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Biomedical subjects

B Law

Publications and source records attributed to B Law.

At least 19 recordsLinked to original sources

Fundamental studies in reversed-phase liquid-solid extraction of basic drugs; III: Sample matrix effects.

Using a set of 13 basic solutes (including a quarternary ammonium compound) with controlled pKa, log P and plasma protein binding, the factors which influence the extraction of these compounds from plasma by reversed-phase liquid-solid extraction have been studied. Direct analysis of plasma, avoiding deproteination, etc., is possible providing the sample is applied to the cartridge under the appropriate conditions. These conditions are dictated by the degree of plasma protein binding and are controlled and predicted from the lipophilicity of the compound. Plasma samples containing lipophilic compounds (log D(pH 7.4) > 2.03) require acidification and samples containing more polar compounds (log D(pH 7.4) < 0.9) should be applied untreated. Failure to use the appropriate conditions can result in significant losses from the cartridge on application or washing. In the intermediate lipophilicity range the optimal application conditions cannot be predicted. The effect of various aqueous-organic wash solvents have been investigated, and it was found that the cationic but not the proteinaceous components of plasma also affect the extraction process. This phenomenon which is probably due to an attenuation of the secondary cation exchange mechanism, results in more facile elution than when compounds are applied in water.

Atenolol

Demonstration of the compatibility of narrow-bore packed column high-performance liquid chromatography with conventional detection systems.

A number of commercially available high-performance liquid chromatography detectors fitted with conventionally sized flow cells (4.5 to 14 microliters) have been evaluated for use for narrow-bore (1-3 mm i.d.) packed columns. Contrary to the popular misconception, small flow cell volume (and consequently short path length) does not appear to be a prerequisite for successful use of narrow-bore columns. The 1 mm i.d. columns when used with certain detectors gave up to a 17-fold increase in sensitivity, compared with conventional 4.6 mm i.d. columns. This work, which was carried out using conventional injection volumes (50 microliters), shows that narrow-bore HPLC columns can be used in most laboratories to significant advantage without costly conversion of existing equipment.

Chromatography, High Pressure Liquid

A case of insect borne tularemia above the tree line.

A case of insect borne transmission of ulceroglandular tularemia in Canada above the tree line is presented. It seems likely from the available entomological data that a mosquito was the vector in this case. Mosquito vectors may be important in inducing the high seroprevalence of antibodies to F. tularensis above the treeline. This case is presented to make clinicians aware of the possibility of tularemia in cases of insect borne ulceroglandular disease in the arctic and, the necessity of measuring tularemia agglutinins in these patients. It should be noted that isolation of this organism poses a risk to laboratory personnel, and therefore should only be attempted in a reference laboratory. Therefore the diagnosis is based upon the finding, in the appropriate clinical context, of a four-fold rise in the tularemia agglutinins, or a single convalescent titre of 1:160 or greater.

Adolescent

An outbreak of methicillin-resistant Staphylococcus aureus in a pediatric hospital--how it got away and how we caught it.

An outbreak of methicillin-resistant Staphylococcus aureus (MRSA) occurred in a hospital without endemic MRSA, following the transfer of a patient colonized by MRSA from another hospital known to have a problem with endemic MRSA. Despite initial appropriate isolation and therapy to eradicate colonization of the organism, the index child relapsed 10 weeks after the last prior positive culture. Simultaneously, the organism was isolated from two other patients on the same ward, and subsequently at surgery from one child transferred to the neonatal intensive care nursery. Antimicrobial therapy for urinary tract infection likely impaired earlier identification of MRSA in the index case. Suppression with mupirocin rather than eradication may have resulted in inappropriate early discontinuation of infection control precautions. Control of the outbreak and eradication of the organism from all patients was successful after intensive surveillance and control measures, including strict isolation and cohorting. This outbreak suggests that infection control precautions and intensive screening of contacts, as well as positive cases, may be effective for control and eradication of MRSA from health care facilities with recent introduction of an epidemic strain.

Child, Preschool

Chromatographic retention relationships between aliphatic tertiary amines and their putative N-oxide metabolites--preliminary results.

The chromatography of a series of tertiary amines and the corresponding N-oxides have been studied and the Functional Group Contribution Approach used to describe retention correlations between them. Good correlations are observed between the behaviour of compounds on HPLC and with the exception of some alicyclic nitrogen compounds also on thin layer chromatography. The models produced are used to predict k' and Rf values for ranitidine N-oxide and tamoxifen N-oxide based upon those for the parent molecule. The deviation between actual and predicted values was larger than expected, presumably due to the structural or physico-chemical differences of ranitidine and tamoxifen compared to the model compounds.

Amines

Group A streptococcal pharyngeal carriage, pharyngitis, and impetigo in two northern Canadian native communities.

The prevalence of pharyngeal carriage of group A streptococci, streptococcal pharyngitis, and impetigo was determined in schoolchildren in two northern communities, one Inuit (mean number of schoolchildren surveyed, 233) and one native Indian (mean number of schoolchildren surveyed, 349). At three surveys from November 1984 to May 1985, pharyngeal group A streptococcal carriage was 5.3%, 22%, and 34% in the Inuit community and 5.3%, 5.1% and 10% in the native Indian, with impetigo prevalence 1.6%, 3.8% and 1.0%, and 2.4%, 4.2% and 0.6%, respectively. Increased pharyngeal carriage correlated with the increasing number of household residents and the lower school grade. In 12 months of observation the incidence of group A streptococcal pharyngitis was 49/100 schoolchildren for the Inuit and 9.4/100 for the native Indian community, with impetigo 13/100 and 11/100 respectively. The maximal incidence of pharyngitis was late winter in the Inuit community and midsummer in the native Indian. The incidence of impetigo peaked in January for both communities. M and T typing showed consecutive outbreaks of different serotypes in the Inuit community, but a persistent low level of endemic infection in the Indian community. These observations suggest a seasonal prevalence of group A streptococcal pharyngeal carriage consistent with other North American populations, but marked inter-community variation in pharyngeal carriage and disease. The midwinter peak of impetigo appears unique to these populations.

Adolescent

Short-course antibiotic therapy for urinary tract infections in children. A methodological review of the literature.

We performed a methodological review of 14 published clinical trials of short-course (less than or equal to 4 days) vs conventional (seven to ten days) antibiotic therapy for urinary tract infection in children. Four reviewers independently assessed each study, without knowledge of authorship, according to 35 criteria, 14 of which were considered critical for this type of study. Reviewer ratings were summed so that any study could receive a potential score of 140 for all criteria and 56 for the critical criteria. Only one study met more than 75% of all the criteria, whereas four studies met 75% of critical criteria. Two studies found short-course antibiotic therapy significantly less effective than conventional therapy. The remaining 12 had insufficient sample size to warrant the conclusion that the two therapies were equivalent. We conclude that there is insufficient evidence to warrant the use of short-course antibiotic therapy for urinary tract infection in children and that a much larger study, with attention to some of the details described, is warranted.

Anti-Bacterial Agents

Analysis of basic compounds on a silica column with an aqueous methanol eluent. The use of quantitative structure-retention relationships in metabolite identification.

High-performance liquid chromatography data for 69 mono-functional aryl-alkyl amines was generated using a silica column and an aqueous methanol eluent (pH 9.1). Retention was shown to be due to a cation-exchange mechanism and was controlled by the solute pKa and the degree and type of substitution at or near the basic centre. The effect of various substituents--some common to metabolic transformation--could be quantified using the group contribution values (tau). The study was extended to include a further 32 compounds representative of five diverse drug classes. The group contribution data for these drugs and metabolites were similar to those for the model compounds. A number of common biotransformations were well characterised, including N-desmethylation, N,N-didesmethylation and ring hydroxylation. The data demonstrates how the group contribution values can be used to help elucidate the identity of a metabolite from chromatographic data.

Alkalies

Comparison of nasopharyngeal aspirate and nasopharyngeal swab specimens for respiratory syncytial virus diagnosis by cell culture, indirect immunofluorescence assay, and enzyme-linked immunosorbent assay.

Paired nasopharyngeal aspirate (NPA) and nasopharyngeal swab (NPS) specimens obtained from each of 32 hospitalized infants with X-ray-confirmed pneumonia (91%) or bronchiolitis were tested for respiratory syncytial virus (RSV) infection by virus culture, the indirect immunofluorescent-antibody (IFA) technique, enzyme-linked immunosorbent assay (ELISA; Ortho Diagnostic Systems, Inc.), and spot hybridization with a human genomic probe to quantitate cellular DNA. RSV was isolated in cell cultures from 72% (23 of 32) of patients by using NPA specimens compared with 47% (15 of 32) by using NPS specimens. With tissue culture positivity as the reference test, the sensitivities of the ELISA on NPA and NPS specimens were found to be 69% (16 of 23) and 61% (14 of 23), respectively, with a specificity and a positive predictive value from both sites of 100%. The sensitivities of the IFA technique compared with the cell culture on NPA and NPS specimens were 61% (14 of 23) and 52% (12 of 23) with specificities of 89 and 78% and positive predictive values of 96 and 92%, respectively. Despite the recovery of significantly more cells (as shown by detection of more cellular DNA by using NPA specimens), virus was detected by the IFA technique or ELISA at similar frequencies in paired specimens. However, virus was recovered more often from NPA than NPS specimens by cell culture, and ELISA optical density readings and the number of RSV-positive fluorescing cells were greater for NPA specimens. NPA specimen collection was less traumatic for the patient, was an easier procedure for the physician to perform, and provided a superior laboratory specimen for RSV diagnosis than the NPS technique.

Animals

High-performance liquid chromatography systems for the separation of benzodiazepines and their metabolites.

The high-performance liquid chromatographic (HPLC) retention characteristics of 21 benzodiazepine drugs and some of their metabolites have been examined on both silica and ODS-silica packing materials. Four HPLC systems have been considered and retention data are presented for the drugs on these systems. The correlation of retention data on the systems is considered with reference to the problem of identifying unknown benzodiazepines.

Anti-Anxiety Agents

Appraisal of narrow-bore (1 mm I.D.) high-performance liquid chromatography columns with view to the requirements of routine drug analysis.

The potential advantages of using 1-mm bore high-performance liquid chromatography columns to replace conventional 4-5-mm bore columns for routine drug analysis have been considered in the light of various claims and counter-claims in the scientific literature. Experimental work has been conducted to measure the changes in mass sensitivity when using both UV and electrochemical detection. Further work has investigated the coupling of these narrow-bore columns in order to achieve high plate counts with particular reference to the influence of peak asymmetry. Finally the linking of the narrow-bore columns to a mass spectrometer with a moving-belt interface has been examined. All results are discussed with reference to the needs of the routine analyst.

Chromatography, High Pressure Liquid