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Biomedical subjects

G B Mallory

Publications and source records attributed to G B Mallory.

At least 37 records · Page 2Linked to original sources

Longitudinal follow-up of lung function from childhood to adolescence in prematurely born patients with neonatal chronic lung disease.

We investigated whether early lung function abnormalities in prematurely born children with a history of chronic lung disease improve in late childhood and adolescence. We performed a prospective, longitudinal evaluations of pulmonary function over an 8 year period. In seventeen patients from the age (mean +/- SD) of 8.2 +/- 1.2 years to the age of 15.1 +/- 1.6 years. They had been born at 29.1 +/- 1.9 weeks of gestation, with a birthweight of 1120 +/- 190 g, and they had received supplemental oxygen, with or without mechanical ventilation, for 40.4 +/- 23.8 days during the neonatal period. They all had radiographic evidence of chronic lung disease at 4 weeks of age. Annual measurements of lung volumes using the helium dilution technique, and of airway function with spirometry and maximal expiratory flow-volume curves over a 5 to 8 year period, were obtained. The results indicated that total lung capacity (TLC) and vital capacity (VC) were within the predicted normal range in all patients and increased over time. In contrast, the initially abnormal residual volume (RV) and RV/TLC ratio decreased over time, suggesting gradual resolution of air-trapping. The peak expiratory flow rate (PEFR), forced expiratory volume in 1 second (FEV1), and the ratio FEV1/FVC remained at or above the predicted normal range in all patients. FEF25-75, FEF50, and FEF75 were within normal limits in eight patients and abnormally low (more than 2 SD below the predicted normal value) in the remaining nine patients, indicating small airway obstruction. Eight of the nine patients with lower airway obstruction showed significant response to inhaled bronchodilator, and four responded to a histamine challenge. None of the eight patients with normal airway function responded to histamine, but four responded to bronchodilators. The perinatal history, family history of asthma, and exposure to smoking were similar in patients with and without airway obstruction. The height and weight were and remained within the normal range. We conclude that gradual normalization of air-trapping continues well into adolescence in virtually all patients with a history of prematurity and chronic lung disease. in contrast, airflow obstruction may persist but does not get worse later in life. Although chronic airflow obstruction probably is the consequence of injury to the small airways during the neonatal period, it is present in only some of the children, and it does not appear to be directly related to the perinatal history. Finally, there is evidence that airway hyperresponsiveness may be a contributing factor to the development and/or persistence of airflow obstruction in chronic lung disease of prematurity.

Bronchopulmonary Dysplasia↗

Hepatic drug clearance in patients with mild cystic fibrosis.

The plasma disposition of three model substrates (lorazepam, indocyanine green, and antipyrine) and the formation clearance of antipyrine metabolites (3-hydroxymethylantipyrine, norantipyrine, and 4-hydroxyantipyrine) were evaluated in 15 subjects with mild cystic fibrosis and in 15 healthy control subjects. Plasma clearance was significantly greater in patients with cystic fibrosis for both lorazepam (1.7 +/- 0.4 versus 1.2 +/- 0.5 ml/min/kg) and indocyanine green (14.2 +/- 6.1 versus 9.1 +/- 3.0 ml/min/kg). In contrast, the clearance of antipyrine was not significantly different (1.0 +/- 0.7 versus 0.8 +/- 0.3 ml/min/kg), but the formation clearance for 3-hydroxymethylantipyrine was significantly greater in patients with cystic fibrosis. Lorazepam and antipyrine apparent steady-state volume of distribution were not different between groups. These results suggest that clearance of drugs that undergo conjugation (e.g., lorazepam) or biliary excretion (e.g., indocyanine green) is increased in patients with mild cystic fibrosis. In contrast, the increased formation clearance of only one antipyrine metabolite suggests that alterations in clearance of drugs metabolized by cytochrome P450 enzymes are substrate specific and isoform specific in patients with cystic fibrosis.

Adolescent↗

Atrial flutter: a newly recognized complication of pediatric lung transplantation.

BACKGROUND AND METHODS: Atrial flutter after pediatric lung transplantation has not previously been reported. We reviewed the records of 78 children who underwent lung transplantation at our institution to characterize the incidence and clinical course of postoperative atrial flutter. The diagnosis was based on either a surface or transesophageal electrocardiogram that demonstrated a fixed cycle length atrial tachycardia that did not require ventricular participation. RESULTS: Atrial flutter occurred in seven of 62 (11.3%) patients who underwent bilateral sequential lung transplantation, zero of 10 patients after single lung transplantation, and zero of six patients after heart-lung transplantation. Ages of the patients with atrial flutter ranged from 2.5 months to 14 years. Electrocardiographic findings among patients varied with respect to p-wave morphology and atrioventricular conduction. No patient had a prior atrial arrhythmia or coexisting structural cardiac disease. None had atrial flutter in relation to a rejection episode. Two patients had atrial flutter transiently during the first postoperative day, but it resolved spontaneously. Five patients had recurrent atrial flutter that began 13 +/- 7 days after the operation. The mean cycle length of atrial flutter was 196 +/- 65 msec. The arrhythmia was unresponsive to digoxin in four patients to whom it was administered. It was controlled with procainamide in four patients and with flecainide in one. At 1 and 6 months after lung transplantation, procainamide was discontinued in two patients without recurrence. One patient died of bronchiolitis obliterans 6 months after the operation while still receiving flecainide. Two patients continue to receive procainamide 4 and 7 months after transplantation. CONCLUSIONS: (1) Atrial flutter commonly occurs after bilateral lung transplantation in children. (2) Electrocardiographic manifestations are variable. (3) Type 1 antiarrhythmic agents provide satisfactory control.

Adolescent↗

Major medical complications of lung transplantation: a pediatric perspective.

The major challenges to success in the modern era of lung transplantation are the problems of graft infection and rejection. The lung is the only solid organ in which infection is virtually guaranteed after transplantation. Clinical management of lung transplantation candidates includes testing for previous and current infections and appropriate immunizations. An aggressive prophylactic regimen against infection after lung transplantation is tailored to the individual patient's underlying disease and infection history. A high index of suspicion and frequent testing, including rapid viral diagnosis and flexible fiberoptic bronchoscopy with bronchoalveolar lavage, have become the standard in posttransplantation medical management. The problems of acute and chronic graft rejection seem to be more frequent and severe in lung transplant recipients than in those who receive other solid organ transplants. Anticipation and aggressive treatment of early acute graft rejection are critical aspects of the care of patients in the first months after transplantation. Bronchiolitis obliterans, which is caused by chronic graft rejection, is the biggest obstacle to long-term survival. New diagnostic and therapeutic strategies to detect and treat the infectious and immunologically mediated complications of lung transplantation will be needed in the future.

Acute Disease↗

Lung transplantation in infancy and early childhood.

BACKGROUND: Experience with lung transplantation in infants and young children is limited. Small size, vulnerability to infection, and limited modalities for rehabilitation and surveillance of the transplanted lung make this group particularly challenging. METHODS: We reviewed the course of all children up to the age of 25 months who underwent lung transplantation at two centers between July 1990 and February 1995. RESULTS: Lung transplantation was performed in 17 patients under the age of 25 months, with concurrent cardiac repair in 14. Prior thoracic surgery had been performed in 12; six patients had mechanical ventilation, and three were supported with extracorporeal membrane oxygenation while waiting for lungs. The mean waiting time was 37 days (range 1 to 197 days). Hospital survival was 12 of 17 (71%); there was one late death. Early deaths were due to hemorrhage (two patients), cytomegalovirus and lymphoproliferative disease (one patients), and viral pneumonitis (two patients). The one late death was due to overwhelming gastroenteritis of unknown origin. One additional patient had graft failure caused by viral pneumonitis and underwent successful retransplantation. Bronchial stenosis occurred at 3 of 33 anastomoses. At a mean follow-up of 22 months, surviving patients were well, without supplemental oxygen, and, although small in stature, had normal linear growth. CONCLUSIONS: Lung transplantation is a reasonable therapy for very young patients with limited life expectancy and no other therapeutic alternative, with outcomes comparable with those achieved in older patients. Early recognition of lung transplant candidates and advances in the prevention, diagnosis, and treatment of viral illness may improve survival in these patients.

Actuarial Analysis↗

A new technique for transbronchial biopsy in infants and small children.

We describe a technique of transbronchial biopsy (TBB) in small children, using a plastic suction catheter as the working channel through which biopsy forceps are introduced. An ultrathin (2.2 mm) flexible fiberoptic bronchoscope (FFB) was used to direct the catheter visually into the desired lung segment and to biopsy selectively. This technique was used nine times to obtain biopsy specimens in six different patients, ranging in age from 3 months to 3 and 4/12 years (mean, 19.2 months). Adequate specimens were obtained in eight of nine procedures (89%). Complications included one pneumothorax that did not require evacuation and one episode of sedation-induced hypoventilation that required brief bag-mask ventilation. No significant bleeding occurred. This technique enabled us to obtain lung tissue in infants and small children without resorting to general anesthesia and rigid bronchoscopy.

Biopsy, Needle↗

Lung transplantation in children and young adults with cardiovascular disease.

Single or bilateral lung transplantation was performed in 20 patients with pulmonary hypertension or an inadequate pulmonary vascular bed; all but 1 had congenital heart disease. The average age was 6.3 years (range, 3 months to 23.9 years). All were in New York Heart Association class IV, and 6 were hospitalized and receiving intensive support before transplantation. Hospital survival was 70% (14/20), with three additional deaths at 7, 11, and 27 months. A prior thoracic operation contributed to three of six hospital deaths from hemorrhage. All late deaths were due directly or indirectly to obliterative bronchiolitis. At a mean follow-up of 19 months (range, 2 to 48 months), 10 of 11 survivors are in New York Heart Association class I. Survival after hospital discharge and incidence of obliterative bronchiolitis are similar in a contemporary group of 41 patients of comparable age who underwent lung transplantation for pulmonary disease (p = not significant). Single or bilateral lung transplantation is an acceptable therapy for children with pulmonary hypertension, congenital heart disease, or both. Further investigation in the areas of pretransplantation survival, operative risk factors, and long-term outcome of single-lung recipients and recipients with hemodynamically insignificant intracardiac lesions are needed to develop optimal decision-making strategies for these patients.

Adolescent↗

Lung transplantation for congenital pulmonary vein stenosis.

BACKGROUND: Congenital pulmonary vein stenosis is a uniformly fatal disease when left untreated. Transcatheter techniques (for example, balloon dilation and stent placement) have proved to be only temporizing measures, and previous surgical attempts at treatment of this entity have provided little improvement and few survivors. METHODS: Over the last 4 years, 6 patients with congenital pulmonary vein stenosis have been treated at our institution, 3 of whom underwent bilateral sequential lung transplantation. RESULTS: The 3 patients who underwent bilateral lung transplantation are alive and well 6 to 24 months after transplantation. The other 3 died of complications of the disease before donor lungs became available. CONCLUSIONS: Making the diagnosis of congenital pulmonary vein stenosis requires a high index of suspicion, and referral for lung transplantation should be made as soon as the diagnosis is reached. Lung transplantation has resulted in good-quality short to medium-term survival for 3 patients with this otherwise untreatable disease.

Constriction, Pathologic↗

Use of nasal continuous positive airway pressure as treatment of childhood obstructive sleep apnea.

OBJECTIVE: To determine the safety and efficacy of nasal continuous positive airway pressure (CPAP) for obstructive sleep apnea (OSA) during childhood and the effects of growth and maturation on CPAP requirements. DESIGN: Retrospective study with use of a written questionnaire administered to pediatric practitioners treating sleep disorders. SETTING: Nine academic pediatric sleep disorders centers. RESULTS: Data were obtained for 94 patients. Three percent of patients receiving CPAP were less than 1 year, 29% were 1 to 5 years, 36% were 6 to 12 years, and 32% were 13 to 19 years of age; 64% were boys. The longest duration of CPAP use was 4 years. Indications for CPAP included OSA associated with obesity (27%), craniofacial anomalies (25%), idiopathic OSA persisting after adenoidectomy and tonsillectomy (17%), and trisomy 21 (13%). Continuous positive airway pressure was effective in 81 patients (86%), in one patient it was unsuccessful, and in 12 patients compliance was inadequate. The median pressure required was 8 cm H2O (range, 4 to 20 cm H2O); pressure requirements were independent of age or diagnosis. Twenty-two percent of patients eventually required a modification of CPAP levels. Complications of CPAP were minor. Sixty-four percent of centers reported difficulty in obtaining funding for CPAP. CONCLUSIONS: Continuous positive airway pressure is safe, effective, and well tolerated by children and adolescents with OSA. Experience in infants is limited. As pressure requirements change with patient growth, we recommend that CPAP requirements be regularly reevaluated over time. The marked center-to-center variability in CPAP use suggests that specific indications for this therapy require clarification.

Adolescent↗

Estimation of total lung capacity from chest radiography and chest CT in children: comparison with body plethysmography.

OBJECTIVE: The purpose of this study was to evaluate two methods of estimating lung volume using chest radiographs and one using chest CT in children. Estimates made with these techniques were compared with total lung capacity calculated with body plethysmography. MATERIALS AND METHODS: CT scans and posteroanterior and lateral radiographs of the chest were obtained in 21 children (14 girls and seven boys) for follow-up evaluation after lung transplantation. Lung volume was measured by CT using a previously validated technique of tracing the margins of the lungs on each axial CT scan. Two methods were used to estimate lung volume on chest radiographs: a technique previously described in adults and children that requires 21 measurements on posteroanterior and lateral radiographs, and a modification of a simplified technique previously reported in adults that uses only two measurements on a posteroanterior radiograph alone. Estimated lung volumes from CT and from both methods using chest radiographs were compared with total lung capacity determined from body plethysmography using regression analysis, and 95% prediction intervals were generated. RESULTS: All three methods of estimating lung volumes from radiographs correlated well with total lung capacity from plethysmography (r = .89-.92). However, we found no statistically significant or clinically meaningful difference among the methods of estimating lung volume. CONCLUSIONS: Lung volumes in children can be accurately estimated from specific measurements made on chest radiographs and on CT scans. Of the two methods tested with chest radiographs, the technique that required only two measurements from a posteroanterior chest radiograph was as accurate as the more complicated technique that required 21 measurements.

Adolescent↗

Isolated lung transplantation in children: pathological diagnosis and incidence of pulmonary complications.

The pathological findings in the allografts of 14 children who underwent lung transplantation (LT) at St. Louis Children's Hospital, St. Louis, MO, in the period between July 1990 and May 1992 were reviewed. The study is based on histological analysis of 63 transbronchial biopsy (TBB) specimens, eight open lung biopsy specimens, and three pneumonectomy specimens. The mean age at transplantation was 10.5 years (range, 1 to 17 years) and the average follow-up period was 5.7 months. Sufficient tissue for an adequate pathological examination was obtained in 58 (92%) TBB specimens. Each specimen consisted of a mean of 6.12 tissue fragments, but only 4.79 fragments contained actual lung parenchyma for suitable examination. Ten patients (71%) had 23 biopsy-proven episodes of acute rejection with a frequency of 1.64 episodes per patient. The first episode was documented at a mean of 19 days after transplantation. Six patients (42.8%) developed bronchiolitis obliterans (BO). The definitive diagnosis of this condition was made either by open lung biopsy (n = 3) or on allograft pneumonectomy (n = 1), and it was infrequently recognized by TBB. Four of the six patients died less than 9 months after the diagnosis of BO was made, indicating the grave consequences of this complication. Two other deaths were attributed to the development of posttransplantation lymphoproliferative disorders.

Adolescent↗

Diagnosis of pulmonary complications associated with lung transplantation in children: value of CT vs histopathologic studies.

OBJECTIVE: The purpose of this study was to compare the CT findings with those of histopathologic studies to determine if CT can be used to differentiate between the pulmonary parenchymal complications that occur in children after lung transplantation. MATERIALS AND METHODS: Seventeen children who underwent 14 bilateral and three single lung transplantations were studied. The study population included nine girls and eight boys 2-16 years old (mean, 11 years). CT scans were examined for evidence of interlobular septal thickening, air-space consolidation, ground-glass opacities, nodules, bronchial dilatation, decreased vascularity, and pleural effusions. Thirty-one histopathologic diagnoses from 25 transbronchial biopsies were available for comparison with CT findings. The final histopathologic diagnoses were acute rejection (n = 10), chronic rejection (n = 6), infection (n = 7), nonspecific findings (n = 4), and no abnormalities (n = 4). RESULTS: No significant difference was noted in the CT findings in patients with acute rejection, chronic rejection, and infection. CONCLUSION: In this limited study of children, CT findings were not helpful in differentiating between the different parenchymal pulmonary complications associated with lung transplantation. On the basis of these preliminary findings, we recommend caution in suggesting specific diagnoses based on CT scans without histologic proof.

Bronchiolitis Obliterans↗

Pediatric lung transplantation. Indications, techniques, and early results.

From July 1990 to April 1993, 36 lung transplantations in 33 patients were performed in our pediatric transplant program (0.25 to 23 years, mean age 10.3 years). Eight children had been continuously supported with a ventilator for 3 days to 4.5 years before transplantation and three were supported by extracorporeal membrane oxygenation. Indications for lung transplantation in this pediatric population included the following: cystic fibrosis (n = 13), pulmonary hypertension, and associated congenital heart disease (n = 10), pulmonary atresia, ventricular septal defect and nonconfluent pulmonary arteries (n = 3), pulmonary fibrosis (n = 6), and acute respiratory distress syndrome (n = 1). Three children underwent retransplantation for acute graft failure (n = 2) or chronic rejection (n = 1). Pulmonary fibrosis was related to complications of treatment of acute of myelogenous leukemia with bone marrow transplantation in two children and to bronchiolitis obliterans, bronchopulmonary dysplasia, interstitial pneumonitis, and Langerhans cell histiocytosis in four others. Thirteen children underwent lung transplantation and concomitant cardiac repair. Bilateral lung transplantation, ventricular septal defect closure and pulmonary homograft reconstruction of the right ventricular outflow tract to the transplanted lungs was performed in three children by means of a new technique that avoids the need for combined heart-lung transplantation. Two patients had ventricular septal defect closure and single lung transplant for Eisenmenger's syndrome, two had ligation of a patent ductus arteriosus and transplantation, three additional children underwent atrial septal defect closure and lung transplantation, and two underwent lung transplantation for congenital pulmonary vein stenosis. Eight early deaths and three late deaths occurred (actuarial 1-year survival 62%). Lung transplantation in children has been associated with acceptable early results, although modification of the adult implantation technique has been necessary. Lung transplantation and repair of complex congenital heart defects is possible; heart-lung transplantation may only be required for patients with severe left heart dysfunction and associated pulmonary vascular disease. Bronchiolitis obliterans remains a major concern for long-term graft function in pediatric lung transplant recipients.

Adolescent↗

Linear IgA bullous dermatosis in a neonate.

A newborn black boy had two facial blisters at birth that progressed to bullous lesions over the trunk, genitals, extremities, and oral and tracheal mucosa. A biopsy specimen demonstrated a subepidermal bulla with mixed eosinophilic and neutrophilic, inflammatory infiltrate. Direct immunofluorescence showed linear IgA, IgG, and C3 depositions along the basement membrane zone, consistent with a diagnosis of childhood linear IgA bullous dermatosis (chronic bullous dermatosis of childhood). The skin disease was controlled with combined prednisone and dapsone. This is the youngest reported patient with the disease. Linear IgA bullous dermatosis should be considered in the differential diagnosis of blistering diseases of the newborn, and immunofluorescence should be performed on a skin biopsy specimen.

Basement Membrane↗

Pediatric lung transplantation: radiographic-histopathologic correlation.

Chest radiographic and histopathologic findings were retrospectively reviewed to determine the spectrum of findings in 16 children who underwent a total of 19 lung transplantations. Radiographs were evaluated for air-space disease, interstitial disease, Kerley B lines, pleural fluid, and cardiac size, and the interval from transplantation to the onset of complications was determined. Radiographic findings were correlated with 62 histopathologic diagnoses obtained from 51 transbronchial and open lung biopsy specimens. The final histopathologic diagnoses were acute rejection (n = 19), chronic rejection (n = 8), infection (n = 11), lymphoproliferative disorder (n = 4), and nonspecific (n = 20). The radiographic patterns of the complications were not significantly different. Seventy-nine percent (15 of 19) of episodes of acute rejection and 64% (seven of 11) of episodes of infection occurred within 5 weeks of transplantation, while 63% (five of eight) of the episodes of chronic rejection occurred after this period. Since chest radiographs are nonspecific, caution should be exercised in basing clinical decisions only on the radiographic pattern in the absence of corroborative clinical and histopathologic findings.

Adolescent↗

Pediatric lung transplantation for pulmonary hypertension and congenital heart disease.

Five children underwent lung transplantation for end-stage pulmonary hypertension and respiratory insufficiency associated with congenital heart disease. One (17 mo) had pulmonary hypertension with a patent ductus arteriosus and required two periods of preoperative extracorporeal membrane oxygenation before successful bilateral sequential lung transplantation. One (21 mo) required bilateral lung transplantation for pulmonary hypertension and bronchopulmonary dysplasia associated with iatrogenic injury to the left pulmonary artery. This child also had patent ductus arteriosus ligation and preoperative catheter closure of an atrial septal defect. Extracorporeal membrane oxygenation was required for early postoperative pulmonary support. One child underwent right single-lung transplantation and closure of an atrial septal defect for pulmonary hypertension. Two patients had single-lung transplantation for Eisenmenger's syndrome: 1 with muscular inlet ventricular septal defect closure, atrial septal defect closure, and right single-lung transplantation; 1 with ventricular septal defect closure, patent ductus arteriosus ligation, right ventricular outflow tract patch repair, and single-lung transplantation. All patients survived operation, with one late death (lymphoproliferative disease). The 4 survivors are all ambulatory without oxygen and have evidence of normal pulmonary artery pressure 9 to 12 months after transplantation.

Adolescent↗

Longitudinal changes in lung function during the first three years of premature infants with moderate to severe bronchopulmonary dysplasia.

Bronchopulmonary dysplasia (BPD) is a chronic obstructive pulmonary disease of prematurely born infants following prolonged mechanical ventilation and oxygen therapy. Developmental changes in pulmonary function of children with BPD during their early years have been difficult to study. We longitudinally studied maximal expiratory flow-volume curves by the forced deflation technique in 11 infants who had previous tracheostomy with moderate to severe BPD. Patients were classified into: those who were mechanically ventilated for less than 5 months (Group A), and those who were ventilated for 10 or more months (Group B). At 6 months of age, forced vital capacity (FVC) was 28.1 and 25.5 mL/kg in Group A and B, respectively, significantly less than normal (41.8 mL/kg). The maximum expiratory flow at 25% FVC (MEF25) at 6 months of age was 6.9 and 8.1 mL.kg-1.s-1 in Group A and B, respectively, (predicted value, 39.2 mL.kg-1.s-1). FVC reached the normal range by 12 months of age in Group A, but remained lower until 36 months of age in Group B. MEF25 gradually increased in Group A, reaching 18.0 mL.kg-1.s-1 at 36 months of age, whereas in Group B it was severely decreased at the same age (3.5 mL.kg-1.s-1). More than 75% of the patients had airway hyperreactivity at all ages. We have demonstrated that in patients with moderate to severe BPD, vital capacity is moderately decreased, but catches up to normal levels by 36 months of age. In contrast, severe lower airway obstruction persists in all infants, although in those with moderate BPD gradual improvement is seen. These findings suggest that in BPD neither obstruction of the smaller intrathoracic airways nor bronchial hyperreactivity resolves during the first 3 years of life.

Bronchial Hyperreactivity↗