Isolated right ventricular infarct demonstrated by cardiac MRI.
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Diagnosis, Differential↗
Biomedical subjects
J Younger
Publications and source records attributed to J Younger.
The perioperative specialist practitioner: developing and evaluating a new surgical role.
INTRODUCTION: This paper describes the design, implementation and evaluation of a new professional role in surgery. The role of the perioperative specialist practitioner (PSP), conceived as a response to the Working Time Directive, provides integrated preoperative and postoperative care to patients undergoing surgery in hospital. METHODS: A 1-year training programme was designed, dealing with a wide range of knowledge, skills and attitudes. Effective communication was a key component. Nine intensive 5-day modules at Imperial College London (London, UK) alternated with supervised experience of the surgical team at each participant's home trust. Detailed evaluation of the role and the training programme was provided by an independent research team, using an interview-based qualitative approach. Observational data were provided by the project team. Data were analysed using standard qualitative methods. RESULTS: 27 PSPs across 12 National Health Service trusts took part in two PSP training programmes. A total of 124 interviews (94 individual and 30 group) were carried out with PSPs and their colleagues. Overall, the role was seen as successful and positive, with great potential for dealing with reductions in junior medical cover. Each site encountered different opportunities and problems. Lack of mentorship was a key issue, and the role provoked considerable opposition in trusts. The training programme was viewed as highly successful. DISCUSSION: PSPs can provide high levels of expertise, but within clear limits. Our training programme has been effective and is perceived to be of high quality. However, introducing a new role requires time and sensitivity if opposition is to be minimised.
Adult↗
Helicobacter pylori infection in elderly patients.
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Adult↗
Risk of pneumonitis in breast cancer patients treated with radiation therapy and combination chemotherapy with paclitaxel.
BACKGROUND: Some chemotherapy (CT) drugs, including taxanes, may enhance the effectiveness of radiation therapy (RT). However, combining these therapies may increase the incidence of radiation pneumonitis, a lung inflammation. In a retrospective cohort study, we evaluated the incidence of radiation pneumonitis in breast cancer patients treated with RT and standard adjuvant CT by use of doxorubicin (Adriamycin) and cyclophosphamide, with and without paclitaxel. METHODS: Forty-one patients with breast cancer were treated with RT and adjuvant CT, including paclitaxel. Paclitaxel and RT (to breast-chest wall in all and lymph nodes in some) were delivered sequentially in 20 patients and concurrently in 21 patients. Paclitaxel was given weekly in some patients and every 3 weeks in other patients. The incidence of radiation pneumonitis was compared with that among patients in our database whose treatments did not include paclitaxel (n = 1286). The percentage of the lung volume irradiated was estimated. The Cox proportional hazards model was used to find covariates that may be associated with the observed outcomes. All P values were two-sided. RESULTS: Radiation pneumonitis developed in six of the 41 patients. Three patients received paclitaxel concurrently with RT, and three received it sequentially (P =.95). The mean percentage of lung volume irradiated was 20% in patients who developed radiation pneumonitis and 22% in those who did not (P =.6). For patients treated with CT including paclitaxel, the crude rate of developing radiation pneumonitis was 14.6% (95% confidence interval [CI] = 5.6% to 29.2%). For patients treated with CT without paclitaxel, the crude rate of pneumonitis was 1.1% (95% CI = 0.2% to 2.3%). The difference between the crude rates with or without paclitaxel is highly statistically significant (P<.0001). The mean time to develop radiation pneumonitis in patients treated concurrently with RT and paclitaxel was statistically significantly shorter in patients receiving paclitaxel weekly than in those receiving it every 3 weeks (P =.002). CONCLUSIONS: The use of paclitaxel and RT in the primary treatment of breast cancer should be undertaken with caution. Clinical trials with the use of combination CT, including paclitaxel plus RT, whether concurrent or sequential, must evaluate carefully the incidence of radiation pneumonitis.
Adult↗
Clinical activity of trastuzumab and vinorelbine in women with HER2-overexpressing metastatic breast cancer.
PURPOSE: To determine the response rate and toxicity profile of trastuzumab administered concurrently with weekly vinorelbine in women with HER2-overexpressing advanced breast cancer. PATIENTS AND METHODS: Forty women with HER2-positive (+3 by immunohistochemistry, n = 30; +2 or positive, n = 10) breast cancer were enrolled onto a study of trastuzumab (4 mg/kg x 1, 2 mg/kg weekly thereafter) and vinorelbine (25 mg/m2 weekly, with dose adjusted each week for neutrophil count). Eighty-two percent of women had received prior chemotherapy as part of adjuvant (30%), metastatic (25%), or both (28%) treatment, including substantial portions of patients who had previously received either anthracyclines (20%), taxanes (15%), or both types (38%) of chemotherapy. RESULTS: Responses were observed in 30 of 40 patients (overall response rate, 75%, conditional corrected 95% confidence interval, 57% to 89%). The response rate was 84% in patients treated with trastuzumab and vinorelbine as first-line therapy for metastatic disease, and 80% among HER2 +3 positive patients. High response rates were also seen in women treated with second- or third-line therapy, and among patients previously treated with anthracyclines and/or taxanes. Combination therapy was feasible; patients received concurrent trastuzumab and vinorelbine in 93% of treatment weeks. Neutropenia was the only grade 4 toxicity. No patients had symptomatic heart failure. Grade 2 cardiac toxicity was observed in three patients. Prior cumulative doxorubicin dose in excess of 240 mg/m2 and borderline pre-existing cardiac function were associated with grade 2 cardiac toxicity. CONCLUSION: Trastuzumab in combination with vinorelbine is highly active in women with HER2-overexpressing advanced breast cancer and is well tolerated.
Adult↗
Circulating HER-2/erbB-2/c-neu (HER-2) extracellular domain as a prognostic factor in patients with metastatic breast cancer: Cancer and Leukemia Group B Study 8662.
PURPOSE: The HER-2/erbB-2/c-neu (HER-2) proto-oncogene is a M(r) 185,000 transmembrane tyrosine kinase that is amplified and/or overexpressed by 20-40% of breast cancers. HER-2 has been associated with worse prognosis and resistance or sensitivity to specific treatment. We evaluated circulating levels of extracellular domain of HER-2 (ECD/HER-2) in metastatic breast cancer patients and investigated the prognostic and predictive significance of circulating HER-2 levels regarding endocrine therapy or chemotherapy. EXPERIMENTAL DESIGN: Plasma samples from 242 patients were assayed for circulating ECD/HER-2 levels, using a sandwich enzyme immunoassay. ECD/HER-2 was correlated with clinical data gathered from these patients while they were participating in prospective Cancer and Leukemia Group B (CALGB) therapeutic protocols for metastatic breast cancer. RESULTS: Eighty-nine (37%) of 242 patients had elevated ECD/HER-2 levels (> or =10.5 ng/ml). ECD/HER-2 was significantly associated with tumor burden, progesterone receptor levels, and presence of visceral metastases. Patients with elevated pretreatment levels had a significantly shorter OS but not time-to-progression than did those with ECD/HER-2 levels <10.5 ng/ml in univariate analysis. In univariate but not multivariate subset analyses, among patients treated with endocrine therapy (megestrol acetate), elevated initial ECD/HER-2 was associated with worse OS compared with nonelevated patients. However, among patients treated with chemotherapy (mainly anthracycline-containing regimens), OS did not differ significantly. Rates of response to either endocrine therapy or chemotherapy were similar for patients with elevated and nonelevated ECD/HER-2 levels. CONCLUSIONS: ECD/HER-2 levels are elevated in 35-40% of patients with metastatic breast cancer. Elevated ECD/HER-2 levels are associated with a poorer prognosis in these patients. However, no predictive role for ECD/HER-2 was identified, either for endocrine therapy or for anthracycline-based chemotherapy in the metastatic setting.
Adult↗
Family history is important in estimating coronary risk.
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Aged↗
Predictors of skeletal complications in patients with metastatic breast carcinoma.
BACKGROUND: The high rate of incidence of skeletal complications in women with metastatic breast carcinoma appears to contribute significantly to their morbidity. Although recent trials have demonstrated the efficacy of bisphosphonates in preventing skeletal complications in selected patients, to the authors' knowledge the incidence rate of skeletal complications in an unselected population of women with metastatic breast carcinoma is unknown. The current study was designed to examine the incidence rate of skeletal complications in a large unselected group of women with metastatic breast carcinoma to determine predictors of these complications. METHODS: All women (n = 718) diagnosed with metastatic breast carcinoma between 1981-1991 at the study institution were studied retrospectively. RESULTS: Greater than 50% of the women developed skeletal complications; among these women, 51% had > 1 complication. Approximately 80% of those with bone-limited disease at the time of diagnosis developed complications, as did 60% of those with bone and visceral disease and 21% of those with no bone disease. By univariate analysis, the site of initial metastatic disease, abnormal alkaline phosphatase, and a disease free interval of < 3 years were predictive of skeletal complications. Multivariate analysis revealed that bone involvement at the time of diagnosis was predictive of subsequent skeletal complications. CONCLUSIONS: In this large retrospective study with extensive follow-up, skeletal complications were extremely common and repetitive, although complications predated patient death by >/= 1 year in the group of women presenting with any bone disease. The presence of bone disease at the time of initial presentation was predictive of skeletal complications. In this group of patients, the authors were unable to identify a subgroup with a low rate of skeletal complications.
Bone Diseases↗
An alternative approach for achieving cardiovascular baseline: viewing an aquatic video.
Due to the importance of baseline and recovery levels in the computation of reactivity, two studies were conducted to determine an alternative method to traditional rest for achieving baseline and recovery levels of cardiovascular measurements. Watching a relaxing, aquatic video was compared with a traditional resting baseline to determine the better method for achieving low baseline levels. In addition, watching the video was compared with traditional rest during 5-min post-task recovery periods. Systolic (SBP) and diastolic blood pressure (DBP) decreased more during the baseline period when subjects viewed the video than when subjects rested quietly. Similarly, subjects displayed greater recovery following the mental tasks when they watched a video than when they merely sat quietly. It is recommended that researchers standardize baseline procedures by showing a relaxing video before administering tasks for the assessment of cardiovascular reactivity.
Adult↗
Comparison of the effects of bolus vs. slow infusion of 7.5% NaCl/6% dextran-70 in a model of near-lethal uncontrolled hemorrhage.
Bolus infusion of of 7.5% NaCl/6% dextran-70 (HSD-B) improves outcome from controlled hemorrhage. In contrast, HSD-B during uncontrolled hemorrhage increases bleeding and short-term mortality. The purpose of this study was to compare the effects of bolus vs. slow infusion of HSD in a near-fatal vascular injury hemorrhage model. Sixteen (15-20 kg) swine with 4-mm aortic tears were hemorrhaged to a pulse pressure of 5 mmHg. An ultrasonic flow probe was placed proximal to the aortic tear for continuous blood flow (AF) measurements. Group I (slow infusion; n = 8) was resuscitated with 8 mL/kg of HSD at 0.4 mL/kg/min. Group II (bolus infusion; n = 8) was resuscitated with 8 mL/kg of HSD at 1.33 mL/kg/min. In both groups, HSD infusion was followed by administration of 30 mL/kg of shed blood at 3 mL/kg/min. Hemorrhage volume and 90-min mortality were greater in group II (79+/-11 mL/kg; 75%) compared with group I (43+/-9 mL/kg; 12.5%) (P(Hem) < 0.001; P(Mort) = 0.04). Mean arterial pressure (MAP) and AF were greater in group II compared with group I during the first 15 min of resuscitation. In group I, MAP, AF, cardiac indices, and O2 delivery gradually returned to baseline levels and were significantly greater than group II at 30 min and throughout the remainder of the protocol. In this model of near-lethal uncontrolled hemorrhage, slow infusion of HSD restored cardiodynamics while minimizing hemorrhage volume and mortality. Resuscitation regimens that cause early increases in blood flow and pressure may result in greater hemorrhage and mortality than those regimens that yield comparable flow and pressure increases late in resuscitation.
Animals↗
Docetaxel administered on a weekly basis for metastatic breast cancer.
PURPOSE: To evaluate the safety and efficacy of weekly docetaxel in women with metastatic breast cancer. PATIENTS AND METHODS: Twenty-nine women were enrolled onto a study of weekly docetaxel given at 40 mg/m(2)/wk. Each cycle consisted of 6 weeks of therapy followed by a 2-week treatment break, repeated until disease progression or removal from study for toxicity or patient preference. Fifty-two percent of patients had been previously treated with adjuvant chemotherapy; 21% had received prior chemotherapy for metastatic breast cancer, and 31% had previously received anthracyclines. All patients were assessable for toxicity; two patients were not assessable for response but are included in an intent-to-treat analysis. RESULTS: Patients received a median of 18 infusions, with a median cumulative docetaxel dose of 720 mg/m(2). There were no complete responses. Twelve patients had partial responses (overall response rate, 41%; 95% confidence interval, 24% to 61%), all occurring within the first two cycles. Similar response rates were observed among subgroups of patients previously treated either with any prior chemotherapy or with anthracyclines. An additional 17% of patients had stable disease for at least 6 months. The regimen was generally well tolerated. There was no grade 4 toxicity. Only 28% of patients had any grade 3 toxicity, most commonly neutropenia and fatigue. Acute toxicity, including myelosuppression, was mild. Fatigue, fluid retention, and eye tearing/conjunctivitis became more common with repetitive dosing, although these side effects rarely exceeded grade 2. Dose reductions were made for eight of 29 patients, most often because of fatigue (n = 5). CONCLUSION: Weekly docetaxel is active in treating patients with metastatic breast cancer, with a side effect profile that differs from every-3-weeks therapy.
Adult↗
Mucosa-associated lymphoid tissue lymphoma of the stomach: long term outcome after local treatment.
BACKGROUND: Although antibiotic therapy is emerging as effective initial treatment for patients with gastric lymphoma of mucosa-associated lymphoid tissue (MALT), there is a subset of patients for whom antibiotics are ineffective or inappropriate. Surgical resection can be curative, but total gastrectomy may be required for the eradication of all disease. To identify the optimal nonantibiotic therapy for early stage gastric MALT lymphoma, the authors retrospectively evaluated the Massachusetts General Hospital experience with gastric MALT lymphoma. METHODS: Disease patterns and treatment outcomes were retrospectively analyzed in data from 21 consecutive patients with gastric MALT lymphoma who were treated between 1978 and 1995 at the Massachusetts General Hospital. RESULTS: Sixteen patients were Stage IE, and 5 were in higher stages. Treatment consisted of resection with or without radiation or chemotherapy (14 patients), radiation alone (4 patients), or radiation plus chemotherapy (2 patients). Thirteen Stage IE patients received local therapy only. The 10-year actuarial relapse free survival rate for Stage IE patients was 93%, with 1 relapse among 15 treated patients. Because the patient who relapsed was treated successfully with chemotherapy, the 10-year cancer free survival was 100%. Overall survival for Stage IE patients was 93% at 5 years and 58% at 10 years, with no deaths from lymphoma. CONCLUSIONS: These data indicate that a high probability of long term remission can be achieved with only local treatment of patients with Stage I gastric MALT lymphoma. Preliminary results suggest that radiation therapy is well tolerated and effective and may well be the optimal nonantibiotic treatment for patients with localized gastric MALT lymphoma.
Aged↗
Extracorporeal life support in pulmonary failure after trauma.
OBJECTIVE: To present a series of 30 adult trauma patients who received extracorporeal life support (ECLS) for pulmonary failure and to retrospectively review variables related to their outcome. METHODS: In a Level I trauma center between 1989 and 1997, ECLS with continuous heparin anticoagulation was instituted in 30 injured patients older than 15 years. Indication was for an estimated mortality risk greater than 80%, defined by a PaO2: FIO2 ratio less than 100 on 100% FIO2, despite pressure-mode inverse ratio ventilation, optimal positive end-expiratory pressure, reasonable diuresis, transfusion, and prone positioning. Retrospective analysis included demographic information (age, gender, Injury Severity Score, injury mechanism), pulmonary physiologic and gas-exchange values (pre-ECLS ventilator days [VENT days], PaO2:FIO2 ratio, mixed venous oxygen saturation [SvO2], and blood gas), pre-ECLS cardiopulmonary resuscitation, complications of ECLS (bleeding, circuit problems, leukopenia, infection, pneumothorax, acute renal failure, and pressors on ECLS), and survival. RESULTS: The subjects were 26.3+/-2.1 years old (range, 15-59 years), 50% male, and had blunt injury in 83.3%. Pulmonary recovery sufficient to wean the patient from ECLS occurred in 17 patients (56.7%), and 50% survived to discharge. Fewer VENT days and more normal SvO2 were associated with survival. The presence of acute renal failure and the need for venoarterial support (venoarterial bypass) were more common in the patients who died. Bleeding complications (requiring intervention or additional transfusion) occurred in 58.6% of patients and were not associated with mortality. Early use of ECLS (VENT days < or = 5) was associated with an odds ratio of 7.2 for survival. Fewer VENT days was independently associated with survival in a logistic regression model (p = 0.029). Age, Injury Severity Score, and PaO2:FIO2 ratio were not related to outcome. CONCLUSION: ECLS has been safely used in adult trauma patients with multiple injuries and severe pulmonary failure. In our series, early implementation of ECLS was associated with improved survival. Although this may represent selection bias for less intractable forms of acute respiratory distress syndrome, it is our experience that early institution of ECLS may lead to improved oxygen delivery, diminished ventilator-induced lung injury, and improved survival.
Adolescent↗
Research fundamentals: V. The use of laboratory animal models in research.
Animal research has provided important information about many aspects of the pathophysiology of human disease. Well-performed animal studies can determine the potential benefit of many proposed therapeutic interventions, and experimental results from animal studies have served as the basis for many landmark clinical trials. Many animal research models are described in the research literature, and choosing the appropriate model to answer a research question can be a daunting task. Even more challenging is developing a new model when none of the existing systems are relevant to the proposed question. This article was prepared by members of the SAEM Research Committee to provide an overview of animal modeling. Important considerations in choosing, applying, and developing animal research models are outlined. Practical discussions of potential problems with animal models are also provided.
Animals↗
A staff dialogue on do not resuscitate orders: psychosocial issues faced by patients, their families, and caregivers.
Shortly before his death in 1995, Kenneth B. Schwartz, a cancer patient at Massachusetts General Hospital (MGH), founded The Kenneth B. Schwartz Center at MGH. The Schwartz Center is a non-profit organization dedicated to supporting and advancing compassionate health care delivery which provides hope to the patient, support to caregivers, and encourages the healing process. The Center sponsors the Schwartz Center Rounds, a monthly multidisciplinary forum where caregivers reflect on important psychosocial issues faced by patients, their families, and their caregivers, and gain insight and support from fellow staff members. The following case of a woman who developed lymphoma was discussed at the July and August, 1997 Schwartz Center Rounds. There were considerable delays and uncertainties in the diagnosis, which was followed by an unpredictably chaotic clinical course. Although she had made it clear to her doctor that she did not want "heroic measures," she had unexpectedly rallied so many times that her son and her husband wanted her doctors to do everything possible to keep her alive, including the performance of cardiopulmonary resuscitation (CPR). The clinical benefit of CPR in the event of cardiac arrest in those with cancer is discussed, as are do not resuscitate (DNR) orders, living wills, and healthcare proxies. In addition, the issues that surround DNR status, including who should discuss DNR status with a patient, and how and when it should be discussed, are reviewed. Staff raised concerns about the effect of discussing DNR status on the doctor-patient relationship, and wondered whether writing DNR orders adversely affect the care of patients.
Advance Directives↗
Alternating chemotherapy regimens for patients with metastatic breast cancer. A pilot study based on tumor marker kinetics. Cancer and Leukemia Group B.
BACKGROUND: Chemotherapy is most effective when applied during the biologically active stage of tumor cells. According to the authors' previous tumor marker kinetic study, methotrexate plus 5-fluorouracil (MF) was found to yield either a cytolytic effect in an MF-sensitive tumor cell population or a cytostatic effect in an MF-resistant population. In the latter, the suppressive effect was transient and the biologic activity resumed in one week after MF administration. METHODS: Based on this marker kinetic study, an alternating chemotherapy program was designed to study its antitumor and side effects. Methotrexate (M) (200 mg/m2) and 5-fluorouracil (F) (500 mg/m2) were administered intravenously on day 1 followed 24 hours later by leucovorin (L) (10 mg/m2 orally every 6 hours for 6 doses). Cyclophosphamide (C) 300 (mg/m2), doxorubicin (A) (50 mg/m2), and vincristine (V) (1 mg/m2) were given on day 8. The MFL/CAV was given every 4 weeks. RESULTS: Forty-nine patients with metastatic breast cancer were enrolled; 41 were eligible. There were 5 complete and 23 partial remissions, producing a total response rate of 68%. In 15 patients with liver metastases, the response rate was 73% and the median survival 13.7 months, results superior to those previously reported for this subgroup of patients. Side effects were manageable. CONCLUSIONS: This regimen, which can be given safely in an outpatient setting, yielded encouraging response and survival rates in patients with visceral-dominant disease with poor prognoses.
Adult↗
The relationship of health locus of control and cardiac rehabilitation to mastery of illness-related stress.
The study examined the relationships among participation in outpatient rehabilitation, health locus of control, and mastery of stress with coronary artery disease completed the Master of Stress Instrument (MSI) and the Multidimensional Health Locus of Control Scale. One fourth of the sample had participated in the hospital's cardiac rehabilitation programme. Results showed no difference between cardiac-rehabilitation participants and nonparticipants on mastery, internal locus of control or stress. Demographic characteristics of age, education, race and gender revealed no significant correlation with either the total MSI score or its component measures. However, internal locus of control was significantly and positively correlated to both growth and total mastery. A stronger relationship was found between internal locus of control and change. This finding supports the hypothesis that health-internals achieve higher levels of mastery.
Adaptation, Psychological↗
Rationale for routine axillary dissection in carcinoma of the breast.
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Breast Neoplasms↗