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Biomedical subjects

C J Walker

Publications and source records attributed to C J Walker.

At least 37 records · Page 2Linked to original sources

Performance appraisal of online MEDLINE access routes.

OBJECTIVE: To compare the performance and cost of 11 online MEDLINE systems with MEDLINE at Elhill. DESIGN: Comparative study. SYSTEMS: Eleven online daytime systems commercially available in North America offering the MEDLINE database. MEASURES: Number of relevant citations, number of irrelevant citations, proportion of searches producing no relevant citations and cost per relevant citation were analyzed for each system. Relevance and cost for each system were compared with direct searching of MEDLINE through NLM for librarian and clinician search strategies for 18 clinical questions. The citations retrieved by both strategies were pooled and rated for relevance on a 7-point scale. RESULTS: Numbers of relevant and irrelevant citations and cost per relevant citation were higher for clinician searches than librarian searches, reflecting the higher total number of citations retrieved by the clinician approaches. A lower proportion of clinician searches produced no relevant citations than librarian searches. CONCLUSIONS: Eleven daytime MEDLINE systems performed similarly in terms of retrieval and cost within similar searching groups. Clinicians, however, tended to capture larger overall retrievals resulting in higher numbers of relevant and irrelevant citations than librarians.

CD-ROM↗

Increases in knowledge and use of information technology by entering medical students at McMaster University in successive annual surveys.

OBJECTIVE: To determine self-reported microcomputer and information technology competency, access, and usage by entering medical students and their perceptions of the need for training in additional applications. DESIGN: Cross-sectional surveys of successive classes. SETTING: McMaster University Faculty of Health Sciences Medical Undergraduate Program, which has a 33-month, problem-based, self-directed learning curriculum and a high applicant-to-student ratio. PARTICIPANTS: Medical school classes entering in 1987, 1988, and 1989. Response rates were 80%, 90%, and 86% respectively. MEASURES: A self-report questionnaire was sent to each student, with up to two follow-up letters to prompt a response. RESULTS: There was a progressive rise in reported information technology access and use for the three years. For the classes starting in 1987, '88, and '89 respectively, computer access was 29%, 49%, and 49% (P < 0.002 for linear trend), and, among those with computer access, modem access was 17%, 29% and 50% (P = 0.012). Self-service MEDLINE use on CD-ROM at the Health Sciences Library was 65%, 75%, and 89% respectively (P < 0.001) for all respondents within the first few months of starting medical school. Over 50% of each class stated they would take courses, if available, on clinical applications software, office management, online searching, filing, and CD-ROM searching. CONCLUSIONS: Half of the most recent entering students already had access to a personal computer and most wished to learn computer applications that would assist them with patient management, and with information access and organization. Medical schools need to address which applications they will teach or make available and how to bring all students to acceptable competency in their use.

Computer Literacy↗

In vitro assay of the chlorophyll biosynthetic enzyme Mg-chelatase: resolution of the activity into soluble and membrane-bound fractions.

The first committed step in chlorophyll synthesis is the Mg-chelatase-catalyzed insertion of magnesium into protoporphyrin IX. Since iron insertion into protoporphyrin leads to heme formation, Mg-chelastase lies at the branch point of heme and chlorophyll synthesis in chloroplasts. Little is known about the enzymology or regulation of Mg-chelatase, as it has been assayed only in intact cucumber chloroplasts. In this report we describe an in vitro assay for Mg-chelatase. Mg-chelatase activity in intact pea chloroplasts was 3- to 4-fold higher than in cucumber chloroplasts. This activity survived chloroplast lysis and could be fractionated by centrifugation into supernatant and pellet components. Both of these fractions were required to reconstitute Mg-chelatase activity, and both were inactivated by boiling indicating that the enzyme is composed of soluble and membrane-bound protein(s). The product of the reaction was confirmed fluorometrically as the magnesium chelate of the porphyrin substrate. The specific activity of the reconstituted system was typically 1 nmol of Mg-deuteroporphyrin per h per mg of protein, and activity was linear for at least 60 min under our assay conditions. ATP and magnesium were required for Mg-chelatase activity and the enzyme was sensitive to the sulfhydryl reagent N-ethylmaleimide (I50, 20 microM). Broken and reconstituted cucumber chloroplasts were unable to maintain Mg-chelatase activity. However, the cucumber supernatant fraction was active when combined with the pellet fraction of peas; the converse was not true, which suggested that the cucumber pellet was the component that lost activity during lysis.

Journal Article↗

Synthesis of divinyl protochlorophyllide. Enzymological properties of the Mg-protoporphyrin IX monomethyl ester oxidative cyclase system.

The resolution and reconstitution of the Mg-protoporphyrin IX monomethyl ester oxidative cyclase system into a supernatant and a pellet fraction was accomplished by a procedure involving salt treatment followed by osmotic shock. Recombination of pellet and supernatant fractions was required for cyclase activity. This restoration effect could be demonstrated using either Mg-protoporphyrin IX or Mg-protoporphyrin IX monomethyl ester as the cyclase substrate in the presence or absence of S-adenosylmethionine. Pretreatment of the pellet fraction with either 8-hydroxyquinoline or desferal mesylate inhibited cyclase activity, indicating that there is a heavy-metal-ion requirement in this fraction. The cyclase supernatant protein(s) was not internalized by Sephadex G-50 and did not bind to Blue Sepharose, suggesting that it has a molecular mass of over 30 kDa and that it does not bind the cofactor NADPH. The cyclase supernatant protein did bind to MgProtoMe2-bound Sepharose and could be eluted by raising the pH to 9.7 in the presence of 4 mM-n-octyl glucoside. The pH optimum of the cyclase was 9.0. About a 40-fold purification of the cyclase supernatant protein was achieved by a combination of (NH4)2SO4 fractionation and phenyl-Sepharose chromatography.

Ammonium Sulfate↗

Rapid evolution of microcomputer use in a faculty of health sciences.

OBJECTIVE: To assist with educational planning we surveyed health sciences faculty members in 1989 to determine their use of microcomputers, desire for further instruction and perceptions on what microcomputer services should be provided for students. The 1989 results were compared with those of a similar survey performed in 1986. DESIGN: A self-completed, mailed questionnaire, with up to three reminders. SETTING: Faculty of Health Sciences, McMaster University, Hamilton, Ont. PARTICIPANTS: All full-time (FT) and part-time (PT) faculty members were sent the questionnaire; over 80% of the FT and 65% of the PT faculty members responded in 1986 and in 1989. RESULTS: The proportions of faculty members who used microcomputers increased significantly over the 3 years, from 71% to 87% among FT members (p = 2.2 x 10(-8)) and from 48% to 69% among PT members (p = 4.9 x 10(-8)). There were significant increases in the use of many of the applications, especially database and filing uses (from 10% to 41% among FT members [p less than 1 x 10(-9)] and from 6% to 34% among PT members [p less than 1 x 10(-9)]) and on-line access to bibliographic databases (from 7% to 37% among FT members [p less than 1 x 10(-9)] and from 3% to 18% among PT members [p less than 1 x 10(-9)]. These changes occurred mainly through individual initiative and voluntary continuing education. CONCLUSIONS: The extraordinary rate of adoption of microcomputers attests to their perceived usefulness. Curriculum planners need to consider how the success of microcomputer applications can be evaluated objectively and how successful applications can be integrated into educational programs.

Attitude of Health Personnel↗

Further characterization of the magnesium chelatase in isolated developing cucumber chloroplasts : substrate specificity, regulation, intactness, and ATP requirements.

Mg-chelatase catalyzes the first step unique to the chlorophyll branch of tetrapyrrole biosynthesis, namely the insertion of Mg into protoporphyrin IX (Proto). Mg-chelatase was assayed in intact chloroplasts from semi-green cucumber (Cucumis sativus, cv Sumter) cotyledons. In the presence of Proto and MgATP, enzyme activity was linear for 50 minutes. Plastid intactness was directly related to (and necessary for) Mg-chelatase activity. Uncouplers and ionophores did not inhibit Mg-Chelatase in the presence of ATP. The nonhydrolyzable ATP analogs, beta,gamma-methylene ATP and adenylylimidodiphosphate, could not sustain Mg-chelatase activity alone and were inhibitory in the presence of ATP (I(50) 10 and 3 millimolar, respectively). Mg-chelatase was also inhibited by N-ethylmaleimide (I(50), 50 micromolar) and the metal ion chelators 2,2'-dipyridyl and 1, 10 phenanthroline (but not to the same degree by their nonchelating analogs). In addition to Proto, the following porphyrins acted as Mg-chelatase substrates, giving comparable specific activities: deuteroporphyrin, mesoporphyrin, 2-ethyl, 4-vinyl Proto and 2-vinyl, 4-ethyl Proto. Mg-chelatase activity and freely exchangeable heme levels increased steadily with greening, reaching a maximum and leveling off after 15 hours in the light. Exogenous protochlorophyllide, chlorophyllide, heme, and Mg-Proto had no measurable effect on Mg-chelatase activity. The potent ferrochelatase inhibitors, N-methylmesoporphyrin and N-methylprotoporphyrin, inhibited Mg-chelatase at micromolar concentrations.

Journal Article↗

Localization of minoxidil sulfotransferase in rat liver and the outer root sheath of anagen pelage and vibrissa follicles.

The precise biochemical mechanism and site(s) of action by which minoxidil stimulates hair growth are not yet clear. Minoxidil sulfate is the active metabolite of minoxidil, with regard to smooth muscle vasodilation and hair growth. Formation of minoxidil sulfate is catalyzed by specific PAPS-dependent sulfotransferase(s) and minoxidil-sulfating activities have been previously reported to be present in liver and hair follicles. One of these minoxidil-sulfating enzymes has been purified from rat liver (rat minoxidil sulfotransferase, MST) and a rabbit anti-MST antibody has been prepared. Using this anti-MST antibody, we have immunohistochemically localized minoxidil sulfotransferase in the liver and anagen hair follicles from rat. In rat pelage and vibrissa follicles, this enzyme is localized within the cytoplasm of epithelial cells in the lower outer root sheath. Although the immunolocalization of MST might not necessarily correlate with the MST activity known to be present in anagen follicles, the results of this study strongly suggest that the lower outer root sheath of the hair follicle may serve as a site for the sulfation of topically applied minoxidil.

Animals↗

Effect of administration of human chorionic gonadotrophin on criteria used to assess testosterone administration in athletes.

Abnormal ratios of testosterone to epitestosterone (T/E) and testosterone to LH (T/LH) in the urine of male athletes are indicative of testosterone administration. The T/E ratio has been adopted by the International Olympic Committee as the sole criterion used in the detection of testosterone administration. An athlete is usually considered to have failed a drug test if the urinary T/E ratio is greater than 6. Human chorionic gonadotrophin (hCG) has been used by some male athletes to stimulate testicular secretion of testosterone. The purpose of this investigation was to examine whether the urinary T/E ratio can remain unaffected by administration of hCG to normal adult males. Administration of hCG resulted in large increases in serum testosterone concentrations and urinary T/LH ratios but small changes in urinary T/E ratios of two subjects (maximum T/E values observed were 0.8 and 1.2 respectively). These observations suggest that the urinary T/LH ratio is a valuable indicator of hCG as well as of testosterone administration. This study is the first to measure urinary T/LH ratios using the technique of gas chromatography-mass spectrometry for quantification of testosterone, and highly specific monoclonal antibodies for the measurement of LH. An ultrafiltration method is proposed as part of a confirmatory procedure to be adopted in the measurement of urinary gonadotrophins for drug control in sport.

Chorionic Gonadotropin↗

A study to enhance clinical end-user MEDLINE search skills: design and baseline findings.

OBJECTIVE: To determine if a preceptor and timely, individualized feedback improves the performance of physicians in searching MEDLINE using GRATEFUL MED in clinical settings. DESIGN: Randomized controlled trial. SETTING: A 300 bed primary to tertiary care teaching hospital. Computers were installed in wards and clinics of 6 major clinical services, and the emergency room, intensive care and neonatal intensive care units. SUBJECTS: All physicians and physicians-in-training from the departments of Medicine, Family Medicine, Surgery, Psychiatry, Pediatrics, and Obstetrics and Gynecology were included if they made patient care decisions for at least 8 weeks during the study period. INTERVENTION: All participants were given a 1-hour training class and 1 hour of individualized searching with 1 of the 2 study librarians. After training, participants were randomized to a control group who received no further intervention or to an intervention group in which each person chose a clinical preceptor experienced in MEDLINE searching and received individualized feedback by a study librarian on their first 10 searches, indicating search quality and providing suggestions for improvement. Feedback was mailed the first week day after the search was done. MAIN MEASURES: Baseline characteristics by study group, department and level of training, study participation rates, and searching rates. MAIN RESULTS: 308 of 392 eligible physicians joined the study. Participation was almost 80% with some variation by department and level of training. Excellent balance in the baseline characteristics was achieved for the 2 groups, as well as for the number who did first searches. Intervention group participants searched MEDLINE more often than did controls (3.5 searches per month vs 2.5 per month for controls, P = 0.046). The recall and precision for first searches for both groups was significantly less than that of librarians. The analysis of study data will be completed by September 1991. CONCLUSIONS: Clinicians are willing to do self-service searching of MEDLINE in clinical settings but their precision and recall are less than a trained librarian at baseline. Search skills enhancements are needed and the effect of feedback and preceptors is being tested. SOURCE OF FUNDING: U.S. National Library of Medicine and Ontario Ministry of Health.

Computer User Training↗

Online access to MEDLINE in clinical settings: impact of user fees.

The effect of introducing user fees on the frequency and quality of MEDLINE searching with GRATEFUL MED by physicians in clinical settings was tested. After training and free use (prior study), consenting participants were randomly allocated to pay searching costs (pay group) or continue without fees (no pay group). Fifty-nine physicians participated. Among the prior study's frequent searchers, the pay group searched at less than one third of the rate of those assigned to no pay. For less frequent searchers in the prior study, only 48% of those assigned to pay did any searches, compared with 85% for the no pay group (P = 0.006), and for those who did search, their frequency was almost half. However, there was no significant difference in the quality of searches; both groups demonstrated about equivalent recall (P = 0.77), but significantly lower precision (P = 0.03) than for the librarian's independent searches. Similarly, there was no difference in the proportion of searches affecting clinical decisions for the two groups. Thus, imposing user charges for online searching in clinical settings after a period of free use adversely affects searching quantity, but not quality. MEDLINE providers should consider whether user fees will undermine its benefits.

Fees and Charges↗

Online access to MEDLINE in clinical settings. A study of use and usefulness.

STUDY OBJECTIVE: We introduced self-service access to the medical literature database, MEDLINE, into clinical settings to assess the frequency, patterns, purposes, and success of use. DESIGN: Longitudinal descriptive study. SETTING: Inpatient and outpatient services of a university medical center. PARTICIPANTS: All trainees and attending staff working at the service sites were invited to participate; 158 (84%) did so. INTERVENTIONS: Free online access was provided to MEDLINE through GRATEFUL MED software. Participants were offered a 2-hour introduction to online searching and 2 hours of free search time. MEASUREMENTS AND MAIN RESULTS: For each search, a computer program requested identification of the user and the question to be addressed. Search transactions were recorded automatically. Interviews were conducted after a random sample of searches, and search questions were given to more expert searchers to run for comparison with the original. Eighty-one percent of participants did searches on study computers, at a mean rate of 2.7 searches per month. On comparison searches, participants retrieved 55% of the number of relevant articles retrieved by reference librarians (P = 0.024) and 50% more irrelevant articles (P less than 0.001). Forty-seven percent of searches on patient problems affected clinical decisions, but often on scanty information. CONCLUSIONS: MEDLINE searching from clinical settings is feasible with brief training and affects clinical decisions. However, inexperienced searchers miss many relevant citations and search inefficiently. Further studies are needed to assess the impact of searching on physician performance and patient care.

Academic Medical Centers↗

Immunohistochemical and autoradiographic findings suggest that minoxidil is not localized in specific cells of vibrissa, pelage, or scalp follicles.

Immunohistochemistry with a minoxidil antibody suggested that minoxidil-immunoreactivity is associated with the root sheaths, laterally orientated differentiating matrix cells, and dividing epithelial cells of cultured vibrissa follicles of pigmented and albino neonatal mice. The dermal papilla and connective tissue sheath were devoid of minoxidil-immunoreactivity. To verify that minoxodil-immunoreactivity in the follicles was specific, immunostaining was conducted with dissected whisker pads, formalin-fixed "dead" follicles, and sections of spleen, liver and kidney (non-haired organs) cultured with minoxidil. Microscopic examination revealed minoxidil-immunoreactivity in all of these tissues. Follicles and whisker pads cultured with minoxidil, then washed for one h in media were devoid of minoxidil-immunoreactivity. These data suggest that minoxidil-immunoreactivity in cultured vibrissa follicles is probably non-specific. Sections of skin from C3H and CF1 mice which were topically dosed with minoxidil (in vivo) showed no minoxidil-immunoreactivity. Autoradiography demonstrated that tritiated minoxidil was bound in vivo and in vitro only to melanin granules in pigmented follicles of rodent and human tissue. This is probably non-specific binding since melanin is known to accumulate several chemically and pharmacologically unrelated drugs. It is reasonable to conclude that, under the conditions of these experiments, minoxidil is not specifically localized in any cells of whisker, pelage or, scalp follicles.

Animals↗

Donor site morbidity following osteocutaneous free fibula transfer.

Nine patients who had undergone free fibula transfer were reviewed to determine the incidence of donor site complications. Problems identified included distal oedema, cold intolerance, sensory loss and weakness. However, the functional deficit was not great and most patients were not troubled by their symptoms. More serious potential complications from raising this flap are considered.

Adult↗

Incorporation of atmospheric oxygen into the carbonyl functionality of the protochlorophyllide isocyclic ring.

Detached cucumber (Cucumis sativus L. var. Beit Alpha) cotyledons incubated in darkness with 5-aminolaevulinic acid and either 16O2 air (control) or 18O2 in N2 accumulated protochlorophyllide. This was converted into methyl phaeoporphyrin alpha 5 and analysed by mass spectrometry. The molecular ion of the methyl phaeoporphyrin alpha 5 derived from the 18O2 incubation was 2 mass units greater than that of the control, establishing that the oxo oxygen atom of the isocyclic ring is derived from atmospheric oxygen.

Atmosphere↗

Cross-over study of fat-corrected forearm mineral content during nandrolone decanoate therapy for osteoporosis.

We have previously reported an increase in forearm bone mineral content (BMC) during therapy for osteoporosis with the anabolic steroid, nandrolone decanoate. However, it has recently been claimed that part of this increase is spurious, due to a decrease in forearm fat during the treatment. We have therefore analyzed the data from a cross-over study of the effects of this agent on 70 osteoporotic women, using the fat correction procedure supplied by the manufacturer of the forearm densitometer. There was a significant rise (p less than 0.001) in the mean fat-corrected BMC (BMC[fc]) on nandrolone decanoate (50 mg intramuscularly every 2 or 3 weeks) and a non-significant fall in mean BMC[fc] off the drug. The mean time-weighted rate of change in the fat-corrected value was +29 +/- 5 mg/cm/year on nandrolone decanoate and -5 +/- 5 mg/cm/year off nandrolone decanoate (p less than 0.001). Nandrolone decanoate produces a significant gain in forearm mineral content even after allowing for changes in forearm fat content during therapy.

Aged↗

A review of medical education and medical informatics.

Physicians have considerable difficulty collecting and interpreting information from patients, dealing with the uncertainties associated with diagnosing and treating their patients, communicating precisely with one another, keeping up to date, and applying recommended procedures when indicated. Some of the advances in information technology may help physicians to manage information more effectively through more accessible, validated clinical indexes, data bases of diagnostic test characteristics, computerized audits of clinical activities with feedback, expert systems, on-line access to the medical literature, and other tools of medical informatics. Medical educators can catalyze this process by facilitating the introduction of information technology into academic clinical settings so that students can learn its use first-hand and by promoting the evolution of this and other aspects of medical informatics, a new discipline dedicated to the solution of information problems in health care. The potential roles for computer-aided instruction and centralized computer laboratories in medical schools are much less clear.

Canada↗

The magnesium-protoporphyrin IX (oxidative) cyclase system. Studies on the mechanism and specificity of the reaction sequence.

Mg-protoporphyrin IX monomethyl ester cyclase activity was assayed in isolated developing cucumber (Cucumis sativus L. var. Beit Alpha) chloroplasts [Chereskin, Wong & Castelfranco (1982) Plant Physiol. 70, 987-993]. The presence of both 6- and 7-methyl esterase activities was detected, which permitted the use of diester porphyrins in a substrate-specificity study. It was found that: (1) the 6-methyl acrylate derivative of Mg-protoporphyrin monomethyl ester was inactive as a substrate for cyclization; (2) only one of the two enantiomers of 6-beta-hydroxy-Mg-protoporphyrin dimethyl ester had detectable activity as a substrate for the cyclase; (3) the 2-vinyl-4-ethyl-6-beta-oxopropionate derivatives of Mg-protoporphyrin mono- or di-methyl ester were approx. 4 times more active as substrates for cyclization than the corresponding divinyl forms; (4) at the level of Mg-protoporphyrin there was no difference in cyclase activity between the 4-vinyl and 4-ethyl substrates; (5) reduction of the side chain of Mg-protoporphyrin in the 2-position from a vinyl to an ethyl resulted in a partial loss of cyclase activity. This work suggests that the original scheme for cyclization proposed by Granick [(1950) Harvey Lect. 44, 220-245] should now be modified by the omission of the 6-methyl acrylate derivative of Mg-protoporphyrin monomethyl ester and the introduction of stereo-specificity at the level of the hydroxylated intermediate.

Chlorophyll↗