Combined general and epidural anesthesia for a child with alagille syndrome: a case report

Alagille syndrome (syndromic paucity of interlobular bile ducts) is the most common form of familial intrahepatic cholestasis. We describe the perioperative management of a pediatric patient with Alagille syndrome undergoing ileal exclusion and the specific issues associated with epidural anesthesia with this syndrome.     

Myocardial performance index in evaluation of acute right ventricular myocardial infarction

The goal of this study was to evaluate the role of Doppler time interval-derived myocardial performance index (MPI) in the setting of acute right ventricular myocardial infarction (RVMI). Inferior myocardial infarction is accompanied by RVMI in over a third of cases. We do not have easily applicable noninvasive tools for reliably quantifying the right ventricular (RV) dysfunction in RVMI and to serially follow alterations. Clinical and echocardiography data of all acute inferior myocardial infarction (IMI) admissions (n = 135) to our referral teaching institute were prospectively collected for the study. After exclusions, study group comprised of 36 patients with RVMI diagnosed by >/=1 mm ST segment elevation in V3R-V5R of right-sided ECG and 63 patients without RVMI constituted the control group. All patients underwent echocardiography within 24 hours of admission. Normal range of MPI for our laboratory was estimated from 50 age-matched healthy subjects. RV MPI was elevated to a mean of 0.53 +/- 0.22 in RVMI (Normal MPI 0.20 +/- 0.05, P-value < 0.001). IMI without RVMI did not elevate MPI significantly (0.21 +/- 0.17, P-value NS). Repeat MPI estimation in 11 RVMI (7 thrombolyzed) patients after 5 days showed dramatic reduction (0.23 +/- 0.12, P-value < 0.001). This reduction was noted irrespective of thrombolysis. RV MPI >/= 0.30 has high sensitivity (82%) and specificity (95%) for the diagnosis of RVMI in the presence of acute IMI. MPI can reliably diagnose RV infarction. It can be used to quantify right ventricular dysfunction and assess acute improvements in RV function.     

Partial characterization of endothelial FGF receptor functional domain by monoclonal antibody VBS-1

Polypeptide growth factors mediate their cellular responses by binding to and activating specific cell surface receptors. Monoclonal antibody (MAb) VBS-1, produced against native fibroblast growth factor receptor-1 (FGFR-1), inhibited the binding of fibroblast growth factor-2 (FGF-2) to its receptor on coronary venular endothelial cells (CVECs) as determined by 125I-FGF-2 Scatchard analysis and [3H]thymidine uptake assays (ED50 = 80 ng/mL). Enzyme studies demonstrated that MAb VBS-1 binds to a protein epitope. Proteolytic mapping of the CVEC-FGFR established that a 52 kDa doublet contained the FGF binding site and the MAb VBS-1 antigenic epitope. N-glycanase digestion suggested the presence of a 50 kDa core protein for the CVEC-FGFR. Tunicamycin treatment resulted in the loss of expression of the core protein and the mature receptor, indicating the importance of CVEC-FGFR n-linked glycosylation. By Northern blot analysis, it was determined that CVECs express fgfr-1 and not fgfr-2. VBS-1 recognized FGFR-1 (140 kDa) and crossreacted weakly with FGFR-2 (135 kDa). Using a combination of affinity crosslinking, proteolytic mapping and Mab VBS-1 binding studies, we have located the FGF binding site near the NH2-terminal domain of the receptor close to the highly acidic box.     

Psychostimulants in preschool children with attention-deficit/hyperactivity disorder: clinical evidence from a developmental disorders institution

OBJECTIVE: To examine psychostimulant response in preschool children with attention-deficit/hyperactivity disorder (ADHD) in an outpatient child psychiatry clinic (housed within a developmental disorders institution) over 3, 12, and 24 months of treatment. METHOD: A systematic retrospective chart review was conducted for 27 preschool children with ADHD who were started on psychostimulants between the ages of 3 and 5 years, inclusive. Two child and adolescent psychiatrists reviewed each chart independently, using the Clinical Global Impressions (CGI) scale to rate the severity of illness and global improvement and the Side Effects Rating Form to rate side effects. RESULTS: Over 24 months, psychostimulants were stopped in three children (11%) because of side effects and concomitant psychotropic medications were added in seven children (26%). The CGI severity-of-illness ratings showed a significant effect of time over 3, 12, and 24 months of psychostimulant treatment (all p values < .0001). Rate of response was 74% at 3 months and 70% at 12 and 24 months. Side effects were mostly mild and occurred in 63% of the children at 3 months, 41% at 12 months, and 29% at 24 months. CONCLUSIONS: The findings suggest that preschool children with developmental disorders respond to psychostimulants but need close monitoring because of frequent side effects. Inasmuch as the study participants were recruited from a child psychiatry clinic housed within a developmental disorders institution and had a high rate of developmental disorders, the findings may not generalize to other preschool children with ADHD.     

Phase I clinical trial of all-trans-retinoic acid with correlation of its pharmacokinetics and pharmacodynamics

 A phase I trial of all-trans-retinoic acid (ATRA) was conducted to establish the maximum tolerable dose (MTD) of ATRA given once daily to patients with solid tumors. Cancer patients for whom no standard therapy was available were treated with ATRA once daily. Doses were escalated in cohorts of at least three patients. The pharmacokinetics of ATRA were assessed on day 1 for all patients and weekly for 31 patients who received doses of ≥110 mg/m² per day. Patients were followed for toxicity and response. Correlations of toxicity frequency and grade with pharmacokinetic parameters were sought. In addition, correlation of changes in ATRA pharmacokinetics with the concentration of ATRA metabolites in plasma were sought. A total of 49 patients received ATRA at doses ranging from 45 to 309 mg/m² per day. Hypertriglyceridemia was dose-limiting at 269 mg/m² per day. Other frequent toxicities included mucocutaneous dryness and headache. With chronic dosing, plasma ATRA concentrations fell in 59% of patients. Stable, low, or variable [ATRA] were seen in 16%, 6%, and 16% of patients respectively. Age, gender, smoking, or concurrent medication did not correlate with the pharmacokinetic pattern. Severe toxicities tended to occur with initial peak [ATRA] of ≥0.5 μg/ml (1.7 μM), and the toxicity frequency did not change if [ATRA] decreased with continued dosing. No consistent change in 4-oxo-ATRA or retinoid glucuronide concentrations was observed with decreases in plasma [ATRA]. The recommended once-daily ATRA dose is 215 mg/m², although significant interpatient variability is observed in toxicity and plasma retinoid concentrations. Although not statistically significant, more frequent and severe toxicity tended to occur in patients with higher plasma peak ATRA concentrations. Other factors, such as responses at target tissues, may be at least as important as the plasma ATRA concentration in predicting toxicity and/or response. Received: 7 January 1996 / Accepted: 24 June 1996     

Validated HPLC method for determination of PAT-5A, an insulin sensitizing agent, in rat plasma

A high performance liquid chromatographic method for the determination of PAT-5A (a potent insulin sensitizer) using DRF-2095 (a thiazolidinedione) as internal standard (I.S.) is described. A 1:1 v/v ethylacetate and dichloromethane solvent mixture was used for extraction of PAT-5A from plasma. A Kromasil KR100-5C18-250A, 5 microm, 4.6 x 250 mm SS column was used for the analysis. Mobile phase consisting of sodium dihydrogen phosphate (pH 4.0, 0.05 M) and methanol mixture (25:75, v/v) was used at a flow rate of 1.0 ml/min. The eluate was monitored using a UV detector set at 345 nm. Ratio of peak area of analyte to I.S. was used for quantification of plasma samples. Using this method the absolute recovery of PAT-5A from rat plasma was > 90% and the limit of quantification was 0.05 microg/ml. The intra-day relative standard deviation (RSD) ranged from 2.19 to 4.98% at 1.0 microg/ml, 1.05 to 3.68% at 10.0 microg/ml and 3.14 to 5.08% at 50 microg/ml. The inter-day RSD were 1.6, 2.24 and 1.54% at 1, 10 and 50 microg/ml, respectively. The method was applied to measure the plasma concentrations of PAT-5A in pharmacokinetic and bioavailability studies in male Wistar rats.