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Biomedical subjects

T J Collins

Publications and source records attributed to T J Collins.

At least 19 recordsLinked to original sources

Morphologic comparison of atherosclerotic lesions in native coronary arteries and saphenous vein graphs with intracoronary angioscopy in patients with unstable angina.

BACKGROUND: Coronary vein grafts develop accelerated atherosclerosis after aortocoronary bypass surgery. Previous pathologic studies have suggested that the morphologic appearance of atherosclerotic lesions in saphenous vein grafts may have subtle differences compared with those of native coronary arteries and may be more prone to disruption and thrombus formation. However, a comparative in vivo assessment of the angioscopic morphology differences between these two types of vessels has not been reported previously. We compared the angioscopic lesion morphology of native coronary arteries and saphenous vein grafts in patients with unstable angina. METHODS AND RESULTS: Percutaneous coronary angioscopy was performed in 60 consecutive patients with unstable angina. Plaque color, texture, friability, and the presence of atherosclerotic plaque ulceration or intracoronary thrombus were noted in the culprit lesion. The culprit lesion was located in native coronary arteries in 42 (70%) patients and in a saphenous vein graft in 18 (30%) patients. There were no significant differences in age, sex, and coronary risk factors including tobacco use, hypertension, hypercholesterolemia, or diabetes mellitus between the two populations. There were also no significant differences between the two groups in terms of plaque color, surface texture, or the incidence of complex plaque morphology (plaque ulceration and intracoronary thrombosis). Loosely adherent, friable plaque, detected by angioscopy, was absent in native coronary arteries and was present in 44% of the saphenous vein grafts (p < 0.0001). CONCLUSIONS: The results of our angioscopic study indicate that other than a high incidence of plaque friability in vein grafts, the surface morphology of culprit lesions in unstable angina patients is quite similar for saphenous vein grafts and native coronary arteries.

Angina, Unstable

Permeability, cytotoxicity, and genotoxicity of chromium (V) and chromium (VI) complexes in V79 Chinese hamster lung cells.

The genotoxicity of Cr(V) complexes in mammalian cells (V79 Chinese hamster lung cells) has been studied for the first time using the in vitro micronucleus assay. Two complexes were investigated, [CrO(ehba)2]-, which undergoes ligand-exchange and disproportionation reactions in the cell growth medium, and [CrO(mampa)]-, which is chemically inert in the medium for the duration of the exposure period. Results of in vitro micronucleus assays show that both complexes are genotoxic and exhibit similar potencies to that of [Cr2O7]2-. The permeabilities of the Cr(V) complexes were also investigated for the first time using particle-induced X-ray emission (PIXE) analysis of individual cells. The Cr uptake increased in the order: [Cr(phen)2-(H2O)2]3+ < [CrO(ehba)2]- < [CrO(mampa)]- < [Cr2O7]2-. Clonal assays showed that Cr(VI) exhibits an expectedly higher cytotoxicity than the Cr(V) complexes. While the genotoxicities of the Cr(V) and Cr(VI) complexes increase according to their permeabilities, the genotoxicities of the Cr(V) complexes are equal to, if not greater than, that of Cr(VI) in terms of the amount of Cr entering the cell. This supports other evidence that Cr(V), produced as a metabolic intermediate from the intracellular reduction of Cr(VI), may be important in Cr-induced cancers.

Animals

Renal artery stent placement: utility in lesions difficult to treat with balloon angioplasty.

OBJECTIVES: We assessed the safety and efficacy of stent placement in patients with poorly controlled hypertension and renal artery stenoses, which are difficult to treat with balloon angioplasty alone. BACKGROUND: Preliminary experience with stent placement suggests improved results over balloon angioplasty alone in patients with atherosclerotic renal artery stenosis. METHODS: Balloon-expandable stents were placed in 100 consecutive patients (133 renal arteries) with hypertension and renal artery stenosis. Sixty-seven of the patients had unilateral renal artery stenosis treated and 33 had bilateral renal artery stenoses treated with stents placed in both renal arteries. RESULTS: Angiographic success, as determined by quantitative angiography, was obtained in 132 (99%) of 133 lesions. Early clinical success was achieved in 76% of the patients. Six months after stent placement, the systolic blood pressure was reduced from 173 +/- 25 to 147 +/- 23 mm Hg (p < 0.001); the diastolic pressure from 88 +/- 17 to 76 +/- 12 mm Hg (p < 0.001); and the mean number of antihypertensive medications per patient from 2.6 +/- 1 to 2.0 +/- 0.9 (p < 0.001). Angiographic follow-up at a mean of 8.7 +/- 5.0 months in 67 patients revealed restenosis (>50% diameter narrowing) in 15 (19%) of 80 stented vessels. CONCLUSIONS: Renal artery stenting is an effective treatment for renovascular hypertension, with a low angiographic restenosis rate. Stent placement appears to be a very attractive therapy in patients with lesions difficult to treat with balloon angioplasty such as renal aorto-ostial lesions and restenotic lesions, as well as after a suboptimal balloon angioplasty result.

Aged

Effects of renal artery stent implantation in patients with renovascular hypertension presenting with unstable angina or congestive heart failure.

This study evaluates the effect of renal artery stent implantation in patients with renovascular hypertension presenting with unstable angina (n = 20) or congestive heart failure (n = 28). There was a significant improvement in the Canadian Cardiovascular Society angina class and the New York Heart Association functional class, and at 8.4 +/- 6.4 month follow-up.

Aged

Allograft aortopathy: an in vivo study of donor aorta involvement in cardiac allograft vasculopathy.

Limited histopathologic studies of failed cardiac allografts have demonstrated that cardiac allograft vasculopathy extends into the donor aorta; however, no study has examined the development of allograft aortic intimal proliferation in vivo in conjunction with coronary intimal hyperplasia. By using simultaneous intracoronary and intraaortic ultrasound, we studied 20 consecutive heart transplant recipients at 2.5 +/- 2.1 years after transplantation. The degree of coronary intimal thickening was strongly correlated with the development of intraaortic intimal hyperplasia (r = 0.90; p < 0.0001). Multivariate predictors of aortic intimal thickening included years after transplant (r = 0.47; p = 0.03), serum cholesterol level (r = 0.65, p = 0.003), and serum triglyceride level (r = 0.51; p = 0.03). Allograft aortopathy occurs in a similar manner to allograft coronary disease, thus providing support for the notion that an immunologic stimulus operating across the allograft vascular bed may be responsible for the development of cardiac allograft vasculopathy. Furthermore, this investigation provides insight into the putative role of hyperlipidemia in allograft vascular disease.

Aorta

Inhibition of nitric oxide facilitates LH release from rat pituitaries.

We examined the effects of nitric oxide (NO) modulators on rat pituitary LH content in vivo and studied their response to LHRH-stimulated LH secretion in vitro in ovariectomized adult female Sprague Dawley rats. Alzet mini pumps (flow rate 10 microl/h) delivering either normal saline (Group I, 1.2 mg nitroglycerin, a donor of NO (Group II) or 50 mg of nitro-L-Arginine methyl ester, a NO synthase (NOS) inhibitor (Group III), were subcutaneously implanted into experimental animals. Following 36 h infusion, pituitaries were removed and either frozen for LH quantitation, or fragmented and challenged in the superfusion system with 10 min pulses of LHRH (1 ng/ml) at 90 min intervals for 10 hours. LH was assayed by radio-immunoassay (RIA) in the homogenates of pituitaries and in aliquots of the superfusate collected every 10 mins. Significantly lower pituitary LH levels were noted in Group III (150.3 +/- 18.6 ng) in comparison to Groups I (215.6 +/- 5.5 ng; p<0.04) or II (221.2 +/- 14.9 ng; p<0.01), suggesting that low levels of NO stimulate LH secretion in vivo. The pituitary LH contents were not significantly different in Groups I and II. In vitro studies reveal that exogenous LHRH stimulated response, measured as average pulse response (90 minute period after LHRH), and total LH released during the 10 hour perfusion, was 290 +/- 23.6 ng and 1646.7 +/- 270.8 ng, respectively, in Group III; 57.9 +/- 3.1, and 344.7 +/- 24.3 ng in Group I, and 105.3 +/- 6.3, and 633.7 +/- 77.1 mg in Group II. Thus, our in vitro studies demonstrate significantly enhanced (p<0.05) LHRH- stimulated LH secretion in Group III in comparison to Groups I and II, while Group II shows higher responsiveness than Group I (p<0.05). The results of the current studies provide evidence that NOS inhibition facilitates pituitary LH secretion. The differential responses to LHRH-stimulated LH secretion in vitro in the 3 groups suggest a possible role of NO in modulating pituitary LHRH receptor concentrations. However, this will have to be tested by further studies.

Animals

Peptide biotinylation with amine-reactive esters: differential side chain reactivity.

N-hydroxysuccinimide (NHS) esters of biotin are reported to react specifically with amino groups of peptides and proteins. However, we have found that these reagents can readily acylate other functional groups in specific peptide sequences under relatively mild conditions. We have extended our inquiry of sequence-dependent acylation by evaluating the reactivity of a variety of commonly employed biotinylation reagents typically used for amino group modification. These included the p-nitrophenyl ester of biotin, NHS-esters of biotin containing aminohexanoic acid spacer arms, and a sulfonated NHS-biotin ester that contained a disulfide bond within its spacer. The decapeptide [D-Lys6]gonadotropin releasing hormone was employed as a model peptide. Reaction products were characterized by high-performance liquid chromatography, amino acid compositional analysis, reaction with hydroxylamine, and mass spectrometry. In addition to the O-acylation of Ser4 and Tyr5 in this peptide, we have also identified a novel biotinylation of the Arg8 side chain.

Acylation

Heterogeneity of cardiac allograft vasculopathy: clinical insights from coronary angioscopy.

OBJECTIVES: With this study, we sought to examine the heterogeneity of cardiac allograft vasculopathy in vivo using coronary angioscopy as an adjunct to intravascular ultrasound, and we evaluated the clinical relations of immunologic and nonimmunologic risk factors with the different forms of cardiac allograft vasculopathy detected angioscopically. BACKGROUND: Intravascular ultrasound detects vascular intimal proliferation accurately but is limited in its ability to delineate morphologic characteristics. Coronary angioscopy can evaluate intimal surface morphology by direct visualization and can differentiate pathologically distinct forms of plaque topography on the basis of color and contour. METHODS: We studied 107 consecutive heart transplant recipients with intravascular ultrasound and angioscopy at the time of their annual angiogram, and we assessed the relation of nonimmunologic and immunologic risk factors to the development of cardiac allograft vasculopathy distinguished angioscopically into a pigmented (yellow) or nonpigmented (white) intimal thickening. We further evaluated the clinical differences in cardiac events among these two forms of angioscopically heterogeneous forms of cardiac allograft vasculopathy. RESULTS: Significant clinical predictors of nonpigmented intimal thickening were advanced donor age and lower mean cyclosporine levels, whereas hyperlipidemia, cumulative prednisone dose and time since transplantation correlated with pigmented intimal hyperplasia. In addition, comparisons between the two angioscopic groups revealed increased intimal thickening, serum cholesterol, low density lipoprotein cholesterol, acute allograft rejection and time since transplantation in the group with pigmented intimal thickening (p < 0.05). With regard to cardiac events, nonpigmented plaque was more frequently found in the sudden death group (53% vs. 20%, p = 0.05), whereas the nonsudden cardiac event group had a significantly higher prevalence of pigmented plaque (80% vs. 47%, p = 0.07). CONCLUSIONS: These findings indicate that cardiac allograft vasculopathy is a heterogeneous disease with varied morphologic expressions with different clinical implications. Furthermore, this investigation provides insight into the cohesive, yet diverse influences of various factors, particularly immunosuppression, in these forms of cardiac allograft vasculopathy.

Adult

Microprobe X-ray absorption spectroscopic determination of the oxidation state of intracellular chromium following exposure of V79 Chinese hamster lung cells to genotoxic chromium complexes.

The oxidation state of intracellular chromium has been determined directly in mammalian lung cells exposed to mutagenic and carcinogenic chromium compounds. Microprobe X-ray absorption spectroscopy (XAS) experiments on single V79 Chinese hamster lung cells showed that Cr(VI) and Cr(V) complexes were reduced completely (>90%) to Cr(III) within 4 h of exposure of the cells. This result provides direct evidence for the hypothesis that these genotoxic oxidants react rapidly with intracellular reductants.

Animals

Minimally invasive direct coronary artery bypass surgery.

Three patients with isolated disease of the left anterior descending coronary received a minimally invasive direct coronary artery bypass operation. All were discharged from the hospital in 2 days and are doing well. This is an exciting new procedure which combines the long-term benefits of bypass using the mammary artery with a shortened hospital stay and a rapid postoperative recovery.

Coronary Artery Bypass

Coronary thrombi increase PTCA risk. Angioscopy as a clinical tool.

BACKGROUND: The presence of angiographically identified intracoronary thrombus has been variably associated with complications after coronary angioplasty. Angiography has been shown to be less sensitive than angioscopy for detecting subtle details of intracoronary morphology, such as intracoronary thrombi. The clinical importance of thrombi detectable by angioscopy but not by angiography is not known. METHODS AND RESULTS: Percutaneous coronary angioscopy was performed in 122 patients undergoing conventional coronary balloon angioplasty (PTCA) at six medical centers. Unstable angina was present in 95 patients (78%) and stable angina in 27 (22%). Therapy was not guided by angioscopic findings, and no patient received thrombolytic therapy as an adjunct to angioplasty. Coronary thrombi were identified in 74 target lesions (61%) by angioscopy versus only 24 (20%) by angiography. A major in-hospital complication (death, myocardial infarction, or emergency bypass surgery) occurred in 10 of 74 patients (14%) with angioscopic intracoronary thrombus, compared with only 1 of 48 patients (2%) without thrombi (P = .03). In-hospital recurrent ischemia (recurrent angina, repeat PTCA, or abrupt occlusion) occurred in 19 of 74 patients (26%) with angioscopic intracoronary thrombi versus only 5 of 48 (10%) without thrombi (P = .03). Relative risk analysis demonstrated that angioscopic thrombus was strongly associated with adverse outcomes (either a major complication or a recurrent ischemic event) after PTCA (relative risk, 3.11; 95% CI, 1.28 to 7.60; P = .01) and that angiographic thrombi were not associated with these complications (relative risk, 0.85; 95% CI, 0.36 to 2.00; P = .91). CONCLUSIONS: The presence of intracoronary thrombus associated with coronary stenoses is significantly underestimated by angiography. Angioscopic intracoronary thrombi, the majority of which were not detected by angiography, are associated with an increased incidence of adverse outcomes after coronary angioplasty.

Adult

Endovascular stenting for treatment of an adult patient with pulmonary artery stenosis with 1-year follow-up.

This report describes the occurrence of symptomatic proximal left main pulmonary artery stenosis in a 58-yr-old man that was successfully treated with endovascular stenting with 1-yr follow-up. The technique and pitfalls of this procedure are described. Endovascular stenting provided a well-tolerated, nonsurgical approach to alleviating isolated pulmonary artery stenosis in this patient.

Angiography

Myocardial contrast echocardiography in human beings: correlation of resting perfusion defects to sestamibi single photon emission computed tomography.

The presence of myocardial perfusion abnormalities is generally accepted to suggest underlying coronary artery disease. In previous animal studies, myocardial contrast echocardiography (MCE) has been shown to be useful in delineating areas at risk after coronary occlusions. We sought to compare the presence or absence, size, and location of perfusion defects detected in human beings by MCE and sestamibi single photon emission computed tomography (SPECT). Regional wall motion was qualitatively assessed in the parasternal and apical views of a resting two-dimensional echocardiogram. Coronary angiography was performed in all patients and myocardial contrast echocardiography performed with 2 ml of intracoronary sonicated meglumine (Nycomed). A cine loop of the digitized contrast echocardiograms was used to analyze perfusion defects. Gated SPECT resting images in standard views were obtained after technetium 99m sestamibi (20 mCi) was administered. Visually perceived perfusion defects were established at 30% of maximal counts at end diastole. Perfusion defects by both techniques were planimetered, assigned to one of three perfusion artery territories, and expressed as a percentage of the perfusion territory studied. Comparison was made by linear regression analysis. Forty-one patients were studied. Perfusion defects were observed in 12 (29%) patients by MCE, 19 (46%) patients by SPECT, and 11 (27%) patients by both techniques. No perfusion defects were detected by MCE in 29 (70%) patients, by SPECT in 22 (53%) patients, or by either technique in 21 (51%) patients. The two techniques agreed in 78% of the patients. In 67 matching orthogonal views suitable for comparison between the two techniques, an 82% concordance for the presence or absence of defects was observed. The location of the defects matched in 86% of the cases. A significant correlation (p < 0.001; r = 0.62) between these techniques was observed in assessing the size of perfusion defects. In conclusion, our results suggest that MCE and sestamibi SPECT are comparable techniques for detecting severely underperfused myocardium in human beings.

Adult

Predictive model to assess risk for cardiac allograft vasculopathy: an intravascular ultrasound study.

OBJECTIVES: This study was performed to assess the influence and interdependence of immunologic and nonimmunologic risk factors in the development of cardiac allograft vasculopathy. Another primary objective was to establish a clinically useful model for risk assessment of cardiac allograft vasculopathy that would facilitate identifying those heart transplant recipients likely to have severe intimal proliferation and thereby at greater risk for adverse clinical events. BACKGROUND: To our knowledge, no comprehensive intravascular ultrasound study has assessed the relative influences of both nonimmunologic and immunologic factors in the development of cardiac allograft vasculopathy, currently the major limitation to long-term cardiac allograft survival. METHODS: Using a computer-assisted model of stepwise logistic regression, immunologic and nonimmunologic risk factors were evaluated to help identify the development of severe intimal thickening in 101 subjects who underwent intravascular ultrasound. Prospective validation of the findings was performed in a separate consecutive cohort of 37 heart transplant recipients, and the accuracy of this model to predict a relative risk > 1 for the development of severe intimal hyperplasia was assessed. RESULTS: Significant independent predictors of severe intimal hyperplasia in this model included a donor age > 35 years, a first-year mean biopsy score > 1 (a measure not only of severity of rejection, but also of frequency of insidious rejection) and hypertriglyceridemia at two incremental levels of risk (150 to 250 mg/dl [1.70 to 2.83 mmol/liter] and > 250 mg/dl [2.83 mmol/liter]). Based on the absence (0) or presence (1) of these factors, 12 individual categories of risk were ascertained with increasing relative risks and predicted probabilities for severe intimal hyperplasia. Prospective validation of this model revealed a sensitivity and specificity of 70% and 90%, respectively, and the positive and negative predictive values were 85% and 80%, respectively. Additionally, subjects with severe intimal thickening had a four-fold higher cardiac event rate than those without severe intimal proliferation on intravascular ultrasound. CONCLUSIONS: This study establishes a clinically useful predictive model that can be applied to individual heart transplant recipients to assess their risk for developing significant cardiac allograft vasculopathy and, thus, aids in the identification of patients at risk for cardiac events in whom closer surveillance and risk factor modification may be warranted.

Adult

Unstable angina. A comparison of angioscopic findings between diabetic and nondiabetic patients.

BACKGROUND: Patients with diabetes mellitus have a higher prevalence of atherosclerotic heart disease and a higher incidence of myocardial infarction than the general population. Diabetic patients also have several hematologic, rheologic, and metabolic abnormalities not present in their nondiabetic counterparts that may predispose them to atherosclerotic plaque rupture and intraluminal thrombosis and consequently may lead to the formation of morphologically complex plaques and the development of acute coronary syndromes. METHODS AND RESULTS: Percutaneous coronary angioscopy was performed in 55 consecutive patients with unstable angina. We observed plaque color, texture, and the incidence of intracoronary thrombus associated with the culprit lesions of these patients. The population consisted of 17 (31%) diabetic and 38 (69%) nondiabetic patients. The presence of coronary risk factors was not significantly different between the two populations. Ulcerated plaque was found in 16 of 17 (94%) diabetic patients versus 23 of 38 (60%) nondiabetic patients (P = .01). Intracoronary thrombi were seen in 16 of 17 (94%) diabetic patients versus 21 of 38 (55%) nondiabetic patients (P = .004). CONCLUSIONS: The results of the angioscopic examination show that diabetic patients with unstable angina have a higher incidence of plaque ulceration and intracoronary thrombus formation than nondiabetic patients. This increased frequency of complex lesion morphology is consistent with the disproportionately higher risk for development of acute coronary syndromes in these patients.

Aged