[Juvenile hyaline fibromatosis]. / Juvenile hyaline Fibromatose.

Juvenile hyaline fibromatosis is a rare autosomal recessive disease of the connective tissue. We present the case of a 6-year-old normal mental developed boy with confluent pearly papules behind the ears and in the paranasal folds, firm nodules of the scalp, the back and metaphalangs, and severe gingival hypertrophy.

Surfactant Metabolism Dysfunction and Childhood Interstitial Lung Disease (chILD).

Surfactant deficiency and the resultant respiratory distress syndrome (RDS) seen in preterm infants is a major cause of respiratory morbidity in this population. Until recently, the contribution of surfactant to respiratory morbidity in infancy was limited to the neonatal period. It is now recognised that inborn errors of surfactant metabolism leading to surfactant dysfunction account for around 10% of childhood interstitial lung disease (chILD). These abnormalities can be detected by blood sampling for mutation analysis, thereby avoiding the need for lung biopsy in some children with chILD.

ABCA3 Deficiency: an unusual cause of respiratory distress in the newborn.

Respiratory Distress Syndrome (RDS) is due to deficiency of surfactant and commonly occurs in preterm babies. We report the first confirmed case in Northern Ireland of ABCA3 transporter deficiency which is a rare but important cause of RDS in term babies.A 38 week gestation female infant developed respiratory distress at four hours of age. Chest radiography was consistent with RDS. The baby required repeated doses of surfactant, each resulting in transient periods of decreased ventilatory requirement and improvement in blood gases, but unfortunately she did not survive.DNA sequencing demonstrated two different mutations in the ABCA3 gene, one inherited from each parent. The baby was therefore a compound heterozygote, and both mutations were thought to be functionally significant.ABCA3 transporter deficiency is a genetic disorder that is increasingly recognized as a cause of RDS in term babies in whom congenital deficiency of surfactant B and abnormalities of surfactant protein C have been excluded. It should be considered in mature babies who develop severe RDS.

Pulmonary Hyalinising Granuloma: A report of two cases.

Pulmonary hyalinising granuloma (PHG) is a rare fibrosclerosing inflammatory lung condition of unknown aetiology. It is characterised by solitary or multiple pulmonary nodules that are usually found incidentally while imaging the chest for other reasons. We report two cases of histologically proven PHG diagnosed at the Royal Hospital, Muscat, Oman. The first case was a 71-year-old male patient who presented in 2010 with a dry cough, weight loss and bilateral pulmonary nodules. The second case was a 58-year-old male patient who presented in 2012 and was found to have incidental bilateral pulmonary nodules on chest X-ray. Both patients were started on prednisolone and on follow-up the PHG nodules remained stable. Although there is no definitive treatment, PHG generally has an excellent prognosis.

A study of spectrum of pulmonary pathology and expression of thyroid transcription factor-1 during neonatal period.

CONTEXT: Neonatal period is the single most hazardous period of life. The major causes of neonatal death are prematurity and respiratory distress syndrome. We report a series of neonatal autopsies in our Neonatal Intensive Care Unit with special emphasis on pulmonary pathology. The spectrum of pathological changes in the lungs and thyroid transcription factor-1 (TTF-1) expression was studied in detail with reference to its spatial distribution. AIMS: This study aims to analyze the causes of neonatal death with special attention to pulmonary pathology along with associated histopathological changes in lungs. We also evaluated the expression of TTF-1 at different levels of the airway. MATERIALS AND METHODS: After taking consent and anthropometric measurements, autopsy was performed. Weights of all organs were taken, and histological sections were examined under hematoxylin and eosin stain. TTF-1 immunostaining was done on lung sections. Localization of TTF-1 was evaluated at the intrapulmonary level of terminal bronchioles (TBs), distal bronchioles, and alveoli. RESULTS: We performed a series of 25 autopsies in neonates. In our series, most of the neonates were preterm (64%), had low birth weight (44%), and died within the first 7 days of life (80%). Majority (60%) of the neonates died due to pulmonary causes, followed by septicemia (24%), congenital anomalies (12%), and birth injury (4%). Among the respiratory causes, hyaline membrane disease (HMD) was diagnosed in maximum number of cases (32%), followed by pneumonia (12%) and pulmonary hemorrhage (12%). The TTF-1 expression in TBs, distal airways, and alveoli was significantly reduced or absent in cases of HMD compared to the control group. CONCLUSIONS: In this study, we observed that HMD is the most common cause of perinatal death among respiratory disorders, and in this disease, the expression of TTF-1 is significantly reduced in TBs, distal airways, and alveoli compared to the control group.

[Dynamic change in respiratory mechanic dynamics and its clinical significance during mechanical ventilation in hyaline membrane disease of children].

OBJECTIVE: To explore the characteristics of changes in respiratory mechanic dynamics and clinical significance in hyaline membrane disease (HMD) under mechanical ventilation. METHODS: One hundred and twenty-six newborns with HMD undergoing mechanical ventilation were divided into two groups: complication group with 43 cases and no-complication group with 83 cases. The blood gases and indices of respiratory mechanic dynamics were monitored 2, 24, 48 and 72 hours after the first ventilation and before the first weaning from ventilation. RESULTS: Pulmonary compliance [(0.55+/-0.10) ml.cm H(2)O(-1).kg(-1), (0.43+/-0.10) ml.cm H(2)O(-1).kg(-1)] and minute volume [MV, (0.65+/-0.10) L/min, (0.62+/-0.30) L/min] were elevated compared with that after ventilation for 2-72 hours, however the oxygenation index [OI, (10.2+/-1.9)mm Hg vs. (13.6+/-4.3) mm Hg] significantly lower. The compliance and MV in no-complication group were higher than that in complication group 24 and 48 hours after ventilation. There were no differences in the airway resistance and lung inflation index between two groups. The pulmonary compliance was negatively correlated with OI (r=-0.208, P<0.01) and corrected with MV (r=0.218, P<0.01). In no-complication group, all cases ventilation was weaned successfully at once in all the patients,and their mean compliance and MV were (0.55+/-0.10) ml.cm H(2)O(-1).kg(-1) and (0.65+/-0.20) L/min respectively. However, in complication group, weaning failed 38 patients, their mean compliance and MV were (1.03+/-0.30) ml.cm H(2)O(-1).kg(-1) and (0. 33+/-0.30) L/min respectively. CONCLUSION: Respiratory mechanic dynamics monitoring is beneficial in evaluating the severity of hyaline membrane disease and complications, guiding mechanical ventilation management and weaning.

Clinical diagnosis and management of respiratory distress in preterm neonates: effect of participation in a controlled trial.

The ability to generalize the results of a clinical trial depends on the ability to compare a population of patients with the population described in the trial, emphasizing the importance of objective diagnostic criteria in study design and clinical medicine. However, clinical decisions are often based on subjective interpretations of data. There is concern that bias that an experimental therapy is beneficial might lead to alterations in clinical diagnosis and management. To evaluate this concern, the authors reviewed a preexisting database comprising information obtained by trained personnel by chart review to investigate prospectively the frequency of the diagnosis of hyaline membrane disease and the use of mechanical ventilation before and during participation in a clinical trial of surfactant therapy during which such therapy was available exclusively through clinical trials. Major eligibility criteria for a randomized trial at the Medical University of South Carolina included mechanical ventilation and the diagnosis of hyaline membrane disease. Both the diagnosis of hyaline membrane disease and the use of mechanical ventilation increased between pre-surfactant and randomized trial periods (hyaline: 47.2% to 55.9%, P less than .05; ventilation: 55.6% to 66.3%, P less than .01). The possibility that enthusiasm for surfactant influenced clinical diagnosis and management of respiratory distress during this period cannot be dismissed.

Colloid osmotic pressure in infants with hyaline membrane disease.

Colloid osmotic pressure (COP) was measured serially in 81 critically ill neonates with hyaline membrane disease (HMD) during the first five days of life, and these changes were correlated with the birth weight, gestational age, serum protein level, clinical status, and outcome. Colloid osmotic pressure correlated better with the total protein level (n = 81; r = 0.54) than with birth weight (r = 0.23) and gestational age (r = 0.31; n = 81). Seventy-one of 81 neonates survived. Among the survivors, COP increased significantly by day 5, whereas changes in the total protein level were not significant during the same period. Colloid osmotic pressure decreased significantly in nine of ten nonsurvivors (mean +/- SE, 11 +/- 0.5 to 8 +/- 0.55 mm Hg), whereas the total protein level did not show a similar change. Thus, COP cannot be accurately predicted by measuring serum protein during acute illness. Serial measurement of COP was a better prognostic indicator than the total protein level in infants with HMD.

A safe method of amniocentesis for lecithin/sphingomyelin determination in late pregnancy using ultrasound.

Two hundred consecutive amniocenteses for lecithin/sphingomyelin (L/S) determination in late pregnancy are reviewed. These procedures were performed under ultrasonic control before induction of labor or elective cesarean section in a prospective study to determine a safe method for aminocentesis. Complications included 3 failures, 14 blood-stained samples, 2 cases of labor occuring within 24 hours after amniocentesis, and 1 maternal abdominal wall hematoma. There was no cases of perinatal morbidity or mortality. It is proposed that this is a safe method of abdominal amniocentesis for L/S determination in late pregnancy.

Influence of gestational age on prediction of fetal lung maturity by fluorescence polarization of amniotic fluid.

Compared are the amniotic fluid fluorescence polarization values and the neonatal outcomes of 201 pregnant women who delivered from 28 through 37 weeks of gestation within 48 hours of the fluorescence polarization determinations. Thirty-five neonates developed hyaline membrane disease. The corresponding fluorescence polarization values ranged from 0.275 to 0.391. Eight of those 35 tests results were less than 0.325. The predictiveness of the method was studied using different threshold fluorescence polarization values. At the authors' own threshold of less than or equal to 0.325, the overall predictive value was as follows: false mature predictions: 6.2%, false immature predictions: 62.5%, sensitivity: 77.1%, and specificity: 72.8%. However, the false mature prediction rate was 21 to 40% from week 28 through week 33 versus 3.4 to 5.8% from week 34 through week 37, depending on the selected cutoff fluorescence polarization value. The sensitivity and specificity before, at, or after week 34 were significantly different at all tested fluorescence polarization values (P less than .05 to P less than .01) with the exception of the sensitivity at 0.310 and at 0.316 (P = .057). Caution is advised against relying on the fluorescence polarization method to predict fetal lung maturity at least before 34 weeks of gestation.

Determination of amniotic fluid microviscosity at body temperature: a predictor of fetal lung maturity.

One of the most convenient ways to determine fetal lung maturity is by measuring the fluorescence polarization (P) of the amniotic fluid at room temperature. With sensitivity fixed on 100%, specificity is relatively unsatisfactory. The present study compared the predictive power of fluorescence polarization measured at temperatures 25C (P25), 37C (P37), and 40C (P40) among 195 consecutive samples tested at both 25C and 37C, with a subgroup of 86 samples tested also at 40C. A better separation between the results for fetuses with and without hyaline membrane disease is attained at P37, demonstrated by a greater mean standardized distance (distance between P values for those patients with and the mean P value for those patients without hyaline membrane disease in unit of standard deviation of the latter; 1.597 +/- 0.528 for P25 versus 2.332 +/- 0.591 for P37). Fixing the sensitivity at 100%, the specificity of P25 and P37, were 68.9 and 94.9%, respectively; a highly significant difference (P less than .001). The specificity of P40 was 90.5%, lower than that of P37. P37 is the best predictor and adding either P25 or P40 does not improve the prediction of lung maturity. It is concluded that P37 should replace P25 as the definite index for fetal lung maturity.

Acute polyhydramnios recurrent in successive pregnancies. Management with multiple amniocenteses.

A patient with acute polyhydramnios in two successive pregnancies is described. In both this case and the only previously reported similar one, management by frequent transabdominal removal of relatively small amniotic fluid volumes was associated with prolongation of pregnancy and a living infant, suggesting that multiple amniocenteses can improve the otherwise hopeless prognosis associated with acute polyhydramnois.

Prediction of fetal lung maturity by amniotic fluid fluorescence polarization, L:S ratio, and phosphatidyl glycerol.

The relation of amniotic fluid fluorescence polarization (FP) to fetal lung maturity was examined in 186 pregnancies terminating within 48 hours of the fluid collection. Among the 9 babies who developed hyaline membrane disease (HMD), 8 were associated with FP values of 0.340 or more, and 1 had an FP value of 0.329. In 95 of these patients, the lecithin:sphingomyelin (L:S) ratio and the presence or absence of phosphatidyl glycerol (PG) were also determined. All 9 infants with HMD had L:S ratios less than 2.00 and no PG detectable in the amniotic fluid. Using an FP value of 0.325 or less, an L:S ratio of 2.00 or more, and the presence of PG as criteria for lung maturity, FP, L:S ratio, and PG did not differ significantly in the number of false predictions of HMD. Each test detected some mature infants who would have been incorrectly classified by at least 1 of the other tests. The status of all infants born at 33 weeks' gestation or later who did not develop HMD would have been correctly predicted by FP, L:S ratio, or both. These 3 tests, therefore, are complementary and can be used in combination to reduce the number of false predictions of HMD.

Clinical evaluation of the quantitative foam stability index test.

The foam stability index (FSI) test for amniotic fluid is a quantitative test that uses ethanol as the antifoaming reagent; it presents values in terms of the highest ethanol volume fraction that will permit stable foam to occur. In this study the authors report on FSI tests results in terms of neonatal outcome in a total of 208 pregnancies in which fluids were obtained within 3 days of delivery. The authors noted a total of 27 cases of hyaline membrane disease (HMD) in their population. All 27 had FSI values of 0.47 or less, whereas 119 of the 181 patients without HMD had FSI values of 0.48 or above. The risk of HMD's occurring was calculated for 4 groups of FSI values. They were as follows: 1) FSI values less than or equal to 0.43 (62%); 2) FSI values of 0.44 and 0.45 (23%); 3) FSI values of 0.46 and 0.47% (14%); and 4) FSI values greater than 0.48 (0%). Comparable evaluations of the lecithin:sphingomyelin (L:S) ratio procedure performed on the same specimens revealed no apparently improved diagnostic reliability. In addition, in several cases of intrauterine growth retardation with normal neonatal respiratory status in which the L:S ratios were less than 1.5, the FSI test correctly predicted fetal lung maturity (FSI greater than or equal to 0.48). The authors conclude that the FSI test has sufficient diagnostic reliability to be considered as a sensitive and specific assay of fetal pulmonary maturation.

Evaluation of the FELMA microviscosimeter in predicting fetal lung maturity.

A new, rapid technique for determining fetal lung maturity, the FELMA, was tested against the standard lecithin/sphingomyelin (L/S) ratio in predicting hyaline membrane disease (HMD). The FELMA was tested on 236 samples, 154 of which were compared with the L/S ratio; 102 neonates were delivered within 48 hours. There was a significant correlation between methods ( r = 0.47). No neonate with a mature FELMA score developed HMD. Of 5 neonates with HMD, 2 had mature L/S ratio in predicting lung immaturity, providing a rapid result without the necessity of thin-layer chromatography.

Optimization of diagnostic discrimination applied to the amniotic fluid lecithin/sphingomyelin ratio.

An unrecognized disparity frequently separates the intuitive reliance placed on laboratory information by those who produce it and those who use it. To harmonize these dissimilar perceptions requires quantitative measures of the information contained in laboratory data. The assay of the lecithin/sphingomyelin ratio in amniotic fluid is used as an example to analyze the discriminatory ability of a test. This assay can be optimized from the different viewpoints of sensitivity, specificity, diagnostic effectiveness or value. In each case test results are interpreted in the light of different factors and so the optimal decision threshold to separate positive from negative results may vary. Appreciation of this concept would endow the interpretation of laboratory tests with the same flexibility traditionally available to other clinical information.

Inspired gas temperature in ventilated neonates.

The warming and humidification of inspired gases for ventilated neonates are routine. There are no data on the temperature of the gas at the airway opening in ventilated neonates. Is the inspired gas temperature at the airway opening, as expected and set on the humidifier, around 37 degrees C? We aimed to measure temperature at the airway opening and compare this with the circuit temperature. This was an observational study in a neonatal intensive care unit. Twenty-five mechanically ventilated infants were studied. All had humidifiers with chamber temperature set at 36 degrees C and the circuit temperature set at 37 degrees C. Two temperature probes were inserted and rested at the circuit-exit and at the airway opening, and temperatures were measured for 2 min in each infant. At this time, the circuit temperature was also noted. The mean (SD) temperature at the airway opening in infants nursed in incubators was 34.9 (1.2) degrees C, compared with radiant warmers where the mean (SD) was 33.1 (0.5) degrees C. The mean (SD) difference in temperature from the circuit temperature probe to the airway opening was greater under radiant warmers, with a mean (SD) drop of 3.9 (0.6) degrees C compared with a mean (SD) drop of 2.0 (1.3) degrees C in the incubators. In conclusion, the temperature at the circuit temperature probe does not reflect the temperature at the airway opening. Inspired gas temperatures are lower than the expected 37 degrees C with the normal circuits and usual humidifier settings.