Biomedical subjects
Publications and source records attributed to S Arnon.
Two historical cohorts (1993-1994 and 2001) of preterm infants ventilated for respiratory distress syndrome were compared. Dexamethasone administration fell from 22% to 6%. Chronic lung disease in survivors rose slightly from 13% to 17%, and mortality fell from 21% to 15% (other causes). The effect of restriction of dexamethasone use on chronic lung disease and mortality remains to be seen.
We describe a patient diagnosed with lethal perinatal hypophosphatasia with a unique clinical presentation of convulsions that responded to vitamin B6. Genomic DNA sequence analysis of the tissue-nonspecific alkaline phosphatase (TNSALP) gene revealed two missense mutations: a G-to-A transition resulting in a Glu to Lys at codon 274 (E274K), and a G-to-C transversion resulting in a Gly to Arg at codon 309 (G309R). The first mutation was maternally transmitted and was previously characterized as a moderate one, whereas the latter was paternally transmitted and has not been previously reported. Phenotype/genotype correlation indicates that G309R is a deleterious mutation that can lead to seizures and a lethal outcome, as was demonstrated in our patient.
Currently, preterm labour is treated with tocolytic agents and prenatal steroids until the 34th week of gestation only. Our objective in this study was to assess this practice. Seven-year records of all preterm infants born in our institution at 34--36 weeks of gestation, were evaluated retrospectively. All babies, born in singleton well-dated pregnancies, without maternal, medical or obstetric complications, and by normal vaginal delivery, were included. Their length of hospital stay and perinatal complications were compared across gestational age groups of 34, 35 and 36 weeks. Of the 207 babies included, statistically significant reductions in the rates of respiratory distress syndrome (15.0% vs. 3.2%), nosocomial sepsis (5.0% vs. 0%) and apnoea of prematurity (11.7% vs. 2.2%), and consequently, in length of hospital stay (16 +/- 2.7 vs. 4 +/- 0.3 days) occurred between 34 and 36 weeks of gestation. The severity of respiratory distress syndrome also declined significantly. The changes were most noticeable after 35 weeks of gestation, and it was concluded that neonatal complications are still prevalent at 34 and 35 weeks. Therefore, we propose that labour should not be induced at 34 and 35 weeks of gestation and that tocolytic agents and maternal prenatal steroids may be considered in preterm labour during this period.
We describe a preterm neonate with documented group B Streptococcus sepsis and associated metabolic acidosis whose lactic acidemia was refractory to conventional sodium bicarbonate therapy but responded well to dichloroacetate treatment.
We determined the levels of circulating bone turnover markers in preterm infants during the first weeks of life. Twenty premature infants (mean gestational age 27+/-2.2 weeks, mean birth weight 894+/-231 g) hospitalized in the neonatal intensive care unit (NICU) at the Meir General Hospital, Israel, participated in the study. Measurements of bone turnover markers were performed at birth, and every week thereafter for an average follow-up of 11.2+/-0.7 weeks. Bone osteoblastic activity was assessed by measurements of circulating osteocalcin, bone-specific alkaline phosphatase (BSAP) and the C-terminal procollagen peptide (PICP) levels. Bone resorption was assessed by measurements of serum levels of the carboxy-terminal cross-links telopeptide of type I collagen (ICTP). All three markers of osteoblastic activity increased markedly and significantly during the first three weeks of life, and then continued to increase gradually until week 10 (p<0.01). Circulating ICTP levels increased in the first week of life and then decreased gradually throughout the follow-up (p<0.01). The study participants were divided into premature infants born at extremely low birth weight (ELBW: <1000 g, n=12) and very low birth weight (VLBW: 1000-1250 g, n=8). Osteocalcin (in weeks 2-5 of life), PICP (weeks 3-5), and ICTP levels (weeks 2-3) were significantly higher in VLBW preterms. These results suggest increased bone formation in premature infants in the first three months of life. The increased bone turnover in VLBW compared to ELBW premature infants may be the result of a generally higher morbidity in ELBW preterm infants in early stages of life.
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Reported herein are the cases of three infants who were born with serious intrathoracic injuries, apparently sustained at the time of the mother's involvement in a motor vehicle accident. The accidents occurred at 26th, 29th and 36th weeks of pregnancy and resulted in minimal injuries to the mothers themselves. The infants were born four weeks, three hours and two days later, respectively. Their injuries were manifested (singly) by hemothorax, pneumothorax and contusion of lung, the latter in a setting of multi-organ trauma. We suggest that chest x-ray, in addition to brain ultrasound, be routinely included in the evaluation of neonates whose mothers were involved in a motor vehicle accident during pregnancy, not excluding cases wherein the mother's injuries were negligible or inapparent and regardless of the time elapsed between accident and delivery.
Perinatal hemochromatosis is a rare disorder with an enormous iron overload in the parenchymal organs, especially the liver, pancreas, heart and endocrine glands. Elements of the reticuloendothelial system are relatively spared. The clinical course is rapidly progressive and the disease is invariably fatal. Several siblings are described in the literature. Herein, we describe one pair of full siblings affected by the disease, wherein the clinical presentation was hydrops. We suggest that hemochromatosis should be considered in the differential diagnosis of hydrops fetalis.
The aim of this randomized, double-blind, placebo-controlled trial was to assess the short-term effect of a topical glucocorticoid (budesonide 600 mu g twice daily) vs. placebo administered by metered dose inhaler (MDL) and spacer (Aerochamber MV15) directly into endotracheal tube of intubated infants for 7 days. Twenty preterm infants (mean birthweight, 1,030 g; mean gestational age, 27.3 weeks)who still needed assisted ventilation at 14 days of age were randomly assigned to receive budesonide (n=9) or placebo (n=11) and completed the study. The primary outcome was the need for mechanical ventilation after 7 days of treatment. Other outcome variables included ventilator settings, blood gases, serum cortisol levels, and bronchoalveolar lavage inflammatory cell counts. No ventilated infant was extubated during the study period. The treatment group showed significant improvements in mean peak inspiratory pressure, ventilator efficiency index, and (A-a) oxygen difference. There were no changes in the placebo group. Serum cortisol levels and bronchoalveolar lavage cell counts did not change significantly during study period. There was no difference in side effects between the groups. This trial demonstrates that topical budesonide administered by MDL and Aerochamber produces clinical improvement in ventilated preterm infants, without glucocorticoid side effects.
A 4-year-old boy presented with developmental delay, aggressive behavior, and incoordination. His EEG showed a diffuse encephalopathy. At age 10 he developed convulsions and severe migraine-like headaches. Muscle wasting, arreflexia, and lactic acidemia following exercise were noted. Electromyography was myopathic and nerve conduction studies revealed a peripheral neuropathy. Muscle biopsy demonstrated variation in fiber size and an excess of lipid droplets. He than had several stroke-like episodes and periods of unconsciousness, associated with severe metabolic acidosis. Muscle cytochrome C oxidase was abnormally low. This boy displayed the classical clinical and biochemical features of MELAS syndrome, namely Mitochondrial myopathy, Encephalopathy, Lactic Acidosis, and Stroke-like episodes. Treatment included carnitine, vitamin C, vitamin K, riboflavin, coenzyme Q10, and corticosteroids. He died at the age of 14 years following an episode of seizures, coma, and gastrointestinal hemorrhage. This is the first reported case of MELAS syndrome in Israel.
To evaluate the clinical significance of eosinophilia in newborn infants, 261 admissions to the neonatal unit over a 12-month period were studied retrospectively; 33 babies with eosinophilia (> 1.0 x 10(9)/l) were studied. Clinical and laboratory data for the first month of life were compared, where available, between gestational age-matched pairs with and without eosinophilia. Of the 33 babies with eosinophilia, 23 were > 26 weeks' gestation and all had age-matched controls; 10 were < or = 26 weeks' gestation but had no appropriate gestational age-matched controls. Babies > 26 weeks' gestation with eosinophilia had a significantly higher number of septic episodes than controls: 20 of 23 versus 4 of 23. All 10 babies < or = 26 weeks' gestation with eosinophilia developed sepsis. Infections with gram-negative organisms and necrotizing enterocolitis occurred only in babies who developed eosinophilia. In 5 babies no cause for the eosinophilia was found. In conclusion, eosinophilia in the newborn is usually explainable and is most often associated with infection.
There is increasing evidence that bronchodilators are effective in ventilator dependent preterm infants. The effects of single doses of salbutamol (400 micrograms), ipratropium bromide (72 micrograms), and placebo (four puffs) given by metered dose inhaler and spacer (MDIS) were examined in 10 ventilated preterm infants, with a mean birth weight of 800 g at a postnatal age of 1 week, who were suffering from respiratory distress syndrome. The agents were each given in an open, random design. Blood gases were measured and ventilatory efficiency index (VEI) and arterial/alveolar oxygen tension ratio (PaO2/PAO2) were calculated five minutes before and 30 minutes after administration. Heart rate and mean arterial blood pressure were noted. The mean PaO2 improved by 0.61 kPa and 0.69 kPa after salbutamol and ipratropium bromide, respectively and these changes were significantly greater than the 0.5 kPa fall seen with placebo. The mean arterial carbon dioxide tension fell by 0.98 kPa after salbutamol and 0.59 kPa after ipratropium bromide. After both salbutamol and ipratropium bromide, VEI improved significantly (by 23% and 20% respectively) but there was no significant change in the PaO2/PAO2, suggesting that respiratory mechanics and not ventilation/perfusion balance had improved after a single dose of bronchodilator. We conclude that both salbutamol and ipratropium bromide given by MDIS have useful short term effects in ventilator dependent neonates with respiratory distress syndrome. Precise dose regimens and long term effects remain to be worked out.
It has been shown that inflammatory cells in the newborn lung are fetal in origin, whereas those in the amniotic fluid are maternal. In order to explore the relationship between fetal amnionitis and neonatal pneumonitis, we collected paired samples of gastric aspirate within 2 hours of birth, and bronchoalveolar lavage fluid within 24 hours of birth from intubated preterm infants. Leukocyte counts in bronchoalveolar lavage fluid correlated with the duration of membrane rupture (r = 0.68, P = 0.0001). There was a high degree of correlation between leukocyte counts in the two fluids (r = 0.86, P = 0.0001). The factors responsible for this association are unknown.
Neither the origin of leucocytes in the premature newborn airway nor their relationship to perinatal factors has been adequately determined. In order to sample airway cells, modified bronchoalveolar lavage was performed on 74 intubated infants of < 32 weeks' gestation and < 24 hours of age. Cells were counted, stained and, in a small separate group of six infants, four boys and two girls, probed for the Y chromosome with suitable control samples. Perinatal risk factors for increased airway cellularity were analysed by multiple regression. Premature rupture of membranes of more than 24 hours' duration was independently associated with increased numbers of airway leucocytes (n = 74). More than 90% of airway leucocytes from four boys with pulmonary inflammation were positive for the Y chromosome indicating that the cells were of fetal rather than maternal origin.
The aim of this study was to determine the effect of surfactant treatment on the number and distribution of inflammatory cells in bronchoalveolar lavage fluid (BALF) from mechanically ventilated preterm infants over the first week of life in relation to the subsequent development of chronic lung disease (CLD). The study included 25 babies who received surfactant on clinical grounds and 29 babies of similar severity who did not. BALF was collected on days 1, 3, 5, and 7 after birth. Cell counts were performed and differentials were calculated on 300 cells. CLD was equally common in both treatment groups. Of the 54 infants, 29 (53%) who developed CLD had a higher incidence of patent ductus arteriosus and air leak and needed a higher concentration of inspired oxygen on the fifth and seventh days of life. Babies who developed CLD had more polymorphonuclear leucocytes and fewer macrophages on days 5 and 7 than those who recovered. Surfactant treatment was associated with a higher total white cell count on day 3. Between days 3 and 7, macrophage numbers were higher in surfactant treated babies, whatever the pulmonary outcome. This data suggests that CLD was associated with persistence of high numbers of polymorphonuclear leucocytes in BALF at the end of the first week. Surfactant treatment caused a persistent increase in macrophage numbers. The association between persistent neutrophilia and CLD was unaffected by surfactant treatment.
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.
Delivery of drug aerosols to the lungs of ventilated neonates by metered dose inhaler and spacer (Aerochamber) and ultrasonic nebuliser (Pentasonic) was assessed using sodium cromoglycate. The mean proportion of a known intratracheal dose of sodium cromoglycate excreted in the urine of four intubated infants was 37.5%. After assuming that 38% of the sodium cromoglycate aerosol reaching the neonatal lung will be excreted in the urine, three puffs (15 mg) delivered by metered dose inhaler and spacer resulted in a pulmonary dose of 258 micrograms (1.7%, n = 7). A dose of 20 mg (4 ml) sodium cromoglycate ultrasonically nebulised over five minutes into the inspiratory limb of a standard ventilator circuit produced a pulmonary dose of 257 micrograms (1.3%, n = 7). Of two in vitro lung models assessed, a combination of filter and neonatal test lung was superior to a multistage impactor in estimating the in vivo pulmonary sodium cromoglycate dose delivered by metered dose inhaler and spacer (243 micrograms v 1740 micrograms).
Two groups of intubated newborn babies were studied to determine the clinical effects of interrupted bronchoalveolar lavage (BAL) by suction catheter (S-BAL) and the similarities to adult fibreoptic BAL of fractional processing of sequential lavage fluid (BALF). Both groups were lavaged by two aliquots of 1 ml.kg-1, instilled via a blindly placed suction catheter, wedged on two separate insertions through the right main bronchus. In 14 infants, (sequential lavage group), BALF aliquots were analysed separately. There were no differences in the volumes recovered or total cell counts between the first and second BALF aliquots. Where cell morphology was visible (n = 11), the percentage of macrophages, but not the absolute number, increased in the second BALF aliquot (p less than 0.01). BALF urea and epithelial lining fluid volume estimated by urea dilution were similar between the two aliquots (n = 8). In a separate group (blood gas group), vital signs were recorded in 10 infants undergoing S-BAL. At 1 min after lavage there was a rise in mean arterial blood pressure (39 vs 49.5 mmHg, p less than 0.05) and a fall in transcutaneous oxygenation (10.6 vs 7.5 kPa, p less than 0.05). Recovery was present at 3 min post-S-BAL, but mean blood pressure remained elevated (39 vs 45 mmHg, p less than 0.05) and transcutaneous oxygen continued to be lower when compared to baseline values (10.6 vs 9.2 kPa, p less than 0.05). S-BAL of intubated infants appears to sample both the proximal and distal airways and results in changes in vital signs similar to routine non-selective endotracheal suctioning.