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Biomedical subjects

P Crowe

Publications and source records attributed to P Crowe.

At least 19 recordsLinked to original sources

Metallothionein crypt-restricted immunopositivity indices (MTCRII) correlate with aberrant crypt foci (ACF) in mouse colon.

Metallothionein (MT) crypt-restricted immunopositivity indices (MTCRII) are colonic crypt stem cell mutation markers that may be induced early and in abundance after mutagen treatment. Metallothionein is the endogenous reporter gene for MTCRII, but is not typically implicated in the classical pathway of colorectal tumorigenesis. Hence, the oncological relevance of MTCRII is unclear. This study tests the hypothesis that MTCRII induced by N-methyl-N-nitrosourea (MNU) and lambda carrageenan (lambdaCgN) associate with aberrant crypt foci (ACF) in mouse colon. Undegraded lambdaCgN and MNU were tested alone and in combination against MTCRII and ACF in Balb/c mice, at 20 weeks after the start of treatment. MTCRII were unaffected by lambdaCgN alone. Combined lambdaCgN/MNU treatments induced greater MTCRII (P < 0.01) as well as greater number (P < 0.001) and crypt multiplicity (P < 0.01) of ACF than MNU alone. MTCRII were approximately 10-fold more numerous than ACF, although linear correlations were observed between these parameters (r = 0.732; P < 0.01). MTCRII are induced by lambdaCgN/MNU interactions in sufficient numbers to provide statistical power from relatively small sample sizes and correlate with ACF formation. MTCRII could thus provide the basis for a novel medium-term murine bioassay relevant to early-stage colorectal tumorigenesis.

Animals↗

Meta-analysis of sentinel node imprint cytology in breast cancer.

BACKGROUND: Intraoperative diagnosis of breast cancer metastases in axillary sentinel nodes is desirable to avoid a second operation for lymphadenectomy. Imprint or touch-preparation cytology is a popular technique that has high specificity and a wide range of sensitivity. METHODS: A systematic search of electronic databases was performed. Included articles were assessed for methodological and reporting quality. Random-effects model pooled estimates of sensitivity and specificity were calculated. Single-variable and multivariable meta-regression analyses were performed for predictors of sensitivity. RESULTS: Thirty-one studies were included; all were of good methodological quality but reporting quality varied. Pooled sensitivity of imprint cytology was 63 (95 per cent confidence interval (c.i.) 57 to 69) per cent and specificity was 99 (95 per cent c.i. 98 to 99) per cent. Pooled sensitivity for macrometastases was 81 per cent and that for micrometastases 22 per cent. Mean or median primary tumour size (P = 0.004), the prevalence of metastases (P = 0.103) and the proportion of micrometastases (P = 0.022) were significant risk factors in single-variable meta-regression analysis. Only the proportion of micrometastases remained significant in multivariable analysis. Frozen sectioning had better sensitivity than imprint cytology in three of four direct comparisons. CONCLUSION: Imprint cytology is simple and rapid, and has good sensitivity for macrometastases. The significance of poor sensitivity for micrometastases will be determined by trials investigating their natural history.

Breast↗

Computer-assisted instruction: guiding learning through a key features approach in a community-based medical course.

Computer assisted instruction (CAI) offers a valuable adjunct to the difficulties encountered in teaching medical students in a community-based course in rural Australia. The paper outlines the educational planning processes behind the project and provide an outline of the modular solution to the task. Preliminary results show that this approach is feasible and acceptable to guide students' learning.

Computer-Assisted Instruction↗

Teaching on the run: teaching skills for surgical trainees.

BACKGROUND: Increasing recognition of the need for training in teaching skills for clinical teachers has coincided with data that registrars and residents conduct much 'on the job' teaching as part of their routine work. While attention has been devoted to training consultants, support for the teaching role of the junior staff has been relatively neglected. The aim of the present report is to describe the teaching experiences of surgical registrars and the impact of a registrar teaching workshop. METHOD: A half-day programme combining presentation and discussion of surgical teaching with practical skills sessions was designed for surgical registrars at Prince of Wales Hospital. The programme included observation and feedback of brief teaching simulations at the bedside of volunteer patients to newly commenced clinical students, and small group sessions on clinic and operating theatre teaching. A pre-workshop questionnaire sought information about the registrars' own teaching, and a survey 3 months after the workshop determined if any changes to teaching practice had occurred. RESULTS: The registrars were generally moderately to very confident with their teaching ability but more than 75% felt that they were more confident after the workshop. Only three of 39 registrars had received any instruction aimed at improving their teaching skills, yet 34/39 had taught either on the ward, in the clinics or in the operating room. Follow-up after 3 months revealed that most registrars were enjoying their teaching tasks more, and half had increased their teaching since the workshop and began discussing teaching with their surgical colleagues. CONCLUSIONS: The present project demonstrates that relatively brief interventions focused on skill development may enhance the confidence and enjoyment of junior clinical teachers and increase the frequency of 'teaching on the run'.

Attitude of Health Personnel↗

Management of the axilla in early breast cancer: is it time to change tack?

The standard surgical treatment of the axilla in patients with early breast cancer is about to undergo a radical change. Although axillary dissection is an excellent procedure for both staging and local control, particularly in the clinically positive axilla, it has considerable morbidity and may understage a significant proportion of patients, because it will usually miss micrometastases that can occur in approximately 10% of 'node negative' patients. An increasing number of patients whose tumours are either non-invasive (ductal carcinoma in situ; DCIS), micro-invasive, tubular cancers or low-grade T1a tumours without lymphovascular invasion may be spared axillary surgery because the risk of axillary disease is 0-3%. Many studies, both prospective trials and large retrospective series, show that axillary radiotherapy alone provides similar local control rates to axillary dissection in patients with clinically negative axillas. Primary treatment of the axilla with radiotherapy alone, however, does not allow appropriate staging. Sentinel lymph node biopsy is being increasingly used in patients with breast cancer to provide this information. When a sentinel node is identified it is equal to or better than axillary dissection for staging the axilla and, if the node is positive, it will help select patients who should then proceed to further axillary surgery or axillary radiotherapy. Although sentinel lymph node biopsy is being rapidly adopted in many centres worldwide, the results of randomized controlled trials are needed before it can be recommended as the standard of care.

Axilla↗

Decreasing lengths of stay: the cost to the community.

BACKGROUND: Patients who are discharged earlier from hospital frequently require support from professional and unpaid carers at home after discharge. Hospitals save money per patient by discharging earlier, but it is not known whether the costs to community services and unpaid caters outweigh the savings to the hospital. METHODS: We prospectively studied the total costs, patient satisfaction, time off work and pain scores of 224 patients who underwent elective herniorrhaphy or laparoscopic cholecystectomy and who lived locally before and after re-engineering the elective surgical service. The components of the re-engineered surgical service were a peri-operative unit, pre-admission anaesthetic assessment based on self-reported questionnaires, day of surgery admissions, enhanced patient education, clinical pathways, and post-acute care. RESULTS: The patients treated through the re-engineered surgical service had a significantly shorter length of stay (LOS) (mean LOS: 2.2 vs 3.2 days; P < 0.001) but neither they nor their carers required more time off work. Significant determinants of time off work were smoking, heavy lifting at work and a higher pain score at day 7. Patients treated through the re-engineered surgical service recorded significantly higher satisfaction with their treatment. The cost saving to the hospital outweighed the cost of increased services provided in the community, so that the overall cost of providing treatment was over $200 less per patient through the re-engineered service. CONCLUSIONS: This study demonstrates that changes in care provision that result in shorter LOS and greater cost effectiveness may better meet patients' needs than existing systems.

Adult↗

Restricted TCR Valpha gene rearrangements in T cells recognizing an immunodominant peptide of myelin basic protein in DR2 patients with multiple sclerosis.

T cell responses to myelin basic protein (MBP) are thought to play an important role in the pathogenesis of multiple sclerosis (MS). The response to the 83-99 region of MBP represents a dominant response to MBP in patients with MS and is associated with HLA-DR2 that is linked with susceptibility to MS. Although T cell clones reactive to various regions of MBP have been found to exhibit heterogeneous TCR Vbeta gene usage in patients with MS, it is unclear whether T cell clones uniformly recognizing the 83-99 peptide of MBP in the context of the same DR molecule would have restricted TCR V gene rearrangements and recognition motifs. In this study, a panel of DR2- or DR4-restricted T cell clones specific for the MBP83-99 peptide were derived from 11 patients with MS and examined for TCR V gene usage by PCR and the recognition motifs using analog peptides. Our study revealed that despite a few T cell clone pairs having similar recognition motifs and shared sequence homology in the CDR3, the overall recognition motifs of MBP83-99-specific T cells were considerably diverse. Interestingly, the DR2-restricted T cell clones displayed a biased V gene usage for Valpha3 and Valpha8, while Vbeta gene rearrangements were highly heterogeneous. This study provided experimental evidence suggesting a limited heterogeneity in TCR Valpha gene rearrangements of MBP-reactive T cells in DR2 patients with MS.

Amino Acid Sequence↗

The incidence of sinusitis in patients with multiple sclerosis.

A retrospective study was performed to assess the incidence of sinus disease in patients with MS. The MRI scans of 108 patients referred to a regional Neurosciences Unit with a diagnosis of multiple sclerosis were examined. There were 71 females and 37 males with an age range of 22 to 67 years (mean: 39.7 years). The sagittal and axial images were reviewed and the degree of sinus disease noted. This was graded as absent, minimal, polypoid and pansinus. Fifty-seven patients (53%) had disease, the most common sinus involved was the maxillary followed by the ethmoid, frontal and sphenoid. Thirty-six patients had bilateral disease affecting the ethmoid sinuses most commonly. Three patients had fluid levels and four patients had retention cysts. The incidence of sinus disease is higher than in some other studies of normal populations.

Adult↗

Bartter's syndrome in two generations of an Irish family.

We report four cases of Bartter's syndrome in two consecutive generations of an Irish family. Diagnoses were made on the basis of characteristic clinical features, blood and urine biochemistry with additional evidence from renal biopsy in one case. The aetiology, treatment and inheritance of the syndrome are discussed.

Adult↗

Rectal epithelial gamma/delta T-lymphocyte responses to local gluten challenge in coeliac disease.

The proportion of intra-epithelial lymphocytes (IEL) that utilize the gamma/delta form of the T-cell receptor (TCR) is increased in coeliac disease, but their function remains unexplained. The response of intra-epithelial lymphocytes to rectal gluten challenge in coeliac and control subjects was studied after a rectal challenge of 2 g of Frazer's fraction III. A marked rise in CD3+ IEL occurred after challenge in the coeliac patients, peaking at 6 h and returning to normal by 48 h, with no significant changes in the gamma/delta TCR+ IEL. The IEL did not significantly change after gluten challenge in the controls. Acute gluten challenge induces infiltration of the rectal mucosa by T cells in coeliac patients, which is not accompanied acutely by increased numbers of gamma/delta TCR+ IEL. This study supports the hypothesis that alpha/beta TCR+ T cells may be of importance in the early response of coeliac patients to local gluten challenge.

Adult↗

Developmental disorders of the lymphatic system.

Approximately 67% of human conceptuses die prenatally. Of these, a significant number involve a disorder of the lymphatic system. A small number of live-born children also exhibit congenital lymphatic malformations, including an estimated 60% of patients with Turner syndrome. These observations have prompted a search for the genetic and dysmorphologic basis and the different patterns of congenital lymphedema and associated anomalies. In this article, we attempt to summarize available pertinent information on congenital disorders of the lymphatic system and to propose a conceptual overview of lymphatic development.

Adult↗

An unusual thyroid cyst. A case report.

A solitary hydatid cyst in a 69-year-old woman presented as a cold area on thyroid scan. Clinically, it forms part of the differential diagnosis of neoplastic thyroid lesions. Surgery is effective for this uncommon thyroid cyst.

Aged↗

Location of osteoclast precursors in fetal rat calvaria cultured on collagen gels.

Although osteoclasts are derived from hematopoietic cells, the exact identity of their precursors and the mechanism for their recruitment onto bone surfaces remain unclear. We wished to study their differentiation in the fetal rat calvaria and to locate its source of osteoclast precursor cells. Osteoclasts were detected by neutral red staining or cytochemical reaction for acid phosphatase of intact bone (cell number and area measured by computerized image analysis) or in cryostat sections of bone (enzyme activity measured by quantitative cytochemistry). Histology of semithin sections of fixed bones was also examined. The 19 day calvariae contained few mature osteoclasts. After 48 h culture on gels of type 1 collagen (1.5 mg/ml) supplemented with 5 mM calcium beta-glycerophosphate, 10 mM proline, and 2 micrograms/ml ascorbic acid, numerous large osteoclasts were seen on their endocranial surfaces. In contrast, cell morphology and enzyme activity deteriorated in bones cultured in liquid medium. The cells that formed in vitro rapidly responded to calcitonin by contraction. Stripping of endocranial membranes from the calvariae prevented osteoclast formation in culture, but these cells were seen when "stripped" bones had been cocultured with their membranes for 48 h or with intact 16 day calvariae (well before the onset of osteogenesis). Few osteoclasts were found when an 0.22 micron filter was inserted between the stripped calvaria and the endocranial membranes. We conclude that the endocranial membranes, which contain the meningeal blood vessels, are a major source of osteoclast precursors and that these cells are present in calvarial tissue even before the onset of osteogenesis.

Acid Phosphatase↗

Cellular basis for defective electrolyte transport in inflamed human colon.

Electrolyte transport pathways in distal colonic mucosa from patients with noninflammatory and inflammatory (ulcerative colitis, Crohn's colitis) disease of the large bowel were studied in vitro with electrophysiological techniques. Noninflamed tissues exhibited substantial amiloride-sensitive electrogenic sodium transport. In contrast, inflamed but structurally intact tissues exhibited only a modest degree of electrogenic sodium transport, significant increases in total tissue conductance and apical membrane conductance, and a 100% increase in the arachidonic acid content of the cell membrane fraction of mucosal homogenates. Replacement of chloride with gluconate decreased total tissue conductance to a greater extent in inflamed than in noninflamed tissues, and total tissue conductance was higher in inflamed than in noninflamed tissues in the presence of transepithelial potassium and sodium gradients, suggesting enhanced mucosal "leakiness" to anions and cations in acute colitis. Apical addition of nystatin virtually abolished amiloride-sensitive apical sodium uptake in both groups, indicating that the ionophore formed channels in the apical membrane of noninflamed and diseased mucosa. Additional studies showed that mucosal inflammation decreased maximal activity of the basolateral sodium pump by 76%. Thus, defects in the biophysical properties of colonic epithelial cell membranes are likely to be important factors in the pathogenesis of diarrhea in ulcerative and Crohn's colitis.

Adult↗