bluuebunny/crossref_metadata_2025 huggingface dataset:
Offspring sex ratio variation in relation to brood size and mortality in a promiscuous species: the Aquatic Warbler Acrocephalus paludicola
Authors: Dyrcz Andrzej , Sauer‐Gürth Hedi , Tkadlec Emil , Wink Michael
Published: December 2004

We analyse nestling sex ratio variation in the Aquatic Warbler Acrocephalus paludicola to test for predictions from sex allocation theory that the brood sex ratio is close to parity. We also tested Fiala's (1980) prediction that there is no difference in sex ratio between broods affected and not affected by mortality, and whether a shift in primary sex ratios or simple differential mortality by sex underlies that difference. Furthermore, we explore additional analytical possibilities for inferring proximate mechanisms through simulation modelling. In the Aquatic Warbler, which is promiscuous, the overall sex ratio determined by molecular sexing of nestlings at 8–11 days of age did not deviate significantly from parity (proportion of females 0.509), nor did we find any predictive effect of brood size, maternal body mass, fat condition, wing and bill length, laying date, mean daily temperature, and multiple‐male mating. However, extensive simulation suggested that the whole pattern of sex ratio variation is unlikely to arise purely by chance: (1) there is a diverging sex ratio between complete and partial broods, (2) large broods tended to be female‐biased and small broods male‐biased, and (3) low ambient temperature prior to the laying period seemed to increase the proportion of female offspring in complete broods. We conclude that most variation in nestling sex ratio is non‐adaptive in nature, and results from variation in female nestlings mortality dependent on brood size and sex ratio.
Effects of Medicaid Managed Care Programs on Health Services Access and Use
Authors: Garrett Bowen , Davidoff Amy J. , Yemane Alshadye
Published: December 2004

Objective. To estimate the effects of Medicaid managed care (MMC) programs on Medicaid enrollees’ access to and use of health care services at the national level.

Data Sources/Study Setting 1991–1995 National Health Interview Surveys (NHIS) and a 1998 Urban Institute survey on state Medicaid managed care programs.

Study Design. Using multivariate regression models, we estimated the effect of living in a county with an MMC program on several access and use measures for nonelderly women who receive Medicaid through AFDC and child Medicaid recipients. We focus on mandatory programs and estimate separate effects for primary care case management (PCCM) programs, health maintenance organization (HMO) programs, and mixed PCCM/HMO programs, relative to fee‐for‐service (FFS) Medicaid. We control for individual and county characteristics, and state and year effects.

Data Collection/Extraction Method. This study uses pooled individual‐level data from up to five years of the NHIS (1991–1995), linked to information on Medicaid managed care characteristics at the county level from the 1998 MMC survey.

Principal Findings We find virtually no effects of mandatory PCCM programs. For women, mandatory HMO programs reduce some types of non–emergency room (ER) use, and increase reported unmet need for medical care. The PCCM/HMO programs increase access, but had no effects on use. For children, mandatory HMO programs reduce ER visits, and increase the use of specialists. The PCCM/HMO programs reduce ER visits, while increasing other types of use and access.

Conclusions Mandatory PCCM/HMO programs improved access and utilization relative to traditional FFS Medicaid, primarily for children. Mandatory HMO programs caused some access problems for women.
Improving Care for Minorities: Can Quality Improvement Interventions Improve Care and Outcomes For Depressed Minorities? Results of a Randomized, Controlled Trial
Authors: Miranda Jeanne , Duan Naihua , Sherbourne Cathy , Schoenbaum Michael , Lagomasino Isabel , Jackson‐Triche Maga , Wells Kenneth B.
Published: December 2004

Objective. Ethnic minority patients often receive poorer quality care and have worse outcomes than white patients, yet practice‐based approaches to reduce such disparities have not been identified. We determined whether practice‐initiated quality improvement (QI) interventions for depressed primary care patients improve care across ethnic groups and reduce outcome disparities.

Study Setting. The sample consists of 46 primary care practices in 6 U.S. managed care organizations; 181 clinicians; 398 Latinos, 93 African Americans, and 778 white patients with probable depressive disorder.

Study Design. Matched practices were randomized to usual care or one of two QI programs that trained local experts to educate clinicians; nurses to educate, assess, and follow‐up with patients; and psychotherapists to conduct Cognitive Behavioral Therapy. Patients and physicians selected treatments. Interventions featured modest accommodations for minority patients (e.g., translations, cultural training for clinicians).

Data Extraction Methods. Multilevel logistic regression analyses assessed intervention effects within and among ethnic groups.

Principal Findings. At baseline, all ethnic groups (Latino, African American, white) had low to moderate rates of appropriate care and the interventions significantly improved appropriate care at six months (by 8–20 percentage points) within each ethnic group, with no significant difference in response by ethnic group. The interventions significantly decreased the likelihood that Latinos and African Americans would report probable depression at months 6 and 12; the white intervention sample did not differ from controls in reported probable depression at either follow‐up. While the intervention significantly improved the rate of employment for whites and not for minorities, precision was low for comparing intervention response on this outcome. It is important to note that minorities remained less likely to have appropriate care and more likely to be depressed than white patients.

Conclusions. Implementation of quality improvement interventions that have modest accommodations for minority patients can improve quality of care for whites and underserved minorities alike, while minorities may be especially likely to benefit clinically. Further research needs to clarify whether employment benefits are limited to whites and if so, whether this represents a difference in opportunities. Quality improvement programs appear to improve quality of care without increasing disparities, and may offer an approach to reduce health disparities.
Does Satisfaction Reflect the Technical Quality of Mental Health Care?
Authors: Edlund Mark J. , Young Alexander S. , Kung Fuan Yue , Sherbourne Cathy D. , Wells Kenneth B.
Published: December 2004

Objective. To analyze the relationship between satisfaction and technical quality of care for common mental disorders.

Data Source. A nationally representative telephone survey of 9,585 individuals conducted in 1997–1998.

Study Design. Using multinomial logistic regression techniques we investigated the association between a five‐level measure of satisfaction with the mental health care available for personal or emotional problems and two quality indicators. The first measure, appropriate technical quality, was defined as use of either appropriate counseling or psychotropic medications during the prior year for a probable depressive or anxiety disorder. The second, active treatment, indicated whether the respondent had received treatment for a psychiatric disorder in the past year. Covariates included measures of physical and mental health and sociodemographic indicators.

Principal Findings. Appropriate technical quality of care was significantly associated with higher levels of satisfaction. The strength of the association was moderate.

Conclusions. Satisfaction is associated with technical quality of care. However, profiling quality of care with satisfaction will likely require large samples and case‐mix adjustment, which may be more difficult for plans or provider groups to implement than measuring technical indicators. More importantly, satisfaction is not the same as technical quality, and our results suggest that at this time they cannot be made to approach each other closely enough to eliminate either.
Callers' Ability to Understand Advice Received from a Telephone Health‐Line Service: Comparison of Self‐Reported and Registered Data
Authors: Leclerc Bernard‐Simon , Dunnigan Lise , Côté Harold , Zunzunegui Maria‐Victoria , Hagan Louise , Morin Diane
Published: December 2004

Objective. To validate users' perception of nurses' recommendations to look for another health resource among clients seeking teleadvice. To analyze the effects of different users' and call characteristics on the incorrectness of the self‐report.

Data Sources/Study Setting. This study is a secondary analysis of data obtained from 4,696 randomly selected participants in a survey conducted in 1997 among users of Info‐Santé CLSC, a no‐charge telenursing health‐line service (THLS) available all over the province of Québec.

Study Design/Data Collection. Self‐reported advice from follow‐up survey phone interviews, conducted within 48 to 120 hours after the participant's call, were compared to the data consigned by the nurse in the computerized call record. Covariables concerned characteristics of callers, context of the calls, and satisfaction about the nurses' intervention. Association between these variables and inaccurate reports was identified using multinomial logistic regression analyses.

Principal Findings. Advice to consult were recorded by the nurse in 42 percent of cases, whereas 39 percent of callers stated they had received one. Overall disagreement between the two sources is 27 percent (12 percent by false positive and 15 percent by false negative) and kappa is 0.45. Characteristics such as living alone (adjusted OR=2.5), calls relating to psychological problems (OR=2.8), perceived seriousness (OR=∼2.6), as well as others, were associated with inaccurate reports.

Conclusions. Telephone health‐line providers should be aware that many callers appear to interpret advice to seek additional health care differently than intended. Our findings suggest the need for continuing quality control interventions to reduce miscommunication, insure better understanding of advice by callers, and contribute to more effective service.
Health Care Costs among Smokers, Former Smokers, and Never Smokers in an HMO
Authors: Fishman Paul A. , Khan Zeba M. , Thompson Ella E. , Curry Susan J.
Published: December 2004

Objective. We estimate long‐term health care costs of former smokers compared with continuing and never smokers using a retrospective cohort study of HMO enrollees. Previous research on health care costs associated with former smokers has suggested that quitters may incur greater health care costs than continuing smokers, therefore, getting people to quit creates more expensive health care consumers. We studied the trend in cost for former smokers over seven years after they quit to assess how the cessation experience impacts total health care cost.

Data Sources/Study Setting. Group Health Cooperative (GHC), a nonprofit mixed model health maintenance organization in western Washington state.

Study Design. Retrospective cohort study using automated and primary data collected through telephone interviews.

Principal Findings. We find that former smokers' costs are significantly greater (p<.05) in the year immediately following cessation relative to continuing smokers, but former smokers' costs fall in year two. This decrease maintains throughout the six‐year follow‐up period. Although former smokers cost more than continuing smokers in the year after cessation, this increase appears to be transient. Long‐term costs for former smokers are not statistically different from those of continuing smokers and cumulative health care expenses are lower by the seventh year postquit. Our evidence suggests that smoking cessation does not increase long‐term heath care costs.

Conclusions. Health care costs among former smokers increase relative to continuing smokers in the year after cessation but fall to a level that is statistically indistinguishable in the second year postquit. Any net increase in costs among former smokers relative to continuing smokers appears compensated for within two years post‐quit and is maintained for at least six years after cessation.
Fighting for Other Folks’ Wages: The Logic and Illogic of Living Wage Campaigns
Authors: FREEMAN RICHARD
Published: December 2004

Living wage campaigns have enacted ordinances/policies to raise low wages in over 100 localities. The campaigns galvanize citizens more than national economic issues and allow for pay increases fine‐tuned to local realities, but cover relatively few workers. To help the low‐paid broadly, the coalitions in living wage campaigns have to scale up to the state or national level while unions and national groups work to devolve labor issues from the gridlock at the federal level to states and localities.
The Economic Impact of the Boston Living Wage Ordinance*
Authors: BRENNER MARK D.
Published: December 2004

This paper presents one of the first quantitative assessments of the effect living wage laws have had on firms covered by their mandate. Applying difference‐in‐difference estimation methods to survey data from Boston, Massachusetts, I find little evidence of reduced employment or hours worked, following living wage implementation. Instead, there is strong evidence that firms actually shifted from part‐time towards full‐time staffing as a result of Boston's living wage law. Estimates also reveal a substantial degree of wage compression within firms who raised wages. Finding no evidence of reduced employment or hours, this paper uses qualitative survey data to examine other ways in which firms may have adjusted to higher wages. I find some evidence that covered firms have taken lower profits as a way to adjust to the Boston law.
The Impact of Living Wages on Employers: A Control Group Analysis of the Los Angeles Ordinance*
Authors: FAIRRIS DAVID
Published: December 2004

This paper analyzes the impact of the Los Angeles Living Wage Ordinance on employers using two original data sets and a quasi‐experimental research design. Relative to a control group of establishments, the starting pay of low‐wage workers has risen by $1.74 per hour, paid days off have risen by two days, and employer‐paid health benefits have not significantly changed among establishments covered by the living wage ordinance. Living wage establishments have witnessed a sizeable reduction in low‐wage worker turnover, a drop in absenteeism, reduced overtime hours, and reduced job training relative to the control group of establishments. The ordinance appears to have had no significant impact on the use of part‐time workers, the intensity of supervision, or the tendency of living wage firms to fill vacancies from within.
Recent Publications
Authors: HUWE TERENCE K. , KIMBALL JANICE
Published: December 2004

Books reviewed:

David Bacon, The Children of NAFTA.

Laurence J. Kotlikoff and Scott Burns, The Coming Generational Storm: What You Need to Know About America's Economic Future.

Pablo J. Boczkowski, Digitizing the News: Innovation in Online Newspapers.

Frank Levy and Richard J. Murnane, The Division of Labor: How Computers Are Creating the Next Job Market.

Dominque Foray, The Economics of Knowledge.

Martin Campbell‐Kelly, From Airline Reservations to Sonic the Hedgehog: A History of the Software Industry.

Rick Fantasia and Kim Voss, Hard Work: Remaking the American Labor Movement.

Brian K. Obach, Labor and the Environmental Movement: The Quest for Common Ground.

Chris Rhomberg, No There There: Race, Class and Political Community in Oakland.

Daniel Cohen, Our Modern Times: The Nature of Capitalism in the Information Age.

Steven Henry Lopez, Reorganizing the Rust Belt: An Inside Study of the American Labor Movement.

Bruce Sinclair ed., Technology and the African‐American Experience: Needs and Opportunities for Study.
Early prostate cancer detected using expression of non‐functional cytolytic P2X7 receptors
Authors: Slater M , Danieletto S , Gidley‐Baird A , Teh L C , Barden J A
Published: December 2004

Aims:  To detect early prostate cancer reliably by monitoring the expression of non‐functional P2X7 cytolytic purinergic receptors.

Methods and results:  P2X7 receptors were absent from normal prostate epithelium obtained from post mortem tissue and tissue from cases of transurethral resection collected from young men (n = 23) who were confirmed to be free of cancer at later procedures 5–10 years after collection of the original samples. However, P2X7 was present in every case of 116 confirmed prostate cancers regardless of Gleason grade or patient age. P2X7 was present in apparently normal epithelial cells in acini well outside the tumour margins, but appeared in a distinct stage‐specific manner commencing with the nucleus, progressing to the cytoplasm and collecting finally on the apical membrane of the epithelial cells in morphologically distinct cancer. The pattern of P2X7 receptor localization in the epithelial cells was recorded in earlier biopsies obtained from the same patient cohort. One hundred and fourteen of 116 prostates stained positively for P2X7 at the earliest biopsy, though generally with a less advanced pattern of distribution.

Conclusions:  The appearance of P2X7 receptors in normal prostate tissue adjacent to prostate tumours makes direct tumour biopsy less critical for positive cancer diagnosis and enables cancer progression to be monitored.
Atypical pleomorphic epithelioid angiomyolipoma localized to the pelvis: a case report and review of the literature
Authors: Gronchi A , Diment J , Colecchia M , Fiore M , Santinami M
Published: December 2004

Aims:  Angiomyolipoma is the most common mesenchymal tumour of the kidney. It has been reported in several other sites outside the kidney, mainly in the liver. We report the first case of atypical pleomorphic angiomyolipoma in a man, arising from the pouch of Douglas and extending to the entire abdominal cavity.

Methods:  A 17‐year‐old man underwent a complete resection of a giant abdominopelvic mass. The tissue was formalin fixed and paraffin embedded and 4 µm thick histological sections were stained with haematoxylin–eosin. Immunohistochemical stains for HMB‐45, smooth muscle actin, vimentin, calponin, S100 and desmin were performed. Sections for electron microscopy were also prepared.

Results:  Microscopic examination revealed a neoplasm composed of pleomorphic epithelioid cells with atypical features, immunoreactive for HMB‐45, MART‐1, actin, vimentin and calponin, while S100 protein and desmin stains were negative. Ultrastructurally, the tumour cells showed prominent nucleoli, vacuolated cytoplasm, and some premelanosomes. A diagnosis of atypical pleomorphic epithelioid angiomyolipoma was then made.

Conclusions:  To date five patients with abdominal epithelioid angiomyolipoma have been described in the literature. All were women. Three of the five patients reported developed metastasis, while our patient is still free of disease at 16 months of follow‐up. Clear prognostic pathological features have not been identified.
Morphologically distinct patterns of apoptosis correlate with size and high‐grade dysplasia in colonic adenomas
Authors: Brodie C M , Crotty P L , Gaffney E F
Published: December 2004

Aims:  To examine the relationship of morphological patterns of apoptosis in colonic adenomas to standard pathological variables.

Methods and results:  Apoptosis patterns were evaluated in 184 consecutive colonic adenomas and 14 adenocarcinomas, using haematoxylin and eosin sections. Apoptosis identification was selectively validated by electron microscopy. There were three patterns of apoptosis: (i) confluent basal apoptosis; (ii) crypt lumen apoptosis, both assessed semiquantitatively; and (iii) scattered apoptosis (not quantified). Adenoma site, size, type, mitoses, and grade of dysplasia were also assessed. MIB‐1 immunostaining was performed in 20 cases. In 142 adenomas (77%) confluent basal apoptosis (n = 124) and/or crypt lumen apoptosis (n = 69) were identified; 42 (23%) had scattered apoptosis only. Significant correlations were: (i) extensive confluent basal apoptosis with small adenomas ≤5 mm (P < 0.0001); (ii) crypt lumen apoptosis with large adenomas >5 mm (P < 0.0001) and (iii) with high‐grade dysplasia (P < 0.0003); and (iv) coexistence of both patterns (n = 51) with large adenomas >5 mm (P < 0.0001). Neither apoptosis pattern correlated with other variables. Adenocarcinomas had minimal confluent basal apoptosis (5/14), conspicuous crypt lumen apoptosis (14/14), intraglandular coagulative necrosis, and scattered apoptotic tumour cells.

Conclusions:  Confluent basal apoptosis is maximal early in colonic tumorigenesis. The ‘switch’ to a predominant crypt lumen apoptosis pattern suggests that a different apoptosis induction mechanism might be associated with the transition to adenocarcinoma.
Expression of matrix metalloproteinases MMP‐2, MMP‐9 and their tissue inhibitors TIMP‐1, ‐2, and ‐3 in benign and malignant tumours of the salivary gland
Authors: Nagel H , Laskawi R , Wahlers A , Hemmerlein B
Published: December 2004

Aims:  The balance between matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) is involved in the morphogenesis of the normal salivary gland as well as in mechanisms of tumour invasion and metastasis. Our aim was to analyse protein and mRNA expression of MMPs and TIMPs in normal salivary gland tissue and in various salivary gland neoplasms.

Methods and results:  Immunohistochemistry for MMP‐2, MMP‐9, TIMP‐1, ‐2 and ‐3 was performed in 20 malignant and six benign salivary gland tumours. The immunoscores of MMP‐2 were significantly higher in carcinomas compared with adenomas (P = 0.0028). The MMP/TIMP ratio was significantly higher in carcinomas than in adenomas (P = 0.0097). In mucoepidermoid carcinomas MMP‐2 expression was preferentially observed in the intermediate cell type. Neoplastic acinar cells of acinic cell carcinoma demonstrated de novo expression of MMP‐2, MMP‐9, TIMP‐1, and TIMP‐2. Immunoscores of TIMP‐3 were not decreased in malignant tumours compared with adenomas. In accordance with the immunostaining of MMP‐2 and ‐9, gelatinolytic activity could be demonstrated by in‐situ zymography. The mRNA expression of MMPs and TIMPs analysed by real‐time reverse transcriptase‐polymerase chain reaction in three malignant and two benign tumours and their corresponding normal tissue did not generally correlate with their protein expression.

Conclusions:  Our findings suggest a disturbed balance between MMP and TIMP in malignant salivary gland tumours. MMP‐2 expression in particular seems to be related to the invasive properties and the malignant potential of these tumours.
Expression of Bcl‐2 family members and presence of Epstein–Barr virus in the regulation of cell growth and death in classical Hodgkin's lymphoma
Authors: Kim L‐H , Nadarajah V S , Peh S‐C , Poppema S
Published: December 2004

Aims:  To examine the expression of the Bcl‐2 family of proteins (Bcl‐2, Bcl‐x, Bcl‐xL and Bax) in classical Hodgkin's lymphoma (cHL) and to correlate the expression of these proteins with proliferation, apoptosis and the presence of Epstein–Barr virus (EBV).

Methods and results:  Expression of the Bcl‐2 family of proteins was detected by immunohistochemistry, proliferation was determined by Ki67 labelling and apoptosis by TUNEL in‐situ hybridization. EBV was detected by Epstein–Barr virus early RNA (EBER) in‐situ hybridization. Expression of Bcl‐2, Bcl‐x, Bcl‐xL and Bax was detected in the Hodgkin/Reed–Sternberg (H/RS) cells in 43.7% (27/62), 87.5% (56/64), 67.2% (41/61) and 74.6% (47/63) of the cHL cases, respectively. EBER was detected in 53% (35/66) of the cases, whereas Ki67 was observed in 86.7% (52/60) of the cases. Apoptotic H/RS cells were observed infrequently, and only 43.2% (11/26) of the cases showed an apoptotic index of ≥ 10% in the H/RS cells. A statistically significant inverse relationship was observed between the expression of Bcl‐2 and the presence of EBV (P = 0.003). Bcl‐xL showed an inverse correlation with apoptosis in the H/RS cells (P = 0.004).

Conclusions:  The higher Bcl‐xL expression (67.2%) compared with Bcl‐2 expression (43.5%) observed in cHL as well as the statistically significant inverse relationship between Bcl‐xL and apoptosis suggests that Bcl‐xL plays an important role in the survival of H/RS cells. Expression of Bax may be neutralized by other anti‐apoptotic members of the family such as Bcl‐2 and/or Bcl‐xL.
Natural killer T cells as targets for immunotherapy of autoimmune diseases
Authors: Van Kaer Luc
Published: December 2004

CD1d‐restricted natural killer T (NKT) cells are innate lymphocytes that play a regulatory role during an immune response. The identification of α‐galactosylceramide (α‐GalCer), a marine sponge‐derived glycosphingolipid, as a potent stimulator of NKT cells led many laboratories to investigate the effects of NKT cell activation on the regulation of immune responses. These studies revealed that α‐GalCer induces rapid and robust cytokine production by NKT cells, secondary activation of a variety of innate and adaptive immune cells, and modulation of Th cell responses. Further, α‐GalCer influences disease progression in a variety of experimental models of autoimmunity and inflammation in mice, including models for type 1 diabetes, multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosus, inflammatory bowel disease, and atherosclerosis. While these studies have raised significant enthusiasm for manipulation of NKT cells as a means of preventing autoimmunity in the clinical setting, there are significant concerns regarding the safety of repeated α‐GalCer injections in human subjects.
Mast cell chymase expression in Helicobacter pylori‐associated gastritis
Authors: Matsuo T , Ikura Y , Ohsawa M , Ogami M , Kayo S , Yoshimi N , Hai E , Naruko T , Ohishi M , Higuchi K , Arakawa T , Ueda M
Published: December 2004

Aims:  To study the role of mast cell chymase in the inflammatory processes of human chronic gastritis. Experimental studies have shown that mast cell chymase stimulates inflammatory cell accumulation, and contributes to angiotensin II formation.

Methods and results:  Tissue sections from human stomachs with Helicobacter pylori‐associated gastritis (surgery/autopsy n = 20; biopsy n = 16) and normal stomachs (n = 10) were studied using immunohistochemical single and double labelling techniques. Monoclonal antibodies used were directed against mast cell chymase, tryptase, neutrophils (CD66b, elastase, and myeloperoxidase), macrophages, T‐lymphocytes, and interleukin (IL)‐4. The expression of angiotensin‐converting enzyme and angiotensin II type 1 receptor was investigated using immunohistochemical analysis and the reverse transcription‐polymerase chain reaction. The number of chymase‐positive mast cells was significantly higher (P < 0.0001) in H. pylori‐associated gastritis than in normal stomachs. Increased expression of chymase in inflamed mucosa was closely related to an increase in the accumulation of neutrophils, macrophages, T‐lymphocytes, and IL‐4‐positive cells. The expression of angiotensin‐converting enzyme and angiotensin II type 1 receptor was not altered in gastritis specimens.

Conclusions:  These observations suggest that mast cell chymase may be an important mediator in the inflammatory processes of human H. pylori‐associated gastritis.
Tie‐1 tyrosine kinase expression in human thyroid neoplasms
Authors: Ito Y , Yoshida H , Uruno T , Nakano K , Takamura Y , Miya A , Kobayashi K , Yokozawa T , Matsuzuka F , Kuma K , Miyauchi A
Published: December 2004

Aims:  To investigate tie‐1 expression in human thyroid neoplasms. Recent studies have demonstrated that receptor‐type tyrosine kinases (RTKs) contribute to carcinoma progression. Tie‐1 is one of the RTKs and plays a role in angiogenesis, although its pathophysiological significance in human carcinoma is still to be elucidated.

Methods and results:  Immunohistochemical expression of tie‐1 was studied in various thyroid neoplasms. Tie‐1 immunoreactivity was only occasionally observed in normal follicular cells. In papillary carcinoma, tie‐1 was classified as positive in carcinoma cells in 55.7% of the cases and was more frequently expressed in those of smaller size with an absence of a poorly differentiated lesion. In contrast, tie‐1 was positive in only 8.3% of anaplastic carcinoma and no cases of follicular carcinoma or adenoma were positive.

Conclusions:  These results suggest that tie‐1 has a role in thyroid tumorigenesis, especially in the early phase of papillary carcinoma, but it is not important in the progression of anaplastic carcinoma or follicular tumour.
Proximal small‐bowel mucosal villous intraepithelial lymphocytes
Authors: Goldstein N S
Published: December 2004

Small‐bowel biopsies are routinely obtained from adult patients as a screening tool to evaluate the possibility of gluten sensitivity (GS). Previous morphological criteria of GS including completely flattened villi are usually absent. In the context of screening for GS, an altered distribution density pattern of villous intraepithelial lymphocytes (IELs) is probably the most sensitive morphological feature to suggest the possibility of GS and prompt the initiation of further medical evaluation. Altered villous IEL density distribution is a more sensitive screening feature than villous IEL counts. With increased small‐bowel GS screening biopsies, occasional adults without GS with complete villous flattening and numerous villous IELs are encountered. These patients are usually incorrectly diagnosed with GS. However, they do not respond to a gluten‐free diet and slowly improve over months.
Clear‐cell proliferation of the lung with lymphangioleiomyomatosis‐like change
Authors: Pileri S A , Cavazza A , Schiavina M , Zompatori M , Pederzoli M , Goldfischer M , Sabattini E , Ascani S , Pasquinelli G , Bonetti F , Colby T V
Published: December 2004

Aims : To describe two cases of a peculiar pulmonary lesion, which expand both the morphological and the immunophenotypic spectrum of perivascular epithelioid cell (PEC)‐related disorders.

Methods and results : One man and one female, with and without the tuberous sclerosis complex (TSC), respectively, showed pulmonary cysts and small nodules on computed tomography scan. In the former, lymphangioleiomyomatosis (LAM) was suspected. In both cases, an open lung biopsy was performed, whose cut surface displayed numerous cysts lined by thin/thick septa. Microscopically, the septa were associated with micronodular or interstitial proliferation of medium/large‐sized elements with abundant clear (periodic acid–Schiff‐positive/diastase‐sensitive) cytoplasm and distinct cell borders, embedded in fibrous tissue. The elements were CD34+, vimentin‐positive and, to a lesser extent, HMB‐45+ and MART‐1+. The stains for specific muscle actin, desmin, S100 protein, CD31, FVIIIRAg, cytokeratins, CD45, CD68, oestrogen and progesterone receptors were all negative. Ki67 labelling was <1%. Electron microscopy displayed cytoplasmic vacuoles containing glycogen particles. The TSC1 and TSC2 gene status could not be assessed because of poor DNA preservation. In the man with TSC, a focus of micronodular pneumocyte hyperplasia was also found.

Conclusions : Because of the coexpression of CD34 and melanoma‐associated antigens and the occurrence of TSC in one patient, the cases described here add a new piece to the puzzle of PEC lesions and contribute to the open discussion on the origin of LAM and LAM‐like proliferations.
Post mortem sampling of the brain and other tissues in neurodegenerative disease
Authors: Love S
Published: December 2004

The importance of the autopsy in neurodegenerative disease is often not appreciated. Yet clinical diagnosis of neurodegenerative disease is relatively inaccurate, many neurodegenerative diseases are inherited or are associated with specific genetic risk factors, and several non‐transmissible neurodegenerative diseases may be confused clinically with prion diseases. In all these cases, the autopsy is the only practical way in which brain tissue can be obtained for diagnosis. The pathologist should ensure that consent by the next‐of‐kin to post mortem examination is based on clear information as to the nature, scope and limitations of the autopsy, and that any constraints on retaining brain and other tissues are documented. The autopsy should be preceded by a careful review of the clinical notes and ante mortem studies, and consideration of the possible and likely pathological processes. This may suggest the need to retain fixed or frozen samples of cerebrospinal fluid, skeletal muscle, peripheral nerve and other tissues in addition to brain and spinal cord. Ideally, the brain should be fixed intact for 2–3 weeks before it is sliced and blocks are taken. If the period of fixation is limited to a few days only, it is best to slice the brain whilst it is fresh and to allow the diagnostically relevant slices to fix flat; after about 3 days the fixed slices can be sliced further, examined macroscopically and sampled. Even if consent is limited to the retention of only a few tissue samples for histology, a reasonably confident diagnosis can still usually be made, provided that the sampling is careful and systematic. The selection of blocks or brain and spinal cord for histology should be based on internationally accepted guidelines for the pathological diagnosis of different types of neurodegenerative disease, where such guidelines are available. Illustrations are provided to indicate which regions of the brain are critical to establishing a diagnosis in the main categories of neurodegenerative disease. When difficulties arise in the pathological diagnosis of neurodegenerative disease, inadequate post mortem sampling or rapid processing of poorly fixed brain tissue is usually to blame.
Galectin‐3: differential expression between small‐cell and non‐small‐cell lung cancer
Authors: Buttery R , Monaghan H , Salter D M , Sethi T
Published: December 2004

Aims:  To compare the histological expression of galectin‐3 in different lung cancers, including small‐cell lung cancer (SCLC) and non‐small‐cell lung cancer (NSCLC). Lung cancer is the leading cause of cancer deaths in the UK. Galectin‐3 is a β‐galactoside binding protein with a controversial role in malignant transformation. SCLC metastasizes early and is initially chemosensitive; NSCLC metastasizes later, offering the chance of surgical cure, but is much less chemosensitive. Mixed tumours present a diagnostic and therapeutic problem, with a poorer response to therapy. Insight into the cellular mechanisms that govern metastasis and chemoresistance will profoundly influence the future management of this disease.

Methods and results:  In this study the histological expression of galectin‐3 was assessed in a panel of lung tumour specimens, using the indirect streptavidin–biotin method. A striking difference in galectin‐3 expression was observed between tumours, with high expression in NSCLC (42/47 samples) and low expression in SCLC (negative in 13/18, weak in 5/18).

Conclusion:  This differential expression of galectin‐3 between histological types of lung carcinoma suggests that galectin‐3 may have an important influence on tumour cell adhesion, apoptosis and the response of tumours to chemotherapy.
Post‐transplant T‐cell lymphoproliferative disorder/T‐cell lymphoma: a report of three cases of T‐anaplastic large‐cell lymphoma with cutaneous presentation and a review of the literature
Authors: Coyne J D , Banerjee S S , Bromley M , Mills S , Diss T C , Harris M
Published: December 2004

Aims:  To report the clinical, pathological and immunohistochemical features of three cases of post‐transplant T‐cell lymphoproliferative disorder (T‐PTLD) T‐cell lymphoma with primary cutaneous presentation.

Methods and results:  Three cases of primary cutaneous post‐transplantation anaplastic large‐cell lymphomas occurred in renal transplant recipients and were shown to display a T‐cell immunophenotype; all were ALK 1 protein and EMA negative and two were Epstein–Barr virus positive using in‐situ hybridization. Two displayed a CD4+ phenotype, two were focally CD56+ and all three were negative for the cytolytic enzyme granzyme B. In two cases monoclonality was established by T‐cell receptor gene rearrangement study. All presented with nodular cutaneous involvement and all were ultimately fatal.

Conclusion:  T‐PTLDs are uncommon histological subtypes both in a general context and associated with cutaneous presentation. Our findings suggest clinicopathological and immunophenotypic similarities to primary cutaneous anaplastic large‐cell lymphoma but with a progressive clinical behaviour similar to previously reported T‐PTLD and to systemic nodal ALK– anaplastic large‐cell lymphoma.
Clinicopathological significance and survival influence of p53 protein expression in gastric carcinoma
Authors: Pinto‐de‐Sousa J , Silva F , David L , Leitão D , Seixas M , Pimenta A , Cardoso‐de‐Oliveira M
Published: December 2004

Aims: Mutations in the gene coding for p53 protein are among the most frequent genetic alterations observed in human cancers. The relevance and biological significance of p53 expression in gastric carcinoma are far from being fully established. The aim of our study was to evaluate the influence of p53 detected by immunohistochemistry in the clinicopathological behaviour of a series of gastric carcinoma cases.

Methods and results: Samples from 163 patients treated by gastric resection for gastric carcinoma between 1988 and 1995 were used. Surgical specimens were evaluated for the presence of p53 protein detected by immunohistochemistry with a monoclonal antibody. Cases were classified as positive or negative for p53. Several clinicopathological parameters and c‐erbB‐2 expression were analysed in the same series and compared with the expression of p53. Cumulative survival was evaluated using univariate analysis and Cox model regression. p53 expression was identified in 41 carcinomas (25.2%) and was significantly associated with venous invasion (P = 0.049), lymph node metastases (P = 0.01) and c‐erbB‐2 expression (P = 0.003). All the parameters except gender, tumour size and Laurén's classification influenced survival on univariate analysis. p53 expression correlated with overall survival (P = 0.006) and survival in the subgroup of patients with intestinal type carcinoma (P = 0.04). In the subgroup of patients with carcinomas not expressing c‐erbB‐2, p53 expression significantly influenced cumulative survival (P = 0.02).

Conclusions: p53 expression is associated with the aggressive biological behaviour of gastric carcinomas and is related to cumulative survival.
Cyclooxygenase‐2 expression and relationship to tumour progression in human renal cell carcinoma
Authors: Hashimoto Y , Kondo Y , Kimura G , Matsuzawa I , Sato S , Ishizaki M , Imura N , Akimoto M , Hara S
Published: December 2004

Aims:  Cyclooxygenase (COX), which catalyses the synthesis of prostaglandins from arachidonic acid, has two isoforms; COX‐1 and COX‐2. There is ample evidence to suggest an important role for COX‐2 in cancer. The aim of this study was to evaluate the clinical significance of COX‐2 expression and its localization in the development and progression of human renal cell carcinoma (RCC).

Methods and results:  The expression and localization of COX‐2 were evaluated in human RCC tissues from 75 patients by immunohistochemistry. Immunoreactive COX‐2 protein was observed in all cases of RCC, and the levels of COX‐2 expression were correlated with tumour grade and pathological stage. Expression of COX‐2 was higher in the granular cell subtype than in the clear cell subtype of RCC. Immunoelectron microscopy revealed that COX‐2 was expressed in the nuclear membrane, rough endoplasmic reticulum, Golgi complex and mitochondrial membrane of RCC cells.

Conclusion:  COX‐2 overexpression within these intracellular organelles in RCC may be associated with renal cell carcinogenesis and COX‐2 may be a useful biomarker in RCC.
CD27 distinguishes two phases in bone marrow infiltration of splenic marginal zone lymphoma
Authors: Franco V , Florena A M , Ascani S , Paulli M , Salvato M , Pileri S A
Published: December 2004

Aims:  To investigate CD27 expression in splenic marginal zone lymphoma (SMZL), an indolent low‐grade B‐cell lymphoma with constant involvement of the bone marrow, especially with an intrasinusoidal pattern. It is not clear if the neoplastic clone is composed of virgin or somatically mutated B cells. CD27 is reported to be a hallmark of memory B cells.

Methods and results:  We evaluated 64 bone marrow biopsy specimens (BMBs) from 36 patients with SMZL for the expression of CD27. For comparison, splenectomy specimens of patients with traumatic splenic rupture or with SMZL were used. All BMBs showed lymphomatous infiltration. When located in the marrow sinusoids, neoplastic cells were CD27– in all cases and therefore corresponded to naive B cells. In nodular/interstitial infiltration, the cells were CD27+ and therefore corresponded to memory B cells. No difference in immunohistochemical expression of B and T antibodies was found between intrasinusoidal and interstitial/nodular infiltration. CD27 was constantly expressed in the splenic marginal zone of normal spleen, surgically removed for trauma, and in seven out of 10 spleens with SMZL.

Conclusion:  We propose the existence of two different phases of neoplastic progression with, first, expansion of a virgin B clone in the bone marrow and, following exposure to antigen, a re‐colonization of the bone marrow.
Immunohistochemistry in melanocytic proliferative lesions
Authors: De Wit N J W , Van Muijen G N P , Ruiter D J
Published: December 2004

Melanoma incidence is rising worldwide. Early diagnosis is very important, as the most effective treatment for melanoma still consists of excision of the tumour before onset of the metastatic growth phase. Immunohistochemistry is a valuable tool for (dermato)pathologists to aid establishing diagnosis. Melanoma markers can be classified into two main categories: melanocytic differentiation markers and melanoma progression markers. Melanocytic differentiation markers are mostly used to distinguish poorly differentiated melanomas from non‐melanocytic tumours and for staging of melanocytic proliferative lesions. Melanoma progression markers are most suitable to determine the level of malignancy and/or aggressiveness of tumour cells. This review describes the classification of melanoma markers, including commonly used and recently identified antigens with potential marker function. We characterize their expression profile in melanocytic proliferative lesions and their potential usefulness for diagnosis, prognosis, microstaging, immunotherapeutic purposes and evaluation of therapies.
Intraosseous benign notochordal cell tumours: overlooked precursors of classic chordomas?
Authors: Yamaguchi T , Suzuki S , Ishiiwa H , Ueda Y
Published: December 2004

Aims:  Intraosseous benign notochordal cell tumour is a recently recognized condition that may undergo malignant transformation to classic chordoma. The aim of this study was to describe its clinicopathological characteristics.

Methods and results:  One hundred vertebral columns from atlas to coccyx and 61 pieces of the clival portion of the skull base, which were dissected from 100 autopsy cases, were examined microscopically. Twenty‐six intraosseous benign notochordal cell tumours were found in 20 cases. The patient group consisted of 15 males and five females with a mean age of 63 years. The results, according to anatomical segments, showed that 11.5% of the clivus, 5.0% of the cervical vertebrae, 0% of the thoracic vertebrae, 2.0% of the lumbar vertebrae, and 12.0% of the sacro‐coccygeal vertebrae were affected. Microscopic examination revealed well demarcated but unencapsulated sheets of bland physaliphorous cells mimicking adipocytes. The lesions lacked any intercellular myxoid matrix. The affected bone trabeculae were characteristically sclerotic.

Conclusions:  The study indicated a surprisingly high incidence of intraosseous benign notochordal cell tumours. The anatomical distribution of the tumours was identical to that of classic chordomas. The results support other evidence that classic chordomas develop from intraosseous benign notochordal cell tumours.
Expression of COX‐2 is increased with age in papillary thyroid cancer
Authors: Siironen P , Ristimäki A , Nordling S , Louhimo J , Haapiainen R , Haglund C
Published: December 2004

Aims: To study cyclooxygenase‐2 (COX‐2) and matrix metalloproteinase‐2 (MMP‐2) expression in papillary thyroid cancer (PTC). Expression of COX‐2 is elevated in various human tumours and it has an important role in carcinogenesis. MMP‐2 is also an important component of the metastatic potential of tumours. In PTC the most important factor affecting survival is age, but it is poorly understood why older PTC patients have a worse prognosis.

Methods and results: This retrospective study comprised 108 patients with PTC, and we compared patients who were either younger than 35 (n = 59) or older than 55 (n = 49). Paraffin‐embedded tumour samples were analysed for COX‐2 and MMP‐2 protein expression using immunohistochemistry. High (scores 2–3) COX‐2 immunostaining was observed in 38/108 (35%) of the tumours, and COX‐2 expression was significantly (P = 0.002) higher in the older age group (25/49; 51%) than in the young one (13/59; 22%).

Conclusions: Our study shows that COX‐2 expression increases with age. It is possible that the age‐related increase in COX‐2 expression could explain the more aggressive behaviour of PTC in the older age group compared with the young one.
Low‐grade fibromyxoid sarcoma versus low‐grade myxofibrosarcoma in the extremities and trunk. A comparison of clinicopathological and immunohistochemical features
Authors: Oda Y , Takahira T , Kawaguchi K , Yamamoto H , Tamiya S , Matsuda S , Tanaka K , Iwamoto Y , Tsuneyoshi M
Published: December 2004

Aims:  Low‐grade fibromyxoid sarcoma (LGFMS) is a distinctive variant of fibrosarcoma and has been reported to have metastatic potential despite its low‐grade histological findings. Low‐grade myxofibrosarcoma (MFS) is an important differential diagnosis of LGMFS, because it shows different biological behaviour. Of 75 MFSs in the extremities and trunk, we defined 22 grade 1 tumours as low‐grade MFS according to the French Federation of Cancer Centres grading system and compared the clinicopathological factors and immunohistochemical expression of cell cycle regulators with those of 11 LGFMSs.

Methods and results:  The two entities could be distinguished on histological grounds. Low‐grade MFS was characterized by the presence of prominent elongated, curvilinear capillaries and pseudolipoblasts, accompanied by an abundant myxoid matrix. It had no extensive solid areas. LGFMS was composed of bland spindle cells arranged in a whorled pattern with alternating myxoid and fibrous stroma. Curvilinear capillaries were not prominent and cytological atypia was absent. No tumour necrosis was observed in any of the 11 LGFMSs, whereas only one case showed tumour necrosis in less than 50% of the tumour in 22 low‐grade MFSs. The patients with low‐grade MFS were significantly older than those with LGFMS (low‐grade MFS average, 60.1 years; LGFMS average, 31.5 years; P < 0.0001) and low‐grade MFS occurred more frequently in a superficial location (low‐grade MFS 14/20; LGFMS 2/11; P = 0.0077). As for cell cycle regulator expression, the MIB‐1 labelling index (LI) (14.76 on average) and cyclin E LI (11.55 on average) in low‐grade MFS were significantly higher than those (MIB‐1 LI, 4.68 on average; cyclin E LI, 3.38 on average) of LGFMS, while p21 LI (25.53 on average) and p27 LI (42.68 on average) in low‐grade MFS were significantly lower than those (p21 LI, 42.74 on average; p27 LI, 57.28 on average) of LGFMS.

Conclusions:  We conclude that low‐grade MFS and LGFMS are distinctly different clinicopathological entities and the assessment of the immunohistochemical expression of MIB‐1, cyclin E, p21 and p27 as well as conventional clinicopathological features may be helpful to distinguish low‐grade MFS from LGFMS.