Vaspin: a novel adipokine, member of the family of serine protease inhibitors

In 2000, the novel adipokine vaspin, which belongs to the superfamily of serpins, was isolated from visceral adipose tissue. Vaspin is mainly produced in the visceral adipose tissue and is related to insulin resistance, blood glucose levels, sex hormones (women have higher levels compared to men) and nutritional status. Moreover, vaspin levels are modulated by weight loss and several agents, and it possibly constitutes a connecting link between obesity and its associated metabolic disorders. Many patients with polycystic ovary syndrome have insulin resistance, obesity (mostly visceral) and glucose intolerance, conditions associated with abnormalities in the production of vaspin. The role of vaspin in the regulation of human metabolism is unclear at present, but it appears that vaspin might represent a novel marker of obesity and insulin resistance. However, the controversial findings of existing studies on vaspin stress the need for further research in women with obesity and metabolic disorders in order to elucidate the role of this adipokine in these diseases and particularly in the polycystic ovary syndrome

Histology Verification Demonstrates That Biospectroscopy Analysis of Cervical Cytology Identifies Underlying Disease More Accurately than Conventional Screening:Removing the Confounder of Discordance

Background Subjective visual assessment of cervical cytology is flawed, and this can manifest itself by inter- and intra-observer variability resulting ultimately in the degree of discordance in the grading categorisation of samples in screening vs. representative histology. Biospectroscopy methods have been suggested as sensor-based tools that can deliver objective assessments of cytology. However, studies to date have been apparently flawed by a corresponding lack of diagnostic efficiency when samples have previously been classed using cytology screening. This raises the question as to whether categorisation of cervical cytology based on imperfect conventional screening reduces the diagnostic accuracy of biospectroscopy approaches; are these latter methods more accurate and diagnose underlying disease? The purpose of this study was to compare the objective accuracy of infrared (IR) spectroscopy of cervical cytology samples using conventional cytology vs. histology-based categorisation. Methods Within a typical clinical setting, a total of n = 322 liquid-based cytology samples were collected immediately before biopsy. Of these, it was possible to acquire subsequent histology for n = 154. Cytology samples were categorised according to conventional screening methods and subsequently interrogated employing attenuated total reflection Fourier-transform IR (ATR-FTIR) spectroscopy. IR spectra were pre-processed and analysed using linear discriminant analysis. Dunn?s test was applied to identify the differences in spectra. Within the diagnostic categories, histology allowed us to determine the comparative efficiency of conventional screening vs. biospectroscopy to correctly identify either true atypia or underlying disease. Results Conventional cytology-based screening results in poor sensitivity and specificity. IR spectra derived from cervical cytology do not appear to discriminate in a diagnostic fashion when categories were based on conventional screening. Scores plots of IR spectra exhibit marked crossover of spectral points between different cytological categories. Although, significant differences between spectral bands in different categories are noted, crossover samples point to the potential for poor specificity and hampers the development of biospectroscopy as a diagnostic tool. However, when histology-based categories are used to conduct analyses, the scores plot of IR spectra exhibit markedly better segregation. Conclusions Histology demonstrates that ATR-FTIR spectroscopy of liquid-based cytology identifies the presence of underlying atypia or disease missed in conventional cytology screening. This study points to an urgent need for a future biospectroscopy study where categories are based on such histology. It will allow for the validation of this approach as a screening tool

The Evaluation of p16ink4a Immunoexpression/Immunostaining and Human Papillomavirus DNA Test in Cervical Liquid-Based Cytological Samples

Aim: To evaluate the role of p16INK4a immunoexpression and human papillomavirus (HPV) DNA test for the detection of dyskaryotic cells in high-risk women. Materials and Methods: This work was a retrospective diagnostic study conducted in the University Hospital of Thessaloniki from January to December 2008. The subjects were women with current or previous HPV infection and current or previous cervical intraepithelial lesion (with or without treatment) or clinical warts. All liquid-based cytological samples were tested for P16INKa and HPV DNA test. The accuracy parameters used for the outcome included sensitivity, specificity, and positive predictive value. Results: A total of 226 women were included; the mean age was 29 years. Expression of p16INK4a was detected in the cytological samples of 13% of the negative cases, 44% of the cases of atypical squamous cells of undetermined significance, 46% of the cases of low-grade squamous intraepithelial lesion, and 78% of the cases of high-grade squamous intraepithelial lesion. A total of 91 women tested positive for high-risk HPV infection, and 54 of those had p16INK4a-positive staining reaction cells. The concordance between the 2 tests, HPV DNA and p16, was 59% regarding infection-positive cases. Diffuse strong parabasal p16INK4a immunostaining (nuclear score 92) was observed in 17 cases of the abnormal cytological findings (atypical squamous cells of undetermined significance, 2 cases; low-grade squamous intraepithelial lesion, 8 cases; high-grade squamous intraepithelial lesion, 7 cases). Colposcopy-directed biopsies were used as the criterion standard for the detection of cervical intraepithelial neoplasia in 91 women. The sensitivity of p16INK4a was 95% and the specificity was 92%, whereas the sensitivity of high-risk HPV was 100% and the specificity was 78%. The positive predictive value of p16INK4a was 71%, whereas that of HPV DNA was 44%. Conclusion: The findings suggest that p16INK4a immunostaining can improve the accuracy of cytological examination and HPV DNA test and may be particularly useful in the triage of low-grade lesions

Endometrial changes after methotrexate treatment: Relation with multiple nabothian cysts and future pregnancies

A clinical study was conducted in order to validate the effect of methotrexate on 30 patients with ectopic pregnancy (EP). A typical ultrasound appearance of multiple cysts of Naboth in the cervix was observed on six cases that are studied below. Endometrial sample with endogyn was retrieved from the six cases after the treatment with methotrexate was complete. The cytological results were studied and there were many changes found in the endometrial cells, in their cores, and some inflammatory cells as well. Two out of the six cases studied show more profound evidence. The cellular appearance of the endometrium after the treatment is discussed, in relation to the presence of multiple Nabothian cysts, as a result of inflammatory reaction, and the possibility of any influence in the capacity for a future pregnancy

Infrared (IR) spectral points of cytology in relation to normal histology.

<p>(<b>A</b>) IR spectra for normal histology classified according to the screening cytology results and in relation to the confidence ellipses of histology grades; and, (<b>B</b>) Analysis of IR spectra from normal cytology classified according to subsequent histology.</p

Correlation of cytology with subsequent histology.

<p>Correlation of cytology with subsequent histology.</p

Analysis of infrared (IR) spectra from cervical cytology samples with subsequent histology (<i>n</i> = 154). LD1 and LD2 were used to plot the confidence ellipses for cancer (violet), high-grade lesion (red), low-grade lesion (blue) and Negative (green).

<p>(<b>A</b>) Comparison of linear discriminant analysis (LDA) scores plots of IR spectra according to conventional cytology grades: Negative <i>vs.</i> LSIL <i>vs.</i> HSIL; (<b>B</b>) Comparison of LDA scores plots according to subsequent histology grades: Normal <i>vs.</i> CIN1 <i>vs.</i> CIN2+ <i>vs.</i> Cancer. In the next two figures, the scores plot for discordant cytology and histology were depicted by double-coloured symbols, with the outer colour determining the cytology grade and the inner colour determining the histology grade; (<b>C</b>) Comparison of LDA scores plots derived from IR spectra analysed using cytology-based categories; and, (<b>D</b>) Comparison of LDA scores plots derived from IR spectra analysed using subsequent histology-based categories.</p

Top six wavenumbers responsible for separating negative cytology from HPV, ASCUS and Cancer.

<p>Top six wavenumbers responsible for separating negative cytology from HPV, ASCUS and Cancer.</p

Infrared (IR) spectral points of cytology in relation to high-grade histology.

<p>(<b>A</b>) IR spectra for high-grade histology (CIN2+ and cancer) classified according to the screening cytology result and in relation to the confidence ellipses of histology grades; and, (<b>B</b>) Analysis of IR spectra of high-grade lesions cytology classified according to subsequent histology.</p