M E Wohl

Boston Children's Hospital, Boston, Massachusetts, United States

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Publications (29)141.43 Total impact

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    ABSTRACT: Patients with cystic fibrosis (CF) are known to be at risk for early osteoporosis, and the mechanisms that mediate bone loss are still being delineated. The aim of the present investigation was to investigate if a correlation exists in these patients between skeletal measurements by dual-energy x-ray absorptiometry (DXA) and two anabolic factors, dehydroepiandrosterone (DHEA) and insulin-like growth factor I (IGF-I), and proresorptive factors such as the cytokines interleukin-1beta, tumor necrosis factor alpha, and interleukin-6. We studied 32 outpatients (18 females; mean age: 26.2+/-7.9 years) at a tertiary care medical center. The subjects had venous samples obtained, underwent anthropometric and bone mineral density (BMD) measurements, and completed a health survey. Serum IGF-I concentrations were below the age-adjusted mean in 78% of the participants, and DHEA sulfate (DHEAS) concentrations were low in 72%. Serum concentrations of all cytokines were on the low side of normal; nonetheless, there was a modest inverse correlation between IL-1beta and BMD at all sites. In univariate analyses, IGF-I and DHEAS were significant correlates of BMD or bone mineral content. In final multivariate models controlling for anthropometric and other variables of relevance to bone density, only IGF-I was identified as a significant independent skeletal predictor. While alterations in DHEAS, IGF-I, and specific cytokines may contribute to skeletal deficits in patients with CF, of these factors a low IGF-I concentration appears to be most strongly correlated with BMD. These findings may have therapeutic implications for enhancing bone density in these patients.
    Osteoporosis International 02/2006; 17(5):783-90. DOI:10.1007/s00198-005-0058-x · 4.17 Impact Factor
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    ABSTRACT: Our objective was to describe the respiratory complications, clinical findings, and chest radiographic changes in the first year of life in infected and uninfected children born to HIV-1-infected women. We prospectively followed a cohort of 600 infants born to HIV-1-infected women from birth to 12 months in a multicenter study. Of these, 93 infants (15.5%) were HIV-1-infected, 463 were uninfected, and 44 were of unknown status prior to death or loss to follow-up. The cumulative incidence ( +/- SE) of an initial pneumonia episode at 12 months was 24.1 +/- 4.7% in HIV-1-infected children compared to 1.4 +/- 0.6% in HIV-1-uninfected children (P < 0.001). The rate of Pneumocystis carinii pneumonia (PCP) was 9.5 per 100 child-years. The HIV-1 RNA load was not higher in the group that developed pneumonia in the first year vs. those who did not. Children who developed lower respiratory tract infections or PCP had increased rates of decline of CD4 cell counts during the first 6 months of life. Lower maternal CD4 cell counts were associated with higher rates of pneumonia, and upper and lower respiratory tract infections. The rates of upper respiratory tract infection and bronchiolitis/reactive airway disease in infected children were not significantly different than in uninfected children. At 12 months, significantly more HIV-1-infected than uninfected children had tachypnea and chest radiographs with nodular and reticular densities. There was no relationship between cytomegalovirus infection in the first year of life and radiographic changes or occurrences of pneumonia. In conclusion, despite a low incidence of PCP, rates of pneumonia remain high in HIV-infected children in the first year of life. The incidence of pneumonia in uninfected infants born to HIV-1-infected mothers is low. Chest X-ray abnormalities and tachypnea suggest that subacute disease is present in infected infants. Further follow-up is warranted to determine its nature.
    Pediatric Pulmonology 04/2001; 31(4):267-76. · 2.30 Impact Factor
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    ABSTRACT: The Pediatric Pulmonary and Cardiovascular Complications of Vertically Transmitted HIV (P(2)C(2) HIV) Study is a multicenter study examining pulmonary and cardiac outcomes in offspring of HIV-infected mothers. This portion of the P(2)C(2) study tests the hypothesis that infants exposed to, but uninfected by, maternal HIV have normal maximal expiratory flow at functional residual capacity (V'max,(FRC)). We obtained 500 measurements of V'max,(FRC) by rapid thoracic compression in 285 children ages 6-30 mo in five U.S. centers. The data were compared with those from a healthy cohort of children described elsewhere. V'max,(FRC) rose with height in a linear relationship. The slope of the regression line in the exposed infants did not differ statistically from the slope in the comparison group, but the intercept was about 20% lower (p < 0.001). Height and weight were comparable in the two cohorts, and the differences between intercepts persisted after adjusting for birth weight and gestational age. However, maternal HIV infection cannot be assumed to be the cause as the cohorts may have differed in other variables, such as socioeconomic status and frequency of maternal smoking and drug use. Also, measurements varied substantially within and between our five centers, probably in part because of different racial and ethnic distributions. In summary, maternal HIV infection probably has only a modest effect, if any, on maximal expiratory flow at functional residual capacity in uninfected infants.
    American Journal of Respiratory and Critical Care Medicine 03/2001; 163(4):865-73. DOI:10.1164/ajrccm.163.4.9901040 · 11.99 Impact Factor
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    ABSTRACT: The thoracoabdominal compression technique (TAC) is used to measure expiratory flow in infants. We investigated whether TAC caused a change in total thoracic compliance (Crs), resistance (Rrs), and respiratory system time constant (Trs). We studied 41 infants (mean age, 12.4 mo; SD, 7.5) from five centers studying longitudinal lung and cardiovascular function of infants from HIV-infected mothers. We measured Crs, Rrs, and Trs before and after TAC. Changes in Crs, Rrs, and Trs after TAC were not dependent on the length of time since TAC. Crs and Trs were reduced after TAC, p = 0.013 and p = 0.003, respectively, whereas Rrs did not change. When compared with uninfected infants, HIV-infected infants had a larger post-pre TAC percent decline in Crs (p = 0.003) and a post-pre TAC rise in mean Rrs (p = 0.03). These differences remained significant after adjusting for sex and age. When performing infant pulmonary function testing, TAC itself produces a temporary decrease in Crs and Trs that is more significant in infants at risk for abnormal lung volume or compliance. Therefore, the sequence of performing the infant lung function parameters should be the same each time the testing is repeated with TAC as the last parameter tested at each testing session.
    American Journal of Respiratory and Critical Care Medicine 06/2000; 161(5):1567-71. DOI:10.1164/ajrccm.161.5.9902066 · 11.99 Impact Factor
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    ABSTRACT: Cystic fibrosis (CF) is a complex illness characterized by chronic lung infection leading to deterioration in function and respiratory failure in over 85% of patients. An understanding of the risk factors for that progression and the interaction of these factors with current therapeutic strategies should materially improve the prevention of this progressive lung disease. The Epidemiologic Study of Cystic Fibrosis (ESCF) was therefore designed as a multicenter, longitudinal, observational study to prospectively collect detailed clinical, therapeutic, microbiologic, and lung function data from a large number of CF treatment sites in the U.S. and Canada. The ESCF also serves an important role as a phase-IV study of dornase alfa. To be eligible for enrollment, subjects must have the diagnosis of CF and receive the majority of their care at an ESCF site. In this paper, the authors present the ESCF study design in detail. Further, enrollment data collected at 194 study sites in 18,411 subjects enrolled from December 1, 1993 to December 31, 1995 are presented in summary form. This comprehensive study is unique in the detail of clinical data collected regarding patient monitoring and therapeutic practices in CF care. Two companion articles present data regarding practice patterns in cystic fibrosis care, including data on resource utilization and prescribing practices.
    Pediatric Pulmonology 11/1999; 28(4):231-41. · 2.30 Impact Factor
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    C Johnson, ME Wohl, SM Butler
    Value in Health 05/1999; 2(3):133-133. DOI:10.1016/S1098-3015(11)70835-X · 2.89 Impact Factor
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    ABSTRACT: The purpose of this study was to determine predictors of accelerated deterioration in radiographic manifestations of cystic fibrosis. The incidence and distribution of focally accentuated disease were also studied. From 230 patients, 3038 chest radiographs were scored using the Brasfield system. Scores were plotted against age, and a single age-based severity curve was created. Specific observations (at least one episode in the first 5 years of life of air trapping, linear markings, nodular cystic lesions, or large lesions) were assessed to determine predictors of accelerated decline in scores compared with the aggregate scores plotted in the age-based severity curve. Specific observations were noted as present or absent and graded as to severity. A specific observation was counted as present if seen on at least one occasion. (The number of occasions on which the observation was made did not affect statistical analysis.) We also evaluated the distribution of lung disease by assessing the severity and nature of disease through specific lobar distribution. Males showed a slightly greater rate of radiologic decline. Early development of air trapping or bronchiectasis was associated with an accelerated rate of decline over time. Lobe-dominant disease occurred in one third of all images and in two thirds of the patients. It varied with age in its incidence, location, and etiology. Hyperinflation or bronchiectasis that occurs before age 5 is associated with accelerated radiographic deterioration. The incidence and location of lobe-dominant disease varied with age in these patients.
    American Journal of Roentgenology 12/1998; 171(5):1311-5. DOI:10.2214/ajr.171.5.9798870 · 2.74 Impact Factor
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    ABSTRACT: This study presents a radiography-based database scoring changes over time in a large population of patients with cystic fibrosis. The purpose of this database is to provide comparison for groups of patients undergoing experimental treatment to assess effect of the treatment. The data may also be used to compare individuals with their age-matched cohorts with cystic fibrosis. From 230 patients, 3038 chest radiographs were scored using the Brasfield system. The scores from radiographs from all the patients were individually plotted for age, and a single age-based severity curve was created. The age-based severity curve was compared with similar curves derived from pulmonary function studies of a subset of the same patient population. We found high inter- and intraobserver reliability. The difference between the observers averaged 1.3 Brasfield points, the scale of which ranges up to 25 points. The age-based severity curve was presented as mean Brasfield scores versus age (birth to > 30 years) plotted with 95% confidence limits; the curve was also plotted in percentiles. The rate of decline of this curve was similar to the decline of pulmonary function studies in this patient population. The age-based curve, a structural anatomic parameter, differs from pulmonary function studies, which are functional. Thus the age-based severity curve provides an additional, independent basis for comparison between groups and individuals. It may be used for the initial assessment of lung disease and for gauging and predicting the rate of decline. The curve may be used as a long-range outcome criterion to evaluate new treatments in groups of patients with cystic fibrosis.
    American Journal of Roentgenology 04/1998; 170(4):1067-72. DOI:10.2214/ajr.170.4.9530060 · 2.74 Impact Factor
  • A A Colin, M E Wohl
    Pediatrics in Review 06/1994; 15(5):192-200. · 0.82 Impact Factor
  • A. A. Colin, M. E. B. Wohl
    Pediatrics in Review 05/1994; 15(5):192-200. DOI:10.1542/pir.15-5-192 · 0.82 Impact Factor
  • R Zinman, M E Wohl, R H Ingram
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    ABSTRACT: In spontaneous asthma after a deep inhalation (DI) obstruction occurs in direct proportion to disease severity. Since this has been associated with peripheral inflammation, which is present in cystic fibrosis (CF), we tested whether worsening obstruction after DI also occurs in CF in 12 patients. We assessed volume history effects by comparing isovolumic expiratory flows (Vmax) during forced exhalation begun at the end of tidal inspiration (partial P) with those begun at TLC (maximal M) to obtain M/P. As in asthma there was a correlation between M/P and FEV1 (% predicted; r = 0.64, p less than or equal to 0.03, n = 12). To control for a time dependency effect due to preferential emptying of fast compartments early in both the P and M maneuvers, we compared Vmax obtained from a first partial (P1) with a second (P2) obtained after inspiration to TLC and slow exhalation to the same starting volume as P1 (P2/P1). In contrast to asthma the P2/P1 was greater than the M/P and not related to disease severity. A further index of nonhomogeneous lung emptying was the relationship between M/P and the slope ratio at 70% TLC (r = -0.67, p less than or equal to 0.03). After isoetharine inhalation the M/P decreased (-0.12 +/- 0.12, p less than or equal to 0.01) but no change was apparent in P2/P1, indicating further increases in the degree of nonhomogeneity. We conclude that although volume history effects on M/P are similar in asthma and CF, this is due to a predominance of parenchymal hysteresis in the former and nonhomogeneity in the latter, which worsens with bronchodilator use.
    The American review of respiratory disease 07/1991; 143(6):1257-61. DOI:10.1164/ajrccm/143.6.1257 · 10.19 Impact Factor
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    ABSTRACT: Achondroplasia is a unique model of the effects of skeletal dysplasia and dwarfism on the respiratory system. We measured chest dimensions, spirometry, lung volumes, maximal expiratory flow volume curves, nasal and airways resistance, closing volume, maximal inspiratory/expiratory pressures, and tracheal area by acoustic reflection in 12 healthy subjects with achondroplasia. Anterior-posterior thoracic diameter was mildly reduced in men. Vital capacity for all subjects was 108 percent +/- 18.6 percent (SD) of that predicted for achondroplastic subjects, but was reduced when compared with values for people of average stature that were predicted, based on either sitting height or thoracic height. The reduction was relatively greater in male than in female subjects. The RV/TLC and FRC/TLC ratios were normal. Other measurements were similar to those in average-statured adults. We conclude that achondroplasia results in a reduction in vital capacity out of proportion to what would be expected if these subjects had normal limb size. Although the lungs may be small, they are functionally normal, as are the airways.
    Chest 08/1990; 98(1):145-52. · 7.13 Impact Factor
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    ABSTRACT: As the shape, compliance, and deformability of the rib cage (RC) change during infancy, RC participation in quiet breathing may increase. We used respiratory inductive plethysmography (RIP) to determine the relative contributions of the RC and abdomen (AB) to tidal volume (VT) in 20 studies in 14 healthy infants 1 to 26 months of age during quiet natural sleep. RIP was calibrated with simultaneous flow measurements (anesthesia mask and pneumotachograph) by the least squares method of statistical analysis. We analyzed segments of breathing with and without flow measurement for RIP-derived VT, change in RC volume (Vrc) and AB volume (Vab) with each breath and the RC contribution to tidal breathing (%RC = Vrc/Vrc + Vab). The %RC increased with age: %RC = 1.4 age (months) + 33 (r = 0.69, p less than 0.01). After 9 months of age, %RC resembled that found in quietly sleeping adolescents. Mask placement increased VT in all but one subject (mean increase, 29 +/- 23% of baseline +/- SD; p less than 0.001, paired t test). In infants younger than 10 months of age, mask placement also increased %RC (without mask, 40 +/- 9%; with mask, 46 +/- 10% p less than 0.02). We conclude that by 1 yr of age, the RC contribution to tidal breathing during quiet sleep is similar to that of the adolescent, suggesting that major developmental changes in RC shape, compliance, and deformability take place during infancy.
    The American review of respiratory disease 05/1990; 141(4 Pt 1):922-5. DOI:10.1164/ajrccm/141.4_Pt_1.922 · 10.19 Impact Factor
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    ABSTRACT: We used respiratory inductance plethysmography to record tidal respiration in 27 healthy unsedated infants and children 1 mo to 8 yr of age during sleep. Rib cage and abdominal outputs were present at approximately equal gains and summed to obtain an estimate of volume. Flow-volume curves were generated from the uncalibrated volume signal and its flow derivative. Expiratory time constants (tau) were obtained by visually drawing a line through the linear portion of the expiratory flow-volume relationship. tau increased significantly during the first 10 mo of life. After 10 mo, the estimated rate of increase of tau for older children was less than 5% of the estimated initial rate and not significantly different from zero. Prolongation of tau was paralleled by an increase in expiratory time (Te), and no changes in Te/tau were observed in the first 2 yr of life. These changes in tau likely reflect the increase in lung compliance induced by rapid alveolar growth during infancy. After the first year, expiratory time constants appear to remain relatively constant and may be consistent with balanced changes in compliance and resistance beyond infancy.
    Journal of Applied Physiology 12/1989; 67(5):2112-5. · 3.43 Impact Factor
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    ABSTRACT: Newborn infants, in contrast to adults, dynamically maintain end-expiratory lung volume (EEV) above relaxation volume. The purpose of this study was to determine at what age children develop a breathing strategy that is relaxed, i.e., determined by the mechanical characteristics of the lung and chest wall. Forty studies were performed in 27 healthy infants and children aged 1 mo to 8 yr during natural sleep. Volume changes were recorded with the use of respiratory inductance plethysmography (RIP). The volume signal was differentiated to yield flow. Flow-volume representations were generated for a random sample of the recorded breaths to determine the predominant breathing strategy utilized, i.e., relaxed, interrupted, or indeterminate. The respiratory pattern was predominantly interrupted below 6 mo of age and predominantly relaxed over 1 yr of age. Mixed patterns were observed in children 6-12 mo of age. The number of breaths that could not be classified (indeterminate) decreased with age. Respiratory frequency measured from the sample of breaths decreased with age and was accompanied by an increase in expiratory time. We conclude that a relaxed EEV develops at the end of the first year of life and may be related to changes in the mechanical properties of the chest wall associated with growth as well as changes in respiratory timing.
    Journal of Applied Physiology 12/1989; 67(5):2107-11. · 3.43 Impact Factor
  • F Ratjen, R Zinman, M E Wohl
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    ABSTRACT: Partial expiratory flow-volume (PEFV) curves in infants are generated by applying a compressive pressure over the chest wall with an inflatable jacket. This study addresses two issues: pressure transmission to and across the chest wall and whether flow limitation can be identified. Eleven infants sedated with chloral hydrate were studied. Pressure transmission to the chest wall, measured with neonatal blood pressure cuffs placed on the infant's body surface, was 72 +/- 4% of jacket pressure during compression maneuvers. The pressure transmission to the air spaces, determined by measuring airway pressure during a compression maneuver against an occluded airway, was 56 +/- 6% of jacket pressure. A significant amount of the applied pressure is therefore lost across both the jacket and chest wall. Rapid pressure oscillations (RPO) were superimposed on static jacket pressures while expiratory flow was measured. Absence of associated oscillations of flow measured at the mouth was taken to indicate that flow was independent of driving pressure and therefore limited. Flow limitation was demonstrable with the RPO technique in all infants for jacket pressures greater than 50 cmH2O; however, it was evident at jacket pressures less than 30 cmH2O jacket pressure in four infants with obstructive airway disease. The RPO technique is a useful adjunct to the compression maneuver utilized to generate PEFV curves in infants because it facilitates the recognition of expiratory flow limitation.
    Journal of Applied Physiology 11/1989; 67(4):1662-9. · 3.43 Impact Factor
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    ABSTRACT: Total respiratory system compliance (Crs) at volumes above the tidal volume (VT) was studied by use of the expiratory volume clamping (EVC) technique in 10 healthy sleeping unsedated newborn infants. Flow was measured with a pneumotachograph attached to a face mask and integrated to yield volume. Volume changes were confirmed by respiratory inductance plethysmography. Crs measured by EVC was compared with Crs during tidal breathing determined by the passive flow-volume (PFV) technique. Volume increases of approximately 75% VT were achieved with three to eight inspiratory efforts during expiratory occlusions. Crs above VT was consistently greater than during tidal breathing (P less than 0.0005). This increase in Crs likely reflects recruitment of lung units that are closed or atelectatic in the VT range. Within the VT range, Crs measured by PFV was compared with that obtained by the multiple-occlusion method (MO). PFV yielded greater values of Crs than MO (P less than 0.01). This may be due to braking of expiratory airflow after the release of an occlusion or nonlinearity of Crs. Thus both volume recruitment and airflow retardation may affect the measurement of Crs in unsedated newborn infants.
    Journal of Applied Physiology 10/1989; 67(3):1192-7. · 3.43 Impact Factor
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    ABSTRACT: Chest radiographs were compared for three groups of children 8-9 years old: 23 survivors of bronchopulmonary dysplasia (BPD), 33 survivors of hyaline membrane disease without BPD, and 35 survivors of premature birth without neonatal respiratory problems. Only four children in the second group and three in the third had abnormal lungs. Linear shadows, apparently representing strands of fibrosis or deep pleural fissuring, were seen more frequently (15 of 23) in the BPD group than in the others (P less than .0001). Seventeen children in the BPD group had definite pulmonary abnormalities, none of them severe. The anteroposterior dimension of the chest in survivors of BPD tended to be decreased (P less than .001 vs that of reported control subjects).
    Radiology 07/1989; 171(3):811-4. DOI:10.1148/radiology.171.3.2717757 · 6.21 Impact Factor
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    ABSTRACT: R. Peslin et al. measured thoracic gas volume (TGV) in adults using a new method employing low-frequency ambient pressure changes (APC) (J. Appl. Physiol. 62: 359-363, 1987). We extended that methodology and then tested the hypothesis that this technique was applicable to small mammals. TGV [at functional residual capacity (FRC)] by APC and by conventional Boyle's law was compared in 12 rabbits. The rabbits were anesthetized, tracheostomized, intubated, and placed in a pressure plethysmograph. Although in the method of Peslin et al. box pressure was oscillated at a single frequency, in our extension box pressure was oscillated simultaneously at two frequencies (0.1 and 0.2 Hz). Flow at the airway opening consisted of rapid events due to spontaneous breathing, superposed on slower events due to the alveolar gas compression. The slower events were analyzed to yield alveolar gas compliance and, by Boyle's law, FRC. FRC by APC was highly correlated to FRC by conventional plethysmography (r = 0.85). Compared with the methodology of Peslin et al., our extension relaxes a key limitation and yields systematically higher estimates of FRC. We conclude that this method is applicable to small mammals, despite an inherently more compliant chest wall, and that the methodological extension improves the estimate of FRC.
    Journal of Applied Physiology 10/1988; 65(3):1444-8. · 3.43 Impact Factor
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    ABSTRACT: We examined airway vs. lung parenchymal growth, as inferred from maximal expiratory flows (MEF) and lung volumes (V), respectively, to determine whether the interindividual variability of airway size (inferred from MEF) changes during lung growth and whether a young child with large (or small) airways for his parenchymal size (inferred from V) maintains relatively large (or small) airways for his lung size as he grows to adulthood. Serial measurements of MEF and V were obtained from a cohort of healthy 6- to 27-yr-old males (n = 26) and females (n = 21) over a period of 18 yr. Data were analyzed using logarithmic transformation of the power law equation, MEF = aVb, to fit a regression line to each subject's data points. These growth trajectories were satisfactorily modeled as parallel lines with 20-30% variability of their y-intercepts, indicating that substantial intersubject variability of MEF relative to V is present in early childhood and remains constant during growth. The results further indicate that MEF does track V during lung growth. We conclude that dysanapsis originates in early childhood.
    Journal of Applied Physiology 09/1988; 65(2):822-8. · 3.43 Impact Factor

Publication Stats

638 Citations
141.43 Total Impact Points


  • 1989–2006
    • Boston Children's Hospital
      Boston, Massachusetts, United States
  • 2001
    • Mount Sinai School of Medicine
      • Department of Pediatrics
      Manhattan, NY, United States
  • 2000
    • Children's Hospital Los Angeles
      Los Angeles, California, United States
  • 1988–1998
    • Harvard Medical School
      • • Department of Radiology
      • • Department of Pediatrics
      Boston, Massachusetts, United States
    • St. Michael's Hospital
      Toronto, Ontario, Canada
    • Wolfson Childrens Hospital
      Jacksonville, Florida, United States