The adequacy of tissue microarrays in the assessment of inter- and intra-tumoural heterogeneity of infiltrating lymphocyte burden in leiomyosarcoma.

The characterisation and clinical relevance of tumour-infiltrating lymphocytes (TILs) in leiomyosarcoma (LMS), a subtype of soft tissue sarcoma that exhibits histological heterogeneity, is not established. The use of tissue microarrays (TMA) in studies that profile TIL burden is attractive but given the potential for intra-tumoural heterogeneity to introduce sampling errors, the adequacy of this approach is undetermined. In this study, we assessed the histological inter- and intra-tumoural heterogeneity in TIL burden within a retrospective cohort of primary LMS specimens. Using a virtual TMA approach, we also analysed the optimal number of TMA cores required to provide an accurate representation of TIL burden in a full tissue section. We establish that LMS have generally low and spatially homogenous TIL burdens, although a small proportion exhibit higher levels and more heterogeneous distribution of TILs. We show that a conventional and practical number (e.g. ≤3) of TMA cores is adequate for correct ordinal categorisation of tumours with high or low TIL burden, but that many more cores (≥11) are required to accurately estimate absolute TIL numbers. Our findings provide a benchmark for the design of future studies aiming to define the clinical relevance of the immune microenvironments of LMS and other sarcoma subtypes.

Practical aspects of risk assessment in gastrointestinal stromal tumors.

INTRODUCTION: Gastrointestinal stromal tumors (GISTs) are mesenchymal tumors of the gastrointestinal tract, which are characterized in the majority of cases by activating mutations in KIT and platelet-derived growth factor receptor alpha (PDGFRA). The introduction of tyrosine kinase inhibitors has revolutionized the management of patients with metastatic GIST. However, complete surgical resection remains the mainstay of management for those with localized disease. Recently, three large trials have confirmed the benefit of adjuvant imatinib therapy in patients who were at high risk of recurrence following complete resection. In this setting, it is critical that oncologists understand the various GIST risk assessment criteria and be able to apply these methods to accurately assess the risk of recurrence and the need for adjuvant imatinib therapy. PURPOSE: The aim of this review is to outline the risk stratification systems currently available to oncologists who are treating patients with GIST, so they can be optimally applied for clinical decision-making.

The master potter and the rejected pots: eugenic legislation in Victoria, 1918-1939.

In the period since Carol Bacchi introduced eugenics into Australian historiography in 1980, much has been written that has increased our understanding of the role eugenics played in the development of Australian society in the first half of this century. It is now generally recognised that eugenics developed after the first world war from a relatively simplistic scientific justification of racist and class-biased social Darwinism into a movement concerned with using environmental reforms to help a wide range of Australians reach their full potential. In the interwar years the reform eugenicists (as they have been named) were active in a wide range of environmental movements including health reforms, slum clearance and educational improvements. The corollary of reform eugenics was based on the belief that heredity was an impassable obstacle for some: mental deficients were not considered to be racially 'fit' or 'efficient' enough to benefit from the reforms. Whilst this side of reform eugenics is well known in other countries (sterilisation programmes in Germany, the United States and Scandinavia being examples), it is yet to receive much attention so far in the discussion about Australia in the interwar years. This article argues that the attempt of a group of influential reform eugenicists in Victoria in the interwar years to institute legislation aimed at denying a significant proportion of the population the most basic rights of citizenship (including the right to reproduce) redresses the imbalance in our understanding of reform eugenics in the interwar years.

CT assessment of jugular foramen dominance and its association with hand preference.

Three hundred and seven normal CT scans of the head were prospectively analysed to assess jugular foramen dominance. After assessment, hand preference was elicited. Of these, 276 were right-handed and 31 were left-handed. Of the right-handed patients: 180 had a larger jugular foramen on the right; 63 had a larger jugular foramen on the left; and in 33 no difference could be discerned. Of the left-handed patients: 11 had a larger jugular foramen on the right; 16 had a larger jugular foramen on the left; and in four no difference could be discerned. The results suggested a significant association between jugular foramen dominance and hand preference.

An assessment of practice support and continuing medical education needs of rural Pennsylvania family physicians.

Family physicians provide the greatest proportion of care in rural communities. Yet, the number of physicians choosing family practice and rural practice has continued to decline. Undesirable aspects of rural practice, such as professional isolation and a lack of or inadequate resources, are assumed to be associated with this decline. This article reports on the practice support and continuing medical education needs of rural family physicians. A mail survey was conducted in 1993 on a purposive sample of family physicians in 39 of 67 rural-designated or urban Pennsylvania counties with low population densities. The physicians identified needs that included patient education materials and programs, community health promotion, federal regulation updates, technical assistance with computers and business management, database software and a videotape lending library, a drug hotline, and mini-fellowships on clinical skill development. A majority of respondents were willing to participate in clinical educational experiences for students and residents. Some physicians indicated a lack of interest in access to information through telecommunications, e.g., video conference referrals and consultations. Overall, findings revealed that family physicians need and are receptive to a variety of practice support and continuing education programs. A practice support program coupled with policy coordination among public and private organizations is likely to lessen complaints by rural primary care physicians.

Formal assessment of the surgical trainee: a review of eight years experience at St Lawrence Hospital, Chepstow.

In light of the proposals for a continuum of higher surgical training, we reviewed an 8-year experience of formal assessments of surgical trainees. We undertook a retrospective analysis of 34 completed assessment forms, retrieved from records, and a postal questionnaire of 54 former (and current) trainees. Our study revealed that all trainees agreed in principle with formal assessments. Eighty-one per cent found their assessment either useful or excellent and a further 17 per cent found the advice received was influential in their careers. The consultants, in turn, were able to modify the training programme as a result of constructive feedback. Based on our experience we recommend formal assessments of surgical trainees as an important and rewarding part of an impartial peer review system within a continuum of higher surgical training.

Influence of income, hours worked, and loan repayment on medical students' decision to pursue a primary care career.

OBJECTIVE: To assess the specialty plans of current fourth-year medical students and, for those not choosing primary care specialties, to investigate the potential effect that changes in key economic or lifestyle factors could have in attracting such students to primary care. DESIGN AND PARTICIPANTS: A survey study was sent to 901 fourth-year medical students in the 1993 graduating classes of six US medical schools. OUTCOME MEASURES: Comparisons were made between students choosing and not choosing primary care specialties. For the non-primary care students, we also evaluated whether alteration of income, hours worked, or loan repayment could attract them to primary care careers. RESULTS: Of the 688 responses (76% response rate), primary care specialties were chosen by 27% of the students and non-primary care specialties by 73%. One quarter (25%) of the non-primary care students indicated they would change to primary care for one of the following factors: income (10%), hours worked (11%), or loan repayment (4%). For students whose debt was $50,000 or greater, the loan repayment option became much more important than for students with lesser debt. In all, a total of 45% (n = 313) of the students indicated either they were planning to enter primary care (n = 188) or they would change to a primary care specialty (n = 125) with appropriate adjustments in income, hours worked, or loan repayment. CONCLUSION: Significant changes in economic and lifestyle factors could have a direct effect on the ability to attract students to primary care. Including such changes as part of health system reform, especially within the context of a supportive medical school environment, could enable the United States to approach a goal of graduating 50% generalist physicians.

Predictive equation for assessing energy expenditure in mechanically ventilated critically ill patients.

Traditional formulas, such as the Harris and Benedict equation (HBE), do not accurately predict energy expenditure (EE) in mechanically ventilated, critically ill patients (MVCIP). The purpose of this study was to develop a predictive EE equation to assess EE requirements in MVCIP. A portable metabolic cart was used to measure indirectly EE in 112 MVCIP. Patients were studied at rest and for 30 min on the first or second day of ICU admission. No nutrition was received during the study period. Variables investigated were: age, BSA, Acute Physiology and Chronic Health Evaluation (APACHE II) score, sepsis score, Injury Severity Score (ISS), respiratory rate (f), tidal volume (VT), minute ventilation, mean arterial pressure, heart rate, body temperature (Temp), and outcome. Patient age, APACHE II score, sepsis score, ISS, and BSA were 50 +/- 20 yr, 16 +/- 7, 11 +/- 6, 32 +/- 14, and 1.80 +/- 0.27 m2, respectively. Correlation and multiple regression analyses were used with EE as the dependent variable. A predictive equation (EE [kcal/day] = 945 BSA -6.4 age + 108 Temp + 24.2 f + 817 VT -4349) was determined from variables that contributed greater than 3% to the variance of EE: BSA (52%), age (10%), f (5%), VT (5%), and Temp (3%). The HBE underestimated measured EE by 34 +/- 19% and in 79 patients deviated greater than 15%. Using the new equation, only 15 patients' EE deviated greater than 15% from measured EE. The new predictive EE equation can accurately assess EE in MVCIP.

Energy expenditure associated with CPAP and T-piece spontaneous ventilatory trials. Changes following prolonged mechanical ventilation.

The use of portable metabolic carts to assess energy expenditure (EE) by measuring oxygen consumption (VO2) and carbon dioxide production (VCO2) has recently been applied to patients undergoing weaning from mechanical ventilation. The VO2 and EE can be used to estimate changes in the work of breathing (WOB) associated with different weaning strategies. The purpose of this study was to use VO2 and EE to assess changes in the WOB when assisted mechanical ventilation (AMV) was replaced with two spontaneous ventilatory trial (SVT) techniques: continuous positive airway pressure (CPAP) and T-piece. Nine difficult-to-wean patients were studied during the initial weaning period following 26 +/- 18 days (mean +/- SD) of mechanical ventilatory support. The VO2 and EE during all AMV were 296 +/- 75 ml/min and 2069 +/- 519 kcal/day, respectively. Compared to the baseline AMV levels, during CPAP overall VO2 and EE increased 14 percent and 13 percent, respectively, and during T-piece overall VO2 and EE increased 20 percent and 19 percent, respectively. Respiration rate (f) increased and tidal volume (VT) decreased during both SVTs compared to AMV although no significant change in minute ventilation was seen. The WOB, as judged from changes in VO2, was only 5 percent higher during T-piece compared to CPAP; however, patients tolerated an average of only 141 +/- 45 min on T-piece vs 165 +/- 29 minutes on CPAP. We conclude that during the initial weaning stages in patients who have received prolonged mechanical ventilatory support, the WOB associated with SVTs is increased compared to AMV but that the WOB associated with T-piece is not significantly greater than that for CPAP.

Effect of routine administration of analgesia on energy expenditure in critically ill patients.

Measurement of gas exchange using portable metabolic carts to indirectly determine energy expenditure (EE) has been a recent advance in the nutritional management of mechanically ventilated, critically ill patients. Although administration of large doses of morphine has been shown to significantly decrease EE, the influence on EE of morphine given in routine amounts to critically ill patients has not been studied previously. We examined the effect of morphine administration (given as bolus IV injections of 0.10 mg/kg every two hours and continuous IV infusion at 0.05 mg/kg/hr) on EE during rest and various ICU activities in seven mechanically ventilated patients. Morphine administration resulted in a significant reduction in resting EE and total EE of 6.0 and 8.6 percent, respectively. However, EE associated with activities (ie, chest x-ray examination and chest physiotherapy) were not significantly affected by morphine administration. Both bolus and continuous IV morphine infusion had similar effects on EE. Administration of routine doses of morphine significantly decreases total EE in critically ill patients. This should be considered an important factor influencing measurements of EE.

Twenty-four hour energy expenditure in critically ill patients.

Resting energy expenditure (EE) is often used as the basis of nutritional support for critically ill patients but whether resting EE is representative of total daily EE is not known. EE was measured for 24 h in ten mechanically ventilated, critically ill patients (average Acute Physiology and Chronic Health Evaluation II score 23) to determine EE, resting EE, and the energy expended during various ICU activities. Although activities, such as weighing the patient on a sling-type bed scale, repositioning, and chest physiotherapy resulted in dramatic EE increases above resting levels (36%, 31%, and 20%, respectively), the actual contribution of these activities to total EE was small (1.1%, 2.1%, and 3.6%, respectively). The mean measured resting EE was 47.3 +/- 22.3% above mean predicted EE based on the Harris and Benedict equation, and the mean total 24-h EE was 6.9 +/- 2.6(SD)% above the mean measured resting EE. In this group of mechanically ventilated, critically ill patients, an activity factor of no greater than 10% above resting EE is appropriate.