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Biomedical subjects

S Sutton

Publications and source records attributed to S Sutton.

At least 19 recordsLinked to original sources
PubMed1997

Stereotactic large-gauge core biopsy: its role in the diagnosis of non-palpable mammographic abnormalities presenting to a screening service.

A retrospective study of large-gauge core biopsy (LGCB) of 206 non-palpable mammographic abnormalities detected at routine screening in a community-based clinic accredited with the Australian National Program for the Early Detection of Breast cancer, was performed to ascertain the role of LGCB as an alternative to diagnostic surgical biopsy within such a programme. Of the 51 malignancies diagnosed by LGCB and proceeding to treatment, no false-positives were found and agreement as to the presence, or otherwise, of invasion between core and open biopsy was 95%. Once malignancy was established by LGCB, one-stage treatment was possible in 74.5% of cases. A total of 114 lesions were considered to be benign and returned to routine screening. One interval cancer subsequently developed in this group. Incongruity between the pathological diagnosis from core biopsy and the mammographic image occurred in 29 cases, representing potential mistargeting in 14.1% of cases. Four cancers were discovered in this group when the patients subsequently proceeded to surgical biopsy, making an overall false-negative rate of 2.4%. No core biopsy sample was considered inadequate for pathological assessment and no lesion proved inaccessible to targeting. There was no long-term morbidity. We believe that LGCB is a safe, reliable and cheaper alternative to diagnostic surgical biopsy, but a close correlation of pathology and mammography is required to avoid the erroneous return of women to routine recall.

Biopsy, Needle↗
PubMed1996

Characterization of a sheep brain corticotropin releasing factor binding protein.

We report here the identification, purification and cDNA cloning of a corticotropin releasing factor (CRF) binding protein(s) (CRF-BP) from sheep brain. Native sheep and rat brain CRF-BP and recombinant rat CRF-BP were shown to be N-glycosylated. Two membrane associated forms of brain CRF-BPs of 33 and 35 kDa were purified from sheep brain homogenates after solubilization in the presence of detergent. N-Terminal sequence analysis revealed that the 35 kDa protein is proteolytically cleaved near the N-terminus giving rise to an 18 amino acid peptide and a 33 kDa CRF-BP. Both the purified 33 and 35 kDa ovine CRF-BPs could be specifically cross linked to ovine [125I]CRF and human [125I]CRF. In contrast, recombinant rat CRF-BP can only be cross-linked to human [125I]CRF. A 1.7 kb cDNA clone (Basil 7) encoding an open reading frame for a 324 amino acid CRF-BP precursor was cloned from a sheep brain lambda gtlO cDNA library and was shown to have 85% and 87% amino acid homology to the rat and human proteins, respectively. Competitive binding analysis of the recombinant sheep CRF-BP (Basil 7) expressed in CHO cells revealed that it binds human and ovine CRF with high affinity. However, the recombinant sheep CRF-BP (Basil 7) had approximately 50-fold higher affinity for human CRF than for the ovine peptide. These data present the first biochemical proof that CRF-BP is in the brain and provides evidence for the existence of different forms of CRF-BP which have evolved across species to regulate CRF.

Amino Acid Sequence↗
PubMed1996

Diagnostic accuracy of stereotactic core biopsy in a mammographic breast cancer screening programme.

Stereotactic core biopsy was performed on 200 women for 206 mammographically suspicious non-palpable lesions detected over a period of 2 years as part of the Australian national programme for early detection of breast cancer. This study aimed to assess the reliability of stereotactic core biopsy in this context and to develop a protocol for the evaluation of stereotactic core biopsy in mammographically detected non-palpable breast lesions. Fifty-one of 52 malignant lesions found by stereotactic core biopsy were confirmed by excision biopsy (one women declined excision). Nine (4.5%) women had atypical ductal hyperplasia on stereotactic core biopsy; at excision, six were low grade carcinomas (in situ or invasive carcinomas), one was a 3 mm focus of grade 3 invasive duct carcinoma, one was atypical ductal hyperplasia, and one patient refused excision biopsy. In 29 (14.5%) women the histology of the stereotactic core biopsy was considered not to correlate with the radiological abnormality, and excision biopsy was advised: in four of these women carcinomas were found. One hundred and ten (55%) women had 116 benign lesions on stereotactic core biopsy: on follow-up, one of these patients has been found to have a carcinoma. Core biopsy number and sequence were analysed demonstrating that no particular biopsy was more diagnostic than any other, and that the diagnostic yield of three cores was statistically equal to that of five cores. The procedure was well-tolerated and there were few complications. Thus, stereotactic core biopsy is an accurate and safe method for diagnosis of mammographically detected non-palpable breast lesions, and we believe it is the diagnostic technique of choice in breast cancer screening programmes. However, a stereotactic core biopsy diagnosis of atypical ductal hyperplasia requires excision biopsy since a diagnosis of low grade intraduct carcinoma cannot be excluded. Furthermore, if tissue obtained by stereotactic core biopsy does not correlate with the mammographic abnormality, excision biopsy should be performed.

Adult↗
PubMed1996

Histological precision of stereotactic core biopsy in diagnosis of malignant and premalignant breast lesions.

The reliability of stereotactic core biopsy in the diagnosis of malignant and premalignant breast lesions was assessed in comparison to excision biopsy in patients with non-palpable suspicious breast lesions detected in a mammography breast screening programme. Fifty-two cases of malignancy and nine of atypical ductal hyperplasia were diagnosed on the programme during the two year period July 1993 to June 1995; two patients did not have excision biopsy. Stereotactic core biopsies and representative sections from 59 excision specimens from the same patients were assessed "blind' by one pathologist. All 51 cancers diagnosed on stereotactic core biopsy were confirmed to be malignant on excision biopsy. There was 96% concordance between stereotactic core biopsy and excision biopsy for the diagnosis of invasive or in situ cancer, and 78% concordance for the type of cancer. The stereotactic core biopsy and excision biopsy diagnoses were: invasive ductal carcinomas (39 on stereotactic core biopsy vs. 33 on excision biopsy), mucinous carcinomas (1 vs. 2), invasive lobular carcinomas (3 vs, 8), and in situ carcinomas (8 vs. 8), two of which had invasive cancer present only in the stereotactic core biopsy. Of the nine cases of atypical ductal hyperplasia diagnosed on stereotactic core biopsy, eight had an excision biopsy, six showed low nuclear grade in situ or invasive cancer, one had a 3 mm focus of high grade invasive ductal cancer and one was atypical ductal hyperplasia. In the invasive ductal carcinoma group stereotactic core biopsy underestimated tumour grade: In nine cases (31%) the cancer at excision was of a higher grade. Stereotactic core biopsy is a reliable alternative to excision biopsy in the diagnosis of breast cancer, however, stereotactic core biopsy may underestimate tumour grade in invasive ductal carcinoma and may not differentiate between invasive ductal carcinoma and lobular carcinoma. It is recommended that the diagnosis of atypical ductal hyperplasia on stereotactic core biopsy be followed by excision biopsy, as stereotactic core biopsy underestimates the presence of cancer in this group.

Adult↗
PubMed1996

Nature of ligand affinity and dimerization of corticotrophin-releasing factor-binding protein may be detected by circular dichroism.

As the association of corticotrophin-releasing factor (CRF) with its binding protein (BP) to form a dimer complex (CRF2/BP2) appears to be dependent on the nature of the ligand we have compared the circular dichroism difference spectra after association of the BP with ovine (o) CRF, human (h) CRF and the alpha-helical CRF (9-41) antagonist. All three ligands caused a negative change in molar ellipticity above 210 nm, with oCRF having the least and hCRF the greatest effect. Below 210 nm there was a marked divergence of difference spectra, with the reaction with the natural peptides, hCRF and oCRF, resulting in a positive change in ellipticity, whilst that with the antagonist produced a negative change. In view of the BP spectrum indicating predominantly beta-sheet and the peptides showing mainly alpha-helix these results were interpreted as the changes above 210 nm being due to dimerization and below 210 nm to a change in the conformation of ligand on binding. The opposite change in alpha-helicity of the antagonist observed on binding compared with the two natural CRF peptides could have fundamental pharmacological implications.

Animals↗
PubMed1995

Urocortin, a mammalian neuropeptide related to fish urotensin I and to corticotropin-releasing factor.

Corticotropin-releasing factor (CRF), a peptide first isolated from mammalian brain, is critical in the regulation of the pituitary-adrenal axis, and in complementary stress-related endocrine, autonomic and behavioural responses. Fish urotensin I and amphibian sauvagine were considered to be homologues of CRF until peptides even more closely related to CRF were identified in these same vertebrate classes. We have characterized another mammalian member of the CRF family and have localized its urotensin-like immunoreactivity to, and cloned related complementary DNAs from, a discrete rat midbrain region. The deduced protein encodes a peptide that we name urocortin, which is related to urotensin (63% sequence identity) and CRF (45% sequence identity). Synthetic urocortin evokes secretion of adrenocorticotropic hormone (ACTH) both in vitro and in vivo and binds and activates transfected type-1 CRF receptors, the subtype expressed by pituitary corticotropes. The coincidence of urotensin-like immunoreactivity with type-2 CRF receptors in brain, and our observation that urocortin is more potent than CRF at binding and activating type-2 CRF receptors, as well as at inducing c-Fos (an index of cellular activation) in regions enriched in type-2 CRF receptors, indicate that this new peptide could be an endogenous ligand for type-2 CRF receptors.

Adrenocorticotropic Hormone↗
PubMed1995

Potent, structurally constrained agonists and competitive antagonists of corticotropin-releasing factor.

Predictive methods, physicochemical measurements, and structure activity relationship studies suggest that corticotropin-releasing factor (CRF; corticoliberin), its family members, and competitive antagonists (resulting from N-terminal deletions) usually assume an alpha-helical conformation when interacting with the CRF receptor(s). To test this hypothesis further, we have scanned the whole sequence of the CRF antagonist [D-Phe12,Nle21,38]r/hCRF-(12-41) (r/hCRF, rat/human CRF; Nle, norleucine) with an i-(i + 3) bridge consisting of the Glu-Xaa-Xaa-Lys scaffold. We have found astressin [cyclo(30-33)[D-Phe12,Nle21,38,Glu30,Lys33]r/ hCRF(12-41)] to be approximately 30 times more potent than [D-Phe12,Nle21,38]r/hCRF-(12-41), our present standard, and 300 times more potent than the corresponding linear analog in an in vitro pituitary cell culture assay. Astressin has low affinity for the CRF binding protein and high affinity (Ki = 2 nM) for the cloned pituitary receptor. Radioiodinated [D-125I-Tyr12]astressin was found to be a reliable ligand for binding assays. In vivo, astressin is significantly more potent than any previously tested antagonist in reducing hypophyseal corticotropin (ACTH) secretion in stressed or adrenalectomized rats. The cyclo(30-33)[Ac-Pro4,D-Phe12,Nle21,38,Glu30,Lys33++ +]r/hCRF-(4-41) agonist and its linear analog are nearly equipotent, while the antagonist astressin and its linear form vary greatly in their potencies. This suggests that the lactam cyclization reinstates a structural constraint in the antagonists that is normally induced by the N terminus of the agonist.

Adrenalectomy↗
PubMed1995

Does routine screening for breast cancer raise anxiety? Results from a three wave prospective study in England.

OBJECTIVE: To investigate whether mammography raises anxiety in routinely screened women who receive a negative result. DESIGN: Prospective design in which women completed questionnaires at three key points in the breast screening process: at baseline (before being sent their invitation for breast screening), at the screening clinic immediately before or after screening, and at follow up, about nine months after baseline. Information was obtained from non-attenders as well as from attenders. SETTING: Bromley District Health Authority, served by the South East London Breast Screening Service. PARTICIPANTS: Two overlapping samples were used. Sample A comprised 1500 women aged 50-64 who were due to be called for first round screening at a mobile screening unit. Altogether 1021 (68%) returned a usable questionnaire and 795 of these (78%) also provided adequate information at nine month follow up: there were 695 attenders (including 24 women who received false positive results) and 100 non-attenders. Sample B consisted of 868 women who attended the screening unit in a three month period, 732 (84%) of whom provided adequate data. A total of 306 attenders (including 10 who received false positive results) occurred in both samples and provided adequate information on all occasions. The main analyses were based on these 306 women plus the 100 non-attenders. The analysis of retrospective anxiety took advantage of the larger sample size of 695 attenders. MAIN RESULTS: On average, the women were not unduly anxious at any of the three points in the screening process. Among attenders, there was no difference between anxiety levels immediately before and immediately after screening. Anxiety was lowest at the clinic and highest at baseline but the changes were very small in absolute terms. Anxiety did not predict attendance: there were no differences in anxiety levels between attenders and non-attenders at baseline. As expected, women who received false positive results recalled feeling extremely anxious after they had received the referral letter but their retrospective anxiety was also higher than in the negative screenees at earlier stages in the breast screening process. They also reported having experienced more pain and discomfort during the x ray. CONCLUSIONS: Anxiety does not seem to be an important problem in routinely screened women who receive a negative result. This finding is very reassuring in relation to a major criticism of breast screening programmes. Thus, apart from maintaining current procedures such as keeping waiting times to a minimum, there seems to be no need to introduce special anxiety reducing interventions into the national programme. On the other hand, the findings for women who received false positive results suggest that there are aspects of the experience of being recalled for assessment after an abnormal mammogram that warrant further attention. The relationship between contemporaneous and retrospective anxiety should also be studied.

Anxiety↗
PubMed1995

Marked changes of arginine vasopressin, oxytocin, and corticotropin-releasing hormone in hypophysial portal plasma after pituitary stalk damage in the rat.

Mechanical compression of the pituitary stalk with the help of a blunt stereotaxic knife results in posterior pituitary denervation (PPD) and sprouting proximal to the injury, leading to formation of an ectopic neurohypophysis in the stalk. This provides an experimental model for those cases in which traumatic damage severs the nerve fibers to the neural lobe but does not obliterate the hypophysial-portal circulation. The effect of PPD on the hypophysial-portal concentration profile of putative ACTH secretagogues as well as basal and stimulated ACTH secretion in vitro were investigated at varying times after PPD. The contents of arginine vasopressin (AVP) and oxytocin (OT) in extracts of the stalk median eminence 1 week after PPD were markedly elevated, whereas corticotropin-releasing hormone (CRH) content was unaffected. Levels of these three neuropeptides in hypophysial-portal blood collected under anesthesia from the proximal stump of the transected stalk (or the ectopic neural lobe) were measured at weekly intervals in groups of rats after sham or PPD surgery. Hypophysial-portal AVP levels showed a monotonic increase with time after PPD from a 1.8-fold elevation at 1 week post-PPD to a maximum concentration 6-fold greater than that in sham groups at 4 weeks post-PPD. Portal plasma OT levels also exhibited extreme elevation. In contrast, portal plasma CRH levels showed an initial 72% decline 1 week post-PPD. We suggest that mechanical damage to the pituitary stalk and the subsequent sprouting redirected secretion of AVP and OT from the neural lobe to the pituitary stalk. This caused sustained elevations of portal plasma concentrations of AVP and OT. The resulting tonic exposure to AVP and/or OT may down-regulate anterior pituitary receptors to these neurohypophyseal peptides and indirectly decrease CRH release into the portal circulation.

Adrenocorticotropic Hormone↗
PubMed1994

Distribution of corticotropin-releasing factor receptor mRNA expression in the rat brain and pituitary.

Corticotropin-releasing factor (CRF) is a major hypophysiotropic peptide regulating pituitary-adrenal response to stress, and it is also widely expressed in the central nervous system. The recent cloning of cDNAs encoding the human and rat CRF receptors has enabled us to map the distribution of cells expressing CRF receptor mRNA in rat brain and pituitary by in situ hybridization. Receptor expression in the forebrain is dominated by widespread signal throughout all areas of the neo-, olfactory, and hippocampal cortices. Other prominent sites of CRF receptor mRNA expression include subcortical limbic structures in the septal region and amygdala. In the diencephalon, low levels of expression are seen in a few discrete ventral thalamic and medial hypothalamic nuclei. CRF receptor expression in hypothalamic neurosecretory structures, including the paraventricular nucleus and median eminence, is generally low. In the brainstem, certain relay nuclei associated with the somatic (including trigeminal), auditory, vestibular, and visceral sensory systems, constituted prominent sites of CRF receptor mRNA expression. In addition, high levels of this transcript are present in the cerebellar cortex and deep nuclei, along with many precerebellar nuclei. In the pituitary, moderate levels of CRF receptor mRNA expression were detected throughout the intermediate lobe and in a subset of cells in the anterior lobe identified as corticotropes by concurrent immunolabeling. Overall, the central distribution of CRF receptor mRNA expression is similar to, though more expansive than, that of regions reported to bind CRF, and it shows limited overlap with loci expressing CRF-binding protein. Interestingly, CRF receptor mRNA is low or undetectable in several cell groups implicated as central sites of CRF action.

Adrenocorticotropic Hormone↗
PubMed1994

Profound atrophy of the bone marrow reflecting major histocompatibility complex class II-restricted destruction of stem cells by CD4+ cells.

The effector functions of CD4+ cells in vivo are presumed to reflect a combination of lymphokine-mediated bystander reactions and direct cytotoxic T lymphocyte activity. To assess the relative importance of these two mechanisms, we studied the effects of transferring small doses of purified unprimed CD4+ cells to lightly irradiated (600 cGy) recipients expressing major histocompatibility complex class II (Ia) differences. Within the first week after transfer, the host marrow was rapidly repopulated with hemopoietic cells. Thereafter, however, the donor CD4+ cells caused massive destruction of hemopoietic cells, both in marrow and spleen. Marrow aplasia did not affect stromal cells and was prevented by coinjecting donor but not host bone marrow. The use of allotypic markers and fluorescence-activated cell sorter analysis indicated that the destructive effects of CD4+ cells were directed selectively to host Ia+ hemopoietic cells, including stem cells; donor hemopoietic cells and Ia- host T cells were spared. No evidence could be found that the ongoing destruction of host cells impaired the capacity of donor stem cells to repopulate marrow, spleen, or thymus. Moreover, CD4+ cells failed to destroy host-type hemopoietic cells from Ia-deficient mice. Tissue destruction by CD4+ cells thus did not seem to reflect a bystander reaction. We conclude that, under defined conditions, CD4+ cells can manifest extremely potent Ia-restricted CTL activity in vivo, probably through recognition of covert Ia expression on stem cells and/or their immediate progeny.

Animals↗
PubMed1994

Anxiety and self-esteem as a function of abstinence time among recovering addicts attending Narcotics Anonymous.

Among 200 members of Narcotics Anonymous (NA), those who had been off drugs and in contact with NA for longer tended to have lower trait anxiety and higher self-esteem scores, the relationship in each case being approximately linear. Those abstinent for longer than about three years had levels of anxiety and self-esteem similar to those in a comparison group of 60 students.

Adult↗
PubMed1994

Prospective study of predictors of attendance for breast screening in inner London.

OBJECTIVE: To investigate the predictors of first-round attendance for breast screening in an inner city area. DESIGN: Prospective design in which women were interviewed or completed a postal questionnaire before being sent their invitation for breast screening. Sociodemographic factors, health behaviours, and attitudes, beliefs, and intentions were used as predictors of subsequent attendance. A randomised control group was included to assess the effect of being interviewed on attendance. SETTING: Three neighbouring health districts in inner south east London. PARTICIPANTS: A total of 3291 women aged 50-64 years who were due to be called for breast screening for the first time. The analysis of predictors was based on a subsample of 1301, reflecting a response rate of 75% to interview and 36% to postal questionnaire. MAIN RESULTS: Attendance was 42% overall, and 70% in those who gave an interview or returned a questionnaire. There was little evidence for an interview effect on attendance. The main findings from the analysis of predictors are listed below. (These were necessarily based on those women who responded to interview/questionnaire and so may not be generalisable to the full sample.) (1) Sociodemographic factors: Women in rented accommodation were less likely to go for screening but other indicators of social class and education were not predictive of attendance. Age and other risk factors for breast cancer were unrelated to attendance, as was the distance between home and the screening centre. Married or single women were more likely to attend than divorced, separated, or widowed women, and black women had a higher than average attendance rate; however, neither of these relationships was found in the interview sample. (2) Health behaviours: Attenders were less likely to have had a recent breast screen, more likely to have had a cervical smear, more likely to go to the dentist for check ups, and differed from non-attenders with regard to drinking frequency. Exercise, smoking, diet change, and breast self-examination were unrelated to attendance. (3) Attitudes, beliefs, and intentions: The two best predictors were measures of the perceived importance of regular screening for cervical and breast cancer and intentions to go for breast screening. Also predictive were beliefs about the following: the personal consequences of going for breast screening, the effectiveness of breast screening, the chances of getting breast cancer, and the attitudes of significant others (the woman's husband/partner and children). Women who reported a moderate amount of worry about breast cancer were more likely to attend than those at the two extremes. CONCLUSIONS: Attenders and non-attenders differ in two broad areas: the health related behaviours they engage in and the attitudes, beliefs, and intentions they have towards breast cancer and breast screening. The latter are potentially amenable to change, and though different factors may operate among women who do not respond to questionnaires, the findings offer hope that attendance rates can be improved by targeting the relevant attitudes and beliefs. This could be done by changing the invitation letter and its accompanying literature, through national and local publicity campaigns, and by advice given by GPs, practice nurses, and other health professionals. It is essential that such interventions are properly evaluated, preferably in randomised controlled studies.

Attitude to Health↗