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R Mathias

Publications and source records attributed to R Mathias.

At least 19 recordsLinked to original sources
PubMed2006

Susceptibility to ozone-induced airway inflammation is associated with decreased levels of surfactant protein D.

BACKGROUND: Ozone (O3), a common air pollutant, induces exacerbation of asthma and chronic obstructive pulmonary disease. Pulmonary surfactant protein (SP)-D modulates immune and inflammatory responses in the lung. We have shown previously that SP-D plays a protective role in a mouse model of allergic airway inflammation. Here we studied the role and regulation of SP-D in O3-induced inflammatory changes in the lung. METHODS: To evaluate the effects of O3 exposure in mouse strains with genetically different expression levels of SP-D we exposed Balb/c, C57BL/6 and SP-D knockout mice to O3 or air. BAL cellular and cytokine content and SP-D levels were evaluated and compared between the different strains. The kinetics of SP-D production and inflammatory parameters were studied at 0, 2, 6, 12, 24, 48, and 72 hrs after O3 exposure. The effect of IL-6, an O3-inducible cytokine, on the expression of SP-D was investigated in vitro using a primary alveolar type II cell culture. RESULTS: Ozone-exposed Balb/c mice demonstrated significantly enhanced acute inflammatory changes including recruitment of inflammatory cells and release of KC and IL-12p70 when compared with age- and sex-matched C57BL/6 mice. On the other hand, C57BL/6 mice had significantly higher levels of SP-D and released more IL-10 and IL-6. Increase in SP-D production coincided with the resolution of inflammatory changes. Mice deficient in SP-D had significantly higher numbers of inflammatory cells when compared to controls supporting the notion that SP-D has an anti-inflammatory function in our model of O3 exposure. IL-6, which was highly up-regulated in O3 exposed mice, was capable of inducing the expression of SP-D in vitro in a dose dependent manner. CONCLUSION: Our data suggest that IL-6 contributes to the up-regulation of SP-D after acute O3 exposure and elevation of SP-D in the lung is associated with the resolution of inflammation. Absence or low levels of SP-D predispose to enhanced inflammatory changes following acute oxidative stress.

Animals↗
PubMed2004

Genome scan for loci linked to mite sensitivity: the Collaborative Study on the Genetics of Asthma (CSGA).

Mite sensitivity has been reported to be a major risk factor for asthma. As part of the Collaborative Study on the Genetics of Asthma (CSGA), a genome scan using mite reactivity (Dermatophagoides Pteronyssinus (Der p) and Dermatophagoides farinae (Der f)) as the phenotype was conducted. In 287 CSGA families, 122 were informative for linkage. Evidence supporting linkage was observed for regions on chromosome 19 (D19S591, lod=2.43, P=0.0008; D19S1037, lod=1.57, P=0.007) and chromosome 20 (D20S473/D20S604, lod=1.41, P=0.01). All three ethnic groups appeared to contribute to the evidence for linkage on chromosome 20. African-American families gave strongest support for linkage on chromosomes 3 (D3S2409, lod=1.33, P=0.01), 12 (D12S373, lod=1.51, P=0.008) and 18 (ATA82B02, lod=1.32, P=0.01). Caucasian families showed strong evidence for linkage on chromosome 19 (D19S591, lod=3.51, P=0.00006). Hispanic families supported linkage on chromosomes 11 (D11S1984, lod=1.56, P=0.007), 13 (D13S787, lod=1.30, P=0.01) and 20 (D20S470, lod=1.71, P=0.005). These results suggest that multiple genes may be involved in controlling skin reactivity to Dermatophoigoies.

Animals↗
PubMed2001

Optical dysfunction of the crystalline lens in aquaporin-0-deficient mice.

Aquaporin-0 (AQP0), a water transport channel protein, is the major intrinsic protein (MIP) of lens fiber cell plasma membranes. Mice deficient in the gene for AQP0 (Aqp0, Mip) were generated from a library of gene trap embryo stem cells. Sequence analysis showed that the gene trap vector had inserted into the first exon of Aqp0, causing a null mutation as verified by RNA blotting and immunochemistry. At 3 wk of age (postnatal day 21), lenses from null mice (Aqp0(-/-)) contained polymorphic opacities, whereas lenses from heterozygous mice (Aqp0(+/-)) were transparent and did not develop frank opacities until approximately 24 wk of age. Osmotic water permeability values for Aqp0(+/-) and Aqp0(-/-) lenses were reduced to approximately 46% and approximately 20% of wild-type values, respectively, and the focusing power of Aqp0(+/-) lenses was significantly lower than that of wild type. These findings show that heterozygous loss of AQP0 is sufficient to trigger cataractogenesis in mice and suggest that this MIP is required for optimal focusing of the crystalline lens.

Age Factors↗
PubMed2001

Detection of immunoglobulin G in the lung and liver of hamsters with visceral leishmaniasis.

Several organs are affected in visceral leishmaniasis, not only those rich in mononuclear phagocytes. Hypergammaglobulinemia occurs during visceral leishmaniasis; anti-Leishmania antibodies are not primarily important for protection but might be involved in the pathogenesis of tissue lesions. The glomerulonephritis occurring in visceral leishmaniasis has been attributed to immune complex deposition but in other organs the mechanism has not been studied. In the current study we demonstrated the presence of IgG in the lung and liver of hamsters with visceral leishmaniasis. Hamsters were injected intraperitoneally with 2 x 10(7) amastigotes of Leishmania (Leishmania) chagasi and the presence of IgG in the liver and lung was evaluated at 7, 15, 30, 45, 80 and 102 days postinfection (PI) by immunohistochemistry. The parasite burden in the spleen and liver increased progressively during infection. We observed a deposit of IgG from day 7 PI that increased progressively until it reached highest intensity around 30 and 45 days PI, declining at later times. The IgG deposits outlined the sinusoids. In the lung a deposit of IgG was observed in the capillary walls that was moderate at day 7 PI, but the intensity increased remarkably at day 30 PI and declined at later times of infection. No significant C3 deposits were observed in the lung or in the liver. We conclude that IgG may participate in the pathogenesis of the inflammatory process of the lung and liver occurring in experimental visceral leishmaniasis and we discuss an alternative mechanism other than immune complex deposition.

Animals↗
PubMed2000

Proportion positive for Epstein-Barr virus, cytomegalovirus, human herpesvirus 6, Toxoplasma, and human immunodeficiency virus types 1 and 2 in heterophile-negative patients with an absolute lymphocytosis or an instrument-generated atypical lymphocyte flag.

OBJECTIVES: To determine the proportion of patients with evidence of an acute infection due to Epstein-Barr virus (EBV), cytomegalovirus (CMV), human herpesvirus 6 (HHV-6), Toxoplasma, or human immunodeficiency virus types 1 and 2 (HIV-1 and HIV-2) in heterophile-negative patients with an absolute lymphocytosis or an instrument-generated atypical lymphocyte flag, and to develop a cost-effective testing algorithm for managing such heterophile-negative patients. DESIGN: We conducted a prospective investigation of 70 selected outpatients who tested negative for heterophile antibody in association with an absolute lymphocytosis or instrument-generated atypical lymphocyte flag. The control population consisted of 50 patients who were heterophile negative and had a normal absolute lymphocyte count and no instrument-generated atypical lymphocyte flag. SETTING: A large outpatient laboratory system. INTERVENTION: Viral serology for HHV-6 was performed by immunofluorescence, and all other serologies were performed by enzyme-linked immunoassay. All testing was for immunoglobulin (Ig) M antibodies, except in the case of HIV. RESULTS: The proportion of study patients positive for EBV was 40% (28/70); for CMV, 39% (27/70); for HHV-6, 25% (16/65); for Toxoplasma, 3% (2/70); and for HIV, 0% (0/70). All 50 control patients were negative for EBV IgM antibodies. When patients with more than 1 positive viral test were excluded from analysis, positivity was 20% (9/45) for EBV, 22% (10/45) for CMV, 9% (4/45) for HHV-6, and 2% (1/45) for Toxoplasma. Utilizing hypothesis-generating logistic regression models, Downey type II atypical lymphocytes were significantly associated with EBV positivity (P =.006), while Downey type III lymphocytes were significantly associated with HHV-6 positivity (P =.016), and there was a trend for the association of Downey type I lymphocytes with CMV positivity (P =.097). CONCLUSIONS: A positive viral serology was identified in 70% of study patients. Multiple positive serologies complicate establishing a definitive diagnosis. Potential cost savings may be associated with the use of an appropriate testing algorithm.

Adolescent↗
PubMed1997

Randomised double-blind placebo-controlled study on adverse effects of rubella immunisation in seronegative women.

BACKGROUND: The objective of our study was to investigate the association of adverse clinical musculoskeletal and neurological events in healthy postpartum women with live attenuated (RA27/3 strain) rubella-virus vaccine, and to assess the frequency of acute and recurrent arthralgia and arthritis and associations with acute and recurrent muscle pain (myalgia) and neurological manifestations (paraesthesias). METHODS: We used a randomised placebo-controlled, double-blind design in a community setting. 636 women were enrolled and, after 90 women dropped out, 546 healthy women aged 18-41 years, who were rubella seronegative on routine screening were immunised parenterally with either monovalent live attenuated (RA27/3 strain) rubella vaccine (n = 270) or saline placebo (n = 276) in the postpartum period. Outcome measures were the occurrence of acute and persistent or recurrent joint manifestations (arthralgia or arthritis) at 1, 3, 6, 9, and 12 months after immunisation. Occurrence of muscle pain (myalgia), and neurological symptoms (paraesthesia) was also assessed at the same times. FINDINGS: 543 women completed 1-month follow-up. 456 women completed the 12-month assessment. There were no differences at the time of immunisation between rubella vaccine and placebo groups in distribution of age, ethnic origin, parity, time between delivery and immunisation, breastfeeding history, or histories of earlier rubella vaccination or joint complaints. Results indicated a significantly higher incidence (p = 0.006; odds ratio = 1.73 [95% CI = 1.17-2.57]) of acute joint manifestations in rubella-vaccine recipients (30%) than in placebo recipients (20%). Frequency of chronic (recurrent) arthralgia or arthritis was only marginally significant (p = 0.042; 1.58 [1.01-2.45]). INTERPRETATION: RA27/3 rubella vaccine given to seronegative women during the postpartum period was significantly associated with development of acute arthralgia or arthritis. Although the numbers of women assessed and length of follow-up revealed only marginally significant differences in persistent or recurrent joint manifestations between rubella vaccine and placebo recipients, it is possible that susceptible women who are given rubella vaccination may experience this outcome.

Adolescent↗
PubMed1997

Identifying the need for curriculum change. When a rural training program needs reform.

OBJECTIVE: To identify what changes should be made in the University of British Columbia's rural family practice training program curriculum to help graduates be better prepared to practice. DESIGN: Two cross-sectional surveys via mailed questionnaires: one designed to measure physicians' self-reported preparedness for practice and the other to measure the importance of various rural family medicine components. SETTING: Rural training program graduates and preceptors representing rural communities in British Columbia. PARTICIPANTS: Thirty-nine graduates of the rural training program between 1982 and 1991 and 14 community-based rural training program preceptors representing eight communities throughout the province participated in this study. MAIN OUTCOME MEASURES: Percentage of graduates of the rural program who reported themselves to be underprepared on each family practice item and preceptors' mean scores for the attributed importance to rural practice of each item on this questionnaire. RESULTS: A list of curriculum areas most in need of reform was created. This list included trauma, counseling skills, radiology, vacuum extraction, fracture care, exercising community leadership, cost-effective use of diagnostic tests, using community health resources, obtaining hospital privileges, ophthalmology, dermatology, otolaryngology, personal and professional growth, relationships with other physicians, and personnel issues. CONCLUSIONS: Using both the level of graduates' self-reported underpreparedness and the attributed importance of elements of rural practice, as indicated by the preceptor survey, we developed a list of the areas of the rural training program curriculum most in need of reform.

Adult↗
PubMed1996

Training for rural practice. Are graduates of a UBC program well prepared?

OBJECTIVE: To evaluate preparedness for rural practice and to ascertain where graduates of a community-based rural training program practise. DESIGN: Mailed cross-sectional survey. SETTING: Rural communities in British Columbia. PARTICIPANTS: Graduates of the University of British Columbia's (UBC) rural training program from 1982 to 1991 and a random sample of non-program-trained rural BC physicians. MAIN OUTCOME MEASURES: Self-reported preparedness for rural practice in various areas of family medicine and in aspects of professional and personal life in rural settings. Locations of practice. RESULTS: Rural program graduates reported themselves better prepared in family medicine, community medicine, practice management, and behavioural science. Non-program-trained rural physicians thought themselves better prepared in medical subspecialties. Responses in pediatrics, obstetrics and gynecology, and surgical preparation showed no important differences. Rural program residents were located in rural areas (51%), regional settings (20.5%), and metropolitan areas (17.9%). CONCLUSION: Graduates of the UBC rural training program consider themselves better prepared for rural family practice than non-program-trained rural physicians in several areas of family practice. Most graduates of the program were practising in rural and regional settings.

Adult↗
PubMed1993

Renal bone disease in pediatric and young adult patients on hemodialysis in a children's hospital.

Renal bone disease has been well defined in adult patients receiving chronic dialysis and in children on peritoneal dialysis/continuous ambulatory peritoneal dialysis. However, little is known about the histologic features in patients undergoing chronic hemodialysis in a children's hospital center. Twenty one patients, aged 17.5 +/- 1.5 yr, on hemodialysis for 35 +/- 6 months underwent iliac crest bone biopsies and deferoxamine infusion tests. Nineteen of 21 patients were receiving oral calcitriol. The 21 patients were classified by histomorphometry as follows: osteitis fibrosa, 5; mild hyperparathyroidism, 3; normal histology, 3; aplastic, 6; and mixed lesions, 4. Four of 21 patients were surface positive for aluminum, and seven other patients stained positive for iron in bone. Serum parathyroid hormone (PTH) levels correlated directly with the bone formation rate (r = 0.84) and with eroded bone perimeter (r = 0.67). Eight of the nine patients with serum PTH levels above 125 pg/mL had marrow fibrosis. All patients with serum calcium levels < 10.0 mg/dL and serum PTH levels > 125 pg/mL had either osteitis fibrosa or mixed bone lesions--a group of patients that might benefit from aggressive vitamin D therapy. In contrast, an examination of patients with serum calcium levels > 10.0 mg/dL and serum PTH levels < 65 pg/mL correctly identified three out of three patients with aluminum-related bone disease. These findings suggest that measurements of serum intact PTH levels by the immunoradiometric assay method may be valuable in distinguishing high-turnover lesions from normal or low-turnover skeletal lesions in this population.

Adolescent↗
PubMed1993

A case of a hepatitis B infected practitioner.

The first case of a dental practitioner infected by a blood-borne pathogen to be identified to the College of Dental Surgeons of B.C. and reviewed by the Dental Profession Advisory Program's infected practitioner program committee is reported. After the committee was contacted, the infected practitioner's status was evaluated and guidelines were provided to him. This paper reviews the committee's decision-making process, particularly with respect to its management of the infected dental practitioner.

British Columbia↗
PubMed1989

Quantitative risk approaches for formaldehyde.

Formaldehyde presents unique data that highlight significant issues in the extrapolation of animal studies to human risk assessments. Formaldehyde causes rare nasal cancer in rats at 15 ppm, but not at lower levels of 2 ppm and 0.5 ppm in the range of human exposures. Mice and hamster studies even at high levels have results similar to low dose rats. Higginson et al. reviewed the human epidemiology studies and concluded that no excess cancer risk was observed; and if a risk exists, it is very low. Formaldehyde is a natural metabolite--the human body turns over 51 g/day. Cells, therefore, have detoxification and other defence mechanisms to formaldehyde. Recent CIIT biomechanism results elucidate these factors. These data raise two issues: First, the appropriateness of linear quantitative risk methodology given the non-linear nature of the biological data. Either a non-linear (threshold) statistical model or NOEL approach are appropriate risk assessment techniques for formaldehyde. Second, the rare nasal cancer observed in rats also occurs in control animals. A comparison of relative risk between background and low formaldehyde exposures has been calculated for both groups. Non-linear (MLE) 5 stage multistage models estimate 0 per million risk from both background and 1 ppm of formaldehyde exposure. Linear or upperbound (95%) estimates are 7,200/million from background and 5,000/million from 1 ppm formaldehyde. These estimates have a significant impact on formaldehyde regulatory programs for warning labels and "safe" exposure levels.

Environmental Pollutants↗
PubMed1984

EEG sleep evaluation of depression in borderline patients.

In this study the sleep of borderline patients and patients with primary nondelusional depression showed sleep continuity disturbance and greater REM activity and density (particularly during the first REM period) than that of normal control subjects. First-night REM latencies were more variable in the borderline than in the depressed group, but by the second night both groups showed shorter REM latencies than the controls. The similarities in EEG sleep suggest a relationship between borderline disorder and the affective spectrum and cast doubt on the definition of the borderline disorder as a pure character type.

Adolescent↗
PubMed1983

Impaired renal and extrarenal potassium adaptation in old rats.

Young (3 to 4 months) and old (21 to 22 months) rats were fed either a regular or high potassium (K) diet. After acute potassium chloride infusion, the fraction of infused K excreted (K efficiency) was similar in rats on a normal diet (57 +/- 3%, young, vs. 61 +/- 2%, old). With high K feeding there was a significant increase in the young, 69 +/- 4%, but not in the old rats, 62 +/- 2%. Na-K ATPase activity was markedly reduced in the renal medulla of old rats on a regular or high K diet. In addition, the response to acute K loading was compared in acutely nephrectomized rats. In the young rats on a regular diet plasma K increased from 3.72 +/- 0.09 to 5.28 +/- 0.16 mEq/liter while with K ingestion the increase was significantly less, 3.62 +/- 0.07 to 4.75 +/- 0.12 mEq/liter. In the old rats plasma K increased similarly on a regular or high K diet, 3.68 +/- 0.10 to 5.68 +/- 0.33 mEq/liter and 3.76 +/- 0.06 to 5.97 +/- 0.30 mEq/liter, respectively. Thus, old rats have impaired renal and extrarenal adaptation, but they have a normal response to an acute K challenge. A reduction in Na-K ATPase may account for the defect in renal adaptation in the aged rats.

Adaptation, Physiological↗
PubMed1975

Prophylaxis of recurring urinary tract infection in females: a comparison of nitrofurantoin with trimethoprim-sulfamethoxazole.

Twenty-eight females with recurrent urinary tract infection were treated to eradicate their existing infections and then observed for recurrences while receiving one of the three following prophylactic regimens for 6 to 12 months: nitrofurantoin, 50 mg daily; one half tablet of trimethoprim-sulfamethoxazole (TMP-SMX) twice weekly; or one tablet of TMP-SMX once weekly. Preadolescent girls received half the adult doses. After completion of the course of prophylactic agent the patients were followed up at bimonthly intervals until infection recurred. After eradication of this new infection they were started on another prophylactic regimen. Six infections (1.0/patient-year) recurred in patients on nitrofurantoin, four infections (0.4/patients-year) reucrred in those receiving twice weekly TMP-SMX, and 12 infections (1.3/patient-year) in those receiving once weekly TMP-SMX. The mean interval between discontinuation of prophylaxis and recurrence of infection was 2.6 months. TMP-SMX in the doses used eliminated aerobic gram-negative rods from swabs from the anal canal in many patients. Gram-negative organisms resistant to trimethoprim did not cause infection either during or after therapy.

Administration, Oral↗