PubMed Health⌕ Search

Biomedical subjects

R Burnett

Publications and source records attributed to R Burnett.

At least 19 recordsLinked to original sources
PubMed1997

Immunohistochemistry for light microscopy in safety evaluation of therapeutic agents: an overview.

The history of immunohistochemistry started in 1941 when Coons identified pneumococci using a direct fluorescent method. Then followed the indirect method, the addition of horseradish peroxidase, the peroxidase anti-peroxidase technique of 1979 and the use of the Avidin and Biotin complex in the early 1980s. This sequence of events can help one appreciate the differences in these various techniques and their increased sophistication and sensitivity. The technique has been applied in the field of safety evaluation of new pharmaceutical products. Examples of current projects are used to illustrate the scope of the application. The use of an antibody to detect proliferating cell nuclear antigen has, in a pilot study with the popliteal lymph node assay, provided a method of differentiating an irritant response to acetone from an immune response to hydrazine. In hydrazine-treated rats the proliferation is mainly in the follicular region whilst it is mainly sinusoidal in animals treated with acetone. In the guinea-pig maximisation test, initial work with dinitrochlorobenzene suggests that detection of Langerhans cells may aid the differentiation of an irritant from an immune response. The preclinical assessment of antibodies intended for therapeutic use in man requires immunohistochemistry to be used to identify any human tissues which show a cross-reactivity. The major problems are not in the test itself but in obtaining suitable material. Identification of hormones is a useful tool for assessing the effects of releasing factors and has proved useful in aiding tumour identification in routine carcinogenicity studies. In a rare case, detection of prolactin in cell deposits in the lungs of a rat confirmed that this was a metastasis from a pituitary carcinoma. The application of immunohistochemical techniques to preclinical assessment of drugs should always be considered. In particular, it is recommended that appropriate samples should be conserved from routine studies in order to permit these techniques to be performed, if considered appropriate in the light of findings during routine histological examination.

Animals↗
PubMed1996

Prediction of radiotherapy response of cervical carcinoma through measurement of proliferation rate.

Estimation of tumour proliferation may allow the design of individualised radiotherapy schedules to optimise response. This prospective study correlates the tumour proliferation rate of cervical carcinoma with response to conventional radiotherapy. The potential tumour cell doubling rate (Tpot) was estimated following flash labelling of the tumours in vivo using the DNA precursor, bromodeoxyuridine (BrdUrd); samples were analysed by flow cytometry. Tumour ploidy, DNA index and mitotic count were also assessed as was histological grade and type. Multiple biopsies from each tumour were obtained from 121 women. The median Tpot was 4.0 days, median S-phase duration 12.8 h and median adjusted labelling index 9.8%. Higher BrdUrd labelling was seen in patients who developed pelvic tumour recurrence following radiotherapy. This was the only biological/histological parameter with univariate and multivariate significance in relation to locoregional recurrence (P = 0.006 and P = 0.034 respectively). This study represents the first assessment of Tpot in relation to long-term response of cervical tumours treated by radiotherapy treatment. The association of high BrdUrd labelling and poor pelvic disease-free survival indicates the need for further research into the potential of radiotherapy schedule alteration to reflect tumour proliferation. The predictive value may be enhanced by combination with other biological parameters.

Aged↗
PubMed1995

DLA-identical bone marrow grafts after low-dose total body irradiation: effects of high-dose corticosteroids and cyclosporine on engraftment.

Previous studies found that marrow allografts from DLA-identical littermates resulted in survival of 60% of recipient dogs after an otherwise lethal dose of 450 cGy of total body irradiation (TBI), either because of successful allografts or autologous recovery after rejection of the allografts. Forty percent of dogs died with marrow aplasia after allograft rejection. The current study asked whether allogeneic engraftment could be enhanced and survival improved by treating allograft recipients with high doses of corticosteroids or with cyclosporine (CSP), administered either before or after transplantation. Five dogs in group 1 received corticosteroids beginning on day -5 and ending on day 32 after transplant. The starting dose was 12.5 mg of prednisone per kilogram orally twice daily. All five dogs rejected their allografts; three died early with marrow aplasia and two showed endogenous marrow recovery. Nine dogs received CSP from day -6 to day -1 before transplantation at a dose of 20 mg/kg/d intravenously administered in divided doses. All nine dogs rejected the marrow allograft; six died with marrow aplasia and three survived with endogenous marrow recovery. Seven dogs received CSP after transplantation at a dose of 30 mg/kg/d orally from day -1 to day 35. All seven had sustained allografts (two mixed chimeras and five complete donor-type chimeras) and became healthy long-term survivors without graft-versus-host disease. These results extend previous observations and confirm that grafts of marrow from DLA-identical littermates improved survival of dogs exposed to low but otherwise lethal doses of TBI. Additional therapy with high-dose corticosteroids administered peritransplantation and posttransplantation or CSP administered before transplantation neither enhanced the rate of allogeneic engraftment nor improved survival; however, CSP administered after transplantation resulted in successful allografts and event-free survival in all cases.

Adrenal Cortex Hormones↗
PubMed1995

The human MLL gene: nucleotide sequence, homology to the Drosophila trx zinc-finger domain, and alternative splicing.

We have previously reported the cloning of several cDNAs corresponding to the MLL gene. The predicted primary amino acid sequence of two of these clones, 14p-18B and 14-7, reveals nearly complete identity with parts of the sequences of HRX, ALL-1, and Htrx-1, including a Zinc-finger region with homology to the Drosophila trithorax gene. However, we found that there is a stretch of 39 amino acids that is absent from 14p-18B when compared to ALL-1 and HRX. Another sequence of three amino acids is present in ALL-1, but is absent from 14p-18B and HRX. Nucleotide sequence examination reveals that these differences arise from alternative splicing, suggesting that MLL, HRX, and ALL-1 each represents a different alternative splicing product from the same gene. At least two cDNA clones, 14-7 and 14p-18C, correspond to incompletely processed transcripts including intron sequences. Northern blots using a subclone of 14p-18B revealed mRNA species of 14-16 kb in size in various human tissues. RNase protection assays show that the splice variant containing exon 8 and lacking a 9-bp extension 3' of exon 12 is predominantly expressed in hematopoietic cell lines.

Alternative Splicing↗
PubMed1995

Depression in male and female patients undergoing cardiac surgery.

The present longitudinal study was designed to determine the prevalence of depression in male and female patients undergoing cardiac surgery, and to examine what factors are associated with depression before and after surgery. One day prior to surgery (T1), and one day prior to discharge from the hospital (T2), 141 patients completed a psychometric test battery including the Center for Epidemiological Studies Depression Scale (CES-D), the State-Trait Anxiety Inventory (STAI), and the Perceived Social Support Scale (PSSS). Data were also collected on 13 physiological measures. Forty-seven per cent of patients were depressed (defined as a score of 16 or above on the CES-D) at T1. Scores on the CES-D significantly increased from T1 (M = 15) to T2 (M = 20), with 61 per cent of patients classified as depressed at T2. Factors associated with depression at T1 were female gender, higher state anxiety, and less social support. Depressed patients at T2 were characterized by higher scores on the STAI at T2 and higher scores on the CES-D at T1. The prevalence of depression in cardiac surgery patients, particularly women, may be underrecognized and warrants increased attention.

Adult↗
PubMed1995

Transcardiac echocardiography during invasive intramedullary procedures.

We performed transoesophageal echocardiography in 111 operations (110 patients) which included medullary reaming for fresh fractures of the femur and tibia, pathological lesions of the femur, and hemiarthroplasty of the hip. Embolic events of varying intensity were seen in 97 procedures and measured pulmonary responses correlated with the severity of embolic phenomena. Twenty-four out of the 25 severe embolic responses occurred while reaming pathological lesions or during cemented hemiarthroplasty of the hip and, overall, pathological lesions produced the most severe responses. Paradoxical embolisation occurred in four patients, all with pathological lesions of the femur (21%); two died. In 12 patients large coagulative masses became trapped in the heart. Extensive pulmonary thromboembolism with reamed bone and immature clot was found at post-mortem in two patients; there was severe systemic embolisation of fat and marrow in one who had a patent foramen ovale and widespread mild systemic fat embolisation in the other without associated foraminal defect. Sequential analysis of blood from the right atrium in five patients showed considerable activation of clotting cascades during reaming.

Aged↗
PubMed1994

DLA-identical bone marrow grafts after low-dose total body irradiation: the effect of canine recombinant hematopoietic growth factors.

Previous studies found that bone marrow (BM) allografts from DLA-identical littermates resulted in survival of two thirds of recipient dogs after otherwise lethal doses of 450 to 600 cGy of total body irradiation (TBI) because of successful allografts or autologous recovery after rejection of the allografts. The current study asked whether survival could be further improved by treating allograft recipients with recombinant canine granulocyte colony-stimulating factor (G-CSF), stem cell factor (SCF), or G-CSF/SCF. Of 21 dogs, 14 (67%) receiving allografts but no growth factors survived, 10 with successful allografts (including 5 mixed chimeras) and 4 with autologous recovery; whereas 7 animals died, 5 from infections during BM aplasia and 2 from acute graft-versus-host disease. By comparison, 30 of 34 dogs (88%) receiving hematopoietic growth factors in addition to the BM graft survived, 17 with successful allografts (including 10 mixed chimeras) and 13 with autologous recovery; whereas 4 died, all with infection related to BM aplasia after rejection of the allograft. Survival was similar for recipients of G-CSF, SCF, or the combination of G-CSF and SCF. Logistic regression analyses, which accounted for possible effects of TBI dose, showed a trend for improved survival in dogs receiving growth factors (P = .09), no change in allogeneic engraftment (P = .74), and a slight increase in autologous recovery (P = .22). In agreement with previous data, we found that grafts of BM from DLA-identical littermates improved survival of recipient dogs exposed to low but otherwise lethal doses of TBI. A further improvement in survival could be achieved by additional treatment with G-CSF, SCF, or G-CSF/SCF. Results suggest that treatment by hematopoietic growth factors along with BM grafts should be considered for victims of radiation accidents.

Animals↗
PubMed1994

Use of (CA)n polymorphisms to determine the origin of blood cells after allogeneic canine marrow grafting.

We have used a polymerase chain reaction-based assay measuring polymorphic (CA)n repeats, a class of simple sequence repeats, to assess the success of allogeneic canine marrow transplants. Results were compared with those obtained with karyotype analysis of dividing cells in recipients that were sex mismatched with their marrow donors. Twenty recipients were conditioned for transplantation of genotypically DLA-identical littermate marrow by 450 cGy of total-body irradiation. In 2 recipients, results could not be compared, since either only cytogenetic or dinucleotide (CA)n marker data existed. Both dogs had autologous marrow recovery. In 15 of the remaining 18 recipients, complete agreement was found between the results obtained with dinucleotide (CA)n markers, cytogenetic studies, and granulocyte changes after transplantation. Seven of the 15 showed eventual autologous recovery, 6 displayed mixtures of host and donor cells, and 2 showed donor-type hematopoiesis. Two of the 18 dogs showed mixed chimerism with (CA)n markers and autologous recovery by cytogenetics, findings that may be related to differences in cells analyzed by the two techniques--i.e., all nucleated cells by (CA)n markers versus dividing cells by cytogenetics. In one additional recipient, results of marrow cytogenetics, granulocyte changes, and (CA)n markers were consistent with a successful allograft, while peripheral blood cytogenetics suggested autologous recovery, possibly the result of erroneous blood sampling. Polymerase chain reaction-based testing for dinucleotide repeat (CA)n polymorphisms, originally developed for genetic mapping in the dog, is useful and reliable when compared with cytogenetic studies, in assessing the success of allogeneic marrow transplants in dogs.

Animals↗
PubMed1994

Pharmacokinetics of inhaled pyrene in rats.

Male Wistar rats were exposed to micronized aerosol concentrations of a 14C-labeled model polycyclic aromatic hydrocarbon (pyrene) at 200, 500, and 800 mg/m3 for a period of 95 min. Both the 14C label and free pyrene were monitored in the blood, urine, and feces. At the termination of the blood sampling, three of the six rats per dose group were killed and the distribution of [14C]pyrene to eight major tissues was analyzed. The analysis of blood concentration data using a one-compartment pharmacokinetic model revealed that the uptake and elimination kinetic parameters were dose dependent, for both total radioactivity (pyrene plus metabolites) and for pyrene per se, over the range of exposures used in this study. The ratio of the percent excreted via the urinary and fecal routes, collected over a 5-d period postexposure was about 1.0 at each exposure level.

Absorption↗
PubMed1994

Prevalence of childhood asthma across Canada.

BACKGROUND: A large cross-sectional study provided an opportunity to estimate the prevalence of childhood asthma in several regions across Canada. METHODS: In 1988, approximately 18,000 questionnaires were distributed to the families of 5-8 year old children in 30 communities from the following six regions across Canada: the interior of British Columbia, southeastern Saskatchewan, southwestern Ontario, the central region of Ontario, southern Quebec, and the Maritimes (Nova Scotia and Prince Edward Island). These communities were free of point-source air pollutants and selected to represent a range of ambient sulphate concentrations. In all 14,948 questionnaires were returned representing an 83% response rate. RESULTS: Currently present, physician-diagnosed asthma was reported for 4.7% of children by their parents. Persistent wheezing was reported for 13% and persistent cough for 5.9%. Asthma was most common in the two Maritime provinces (7.4%), and least common in British Columbia (3.3%) and Quebec (3.4%). Similar regional differences were seen for persistent cough, persistent wheeze, and also hospital separation rates for asthma which were approximately 800 per 100,000 for the Maritimes and 396 per 100,000 for British Columbia. Differences persisted despite adjustments for several host and environmental (indoor and outdoor) characteristics. CONCLUSIONS: The east coast of Canada may be an endemic area of asthma in Canada. If confirmed by objective measures of asthma, a detailed aetiologic investigation could enhance understanding of this phenomenon and the major environmental determinants of asthma morbidity in general.

Age Factors↗
PubMed1994

Echocardiography of transatrial embolism during cemented and uncemented hemiarthroplasty of the hip.

We performed transoesophageal echocardiography on 20 patients with femoral neck fractures randomly treated with an uncemented Austin-Moore or cemented Hastings hemiarthroplasty. Cemented arthroplasty caused greater and more prolonged embolic cascades than did uncemented arthroplasty. Some emboli were more than 3 cm in length. In some patients the cascades were associated with pulmonary hypertension, diminished oxygen tension and saturation, and the presence of fat and marrow in aspirates from the right atrium.

Arthroplasty↗
PubMed1993

Relevance of history of injury to the diagnosis of meniscal tears.

A consecutive series of 217 arthroscopic meniscectomies has been reviewed in order to investigate the incidence of significant meniscal lesions without obvious precipitating injury. There were 10 bucket handle tears out of 117 (9%) with a mean age of 32 years with no significant injury; 18 flap tears out of 69 (26%) with a mean age of 40 years; and 7 out of 19 (37%) radial tears with a mean age of 36 years also had no significant injury. This study indicates that the absence of a history of injury in the young patient with a symptomatic knee does not exclude significant meniscal tears, such as a bucket handle, and therefore has implications for history taking and diagnosis.

Adolescent↗
PubMed1992

Modification of tumor promotion in the mouse skin by exposure to an alternating magnetic field.

Some epidemiological studies have suggested that exposure to an alternating magnetic field may increase the incidence of some cancers. Our earlier study of carcinogenesis in mouse skin, indicated that exposure to a magnetic field (MF) alone did not promote the growth of tumors. In the present experiment, the ability of a MF to act as a tumor copromoter was investigated. The dorsal skins of female SENCAR mice (6-7-weeks-old) were treated with 10 nmol of 7,12-dimethylbenzanthracene (DMBA) to initiate the carcinogenic process and then tumor development was promoted, for 23 weeks, by weekly applications of 4.9 nmol (0.3 microgram) of 12-0-tetradecanoylphorbal-13-acetate (TPA). One group of 48 mice were exposed to a 60-Hz magnetic field of 2 mT (20 Gauss) for 6 h/day 5 days/week, while a similar group (48 mice) were sham exposed. After week 12, the percentage of mice with tumors and the mean number of tumors per mouse, were higher for the group exposed to MF. At week 18, for example, where the differences between field and sham groups were statistically significant, the percentage of mice with tumors were, respectively, 25% and 8% (P less than 0.05, Fisher exact) and, the mean yield of tumors 1.9 +/- 0.69 and 0.65 +/- 0.46 (mean +/- S.E.M.) (P less than 0.05, Wilcoxon). At week 23 these differences were no longer statistically significant.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1992

Behavioral and cognitive-behavioral approaches to chronic pain: recent advances and future directions.

Behavioral and cognitive-behavioral approaches to chronic pain are receiving increasing attention from researchers and clinicians. This article reviews and highlights recent research advances and future research directions. Assessment research reviewed includes studies examining the social context of pain, the relationship of chronic pain to depression, cognitive variables affecting pain, and comprehensive assessment measures. Treatment outcome studies reviewed are those evaluating the effects of behavioral and cognitive-behavioral treatments for chronic pain. These studies focus on comparisons of behavioral treatment with control conditions, comparisons of two behavioral treatments, and prevention of chronic pain. Future directions for assessment and treatment research are outlined.

Chronic Disease↗
PubMed1991

Respiratory health effects of home dampness and molds among Canadian children.

In 1988, the authors conducted a questionnaire-based study on the health effects of the indoor environment in 30 Canadian communities. This paper focuses on the association between the respiratory health of young children and home dampness and molds. A total of 17,962 parents or guardians of schoolchildren received a questionnaire, and 14,948 (83.2%) questionnaires were returned. Children living in mobile homes, tents, and boats were excluded as were those with cystic fibrosis, leaving 13,495 children included in the study group. The housing stock was distributed as follows: 81% were one-family detached homes, 6% were one-family attached homes, and 13% were buildings for two or more families. Molds were reported in 32.4%, flooding in 24.1%, and moisture in 14.1% of the homes. Prevalences of all respiratory symptoms were consistently higher in homes with reported molds or dampness; i.e., adjusted odds ratios ranged from 1.32 (95% confidence interval 1.06-1.39) for bronchitis to 1.89 (95% confidence interval 1.58-2.26) for cough. The prevalence of home dampness or molds, 37.8%, indicates that it is an important public health issue. Further studies are required to elucidate the pathogenesis.

Canada↗