Biomedical subjects
Publications and source records attributed to R K Chang.
Although the cardiac effects of tacrolimus (FK506) have not been well documented, clinical cases of children on FK506 who developed hypertrophic obstructive cardiomyopathy have been reported. We report 2 cases of marked concentric hypertrophy of the left ventricular myocardium found at autospy in children on FK506.
Variation in moisture content of the capsule shells either due to the change of storage conditions or the moisture transfer between the capsule shell and its contents may lead to undesired physical properties, such as capsule brittleness and stickiness. DMP 504, a developmental bile-acid sequestrant, is a strongly basic anion-exchange polymer which contains randomly distributed primary, secondary, tertiary, and quaternary amine groups in their hydrochoride salt form. The alkylammonium groups which comprise this polymer form a random network containing a high level of branching and a low level of cross-linking. DMP 504 is very hygroscopic and has a tendency to gain or lose moisture with ease. The transfer of moisture from the capsule shell to DMP 504 powder contained in a hard gelatin capsule can be expected, and if a low water content of the capsule shell is achieved, the capsules become brittle and fracture easily. The sorption isotherm for DMP 504 was generated by storing the drug substance under various relative humidity conditions. After equilibrium, the moisture contents for the samples of individual isotherm points were measured by thermogravimetric analyses. This report applies the sorption-desorption moisture transfer (SDMT) model to predict the equilibrium relative humidity in a system containing DMP 504 in hard gelatin capsules and to establish target loss on drying values for DMP 504 and the capsule shell. Application of this SDMT model resulted in finding a solution to the brittleness problem. The moisture levels of capsule shells and contents for two formulations in a 12-month stability program are also reported here. Results of this study further demonstrate that the SDMT model can be used as a tool to guide the formulator to select optimal initial moisture contents for the empty capsule shell and the formulation to avoid the incidence of brittle capsule problems.
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OBJECTIVES: To determine current geographic distribution of pediatricians in the United States, to assess the changes in the geographic distribution of pediatricians between 1982 and 1992, and to identify factors associated with the distribution of pediatricians among the 50 states. METHODS: A data set was constructed using several published data sources including the American Medical Association Physician Masterfile as the principal source for physician information. The pediatrician-to-child population ratio (PCPR, the number of pediatricians per 100 000 people under 18 years of age) was calculated to compare the distribution of pediatricians among states and the distributional changes between 1982 and 1992. Lorenz curves and Gini indices were used to describe distributions and to compare distributions across time periods. Linear regression analysis was performed to assess the relationship between PCPR (dependent variable) with 9 predictor variables. RESULTS: Between 1982 and 1992, there was a 5.4% increase in the United States (US) child population and a 46.1% increase in the number of pediatricians in patient care. During that time period, the PCPR increased by 38.6% from 35.1 per 100 000 to 48.6 per 100 000. There was a more than 4-fold difference in the PCPRs of the highest state (Maryland, 84.3) and the lowest state (Idaho, 18.5) in 1992. The PCPR increased in all 50 states, but varied from a 4.1% increase in Wyoming to a 63.4% increase in Massachusetts. The Lorenz curve showed that pediatricians were less evenly distributed than all physicians, but more evenly distributed than pediatric cardiologists. Between 1982 to 1992 the Gini index decreased 9.8% for all physicians and 10.2% for pediatric cardiologists, but only 1. 9% for pediatricians. Since a decrease in the Gini index signifies better overall distribution, these changes are relatively modest for pediatricians as a whole, especially when compared to other physicians. Regression analysis showed that a higher PCPR was associated with a greater number of residency positions per 100 000 children and with the per capita income of the state (R = .93). CONCLUSIONS: The distribution of pediatricians does not parallel the distribution of the child population in the US, nor has this distribution changed substantially in spite of a 38.6% increase in the PCPR. Pediatricians tend to concentrate in states with high per capita income and in states with a larger number of residency training positions. The failure of market forces to improve the geographic distribution may require manpower policy changes designed to improve distribution in underrepresented states. The uncertain impact of market changes due to increased use of managed care could affect distributional requirements of pediatricians in the future.
The purpose of this study was to characterize the physicochemical properties of DMP 504 and lay the foundation for formulation development. Thermal properties were characterized by DSC and TGA and moisture sorption and desorption by TGA. The association rate and equilibrium binding capacity of the polymer for a prototype bile acid was evaluated using cholic acid, and solid state stability was examined at 25 degrees C, 40 degrees C (with and without 5% added water), 60 degrees C, and 600 foot candles/25 degrees C. The solid state excipient compatibility of binary mixtures of DMP 504 and several commonly used pharmaceutical excipients was also evaluated. Thermal analysis of the polymer showed a glass transition temperature at approximately 95 degrees C and no melting point, indicating a highly amorphous macromolecular structure with thermal stability up to 250 degrees C. Moisture sorption and desorption isotherms at controlled humidity ranging from 11% to 97% RH did not display hysteresis. Cholic acid associated with DMP 504 extremely rapidly so that binding was essentially complete within 5 min. Scatchard analysis of the equilibrium binding of cholic acid to DMP 504 was unconventional, and indicated that the system was exhibiting positive cooperative behavior. Modeling the binding curve for a system exhibiting cooperative behavior indicated a maximum binding capacity of DMP 504 for cholic acid in phosphate buffered saline (pH 7.0) of 4.9 mumol/mg, and a cooperativity value, P, of 2.2 implying that binding of one molecule promotes the binding of additional molecules. DMP 504, a hygroscopic, amorphous cross-linked polymer with a tendency to gain or lose moisture with ease, is stable in the solid state, either drug substance alone or in presence of excipients, at normal storage temperatures and light, and under controlled conditions of humidity.
This study was designed to assess the effects of isoflurane (ISO) on the electrophysiological properties of the accessory pathway, atrium, ventricle, and AV node in children with the Wolff-Parkinson-White (WPW) syndrome. The results of programmed electrical stimulation were analyzed in 51 patients (4 months to 17 years of age) with WPW. The study population was divided into two groups. Twenty-seven patients received local anesthesia and intramuscular injection of meperidine, promethazine, and chlorpromazine (MPC group). Twenty-four patients received general anesthesia with ISO inhalation (ISO group). We compared the antegrade effective refractory period of the accessory pathway (antegrade APERP), ventricular effective refractory period (VERP), atrial effective refractory period (AERP), AH interval, and cycle length of circus movement tachycardia (CMT-CL) in 12 pairs of age and sex matched patients selected from the MPC and ISO groups. Of the 12 pairs of age and sex matched patients, antegrade APERP in patients who received ISO (299 +/- 17 ms, mean +/- SEM) was significantly longer as compared with matched patients in the MPC group (262 +/- 5 ms, P < 0.025). The VERP and AERP in patients from the ISO group were significantly prolonged compared with the MPC patients (239 +/- 7 vs 210 +/- 8 ms, P < 0.025, and 228 +/- 11 vs 180 +/- 6 ms, P < 0.01, respectively). There was no significant difference in the AH interval or CMT-CL between the two subgroups. Thus, ISO prolongs the antegrade APERPs as well as the effective refractory periods of atrial and ventricular muscle in children with WPW, while the AH interval and CMT-CL appear to be unaffected. Care must be taken in interpreting measurements of the antegrade APERP made in patients under general anesthesia for RF ablation of accessory pathways.
The anterograde effective refractory period of the accessory pathway is age-dependent in pediatric patients with the WPW syndrome. Thus, age should be considered when developing electrophysiologic criteria for the risk of hypotensive arrhythmias in these patients. In addition, general anesthesia must also be considered in interpreting age-related changes in the anterograde APERP, especially in children.
The purpose of this experiment is to use a low-temperature thermoplastic material (Aquaplast) to make a modified custom-molded cervical orthosis. Sixteen normal young subjects who do not have previous cervical problems are tested in this study. This modified orthosis is applied on these volunteers so that external fixation of the cervical spine can be tested. Various roentgenograms for cervical flexion and extension, as well as neutral position and lateral bending, are taken to determine the fixation property of the cervical spine. A study of rotation of the cervical spine is also carried out through goniometer measurements. This clinical study proves that this low-temperature thermoplastic cervical orthosis provides good fixation for the cervical spine, especially in flexion and rotation, but is not suitable for C1- and C2-injured patients.
Tuna are unique among teleost fishes in being thermoconserving. Vascular counter-current heat exchangers maintain body temperatures above ambient water temperature, thereby improving locomotor muscle efficiency, especially at burst speeds and when pursuing prey below the thermocline. Because tuna also occasionally swim rapidly in warm surface waters, it has been hypothesized that tuna thermoregulate to accommodate changing activity levels or ambient temperatures. But previous field experiments have been unable to demonstrate definitively short-latency, mammalian-type physiological thermoregulation. Here we show using telemetered data that free-ranging bigeye tuna (Thunnus obesus) can rapidly alter whole-body thermal conductivity by two orders of magnitude. The heat exchangers are disengaged to allow rapid warming as the tuna ascend from cold water into warmer surface waters, and are reactivated to conserve heat when they return into the depths. Combining physiological and behavioural thermoregulation expands the foraging space of bigeye tuna into otherwise prohibitively cold, deep water.
Laboratory tests are commonly used to aid in monitoring disease activity in patients with systemic lupus erythematosus. Typically, tests for antinative DNA, complement, acute phase reactants, and sometimes circulating immune complexes are used for this purpose. More recently, tests for complement activation products and immunocyte activation have been suggested. We measured antinative DNA, C4, Westergren sedimentation rate, iC3b, Bb, and sIL-2R levels in a group of 100 patients with SLE evaluated clinically for activity by a modified version of the Systemic Lupus Activity Measure (SLAM); iC3b and Bb were studied in 71 of the patients and sIL-2R in 52. We found that sIL-2R and sedimentation rate correlated best with SLAM, anti-DNA was intermediate, and C4, iC3b, and Bb correlated the least. None of the tests predicted severity of disease, but sIL-2R was highest in patients with active renal disease.
This study examined the changes from the initial peak flows and oxygen saturations (OSAT) of wheezing children at presentation to the emergency department through their treatment in the emergency department. Data was collected prospectively on 785 patients 5 to 20 years of age during an 11-month period from November 1, 1990, to September 30, 1991. Both the initial OSAT and peak flows were correlated with the number of bronchodilator treatments required in the emergency department and with the need for hospitalization. Both the initial OSAT and the peak flows had a limited ability to predict the need for hospitalization. Oxygen saturation appears to be a valid measure of wheezing severity and is more easily obtained in children of all ages. Following bronchodilator treatment, peak flow results in a larger quantitative improvement than OSAT; however, this difference does not appear to have any significant advantage. Aerosolized albuterol and subcutaneous epinephrine resulted in a similar degree of improvement as measured by peak flow and by oxygen saturation, with clinically similar changes in heart rate.
Seventy-one patients with systemic lupus erythematosus (SLE), seen in an outpatient setting for follow-up evaluation during a 3-mo period, were tested (in addition to routine lupus monitoring studies) with enzyme immunoassays (EIAs) for anti-DNA, iC3b, and factor Bb to determine the relationship of these test results to disease activity. SLE activity was scored by four previously reported scoring systems, and six patients were identified as active by all four systems. We found that the EIA for anti-DNA was the best indicator of disease activity and that iC3b and Bb were not informative for this purpose in this group of patients. Mean iC3b levels were higher in a subset of seven patients with past biopsy evidence of severe (WHO class IV) glomerulonephritis than in the rest of the study population, even though none of these patients had active disease at the time of this study.
Positive predictive values for the diagnosis of systemic lupus erythematosus (SLE) were determined for two antinative DNA assays: a Farr-type radioimmunoassay (RIA) and a solid-phase enzyme immunoassay (EIA). The study population consisted of all patients whose EIA anti-DNA results were positive (greater than 250 IU) during a 150 day period; in addition all patients whose EIA anti-DNA results were 100-250 IU during the first 25 days of this period were also included. Simultaneous Farr RIA were performed on all sera, and the Crithidia luciliae immunofluorescent assay was also carried out on those with positive RIA and/or EIA results. Diagnoses were established by chart review, and disease activity was scored for SLE patients. Positive predictive values for SLE were dependent on the level of test positivity, and "normal" limits of 10% binding for the Farr RIA and 800 IU for the EIA gave comparable results. Combination with Crithidia luciliae immunofluorescence increased the sensitivity of both assays, especially the EIA. Results of both assays correlated significantly with activity scores in SLE patients.
The general technologies for fabricating drug delivery systems are briefly discussed in the present review. Furthermore, two types of commonly used polymers, biodegradable aliphatic polyesters for parenteral administration and cellulose-based polymers for oral uses, are presented by means of selected examples of their properties and applications to control drug release.
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The authors have developed an objective method for quantitation of herpes simplex virus in the corneal epithelium of rabbits. At appropriate times postinfection, full-thickness rabbit corneas were removed by trephination and subjected to one cycle of freezing and thawing. The corneal epithelium was then disrupted by sonication. The amount of infectious virus recovered from sonicated specimens was determined by an in vitro plaque assay, providing a measure of the quantity of virus present during the acute stage of herpetic keratitis. Using this technique, the authors found that the mean virus titer was reduced from 1.5 X 10(5) plaque forming units (pfu) per cornea in control rabbits to less than 200 pfu per cornea in rabbits treated topically for 2 days with 1% trifluridine. In contrast, instillation of 1% prednisolone acetate resulted in the persistence of higher levels of virus (275 pfu) than those observed in control rabbits (3 pfu) 4 days after the cessation of therapy.
Gel Tears, a clear, semisolid formulation of synthetic, high molecular weight, cross-linked polymers of acrylic acid, persists in the conjunctival sac for hours after topical instillation, slowly melting while absorbing fluid and retaining it locally. In the present study of 55 patients (106 eyes) with severe dry eyes, who were unable to obtain ocular comfort with frequent administration of a wide variety of commercially available artificial tear preparations, 78% were improved by Gel Tear therapy. Subjective symptoms such as burning, stinging, foreign body sensation, dryness, and photophobia were significantly (P less than 0.001) alleviated, while objective signs concurrently improved but to a lesser degree. No patient required Gel Tears more often than four times daily. Most maintained optimal comfort on a dose of twice daily or less, and several patients previously unable to obtain ocular comfort with hourly administered conventional artificial tears required Gel Tears less than once a day.
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