Search PubMed⌕ Search

Biomedical subjects

J C Chan

Publications and source records attributed to J C Chan.

At least 289 records · Page 16Linked to original sources
PubMed1990

Masking procedure, randomization and stratification, and compliance monitoring in the Growth Failure in Children with Renal Diseases Study.

Ensuring the integrity of a study such as the GFRD Study requires close cooperation among all groups involved with the study and the patient. Many factors may influence the outcome and validity of a multicenter, double-masked, randomized trial. Any dosage modifications that may need to be made rely totally on established communication between the centers, the DCC, and the Core Pharmacy. When the procedures outlined above are followed, masking is ensured and patient compliance can be measured.

Calcitriol↗
PubMed1990

Descriptions of the participating centers and patient population in the Growth Failure in Children with Renal Diseases Study.

The Growth Failure in Children With Renal Diseases Study, a double-blind, multicenter clinical trial with 108 children entered into the control period over 4.3 years of patient enrollment (December 1984 to April 1989), is being extended for 3 years (December 1988 to December 1991) to provide the time needed to accrue additional patients, aged between 1 1/2 and 10 years, with glomerular filtration rates of 20 to 75 ml/min/1.73 m2. The study design of randomization to two treatment arms (1,25-dihydroxyvitamin D vs dihydrotachysterol) requires a total of 108 patients with a minimum of 6 months of treatment to test the long-term effectiveness and safety of 1,25-dihydroxyvitamin D, an essential part of the therapeutic regimen for children with chronic renal insufficiency. The frequent longitudinal assessments of nutrition and growth in children with chronic renal insufficiency can better define the natural history of renal disease and its influence on growth. Similar data in the treatment period will define the impact of treatment with 1,25-dihydroxyvitamin D3 versus dihydrotachysterol on this natural history. Linear growth must be observed long enough (6 to 12 months minimum) to permit valid quantitation and comparison of the two vitamin D treatment arms, the multiple confounding variables that affect growth (e.g., steroid therapy, diabetes mellitus, prior vitamin D treatment) must be rigorously excluded or controlled, and the assignment of patients to the two groups must be random. These controls--sufficient study duration, sufficient patient numbers, and randomization--should eliminate extraneous sources of variation, including seasonal periodicity. This carefully developed, double-blind clinical trial with multiple participating centers and an effective organizational structure is coming close to achieving the goals of the study. An explosion of data regarding the natural history of chronic renal insufficiency and its treatment with vitamin D metabolites will be forthcoming at the conclusion of the study.

Child↗
PubMed1990

Data coordination and management in the Growth Failure in Children with Renal Diseases Study.

The DDC of the GFRD Study works closely with the Administrative Core and with all participating clinical centers to ensure the timely collection of accurate, reliable, and complete data. The development and maintenance of a data-base management system, including continuous monitoring of all data, represent primary responsibilities of the DCC. Coordination and communication tasks in the multicenter study have been challenging but rewarding. Proper planning and positive attitudes have enhanced the effectiveness of the DCC throughout this clinical trial.

Anthropometry↗
PubMed1990

Linear growth and anthropometric and nutritional measurements in children with mild to moderate renal insufficiency: a report of the Growth Failure in Children with Renal Diseases Study.

During the control period of the Growth Failure in Children With Renal Diseases Study, investigators at 23 centers were able to observe and characterize growth and to make anthropometric and nutritional measurements in 82 children with mild to moderate renal insufficiency. As a multicenter, controlled clinical trial designed to study the relative efficacy of 1,25-dihydroxyvitamin D3 and dihydrotachysterol in the treatment of renal osteodystrophy, no prior vitamin D exposure and a creatinine clearance of 25 to 75 ml/min/1.73 m2 were criteria for entrance into the clinical trial. Ages ranged from 18 months to 11 years (mean 5.6 +/- 3.1 years), and distribution by age category was as follows: 38%, 1 to 3 years; 28%, 4 to 6 years; and 34%, 7 to 10 years. There was a 3:1 male/female ratio; 72% of the patients had congenital disease by the International Classification of Diseases (ninth revision). Mean creatinine clearance was 49.5 +/- 20 ml/min/1.73 m2. The C-terminal parathyroid hormone values (1121 +/- 1562 pg/ml) were well above 2 SD of the mean of a normal growing population of similar age. Parathyroid hormone values correlated with degree of renal insufficiency (r = -0.57) and with height by bone age but not with chronologic height or growth velocity. The bone age/height age ratio, a predictor of growth potential in normal children, was low for the entire series of patients (0.88 +/- 0.35) but failed to correlate with growth velocity and was negatively correlated with rising parathyroid hormone levels. Average values for height, weight, triceps skin fold, mid-arm muscle circumference, and body mass index were within 2 SD of the mean of the normal population, although measurements for the 1- to 3-year age group were significantly less than those of the older patients. Total energy intake averaged less than 86% of the recommended dietary allowances; total protein intake was more than 161% of the allowance. Nitrogen balance in 23 patients was positive and correlated most significantly with increasing energy intake (r = 0.6). Growth velocity, calculated from the interval gain during the month control period, averaged +0.3 SD, with the highest growth velocity z scores recorded for those with acquired disease. A growth velocity index, expressed as the slope of the regression between change in height SD and growth velocity z score, was used to describe the growth accomplished in the control period by age category.(ABSTRACT TRUNCATED AT 400 WORDS)

Age Determination by Skeleton↗
PubMed1990

Serum osteocalcin concentrations in children with chronic renal insufficiency who are not undergoing dialysis. Growth Failure in Children with Renal Diseases Study.

This report describes the serum osteocalcin values in children with mild to moderate, but relatively stable, renal dysfunction followed in the Growth Failure in Children With Renal Diseases Study. This report is derived from data obtained during the control period (6 months) before the initiation of vitamin D therapy. Up to three measurements per patient were obtained. Serum osteocalcin concentration was compared with creatinine clearance (glomerular filtration rate) calculated by the Schwartz formula; with serum concentrations of alkaline phosphatase, parathyroid hormone, and bicarbonate; and with the percentages of the recommended dietary allowances of calories and protein ingested. By standard correlation techniques, there appeared to be an inverse correlation between calculated creatinine clearance and serum osteocalcin concentration, and a direct correlation between serum osteocalcin and parathyroid hormone values. However, when we employed a statistical technique that takes into account repeated measures in the same patient, no correlation was found between calculated glomerular filtration rate and serum osteocalcin concentration, and no direct correlation was found between serum osteocalcin and parathyroid hormone values. The lack of a correlation between calculated glomerular filtration rate and serum osteocalcin values may be due to large fluctuations in the serum osteocalcin concentration, even though renal function is relatively stable.

Alkaline Phosphatase↗
PubMed1990

Serum soluble interleukin 2 receptor in hyperthyroid Graves' disease and effect of carbimazole therapy.

To study the activation of T lymphocytes in hyperthyroid Graves' disease, the serum concentrations of soluble interleukin 2 receptors (sIL2R) were determined during active thyrotoxicosis and following the return to a euthyroid state with carbimazole therapy. Serum sIL2R was measured by an enzyme linked immunoassay. The mean +/- SD serum sIL2R concentration during untreated hyperthyroidism was elevated as compared with controls (919.1 +/- 523.4 vs 374.2 +/- 189.4 U/ml, P less than 0.005). However, after carbimazole therapy the serum sIL2R in euthyroid patients fell to 377.9 +/- 90.3 U/ml, which did not differ from healthy controls. Serum sIL2R correlated significantly with the serum free T3 only during hyperthyroidism (r = 0.678, P less than 0.01). Our study suggests that in vivo measurement of serum sIL2R released from activated T lymphocytes is a useful immunological indicator of disease activity.

Adult↗
PubMed1990

Estimation of eardrum acoustic pressure and of ear canal length from remote points in the canal.

Sound pressure distributions in the human ear canal, whether unoccluded or occluded with ear molds, were studied using a probe tube technique. On average, for frequencies below 6 kHz, the measuring probe tube had to be placed within 8 mm of the vertical plane containing the top of the eardrum (TOD), determined optically, in order to obtain sound pressure magnitudes within 6 dB of "eardrum pressure." To obtain that accuracy in all of the eight subjects studied, the probe had to be within 6 mm of the TOD. Since probe location relative to the drum has to be known, a purely acoustic method was developed which can be conveniently used to localize the probe-tip position, utilizing the standing wave property of the sound pressure in the ear canal. The acoustically estimated "drum location" generally lay between the optically determined vertical planes containing the TOD and the umbo. On average, the "drum location" fell 1 mm medial to the TOD. Of the 32 estimates made acoustically in various occluded and unoccluded conditions in 14 subjects, 30 estimates lay within a +/- 2-mm range of this average.

Acoustic Stimulation↗
PubMed1990

Direction-dependent spectral properties of cat external ear: new data and cross-species comparisons.

Free-field to eardrum transfer functions were measured in anesthetized cats inside an anechoic chamber. Direction-dependent transformations were determined by measurement of sound-pressure levels using a small probe tube microphone surgically implanted in a ventral position near the tympanic membrane. Loudspeaker and probe microphone characteristics were eliminated by subtraction of the signal recorded in the free field with no animal present. Complexities of the transfer function, which include the presence of prominent spectral notches in the 8- to 18-kHz frequency region, are due primarily to the acoustical properties of the pinna. Differential amplification of frequency components within the broadband stimulus occurs as a function of source direction. Spectral features vary systematically with changes in both elevation (EL) and azimuth (AZ). The contrast between a notch and its shoulders is enhanced in the interaural spectral records. Spectral data from single source locations and spatial data for single frequencies at many locations are presented and comparisons with other species are drawn. It is suggested that spectral features in the 8- to 18-kHz region provide some of the necessary spectral information for sound localization and that the contrast in spectral energy between the frequencies at the notch and its shoulders is a potential directional cue.

Acoustic Stimulation↗
PubMed1990

Interaural time sensitivity in medial superior olive of cat.

1. We studied the sensitivity of cells in the medial superior olive (MSO) of the anesthetized cat to variations in interaural phase differences (IPDs) of low-frequency tones and in interaural time differences (ITDs) of tones and broad-band noise signals. Our sample consisted of 39 cells histologically localized to the MSO. 2. All but one of the cells had characteristic frequencies less than 3 kHz, and 79% were sensitive to ITDs and IPDs. More than one-half (56%) of the cells responded to monaural stimulation of either ear, and both the binaural and monaural responses were highly phase locked. All of the cells that were sensitive to IPDs and monaurally driven by either ear responded in accord with that predicted by the coincidence model of Jeffress, as judged by comparisons of the phases at which the monaural and binaural responses occurred. The optimal IPDs were tightly clustered between 0.0 and 0.2 cycles. Most cells exhibited facilitation of the response at favorable ITDs and inhibition at unfavorable ITDs compared with the monaural responses. 3. Cells in the MSO exhibited characteristic delay, as judged by a linear relationship between the mean interaural phase and stimulating frequency. Characteristic phases were clustered near 0 indicating the most cells responded maximally when the two input tones were in phase. With the use of the binaural beat stimulus we found no differential selectivity for either the direction or speed of interaural phase changes. 4. The cells were also sensitive to ITDs of broad-band noise signals. The ITD curve in response to broad-band noise was similar to that predicted by the composite curve, which was calculated by linearly summating the tonal responses over the frequencies in the response area of the cell. Most (93%) of the peaks of the composite curves were between 0 and +400 microseconds, corresponding to locations in the contralateral sound field. Moreover, computer cross correlations of the monaural spike trains were similar to the ITD curve generated binaurally for both correlated and uncorrelated noise signals to the two ears. Thus our data suggest that the cells in the MSO behave much like cross-correlators. 5. By combining data from different animals and lcoating each cell on a standard MSO, we found evidence for a spatial map of ITDs across the anterior-posterior (A-P) axis of the MSO.(ABSTRACT TRUNCATED AT 400 WORDS)

Acoustic Stimulation↗
PubMed1990

Attenuation of tumor necrosis factor-induced endothelial cell cytotoxicity and neutrophil chemiluminescence.

Our laboratory has previously shown that the administration of tumor necrosis factor (TNF), a cytokine produced by activated mononuclear cells, to guinea pigs produces a syndrome similar to gram-negative sepsis or ARDS. Pentoxifylline (PTX), a methylxanthine, protects against TNF-induced and sepsis-induced acute lung injury in vivo. We now report on in vitro cellular studies of PMN-mediated cellular injury and its attenuation. We studied TNF-induced bovine pulmonary artery endothelial cell (EC) cytotoxicity both with and without PMN. A 51Cr release assay was used to measure EC damage. Further, we investigated PMN function in response to TNF by measuring chemiluminescence. Agents that attenuate EC damage and PMN activation were evaluated in the above assays. Results revealed that TNF causes EC injury (p less than 0.05) and PMN increase TNF-induced EC injury. Furthermore, PTX, aminophylline (AMPH), caffeine, and forskolin attenuate TNF-induced EC cytotoxicity only in the presence of PMN (p less than 0.05). Of interest, dibutyryl cAMP (DBcAMP) protects EC from TNF-induced injury both with and without PMN. Agents that may increase cAMP levels in PMN (PTX, DBcAMP, forskolin, isobutyl methylxanthine, and terbutaline) significantly attenuate TNF-induced PMN chemiluminescence (p less than 0.05). We conclude that TNF causes EC damage and PMN increase this damage. Furthermore, PTX, AMPH, caffeine, and forskolin can attenuate TNF-induced EC injury in the presence of PMN, whereas DBcAMP attenuates TNF-induced EC injury with and without PMN. In addition, agents that may increase intracellular cAMP levels in PMN can attenuate TNF-induced PMN chemiluminescence. Thus, these agents likely attenuate TNF-induced PMN-mediated EC injury through their inhibitory effects on PMN.

Aminophylline↗