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Biomedical subjects

M L Barclay

Publications and source records attributed to M L Barclay.

At least 37 records · Page 2Linked to original sources
PubMed1996

Performance on the radiology component of a critical clinical skills examination.

RATIONALE AND OBJECTIVES: Clinical competence certification is now required in some specialties in medicine. A Comprehensive Clinical Assessment (CCA) was created to test mastery of critical skills by students at the end of the 3rd year of medical school. METHODS: The CCA is a series of stations that test skills the faculty consider important for all medical students (eg, breast examination, electrocardiogram reading, chest pain assessment, ophthalmology photographs). The radiology station was designed to evaluate imaging skills believed to be taught and learned in the core 3rd-year rotations. RESULTS: External measures (National Board Examinations, grade point average, and overall score) of clinical performance of the 608 medical students who completed the CCA examination between 1991 and 1993 were found to be correlated with the radiology station scores. CONCLUSION: The radiology station in the CCA examination is a reproducible measure of clinical performance.

Certification↗
PubMed1996

Adaptive resistance to tobramycin in Pseudomonas aeruginosa lung infection in cystic fibrosis.

Aminoglycoside antibiotics have been shown to induce adaptive resistance in Pseudomonas aeruginosa in vitro and in a mouse model of infection, but adaptive resistance has not been described in human infections. Seven patients with cystic fibrosis were treated with inhaled tobramycin to determine whether adaptive resistance occurred in P. aeruginosa in their sputum. In three patients who had not recently taken antibiotics, 80 mg tobramycin was administered by nebuliser and resulting peak sputum tobramycin concentrations were 90-240 mg/L (elimination half-life 1.9-2.1 h). Adaptive resistance was detected in P. aeruginosa 1-4 h after the dose of tobramycin. Moderate resistance was present at 24 h and full susceptibility returned between 24 and 48 h. In four other patients on long-term twice-daily inhaled aminoglycoside treatment, adaptive resistance was present before, and 4 h after, 80 mg of tobramycin administered by nebuliser. The presence and time course of adaptive resistance in humans may have implications for improving aminoglycoside dosing regimens.

Adolescent↗
PubMed1996

The effect of aminoglycoside-induced adaptive resistance on the antibacterial activity of other antibiotics against Pseudomonas aeruginosa in vitro.

The effect of gentamicin-induced adaptive resistance on the antibacterial activity of six non-aminoglycoside antibiotics was studied. Adaptive resistance was induced in Pseudomonas aeruginosa in a dynamic in-vitro model of infection. The bactericidal effect of ceftazidime, imipenem, aztreonam, ciprofloxacin, and piperacillin was not altered in the presence of adaptive resistance but the effect of rifampicin was increased.

Anti-Bacterial Agents↗
PubMed1996

Prospective, randomized, controlled study comparing two dosing regimens of gentamicin/oral ciprofloxacin switch therapy for acute pyelonephritis.

Aminoglycosides are drugs of choice for severe gram-negative urinary tract sepsis. Recent evidence suggests that they are just as efficacious, but less nephrotoxic and ototoxic, if given as a single daily dose rather than in divided doses. We considered that a single, large dose of an aminoglycoside followed by oral therapy with a different antibiotic might be equally effective and possibly less toxic. This randomized, controlled study compared a single large i.v. dose (10 mg/kg) of gentamicin (S) with a standard multiple dose regimen (M) of gentamicin (2.5 mg/kg i.v. stat and then computer generated divided doses aiming for peak and trough concentrations of 8 and 1.5 mg/l respectively) for the treatment of patients with suspected acute pyelonephritis requiring hospitalization for parenteral antibiotic treatment. All patients were switched to oral ciprofloxacin either four hours after the S dose or when clinically appropriate in the M regimen. For all patients the total duration of treatment was five days. Fifty-three patients (48 women; mean age 32 yr) were enrolled. Clinical and bacteriological efficacy could be assessed in 41 patients. Thirteen of 16 in the S arm and 24 of 25 in the M arm were clinically cured and the other four clinically improved. Fifteen of 16 in the S arm and 23 of 25 in the M arm were cured bacteriologically (sterile urine 7-10 days after treatment). In 41 patients high tone audiometry was carried out before or very soon after the start of treatment, and again at the end of treatment. Ototoxicity (> or = 10 dB loss in > or = 2 frequencies in both ears) was observed in 3 of 18 in the S group (17%) and 7 of 23 in the M group (30%) (NS). Other side-effects and toxicity were mild and not different between groups. Substantial cost savings occurred in the S group. In summary, a large single dose of gentamicin was comparable in efficacy and toxicity to a standard regimen, but cheaper and more convenient to use.

Acute Disease↗
PubMed1995

A computer model of uterine contractions based on discrete contractile elements.

OBJECTIVE: To predict uterine contraction waveforms using a microcomputer-based model of uterine activity based on discrete contractile elements, varying the shape of the model, total number of cells, and pacemaker locations. METHODS: The model is a hollow ovoid composed of discrete contractile elements (cells) that propagate electrical impulses, generate tension, and have defined contracting and refractory periods. Each cell contacts eight surrounding cells and propagates impulses iteratively from cell to cell. Contraction pressure is the sum of the tension contributions by contracting cells. Sample contraction waveforms were generated based on various numbers of cells organized in ovoids with long:short axis ratios of 1:1, 3:2, and 2:1, with one or two pacemakers at varying positions. RESULTS: Contraction waveforms are altered by altering the shape of the matrix, but not by increasing the number of contractile elements. The vertical placement of the pacemaker has a dramatic effect on the shape and symmetry of contractions, including the development of patterns characteristic of "dysfunctional" uterine contractions. CONCLUSION: Abnormal uterine contraction patterns may result from pacemaker activity in unusual locations, such as mid-uterus. Further refinement of this computer model of uterine activity may contribute to a better understanding of the genesis of normal and abnormal intrauterine pressure waveforms and their relationship to the progress of labor.

Computer Simulation↗
PubMed1995

Experience of once-daily aminoglycoside dosing using a target area under the concentration-time curve.

BACKGROUND: Many centres are changing to once-daily aminoglycoside administration. However, proposed methods for this practice often have theoretical and practical difficulties. We have developed a method in which a target area under the concentration-time curve (AUC) is used instead of traditional peak and trough serum concentrations. AIMS: To analyse our experience with the target AUC method in the first 100 courses of once-daily aminoglycoside administration in the Christchurch, New Zealand hospitals. METHODS: Following a starting dose of 5-7 mg/kg, administered by 30-minute infusion, the AUC was calculated using two serum aminoglycoside concentrations taken at one and six-14 hours after the start of the infusion. Dose adjustment was made to correct for any difference between the calculated AUC and a target AUC (72-101 mg.1(-1).h). The method was assessed for practicality and precision in 100 courses of treatment. The incidence of aminoglycoside toxicity was documented. RESULTS: The mean final dose of 6.68 mg/kg, and AUC of 92.8 mg.1(-1).h, were significantly different from the mean starting dose and AUC of 5.67 mg/kg and 74.0 mg.1(-1).h, respectively. The method appeared to be more precise than empirical dosing at achieving the target AUC even though the final recommended dose had more variability than the starting dose. Although the study was uncontrolled, observed nephrotoxicity (2%) and ototoxicity (up to 6.9%) were no greater than expected from the results of other studies. There were no deaths related to antibiotic failure. CONCLUSIONS: The AUC method was practical, and more appropriate for once-daily dosing than the conventional method of aiming for target peak and trough concentrations. Dose adjustment can be made before the next dose.

Adolescent↗
PubMed1995

Improved efficacy with nonsimultaneous administration of first doses of gentamicin and ceftazidime in vitro.

First doses of aminoglycoside and beta-lactam antibiotics, when used in combination, are usually given simultaneously; however, nonsimultaneous administration may be more efficacious. We used a dynamic in vitro model, which simulates in vivo serum kinetics, to assess the effect of spacing the first doses of gentamicin and ceftazidime used against Pseudomonas aeruginosa ATCC 27853 and two clinical isolates of P. aeruginosa, PA1 and PA2. The following dose regimens against P. aeruginosa ATCC 27853 were compared: (i) gentamicin given alone, (ii) ceftazidime given alone, (iii) gentamicin and ceftazidime given simultaneously, (iv) gentamicin followed by ceftazidime at 15 or 50 min or at 2, 4, or 8 h, and (v) ceftazidime which was followed by gentamicin at 4 h. The effects of regimen iii and the 4-h interval in regimen iv against PA1 and PA2 were also compared. Initial peak concentrations used were 8 mg/liter for gentamicin and 80 mg/liter for ceftazidime, with drug half-lives of 2.5 and 1.8 h, respectively. Compared with simultaneous administration, nonsimultaneous administration (regimens iv and v) produced greater overall bacterial killing and was associated with a delay in bacterial regrowth (p < 0.005) of up to 6.6 to 8.3 h, regardless of the order in which the drugs were given. The optimal interval between gentamicin and ceftazidime doses, which maximized initial bactericidal effect and the time before regrowth, appeared to be 2 to 4 h.

Ceftazidime↗
PubMed1995

Aminoglycosides--50 years on.

1. The aminoglycoside antibiotics are 50 years old. Their success and continuing use can be attributed to various factors including rapid concentration-dependent bactericidal effect, synergism with beta-lactam antibiotics, clinical effectiveness, a low rate of true resistance and low cost. 2. The aminoglycosides remain drugs of choice in many circumstances including septicaemia, other serious infections due to Gram negative bacilli, and bacterial endocarditis. 3. Nephrotoxicity and ototoxicity have been the main drawbacks clinically for the aminoglycosides. 4. There has been an evolution in dosing strategies largely aimed at reducing toxicity. Therapeutic drug monitoring has been used extensively to assist dosing, and target concentrations have been advocated, such as peak concentrations of between 6 and 10 mg l-1 and through concentrations of < 2 mg l-1 for gentamicin, tobramycin and netilmicin. 5. Recently there has been a minor revolution in the approach to aminoglycoside dosing, with a change to larger doses, given less frequently. In its most convenient form this is 'Once-daily aminoglycoside dosing'. It offers the hope of better efficacy, less toxicity, and easier administration and monitoring. 6. This article summarises the background of aminoglycoside usage, leading up to the recent changes in dosing strategy.

Aminoglycosides↗
PubMed1995

A suggested approach to once-daily aminoglycoside dosing.

1. Once-daily aminoglycoside dosing has many advantages and has been widely advocated. However, existing guidelines for methods of administration and monitoring are non-specific and may lead to excessive dosing. 2. The traditional approach of aiming for target peak and trough concentrations is not appropriate for once-daily dosing. 3. A method is proposed which uses a target area under the concentration-time curve (AUC) for the aminoglycoside based on the 24 h AUC that would result with conventional dosing. This method requires measurement of two drug concentrations, one approximately 0.5 h after the end of the infusion and another at a later time (6-22 h) depending on renal function. 4. A simpler, graphical method is also proposed for patients with normal renal function, which requires the measurement of a single concentration at a time between 6 and 14 h. 5. Both methods are likely to be safer than existing guidelines.

Aminoglycosides↗
PubMed1994

Effect of search experience on sustained MEDLINE usage by students.

PURPOSE: While educators agree that medical students should learn to use MEDLINE for clinical application, there is a lack of consensus on an optimal level of exposure to this resource during training that will result in sustained usage. This study sought to identify the level of search experience (1) to increase the odds that the student searcher will continue to search MEDLINE in the absence of search assignments, and (2) to make an appreciable difference in the odds of retrieving items of relevance from the MEDLINE database. METHOD: Search frequencies of MEDLINE via the PaperChase interface by 184 fourth-year students (class of 1992) at the University of Michigan Medical School were analyzed using the log cross-product technique. The students were required to take the Comprehensive Clinical Assessment, an examination that included a search assignment, as they entered their fourth year of medical school. Their levels of MEDLINE use and their retrieval performances before the examination were compared with those achieved during the subsequent five months as fourth-year medical students. RESULTS: For those who searched an average of at least once a month during their first three years of medical school, there was a 7.38:1 chance that they would conduct three searches per month in the fourth year, compared with those who searched less frequently. The odds of retrieving at least one item of definite relevance were 8.27:1 for those who had searched at least one and one-half times per month before the search assignment. CONCLUSION: Searching once a month through the first few years of medical school provided an experience level that improved the odds that a student would continue to search MEDLINE: Data indicated that a history of a minimum of 1.5 online sessions per month increased the odds of retrieving relevant items to 8.27:1. Implications for educational strategy are clear.

Education, Medical, Undergraduate↗
PubMed1994

Lithium associated thyrotoxicosis: a report of 14 cases, with statistical analysis of incidence.

OBJECTIVE: Lithium is known to cause goitre and hypothyroidism, and has been associated less commonly with hyperthyroidism. We report a series of 14 patients with lithium associated thyrotoxicosis (LiAT), and have used epidemiological data to assess the association between long-term lithium treatment and the development of thyrotoxicosis. DESIGN: Information for this retrospective study was obtained from records of patients attending the thyroid clinic between 1973 and 1991. Statistical analysis of the association between long-term lithium treatment and incidence of thyrotoxicosis was made using local thyrotoxicosis incidence figures and lithium prescription data. MEASUREMENTS: Investigations included 99mTc pertechnetate thyroid scans, and blood analyses to measure serum T4, serum T3, free T4 index, and thyroid microsomal and thyroglobulin antibody titres. RESULTS: During the 18-year period there were 14 patients with LiAT. This number of cases of thyrotoxicosis occurring in patients on lithium was more than three times greater than that predicted from local thyrotoxicosis incidence rates (P < 0.05). Scintiscans were obtained for 13 patients: 8 had toxic diffuse goitre, 2 toxic multinodular goitre, 1 toxic uninodular goitre, and 2 had a lack of visualization consistent with 'painless thyroiditis'. Nine patients received a course of carbimazole and 6 of these remain in remission. Six patients have received 131I therapy. Eight patients have become hypothyroid at follow-up (5 post 131I, 1 following a course of carbimazole, and the 2 with 'painless thyroiditis'). CONCLUSIONS: Statistical analysis has shown that long-term lithium therapy is associated with an increased risk of thyrotoxicosis. LiAT is a heterogeneous condition with differing underlying thyroid pathologies and the mechanisms remain uncertain. The management of LiAT should initially be with antithyroid medication, and 131I therapy should be given only to patients who do not obtain long-term remission.

Adolescent↗
PubMed1994

Efficacies of different vancomycin dosing regimens against Staphylococcus aureus determined with a dynamic in vitro model.

A dynamic in vitro model was used to assess four different vancomycin dosing regimens against Staphylococcus aureus. These regimens achieved peak drug concentrations of 48 micrograms/ml (single dose) and 30 micrograms/ml (dosed every 12 h) and constant concentrations of 16 and 8 micrograms/ml. Analysis of the area under the bacterial concentration-time curve, area under the first moment of the bacterial concentration-time curve, and bacterial elimination rate constant showed no difference in the rate or extent of bacterial killing. The optimal dosing method may be that which achieves the lowest area under the curve while concentrations are maintained above the MBC.

Dose-Response Relationship, Drug↗
PubMed1994

What is the evidence for once-daily aminoglycoside therapy?

Aminoglycosides are important antibacterial agents for the treatment of serious infection. Evidence suggests that high peak plasma concentrations must be achieved early in the course of treatment if these agents are to be effective, but prolonged high concentrations may cause ototoxicity and nephrotoxicity. Peak plasma concentrations of 6 to 10 mg/L and trough concentrations of less than 2 mg/L for gentamicin and tobramycin have been traditional goals of therapy. Extensive recent evidence from in vitro, animal and human studies suggests that these target concentrations need revision. Aminoglycosides display concentration-dependent bacterial killing, have a long postantibiotic effect, and induce adaptive resistance in Gram-negative bacteria. All of these factors support the use of larger doses of aminoglycosides that are given less frequently than conventional therapy. Studies in vitro support this approach, showing greater activity when aminoglycosides are given less frequently. Animal studies comparing different dosage intervals have shown varying results, with only a slight bias favouring the longer dosage interval. However, the short elimination half-lives for the drugs in animals limit the applicability of these models to humans. Importantly, there is convincing evidence in animal studies that nephrotoxicity and ototoxicity are both reduced when the same total daily dose is administered in less frequent doses. There have been at least 29 clinical trials comparing once-daily administration of aminoglycosides with conventional administration 2 to 4 times daily. In general, efficacy has not been shown to be different between regimens, although one trial showed an advantage for once-daily administration compared with administration 3 times daily. A small number of trials have shown less nephrotoxicity and ototoxicity with once-daily administration, leading several authors to suggest that there is sufficient evidence to warrant a change to once-daily administration of aminoglycosides. However, once-daily administration has not been well studied in the paediatric population, or in patients with renal failure or endocarditis, and cannot be recommended in these patients as yet. The choice of a 24-hour dosage interval is somewhat arbitrary, and the optimal interval may not necessarily be 24 hours. No studies have included dosage adjustment based on pharmacokinetic modelling methods, and the effect of this on treatment outcome needs to be assessed. The best method of administering aminoglycosides once daily is yet to be determined.

Aminoglycosides↗
PubMed1993

Factors affecting students' use of MEDLINE.

MEDLINE search transcripts by a class of third-year medical students were analyzed. The 184 students were divided into three groups according to their search experience in terms of the number of sessions logged at the time of a search assignment. A strong relation was found between the level of search experience and the frequency of use in the subsequent 5 months. Over 80% of the students were able to retrieve a few useful items for an emergency clinical situation. More experienced searchers were able to retrieve more relevant items than less experienced searchers. However, no relation was found between search effectiveness and clinical knowledge as indicated by two scores derived from the University of Michigan's Comprehensive Clinical Assessment examination and Part II of NBME. Similarly, clinical knowledge also did not appear to relate to MEDLINE search experience. More exposure to MEDLINE during medical school could play an important role in developing effective literature searching skills for lifelong learning, which is essential for today's health professionals.

Clinical Competence↗
PubMed1992

Adaptive resistance following single doses of gentamicin in a dynamic in vitro model.

Adaptive resistance is a phenomenon recently described for Pseudomonas aeruginosa and other gram-negative bacilli following exposure to aminoglycoside antibiotics. It is a reversible form of resistance which develops within 1 to 2 h of initial exposure to an aminoglycoside and disappears several hours after removal of the antibiotic. We investigated adaptive resistance in P. aeruginosa ATCC 27853 following single doses of gentamicin by using a dynamic in vitro model which mimics in vivo pharmacokinetics. The initial peak gentamicin concentrations were 2.5, 8, and 25 mg/liter, and these were followed by an exponential decay in the concentration, with a half-life of 2.5 h. The degree of adaptive resistance was greater and the duration was longer with higher initial gentamicin concentrations. Maximal adaptive resistance occurred between 2 and 10 h following 8 mg/liter and between 2 and 16 h following 25 mg/liter. Full recovery of susceptibility occurred at approximately 36, 39, and 43 h following 2.5, 8, and 25 mg/liter, respectively, at which times the gentamicin concentrations were extremely low. Longer dosing intervals for aminoglycosides may improve efficacy by allowing time for adaptive resistance to resolve.

Drug Resistance, Microbial↗