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C S Li

Publications and source records attributed to C S Li.

At least 37 records · Page 2Linked to original sources

Abbreviated tacrolimus area-under-the-curve monitoring for renal transplant recipients.

The area under the concentration time curve (AUC) for oral tacrolimus (FK) may provide a more precise model for FK monitoring after renal transplantation. The purpose of this study is to identify a simple, cost-effective method for predicting FK AUC. FK concentrations were measured at 0, 1, 2, 4, 6, 8, and 12 hours after the morning dose. The predicted AUCs (AUC(p)s) derived from regression equations were used to estimate the actual 12-hour AUCs (AUC(12)s). The relationship between AUC(p) and AUC(12) was validated by determining the coefficient of multiple determination (R(2)), percentage of prediction error (PE%), and percentage of absolute prediction error (APE%). Eighteen stable Oriental renal transplant recipients (9 men, 9 women) with a mean age of 42.6 +/- 6 years and mean body weight of 62.7 +/- 10 kg were recruited for the study. The FK AUC(12), trough, 2-hour, and 4-hour concentrations were 125 +/- 24 h. ng/mL (range, 87.7 to 181.9 h. ng/mL), 6 +/- 1.3 ng/mL, 18.1 +/- 4.7 ng/mL, and 11 +/- 2.4 ng/mL, respectively. Trough FK concentration did not have a significant correlation with AUC(12) (r = 0.34; P = 0.17). AUC(p) obtained by a two-time point regression equation using 2-hour (C2) and 4-hour (C4) FK concentrations: (AUC(P) = 16.2 + 2.4*C2 + 5.9*C4) obtained an R(2), PE%, and APE% of 0.93, -0.2% +/- 5.2% (range, -13% to 9.3%), and 3. 6% +/- 3.7% (range, 0.02% to 13%), respectively. We conclude that a two-point sampling method using C2 and C4 may be a more cost-effective FK monitoring strategy than morning FK trough levels in transplant recipients.

Administration, Oral↗

Airborne endotoxin exposure and the development of airway antigen-specific allergic responses.

BACKGROUND AND OBJECTIVE: Repeated exposure of aerosolized antigen via respiratory tract can induce immunoglobulin (Ig) E isotype-specific tolerance to this antigen. However, the atopic individuals often produce a higher titre of IgE in response to airborne environmental allergens. The mechanisms of this differential regulation of airway allergen-specific immune responses are not fully understood. This study investigated the role of airborne endotoxin on the initiation of antigen-specific airway allergic responses. METHODS: ELISA methods for detection of isotypes of antigen-specific antibodies and competitive reverse transcription polymerase chain reaction for detection mRNA of cytokines were used. In addition, Liu stain method was used to analyse the amounts of eosinophils in bronchoalveolar lavage fluid. RESULTS: Mice pre-exposed with airborne endotoxin mounted significantly higher amounts of OVA-specific IgE antibody responses to inhaled OVA than those OVA-only sensitized mice. Inhaled endotoxin could downregulate repeated airway antigen exposure-induced IgE isotype-specific tolerance and increase antigen-induced lung eosinophils infiltration. CONCLUSIONS: These data show that airborne endotoxin exposure could potentiate allergen-specific airway inflammation. The results should have potential implications for understanding the development of allergen-induced airway allergic responses.

Aerosols↗

Stability of urea and creatinine in spent hemodialysate.

Urea and creatinine levels in spent hemodialysates showed only small declines in spite of incubation at 37 degrees C for 36 hours. In the determination of dialysate-side solute removal, it would seem prudent to keep spent dialysate cold during collection to retard bacterial breakdown of these waste products.

Analysis of Variance↗

An airbone mold-derived product, beta-1,3-D-glucan, potentiates airway allergic responses.

Repeated inhalation of allergen leads to the down-regulation of allergen-specific IgE responses in non-atopic individuals as well as in mice. This phenomenon is named inhalation-induced IgE tolerance. In contrast, inhaled allergen causes significant IgE and allergic responses in atopic persons. The mechanisms involved in this differential regulation of airway allergen-specific immune responses remain unclear. Besides the allergen exposure of genetically susceptible individuals, environmental contamination is considered to play a role as an initiating factor for airway allergic responses. Using a murine model, we demonstrate here that airborne beta-1, 3-D-glucan, which exists frequently in our environment, particularly in highly humid areas, can abrogate inhalation-induced IgE isotype-specific down-regulation and promote airway eosinophil infiltration to inhaled antigen.

Administration, Inhalation↗

Comparison of double-bag and Y-set disconnect systems in continuous ambulatory peritoneal dialysis: a randomized prospective multicenter study.

We performed a multicenter, single-blinded, prospective randomized study on the use of a double-bag disconnect system (B) versus a Y-set disconnect system (Y). The peritonitis rate, exit site infection, clinical outcome, and patients' acceptance to the procedure were assessed. A total of 120 new end-stage renal failure patients of three regional hospitals were randomized: 60 each to the B and the Y systems. The results of 60 patients on the B system and 51 on the Y system were analyzable. They were followed up for a median of 16 months. Peritonitis rates for the B and the Y systems were 33.5 and 29.4 patient-months per episode, respectively. Exit site infection rates for the B and Y systems were 17.4 and 16.0 patient-months per episode, respectively. Four catheters were removed in each group. Patients on the B system were hospitalized for 2.1 days per patient per year related to peritonitis and exit site infection, and those on the Y system were hospitalized for 1.2 days. There was no significant difference between the B and Y systems in the incidences of peritonitis (all causes and those due to coagulase-negative staphylococci), exit site infection, and in hospitalization days. However, there was a higher percentage of gram-positive infections in the Y system (52%) than in the B system (32%) and a lower percentage of gram-negative infections in the Y system (16%) than in the B system (32%). Patients on the B system had a better acceptance of the procedure than patients on the Y system, as assessed by a six-item, 10-point questionnaire (total score, 43.1 +/- 10.2 v 37.6 +/- 9.4; P < 0.005 at 1 month; 44.6 +/- 9.1 v 39.8 +/- 8.6; P < 0.01 at 6 months). From this study, it is concluded that the B and Y systems are similar in the incidences of peritonitis and exit site infection, although the B system is better accepted by patients. This is probably the first multicenter randomized study comparing the double-bag and Y-set disconnect system using only new patients who had never used other systems of continuous ambulatory peritoneal dialysis.

Adult↗

Spontaneous renal allograft rupture attributed to acute tubular necrosis.

A renal allograft recipient receiving triple immunosuppressive therapy developed spontaneous allograft rupture 5 days after her second cadaveric renal transplantation. Renal biopsy showed interstitial edema with severe acute tubular necrosis (ATN). There was no evidence of acute rejection or renal vein thrombosis. The ruptured renal graft was salvaged by an aggressive fluid resuscitation therapy and surgical hemostasis. The renal function was satisfactory on discharge. We conclude that renal allograft rupture can be the result of interstitial edema solely attributed to ATN in the absence of graft rejection. The ruptured graft kidney is potentially salvageable for those patients whose hemodynamic status can be stabilized by appropriate supportive therapy.

Adult↗

Antisense down-regulation of thymidylate synthase to suppress growth and enhance cytotoxicity of 5-FUdR, 5-FU and Tomudex in HeLa cells.

1. Thymidylate synthase (TS), the key enzyme in de novo synthesis of thymidine, is an important target for antitumour chemotherapy. It was hypothesized that antisense oligonucleotide down-regulation of TS mRNA would decrease TS levels and enhance the cytotoxicity of inhibitors of TS, including the pyrimidine analogues 5-fluorouracil (5-FU) and 5-fluorodeoxyuridine (5-FUdR), and the folate analogue Tomudex (ICI D1694; N-(5-[N-(3, 4-dihydro-2-methyl-4-oxoquinazolin-6-ylmethyl)-N-methylamino ]-2-theon yl-L-glutamic acid). 2. 2'-Methoxyethoxylated, phosphorothioated 20-mer oligodeoxynucleotides (ODNs), complementary to various sequences in TS mRNA, were synthesized, along with control oligomers consisting of the same, respective bases in randomized order, against which all the biological effects were compared. Following a 6-h transfection of HeLa cells using polycationic liposome at 3 microg ml(-1), ODN 83 (50 nM), complementary to a region in the 3'-untranslated region of the TS mRNA, decreased TS mRNA levels by approximately 70% within 24 h. ODN 83 also decreased TS enzyme activity, as measured by binding of TS to radiolabelled 5-fluorodeoxyuridine monophosphate. In addition to inhibiting proliferation by up to approximately 40%, ODN 83 enhanced the cytotoxicity of Tomudex or 5-FU, added 1 day following transfection, by 50 - 60%. ODN 83 also enhanced sensitivity to 5-FUdR by 70%, but did not affect the toxicity of cisplatin, chlorambucil, melphalan, doxorubicin, ionizing radiation, paclitaxel, or irinotecan. 3. These data indicate that antisense ODN down-regulation of TS can inhibit human tumour cell proliferation and enhance the efficacy of TS-targeted drugs.

Antimetabolites, Antineoplastic↗

Effect of reversible inactivation of macaque lateral intraparietal area on visual and memory saccades.

Previous studies from our laboratory identified a parietal eye field in the primate lateral intraparietal sulcus, the lateral intraparietal area (area LIP). Here we further explore the role of area LIP in processing saccadic eye movements by observing the effects of reversible inactivation of this area. One to 2 microl of muscimol (8 mg/ml) were injected at locations where saccade-related activities were recorded for each lesion experiment. After the muscimol injection we observed in two macaque monkeys consistent effects on both the metrics and dynamics of saccadic eye movements at many injection sites. These effects usually took place within 10-30 min and disappeared after 5-6 h in most cases and certainly when tested the next day. After muscimol injection memory saccades directed toward the contralesional and upper space became hypometric, and in one monkey those to the ipsilesional space were slightly but significantly hypermetric. In some cases, the scatter of the end points of memory saccades was also increased. On the other hand, the metrics of visual saccades remained relatively intact. Latency for both visual and memory saccades toward the contralesional space was increased and in many cases displayed a higher variance after muscimol lesion. At many injection sites we also observed an increase of latency for visual and memory saccades toward the upper space. The peak velocities for memory saccades toward the contralesional space were decreased after muscimol injection. The peak velocities of visual saccades were not significantly different from those of the controls. The duration of saccadic eye movements either to the ipsilesional or contralesional space remained relatively the same for both visual and memory saccades. Overall these results demonstrated that we were able to selectively inactivate area LIP and observe effects on saccadic eye movements. Together with our previous recording studies these results futher support the view that area LIP plays a direct role in processing incoming sensory information to program saccadic eye movements. The results are consistent with our unit recording data and microstimulation studies, which suggest that area LIP represents contralateral space and also has a bias for the upper visual field.

Animals↗

Excitatory and inhibitory modulation of taste responses in the hamster brainstem.

The rostral portion of the nucleus of the solitary tract (NST) contains second-order gustatory neurons, sends projections to the parabrachial complex and brainstem reticular formation, and receives descending projections from several nuclei of the ascending gustatory pathway. Electrophysiological responses of NST neurons can be modulated by several factors, including blood glucose and insulin levels and taste aversion conditioning. We are using extracellular electrophysiological recording in vivo, combined with local microinjection of neurotransmitter agonists and antagonists, to study the mechanisms by which taste responses of cells in the hamster NST can be modulated. Afferent fibers of the chorda tympani (CT) nerve make excitatory synaptic contact with NST neurons; this excitation is probably mediated by the excitatory amino acid glutamate. Microinjection of kynurenic acid, a nonspecific glutamate receptor antagonist, into the NST completely and reversibly blocks afferent input from the CT nerve, produced by either anodal electrical or chemical stimulation of the anterior tongue. The non-NMDA ((RS)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/kainate) receptor antagonist 6-cyano-7-nitroquinoxaline-2, 3-dione (CNQX) also completely blocks gustatory input to these cells, whereas the N-methyl-D-aspartate (NMDA) antagonist DL-2-amino-5-phosphonovalerate (APV) produces only a small effect. There are many gamma-aminobutyric acid (GABA)-containing neurons within the NST and taste-responsive NST cells are maintained under a tonic GABAergic inhibition. Microinjection of the GABAA receptor antagonist bicuculline methiodide increases the taste responsiveness of NST neurons, whereas application of GABA inhibits taste responses in these cells. Preliminary data show that GABAergic inhibition can be produced by stimulation of the gustatory cortex. There are both intrinsic substance P (SP)-containing neurons and extrinsic SP-immunoreactive fibers in the rostral NST. Microinjection of SP into the NST enhances the responses of many NST cells to gustatory stimulation; NaCl-best neurons are preferentially excited by SP.

Animals↗

Determination of the solute removal index for urea by using a partial spent dialysate collection method.

In 22 hemodialysis patients, during a dialysis session, the solute removal index (SRI) for urea obtained from the use of a partial spent dialysate collection method was compared with that derived from the use of a total spent dialysate collection technique. The partial spent dialysate collection method was used to harvest a small representative sample of the total spent dialysate. The volumes of spent dialysate collected by the partial and the total spent dialysate collection methods were 1.7 +/- 0.4 L and 129.6 +/- 15.3 L, respectively. The total amount of urea nitrogen removed by dialysis as estimated by the partial spent dialysate collection method was similar to that determined by the total spent dialysate collection approach. As a result, the SRI value for urea obtained by the partial spent dialysate collection method (namely, 63% +/- 8%) correlated very well (r = 0.95, P < 0.001) with that derived by the total spent dialysate collection technique (namely, 62% +/- 8%). Our data suggest that it is feasible to use a simple partial spent dialysate collection method to obtain SRI results in patients treated with hemodialysis.

Female↗

Tonic GABAergic inhibition of taste-responsive neurons in the nucleus of the solitary tract.

The effects of gamma-aminobutyric acid (GABA) and the GABAA receptor antagonist bicuculline methiodide (BICM) on the activity of taste-responsive neurons in the nucleus of the solitary tract (NST) were examined electrophysiologically in urethane-anesthetized hamsters. Single neurons in the NST were recorded extracellularly and drugs (21 nl) were microinjected into the vicinity of the cell via a multibarrel pipette. The response of each cell was recorded to lingual stimulation with 0.032 M NaCl, 0.032 M sucrose, 0.0032 M citric acid and 0.032 M quinine hydrochloride (QHCl). Forty-six neurons were tested for the effects of GABA; the activity of 29 cells (63%) was inhibited by 5 mM GABA. Whether activity was elicited in these cells by repetitive anodal current stimulation (25 microA, 0.5 s, 0.1 Hz) of the tongue (n = 13 cells) or the cells were spontaneously active (n = 13 cells), GABA produced a dose-dependent (1, 2 and 5 mM) decrement in activity. Forty-seven NST neurons were tested for the effects of BICM on their responses to chemical stimulation of the tongue; the responses of 28 cells (60%) were enhanced by 10 mM BICM. The gustatory responses of 26 of these cells were tested with three concentrations (0.2, 2 and 10 mM) of BICM, which produced a dose-dependent increase in both spontaneous activity and taste-evoked responses. Nine of these neurons were sucrose-best, seven were NaCl-best, eight were acid-best and two responded best to QHCl. The responses to all four tastants were enhanced, with no difference among neuron types. For 18 cells that were tested with two or more gustatory stimuli, BICM increased their breadth of responsiveness to their two most effective stimuli. These data show that approximately 60% of the taste-responsive neurons in the rostral NST are inhibited by GABA and/or subject to a tonic inhibitory influence, which is mediated by GABAA receptors. The modulation of these cells by GABA provides a mechanism by which the breadth of tuning of the cell can be sharpened. Modulation of gustatory activity following a number of physiological changes could be mediated by such a GABAergic circuit.

Animals↗