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Biomedical subjects

J Mickelson

Publications and source records attributed to J Mickelson.

11 recordsLinked to original sources

First comprehensive low-density horse linkage map based on two 3-generation, full-sibling, cross-bred horse reference families.

Two 3-generation full-sibling reference families have been produced and form a unique resource for genetic linkage mapping studies in the horse. The F(2) generations, now comprising 61 individuals, consist of 28- to 32-day-old embryos removed nonsurgically from two pairs of identical twin mares. The same stallion sired all F(2)s such that the two full-sibling families are half-sibling with respect to each other. The families are crossbred to maximize levels of heterozygosity and include Arabian, Thoroughbred, Welsh Cob, and Icelandic Horse breeds. Milligram quantities of DNA have been isolated from each embryo and from blood samples of the parents and grandparents. The families have been genotyped with 353 equine microsatellites and 6 biallelic markers, and 42 linkage groups were formed. In addition, the physical location of 85 of the markers is known, and this has allowed 37 linkage groups to be anchored to the physical map. The inclusion of dams in the genotyping analysis has allowed the generation of a genetic map of the X chromosome. Markers have been assigned to all 31 autosomes and the X chromosome. The average interval between markers on the map is 10.5 cM, and the linkage groups collectively span 1780 cM. The results demonstrate the benefits for horse linkage mapping studies of genotyping on these unique full-sibling families, which comprise relatively few individuals, by the generation of a comprehensive low-density map of the horse genome.

Animals↗

Supine bicycle versus post-treadmill exercise echocardiography in the detection of myocardial ischemia: a randomized single-blind crossover trial.

OBJECTIVES: We sought to determine the comparative accuracy of supine bicycle exercise echocardiography (SBE) and posttreadmill exercise echocardiography (TME) in detecting myocardial ischemia in patients with known or suspected coronary artery disease (CAD). BACKGROUND: Supine bicycle echocardiography and TME have been used for evaluation of CAD. However, the comparative accuracy of these modalities in the detection of ischemia in the same patients is not known. METHODS: Seventy-four patients (age 59 +/- 9 years [mean +/- SD]) referred for evaluation of coronary disease underwent SBE (starting at 25 to 50 W with 25-W increment every 3 min) and post-TME (Bruce protocol) in a random sequence. Digitized images at baseline and maximal exercise were interpreted in a random and blinded fashion. RESULTS: Maximal heart rate was higher during TME, whereas systolic blood pressure was higher during SBE, resulting in a similar double product. At quantitative angiography (n = 67), 57 patients had coronary stenosis (>50%). During SBE, ischemia was detected in 47 patients compared with 38 patients by TME (p < 0.001). Wall motion score index at maximal exercise was higher with SBE than with TME (1.48 +/- 0.51 vs. 1.38 +/- 0.43; p < 0.001). The extent of myocardial ischemia (number of ischemic segments) was higher during SBE compared with TME (3.3 +/- 3.4 vs. 2.3 +/- 2.9 segments; p = 0.004), whereas severity of abnormal wall motion was similar. The sensitivity of SBE and TME for CAD was 82% and 75% with a specificity of 80% and 90%, respectively. Image quality was similar with both techniques. Patients and sonographers favored SBE over TME. CONCLUSIONS: During SBE and TME exercise, patients achieve a similar double product. During SBE, however, the detection of ischemia is more frequent and more extensive which, along with patient and sonographer preference, makes supine bicycle exercise a valuable stress echocardiographic modality.

Adult↗

Use of bare-mounted Palmaz-Schatz stents employing the stent saddle technique on the delivery balloon: a single center experience.

The major limitations of the Palmaz-Schatz stent stem from the design of its stent delivery system (SDS). The SDS is bulky and has poor trackability in lesions with proximal tortuosity and/or vessel calcification. The use of bare-mounted Palmaz-Schatz stents on low profile balloons represents an alternate approach for lesions that are not accessible for stenting with the SDS. Thus we evaluated the indications, procedural success rate, and in-hospital complications of patients undergoing bare stenting at a single center between 1 October 1995 through 30 September 1996. A total of 363 coronary interventions were performed during this period, including coronary stenting in 194 vessels. In 18 of these 194 vessels, bare-mounted Palmaz-Schatz stents were used. The indications for bare stenting were: inability to deliver the Palmaz-Schatz stent on SDS for suboptimal angioplasty results or acute/threatened abrupt closure; use of half stents; stenting in vessels < 3.0 mm; intermediate disease in the proximal segment that would have precluded optimal visualization of stent placement; and use of guides 7 French or smaller. Bare stenting was successful in 15 of the 18 patients (vessels) in whom it was attempted. There were no deaths, myocardial infarctions, stent thrombosis, repeat interventions, or significant bleeding in patients with successful bare stent delivery. The stents were successfully retrieved in the three patients in whom the stent could not be advanced into the target coronary segment. One of these patients had a propagated spiral dissection prior to attempts at bare stenting and required emergent bypass surgery. The remaining two patients with failed deployment had suboptimal angioplasty results but had an uncomplicated hospital course. Thus bare stenting represents an alternate percutaneous approach to tackle suboptimal procedural results and/or complications in patients who have failed stent deployment with the standard sheathed stent delivery system currently available in the United States.

Angioplasty, Balloon, Coronary↗

Molecular cloning and sequence analysis of the porcine insulin-like growth factor binding protein-5 complementary deoxyribonucleic acid.

We report here for the first time the isolation of a cDNA clone containing the open reading frame sequence for porcine insulin-like growth factor binding protein-5 (pIGFBP-5) and the complete deduced amino acid sequence for this porcine IGFBP. The cDNA sequence shares 94%, 90% and 91% identity to its human, mouse and rat counterparts, respectively. The deduced amino acid sequence consists of 252 amino acids and a putative 19 amino acid signal and shares 97%, 96%, and 96% identity to the human, mouse and rat peptides, respectively. The mature peptide contains the 18 conserved cysteines found in all of the IGFBPs. Northern blot analysis of total RNA isolated from porcine heart, muscle and spleen using a 315 base pair cDNA insert derived from the pIGFBP-5 open reading frame sequence revealed a single mRNA transcript of 6.0 kilobases.

Amino Acid Sequence↗

Reduction of experimental canine myocardial infarct size with prostaglandin E1: inhibition of neutrophil migration and activation.

The ability of prostaglandin E1 (PGE1) to reduce myocardial infarct size in an anesthetized open-chest canine model of regional myocardial ischemia and reperfusion was investigated. Administration of PGE1 (100 ng/kg/min into the left atrium) to dogs beginning 10 min after left circumflex coronary artery (LCCA) occlusion and continuing up to 2 hr of reperfusion resulted in a 43% reduction in infarct size expressed as a percentage of the area at risk: control infarct, 44.3 +/- 3.2%, n = 15; PGE1, 27.3 +/- 3.2%, n = 19, P less than .0005. Regional myocardial blood flow (measured with tracer-labeled microspheres in six dogs from each group) was similar between treatment groups at base line, 5 min after LCCA occlusion, 80 min after LCCA occlusion and 1 hr after LCCA reperfusion. In another group of anesthetized dogs, PGE1 was tested for its ability to decrease neutrophil migration into skin lesions. PGE1 at the same concentration that reduced infarct size, decreased the number of neutrophils (assessed by myeloperoxidase activity) that accumulated in skin lesions after intradermal injection of C5a by 63%. In addition, PGE1 inhibited the production of superoxide anion in vitro by zymosan-stimulated canine neutrophils in a concentration-dependent manner. Thus, PGE1 reduces myocardial infarct size and inhibits neutrophil function in vitro and in vivo. These data suggest that the reduction in infarct size by PGE1 may be due to multiple mechanisms including: 1) inhibition of neutrophil migration and activation at the site of tissue injury or 2) reduction in blood pressure which reduces myocardial oxygen demand.

Alprostadil↗

Iloprost inhibits neutrophil function in vitro and in vivo and limits experimental infarct size in canine heart.

The prostacyclin analogue iloprost (ZK 36374) inhibits neutrophil activation in vitro, reduces neutrophil accumulation in inflammatory skin lesions, and reduces ultimate infarct size in an anesthetized open-chest canine model of regional ischemia and reperfusion. Iloprost (0.1-100 microM) inhibited the in vitro production of superoxide anion by canine neutrophils in a concentration-dependent manner. Iloprost (100 ng/kg/min i.v.) inhibited C5a-induced neutrophil migration into inflammatory skin lesions as assessed by the neutrophil-specific enzyme marker, myeloperoxidase. The myeloperoxidase activity determined 2 hours after the intradermal administration of C5a in each of the groups was control 13.3 +/- 1.8 units/g tissue (n = 12) and iloprost 6.5 +/- 0.9 units/g (n = 12), p less than 0.01. Iloprost was administered to anesthetized open-chest dogs (100 ng/kg/min) 10 minutes after left circumflex coronary artery (LCCA) occlusion and continued during the 90-minute occlusion period and the first 2 hours of reperfusion. Regional myocardial blood flow was similar between treatment groups at baseline, 5 minutes and 80 minutes after LCCA occlusion, and after 1 hour of reperfusion. Infarct size, assessed 6 hours after reperfusion, was reduced by iloprost treatment: 22.4 +/- 3.1% of the area at risk (n = 15) compared with 42.4 +/- 3.3% of control (n = 13), p less than 0.01. Iloprost treatment reduced the accumulation of neutrophils (measured by myeloperoxidase activity) in the ischemic myocardium at the interface between infarcted and noninfarcted tissue: control (n = 9) 9.0 +/- 1.8 units/g tissue, iloprost (n = 6) 2.0 +/- 0.4 units/g, p less than 0.01.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Thermal dilution assessment of proximal aortic and left ventricular mixing chambers in dogs.

The adequacy of left ventricular mixing and the effect of mixing in the left ventricle and aorta on the measurement of the residual fraction by thermal dilution were assessed in open-chest dogs. Temperature was recorded at seven ventricular and two aortic sites during ventricular injections of iced saline at heart rates of 100, 150 and 200 bpm. The residual fraction, K, was calculated for each beat from the inscribed dilution curves and compared with the actual temperature at each measurement site and heart rate. Temperature was non-uniform throughout the ventricle after saline injections indicating incomplete tracer mixing. Thermal equilibration was slowest at the apex and decreased as heart rate increased. K, however, was similar for all sites in the ventricle and aorta at each heart rate by the third beat after saline injection. Thus, in spite of incomplete mixing, the beat-to-beat washout of indicator quickly stabilized which suggests that a reproducible measurement of functional volume can be obtained by this technique.

Animals↗

Electrophysiologic demonstration of concealed conduction in anomalous atrioventricular bypass tracts.

To demonstrate the occurrence of concealed conduction in anomalous atrioventricular (AV) bypass tracts, 11 patients were selected for study. Two had a right-sided and nine had a left-sided bypass tract. Electrode catheters were placed in the right atrium, coronary sinus, AV junction and right ventricle. After every eighth atrial or ventricular driving beat (A1 or V1) at a constant cycle length, two successive atrial or ventricular premature beats (A2 and A3 or V2 and V3) were delivered. The A1A2 or V1V2 interval was fixed at 30 ms greater than the effective refractory period of the atrium or right ventricle, but less than the effective refractory period of the bypass tract in the anterograde or retrograde direction. This allows A2 or V2 to capture the atrium or ventricle, but not conduct in the bypass tract. The A3 or V3 was delivered from late diastole with a progressively shorter A2A3 or V2V3 interval until atrial or ventricular refractoriness was encountered. In the anterograde direction, the presence of A2 prevented A3 conduction in the bypass tract despite A1A3 intervals being longer than the anterograde effective refractory period of the bypass tract in 8 of the 11 patients. In the retrograde direction, the presence of V2 prevented V3 conduction in the bypass tract despite V1V3 intervals being longer than the retrograde effective refractory period of the bypass tract in 3 of the 11 patients. Thus, using the technique of programmed electrical stimulation, concealed conduction in anomalous AV bypass tracts can be demonstrated in both anterograde and retrograde directions.

Adult↗

High-speed eight-channel thermocouple amplifier.

An eight-channel thermocouple amplifier system was constructed to measure rapid changes in temperature of only 1 or 2 degrees C simultaneously from many sites within the heart. The system has a response time of less than 5 ms, a resolution of less than 0.025 degrees C, and a voltage gain of approximately 2,500.

Animals↗