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Biomedical subjects

E T Ballard

Publications and source records attributed to E T Ballard.

At least 19 recordsLinked to original sources

Spinal hemiepiphysiodesis correlates with physeal histomorphometric gradients.

Compression of a growth plate is known to correlate with changes to growth plate structure. The purpose of this study was to determine if the height of the physeal hypertrophic zones and chondrocyte size were directly related to the distance from a spine implant. The implant was designed with the goal of slowing spine growth asymmetrically. For stapled vertebrae, hypertrophic zone height, cell height and cell width were decreased across the coronal plane of the growth plate, with the lowest values under the staple, 8 weeks postoperatively.

Biomechanical Phenomena↗

Renal cell carcinoma as a secondary malignancy after treatment of acute promyelocytic leukemia.

Numerous children have been treated successfully for cancer and are surviving into adulthood. As this population has aged, an increasing number of secondary malignancies has emerged. Renal cell carcinoma (RCC) is a rare tumor in childhood and has not been documented previously to occur after treatment of acute promyelocytic leukemia (APL). This report describes the clinical course of APL treated in a child in whom RCC subsequently developed during adolescence approximately 5 years after therapy.

Antineoplastic Combined Chemotherapy Protocols↗

Soluble nitric oxide donor and surfactant improve oxygenation and pulmonary hypertension in porcine lung injury.

Acute lung injury (ALI) is associated with diminished surfactant activity and pulmonary hypertension. NONOates are soluble NO donors which release NO in solution. Intratracheal NONOates reduce pulmonary hypertension and improve oxygenation in ALI. We hypothesized that the pharmacologic properties of NO donors would be unaltered after surfactant admixture in vitro and that aerosolized NONOate activity would be enhanced by surfactant pretreatment in vivo. NO donors were added to saline or surfactant and analyzed for nitrite/nitrate production and aortic ring vasodilation. Surfactant did not alter nitrate/nitrite production or aortic ring vasodilation. A porcine model of ALI with pulmonary hypertension was produced using intravenous oleic acid. Animals were assigned to Surfactant-Saline, Surfactant-NONOate, Saline-Saline, or Saline-NONOate groups. Saline or surfactant was instilled into the trachea, followed by gas exchange, pulmonary function, and hemodynamic measurements. NONOate or saline was then aerosolized, and additional data were collected. Oxygenation was improved in the Surfactant-NONOate group, while pulmonary hypertension was selectively reduced in both NONOate groups. Aerosolized NONOate following surfactant pretreatment improves oxygenation and reduces pulmonary hypertension in ALI.

Amino Acids, Diamino↗

The relationship of hepatotoxic risk factors and liver histology in methotrexate therapy for juvenile rheumatoid arthritis.

OBJECTIVE: To examine the relationship between hepatotoxic risk factors and liver histopathology in patients with juvenile rheumatoid arthritis (JRA) treated with methotrexate (MTX). STUDY DESIGN: We graded the histology of 33 percutaneous liver biopsy specimens from 25 patients with JRA treated at Children's Hospital Medical Center, Cincinnati, Ohio, using the Roenigk Classification Scale. Stepwise linear and logistic regression analyses were performed to examine the relationship of the Roenigk grade and presence of liver fibrosis of biopsy specimens with potential risk factors. RESULTS: Twenty-seven biopsy specimens (82%) were classified as grade I, 4 (12%) as grade II, and 2 (6%) as grade IIIA; none demonstrated significant fibrosis. The frequency of biochemical abnormalities (P <.001) and body mass index (P =.05) were the only risk factors found to significantly relate to the Roenigk grade. The following factors were not significantly associated with the Roenigk grade: age, gender, disease duration, JRA subtype and course, duration of MTX administration, weekly MTX dose, cumulative dose of MTX, route of MTX administration, use of folic acid supplementation, concurrent use of other medications, and potential hepatotoxic comorbidities. CONCLUSIONS: Serial biochemical abnormalities are significantly associated with Roenigk grade and the presence of liver fibrosis. These findings concur with studies of patients with rheumatoid arthritis, suggesting that guidelines for monitoring MTX hepatotoxicity in rheumatoid arthritis may be applicable to patients with JRA.

Adolescent↗

Effect of superoxide dismutase on a rabbit model of chronic allergic asthma.

BACKGROUND: In bronchial asthma, inflammatory cells infiltrating the airway mucosa release oxygen radicals that cause tissue damage and amplify the airway inflammation. Antioxidant enzymes may have a protective effect on the airways. OBJECTIVE: The purpose of this study was to determine whether treatment of a rabbit model of chronic allergic asthma with the antioxidant enzyme superoxide dismutase conjugated to polyethylene glycol will protect the airways from oxygen radical injury, decrease airway inflammation, and attenuate the asthmatic response. METHODS: New Zealand white rabbits were sensitized to ragweed. Baseline histamine PC30, ragweed PD30, and early and late phase asthmatic response to ragweed bronchial challenge were measured. The rabbits were then randomized into two groups that received every 48 hours an intravenous dose of either superoxide dismutase-polyethylene glycol 10,000 U/kg or inactivated superoxide dismutase-polyethylene glycol as control, followed by a 1-hour exposure to aerosolized ragweed extract. After 4 weeks the rabbits had a second bronchial challenge, were sacrificed, and lung histology was studied. RESULTS: On the posttreatment challenge, the superoxide dismutase-polyethylene glycol group had a rise in ragweed PD30, while the control group had no change in ragweed PD30, and two of five rabbits in the superoxide dismutase-polyethylene glycol group did not have an early or late phase asthmatic response, while all rabbits in the control group had an asthmatic response. There was no significant difference in lung histology between both groups. CONCLUSION: A rabbit model of chronic allergic asthma treated with superoxide dismutase-polyethylene glycol showed a trend of improvement in airway responsiveness but no significant effect on airway inflammation.

Animals↗

Aerosolization of novel nitric oxide donors selectively reduce pulmonary hypertension.

OBJECTIVES: Inhaled nitric oxide (NO) reduces pulmonary hypertension in acute respiratory failure. Soluble nitric oxide donors (NO/nucleophile adducts-NONOates) are less cumbersome to deliver and may offer clinical advantage compared with inhaled NO. The objective of this study was to examine the pulmonary and systemic hemodynamic effects of tracheal aerosolization of a new class of NONOates in a porcine model of experimentally induced pulmonary hypertension. DESIGN: Prospective, randomized, controlled study. SETTING: Research laboratory. SUBJECTS: Yorkshire pigs (n = 18), weighing 11.4 to 16.4 kg. INTERVENTIONS: In anesthetized, mechanically ventilated, instrumented pigs, steady-state pulmonary hypertension (SSPH) was induced using a thromboxane agonist (U46619). Control animals received tracheal aerosolization of saline (n = 6); EP/NO animals received tracheal aerosolization of ethylputreanine NONOate (EP/ NO, n = 6); and DMAEP/NO animals received aerosolized 2-(dimethylamino) ethylputreanine NONOate (DMAEP/NO, n = 6). MEASUREMENTS AND MAIN RESULTS: Mean pulmonary (MPAP) and mean systemic arterial pressures (MAP), atrial pressures, cardiac output, and arterial blood gases were measured following drug instillation. DMAEP/NO animals had significant reductions in pulmonary vascular resistance index (PVRI) and MPAP at all time points compared with SSPH and control animals (p < .05), while systemic vascular resistance index did not change. EP/NO animals had a significant reduction in PVRI and MPAP at some time points compared with SSPH and control animals. For both NONOate-treated animal groups, MAP and cardiac index did not change significantly compared with SSPH and control animals (p < .05). CONCLUSIONS: In this porcine model of pulmonary hypertension, intratracheal aerosolization of soluble NO donors results in sustained reduction of pulmonary hypertension without reducing systemic arterial pressure. Intermittent aerosolization of NONOates may be an alternative to continuously inhaled NO in the treatment of acute pulmonary hypertension.

Acute Disease↗

Aerosolized soluble nitric oxide donor improves oxygenation and pulmonary hypertension in acute lung injury.

Acute respiratory distress syndrome (ARDS) is a major cause of morbidity and mortality in critically ill patients. The associated ventilation/perfusion mismatch and pulmonary hypertension are amenable to treatment with inhaled nitric oxide (NO) gas. Compounds formed by reacting NO with various nucleophiles (NONOates) release NO spontaneously and induce vasodilation. Intratracheally administered NONOates result in selective reduction in pulmonary hypertension. We hypothesized that a nebulized NONOate would improve oxygenation and reduce pulmonary vascular resistance in oleic acid-induced acute lung injury and pulmonary hypertension. Pigs underwent catheterization of the pulmonary artery, left atrium, and right atrium, and a flow probe was positioned around the pulmonary artery. Acute lung injury and pulmonary hypertension were induced with intravenous oleic acid. Animals were randomly assigned to receive either nebulized saline or the NONOate 2-(dimethylamino)ethylputreanine/NO (DMAEP/NO). Hemodynamic, gas exchange, pulmonary function, methemoglobin, and nitrite/nitrate measurements were obtained for 60 min. Animals in the DMAEP/NO group had improvement in PaO2 as compared with control animals (from 139 +/- 19 mm Hg to 180 +/- 19 mm Hg in the DMAEP/NO group [n = 6]; and from 144 +/- 6 mm Hg to 150 +/- 9 mm Hg in the saline group [n = 6], p < 0.05). After aerosol treatment, animals in the DMAEP/NO group had a greater reduction in pulmonary vascular resistance index (PVRI) than did control animals (from 81 +/- 17 dyne. s/cm5/kg to 34 +/- 8 dyne. s/cm5/kg; and from 104 +/- 16 dyne. s/cm5/kg to 64 +/- 11 dyne. sec/cm5/ kg in the saline group at 60 min, p < 0.05). There were no differences between the groups in systemic vascular resistance index (SVRI), cardiac index (CI), methemoglobin, nitrite/nitrate, or lung pathology scores. We conclude that DMAEP/NO improves oxygenation and has selective pulmonary vasodilating properties without causing significant systemic toxicity in this porcine model of acute lung injury.

Administration, Inhalation↗

The long-term effect of methotrexate therapy on the liver in patients with juvenile rheumatoid arthritis.

OBJECTIVE: To determine if the long-term use of methotrexate (MTX) in juvenile rheumatoid arthritis (JRA) is associated with the development of significant liver fibrosis, and to describe the presence of risk factors for liver fibrosis in patients with JRA. METHODS: Needle biopsies of the liver were performed on a cross-section cohort of 14 patients with JRA who had received a total cumulative dose of MTX that was either > 3,000 mg or > 4,000 mg/1.73 m2 of body surface area. Biopsy samples were independently graded according to the Roenigk Classification Scale by 2 pathologists. The presence of risk factors for MTX hepatotoxicity, especially biochemical abnormalities reflective of liver injury and alcohol consumption, were assessed. RESULTS: Thirteen biopsy samples (93%) were classified as grade I, and 1 (7%) as grade II; none demonstrated significant fibrosis. However, histologic abnormalities were found in 13 biopsy samples (93%). Only 2 patients (14%) consumed more than 1 alcoholic drink per month. Thirteen patients (93%) had biochemical abnormalities while being treated with MTX, but only 5 patients (36%) had at least 1 determination in which the aspartate or alanine aminotransferase elevation was > 3 times the upper limit of normal. CONCLUSION: Long-term use of MTX for JRA does not appear to be associated with the development of significant liver fibrosis. Although nearly all patients had minor histologic changes, no significant clinical consequences were apparent. A prospective study of a larger population will more accurately define the incidence of MTX-related liver fibrosis and appropriate monitoring guidelines in JRA.

Adolescent↗

Meningioangiomatosis of the brain stem. Case report.

The case is reported of meningioangiomatosis of the brain stem in a 3 1/2-year-old girl who suffered from vomiting, left facial weakness, difficulty in swallowing, and ataxia. This is believed to be the first reported case of meningioangiomatosis in the brain stem. Computerized tomography showed an intensely enhancing hyperdense mass in the left restiform body. Magnetic resonance imaging revealed that the lesion was isointense to gray matter on the T1-weighted image and hypointense on the T2-weighted image, with a surrounding zone of high T2 signal and intense enhancement. Angiography was normal. Surgical exploration demonstrated an intramedullary firm mass that was partially resected. Histologically, the mass consisted of a low-grade lesion of meningeal origin with spindle cells in a whorling pattern that were occasionally focused around small vessels. On 2-year follow-up imaging, the lesion remains unchanged in size. Certain particularities of this lesion are discussed in the context of the literature.

Brain Stem↗

Growth patterns of human neuroblastoma xenografts and their relationship to treatment outcome.

BACKGROUND: Several investigators have reported the ability to establish xenografts in nude mice from children with neuroblastomas, but a correlation of prognosis with this establishment and the growth patterns of the neuroblastomas has not been reported. METHODS: Tumor specimens from 58 children with neuroblastomas were heterotransplanted into BALB/c nude mice. In 34 patients, heterotransplantation was done before therapy; in 24 patients, tumors were obtained after at least one course of chemotherapy or radiation therapy. The histology, cytogenetics, and growth characteristics of serial passages of the xenografts were studied. RESULTS: The engraftment rate was 34%. Neuroblastomas with diploid chromosome numbers did not engraft. Chromosomal abnormalities involving 1p were seen in more than 50% of the xenografts. Cytogenetic features were retained between original tumors and resultant xenografts. Xenografts could be established only from tumors with unfavorable histology, as defined by Shimada classification criteria. The histology of each xenograft line was strikingly similar, and each was highly undifferentiated. Engraftment rates, doubling times, and lag times did not vary appreciably between xenografts established from treated tumors compared with xenografts established from untreated tumors. There was no correlation between doubling or lag times and prognosis. Patients whose tumors engrafted had only a 5% 3-year survival rate. CONCLUSIONS: From these results, it appears that successful engraftment is the most important prognostic indicator for patients with neuroblastomas. Because of the commonality of the histologic features and the stability of the tumor clones from patients before and after heterotransplantation, these xenografts may be useful as an in vivo model for studying drug resistance and for designing treatment regimens.

Animals↗

Plain film identification of inverted Meckel diverticulum.

Inversion is a potentially serious complication of Meckel diverticulum. Since inversion provokes gangrene and small bowel obstruction, diagnosis by enteroclysis or imaging studies can conflict with the need for timely surgical intervention. We have noted that plain films may predict this lesion when a solitary mottled polypoid lesion occupies the ileum at the site of a small bowel obstruction.

Child, Preschool↗

Digital schwannoma in a skeletally immature child.

Soft tissue neoplasms of the hand are rare in general and even more uncommon in children. The most commonly considered diagnoses include ganglion, inclusion cyst, lipoma, subcutaneous foreign body granuloma, and tendon sheath xanthoma. Aside from pressure sensitivity, masses on the palmar aspect of the hand are often asymptomatic. The case reported here identifies a primary neural neoplasm (neurilemmoma) that involves a small peripheral nerve in the hand of a twelve-year-old child. The patient had no neurologic symptoms and illustrates the need to include neurilemmomas in the differential diagnosis of hand masses in children.

Child↗

Necrotizing tracheobronchitis: case report.

A 33-week-gestation infant with respiratory distress syndrome is reported. At five days of age, acute life-threatening tracheal obstruction occurred, which was relieved after removal of a plug during bronchoscopy. Histologic examination of the plug revealed partially necrotic tracheal mucosa, compatible with the diagnosis of necrotizing tracheobronchitis. At 31 days of age, obstruction recurred due to the development of a tracheal stricture, which resolved after tracheal reintubation (to maintain patency) and corticosteroid therapy. Tracheal stricture may be a long-term complication of necrotizing tracheobronchitis, when the initial episode does not lead to death from obstruction.

Bronchitis↗

Immunologic, morphologic and chromosomal characterization of a cell line (TC78) established from a child with acute lymphoblastic leukemia.

We characterized a cell line established from bone marrow cells from a child with acute lymphoblastic leukemia. This cell line, TC78, had lymphoblastic morphology and was cytoplasmic peroxidase and esterase negative. The cells did not have T- or B-cell properties such as E- or EAC-rosette forming ability, reactivity with monoclonal T-cell or B2 antibodies, or immunoglobulin synthesis. We concluded that TC78 was a pre-pre B-cell line based on the following monoclonal antibody staining pattern: BA-1+, BA-2+, cALLa+, Ia+, 2H7+ and OKB2+. Growth in 'Dickie' culture and reactivity with 1G10 myeloid antibody suggested coexpression of lymphoid and myeloid characteristics. However, 1G10 expression proved dependent on culture conditions, illustrating one caveat in application of monoclonal antibodies in lineage determination.

Antigens, Neoplasm↗

Characteristics of 85 pediatric tumors heterotransplanted into nude mice.

81 primary pediatric tumors and 4 tumor lines were heterotransplanted into nude mice with an overall success rate of 38.3%. There was variability in success between tumor types. Bone sarcomas were highly successful while brain, lymphoid, and benign tumors in general did poorly. With increasing passage lag times decreased but actual growth rates in general did not change. Results suggested that tumors obtained prior to therapy which grew in nude mice were more likely to recur in the patient. During the observation period 7 spontaneous mouse tumors developed, distinguished from human tumors by histology, cytogenetics, and isoenzyme studies.

Animals↗

Clinical and occult testicular leukemia in long-term survivors of acute lymphoblastic leukemia.

Twenty-nine of 60 boys with acute lymphoblastic leukemia survived for more than 30 months and were potential candidates for discontinuation of therapy. Six patients developed overt clinical testicular leukemia: one at 34 months from diagnosis while receiving therapy and five at three to 17 months after therapy was stopped. Elective wedge biopsy of the testes has become part of the evaluation prior to discontinuation of therapy since 1977. Six of 18 boys had microscopic evidence of leukemic infiltration of the testes: four with diffuse involvement and two with focal clusters of leukemic cells. Testicular biopsy is recommended at the time of discontinuation of therapy and perhaps early in the course of the disease, although a negative biopsy does not exclude some focal lesions. The eventual outcome of those with occult testicular leukemia remains to be determined.

Child↗