Oxytetracycline Dynamics on Peach Leaves in Relation to Temperature, Sunlight, and Simulated Rain.

Oxytetracycline (OTC), a member of the tetracycline antibiotics, is used as a foliar spray to control Xanthomonas arboricola pv. pruni on stone fruits and Erwinia amylovora on pome fruits. We studied the dynamics of OTC residues on attached peach (Prunus persica) leaves treated with 300 ppm active ingredient of an agricultural OTC in relation to temperature, natural sunlight, and simulated rain. We further evaluated the potential of three ultraviolet (UV) protectants (lignin, titanium dioxide, and oxybenzone) and one sticker-extender (Nu Film-17) to prolong OTC longevity on the leaf surface. OTC residue was determined by high-pressure liquid chromatography (HPLC)-UV (C18 reversed-phase column). In controlled conditions in darkness, constant temperatures up to 40°C did not affect OTC degradation on leaves. In contrast, OTC residue decreased rapidly in natural sunlight in the absence of rain, declining, on average, by 43.8, 77.8, and 92.1% within 1, 2, and 4 days after application, respectively; 7 days after application, OTC levels were near the detection limit. Use of shade fabric with 10 and 40% sunlight transmittance, simulating overcast sky, reduced OTC degradation significantly but did not extend OTC persistence beyond 7 days. Areas under the OTC residue curve, summarizing OTC dynamics during the 7-day exposure period, were negatively and significantly correlated with solar radiation and UV radiation variables, but not with temperature. UV protectants and Nu Film-17 were ineffective in improving OTC persistence in outdoor conditions. Simulated rain at 44 mm h-1 drastically (by 67.2%) lowered OTC residue after 2 min, and levels were near the detection limit after 60 min of continuous rain, regardless of whether plants were exposed to rainfall 1 or 24 h after OTC application. In artificial inoculation experiments with X. arboricola pv. pruni on attached peach leaves, OTC concentrations ≥50 ppm active ingredient (corresponding to ≥0.06 µg OTC cm-2 leaf surface) were sufficient to suppress bacterial spot development. By extrapolation from our outdoor exposure experiments, similar OTC residues following application of labeled OTC rates would be reached after less than 2 days under full sunlight, after 4 days under overcast sky, or after 2 min of a heavy rainstorm.

Expanded nonhuman primate tregs exhibit a unique gene expression signature and potently downregulate alloimmune responses.

We have established two complementary strategies for purifying naturally occurring regulatory T cells (Tregs) from rhesus macaques in quantities that would be sufficient for use as an in vivo cellular therapeutic. The first strategy identified Tregs based on their being CD4+/CD25(bright). The second incorporated CD127, and purified Tregs based on their expression of CD4 and CD25 and their low expression of CD127. Using these purification strategies, we were able to purify as many as 1x10(6) Tregs from 120 cc of peripheral blood. Cultures of these cells with anti-CD3, anti-CD28 and IL-2 over 21 days yielded as much as a 450-fold expansion, ultimately producing as many as 4.7x10(8) Tregs. Expanded Treg cultures potently inhibited alloimmune proliferation as measured by a carboxyfluorescein succinimidyl ester- mixed lymphocyte reaction (CFSE-MLR) assay even at a 1:100 ratio with responder T cells. Furthermore, both responder-specific and third-party Tregs downregulated alloproliferation similarly. Both freshly isolated and cultured Tregs had gene expression signatures distinguishable from concurrently isolated bulk CD4+ T-cell populations, as measured by singleplex reverse transcriptase-polymerase chain reaction (RT-PCR) and gene array. Moreover, an overlapping yet distinct gene expression signature seen in freshly isolated compared to expanded Tregs identifies a subset of Treg genes likely to be functionally significant.

Non-myeloablative conditioning for second hematopoietic cell transplantation for graft failure in patients with non-malignant disorders: a prospective study and review of the literature.

Allogeneic hematopoietic cell transplantation (HCT) effectively treats several non-malignant disorders such as selected lysosomal disorders, cerebral adrenoleukodystrophy and hemoglobinopathies. However, rates of graft failure (GF) in non-malignant populations exceed those of patients with malignant indications for HCT. Salvage conditioning regimens and outcomes for second HCT for GF vary immensely in the literature. We report 17 consecutive pediatric patients with non-malignant disorders who underwent a second allogenic HCT for GF using a non-myeloablative, low-dose busulfan-based regimen. Graft sources for the second transplant included umbilical cord blood, unrelated bone marrow and unrelated PBSCs. Median age at time of second HCT was 6.6 years (1.1-14.6 years). Fourteen of seventeen patients (82%) achieved engraftment, with a 3-year overall survival of 82% (95% CI, 54-94%). Day 100 transplant-related mortality was 12% (95% CI, 0-27%). CMV and adenovirus reactivation occurred in 30% and fungal infections in 18%. The incidence of grade II-IV acute GvHD disease was 35% (95% CI, 13-58%) with only 6% grade III-IV (95% CI, 0-17%). In summary, we illustrate excellent overall survival and acceptable toxicity using a non-myeloablative conditioning regimen for second HCT as salvage therapy for first GF in patients with non-malignant conditions.

Changes in the incidence, patterns and outcomes of graft failure following hematopoietic stem cell transplantation for Hurler syndrome.

Hematopoietic stem cell transplantation (HSCT) is the standard of care in children with Hurler syndrome (HS) as it is the only therapy that can arrest disease progression. We examined the incidence, patterns and outcomes of graft failure in all HS children undergoing first HSCT at the Royal Manchester Children's Hospital or the University of Minnesota Children's Hospital from 1983 to 2016. Implementation of busulfan pharmacokinetic monitoring started in 2004 in both institutions. Two hundred and forty HS children were included in this analysis (historical era (pre-2004), n=131; current era (post 2004), n=109). The proportion of patients with graft failure was significantly lower in the current era compared with the historical era (37.2% vs 10.1%, respectively). Of 49 patients with graft failure in the historical era, 1 had aplasia and 48 had autologous reconstitution. All the 11 graft failures of the current era occurred in recipients of cord blood transplants (7 aplasia and 4 autologous reconstitution). The outcomes of second transplant in these patients has improved, with 89% of such patients alive and engrafted in the current era compared with 58% in the historical era. The pattern of graft failure has changed from autologous reconstitution, likely secondary to inadequate myelosuppression in the historical era, to aplasia in the current era, likely due to imperfect immunosuppression.

Childhood Cerebral Adrenoleukodystrophy: MR Perfusion Measurements and Their Use in Predicting Clinical Outcome after Hematopoietic Stem Cell Transplantation.

BACKGROUND AND PURPOSE: MR perfusion has shown abnormalities of affected WM in cerebral X-linked adrenoleukodystrophy, but serial data is needed to explore the import of such findings after hematopoietic stem cell transplantation. Our aim was to prospectively measure MR perfusion parameters in patients with cerebral adrenoleukodystrophy pre- and post-hematopoietic stem cell transplantation, and to correlate those measurements with clinical outcome. MATERIALS AND METHODS: Ten patients with cerebral adrenoleukodystrophy prospectively underwent DSC-MR perfusion imaging at <45 days pre- (baseline), 30-60 days post-, and 1 year post-hematopoietic stem cell transplantation. MR perfusion measurements in the 10 patients and 8 controls were obtained from the parieto-occipital WM, splenium of the corpus callosum, leading enhancing edge, and normal-appearing frontal white matter. MR imaging severity scores and clinical neurologic function and neurocognitive scores were also obtained. MR perfusion values were analyzed in the patients with cerebral adrenoleukodystrophy at each time point and compared with those in controls. Correlations were calculated between the pre-hematopoietic stem cell transplantation MR perfusion values and 1-year clinical scores, with P value adjustment for multiple comparisons. RESULTS: At baseline in patients with cerebral adrenoleukodystrophy, both relative CBV and relative CBF within the splenium of the corpus callosum and parieto-occipital WM significantly differed from those in controls (P = .005-.031) and remained so 1 year post-hematopoietic stem cell transplantation (P = .003-.005). Meanwhile, no MR perfusion parameter within the leading enhancing edge differed significantly from that in controls at baseline or at 1 year (P = .074-.999) or significantly changed by 1 year post-hematopoietic stem cell transplantation (P = .142-.887). Baseline Loes scores correlated with 1-year clinical neurologic function (r = 0.813, P < .0001), while splenium of the corpus callosum relative CBV also significantly correlated with 1-year neurologic function scale and the neurocognitive full-scale intelligence quotient and performance intelligence quotient scores (r = -0.730-0.815, P = .007-.038). CONCLUSIONS: Leading enhancing edge measurements likely remain normal post-hematopoietic stem cell transplantation in cerebral adrenoleukodystrophy, suggesting local disease stabilization. Meanwhile, parieto-occipital WM and splenium of the corpus callosum relative CBV and relative CBF values worsened; this change signified irreversible injury. Baseline splenium of the corpus callosum relative CBV may predict clinical outcomes following hematopoietic stem cell transplantation.

Ovarian function after hematopoietic cell transplantation: a descriptive study following the use of GnRH agonists for myeloablative conditioning and observation only for reduced-intensity conditioning.

Gonadal failure is a health and quality-of-life concern in hematopoietic cell transplant (HCT) survivors. While ovarian dysfunction is nearly universal following myeloablative (MA) conditioning, the risk is unclear after reduced-intensity conditioning (RIC). Gonadotropin-releasing hormone agonists decrease ovarian failure rates following conventional chemotherapy, but little is known about its effectiveness with HCT. We investigated the impact of leuprolide on ovarian function after MA conditioning and monitored ovarian function after RIC in this descriptive pilot study. Post-menarchal females <50 years undergoing HCT with adequate baseline ovarian function (follicle-stimulating hormone (FSH) level <40 mIU/mL and normal menstruation) were eligible. Prior to MA conditioning, leuprolide was administered. Those undergoing RIC were observed. FSH was measured at various time points. Seventeen women aged 12-45 years were evaluated (7 in the intervention group and 10 in the observation group). Compared to the historical high rate of ovarian failure after MA conditioning, 3 of 7 evaluable Lupron recipients had ovarian failure at a median of 703 days post transplant. Ovarian failure occurred in 1 of 10 recipients of RIC at a median follow-up of 901 days. In conclusion, leuprolide may protect ovarian function after MA conditioning. Additionally, RIC with cyclophosphamide, fludarabine and low-dose TBI has a low risk of ovarian failure.

Intensity of MRI Gadolinium Enhancement in Cerebral Adrenoleukodystrophy: A Biomarker for Inflammation and Predictor of Outcome following Transplantation in Higher Risk Patients.

BACKGROUND AND PURPOSE: Outcomes following hematopoietic stem cell transplantation for higher risk childhood-onset cerebral adrenoleukodystrophy are variable. We explored whether a brain MR imaging gadolinium intensity scoring system improves prediction of neurologic outcome. MATERIALS AND METHODS: We developed a 4-point scale of gadolinium intensity relative to the choroid plexus: 0 = no enhancement; 1 = hypointense; 2 = isointense; 3 = hyperintense. The interobserver concordance of the scale was assessed on 30 randomly chosen studies. Scores were generated for 64 evaluable patients and compared with CSF chitotriosidase levels, a known inflammatory marker correlating with outcomes following transplantation. For 25 evaluable higher risk patients (Loes ≥10), the gadolinium intensity score was compared with longer term posttransplantation clinical change. RESULTS: The gadolinium intensity scoring system showed good interobserver reproducibility (κ = 0.72). Of 64 evaluable boys, the score positively correlated with average concomitant CSF chitotriosidase activity in nanograms/milliliter/hour: 0: 2717, n = 5; 1: 3218, n = 13; 2: 6497, n = 23; and 3: 12,030, n = 23 (P < .01). For 25 evaluable higher risk patients, more intense pretransplantation brain MR imaging gadolinium enhancement predicted greater average loss on the adrenoleukodystrophy neurologic function scale following transplantation: 0/1: adrenoleukodystrophy neurologic function scale score difference = 4.3, n = 7; 2/3: adrenoleukodystrophy neurologic function scale score difference = 10.4, n = 18 (P = .05). CONCLUSIONS: Gadolinium enhancement intensity on brain MR imaging can be scored simply and reproducibly for cerebral adrenoleukodystrophy. The enhancement score significantly correlates with chitotriosidase. In boys with higher risk cerebral disease (Loes ≥10), the enhancement score itself predicts neurologic outcome following treatment. Such data may help guide treatment decisions for clinicians and families.

Cardiac QTc interval characteristics before and after hematopoietic stem cell transplantation: an analysis of 995 consecutive patients at a single center.

Hematopoietic stem cell transplantation (HSCT) treats disorders affecting patients of all ages. We studied the rate-corrected cardiac QT interval (QTc) in 995 consecutive children and adults undergoing HSCT at the University of Minnesota. We sought to (1) describe QTc before and after HSCT; (2) describe the change in QTc after HSCT; (3) identify factors affecting QTc and its change; and (4) scrutinize an 'at risk' sub-cohort with a long QTc before HSCT. Pre HSCT: 952 (96%) patients had an evaluable electrocardiography (ECG); median QTc was 426 ms and depended upon disease necessitating transplant. Post HSCT: 506 (51%) patients had an evaluable ECG; median QTc was 441 ms. Intrapatient QTc change: 490 (49%) evaluable patients showed median QTc change (pre to post HSCT) of +16 ms (P<0.0001). At risk group: 68 patients were 'at risk' (long pre-HSCT QTc). In some, 'at-risk' status trended toward predictive of post-transplant nonrelapse mortality. QTc interval prolongation is evident in a large, diverse cohort undergoing HSCT at our institution. Prospective studies of this patient population may be warranted, particularly for 'at-risk' patients who demonstrate significant QTc prolongation both pre and post HSCT.

Cardiac arrhythmias and conduction disturbances in the sleep apnea syndrome. Prevalence and significance.

The results of 24-hour continuous electrocardiographic monitoring of 23 patients with documented sleep apnea syndrome were reviewed to evaluate the prevelance of cardiac arrhythmias and conduction disturbances in this disorder. During sleep, marked sinus arrhythmia (more than 30 beats/min variation) was found in 18 patients. Extreme sinus bradycardia (heart rate less than 30 beats/min) and sinus pauses (more than 1.8 sec) were found in only two patients. First-degree and type I second-degree atrioventricular block were found in another patient. There was a decrease in grade of ventricular ectopy from wakefulness to sleep. These data suggest that the prevalence of serious arrhythmias and conduction disturbances during sleep in patients with the sleep apnea syndrome is much lower than previously reported.

Disseminated listeriosis presenting as acute hepatitis. Case reports and review of hepatic involvement in listeriosis.

We report three cases of disseminated listeriosis that presented as acute hepatitis characterized by striking increase of liver function test values and fever. Peak serum transaminases (SGOT) for each of three patients were 5,380, 2,350, and 443 mu/ml respectively. The correct diagnosis was not suspected in any of the patients until blood and cerebrospinal fluid cultures obtained routinely in the course of evaluation for fever grew Listeria monocytogenes. When antibiotic therapy was instituted, serum transaminase values plummeted in two patients; these two were eventually cured of their infection. The third patient succumbed to his infection; postmortem examination showed miliary abscesses of the liver which revealed L. monocytogenes. Review of the literature for previous reports of hepatic involvement in adult patients with listeriosis shows that hepatitis is an unusual mode of presentation. However, since we observed these three cases over a one-year period, we suspect this may not be an uncommon occurrence.

Effect of oral milrinone on end-systolic relations in patients with severe congestive heart failure.

The new inotropic agent milrinone has both vasodilator and inotropic cardiovascular effects, but the importance of these effects in patients with severe congestive heart failure (CHF) is controversial. The left ventricular (LV) end-systolic pressure-diameter relation was used to determine the independent inotropic effect of milrinone. Seven patients with New York Heart Association class III CHF were invasively monitored with right-sided heart catheters and radial arterial lines. M-mode echocardiography was used to measure LV dimensions. The effect of a 10-mg oral dose of milrinone on hemodynamic, echocardiographic and end-systolic variables was determined. End-systolic pressure was measured at the dicrotic notch of the arterial pressure tracing and end-systolic LV dimensions at the time of aortic valve closure. Methoxamine (n = 6) or nitroprusside (n = 1) was used to alter afterload so that the end-systolic pressure-diameter relation could be determined. Arterial vasodilation from milrinone was evidenced by a decrease in mean arterial blood pressure (88 +/- 5 to 77 +/- 2 mm Hg, p less than 0.025) and an increase in cardiac index (from 2.7 +/- 0.2 to 3.2 +/- 0.2 liters/min/m2, p less than 0.025), with no change in heart rate (80 +/- 5 beats/min). Milrinone decreased preload as assessed by the pulmonary artery wedge pressure (from 17 +/- 2 to 10 +/- 2 mm Hg, p less than 0.01) and end-diastolic LV diameter (from 7.4 +/- 0.4 to 7.0 +/- 0.4 cm, p less than 0.025).(ABSTRACT TRUNCATED AT 250 WORDS)

Competitive blood flow in the coronary circulation simulating progression of proximal coronary artery disease after saphenous vein bypass surgery.

We report a case of competitive blood flow in the left coronary circulation after saphenous vein bypass grafting that resulted in the apparent progression of a proximal stenosis to total occlusion at coronary angiography. Repeat angiography with careful attention to catheter position and adequate injection of contrast agent demonstrated the actual anatomy and showed that there was no postoperative change in the native coronary circulation. The true incidence of progression of proximal coronary disease after saphenous vein bypass surgery is unknown, and reported figures may be falsely elevated because of unrecognized competitive flow patterns simulating obstruction.

Bermudagrass sod growth and metal uptake in coal combustion by-product-amended media.

Coal combustion by-products (CCB) include fly ash and bottom ash and are generated nationally at rates of 10(8) Mg yr(-1). Land applications of CCB have improved physicochemical properties of soil, yet inherent bulkiness and trace metal content of CCB often limit their use. Likewise, utilization of biosolids and manure as fertilizer can be problematic due to unfavorable nutrient ratios. A 2-yr field study evaluated environmental and technical parameters associated with CCB-organic waste utilization as growth media in turfgrass sod production. Experimental growth media formulated with CCB and organic waste and a sand-compost control mixture were uniformly spread at rates from 200 to 400 m3 ha(-1) and sprigged with hybrid bermudagrass [Cynodon dactylon (L.) Pers. x C. transvaalensis Burtt-Davy]. Leaf clippings were collected and analyzed for total elemental content each year. In Year 2, growth media samples were collected during establishment 47 and 84 days after planting (DAP) and viable Escherichia coli organisms were quantified. At harvest (99 or 114 DAP), sod biomass and physicochemical properties of the growth media were measured. During sod propagation, micronutrient and metal content in leaf clippings varied by growth media and time. After 47 d of typical sod field management, viable E. coli pathogens were detected in only one biosolids-amended plot. No viable E. coli were measured at 84 DAP. In both years, sod biomass was greatest in media containing biosolids and fly ash. Following installation of sod, evaluations did not reveal differences by media type or application volume. Using CCB-organic waste mixes at the rates described herein is a rapid and environmentally safe method of bermudagrass sod production.

Creatinine production rate measured by whole body counting of 40K.

The creatinine production rate in dialysis patients was measured by potassium-40 whole body counting and carbon-14 creatinine injection. The correlation coefficient for the two methods was 0.96, p less than 0.005. An equation predicting whole body potassium (WBK) for normal subjects was found to accurately predict the WBK of dialysis patients as well. Two equations predicting creatinine production from WBK were compared with measured production rates and were found to agree within experimental error. It is thus possible to use the predictive equations to accurately estimate creatinine production without resorting to experimental measurements. These findings should simplify the use of computer models of the patient-artificial kidney system where accurate estimations of creatinine production rates are essential.

Childhood cerebral X-linked adrenoleukodystrophy: diffusion tensor imaging measurements for prediction of clinical outcome after hematopoietic stem cell transplantation.

BACKGROUND AND PURPOSE: DTI in cerebral X-linked adrenoleukodystrophy may demonstrate abnormalities in both affected and nonaffected WM; these values have not been studied serially after hematopoietic stem cell transplantation. The purpose of this study was to study pretransplant and posttransplant DTI parameters serially and ultimately to determine the ability of pretransplant DTI parameters to predict clinical outcome after HSCT in children with ALD. MATERIALS AND METHODS: Eight patients with posterior-pattern cerebral ALD underwent DTI at 3T before HSCT (T0), at 30-60 days (T1), 90-120 days (T2), 180 days (T3), and 1 year (T4) after HSCT. FA and MD were serially measured in 19 regions, and these measurements were compared with those in control patients. MR imaging severity (Loes) scores were recorded. Correlations were performed between DTI parameters and Loes scores, neurologic function scores, and several neuropsychologic scores. RESULTS: Both FA and MD in subjects differed significantly from that in controls at nearly every time point within cerebellar WM, callosal splenium, and parieto-occipital WM; FA alone was significantly different at each time point within the optic radiations, lateral geniculate, and the Meyer loop (P < .05). Loes scores at T0 correlated strongly with each clinical score at T4 (r = 0.771-0.986, P < .05). The only significant DTI correlation at T0 with a clinical score at T4 was callosal body FA with adaptive function (r = 0.976, P < .001). Correlating the change in DTI values with change in NFS (change between T0 and T4) showed that only ΔMD within the optic radiations correlated strongly with ΔNFS (r = 0.903, P < .05). CONCLUSIONS: DTI values at T0 were generally poor predictors of outcome at 1 year, whereas Loes scores were generally good predictors. ΔMD within the optic radiations strongly correlates with ΔNFS over that year. In addition, certain normal-appearing regions, such as cerebellar WM, may have DTI abnormalities before HSCT that persist after HSCT.

Effect of altered contractility on the linearity of regional left ventricular end-systolic relations in intact hearts.

The purpose of these studies was to determine the effect of altered regional contractility on the linearity of regional left ventricular end-systolic relations. Significant change in the shape of these relations would limit their application as load-independent indices of regional contractility. In a paced, open-chest pig heart preparation (n = 7), the left ventricular end-systolic pressure-segment length relation (ESPLR) and pressure-wall thickness relation (ESPTR) were obtained over a wide range of end-systolic pressures (134 +/- 9 to 70 +/- 6 mm Hg). Regional inotropic state was varied with intracoronary calcium and verapamil. The shapes of the ESPLR and ESPTR were characterized by using linear and quadratic models. Both provided a good fit, although the quadratic model showed a slight concavity to the segment length and thickness axes (second-order coefficient < 0). In the linear model, calcium increased the slope of the ESPLR by 111% (p < 0.01) and the slope of the ESPTR by 170% (p < 0.01). At a pressure of 100 mm Hg, end-systolic segment length (L100) shifted to the left (p < 0.05) and end-systolic wall thickness (T100) to the right (p < 0.025). Verapamil decreased the slope of the ESPLR by 45% (p < 0.01) and of the ESPTR by 33% (p not significant) and produced significant shifts in L100 (p < 0.001) and T100 (p < 0.025). The values of L100 and T100 determined by the quadratic fit were nearly identical to those for the linear fit, and both showed similar significant shifts with altered contractility. There was no significant change in the shape of the quadratic fit (as assessed by the second-order coefficient) with different contractile states. It is concluded that the curvilinearity of the ESPLR and ESPTR under physiologic conditions is slight and appears to be independent of the contractile state. Furthermore, a linear model of regional end-systolic relations can be used to assess regional left ventricular function in intact hearts.

Accumulation of potentially toxic elements in plants and their transfer to human food chain.

Contaminated soils can be a source for crop plants of such elements like As, Cd, Cr, Cu, Ni, Pb, and Zn. The excessive transfer of As, Cu, Ni, and Zn to the food chain is controlled by a "soil-plant barrier"; however, for some elements, including Cd, the soil-plant barrier fails. The level of Cd ingested by average person in USA is about 12 micrograms/day, which is relatively low comparing to Risk Reference Dose (70 micrograms Cd/day) established by USEPA. Food of plant origin is a main source of Cd intake by modern society. Fish and shellfish may be a dominant dietary sources of Hg for some human populations. About half of human Pb intake is through food, of which more than half originates from plants. Dietary intake of Cd and Pb may be increased by application of sludges on cropland with already high levels of these metals. Soils amended with sludges in the USA will be permitted (by USEPA-503 regulations) to accumulate Cr, Cd, Cu, Pb, Hg, Ni, and Se, and Zn to levels from 10 to 100 times the present baseline concentrations. These levels are very permissive by international standards. Because of the limited supply of toxicity data obtained from metals applied in sewage sludge, predictions as to the new regulations will protect crop plants from metal toxicities, and food chain from contamination, are difficult to make.

Anomalous origin of the right coronary high above the left sinus of Valsalva.

Anomalous origin of the right coronary artery from the ascending aorta above the left sinus of Valsalva is exceedingly rare and previously has been reported to be associated with congenital aortic valve disease. We report a case of the right coronary artery arising from the mid ascending aorta, high above the left sinus, with a clinically and angiographically normal aortic valve.