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Biomedical subjects

R Yuan

Publications and source records attributed to R Yuan.

At least 37 records · Page 2Linked to original sources
PubMed2000

Urethral obstruction and bilateral ureteral hydronephroses secondary to fecal impaction.

We present a case report of the first adult woman reported to suffer from both urethral obstruction and bilateral ureteral hydronephroses secondary to fecal impaction. The work-up suggested that hypothyroidism might be the cause for fecal impaction. Urinary tract obstruction caused by hypothyroidism-induced fecal impaction has never been reported. Fecal impaction should be considered as one of the causes for urinary tract obstruction.

Aged↗
PubMed2000

Effect of chronic renal failure on the disposition of highly hepatically metabolized drugs.

OBJECTIVE: The objective of this study was to investigate the effect of renal impairment on the disposition of an extensively metabolized drug, i.e., drug X. Drug X has a hepatic extraction ratio of less than 0.1 and free fraction in plasma of less than 1% in healthy volunteers. METHODS: Pharmacokinetic (PK) parameters of drug X were obtained from subjects with normal renal function (I, n = 6), as well as in subjects with mild (II, n = 5), moderate (III, n = 7) and severe renal impairment (IV, n = 5). Disease-PK models were developed to describe the changes of PK parameters with respect to renal function measured by creatinine clearance. While experimentally observed data are presented for drug X, additional simulations were performed for other drugs that are extensively metabolized (extensive metabolism is defined as metabolism that accounts for more than 90% of total drug elimination). The simulated scenarios included drugs that have a low extraction ratio (ER) and with high plasma protein binding (PPB), low ER and with low PPB, high ER and with high PPB, or high ER and with low PPB. RESULTS: Systemic clearance of drug X, a low ER and high PPB drug, in renal patients depended on the simultaneous effects of renal disease on protein binding and intrinsic metabolic clearance. Protein binding of drug X was related to creatinine clearance in an inverse hyperbolic relationship, while the unbound intrinsic metabolic clearance declined linearly with creatinine clearance. Because the disease effects on these two factors offset each other in terms of total systemic clearance, the lowest total systemic clearance was not observed in the severely renal impairment patients, but rather in the moderately impaired group. Additional simulations showed that for low ER drugs that are highly metabolized, the pattern and magnitude of systemic clearance change in renal patients depended on how the disease affected PPB and/or intrinsic metabolic clearance. But the systemic clearance of high ER drugs would not be as susceptible to the effect of renal disease as that of low ER drug. CONCLUSIONS: Chronic renal disease should not be considered as an isolated event that affects only renally excreted drugs. Uremia may also modify the disposition of a highly metabolized drug by changes in plasma protein binding and/or hepatic metabolism.

Area Under Curve↗
PubMed2000

[Reconstruction of the mandible and soft tissue defects with the osteomyocutaneous free fibula flap].

OBJECTIVE: In order to ascertain a material that is ideal both for reconstruction of the composite mandibular defects and for osseointegrated implantation. METHODS: Fifteen osteomyocutaneous fibula flaps were transferred for reconstruction of the mandible and surrounding soft tissues. The characters of the blood supply of the flap, the operation course, the relation of the fibula and dental implants were observed. RESULTS: The osteomyocutaneous fibula flap was supplied by double vessels. The blood supply was reliable even after the fibula was cut into several segments. Periosteal circulation was its main blood supply. The postoperative contour and function of the mandibular region were good. The flap also favours dental implants and denture. CONCLUSION: The osteomyocutaneous fibula flap was the ideal material to reconstruct the defects of mandible and surrounding soft tissues.

Adult↗
PubMed2000

[Expression of platelet derived growth factor receptor-beta in fibroblasts of keloid].

OBJECTIVE: To investigate the expression and distribution of platelet derived growth factor receptor-beta(PDGFR-beta) in normal skin and keloid and to discuss its biological function in keloid formation. METHODS: 1. To detect the expression and distribution of PDGFR-beta in normal skin and keloid tissue by immunohistochemistry; 2. To detect the receptor expression in vitro by Flow cytometry (FCM); 3. To detect the subcellular distribution of receptor by Laser confocal microscope. RESULTS: 1. Immunohistochemistry showed that normal skin and keloid tissue were almost the same in expression but different in distribution of PDGFR-beta; 2. There was more expression of PDGFR-beta in normal fibroblasts than that in keloid fibroblasts in vitro by FCM; 3. Laser confocal microscope revealed that the PDGFR-beta concentrated on the surface of cell membrane in keloid fibroblasts, but in normal skin fibroblasts, the receptors were coagulated on the nuclear membrane and intranucleus. CONCLUSION: Compared with the fibroblasts in vivo, there was a difference of the PDGFR-beta expression in fibroblasts in vitro, more expression of PDGFR-beta in normal fibroblast than that in keloid fibroblast in vitro; and the subcellular distribution of PDGFR-beta was different in normal skin and keloid fibroblasts. The characteristics of the expression and distribution of PDGFR-beta in keloid may contribute to the formation of keloid.

Cells, Cultured↗
PubMed2000

[Laryngostroboscopy in the monitoring of precancerous lesion of vocal cord and in canceration tracing].

OBJECTIVE: To evaluate the value of laryngostroboscopy in the monitoring of precancerous lesion of vocal cord and in the canceration tracing. METHODS: Fifty-two cases of precancerous lesion of vocal cord were examined under Laryngostroboscope. The modifications of mucosal wave and amplitude of vocal cord vibration were observed. All cases were monitored for 1-6 years. RESULTS: The mucosal wave was weak in 45 of 52 cases (86.3%) and the amplitude of vocal cord vibration was weak in 4 of 52 cases (9.6%) with precancerous lesions. However, the mucosal wave disappeared and the amplitude of vocal cord vibration weakened in all 14 cases with early glottic cancer. CONCLUSION: Laryngostroboscopy can be used in diagnosis of glottic precancerous lesion and distinguishing it from the early glottic cancer. It is also an effective means of canceration tracing.

Carcinoma, Squamous Cell↗
PubMed1999

Coordinate alterations in the expression of BRCA1, BRCA2, p300, and Rad51 in response to genotoxic and other stresses in human prostate cancer cells.

BACKGROUND: BRCA1 and BRCA2 participate in cell cycle progression, apoptosis, and DNA repair pathways. The latter role may be mediated by interaction with DNA recombinase Rad51. The purpose of this study was to evaluate the effects of genotoxic and other cytotoxic agents on expression of DNA damage-response genes (BRCA1, BRCA2, p300, and Rad51) in human prostate cancer cells. METHODS: Subconfluent proliferating cultures of Tsu-Prl or DU-145 cells were treated with various stressful agents and assayed 24 hr later for alterations in: 1) mRNA expression (by semiquantitative reverse transcription-PCR); 2) cell viability (by trypan blue dye exclusion); and 3) protein expression (by Western blotting). RESULTS: Of 26 agents screened, BRCA1 and BRCA2 mRNA reductions were observed in both cell lines after exposure to adriamycin (ADR), camptothecin (CPT), sodium selenite (SLN), and ultraviolet radiation (UV), while nitrogen mustard (HN2) caused mRNA reduction in DU-145 but not in Tsu-Prl. Inhibition of BRCA1/2 expression by ADR and HN2 was blocked by cycloheximide, suggesting that this requires new protein synthesis, while inhibition by CPT, SLN, and UV did not require protein synthesis. Reduction of p300 and Rad51 mRNA levels occurred in parallel with that of BRCA1/2, suggesting coordinate regulation of these genes. The ability of an agent to inhibit mRNA expression was not directly correlated with cytotoxicity. ADR, CPT, UV, and SLN also caused reduction of protein levels; but the kinetics of decreases in protein vs. mRNA differed. After ADR treatment, high molecular weight (Mr hyperphosphorylated) BRCA1 decreased more rapidly than the low Mr species. BRCA2 showed a more rapid decrease in protein than mRNA, while Rad51 showed the opposite. By 48 and 72 hr post-ADR, all four mRNAs and proteins were reduced to well below control levels, except for Rad51 protein, which was only moderately decreased. CONCLUSIONS: Selected DNA-damaging agents (ADR, CPT, and UV) and a reducing agent (SLN) inhibited BRCA1/2, p300, and Rad51 expression in prostate cancer cells, although decreases in mRNA vs. protein did not coincide. We postulate that temporal changes in relative protein levels affect different phases of the stress response, and that the ultimate downregulation of all four genes promotes prostate cancer survival.

BRCA2 Protein↗
PubMed1999

BRCA1 inhibition of estrogen receptor signaling in transfected cells.

Mutations of the breast cancer susceptibility gene BRCA1 confer increased risk for breast, ovarian, and prostatic cancers, but it is not clear why the mutations are associated with these particular tumor types. In transient transfection assays, BRCA1 was found to inhibit signaling by the ligand-activated estrogen receptor (ER-alpha) through the estrogen-responsive enhancer element and to block the transcriptional activation function AF-2 of ER-alpha. These results raise the possibility that wild-type BRCA1 suppresses estrogen-dependent transcriptional pathways related to mammary epithelial cell proliferation and that loss of this ability contributes to tumorigenesis.

BRCA1 Protein↗
PubMed1999

A comparative study of allometric scaling with plasma concentrations predicted by species-invariant time methods.

The objective of this study is to compare the empirical allometric approaches with species invariant time methods using equivalent time, kallynochron, apolysichron, and dienetichrons. Pharmacokinetic parameters (clearance, volume of distribution, and elimination half-life) of ethosuximide, cyclosporine and ciprofloxacin were scaled-up from animal data obtained from the literature. Two methods were utilized to generate plots for the prediction of clearance in humans: (i) clearance versus body weight (simple allometric equation); and (ii) the product of clearance and maximum life-span potential (MLP) versus body weight. Plasma concentrations of each of the drugs were predicted using elementary and complex Dedrick plots, equivalent time with an exponent of 0.25 and equivalent time with the exponent obtained from the plot of body weight and half-life. Plasma concentrations of cyclosporine and ciprofloxacin were also predicted by MLP normalization (dienetichrons). Almost similar results in the pharmacokinetic parameters of the tested drugs were obtained by the allometric approach and by the species invariant time methods.

Animals↗
PubMed1999

In vitro metabolic interaction studies: experience of the Food and Drug Administration.

A total of 194 new molecular entities approved by the Food and Drug Administration between 1992 and 1997 were surveyed to determine the role of in vitro metabolic interactions in the conduct of drug-drug interaction studies and to examine the methods used in these studies. Approximately 30% of the submissions were found to have in vitro metabolism-based interaction studies, most of which were inhibitory in nature. Chemical inhibition was the most commonly used approach in studying drug interactions in vitro. In this article, an attempt to assess the quality of the chemical inhibition approach was made. Four areas were found to be often overlooked: (1) incubation time and concentrations of the drug, (2) the difference between inhibition constant (k(i)) and 50% inhibitory concentration (IC50) values, (3) the substrate-dependent inhibition potential, and (4) the metabolic genotype or phenotype of the liver donor. We discuss the pitfalls in estimating drug interactions when these four areas are overlooked.

Cytochrome P-450 Enzyme Inhibitors↗
PubMed1999

FDA evaluations using in vitro metabolism to predict and interpret in vivo metabolic drug-drug interactions: impact on labeling.

Recent advances in in vitro metabolism methods have led to an improved ability to predict clinically relevant metabolic drug-drug interactions. To address the relationships of in vitro metabolism data and in vivo metabolism outcomes, the Office of Clinical Pharmacology and Biopharmaceutics in the Center for Drug Evaluation and Research, Food and Drug Administration, evaluated a number of recently approved new drug applications. The goal of these evaluations was to determine the contribution of in vitro metabolism data in (1) predicting in vivo drug-drug interactions, (2) determining the need to conduct an in vivo drug-drug interaction study, and (3) incorporating findings into drug product labeling. Ten cases are presented in this article. They fall into two major groups: (1) in vitro data were predictive of in vivo results, and (2) in vitro data were not predictive of in vivo results. Discussion of these cases highlights factors limiting predictability of in vivo metabolic interactions from in vitro metabolism data. The integration of these findings into drug product labeling is also discussed.

Data Collection↗
PubMed1999

Left atrial myxomas presenting with right hand weakness.

A 63-year-old man with multiple left atrial myxomas presenting with right hand weakness is described. Two-dimensional echocardiography obtained during the evaluation for his stroke showed a large left atrial mass. At surgery, two separate left atrial myxomas were excised. Pathology confirmed the diagnosis. Although left atrial myxomas are uncommon, they should be included in the differential diagnosis of stroke, especially in patients who present without cardiovascular or cerebrovascular risk factors. The absence of cardiac symptoms and signs does not rule out a cardiac myxoma.

Central Nervous System Diseases↗
PubMed1999

Pharmacokinetic and pharmacodynamic consequences of metabolism-based drug interactions with alprazolam, midazolam, and triazolam.

This review was conducted to identify the current data on drug interactions with alprazolam, midazolam, and triazolam to guide practitioners in the use of these drugs. The Medline electronic database from 1966 through 1998 was used to identify clinical studies of the pharmacokinetic effect of drugs on these three benzodiazepines. Of a total of 491 literature reports identified, 59 prospective studies met our selection criteria. The pharmacokinetic parameters of AUC, Cmax, t1/2, and tmax were evaluated for changes following an interaction. To allow comparison between studies, changes in the parameters were normalized relative to the control values. Pharmacodynamic effects and measures, when reported in the original studies as statistically significant, were classified as a strong interaction, and when the interaction was present but not statistically significant, they were classified as mild in this review. As a result, clinically significant drug interactions were noted for all three benzodiazepines, although it is clear that statistically significant pharmacokinetic changes do not always translate into clinically significant pharmacodynamic consequences. All three benzodiazepines were susceptible to drug interactions, but oral dosing of midazolam and triazolam resulted in greater alterations in the pharmacokinetic parameters than alprazolam due to their larger presystemic extraction. Ketoconazole and itraconazole were found to be the most potent metabolic inhibitors that prolonged the duration of or intensified the magnitude of the dynamic response produced by the three benzodiazepines. Rifampin, carbamazepine, and phenytoin were noted to be potent metabolic inducers, and their treatments result in loss of benzodiazepine therapeutic efficacy. In conclusion, potent metabolic inhibitors and inducers can either significantly prolong or diminish the dynamic effects of benzodiazepines via their influence on the pharmacokinetics of benzodiazepines.

Alprazolam↗
PubMed1998

Antibody-mediated modulation of Cryptococcus neoformans infection is dependent on distinct Fc receptor functions and IgG subclasses.

Coupling of an antibody response to effector cells through the Fc region of antibodies is a fundamental objective of effective vaccination. We have explored the role of the Fc receptor system in a murine model of Cryptococcus neoformans protection by infecting mice deleted for the common gamma chain of FcRs. Passive administration of an IgG1 mAb protects FcRgamma+/- mice infected with C. neoformans, but fails to protect FcRgamma-/- mice, indicating that the gamma chain acting through FcgammaRI and/or III is essential for IgG1-mediated protection. In contrast, passive administration of an IgG3 mAb with identical specificity resulted in enhanced pathogenicity in gamma chain-deficient and wild-type mice. In vitro studies with isolated macrophages demonstrate that IgG1-, IgG2a-, and IgG2b-opsonized C. neoformans are not phagocytosed or arrested in their growth in the absence of the FcRgamma chain. In contrast, opsonization of C. neoformans by IgG3 does not require the presence of the gamma chain or of FcRII, and the internalization of IgG3-treated organisms does not arrest fungal growth.

Animals↗
PubMed1998

Circulating mechanism of the "pure" venous flap: direct observation of microcirculation.

The circulating mechanism of the "pure" venous flap was studied via venography and direct observation of the microcirculation through transparent ear chambers and ear edges in a rabbit model. The flap, without arterial inflow, survived with normal hair growth and wound healing. Renewed blood circulation occurred 3 to 5 hr after transfer There were two typical flow patterns in the venules: one was a shaking movement with high frequency and short range; the other was a pendulum-like movement with low frequency and long range. The former was related to heart rate, while the later was not. The pendulum-like movement was the main flow responsible for perfusion of capillaries. Blood flow in the capillaries occurred 1 to 2 hr later than that in the venules. The pendulum-like flow perfused the capillaries in two ways: one was in the direction of venules to capillaries and then back to venules along the same route; the other was from venules to arterioles through arteriovenous shunts and then to capillaries. The first type of perfusion was gradually replaced by the second 2 days after transfer. There were extensive venous plexus flows in the flap, which lasted more than 4 weeks after transfer. Revascularized vessels ultimately supplied blood to the flap. The dynamic energy for the movement of blood at an early post-transfer stage was probably due to spontaneous venomotion.

Animals↗
PubMed1998

[The use of nasopharyngeal fiberoscope and obturator for treating velopharngeal incompetence].

OBJECTIVE: Using NPF and obturator to treat velopharyngeal incompetence. METHODS: Obturator was made based on the size of the velopharyngeal aperture determined with NPF. RESULTS: All of 45 cases was better in the velopharyngeal function, 15 cases (33%) had normal speech when the obturator was taken away after 2 years. CONCLUSION: This is a good conservative method for treating VPI of cleft palate postsurgery.

Adolescent↗
PubMed1998

[The reconstruction of mandible and soft tissue defects with the osteocutaneous free fibula flap].

OBJECTIVE: To find a new material to reconstruct the defects involving mandible and the surrounding soft tissues with the donor site morbidity mild and transient. METHODS: Ten consecutive fibula free flaps were used to reconstruct composite defect of mandible and soft tissue. The average length of the fibular graft was 9.1 cm, and the average size of the cutaneous-flap was 4.5 cm x 6.2 cm. RESULTS: 99mTcO4- scan demonstrated that 9 flaps were survivial (9/10) 2 weeks postsurgery. The function and the contour of the mandible were excellent. The donor site morbidity was mild and transient. CONCLUSION: Fibula has a high density of cortical bone. There is enough bone available to reconstruct mandible defect. The osteocutaneous fibula flap is a new material to reconstruct the composite mandible and soft tissue defects.

Adult↗