Symptoms at stroke onset as described by patients: a qualitative study.

BACKGROUND: Stroke is a common and severe disease that requires prompt care. Symptom expressions as one-sided weakness and speech difficulties are common and included in public stroke campaigns. For some patients stroke can present with subtle and less common symptoms, difficult to interpret. The symptom severity assessed by the National Institutes of Health Stroke Scale has decreased, and symptoms at onset may have changed. Therefore, we aimed to investigate how patients describe their symptoms at the onset of a first-time stroke. METHODS: The study used a qualitative descriptive design and conventional content analysis. Data were collected through recorded interviews with 27 patients aged 18 years and older hospitalised with a first-time stroke between October 2018 and April 2020. Data were analysed on a manifest level. RESULTS: Symptoms at stroke onset were presented in two themes: Altered Reality and Discomfort and Changed Body Functions and described in five categories. Various types of symptoms were found. All symptoms were perceived as sudden, persistent, and never experienced before and this appear as a "red thread" in the result. Regardless of symptom expressions, no specific symptom was described as more severe than another. CONCLUSIONS: Stroke symptoms were described with a variety of expressions. Many described complex symptoms not typical of stroke, which can make it difficult to recognise the symptoms as a stroke and delay medical care. Public stroke campaigns should emphasize the importance of seeking medical care at the slightest suspicion of stroke and could be designed to help achieve this.

Interactive effects of drought and edge exposure on old-growth forest understory species.

Context: Both climatic extremes and land-use change constitute severe threats to biodiversity, but their interactive effects remain poorly understood. In forest ecosystems, the effects of climatic extremes can be exacerbated at forest edges. Objectives: We explored the hypothesis that an extreme summer drought reduced the richness and coverage of old-growth forest species, particularly in forest patches with high edge exposure. Methods: Using a high-resolution spatially explicit precipitation dataset, we could detect variability in drought intensity during the summer drought of 2018. We selected 60 old-growth boreal forest patches in central Sweden that differed in their level of drought intensity and amount of edge exposure. The year after the drought, we surveyed red-listed and old-growth forest indicator species of vascular plants, lichens and bryophytes. We assessed if species richness, composition, and coverage were related to drought intensity, edge exposure, and their interaction. Results: Species richness was negatively related to drought intensity in forest patches with a high edge exposure, but not in patches with less edge exposure. Patterns differed among organism groups and were strongest for cyanolichens, epiphytes associated with high-pH bark, and species occurring on convex substrates such as trees and logs. Conclusions: Our results show that the effects of an extreme climatic event on forest species can vary strongly across a landscape. Edge exposed old-growth forest patches are more at risk under extreme climatic events than those in continuous forests. This suggest that maintaining buffer zones around forest patches with high conservation values should be an important conservation measure. Supplementary information: The online version contains supplementary material available at 10.1007/s10980-022-01441-9.

Planning the American Future: Daniel Bell, Future Research, and the Commission on the Year 2000.

This article examines the sociologist Daniel Bell's interest in future research. Future research, to Bell, had as its particular purpose to ensure forms of coordination and steering acceptable to a liberal society. By examining Bell's interest in future research and the activities of the Commission on the Year 2000, the essay proposes that future research played a role in Cold War intellectual history as a particular form of planning for the liberal polity. This idea of planning a liberal society changed decisively, however, between 1965 and 1975.

"It was as if I wasn't there" - Experiences of everyday racism in a Swedish medical school.

The aim of this study was to explore and analyze how cultural/ethnic minority students at a Swedish medical school perceive and make sense of educational experiences they viewed as related to their minority position. We interviewed 18 medical students (10 women, and 8 men), who self-identified as coming from minority backgrounds. Data were collected and analyzed simultaneously, inspired by constructivist grounded theory methodology. The concepts 'everyday racism' and 'racial microaggressions' served as a theoretical framework for understanding how inequities were experienced and understood. Participants described regularly encountering subtle adverse treatment from supervisors, peers, staff, and patients. Lack of support from bystanders was a common dimension of their stories. These experiences marked interviewees' status as 'Other' and made them feel less worthy as medical students. Interviewees struggled to make sense of being downgraded, excluded, and discerned as different, but seldom used terms like being a victim of discrimination or racism. Instead, they found other explanations by individualizing, renaming, and relativizing their experiences. Our results indicate that racialized minority medical students encounter repeated practices that, either intentionally or inadvertently, convey disregard and sometimes contempt based on ideas about racial and/or cultural 'Otherness'. However, most hesitated to name the behaviors and comments experienced as "discriminatory" or "racist", likely because of prevailing ideas about Sweden and, in particular, medical school as exempt from racism, and beliefs that racial discrimination can only be intentional. To counteract this educational climate of exclusion medical school leadership should provide supervisors, students, and staff with theoretical concepts for understanding discrimination and racism, encourage them to engage in critical self-reflection on their roles in racist power relations, and offer training for bystanders to become allies to victims of racism.

Umeå University's proposed "Rural Stream" - An effective alternative to the longitudinal integrated clerkship model for small rural communities?

Background: Umeå University Faculty of Medicine (UUFM), Sweden, has a regionalized medical program in which students spend the final 2½ years of their undergraduate degree in district hospitals. In late 2018, UUFM started a "rural stream" pilot exposing students to smaller rural locations. Methods: The objectives are to deliver the benefits for medical education and rural workforce development that have been observed in longitudinal integrated clerkships (LICs) while maintaining consistency between learning experiences in the main campus, regional campuses, and rural locations. This article compares the UUFM rural stream with those typical of the LICs described in the medical education literature. Comparisons are made in terms of the four key criteria for LIC success, and additional characteristics including peer and interprofessional learning, "'continuity," and curriculum development. Results: The rural stream has elements of length, immersion, position in the degree program, and community engagement that are both similar to, and different from, LICs. Key challenges are to ensure that participating students create close relationships with host medical facilities and communities. The rural stream also has some potential advantages, particularly in relation to team learning. Discussion: Alternatives to the LIC rural stream model as typically described in the literature may be required to allow for immersive medical education to occur in smaller rural communities and to be suitable for medical schools with more traditional approaches to education.

The plant dehydrin Lti30 stabilizes lipid lamellar structures in varying hydration conditions.

A major challenge to plant growth and survival are changes in temperature and diminishing water supply. During acute temperature and water stress, plants often express stress proteins, such as dehydrins, which are intrinsically disordered hydrophilic proteins. In this article, we investigated how the dehydrin Lti30 from Arabidopsis thaliana stabilizes membrane systems that are exposed to large changes in hydration. We also compared the effects of Lti30 on membranes with those of the simple osmolytes urea and trimethylamine N-oxide. Using X-ray diffraction and solid-state NMR, we studied lipid-protein self-assembly at varying hydration levels. We made the following observations: 1) the association of Lti30 with anionic membranes relies on electrostatic attraction, and the protein is located in the bilayer interfacial membrane region; 2) Lti30 can stabilize the lamellar multilayer structure, making it insensitive to variations in water content; 3) in lipid systems with a composition similar to those present in some seeds and plants, dehydrin can prevent the formation of nonlamellar phases upon drying, which may be crucial for maintaining membrane integrity; and 4) Lti30 stabilizes bilayer structures both at high and low water contents, whereas the small osmolyte molecules mainly prevent dehydration-induced transitions. These results corroborate the idea that dehydrins are part of a sensitive and multifaceted regulatory mechanism that protects plant cells against stress.

To select or be selected - gendered experiences in clinical training affect medical students' specialty preferences.

BACKGROUND: The literature investigating female and male medical students' differing career intentions is extensive. However, medical school experiences and their implications for professional identity formation and specialty choice have attracted less attention. In this study we explore the impact of medical school experiences on students' specialty preferences, investigate gender similarities and differences, and discuss how both might be related to gender segregation in specialty preference. METHODS: In a questionnaire, 250 Swedish final-year medical students described experiences that made them interested and uninterested in a specialty. Utilizing a sequential mixed methods design, their responses were analyzed qualitatively to create categories that were compared quantitatively. RESULTS: Similar proportions of women and men became interested in a specialty based on its knowledge area, patient characteristics, and potential for work-life balance. These aspects, however, often became secondary to whether they felt included or excluded in clinical settings. More women than men had been deterred by specialties with excluding, hostile, or sexist workplace climates (W = 44%, M = 16%). In contrast, more men had been discouraged by specialties' knowledge areas (W = 27%, M = 47%). CONCLUSIONS: Male and female undergraduates have similar incentives and concerns regarding their career. However, the prevalence of hostility and sexism in the learning environment discourages especially women from some specialties. To reduce gender segregation in specialty choice, energy should be directed towards counteracting hostile workplace climates that explain apparent stereotypical assumptions about career preferences of men and women.

The Impact of Nonequilibrium Conditions in Lung Surfactant: Structure and Composition Gradients in Multilamellar Films.

The lipid-protein mixture that covers the lung alveoli, lung surfactant, ensures mechanical robustness and controls gas transport during breathing. Lung surfactant is located at an interface between water-rich tissue and humid, but not fully saturated, air. The resulting humidity difference places the lung surfactant film out of thermodynamic equilibrium, which triggers the buildup of a water gradient. Here, we present a millifluidic method to assemble multilamellar interfacial films from vesicular dispersions of a clinical lung surfactant extract used in replacement therapy. Using small-angle X-ray scattering, infrared, Raman, and optical microscopies, we show that the interfacial film consists of several coexisting lamellar phases displaying a substantial variation in water swelling. This complex phase behavior contrasts to observations made under equilibrium conditions. We demonstrate that this disparity stems from additional lipid and protein gradients originating from differences in their transport properties. Supplementing the extract with cholesterol, to levels similar to the endogenous lung surfactant, dispels this complexity. We observed a homogeneous multilayer structure consisting of a single lamellar phase exhibiting negligible variations in swelling in the water gradient. Our results demonstrate the necessity of considering nonequilibrium thermodynamic conditions to study the structure of lung surfactant multilayer films, which is not accessible in bulk or monolayer studies. Our reconstitution methodology also opens avenues for lung surfactant pharmaceuticals and the understanding of composition, structure, and property relationships at biological air-liquid interfaces.

Fabrication and Characterization of Plasmonic Nanopores with Cavities in the Solid Support.

Plasmonic nanostructures are widely used for various sensing applications by monitoring changes in refractive index through optical spectroscopy or as substrates for surface enhanced Raman spectroscopy. However, in most practical situations conventional surface plasmon resonance is preferred for biomolecular interaction analysis because of its high resolution in surface coverage and the simple single-material planar interface. Still, plasmonic nanostructures may find unique sensing applications, for instance when the nanoscale geometry itself is of interest. This calls for new methods to prepare nanoscale particles and cavities with controllable dimensions and curvature. In this work, we present two types of plasmonic nanopores where the solid support underneath a nanohole array has been etched, thereby creating cavities denoted as 'nanowells' or 'nanocaves' depending on the degree of anisotropy (dry or wet etch). The refractometric sensitivity is shown to be enhanced upon removing the solid support because of an increased probing volume and a shift of the asymmetric plasmonic field towards the liquid side of the finite gold film. Furthermore, the structures exhibit different spectral changes upon binding inside the cavities compared to the gold surface, which means that the structures can be used for location-specific detection. Other sensing applications are also suggested.

Nanoplasmonic Sensing at the Carbon-Bio Interface: Study of Protein Adsorption at Graphitic and Hydrogenated Carbon Surfaces.

Various forms of carbon are known to perform well as biomaterials in a variety of applications and an improved understanding of their interactions with biomolecules, cells, and tissues is of interest for improving and tailoring their performance. Nanoplasmonic sensing (NPS) has emerged as a powerful technique for studying the thermodynamics and kinetics of interfacial reactions. In this work, the in situ adsorption of two proteins, bovine serum albumin and fibrinogen, were studied at carbon surfaces with differing chemical and optical properties using nanoplasmonic sensors. The carbon material was deposited as a thin film onto NPS surfaces consisting of 100 nm Au nanodisks with a localized plasmon absorption peak in the visible region. Carbon films were fully characterized by X-ray photoelectron spectroscopy, atomic force microscopy, and spectroscopic ellipsometry. Two types of material were investigated: amorphous carbon (a-C), with high graphitic content and high optical absorptivity, and hydrogenated amorphous carbon (a-C:H), with low graphitic content and high optical transparency. The optical response of the Au/carbon NPS elements was modeled using the finite difference time domain (FDTD) method, yielding simulated analytical sensitivities that compare well with those observed experimentally at the two carbon surfaces. Protein adsorption was investigated on a-C and a-C:H, and the protein layer thicknesses were obtained from FDTD simulations of the expected response, yielding values in the 1.8-3.3 nm range. A comparison of the results at a-C and a-C:H indicates that in both cases fibrinogen layers are thicker than those formed by albumin by up to 80%.

Effect of cholesterol on the molecular structure and transitions in a clinical-grade lung surfactant extract.

The lipid-protein film covering the interface of the lung alveolar in mammals is vital for proper lung function and its deficiency is related to a range of diseases. Here we present a molecular-level characterization of a clinical-grade porcine lung surfactant extract using a multitechnique approach consisting of [Formula: see text]-[Formula: see text] solid-state nuclear magnetic spectroscopy, small- and wide-angle X-ray scattering, and mass spectrometry. The detailed characterization presented for reconstituted membranes of a lung extract demonstrates that the molecular structure of lung surfactant strongly depends on the concentration of cholesterol. If cholesterol makes up about 11% of the total dry weight of lung surfactant, the surfactant extract adopts a single liquid-ordered lamellar phase, [Formula: see text], at physiological temperatures. This [Formula: see text] phase gradually changes into a liquid-disordered lamellar phase, [Formula: see text], when the temperature is increased by a few degrees. In the absence of cholesterol the system segregates into one lamellar gel phase and one [Formula: see text] phase. Remarkably, it was possible to measure a large set of order parameter magnitudes [Formula: see text] from the liquid-disordered and -ordered lamellar phases and assign them to specific C-H bonds of the phospholipids in the biological extract with no use of isotopic labeling. These findings with molecular details on lung surfactant mixtures together with the presented NMR methodology may guide further development of pulmonary surfactant pharmaceuticals that better mimic the physiological self-assembly compositions for treatment of pathological states such as respiratory distress syndrome.

Experiences of the gender climate in clinical training - a focus group study among Swedish medical students.

BACKGROUND: Research shows that medical education is characterized by unequal conditions for women and men, but there is a lack of qualitative studies investigating the social processes that enable and maintain gender inequalities that include both male and female students. In this focus group study, we therefore explored male as well as female medical students' experiences of the gender climate - i.e., how beliefs, values, and norms about gender were communicated - during clinical training and how the students dealt with these experiences. METHODS: Focus group interviews were conducted with 24 medical students (nine men) at Umeå University, Sweden. The interviews were structured around personal experiences in clinical training where the participants perceived that gender had mattered. Data were analysed using qualitative content analysis. RESULTS: The students described gender-stereotyped expectations, discriminatory treatment, compliments, comments, and demeaning jargon. Female students gave more personal and varied examples than the men. The students' ways of handling their experiences were marked by efforts to fit in, for example, by adapting their appearance and partaking in the prevailing jargon. They felt dependent on supervisors and staff, and due to fear of repercussions they kept silent and avoided unpleasant situations and people rather than challenging humiliating jargon or supervisors who were behaving badly. CONCLUSIONS: Everyday communication of gender beliefs combined with students' adaptation to stereotyped expectations and discrimination came across as fundamental features through which unequal conditions for male and female students are reproduced and maintained in the clinic. Because they are in a dependent position, it is often difficult for students to challenge problematic gender attitudes. The main responsibility for improvements, therefore, lies with medical school leadership who need to provide students and supervisors with knowledge about gendered processes, discrimination, and sexism and to organize reflection groups about the gender climate in order to improve students' opportunities to discuss their experiences, and hopefully find ways to protest and actively demand change.

Stratum corneum molecular mobility in the presence of natural moisturizers.

The outermost layer of the skin, the stratum corneum (SC), is a lipid-protein membrane that experiences considerable osmotic stress from a dry and cold climate. The natural moisturizing factor (NMF) comprises small and polar substances, which like osmolytes can protect living systems from osmotic stress. NMF is commonly claimed to increase the water content in the SC and thereby protect the skin from dryness. In this work we challenge this proposed mechanism, and explore the influence of NMF on the lipid and protein components in the SC. We employ natural-abundance (13)C solid-state NMR methods to investigate how the SC molecular components are influenced by urea, glycerol, pyrrolidone carboxylic acid (PCA), and urocanic acid (UCA), all of which are naturally present in the SC as NMF compounds. Experiments are performed with intact SC, isolated corneocytes and model lipids. The combination of NMR experiments provides molecularly resolved qualitative information on the dynamics of different SC lipid and protein components. We obtain completely novel molecular information on the interaction of these NMF compounds with the SC lipids and proteins. We show that urea and glycerol, which are also common ingredients in skin care products, increase the molecular mobility of both SC lipids and proteins at moderate relative humidity where the SC components are considerably more rigid in the absence of these compounds. This effect cannot be attributed to increased SC water content. PCA has no detectable effect on SC molecular mobility under the conditions investigated. It is finally shown that the more apolar compound, UCA, specifically influences the mobility of the SC lipid regions. The present results show that the NMF components act to retain the fluidity of the SC molecular components under dehydrating conditions in such a way that the SC properties remain largely unchanged as compared to more hydrated SC. These findings provide a new molecular insight into how small polar molecules in NMF and skin care products act to protect the human skin from drying.

Using patients' narratives to reveal gender stereotypes among medical students.

PURPOSE: Gender bias exists in patient treatment, and, like most people, health care providers harbor gender stereotypes. In this study, the authors examined the gender stereotypes that medical students hold about patients. METHOD: In 2005, in Umeå, Sweden, the authors collected 81 narratives written by patients who had undergone cancer treatment; all information that might reveal the patients' gender was removed from the texts. Eighty-seven medical students read 40 or 41 narratives each, guessed the patient's gender, and explained their guess. The authors analyzed the students' explanations qualitatively and quantitatively to reveal the students' gender stereotypes and to determine whether those stereotypes had any predictive value for correctly guessing a patient's gender. RESULTS: The students' explanations contained 21 categories of justifications, 12 of which were significantly associated with the students guessing one gender or the other. Only three categories successfully predicted a correct identification of gender; two categories were more often associated with incorrect guesses. CONCLUSIONS: Medical students enter their training program with culturally shared stereotypes about male and female patients that could cause bias during their future careers as physicians. To prevent this, medical curricula must address gender stereotypes and their possible consequences. The impact of implicit stereotypes must be included in discussions about gender bias in health care.

Comparing gender awareness in Dutch and Swedish first-year medical students--results from a questionaire.

BACKGROUND: To ascertain good and appropriate healthcare for both women and men implementation of gender perspectives in medical education is needed. For a successful implementation, knowledge about students' attitudes and beliefs about men, women, and gender is crucial. The aim of this study was to compare attitudes to gender and gender stereotyping among Dutch and Swedish male and female medical students. METHODS: In this cross-sectional study, we measured the attitudes and assumptions about gender among 1096 first year medical students (616 Dutch and 480 Swedish) with the validated Nijmegen Gender Awareness in Medicine Scale (N-GAMS). The response rate was 94% in the Netherlands and 93% in Sweden. Univariate analysis of variance (ANOVA) was used to compare the scores between Dutch and Swedish male and female students. Linear regressions were used to analyze the importance of the background variables. RESULTS: There were significant differences in attitudes to gender between Dutch and Swedish students. The Swedish students expressed less stereotypical thinking about patients and doctors and the Dutch were more sensitive to gender differences. The students' sex mattered for gender stereotyping, with male students in both countries agreeing more with stereotypical statements. Students' age, father's birth country and mother's education level had some impact on the outcome. CONCLUSIONS: There are differences between cultures as well as between men and women in gender awareness that need to be considered when implementing gender in medical education.This study suggests that to arouse the students' interest in gender issues and make them aware of the significance of gender in medical work, the examples used in discussions need to be relevant and challenging in the context of the specific country. Due to different levels of knowledge and different attitudes within the student population it is important to create a climate for dialogue where students feel permitted to disclose their ideas and attitudes in order to become aware of what these are as well as their possible consequences on interaction and decision-making in medical work.

Is it possible to identify patient's sex when reading blinded illness narratives? An experimental study about gender bias.

BACKGROUND: In many diseases men and women, for no apparent medical reason, are not offered the same investigations and treatment in health care. This may be due to staff's stereotypical preconceptions about men and women, i.e., gender bias. In the clinical situation it is difficult to know whether gender differences in management reflect physicians' gender bias or male and female patients' different needs or different ways of expressing their needs. To shed some light on these possibilities this study investigated to what extent it was possible to identify patients' sex when reading their blinded illness narratives, i.e., do male and female patients express themselves differently enough to be recognised as men and women without being categorised on beforehand? METHODS: Eighty-one authentic letters about being diseased by cancer were blinded regarding sex and read by 130 students of medicine and psychology. For each letter the participants were asked to give the author's sex and to explain their choice. The success rates were analysed statistically. To illuminate the participants' reasoning the explanations of four letters were analysed qualitatively. RESULTS: The patient's sex was correctly identified in 62% of the cases, with significantly higher rates in male narratives. There were no differences between male and female participants. In the qualitative analysis the choice of a male writer was explained by: a short letter; formal language; a focus on facts and a lack of emotions. In contrast the reasons for the choice of a woman were: a long letter; vivid language; mention of emotions and interpersonal relationships. Furthermore, the same expressions were interpreted differently depending on whether the participant believed the writer to be male or female. CONCLUSION: It was possible to detect gender differences in the blinded illness narratives. The students' explanations for their choice of sex agreed with common gender stereotypes implying that such stereotypes correspond, at least on a group level, to differences in male and female patients' illness descriptions. However, it was also obvious that preconceptions about gender obstructed and biased the interpretations, a finding with implications for the understanding of gender bias in clinical practice.

Low-voltage electrohydrodynamic (EHD) spray drying of respirable particles.

Spray drying is a widely used process to produce pharmaceutical powders. In traditional spray drying, the particle size distribution is wide and not well controlled. Using EHD atomization for spray drying offers a possibility to tailor the particle size and morphology. In conventional EHD spray drying, the generated particles are charged and need to be discharged to avoid Rayleigh breakup. Discharging adds complexity to the process and eliminates the possibility to collect the powder using an electric field. The present work describes a novel EHD spray drying setup based on a low-voltage nozzle. The low-voltage nozzle imparts moderate charge to the droplets, which makes discharging unnecessary. The charged particles can be controlled and collected by using an auxiliary electric field. The EHD spray dryer has been characterized in terms of particle size, particle morphology, process output, and yield. The size distribution of the generated particles is very narrow. Both porous and completely spherical particles can be produced. The yield of small-scale bench-top equipment was 20%, which is similar to the yield of a small-scale conventional spray dryer. The effective output with five nozzles was 75 mg/hr of dry powder. Because of the repelling forces associated with the unipolarly charged droplets, the number of nozzles can be increased without risking coalescence.

Wet powder processing of sol-gel derived mesoporous silica-hydroxyapatite hybrid powders.

This paper describes a method by which a porous silica coating layer can be obtained on different apatite particles through a simple sol-gel synthesis route. Sol-gel derived powders of hydroxyapatite (HAP) and beta tricalciumphosphate (beta-TCP) were coated with a mesoporous silica using C16TAB (hexadecyltrimethylammonium bromide) as a template in order to induce mesophase formation. Further calcination of the material removes the template from the mesophase and leaves a highly ordered hexagonal arranged mesoporous silica structure with a core of HAP/beta-TCP. The phase purity of the SiO2/apatite composites has been thoroughly investigated by the means of FT-IR, XRD, and solid state 31P MAS NMR. The phase purity of these materials is shown to be dependent on the solubility properties of the used apatites. The hybrid materials are suitable as a multifunctional biomaterial where osteoconductive properties can be combined with drug delivery.

Sol-gel synthesis of a multifunctional, hierarchically porous silica/apatite composite.

In this study, a degradable, hierarchically porous silica/apatite composite material is developed from a simple low-temperature synthesis. Mesoporosity is induced in the silica portion by the use of supramolecular templating. The template is further removed by calcination. Firstly, hydroxyapatite is synthesized through a sol-gel method at near room temperature conditions. After the mineralization process, the crystal surface is coated with a mesoporous silica matrix using the templates already present in the bulk solution. The material is characterized by XRD, N(2)-sorption, FT-IR, SEM/EDS, and TEM. The coating layer is distributed fairly homogeneously over the apatite surface and the coating thickness is easily adjustable and dependent on the amount of added silica precursor. The hybrid material is shown to efficiently induce calcium phosphate formation under in vitro conditions and simultaneously work as a carrier system for drugs.

HER-2/neu (c-erbB-2) evaluation in primary breast carcinoma by fluorescent in situ hybridization and immunohistochemistry with special focus on intratumor heterogeneity and comparison of invasive and in situ components.

We have studied the intratumor HER-2/neu heterogeneity in 78 consecutive and population-based primary invasive breast carcinomas. Within the invasive component, heterogeneity was detected in only 1 of 78 tumors. In 48 tumors (62%), we found both in situ and invasive components in analyzed tissue sections. Twelve of these 48 tumors had a difference of at least 2 arbitrary units in the in situ compared with the invasive part of the tumor with regard to the HER-2/neu status analyzed by HercepTest (immunohistochemistry). Eight of these 12 tumors were reanalyzed with fluorescent in situ hybridization and immunohistochemistry with and without a new Automated Cellular Imaging System. In this limited material, immunohistochemistry in combination with the Automated Cellular Imaging System seemed to have a better correlation with fluorescent in situ hybridization than immunostaining analyzed manually. In conclusion, HER-2/neu expression is not seldom heterogeneous in invasive compared with in situ components within a tumor. This finding should be considered in the choice of evaluation method. To avoid heterogeneity as a confounding factor in HER-2/neu analyses, detection methods such as immunohistochemistry and fluorescent in situ hybridization, which can provide evaluation in a preserved tissue architecture, should be used. Perhaps the intratumor HER-2/neu heterogeneity can explain some of the unexpected failures of trastuzumab therapy.