Biomedical subjects

D R Wilson

Publications and source records attributed to D R Wilson.

At least 37 records · Page 2Linked to original sources

PubMed2001

Grass pollen immunotherapy: symptomatic improvement correlates with reductions in eosinophils and IL-5 mRNA expression in the nasal mucosa during the pollen season.

BACKGROUND: Tissue eosinophilia and infiltration by T(H)2-type T cells are characteristic features of allergic rhinitis both after allergen challenge and during natural allergen exposure. Specific immunotherapy inhibits allergen-induced nasal eosinophilia. OBJECTIVES: We sought to assess, in the context of a randomized trial, the relationships between symptomatic improvement after immunotherapy and eosinophil numbers and IL-5 expression in the nasal mucosa during the pollen season. METHODS: Nasal biopsy specimens were taken from 37 adults with severe summer hay fever at baseline (out of season) and at peak season after 2 years of treatment with a depot grass pollen extract or placebo. Biopsy specimens were processed for immunohistochemistry by using mAbs against eosinophils (EG2), T cells (CD3), and IL-2 receptor-positive cells (CD25), as well as for in situ hybridization by using a sulfur 35-labeled antisense riboprobe directed against IL-5. RESULTS: Immunotherapy significantly reduced symptoms (49%, P =.01) and medication requirements (80%, P =.007) compared with placebo. There was a 400% increase (P =.004) in eosinophils during the pollen season in placebo-treated patients, which was inhibited in the immunotherapy group (20% increase, P =.04 between groups). Seasonal increases were also observed for CD25(+) cells (P =.002), CD3(+) cells (P =.02), and IL-5 mRNA-expressing cells (P =.03) in the placebo group but not in the immunotherapy group. A significant correlation was observed between eosinophils and IL-5 expression (r = 0.5, P <.05). Both eosinophils (r = 0.6, P <.02) and IL-5 (r = 0.6, P <.02) correlated with symptoms after immunotherapy. CONCLUSION: Improvement in symptoms after grass pollen immunotherapy may result, at least in part, from inhibition of IL-5-dependent tissue eosinophilia during the pollen season.

Biopsy↗

PubMed2001

Adenovirus-mediated wild-type p53 gene expression radiosensitizes non-small cell lung cancer cells but not normal lung fibroblasts.

PURPOSE: We compared the ability of adenoviral-mediated wild-type p53 RPR/INGN201(Ad5/CMV/p53) to radiosensitize non-small cell lung carcinoma (NSCLC) and normal lung fibroblast cells. MATERIALS AND METHODS: NSCLC cell lines (A549 and H322) and human lung fibroblast cells (MRC-9 and CCD-16) were used in this study. Radiosensitivity was determined by clonogenic assay and tumor growth delay. Expression of p53, Bax, and p21WAF1 protein were evaluated by immunoblot. A FITC conjugate of annexin V was used for flow cytometric detection of apoptosis. RESULTS: Clonogenic and apoptotic assays indicated that Ad5/CMV/p53 enhanced the radiosensitivity of both NSCLC cell lines. On the other hand, the two normal human fibroblast cell lines appeared to be resistant to the cytotoxic effects of Ad5/CMV/p53 and were not radiosensitized compared to the NSCLC cells. According to immunoblot analysis, Bax expression was increased in the NSCLC cells treated with the combination therapy; Bax expression, however, was unchanged in normal cells. In in vivo studies, tumor growth suppression was enhanced by this combination strategy in xenograft tumors growing in nude mice compared to Ad5/CMV/p53 or radiation therapy when used alone. CONCLUSIONS: Our data indicate that therapy using Ad5/CMV/p53 and irradiation in combination is more effective than either treatment when used alone on NSCLC cells, is not limited to cells with defective endogenous p53, and does not enhance the radiosensitivity of normal cells.

Adenoviridae↗

PubMed2001

Torsades de pointes associated with high dose levomethadyl acetate (ORLAAM).

A patient undergoing management of heroin dependency with high dosages of the long-acting methadone derivative, levomethadyl acetate HCl (LAAM; ORLAAM) developed a prolonged QTc interval and polymorphic QRS complexes on EKG consistent with torsades de pointes (TdP). The patient was taking other drugs known to prolong the QTc interval (fluoxetine and IV cocaine), and those known to antagonize the activity of the P450 enzymes responsible for the metabolism of LAAM and its active metabolite (fluoxetine, cocaine and marijuana). No previous reports have appeared in the literature attributing this adverse event to LAAM therapy; however, five similar cases have been reported to the manufacturer. Animal studies indicate that LAAM and metabolites prolong the action potential duration of myocardial cells. We propose that predisposed patients on high doses of LAAM may be at risk for developing TdP. Patients being treated with LAAM should receive dosages consistent with guidelines and be evaluated for concomitant diseases, interacting drug therapies, and EKG abnormalities.

Adult↗

PubMed2000

Gender vs sex.

Explore the source record for details and available documents.

Sex↗

PubMed2000

Adenovirus-mediated p16INK4a gene expression radiosensitizes non-small cell lung cancer cells in a p53-dependent manner.

We examined the influence of adenovirus-mediated wild-type p16INK4a (Ad/p16) expression on the radiation sensitivity of NSCLC cell lines, all of which lacked constitutive p16INK4a but each of which varied in p53 status: A549 (-p16INK4a/ +pRb/wt-p53), H322 (-p16INK4a/ +pRb/mt-p53), and H1299 (-p16INK4a/ +pRb/deleted-p53). The in vitro clonogenic survival results indicate that Ad/p16 enhanced the radiosensitivity of A549 but not H322 or H1299. Further analysis indicated that the apoptosis induced by combination therapy using Ad/p16 plus irradiation was dependent on the endogenous p53 status of the cancer cells. We performed Western blotting to analyse the p53 protein expression of A549 cells treated with either Ad/p16 or Ad/Luc. Endogenous p53 protein levels were higher in A549 cells transfected with Ad/p16 than in those transfected with Ad/Luc. Furthermore, when wt-p53 protein expression was restored in H1299 using Ad/ p53, Ad/p16 stabilized p53 protein expression and radiosensitized the cells. These results suggest that Ad/ p16-induced stabilization of p53 protein may play an important role in Ad/p16 mediated radiosensitization by enhancing or restoring apoptosis properties. Thus, Ad/ p16 plus radiation in combination may be a useful gene therapy strategy for tumors that have wt-p53 but nonfunctional p16INK4a.

Adenoviruses, Human↗

PubMed2000

Effect of augmentation on the mechanics of vertebral wedge fractures.

STUDY DESIGN: The effect of cement augmentation of wedge-fractured vertebral bodies on spine segment compliance was studied in 16 cadaver specimens. OBJECTIVES: 1) To assess the mechanical effects of cement augmentation of vertebral wedge fractures. 2) To determine whether a new reduction/injection procedure has the same mechanical effects as the established direct injection procedure. SUMMARY OF BACKGROUND DATA: Although wedge fractures cause pain and disability in hundreds of thousands of people, few effective treatments are available. Clinical studies have shown that cement augmentation, a new procedure, effectively relieves pain and restores mobility in patients suffering from weak or fractured vertebrae. However, only a few studies have examined the mechanics of vertebral augmentation. METHODS: A wedge fracture was created in the middle vertebra of 16 three-vertebra cadaver spine segments. Neutral and full-load compliance of each fractured spine segment in flexion/extension and lateral bending were assessed by measuring the relative rotation of the vertebral bodies in response to applied moments. Eight of the fractured vertebral bodies were then augmented using direct injection, while the remaining eight fractured vertebral bodies were augmented using a combined reduction/injection procedure. Compliance of the augmented segments was then assessed. RESULTS: Augmentation significantly reduced the neutral compliance (reduction of 25% +/- 23%) (mean +/- standard deviation) and the full-load compliance (reduction of 23% +/- 20%) in flexion/extension (P < 0.005). Augmentation also significantly reduced the neutral compliance (reduction of 34% +/- 20%) and the full-load compliance (reduction of 26% +/- 17%) in lateral bending (P < 0.0001). No significant difference was found between the two procedures for compliance reduction. CONCLUSIONS: Augmentation of wedge fractures using both direct injection and reduction/injection reduces spine segment compliance significantly.

Aged↗

PubMed2000

The components of passive knee movement are coupled to flexion angle.

Movement of the unloaded knee has been described in several studies by an "envelope of passive flexion", a description that does not describe or explain the widely reported coupling of internal tibial rotation to flexion. The objective of the current study was to show that the envelope of passive knee flexion can be reduced to a coupled path. Two hypotheses were tested: (1) in normal knees flexed passively, internal/external rotation, abduction/adduction and all three components of translation are coupled to flexion angle, and (2) the tibia rotates internally as the knee is flexed passively. Fifteen cadaver knees were flexed in a rig designed to apply minimal resistance to knee movement while three-dimensional kinematics of the femur relative to the tibia were measured with an electromagnetic tracking system. Each specimen displayed internal tibial rotation and posterior, proximal and medial displacement of a reference point with flexion, while a range of ab/adduction behaviour was observed. Mean absolute differences between the flexing and extending paths in normal specimens were under 2 and 0.2 degrees for internal/external tibial rotation and ab/adduction, respectively. Deviation from the movement path was resisted: when released after being displaced, the femur of each normal joint sprang back to its original position on the motion path. It was concluded that passive knee flexion can be described by a coupled path. Although the exact shape of the path is very sensitive to load and varies between knees, knee rotations and translations were always coupled to flexion, and internal tibial rotation with flexion was always observed.

Cadaver↗

PubMed2000

Biosafety of in vivo adenovirus-p53 intravesical administration in mice.

OBJECTIVES: To evaluate the biosafety and in vivo biodistribution of intravesical instillation of an adenovirus that contains human p53 gene. Mutations of p53, which are found in as many as 40% of transitional cell carcinomas, are associated with a poor prognosis and resistance to chemotherapy and radiation therapy. Restoration of wild-type p53 status by means of adenoviral-mediated therapy may enhance apoptosis and improve the response to therapy, but the issues of biosafety and toxicity have not yet been addressed. METHODS: Adenovirus-p53 (1 x 10(8), 1 x 10(9), and 5 x 10(9) pfu/mL) and luciferase reporter gene (5 x 10(9)) were instilled into the bladders of anesthetized female BALB/c mice. The mice were killed on days 1, 3, 6, and 13, and representative samples of the bladder, ureter, kidney, adrenal gland, ovary, liver, heart, and lung were removed for histologic evaluation. RESULTS: No histologic signs of toxicity were found. The hematologic and biochemical profiles of the mice were normal, with the exception of a transient elevation in liver function tests on day 1 in the three treatment groups. CONCLUSIONS: Intravesical instillation of adenovirus-p53 was well tolerated; the bladder urothelium appeared to prevent systemic dissemination. The results of these experiments support the safety of intravesical gene transfer by intravesical instillation.

Adenoviridae↗

PubMed2000

Effects of beach sand properties, temperature and rainfall on the degradation rates of oil in buried oil/beach sand mixtures.

Lysimeters located outdoors have been used to evaluate the decomposition of buried oily beach sand waste (OBS) prepared using Forties light crude oil and sand from different locations around the British coast. The OBS (5% oil by weight) was buried as a 12-cm layer over dune pasture sub-sand and overlain by 20 cm of dune pasture topsoil. Decomposition rates of oil residues averaged 2300 kg ha(-1) in the first year and the pattern of oil decomposition may be represented by a power curve. Oil decomposition was strongly related to the temperature in the OBS layer, but was also significantly affected by rainfall in the previous 12 h. The CO(2) flux at the surface of the treatment lysimeters followed the relationship [log(10) CO(2) (mg C m(-2) h(-1))=0.93+0.058x OBS temp. (degrees C)-0.042x12 h rain (mm)]. There was considerable variation in the rate of oil decomposition in sands collected from different sites. Sand from Askernish supported most microbial activity whilst sand from Tain was relatively inactive. The decomposition process appeared to cease when the sand became saturated with water, i.e. temporarily anaerobic. However, decomposition recommenced when the soil dried out. The fastest rate of decomposition occurred in sand from one of the two sites predicted to have high populations of hydrocarbon-degrading bacteria. Larger particle size and higher Ca content may also be significant factors governing the rate of decomposition.

Journal Article↗

PubMed2000

Educating future physicians for Ontario: phase II.

In 1990, a collaborative project was launched to determine what the people of Ontario expect of their physicians and how the programs that prepare future physicians should be changed in response. The project, called Educating Future Physicians for Ontario (EFPO), brought together the five Ontario medical schools, the Council of Ontario Faculties of Medicine (COFM); a nonprofit, charitable organization, Associated Medical Services (AMS); and the Ontario Ministry of Health. The first phase ran for five years and was described in the November 1998 issue of Academic Medicine. After an external review, the project was continued for a second phase (EFPO II) for four more years until December 1998; that second phase is the topic of this article. EFPO II (1) focused more on residents' education; (2) emphasized four of the EFPO I-created physician roles in project activities; (3) maintained the province-wide, inter-institutional medical education framework of phase I, but fostered greater involvement of the seven sites (five medical schools and two regional health centers) in project activities; (4) stressed five project components (e.g., needs assessment and community partnerships) and worked for collaboration among components at all sites; (5) enhanced the original EFPO I Fellowship Program by adding residents and community fellows to the existing fellowships and by initiating leadership development activities, all of which bode well for the future leadership of medical education in Ontario. Students and residents played a vital role in EPFO II. Most of EFPO II's objectives were met, but the overall view of external reviewers was that the project was less successful than EFPO I. For example, the impact on clinical education, especially residency education, was less than anticipated. On the other hand, the project helped encourage the wide adoption of the eight physician roles that originated in EFPO I and advanced faculty development and assessment activities based on these roles. A third phase of EFPO concerning continuing medical education was planned, but support was not available. However, one of the funders will continue to support the successful fellowship and leadership program and the provincial education network for the next three years. Overall, the two phases of EFPO substantially modified medical education in Ontario to make it more responsive to evolving social needs.

Education, Medical↗

PubMed1999

Radiosensitization of human tumor cell lines induced by the adenovirus-mediated expression of an anti-Ras single-chain antibody fragment.

The expression of activated ras genes has been implicated as a contributing factor to the radioresistance of tumor cells. As a strategy for compromising Ras protein activity and potentially enhancing the radiosensitivity of tumor cells, we have investigated the application of the AV1Y28 adenovirus, which expresses a single-chain antibody fragment directed against p21 Ras proteins. The ability of AV1Y28 transduction to modulate radioresponse was investigated using four human tumor cell lines--U251 glioblastoma, MIA PaCa-2 pancreatic carcinoma, and the colon carcinomas SW620 and HT29. Cultures were exposed to sufficient levels of AV1Y28 to transduce more than 90% of the cells; 24 h later, cultures were exposed to ionizing radiation, and clonogenic cell survival was determined. Tumor cell survival was reduced by 40-50% when the tumor cell lines were exposed to AV1Y28 only. In addition, for each tumor cell line, AV1Y28 exposure enhanced the level of radiation-induced cell killing. Dose enhancement factors at a surviving fraction of 0.1 ranged from 1.3 to 1.5. Furthermore, for each of the cell lines, the surviving fraction at 2 Gy was significantly reduced by AV1Y28 exposure. In contrast to the results seen in tumor cells, the radiosensitivity of a normal human fibroblast cell line was not affected by AV1Y28. These data indicate that this anti-Ras adenovirus enhances the radiosensitivity of tumor cells but does not affect the radiosensitivity of normal cells.

Adenoviridae↗

PubMed1999

Hamstrings cocontraction reduces internal rotation, anterior translation, and anterior cruciate ligament load in weight-bearing flexion.

Strengthening of the hamstrings is often recommended following injury and reconstruction of the anterior cruciate ligament. It has been suggested that hamstrings activity stabilizes the knee and reduces anterior cruciate ligament load during weight-bearing flexion; however, the effects of hamstrings cocontraction on the kinematics and mechanics of the normal knee have not been assessed at physiological load levels. The aim of this study was to determine whether the addition of hamstrings force affects knee rotations, translations, and joint and quadriceps force during flexion with loads at physiological levels applied to the muscles and joints. Eight cadaveric knee specimens were tested with a servohydraulic mechanism capable of applying controlled dynamic loads to simulate quadriceps and hamstrings muscle forces throughout a physiological range of motion. A constant vertical load of physiologic magnitude was applied to the hip, and quadriceps force was varied to maintain equilibrium throughout flexion. Two conditions were tested: no hamstrings force and a constant hamstrings force equivalent to the vertical load. Hamstrings force significantly reduced internal rotation (p<0.0001) and anterior translation (p<0.0001), increased quadriceps force (p<0.0001) and normal resultant force on the tibia (p<0.0001), and reversed the direction of the shear force on the tibia (p<0.0001). These results suggest that hamstrings strengthening following anterior cruciate ligament injury may benefit anterior cruciate ligament-deficient and reconstructed knees by reducing the load in the ligament; however, they also imply that this comes at the expense of efficiency and higher patellofemoral and joint forces.

Aged↗

PubMed1999

Asthma in the Army: 1985-1996.

Based on comparison between data obtained on medical discharges from the Army due to asthma for 1985 and for 1994-1995, this study shows that the current Army policy on asthma and recruiting is effective but could be improved. Plans aimed at improving the current screening programme are introduced.

Adolescent↗

PubMed1999

Socioeconomic risk factors and population-based regional allocation of healthcare funds.

Using the notion of professional uncertainty a population-based proxy need measure for hospital services was developed. Its relationship with socioeconomic variables and Standardized Mortality Ratios (SMR) was investigated in an attempt to develop an adjustment factor for socioeconomic risk factors beyond age-sex adjustment to be used for a population-based healthcare funding formula for Alberta. The data used are 1990, 1991, 1992 vital statistics and hospital separation abstracts, 1991 census data and Refined Diagnosis Related Group (RDRG) case weights. Geographic units studied were the 26 federal electoral districts in Alberta using postal codes as a linkage geo-code between census and hospital utilization and death data. SMRs, age-sex standardized per capita hospital utilization and proxy need rates were derived and correlated with socioeconomic variables derived from the census files. It appears that the poor, the less educated and aboriginals need more hospital services than the affluent, employed and educated, confirming previous findings. The unemployed tend to need more but use fewer services while immigrants and non-white ethnics tend to need and use fewer services. The unemployed, less educated and non-white ethnics are associated with positive correlation with premature mortality (SMR based on deaths under age 75 years), while the employed, highly educated tend to live longer. In general SMRs have positive but very low correlations with utilization and need rates suggesting that SMRs should not be used for resource allocation. Stepwise multiple regression analyses showed that the percentages of unemployed, immigrants, non-whites, aboriginals and those with education less than grade 9 explain about 90% of the variation in age-sex standardized hospital utilization rates. Percentages of unemployed, non-white ethnics, residents with education less than grade 9 and aboriginals explained 71% of variations in age-sex standardized per capita proxy hospital service need measures. Based on the results of regression analyses, a SEAM (Socio-Economic Adjustment Multiplier) scale was developed for utilization (SEAM-U) and proxy needs (SEAM-N). In essence a SEAM is a set of relative value (RV) multipliers applicable to a provincial common per age-sex adjusted capita allocation value to account for the impact of socioeconomic risk factors on hospital service needs or utilization. Finally, the resulting regression equations derived from the 26 Federal electoral district data were applied to Alberta's health regions, regional SEAMs were derived, and the impact of such adjustment was assessed.

Alberta↗

PubMed1999

Economic evaluation of risperidone in an outpatient population.

OBJECTIVE: To study the impact of risperidone use on the cost of services provided to severely mentally disabled outpatients and on hospital avoidance, and to analyze patterns in the use of concomitant medications as a surrogate marker of changes in adverse effects or patient well-being. METHODS: The patients were 31 clients of community mental health centers who had received risperidone for at least three months and for whom there were at least three months of available data on medication use and costs prior to risperidone treatment. The actual average monthly costs of community mental health services obtained from a county mental health board were compared with service costs prior to use of risperidone, using the patients as their own controls, and compared with a control group. RESULTS: Compared with the pre-risperidone period, the average cost per month of providing mental health services increased by 73.7% during the risperidone treatment period. Compared with the pre-risperidone period, the average total cost of treatment (including medications) increased by 113.3% during the risperidone treatment period. The average total cost of medication increased by 422.8% during the risperidone treatment period compared with the pre-risperidone treatment period. CONCLUSIONS: From the perspective of the community mental health board, risperidone treatment did not reduce the cost of services provided to these clients, but substantially and significantly increased total costs, including medication.

Ambulatory Care↗

PubMed1998

Alberta's Rural Physician Action Plan: an integrated approach to education, recruitment and retention.

This paper describes the development and characteristics of a comprehensive, integrated and sustained program for the education, recruitment and retention of physicians for rural practice in Alberta--the Rural Physician Action Plan. The participation of key stakeholders (including government, the provincial medical association, the licensing authority, faculties of medicine, practising rural physicians and regional health authorities) and a sustained program budget have been key organizational issues for success. Critical to the effectiveness of this program has been the focus on professional and lifestyle issues targeting 3 distinct groups: physicians in training, physicians in practice, and rural communities and health authorities. Substantial program funding since 1991-92 of up to $3 million per year has increased rural-based activities significantly. For example, 87% of medical students and 91% of residents in family medicine in Alberta now experience 4 weeks or more of rural practice. The authors believe that the historic issues and recent trends militating against recruitment and retention of rural physicians will continue unchecked without comprehensive and sustained approaches such as Alberta's Rural Physician Action Plan.

Alberta↗

PubMed1998

A repeatable alignment method and local coordinate description for knee joint testing and kinematic measurement.

A method for aligning cadaver knee specimens to a mechanical testing rig and determining local anatomical coordinate systems using landmarks identifiable on plane X-rays is introduced. Three sequential rotational alignments arc used to position the femur and tibia relative to the coordinate system of the testing mechanism. To validate this methodology five independent observers aligned the same knee specimen. The maximum error in the alignment orientations of the tibia and femur was 2.2 from the mean. These small misalignments produced variations of up to 4.7 in tibio-femoral rotations measured during knee flexion. Kinematic measurements of 15 specimens aligned using this procedure indicate that knee alignment is reproducible and physiologically relevant.

Biomechanical Phenomena↗

PubMed1998

Ligaments and articular contact guide passive knee flexion.

The aim of this study was to test the hypothesis that the coupled features of passive knee flexion are guided by articular contact and by the isometric fascicles of the ACL, PCL and MCL. A three-dimensional mathematical model of the knee was developed, in which the articular surfaces in the lateral and medial compartments and the isometric fascicles in the ACL, PCL and MCL were represented as five constraints in a one degree-of-freedom parallel spatial mechanism. Mechanism analysis techniques were used to predict the path of motion of the tibia relative to the femur. Using a set of anatomical parameters obtained from a cadaver specimen, the model predicts coupled internal rotation and ab/adduction with flexion. These predictions correspond well to measurements of the cadaver specimen's motion. The model also predicts posterior translation of contact on the tibia with flexion. Although this is a well-known feature of passive knee flexion, the model predicts more translation than has been reported from experiments in the literature. Modelling of uncertainty in the anatomical parameters demonstrated that the discrepancy between theoretical predictions and experimental measurement can be attributed to parameter sensitivity of the model. This study shows that the ligaments and articular surfaces work together to guide passive knee motion. A principal implication of the work is that both articular surface geometry and ligament geometry must be preserved or replicated by surgical reconstruction and replacement procedures to ensure normal knee kinematics and by extension, mechanics.

Anterior Cruciate Ligament↗