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Biomedical subjects

I Walker

Publications and source records attributed to I Walker.

At least 37 records · Page 2Linked to original sources
PubMed2000

Experimental infection of colostrum deprived piglets with porcine circovirus 2 (PCV2) and porcine reproductive and respiratory syndrome virus (PRRSV) potentiates PCV2 replication.

Experimental infection of colostrum-deprived (CD) pigs with a combined inoculum of porcine circovirus 2 (PCV2) and porcine reproductive and respiratory syndrome virus (PRRSV) potentiated the replication and distribution of PCV2 virus, when compared with pigs inoculated with PCV2 alone. The replication and distribution of PRRSV in dually infected pigs was not enhanced, when compared to pigs inoculated with PRRSV alone. The mechanisms involved in the potentiation of PCV2 replication in PCV2/PRRSV and PCV2/porcine parvovirus (PPV) dually infected pigs may relate to the fact that monocyte/macrophage cell types are common targets of these 3 viruses.

Animals↗
PubMed2000

Allogeneic or autologous bone marrow transplantation (BMT) for non-Hodgkin's lymphoma (NHL): results of a provincial strategy. Ontario BMT Network, Canada.

In 1986, the bone marrow transplant centers in Ontario agreed to a strategy for the treatment of patients with NHL. Suitable patients would undergo autotransplant but be referred for allotransplant if they had persistent marrow involvement or an inadequate marrow/stem cell harvest. Data of all patients were recorded in a database. We reviewed this database to compare these transplant modalities with respect to overall survival, rate of relapse and treatment-related mortality. Between January 1986 and August 1997, 429 patients underwent BMT for NHL - 385 autotransplants and 44 allotransplants. Sixty-eight percent of patients received their transplant for aggressive NHL, while the others had indolent lymphoma. Three-year actuarial survival did not differ between allogeneic and autologous BMT: 71% vs 62%, respectively (P = 0.5330 by log-rank testing). Three-year actuarial rate of relapse was lower after allotransplant than autotransplant: 6% vs 41%, respectively (P = 0.0006 by log-rank testing). Treatment-related mortality was higher after allotransplant than autotransplant: 23% vs 6%, respectively (P = 0.001 by chi2 analysis). For further comparison, autotransplant patients were randomly matched 2:1 with the allotransplant patients for age +/- 5 years, disease status at BMT, disease histology, and year of BMT. In the matched comparison, survival did not differ (relative risk of death after allotransplant: 0.711 (95% CI: 0.309-1.637)). Relapse rate was significantly lower in the allotransplant group (relative risk of relapse for allotransplant: 0.190 (95% CI: 0.043-0.834)) and treatment-related mortality was not significantly different (relative risk for allotransplant: 1.425 (95% CI: 0.527-3.851)). In conclusion, a review of a provincial strategy for treatment of NHL, shows that survival is not different after allogeneic or autologous BMT, but the rate of relapse is lower after allotransplant. These data support continuing the current provincial strategy.

Adolescent↗
PubMed2000

Stereology of PCB 128-induced ultrastructural alterations in the rat liver.

Hepatocyte cytoplasmic alterations were stereologically determined in male and female Sprague-Dawley rats fed PCB congener 128 (2,2',3,3',4,4'-hexachlorobiphenyl) in concentrations of 0.05, 0.5, 5, 50 ppm, or corn oil in diets daily for 13 weeks. A significant increase (p < 0.05) in the volume-fraction of smooth endoplasmic reticulum (SER) was measured in the female rats fed a diet containing 5 or 50 ppm of the congener and a significant increase was revealed in the male rats at doses of 0.5 and 50 ppm. Because drug metabolizing enzymes are bound to the SER, proliferated profiles may imply heightened enzyme activity necessary to metabolize the PCB. An elevation in volume-fraction of rough endoplasmic reticulum (RER) was measured in the hepatocytes of the male rats fed 5 ppm of the congener and none of the concentrations significantly enhanced the level of RER profiles in the females. The volume-fraction values of mitochondria, peroxisomes or lipid droplets of the hepatocytes in either the males or the females were not significantly different, as were the baseline volume-fraction of parameters studied between the male and the female rats. We determined for PCB 128, when administered in a diet to Sprague-Dawley rats, the no observable adverse effect level (NOAEL) is < 0.5 ppm.

Animals↗
PubMed1999

The clinical utility of CMV surveillance cultures and antigenemia following bone marrow transplantation.

At our institution, the cytomegalovirus (CMV) prophylaxis protocol for allogeneic bone marrow transplant (BMT) recipients who are CMV-seropositive or receive marrow from a CMV-seropositive donor consists of a surveillance bronchoscopy approximately 35 days posttransplant. Patients with a positive surveillance bronchoscopy for CMV receive pre-emptive ganciclovir. In order to determine the utility of other screening methods for CMV, we prospectively performed weekly CMV antigenemia, and blood, urine and throat cultures from time of engraftment to day 120 post-BMT in 126 consecutive patients. Pre-emptive ganciclovir was given to 11/81 patients (13.6%) because of a positive surveillance bronchoscopy for CMV. Results of CMV blood, urine and throat cultures and the antigenemia assay done prior to or at the time of the surveillance bronchoscopy were analyzed for their ability to predict the bronchoscopy result. The antigenemia test had the highest positive and negative predictive values (72% and 96%, respectively). The ability of these tests to predict CMV disease was evaluated in the 70 patients with a negative surveillance bronchoscopy who did not receive pre-emptive ganciclovir. Of 19 cases of active CMV disease, CMV antigenemia was positive in 15 patients (79%) a mean of 34 days preceding symptoms. Blood cultures were positive in 14/19 patients (74%) a mean of 31 days before onset of disease. CMV antigenemia is useful for predicting the surveillance bronchoscopy result, and also predicts the development of CMV disease in the majority of patients missed by the surveillance bronchoscopy.

Adolescent↗
PubMed1999

A randomized controlled trial comparing plasma removal with white cell reduction to prevent reactions to platelets.

BACKGROUND: Recent data suggest that most reactions to platelets are caused by white cell (WBC)-derived cytokines that accumulate in the plasma portion of the component during storage. On the basis of this theory, the effectiveness of two interventions to prevent reactions, poststorage WBC reduction and plasma depletion, were compared. STUDY DESIGN: A multiple crossover design was used, in which platelet components for transfusion to a patient randomly were WBC reduced after storage, or the plasma supernatant was removed. Adults >17 years of age, with a hematologic disease requiring platelet transfusion support, were eligible for the study. Patients were assessed for signs and symptoms characteristic of a reaction during, immediately after, and 1 hour after transfusion. Reactions were graded as mild, moderate, or severe. Interleukin 6 levels were also measured in the transfused platelet components. RESULTS: There were 380 analyzable platelet transfusions to 30 patients. The frequency of reactions was 25.8 percent (48/186) in the transfusions of poststorage WBC-reduced platelets and 17.0 percent (33/194) in the transfusions of plasma-depleted platelets (p<0.008). The severity of the reaction was graded by the patient. Severe reactions occurred more frequently in connection with poststorage WBC-reduced platelets than with plasma-depleted platelets: 33.4 percent (16/48) versus 18.2 percent (6/33), respectively (p = 0.048). Regression analysis identified interleukin 6 as the most significant of the evaluated factors in its correlation with the risk of reaction. CONCLUSION: Plasma removal is more effective than poststorage WBC reduction in preventing reactions, especially severe reactions to platelets.

Adolescent↗
PubMed1998

Surveillance for factor VIII inhibitor development in the Canadian Hemophilia A population following the widespread introduction of recombinant factor VIII replacement therapy.

In the Fall of 1994 the majority of Canadian Hemophilia A (Factor VIII (F.VII) deficiency) patients who were receiving replacement therapy were converted to Recombinant Factor VIII (rF.VIII) from plasma derived products. This decision was taken and funded by the Canadian Blood Agency following the advice of the Association of Hemophilia Centre Directors of Canada (AHCDC) who considered this to be the safest replacement therapy available. Although it was the considered opinion of the AHCDC that there was no evidence available to support the theoretical concern that rF.VIII may prove more immunogenic than plasma derived products, patient follow up included intensive surveillance of all patients converted for this complication. A central reference laboratory was established and plasma specimens obtained before and 6-12 months following conversion to rF.VIII were referred for evaluation for inhibitor development by the classical Bethesda Assay. By concensus of the referring centers a Bethesda Unit (BU)/activity of 0.5 or greater was considered to be clinically significant. No increase in the incidence of inhibitor development has been recorded in 478 patients followed for one year after conversion. This pattern has not changed in 339 of these patients followed for a further year. Of interest was the finding by the reference laboratory that 8.0% of patients had BU activity of 0.5 or greater before conversion to rF.VIII. Many of these individuals lost this activity after conversion to rF.VIII as did others who appeared to have developed inhibitory activity during the first year of follow up but became inhibitor free in the second year of therapy. Overall, the incidence of true inhibitor development, i.e. negative pre-/positive post-conversion to rF.VIII, in this population of Hemophilia A patients was 2-3% over 2 years. This is similar to the incidence in patients treated with plasma derived products. These data emphasize the need for rigorous baseline evaluation in such investigations and the heterogeneity of the inhibitor response as assessed by in vitro assay. It was concluded that, although no attempt was made to correlate these in vitro data with clinical observations including F.VIII recovery and survival, the use of rF.VIII in hemophiliacs previously treated with plasma derived products was not associated with an increase in F.VIII inhibitor development.

Canada↗
PubMed1998

Monitoring soluble interleukin-2 receptor levels in related and unrelated donor allogenic bone marrow transplantation.

Acute graft-versus-host disease (GVHD) is effected by donor T lymphocytes which have been stimulated by host antigens. Activated donor T lymphocytes express interleukin-2 receptor (IL-2R), which is comprised of three subunits (alpha, beta, gamma). During activation, the a IL-2R subunit (CD25) is shed from the receptor complex and can be measured in the circulation. Soluble IL-2Ralpha (sIL-2R) levels are increased in states of immune activation including GVHD, and could theoretically be used as a guide to therapy. Since IL-2Ralpha expression is an early marker of T cell activation, we investigated: (1) if an increase in sIL-2R is specific for acute GVHD; and (2) if serial sIL-2R levels can identify patients with early GVHD, prior to the onset of clinical tissue damage (effector function). Weekly sIL-2R levels were monitored in 36 patients undergoing matched related (n=23) or matched unrelated (n=13) allogeneic bone marrow transplantation (BMT). There was no significant difference in sIL-2R levels between matched related and matched unrelated recipients. Patients with acute GVHD (n=19, 53%) demonstrated higher sIL-2R levels, than those without during weeks 2 and 3 post-BMT (P=0.02 and 0.04, Mann-Whitney U test, two-tailed). In patients with acute GVHD, the rise in sIL-2R preceded the clinical signs of GVHD (16/19 patients). However, patients with sepsis demonstrated a trend towards higher sIL-2R levels at week 1 and significantly greater levels by week 4 (P=0.02). Furthermore, patients with veno-occlusive disease (VOD) (25%) also had significantly higher sIL-2R levels at week 2 (P=0.03). We conclude that although sIL-2R levels increase in patients with acute GVHD, similar increases are seen in patients with VOD and/or sepsis and therefore, as a single biochemical marker, we find that serial measurements of sIL-2R lacks sufficient specificity to guide GVHD therapy.

Acute Disease↗
PubMed1998

Puerperal thromboprophylaxis: comparison of the anti-Xa activity of enoxaparin and unfractionated heparin.

Low molecular weight heparins are used extensively for thromboprophylaxis. The aim of this study was to compare the activity of the low molecular weight heparin, enoxaparin, 20 mg and 40 mg, given once per day with unfractionated heparin, 7500iu given twice per day, in terms of their anti-Xa activity in puerperal women following caesarean section and with an additional risk factor for venous thromboembolism. Seventeen women were randomised to receive one of the three treatments. The anti-Xa activity associated with each treatment was measured prior to treatment and at 2, 4, 6, 12 and 24 hours. The mean anti-Xa values of the groups receiving enoxaparin, 20 mg and 40 mg, were significantly higher than those of the group receiving unfractionated heparin. There was no difference between the two enoxaparin groups in terms of the anti-Xa activity profiles. This study suggests that the use of enoxaparin is superior to unfractionated heparin in terms of anti-Xa activity.

Anticoagulants↗
PubMed1998

A detailed comparison of the performance of the standard versus the Nijmegen modification of the Bethesda assay in detecting factor VIII:C inhibitors in the haemophilia A population of Canada. Association of Hemophilia Centre Directors of Canada. Factor VIII/IX Subcommittee of Scientific and Standardization Committee of International Society on Thrombosis and Haemostasis.

The Bethesda assay is widely used to monitor the development and progress of Factor VIII:C inhibitors. Factor VIII stability in the substrate plasma (normal pool) is compromised by pH shift and reduction in protein concentration. Preliminary study, by Verbruggen and colleagues (8), suggested a reduction in spuriously positive assay results may result from buffering the normal pool plasma substrate with imidazole to pH 7.4 and substituting Factor VIII deficient plasma for imidazole buffer in the control incubation mix. These laboratory findings have now been confirmed by the performance of both the standard and the modified Bethesda assays in parallel on 877 patient samples screened during the Factor VIII:C Inhibitor Surveillance Program instituted following the conversion of all Canadian haemophilia A patients to recombinant Factor VIII. Although this study does not address the question of the clinical significance of spurious positive assays, these laboratory findings do support the conclusions of Verbruggen and the modified assay has recently been endorsed by the Factor VIII/IX Subcommittee of the SSC.

Antigen-Antibody Reactions↗
PubMed1997

Intramarrow cytokine gene transfer by adenoviral vectors in dogs.

Daily systemic administration of hematopoietic growth factors can be associated with dose-limiting systemic side effects. To overcome this, we have investigated hematopoietic cytokine gene transfer to the marrow cavity of dogs by direct intramarrow injection of adenoviral vectors. In marrow culture, replication-deficient (E1-deleted) adenoviral vectors were able to transduce marrow stromal cells, demonstrating 30-fold greater expression than from other marrow cell types. High-level (ng/ml) cytokine production from transduced stromal cells persisted for 14 days in culture. Because adenovectors could efficiently transduce marrow stromal cells in culture, we investigated if stromal cells could also be transduced in vivo following direct intramarrow vector injection. Adenovectors with genes for interleukin 6 (IL-6) and Lac Z (beta-galactosidase) were injected directly into the marrow cavity of dogs resulting in protein expression localized to within the treated marrow. To evaluate this approach further in dogs, we constructed a vector expressing biologically active canine granulocyte-macrophage colony stimulating factor (GM-CSF). 293 cells infected with ADGM-CSF demonstrated prevalent GM-CSF mRNA by Northern blot and 135 +/- 30 ng/ml of protein as measured by enzyme-linked immunosorbent assay (ELISA). In vitro bioactivity of protein expressed was confirmed by canine GM colony-forming assay (CFU-GM). In vivo high-level protein production was noted in supernatants of marrow aspirates 72 hr following direct intramarrow administration of ADGM-CSF (baseline mean +/- SEM, 27 +/- 22 ng/ml, 72-hr sample 921 +/- 461 ng/ml). A localized myeloid expansion of marrow and significant peripheral leukocytosis (neutrophilia) were noted in all ADGM-CSF-treated dogs. Peripheral blood changes lasted for up to 3 weeks in dogs following single intramarrow injection. Thus, adenoviral cytokine expression from the marrow of a single large bone (ilium) led to compartmentalized expression of growth factor and an increase of hematopoiesis sufficient to cause peripheral blood changes in a large animal model.

Adenoviridae↗
PubMed1997

A comparative study on the use of virus and antibody detection techniques for the diagnosis of La Piedad Michoacan paramyxovirus (LPMV) infection in pigs.

La Piedad Michoacan paramyxovirus (LPMV) is newly recognized paramyxovirus that has been associated with neurologic and reproductive disorders in pigs in Mexico. To date, no comparative study of methods for the diagnosis of infection with this virus has been published. In this study, we identified tissues containing maximum virus load to optimize virus isolation procedures, and we compared this method to a rapid diagnostic test employing immunostaining of impression smears for LPMV antigens. In addition, several of the available tests for detecting LPMV antibodies were compared for their sensitivity in detecting seroconversion. Pigs used for the study of virus load in tissues and serologic studies were inoculated at 17 days of age with 10(7.00) TCID50 of LPMV. Serial blood samples were collected from selected pigs, and selected pigs were necropsied over a 14-day period. Pigs used in the investigation comparing standard virus isolation techniques to immunostaining of impression smears were inoculated at 3 days of age as described above and necropsied over an 8-day period. The results demonstrate that in the 17-day-old pigs maximum virus titers were detected in olfactory bulb at 5 days postinoculation (PI) and in midbrain at 9 days PI. In addition, the most consistent recovery of high titer virus was from tonsil (3-9 days PI) and olfactory bulb (4-9 days PI). Immunostaining of impression smears was as sensitive as virus isolation when selected tissues (lung, midbrain, olfactory bulb) were compared, with virus detected by both methods in 11/13 samples and in 1 sample each by immunostaining and virus isolation, respectively. All of the serology tests investigated detected seroconversion in pigs by 8 days PI. The identification of target organs where highest virus titers are found combined with immunofluorescent methods for the detection of LPMV antigens and a comparative study of the available serologic tests should facilitate the selection of techniques suitable for any laboratory to diagnose LPMV infection in pigs.

Animals↗
PubMed1996

Social roles, social norms, and self-presentation in the quiz effect of Ross, Amabile, and Steinmetz.

The quiz effect describes the tendency of contestants, but not questioners, in a quiz-game setting to discount the arbitrary nature of their roles in over-attributing cleverness to the questioner. This tendency is generally viewed as an example of the fundamental attribution error and is usually explained in terms of cognitive processes. An alternative explanation is proposed that suggests that the effect reflects impression-management tactics, especially compliance to the norm of modesty. In the present Australian study, the quiz effect was replicated when questioners and answerers rated past behaviors. However, when future performance in a quiz-game setting was predicted, there was no evidence of the effect. These results are consistent with a normative, not cognitive, explanation of the effect.

Games, Experimental↗
PubMed1996

A sequential study of experimental porcine paramyxovirus (LPMV) infection of pigs: immunostaining of cryostat sections and virus isolation.

La Piedad Michoacan Paramyxovirus (LPMV) is a recently recognized paramyxovirus infecting pigs throughout Mexico. Disease syndromes observed in field cases associated with LPMV infection include neurologic, respiratory, and reproductive disorders. Clinical signs and the distribution of LPMV virus and antigen in tissue samples from pigs experimentally infected with LPMV by natural routes were studied. Severe neurologic disease and death occurred following experimental inoculation of 3- and 17-day-old pigs. All of the pigs inoculated at 3 days of age were either dead or moribund by 8 days after inoculation, whereas 30% of the pigs inoculated at 17 days of age were affected. Virus was consistently recovered from or demonstrated in tissues from the respiratory tract of both groups of pigs. LPMV and antigen were also demonstrated in central nervous system (CNS) tissues from these pigs; however, differences in virus distribution within the CNS were demonstrated in the 2 groups. In the pigs inoculated at 17 days of age, isolation of LPMV was restricted to the olfactory bulb and midbrain. In contrast, in the pigs inoculated at 3 days of age, isolation of LPMV was more widespread throughout the CNS tissue examined. Virus excretion studies indicated that nasal spread of LPMV was more important than fecal spread. Comparatively large quantities of infectious LPMV were consistently recovered from urine samples of experimentally infected pigs.

Animals↗
PubMed1996

Economic evaluation of allogeneic bone marrow transplantation: a rudimentary model to generate estimates for the timely formulation of clinical policy.

PURPOSE: To provide an evidence-based approach to the formulation of clinical policy with respect to allogeneic bone marrow transplantation (BMT) that involves perceived trade offs between two major factors: costs and consequences. The report also highlights key informational deficiencies. PATIENTS AND METHODS: Adults with acute myeloid leukemia (AML) in second complete remission (2CR) and those with acute lymphoblastic leukemia (ALL) in first complete remission (1CR) were assigned to BMT or control groups solely on the availability of a suitable donor. All hospital-borne costs were estimated, based on services used according to manual chart review, in four categories: diagnostic and therapeutic costs, professional fees, drug costs, and ward costs. Incremental costs and incremental life-years were calculated, and the quotient determined a cost per life-year gained by BMT for AML (2CR) and ALL (1CR). RESULTS: The incremental cost (in 1992 Canadian dollars) per life-year gained by BMT (cost-effectiveness) for AML (2CR) was $29,200; and for ALL (1CR) it was minus $29,200. CONCLUSION: For AML (2CR), allogeneic BMT creates better outcomes than standard treatment, but is more costly. For ALL (1CR), both the costs and outcomes are similar for BMT and standard therapy. Quality adjustments made to life-years gained did not change these conclusions.

Adolescent↗
PubMed1996

Delay in the diagnosis of glioblastoma multiforme: is age a factor?

Discrimination in the delivery of health care, based on the age of the patient, is attracting increased attention. We investigated this problem by studying possible age-related delay in diagnosis in patients treated for glioblastoma multiforme (GBM). A total of 213 charts of patients with GBM seen from 1972 to 1992 were evaluated for type and duration of symptom, with 204 charts having sufficient data to be analyzed. The mean and median duration of symptoms for the entire group was 48.9 and 28 days, respectively. No age-related difference in duration of symptoms was noted. In light of the increasing incidence of GBM in patients above 60 years of age, further investigation of other possible areas of age discrimination in patients with GBM is warranted.

Adult↗
PubMed1995

The Canadian Hemophilia Registry as the basis for a national system for monitoring the use of factor concentrates.

BACKGROUND: Canada's publicly funded blood system has recently introduced high-purity concentrates as the standard treatment for individuals with hemophilia. The added cost and the need to document patient outcomes have prompted the consideration of a national blood product monitoring system. STUDY DESIGN AND METHODS: This study investigates the suitability of the Canadian Hemophilia Registry (CHR) as the basis of such a monitoring system by assessing the degree to which it represents users of factor concentrates. RESULTS: Currently, there are 1978 individuals registered with the CHR, of whom 1594 (81%) have hemophilia A and 384 (19%) have hemophilia B. The total prevalence is 7.2 per 10(5) population, with the prevalence of severe cases being 2.3 per 10(5). This overall prevalence is similar to that seen in other countries with national registries. The CHR national prevalence also compares favorably with that in the province of Quebec, where registration of users of blood products is compulsory. The CHR figures indicate that the number of persons currently infected with human immunodeficiency virus, both alive and dead, is 652, which is similar to the number of applicants (658) to the federal government's assistance program. The registry is stable, and the number of persons with severe cases, other than young children, newly registered or lost to follow-up during the last 2 years is very small. CONCLUSION: The CHR includes the vast majority of factor concentrate users and is therefore ideal as the basis for a national monitoring system.

Adolescent↗
PubMed1995

Information access and donated gametes: how much do we know about who wants to know?

This paper reviews the methodological adequacy of the psychosocial literature on information access when donated gametes and embryos are used. In all, 10 major flaws were identified: (i) sample sizes were too small, (ii) sample selection procedures were ad hoc, (iii) there were no comparisons between current and past donors and recipients, (iv) there were no comparisons between current donors and recipients in the one study, (v) studies relied on just one partner from a recipient couple, (vi) donor motivation was assessed crudely, (vii) studies failed to clarify what was identifying and non-identifying information, (viii) links between researchers and clinics may have influenced respondents, (ix) response measurement was crude, and (x) data analysis was limited and basic. It is argued that these flaws prohibit any firm conclusions to be drawn either way about whether donors and recipients should disclose information, whether they should have access to information, or even whether donors and recipients want to have access to information about each other or to have information about themselves disclosed to the other party.

Attitude↗