Inflammasome-dependent IL-1ß release depends upon membrane permeabilisation.

Interleukin-1ß (IL-1ß) is a critical regulator of the inflammatory response. IL-1ß is not secreted through the conventional ER-Golgi route of protein secretion, and to date its mechanism of release has been unknown. Crucially, its secretion depends upon the processing of a precursor form following the activation of the multimolecular inflammasome complex. Using a novel and reversible pharmacological inhibitor of the IL-1ß release process, in combination with biochemical, biophysical, and real-time single-cell confocal microscopy with macrophage cells expressing Venus-labelled IL-1ß, we have discovered that the secretion of IL-1ß after inflammasome activation requires membrane permeabilisation, and occurs in parallel with the death of the secreting cell. Thus, in macrophages the release of IL-1ß in response to inflammasome activation appears to be a secretory process independent of nonspecific leakage of proteins during cell death. The mechanism of membrane permeabilisation leading to IL-1ß release is distinct from the unconventional secretory mechanism employed by its structural homologues fibroblast growth factor 2 (FGF2) or IL-1α, a process that involves the formation of membrane pores but does not result in cell death. These discoveries reveal key processes at the initiation of an inflammatory response and deliver new insights into the mechanisms of protein release.

Audiovisual distraction reduces pain perception during aural microsuction.

INTRODUCTION: Aural microsuction is a common ear, nose and throat procedure used in the outpatient setting. Some patients, however, find it difficult to tolerate owing to discomfort, pain or noise. This study evaluated the effect of audiovisual distraction on patients' pain perception and overall satisfaction. METHODS: A prospective study was conducted for patients attending our aural care clinic requiring aural toileting of bilateral mastoid cavities over a three-month period. All microsuction was performed by a single clinical nurse specialist. Any patients with active infection were excluded. For each patient, during microsuction of one ear, they watched the procedure on a television screen while for the other ear they did not view the procedure. All patients received the same real time explanations during microsuction of both ears. After the procedure, each patient completed a visual analogue scale (VAS) to rate the pain they experienced for each ear, with and without access to the television screen. They also documented their preference and reasons why. RESULTS: A total of 37 patients were included in the study. The mean pain score for patients viewing the procedure was 2.43 compared with a mean of 3.48 for patients with no television view. This difference in patients' pain perception was statistically lower in the group who observed the procedure on the television (p=0.003), consistent with the majority of patients reporting a preference to viewing their procedure (65%). CONCLUSIONS: Audiovisual distraction significantly lowered patients' VAS pain scores during aural microsuction. This simple intervention can therefore reduce patients' perceived pain and help improve acceptance of this procedure.

Prolonged hyperphagia with high-fat feeding contributes to exacerbated weight gain in rats with adult-onset obesity.

Leptin-resistant rats, when given a high-fat (HF) diet, have a delayed normalization of caloric intake and greater weight gain than those on a chow diet. Because aged, obese rats are leptin resistant, these data predict that they will also have a delayed normalization of caloric intake and exacerbated weight gain when provided a HF diet. To investigate this hypothesis, along with the consequences of a HF diet on voluntary wheel running, we compared various ages of rats on a HF or chow diet. HF-fed young rats spontaneously divided into diet-induced obese and diet-resistant rats. However, all aged rats were susceptible to the weight-gaining effects of HF feeding. Rate of initial weight gain was proportional to age, and peak caloric intake on the HF diet and the days required to normalize caloric intake to basal levels increased with age. Responsiveness to peripheral leptin before HF feeding revealed a dose-response decrease in food intake and body weight in the young but no responses in the aged to even the highest dose, 0.5 mg/day. In addition, both age and HF feeding decreased the tendency for wheel running, suggesting the propensity for inactivity with age and HF feeding may contribute to age-related obesity and accelerate the rate of diet-induced obesity. These results demonstrate that aged rats are more susceptible to the detrimental effects of a HF diet.

Real-time calibration of temperature estimates during radiofrequency ablation.

Radiofrequency ablation is an interstitial focal ablative therapy that can be used in a percutaneous fashion and permits in situ destruction of hepatic tumors. Recurrence rates after rf therapy are as high as 34-55%, due to difficulties in accurately identifying the zone of necrosis (thermal lesion) because of the low intrinsic acoustic contrast between normal and ablated liver tissue. Our goal is to provide real-time ultrasonic tracking of temperature changes over the large range of temperatures traditionally used (40-100 degrees C) in rfablation procedures using an external ultrasound transducer. Temperature estimates are obtained using a cross-correlation algorithm applied to rf ultrasound echo signal data acquired at discrete intervals during heating. Apparent tissue displacement estimates obtained at these discrete time-intervals are accumulated to obtain a cumulative displacement map, whose gradient provides after appropriate scaling provides a temperature map at the specified elapsed ablation duration. Temperature maps are used to display the initial temperature rise and to continuously update a thermal map of the treated region. In this paper, we develop calibration curves that relate the echo shift due to the change in the speed of sound and thermal expansion to the corresponding temperature increase on in-vitro tissue specimens. These calibration curves can then be utilized for the real time calibration and analysis of temperature estimates obtained from the rf echo signals during ablation. Temperature maps obtained using the calibration curve compare favorably to temperature estimates observed using the invasive thermosensor readings on the ablation electrode and previous results that utilized a linear calibration factor.

Monarch larvae sensitivity to Bacillus thuringiensis- purified proteins and pollen.

Laboratory tests were conducted to establish the relative toxicity of Bacillus thuringiensis (Bt) toxins and pollen from Bt corn to monarch larvae. Toxins tested included Cry1Ab, Cry1Ac, Cry9C, and Cry1F. Three methods were used: (i) purified toxins incorporated into artificial diet, (ii) pollen collected from Bt corn hybrids applied directly to milkweed leaf discs, and (iii) Bt pollen contaminated with corn tassel material applied directly to milkweed leaf discs. Bioassays of purified Bt toxins indicate that Cry9C and Cry1F proteins are relatively nontoxic to monarch first instars, whereas first instars are sensitive to Cry1Ab and Cry1Ac proteins. Older instars were 12 to 23 times less susceptible to Cry1Ab toxin compared with first instars. Pollen bioassays suggest that pollen contaminants, an artifact of pollen processing, can dramatically influence larval survival and weight gains and produce spurious results. The only transgenic corn pollen that consistently affected monarch larvae was from Cry1Ab event 176 hybrids, currently <2% corn planted and for which re-registration has not been applied. Results from the other types of Bt corn suggest that pollen from the Cry1Ab (events Bt11 and Mon810) and Cry1F, and experimental Cry9C hybrids, will have no acute effects on monarch butterfly larvae in field settings.

Induction of hydroxycinnamoyl-tyramine conjugates in pepper by Xanthomonas campestris, a plant defense response activated by hrp gene-dependent and hrp gene-independent mechanisms.

Inoculation of pepper leaves, Capsicum annuum cv. Early Calwonder ECW 10R, with strains of Xanthomonas campestris led to an accumulation of the phenolic conjugates feruloyltyramine (FT) and p-coumaroyltyramine (CT) 24 h postinoculation in nonhost- and gene-for-gene-determined incompatible interactions with X. campestris pv. campestris and X. campestris pv. vesicatoria, respectively. In contrast, neither compound was detected in compatible interactions with X. campestris pv. vesicatoria. The accumulation of FT and CT was preceded by an increase in the extractable activity of tyrosine decarboxylase as well as increases in the transcription of genes encoding phenylalanine ammonia-lyase and tyramine hydroxycinnamoyl transferase. No such changes were detected in compatible interactions. Very rapid accumulation of FT and CT occurred (4 h postinoculation) in pepper in response to a X. campestris pv. campestris mutant carrying a deletion of the hrp gene cluster. In contrast, hrp mutants of X. campestris pv. vesicatoria failed to elicit the production of FT and CT. These observations suggest the existence of hrp gene-dependent and -independent activation mechanisms of a defense response involving hydroxycinnamoyltyramines.

Soil phosphorus variability in pastures: implications for sampling and environmental management strategies.

Soil phosphorus (P) is an increasingly important consideration in the development of P-based nutrient management strategies. The objectives of this study were to (i) obtain baseline information on soil P variability in pastures amended with animal waste, (ii) examine if current sampling recommendations related to the number of subsamples adequately reduce uncertainty to acceptable limits, and (iii) examine the implications of uncertainty in soil P estimates on implementing a soil P threshold of 150 mg kg(-1). Grid soil samples were collected from 12 pastures. Soil P was determined using Mehlich 3 extractant and an inductively coupled argon plasma spectrometer. The arithmetic mean of soil P ranged from 7 mg kg(-1) in a pasture never amended with animal manure to 437 mg kg(-1) in a pasture that had been annually treated long term with poultry litter. Variance of soil P generally increased with mean soil P. The mean standard deviation of all pastures was one-third of the 150 mg kg(-1) threshold. This study points out that smaller variances associated with mean soil P values that approach, but do not exceed, the threshold can influence estimates of soil P. In turn, management decisions could inappropriately change. When a uniform acceptance criteria (within 15 mg kg(-1)) with respect to measured means was used, the required minimum number of subsamples increased with measured standard deviation. The results of this study imply that following soil-sampling recommendations is critical to obtaining trustworthy measures of central tendency, especially in pastures approaching but not exceeding the 150 mg kg(-1) threshold.

Projection structure of a plant vacuole membrane aquaporin by electron cryo-crystallography.

The water channel protein alpha-TIP is a member of the major intrinsic protein (MIP) membrane channel family. This aquaporin is found abundantly in vacuolar membranes of cotyledons (seed storage organs) and is synthesized during seed maturation. The water channel activity of alpha-TIP can be regulated by phosphorylation, and the protein may function in seed desiccation, cytoplasmic osmoregulation, and/or seed rehydration. Alpha-TIP was purified from seed meal of the common bean (Phaseolus vulgaris) by membrane fractionation, solubilization in diheptanoylphosphocholine and anion-exchange chromatography. Upon detergent removal and reconstitution into lipid bilayers, alpha-TIP crystallized as helical tubes. Electron cryo-crystallography of flattened tubes demonstrated that the crystals exhibit plane group p2 symmetry and c222 pseudosymmetry. Since the 2D crystals with p2 symmetry are derived from helical tubes, we infer that the unit of crystallization on the helical lattice is a dimer of tetramers. A projection density map at a resolution of 7.7 A revealed that alpha-TIP assembles as a 60 A x 60 A square tetramer. Each subunit is formed by a heart-shaped ring comprised of density peaks which we interpret as alpha-helices. The similarity of this structure to mammalian plasma membrane MIP-family proteins suggests that the molecular design of functionally analogous and genetically homologous aquaporins is maintained between the plant and animal kingdoms.

Combination of calcium channel blockers and beta-blockers for patients with exercise-induced angina pectoris: beneficial effect of calcium channel blockers largely determined by their effect on heart rate.

The combination of calcium channel blockers and beta-blockers is more effective for the treatment of exercise-induced angina pectoris than beta-blocker monotherapy. As ischemia in exercise-induced angina is essentially preceded by an increase in heart rate, calcium channel blockers with a negative chronotropic property may perform better for this purpose than nonchronotropic compounds. A 335-patient, 10-week, double-blind, parallel-group comparison of amlodipine 5 mg and 10 mg, diltiazem 200 mg and 300 mg, and mibefradil 50 mg and 100 mg treatment added to baseline beta-blocker treatment was performed. Exercise testing (ETT) was performed by bicycle ergometry. All of the calcium channels blockers significantly delayed the onset of 1 mm ST-segment depression on ETT (p < 0.001 for any treatment vs. baseline). In addition, mibefradil, in both low- and high-dose treatments, produced the largest delays (low dose: different from diltiazem and amlodipine by 24.1 and 29.8 seconds, respectively, p < 0.003 and < 0.001; high dose: different from diltiazem and amlodipine by 33.7 and 37.0 seconds, respectively, p < 0.001 and < 0.001). A stepwise logistic regression analysis revealed that this beneficial effect of calcium channel blockers was largely dependent on their effect on heart rate. Serious symptoms of dizziness likewise occurred significantly more frequently on mibefradil (p < 0.05 vs. diltiazem) and urged no fewer than 19 patients on mibefradil to withdraw from the trial. The authors conclude that calcium channel blockers with a negative chronotropic property provide a better delay of ischemia in patients with exercise-induced angina, but the concomitant risk of intolerable dizziness may reduce this benefit.

Combination of calcium channel blockers and beta blockers for patients with exercise-induced angina pectoris: a double-blind parallel-group comparison of different classes of calcium channel blockers. The Netherlands Working Group on Cardiovascular Research (WCN).

The combination of calcium channel blockers and beta blockers is more effective for the treatment of exercise-induced angina pectoris than beta blocker monotherapy. Since ischemia in exercise-induced angina is essentially preceded by an increase in heart rate, calcium channel blockers with negative chronotropic property may perform better for this purpose than nonchronotropic compounds. A 335-patient, 10-week, double-blind, parallel-group comparison of amlodipine 5 and 10 mg, diltiazem XR 200 and 300 mg, and mibefradil 50 and 100 mg treatment added to baseline beta blocker treatment was performed. Exercise testing (ETT) was performed by bicycle ergometry. Although none of the calcium channel blockers improved duration of exercise or amount of workload, all of them significantly delayed onset of 1 mm ST segment depression on ETT (p<0.001 for any treatment versus baseline). In addition, mibefradil, both low- and high-dose treatment, produced the largest delays (low dose: different from diltiazem and amlodipine by 24.1 and 29.8 s, p<0.003 and <0.001, respectively; high dose: different from diltiazem and amlodipine by 33.7 and 37.0 s, p<0.001 and <0.001, respectively). These effects were linearly correlated to the amount of rate pressure product (RPP) reduction. Serious symptoms of dizziness likewise occurred significantly more frequently with mibefradil (p<0.05) and led 19 patients taking mibefradil to withdraw from the trial. The authors conclude that calcium channel blockers with negative chronotropic property provide better delay of ischemia in patients with exercise-induced angina but that the concomitant risk of intolerable dizziness largely reduces this benefit.

Combination of calcium channel blockers and beta-adrenoceptor blockers for patients with exercise-induced angina pectoris: a double-blind parallel-group comparison of different classes of calcium channel blockers. Netherlands Working Group on Cardiovascular Research (WCN).

AIMS: The combination of calcium channel blockers and beta-adrenoceptor blockers is more effective for the treatment of exercise-induced angina pectoris than beta-adrenoceptor blocker monotherapy. As ischaemia in exercise-induced angina is preceded by increase in heart rate, calcium channel blockers with negative chronotropic properties may perform better for this purpose than nonchronotropic compounds. METHODS: A 335 patient double-blind parallel-group study comparing 14 day treatment with amlodipine 5 and 10 mg, with diltiazem 200 and 300 mg, and mibefradil 50 and 100 mg added to baseline beta-adrenoceptor blocker treatment was performed. Exercise testing (ETT) was performed by bicycle ergometry. RESULTS: Although none of the calcium channel blockers improved duration of exercise or amount of workload, all significantly delayed onset of 1 mm ST-segment depression on ETT (P<0.001 for any treatment vs baseline). In addition, mibefradil, both low and high dose treatment, produced the longest delays (low dose: different from diltiazem and amlodipine by 24.1 and 29.8 s, respectively, P<0. 003 and <0.001; high dose: different from diltiazem and amlodipine by 33.7 and 37.0 s, respectively, P<0.001 and <0.001). These effects were linearly correlated with the reduction in rate pressure product (RPP). Serious symptoms of dizziness occurred significantly more frequently on mibefradil (P<0.05), and 19 patients on mibefradil withdrew from trial. CONCLUSIONS: Calcium channel blockers with negative chronotropic properties provide greater delay of ischaemia in patients with exercise-induced angina, but the concomitant risk of intolerable dizziness attenuates this benefit.

The insulinotropic potency of fatty acids is influenced profoundly by their chain length and degree of saturation.

Lowering of the elevated plasma FFA concentration in 18- 24-h fasted rats with nicotinic acid (NA) caused complete ablation of subsequent glucose-stimulated insulin secretion (GSIS). Although the effect of NA was reversed when the fasting level of total FFA was maintained by coinfusion of soybean oil or lard oil (plus heparin), the more saturated animal fat proved to be far more potent in enhancing GSIS. We therefore examined the influence of individual fatty acids on insulin secretion in the perfused rat pancreas. When present in the perfusion fluid at 0.5 mM (in the context of 1% albumin), the fold stimulation of insulin release from the fasted pancreas in response to 12.5 mM glucose was as follows: octanoate (C8:0), 3.4; linoleate (C18:2 cis/cis), 5.3; oleate (C18:1 cis), 9.4; palmitate (C16:0), 16. 2; and stearate (C18:0), 21.0. The equivalent value for palmitoleate (C16:1 cis) was 3.1. A cis--> trans switch of the double bond in the C16:1 and C18:1 fatty acids had only a modest, if any, impact on their potency. A similar profile emerged with regard to basal insulin secretion (3 mM glucose). When a subset of these fatty acids was tested in pancreases from fed animals, the same rank order of effectiveness at both basal and stimulatory levels of glucose was seen. The findings reaffirm the essentiality of an elevated plasma FFA concentration for GSIS in the fasted rat. They also show, however, that the insulinotropic effect of individual fatty acids spans a remarkably broad range, increasing and decreasing dramatically with chain length and degree of unsaturation, respectively. Thus, for any given level of glucose, insulin secretion will be influenced greatly not only by the combined concentration of all circulating (unbound) FFA, but also by the makeup of this FFA pool. Both factors will likely be important considerations in understanding the complex interplay between the nature of dietary fat and whole body insulin, glucose, and lipid dynamics.

A novel proline-rich glycoprotein associated with the extracellular matrix of vascular bundles of Brassica petioles.

A panel of monoclonal antibodies (MAC204, MAC236, MAC265) which recognise extracellular matrix glycoproteins implicated in plant-microbe interactions has been used to study glycoprotein antigens in petioles of turnip (Brassica campestris L.). While MAC204 recognised two glycoproteins (gp120 and gp45) with apparent M(r) 120,000 and 45,000 in petiole extracts made with 2-amino-2-(hydroxymethyl)-1,3-propanediol (Tris) buffer containing sodium dodecyl sulfate, MAC236 recognised gp120 but not gp45, and MAC265 gave no or only weak reactivity. Tissue dissection studies established that gp120 was predominantly associated with the vascular bundle whereas gp45 was largely associated with the pith. This was consistent with results from tissue prints probed with MAC204 and MAC236 which also suggested a vascular localisation for gp120. Immunoelectronmicroscopy showed that MAC204 and MAC236 both labelled three-way junctions between cells of the phloem and sclerid fibres. Both gp120 and gp45 were shown to carry epitopes in common with known hydroxyproline-rich glycoproteins. Unlike gp45, gp120 could be extracted from petioles with Tris buffer alone and then isolated from this extract by trichloroacetic acid treatment (which left gp120 soluble), followed by size-exclusion and ion-exchange chromatography. Amino acid analysis revealed gp120 to be a novel glycoprotein, particularly rich in proline, lysine, valine and threonine but relatively poor in hydroxyproline. The most abundant sugars were arabinose and galactose. The potential role of this very basic cell surface glycoprotein in plant defence against microbes is discussed.

Searching for the biological pathways between stress and health.

Population-based, person-specific health surveys, with concomitant biological measures, should provide important information about the processes by which socioeconomic and psychosocial factors embed themselves in human health. Questionnaire responses allow for assessment of the perceived psychosocial environment, but biological measurements will measure the status of the psychoneuroimmunology/ psychoneuroendocrinology (PNI/PNE) pathways and may allow us to identify people who have "adapted" to their stress because of experience, expectations, stoicism, etc. This review sets criteria to evaluate potential physiological markers of chronic stress. Because population health surveys involve a massive number of samples, special consideration must be given to the laboratory analysis method and transportation time of the markers chosen. We reviewed five areas: glycosylated proteins, the immune system, hemostasis peripheral benzodiazepine receptors, and the waist-hip ratio.

Effect of hormone replacement therapy on bone mass in rheumatoid arthritis patients treated with and without steroids.

OBJECTIVE: To assess the effect of hormone replacement therapy (HRT) on bone mass in rheumatoid arthritis (RA) patients treated with and those not treated with steroids. METHODS: Two hundred postmenopausal women with RA (ages 45-65 years) were randomly allocated to receive transdermal estradiol (hormone replacement therapy; HRT) (50 micrograms daily) or calcium supplementation (400 mg daily) for 2 years. Forty-two of the patients (21%) were taking corticosteroids. Bone mineral density of the lumbar spine (BMDLS) and of the proximal femur (BMDF) was measured at study entry and at 12 months and 24 months. RESULTS: In the HRT group overall, mean BMDLS had changed by +2.22% (95% confidence interval [95% CI] +0.72, +3.72) and mean BMDF by -0.41% (95% CI -1.89, +1.07) after 24 months. In the calcium group, mean BMDLS changed by -1.19% (95% CI -2.29, -0.09) and mean BMDF by -0.56% (95% CI -2.60, +1.48). Differences between treatment groups were significant for the spine only (P < 0.001). In the 21 HRT-treated patients taking steroids, BMDLS increased by 3.75% (95% CI +0.72, +6.78) and BMDF by 1.62% (95% CI -1.27, +4.51). CONCLUSION: This study shows that HRT increases spinal BMD and maintains femoral BMD in postmenopausal RA. HRT is also an effective agent in preserving bone mass in patients taking low-dose corticosteroids.

Preoperative autologous donation: surgery clinic staff knowledge/attitudes. Preoperative Autologous Blood Donation Study Group.

Preoperative autologous blood donation (PABD) is both under- and overused. Although the decision to order PABD lies with the surgeon, it is quite likely that other surgery clinic personnel influence patient acceptance and enrollment into PABD programs. Accordingly, we measured knowledge, attitudes, and the referral practice of clinic personnel pertaining to PABD. We administered a questionnaire to 102 nurses and 33 clerks working in surgery clinics at three university medical centers--one center in an area with a high incidence of AIDS and two centers in areas of low incidence of AIDS. Knowledge of PABD was poor when assessed by six questions. Only 6% each of nurses and clerks answered all questions correctly; 55% of nurses and 54% clerks missed three or more of the six questions. Surprisingly, no differences (P > .05) in knowledge deficits were noted when personnel from high and low AIDS areas were compared--indicating an overall need for education about PABD. In general, attitudes about PABD were positive, as most respondents (63%) gave favorable answers. Clinic personnel from the high AIDS area had even more favorable attitudes (P = .02). Because of these favorable attitudes, it seems likely that educational programs dealing with PABD would be readily accepted by clinic personnel. Greater knowledge should enhance the effectiveness of clinic staff in identifying, counseling, and referring eligible patients for this service.

Glucose regulation of transforming growth factor-alpha expression is mediated by products of the hexosamine biosynthesis pathway.

We have recently shown that glucose and glucosamine regulate the transcription of transforming growth factor-alpha (TGF alpha) in rat aortic smooth muscle (RASM) cells. Based on the increased potency of glucosamine compared to glucose, we hypothesized that stimulation of TGF alpha transcription by glucose is mediated through the hexosamine biosynthesis pathway. The yeast cDNA for the rate-limiting enzyme of this pathway, glutamine:fructose-6-phosphate amidotransferase (GFA), was therefore expressed in RASM cells. GFA-transfected cells showed an increase in GFA activity, exhibiting a 2.2-fold increase in the synthesis of glucosamine-6-phosphate, the first product of the hexosamine biosynthetic pathway. To test the effect of GFA overexpression on TGF alpha transcriptional activity, cells were transiently cotransfected with GFA along with a reporter plasmid containing the firefly luciferase gene under control of the TGF alpha promoter. GFA-transfected cells exhibited a glucose-dependent 2-fold increase in TGF alpha activity compared to control cells. Maximal stimulation of TGF alpha-luciferase activity by glucosamine, however, was equivalent in GFA-and control-transfected cells, confirming that the stimulation observed by both agents operated through the same pathway. This increase in TGF alpha activity was inhibited (85% at 0.5 mM glucose and 69% at 30 mM glucose) by the glutamine analog and inhibitor of GFA, 6-diazo-5-oxonorleucine (10 microM). Control studies confirmed that the increased TGF alpha-luciferase activity in the GFA-expressing cells was not an artifact of altered growth, survival, or transfection efficiency.(ABSTRACT TRUNCATED AT 250 WORDS)

The use of role-play in teaching medical students obstetrics and gynaecology.

There is a great need to review and critically assess medical education. Role-play has seen increasing use as an educational tool. We investigated its role in a 'conventional speciality', Obstetrics and Gynaecology. This is a part of the medical curriculum where communication skills are particularly important, but difficult to learn in practice. Twenty-one medical students took part in three role-play case studies. An innovation we implemented was the use of 'time outs' which could be called at any time through a session. After the exercise students were required to complete a questionnaire designed to probe their attitudes towards the experience. The results indicate that this technique can be successfully used in teaching a conventional speciality. Unlike some previous studies we also found this to be a satisfactory tool in teaching the factual part of the course. We found the 'time out' innovation to be an important aid. We argue that there is an important niche for role-play in medical education.

Surgeons' knowledge, attitude, and use of preoperative autologous blood donation.

Before a comprehensive educational program on preoperative autologous blood donation was begun, 118 surgeons from three different areas of the country were tested to assess their baseline knowledge and attitude about this practice. Test results were correlated with the percentage of eligible patients that the surgeons actually referred for preoperative donation during a period of observation. The purpose of this preliminary effort was to identify areas in the educational program that required emphasis. Overall, the surgeons' attitude toward preoperative donation was quite favorable, but their depth of knowledge varied. Misunderstandings may have led to diminished use of this service (eg, about 50% didn't realize that many patients with medical conditions or low hematocrits are permitted to donate). However, it is not clear that simply bolstering surgeons' knowledge will increase their appropriate use of preoperative donation. When all 118 surgeons were studied, their knowledge and attitude were unrelated to the percentage of eligible patients referred. However, when 44 surgeons who managed the largest number of eligible patients were analyzed separately, their use of preoperative donation was directly correlated with their knowledge and attitude. The local awareness of AIDS also significantly influenced the use of this service. It is proposed that knowledge of preoperative donation may be important for inducing surgeons to begin referring patients for this service. Once a pattern of successful participation is established, referral seems to increase with the acquisition of working knowledge.

Group therapies for rheumatoid arthritis. A controlled study of two approaches.

An important unanswered question about rheumatoid arthritis (RA) is how the patient's psychological or emotional state relates to disease activity and functional status. No controlled studies of psychotherapeutic interventions in RA have been reported. To test the hypothesis that a psychosocial intervention would lead to improvement in functional status or disease activity, 57 RA patients were randomly assigned to 1 of 3 groups, which received: 1) conventional group psychotherapy; 2) group assertion/relaxation training; or 3) no treatment (control group). Patient and physician questionnaires collected at baseline, immediately after the interventions, and 12 months after baseline provided outcome data on functional status, social and psychological adaptation, psychological symptoms, and disease activity. There were few outcome measures for which either treatment resulted in significantly higher scores than were seen in controls, though more improvement did occur among patients who received conventional group psychotherapy.