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Biomedical subjects

C Saunders

Publications and source records attributed to C Saunders.

At least 19 recordsLinked to original sources
PubMed2001

MR imaging of the skin and nipple of the breast: differentiation between tumour recurrence and post-treatment change.

Contrast-enhanced MR imaging of the breast has been found to be valuable in the assessment of local recurrence of previously treated breast cancer. We looked specifically at the appearances of the skin and nipple of the treated breast in order to describe the appearances of post-treatment change and recurrence in this region. Thirty-nine women treated for breast cancer had MR imaging of one or both breasts reviewed retrospectively with particular attention to the nipple and skin. The skin and chest wall were assessed for patients with mastectomies. All available histology of the skin and/or nipple, obtained following MR imaging, was reviewed. In patients who did not undergo surgery following MR imaging, clinical follow-up was obtained. Six of 39 cases had nodular enhancing areas seen on MR imaging, which correlated with histology demonstrating tumour recurrence within the skin and/or nipple. Of the remaining 33 patients, changes of linear or diffuse enhancement were seen in the skin and/or nipple of 15 patients. These changes were shown to be benign post-treatment changes at surgery/biopsy in 4 cases or by clinical follow-up in the remainder. In this article we demonstrate differing patterns of contrast enhancement within the skin and nipple in recurrent breast carcinoma vs. post-treatment changes. This suggests that contrast-enhanced MR imaging of the breast may be a useful tool in differentiating tumour recurrence from post-treatment changes within the skin and nipple.

Adenocarcinoma, Mucinous↗
PubMed2001

Aortic valve replacement in geriatric patients: determinants of in-hospital mortality.

BACKGROUND: Aortic valve replacement is a common procedure in elderly patients. There has been a great deal of controversy about the risks associated with early mortality. Uncertainty of the risk associated with a small valve continues to remain controversial. This study was designed to identify the risk factors influencing early mortality and establish an accurate model for the prediction of in-hospital mortality. METHODS: One hundred eighty septuagenarians and octogenarians (58% women; mean age, 76 +/- 4.7 years) underwent primary isolated aortic valve replacement between 1986 and 1997. There was an overall mortality of 16.7% (n = 180). Patients with a body surface area less than 1.8 m2 had an in-hospital mortality of 23.2% (n = 95) compared with 8.1% (n = 74; p = 0.009) for patients with a body surface area of 1.8 m2 or more. Patients with a cardiopulmonary bypass time of less than 100 minutes experienced an early mortality of 8.9% (n = 56) compared with a 10.2% (n = 59) early mortality for patients on bypass time between 100 and 124 minutes and a 29.6% (n = 64) early mortality in patients with a pump time longer than 124 minutes (p = 0.040). RESULTS: Multivariate logistic regression analysis identified small body surface area and long cardiopulmonary bypass time as independent risk factors. A higher mortality was seen in female patients and patients receiving smaller valves. However, there was a strong correlation between small body surface area, small valve size, and female gender. CONCLUSIONS: Small body surface area and long cardiopulmonary bypass time are two independent risk factors in early mortality for elderly patients undergoing primary isolated aortic valve replacement. The use of small valves does not influence early mortality.

Aged↗
PubMed2000

Amphetamine-induced loss of human dopamine transporter activity: an internalization-dependent and cocaine-sensitive mechanism.

The dopamine transporter (DAT) is a target of amphetamine (AMPH) and cocaine. These psychostimulants attenuate DAT clearance efficiency, thereby increasing synaptic dopamine (DA) levels. Re-uptake rate is determined by the number of functional transporters at the cell surface as well as by their turnover rate. Here, we present evidence that DAT substrates, including AMPH and DA, cause internalization of human DAT, thereby reducing transport capacity. Acute treatment with AMPH reduced the maximal rate of [(3)H]DA uptake, decreased AMPH-induced currents, and significantly redistributed the immunofluorescence of an epitope-tagged DAT from the plasma membrane to the cytosol in human embryonic kidney 293 cells. Conversely, DAT inhibitors, such as cocaine, mazindol, and nomifensine, when administered with AMPH, blocked the reduction in [(3)H]DA uptake and the redistribution of DAT immunofluorescence to the cytosol. The reductions of [(3)H]DA uptake and AMPH-induced DAT internalization also were inhibited by coexpression of a dominant negative mutant of dynamin I (K44A), indicating that endocytosis modulates transport capacity, likely through a clathrin-mediated pathway. With this mechanism of regulation, acute application of AMPH would reduce DA uptake not only by direct competition for uptake, but also by reducing the available cell-surface DAT. Moreover, AMPH-induced internalization might diminish the amount of DAT available for DA efflux, thereby modulating the cytotoxic effects of elevated extracellular DA.

Amphetamine↗
PubMed2000

The evolution of palliative care.

An encounter with one patient in 1948 was the catalyst for the Hospice Movement. The challenge to undertake appropriate pain and symptom control together with experience in further listening to patients in the small number of homes especially planned for dying people, finally came together during the 1960s as the impetus for the first modern hospice which opened in 1967. Since then, palliative care has been developing worldwide and has shown that the basic principles demonstrated in those early years can be interpreted in various cultures and with different levels of resources. Symptom control by a multi-professional team backed by research and education of both professionals and public has spread both into home care and into general hospitals. The family is seen as the unit of care as it finds its own potential, searches for meaning and makes the achievements possible at the end of life.

Humans↗
PubMed2000

Diagnosis of breast cancer using elastic-scattering spectroscopy: preliminary clinical results.

We report on the first stages of a clinical study designed to test elastic-scattering spectroscopy, mediated by fiberoptic probes, for three specific clinical applications in breast-tissue diagnosis: (1) a transdermal-needle (interstitial) measurement for instant diagnosis with minimal invasiveness similar to fine-needle aspiration but with sensitivity to a larger tissue volume, (2) a hand-held diagnostic probe for use in assessing tumor/resection margins during open surgery, and (3) use of the same probe for real-time assessment of the "sentinel" node during surgery to determine the presence or absence of tumor (metastatic). Preliminary results from in vivo measurements on 31 women are encouraging. Optical spectra were measured on 72 histology sites in breast tissue, and 54 histology sites in sentinel nodes. Two different artificial intelligence methods of spectral classification were studied. Artificial neural networks yielded sensitivities of 69% and 58%, and specificities of 85% and 93%, for breast tissue and sentinel nodes, respectively. Hierarchical cluster analysis yielded sensitivities of 67% and 91%, and specificities of 79% and 77%, for breast tissue and sentinel nodes, respectively. These values are expected to improve as the data sets continue to grow and more sophisticated data preprocessing is employed. The study will enroll up to 400 patients over the next two years.

Adenocarcinoma↗
PubMed2000

Microtubule-dependent regulation of alpha(2B) adrenergic receptors in polarized MDCKII cells requires the third intracellular loop but not G protein coupling.

Previous studies in cultured, polarized Madin-Darby canine kidney II (MDCKII) renal epithelial cells have demonstrated that the apical steady-state localization and delivery of the A(1) adenosine receptor is modified by disruption of the microtubule network with colchicine, whereas the basolateral localization and trafficking of the alpha(2)-adrenergic receptors (alpha(2)AR) are not; instead, the binding capacity of the alpha(2B)AR, but not alpha(2A)AR or alpha(2C)AR subtypes, is increased in a time-dependent fashion. The present studies explore the molecular basis for this alpha(2B)AR subtype-selective phenomenon. Colchicine selectively increased alpha(2B)AR density at the cell surface, as determined by confocal microscopy, receptor binding, and surface biotinylation studies. The colchicine-induced increase in the functional density of the alpha(2B)AR requires the third intracellular loop because the alpha(2B)AR loop deletion (alpha(2B)ARtriangle upi3) mutant did not show an increased receptor density after colchicine treatment. Furthermore, the colchicine-mediated increase in alpha(2B)AR density is manifest only in polarized cells because colchicine treatment of nonpolarized MDCKII renal epithelial cells as well as simian kidney COSM6 and human embryonic kidney HEK293 cells did not effect an increase in alpha(2B)AR density. Colchicine-dependent increases in alpha(2B)AR density did not depend on functional coupling to G proteins, however, because pretreatment with pertussis toxin did not eliminate the effect of colchicine. These data indicate that microtubule-dependent regulation of alpha(2B)AR density at the basolateral surface of polarized MDCKII cells requires the third intracellular loop of alpha(2B)AR but not functional alpha(2B)AR-G protein coupling.

Animals↗
PubMed2000

[Use of food composition tables in evaluation of risk of vitamin A deficiency].

One hundred and ninety-eight 24 h-recall questionnaires from pregnant attendees of the public health services in Rio de Janeiro, Brazil, were analyzed, using 5 different Food Composition Tables. The differences in calculated intakes were as high as 88% (793 to 1494 micrograms RE). The differences were significant at the 5% level using Fishers test. The INCAP table was considered more adequate because it gives more attention to the different conversion factors for carotenoids. However, the INCAP Table does not include several foods frequently consumed in Brazil, neither does it show values for culinary preparations and industrialized foods. This study shows that there is a need to improve the tools to evaluate vitamin A intake if we wish to assess nutritional risk in populations.

Analysis of Variance↗
PubMed1999

Can cardiovascular clinical characteristics be identified and outcome models be developed from an in-patient claims database?

The objective of this study was to assess whether administrative (claims) databases can be used to assess clinical variables and predict outcome. Although administrative databases are useful for assessing resource utilization, their utility for assessing clinical information is less certain. Prospectively gathered clinical databases, however, are expensive and not widely available. The UB92 formulation of the hospital bill was used as an administrative source of data and compared with the clinical cardiovascular database at Emory University. The claims database was compared with the clinical database for 11 variables. Outcome models were developed with multivariate methods. A total of 11,883 patients who underwent catheterization (5,255 underwent percutaneous transluminal coronary angioplasty [PTCA] and 3,794 underwent coronary artery bypass surgery [CABG]) between 1991 and 1995 were included. For some variables, the claims database correlated well (diabetes, sensitivity 87%, specificity 99%), whereas for others the claims database was less accurate (peripheral vascular disease, sensitivity 20%, specificity 99%). Uncertain coding in the claims database, which can result in the same code being used for co-morbid states and severity of disease, as well as complications, limited the ability of claims to predict outcome. Clinical databases may also be limited by lack of objectivity and missing data. The utility of claims databases to assess severity of disease and co-morbid states is limited, and outcome modeling and risk assessment from claims databases may be inappropriate and spurious. Developing better data standards and less expensive methods for acquisition of clinical data is necessary for improved outcome assessment.

Cardiovascular Diseases↗
PubMed1999

Localization and trafficking of alpha2-adrenergic receptor subtypes in cells and tissues.

The three alpha2-adrenergic receptor (alpha2AR) subtypes, all of which couple to multiple effectors via Gi/Go proteins, perform various functions, including the mediation of decreases in adenylyl cyclase activity, activation of receptor-mediated K+ channels, and inhibition of voltage-gated Ca2+ channels. The alpha2ARs are polarized in many target cells, such as neurons in the peripheral and central nervous system and in intestinal and renal epithelia. Precise targeting and polarization of molecules are crucial for many physiological processes, and may confer a degree of specificity that, in the case of the adrenergic receptors, could represent a reasonable strategy by which catecholamines coordinate cellular function in a highly specific way. Receptors also redistribute in response to agonist occupancy by means of sequestration, endocytosis, recycling, or, alternatively, down-regulation (degradation). The focus of this review is to compare the similarities and differences among the three alpha2AR subtypes in terms of specificity, signaling, and trafficking. It is anticipated that a molecular understanding of receptor trafficking will lead to novel therapeutic strategies for diseases linked to aberrant adrenergic receptor function or localization.

Adrenergic Agonists↗
PubMed1999

The role of oocyte transcription, the 5'UTR, and translation repression and derepression in Drosophila gurken mRNA and protein localization.

The establishment of the major body axes of the Drosophila egg and future embryo requires strict regulation of gurken mRNA and protein localization. Here, we show that grk mRNA and protein localization is dependent on synthesis of grk transcripts in the oocyte nucleus and on RNA localization elements in the 5' portion of the transcript. We also show that gurken mRNA and protein localization is dependent on region-specific translation of gurken transcripts and identify K10 as a probable negative regulator of gurken translation.

3' Untranslated Regions↗
PubMed1999

Setting up a breast cancer family history clinic.

Breast cancer causes around 21,000 deaths per year in the UK, the vast majority of these occurring in women aged over 50 years with no genetic predisposition to the disease. Screening and symptomatic services for these women, although by no means perfect or homogeneous, have gradually improved over the last 10 years and, perhaps as a result of this, together with increased use of adjuvant systemic therapy, mortality in this group has fallen. Despite this reassuring state of affairs, media interest in the disease and patients' perception of their risk of developing breast cancer have risen. Part of this is undoubtedly due to the new scientific developments in cancer genetics and, in particular, identification of the BRCA1 gene in 1994 and BRCA2 gene shortly afterwards. These genes are dominantly inherited with up to 80% penetrance; thus, women (and occasionally men) inherit these genes and have a high lifetime risk of developing breast cancer, usually at a younger age than average and possibly of a more aggressive phenotype. Unaffected family members can now be screened and, if they prove carriers, screening for early detection and prevention strategies such as bilateral prophylactic mastectomy can be offered. Because of the high risk of ovarian cancer in BRCA1 carriers, screening or prophylactic ovariectomy may also be considered.

Adult↗
PubMed1998

Targeting of G protein-coupled receptors to the basolateral surface of polarized renal epithelial cells involves multiple, non-contiguous structural signals.

Truncations and chimeras of the alpha2A-adrenergic receptor (alpha2AAR) were evaluated to identify membrane domains responsible for its direct basolateral targeting in Madin-Darby canine kidney cells. An alpha2AAR truncation, encoding transmembrane (TM) regions 1-5, was first delivered basolaterally, but within minutes appeared apically, and at steady-state was primarily lateral in its immunocytochemical localization. A TM 1-5 truncation with the third intracellular loop revealed more intense lateral localization than for the TM 1-5 structure, consistent with the role of the third intracellular loop in alpha2AAR stabilization. Addition of TM 6-7 of A1 adenosine receptor (A1AdoR) to alpha2AARTM1-5 creates a chimera, alpha2AARTM1-5/A1AdoRTM6-7, which was first delivered apically, resulting either from loss of alpha2AAR sorting information in TM 6-7 or acquisition of apical trafficking signals within A1AdoRTM6-7. Evidence that alpha2AARTM6-7 imparts basolateral targeting information is revealed by the significant basolateral localization of the A1AdoRTM1-5/alpha2AARTM6-7 and A1AdoRTM1-5/alpha2AARTM6-7+i3 chimeras, in contrast to the dominant apical localization of A1AdoR. These results reveal that sequences within TM 1-5 and within TM 6-7 of the alpha2AAR confer basolateral targeting, providing the first evidence that alpha2AAR basolateral localization is not conferred by a single region but by non-contiguous membrane-embedded or proximal sequences.

Animals↗