A dosimetric analysis of tomotherapy based intensity modulated radiation therapy with and without bone marrow sparing in gynecologic malignancies.

Whole pelvic radiotherapy with concurrent chemotherapy is the standard of care for locally advanced cervical carcinoma. Published literature reports that the pelvic bone marrow (BM) dosimetric parameters of V10 > 90% and V20 > 80% are associated with higher rates of hematologic toxicities using this approach. Here, we investigate the ability of Tomotherapy based intensity modulated radiation therapy (IMRT) to reduce dose to pelvic BM while evaluating dose distribution to critical structures and planning target volume (PTV) coverage. Ten patients were selected for analysis. Normal structures, whole pelvic BM, PTV contours, and IMRT objects were standardized. Two whole pelvis Tomotherapy plans were created for each patient, one standard plan, and one with the addition of a BM sparing (BMS) constraint (V10 <85%, V20 < 80%). Data were calculated from multiple points with regard to BM dose, normal structure dose, and PTV coverage. Differences in dose distributions between the two sets of plans were analyzed using a paired t-test. The addition of a BMS planning constraint resulted in significant decreases in pelvic BM dose at the following dosimetric points: V5, V10, V15, V20, V30, V40, V50, and mean dose (p < 0.05 for all points). There were no significant differences in dose to small bowel, bladder or rectum, with the exception of one data point (small bowel V30, p = 0.004) between the two sets of plans. There was no sacrifice of PTV coverage or loss of homogeneity with the addition of a BMS planning constraint. BMS-IMRT significantly reduces radiation dose to the pelvic BM while maintaining the ability to spare dose to the small bowel, bladder and rectum. The planning constraints were met without violation of study criteria, and without sacrifice of PTV coverage. Further investigation is warranted to determine if rates of hematologic toxicity improve with utilization of Tomotherapy based BMS-IMRT.

Patient-oriented learning: a review of the role of the patient in the education of medical students.

AIM: To explore the contribution patients can make to medical education from both theoretical and empirical perspectives, to describe a framework for reviewing and monitoring patient involvement in specific educational situations and to generate suggestions for further research. METHODS: Literature review. RESULTS: Direct contact with patients can be seen to play a crucial role in the development of clinical reasoning, communication skills, professional attitudes and empathy. It also motivates through promoting relevance and providing context. Few studies have explored this area, including effects on the patients themselves, although there are examples of good practice in promoting more active participation. CONCLUSION: The Cambridge framework is a tool for evaluating the involvement of patients in the educational process, which could be used by curriculum planners and teachers to review and monitor the extent to which patients are actively involved. Areas for further research include looking at the 'added value' of using real, as opposed to simulated, patients; more work on outcomes for patients (other than satisfaction); the role of real patients in assessment; and the strengths and weaknesses of different models of patient involvement.

The effect of hypercapnia and hypoxemia on the cardiovascular responses to isoproterenol.

BACKGROUND: The reason for the increased risk of death with fenoterol and isoproterenol in asthma is unknown but may relate to their cardiovascular effects. Deaths from asthma usually occur outside hospital where hypoxemia, with or without hypercapnia, may exist. Both of these states can influence the cardiovascular system. We investigated whether different gas mixtures modified the cardiovascular effects of isoproterenol. METHOD: Nine healthy men were randomly assigned to receive each of three gas mixtures to achieve (1) normoxia-normocapnia, (2) hypercapnia (end-tidal PaCO2, 50 mm Hg), (3) hypoxemia-hypercapnia (arterial oxygen saturation, 90%; PaCO2, 50 mm Hg). Isoproterenol was administered with each of the gas mixtures. Cardiovascular measurements of heart rate, blood pressure, cardiac index, ejection fraction, fractional shortening, electromechanical systole, and the QTc interval were made before administration of the gases, as well as before and 5 minutes after isoproterenol administration. RESULTS: The changes after hypercapnia were not significantly different from those after normoxia-normocapnia. Hypoxemia-hypercapnia increased heart rate, systolic and diastolic blood pressure, QTc interval, cardiac index, ejection fraction, and fractional shortening. Isoproterenol increased heart rate, systolic blood pressure, QTc interval, cardiac index, ejection fraction, and fractional shortening while the subjects breathed the normoxia-normocapnia gas mixture. It caused similar changes with the other gas mixtures. The changes were additive. CONCLUSION: Isoproterenol and hypoxemia-hypercapnia will increase myocardial oxygen demand and could prove to be detrimental in severe asthma.

Mitral valve repair: a clinical and echocardiographic study.

OBJECTIVE: To evaluate the clinical and echocardiographic results of mitral valve repair done within an 11 year period. DESIGN: Retrospective review of case notes and clinical and echocardiographic examination of survivors. Analysis was made according to the intention to treat principle. PATIENTS: A consecutive series of 94 patients with mitral valve disease who had mitral reconstruction between 1980 and 1991. INTERVENTIONS: Mitral repair according to the techniques of Carpentier or Duran. MAIN OUTCOME MEASURES: Operative mortality, actuarial survival, rates of freedom from reoperation, thromboembolism, infective endocarditis, clinical state, and echocardiographic findings. RESULTS: There were equal numbers of males and females (mean (range) age 49 (4-74) years). The aetiology of mitral disease was degenerative in 59% and rheumatic in 30% of the patients. Operative mortality was 3%. The 10 year actuarial and valve related survival rates were 67% and 75%. At 10 years, 84% of the patients were free from thromboembolism, 94% free from haemorrhage related to anticoagulation, 88% free from infective endocarditis, and 73% free from reoperation. Of 75 survivors with completed follow up, 96% were in New York Heart Association functional class I or II and 64% were in sinus rhythm. Of 55 survivors who had an echocardiogram at follow up, normal left ventricular end diastolic dimension was shown in 76% and normal left ventricular shortening fraction in 89%. Doppler studies showed no mitral regurgitation in 36%, trivial or mild in 42%, moderate in 14%, and severe in 7% of patients. In stepwise logistic analysis previous myocardial infarction was associated with poor outcome (odds ratio: 13.7, p < 0.05). CONCLUSION: The results are comparable with similar studies and support the value of mitral valve repair. There is reservation about the use of repair for patients with previous myocardial infarction.

Nonspecific systolic murmurs: an audit of the clinical value of echocardiography.

AIM: To evaluate the clinical use of echocardiography in patients with nonspecific systolic murmurs. METHODS: Analysis of request forms and echocardiogram reports in a consecutive series of scans done for patients with nonspecific systolic murmurs between 1984 and 1991. RESULTS: Normal cardiac structure and function were found in: (1) 62% of 565 studies done for patients with nonspecific systolic murmurs; (2) 96% of 69 scans in patients with clinical diagnosis of a benign murmur and (3) 93% of 45 pregnant women with nonspecific systolic murmurs. No echocardiographic abnormalities were detected in 76% of studies done for patients aged between 1 and 50 yr. Congenital heart disease was found in 39% of patients with nonspecific systolic murmurs aged between 0 and 1 yr. Mitral regurgitation was found in 33% and aortic valve disease in 22% of nonspecific systolic murmurs patients aged over 60 yr. CONCLUSIONS: Echocardiography rarely revealed significant abnormalities in the assessment of patients with nonspecific systolic murmurs aged between 1 and 50 yr, especially when the test was used to confirm the clinical suspicion that the heart was normal. Ultrasound scanning was useful in the assessment of nonspecific murmurs in patients aged 0-1 yr or over 50 yr, particularly those over 60 yr.

Cardiovascular effects of fenoterol under conditions of hypoxaemia.

BACKGROUND: The reason for the association of increased risk of death with fenoterol in patients with asthma in New Zealand is unknown but may relate to its cardiovascular effects. Most deaths from asthma occur outside hospital, where hypoxaemia is likely to be a complicating factor. The cardiovascular effects of fenoterol have been investigated therefore under conditions of normoxaemia and hypoxaemia. METHOD: Eight healthy men were studied on two occasions. Measurements of heart rate, blood pressure, total electromechanical systole (QS2I), electrocardiographic QTc interval, cardiac index, stroke volume, and ejection fraction were made under conditions of normoxaemia and hypoxaemia (arterial oxygen saturation 90%) before and after administration of 800 micrograms of fenoterol by a metered dose inhaler. The order in which treatments were applied was according to a Latin square design. RESULTS: Before inhalation of fenoterol hypoxaemia was associated with a significant increase in heart rate (8 beats/min) and QTc interval (15.6 ms). Under conditions of normoxaemia fenoterol caused a significant increase in heart rate (14.3 beats/min), systolic blood pressure (7.7 mm Hg), stroke volume (27.7 ml), cardiac index (1.6 1/min/m2), ejection fraction (11.48), and QTc interval (32.9 ms) and a fall in QS2I (-23.2 ms) and diastolic blood pressure (-8.4 mm Hg). Under conditions of hypoxaemia the changes after inhalation of fenoterol were similar to those recorded during normoxaemia; thus the effects of hypoxaemia and fenoterol were additive (heart rate 21.9 beats/min, QTc 43.5 ms with fenoterol and hypoxaemia). CONCLUSION: The chronotropic and electrophysiological effects of fenoterol were enhanced by conditions of hypoxaemia.

How is echocardiography used? An audit of 11,701 studies.

OBJECTIVE: to review the utilisation of 2-D and Doppler echocardiography between 1984 and 1990. METHODS: analysis of request forms and echocardiogram reports for patient demographics, major clinical indications and principal echocardiogram findings. RESULTS: between May 1984 and December 1990 11,701 studies were done in 8101 patients. Requests for scans increased by an average of 225 per year. Most frequently scanned were male (55%), inpatients (52%) and patients aged 60-69 yr (19%). In 1984 cardiologists made 100% of the requests and did 78% of the studies. In 1990 noncardiologists requested 48% of scans and 91% of studies were done by technicians. Echocardiograms were requested most often for assessment of valve disease (39%), left ventricular function (18%) and congenital heart disease (15%). Thirty-five percent of studies showed valve disease, 17% myocardial disorders and 10% congenital heart disease. Normal findings were shown in 25%. CONCLUSION: in this 6.5 year period there was a rapid increase in the utilisation of echocardiography and the practice changed from one requested by and done by cardiologists to a generally available service provided by technicians. The greatest application for scanning was in the assessment of acquired valvar disease and myocardial disorders. One-quarter of echocardiograms showed normal cardiac structure and function.

Inheritance of atrioventricular conduction time in Tokelau Islanders.

The inheritance of A-V conduction time in Polynesians has been examined, using ECGs taken from the population of the Tokelau Islands. As has been demonstrated in other racial groups, A-V conduction time was influenced by sex, age, and heart rate. Complex segregation analysis provides evidence for a significant polygenic influence on A-V conduction, but no evidence for a major gene. Familial correlations and commingling analysis are in agreement with this conclusion. The heritability of A-V conduction time was 0.46. The hypothesis of Møller & Heiberg (1980a) that a major gene could be influencing A-V conduction, is not supported by these data.

Exercise heart rates at different serum digoxin concentrations in patients with atrial fibrillation.

Heart rate at rest and during increasing workloads was measured in a double blind study of 12 patients with chronic atrial fibrillation when serum concentrations of digoxin were nil and at low and high therapeutic values. Twelve normal subjects were studied for comparison. The heart rate at all levels of exercise in most patients with atrial fibrillation was not adequately controlled by any serum digoxin concentration tested despite a reduction in heart rate with increasing serum digoxin concentrations. Control of the resting heart rate, even in patients with high serum digoxin concentrations, did not ensure adequate control of the heart rate during work rates equivalent to regular daily activities.

Subacute massive pulmonary embolism.

Twenty-four patients with subacute massive pulmonary embolism were studied both during their initial illness and up to nine years after it. The most common mode of presentation was progressive dyspnoea over a two to 12 week period, which in some, but not all, patients was accompanied by pleuritic chest pain and haemoptysis. Physical signs at diagnosis usually suggested right heart strain and ventilation/perfusion mismatch and in the five patients with the highest pulmonary artery pressures the pulmonary component of the second sound was accentuated. The chest x-ray and electrocardiogram provided useful diagnostic information in most patients though occasionally they were normal. Early response to thrombolytic treatment was poor when compared with patients with acute pulmonary embolism but was occasionally dramatically successful, and heparin alone provided satisfactory treatment in the eight patients receiving it. Pulmonary embolectomy provided poor results and four of the five patients undergoing this form of treatment died. Nine patients died during the initial illness and in seven death was directly related to embolic disease. One patient died from neoplastic disease during follow-up. Though the prolonged illness, poor initial response to treatment, and absence of predisposing factors suggest that recurrent embolic disease and late pulmonary hypertension might occur three was no evidence of this during a follow-up period of one to nine years (median five years).

The clinical value of digoxin in patients with heart failure and sinus rhythm.

Six patients in sinus rhythm with congestive heart failure due to either myocardial infarction or cardiomyopathy, were given oral frusemide to eliminate oedema. Symptomatic relief occurred as body weight was reduced, and after a 'dry' basal weight had been achieved, progressive-load exercise testing was done to examine any benefit that derived from adding oral digoxin to the diuretic. Three pairs of sub-maximal exercise tests were done at intervals over three months, and the responses of each patient when using digoxin and diuretics were compared with those when using diuretics alone. One patient did not complete this study, because more frequent premature beats and increased angina followed the withdrawal of digoxin. For the five patients who completed three pairs of tests, there was no significant change in symptoms, in workload achieved, or in heart rate, respiratory rate, ventilation and respiratory quotient, whether digoxin was added or removed. It is concluded that in these patients where salt and water retention was controlled with diuretics, digoxin did not improve the capacity for exercise, and it is suggested that for such patients with myocardial disease in sinus rhythm, treatment should begin with diuretics.

Gas-liquid chromatographic method for the routine estimation of disopyramide in plasma or serum.

A rapid, sensitive and specific gas-liquid chromatographic method is presented for the routine monitoring of plasma concentrations of the anti-arrhythmic compound, disopyramide. The procedure involves extraction of the drug from alkaline plasma into ether, purification of the extract and gas chromatographic analysis using OV-101 liquid phase and flame ionization detection. The results demonstrate the accuracy and reproducibility of the method. Contrary to a previous report, it has been shown that delay in separating plasma from erythrocytes does not affect the disopyramide level in plasma.