Prevalence of scrapie in sheep in Great Britain estimated from abattoir surveys during 2002 and 2003.
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Abattoirs↗
Biomedical subjects
G Watkins
Publications and source records attributed to G Watkins.
Interleukin 7 upregulates vascular endothelial growth factor D in breast cancer cells and induces lymphangiogenesis in vivo.
BACKGROUND: Interleukin (IL) 7 is known to stimulate growth of breast cancer cells in vitro. It has been recently associated with node-positive tumours and with poor survival in breast cancer. The effects of IL-7 on the lymphangiogenic properties of breast cancer cells were explored. METHODS: The effects of IL-7 on the expression of vascular endothelial growth factors (VEGFs) in MDA MB-231, MCF-7 and BT-483 cells were analysed by reverse transcriptase-polymerase chain reaction and western blotting. An in vivo lymphangiogenesis model using nude mice was developed. The newly generated microtubules were stained with anti-von Willebrand factor and anti-LYVE-1 (lymphatic vessel endothelial hyaluronan receptor) antibodies. RESULTS: All VEGFs (VEGF-A, -B, -C and -D) were expressed in breast cancer cells, but at different levels. IL-7 increased the expression of VEGF-D at both mRNA and protein levels in MCF-7 and MDA MB-231 cells. In the in vivo model, IL-7 significantly induced the formation of lymphatic LYVE-1-positive, but not vascular von Willebrand factor-positive, microtubules (P = 0.021 versus sections without IL-7). CONCLUSION: IL-7 induced the lymphangiogenic properties of breast cancer cells, probably by upregulation of VEGF-D. This might have a significant impact on the lymphatic spread of breast cancer.
Animals↗
The Coxsackie-adenovirus receptor has elevated expression in human breast cancer.
The Coxsackie-adenovirus receptor (CAR) is the primary site for adenovirus attachment during infection and has been used as a delivery mechanism for gene therapies. However, the expression profile of the receptor in cancer, particularly in clinical breast cancer, is poorly reported. This study evaluated the expression of CAR in human breast cancers. Frozen sections from breast cancer primary tumours (matched tumour n=114 and background n=30) were immunostained with CAR antibody. RNA was reverse transcribed and analysed by quantitative-PCR (Q-PCR). Levels of CAR were analysed against the clinical background, with a median follow-up of 72 months. Staining intensity of CAR was increased within tumour sections compared to background tissue. Q-PCR revealed significantly elevated levels of CAR transcript in breast tumours (32 313+/-7067 mean+/-SE vs. background tissue 11 483+/-7069, P=0.023). CAR expression also increased with grade of tumour. Patients who had tumour metastases also showed elevated levels of CAR expression (metastasis: 61 940+/-22 749 vs. alive and well 29 655+/-8149), however those with local recurrences had reduced levels of CAR. Ductal carcinomas expressed lower levels of CAR compared to tumours of other types. Tumours with nodal involvement were also associated with higher levels of CAR (node positive 2320 median vs. node negative 1077.5). Levels of CAR were significantly correlated with long-term survival over a period of 6 years (P=0.004, univariate analysis). We conclude that CAR expression is elevated in primary breast cancers. This may have a bearing on its use as means of delivery for gene therapy and suggests that further work is necessary to understand this complex molecule.
Adenoviridae↗
Assessing microvessels and angiogenesis in human breast cancer, using VE-cadherin.
AIMS: Vascular endothelial (VE)-cadherin, also known as cadherin-5 and CD144, is an adhesion molecule uniquely expressed in endothelial cells. We hypothesized that VE-cadherin may be a useful marker for assessing microvessels and angiogenesis in human breast cancer and sought to determine whether a correlation exists between levels of VE-cadherin, angiogenic markers factor VIII and platelet endothelial cell adhesion molecule (PECAM)-1 and patient outcome in breast cancer. METHODS AND RESULTS: Frozen sections from breast cancer primary tumours (tumour n = 114, background n = 30) were immunostained with VE-cadherin, factor VIII and PECAM-1 antibodies and microvessel number was assessed. RNA was reverse transcribed and analysed by quantitative polymerase chain reaction (Q-PCR). VE-cadherin immunostaining showed a significant difference in microvessel number in tumour compared with background. There was no significant difference in the number of microvessels stained with PECAM-1 or factor VIII; there was increased staining of other structures within the sample and higher general background staining. Q-PCR revealed elevated levels of VE-cadherin and PECAM-1 in tumour samples compared with background tissue and in patients with a poor prognosis, as determined by the Nottingham Prognostic Index. There was no difference in levels with factor VIII. Both VE-cadherin and PECAM-1 had significantly reduced expression in lobular compared with ductal carcinomas: there was no difference with factor VIII. CONCLUSION: Higher levels of angiogenic marker molecules in breast cancer may have an association with poor prognosis in patients. Moreover, VE-cadherin appears to be a preferable marker for such analysis.
Antigens, CD↗
Aberrant expression of interleukin-7 (IL-7) and its signalling complex in human breast cancer.
Interleukin-7 (IL-7), a haematopoietic growth factor, is known to induce the differentiation and proliferation of some haematological malignancies including certain types of leukaemias and lymphomas. However, little is known about its role in solid tumours, including breast cancer. In this study, the expression level of IL-7, IL-7 receptor (IL-7R) and their downstream signalling molecules, including the Janus kinases (Jak-1 and Jak-3), phosphoinositide 3-kinase (PI3-K) and signal transducers and activators of transcription (Stat-5) were analysed using the reverse transcriptase-polymerase chain reaction (RT-PCR), real-time quantitative PCR and immunohistochemistry in a cohort of patients with breast cancer. The results were analysed in relation to tumour grade, TNM stage, patients' prognosis (using the Nottingham Prognostic Index (NPI)) and survival. The levels of expression of IL-7, IL-7R, Jak-1, Jak-3, PI3-K and Stat-5 were significantly higher in the most aggressive tumours. With the exception of Stat-5 expression, the transcript copies of IL-7 and all other signalling molecules were higher in patients with the worst prognoses (NPI3) and in patients who died from breast cancer after 72 months of follow-up. This aberrant expression of IL-7 and its signalling intermediates in invasive breast cancers could have significant diagnostic and prognostic implications. Measuring these molecules in breast cancer tissues may provide, for the first time, important molecular indicators of tumour differentiation, aggressiveness, nodal status, prognosis and patient survival.
Breast Neoplasms↗
Tumour endothelial marker 8 (TEM-8) in human colon cancer and its association with tumour progression.
BACKGROUND AND AIMS: Tumour endothelial marker-8 (TEM-8) is endothelial cell surface marker that may be specific to tumour endothelial cells. This study examined the role of TEM-8 in human colon cancer and its correlation with tumour prognosis. METHODOLOGY: Specimens of colorectal tissue (normal and cancer) were stained immunohistochemically with an anti-TEM-8 antibody, newly developed in our laboratory, and with anti-vonWillebrand Factor antibody. RNA was extracted from frozen sections for gene amplification. The anti-TEM-8 antibody specificity tested by using slot blotting with irrelevant antibody, and western blotting with different cell lines. The expression of TEM-8 was assessed using RT-PCR, and the level of TEM-8 was quantified using real-time-quantitative PCR (Q-RT-PCR). RESULTS: TEM-8 staining was primarily seen in endothelial cells. TEM-8 identified more micro-vessels in colon tumour tissue, than in normal colon tissues, (p=0.002). Whereas, fewer vessels were stained positive for TEM-8 in normal tissues stained positive for vonWillebrand Factor (factor-8), (p=0.008). Malignant cells in tumour tissues were found to be stained strongly positive for TEM-8 compared with the epithelial cells in normal colon tissues. The level of TEM-8 expression was significantly higher in the tumour tissues compared to the normal colon mucosa (p=0.001). TEM-8 mRNA expression was also found to be more elevated in patients with advanced tumour, Dukes C (Dukes A vs. Dukes C, p=0.01). CONCLUSION: TEM-8 is a marker that identifies tumour associated micro-vessels in colon cancer. The levels of expression of TEM-8 in invasive colon cancer are linked to disease progression. This suggests that TEM-8 has significant prognostic and therapeutic values in colon cancer.
Biomarkers, Tumor↗
The possible correlation of Notch-1 and Notch-2 with clinical outcome and tumour clinicopathological parameters in human breast cancer.
The Notch-1 and Notch-2 receptors play crucial roles in cell fate determination through interaction with the Delta/Serrate/Lag-2 family of ligands. The function of Notch signalling in tumourigenesis is still unclear, however, reports have demonstrated unregulated Notch activity in a variety of human cancers. We quantified Notch-1 and Notch-2 expression, in association with clinical outcome, in tissue samples from breast cancer patients (normal specimens n=24, breast cancer specimens n=97). We used qualitative and quantitative RT-PCR analysis, along with immunohistochemical staining to examine Notch-1 and Notch-2 expression in association with the patients clinical parameters (median follow-up 72 months). Our results show that there are aberrant levels of Notch-1 and Notch-2 in breast cancer tissues compared with normal breast tissue. Examination of the breast cancer patients' clinicopathological parameters reported that a high level of Notch-1 may be associated with a poorer outlook for the breast cancer patient, while a high level of Notch-2 correlated to a higher chance of survival. Notch-1 and Notch-2 also appear to play crucial and contrasting roles in breast tumour differentiation. Notch-1 expression was low in grade 1 tumours and increased in poorly-differentiated tumours, whereas, Notch-2 expression was high in well-differentiated tumours and reduced in breast tumours with poor differentiation. Therefore, Notch-1 may possess tumour-promoting functions, while Notch-2 could play a tumour-suppressive role in human breast cancer. These results support the notion that suppression of Notch-1 activity may represent a novel therapeutic strategy.
Base Sequence↗
[Digestive refeeding in acute pancreatitis. When and how?].
BACKGROUND: Digestive refeeding in acute pancreatitis represent a difficult issue. It requires the resolution of intestinal ileus and carries a risk of reactivation. AIM: To evaluate criteria that may guide in early refeeding avoiding unnecessary prolonged fasting. PATIENTS AND METHODS: Thirty patients with acute pancreatitis were evaluated in a prospective trial. The severity of the pancreatitis was evaluated according to APACHE II score and Balthazar CT scan alterations. The criteria proposed to start early refeeding were absence of nausea and vomiting, decreased abdominal pain, presence of bowel sounds and lowering of serum amylase levels. Balthazar CT scan classification, was used to decide between oral or enteral refeeding. RESULTS: Eighty percent of patients had alterations in pancreatic density, necrosis or pancreatic or peripancreatic liquid collections in the CT scan (corresponding to Balthazar stages C, D, or E). Ten patients fullfilled the criteria for enteral refeeding at 8.1 +/- 3.5 days (range 3 to 15 days), and 21 patients fulfilled criteria fo enteral refeeding at 8.7 +/- 4.5 (range 4-19). No patient had a reactivation of his pancreatitis. CONCLUSIONS: Digestive refeeding can be done safely by using the criteria proposed in this study. Pancreatic necrosis or peripancreatic fluid collections do not contraindicate refeeding. Oral feeding may be employed (as the first option) in selected patients, without increasing the risk of complication, regardless of CT scan alterations of the pancreas.
Acute Disease↗
[Chronic pancreatitis. A recent national experience with its surgical management].
BACKGROUND: The prevalence of chronic pancreatitis in Chile is not known and there is no local information about the surgical treatment of this disease. AIM: To review retrospectively the results of surgical treatment of chronic pancreatitis. MATERIAL AND METHODS: The charts of 17 patients (12 male), aged 7 to 65 years old, with chronic pancreatitis that were operated in three different Chilean regions, were reviewed. RESULTS: Seven patients had previous endoscopic therapeutic procedures (papillotomy in 4 and stent placing in 3). Seven patients had been subjected to previous biliary surgical procedures. Indications for surgery were severe pain in 14 patients, the suspicion of a pancreatic carcinoma in 4 patients, an infected pseudocyst in one and massive bleeding of multiple pseudo-aneurysms in a pseudocyst in one patient. Twelve patients were subjected to decompressions and 5 to pancreatic resections. There was no operative mortality and one transient pancreatic fistula. After an average follow up of 22 months, pain improved in 94% of cases, pancreatic cancer was diagnosed in one patient and 79% of subjects gained weight. One patient became insulin dependent, one increased his insulin requirements and one had transient steatorrhea, since she could not afford pancreatic enzyme replacement therapy. CONCLUSIONS: The multidisciplinary approach of patients with chronic pancreatitis, with selective use of surgery, may greatly improve their quality of life.
Adolescent↗
Day-case surgery in children under 2 years of age: experience in a district general hospital and survey of parental satisfaction.
One surgeon's experience of day-case paediatric surgery in a population aged less than 2 years at a district general hospital is reported. During a 6-year period from 1989 to 1994, 82 day-case operations were performed in 79 infants and young children. All children were managed by a multidisciplinary team including surgeon, paediatric anaesthetist and paediatric nurses. There was no mortality and minimal morbidity. A telephone survey of parents enquiring into satisfaction with all aspects of pre-, peri-, and post-operative care revealed that the procedures are well-accepted. The survey also showed that there was no increased utilization of primary health care professionals when day-case surgery is performed in this young age group. We conclude that paediatric day-case surgery is safe and well-tolerated by both infants and parents and is suitable for performance in non-specialist centres provided a team approach is adopted.
Ambulatory Surgical Procedures↗
Modified tetrachrome method for osteoid and defectively mineralized bone in paraffin sections.
A new modification of the tetrachrome method for bone osteoid in paraffin sections has been designed. The modified tetrachrome method suitable for routine use in any histology laboratory retains the simplicity of the original method and gives good results on the freshly fixed, decalcified, paraffin embedded material. Osteoid tissue is stained deep blue and normally mineralized bone is stained red. Defectively mineralized bone stains pale blue or pink and the cellular population is clearly identifiable. The ability to distinguish the osteoid tissue from mineralized bone and connective tissue and cartilage makes diagnosis of osteomalacia or osteoid producing tumors or assessment of ossification process straightforward, without the need for undecalcified sections. By displaying simultaneously irregularities in the mineralized matrix and morphology of bone cells, the method also permits the diagnosis of conditions recently described in patients with osteoporotic fractures, such as osteocytic degeneration and bone tissue defects.
Aged↗
Day-case paediatric surgery: the only choice.
Since January 1989 a policy of day-case surgery has been adopted for suitable paediatric procedures by one firm (MEF) at East Glamorgan Hospital. There have been 184 children treated to date, with an age range of 4 weeks to 13 years. There were 58 circumcisions, 48 hernias, 35 orchidopexies, 18 hydrocoeles and 25 miscellaneous procedures performed with no significant complications. All children were given a general anaesthetic, 42 procedures (22%) were performed using endotracheal intubation, the remainder with a facemask. Postoperative analgesia was provided in most cases by local wound infiltration with bupivacaine 0.25%. The average length of stay before January 1989 was 3 days and 2 nights for similar cases. Cost analysis shows significant potential financial savings of 105 pounds per patient treated. The implications for future planning are discussed.
Adolescent↗
The recalcitrant subclavian pseudoaneurysm: a case report.
A case of pseudoaneurysm of the left subclavian artery is presented. It demonstrates not only the difficulties facing the surgeon and radiologist in the management of this rare condition, but also how interventional radiology and surgery can be used in tandem to approach such a complex vascular problem.
Aged↗
Radiographic demonstration of the dislocated SC joint.
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Humans↗
Treatment of bone weakness in patients with femoral neck fracture by fluoride, calcium and vitamin D.
Twenty-three of 46 patients, aged 56 to 95 years, with fracture of the femoral neck (FNF) completed the first trial of 10 months treatment with oral sodium fluoride 60 mg and calcium 1800 mg on alternate days and 1 micrograms of vitamin D1 daily. Pre-treatment and post-treatment biopsy specimens and microradiographs of the iliac crest and metacarpal and spinal radiographs were evaluated together with biopsy material from seven untreated age-matched controls with FNF. In 17 patients the treatment improved the amount and quality of trabecular bone. Cortical thickness increased in nine patients and there were no losses of amount or mineralisation. The treatment was well tolerated by most patients and there were no major side-effects or signs of bone demineralisation. The study also revealed an unexpected rapid post-fracture deterioration of bone tissue in untreated FNF patients; thus there is an increased risk of further fractures which calls for the use of an effective treatment to increase bone mass.
Aged↗
Preventable deaths in a self-designated trauma system.
Organized paramedic care was established in 1974 in Hillsborough County, Florida, with subsequent development of a hospital self-designation system for trauma in 1980. To evaluate the level of trauma care in the county, a review of trauma deaths in 1984 was performed. A total of 452 trauma deaths was identified. Of these, 191 deaths occurred at the scene. The remaining 261 patients were transported to one of six hospitals within the county. One hundred ninety-nine subsequent deaths were attributed to central nervous system (CNS) injury, while 62 deaths were secondary to non-CNS injuries. By the method of group review, 14 (22.6%) preventable non-CNS trauma deaths were identified. Six women died and eight men died; the mean age of the deceased was 44. Ten deaths (71.4%) were secondary to blunt trauma. Mean ISS score was 21.1. Eleven deaths (79%) were due to delay to the OR, 2 deaths (14%) were due to inadequate resuscitation, and 1 death (7%) was due to lack of surgical intervention. This study demonstrates that a self-designation system without regulatory control results in a high percentage of preventable trauma deaths. We conclude that established trauma systems are needed in all areas, including those that have had organized prehospital and hospital levels of care.
Adolescent↗
Tissue mast cells in breast cancer.
The total number of mast cells and the number of such cells observed within and at the periphery of invasive breast cancers from 424 patients enrolled in protocol 4 of the National Surgical Adjuvant Breast Project were correlated with 38 other pathologic and 6 clinical features. High total mast cell counts as well as those within and at the periphery of the cancers were found to be significantly (p less than or equal to .05) associated with a patient age less than 50 years and the degree of tumor lymphoid cell reaction. The latter has also been found to be related to young age and other pathologic characteristics related to mast cell content. This suggests that the mast cells may simply represent another cell type of this reactive change. No differences in 10 year disease-free survival were detected in patients without mast cells and those exhibiting varying numbers of such cells. This information indicates that identifiable mast cells do not represent a prognostic pathologic discriminant in patients with breast cancer. However, this does not unequivocally exclude a role of mast cell secretory products, since only intact and not degranulated or disrupted forms of these cells can be counted.
Actuarial Analysis↗