HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Abstract Figures Only Full Text (PDF) Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Quint, L. E. Articles by Deeb, G. M. Search for Related Content PubMed PubMed Citation Articles by Quint, L. E. Articles by Deeb, G. M.

Ulcerlike Lesions of the Aorta: Imaging Features and Natural History¹

¹ From the Departments of Radiology (L.E.Q., D.M.W., I.R.F.) and Surgery, Section of Cardiothoracic Surgery (H.M.M., G.M.D.), and the Consortium for Health Outcomes, Innovation and Cost Effectiveness Studies (CHOICES) (S.S.S., S.P.), University of Michigan Health System, Box 0030, 1500 E Medical Center Dr, Ann Arbor, MI 48109-0030. Received April 3, 2000; revision requested May 25; revision received June 22; accepted August 1. Address correspondence to L.E.Q.

	ABSTRACT

TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION REFERENCES

 
PURPOSE: To document the natural history of ulcerlike aortic lesions and determine whether any computed tomographic (CT) features predict outcome.

MATERIALS AND METHODS: CT scans from 1994 to 1998 that depicted an ulcerlike aortic lesion were retrospectively evaluated. Features evaluated included lesion and aortic size and intramural hematoma. Initial CT findings were correlated with clinical data and subsequent CT findings.

RESULTS: There were 56 lesions in 38 patients. Follow-up (mean, 18.4 months) CT scans were available for 33 lesions. Stability of the lesion and adjacent aorta was noted in 21 lesions. Two lesions were unchanged, although associated intramural hematoma regressed over 1–2 months. Ten lesions showed mild to moderate increase in aortic diameter (mean follow-up, 19.8 months) either with (seven lesions) or without (one lesion) increase in size of the lesion or with incorporation of the lesion into the aortic wall contour (two lesions). Of all 56 lesions, 37 were clinically stable, two were associated with recurrent chest and/or back pain, eight underwent surgical resection or stent placement, and two were in patients who died. Seven lesions were in patients lost to follow-up. No initial CT feature was predictive of CT outcome, although lack of pleural effusion correlated with clinical stability.

CONCLUSION: Most ulcerlike aortic lesions are asymptomatic and do not enlarge. About one-third of lesions progress, generally resulting in mild interval aortic enlargement.

Index terms: Aorta, CT, 563.12112 • Aorta, diseases, 563.74, 563.75 • Aorta, dissection, 56.74, 94.74

	INTRODUCTION

TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION REFERENCES

 
We have observed that ulcerlike aortic projections are not uncommonly visualized on computed tomographic (CT) scans obtained in elderly patients with other evidence of atherosclerotic disease. Although these lesions are usually presumed to represent penetrating atherosclerotic aortic ulcers, histopathologic proof is rarely obtained. In cases with histopathologic proof, there is an atherosclerotic lesion with ulceration that penetrates the internal elastic lamina, often resulting in hematoma within the media of the aortic wall (1). Occasionally, these lesions are seen on CT scans obtained for acute chest pain, although often the lesions are incidental findings observed on CT scans obtained for other reasons.

A penetrating atherosclerotic aortic ulcer may simulate an aortic dissection, both clinically and at imaging. Unlike a typical dissection, however, with penetrating ulcers, the classic double-barrel aorta is generally absent. Instead, intramural hemorrhage usually dissects locally around the ulcer. Rarely, hematoma in the aortic wall (ie, in the false lumen) may rupture back into the aortic true lumen, leading to a classic-appearing dissection with flow in both lumina. Because little is known about the natural history of penetrating ulcers, the implications of detecting such a lesion in a symptomatic or asymptomatic patient are largely unknown. In addition, there is controversy over the appropriate therapy for this condition.

The purpose of our study was to document the natural history of ulcerlike lesions of the aorta identified on CT scans. Furthermore, we aimed to determine whether there were any specific CT features that would help predict subsequent outcome in any individual case.

	MATERIALS AND METHODS

TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION REFERENCES

 
All cases of an ulcerlike lesion of the aorta seen on CT scans at our institution between 1994 and 1998 were retrospectively identified by using computerized searches of the radiology information system. The CT scans were reviewed, and those contrast material–enhanced CT scans that showed one or more focal, well-defined, wide-mouthed, contrast material–filled outpouchings that projected outside the opacified aortic lumen were included in the study. All scans were retrospectively evaluated by one experienced thoracic radiologist (L.E.Q.) with training in cross-sectional imaging.

The initial CT scan, as well as any follow-up scans, were evaluated for the following features: lesion location, lesion width and length, aortic diameter at the level of the lesion, intramural hematoma, presence and length of the false lumen, contrast material opacification of the false lumen, mediastinal hematoma, and pleural effusion.

CT examinations were performed with a variety of scanners. Those performed at our institution involved helical scanning with thin collimation (3–5 mm) and a 150– 200-mL bolus of intravenous contrast material (iohexol 300 [Omnipaque]; Nycomed Amersham, New York, NY) administered at 3 mL/sec. Patients who were referred from outside institutions often had their initial studies performed at those outside centers, with variable techniques. Only intravenous contrast–enhanced studies were evaluated.

Patient charts were reviewed by an experienced thoracic surgery nurse (H.M.M.) (who was also familiar with many of the individual patients) to obtain correlative clinical information corresponding to the dates of the CT studies as well as long-term follow-up. Approval of the institutional review board was obtained for chart review; informed consent from patients was waived.

Lesions were assigned to one of the following CT outcome categories based on change or stability in lesion appearance and lesion and aortic diameter measurements (change, >5%): stable, progression, or regression. Lesions were also assigned to one of the following clinical outcome categories based on notes in the clinical chart: stable (ie, asymptomatic on medical therapy), chest and/or back pain, surgical or endograft treatment, or death.

A ² analysis was used to determine whether any clinical parameters (including sex, age, presence of hypertension, or symptoms at presentation) or any CT features on the initial CT scan were predictive of clinical outcome (stable or pain/surgery/death) or CT outcome (progression or stable/regression).

	RESULTS

TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION REFERENCES

 
Thirty-eight patients with a total of 56 ulcerlike lesions of the aorta on CT scans were identified. Twenty-six patients had one lesion, seven patients had two lesions, four patients had three lesions, and one patient had four lesions. The mean patient age was 72 years (range, 55–95 years). There were 20 men and 18 women. Twenty-one patients presented with acute chest or back pain, and one presented with acute shortness of breath. The lesion was an incidental finding on a CT scan obtained for other medical reasons in 16 asymptomatic patients. One lesion was located in the ascending aorta, 14 in the aortic arch (including the horizontally oriented portion of the aorta immediately distal to the left subclavian artery), 15 in the proximal descending aorta, 20 in the distal descending aorta, and six in the abdominal aorta. A single CT scan was available in 23 cases, whereas multiple CT scans were available in 33 cases. Initial imaging findings for all 56 lesions are listed in Table 1.

View larger version (114K): [in this window] [in a new window] [Download PPT slide]   Figure 1. Stable ulcerlike lesion of the distal aortic arch. Initial transverse CT scan shows the ulcerlike lesion (U), as well as a small intramural hematoma (arrows) and displaced intimal calcifications (arrowhead). CT scan obtained 10 months later (not shown) revealed no definite change.

View larger version (125K): [in this window] [in a new window] [Download PPT slide]   Figure 2a. Ulcerlike lesion of the distal thoracic aorta with decrease in intramural hematoma over time. (a) Initial transverse CT scan reveals an ulcerlike aortic lesion (U), intramural hematoma (arrows), and bilateral pleural effusions (E). (b) Transverse CT scan obtained 5 weeks later shows slight interval decrease in the thickness of the intramural hematoma, without substantial change in the size of the ulcer. Pleural effusions have resolved.

View larger version (117K): [in this window] [in a new window] [Download PPT slide]   Figure 2b. Ulcerlike lesion of the distal thoracic aorta with decrease in intramural hematoma over time. (a) Initial transverse CT scan reveals an ulcerlike aortic lesion (U), intramural hematoma (arrows), and bilateral pleural effusions (E). (b) Transverse CT scan obtained 5 weeks later shows slight interval decrease in the thickness of the intramural hematoma, without substantial change in the size of the ulcer. Pleural effusions have resolved.

View larger version (94K): [in this window] [in a new window] [Download PPT slide]   Figure 3a. Enlarging ulcerlike lesion of the aortic arch with increase in aortic diameter. (a) Initial transverse CT scan shows an ulcerlike lesion (U), intramural hematoma (arrows), and displaced intimal calcifications (arrowhead). (b) Transverse CT scan obtained 19 months later shows interval increase in size of the lesion, increase in aortic diameter, and near-complete resolution of intramural hematoma.

View larger version (91K): [in this window] [in a new window] [Download PPT slide]   Figure 3b. Enlarging ulcerlike lesion of the aortic arch with increase in aortic diameter. (a) Initial transverse CT scan shows an ulcerlike lesion (U), intramural hematoma (arrows), and displaced intimal calcifications (arrowhead). (b) Transverse CT scan obtained 19 months later shows interval increase in size of the lesion, increase in aortic diameter, and near-complete resolution of intramural hematoma.

View larger version (183K): [in this window] [in a new window] [Download PPT slide]   Figure 4a. Mild enlargement of descending thoracic aortic ulcerlike lesion with mild aortic enlargement. (a) Initial transverse CT scan shows an ulcerlike lesion (U) of the aorta. Adjacent low-attenuating material (H), consistent with hematoma, appears to lie within the aortic wall, as well as partially within the aortic lumen and within mediastinal fat (arrow). (b) Transverse CT scan obtained 25 months later shows mild interval enlargement of both the ulcerlike lesion and the aorta, with slight decrease in adjacent hematoma.

View larger version (182K): [in this window] [in a new window] [Download PPT slide]   Figure 4b. Mild enlargement of descending thoracic aortic ulcerlike lesion with mild aortic enlargement. (a) Initial transverse CT scan shows an ulcerlike lesion (U) of the aorta. Adjacent low-attenuating material (H), consistent with hematoma, appears to lie within the aortic wall, as well as partially within the aortic lumen and within mediastinal fat (arrow). (b) Transverse CT scan obtained 25 months later shows mild interval enlargement of both the ulcerlike lesion and the aorta, with slight decrease in adjacent hematoma.

View larger version (116K): [in this window] [in a new window] [Download PPT slide]   Figure 5a. Incorporation of ulcerlike lesion into aortic contour, with concomitant aortic enlargement. (a) Initial transverse CT scan reveals an ulcerlike lesion (U) of the proximal descending aorta with intramural hematoma (H). (Adjacent images [not shown] revealed displaced intimal calcifications.) (b) Transverse CT scan obtained 16 months later shows fusiform dilatation of the aorta with loss of definition of the ulcer.

View larger version (141K): [in this window] [in a new window] [Download PPT slide]   Figure 5b. Incorporation of ulcerlike lesion into aortic contour, with concomitant aortic enlargement. (a) Initial transverse CT scan reveals an ulcerlike lesion (U) of the proximal descending aorta with intramural hematoma (H). (Adjacent images [not shown] revealed displaced intimal calcifications.) (b) Transverse CT scan obtained 16 months later shows fusiform dilatation of the aorta with loss of definition of the ulcer.

View larger version (105K): [in this window] [in a new window] [Download PPT slide]   Figure 6a. Coalescence of adjacent small ulcers into a larger saccular aneurysm. (a) Initial transverse CT scan shows several small ulcerlike lesions (arrows) protruding off the bottom of the aortic arch, with adjacent intramural and/or mediastinal hematoma (H). (b) Follow-up transverse CT scan obtained 23 months later shows that two of the lesions have coalesced into a larger contrast material-containing cavity, with little or no change in the adjacent hematoma.

View larger version (104K): [in this window] [in a new window] [Download PPT slide]   Figure 6b. Coalescence of adjacent small ulcers into a larger saccular aneurysm. (a) Initial transverse CT scan shows several small ulcerlike lesions (arrows) protruding off the bottom of the aortic arch, with adjacent intramural and/or mediastinal hematoma (H). (b) Follow-up transverse CT scan obtained 23 months later shows that two of the lesions have coalesced into a larger contrast material-containing cavity, with little or no change in the adjacent hematoma.

Two of the 56 lesions occurred in patients who died shortly following diagnosis, without follow-up CT scanning. The cause of death in these two patients was acute renal failure in one and sepsis, hypotension, chronic liver failure, and acute renal failure in the other. It is unclear what role the ulcers played in these deaths. The remaining seven of the 56 lesions were in patients who were subsequently lost to clinical follow-up.

Predictors of Outcome
The only CT feature predictive of clinical outcome was lack of pleural effusion; this feature showed a statistically significant correlation with clinical stability of the aortic lesion (P = .002). No CT feature showed a statistically significant correlation with CT outcome (P > .05). No statistically significant correlation was found between any presenting clinical feature and clinical or CT outcome (P > .05).

	DISCUSSION

TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION REFERENCES

 
Our search of the medical literature revealed little published information regarding the natural history of aortic ulcers. Harris et al (2) studied 29 penetrating atherosclerotic aortic ulcers that were diagnosed with use of CT, magnetic resonance imaging, or aortography in 18 patients. No histopathologic proof was obtained for 28 of the 29 aortic lesions. Clinical and imaging follow-up, from 1 to 6 years, was available in 10 patients (17 ulcers). Two patients had recurrent pain, one had recurrent embolization, and seven were asymptomatic. Imaging showed no change over time for nine ulcers and progression to a saccular aneurysm for four ulcers. In four patients, concentric aortic dilatation developed, with loss of definition of the ulcer crater, showing an average aortic growth rate of 0.33 cm/y or 10%/y. The authors postulated that penetrating atherosclerotic ulcers lead to local weakening of the aortic media, resulting in aortic dilatation. They also theorized that most saccular aneurysms of the aorta that are caused by atherosclerotic disease probably originate from penetrating ulcers. The results of their study were similar to ours in that most lesions were stable, although fusiform aortic dilatation was a common sequela. They found a somewhat higher rate of development of saccular aneurysms, although the small sample sizes in both studies may make these differences statistically insignificant.

A recent pictorial essay depicting presumed penetrating ulcers (without histopathologic proof) showed two that progressed to pseudoaneurysms or saccular aneurysms, one over a 2-week period and the other over an 18-month interval (3). The frequency of aneurysm development was unclear from that essay and may suggest that surgery is often necessary. However, the results of our study suggest that a conservative approach suffices in most cases. An additional imaging study of penetrating ulcers, with follow-up in four patients for 4 weeks to 8 months, showed full or partial resolution of intramural hematoma in all patients (4). The ulcer became incorporated into the wall of an ectatic aorta in three patients, and one patient developed a focal contained perforation or pseudoaneurysm.

In another recent study, also without histopathologic proof, the authors evaluated serial CT scans obtained in 32 patients with intramural hematoma of the aorta (5). Ulcerlike projections were observed in six patients (six lesions) on the initial study and in 14 additional patients (15 lesions) during the follow-up period. Eight of these 21 ulcerlike projections disappeared on subsequent follow-up scans. Ulcerlike projections in 12 patients progressed to saccular aneurysms between 7 days and 7 months after onset. Three patients with saccular aneurysms underwent surgery, and one died owing to rupture of the aneurysm. One patient with an ulcerlike projection developed a frank type A dissection and required surgery. These authors found more rapid progression of aneurysms and a higher tendency to develop saccular aneurysms as compared with our findings. Therefore, the ulcerlike projections developing in a previously formed intramural hematoma may be different lesions, as compared with the ulcerlike lesions identified in our patient population. The authors suggested that the ulcerlike projections appearing on follow-up studies in their patients with intramural hematoma may have represented intimal tears due to hydraulic stress. In contrast, many of the lesions in our series probably represented penetrating atheromatous ulcers, on the basis of clinical and imaging findings.

Limitations of our study included lack of histopathologic proof for the aortic lesions we evaluated. Therefore, we elected to call the lesions "ulcerlike lesions of the aorta" rather than penetrating atherosclerotic ulcers. In fact, most cases reported in the medical literature regarding the imaging appearance and clinical features of so-called penetrating atherosclerotic ulcers do not have histopathologic proof, and the diagnosis is assumed but unconfirmed (1–5). Thus, it is entirely possible that some of the lesions in our study, as well as in other published studies, may have represented different entities, such as an atypical dissection with an intimal tear and intramural hematoma; an aneurysm with irregular, atherosclerotic debris; a branch vessel pseudoaneurysm; a contained aortic rupture; or spontaneous intramural hematoma without intimal tear. Further radiologic-histopathologic correlation studies may shed light on this problem.

Other limitations of our study included the relatively small sample size, which limited statistical analysis. However, our study included imaging and clinical follow-up on a larger group of patients than that in any published study in the English-language literature, to our knowledge. Another potential limitation was the difficulty in obtaining accurate measurements on small ulcers, given the CT techniques available at the time these patients were scanned. This might lead to inaccuracies in assessing for interval change. Due to the retrospective nature of this study, there may have been some selection bias involved. For example, the search methods we used may not have identified all patients with ulcerlike lesions who underwent scanning during the specified time period, particularly if the original interpreting radiologist did not include the term "ulcer" in the official report.

In conclusion, we have found that most ulcerlike aortic lesions remain unchanged over time and do not cause symptoms, although about one-third of lesions progress, generally resulting in mild interval aortic enlargement. Therefore, surgical resection or endograft placement is not necessary in most patients. Infrequently, the lesion may progress to a saccular aneurysm, generally with concomitant aortic ectasia. Because lack of symptoms does not necessarily imply lesion stability, we follow up these patients with CT imaging in the same fashion as we do for those with thoracic aortic aneurysms.

	FOOTNOTES

 
Author contributions: Guarantor of integrity of entire study, L.E.Q.; study concepts, G.M.D., S.P., S.S.S., I.R.F., D.M.W., L.E.Q.; study design, G.M.D., H.M.M., I.R.F., D.M.W., L.E.Q.; definition of intellectual content, G.M.D., I.R.F., D.M.W., L.E.Q.; literature research, L.E.Q.; clinical studies, I.R.F., D.M.W., L.E.Q.; data acquisition, H.M.M., L.E.Q.; data analysis, G.M.D., S.P., S.S.S., I.R.F., D.M.W., L.E.Q.; statistical analysis, S.S.S., S.P.; manuscript preparation, H.M.M., I.R.F., D.M.W., L.E.Q.; manuscript editing, G.M.D., I.R.F., D.M.W., L.E.Q.; manuscript review and final version approval, all authors.

	REFERENCES

TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION REFERENCES

 

1. Stanson A, Kazmier F, Hollier L, et al. Penetrating atherosclerotic ulcers of the thoracic aorta: natural history and clinicopathologic correlations. Ann Vasc Surg 1986; 1:15-23.[Medline]
2. Harris J, Bis K, Glover J, Bendick P, Shetty A, Brown O. Penetrating atherosclerotic ulcers of the aorta. J Vasc Surg 1994; 19:90-99.[Medline]
3. Levy J, Heiken J, Gutierrez F. Imaging of penetrating atherosclerotic ulcers of the aorta. AJR Am J Roentgenol 1999; 173:151-154.[Free Full Text]
4. Kazerooni E, Bree R, Williams D. Penetrating atherosclerotic ulcers of the descending thoracic aorta: evaluation with CT and distinction from aortic dissection. Radiology 1992; 183:759-765.[Abstract/Free Full Text]
5. Sueyoshi E, Matsuoka Y, Sakamoto I, et al. Fate of intramural hematoma of the aorta: CT evaluation. J Comput Assist Tomogr 1997; 21:931-938.[Medline]

This article has been cited by other articles:

				Y. Tsuji, Y. Okita, K. Sugimoto, T. Yamashita, Y. Hino, H. Tanaka, T. Taniguchi, and M. Matsumori Multiple Penetrating Atherosclerotic Ulcers of the Aorta: Report of a Case Vascular and Endovascular Surgery, January 1, 2007; 40(6): 495 - 498. [Abstract] [PDF]

				R. G. Hayter, J. T. Rhea, A. Small, F. S. Tafazoli, and R. A. Novelline Suspected Aortic Dissection and Other Aortic Disorders: Multi-Detector Row CT in 373 Cases in the Emergency Setting Radiology, March 1, 2006; 238(3): 841 - 852. [Abstract] [Full Text] [PDF]

				G. Garzon, M. Fernandez-Velilla, M. Marti, I. Acitores, F. Ybanez, and L. Riera Endovascular Stent-Graft Treatment of Thoracic Aortic Disease RadioGraphics, October 1, 2005; 25(suppl_1): S229 - S244. [Abstract] [Full Text] [PDF]

				B. FURLOW Aortic Emergencies Radiol. Technol., September 1, 2005; 77(1): 41 - 49. [Abstract] [Full Text] [PDF]

				A. Evangelista, R. Dominguez, C. Sebastia, A. Salas, G. Permanyer-Miralda, G. Avegliano, Z. Gomez-Bosh, T. Gonzalez-Alujas, H. Garcia del Castillo, and J. Soler-Soler Prognostic value of clinical and morphologic findings in short-term evolution of aortic intramural haematoma: Therapeutic implications Eur. Heart J., January 1, 2004; 25(1): 81 - 87. [Abstract] [Full Text] [PDF]

				P. Demers, D. C. Miller, R. S. Mitchell, S. T. Kee, L. Chagonjian, and M. D. Dake Stent-graft repair of penetrating atherosclerotic ulcers in the descending thoracic aorta: mid-term results Ann. Thorac. Surg., January 1, 2004; 77(1): 81 - 86. [Abstract] [Full Text] [PDF]

				E. Castaner, M. Andreu, X. Gallardo, J. M. Mata, M. A. Cabezuelo, and Y. Pallardo CT in Nontraumatic Acute Thoracic Aortic Disease: Typical and Atypical Features and Complications RadioGraphics, October 1, 2003; 23(90001): S93 - 110. [Abstract] [Full Text] [PDF]

				A. Evangelista, R. Dominguez, C. Sebastia, A. Salas, G. Permanyer-Miralda, G. Avegliano, C. Elorz, T. Gonzalez-Alujas, H. Garcia Del Castillo, and J. Soler-Soler Long-Term Follow-Up of Aortic Intramural Hematoma: Predictors of Outcome Circulation, August 5, 2003; 108(5): 583 - 589. [Abstract] [Full Text] [PDF]

				K. J. Macura, F. M. Corl, E. K. Fishman, and D. A. Bluemke Pathogenesis in Acute Aortic Syndromes: Aortic Dissection, Intramural Hematoma, and Penetrating Atherosclerotic Aortic Ulcer Am. J. Roentgenol., August 1, 2003; 181(2): 309 - 316. [Full Text] [PDF]

				E. Sueyoshi, Y. Matsuoka, T. Imada, T. Okimoto, I. Sakamoto, and K. Hayashi New Development of an Ulcerlike Projection in Aortic Intramural Hematoma: CT Evaluation Radiology, August 1, 2002; 224(2): 536 - 541. [Abstract] [Full Text] [PDF]

				J. Sailer, P. Peloschek, T. Rand, M. Grabenwoger, S. Thurnher, and J. Lammer Endovascular Treatment of Aortic Type B Dissection and Penetrating Ulcer Using Commercially Available Stent-Grafts Am. J. Roentgenol., December 1, 2001; 177(6): 1365 - 1369. [Abstract] [Full Text] [PDF]

				A. J. Madureira, L. E. Quint, and D. M. Williams Diagnostic Criteria for Intramural Hematoma Drs Quint and Williams respond: Radiology, February 1, 2002; 222(2): 576 - 577. [Full Text] [PDF]

This Article Abstract Figures Only Full Text (PDF) Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Quint, L. E. Articles by Deeb, G. M. Search for Related Content PubMed PubMed Citation Articles by Quint, L. E. Articles by Deeb, G. M.