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Biomedical subjects

S Bolton

Publications and source records attributed to S Bolton.

At least 37 records · Page 2Linked to original sources

The international spread of methicillin-resistant Staphylococcus aureus.

A genetic analysis of representative methicillin-resistant Staphylococcus aureus (MRSA) being isolated in London and Dublin hospitals has demonstrated that the epidemic strains from two London hospitals are different from the Dublin strains, but indistinguishable from the epidemic strains of eastern Australia. The possibility that some strains of MRSA are more likely than others to spread within hospitals is discussed.

Australia↗

Conjugative, staphylococcal plasmids carrying hitch-hiking transposons similar to Tn554: intra- and interspecies dissemination of erythromycin resistance.

Two staphylococcal plasmids, pWG4 and pWG25, encode production of a diffusible pigment and resistance to erythromycin and spectinomycin. The former was found occurring naturally in a clinical isolate of Staphylococcus aureus and the latter in S. epidermidis. Both plasmids are conjugative, capable of high-frequency, interspecies transfer, only isolated in the open-circular form and identical in molecular weight and pattern of restriction-endonuclease fragments. The only difference between the plasmids is in the expression of resistance, pWG4 encoding inducible and pWG25 constitutive erythromycin resistance. The resistance determinants of both plasmids behave as hitch-hiking transposons in cultural conditions that favour phage-mediated or phage-independent conjugation, always inserting a copy of themselves into the recipient's chromosome, except in S. epidermidis in which the chromosomal insertion site may be absent. The resistance determinants have been cloned and located on a 4 X 7 kbp EcoR1/HindIII restriction fragment which has a restriction map similar to that of the right arm of Tn554 (Murphy and Lofdahl, 1984). The hitch-hiking transposon of plasmid pWG25 has been designated Tn3853.

DNA Restriction Enzymes↗

Comparison of phage-mediated and conjugative transfer of staphylococcal plasmids in vitro and in vivo.

A strain of Staphylococcus aureus was constructed with which to compare transfer of resistance plasmids by the mechanisms of phage-mediated conjugation and conjugation. Transfer by each mechanism could be distinguished by the patterns of resistances transferred. Conjugation was favoured on dry absorbent surfaces, e.g., human skin, tissue and surgical gauze, whereas phage-mediated conjugation was favoured in fluids, e.g., milk and urine. The degree of hydration of the mating cells is postulated as one factor determining whether plasmids are transferred by phage-mediated conjugation or conjugation. Preliminary evidence indicates that topical creams and ointments affect the conjugative transfer of plasmids.

Anti-Bacterial Agents↗

Enzyme-linked immunosorbent assay for A and B water soluble blood group substances.

The conditions affecting an enzyme-linked immunosorbent assay for salivary blood group substances were investigated. It was found that A, B, and O secretor saliva samples would each bind both anti-A and anti-B typing reagents. The conditions that affected the assay response were optimized for maximum sensitivity and to give the highest resolution possible between the result for an antiserum binding to homologous antigen and the response for heterologous antigen-antibody combinations. Monoclonal antibodies eliminated the heterologous binding indicating that this binding was due to a lack of specificity of the routine typing reagents. A sensitive assay using the monoclonal antibodies to distinguish between samples of A and B secretor saliva is described.

ABO Blood-Group System↗

Some properties of the USP content-uniformity test as related to control charts and validation of solid dosage forms.

The statistical properties of the USP content-uniformity test have been investigated in detail in other reports. This note shows that control charts for the mean potency of a solid dosage form which are constructed using typical individual content-uniformity assays in conjunction with composite assay(s), show tight limits when the product has a high probability of passing the content-uniformity test. From a practical point of view, this is a strong argument in favor of the test and recommends the test as a quality control tool.

Pharmacopoeias as Topic↗

Transfer of plasmid-borne aminoglycoside-resistance determinants in staphylococci.

Aminoglycoside-resistance determinants in staphylococci are borne on conjugative and non-conjugative plasmids. The conjugative plasmids were found in methicillin-resistant strains of Staphylococcus aureus isolated recently in Darwin and Sydney, Australia and in Houston, Texas, USA. These plasmids and the class-2 conjugative plasmid reported by Archer and Johnston (1983) had similar patterns of EcoR1 restriction-endonuclease fragments, encoded resistance to gentamicin, kanamycin and neomycin, transferred to a non-lysogenic recipient in conditions that promoted close cell-to-cell contact and mobilised a small, non-conjugative plasmid. A further plasmid, pWG14, encoding resistance to kanamycin, neomycin, streptomycin, erythromycin and lincomycin, also displayed conjugative properties but did not mobilise the small, non-conjugative plasmid. The transfer frequency of all conjugative plasmids was stimulated by the addition of polyethylene glycol, particularly at concentrations above 20%, to mixtures of donor and recipient broth cultures. Polyethylene glycol appeared to promote close cell-to-cell contact between donor and recipient cells. A representative of the most common aminoglycoside-resistance plasmids in Australian isolates of methicillin-resistant S. aureus was non-conjugative and transferred by a bacteriophage-mediated system to a lysogenic recipient. With the exception of plasmid pWG14, the conjugative plasmids were also transferred by a bacteriophage-mediated system. Furthermore, cultural conditions that favoured conjugative transfer of plasmids inhibited bacteriophage-mediated transfer and vice versa. The efficacy of the two transfer systems for analysing the plasmids of gentamicin-resistant, methicillin-resistant isolates of S. aureus has been compared.

Aminoglycosides↗

Factorial designs in pharmaceutical stability studies.

An approach to analyzing and interpreting kinetic data from stability studies using factorial designs is presented. This may be useful for screening purposes or as an aid in identifying significant effects in complex systems. A typical 2n factorial experiment is discussed, and methods of variance estimation and statistical testing are presented. An example of simulated data is used to demonstrate how typical results may be analyzed, as well as the potential and limitations of this design in interpretation and construction of kinetic models.

Analysis of Variance↗

Computation of in-house quality control limits for pharmaceutical dosage forms based on product variability.

A method for establishing sampling plans for in-house limits that fix both the producer's and consumer's risks is presented for pharmaceutical systems in which both between-batch and within-batch variations are present. Such plans can always be constructed and require more or less sample assays depending on the variability of the process. The computations involve a numerical approximation to the bivariate normal distribution.

Analysis of Variance↗

Clinical significance of slow paroxysmal atrial tachycardia.

This study examines the clinical setting, characteristics, and follow-up of 173 patients who had slow paroxysmal atrial tachycardia (SPAT) (greater than 4 beats, rate less than 150 bpm) during 24-hour Holter monitoring. These episodes were classified by probable mechanism according to recognized ECG criteria and included AV nodal reentry (AVNR), sinoatrial nodal reentry (SANR), and automatic (A). There were 76 males (44%) with a mean age of 72 years and 97 females (56%) with a mean age of 73 years. The indications for Holter recording revealed that the SANR and A subgroups had a higher frequency of cerebral symptoms compared to AVNR (p less than 0.01). Chest pain was more common in the SANR group as compared to the other two groups (p less than 0.01). There was no difference in the frequency of palpitation in the three subgroups. The mean rate of SPAT for the entire group was 115.2 +/- 14 and these episodes had a mean duration of 5.58 +/- 3.07 seconds. The SANR subgroup had a significantly slower rate (107.1 +/- 9.2) as compared to the AVNR subgroup (p less than 0.01). One hundred fourteen patients were available for follow-up. The average period of follow-up was similar for all three groups. At follow-up the frequency of sick sinus syndrome as determined clinically and permanent pacemaker insertion was significantly greater in the SANR subgroup (p less than 0.01) as compared to the other subgroups which did not differ from each other.

Aged↗

Efficacy of sustained-release buccal nitroglycerin in patients with angina pectoris. New and long-acting therapy demonstrated by exercise.

The antianginal efficacy of a single sustained-release buccal nitroglycerin (BNTG) tablet was assessed in 16 patients with known coronary artery disease. Patients were trained in bicycle ergometry to induce angina pectoris within three to five minutes. A hemodynamically effective dose of BNTG was identified. Patients were tested at baseline and given placebo and BNTG in a randomized, double-blind manner on consecutive days. They were tested at 0.5, 1, 3, and 5 hours after drug administration. The average increase in exercise duration with BNTG compared with placebo at 0.5 hours was 40 percent (p less than 0.01); at 1 hour was 31 percent (p less than 0.01); at 3 hours was 27 percent (p less than 0.01); at 5 hours was 15 percent (p = NS). In a subset of ten patients in whom the tablet was maintained in the buccal pouch for five or more hours before dissolving, increase in exercise duration was significant at all times tested (p less than 0.05). We conclude that BNTG is an effective modality of administering nitroglycerin for rapid and prolonged effect with reduction in angina pectoris and increase in exercise duration which may persist for at least five hours.

Adult↗

Multicenter dose-response study of the effect of indapamide in the treatment of patients with mild to moderate hypertension.

This study, carried out in three centers in the United States, investigated the antihypertensive effect of three dosages of indapamide in 87 patients with mild to moderate hypertension. The dosages studied were 1 mg, 2.5 mg, and 5 mg daily. A double-blind, parallel study design was used with a six-week placebo run-in period followed by an eight-week treatment period and a two-week follow-up period. Compared with placebo, all dosages caused a significant decrease (P less than 0.05) in blood pressure, with an average decrease of approximately 6 mmHg diastolic and 13 mmHg systolic. The antihypertensive effect seemed to be fully manifest after six weeks of treatment. At all dosage levels, indapamide produced markedly greater therapeutic success rates than did the placebo. Success was defined as either a standing phase-5 diastolic blood pressure of less than 90 mmHg or a decrease by at least 10 mmHg from baseline. Although the decrease in mean serum potassium concentration was dose-related, the decrease was not clinically significant with any dose. A reduction in serum chloride and increases in serum uric acid and glucose were also observed. These changes were slight and did not cause the discontinuation of treatment for any patient. The most frequently observed side effects were mild to moderately severe dizziness, weakness, and headaches.

Adult↗