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Biomedical subjects

W Blackwell

Publications and source records attributed to W Blackwell.

15 recordsLinked to original sources

Butoxyethanol ingestion with prolonged hyperchloremic metabolic acidosis treated with ethanol therapy.

BACKGROUND: Severe toxic ingestions of butoxyethanol (CAS No. 111-76-2) are rare despite the prevalence of this glycol ether in products such as glass and surface cleaners. Manifestations of acute butoxyethanol toxicity include metabolic acidosis, hemolysis, hepatorenal dysfunction, and coma, but vary widely in reported cases. Furthermore, the optimal therapeutic approach is not yet established. Much of the toxicity of butoxyethanol has been ascribed to its aldehyde and acid metabolites which are similar to those produced by oxidative metabolism of methanol and ethylene glycol. Although the roles of alcohol dehydrogenase inhibition with ethanol or fomepizole and hemodialysis are clear in the case of toxic ingestions of methanol and ethylene glycol, they remain poorly defined for butoxyethanol poisoning. CASE REPORT: We report the case of a 51-year-old female who ingested up to 8 ounces of Sanford Expo White Board Cleaner (butoxyethanol and isopropanol). She developed prolonged hyperchloremic metabolic acidosis and mental status depression and was treated with ethanol therapy but not hemodialysis. This patient recovered without apparent sequelae. The kinetics of butoxyethanol metabolism in this case are described and the potential therapeutic options are discussed.

Acidosis↗

Folate and vitamin B12 status of adolescent girls in northern Nigeria.

The diets of populations in many developing countries are low in folate and vitamin B12 and a deficiency of either of these vitamins results in increased risk for cardiovascular disease and neural tube defects. The rates of neural tube defects in Nigeria are among the highest reported worldwide. Since many girls marry at an early age in northern Nigeria, we therefore determined the folate and vitamin B12 status of adolescent girls between 12 and 16 years of age in Maiduguri, Nigeria. The mean serum folate concentration for subjects was 15.3 +/- 5.2 nmol/L. Whereas only four subjects (2.4%) had serum folate concentrations lower than 6.8 nmol/L, a level indicative of negative folate balance, 9% of the subjects had serum vitamin B12 concentrations at or below 134 pmol/L, the lower limit of the reference range for their age group. Serum homocysteine was measured in 56 of the 162 subjects and the mean level was 15.9 +/- 5.0 mumol/L. The majority of subjects had serum homocysteine concentrations above the upper limit of the reference range for their age group. We conclude that the adolescent girls we studied were at greater risk for vitamin B12 deficiency than folate deficiency. This conclusion is consistent with the fact that their diet included few foods that contained vitamin B12.

Adolescent↗

Use of the Trolox assay to estimate the antioxidant content of seventeen edible wild plants of Niger.

Although wild edible plants of the western Sahel and other parts of sub-Saharan Africa are consumed to some extent at all times of the year, greater amounts are consumed when cereal harvests are insufficient to support the populations living in these areas. The purpose of this study was to use a recently reported Trolox-based assay to measure the total antioxidant capacity of aqueous extracts of 17 plants that we gathered from southern Niger. The antioxidant contents of the aqueous extracts were compared to those of spinach and potato. Of the 17 plants, 11 had a greater antioxidant content than spinach and 14 had a greater antioxidant content than potato. The leaves of Tapinanthus globiferus had the greatest antioxidant content, and the fruit of Parinari macrophylla had the lowest. In general, leaves contained more antioxidants than either fruits or seeds. The total antioxidant capacity of the aqueous extracts was relatively high, indicating that the wild plants of the western Sahel may contain substantial amounts of water-soluble flavonoid glycosides, which are potent antioxidants and have been shown to have anticancer properties.

Antioxidants↗

Rapid automated determination of lipid hydroperoxide concentrations and total antioxidant status of serum samples from patients infected with HIV: elevated lipid hydroperoxide concentrations and depleted total antioxidant capacity of serum samples.

Excessive production of oxygen free radicals causes the oxidation of circulating or membrane lipids, proteins, and DNA. Patients infected with HIV usually have severe malnutrition in the AIDS stage of disease. Therefore, they may be at higher risk of oxidative stress. We measured lipid hydroperoxide concentration, antioxidant status, cholesterol, triglyceride, iron, ceruloplasmin, and transferrin concentrations in the serum samples of 14 patients infected with HIV and compared our results with the results from 14 volunteers who served as controls. Lipid hydroperoxide concentrations in serum samples were measured by a colorimetric assay in which hemoglobin catalyzes the reaction of lipid hydroperoxide with a methylene blue derivative, yielding methylene blue. The total antioxidant capacity of serum was measured by the ability of serum to inhibit the formation of ferrylmyoglobin by metmyoglobin and hydrogen peroxide. Both assays were automated on the Syva-30R analyzer (Behring, San Francisco, Calif). We measured serum cholesterol and triglyceride concentrations by using the Vitro 950 analyzer (Johnson & Johnson, Rochester, NY). The lipid hydroperoxide concentrations were significantly elevated (mean, 1.44; SD, 0.95 micromol/L) in patients with HIV compared with control subjects (mean, 0.25; SD, 0.24 micromol/L). In contrast, the total antioxidant capacity was significantly lower in patients with HIV (mean, 1.04; SD, 0.13 mmol/L of trolox equivalent) compared with control subjects (mean, 1.66; SD, 0.09 mmol/L). We observed a fair correlation between serum lipid hydroperoxide concentrations and serum triglyceride concentrations in patients with AIDS. The correlation between serum hydroperoxide concentration and antioxidant status of serum was relatively poor. The lipid hydroperoxide assay was linear, from 0.1 micromol/L to 50 micromol/L. The within-run and between-run coefficients of variation were 3.5% and 4.5%, respectively, at a lipid hydroperoxide concentration of 2.5 micromol/L. The total antioxidant capacity assay was linear, from 0.1 to 2.5 mmol/L of trolox equivalent. The within-run and between-run coefficients of variation were 1.4% and 4.2% for the standard, with a target total antioxidant capacity of 1.5 mmol/L of trolox equivalent. We conclude that our automated assays for determination of total antioxidant status of serum and lipid hydroperoxide products may be helpful screening tests followed by measuring individual antioxidants, such as tocopherol, ascorbic acid, and other antioxidants for patients with severe deficiency of antioxidant status.

Antioxidants↗

Gas chromatography-electron ionization and chemical ionization mass spectrometric analysis of urinary phenmetrazine after derivatization with 4-carbethoxyhexafluorobutyryl chloride--a new derivative.

Phenmetrazine is a central nervous system stimulant currently used as an anorectic agent. The drug is abused and is reported to cause death from overdose. We describe a new derivatization method for phenmetrazine using 4-carbethoxyhexafluorobutyryl chloride. Quantitation of urinary phenmetrazine can be easily achieved by using N-ethyl amphetamine as an internal standard. The electron ionization mass spectrum of 4-carbethoxyhexafluorobutyryl derivative of phenmetrazine showed a molecular ion at m/z 427 and a base peak at m/z 70. In the methane chemical ionization mass spectrum, the base peak was observed at m/z 428 (protonated molecular ion). In the electron ionization mass spectrum of 4-carbethoxyhexafluorobutyryl derivative of the internal standard, N-ethyl amphetamine we did not observe a molecular ion. However, in the chemical ionization mass spectrum, the protonated molecular ion at m/z 414 was the base peak. The retention time of derivatized phenmetrazine (8.4 min) was substantially longer than the retention time of the underivatized molecule. Moreover, underivatized phenmetrazine showed poor peak shape (substantial tailing) while derivatized phenmetrazine had excellent chromatographic properties. The within-run and between-run precisions of the assay were 2.6% and 3.1% respectively at a urinary phenmetrazine concentration of 10 micrograms/mL. The assay was linear for urinary phenmetrazine concentration of 1 to 100 micrograms/mL with a detection limit of 0.2 microgram/mL.

Amphetamines↗

Gas chromatographic-mass spectrometric identification and quantitation of urinary phenols after derivatization with 4-carbethoxyhexafluorobutyryl chloride, a novel derivative.

Urinary phenol is analyzed widely to determine benzene exposure in humans. Most methods utilize direct measurements of phenols after extraction from urine using gas chromatography or high-performance liquid chromatography. We describe a novel derivatization of urinary phenols using 4-carbethoxyhexafluorobutyryl chloride after extraction from urine and subsequent analysis by gas chromatography-mass spectrometry. The derivative elutes at significantly higher temperature than phenol and the method is free from interferences from more volatile components in urine. We also observed excellent chromatographic properties of these derivatives. In addition, we observed strong molecular ions for the 4-carbethoxyhexafluorobutyryl derivative of phenol (m/z 344), p-cresol (m/z 358) and the internal standard 3,4-dimethylphenol (m/z 372) and other characteristic ions in the electron ionization, thus aiding in unambiguous identification of these compounds. The protonated molecular ions (m/z 373 for derivatized phenol, m/z 359 for derivatized p-cresol and m/z 373 for the internal standard) were the base peaks (relative abundance 100%) in the chemical ionization, although other secondary peaks were less abundant. The assay is linear for phenol concentration of 1-100 mg/l. The within-run and between-run precisions were 4.8% (mean = 52.4, S.D. = 2.5 mg/l) and 8.1% (mean = 53.0, S.D. = 4.3 mg/l) respectively, and the detection limit was 0.5 mg/l.

Acids↗

Decreased total antioxidant capacity but normal lipid hydroperoxide concentrations in sera of critically ill patients.

Oxidative stress (when free radical generation exceeds antioxidant defense) occurs in many human diseases and makes significant contributions to their pathogenesis. We automated assays estimating the antioxidant status of serum, and lipid hydroperoxide concentrations using the Monarch analyzer. In this assay, the antioxidant status of serum is measured by its ability to inhibit generation of free radicals from 2,2'-amino-di-[3-ethylbenzthiazole sulphonate] by metmyoglobin and hydrogen peroxide. The assay for measuring lipid peroxidation products in serum utilizes the ability of lipid hydroperoxides to generate methylene blue from 10N-methylcarbamyl 3,7-dimethylamino 10H-phenothiazine. We detected no lipid hydroperoxide in sera obtained from 24 controls. The mean antioxidant status was 1.69 mmol/l (SD; 0.20 mmol/l) in controls. The antioxidant capacity of serum was significantly reduced in sera of critically ill patients in the medical intensive care unit (mean = 1.05, SD = 0.26 mmol/l) with p value less than 0.05 by independent t-test, two tailed. Lipid peroxidation products were not significantly elevated in critically ill patients, however lipid peroxidation products were significantly elevated in hemodialysis patients (mean = 1.40, SD = 0.47 mumol/l) and in some kidney transplant recipients. We conclude that antioxidant capacity of sera in critically ill patients is significantly reduced.

Antioxidants↗

A rapid cost-effective high-performance liquid chromatographic (HPLC) assay of serum lamotrigine after liquid-liquid extraction and using HPLC conditions routinely used for analysis of barbiturates.

Lamotrigine (lamictal) is a new anticonvulsant drug approved by the FDA for clinical use. Therapeutic monitoring of lamotrigine is useful for patient management and avoidance of toxicity. The suggested therapeutic range is 1 to 4 micrograms/ml. The authors describe a simple high-performance liquid chromatographic (HPLC) method for analysis of lamotrigine from serum. Serum (0.5 ml) was alkalinized with borate buffer (pH 9.8). Lamotrigine and the internal standard thiopental were extracted with 10 ml of chloroform. After evaporation of the extract, the residue was reconstituted in the mobile phase (prepared by mixing 750 ml of potassium dihydrogen phosphate, 550 ml of deionized water, 430 ml of methanol, and 100 microliters of triethylamine as an ion pairing reagent) and injected into an LC-18 column (15 cm x 4.6 mm). The authors use this HPLC system routinely in their laboratory for the analysis of barbiturates. They demonstrated that the same system can be used for the analysis of lamotrigine. The within-run and between-run precisions of the lamotrigine assay were 1.63% (mean = 3.05, SD = 0.05 microgram/ml, n = 6) and 3.7% (mean = 2.97 micrograms/ml, SD = 0.11, n = 8). The assay was linear for serum lamotrigine concentrations of 0.5 microgram/ml to 20 micrograms/ml with a detection limit of 0.5 microgram/ml. The authors observed excellent correlation between serum lamotrigine concentrations measured by their assay and a reference laboratory in six patients receiving lamotrigine. Their assay is free from interferences from common tricyclic antidepressants, benzodiazepines, other common anticonvulsants, salicylate, and acetaminophen.

Anticonvulsants↗

Stability of therapeutic drug measurement in specimens collected in VACUTAINER plastic blood-collection tubes.

Recently Becton-Dickinson marketed a plastic serum-separator tube that uses the same serum-separator gel as the glass tubes. We studied the stability of therapeutic drugs stored in plastic tubes by comparing it with the stability of drugs stored in glass serum-separator tubes and plain red-top glass tubes. We observed no absorption of caffeine, primidone, N-acetylprocainamide, procainamide, theophylline, tobramycin, ethosuximide, acetaminophen, amikacin, valproic acid, methotrexate, salicylate, and cyclosporine in either plastic or glass serum-separator tubes. On the other hand, concentrations of lidocaine, quinidine, phenobarbital, and phenytoin were reduced after storing in both plastic and glass serum-separator tubes, especially with prolonged storage and small sample volume. The reduction in concentrations were due to slow absorption of those drugs by serum-separator gel.

Blood Specimen Collection↗

Gas chromatographic-mass spectrometric identification and quantitation of ethylene glycol in serum after derivatization with perfluorooctanoyl chloride: a novel derivative.

Ethylene glycol poisoning is a common clinical problem and identification as well as quantitation of ethylene glycol in serum is important for medical and legal purposes. Most investigators described determination of ethylene glycol by gas chromatography without derivatization or derivatives forming a molecular ion < 200. We describe a novel derivatization technique of ethylene glycol using perfluorooctanoyl chloride, after extraction from serum using acetone. This derivative has a molecular mass of 854 and produces a base peak at m/z 441 and other diagnostic strong peaks for unambiguous identification. Moreover, this derivative is less volatile and is free from interferences from endogenous serum components. Quantitation can be achieved by using 1,4-butanediol as an internal standard. The assay showed within-run and between-run precision of 7.2% and 8.0%, respectively, and linearity over the serum ethylene glycol concentration range 70-2240 micrograms/ml with a detection limit of 5 micrograms/ml.

Caprylates↗

Adsorption of charged non-albumin bound drugs by amorphous silica.

We investigated the in vitro drug adsorption of PQ 10150 sodium silicate gel (AIS, Santa Clara, CA) with particle size of 230 microns and surface area of 400 m2/g. We observed 99% to 88% adsorption of gentamicin; a mean 91% of disopyramide; a mean 89% of quinidine at low concentration, falling to 75% at higher concentration. Insulin was 88% adsorbed at low concentrations but less so (65%) at higher concentrations. We observed a mean 83% adsorption of procainamide, a mean 84% of N-acetyl procainamide, 74% of lidocaine, 73% of amitriptyline, and 44% of desipramine. We found an average of 14% reduction of total digoxin concentration when serum containing digoxin (2 to 33 ng/mL) was exposed to sodium silicate, while the reduction in free digoxin concentration was 16%. Five percent ethosuximide was also removed. The adsorption of theophylline, phenobarbital, acetaminophen, phenytoin, ethylene glycol, methotrexate, salicylate, thiocyanate and diazepam was minimal and not significant. We conclude that significant amounts of charged, non-albumin bound drugs can be removed by PQ 10150 sodium silicate gel.

Adsorption↗

Enzymatic method for measuring ethylene glycol with a centrifugal analyzer.

We describe a semiautomated, enzymatic method of analysis for ethylene glycol in plasma. Glycerol dehydrogenase (EC 1.1.1.6) from Enterobacter aerogenes, which has high specificity for ethylene glycol, is mixed with 3 microL of specimen in a centrifugal analyzer. NAD+ is added to initiate the reaction, and 450 s after an initial 90-s delay, the absorbance at 340 nm is measured. Monthly calibration with a five-point calibration curve is sufficient to provide between-day precision (CV) of 2% to 5%. The detection limit is 0.3 mmol/L with a CV of 10%. There is no significant interference from ethanol, methanol, isopropanol, acetone, lactate, or glycerol.

Centrifugation↗

Sarcoplasmic reticulum dysfunction: phospholipid alterations induced by lysosomal phospholipase C.

Previous work has demonstrated that myocardial ischemia results in a breakdown of the excitation-contraction coupling system of cardiac muscle associated with lysosomal activation. It has been hypothesized that lysosomal activation during the course of myocardial ischemia is mediated by the production of oxygen free radicals. We have tested the hypothesis that myocardial ischemia results in the activation of lysosomal phospholipase C and disruption of calcium transport in sarcoplasmic reticulum (SR) mediated by oxygen free radicals. Three groups of dogs were studied: sham-operated controls (n = 6); normothermic global ischemia of 30-min duration (n = 6); and 30 min of normothermic global ischemia pretreated with intracoronary superoxide dismutase (SOD, 10 micrograms/ml) plus catalase (25 micrograms/ml). In vitro, isolated SR demonstrated a significant depression of calcium uptake rates and Ca2+-stimulated, Mg2+-dependent ATPase activity at both pH 7.0 and 6.4 with the depression at pH 6.4 greater than 7.0. This depression of SR function was significantly inhibited in hearts pretreated with SOD plus catalase. In sham-operated controls, acid-induced dysfunction was associated with substantial loss of phospholipid phosphorus and major changes in phospholipid composition. SR contained an extremely active, ion-independent sphingomyelinase-phospholipase C (SM-PLC) that had maximal activity at pH 4.5-5.0. This SM-PLC was activated when control SR was incubated at acid pH and the specific activity of SM-PLC was decreased 50% in SR isolated from normothermic global ischemia. Activity remained at control levels in hearts pretreated with SOD plus catalase.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗