bluuebunny/crossref_metadata_2025 huggingface dataset:
The role of retinoblastoma protein family in the control of germ cell proliferation, differentiation and survival
Authors: TOPPARI JORMA , SUOMINENF JANNE S. , YAN WEI
Published: May 2003

Retinoblastoma family proteins pRb, p107 and p130 are differentially expressed in the rat testis. They function in specific cell types during testicular development and spermatogenesis, participating in the control of proliferation, differentiation, and survival. Their expression levels and phosphorylation status are modulated during germ cell cycle progression and apoptosis. Hyperphosphorylated states and elevated levels of p107 are correlated with cell cycle progression, whereas hypophosphorylated states and reduced levels are associated with suppression of proliferation and apoptosis in germ cells and Leydig cells. These proteins may also serve as markers of cell cycle status of germ cells during spermatogenesis.
Current views on the pathogenesis of testicular germ cell tumours and perspectives for future research: Highlights of the 5th Copenhagen Workshop on Carcinoma in situ and Cancer of the Testis
Authors: OOSTERHUIS J. WOLTER , LOOIJENGA LEENDERT H. J.
Published: May 2003

This review article highlights the most important contributions presented at the 5th Copenhagen Workshop on Carcinoma in situ and Cancer of the Testis, which was held in Denmark, August 29–31, 2002. The major themes that emerged at the meeting are critically discussed and perspectives for future research in this field are presented.
Terms used to describe urinary tract infections – the importance of conceptual clarification
Authors: LISS PER‐ERIK , ASPEVALL OLLE , KARLSSON DANIEL , FORSUM URBAN
Published: May 2003

Inaccuracies in medical language are detrimental to communication and statistics in medicine, and thereby to clinical practice, medical science and public health. The purpose of this article is to explore inconsistencies in the use of some medical terms: urinary tract infection, bacteriuria and urethral syndrome. The investigated literature was collected from medical dictionaries, textbooks, and articles indexed in Medline®. We found various practices regarding how the medical terms should be defined, and had great difficulty in interpreting the status of the statements under the heading of ‘definition’. The lesson to be learned, besides a reminder of the importance of clearly defined medical concepts, is that it must be explicitly stated whether what is presented as a definition is to be considered as defining criterion, as recognising criterion or as characteristic of the disease entity.
Langerhans cell histiocytosis:
Authors: BANK MICHA I. , RENGTVED PIA , CARSTENSEN HENRIK , PETERSEN BODIL L.
Published: May 2003

Purpose. Langerhans cell histiocytosis (LCH) is a disease with a variable clinical manifestation, being localised (SS) or disseminated (MS). The etiology and pathogenesis of LCH is unknown. It is a proliferative disorder of monoclonal origin, but not necessarily neoplastic. In our study we evaluated histopathological parameters and proliferative activity in LCH. Materials and Methods. Infiltrates from 43 patients with LCH were investigated (nSS=32, nMS=11). We evaluated different histopathological parameters semiquantitatively, demonstrating proliferation using immunohistochemistry for Ki‐67. Results. Overall, the histopathological picture of LCH was heterogeneous. The degree of eosinophilia and presence of necroses was significantly higher in SS‐infiltrates compared to MS‐infiltrates. Mitotic figures were detected in more than half the infiltrates. The Langerhans origin was verified by CD1a. Ki‐67 was highly expressed in all but one infiltrate. Conclusion. The presence of necrosis and the degree of eosinophilia are related to SS‐disease in our study. Ki‐67 expression and the presence of mitotic figures indicate that local proliferation contributes to the accumulation of Langerhans cells. Supported by the histopathological appearance of the lesions and a level of Ki‐67 expression lower than that of neoplastic tissue, we suggest that LCH is a reactive condition, possibly induced by immunostimulation caused by unknown agents.
Increased expression of FLIP, an inhibitor of Fas‐mediated apoptosis, in stomach cancer
Authors: LEE SUG HYUNG , KIM HONG SUG , KIM SU YOUNG , LEE YUN‐SIL , PARK WON SANG , KIM SANG HO , LEE JUNG YOUNG , YOO NAM JIN
Published: May 2003

Despite the cell surface expression of Fas (Apo‐1/CD95), many types of tumor cells, including stomach cancer cells, are resistant to Fas‐mediated apoptosis, indicating the presence of inactivating mechanisms of Fas signaling. Expression of FLICE‐like inhibitory protein (FLIP), one of the inhibitory proteins of Fas‐mediated apoptosis, has been reported in several cancer types, but not in stomach cancer. In the present study, we analyzed the expression of Fas and FLIP in 60 advanced gastric adenocarcinomas by immunohistochemistry using a tissue microarray approach. Immunopositivity (defined as ≥30% of the neoplastic cells) was observed for Fas in 58 (97%) and FLIP in 54 (90%) of the 60 cancers. All of the tumors with FLIP immunostaining also showed Fas immunostaining. Loss of cell surface Fas immunostaining, another mechanism of Fas resistance, was observed in 45 tumors (75%). By contrast, normal gastric mucosal cells showed no or weak expression of both Fas and FLIP. Taken together, these results indicate that increased expression of FLIP is a frequent event in stomach carcinomas, and suggest that for evading apoptosis stomach carcinoma cells in vivo may need FLIP expression, which might contribute to tumor development.
Coronary thrombosis and sudden death after an enteroviral infection
Authors: CALABRESE FIORELLA , BASSO CRISTINA , VALENTE MARIALUISA , THIENE GAETANO
Published: May 2003

We report the case of a 26–year‐old man who died suddenly 9 days after an episode of flu. Microscopic examination of the left anterior descending coronary artery showed an eccentric fibroatheromatic plaque complicated by thrombosis, endothelial erosion and extensive T‐cell and macrophage infiltration. Frozen sections of the thrombotic coronary segment, analysed for different infective agents by polymerase chain reaction (PCR) and reverse transcriptase (RT)‐PCR, showed positive amplification for an enteroviral genome. Enteroviral infection may play an important role in coronary plaque instability and may precipitate thrombotic occlusion.
The relationships between dehydroepiandrosterone sulphate (DHEAS), the intensity of Schistosoma mansoni infection and parasite‐specific antibody responses
Authors: ABEBE F. , BIRKELAND K. I. , GAARDER P. I. , PETROS B. , GUNDERSEN S. G.
Published: May 2003

There are speculations that the puberty‐related hormone dehydroepiandrosterone sulphate (DHEAS) might influence the intensity of infection and immune responses during Schistosoma infections. We studied the relationships between DHEAS, intensity of Schistosoma mansoni infection and humoral immune responses in 135 residents of Ethiopia. Serum levels of eight antibody isotypes against worm and egg antigens were determined by ELISA. DHEAS was measured with an immunoluminometric assay. There was a significant negative correlation between serum levels of DHEAS and intensity of S. mansoni infection. A significant increase in serum levels of DHEAS in the age group 15–19 years was accompanied by a progressive decline in the intensity of infection. Peak level of DHEAS coincided with the lowest intensity of infection in the age group 20–29 years. Multiple regression analysis showed that DHEAS alone had a significant (p<0.0001) negative effect when the effect of age was removed. Age also had a significant (p<0.0001) negative effect on the intensity of infection, after removing the effect of DHEAS. The two predictive variables accounted for 34.4% of the decline in the intensity of infection. Age accounted for 24.9%, whereas DHEAS accounted for 15.2% when the effect of each of the variables was removed. DHEAS had significant negative effects on AWA‐specific IgG (p=0.02) and IgG1 (p=0.018) and SEA‐specific IgG1 (p=0.009), after adjusting for the effect of age.
Phenotypic diversity of oral C. albicans isolated on single and sequential visits in an HIV‐infected Chinese cohort
Authors: SAMARANAYAKE Y. H. , SAMARANAYAKE L. P. , YAU J. Y. Y. , DASSANAYAKE R. S. , LI T. K. L. , ANIL S.
Published: May 2003

HIV‐infected individuals maintain multiple oral C. albicans strains over time that are thought to undergo microevolution in terms of both phenotypic and genotypic features. To study this phenomenon, a 12‐month prospective study was conducted in a cohort of 16 HIV‐infected ethnic Chinese individuals with (A) and without (B) symptoms of oropharyngeal candidiasis to evaluate the phenotype distribution among oral C. albicans isolates during disease progression. Oral rinse samples were obtained and up to five C. albicans colony‐forming units were selected per each visit, during the one year period of multiple visits. The isolates were phenotyped using two commercially available biotyping kits, the API 20C system, API ZYM system, and a plate test for resistance to boric acid. A total of 261 C. albicans strains in group A were differentiated into 67 biotypes, while 42 biotypes were seen amongst the 182 isolates from group B. The major biotypes in the two groups were similar and were in decreasing order of prevalence J1R, J1S, J6S, J6R, J2S, K1S, J10R, K1R, and K6R; 48 different biotypes were seen in group A and 24 in group B, with some uniquely represented in each group, leading to a significant association between the prevalence of the biotypes J1S and J2S and symptomatic candidiasis (p<0.05). Taken together this study illustrates the wide phenotypic spectrum of oral C. albicans associated with HIV‐infection.
GLUT4 expression in human muscle fibres is not correlated with intracellular triglyceride (TG) content. Is TG a maker or a marker of insulin resistance?
Authors: GASTER M. , OTTOSEN P. D. , VACH W. , CHRISTIANSEN H. , STAEHR P. , BECK‐NIELSEN H. , SCHRØDER H. D.
Published: May 2003

We have recently reported a progressive decline in the expression of glucose transporter isoform 4 (GLUT4) from control subjects through obese non‐diabetics to obese type 2 diabetic subjects, indicating that the reduced GLUT4 in slow twitch fibres could be secondary to obesity. In this study we investigate the association of GLUT4 expression with the intracellular triglyceride (TG) content in the same muscle fibres and with plasma lipid parameters. We used histochemistry and stereology to study the relationship between TG content and GLUT4 expression in muscle fibres from obese, obese type 2 diabetic subjects, and young lean controls. TG density was significantly higher in slow compared to fast fibres in all studied subjects (p<0.05). We found an increased TG density in slow twitch fibres of obese diabetic subjects compared to obese (p<0.05) and lean controls (p<0.008). Intracellular TG densities in slow and fast fibres did not correlate with the corresponding GLUT4 density in the same fibres in our study groups (p>0.05). Plasma TG and FFA did not correlate with GLUT4 expression in slow or fast fibres (p>0.05). In conclusion, TG content was increased in diabetic slow fibres with a reduced GLUT4 expression. The GLUT4 expression was not associated with an increased intracellular triglyceride content or with increased plasma FFA levels. Thus, intracellular TG content and circulating FFA may not influence glucose transport directly through GLUT4 expression.
Human sparganosis in Italy
Authors: PAMPIGLIONE SILVIO , FIORAVANTI MARIA LETIZIA , RIVASI FRANCESCO
Published: May 2003

Infections with Spargana, the larvae of Spirometra spp., are rarely found in humans in Europe. So far only six cases have been discussed in the literature, four from Italy and two from France. We here report a new case in a 50‐year‐old workman, a freshwater sports fisherman from Bologna in Northern Italy. The infection manifested as a subcutaneous nodule in the thigh, 2×3 cm in size, slightly painful when compressed, somewhat mobile under the skin, present for 9 months, with recurrent periods of local itchiness associated with redness and slight oedema. The lump was removed surgically. Histological sections of the biopsied material revealed the presence of a sparganum. Drinking water contaminated by copepods, containing procercoid larvae of this parasite, seems to be the medium of infection.
Prevalence of granulocytic Ehrlichia and Borrelia burgdorferi sensu lato in Ixodes ricinus ticks collected from Southwestern Finland and from Vormsi Island in Estonia
Authors: MÄKINEN JOHANNA , VUORINEN ILPPO , OKSI JARMO , PELTOMAA MIIKKA , HE QIUSHUI , MARJAMÄKI MERJA , VILJANEN MATTI K.
Published: May 2003

Altogether, 343 adult and 111 nymphal Ixodes ricinus ticks collected from parks in Turku and suburban and rural islands of the Turku archipelago, Finland, and 100 adult I. ricinus ticks collected from Vormsi Island, Estonia, were included in this study. Using the polymerase chain reaction the ticks were examined for 16S rDNA of the Ehrlichia phagocytophila genogroup and for Borrelia burgdorferi sensu lato recA and flagellin genes. None of the Finnish ticks was found to be infected with E. phagocytophila, whereas 3% of the Estonian ticks were positive for this organism. The rate of Finnish ticks infected with B. burgdorferi sensu lato varied from 0% to 11.6% (mean 5%; 9% for adult and 4% for nymphal ticks). The corresponding rate for Estonian ticks was 15%. Borrelia afzelii was the most common genospecies in both Finnish (2.6%) and Estonian (12%) ticks. B. burgdorferi sensu stricto was detected in 2.0% of the Finnish ticks, but in none of the Estonian ticks. These results suggest that the E. phagocytophila genogroup is very rare in Finnish ticks, although the ticks were collected from an area endemic for Lyme borreliosis. In Estonia, E. phagocytophila is found in ticks and may cause disease.
Chlamydia pneumoniae serology: comparing a commercial enzyme immunoassay and microimmunofluorescence test in patients with cardiovascular disease
Authors: VAINAS TRYFON , DE GRAAF RICK , STASSEN FRANK R. M. , KURVERS HARRIE A. J. M. , GRAULS GERT E. L. M. , KITSLAAR PETER J. E. H. M. , BRUGGEMAN CATHRIEN A.
Published: May 2003

Chlamydia pneumoniae has been associated with cardiovascular disease and the detection of C. pneumoniae antibodies has subsequently challenged many cardiovascular investigators. The micro‐immunofluoresence (MIF) test is considered the gold standard for detection of C. pneumoniae antibodies, but requires a high‐level of expertise for adequate interpretation. We compared an enzyme immunoassay (EIA) with a microimmunofluorescence test for the detection of C. pneumoniae IgG‐ and IgA antibodies in sera of 141 patients with atherosclerosis. The MIF test was read by two independent observers. The interobserver agreement of the MIF test for detection of seropositivity at various cut‐off levels was good for IgG and for IgA. The intra‐test agreement of the EIA was excellent for IgG and IgA. The agreement between EIA and MIF in detection of IgG‐ and IgA antibodies was adequate at low but not at high titer levels. At low titer levels, the sensitivity, specificity, positive and negative predictive value of EIA compared to the MIF test was sufficient. The sensitivity of the EIA increased, improving the agreement with the MIF at high titer levels by retesting sera with elevated titers at higher pre‐dilutions. In conclusion, the EIA shows sufficient agreement with the MIF test in the detection of C. pneumoniae seropositivity. Therefore, the EIA is a practical alternative to the MIF in the detection of C. pneumoniae antibodies in patients with cardiovascular disease, bearing in mind that the sensitivity of the EIA depends on the antibody titer.
Modulation of the pathology of late xenograft rejection by PAF‐antagonist UR‐12670 in the hamster‐to‐rat liver xenotransplant model
Authors: GINESTÀ MIREIA M. , MOLLEVÍ DAVID G. , SERRANO TERESA , BAS JORDI , MESTRE MARIONA , RIBAS YOLANDA , FIGUERAS JOAN , JAURRIETA EDUARDO
Published: May 2003

PAF antagonists have been used in xenotransplantation to alleviate the pathogenesis of hyperacute rejection. This study evaluated the ability of the PAF antagonist UR‐12670 to improve graft function in late xenograft rejection (LXR) in an orthotopic liver xenotransplantation model, and the involvement of PAF (platelet activating factor) in this type of rejection. The recipients of a hamster xenograft received standard immunosuppression (tacrolimus 0.2 mg/kg/30 days, MMF 25 mg/kg/8 days). Study groups: group A, without UR‐12670, group B, UR‐12670 (20 mg/kg/8 d) and group C, continuous administration of UR‐12670 (20 mg/kg/d). Serum levels of xenoantibodies were evaluated by flow cytometry and tissue deposits by immunofluorescence. Immunoblot and indirect immunofluorescence assessed specificity of xenoantibodies. Conventional histology was performed. Continuous administration of UR‐12670 improved the histological pattern of liver xenografts, especially necrosis, loss of hepatocytes, hemorrhage, sinusoidal congestion and lymphocyte infiltration. There was not a shift in specificity of xenoantibodies at different times posttransplantation, as demonstrated by immunoblotting and indirect immunofluorescence. UR‐12670 administration had a beneficial effect on graft function and considerably improved the histopathological pattern, but it failed to induce tolerance after withdrawal of immunosuppression. UR‐12670 had an immunomodulatory effect on cellular response but not on antibody production. There was not a change in the specificity of xenoantibodies produced at LXR compared with pretransplant antibodies.
Immunohistochemical analysis of Smac/DIABLO expression in human carcinomas and sarcomas
Authors: YOO NAM JIN , KIM HONG SUG , KIM SU YOUNG , PARK WON SANG , PARK CHO HYUN , JEON HAE MYUNG , JUNG EUN SUN , LEE JUNG YOUNG , LEE SUG HYUNG
Published: May 2003

Second mitochondria‐derived activator of caspases (Smac/DIABLO) is released from mitochondria into the cytosol during apoptosis, promoting caspase activation by neutralizing the inhibition of inhibitor of apoptosis proteins (IAPs) on caspases. Alteration of apoptosis is essential for cancer development, and cancer cell death by radiation and chemotherapy is largely dependent upon apoptosis. In this study, archival tissues of 100 carcinomas and 50 sarcomas from various origins were analyzed by immunohistochemistry for the expression of Smac/DIABLO. Smac/DIABLO immunoreactivity was seen in 62 of 100 (62%) carcinomas, including 42 of 60 stomach carcinomas, 7 of 10 colorectal carcinomas, 4 of 10 lung carcinomas, 7 of 10 ovarian carcinomas, and 2 of 10 prostate carcinomas. Smac/DIABLO is expressed in 11 of 50 (22%) sarcomas, including 2 of 8 malignant schwannomas, 5 of 11 rhabdomyosarcomas, 2 of 7 malignant fibrous histiocytomas, 1 of 6 leiomyosarcomas, 0 of 8 angiosarcomas, 0 of 8 liposarcomas, and 1 of 2 Ewing's sarcomas. These data demonstrated that Smac/DIABLO expression levels vary depending on the individual cancer types. Furthermore, the present study showed that many human cancers do not express Smac/DIABLO, and suggest that lack of Smac/DIABLO expression in the cancer cells may inhibit apoptosis, thereby promoting their survival.
Recombinant HpaA purified from Escherichia coli has biological properties similar to those of native Helicobacter pylori HpaA
Authors: LUNDSTRÖM ANNELI M. , BÖLIN INGRID , BYSTRÖM MONA , NYSTRÖM SUSANNE
Published: May 2003

The aim of this study was to recombinantly produce and purify Helicobacter pylori adhesin A (HpaA) from Escherichia coli and compare it to purified native H. pylori HpaA, for potential use as a vaccine antigen. The hpaA gene was cloned from H. pylori, transferred to two different expression vectors, and transformed into E. coli. Expression of rHpaA was analysed by immunoblot, inhibition ELISA, and semi‐quantitative dot‐blot. Using affinity chromatography, rHpaA was purified from E. coli and native HpaA from H. pylori. The binding of both purified proteins to sialic acid was analysed and antibody titres to native and rHpaA were compared after intraperitoneal immunisation of C57/Bl mice. The rHpaA protein was highly expressed in E. coli from both vectors. Purified recombinant and native HpaA bound similarly to fetuin but also to the non‐sialylated asialofetuin. Both native HpaA and rHpaA induced comparable amounts of specific antibodies in serum after immunisation and they were identical in double immunodiffusion. In conclusion, rHpaA was successfully produced in E. coli. Purified rHpaA showed biological properties similar to those of native HpaA isolated from H. pylori and may therefore be further used as an antigen in the development of a vaccine against H. pylori infection.
Routine genotyping of human papillomavirus samples in Denmark
Authors: JOHNSON THOMAS , BRYDER KARIN , CORBET SYLVIE , FOMSGAARD ANDERS
Published: May 2003

In order to examine a sensitive unbiased consensus PCR with routine sequencing for HPV typing, we analysed Danish male and female patients suspected of having an HPV infection. We used the well‐characterised nested PCR setting with MY09/MY11 and GP5+/GP6+ primers, followed by routine cycle sequencing. Of 1,283 clinical samples from female patients based on suspected HPV infection, we found 379 (29%) negatives and 894 (70%) positives. Samples containing >5000 HPV copies/ml were genotyped by sequencing. Of the 552 HPV genotyped samples from women >15 years of age, 398 were characterised as high‐risk types and the remaining 154 as low‐risk types. The most commonly found high‐risk types were HPV‐16, HPV‐31, HPV‐33, HPV‐18, HPV‐58, and HPV‐52, and the most commonly found low‐risk types were HPV‐6, HPV‐53 and HPV‐11. In addition, we observed that other typing assays could not perform as sensitively or accurately as the nested PCR/cycle sequencing method used in this study. For instance, 87 out of 552 genotyped samples could not have been typed correctly in the Hybrid Capture II assay. Of these 87 samples, 46 (53%) were considered as high‐risk types.
Activation of the respiratory burst by Pneumocystis carinii
Authors: LAURSEN ALEX L. , OBEL NIELS , HOLMSKOV UFFE , JENSENIUS JENS C. , ALIOUAT EL MOUKHTAR , ANDERSEN PAUL L.
Published: May 2003

The effect of opsonization of Pneumocystis carinii with different antibody classes, complement, mannan‐binding lectin (MBL), and lung surfactant protein D (SP‐D) on respiratory burst activation was studied. Antibodies were obtained by affinity chromatography, complement from a hypogammaglobulinaemic patient, and phagocytic cells from blood donors. Respiratory burst activation was measured by chemiluminescence (CL). With freshly isolated neutrophils the combination of antibodies and complement but not antibody alone, had opsonizing properties. With neutrophils cultured for 20 h, however, IgG increased the CL response. In macrophages P. carinii opsonized with IgG alone induced a CL response proportional to the antibody titre used. With IgA an effect, albeit lower, was also seen, whereas IgM alone was inefficient. The combined effect of antibodies and complement increased the response significantly for all three antibody classes, IgG and complement giving the largest response. Binding of MBL to P. carinii and Candida albicans was demonstrated; however, only the former stimulated activation of the respiratory burst. SP‐D did not bind to either microorganism and had no effect on the respiratory burst. It is concluded that IgG, IgA and complement are important opsonizing factors in infections involving P. carinii. The relative importance varies with the type of phagocytic cell studied.
Myoepithelioma of the vulva
Authors: FUKUNAGA MASAHARU
Published: May 2003

The histologic diagnosis of myoepithelioma is often problematic. We here describe a case of myoepithelioma, composed exclusively of neoplastic myoepithelial cells, in the vulva of a 52‐year‐old female. The vulva is a very rare site for this neoplasm. A subcutaneous tumor measuring 3.0×2.5×2.0 cm displayed a multinodular growth pattern. Histologically, it was characterized by epithelioid, trabecular, cord, solid, or reticular arrangements of tumor cells and markedly hyalinized stroma. The tumor cells were large and polygonal with eccentrically located round to oval nuclei with prominent nucleoli and eosinophilic cytoplasm. Some cells had clear cytoplasm. Moderate cellular atypia was seen and there were 4 mitotic figures per 10 high‐power fields. No ductal architecture was found and there were no areas of chondroid or osseous differentiation. There was no destructive invasive growth. Immunohistochemically the tumor was positive for vimentin, epithelial membrane antigen, wide keratin, alpha‐smooth muscle actin, S‐100 protein, and glial fibrillary acidic protein. The patient was well and free of disease at 6 months. This neoplasm should be distinguished from other epithelial and mesenchymal neoplasms as it shows a different clinical behavior.
ICAM‐1 and β3 integrin immunoexpression in malignant melanoma cells: can they be used as additional predictors?
Authors: HARITOPOULOS KONSTANTINOS N. , LAZARIS ANDREAS C. , KAVANTZAS NIKOLAOS , TSELENI‐BALAFOUTA SOFIA , THOMOPOULOU GEORGIA , ARONI KYRIAKI
Published: May 2003

Malignant melanoma usually progresses from the intraepidermal microenvironment through a distinct radial growth phase, in which malignant potential cannot always be accurately evaluated, to invasion of the dermis (vertical growth phase) and metastasis. During these stages malignant cells interact with each other and with the extracellular matrix. This interaction is mediated by cell surface adhesion molecules such as the β3 integrin subunit and ICAM‐1. Our aim was to investigate whether the expression of these two molecules is associated with the various histopathologic prognosticators commonly evaluated in malignant melanoma. Using a standard three‐step immunoperoxidase technique we evaluated the above molecules' expression in a documented series of 66 cutaneous malignant melanomas. Forty‐five were superficial spreading melanomas, including 18 in mixed growth phase. Positive immunoreaction was estimated by image analysis. ICAM‐1 immunopositivity status was significantly more frequent among malignant melanomas of the nodular type (p=0.0001), and was associated with the vertical growth phase, Breslow thickness of >0.77 mm, and with evident lymphocytic infiltration. β3 integrin immunopositivity showed similar results in certain respects; it was more frequently detected in superficial spreading melanomas in which vertical growth had developed (p=0.002) and in cases with regression. There appears to be an association of these molecules with histopathologic features that predict increased tumorigenicity of malignant melanocytes.
Validation of the use of proliferation markers in canine neoplastic and non‐neoplastic tissues: comparison of KI‐67 and proliferating cell nuclear antigen (PCNA) expression versus in vivo bromodeoxyuridine labelling by immunohistochemistry
Authors: ZACCHETTI A. , VAN GARDEREN E. , TESKE E. , NEDERBRAGT H. , DIERENDONCK J. H. , RUTTEMAN G. R.
Published: May 2003

In order to evaluate the suitability of Ki‐67 and proliferating cell nuclear antigen (PCNA) for determination of proliferative activity, the immunohistochemically determined nuclear expression of these antigens in canine non‐neoplastic and neoplastic tissues was compared with the results of in vivo bromodeoxyuridine (BrdU) labelling, which – by measurement of the fraction of S‐phase cells – is considered as the standard in the analysis of proliferative activity. The samples investigated consisted of non‐neoplastic mammary and lymphoid tissues, and of benign and malignant (primary/metastatic) mammary tumours, and malignant lymphomas. Great regional heterogeneity prevented determination of an overall labelling index (LI) in normal lymphoid tissues. In the remaining combined group of samples, LI values were significantly ranked in the order PCNA>Ki‐67>BrdU. However, the correlation of Ki‐67 or PCNA as compared to BrdU LI values was only moderate in the combined group [approximately 0.5, Spearman rank test] as well as in most subgroups, whilst it was very poor in the group of primary mammary cancers. These observations indicate that Ki‐67 or PCNA LIs as markers of proliferation do not evenly match in vivo BrdU labelling.
Clinical importance of vascular endothelial growth factor (VEGF) for papillary thyroid carcinomas
Authors: KILICARSLAN AKKAYA BAHAR , OGUS MEHMET , ARICI CUMHUR , PESTERELI H. ELIF , CAKIR MEHTAP , KARPUZOGLU GULTEN
Published: May 2003

Vascular endothelial growth factor (VEGF) is a major regulator of angiogenesis and may be produced by some cancer cells. Several recent reports have documented that increased expression of VEGF is associated with risk of recurrence or decreased recurrence‐free survival in papillary thyroid cancers (PTC). The aims of this study were to determine whether immunohistochemical expression of VEGF is related to local and distant recurrence of PTC and to evaluate the relationship between hypervascularization and VEGF expression in papillary thyroid carcinomas. VEGF expression was examined immunohistochemically in 48 papillary carcinomas. Ten normal thyroids were used as controls. Patients were followed for 61.7 (range 24–143) months. Twelve of the patients had local and distant recurrences. VEGF immunostaining, blinded for clinicopathological data, was evaluated semiquantitatively by two pathologists. The difference between the recurrent (n:12) and nonrecurrent (n:36) carcinomas was statistically significant (p:0.001). VEGF expression was also stronger in papillary thyroid carcinomas than in normal thyroid tissues. The mean microvascular densities were significantly higher than in normal thyroid tissues. These data indicate that VEGF staining is strongly associated with increased frequency of local and distant recurrence in PTC and that the immunohistochemical profile of the expression may be used as a marker for predicting which tumors have metastatic potential.
Assessment of HER‐2/neu overexpression and/or gene amplification in breast carcinomas: should in situ hybridization be the method of choice?
Authors: SAUER TORILL , WIEDSWANG GRO , BOUDJEMA GHANIA , CHRISTENSEN HANNE , KÅRESEN ROLF
Published: May 2003

Aims: Since the release of Herceptin®, pathology laboratories have been requested to test breast carcinomas for HER‐2/neu overexpression and/or gene amplification. Standardized IHC and FISH are mandatory in order to get reliable results, but there are problems even with standardized procedures. We decided to evaluate the two methods to determine which, or possibly if both, should be the primary investigation method(s).

Methods and Results: The material consisted of 215 primary invasive breast carcinomas with complete clinical follow‐up of 15 years. HER‐2/neu protein expression was determined for all specimens, whereas FISH for assessing HER‐2/neu gene signal number was done in 165 cases. IHC was double‐checked with two or three different antibodies in 35 tumours, including all cases with discrepancies between IHC and FISH. Among these, there were discrepancies in a third. IHC overexpression of HER‐2/neu was found in 13% and gene amplification in 18%. Discordance between IHC and FISH was found in 11 cases (8%). Five tumours were IHC+/FISH− and six were IHC−/FISH+. IHC and FISH positive cases as well as FISH only positive tumours had the same prognosis respecting survival. Tumours with >2 but ≤4 HER‐2 gene signals per nucleus had the same survival as cases with >4 gene signals per nucleus. In contrast, cases with IHC overexpression without gene amplification had a prognosis similar to that of IHC−/FISH− tumours.

Conclusions: From our data, it seems to be more important to assess HER‐2/neu gene amplification than IHC overexpression. Failure to detect FISH‐amplified (IHC‐negative) cases would have an adverse effect on the survival of these patients. On the other hand, IHC overexpression tumours without gene amplification appear to belong to a better prognostic group, and failure to detect them would probably not have a negative effect on the survival of these women. Even though FISH is a more complex and expensive procedure, it should be considered the method of choice for primary assessment of HER‐2/neu status in breast cancer patients.
Oral and general health‐related quality of life with conventional and implant dentures
Authors: Heydecke Guido , Locker David , Awad Manal A. , Lund James P. , Feine Jocelyne S.
Published: May 2003

Abstract – Implant overdentures and conventional prostheses have been compared in several trials using a variety of functional and oral health‐related quality of life (OHQOL) outcomes. In this paper, we describe the impact of implant overdentures on general and OHQOL in seniors.

Objectives: To compare the oral health‐related and general quality of life of seniors (aged 65–75 years) who received either mandibular implant overdentures or conventional dentures.

Methods: Sixty edentulous patients were recruited. Thirty received mandibular overdentures retained by two implants (IOD) and a conventional maxillary denture, the other 30 subjects received new maxillary and mandibular conventional complete dentures (CD). All completed the 20‐item version of the Oral Health Impact Profile (OHIP‐20) before treatment, then at two and 6 months after delivery of the dentures. The SF‐36 general health questionnaire was completed at baseline and 6 months only.

Results: Pretreatment and 6‐month data from 55 subjects were analyzed. Those who received the IODs had significantly better OHIP‐20 total scores at 6 months. Results for IOD subjects were also superior in the functional limitation, physical pain, physical disability and psychological disability subscales. While no significant between group difference was found on the SF‐36 health survey, significant pre–post‐treatment differences within the IOD group were detected for the role emotional, vitality and the social function scales.

Conclusions: Mandibular overdentures retained by two implants provide elderly patients with better OHQOL. General health‐related quality of life improved in the implant group.
Cost‐effectiveness of different caries preventive measures in a high‐risk population of Swedish adolescents
Authors: Oscarson N. , Källestål C. , Fjelddahl A. , Lindholm L.
Published: May 2003

Abstract –

Objectives: A total of 3373 12‐year‐olds agreed to participate in an intervention study evaluating different caries preventive measures. The study, titled ‘Evaluation of caries preventive measures’, was performed between 1995 and 1999 at 26 dental health clinics throughout Sweden. At the start of the study, the subjects were classified as individuals at high or low risk of developing caries. The high‐risk group consisted of 1165 subjects. The children in the high‐risk group were randomly assigned to one of four preventive programs. The programs represent a step‐wise increase in fluoride content, contact with dental personnel and cost. The aim of the present cost‐effectiveness analysis (CEA) study performed from a societal perspective is to compare costs and consequences of caries preventive programs in a caries high‐risk population. By ‘costs’ is meant both treatment costs and costs contributed by the patient and the patient's family. Costs contributed by patients and their families consist of out‐of‐pocket expenses, transportation costs, and time. Conclusions are that it is important to consider the perspective from which a study is carried out. Costs contributed by the patient and the patient's family have a high impact on total costs for children and younger adolescents but decrease with time as the adolescents get older. The present study shows an incremental cost‐effectiveness of 2043 SEK (8.54 SEK = US$ 1, December 1999) per averted decayed enamel and dentine missing and filled surface (DeMFS), of which treatment costs represent 1337 SEK using the unit cost for a nurse. This means a yearly cost of approximately 334 SEK.
Caries incidence in permanent first molars after discontinuation of a school‐based chlorhexidine‐thymol varnish program
Authors: Baca Pilar , Junco Pilar , Bravo Manuel , Baca Adela P. , Muñoz M. José
Published: May 2003

Abstract –

Objectives: To determine whether the cessation for 3 years of a 24‐month program of chlorhexidine‐thymol varnish applications would affect caries incidence in the first permanent molars of a population of schoolchildren of middle and lower‐middle socioeconomic level.

Methods: Two groups of 6–7‐year‐old schoolchildren, randomized by school‐class, were followed up in a clinical trial. One group received applications of chlorhexidine‐thymol varnish every 3 months and the other group acted as controls. The program ended after 24 months and its effects were evaluated. Three years later, 55.5% of the schoolchildren were re‐examined and the caries increments were documented.

Results: At the end of the 24‐month program, the treated children had significantly fewer decayed and filled surfaces in permanent molars (lower DFS index) versus the controls. At 3 years after the discontinuation of the program, this difference had disappeared; there were no differences in the incidence of decayed, missing and filled surfaces (DMFS) index in permanent molars between the treated children and the controls.

Conclusion: The cessation for 3 years of a 3‐month program of chlorhexidine‐thymol varnish applications resulted in a nonsignificant increase in the prevalence of dental caries in the permanent first molar.
Fluoride intake by Brazilian children from two communities with fluoridated water
Authors: Paiva Saul M. , Lima Ynara B. O. , Cury Jaime A.
Published: May 2003

Abstract –

Objectives: To determine total daily fluoride intake by young children from two communities in a developing country.

Methods: Fluoride intake from diet and dentifrice was determined for 71 Brazilian children, aged 19–38 months, living in two communities with fluoridated water (0.6–0.8 ppm). The children from Piracicaba attended a full‐time day care centre but those from Ibiá did not. Fluoride ingested during tooth brushing was determined, and ‘duplicate‐plate’ samples of all foods and beverages ingested during a 2‐day period were collected from which fluoride for analysis was extracted by hexamethyldisiloxane (HMDS) microdiffusion. The amount of fluoride ingested (mg F/kg body weight/day) from the diet and dentifrice and the combined fluoride intake were calculated. A limit of 0.05–0.07 mg F/kg body weight/day was considered as the safe threshold for fluoride exposure.

Results: The children from Ibiá had lower amounts of fluoride in their diets than those from Piracicaba (P < 0.05); no differences in the amount of fluoride ingested from dentifrice were found between the communities. In both communities, the daily fluoride intake from dentifrice was higher than that from the diet (P < 0.05). Most of the children from both communities were exposed to a combined dose (diet + dentifrice) of fluoride above the risk threshold for dental fluorosis.

Conclusion: The data suggest that fluoride intake from diet depends on living conditions, and measures should be implemented to reduce the fluoride intake of these Brazilian children.
The self‐assessed oral health status of individuals from White, Indian, Chinese and Black Caribbean communities in South‐east England
Authors: Newton J. T. , Corrigan M. , Gibbons D. E. , Locker D.
Published: May 2003

Abstract –

Objectives: To determine the level of self‐assessed oral symptoms and the impact of such symptoms among individuals from four ethnic groups resident in South‐east England and the relationship between self‐assessed oral health status, age, gender, employment status, educational level and ethnicity.

Method: Cross‐sectional survey of a convenience sample of 366 individuals drawn from four ethnic groups.

Measures: Subjective Oral Health Status Indicators (SOHSI).

Participants: Individuals were recruited through community groups. All participants self‐classified their ethnicity. Only completed questionnaires from participants categorising themselves as White, Black Caribbean, Chinese or Indian were included in the data analysis.

Findings: Univariate statistical analysis revealed significant differences between ethnic groups in all but one of the SOHSI scales. Age and ethnicity (in particular membership of the Chinese community) emerged as significant predictors of SOHSI scale scores.

Conclusions: Within the limitations imposed by convenience sampling, it has been found that differences exist among four ethnic groups in the UK in their reporting of self‐assessed oral health status. Ethnicity and age, in particular, predict the reporting of self‐assessed oral symptoms and the impact of such symptoms.
Reporting on adverse reactions to dental materials – intraoral observations at a clinical follow‐up
Authors: Lygre Gunvor Bentung , Gjerdet Nils Roar , Grønningsæter Arne Geir , Björkman Lars
Published: May 2003

Abstract –

Objectives: A national reporting system designed to monitor adverse reactions to dental materials was established in Norway in 1993. The activities have also included clinical examination of patients with suspected reactions to dental materials. The ongoing activities are coordinated by the Dental Biomaterials Adverse Reaction Unit at the University of Bergen. The reporting procedure is based on voluntary spontaneous reporting by dentists and physicians. The reports could be based on subjective symptoms or objective findings, or both. The aim of the present study was to compare reported objective intraoral findings with those found during examination at the unit.

Methods: Reported reactions were compared with clinical findings obtained following dental and medical examination at the unit. From 1993 to 1999, a total of 899 reports were received while 253 patients were referred and examined at the unit.

Results: The reports on patients who were examined at the unit involved mainly reactions related to amalgam fillings (84%), metals in fixed dentures (11%), resin‐based materials and cements (4%), materials used in removable dentures (2%), and endodontic materials (2%). Edema, lichenoid reactions, ulcers/vesicles, erythema, and atrophy were found in 80 patients during the examination at the unit. For 35 of these patients, the intraoral findings at the unit were also given in the reports. For another 45 patients, objective intraoral signs of reactions were found upon examination at the unit, but these findings had not been reported.

Conclusion: A spontaneous reporting system is a cost‐effective method for monitoring intraoral reactions associated with dental materials. Considering the increasing number and complexity of these materials, there appears to be a need for continuous validation of reports by a speciality unit. In order to receive more accurate information about the adverse reactions, it would be advisable that the reporting forms include more detailed guidance regarding signs of reactions that practitioners should be on the look out for and consider.
A comparison of dental health care attitudes in the Netherlands in 1985, 1995, and 2001
Authors: Bos Annemieke , Hoogstraten Johan , Prahl‐Andersen Birte
Published: May 2003

Abstract –

Objectives: The aim of the present study was to re‐establish and update empirical data obtained in 1985 and 1995 using the dental attitudes questionnaire (DAQ). In 1984, this instrument for assessing oral health care attitudes was presented by Stockwell and Banting. The DAQ has six content scales: cynicism, health concern, motivation, oral function, social aesthetic and susceptibility, and two validity scales, halo and infrequency.

Methods: The DAQ was completed in a similar setting using similar subjects in 1985, 1995, and 2001. Subjects were first‐year psychology students who participated for course credit.

Results: A high level of agreement among respondents was found in their ranking of attitudinal factors. The mean scores on most subscales were lower in 1995 and 2001 than in 1985. In 2001, respondents scored higher on the subscale ‘motivation’, and lower on the subscales ‘cynicism’ and ‘social aesthetic’ than subjects in 1995.

Conclusion: Some changes have occurred in dental health care attitudes as measured by the DAQ during the intervals between the three studies. Subjects in 2001 showed less suspicion regarding the motives of dental health care professionals and downplayed more need for regular dental checkups and oral hygiene than subjects in former years. The psychometric qualities of the DAQ were considered to be satisfactory.
Caries and micronutrient intake among urban South African children: a cohort study
Authors: MacKeown Jennifer Margaret , Cleaton‐Jones Peter Eiddon , Fatti Paul
Published: May 2003

Abstract –

Objective: To report on associations between caries and micronutrient intake among a ‘true cohort’ group of 5‐year‐old urban black South African children.

Methods: The study sample was a true cohort that had nutrition as well as dental information for 1991 and 1995 (n = 259). Micronutrient intake and dental caries associations were examined with SAS using the linear logistic analysis and a critical level of statistical significance of P < 0.05.

Results: Of the 21 micronutrients investigated, vitamin B12, riboflavin, magnesium and biotin were individually significantly associated with caries incidence, but taken together only magnesium was significant.

Conclusions: The association of micronutrient intake with caries was weak, isolated and not clinically relevant. Micronutrient intake was not an indicator of the presence or absence of caries among the children studied.
Fluoride intake from foods, beverages and dentifrice by children in Mexico
Authors: Martínez‐Mier E. Angeles , Soto‐Rojas Armando E. , Ureña‐Cirett José L. , Stookey George K. , Dunipace Ann J.
Published: May 2003

Abstract –

Objectives: This investigation monitored fluoride ingestion in Mexican children who were susceptible to developing dental fluorosis.

Methods: Total fluoride intake, from dietary and toothpaste samples, was determined in 15–36‐month‐old children from Mexico City and Veracruz, Mexico. A duplicate plate technique was used. Plasma fluoride levels were also determined in this group of children.

Results: The children ingested a mean (±SD) of 0.20 ± 0.08 and 0.18 ± 0.07 mg fluoride/kg/day, in Mexico City and Veracruz, respectively. There was no statistically significant difference between the fluoride ingested by children in the two cities (P > 0.9). Plasma from children in Mexico City and Veracruz contained a mean of 1.30 ± 0.81 and 0.87 ± 0.72 µmol fluoride/l, respectively, and these values were not significantly different.

Conclusions: Our results lead to the conclusion that mean fluoride ingested from the combination of foods and beverages was within the proposed safe threshold for fluoride intake of 0.05–0.07 mg F/kg/day. Most of the fluoride intake by these children was derived from the ingestion of fluoridated toothpaste. When all sources of ingested fluoride were added and total fluoride intake was calculated, the children, both in Mexico City and Veracruz, were ingesting amounts of fluoride well above the upper limits of the proposed safe threshold for fluoride intake.