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Biomedical subjects

M Perlman

Publications and source records attributed to M Perlman.

At least 37 records · Page 2Linked to original sources

Bilirubin beyond the blood-brain barrier.

We evaluated the utility of recording neural signals, such as auditory brainstem responses, as potential new criteria for treatment of neonatal jaundice. Findings from recent studies of auditory brainstem responses and behavior of jaundiced infants reinforce the notion that asymptomatic and even symptomatic neurotoxicity caused by bilirubin may occur relatively frequently at relatively low serum bilirubin concentrations. Evidence suggests that this is transient and reversible. Whereas current criteria for the prevention of kernicterus are based on the idea that bilirubin entry to the CNS should be averted, the existence of transient subclinical and clinical bilirubin-induced neurotoxicity suggests that the focus of prevention might be shifted to events beyond the blood-brain barrier. With the use of "finer tools" to detect neurotoxicity, it may be possible to recognize a prior stage of neurotoxicity, described here as "transient subclinical bilirubin-induced neurotoxicity." Recordings of neural signals might be used as either predictors of kernicterus or as immediately available "outcomes" or end points with which biochemical predictors (serum bilirubin and "unbound" bilirubin concentrations) might be correlated, to determine their relative value as predictors of entry of bilirubin to the CNS. It is suggested that the results of studies to determine the relative risks associated with the various predictive criteria, namely, a prospective cohort analysis, may not be available for many years and that randomized controlled trials of new criteria for exchange transfusion are even further removed from reality.

Animals

Predicting survival of infants of birth weight less than 801 grams.

The likelihood of survival to 28 days of life was determined retrospectively for 106 infants weighing less than 801 g at birth. Multiple logistic regression analysis revealed that birth weight and inspired oxygen fraction made an independent contribution to the prediction of survival at 8 h of age (predictive accuracy 76%). At 16 and 24 h of age, body temperature, pH, and the presence of spontaneous breaths were the independent variables predicting survival (predictive accuracy 79%). Of 37 infants with calculated chances of survival of less than 50% at 16 h, 29 died (predictive accuracy 78%). Seven of the remaining eight infants who survived "against the odds" either died later of chronic lung disease or had severe handicapping complications by 3 months of age. These predictions are first approximations and are not intended for use in making decisions about patient management.

Body Temperature

A simple method for the estimation of glomerular filtration rate by gentamicin pharmacokinetics during routine drug monitoring in the newborn.

Assessment of the glomerular filtration rate (GFR) in the newborn is often imprecise because of difficulties in urine collection and because the plasma creatinine level, the traditional marker of renal function, is influenced by many factors in this age group. Gentamicin is given to most preterm infants for suspected or proved sepsis. This drug is eliminated almost entirely by the kidney and its rate of elimination parallels the GFR. We calculated gentamicin pharmacokinetic parameters (t1/2, volume of distribution, and clearance) from three consecutive concentration-time points (trough, peak, and next trough levels) in 38 newborn infants. Creatinine clearance was measured by the conventional method. Both t1/2 (r = 0.74; P less than 0.001) and gentamicin clearance (r = 0.77; P less than 0.001) correlated well with measured creatinine clearance. There was no correlation between these variables and urine output. Gentamicin elimination t1/2 and clearance are useful indices of GFR in the newborn infant and can be easily calculated during routine therapeutic drug monitoring.

Creatinine

Diagnosis and therapy of necrotizing tracheobronchitis in ventilated neonates.

From January 1983 to September 1984 our neonatal ICU (NICU) treated eight endotracheally intubated infants who had suspected airway obstruction characterized by hypercarbia dissonant with severity of lung disease and difficulty in ventilation with lack of chest movement, both on conventional intermittent mandatory ventilation and high-frequency oscillation. Bronchoscopic removal of necrotic tissue was possible in six infants, two of whom survived. Bronchoscopy showed desquamation of epithelial surfaces, leaving encrusted exudations considered to be characteristic of necrotizing tracheobronchitis (NTB). The four nonsurvivors of bronchoscopy and one of the infants not submitted to bronchoscopy had NTB confirmed at autopsy. NTB was not associated with any specific lung disease, humidifier, or ventilator. The autopsy frequency of NTB during this period was 5 per 160 NICU admissions. A separate chart review of unselected autopsied cases in 1981 and 1982 showed that 12 of 284 neonates admitted to the NICU had NTB. NTB appears to be a rediscovered condition related to endotracheal intubation and mechanical ventilation using high mean airway pressures.

Bronchitis

Evaluating a filter device used for intermittent intravenous drug delivery to newborn infants.

Injection of aminoglycosides into a filter chamber was compared with retrograde injection into i.v. tubing for delivery of intermittent drug dosages at low infusion rates in neonates. In 50 infants receiving gentamicin sulfate and 21 receiving amikacin sulfate for at least two days by retrograde i.v. infusion, peak and trough concentrations of the drugs were obtained. A subsequent dose was administered using the filter device, and peak and trough concentrations were obtained. For each infant, the difference between trough and peak concentration (delta C) was compared for the two methods. In vitro testing for gentamicin concentration was performed using the same infusion systems (10 trials for each system). For both in vivo and in vitro testing, the infusion flow rate was 10 mL/hr. For infants receiving gentamicin, delta C was greater for the filter device in 32, greater for retrograde infusion in 13, and equal in 5. The mean gentamicin delta C was significantly greater for the filter chamber method than for retrograde infusion. The in vitro studies showed significantly better gentamicin recovery with the filter device than with retrograde infusion. For amikacin, delta C was greater for the filter device in 15 infants, but the mean amikacin delta C was not significantly different for the two methods. At low flow rates commonly used in infants, the infusion system using the filter device was equal to or superior to retrograde infusion for ensuring complete delivery of intermittent drug doses.

Amikacin

Combined noninvasive assessment of the patent ductus arteriosus in the preterm infant before and after indomethacin treatment.

Fifteen preterm infants who weighed 0.7 to 2.0 kg and had clinical evidence of a patent ductus arteriosus (PDA) were studied by combined 2-dimensional and Doppler echocardiography before and after the administration of indomethacin. In 10 patients the PDA was widely patent at the time of the study and in 5 the lumen was narrow. In this latter group, the PDA was narrow at the pulmonary artery end in 2 patients, in the middle in 2 patients and at the aortic end and the middle in 1 patient. After the administration of intravenous indomethacin, the PDA closed completely in 12 patients and constricted in 3. The patterns of closure could be documented in those in whom serial studies were performed. In 3 patients, closure occurred after a single dose of indomethacin, in 3 after 2 doses and in the rest after a full course of 3 doses. Doppler interrogation at the aortic and pulmonary artery end of the PDA demonstrated the shunting patterns and provided a reliable assessment of patency after the ductal lumen was outside the range of lateral resolution following constriction. In no case did the PDA reopen after the course of indomethacin. This combined approach is a reliable method of assessing a PDA before and after a course of indomethacin. It should provide the means to answer many of the questions regarding the effect of various manipulations on the PDA in the preterm infant.

Ductus Arteriosus, Patent

Mechanical vibration and sound levels experienced in neonatal transport.

Exposure of neonates to sound and to mechanical vibration was measured while transferring the neonates to a regional referral unit by ambulance and by rotary wing and fixed wing aircraft. Recordings were made during different phases of each type of transportation and were analyzed later. In the nursery, sound levels ranged from 72 to 74 dBA (A-weighted decibel level) (77 to 81 dB), while in transit, levels were higher at 78 to 99 dBA (90 to 110 dB), depending on the means of transport. Vibration was measured in the horizontal and vertical axes relative to the neonate in different frequency ranges. The vibration acceleration magnitude ranged from 0.4 m/sq s to 5.6 m/sq s, depending on the axis and type of transport; the maximum obtained was in rotary wing transport. When compared with adult tolerance levels, both sound and vibration exposure of the neonate are high and potentially hazardous. Further evaluation of vibration stress and means of attenuating sound and vibration in transport infant incubators is desirable to enhance the safety of transported infants.

Aircraft

Aminoglycoside-related nephrotoxicity in the premature newborn.

The nephrotoxicity of gentamicin and amikacin was compared during presumed sepsis in 107 premature neonates. To examine the possibility that nephrotoxicity was directly associated with the clinical conditions of "sepsis," a control group of 26 chloramphenicol-treated newborns was also studied. Two markers of proximal renal tubular injury, N-acetyl-beta-glucosaminidase (NAG) and beta 2-microglobulin, were measured in 6-hr aliquots of urine. Because urine creatinine excretion increased with postconception age, markers were expressed in terms of excretion rate rather than per milligram of creatinine. The NAG excretion rate was significantly higher in gentamicin-treated patients (138 +/- 10 U/min, mean +/- SE) than in amikacin-treated patients (85 +/- 7 U/min) but did not differ between patients treated with amikacin and those treated with chloramphenicol (81 +/- 11 U/min). Excretion of beta 2-microglobulin did not differ among the three patient groups. We conclude that amikacin may be less nephrotoxic than gentamicin in the premature newborn.

Acetylglucosaminidase

Selective bronchial intubation for pulmonary emphysema.

Two neonates with respiratory distress syndrome developed unilateral pulmonary interstitial emphysema causing mediastinal shift and compressive atelectasis. Treatment with contralateral bronchial intubation for five days proved to be life saving.

Bronchi

Changes in auditory brainstem responses in hyperbilirubinemic infants before and after exchange transfusion.

Auditory brainstem responses (ABR) were evoked, before and after exchange transfusion, in an effort to determine whether hyperbilirubinemia is associated with acute effects on brainstem function of neonates. Nine full-term infants with hemolytic disease received exchange transfusion for conventional serum bilirubin concentration indications (mean 22.3 +/- 1.4 mg/dL). In three infants, wave-absence before exchange transfusion was followed by appearance of the waves after exchange transfusion. Other significant alterations observed in the group after exchange transfusion were increase of wave amplitudes and reduction of interpeak latencies (brainstem transmission time 5.80 +/- 0.36 ms after exchange transfusion compared with 6.25 +/- 0.30 ms before exchange transfusion, P less than 0.001). These improvements are considered to have been brought about by removal of bilirubin from the body and from the brainstem during exchange transfusion. Acute brainstem toxicity appears to occur in a percentage of infants with hyperbilirubinemia at serum levels commonly seen in clinical practice. These changes appear to be rapidly reversible with exchange transfusion.

Bilirubin

Effects of indomethacin on digoxin pharmacokinetics in preterm infants.

Indomethacin is commonly coadministered with digoxin for the treatment of patent ductus arteriosus (PDA) in preterm infants. The combination of digoxin that is eliminated almost exclusively by the kidney and indomethacin, which tends to reduce renal function, has potential hazards. We report 11 preterm infants (gestational age 25-33 week) treated with digoxin for PDA in whom a standard indomethacin therapy (mean of total dose = 0.32 mg/kg) resulted in a significant elevation of serum digoxin to potentially toxic levels (from 2.2 +/- 0.7 ng/ml to 3.2 +/- 0.7) (P less than 0.001). This phenomenon correlated well with decreased urine output (from 86 +/- 34 ml to 43 +/- 24 per 24 hour) (P less than 0.001) following indomethacin. No significant change was found in serum creatinine concentration pre- and post-indomethacin. Digoxin half-life was significantly prolonged (mean 97 +/- 17 hour) following indomethacin therapy as compared with an age matched control group (mean half-life 43 +/- 19 hour) (P less than 0.05). Our data suggest that when indomethacin is added to digoxin therapy, the digoxin dosage should be reduced by 50% until urine output and digoxin serum levels can be better assessed.

Digoxin

Auditory nerve-brainstem evoked responses in hyperbilirubinemic neonates.

On the basis of the known predilection of the auditory brainstem pathway for bilirubin toxicity, we have examined auditory brainstem responses of neonates during the period of hyperbilirubinemia. The auditory brainstem responses of 24 infants with serum bilirubin values between 15 to 25 mg/dL were compared with the responses of 19 infants without hyperbilirubinemia, who had similar gestational and postnatal ages. Wave IV-V complex was absent in at least one recording of 10/24 jaundiced infants, whereas wave complex IV-V was consistently present in all of the 19 infants without hyperbilirubinemia (P less than .001). Jaundiced infants also had prolonged brainstem transmission time (P less than .01) which reflected increased latency at both lower and upper brainstem levels. The above changes were rapidly reversed in the majority of instances. Neonatal jaundice was associated with significant transient aberrations of auditory brainstem responses, suggestive of a transient brainstem encephalopathy. This evidence of bilirubin entry to the brain at conventionally acceptable serum concentrations raises questions about current concepts of the mechanism of transfer of bilirubin across the blood-brain barrier.

Bilirubin