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Biomedical subjects

M Perlman

Publications and source records attributed to M Perlman.

At least 19 recordsLinked to original sources

Association between duration of neonatal hospital stay and readmission rate.

OBJECTIVE: A recent rapid decrease in the duration of neonatal hospital stay in Ontario, Canada, enabled us to study the association between healthy infants' age at neonatal hospital discharge and subsequent readmission rates. DESIGN: (1) Population-based and (2) single hospital-based retrospective studies. SETTING AND STUDY POPULATION: (1) A total of 920,554 healthy infants with a birth weight of 2500 gm or more, born in Ontario from 1987 to 1994. (2) Infants with a birth weight of 2500 gm or more, born during the same period, and readmitted before 15 days from home to the Hospital for Sick Children for jaundice or dehydration. MEASUREMENT: Duration of neonatal stay in the hospital and readmission rates were measured, and diagnostic codes were analyzed. Severity of illness was evaluated in infants readmitted to our hospital. RESULTS: In Ontario the mean length of stay decreased from 4.5 days to 2.7 days (p = 0.000), and the readmission rate during the first 2 weeks of life increased from 12.9 to 20.7 per 1000 (p = 0.000). Increased rates of readmission were most marked for jaundice and dehydration. The infants readmitted to our hospital had evidence of increased severity of illness as indicated by higher serum bilirubin and sodium concentrations. Two deaths occurred in infants with hypernatremic dehydration, one in 1992-1993 and another in 1993-1994. CONCLUSIONS: In Ontario, shorter neonatal hospital stay was associated with increased readmission rates for conditions that may not give rise to symptoms or signs on days 1 to 3 of life. In our hospital the severity of jaundice and dehydration in readmitted infants increased. The severity-of-illness data raise the question of whether shorter neonatal hospital stay of apparently healthy infants is always safe. Decisions to discharge infants should be based on rigorous evaluation of individual infants.

Analysis of Variance

Amiloride delays the ischemia-induced rise in cytosolic free calcium.

An increase in cytosolic free calcium (Cai) has been shown to occur early during ischemia in perfused rat, ferret, and rabbit hearts. It has been proposed that this increase in Cai may occur as a result of exchange of Nai for Cao, which occurs as a result of an increase in Nai arising from exchange of Nao for H+i. The latter exchange is stimulated by the intracellular acidification that occurs during ischemia. To test this hypothesis, we examined Cai, Nai, ATP, and pHi during ischemia in rats in the presence and absence of 1 mM amiloride, a Na-H exchange inhibitor. Cai was measured using 19F nuclear magnetic resonance (NMR) of 1,2-bis(2-amino-5-fluorophenoxy)ethane-N,N,N',N'-tetra-acetic acid (5F-BAPTA)-loaded rat hearts. Nai was measured using 23Na NMR, and the shift reagent 1,4,7,10-tetraazacyclododecane-N,N',N",N"'-tetramethylenephosph onate (Tm[DOTP]-5) was used to separate Nai and Nao. ATP and pH were determined from 31P NMR measurements. During 20 minutes of ischemia, amiloride did not significantly alter the ATP decline but did significantly attenuate the rise in Nai and Cai. After 20 minutes of ischemia, time-averaged Cai was 1.0 +/- 0.2 microM (mean +/- SEM) in amiloride-treated hearts compared with 2.3 +/- 0.9 microM in nontreated hearts. After 20 minutes of ischemia, Nai in the untreated heart was threefold greater than control, whereas in the amiloride-treated heart, Nai was not significantly different from control. These data are consistent with the involvement of Na-Ca exchange in the rise in Cai during ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Amiloride

Informational needs of parents of sick neonates.

Sixty-one parents of 43 neonates in a neonatal intensive care unit were interviewed within 3 days of their first conference with the neonatologist to assess their needs for medical information. The conference with the physician and the interview with the investigator were audiotaped. Information given by the physician and information recalled by the parents was categorized and rated by the investigator. The physicians gave very detailed information about diagnosis in 77% of cases whereas 39% of the parents recalled diagnostic information in great detail. Respective percentages for prognosis were 16 and 33; for current management (eg, investigation, therapy), 28 and 66; and for cause of illness, 16 and 18. The statistical significance of the differences between the very detailed information int he physician-parent conferences and in the parent-investigator interviews was, by category, less than .002, less than .041, less than .004, and not significant, respectively. Information in the respective categories was described as "most helpful" by 20%, 67%, 90%, and 8% of parents. All but one of the parents stated that they wanted the whole truth. Physician uncertainty in providing information was significantly associated with severity of illness. It is concluded that while parents wanted information in all categories, they paid most attention to that relating to management. Physician-parent discordances with respect to information about management, diagnosis, and prognosis suggest directions for future investigation of the optimal content of information for parents in this context.

Adult

A new system for location of endotracheal tube in preterm and term neonates.

A randomized, controlled trial was conducted to evaluate a new noninvasive system for placement of the endotracheal tube, based on a magnetic field interference-sensing technique. Seventy-two neonates treated by the standard technique were compared with 70 treated by the new system (TRACH MATE), with radiographic localization as the standard. As judged by the author(s) on the morning after the intubation, correct initial placement was achieved in 69 (78%) of 88 intubations using the new system, compared with 71 (66%) of 107 using the standard technique (Fisher's Test, one-tailed, P = .044). Repositioning was actually done in 23 (26%) of 88 TRACH MATE intubations, compared with 42 (39%) of 107 standard intubations (Fisher's test, one-tailed; P = .037). Intubation of the right main bronchus occurred in 7 standard intubations, but in none of the TRACH MATE intubations (Fisher's test, one-tailed; P = .014). Endotracheal tube position (high, low, or appropriate) was correctly determined by TRACH MATE in 77 (90%) of 85 intubations; the position was not recorded on three occasions. No differences in the number of complications (eg, unplanned extubations, distal displacement, subglottic stenosis) were found between the two groups. It is concluded that the TRACH MATE technique is superior to the standard clinical method in initial placement of the endotracheal tube.

Humans

Dissociation constants for dihydrofolic acid and dihydrobiopterin and implications for mechanistic models for dihydrofolate reductase.

The dissociation constants (pKa) for the pteridine ring system of dihydrofolate (H2folate) have been redetermined, and those for dihydrobiopterin (H2biopterin) have been determined. Determination of the pKa for N5 of H2folate is complicated by the low solubility and instability of H2folate at pH 2-4, and other complicating factors. The initial rate of absorbance change due to degradation is a maximum at pH 2.5, and the products depend on the oxygen concentration: under aerobic conditions, (p-aminobenzoyl)glutamic acid and 7,8-dihydropterin-6-carboxaldehyde are major products. H2Biopterin is much more soluble and more stable at low pH. For protonation of N5, the pKa is 2.56 +/- 0.01 for H2biopterin and 2.59 +/- 0.03 for H2folic acid. Spectrophotometric determination of the pKa for the N3-O4 amide group of H2folate is subject to serious errors when a wavelength between 220 and 235 nm is used. These errors arise from the pH-dependent absorbance of mercaptoethanol often present in the preparation. The amide group has a pKa of 10.41 +/- 0.04 in H2biopterin and 10.85 +/- 0.04 in H2folate. The redetermined value for the pKa of N5 of H2folate has implications for mechanistic models for dihydrofolate reductase, and revised kinetic constants have been calculated for one model.

Biopterins

Reduced platelet counts in neonatal respiratory distress syndrome.

Platelet counts were studied in preterm infants with the respiratory distress syndrome (RDS), excluding patients with significant perinatal and postnatal hypoxia. Counts fell to a nadir on day 4 (p less than 0.000). Exploratory analysis indicated that severity of RDS (levels of FiO2 and mean airway pressure), airleak syndrome, grade of intraventricular hemorrhage (IVH) and low platelet count on day 1 were correlated with low platelet count on days 4 and 5. Further analysis by stepwise removal of each variable demonstrated statistically that FiO2 exerted a unique influence on the change in platelet count between day 1 and days 4/5 (p less than 0.002). It is concluded that the severity of RDS is strongly associated with the fall in platelet count in the first few postnatal days. The effect of IVH on platelet count may be secondary to the effect of the RDS.

Age Factors

Neonatal autoimmune thrombocytopenia: role of high-dose intravenous immunoglobulin G therapy.

High-dose intravenous immunoglobulin G (IVIgG) therapy results in a rapid reversal of thrombocytopenia in over 80% of children with acute immune thrombocytopenic purpura (ITP). Comparable results were observed in eleven infants with an analogous condition, neonatal autoimmune thrombocytopenia (NATP), who received IVIgG (2 g/kg body weight) administered alone (n = 6) or in combination with steroids (n = 5). The median platelet count pre-IVIgG therapy was 25 X 10(9)/l (range 5 to 74 X 10(9)/l). The overall response rate to IVIgG therapy, administered alone or in combination with steroids was 75% (12 of 16 treatment episodes). A good response to therapy was defined as an increase in the platelet count to greater than or equal to 50 X 10(9)/l and at least twice the pre-treatment value at 48 h after completion of the IVIgG infusion. The rapid and generally excellent response to IVIgG therapy in infants with NATP suggests that this treatment approach should be considered as first-line therapy for severely thrombocytopenic infants with this self-limiting but potentially serious disorder.

Autoimmune Diseases

Characterization of prostaglandin production in amnion-derived WISH cells.

This study was undertaken to characterize prostaglandin production and its regulation in the human amnion-derived WISH cell line. Epidermal growth factor, tumor growth factor-alpha, tumor growth factor-beta, human interleukin-1, tumor necrosis factor, phorbol 12-myristate 13-acetate, phorbol 12,13-dibutyrate, 4 alpha-phorbol 12,13 didecanoate, and dexamethasone were tested for their ability to modulate prostaglandin production in WISH cells. Quantitatively, the major prostaglandin produced in WISH cells was prostaglandin E2. Treatment with epidermal growth factor, tumor growth factor-alpha, tumor necrosis factor, interleukin-1, phorbol 12,13-dibutyrate, and phorbol 12-myristate 13-acetate resulted in a concentration-dependent stimulation of WISH cell prostaglandin E2 production; tumor growth factor-beta and the inactive phorbol ester analog 4 alpha-phorbol 12,13 didecanoate had no effect. Dexamethasone treatment resulted in concentration-dependent inhibition of prostaglandin E2 production by WISH cells. WISH cells responded in a qualitatively similar manner to that previously observed in primary cultures of human amnion with the exception of the response to dexamethasone. On the basis of the findings of this investigation, we suggest that WISH cells may be a useful model for studying some but not all aspects of the regulation of arachidonic acid release and prostaglandin E2 formation in amnion. WISH cells may also be used to evaluate the mechanisms that link regulation of immune function and arachidonic acid metabolism.

Adjuvants, Immunologic

High-frequency oscillation in the rescue of infants with persistent pulmonary hypertension.

High-frequency oscillatory ventilation (HFOV) was used to treat 41 infants with persistent pulmonary hypertension of the newborn (PPHN). Of the 37 patients who showed early improvement on HFOV, three died. The remaining 34 patients demonstrated, within one hour of the switchover to HFOV, a rise in mean arterial/alveolar oxygen tension ratio (PaO2/PaO2) from 0.093 +/- 0.041 (SD) to 0.132 +/- 0.051 (p less than .001), and a fall in mean PaCO2 from 42 +/- 10 to 34 +/- torr 9 (p less than .01). Mean airway pressure (Paw) fell significantly (p less than .01) within 12 h. The mean duration of conventional mechanical ventilation before starting HFOV was longer in 13 patients who developed bronchopulmonary dysplasia (BPD) than in 21 non-BPD patients (44.7 +/- 32.3 vs. 19.1 +/- 15.6 h, p less than .002), as was the duration of exposure to Paw greater than 15 cm H2O during that treatment mode (31.8 +/- 21.3 vs. 9.5 +/- 6.0 h, p less than .001). HFOV is often effective in the treatment of patients with PPHN, and early initiation of this type of mechanical ventilation may be associated with a reduced incidence of BPD.

Birth Weight

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