Clinical significance of granulocyte-inhibiting proteins.
Explore the source record for details and available documents.
Cytokines↗
Biomedical subjects
G Cohen
Publications and source records attributed to G Cohen.
Interferon-associated retinopathy in a young, insulin-dependent diabetic patient.
Explore the source record for details and available documents.
Adolescent↗
Soliton interaction with an external traveling wave
The dynamics of soliton pulses in the nonlinear Schrodinger equation (NLSE) driven by an external traveling wave is studied analytically and numerically. The Hamiltonian structure of the system is used to show that, in the adiabatic approximation for a single soliton, the problem is integrable despite the large number of degrees of freedom. Fixed points of the system are found, and their linear stability is investigated. The fixed points correspond to a Doppler shifted resonance between the external wave and the soliton. The structure and topological changes of the phase space of the soliton parameters as functions of the strength of coupling are investigated. A physical derivation of the driven NLSE is given in the context of optical pulse propagation in asymmetric, twin-core optical fibers. The results can be applied to soliton stabilization and amplification.
Journal Article↗
Mutations in the FIE and MEA genes that encode interacting polycomb proteins cause parent-of-origin effects on seed development by distinct mechanisms.
In flowering plants, two cells are fertilized in the haploid female gametophyte. Egg and sperm nuclei fuse to form the embryo. A second sperm nucleus fuses with the central cell nucleus, which replicates to generate the endosperm, a tissue that supports embryo development. The FERTILIZATION-INDEPENDENT ENDOSPERM (FIE) and MEDEA (MEA) genes encode WD and SET domain polycomb proteins, respectively. In the absence of fertilization, a female gametophyte with a loss-of-function fie or mea allele initiates endosperm development without fertilization. fie and mea mutations also cause parent-of-origin effects, in which the wild-type maternal allele is essential and the paternal allele is dispensable for seed viability. Here, we show that FIE and MEA polycomb proteins interact physically, suggesting that the molecular partnership of WD and SET domain polycomb proteins has been conserved during the evolution of flowering plants. The overlapping expression patterns of FIE and MEA are consistent with their suppression of gene transcription and endosperm development in the central cell as well as their control of seed development after fertilization. Although FIE and MEA interact, differences in maternal versus paternal patterns of expression, as well as the effect of a recessive mutation in the DECREASE IN DNA METHYLATION1 (DDM1) gene on mutant allele transmission, indicate that fie and mea mutations cause parent-of-origin effects on seed development by distinct mechanisms.
Arabidopsis↗
Oxidative stress, mitochondrial respiration, and Parkinson's disease.
When either oxidizing species, such as H2O2 or oxy-radicals, are present in excess or cellular anti-oxidant defenses are lowered, a state of oxidative stress exists. Parkinson's disease is characterized by the loss of dopamine (DA) neurons, which leads to overactivity of the surviving DA neurons and an increase in neurotransmitter release and turnover. The increased metabolism of DA neurotransmitter by monoamine oxidase (MAO) can be looked upon as an endogenous oxidative stress, leading to damage to Complex I-linked mitochondrial respiration. It remains an open question to what extent the mitochondrial damage seen in Parkinson's disease is of genetic origin and how much is caused by H2O2 generated during enhanced turnover of DA, especially during treatment with L-dopa.
Animals↗
Randomized controlled trial of supported discharge in patients with exacerbations of chronic obstructive pulmonary disease.
BACKGROUND: A randomised trial was performed on patients presenting to hospital with an exacerbation of chronic obstructive pulmonary disease (COPD) to compare outcomes in those managed at home with support with those admitted to hospital in the standard manner. METHODS: Over an 18 month period all patients presenting to the Royal Infirmary of Edinburgh on weekdays (n=718) with a diagnosis of an exacerbation of COPD were assessed for inclusion in the trial. Patients with impaired level of consciousness, acute confusion, acute changes on radiography, or an arterial pH of <7.35 or with other serious medical or social reasons for admission were excluded. Patients randomised to home support were discharged with an appropriate treatment package (antibiotics, corticosteroids, nebulised bronchodilators and, if necessary, home oxygen). They were visited by a nurse the following day and thereafter at intervals of 2-3 days until recovery when they were discharged from follow up. Parallel observations were made on patients allocated to normal hospital admission up to the point of discharge. Patients in both groups were assessed at home eight weeks after the initial assessment. RESULTS: Among weekday patients 353 (50%) were considered obligatory admissions, 140 (19%) were admitted because of co-morbidity, 17 (2%) because of poor social circumstances, and 24 (3%) did not consent to the trial. The remaining 184 (26%) were randomised (2:1) either to home support or to a standard hospital admission. The median time to discharge was 7 days for the home support group and 5 days for the admitted group (p<0.01); 25% of the home support group and 34% of the admitted group were readmitted before the final assessment at eight weeks (p>0.05). There were no significant differences between the groups in attendances by GPs and carers or in health status measured eight weeks after the initial assessment. Satisfaction with the service was good. The mean total health service cost per patient was estimated as 877 pounds sterling for the home support group and 1753 pounds sterling for the admitted group. CONCLUSIONS: This study shows that home supported discharge is a well tolerated, safe, and economic alternative to hospital admission for a proportion of patients referred to hospital for admission for an exacerbation of COPD.
Adult↗
Optimal myocardial preconditioning in humans.
We developed a model of ischemia and reperfusion (I and R) in human ventricular myocytes (CM). CM injury and metabolics were studied after various interventions: endogenous preconditioning (PC) with anoxia, hypoxia, and anoxic or hypoxic supernatants; endogenous PC with or without SPT or adenosine deaminase; and exogenous adenosine PC before, during, or after I or continuously, with or without SPT. To assess the clinical implications of PC and the possible mediating effects of adenosine, patients undergoing elective coronary bypass surgery (CABG) received either a high or low dose of adenosine. Patients not receiving adenosine served as controls. Adenosine levels, high-energy phosphate levels, the metabolic parameters were evaluated from blood samples and left ventricular biopsy samples. Our cellular model studies indicated that preconditioning conferred protection to human CM via an adenosine-mediated pathway. Adenosine simulated PC without a fall in ATP. Adenosine administered to patients during CABG stimulated myocardial metabolism while preventing the degradation of high energy phosphates. A prospective randomized trial of adenosine administered to high-risk patients for myocardial protection is required.
Adenosine↗
Exploring biomolecular recognition using optical biosensors.
Understanding the basic forces that determine molecular recognition helps to elucidate mechanisms of biological processes and facilitates discovery of innovative biotechnological methods and materials for therapeutics, diagnostics, and separation science. The ability to measure interaction properties of biological macromolecules quantitatively across a wide range of affinity, size, and purity is a growing need of studies aimed at characterizing biomolecular interactions and the structural elements that drive them. Optical biosensors have provided an increasingly impactful technology for such biomolecular interaction analyses. These biosensors record the binding and dissociation of macromolecules in real time by transducing the accumulation of mass of an analyte molecule at the sensor surface coated with ligand molecule into an optical signal. Interactions of analytes and ligands can be analyzed at a microscale and without the need to label either interactant. Sensors enable the detection of bimolecular interaction as well as multimolecular assembly. Most notably, the method is quantitative and kinetic, enabling determination of both steady-state and dynamic parameters of interaction. This article describes the basic methodology of optical biosensors and presents several examples of its use to investigate such biomolecular systems as cytokine growth factor-receptor recognition, coagulation factor assembly, and virus-cell docking.
Artifacts↗
A multicenter, double-blind, randomized comparison of oral ondansetron 8 mg b.i.d., 24 mg q.d., and 32 mg q.d. in the prevention of nausea and vomiting associated with highly emetogenic chemotherapy. S3AA3012 Study Group.
The objectives of this study were to compare the efficacy and safety of orally administered ondansetron 8 mg b.i.d., 24 mg q.d., and 32 mg q.d. in the prevention of nausea and vomiting associated with high-dose cisplatin-based chemotherapy (cisplatin > or = 50 mg/m2). This was a randomized, parallel-group, double-blind study conducted in North America. It was planned that all patients would receive one of the following orally administered ondansetron treatments 30 min before starting cisplatin dosing (administered over < or = 3 h): 8 mg b.i.d. with 8 h between doses (124 patients), 24 mg q.d. (116 patients), and 32 mg q.d. (117 patients). Use of prophylactic corticosteroids was not permitted. During the 24-h study period, the highest complete response rate (no emesis, rescue antiemetic therapy, or withdrawal) occurred in patients who received ondansetron 24 mg q.d.: 76/115 or 66%, as against 68/124 (55%) after ondansetron 8 mg b.i.d. and 64/117 (55%) after ondansetron 32 mg q.d. Complete control of nausea (no nausea, no rescue, no withdrawal) occurred in more patients in the ondansetron 24 mg q.d. group (64/114, 56%) than in the ondansetron 8 mg b.i.d. group (43/121, 36%) or in the ondansetron 32 mg group (55/117, 50%). These results demonstrate that following highly emetogenic cisplatin-based chemotherapy (> or =2 50 mg/m2), oral ondansetron 24 mg q.d. is more effective than 8 mg b.i.d. for overall control of nausea, and at least as effective if not more effective in the control of acute vomiting than 8 mg b.i.d. or 32 mg q.d. Ondansetron 24 mg q.d. was well tolerated, and no new or unexpected adverse events were identified.
Administration, Oral↗
Should the pericardium be closed routinely after heart operations?
BACKGROUND: Repeat coronary artery bypass grafting is more difficult if the right ventricle is firmly attached to the inner table of the sternum. Closure of the pericardium at the time of the initial procedure may prevent attachment of the right ventricle to the sternum. This study attempts to identify the geometric effects of pericardial closure early after isolated coronary artery bypass grafting. METHODS: Forty-two patients undergoing elective, isolated coronary artery bypass grafting were randomized into two groups: 20 patients underwent closure of the pericardium (Closure group) and the pericardium was left open in 22 patients (Open group). Radiopaque markers were attached to the anterior aspect of the right ventricular epicardium in both groups. RESULTS: Postoperative chest roentgenograms revealed that the distance between the epicardial surface and the posterior table of the sternum was larger in the Closure group compared to the Open group at 1 week and 3 months postoperatively (p < 0.001). Cardiac index and stroke work index in the early postoperative period was lower in the Closure group compared to the Open group (p < 0.001) despite similar filling pressures. CONCLUSIONS: Pericardial closure may reduce the risk of myocardial injury during sternotomy for repeat coronary artery bypass grafting by preventing right ventricular adhesions. However, adverse hemodynamic effects in the early postoperative period may preclude pericardial closure in patients with impaired ventricular function.
Aged↗
Coronary bypass and carotid endarterectomy: does a combined approach increase risk? A metaanalysis.
BACKGROUND: Patients with concomitant carotid and coronary artery disease present a surgical dilemma. We compared the stroke and mortality rates for combined coronary artery bypass grafting and carotid endarterectomy in which both procedures were performed under a single anesthetic, versus a staged approach, in which coronary artery bypass grafting and carotid endarterectomy were performed separately. METHODS: A computerized MEDLINE search supplemented with a manual bibliographic review was performed for all peer-reviewed English language publications that contained both combined and staged coronary artery bypass grafting/carotid endarterectomy patient cohorts. Outcomes of interest were stroke, death, and stroke or death; aggregation of outcome rates was performed with the Mantel-Haenszel method. RESULTS: Sixteen studies were identified with a total of 844 combined patients and 920 staged patients. None of the studies was completely randomized. The combined surgical group had a higher prevalence of unstable angina; the two groups had a similar prevalence of symptomatic carotid disease and severe carotid stenosis. Meta-analysis revealed a significantly increased risk of the composite end point, stroke or death, for patients undergoing combined procedures (relative risk 1.49; 95% confidence interval 1.03-2.15; p = 0.034). There was also a trend toward increased risk during combined procedures for the end points of stroke (relative risk 1.50; 95% confidence interval 0.97-2.32; p = 0.068) and death (relative risk 1.55; 95% confidence interval 0.94-2.53; p = 0.084) considered separately. The crude event rates for stroke were 6.0% versus 3.2% for combined versus staged procedure, 4.7% versus 2.9% for death, and 9.5% versus 5.7% for stroke or death. Two of the 16 individual studies showed a statistically significant increase in the risk of stroke or death for combined procedure (p < 0.05). CONCLUSIONS: Combined coronary artery bypass grafting and carotid endarterectomy may be associated with a higher risk of stroke or death than staged procedures. A randomized trial needs to be performed to determine the optimal management of patients with concomitant carotid and coronary artery disease.
Cerebrovascular Disorders↗
Myocardial perfusion during warm antegrade and retrograde cardioplegia: a contrast echo study.
BACKGROUND: We evaluated distribution of warm antegrade and retrograde cardioplegia in patients undergoing coronary artery bypass grafting (CABG). METHODS: Myocardial perfusion was evaluated pre- and post-CABG using transesophageal echocardiography with injection of sonicated albumin microbubbles (Albunex) during warm antegrade and retrograde cardioplegia. The left ventricle (LV) was evaluated in five segments and the right ventricle (RV) was evaluated in two segments. Segmental contrast enhancement was graded as absent (score = 0), suboptimal or weak (score = 1), optimal or excellent (score = 2), or excessive (score = 3). RESULTS: Pre-CABG cardioplegic perfusion correlated weakly with severity of coronary artery stenoses (r = -0.331 and 0.276 for antegrade and retrograde cardioplegia, respectively). Antegrade cardioplegia administration resulted in 98% and 96% perfusion to the left ventricle pre- and post-CABG, respectively. Retrograde cardioplegic administration resulted in reduced LV perfusion, with 86% (p = 0.032 from antegrade) and 59% (p<0.001 from antegrade) pre- and post-CABG, respectively. The average LV perfusion score (mean +/- SEM) was greater with antegrade than retrograde cardioplegia both pre-CABG (1.93+/-0.04 vs. 1.53+/-0.11, p<0.001) and post-CABG (1.63+/-0.07 vs. 1.19+/-0.13, p = 0.004). RV perfusion was poor with both techniques pre-CABG, but improved significantly with antegrade cardioplegia post-CABG. CONCLUSIONS: We conclude that warm antegrade cardioplegia results in better left ventricular perfusion than warm retrograde cardioplegia. Right ventricular cardioplegic perfusion was suboptimal, but the best delivery was achieved with antegrade cardioplegia after coronary bypass. We therefore recommend construction of the saphenous vein graft to the right coronary artery early in the operative procedure.
Aged↗
Intraoperative myocardial protection: current trends and future perspectives.
BACKGROUND: The results of contemporary coronary artery bypass graft surgery (CABG) are excellent. However, recently changing trends in the population at risk have necessitated new measures to minimize perioperative morbidity and mortality. METHODS: We reviewed cardioplegic innovations developed, evaluated, and currently employed at the Toronto Hospital. In addition, we conducted an evaluation of novel cardioplegic formulations, with an eye towards future clinical applications. RESULTS: At the Toronto Hospital, we demonstrated that blood provided better protection than crystalloid cardioplegia. Subsequently, we found that a terminal infusion of warm blood cardioplegia repleted myocardial adenosine triphosphate (ATP) levels and improved postoperative ventricular function. Recently, we reported that tepid (29 degrees C) cardioplegia reduced lactate and acid production during cardioplegic arrest, and improved postoperative ventricular function. Combining antegrade and retrograde cardioplegic delivery reduced lactate production, preserved ATP stores, and improved metabolic recovery after cross-clamp release. Cardioplegic flows of at least 200 mL/min were required to washout detrimental metabolic end-products and improve ventricular function. To further optimize myocardial protection, attempts have been made to harness the beneficial effects of ischemic preconditioning using adenosine. Similarly, insulin cardioplegia has been employed in order to enhance ventricular performance by stimulating early postoperative aerobic metabolism. Finally L-arginine, a nitric oxide donor has been demonstrated to be beneficial in experimental studies and may represent a further option for the enhancement of intraoperative myocardial protection. CONCLUSIONS: Despite continued improvements in cardioplegic techniques, low output syndrome following high-risk CABG remains an ongoing concern. The development of novel additives with various protective properties may provide added protection, allowing for a reduction morbidity and mortality following CABG.
Acid-Base Equilibrium↗
Decreased cerebral emboli during distal aortic arch cannulation: a randomized clinical trial.
BACKGROUND: Cerebral emboli occur during cardiopulmonary bypass and are a principal cause of postoperative neurologic dysfunction. We hypothesized that arterial cannulation of the distal aortic arch, with placement of the cannula tip beyond the left subclavian artery, will result in fewer cerebral microemboli than conventional cannulation of the ascending aorta. METHODS: Patients undergoing coronary bypass surgery with a single crossclamp technique were randomized to receive cannulation of the distal aortic arch (n = 17) or standard cannulation of the ascending aorta (control group, n = 17). Trendelenburg positioning was used whenever possible. Cerebral emboli were quantified by continuous transcranial Doppler monitoring of the middle cerebral artery. RESULTS: Baseline demographics were similar for the 2 groups of patients, including cardiopulmonary bypass and crossclamp times. Cerebral microemboli were detected during cardiopulmonary bypass in all patients, with a range of 17 to 627 emboli. The total number of detected emboli was lower in the arch cannulation group (152 +/- 33, mean +/- standard error of the mean) than in the conventional cannulation group (249 +/- 35, P =.04). Embolization rates were lower in distal arch patients than in control patients during cardiopulmonary bypass (2.0 +/- 0.3 vs 4.2 +/- 0.9 per minute, respectively, P =.03). Reduction in cerebral emboli by distal arch cannulation was most pronounced during perfusionist interventions. CONCLUSIONS: Cannulation of the distal aortic arch results in less cerebral microembolism than conventional cannulation of the ascending aorta. Provided it is performed safely, distal arch cannulation may be an important surgical option for patients with severe atherosclerosis of the ascending aorta.
Analysis of Variance↗
A novel comparison of stentless versus stented valves in the small aortic root.
BACKGROUND: Previous studies have compared prosthetic valves on the basis of industry-labeled valve sizes. Unfortunately, the relationship between the labeled size and the true measured external or internal diameter differs between valve manufacturers. Therefore hemodynamic comparisons between prosthetic valves are inaccurate if based solely on industry-labeled valve sizes. METHODS: We have previously demonstrated that the internal diameter of a 21-mm Carpentier-Edwards pericardial stented valve is similar to that of a 25-mm Toronto stentless porcine valve. Therefore we chose to compare postoperative hemodynamics in patients who received 19-, 21-, or 23-mm Carpentier-Edwards pericardial stented valves (inner diameter 18-22 mm, n = 69) with those in patients who received 23- or 25-mm stentless porcine valves (internal diameter 19-21 mm, n = 41). RESULTS: Patients in the Carpentier-Edwards group were more likely to be elderly and more likely to require concomitant revascularization. Operative mortality was lower in the stentless porcine valve group (0% vs 9%, P =.06). Hospital stay and ventilation requirements were shorter in the stentless porcine valve group. Postoperative hemodynamics were similar in the two groups. CONCLUSIONS: These data provide evidence that stentless and stented valves have similar hemodynamic profiles in the small aortic root when matched on true measured internal diameters. The clinical benefit of the stentless porcine valve may be due to patient selection or the lack of a rigid stent in the small aortic root, but it is not due to hemodynamic superiority over stented aortic valves of similar sizes.
Aged↗
The impact of age, coronary artery disease, and cardiac comorbidity on late survival after bioprosthetic aortic valve replacement.
OBJECTIVES: This study was designed to determine the effects of age, coronary artery disease and other cardiac comorbidities on late outcome following bioprosthetic aortic valve replacement. METHODS: Data were prospectively collected on 670 patients undergoing aortic valve replacement with the Hancock II bioprosthesis (Medtronic, Inc, Minneapolis, Minn) between 1982 and 1994. Mean patient age was 65 +/- 12 years (median, 68 years; range, 18-86 years). Follow-up was 99.7% complete at 69 +/- 40 months (median, 66 months; range, 0. 1-168 months). Survival and freedom from reoperation were evaluated univariately by Kaplan-Meier analysis and multivariably by Cox regression. RESULTS: After adjustment for gender, Cox regression analysis revealed that age of 65 years or older, left ventricular dysfunction, the presence of coronary artery disease, and advanced New York Heart Association functional classification were associated with a higher risk of late death. At 12 years, survival was significantly different by Kaplan-Meier analysis for both age younger than 65 years (71% +/- 4%) versus age 65 years or older (36% +/- 7%; P <.0001), left ventricular function grades 3 and 4 (26% +/- 13%) versus grades 1 and 2 (59% +/- 4%; P <.0001), no coronary artery disease (65% +/- 4%) versus coronary artery disease (35% +/- 8%; P <.0001), and functional class IV (33% +/- 9%) versus classes I to III (62% +/- 4%; P <.0001). Only 9 patients experienced primary tissue failure, all of whom were younger than 65 years of age. At 12 years, the freedom from primary tissue failure was 84% +/- 4% for those patients younger than 65 years of age, and 100% for those 65 years of age or older (P =.006). CONCLUSIONS: Long-term survival after aortic valve replacement is highly dependent on age, coronary artery disease, functional class, and left ventricular function, although bioprosthetic durability is dependent almost solely on age. Due to increased valve durability in patients who are 65 years of age or older, the Hancock II bioprosthesis may be an ideal aortic valve substitute in this age group. In patients who are younger than 65 years of age with advanced functional class, impaired left ventricular function, and coronary artery disease, this valve may also be used with a low probability of primary tissue failure. Patients without additional cardiac comorbidity may outlive their bioprosthetic valve, leading to reoperation.
Adult↗
The merits of percutaneous transluminal angioplasty of a superficial femoral artery stenosis via a retrograde popliteal artery approach.
Explore the source record for details and available documents.
Adult↗
The ubiquitin/proteasome pathway: friend or foe in zinc-, cadmium-, and H2O2-induced neuronal oxidative stress.
One of the hallmarks of neurodegeneration is the accumulation of ubiquitinated proteins in intraneuronal inclusions in the cytosol, endosomes/lysosomes and nuclei of affected cells. The relationship between inclusion production and cell viability is not well understood. On the one hand inclusions may be beneficial and result from an attempt of the cell to isolate a subclass of ubiquitinated proteins that are not effectively degraded. On the other hand, the inclusions may impede normal cell function contributing to cell death. To address this issue we treated mouse neuronal HT4 cells with three toxic agents cadmium, zinc and H2O2, and investigated their effects on glutathione homeostasis, on accumulation of ubiquitinated proteins and on cell viability. The three treatments induce oxidative stress manifested by decreases in glutathione (GSH) and/or increases in protein mixed disulfides (PrSSG). After an overnight recovery period in the absence of treatment, GSH and PrSSG were restored to almost normal levels. However, the levels of ubiquitinated proteins were significantly increased, and cell viability was sharply reduced. These results suggest that the ubiquitin-proteasome pathway is recruited for removal of proteins that are oxidatively modified. However, if the ubiquitinated proteins are not efficiently degraded, they accumulate in the cell and contribute to a decrease in cell viability.
Animals↗