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Biomedical subjects

I Campbell

Publications and source records attributed to I Campbell.

At least 19 recordsLinked to original sources

Pilot study comparing the accuracy of lymphoscintigraphy sentinel lymph node localisation with axillary node dissection in women with operable breast cancer.

AIM: To evaluate the use of lymphoscintigraphy sentinel lymph node mapping with scintillation gamma probe detection and blue dye assisted sentinel lymph node biopsy in patients with invasive breast cancer. To compare the lymph nodes detected lymphosintigraphically and at surgery for invasive breast cancer and the accuracy of sentinel node prediction of axillary status. METHODS: A prospective pilot study was performed on 36 women diagnosed with invasive breast cancer requiring axillary node dissection. Lymphoscintigraphy involving peritumoral injection of 99mTechnetium antimony sulphide or rhenium sulphur colloid was performed prior to surgery. Sentinel lymph node biopsy was then performed using gamma probe and blue dye localisation. RESULTS: Sentinel lymph nodes were identified on lymphoscintigrams in 100% of cases, and sentinel nodes located surgically in 34/36 (94.4%) of patients. All women with positive axillary lymph nodes on axillary dissection were correctly identified on sentinel node biopsy. Eight patients demonstrated internal mammary (IM) node radiocolloid uptake, one returning positive IM histology in the presence of positive axillary sentinel node metastasis. CONCLUSION: A high proportion of sentinel nodes were demonstrated by lymphoscintigraphy and were subsequently removed surgically. When internal mammary nodes are identified surgical removal should be considered. In this small series sentinel lymph node status correctly predicted axillary node status in 100% of patients for whom sentinel nodes were retrieved supporting the concept of sentinel node biopsy only for women with normal sentinel lymph nodes. Evidence from randomised trials that sentinel node based management does not compromise regional control of breast cancer or survival, is awaited.

Adult↗

Interleukin-6 promotes post-traumatic healing in the central nervous system.

The central nervous system (CNS) is an immune-privileged site where the role of immune cells and mediators in traumatic brain injury is poorly understood. Previously we have demonstrated that interleukin (IL)-6, a cytokine that acts on a wide range of tissues influencing cell growth and differentiation, is an agonist for vascular endothelial growth factor (VEGF), in in vitro vascularization assays for brain microvessel endothelial cells. In this present work we focus on the role of IL-6 in promoting tissue repair in the CNS in vivo. An aseptic cerebral injury (ACI) was created in the right parietal cortex, using both wild type (C57Bl/6J) and IL-6-deficient (C57Bl/6J-IL-6-/-) mice to study the consequences of the absence of IL-6 on the pathology of brain injuries. We monitored the immediate, early, and late responses to this traumatic injury by characterizing several histologic features in the CNS at days 1, 4, 7 and 14 following injury. Acellular necrosis, cellular infiltration, and re-vascularization were characterized in the injured tissues, and each of these histologic features was individually graded and totaled to assign a healing index. IL-6-deficient mice were found to have a comparatively slower rate of recovery and healing. Furthermore, fluorescein isothiocyanate (FITC)-dextran intravenous injection demonstrated leaky vessels in IL-6-deficient but not in wild type animals following ACI. Additionally, chronic expression of IL-6 in the CNS using transgenic GFAP-IL-6 mice resulted in more rapid healing following ACI. The accelerated tissue repair in GFAP-IL-6 transgenic animals is primarily due to extensive re-vascularization as detected by endothelial cell markers. Combined, this data suggests an important role of IL-6 in tissue repair processes following traumatic injury in the CNS.

Animals↗

Random walks on fractals and stretched exponential relaxation.

Stretched exponential relaxation [exp-(t/tau)(beta(K))] is observed in a large variety of systems but has not been explained so far. Studying random walks on percolation clusters in curved spaces whose dimensions range from 2 to 7, we show that the relaxation is accurately a stretched exponential and is directly connected to the fractal nature of these clusters. Thus we find that in each dimension the decay exponent beta(K) is related to well-known exponents of the percolation theory in the corresponding flat space. We suggest that the stretched exponential behavior observed in many complex systems (polymers, colloids, glasses...) is due to the fractal character of their configuration space.

Journal Article↗

Spousal bereavement--implications for health.

BACKGROUND: Bereavement is a potential medical problem as it has implications for health through possible associations with morbidity and mortality. OBJECTIVE: The aim of the present study was to ascertain if spousal bereavement is associated with physical and psychological parameters of illness. METHODS: A spousal bereavement register was created at a village general practice in the West Midlands of 122 spouses (4.9% of the practice population). After exclusion of 22, a sample of 100 had their medical records analysed for the periods of 12 months before and after bereavement. RESULTS: Between these two periods, the average number of consultations increased from 5.99 to 7.60 (P = 0.01), where the vast majority were for physical illness. Mean number of prescriptions increased from 8.54 to 9.15 per patient (P = 0.8) for physical illness and from 0.76 to 1.34 (P = 0.09) for psychological illness. CONCLUSION: Bereavement can be viewed as a medical problem, but this is not borne out in prescribing and so care should be taken not to over-medicalize grief.

Adaptation, Psychological↗

Modern pollen-representation of some boreal species on islands in a large lake in Canada.

Studies of pollen source areas of closed-canopy sites are contradictory. Some authors found that closed-canopy sites mainly collect local pollen while others found more distant sources. This dichotomy might stem from the use of canopies of varying degrees of closure, and from variations in the pollen productivity of the local vegetation and the background pollen rain. Here, 30 islands were used to evaluate the pollen sources of closed-canopy sites. We compared pollen with the forest inventory in three quadrat sizes: 100, 400m(2) and on the whole island. Regression analyses showed that most pollen of Picea spp., Pinus spp., and Betula spp. comes from within the 400m(2) quadrat. Abies balsamea and Thuja occidentalis showed no relationship with vegetation in any of the quadrats considered, suggesting a more regional source. Insularity and island size are important factors influencing the pollen source area; correlations were stronger on islands located 120050ha. These results suggest that closed-canopy sites on islands may be useful in stand-level vegetation history reconstruction through pollen analysis, but that caution must be exercised in separating the local and regional signals.

Journal Article↗

Adenoviral transfer of xenogeneic MHC class I gene results in loss of tumorigenicity and inhibition of tumor growth.

The immune system confers protection against a variety of pathogens and contributes to the destruction of neoplastic cells. Foreign major histocompatibility complex (MHC) protein serves as a potent stimulus to the immune system. In this report, a mouse H-2Kb gene was introduced into two poorly immunogenic tumor cell lines, a mouse colonic carcinoma cell line, MCA-26 (H-2Kd), and a rat mammalian carcinoma cell line, LN-4, in an effort to stimulate tumor rejection. Our results showed that the expression of xenogeneic MHC class I antigen completely abolished the LN-4 tumorigenicity in rats, whereas the expression of allogeneic MHC class I antigen only partially reduced the MCA-26 tumorigenicity in mice. Rats with tumor regression of LN-4/H-2Kb developed a T helper type 1-dominant response, whereas rats with LN-4 tumor growth developed a T helper type 2-dominant response. The immunized rats that experienced LN-4/H-2Kb tumor regression further developed protective immunity against a subsequent challenge of LN-4 cells. This protective immunity was mediated by the LN-4 tumor-specific cellular immune response against both the transduced and the parental LN-4 cells. Recombinant adenoviral vectors are highly efficient at in vitro and in vivo gene delivery. The LN4 cells transfected with the recombinant adenovirus AdV-H-2Kb in vitro expressed the cell surface H-2Kb molecule by fluorescence-activated cell sorter analysis. Adenovirus-mediated H-2Kb gene transfer in vivo can further significantly inhibit pre-established LN-4 tumors. Those rats with complete tumor regression further developed protective immunity against the subsequent challenge of a parental LN-4 tumor. Therefore, our study indicates that the adenovirus-mediated transfer of xenogeneic MHC class I gene may be an effective alternative to the current protocol of cancer gene therapy in which the allogeneic MHC class I gene is used.

Adenoviridae↗

Adenovirus-mediated p16INK4 gene transfer significantly suppresses human breast cancer growth.

The p16INK4 tumor suppressor gene encodes a protein that inhibits cyclin-dependent kinase 4, and its homologous deletion is common in human breast cancer. p16INK4 gene transfer has been reported to be efficacious in inducing growth inhibition of various human tumors such as brain, lung, prostate, and esophageal cancers. However, the efficiency of the p16INK4 gene with regard to growth inhibition of human breast cancer has not been studied extensively. To examine its tumor-suppressive function and its potential in breast cancer gene therapy, the wild-type p16INK4 gene was expressed in an adenovirus-mediated gene delivery system and introduced into breast cancer cell lines that do not express p16INK4 protein. Expression of the introduced p16INK4 blocked tumor cell entry into the S phase of the cell cycle, induced tumor cell apoptosis, and inhibited tumor cell proliferation both in vitro and in vivo. These results strongly suggest that p16INK4 is a tumor suppressor gene and suggest that it has potential utility in breast cancer gene therapy.

Adenoviridae↗

The utility of polysporin ointment in the eradication of methicillin-resistant Staphylococcus aureus colonization: a pilot study.

We evaluated the efficacy of an ointment containing bacitracin, polymyxin B, and gramicidin for the eradication of colonization by methicillin-resistant Staphylococcus aureus in 11 medical patients, 10 (91%) of whom had previously failed a 1-week course of topical mupirocin. Mupirocin resistance was documented in 5 (45%) of 11 patients. Successful decolonization was achieved in 9 (82%) of 11 patients (based on 2 months of follow-up).

Aged↗

The effect of the general practice registrar year on perceived skills in palliative care in the West Midlands.

OBJECTIVES: To ascertain the effect of 12 months spent as a GP registrar on perceived skills in palliative care. DESIGN: A previously validated questionnaire for use with medical undergraduates is modified and used to survey perceived skills in five aspects of providing palliative care in five different scenarios at two points during the 12-month period of general practice vocational training where no specific teaching intervention is conducted. SETTING: The West Midlands. PARTICIPANTS: 210 GP registrars. RESULTS: Perceived skill ratings were seen to significantly increase during the 12-month period, but anxiety in caring for the dying did not significantly decrease. Ratings of skills were lowest when caring for a child dying with leukaemia or a young adult dying with AIDS. In addition, other important variables which had a statistically significant influence were gender and age, but interestingly not the number of previous senior house officer (SHO) posts undertaken or whether the respondent had had formal teaching on the subject in the past. CONCLUSION: It might therefore be postulated that training as a GP registrar has an important impact on the development of perceived skills in palliative care.

Adult↗

Effect of oral rotavirus/iscom vaccines on immune responses in gnotobiotic lambs.

A comparison of the effect on the immune responses in gnotobiotic lambs was made between an iscom vaccine prepared from recombinant rotavirus VP6 protein, an inactivated rotavirus/iscom-matrix vaccine and a vaccine comprising inactivated rotavirus alone. All three vaccines induced immunological priming and some degree of protection was observed after a single oral dose. However, different immune responses were induced in response to a virulent infection. The group vaccinated with the rotavirus/iscom-matrix vaccine showed a Th2-like response characterised by rotavirus-specific antibodies and a down-regulation of IFNgamma in jejunal Peyer's patches. Both Th1-like and Th2-like immune responses were induced in the group receiving the VP6 vaccine as seen by significantly increased expressions of IFNgamma and IL-6 in the jejunal Peyer's patch together with an increased percentage of CD8+ T cells in the intestine and rotavirus-specific antibodies at mucosal surfaces. Iscom vaccines given orally have the ability to induce both Th1-like and Th2-like immune responses in a ruminant model.

Administration, Oral↗

beta-catenin mutation and expression analysis in ovarian cancer: exon 3 mutations and nuclear translocation in 16% of endometrioid tumours.

The molecular mechanisms involved in the generation of epithelial ovarian cancers are poorly understood, but evidence suggests that the different histological subtypes may arise from independent tumorigenic events. beta-Catenin is emerging as an important oncogene in the transformation of a number of epithelial cancers, and mutations have been reported in a small study of endometrioid ovarian adenocarcinomas. Mutations in the NH(2)-regulatory domain of beta-catenin stabilise the cytoplasmic levels of this protein, which promotes up-regulation of the beta-catenin-T-cell factor-lymphoid enhancer factor transcriptional complex. We report here beta-catenin (CTNNB1) exon 3 mutation analysis in 149 epithelial ovarian carcinomas. This revealed 10/63 (16%) endometrioid ovarian tumours with activating mutations of the beta-catenin gene. All mutations were missense changes within the GSK3beta consensus site, affecting serine residues at codons 33 and 37 and glycine at codon 34. Immuno-histochemical analysis identified cytoplasmic stabilisation and nuclear translocation in those endometrioid tumours with mutations. This phenotypic change was also identified in 3 other endometrioid tumours that did not have somatic mutations within exon 3 of CTNNB1. Stabilisation of the free, monomeric pool of beta-catenin and the probable resulting constitutive activation of its Tcf-associated transcriptional complex appears to be a specific oncogenic event in endometrioid ovarian adenocarcinoma.

Biological Transport↗

Report of the IDECG Working Group on the modulating effect of stressors on the upper and lower limits of lipid and carbohydrate intake. International Dietary Energy Consultative Group.

The recommended caloric intake should be increased by 2870kJ (670Kcal)/d in the exclusively breast-feeding woman. Of this increase, 10% should be ingested as protein, up to 50% as lipid and no less than 40% as carbohydrate. If weight loss is desired lipid intake can be reduced but carbohydrate intake should be maintained. Of the total energy increment 3% should be supplied by essential fatty acids (linoleic and alpha-linolenic acids) and 0.5% by n-3 fatty acids. The issue of dietary supplementation with long-chain polyunsaturated fatty acids remains for future research.

Dietary Carbohydrates↗

Lack of efficacy of oral bacitracin plus doxycycline for the eradication of stool colonization with vancomycin-resistant Enterococcus faecium.

In a prospective observational cohort study designed to assess the role of oral bacitracin solution plus doxycycline in the eradication of intestinal carriage of vancomycin-resistant Enterococcus faecium (VREF) in patients on a renal ward, rectal swab specimens were obtained from 15 treated and 24 control patients. Cultures of the rectal swabs were negative for 15 (100%) of the antibiotic-treated vs. eight (33.3%) of the untreated patients (P < .001) on day 14. However, follow-up for a mean of 127 and 130 days revealed 9 of 15 (60%) and 15 of 24 (62.5%) in the treated and untreated cohorts (P = .86), respectively, carried VREF intermittently or persistently. Quantitative VREF stool cultures in the treated cohort revealed an initial 3.1-log10/g decrease, but there was an increase to pretreatment levels at 2-4 and 5-7 weeks post-treatment (7.8 and 7.4 log10/g). Oral bacitracin and doxycycline were not efficacious in reducing the carriage of VREF beyond the 2-week interval during which they were given.

Administration, Oral↗

Use of single-frequency bioimpedance at 50 kHz to estimate total body water in patients with multiple organ failure and fluid overload.

OBJECTIVE: To investigate the relationship between single-frequency bioimpedance at 50 kHz (both total body impedance and segmental impedance) and total body water, measured using tritiated water in the presence of the severe fluid retention seen in multiple organ failure. DESIGN: Prospective, controlled study. SETTING: General intensive care unit. SUBJECTS: Twenty patients with multiple organ failure and 30 normal volunteers, of whom a subgroup of ten had total body water measured. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Total body water and total and segmental bioimpedance values at 50 kHz were measured using tritiated water and a Holtain body composition analyzer in 20 patients with multiple organ failure and in ten normal volunteers. An additional 20 normal volunteers also had segmental and total body impedance measured. There was no difference in the linear regression lines constructed for the patients and the volunteers, but the SEM in the patients (7.6 L) was four times that seen in the normal subjects (1.9 L). In a further seven patients, the impedance technique overestimated the change in total body water, deduced from acute changes in weight, by between 0% and 46% (median, 12%). In the patients, who were supine, the knee-ankle segment contributed significantly more to total body impedance than it did in the normal volunteers (42.5% vs. 34.4%; p < .001), who were upright and mobile immediately before the measurement. CONCLUSIONS: Although single-frequency bioimpedance does give an indication of total body water and change in total body water, it is neither precise nor accurate enough to be the sole guide to fluid therapy. The proportion of total impedance contributed by the knee-ankle segment, which contains relatively little water, was significantly greater in the patients than in the controls, probably reflecting better drainage of fluid from the lower limb in the supine position.

Adult↗