Endothelium-derived nitric oxide reduces baseline venous tone in awake instrumented rats.

To determine whether nitric oxide, which is likely endothelium-derived relaxing factor (EDRF), modulates baseline venous tone, the effects of intravenous NG-monomethyl-L-arginine (L-NMMA) (3-25 mg/kg), an EDRF inhibitor, on mean circulatory filling pressure (MCFP) were determined in 10 awake instrumented rats. MCFP, the equilibrated systemic pressure occurring when the circulation is arrested by transient inflation of a balloon in the right atrium, is a measure of total venous capacitance. L-NMMA caused a dose-dependent increase in mean arterial pressure and a dose-dependent decrease in heart rate. MCFP rose from 6.6 +/- 0.2 to 7.6 +/- 0.2 mmHg at the highest L-NMMA dose. The effects of L-NMMA on MCFP were reversed with L-arginine. In an additional four rats, in which hexamethonium was administered to induce ganglionic blockade, L-NMMA (25 mg/kg) caused a similar increase in MCFP (4.1 +/- 0.6 to 5.0 +/- 0.7 mmHg, P = 0.22) during the ganglionic blocked state as during the control unblocked state. These findings suggest that nitric oxide, which is likely EDRF, reduces baseline venous tone.

Aging increases venous compliance in awake instrumented rats.

To determine the effects of aging on total venous compliance, mean circulatory filling pressure (MCFP) was determined at several different blood volumes in 10 young (10-mo-old) and 10 older (30-mo-old) awake instrumented male Fischer 344/Brown Norway hybrid rats. Baseline weight and mean arterial pressure were similar in the two groups; heart rate was higher in the young (426 +/- 9 beats/min) than in the older rats (376 +/- 8 beats/min). Although MCFP was similar in the two groups at baseline blood volume, MCFP rose less with transient volume expansion and fell less with transient volume depletion in the older rats. The calculated venous compliance (reciprocal of the slope of the MCFP-to-volume relation) for the older rats was 25% greater than in the younger rats (3.28 +/- 0.21 vs. 2.63 +/- 0.12 ml.kg-1.mmHg-1; P = 0.014). In this conscious instrumented rat model, baseline total venous compliance is increased in older rats.

Case report: acyclovir neurotoxicity and nephrotoxicity--the role for hemodialysis.

Severe neurotoxicity and acute renal failure developed in a patient with newly diagnosed AIDS while receiving high-dosage intravenous acyclovir for disseminated herpes zoster. Hemodialysis resulted in a rapid resolution of neurologic symptoms and was associated with a reduction in plasma acyclovir concentration. Acute hemodialysis therapy should be considered in cases of serious neurotoxicity secondary to acyclovir, especially when accompanied by renal failure.

Adenosine increases total venous capacitance in awake instrumented rats.

To determine the effect of adenosine on the venous system, mean circulatory filling pressure (MCFP) was determined during infusion of intravenous (i.v.) adenosine (66.5 to a maximum of 532 microgram.kg-1.min-1) in 9 awake instrumented rats before and during ganglionic blockade with i.v. hexamethonium, 0.6 mg.kg-1.min-1. MCFP, the equilibrated pressure (mm Hg) occurring when the circulation is arrested by transient inflation of a balloon in the right atrium, is inversely related to total venous capacitance. Both adenosine and hexamethonium caused a reduction in mean arterial pressure (MAP); heart rate (HR) decreased during adenosine infusion in the blocked, but not the unblocked, state. In the unblocked state, baseline MCFP was 6.5 +/- 0.3 mmHg; hexamethonium caused baseline MCFP to decrease to 5.3 +/- 0.3 mm Hg. In both the unblocked and the blocked state, adenosine caused a dose-related decrease in MCFP [6.5 +/- 0.3 to 5.5 +/- 0.6 mm Hg (532 microgram.kg-1.min-1 adenosine dose) unblocked state; and 5.3 +/- 0.3 to 4.3 +/- 0.3 mm Hg (400 microgram.kg-1.min-1 adenosine dose) blocked state]. This decrease in MCFP induced by adenosine was highly significant. Intravenous adenosine, in an awake instrumented rat model, increases venous capacitance, with and without ganglionic blockade.

Stability of famotidine 20 and 40 mg/L and amino acids in total parenteral nutrient solutions.

The stability of famotidine in total parenteral nutrient (TPN) solutions and the concentrations of amino acids in the presence of famotidine were determined. Two famotidine concentrations (20 mg/L and 40 mg/L) and two amino acid concentrations (20 g/L and 42.5 g/L) were studied under the following storage conditions: refrigerated for 24 hours and then kept at room temperature (20-22 degrees C) for 24 hours, at room temperature for 48 hours, or refrigerated for seven days. Control TPN solutions were studied under the same storage conditions. TPN solutions also contained dextrose 25%, electrolytes, trace elements, and vitamins. Famotidine concentration was determined at 0, 24, and 48 hours and at seven days by high-performance liquid chromatography. Amino acid concentration was determined in the TPN solutions containing 42.5 g/L of amino acids without famotidine and with famotidine 40 mg/L under both 48-hour storage conditions. At 24 hours, all solutions retained at least 95% of the initial famotidine concentration. Seven of the eight famotidine solutions retained more than 95% of the initial famotidine concentration at 48 hours. All samples refrigerated for seven days retained more than 95% of the initial famotidine concentration. The concentration of amino acids in TPN solutions containing 42.5 g/L of amino acids was not affected by the addition of famotidine 40 mg/L under either 48-hour storage condition. Famotidine in concentrations of 20 mg/L and 40 mg/L is stable under the studied 48-hour storage conditions in TPN solutions containing amino acid concentrations of either 20 g/L or 42.5 g/L.(ABSTRACT TRUNCATED AT 250 WORDS)

Stability of famotidine 20 and 50 mg/L in total nutrient admixtures.

The stability of famotidine in total nutrient admixtures (TNAs) containing dextrose, an intravenous fat emulsion (IVF), and high or low concentrations of amino acids was studied. Famotidine was added to TNA solutions to final concentrations of 20 and 50 mg/L. TNA 1 contained 20% dextrose, IVF 40 g/L, and amino acids 42.5 g/L, and TNA 2 contained 25% dextrose, IVF 25 g/L, and amino acids 21.25 g/L. Control solutions of TNAs 1 and 2 without famotidine were also studied. All solutions were stored at 4 degrees C for 24 hours and then at 20-22 degrees C for 24 hours. The solutions were observed for signs of creaming or coalescence and measured for pH, famotidine concentration, and particle size at 0, 24, and 48 hours. No signs of creaming or coalescence were observed in control or test solutions throughout the study period. Famotidine in TNAs 1 and 2 showed a less than 5% change in concentration over the 48-hour period. Neither time nor amino acid concentration had any significant effect on famotidine concentration. Similarly, there were no significant differences in emulsion particle size between control solutions and TNAs containing famotidine and no significant changes in particle size over time. Famotidine 20 and 50 mg/L is stable in the TNAs tested when stored at 4 degrees C for 24 hours and then at 20-22 degrees C for 24 hours. Famotidine did not appear to disrupt the integrity of the emulsion system.

The stability of amikacin, gentamicin, and tobramycin in total nutrient admixtures.

Amikacin (A), gentamicin (G), and tobramycin (T) were added to eight different total nutrient admixtures (TNA) with varying concentrations of dextrose, amino acid, and fat emulsion to determine drug and emulsion stability. All TNA were prepared aseptically and stored at room temperature under normal room lighting for 12 hr before drug addition. One volume of each drug was added to an equal volume of each of the eight TNAs to simulate 1:1 piggyback contact volumes. Samples were left at room temperature for 6 hr. Drug concentrations were analyzed by fluorescence polarization immunoassay. TNA/drug admixtures were pH tested and visually inspected before and after centrifugation in microhematocrit tubes, noting signs of emulsion stability at 1 and 6 hr. Emulsion particle size was determined at 1 and 6 hr using interference contrast microscopy. All three drugs retained their immunoreactivity in all TNAs for at least 6 hr. G and T were stable in all eight TNAs for at least 6 hr with no significant effect on emulsion particle size or stability after centrifugation. A was incompatible with all eight TNAs, resulting in visual breaking of all emulsions within 1 hr. Therefore, G and T, but not A, can be administered via piggyback method with the eight TNAs tested if the infusion is completed within 6 hr.

Fourier transform atomic absorption flame spectrometry with continuum source excitation.

The design and performance of a Fourier transform atomic absorption flame spectrometer (FT-AAS) is presented. A 300-W xenon arc continuum source and a Michelson interferometer are used. A signal to noise disadvantage arising from the multiplex feature of FT-AAS is demonstrated by varying the photon flux at the detector without changing the exciting radiation. A grating is used for dispersion of the radiation before the interferometer to reduce the spectral window at the photomultiplier tube. Detection limits for several elements are generally an order of magnitude poorer than those obtained by continuum atomic absorption methods using echelle-grating spectrometers. Line profiles and absorption spectra, within the region of the spectral window selected by the grating, can be obtained with this method. Standard curves for sodium were constructed to extend the linear calibration range, by using absorbances measured at the absorption maximum and 0.022 nm off-line.

Unreliable visual estimation of the incidence and amount of turbidity, hemolysis, and icterus in serum from hospitalized patients.

We examined the frequency of occurrence for turbidity, hemolysis, or icterus in 2599 serum samples submitted for chemistry testing in an acute-care general hospital. Each specimen was compared visually with full-color photographs of adulterated serum, and designated as either "0" (containing no interferent), or trace, 1+, 2+, 3+, 4+, or 5+. Visible interferents (1+ or greater) were thought to be present in 838 (31%) of the specimens (icterus, 525; hemolysis, 244; lipemia, 69). To assess the accuracy of such visual grading, we determined the concentration of triglycerides, hemoglobin, or bilirubin in the specimens considered to be contaminated. There was little agreement between the actual concentration of each interferent and the assigned grade of turbidity, hemolysis, or icterus, confirming the unreliability of human visual estimation of these potentially interfering substances.

Stability of famotidine in minibags refrigerated and/or frozen.

The stability of famotidine 200 micrograms/ml in dextrose 5% injection (D5W) and in NaCl 0.9% (NS) solution in polyvinyl chloride (PVC) minibags was studied when these solutions were stored refrigerated at 4 degrees C for 14 days, or frozen at -20 degrees C for 28 days and then refrigerated for 14 days. Famotidine concentration was determined in the refrigerated samples immediately after compounding (time 0) and also on days 2, 4, 8, and 14 by high-performance liquid chromatography (HPLC). Famotidine concentration was determined by HPLC in frozen samples at time 0 and days 7, 14, 21, 28, 35, and 42. Solutions were also observed for visual changes and pH was tested at these time intervals. Results of the HPLC famotidine analysis demonstrated 94-107 percent recovery of famotidine in D5W and NS at 14 days in refrigerated samples and 98-100 percent recovery of famotidine in minibags frozen for 28 days then refrigerated for 14 days. Analysis of variance showed no time effect on the concentration of famotidine in refrigerated samples (p = 0.741). Linear regression of the frozen minibag data indicated no time effect. Famotidine 200 micrograms/ml is stable in dextrose 5% injection and NaCl 0.9% injection when stored in PVC bags at 4 degrees C for 14 days, or when frozen for 28 days and then subsequently refrigerated for 14 days.

Effect of storage temperature and shaking rate on pH and blood-gas results for two quality-control products.

Directions for pre-analytical handling of ampules of two commercially available aqueous quality-control products (contrlL and G.A.S.) contain vague instructions such as "store at room temperature" and "shake vigorously" before analysis. We examined the effect of different storage temperatures (25, 31, and 38 degrees C) and shaking rate (one, two, and four shakes per second) on pH and blood-gas results. For both products, increasing the storage temperature significantly decreased pO2 results, the magnitude of the bias being greatest for those solutions with the highest O2 tensions. However, increasing the shaking rate partly offset this bias. Increasing storage temperature also decreased results for pCO2 and increased results for pH for both manufacturers' ampules with the highest CO2 tensions, and this bias was not offset by increasing the shaking rate. We conclude that both storage temperature and shaking rate must be precisely defined and carefully monitored before these products are used in a quality-control program.

Analytical systems ranked by freedom from interferences.

We determined the effect of hemolysis, lipemia, and bilirubinemia on clinical-chemical analytical results under standardized conditions, for serum specimens prepared by us. Our purpose was to assess results obtained with 22 commonly available analytical systems. The quantitative rating scheme described is derived from the observed interference(s) divided by the number of analytical methods evaluated. The combined ranking reveals which chemistry analyzers are least affected and which are most affected by the added substances. Generally, systems that incorporate physical barriers or protein-separation steps perform better than those without thin-film layers, glass-fiber barriers, or dialysis membranes. Among the "direct" analyzers, fewer interferences are seen if appropriate "blanking" wavelengths are used, especially if a "specimen blank" absorbance is used appropriately in the analytical system. Centrifugal analyzers tended to perform poorly, according to the criteria presented here.

The effect of thioridazine on the Automatic Clinical Analyzer serum tricyclic anti-depressant screen.

A patient who had ingested thioridazine and flurazepam was brought to the authors' emergency department. Initial laboratory evaluation included a positive result for a serum screening test for tricyclic anti-depressants performed with the DuPont Automatic Clinical Analyzer. This false positive test result caused considerable unnecessary treatment and expense for the patient. The authors have found that a serum thioridazine concentration of 125 ng/mL (within the usual therapeutic range for this drug) will produce a false positive automatic clinical analyzer serum tricyclic anti-depressant screen result. Because thioridazine is the most widely used phenothiazine and is prescribed more frequently than the most widely used tricyclic anti-depressant, it is important to recognize this cause of a false positive result.

Emergency screening for ethylene glycol in serum.

We have exploited the "interference" of ethylene glycol in the Du Pont aca triglyceride method to develop a convenient and rapid screening method for detecting ethylene glycol in serum. Pretreatment of patient's serum with lipase, glycerol kinase, and other cofactors usually added for triglyceride analysis removes triglycerides and glycerol, but not ethylene glycol, from the sample. The aca triglyceride method may then be used to estimate the ethylene glycol concentration in serum.