Significance of transcriptionally-active high-risk human papillomavirus in sinonasal squamous cell carcinoma: Case series and a meta-analysis.

Sinonasal cancers represent a highly heterogeneous group of head and neck cancers, for which etiological and prognostic significance of high-risk human papillomavirus (HPV) infections has not yet been conclusively established. We investigated the presence of transcriptionally-active high-risk HPV in a series of 34 sinonasal squamous cell cancer (SNSCC) cases and evaluated the effect of transcriptionally-active HPV on the overall survival. In addition, we performed a meta-analysis of previously published studies, including this study, to summarize the prevalence of HPV positivity across histological subtypes of SNSCC. The presence of transcriptionally-active HPV was detected by HPV mRNA using the polymerase chain reaction (PCR) or in situ hybridization (ISH). p16 expression was evaluated as a surrogate marker for transcriptionally-active HPV infection by immunohistochemistry (IHC), the presence of high-risk HPV DNA was tested by PCR and the HPV genotypes were determined by sequencing of PCR amplicons. Transcriptionally-active HPV infections were found in ~25% of the SNSCC cases. The role of HPV infection in keratinizing SNSCC may be higher than previously reported (~32% in our study vs. ~0-6.3% in all other studies). Patients with transcriptionally-active HPV-positive SNSCCs were more likely to be diagnosed at earlier stages (p<0.05) and displayed better mean overall survival, although the difference between HPV-positive and HPV-negative groups was not statistically significant. In contrast to other non-oropharyngeal squamous cell carcinomas (non-OPSCCs) of the head and neck, in SNSCCs, p16/IHC and p16/IHC+HPV DNA displayed high specificity as surrogate markers of transcriptionally-active HPV infections. However, p16/IHC may have significantly lower sensitivity as a surrogate marker of transcriptionally-active HPV in SNSCCs compared to OPSCCs. Furthermore, in our group of SNSCCs, all cases positive for high-risk HPV DNA by PCR were also transcriptionally-active (causative) infections with positive HPV mRNA by ISH. Our results imply a possible different role of HPV-mediated carcinogenesis of squamous cell epithelium in oropharyngeal and sinonasal sites with the latter displaying a lower proportion of causative HPV infections; nevertheless, most cases positive for high-risk HPV DNA, p16/IHC or combination thereof were also found positive for transcriptionally-active HPV. The prognostic significance of HPV status in SNSCCs remains inconclusive and future studies should investigate the presence of transcriptionally-active HPV by direct HPV testing.

Significance of bizarre cells in cervical screening liquid-based cytology: A prospective study of 15 cases.

OBJECTIVE: The aim of this study was to assess the significance of bizarre cells (cells of squamous origin with a superficial squamous cell-type cytoplasm and characterised by multinucleation that produces bizarre nuclear shapes) in liquid-based cytology (LBC) Papanicoaou (pap) smears with clinical and histological follow-up correlation. METHODS: Fifteen patients, all with LBC samples containing bizarre cells, were identified in routine ThinPrep® LBC workload. HPV testing was performed in each case using residual LBC material. Cytological-histological correlations were reviewed. RESULTS: All 15 LBC samples contained bizarre cells and tested positive for high-risk HPV types. Ten of the 15 cases were identified as atypical squamous cells - cannot exclude an HSIL (ASC-H) with secondary diagnosis of low-grade squamous intraepithelial lesion (LSIL), while five cases were identified as high-grade squamous intraepithelial lesion (HSIL), and a subsequent biopsy was recommended. Additionally, 13/15 cases underwent cone biopsy or hysterectomy within 1-11 months, of which 10 showed histologically confirmed HSIL end-points. LSIL was present in three cases. Bizarre cells were identified in the HSIL epithelium of five cone biopsies. CONCLUSIONS: Identification of bizarre cells in LBC is straightforward and may facilitate diagnosis. The cytology of bizarre cells is associated with HSIL in cone biopsies. We recommend assigning LBC samples containing bizarre cells as ASC-H with secondary diagnosis of LSIL.

Liver tuberculoma.

BACKGROUND: Liver tuberculosis is a fairly rare manifestation of extra-pulmonary tuberculosis. We distinguish several forms of liver affection by tuberculosis. One of these is liver tuberculoma, the incidence of which is quite rare. The authors present a case of liver tuberculoma as an occupational disease. CASE REPORT: A 63-year-old veterinary doctor, who was diagnosed through a polymerase chain reaction with liver tuberculosis, was treated unsuccessfully with anti-tuberculosis drugs for a period of 8 months. After an earlier relapse of the focus in the liver it grew again and created an abscess (80 x 65 x 80 mm), together with a second satellite focus (20 mm). The patient was therefore indicated for a resection of 3 segments of the right liver lobe. The resection was without complications. The polymerase chain reaction, together with histology, proved the presence of a mycobacterium tuberculosis complex. Three year after the surgery, the patient is completely recovered, without any manifestations of the disease. CONCLUSION: Liver resection for liver tuberculoma is indicated in case of progression of the finding and long-term unsuccessful treatment with anti-tuberculosis drugs. It is a safe method with very good long-term results (Fig. 2, Ref. 12).

Renal angiomyoadenomatous tumor: morphologic, immunohistochemical, and molecular genetic study of a distinct entity.

We present a series of a distinct tumorous entity named renal angiomyoadenomatous tumor (RAT). Five cases were retrieved from the consultation files of the authors. Histologic and immunohistochemical features were evaluated. Sequencing analysis of coding region of the VHL gene was carried out in all cases. The tumors were composed of admixture of an epithelial clear cell component and prominent leiomyomatous stroma. Epithelial cells formed adenomatous tubular formations endowed with blister-like apical snouts. All tubular/glandular structures were lined by a fine capillary network. The epithelial component was positive for epithelial membrane antigen, CK7, CK20, AE1-AE3, CAM5.2, and vimentin in all cases. In all analyzed samples, no mutation of the VHL gene was found. RAT is a distinct morphologic entity, being different morphologically, immunohistochemically, and genetically from all renal tumors including conventional clear cell carcinoma and mixed epithelial and stromal tumor of kidney.

Mucinous tubular and spindle cell carcinoma with Fuhrman nuclear grade 3: a histological, immunohistochemical, ultrastructural and FISH study.

Mucinous tubular and spindle cell carcinoma (MTSCC) of the kidney generally shows low nuclear grade. MTSCC with high nuclear grade is relatively rare. In this article, we report two cases of MTSCC with Fuhrman grade 3. One case occurred in a 57-year-old Japanese female and the second case in a 49-year-old Caucasian female. Histologically, the tumors were composed of neoplastic cells with cuboidal or columnar and spindle morphology, and Fuhrman nuclear grade 3. The myxoid stroma was also observed. This stroma was positive for Alcian blue stain. Immunohistochemically, neoplastic cells of both cases were positive for AMACR, but negative for CD10 and RCC Ma. Ultrastructurally, tumorous cells of one case contained numerous mitochondria. In FISH analysis, many neoplastic cells of both cases demonstrated monosomy of chromosomes 15 and 22 and disomy of chromosomes 7 and 17. One of the two patients died of respiratory failure due to pleuritis carcinomatosa 48 months postoperatively. Finally, the pathologist should recognize that high grade MTSCC exists despite its rare frequency. FISH analysis may be helpful in establishing the diagnosis of this entity. Furthermore, we present the first report of a patient with MTSCC dying of distant metastasis.

[Epidemiological characteristics of diabetes mellitus in Slovakia, 1992-2002]. / Epidemiologicke charakteristiky diabetes mellitus na Slovensku v rokoch 1992 az 2002.

UNLABELLED: Diabetes mellitus (DM) is one of the most important public health concerns and its consequences represent a considerable social and health burden. The study analyses the occurrence of DM in Slovakia in 1992-2002. MATERIAL AND METHODS: Age standardised incidence and prevalence rates of DM were calculated from the data published by the Institute of Health Information and Statistics for 1992, 1997 and 2002. Disease length and the incidence of selected complications in 1997 and 2002 were also analysed. RESULTS: In 1992-2002, DM prevalence in Slovakia increased from 4261.3 to 5065.8 cases per 100,000 population and appeared to be positively associated with age, while the DM incidence rates rose from 329.6 to 423.7 cases per 100,000 population. In most patients, DM length was 5 years or less, showing an upward trend over the studied period. From 1997 to 2002, the rates of selected diabetic complications slightly increased (from 18.7 % to 20.3 % for peripheral neuropathy, from 16.8 % to 18.0 % for retinopathy, from 7.1 % to 8.0 % for nephropathy and from 1.2 % to 1.3 % for amputations). DISCUSSION AND CONCLUSIONS: Comparing with the world data, Slovakia ranks among the countries with relatively high prevalence of DM, mainly due to the rising incidence. These results are consistent with the global upward trend in DM. However, taking into account underreporting, the actual DM prevalence in Slovakia could be considerably higher. Besides primary prevention, risk reduction measures should be focused particularly on early diagnosis and better implementation of secondary prevention.

[HCV genotyping by combination of the Cobas Amplicor HCV 2.0 test and the reverse hybridization Versant HCV Genotype Assay]. / Vysetrení genotypu HCV pomocí kombinace testu Cobas Amplicor HCV 2.0 a reverzní hybridizace Versant HCV Genotype Assay.

Genotyping of hepatitis C virus (HCV) is of relevance to scheduling the treatment of patients with chronic hepatitis C (VHC), making their prognosis and monitoring the treatment efficacy. A set of 62 sera testing HCV RNA positive in Cobas Amplicor HCV 2.0 test (CA) were genotyped using Versant HCV Genotype Assay (LiPA) Bayer, i.e. the reverse hybridization method, with the CA amplified product being directly used in the assay. Fifty-six out of 57 samples reactive in reverse hybridization (92%) were genotyped. One sample showed a profile differing from any genotype, five samples were not reactive and one sample was not tested within this study design. Two out of five non-reactive sera and one non-tested serum could be genotyped by nested PCR based reverse hybridization. It can be concluded that the CA product resulting from one-step HCV RNA amplification is suitable for use in genotyping by reverse hybridization. The CA product based genotyping procedure is easier to perform, less time-consuming and less costly. The nested PCR based procedure could be used for typing of sera with lower HCV concentrations nontypeable with the combination of CA and Versant HCV Genotype Assay. Forty-eight selected samples were typed not only by reverse hybridization but also by a serological kit Murex HCV Serotyping 1-6 Assay (Abbot Murex). Thirty-seven (77%) of these sera, including all of three sera negative in reverse hybridization, appeared typeable by this kit. Although less sensitive, serotyping may be of relevance to typing of sera with low HCV levels or not containing detectable viral NA which are nontypeable by reverse hybridization. Thirty-three sera appeared genotypeable by both of the methods tested with the results being in good agreement. In two cases only the serotyping method revealed one more type of virus (mixed genotype) compared to the reverse hybridization.

Vaccinia virus recombinants co-expressing hepatitis B virus surface and core antigens.

Using the Praha strain of vaccinia virus (VV) two double recombinant VVs expressing the surface and capsid HBV proteins (HBsAg and HBcAg) under the control of the P7.5 promoter were constructed. In the first construct the gene coding for HBsAg was inserted into the HindIII J fragment (TK gene) and the gene coding for HBcAg was inserted into the HindIII M fragment (host range, K1L gene) of the VV genome. To test whether the expression of the foreign genes was influenced by the insertion site, in the second construct their locations were inversely changed. When compared with single VV-HBV recombinants expressing either HBsAg or HBcAg, the double recombinants expressed in vitro approximately the same amounts of the respective antigens. The particles formed by either HBsAg or HBcAg expressed by recombinant viruses, were isolated and examined by electron microscopy. Particles composed of both HBsAg and HBcAg were not detected in cultures infected with one of the double recombinants. The residual virulence in 3-week-old mice of the single recombinants was not markedly altered by the insertion of the second gene. The immunogenicity in mice of both the single and double recombinants was comparable and was not influenced by the location of the HBV genes in VV genome, as revealed by antibodies developed against the respective antigens.

Cardiovascular effects of diazepam and nitrazepam in combination with ethanol.

As little attention has been given to cardiovascular effects of a combination of benzodiazepines with ethanol up till now, this paper describes some studies of arterial blood pressure and heart rate in anaesthetized rats treated with diazepam or nitrazepam 5 mg X kg-1 and ethanol 2 g X kg-1. It was observed, that ethanol enhanced the mild hypotensive effect of both benzodiazepines and alone reduced arterial blood pressure in proportion to the rate of its absorption and actual plasma level. This effect may be supposed a synergistic effect caused by a changed biotransformation of benzodiazepines or by intensified central sedative action. The heart rate was not substantially influenced by this drug combination.