Biomedical subjects
Publications and source records attributed to R Carpenter.
Muco-epidermoid carcinoma is a rare primary of the breast with previous reports of only 15 cases. As the following case report demonstrates, it can be very difficult to diagnose on aspiration cytology and a negative result should be interpreted with caution.
AIM: Following wide local excision of breast cancer approximately 25% of patients have residual disease in the tumour bed. The aim of this study was to determine whether positive bed biopsy correlated with either local recurrence or overall survival. METHOD: Following wide excision bed biopsies were taken at four separate sites from the tumour bed. Histopathological assessment of the bed biopsies was made and compared to features within the primary tumour. Patients were followed-up over a median period of 6.17 years and local recurrence and survival data documented. RESULTS: Two hundred and sixty-eight patients were included in the study and 63 had positive bed biopsies. In all, 85 patients had a recurrence of breast cancer and 69 died. Kaplan-Meier plots showed no evidence of a difference in survival between bed biopsy positive and negative patients. Bed biopsy positive patients were at greater risk of local recurrence. CONCLUSIONS: These findings suggest that positive bed biopsy is associated with an increase in local recurrence rates but has no effect on overall survival following wide excision of breast cancer.
AIMS: The impetus for optimizing outpatient provision of breast-care services has come both from the patient and management in order to reduce anxiety and make full use of scarce resources. The one-stop diagnostic clinic for the investigation of symptomatic breast lesions is a relatively recent concept with well-known service benefits. However, acceptance to the patient has not been previously investigated. RESULTS: The results of this prospective audit demonstrate a high level of patient satisfaction with the multi-disciplinary, one-stop breast clinic.
The angiotensin II type 1 (AT1) receptor is present in a wide variety of human and animal tissues, and is particularly abundant in epithelial cells. Because of this, and because it is known that tissue renin angiotensin systems (RASs) exist that have specific local functions, we investigated the expression and localisation of components of the RAS in normal and diseased breast tissue. Using a monoclonal antibody to the AT1 receptor, immunocytochemistry confirmed that the AT1 receptor was characteristically distributed in ductal epithelial cells in both normal and malignant tissue, and in most, although not all, cells in invasive tumours. Transcription of prorenin mRNA was studied by in situ hybridisation, using a DIG-ddUTP tail-labelled probe specific for the human prorenin gene. In normal tissue, and in cases of ductal carcinoma in situ, prorenin mRNA was distributed in myoepithelial cells and in a band of connective tissue cells completely surrounding the AT1-containing ductal epithelial cells. This prorenin transcribing tissue was disrupted and attenuated in invasive tumours, and in some of these, prorenin mRNA transcription could not be detected at all. Functions ascribed to the tissue RASs include regulation of mitosis and tissue modelling, as well as fluid and electrolyte transport. The results presented here strongly suggest the possibility that a tissue RAS may also be present in the breast, closely coupled to the provision of angiotensin II to the AT1 receptors in ductal epithelial cells. This mechanism is disrupted in cancer.
The extent of primary surgery for breast cancer could be tailored to the patient if previous information on the presence or absence of lymph node involvement could be reliably determined. Prospective radioimmunoscintigraphy in 29 patients with primary breast cancer that was found on screening has been undertaken with 555 MBq (15 mCi) 99mTc SM3, an Imperial Cancer Research Fund (ICRF) murine monoclonal antibody, 0.5 mg with images at 10 min and 22 h, and analysis using a change detection algorithm. Sites of significant change between the early and later images were displayed as a map of probabilities. Image-positive and -negative axillary lymph nodes were compared by histology in the 28 evaluable patients. The correct identification of the presence or absence of node involvement, even if impalpable, has been shown in 24 out of 28 patients (29 lymph node groups). Sensitivity was 90% (nine out of ten), specificity 84% (16 out of 19) and accuracy 86%. These results encourage further assessment of this technique.
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The development of reproductive organs in Antirrhinum depends on the expression of an organ identity gene, plena, in the central domain of the floral meristem. To investigate the mechanism by which plena is regulated, we have characterised three mutants in which the pattern of plena expression is altered. In polypetala mutants, expression of plena is greatly reduced, resulting in a proliferation of petals in place of reproductive organs. In addition, polypetala mutants exhibit an altered pattern of floral organ initiation, quite unlike that seen in loss-of-function plena mutants. This suggests that polypetala normally has two roles in flower development: regulation of plena and control of organ primordia formation. In fistulata mutants, plena is ectopically expressed in the distal domain of petal primordia, resulting in the production of anther-like tissue in place of petal lobes. Flowers of fistulata mutants also show a reduced rate of petal lobe growth, even in a plena mutant background. This implies that fistulata normally has two roles in the distal domain of petal primordia: inhibition of plena expression and promotion of lobe growth. A weak allele of the floral meristem identity gene, floricaula, greatly enhances the effect of fistulata on plena expression, showing that floricaula also plays a role in repression of plena in outer whorls. Taken together, these results show that genes involved in plena regulation have additional roles in the formation of organs, perhaps reflecting underlying mechanisms for coupling homeotic gene expression to morphogenesis.
The overall aerial architecture of flowering plants depends on a group of meristematic cells in the shoot apex. We demonstrate that the Arabidopsis TERMINAL FLOWER 1 gene has a unified effect on the rate of progression of the shoot apex through different developmental phases. In transgenic Arabidopsis plants which ectopically express TERMINAL FLOWER 1, both the vegetative and reproductive phases are greatly extended. As a consequence, these plants exhibit dramatic changes in their overall morphology, producing an enlarged vegetative rosette of leaves, followed by a highly branched inflorescence which eventually forms normal flowers. Activity of the floral meristem identity genes LEAFY and APETALA 1 is not directly inhibited by TERMINAL FLOWER 1, but their upregulation is markedly delayed compared to wild-type controls. These phenotypic and molecular effects complement those observed in the tfl1 mutant, where all phases are shortened. The results suggest that TERMINAL FLOWER 1 participates in a common mechanism underlying major shoot apical phase transitions, rather than there being unrelated mechanisms which regulate each specific transition during the life cycle.
BACKGROUND: Outcomes management that uses critical pathways may decrease costs while improving outcomes for patients who require prolonged mechanical ventilation. OBJECTIVE: To study the efficacy of an outcomes-managed approach to weaning patients from prolonged (more than 3 days) mechanical ventilation. METHODS: A method of multidisciplinary care delivery was designed that included an outcomes manager, a care pathway for patients receiving mechanical ventilation, and weaning protocols. Data collection consisted of three parts: a retrospective review of 124 patients who required prolonged ventilation during a 1-year period before implementation of the care model, a 6-month prospective study in which 91 patients were alternately assigned by month to an outcomes-managed approach or a non-outcomes-managed approach, and a 6-month prospective study of 90 patients in which an outcomes-managed approach without alternate-month assignment was used. RESULTS: Outcomes management had no significant effect on total duration of mechanical ventilation or length of stay in the hospital, days of mechanical ventilation without tracheostomy, days of mechanical ventilation with tracheostomy, or outcome (weaned, withdrawal from mechanical ventilation, death, or transfer without weaning). However, duration of mechanical ventilation was 1.3 days shorter, length of stay in the hospital was 2.1 days shorter, and the cost per case was $ 3341 less for patients in the outcomes-managed group than for patients in the non-outcomes-managed group. CONCLUSION: Outcomes-managed care did not have a significant effect on duration of ventilation, length of stay in the hospital, or outcome in patients receiving long-term mechanical ventilation.
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Hypertrophic cardiomyopathy (HCM) in pregnancy can result in a high incidence of maternal complications. Although echocardiography is frequently performed in pregnant women with HCM in order to confirm their hemodynamic classification, this modality has not been applied during labor and delivery in these patients. This case report documents the application of two-dimensional and Doppler echocardiography during labor and delivery in a 35-year-old woman with HCM.
Reconstruction of the female breast is becoming ever more frequently requested by patients after mastectomy for cancer. One of the least complex techniques is that of local tissue expansion with a permanent prosthesis. We present our experience and the clinical outcomes of the first 100 patients to have undergone surgery in the 4 years since the introduction of this method of breast reconstruction in our unit. A retrospective study was performed with a detailed questionnaire being sent to each patient for subjective assessment of satisfaction. Data were also collected on the rates of clinical infection of the prosthesis and the need for further surgery, including capsulotomy, nipple reconstruction and contralateral procedures. With 84% expressing their satisfaction at the final result, immediate breast reconstruction is both feasible and highly acceptable to the majority of patients.
Inflammatory pseudotumour of the orbit is an unusual condition of unknown aetiology which rarely extends beyond the orbit. To our knowledge 19 cases with intracranial extension have been reported, none of which involved the pituitary fossa or sphenoid sinus. Most required cytotoxic agents, surgery or radiotherapy in addition to corticosteroids. We present a case of orbital pseudotumour with extension into the pituitary fossa, sphenoid sinus and cavernous sinuses with vascular compression. Marked clinical improvement occurred on steroid therapy alone.
The fimbriata (fim) gene of Antirrhinum affects both the identity and arrangement of organs within the flower, and encodes a protein with an F-box motif. We show that FIM associates with a family of proteins, termed FAPs (FIM-associated proteins), that are closely related to human and yeast Skp1 proteins. These proteins form complexes with F-box-containing partners to promote protein degradation and cell cycle progression. The fap genes are expressed in inflorescence and floral meristems in a pattern that incorporates the domain of fim expression, supporting an in vivo role for a FIM-FAP complex. Analysis of a series of novel fim alleles shows that fim plays a key role in the activation of organ identity genes. In addition, fim acts in the regions between floral organs to specify the correct positioning and maintenance of morphological boundaries. Taking these results together, we propose that FIM-FAP complexes affect both gene expression and cell division, perhaps by promoting selective degradation of regulatory proteins. This may provide a mechanism by which morphological boundaries can be aligned with domains of gene expression during floral development.
Flowering plants exhibit one of two types of inflorescence architecture: indeterminate, in which the inflorescence grows indefinitely, or determinate, in which a terminal flower is produced. The indeterminate condition is thought to have evolved from the determinate many times, independently. In two mutants in distantly related species, terminal flower 1 in Arabidopsis and centroradialis in Antirrhinum, inflorescences that are normally indeterminate are converted to a determinate architecture. The Antirrhinum gene CENTRORADIALIS (CEN) and the Arabidopsis gene TERMINAL FLOWER 1 (TFL1) were shown to be homologous, which suggests that a common mechanism underlies indeterminacy in these plants. However, unlike CEN, TFL1 is also expressed during the vegetative phase, where it delays the commitment to inflorescence development and thus affects the timing of the formation of the inflorescence meristem as well as its identity.
The integrins are receptors that regulate interaction between epithelial cells and the extracellular matrix. Previous studies have shown that a reduction in the expression of the alpha2beta1, alpha3beta1, alpha6beta1, alpha(v)beta1 and alpha(v)beta5 integrins in primary breast cancer is associated with positive nodal status. In order to assess the functional significance of altered integrin expression, primary breast cancer cells were derived from individual patients with known tumour characteristics using immunomagnetic separation. Purified human fibronectin, vitronectin, laminin and type IV collagen were used to represent the principal extracellular matrix proteins in an in vitro adhesion assay. Primary breast cancer cells from lymph node-positive patients were significantly less adhesive to each of the matrix proteins studied (P<0.001, Mann-Whitney U-test). Matrix adhesion of primary breast cancer cells from node-negative patients was inhibited by appropriate integrin monoclonal antibodies (P<0.001, paired Wilcoxon test). Adhesion to fibronectin, vitronectin and laminin, but not type IV collagen, was influenced by the inhibitor arginine-glycine-aspartate, suggesting that breast cancer cell recognition of collagen IV is mediated through alternative epitopes. Weak matrix adhesion correlated with loss of integrin expression in tissue sections from corresponding patients assessed using immunohistochemistry. This study demonstrates a link between altered integrin expression and function in primary breast cancers predisposed to metastasize.
Dorsoventral asymmetry in flowers is thought to have evolved many times from a radially symmetrical ancestral condition. The first gene controlling floral asymmetry, cycloidea in Antirrhinum, has been isolated. The cycloidea gene is expressed at a very early stage in dorsal regions of floral meristems, where it affects growth rate and primordium initiation. Expression continues through to later stages in dorsal primordia to affect the asymmetry, size and cell types of petals and stamens.
Flowering plants exhibit two types of inflorescence architecture: determinate and indeterminate. The centroradialis mutation causes the normally indeterminate inflorescence of Antirrhinum to terminate in a flower. We show that centroradialis is expressed in the inflorescence apex a few days after floral induction, and interacts with the floral-meristem-identity gene floricaula to regulate flower position and morphology. The protein CEN is similar to animal proteins that associate with lipids and GTP-binding proteins. We propose a model for how different inflorescence structures may arise through the action and evolution of centroradialis.