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Biomedical subjects

G McDonnell

Publications and source records attributed to G McDonnell.

At least 19 recordsLinked to original sources

Haplotype analysis of the preprotachykinin-1 (TAC1) gene in multiple sclerosis.

The potential relevance of chromosome 7q21-22 in susceptibility to multiple sclerosis (MS) has been highlighted in genome-wide linkage screens as well as in association studies of 7q-specific polymorphic microsatellites. Especially, recent, independently performed studies have provided evidence for significant association of the markers D7S554 and D7S3126 with MS in Sardinian, Northern Irish and Spanish-American cohorts. The gene most closely located to these markers is the neuropeptide preprotachykinin-1 (TAC1) gene. Both its position and the array of biological functions exerted by its expression products make it a logical primary choice for further scrutiny as the putative chromosome 7q21-22 MS susceptibility gene. We report identification of eight polymorphisms in this gene by means of a sequencing approach. A Northern Irish case-control was typed for six of these polymorphisms. One of these, an intron 1 single-nucleotide polymorphism (SNP), showed significant association with MS (P=0.009). Two-marker haplotypes composed of allelic combinations of TAC1 promoter-intron 1 SNPs were highly significantly associated with MS and more so with the relapsing-remitting form of this disease. While independent reproduction of these data in other data sets is indicated, our work is suggestive for a role of the TAC1 gene in MS. Genes and Immunity (2005) 6, 265-270. doi:10.1038/sj.gene.6364175 Published online 24 February 2005.

Genetic Predisposition to Disease↗

Decontamination with vaporized hydrogen peroxide is effective against Mycobacterium tuberculosis.

AIMS: To determine the efficacy of room fumigation with vaporized hydrogen peroxide (VHP) in decontamination of viable Mycobacterium tuberculosis. METHODS AND RESULTS: About 8 x 10(4)-2.3 x 10(6) CFU of M. tuberculosis H37Rv and M. tuberculosis Beijing were dried in 10-microl drops in tissue culture plates, placed in steam-permeable Tyvek pouches and distributed on laboratory surfaces. The room was exposed to VHP delivered by air conditioning. Different exposure conditions were tested. Exposure to VHP resulted in sterilization of the bacterial samples in three different test runs. CONCLUSIONS: VHP treatment is an effective means of reducing and eliminating room contaminations of M. tuberculosis. SIGNIFICANCE AND IMPACT OF THE STUDY: Fumigation with VHP represents an alternative to formaldehyde fumigation, particularly for decontamination of animal rooms in tuberculosis research laboratories.

Anti-Bacterial Agents↗

Polymorphisms in the interleukin-4 and IL-4 receptor genes and multiple sclerosis: a study in Spanish-Basque, Northern Irish and Belgian populations.

Cytokine gene polymorphisms are known to influence susceptibility and disease course of many autoimmune diseases. Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system white matter characterized by inflammation, demyelination and axonal damage. We analysed both the well-known intronic variable number of tandem repeat (VNTR) and +33 C/T single-nucleotide polymorphisms (SNP) in the IL-4 gene, as well as the functional Q551R SNP in the IL4-R gene in a cohort of three distinct populations comprising sporadic cases and controls from the northern Spanish Basque Country and Northern Ireland, as well as family trios from Belgium. The IL-4 +33 TT genotype was decreased in primary progressive (PP) versus relapsing-remitting (RR) patients in the Northern Irish population (OR = 0.14; 95% CI = 0.018-1.09). Two-marker haplotype distribution of the VNTR and +33 C/T SNP in PP patients differed from that seen in RR patients in Northern Ireland (P = 0.03). The R allele of the Q551R SNP was significantly under-transmitted in the Belgian trio families (P = 0.003), although this effect was not seen in the Northern Irish and Basque data sets. We did not identify IL-4-IL4-R gene-gene interaction in determining susceptibility or clinical parameters of MS. Disease or genetic heterogeneity or both may be responsible for the observed lack of reproduction in different populations. Our data reinforce recent findings for a role of IL4-R in susceptibility to MS.

Adult↗

Biodecontamination of animal rooms and heat-sensitive equipment with vaporized hydrogen peroxide.

Common methods used to decontaminate and disinfect laboratory animal areas are difficult to standardize, labor-intensive, and potentially hazardous for staff members and the environment. As an alternative to traditional methods, we tested fumigation with vaporized hydrogen peroxide by using the VHP 1000 Biodecontamination System. The design of our air-conditioning system allowed the connection of the generator to any animal room by using the ventilation piping, thus forming a closed circuit. A 3-h cycle consisting of dehumidification, conditioning, sterilization, and aeration was developed and shown to be effective. The biodecontamination process was monitored during five independent trials using chemical and biological (Bacillus stearothermophilus spores) indicators. Contact plates for testing surfaces and room air for environmental bacteria, yeasts, and fungi consistently showed fewer than 10 colony-forming units per 100 cm2 or per 1 liter air. In addition, this method proved successful with heat-sensitive equipment like the blower units of individually ventilated caging systems. Overall, the system was easy to use and very effective in biodecontaminating animal rooms and equipment in a reproducible manner. There were no signs of corrosion or functional damage after more than 10 fumigation cycles. Work load and potential health risk for staff members and the environment was negligible.

Animals↗

Clinical correlation of a skin antisepsis model.

The use of pigskin as a test substrate for evaluating topical antimicrobial activity has been developed. Simulated handwashing protocols with this in vitro model in parallel with in vivo studies have been evaluated, based on an ASTM method for the clinical evaluation of a healthcare personnel handwash. Using Serratia marcescens as the test organism, similar log reductions were observed using the in vitro model when compared to in vivo efficacy. Results suggest that this model can be used as a reliable indicator of antiseptic efficacy on the skin. The use of sterilized skin simplifies the use of this model for both efficacy and skin-pathogen interaction studies.

Adolescent↗

Antiseptics and disinfectants: activity, action, and resistance.

Antiseptics and disinfectants are extensively used in hospitals and other health care settings for a variety of topical and hard-surface applications. A wide variety of active chemical agents (biocides) are found in these products, many of which have been used for hundreds of years, including alcohols, phenols, iodine, and chlorine. Most of these active agents demonstrate broad-spectrum antimicrobial activity; however, little is known about the mode of action of these agents in comparison to antibiotics. This review considers what is known about the mode of action and spectrum of activity of antiseptics and disinfectants. The widespread use of these products has prompted some speculation on the development of microbial resistance, in particular whether antibiotic resistance is induced by antiseptics or disinfectants. Known mechanisms of microbial resistance (both intrinsic and acquired) to biocides are reviewed, with emphasis on the clinical implications of these reports.

Anti-Infective Agents, Local↗

Behavioural response home monitoring of good and insomniac sleepers.

Can the fundamental differences in sleep structure known to differentiate good from insomniac sleepers (e.g., sleep length, sleep onset latency [SOL], number of sleep disruptions, etc.) be identified using a behavioural sleep/wake (S/W) monitor in the home? Sixteen women (8 good and 8 insomniac sleepers) enrolled in an introductory psychology course participated in a study of S/W patterns. They used a portable version of the Ogilvie and Wilkinson (1988) behavioural response (BR) system in their homes for 4 consecutive nights. Insomniacs had greater SOLs, less efficient sleep, and tended to have a greater number of arousals as compared with good sleepers. The data indicate that the behavioural system could be used as a diagnostic tool for in-home evaluations of disorders of initiating and maintaining sleep.

Adult↗

The clinical spectrum of staphylococcal bacteraemia: a review of 101 Melanesian patients from Papua New Guinea.

The clinical features of 101 Melanesian patients with Staphylococcus aureus bacteraemia observed during two 2-year periods (1977-1979 and 1985-1987) in a university teaching hospital in Papua New Guinea are reviewed. The age of the patients ranged from 12 to 70 years. There were 69 males and 32 females. Diabetes mellitus, found in 15 patients, was the most common predisposing factor. Most of the patients (87%) had community-acquired infection. Soft-tissue infection, pneumonia, arthritis, osteomyelitis, intravenous-site thrombophlebitis, cerebral abscess, endocarditis and cavernous sinus thrombosis were among the clinical entities observed. Soft tissues and lungs were the most common sites of primary and secondary foci of infection, respectively. All but 1 of the 101 blood isolates were resistant to penicillin G and none was resistant to methicillin. The overall case fatality rate was 24%. These data demonstrate that staphylococcal bacteraemia in adult Papua New Guineans is mostly community acquired and has a high mortality. Skin and soft tissues are the major primary foci of infection leading to staphylococcal bacteraemia.

Adolescent↗

Effect of heparin concentration and infusion rate on the patency of arterial catheters.

In a prospective randomized controlled trial involving 470 arterial catheters in 470 children, we studied the effect of changing either the concentration or the flow rate of a heparin infusion. Although catheters tended to remain patent longer with a flow rate of 2 ml/h rather than 1 ml/h, the difference was not statistically significant. Increasing the heparin concentration from 1 to 5 U/ml significantly prolonged catheter patency.

Arteries↗

Hematogenous staphylococcal pneumonia secondary to soft tissue infection.

Staphylococcal pneumonia is rare, has a high mortality and morbidity rate, and occurs commonly during influenza epidemics (airborne) or during the course of right sided bacterial endocarditis in drug addicts (blood borne). In recent years, much emphasis has been given to the staphylococcal infections in intravenous drug abusers. This report describes ten patients with staphylococcal pneumonia resulting from soft tissue infection who were previously healthy and had no history of drug abuse. They were 12 to 45 years old. Eight were male patients. Soft tissue infection was community-acquired in nine and was most commonly located in the lower extremities. Three patients had diabetes. All presented with a clinical picture of acute pneumonia. Hemoptysis occurred in three. Chest roentgenogram showed multiple large or small round discrete densities in most of the patients. Lobar involvement was notably absent. Eight developed cavitary lesions in their lungs. The average length of hospital stay was 40 days. One patient died and six developed complications. Staphylococcal etiology should be suspected in patients with acute pneumonia who have soft tissue infection or have characteristic chest roentgenogram findings; antistaphylococcal agents should be included in the therapeutic regimens of such patients until the results of the cultures are known.

Adolescent↗

Interaction of disinfectant residues on cleanroom substrates.

This study will determine the levels of disinfectant residues on stainless steel surfaces after simulated manual cleaning activities. Additionally, this study will determine if chemical interactions between different chemical agents, representative of commonly used cleanroom disinfectant technologies, subsequently applied to the same surfaces exist, and to what degree these interactions impact sporicidal performance of an oxidizing biocide against Bacillus subtilis.

Bacillus subtilis↗