Herbert S. Schwartz

Vanderbilt University, Нашвилл, Michigan, United States

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Publications (185)623.03 Total impact

  • Herbert S. Schwartz · Ginger E. Holt

    No preview · Chapter · Dec 2015
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    ABSTRACT: and Objective . Sarcopenia is associated with decreased survival and increased complications in carcinoma patients. We hypothesized that sarcopenic soft-tissue sarcoma (STS) patients would have decreased survival, increased incidence of wound complications, and increased length of postresection hospital stay (LOS). Methods . A retrospective, single-center review of 137 patients treated surgically for STS was conducted. Sarcopenia was assessed by measuring the cross-sectional area of bilateral psoas muscles (total psoas muscle area, TPA) at the level of the third lumbar vertebrae on a pretreatment axial computed tomography scan. TPA was then adjusted for height (cm 2 /m 2 ). The association between height-adjusted TPA and survival was assessed using Cox proportional hazard model. A logistical model was used to assess the association between height-adjusted TPA and wound complications. A linear model was used to assess the association between height-adjusted TPA and LOS. Results . Height-adjusted TPA was not an independent predictor of overall survival ( p = 0.746 ). Patient age ( p = 0.02 ) and tumor size ( p = 0.009 ) and grade ( p = 0.001 ) were independent predictors of overall survival. Height-adjusted TPA was not a predictor of increased hospital LOS ( p = 0.66 ), greater incidence of postoperative infection ( p = 0.56 ), or other wound complications ( p = 0.14 ). Conclusions . Sarcopenia does not appear to impact overall survival, LOS, or wound complications in patients with STS.
    No preview · Article · Dec 2015 · Sarcoma
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    Full-text · Dataset · Nov 2015

  • No preview · Article · Sep 2015
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    ABSTRACT: Bone formation during fracture repair inevitably initiates within or around extravascular deposits of a fibrin-rich matrix. In addition to a central role in hemostasis, fibrin is thought to enhance bone repair by supporting inflammatory and mesenchymal progenitor egress into the zone of injury. However, given that a failure of efficient fibrin clearance can impede normal wound repair, the precise contribution of fibrin to bone fracture repair, whether supportive or detrimental, is unknown. Here, we employed mice with genetically and pharmacologically imposed deficits in the fibrin precursor fibrinogen and fibrin-degrading plasminogen to explore the hypothesis that fibrin is vital to the initiation of fracture repair, but impaired fibrin clearance results in derangements in bone fracture repair. In contrast to our hypothesis, fibrin was entirely dispensable for long-bone fracture repair, as healing fractures in fibrinogen-deficient mice were indistinguishable from those in control animals. However, failure to clear fibrin from the fracture site in plasminogen-deficient mice severely impaired fracture vascularization, precluded bone union, and resulted in robust heterotopic ossification. Pharmacological fibrinogen depletion in plasminogen-deficient animals restored a normal pattern of fracture repair and substantially limited heterotopic ossification. Fibrin is therefore not essential for fracture repair, but inefficient fibrinolysis decreases endochondral angiogenesis and ossification, thereby inhibiting fracture repair.
    Full-text · Article · Jul 2015 · The Journal of clinical investigation
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    ABSTRACT: Background: The prevalence and cost of unnecessary advanced imaging studies (AIS) in the evaluation of long bone cartilaginous lesions have not been studied previously. Methods: A total of 105 enchondromas and 19 chondrosarcomas arising in long bones from July 2008 until April 2012 in 121 patients were reviewed. Advanced imaging was defined as MRI, CT, bone scan, skeletal survey, or CT biopsy. Two blinded radiologists independently reviewed the initial imaging study and determined if further imaging was indicated based on that imaging study alone. The cost of imaging was taken from our institution's global charge list. Imaging was deemed unnecessary if it was not recommended by our radiologists after review of the initial imaging study. The difference in cost was calculated by subtracting the cost of imaging recommended by each radiologist from the cost of unnecessary imaging. The sensitivity and specificity for distinguishing enchondromas from chondrosarcomas was calculated. A minimum of 2 years from diagnosis of an enchondroma was required to monitor for malignant transformation. Results: Of patients diagnosed with an enchondroma, 85 % presented with AIS. The average enchondroma patient presented with one unnecessary AIS. The radiologists' interpretations agreed 85 % of the time for enchondromas and 100 % for chondrosarcomas. The sensitivity and specificity for distinguishing enchondromas from chondrosarcomas was 95 % for one radiologist and 87 and 95 % for the other. The average unnecessary cost per enchondroma patient was $1,346.18. Conclusions: Unnecessary AIS are frequently performed and are a significant source of expense. The imaging algorithms outlined in this study may reduce unnecessary AIS.
    No preview · Article · Jan 2015 · Annals of Surgical Oncology
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    ABSTRACT: Background We reviewed medico-legal cases related to extremity sarcoma malpractice in order to recognize those factors most commonly instigating sarcoma litigation.Methods Over one million legal cases available in a national legal database were searched for malpractice verdicts and settlements involving extremity sarcoma spanning 1980–2012. We categorized verdict/settlement resolutions by state, year, award amount, nature of the complaint/injury, specialty of the physician defendant, and academic affiliation of defendant–amongst other variables.ResultsOf the 216 cases identified, 57% of case resolutions favored the plaintiff, with a mean indemnity payment of $2.30 million (range $65,076–$12.66 million). Delay in diagnosis (81%), unnecessary amputation (11%), and misdiagnosis (7%) accounted for the majority of complaints. The greatest numbers of claims were filed against primary care specialties (34%), orthopaedic surgeons (23%), and radiologists (12%). Individual state tort reform measures were not protective against case resolution outcome.Conclusions Reported medico-legal claims involving sarcoma care continue to rise, with mean indemnity payments approaching 10 times that for other reported medical/surgical specialties. Primary care and orthopaedic specialties are the most commonly named physician defendants, citing a delay in diagnosis. This suggests further education in the front line diagnosis and management of sarcomas is needed. J. Surg. Oncol. © 2014 Wiley Periodicals, Inc.
    No preview · Article · Dec 2014 · Journal of Surgical Oncology
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    ABSTRACT: Underlying vascular disease is an important pathophysiologic factor shared among many co-morbid conditions associated with poor fracture healing, such as diabetes, obesity, and age. Determining the temporal and spatial patterns of revascularization following fracture is essential for devising therapeutic strategies to augment this critical reparative process. Seminal studies conducted in the last century have investigated the pattern of vascularity in bone following fracture. The consensus model culminating from these classical studies depicts a combination of angiogenesis emanating from both the intact intramedullary and periosteal vasculature. Subsequent to the plethora of experimental fracture angiography in the early to mid-20th century there has been a paucity of reports describing the pattern of revascularization of a healing fracture. Consequently the classical model of revascularization of a displaced fracture has remained largely unchanged. Here, we have overcome the limitations of animal fracture models performed in the above described classical studies by combining novel techniques of bone angiography and a reproducible murine femur fracture model to demonstrate for the first time the complete temporal and spatial pattern of revascularization in a displaced/stabilized fracture. These studies were designed specifically to i) validate the classical model of fracture revascularization of a displaced/stabilized fracture ii) assess the association between intramedullary and periosteal angiogenesis and iii) elucidate the expression of VEGF/VEGF-R in relation to the classical model. From the studies, in conjunction with classic studies of angiogenesis during fracture repair, we propose a novel model (see abstract graphic) that defines the process of bone revascularization subsequent to injury to guide future approaches to enhance fracture healing. This new model validates and advances the classical model by providing evidence that during the process of revascularization of a displaced fracture 1) periosteal angiogenesis occurs in direct communication with the remaining intact intramedullary vasculature as a result of a vascular shunt and 2) vascular union occurs through an intricate interplay between intramembranous and endochondral VEGF/VEGF-R mediated angiogenesis.
    Full-text · Article · Oct 2014 · Bone
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    ABSTRACT: Background and Objectives In 2002, with the advent of better classification techniques, the World Health Organization declassified malignant fibrous histiocytoma (MFH) as a distinct histological entity in favor of the reclassified entity high-grade undifferentiated pleomorphic sarcoma (HGUPS). To date, no study has evaluated comparative outcomes between patients designated historically in the MFH group and those classified in the new HGUPS classification. Our goal was to determine the presence of clinical prognostic implications that have evolved with this new nomenclature.Methods Sixty-eight patients were retrospectively evaluated between January 1998 and December 2007. Forty-five patients diagnosed with MFH between 1998 and 2003 were compared to 23 patients in the HGUPS group, from 2004 to 2007. Primary prognostic outcomes assessed included overall survival, metastatic-free, and local recurrence-free survival.ResultsFive-year survivorship between MFH and HGUPS populations, using Kaplan–Meier or competing risk methods, did not show statistical difference for overall survival (60% vs. 74%, P = 0.36), 5-year metastasis-free survival (31% vs. 26%, P = 0.67), or local recurrence-free survival (13% vs. 16%, P = 0.62).Conclusion Despite new classification nomenclature, there appears to be no identifiable prognostic implications for sarcomas that remain in the unclassifiable HGUPS group, as compared to the previously accepted MFH group. J. Surg. Oncol. © 2014 Wiley Periodicals, Inc.
    No preview · Article · Sep 2014 · Journal of Surgical Oncology
  • April C Pettit · Martin B Raynor · Herbert S Schwartz · Patty W Wright

    No preview · Article · Jul 2014
  • Vignesh K Alamanda · David C Moore · Yanna Song · Herbert S Schwartz · Ginger E Holt
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    ABSTRACT: Obesity is a growing epidemic and has been associated with an increased frequency of complications after various surgical procedures. Studies also have shown adipose tissue to promote a microenvironment favorable for tumor growth. Additionally, the relationship between obesity and prognosis of soft tissue sarcomas has yet to be evaluated.
    No preview · Article · Jun 2014 · Clinical Orthopaedics and Related Research
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    ABSTRACT: Radiographic imaging plays a crucial role in the diagnosis of osteosarcoma. Currently, computed-tomography (CT) is used to measure tumor-induced osteolysis as a marker for tumor growth by monitoring the bone fractional volume. As most tumors primarily induce osteolysis, lower bone fractional volume has been found to correlate with tumor aggressiveness. However, osteosarcoma is an exception as it induces osteolysis and produces mineralized osteoid simultaneously. Given that competent bone is highly anisotropic (systematic variance in its architectural order renders its physical properties dependent on direction of load) and that tumor induced osteolysis and osteogenesis are structurally disorganized relative to competent bone, we hypothesized that μCT-derived measures of anisotropy could be used to qualitatively and quantitatively detect osteosarcoma provoked deviations in bone, both osteolysis and osteogenesis, in vivo. We tested this hypothesis in a murine model of osteosarcoma cells orthotopically injected into the tibia. We demonstrate that, in addition to bone fractional volume, μCT-derived measure of anisotropy is a complete and accurate method to monitor osteosarcoma-induced osteolysis. Additionally, we found that unlike bone fractional volume, anisotropy could also detect tumor-induced osteogenesis. These findings suggest that monitoring tumor-induced changes in the structural property isotropy of the invaded bone may represent a novel means of diagnosing primary and metastatic bone tumors.
    Full-text · Article · Jun 2014 · PLoS ONE
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    ABSTRACT: IntroductionThe standard of care for extremity soft tissue sarcomas continues to be negative-margin limb salvage surgery. Radiotherapy is frequently used as an adjunct to decrease local recurrence. No differences in survival have been found between preoperative and postoperative radiotherapy regimens. However, it is uncertain if the use of a postoperative boost in addition to preoperative radiotherapy reduces local recurrence rates.Methods This retrospective review evaluated patients who received preoperative radiotherapy (n = 49) and patients who received preoperative radiotherapy with a postoperative boost (n = 45). The primary endpoint analysed was local recurrence, with distant metastasis and death due to sarcoma analysed as secondary endpoints. Wilcoxon rank-sum test and either χ2 or Fisher's exact test were used to compare variables. Multivariable regression analyses were used to take into account potential confounders and identify variables that affected outcomes.ResultsNo differences in the proportion or rate of local recurrence, distant metastasis or death due to sarcoma were observed between the two groups (P > 0.05). The two groups were similarly matched with respect to demographics such as age, race and sex and tumour characteristics including excision status, tumour site, size, depth, grade, American Joint Committee on Cancer stage, chemotherapy receipt and histological subtype (P > 0.05). The postoperative boost group had a larger proportion of patients with positive microscopic margins (62% vs 10%; P < 0.001).Conclusion No differences in rates of local recurrence, distant metastasis or death due to sarcoma were found in patients who received both pre- and postoperative radiotherapy when compared with those who received only preoperative radiotherapy.
    No preview · Article · Jun 2014 · Journal of Medical Imaging and Radiation Oncology
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    ABSTRACT: Osteosarcoma is the most common primary malignant tumor of bone, and accounts for around 50% of all primary skeletal malignancies. In addition to novel chemotherapies, there is a need for adjuvant therapies designed to inhibit osteosarcoma proliferation and tumor-induced osteolysis to attenuate tumor expansion and metastasis. As such, studies on the efficacy of bisphosphonates on human osteosarcoma are planned following feasibility studies which determined that the bisphosphonate zoledronic-acid (ZOL) can be safely combined with conventional chemotherapy (1). However, the molecular mechanisms responsible for, and means of inhibiting, osteosarcoma-induced osteolysis are largely unknown. We establish that osteosarcoma growth directly correlates with tumor-induced osteolysis and activation of osteoclasts in-vivo. In-vitro, tumor cells were determined to expresses surface, but not soluble, RANKL and stimulated osteoclastogenesis in a manner directly proportional to their malignant potential. In addition, an aggressive osteosarcoma cell line was shown to secrete monocyte chemoattractant protein-1 (MCP-1) resulting in robust monocyte migration. Since MCP-1 is a key cytokine for monocyte recruitment and surface bound RANKL strongly supports local osteoclastogenesis, we suggest that high levels of these signaling molecules are associated with the aggressive potential of osteosarcoma. Consistent with these findings, abundant expression of RANKL/MCP-1 was observed in tumor in-vivo, and MCP-1 plasma levels strongly correlated with tumor progression and osteolysis. ZOL administration directly attenuates osteosarcoma production of RANKL/MCP-1, reducing tumor-induced bone destruction. In vivo, these findings also correlated with significant reduction in osteosarcoma growth. ZOL attenuates tumor-induced osteolysis, not only through direct inhibition of osteoclasts, but also through direct actions on tumor expression of osteoclast activators. These data provide insight regarding the effect of ZOL on osteosarcoma essential for designing the planned upcoming prospective randomized trials to determine the efficacy of bisphosphonates on osteosarcoma in humans. © 2014 American Society for Bone and Mineral Research.
    Full-text · Article · Jun 2014 · Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research
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    ABSTRACT: Unlabelled: Osteosarcoma is the most common primary bone malignancy and accounts for more than half of primary skeletal malignancies in children and young adults. Although vascular endothelial growth factor (VEGF) expression in osteosarcoma has been associated with poor outcome, its role in the pathogenesis of osteosarcoma remains controversial. Here, VEGF and VEGFR1 expression in both human and murine osteosarcoma cells associated with increasing malignant potential. Autocrine VEGF/VEGFR1 signaling resulted in constitutive activation of VEGFR1 in highly aggressive osteosarcoma cells. In addition, survival and proliferation of highly aggressive osteosarcoma cells was dependent on autocrine VEGF/R1 signaling in vitro. The effect of VEGFR1 expression on in vivo tumor growth and angiogenesis was evaluated by immunoselecting subpopulations of osteosarcoma cells that express high or low levels of VEGFR1. Cell enriched for high VEGFR1 expression showed increased VEGF production, tumor growth, tumor angiogenesis, and osteolysis in vivo. In addition, it was demonstrated that VEGF and VEGFR1 are coexpressed by a subset of tumor cells in human osteosarcoma, similar to what was observed in the murine osteosarcoma cells. These results suggest that autocrine VEGF/VEGFR1 signaling in a subpopulation of tumor cells plays a pivotal role in osteosarcoma progression. Implications: Aggressive osteosarcoma phenotypes are mediated by autocrine VEGF/VEGFR1 signaling and improved stratification measures and novel anti-angiogenic strategies may benefit this specific tumor type.
    Full-text · Article · Apr 2014 · Molecular Cancer Research
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    ABSTRACT: Prior studies have demonstrated postoperative infection may confer a survival benefit after osteosarcoma resection. Our aim was to determine whether infection after soft tissue sarcoma resection has similar effects on metastasis, recurrence and survival. A retrospective review was conducted; 396 patients treated surgically for a soft tissue sarcoma between 2000 and 2008 were identified. Relevant oncologic data were collected. Fifty-six patients with a postoperative infection were compared with 340 patients without infection. Hazard ratios and overall cumulative risk were evaluated. There was no difference in survival, local recurrence or metastasis between patients with or without a postoperative infection. Patients were evenly matched for age at diagnosis, gender, smoking status, and diabetes status. Tumor characteristics did not differ between groups in tumor size, location, depth, grade, margin status, stage, and histologic subtype. There was no difference in utilization of chemotherapy or radiation therapy between groups. From our competing risk model, only positive margin status significantly impacted the risk of local recurrence. An increase in tumor size corresponded to an increased risk of metastasis and death. Postoperative infection neither conferred a protective effect, nor increased the risk of adverse oncologic outcomes after soft tissue sarcoma resection. J. Surg. Oncol. © 2013 Wiley Periodicals, Inc.
    No preview · Article · Apr 2014 · Journal of Surgical Oncology
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    ABSTRACT: Osteosarcoma is the most common primary malignant tumor of bone and accounts for half of all primary skeletal malignancies in children and teenagers. The prognosis for patients who fail or progress on first-line chemotherapy protocols is poor, therefore, additional adjuvant therapeutic strategies are needed. A recent feasibility study has demonstrated that the nitrogen-containing bisphosphonate zoledronic acid (ZOL) can be combined safely with conventional chemotherapy. However, the pharmacodynamics of bisphosphonate therapy is not well characterized. Osteosarcoma is a highly angiogenic tumor. Recent reports of the anti-angiogenic effects of bisphosphonates prompted us to determine whether nitrogen-containing bisphosphonates (ZOL and alendronate) treatment attenuate osteosarcoma growth by inhibition of osteoclast activity, tumor-mediated angiogenesis, or direct inhibitory effects on osteosarcoma. Here, we demonstrate that bisphosphonates directly inhibit VEGFR2 expression in endothelial cells, as well as endothelial cell proliferation and migration. Additionally, bisphosphonates also decrease VEGF-A expression in osteosarcoma (K7M3) cells, resulting in reduced stimulation of endothelial cell migration in co-culture assays. ZOL also decreases VEGFR1 expression in aggressive osteosarcoma cell lines (K7M3, 143B) and induces apoptosis of these cells, but has negligible effects on less aggressive osteosarcoma cell lines (K12 and TE85). In vivo ZOL treatment results in significant reduction in osteosarcoma-initiated angiogenesis and tumor growth in a murine model of osteosarcoma. In conclusion, bisphosphonates have diverse growth inhibitory effects on osteosarcoma through: (1) activation of apoptosis and inhibition of cell proliferation, (2) inhibition of VEGF-A and VEGFR1 expression by tumor cells, (3) inhibition of tumor-induced angiogenesis, and (4) direct inhibitory actions on endothelial cells.
    Full-text · Article · Mar 2014 · Bone
  • Vignesh K Alamanda · Yanna Song · Herbert S Schwartz · Ginger E Holt
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    ABSTRACT: Racial disparities in access and survival have been reported in a variety of cancers. These issues, however, have yet to be explored in detail in patients with soft-tissue sarcomas (STS). The purpose of this paper was to investigate the independent role of race with respect to survival outcomes in STS. A total of 7601 patients were evaluated in this study. A SEER registry query for patients over 20 years old with extremity STS diagnosed between 2004 and 2009 (n=7225) was performed. Survival outcomes were analyzed after patients were stratified by race. Multivariable survival models were used to identify independent predictors of sarcoma-specific death. The Wilcoxon rank-sum test was used to compare continuous variables. Statistical significance was maintained at P<0.05. This study showed that African American patients were more likely to die of their STS. They were younger at presentation (P=0.001), had larger tumors (P<0.001), had less surgery (P=0.002), received radiotherapy less frequently (P=0.024), had higher family income (P<0.001), and were less likely to be married (P<0.001). African American race by itself was not an independent predictor of death. African Americans encounter death due to STS at a much larger proportion and faster rate than their respective white counterparts. African Americans frequently present with a larger size tumor, do not undergo surgical resection, or receive radiation therapy as frequently as compared with their white peers. Barriers to timely and appropriate care should be further investigated in this group of at-risk patients.
    No preview · Article · Jan 2014 · American journal of clinical oncology
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    ABSTRACT: Soft tissue sarcomas (STS) continue to be excised inappropriately without proper preoperative planning. The reasons for this remain elusive. The role of insurance status and patient distance from sarcoma center in influencing such inappropriate excisions were examined in this study. This retrospective review of a single institution prospective database evaluated 400 patients treated for STS of the extremities between January 2000 and December 2008. Two hundred fifty three patients had a primary excision while 147 patients underwent re-excision. Wilcoxon rank sum test and either χ(2) or Fisher's exact were used to compare variables. Multivariable regression analyses were used to take into account potential confounders and identify variables that affected excision status. Tumor size, site, depth, stage, margins, and histology were significantly different between the primary excision and re-excision groups; P < 0.05. Insurance status and patient distance from the treatment center were not statistically different between the two groups. Large and deep tumors and certain histology types predicted appropriate referral. Inappropriate excision of STS is not influenced by patient distance from a sarcoma center or by a patient's insurance status. In this study, tumor size, depth, and certain histology types predicted the appropriate referral of a STS to a sarcoma center. J. Surg. Oncol. © 2013 Wiley Periodicals, Inc.
    No preview · Article · Dec 2013 · Journal of Surgical Oncology
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    ABSTRACT: Background and objectives: Administration of preoperative radiotherapy for extremity soft tissue sarcoma improves local control, while allowing for a more conservative surgical resection. During radiation treatment tumor size typically decreases or remains constant. In a subset of patients, however, a size increase in the tumor occurs. Our goal was to investigate the prognosis of patients who had a size increase of at least 20% over the course of preoperative radiotherapy versus those who did not. Methods: This retrospective study evaluated 70 patients treated for localized primary STS of the extremities between January 2000 and December 2008. Kaplan-Meier curves for disease-specific and metastasis-free survival were calculated for both groups. Results: Sixty-one patients had stable or decrease local tumor size following preoperative radiotherapy and nine patients had an increase of at least 20% in tumor size. There were no statistically significant differences found in disease-specific survival and metastasis-free survival (Gray's test, P = 0.93 and P = 0.68, respectively) among the two groups. Conclusion: Our results indicate that a 20% increase in tumor size following preoperative radiotherapy did not result in a worse outcome for patients when compared to those who had stable or decrease local tumor size following preoperative radiotherapy.
    No preview · Article · Jun 2013 · Journal of Surgical Oncology

Publication Stats

3k Citations
623.03 Total Impact Points


  • 1990-2015
    • Vanderbilt University
      • Department of Orthopaedic Surgery and Rehabilitation
      Нашвилл, Michigan, United States
    • Medical College of Wisconsin
      • Department of Orthopaedic Surgery
      Milwaukee, WI, United States
  • 2012
    • McMaster University
      • Department of Surgery
      Hamilton, Ontario, Canada
    • Institute for Orthopaedic Surgery
      Lima, Ohio, United States
  • 1973-1984
    • Roswell Park Cancer Institute
      • • Department of Experimental Therapeutics
      • • Grace Cancer Drug Center
      Buffalo, New York, United States
  • 1976
    • University of Illinois at Chicago
      Chicago, Illinois, United States
  • 1960-1963
    • Memorial Sloan-Kettering Cancer Center
      New York City, New York, United States
  • 1953
    • University of California, Los Angeles
      • Department of Pharmacology
      Los Angeles, California, United States