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Biomedical subjects

J J Lopez

Publications and source records attributed to J J Lopez.

At least 19 recordsLinked to original sources

Mechanisms of reactions of flavin mononucleotide triplet with aromatic amino acids.

Chemical reactions between the photoexcited triplet state of flavin mononucleotide and the aromatic amino acids, N-acetyl tryptophan (TrpH), N-acetyl tyrosine (TyrOH), and N-acetyl histidine (HisH) in aqueous solution have been studied in the pH range 2-12. Across the whole pH range, the principal mechanism of reaction of both TrpH and TyrOH is shown to be electron transfer. For HisH, the mechanism and rate of the reaction depend on the protonation state of the reactants. In acidic conditions (pH < 4), reaction does not occur. At 4 < pH < 11, the reaction proceeds via hydrogen atom abstraction with a rate constant varying from 3.0 x 10(6) to 2.5 x 10(8) M(-1) s(-1). In extremely basic solution (pH > 12) the mechanism switches to electron transfer.

Amino Acids, Aromatic↗

Effects of surfactants on the photosensitized production of tyrosine radicals studied by photo-CIDNP.

The influence of the surfactants sodium dodecyl sulphate, cetyltrimethyl-ammonium bromide and triton X-100 on the photochemically induced dynamic nuclear polarization (CIDNP) of N-acetyl tyrosine has been investigated. Three photosensitizers were used to generate polarization: thionin, eosin Y and flavin mononucleotide. 600 MHz 1H photo-CIDNP experiments, supported by laser flash photolysis transient absorption measurements, indicate that the neutral triton surfactant has no influence on the nuclear polarization, but that the other two, charged, amphiphiles affect the photochemistry in a variety of ways, depending on the surfactant concentration and the identity of the sensitizer.

Journal Article↗

Improved photo-CIDNP methods for studying protein structure and folding.

Two new techniques offering considerable improvements in the quality of 1H photo-CIDNP spectra of proteins are demonstrated. Both focus on the problem of progressive photo-degradation of the flavin dye used to generate polarization in exposed tryptophan, tyrosine and histidine side-chains. One approach uses rapid addition and removal of protein/flavin solution between light flashes to mix the NMR sample and introduce fresh dye into the laser-irradiated region. The other involves chemical oxidation of photo-reduced flavin by the addition of hydrogen peroxide. In both cases a larger number of scans can be accumulated before the flavin is exhausted than would otherwise be possible. The techniques are demonstrated by 600 MHz CIDNP-NOESY spectroscopy of bovine holo-alpha-lactalbumin, and by real-time CIDNP observation of the refolding of bovine apo-alpha-lactalbumin following rapid dilution from a high concentration of chemical denaturant.

Animals↗

Acute myocardial infarction: a rare presentation of pancreatic carcinoma.

Secondary neoplastic involvement of the heart is common but usually asymptomatic. Malignancy rarely presents as acute pericarditis, cardiac tamponade, and myocardial infarction in the same patient. We report a patient with unsuspected metastatic pancreatic adenocarcinoma who presented with acute pericarditis and cardiac tamponade and subsequently developed a myocardial infarction due to coronary artery occlusion secondary to a metastatic deposit around the left anterior descending artery.

Adenocarcinoma↗

VEGF administration in chronic myocardial ischemia in pigs.

OBJECTIVE: Previous investigations have shown the effectiveness of sustained intra- or extravascular administration of vascular endothelial growth factor (VEGF) in chronic myocardial ischemia in improvement of left ventricular function. The present investigations were undertaken in order to evaluate efficacy of a single bolus or local intracoronary delivery. METHODS: Yorkshire pigs underwent placement of a left circumflex artery ameroid occluder. Three weeks later the animals were randomized to treatment with VEGF (20 micrograms) accomplished by local intracoronary delivery system (InfusaSleeve, n = 10), intracoronary bolus infusion (n = 7) or by epicardial implantation of an osmotic delivery system (n = 7). An additional group of animals received intracoronary administration of saline and served as a control (n = 9). Three weeks after initiation of therapy, the animals were evaluated with regard to myocardial perfusion and global as well as regional ventricular function. RESULTS: All three VEGF treatment groups but not the control animals demonstrated a significant increase in the left-to-left (but not right-to-left) collateral index, myocardial blood flow (pre-therapy LCX vs. LAD (average of all groups): 0.76 +/- 0.35 vs. 0.96 +/- 0.38 ml*min-1*g-1, p = 0.03; post-therapy: LCX vs. LAD: 1.16 +/- 0.39 vs. 1.15 +/- 0.28 ml*min-1*g-1, p = NS) and coronary vasodilatory reserve 3 weeks after growth factor administration. The observed increase in VEGF-induced perfusion correlated with improvement in regional ventricular function in all VEGF-treated groups (pre-therapy vs. post-therapy: i.c. VEGF 20 +/- 5.1 vs. 33 +/- 4.8; local VEGF 16 +/- 2.8 vs. 33.6; pump VEGF 17 +/- 3.8 vs. 34 +/- 4.9 p < 0.05 for all) but not control animals (21 +/- 3.3 vs. 27 +/- 5.8, p = NS). CONCLUSION: Single intracoronary delivery (intravascular bolus or local delivery) of VEGF is effective in stimulating physiologically significant angiogenesis in porcine model of chronic myocardial ischemia.

Animals↗

Quality differences between rural and urban primary care: the case of a cervical cancer screening programme.

OBJECTIVE: To measure the difference between rural and urban primary care quality in terms of an early cervical cancer detection programme. LOCATIONS: Seven hundred and fifty smear reports from rural primary care units and 750 from urban primary care units were selected at random from three institutions: the Ministry of Health, the largest Mexican social security institution, and one University Hospital, during August 1995-March 1996. Excluded were reports from women who were pregnant, menopausal or those who had undergone hysterectomy, as well as those tested positive for dysplasia and cancer. ACTIVITIES: Quality was measured through indicators and standards set by consensus of recognized field experts, based mainly on recommended national and international parameters. RESULTS: There was no difference between the overall quality of the urban and rural units. Both registered fairly satisfactory levels (achievement: 76.2%; 95% CI: 72.7-77.0%, versus 75.2; 95% CI: 69.8-78.9%, respectively). The quality of the smear sampling was highly unsatisfactory in rural units and unsatisfactory in urban units (achievement: 64.2%; 95% CI: 58.2-70.0%, versus 47.3%, 95% CI: 42-52.7%; P < 0.00001). Quality of coverage was unsatisfactory for both regions. Quality of smear processing and timeliness were highly satisfactory for both rural and urban units. RECOMMENDATIONS: Efforts should be directed toward smear quality improvement, especially in rural units. Health care workers who take smears need training programmes and better instruments. They should receive feedback on smear adequacy from the laboratory. Health education is necessary to improve utilization and programme coverage quality.

Adult↗

Angiogenic potential of perivascularly delivered aFGF in a porcine model of chronic myocardial ischemia.

A number of heparin-binding growth factors, including basic (bFGF) and acidic (aFGF) fibroblast growth factors have been shown to promote angiogenesis in vivo. In this study, we employed a sustained-release polymer extravascular delivery system to evaluate the angiogenic efficacy of a novel form of genetically modified aFGF in the setting of chronic myocardial ischemia. Fifteen Yorkshire pigs subjected to Ameroid occluder placement on the left circumflex (LCX) artery were treated with perivascularly administered aFGF in ethylene vinyl acetate (EVAc) polymer (10 micrograms, n = 7) or EVAc alone (controls, n = 8). Seven to nine weeks later, after coronary angiography to document Ameroid-induced coronary occlusion, all animals underwent studies of coronary flow and global and regional left ventricular function. Microsphere-determined coronary flow in the Ameroid-compromised territory was significantly increased in aFGF-treated compared with control animals, and this improvement in perfusion was maintained during ventricular pacing. Left ventricular function studies demonstrated improved global and regional function in aFGF-treated animals. We conclude that local perivascular delivery of genetically modified aFGF results in significant improvement in myocardial flow and regional and global left ventricular function.

Animals↗

Serratia odorifera biogroup I: an emerging pathogen.

Gram-negative bacteremia is a common cause of infection in hospitalized patients. Serratia sepsis is known to cause clinically significant morbidity and mortality. The most common species involved is Serratia marcescens. Clinicians have been uncertain as to the role of Serratia odorifera biogroup 1 as a human pathogen because most isolates have not been associated with invasive disease. In previous publications, 12 cases have been described in which S odorifera biogroup 1 caused sepsis. These observations verify the organism's role as a human pathogen.

Aged↗

Effect of continuous quality improvement analysis on the delivery of primary percutaneous transluminal coronary angioplasty for acute myocardial infarction.

A successful primary percutaneous transluminal coronary angioplasty (PTCA) program requires a learning process whereby the efficiency of the cardiac catheterization laboratory to deliver prompt intervention can be refined. The purpose of this study was to (1) quantify this learning process in terms of shortening the time to reperfusion, (2) examine the changes in strategy that allowed for this, and (3) determine if expedited reperfusion by primary PTCA improved patient outcomes. A database of all primary PTCA procedures was established in February 1, 1994. Continuous quality assurance analysis was performed, and program modifications introduced as needed. Patients were separated into early (group A = February 1, 1994 through January 31, 1995) and late (group B1 = February 1, 1995 through June 31, 1995, and group B2 = July 1, 1995 through December 31, 1995) cohorts. Time intervals to certain treatment landmarks were compared among groups. In-hospital outcomes were tabulated. Fifty-two consecutive patients were included (group A = 19, group B1 = 17, group B2 = 16). Time intervals shortened significantly (group A vs group B1 vs group B2) with the time from hospital presentation to first balloon inflation decreasing progressively (from 205 to 119 to 97 minutes; p <0.001). Most of this decrease was obtained by shortening the time from hospital presentation to xylocaine administration (158 to 85 to 72 minutes; p <0.005), although the time from xylocaine to first balloon inflation also decreased (from 47 to 33 to 24 minutes; p <0.005). Parallel decreases for in-hospital mortality (26% vs 0%; p = 0.004), adverse events (47% vs 18%; p = 0.05), and length of hospital stay (13.3 +/- 13.7 vs 8.4 +/- 4.4 days; p = NS) were demonstrated for groups A versus B1 and B2. A learning effect following initiation of a primary PTCA program is demonstrated in which reperfusion was more rapidly achieved as the result of procedural changes directed by quality improvement analysis with a concurrent improvement in in-hospital outcomes.

Adrenergic beta-Antagonists↗

Percutaneous treatment of protected and unprotected left main coronary stenoses with new devices: immediate angiographic results and intermediate-term follow-up.

OBJECTIVES: We sought to evaluate the immediate angiographic results and intermediate-term follow-up after percutaneous treatment of left main coronary stenoses in the new device era. BACKGROUND: Historically, balloon angioplasty of left main coronary stenoses has been associated with high procedural morbidity and poor long-term results. It is not clear whether new devices are more effective in this anatomic setting. METHODS: Between July 1993 and July 1995, we performed initial left main coronary interventions on 46 patients (mean age 67 +/- 12 years, 26% women). Quantitative angiography was available for 42 of 46 interventions, and clinical follow-up was obtained for all patients at 1 month, 6 months and 1 year after initial revascularization. RESULTS: Most interventions (42 of 46) were performed in patients with "protected" coronary stenoses to the left coronary system owing to the presence of one or more patent left main coronary grafts. Seventy-seven percent of screened patients were deemed unsuitable for repeat coronary artery bypass surgery. Procedures performed included stenting in 73% of patients (alone in 30% and after rotational atherectomy in 43%), rotational atherectomy in 58% (alone in 15% and before stenting in 43%), directional atherectomy in 4% and angioplasty alone in 7%. Initial procedural success was achieved in all interventions, with no deaths, myocardial infarctions (creatine kinase, MB fraction > 50 IU/liter) or emergent bypass surgery. Follow-up data to date (median duration 9 months, range 6 to 19) demonstrate a 98% overall survival rate and a 6-month event-free survival rate of 78% (six target vessel revascularizations [TVRs], four non-TVRs). CONCLUSIONS: Treatment of protected left main coronary artery stenoses can be accomplished safely and effectively with new device technology. Intermediate-term follow-up demonstrates an acceptably low rate of death, myocardial infarction or repeat revascularization at 6 months and 1 year.

Aged↗

Hemodynamic effects of intracoronary VEGF delivery: evidence of tachyphylaxis and NO dependence of response.

Vascular endothelial growth factor (VEGF) has been utilized to improve blood flow in the setting of myocardial or peripheral vascular ischemia. In this investigation we studied the hemodynamic effects of intracoronary VEGF administration. Hemodynamic parameters and Doppler flow wire recordings from the left anterior descending coronary artery were measured after intracoronary infusion of VEGF (1, 10, and 100 micrograms) in 28 intubated pigs. Additional studies were performed using an in vitro isolated microvessel preparation. VEGF produced a highly significant dose-dependent increase in coronary blood flow (maximal 3.51 +/- 0.85-fold) in the absence of significant changes in epicardial artery diameter, a decline in mean arterial pressure (maximal 43%), and a decrease in left ventricular end-diastolic pressure (maximal 52%), all of which could be inhibited by pretreatment with NG-nitro-L-arginine. The increase in coronary flow seen with 10 or 100 micrograms VEGF was significantly greater than the maximal vasodilation achieved with serotonin or nitroglycerin and was equivalent to a maximal adenosine response. In summary, VEGF stimulates nitric oxide (NO)-dependent dilation of coronary microvessels, and repeat administrations of VEGF resulted in rapid development of tachyphylaxis to VEGF as well as serotonin, but not to nitroglycerin or adenosine, which appeared to be secondary to impaired NO production.

Adenosine↗

Basic fibroblast growth factor in a porcine model of chronic myocardial ischemia: a comparison of angiographic, echocardiographic and coronary flow parameters.

Recently, a number of growth factors including basic fibroblast growth factor (bFGF) have been shown to promote angiogenesis in vivo. In this study, we evaluated dose-dependent effect of bFGF administration in the setting of chronic myocardial ischemia. A total of 18 Yorkshire pigs subjected to ameroid occluder placement on the left circumflex artery were randomized to treatment with 10 (n = 6) or 100 microg (n = 5) of bFGF incorporated into heparin-alginate microspheres or inactive control pellets (n = 7). Eight weeks later, all animals underwent angiographic evaluation of collateral development as well as studies of coronary flow and global and regional left ventricular function. Both bFGF groups had significantly higher angiographic collateral index, TIMI flow scores and coronary flow in the ameroid-compromised territory compared with controls. Left ventricular function studies demonstrated improved global and regional function in both fibroblast growth factor groups with significantly better preservation of regional wall motion in high dose (100 microg) bFGF animals. We conclude that local perivascular delivery of bFGF results in significant improvement in myocardial function in the setting of chronic myocardial ischemia.

Animals↗

Stent jail: a minimum-security prison.

Small but significant side branches (particularly those with baseline ostial narrowing) may be further compromised by stent placement within parent vessel segments. Despite the theoretical risks associated with dilating branches in stent jail, the procedure was successfully completed in 84%, with minimal complications (mostly balloon rupture and local dissection) and no cases of balloon entrapment or deterioration of the final result achieved in the parent vessel.

Angioplasty, Balloon, Coronary↗

Percutaneous occlusion of an iatrogenic aortosaphenous vein--coronary vein fistula via retrograde coronary sinus approach.

Inadvertent aortosaphenous vein graft-coronary vein anastomosis during coronary bypass surgery is an uncommon complication. We describe a case of aortosaphenous vein side-to-side anastomosis to an obtuse marginal vein resulting in a large arteriovenous fistula and elective closure, using embolization coils delivered percutaneously via the coronary sinus. The clinical findings, interventional procedure, and follow-up are also presented, with a discussion of alternative techniques used previously to treat iatrogenic aortosaphenous vein graft venous fistulae.

Aged↗

Angiogenesis induced by acidic fibroblast growth factor as an alternative method of revascularization for chronic myocardial ischemia.

BACKGROUND: The effect of periadventitial administration of acidic fibroblast growth factor (FGF) on coronary microvascular reactivity and blood flow was examined in the collateral-dependent and normally perfused myocardium. METHODS: Ameroid constrictors were placed on the proximal left circumflex (LCx) coronary artery in 14 pigs. In seven pigs acidic FGF (10 micrograms) was administered into the perivascular space of the proximal LCx artery by using an ethylene vinyl acetate copolymer slow release device. After 7 to 9 weeks coronary arterial microvessels (70 to 150 microns) were studied in a pressurized (40 mm Hg) no-flow state with video microscopy. RESULTS: Relaxation mediated by beta-adrenoceptors and induced by isoproterenol (p < 0.05), and endothelium-dependent relaxation induced by adenosine 5' diphosphate (ADP) (p < 0.05) of isolated microvessels from the collateral-dependent LCx region were markedly reduced compared with the respective responses of vessels from the normally perfused left anterior descending (LAD) artery region. Relaxation induced by the adenylate cyclase activator forskolin and the guanylate cyclase activator sodium nitroprusside were unaltered. Chronic treatment with acidic FGF normalized responses to isoproterenol (p < 0.001 versus nontreated LCx) and ADP (p < 0.001 versus nontreated LCx) in the collateral-dependent LCx region, whereas responses to forskolin and sodium nitroprusside were not changed. Blood flow in the collateral-dependent LCx region (0.49 +/- 0.24 ml/min/gm) was less than that in the normally perfused LAD region (0.80 +/- 0.24 ml/min/gm, p < 0.05). Treatment with acidic FGF improved perfusion in the LCx region (0.80 +/- 0.06 ml/min/gm, p < 0.05) but did not significantly affect blood flow in the LAD territory (0.89 +/- 0.09 ml/min/gm). CONCLUSIONS: The periadventitial delivery of acidic FGF normalizes vasomotor regulation by beta-adrenergic and endothelium-dependent mechanisms and improves myocardial perfusion to the collateral-dependent myocardium. This may have implications regarding the treatment of patients with severe coronary artery disease who are not ameneable to conventional methods of revascularization.

Adrenergic beta-Agonists↗

Direct vasomotor effects of isoflurane in subepicardial resistance vessels from collateral-dependent and normal coronary circulation of pigs.

BACKGROUND: The purpose of the current investigation was to determine and compare the direct effect of isoflurane on normal resistance coronary arteries and similarly sized coronary arteries in collateral-dependent (CD) circulation. A differential vasomotor effect of isoflurane might contribute to flow redistribution, either adverse or favorable, between normal and CD regions. METHODS: The authors used a swine model of chronic coronary occlusion. Six weeks after ameroid occluder placement around the left circumflex artery, the heart was removed. Myocardial blood flow, measured in vivo before the removal, was lower during rapid atrial pacing in the CD region than in the normally perfused region. These in vivo studies established the existence and location of CD circulation. Subepicardial microvessels, measuring approximately 100 microns, were dissected from both the CD region and the normal region. Either with or without preconstriction of the vessels with the thromboxane analogue U46619 1 microM, direct vasomotor effect of isoflurane was examined in vitro by video microscopy. In addition, vasomotor responses to endothelin-1, the endothelium-dependent dilator adenosine 5' diphosphate, and the endothelium-independent dilator sodium nitroprusside were compared between CD and normal resistance vessels. RESULTS: Isoflurane caused greater concentration-dependent constriction of the normal vessels than of the CD vessels (P < 0.05); this constrictive effect was masked by preconstriction of the vessels. Vasodilation of ADP was less in CD vessels than in normal vessels (P < 0.001), but vasodilation to sodium nitroprusside was not significantly different (P = 0.45). Vasoconstriction to endothelin-1 was greater in CD vessels than in normal vessels (P < 0.01). CONCLUSIONS: The vasoconstrictive effect of isoflurane normally observed in coronary resistance vessels is impaired in resistance vessels that supply a CD area. The basis of this may be related to endothelial dysfunction.

Anesthetics, Inhalation↗

Vascular endothelial growth factor administration in chronic myocardial ischemia.

Vascular endothelial growth factor (VEGF) is a potent mitogen capable of stimulating angiogenesis. We examined the effect of VEGF administration in a model of chronic porcine myocardial ischemia. Nineteen pigs were instrumented with proximal left circumflex coronary artery (LCX) Ameroid constrictors. In eight animals VEGF (2 microgram) with heparin (50 U) was administered extraluminally to the LCX myocardium with an osmotic pump for 4 wk and 11 other animals served as controls. VEGF-treated animals demonstrated higher flow in the LCX territory during both rest and pacing compared with untreated controls (rest: 1.35 +/- 0.1 vs. 0.80 +/- 0.09 ml.min-1.g-1; pacing; 2.01 +/- 0.37 vs. 1.01 +/- 0.07 ml.min-1.g-1, P < 0.05, VEGF vs. controls). The observed improvement in regional coronary flow in VEGF-treated animals resulted in better preservation of endothelium-dependent microvessel relaxation as well as fractional LV shortening in the LCX territory during pacing in the VEGF-treated than in control animals (controls: 7.1 +/ 2.6 vs. 3.6 +/- 2.0%, rest vs. pacing; VEGF: 6.9 +/- 2.9 vs. 6.3 +/- 2.9%, rest vs. pacing). We conclude that VEGF administration in a gradual coronary occlusion model in pigs results in improvement of coronary flow and preservation of regional hemodynamics in the compromised myocardium.

Animals↗