bluuebunny/crossref_metadata_2025 huggingface dataset:
Cesarean section rate: The effect of age and parity
Authors: Qublan Hussein , Alghoweri Ahmad , Al‐Taani Mohammad , Abu‐Khait Sami , Abu‐Salem Areej , Merhej Ahmad
Published: March 2003

Objective: To determine the impact of age and parity on Cesarean section rate.

Methods: Between 1 January 1998 and 31 December 1998, 7671 women delivered in two Jordanian

military hospitals (Prince Rhashed Hospital (PRH) and Prince Zaid Hospital (PZH)).

A total of 717 Cesarean sections were performed during the same period. Patients

who underwent Cesarean section were divided into three age groups: (i) <25 years

(n = 140); (ii) 25–35 years (n = 231); and (iii) >35 years

(n = 346). In addition, these patients were divided into five parity (P) groups:

(i) P0 (n = 85); (ii) P1 (n = 68); (iii) P2 (n = 83); (iv) P3

(n = 106); and (v) >P3 (n = 375). Information abstracted included maternal characteristics and indications for Cesarean section. Statistical analyses were performed using Pearson’s Chi‐squared test to evaluate the association between age, parity and Cesarean section.

Results: Of 7671 deliveries conducted during the study period, 717 Cesarean sections were

performed, giving an incidence of 9.3%. The Cesarean section rate in the

<25, 25–35 and >35 years age groups was 5.2, 6.9, and 20.9%,

respectively. The Cesarean section rate in the P0–>P3 parity groups was

8.5, 7.1, 7.4, 6.3 and 12.9%, respectively. According to the indications,

a statistically significant increase in Cesarean section rates with increasing maternal

age and parity (P < 0.05 and P < 0.01, respectively) was observed.

Conclusion: The Cesarean section rate was positively influenced by increasing maternal age and parity.
Anti‐E alloimmunization in pregnancy: Management dilemmas
Authors: To William W.K. , Ho San‐Ni , Mok Ka Ming
Published: March 2003

Compared to anti‐D alloimmunization, anti‐E alloimmunization is a less common cause of hemolytic diseases of the newborn. Being a less potent immunogen, clinical manifestations of anti‐E alloimmunization are more variable and usually of less severity. However, the clinical obstetric management of these cases of anti‐E alloimmunization is just as challenging. We report here the management of a patient with anti‐E alloimmunization to illustrate the controversies of invasive and non‐invasive monitoring in the management of such cases.
Person‐centred care for people with dementia: a quality audit approach
Authors: Martin G. W. , Younger D.
Published: March 2003

This paper addresses the concept of person‐centred care for people with dementia by consideration of an audit process using dementia care mapping as the audit tool. It is argued that this tool is best for identifying the lived experiences of the people in receipt of care. As a result it is able to identify the overall culture of care and its level of ‘person‐centred’ approach. The audit was conducted on 12 units, half of which were day units and the others catering for inpatients. Five patients were mapped on each day for a 4‐day period. The results give some idea of the quality of care and identify where improvement is necessary. Scores such as well‐being values and the Dementia Care Index give clear signposts to the level of person‐centred care and highlight where staff development is necessary. Recommendations are given to aid on‐going planning.
Murine pharmacokinetics and metabolism of oleandrin, a cytotoxic component of Nerium oleander
Authors: Ni Dan , Madden Timothy L. , Johansen Mary , Felix Edward , Ho Dah H. , Newman Robert A.
Published: March 2003

Pharmacokinetic studies of [3H]oleandrin, a cardiac glycoside component of Anvirzel™, were conducted in mice after either an i.v. dose (40 μg/kg) or a p.o. dose (80 μg/kg). Oleandrin was rapidly absorbed after oral dosing (Cmax at 20 min) although the elimination half‐life was longer (2.3 ± 0.5 h) than that after i.v. dosing (0.4 ± 0.1 h). The AUC0–∞ values obtained after i.v. and p.o. dosing were 24.6 ± 11.1 and 14.4 ± 4.3 (ng · h/ml), respectively, resulting in an oral bioavailability of approximately 30%. After i.v. administration, oleandrin concentration in liver was approximately twice that measured in heart or kidney tissue. Oleandrigenin, the aglycone of oleandrin, was also found in these tissues. At 5 min, >60% of the total radioactivity in liver was due to oleandrin while 28% of the given dose was present as oleandrigenin. Twenty‐four hours following injection, 8% of total radioactivity was excreted in urine and contained both oleandrigenin (4.4% of the injected dose) and oleandrin (1.9%). Sixty‐six percent of injected radioactivity was found in feces and consisted of oleandrin and oleandrigenin in equal amounts. Uptake of oleandrin in brain after i.p. injection of oleandrin (3 mg/kg) or oleander extract (700 mg/kg) was examined. Measured by LC/MS/MS, oleandrin content in brain was higher following injection of extract than it was with an equivalent dose of oleandrin. The data suggest that components within oleander extract may enhance transport of oleandrin across the blood brain barrier.
Infection structures of biotrophic and hemibiotrophic fungal plant pathogens
Authors: Perfect Sarah E. , Green Jonathan R.
Published: March 2003

Biotrophic plant pathogenic fungi are one of the major causes of crop losses. The infection processes they exhibit are typified by infected host plant cells remaining alive for several days. This requires the development of specialized infection structures such as haustoria which are produced by obligate biotrophs, and intracellular hyphae which are produced by many hemibiotrophs. These infection hyphae are surrounded by the host plant plasma membrane, and in the case of haustoria the extrahaustorial membrane differs biochemically and structurally from the normal membrane. An interfacial matrix separates haustoria and intracellular hyphae from the invaginated membrane and this seems to be characteristic of biotrophic interactions. There is clear evidence for molecular differentiation of the haustorial plasma membrane in powdery mildews and rusts in comparison with the other fungal membranes. Relatively few pathogenicity genes related to biotrophy, and the switch from biotrophy to necrotrophy in hemibiotrophs, have been identified.
Sugar‐beet powdery mildew (Erysiphe betae)
Authors: Francis Sally
Published: March 2003

Erysiphe betae causes sugar‐beet powdery mildew, a serious fungal foliar disease resulting in sugar yield losses of up to 30%. The fungus occurs world‐wide in all regions where sugar beet is grown and it also infects other edible beet crops, e.g. beetroots (garden beets). Unlike other powdery mildews, E. betae has so far received relatively little attention from pathologists and the precise mechanisms by which it infects its host remain unclear. Sources of genetic resistance have been identified in cultivated and wild Beta germplasm and molecular markers developed linked to Pm, the only single major R gene described so far, and also to QTL.

Taxonomy:  Erysiphe betae (Vañha) Weltz.—Kingdom Fungi, Subdivision Ascomycotina, Class Pyrenomycetes, Order Erysiphales, Family Erysiphaceae, Genus Erysiphe.

Identification:  Superficial persistent mycelium; unbranched erect conidiophores; conidia ripen singly, are hyaline, ovoid, 30–50 µm × 15–20 µm; cleistothecia globose, dark brown/black, 80–120 µm in diameter; mostly 4–8 asci per cleistothecium, mostly 2 or 3 spores per ascus.

Host range:  A monophagous parasite specific to Beta species.

Disease symptoms:  Infected foliage and inflorescences bear numerous powdery, white colonies. Under favourable environmental conditions the colonies coalesce, host tissue develops chlorosis and usually senesces early. Cleistothecia develop on heavily infected leaves in late summer and are small black/dark brown globose bodies resting on the mycelial surface.

Control:  Chemical control and partial genetic resistance.
Isolation of infection‐specific sequence tags expressed during early stages of maize anthracnose disease development
Authors: Sugui Janyce A. , Deising Holger B.
Published: March 2003

Thirteen infection‐specifically expressed sequence tags (ESTs) corresponding to genes activated during early stages of the interaction between the hemibiotrophic fungus and causal agent of anthracnose Colletotrichum graminicola, and its host, Zea mays, have been cloned. Six fungal ESTs appear to have a function in reprogramming the protein pattern and/or fungal infection structure differentiation and three plant ESTs seem to be involved in pathogen recognition and mediation of defense responses. Four ESTs share no similarity with known sequences in the database and may thus represent hitherto unknown genes that play a role in the C. graminicola—maize interaction. This report adds to the understanding of early stages of the infection, i.e. the biotrophic and beginning necrotrophic phase of disease development, and provides the basis for future functional gene analyses.
Hydrophobins and the interactions between fungi and plants
Authors: Whiteford James R. , Spanu Pietro D.
Published: March 2003

Hydrophobins are small proteins thought to be ubiquitous in filamentous fungi. They are usually secreted and are found on the outer surfaces of cell walls of hyphae and conidia where they mediate interactions between the fungus and the environment. We review here what is currently known about the primary and secondary structure of these proteins, as well as their post‐translational modifications. We also discuss the diverse functions of hydrophobins in biology and development, with particular attention to fungi involved in pathogenesis and symbiosis.
Applications of recombinant antibodies in plant pathology
Authors: Ziegler Angelika , Torrance Lesley
Published: March 2003

Advances in molecular biology have made it possible to produce antibody fragments comprising the binding domains of antibody molecules in diverse heterologous systems, such asEscherichia coli, insect cells, or plants. Antibody fragments specific for a wide range of antigens, including plant pathogens, have been obtained by cloning V‐genes from lymphoid tissue, or by selection from large naive phage display libraries, thus avoiding the need for immunization. The antibody fragments have been expressed as fusion proteins to create different functional molecules, and fully recombinant assays have been devised to detect plant viruses. The defined binding properties and unlimited cheap supply of antibody fusion proteins make them useful components of standardized immunoassays. The expression of antibody fragments in plants was shown to confer resistance to several plant pathogens. However, the antibodies usually only slowed the progress of infection and durable ‘plantibody’ resistance has yet to be demonstrated. In future, it is anticipated that antibody fragments from large libraries will be essential tools in high‐throughput approaches to post‐genomics research, such as the assignment of gene function, characterization of spatio‐temporal patterns of protein expression, and elucidation of protein–protein interactions.
Differential roles of geminivirus Rep and AC4 (C4) in the induction of necrosis in Nicotiana benthamiana
Authors: Van Wezel Rene , Dong Xiangli , Blake Patrick , Stanley John , Hong Yiguo
Published: March 2003

The replication‐associated protein (Rep) of two distinct begomoviruses, the bipartite African cassava mosaic virus (ACMV) and the monopartite Tomato yellow leaf curl virus‐China (TYLCV‐C), elicits a reaction resembling a hypersensitive response (HR), associated with the induction of local necrosis and a systemic burst of hydrogen peroxide production, when expressed from a potato virus X vector in Nicotiana benthamiana. Transient expression of the ACMV Rep after Agrobacterium infiltration of N. benthamiana also triggered an HR‐like response. We have identified a region of the ACMV Rep, referred to as the HR‐like determinant domain (HRD, amino acids 119–179) that is essential for induction of the phenotype. Two additional regions have been identified (amino acids 1–85 and 86–118) that have various effects on the Rep‐mediated phenotype, suggesting that structural constraints are imposed on the functional HRD. The co‐expression of Rep with either AC4 or C4, expressed from overlapping open reading frames, triggers systemic necrosis in infected‐tissues, but AC4 or C4 alone is neither an inducer nor enhancer of the HR‐like phenotype. We propose that ACMV AC4 and TYLCV‐C C4 may counter the plant defence mechanism that is initiated by the Rep‐mediated local HR‐like phenotype.
Alfalfa mosaic virus: coat protein‐dependent initiation of infection
Authors: Bol John F.
Published: March 2003

Taxonomy:  Alfalfa mosaic virus
(AMV) is the type species of the genus
Alfamovirus
and belongs to the family
Bromoviridae. In this family, the tripartite RNA genomes of bromo‐, cucumo‐ and probably oleaviruses are infectious as such, whereas infection with the three genomic RNAs of alfamo‐ and ilarviruses requires addition to the inoculum of a few molecules of coat protein (CP) per RNA molecule. RNAs 1 and 2 encode the replicase proteins P1 and P2, RNA 3 encodes the movement protein and CP. CP is translated from the subgenomic RNA 4.

 Physical properties:  RNAs 1 (3.65 kb), 2 (2.6 kb) and 3 (2.2 kb) are separately encapsidated into bacilliform particles which are 19 nm wide and 35–56 nm long. In addition, the virus preparations contain spheroidal particles each containing two copies of RNA 4 (0.88 kb). Virus particles contain 16–17% RNA and are mainly stabilized by protein–RNA interactions. The 3′‐termini of the viral RNAs contain a homologous sequence of 145 nucleotides that can adopt two alternative conformations: one represents a high‐affinity binding site for CP, the other resembles a tRNA‐like structure and is required for minus‐strand promoter activity.

 Hosts:  AMV mostly infects herbaceous plants, but several woody species are included in the natural host range. The experimental and natural host ranges include over 600 species in 70 families. At least 15 aphid species are known to transmit the virus in the stylet‐borne or non‐persistent manner.

 Economic importance:  AMV is a significant pathogen in alfalfa and sweet clover and can spread from these forages to neighbouring crops like pepper, tobacco or soybean. The recent introduction of the soybean aphid (Aphis glycines) in the mid‐west states of the USA has increased the incidence of AMV in soybean. AMV occurs world‐wide in potato and is referred to as ‘calico mosaic’ because of its characteristic symptoms on the foliage. However, the economic importance of AMV in potato is limited.

 Useful websites:   review paper;

 host range and physical properties;  structural information.
Milk ingredients as nutraceuticals
Authors: Steijns Jan M
Published: March 2003

Cow’s milk is considered as a basic food in many diets, and is rich in a variety of essential nutrients. With today’s sophisticated analytical, biochemical and cell‐biological research tools, the presence of many other (minor) compounds with biological activity has been demonstrated. Achievements in separation techniques in the dairy industry and enzyme technology offer opportunities to isolate, concentrate or modify these compounds, so that their application in functional foods, dietary supplements, nutraceuticals and medical foods has become possible.

Within the sequence of amino acids of a dietary protein, specific peptides may be located with specific biological activity. Peptides from casein may be used to enhance the solubility of minerals such as calcium and zinc—and hence increase the bioavailability of these minerals—or to reduce the activity of the angiotensin‐converting enzyme, which is involved in vasoconstriction and (hence) blood pressure.

Immunoglobulins from vaccinated cows may be considered as natural antimicrobials with certain advantages over synthetic antibiotics. Lactoferrin is an example of a minor milk protein that has been studied in great detail: it is becoming increasingly clear that it is important for the nonspecific defence against bacteria, fungi and viruses. Oligosaccharides, glycolipids and glycoproteins containing sialic acid residues may have a role as anti‐infectives.

Components such as growth factors may also be considered for future product development, because of the economies of scale used in the dairy industry.
Ultra Whey 99: a whey protein isolate case study
Authors: Neville J R , Armstrong K J , Price J
Published: March 2003

A case history of the manufacture and use of whey protein isolate is presented and particular attention is paid to the nutritional and processing characteristics of Ultra Whey 99, a whey protein isolate manufactured by Volac International Ltd. The growth of the nutritional bar market in the USA is used to demonstrate the increasing demand for specialist products such as whey protein.
The NHS R&D Information Systems Strategy (ISS)
Authors: ENNIS J. , COOPER A. , HENSHALL C. , JACQUES J. , ZAMAN N.
Published: March 2003

Following a strategy study which reported in August 1992 the NHS R&D Information Systems Strategy (ISS), a strategic framework for information systems, has been developed to support research and development in the NHS. This paper summarizes its main features, illustrates the benefits which specific information systems will bring, and outlines how the products of the progamme are disseminated and accessed.
The quality and impact of MEDLINE searches performed by end users
Authors: MCKIBBON K.A. , WALKER‐DILKS C.J.
Published: March 2003

Evidence suggests that MEDLINE is becoming an important clinical tool that can improve the care and health of patients. Efforts to improve the quality and impact of end‐user searching are needed and ongoing. End users are completing many MEDLINE searches. They appreciate and value training along with feedback on their searching techniques. Practice is, however, the biggest single factor in improving the quality of searching. Key roles for the library in end‐user searching include, providing the most effective MEDLINE access possible to the maximum number of users, and providing training that includes feedback and practice opportunities. System‐wide advances in structured abstracts, indexing, system design, informatics research and the literature itself will make searching easier and more effective in the future. More important than the quality of search results per se is the impact that end‐user searches have on patient care and patient outcomes. Growing evidence shows that both patient care and patient outcomes are improved by end‐user searches.
The efficiency of searches for randomized controlled trials in the International Journal of Eating Disorders: a comparison of handsearching, EMBASE and PsycLIT
Authors: HAY PHILLIPA J. , ADAMS CLIVE E. , LEFEBVRE CAROL
Published: March 2003

Our aims were: (i) to identify all reports of randomized controlled trials (RCTs) in the International Journal of Eating Disorders, (ii) to assess the number of these that were available in EMBASE and PsycLIT, and (iii) to investigate the precision of search strategies, designed for 100% sensitivity, for each of the above databases. The International Journal of Eating Disorders was handsearched for reports of RCTs. The 40 reports identified were then sought in EMBASE and PsycLIT. These records were assessed to identify methodological words/phrases which could be used to develop search strategies capable of identifying all reports of RCTs in the Journal. The precision of these searches was calculated. EMBASE contained 35 (88%) trials, and PsycLIT only 27 (68%). The 100% sensitive EMBASE strategy, designed to find all of the 35 trials, using methodological indexing text terms, identified 391 reports, and the 100% sensitive PsycLIT strategy identified 289 reports. The precision, therefore, of both searches was poor. Search strategies designed for high sensitivity resulted in very poor precision. A significant proportion of reports of RCTs were not indexed in PsycLIT.
Selection of library services by post‐registration nursing, midwifery and health visiting students
Authors: YEOH JEAN , MORRISSEY CLAIRE
Published: March 2003

This paper describes a small‐scale survey undertaken with 300 nurses, midwives and health visitors on post‐registration courses and registered for the ENB Higher Award. The aim was threefold: first to examine reasons for electing to use particular libraries; second, the relationship between workplace, home, teaching site and choice of library services; and third, the use of library enquiry services. There was a 56% response rate to the postal questionnaire and results indicated that the key factor in selecting a library was availability of resources rather than convenience to home or workplace. The third largest group of respondents worked in community organizations with little or no on‐site access to resources and were dependent on access to other libraries. Most who used the library for literature searching needed to seek help in spite of preliminary user education sessions. Similar levels of assistance were needed to locate journals and use the computerized book catalogue. The paper recommends explicit information on strategic entry points, necessity of a broad central collection, integration of information retrieval into post‐registration courses, use of self‐study packs, better trust/university liaison and recognition of the need for resource transfer from teaching to learning.
Postgraduate training in Public Health Medicine: St George's Hospital Medical School Library Public Health Information Service
Authors: Rook Rosemary , Adshead Fiona
Published: March 2003

This article examines the development of the St George's Hospital Medical School Library public health information service. Begun in 1997 as a pilot project to support Public Health Specialist Registrars in South Thames West, it is now an established part of postgraduate training in the region.

An outline of the service is described, including the evolution of the post of Public Health Librarian. Issues influencing the development of the service, and the establishment of the Librarian as part of the public health network are discussed.

This is a transferable model of public health information provision, which as a centralized resource makes best use of available funding. As a LIS model it is an effective and efficient way of maximizing resources, and delivering a service to a specialist user group that is spread across a wide geographical area.
The focus group: a tool for programme planning, assessment and decision‐making—an American view*
Authors: Glitz Beryl , Hamasu Claire , Sandstrom Heidi
Published: March 2003

The objective of this paper is to describe the focus group process used with hospital librarians in the National Network of Libraries of Medicine, Pacific Southwest Region (NN/LM/PSR), in order to illustrate how focus groups can be effectively used in the library setting to plan programmes around identified needs.

This paper explores the focus group methodology, a qualitative research technique, by discussing why it is used and the process involved in its use. Aspects of the methodology that are discussed include participant selection, question development, data analysis, and use of results in programme planning.

The focus group findings assisted NN/LM/PSR in understanding the needs of hospital librarians related to integrating electronic resources into library services. The focus group data were used to determine the forum, content and speakers for a day‐long symposium and subsequent planning meeting.

The use of the focus group technique to assess the needs of a specific group on a specific issue resulted in activities and programmes that met these needs successfully. Based on the experiences detailed in this paper, the authors are confident that focus groups are an effective tool for programme planning, needs assessment and decision‐making for all types of libraries.
A controlled vocabulary for nursing and allied health in Norway*
Authors: Flor Patricia , Jakobsson Arne , Mogset Ingrid , Taylor Solveig , Aasen Sigrun Espelien
Published: March 2003

Nursing and allied health libraries at educational institutions in Norway have generally indexed their book collections with uncontrolled terms. With the reorganization of higher education in 1994, the majority of these libraries joined BIBSYS, which is a joint library system for higher education and research in Norway. This has led to chaos when searching the joint catalogue for literature on nursing and related fields. A term such as ‘behaviour problems’ may have up to five synonyms.

 In an attempt to improve the quality of searching the health literature, BIBSYS appointed a working group in the Spring of 1999 to find a suitable controlled vocabulary for this subject area, and to see how this vocabulary could be integrated into BIBSYS. The group presented its recommendations in October 1999. The report has been well received by the BIBSYS Board and by user groups.

 There are no Norwegian vocabularies that are suitable for use in nursing and allied health, therefore it will be necessary to translate and combine existing thesauri. The group has looked at the Nordic Multilingual Thesaurus on Health Promotion, the Swedish Spriline Thesaurus, MeSH (Medical Subject Headings) and cinahl Subject Heading List. Other relevant thesauri are AMED/CATS Thesaurus, Bioethics Thesaurus (Bioethicsline) and the RCN thesaurus.

The group recommends the development of a Norwegian thesaurus based on a translation of parts of MeSH and cinahl Subject Heading List.
Comparison of immunohistochemical staining of the novel antibody melan‐A with S100 protein and HMB‐45 in malignant melanoma and melanoma variants
Authors: Blessing  , Sanders  , Grant
Published: March 2003

Aims:

The staining pattern of the recently described antibody melan‐A was compared with those of S100 protein and HMB‐45 in a variety of melanocytic lesions to assess the specificity and sensitivity of these antibodies.

Methods and results:

Immunohistochemical staining of paraffin sections of a range of melanocytic lesions was carried out following a high temperature antigen retrieval technique. The pattern and intensity of staining was semiquantitatively scored. S100 remains the most sensitive marker of melanocytic differentiation being diffusely positive in all benign and all primary and secondary malignant lesions including naevoid melanomas, and in most desmoplastic/spindle cell melanomas. Of the two more specific melanocytic markers melan‐A stains the majority of benign and malignant lesions diffusely but with occasional patchy positivity only in some secondary melanoma deposits and with little staining of desmoplastic/spindle cell melanomas. HMB‐45 is the least sensitive of the three showing little positivity of benign mature naevus cells, only variable patchy positivity of primary and secondary melanoma cells and limited positivity in naevoid, desmoplastic and metastatic melanomas.

Conclusions:

Melan‐A is a useful addition to antibody panels as it is apparently specific for melanocytic lesions and is more sensitive than HMB‐45; however, it has less value than S100 in the detection of spindle cell and desmoplastic melanomas.
Pulmonary giant cell carcinoma: pathological entity or morphological phenotype?
Authors: Attanoos  , Papagiannis  , Suttinont  , Goddard  , Papotti  , Gibbs
Published: March 2003

Aims:

To evaluate the morphological spectrum and clinical significance of giant cell carcinoma and to assess the frequency of tumour giant cell production in a consecutive series of primary (non‐giant cell) lung tumours.

Methods and results:

Forty‐six cases of giant cell carcinoma of the lung were collated from two centres over a 12‐year period. Giant cell carcinoma was found to be associated with areas of clear cell carcinoma, spindle cell carcinoma and showed trophoblastic differentiation (syncytiotrophoblastic giant cells and β‐human chorionic gonadotrophin immunopositivity) in 57%, 34% and 26% cases, respectively. ‘Pure’ giant cell carcinoma was identified in five (11%) cases. Eleven of the tumours contained diastase‐resistant periodic acid–Schiff positive material and were separately designated as giant cell adenocarcinomas. Areas of squamous cell and neuroendocrine differentiation (as determined by chromogranin A and Leu‐7 immunopositivity) were not found. The median survival for giant cell carcinoma (excluding the giant cell adenocarcinomas) was 18 months. Median survival was not adversely affected by the extent of tumour giant cell formation or by the presence of trophoblastic differentiation. Of 200 consecutive non‐small cell lung carcinomas, tumour giant cells constituting < 10% of the tumour were identified in 32% of adenocarcinomas and 26% of squamous cell carcinomas.

Conclusions:

The presence of tumour giant cells in lung carcinoma does not, in itself, indicate a more aggressive tumour type. Giant cell carcinoma of the lung does not appear to be a distinct entity but a morphological phenotype expressed by a heterogenous group of tumours. We support and advocate the use of an encompassing term such as ‘pleomorphic’ or ‘anaplastic’ carcinoma for those tumours showing no specific differentiation pattern but which express diverse morphological features such as giant cell formation, clear or spindle cell change.
Localization of the cellular expression of inhibin in trophoblastic tissue
Authors: Mccluggage  , Ashe  , Mcbride  , Maxwell  , Sloan
Published: March 2003

Aims:

Inhibin is a peptide hormone which is normally produced by ovarian granulosa cells and which inhibits the release of follicle stimulating hormone from the pituitary gland, thus acting as a modulator of folliculogenesis. Serum inhibin levels are higher during pregnancy than during the normal menstrual cycle and the placenta is thought to be a source of circulating inhibin. Previous studies have yielded conflicting results as to the cellular localization of inhibin in the placenta and the aim of the present study was to investigate the immunohistochemical localization of the hormone in placental tissue. We also wished to investigate whether inhibin could be demonstrated in choriocarcinoma and in non‐gestational trophoblastic tissue.

Materials and results:

Immunohistochemical staining was performed using a monoclonal antibody against the α subunit of human inhibin. Specimens included in the study were intrauterine products of conception (n = 36), extrauterine products of conception (n = 4), decidualized endometrium (n = 15), extrauterine decidualized tissue (n = 3), hydatidiform mole (n = 5), uterine choriocarinoma (n = 2) and testicular embryonal carcinoma with syncytiotrophoblast giant cells (n = 6). In cases of products of conception, including hydatidiform mole, there was consistent strong positive staining of syncytiotrophoblast but no staining of cytotrophoblast with anti‐inhibin. Staining with anti‐inhibin highlighted trophoblastic cells within the placental bed. In a small number of cases there was focal weak positive staining of decidua. There was positive staining of the two cases of uterine choriocarcinoma and of syncytiotrophoblast giant cells in the six cases of testicular embryonal carcinoma.

Conclusions:

The study shows that immunohistochemically detectable inhibin α subunit in placental tissue is mainly localized within syncytiotrophoblast although in some cases there is also positive staining of decidua. Production of inhibin by these cells may account for raised serum levels during pregnancy. Inhibin can also be demonstrated in choriocarcinoma and in non‐gestational trophoblastic tissue. Inhibin is a sensitive marker of syncytiotrophoblast and staining with this antibody may prove useful in the diagnosis of choriocarcinoma and in the demonstration of trophoblastic cells in germ cell tumours.
Liver biopsy is a useful predictor of response to interferon therapy in chronic hepatitis C
Authors: Kaserer  , Fiedler  , Steindl  , Müller  , Wrba  , Ferenci
Published: March 2003

Aim

To evaluate the usefulness of easily assessable morphological parameters in liver biopsies in order to predict efficacy of interferon‐α (IFN) treatment in patients with chronic hepatitis C.

Methods and results

Inflammatory activity and fibrosis (according to Scheuer), and the hepatic iron content (according to Rowe and DiBisceglie) were assessed in pre‐treatment liver biopsies of 73 de novo patients with chronic hepatitis C. Furthermore the presence of fat, lymphoid aggregates, and bile duct lesions was evaluated. With respect to IFN therapy patients were classified as responders alanine aminotransferase (ALT) normal and negative hepatitis C virus (HCV) RNA in serum at the end of treatment, n = 33) or non‐responders (n = 40). Non‐responders had more advanced fibrosis (P = 0.0001) and more extensive iron storage (P = 0.0008) than responders. In contrast absence of stainable iron was frequently (46%) associated with sustained response. Absence of fat droplets in hepatocytes was associated with response (P = 0.0001). Stepwise logistic regression analysis indicated that the stage of fibrosis, the hepatic iron grade, and the presence or absence of fat were independent predictors of response.

Conclusions

Liver biopsy provides useful information for selection of patients with hepatitis C for IFN therapy.
Loss of bcl‐2 expression in ductal carcinoma in situ of the breast relates to poor histological differentiation and to expression of p53 and c‐erbB‐2 proteins
Authors: Quinn  , Ostrowski  , Harkins  , Rice  , Loney
Published: March 2003

Aim: This study (1) investigates the incidence of bcl‐2 protein expression in a series of 108 cases of ductal carcinoma in situ (DCIS), including 25 with early invasive carcinoma, and (2) evaluates the relationship of bcl‐2 expression to the histological grade of DCIS and to the expression of oestrogen receptor (ER), c‐erbB‐2 and p53 proteins.

Methods and results

The expression of bcl‐2, oestrogen receptor (ER), c‐erbB‐2 and p53 proteins was determined immunohistochemically. Cases were regarded as positive for individual antibodies when at least 10% of the DCIS cells showed positive staining. DCIS was graded histologically as well (n = 9), intermediately (n = 24), or poorly differentiated (n = 75). bcl‐2 expression was documented in 57 cases (53%) and was strongly associated with the histological grade of DCIS (P < 0.0001). All cases of well‐differentiated DCIS were bcl‐2 positive and loss of bcl‐2 expression was almost exclusively confined to poorly differentiated DCIS lesions. bcl‐2 expression was also closely associated with positive ER status (P < 0.0001). Forty‐seven of 57 (82%) bcl‐2 positive cases were ER positive while 49/51 (96%) bcl‐2 negative cases were ER negative. There was a significant inverse correlation between bcl‐2 expression and both p53 protein expression (P = 0.0004) and c‐erbB‐2 expression (P < 0.0001). Nineteen of 24 (79%) p53 positive cases and 38/45 (84%) c‐erbB‐2 positive cases showed loss of bcl‐2.

Conclusions

Loss of bcl‐2 expression occurs in poorly differentiated DCIS and is related to negative ER status and to positive p53 and c‐erbB‐2 status. This pattern of bcl‐2 expression and its association with other biological markers in DCIS is similar to that reported in invasive breast carcinoma.
Hep Par 1 and selected antibodies in the immunohistological distinction of hepatocellular carcinoma from cholangiocarcinoma, combined tumours and metastatic carcinoma
Authors: S‐Y Leong A , Sormunen R T , Tsui W M S , Liew C T
Published: March 2003

Aims

To examine the usefulness of Hep Par 1 together with selected antibodies in the separation of hepatocellular carcinoma (HCC) from cholangiocarcinoma (CC), combined tumours (HCC‐CC) and metastatic carcinoma.

Methods and results

Antibodies to Hep Par 1, CK19, CK20 and factor XIIIa were applied to 32 HCCs, 27 CCs, five HCC‐CCs and 19 metastatic carcinomas from a variety of sites. Hep Par 1 produced distinctive granular staining of all benign hepatocytes and stained 30 HCCs in a heterogeneous manner, irrespective of the degree of differentiation. While labelling all cases of combined HCC‐CC, the antibody also stained the mucus‐secreting cells of four cases of pure CC. Anti‐CK19 produced distinctive staining of bile ducts and CC but also decorated four HCCs and 10 metastatic tumours. Factor XIIIa was not found in normal, reactive or neoplastic hepatocytes. CK20 was found in some cases of HCC and CC and in all cases of metastatic carcinomas from the colon.

Conclusions

Hep Par 1 was a sensitive marker of hepatocytes but its variable staining in HCC may produce false negative results in small biopsies and it was occasionally found in CC. The highest diagnostic yield was obtained when anti‐Hep Par 1, CK19 and CK20 were used in a panel. Factor XIIIa staining has no role in the diagnosis of liver cancers.
Analysis of histopathological factors associated with prolonged survival of 10 years or more for patients with thick melanomas (> 5 mm)
Authors: Spatz A , Shaw H M , Crotty K A , Thompson J F , McCarthy S W
Published: March 2003

Aims

Although tumour thickness is the best predictor of melanoma prognosis in patients with localized cutaneous melanoma, prolonged survival occasionally occurs in patients with thick melanomas (> 5 mm). This study examined histological features which were associated with long‐term survival.

Methods and results

Forty‐two patients with thick, vertical growth phase melanomas surviving 10 years or more after diagnosis were matched by clinical stage of disease, sex, age and anatomical site of the primary lesion with 42 patients with similar characteristics who died from their disease within 3 years of diagnosis. Fourteen histological factors were assessed in both groups. Tumours with spindle cell and Spitz‐like cell populations and those with low mitotic activity were significantly more frequently observed in long‐term survivors. There was also a significant excess of melanomas exhibiting desmoplasia and those lacking vascular invasion in the long‐term survivors.

Conclusions

These findings suggest that it may be useful to modify the current cutaneous melanoma classification on the basis of unusual cytological characteristics (as discussed at the recent 4th World Conference on Melanoma).
Blastic NK‐cell lymphoma expressing terminal deoxynucleotidyl transferase with Homer–Wright type pseudorosettes formation
Authors: Ko  , Kim  , Ree
Published: March 2003

Aims: Rosette‐forming malignant lymphoma is very rare. We report a blastic NK‐cell lymphoma expressing terminal deoxynucleotidyl transferase (TdT) with formation of Homer–Wright type pseudorosettes.

Methods and results

An 18‐year‐old boy presented with an enlarged inguinal lymph node. Histologically, the nodal architecture of the lymph node was diffusely effaced by small to medium sized monomorphic blastoid lymphoid cells which frequently formed Homer–Wright type pseudorosettes. Immunophenotyping of the tumour using immunohistochemistry and flow cytometry revealed LCA+, CD4+, CD56+, CD43+, TdT+, CD2−, cCD3−, CD8−, CD7−, CD34− and TIA‐1−. DNA analysis revealed no gene rearrangement of TCR β and γ genes. In situ hybridization for EBER 1 & 2 was negative. No azurophilic granules were found in the Wright stain. Complete remission was achieved with six cycles of chemotherapy with the CHOP regimen. The disease recurred in the paranasal sinuses and bone marrow 2 years later.

Conclusions

Immunophenotypic and genotypic similarities of the present case to those of TdT‐negative blastic NK‐cell lymphoma suggest that these diseases might be categorized as one entity irrespective of expression of TdT.
Immunolocalization of BRCA1 protein in normal breast tissue and sporadic invasive ductal carcinomas: a correlation with other biological parameters
Authors: Lee  , Jin  , Chang  , Lin  , Su
Published: March 2003

Aim

BRCA1, a nuclear phosphoprotein, normally functions as a negative regulator of the cell cycle and may be an active inhibitor of neoplastic progression. Mutation of the BRCA1 gene has been demonstrated in 80% of familial breast cancer. Decreased mRNA levels or aberrant subcellular locations of BRCA1 have been identified in breast cancer lines and in sporadic cases of breast cancer tissues. The expression of BRCA1 in large series of variously differentiated breast carcinomas with correlation with other biological parameters has not been clarified.

Methods and results

The BRCA1 expression in normal breast tissue (n = 15) and in sporadic cases of invasive ductal carcinoma (n = 108) was determined using immunohistochemistry. BRCA1 expression was correlated with other prognostic parameters including p53, c‐erbB‐2, bcl‐2, oestrogen receptor (ER), histological grade, tumour size, axillary lymph node status and age. BRCA1 was exclusively (100%) localized in the nuclei of normal ductal and lobular epithelia. However, this nuclear expression pattern was variable in breast carcinoma (76.8%). Loss of nuclear BRCA1 expression (22 of 108 cases, 20.4%) correlated well with high histological grade (P < 0.025) and bcl‐2‐negative tumours (P < 0.05) and frequently in ER‐negative tumours.

Conclusion

BRCA1 nuclear expression could be considered to represent the normal or physiological phenotype. Complete loss of BRCA1 nuclear expression in breast cancer and its correlation with other poor prognostic markers suggest that BRCA1 expression may play an important role in the pathogenesis and prognosis of sporadic breast carcinoma. Altered BRCA1 phenotype may therefore provide an additional prognostic parameter for breast cancer.
Diversion colitis — new light through old windows
Authors: Edwards  , George  , Warren
Published: March 2003

Diversion proctocolitis is an iatrogenic disorder caused by surgical diversion of the faecal stream away from the colorectal mucosa. Such surgery may be necessary in cases of tumour, trauma or inflammatory conditions of the colorectum. Histopathological change is characterized by a chronic lymphoplasmacytic inflammatory infiltrate, and the hallmark feature, lymphoid follicular hyperplasia. Histological appearances are determined by the disease state of the colonic mucosa prior to faecal diversion. Macroscopic appearances may vary considerably, but often include aphthoid ulceration. The exact pathogenesis of the condition remains unclear, but the removal of short‐chain fatty acids, present in the faecal stream, is considered an important aetiological factor. Current research areas, including the microbiology and cellular kinetics of diversion colitis, are discussed along with clinical features and treatments.
Observer agreement on the grading of gastric atrophy
Authors: Offerhaus G J A , Price A B , Haot  , ten Kate F J W , Sipponen  , Fiocca  , Stolte  , Dixon M F
Published: March 2003

Aims

Assessment of lesser or doubtful degrees of gastric atrophy can be difficult, especially in the antrum, since well established criteria are lacking. At the Houston Working Party on Gastritis in 1994 a visual analogue scale was designed for the grading of histopathological parameters. This was done to promote uniformity in grading by acting as a reference. The purpose of the present study was to measure interobserver variation between pathologists familiar with the Houston visual analogue scale in a specifically selected set of biopsies from patients with lesser or doubtful degrees of atrophy.

Methods and results

Thirty cases with biopsies of the antrum and corpus from a long‐term follow‐up study on Helicobacter pylori gastritis comprised the current study material. The cases were selected from that study because there had been uncertainty or disagreement on the presence of gastric atrophy. The study set of haematoxylin and eosin (H & E) slides was circulated amongst gastrointestinal pathologists familiar with the visual analogue scale who were unaware of the source of the study set nor had any other clinical information. Interobserver variability was analysed using kappa statistics. The overall agreement for the grade of atrophy in antral biopsies was 0.461; the kappa value was 0.18 (95% confidence limits 0.12–0.24), which is considered poor agreement. The kappa value was nevertheless statistically significant (P < 0.01). The overall agreement on the grade of atrophy in the corpus biopsies was apparently good (0.833), but the kappa which adjusts for chance agreement was only moderate (0.48; 95% confidence limits 0.42–0.55; P < 0.001).

Conclusion

The studied series comprised a self‐selected sample in which there was doubt about the grade of atrophy and such a sample will produce lower kappa values than a random sample of gastric biopsies. The results nevertheless confirm that better guidelines and firm criteria are needed to properly diagnose and grade gastric atrophy. It is suggested that the use of two grades, low‐ and high‐grade atrophy, akin to that in use for grading inflammatory bowel disorder (IBD)‐ associated dysplasia, could improve agreement. Furthermore optimal biopsy quality with full thickness mucosa and proper orientation appears important for grading gastric atrophy.
Irreversible glomerular lesions induced by crystal precipitation in a renal transplant after foscarnet therapy for cytomegalovirus infection
Authors: Justrabo  , Zanetta  , Martin  , Assem  , Mousson  , Maurice‐Estepa  , Rifle  , Tanter
Published: March 2003

Aims

Foscarnet is an antiviral agent used to treat cytomegalovirus infection in AIDS patients and in transplant recipients. In most cases, foscarnet induces reversible tubulo‐interstitial lesions which can be avoided by correct hydration. We report the first case of crystal foscarnet precipitation within glomerular capillaries in a renal transplant.

Methods and results

The recipient, a 49‐year‐old man, developed a nephrotic syndrome with haematuria and an acute renal failure after foscarnet therapy for cytomegalovirus (CMV) infection. The polarization examination of the first graft biopsy revealed the presence of birefringent crystals within glomeruli and tubules. Infrared analysis attested to the presence of trisodium foscarnet salts and mixed sodium calcium salts coloured by Von Kossa’s reaction. A second biopsy showed glomerular sclerosis, interstitial fibrosis, tubular atrophy and crystal vanishing. Polymerase chain reaction (PCR) in situ applied to this biopsy confirmed the diagnosis of cytomegalovirus infection.

Conclusions

These adverse effects might be the result of a toxic synergy between foscarnet and other drugs. In cases with crystalline precipitation, graft biopsy remains the best mean of diagnosis and follow‐up of glomerular damage.
Loss of E‐cadherin expression in early gastric cancer
Authors: Blok  , Craanen  , Dekker  , Tytgat
Published: March 2003

Aims

Reduction or loss of E‐cadherin expression was examined in early gastric carcinomas and precursor lesions with the following aims: (1) to assess overall E‐cadherin expression in various stages of gastric carcinogenesis; (2) to correlate E‐cadherin expression with the Lauren type, the grade of differentiation and the type of growth pattern of the tumours; and (3) to correlate E‐cadherin expression with lymph node metastasis and overall prognosis.

Methods and results

Forty‐five paraffin‐embedded gastrectomy specimens from early carcinomas were examined for the presence of various precursor lesions. The Lauren type, the grade of differentiation and the type of growth pattern were reassessed for all early carcinomas. E‐cadherin expression was examined using antibody HECD‐1. Whereas E‐cadherin was strongly and evenly expressed in the gastric foveolar epithelium, intestinal metaplasia and early gastric carcinomas showed a lower expression. A significant difference in E‐cadherin expression was found between the Lauren types (P < 0.0001). Moreover, an inverse correlation was found between E‐cadherin expression and histological grade (P < 0.0001). Neither a difference in E‐cadherin expression between the various growth types nor an association with lymph node metastasis and overall prognosis was found.

Conclusions

The Lauren types differ in E‐cadherin expression, although reduced E‐cadherin expression in all probability rather reflects poor differentiation than a diffuse growth pattern ‘genotype’. Moreover, E‐cadherin expression does not underlie the difference in biological behaviour of early carcinomas with different types of growth pattern. Finally, E‐cadherin expression is not associated with lymph node status and 5‐year survival rate, at least not in early gastric carcinomas.