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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

The impact of early obstetric discharge on newborn health care.

The impetus for shorter hospital stay of mother and newborn infant after delivery is based on economic constraints and parental preference. Earlier published studies did not demonstrate any increase in morbidity rate with shorter stay, but these studies were limited by methodologic flaws and biases that limited the validity and generalizability of the conclusions. More recent studies showed that readmission rates increased with shorter stay and that the severity of illness of readmitted infants may have increased. In addition, the interpretation of current newborn screening tests may not be applicable when performed prior to early discharge. In light of recent changes in neonatal hospital length of stay, a careful review and update of current guidelines and practices for newborn care are required.

Humans↗

High cervical spinal cord injury in neonates delivered with forceps: report of 15 cases.

OBJECTIVE: To inform obstetricians of a serious complication of forceps rotations of 90 degrees or more--high cervical spinal cord injury in neonates. METHODS: We reviewed the obstetric aspects of 15 cases of high cervical spinal cord birth injury diagnosed during 1982-1994 at two tertiary-care children's hospitals in Canada. RESULTS: The common feature in all cases was a forceps cephalic delivery, almost always a rotation of 90 degrees or more from the occipitoposterior or occipitotransverse position. CONCLUSION: High cervical spinal cord injury in neonates is a rare but specific complication of forceps rotation.

Birth Injuries↗

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↗

Secular changes in the outcomes to eighteen to twenty-four months of age of extremely low birth weight infants, with adjustment for changes in risk factors and severity of illness.

OBJECTIVES: To analyze secular changes in the rates of death and of major impaired outcome in surviving outborn infants who weighted < or = 800 gm at birth and were admitted in 1980 to 1989, with adjustment for changes in risk factors and severity of illness around the time of birth; and to identify changes in these factors that might explain changes in outcomes. DESIGN: Retrospective cohort study with follow-up to a minimum of 18 months of postterm age. After preliminary screening, multivariate models of association between risk/severity of illness factors and outcomes were constructed, validated, and used to adjust outcomes (death and major impairment to 18 to 24 months of age). SETTING: Regional neonatal intensive care unit for referral of "outborn" infants. PATIENTS: Two hundred eighty-seven consecutively admitted infants who weighted < or = 800 gm at birth (97% follow-up). RESULTS: The death rate during the 1980s did not fall significantly (p adjusted for risk factors = 0.115). The major impairment rate fell (odds ratio, 0.24 (95% confidence interval, 0.10, 0.60); p = 0.002, adjusted for delivery route and respiratory failure measures), mainly because of a reduced rate of blindness, not attributable to cryotherapy. The risk factors that improved and were possibly related to the reduced impairment rate were blood pH and glucose concentration, and serum sodium concentration in the first 48 hours of life. CONCLUSIONS: Despite an increasing selection for referral of less mature and more severely ill outborn babies near the "limit of viability," and despite more aggressive care, the rate of major impairment fell significantly during the 1980s. This trend was enhanced by adjustment for severity of illness. The fall was attributable to a reduced rate of blindness, and was associated with evidence of improved control of physiologic balance after birth.

Apgar Score↗

Surfactant replacement in neonates with early chronic lung disease.

OBJECTIVE: To study the effect of a single dose of exogenous bovine surfactant on oxygen and ventilatory requirements of neonates with early chronic lung disease. STUDY DESIGN: Prospective pilot study. SETTING: Three regional neonatal intensive care units. METHODS: Infants 7 to 30 days old with birth weights less than 1500 g were eligible if they required a fraction of inspired oxygen (FIO2) of more than 0.4, had stable ventilatory requirements for 24 hours before study entry, and showed diffuse haziness on chest radiographs. Those with patent ductus arteriosus or active infection or those receiving steroid therapy were excluded. After treatment with the surfactant, differences in FIO2 and the ventilator efficiency index were analyzed using the Wilcoxon signed rank test. RESULTS: Ten patients were recruited. Median values (range): birth weight, 693 g (530 to 1100 g); gestation, 25 weeks (24 to 27 weeks); and postnatal age at study entry, 13 days (9 to 30 days). The FIO2 decreased significantly between 0 and 1 hour after surfactant administration, from a median (range) of 0.67 (0.47 to 0.88) to 0.39 (0.28 to 0.63). This effect was sustained for 24 hours (median FIO2, 0.36). Although the FIO2 subsequently increased to 0.49 (range, 0.35 to 0.88) at 72 hours, it was significantly lower than that entry before the study. There was a trend toward an increase in the ventilator efficiency index at 24 and 48 hours. CONCLUSIONS: A single dose of surfactant is effective in reducing oxygen requirements in neonates with early chronic lung disease. Surfactant replacement may be useful adjunctive therapy in these neonates.

Chronic Disease↗

Spinal cord injury at birth: diagnostic and prognostic data in twenty-two patients.

OBJECTIVES: To establish criteria, evident soon after birth, that predict long-term outcome of neonates with spinal cord injury (SCI) at birth. DESIGN: Retrospective case-series. SETTING: Five Canadian regional neonatal tertiary care centers. PATIENTS: Consecutive samples of patients referred to five centers for a total of 22 subjects, in whom SCI was diagnosed during life. Sites of lesions were above the fourth cervical vertebrae (n = 14), at the fourth cervical to the fourth thoracic vertebrae (n = 6), and at the thoracolumbar region (n = 2). MEASUREMENTS AND MAIN RESULTS: All 14 patients with upper cervical SCI had cephalic presentations, whereas all 6 patients with cervicothoracic SCI had breech presentations (p < 0.0001). The site and extent of lesion were best diagnosed by clinico-imaging correlations. Ultrasonography appeared to be the most useful imaging study. In patients with upper cervical SCI who had no coexistent central nervous system abnormality associated with early death, long-term outcome in survivors (dependency on mechanical ventilation and on aids for upper limb activity and for ambulation) was best predicted by age when breathing was first observed and by rate of recovery of limb motor function in the first 3 months. The presence of breathing movements on day 1 (n = 2) was associated with mild disability. The absence of breathing movements on day 1 and little or no recovery of motor function in the first 3 months was associated with permanent total dependency on mechanical ventilation and severe quadriplegia (n = 5). Apnea on day 1 and intermediate recovery rates in the first 3 months was associated with variable long-term prognoses (n = 3).

Birth Injuries↗

Changing survival and impairment rates at 18-24 months in outborn very low-birth-weight infants: 1984-1987 versus 1980-1983.

Outcomes at 18-24 months corrected age of very low-birth-weight infants admitted to our Neonatal Intensive Care Unit in 1984-1987 (period 2) were compared with the outcomes of infants admitted in 1980-1983 (period 1) (total 1357 infants). In the 500-750-g birth-weight subgroup, the survival rate increased from 32 to 54% (p = 0.002). Rates of moderate and severe impairment at 18-24 months (neurosensory deficit, or Bayley corrected mental developmental index < or = 68) in this subgroup decreased from 41 to 15% (p = 0.005), and in those without severe impairment, mean mental Bayley scores in periods 1 and 2 were 84 +/- 18 and 90 +/- 16, respectively (p = 0.20). Analysis after exclusion of small-for-gestational-age infants gave similar results. In the small-for-gestational-age infants of birth weight 500-750 g, the survival rate increased but the impairment rate was unchanged between periods. It is concluded that outcomes improved in 1984-1987 compared with 1980-1983 only for infants with birth weight of 500-750 g.

Birth Weight↗

Surfactant therapy in full-term neonates with severe respiratory failure.

OBJECTIVE: In light of the paucity of published data on the use of surfactant in full-term infants with respiratory failure due to meconium aspiration syndrome and respiratory distress syndrome, we report our experience with this therapy. Our goal was to explore possible justification for randomized controlled trials of surfactant treatment in similar patients at an earlier, less severe stage of the disease. METHODS: Retrospective consecutive case series of 20 infants with severe meconium aspiration syndrome and 29 infants with severe respiratory distress syndrome who received bovine surfactant between March 1990 and December 1992 in three neonatal intensive care units in a regionalized setting. Outcome of treatment was assessed by comparing changes in several respiratory indices including the oxygenation index, between 4 and 6 hours and 1 and 3 hours before and after the first dose of surfactant. Differences were analyzed using analysis of variance for repeated measures, with treatment and time as co-variates. RESULTS: In the meconium aspiration group the mean oxygenation index decreased from 36 +/- 12 at 1 to 3 hours presurfactant to 24 +/- 14 at 1 to 3 hours postsurfactant (P < .001). In the patients with respiratory distress syndrome the mean oxygenation index fell from 30 +/- 17 at 1 to 3 hours presurfactant to 12 +/- 6 at 1 to 3 hours postsurfactant (P = .0001). Three of 20 patients with meconium aspiration syndrome and 3 of 29 patients with respiratory distress syndrome received extracorporeal membrane oxygenation. CONCLUSIONS: Surfactant therapy in full-term infants with respiratory failure due to the meconium aspiration and respiratory distress syndromes is often effective in improving gas exchange. A randomized controlled trial of surfactant therapy at an earlier stage in the course of the illness should be performed.

Gestational Age↗

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↗