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Biomedical subjects

D Pollock

Publications and source records attributed to D Pollock.

At least 19 recordsLinked to original sources

Mapping quantitative trait loci associated with resistance to coccidiosis and growth.

To map QTL associated with disease resistance to avian coccidiosis and growth, two commercial broiler lines with different degrees of resistance to the disease were crossed to generate an F1 generation that was intercrossed to produce 314 F2 generation offspring. The F2 offspring were inoculated with sporulated oocysts of Eimeria maxima. Five disease-associated phenotypes were measured after the infection. Intertrait comparisons revealed that oocyst shedding was a good parameter for evaluating disease resistance or susceptibility. One hundred nineteen microsatellite markers, covering 80% of the chicken genome with an average marker interval of 25 cM, were used for genotyping of F1 parents and F2 offspring. Statistical analysis based on the data of four families revealed a locus on chromosome 1 associated with oocyst shedding (logarithm of odds = 3.46). The genetic mechanism of this locus appeared additive. The genomic scan also identified three potential growth QTL on chromosomes 1, 6, and 8. These results provide the foundation for further investigation to validate the QTL.

Animals↗

Screening for highly heterozygous chickens in outbred commercial broiler lines to increase detection power for mapping quantitative trait loci.

Two commercial broiler lines were used in an experiment to map quantitative trait loci (QTL) affecting disease resistance. Chickens from these lines were genotyped with 27 microsatellite markers to estimate heterozygosity and polymorphism information content (PIC), the probability that one parent is heterozygous at a marker locus and the other has a different genotype. Heterozygosity estimated from allelic frequencies was 0.52 for the two lines; however, heterozygosity calculated from actual counts of heterozygous loci was much lower (0.36) than the estimated heterozygosity. The PIC was 0.45 in these lines, and average allele number per marker locus was about 3.5. Twenty-five males produced from a cross between these two lines were screened with the DNA markers to select birds with high heterozygosity at marker loci. Mating simulation showed that uninformative matings could be reduced by about 5% if 12 pairs of males and females with the highest heterozygosity at marker loci were selected, which was about a 25% reduction in total uninformative matings. This experiment demonstrated that the heterozygosity and PIC in commercial broiler lines were low and selection for the birds with high heterozygosity at marker loci could increase informative content in chickens used in the experiments of QTL mapping, thus increasing detection power for QTL mapping.

Animal Husbandry↗

A clinically practical method of manually assessing polyethylene liner thickness.

BACKGROUND: Most orthopaedists do not have access to contemporary computer-assisted radiographic techniques and therefore must use manual radiographic methods to assess polyethylene wear. The accuracy of most manual methods, however, has not been verified on clinical radiographs. In this study, we used manufacturer-developed wear templates to measure polyethylene wear and compared that technique with two other commonly used manual radiographic methods. Our purpose was to compare the accuracy of these techniques and thus determine their usefulness in assessing polyethylene wear in individual patients. METHODS: We analyzed seventeen polyethylene liners that were retrieved during revision operations after a mean of 12.0 years in situ. With use of digital calipers, we directly measured the true minimum polyethylene thickness of the explanted liner. We then measured the polyethylene thickness on anteroposterior pelvic radiographs that had been made before the revision. Three different manual techniques were used to evaluate the radiographs: the Dorr method, the Livermore method, and the newly described wear-template method. The minimum polyethylene thickness that was calculated with use of each of these methods was compared with the thickness as determined by direct measurement of the explanted liner. RESULTS: The mean error for the Dorr method (1.54 +/- 1.21 mm) was significantly greater than that for both the Livermore method (0.07 +/- 0.62 mm) and the wear-template method (-0.04 +/- 0.28 mm) (p < 0.01). The mean error for the Dorr method was significantly greater than zero (p < 0.01), indicating that this method consistently overestimated the true measurement. In contrast, the mean errors for the Livermore and wear-template methods were not significantly different from zero (p = 0.64 and 0.58, respectively), indicating that these methods did not consistently underestimate or overestimate the true measurement. However, the large standard deviations for all three methods suggest that the ranges in error are wide. The limits of agreement for the Livermore technique ranged from a 1.17-mm underestimation to a 1.31-mm overestimation of the true thickness of the polyethylene; those of the wear-template technique were smaller, ranging from a 0.60-mm underestimation to a 0.52-mm overestimation. CONCLUSION: The practicing orthopaedist needs an accurate and efficient method for determining the polyethylene thickness of modular acetabular components. We found that the template method best met this requirement because it involved a simple procedure: placing the template over the radiograph and measuring the distance between the femoral head and the inner surface of the metal shell. The other methods were less accurate, required additional information from the manufacturer, were more time-consuming, and were not as easy to demonstrate to the patient.

Acetabulum↗

An estimate of the cost of conducting phase II trials in lung cancer.

OBJECTIVE: Although it is commonly assumed that clinical trials are more costly than standard therapy, there have been no previous studies of the cost of conducting phase II trials in lung cancer. We retrospectively analyzed two National Cancer Institute of Canada phase II trials in previously untreated small cell lung cancer (SCLC) to determine the costs of conducting the trials in a cancer treatment centre. Both studies were clinical trials undertaken as part of the NCIC's Investigational New Drug program: IND 69 and IND 50 evaluated docetaxel (taxotere) and gemcitabine, respectively. METHODS: data management costs in a Canadian cancer treatment centre were determined from the time estimates provided by data managers to complete various protocol related tasks. Nursing and pharmacy personnel measured the time and supplies necessary to prepare and administer the chemotherapy. Physician fees were determined from the type and number of care visits required by the clinical protocols. Laboratory tests and imaging studies were costed according to the Ontario Health Insurance Plan (OHIP) Schedule of Fees and Benefits. To estimate whether phase II trials are more costly than standard treatment, we determined the cost of four cycles of VP-16-cisplatin, a standard treatment for SCLC. RESULTS: The total cost of performing the docetaxel study was $18443 for an average cost per case of $1317 and an average cost per treatment cycle of $683. The gemcitabine study cost more, due to the fact that the drug proved to be active against SCLC and more cycles of therapy were administered to a larger number of patients. Laboratory and administration costs were also higher, because of the drug administration schedule. The total cost of this study was estimated to be $64670 and the average cost per patient entered was $2230 with an average cost per treatment cycle of $898. In comparison, the estimated cost of four cycles of VP-16-cisplatin chemotherapy was $3948 or $987 per treatment cycle. The major cost drivers in the clinical trials were laboratory and imaging tests which made up 17 and 39%, respectively, of the costs of the taxotere study, and 29 and 27%, respectively, for the gemcitabine study. Data management costs contributed 21 and 13% of the total costs, respectively. CONCLUSION: As the main cost drivers in these phase II clinical trials are laboratory and imaging tests, the cost of clinical trials could potentially be reduced by ensuring that only essential tests are required by protocol. Not surprisingly, the cost of conducting a trial of an active agent is greater than for an inactive agent, because more patients are treated and each patient receives more treatment. The implications for the per-case funding of phase II clinical trials are discussed.

Antineoplastic Combined Chemotherapy Protocols↗

Analysis of disease resistance-associated parameters in broiler chickens challenged with Eimeria maxima.

To determine an optimal dose for coccidial inoculation and to evaluate genetic resistance or susceptibility in individual chickens, broilers were inoculated with four different doses of Eimeria maxima oocysts. Body weight gain, fecal oocyst shedding, concentrations of plasma NO2- + NO3-, carotenoid, and interferon-gamma were measured at two different time periods postinfection. The results showed significant dose and sex effects on most parameters and interaction between dose and sex in some parameters. The dose effects were generally linear; however, some significant quadratic effects were also observed. The measurements from chickens inoculated with 10(4) oocysts displayed the highest correlation coefficients among oocyst shedding, body weight gain, and concentrations of carotenoid and NO2- + NO3-. An infection index, calculated from the correlated parameters, displayed high correlation coefficients with the parameters. The infection index may be a better parameter for evaluating individual genetic resistance against coccidial infection.

Animals↗

Antitransferrin receptor antibody-RNase fusion protein expressed in the mammary gland of transgenic mice.

Antibodies fused to human enzymes offer an alternative to specifically targeting tumors with antibodies linked to plant or bacterial toxins. Since large amounts of these reagents can be administered without eliciting non-specific toxicities, efficient methods of production are needed. The goal of this work was to express a complex immunoenzyme fusion protein (immunotoxin) in the mammary gland of transgenic mice. A chimeric mouse/human antibody directed against the human transferrin receptor (E6) was fused at its CH2 domain to the gene for a human angiogenic ribonuclease, angiogenin (Ang). It was expressed in the mammary gland of mice and secreted into mouse milk. Expression levels in milk were approximately 0.8 g/l. The chimeric protein retained antibody binding activity and protein synthesis inhibitory activity equivalent to that of free Ang. It was specifically cytotoxic to human tumor cells in vitro.

Animals↗

Use of a monoclonal antibody against an Escherichia coli O26 surface protein for detection of enteropathogenic and enterohemorrhagic strains.

A monoclonal antibody (MAb) was obtained from a mouse immunized with solubilized outer membrane proteins extracted from a bovine enterohemorrhagic strain of Escherichia coli (EHEC), O26. The MAb produced a strong immunoblot reaction at approximately 21 kDa for an O26 strain containing the intimin gene (eae) and verocytotoxin (VT), but not with an O26 eae- and VT-negative strain, or O157 eae- and VT-positive strains. The MAb was used in a sandwich enzyme-linked immunosorbent assay (ELISA) format to screen strains from animal and human sources, and all reactive strains were characterized for the presence of eae and the gene encoding VT factors by PCR. The antigen was detected in a group of strains containing a high proportion of O26, the majority of which were eae positive with or without VT; these were isolated mostly from animal enteritis cases but included a small number of human enteric isolates. Nonreactors included eae-positive (with or without VT) O157 strains and one O26 strain. In a survey of mixed cultures from both animal and human enteric disease, ELISA-positive reactions were obtained from 7.1 to 11.2% of samples from bovine, porcine, ovine, and human sources. The two human O8 and ten animal O26 ELISA-reactive pure strains obtained from these samples contained six eae- and/or VT-positive strains; the other six strains lost their ELISA positivity following storage at -70 degrees C, after which none were found to contain either eae or VT factors. The association of the antigen detected by the MAb with significant enteropathogenic E. coli and EHEC virulence factors in isolates from both animal and human enteric infections indicates a diagnostic potential for the assay developed.

Animals↗

Feline bone marrow transplantation: its use in FIV-infected cats.

The use of autologous and allogenic bone marrow transplantations (BMT) in FIV-infected and uninfected cats is a novel therapy for feline hematopoietic diseases and retroviral infections. A total of 13 specific pathogen-free (SPF) cats received either autologous or allogenic BMT and seven of these cats were also infected with FIV before autologous or allogenic BMT. All BMT recipients received total body irradiation of 900 cGy just before BMT. Two FIV-infected and four uninfected cats received autologous uninfected BM cells cryopreserved before BMT. Five infected and two uninfected cats received BM cells from allogenic uninfected donors (RBC-, MHC-, and cross-matched). MHC-matching was based on mixed leucocyte reaction (MLR) and the donor-recipient combination which was compatible by MLR analysis, was used in this study. Recipients were monitored for hematology, immunology, virology, and clinical signs. All FIV-infected and uninfected recipients of autologous BMT had complete engraftment with minimal complications. Uninfected recipients of allogenic BMT had a more severe clinical episode with slower rate of engraftment. None of these BMT groups had mortality. In contrast, only two of the five infected recipients of allogenic BMT survived for a significant period of time (23 and 50 weeks) and rest of the cats succumbed to transfusion reactions. Both infected BMT groups had persistent CD4/CD8 inversion, low CD4+ cell counts, and FIV infection of engrafted peripheral blood mononuclear cells (PBMC). Overall, successful autologous and allogenic BMTs were performed in FIV-free cats. All infected recipients of autologous BMT had compete engraftment and are currently alive, with thelongest survival time being over 1 year. Thus, BMT in combination with antiviral drug therapies may be an alternative therapy against retroviral infection.

Animals↗

Efficacy evaluation of prime-boost protocol: canarypoxvirus-based feline immunodeficiency virus (FIV) vaccine and inactivated FIV-infected cell vaccine against heterologous FIV challenge in cats.

OBJECTIVE: To evaluate the immunogenicity and prophylactic efficacy of immunization schemes employing a recombinant canarypoxvirus ('ALVAC')-based feline immunodeficiency virus (FIV) vaccine alone or in combination with an inactivated FIV-infected cell vaccine against homologous and heterologous FIV challenges in cats. METHODS: Specific pathogen-free cats were given a total of three immunizations with subtype A vaccines and challenged 4 weeks after the final immunization with 50 median animal infectious doses (ID50) of FIV-Petaluma, a subtype A isolate. Following the initial challenge, protected cats received a second challenge with 75 ID50 of FIV-Bangston, a subtype B isolate. FIV-specific humoral and cell-mediated responses were measured to determine the immune correlates of protection. RESULTS: Two of three cats immunized with the ALVAC FIV recombinants alone were protected from homologous FIV challenge in the presence of FIV-specific cytotoxic T-lymphocyte (CTL) responses but in the absence of FIV-specific humoral responses. All three cats immunized with the ALVAC-FIV recombinant and boosted with FIV-infected cell vaccine were also protected from homologous FIV challenge in the presence of both FIV-specific CTL and humoral responses. Partial to full protection was observed in ALVAC-FIV/FIV-infected cell vaccine-immunized cats against a heterologous FIV challenge given 8 months after the initial challenge. Two out of three cats had transient infection and the remaining cat had no sign of FIV infection at a dose at which all three control cats were readily infected. CONCLUSIONS: Immunization schemes employing ALVAC-based FIV vaccines in combination with inactivated FIV-infected cell vaccine generate protective immune responses that can cross-react with FIV isolates that are genetically distinct from the vaccine strains.

Animals↗

Patterns of dysphoria in a Puerto Rican urban community.

This study was undertaken to explore the prevalence of perceived dysphoria in a poor, urban, predominantly Puerto Rican community. A cross-sectional sample of 704 adult respondents were asked a single validated question, with a five-item Likert scale response, about their level of perceived dysphoria. Chi-squared analysis and Spearman's correlation coefficients were used to assess the association of level of dysphoria with social characteristics, barriers to health care, health status, and substance use. Linear regression modeling was used to control for confounding variables. Twenty percent of the respondents were dysphoric. Respondents with no health insurance or no source of health care were least likely to be dysphoric. Persons who perceived distance to the hospital and the doctor, and understanding language of the doctor and office staff as barriers to care were more likely to be dysphoric. Ethnicity was not correlated with level of perceived dysphoria; however, age, gender, and health status were found to be associated with level of dysphoria after controlling for other correlated variables. These results indicate that the psychological needs of communities need to be understood and interventions that are appropriate for the population need to be devised.

Adult↗

Development of FIV-specific cytolytic T-lymphocyte responses in cats upon immunisation with FIV vaccines.

Vaccine protection has been achieved in cats against experimental infection with feline immunodeficiency virus (FIV). Such protection has been attributed to FIV-specific humoral immunity, as well as cellular immunity of unknown mechanism(s). Since cell-mediated immunity plays a crucial role in the clearance of viral infections, this study evaluated the role of FIV-specific CTL in vaccine prophylaxis. Cats were immunised with inactivated FIV vaccines, reported to have > 90% vaccine efficacy. Significant levels of specific CTL activity were detected following the third immunisation. CTL activity persisted for several months and could be enhanced through a booster immunisation. The levels of CTL activity were comparable to those induced by a recombinant canarypoxvirus based FIV vaccine. These results suggest a possible role for CTL-mediated immunity in vaccine protection against FIV infection in cats.

Animals↗

Geropsychiatric consultation for African-American and Caucasian patients.

We assessed differences in the referral rates of African-American and Caucasian elderly for geropsychiatric consultation. Reasons for referral, assigned diagnoses, and interventions made were also compared. A retrospective chart review of psychiatric consultations was completed for patients aged 65 years and older for a 2-year period. Significantly more consultations were requested Caucasian elderly (6.2%) than for African-American elderly (3.8%). African-American elderly were referred for evaluation of psychosis significantly more often and for assessment of suicide potential significantly less often than Caucasians. Consultants diagnosed African-American elderly with psychotic disorders, specifically schizophrenia, and dementia significantly more often than Caucasians. Caucasian elderly were significantly more often diagnosed with mood disorders, especially depressive disorders. Interventions/recommendations made for Caucasian and African-American elderly did not differ for the most part. Recommendations for legal measures were suggested for African-American elderly more often than for Caucasians. Differences between Caucasian and African-American elderly were observed in consultation referral rates, reasons for referral, and psychiatric diagnoses made. The potential impact of cultural variables and the racial and age differences between hospital staff and patients may account for some of these findings. Further awareness of the needs of African-American elderly is required.

Black or African American↗

Expression of a bovine kappa-CN cDNA in the mammary gland of transgenic mice utilizing a genomic milk protein gene as an expression cassette.

Transgenic mice were produced by microinjection of a DNA construct composed of the bovine kappa-casein (kappa-CN) cDNA under the control of the goat beta-CN 5' promoter elements and 3' flanking regions into pronuclear-stage embryos. The gene construct targeted the expression of bovine kappa-CN RNA to the mammary gland and secretion of bovine kappa-CN in the milk. In the three lines studied (BC-7, BC-31 and BC-67) the transgene was stably integrated and propagated as a Mendelian locus. Expression of the bovine protein in lactating mice from the three transgenic lines was demonstrated by northern and western blots. In ten different tissues analysed by northern blotting, expression was confined to the mammary gland of lactating transgenic mice from line BC-7, with low-level expression also observed in the salivary gland of lines BC-31 and BC-67. Transgene expression in the mammary gland paralleled normal casein gene expression during lactation and was not observed in virgin females. The level of bovine kappa-CN mRNA expression on day 10 of lactation in hemizygous transgenic females in relation to endogenous mRNA of whey acid protein (WAP) gene expression was 14%, 69%, and 127% in lines BC-7, BC-31 and BC-67, respectively. No association between transgene copy number and expression was observed. The bovine kappa-CN concentration in milk on day 10 of lactation ranged from 0.94 to 3.85 mg of protein per ml of milk. The bovine kappa-CN expressed in mouse milk had the same molecular mass and immunoactivity with polyclonal antibodies as did kappa-CN from bovine milk. A high degree of variation in the production of bovine kappa-CN within each of the transgenic lines was observed.

Amino Acid Sequence↗

Forty years on: a war to recognise and win. How the tobacco industry has survived the revelations on smoking and health.

Nothing has significantly checked the growth of the tobacco industry since the introduction of smoking to Europe, and the industry has easily survived the 40 years since the first authoritative revelations about the health effects of smoking. Some explanations are offered and the tactics of the industry and the response of the UK Government are reviewed. The policies of British-American Tobacco and its subsidiaries, especially Brown and Williamson in the USA, are considered in detail, including the rejection of an early proposal for a pragmatic but honest deal. In particular, an internal document from 1970 is examined in which BAT purports to set policy for the whole industry. The document is revealed as showing far-sighted but cynical calculation, for instance, in limiting concessions to those countries where public and government awareness requires them. Examples of BAT activities are quoted to illustrate key points.

Advertising↗

Personhood and illness among the Kulina.

This article offers both a contribution to the ethnography of ethnomedicine among the Kulina Indians of western Amazonia--a region in which there has been little ethnomedical research--and an extended illustration of the value of the concept of "personhood" in the analysis of ethnomedical beliefs and practices. I argue that the current medical anthropological fixation on the Body is neither good ethnography nor productive theory, and I use the Kulina example to illustrate how the cultural dimensions of personhood provide a more satisfactory framework for the understanding of illness. Kulina conceptions of illness are closely linked to the substances and processes through which personhood is acquired, expressed, and transformed. I consider the two major categories of illness in Kulina ethnomedicine, and focus special attention on the more serious of these: potentially fatal illnesses that are linked to witchcraft and to the violations of prohibitions. I suggest how these illnesses serve as languages for the simultaneous negotiation of social issues and personhood.

Adult↗

Uniform prehospital data elements and definitions: a report from the uniform prehospital emergency medical services data conference.

One of the district and universal aspects of emergency medical service (EMS) is the belief that before its implementation many people were dying or being killed by ill-equipped, poorly trained "hearse drivers" and that this tragic state of affairs has been rectified by the advances in the prehospital phase of care. Except for cases of nontraumatic, out-of-hospital cardiac arrest there is almost no convincing scientific evidence to prove that prehospital care has had an impact on morbidity or mortality. At the very foundation of this problem is the lack of a set of broad-based, well-conceived, accurate, reliable, uniform EMS data. Many attempts have been made to develop a uniform EMS data set, but without a national consensus these have not achieved wide distribution. In 1992, with the assistance of the National Highway Traffic Safety Administration, the national consensus process began with a series of meetings involving many EMS agencies and organizations. This culminated in August 1994 with the development of an 81-item uniform EMS data set. We detail the prior attempts at data set development and outline the process leading to the this uniform, national EMS data set.

Data Collection↗