Late cardiac effects of chemotherapy in breast cancer survivors treated with adjuvant doxorubicin: 10-year follow-up.

Doxorubicin (Dox), a mainstay of adjuvant breast cancer treatment, is associated with cardiac toxicity in the form of left ventricular dysfunction (LVD), LV diastolic dysfunction, or LV systolic dysfunction. Study objectives were to evaluate the prevalence of LVD in long-term breast cancer survivors treated with Dox and determine if brain-type natriuretic peptide (BNP) may help identify patients at risk for LVD. Patients who participated in prospective clinical trials of adjuvant Dox-based chemotherapy for breast cancer with a baseline left ventricular (LV) ejection fraction evaluation from 1999 to 2006 were retrospectively identified from the St Vincent's University Hospital database. Patients were invited to undergo transthoracic echocardiography, BNP analysis, and cardiovascular (CV) risk factor assessment. LVDD was defined as left atrial volume index >34 mL/m(2) and/or lateral wall E prime <10 m/s, and LVSD as LVEF <50 %. Of 212 patients identified, 154 participated, 19 patients had died (no cardiac deaths), and 39 declined. Mean age was 60.7 [55:67] years. A majority of the patients (128, 83 %) had low CV risk (0/1 risk factors), 21 (13.6 %) had 2 RFs, and 5 (3.2 %) ≥3 RFs. BMI was 27.2 ± 4.9 kg/m(2). Median Dox dose was 240 mg/m(2) [225-298]; 92 patients (59.7 %) received ≤240 mg/m(2) and 62 (40.3 %) > 240 mg/m(2). Baseline LVEF was 68.2 ± 8 %. At follow-up of 10.8 ± 2.2 years, LVEF was 64.4 ± 6 %. Three (1.9 %) subjects had LVEF <50 % and one (0.7 %) had LVDD. Dox >240 mg/m2 was associated with any LVEF drop. BNP levels at follow-up were 20.3 pg/ml [9.9-36.5] and 21.1 pg/ml [9.8-37.7] in those without LVD and 61.5 pg/ml [50-68.4] in those with LVD (p = 0.04). Long-term prospective data describing the impact of Dox on cardiotoxicity are sparse. At over 10 years of follow-up, decreases in LVEF are common, and dose related, but LVD as defined is infrequent (2.6 %). Monitoring with BNP for subclinical LVD needs further evaluation.

Importance of risk factor management in diabetic patients and reduction in Stage B heart failure.

BACKGROUND: A number of studies have demonstrated the presence of a diabetic cardiomyopathy, increasing the risk of heart failure development in this population. Improvements in present-day risk factor control may have modified the risk of diabetes-associated cardiomyopathy. AIM: We sought to determine the contemporary impact of diabetes mellitus (DM) on the prevalence of cardiomyopathy in at-risk patients with and without adjustment for risk factor control. DESIGN: A cross-sectional study in a population at risk for heart failure. METHODS: Those with diabetes were compared to those with other cardiovascular risk factors, unmatched, matched for age and gender and then matched for age, gender, body mass index, systolic blood pressure and low density lipoprotein cholesterol. RESULTS: In total, 1399 patients enrolled in the St Vincent's Screening to Prevent Heart Failure (STOP-HF) cohort were included. About 543 participants had an established history of DM. In the whole sample, Stage B heart failure (asymptomatic cardiomyopathy) was not found more frequently among the diabetic cohort compared to those without diabetes [113 (20.8%) vs. 154 (18.0%), P = 0.22], even when matched for age and gender. When controlling for these risk factors and risk factor control Stage B was found to be more prevalent in those with diabetes [88 (22.2%)] compared to those without diabetes [65 (16.4%), P = 0.048]. CONCLUSION: In this cohort of patients with established risk factors for Stage B heart failure superior risk factor management among the diabetic population appears to dilute the independent diabetic insult to left ventricular structure and function, underlining the importance and benefit of effective risk factor control in this population on cardiovascular outcomes.

Improving consultations in oncology: the development of a novel consultation aid.

BACKGROUND: The way in which patients receive bad news in a consultation can have a profound effect in terms of anxiety, depression and subsequent adjustment. Despite investment in well-researched communication skills training and availability of decision-making aids, communication problems in oncology continue to be encountered. METHODS: We conducted a mixed-methods study in a large UK Cancer Centre to develop a novel consultation aid that could be used jointly by patients and doctors. Consultations were audio-recorded and both the doctors and the patients were interviewed. We used conversation analysis to analyse the consultation encounter and interpretative phenomenological analysis to analyse the interviews. Key themes were generated to inform the design of the aid. RESULTS: A total of 16 doctors were recruited into the study along with 77 patients. Detailed analysis from 36 consultations identified key themes (including preparation, information exchange, question-asking and decision making), which were subsequently addressed in the design of the paper-based aid. CONCLUSIONS: Using detailed analysis and observation of oncology consultations, we have designed a novel consultation aid that can be used jointly by doctors and patients. It is not tumour-site specific and can potentially be utilised by new and follow-up consultations.

Patient-initiated questions: How can doctors encourage them and improve the consultation process? A qualitative study.

OBJECTIVE: To investigate the circumstances under which patients initiate direct questions in oncology consultations. DESIGN: Conversation analysis of 47 consultations between oncologists and patients with cancer. SETTING: An oncology clinic at a teaching hospital in the East Midlands. PARTICIPANTS: 16 Oncologists and 67 cancer patients. OUTCOME MEASURE: Patient initiated direct questions. RESULTS: On the whole patients' direct questions are designed to seek specific information regarding, the cancer itself, treatment options or their experience of symptoms. When patients do ask direct questions they typically follow the announcement of test results where some reference to the details of those results, is provided. More specifically, there seems to be a relation between showing the patient their scan/X-ray results, patient involvement and patient-initiated direct questions. Higher levels of patient-initiated direct questions were clustered around occasions where doctors provided information and explanations of test results (12 consultations) sometimes with direct reference to scan or X-ray results (7 consultations). CONCLUSIONS: This study highlights the importance of careful explanation of diagnostic evidence as a factor contributing to increased patient involvement. More specifically, the findings suggest that, when appropriate, invoking diagnostic evidence (eg, scan or X-ray results) is an effective way of increasing levels of patient question asking. Doctors need to be able to encourage patient question asking to ensure that patients have at their disposal an important means through which they can determine their information needs. Although these results come from a study of oncology consultations, the findings may be transferable to other clinical contexts.

Communication challenges in surgical oncology.

In this essay we set out clinical communication challenges in surgical oncology. We draw directly on relevant examples where they are available. Otherwise, we refer to the more generic surgical and medical literature. We offer 'macro' and 'micro' perspectives on clinical communication. That is, exploring communication challenges at the level of the organization and between individuals, doctors and patients and interprofessionally across different settings. Training content and methods are reported that address the complex communication challenges associated with surgical oncology. Innovations in simulation-based education offer exciting new opportunities for formative and summative assessment. We outline limitations of the essay and finally propose the content of a surgical oncology communication program.

Dyslipidemia therapy update: the importance of full lipid profile assessment.

Lipid guidelines typically focus on total cholesterol +/- low-density lipoprotein cholesterol levels with less emphasis on high-density lipoprotein cholesterol (HDL-C) or triglyceride assessment, thus potentially underestimating cardiovascular (CV) risk and the need for lifestyle or treatment optimization. In this article, we highlight how reliance on isolated total cholesterol assessment may miss prognostically relevant lipid abnormalities; we describe from the European Systematic COronary Risk Evaluation (SCORE) data set how incorporation of HDL-C may improve estimation of CV risk; and, finally, we critically evaluate the evidence base surrounding triglycerides and CV risk.

Ethical reflection on the harm in reproductive decision-making.

Advances in reproductive technologies continue to present ethical problems concerning their implementation and use. These advances have preoccupied bioethicists in their bid to gauge our moral responsibilities and obligations when making reproductive decisions. The aim of this discussion is to highlight the importance of a sensibility to differences in moral perspective as part of our ethical inquiry in these matters. Its focal point is the work of John Harris(i), who has consistently addressed the ethical issues raised by advancing reproductive technologies. The discussion is aimed at a central tenet of Harris's position on reproductive decision-making-namely, that in some instances, giving birth to a worthwhile life may cause harm and will therefore be morally wrong. It attempts to spell out some of the implications of Harris's position that the author takes to involve a misplaced generality. To support this claim, some examples are explored that demonstrate the variety of ways in which concepts (such as harm) may manifest themselves as moral considerations within the context of reproductive decision-making. The purpose is to demonstrate that Harris's general conception of the moral limits of reproductive autonomy obscures the issues raised by particular cases, which in themselves may reveal important directions for our ethical inquiry.

Single coronary artery: a familial clustering.

A 59 year old man undergoing investigation for chest pain was found at elective coronary angiography to have a single coronary artery; the left coronary had a normal distribution, with the right coronary originating as a continuation of the atrioventricular circumflex. His 30 year old daughter was admitted for elective coronary angiography for further investigation of a dilated cardiomyopathy. She was also found to have a single coronary artery. However, in her case, the right and left coronary arteries arose from the right sinus of Valsalva; the right coronary had a normal distribution, the left coronary passed anterior to the pulmonary trunk and aorta.

In vitro stability and immunoreactivity of the native and recombinant plant food 2S albumins Ber e 1 and SFA-8.

BACKGROUND: The ability of an intact protein to reach the circulatory system may be a prerequisite to allergenicity and many allergens, particularly those from plant foods, have been found to be consistently more resistant to digestion by pepsin than other proteins. OBJECTIVE: This study assessed the pepsinolytic stability of native 2S albumins from Brazil nut and sunflower seed and their recombinant versions produced in Pichia pastoris. The physicochemical stability of native and recombinant Brazil nut 2S albumins and recombinant sunflower seed 2S albumin was also assessed. The immunoreactivity of native Brazil nut 2S albumin and recombinant 2S albumins was compared using serum from patients allergic to Brazil nuts and animals immunized with native 2S albumins. METHODS: Digestibility was measured in simulated gastric fluid followed by SDS-PAGE. Circular dichroism spectra were used to analyse unfolding, as proteins were denatured by temperature, pH and guanidinium chloride. Immunoreactivity was assessed by immunoblot, RAST and ELISA. RESULTS: Brazil nut 2S albumin was significantly more resistant to proteolytic digestion than other Brazil nut proteins. It was also resistant to thermally and chemically induced denaturation. Equally high resistance to proteolytic digestion was observed with sunflower seed 2S albumin. The recombinant albumins mirrored their native counterparts in stability and immunoreactivity. CONCLUSION: The important food allergen Brazil nut 2S albumin is as stable to digestion as is sunflower seed 2S albumin, whose allergenicity has yet to be determined. The 2S albumins and their recombinant counterparts could not be easily denatured by physicochemical treatments. The results suggest that 2S albumin is the only Brazil nut protein to reach the gut immune system intact. The production of properly folded recombinant proteins will facilitate mechanistic studies as well as diagnostic testing and antigen-based therapies.

Stability of recombinant 2 S albumin allergens in vitro.

Two well known 2 S albumins, Ber e 1 from brazil nut and sunflower 2 S albumin 8 (SFA-8), have been expressed in a eukaryotic system and purified. Analysis of recombinant versions of Ber e 1 and SFA-8 revealed them to be significantly more resistant to digestion by pepsin than BSA, and to be stable for up to 30 min in simulated gastric fluid. Unfolding monitored by CD indicated that both proteins were also very resistant to denaturation induced by heat and low pH. These results suggest that, although the ability of 2 S albumins to reach the circulatory system may be a prerequisite for the allergenicity of this group of proteins, stability is just one of a number of characteristics that provoke a selective immune response.

Absence of rapid terpene turnover in several diverse species of terpene-accumulating plants.

Terpenes are commonly believed to undergo rapid metabolic turnover in plants, but the evidence for this process comes largely from studies that used detached organs or applied radiolabeled precursors in unnatural ways. When 14CO2 pulse labeling experiments were carried out with intact plants of four taxonomically distant, terpene-accumulating species, no significant turnover of monoterpenes, sesquiterpenes or diterpenes was detected in young foliage over a two week period after exposure to 14CO2. These results are consistent with those of other investigations performed under physiologically realistic conditions, and caution against the uncritical incorporation of turnover into models or theories concerning plant chemical defense.

Relation between plasma lignocaine levels and induced haemodynamic changes.

Intravenous lignocaine (1 mg./kg. body weight) was found to produce insignificant haemodynamic changes, and in particular no reduction in myocardial contractility. A rate of 2 mg./minute infused intravenously is suggested for therapeutic purposes.In anaesthetized dogs an infusion of 13.5 mg./minute caused moderate haemodynamic depression and a maximum plasma level of 7 mug./ml. Massive injections of 200 and 400 mg. of lignocaine produced a maximum plasma level of 13.8 and 27.8 mug./ml., respectively, and in the latter failure of myocardial contraction in the presence of a normal E.C.G. ensued ("pump failure"). Lignocaine appears to alter the uptake of calcium by myocardial sarcoplasmic reticulum, and this may explain the negative inotropic effect of large doses.