Cytologic features of central giant-cell granuloma of the jaw

In this present series, we studied in detail the cytologic features of five histopathologically verified cases of central giant-cell granuloma (CGCG). All the patients in this series were female, with an age range of 11-60 years. There were three cases with involvement of the lower jaw and two cases had upper jaw involvement. Cytology smears showed dispersed single cells in the background. Nuclei of the individual cells were round to ovoid with fine chromatin and inconspicuous nucleoli. The cytoplasm of these cells was moderate in amount with indistinct cell borders. Many randomly scattered multinucleated giant cells with 10-20 nuclei were present in the background. Combination of clinical features, radiologic pictures, and cytologic features may be helpful for diagnosis of CGCG on fine-needle aspiration cytology.     

Bacterial clearance of Pseudomonas aeruginosa is enhanced by the inhibition of COX-2

Prostanoids generated by COX-2 are involved in the regulation of inflammation but their exact role in the innate immune response has not been defined. We investigated whether COX-2 is involved in host defense against Pseudomonas aeruginosa pneumonia. In vitro studies, in a macrophage cell line, showed that cytotoxic strain of P aeruginosa (PA103) induced significant COX-2 protein expression and enzymatic function. In vivo data showed that infection with PA103 increased COX-2 protein production in whole lung tissue compared to mice that were infected with mutant bacteria that lack ExoU (DeltaU) or ExoU and ExoT (DeltaUT). COX-2(-/-) mice had accentuated clearance of cytotoxic P. aeruginosa from the lungs. We further tested the effects of COX-2 products such as prostaglandin E(2) on the function of phagocytic cells. Our studies indicate that prostaglandin E(2) may be involved through interacting with the EP2 receptors in modulating the host response because treatment of macrophages with prostaglandin E(2) suppressed production of reactive oxygen species. Furthermore there was enhanced bacterial clearance in EP2 receptor(-/-) mice compared to the wild-type controls. Thus it is possible that inhibition of COX-2 or EP2 receptors could be an effective adjunctive treatment for severe or resistant P. aeruginosa pneumonia.     

Leishmania donovani-induced ceramide as the key mediator of Akt dephosphorylation in murine macrophages: role of protein kinase Czeta and phosphatase

Leishmania donovani is an intracellular protozoan parasite that impairs the host macrophage immune response to render it suitable for its survival and establishment. L. donovani-induced immunosuppression and alteration of host cell signaling is mediated by ceramide, a pleiotropic second messenger playing an important role in regulation of several kinases, including mitogen-activated protein kinase and phosphatases. We observed that the endogenous ceramide generated during leishmanial infection led to the dephosphorylation of protein kinase B (PKB) (Akt) in infected cells. The study of ceramide-mediated Akt phosphorylation revealed that Akt was dephosphorylated at both Thr308 and Ser473 sites in infected cells. Further investigation demonstrated that ceramide was also responsible for the induction of PKCzeta, an atypical Ca-independent stress kinase, as well as the ceramide-activated protein phosphatases (e.g., protein phosphatase 2A [PP2A]). We found that Akt dephosphorylation was mediated by ceramide-induced PKCzeta-Akt association and PP2A activation. In addition, treatment of L. donovani-infected macrophages with PKCzeta-specific inhibitor peptide could restore the translocation of phosphorylated Akt to the cell membrane. This study also revealed that ceramide is involved in the inhibition of proinflammatory cytokine tumor necrosis factor alpha release by infected macrophages. These observations strongly suggest the importance of ceramide in the alteration of normal cellular functions, impairment of the kinase/phosphatase balance, and thereby establishment of leishmaniasis in the hostile macrophage environment.     

The long-term effectiveness of generic adult fixed-dose combination antiretroviral therapy for HIV-infected Ugandan children

Background

Access to pediatric antiretroviral formulations is increasing in resource-limited countries, however adult FDCs are still commonly used by antiretroviral therapy (ART) programs.

Objective

To describe long-term effectiveness of using adult FDC of d4T+3TC+NVP (Triomune) in children for HIV treatment.

Methods

Clinical, immunologic, and virologic outcomes of HIV-infected ART-naïve children aged six months to 12 years, were evaluated up to 96 weeks post-ART initiation.

Results

From March 2004 to June 2006, 104 children were followed with a median age of 5.4 years, median CD4 cell percent and HIV-1 RNA were 11.0% (IQR 6.7–13.9) and 348,846copies/mL (IQR 160,941–681,313) respectively at baseline. Using Kaplan-Meir estimates, 75% of children had undetectable viral loads (<400copies/mL) at 96weeks of ART. Children with a baseline CD4 cell percent >15% were 3 times more likely to achieve viral load <400copies/mL than those with baseline CD4 cell percent <5% after adjusting for baseline age {aHR = 3.03 (1.10–8.32), p=0.03}; no difference was found among those with CD4 cell percent >5–14.9% and <5%.

Conclusion

Treatment with generic adult FDC for HIV-infected Ugandan children led to sustained clinical, immunologic and virologic response during 96 weeks of ART. Early initiation of ART is key to achieving virological success.     

Fine-needle aspiration in the evaluation of thyroid lesions in children

The role of fine-needle aspiration (FNA) cytology in the evaluation of thyroid lesions in not as well established in children when compared with adults. Hence we aimed to ascertain the utility and limitations of FNA in childhood thyroid lesions. This was a retrospective analysis of all thyroid FNA performed in children less than 14 years of age over a 4-year period (2005-2009). Histopathological follow-up was available in six cases. A total of 77 cases were included in the analysis. The most common cytological diagnosis was lymphocytic thyroiditis (49.3%), followed by colloid goiter (18.2%), hyperplasia (10.4%), and benign aspirate (7.8%); malignancy was identified in six cases (7.8%). Of these six cases, three were papillary thyroid carcinoma. There was one false-positive case reported as a Hurthle-cell neoplasm, which on histology showed Hashimoto's thyroiditis. One case each of rhabdomyosarcoma and spindle epithelial tumor with thymus like differentiation was wrongly diagnosed as thyroid neoplasm, NOS, and medullary carcinoma (spindle variant), respectively. The overall diagnostic accuracy was 98.6% with 100% sensitivity, 98.6% specificity, 80% positive predictive value, and 100% negative predictive value. FNA is extremely valuable in the initial evaluation of thyroid swelling in children. Rare neoplasms masquerading as thyroid nodules in children can pose difficulties in diagnosis; however, papillary carcinoma is easily recognized. In lymphocytic thyroiditis, it provides a tissue diagnosis, thereby avoiding more invasive procedure for merely diagnostic purposes.     

Role of DNA flow cytometry and image cytometry on effusion fluid

The objective of the study was to assess the value of DNA flow cytometry (FCM) and image cytometry (ICM) as an adjunct to routine diagnostic cytology. In this prospective study, 100 consecutive effusion fluids were studied for routine cytology, DNA FCM, and in selected cases, ICM. One half of the centrifuged fluid sample was used for routine cytology and the remaining portion was used for DNA FCM. Nuclear area, nuclear diameter, nuclear perimeter, nuclear convex perimeter, nuclear roundess, and nuclear convex area were measured on at least 100 cells by ICM in cytologically malignant or DNA aneuploid cases along with control cases. Clinical follow-up was done in all cases. There were 22 cytologically malignant cases and 78 cytologically benign cases. Among the 22 cytologically malignant cases, there were 11 aneuploid and diploid cases each by DNA FCM. Out of 78 cytologically benign cases, six (7.7%) were aneuploid by DNA FCM. Smears of these cases showed predominantly reactive mesothelial cells, but the DNA histograms showed hypodiploid (one), hyperdiploid (three), tetraploid (one), and hypertetraploid (one) aneuploidy. Follow-up of these cases showed clinical or histologic features of malignancy except in one case of tetraploid aneuploidy, which did not show any features of malignancy and responded well to antitubercular therapy. Therefore, out of 27 malignant effusions, DNA FCM picked up 16 cases and routine cytology detected 22 cases. Sensitivity and specificity of DNA FCM were thus 59.25% and 98.63%, respectively. There was a statistically significant difference (Student's unpaired t-test, P < 0.05) between cytologically malignant cases and control benign cases in all the nuclear morphometric parameters except for nuclear roundness. There was, however, no statistically significant difference of nuclear morphometric parameters between cytologically benign vs. DNA aneuploid cases and control benign cases. DNA FCM is a useful adjunct for routine diagnostic cytology. Visual diagnostic cytology and morphometric digital microscopy miss some cases of malignancy which can be detected by DNA flow cytometry. Diagn. Cytopathol. 2000;22:81-85.     

Correlations between apoptotic and proliferative indices in cervical intraepithelial neoplasia and carcinoma

Aims of the present paper was to study cell death by apoptosis and cell proliferation in normal cervical biopsies, cervical intraepithelial neoplasms (CIN) and squamous cell carcinomas of cervix (CaCx). There were each seven cases of normal cervical biopsy, CIN1 and CIN2 along with 10 cases of CIN3 and 14 cases of CaCx. Percentage of apoptotic cells and bodies (i.e. apoptotic index, AI) and mitoses (i.e. mitotic index, MI) and turnover index (TI - AI + MI) were counted in formalin fixed, paraffin embedded, haematoxylin and eosin stained slides. AgNOR stain was done and mean AgNOR dots per cell was also estimated. AI, MI and TI were correlated with histology grade of CIN and invasive carcinoma cervix. Mean AI, MI, TI and AgNOR count increased from lower to higher grades of CIN. AI, MI & TI raised significantly from CIN3 to carcinomas; AI, TI & AgNOR count raised significantly from CIN1 to combined CIM2 & 3; TI & AgNOR count were high in CIN1 to CIN2; AI & TI were significantly raised in normal to CIN1. In conclusion, TI is probably more important for cell kinetic analysis of CIN and carcinoma of cervix because it reflects the frequency of two important events i.e. mitosis and cell death. Sudden increase of AI, MI, TI count from CIN3 to CaCx may indicate the possibility of genetic alteration of cells of CIN3 which induces a frank malignant transformation from CIN3 to CaCx.