Faculty Bibliography

During the past 20 years, advances in drug formulations and innovative routes of administration have been made. Our understanding of drug transport across tissues has increased. These changes have often resulted in improved patient adherence to the therapeutic regimen and pharmacologic response. The administration of drugs by transdermal or transmucosal routes offers the advantage of being relatively painless.(1,2) Also, the potential for greater flexibility in a variety of clinical situations exists, often precluding the need to establish intravenous access, which is a particular benefit for children. This statement focuses on the advantages and disadvantages of alternative routes of drug administration. Issues of particular importance in the care of pediatric patients, especially factors that could lead to drug-related toxicity or adverse responses, are emphasized.

Numerous prescription and nonprescription medications are currently available for suppression of cough, a common symptom in children. Because adverse effects and overdosage associated with the administration of cough and cold preparations in children have been reported, education of patients and parents about the lack of proven antitussive effects and the potential risks of these products is needed.

OBJECTIVE: To determine whether the extent of cervical dilatation at cesarean delivery affects the subsequent vaginal birth after cesarean (VBAC) rate. METHODS: Relevant records of the index pregnancy (group I) were reviewed for cervical dilatation at cesarean delivery, oxytocin use, indication, neonatal weight, and epidural use. The records of the subsequent pregnancy (group II) were reviewed for successful VBAC rates, neonatal weight, oxytocin, and epidural use. RESULTS: There were 1917 patients in the study. The indications for cesarean in group I were malpresentation (5.1%), fetal distress (14.9%), and arrest disorders (80%). In group II, the VBAC success rates were 73% for previous malpresentation and 68% for previous fetal distress. In those with previous cesarean deliveries for arrest disorders with cervical dilatation at 5 cm or less, the VBAC success rate was 67%. It was 73% for 6-9 cm dilatation and 13% for the fully dilated group (P < .05). CONCLUSIONS: Patients who attempt a VBAC may be counseled that a cesarean delivery at full dilatation is associated with a reduced chance of a subsequent successful VBAC

Because of an increasing number of reports of adverse reactions associated with pharmaceutical excipients, in 1985 the Committee on Drugs issued a position statement(1) recommending that the Food and Drug Administration mandate labeling of over-the-counter and prescription formulations to include a qualitative list of inactive ingredients. However, labeling of inactive ingredients remains voluntary. Adverse reactions continue to be reported, although some are no longer considered clinically significant, and other new reactions have emerged. The original statement, therefore, has been updated and its information expanded.

Objective: Tn order to determine if tocolytic agents affect fetal ventricular function, we used the combined ventricular shortening fraction, an echocardiographic index of fetal cardiac function to evaluate fetuses whose mothers were being treated for preterm labor. Study design: A group of 30 patients diagnosed with preterm labor and eligible for tocolytic therapy were the subjects of this prospective non-randomized cohort study. Sixteen patients were treated initially with subcutaneous terbutaline, five with intravenous ritodrine, and nine with intravenous magnesium sulfate. All were later maintained on oral therapy with either terbutaline or ritodrine. Each fetus acted as its own control. Each was studied before treatment, while on a clinically therapeutic intravenous or subcutaneous regimen, during oral therapy, and after birth. The in utero evaluations included a biophysical profile, umbilical artery Doppler waveform study, and an M-mode tracing of ventricular wall motion generated from a four-chamber view of the heart to assess the end diastolic and the end systolic dimensions. The combined ventricular shortening fraction was then calculated as (end diastolic - end systolic)/end diastolic x 100%. Multiple analysis of variance was used to compare means over time for each variable. Means between groups were compared using the two-tailed Student's t test; P = 0.05 was utilized. Results: No significant change was noted in the mean combined ventricular shortening fraction of fetuses who had been exposed to tocolytic agents, all of whom had normal studies. The mean combined ventricular shortening fraction pretreatment was 34.8%, as compared with 33.9% in patients treated with beta-mimetics. Those treated with MgSO4 had an improved mean combined ventricular shortening fraction of 37.9%. This change was not statistically significant. Doppler and biophysical profiles were normal, and preterm labor was successfully arrested in all cases. Conclusion: In this small pilot study short ten treatment with commonly utilized tocolytic agents did not appear to affect fetal ventricular function

The beta-sympathomimetic oral tocolytic ritodrine can cause maternal tachycardia and hypotension, and may cross the placenta. A new echocardiographic technique has been developed to explore fetal and placental ritodrine effects. Values in 76 healthy historic controls were compared to 18 studies in 16 patients performed while receiving stable oral ritodrine therapy, measured both at baseline and 30 minutes after a dose. Data collected included maternal pulse and blood pressure (BP), fetal cerebral and umbilical Doppler waveforms, and fetal heart rate. A new index of fetal myocardial contractility, combined ventricular shortening fraction, was derived from two-dimensionally directed M-mode. Maternal pulse and BP, fetal heart rate and heart size, and all Doppler indices were normal, without demonstrable dose-response effects. In the control subjects, combined ventricular shortening fraction fell with increasing gestational age (combined ventricular shortening fraction = -0.27 estimated gestational age + 49; r = 0.27; P < or = 0.02; standard error of the estimate, 11%). However, combined ventricular shortening fraction in ritodrine patients was abnormally decreased in 72% of cases. The mean index in normal subjects was 43 +/- 5%, but in ritodrine patients it was only 31%. We conclude that a history of premature labor or oral ritodrine, or both, is associated with reduced shortening fraction. Since there was no change in placental resistance, cerebral hypoxia, fetal heart rate, or heart size (preload), then low shortening fraction may be due to increased fetal systemic vascular resistance (BP) or decreased myocardial contractility

Cord blood-derived CD34+ cells have proved superior to adult marrow or elicited peripheral blood in ex vivo cell and progenitor expansion. In addition, cord blood-derived cells with a phenotype and function of early stem cells (e.g., long-term culture-initiating cells) can be expanded in vitro in the presence of a combination of cytokines by 15- to 20-fold over 7-14 days. These observations suggest that ex vivo expansion of cord blood CD34+ cells will permit improved engraftment of adults and will prove effective in retroviral-mediated gene transfection of early stem cell populations.