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Dive into the research topics where Robert H. Cleveland is active.

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Featured researches published by Robert H. Cleveland.


Proceedings of the National Academy of Sciences of the United States of America | 2012

Clinical trial of a farnesyltransferase inhibitor in children with Hutchinson–Gilford progeria syndrome

Leslie B. Gordon; Monica E. Kleinman; David T. Miller; Donna Neuberg; Anita Giobbie-Hurder; Marie Gerhard-Herman; Leslie B. Smoot; Catherine M. Gordon; Robert H. Cleveland; Brian D. Snyder; Brian Fligor; W. Robert Bishop; Paul Statkevich; Amy Regen; Andrew L. Sonis; Susan Riley; Christine Ploski; Annette Correia; Nicolle Quinn; Nicole J. Ullrich; Ara Nazarian; Marilyn G. Liang; Susanna Y. Huh; Armin Schwartzman; Mark W. Kieran

Hutchinson–Gilford progeria syndrome (HGPS) is an extremely rare, fatal, segmental premature aging syndrome caused by a mutation in LMNA that produces the farnesylated aberrant lamin A protein, progerin. This multisystem disorder causes failure to thrive and accelerated atherosclerosis leading to early death. Farnesyltransferase inhibitors have ameliorated disease phenotypes in preclinical studies. Twenty-five patients with HGPS received the farnesyltransferase inhibitor lonafarnib for a minimum of 2 y. Primary outcome success was predefined as a 50% increase over pretherapy in estimated annual rate of weight gain, or change from pretherapy weight loss to statistically significant on-study weight gain. Nine patients experienced a ≥50% increase, six experienced a ≥50% decrease, and 10 remained stable with respect to rate of weight gain. Secondary outcomes included decreases in arterial pulse wave velocity and carotid artery echodensity and increases in skeletal rigidity and sensorineural hearing within patient subgroups. All patients improved in one or more of these outcomes. Results from this clinical treatment trial for children with HGPS provide preliminary evidence that lonafarnib may improve vascular stiffness, bone structure, and audiological status.


Radiology | 2008

Multidetector CT Evaluation of Congenital Lung Anomalies

Edward Y. Lee; Phillip M. Boiselle; Robert H. Cleveland

Congenital lung anomalies vary widely in their clinical manifestation and imaging appearance. Although radiographs play a role in the incidental detection and initial imaging evaluation in patients with clinical suspicion of congenital lung anomalies, cross-sectional imaging such as computer tomography (CT) is frequently required for confirmation of diagnosis, further characterization, and preoperative evaluation in the case of surgical lesions. Recently, with the development and widespread availability of multidetector CT scanners, CT has assumed a greater role in the noninvasive evaluation of congenital lung anomalies. The combination of fast speed, high spatial resolution, and enhanced quality of multiplanar reformation and three-dimensional reconstructions makes multidetector CT an ideal noninvasive method for evaluating congenital lung anomalies. In this article, the authors review the multidetector CT technique for evaluation of congenital lung anomalies. Important clinical aspects, characteristic imaging features, and key points that allow differentiation among various anomalies are highlighted for a variety of common and uncommon conditions.


Anesthesiology | 1992

Radiologic Localization of the Laryngeal Mask Airway in Children

Nishan G. Goudsouzian; William T. Denman; Robert H. Cleveland; George D. Shorten

In the absence of data on the anatomic localization of the cuff of the laryngeal mask airway (LMA) in children, radiologic images were obtained from 50 infants and children (aged 1 month to 15 yr) undergoing diagnostic radiologic procedures during halothane and N2O:O2 anesthesia. In 46 patients, the cuff of the LMA was in the pharynx and covered the laryngeal opening. The upper (proximal) section was adjacent to the base of the tongue at the level of C1 or C2 vertebrae pushing the tongue forward and its lower (distal) end was in the inferior recesses of the hypopharynx at the levels of C4 to T1 vertebrae. The cuff of LMA at this position between the base of the tongue above the epiglottis and below the laryngeal opening, covered the laryngeal aperture, forming a low pressure seal at the entrance of the larynx. In 37 of these 46 patients, a posterior deflection of the epiglottis was noted (< 45 degrees), and in only 9, the epiglottis was in the anatomic position. In four patients, the cuff of the LMA was located in the oropharynx. No correlation was found between the size of the LMA and the position of the epiglottis with respect to end-tidal CO2, respiratory rate, or the leak pressures. The size of the LMA, its anatomic location, and the position of the epiglottis had no significant effect on the respiratory parameters of spontaneously breathing children.


European Respiratory Journal | 2008

Necrotising pneumonia is an increasingly detected complication of pneumonia in children

Gregory S. Sawicki; Frank Leigh Lu; Clarissa Valim; Robert H. Cleveland; Andrew A. Colin

Necrotising pneumonia (NP) is a severe complication of community-acquired pneumonia characterised by liquefaction and cavitation of lung tissue. The present study describes the epidemiology, aetiology, management and outcomes of children hospitalised with NP over a 15-yr period. A retrospective observational study of NP cases was conducted from January 1990 to February 2005 analysing clinical presentation, laboratory data, hospital course and long-term follow-up. A total of 80 NP cases were identified, with the number of detected cases increasing from 12, in the period 1993–1996, to 40 in the period 2001–2004. In total, 69 (86%) cases had pleural effusion with a low pH (mean 7.08) and 38 (48%) patients had positive cultures, with Streptococcus pneumoniae as the predominant organism. Recently, other organisms, most notably methicillin-resistant Staphylococcus aureus, emerged. Patients had prolonged hospitalisations (median 12 days). A total of 69 patients required pleural interventions and those receiving chest drainage alone had similar outcomes to those managed surgically. All patients had full clinical resolution within 2 months of presentation. Necrotising pneumonia has increasingly been identified as a complication of paediatric pneumonia. Streptococcus pneumoniae remains the predominant organism, but since 2002, different bacteria have been isolated and the age range of cases has broadened. Despite the serious morbidity, massive parenchymal damage and prolonged hospitalisations, long-term outcome following necrotising pneumonia is excellent.


Annals of Emergency Medicine | 1986

Correlation of pulmonary signs and symptoms with chest radiographs in the pediatric age group

D Demetrios Zukin; Jerome R. Hoffman; Robert H. Cleveland; David C. Kushner; Thomas E. Herman

One hundred twenty-five pediatric emergency department patients were studied prospectively to determine whether any findings on the physical examination were predictive of abnormalities seen on chest radiograph. We attempted to find possible correlations between such clinical examination findings, recorded prior to radiographic examination, and three subgroups of radiographic findings: pneumonia, any major radiographic abnormality, and any radiographic abnormality whatsoever. The best screen for pneumonia was presence of fever (temperature greater than two standard deviations above age-related norms), with a sensitivity of 94% and a negative predictive value of 97%. The sign with highest positive and negative predictive value for the presence of any radiographic abnormalities was tachypnea. A subgroup with either normal breath sounds, or findings limited to wheezing, prolonged expiration, cough and/or rhonchi on chest examination proved to be at low risk for any major chest radiographic abnormality. Patients with other chest examination findings comprised a high-risk group with a 34% risk of a major radiographic abnormality, as compared to a 7% incidence in the low-risk group. Thus, absence of fever suggests absence of pneumonia, while chest examination findings other than wheezing, cough, prolonged expiration, or rhonchi significantly increase the likelihood of pneumonia in this population. Physical examination findings can help the clinician determine the need for chest radiography in the pediatric emergency patient.


Journal of Clinical Epidemiology | 1996

The pediatric pulmonary and cardiovascular complications of vertically transmitted human immunodeficiency virus (P2C2 HIV) infection study: Design and methods

Meyer Kattan; Hannah Peavy; Anthony Kalica; Carol Kasten-Sportes; Elaine Sloand; George Sopko; Carol Vreim; Constance Weinstein; Margaret Wu; Robert Mellins; William T. Shearer; Stuart L. Abramson; Nancy A. Ayres; Carol J. Baker; J. Timothy Bricker; Gail J. Demmler; Marilyn Doyle; Maynard Dyson; Janet A. Englund; Nancy Eriksen; Arthur Garson; Bernard Gonik; Hunter Hammill; Thomas N. Hansen; I. Celine Hanson; Peter Hiatt; Keith Hoots; Robert Jacobson; Debra L. Kearney; Mark W. Kline

The P2C2 HIV Study is a prospective natural history study initiated by the National Heart, Lung, and Blood Institute in order to describe the types and incidence of cardiovascular and pulmonary disorders that occur in children with vertically transmitted HIV infection (i.e., transmitted from mother to child in utero or perinatally). This article describes the study design and methods. Patients were recruited from five clinical centers in the United States. The cohort is composed of 205 infants and children enrolled after 28 days of age (Group I) and 612 fetuses and infants of HIV-infected mothers, enrolled prenatally (73%) or postnatally at age < 28 days (Group II). The maternal-to-infant transmission rate in Group II was 17%. The HIV-negative infants in Group II (Group IIb) serves as a control group for the HIV-infected children (Group IIa). The cohort is followed at specified intervals for clinical examination, cardiac, pulmonary, immunologic, and infectious studies and for intercurrent illnesses. In Group IIa, the cumulative loss-to-follow-up rate at 3 years was 10.5%, and the 3-year cumulative mortality rate was 24.9%. The findings will be relevant to clinical and epidemiologic aspects of HIV infection in children.


Pediatrics | 2009

Clinical predictors of pneumonia among children with wheezing.

Bonnie L. Mathews; Sonal Shah; Robert H. Cleveland; Edward Y. Lee; Richard G. Bachur; Mark I. Neuman

OBJECTIVE: The goal was to identify factors associated with radiographically confirmed pneumonia among children with wheezing in the emergency department (ED) setting. METHODS: A prospective cohort study was performed with children ≤21 years of age who were evaluated in the ED, were found to have wheezing on examination, and had chest radiography performed because of possible pneumonia. Historical features and examination findings were collected by treating physicians before knowledge of the chest radiograph results. Chest radiographs were read independently by 2 blinded radiologists. RESULTS: A total of 526 patients met the inclusion criteria; the median age was 1.9 years (interquartile range: 0.7–4.5 years), and 36% were hospitalized. A history of wheezing was present for 247 patients (47%). Twenty-six patients (4.9% [95% confidence interval [CI]: 3.3–7.3]) had radiographic pneumonia. History of fever at home (positive likelihood ratio [LR]: 1.39 [95% CI: 1.13–1.70]), history of abdominal pain (positive LR: 2.85 [95% CI: 1.08–7.54]), triage temperature of ≥38°C (positive LR: 2.03 [95% CI: 1.34–3.07]), maximal temperature in the ED of ≥38°C (positive LR: 1.92 [95% CI: 1.48–2.49]), and triage oxygen saturation of <92% (positive LR: 3.06 [95% CI: 1.15–8.16]) were associated with increased risk of pneumonia. Among afebrile children (temperature of <38°C) with wheezing, the rate of pneumonia was very low (2.2% [95% CI: 1.0–4.7]). CONCLUSIONS: Radiographic pneumonia among children with wheezing is uncommon. Historical and clinical factors may be used to determine the need for chest radiography for wheezing children. The routine use of chest radiography for children with wheezing but without fever should be discouraged.


Pediatric Radiology | 1995

A radiologic update on medical diseases of the newborn chest.

Robert H. Cleveland

This paper reviews the common spectrum of medical diseases of the neonatal chest. Emphasis is on radiographic changes that have been produced by the introduction of new therapeutic maneuvers, particularly the use of artificial surfactant in treating hyaline membrane disease and the survival of profoundly premature newborns (less than 650 g). A discussion of meconium aspiration syndrome, neonatal pneumonia, transient tachypnea of the newborn, congenital lymphangiectasia, and congenital heart disease is also included. The effects on the neonatal chest radiograph of extracorporeal membrane oxygenation and high-frequency ventilation are also mentioned.


Journal of Bone and Mineral Research | 2011

Hutchinson-gilford progeria is a skeletal dysplasia

Catherine M. Gordon; Leslie B. Gordon; Brian D. Snyder; Ara Nazarian; Nicolle Quinn; Susanna Y. Huh; Anita Giobbie-Hurder; Donna Neuberg; Robert H. Cleveland; Monica E. Kleinman; David T. Miller; Mark W. Kieran

Hutchinson‐Gilford progeria syndrome (HGPS) is a rare segmental premature aging disorder that affects bone and body composition, among other tissues. We sought to determine whether bone density and structural geometry are altered in children with HGPS and whether relationships exist among these parameters and measures of skeletal anthropometry, body composition, and nutrition. We prospectively enrolled 26 children with HGPS (ages 3.1 to 16.2 years). Outcomes included anthropometric data; bone age; areal bone mineral density (aBMD) and body composition by dual‐energy X‐ray absorptiometry (DXA); volumetric bone mineral density (vBMD), strength‐strain index (SSI), and bone structural rigidity calculated from radial transaxial peripheral quantitative computed tomographic (pQCT) images; serum bone biomarkers and hormonal measures; and nutrition assessments. Children with HGPS had low axial aBMD Z‐scores by DXA, which improved after adjustment for height age, whereas differences in radial vBMD by pQCT were less striking. However, pQCT revealed distinct abnormalities in both novel measures of bone structural geometry and skeletal strength at the radius compared with healthy controls. Dietary intake was adequate, confirming that HGPS does not represent a model of malnutrition‐induced bone loss. Taken together, these findings suggest that the phenotype of HGPS represents a unique skeletal dysplasia.


Circulation | 2016

Clinical Trial of the Protein Farnesylation Inhibitors Lonafarnib, Pravastatin, and Zoledronic Acid in Children With Hutchinson-Gilford Progeria Syndrome.

Leslie B. Gordon; Monica E. Kleinman; Joe Massaro; Ralph B. D’Agostino; Heather Shappell; Marie Gerhard-Herman; Leslie B. Smoot; Catherine M. Gordon; Robert H. Cleveland; Ara Nazarian; Brian D. Snyder; Nicole J. Ullrich; V. Michelle Silvera; Marilyn G. Liang; Nicolle Quinn; David T. Miller; Susanna Y. Huh; Anne A. Dowton; Kelly Littlefield; Maya Mundkur Greer; Mark W. Kieran

Background: Hutchinson-Gilford progeria syndrome is an extremely rare, fatal, segmental premature aging syndrome caused by a mutation in LMNA yielding the farnesylated aberrant protein progerin. Without progerin-specific treatment, death occurs at an average age of 14.6 years from an accelerated atherosclerosis. A previous single-arm clinical trial demonstrated that the protein farnesyltransferase inhibitor lonafarnib ameliorates some aspects of cardiovascular and bone disease. This present trial sought to further improve disease by additionally inhibiting progerin prenylation. Methods: Thirty-seven participants with Hutchinson-Gilford progeria syndrome received pravastatin, zoledronic acid, and lonafarnib. This combination therapy was evaluated, in addition to descriptive comparisons with the prior lonafarnib monotherapy trial. Results: No participants withdrew because of side effects. Primary outcome success was predefined by improved per-patient rate of weight gain or carotid artery echodensity; 71.0% of participants succeeded (P<0.0001). Key cardiovascular and skeletal secondary variables were predefined. Secondary improvements included increased areal (P=0.001) and volumetric (P<0.001–0.006) bone mineral density and 1.5- to 1.8-fold increases in radial bone structure (P<0.001). Median carotid artery wall echodensity and carotid-femoral pulse wave velocity demonstrated no significant changes. Percentages of participants with carotid (5% to 50%; P=0.001) and femoral (0% to 12%; P=0.13) artery plaques and extraskeletal calcifications (34.4% to 65.6%; P=0.006) increased. Other than increased bone mineral density, no improvement rates exceeded those of the prior lonafarnib monotherapy treatment trial. Conclusions: Comparisons with lonafarnib monotherapy treatment reveal additional bone mineral density benefit but likely no added cardiovascular benefit with the addition of pravastatin and zoledronic acid. Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifiers: NCT00879034 and NCT00916747.

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David Zurakowski

Boston Children's Hospital

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Edward Y. Lee

Boston Children's Hospital

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Vicente Gilsanz

University of Southern California

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Catherine M. Gordon

Cincinnati Children's Hospital Medical Center

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