Search PubMed⌕ Search

Biomedical subjects

J E Jordan

Publications and source records attributed to J E Jordan.

At least 19 recordsLinked to original sources
PubMed2026

Surgical Management of Young Women with High-Risk Breast Cancer Receiving Neoadjuvant Systemic Therapy on the I-SPY2 Trial.

BACKGROUND: Mastectomy rates in women with breast cancer are higher in younger women than in older women. The impact of this more extensive surgery on overall survival (OS) and locoregional recurrence in younger women is unknown, especially after neoadjuvant systemic therapy (NST). This study evaluated surgical management and outcomes of patients aged &#x2264; 45 versus > 45 years enrolled in multicenter NST clinical trial, I-SPY2.0 (NCT01042379, PMID 37325931). METHODS: We conducted a secondary data analysis comparing locoregional treatment in patients aged &#x2264; 45 versus > 45 years with clinical or molecular high-risk clinical stage II-III breast cancer treated from April 2010 to June 2022. Multivariate Cox proportional hazards models were used to evaluate associations between type of breast surgery with OS and locoregional recurrence-free interval by age group and tumor receptor subtype. RESULTS: Of 1737 patients, 698 (40.2%) were aged &#x2264; 45 years. There were no significant differences in patient or tumor characteristics or residual cancer burden distribution between age groups. Although breast-conserving surgery was significantly less common in younger women (36.8% vs 48.5%, p < 0.001), surgery type was not associated with OS or locoregional recurrence-free interval for patients aged &#x2264; 45 years. CONCLUSIONS: Greater extent of breast surgery was not associated with improved outcomes in women aged &#x2264; 45 years. Choice of surgical procedure in the management of breast cancer is multifactorial, but young age alone&#xa0;does not warrant mastectomy following NST.

Breast cancer↗
PubMed2001

Inhibition of mannose-binding lectin reduces postischemic myocardial reperfusion injury.

BACKGROUND: Complement consists of a complex cascade of proteins involved in innate and adaptive immunity. The cascade can be activated through 3 distinct mechanisms, designated the classical, alternative, and lectin pathways. Although complement is widely accepted as participating in the pathophysiology of ischemia-reperfusion injury, the specific role of the lectin pathway has not been addressed. METHODS AND RESULTS: Monoclonal antibodies (mAbs; P7E4 and 14C3.74, IgG1kappa isotypes) were raised against rat mannose-binding lectin (rMBL). Both mAbs recognized rMBL-A by Western analysis or surface plasmon resonance. P7E4, but not 14C3.74, exhibited a concentration-dependent inhibition of the lectin pathway, with maximal effect at 10 microg/mL. In vivo, rats were subjected to 30 minutes of left coronary artery occlusion and 4 hours of reperfusion. Complement C3 deposition was greatly attenuated in hearts pretreated with P7E4 compared with 14C3.74-treated hearts. Pretreatment with P7E4 (1 mg/kg) significantly reduced myocardial creatine kinase loss (48%), infarct size (39%), and neutrophil infiltration (47%) compared with 14C3.74-treated animals. In addition, P7E4 pretreatment significantly attenuated the expression of proinflammatory genes (intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and interleukin-6) after ischemia-reperfusion. CONCLUSIONS: The lectin complement pathway is activated after myocardial ischemia-reperfusion and leads to tissue injury. Blockade of the lectin pathway with inhibitory mAbs protects the heart from ischemia-reperfusion by reducing neutrophil infiltration and attenuating proinflammatory gene expression.

Animals↗
PubMed2000

Recombinant human complement C5a receptor antagonist reduces infarct size after surgical revascularization.

OBJECTIVES: This study tested the hypothesis that a recombinant human C5a antagonist, CGS 32359, attenuates neutrophil activation and reduces infarct size in a porcine model of surgical revascularization. METHODS: CGS 32359 (0.16-16 micromol/L) dose-dependently inhibited superoxide production by human C5a-activated porcine neutrophils (18 +/- 3.7 vs 1.6 +/- 0.5 nmol/5 min/5 x 10(6) neutrophils; P <.05) and reduced neutrophil adherence to coronary endothelium from 194 +/- 9 to 43 +/- 6 neutrophils/mm(2) (P <.05). The left anterior descending coronary artery was occluded for 50 minutes, after which saline solution (n = 8), mannitol-buffer vehicle (n = 9, 102 mg/kg bolus, 102 mg. kg(-1). h(-1)), or CGS 32359 (CGS, n = 7, 60 mg/kg bolus, 60 mg. kg(-1). h(-1)) was infused. After ischemia, 1-hour arrest was achieved by means of multidose hypothermic (4 degrees C) blood cardioplegia, followed by 2.5 hours of off-bypass reperfusion. The ligature on the left anterior descending artery was released before the second infusion of cardioplegic solution. RESULTS: Area at risk was similar in all groups (saline solution, 27% +/- 2%; mannitol-buffer vehicle, 26% +/- 2%; CGS, 26% +/- 2% left ventricular mass). Infarct size (area necrosis/area at risk) was significantly reduced by CGS (18% +/- 6%, P <.05) versus saline solution (52% +/- 3%) and mannitol-buffer vehicle (60% +/- 4%). Postischemic systolic shortening (sonomicrometry) in the area at risk was significantly improved with CGS (0.8% +/- 0.9%) compared with saline solution (-3.7% +/- 1.1%) and mannitol-buffer vehicle (-6.4% +/- 1.0%). Myeloperoxidase activity from accumulated neutrophils was less in the ischemic zone of CGS (0.014 +/- 0.002 U/100 mg tissue; P <.05) than mannitol-buffer vehicle (0.133 +/- 0.012 U/100 mg tissue). CONCLUSIONS: We conclude that the recombinant human C5a receptor antagonist CGS 32359 inhibits surgical ischemia-reperfusion injury after coronary occlusion.

Analysis of Variance↗
PubMed2000

Genetic technology and testing: perceptions of allied health professional education departmental chairs.

This study elicited a preliminary report that reflected the perspectives and interest of health professional academicians in regard to the need for and appropriateness of genetic technology and testing information in their curricula. Of the original attainable sample of 135 departmental chairs of allied health professional education programs nationwide, 88 responded to a mailed questionnaire, for a response rate of 65%. Of the 88, 11 (13%) saw no need for such information to be provided for allied health students at the undergraduate or graduate level or for currently practicing allied health professionals (AHPs). Consequently, the elicited results were based on the responses of the other respondents who perceived a need for genetic technology and testing information to be made available to both AHP students (86% undergraduate and 92% graduate) and currently practicing AHPs (91%). In regard to preferences for required and/or recommended student exposures to and participation in genetic technology information and coursework, their responses varied.

Allied Health Personnel↗
PubMed2000

Economic and outcomes assessment of magnetic resonance imaging in the evaluation of headache.

We sought to evaluate the economic impact and diagnostic utility of magnetic resonance imaging (MRI) in the management of patients with headache and nonfocal physical examinations. Computerized medical records were retrospectively reviewed of 1,233 patients presenting for MRI of headache at our institution over a 3-year period (1992-1995). Patients with focal findings at physical examination, prior brain surgery, head trauma, or immunocompromise were excluded. A model was developed to assess the cost associated with the MR test results, and actual average institutional costs of performing an examination applied. Correlative statistical analysis of referring specialties and positive tests was also performed. Three hundred twenty-eight patients who met the above criteria were retained in the sample. One hundred sixty-three patients (50%) had negative MR test results. Of the 50% of patients with positive studies, only 5 (1.5%) had clinically significant MR results. The average cost of an MR examination was 517 dollars (1998 dollars). The cost per clinically significant managed case detected was 34,535 dollars. No statistically significant difference was found among referring specialties and clinically significant MR results. Our results indicate that MRI of nonfocal headache yields a low percentage of positive clinically significant results and has limited cost-effectiveness. Referring specialty had no significant bearing on these outcomes, regardless of specialist experience.

Adolescent↗
PubMed1999

Nitric oxide and the vascular endothelium in myocardial ischemia-reperfusion injury.

The normal coronary vascular endothelium (VE) tonically releases nitric oxide (NO) by converting L-arginine to citrulline by a constitutive NO synthase. Reperfusion after myocardial ischemia reduces basal and stimulated release of NO. This "vascular reperfusion injury" is mediated largely by neutrophils (PMN) through specific interactions between adhesion molecules on the endothelium and the PMN, an interaction that precedes myocyte injury. NO inhibits the PMN-mediated reperfusion injury by direct effects on both the PMN and the vascular endothelium. Cardioprotective strategies include augmentation of endogenous NO by the precursor L-arginine and the administration of exogenous NO donors at the time of perfusion, which (1) attenuates PMN adherence to the coronary artery and venous endothelium, (2) reduces PMN-mediated endothelial dysfunction, (3) reduces PMN accumulation in the area at risk, and (4) reduces infarct size. Hence, NO represents a powerful therapeutic tool with which to attenuate the consequences of ischemia-reperfusion injury on vascular injury and infarction.

Animals↗
PubMed1999

Adenosine A3 pretreatment before cardioplegic arrest attenuates postischemic cardiac dysfunction.

BACKGROUND: The cardioprotective effects of the adenosine A3 receptor in a cardioplegia model have not been described. We tested the hypothesis that infusion of the A3 receptor agonist, Cl-IB-MECA (100 nM), as a pretreatment (PTx) and/or as a cardioplegic (CP) additive reduces postischemic myocardial injury. METHODS: Isolated perfused rat hearts underwent 30 minutes of normothermic ischemia, 60 minutes of intermittent hypothermic cardioplegia (10 degrees C), followed by 2 hours of reperfusion. Hearts were divided into four groups: (1) no pretreatment (PTx) and unsupplemented cardioplegia (CP) (control), (2) Cl-IB-MECA PTx and unsupplemented CP (A3-PTx), (3) no PTx and Cl-IB-MECA CP (A3-CP), or (4) Cl-IB-MECA PTx and Cl-IB-MECA CP (A3-[PTx+CP]). RESULTS: Coronary flow was not increased after A3 pretreatment when compared to baseline values. After 2 hours of reperfusion, left ventricular developed pressure in control and A3-CP groups was depressed to 43% +/- 3% and 47% +/- 2% of baseline; while A3-PTx and A3-[PTx+CP] significantly increased left ventricular developed pressure (65% +/- 3% and 61% +/- 5%) from baseline relative to control and A3-CP. Effluent creatine kinase activity was significantly decreased by A3-PTx (1520 +/- 32 IU/L), A3-[PTx+CP] (1481 +/- 41 IU/L) from control (1734 +/- 54 IU/L) and A3-CP (1750 +/- 43 IU/L). Myocardial edema (% tissue water) was significantly less in A3-PTx (78 +/- 0.6%) and A3-[PTx+CP] (76% +/- 2%) compared with control (85% +/- 0.4%) and A3-CP (83% +/- 2%). CONCLUSIONS: Adenosine A3 receptor stimulation as a pretreatment attenuates postischemic cardiodynamic dysfunction and creatine kinase release but has no cardioprotection as an adjunct to cold cardioplegia.

Adenosine↗
PubMed1999

Broad-spectrum cardioprotection with adenosine.

Ischemia-reperfusion results in contractile dysfunction, necrosis, and vascular injury. This postischemic injury is mediated in part by superoxide radical production, neutrophils, dysfunction to ionic pumps, and edema formation. Adenosine is an autacoid released tonically by myocytes, endothelium, and neutrophils; the release of adenosine from the myocyte compartment into the interstitium is increased during ischemia. The major effects of adenosine are mediated by specific receptors identified as A1, A2a, A2b, and A3. Each receptor subtype contributes to physiological responses that influence ischemia-reperfusion injury. Adenosine has potent cardioprotective properties exerted during three major windows of opportunity: pretreatment, ischemia, and reperfusion. The cardioprotective effects exerted during pretreatment and ischemia may involve metabolic changes and hyperpolarization via K(ATP)-channel activation, mediated through A1 receptor mechanisms. The cardioprotective mechanisms exerted during reperfusion involve inhibition of neutrophils directly (superoxide anion generation, expression of adhesion molecules), and by inhibiting activation of the endothelium through A2 receptor-mediated mechanisms, thereby preventing neutrophil-endothelial cell interactions, which initiate the inflammatory-like component of reperfusion injury. Activation of the newly identified A3 receptor has been shown to be cardioprotective partially by inhibition of neutrophil adherence to endothelium and by neutrophil-independent mechanisms. These mechanisms of cardioprotection have been suggested to play major roles in the reduction of infarction and apoptosis after myocardial ischemia, cardioplegic arrest, and subsequent reperfusion. Adenosine has been used as an adjunct to both crystalloid and blood cardioplegia, but its potential as a cardioprotective agent has not been fully explored.

Adenosine↗
PubMed1999

The role of neutrophils in myocardial ischemia-reperfusion injury.

Reperfusion of ischemic myocardium is necessary to salvage tissue from eventual death. However, reperfusion after even brief periods of ischemia is associated with pathologic changes that represent either an acceleration of processes initiated during ischemia per se, or new pathophysiological changes that were initiated after reperfusion. This 'reperfusion injury' shares many characteristics with inflammatory responses in the myocardium. Neutrophils feature prominently in this inflammatory component of postischemic injury. Ischemia-reperfusion prompts a release of oxygen free radicals, cytokines and other proinflammatory mediators that activate both the neutrophils and the coronary vascular endothelium. Activation of these cell types promotes the expression of adhesion molecules on both the neutrophils and endothelium, which recruits neutrophils to the surface of the endothelium and initiate a specific cascade of cell-cell interactions, leading first to adherence of neutrophils to the vascular endothelium, followed later by transendothelial migration and direct interaction with myocytes. This specific series of events is a prerequisite to the phenotypic expression of reperfusion injury, including endothelial dysfunction, microvascular collapse and blood flow defects, myocardial infarction and apoptosis. Pharmacologic therapy can target the various components in this critical series of events. Effective targets for these pharmacologic agents include: (a) inhibiting the release or accumulation of proinflammatory mediators, (b) altering neutrophil or endothelial cell activation and (c) attenuating adhesion molecule expression on endothelium, neutrophils and myocytes. Monoclonal antibodies to adhesion molecules (P-selectin, L-selectin, CD11, CD18), complement fragments and receptors attenuate neutrophil-mediated injury (vascular injury, infarction), but clinical application may encounter limitations due to antigen-antibody reactions with the peptides. Humanized antibodies and non-peptide agents, such as oligosaccharide analogs to sialyl Lewis, may prove effective in this regard. Both nitric oxide and adenosine exhibit broad spectrum effects against neutrophil-mediated events and, therefore, can intervene at several critical points in the ischemic-reperfusion response, and may offer greater benefit than agents that interdict at a single point in the cascade. The understanding of the molecular processes regulating actions of neutrophils in ischemic-reperfusion injury may be applicable to other clinical situations, such as trauma, shock and organ or tissue (i.e. vascular conduits) transplantation.

Adenosine↗
PubMed1999

Ischemic preconditioning attenuates postischemic coronary artery endothelial dysfunction in a model of minimally invasive direct coronary artery bypass grafting.

OBJECTIVE: Unmodified reperfusion without cardioplegia in minimally invasive direct coronary artery bypass grafting procedures causes endothelial dysfunction that may predispose to polymorphonuclear neutrophil-mediated myocardial injury. This study tested the hypothesis that ischemic preconditioning in a minimally invasive direct coronary artery bypass grafting model attenuates postischemic endothelial dysfunction in coronary vessels. METHODS: In anesthetized dogs, the left anterior descending coronary artery was occluded for 30 minutes and reperfused for 3 hours without ischemic preconditioning (no-ischemic preconditioning; n = 7); in 7 dogs, the left anterior descending occlusion was preceded by 5 minutes occlusion followed by 5 minutes of reperfusion. Relaxation responses to stimulators of nitric oxide synthase were used to evaluate endothelial function in arteries from the ischemic-reperfused (left anterior descending) and nonischemic (left circumflex coronary artery) zones. RESULTS: Stimulated endothelial-dependent relaxation of epicardial left anterior descending artery to incremental concentrations of acetylcholine in the no-ischemic preconditioning animals was shifted to the right, and maximal relaxation was attenuated compared with the nonischemic left circumflex coronary artery (117% +/- 4% vs 138% +/- 5%). In contrast, acetylcholine-induced maximal relaxation was comparable in the left anterior descending artery versus left circumflex coronary artery in the ischemic preconditioning group (130% +/- 6% vs 135% +/- 5%). In 150- to 200- microm left anterior descending microvessels, 50% relaxation occurred with a lower concentration (log[M]) of acetylcholine in ischemic preconditioning versus no-ischemic preconditioning (-8.0 +/- 0.4 vs -7.0 +/- 0.1) with no group differences in smooth muscle relaxation to sodium nitroprusside, suggesting endothelial-specific damage. Adherence of fluorescent labeled polymorphonuclear neutrophils to epicardial coronary artery endothelium, used as an index of basal (unstimulated) anti-polymorphonuclear neutrophil function, was significantly attenuated by ischemic preconditioning versus no-ischemic preconditioning (293 +/- 25 polymorphonuclear neutrophils/mm2 vs 528 +/- 29 polymorphonuclear neutrophils/mm2). CONCLUSION: In this minimally invasive direct coronary artery bypass grafting model, both agonist-stimulated and basal postischemic endothelial dysfunction were attenuated by ischemic preconditioning.

Analysis of Variance↗
PubMed1999

Adenosine A(3)-receptor stimulation attenuates postischemic dysfunction through K(ATP) channels.

We tested the hypothesis that selective adenosine A(3)-receptor stimulation reduces postischemic contractile dysfunction through activation of ATP-sensitive potassium (K(ATP)) channels. Isolated, buffer-perfused rat hearts (n = 8/group) were not drug pretreated (control) or were pretreated with adenosine (20 microM), 2-chloro-N(6)-(3-iodobenzyl)-adenosine-5'-N-methyluronamide (Cl-IB-MECA; A(3) agonist, 100 nM), Cl-IB-MECA + 8-(3-noradamantyl)-1,3-dipropylxanthine (KW-3902; A(1) antagonist, 5 microM), Cl-IB-MECA + glibenclamide (Glib; K(ATP)-channel blocker, 0. 3 microM), or Glib alone for 12 min before 30 min of global normothermic ischemia followed by 2 h of reperfusion. After 2 h of reperfusion, left ventricular developed pressure (LVDP, %baseline) in control hearts was depressed to 34 +/- 2%. In hearts pretreated with Cl-IB-MECA, there was a statistically significant increase in LVDP (50 +/- 6%), which was reversed with coadministration of Glib (37 +/- 1%). Control hearts also showed similar decreases in left ventricular peak positive rate of change in pressure (dP/dt). Therefore, the A(3) agonist significantly attenuated postischemic cardiodynamic injury compared with the control, which was reversed by Glib. Cumulative creatine kinase (CK in U/min) activity was most pronounced in the control group (10.4 +/- 0.6) and was significantly decreased by Cl-IB-MECA (7.5 +/- 0.4), which was reversed by coadministration of Glib (9.4 +/- 0.2). Coronary flow was increased during adenosine infusion (160% of baseline) but not during Cl-IB-MECA infusion. Effects of Cl-IB-MECA were not reversed by the specific A(1) antagonist KW-3902. We conclude that cardioprotection afforded by A(3)-receptor stimulation may be mediated in part by K(ATP) channels. Cl-IB-MECA may be an effective pretreatment agent that attenuates postischemic cardiodynamic dysfunction and CK release without the vasodilator liability of other adenosine agonists.

Adenosine↗
PubMed1999

A(3) adenosine receptor activation attenuates neutrophil function and neutrophil-mediated reperfusion injury.

This study tested the hypothesis that A(3) adenosine receptors inhibit neutrophil (PMN) function and PMN-mediated reperfusion injury. 2-Chloro-N(6)-(3-iodobenzyl)adenosine-5'-N-methyluronamide (Cl-IB-MECA), an A(3) agonist, did not attenuate superoxide production or myeloperoxidase release from stimulated PMNs. However, Cl-IB-MECA reduced platelet-activating factor-stimulated PMN adherence to coronary endothelium at low concentrations: 52 +/- 27, 45 +/- 10, and 87 +/- 23 PMNs/mm(2) at 0.1, 1.0, and 10 nM vs. 422 +/- 64 PMNs/mm(2) with platelet-activating factor alone. This inhibition was not blocked by A(1) (5 microM KW-3902) or A(2a) (5 microM KF-21326) antagonists: 44 +/- 3 and 43 +/- 2 PMNs/mm(2), respectively. Endothelial pretreatment with 1 nM Cl-IB-MECA reduced PMN adherence, which was reversed by the A(3) antagonist MRS-1220 (100 nM). PMN-mediated reperfusion injury was initiated in isolated rabbit hearts by infusion of 28 x 10(6) PMNs/min for 10 min early in reperfusion. PMNs caused a significant decrease in recovery of left ventricular developed pressure and positive and negative time derivatives of pressure (23 +/- 3, 25 +/- 3, and 23 +/- 3% of baseline, respectively) vs. buffer-perfused hearts (43 +/- 7, 44 +/- 7, and 45 +/- 6%, respectively). Cl-IB-MECA (10 nM) given at reperfusion attenuated the PMN-mediated loss of contractile recovery (40 +/- 3, 46 +/- 5, and 42 +/- 4% of baseline). Cl-IB-MECA reduced myeloperoxidase release activity (5.3 +/- 0.6 absorbance units/min) and CD18-positive cells (54 +/- 9 cells/slide) compared with the untreated PMN group (17.9 +/- 1.7 absorbance units/min and 183 +/- 68 cells/slide). We conclude that Cl-IB-MECA attenuates reperfusion injury by decreasing PMN-endothelial cell interactions. These results suggest that the A(3) adenosine receptor may be a novel therapeutic target for treatment of myocardial ischemia and reperfusion.

Animals↗
PubMed1997

Gradual reperfusion reduces infarct size and endothelial injury but augments neutrophil accumulation.

BACKGROUND: Reperfusion causes injury to the coronary artery endothelium primarily by neutrophil-mediated mechanisms. However, factors other than neutrophils may govern the extent of myocardial necrosis. This study tests the hypothesis that gradual initiation of reflow will reduce reperfusion injury and preserve postischemic endothelial function. METHODS: In 16 anesthetized dogs, the left anterior descending artery was ligated for 60 minutes. In one group, reperfusion was initiated abruptly (abrupt, n = 8), whereas in the gradual reperfusion group (ramp, n = 8), flow was slowly initiated during the first 30 minutes of reperfusion. After reperfusion, coronary artery segments were isolated to assess postischemic endothelial function. RESULTS: Infarct size (area of necrosis/area at risk) was significantly reduced in the ramp group (28.2% +/- 2.0%) compared with abrupt (41.6% +/- 1.4%). Neutrophil accumulation (myeloperoxidase) in the area at risk was significantly greater in the ramp group compared with abrupt (8.0 +/- 1.3 versus 3.5 +/- 0.8 U/g tissue). In isolated postischemic left anterior descending arterial rings, the concentration of acetylcholine that elicited a response 50% of the maximum possible response was significantly greater in abrupt (-6.88 +/- 0.04 log [mol/L]) than ramp (-7.62 +/- 0.04 log [mol/L]) and control (-7.68 +/- 0.003 log [mol/L]), suggesting endothelial dysfunction. The concentration of A23187 that elicited a response 50% of the maximum possible response was similarly greater in abrupt (-7.24 +/- 0.03 log [mol/L]) versus ramp (-7.62 +/- 0.03 log [mol/L]) and control (-7.8 +/- 0.04 log [mol/L]). Smooth muscle dysfunction (response to sodium nitrite) also occurred in the abrupt rings. CONCLUSIONS: Gradual reperfusion of an ischemic area reduces infarct size and preserves endothelial function but paradoxically increases neutrophil accumulation within the area at risk.

Animals↗
PubMed1997

Basal nitric oxide expresses endogenous cardioprotection during reperfusion by inhibition of neutrophil-mediated damage after surgical revascularization.

Ischemia-reperfusion damages endothelium and impairs basal production of nitric oxide. Basally released nitric oxide is cardioprotective by its inhibition of neutrophil activities. Loss of endogenous nitric oxide with endothelial injury may occur during two phases: cardioplegic ischemia and reperfusion (aortic declamping). This study tested the hypothesis that inhibition of endogenously released nitric oxide in hearts subjected to regional ischemia, cardioplegic arrest, and reperfusion (1) restricts endogenous cardioprotection and permits neutrophil-mediated damage and (2) expresses damage during the reperfusion phase. L-Nitro-arginine was used to block basal nitric oxide production. In 22 anesthetized dogs, the left anterior descending artery was ligated for 90 minutes followed by 1 hour of arrest with cold multidose (every 20 minutes) blood cardioplegia. Dogs were divided into three groups: the first group received standard unsupplemented blood cardioplegia (group 1, n = 8), in the second group L-nitro-arginine was administered as an additive to blood cardioplegic solution (1 mmol) and as an infusion during reperfusion (34 mg/kg) (group 2, n = 7), and in the third group L-nitro-arginine was administered only at reperfusion (group 3, n = 7). The ligature was released during the second infusion of cardioplegic solution. Infarct size (triphenyltetrazolium chloride) was increased in group 3 (L-nitro-arginine only at reperfusion) compared with that in group 1 (standard blood cardioplegia) (49% +/- 6% vs 34% +/- 2%, respectively), but was not further extended in group 2 (L-nitro-arginine as an additive to blood cardioplegic solution and at reperfusion) (56% +/- 3%, p > 0.05 vs group 3), which suggests primarily a reperfusion process. Polymorphonuclear neutrophil-specific myeloperoxidase activity in the area at risk was elevated comparably in groups 2 and 3 (group 2: 2.9 +/- 0.5 units/gm tissue, p = 0.06 vs group 1; group 3: 3.9 +/- 1.0 units/gm tissue, p < 0.05 vs group 1) compared with that in the standard blood cardioplegia group (1.7 +/- 0.3 units/gm tissue), suggesting polymorphonuclear neutrophil accumulation occurs primarily during reperfusion. Polymorphonuclear neutrophil adherence in ischemic-reperfused left anterior descending artery segments was comparably greater in group 2 (L-nitro-arginine as an additive to blood cardioplegic solution and at reperfusion: 195 +/- 21 polymorphonuclear neutrophils/mm2 of artery, p < 0.05 vs group 1) and group 3 (L-nitro-arginine only at reperfusion: 224 +/- 20 polymorphonuclear neutrophils/mm2 of artery, p < 0.05 vs group 1) relative to that in group 1 (108 +/- 19 polymorphonuclear neutrophils/mm2 of artery). There was no significant adherence to nonischemic circumflex arteries. We conclude that blockade of endogenous nitric oxide augments postischemic injury mediated by polymorphonuclear neutrophils, and this damage is expressed primarily during the reperfusion phase.

Animals↗
PubMed1997

Resource utilization and work or school loss reported by patients with diabetes: experience in diabetes training programs.

Diabetes exerts a major economic impact on healthcare in the United States both in terms of direct and indirect costs. Diabetes management and education programs designed to assist patients in achieving more optimal glycemic control represent a potential mechanism for reducing the morbidity and costs associated with diabetes. The relationship between HbA1c and patient hospitalizations and between HbA1c and days lost from work or school related to diabetes within the past year were evaluated. A cohort of 2359 patients with diabetes (188 type I, 2171 type II) referred to a comprehensive diabetes self-management training program was included in the analyses. Overall, 350 (14.8%) patients reported hospitalization, and 212 (9.0%) reported days lost from work or school. Patients with type I diabetes reported more hospitalizations (26.1% vs 13.9% and days lost (19.2% vs 8.1%) than type II patients. For the hospitalization outcome, the multivariate analyses indicated that younger age, the number of co-morbidities, and the duration of diabetes exerted a greater influence on the reported numbers of hospitalization than glycemic control. For the days lost outcome, the multivariate analyses indicated that there was a marginally significant association between patients with poor glycemic control and reported work or school loss related to diabetes (odds ratio = 1.5; 95% confidence interval, 1.0-2.2). These data suggest that interventions that improve glycemic control may decrease indirect costs related to diabetes.

Absenteeism↗
PubMed1997

Adenosine A2 receptor activation attenuates reperfusion injury by inhibiting neutrophil accumulation, superoxide generation and coronary endothelial adherence.

This study tests the hypothesis that adenosine A2 receptor activation reduces reperfusion injury by inhibiting neutrophils in a canine model of ischemia and reperfusion. In 16 anesthetized, open-chest dogs, the left anterior descending coronary artery was ligated for 60 min and reperfused for 3 hr. An intracoronary infusion of either the selective adenosine A2 agonist CGS-21680 at 0.2 microgram/kg/min (n = 8) or vehicle (n = 8) was started 5 min before reperfusion and discontinued after 60 min. The area at risk was comparable between vehicle-treated and CGS-21680-treated groups (39.6 +/- 4.1 vs. 37.1 +/- 2.5% of left ventricle). Infarction size, determined with triphenyltetrazolium chloride, was smaller in the CGS-21680-treated group than in the vehicle-treated group (15.4 +/- 2.9 vs. 29.8 +/- 2.3% of area at risk, P < .05 vs. vehicle-treated group). CGS-21680 significantly reduced neutrophil accumulation (myeloperoxidase activity) in the nonnecrotic area at risk tissue, compared with the vehicle-treated group (2.12 +/- 0.5 vs. 6.47 +/- 0.6 U/g of tissue, P < .05 vs. vehicle-treated group). In in vitro studies, CGS-21680 reduced platelet-activating factor (PAF)-activated canine neutrophil adherence to the endothelial surface of normal homologous coronary artery segments. Compared with PAF-stimulated neutrophils (188.4 +/- 9.4 adhered neutrophils/mm2), CGS-21680 reduced adherence close to base-line levels (46.6 +/- 5.8 adhered neutrophils/mm2) at concentrations of 10 microM (65.6 +/- 8.2 adhered neutrophils/mm2, P < .05 vs. PAF-stimulated group) and 50 microM (56.6 +/- 4.6 adhered neutrophils/mm2, P < .05 vs. PAF-stimulated group). Superoxide anion production (cytochrome c reduction) by activated neutrophils was reduced by CGS-21680 from 33.8 +/- 5.0 to 8.9 +/- 3.6 nmol/5 min/5 x 10(5) cells (P < .05 vs. PAF-stimulated group). We conclude that specific A2 receptor stimulation with CGS-21680 at reflow reduces reperfusion injury by inhibiting neutrophil-related processes.

Adenosine↗
PubMed1996

Patterns of contrast enhancement in the pediatric spine at MR imaging with single- and triple-dose gadolinium.

PURPOSE: To assess patterns of nerve root and spinal cord contrast enhancement in the pediatric spine at magnetic resonance (MR) imaging with single- and triple-dose gadolinium. MATERIALS AND METHODS: In three control patients with no suspected pathologic spinal condition and 19 patients with a suspected condition, spinal cords were evaluated prospectively for potential spread of tumor to cerebrospinal fluid ("drop metastases") (n = 18) or Guillain-Barré syndrome (n = 1). After enhancement with 0.1 mmol/kg gadolinium, patients without definite drop metastases (n = 8) received a booster of 0.2 mmol/kg gadolinium 30-40 minutes later; clinical follow-up was obtained 12 1/2 to 19 months later. RESULTS: Drop metastases appeared as nodular areas of enhancement in 11 patients. Vascular enhancement related to the spinal cord surface and emerging nerve roots was observed in images obtained in all control patients, as well as in patients with negative findings at lumbar puncture and at clinical or MR imaging follow-up examination (n = 6). Vascular and nerve root enhancement increased with triple-dose gadolinium and was greater in patients after radiation therapy (n = 17) than in control patients (n = 3). CONCLUSION: Use of triple-dose gadolinium did not result in detection of additional cases of drop metastases.

Adolescent↗