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Biomedical subjects

W Tong

Publications and source records attributed to W Tong.

At least 19 recordsLinked to original sources
PubMed1992

Use of adaptive control with feedback to individualize suramin dosing.

Suramin is the first putative growth factor inhibitor in clinical trial that has demonstrated antitumor activity. Administration of suramin is complicated by a narrow therapeutic index and significant interpatient variability of measured pharmacokinetic parameters. Because both antitumor response and dose-limiting toxicities are related to plasma suramin concentration profiles, individualized dose schedules are required for optimal administration of the compound. In this report, the use of optimal sampling theory to derive sparse data monitoring and control strategies for use with suramin is described. A fixed rate continuous infusion schedule was used in seven patients, and the time to peak concentration (280-300 micrograms/ml) ranged from 7.7-21 days (mean, 13.2 days) with a decline to 150 micrograms/ml in 3-22 days (mean, 11 days). An initial population pharmacokinetic model was fit using a maximum likelihood algorithm. The mean volume of the central compartment was 4.5 +/- 6.7 liters/m2, volume of the peripheral compartment 10.6 +/- 1.4 liters/m2, distributional half-life 25 +/- 5.4 h, and elimination half-life 29.7 +/- 6.9 h. The terminal half-life was shorter than previously reported. These parameters were used as the initial population model for an iterative 2-stage analysis. The resulting distributional half-life of 22.3 +/- 2.7 h and elimination half-life of 28.2 +/- 5.0 h were similar, reflecting the intensive sampling. The iterative 2-stage analysis model was then used to determine the optimal sampling times and to simulate 20 data sets for a protocol designed to maintain plasma concentrations in a defined concentration range. This strategy is currently under investigation in phase I clinical trials.

Adenocarcinoma↗
PubMed1992

[A study on the regulation of ACTH secretion in rat pituitary cells].

In addition to method of ACTH RIA, a rat pituitary cell perfusion system was developed for the assessment of pituitary cells in stimulating and inhibiting ACTH secretion induced by some substances. Hypothalamic extract stimulated the ACTH secretion in a dose-dependent manner. AVP, cAMP, Ca2+, K+, noradrenaline, metoclopramide and haloperidol also had some stimulating effect. Dexamethasone and dopamine inhibited the basal ACTH secretion of pituitary cell and antagonized the effect of the various stimulating substances. Cyproheptadine could antagonize the effect of some of the stimulating substances while GABA had no marked inhibiting effect.

Adrenocorticotropic Hormone↗
PubMed1990

Landmarking of cephalograms using a microcomputer system.

Landmarks, or certain characteristic reference points, on cephalograms are used as a diagnostic aid employed in treatment planning by orthodontists. This work presents an algorithm for recognizing some anatomical features and locating landmarks on lateral skull X rays (cephalograms) using digital image processing and feature recognition techniques. A cephalogram is digitized and stored in a computer memory. Prefiltering is applied to remove image noise. The bony and flesh profiles of jaw and front face are traced. Using these profiles the algorithm locates 17 points on the image, some on bony features and others on soft tissue. To locate these points, edge-enhancement, thresholding, and edge-detection techniques are applied. The algorithm can be run on an IBM compatible microcomputer.

Algorithms↗
PubMed1990

Wear of composite resin in vitro: a testing machine with rubber plate. Preliminary results.

A new machine was developed to study the wear of dental filling materials in vitro. Four products: amalgam, Adaptic, Clearfil and acrylic resin were tested. Wear was measured quantitatively by weighing the specimen, and the wear pattern was studied qualitatively with a scanning electron microscope (SEM). A comparison was made with materials that were placed in the mouth for a prolonged period. It was found that the in vitro wear pattern was comparable to that found in vivo.

Acrylic Resins↗
PubMed1989

A study of surfaces developed on composite resins in vivo during 4.5 years; observations by SEM.

In this study seven commercial composite resins, one experimental composite and one dental amalgam were investigated. These materials were inserted into the cavities of denture molar teeth in different patients. After clinical service for 3, 9, 12, 24 and 54 months the specimens were removed and observed by scanning electron microscopy. The wear patterns of the filling materials and their changes with continuing clinical service for 4.5 years suggest that the abrasive mechanism of conventional composite resin is as follows. The softer resin matrix is worn away and inorganic filler particles are exposed, thereafter they loosen and fall off. As this process proceeds the composite resin is worn away. This process continues with time. In the case of microfilled composite, the organic fillers and resin matrix are worn away at the same rate. After long-term clinical service some cracks could be seen on the wear surface between the organic filler agglomerates and the resin matrix.

Chemical Phenomena↗
PubMed1988

Phase I trial and clinical pharmacological evaluation of hexamethylene bisacetamide administration by ten-day continuous intravenous infusion at twenty-eight-day intervals.

We have treated 33 patients with different types of advanced cancer by 10-day continuous i.v. infusion courses of hexamethylene bisacetamide (HMBA), a drug that produces differentiation of a variety of transformed cell lines on prolonged exposure in vitro to drug concentrations of 3 to 5 mM. In this dose-finding and pharmacokinetic study, five dosage levels were explored from 12 to 28 g/m2/day. Patients who had not shown progression of disease were given repeat courses of therapy at 28-day intervals. Seventy-two courses of therapy were administered; 17 patients received one course; eight patients received two; six patients received three; and one patient each received four and 17+ courses, respectively. The maximal tolerated dose was 28 g/m2/day for 10 days; the dose-limiting toxic effects were thrombocytopenia with hemorrhage and central nervous system dysfunction manifesting as disorientation and confusion. Based on these studies the recommended dosage for Phase II studies by the 10-day schedule is 24 g/m2/day. Pharmacokinetic studies demonstrated rapid clearance of HMBA from plasma; the decay phase data fit a one compartment model with a mean plasma half-life of 2.5 h and a range from 0.6 to 5.8 h. Mean plasma steady-state levels in our patients were 0.37, 0.58, 0.86, 0.88, and 1.42 mM, at the 12-, 16-, 20-, 24-, and 28-g/m2/day dosage levels, respectively. The data indicate that plasma HMBA concentrations of 1 mM can be maintained for 10 days with acceptable patient tolerance, but that HMBA concentrations in excess of 1.4 mM for 10 days are associated with substantial hematological and central nervous system toxicity. Objective antitumor effects were observed in five patients; one woman with non-small cell lung cancer, who has received 17+ courses over a period of 28+ mo, achieved a partial remission that continues at 28+ mo on therapy. Transient regression of cutaneous metastases was observed in three patients with breast carcinoma and one patient with colorectal carcinoma.

Acetamides↗
PubMed1988

Phase I clinical and pharmacokinetic study of trimetrexate using a daily x5 schedule.

Trimetrexate (TMQ; NSC 352122) is a potent inhibitor of dihydrofolate reductase with good activity against murine i.p.-implanted B16 melanoma and colon 26 tumors. Preclinical antineoplastic activity, demonstrated schedule dependency, and data suggesting effectiveness against methotrexate-resistant cells prompted a Phase I clinical and pharmacokinetic study of trimetrexate using an i.v. daily x5 schedule. Forty-three good performance status patients were treated with 12 dose levels using daily doses varying from 0.5 to 15 mg/m2/d. Plasma and urine samples were obtained for pharmacokinetic analysis using a high-performance liquid chromatographic method. Myelosuppression was dose limiting and 15 mg/m2/d x5 was the maximum tolerated dose. White blood cell (WBC) and platelet toxicity were noted at doses of 1.6 mg/m2 and above. Median WBC and platelet nadirs occurred on approximately Days 11-12 with recovery by Days 15-18. Nonhematological toxicity included mucositis, nausea and vomiting, stomatitis, diarrhea, and rash. Evidence for antitumor activity was seen in seven patients. Trimetrexate elimination from plasma could be represented as either a bi- or triexponential process. Terminal elimination half-lives were in the range of 5-14 h in patients represented by a triexponential model. Approximately 10-20% of the dose administered was excreted in urine over a 24-h period. The recommended starting dose for patients in Phase II trials using the d x5 i.v. schedule is 8.0 mg/m2/d repeated every 21 days. Dose escalations may be possible depending on the extent of prior therapy and individual tolerance of the drug.

Adolescent↗
PubMed1985

Wear patterns of composite restorative resins in vivo; observations by scanning electron microscopy.

In this study, the wear pattern of seven commercial composite resins, one experimental composite and one dental amalgam were investigated. These materials were separately inserted in a separation preparation cavity of the patient's mouth. After clinical service for 3, 9 and 12 months the specimens were taken out and observed by scanning electron microscopy (SEM). It was found that the softer resin matrix wore away first while the inorganic filler particles showed no signs of abrasive wear, whereafter filler particles were loosened once there was no support of the resin matrix around them.

Composite Resins↗
PubMed1976

Stimulatory actions of thyrotropin and dibutyryl cyclic AMP on transcription and translation in the regulation of thyroidal protein synthesis.

When beef thyroid cells were incubated with thyrotropin and then tested for protein synthesizing activity, the stimulatory effect of thyrotropin appeared in two distinct phases: first, an immediate stimulation which continued as long as thyrotropin was present, but died away promptly after withdrawal of the added thyrotropin; and second, a delayed stimulation with a lag period of 1 to 2 h, which persisted after thyrotropin withdrawal. The fast and the delayed effects each stimulated protein synthesis by about 25%, so that after 4 h of thyrotropin treatment, total stimulation amounted to 50% above basal levels of activity. The fast thyrotropin effect was not affected by actinomycin D or cordycepin, and hence is evidently not dependent upon induced RNA synthesis. In contrast, the delayed thyrotropin effect was completely prevented by actinomycin D or cordycepin. These findings suggest that the fast effect of thyrotropin occurs at the translational level to provide for acute adjustments in thyroglobulin production by regulating the rate of translation of existing mRNA. The delayed thyrotropin effect, by initiating certain transcriptional reactions could be the means for selectively inducing the production of specific enzymes or proteins. Both the fast and delayed effects of thyrotropin were faithfully reproduced by dibutyryl cyclic AMP. This finding seems to be the first in vitro demonstration of a cyclic AMP induced transcriptional response to a hormone in mammalian cells.

Animals↗
PubMed1975

Thyroidal autoregulation. Iodide-induced suppression of thyrotropin-stimulated cyclic AMP production and iodinating activity in thyroid cells.

In continuing our study of the thyroidal autoregulation phenomenon, we have investigated the effects of iodide on several thyroidal responses to thyrotropin. Thus, we have found that the 2--4-fold thyrotropin stimulation of protein iodination in beef thyroid cells was reduced about 30% by 4 h of preincubation with 10 muM iodide, and virtually abolished with 50 muM iodide. Similarly the 8-fold thyrotropin stimulation of cyclic AMP accumulation in the cells was reduced about 30% by 3 h of preincubation with 50 muM iodide. It appears therefore that the so-called autoregulation of the thyroid gland does include influences of iodide on the thyrotropin stimulation of cyclic AMP production, iodide transport, and protein iodination which can be demonstrated in vitro in the dispersed thyroid cell system. Two other effects of thyrotropin, namely, the stimulation of [14C]leucine incorporation into protein and of iodide efflux were not at all affected by treatment with excess iodide, and hence may not be subject to the autoregulatory influence of iodide.

Animals↗