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1.
Transgend Health ; 9(1): 98-103, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38312457

ABSTRACT

Parental support is associated with improved mental health outcomes for gender diverse youth (GDY). Parents often seek guidance from pediatric providers, but few studies explore what actions make GDY feel supported. Using a qualitative analysis of open-ended survey responses, we aimed to identify ways in which GDY want to be supported by their parents or caregivers. Nine key themes were identified, including using affirming language at home and other settings as desired by GDY, seeking education, and aiding in accessing affirming items and care. Findings from this study can help pediatric medical and mental health providers help parents to support their GDY.

2.
Transl Behav Med ; 7(4): 657-666, 2017 12.
Article in English | MEDLINE | ID: mdl-28275976

ABSTRACT

Medically underserved US immigrants are at an increased risk for death from preventable or curable cancers due to economic, cultural, and/or linguistic barriers to medical care. The purpose of this study was to describe the evaluation of the pilot study of the Healthy Eating for Life (HE4L) English as a second language curriculum. The Reach, Effectiveness Adoption, Implementation, Maintenance (RE-AIM) model was used to design a mixed-methods approach to the evaluation of the HE4L curriculum. Successful implementation was dependent upon enthusiastic teacher and manager support of the curriculum, teachers' ability to flexibly apply the curriculum to meet student needs, and researcher provision of curriculum workbooks. HE4L can be implemented successfully in various adult education settings to teach healthy eating behaviors and English language principles. Scale-up of HE4L may depend on the development of an online version of the curriculum to avoid the costs associated with printing and distributing curriculum materials.


Subject(s)
Curriculum , Diet, Healthy , Health Education/methods , Language , Neoplasms/prevention & control , Risk Reduction Behavior , Adolescent , Adult , Aged , Educational Personnel/psychology , Emigrants and Immigrants/education , Focus Groups , Follow-Up Studies , Healthcare Disparities , Humans , Internet , Middle Aged , Program Evaluation , Qualitative Research , Surveys and Questionnaires , Treatment Outcome , Young Adult
3.
J Comp Pathol ; 150(2-3): 345-9, 2014.
Article in English | MEDLINE | ID: mdl-24444818

ABSTRACT

A 10-year-old captive male Siberian tiger (Panthera tigris altaica) presented with acute onset collapse, vomiting and dyspnoea, preceded by a 6-month period of progressive muscle wasting. Following humane destruction, post-mortem examination revealed a large multilobulated mass in the cranial mediastinum, which was diagnosed as a T-lymphocyte-rich thymoma with the aid of immunohistochemistry. Retrospective serology for acetylcholine receptor antibodies (titre 3.90 nmol/l) confirmed a diagnosis of thymoma-associated myasthenia gravis. Thymomas are reported rarely in wild carnivores, but when detected they appear to be similar in morphology to those seen in domestic carnivores and may also be accompanied by paraneoplastic syndromes. The clinical signs of myasthenia gravis in the tiger were consistent with those reported in cats and dogs and the condition is proposed as an important differential diagnosis for generalized weakness in captive Felidae.


Subject(s)
Myasthenia Gravis/veterinary , T-Lymphocytes/pathology , Thymoma/veterinary , Thymus Neoplasms/veterinary , Tigers , Animals , Male , Myasthenia Gravis/pathology , Thymoma/pathology , Thymus Neoplasms/pathology
4.
Arch Environ Contam Toxicol ; 52(1): 97-103, 2007 Jan.
Article in English | MEDLINE | ID: mdl-17061050

ABSTRACT

The purpose of this study was to determine if wetlands influence mercury concentrations in brook trout (Salvelinus fontinalis), benthic macroinvertebrates, and stream water. On September 26, 2005, water samples, benthic macroinvertebrates, and brook trout were collected from four streams in western Maryland under low-flow conditions. Water samples were also collected in these four streams under high-flow conditions in January 2006. The watersheds of Blue Lick and Monroe Run did not contain wetlands, but the watersheds of the Upper Savage River (3% of upstream area) and Little Savage River (7% of upstream area) contained wetlands. We found significantly (p = 0.05) higher average total mercury concentration in brook trout from Little Savage River (129 +/- 54 ng g(-1)); intermediate concentrations (66 +/- 19 ng g(-1)) in brook trout from Upper Savage River; and lowest concentrations in brook trout from Blue Lick (28 +/- 11 ng g(-1)) and Monroe Run (23 +/- 19 ng g(-1)). Brook trout in all streams accumulated mercury at the same rate over their lifetimes, but the youngest fish had significantly different mercury concentrations (Little Savage > Upper Savage > Blue Lick = Monroe Run), which may be due to differences in mercury concentrations in the eggs or food for the fry. Mercury concentrations in brook trout were not consistent with mercury concentrations in stream water and benthic macroinvertebrates. The Little Savage River had significantly higher total and methylmercury concentrations in stream water, but mercury concentrations in the other streams and in the benthic macroinvertebrates were not significantly different among streams. The unusually high methylmercury concentrations (0.5 to 2.1 ng L(-1)) in the Little Savage River may have been caused by production of methylmercury in the pools. The relatively low methylmercury concentrations in the Upper Savage River may be caused by a mercury concentration gradient downstream of the wetland.


Subject(s)
Fresh Water/chemistry , Invertebrates/chemistry , Mercury/analysis , Trout , Water Pollutants, Chemical/analysis , Wetlands , Animals , Environmental Monitoring/methods , Maryland , Methylmercury Compounds/analysis
5.
Ann Thorac Surg ; 72(2): 548-53; discussion 553-4, 2001 Aug.
Article in English | MEDLINE | ID: mdl-11515896

ABSTRACT

BACKGROUND: Angiotensin-converting enzyme (ACE) inhibitors differ in their ability to inhibit tissue ACE. This study was, therefore, undertaken to determine whether high tissue affinity ACE inhibitors would improve endothelial function and thereby decrease tissue necrosis during ischemia. METHODS: In a porcine model, the second and third diagonal vessels were occluded for 90 minutes, followed by 45 minutes of cardioplegic arrest and 180 minutes of reperfusion. During the period of coronary occlusion, 10 pigs received enalaprilat (low affinity tissue ACE inhibitor), 0.05 mg/kg intravenously, 10 received quinaprilat (high affinity tissue ACE inhibitor), 10 mg intravenously, and 10 others received no ACE inhibitor. RESULTS: Wall motion scores (4, normal, to -1, dyskinesia) were higher in animals treated with ACE inhibitors (3.20+/-0.15 SE enalaprilat versus 3.08+/-0.23 quinaprilat versus 1.52+/-0.07 no ACE; both p < 0.0001 from no ACE). Endothelial-dependent relaxation to bradykinin was best preserved in the quinaprilat-treated hearts (32.1%+/-7.6% enalaprilat versus 65.8%+/-12.6% quinaprilat versus 30.6%+/-10.7% no ACE; p < 0.0001 from no ACE; p < 0.005 from enalaprilat). This was associated with a greater reduction in infarct size: area necrosis/area risk 24.3%+/-0.8% enalaprilat (p < 0.0001 from no ACE) versus 14.3%+/-3.2% quinaprilat (p < 0.0001 from no ACE; p < 0.005 from enalaprilat) versus 40.0%+/-1.7% no ACE. CONCLUSIONS: ACE inhibitors with higher affinity to tissue ACE result in better preservation of endothelial function and less tissue necrosis during coronary revascularization.


Subject(s)
Angiotensin-Converting Enzyme Inhibitors/pharmacology , Enalaprilat/pharmacology , Endothelium, Vascular/drug effects , Isoquinolines/pharmacology , Myocardial Infarction/pathology , Myocardial Reperfusion Injury/pathology , Tetrahydroisoquinolines , Animals , Infusions, Intravenous , Myocardial Contraction/drug effects , Myocardium/pathology , Necrosis , Swine
6.
J Biol Inorg Chem ; 6(5-6): 523-33, 2001 Jun.
Article in English | MEDLINE | ID: mdl-11472016

ABSTRACT

The bioI gene has been sub-cloned and over-expressed in Escherichia coli, and the protein purified to homogeneity. The protein is a cytochrome P450, as indicated by its visible spectrum (low-spin haem iron Soret band at 419 nm) and by the characteristic carbon monoxide-induced shift of the Soret band to 448 nm in the reduced form. N-terminal amino acid sequencing and mass spectrometry indicate that the initiator methionine is removed from cytochrome P450 BioI and that the relative molecular mass is 44,732 Da, consistent with that deduced from the gene sequence. SDS-PAGE indicates that the protein is homogeneous after column chromatography on DE-52 and hydroxyapatite, followed by FPLC on a quaternary ammonium ion-exchange column (Q-Sepharose). The purified protein is of mixed spin-state by both electronic spectroscopy and by electron paramagnetic resonance [g values=2.41, 2.24 and 1.97/1.91 (low-spin) and 8.13, 5.92 and 3.47 (high-spin)]. Magnetic circular dichroism and electron paramagnetic resonance studies indicate that P450 BioI has a cysteine-ligated b-type haem iron and the near-IR magnetic circular dichroism band suggests strongly that the sixth ligand bound to the haem iron is water. Resonance Raman spectroscopy identifies vibrational signals typical of cytochrome P450, notably the oxidation state marker v4 at 1,373 cm(-1) (indicating ferric P450 haem) and the splitting of the spin-state marker v3 into two components (1,503 cm(-1) and 1,488 cm(-1)), indicating cytochrome P450 BioI to be a mixture of high- and low-spin forms. Fatty acids were found to bind to cytochrome P450 BioI, with myristic acid (Kd=4.18+/-0.26 microM) and pentadecanoic acid (Kd=3.58+/-0.54 microM) having highest affinity. The fatty acid analogue inhibitor 12-imidazolyldodecanoic acid bound extremely tightly (Kd<1 microM), again indicating strong affinity for fatty acid chains in the P450 active site. Catalytic activity was demonstrated by reconstituting the P450 with either a soluble form of human cytochrome P450 reductase, or a Bacillus subtilis ferredoxin and E. coli ferredoxin reductase. Substrate hydroxylation at the omega-terminal position was demonstrated by turnover of the chromophoric fatty acid para-nitrophenoxydodecanoic acid, and by separation of product from the reaction of P450 BioI with myristic acid.


Subject(s)
Bacillus subtilis/metabolism , Bacterial Proteins/chemistry , Bacterial Proteins/metabolism , Fatty Acids/chemistry , Bacterial Proteins/genetics , Bacterial Proteins/isolation & purification , Biotin/biosynthesis , Circular Dichroism , Cloning, Molecular , Cytochrome P-450 Enzyme System/metabolism , Electron Spin Resonance Spectroscopy , Fatty Acids/metabolism , Hydroxylation , Imidazoles/chemistry , Imidazoles/metabolism , Myristic Acid/metabolism , Sequence Analysis, Protein , Spectrophotometry, Ultraviolet , Spectrum Analysis, Raman , Substrate Specificity
7.
J Nerv Ment Dis ; 189(4): 229-37, 2001 Apr.
Article in English | MEDLINE | ID: mdl-11339318

ABSTRACT

Positive change was demonstrated on a number of self-report scales administered to 129 adolescents at a hospital-based substance abuse program, of whom 72 were posttested after 8 weeks. Female subjects showed change on more measures than male subjects, and a greater number of female subjects went from the clinical to subclinical range. Based on number of sessions attended, subjects were grouped by "dose" into either "hi-attenders" or "lo-attenders." A Trials (pretest/posttest) x Dose interaction revealed significant reduction in drug use at posttest for hi-attenders who were initially heavier users. Multiple regression analyses determined how well "comorbidity" predicted attendance and change in drug use. Although comorbidity failed to predict attendance consistently, male subjects who reported more internalizing symptomatology reduced their drug use to a greater extent than those low on this dimension, and female subjects who initially reported experiencing more family problems became more self-efficacious about future drug avoidance.


Subject(s)
Mental Disorders/therapy , Outpatient Clinics, Hospital , Psychotherapy , Substance-Related Disorders/therapy , Adolescent , Child , Cognitive Behavioral Therapy , Comorbidity , Diagnosis, Dual (Psychiatry) , Family Relations , Female , Humans , Male , Mental Disorders/diagnosis , Mental Disorders/epidemiology , Patient Dropouts , Personality Inventory/statistics & numerical data , Psychiatric Status Rating Scales/statistics & numerical data , Severity of Illness Index , Sex Factors , Substance Abuse Treatment Centers , Substance-Related Disorders/diagnosis , Substance-Related Disorders/epidemiology , Treatment Outcome
8.
Biochem Soc Trans ; 29(Pt 2): 147-52, 2001 May.
Article in English | MEDLINE | ID: mdl-11356143

ABSTRACT

The nitric oxide synthases (NOSs) are dimeric flavocytochromes consisting of an oxygenase domain with cytochrome P450-like Cys-ligated haem, coupled to a diflavin reductase domain, which is related to cytochrome P450 reductase. The NOSs catalyse the sequential mono-oxygenation of arginine to N-hydroxyarginine and then to citrulline and NO. The constitutive NOS isoforms (cNOSs) are regulated by calmodulin (CaM), which binds at elevated concentrations of free Ca(2+), whereas the inducible isoform binds CaM irreversibly. One of the main structural differences between the constitutive and inducible isoforms is an insert of 40-50 amino acids in the FMN-binding domain of the cNOSs. Deletion of the insert in rat neuronal NOS (nNOS) led to a mutant enzyme which binds CaM at lower Ca(2+) concentrations and which retains activity in the absence of CaM. In order to resolve the mechanism of action of CaM activation we determined reduction potentials for the FMN and FAD cofactors of rat nNOS in the presence and absence of CaM using a recombinant form of the reductase domain. The results indicate that CaM binding does not modulate the reduction potentials of the flavins, but appears to control electron transfer primarily via a large structural rearrangement. We also report the creation of chimaeric enzymes in which the reductase domains of nNOS and flavocytochrome P450 BM3 (Bacillus megaterium III) have been exchanged. Despite its very different flavin redox potentials, the BM3 reductase domain was able to support low levels of CaM-dependent NO synthesis, whereas the NOS reductase domain did not effectively substitute for that of cytochrome P450 BM3.


Subject(s)
Bacterial Proteins , Electron Transport , Neurons/enzymology , Nitric Oxide Synthase/metabolism , Amino Acid Substitution/genetics , Animals , Bacillus megaterium/enzymology , Bacillus megaterium/genetics , Calmodulin/metabolism , Cytochrome P-450 Enzyme System/chemistry , Cytochrome P-450 Enzyme System/genetics , Cytochrome P-450 Enzyme System/metabolism , Flavin Mononucleotide/metabolism , Flavin-Adenine Dinucleotide/metabolism , Kinetics , Mixed Function Oxygenases/chemistry , Mixed Function Oxygenases/genetics , Mixed Function Oxygenases/metabolism , NADP/metabolism , NADPH-Ferrihemoprotein Reductase , Nerve Tissue Proteins/antagonists & inhibitors , Nerve Tissue Proteins/chemistry , Nerve Tissue Proteins/genetics , Nerve Tissue Proteins/metabolism , Nitric Oxide/metabolism , Nitric Oxide Synthase/antagonists & inhibitors , Nitric Oxide Synthase/chemistry , Nitric Oxide Synthase/genetics , Nitric Oxide Synthase Type I , Oxidation-Reduction , Protein Binding , Protein Structure, Tertiary , Rabbits , Rats , Recombinant Fusion Proteins/antagonists & inhibitors , Recombinant Fusion Proteins/chemistry , Recombinant Fusion Proteins/genetics , Recombinant Fusion Proteins/metabolism , Sequence Deletion/genetics , Structure-Activity Relationship
10.
Biochemistry ; 38(50): 16413-8, 1999 Dec 14.
Article in English | MEDLINE | ID: mdl-10600101

ABSTRACT

Midpoint reduction potentials for the flavin cofactors in the reductase domain of rat neuronal nitric oxide synthase (nNOS) in calmodulin (CaM)-free and -bound forms have been determined by direct anaerobic titration. In the CaM-free form, the FMN potentials are -49 +/- 5 mV (oxidized/semiquinone) -274 +/- 5 mV (semiquinone/reduced). The corresponding FAD potentials are -232 +/- 7, and -280 +/- 6 mV. The data indicate that each flavin can exist as a blue (neutral) semiquinone. The accumulation of blue semiquinone on the FMN is considerably higher than seen on the FAD due to the much larger separation (225 mV) of its two potentials (cf. 48 mV for FAD). For the CaM-bound form of the protein, the midpoint potentials are essentially identical: there is a small alteration in the FMN oxidized/semiquinone potential (-30 +/- 4 mV); the other three potentials are unaffected. The heme midpoint potentials for nNOS [-239 mV, L-Arg-free; -220 mV, L-Arg-bound; Presta, A., Weber-Main, A. M., Stankovich, M. T., and Stuehr, D. J. (1998) J. Am. Chem. Soc. 120, 9460-9465] are poised such that electron transfer from flavin domain is thermodynamically feasible. Clearly, CaM binding is necessary in eliciting conformational changes that enhance flavin to flavin and flavin to heme electron transfers rather than causing a change in the driving force.


Subject(s)
Flavin Mononucleotide/chemistry , Flavin-Adenine Dinucleotide/chemistry , Flavins/chemistry , Nerve Tissue Proteins/chemistry , Nitric Oxide Synthase/chemistry , Animals , Binding Sites , Calmodulin/chemistry , Calmodulin/metabolism , Flavin Mononucleotide/metabolism , Flavin-Adenine Dinucleotide/metabolism , Flavins/metabolism , Nerve Tissue Proteins/metabolism , Nitric Oxide Synthase/metabolism , Nitric Oxide Synthase Type I , Oxidation-Reduction , Potentiometry/methods , Rabbits , Rats
11.
Circulation ; 100(13): 1438-42, 1999 Sep 28.
Article in English | MEDLINE | ID: mdl-10500046

ABSTRACT

BACKGROUND: Activation of complement during revascularization of ischemic myocardium accentuates myocardial dysfunction. Soluble human complement receptor type 1 (sCR1) is a potent inhibitor of complement, as are heparin-bonded (HB) cardiopulmonary bypass (CPB) circuits. This study sought to determine whether total complement inhibition with the combination of sCR1 and HB-CPB limits damage during the revascularization of ischemic myocardium. METHODS AND RESULTS: In 40 pigs, the second and third diagonal coronary arteries were occluded for 90 minutes, followed by 45 minutes of cardioplegic arrest and 180 minutes of reperfusion. In 10 pigs, sCR1 (10 mg/kg) was infused 5 minutes after the onset of coronary occlusion (sCR1), 10 received HB-CPB only (HB-CPB), 10 received sCR1 and HB-CPB (sCR1+HB), and 10 received neither sCR1 or HB-CPB (unmodified). Addition of sCR1 to the HB group resulted in less myocardial tissue acidosis (DeltapH = -0.72+/-0.03 for unmodified; -0.46+/-0.05 for HB; -0.18+/-0.04 for sCR1; -0.13+/-0.01 for sCR1+HB), better recovery of wall motion scores (4 = normal to -1 = dyskinesia; 1.67+/-0.17 for unmodified; 2.80+/-0.08 for HB; 3.35+/-0.10 for sCR1; 3.59+/-0.08 for sCR1+HB), less lung water accumulation (5.46+/-0.28% for unmodified; 2.39+/-0.34% for HB; 1.22+/-0.07% for sCR1; 1.24+/-0.13% for sCR1+HB), and smaller infarct size (area necrosis/area risk = 44.6+/-0.7% for unmodified; 33.2+/-1.9% for HB; 19.0+/-2.4% for sCR1; 20+/-1.0% for sCR1+HB) (P<0.05 versus unmodified; P<0.05 versus unmodified and HB groups). CONCLUSIONS: Total complement inhibition with sCR1 and sCR1+HB circuits optimizes recovery during the revascularization of ischemic myocardium.


Subject(s)
Anticoagulants/pharmacology , Cardiopulmonary Bypass , Complement Inactivator Proteins/pharmacology , Heparin/pharmacology , Myocardial Ischemia/pathology , Myocardial Reperfusion Injury/pathology , Receptors, Complement/physiology , Animals , Body Water/metabolism , Complement System Proteins/analysis , Heart/physiopathology , Humans , Hydrogen-Ion Concentration , Lung/metabolism , Myocardial Infarction/pathology , Myocardial Ischemia/blood , Myocardial Ischemia/physiopathology , Myocardial Reperfusion Injury/blood , Myocardial Reperfusion Injury/physiopathology , Myocardium/metabolism , Solubility , Swine
12.
Ann Thorac Surg ; 67(2): 446-9, 1999 Feb.
Article in English | MEDLINE | ID: mdl-10197668

ABSTRACT

BACKGROUND: This experimental study sought to determine whether heparin-bonding of intraaortic balloons (IAB) would decrease the incidence of arterial thrombosis in the absence of systemic heparinization. METHODS: In 25 adult pigs, a 9F, 40-mL IAB was inserted into the femoral artery and positioned just below the takeoff of the left subclavian artery for 9 hours. Five animals received systemic heparin, 10 animals had no heparin, and another 10 animals received no heparin but the IAB was heparin-bonded (Duraflo II). Thrombus formation was assessed using a numerical scoring system (0 = no thrombosis to 3 = thrombus >5 cm or evidence of luminal compromise). RESULTS: Animals receiving heparin and heparin-bonded IAB had no thrombus formation around the IAB (mean +/- SE; 0 +/- 0.00 heparin versus 1.55 +/- 0.29 no heparin versus 0 +/- 0.00 heparin-bonded; p < 0.005), at the insertion site (0 +/- 0.00 heparin versus 1.55 +/- 0.29 no heparin versus 0 +/- 0.0 heparin-bonded; p < 0.005), and in the distal femoral artery (0 +/- 0.00 heparin versus 2.00 +/- 0.23 no heparin versus 0 +/- 0.00 heparin-bonded; p < 0.005). CONCLUSIONS: Heparin-bonding of the IAB significantly decreases thrombus formation in the absence of systemic heparinization.


Subject(s)
Coated Materials, Biocompatible , Heparin , Intra-Aortic Balloon Pumping/instrumentation , Thrombosis/prevention & control , Animals , Equipment Design , Heparin/administration & dosage , Swine , Thrombosis/blood , Whole Blood Coagulation Time
14.
Clin Lung Cancer ; 1(2): 110-7; discussion 118-9, 1999 Nov.
Article in English | MEDLINE | ID: mdl-14733657

ABSTRACT

It has been known for some time that participation in support groups is beneficial for most cancer survivors. Despite this, and even though lung cancer causes more deaths than breast, prostate, and colorectal cancers combined, the number of support groups formed for lung cancer survivors is surprisingly very small. In an effort to understand the lack of lung cancer specific support groups, the Alliance for Lung Cancer Advocacy, Support, and Education (ALCASE) conducted a survey of the facilitators of the lung cancer support groups then known to be in existence in the United States, in addition to a follow-up focus group with the facilitators via teleconference. The results of the survey and the focus group provide a very preliminary look at the value to lung cancer survivors of participating in support groups organized specifically for them. However, much more research is required, not only with the participants of these groups, but also with lung cancer survivors who do not participate, to fully gauge the effects of support group participation on the progress of their disease and on their quality of life.

15.
Ann Thorac Surg ; 66(2): 487-92, 1998 Aug.
Article in English | MEDLINE | ID: mdl-9725390

ABSTRACT

BACKGROUND: This experimental study was undertaken to determine whether using angiotensin-converting enzyme inhibitors during surgical revascularization of acutely ischemic myocardium would improve wall motion and limit infarct size. METHODS: Twenty pigs underwent 90 minutes of occlusion of the second and third diagonal arteries followed by 45 minutes of cardioplegic arrest and 180 minutes of reperfusion. In 10 animals, the angiotensin-converting enzyme inhibitor enalaprilat (0.05 mg/kg) was infused intravenously during coronary occlusion; 10 other animals received no angiotensin-converting enzyme inhibitors. Ischemic damage was assessed by the number of cardioversions required for ventricular tachycardia or fibrillation; wall motion scores using echocardiography (4=normal to -1=dyskinesia); and infarct size using histochemical staining. Epicardial coronary artery vasomotor function was assessed using standard organ chamber methodology. RESULTS: Enalaprilat-treated hearts had the least amount of ventricular irritability (0.84+/-0.24 versus 2.77+/-0.22 cardioversions; p < 0.01), the best recovery of wall motion score (3.20+/-0.15 versus 1.52+/-0.07; p < 0.0001), and the lowest infarct size (22.6%+/-1.4% versus 37.7%+/-3.0%; p < 0.001). Endothelium-independent relaxation was preserved in all hearts; however, endothelium-dependent relaxation was impaired in both groups. CONCLUSIONS: Angiotensin-converting enzyme inhibitors reduce myocardial damage during surgical revascularization of acutely ischemic myocardium.


Subject(s)
Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Enalaprilat/therapeutic use , Myocardial Revascularization/methods , Animals , Blood Pressure , Coronary Vessels/physiology , Echocardiography , Electric Countershock , Enalaprilat/administration & dosage , Heart Arrest, Induced , Heart Rate , Infusions, Intravenous , Swine , Tachycardia, Ventricular/therapy , Vasomotor System/physiology , Ventricular Fibrillation/therapy
16.
Ann Thorac Surg ; 65(4): 973-7, 1998 Apr.
Article in English | MEDLINE | ID: mdl-9564912

ABSTRACT

BACKGROUND: This study was undertaken to determine whether suppression of complement activation with soluble human complement receptor type I reduces myocardial damage during the revascularization of ischemic myocardium. METHODS: In 20 pigs, the second and third diagonal coronary arteries were occluded for 90 minutes, followed by 45 minutes of cardioplegic arrest and 180 minutes of reperfusion. In 10 pigs, soluble human complement receptor type I (10 mg/kg) was infused over 30 minutes before the period of coronary occlusion; 10 other pigs received no soluble human complement receptor type I. Complement activation was measured by total hemolytic complement activity (expressed as a percentage of preischemic values). Ischemic damage was assessed by changes in myocardial tissue pH, wall motion scores (range, 4=normal to -1=dyskinesia), and infarct size (area of necrosis versus area at risk). RESULTS: After 180 minutes of reperfusion, hearts treated with soluble human complement receptor type I had significantly less complement activation than nontreated hearts (1.1%+/-0.09% versus 7.8%+/-0.04%, respectively; p < 0.002), less myocardial acidosis (-0.41+/-0.03 versus -0.72+/-0.03, respectively; p < 0.0001), higher wall motion scores (3.1+/-0.09 versus 1.67+/-0.16, respectively; p < 0.0001), and smaller infarct size (24.6%+/-2.0% versus 41%+/-1.3%, respectively; p < 0.0001). CONCLUSIONS: Complement inhibition with soluble human complement receptor type I significantly limits ischemic damage during the revascularization of acutely ischemic myocardium.


Subject(s)
Complement Inactivator Proteins/therapeutic use , Myocardial Ischemia/therapy , Myocardial Reperfusion Injury/prevention & control , Myocardial Reperfusion , Receptors, Complement/therapeutic use , Acidosis/etiology , Acidosis/physiopathology , Animals , Cardiomyopathies/etiology , Cardiomyopathies/physiopathology , Complement Activation/drug effects , Complement Inactivator Proteins/administration & dosage , Coronary Disease/physiopathology , Heart Arrest, Induced , Hemolysis , Humans , Hydrogen-Ion Concentration , Infusions, Intravenous , Myocardial Contraction/drug effects , Myocardial Ischemia/pathology , Myocardial Ischemia/physiopathology , Myocardium/pathology , Necrosis , Random Allocation , Receptors, Complement/administration & dosage , Swine
17.
Ann Thorac Surg ; 63(6): 1701-5, 1997 Jun.
Article in English | MEDLINE | ID: mdl-9205170

ABSTRACT

BACKGROUND: Heparin-bonded cardiopulmonary bypass circuits reduce complement activation, but their effect on myocardial function is unknown. This study was undertaken to determine whether heparin-bonded circuits reduce myocardial damage during acute surgical revascularization. METHODS: In 16 pigs, the second and third diagonal vessels were occluded with snares for 90 minutes followed by 45 minutes of cardioplegic arrest and 180 minutes of reperfusion with the snares released. During the period of coronary occlusion, all animals were placed on percutaneous bypass followed by standard cardiopulmonary bypass during the periods of cardioplegic arrest and reperfusion. In 8 pigs, heparin-bonded circuits were used, whereas 8 other pigs received nonbonded circuits. RESULTS: Animals treated with heparin-bonded circuits had the best preservation of wall motion scores (3.5 +/- 0.3 versus 2.3 +/- 0.2; 4 = normal to -1 = dyskinesis; p < 0.05), least tissue acidosis (change in pH = -0.31 +/- 0.02 versus -0.64 +/- 0.08; p < 0.05), smallest increase in lung H2O (1.7% +/- 0.7% versus 6.1% +/- .5%; p < 0.05), and the lowest area of necrosis/area of risk (20.3% +/- 2.2% versus 40.4% +/- 1.6%; p < 0.05). CONCLUSIONS: We conclude that heparin-bonded circuits significantly decrease myocardial ischemic damage during acute surgical revascularization.


Subject(s)
Cardiopulmonary Bypass/methods , Heparin/administration & dosage , Myocardial Ischemia/prevention & control , Acid-Base Equilibrium/physiology , Animals , Biocompatible Materials , Body Water/physiology , Echocardiography , Electrocardiography , Hemodynamics/physiology , Lung/physiopathology , Myocardial Contraction/physiology , Random Allocation , Swine
18.
J Vasc Surg ; 24(6): 984-96; discussion 996-7, 1996 Dec.
Article in English | MEDLINE | ID: mdl-8976352

ABSTRACT

PURPOSE: Although axillobifemoral bypass procedures have a lower mortality rate than aortobifemoral bypass procedures, they are limited by decreased patency, moderate hemodynamic improvement, and the need for general anesthesia. This report describes an alternative approach to bilateral aortoiliac occlusive disease using unilateral endovascular aortofemoral bypass procedures in combination with standard femorofemoral reconstructions. METHODS: Seven patients who had bilateral critical ischemia and tissue necrosis in association with severe comorbid medical illnesses underwent implantation of unilateral aortofemoral endovascular grafts, which were inserted into predilated, recanalized iliac arteries. The proximal end of the endovascular graft was fixed to the distal aorta or common iliac artery with a Palmaz stent. The distal end of the graft was suture-anastomosed to the ipsilateral patent outflow vessel, and a femorofemoral bypass procedure was then performed. RESULTS: All endovascular grafts were successfully inserted through five occluded and two diffusely stenotic iliac arteries under either local (1), epidural (5), or general anesthesia (1). The mean thigh pulse volume recording amplitudes increased from 9 +/- 3 mm to 30 +/- 7 mm and from 6 +/- 2 mm to 26 +/- 4 mm ipsilateral and contralateral to the aortofemoral graft insertion, respectively. In all cases the symptoms completely resolved. Procedural complications were limited to one local wound hematoma. No graft thromboses occurred during follow-up to 28 months (mean, 17 months). CONCLUSIONS: Endovascular iliac grafts in combination with standard femorofemoral bypass grafts may be an effective alternative to axillobifemoral bypass in high-risk patients who have diffuse aortoiliac occlusive disease, particularly when bilateral axillary-subclavian disease is present.


Subject(s)
Aorta, Abdominal/surgery , Arterial Occlusive Diseases/surgery , Blood Vessel Prosthesis , Femoral Artery/surgery , Iliac Artery/surgery , Ischemia/surgery , Leg/blood supply , Aged , Comorbidity , Female , Follow-Up Studies , Humans , Male , Risk Factors , Time Factors , Treatment Outcome
19.
Ann Thorac Surg ; 62(1): 9-15, 1996 Jul.
Article in English | MEDLINE | ID: mdl-8678691

ABSTRACT

BACKGROUND: Despite the proven efficacy of pressure-controlled intermittent coronary sinus obstruction (PICSO) and synchronized retrograde perfusion (SRP) in salvaging ischemic myocardium, wide application of these coronary sinus (CS) retroperfusion techniques has been limited by concerns about their safety and complexity and in particular the need for repeated occlusion of the CS with a balloon. To address these concerns a simplified retroperfusion technique (SR) was developed that continuously infuses superior vena caval blood at 7 mL/min into the CS catheter without balloon occlusion. METHODS: Thirty pigs underwent 90 minutes of ischemia imposed by snaring the two largest diagonal branches of the left anterior descending artery and were randomized to one of five treatment groups: One group received no retroperfusion (control). Three groups had immediate (Im) institution of PICSO, SRP, or SR. In a final group, an initial 60 minutes of ischemia was followed by 30 minutes of delayed SR with superior vena caval blood. All animals were then placed on cardiopulmonary bypass and, after a 60-minute cardioplegic arrest, the coronary artery obstructions were removed, to simulate surgical revascularization. This was followed by 3 hours of reperfusion. The area of myocardium at risk and the area of infarction were determined by methylene blue and triphenyltetrazolium chloride staining with planimetric quantification. RESULTS: Results are reported as mean +/- standard deviation. The area of the left ventricle at risk for infarction was similar in all the treatment groups and represented 22.3% +/- 4.1% of the left ventricular mass. The area of infarction after 3 hours of reperfusion was 48.5% +/- 11.0% for the control group, 26.8% +/- 7.3% for Im-PICSO, 24.9% +/- 4.8% for Im-SRP, 22.4% +/- 6.6% for Im-SR, and 27.7% +/- 7.2% for delayed SR (p < 0.01 for each group versus control). The mean CS pressure (in mm Hg) during treatment was 6.3 +/- 1.7 for the control group, 25.7 +/- 4.5 for Im-PICSO, 22.8 +/- 3.7 for Im-SRP, 5.0 +/- 1.5 for Im-SR, and 6.3 +/- 2.1 for delayed SR (p < 0.01 for Im-PICSO and Im-SRP versus control). CONCLUSIONS: The simplified retroperfusion technique is as effective as PICSO and SRP in salvaging ischemic myocardium, but is considerably simpler. The simplified retroperfusion technique is inherently safer because of the lower CS pressures imposed by low flows and the lack of CS balloon obstruction. The efficacy of delayed SR has profound implications on possible mechanisms of ischemic myocardial salvage. Further investigation is warranted.


Subject(s)
Myocardial Reperfusion Injury/prevention & control , Myocardial Reperfusion/methods , Animals , Blood Pressure/physiology , Cardiopulmonary Bypass , Coronary Circulation/physiology , Coronary Disease/physiopathology , Coronary Vessels , Electrocardiography , Heart Arrest, Induced , Swine , Time Factors , Vena Cava, Superior
20.
J Exp Psychol Anim Behav Process ; 22(1): 87-104, 1996 Jan.
Article in English | MEDLINE | ID: mdl-8568499

ABSTRACT

Four experiments using barpress conditioned suppression in rats found that tone evoked more freezing (immobility) than did light. Still, tone and light appeared to have similar conditioned value as assessed by suppression in Experiments 1, 2, and 3, and by blocking, second-order conditioning, and overconditioning assays in Experiments 1, 2, and 3, respectively. Experiment 4 arranged for tone to evoke less suppression than light but more freezing. Results suggest that in fear conditioning, the nature of the conditioned stimulus affects the form of conditioned responding (strong vs. weak freezing). This conclusion extends one drawn by P. C. Holland (1977) on the basis of his work in appetitive conditioning.


Subject(s)
Conditioning, Classical , Fear , Animals , Appetitive Behavior , Behavior, Animal , Extinction, Psychological , Female , Male , Rats , Reinforcement, Psychology
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