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Biomedical subjects

W McLean

Publications and source records attributed to W McLean.

At least 19 recordsLinked to original sources
PubMed2004

Linkage and association studies of discoidin domain receptor 1 (DDR1) single nucleotide polymorphisms (SNPs) in juvenile oligoarthritis.

OBJECTIVES: Multiple independent juvenile oligoarthritis susceptibility loci have been identified within the major histocompatibility complex (MHC), including HLA-A, HLA-DRB1 and an as yet unlocalized effect in the centromeric class I region. The discoidin domain receptor 1 (DDR1) gene resides within this region and codes for a receptor tyrosine kinase that plays an important role in regulating cell attachment to collagen, chemotaxis, proliferation and matrix metalloproteinase (MMP) production. DDR1 expression in chondrocytes has not been investigated. The objectives of this study were to investigate expression of DDR1 in healthy chondrocytes and to identify linkage and association of this candidate gene with juvenile oligoarthritis. METHODS: A set of 135 simplex juvenile idiopathic arthritis families consisting of one affected child and healthy parent(s) and 199 healthy unrelated individuals were genotyped for six single nucleotide polymorphisms (SNPs) within the DDR1 gene using the primer extension SNaPshot trade mark method. Single-point and multipoint transmission disequilibrium tests were carried out with the ETDT and TDTPHASE packages. Allele frequency comparisons between cases and controls were carried out with the chi(2) test. DDR1 expression was investigated in normal articular cartilage by RT-PCR and immunofluorescence methods. RESULTS: No linkage and association with any of the six SNPs or their haplotypic combinations were observed in the families studied. No significant differences were observed in allele frequencies between patients and controls. DDR1 expression was found in normal articular cartilage by RT-PCR and by immunofluorescence. CONCLUSIONS: The DDR1 SNPs examined are not involved in susceptibility to juvenile oligoarthritis.

Arthritis, Juvenile↗
PubMed2004

H2O outgassing from silica-filled polysiloxane TR55.

Temperature-programmed desorption/decomposition (TPD) was employed to obtain the moisture content and outgassing kinetics of TR55, a silica-filled cross-linked polysiloxane. The total moisture content of TR55 in the as-received state and after 20-30 min of vacuum pumping in the load-lock prior to TPD was measured to be on the order of 0.35 wt%. Physisorbed H(2)O and chemisorbed H(2)O account for about 13.2 and 86.8%, respectively, of the 0.35 wt% measured moisture content. H(2)O outgassing models based on the kinetics measured from TPD experiments suggest that loosely bound chemisorbed water outgasses in a dry environment slowly but continuously over many decades at or a little above room temperature. However, physisorbed water can be easily pumped out in a matter of hours at around 400 K.

Journal Article↗
PubMed2001

A double-deletion mutation in the Pitx3 gene causes arrested lens development in aphakia mice.

The recessive aphakia (ak) mouse mutant is characterized by bilateral microphthalmia due to a failure of lens morphogenesis. We fine-mapped the ak locus to the interval between D19Umi1 and D19Mit9, developed new polymorphic markers, and mapped candidate genes by construction of a BAC contig. The Pitx3 gene, known to be expressed in lens primordia, shows zero recombination with the ak mutation on our intersubspecific intercross panel representing 1170 meioses. A recent report described a deletion in the intergenic region between Gbf1 and Pitx3 as the possible ak mutation. Our results differ in that we find not only the distant intergenic deletion, but also a much larger deletion directly in the Pitx3 gene, eliminating exon 1 and extending into intron 1 and the promoter region. Pitx3 transcript levels are severely reduced in ak/ak mice from E11.5 to newborn (5 +/- 1% of the wildtype levels at E13.5), while an involvement of the flanking Gbf1 and Cig30 genes in the aberrant lens development is highly unlikely based on expression analysis. We conclude that the ak mutation consists of two deletions, the larger of which removes part of Pitx3, indicating a crucial role of this gene in early lens development.

Acetyltransferases↗
PubMed2001

The mechanism of palatal clefting in the Col11a1 mutant mouse.

The occurrence of cleft palate in mutant mice offers an opportunity to understand the possible role of specific genes in palatogenesis. Here, cleft palate in mice carrying the chondrodysplasia (cho) defect, which consists of an autosomal-recessive mutation in the collagen gene Col11a1, was investigated. The proposed cause of cleft palate in cho homozygous mice is failure of the palatal shelves to adhere and make contact due to mandibular growth abnormalities. Another cause of cleft palate that has recently been demonstrated in other animal models is failure of the midline epithelial seam forming between the shelves to undergo epithelial-mesenchymal transformation (EMT). The present strategy to test the likelihood of this second possibility was to culture the unfused cho/cho palatal shelves at different stages of development to see if they were capable of adhering and undergoing EMT in vitro. By using carboxydichlorofluorescein succinimidyl ester to trace the fate of the medial-edge epithelium (MEE), it was shown that cho/cho palates have full potential for MEE adherence and EMT up to embryonic day 17.5/18.5, when epithelia keratinize before birth, preventing the adherence of both the normal and homozygous palatal shelves. Thus, the major effect of the mutant collagen gene on the palate is likely to be via mandibular growth disruption. The possibility that unfused palatal shelves in other clinical syndromes can adhere and undergo EMT if brought into contact at appropriate times before birth has important therapeutic implications.

Animals↗
PubMed2001

Mouse models of abnormal skeletal development and homeostasis.

Studies of a number of mouse mutations with skeletal defects have contributed significantly to the understanding of bone development and homeostasis. In many cases, such mutants are also genetic models of disorders in humans, characterized by reduced bone mass (osteoporosis), increased bone mass (osteopetrosis), or abnormalities in endochondral ossification (chondrodysplasias).

Animals↗
PubMed2000

Is there an indication for the use of barbiturate-containing analgesic agents in the treatment of pain? Guidelines for their safe use and withdrawal management. Canadian Pharmacists Association.

OBJECTIVE: To provide medical and pharmaceutical practitioners with information on the effectiveness, safety and risks associated with barbiturate-containing analgesic (BCA) agents and an approach to management of withdrawal from BCAs. METHODS: The benefits of using BCAs in the treatment of pain (compared with using non-BCAs) were weighed against potential risks. The procedures for discontinuation of BCAs in patients with pain were considered, and evidence showing that BCAs constitute a public health risk was reviewed. The evidence serving as the basis for the clinical guidelines was compiled from a number of sources, including key papers in the field, published and unpublished papers, and reports by Addiction Research Foundation researchers, a MEDLINE search from 1967 to November 1996, and communication with Canadian manufacturers of BCAs. RESULTS: There is no evidence that there is a clinically important enhancement of analgesic efficacy of BCAs due to the barbiturate constituent. No epidemiological studies on the relative frequency of abuse and dependence, or studies that have analyzed combination product use from a public health and social benefit to risk perspective, have been published to clarify the issues about the nature, extent and seriousness of these problems. RECOMMENDATIONS: No evidence exists to show a clinically important enhancement of analgesic efficacy of BCAs due to the barbiturate constituents. Because BCAs do not have a therapeutic advantage, there is no clinical reason to choose such a combination product when a simpler and often less expensive analgesic formulation (eg, acetaminophen, acetylsalicylic acid, nonsteroidal anti-inflammatory drug or narcotic) or a more specific anti-migraine drug (eg, dihydroergotamine or sumatriptan) is available. BCAs should be avoided in elderly people and should not be used in children. Extrapolation from published reports on abuse and withdrawal syndrome with these drugs suggests that BCAs have the potential to produce drug dependence and addictive behaviour, especially with regular use. In BCA overdose, the barbiturate component is only one of the clinically significant contributors to any morbidity, but its presence can complicate the management of additive or synergistic toxicities. Therefore, there is no reason to choose a combination product when a simpler product may be a safer alternative by minimizing the potential for addiction and the occurrence of additive side effects or toxicities. It is further recommended that prescribers re-evaluate treatment for patients using BCAs. Recommendations for withdrawal are provided, based on estimated consumption.

Analgesics↗
PubMed1997

Risks associated with occupational glass injury in bar staff with special consideration of hepatitis B infection.

Since bar workers often sustain cuts from unwashed bar glasses, the aims of this study were to investigate risk of injury and to examine the sero-prevalence of markers for hepatitis B amongst bar staff. Ninety-one bar staff recruited by newspaper advertisement were asked about injury experience and life-style risks associated with transmission of hepatitis B and were tested for hepatitis B surface antigen (HBsAg) and core antibody (anti-HBc). Seventy-four per cent reported lacerations from broken glassware at work: 18% had sustained such injuries in more than 10 incidents. Fifty-five per cent of respondents reported occupational skin contact with body fluids. Anti-HBc prevalence for the study group was 1.1%, suggesting that bar staff were not at increased risk from hepatitis B infection. Although 30% wore gloves for high-risk tasks, there was no evidence that glove wearing prevented glass lacerations. This level of injury experience and exposure to body fluids is unacceptable and represents a potential risk of cross-infection. Hepatitis B immunization should be considered in this group. Urgent action, including the replacement, wherever possible, of annealed with tempered bar-glassware, is necessary to protect bar workers from glass injury.

Accidents, Occupational↗
PubMed1996

A comparison between phosphors for aviator's night vision imaging system.

BACKGROUND: The visual display on night vision goggles (NVG's) is green and isochromatic (P22 phosphor). Future systems are expected to use a P43 phosphor which has a narrower visible spectrum and is yellowish green, while the P22 is deeper green. In transitioning to the P43, some NVG's may have P22 and P43 phosphors paired in the same NVG. The purpose of this study was to evaluate the suitability of the P43 phosphor and the effect of mixing phosphors in the same NVG. METHODS: We tested three systems: one with P22 phosphors in both tubes (P22), one with P43 in both tubes (P43), and one with P22 in the right and P43 in the left tube (mixed). Visual acuity (VA), contrast sensitivity (CS), flicker sensitivity, and dynamic CS were measured in six subjects with measures repeated across the three systems (P22, P43 and mixed). RESULTS: There was no difference between systems in VA or CS across a range of simulated night sky conditions. There also was no difference between systems in sensitivity to flicker. Performance on dynamic CS was slightly better with the P43 display, which may relate to the faster decay time of this phosphor. CONCLUSIONS: These results provide no contraindication for using the P43 phosphor in NVG's (paired or unpaired), but it would be prudent to minimize mixing of phosphors in the same NVG. Additional factors that may affect performance with different color displays are discussed.

Adult↗
PubMed1994

A regional pharmacokinetic consultation service.

Clinical pharmacokinetics represents a way to ensure that a patient is receiving an optimal dose of a given drug for a specific indication. Pharmacokinetic consultation services have been implemented in many teaching hospitals and tertiary care facilities in the past. This project evaluated the feasibility of expanding the process to several community hospitals with one coordinator. Twenty-seven hospitals, members of the Ottawa Valley Regional Drug Information Service, were approached. Fifty-two pharmacists from 21 sites agreed to participate. Four modules were taught: basic principles, theophylline, aminoglycosides, and digoxin. Regular follow-up meetings were arranged so pharmacists from different hospitals could share their administrative and patient-specific problems and solutions. After two years, 16 departments have implemented a clinical pharmacokinetic service and monitor 82% of targeted drug levels. The pharmacists trained in clinical pharmacokinetics through the project recommended changes in the regimen in 45% of all their consultations. Eight-one percent of these were accepted and implemented by physicians. These results indicate that pharmacists from small community hospitals can be trained by one individual to provide clinical pharmacokinetic services with minimal supervision. It also shows that these hospitals have a need for such services.

Aminoglycosides↗
PubMed1993

How security is changing at John Hopkins.

William McLean, CHPA, is security director at Johns Hopkins Medical Institutions, Baltimore, MD. Formerly chief of security with the Baltimore City Department of Hospitals, McLean has worked in health care security at the director level for 15 years. He also spent eight years with the Baltimore City Police Department. At Hopkins, officials recently decided to overhaul the $7 million security operation because of increasing crime. In this interview, McLean talks about some of the changes.

Baltimore↗
PubMed1989

The history of a comprehensive pharmacokinetic service.

This paper reviews the 10 years of providing a Clinical Pharmacokinetic Service (CPS) at the Ottawa General Hospital. The history of the service is followed from the early days of selective monitoring of two drugs to the present comprehensive level of monitoring of essentially all drug concentrations analyzed in the hospital. The administrative development is presented, including that of the Subcommittee on Pharmacokinetics. A justification study is described, the results of which indicated 92 percent acceptance of the CPS' recommendations. An effort to withdraw service for digoxin was unsuccessful in that a concurrent study indicated a deterioration in the appropriateness of digoxin prescribing. Several quality assurance techniques are discussed, including a recent audit on predictability. Finally, the education and research links are summarized. Based on the experience of the authors, it is concluded that a comprehensive CPS is an indispensable clinical service.

Digoxin↗
PubMed1987

Digoxin-like immunoreactive substance (DLIS) in liver disease: comparison of clinical and laboratory parameters in patients with and without DLIS.

Falsely elevated serum digoxin values have recently been reported in patients with liver disease. Since not all patients have circulatory digoxin-like immunoreactive substance (DLIS) in their serum, we compared the clinical and laboratory findings in patients with and without DLIS. Thirty-two patients with liver disease were studied. The only parameter that was significantly different in the two groups was serum bilirubin. In the group of patients with DLIS, significant correlations were obtained between DLIS and bilirubin and DLIS and creatinine. We postulate that increased levels of DLIS in serum are due to an abnormality of DLIS excretion.

Adult↗