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Biomedical subjects

Michael Wilson

Publications and source records attributed to Michael Wilson.

At least 19 recordsLinked to original sources

Oral bacteria resistant to mercury and to antibiotics are present in children with no previous exposure to amalgam restorative materials.

Dental plaque from 76 children without amalgam restorations was screened for bacteria resistant to mercuric chloride. Seventy-one per cent of the children harboured mercury-resistant oral bacteria and the median percentage of the total oral microflora resistant to mercuric chloride was 0.007% (range 0-5.3%). Eighty-seven mercury-resistant bacteria were isolated and 86% of these were streptococci with Streptococcus mitis predominating. Sixty per cent of the mercury-resistant isolates were also resistant to at least one of the four antibiotics tested (penicillin, ampicillin, erythromycin and tetracycline) with resistance to tetracycline (40% of isolates) most frequently encountered.

Anti-Bacterial Agents↗

Identification of a novel lipase gene mutated in lpd mice with hypertriglyceridemia and associated with dyslipidemia in humans.

Triglyceride (TG) metabolism is crucial for whole body and local energy homeostasis and accumulating evidence suggests an independent association between plasma TG concentration and increased atherosclerosis risk. We previously generated a mouse insertional mutation lpd (lipid defect) whose phenotype included elevated plasma TG and hepatic steatosis. Using shotgun sequencing (approximately 500 kb) and bioinformatics, we have now identified a novel lipase gene lpdl (lpd lipase) within the lpd locus, and demonstrate the genetic disruption of exon 10 of lpdl in the lpd mutant locus. lpdl is highly expressed in the testis and weakly expressed in the liver of 2-week old mice. Human LPDL cDNA was subsequently cloned, and was found to encode a 460AA protein with 71% protein sequence identity to mouse lpdl and approximately 35% identity to other known lipases. We next sequenced the human LPDL gene exons in hypertriglyceridemic subjects and normal controls, and identified seven SNPs within the gene exons and six SNPs in the adjacent introns. Two hypertriglyceridemic subjects were heterozygous for a rare DNA variant, namely 164G>A (C55Y), which was absent from 600 normal chromosomes. Two other coding SNPs were associated with variation in plasma HDL cholesterol in independent normolipidemic populations. Using bioinformatics, we identified another novel lipase designated LPDLR (for 'LPDL related lipase'), which had 44% protein sequence identity with LPDL. Together with the phospholipase gene PSPLA1, LPDL and LPDLR form a new lipase gene subfamily, which is characterized by shortened lid motif. Study of this lipase subfamily may identify novel molecular mechanisms for plasma and/or tissue TG metabolism.

Amino Acid Sequence↗

Diagnosis and monitoring of hemorrhagic shock during the initial resuscitation of multiple trauma patients: a review.

The initial management of the multiple trauma victim requires evaluation for potential hemorrhage and ongoing monitoring to assess the efficacy of resuscitation and avoid complications related to hemorrhagic shock. A variety of strategies exist to assess circulatory status, including hemodynamic monitoring, tissue perfusion measurement, and use of serum markers of metabolism. We review available technologies used to assess fluid status and tissue perfusion in patients with blood loss or hemorrhagic shock, discuss how these methods can be used effectively and efficiently during initial trauma resuscitation to guide therapy and disposition, and suggest directions for future research to improve outcomes by providing more appropriate and timely care and avoiding unnecessary complications.

Biomarkers↗

The application of the precautionary principle to the blood system: the Canadian blood system's vCJD donor deferral policy.

The precautionary principle is an influential concept that has been widely used in international treaties and declarations involving the protection of the environment. The principle is now being applied to the development of transfusion policy. In this article, we examine the application of the precautionary principle in the policy process leading to Canada's decision to defer donations from individuals who had traveled to the United Kingdom because of concerns over variant Creutzfeldt-Jakob disease. We found that, although the principle prominently influenced the decision-making process, problems existed with its interpretation. In particular, there was difficulty in balancing the risk prevented by applying a precautionary measure against the risk introduced by the same measure; in this case, the potential for shortages of blood. This dilemma is somewhat unique to the public health sector and will likely recur in future applications of the principle to transfusion policy.

Blood Banks↗

Effect of restoration of children's teeth with mercury amalgam on the prevalence of mercury- and antibiotic-resistant oral bacteria.

The purpose of this study was to determine whether placement of mercury amalgam restorations in children's teeth induces an increase in oral bacteria resistant to mercury, penicillin, ampicillin, erythromycin, or tetracycline. Dental plaque and saliva samples from 16 children without mercury amalgam restorations were screened for bacteria resistant to mercury or to one of the antibiotics prior to, and 1 month after, placement of the amalgam restoration. Following amalgam placement, there was no significant increase in the number of children harboring bacteria resistant to mercury, penicillin, ampicillin, erythromycin, or tetracycline; neither was there an increase in the proportions of such organisms. This study has shown that the presence of mercury restorations in children's teeth has little effect on the prevalence of mercury- or antibiotic-resistant oral bacteria.

Adolescent↗

Olanzapine versus placebo in acute mania: treatment responses in subgroups.

Two double-blind, placebo-controlled trials of olanzapine in acute mania showed significant overall antimanic efficacy, based on reductions in mania ratings. Their subject-level data were pooled to increase statistical power to test for differences in treatment responses among 10 subgroup pairs of interest using generalized estimating equations methods. Similar drug/placebo superiority and responsiveness to olanzapine was found in men versus women, psychotic versus nonpsychotic subjects, and those presenting in mania versus mixed states, and responses were independent of onset age, current age, or prior illness based on episodes, hospitalizations, recent rapid cycling, lifetime substance use, or previous antipsychotic treatment. Olanzapine and placebo responses paralleled closely (r(s) = 0.73). Patients were relatively more responsive to olanzapine who were younger at illness onset, lacked prior substance abuse, and had not previously received antipsychotic treatment (efficacy ratios 1.5-1.7, all P < 0.01). These well-powered comparisons of subgroups of interest indicate broad efficacy of olanzapine in the treatment of acute mania.

Acute Disease↗

Achilles tendon ruptures: functional outcome of surgical repair with a "pull-out" wire.

This is a retrospective review of 30 consecutive patients with acute Achilles tendon ruptures treated surgically by a single surgeon between 1992 and 1999. Repair was effected with a 26-gauge "pull-out" wire technique. A compressive dressing reinforced with plaster was employed to immobilize the ankle in neutral for 6 weeks. The hardware was removed 6 weeks postoperatively under local anesthesia. Intensive physical therapy was employed until ankle motion was symmetric and single heel raise was possible. Average follow-up was 4 years (range, 1-8 years). Nearly all patients (29/30) report satisfaction with their outcome. Most patients (29/30) had AOFAS Ankle-Hindfoot Scores greater than 90. Twenty-three (77%) returned to preoperative levels of athletic activities. Isometric testing documented 81% plantarflexion strength compared to the normal ankle at a mean of 32 months postoperatively. Five of eight women reported shoe wear difficulties related to the incision. There were no reruptures or deep infections. The "pull-out" wire technique is recommended for patients who wish to return to an active lifestyle. This method provides rigid approximation of tendon length, minimizes strangulation of tissue, repairs large gaps, and avoids late foreign-body reactions.

Achilles Tendon↗

In vitro assessment of the plaque-removing ability of hydrodynamic shear forces produced beyond the bristles by 2 electric toothbrushes.

BACKGROUND: The aim of this study was to compare the efficacy of interproximal plaque removal by the hydrodynamic shear forces produced by 2 electric toothbrushes (toothbrush A, Sonicare Plus and toothbrush B, Braun Oral B) using laboratory-grown plaque biofilms in an anatomically correct in vitro brushing model. METHODS: In vitro oral biofilms were grown in a constant-depth film fermenter on hydroxyapatite (HA) discs. Brushing experiments were conducted in a specially constructed machine designed to simulate the brushing of interproximal plaque between mandibular molar teeth; the bristles of the toothbrush did not make contact with the biofilm at any time. The load force between the brushes and teeth were in accordance with typical use and an exposure time of 5 seconds was used throughout. The efficacy of brushing was assessed by enumeration of the percentage of viable bacteria removed from the HA discs. These experiments were conducted with the electronic effect of the toothbrushes either activated or inactivated. RESULTS: Activation of toothbrush A significantly (P = 0.004) increased the median percentage of bacteria removed from 0.47% to 48.45%. Likewise, activation of toothbrush B significantly (P = 0.015) increased the median percentage of bacteria removed from 2.85% to 15.86%. The median percentage of plaque bacteria removed by the active toothbrush A was significantly (P = 0.009) greater than that removed by toothbrush B in this model system. CONCLUSION: These data imply that toothbrush A would be more effective than toothbrush B at removing interproximal dental plaque in vivo.

Adult↗

Oral health in children with chronic renal failure.

Seventy children with chronic renal failure (CRF) aged 4-13.6 years were recruited from the Renal Unit of the Great Ormond Street Hospital for Children. Indices were recorded for dental caries, dental plaque, gingival inflammation, gingival enlargement, and enamel defects. Salivary urea, buffering capacity, and the oral streptococcal flora were determined for 25 of the children. A significantly greater proportion of the CRF children was caries free, 40% compared with 8.5% of the controls. The mean plaque score was significantly greater in the CRF group for both the primary 12.7 (16) and permanent dentition 22.0 (18.2) compared with the controls, 5.3 (7.6) and 15.5 (13.3), respectively. Eight CRF children had gingival enlargement. Enamel defects affecting the permanent teeth were observed in 57% of the CRF children compared with 33% of the controls. The buffering capacity was significantly greater in the CRF group, pH 6.4 (0.5) compared with the controls pH 5.6 (0.8). The mean salivary urea level (mmol/l) was significantly greater in the CRF children, 11.6 (5.9) compared with 3.6 (1.4) for the controls. The isolation frequency of Streptococcus mutans was significantly greater from controls compared with the CRF children ( P=0.002). An integrated dental service needs to be developed with emphasis on tooth brushing to prevent gingival hyperplasia and periodontal disease after puberty.

Adolescent↗

Epistatic interaction between KIR3DS1 and HLA-B delays the progression to AIDS.

Natural killer (NK) cells provide defense in the early stages of the innate immune response against viral infections by producing cytokines and causing cytotoxicity. The killer immunoglobulin-like receptors (KIRs) on NK cells regulate the inhibition and activation of NK-cell responses through recognition of human leukocyte antigen (HLA) class I molecules on target cells KIR and HLA loci are both highly polymorphic, and some HLA class I products bind and trigger cell-surface receptors specified by KIR genes. Here we report that the activating KIR allele KIR3DS1, in combination with HLA-B alleles that encode molecules with isoleucine at position 80 (HLA-B Bw4-80Ile), is associated with delayed progression to AIDS in individuals infected with human immunodeficiency virus type 1 (HIV-1). In the absence of KIR3DS1, the HLA-B Bw4-80Ile allele was not associated with any of the AIDS outcomes measured. By contrast, in the absence of HLA-B Bw4-80Ile alleles, KIR3DS1 was significantly associated with more rapid progression to AIDS. These observations are strongly suggestive of a model involving an epistatic interaction between the two loci. The strongest synergistic effect of these loci was on progression to depletion of CD4(+) T cells, which suggests that a protective response of NK cells involving KIR3DS1 and its HLA class I ligands begins soon after HIV-1 infection.

Acquired Immunodeficiency Syndrome↗

Oral bacteria in multi-species biofilms can be killed by red light in the presence of toluidine blue.

BACKGROUND AND OBJECTIVES: Oral bacteria can be killed by light in the presence of a suitable photosensitizer, and this could be used in the treatment of oral infections. In these diseases, however, bacteria are present as biofilms, which are refractive to antimicrobial agents. The purpose of this study was to determine whether oral bacterial biofilms were susceptible to lethal photosensitization. STUDY DESIGN/MATERIALS AND METHODS: Multi-species biofilms of oral bacteria were irradiated with light from a helium/neon laser in the presence of toluidine blue O (TBO) and the survivors enumerated. Controls examining the effects of light and TBO alone were also included. The biofilms were also examined by confocal scanning laser microscopy (CSLM). RESULTS: CSLM revealed that the biofilms had structures similar to those of dental plaque. Although, the biofilms consisted of extremely large numbers of bacteria ( approximately 9 x 10(9)), 97.4% were killed following irradiation with 31.5 J of laser light in the presence of 25 microg/ml TBO. CONCLUSIONS: Substantial numbers of oral bacteria in multi-species biofilms can be killed by light in the presence of TBO. This may be useful in the treatment of dental plaque-related diseases.

Adult↗

Streptococcus sanguis secretes CD14-binding proteins that stimulate cytokine synthesis: a clue to the pathogenesis of infective (bacterial) endocarditis?

Streptococcus sanguis is the major causative organism of infective (bacterial) endocarditis but, surprisingly, almost nothing is known about how it induces endocardial inflammation. In earlier studies we have shown that many bacteria secrete potent cytokine-inducing or -inhibiting proteins. We have therefore isolated the material secreted by S. sanguis grown on blood agar or in broth culture and have tested its ability to induce human peripheral blood monocytes to synthesize pro-inflammatory cytokines. The activation of monocytes by the secreted components of S. sanguis was almost totally blocked by heat and trypsin treatment but not by the lipopolysaccharide-inactivating antibiotic, polymyxin B, suggesting that activity is due to secreted proteins. The activity of the secreted material was significantly reduced by anti-CD14 monoclonal antibodies suggesting that the active protein (or proteins) was binding to the CD14/Toll-like receptor (TLR)4 complex. Fractionation of the secreted proteins by high performance liquid chromatography (HPLC) identified two proteins as being responsible for the majority of the cytokine induction: a manganese-dependent superoxide dismutase and a 190 kDa protein, which could not be sequenced, but which was neither CshA nor the PI/II proteins. These proteins, or the receptors to which they bind, may be therapeutic targets and may allow the development of adjunctive therapies to prevent endocardial damage during the often prolonged treatment of infective endocarditis with antibiotics. In addition, blocking of CD14 may have some therapeutic benefit.

Anti-Bacterial Agents↗

Exposure of Porphyromonas gingivalis to red light in the presence of the light-activated antimicrobial agent toluidine blue decreases membrane fluidity.

Porphyromonas gingivalis, one of the etiological agents of periodontitis, can be killed by red light in the presence of toluidine blue. The purpose of this study was to determine whether this light-induced killing was accompanied by changes in the fluidity of the organism's cytoplasmic membrane. A suspension of the organism was exposed to red light in the presence of toluidine blue, and the membrane fluidity was monitored spectrofluorimetrically by using the membrane probe trimethylammonium diphenyl hexatriene. The fluidity of the organism's cytoplasmic membrane was found to decrease significantly during lethal photosensitization, and this was accompanied by membrane condensation and vacuolation of the cells. Although changes in membrane fluidity are often attributable to lipid peroxidation, malonaldehyde (a product of lipid peroxidation) was not detectable. The disruption of membrane functions associated with a decreased membrane fluidity may contribute to the bactericidal effect of light-activated toluidine blue.

Cell Membrane↗

Effect of medium composition on the susceptibility of oral streptococci to mercuric chloride.

Although there is considerable interest in identifying mercury-resistant bacteria, no standardized assay exists for this purpose. In this study, the effect of the composition of the medium on the susceptibility of oral streptococci to HgCl(2) was investigated. The minimum inhibitory concentration (MIC) of HgCl(2) for 52 streptococcal strains and the reproducibility of MIC values for Hg-sensitive and Hg-resistant strains was determined with 11 different media. Addition of blood increased the MIC values, and some media (tryptone soya agar, with or without blood) could not discriminate between Hg-sensitive and Hg-resistant strains. The proportion of streptococci that appeared to be resistant to Hg was very high (>70%) on some media (mitis-salivarius, tryptone soya, Columbia), but not on others (Mueller-Hinton, Brain Heart Infusion, Isosensitest). The MICs of the control strains varied considerably on different testing occasions for tryptone soya agar (with and without blood), Isosensitest agar, and Columbia agar (with blood). Mueller-Hinton (without blood) appeared to be the most suitable medium for isolating Hg-resistant oral streptococci.

Agar↗

Integration of blastocyst transfer for all patients.

OBJECTIVE: To evaluate the efficacy of using day-5 embryo transfer (ET) for all patients. DESIGN: Retrospective, non-randomized comparison of day-3 ET versus day-5 ET. SETTING: Private practice. PATIENT(S): Women having in vitro fertilization and receiving either day-3 ET or day-5 ET. INTERVENTION(S): Extended embryo culture through embryonic genome activation to select those embryos with higher implantation potential. MAIN OUTCOME MEASURE(S): The following parameters were compared for day-3 ET and day-5 ET: clinical and ongoing pregnancy rates, implantation rates, patients having cryopreservation, and liveborn rates. RESULT(S): Blastocyst embryo transfer (day-5 ET) increased the clinical and ongoing pregnancy rate for patients <35 years of age and for the total program. The risk of high order multiple pregnancy was reduced by a decrease in the number of embryos transferred (2.0 vs. 2.7; day-5 ET vs. day-3 ET, respectively). However, the multiple pregnancy rate was not different due to an increase in the implantation rate (day-5 ET 43% vs. day-3 ET 27%). There was no difference in the percent of patients not having an ET (day-5 ET 2.8%; day-3 ET 1.3%). CONCLUSION(S): Blastocyst ET increased the clinical and ongoing pregnancy rate for patients <35 years of age and for the total program, with a concomitant decrease in the number of embryos transferred. However, the decrease in the number of embryos transferred did not decrease the multiple rate, but did reduce the incidence of high order multiples. Most patients (97%) had an embryo transfer. Therefore, culturing embryos an additional 48 hours through embryonic genome activation allows for selection of the most viable embryos without compromising the patient's opportunity to become pregnant.

Adult↗

Monitoring gaseous exchange: implications for nursing care.

The purpose of this study is to examine whether a relationship exists between arterial and end-tidal carbon dioxide tension (PaCO2 and PETCO2 respectively) in patients admitted to intensive care units (ICUs), and what the implications it has for nursing care. PaCO2 and PETCO2 are indicators of ventilatory adequacy which is an important aspect of respiratory function. These measures of carbon dioxide tension are obtained via invasive and non-invasive monitoring tools. Measurement of PETCO2 has only recently been introduced into ICUs and its usefulness in these environments is open to debate. A population of 30 intubated patients had 214 simultaneous measurements of PaCO2 and PETCO2 taken over a period of 10 months. The findings indicate that, despite strong significant correlations, PETCO2 cannot be used safely as a substitute for PaCO2 as the arterial/end-tidal carbon dioxide gradient is not constant, nor does capnography provide a consistently reliable indicator of PaCO2.

Adult↗

Reversal of chronic cyclosporine nephrotoxicity after heart transplantation-potential role of mycophenolate mofetil.

BACKGROUND: Chronic cyclosporine nephrotoxicity (CCN) after heart transplantation is a progressive condition that may lead to end-stage renal failure. The extent to which CCN is reversible with reduction or withdrawal of cyclosporine therapy is unknown. The aim of this study was to assess the reversibility of CCN and to assess the safety and efficacy of a strategy of cyclosporine dosage reduction, combined with conversion from azathioprine to mycophenolate mofetil (AZA/MMF switch) to maintain immunosuppression. METHODS: An AZA/MMF switch followed by cyclosporine dose reduction was undertaken in 30 heart transplant recipients (23 men, 7 women; mean age, 54 +/- 2 years) with established CCN at a mean of 90 +/- 9 months after transplantation (range, 17-182 months). The mean maintenance MMF dosage was 2.3 +/- 0.1 g/day (n = 28). Mean cyclosporine dosage was decreased from 2.3 +/- 0.2 mg/kg/day before AZA/MMF switch to 1.6 +/- 0.2 mg/kg/day. RESULTS: Three patients (10%) were withdrawn from MMF, 2 because of diarrhea and the third because of severe pneumonia that developed within 2 weeks of AZA/MMF switch. All 3 were restabilized with AZA. One patient (4%) experienced acute rejection 7 months after AZA/MMF switch. This resolved after an oral pulse of prednisolone. Systemic infections occurred in 6 patients within 12 months of AZA/MMF switch. Actuarial survival 1 year after AZA/MMF switch was 86% +/- 6%. One patient died of infection and 3 of other causes. Serum creatinine concentration decreased from 248 +/- 15 micromol/liter before cyclosporine dosage reduction to 193 +/- 11 micromol/liter and 206 +/- 19 micromol/liter at 3 and 12 months after dosage reduction (both p < 0.01 versus baseline, n = 23). Of the 23 patients who remained on MMF at 12 months, a decrease in serum creatinine was documented in 19 (83%). Four patients showed no improvement or showed deterioration in renal function, and three of these progressed to end-stage renal failure. CONCLUSIONS: Chronic cyclosporine nephrotoxicity has a significant reversible component in most patients. A strategy of AZA/MMF switch combined with cyclosporine dosage reduction is generally well tolerated and results in short-term improvement in renal function in most patients. Close vigilance is required during the first 12 months after AZA/MMF switch because both acute rejection and infection may occur.

Azathioprine↗