bluuebunny/crossref_metadata_2025 huggingface dataset:
The role of the urokinase‐type plasminogen activator (uPA) and its receptor (CD87) in lipodermatosclerosis
Authors: Herouy Yared , Aizpurua Jon , Stetter Christoph , Dichmann Stefan , Idzko Marco , Hofmann Clemens , Gitsch Gerald , Vanscheidt Wolfgang , Schöpf Erwin , Norgauer Johannes
Published: March 2003

Background: Lipodermatosclerosis refers to a sclerosing panniculitis and dermopathy of the lower extremities sometimes seen in association with venous ulceration. Matrix metalloproteinases are implicated in the pathogenesis of venous leg ulcers and the in vitro activation of recombinant MMP‐2 is controlled by the plasminogen activation system. To better understand the role of plasminogen activation in the pathogenesis of venous leg ulcers we investigated fibrinolytic factors and their inhibitors in tissue samples of lipodermatolsclerosis.

Methods: The expression and the functional state of the urokinase‐type plasminogen activator (uPA), the tissue‐type plasminogen activator (tPA), the urokinase receptor (CD87), the plasminogen activator inhibitors‐1 and ‐2 (PAI‐1 and PAI‐2) were assayed using reverse transcription polymerase chain reaction, Western blot, fibrin zymography and immunohistochemistry analyses in tissue samples of lipodermatosclerosis.

Results: Our results provide direct evidence of elevated expression of uPA (p<0.01) and CD87 (p<0.01) mRNA and protein level in lipodermatosclerosis in comparison with healthy skin. By immunohistochemistry, elevated expression of uPA and CD87 could be detected. Fibrin zymography showed significantly elevated endogenous uPA activity (p<0.01) in liposclerotic lesions compared to healthy controls.

Conclusion: Our findings indicate that elevated plasminogen activation in lipodermatosclerotic tissue may play a crucial role in the pathogenesis of venous leg ulceration.
Insights from the asebia mouse: a molecular sebaceous gland defect leading to cicatricial alopecia
Authors: Stenn K. S.
Published: March 2003

The primary cicatricial alopecias have proven to be challenging for the clinician, dermatopathologist and the researcher – let alone the patient. If we are to improve our diagnostic and therapeutic tools for these very difficult disorders, we will need greater insight into their etiology. Recent work with the mouse mutant, asebia, provides a model for cicatricial alopecia. In this model the pathology – perifollicular inflammation, sebaceous gland “destruction”, hair shaft granuloma, and cicatricial follicle drop‐out – results from the mutation of one very important sebaceous gland gene. In the absence of this gene, the sebaceous gland is hypoplastic and normal sebum production is minimal to absent. In this paper the relevance of this mutant to human alopecias is discussed and the point emphasized that the pathogenesis of some forms of human cicatricial alopecia could involve the sebaceous gland.
Expression of cutaneous lymphocyte‐associated antigen and TIA‐1 by lymphocytes in pityriasis lichenoides et varioliformis acuta and lymphomatoid papulosis: immunohistochemical study
Authors: Jang Kyoung‐Ae , Choi Jung‐Chul , Choi Jee‐Ho
Published: March 2003

Background: Pityriasis lichenoides et varioliformis acuta (PLEVA) and lymphomatoid papulosis (LyP) are benign self‐healing cutaneous eruptions that may be clinically and histologically similar. The purposes of this study were to evaluate immunohistological characteristics of PLEVA and LyP and to investigate whether Epstein‐Barr virus (EBV) may be present in PLEVA and LyP.

Methods: We performed an immunohistochemical staining in 12 cases of PLEVA and 8 cases of LyP using nine antibodies for CD3, CD4, CD8, CD30, CD45RO, CD56, CD79, cutaneous lymphocyte‐associated antigen (CLA), and TIA‐1. In situ hybridization was performed using fluorescein‐conjugated oligonucleotide probes for EBV early regions (EBER).

Results: In PLEVA, immunohistochemical studies revealed that infiltrated lymphocytes consisted of mainly CD3‐positive (5+), CD8‐positive (4+∼5+), CLA‐positive (4+∼5+) T cells and partly CD79 positive (+∼2+) B cells. CD4‐positive T cells were less than 25%. In LyP, immunohistochemical studies revealed that infiltrated lymphocytes consisted of partly CD3‐positive (5+), CD8‐positive (2+∼3+), CLA‐positive (3+∼4+) T cells and partly CD79‐positive (2+∼3+) B cells. CD4‐positive T cells were less than 10%. CD8 and CLA were more strongly expressed in PLEVA than in LyP. CD30 was strongly expressed in LyP but not expressed in PLEVA. CD79 was more expressed in LyP than in PLEVA. TIA‐1 was not expressed in any cases. In situ hybridization using antisense EBER probe showed negative reaction in all cases.

Conclusions: Immunohistochemical stains for CD8, CD30, CD79 and CLA may be valuable tools in the differential diagnosis between PLEVA and LyP. TIA‐1 was negative in LyP, which means cytotoxic cells may not be implicated in the pathogenesis of LyP. It was a contradictory result to the previous results. The absence of EBV in PLEVA and LyP suggests that this virus may not be operative in the pathogenesis of these diseases. These results suggest that LyP and PLEVA are separate disorders, thus accounting for their variable prognosis.
Primary giant cell tumor of soft tissue
Authors: Holst Valerie A. , Elenitsas Rosalie
Published: March 2003

Background: Primary giant cell tumor of soft tissue, also known as soft tissue giant cell tumor of low malignant potential, is a rare soft tissue tumor located in both superficial and deep soft tissue. Histologically, these lesions bear a close resemblance to their bony counterparts, giant cell tumor of bone, with round to spindle‐shaped cells intimately admixed with uniformly scattered osteoclast‐like multinucleated giant cells. In 1989 in the dermatology literature, two malignant giant cell tumors of soft parts were described that filled the dermis and extended into the subcutaneous tissue.

Methods: The authors report the rare occurrence of a giant cell tumor of soft tissue occurring primarily in the dermis that lacks overtly malignant features and clinically was thought to be an epidermal inclusion cyst.

Results: Light microscopy revealed a non‐encapsulated cellular dermal tumor containing numerous osteoclast‐like giant cells. Cytologic atypia was minimal and the mitotic count averaged 2–3/10 HPF. The histologic differential diagnosis is also discussed.

Conclusion: Giant cell tumor of soft tissue is a rare neoplasm of the skin, however, recognition of this tumor is important due to its behavior as a low‐grade malignancy.
Lichen striatus
Authors: Zhang Yiqiu , McNutt N. Scott
Published: March 2003

Background: Lichen striatus (LS) is a papulosquamous disorder with a distinctive linear distribution. The linearity has been shown to correspond in many cases to the pattern of Blaschko’s lines. The etiology is unknown. LS can usually be identified by clinical history and histology of typical lesions. However, the histologic features are diverse and some have stated they are nonspecific.

Methods: In an effort to identify those characteristic features, we have reviewed the routine slides in 37 cases for their diagnostic criteria. Ten cases were studied further by immunohistochemistry.

Results: The patient’s ages ranged from 1.3 to 49 years with mean age of 17.5 years. A female‐to‐male ratio was 1.6 to 1. The lesions were predominantly distributed on the extremities in 26/34 cases. The consistent histologic features were: hyperkeratosis (29/37), parakeratosis (21/37) with a few necrotic keratinocytes (28/37) in the epidermis, mild spongiosis (29/37) with exocytosis of lymphocytes (33/37). The dermal infiltrate comprised mainly lymphocytes and macrophages. At the dermal‐epidermal junction, the infiltrate was either focal (20/37) or lichenoid (17/37) patterns. Superficial and deep perivascular lymphocytic inflammatory infiltrate was present in most of the cases (33/37). Appendageal involvement (34/37) was in hair follicles (24/37) or eccrine glands or ducts (22/37) or both (12/37). Satellite cell necrosis may be seen (11/37). Colloid bodies were present in 16/37 of the cases. Immunohistochemistry showed that most of the small lymphocytes in the upper dermis and epidermis were positive for CD7. Most of the lymphocytes in the epidermis were positive for CD8. CD1a Langerhans’ cells were either decreased (5/10) or increased (3/10) or normal (2/10) in the epidermis.

Conclusion: The histologic diagnosis of LS can be made on the basis of the combination of these histologic features in the appropriate clinical context. Multiple biopsies may be necessary to determine whether all of these features are present in a given case.
“Apocrine” poroma: review of the literature and case report
Authors: Kamiya Hideki , Oyama Zuiei , Kitajima Yasuo
Published: March 2003

Background: “Apocrine” poroma has recently been proposed as a new term to designate a distinctive benign skin neoplasm with differentiation toward the folliculosebaceous‐apocrine unit.

Case report: In support of alternative differentiation, a case of apocrine poroma is reported in a 73‐year‐old man. A nodule on the right upper abdomen, which was thought clinically to be seborrheic keratosis or basal cell epithelioma, was excised.

Histology: Histologically, this neoplasm heterogeniously consisted of poroma‐like, sebaceous and follicular epithelial components. Since these components share the common embryologic origin of the folliculosebaceous‐apocrine unit, this histologic pattern indicates apocrine differentiation of the tumor.

Conclusion: This is an additional case to support the term “apocrine” poroma as a diagnosis.
Scarring alopecia and the dermatopathologist
Authors: Sperling Leonard C.
Published: March 2003

Background: The evaluation of patients with cicatricial alopecia is particularly challenging, and dermatopathologists receive little training in the interpretation of scalp biopsy specimens. Accurate interpretation of specimens from patients with hair disease requires both qualitative (morphology of follicles, inflammation, fibrosis, etc.) and quantitative (size, number, follicular phase) information. Much of this data can only be obtained from transverse sections. In most cases, good clinical/pathologic correlation is required, and so clinicians should be expected to provide demographic information as well as a brief description of the pattern of hair loss and a clinical differential diagnosis.

Results: The criteria used to classify the various forms of cicatricial alopecia are relatively imprecise, and so classification is controversial and in a state of evolution. There are five fairly distinctive forms of cicatricial alopecia: 1) chronic, cutaneous lupus erythematosus (discoid LE); 2) lichen planopilaris; 3) dissecting cellulitis (perifolliculitis abscedens et suffodiens); 4) acne keloidalis; and 5) central, centrifugal scarring alopecia (follicular degeneration syndrome, folliculitis decalvans, pseudopelade). Not all patients with cicatricial alopecia can be confidently assigned to one of these five entities, and “cicatricial alopecia, unclassified” would be an appropriate label for such cases.

Conclusion: The histologic features of five forms of cicatricial alopecia are reviewed. Dermatopathologists can utilize a “checklist” to catalog the diagnostic features of scalp biopsy specimens. In many, but not all, cases the information thus acquired will “match” the clinical and histologic characteristics of a form of cicatricial alopecia. However, because of histologic and clinical overlap between the forms of cicatricial alopecia, a definitive diagnosis cannot always be rendered.
EMLA® cream‐induced irritant contact dermatitis
Authors: Dong Huiting , Kerl Helmut , Cerroni Lorenzo
Published: March 2003

Background:  The Eutectic Mixture of Local Anesthetics (EMLA® cream) is a topical anesthetic used for providing pain relief in patients undergoing superficial surgical procedures. Cutaneous side‐effects have been reported rarely.

Case Report:  We present a case of irritant contact dermatitis induced by EMLA® cream in a 6‐year‐old boy with Wiskott‐Aldrich syndrome. Our patient showed clinically a well circumscribed patch corresponding to the site of application of the topical anesthetic. Histopathology showed confluent necrosis of keratinocytes in the upper epidermis, a mixed inflammatory infiltrate with priminent neutrophils in the upper dermis, and focal signs of interface changes including basal cell vacuolization and subepidermal cleft formation.

Conclusions:  Graft‐vs.‐host‐disease (GVHD), necrolytic migratory erythema, dermatitis enteropathica and pellagra should be considered in the histopathologic differential diagnosis of acute contact dermatitis caused by EMLA®.
Human herpes virus‐like particles in pityriasis rosea lesions: an electron microscopy study
Authors: Drago F. , Malaguti F. , Ranieri E. , Losi E. , Rebora A.
Published: March 2003

Background: In a previous study we detected virions with electron microscopy features of human herpes viruses in the supernatant of cocultured mononuclear cells from patients with acute pityriasis rosea. Because of their morphology and of polymerase chain reaction studies, we ascribed them to human herpes virus 7.

Objective: To find such virions in the lesional skin of pityriasis rosea patients.

Methods: Skin speciments from lesions of 21 patients with acute pityriasis rosea were examined by elecron microscopy.

Results: In 15 (71%) patients, human herpes virus particles in various stages of morphogenesis were detected. Mature enveloped virions appeared as typical human herpes virus virions, measuring about 160–200 nm in diameter and containing an electrodense cylindrical core, a capsid, an envelope with typical spikes and a very distinct tegument layer between the capsid and the envelope. They were very similar to those we reported in the supernatant of co‐cultured circulating mononuclear cells from patients with pityriasis rosea.

Conclusion: Our results confirm our previous findings and provides further evidence of a viral etiology for pityriasis rosea.
Actin‐binding protein fascin expression in skin neoplasia
Authors: Goncharuk Viktor N. , Ross Jeffrey S. , Carlson J. Andrew
Published: March 2003

Background:  Fascin containing actin bundles provide mechanical support to cellular protrusions and stress fibers. In cancers, some malignant cells (e.g. subsets of breast and ovarian carcinomas) express fascin. In skin cancer, the role of fascin is unknown.

Methods:  Cases of 61 keratocytic neoplasms, 35 melanocytic neoplasms, nine extramammary Paget's disease (four with adenocarcinoma) and five sarcomas (angiosarcoma and atypical fibroxanthoma) were examined by immunohistochemistry, using monoclonal antihuman fascin antibody, clone 55 k‐2 (Dako Corporation, Carpinteria, CA, USA).

Results:  Fascin labeled all sarcomas and all keratinocytic neoplasms except for pagetoid pattern Bowen's disease. The regions of most intense fascin labeling were seen in the basal cells of infiltrative tumor margins. A minority of Merkel cell carcinomas exhibited weak or absent immunoreactivity. All melanocytic nevi except for some junctional nests of dysplastic melanocytic nevi expressed fascin. However, pagetoid cells of melanoma in situ and epithelioid cells of invasive melanoma weakly expressed or did not express fascin, whereas melanoma cells exhibiting spindle cell morphologies labeled intensely with fascin. Lastly, all cells of extramammary Paget's disease and most associated adenocarcinomas cells did not or were faintly labeled by fascin antibodies. Decreased or absent fascin expression was significantly associated with skin cancers with a high risk for metastasis (e.g. melanoma) vs. those with a low risk (e.g. basal cell carcinoma) (24% vs. 100% with > 50% immunoreactivity; p = 0.0001, chi‐squared test).

Conclusion:  Fascin is expressed by skin tumors that locally infiltrate and replace surrounding tissues indicating a role for fascin in cell adhesion, cell motility and invasiveness. No or weak fascin expression is exhibited by cancers with pagetoid intraepidermal spread and by invasive tumors with a high risk of metastasis. Downregulation or loss of fascin's actin‐bundling properties, probably associated with disorganization of cell–cell and cell–matrix contacts, may be a crucial step in the progression from locally invasive to widely disseminating cancers.
Proliferating trichilemmal tumor with a malignant spindle cell component
Authors: Plumb Stephen J. , Stone Mary Seabury
Published: March 2003

Background:  Proliferating trichilemmal tumors (PTTs) are uncommon exuberant growths of cells derived from the external root sheath. They tend to occur in older women, with a predilection for the scalp. Resection is usually curative. Spindle cell components arising within PTTs are exceedingly rare, with only three known cases previously reported. Of these three cases, one patient died from widespread metastasis.

Methods:  Histological and immunohistochemical examinations were performed on a tumor from a 54‐year‐old man which, after exhibiting slow growth for 3 years, increased rapidly in size.

Results: Microscopic examination revealed cystic lobules of squamous cells without a granular cell layer surrounding amorphous eosinophilic debris within the dermis. Also present was a poorly circumscribed focus of spindle cells with hyperchromasia, pleomorphism, giant cells, and abundant mitoses, including abnormal forms. Immunohistochemistry showed the spindle cells to stain positively for vimentin, but negatively for keratin, epithelial membrane antigen and S‐100 antibodies.

Conclusion:  A malignant spindle cell component arising within a PTT is a rare neoplasm which has been associated with death from widespread metastasis.
Intravascular myopericytoma
Authors: McMenamin Máirín E. , Calonje Eduardo
Published: March 2003

Background:  Myopericytoma is a benign tumor composed of cells that show apparent differentiation towards putative perivascular myoid cells called myopericytes. It arises most commonly in the dermis or subcutaneous tissue of the extremities in adults.

Methods:  We describe a myopericytoma that was unusual in its intravascular location.

Results:  A 54‐year‐old man presented with a 10‐year history of a painful slowly growing 1.5‐cm nodule in the subcutaneous tissue of the thigh. Histologic examination of the excised lesion showed that is was entirely contained within the lumen of a vein. It was composed of a proliferation of myoid‐appearing spindle cells, which were arranged in a striking concentric pattern around numerous blood vessels, in a manner that accentuated the vessel walls. This pattern is characteristic of myopericytoma. In some areas, fascicles of spindle cells, embedded in a myxoid stroma, bulged into the lumina of lesional vessels, reminiscent of myofibroma/myofibromatosis. Lesional spindle cells were diffusely positive for smooth muscle actin, focally positive for CD34 and were negative for desmin, cytokeratin, S100 protein, HMB‐45 and CD31.

Conclusion:  This case illustrates that myopericytoma can be entirely intravascular in its location.
An assessment of oral self‐care level among Japanese dental hygiene students and general nursing students using the Hiroshima University – Dental Behavioural Inventory (HU‐DBI): Surveys in 1990/1999
Authors: Kawamura Makoto , Ikeda‐Nakaoka Yumi , Sasahara Hisako
Published: March 2003

Purpose: The purpose of this study was to determine the differences in oral self‐care levels between Japanese dental hygiene students and general nursing students in 1999, and compare them with a similar study in 1990.

Methods: The examination was mainly based upon responses to a questionnaire titled ”Hiroshima University – Dental Behavioural Inventory (HU‐DBI)“. Higher scores of the HU‐DBI indicate better oral health attitudes/behaviour.

Results: The mean HU‐DBI score of the 2nd‐year dental hygiene students was significantly greater than that of the 2nd‐year nursing students (9.56 and 6.65, respectively; p<0.001), and much higher than those of the 1st‐year students at each course (dental hygiene course; 6.30, nursing course; 5.88). Except for the 2nd‐year dental hygiene class, there were no significant differences in the HU‐DBI score between the 1990 and 1999 subgroups of each class. About 1/3 of the 2nd‐year nursing students reported a belief that they may eventually require false teeth, while 6% of the 2nd‐year dental hygiene students held this belief. More than 60% of this study sample stated that they put off going to the dentist until they had toothache. The 2nd‐year dental hygiene students were more likely to have this attitude than their 1990 peers. Flossing was not popular among the nursing students in either 1990 or 1999.

Conclusion: Although the difference in the HU‐DBI score across time was not major, the variation in HU‐DBI and the favourable attitudes/behaviour toward oral health appeared to reflect the differences in schooling between student hygienists and student nurses.
Students’ perceptions of seminar and lecture‐based teaching in restorative dentistry
Authors: Brunton Paul A. , Morrow Leean A. , Hoad‐Reddick Gillian , McCord J. Fraser , Wilson Nairn H. F.
Published: March 2003

In an era of self‐directed learning, it is important to seek the views of dental students regarding their learning experience. Using an anonymous questionnaire, clinical dental students’ perceptions of seminar and lecture‐based teaching in restorative dentistry were sought. 116 of 136 questionnaires circulated were returned for analysis giving a response rate of 85%. Clinical seminars as opposed to lectures were, in the opinion of the students, a more effective way of learning, more relevant to self‐development and more interactive. Seminar‐based learning was considered to be more amenable to self‐direction than formal didactic lectures. It is concluded that the students included in this study were found to prefer seminar‐based learning opportunities as opposed to more traditional styles of learning, specifically, didactic lectures.
Characteristics and study motivation of Danish dental students in a longitudinal perspective
Authors: Vigild Merete , Schwarz Eli
Published: March 2003

This survey encompasses 3 comparable datasets of newly admitted dental students in 1972 (n=236), 1982 (n=197), and 1994 (n=108). The objectives of the survey were to describe selected socio‐demographic characteristics of dental students and to analyze possible changes over time as well as possible changes in the reasons reported by the students for choosing dentistry as a career, their motivations and their expectations concerning the study and the profession of dentistry. The results showed that the ratio of women to men remained unchanged at 6:4 in all 3 cohorts of students and that the students were increasingly recruited from the 2 upper social classes. The motives for choosing dentistry mainly included altruistic motives, the desire for varied work with the opportunity to put theory into practice, economic rewards, and the implicit social status. Compared to the 1972 students, those in 1994 placed greater emphasis on social status as a motive, on the opportunity to work in the biological and scientific field, and on the ready availability of work outside Denmark. The students in all 3 years had strong altruistic motives for choosing dentistry, and it would seem that this stable continuity in the cohort of dental students would ensure the continuous controlled development of dentistry in the new millennium.
Is there a link between writing ability, drawing aptitude and manual skills of dental students?
Authors: Gillet Dominique , Quinton André , Jeannel Alain
Published: March 2003

In France, students have to choose between medical or dental courses, according to their rank, after a competitive examination at the end of their first year of study. Intellectual ability is evaluated, while manual competence is not, and this is a paradox. The purpose of the present study is to investigate whether it is possible to predict the manual aptitude of a dental student through tests that allow the qualities of reflection and organization to be judged. We administered writing tests and drawing tests to 45 students of the Bordeaux dental school to ascertain whether there was a correlation between the competitive examination, the criterion examined (reflection, organization, aesthetics…) and the results of the dental practical assessments during the first year of dental study. The results showed that although manual competence in dental practical work, graphic qualities and writing skills are connected, it is difficult to correlate them directly with competitive examination performance. In view of the number of uncontrolled variables influencing the students' outcome, is it useful to be able to predict who will become a good practitioner? One indication may be found in the moral reasoning of candidates.
Variable responses of waterfowl breeding populations to long‐term removal of introduced American mink
Authors: Nordström Mikael , Högmander Jouko , Nummelin Jukka , Laine Jarmo , Laanetu Nikolaj , Korpimäki Erkki
Published: March 2003

It is suspected that feral American mink, an introduced predator in Europe, have seriously affected local densities of birds breeding in archipelagos and coastal areas. We studied the effects of mink removal on breeding densities of waterfowl in two manipulation and two control areas in the outer archipelago of SW Finland, Baltic Sea. The study was conducted in two phases: during 1992–2001 a total of 98 mink was removed from 60 islands and islets (total area 72 km2) whereas on 37 islands and islets (35 km2) mink was not removed. Additional mink removal and control areas were established during 1998–2001 to replicate the experiment. The breeding densities of the shelduck, tufted duck and the velvet scoter increased as a response to mink removal, while in the control areas their populations remained unchanged. The breeding densities of mallards increased during the first 7 yr of mink removal, but a steep decrease in the last study year resulted in a statistically non‐significant overall increase. The species with low breeding densities (the gadwall, northern shoveler, pintail and the red‐breasted merganser) increased as well. In contrast, the populations of large waterfowl species, the mute swan, greylag goose, common eider and the goosander, did not show obvious increases in breeding densities after mink removal. We conclude that feral mink may locally limit the breeding densities of some smaller waterfowl species and thus reduce the diversity of the waterfowl community in the outer archipelago.
Large‐scale patterns of summer and winter bird distribution in relation to farmland type in England and Wales
Authors: Atkinson Philip W. , Fuller Robert J. , Vickery Juliet A.
Published: March 2003

Over the last 30 yr, the loss of traditional crop rotations and the polarisation of pastoral and arable farming have led to a marked reduction in mixed agriculture in Britain at both the individual farm and the landscape scale. We assess the potential impact of this change on lowland farmland birds by examining the extent to which distributions (as shown by national atlases of summer and winter birds) of different species are associated with arable, pastoral or mixed‐farming landscape types. Relatively few species appeared as either widespread generalists, equally associated across the three broad farmland types, or specialists associated only with one landscape type. Most were associated with two farmland types but distributions showed seasonal differences. During the breeding season there was an approximate ratio of 2:2:1 of species associated with arable, mixed and pastoral landscapes. However, in winter, most species were at highest abundance in mixed farming landscapes. This coincided with a reduction in the number of species associated with pastoral landscapes relative to the breeding season, whereas the number of species associated with arable landscapes remained relatively stable. These patterns are likely to be related to foraging requirements; granivorous birds tended to be associated with arable habitats, which tend to be more seed‐rich, and invertebrate‐feeding species tended to be associated with mixed or pastoral ones, which may be more invertebrate‐rich. The relative importance of mixed landscapes in winter was attributed to seasonal changes in the distribution of some invertebrate feeders, particularly small insectivores (pipits, chats and wagtails), and some of those species considered to be widespread in summer. The results have two important implications for future research. First, most research on farmland birds has, to date, focused on species associated with arable farming during the breeding season. More research is required on species associated with agricultural grasslands, reflecting its importance for farmland birds in Britain, and on the winter ecology of farmland birds in general. These results also emphasise the importance of mixed habitats for farmland birds, particularly in winter, and suggest that further changes in agricultural practices causing reduction in habitat diversity will be detrimental for the farmland bird community. However, widespread benefits may be derived from small scale measures that increase habitat diversity within farmland, for example field margin management options within agri‐environment schemes and support for traditional farming practices in some Environmentally Sensitive Areas.
Incidence of chronic myeloproliferative disorders in the city of Göteborg, Sweden 1983–1992
Authors: Ridell Börje , Carneskog Jan , Wedel Hans , Vilén Lars , Dufva Inge Høgh , Mellqvist Ulf‐Henrik , Brywe Niklas , Wadenvik Hans , Kutti Jack
Published: March 2003

Abstract: An estimation of the incidence of polycythaemia vera (PV), essential thrombocythaemia (ET) and chronic idiopathic myelofibrosis (CIM) in the city of Göteborg, Sweden during the period 1983–1992 was made from a retrospective case analysis of patients registered as chronic myeloproliferative disorders (CMPD) at the Departments of Medicine and the Department of Pathology of the two major hospitals in the city. A total of 125 cases of PV, 56 males and 69 females were identified. The number of cases as well as the age‐specific incidence increased with age. The over all annual gender‐specific incidence was 2.69 cases per 105 male inhabitants and 3.12 cases per 105 female inhabitants. The incidence of PV in relation to the European Standard Population was 2.02 cases per 105 inhabitants and year. There were 72 cases, 20 males and 52 females, with ET. The age‐specific incidence was in all ages higher for females than for males and increased with age. The annual gender‐specific incidence was 0.96 per 105 male inhabitants and 2.35 per 105 female inhabitants. The incidence of ET in relation to the European Standard Population was 1.28 per 105 persons and year. There were 20 cases of CIM, 11 males and 9 females. The annual gender‐specific incidence of CIM was 0.53/105 male inhabitants and 0.41/105 female inhabitants. The incidence of CIM in relation to the European Standard Population was 0.31 per 105 persons and year. Seven persons, 2 males and 5 females, had a CMPD that could not be included in any of the above‐mentioned groups, but were registered as CMPD, unclassified.
Improvement of extrathymic T cell type of large granular lymphocyte (LGL) leukemia by cyclosporin A: the serum level of Fas ligand is a marker of LGL leukemia activity
Authors: Saitoh Takayuki , Karasawa Masamitsu , Sakuraya Masataka , Norio Nakamura , Junko Tohma , Shirakawa Kamon , Matsushima Takafumi , Tsukamoto Norifumi , Tamura Jun'ichi , Naruse Takuji , Murakami Hirokazu
Published: March 2003

Abstract: We report a case of γδ T‐cell‐type large granular lymphocyte (LGL) leukemia (CD3+,CD8+, CD57+,TCR γδ+), which was accompanied by pure red cell aplasia, neutropenia and thrombocytosis. Southern blotting analysis of the T‐cell receptor β gene showed the germline configuration, but clonal TCR J γ rearrangements were identified. These granular lymphocytes demonstrated non‐major histocompatibility complex‐restricted cytotoxicitity. The serum‐soluble FasL (sFasL) concentration of this patient was very high, whereas the serum levels of tumor necrosis factor alpha (TNF‐α), interferon gamma (IFN‐γ), interleukin‐1 beta (IL‐1β), interleukin‐2 (IL‐2) and thrombopoietin were normal. After treatment with cyclosporin A, anemia and thrombocytosis were improved, and LGL and the elevated sFasL concentration decreased. These observations suggested that FasL may have played a role in the establishment of the clinical symptoms of this patient and could be useful as an indicator of disease activity.
Blood haemoglobin declines in the elderly: implications for reference intervals fromage 70 to 88
Authors: Nilsson‐Ehle Herman , Jagenburg Rudolf , Landahl Sten , Svanborg Alvar
Published: March 2003

Abstract: The objective was to determine whether Hb declines in healthy elderly men and women and if this influences health‐related reference intervals. A representative population sample, comprising 30% of all 70‐yr‐old subjects in a Swedish city with 420,000 inhabitants (n=1148, participation rate 85%), was followed at 1–5‐yr intervals for 18 yr within a longitudinal population study. Age‐related changes in Hb were calculated after exclusion of non‐healthy probands and by multivariate analyses in the total study group. Mean Hb declined between age 70 and 88 from 149 to 138 g/L in men (annual decline 0.69 g/L, p=0.000), and from 139 to 135 g/L in women (annual decline 0.06 g/L, n.s.). Healthy men declined from 152 to 141 g/L (annual decline 0.53 g/L, p=0.038), for women from 140 to 138 g/L (annual decline 0.05 g/L, n.s.). Age and body mass index correlated, in multivariate analysis, independently to Hb in both men and women, as did variables indicating a non‐healthy state. Epidemiological decision limits for anaemia declined for men from 128 to 116 g/L, for women from 118 to 114 g/L. Anaemia, thus defined, occurred in 3.2 to 9.7% of the subjects, whereas 28.3% of the 88‐yr‐old men had anaemia according to the WHO definition. In conclusion, there is a significant age‐related decline in Hb from age 70 to 88 among healthy men, and a less pronounced decline among women. This justifies the use of lower epidemiological decision limits for anaemia of about 115 g/L for both men and women from age 80–82.
Effects of sympathetic activation by adrenergic infusions on hemostasis in vivo
Authors: Von Känel Roland , Dimsdale Joel E.
Published: March 2003

Abstract: Overactivity of the sympathetic nervous system (SNS) has been related to increased cardiovascular morbidity. Historical reports suggest hastening of blood coagulation following intravenous administration of epinephrine. Given the important role of the hemostatic system in atherosclerosis and thrombosis, it is surprising that short‐term adrenergic effects on blood coagulation, fibrinolysis and platelet activity have not been scrutinized closely. To elucidate such effects in vivo, this paper reviews human studies in which α‐ and β‐sympathomimetic agents had been infused. The literature suggests a dose‐dependent stimulation of factor VIII clotting activity, von Willebrand factor antigen, tissue‐type plasminogen activator, and platelets within a 15‐ to 40‐min infusion of epinephrine. Precise mechanisms underlying hemostatic changes with sympathetic activation remain to some extent speculative. However, there is evidence from adrenoreceptor blockade studies that coagulation and fibrinolysis molecules are released into circulation by stimulation of vascular endothelial β‐adrenoreceptors (most likely β2‐receptors). Combined α2‐ and β2‐adrenoreceptor‐related mechanism(s) are responsible for platelet activation. Short‐term activation of the SNS effects regular hemostatic activity. While in healthy individuals the hemostatic balance between coagulation and fibrinolysis may be preserved, catecholamine surge may trigger a hypercoagulable state and enhance the odds of overt thrombosis in patients with atherosclerotic disease.
HPA‐1a‐mediated platelet interaction with monocytes in vitro: involvement of Fcγ receptor (FcγR) classes and inhibition by humanised monoclonal anti‐FcγRI H22
Authors: Wiener E. , Mawas F. , Coates P. , Hossain A. K. , Perry M. , Snachall S. , Deb P. , Rodeck C.H. , Keler T.
Published: March 2003

Abstract: To gain insight into mechanisms of platelet destruction and its possible inhibition during fetal/neonatal alloimmune thrombocytopenia (FAIT/NAIT) the binding to monocytes (Mo) of anti‐HPA‐1a‐sensitised platelets, the initial step in IgG‐mediated destruction by effector cells, was evaluated in an in vitro assay. Neonatal Mo were compared with adult Mo as effectors in the assay. Moreover, the potential involvement of Fcγ receptor (FcγR) classes during platelet destruction in the disease was tested by using FcγR class‐specific reagents as inhibitors of the binding reaction. Neonatal Mo were 37% less active than adult Mo in their interaction with anti‐HPA‐1a‐sensitised platelets (p<0.05). The FcγRI‐specific reagents human monomeric IgG and humanised anti‐FcγRI monoclonal H22 caused virtually complete inhibition of platelet binding to Mo. When compared to an intravenous immunoglobulin preparation the inhibitory activity of H22 was 10–100× greater than that of the latter compound. Monoclonal anti‐FcγRII IV.3 and anti‐FcγRIII 3G8 decreased platelet binding by 70% and 64%, respectively, but only the anti‐FcγRII inhibition was statistically significant (p<0.001). Finally, anti‐HPA‐1a‐sensitised platelets bound to 131H‐ but not to 131R‐ FcγRIIa transfected 3T6 mouse fibroblasts (p<0.01), in an anti‐HPA‐1a‐concentration‐dependent manner.

The results suggest that FcγRI and FcγRIIa may be involved in anti‐HPA‐1a‐mediated platelet destruction by mononuclear phagocytes during FAIT/NAIT. Moreover, the much greater potency of monoclonal H22 than of intravenous immunoglobulin as an inhibitor of anti‐HPA‐1a‐mediated Mo‐platelet interaction, might render it superior to the latter agent in the maternal therapy of the disorder.
Low platelet count and elevated serum thrombopoietin after severe trauma
Authors: Hobisch‐Hagen Petra , Jelkmann Wolfgang , Mayr Andreas , Wiedermann Franz , Fries Dietmar , Herold Manfred , Klingler Anton , Schobersberger Wolfgang
Published: March 2003

Abstract: Platelet count is regularly low in patients after multiple trauma, mainly due to blood loss and dilution. Thrombopoietin (TPO) is the main regulator of the circulating platelet mass. Under several clinical conditions an inverse correlation between TPO and the circulating platelet mass was reported. Since platelets bind and internalize TPO, a platelet‐dependent regulation of TPO was suggested. Thus, acute blood loss should be accompanied by elevated TPO. We measured serum TPO, platelets, interleukin‐6 (IL‐6) and vascular endothelial growth factor (VEGF) in 17 multiple traumatized victims. Blood was collected within 12 h after trauma as well as in the morning of days 2, 4, 6 and 9 after admission at the intensive care unit. Platelet count was low at admission and remained low until day 4. Thereafter platelets increased until day 9. TPO nearly doubled within the first 2 d, reaching its maximum on day 6. IL‐6 was initially very high and steadily decreased until day 9. VEGF increased 3‐fold during the 9 d. Statistically significant correlations of TPO were found with platelets and IL‐6, but not with VEGF. In multiple traumatized patients low platelet count is followed by a rapid increase in serum TPO. This fits into the concept of a feedback regulation between circulating TPO and platelet mass.
Stromal cells in lymph nodes attractB‐lymphoma cells via production ofstromal cell‐derived factor‐1
Authors: Arai Junko , Yasukawa Masaki , Yakushijin Yoshihiro , Miyazaki Tatsuhiko , Fujita Shigeru
Published: March 2003

Abstract: Stromal cell‐derived factor‐1 (SDF‐1) is a chemokine produced by bone marrow stromal cells which plays an important role in B‐lymphopoiesis and the homing of hematopoietic stem cells to the bone marrow. In the present study, we investigated the role of SDF‐1 and its receptor, CXCR4, in the chemotactic interaction between non‐Hodgkin B‐lymphoma cells and lymph node stromal cells. SDF‐1 mRNA was abundantly expressed in stromal cells isolated from the lymph nodes of patients with malignant lymphoma. All B‐lymphoma cells freshly isolated from these patients and most laboratory B‐lymphoma cell lines, including follicular, diffuse large, and Burkitt's lymphoma cells, expressed surface CXCR4 and migrated in the presence of recombinant human SDF‐1α. Chemotaxis assays revealed that CXCR4‐positive (but not CXCR4‐negative) B‐lymphoma cells migrated towards lymph node stromal cells, and this migration was almost completely inhibited by the addition of anti‐CXCR4 monoclonal antibody to the lymphoma cells or of anti‐SDF‐1 neutralizing antibody to the culture supernatant of the stromal cells. Down‐regulation of surface CXCR4 was detected in B‐lymphoma cells which migrated towards the stromal cells but not in those which showed no migratory response. In addition, contact between the lymphoma cells and the stromal cells resulted in down‐regulation of surface CXCR4 on the lymphoma cells. These data strongly suggest that SDF‐1/CXCR4 is the main chemokine system involved in the chemotactic interaction between B‐lymphoma cells and lymph node stromal cells.
Pregnancy in essential thrombocythaemia: treatment and outcome of 17 pregnancies
Authors: Bangerter M , Güthner C , Beneke H , Hildebrand A , Grünewald M , Griesshammer M
Published: March 2003

Abstract: Objective: To evaluate treatment and outcome of 17 pregnancies in nine patients with essential thrombocythaemia (ET) seen at our institution from 1988 to 1998. Methods: Treatment and outcome of 17 pregnancies in nine ET patients were retrospectively analyzed. Results: Seventeen pregnancies in nine patients with ET resulted in 11 (65%) live births and ended in six (35%) spontaneous abortions. Abortion could not be predicted from ET‐associated complications before (p=0.23) or during (p=0.39) pregnancy. Maternal complications occured during six pregnancies (35%): Three major bleedings in two patients with an acquired von Willebrand disease and two minor bleedings in patients treated with low‐dose acetylsalicylic acid (ASA) were observed during pregnancy or at term; one patient suffered from transient visual loss while pausing low‐dose ASA. Platelet counts prior to pregnancy were significantly higher as compared to the platelet nadir observed during pregnancy (p=0.0017). Postpartum clinical course was uneventful in all patients. No specific treatment was given during 11 pregnancies. Six women received low‐dose ASA during pregnancy followed by low‐molecular‐weight heparin until the end of the sixth week postpartum in five cases. This treatment was correlated with a favourable outcome (live birth versus abortion) when compared to no treatment (p=0.04). Conclusion: Pregnancy in ET can be complicated by first trimester abortion and/or maternal haemorrhage. Our limited observation suggest a positive impact of low‐dose ASA during pregnancy followed by low‐molecular‐weight heparin postpartum on pregnancy outcome in ET; nevertheless, confirmation by prospective documentation is mandatory.
Hydroxyurea therapy in paraparesisand cauda equina syndrome due to extramedullary haematopoiesis in thalassaemia: improvement of clinicaland haematological parameters
Authors: Cianciulli P. , Caravita di Toritto T. , Sorrentino F. , Sergiacomi L. , Massa A. , Amadori S.
Published: March 2003

Abstract: Patients with β‐globin disorders show amelioration of clinical condition by sustained synthesis of fetal haemoglobin in adult life.

We report data on a patient with β°‐thalassaemia genotype and thalassaemia intermedia clinical phenotype. He received therapy with hydroxyurea (20 mg/kg/d) because of the presence of extramedullary masses causing paraparesis, neurogenic bladder and impotence. During therapy, the patient showed an improved clinical picture and a significant increase in total Hb (from 71.8 to 103.2 g/L) and a γ/α globin synthetic ratio (from 0.39 to 0.68). The myelosuppressive effect of hydroxyurea was revealed by a decrease in CFU‐GEMM, BFU‐E, and CFU‐GM. Therefore hydroxyurea can be effective in the treatment of patients with extramedullary haematopoiesis (EMH) who are not transfusion‐dependent and cannot be treated with radiotherapy.
FAB M4 and high CD14 surface expression is associated with high cellular resistance to Ara‐C and daunorubicin: implications for clinical outcome in acute myeloid leukaemia
Authors: Nørgaard Jan M , Olesen Lene H , Olesen Gitte , Meyer Karin , Kristensen Jørgen S , Bendix Knud , Pedersen Bent , Kjeldsen Eigil , Hokland Peter
Published: March 2003

Abstract: In 145 adult patients diagnosed with non‐M3 acute myeloid leukaemia (AML) the relevance of FAB‐subtype and immunophenotype to in vitro cellular drug resistance towards the anthracyclines aclarubicin (Acla) and daunorubicin (Dau), and the nucleoside analogue cytarabine (Ara‐C), as well as other antileukaemic drugs, was investigated using a 4‐d MTT (3‐[4,5‐dimethylthiazol‐2‐yl]‐2,5‐diphenyl tetrazolium bromide) assay. We demonstrate that high CD14 expression is highly significantly associated with high cellular Ara‐C and Dau resistance in univariate as well as multivariate analyses. FAB subtypes with highest and lowest cellular Ara‐C resistance were M4 and M5, respectively (P < 0.01, one‐way anova), whereas FAB subtypes with highest and lowest cellular Dau resistance were M4 and M1, respectively (P < 0.01, one‐way anova). By contrast, no significant differences in cellular drug resistance towards Acla could be demonstrated among FAB subtypes. Furthermore, in two cohorts of AML patients treated by two different regimens for remission induction over a period of 15 yr (1985–94, n = 159 and 1995–99, n = 76, respectively) we demonstrate in univariate analyses a significance of CD14 expression with respect to clinical outcome. With the exception of significance to probability of obtaining complete remission in the first cohort (P = 0.03, logistic regression), this significance was, however, lost in multivariate analyses. It was demonstrated that FAB‐M4 patients were older than M5 patients and that high CD14 expression was associated with the presence of secondary AML and older age. We conclude that although cases with high blast cell CD14 expression (and FAB‐M4 cases) were more resistant to Ara‐C as well as Dau in vitro, the clinical and biological significance of this may be debatable because of interactions with major prognostic factors in AML.
Frequency and prognostic relevance of cyclin D1 dysregulation in multiple myeloma
Authors: Rasmussen Thomas , Knudsen Lene M. , Johnsen Hans Erik
Published: March 2003

Abstract: Objective: Cyclin D1 dysregulation has been found with varying frequencies in multiple myeloma (MM) and has been suggested to be associated with a poor prognosis. The aim of this study was to investigate the frequency of cyclin D1 dysregulation in patients being treated for MM and to test whether cyclin D1 dysregulation is a prognostic factor for MM patients. Methods: To achieve the above aims we designed a highly sensitive and reproducible real‐time reverse‐transcription polymerase chain reaction (RT‐PCR) assay for quantitation of cyclin D1 mRNA. Using this assay, 110 diagnostic bone marrow (BM) samples from patients with MM were screened for cyclin D1 dysfuntion. Results: The real‐time assay was able to detect the presence of 0.01% cyclin D1 positive cells allowing a safe detection in MM BM samples. In 42% (46/110) of MM BM samples a ≥ 3‐fold increase in cyclin D1 mRNA was observed compared to the cyclin D1 level in normal BM. In the remaining group of MM patients the cyclin D1 mRNA levels were comparable to normal donors. Follow‐up of 76 MM patients showed no significant (P = 0.35) difference in survival between cyclin D1 positive and negative MM patients. In addition, cyclin D1 dysregulation did not correlate with known prognostic factors. Conclusion: The developed real‐time RT‐PCR assay for detection of cyclin D1 mRNA levels offers a fast and safe screening for cyclin D1 dysfunction. When a large cohort of MM patients was screened, the cyclin D1 gene was found to be frequently dysregulated, but there was no significant correlation to survival or known prognostic parameters.