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Biomedical subjects

C M Steel

Publications and source records attributed to C M Steel.

At least 37 records · Page 2Linked to original sources
PubMed1999

Factors associated with prognosis for survival and athletic use in foals with septic arthritis: 93 cases (1987-1994).

OBJECTIVE: To identify factors affecting the prognosis for survival and athletic use in foals with septic arthritis. DESIGN: Retrospective study. ANIMALS: 93 foals with septic arthritis. PROCEDURE: Medical records were reviewed to obtain clinical findings, laboratory test results, radiographic findings, treatment method, and outcome. Race records for Thoroughbreds and Standardbreds were evaluated to determine whether foals subsequently raced and whether they raced successfully. RESULTS: 43 foals had 1 affected joint, 44 foals had multiple affected joints, and number of affected joints was not recorded for 6 foals. The femoropatellar and tarsocrural joints were most commonly affected. Osteomyelitis or degenerative joint disease were detected in 59% (46/78) of foals. Failure of passive transfer, pneumonia, and enteritis were common. Foals were treated with lavage, lavage and intra-articular administration of antibiotics, lavage and arthroscopic debridement with or without partial synovectomy, or lavage and arthrotomy to debride infected bone and systemic administration of antibiotics. Seventy-three foals survived to be discharged from hospital, and approximately a third raced. Isolation of Salmonella spp from synovial fluid was associated with an unfavorable prognosis for survival and multisystem disease was associated with an unfavorable prognosis for survival and ability to race; other variables were not significantly associated with survival and ability to race. CONCLUSIONS AND CLINICAL RELEVANCE: With treatment, the prognosis for survival of foals with septic arthritis was favorable, whereas prognosis for ability to race was unfavorable. Multisystem disease, isolation of Salmonella spp from synovial fluid, involvement of multiple joints, and synovial fluid neutrophil count > or = 95% at admission may be of prognostic value.

Animals↗
PubMed1999

TGF-beta is not the principal immunosuppressive component in coagulation factor concentrates.

Coagulation factor concentrates are known to inhibit a variety of immune reactions when assessed in vitro. This study assessed the immunomodulatory activity of a wide range of coagulation factor concentrates by measuring their inhibition of PHA-stimulated lymphocyte proliferation and reduction in IL-2 secretion. The hypothesis that TGF-beta is responsible for most of these effects was tested by measuring biologically active TGF-beta and immunoreactive TGF-beta1 in the concentrates and comparing the levels recorded with immunosuppressive activity. In addition, the coagulation factors were compared directly with a standard preparation of TGF-beta in a TGF-beta-specific bioassay and in lymphocyte proliferation assays. Although there was a broad correlation between levels of total or active TGF-beta and immunosuppressive activity across all of the coagulation factors tested, individual data sets showed clear discrepancies. Implying that TGF-beta probably serves as a surrogate marker for other immunomodulatory contaminants and that neither TGF-beta nor any other single substance could account for all of the immunosuppressive activity observed. Furthermore, there was a difference of more than 100-fold in the relative potencies of coagulation factors and pure TGF-beta, when compared in immunosuppression assays, indicating that the different assays did not measure the same substance. Whereas anti-TGF-beta antibody almost completely blocked the activity of coagulation factor concentrates (TGF-beta-specific bioassay) and abrogated the effect of authentic TGF-beta (immunosuppression assays) at high concentrations it achieved <50% reversal of the immunosuppressive effects of coagulation factors in immunosuppression assays. These findings indicated that TGF-beta accounted for only a minor proportion of the immunosuppressive activity in most coagulation factor concentrates.

Animals↗
PubMed1999

Effect of topical rh-TGF-beta 1 on second intention wound healing in horses.

OBJECTIVE: To investigate the effects on wound healing of transforming growth factor-beta 1 as a topical treatment to full-thickness, excisional wounds of the distal limb of horses. DESIGN: A randomised block study using four horses, each with wounds assigned to four treatment groups. ANIMALS: Four adult Standardbred geldings. PROCEDURE: Four, 4 cm2, full-thickness wounds were created on the dorsomedial and dorsolateral aspect of the metacarpus or metatarsus of each limb of four horses, giving a total of 64 wounds. For each limb, wounds were randomly assigned to four treatment groups: no treatment (control), carrier (Methyl Cellulose gel), 50 ng/wound rhTGF-beta 1 in carrier, and 500 ng/wound rhTGF-beta 1 in carrier. Wounds were treated on day 0 and day 8. Effects of treatment were evaluated on the basis of the presence of exuberant granulation tissue requiring excision, number of times excision was required, total wound area, area of epithelialisation, area of granulation, and histological evaluation of biopsy samples of wounds on day 8 and excised wounds on day 21. RESULTS: Topical application of TGF-beta 1 at the two concentrations studied had no significant effect on the total area of wounds (P = 0.7), the area of granulation tissue (P = 0.78), the area of epithelialisation (P = 0.92), histological assessment or subjective clinical assessment of wounds. CONCLUSION: TGF-beta 1 had no beneficial effects on wound healing. Additional trials are needed to test if it has value for wound treatment in horses.

Administration, Cutaneous↗
PubMed1999

Ulceration and stricture of the right dorsal colon after phenylbutazone administration in four horses.

Four cases of ulceration and stricture of the right dorsal colon were encountered. Ulceration of the right dorsal colon is generally associated with nonsteroidal anti-inflammatory drug (NSAID) toxicosis but there are few reports of stricture following ulceration. All four horses had recent phenylbutazone use: three had been given doses well in excess of the recommended dose and in one the dose was marginally above those recommended but was combined with administration of other NSAIDs. All four horses presented with intermittent low-grade colic, weight loss and ventral oedema. Diarrhoea was also seen in three of them. All had hypoproteinaemia due to severe hypoalbuminaemia, and hyperfibrinogenaemia. Hypoalbuminaemia was less severe in one horse and this horse was successfully managed medically. Two cases were definitively diagnosed at exploratory celiotomy and two at necropsy. Exploratory celiotomy was performed in two horses: one was euthanased at surgery and one was managed successfully with medical treatment and remained normal 1 year after surgery. Medical management included feeding of a low-roughage pelleted ration, corn oil, psyllium mucilloid, and discontinuation of NSAID administration.

Animals↗
PubMed1999

Efficacy of early diagnosis and treatment in women with a family history of breast cancer. European Familial Breast Cancer Collaborative Group.

BACKGROUND: Surveillance programmes for women at increased genetic risk of breast cancer are being established worldwide but little is known of their efficacy in early detection of cancers and hence reduction in mortality. METHODS: Data were contributed from seven centres participating in the EU Demonstration Programme on Clinical Services for Familial Breast Cancer. All breast tumours (n = 161) detected prospectively, from the time of enrolment of women in a screening programme, were recorded. Analysis took account of age at diagnosis, whether tumours were screen-detected or not, their pathological stage and outcome by Kaplan-Meier survival plots. RESULTS: Mean age at diagnosis was 48.6 years. Overall, 75% of tumours were detected in the course of planned examinations. For women under age 50 at diagnosis, this figure was 68%. Eighteen percent were mammographically negative, (23% in patients under age 50). At first ("prevalence") round and at follow-up screening, 16% and 22% of tumours respectively were carcinoma in situ (CIS) while 27% and 22% respectively had evidence of nodal or distant spread (CaN+). Comparison of screen-detected and other tumours showed that the latter were more frequently mammogram-negative and CaN+. Overall five-year survival was 89% and five-year event-free survival 86%. Five-year event-free survival was 100% for CIS, 88% for invasive cancer without nodal or distant spread and 67% for CaN+. CONCLUSIONS: The majority of cancers arising in women at increased genetic risk of breast cancer can be detected by planned screening, even in those under age 50. Surveillance should include regular expert clinical examination and teaching of "breast awareness" as well as mammography. Attention to the logistics of screening programmes may improve still further the proportion of tumours that are screen-detected. The trend towards earlier pathological stage in tumours detected during follow-up rounds and the preliminary findings on survival analysis suggest that this approach will prove to be of long-term benefit for breast cancer families.

Adult↗
PubMed1998

Multifactorial analysis of differences between sporadic breast cancers and cancers involving BRCA1 and BRCA2 mutations.

BACKGROUND: We have previously demonstrated that breast cancers associated with inherited BRCA1 and BRCA2 gene mutations differ from each other in their histopathologic appearances and that each of these types differs from breast cancers in patients unselected for family history (i.e., sporadic cancers). We have now conducted a more detailed examination of cytologic and architectural features of these tumors. METHODS: Specimens of tumor tissue (5-microm-thick sections) were examined independently by two pathologists, who were unaware of the case or control subject status, for the presence of cell mitosis, lymphocytic infiltration, continuous pushing margins, and solid sheets of cancer cells; cell nuclei, cell nucleoli, cell necrosis, and cell borders were also evaluated. The resulting data were combined with previously available information on tumor type and tumor grade and further evaluated by multifactorial analysis. All statistical tests are two-sided. RESULTS: Cancers associated with BRCA1 mutations exhibited higher mitotic counts (P = .001), a greater proportion of the tumor with a continuous pushing margin (P<.0001), and more lymphocytic infiltration (P = .002) than sporadic (i.e., control) cancers. Cancers associated with BRCA2 mutations exhibited a higher score for tubule formation (fewer tubules) (P = .0002), a higher proportion of the tumor perimeter with a continuous pushing margin (P<.0001), and a lower mitotic count (P = .003) than control cancers. CONCLUSIONS: Our study has identified key features of the histologic phenotypes of breast cancers in carriers of mutant BRCA1 and BRCA2 genes. This information may improve the classification of breast cancers in individuals with a family history of the disease and may ultimately aid in the clinical management of patients.

Adult↗
PubMed1998

Current policies for surveillance and management in women at risk of breast and ovarian cancer: a survey among 16 European family cancer clinics. European Familial Breast Cancer Collaborative Group.

The recent isolation of breast cancer predisposing genes (BRCA1 and BRCA2) allows the identification of carriers within affected families. These carriers have a 50-85% risk of developing breast or ovarian cancer and need careful follow-up. The purpose of this study was to evaluate the management and screening protocols implemented in high risk families at various family cancer clinics in Europe. A questionnaire was mailed to the members of the European Familial Breast Cancer Collaborative Group (n = 30) requesting information on the following issues: indication for surveillance of breasts and ovaries, the recommended protocol, coordination of the screening examination, prophylactic surgery, the specific management of breast cancer in a mutation carrier and the use of oestrogen. 16 centres from nine countries responded. Most centres recommend surveillance of the breasts if the lifetime risk exceeds 15-20%. The surveillance protocol that is generally advised comprises monthly self breast examination, examination by a specialist every 6 months and annual mammography, all starting from an age between 25 and 35 years. Surveillance of the ovaries is recommended in BRCA1 and BRCA2-mutation carriers, in members from breast/ovarian cancer families and in some centres in 'breast cancer only' families with an early onset of breast cancer. The recommended protocol includes gynaecological examination, sonography and estimation of CA-125 at yearly intervals starting from the age 30-35 years. Prophylactic mastectomy is considered for proven mutation carriers in some centres. Most centres consider prophylactic oophorectomy in mutation carriers and some centres also consider it for members of breast/ovarian cancer families. This survey provides insight into the guidelines for surveillance and management of familial breast cancer used at various family cancer clinics in Europe; this insight may contribute to the appropriate management of these high risk women. It should be emphasised that most recommendations are based on experts' opinion rather than on any specific studies.

Adult↗
PubMed1998

Allelic imbalance at chromosome 17p13.3 (YNZ22) in breast cancer is independent of p53 mutation or p53 overexpression and is associated with poor prognosis at medium-term follow-up.

Molecular and immunohistochemical studies of genetic events on chromosome 17p were prospectively compared with conventional clinical and pathological parameters and disease behaviour at a minimum of 72 months follow-up. In a series of 91 patients with primary operable breast cancer, 37 out of 91 (41%) patients had disease relapse and 23 out of 91 (25%) had died during the follow-up period. Allelic imbalance at the YNZ22 locus (17p13.3), demonstrated in 33 out of 63 (52%) informative patients, was significantly associated with disease recurrence (P < 0.01, 2 d.f. Cox analysis) and showed a trend towards impaired survival (P = 0.08, 2 d.f. Cox analysis) after a mean follow-up of 84 months for survivors. By contrast, p53 mutation (in 10 out of 60, 17% of cancers), p53 allelic imbalance (in 23 out of 56, 41% informative patients), p53 mRNA expression (in 47 out of 87, 54% patients), p53 mRNA overexpression (in 24 out of 87, 28%) or p53 protein expression (detected in 25/76, 32%) were not associated with disease behaviour. There was no significant association between allelic imbalance at YNZ22 and any abnormality of p53 DNA, RNA or protein. Allelic imbalance at 17p13.3 (YNZ22) serves as a marker of poor prognosis in breast cancer. As yet unidentified genes on 17p13.3, distinct from and telomeric to p53, are therefore likely to be of clinical importance in breast cancer.

Adult↗
PubMed1998

The use of videotaped information in cancer genetic counselling: a randomized evaluation study.

A video of introductory information about inherited susceptibility to breast cancer was made in consultation with clinicians in four Scottish cancer family clinics. One hundred and twenty-eight women, newly referred for breast cancer risk counselling were randomized to receive the video before (n = 66) or after (n = 62) counselling. Data were collected before randomization at clinic and by postal follow-up at 1 month. The Video Before group had shorter consultations with the breast surgeon (mean = 11.8 min+/-5.4 vs 14.6+/-7.2 for the Video After group). There was no difference between the groups in the accuracy of their risk estimate after counselling, although the Video Before group scored higher for self-reported (Z= 3.65, d.f. = 1, P < 0.01) and objectively assessed understanding (Z= 2.91, d.f. = 1, P < 0.01). At 1 month follow-up, the Video Before group were less likely to underestimate their risk estimate (38% vs 18%; chi2 = 4.62, d.f. = 1, P< 0.05), but there was then no difference between the groups in subjective or objective understanding. Use of the video was not associated with increased distress (GHQ, Spielberger State Anxiety) and was associated with greater satisfaction with the information given at the clinic. This study supports the value of videotape as a method of giving information to prepare women for breast cancer risk counselling. Observations of misunderstandings and distress emphasize the video should be seen as an aid to, not a substitute, for communications at the clinic.

Adult↗
PubMed1998

PS2 mRNA expression adds prognostic information to node status for 6-year survival in breast cancer.

Expression of pS2, an oestrogen-regulated gene, has been associated with a good short-term prognosis and response to endocrine therapy. The aim of this study was to determine whether expression of mRNA for the pS2 gene in breast cancer could contribute useful information on disease behaviour and survival at medium-term follow-up. Northern blotting was used to detect pS2 messenger ribonucleic acid (mRNA) in the primary tumour tissue from each of 90 patients with breast cancer. Axillary node status was established by sampling or clearance, oestrogen receptor concentration by enzyme immunosorbant assay and follow-up was continued for at least 6 years or until death. At 83 months mean follow-up, 29 of 90 (32%) patients had recurrent disease and, of these, 18 (20%) had died from breast cancer. pS2 mRNA expression, present in 26 of 90 (29%) cancers, was associated with freedom from disease recurrence (P = 0.026) and was significantly associated with survival at a minimum of 6 years follow-up (P < 0.001). Pathological node status and tumour size were also significantly associated with disease recurrence (P < 0.001 and P = 0.002 respectively) and inversely with survival (P < 0.001 and P < 0.001 respectively). After multiple Cox regression analysis, pS2 expression was still a significant predictor of recurrence (but not survival) after adjusting for node status and tumour size; oestrogen receptor was an independent predictor of survival. The combination of node status and pS2 expression discriminated patients with particularly good prognosis (node negative, pS2 positive: no mortality at 6 years) or poor prognosis (node positive, pS2 negative; 41% mortality at 6 years). Evaluation of pS2 expression in breast cancer at diagnosis may provide additional useful prognostic information to conventional staging.

Breast Neoplasms↗
PubMed1998

Pharmacokinetics of cisapride in the horse.

The purpose of this study was to determine the pharmacokinetics and absolute bioavailability of cisapride after intravenous (i.v.) and intragastric (i.g.) administration in healthy, adult horses. Five animals received single doses of 0.1 mg/kg, 0.2 mg/kg and 0.4 mg/kg cisapride by the i.g. route in an open, randomized fashion on different occasions separated by a washout period of at least 48 h. Four of these horses were also given a single i.v. dose of 0.1 mg/kg cisapride. Jugular venous blood was collected periodically up to 24 h after dosing. Plasma cisapride concentrations were measured by high-performance liquid chromatography. There was considerable inter individual variability in pharmacokinetic parameters. The mean (SD) values for systemic clearance (CI) and steady-state volume of distribution (Vss) were 494 (43.6) mL/h/kg and 1471 (578) mL/kg, respectively. Although the rate of cisapride absorption was quite rapid, only about half the i.g. dose was absorbed systemically. The average terminal half-life (t1/2) calculated over three i.g. doses was 2.06 h and that for i.v. administration was 2.12 h. The pharmacokinetics of cisapride from 0.1 mg/kg to 0.4 mg/kg were independent of the i.g. dose.

Animals↗