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Biomedical subjects

S T Crowley

Publications and source records attributed to S T Crowley.

13 recordsLinked to original sources

Prevalence of persistent asymptomatic proteinuria in HIV-infected outpatients and lack of correlation with viral load.

AIM: Human immunodeficiency virus-associated nephropathy (HIVAN) is projected to be a leading cause of end-stage renal disease (ESRD) in young African American men in the new millennium. Little is known about the early natural history of the disease, including the prevalence of asymptomatic nephropathy. The primary aim of this study was to define the prevalence of persistent asymptomatic proteinuria in a contemporary, ambulatory human immunodeficiency virus- (HIV) infected population. The secondary aim was to correlate the presence of persistent proteinuria with measures of HIV disease. METHODS: Using a readily available screening tool, the urine dipstick, we determined the prevalence of persistent asymptomatic proteinuria in the outpatient VA Connecticut (VA CT) Healthcare System West Haven HIV Clinic population. We compared the presence of persistent proteinuria with measures of HIV viral disease. RESULTS: The prevalence of persistent asymptomatic proteinuria was 14% (7 of 49 patients). The presence of persistent proteinuria was not correlated with viral load. CONCLUSIONS: A significant prevalence of occult renal disease exists in the asymptomatic HIV-seropositive outpatient population and is not correlated with viral load.

AIDS-Associated Nephropathy↗

Reproducibility of ambulatory blood pressure monitoring in hemodialysis patients.

Ambulatory blood pressure monitoring (ABPM) has been increasingly used in hemodialysis (HD) practice and research; however, no study has evaluated the reproducibility of ABPM in this population. To address this question, we performed 48-hour interdialytic ABPM on 21 HD patients (mean age, 53 +/- 16 years; 7 women) on two different occasions 68 +/- 34 days (range, 30 to 154 days) apart. To qualify for the protocol, patients had to be at the same dry weight and on the same vasoactive drug regimen at both monitoring periods. BP was analyzed according to three different methods: isolated pre-HD and post-HD values, average pre-HD and post-HD values for the five HD sessions surrounding each monitoring period, and 48-hour interdialytic ABPM. Reproducibility was determined by analysis of the SD of the differences (SDD) between the two monitoring periods and the coefficient of variation of each method of BP determination. Our results show better reproducibility of ABPM (SDD, 10.6/6.6 mm Hg; coefficient of variation, 7.5%/8.1%) compared with isolated pre-HD BP (SDD, 24.4/11.3 mm Hg; coefficient of variation, 16.7%/14.1%) or post-HD BP (SDD, 16.8/14.5 mm Hg; coefficient of variation, 11.7%/17.8%), and averaged pre-HD BP (SDD, 14.7/7.2 mm Hg; coefficient of variation, 10.1%/9.1%) or post-HD BP (SDD, 12.4/8.7 mm Hg; coefficient of variation, 8.9%/11.1%). The reproducibility of the decrease in BP during sleep was poor, with up to 43% of the subjects changing dipping category within or between interdialytic periods. We conclude that ABPM is the most accurate method to study BP in HD patients over time. However, variability is significant, and there is poor reproducibility of the nocturnal decline in BP.

Blood Pressure↗

Delayed gallium-67 uptake in renal atheroembolic disease.

The differentiation between atheroembolic disease (AED) and allergic interstitial nephritis (AIN) may pose a clinical challenge. Gallium scans have been proposed to identify AIN with good discriminating ability. We report herein a case of atheroembolic disease presenting as acute renal failure with persistent delayed uptake of gallium-67 by nuclear imaging. The distinction between AED and AIN could be made only with a renal biopsy, which confirmed the correct diagnosis. This case report and the presented review of the literature suggest that gallium scans are nonspecific and should not supplant renal biopsy for definitive histological diagnosis.

Acute Kidney Injury↗

Validation of the SpaceLabs 90207 ambulatory blood pressure device for hemodialysis patients.

BACKGROUND: Background Ambulatory blood pressure monitoring (ABPM) has been used increasingly in assessing dialysis patients. However, devices have not been validated formally for this population. Formal device validation is important in order to guarantee adequate performance for populations with special characteristics, such as patients undergoing hemodialysis. OBJECTIVE: To achieve formal validation of the SpaceLabs 90207 ambulatory blood pressure device (SLD) using a modified British Hypertension Society protocol. METHODS: Eighty-five hemodialysis patients were studied, generating 255 readings. Readings were obtained with patients supine (in a dialysis chair) over 5-10 min during hemodialysis. Simultaneous, same-arm readings were obtained through the use of a T connector to a calibrated mercury manometer. The mean differences between readings obtained by observers and those obtained by the device were calculated. Limits of agreement between observers and SLD were determined and plotted according to the method of Bland and Altman. For grading of performance, we determined the number of readings for which the readings obtained by the device were within 5, 10, and 15mmHg of manometer readings. Final gradings were ascribed according to British Hypertension Society criteria. RESULTS: The mean blood pressure (+/-SD) was 141/76+/-31/15mmHg (observers) and 141/77+/-27/15mmHg (SLD), and the mean (+/-SD) difference between observers and device (observer-device) was -0.5+/-7.5mmHg for systolic blood pressure (SBP) and -0.2+/-5.2mmHg for diastolic blood pressure (DBP). The device was less accurate in extreme ranges of SBP. In fact, there was a positive correlation between average [(observer+device)/2] and difference (observer-device) for SBP (r =0. 54, P <0.0001), showing that underestimation in higher ranges, and overestimation in lower ranges of blood pressure occurred for SBP. For SBP, 53% of readings were within 5mmHg of those obtained by the observers, 85% were within 10mmHg, and 97% within 15mmHg. For DBP, 78% were within 5mmHg, 96% within 10mmHg, and 98% within 15mmHg. These observations conferred on the device grade C for SBP and grade B for DBP. The type of vascular access and the presence of non-functioning arteriovenous grafts and fistulas in the ipsilateral arm did not alter these results significantly. CONCLUSIONS: These data validate the use of this device for hemodialysis patients. However, caution should be exercised in the evaluation of upper and lower ranges of SBP.

Adult↗

Percutaneous transluminal angioplasty of internal mammary arteries in patients with rest angina.

Angioplasty of the internal mammary artery (IMA) bypass graft has been shown to be a safe and effective revascularization procedure. However, angiographic and long term clinical outcomes in the high-risk group of patients presenting with rest angina has not been well documented. We report the results of IMA angioplasty in 20 patients with rest angina out of 614 (3.2%) who received a left IMA graft at our institution between April 1987 and September 1994. All patients were admitted with rest angina, 12 patients demonstrated persistent ischemia despite medical therapy, two patients were in heart failure, and one patient was in cardiogenic shock. Balloon angioplasty was successful in 15 of 20 patients (75%). Failed angioplasty was associated with either severe IMA tortuousity (three patients) or inability to cross the anastomotic stenosis with the guide wire (two patients). Each of these five patients required angioplasty of either the native left anterior descending artery or other saphenous vein grafts for clinical stabilization. No patient suffered a major complication (myocardial infarction, emergent coronary bypass surgery, death). Clinical follow-up was obtained in all 20 patients (6 months, 7 years, mean 27 months). Twelve patients (60%) were asymptomatic or had stable angina at follow-up, and 8 returned with anginal symptoms. Four patients required repeat angioplasty for disease in other vessels, two were treated medically for angina, one underwent repeat CABG, and cardiac transplantation was performed in one patient for refractory heart failure. Angiographic follow up was obtained in 10/15 (66%) successful angioplasty patients, and only one patient demonstrated restenosis at the treated site (10%). During follow up one patient developed an IMA stenosis at a previous dissection site in the body of the graft that was treated with angioplasty. These results suggest that IMA angioplasty in patients with rest angina is associated with excellent long term patency and clinical efficacy, as well as low procedural risk.

Adult↗

Systolic blood pressure response to percutaneous transluminal coronary angioplasty for cardiogenic shock.

This study reports that an improvement in systolic blood pressure of > 10 mm Hg after PTCA in patients with cardiogenic shock was associated with in-hospital survival (8 of 8 patients). Failure to achieve infarct artery patency (6 of 6) or technically successful PTCA, unaccompanied by improved systolic blood pressure in the catheterization laboratory, was associated with in-hospital mortality in this series.

Aged↗

Multiple growth factors are released from mechanically injured vascular smooth muscle cells.

Local release of mitogenic and chemotactic signals during angioplasty-induced vascular injury may initiate restenosis. We investigated whether mechanical injury to vascular smooth muscle cells (VSMC) results in the release of biologically active peptide growth factors. Monolayers of bovine SMC cultures were mechanically injured by cell scraping. Conditioned medium (CM) from control and injured SMC cultures was collected, and the mitogenic activity was measured by [3H]thymidine incorporation in recipient SMC cultures. Mitogenic activity from injured CM was detected within 15 min after injury. When the CM from injured cells was removed 15 min after injury and replaced with serum-free media, there was no detectable mitogenic activity in the replacement CM assessed 1-6 days postinjury. Suramin, a nonspecific peptide growth factor antagonist, significantly inhibited the mitogenic activity of injured CM. Basic fibroblast growth factor (bFGF), platelet-derived growth factor (PDGF A chain), and epidermal growth factor (EGF) were detected in CM from injured cells by immunoblot analysis. The mitogenic activity of injured CM was significantly inhibited with neutralizing antibodies to bFGF (34%), PDGF-AA (32%), PDGF-BB (25%), and EGF (25%). A neutralizing antibody to transforming growth factor (TGF)-beta had no effect. In conclusion, bFGF, PDGF, and EGF are immediately released from mechanically injured VSMC. VSMC likely contain preformed, biologically active growth factors that are efficiently released from the cell cytoplasm following mechanical injury. Conditioned medium from injured VSMC is highly mitogenic, and this activity is probably due to multiple growth factors interacting synergistically.

Animals↗

Renal hemodynamic response to the creation of vascular access in patients with end-stage renal disease.

To evaluate the possibility that the placement of arteriovenous anastomosis (a/v a) may lead to the attenuation of glomerular hyperfiltration, we studied 5 nondiabetic patients before and after creation of vascular access for hemodialysis. Patients received no EPO and antihypertensive therapy was discontinued 24 h before each study. Cardiac output (CO) and a/v a flow rates were measured by Doppler echo, and GFR and ERPF by plasma decay curves of Tc99m DTPA and 131I-hippuran, respectively. Other parameters were calculated by standard formulas. Augmentation of CO and decrease in systemic vascular resistance occurred in all patients (p = 0.05), yet renal findings were less predictable since only three patients showed a decrease in renal vascular resistance and filtration fraction post a/v a. Thus, there is a discordant pattern of renal hemodynamic response to the creation of a/v a in end-stage renal disease and further studies are needed to better define the subset of patients who are prone to renal vasodilation after the placement of a/v a.

Adult↗

Percutaneous transluminal coronary angioplasty of the left main coronary artery in patients with rest angina.

Left main coronary angioplasty may be a therapeutic revascularization procedure for a subset of patients with symptomatic coronary artery disease. The purpose of this study is to report procedural outcomes and long-term clinical follow-up of 15 patients who underwent either protected or unprotected left main angioplasty for rest angina. These patients represent a cohort of unstable angina patients who were considered high risk for coronary artery bypass surgery. Ten of 15 patients had Canadian Heart Class IV angina, and three patients were hemodynamically unstable. Balloon angioplasty was successful in 4 patients, and one patient was treated with directional atherectomy. Initial angiographic success was achieved in 14 of 15 patients (93%). Major complications (myocardial infarction, emergent coronary artery bypass graft, death) occurred in one patient (6%); 73% of the patients were asymptomatic or had stable exertional angina at 6 months follow-up. One year survival was 87% (13 of 15). During the follow-up period six patients had repeat catheterization for recurrent angina. Four of these patients had left main restenosis and underwent successful repeat left main angioplasty. No patient had coronary bypass surgery during follow-up. This report suggests that left main angioplasty can be a safe and effective revascularization procedure for critically ill patients with unstable angina who are at high risk for coronary bypass surgery.

Aged↗

Percutaneous transluminal angioplasty of saphenous vein grafts for medically refractory unstable angina.

OBJECTIVES: We attempted to answer the question, Is balloon angioplasty a reasonable alternative to repeat coronary artery bypass graft surgery in patients with previous coronary bypass graft surgery, medically refractory unstable angina and vein graft lesions? BACKGROUND: Patients with medically refractory unstable angina need revascularization. Patients with previous coronary artery bypass graft surgery and medically refractory angina are at "high risk" for adverse outcomes with repeat coronary bypass graft surgery. Conversely, patients with angioplasty of old vein grafts are also at "high risk" for adverse outcomes. METHODS: Balloon angioplasty of 89 lesions in saphenous vein grafts was performed in 75 consecutive patients with medically refractory unstable angina. Of these 75 patients, 24 (32%) had myocardial infarct within 30 days, 23 (31%) had left ventricular ejection fraction < 0.35, and 50 (67%) had major comorbidity. Patients underwent standard balloon angioplasty with aggressive use of intravenous and intracoronary heparin, urokinase, nitroglycerin, oral aspirin, calcium channel blocking agents and coumadin. RESULTS: Angiographic success (reduction of stenosis < or = 50% without major complication) was seen in 84 of 89 lesions. Clinical success (angiographic success plus hospital discharge without major complication) was seen in 70 of 75 patients. During index hospitalization, two patients (3%) died, two (3%) had nonfatal infarcts, and one (1%) had emergency reoperation (coronary bypass graft surgery). In late follow up (3 to 66 months), 14 (20%) patients were lost to follow-up, 17 (23%) had repeat percutaneous transluminal coronary angioplasty, 2 (3%) had late bypass graft reoperation, 18 (25%) had late death, and 1 (< 1%) had a heart transplant. Of the 41 patients alive after one or more angioplasties, 25 have little or no angina, and 16 have occasional or more angina. We compared long-term survival rate in these 75 patients with a cohort of patients with high risk, unstable angina from the Veterans Affairs Surgical Registry (2,570 patients). The 30-day survival rate was better in patients with coronary angioplasty (97% vs. 92%, p < 0.05), but by 6 months there was no difference, and by 5 years a trend toward a higher survival rate with coronary artery bypass graft surgery was seen. CONCLUSIONS: Balloon angioplasty of saphenous vein grafts with aggressive adjunctive pharmacotherapy is a reasonable alternative to repeat coronary bypass graft surgery in patients with medically refractory unstable angina, previous coronary bypass graft surgery and saphenous vein narrowing.

Aged↗

Platelet-induced vascular smooth muscle cell proliferation is modulated by the growth amplification factors serotonin and adenosine diphosphate.

BACKGROUND: Platelet-mediated mechanisms have been implicated in intimal lesion formation following vascular injury. Although the participation of peptide growth factors has been suspected in this process, little has been known about the possible mitogenic role of other platelet factors that are released at sites of vascular injury. METHODS AND RESULTS: We tested the hypothesis that platelet products, which are not peptide growth factors, are important modulators of the platelet-induced smooth muscle cell (SMC) proliferative response by acting as growth amplification factors. In these studies, cell proliferation was assessed by [3H]thymidine incorporation, flow cytometry, and direct cell counting. We examined the potential mitogenicity of several platelet products, including serotonin, ADP, norepinephrine, histamine, platelet-activating factor, the thromboxane A2 mimetic U46619, and bradykinin. Of the platelet products tested, serotonin and ADP induced a synergistic response with peptide growth factors. This synergy was greatest at low growth-factor concentrations. Addition of nonaggregated platelets to quiescent SMC cultures strongly stimulated cell proliferation. Since the addition of suramin to platelet-treated cultures markedly inhibited SMC proliferation, peptide growth factors are most likely the primary mitogens mediating this response. However, platelet-induced proliferation was also markedly reduced by the serotonin antagonists ketanserin and LY53857 (44%), and by the ADP antagonist apyrase (35%). CONCLUSIONS: Therefore, serotonin and ADP contribute significantly, in synergy with peptide growth factors, to the platelet-induced SMC proliferative response. We propose that in vivo serotonin and ADP act as amplification factors for SMC proliferation at sites of vascular injury.

Adenosine Diphosphate↗

Effects of nonenzymatic glycosylation of mesangial matrix on proliferation of mesangial cells.

Cross-linking of cell matrix components by nonenzymatic glycosylation may contribute to diabetic glomerulopathy. We examined the effects of modification of matrix by nonenzymatic glycosylation on mesangial cell function. Matrix was generated by growing mesangial cells in tissue culture for 2 wk and removing the cells with a detergent cell-lysis solution. By indirect immunofluorescence and Northern-blot analysis, the remaining matrix contained laminin, fibronectin, and collagens type I and IV. The matrix was modified by incubation for 24 h with 50 mM glycolaldehyde, a highly reactive cross-linking nonenzymatic glycosylation product, or for 2 wk with 200 mM glucose-6-phosphate (G6P). Modification was carried out with or without equimolar aminoguanidine, an inhibitor of cross-link formation. Nonenzymatic glycosylation of the matrix by glycolaldehyde or G6P was confirmed by fluorometry and [14C]G6P incorporation and was prevented by aminoguanidine. [3H]thymidine incorporation for 24 h by mesangial cells plated onto unmodified or modified matrix was then performed. Modification of matrix had no effect on attachment of mesangial cells, determined 4 h after plating. Nonenzymatic glycosylation of matrix by glycolaldehyde or G6P significantly inhibited thymidine incorporation by mesangial cells. This effect was partially reversible by aminoguanidine. Aminoguanidine-modified matrix had no effect on thymidine incorporation. Thymidine-incorporation results were confirmed by direct cell counting. We conclude that modification of matrix by nonenzymatic glycosylation influences growth of mesangial cells, which could contribute to the mesangial abnormalities of diabetic glomerulopathy.

Animals↗

Atrial natriuretic factor production during upright exercise.

In an attempt to determine factors that are related to atrial natriuretic factor (ANF) release in normal subjects, 10 male volunteers were studied at rest supine, sitting and during treadmill exercise. Echocardiography was used to measure atrial volumes, and a Swan-Ganz catheter was used to measure right atrial pressure and pulmonary artery wedge pressure. Right ventricular ANF increased from 33 +/- 22 pg/ml supine to 72 +/- 32 pg/ml at peak exercise (p less than 0.001). When heart rate, atrial volume and atrial phasic pressure were combined to calculate atrial minute circumferential wall stress, a significant relationship between left and right atrial values for this variable and ANF was present. An association between norepinephrine (NE) and ANF was also present, but in a multivariate analysis it was not significant. This probably does not represent cause and effect but rather an association due to the relationship between NE and heart rate.

Adult↗