized by both NR8383 cells and alveolar macrophages. In addition, NR8383 cells expressed immunoreactive mannose receptor protein and mannose receptor mRNA as detected by Northern analysis. Regulation studies showed that mannose receptor expression was regulated at the levels of activity, protein, and mRNA in NR8383 cells similarly to regulation in primary rat macrophages. In addition, NR8383 cells could be successfully transfected with a luciferase reporter gene, providing the transfectable, mannose receptor-positive macrophage cell line. These results support the hypothesis that NR8383 cells potentially represent the best current macrophage cell line for studying various aspects of macrophage function, and are particularly critical in studies of regulation of the mannose receptor, a key receptor in host defense and immune regulation.
Animals↗
Trial of stress reduction for hypertension in older African Americans. II. Sex and risk subgroup analysis.
Our objective was to test the short-term efficacy and feasibility of two stress-reduction approaches for the treatment of hypertension in older African Americans, focusing on subgroup analysis by sex and by high and low risk on six measures of hypertension risk: psychosocial stress, obesity, alcohol use, physical inactivity, dietary sodium-potassium ratio, and a composite measure. The study involved a follow-up subgroup analysis of a 3-month randomized, controlled, single-blind trial conducted in a primary care, inner-city health center. Subjects were 127 African American men and women, aged 55 to 85 years, with diastolic pressure of 90 to 104 mm Hg and systolic pressure less than or equal to 179 mm Hg. Of these, 16 did not complete follow-up blood pressure measurements. Mental and physical stress-reduction approaches-the Transcendental Meditation technique and progressive muscle relaxation, respectively-were compared with a life-style modification education control and with each other. Both systolic and diastolic pressures changed from baseline to follow-up for both sexes and for high and low risk level (defined by median split) on the six measures of hypertension risk. Compared with education control subjects, women practicing the Transcendental Meditation technique showed adjusted declines in systolic (10.4 mm Hg, P < .01) and diastolic (5.9 mm Hg, P < .01) pressures. Men in this treatment group also declined in both systolic (12.7 mm Hg, P < .01) and diastolic (8.1 mm Hg, P < .001) pressures compared with control subjects. Women practicing muscle relaxation did not show a significant decrease compared with control subjects, and men declined significantly in diastolic pressure only (6.2 mm Hg, P < .01). For the measure of psychosocial stress, both the high and low risk subgroups using the Transcendental Meditation technique declined in systolic (high risk, P = .0003; low, P = .06) and diastolic (high risk, P = .001; low, P = .008) pressures compared with control subjects, whereas for muscle relaxation, blood pressure dropped significantly only in the high risk subgroup and only for systolic pressure (P = .03) compared with control subjects. For each of the other five risk measures, Transcendental Meditation subjects in both the high and low risk groups declined significantly in systolic and diastolic pressures compared with control subjects. Effects of stress reduction on blood pressure were found to generalize to both sexes and diverse risk factor subgroups and were significantly greater in the Transcendental Meditation treatment group. These effects (along with high compliance) even in individuals with multiple risk factors for hypertension clearly warrant longer-term investigation in this and other populations.
Aged↗
Doxorubicin and dose-escalated cyclophosphamide with granulocyte colony-stimulating factor for the treatment of hormone-resistant prostate cancer.
PURPOSE: The goals of this study were to define the efficacy and toxicity of doxorubicin and dose-escalated cyclophosphamide (Cy) along with granulocyte colony-stimulating factor (G-CSF) in the treatment of hormone-refractory prostate cancer (HRPC), to determine the maximal-tolerated dose (MTD) of Cy in this regimen, and to evaluate the impact of prior pelvic irradiation (XRT) on MTD and toxicity. PATIENTS AND METHODS: Thirty-five patients were treated every 21 days with fixed-dose doxorubicin (40 mg/m2) and Cy 800 to 2,000 mg/m2 (in a cohort dose-escalation schema) along with G-CSF. RESULTS: Five of 15 patients (33%) with measurable disease obtained an objective response. Sixteen of 35 patients (46%) had a greater than 50% decrease in prostate-specific antigen (PSA) level (95% confidence interval [CI], 28.8% to 63.4%). Ten of 35 patients (28.6%) had a greater than 75% decrease in PSA level. The median survival time was 11 months. The median survival duration of patients with a greater than 50% decrease in PSA level was 23 months, versus a median survival time of 7 months in patients without a PSA response (P = .02). Although 33% of cycles were associated with grade 4 neutropenia, febrile neutropenia occurred in only 7.8% of all cycles. Thrombocytopenia and anemia were rare. Nonhematologic toxicity was minimal. Patients who had received prior pelvic XRT had a lower Cy MTD, but their hematologic toxicity was not appreciably different. CONCLUSION: This is a well-tolerated, active regimen for the treatment of HRPC. Toxicity was not different in patients with prior pelvic XRT, although these patients had a lower MTD.
Adenocarcinoma↗
Relationships among plasma aldosterone, high-density lipoprotein cholesterol, and insulin in humans.
To investigate the pathogenesis of hypertension in patients with obesity and insulin resistance and to explore the role of plasma lipids, we studied 30 subjects at the end of 7 days of low (20 mEq/d) then high (200 mEq/d) sodium diets. Glucose and insulin tolerance tests were performed at the end of each week and blood and urine collected for measurements of plasma aldosterone, renin activity, electrolytes, insulin, and lipoproteins. There was a strong negative correlation between plasma aldosterone and high-density lipoprotein cholesterol during both diets. There were weaker positive correlations between plasma aldosterone and insulin or triglycerides. When the aldosterone-renin ratio was the dependent variable and the correlation controlled for serum potassium, the inverse relationship with high-density lipoprotein cholesterol and the positive correlation with insulin remained, but only during the high salt diet. Subjects were divided into three groups based on high-density lipoprotein cholesterol. Subjects with the lowest high-density lipoprotein cholesterol levels showed the highest aldosterone, plasma triglycerides, body mass index, and waist-to-hip ratio. Those subjects also demonstrated the greatest resistance to insulin action on glucose and plasma unesterified fatty acids. There was a weak direct correlation between plasma aldosterone and systolic blood pressure during the high salt diet. These data suggest that high aldosterone levels may be a link between dyslipidemia, insulin resistance, and hypertension, a relationship made more evident by high salt intake.
Adult↗
Effect of circulating epinephrine on platelet function and hematocrit.
We investigated the effect of raising arterial plasma epinephrine within the lower pathophysiological concentration range on various indicators of blood platelet function and hematocrit. Epinephrine was raised over 60 minutes by a stepwise increasing intravenous infusion in 40 healthy men aged 20 to 40 years. Platelet count increased progressively with increasing arterial epinephrine to a maximal change of 69 +/- 6 x 10(9)/L in EDTA-anticoagulated blood and a maximal change of 42 +/- 6 x 10(9)/L in acid-citrate-dextrose (ACD)-anticoagulated blood, and the weight of circulating platelets increased by 29% (P < .001). Platelet size increased significantly in EDTA and decreased in ACD, and the difference between EDTA and ACD was significant (P < .0001) for both count and size, suggesting that epinephrine not only recruits platelets into the circulation but also induces some microaggregation in vivo or adhesion ex vivo. Aggregation of platelets in vitro induced by epinephrine decreased (P < .003 for delta optical density and P = .038 for maximal optical density) after epinephrine infusion compared with saline but did not change when stimulated with ADP or collagen. These findings suggest a selective downregulation of the epinephrine-activating mechanisms concomitant with a rise in the platelet content of epinephrine by 81% (P < .001) and no change in the platelet sodium-proton membrane exchange. The release of granular content (beta-thromboglobulin and platelet factor 4) to the circulation in response to epinephrine was not significant. Thus, under acute conditions it seems that the platelets may protect themselves against inappropriate overstimulation by epinephrine. The importance of platelet epinephrine uptake is still unknown, but sodium-proton exchange does not seem to be involved in regulating the effects of circulating epinephrine on platelet function. Epinephrine has a pronounced effect on raising hematocrit (maximal change of 1.74 +/- 0.13 x 10(-2), P < .0001).
Adult↗
Cardiovascular risk factors, clustering and complications in overweight young men.
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Adult↗
Interpreting the medical culture.
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Australia↗
Importance of overweight in studies of left ventricular hypertrophy and diastolic function in mild systemic hypertension.
The relations of Metropolitan Life Insurance Co. Relative Weight values and blood pressure (BP) to minimal forearm vascular resistance, ventricular septal and posterior wall thickness, left ventricular (LV) mass index and cardiac diastolic function were assessed in 31 men, 37 +/- 2 (mean +/- standard error of the mean) years of age. Eighteen patients with untreated mild hypertension were compared with 13 normotensive control subjects of similar age and weight. The hypertensives had higher clinic (137 +/- 3/96 +/- 2 vs 121 +/- 4/81 +/- 3 mm Hg, p less than 0.001/less than 0.001) and home (p less than 0.001) BP. Despite higher BP, the hypertensives did not have significantly greater values than normotensives, respectively, for minimal forearm vascular resistance (2.20 +/- 0.12 vs 2.04 +/- 0.11 U), ventricular septal (9.9 +/- 0.5 vs 10.2 +/- 0.3 mm) and posterior wall thickness (10.2 +/- 0.4 vs 10.0 +/- 0.3 mm) or LV mass index (106 +/- 6 vs 107 +/- 6 g/m2). Furthermore, diastolic peak filling rate, an index of LV diastolic function, was virtually identical in the 2 groups (2.71 +/- 0.14 vs 2.69 +/- 0.07 liters/s, difference not significant). Correlates of peak filling rate included relative weight (r = -0.62, p less than 0.001), posterior wall thickness (r = -0.51, p less than 0.01) and age (r = -0.45, p less than 0.05). Relative weight also correlated significantly with posterior wall (r = 0.59, p less than 0.005), ventricular septal (r = 0.47, p less than 0.005) and LV mass index (r = 0.38, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
The importance of hemodynamic considerations in essential hypertension.
Hypertension is a major risk factor for cardiovascular morbidity and mortality. Antihypertensive therapy consistently reduces complications from stroke and congestive heart failure, whereas benefits from the treatment of ischemic heart disease events are variable. Several plausible explanations, including hemodynamic hypotheses, have been put forth to account for the failure of treatment to more favorably influence mortality from ischemic heart disease. The effect of hypertension on coronary heart disease is probably much more complex than a simple elevation of arterial pressure. Some of these complexities include the potential separate risks of high total peripheral resistance, high cardiac output, increased myocardial power that reflects pressure times flow, and several structural and functional vascular changes. These factors may act in concert to unfavorably alter the balance between myocardial oxygen supply and demand. Several of these factors will be highlighted in an attempt to offer alternative or adjunctive pathophysiologic examinations for the high-risk subgroups of obesity and the failure of antihypertensive therapy to normalize the rate of coronary heart disease events.
Blood Pressure↗
Effects of ketanserin on blood pressure and platelet aggregation in elderly men with mild hypertension.
Thirteen men, age 60 +/- 2 years (mean +/- SEM) with mild hypertension, 151 +/- 4/95 +/- 3 mm Hg, completed a randomized, double-blind, placebo-controlled crossover trial of ketanserin therapy. In comparison to placebo, ketanserin treatment at 40 mg bid for 6 weeks lowered systolic and diastolic blood pressure, 148 +/- 4/92 +/- 3 vs. 140 +/- 6/86 +/- 3 mm Hg, P = 0.19/0.02. The rate of platelet aggregation in response to ADP and epinephrine was unchanged while the response to serotonin was greatly diminished. Neither the systemic pressor response nor the pupillary mydriatic response to phenylephrine was significantly altered. Plasma norepinephrine concentration declined significantly. Ketanserin reduced blood pressure, particularly the diastolic component, in elderly men with mild hypertension. While antagonism of serotonin's effects on platelet aggregation was evident, blockade of alpha 1-receptor-mediated events was not apparent. The results suggest that during chronic therapy the antihypertensive effects of ketanserin were mediated by serotonergic blockade and a possible lytic effect on sympathetic drive. The dual effects of ketanserin on blood pressure and platelet aggregation may be beneficial in reducing cardiovascular complications in hypertensive patients.
Adult↗
Specialization, surgery, and the Sydney Bulletin.
The development of specialization in Australian medicine in the late 19th and early 20th centuries was not welcomed by all practitioners. Nor was the separation of a class of credentialled surgeons welcomed. The founders of the Royal Australasian College of Surgeons met opposition from many medical quarters, some of which found an unexpected amplifier in the Sydney Bulletin.
Attitude of Health Personnel↗