Search PubMed⌕ Search

Biomedical subjects

R Heywood

Publications and source records attributed to R Heywood.

At least 19 recordsLinked to original sources
PubMed2005

Development of an improved analytical method for the determination of carcinogenic polycyclic aromatic hydrocarbons in transformer oil.

Polynuclear aromatic hydrocarbons (PAHs) are natural constituents of transformer oils and are essential in prolonging transformer in-service lifetime. Issues concerning PAH carcinogenicity demand methods that provide qualitative and quantitative information on the PAH composition of new and in-service oils to allow informed operational decisions to be made. However, current analytical methods focus on PAH fingerprinting, as opposed to quantitative analysis and are also cumbersome, relying on the use of large (>100 ml) volumes of organic solvents, some of which are hazardous. This paper reports a method for the improved quantification of carcinogenic PAHs in transformer oils that is both simple and repeatable. The method uses commercially available solid-phase extraction columns and millilitre volumes of relatively non-hazardous solvents. Extraction efficiencies of > or =74% were obtained for the Environmental Protection Agency priority PAHs. The method has potential for automation and high-throughput analysis and thus is of interest to industries that use transformer oils.

Carcinogens↗
PubMed2005

An unusual case of segmental clavicle fracture.

Fracture of the clavicle is a common traumatic injury and comprises 4% of all fractures in adults. Amongst these, midshaft injuries account for the majority and medial fractures are uncommon. Whilst segmental fractures have been reported in the literature, concurrent lateral and medial injuries are very rare. These injuries are, therefore, susceptible to being missed, due to failure to look for a second injury after the initial diagnosis, and difficult X-ray interpretation around the area of the medial clavicle. The nature of segmental fractures can pose a difficult management problem for numerous reasons, and initial operative fixation is usually indicated. Early diagnosis is therefore imperative, and as such, clinical examination is essential even if an obvious mid or lateral shaft fracture is seen on X-ray. This unusual case of combined lateral and medial fractures was initially missed and the presentation and management is discussed.

Clavicle↗
PubMed2001

Quantification of polynuclear aromatic hydrocarbons in transformer oils by enzyme immunoassay.

Many polynuclear aromatic hydrocarbons (PAHs) are either known or suspected carcinogens and are a common constituent of mineral oils. Due to the large number of possible PAH structures, standard quantification methods fail since they either lack specificity or are too complex, requiring individual fractionation, identification, and quantification. A rapid, low-cost, novel analytical screening method, incorporating a silica-based solid-phase extraction (SPE) method linked to co-solvent dilution and quantification of total and carcinogenic PAH levels by immunoassay, is reported here. The method yielded high extraction efficiencies and minimal matrix effects. This novel approach yielded total and carcinogenic PAH levels x 5.7 and x 126, respectively, lower than that recorded by the industry-recognised BS2000 Pt. 346 (IP346) method which estimates the polyaromatic carbon (PAC) content of oils by gravimetry. The method is expected to be of benefit where an indication of PAH levels in oils is important for purchasing, management or disposal purposes and also for risk assessment and for appropriate labelling of oils in line with current legislation.

Carcinogenicity Tests↗
PubMed2000

Prospects for reducing and refining the use of dogs in the regulatory toxicity testing of pharmaceuticals.

A workshop was held to critically discuss the need for a nonrodent species and the role of the dog in regulatory toxicity testing of pharmaceuticals; to discuss opportunities to reduce and refine the use of dogs in preclinical toxicology; and to identify a number of specific recommendations which could be feasibly achieved to move the process forward. To facilitate a preliminary evaluation of the contribution of dog studies to the risk assessment process, anonymised, unpublished data were provided from fully evaluated, repeat-dose toxicity studies in the rat and dog. Results of the International Life Sciences Institute (ILSI) Human Toxicity Project were also presented and discussed. Analysis of the data demonstrated that the dog can provide additional toxicity information, which, in some cases, was shown to be predictive for humans. Discussions indicated that there is potential for achieving a reduction in dog use and several possible approaches were identified. To further the progress of this initiative, there is a need to collate the results of pharmacology, toxicology, and clinical studies to address some of the proposed approaches. One of the outcomes of the workshop will be the establishment of a steering group to co-ordinate data collation for further analysis.

Animal Testing Alternatives↗
PubMed1998

Induction of chromosome aberrations in peripheral blood lymphocytes after short time inhalation of nitric oxide.

INTRODUCTION: inhalation of nitric oxide (INO) leads to vasodilation of pulmonary vasculature in ventilated regions of the lung. The clinical use of INO, although not formally approved as a drug, is widespread. NO may rapidly form nitrogen dioxide (NO2) in an oxygen containing gas mixture. NO2 has been shown to induce chromosome aberrations and mutations in both animal and bacterial test systems. We investigated whether a 2-h exposure to NO would increase frequencies of cells with chromosome aberrations in peripheral blood lymphocytes of human volunteers. METHODS: 10 volunteers were exposed to inhaled NO 40 parts per million (ppm) for 2 h. Pre- and post-exposure blood samples were analysed. RESULTS: no statistically significant differences (p</=0.05) in chromosome aberrations were observed between pre- and post-exposure samples. CONCLUSION: no detectable increase of chromosome aberrations in human peripheral blood lymphocytes after 2 h of NO-inhalation 40 ppm was found.

Administration, Inhalation↗
PubMed1998

CD34+AC133+ cells isolated from cord blood are highly enriched in long-term culture-initiating cells, NOD/SCID-repopulating cells and dendritic cell progenitors.

The AC133 antigen is a novel antigen selectively expressed on a subset of CD34+ cells in human fetal liver, bone marrow, and blood as demonstrated by flow cytometric analyses. In this study, we have further assessed the expression of AC133 on CD34+ cells in hemopoietic samples and found that there was a highly significant difference between normal bone marrow and cord blood versus aphereses (p <0.0001) but not between bone marrow and cord blood. Most of the clonogenic cells (67%) were contained in the CD34+AC133+ fraction. Compared with cultures of the CD34+AC133- cells, generation of progenitor cells in long-term culture on bone marrow stroma was consistently 10- to 100-fold higher in cultures initiated with CD34+AC133+ cells and was maintained for the 8-10 weeks of culture. Only the CD34+AC133+ cells were capable of repopulating NOD/SCID mice. Human cells were detectable as early as day 20, with increased levels (67%) apparent 40 days post-transplantation. Five thousand CD34+AC133+ cells engrafted about 20% of the mice, while no engraftment was observed in animals transplanted with up to 1.2 x 10(5) CD34+AC133- cells. The CD34+AC133+ population was also enriched (seven-fold) in dendritic cell precursors, and the dendritic cells generated were functionally active in a mixed lymphocyte reaction assay. AC133+ cells should be useful in the study of cellular and molecular mechanisms regulating primitive hemopoietic cells.

AC133 Antigen↗
PubMed1995

Toxicological requirements for sclerosing agents or other chemicals for female sterilization.

There are no guidelines regulating the technologies available for Fallopian tube occlusion. Generally accepted regulatory requirements cannot be applied directly to the safety assessment of these technologies. The more appropriate guidelines are those regulating medical devices. Each method has to be evaluated on its own merits taking into consideration the duration of contact with tissue and the chemical and physical composition of the occlusive agents.

Drug Evaluation, Preclinical↗
PubMed1992

Carcinogenicity assessment of lonidamine by dietary administration to Sprague-Dawley rats.

Following chronic dietary administration of 20, 60 and 180 mg/kg per day of lonidamine for 2 years to groups of Sprague-Dawley rats, treatment-related non-tumour findings seen microscopically included the following: atrophy of the testis with associated changes in epididymis and pituitary at all dosages; neuropathy in the sciatic nerve accompanied by skeletal muscle atrophy which was dose-related, particularly in male animals. Neither the incidence of tumour-bearing animals, nor the spectrum of tumours seen, was significantly changed. In the females given 180 mg/kg per day an overall reduction in tumour incidence was noted, which was reflected in a significant reduction (P < 0.001) in mammary tumours.

Administration, Oral↗
PubMed1992

Age-related changes in thyroid structure and function in Sprague-Dawley rats.

Investigation of thyroid glands from 500 male and 500 female Sprague-Dawley rats, at time points of 8, 17, 30, 56, and 108 weeks of toxicity studies conducted at the Huntingdon Research Centre between 1981 and 1984, revealed age-related structural and functional changes that have previously not been well documented. The number of ultimobranchial cysts decreased with age, while area(s) of C-cell hyperplasia appeared with age. Beginning at 56 weeks, some of the thyroid follicles were hyperdistended with colloid, had irregular lumens, and were lined by flattened epithelium. These follicles had clumped, granular, and stratified colloid. Follicular tumors were found in 8% of the males and 6% of the females at 108 weeks. There was an increase in absolute thyroid weights (males from 21.8 +/- 4.0 g to 46.5 +/- 19.05 g, females from 17.2 +/- 4.53 g to 41.7 +/- 26.92 g) and body weights (males from 382.0 +/- 70.6 g to 806.0 +/- 120.7 g, females from 220.0 +/- 21.0 g to 495.0 +/- 127.3 g) with age in both sexes, but the relative thyroid weights were not significantly affected. Negative allometry was observed. With an increase in the age of the rats, there was a decrease in the height of the follicular epithelium and an increase in the internal follicular diameter and the total number of follicles. No prediction for sex could be detected. Serum T3 and T4 concentrations were constant until 56 weeks of age, but at 108 weeks, the values were markedly reduced (in males, serum T3 concentration decreased from 91.60 +/- 13.970 ng/100 ml to 32.90 +/- 10.878 ng/100 ml, and in females, from 90.80 +/- 11.338 ng/100 ml to 48.10 +/- 8.875 ng/100 ml; in males, serum T4 concentration decreased from 5.94 +/- 0.679 microgram/100 ml to 3.04 +/- 0.604 microgram/100 ml, and in females, from 4.59 +/- 0.717 microgram/100 ml to 2.77 +/- 0.786 microgram/100 ml). The data suggest that the thyroid function of Sprague-Dawley rats reduces as the rats age.

Aging↗
PubMed1990

Morphological assessment of visual dysfunction.

The eye is an isolated unit but with a potentially high degree of sensitivity to toxic substances. The multiplicity of types of reaction to injury reflects the unique anatomical, physiological and biochemical features of the eye. The following are examples of such: The albino rat is not a good model for retinal toxicity because of problems of phototoxic retinopathy, the absence of pigment within the pigment epithelial layer and the high incidence of spontaneous retinal pathologies; The ocular toxicity of a compound cannot be anticipated from its chemical structure; Pharmacological side effects are similar between species, and are predictive for man; Mechanisms of ocular toxicity are poorly understood.

Animals↗
PubMed1989

Toxicity studies with quinine hydrochloride.

Three-month studies in the rat, a rat embryo-toxicity study and a specific study to investigate ototoxicity were carried out with quinine hydrochloride. The results of these studies suggest an acceptable daily intake of 40 mg quinine hydrochloride for an adult. There were no indications of teratogenic effects and no indications of interference with auditory function in rats receiving up to 200 mg/kg.

Animals↗
PubMed1988

The toxicology of gossypol acetic acid and (-)-gossypol.

The toxicity of gossypol has been investigated in Sprague-Dawley rats at dosages of 0, 0.5, 5.0 and 25 mg/kg per day of (+/-)-gossypol acetic acid. The most significant toxicological finding was marked suppression of body weight gain in rats receiving 25 mg/kg per day. Terminal studies showed 6 out of 20 rats receiving 25 mg/kg per day to have varying degrees of testicular pathology. Five mg/kg per day was shown to be a "no effect" level. A study in cynomolgus monkeys at 25 mg/kg per day of (+/-)-gossypol acetic acid for 13 weeks induced death, a variety of clinical signs, extensive biochemical change and pathology in the heart, liver, kidney and testes. The toxicity of (-)-gossypol was investigated in male cynomolgus monkeys at dosages of 1.5, 4 or 5 mg/kg/day for 4 weeks. No animals died. Clinical signs involving the gastrointestinal tract, adverse effects on body weight gain, consistent biochemical changes in serum proteins, calcium, inorganic phosphorus and serum cholesterol were recorded at 4 mg/kg per day and above. Morphological change was not induced.

Animals↗
PubMed1987

A report on drug-induced kerato-conjunctivitis sicca in dogs.

Kerato-conjunctivitis sicca is reported in beagle dogs treated with an antispasmodic compound for 26 weeks during a routine toxicity study. There was a deficiency of lachrymal secretion associated with keratitis and corneal vascularization. Histopathologically, the changes were characterized by vascularization, fibroblast proliferation and infiltration of inflammatory cells in the substantia propria. In some cases, the inflammation also occurred in corneal epithelium, ocular conjunctiva and corneal limbi.

Animals↗
PubMed1987

Summary of the toxicologic profile of iopentol.

Repeat dose toxicity studies, reproductive studies and mutagenicity studies were performed to assess the safety of iopentol. It is concluded that iopentol, a non-ionic contrast medium, is free from significant toxic effects.

Abnormalities, Drug-Induced↗
PubMed1986

The toxicity of gossypol to the male rat.

When (+/-) gossypol acetic acid was administered to male Sprague-Dawley rats for 26 weeks, the most significant toxicological finding was marked suppression of body weight gain in rats receiving 25 mg/kg per day. Minor biochemical changes were noted at this dosage level. Terminal studies showed 6 out of 20 rats receiving 25 mg/kg per day to have varying degrees of testicular pathology. Five mg/kg per day was shown to be a "no effect" level.

Animals↗
PubMed1986

Animal models: their use and limitations in long-term safety evaluation of fertility-regulating agents.

Animal studies are usually to predict the value of new compounds and to assess their incorporation into schemes to reduce or clarify recognized hazards. There are two assumptions, that animal models are appropriate and dose-response relationship can be derived. Such tests cannot provide definite evidence about the safety of such medical agents in man. Examples are given of data arising from studies of progestogens or oestrogens in animals in relation to clinical conditions. The scientific quality of these tests depends on the adequacy of an appropriate design, competent staff and a correct evaluation of the results.

Animals↗
PubMed1986

Age-related variations in renal structure and function in Sprague-Dawley rats.

Data from 500 male and 500 female Sprague-Dawley rats used as controls in studies performed at Huntingdon Research Centre to assess the safety of drugs were sampled at 17, 30, 56, 82, or 108 weeks of age. Plasma urea nitrogen levels remained constant, except in aged males. Aging caused increased proteinuria and decreased urinary concentrating ability, in addition to increased size, weight, and degree of cortical scarring of kidneys. Chronic progressive nephropathy, first seen histopathologically at 30 weeks of age, accounted for these changes and ultimately affected 81% of male and 44% of female rats. One-fifth of two-year-old male rats had diffuse parenchymal damage and a small number also had secondary hyperparathyroidism. Other notable changes included basophilic (often colloid-filled) cortical tubules, mononuclear cell infiltrations, parenchymal and pelvic mineralization, urothelial hyperplasia, and pyelonephritis. Miscellaneous low incidence findings included one lipomatous tumour and generalized lymphosarcoma.

Aging↗