Search PubMed⌕ Search

Biomedical subjects

A Lau

Publications and source records attributed to A Lau.

At least 91 records · Page 5Linked to original sources

Comparison of EMIT versus bioassay to evaluate inactivation of tobramycin by piperacillin.

We evaluated and compared the sensitivity of enzyme multiplied immunoassay (EMIT) and bioassay techniques in detecting the degree of inactivation of tobramycin by piperacillin in serum specimens. Specimens were prepared to contain initial tobramycin concentrations of 10 micrograms/ml and piperacillin concentrations of 62.5, 125.0, 250.0, and 500 micrograms/ml. The samples were stored at room temperature (25 degrees C), in the refrigerator (4 degrees C), and in the freezer (-10 degrees C) for up to 7 days. Tobramycin concentrations were determined by the two assay methods at the conclusion of 1, 3, and 6 h and 1, 3, 5, and 7 days of storage. The percentage of tobramycin activity as measured by EMIT and bioassay differed throughout the study period. Statistical analysis revealed that the assay method was the only significant variable to contribute to the variability observed in the differences of tobramycin concentration. Our results suggest that the bioassay technique is more sensitive than the EMIT assay for detecting the degree of inactivation of tobramycin by piperacillin. The EMIT assay overestimates tobramycin concentrations, which may be due to measurement of active and inactive tobramycin.

Analysis of Variance↗

Cell-to-cell interaction of Streptococcus sanguis and Propionibacterium acnes on saliva-coated hydroxyapatite.

Cell-to-cell interaction (coaggregation) between Propionibacterium acnes PK93 and Streptococcus sanguis DL1 was measured on saliva-coated hydroxyapatite beads (SHA) at bacterial concentrations between 1.3 X 10(6) and 6.7 X 10(8) cells per ml. Four hundredfold more DL1 than PK93 cells adhered to the saliva-coated beads, and the adherence of S. sanguis was proportional to cell input. SHA precoated with 3 X 10(8) DL1 cells bound 75 to 80% of available PK93 cells at all input amounts tested, up to an input of 8 X 10(7) cells. Adherence of PK93 to DL1-coated SHA approached saturation at an input of approximately 10(9) PK93 cells, when 1.5 X 10(8) bound. The coaggregation on SHA occurred either in buffer or saliva and was inhibited by N-acetylgalactosamine and by lactose; the attachment of DL1 to SHA was not inhibited by these sugars. S. sanguis 34 and heat-treated DL1 cells, neither of which form coaggregates with PK93, attached to SHA, but such cells did not bind PK93 cells. The findings of this study indicate that bacteria unable to attach to saliva-coated hydroxyapatite can indeed adhere to such a surface by strong lectin-mediated cell-to-cell interactions with bacteria already attached to the surface.

Acetylgalactosamine↗

Atrial natriuretic peptide, right atrial pressure, and sodium excretion rate in the rat.

This study examined the relationship between right atrial pressure (RAP), urine flow rate, sodium excretion rate, and plasma atrial natriuretic peptide (ANP) levels after an acute Ringer expansion. Two groups of rats had their RAP monitored and balloon catheters placed in their thoracic inferior venae cavae. In one group the balloon remained deflated, and in the second group the balloon was inflated during the volume expansion in an attempt to prevent the rise in RAP. The peak RAP was 7.3 +/- 0.8 mmHg when the balloon remained deflated and 3.5 +/- 0.6 mmHg in the group with the balloon catheter inflated (P less than 0.005). The corresponding peak ANP levels were 682 +/- 140 and 223 +/- 40 pg/ml. There was a significant correlation between the peak RAP and ANP levels (r = 0.754; P less than 0.05). The inflation of the balloon catheter significantly decreased the urine flow rate and the urine sodium excretion rate. A final group of animals had 200 microliters of rabbit serum containing antibody to ANP infused before the volume expansion. The antibody-treated animals had significantly lower urine flow and sodium excretion rates than nonantibody-treated control rats. We conclude that ANP is one of the factors which allows the rat to excrete an acute Ringer expansion.

Animals↗

Pharmacokinetics of metronidazole in hospitalized patients.

The recently expanded indications of metronidazole increase the use of the drug in the hospitalized patients. However, most of the pharmacokinetic information on metronidazole was derived from normal subjects. The pharmacokinetics of metronidazole was, therefore, evaluated in nine hospitalized patients who have no evidence of liver or kidney failure. The patients received the drug for prophylaxis or treatment of infectious conditions. Serial blood samples were obtained from the patients and serum metronidazole concentrations were determined by high performance liquid chromatography. The following pharmacokinetic parameters (mean +/- standard deviation) were obtained: half-life = 10.2 +/- 3.1 hours, elimination rate constant = 0.075 +/- 0.026 hour-1, volume of distribution = 0.65 +/- 0.25 l kg-1, and total body clearance = 0.048 +/- 0.024 l h-1 kg-1. The mean value of these parameters are not substantially different from those obtained in the normal subjects. However, a higher interpatient variation was found in the hospitalized patients. The heterogeneity of health condition, body composition, fluid balance, hemodynamics and nutritional status may all contribute to the variability in pharmacokinetic characteristics.

Adult↗

Pharmacokinetics of piperacillin in hospitalized patients.

Piperacillin is an extended-spectrum penicillin active against Pseudomonas. It has been documented to be effective in the treatment of complicated urinary tract infections and urosepsis. Much of the pharmacokinetic information available is obtained from normal subjects. The purpose of this study is to evaluate piperacillin pharmacokinetics in hospitalized patients. Ten clinically stable hospitalized urology patients were given 4 grams of piperacillin intravenously in a single dose. Serial blood samples were then obtained and serum piperacillin concentrations were determined by high performance liquid chromatography. The following pharmacokinetic parameters (mean +/- SD) were determined: half-life = 1.09 +/- 0.31 h, elimination rate constant = 0.69 +/- 0.22 h-1, volume of distribution = 0.36 +/- 0.13 l/kg, total body clearance = 0.230 +/- 0.054 l/h/kg. These parameters are comparable to those obtained in normal subjects except for the volume of distribution which is slightly higher than that reported in healthy volunteers. Pharmacokinetic information obtained in healthy subjects may, therefore, be applied to the clinically stable hospitalized urology patient. However, changes in pharmacokinetic characteristics may be found in the critically ill patient with compromise in hemodynamics and significant third spacing of fluid.

Adult↗

Effect of piperacillin on tobramycin pharmacokinetics in patients with normal renal function.

Aminoglycosides are inactivated by extended-spectrum penicillins in vitro and in patients with end-stage renal failure. In this prospective controlled study, we determined the effect of piperacillin on tobramycin pharmacokinetics. In 10 clinically stable male patients with calculated creatinine clearances of greater than or equal to 60 ml/min, serial levels in serum of tobramycin alone and after single 4-g intravenous doses of piperacillin were determined. No statistically significant changes in the concentration of drug in serum, the half-life (t1/2), the elimination rate constant (Ke), the volume of distribution (Vd), or the area under the serum concentration-time curve (AUC0-oo) occurred when tobramycin was used concurrently with piperacillin. Therefore, this antibiotic combination will not result in a clinically significant interaction in patients with normal renal function.

Adult↗

Kinetics of elementary steps in the cytochrome P-450 reaction sequence. V. Laser temperature-jump investigation of the spin relaxation kinetics of cytochrome P-450 LM2.

The cytochrome P-450 LM2 spin state relaxation kinetics has been resolved by means of laser temperature-jump techniques. The first order rate constants amount to about 10(6) S-1 in the substrate-free and the substrate-bound protein, respectively. Evidence is provided that the spin equilibrium preequilibrates the P-450 reduction but is not rate-limiting. Additional capacitor discharge temperature-jump studies elucidate substrate dependent perturbations.

Animals↗

The adsorption of divalent cations to phosphatidylglycerol bilayer membranes.

The ability of Stern equation to describe the adsorption of divalent cations to phosphatidylglycerol membranes was tested by combining 31P-NMR and electrophoretic mobility measurements. In 0.1 M sodium chloride both the 31P-NMR and the zeta potential data are well described by the Stern equation. 31P-NMR and 13C-NMR results indicate that cobalt forms inner-sphere complexes only with the phosphate group of phosphatidylglycerol molecules and that a substantial fraction of the adsorbed cobalt ions form outer-sphere complexes. Evidence is presented that suggests the alkaline earth cations also bind to phospholipids mainly by forming outer sphere complexes. Electrophoretic mobility measurements were performed with several different divalent cations. In all cases the zeta potentials in 0.1 M sodium chloride were well described by the Stern equation. The intrinsic 1:1 association constants (M-1) for the phosphatidylglycerol complexes decreased in the sequence: Mn2+, 11.5; Ca2+, 8.5; Ni2+, 7.5; Co2+, 6.5; Mg2+, 6.0; Ba2+, 5.5 and Sr2+, 5.0.

Adsorption↗

Effect of surfactant on tetracycline absorption across everted rat intestine.

Absorption of tetracycline hydrochloride (500 micrograms/ml) from oxygenated modified Krebs buffer in randomized everted rat jejunal segments was determined alone and in the presence of calcium, polysorbate 80, and calcium plus polysorbate 80. Surfactant increased absorption of tetracycline in the presence and absence of calcium, with 0.01% (w/v) polysorbate 80 increasing transfer to the greatest extent of the concentrations examined(0.005, 0.01, 0.05, 0.1, and 1%); tetracycline hydrochloride + 12.5 mM CaCl2, 143 +/- 45 micrograms/ml; tetracycline hydrochloride + polysorbate 80, 389 +/- 18 micrograms/ml; tetracycline hydrochloride + 12.5 mM CaCl2 + polysorbate 80, 255 +/- 31 micrograms/ml. On the premise that the effective surfactant concentration is similar to the critical micelle concentration, an absorption mechanism based on micellar solubilization is postulated.

Animals↗

High-performance liquid chromatographic assay of chloramphenicol in serum.

A new method for the analysis of serum chloramphenicol by reversed-phase, high-performance liquid chromatography (HPLC) is described. The method involves a preliminary extraction of 0.1 ml of serum with ethyl acetate containing an internal standard, chromatography with a reversed-phase C18 microparticulate column with an acetonitrile-acetate buffer mobile phase, and detection by measuring UV absorbance at 270 nm. Assay performance was compared with an existing microbiological assay. The HPLC method demonstrated both increased precision and increased sensitivity. The specificity of the HPLC method was also evaluated. The new method presents an alternative approach to the analysis of clinical specimens.

Chloramphenicol↗

Use of a PDP-12 computer for an on-line analysis of TC-chromatograms by a scanning system.

A software system, Chromscan, has been developed on a PDP-12 computer for quantitative analysis of TC-chromatograms and correlated problems in an on-line scanning system. The program controls a one- or two-dimensional scanning process of either a microscope stage or a modified TC-chromatogram photometer (Zeiss) storing the data on tape. The results can be obtained directly or in an off-line calculation by different Focal-12 programs. For spot evaluations a two-dimensional scan is performed with an aperture. The area of spots is measured and the integrated values of absorbed or remitted light represent the amount of separated substances. For line-scans slits are used. The pherogram is displayed on the scope to keep for baseline corrections peak-integration and some other handling under operators control.

Chromatography, Thin Layer↗

Decreases in protease nexins in Alzheimer's disease brain.

A marked and significant reduction of protease nexin-1 (PN-1) and PN-2/amyloid beta protein precursor (A beta PP) was observed in selected regions of Alzheimer's disease (AD) brains as compared to those of aged-matched controls. Correlative analysis indicated a relationship between PN-1 reduction and the severity of pathologic alterations. A statistically significant inverse correlation was noted between the level of PN-1 activity and the density of tau-positive dystrophic neurites in the hippocampus. In view of the ability of thrombin and PN-1 activity to regulate neurite outgrowth, it is possible that abnormal thrombin and PN-1 interactions may play a role in dystrophic neurite formation. The presence of clusters of dystrophic neurites around the capillaries suggests that blood-brain barrier (BBB) dysfunction may enhance such abnormal interactions. The decrease in PN-2/A beta PP levels in AD brains could possibly contribute to neuronal degeneration in AD in view of the ability of PN-2/A beta PP to protect neurons against the toxic effects of the A beta.

Aged↗