bluuebunny/crossref_metadata_2025 huggingface dataset:
Various Clinical Manifestations in Patients with Thrombotic Microangiopathy
Authors: Chang Jae C , Kathula Satheesh K
Published: August 2007

Background

Thrombotic microangiopathy (TM) is characterized by thrombocytopenia and microangiopathic hemolytic anemia in association with diffuse microthrombi in the arteriolar capillaries of various organs. Its clinical manifestation is protean, and a few well-defined clinical syndromes have been recognized. A clear understanding of the consequence of TM is needed to appreciate the unusual clinical syndromes due to atypical presentation of thrombotic thrombocytopenic purpura (TTP).

Methods

The medical records of patients with known diagnoses of TTP, hemolytic uremic syndrome (HUS), and the syndrome in which hemolysis, elevated liver enzymes, and low platelet count are found in association with pregnancy were examined retrospectively from 1981 to 1994 and prospectively from 1995 to 2000. Various thrombotic microangiopathic presentations were identified in these patients. Their response to exchange plasmapheresis was evaluated, and their clinical outcome was determined.

Results

A total of 74 patients were diagnosed with TM. Among these patients, several well-defined thrombotic microangiopathic presentations were identified. These presentations included TTP in 57 patients, acute respiratory distress syndrome (ARDS) in 13 patients, HUS in 9 patients, the syndrome in which hemolysis, elevated liver enzymes, and low platelet count are found in association with pregnancy in 9 patients, peripheral digit ischemic syndrome (PDIS) in 6 patients, pancreatitis in 3 patients, hepatitis in 3 patients, and nonocclusive mesenteric ischemia (NOMI) in 2 patients. Exchange plasmapheresis was an effective treatment, with a response rate of 79%. A poor prognosis was evident when ARDS was present, with an overall survival rate of 46%.

Conclusion

Traditionally, TTP and HUS are considered the main entities of TM. It is evident that other manifestations of TM, if unrecognized in a timely fashion, can lead to fatality. The understanding of the pathophysiologic consequences of TM and the recognition of its atypical presentations are essential to achieve favorable outcomes in patients with this life-threatening disease.
Endothelial Dysfunction in Patients with Coronary Artery Disease: A Comparison of Three Frequently Reported Tests
Authors: Monnink Stefan H. J. , Van Haelst Paul L. , Van Boven Ad J. , Stroes Erik S. G. , Tio René A. , Plokker Thijs W. M. , Smit Andries J. , Veeger Nic J. G. M. , Crijns Harry J. G. M. , Van Gilst Wiek H.
Published: August 2007

Background

Endothelial dysfunction is useful in predicting future cardiovascular disease. At present several tests are available to test endothelial function: coronary diameter response to acetylcholine, forearm bloodflow (FBF) response to acetylcholine, and brachial artery flow-mediated dilative (FMD) response to postischemic hyperemia. This study aimed to compare the three most frequently reported endothelial function tests.

Methods

Twenty-eight patients (19 males and nine females, mean age 57 years) referred for diagnostic coronary angiography were considered for endothelial function measurement in the coronary artery as well as in the forearm by FBF and FMD.

Results

Acetylcholine decreased the mean coronary diameter by 7.4% (SD 6.3%) and increased the mean FBF by 230% (SD 152%). Hyperemia increased the mean brachial diameter by 6.7% (SD 4.8%). The effect of acetylcholine on forearm resistance vessels was significantly related to the effect of acetylcholine on the coronary conduit vessels ( P=0.039). Nonetheless, FMD was not related to FBF nor to the coronary response.

Conclusion

In patients with mild coronary endothelial dysfunction, forearm vasoreactivity is related to the coronary response, provided that the same stimulus is used.
Effects of Enhanced External Counterpulsation on Health-Related Quality of Life Continue 12 Months after Treatment: A Substudy of the Multicenter Study of Enhanced External Counterpulsation
Authors: Arora Rohit R. , Chou Tony M. , Jain Diwakar , Fleishman Bruce , Crawford Lawrence , McKiernan Thomas , Nesto Richard , Ferrans Carol Estwing , Keller Susan
Published: August 2007

Background

The Multicenter Study of Enhanced External Counterpulsation (MUST-EECP) was the first prospective, randomized, blinded, sham-controlled study of enhanced external counterpulsation (EECP) in the treatment of chronic stable angina. We previously reported that EECP therapy lengthens the time to exercise-induced myocardial ischemia and reduces angina. We now describe the effects of EECP therapy versus a sham-treated control group in terms of patients’ functioning, their senses of well-being and other Health-Related Quality Of Life (HQOL) parameters from baseline to end of treatment and from baseline to 12 months after treatment.

Objective

To determine whether a 35-hour course of EECP affects the HQOL of patients with symptomatic coronary artery disease, 12 months following treatment.

Methods

Seventy-one of the 139 patients enrolled in MUST-EECP provided evaluable patient-completed questionnaires at baseline, at the end of treatment, and 12 months post-treatment. The Medical Outcomes Study 36-Item Short-Form Health Survey and the Quality of Life Index-Cardiac Version III were used to assess effects on HQOL.

Results

Both groups had similar HQOL scores at baseline. At end of treatment and at 12-month follow up, patients who had active-CP reported greater improvement than those who had inactive-CP in all nine quality of life scales, including ability to perform activities of daily living, ability to work, bodily pain, confidence in health, energy, ability to engage in social activities with family and friends, anxiety and depression, and quality of life issues from the effects of angina on health and functioning. Despite small sample sizes, active-CP patients demonstrated significantly greater improvement at 12 months following treatment in bodily pain, social functioning, and quality of life specific to cardiac patients compared with inactive-CP patients.

Conclusion

Significant health-related quality of life improvements were measurable up to 12 months after the completion of treatment with EECP. Improvements in this controlled study are consistent with HQOL changes reported in case series and patient registries. Larger studies are warranted.
External Bioenergy Increases Intracellular Free Calcium Concentration and Reduces Cellular Response to Heat Stress
Authors: Kiang Juliann G. , Marotta Diane , Wirkus Mietek , Wirkus Margaret , Jonas Wayne B.
Published: August 2007

Background

External bioenergy (energy emitted from the body) can influence a variety of biological activities. It has been shown to enhance immunity, promote normal cell proliferation, increase tumor cell death, and accelerate bone fracture recovery. In this study, we investigated whether external bioenergy could alter intracellular calcium concentration ([Ca2+]i, an important factor in signal transduction) and regulate the cellular response to heat stress in cultured human lymphoid Jurkat T cells.

Methods

A practitioner emitted bioenergy toward tubes of cultured Jurkat cells for one 15-minute period. [Ca2+]i was measured spectrofluorometrically using the fluorescent probe indo-1. The heat shock protein 72 kd was detected using35 S-methionine prepulse and Western blot analysis.

Results

The resting [Ca2+]i in Jurkat T cells was 90±3 nM in the presence of external calcium. The removal of external calcium decreased the resting [Ca2+]i to 54±2 nM, indicating that Ca2+ entry from the external source is important for maintaining the basal level of [Ca2+]i. In the presence of external Ca2+, treatment of Jurkat T cells with external bioenergy for 15 minutes increased [Ca2+]i by 22±3%. [Ca2+]i remained elevated in these cells for 2 hours. Surprisingly, we also observed that [Ca2+]i increased by 11±1% if cells were simply placed in the area where external bioenergy had been used. This lingering effect of external bioenergy dissipated within 24 hours. Treatment with external bioenergy reduced cellular responses to heat stress and did not induce the production of heat shock protein 72 kd, which is known to provide cytoprotection.

Conclusions

These results suggest that externally applied bioenergy can upregulate [Ca2+]i and downregulate the cellular response to stress. The association between the external bioenergy and increases in [Ca2+]i may be a good index for detecting presence of bioenergy.
Protein Kinase C-α Mediates Cigarette Smoke Extract- and Complement Factor 5a-Stimulated Interleukin-8 Release in Human Bronchial Epithelial Cells
Authors: Kashyap Ravindra , Floreani Anthony A. , Heires Arthur J. , Sanderson Sam D. , Wyatt Todd A.
Published: August 2007

Background

Cigarette smoke extract (CSE) activates protein kinase C (PKC) and augments complement factor 5a (C5a)-stimulated release of the proinflammatory cytokine IL-8 in human bronchial epithelial cells (HBEC). We hypothesized that PKC activation by alternative PKC activators will also mediate C5a-stimulated IL-8 release in HBEC.

Methods

HBEC were treated with phorbol myristate acetate (100 ng/mL), calcium ionophore A23187 (2 nM), or 10 nM cholesterol-3-sulfate in the presence or absence of C5a. Interleukin-8 (IL-8) release was measured by enzyme-linked immunoadsorbent assay.

Results

IL-8 release by PKC activators alone was significantly higher than in unstimulated cells and was further augmented in the presence of C5a. Preincubation with the PKC inhibitor calphostin C (1 μM) significantly suppressed IL-8 release in HBEC treated with CSE and C5a. Preincubation with 10 μM TMB-8 (an intracellular calcium sequester) also significantly suppressed IL-8 release in CSE- and C5a-treated HBEC, suggesting that intracellular calcium is required for CSE- and C5a-mediated IL-8 release. When HBEC were preincubated with 30 nM of the PKCβ-specific inhibitor LY363196, CSE- and C5a-mediated IL-8 release was not inhibited. However, with higher concentrations of LY363196 (>600 nM), which exceeds the IC50 for PKCβ greater than 100 fold, CSE- and C5a-mediated IL-8 release was significantly suppressed. Preincubation of HBEC with 100 nM of Gö 6976, a specific PKCα inhibitor, significantly inhibited CSE- and C5a-mediated stimulation of IL-8 release.

Conclusions

Collectively, these data suggest that PKC activators in addition to CSE augment C5a-stimulated IL-8 release from HBEC and that CSE and C5a stimulate IL-8 release in HBEC by activating the calcium-dependent PKCα isoform.
Recombinant Plasma Gelsolin Diminishes the Acute Inflammatory Response to Hyperoxia in Mice
Authors: Christofidou-Solomidou Melpo , Scherpereel Arnaud , Solomides Charalambos C , Christie Jason D , Stossel Thomas P , Goelz Susan , DiNubile Mark J
Published: August 2007

Background

The acute respiratory distress syndrome remains a common and poorly understood complication of a variety of insults. Ventilation with high concentrations of inspired oxygen may further damage already compromised lungs. By scavenging extracellular actin and modulating the effects of lysophosphatidic acid, plasma gelsolin could serve a critical protective role against oxidant injury.

Methods

Mice exposed to >95% O2 for a total of 72 hours were treated with gelsolin or albumin after 24 and 48 hours.

Results

Neutrophil counts in bronchoalveolar fluid rose ( P=0.0002) and gelsolin levels dropped ( P<0.00001) in mice with acute hyperoxic lung injury. The acute inflammatory response to hyperoxia was significantly reduced in the gelsolin-compared with the bovine serum albumin-treated mice ( P=0.03).

Conclusions

These data imply that i) gelsolin depletion contributes to the pathogenesis of oxygen toxicity and ii) repletion of gelsolin can partially abrogate the resultant exudative response.
Differing Effects of Inotropic Agents on Length Change Deactivation of Isolated Rat Myocardium
Authors: Leach John K. , Ford Lincoln E. , Perea John M. , Grimes Laura A. , Skipper Betty J.
Published: August 2007

Background

A rapid change in length of cardiac muscle during isometric contraction is followed by developed force that is less than appropriate for the new length because of deactivation of the contractile system. Length change deactivation may have favorable or unfavorable effects on cardiac function, depending on the circumstances under which it is produced.

Methods

Left ventricular papillary muscles from male Sprague-Dawley rats were arranged for recording of isometric force. After each control or reference isometric contraction, a quick release-quick stretch V-step was applied to the following contraction. For each repetition of control and experimental contractions, the time of application of V-steps was increased by 20 ms until peak force was reached. Effects of these V-steps were assessed from ratios of peak redeveloped force to peak force in an isometric reference contraction. Slopes of plots of these ratios versus time after the onset of the contraction were used to quantify the effects of inotropic agents on deactivation.

Results

Increasing calcium from 2.5 to 5.0 or 7.5 mM increased force by 12±4% (mean±SEM), did not change time to peak, and did not significantly alter the deactivation slope. Adding 5 mM epinephrine increased force by 16±5%, decreased time to peak by 34±3%, and increased the deactivation slope by 106±9% ( P<0.001). Caffeine had variable effects on peak force, increased time to peak by 47±4%, and decreased the deactivation slope by 71±5% ( P<0.001).

Conclusions

The quantitatively different effects of the three agents on length change deactivation slopes and time to peak force suggest a common mechanism, probably involving thin-filament cooperativity.
Tumor Necrosis Factor-α -308 Gene Polymorphism is Associated with Synthetic Hemodialysis Graft Failure
Authors: Ram Sunanda , Bass Kristen , Abreo Ken , Baier John R. , Kruger Thomas E.
Published: August 2007

Background

Progressive venous stenosis mediated, in part, by inflammatory cytokines is a major cause of synthetic hemodialysis graft failure. A tumor necrosis factor-α (TNF-α) gene polymorphism (G to A, position -308) has been shown to increase plasma cytokine levels and severity of diseases with an underlying inflammatory component.

Methods

We genotyped 67 patients with synthetic polytetrafluoroethylene (PTFE) grafts and examined the association of the high- (AA or GA) and low- (GG) production TNF-α -308 genotypes with the rate of graft failures/thrombosis and graft survival.

Results

Hemodialysis patients with the high-production TNF-α genotypes had a significantly increased rate of PTFE graft failure at 90 days (37.2% versus 14%) and 1 year (62.8% versus 34.4%) after graft placement compared with patients with the low-production genotype (respectively). Hemodialysis patients with the high-production TNF-α genotypes had significantly lower cumulative PTFE graft survival at 1 year (29.4% ± 11.1% versus 71.2 ± 6.8%) and 2 years (22.1% ± 10.5% versus 48.2 ± 8.1%) compared with patients with the low-production genotype (respectively). Patients with the A allele had approximately twice the mean thrombosis rate compared with those who had the low-production TNF-α genotype (3.3 ± 0.8 versus 1.7 ± 0.4 thromboses/patient/year, respectively; mean ± SEM, p < .05).

Conclusions

These data suggest that the TNF-α -308 A allele is associated with increased PTFE graft thrombosis and failure in hemodialysis patients.
Utility of Hepatic Phosphorus-31 Magnetic Resonance Spectroscopy in a Rat Model of Acute Liver Failure
Authors: Corbin Ian R. , Buist Richard , Peeling Jim , Zhang Manna , Uhanova Julia , Minuk Gerald Y.
Published: August 2007

The ability to document the extent of hepatic injury and predict the outcome of fulminant hepatic failure would be helpful in identifying those patients who might benefit from liver transplantation. The aim of the present study was to determine whether in vivo phosphorus-31 magnetic resonance spectroscopy (31P MRS) accurately assesses the severity of liver damage and is of prognostic value in a D-galactosamine (D-galN)-induced model of acute liver failure. Adult male Sprague-Dawley rats ( n = 36) received an intraperitoneal dose of D-galN (1.0 g/kg), and MRS examinations were performed at peak (48 hours) and in subsequent experiments, just prior to peak (30 hours) hepatic injury. Rats not exposed to D-galN served as controls. The concentration of hepatic phosphorylated metabolites decreased in proportion to the severity of liver injury at 48 hours. Significant correlations were detected between hepatic adenosine triphosphate (ATP) and serum aspartate aminotransferase, bilirubin, and percentage of hepatocyte necrosis identified histologically ( r = -.91, -.74, and -.92, respectively; p < .001). Prior to peak hepatic injury (30 hours), 31P MRS was able to predict with 100% accuracy those rats that would survive (ATP > 2.3 mM) and those that would not (ATP < 1.5 mM). When an intermediate cutoff value of 2.0 mM was selected, ATP levels were able to correctly predict survival and death with 80% and 60% accuracy, respectively. These findings indicate that hepatic ATP levels as measured by 31P MRS provide a noninvasive indication of the severity of liver damage and serve as a useful prognostic indicator of outcome in this model of acute liver failure.
Effect of Apolipoprotein E Polymorphism on Serum Uric Acid Levels in Healthy Subjects
Authors: Liberopoulos Evagelos N. , Miltiadous George A. , Athyros Vasilios G. , Ganotakis Manolis , Cariolou Marios , Bairaktari Eleni , Elisaf Moses S.
Published: August 2007

Background

We have previously shown that apolipoprotein E (apo E-) polymorphism may affect serum creatinine concentration and predicted glomerular filtration rate in healthy individuals. On the other hand, there are limited data regarding the possible influence of apo E- polymorphism on serum uric acid (SUA) levels.

Methods

Two hundred ninety (148 male, 142 female) apparently healthy white individuals were studied. apo E- genotypes, serum lipid parameters including apolipoproteins, insulin resistance using the homeostasis model assessment (HOMA) as a marker, serum and urine creatinine levels, and serum and urine uric acid concentration were determined in all participants.

Results

The apo E-2 allele was associated with lower serum levels of total cholesterol, higher levels of triglycerides and apo E-, and increased serum creatinine concentration compared with the apo E-3 and apo E-4 alleles in our population. Furthermore, the apo E-2 allele was associated with higher SUA levels (321.3 ± 101.1 μmol/L [5.4 ± 1.7 mg/dL]) compared with the apo E-3 allele (261.8 ± 89.2 μmol/L [4.4 ± 1.5 mg/dL]; p = .012) and the apo E-4 allele (243.9 ± 65.4 μmol/L [4.1 ± 1.1 mg/dL]; p = .010), whereas the apo E-2 allele was associated with a nonsignificant decrease in the fractional renal excretion of uric acid (FEUA) compared with the apo E-3 and apo E-4 alleles (7.9 ± 2.2% vs 8.7 ± 4.2% vs 8.9 ± 5.1%, respectively; p = .53). These observations remained statistically significant when the effect of apo E- polymorphism on SUA levels was adjusted for gender, age, systolic and diastolic blood pressure, body mass index, serum creatinine, and triglyceride and apo E- levels, as well as for HOMA index and FEUA.

Conclusions

Our data provide evidence, for the first time, that the apo E-2 allele is independently associated with increased SUA levels in healthy individuals.
Survey of the Impact of National Institutes of Health Clinical Research Curriculum Awards (K30) between 1999 and 2004
Authors: Bakken Lori L. , Lichtenstein Michael ,   ACRTPD Evaluation Committee
Published: August 2007

Background

This report summarizes a survey conducted in 2004 by the Association of Clinical Research Training Program Directors’ Evaluation Committee. The purpose of this survey was to determine the early capacity of the 59 National Institutes of Health (NIH) K30 programs (funded between 1999 and 2004) to produce clinical investigators trained in core skills required in clinical research.

Methods

In July 2004, a 37-item Web-based survey was distributed to institutions funded by the NIH K30 award mechanism. Frequencies and proportions were computed for each categorical response, and means were calculated for nominal responses using SPSS, version 11.5 (SPSS, Chicago, IL). Items 7 (funding year) and 8 (recruitment year) were cross-tabulated to ascertain the tempo at which programs were able to establish their enrolment processes.

Results

Forty-five of the 59 programs funded by the K30 award (76%) responded to this survey. The average number of active trainees in each program is 32. Women constitute 53% of active trainees, and 22% of them are underrepresented minorities. Ninety-six percent of active trainees have medical degrees. The average number of graduates over the 5-year funding period is 18. Of the graduates, 50% are women and 17% are underrepresented minorities. Fifty-six percent of them earned certificates, 44% earned master of science degrees, and 13% earned other degrees. Sixty-one percent of K30 program graduates have some extramural funding to support their research. The average number of publications per trainee for all trainees (active and graduate) is 2.3.

Conclusion

The K30 program has been a catalyst at multiple US institutions for improving the pedagogy for clinical research training. It has successfully fulfilled the mandate set forth by the 1998 NIH Director's Panel on Clinical Research (Nathan Report).
Insulin-Like Growth Factor I-Mediated Skeletal Muscle Hypertrophy is Characterized by Increased mTOR-p70S6K Signaling without Increased Akt Phosphorylation
Authors: Song Yao-Hua , Godard Michael , Li Yangxin , Richmond Scott R. , Rosenthal Nadia , Delafontaine Patrick
Published: August 2007

Background

Insulin-like growth factor I (IGF-I) is an anabolic hormone that is known to induce skeletal muscle hypertrophy. However, the signaling pathways mediating IGF-I's hypertrophic effect in vivo are unknown.

Method

The phosphorylation of 46 proteins was investigated by Kinetworks proteomic analysis in the gastrocnemius muscle of transgenic mice overexpressing IGF-I myosin light chain/muscle specific IGF-I (MLC/mIgf-I) and wild-type littermates.

Results

In the hypertrophic muscle of MLC/mIgf-I mice, we observed increased phosphorylation of phosphoinositide-dependent protein kinase 1 (PDK1; 53% increase), the mammalian target of rapamycin (mTOR; 112% increase), and p70 S6 kinase (p70S6K) (254% increase) but no significant change in Akt phosphorylation (4% decrease). Furthermore, we found reduced phosphorylation of MAP kinase kinase 1 and 2 (MEK1/2) (60% decrease) and of mitogen-activated protein kinase kinases 3 and 6 (MKK3/6) (50% decrease) in muscle from transgenic mice, suggesting that the hypertrophic and mitogenic effects of IGF-I are mediated via distinct signaling pathways in skeletal muscle and that inhibition of the mitogen-activated protein (MAP) kinase pathway may be required for the IGF-I-induced hypertrophic effect. Single-fiber analysis revealed a trend toward a higher percentage of the fast twitch fibers (IIb and IIx) in the transgenic mice.

Conclusion

Persistent overexpression of IGF-I in mice skeletal muscle results in hypertrophy, which is likely mediated via the mTOR/p70S6K pathway, potentially via an Akt-independent signaling pathway.
Exercise, Caloric Restriction, and Systemic Oxidative Stress
Authors: Galassetti Pietro R. , Nemet Dan , Pescatello Andria , Rose-Gottron Christie , Larson Jennifer , Cooper Dan M.
Published: August 2007

Background

In humans, the main sources of reactive oxygen species (ROS), the molecules causing oxidative stress, are mitochondrial superoxide ions and neutrophil-derived oxidative radicals. Circulating antioxidants contribute to the protection against oxidative stress. Although the formation of ROS and secretion of antioxidants are independently regulated by exercise and diet, little is known about their combined effect. We hypothesized that relatively brief, intense exercise training may reduce systemic oxidation via an intrinsic mechanism, independent of changes in circulating antioxidants and of neutrophil-derived enzymes (as may be caused by concomitant caloric restriction).

Methods

Nineteen volunteers exercised for 7 days, 3 hours/day at 75% of oxygen uptake. Caloric intake was either 110% of caloric expenditure (high calorie, n = 10) or 75% of caloric expenditure (low calorie, n = 9). Blood samples for F2-isoprostanes, catalase, myeloperoxidase (MPO), interleukin-x (IL-x), white blood cells (WBCs), and other metabolic variables were taken at baseline, at the end of training, and 1 week after completion of the study.

Results

Serum F2-isoprostanes (μg/mL), markers of lipid peroxidation, were similarly reduced after 7 days of exercise in the high-calorie (from 35 ± 4 to 27 ± 2) and low-calorie (from 35 ± 3 to 24 ± 2) groups. Similar reductions were observed in IL-x concentrations. Conversely, no change was observed in circulating concentrations of the antioxidant catalase. Whereas total WBCs and neutrophil counts were significantly reduced in the low-calorie group only, no difference in neutrophil-derived MPO was measured between groups.

Conclusion

A significant reduction in systemic oxidation may occur relatively early during intense exercise training in healthy young men, independent of caloric intake. The potential contribution to these effects of circulating antioxidants and neutrophil-derived oxidative enzymes will require further investigation.
Differences in Triage Thresholds for Patients Presenting with Possible Acute Coronary Syndromes: More than Meets the Eye
Authors: Milch Catherine E. , Kent David M. , Ruthazer Robin , Pope Hector J. , Aufderheide Thomas P. , McNutt Robert A. , Selker Harry P.
Published: August 2007

Background

Many studies have shown differences in cardiac care by racial/ethnic groups without accounting for institutional factors at the location of care.

Objective

Exploratory analysis of the effect of hospital funding status (public vs private) on emergency department (ED) triage decision making for patients with symptoms suggestive of acute coronary syndromes (ACSs) and on the likelihood of ED discharge for patients with confirmed ACS.

Study Design and Setting

Secondary analysis of data from a randomized controlled trial of 10,659 ED patients with possible ACS in five urban academic public and five private hospitals. The main outcome measures were the sensitivity and specificity of hospital admission for the presence of ACS at public and private hospitals and the adjusted odds of a patient with ACS not being hospitalized at public versus private hospitals.

Results

Of 10,659 ED patients, 1,856 had confirmed ACS. For patients with suspected ACS, triage decisions at private hospitals were considerably more sensitive (99 vs 96%; p < .001) but less specific (30 vs 48%; p < .001) than at public hospitals. The difference between hospital types persisted after adjustment for multiple patient-level and hospital-level characteristics.

Conclusion

Significant differences in triage for patients with suspected ACS exist between public and private hospital EDs, even after adjustment for multiple patient demographic, clinical, and institutional factors. Further studies are needed to clarify the causes of the differences.
Current Science of Regenerative Medicine with Stem Cells
Authors: Prentice David A.
Published: August 2007

Regenerative medicine with stem cells holds great hope for the treatment of degenerative disease. The medical potential of embryonic stem cells remains relatively untapped at this point, and significant scientific hurdles remain to be overcome before these cells might be considered safe and effective for uses in patients. Meanwhile, adult stem cells have begun to show significant capabilities of their own in repair of damaged tissues, in both animal models and early patient trials.
Research Ethics, Science Policy, and Four Contexts for the Stem Cell Debate
Authors: Cameron Nigel M. de S.
Published: August 2007

There are plainly conscientious differences of opinion among scientists, politicians, and the public in respect of both the ethics of embryonic stem cell research and the more general question of the role of public policy in setting parameters for what is legal and what is funded in the biosciences. Although professional discussion of embryonic stem cell research is not hampered by the often misleading oversimplifications of the press, it remains true that the wide range of ethical options is rarely explored. These varied positions arise from a series of at least six logically distinct policy options, which we may summarize in these terms: (a) All use of human embryos for research is wrong. (b) Excess in vitro embryos may be used, but others should not be created for the purpose. (c) In vitro embryos, but not clonal embryos, may be created with the intent of using them for research. (d) Clonal embryos, but not in vitro embryos, may be created with the intent of using them for research. (e) Only certain excess embryos destroyed before a certain date should be used. (f) Only certain excess embryos created before a certain date should be used.

Moreover, in any policy permitting research use of the embryo, two further sets of issues are raised. First is the question of consent. Second is the question of time limits. As advancements in biotechnology shape the possibilities of the twenty-first century and hold out both promise and threat to the human future, it is crucial that we develop a national and global conversation that both encourages science and its potential and takes wider social responsibility for the purposes for which science is engaged.
Molecular Mechanisms Linking Sodium to Hypertension: Report of a Symposium
Authors: Hamilton Bruce P. , Blaustein Mordecai P.
Published: August 2007

There is abundant clinical and epidemiologic data linking excess body sodium with hypertension. The mechanism(s) at the molecular level to explain this relationship are unknown. Recent studies by multiple investigators, have identified several ion transport mechanisms in the vascular wall that interact to control vascular tone and contractility. These new data include 1) biochemical, pharmacologic, and molecule structural studies, 2) experiments in transgenic and knockout mice, and 3) results in clinical hypertension. The overall results provide compelling evidence for the concept that salt-dependent hypertension involves the secretion of endogenous ouabain (EO), an adrenal steroid synthesized with the same initial steps as aldosterone and secreted by the zona glomerulosa. Circulating EO inhibits arterial smooth muscle Na+ pumps with alpha 2 subunits. These are functionally coupled to the type 1 Na/Ca exchanger (NCX1). Thus when a2 Na pumps are inhibited in arterial smooth muscle, the resulting subplasma membrane increase in Na+ concentration triggers, via NCX1 Ca2+ entry, a rise in cytosolic Ca2+ concentration and increased myogenic tone and contractility. The ultimate result is a rise in peripheral vascular resistance—the hemodynamic hallmark of hypertension. The elucidation of this pathway has facilitated the development of pharmacologic agents that have therapeutic potential for hypertension and other cardiovascular diseases. These include agents that compete with EO for binding to the Na+ pump and inhibitors of NCX1.
Hemoglobin Serves to Protect Plasmodium Parasites from Nitric Oxide and Reactive Oxygen Species
Authors: Sobolewski Peter , Gramaglia Irene , Frangos John A. , Intaglietta Marcos , van der Heyde Henri C.
Published: August 2007

Our understanding of how the host immune response kills Plasmodium, the causative agent of malaria, is limited and controversial. One widely held belief is that reactive oxygen species are crucial for controlling parasite replication. One of the hallmarks of blood-stage malaria is the cyclic rupture of erythrocytes by the parasite, which releases free hemoglobin into the circulation. We propose that this free hemoglobin, as well as the hemoglobin within the erythrocyte and surrounding the parasite, effectively shields Plasmodium from reactive oxygen species well in excess of those achievable in vivo.
Impaired Lung Vascular Endothelial Growth Factor in Extremely Premature Baboons Developing Bronchopulmonary Dysplasia/Chronic Lung Disease
Authors: Tambunting Francis , Beharry Kay D. A. , Waltzman Joshua , Modanlou Houchang D.
Published: August 2007

Background

Preterm infants exposed to O2 with mechanical ventilation often develop bronchopulmonary dysplasia (BPD), a form of chronic lung disease (CLD). The pathogenesis of BPD/CLD involves dysmorphic microvasculature and disrupted alveolarization. This may be due to impaired vascular endothelial growth factor (VEGF) and VEGF receptor expression.

Methods

To examine the ontogeny of VEGF and VEGF receptors in baboon lungs from 125 to 185 (term) days gestation and to determine whether exposure to O2 and mechanical ventilation alter these ontogenic profiles, we examined lung specimens from three O2-exposed groups: (1) animals delivered at 125 days gestation and exposed to O2 for 14 days as needed; (2) animals delivered at 140 days gestation and exposed to O2 for 10 days as needed; and (3) animals delivered at 140 days gestation and exposed to 100% O2 for 10 days. Lungs from gestational age-matched controls were also examined at 125, 140, 160, 175, and 185 (term) days.

Results

VEGF189 was the most abundant splice variant in the lungs at all stages of development. Extremely premature baboons developing BPD/CLD had higher lung VEGF121 messenger ribonucleic acid (mRNA) expression. However, transcripts for VEGF189, VEGF165, and VEGF receptors (Fms-like tyrosine kinase-1 [Flt-1], kinase-insert domain receptor [KDR]/fetal liver kinase-1 [Flk-1], and neuropilin 1) were suppressed in the BPD models.

Conclusions

We conclude that impaired VEGF and VEGF receptor mRNA expression in lungs from extremely premature baboons developing BPD/CLD may contribute to dysmorphic microvasculature and disrupted alveolarization.
Patient Knowledge Improves Glycemic Control: Is it Time to Go Back to the Classroom?
Authors: Panja Srinivas , Starr Brian , Colleran Kathleen M.
Published: August 2007

Background

Over the last two decades, pharmaceutical intervention for the treatment of type 2 diabetes has expanded. Studies over this same time demonstrated the benefits of tight glycemic control. Unfortunately, despite the availability of novel therapies, glycemic control remains problematic. Nonpharmacologic interventions need to be explored, including patient empowerment. Improving patient knowledge of diabetes may ultimately improve glycemic control. To test this hypothesis, we compared patients’ diabetes knowledge with their glycemic control.

Methods

The Michigan Diabetes Knowledge Test, designed by the University of Michigan, was administered to patients with type 2 diabetes at three University of New Mexico primary care clinics. Patient records were reviewed. The most recent hemoglobin A1c (HbA1c) value was recorded. The data were analyzed using linear regression analysis.

Results

Seventy-seven patients completed surveys and had HbA1c values available. Only questions 1 to 14 of the 23-question survey were used because they pertained specifically to type 2 diabetes. HbA1c was inversely correlated with the number of questions answered correctly on the test (r = -.337, p < .003). Using “all subsets” regression, a correct response to questions 1, 3, and 9 specifically correlated with a lower HbA1c (p < .0001).

Conclusions

These results demonstrate that an inverse linear relationship exists between performance on this diabetes test and HbA1c values. Improvement in patient knowledge of diabetes and the importance of treatment may indeed improve glycemic control and ultimately decrease complications. Studies aimed at empowering patients with disease knowledge may help control the ramifications of the growing diabetes epidemic.
Effect of Diclofenac on Experimental Pleurodesis Induced by Tetracycline in Rabbits
Authors: Kaya Seyda Ors , Bir Ferda , Atalay Habip , Onem Gokhan , Aytekin Faruk Onder , Saçar Mustafa
Published: August 2007

Background and Objective

Pleurodesis is a frequently preferred procedure in thoracic surgery, and many factors may affect the process. We aimed to determine whether the administration of systemic diclofenac sodium diminishes the effectiveness of the pleurodesis induced by intrapleural tetracycline in rabbits.

Methods

Twelve male New Zealand rabbits that received tetracycline 35 mg/kg intrapleurally were allocated into two groups. The first group (diclofenac group, n = 6) received 2 mg/kg diclofenac sodium intramuscularly for 10 days, and the second group (control group, n = 6) received acetaminophen 30 mg/kg orally for 10 days after the pleurodesis procedure. The rabbits were sacrificed after 28 days, and the pleural spaces were assessed grossly for evidence of pleurodesis and microscopically for evidence of fibrosis, inflammation, and collagenization.

Results

The mean macroscopic pleurodesis score of the diclofenac group was 2.16 ± 0.40 compared with 2.83 ± 0.40 in the control group (p = .027). The mean microscopic pleurodesis score of the diclofenac group was 2. 3 ± 1.03, whereas it was 3.5 ± 0.54 in the control group (p = .045).

Conclusion

The administration of diclofenac sodium for 10 days following tetracycline pleurodesis reduces the effectiveness of pleurodesis in rabbits.
Fleeting Glimpses of Lipid Rafts: How Biophysics is Being used to Track Them
Authors: Kenworthy Anne K.
Published: August 2007

Cell membranes are fluid but can exhibit local order that gives rise to lateral inhomogeneities, often referred to as membrane microdomains. Among the best studied yet least well understood of these microdomains are lipid rafts. Lipid rafts are hypothesized to participate in a variety of physiologic and pathologic pathways important to human health by causing the spatial segregation of proteins and lipids within the plane of the membrane. Despite the widespread implications of the raft model, major questions remain about raft size, composition, and life span. This article discusses how recent biophysical measurements of the dynamic properties of rafts and putative raft-associated proteins and lipids are being used to test the hypothesis that confinement of proteins in rafts slows and/or impairs their ability to sample their microenvironment by lateral diffusion.
Peroxisome Proliferator-Activated Receptor α L162V Polymorphism in Nonalcoholic Steatohepatitis and Genotype 1 Hepatitis C Virus-Related Liver Steatosis
Authors: Verdi Hasibe , Sare Koytak Elif , Önder Oğuz , Arslan Ergül Ayça , Cinar Kubilay , Idilman Ramazan , Erden Esra , Mithat Bozdayi Abdurrahman , Yurdaydin Cihan , Uzunalimoglu Özden , Bozkaya Hakan
Published: August 2007

Background

Peroxisome proliferator-activated receptor α (PPARα) plays important roles in lipid metabolism. A recently discovered L162V polymorphism of the PPARα gene is associated with enhanced transcriptional activity. In this study, the frequency of L162V was investigated in nonalcoholic steatohepatitis (NASH) and genotype 1 hepatitis C virus (HCV)-related liver steatosis.

Methods

Seventy-two NASH and 141 HCV-infected patients (54 with steatosis, 87 without steatosis) and 119 healthy controls were included. L162V polymorphism of the PPARα gene was analyzed by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP).

Results

PCR and RFLP analysis of the related gene segment was successful in 93%, 96%, and 100% of NASH and HCV-infected patients and controls, respectively. The frequency of the L162V polymorphism was similar in the NASH and HCV-infected patients and controls (5.9%, 3.6%, and 2.5%, respectively). No difference in the frequency of this polymorphism was observed in HCV-infected patients with or without significant liver steatosis. L162V was not associated with obesity, type 2 diabetes mellitus, hypercholesterolemia, or hypertriglyceridemia.

Conclusions

Neither NASH nor genotype 1 HCV-related liver steatosis seems to be associated with the PPARα L162V polymorphism. This polymorphism may have no association with the presence of type 2 diabetes mellitus, obesity, or various blood lipid alterations in NASH and HCV-infected patients.
Supportive Programs Increase Medical Students’ Research Interest and Productivity
Authors: Zier Karen , Friedman Erica , Smith Lawrence
Published: August 2007

Background

Advances in biomedical research during the last decade have highlighted the necessity of attracting greater numbers of physicians to careers that include a research component. Physician participation in research is essential to increase the number of clinical and translational studies performed, as well as to educate the public about the importance of clinical trials and to assist in recruiting participants. We hypothesized that attractive research opportunities that included faculty mentoring, recognition of participation, and rewards for accomplishments would encourage medical student participation.

Methods

The Medical Student Research Office was created at Mount Sinai School of Medicine in 1996 to develop structured research programs and advise students looking to undertake a research project. Data from students participating in the summer research program and Medical Student Research Day, from the research section of the Medical Student Performance Evaluation, were collected from 1996 to 2004.

Results

For the last 4 years, the majority of medical students did research following the first year of school. Students did basic and clinical research, although most preferred clinically oriented or translational projects. Participation in Research Day and the number of publications suggest that interest is growing, including that by traditionally underrepresented groups.

Conclusion

Although it is too early to assess the long-term effects, the research programs offered led to greater numbers of students who did research, including those in traditionally underrepresented groups. Moreover, students were highly satisfied with their experiences, with 80% feeling that it increased their interest in applying principles they learned to the practice of medicine.
Proinflammatory Reaction and Cytoskeletal Alterations in Endothelial Cells after Shock Wave Exposure
Authors: Sondén Anders , Johansson Anne-Sofie M. , Palmblad Jan , Kjellström Thomas B.
Published: August 2007

Background

Although the effects on human organs by shock waves (SWs) induced by medical treatments or high-energy trauma are well recognized, little is known about the effects on the cellular level. Since blood vessel injury is a common finding after SW exposure, we assessed the in vitro effects of SWs on human umbilical vein endothelial cells (HUVECs).

Methods

An in vitro trauma model was used to expose HUVEC monolayers to focused SWs or to shock waves plus cavitation (SWC), a subsequent phenomenon that is often considered the main cause of SW vascular injury.

Results

SWs alone did not cause any changes in the studied variables. In contrast, HUVEC monolayers exposed to SWC exhibited discrete central lesions with extensive cell death. Cells peripheral to the main lesion area displayed disassembly of dense peripheral bands and formation of actin stress fibers, indicating increased intercellular gaps. Expression of P-selectin was enhanced 11-fold compared with controls, whereas expression of E-selectin and intercellular adhesion molecule 1 was enhanced 8-fold ( p < .05) and 1.5-fold ( p < .01), respectively. The latter responses were preceded by nuclear translocation of nuclear factor κB subunit p65 by 16% ( p < .01). When compared with mechanically produced lesions used as controls, SWC lesions exhibited an impaired regeneration rate of the endothelial cell layer ( p < .001). Redistribution of centrosomes toward the lesion borders was less effective in the SWC samples compared with the mechanically produced lesions ( p < .01).

Conclusions

SWC lesions were associated with a switch to an endothelial proinflammatory phenotype, with an impaired regeneration rate and changes in cytoskeletal functions.
Does Waiver of Written Informed Consent from the Institutional Review Board Affect Response Rate in a Low-Risk Research Study?
Authors: Krousel-Wood Marie , Muntner Paul , Jannu Ann , Hyre Amanda , Breault Joseph
Published: August 2007

Background

Requiring written informed consent for a minimal-risk survey may result in limited participation rates.

Methods

Data from a cross-sectional survey of 177 older patients (87 blacks and 90 whites) with hypertension enrolled in the managed care Medicare risk product were used to assess participation rates pre- and postwaiver of written informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization. Prior to the waivers being granted, patients were contacted two times via mail with an introductory letter and an informed consent document. Those who completed and returned the informed consent document were administered the questionnaire. After 6 weeks, a waiver of written informed consent and HIPAA authorization was obtained from the Institutional Review Board. Nonparticipants were reapproached and asked to complete the questionnaire. Participation rates were recorded before and after receiving the waivers.

Results

Participation rates increased from 21.5% in the prewaiver period to 57.4% in the postwaiver period ( p < .001). Prewaiver participation differed by demographic subgroup and was higher among whites (26.7%) versus blacks (16.1%; p = .087), men (31.6%) versus women (16.7%; p = .024), and participants ≥ 75 years old (28.4%) versus < 75 years old (14.6%; p = .025). In contrast, the postwaiver participation rate did not differ significantly across race, gender, or age subgroupings. Significant increases in participation rates from the pre- to the postwaiver time period were noted within each demographic subgroup (all p < .01).

Conclusions

We identified a substantial increase in participation rates postwaiver of written informed consent and HIPAA authorization in a minimal-risk survey. The need for written documentation for minimal-risk surveys may negatively impact recruitment of blacks, women, and patients < 75 years old.
Atherosclerosis: Immune and Inflammatory Aspects
Authors: Reiss Allison B. , Glass Amy D.
Published: August 2007

This review article discusses the historical origin of our continuously evolving model of the etiology of atherosclerotic cardiovascular disease. The basic molecular biologic concepts underlying the development of coronary artery disease and the dynamic connection between the immune system and arterial integrity are explored. Emphasis is placed on the role of inflammation as a driving force in the process of atherosclerosis and vascular endothelium as a modulating factor in the pathogenesis of coronary artery disease.