Biomedical subjects
G Hutchison
Publications and source records attributed to G Hutchison.
Learning to live with cancer: the UK experience of a European patient education and support programme.
'Learning to Live with Cancer' is a structured education and support programme for people with cancer and their families. The UK programme, now in its third year, is based on the original American 'I Can Cope' educational package pioneered by Dr Judi Johnson. The Learning to Live with Cancer programme was developed collaboratively between Judi Johnson and Dr Gertrud Grahn, Sweden. Based on sound educational principles, it has been promoted by the European Oncology Nursing Society (EONS). The complexities of an individual's response to the diagnosis of cancer is well documented. Needs for information and support will change throughout the cancer experience. The Learning to Live with Cancer programme aims to educate patients and families in order that people gain a greater understanding and can explore ways of managing illness better. An 8-week course of 2 h each week provides opportunities for learning, sharing experiences and mutual support in meeting others undergoing a similar experience. Ongoing work, now in progress, aims to develop further Learning to Live with Cancer courses for professionals to facilitate in cancer centres throughout the UK.
Cyclosporin A abrogates the acquired immunity to cutaneous reinfection with the parapoxvirus orf virus.
The effect of cyclosporin A (CsA) on host immunity to cutaneous reinfection with the parapoxvirus orf virus was studied in 6-month-old lambs. In control reinfected animals, clinical lesions and viral replication (measured by the presence of vesicular/pustular lesions and viral antigen) in regenerating epidermal cells were at a maximum on day 4 with resolution by day 9. Lesion histology revealed recruitment of T cells, B cells and dermal dendritic cells (DDC) which increased and decreased in parallel with the clinical course of the reinfection. In animals treated with CsA (25 mg/kg/day) 1 day before and for 8 days after reinfection, more severe clinical lesions and viral replication typical of primary infections were recorded and had not resolved by 28 days following reinfection. During CsA treatment, the recruitment of T cells, B cells and DDC was inhibited. With cessation of CsA treatment there was dramatic recruitment of CD4+ T cells followed by DDC then B cells to the lesion site but rapid onset of acquired immunity was not recorded. Reverse transcription-polymerase chain reaction (RT-PCR) analysis of cytokine mRNAs from lesion biopsies showed individual sheep variations. However, interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) mRNAs were detected in the control reinfected animals on days 3 and/or 9 after reinfection but not on these days in animals undergoing treatment with CsA. In the untreated lambs there was an inexplicable lack of IL-2 and IFN-gamma mRNAs on day 6 after reinfection. Tumour necrosis factor-alpha (TNF-alpha) and vascular endothelial growth factor (VEGF) mRNAs were unaffected by CsA treatment. The data suggest that CsA abrogates acquired immunity to orf virus reinfection by targetting T-cell lymphokine production.
Bournemouth General Hospital--phase 1A.
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Studies of the pathogenesis of orf virus infection in sheep.
Damage to the skin is essential for the establishment of orf virus infection and the development of typical lesions. However, analysis of the pathogenesis of experimental lesions induced by viral challenge of mildly abraded skin, indicated that the virus does not establish in the damaged epidermis, but replicates in the cells of an underlying replacement epidermal layer derived from the walls of the wool follicles. The skin reaction consists of a cellular response with necrosis and sloughing of the affected epidermis and underlying stratum papillare of the dermis. Healing is then completed by the formation of a third epidermis derived from the deeper portions of the wool follicles. Previous cutaneous infection did not prevent reintroduction of the disease, even on the same area of skin although the lesions were less severe and persisted for a shorter period.
Oral 4-hydroxyandrostenedione, a new endocrine treatment for disseminated breast cancer.
Thirty-one post-menopausal female patients, with locally advanced or disseminated breast cancer were treated with the aromatase inhibitor 4-hydroxyandrostenedione given orally at a dose of 500 mg daily. Twenty-nine patients had assessable disease. Eight patients (28%) had objective evidence of partial response and six remain in remission 7-10 months later. A further four patients (14%) had stabilisation of disease and 11 patients (37%) had progressive disease in spite of treatment. Plasma oestradiol levels were measured throughout therapy in 16 patients and were lowered to 53% +/- 8% of baseline levels within 7 days of commencing 4-hydroxyandrostenedione. With regard to toxicity, one patient developed a transient skin rash and another patient some facial swelling. A further patient developed a transient leucopaenia and treatment was therefore discontinued. Twenty-seven of the 30 evaluable patients (90%) experienced no side effects. These results indicate that oral administration of 4-hydroxyandrostenedione is an acceptable new treatment for post-menopausal women with disseminated breast cancer.
Treatment of advanced postmenopausal breast cancer with an aromatase inhibitor, 4-hydroxyandrostenedione: phase II report.
4-Hydroxyandrostenedione (4-OHA), a potent new aromatase inhibitor, was given i.m. (500-1000 mg) to 58 patients with advanced postmenopausal breast cancer. Of 52 assessable patients 14 responded (27%), in 10 (19%) the disease stabilized, and in 28 (54%) the disease progressed. Sterile abscesses occurred at the injection site in 6 patients and painful lumps were found in a further 3 patients. Two patients developed allergic-type reactions and 4 developed lethargy, suspected to be treatment induced. Plasma estradiol levels were suppressed from a mean of 7.2 +/- 0.8 (SE) pg/ml before treatment to 2.6 +/- 0.2, 2.7 +/- 0.2, and 2.8 +/- 0.3 pg/ml after 1, 2, and greater than 4 months, respectively, of treatment and remained suppressed in patients whose disease relapsed. No significant fall in estrone levels was seen. Similarly, dehydroepiandrosterone sulfate, sex hormone binding globulin, and gonadotrophin levels were unaltered after 6 months of treatment. Plasma 4-OHA levels were measured in a radioimmunoassay for androstenedione after chromatographic separation of 4-OHA from androstenedione. Drug concentrations ranged from 0.7 to 23.2 (7.8 +/- 1.1) ng/ml after 2 months on treatment. 4-OHA is an effective drug in the management of postmenopausal patients with breast cancer and does not produce notable systemic side effects.
Route of passage of cypermethrin across the surface of sheep skin.
14C cypermethrin applied topically to the dorsal surface of sheep moved radially across the skin within the stratum corneum of the epidermis at a rate which exceeded 11 cm h-1. This spread was accompanied by some dermal infiltration which was most marked at the site of application.
Infectivity of a strain of Cryptosporidium found in the guinea-pig (Cavia porcellus) for guinea-pigs, mice and lambs.
Cryptosporidiosis was diagnosed in guinea-pigs bred by a commercial laboratory supplier on histological examination of the intestine. Oral transmission to laboratory guinea-pigs aged up to 16 weeks and to infant mice, with gut contents containing oocysts, was successful, but the organism failed to infect adult mice. From day 5 post-inoculation (pi) in guinea-pigs, infection of the ileum was associated with villous stunting and fusion, and with infiltrates of macrophages and other mononuclear cells, and eosinophils. Some guinea-pigs died; others were depressed and anorectic, with diarrhoea or watery caecal contents. Mouse infections were subclinical and caused no significant pathological changes. By contrast, a bovine Cryptosporidium isolate infected infant mice but failed to infect young guinea-pigs. Guinea-pigs and infant mice excreted oocysts in faeces after a prepatent period of 3 to 4 days. Some guinea-pigs excreted oocysts for up to 2 weeks, but excretion in mice lasted only about 4 days. Infection of guinea-pigs by contact with a contaminated environment occurred, with excretion of oocysts between 17 and 27 days after exposure. An indirect fluorescent antibody test (IFA) showed that antibody was present by day 17 pi with infected bowel contents, but none was detected in the guinea-pigs exposed to the contaminated environment. The IFA test demonstrated a serological relationship between the guinea-pig isolate and a bovine strain used to infect gnotobiotic lambs. Transmission electron microscopy of intestine from infected guinea-pigs and mice showed that more than one schizont generation occurred. The first consisted of 8 merozoite packets attached to enterocytes, but many packets of 2 or 4 merozoites of the second or subsequent generations were apparently released into the gut lumen. Fixed microgametocytes contained lipid vacuoles and had microneme-like structures in their cytoplasm. Oocysts and sporocysts were also identified, with sporulation occurring within the parasitiphorous vacuole. A sparse infection was established in 1 of 2 12-day-old specific pathogen-free lambs by day 3 pi, but no oocysts were detected in its caecal contents or those of a second lamb killed 4 days later.
Prophylactic effects of anticoccidial drugs in experimental murine cryptosporidiosis.
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Effect of anthelmintic treatment on the productivity of lambs infected with the intestinal nematode, Trichostrongylus colubriformis.
Liveweight gain, food intake, wool growth and concentration of serum constituents were measured in four groups of three-month-old lambs. Groups 1 and 2 were infected on five days each week with 2500 Trichostrongylus colubriformis larvae for 18 weeks. Group 2 lambs were treated with fenbendazole (5 mg kg-1) at week 10 and week 15. Group 3 lambs were similarly infected for 10 weeks, treated with fenbendazole, but given no further larvae. A fourth control group remained uninfected throughout the trial. All lambs were killed at week 20. Mean worm populations were 16,130, 430 and zero for groups 1, 2 and 3 respectively. Over the first 10 weeks of infection, liveweight gain was reduced by 52, 43 and 51 per cent and wool growth by 33, 28 and 27 per cent respectively, in groups 1, 2 and 3. Serum hypophosphataemia and hypoalbuminaemia occurred in all three infected groups. Between weeks 10 and 20 overall weight gain and wool growth in group 1 lambs were 44 and 46 per cent lower than the controls, whereas weight gains of group 2 and group 3 lambs were similar to or slightly higher than in the controls. However, wool growth in these two groups after treatment was only 73 to 74 per cent of control values. Serum phosphorus concentrations increased to control levels within one week of anthelmintic treatment and serum albumin concentrations by two to four weeks. The ability of group 2 lambs to improve their performance after anthelmintic treatment, in the face of continued challenge, was attributed to development of resistance to reinfection.
Epileptiform seizures during prolonged etomidate sedation.
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Effects of maternal nutrition on the initiation of secondary wool follicles in foetal sheep.
The initiation of secondary (S) wool follicles usually takes place between about 95 and 135 days of gestation. Severe underfeeding during the first half of this period did not significantly inhibit the initiation of S follicles, but severe underfeeding during the latter half of this period resulted in a significantly lower number of S follicles and this number was not increased by refeeding ewes to a high level between 132 days and term. A similar reduction in S follicle initiation was effected when ewes were moderately underfed throughout most of pregnancy, but when the ewes were refed between 120 days of gestation and term the numbers of S follicles initiated were not significantly different from those of a group of well-fed animals. It is concluded that S follicle initiation is most affected by maternal undernutrition between about 115 and 135 days of gestation.
Effect of disinfectants on survival of cryptosporidium oocysts.
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Evaluation of the effect of two aldehyde-based disinfectants on the infectivity of faecal cryptosporidia for mice.
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