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Biomedical subjects

G Robinson

Publications and source records attributed to G Robinson.

At least 37 records · Page 2Linked to original sources
PubMed2003

Immunolocalization and protein expression of the alpha subunit of the large-conductance calcium-activated potassium channel in human myometrium.

Large-conductance calcium-activated potassium (BKCa) channels play an important role in the control of myometrial excitability. The aim of the present study was to determine the localization and protein expression of the alpha subunit of BKCa channels in the pregnant and parturient human uterus. An anti-alpha BKCa channel monoclonal antibody (anti-alpha(995-1113)) was used to localize and quantitate immunoreactive BKCa channel protein in myometrium of singleton term pregnant women undergoing either elective (n=26) or emergency Caesarean section following the onset of spontaneous labour (n=25). Data are presented as medians (interquartile range). Differences between groups were analysed using the Mann-Whitney U test. Immunohistochemistry studies localized the alpha subunit of the BKCa channel to the plasma membrane and the cytosol of myometrial cells with similar reaction end product in pregnant women who were or were not undergoing labour. Expression of this subunit, observed as a 125 kDa band in western blots, was significantly higher in pregnant women who were not undergoing labour (30.6% (20.3, 43.9)) than in those who were undergoing labour (15.7% (11.3, 22.4); P<0.01). Reduced BKCa alpha subunit expression in pregnant women during labour may underlie the initiation of uterine contractility during parturition.

Antibodies, Monoclonal↗
PubMed2003

Domestic ruminants as models for the elucidation of the mechanisms controlling ovarian follicle development in humans.

It is necessary to understand the basic physiology underlying the complex process of folliculogenesis to address common causes of infertility and to devise innovative strategies to increase the efficiency of assisted reproduction technologies. Availability of suitable ovarian tissue is a major constraint to research in this area in humans, and monovulatory domestic ruminants represent a physiologically relevant model to elucidate basic mechanisms before more focused clinical investigations. This paper reviews the development of several whole animal and cell culture models in ruminants that have allowed basic investigations into the endocrine and local mechanisms regulating preantral and antral follicle development in monovulatory species. Studies on preantral follicle development using the ovarian autograft model have shown, contrary to accepted dogma, that FSH may mediate the rate at which preantral follicles grow and have provided evidence to support the existence of local regulatory feedback mechanisms that influence the rate of primordial follicle initiation and preantral follicle development. Studies on the endocrine control of antral follicle development using the GnRH-antagonist model have shown that a pulsatile mode of LH delivery is not a requirement for normal patterns of follicle development and ovarian hormone secretion. Studies on the local control of somatic cell differentiation using physiological cell culture models have highlighted the essential relationship between somatic cell communication and expression of differentiative markers. We conclude that the domestic ruminant represents a valuable model system for the elucidation of the endocrine and local mechanisms controlling both early and terminal stages of follicle development in monovulatory species. The results of these investigations have direct strategic relevance within clinical medicine.

Animals↗
PubMed2002

Psychological adjustment to familial-genetic risk assessment for ovarian cancer: predictors of nonadherence to surveillance recommendations.

OBJECTIVE: To evaluate whether self-report measures of psychological distress and perceived risk were associated with nonadherence to recommended ovarian cancer surveillance. METHODS: Eighty-three patients attending the Familial Ovarian Cancer Clinic (FOCC) at Princess Margaret Hospital were assessed psychosocially prior to and during initial familial-genetic assessment and then monitored for adherence with recommended follow-up surveillance over a period of 12-18 months. The assessment protocol included an investigator-designed clinic questionnaire, the State-Trait Anxiety Inventory (STAI), Center for Epidemiologic Studies Depression Scale (CESD), Life Orientation Test (LOT), Medical Outcomes Study Social Support Survey (MOSSS), Texas Inventory of Grief, and the COPE. Nonadherence was measured in terms of unexplained absences at one or two recommended and scheduled surveillance appointments following the familial-genetic assessment. RESULTS: Univariate tests revealed a significant association between higher perception of ovarian cancer risk, as assessed immediately after the familial-genetic risk assessment in the clinic and nonadherence to physician-recommended surveillance (chi2 (2, N = 83) = 9.75, P < 0.008). Empirically based estimates of risk, conveyed by the clinic team to subjects, were not significantly associated with nonadherence (chi2 (2, N = 83) = 0.19, P = 0.91). Logistic regression analysis revealed that subjects who perceived themselves to be at high ovarian cancer risk were five times more likely to be nonadherent than participants who perceived themselves to be at low or medium ovarian cancer risk. CONCLUSIONS: These results suggest that higher self-perceived risk may predict adherence difficulties to recommended surveillance in women attending a familial-genetic risk clinic.

Adult↗
PubMed2001

Vascular endothelial growth factor is an autocrine survival factor for neuropilin-expressing breast carcinoma cells.

We identify a novel function for the vascular endothelial growth factor (VEGF) in its ability to stimulate an autocrine signaling pathway in metastatic breast carcinoma cells that is essential for their survival. Suppression of VEGF expression in metastatic cells in vitro induced their apoptosis, in addition to inhibiting the constitutively elevated phosphatidylinositol 3'-kinase activity that is characteristic of these cells and important for their survival. Hypoxia enhanced the survival of metastatic cells by increasing VEGF expression. The importance of the VEGF receptor neuropilin was indicated by the ability of a neuropilin-binding VEGF isoform to enhance breast carcinoma survival. Moreover, the expression of neuropilin in neuropilin-deficient breast carcinoma cells protected them from apoptosis. The identification of this VEGF autocrine signaling pathway has important implications for tumor metastasis and therapeutic intervention.

Apoptosis↗
PubMed2001

Prevalence of hepatitis B and C infection in a methadone clinic population: implications for hepatitis B vaccination.

AIMS: To examine the HBV and HCV markers of injecting drug users on methadone maintenance, and the feasibility of vaccination at the drug clinic. METHODS: Systematic serological testing of patients for hepatitis B and C was undertaken, and free hepatitis B vaccination was offered via arranged clinic appointments. RESULTS: Hepatitis B serology was obtained in 163 of the 220 clinic patients. 85 (52.1%) patients had evidence of hepatitis B exposure, and 3 (1.8%), of previous vaccination. Positive hepatitis B markers were associated with increasing age (p=0.004), and the duration of injecting prior to treatment (p=0.008). Hepatitis B and C serology was obtained for 153 patients, with 76 (49.7%) having evidence of dual exposure. 164 (84.1%) of 195 patients were positive for antibody to hepatitis C. Completion of the vaccine course was lower than anticipated (36.5% of HBV negative patients). CONCLUSIONS: The high rates of hepatitis B exposure in injecting drug users on methadone treatment confirm the need for hepatitis B vaccination, particularly in view of their endemic hepatitis C infection. Monitoring of this group for the development of chronic liver disease and hepatocellular carcinoma is recommended. Routine cost-free vaccination of patients on entering drug treatment, using a rapid vaccination schedule, may improve compliance.

Adult↗
PubMed2001

Hepatitis services at an injecting drug user outreach clinic.

AIMS: To provide a culturally appropriate, accessible and affordable hepatitis outreach clinic for injecting drug users, a traditionally hard-to-reach population. METHODS: The community-based clinic, a collaborative project between the Wellington Drugs and Health Development Project and Capital Coast Health, was established in Wellington in 1997. Characteristics of the first 100 injecting drug users with hepatitis C assessed through the clinic are presented. RESULTS: Of 51 patients found to be hepatitis C positive, five have received hepatitis C treatment, four at the outreach and one at a base hospital. 25 have been vaccinated for hepatitis B. The clinic has established trust and rapport with the injecting-drug-user community. CONCLUSIONS: The hepatitis outreach clinic is an innovative project, crossing the primary/secondary interface of health services provision and providing personal health services within a public health initiative. The success of this model indicates potential value in offering outreach hepatitis clinics for injecting drug users in the major cities to close a gap in health service provision.

Adult↗
PubMed2001

Bowel function and hysterectomy--a review.

Hysterectomy is the most common major gynecological operation performed in the United Kingdom and in the United States. As the operation disrupts the innervation and the intimate anatomical relationship of the pelvic organs such as the bowel and the bladder, function of these organs may be affected. Frequently women date the onset of their bowel symptoms to the time of hysterectomy, though there is no scientific evidence to support causation. Although so frequently performed little is understood of the true incidence of bowel dysfunction after a hysterectomy or the pathophysiology behind it.

Depression↗
PubMed2001

Landau-Kleffner syndrome: course and correlates with outcome.

The presenting characteristics of 18 (11 female, seven male) children with Landau-Kleffner syndrome (LKS) were studied with respect to course and outcome of their condition at a mean length of 67 (SD 46) months' follow-up. All had regression of receptive language (mean age of onset 4 years 9 months) and electrical status epilepticus in sleep (ESES). Length of ESES correlated strongly with length of period between onset of illness and onset of recovery (p<0.006) and also with eventual receptive (p<0.001) and expressive (p<0.007) language. Behaviour during the acute phase was severely affected in nine children and associated with frontal lobe discharges in awake EEGs (p<0.004). Age at onset was not correlated with outcome. All children had impaired short-term memory at follow-up. Three children had language outcome within the normal range. No child with ESES lasting longer than 36 months had normal language outcome. These data lend support for intervention in ending ESES by 36 months using multiple subpial transection (MST) if steroids are ineffective or cause unacceptable side effects.

Age of Onset↗
PubMed2001

The selective preservation of colour naming in semantic dementia.

This paper documents a series of seven patients with semantic dementia who showed a selective preservation in colour naming. This was in the context of a pervasive impairment in naming nouns across a wide range of other semantic categories. To our knowledge, this is the first series of patients with semantic dementia documenting a selective preservation of colour naming. These findings are discussed in the light of current theoretical accounts of category-specific effects and the possible contribution of imageability to this selective preservation of colours.

Aged↗
PubMed2001

Rapid identification of laboratory contamination with Mycobacterium tuberculosis using variable number tandem repeat analysis.

Compared with solid media, broth-based mycobacterial culture systems have increased sensitivity but also have higher false-positive rates due to cross-contamination. Systematic strain typing is rarely undertaken because the techniques are technically demanding and the data are difficult to organize. Variable number tandem repeat (VNTR) analysis by PCR is rapid and reproducible. The digital profile is easily manipulated in a database. We undertook a retrospective study of Mycobacterium tuberculosis isolates collected over an 18-month period following the introduction of the BACTEC MGIT 960 system. VNTR allele profiles were determined with early positive broth cultures and entered into a database with the specimen processing date and other specimen data. We found 36 distinct VNTR profiles in cultures from 144 patients. Three common VNTR profiles accounted for 45% of true-positive cases. By combining VNTR results with specimen data, we identified nine cross-contamination incidents, six of which were previously unsuspected. These nine incidents resulted in 34 false-positive cultures for 29 patients. False-positive cultures were identified for three patients who had previously been culture positive for tuberculosis and were receiving treatment. Identification of cross-contamination incidents requires careful documentation of specimen data and good communication between clinical and laboratory staff. Automated broth culture systems should be supplemented with molecular analysis to identify cross-contamination events. VNTR analysis is reproducible and provides timely results when applied to early positive broth cultures. This method should ensure that patients are not placed on unnecessary tuberculosis therapy or that cases are not falsely identified as treatment failures. In addition, areas where existing procedures may be improved can be identified.

Culture Media↗
PubMed2001

Learning preferences and learning styles: a study of Wessex general practice registrars.

BACKGROUND: Experienced trainers know that individual registrars react very differently to identical learning experiences generated during the year in practice. This divergence reflects differences in registrars' learning styles. Only one study of United Kingdom (UK) general practitioners' learning styles has been undertaken. Learning style theory predicts that matching learning preference with learning style will enhance learning. This paper researches for the first time the evidence in the setting of UK general practice. AIM: To determine, for the general practice registrars within the Wessex Region, the nature of their learning preferences and learning styles and correlations between them. DESIGN OF STUDY: A descriptive confidential postal questionnaire survey. SETTING: Fifty-seven registrars identified in the Wessex Region with a minimum experience of six months in general practice. METHOD: The questionnaire gathered demographic data (sex, age, experience in general practice, years post-registration, and postgraduate qualifications). Learning preferences were elicited using a six-point Likert scale for learning experiences. The Honey and Mumford Learning Style Questionnaire (LSQ) elicited the registrars' learning styles. A second questionnaire was sent to non-responders. RESULTS: The response rate was 74%. Registrars report that interactive learning with feedback is preferred, but more passive learning formats remain valued. A wide range of learning style scores was found. The Honey and Mumford LSQ mean scores fell within the reflector-theorist quadrant. Evidence for correlations between learning preferences and learning styles was also found, in particular for the multiple choice question and audit components of summative assessment. CONCLUSION: A wide range of registrar learning styles exists in Wessex, and initial correlations are described between learning preferences and learning styles as predicted by style theory. This work sets the stage for a shared understanding and use of learning style theory to enhance professional learning throughout a GP's career. More research is needed in this domain.

Adult↗
PubMed2000

Transforming growth factor-alpha-mediated growth pathways in human gastro-intestinal cell lines in relation to the gastrin autocrine pathway.

Epidermal growth factor (EGF) and transforming growth factor-alpha (TGF-alpha) increase transcription of the gastrin gene, and the gastrin peptide may be phosphorylated by EGF-stimulated tyrosine kinase. Our aims were to compare EGF/TGF-alpha interactions in 2 human gastro-intestinal cell lines: MGLVA1, with a strong gastrin autocrine pathway, and C170HM2, with a weak pathway. Both cell lines expressed the TGF-alpha gene. MGLVA1 expressed TGF-alpha protein as determined by immuno-cytochemistry, which was absent in C170HM2. Both cell lines expressed the same level of EGF receptors, as assessed by flow cytometry; however, MGLVA1 did not have enhanced in vitro proliferation in response to EGF or TGF-alpha, unlike C170HM2. The basal growth of MGLVA1 was inhibited by anti-sera against TGF-alpha, the EGF receptor and G17. C170HM2 was not inhibited by any of the anti-sera. Neutralisation of TGF-alpha resulted in undetectable cell-associated progastrin levels in MGLVA1 (untreated had 391.7 fmol/5 x 10(6) cells). The progastrin level of C170HM2 remained unaffected. Tyrosine kinase activity, as assessed by phosphopeptide concentration, of unstimulated MGLVA1 was 2.6 times higher than that of C170HM2 in the cell membrane fraction (0.097 compared to 0.037 microg/mg protein, p < 0.001) and 4.8 times higher in the cytosolic fraction (0.269 compared to 0.056 microg/mg protein, p < 0.05). Following treatment with EGF, the phosphopeptide concentration increased in both the membrane and cytosolic fractions of both cell lines. Tyrphostin B42, which inhibits autophosphorylation of the EGF receptor, inhibited the basal growth of MGLVA1 (IC(50) 1.3 microM) and C170HM2 (9.5 microM, p < 0.05 from MGLVA1). Herbimycin, which inhibits pp60(c-src) kinase, reduced the basal growth of MGLVA1 (0.67 microM) but not C170HM2. Immunofluorescence studies confirmed the presence of tyrosine-phosphorylated proteins and pp60(c-src) within the cytoplasm of unstimulated MGLVA1 cells. There was no specific immunofluorescence for either parameter in C170HM2 cells until after treatment with EGF.

Blotting, Southern↗
PubMed2000

Psychological adjustment to familial genetic risk assessment: differences in two longitudinal samples.

Heritable cancer risk assessment is an increasingly common method of deriving valuable information relevant to deciding on appropriate screening regimens and preventive treatments. Assessments of heritable risk typically include familial-genetic evaluation, where analyses relate family pedigree to cancer risk, and DNA testing, where analyses indicate genetic mutations associated with cancer risk (e.g., BRCA1/BRCA2 mutations) or their absence. In this paper we report on the psychological responses of women given familial-genetic evaluations for ovarian cancer risk. The baseline and 6 to 12 follow-up assessments of an initial clinic-attending cohort of 65 women are compared with the baseline and 9 to 12 follow-up assessments of a second clinic-attending cohort of 60 women. Sizeable differences were found in the prevalence of clinically significant depression in these two physician or self-referred populations, as assessed by the Center for Epidemiological Studies Depression scale and in the mean scores. Hypotheses accounting for these differences are discussed.

Adaptation, Psychological↗
PubMed2000

Competency development in public health leadership.

The professional development of public health leaders requires competency-based instruction to increase their ability to address complex and changing demands for critical services. This article reviews the development of the Leadership Competency Framework by the National Public Health Leadership Development Network and discusses its significance. After reviewing pertinent literature and existing practice-based competency frameworks, network members developed the framework through sequential use of workgroup assignments and nominal group process. The framework is being used by network members to develop and refine program competency lists and content; to compare programs; to develop needs assessments, baseline measures, and performance standards; and to evaluate educational outcomes. It is a working document, to be continually refined and evaluated to ensure its continued relevance to performance in practice. Understanding both the applications and the limits of competency frameworks is important in individual, program, and organizational assessment. Benefits of using defined competencies in designing leadership programs include the integrated and sustained development of leadership capacity and the use of technology for increased access and quality control.

Curriculum↗
PubMed2000

What are the attitudes of general practitioners towards research?

There is an urgent need for high quality primary care research to provide a firm scientific basis for a primary care-led National Health Service; however, relatively little is known about general practitioners' (GPs') stated practices and attitudes towards research. This cross-sectional questionnaire study documents the attitudes and stated practices of general practitioners towards undertaking and using research. Virtually all 249 (90%) GP responders felt that primary care research was important, while majorities expressed interest in research (61%), using research to directly influence practice (68%), and an interest in undertaking future research (53%). Perceived priorities for future primary care research are chronic illness, primary care organisation, and patient behaviour.

Adult↗
PubMed1999

In vivo gene expression profile analysis of human breast cancer progression.

The development and use of molecular-based therapy for breast cancer and other human malignancies will require a detailed molecular genetic analysis of patient tissues. The recent development of laser capture microdissection and high density cDNA arrays now provides a unique opportunity to generate gene expression profiles of cells from various stages of tumor progression as it occurs in the actual neoplastic tissue milieu. We report the combined use of laser capture microdissection and high-throughput cDNA microarrays to monitor in vivo gene expression levels in purified normal, invasive, and metastatic breast cell populations from a single patient. These in vivo gene expression profiles were verified by real-time quantitative PCR and immunohistochemistry. The combined use of laser capture microdissection and cDNA microarray analysis provides a powerful new approach to elucidate the in vivo molecular events surrounding the development and progression of breast cancer and is generally applicable to the study of malignancy.

Breast Neoplasms↗