Mammographic image quality in relation to positioning of the breast: A multicentre international evaluation of the assessment systems currently used, to provide an evidence base for establishing a standardised method of assessment.

INTRODUCTION: Optimum mammography positioning technique is necessary to maximise cancer detection. Current criteria for mammography appraisal lack reliability and validity with a need to develop a more objective system. We aimed to establish current international practice in assessing image quality (IQ), of screening mammograms then develop and validate a reproducible assessment tool. METHODS: A questionnaire sent to centres in countries undertaking population screening identified practice, participants for an expert panel (EP) of radiologists/radiographers and a testing panel (TP) of radiographers. The EP developed category criteria and descriptors using a modified Delphi process to agree definitions. The EP scored 12 screening mammograms to test agreement then a main set of 178 cases. Weighted scores were derived for each descriptor enabling calculation of numerical parameters for each new category. The TP then scored the main set. Statistical analysis included ANOVA, t-tests and Kendall's coefficient. RESULTS: 11 centres in 8 countries responded forming an EP of 7 members and TP of 44 members. The EP showed moderate agreement when the scoring the mini test set W = 0.50 p < 0.001 and the main set W = 0.55 p < 0.001, 'posterior nipple line' being the most difficult descriptor. The weighted total scores differentiated the 4 new categories Perfect, Good, Adequate and Inadequate (p < 0.001). CONCLUSION: We have developed an assessment tool by Delphi consensus and weighted consensus criteria. We have successfully tabulated a range of numerical scores for each new category providing the first validated and reproducible mammography IQ scoring system.

Assessing reader performance in radiology, an imperfect science: lessons from breast screening.

The purpose of this article is to review the limitations associated with current methods of assessing reader accuracy in mammography screening programmes. Clinical audit is commonly used as a quality-assurance tool to monitor the performance of screen readers; however, a number of the metrics employed, such as recall rate as a surrogate for specificity, do not always accurately measure the intended clinical feature. Alternatively, standardized screening test sets, which benefit from ease of application, immediacy of results, and quicker assessment of quality improvement plans, suffer from experimental confounders, thus questioning the relevance of these laboratory-type screening test sets to clinical performance. Four key factors that impact on the external validity of screening test sets were identified: the nature and extent of scrutiny of one's action, the artificiality of the environment, the over-simplification of responses, and prevalence of abnormality. The impact of these factors on radiological and other contexts is discussed, and although it is important to acknowledge the benefit of standardized screening test sets, issues relating to the relevance of test sets to clinical activities remain. The degree of correlation between performance based on real-life clinical audit and performances at screen read test sets must be better understood and specific causal agents for any lack of correlation identified.

Rheological behaviour of polyoxometalate-doped lyotropic lamellar phases.

We study the influence of nanoparticle doping on the lyotropic liquid crystalline phase of the industrial surfactant Brij®30 (C12E4) and water, doped with spherical polyoxometalate nanoparticles smaller than the characteristic dimensions of the host lamellar phase. We present viscometry and in situ rheology coupled with small-angle X-ray scattering data that show that, with increasing doping concentration, the nanoparticles act to decrease the shear viscosity of the lamellar phase, and that a shear-induced transition to a multilamellar vesicle "onion" phase is pushed to higher shear rates, and in some cases completely suppressed. X-ray data reveal that the nanoparticles remain encapsulated within the membranes of the vesicles, thus indicating a viable method for the fabrication of nanoparticle incorporating organic vesicles.

Reader practice in mammography screen reporting in Australia.

Reader variability is a problem in mammography image reporting and compromises the efficacy of screening programmes. The purpose of this exploratory study was to survey reader practice in reporting screening mammograms in Australia to identify aspects of practice that warrant further investigation. Mammography reporting practice and influences on concentration and attention were investigated by using an original questionnaire distributed to screen readers in Australia. A response rate of 71% (83 out of 117) was achieved. Demographic data indicated that the majority of readers were over 46 years of age (73%), have been reporting on screening mammograms for over 10 years (61%), take less than 1 min to report upon a screening mammogram examination (66%), report up to 200 examinations in a single session (83%) and take up to 2 h to report one session (61%). A majority report on more than 5000 examinations annually (66%); 93% of participants regard their search strategy as systematic, 87% agreed that their concentration can vary throughout a session, 64% agreed that the relatively low number of positives can lead to lapses in concentration and attention and almost all (94%) participants agreed that methods to maximise concentration should be explored. Participants identified a range of influences on concentration within their working environment including volume of images reported in one session, image types and aspects of the physical environment. This study has provided important evidence of the need to investigate adverse influences on concentration during mammography screen reporting.

Amygdala-dependent and amygdala-independent pathways for contextual fear conditioning.

The basolateral amygdala (BLA), consisting of the lateral and basal nuclei, is considered to be essential for fear learning. Using a temporary inactivation technique, we found that rats could acquire a context-specific long-term fear memory without the BLA but only if intensive overtraining was used. BLA-inactivated rats' learning curves were characterized by slow learning that eventually achieved the same asymptotic performance as rats with the BLA functional. BLA inactivation abolished expression of overtrained fear when rats were overtrained with a functional BLA. However, BLA-inactivation had no effect on the expression of fear in rats that learned while the BLA was inactivated. These data suggest that there are primary and alternate pathways capable of mediating fear. Normally, learning is dominated by the more efficient primary pathway, which prevents learning in the alternate pathway. However, alternate pathways compensate when the dominant pathway is compromised.

A novel long chain polyunsaturated fatty acid, beta-Oxa 21:3n-3, inhibits T lymphocyte proliferation, cytokine production, delayed-type hypersensitivity, and carrageenan-induced paw reaction and selectively targets intracellular signals.

A novel polyunsaturated fatty acid (PUFA), beta-oxa 21:3n-3, containing an oxygen atom in the beta position, was chemically synthesized, and found to have more selective biological activity than the n-3 PUFA, docosahexaenoic acid (22:6n-3) on cells of the immune system. Although beta-oxa 21:3n-3 was very poor compared with 22:6n-3 at stimulating oxygen radical production in neutrophils, it was more effective at inhibiting human T lymphocyte proliferation (IC(50) of 1.9 vs 5.2 microM, respectively). beta-Oxa 21:3n-3 also inhibited the production of TNF-beta, IFN-gamma, and IL-2 by purified human T lymphocytes stimulated with PHA plus PMA, anti-CD3 plus anti-CD28 mAbs, or PMA plus A23187. Metabolism of beta-oxa 21:3n-3 via the cyclooxygenase and lipoxygenase pathways was not required for its inhibitory effects. Consistent with its ability to suppress T lymphocyte function, beta-oxa 21:3n-3 significantly inhibited the delayed-type hypersensitivity response and carrageenan-induced paw edema in mice. In T lymphocytes, beta-oxa 21:3n-3 inhibited the agonist-stimulated translocation of protein kinase C-betaI and -epsilon, but not -alpha, -betaII, or -theta to a particulate fraction, and also inhibited the activation of the extracellular signal-regulated protein kinase, but not c-Jun NH(2)-terminal kinase and p38. In contrast, 22:6n-3 had no effects on these protein kinase C isozymes. The increase in antiinflammatory activity and loss of unwanted bioaction through the generation of a novel synthetic 22:6n-3 analogue provides evidence for a novel strategy in the development of anti-inflammatory agents by chemically engineering PUFA.

Pain, mood disturbance, and quality of life in patients with multiple myeloma.

PURPOSE/OBJECTIVES: To determine the levels of pain intensity and pain interference in patients with multiple myeloma, the relationship between pain and mood disturbance, and factors that influence quality of life (QOL). DESIGN: Descriptive correlational mailed survey. SETTING: A private tertiary institution in the Midwest. SAMPLE: Convenience sample of 346 adult patients with multiple myeloma identified through an institutional database, 206 of whom responded to the surveys. METHODS: Mailed, self-administered questionnaires: Brief Pain Inventory Short Form, Profile of Mood States, QOL Scale (Cancer Patient Version), and a demographic tool. Treatment details were obtained from the database on subjects consenting to participate. MAIN RESEARCH VARIABLES: Pain intensity, pain interference, psychologic functioning, and QOL. FINDINGS: 29% (n = 60) of subjects reported moderate to severe pain intensity. Significant associations were found between pain intensity and mood disturbance scores. As pain interference increased, so did levels of mood disturbance. A joint predictive model explained 74.6% of the variability in total QOL scores. CONCLUSIONS: Cancer pain remains undertreated, and patients with myeloma are no exception. Pain and mood disturbance scores were significant predictors of QOL in this group of patients. Subjects with multiple myeloma reported higher levels of mood disturbance than patients with cancer from other studies. IMPLICATIONS FOR NURSING PRACTICE: The oncology nurse is in a key position to facilitate ongoing, adequate pain and psychosocial assessment of patients with myeloma. Further study is needed to determine if control of pain and mood disturbance factors has a positive effect on the various domains of QOL.

A detailed audit of reimbursement for abdominal CT in an academic practice.

RATIONALE AND OBJECTIVES: Declining fee schedules, decreasing operating margins, and increasingly stringent compliance regulations create a need for intense scrutiny and optimization of a radiology organization's billing and collection procedures. The authors' goal was to analyze the effectiveness of departmental professional billing procedures, identify controllable factors, and intervene when they could be improved. MATERIALS AND METHODS: A detailed audit of professional claims and payments was performed for all patients who underwent abdominal-pelvic computed tomography (CT) during July 1999 (n = 717). The adequacy of indication for the CT examination as given by the referring physician and modified by the radiology staff, the time required for claim generation, and the status of reimbursement within 120 days were assessed by an interdisciplinary team. After an intervention was performed to improve adequacy of the available clinical indication, the audit was repeated in December 1999 (n = 710). RESULTS: Despite a significant (P < .05) improvement in wording of clinical indications for billing purposes between July (68%) and December (85%), there was no significant change in reimbursement against gross charges. The vast majority of claims (97% in July, 99% in December) were generated in less than 30 days. At 120 days after the date of service, payments had been received that amounted to only 66% and 54% of discounted professional fees for July and December, respectively. For examinations performed in December, payment was delayed beyond contracted time periods in 138 cases (19%). CONCLUSION: Optimum billing and collection for imaging studies is an increasingly complex task. Even when substantial efforts are devoted to eliciting the proper indication for the study, reimbursement remains low primarily because of payer delays.

Oxidation of oxa and thia fatty acids and related compounds catalysed by 5- and 15-lipoxygenase.

The modified fatty acids, (Z,Z,Z)-(octadeca-6,9,12-trienyloxy)acetic acid, (Z,Z,Z)-(octadeca-9,12,15-trienyloxy)acetic acid, (all-Z)-(eicosa-5,8,11,14-tetraenyloxy)acetic acid, (all-Z)-(eicosa-5,8,11,14-tetraenylthio)acetic acid, 3-[(all-Z)-(eicosa-5,8,11,14-tetraenylthio)]propionic acid, (all-Z)-(eicosa-5,8,11,14-tetraenylthio)succinic acid, N-[(all-Z)-(eicosa-5,8,11,14-tetraenoyl)]glycine and N-[(all-Z)-(eicosa-5,8,11,14-tetraenoyl)]aspartic acid, all react with soybean 15-lipoxygenase. The products were treated with triphenylphosphine to give alcohols, which were isolated using HPLC. Analysis of the alcohols using negative ion tandem electrospray mass spectrometry, and by comparison with compounds obtained by autoxidation of arachidonic acid, shows that each enzyme-catalysed oxidation occurs at the omega-6 position of the substrate. In a similar fashion, it has been found that (Z,Z,Z)-(octadeca-6,9,12-trienyloxy)acetic acid, (Z,Z,Z)-(octadeca-9,12,15-trienyloxy)acetic acid, (all-Z)-(eicosa-5,8,11,14-tetraenylthio)acetic acid and 3-[(all-Z)-(eicosa-5,8,11,14-tetraenylthio)]propionic acid each undergoes regioselective oxidation at the carboxyl end of the polyene moiety on treatment with potato 5-lipoxygenase. Neither (all-Z)-(eicosa-5,8,11,14-tetraenylthio)succinic acid nor N-[(all-Z)-(eicosa-5,8,11,14-tetraenoyl)]aspartic acid reacts in the presence of this enzyme, while N-[(all-Z)-(eicosa-5,8,11,14-tetraenoyl)]glycine affords the C11' oxidation product. The alcohol derived from (Z,Z,Z)-(octadeca-6,9,12-trienyloxy)acetic acid using the 15-lipoxygenase reacts at the C6' position with the 5-lipoxygenase.

Comparison of total body potassium with other techniques for measuring lean body mass in men and women with AIDS wasting.

BACKGROUND: Lean body mass is an important predictor of survival and functional status in patients with AIDS wasting. The bias between different techniques for assessing body composition in AIDS wasting is not known. DESIGN: We compared total body potassium (TBK) with fat-free mass (FFM) determined by dual-energy X-ray absorptiometry (DXA), bioelectrical impedance analysis (BIA), and skinfold-thickness measurement (SKF) in 132 patients (63 men, 69 women) with AIDS wasting (weight < 90% of ideal body weight, or weight loss > 10% of original, or both). None of the subjects exhibited clinical lipodystrophy. Comparisons were made by using different BIA equations. RESULTS: Lean body mass determined by DXA was highly correlated with TBK in men (r = 0.79, P: < 0.0001) and women (r = 0.84, P: < 0.0001). FFM(BIA) and FFM(DXA) were significantly different (P: < 0.01 in men and P: < 0.0001 in women). The difference between FFM(DXA) and FFM(BIA) was significantly greater with greater weight and body fat, particularly in HIV-infected women (r = -0.39, P: = 0.001 for weight; r = -0.60, P: < 0.0001 for fat). The comparability of FFM and fat mass determined by DXA and BIA was dependent on the specific BIA equation used. Among men, no single BIA equation was more highly predictive of fat mass and FFM in comparison with DXA. CONCLUSIONS: The differences between DXA, BIA, and SKF in the determination of fat mass and FFM are significant in patients with AIDS wasting. BIA overestimates FFM compared with DXA in those with greater body fat. Standard BIA equations may not accurately estimate FFM and fat mass in men and women with AIDS wasting.

Metabolism of trideuterated iso-lignoceric acid in rats in vivo and in human fibroblasts in culture.

Saturated very long chain fatty acids (fatty acids with greater than 22 carbon atoms; VLCFA) accumulate in peroxisomal disorders, but there is little information on their turnover in patients. To determine the suitability of using stable isotope-labeled VLCFA in patients with these disorders, the metabolism of 22-methyl[23,23,23-2H3]tricosanoic (iso-lignoceric) acid was studied in rats in vivo and in human skin fibroblasts in culture. The deuterated iso-VLCFA was degraded to the corresponding 16- and 18-carbon iso-fatty acids by rats in vivo and by normal human skin fibroblasts in culture, but there was little or no degradation in peroxisome-deficient (Zellweger's syndrome) fibroblasts, indicating that its oxidation was peroxisomal. Neither the 14-, 20-, and 22-carbon iso-fatty acids nor the corresponding odd-chain metabolites could be detected. In the rat, the organ containing most of the iso-lignoceric acid, and its breakdown products, was the liver, whereas negligible amounts were detected in the brain, suggesting that little of the fatty acid crossed the blood-brain barrier. Our data indicate that VLCFA labeled with deuterium at the omega-position of the carbon chain are suitable derivatives for the in vivo investigation of patients with defects in peroxisomal beta-oxidation because they are metabolized by the same pathways as the corresponding n-VLCFA. Moreover, as iso-VLCFA and their beta-oxidation products are readily separated from the corresponding n-fatty acids by normal chromatographic procedures, the turnover of VLCFA can be more precisely measured.

Investigation of thyroid dose due to mammography.

The radiation dose to the skin overlying the thyroid was measured for 91 women undergoing routine mammographic screening. Measurement was made over 6 days using thermoluminescent dosimeter (TLD) detectors taped appropriately to the neck. An average skin dose of 0.39 +/- 0.22 mGy per mammographic examination was measured with measurements ranging from background levels to 1.15 mGy. The average dose was significantly correlated to the milliampere-seconds for a total procedure. The mediolateral-oblique view was found to give a 2.4-fold greater skin dose at the thyroid than the craniocaudal view. After considering depth dose data from the literature it was conservatively estimated that the dose to the thyroid gland might be 10% of the skin dose overlying the thyroid. This corresponds to an average thyroid dose during mammography of approximately 0.04 mGy which is considered insignificant compared with the average breast dose (4 mGy) and in light of the relevant available literature on the risk to the thyroid.

X-linked adrenoleukodystrophy: the Australasian experience.

Our objective was to review the Australasian experience of X-linked adrenoleukodystrophy (ALD), to compare the spectrum of disease seen in Australasia with previously published data from elsewhere, and to assess the reliability of carrier testing. Study design was a retrospective review of records collected over a 15-year period, the setting was an international referral laboratory for the study of metabolic disease, and the subjects were all known cases of ALD diagnosed in Australia and New Zealand between 1981 and 1996 and their families. We estimate that the combined incidence of ALD and its variants in Australasia is at least 1.6 per 100,000. Of 95 affected males, 51 had cerebral adrenoleukodystrophy, 24 had adrenomyeloneuropathy, 15 had Addison's disease only, and 5 remained asymptomatic when last examined. However, the distribution of phenotypes among newly diagnosed patients has changed substantially over the last 15 years, with cerebral forms of the disease forming a decreasing proportion of new diagnoses. The measurement of plasma very long chain fatty acids (VLCFAs) alone detects 93% of women who can be proven to be carriers. The addition of genetic linkage studies or assay of VLCFAs in cultured fibroblasts improved this detection rate to the point that there were no obligate carriers who could not be detected using a combination of two or more techniques.

Enhancement of neutrophil-mediated killing of Plasmodium falciparum asexual blood forms by fatty acids: importance of fatty acid structure.

Effects of fatty acids on human neutrophil-mediated killing of Plasmodium falciparum asexual blood forms were investigated by using a quantitative radiometric assay. The results showed that the antiparasitic activity of neutrophils can be greatly increased (>threefold) by short-term treatment with fatty acids with 20 to 24 carbon atoms and at least three double bonds. In particular, the n-3 polyenoic fatty acids, eicosapentaenoic and docosahexaenoic acids, and the n-6 fatty acid, arachidonic acid, significantly enhanced neutrophil antiparasitic activity. This effect was >1.5-fold higher than that induced by an optical concentration of the known agonist cytokine tumor necrosis factor alpha (TNF-alpha). At suboptimal concentrations, the combination of arachidonic acid and TNF-alpha caused a synergistic increase in neutrophil-mediated parasite killing. The fatty acid-induced effect was independent of the availability of serum opsonins but dependent on the structure of the fatty acids. The length of the carbon chain, degree of unsaturation, and availability of a free carboxyl group were important determinants of fatty acid activity. The fatty acids which increased neutrophil-mediated killing primed the enhanced superoxide radical generation of neutrophils in response to P. falciparum as detected by chemiluminescence. Scavengers of oxygen radicals significantly reduced the fatty acid-enhanced parasite killing, but cyclooxygenase and lipoxygenase inhibitors had no effect. These findings have identified a new class of immunoenhancers that could be exploited to increase resistance against Plasmodium species.

Compression in mammography and the perception of discomfort.

Breast compression in mammography is an uncomfortable experience for most women. The discomfort experienced has the potential to deter women from attending regular breast screening by mammography. The aim of the present study was to assess factors related to the degree of discomfort experienced by women attending for first-time mammography at the Central and Eastern Sydney BreastScreen Service. Prior to the mammogram, expectations of discomfort, menstrual status, existing breast pain, and other breast problems were recorded on a questionnaire. At the time of the mammogram, breast size and weight were estimated. During the mammogram one of the craniocaudal views of the breast was taken at a slightly lower level of compression and after the procedure the participants were asked if they perceived any difference in discomfort between the normally compressed view and the less compressed view. Radiologists were asked to comment on any differences in image quality between the same two cranio-caudal films. A total of 200 women, including non-English-speaking women, participated in the present study. A total of 29% of women reported moderate, considerable or severe discomfort, a much higher level than reported in previous studies. The source of expectations (P = 0.001) had a significant relationship to the expectation of discomfort. Prior expectations (P = 0.01) and breast weight (P = 0.001) were the only factors found to have a significant relationship to the experience of discomfort. The analysis of differences in level of compression and discomfort indicates that the relationship between mammography discomfort and level of compression is complex and not simply the result of the amount of compression applied. However, analysis of the relationship of varying compression and image quality suggests that a slight lowering in the level of compression is unlikely to significantly compromise perceived image quality. Directions for further research are suggested.

N-6 and n-3 polyunsaturated fatty acids stimulate translocation of protein kinase Calpha, -betaI, -betaII and -epsilon and enhance agonist-induced NADPH oxidase in macrophages.

The polyunsaturated fatty acids (PUFA), arachidonic acid (AA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) were poor inducers of oxygen-dependent respiratory activity (chemiluminescence) in human monocytes and macrophages, but markedly enhanced the response to the tripeptide, N-formylmethionyl-leucyl-phenylalanine. The effects of these fatty acids were seen at concentrations of 1 microg/ml. A similar enhancement was seen with PMA, a stimulus that acts on protein kinase C (PKC), or calcium ionophore (A23187), which increases intracellular calcium, suggesting that the effect of the fatty acids was post-surface receptor binding. HL-60 cells, differentiated to macrophage-like cells by culture in the presence of vitamin D3, were similarly affected by the fatty acids. In experiments in which the time of pre-exposure of the monocytes to PUFA was varied, it was found that the priming effect induced by AA, EPA and DHA was maximal at 5 min. The ability of these fatty acids to synergize with other agonists was completely lost if the fatty acids were either methylated or oxidized to the hydro and hydroperoxy derivatives. Saturated fatty acids were inactive. Western blot analysis demonstrated that the PUFA induced the translocation of PKCalpha, -betaI, -betaII and -epsilon isoenzymes to a particulate fraction. The synergistic response between fatty acids and A23187 was completely inhibited by pretreating the cells with a PKC inhibitor, GF-109203X, or by pretreatment of monocytes with PMA for 18 h, to deplete PKC levels. From these investigations it is evident that PUFA prime macrophages, causing increased/synergistic oxidative respiratory burst activity to other stimuli and that this priming is dependent on PKC translocation and activation.

Activation of neutral sphingomyelinase in human neutrophils by polyunsaturated fatty acids.

Although unesterified polyunsaturated fatty acids (PUFA) have been shown to elicit marked changes in neutrophil function, the associated signal transduction processes require clarification. In this study we examined the effect of PUFA on the sphingomyelin (SM)-signalling cycle in human neutrophils. Treatment of neutrophils with eicosatetraenoic acid [arachidonic acid, 20:4(n-6)] caused a decrease in the mass of cellular SM and an increase in the level of ceramide. 20:4(n-6)-stimulated neutral sphingomyelinase (SMase) activity of the leucocytes in a time- and concentration-dependent manner. Other unsaturated fatty acids, docosahexaenoic [22:6(n-3)], eicosapentaenoic [20:5(n-3)], octadecenoic [oleic, 18:1(n-9)] and octadecadienoic [linoleic, 18:2(n-6)] acids also had the capacity to activate neutral SMase; however, certain 20:4(n-6) derivatives ¿20:4(n-6) methyl ester [20:4(n-6)ME], 15-hydroperoxyeicosatetraenoic (15-HPETE) and 15-hydroxyeicosatetraenoic (15-HETE) acids¿, very-long-chain PUFA ¿tetracosatetraenoic [24:4(n-6)] and octacosatetraenoic [28:4(n-6)] acids¿ and saturated fatty acids [octadecanoic (stearic, 18:0) and eicosanoic (arachidic, 20:0) acids] had no significant effect. Activation of neutral SMase by 20:4(n-6) appeared to involve metabolism via 20:4(n-6)CoA (arachidonoyl CoA) and was not dependent on prostaglandin and leukotriene synthesis. All of the fatty acids and derivatives tested failed to activate acidic SMase of neutrophils. Ceramide was found to inhibit 20:4(n-6)-induced superoxide generation by the cells. It is envisaged that the PUFA-induced ceramide production in neutrophils plays a role in the regulation of biological responses.