bluuebunny/crossref_metadata_2025 huggingface dataset:
Monophasic sarcomatoid carcinoma of the scalp: a case mimicking inflammatory myofibroblastic tumor and a review of cutaneous spindle cell tumors with myofibroblastic differentiation
Authors: Winfield Harry L. , Rosenberg Arlene S. , Antonescu Cristina R. , Weil Michael , Wang Alun R.
Published: December 2004

Background:  The evaluation of malignant cutaneous spindle cell tumors is challenged by a diagnostic differential that comprises neoplasms of diverse histogenesis, and a broad immunohistochemical panel may confound the diagnosis when the results suggest multiple lines of differentiation, such as with a combined myofibroblastic and epithelial phenotype.

Methods:  We report the case of a solitary scalp nodule that quickly became locally metastatic. A comprehensive panel of immunohistochemistry markers and electron microscopy was evaluated to determine the differentiation of the spindle cells.

Results:  The tumor, consisting of wavy and slender spindle cells with predominantly bland nuclei, showed immunoreactivity to vimentin, smooth muscle actin, and muscle‐specific actin. AE1/AE3, CK5/6, and MNF‐116 antibodies were weakly positive in rare cells. However, 34βE12 showed diffuse positivity in the spindle cell population, thus supporting the diagnosis of a sarcomatoid carcinoma with myofibroblastic differentiation.

Conclusions:  The use of 34βE12 is essential for the evaluation of myofibroblastic spindle cell tumors with rare cytokeratin reactivity. However, even with immunohistochemical and electron microscopic studies, the diagnosis of spindle cell tumors can be confounded by the multiplicity of nosologic equivalents, such as carcinosarcoma, spindle cell carcinoma, and metaplastic carcinoma. The nomenclature of these spindle cell tumors is discussed.
Cellular angiofibroma of the vulva: a clinicopathological study of two cases with documentation of some unusual features and review of the literature
Authors: Dargent Jean‐Louis , De Saint Aubain Nicolas , Galdón María Gómez , Valaeys Véronique , Cornut Patricia , Noël Jean‐Christophe
Published: December 2004

Background:  Cellular angiofibroma (CA) of the vulva is a recently described condition, whose clinical and pathological features are poorly known.

Methods:  We have encountered two cases of this very unusual tumor. Their clinical and pathological features were analyzed and compared to those reported in the literature.

Results:  Both patients were middle‐aged women. In each case, the lesion had the clinical appearance of a vulvar cyst, located in the lateral aspect of the clitoris and the right labium majus, respectively. Microscopically, the lesions were well circumscribed but not truly encapsulated. Both were composed of small spindle cells arranged in short fascicles and mixed up with relatively abundant small‐ or medium‐sized rounded vessels. While mitotic activity was perceptible in both cases, no cellular atypia could be demonstrated. A striking feature seen in one case was the presence of pseudoangiomatous changes in the stroma, similar to those occasionally found in spindle cell lipoma. Phenotypically, the tumor cells consistently expressed vimentin, CD99, and both estrogen and progesterone receptors. A discrete CD34 or smooth muscle actin immunoreactivity was also found in one case. No expression of S‐100 protein, Bcl‐2 protein, CD117 (c‐kit gene product), epithelial membrane antigen, desmin, or h‐caldesmon could be demonstrated.

Conclusion:  This study further illustrates that CA of the vulva has distinct clinical and pathologic features that set it apart from the other soft tissue conditions involving this area. However, like many soft tissue neoplasms, this tumor also exhibits some variation in its histological or immunohistochemical features.
Socio‐economic and schooling status of dental undergraduates from six French universities
Authors: Hennequin M. , Tubert S. , Devillers A. , Müller M. , Michaïlesco P. , Peli J. F. , Pouëzat J.
Published: December 2004

Objectives: The aim of this study was to evaluate the socio‐economic status of French undergraduate dental students.

Methods: A 46‐item questionnaire was completed by the dental students of six universities between 1992 and 1995. Subjects related to family background, housing, schooling, income, expenditure and participation in student life were investigated.

Results: A total of 1192 out of 1207 questionnaires were returned. Both genders had equal access to dental training. The average overall cost of the four last years of the dental course was 30,302 French francs and varied greatly between faculties, as did the number of hours spent at the faculty for lectures, tutorials and practicals, and clinical work. Overall, the majority of students came from a well off social background, and had a relatively high quality of life while a small minority received no support from their families. Thirty‐four per cent of students had never worked. One third of students smoked and one third regularly consumed medication of some sort. A third did not participate in any sport. Only 25% students bought dental text books and 42% of the students reported using the library regularly.

Conclusions: This study offers an accurate description of the socio‐economic status of French dental students that could be used as a reference for comparable studies in other European countries.
Large‐scale effect of climate change on breeding parameters of pied flycatchers in Western Europe
Authors: Sanz Juan José
Published: December 2004

Variations in laying date and clutch size of pied flycatchers Ficedula hypoleuca across populations throughout western Europe are examined in relation to climatic fluctuations, measured by the winter North Atlantic Oscillation (NAO) index. Across breeding sites, the winter‐NAO index affected laying date such that females lay earlier after warmer and moister winters (positive values of winter NAO‐index). Female pied flycatchers breed progressively earlier because presumably the whole breeding season is being shifted, as a direct result of the positive values of winter NAO‐index. Moreover, clutch size of pied flycatchers across populations was negatively related to winter NAO‐index during the last 50 yr. These analyses controlled for potentially confounding variables such as latitude, longitude, elevation and habitat of each study site. The present study conclude that pied flycatchers across western Europe are breeding earlier and laying smaller clutch sizes and that the most likely cause is a long‐term increase in spring temperature. On the other hand, this study shows that climate change may not act uniformly between breeding populations in Western Europe. From those results, this study concludes that northern pied flycatcher populations are more sensitive to climate change than southern populations breeding in montane habitats.
Effect of forest fragmentation on dung beetle communities and functional consequences for plant regeneration
Authors: Andresen Ellen
Published: December 2004

I compared dung beetle communities and assessed some of their functional effects (dung removal, seed burial, seedling establishment) in continuous forest with those in 1‐ha and 10‐ha forest fragments in Central Amazonia. I followed the fate of seeds until seedling establishment for three native tree species, using clean seeds and seeds surrounded by dung. The 1‐ha fragments had half the number of dung beetle species captured in continuous forest and in 10‐ha fragments. The continuous forest sites and the 1‐ha fragments had similar number of individuals, but in the 10‐ha fragments dung beetles were twice as abundant. Mean beetle size increased with increasing forest area. Dung removal and seed burial rates were higher in continuous forest than in forest fragments. Seed predation rates were higher in the forest fragments. In all sites, the proportion of seedlings established from seeds surrounded by dung vs clean seeds was the same, and it was the same in continuous forest vs fragments. When comparing seeds that remained on the forest floor with seeds buried by dung beetles, a higher percentage of seedlings established from the latter. Conservation programs that aim to maintain the regeneration ability of forest fragments must incorporate all the important components involved in seedling establishment; in Central Amazonia these include dung beetles as secondary dispersers. It is important that studies start measuring directly not only the first‐order effects of forest fragmentation on species, but also the higher‐order functional effects.
Foraging behaviour and diet of an ectothermic herbivore: Testudo horsfieldi
Authors: Lagarde Frédéric , Bonnet Xavier , Corbin Johanna , Henen Brian , Nagy Ken , Mardonov Baktjior , Naulleau Guy
Published: December 2004

Herbivorous vertebrates of arid regions are frequently faced with inadequate food quality, quantity or both. The time and energy devoted to foraging is vital to balancing their energy budgets. For desert ectotherms, a low metabolism should be advantageous, reducing their total energy requirement, but extreme ambient temperatures can strongly constrain these animals’ activity periods. We provide the first data on the activity budgets, foraging behaviour and diet of a highly abundant, desert‐dwelling, herbivorous ectotherm, the steppe tortoise Testudo horsfieldi. Extreme climatic conditions of Central Asia limit steppe tortoise's activity to only three months per year. They remain inactive most of their “active season” (90%), and spend very little time foraging (<15 min per day). This suggests that steppe tortoises can satisfy their energy requirements with modest feeding efforts. Interestingly, steppe tortoises avoid feeding on grass species and feed mostly on plant species that are usually highly toxic to mammals. This result suggests that steppe tortoises and ungulates do not compete for food.
Dispersal characteristics of three odonate species in a patchy habitat
Authors: Angelibert S. , Giani N.
Published: December 2004

Dispersal has a potentially profound effect on the dynamics of populations especially when a population occupies a patchy habitat. Ponds surrounded by terrestrial landscape are an example of patchy distribution of physical conditions and constitute “islands” for odonates. Few studies have focussed on dispersal in odonates. We have used the direct method of dispersal observing (capture‐mark‐recapture technique) in order to estimate the degree of linkage in three patchy populations of odonate localised on three ponds. We also examined the differences in dispersal ability within and among three species (Coenagrion puella, Coenagrion scitulum and Libellula depressa). The ponds were situated in southwest France on a limestone plateau. In this arid area, these ponds constitute the only surface water available and are relatively sparsely distributed. The size of the ponds ranged from 48 to 79 m2 and they were 200 and 775 m apart. We demonstrated that three factors influence the dispersal ability of these odonates. The first is represented by the abiotic factors and especially weather conditions. This determines the number of days that dispersal is possible. The second is interspecific differences. We showed that sensitivity to weather conditions, species size and species behaviour influence dispersal ability. The third factor is the intraspecific characteristics. We demonstrated that there are differences in dispersal ability according to sex and age. To conclude, we discuss the importance of pond management to maintain the existing odonate populations and to facilitate introduction of new populations in this region where little exchange occurs between ponds.
Life history, diversity and distribution: a study of Japanese pteridophytes
Authors: Guo Qinfeng , Kato Masahiro , Ricklefs Robert E.
Published: December 2004

Many studies address the relationships between diversity or distribution and attributes of the physical environment. However, how these relationships are connected to variation in life history is poorly understood. This is particularly true in the case of pteridophytes. Japanese ferns and their allies comprise one of the best‐known pteridophyte floras in the world. We analyzed ca 600 species of Japanese pteridophytes for which there is detailed information on distribution, reproduction, and chromosome number. Species richness was greatest in groups with a single reproductive mode (sexual, followed by apogamous), but distribution was greatest in species groups with multiple reproductive modes: sexual plus either sterile (irregular in meiosis) or apogamous. Geographical ranges varied greatly among species with small chromosome numbers but were uniformly small among species having high chromosome numbers. Seasonally green (mostly summer green) species had significantly larger distribution ranges than evergreen species. Endemic species had higher proportions of apogamy and sterility than non‐endemic species. Seasonally green species had significantly larger distributional ranges, and a smaller proportion of species with apogamous reproduction, than evergreen species. There was no clear relationship between distribution and spore size, either among endemic species, non‐endemic species, or all species combined. There was no relationship between spore size and chromosome number when all species were combined. However, positive relationships were detected within three of the nine largest genera, suggesting potential phylogenetic effects. We concluded that habitat availability, rather than dispersability, may be the limiting factor for the distribution of pteridophytes in Japan.
Impact of the factor II: G20210A variant on the risk of venous thromboembolism in relatives from families with the factor V: R506Q mutation
Authors: Rintelen C. , Pabinger I. , Bettelheim P. , Lechner K. , Kyrle P. A. , Knöbl P. , Schneider B. , Mannhalter C.
Published: December 2004

Abstract: Objectives: Factor V: R506Q mutation and the prothrombin G20210A variant (factor II: G20210A variant) are associated with an increased risk of venous thromboembolism (VTE). In cohorts of unrelated patients a cosegregation of both mutations has been shown to be associated with an increased risk of developing VTE. The aim of this study was to investigate the impact of the coinheritance of both mutations on the risk of VTE in relatives of symptomatic carriers of the factor V: R506Q mutation and the factor II: G20210A variant. Patients and methods: Four families with 48 family members were investigated for the presence of the factor V: R506Q mutation and the factor II: G20210A mutation, and their clinical history was evaluated. Results: VTE was more frequent in family members with a combined defect (3/10; 30%) compared to those with a single mutation (1/16; 6%) or without a defect (1/12; 8%). The probability for VTE for 40‐yr‐old individuals with both mutations, a single mutation and no mutation was 56%, 12% and 20%, respectively. Conclusions: These data suggest that the G to A transition at position 20210 of the prothrombin gene leads to an increase in the risk of VTE in carriers of the factor V: R506Q mutation. The determination of the factor II: G20210A variant in index patients carrying a factor V: R506Q mutation and, if present, in family members may help to identify individuals who are at high risk for VTE.
Hairy cell leukemia in first cousins and review of the literature
Authors: Colovic Milica D. , Jankovic Gradimir M. , Wiernik Peter H.
Published: December 2004

Abstract: Familial hairy cell leukemia (HCL) occurs rarely. So far, 26 familial instances of HCL (in 12 families) have been reported in the literature. The consistent human leukocyte antigen (HLA) linkage could not be established in most cases of familial HCL. History of exposure to organic chemicals or employment in woodworking or farming was noted in only two out of 11 affected families. We present two familial cases of HCL as well as a thorough literature review. An influence of HLA or farming themselves on a predisposition to HCL remains unproven but does not rule out an HLA‐linked and as yet unidentified gene responsible for increased disease susceptibility. HCL in families is unlikely to be due to random patterning, but there are insufficient data so far to decisively incriminate either HLA‐related or environmental causative factors.
Squamous cutaneous epithelial cell carcinoma in two CML patients with progressive disease under imatinib treatment
Authors: Baskaynak Gökben , Kreuzer Karl‐Anton , Schwarz Michaela , Zuber Johannes , Audring Heike , Riess Hanno , Dörken Bernd , Le Coutre Philipp
Published: December 2004

Abstract. Imatinib (glivec®, formerly known as STI571) effectively blocks the ATP‐binding site of the bcr/abl fusion protein thereby inactivating selectively the tyrosine kinase activity of bcr/abl. Therefore, it is a promising drug in Philadelphia chromosome positive chronic myeloid leukemia showing high hematologic and cytogenetic response rates combined with a mild toxicity profile. Here we report two cases of squamous cell carcinoma of the skin, which appeared in the photoexposed areas in two elderly patients treated for advanced chronic myeloid leukemia with imatinib. The role of chemotherapy, chronic sun exposure and of possible additional risk factors such as human papillomavirus infection is discussed.
Signet ring‐like light chain myeloma with systemic spread
Authors: Haidar Joud H. , Bazarbachi Ali , Nasr Michel R. , El‐Sabban Marwan E. , Daher Rose
Published: December 2004

Abstract: The morphological presentation of malignant plasma cells in multiple myeloma (MM) varies from mature to anaplastic plasma cells with only one reported case of signet ring variant. We describe here another case of signet ring‐like lambda light chain MM associated with extra‐skeletal spread to lymph nodes, spleen and liver. The clinical and pathological presentations were atypical with no evidence of bone‐lytic lesions or monoclonal component on protein electrophoresis, leading to a delay of several years in the diagnosis. Recognition of this morphological entity of MM may help in an early diagnosis of this rare variant.
Complex interaction of Hb Hekinan [α27(B8) Glu–Asp] and Hb E [β26(B8) Glu–Lys] with a deletional α‐thalassemia 1 in a Thai family
Authors: Fucharoen Supan , Changtrakun Yossombat , Ratanasiri Thawalwong , Fucharoen Goonnapa , Sanchaisuriya Kanokwan
Published: December 2004

Abstract: Hemoglobin (Hb) Hekinan (α27; Glu–Asp) is a rare α‐chain variant found mainly in Japanese and Chinese whereas Hb E (β26; Glu–Lys) is common among Southeast Asians. We report a hitherto undescribed condition in which these two variants co‐segregate. The proband was a 25‐yr‐old Thai woman who was encountered with the presence of mild hypochromic microcytosis with Hb 8.2 g/dL, hematocrit (Hct) 26.0%, Mean Corpuscular Value (MCV) 68.6 fL, Mean Corpuscular Hemoglobin (MCH) 21.6 pg and Mean Corpuscular Hemoglobin Concentration (MCHC) 31.5 g/dL. Although Hb electrophoresis at alkaline pH did not show any abnormal band except Hb E in addition to Hb A, high performance liquid chromatography analysis revealed abnormal peaks at the Hb A and Hb E positions. DNA analysis of the proband revealed a GAG–GAT mutation at codon 27 of the minor α1‐globin gene for Hb Hekinan in trans to the South‐east Asian (SEA) deletional α‐thalassemia 1 determinant and a GAG–AAG mutation at codon 26 of the β‐globin gene for Hb E. She was therefore a triple heterozygote for these three anomalies. Family study identified that her mother was a double heterozygote for Hb Hekinan and Hb E without α‐thalassemia whereas her father was a classical Hb H disease patient. The genotype–phenotype relationship observed in this Thai family with complex hemoglobinopathies is presented and a simple DNA assay based on the polymerase chain reaction methodology for rapid diagnosis of Hb Hekinan is described.
A perspective on the measurement of ADAMTS13 in thrombotic thrombocytopaenic purpura
Authors: Pimanda John E. , Chesterman Colin N. , Hogg Philip J.
Published: December 2004

Abstract: The recent discovery of the von Willebrand Factor (vWF) cleaving protease (ADAMTS13) and the association of its deficiency with thrombotic thrombocytopaenic purpura (TTP) has generated both enormous interest and considerable confusion. Ultra large von Willebrand Factor (UL vWF) multimers are present in the plasmas of patients with chronic relapsing TTP in remission but disappear during an attack. This observation led to the recognition that UL vWF multimers precipitate the thrombotic occlusion of arterioles, a feature that characterizes TTP. Multiple mutations in ADAMTS13 are associated with congenital TTP and neutralizing autoantibodies have been demonstrated in the acquired TTP syndrome. Although a number of functional assays for this enzyme have been described, the more rigorously evaluated assays are difficult to perform outside a research laboratory. There is also an enduring uncertainty about the specificity of ADAMTS13 deficiency for the diagnosis of acquired TTP and a perception that the result does not alter patient management. The cloning of the ADAMTS13 gene has also raised the prospect of recombinant enzyme therapy for the treatment of TTP, and this has heightened the need for a simple assay. In this review, we evaluate the value of measuring this enzyme in the management of TTP.
Uneventful outcome of unrelated hematopoietic stem cell transplantation in a patient with leukemic transformation of Kostmann syndrome and long‐lasting invasive pulmonary mycosis
Authors: Dallorso Sandro , Manzitti Carla , Dodero Paolo , Faraci Maura , Rosanda Cristina , Castagnola Elio
Published: December 2004

Abstract: Kostmann syndrome (KS) is an inherited hematological disorder characterized by an absolute neutrophil count (ANC) <0.2 × 109/L and life‐threatening bacterial infections. Granulocyte‐colony stimulating factor (G‐CSF) makes it possible to reach an ANC of 1.0 × 109/L and consequently to reduce significantly the occurrence of severe infections. Absence of response to G‐CSF, G‐CSF receptor mutation, and leukemic transformation are absolute indications to perform hematopoietic stem cell transplantation (HSCT). Pulmonary mycosis does not represent an absolute contraindication to bone marrow transplantation (BMT), although a relapse rate of 30–50% has been reported, despite adequate medical and surgical treatment. Mycotic pneumonia recurrence shows a mortality rate above 80%, especially in the presence of persisting immunosuppression. We report on a KS patient with long‐lasting fungal pneumonia who developed myelodysplasia and subsequent acute myeliod leukemia (AML) conversion resistant to antiblastic therapy. Despite surgical excision and secondary prophylaxis, recurrence of the pulmonary lesion occurred prior to the unrelated HSCT. In spite of these poor prognostic characteristics, outcome was uneventful and the patient is alive and well in continuous complete remission with no signs of fungal infection.
New approaches in the immunotherapy of haematological malignancies
Authors: Costello Régis T. , Rey J. , Fauriat C. , Gastaut J.‐A. , Olive D.
Published: December 2004

Advances in the management of haematological malignancies have allowed to obtain improved remission rates. Nonetheless, relapses impair these results and justify the search for novel therapeutic strategies. Clinical data demonstrate that the immune system plays an important role in the control of haematological malignancies. An increased frequency of haematological malignancies is observed in immunodeficiency states. Reversal of the immunosuppression is sometimes sufficient to induce tumour regression (withdrawal of cyclosporine in post‐transplant lymphoproliferations, highly active anti‐retroviral treatment in human immunodeficiency virus related Kaposi's disease). Another line of evidence for the involvement of the immune system in the anti‐tumour response comes from the observation of spontaneous anti‐tumour responses that parallel the occurrence of paraneoplastic immune‐mediated syndromes. Finally, the efficiency of allogeneic transplantation in the haematological field has been clearly demonstrated to depend on the immune‐mediated graft vs. leukaemia effect. Nonetheless, tumours develop in immune competent patients because of various tumour escape mechanisms, such as loss of human leucocyte antigen class I antigens, absence of target recognition by deficient adhesion/co‐stimulatory molecule expression, tumour cell counterattack against immune effectors, direct (contact‐dependent) or indirect (cytokine‐mediated) impairment of T‐lymphocyte activation. Novel immunotherapy approaches are now orientated in a convergent direction, i.e. the reversal of immune escape mechanisms either via the correction of deficient phases of the immune response or by the amplification of physiological mechanisms.
Effect of catalase supplementation in storage media for avulsed teeth
Authors: Buttke Thomas M. , Trope Martin
Published: December 2004

Abstract  – The type of liquid medium used to store avulsed teeth prior to replantation has been shown to affect the long‐term prognosis. One possibility is that some storage media contain hydrogen peroxide (H2O2) that may be toxic to periodontal ligament cells. Therefore, the aim of this study was to determine if the addition of catalase to storage media improved the prognosis of replanted dog teeth. Forty‐eight mongrel premolar roots were endodontically treated, extracted, randomly divided and placed into one of four storage media: Hank's balanced salt solution (HBSS), containing no antioxidant); Viaspan, containing the antioxidant, glutathione, or the same two media supplemented with catalase(100 U ml−1) for 1, 5, or 26 h prior to replantation. After 2 months, the dogs were euthanized and the roots histologically examined to evaluate the attachment tissues. Regardless of the storage medium used, overall healing was excellent and only 4% of the roots displayed inflammatory or replacement resorption. When roots from the different storage media were compared, those stored in HBSS were found to display the highest incidence of surface resorption (55.7%). Supplementation of HBSS with catalase resulted in a lower level of surface resorption (48.6%) that was statistically significant (P < 0.05). Roots stored in Viaspan – or + catalase displayed even lower levels of surface resorption (41.3 and 38.2%, respectively). The improvement observed with catalase‐supplemented HBSS was confined to the 45‐min incubation period; only Viaspan – or + catalase reduced surface resorption at the 5‐ and 26‐h incubations. Collectively, these data demonstrate that roots stored in media containing antioxidant activity undergo less surface resorption. These results suggest that low levels of H2O2 in storage media for avulsed teeth may adversely affect periodontal ligament cells.
Cytokeratin 7 and 20 expression in epithelioid sarcoma
Authors: Humble Scott D. , Prieto Victor G. , Horenstein Marcelo G.
Published: December 2004

Background:  Epithelioid sarcoma (ES) is a rare malignant soft tissue tumor of uncertain histogenesis that arises predominantly in the extremities of young adults. Immunohistochemically, the neoplastic cells are typically positive for vimentin, low molecular weight cytokeratin (CAM5.2) and epithelial membrane antigen (EMA).

Method:  We examined eight cases of ES from seven different patients. All cases were studied with immunohistochemistry for EMA, CAM5.2 (keratin 8 and 18), 34BE12 (keratins 1, 5, 10 and 14/15), cytokeratins 7 and 20 (CK7, CK20), and CD34.

Results:  The average patient age was 53 (range 43–76) and the male:female ratio was 5:2. The location was the upper extremity in five tumors, the lower extremity, the perineum, and the paraspinal soft tissue in one tumor each. All cases contained predominantly epithelioid cells, but spindle cells were also present in three cases. All cases contained areas of geographic necrosis. CAM5.2 was strongly positive in seven tumors and focally positive in one (8/8). EMA was diffusely positive in two cases and focally positive in five cases (7/8). CD34 was diffusely positive in 3/8 cases. 34BE12 was diffusely positive in one case and focally positive in two others (3/8). CK7 was diffusely positive in one case and focally positive in another (2/8). CK20 was negative in all cases (0/8). All cases tested were positive for vimentin (6/6), 2 cases were focally positive for HHF35 (2/5), and all cases tested were negative for S‐100 protein (0/7).

Conclusions:  In addition to the known immunoreactivity for CAM5.2 and EMA, there is positivity for CK7 and 34BE12 in a small proportion of cases. None of the cases expressed CK20. This immunophenotypic profile suggests that ES is more similar to carcinoma and synovial sarcoma than to other soft tissue tumors, and may be of diagnostic utility.
Erythropoietin has an anti‐myeloma effect – a hypothesis based on a clinical observation supported by animal studies
Authors: Mittelman Moshe , Zeidman Aliza , Kanter Pazit , Katz Odelia , Oster Howard , Rund Debbora , Neumann Drorit
Published: December 2004

Recombinant human erythropoietin (rHuEpo) was introduced into clinical practice more than a decade ago, and has been found to be effective in the treatment of several types of anemia, including anemia of end‐stage renal failure and cancer‐related anemia. No study has suggested that Epo might have an effect on the biology of the disease, nor any survival advantage to cancer patients treated with Epo for anemia has been reported. Here we report six patients with advanced multiple myeloma (MM) with very poor prognostic features, whose expected survival was <6 months. All six patients were treated with rHuEpo for their anemia, either without any chemotherapy or very mild chemotherapy for a short time. Yet, surprisingly they lived for 45–133 months totally from MM diagnosis and 38–94 months with rHuEpo (with a good quality of life). In fact, one patient, is still alive and well, more than 8 yr after chemotherapy was discontinued because of a resistant aggressive disease. The course in these six MM patients led us to hypothesize that Epo might have an antineoplastic or antimyeloma effect. We proceeded and tested that hypothesis in mouse models of myeloma (Mittelman M et al., Proc Natl Acad Sci USA 98:5181,2001). In these models we confirmed that rHuEpo induced tumor regression in about 50% of the BALB/c mice inoculated with MOPC‐315 myeloma cells. We then presented evidence that the mechanism is a new immune‐mediated phenomenon, via activation of CD8+ T cells. Furthermore, evidence from the literature supports the antineoplastic effect of Epo. Epo might be used as an adjunct immune treatment in various malignant diseases, in addition to the current regimens and chemotherapeutic protocols. Fututre trials should determine the role of Epo in myeloma and cancer treatment, besides clarifying concerns about the presence of Epo receptors on some tumor cells.
Ethical problems in cytology
Authors: Znidarčić Ž.
Published: December 2004

Great advances in medical science have raised a number of ethical issues, many of which affect cytopathology. Some of the main issues addressed in this paper relate to the organization of a cytology laboratory: internal and external quality control, adequate staffing levels and staff education, cytopathology reporting format and contents, confidentiality issues, relationship with the clinicians and involvement of cytopathologists in clinical management teams.

Quality control has to be provided within cytology departments but external quality assurance is also essential, with national monitoring.

New technologies should be used according to the best scientific methods, following cytological analysis.

Scientific work in cytology has to respect the general principles of scientific ethics. The patient's interest has to be the main reason for such work.
Role of fine needle aspiration cytology in the diagnosis of soft tissue tumours and tumour‐like lesions
Authors: Dey P. , Mallik M. K. , Gupta S. K. , Vasishta R. K.
Published: December 2004

In this study, we evaluated the usefulness of fine needle aspiration cytology (FNAC) in the diagnosis of soft tissue tumours. We have also assessed the various pitfalls of FNAC of soft tissue tumours. This was a retrospective study and here we analysed only 82 histopathology proven cases of FNAC of soft tissue tumours diagnosed in a five and half year period. On histopathological examination, 55 of these cases were malignant and 27 were benign. There was a total of 15 recurrences and histopathology was available prior to FNAC in only eight of these cases. Therefore, excluding these eight cases, malignant tumours were primarily diagnosed by FNAC in 47 cases. The sensitivity, specificity and positive predictive value of FNAC in diagnosis of soft tissue tumours were 91.5%, 92.5% and 95.5%, respectively. Only 22 of 47 cases (46.8%) were correctly categorized. There were two false‐positive and four false‐negative cases. One case each of fibromatosis and schwannoma were reported as sarcoma. False‐negative cases were fibrosarcoma (1), malignant nerve sheath tumour (2) and haemangiopericytoma (1). FNAC was very useful in distinguishing benign from malignant soft tissue tumours. However, it was not so effective in exact categorization of tumours.
Induction of apoptosis by hinokitiol, a potent iron chelator, in teratocarcinoma F9 cells is mediated through the activation of caspase‐3
Authors: Ido Y. , Muto N. , Inada A. , Kohroki J. , Mano M. , Odani T. , Itoh N. , Yamamoto K. , Tanaka K.
Published: December 2004

Abstract. Hinokitiol, a potent iron chelator, has been reported to induce differentiation in teratocarcinoma F9 cells with a reduction of viable cells. In this study, we examined the steps leading to eventual cell death by hinokitiol during differentiation. Hinokitiol induced DNA fragmentation of F9 cells in a concentration‐and time‐dependent manner. This effect was also observed in a cell‐free system using the nuclei from intact cells and the cytosols from hinokitiol‐treated cells. In contrast, hinokitiol methyl ether and hinokitiol‐‐Fe (III) complex, which are deficient in iron‐chelating activity, showed no DNA fragmentation activity in both cell culture and cell‐free systems. These results suggest that iron deprivation by hinokitiol may be involved in the induction of apoptosis of F9 cells. Caspase‐3, one of the key enzymes in the apoptotic cascade, was specifically activated by hinokitiol treatment, but not by the other two derivatives. In addition, its specific inhibitor, benzyloxycarbonyl‐Val‐Ala‐Asp‐fluoromethyl ketone, strongly blocked hinokitiol‐induced DNA fragmentation. These results indicate that iron deprivation by hinokitiol can induce apoptosis of F9 cells through the activation of caspase‐3.
Gompertzian growth pattern correlated with phenotypic organization of colon carcinoma, malignant glioma and non‐small cell lung carcinoma cell lines
Authors: Castro M. A. A. , Klamt F. , Grieneisen V. A. , Grivicich I. , Moreira J. C. F.
Published: December 2004

Abstract. In the current study we present a Gompertzian model for cell growth as a function of cell phenotype using six human tumour cell lines (A‐549, NCI‐H596, NCI‐H520, HT‐29, SW‐620 and U‐251). Monolayer cells in exponential growth at various densities were quantified over a week by sulforhodamine B staining assay to produce cell‐growth curves. A Gompertz equation was fitted to experimental data to obtain, for each cell line, three empirical growth parameters (initial cell density, cell‐growth rate and carrying capacity – the maximal cell density). A cell‐shape parameter named deformation coefficient D (a morphological relationship among spreading and confluent cells) was established and compared by regression analysis with the relative growth rate parameter K described by the Gompertz equation. We have found that coefficient D is directly proportional to the growth parameter K. The fit curve significantly matches the empirical data (P < 0.05), with a correlation coefficient of 0.9152. Therefore, a transformed Gompertzian growth function was obtained accordingly to D. The degree of correlation between the Gompertzian growth parameter and the coefficient D allows a new interpretation of the growth parameter K on the basis of morphological measurements of a set of tumour cell types, supporting the idea that cell‐growth kinetics can be modulated by phenotypic organization of attached cells.
Outcome of three consecutive inadequate cervical smears
Authors: Butts S. L. , Wilson E. , Newman J.
Published: December 2004

A retrospective audit of women with three consecutive inadequate cervical smears during 1998–99 was conducted at Birmingham Heartlands Hospital. The commonest reasons were obscured by polymorphs (34.5%) and sparse cellularity (28.9%). Seventy‐three per cent (73%) were followed up at colposcopy and 22.1% had histological assessment; 15.9% of women had an abnormality detected, 10.6% with abnormal histology and 5.3% with a cytological abnormality only. Cytological abnormalities were seen in 11.1% of the screening population. This study did not identify a cytological criterion to differentiate those that would or would not have an abnormality on follow‐up. It is suggested that all women with three consecutive inadequate smears should have adequate follow‐up, although this may place increased demands on colposcopy services.
Effect of circulation and discussion of cervical smears on agreement between laboratories
Authors: Ronco G. , Montanari G. , Confortini M. , Parisio F. , Berardengo E. , Delpiano A. M. , Arnaud S. , Campione D. , Baldini D. , Poll P. , Lynge E. , Mancini E. , Segnan N.
Published: December 2004

The study objective was assessing whether circulation of smears and discussion of those with differing interpretation can increase reproducibility between laboratories. The study included: the blind interpretation of a first set of 194 smears among seven laboratories, the discussion of smears with discrepant diagnoses during the previous phase and the blind interpretation of a second set of smears of same size and characteristics. After discussions, the overall weighted kappa increased in five laboratories (substantially in three : +50%, +27% and +20%). However, no change was observed in one laboratory and a slight decrease (−4%) in another. The latter interpreted the second set of smears at a longer time interval from discussions. Agreement improved for all diagnostic classes except low grade intraepithelial neoplasia (LSIL). Overall, the intervention increased diagnostic agreement, but its effect varied with laboratory and by diagnostic class and could be transient. Continued programmes of smear exchange and discussion appear to be advisable.
Stereotactic biopsy and cytological diagnosis of solid and cystic intracranial lesions
Authors: Collaço L. M. , Tani E. , Lindblom I. , Skoog L.
Published: December 2004

Cytological smears from 115 consecutive cases of stereotactic biopsies of intracranial lesions were reviewed. Ninety‐five lesions were solid and 20 cystic. Material from 90 solid and 13 cystic lesions was sent both for cytological and histological examination. In 66 of the solid lesions, the cytological diagnosis was confirmed by histology (five were benign lesions and 61 malignant tumours: 56 primary brain tumours, three metastases and two lymphomas). In 24 cases with discrepant cytology and histology, the histology was inconclusive or insufficient in 14 cases, while cytology established the diagnosis of astrocytoma grade II (seven cases), metastases (two cases), gliosis (one case) and benign (four cases). Necrosis of tumour type was observed cytologically in six patients representing glioblastoma (two cases), anaplastic astrocytoma (one case), lymphoma (one case) and normal brain (two cases) histologically. Three cases reported cytologically as benign were primary brain tumour (two cases) and gliosis (one case). One smear of a glioblastoma was insufficient for cytological diagnosis. Cystic lesions were cytologically benign in 17 cases and malignant in three cases. Histology from the cyst wall confirmed the malignant diagnosis in three cases and showed tumour in six more cases, a benign process (two cases), changes induced by radiotherapy for arteriovenous malformation (one case) and insufficient material (one case). In conclusion, cytology from solid brain lesion allows an accurate diagnosis and subtyping of tumours in a majority of cases, and can thus be used to choose type of therapy. In cystic brain tumours, however, examination of the cystic fluid, is often inconclusive and a biopsy from the cyst wall should be performed if there is clinical or radiological suspicion of tumour.
Cytopathology in Slovenia
Authors: Pohar‐Marinšek Ž. , Pogačnik A.
Published: December 2004

Cytopathology started in Slovenia in the early 50s with exfoliative cytology, while fine needle aspiration biopsy (FNAB) was introduced some 10 years later. Today cytopathology is a well accepted diagnostic method in Slovenia and there are currently 20 cytopathological laboratories and 17 cytopathologists. The number of specimens examined in 2001 was 26 230 FNABs, 13 355 exfoliative non cervical and 323 888 cervical smears. FNABs are performed by cytopathologists, by clinical doctors and by radiologists. So far only the cytopathologists have a supervised training period in performing biopsies. In future the same requirement will be obligatory for non pathologists. In four laboratories immunocytochemistry is used as an ancillary technique to morphology and one laboratory is using also flow cytometry for immunophenotyping of lymphomas. The classification system used in Slovenia for reporting the findings in cervical cytology is a combination of Papanicolaou's classification and assessment of dyskariosis. In spite of a long tradition in opportunistic screening for cervical cancer (Cca) an organised screening programme was started late. A four year pilot study, which included one third of the women population of Slovenia, was concluded in 2002 and an organised screening programme was introduced to the whole country in 2003. The incidence rate of Cca in Slovenia has been rising slowly since 1994 and it reached 19.6/100 000 in the year 2000. The mortality rate has remained roughly constant at 5‐7/100 000 for the last 20 years. During the last few years quality assurance measures have been taken for improving the performance in cervical cytology.
Cytology of abnormal nipple discharge: a cyto‐histological correlation
Authors: Lee Wen‐Ying
Published: December 2004

Spontaneous or expressible nipple discharge may occur in palpable and nonpalpable breast lesions. The aim of the study was to evaluate the sensitivity and specificity of nipple discharge cytology in palpable and nonpalpable breast lesions. One hundred and seventy‐four nipple discharge specimens were reviewed, of which 82 had corresponding surgical pathology, including 34 palpable breast lesions and 48 nonpalpable breast lesions. There was good correlation between nipple discharge cytology and concomitant fine needle aspiration (FNA) cytology. Nipple discharge cytology is as specific as concomitant FNA cytology but is slightly less sensitive in detecting papillomas or malignant lesions. The sensitivity and specificity of the nonpalpable and palpable breast lesions were similar. Nipple discharge cytology is very helpful in detecting an underlying breast lesion even if the case has no palpable mass in the breast.
Dipeptidyl peptidase IV expression in thyroid cytology: retrospective histologically confirmed study
Authors: Kholová I. , Ryška A. , Ludvíková M. , Č áp J. , Pecen L.
Published: December 2004

Fine needle aspiration cytology (FNAC) of the thyroid gland is a well‐established method. However, it has inherent limitations, especially in the diagnosis of follicular and oncocytic tumours and in distinguishing between nuclear atypia in colloid goitre with regressive changes and cystic papillary carcinoma. The aim of our study was to evaluate dipeptidyl peptidase IV (DPP IV) as a marker of malignancy in FNAC. We tested 254 thyroid specimens (intraoperative imprint smears) for DPP IV. The sensitivity was 71%, the specificity was 96%, and the diagnostic accuracy was 93%, respectively, with a threshold of 50% of positive cells. To the best of our knowledge it is the largest histologically confirmed study reported in the literature. We suggest the assessment of DPP IV as an adjunct diagnostic marker of malignancy in thyroid specimens suspicious of papillary carcinoma. However, the value of the marker in follicular lesions is very limited.
SM047 immunoreactivity in peritoneal fluids
Authors: McCluggage W. G. , Anderson N. H. , Patterson A. , Stockford J. , Manek S.
Published: December 2004

SM047 is a recently developed monoclonal antibody generated against an ovarian adenocarcinoma cell line. A recent immunohistochemical study has shown that SM047 is strongly expressed in tissue sections of most ovarian serous adenocarcinomas. This study aimed to ascertain whether SM047 staining is of value in cytological preparations of peritoneal fluid. A total of 206 consecutive peritoneal fluids were stained immunocytochemically with SM047, CA125, monoclonal carcinoembryonic antigen (mCEA), Ber‐EP4 and cytokeratins (CK7 and 20). SM047 positivity was present in reactive mesothelial cells in 117 of 141 (83%) benign cases in which these were present. SM047 positive tumour cells were present in 22 of 23 (96%) ovarian serous adenocarcinomas and in small numbers of gastric adenocarcinomas (two of three), mesotheliomas (one of two) and pancreatic adenocarcinomas (one of one). All six colorectal and two breast adenocarcinomas were negative with SM047. Reactive mesothelial cells in all cases were positive with CK7 and in most cases with CA125. They were negative with CEA, Ber‐EP4 and CK20. All adenocarcinomas were positive with Ber‐EP4 and mesothelial cells were always negative. All colorectal adenocarcinomas were positive with CK20. This study shows that SM047 staining may be of value in the diagnosis of an ovarian serous adenocarcinoma in peritoneal fluids. Negative staining helps to exclude a primary ovarian serous adenocarcinoma and is characteristic of colorectal adenocarcinoma. The small numbers of other malignancies in the study precludes a judgement of the value of SM047 staining in these neoplasms. SM047 staining may be useful, as part of a larger panel, in the work up of patients with peritoneal effusions.
Do leaf domatia mediate a plant–mite mutualism? An experimental test of the effects on predators and herbivores
Authors: AGRAWAL ANURAG
Published: December 2004

1. Leaf domatia are tiny structures in leaf vein axils that are widespread among plant taxa and have been described to be typically inhabited by predatory and fungivorous mites. The mutualism hypothesis for the function of leaf domatia predicts that predatory and/or fungivorous mites benefit from having a favourable place to take refuge and reproduce and that plants benefit indirectly from reduced herbivory and/or pathogen attack.

2. The effect of leaf domatia on populations of predatory and herbivorous mites was examined for avocado, Persea americana. In separate experiments, domatia were added to leaves of a variety of avocado plants lacking domatia (Hass) and domatia were blocked on a domatia‐bearing variety (Toro Canyon).

3. In two out of the five experiments conducted, domatia‐bearing plants had significantly higher numbers of predatory mites compared with controls. Although herbivore numbers were consistently lower on plants with domatia than on plants without domatia, in no case did the presence of leaf domatia result in a statistically significant decrease in herbivorous mite populations.

4. These results suggest that domatia may frequently benefit predatory mites, however, indirect effects on herbivorous mites may not commonly exist or may be too difficult to detect.