Mesocolonic lymphangioma: a case report with immunoperoxidase and electron microscopic studies. A 14 yr old girl presented with a large cystic mass in the transverse mesocolon which was completely excised. Cystic lymphangioma was diagnosed, based on the specific histologic, immunoperoxidase and ultrastructural findings.


Ki67 immunohistochemical evaluation in colorectal cancer and normal colonic mucosa. Possible clinical applications. Cell proliferation was evaluated by Ki67 monoclonal antibody in 33 colorectal adenocarcinomas and in the normal colonic mucosa. Immunoreactivity was assessed independently by two observers in two subsequent evaluations with a semiquantitative method, by counting at least 2000 cells in two distinct neoplastic specimens (central and peripheric section). There was an excellent intra-inter observer agreement in Ki67 score for each specimen. The tumor score range from 7 to 70% (median 48.8), without any significant correlation with sex and age of the patient and location, size, staging and grading of the neoplasm. Tumor Ki67 score was almost identical in central (46.96%) and in peripheral section (49.24%), and always higher than in normal mucosa. There was no distinction in Ki67 score in normal mucosa at various distances from the tumor. In our experience, Ki67 provides a reliable and reproducible method for assessment of proliferative activity; its clinical applications need further studies.


[Prognostic value of cellular ploidy in adenocarcinoma of the middle rectum]. A retrospective study of DNA content in 38 medium-rectal adenocarcinomas (a rectal part between 8 and 12 cm. from anus) was performed using flow cytometry in order to find probable correlations among ploidy, grading, staging and survival in patients who had undergone a surgical operation from January 1975 to December 1989. At the beginning of the work, 21 patients were alive and 17 were dead. Histologically 15 carcinomas (39.4%) were G1, 22 (57.8%) were G2 and only 1 (2.6%) was G3. Moreover 1 case (2.6%) was pT1, 7 (18.4%) were pT2 and 30 (78.9%) were pT3. 11 adenocarcinomas (29%) were euploid and 27 (71%) were aneuploid. These percentages agree with literature data. 11 of dead patients (64.7%) had aneuploid neoplasias and 6 (35.3%) diploid; 16 of alive patients (72.2%) had aneuploid carcinomas and 5 (23.8%) diploid. The difference of survival between aneuploid and diploid carcinomas isn't statistically significative (X2 = 0.168 ns). No correlation was found among aneuploidy, grading and staging, probably on account of small number of analyzed cases, owing to particular and little rectal part included in the study. Likely, having a larger case number we'll be able to obtain more incisive informations from this type of analysis in the next future.


[Chronic calculous cholecystitis: elementary and dysplastic lesions, echographic correlations and immunohistochemical approach]. The morphological analysis of 223 cases of chronic calculous cholecystitis has drawn attention to the following outstanding facts: (a) elementary lesions are numerous (above all ulceration, mucosal erosion, antral and intestinal metaplasia) and put together a complex sight; (b) mild, moderate and severe dysplasias have a surprising high incidence (67%), even in the age-group under 40; (c) dysplasia is more common in the gallbladders bearing parallel hyperplastic and metaplastic mucosal changes, if compared with gallbladders where these changes are lacking; (d) thickness of gallbladder's wall and incidence of dysplasia are in direct relation; (e) echographic preoperative assessment of wall's thickness has predictive value for presence of dysplasia; (f) CEA and CA 19-9 have a progressively increasing expression in the various degrees of dysplasia.


Morphology of non A-non B hepatitis (HNANB). A study of 104 cases. A series of 104 liver biopsies from patients with clinical HNANB were classified under code into established histologic groups. Activity and basic features were semiquantitatively assessed using a score system. In 23/104 cases non viral lesions were diagnosed. After breaking the code the remaining 81 hepatic biopsies were ranged into three groups: post-transfusional cases (PT) (n. 20), sporadic cases with clinically documented initial "acute hepatitis" (SP1) (n. 44), sporadic cases without determined onset of disease (SP2) (n. 17). There were no statistically significant features discriminating histologically PT group from SP 1 + 2 group. However, aggressive forms of hepatitis (acute hepatitis with piecemeal necrosis [AVH+PMN] and chronic aggressive hepatitis [CAH]) were more frequent in PT group (11/20 = 55% in PT versus 28/61 = 45.9% in SP 1+2 groups). No statistical significant differences were detected for the scored basic pattern (i.e. acidophilic body type, mononucleosis-like bead file pattern, etc.). Bile duct lesions were observed approximately with the same frequency in PT and SP1 groups. Prevalence of fatty change was striking: 55% in PT group and 54.1% in SP1 group.


[Pheochromocytoma and catecholamine cardiomyopathy]. We describe a 40 years old patient deceased of pheochromocytoma-caused heart failure, with no previous specific symptomatology. At autopsy the heart was characterised by thin cardiac walls and cavity dilatation. Histologic pattern showed extensive myocardial fibrosis and some acute myocytolytic areas. This pattern is equal to that of prolonged and decompensated stress cardiomyopathy. These pathologic pictures are both caused by catecholamines cardiotoxicity.


Immunocytochemical detection of megakaryocytes by endothelial markers: a comparative study. By endothelial markers such as FVIII, UEA-I, CD31 and QBEND/10, the Authors have investigated the immunohistochemical pattern of bone marrow megakaryocytes in myelodysplastic (8 cases) and myeloproliferative (35 cases) disorders as well as in control biopsies (8 cases). An evident cytoplasmic positivity with FVIII and UEA-I was encountered in all normal and pathological specimens, whereas the immunolocalization of CD31 was limited to megakaryocytes present in normal bone marrow biopsies or in cases of myelofibrosis. No immunostaining with QBEND/10 was observed in any case, although the most selective staining of endothelial cells of bone marrow vessels was noted with this antibody. The usefulness to utilize endothelial markers in order to identify atypical and immature forms of megakaryocytes as well as micromegakaryocytes, especially in myelofibrosis by the aid of CD31, was also discussed.


Risk factors for developing wheezing and asthma in childhood. Wheezing lower respiratory tract illness in infancy and asthma share the clinical findings of wheezing and respiratory distress. Although the link between wheezing lower respiratory tract illness in infancy and the subsequent development of asthma is a limited one, both conditions do share some common risk factors, including exposure to environmental tobacco smoke, difficult living conditions (low socioeconomic class, crowding, allergen exposure), and increased risk in males. The impact of baseline lung function on wheezing lower respiratory tract illness risk is substantial and may be independent of airway reactivity. In contrast, the development of chronic airway inflammation mediated by allergic sensitization plays a central role in the development of persistent asthma. Although the endogenous risks for these two outcomes may be fixed, it is clear that caregivers may help to reduce or eliminate the exogenous risks listed earlier by parental education and improvement of the living conditions of young children.


[Chondrosarcoma of the hyoid bone. Follow-up and cytological study of a case]. The follow-up study of one chondrosarcoma of the hyoid bone is reported; the tumor was a well differentiated grade II chondrosarcoma that relapsed after 10 months and metastasized after 6 years. Fine needle aspiration cytologic method was utilized for the diagnosis of the lung metastases. Cytologic criteria in the differential diagnosis of the chondrosarcoma are discussed. Follow-up of the extra-skeleton chondrosarcoma has to be continued for a long time independently from the grade of differentiation.


Asthma pathogenesis and the implications for therapy in children. Gaining greater insight into the pathogenesis of asthma has redefined the approach to treatment of children with asthma. Clearly, the Expert Panel of the National Heart, Lung, and Blood Institute National Education Program has played a major role in taking the message to a wide audience of health care providers. Although only early trends are evident at this point in time, within several years therapeutic trends underway currently will be more commonplace, and we may observe how asthma continues to impact society and our health care system. The approach to therapy will continue to evolve and most likely be controversial for years to come.


Crisis in asthma care.

Crisis in asthma care. Reports of increases in both hospitalizations and deaths due to asthma have provided a sense of crisis in asthma care. This article examines issues concerning this sense of crisis. The authors review current trends in prevalence, morbidity, hospitalization, and mortality from asthma and examine possible reasons for changes that have occurred. A review of data suggesting that asthma can result in irreversible, chronic airway obstruction is presented. Finally, the authors discuss the role of the primary care physician in the management of asthma.


Pediatric pulmonary function testing in asthma. Pulmonary function testing is an important tool in the management of asthma. Lung function can be readily assessed in both the office and patient's home. This article reviews spirometry, peak flow meters, and bronchial challenge testing. Their interpretation and clinical use are presented as well.


The impact of respiratory infections on asthma. It is apparent that the effects of viral respiratory infections on the development of airway hyperresponsiveness are multiple and interrelated and involved the production of viral specific IgE, upregulation of leukocyte inflammatory activity, enhancement of the factors involved in the generation of late phase allergic responses, altered beta-adrenergic and cholinergic nervous system activity, and damage to the airway epithelium. The summation of these effects is the development of airway inflammation rather than a direct effect on bronchial smooth muscle, per se. An understanding of this pathogenesis underscores the relative importance of anti-inflammatory rather than antimicrobial therapy in viral-induced exacerbations in asthma symptoms.


Allergens and asthma.

Allergens and asthma. This article presents the studies that show that asthma in children is strongly associated with sensitization to dust mite and other indoor allergens. In addition, the recent evidence that this association reflects a causal relationship between allergen exposure and asthma is reviewed. The relevance of quantitative measurements of the major indoor allergens (dust mite, cockroach, and cat) in the houses of children with asthma is discussed. Finally, the increasing evidence that avoidance measures can be an effective treatment for asthma is considered together with the details about avoidance protocol for dust mite and cat allergen.


Management of acute asthma.

Management of acute asthma. Patients with acute asthma experience increased airway obstruction, increased work of breathing, and ventilation-perfusion mismatch. Careful observation and assessment of the patient are fundamental for successful treatment. Therapy is dictated by the severity of the acute episode. Prevention of subsequent flares of asthma needs to be initiated as the patient convalesces.


Complicating features of asthma.

Complicating features of asthma. The recognition of factors other than asthma that make asthma worse, are confused with asthma, or occur concurrently with asthma and may or may not interact with asthma is as important as dealing with the asthma itself. In this article I have tried to give an overview of some of these factors: what they are, how they affect patients with asthma, and what to do about them. The recognition of a covert chronic sinusitis, for example, is often key to controlling a person's disease when it appears that everything is being done appropriately. Close attention to these factors will increase the success of treatment of asthma and improve the quality of life of patients.


Patient education.

Patient education. Only recently has it been appreciated that the considerable morbidity of asthma can be reduced with tools readily available to every physician who treats children. The pharmacotherapeutic armamentarium has been strengthened by better understanding of the pathogenesis of asthma, the impact of inflammation, and the role of preventive therapy. The task remains to put this expanded knowledge to use to help a larger number of children with asthma and their families to diminish the impact that the disease has on their lives. Concomitant with increased understanding of the pathophysiology of asthma and the medications used to control the process has been a greater appreciation of the role of co-management or self-management. Several programs have been developed to help parents and children with asthma gain better control over the disease, thus decreasing morbidity and significantly improving quality of life. These programs are available to physicians and health care organizations, and it is strongly recommended that asthma education, both as a formal course and in the physician's office, be regularly incorporated into the care plan for every child with asthma.


Is asthma curable?

Is asthma curable? The information reviewed here supports the concept that asthma is potentially curable. Reports of complete, durable remission of asthma can no longer be regarded as fortuitous occurrences, unrepresentative of asthma in general. Systematic studies of anti-inflammatory drug therapy designed to explore possible induction or remission of asthma clearly are warranted. Studies of aggressive anti-inflammatory drug therapy of asthma at the onset, to avoid establishment of chronic asthma, also are desirable. The current goals of therapy of asthma have been revised to include reduction of airway hyperreactivity with topical anti-inflammatory drugs, in addition to relief of current symptoms. This approach may provide valuable resistance to exacerbations in response to antigen exposures, infections, exercise, or irritants. Pathophysiologic mechanisms apparently essential to the establishment and perpetuation of chronic asthma have been identified. These processes may be vulnerable to eradication by combination therapy with existing pharmacologic agents such as cyclosporin A or FK-506 (to suppress cytokine production), gold, methotrexate, and other anti-inflammatory drugs, alone or in combination. Equally important, the vigorous anti-inflammatory therapy may be necessary only long enough to achieve a resolution of the chronic pulmonary inflammation. Systematic studies of the use of these agents to induce partial, or complete, stable remissions of asthma should be performed. In the past, remissions of asthma in children with neoplasia and the other patients presented herein were complete, durable, and welcome, but they were largely unexpected and unpredictable. For the future, there is increasing reason to believe that predictable pharmacologically induced remission of asthma will be feasible.


Branhamella catarrhalis colonization in preschool asthmatics. Branhamella catarrhalis has been associated with exacerbations of chronic bronchitis and asthma in adults. To investigate the possible role of B. catarrhalis in asthma of early childhood, we took posterior pharyngeal swabs from 24 normal children, 20 well asthmatics, and 20 acutely wheezy asthmatics, all between 1 and 4 years of age. On culture, 33% of the normal children were colonized with B. catarrhalis; colonization rates in the well asthmatics (70%) and in the wheezy asthmatics (75%) were significantly higher than in normals. The nature of this association requires further study.


Spontaneous desaturations in intubated very low birth weight infants with acute and chronic lung disease. Patients with chronic lung disease (CLD) have frequent episodes of spontaneous desaturations. Utilizing computerized pulse oximetry (CPO) we quantified the frequency and severity of spontaneous desaturations in very low birth weight (VLBW) infants with CLD. Thirty-four studies by CPO were performed in intubated infants for 4 hours; 17 patients (birth weight, 550-980 g; postnatal age 28-85 days) had CLD, and 17 (birth weight, 520-980 g; postnatal age, 1-7 days) had acute lung disease. Oxygen saturation (SaO2) was measured with the Nellcor N-200 oximeter, its serial output (updated once a second) captured by a computer. Pulse rate, pulse amplitude, and heart rate were also monitored continuously. We measured respiratory system mechanics in 23 patients. Tidal volume (VT), respiratory system compliance (Crs), and resistance (Rrs) were obtained by the PeDS system. Spontaneous desaturation to SaO2 less than 90% occurred for 4.5% of the time in acute patients vs. 27.1% of the time in chronic patients (P less than 0.0001); to SaO2 less than 85%, 0.7% vs. 7.6% of the time in acute vs. chronic patients (P less than 0.002); and to SaO2 less than 80%, 0.4% vs. 2.6% of the time in acute vs. CLD patients (P less than 0.05). Rrs was significantly higher in the ventilated patients with CLD (174 cmH2O/L/s) than in the ventilated patients with acute lung disease (94 cmH2O/L/s, P less than 0.0001). The mean Crs values of the two groups were comparable. Our preliminary data indicate that VLBW infants with CLD receiving assisted ventilation have a greater number of spontaneous desaturation episodes, as compared to patients with acute lung disease.


Intensive care course and outcome of patients infected with respiratory syncytial virus. PICU admissions of 97 children positive for respiratory syncytial virus on fluorescent antibody screening were reviewed; 68% of 44 patients without history of preceding disease (Group I) and 79% of 53 patients with preceding pulmonary, cardiac, or other disease (Group II) required ventilation. In Group I ventilated children weighted significantly less (P = 0.001) and were of lower chronological (P = 0.02) and post-conceptional ages (P = 0.02) than those not ventilated. Eighteen infants ventilated for apnea weighted significantly less (P = 0.003), were more often born at less than or equal to 37 weeks gestation (P = 0.001) and were at lower post-conceptional age than 11 infants ventilated for progressive respiratory deterioration. There was no significant difference in mean weight, chronological age, post-conceptional age, CO2, or pH between 12 admissions with BPD who required ventilation for RSV infection and 5 who did not require ventilation. Ribavirin administration to five ventilated patients with BPD did not significantly alter the duration of intubation of PICU stay. Six patients with cardiac disease required longer periods of ventilation than others (Group I, P = 0.001; all others in Group II, P = 0.04). No deaths occurred in Group I, while 6 of 53 (11%) patients in Group II died. In this series immuno compromise placed patients at greatest risk of dying. Mechanical ventilation can be safely managed in previously healthy, RSV infected infants and should be initiated before significant cardiorespiratory compromise arises.


Prolonged apnea and oxyhemoglobin desaturation in asymptomatic premature infants. Seventy-eight longitudinal four-channel recordings of heart rate, thoracic impedance, nasal thermistry, and pulse oximetry were performed on 26 asymptomatic premature infants (gestational age, 29.9 +/- 1.58 weeks; birth weight, 1,753 +/- 226 grams; postconceptional age, 34.3 +/- 2.0 weeks; postnatal age, 4.41 +/- 2.40 weeks; all values mean +/- SD). Tracings were scored for central and obstructive apnea, bradycardia, periodic breathing, apnea density, and prolonged apnea. The studies demonstrated 585 episodes (7.41/recording) of oxyhemoglobin desaturation with less than 90%. Recordings had a mean of 16.1 episodes of central apnea, 3.04 episodes of obstructive apnea, and 2.34 episodes of bradycardia. Periodic breathing and short obstructive apneas correlated significantly with the total number of oxyhemoglobin desaturations of less than 80% and 90%. Episodes of prolonged apnea were seen in 20 of 78 recordings. In the latter a significantly higher number of total desaturations (less than 90%), desaturations less than 80% and 90% in association with apnea and with bradycardia, longer desaturations, desaturations during sleep, and isolated bradycardia were observed. Variations in heart rate, thoracic impedance, nasal air flow, and pulse oximetry are associated with episodes of oxyhemoglobin desaturation in asymptomatic premature infants. These infants, although asymptomatic, may be at risk for impaired tissue oxygenation.


Gas exchange during exercise in diabetic children. The purpose of this study was to evaluate the cardiorespiratory and metabolic response to exercise in 33 children, aged 9 to 15 years, affected by type I diabetes mellitus, in comparison with 47 age-, sex-, weight-, and height-matched healthy children. All diabetic children were on a mixed split-dose insulin regimen, consisting of both regular and long-acting insulin in the morning and evening. The last insulin injection was administered on average 6 hours before the test. The mean duration of diabetes mellitus was 5.0 +/- 3.1 years. The metabolic control was evaluated on the basis of HbA1 levels (mean, 8.9 +/- 1.8%). Pulmonary function tests and progressive exercise tests on the treadmill were performed. Gas exchange, ventilation, and heart rate (HR) were monitored during the tests. The O2 pulse (VO2/HR) was calculated. There was no difference in the baseline oxygen uptake (VO2) between the diabetic children and the control group. VO2 peak was significantly lower (P less than 0.01) in the diabetic adolescents (41.2 +/- 5.9 mL/min/kg) compared to control subjects (46.3 +/- 9.6 mL/min/kg) and it was achieved at an earlier (P less than 0.01) time of run (7.5 +/- 1.8 vs. 9.1 +/- 2.8 min). Anaerobic threshold and minute ventilation were similar in the two groups. The O2 pulse throughout the test was significantly lower (ANOVA, P less than 0.001) in the diabetic group compared to the controls. No differences were found in resting and post-exercise spirometric values. In conclusion, our study shows that well-controlled diabetic adolescents have a reduced working capacity.(ABSTRACT TRUNCATED AT 250 WORDS)


Evaluation of the multiple linear regression method to monitor respiratory mechanics in ventilated neonates and young children. A potentially useful method to monitor respiratory mechanics in artificially ventilated patients consists of analyzing the relationship between tracheal pressure (P), lung volume (V), and gas flow (V) by multiple linear regression (MLR) using a suitable model. Contrary to other methods, it does not require any particular flow waveform and, therefore, may be used with any ventilator. This approach was evaluated in three neonates and seven young children admitted into an intensive care unit for respiratory disorders of various etiologies. P and V were measured and digitized at a sampling rate of 40 Hz for periods of 20-48 s. After correction of P for the non-linear resistance of the endotracheal tube, the data were first analyzed with the usual linear monoalveolar model: P = PO + E.V + R.V where E and R are total respiratory elastance and resistance, and PO is the static recoil pressure at end-expiration. A good fit of the model to the data was seen in five of ten children. PO, E, and R were reproducible within cycles, and consistent with the patient's age and condition; the data obtained with two ventilatory modes were highly correlated. In the five instances in which the simple model did not fit the data well, they were reanalyzed with more sophisticated models allowing for mechanical non-homogeneity or for non-linearity of R or E. While several models substantially improved the fit, physiologically meaningful results were only obtained when R was allowed to change with lung volume. We conclude that the MLR method is adequate to monitor respiratory mechanics, even when the usual model is inadequate.


Apnea and periodic breathing in healthy full-term infants, 12-18 months of age. Many children older than 12 months of age are now on home monitors. Home pneumograms performed on normal infants have established standards, and have been used to evaluate infants during their first year. However, no standards have been described for infants older than 12 months. We, therefore, recorded the standard pneumogram on 88 full-term healthy infants who were 12-18 months of age. We analyzed the recordings for average respiratory and heart rates, apnea (greater than or equal to 6 seconds) density, longest apnea, periodic breathing, and bradycardia for 12 hours. We compared the values in males vs. females and in infants 12-14.9 months vs. 15.0-18.0 months of age. Since there was no difference in any parameter measured in any group, we combined the values to determine the normal values for this population.


Delivery of micronized budesonide suspension by metered dose inhaler and jet nebulizer into a neonatal ventilator circuit. We compared the delivery of a micronized suspension of budesonide by a metered dose inhaler (MDI) with two different spacers (Aerochamber and Aerovent) and by two jet nebulizers (MAD2 and Ultravent) to a ventilated neonatal test-lung using a standard neonatal ventilator circuit. The combination of MDI and Aerochamber was significantly better at delivering budesonide to a filter in front of the test lung (14.2% of aerosolized dose) than were either the MDI and Aerovent (3.6%) or the Ultravent or MAD2 jet nebulizers (0.02% and 0.68% of initial reservoir dose). Of the droplets emerging from the MDI, Aerochamber, and ET tube, 18% of the initial dose was in droplets less than 4.7 microns. Assuming that the test-lung model accurately reflects in vivo deposition, the combination of MDI and Aerochamber appears to be an extremely effective way of delivering budesonide aerosol to ventilated newborn infants.


Lung mechanics and gas exchange in ventilated preterm infants during treatment of hyaline membrane disease with multiple doses of artificial surfactant (Exosurf). Eight premature infants ventilated for hyaline membrane disease and enrolled in the OSIRIS surfactant trial were studied. Lung mechanics, gas exchange [PaCO2, arterial/alveolar PO2 ratio (a/A ratio)], and ventilator settings were determined 20 minutes before and 20 minutes after the end of Exosurf instillation, and subsequently at 12-24 hour intervals. Respiratory system compliance (Crs) and resistance (Rrs) were measured by means of the single breath occlusion method. After surfactant instillation there were no significant immediate changes in PaCO2 (36 vs. 37 mmHg), a/A ratio (0.23 vs. 0.20), Crs (0.32 vs. 0.31 mL/cm H2O/kg), and Rrs (0.11 vs. 0.16 cmH2O/mL/s) (pooled data of 18 measurement pairs). During the clinical course, mean a/A ratio improved significantly each time from 0.17 (time 0) to 0.29 (time 12-13 hours), to 0.39 (time 24-36 hours) and to 0.60 (time 48-61 hours), although mean airway pressure was reduced substantially. Mean Crs increased significantly from 0.28 mL/cmH2O/kg (time 0) to 0.38 (time 12-13 hours), to 0.37 (time 24-38 hours), and to 0.52 (time 48-61 hours), whereas mean Rrs increased from 0.10 cm H2O/mL/s (time 0) to 0.11 (time 12-13 hours), to 0.13 (time 24-36 hours) and to (time 48-61 hours) with no overall significance. A highly significant correlation was found between Crs and a/A ratio (r = 0.698, P less than 0.001). We conclude that Exosurf does not induce immediate changes in oxygenation as does the instillation of (modified) natural surfactant preparations. However, after 12 and 24 hours of treatment oxygenation and Crs improve significantly.(ABSTRACT TRUNCATED AT 250 WORDS)


Exosurf treatment investigational new drug phase: effect of an individualized third dose in infants with respiratory distress syndrome. Of 95 infants treated with the synthetic surfactant, Exosurf, under a Treatment Investigational New Drug protocol, 17 received one dose, 40 received two, and 38 received three doses. Seventy-six (80%) of the infants were treated by rescue protocol. We retrospectively reviewed the clinical course of the 67 surviving rescue infants. We found that, compared to one- and two-dose infants, those treated with three doses of Exosurf were more premature, smaller, required a longer ventilator course, and had more frequent complications, including patent ductus arteriosus (PDA), intraventricular hemorrhage, nosocomial pneumonia, and apnea. They required higher oxygen concentrations starting 8 hr after their first dose and higher mean airway pressure (MAP) from the time of their second dose. These trends continued during all subsequent time points, as compared to infants treated with two doses. The third dose was administered an average of 17 hr after the second, resulting in little change of MAP, but some reduction in oxygen requirements. By 24 hr after the last dose, only 4% of three-dose infants were extubated compared with 30% of the two-dose and 71% of one-dose infants. In conclusion, repeated administration of Exosurf is not equally effective in every treated infant with respiratory distress syndrome (RDS) and complications of prematurity may affect or accompany poor response.(ABSTRACT TRUNCATED AT 250 WORDS)


Spirometric and endoscopic evaluation of airway collapse in infants with bronchopulmonary dysplasia. We evaluated eight infants with bronchopulmonary dysplasia (BPD) at ages from 2 to 13 months who had repeated episodes of clinical respiratory deterioration associated with agitation. These episodes limited further weaning from ventilation or necessitated recurrent intubation and reinstitution of ventilation. All infants underwent spirometric evaluation and six also had endoscopic examination during simulated agitation episodes (elicited by toe pinching). All babies were found to have a very prolonged near zero expiratory airflow pattern, accompanied by vigorous diaphragmatic and abdominal muscle activity and rapid development of hypoxia. Six patients had endoscopically documented tracheal collapse under the same simulated circumstances. The episodes ceased with calming or sedation of the infants.


The in vitro effect of triamcinolone acetonide on branching morphogenesis in the fetal rat lung. We have studied the effect of triamcinolone acetonide (TAC) on airway morphogenesis of the Sprague-Dawley fetal rat in whole organ lung cultures from day 15 to day 21 of equivalent gestational age (6 days in culture). TAC produced an increased number of peripheral buds from day 18 onward and the airway and airspaces had larger lumens. Airway branching was increased compared to controls, and there was a higher proportion of airway epithelium and a lower proportion of mesenchyme. Cell height was significantly lower in TAC treated lungs except on day 17. This was due to accumulation of glycogen prior to the increased branching activity. In both controls and TAC-treated lungs, peripheral bud number and volume proportion of epithelium increased with time in culture, whereas volume proportion of mesenchyme, mean chord length of airways and airspaces, and epithelial cell height decreased. These changes were more pronounced in the TAC-treated group and were significant. However, TAC-treated lungs were morphologically irregular. We conclude that TAC has a direct effect on airway morphogenesis and it promotes growth of morphologically abnormal lungs. TAC also appears to enhance airway branching and morphologic changes interpreted as increased epithelial maturation.


A prospective trial using salivary-theophylline levels to guide asthma therapy. In three prospectively designed studies, first saliva (SA) samples were collected simultaneously with serum (SE) from 86 children who received slow-release theophylline (Th) b.i.d. for treatment of bronchial asthma. SA was collected with a standardized sampling procedure. Regression analysis revealed a close correlation between SE and SA-Th levels (r = 0.959; SE = 1.87 x SA + 0.05) and yielded a "therapeutic SA-Th range" of 5.8 to 10.7 mg/L. In 16 children the diurnal variation was then assessed by measuring 6 SA-Th levels within 24 hr, using the same sampling method. At 0, 9, and 24 hr SE-Th levels were also measured. The levels of SE-Th and SA-Th were again closely correlated (0.914 less than or equal to r less than or equal to 0.949) and both remained constant over the 24-hr period. In the third prospective trial only SA levels were used to monitor Th therapy in 50 asthmatic children. Seven days after starting therapy SA-Th levels were measured and then the Th dose was increased weekly until SA-Th levels above 5.8 mg/L were reached. The following day SE and SA samples were collected simultaneously and their Th levels compared. In 36 of the 47 children who completed the study therapeutic SE-Th levels (greater than or equal to 10 and less than or equal to 20 mg/L) were measured; in one patient it was greater than or equal to 20 mg/L, in 6 it was between 8.0 and 10 mg/L, and only 4 had SE levels less than 8.0 mg/L.(ABSTRACT TRUNCATED AT 250 WORDS)


Early treatment of respiratory distress syndrome with bovine surfactant in very preterm infants: a multicenter controlled clinical trial. To determine the effect of bovine surfactant (SF-RI 1, Alveofact) administered during the first hour following birth to very premature infants [gestational age (GA), 25-30 weeks] in a multicenter, controlled trial. Survival without bronchopulmonary dysplasia (BPD; definition: ventilator dependency or FiO2 greater than 0.3 during spontaneous respiration) at day 28 is increased in surfactant-treated infants (sequential analysis). Thirty-four infants [GA 28.0 +/- 1.5 SD weeks, birth weight (BW), 1,048 +/- 299 g] received 50 mg/kg BW surfactant, whereas 35 infants (GA, 27.6 +/- 1.5 weeks, BW 969 +/- 269 g) served as controls. Retreatment with surfactant (up to three identical doses) 12-24 hours after the previous dose was permitted if FiO2 was greater than 0.5. Survival without BPD was significantly higher in surfactant treated infants (26/34) compared to controls (14/35; P = 0.003), but in the incidence of pulmonary air leaks, patent ductus arteriosus, intracranial hemorrhage, and nosocomial infections they were not different. Bovine surfactant treatment improves survival without BPD in very premature infants at risk for neonatal respiratory distress syndrome (RDS).


IgG subclass antibody responses to alginate from Pseudomonas aeruginosa in patients with cystic fibrosis and chronic P. aeruginosa infection. Chronic bronchopulmonary infection with alginate-producing, mucoid Pseudomonas aeruginosa is characteristically associated with cystic fibrosis (CF). A significant correlation between the antibody response to alginate and poor lung function has been reported. Enzyme-linked immunosorbent assays were developed for the quantitation of human IgG1, IgG2, IgG3, and IgG4 antibodies to P. aeruginosa alginate. We investigated the pattern of IgG subclass antibodies against P. aeruginosa alginate in serum of patients with CF, others with chronic P. aeruginosa infection, and healthy controls. Healthy controls and patients with CF, before they acquired P. aeruginosa infection, had no or very low titers of antibodies against P. aeruginosa alginate. The latter with chronic infection had significantly higher antibody levels than all others groups, including patients with chronic P. aeruginosa infection but no CF. CF with chronic P. aeruginosa infection led to an inverse correlation between lung function parameters and levels of IgG3 and IgG4. Fifty-seven patients with CF have been followed for an average of 12 years with multiple antibody assays covering the preinfection, early, and late stage of chronic infection. All of them developed IgG1 and IgG3 antibodies to alginate at the start of infection. IgG2 antibodies developed later and showed only a slow increase during the chronic infection. Patients who died had significantly higher IgG2 anti-alginate antibody levels than other investigated groups. Elevated levels of IgG2 and IgG3 antibodies to P. aeruginosa alginate are a sign of poor prognosis in CF.


Response to inhaled bronchodilators and nonspecific airway hyperreactivity in children with cystic fibrosis. We tested the hypothesis that children with CF who have a significant response to bronchodilator (BD) would respond positively to standard methacholine (Mch) challenge. Our objective was to correlate the response to BD with the concentration that produced a 20% fall (PC20) in forced expiratory volume in 1 second (FEV1). We studied 22 patients (12 males), aged 10.5 +/- 0.7 years (mean +/- SE), with a Shwachman-Kulczycki score 82 +/- 2.6 and baseline FEV1 of 80 +/- 4.5% predicted. Baseline expiratory flows, static lung volumes, and airway resistance were measured before and 30 min after inhaled salbutamol. On a separate day, within 2 weeks, a Mch challenge was given, with doubling concentrations from 0.03 to 8.0 mg/mL. A positive challenge was defined as a PC20 less than or equal to 2.0 mg/mL, and a positive response to BD as a greater than 6% of FEV1 increase. Mch challenge yielded 17 responders (R) with a PC20 of 0.5 +/- 0.1 mg/mL, and 5 nonresponders (NR) with a PC20 of 8.8 +/- 2.9 mg/mL. Baseline FEV1 was 77 +/- 5.3% predicted in R compared to 89 +/- 6.3% in NR (P = less than 0.001). History of springtime rhinitis was positive in 9/17 R and 2/5 NR. No significant correlation was found between baseline FEV1 and PC20, or between change in FEV1 post-BD and PC20. A greater than 6% increase in FEV1 was seen in 14/17 R (83% sensitivity) and in none of the 5 NR (100% specificity). In R, 8/17 patients had baseline FEV1 less than 80% predicted, compared to 1/5 in NR.(ABSTRACT TRUNCATED AT 250 WORDS)


Soluble interleukin-2 receptor levels in infants with bronchopulmonary dysplasia. Soluble interleukin-2 receptors (sIL2R) in plasma have been identified as a marker of lymphocyte activation. Lymphocyte activation as a manifestation of inflammation may be important in the pathogenesis of bronchopulmonary dysplasia (BPD). To test the hypothesis that infants with BPD have higher sIL2R levels, 12 infants with or at risk of developing BPD (GA +/- SD, 27 +/- 5 weeks; BW +/- SD 1,053 +/- 733 g) had plasma sIL2R levels determined and were compared to 20 infants being ventilated for respiratory distress syndrome (RDS) (GA +/- SD, 28 +/- 3.5 weeks; BW +/- SD, 1,133 +/- 390 g: P = NS for both GA and BW, t test). Tracheal aspirates in both groups were also analyzed for sIL2R levels. To control for the effects of postnatal age (PNA) and study weight (SW) on the sIL2R levels, another group of 16 nonventilated babies (NVB) had plasma analyzed for sIL2R (PNA +/- SD: 39 +/- 40 days NVB vs. 48 +/- 36 days BPD; P = NS); (SW +/- SD: 1391 +/- 250 g NVB vs. 1212 +/- 700 g BPD; P = NS). The following data were obtained for the plasma sIL2R levels (mean +/- SEM U/mL): RDS controls, 1,231 +/- 80; BPD infants, 1,790 +/- 120; NVB controls, 1,319 +/- 76; P = 0.0005 RDS vs. BPD and P = 0.002 BPD vs. NVB. There was no significant difference in the sIL2R levels for the infants at risk of developing BPD vs. the infants with established BPD. Also, when analyzed separately, infants at risk of BPD and the infants with established BPD had higher sIL2R levels than the RDS and NVB controls. No differences were noted in the tracheal sIL2R levels in the BPD vs. RDS groups. These data indicate that infants with BPD had significantly higher sIL2R levels in plasma than either RDS or NVB controls. Therefore, lymphocyte activation may play a role in the pathogenesis of BPD.


Adaptive control of inspired oxygen delivery to the neonate. Adaptive adjustment of inspired oxygen (FIO2), based on a desired percent arterial hemoglobin saturation (SO2) was achieved by on-line bedside control of the oxygen concentration delivered to the neonate. Fourteen infants with bronchopulmonary dysplasia (BW, 860 +/- 80 g; GA, 26 +/- 1 weeks; study age, 41 +/- 8 days) receiving oxygen-air mixtures by hood were studied. The desired range of SO2 from 92 to 96% with a target value of 95% was determined by pulse oximetry and maintained with adjustment of FIO2 using three modes: 1) standard neonatal intensive care protocol with oxygen delivery evaluated at 20 minutes intervals; 2) bedside manual control with FIO2 manipulation every 2 to 5 minutes; and 3) adaptive control with on-line adjustment of FIO2 according to a specifically designed adaptive program. Each study period was of 40 minute duration. SO2 values within a steady 94 to 96% range was achieved for 54% of the time with standard protocol, compared to 69% (P less than 0.01) with bedside manual control and 81% (P less than 0.01) with adaptive control. In addition, fluctuations in SO2 values and overshoots were less apparent with adaptive control of oxygen delivery. These data describe adaptive FIO2 control as an efficient alternative technique for achieving a stable desired range of oxygenation in neonates.


Respiratory compliance in infants--a preliminary evaluation of the multiple interrupter technique. Measurements of total respiratory system compliance (Crs) using the multiple occlusion technique (MOT) in spontaneously breathing infants can be difficult to interpret in the presence of an unstable end-expiratory level. Similarly, measurements using the passive flow volume technique (PFV) are invalidated if there is alinearity of the expiratory time constant (Trs), irrespective of respiratory effort. For possibly overcoming these problems, we assessed the feasibility of a technique using multiple interruptions of of a single expiration (MIT), obtaining several pairs of volume-pressure data, from one expiration, which relate to a single end-expiratory level. Crs was measured in 16 infants aged 0.5 to 20 months using the MOT, MIT, and PFV technique. The MOT and the MIT each failed in one (different) infant, both succeeding where the other failed. The PFV technique failed in five infants in whom no acceptable plateau of airway pressure during occlusion and no Trs could be obtained from a single breath. Failure to obtain a linear Trs was accompanied by failure of the MIT in only one infant. Individual differences between the MIT and the MOT were less than 9%. However, the PFV measurements varied from -16.3% and +25.7% of the values from MIT or MOT. The greatest differences between Crs values coincided with the greatest differences between volume intercepts of the extrapolated volume-pressure (MOT, MIT) and flow-volume (PFV) data. From this preliminary study, the MIT proved as successful as the MOT, requiring fewer occluded breaths to measure Crs. In infants with a rapid respiratory rate, the data from several expirations can be merged and analyzed as for the MOT.


Generalized lymphangiomatosis and chylothorax in the pediatric age group. Four patients with generalized lymphangiomatosis presenting with chylothoraces are described. All four had bone involvement, two had involvement of the spleen, and one of the pericardium. The diagnosis was confirmed by typical radiology, histology, and in three patients by immunohistochemistry. Treatment was mainly palliative. Three patients died within 1/2 to three years of presentation.


Transcutaneous blood gas monitoring during salbutamol inhalations in young children with acute asthmatic symptoms. The effect of salbutamol inhalations on transcutaneous blood gases was investigated in 23 children (aged 11 months-2.5 years) with asthmatic symptoms. After one salbutamol inhalation there was a mean increase in transcutaneous PO2 (tcPO2) of 0.5 kPa (P less than 0.01); after a second dose given 30 minutes later, the mean increase was 1.2 kPa (P less than 0.001). The increase in tcPO2 after only one dose of salbutamol was significantly correlated to age (P less than 0.01). No such correlation was observed after a second dose. The overall increase in tcPO2 after two salbutamol inhalations showed a negative correlation to the duration of the current symptomatic period (P less than 0.05). We conclude that salbutamol inhalations have beneficial effects in young children with acute asthmatic symptoms, even below the age of 18 months, provided that an adequate dose reaches the lung and preferably at an early stage of obstruction.


Transcutaneous and arterial blood gas monitoring during acute asthmatic symptoms in older children. The relationship between transcutaneous and arterial blood gases was investigated in 14 children with asthmatic symptoms, aged 7-15 years, before and after the inhalation of salbutamol. The degree of bronchial obstruction was assessed by forced expiratory volume in one second (FEV1) and maximum expiratory flow when 25% of FVC remained to be expelled (MEF25). On average the transcutaneous PO2 (tcPO2) was 1.3 kPa (range, 2.6-0 kPa) lower and the transcutaneous PCO2 was 0.6 kPa (range, 0-1.5 kPa) higher than the corresponding arterial values (P less than 0.01). The difference between arterial and transcutaneous PO2 was the same over the whole range of values studied (7.5-14 kPa). After the inhalation of salbutamol, the relationship between transcutaneous and arterial blood gases was not significantly changed. Changes in transcutaneous PO2 correlated to changes in MEF25 (P less than 0.05), indicating a common denominator, probably the conditions in the peripheral airways. We conclude that the close relationship between transcutaneous and arterial blood gases, even after the inhalation of a beta-2 agonist, indicates that the transcutaneous technique can be used for monitoring acute bronchial obstruction and for evaluating the effects of treatment in children of different ages.


Intratracheal administration of pulmonary vasodilator agents. We compared intravenous and intratracheal administration of histamine (0.4 and 1.6 micrograms/kg, respectively) and nitroglycerin (5.0 and 20.0 micrograms/kg, respectively) in seven hypoxemic 2 week old lambs, during right lung only perfusion, to see if intratracheal administration could limit their vasodilator action to the pulmonary vessels. The hemodynamic variables: pulmonary artery pressure (Ppa), left atrial pressure (Pla), pulmonary blood flow per kilogram (Q/kg), and aortic pressure (Pao) were measured at baseline and in each experimental state, then pulmonary vascular resistance (PVR) and systemic vascular input resistance (SVR) were determined. We found that intravenous histamine showed some pulmonary vasodilator selectivity in that it caused a 19% decrease of Ppa from baseline (P less than 0.002), a 23% decrease of PVR from baseline (P less than 0.002), and an 8% decrease of SVR from baseline (P less than 0.05). Intratracheal histamine produced smaller effects, decreasing Ppa by 11% from baseline (P less than 0.02), and PVR by 14% from baseline (P less than 0.02), while SVR was unaffected. Intravenous nitroglycerin decreased cardiac output by 16% from baseline (P less than 0.02), and also decreased SVR by 8% while producing a small increase in PVR. Intratracheal nitroglycerin caused a similar 17% (P less than 0.01) decrease in cardiac output, and again an increased PVR but a decreased SVR. This study confirms that histamine has some intrinsic pulmonary vasodilator selectivity. Furthermore, the data suggest that intratracheal administration may accentuate pulmonary selectivity by lessening systemic effects. Nitroglycerin, on the other hand, had untoward hemodynamic effects in the presence of hypoxia.


The relationship of nasal disorders to lower respiratory tract symptoms and illness in a random sample of children. We examined the relationship of nasal disorders, defined as frequent colds and sinus trouble, to lower respiratory tract symptoms in a random population of 718 children aged 4 to 11 years in East Boston, Massachusetts. Frequent colds were significantly associated with maternal smoking (odds ratio (OR) = 3.00; 95% confidence interval (CI) = 1.97, 4.58), and so was sinus trouble (OR = 4.73; 95% CI = 1.78, 12.51). After adjustment for maternal smoking, age and sex, frequent colds (OR = 2.88; 95% CI = 1.87, 4.42) and sinus trouble (OR = 4.95, 95% CI = 1.83, 13.39) remained significant predictors of lower respiratory tract symptoms in separate logistic regressions. If one restricted the cohort to the 513 children who also had personal smoking information and adjusted for this variable as well, the results for colds were unchanged (OR = 2.94; 95% CI = 1.78, 4.84) but the results for sinus trouble were now not statistically significant (OR = 2.30, 95% CI = 0.67, 7.94). We conclude that nasal disorders are associated with lower respiratory tract symptoms in children.


Collagen degradation during postnatal lung growth in rats. Postnatal lung growth involves remodeling of the structure seen at birth as new alveoli are formed. To determine the role of collagen degradation in this process, in particular of the basement membrane component, we studied the synthesis of total collagen and the degradation of collagen types I or IV in a series of rats from birth to 29 days of age. During the period of rapid cell proliferation to day 11, the collagen level per mg lung did not change though the rate of synthesis increased. Up to 40% of new collagen was rapidly degraded. At the end of the growth phase, the interstitium became thinner and less cellular. Collagen synthesis slowly decreased as the total collagen content increased in the lung, and less than 20% of newly synthesized collagen was degraded. Type I collagenase activity was highest during the cell proliferation phase, though less than 20% was due to active enzyme. In contrast, type IV collagen breakdown, also maximal in the first 11 days, was almost all due to enzymes present in the active form. The results demonstrate that rapid degradation of collagen, particularly the type IV form present in basement membranes, occurs during the early phase of postnatal lung growth.


Ovarian cysts in the fetus and neonate--changes in sonographic pattern in the follow-up and their management. In a multicenter trial we retrospectively evaluated the clinical and sonographic data of 49 neonatal ovarian cysts, 44 of which were detected prenatally and 5 on the first day after delivery. Of the 44 prenatally detected cysts 39 were purely cystic, 5 echogenic or had a mixed pattern. In 20 patients the cystic appearance changed during delivery from purely cystic to a mixed pattern being independent on the size of the cyst. 26 of the 44 cysts were treated surgically. Salpingotorsion was found in 8 and was independent on the size of the cyst. In 15 a salpingo-oophorectomy or oophorectomy was performed, in 11 the ovary was saved. 23 patients were followed sonographically: 15 cysts showed complete resolution within 14 months without correlation to the sonographic pattern. The volume of these cysts varied between 5 and 71 ml. Neonatal ovarian cysts disappear spontaneously frequently and rarely cause severe symptoms. The authors recommend follow-up by ultrasound as the primary modality. Surgical intervention is recommended only if the cyst is space-occupying and percutaneous puncture can not be performed or in the case of emergency.


Urinary tract infection in infants in spite of prenatal diagnosis of hydronephrosis. The efficacy of preventing neonatal urinary infection in infants by diagnosing hydronephrosis in the fetus on obstetrical ultrasonography was studied. 426 infants had uroradiologic evaluation between 1984 and June 1991 because they had hydronephrosis detected in utero. Thirteen with posterior urethral valves were excluded. Of the remaining 413, 13 (3.1%) presented with urinary infection in the first 6 months of life. Ten of the 13 were boys and 7 were not circumcised. Eleven of the 13 infants less than 2 months old were formula-fed. The causes of hydronephrosis were reflux alone in 6, ureteropelvic junction obstruction in 6 (with coexisting ipsilateral reflux in 4), and primary megaureter in 1. Ultrasonography alone was insufficient to exclude reflux. Amoxicillin-resistant bacteria were the causative organisms in all 10 for whom bacteriology data was available. Four categories of management failure were identified: 1) failure of communication of the prenatal findings, 2) antibiotics not prescribed, 3) antibiotics prescribed but not administered, and 4) infection in spite of continuous antibiotic prophylaxis. Uncircumcised formula-fed male infants with reflux seemed to be at special risk for infection.


Cerebral magnetic resonance imaging (MRI) of very low birth weight infants at one year of corrected age. Cerebral MRI was performed at 1.5 T in 27 infants with birth weight below 1500 grams at 1 year of corrected age. The images were compared to those reported on normal development at the same age. On T1 weighted images, 20 (74.1%) of the 27 infants showed myelin deposition different from what has been reported to be normal. Areas most affected were the central occipital white matter and the centrum semiovale. Both correspond to "watershed areas" known to be at risk for periventricular leukomalacia in preterm infants. T2-weighted images showed delayed myelination in the same areas as described for T1. In addition, two infants showed delayed myelination in the central occipital white matter and one in the centrum semiovale. Patchy focal abnormalities involving the white matter were seen in seven (25.9%) infants. Mild cerebral atrophy, mainly of the cortex was found in 10 (37.0%) infants. Irregular shape of the lateral ventricles, especially of the occipital horns was present in 12 infants (44.4%). 11 of these infants also had deviating changes in myelination. Only 2 infants (7.4%) had a normal MRI examination. Follow-up MRI examinations are needed to determine whether the high percentage of changes in myelination represent delayed development or brain damage in preterm infants.


Choroid plexus cysts: a normal finding on ultrasound. Within a period of 2.5 years, cystic structures in the choroid plexus were encountered at cerebral sonography in 70 neonates and babies (45 male, 25 female; 18 premature babies). Their prevalence in patients examined during the first 4 weeks of life (n = 55) was 3%. The size of the cysts ranged from 1-4 and, rarely, up to 7 mm. They were mostly solitary and unilateral. Follow-up sonograms over periods up to 13 months showed that most of the cysts persisted unchanged. A few disappeared (n = 7), while distinct increase in size was observed in 1 case. Since no additional sonographic changes were observed and none of the patients displayed any neurological abnormalities and no association existed with any other, particularly chromosomal, disease, such plexus cysts are postulated to represent a normal sonographic finding and do not require follow-up.


Symptomatic third ventricular choroid plexus cysts. We describe the imaging findings in 3 children with choroid plexus cysts (CPC) at the foramen of Monro. All CPC measured less than 2 cm and produced symptoms of raised intracranial pressure when located at the foramen of Monro where there was obstruction to the cerebrospinal fluid (CSF) flow. Among the imaging studies done on our patients, CPC were depicted best by cranial sonography and CT-ventriculography and missed by standard CT and MRI. Misdiagnosis can lead to inappropriate shunting with adverse effects. Two of our patients had relief of symptoms after resection of the cyst. One patient with inoperable cardiac defects died and had no surgery performed. Serial CT and sonographic studies in this patient showed progression in the size of the cyst and ventriculomegaly. Cranial sonography and CT-ventriculography are the modalities of choice in evaluating ventriculomegaly when the diagnosis of occult obstructive CPC is entertained in children. Cranial sonography is indicated in infants with an open fontanelle and CT-ventriculography is reserved for older children with hydrocephalus which is not responding to shunting.


Leptomeningeal cyst: early diagnosis by color Doppler imaging. A newborn with a leptomeningeal cyst over the anterior fontanelle due to birth trauma is described. Color Doppler flow sonograms were helpful to diagnose the leptomeningocele in its early stages and to differentiate it from a cephalhematoma or subgaleal haemorrhage by demonstrating cerebro-fugal flow in an arterial connection between the extracranial fluid collection and the dural space.


Exuberant blood flow in enlarged lymph nodes: findings on color flow Doppler. Ten cases of adenopathy, 7 inflammatory and 3 lymphomatous in origin, with visible increased blood flow on color flow Doppler examination are presented. Although the ultrasonic demonstration of blood vessels in enlarged lymph nodes, both inflammatory and tumoral, is not new [1-5], we believe that this is the 1st definitive documentation with color flow Doppler. In some cases the degree of flow was striking, reflecting high velocity flow. This occurred both with inflammatory and lymphomatous nodes and we present our findings 1st to bring attention to them and 2nd to stimulate further investigation of the phenomenon.


Sonographically demonstrated thickening of the renal pelvis in children. Thickening of the wall of the renal pelvis has been attributed to infection, to rejection in allografts and to non-specific causes by different authors. We reviewed the clinical data, imaging studies and pathology of 35 patients with sonographically demonstrable thickening in 41 renal pelves of native kidneys. Our findings are that less than 50% of the patients had infection. The others had a wide variety of apparent causes for the thickening which include obstruction, surgery, edema induced by chemicals and other processes. Vesicoureteral reflux was demonstrated in 50% of the patients studied by cystography. We concluded that renal pelvic thickening is a non-specific finding.


Ultrasound in the early diagnosis of congenital dislocation of the hip: the significance of hip stability versus acetabular morphology. Recent studies have suggested that ultrasound examinations may improve diagnostic accuracy in congenital dislocation of the hip, but there is differing opinion whether ultrasound diagnosis should be based on morphology or stability. Ultrasound was added to the routine clinical screening in 1503 newborns (1291 girls and 212 boys). Hip morphology was classified according to Graf (type 1-4), while sonographic stability was based on a modified Barlow maneuver, and classified as stable, elastic deflection (normal finding), unstable (provocating a gap between the femoral head and the acetabulum) and dislocated. Among 80 morphologically dysplastic hips, 73 (91%) were sonographically unstable or dislocated, while seven dysplastic hips were stable. On the other hand, in 49% of the sonographic unstable hips (69 out of 142) the acetabulum was either normal or just physiologically immature. 38 of these hips were left untreated and normalized spontaneously. There was a close correlation between sonographically and clinically determined hip stability (gamma = 0.95). Our study shows that the majority of morphologically dysplastic hips is sonographically unstable or dislocated, but also that morphologically dysplastic hips may be stable. Morphologically normal hips showing minor sonographic instability do probably not require treatment, and thus morphology seems to be an important diagnostic criterion.


Skeletal growth in cartilage-hair hypoplasia. A radiological study of 82 patients. Cartilage-hair hypoplasia is a metaphyseal chondrodysplasia with short-limbed short stature. In childhood radiographs the metaphyseal regions of the tubular bones are widened, scalloped and irregularly sclerotic. We have analyzed radiological characteristics and skeletal growth in 149 radiographic surveys of 82 Finnish patients. All extremity long bones were affected and short for age. The growth failure was progressive. In the adults the median relative lengths were for the humerus -6.3 SD, radius -8.6 SD, ulna -6.7 SD, femur -9.7 SD, tibia -8.7 SD, and fibula -6.8 SD. the severity of the metaphyseal changes correlated with the degree of the growth failure. The skeletal age was markedly retarded in 14% of the patients. Caudal widening of the interpediculate distance in the lumbar spine was observed in 90% of the patients, but it tended to be less than normal. The sagittal diameter of the spinal canal was normal in the cervical region but decreased in the lumbar region. Mild scoliosis was observed in one-fourth of the patients, and its incidence increased with age. Lumbar lordosis was moderately increased. Thoracic deformity was observed in 82% of the patients. The relative interorbital distance was increased with the median of +2.2 SD in the adults.


Value of MRI and MIBG-I123 scintigraphy in the diagnosis of spinal bone marrow involvement in neuroblastoma in children. The results of MRI and MIBG scintigraphy performed on the spine of 14 children with neuroblastoma are reported. In 6 cases of diffuse spinal bone marrow tumor infiltration, diagnosis is easier with MIBG scintigraphy than with MRI. In 5 cases, MRI detected hyposignal of the vertebral body without any spinal abnormality on MIBG scintigraphy. A discussion of the reasons for negative MIBG scintigraphy is presented and in these 5 cases, it is suggested that a lateral view of MIBG scintigraphy and HMDP-Tc99m scintigraphy may be performed, even vertebral body biopsy in order to assess bone marrow tumoral infiltration.


Eosinophilic granuloma simulating an aggressive rib neoplasm: CT evaluation. Eosinophilic granuloma of bone can pose difficulties in diagnosis. We report a case of eosinophilic granuloma of rib origin in a child presenting with an enlarging chest mass whose appearance on computed tomography suggested Ewing sarcoma. Eosinophilic granuloma should be included in the differential diagnosis of an aggressive rib mass on CT in the pediatric patient.


Primary endodermal sinus tumor of the liver detected by CT. We report a case of primary endodermal sinus tumor of the liver. Endodermal sinus tumors are rare neoplasms which usually arise in the testis or ovary. Extragonadal endodermal sinus tumors are uncommon and primary tumors of the liver are very rare. The tumor was detected using CT and the diagnosis was made by percutaneous biopsy.


Radiological assessment of duodenal calibre in congenital duodenal obstruction. A review of barium meal studies in 32 cases of congenital intrinsic duodenal obstruction (CDO) from the Adelaide Children's Hospital was performed to assess and measure pre and post operative duodenal dilatation. Comparisons were made with a group of 153 normal barium studies from the same Hospital with a view to quantifying normal and abnormal proximal duodenal calibre. Duodenal size was expressed as a ratio D1/L1, (diameter of 1st part of duodenum/height of first lumbar vertebra). In this study a normal range of duodenal diameter was found to be 0.90 to 1.62 (+/- 2 SD from mean), with a mean of 1.26. The CDO patients recorded a range of postoperative ratios on first follow-up barium studies of between 1.2 and 4.5 with a mean of 2.28. Where serial studies had been performed, duodenal diameter was found to show some decrease in size postoperatively. In patients who underwent surgery for membrane obstruction there was a trend towards normalisation of duodenal diameter over time, compared with the atresia group. However, this difference did not reach statistical significance.


Pelvic injuries in child abuse.

Pelvic injuries in child abuse. Three cases of child abuse are described in which pelvic injuries were prominent findings on radiologic examination: Two patients had pelvic fractures, and one was found to have heterotopic ossification of the soft tissues of the pelvis and thighs corresponding to extensive bruising in the pubic, genital, buttock, and thigh areas, resulting from physical and sexual abuse. These represent uncommon radiographic findings. Skeletal survey in cases of suspected child abuse should include the entire pelvis, and special attention should be paid to the ischiopubic rami the most common site of these rare pelvic injuries.


Pediatric craniofacial surgery: comparison of milling and stereolithography for 3D model manufacturing. To improve the planning phase for pediatric craniofacial surgery, 3D reconstructions of CT image series were performed on a personal computer. For construction of true models of the surgical site, two concepts were pursued. CT image data of six patients were used for model manufacturing by a conventional 2 1/2 axis milling system. The material used was polyurethane foam. Alternatively, in one patient a stereolithography was produced on the basis of the 3D reconstructed CT data. This new manufacturing device uses a photocurable monomer, hardened by a UV-laser. The spatial resolution of the system is about 0.1 mm. 3D-reconstructions were performed on a personal computer. Data were then transferred into a surface oriented structure to control a stereolithographic modeling device. Time for transfer was 70 min. The production of the modelled cranium took a total time of 59 h. Accuracy was found to be much higher in stereolithography than in milled models. The model served for surgical planning. The long time for production was caused by inadequate computer capacities, which are configured for much less complex objects in computer aided design. Furthermore the programs for the machine control are optimized for technical purposes. If these conditions are improved, stereolithography could be an attractive alternative to milling of medical models.


The fibrous metaphyseal defect in early stage. Differential diagnosis to metaphysitis. In a 22-month-old boy a fibrous metaphyseal defect (FMD) was diagnosed by radiological follow-up examinations. The initial radiological finding could not be differentiated from metaphysitis because of its early manifestation and stage. Eleven months later, magnetic resonance imaging (MRI) with Gadolinium (Gd)-DTPA demonstrated a small central area of increased signal intensity. Based on known angiographic findings with fibrous metaphyseal defects, one may hypothesize that this is best explained by a hypervascularized area.


MR imaging of breast hemangioma in female infants. Breast hemangioma in female infants is a rare benign lesion, prone to spontaneous regression. But when the lesion regresses there is a risk of breast atrophy if the breast bud is included in or very close to the hemangioma. A trial of corticosteroid therapy could be proposed to prevent this risk, but one must be sure that the breast bud is included in or very close to the hemangioma before treatment. We studied 4 children with breast hemangioma to evaluate the ability of MR Imaging in the diagnosis of breast bud inclusion. 0.5 Tesla axial Spin Echo T2-weighted images (TR = 2000 ms; TE = 120 ms) clearly depicted interface between high signal appearance of hemangioma and hypo-intensity of the breast bud: in our four patients we were able to determine whether or not the hemangioma involved the breast bud. Our preliminary study seems to demonstrate that MR imaging is a valuable imaging technique to determine which patients could be eligible for a trial of corticosteroid therapy.


Asymptomatic myelolipoma of the adrenal. Myelolipoma of the adrenal gland is a rare benign tumour which seldom produces symptoms unless it attains considerable size or hemorrhages into itself. Histologically the tumor is composed of varying proportions of fat and bone marrow elements. We present a case of a male child, with homozygous beta thalassemia and asymptomatic myelolipoma.


Inflammatory pseudotumor of the lung manifesting as a posterior mediastinal mass. A case of inflammatory pseudotumor of the lung in a 6-year-old boy is presented. The respiratory illness presented as a mycoplasma pneumonia and there had been a similar episode of mycoplasma pneumonia one and a half years previously. Computed tomography revealed a large, calcified right posterior mediastinal mass and exploratory thoracotomy revealed a large posterior mediastinal mass that had an endobronchial component and grew exophytically from the lung. The present case suggests that inflammatory pseudotumor of the lung can manifest as a mediastinal mass and could be associated with mycoplasma pneumonia infection.


Ultrasound diagnosis of an atypical pneumomediastinum. The diagnosis of an atypical pneumomediastinum in a newborn was confirmed by ultrasound where an echogenic rim of air was noted around the heart. Ultrasound is suggested as an alternative to a decubitus film in differentiating between a pneumomediastinum (which usually resolves spontaneously) and a medial pneumothorax (which requires drainage).


Two unusual cases of nephrocalcinosis in infancy. Nephrocalcinosis is uncommon in childhood, the main causes are renal tubular acidosis, hyperparathyroidism and medullary sponge kidney. It is also seen where there is hypercalcaemia or hypercalciuria of any aetiology; We report nephrocalcinosis in an 18-month-old infant with metaphyseal chondrodysplasia type Jansen and also in a neonate with McCune Albright syndrome who displayed atypical skeletal appearances and had multiple ovarian cysts.


MR imaging and sonography of Gartner's duct cyst and single ectopic ureter with ipsilateral renal dysplasia. An 8-year-old girl with a rare anomaly of a single ectopic ureter to the Gartner's duct cyst and ipsilateral renal dysplasia is presented. MR imaging and ultrasound were utilized to make the diagnosis.


Radiographic findings in Wiedemann-Rautenstrauch syndrome. We describe a girl who presents the features of Wiedemann-Rautenstrauch syndrome. This autosomal recessive condition has characteristic radiographic findings which can be considered manifestations of the syndrome.


Rational design of conjugate vaccines.

Rational design of conjugate vaccines. Whereas bacterial polysaccharides, classified as T-cell-independent antigens, elicit protective antibodies in adults, booster injections fail to produce an augmented response or promote antibody class switching. Because T-cell-dependent antigens, typically proteins, both produce boosted antibody levels and promote antibody class switching, it has been considered highly desirable to attempt to convert the T-cell-independent polysaccharide antigens into T-cell-dependent antigens, particularly for use in high-risk groups. A number of clinical trials now report the efficacy of conjugate vaccines in inducing the production of antibody in response to a number of previously poorly immunogenic--mainly T-cell-independent--antigens. In addition to conjugate vaccines containing bacterial polysaccharides, vaccines containing relevant peptides from a variety of pathogens are also being formulated and investigated. Questions remain, however, regarding their synthesis, use, and efficacy. The best ages for vaccine administration and selection of the optimal protein carrier are still under investigation, as are questions regarding the use of adjuvants, which can greatly affect the vaccine's potency. Spacing and size of epitope and size and composition of the final structure also must be considered; the importance of molecular size and aggregation of antigen in increasing immunogenicity have been well documented. These questions must be addressed for the much-needed development of conjugate vaccines against some common infections worldwide, including malaria, bacterial meningitis, and infections from Pseudomonas aeruginosa and Neisseria gonorrhoeae because of increasing susceptibility to these infections and resistance of the pathogens to chemotherapeutic agents and/or antibiotics.


In situ morphology of the ductus venosus and related vessels in the fetal and neonatal rat. In situ cross-sectional morphology of the ductus venosus and related vessels was studied after rapid whole-body freezing of the fetal and neonatal rat. In the fetus, the ductus venosus was open widely, connecting the umbilical sinus and the inferior vena cava. The diameter of the ductus venosus was 50% of the diameter of the umbilical sinus. The ductus venous joined the left dorsal side of the inferior vena cava. A thin, short, membrane-like edge was present at the inner junction of the ductus venosus and the inferior vena cava, presumably effecting laminar flow of the ductus venosus blood to the left side of the thoracic inferior vena cava. A very prominent eustachian valve was present at the junction of the inferior vena cava and the right atrium, presumably directing its flow to the opening of the foramen ovale. After birth, the ductus venosus narrowed rapidly and closed completely in 2 d. The closing ductus venosus was tubular, with the cranial end slightly wider than the caudal portion. Localized constriction was not present. These observations showed the structural substrate for preferential flow from the ductus venosus to the foramen ovale and left atrium in the fetus and did not support localized sphincter mechanism in postnatal closure of the ductus venosus.


Fate of the atrioventricular endocardial cushions in the developing chick heart. To determine the fate of the atrioventricular endocardial cushions in cardiac development, we used staining methods for extracellular fibronectin, which is abundant in the endocardial cushions, and actin, which is abundant in the myocytes. White Leghorn chick embryo hearts were harvested at Hamburger and Hamilton stages 26 to 36, and serial sections of the atrioventricular valve region were stained. Before atrioventricular valve formation, fibronectin and actin staining reveal separation between the fibronectin-rich endocardial cushions and the actin-rich myocardial layer. The developing mitral valve leaflets at all of the observed stages contain a fibronectin-rich matrix but no actin-rich myocytes. In contrast, the tricuspid band includes both fibronectin matrix and actin-rich cells. We conclude that the mitral valve leaflets in the chick form predominantly from the endocardial cushion tissue, and the tricuspid band receives contributions from both the endocardial cushions and surrounding myocardium.


Nitrofen-induced diaphragmatic hernias in rats: pulmonary antioxidant enzyme activities. We developed an experimental rat model of congenital diaphragmatic hernia (CDH) to elucidate the etiology and pathogenesis of this serious congenital anomaly in humans and in particular to study the effects of a short period of artificial ventilation on the CDH lung in relation to antioxidant defense mechanisms. CDH was induced in about 60% of the offspring by maternal exposure to 2,4-dichlorophenyl-p-nitrophenylether (Nitrofen) during pregnancy. This herbicide resembles thyroid hormone in chemical structure. The lungs of fetal rats (d 19, 20, 21, and 22) were examined for protein and DNA content and activity of superoxide dismutase, catalase, and glutathione peroxidase (GPX). The same parameters were assessed in tracheotomized newborn rats after pressure-controlled artificial ventilation with either room air or pure oxygen during a short period of 5 h. In both CDH rats and controls, wet lung weight increased during gestation. At term, CDH rats had significantly lower mean lung weights than controls. Neither group differed in protein and DNA content per mg lung or superoxide dismutase, catalase, and GPX activity before and at birth. After artificial ventilation of neonates with air and pure oxygen, superoxide dismutase activity tended to decrease, whereas catalase activity remained virtually unchanged in the CDH lung. However, GPX activity in the CDH lung was reduced to 80% of initial activity at term after ventilation with air and to 70% with pure oxygen. The present finding of a decline in GPX activity in this animal model after a short period of artificial ventilation may indicate that the CDH rat neonate is at risk to develop oxygen-related lung damage.


Recycling of glutathione during oxidative stress in erythrocytes of the newborn. The ability of erythrocytes from newborn babies and adults to maintain reduced glutathione levels during oxidative stress was studied. In vitro incubation of erythrocytes with H2O2, with or without inactivation of catalase, caused a rapid depletion of reduced glutathione (GSH) and concomitant accumulation of oxidized glutathione followed by recovery of GSH and fall of oxidized glutathione to initial values in all subjects. Inactivation of catalase resulted in a 50% loss of intracellular glutathione (p less than 0.005), a larger maximum GSH depletion (p less than 0.05), and a longer GSH recovery time (p less than 0.005). Erythrocytes from newborn babies showed a smaller maximum GSH depletion (p less than 0.05) and a shorter GSH recovery time (p less than 0.005) compared with those from adults. These differences between the newborn and adult groups persisted after inactivation of catalase. An increase in maximum GSH depletion and GSH recovery time (p less than 0.005) was observed when a lower hematocrit was used for these GSH recovery studies. Effective glutathione recycling in erythrocytes may protect immature tissues of the newborn baby from peroxidative damage.


Small preterm infants (less than or equal to 1500 g) have only a sustained decrease in ventilation in response to hypoxia. The classic "biphasic" ventilatory response to 15% O2 was previously observed in preterm infants who were large compared with those in the intensive care nursery today. We hypothesized that in the smaller infant (less than or equal to 1500 g) the response might be closer to that of the fetus, with no initial increase in ventilation. Thus, we studied 14 healthy preterm infants less than or equal to 1500 g [birth weight 1200 +/- 63 g (mean +/- SEM); gestational age 29 +/- 0.4 wk; postnatal age 17 +/- 3 d] during rapid eye movement and quiet sleep. Ventilation was measured using a nosepiece and a flow-through system. Sleep states were defined using EEG, electro-oculogram, and body movements. After a control period in 21% O2 (3 min), infants breathed 15% O2 for 5 min. In rapid eye movement sleep, minute ventilation decreased from 0.186 +/- 0.020 (control) to 0.178 +/- 0.021 (30 s), to 0.171 +/- 0.017 (1 min; p = 0.03), to 0.145 +/- 0.016 (3 min; p = 0.002), and to 0.129 +/- 0.011 l.min-1.kg-1 (5 min; p = 0.004). In quiet sleep, it decreased from 0.173 +/- 0.019 (control) to 0.164 +/- 0.019 (30 s), to 0.166 +/- 0.019 (1 min), to 0.148 +/- 0.013 (3 min; p = 0.03), and to 0.146 +/- 0.012 l.min-1.kg-1 (5 min; p = 0.04).(ABSTRACT TRUNCATED AT 250 WORDS)


Prenatal thyroid releasing hormone and thyroid releasing hormone plus dexamethasone lessen the survival of newborn rats during prolonged high O2 exposure. Newborn rats prenatally treated with TRH or the combination of TRH + DEX have lower lung antioxidant enzyme activities at birth than control newborns but are able to induce an adaptive antioxidant enzyme response to hyperoxic exposure of similar or even greater magnitude compared to O2 control offspring. Because of this greater antioxidant enzyme response, we hypothesized that the hormonally pretreated newborns might demonstrate superior tolerance to prolonged high O2 exposure. However, when placed in greater than 95% O2 at birth, the survival rates were consistently lower in the TRH- and TRH + DEX-treated pups at all time periods in hyperoxia from 9 d [control = 74 of 92 (80%); TRH + DEX = 32 of 47 (68%); TRH = 29 of 48 (60%); p less than 0.05] to 14 d [control = 43 of 92 (47%); TRH + DEX = 11 of 47 (23%); TRH = nine of 48 (19%); (p less than 0.05)]. Other evidence of poorer O2 tolerance in the prenatal hormone-treated pups included a greater incidence of intraalveolar edema and elevated lung conjugated dienes, an index of lipid peroxidation, at 3, 5, and 7 d of O2 exposure. There was also a persistent elevation in 3,5,3'-triiodo-L-thyronine and thyroxine serum levels in the 10-d-old TRH-treated offspring. We conclude that prenatal TRH treatment, possibly working through the secretion of 3,5,3'-triiodo-L-thyronine and thyroxine, has some important lasting postnatal effect (not completely reversed by dexamethasone) that predisposes newborn rats to greater O2 radical-induced lung sequelae of prolonged hyperoxic exposure.


Neonatal pattern of breathing during active and quiet sleep after maternal administration of meperidine. The aim of this study was to reappraise the effects of maternal meperidine administration on breathing pattern during the first hours of life taking into account the state of alertness. Because breathing instability is more pronounced during active sleep, we hypothesized that meperidine administration might create a greater risk for respiratory instability during active sleep, the prominent sleep state in newborns. We studied eight full-term, healthy newborns whose mothers had received a continuous i.v. infusion of meperidine (81 +/- 9 mg) that was terminated 5.5 +/- 2.1 h before delivery. These infants were compared with a control group of eight full-term newborns whose mothers did not receive any opioids. In both groups, all babies were delivered vaginally after a normal labor and had Apgar scores of 9 or 10 at 1 and 5 min. Neonatal gastric secretion and maternal venous and umbilical venous blood were sampled at delivery for determination of meperidine concentration. From 60 to 300 min after delivery, behavioral sleep states and thoracic and abdominal movement as well as transcutaneous arterial oxygen saturation (SaO2) were monitored continuously. The number of apneic spells lasting more than 3 s during 100 min of recording and the percentage of time with SaO2 below 90% in each sleep state were recorded. During quiet sleep, all respiratory variables were similar in both groups. During active sleep, there were significantly more apneic episodes (37.1 +/- 25.1 versus 11.2 +/- 13.9) and a higher percentage of time with SaO2 less than 90% (14.3 +/- 16.7% versus 1.3 +/- 1.5%) in the meperidine group than in the control group (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)


The relationship between environmental temperature, metabolic rate, sleep state, and evaporative water loss in infants from birth to three months. We have investigated the effect of changing environmental temperature on metabolic rate, sleep state, and water loss in a longitudinal study of 22 lightly clothed babies from 2 d to 3 mo of age. Studies were performed in a modified barometric plethysmograph while recording sleep state, oxygen consumption, and skin and axillary temperatures. Oxygen consumption was higher in rapid eye movement sleep than in quiet sleep at all ages and varied widely between infants at each temperature. Within the first week, there was a 19% rise in oxygen consumption on cooling to 19-22 degrees C during rapid eye movement sleep and a 6% rise during quiet sleep. The median duration of quiet sleep periods was reduced from 17 to 12 min on cooling within the first week. No such change was seen at 1, 2, and 3 mo. Axillary temperature was reduced at 3 mo during cooling. This may be a part of normal patterns of change in temperature during sleep, unrelated to cooling. At each age, total evaporative water loss fell linearly with falling environmental temperature both within and below the temperature range at which metabolic rate was minimal. The evaporative water losses were greater than expected and suggested that sweating was occurring, both at temperatures at which metabolic rate was minimal and at those at which it was increased. The metabolic response to cooling and the process of sweating appear to be in dynamic equilibrium across this temperature range. Thus, it was not possible to define a temperature range over which both metabolic rate and evaporative water loss were at minimum values.


Expression of pulmonary metallothionein genes in late gestational lambs. Metallothioneins (MT) are low molecular weight proteins that are important in providing protection against heavy metals such as cadmium. Other precise physiologic roles for this family of proteins are less clear, but fetal hepatic cell proliferation and differentiation may be regulated through changes in MT levels and attendant MT-mediated regulation of zinc levels. The role of MT in other developing tissue, most notably lung, is far less clear. Although expression of MT has been reported to be extremely low in early postnatal and mature lung, we hypothesized that MT has a more ubiquitous role in organ development and that pulmonary MT levels may be elevated during periods of rapid lung growth. Thus, we studied expression of MT in late-gestation fetal lambs. Sheep are particularly useful because alveolarization of lung parenchyma occurs before birth (by d 120 of a normal 147-d gestation). Immunoreactive MT was localized to bronchial epithelium of fetal, newborn, and mature sheep. The intensity of staining was greatest in the 130-d gestational age (saccular) lung, where positive reaction product was noted in the cytoplasm and nucleus of alveolar epithelial and interstitial cells. We next evaluated MT expression in developing lung tissue using Northern blot analysis and 32P-cDNA probes against the 3'-untranslated regions of mRNA encoding each of four known functional sheep MT (sMT) isoforms. Expression of sMT-II, sMT-Ia, and sMT-Ib was restricted to the saccular stage (120-132 d gestational age), and sMT-Ic mRNA was not detected in pulmonary samples from any stage of development.(ABSTRACT TRUNCATED AT 250 WORDS)


Activation of the plasma kallikrein-kinin system in respiratory distress syndrome. Components of the plasma kallikrein-kinin and fibrinolytic systems together with antithrombin III were measured the first days postpartum in 13 premature babies with severe respiratory distress syndrome (RDS). Seven of the patients received a single dose of porcine surfactant (Curosurf) as rescue treatment. Nine premature babies without lung disease or any other complicating disease served as controls. There were no differences in prekallikrein values between surfactant treated and non-treated RDS babies during the first 4 d postpartum. The controls had, however, significantly higher prekallikrein values than the RDS babies already at the first day of age (mean +/- SD 32 +/- 8% in controls versus 22 +/- 6 and 21.5 +/- 5% in the treated and nontreated RDS groups, respectively). Plasma kallikrein activities did not differ between RDS and control patients. Plasma kallikrein inhibition values, which increased steadily in all groups, were lower in the RDS babies treated with surfactant than in controls at d 2 and 4. The degree of degradation of plasma high molecular weight kininogen was measured in RDS patients treated with surfactant and was significantly higher when compared with controls at d 1, demonstrating an increased proteolysis of kininogen to kinin early in RDS. There were no differences in plasminogen and plasmin values between RDS and control babies. This study shows that the plasma kallikrein-kinin system is activated in RDS. This system as well as the fibrinolytic system does not seem to be influenced by rescue instillation of a single dose of porcine surfactant into the lungs of premature babies with RDS.


Differential effects of short and long durations of insulin-induced maternal hypoglycemia upon fetal rat tissue growth and glucose utilization. We studied the effects of short and long durations of insulin-induced maternal hypoglycemia upon in vivo glucose utilization of several fetal tissues in the rat. Osmotic minipumps filled with insulin were implanted in pregnant rats on d 15 or 18 of gestation (term 21.5 d), and radiolabeled 2-deoxyglucose was used to measure relative glucose utilization rates (rGU) of fetal liver, lung, muscle, kidney, heart, placenta, and brain on d 20 of gestation after 2 or 5 d of hypoglycemia. Maternal plasma glucose concentrations decreased within 24 h of pump placement and remained less than controls throughout gestation. Fetal plasma glucose and insulin concentrations on d 20 were equally reduced after 2 and 5 d of hypoglycemia. Both 2 and 5 d of hypoglycemia were associated with significant reductions in the rGU of fetal liver, lung, and muscle. Reductions in fetal kidney rGU also occurred after 2 and 5 d of hypoglycemia but to a smaller degree. rGU of fetal heart was reduced after 2 d of hypoglycemia, but was normal after 5 d of hypoglycemia. Both 2 and 5 d of hypoglycemia were associated with increased rGU of fetal brain. Five d, but not 2 d of hypoglycemia resulted in decreased fetal weight on d 20 of gestation. However, at term, newborn pups delivered of hypoglycemic mothers weighed significantly less than controls regardless of the timing of minipump placement. Liver, lung, and carcass of these growth-retarded pups weighed less than control tissues, whereas kidney, heart, and brain weights were not affected.(ABSTRACT TRUNCATED AT 250 WORDS)


The metabolism of free fatty acids and triacylglycerols by the fetal liver in a guinea pig model of intrauterine growth retardation. The aim of this study was to determine whether intrauterine growth retardation (IUGR) is associated with an alteration in hepatic lipid metabolism. IUGR was induced in 25 guinea pigs by uterine artery ligation on gestational d 30. On d 62, after anesthesia, an infusion of [1-14C]-palmitic acid was given. Fetuses were exposed at 15, 30, and 45 min, and simultaneous maternal and umbilical venous blood samples were taken. Livers were divided into right lobe, right and left sublobes of the quadrate lobe, and left lobe. In control fetuses, plasma radiolipids rose in parallel with, but were about half the value of, maternal levels. In IUGR fetuses, plasma radiolipids were lower than in controls at 15 and 30 min but were comparable at 45 min. Most of the radiolipid in the maternal plasma was FFA, with only 6% incorporated into triglycerides at 45 min. In control and IUGR fetal plasmas, 36-37% of the radiolipid was triglycerides by 45 min. Radiolabel incorporation into the right lobe was less than into the left lobe and left half of the quadrate lobe in control and IUGR fetuses. Compared with controls, radiolabel incorporation in IUGR fetuses was less in some or all liver lobes at each time point. The proportion of label associated with FFA and triglycerides did not vary with time, between lobes, or between control and IUGR fetuses. The difference in uptake between lobes reflects their blood supply, implying that most FFA is extracted during the first passage of the umbilical venous blood. Growth retardation was not associated with compromised hepatic FFA metabolism.


Changes in protein turnover after the introduction of parenteral nutrition in premature infants: comparison of breast milk and egg protein-based amino acid solutions. Rates of protein turnover were measured in 20 infants receiving either Vamin Infant (group A) or Vamin 9 glucose (group B) as the amino acid source in total parenteral nutrition. A constant infusion of L-[1-13C]leucine was used to measure whole body leucine flux, and leucine oxidation rates were derived from measurements of total urinary nitrogen excretion. Infants were first studied when receiving only i.v. glucose and again on each of the next 4 d as total parenteral nutrition was gradually increased to a maximum of 430 mg nitrogen/kg/d and 90 nonprotein kcal/kg/d. Net protein gain and protein synthesis and breakdown rates increased progressively for all infants taken together over the study period as i.v. nutrition was increasing (p less than 0.001). There were no differences between groups in the changes in net protein gain and rates of protein synthesis and breakdown throughout the study period. Nitrogen retention on d 5 for the two groups was similar (60 +/- 16% and 67 +/- 11% in groups A and B, respectively). In a subgroup of infants, measurements were repeated on d 8, when the intake had been constant for 3 d. Protein retention was the same as on d 5, but both synthesis and breakdown were increased. It is concluded that rates of protein turnover increase significantly in response to increasing i.v. nutrition and that this elevation was not influenced by the composition of the amino acid mixture given.


Low prevalence of autoantibodies to the insulin-like growth factor I receptor in children with short stature. Inhibition of IGF-I action by circulating IGF-I receptor autoantibodies is a potential mechanism of IGF-I resistance in growing children. To define the prevalence of IGF-I receptor antibodies in short-statured children, we have examined serum and plasma samples from a well-characterized group of 34 short, prepubertal, growth hormone-sufficient children and three growth hormone-deficient children. IGF-I receptor purified from human placental membranes was radioiodinated by the solid phase radioiodination method. Serum from a patient with severe insulin resistance immunoprecipitated 28.9-44.7% of the 125I-labeled IGF-I receptor. The ranges (mean +/- 3 SD) of 125I-labeled IGF-I receptor immunoprecipitated by 1:10 diluted and by undiluted nonimmune human serum were 1.99 +/- 0.63% and 4.42 +/- 1.32%, respectively. Immunoprecipitation of the 125I-labeled IGF-I receptor by eight samples from six children was greater than 3 SD above the mean when assayed at a 1:10 dilution. Nevertheless, when assayed undiluted, only one of these samples immunoprecipitated slightly more 125I-labeled IGF-I receptor than nonimmune serum. We conclude from these data that immunoprecipitating autoantibodies to the IGF-I receptor are not commonly present in short-statured children.


Role of tumor necrosis factor-alpha and interferon-gamma in newborn host defense against Listeria monocytogenes infection. The fetus and newborn are particularly susceptible to Listeria monocytogenes infection. We used a newborn rat animal model to investigate neonatal host defense against Listeria. In this animal model, newborn (3-d-old) rats are more susceptible to L. monocytogenes than older animals. Juvenile (23-d-old) L. monocytogenes-infected rats pretreated with lipopolysaccharide (LPS) had a lower bacterial load in blood than control animals, whereas LPS pretreated newborn rats had a higher bacterial load. Because LPS is a potent inducer of tumor necrosis factor (TNF) and TNF enhances host defense against this organism in adult animals, we assessed TNF content in splenic homogenates for animals of different ages. The age at which TNF was detectable in L. monocytogenes-Infected rats corresponded to the age at which LPS became active in preventing severe bacteremia. TNF was less than 1 unit/mL in splenic homogenates taken from rats less than 8 d of age, whereas 16-d-old rats infected with L. monocytogenes 1 d earlier had greater than 80 units/mL (p less than 0.0001 for 3-d-old versus 16-d-old rats). We also assessed the responsiveness of rats to exogenous TNF-alpha. Juvenile rats pretreated with TNF-alpha before L. monocytogenes infection had decreased bacterial load in spleen (p less than 0.02 versus controls) and better survival at 7 d (p less than 0.05 versus controls), whereas newborn rats did not improve with TNF-alpha pretreatment (p greater than 0.05 treated versus controls for splenic bacterial load and 7-d survival).(ABSTRACT TRUNCATED AT 250 WORDS)


Characteristics of L-citrulline transport across rat small intestine in vitro. The amino acid L-citrulline is an important intermediate of urea cycle and a key precursor for arginine biosynthesis. We have examined the characteristics of citrulline transport across the everted sacs of the rat small intestine. Our studies suggest that the optimal site of citrulline absorption is middle to lower ileum. It shows active transport, and this transport is predominantly Na+ dependent. Its uptake is significantly inhibited by ouabain, dinitrophenol, sodium azide, and sodium cyanide. Kinetic estimation reveal an apparent substrate concentration at 1/2 maximum velocity of 4.10 +/- 0.86 mM and a Vmax of 18.7 +/- 1.66 mumol/g wet weight tissue/30 min. Analog inhibition studies suggest that citrulline may share the neutral brush border system described for the mucosal brush border membranes of the rabbit jejunum or a system analogous to system ASC described for nonepithelial cells and for basolateral membranes of certain epithelia. In conclusion, the rat small intestine has developed a specific carrier-mediated, Na(+)-dependent pathway for citrulline absorption.


Prolidase deficiency in cultured human fibroblasts: biochemical pathology and iminodipeptide-enhanced growth. Prolidase deficiency is a rare autosomal recessive disorder characterized by iminodipeptiduria, severe skin ulcers, recurrent infections, and mental retardation. The enzyme prolidase hydrolyzes dipeptides containing C-terminal proline or hydroxyproline. We investigated the metabolic abnormality caused by prolidase deficiency in human cultured skin fibroblasts. These studies were undertaken to test biochemical hypotheses regarding the metabolic origins of the skin lesion occurring in this disease. Our results indicate that prolidase plays a major role in the recycling of dipeptide-bound proline. Control fibroblasts were able to use iminodipeptides in lieu of proline to sustain normal growth, whereas cells homozygous for the prolidase deficiency mutation were not. Proline derived from iminodipeptides diluted incorporation of radiolabeled extracellular proline into cellular protein in normal cells but not in mutant cells. Substitution of a prolidase-free medium for FCS did not affect the growth rate of control cell lines but increased the doubling time of prolidase-deficient cells by 19% (28% in the presence of iminodipeptides). Iminodipeptides added to control and mutant cells maintained in serum-free medium showed no adverse effects on protein synthesis. These results are consistent with a mechanism of biochemical pathology in which proline deprivation caused by the enzyme deficit is a primary cause of damage to skin cells. Prolidase regulation by product and substrate was studied. A 44% decrease in activity was observed in fibroblasts grown for 3 wk in proline-containing medium relative to proline-free medium. However, cells grown in medium in which iminodipeptides replaced proline showed no significant difference in prolidase activity.