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Biomedical subjects

John Hayes

Publications and source records attributed to John Hayes.

At least 19 recordsLinked to original sources

Cecostomy in children with defecation disorders.

Administration of antegrade enemas through a cecostomy is a therapeutic option for children with severe defecation disorders. The purpose of this study is to report our 4-year experience with the cecostomy procedure in 31 children with functional constipation (n = 9), Hirschsprung's disease (n = 2), imperforate anus (n = 5), spinal abnormalities (n = 8), and imperforate anus in combination with tethered spinal cord (n = 7). Data regarding complications, antegrade enemas used, symptoms, and quality of life were retrospectively obtained. Placement of cecostomy tubes was successful in 30 of 31 patients. Soiling episodes decreased significantly in children with functional constipation (P = 0.01), imperforate anus (P < 0.01), and spinal abnormalities (P = 0.04). Quality of life improved in patients with functional constipation and imperforate anus. No difference in complications was found between percutaneous and surgical placement. Use of antegrade enemas via cecostomy improved symptoms and quality of life in children with a variety of defecation disorders.

Adolescent↗

An immunohistochemical algorithm to facilitate diagnosis and subtyping of rhabdomyosarcoma: the Children's Oncology Group experience.

Immunohistochemistry remains the current ancillary method of choice in the pathologic evaluation of small blue round-cell tumors. In at least 20% of cases of rhabdomyosarcoma (RMS), it is considered an essential factor in the final and/or differential diagnosis of the malignancy. Newer immunostains (antimyogenin, MyoD1) generated against intranuclear myogenic transcription factors offer pathologists the best hope for improving the sensitivity and specificity of RMS diagnosis. A large series of RMS (956) were studied consecutively from the intergroup rhabdomyosarcoma study and children's oncology group files, along with multiple other malignant, benign or reactive lesions. A panel of antibodies to muscle-related antigens (myogenin, MyoD1, desmin, muscle-specific actin) was studied using formalin-fixed, paraffin-embedded tissue, an avidin-biotin/peroxidase complex immunohistochemical technique, antigen retrieval technique as appropriate, and automated immunostaining. Myogenin and MyoD1 were equally sensitive (positive for 97% of RMS cases), with both also showing similar specificity (90% vs. 91% of cases) for the diagnosis of RMS. Myogenin and MyoD1 staining were sometimes intact in areas of coagulative tumor necrosis, but negated by B5 fixation. Isolated, rare benign myogenin-positive nuclei were seen infrequently in reactive lymph nodes. Specifically, both myogenin and MyoD1 had significantly greater extent of expression for alveolar RMS (ARMS) than embryonal RMS (ERMS) (both with P < 0.001). Similarly, both myogenin (P = 0.001) and MyoD1 (P < 0.001) had significantly higher expression for ARMS than RMS, not otherwise specified (NOS). They were never expressed in undifferentiated sarcomas; however, reactive or regenerative myocytes did show expression. Immunostains against intranuclear myogenic transcription factors are, at present, the best available markers for confirming the diagnosis of RMS. Their differential expression in reactive myogenic lesions, variability in ARMS versus ERMS, and absence in undifferentiated sarcomas suggest new biologic questions to be explored in future studies.

Algorithms↗

Hyperglycemia is a marker for poor outcome in the postoperative pediatric cardiac patient.

OBJECTIVE: Hyperglycemia in critical care populations has been shown to be a risk factor for increased morbidity and mortality. Minimal data exist in postoperative pediatric cardiac patients. The goal of this study was to determine whether hyperglycemia in the postoperative period was associated with increased morbidity or mortality. DESIGN: Retrospective chart review. SETTING: Tertiary care, free-standing pediatric medical center with a dedicated cardiac intensive care unit. PATIENTS: We included 184 patients <1 yr of age who underwent cardiac surgery requiring cardiopulmonary bypass from October 2002 to August 2004. Patients with a weight <2 kg, a preoperative diagnosis of diabetes, preoperative extracorporeal membrane oxygenation support, solid organ transplant recipients, and preoperative renal or liver insufficiency were excluded. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Age was 4.3 +/- 3.2 months and weight was 4.9 +/- 1.7 kg at surgery. Duration of hyperglycemia was significantly longer in patients with renal insufficiency (p = .029), liver insufficiency (p = .006), infection (p < .002), central nervous system event (p = .038), extracorporeal membrane oxygenation use (p < .001), and death (p < .002). Duration of hyperglycemia was also significantly associated with increased intensive care (p < .001) and hospital (p < .001) stay and longer ventilator use (p < .001). Peak glucose levels were significantly different in patients with renal insufficiency (p < .001), infection (p = .002), central nervous system event (p = .01), and mortality (p < .001). CONCLUSIONS: Hyperglycemia in the postoperative period was associated with increased morbidity and mortality in postoperative pediatric cardiac patient. Strict glycemic control may improve outcomes in this patient population.

Cardiac Surgical Procedures↗

Analysis of a micropolarizer array-based simultaneous phase-shifting interferometer.

Recent technological innovations have enabled the development of a new class of dynamic (vibration-insensitive) interferometer based on a CCD pixel-level phase-shifting approach. We present theoretical and experimental results for an interferometer based on this pixelated phase-shifting technique. Analyses of component errors and instrument functionality are presented. We show that the majority of error sources cause relatively small magnitude peak-to-valley errors in measurement of the order of 0.002-0.005lambda. These errors are largely mitigated by high-rate data acquisition and consequent data averaging.

Journal Article↗

Essential role for survivin in early brain development.

Apoptosis is an essential process during normal neuronal development. Approximately one-half of the neurons produced during neurogenesis die before completion of CNS maturation. To characterize the role of the inhibitor of apoptosis gene, survivin, during neurogenesis, we used the Cre-loxP-system to generate mice lacking survivin in neuronal precursor cells. Conditional deletion of survivin starting at embryonic day 10.5 leads to massive apoptosis of neuronal precursor cells in the CNS. Conditional mutants were born at the expected Mendelian ratios; however, these died shortly after birth from respiratory insufficiency, without primary cardiopulmonary pathology. Newborn conditional mutants showed a marked reduction in the size of the brain associated with severe, mutifocal apoptosis in the cerebrum, cerebellum, brainstem, spinal cord, and retina. Caspase-3 and caspase-9 activities in the mutant brains were significantly elevated, whereas bax expression was unchanged from controls. These results show that survivin is critically required for the survival of developing CNS neurons, and may impact on our understanding of neural repair, neural development, and neurodegenerative diseases. Our study is the first to solidify a role for survivin as an antiapoptotic protein during normal neuronal development in vivo.

Animals↗

Visual effects of the luminance surrounding a computer display.

The luminance surrounding a computer display can potentially reduce visibility of the display (disability glare), result in sensations of discomfort (discomfort glare) and result in transient adaptation effects from fixating back and forth between the two luminance levels. The study objective was to measure the effects of surround luminance levels upon these functions in younger and older adults to determine recommended surround luminance levels. The younger age group comprised 20 subjects (mean age 27.9 years, range 23 - 39) and the older group 17 subjects (mean age 55.5 years, range 47 - 63). The central task was presented with luminance of 91 cd/M(2), tested surround luminance levels were 1.4, 2.4, 8.9, 25.5, 50, 91, 175, 317, and 600 cd/M(2). Disability glare was tested with low contrast (20%) visual acuity charts, transient adaptation was tested with a task that required regular fixation between the two luminance levels, discomfort was measured with a questionnaire after reading stories with different surround luminance levels, and preferred luminance was measured by method of adjustment. The surround luminance significantly affected transient adaptation (p < 0.0001), optimal performance occurred at 50 cd/M(2) and above for the young group and at 91 cd/M(2) and above for the older group. Neither low contrast acuity (disability glare) nor symptoms when reading were significantly affected by surround luminance. There was wide variation in preferred surround luminance; however, average preferred surround luminance was 86.9 cd/M(2) for the young group and 62.2 cd/M(2) for the older group, slightly below the central luminance of 91 cd/M(2). The effects of the surround luminance within the tested range are not large; however, the data show that the lowest surround luminance levels should be avoided and that surround luminance levels at or slightly below that of the central task are preferred.

Adaptation, Physiological↗

Cross-reactivity and conformational multiplicity of an anti-polycyclic aromatic hydrocarbon mAb.

Cross-reactivity and multispecific functionality of antibodies play a central role in the immune system. The Ab's promiscuity is attributed to structural flexibility and conformational multiplicity of its binding sites governed by the rearrangement of hydrogen bonding centers. However, antibodies whose recognition and binding rely on less directional hydrophobic interactions might follow different interaction pathways. We investigated interaction of anti-polycyclic aromatic hydrocarbon mAb with two biologically important cross-reactants, pyrene and benzo(a)pyrene. Complex formation was characterized by means of low-temperature laser-induced fluorescence spectroscopy in both low- and high-resolution fluorescence line-narrowing (FLN) modes. It is shown that the FLN spectroscopy can identify various haptens cross-reacted with an Ab, as well as simultaneously differentiate between free and immunocomplexed haptens. In addition, our results suggest an interesting case of an Ab binding a particular cross-reactant by adopting two distinct conformations of its binding sites. The existence of the multiple conformations for anti-polycyclic aromatic hydrocarbon mAb that are trapped at low temperature can be rationalized through the existing models for Ab binding. Finally, as revealed by FLN spectra of immunocomplexed chromophores, pi-pi interactions, rather than hydrogen bonding, play the central role in complex formation.

Antibodies, Monoclonal↗

Improved interstage mortality with the modified Norwood procedure: a meta-analysis.

BACKGROUND: Modification of the Norwood procedure has been reported to improve immediate postoperative mortality compared with the classic Norwood. Interstage mortality has not been shown to be improved with the modified Norwood probably because of the small number of patients from each institution. The goal of this study was to determine if meta-analysis would provide sufficient data to prove statistical difference in interstage mortality for the modified Norwood procedure. METHODS: PubMed was searched using six different terms individually for articles from January 2003 to October 2004. Manuscripts that compared the classic to modified Norwood were reviewed. Mantel-Haenszel analysis was used to evaluate the relationship between treatment method and mortality stratified across hospitals. The Breslow-Day procedure tested homogeneity of odds ratio across hospitals. Separate analyses were performed for inpatient and interstage periods. RESULTS: A total of 4,545 citations was screened. Five manuscripts met the criteria. Seventy-two patients undergoing classic Norwood and 84 patients undergoing modified Norwood survived to initial hospital discharge. The Breslow-Day statistic supported homogeneity of odds ratios for survival across hospitals (chi2 = 2.09, df = 4, p = 0.72). Odds of interstage death was 11.6 times greater (2.2 to 62.1, 95% CI) for the classic Norwood compared with the modified Norwood procedure. This difference was statistically significant by the Mantel-Haenszel chi2 (11.0, p = 0.001). The Breslow-Day statistic supported homogeneity of the odds ratios across hospitals (chi2 = 3.1, df = 4, p = 0.53). CONCLUSIONS: The modified Norwood procedure has a significantly lower interstage mortality compared with the classic Norwood procedure. A large randomized study is needed to determine whether these results remain consistent.

Cardiac Surgical Procedures↗

The risk of child abuse in infants and toddlers with lower extremity injuries.

PURPOSE: The aim of this study was to assess the risk of child abuse in children younger than 18 months admitted to a pediatric trauma service with lower extremity injuries. METHODS: An Institutional Review Board-approved retrospective case series of children admitted to a regional pediatric trauma center with lower extremity injuries from 1998 to 2002 (n = 5497) was performed. Factors analyzed included age, injuries, and injury mechanism. RESULTS: Among 5497 trauma patients, the incidence of abuse was 104 (2%) of 4942 children 18 months or older and 175(32%) of 555 children younger than 18 months (odds ratio [OR], 21.4 +/- 2.9, P < .001). There were 1252 (23%) patients with lower extremity injuries in the entire sample, and 66 of these were younger than 18 months. In the extremity trauma group, for patients 18 months or older, 16 (1%) of 1186 were abused compared with 44 (67%) of 66 patients younger than 18 months (OR, 146 +/- 53, P < .001). Among all trauma patients younger than 18 months, 41 of 55 lower extremity fractures were linked to abuse, whereas 134 of 500 other injuries were caused by abuse (OR, 8.0 +/- 2.6, P < .001). Among the 41 abuse-related fractures, femur fracture was the most common (22), followed by tibia fracture (14). CONCLUSIONS: Among children 18 months or older, abuse is an uncommon cause of lower extremity trauma. In children younger than 18 months, lower extremity injuries, particularly fractures, are highly associated with child abuse. Clinicians must thoroughly investigate lower extremity injuries in this age group.

Child Abuse↗

Testing the association between gastroesophageal reflux and apnea in infants.

BACKGROUND: There is controversy regarding the association between gastroesophageal reflux and apnea. The controversy is further confused by the variety of ways reflux is detected, the varying methods of data analysis and the heterogeneity of subjects studied. OBJECTIVES: To determine if apnea is associated with reflux and to determine whether the association differs with acid or non acid reflux. METHODS: We prospectively evaluated infants with apparent life-threatening events or apnea by simultaneous pneumography, esophageal pH and multichannel intraluminal impedance monitoring. Apneic events and reflux frequency, duration, acidity and height were recorded. Apneic events were considered to be temporally linked to gastroesophageal reflux when they occurred during a gastroesophageal reflux episode or within 5 minutes after clearance of the refluxate. Data described with frequency tables, scatterplots and time series graphs were analyzed by regression analysis and chi testing. RESULTS: Twenty-five infants (10 males) aged 1 to 19 months were studied for up to 24 hours. Of 527 total apneic episodes, only 80 (15.2%) were temporally linked with gastroesophageal reflux: 37 (7.0%) with acid reflux and 43 (8.2%) with non-acid reflux. Scatterplots revealed no significant correlation between apnea and frequency or duration of reflux episodes. Individual chi analyses within subjects found limited associations between reflux and apnea. Regression analyses showed a significant association between apnea and reflux in 4 of 25 subjects. CONCLUSIONS: We found little evidence for an association between apnea and total reflux, acid reflux or non-acid reflux. There was no difference between acid gastroesophageal reflux and non-acid gastroesophageal reflux in the frequency association with apnea. Either a chi statistic for each subject or R value computed from a lagged regression model for each subject can be used as an index of association in patient evaluation.

Apnea↗

Altered bleomycin-induced lung fibrosis in osteopontin-deficient mice.

Osteopontin is a multifunctional matricellular protein abundantly expressed during inflammation and repair. Osteopontin deficiency is associated with abnormal wound repair characterized by aberrant collagen fibrillogenesis in the heart and skin. Recent gene microarray studies found that osteopontin is abundantly expressed in both human and mouse lung fibrosis. Macrophages and T cells are known to be major sources of osteopontin. During lung fibrosis, however, osteopontin expression continues to increase when inflammation has receded, suggesting alternative sources of ostepontin during this response. In this study, we demonstrate immunoreactivity for osteopontin in lung epithelial and inflammatory cells in human usual interstitial pneumonitis and murine bleomycin-induced lung fibrosis. After treatment with bleomycin, osteopontin-null mice develop lung fibrosis characterized by dilated distal air spaces and reduced type I collagen expression compared with wild-type controls. There is also a significant decrease in levels of active transforming growth factor-beta(1) and matrix metalloproteinase-2 in osteopontin null mice. Type III collagen expression and total collagenase activity are similar in both groups. These results demonstrate that osteopontin expression is associated with important fibrogenic signals in the lung and that the epithelium may be an important source of osteopontin during lung fibrosis.

Animals↗

Estimation of pupil size by digital photography.

PURPOSE: To evaluate a digital photography method of pupil size estimation over a broad range of illumination conditions and to compare this method with common clinical techniques. SETTING: College of Optometry, Ohio State University, Columbus, Ohio, USA. METHODS: Two examiners measured the pupil diameter in 45 right eyes at 3 illumination levels: <0.63 lux (dark), 5 lux (dim), and 1000 lux (bright). Estimation by infrared video recording, the reference standard, was compared with measurements by digital photography, ruler, semicircular templates, and the Colvard pupillometer. Masked graders measured pupil size from infrared video recordings and digital photographs. RESULTS: The repeatability of the measurement method determined by the mean intraclass correlation coefficients was highest for video recording across conditions (0.86-0.97), followed by digital photography (0.76-0.94), Colvard pupillometry (0.63-0.82), ruler (0.71-0.85), and templates (0.70-0.83). An analysis of variance showed a significant difference in pupil size by method (P<.001). All methods except digital photography estimated smaller pupil sizes under dark and dim illumination than infrared video measurements (all P<.01). Under bright illumination, the ruler measurements were significantly smaller (-0.15 mm) and the Colvard pupillometer measurements were greater (+0.30 mm) than the reference (P<.01). The 95% limits of agreement (LoA) between examiners were smallest for video measurements at all light levels. The remaining measures ranked from best to worst by 95% LoA were digital photography, Colvard pupillometry, ruler, and templates. CONCLUSIONS: Estimation of pupil size by digital photography was more repeatable and accurate than estimates by common clinical techniques over a wide range of illumination. Although not as quick as other methods, digital photography is relatively inexpensive, permits lasting documentation, and allows independent grading suitable for clinical research purposes.

Adult↗

Active and passive tobacco smoke exposure: a comparison of maternal and child hair cotinine levels.

The objective of this study was to compare tobacco smoke exposure in mothers and their healthy children less than 3 years old using hair cotinine (HC) levels as an objective long-term measure of exposure. Hair samples were obtained from mother/child pairs recruited from the Columbus Children's Hospital Primary Care Center, and were analyzed by radioimmunoassay to compare HC levels. Mothers were both self-reported smokers and nonsmokers. Contributing and confounding variables were assessed based on questionnaires completed by participants. Exclusion criteria for children were prematurity and presence of chronic cardiopulmonary disease. Hair samples and questionnaires were obtained from 104 mother/child pairs. Child and maternal HC levels were correlated for both self-reported maternal smokers (R2 = .13, p < .013) and self-reported maternal nonsmokers (R2 = .54, p < 001). Child HC levels were higher than maternal HC levels (1.18 ng/mg vs. .78 ng/mg, p < .001). Children of nonsmokers had higher HC levels than their mothers (.77 ng/mg vs. .35 ng/mg, p < .001), while HC levels of smokers and their children were no different (1.91 ng/mg vs. 1.92 ng/mg, p = .978). The relationship between child and maternal HC did not differ by child age, gender, or race. In conclusion, environmental tobacco smoke exposure in young children as reflected by HC is higher than expected based on prior studies of biomarkers and passive tobacco smoke exposure in adult nonsmokers.

Adult↗

Assessing bronchodilator responsiveness in infants using partial expiratory flow-volume curves.

Our objective was to compare the effectiveness of maximum forced expiratory flow measured at functional residual capacity (V'maxFRC) and the ratio of flow at 75% of the forced expiratory volume to peak forced expiratory flow (FEF(75)/FEF(peak)) for detecting bronchodilator-related changes in wheezy infants. In 55 infants (mean age, 7.8 +/- 3.1 months) with a history of recurrent wheezing, V'maxFRC and FEF(75)/FEF(peak) were measured at baseline and 15 min following nebulized albuterol. Mean results from 4 baseline and 4 postalbuterol partial expiratory flow-volume curves were compared at baseline and following bronchodilator challenge. The strength (relative effect size) of each measure for assessing change was quantified by dividing the mean of the pre- to postdifferences by the standard deviation of the differences. Mean percent predicted V'maxFRC was 41.3 +/- 34.3% at baseline and 44.4 +/- 34.0% following albuterol. Mean FEF(75)/FEF(peak) was 26.7 +/- 13.4% at baseline and 35.8 +/- 14.3% following albuterol. The mean percent change from baseline [(post-pre)/pre] in percent predicted V'maxFRC was 18.3 +/- 39.3, and for FEF(75)/FEF(peak), it was 44.1 +/- 36.8. The change in FEF(75)/FEF(peak) following albuterol was significantly greater than the change in V'maxFRC (P < 0.0001). The relative effect size for mean percent change from baseline in V'maxFRC was 0.47, and for FEF(75)/FEF(peak), 1.20. Changes in FEF(75)/FEF(peak) appear to differentiate changes in airway function following administration of a bronchodilator better than do changes in V'maxFRC.

Asthma↗

A population-based study of mortality among patients with atrial fibrillation or flutter.

PURPOSE: To determine the mortality associated with atrial flutter and atrial fibrillation in the general population. SUBJECTS AND METHODS: Using the Marshfield Epidemiologic Study Area, a database that captures nearly all medical care and deaths among its 58,820 residents, we identified patients diagnosed with atrial flutter or atrial fibrillation from July 1, 1991, through June 30, 1995. Patients were followed prospectively and compared with a group of controls without these arrhythmias. RESULTS: A total of 4775 person-years of follow-up were completed in 577 patients and 577 controls. Compared with controls, mortality among patients with atrial fibrillation or flutter was nearly 7.8-fold higher at 6 months (95% confidence interval [CI]: 4.1 to 15) and 2.5-fold higher (95% CI: 2.0 to 3.1; P < 0.0001) at the last follow-up (mean [+/- SD] of 3.6 +/- 2.3 years; range, 1 day to 7.3 years). At 6 months, mortality among patients with atrial flutter alone was somewhat greater than in controls and less than one third that of those with atrial fibrillation (with or without atrial flutter) (P = 0.02). At the last follow-up, however, mortality was greater among patients with atrial flutter (hazard ratio [HR] = 1.7; 95% CI: 1.2 to 2.6; P = 0.007), atrial fibrillation (HR = 2.4; 95% CI: 1.9 to 3.1; P < 0.0001), or both atrial arrhythmias (HR = 2.5; 95% CI: 1.9 to 3.3; P < 0.0001) when compared with controls in models that adjusted for cardiovascular risk factors. CONCLUSION: In the general population, both atrial flutter and atrial fibrillation are independent predictors of increased late mortality. The relatively benign course during the 6-month period after the initial diagnosis of atrial flutter suggests that early diagnosis and treatment of these patients may improve their long-term survival.

Aged↗

Long-term structural failure of coaxial polyurethane implantable cardioverter defibrillator leads.

Transvene models 6936/6966, a coaxial polyurethane ICD lead, may be prone to structural failure. These models comprise 54% of ICD lead failures in the authors' Multicenter Registry database. Because ICD leads perform a vital function, the clinical features, causes, and probability of Transvene 6936/6966 lead failure were determined. The Registry and United States Food and Drug Administration databases were queried for the clinical features and structural causes of the Transvene 6936/6966 lead failure, and a five-center substudy estimated the survival probability for 521 Transvene 6936/6966 implants. The mean time to failure was 4.8 +/- 2.1 years, and the estimated survival at 60 and 84 months after implant were 92% and 84%, respectively. Oversensing was the most common sign of failure (76%), and 24 patients experienced inappropriate shocks. The manufacturer's reports indicated that high voltage coil fracture and 80A polyurethane defects were the predominant causes of lead failure. Transvene models 6936 and 6966 coaxial polyurethane ICD leads are prone to failure over time. Patients who have these leads should be evaluated frequently. Additional studies are needed to identify safe management strategies.

Death, Sudden, Cardiac↗