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Biomedical subjects

L Barr

Publications and source records attributed to L Barr.

At least 19 recordsLinked to original sources
PubMed2005

Surgical decisions made by 158 women with hereditary breast cancer aged <50 years.

AIM: To establish the uptake of contralateral risk reducing mastectomy in women informed of their risks and options at time of diagnosis of their primary unilateral breast cancer. METHODS: We have assessed the surgical choices of 70 women diagnosed with breast cancer <50 years as part of a family history surveillance program and fully informed about their contralateral risks and surgical options. We have compared this to women from other surgical clinics who were subsequently found to harbour a pathogenic BRCA1/2 mutation. RESULTS: Sixty-five percent (13/20) of BRCA1/2 mutation carriers and 59% (n=20/34) of those at the highest level of risk pre-diagnosis (33+% lifetime risk) opted for contra-lateral mastectomy in the study sample. In contrast only 10% (n=9/88) women identified as mutation carriers from other clinics opted for such surgery. CONCLUSIONS: We would suggest that women with a significant family history and therefore a high contra-lateral breast cancer risk, should have these risks and management options discussed at the time of diagnosis of breast cancer.

Adult↗
PubMed2004

High-grade carcinomas of the breast showing patterns of mixed ductal and myoepithelial differentiation (including myoepithelial cell-rich carcinoma of the breast).

AIMS: To assess the clinical, morphological and immunophenotypic characteristics of breast carcinomas showing patterns of mixed epithelial and myoepithelial differentiation. METHODS AND RESULTS: Included in the study were four carcinomas containing a mixed population of epithelial and myoepithelial cells identified using morphological features at the light microscopic level which were found amongst a review of 500 archival cases and two recently accessioned cases. The carcinomas varied in size from 20 to 38 mm and all were grade 3 ductal carcinomas. Most showed nodular and sheet-like cellular aggregates, although one case showed small solid cell aggregates with duct formation. The cells were large, round, polygonal or spindle-shaped and had areas of clear or eosinophilic cytoplasm in variable proportions. Foci of metaplasic carcinoma were present in three cases. All cases showed strong, patchy positivity for cytokeratin (CK)14, calponin, smooth actin and muscle specific actin. Epithelial membrane antigen and CK8 were positive in a similar proportion of cells. One patient died 23 months following diagnosis with metastatic carcinoma, another patient died of unrelated disease and four patients are alive with follow-up ranging from 18 months to 25 years. CONCLUSIONS: High-grade carcinomas of the breast showing patterns of mixed ductal and myoepithelial differentiation may show additional morphological features such as foci of metaplasia and appear to have a good prognosis similar to myoepithelial cell-rich carcinomas. However, young age and lymph node metastasis may portend a worse prognosis.

Adult↗
PubMed2003

Management of accessory breast tissue in the axilla.

BACKGROUND: Accessory breasts occur in 0.4-6 per cent of women. They may be asymptomatic or cause pain, restriction of arm movement, cosmetic problems or anxiety. It is currently recommended that all accessory breasts be removed surgically but complications following this procedure have been poorly documented. METHODS: All patients who presented with axillary accessory breasts between July 1999 and October 2000 were identified from a computer database. A retrospective review of patients listed for excision of accessory breast tissue was undertaken to determine any postoperative complications. RESULTS: Women with axillary accessory breasts represented 0.5 per cent of all new referrals. A total of 28 women (80 per cent of those diagnosed) had surgery. Eleven patients experienced postoperative complications; the majority followed operations performed by a trainee. CONCLUSION: Excision of accessory axillary breast tissue was associated with significant morbidity.

Axilla↗
PubMed2003

Long term results of a randomised prospective study of preservation of the intercostobrachial nerve.

AIM: We have previously reported in a randomised controlled trial comparing intercostobrachial nerve (ICBN) preservation with division that no difference in symptoms was seen between the groups at 3 months follow-up although a reduced area of sensory loss was measured on the arm. To determine if longer follow-up provides evidence for ICBN preservation, follow-up of patients in the trial at 3 years (range 32-38 months) postoperatively was performed. METHODS: Sensory symptoms and deficits, pain, shoulder movements, arm circumference and the presence of neuromas were documented in 73 patients from the original group of 120. RESULTS: No difference in survival or axillary recurrence was observed. The only symptom which differed between the two groups was a subjective assessment of 'different sensation' (P=0.006). No significant difference was observed in other sensory symptoms, pain, shoulder movement, arm circumference or presence of neuromas. A larger area of sensory deficit was measured in women with sacrificed nerves compared to preserved (P=0.009). CONCLUSION: Preservation of the intercostobrachial nerve does not affect patient survival. It improves patient sensory deficit significantly and modestly improves long-term symptoms.

Adult↗
PubMed2001

Extent of excision margin width required in breast conserving surgery for ductal carcinoma in situ.

BACKGROUND: Breast conserving surgery (BCS) is common practice for unifocal ductal carcinoma in situ (DCIS) less than 4 cm in size, but the extent of tumor free margin width around DCIS necessary to minimize recurrence is unclear. METHODS: Clinical and pathologic details were recorded from all patients with pure DCIS < 4 cm in size, treated with BCS between 1978 and 1997. Histologic margins were measured by using an ocular micrometer. Patients with clear margins (> 1 mm) were divided up into 3 groups for analysis based on margin of normal tissue excised: 1.1-5 mm, 5.1-10 mm, and 10.1-40 mm. RESULTS: There were 66 patients with close margins (< or = 1 mm), of which 25 cases (37.9%) recurred. The recurrence rates for the 3 clear margin groups ranged from 4.5-7.1%. Median followup was 47 months (range 12-197 mos). Risk of recurrence in the group with close margins was greater than the subgroups with clear margins (P < 0.001); no differences in recurrence was seen between the individual subgroups with clear margins. Nuclear Grade 3 was predictive of recurrence (P = 0.03). Following excision alone, the recurrence rate was 18.6%, compared with 11.1% when radiotherapy was given as adjuvant therapy. Women with clear margins following excision had a recurrence rate of only 8.1%. CONCLUSION: After BCS for DCIS, close margins were associated with a high risk of local recurrence. Radiotherapy did not compensate for inadequate surgical clearance.

Adult↗
PubMed2001

There may never be a final cure for breast cancer.

This paper challenges the perception that the success of the human genome project has brought us to the threshold of a cure for many common cancers. Paradoxically, the message emerging from the genetics of breast cancer may be that the genetic damage associated with malignant transformation, and the mutations predisposing to the disease in our gene pool, may prove impossible to eliminate.

Breast Neoplasms↗
PubMed2001

Mixed apocrine/endocrine ductal carcinoma in situ of the breast coexistent with lobular carcinoma in situ.

An unusual mixed form of ductal carcinoma in situ (DCIS) of the breast is described, which exhibits a biphenotypic morphology encompassing a range of differential diagnostic DCIS subtypes. In addition, immunophenotypic and ultrastructural studies demonstrate neuroendocrine and apocrine differentiation, raising questions regarding appropriate classification and biological behaviour. In two cases, coexistence of this mixed form of DCIS with lobular carcinoma in situ (LCIS) in the same duct lobular units is an additional unusual feature that might, at least in some cases, indicate a closer relation between them.

Apocrine Glands↗
PubMed2001

Enoxaparin and abciximab adjunctive pharmacotherapy during percutaneous coronary intervention.

Randomized controlled trials of patients with non-ST segment elevation acute coronary syndromes have established the superiority of enoxaparin (versus unfractionated heparin) for reducing adverse ischemic outcomes. Furthermore, adjunctive abciximab therapy during percutaneous coronary intervention (PCI) is associated with improved clinical outcomes. Since algorithms for integrating these pharmacotherapies have not been determined, patients undergoing elective PCI were enrolled into 2 distinct and separate studies conducted by the National Investigators Collaborating on Enoxaparin (NICE) study groups (NICE 1 and NICE 4 studies). Patients in NICE 1 were administered enoxaparin 1.0 mg/kg intravenously (without abciximab) and those enrolled in NICE 4 were administered a reduced dose (0.75 mg/kg) of enoxaparin in combination with standard-dose abciximab intravenously during PCI. Bleeding events and ischemic outcomes assessed in-hospital and at 30-days post-PCI were infrequent with either pharmacologic regimen. In the dose regimens studied, enoxaparin with or without abciximab appears to provide safe and effective anticoagulation during PCI. The combination of reduced-dose enoxaparin and abciximab was associated with a low incidence of adverse outcomes (bleeding or ischemic events). Additional studies may be required to establish the relative safety and efficacy of this new adjunctive pharmacologic strategy when compared with the combination of low-dose, weight-adjusted unfractionated heparin and abciximab.

Abciximab↗
PubMed2000

Force relaxes before the fall of cytosolic calcium in the photomechanical response of rat sphincter pupillae.

In the rat sphincter pupillae, as in other smooth muscles, the primary signal transduction cascade for agonist activation is receptor --> G protein --> phospholipase C --> inositol trisphosphate --> intracellular Ca(2+) concentration ([Ca(2+)](i)) --> calmodulin --> myosin light chain kinase --> phosphorylated myosin --> force development. Light stimulation of isolated sphincters pupillae can be very precisely controlled, and precise reproducible photomechanical responses (PMRs) result. This precision makes the PMR ideal for testing models of regulation of smooth muscle myosin phosphorylation. We measured force and [Ca(2+)](i) concurrently in sphincter pupillae following stimulation by light flashes of varying duration and intensity. We sampled at unusually short (0.01-0.02 s) intervals to adequately test a PMR model based on the myosin phosphorylation cascade. We found, surprisingly, contrary to the behavior of intestinal muscle and predictions of the phosphorylation model, that during PMRs force begins to decay while [Ca(2+)](i) is still rising. We conclude that control of contraction in the sphincter pupillae probably involves an inhibitory process as well as activation by [Ca(2+)](i).

Animals↗
PubMed2000

Combination enoxaparin and abciximab therapy during percutaneous coronary intervention: "NICE guys finish first".

Data from randomized clinical trials support the administration of both enoxaparin and platelet glycoprotein IIb/IIIa blockade to patients who present with non-ST segment evaluation acute coronary syndromes. Enoxaparin does not activate platelets, has a more predictable dose response that facilitates weight-adjusted dosing and may have enhanced antithrombotic (increased anti-Xa activity) and safety (reduced anti-IIa activity) properties when compared with unfractionated heparin. Abciximab administration during percutaneous coronary intervention reduces the incidence of ischemic adverse outcomes and may improve survival in long-term follow-up. The preliminary experience with combining abciximab and intravenous enoxaparin during percutaneous coronary intervention in the NICE-4 Trial demonstrates a low incidence of minor/major bleeding (TIMI definition) and transfusion and infrequent major cardiac events to 30 days follow-up. Future algorithms to facilitate the transition of patients from the clinical service who have received subcutaneous administration of enoxaparin to the cardiac catheterization laboratory prior to percutaneous coronary intervention are forthcoming and will provide seamless integration of "optimal" adjunctive pharmacology through the course of hospitalization for patients with non-ST elevation acute coronary syndromes.

Abciximab↗
PubMed2000

Combination Enoxaparin and Abciximab During Percutaneous Coronary Intervention: A New Standard of Care?

Evidence from randomized trials supports the administration of platelet glycoprotein (GP) IIb/IIIa blockade both to patients undergoing percutaneous coronary intervention (PCI) and those presenting with non-ST elevation acute coronary syndromes (ACSs). Similarly, the low molecular weight heparin (LMWH), enoxaparin, has demonstrated superior efficacy when compared with unfractionated heparin (UFH) in the treatment of patients with non-ST elevation ACS. Algorithms for seamless integration of pharmacotherpy through the course of hospitalization for patients who present with ACS and who require PCI will likely combine therapy with enoxaparin and platelet GP IIb/IIIa blockade (abciximab). Our preliminary experience with combination enoxaparin and abciximab as adjunctive pharmacotherapy for PCI suggests that this strategy is safe and effective and may offer advantages over a conventional strategy, which employs UFH.

Journal Article↗
PubMed1999

New ultraviolet signal actuated switching valve for the measurement of low level impurities by liquid chromatography/mass spectrometry.

A new ultraviolet (UV) signal actuated switching valve for diverting the main matrix compound to waste, preventing it entering the ion source of the mass spectrometer is described. Sensitivity for trace impurities eluting after the drug substance cimetidine or related compounds could be enhanced by a factor of 4-5. The increase in sensitivity was dependent on the type of ion source which interfaced the mass spectrometer. The benefit of the switching valve was greater with a line of sight type source than with an orthogonal one. The detection limit for a trace compound in a matrix compound was improved by up to a factor of 10 with the line of sight type source but only by a factor of 5 with the orthogonal source.

Cimetidine↗
PubMed1999

Effect of glycoprotein IIb/IIIa inhibition without thrombolytic therapy on reperfusion in acute myocardial infarction: results of ReoMI pilot study.

The efficacy of abciximab and moderate dose heparin in attaining reperfusion in acute MI was tested in a multicenter pilot study. Patients with acute MI of less than 6-hr onset triaged to primary PTCA received intravenous abciximab bolus and infusion and heparin (70 u/kg) in the emergency room. Mean time to angiography from administration of abciximab was 34 +/- 23 min. TIMI flow rates were: grade 0-62%, grade I-20%, grade II-9%, and grade III-9%. Primary PTCA was performed with 100% success rate. Access site bleeding occurred in 10% of patients with no incidence of intracranial bleeding. TIMI II/III flow rates were 50% in a patient subset where angiography was delayed by 45 min. While not an alternative to thrombolytics in AMI, abciximab administration in the emergency room in patients triaged to PTCA may be beneficial in situation where door to needle time is delayed as TIMI II/III flows may be attained in some patients. Cathet. Cardiovasc. Intervent. 48:430-434, 1999.

Abciximab↗
PubMed1999

Further evidence for the selective disruption of intercellular communication by heptanol.

The lack of selective gap junctional uncoupling agents has hampered evaluation of the contribution of intercellular communication to pharmacomechanical coupling and vascular contractility. Thus we further explored the utility and selectivity of heptanol as a gap junctional uncoupling agent in isolated rat aortic rings. Fifty-two aortic rings were obtained from 15 rats and were precontracted to approximately 75% of maximum with phenylephrine (PE). When contraction achieved steady state (approximately 5 min), a single concentration of heptanol (200 microM) was added to each aortic ring at 1- to 3-min intervals for up to 42 min post-PE addition. At early time points (5-10 min after PE), heptanol elicited an approximately 50% loss of tension (i.e., relaxation). At subsequent time points post-PE, a gradual and time-dependent decrease in the magnitude of the heptanol-induced relaxation was observed until, after approximately 40 min, addition of heptanol was associated with little, if any, detectable relaxation. Linear regression analysis of the magnitude of the heptanol-induced relaxation vs. the square root of the elapsed time interval (from addition of PE) revealed a highly significant negative correlation (P < 0.001, R = 0.81). Studies conducted on KCl-precontracted aortic rings revealed no detectable heptanol-induced relaxation after development of the steady-state KCl-induced contraction. These data extend our previous observations to further document the potential utility of heptanol as a "relatively selective" uncoupling agent.

Animals↗
PubMed1998

Randomised controlled trial of effects of early discharge after surgery for breast cancer.

OBJECTIVE: To determine the effect of early discharge from hospital after surgery for breast cancer on physical and psychological illness. DESIGN: Randomised controlled trial comparing discharge two days after surgery (before removal of drain) with standard management (discharge after removal of drain). SETTING: Regional breast unit. SUBJECTS: 100 women with early breast cancer undergoing mastectomy and axillary node clearance (20) or breast conservation surgery (80). MAIN OUTCOME MEASURES: Physical illness (infection, seroma formation, shoulder movement) and psychological illness (checklist of concerns, Rotterdam symptom questionnaire, hospital anxiety and depression scale) preoperatively and at one month and three months postoperatively. RESULTS: Women discharged early had greater shoulder movement (odds ratio 0.28 (95% confidence interval 0.08 to 0.95); P = 0.042) and less wound pain (odds ratio 0.28 (0.10 to 0.79); P = 0.016) three months after surgery compared with women given standard management. One month after surgery scores were significantly lower on the Rotterdam symptom questionnaire in patients who were discharged early (ratio of geometric mean scores 0.73 (0.55 to 0.98) P = 0.035), but rates of psychological illness generally did not differ between groups. CONCLUSIONS: Increased rates of physical or psychological illness did not result from early discharge after surgery for breast cancer. This policy can be recommended for patients with support at home.

Adult↗
PubMed1998

Multimodality treatment in the control of deep musculoaponeurotic fibromatosis.

BACKGROUND: Deep musculoaponeurotic fibromatoses are rare soft tissue neoplasms with a propensity for local recurrence. METHODS: A retrospective analysis was carried out of the factors contributing to local disease control in 75 patients treated between 1963 and 1993. RESULTS: Multivariate analysis identified the type of surgical excision (P < 0.001) and involvement of pathological resection margins (P < 0.02) as significant factors contributing to local recurrence. After a median follow up of 47 months (range 24 months to 29 years) 31 (49 per cent) of the 63 patients who had an 'adequate' surgical resection developed local recurrence. The median time before development of local recurrence was 83.4 (range 8-129) months in patients with clear pathological resection margins. This was significantly shortened to 13.1 (range 2-35) months in those with positive margins (P < 0.001). CONCLUSION: Adequate surgical extirpation is the most important determinant in local disease control. Treatment of local recurrence ranged from observation during periods of disease stabilization to multimodality treatment for aggressive disease.

Adult↗
PubMed1998

Prospective randomized controlled trial of preservation of the intercostobrachial nerve during axillary node clearance for breast cancer.

BACKGROUND: Complications of axillary surgery occur due to severance of the intercostobrachial nerve (ICBN). The feasibility and benefit of preserving the ICBN to prevent sensory loss was studied prospectively. METHODS: Sensory symptoms and deficits were documented, and shoulder movement and arm circumference were measured at discharge and 3 months later in 120 patients randomized to either preservation or division of the ICBN. RESULT: Preserving the ICBN was feasible in 39 (65 per cent) of the 60 patients randomized to the preservation group. Preserving the nerve prolonged the procedure by a median of 5 min. No difference in sensory symptoms between the groups was seen at 3 months. At 3 months 53 per cent of patients randomized to ICBN preservation had a sensory deficit compared with 84 per cent of those randomized to ICBN sacrifice (P < or = 0.05). CONCLUSION: Preserving the ICBN reduces the incidence of sensory deficit (but not symptoms) in patients after axillary clearance.

Adult↗