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Biomedical subjects

A Kugelman

Publications and source records attributed to A Kugelman.

At least 19 recordsLinked to original sources

The role of high-dose oral iron supplementation during erythropoietin therapy for anemia of prematurity.

OBJECTIVE: To assess whether a high intake of oral iron would increase the effect of recombinant human erythropoietin (rHuEPO) on hemoglobin synthesis. METHODS: We studied 30 preterm infants (gestational age 29+/-1.8 weeks, birth weight 1161+/-200 g, at age of 28+/-10 days) who were randomly assigned to receive either 8 mg/kg per day (n=15) or 16 mg/kg per day of oral iron during a course of rHuEPO therapy (900 microg/kg per week) for a duration of 4 weeks. Both groups were comparable in regard to clinical and laboratory data at the time of enrollment. RESULTS: rHuEPO caused a significant increase in reticulocyte count in the low- and high-dose iron groups, 17.1+/-5.3 to 34.7+/-9.2 and 16.3+/-3.3 to 42.5+/-5.6 (10(9)/l), respectively (p<0.05). However, in both groups, hematocrit values remained stable at the end of the study as compared to baseline (0.35+/-0.03% vs. 0.30+/-0.03%, 0.35+/-0.05% vs. 0.30+/-0.03%, NS) and in both groups there was a comparable and significant decrease in ferritin level (259+/-109 to 101+/-40 and 168+/-54 to 69+/-38 microg/l, respectively; p<0.01). The rates of bloody stools without any evidence of necrotizing enterocolitis were not significantly different between the two treatment groups (1/15 vs. 4/15, NS). CONCLUSION: We conclude that a higher dose (16 mg/kg per day) of oral iron is not more beneficial when compared to a lower dose (8 mg/kg per day) during rHuEPO therapy for anemia of prematurity. Further studies will define the optimal dosage and route of administration of iron supplementation during rHuEPO therapy.

Administration, Oral↗

Potential role of high-frequency ventilation in the treatment of severe congenital pleural effusion.

Newborns with severe congenital pleural effusions often present with respiratory failure at birth. We describe two premature infants born at 31 and 33 weeks of gestation with bilateral pleural effusions. Both were drained prior to delivery under ultrasound guidance. The first infant had severe bilateral congenital chylothorax with pulmonary hypertension; the second infant had severe nonimmune hydrops fetalis. Both could be adequately oxygenated but failed to respond to conventional mechanical ventilation (CMV) and chest tube drainage, so that CO(2) elimination could not be accomplished. Both infants were successfully treated with high-frequency ventilation (HFV). We suggest that HFV may be of significant value in establishing adequate ventilation in cases of severe congenital pleural effusions.

Adult↗

Selected abstracts

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Journal Article↗

Intrapartum drainage of fetal pleural effusion.

Our objective was to describe our experience with intrapartum thoracocentesis in fetuses with severe bilateral pleural effusion. We describe the outcome of four consecutive cases of fetal pleural effusion due to chylothorax that were managed by intrapartum thoracocentesis. These fetuses were not candidates for pleuro-amniotic shunting either because of the need for prompt delivery (three fetuses) or because of advanced gestational age (one fetus). Thoracocentesis was performed in the operating theatre under ultrasound guidance prior to Caesarean delivery. Gestational age at the time of diagnosis and thoracocentesis ranged between 26-34 weeks and 31-34 weeks respectively. Bilateral thoracocentesis was performed in two fetuses and unilateral in the remaining two fetuses. All four infants were born in a relatively good condition; however, all eventually required intubation, ventilation and chest tubes. Chest tubes were introduced between 2 h and 5 days after delivery in three infants, and immediately after birth in one infant who was hydropic. Two infants survived and are developing normally. One infant died from sepsis following successful pleurodesis and one from aspiration on day 51. Our conclusions are that intrapartum thoracocentesis seems to be a relatively simple procedure, that allows newborns with pleural effusion, to breathe spontaneously or be more easily ventilated. This in turn, reduces the need to introduce chest tubes in an emergency situation.

Drainage↗

The clinical significance of rigors in febrile children.

UNLABELLED: The objective of the study was to evaluate the significance of rigor as a predictor of bacterial infection in hospitalized febrile infants and children. One hundred febrile children with rigor were studied and compared to 334 febrile matched controls without rigor. All underwent clinical evaluation and appropriate laboratory investigations. The patients were then divided into "bacterial" and "non bacterial" infection groups, as defined in the text. It was demonstrated that 66% of the patients with rigor belonged to the bacterial infection group versus 50% in the non-rigor group (P < 0.005). There was a significantly greater yield of positive blood cultures in the patients with rigor (P < 0.04), especially those over the age of 1 year (P < 0.015). The only laboratory examination of potential value as a predictor of bacterial infection in children with rigor was the band count. An absolute band count of more than 1500/mm was significantly more frequent in the rigor group (P < 0.003), and the combination of a rigor and band count of more than 1500 increased the relative risk for a bacterial infection by a factor of 1.35. These data demonstrate that rigor in hospitalized febrile infants or children significantly increase the likelihood of bacterial infection. CONCLUSION: Although the absence of rigors in febrile children does not exclude bacterial aetiology, their presence significantly increase the probability of an infection requiring appropriate workup and a reader institution of antibiotic therapy.

Adolescent↗

Preauricular tags and pits in the newborn: the role of hearing tests.

The aim of this study was to determine the role of audiometry in a group of newborn infants with preauricular tags or pits. During the 2 years of prospective study, 26 infants were born with preauricular tags or pits (5.7 per 1,000 livebirths) and were assessed for hearing impairment by performing behavioural audiometry on day 3 of life and brainstem-evoked response audiometry at 4 months of age. Five infants had associated congenital anomalies (19%). The behavioural audiometry was abnormal in seven infants (27%). The evoked response audiometry was abnormal in 4/23 (17%) newborn infants with isolated tags or pits, and revealed both conductive and/or sensorineural hearing impairment. The incidence of hearing impairment with isolated preauricular tag/pit was significantly higher (p < 0.001) than the incidence reported in preschool children. We conclude that hearing assessment is recommended in the routine evaluation of the newborn with isolated preauricular tags or pits. This policy may facilitate early diagnosis and treatment of hearing impairment in this population.

Audiometry↗

Pulmonary effect of inhaled furosemide in ventilated infants with severe bronchopulmonary dysplasia.

BACKGROUND: When administered parenterally, furosemide, a loop diuretic, results in improved lung compliance and decreased airway resistance in infants with bronchopulmonary dysplasia (BPD). However, furosemide-induced diuresis results in hypokalemia, chloride deficiency, hypercalciuria, nephrocalcinosis, and rickets. In patients with asthma, inhaled furosemide has recently been demonstrated to inhibit the bronchoconstrictive effects of exercise, cold air hyperventilation, and antigen challenge. We hypothesized that inhaled furosemide will result in improved pulmonary mechanics in ventilated infants with BPD and will prevent the systemic complications of parenteral furosemide. OBJECTIVE: To determine the efficacy and safety of a single dose of inhaled furosemide on pulmonary mechanics in infants with severe BPD who are ventilator dependent at 21 days of age. DESIGN AND METHODS: A randomized, double-blind, crossover study was performed on 9 infants with BPD, each serving as his own control. Each patient was randomized to receive an aerosol dose of furosemide (1 mg/kg in 2 mL of saline) or placebo (2 mL of saline) on the first day of the study and the other agent the following day of the study. Pulmonary mechanics were measured before and 1 and 2 hours after the inhalation using the Pulmonary Evaluation and Diagnostics System. RESULTS: Gestational age (mean +/- SEM) was 29 +/- 1 weeks; birth weight was 1.1 +/- 0.1 kg; age at study was 47 +/- 6 days; and weight at study was 1.8 +/- 0.2 kg. There was no significant change in the pulmonary function measurements before treatment and 1 or 2 hours after treatment with either placebo or furosemide. Baseline and 2-hour values were: dynamic compliance (mL/ cm H2O per kilogram): 0.46 +/- .03 to 0.50 +/- .03 (placebo) and 0.50 +/- 0.02 to 0.51 +/- 0.02 (furosemide); dynamic resistance (cm H2O/L per second): 118 +/- 9 to 106 +/- 7 (placebo) and 111 +/- 8 to 105 +/- 7 (furosemide); and tidal volume (mL/kg): 8.6 +/- 0.5 to 8.9 +/- 0.5 (placebo) and 8.9 +/- 0.2 to 9.4 +/- 0.3 (furosemide). CONCLUSION: We conclude that, under the conditions of our study, a single dose of 1 mg/kg inhaled furosemide does not improve the pulmonary mechanics in ventilator-dependent infants with severe BPD.

Administration, Inhalation↗

The parachute reactions in normal and late walkers.

To study the relationship of the parachute responses to the age of independent walking, three groups of infants were prospectively examined: a normal sitting, normal walking group; a late sitting, normal walking group; and a late sitting, late walking group. All other spheres of the neurodevelopmental examination were normal. It was found that when the parachute responses appeared by age 10 months in the late sitting infants, most of them would achieve independent walking by 15 months. A delay in the parachute reaction in these infants predicted a delay in walking.

Child Development↗

Measurement of lung volumes and pulmonary mechanics during weaning of newborn infants with intractable respiratory failure from extracorporeal membrane oxygenation.

Newborn infants with intractable respiratory failure who require extracorporeal membrane oxygenation (ECMO) experience diffuse pulmonary atelectasis shortly after initiation of ECMO. Atelectasis is likely due to the primary lung injury and the reduction of applied inspiratory ventilator pressure when the respirator settings are changed to the "rest settings." These pathophysiologic changes result in a decrease in lung compliance and lung volumes. We hypothesized that improving lung functions observed during ECMO and indicated by an increase in lung volumes will predict successful weaning from ECMO. Sixteen infants (mean +/- SEM: gestational age, 40.3 +/- 0.3 weeks; birth weight, 3.5 +/- 0.1 kg) with meconium aspiration syndrome (n = 13), sepsis (n = 2), and persistent pulmonary hypertension (n = 1) were studied. We measured passive respiratory system mechanics and lung volumes initially during full ECMO support (115 +/- 18 h on ECMO, Study I), and then within 24 h prior to weaning from ECMO (Study II). Respiratory system compliance (Crs), respiratory system resistance (Rrs), functional residual capacity (FRC), and tidal volume (VT) were measured. Prior to Study I lung volumes were too small to be detected. Crs increased between Study I and Study II (0.41 +/- 0.05 to 0.63 +/- 0.05 mL/cmH2O/kg, P < 0.05), and VT increased between Study I and Study II (5.6 +/- 0.6 to 10.4 +/- 0.8 mL/kg, P = 0.0005). FRC increased from 3.6 +/- 1.0 to 7.9 +/- 0.9 mL/kg (P = 0.0001). There was no change in Rrs (88 +/- 8 to 89 +/- 6 cm H2O/L/s, P = 0.9). The combination of Crs > 0.5 mL/cmH2O/kg and FRC > 5 mL/kg was a better predictor (P = 0.0002) of readiness to wean from ECMO than either Crs (> 0.5 mL/cmH2O/kg, P = 0.057) or FRC (> 5 mL/kg, P = 0.007) alone. The combination of FRC and Crs had a sensitivity of 73.3% and specificity of 100% for successful decannulation. We conclude that repeated measurements of FRC and Crs can assess lung recovery and may assist in establishing criteria for successful weaning from ECMO.

Extracorporeal Membrane Oxygenation↗

Comparison of dynamic and passive measurements of respiratory mechanics in ventilated newborn infants.

Pulmonary mechanics may differ in intubated and ventilated infants depending on whether they are measured by a dynamic or passive method. The objective of this study was to compare respiratory mechanics measured by a dynamic technique with those obtained by a single-breath occlusion technique in ventilated newborn infants. Thirty-one preterm and 15 term infants (mean +/- SD: gestational age, 29.3 +/- 2.3 and 39.5 +/- 1.4 weeks; birth weight, 1.2 +/- 0.5 and 3.4 +/- 0.4 kg; postnatal age, 12 +/- 13 and 5 +/- 4 days, respectively) were studied. Flows were measured through a pneumotachometer placed between the endotracheal tube and the ventilator circuit: tidal volume by integration of flow, and airway pressure directly with a pressure transducer. Airway occlusion was performed with a Neonatal Occlusion Valve (Bicore pulmonary monitor) at the end of inspiration, and the following relaxed exhalation was analyzed to give passive respiratory system compliance (Crs) and resistance (Rrs). These values were compared with dynamic respiratory system compliance (Cdyn) and dynamic expiratory resistance (Re) obtained with the PEDS system (P) within 1 hour, without an esophageal balloon and on the same ventilator settings. Dynamic respiratory system compliance and resistance measured with the PEDS and the Bicore systems did not differ significantly and were well correlated. Mean Cdyn (P) values in preterm and term infants were 77% and 77% of Crs; the equation of the regression line was Cdyn = 0.75 Crs + 0.02 and Cdyn = 0.78 Crs - 0.02; and standard error of the estimate (SEE) was 0.2 and 0.3 mL/cmH2O with a correlation coefficient (r) of 0.89 and 0.89 (P < 0.0001), respectively. The mean Re(P) values in preterm and term infants were 68% and 64% of Rrs, and the equation of the regression line was Re = 0.3 Rrs + 63 and Re = 0.5 Rrs + 20, with SEE of 25 and 20 cmH2O/L/sec, and r of 0.65 and 0.69 (P < 0.0001, P < 0.005), respectively. The two methods are non-invasive and were well tolerated. We conclude that passive and dynamic respiratory compliance and resistance measured in intubated infants are highly correlated, although the values measured by the passive technique are higher than those obtained by the dynamic technique.

Airway Resistance↗

Intratracheal pulmonary ventilation versus conventional mechanical ventilation in a rabbit model of surfactant deficiency.

Intratracheal pulmonary ventilation (ITPV) enhances the clearance of CO2 from dead space and lungs by a bias flow of gas administered in the distal trachea. ITPV flow is continuously administered through a separate catheter placed within an endotracheal tube (ETT). After exiting from catheter's tip in the distal trachea, the flow of gas is redirected outward away from the lungs. We hypothesized that, compared with conventional mechanical ventilation (CMV), ITPV may increase minute CO2 clearance (VCO2), reduce the partial pressure of CO2 dioxide in arterial gas (PaCO2), and reduce distal tracheal peak inspiratory pressure (dPIP). We induced surfactant deficiency in 15 adult rabbits by lung lavage with 10 mL/kg normal saline. Animals were ventilated through a double-lumen 4.0 ETT, inserted through a tracheotomy incision. dPIP, distal positive end expiratory pressure, and distal mean airway pressure were monitored, and the mean exhaled CO2 concentration was measured. For ventilator rates (respiratory rate) of 30, 45, and 70 breaths/min, the study included two phases: phase I compared CO2 clearance and PaCO2 between ITPV and CMV using similar ventilatory pressures; phase II evaluated the effectiveness of ITPV in reducing dPIP and tidal volume (Vt), compared with CMV, while maintaining eucapnea. When comparing ITPV and CMV, the following results (mean +/- SD) were achieved at respiratory rate of 30, 45, and 70 breaths/min, respectively. Phase I ITPV resulted in mean percent reduction of PaCO2 by 31.4 +/- 10%, 37.1 +/- 9.7% and 38.3 +/- 9%; mean percent increase in VCO2 by 61.3 +/- 29%, 56 +/- 23, and 98 +/- 40%, compared with CMV. Phase II ITPV resulted in mean percent reduction of dPIP by 35.5 +/- 14%, 38 +/- 10.8%, and 37.2 +/- 13.7%, and mean percent reduction in Vt by 34.7 +/- 12.9%, 36.4 +/- 15%, and 52.7 +/- 10.7%, compared with CMV. The changes in PaCO2, VCO2 (phase I), and dPIP and Vt (phase II) were all significantly more than 25% (p < 0.05). Oxygenation and pH were not significantly different between ITPV and CMV. We conclude that, in a surfactant deficiency rabbit model, ITPV is an efficient mode of assisted ventilation that increases CO2 clearance and reduces ventilator pressures required for adequate ventilation. We speculate that ITPV can minimize lung barotrauma associated with mechanical ventilation.

Animals↗

Quinone-induced oxidative stress elevates glutathione and induces gamma-glutamylcysteine synthetase activity in rat lung epithelial L2 cells.

Glutathione (GSH) is one of the most important physiological antioxidants involved in detoxification of hydrogen peroxide and lipid hydroperoxide. Previous studies have shown that cells can maintain and even increase cellular GSH content in response to sublethal oxidative stress. We hypothesized that gamma-glutamylcysteine synthetase (gamma GCS), the rate-limiting enzyme in de novo GSH synthesis, could be induced by oxidative stress. Rat lung epithelial L2 cells were challenged with 2,3-dimethoxy-1,4-naphthoquinone (DMNQ), generates O2.- and H2O2 continuously through redox cycling. Exposure of confluent L2 cells with sublethal doses of DMNQ caused sustained elevation of cellular GSH levels over a 24-h period (to 2.5-fold with 10 microM). DMNQ caused increases in gamma GCS activity (70% at 24 h with 10 microM), the gamma GCS catalytic heavy subunit (gamma GCS-HS) protein level, and gamma GCS-HS mRNA content (approximately 4-fold after 6 h with 10 microM). The elevation of gamma GCS-HS mRNA by DMNQ was eliminated by co-incubation with actinomycin D. Nuclear run-on experiments demonstrated that the transcriptional rate of the gamma GCS-HS gene was increased by 3- or 6-h exposure to 10 microM DMNQ. Our results suggested that the induction of de novo GSH synthesis by naphthoquinone-induced oxidative stress is associated with the transcriptional activation of the gamma GCS-HS gene and the subsequent elevation in gamma GCS activity. Unlike simpler quinones, DMNQ cannot form a GSH conjugate. Thus, the induction of gamma GCS-HS gene transcription does not require formation of an electrophile-glutathione conjugate.

Animals↗

Relationship between the parachute reactions and standing and walking in normal infants.

Assumption of the vertical position and independent walking are potentially hazardous motor milestones in the developing infant. It has been presumed that the parachute reactions evolved to protect infants from injury during this developmental stage. To determine the relationship between the appearance of the upper and lower parachute reactions and the developmental milestones of unsupported standing and independent walking, 190 normal infants were prospectively studied. The upper parachute reaction was found to precede the lower by less than a month (mean age of appearance: 8.9 and 9.2 months, respectively). More than one-half of the cohort achieved standing without either the upper (49%) or lower parachute reaction (57%); however, no independent walking occurred without the upper parachute reaction, and only 2 of 190 infants (1%) walked independently without the lower parachute reaction. Onset of walking occurred about 4 months after the appearance of the upper parachute reaction. The significance of these findings is discussed.

Accidental Falls↗

gamma-Glutamyl transpeptidase is increased by oxidative stress in rat alveolar L2 epithelial cells.

The tripeptide glutathione (GSH) is used by cells to detoxify hydroperoxides, produced during oxidative stress, and is consumed in the process. Previous studies have indicated that cells can be protected against oxidative stress by extracellular GSH through its degradation catalyzed by the exoenzyme gamma-glutamyl transpeptidase (gamma GT) and its de novo synthesis within the cytosol. We hypothesized that gamma GT would be increased as part of the adaptation of cells to oxidative stress. We examined whether oxidative stress could increase gamma GT activity, protein, and mRNA in a lung epithelial cell line (L2). Cultures were subjected to H2O2-mediated toxicity by 15 min of exposure to the redox cycling quinone, menadione. Menadione (50 microM) caused an initial decrease (27 +/- 9% of baseline after 15 min) in intracellular GSH, followed by resynthesis to levels significantly higher than baseline (335 +/- 40% after 24 h, P < 0.001). This elevation was prevented by acivicin, a gamma GT inhibitor. Menadione also caused a dose-dependent increase in gamma GT enzymatic activity (715 +/- 125% of control at 24 h after 15 min of exposure to 100 microM menadione, P < 0.001) that was prevented by actinomycin D. Western blot analysis indicated increased levels of gamma GT protein with increasing menadione. A concentration-dependent increase in gamma GT-mRNA was also observed. Previous investigation has demonstrated that an increase in gamma GT activity enhances the capacity of cells to utilize extracellular GSH. The findings presented here are consistent with a role for gamma GT in cellular adaptation to oxidative stress.

Animals↗

Reduction of respiratory system resistance of rabbits with surfactant deficiency using a novel ultra thin walled endotracheal tube.

The ultra thin walled, two-stage endotracheal tube (UTW-TS-ETT) is very flexible, nonkinking, and has a widened extralaryngeal portion. The UTW-TS-ETT has a greater ID/OD (internal diameter/outer diameter) ratio than a comparable standard endotracheal tube (ST-ETT) because of its thinner wall: 0.2-0.25 mm in UTW-TS-ETT, compared to 0.55-0.8 mm in ST-ETT. The authors hypothesized that in an animal model of lung disease, significant reductions in respiratory system resistance (Rrs) of 30-40% would be achieved using the UTW-TS-ETT, compared to Rrs achieved with the comparable ST-ETT. This study compared the pulmonary mechanics of rabbits (N = 17, body weight 3.4-4.7 kg) before and after induction of surfactant deficiency, using either ST-ETT (OD 4.9 mm, ID 3.5 mm) or UTW-TS-ETT (OD 5.0 mm, ID 4.6 mm). Animals were sedated, paralyzed, and ventilated by an ETT placed through a tracheotomy incision. Surfactant deficiency was induced by lavaging the lungs with normal saline (10 ml/kg). Pulmonary mechanics were measured on identical ventilator settings for each ETT used at baseline and at 45 min after lavage. Compared to ST-ETT, UTW-TS-ETT reduced Rrs by 50.6 +/- 8.7% in normal lungs (significantly more than 40%; p < 0.01), and by 41.47 +/- 16.2% in surfactant deficient lungs (significantly more than 30%; p < 0.05). Tidal volume increased with UTW-TS-ETT in all animals but did not achieve statistical significance. The UTW-TS-ETT did not induce significant changes in respiratory system compliance, PaO2, PaCO2, or pH. It is concluded that UTW-TS-ETT significantly reduces Rrs in rabbits with either normal lungs or with surfactant deficient lungs. This novel ETT may be beneficial for ventilated patients with increased Rrs, by effecting a decrease in Rrs and thus reducing the work of breathing and improving ventilation efficiency.

Animals↗