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Biomedical subjects

H Ko

Publications and source records attributed to H Ko.

At least 19 recordsLinked to original sources
PubMed2006

Acute fatty liver of pregnancy.

Acute fatty liver of pregnancy (AFLP) is a rare, potentially fatal complication that occurs in the third trimester or early postpartum period. Although the exact pathogenesis is unknown, this disease has been linked to an abnormality in fetal fatty acid metabolism. Early diagnosis of AFLP sometimes can be difficult because it shares features with other common conditions such as pre-eclampsia, viral hepatitis and cholestasis of pregnancy. However, a careful history and physical examination, in conjunction with compatible laboratory and imaging results, are often sufficient to make the diagnosis, and liver biopsy is rarely indicated. Supportive care and expeditious delivery are essential to optimal maternal-fetal outcomes and remain as the mainstay treatment for AFLP.

Acute Disease↗
PubMed2001

Mild postischemic hypothermia is neuroprotective in the immature rat neocortex slice.

Mild hypothermia as an intervention after perinatal asphyxia may prevent neurological damage in the newborn. We used stimulus-induced field potentials to monitor recovery from oxygen and glucose deprivation (OGD) in neocortex slices of 6-8-day-old wistar rats. OGD after a latency of 10.7+/-2.1 min (mean+/-S.E.) resulted in an anoxic depolarisation with an amplitude of 5.4+/-2.4 mV. Mild hypothermia of 31 degrees C (vs. 35 degrees C in the control group) was applied for 60 min after end of OGD. The 20, 40, 60 and 80% recovery of the field potential amplitude was significantly faster in the hypothermia group in comparison to the control group. These data indicate that mild postischemic hypothermia may have neuroprotective effects after perinatal asphyxia.

Animals↗
PubMed2000

Trace element homeostasis during continuous sedation with propofol containing EDTA versus other sedatives in critically ill patients.

OBJECTIVE: To evaluate changes in serum and urinary zinc, cobalt, copper, iron, and calcium concentrations in critically ill patients receiving propofol containing disodium edetate (disodium ethylenediaminetetraacetic acid [EDTA]) versus sedative agents without EDTA. DESIGN: This was a randomised, open-label, parallel-group study with randomisation stratified by baseline Acute Physiology and Chronic Health Evaluation (APACHE II) scores. SETTING: Intensive care units (ICU) in 23 medical centres. PATIENTS: Medical, surgical, or trauma ICU patients 17 years of age or older who required mechanical ventilator support and sedation. INTERVENTIONS: A total of 106 patients received propofol containing 0.005 % EDTA (propofol EDTA), and 104 received other sedative agents without EDTA (non-EDTA). Only the first 108 patients were assessed for urinary trace metal excretion. Twenty-four-hour urine samples were collected on days 2, 3, and 7 and every 7 days thereafter for determination of zinc, cobalt, copper, iron, and calcium excretion; EDTA levels; urine osmolality; albumin levels; and glucose levels. The first 143 patients were assessed for serum concentration of zinc, cobalt, copper, iron, and calcium; creatinine; blood urea nitrogen; and albumin at baseline and once during each 24-hour urine collection. MEASUREMENTS AND RESULTS: For the assessment of trace metals, patients receiving propofol EDTA demonstrated increased mean urinary excretion of zinc, copper, and iron compared with the normal range. All patients receiving sedatives demonstrated increased urinary excretion of zinc and copper above normal reference values. Compared with the non-EDTA sedative group, the propofol EDTA group demonstrated increased urinary excretion of zinc and iron. Mean serum concentrations of zinc and total calcium were decreased in both patient groups. Serum zinc concentrations increased from baseline to day 3 in the non-EDTA sedative group but not in the propofol EDTA group. Renal function, measured by blood urea nitrogen, serum creatinine, and creatinine clearance, did not deteriorate during ICU sedation with either regimen. CONCLUSION: This study showed that critical illness is associated with increased urinary losses of zinc, copper, and iron. Propofol EDTA-treated patients had greater urinary losses of zinc and iron and lower serum zinc concentrations compared with the non-EDTA sedative group. No adverse events indicative of trace metal deficiency were observed in either group. The clinical significance of trace metal losses during critical illness is unclear and requires further study.

APACHE↗
PubMed2000

Fetal renal volume in normal gestation: a three-dimensional ultrasound study.

To establish a reference chart of fetal kidneys in normal pregnancy, we performed a prospective and cross-sectional study. A total of 152 singleton fetuses ranging between 20 and 40 weeks' gestation and meeting the criteria of normal pregnancies were included. Three-dimensional ultrasound (3-D US) was used to measure the fetal renal volume. Our results revealed that both renal volumes are highly correlated with the fetal gestational age. Using gestational age (GA) as the independent variable and right renal volume (RRV) as the dependent variable, the best-fit regression equation was RRV (mL)=0.74053xGA (week)-13.318 (r = 0.89, p < 0.001). Similarly, the best-fit equation for the left renal volume (LRV) was LRV (mL)=0. 76093xGA (week)-13.421 (r = 0.86, p < 0.001). The normal growth centiles of both kidneys were established based on these two equations. There were no significant differences of the volumes between bilateral kidneys. In conclusion, our data of fetal renal volumes assessed by 3-D US may serve as a reference in evaluating fetal renal growth.

Cross-Sectional Studies↗
PubMed2000

Correcting for measurement error in individual-level covariates in nonlinear mixed effects models.

The nonlinear mixed effects model is used to represent data in pharmacokinetics, viral dynamics, and other areas where an objective is to elucidate associations among individual-specific model parameters and covariates; however, covariates may be measured with error. For additive measurement error, we show substitution of mismeasured covariates for true covariates may lead to biased estimators for fixed effects and random effects covariance parameters, while regression calibration may eliminate bias in fixed effects but fail to correct that in covariance parameters. We develop methods to take account of measurement error that correct this bias and may be implemented with standard software, and we demonstrate their utility via simulation and application to data from a study of HIV dynamics.

Biometry↗
PubMed1992

Significance of serum type-IV collagen levels in various liver diseases. Measurement with a one-step sandwich enzyme immunoassay using monoclonal antibodies with specificity for pepsin-solubilized type-IV collagen.

Serum type-IV collagen levels determined with a one-step sandwich enzyme immunoassay (EIA) using monoclonal antibodies with specificity for pepsin-solubilized type-IV collagen were compared with histologic changes in liver biopsy specimens from 107 patients with various liver diseases. Serum type-IV collagen levels were increased in the groups with liver diseases compared with controls. The serum type-IV collagen levels in the group with alcoholic cirrhosis showed significantly higher values than the other groups (P less than 0.05). A significant positive correlation was found between the serum type-IV collagen level and the degree of fibrosis or cell infiltration in 107 patients. Immunolocalization of type-IV collagen was observed around blood vessels and bile ducts increased in number in the portal tracts, with cell infiltration and fibrosis, increased around vessels in fibrous septa, and sinusoidal walls of areas with cell infiltration or necrosis in hepatic lobules, and along the boundary between fibrous septa and hepatocytes. The present data indicate that serum type-IV collagen may be a sensitive marker for active fibrosis and that the elevation of serum type-IV collagen level primarily reflects the enhancement of type-IV collagen synthesis and deposition in the liver tissue at the stage of active fibrosis in liver disease.

Adolescent↗
PubMed1990

Fast-LC determination of 1-methyl-1H-tetrazole-5-thiol in human plasma with column-switching sample clean-up.

A simple, fast and sensitive method for the quantitative determination of 1-methyl-1H-tetrazole-5-thiol using HPLC is reported. Samples are deproteinated by plasma water filtration and injected into a HPLC system capable of column switching and backflushing the analytical column. The limit of quantitation was determined to be 70 ng ml-1 and the limit of detection 22 ng ml-1. Between-day precision (expressed as percent coefficient of variation) of standard curve slopes was +/- 3.5% with a range of within-day percent coefficient of variations from 0.28 to 1.4%. Recovery and precision of spiked control samples was 96 +/- 7% over a concentration range of 630-6300 ng ml-1.

Calibration↗
PubMed1990

Disposition of cefmetazole in healthy volunteers and patients with impaired renal function.

The disposition of cefmetazole was studied in 25 subjects with various degrees of renal function after a 1,000-mg, constant-rate, 30-min intravenous infusion of cefmetazole sodium. In six subjects with creatinine clearance (CLCR) of greater than 90 ml/min per 1.73 m2 (group 1), the terminal elimination half-life (t1/2 beta) was 1.31 +/- 0.54 h (mean +/- standard deviation), cefmetazole total body clearance (CLP) was 132.8 +/- 25.1 ml/min per 1.73 m2, and volume of distribution at steady state was 0.165 +/- 0.025 liter/kg. The fraction of dose excreted unchanged in the urine was 84.0% +/- 26.1%. Subjects with CLCRS of 40 to 69 (group 2, n = 6) and 10 to 39 (group 3, n = 6) ml/min per 1.73 m2 demonstrated prolongation of the t1/2 beta (3.62 +/- 1.06 and 5.93 +/- 1.81 h, respectively) and significant reductions in cefmetazole CLP (52.8 +/- 14.3 and 30.2 +/- 10.2 ml/min per 1.73 m2, respectively), compared with group 1. In seven subjects on chronic hemodialysis (group 4) studied during an interdialytic period, the cefmetazole t1/2 beta was increased to 24.10 +/- 8.12 h and the CLP was reduced to 6.8 +/- 2.1 ml/min per 1.73 m2. Cefmetazole CLP correlated positively with CLCR (r = 0.951, P less than 0.001): CLP = (1.181 . CLCR) -- 0.287. The disposition of cefmetazole was also assessed in six group 4 subjects during an intradialytic period. The t1/2 beta during hemodialysis (2.09 +/- 0.69 h) was significantly shorter than that observed during the interdialytic period. The hemodialysis clearance of cefmetazole was 86.1 +/- 20.1 ml/min, and the fraction of cefmetazole removed during hemodialysis was 59.8% +/- 5.9%. It is recommended that patients with renal insufficiency received standard doses of cefmetazole at extended intervals and patients on maintenance hemodialysis received standard doses after hemodialysis.

Adolescent↗
PubMed1989

Pharmacokinetics of intravenously administered cefmetazole and cefoxitin and effects of probenecid on cefmetazole elimination.

Sixteen healthy male volunteers participated in a randomized, balanced, three-way crossover study comparing the pharmacokinetics of cefmetazole, cefoxitin, and cefmetazole with probenecid pretreatment. Single 2-g doses of cefmetazole sodium and cefoxitin sodium were given intravenously as a 5-min infusion. Concentrations of cefmetazole and cefoxitin were determined by using a specific semiautomated high-performance liquid chromatographic method. Concentration-time profiles of cefmetazole and cefoxitin declined in a biexponential manner from peak levels. Compared with cefoxitin, cefmetazole had a significantly (P less than 0.05) higher mean (+/- standard error of the mean) peak concentration in serum (290 +/- 11 versus 244 +/- 10 micrograms/ml), a longer terminal disposition half-life (1.50 +/- 0.14 versus 0.81 +/- 0.04 h), lower systemic clearance (111.7 +/- 4.7 versus 279 +/- 12 ml/min) and renal clearance (78.7 +/- 4.3 versus 221 +/- 14 ml/min) of intact drug, and a slightly smaller steady-state volume of distribution (10.3 +/- 0.21 versus 12.8 +/- 0.48 liters). Mean recoveries of cefmetazole and cefoxitin in urine were approximately 71 and 77%, respectively. Pretreatment of volunteers with probenecid (1 g orally) significantly (P less than 0.05) increased concentrations of cefmetazole in serum 1 h after drug administration without significantly increasing maximum concentrations in serum. Mean areas under the concentration-time curve (466 +/- 27 versus 295 +/- 13 micrograms.h/ml) and terminal disposition half-lives (2.27 +/- 0.13 versus 1.50 +/- 0.14 h) of cefmetazole increased. Systemic clearance (72.1 +/- 4.0 versus 111.7 +/- 4.7 ml/min) and renal clearance (47.4 +/- 4.0 versus 78.7 +/- 4.3 ml/min) of intact antibiotic decreased. Mean recoveries (65.9 +/- 3.7 versus 71.0 +/- 3.2%) of intact cefmetazole in urine were not significantly (P > 0.05) different. Elimination of cefmetazole in urine was also significantly prolonged by probenecid, with substantial concentrations of cefmetazole (>/= 20 micrograms/ml) found in the 12- to 24-h urine collection for 14 to 16 volunteers. The results show that cefmetazole remains at clinically relevant concentrations (1 to 2 micrograms/ml) approximately twice as long as cefoxitin, that serum cefmetazole can be maintained longer at clinically significant concentrations with preadministration of probenecid, and that cefmetazole is partially eliminated by renal tubule secretion.

Adult↗
PubMed1989

Pharmacokinetics of single-dose cefmetazole following intramuscular administration of cefmetazole sodium to healthy male volunteers.

The tolerance and pharmacokinetics of cefmetazole were studied in healthy male volunteers who received a placebo (sterile saline) or a single dose of cefmetazole sodium intramuscularly. Drug-treated volunteers received one of four doses, 0.375, 0.750, 1, or 2 g. The drug was well tolerated, with no adverse medical events or laboratory changes observed during the study that could affect the pharmacokinetic interpretation of the data. Cefmetazole concentrations were determined by using a specific high-performance liquid chromatographic method. Serum cefmetazole concentrations were well described by a one-compartment open model with first-order absorption and elimination. Cefmetazole was rapidly absorbed in most volunteers, with a mean time to maximum concentration in serum of 1.24 +/- 0.12 h (+/- standard error of the mean), and the mean maximum concentration in serum increased from 17.0 +/- 1.6 to 74.2 +/- 9.5 micrograms/ml over the 0.375- to 2-g dose range. Maximum concentrations in serum, areas under serum concentration-time curve, and urinary excretion of intact drug increased in proportion to cefmetazole sodium dose. Times at which maximum concentrations in serum occurred, apparent volumes of distribution, steady-state volumes of distribution, absorption and elimination half-lives, and systemic clearances did not change significantly (P greater than 0.05) with drug dose. Although absorption and elimination half-lives were not significantly different in 10 of 40 volunteers (P greater than 0.05), in a majority of subjects elimination half-lives were approximately 10 times longer than absorption half-lives. The mean recovery of intact drug in urine ranged from 68.8 to 86.0% over the dose range studied, with a mean recovery over all doses of 77.1 +/- 2.4%. Rental clearances were significantly lower (P < 0.05) for the two lowest doses (93.0 and 84.3 versus 115.0 and 118.0 ml/min); these differences are not considered clinically important. The results of this study indicate that cefmetazole pharmacokinetics are linear after administration of single intramuscular doses ranging from 0.375 to 2 g, that clinically relevant concentrations of cefmetazole in serum (1 to 2 micrograms/ml) persist in a majority of volunteers for more than 8 h after administration of 0.750-g or higher doses, and that clinically relevant concentrations of cefmetazole continue to be excreted in urine 8 to 12 h after administration of 0.375- to 2-g doses.

Adolescent↗
PubMed1989

B cell suppressing and CD8+ T cell enhancing effects of photosensitive dye platonin in humans.

Platonin is one of the photosensitive dyes of trithiazole pentamethine cyanine. It is used as an effective medicine for rheumatoid arthritis. In our study, platonin suppressed the immunoglobulin (Ig) production of human peripheral blood lymphocytes (PBL) stimulated by Staphylococcus aureus Cowan I (SAC) or pokeweed mitogen (PWM). It also suppressed the PWM induced Ig production of B cells when T cells and/or B cells were pretreated with platonin, respectively. The percentage of CD8+ T cells was increased by platonin. Our results suggest that platonin suppresses Ig production through suppressing B cells and enhancing CD8+ (suppressor/cytotoxic) T cells.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1982

Reactivity of cold agglutinins with subsets of human lymphocytes of various origins.

Forty-five cold agglutinins (CA) were tested against various populations of lymphocytes by cytotoxicity and immunofluorescence assays. Marked differences were observed between anti-I and anti-i CA. Thirty-six per cent of anti-I killed preferentially peripheral blood and tonsillary B lymphocytes, whereas only 12 per cent killed preferentially T lymphocytes. Anti-I killed a much higher proportion of B-chronic lymphocytic leukemia cells than peripheral blood lymphocytes, peripheral blood B cells or T-chronic lymphocytic leukemia cells. Forty-three per cent of anti-i killed preferentially peripheral blood T lymphocytes and 54 per cent killed preferentially tonsillary T cells, whereas only 14 per cent killed more peripheral blood B cells and none killed preferentially tonsillary B cells. The kill of thymic lymphocytes and T-chronic lymphocytic leukemia cells by anti-i was very high, whereas the kill of B-chronic lymphocytic leukemia cells was very low. Almost all CA of other than I-i specificities showed preferential kill of peripheral blood B (83 per cent) and tonsillary B (67 per cent) cells. Tonsillary lymphocytes were usually more susceptible to the cytotoxic activity of CA than peripheral blood lymphocytes. Cold agglutinins with kappa light chains killed more B cells whereas CA with gamma light chains seemed to kill more T cells. Cytotoxicity did not correlate to the utilization of complement. It is suggested that the density and/or the accessibility of membranous antigens may be different on B and T cells, or alternatively that in addition to antigens common to all lymphocytes, anti-I and non-I/i cold agglutinins recognize specific antigenic determinants on B lymphocytes, whereas anti-i cold agglutinins recognize specific antigenic determinants on T lymphocytes.

Agglutinins↗