Determination of urinary 3-methoxy-4-hydroxymandelic and 3-methoxy-4-hydroxyphenylacetic acids by fused silica capillary gas chromatography.
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Biomedical subjects
Publications and source records attributed to J D Berg.
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We describe a new approach to the bentiromide test of exocrine pancreatic function, p-Aminosalicylic acid (PAS), a compound closely related to the bentiromide fragment p-aminobenzoic acid (PABA), is used as a marker of the pharmacokinetic behavior of PABA to derive a PABA excretion index. This index is identical to that derived with [14C]-PABA. Concentrations of both PABA and PAS are measured in urine by "high-performance" liquid chromatography, which avoids the drug interferences encountered with established assays of PABA. We discuss the practical and diagnostic advantages of this new approach to the bentiromide test.
The resistance of bacteria to antimicrobial agents could be influenced by growth environment. The susceptibility of two enteric bacteria, Yersinia enterocolitica and Klebsiella pneumoniae, to chlorine dioxide was investigated. These organisms were grown in a defined medium in a chemostat and the influence of growth rate, temperature, and cell density on the susceptibility was studied. All inactivation experiments were conducted with a dose of 0.25 mg of chlorine dioxide per liter in phosphate-buffered saline at pH 7.0 and 23 degrees C. The results indicated that populations grown under conditions that more closely approximate natural aquatic environments, e.g., low temperatures and growth at submaximal rates caused by nutrient limitation, were most resistant. The conclusion from this study is that antecedent growth conditions have a profound effect on the susceptibility of bacteria to disinfectants, and it is more appropriate to use the chemostat-grown bacteria as test organisms to evaluate the efficacy of a certain disinfectant.
A method was developed to grow Legionella pneumophila in continuous culture. A chemostat was used to simulate nutrient-limited, submaximal growth in the natural environmental and to provide a precisely controlled growth regimen. Cultures grew under forced aeration under conditions yielding up to 38% saturation of dissolved oxygen; supplemental CO2 (5%) at the same gas flow rates as ambient air had no effect on culture growth. Pleomorphism was observed during growth under all conditions. Pigment was produced only at D less than 0.03 h-1. Catalase was produced at higher growth rates but not at higher temperatures. The pathogenicity was unaffected by altering either the growth rate or the growth temperature.
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A practical method for determining p-aminobenzoic acid in urine by high-performance liquid chromatography has been assessed. The technique is quick, requires no extraction steps and has good precision. Using this method, healthy individuals had a p-aminobenzoic acid excretion index of 94% +/- 18 (mean +/- 1 SD). Patients with proven, severe chronic exocrine pancreatic dysfunction had index values of less than 5-25%. Unlike chemical methods available, there were no interferences in any of the urines tested, nor did 12 compounds tested interfere with the analysis.
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Serum bile acid levels in 61 patients receiving daily doses of rifampicin and isoniazid for the treatment of tuberculosis have been investigated. Bile acids were measured using 3 alpha-hydroxysteroid dehydrogenase in a continuous-flow system. Abnormally elevated levels were found in 44 patients (72%) during the period of study up to 80 days after onset of treatment. The results showed a mean of 24.9 mumol/l and a positively skewed distribution. Whilst marginally raised levels of bilirubin were seen in some samples (mean 8.2 mumol/l), these did not reflect the marked changes observed in bile acids. Patients receiving rifampicin and isoniazid may therefore have markedly elevated levels of total serum bile acids, while other tests used to assess liver function can remain normal.
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Bacterial resistance to inactivation by antibacterial agents that is induced by the growth environment was studied. Escherichia coli was grown in batch culture and in a chemostat, and the following parameters were varied: type of substrate, growth rate, temperature, and cell density during growth. Low doses (0.75 mg/liter) of chlorine dioxide were used to inactivate the cultures. The results demonstrated that populations grown under conditions that more closely approximated natural aquatic environments were more resistant than those grown under commonly employed batch culture conditions. In particular, bacteria grown at submaximal rates were more resistant than their counterparts grown at mumax. The most resistant populations encountered in this study were those grown at D values of 0.02 h-1 and 0.06 h-1 at 25 degrees C. Growth at 15 degrees C led to greater resistance than did growth at 37 degrees C. The conditions that produced relatively resistant phenotypes were much closer to those found in most natural environments than are the typical conditions of batch culture methods. The importance of major physiological changes that can be induced by the antecedent growth environment is discussed in light of the possible modes of action of several disinfectants.
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Evidence of delayed progression is the primary mechanism for demonstrating therapeutic efficacy in clinical trials in Alzheimer's disease. In the major trials of therapeutic treatment of AD, to date, measures based on clinical judgement and cognitive performance, instead of mortality, have been used as the primary response measures. There is good reason for this since the course of the disease is quite long, and AD trials designed around mortality would require either very large sample sizes or very long follow-up in order to have adequate power. However, the evaluation of progression in AD using clinical markers is subject to a number of challenges often found in longitudinal databases, for example, missing data, floor and ceiling effects and non-linearity. Unfortunately, few of these issues are being addressed in the typical analysis of progression data. This paper explores these analytic issues in the context of the recently completed Alzheimer's Disease Cooperative Study trial of vitamin E and Selegeline in moderate AD patients.