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J Hsu

Publications and source records attributed to J Hsu.

At least 37 records · Page 2Linked to original sources

Metastable Equilibrium Solubility Distribution of Carbonated Apatite as a Function of Solution Composition.

Previous studies have shown that carbonated apatites (CAPs) exhibit the phenomenon of metastable equilibrium solubility (MES) in weak acid media. The purpose of the present investigation was to examine two questions: first, whether the MES concept is applicable to a broader range of solution conditions and, second, whether a driving force function associated with a surface complex having a constant stoichiometry governs the dissolution of CAP and, if so, what is this stoichiometry. CAP preparations with carbonate contents of 1.8-5.7 wt% (synthesized by hydrolysis of dicalcium phosphate anhydrate in solutions of varying bicarbonate levels or by direct precipitation from supersaturated calcium/phosphate/carbonate solutions) were studied as follows. MES distributions for each of the CAP preparations were determined by equilibrating the CAP under stirred conditions in a series of acetate buffers (0.10 M) containing various levels of calcium and phosphate in the pH range 4.5-6.5 and a solution calcium/phosphate ratio in the range 0.1-10. The amount dissolved in each instance was regarded as the fraction of the CAP possessing an MES value greater than that corresponding to the ion activity product (IAP) of the equilibrating solution. The solution IAPs were calculated from the solution compositions using plausible calcium phosphate stoichiometries, viz., dicalcium phosphate dihydrate, octacalcium phosphate, tricalcium phosphate, hydroxyapatite, carbonated apatite (based on the bulk composition of the particular CAP involved in the experiment), and tetracalcium phosphate. The fraction of CAP dissolved was plotted against the solution IAPs for each experimental set using each of the six assumed stoichiometries for the surface complex. The results demonstrated that the MES concept was applicable to all of the CAP preparations in media of various solution compositions and different pH levels. The most important new outcome of this study was that MES profiles for each of the CAP preparations in all of the experiments were found to be superimposable when solution IAPs were calculated using the hydroxyapatite stoichiometry, while such was not the case when other stoichiometries were used to calculate the solution IAPs. Copyright 1999 Academic Press.

Journal Article↗

p53 function influences the effect of fractionated radiotherapy on glioblastoma tumors.

PURPOSE: Glioblastoma multiforme brain tumors (GM) are treated with a spectrum of fractionation regimens based on the clinical and anatomical characteristics of the tumor but rarely based on the molecular characteristics of the individual neoplasm. This study tests the hypothesis that the response of cell lines derived from GM to fractionated radiotherapy depends on the function of wild-type p53 (wt p53), a tumor suppressor gene frequently mutated in GM tumors. METHODS & MATERIALS: Isogenic derivatives of glioblastoma cells differing only in p53 function were prepared using a retroviral vector expressing a dominant negative mutant of p53 (mt p53). Radiation survival in vitro was quantitated using linear quadratic and repair-saturation mathematical models. Apoptosis was assayed by a terminal deoxynucleotide transferase-labeling technique and chromatin morphology. RESULTS: We have previously reported the generation of isogenic GM cell lines differing only in p53 function. U87-175.4, lacking wt p53 function, had a significantly lower alpha/beta value than U87-LUX.8, expressing functional wt p53, leading us to hypothesize that fractionated irradiation would preferentially spare GM cells harboring mt p53 compared with those expressing functional, wt p53. Survival curves following either 2.0 Gy or 3.5 Gy/fraction demonstrated that lack of functional wt p53 was associated with resistance to fractionated irradiation. Radiation-induced apoptosis could not account for the observed differences in clonogenic survival. Rather, our data suggested that a deficit in the G1-checkpoint contributed to increased resistance to fractionated irradiation of cells expressing mutant p53. CONCLUSIONS: The effect of fractionated radiotherapy in GM may depend on the function of the tumor suppressor gene p53. A potential clinical consequence of these findings is that hyperfractionation regimens may provide a therapeutic advantage specifically for tumors expressing wt p53 whereas a radiotherapy course of fewer, larger fractions may be appropriate for the treatment of tumors carrying p53 mutations. Further studies are needed to confirm our proposal that the p53 status of GM tumors can be used to guide our choice of fractionation schemes.

Apoptosis↗

Relationships among carbonated apatite solubility, crystallite size, and microstrain parameters.

The use of the metastable equilibrium solubility (MES) concept to describe the solubility properties of carbonated apatites (CAPs) and human dental enamel (HE) has been well established in previous studies using a range of CAPs with varying carbonate contents and crystallinities. It was shown in these studies that the mean value of the CAP MES is directly related to the broadening parameter full width at half maximum (FWHM) of the 002 reflection of the X-ray diffraction profile. The apparent solubility of the CAPs increased monotonically with an increase in the broadening of the diffraction peaks, and when this peak broadening was taken into account, carbonate had no additional effect upon the MES. The broadening of the diffraction peaks has been used as an indicator of crystallinity, and is generally influenced by both crystallite size and microstrain. The purpose of the present study was to extract the crystallite size and microstrain parameters separately from the X-ray diffraction peaks and then to determine their relationships to the corresponding MES values. The samples studied were CAPs synthesized by precipitation from Ca(NO3)2 and NaH2PO4 solutions in carbonate containing media at temperatures of 95, 80, and 70 degrees C, and powdered HE. The crystallite size and microstrain parameters were determined simultaneously with the refinement of the structural parameters with the Rietveld method of whole-pattern-fitting structure-refinement. A modified pseudo-Voigt function was used to model the observed peak profiles. The MES distributions for the CAPs and HE were determined by a previously described method. The results of this study showed that the CAPs possessed an MES distribution and therefore provided further support that MES distribution is a common phenomenon, regardless of the method of CAP synthesis. The crystallite size decreased and the microstrain increased with increasing carbonate content and decreasing temperature of synthesis of the CAPs. A plot of the mean of the MES distribution versus the microstrain parameter showed that the apparent solubility of the CAPs and HE correlated very well with the microstrain parameter. On the other hand, a plot of the mean of the MES distribution versus the crystallite size parameter showed a poor correlation between MES and crystallite size. These findings support a view that microstrain, rather than crystallite size, is the dominant factor governing the effective solubility of the CAPs and dental enamel.

Apatites↗

The influence of renal function on the pharmacokinetics and pharmacodynamics and simulated time course of doxacurium.

UNLABELLED: Doxacurium's clearance (C1) is markedly decreased in patients with renal failure undergoing kidney transplantation. However, no studies have determined the influence of renal function (as assessed by creatinine clearance [CrCl]) on its pharmacokinetics in patients without renal failure. We studied 53 patients aged 19-59 yr. During N2O/isoflurane anesthesia, doxacurium was infused over 10 min, plasma was sampled for up to 6 h, and twitch tension was measured. A three-compartment model was fit to plasma concentration data and an effect compartment model to twitch data. Mixed-effects modeling was used to determine the influence of covariates, including CrC1, on doxacurium's pharmacokinetic/pharmacodynamic parameters. Obesity decreased both doxacurium's Cl (1.1% per percent above ideal body weight [IBW]) and its neuromuscular junction sensitivity (0.4% per percent above IBW). Cl increased 0.6% per mL/min increase in CrCl. In addition, the rate constant for equilibration between plasma concentration and effect decreased 46% per 1% increase in isoflurane, central compartment volume decreased 86% per 1% increase in isoflurane concentration, and slow distributional Cl decreased 69% per mg/ 100 mL increase in serum albumin. Simulations showed that the latter two covariates influence the time course of bolus doxacurium administration minimally. Both obesity and renal dysfunction prolong doxacurium's recovery markedly. When dosing is based on IBW, effects of CrCl on neuromuscular recovery are smaller compared with dosing based on actual weight. Therefore, obese patients should be dosed based on IBW. No further dosage adjustment is necessary for patients with renal dysfunction; however, recovery will take longer in patients with moderate-to-severe renal dysfunction. IMPLICATIONS: We examined the factors influencing doxacurium's pharmacokinetic and pharmacodynamic characteristics. Both creatinine clearance and obesity significantly influence its time course. The effect of obesity is minimized if patients are dosed based on ideal body weight.

Adult↗

Intramuscular rapacuronium in infants and children: dose-ranging and tracheal intubating conditions.

BACKGROUND: Intravenous rapacuronium's rapid onset and short duration suggest that intramuscular rapacuronium might facilitate tracheal intubation without prolonged paralysis. Accordingly, the authors injected rapacuronium into the deltoid muscle to determine the optimal dose and time for intubation in pediatric patients. METHODS: Unpremedicated patients (aged, 2 months to 3 yr) were studied. Part I: Spontaneous minute ventilation (V(E)) and twitch tension were measured during N2O/halothane anesthesia. Rapacuronium (2.2-5.5 mg/kg, given intramuscularly, n = 23), succinylcholine (4 mg/kg, given intramuscularly, n = 12), or vecuronium (0.1 mg/kg, given intravenously, n = 15) was given. Time to 50% depression of V(E) and 10% recovery of twitch were measured. Dose for each patient was changed 10-20% according to the previous patient's response. Part II: In 22 patients anesthetized with 0.82-1.0% halothane, the optimal rapacuronium dose determined in part I (infants, 2.8 mg/kg; children, 4.8 mg/kg) was given intramuscularly. Laryngoscopy was scored. Time to laryngoscopy was increased or decreased 0.5 min according to the previous patient's response. RESULTS: Part I: Rapacuronium typically depressed ventilation in < or = 2 min with 10% twitch recovery in 20-60 min. With succinylcholine, median time to ventilatory depression was 1.3 and 1.1 min for infants and children, respectively; for vecuronium, 0.7 and 0.6 min. Part I: Intubating conditions were good-excellent at 3.0 and 2.5 min in infants and children, respectively; time to 10% twitch recovery (mean +/- SD) was 31 +/- 14 and 36 +/- 14 min in the two groups. CONCLUSIONS: This pilot study indicates that deltoid injection of rapacuronium, 2.8 mg/kg in infants and 4.8 mg/kg in children, permits tracheal intubation within 2.5-3.0 min, despite a light plane of anesthesia. Duration of action is intermediate.

Child, Preschool↗

Cost analysis of revision total hip arthroplasty. A 5-year followup study.

A stratified, unselected sample of 30 patients who underwent revision total hip arthroplasty between 1990 and 1992 for whom complete clinical and financial data were available was studied. Clinical data included age, gender, diagnosis, length of stay, operative time and blood loss. Financial data included cost of implants, bone graft and accessories, hospital charge, and surgeon reimbursement. Results were compared with the results of an analogous group of 50 patients who underwent revision total hip arthroplasty at the same institution between 1995 and 1997. Cases were classified as simple (involving revision of only acetabular liner and/or femoral head), routine (revision of acetabular and/or femoral components), or complex (major structural graft, antiprotrusio cage, impacted grafting). For patients undergoing routine revision total hip arthroplasty, a dramatic decline of 52% occurred in length of stay during the 5-year span (10.7 days to 5.1 days). The average operative time also declined significantly (238 minutes to 199 minutes) as did the average implant cost ($4349 to $2827). Despite this, the average hospital charge increased 16% ($29,666 to $34,328). There was a significant and dramatic 35% decline in surgeon reimbursement ($3240 to $2178). There was no significant difference in surgeon reimbursement between simple, routine, and complex total hip arthroplasty. Patients who underwent complex procedures had a significantly greater length of stay (7.3 versus 5.1 days) and operative time (297 versus 199 minutes). The hospital charge was dramatically higher for patients undergoing complex procedures ($51,290 versus $34,328) but the surgeon reimbursement was lower on average, although not statistically significant ($1926 versus $2178). There was a significant increase in the number and complexity of revision total hip arthroplasties between the two periods. Significant decreases were achieved in length of stay, operating room time, and implant cost. Benefits from these changes were accrued to the hospital but not the surgeon because hospital costs decreased significantly whereas surgeon reimbursements declined dramatically.

Arthroplasty, Replacement, Hip↗

Impact of patient acuity on preference for information and autonomy in decision making.

OBJECTIVES: To test the hypotheses that ED patients' desires for medical information and for autonomy in decision making are inversely related to increasing acuity of illness, increasing age, and lower level of formal education. METHODS: The authors conducted a prospective study of ED patients who presented for care during seven nonconsecutive 24-hour periods. Of 804 patients approached, 665 completed a questionnaire that was administered by a trained research assistant. Patients rated their desire for medical information, and for participation in medical decision making, on two 10-cm visual analog scales. Patient acuity level was determined in routine fashion by trained triage nurses, who were unaware of the nature of this study. RESULTS: Desire for information was uniformly high, and did not vary statistically between triage groups (p = 0.41). The most acutely ill patients (level I) were more likely to be excluded by the research interviewer (p < 0.001). Of included level I patients, desire to participate was not decreased (p < 0.01). Higher level of formal education (p = 0.036) and younger age (p < 0.001) were associated with greater desire for autonomy in decision making. CONCLUSION: Among ED patients able to participate, higher acuity of illness was not associated with a decreased desire for medical information. Many very acutely ill patients preferred autonomy in medical decision making. Older patients and those with less formal education expressed a lesser desire for decision-making autonomy.

Adolescent↗

Pelvic reconstruction for severe periacetabular metastatic disease.

The functional outcome of acetabular reconstruction in 21 patients with severe acetabular deficiency was examined. The surgical indications were pain, immobility, and loss of indepedence. Surgical reconstruction included curettage, placement of an acetabular roof ring with screws crossing the defect, cementation of the defect, and cemented hip arthroplasty. Although three patients died within the first month, the mean postoperative survival was 14.5 +/- 4.0 months, with a 10.4 +/- 3.0-month period of independent living. Statistically significant postoperative improvements were seen in pain and mobility scores. Using the Musculoskeletal Tumor Society score for the lower extremity, a mean postoperative score of 14.2 of a total 30 was calculated. Low scores were attributed to the patients' overall disease, including the requirement of continued narcotic pain control, occupational restriction, and the presence of Trendelenburg limp. Surgical complications occurred in six patients and included three early postoperative deaths, two related to poor preoperative pulmonary function; two dislocations, one related to a late infection; one femoral nerve palsy; and one foot drop. Although associated with a high complication rate, acetabular reconstruction for metastatic disease can lead to marked improvement in pain control, function, independence, and quality of life in carefully selected patients.

Acetabulum↗

CD40-mediated signal transduction in human airway smooth muscle.

CD40 is a member of the TNF receptor family that was initially described on the surface of B cells. Recently, CD40 has also been described on mesenchymal cells, such as endothelial cells and fibroblasts, where engagement by its ligand CD40 ligand can lead to up-regulation of costimulatory and cell adhesion molecules, as well as secretion of proinflammatory cytokines. Since airway inflammation potentially involves cell-cell interactions of T cells and eosinophils (which express CD40 ligand) with airway smooth muscle (ASM) cells, we postulated that ASM may express CD40 and that engagement of ASM CD40 may modulate smooth muscle cell function. We demonstrate that CD40 is expressed on cultured human ASM and that expression can be increased by treatment with TNF-alpha or IFN-gamma. Cross-linking CD40 on ASM resulted in enhanced IL-6 secretion and an increase in intracellular calcium concentrations, which were dependent on calcium influx. We show that CD40-mediated signaling events include protein tyrosine phosphorylation and activation of NF-kappaB. Pretreatment of ASM with the tyrosine kinase inhibitors genistein or herbimycin inhibited the rapid mobilization of calcium induced via CD40, suggesting that calcium mobilization was coupled to activation of protein tyrosine kinases. In addition, inhibition of calcium influx inhibited both CD40-mediated NF-kappaB activation and enhancement of IL-6 secretion. These results delineate a potentially important CD40-mediated signal-transduction pathway in ASM, involving protein tyrosine kinase-dependent calcium mobilization, NF-kappaB activation, and IL-6 production. Together, these results suggest a mechanism whereby T cell/smooth muscle cell interactions may potentiate airway inflammation.

CD40 Antigens↗

Interleukin-10 inhibits cytokine synthesis in monocytes stimulated by titanium particles: evidence of an anti-inflammatory regulatory pathway.

The anti-inflammatory mediator interleukin-10 was investigated as a potential inhibitor of proinflammatory cytokine release in human peripheral blood monocytes activated with titanium particles. It inhibited the secretion of both tumor necrosis factor-alpha and interleukin-6 in a dose-dependent manner, with complete inhibition observed at 2 ng/ml. Co-culture experiments were performed to determine whether this cytokine may have functional importance as an inhibitor of the inflammatory response. When unstimulated lymphocytes and monocytes were co-cultured with titanium-stimulated monocytes, they significantly suppressed the secretion of both interleukin-6 and tumor necrosis factor-alpha. The inhibitory effect of these co-cultured cells could be partially blocked with the addition of an interleukin-10 neutralizing antibody. Interleukin-10 levels were measured in monocyte cultures treated with titanium particles as well as in fresh monocyte cultures treated with conditioned medium from titanium-stimulated monocytes. The latter experiments demonstrated marked stimulation of interleukin-10 secretion in conditioned medium-treated cultures, an effect that was related to the presence of tumor necrosis factor-alpha in the conditioned medium. The addition of titanium to conditioned medium-treated cultures markedly reduced the secretion of interleukin-10, suggesting that the most responsive cells are unstimulated monocytes exposed to agents released from activated monocytes. Altogether, the expression and responsiveness to interleukin-10 suggest a potential role for anti-inflammatory cytokines in regulation of the inflammatory response to wear debris.

Cells, Cultured↗

Gangliogenesis in leech: morphogenetic processes leading to segmentation in the central nervous system.

Using intracellular lineage tracers to study the main neurogenic lineage (N lineage) of the glossiphoniid leech embryo, we have characterized events leading from continuous columns of segmental founder cells (nf and ns primary blast cells) to discrete, segmentally iterated ganglia. The separation between prospective ganglia was first evident as a fissure between the posterior boundary of nf- and the anterior boundary of ns-derived progeny. We also identified the sublineages of nf-derived cells that contribute parallel stripes of cells to each segment. These stripes of cells project ventrolaterally from the dorsolateral margin of each nascent ganglion to the ventral body wall. The position and orientation of the stripes suggests that they play a role in forming the posterior segmental nerve; they are not coincident with the ganglionic boundary, and they form well after the separation of ganglionic primordia. Previous work has shown that cells in the anterior stripe express the leech engrailed-class gene. Thus, in contrast to the role of cells expressing engrailed in Drosophila, the stripes of N-derived cells expressing an engrailed-class gene in leech do not seem to play a direct role in segmentation or segment polarity.

Animals↗

Flux enhancement effects of ionic surfactants upon passive and electroosmotic transdermal transport.

This study focused upon the enhancement effects of ionic surfactants upon passive and electroosmotic transdermal flux. The first phase of the study involved validating theories relating surface properties of a membrane to electroosmotic solvent flow under appropriate experimental conditions using a synthetic model membrane (stack of 50 Nuclepore membranes). Numerical solutions to the Poisson-Boltzmann equation and the equations of fluid motion served as the theoretical basis for the experimental studies. Important outcomes of the model membrane studies were that electroosmotic solvent flow velocity was enhanced by the addition of an anionic surfactant, sodium dodecyl sulfate, and reversed by the addition of a cationic surfactant, dodecyltrimethylammonium bromide. The effective membrane pore wall surface charge densities were determined under a variety of experimental conditions. Adsorption of dodecyl sulfate to the pore wall increased the net negative charge on the pore wall. A reversal of the net pore wall surface charge density resulted from the adsorption of dodecyltrimethylammonium. The interrelationship between electroosmosis, surfactant adsorption, and ionic strength was also evaluated. The second phase of the study was an investigation of the effects of sodium dodecyl sulfate upon the transport of neutral polar permeants through human epidermal membrane (HEM). Fluxes of [14C]urea and [3H]sucrose were simultaneously measured across HEM samples under passive and 250 mV conditions; flux measurements were made before, during, and after HEM exposure to sodium dodecyl sulfate. A systematic analysis of the experimental data made it possible to elucidate the specific contributions of sodium dodecyl sulfate and the applied electric potential to the overall flux enhancement. Sodium dodecyl sulfate enhanced the intrinsic passive permeability of the HEM, and it also enhanced the contribution of electroosmosis to the flux during iontophoresis.

Humans↗

Combined effects of laser irradiation/solution fluoride ion on enamel demineralization.

OBJECTIVE: The effects of CO2 laser irradiation of dental enamel were evaluated in enamel demineralization experiments in partially saturated solutions (i.e., solutions containing both calcium and phosphate ions) with and without fluoride ions. SUMMARY BACKGROUND DATA: Previous studies had shown that a continuous-wave CO2 laser at an energy density of around 130 J/cm2 may induce an increased acid resistance in human dental enamel as assessed by exposure to severe demineralization conditions (0.1 mol/L acetate buffer, pH 4.5 and ionic strength 0.5 mol/L). METHODS: Enamel blocks were irradiated with a continuous-wave CO2 laser at a wavelength of 10.6 microns using energy densities of from 42.5 to 170.0 J/cm2. The blocks were then exposed to a partially saturated demineralizing solution with or without 0.2 ppm fluoride at a temperature of 30 degrees C for 24 hours. The demineralization was examined both qualitatively by light microscopy and quantitatively by microradiography. RESULTS: A comparison between the lased and the unlased portions of enamel showed increased acid-resistance with increasing laser energy density and, at the highest energy density of 170.0 J/cm2, there was little or no lesion development in the fluoride-free dissolution medium. The demineralization of enamel was reduced dramatically in the presence of 0.2 ppm fluoride for both lased and unlased enamel; there was only modest lesion development observed for unlased enamel and, at an energy density as low as 85.0 J/cm2, the surface of enamel was found to be completely protected. CONCLUSIONS: These findings are consistent with the mechanism that laser irradiation of dental enamel results in significant reduction of the effective solubility of enamel mineral and that there is a significant synergism between laser irradiation and solution fluoride with regard to this effect.

Carbon Dioxide↗