PET-CT scan-based maximum standardized uptake value as a prognostic predictor in oropharynx squamous cell cancer.

INTRODUCTION: Positron emission tomography with 2-deoxy-2-[fluorine-18]fluoro-D-glucose integrated with computed tomography (18F-FDG PET-CT) is clinically useful and extensively used in initial staging and follow-up of patients with head and neck squamous cell carcinoma (HNSCC). We studied the potential prognostic significance of primary tumor maximum standard uptake value (SUVmax) by 18F-FDG PET-CT in oropharyngeal cancer. METHODS: Sixty patients with early and locally advanced histopathologically proven oropharyngeal squamous cell cancer were staged using FDG PET-CT at diagnosis. All patient received radiation therapy and concurrent chemotherapy (in stage III and IVA disease) and were assessed prospectively for treatment outcome. Groups were created based on stage and cut off for SUVmax. The association of SUVmax of primary tumour and stage with disease-free survival and overall survival was analyzed by univariate and multivariate statistics. RESULTS: In univariate analysis, a primary tumour SUVmax of greater than 13.0 and advanced stage (IVA) predicted inferior disease-free survival (P=0.0241 and 0.0005, respectively) and overall survival (P=0.0510, toward significance and 0.0003, respectively). In proportional hazards analysis, stage was significant only when adjusted for primary SUVmax. CONCLUSION: SUVmax failed to demonstrate predictive significance in oropharyngeal cancer, and an increase in primary tumor uptake is possibly a direct effect of advanced disease and consequently increased metabolic activity and aggressiveness.

46 XX, SRY Negative Ovotesticular DSD.

46 XX ovotesticular DSD is a rare disorder. It presents with cryptorchidism, hypospadias or ambiguous genitalia at birth, gynaecomastia in adolescent stage or infertility in adult age. We report here a 20 year old phenotypically male who presented with gynaecomastia and found to have testis on right side and left inguinoscrotal swelling consisting of ovary, uterus and fallopian tubes. Evaluation revealed SRY negative 46 XX karyotype. He underwent surgical removal of ovary and mullerian structures. The highlight of case is development of testicular tissue in absence of SRY gene.

Comparison of follitropin-beta administered by a pen device with conventional syringe in an ART programme - a retrospective study.

OBJECTIVES: This study compares the efficacy and patient tolerance of follitropin-beta (recagon) administered using a pen device with conventional syringe in infertile couples undergoing in vitro fertilization/intracytoplasmic sperm injection treatment. METHODS: Data for 481 patients were retrieved retrospectively for the analysis. Conventional syringe group constituted 204 patients with 217 cycles and 265 patients with 294 cycles in the pen-device group. Down-regulation was achieved with GnRH agonist. RESULTS: Comparison of follitropin-beta administered with pen and syringe showed the following data, respectively. A total dose of 1909.38/2100.65 IU (P < 0.001), duration of stimulation, 9.70/10.47 days (P < 0.05), oestradiol levels on the day of human chorionic gonadotropin, 1488.34/1067.63 pg/ml, number of follicles reaching >16-mm size, 9.75/7.34 (P < 0.05), number of oocytes retrieved, 13.84/9.55 (P < 0.001) and number of embryos available for freezing, 4.56/1.30 (P < 0.05), the above data were observed in pen/conventional syringe groups, respectively. The live birth rates per cycle were 28.85% and 30.95% in the conventional syringe/pen-device groups, respectively. Patient tolerance with respect to pain at injection site was better with the pen device (P < 0.025). CONCLUSION: The data show that follitropin-beta administered with pen device is well tolerated and more efficacious with respect to ovarian stimulation outcome compared with the conventional syringe.

Parathyroid Neoplasms: The Army Hospital (Research & Referral) Experience.

BACKGROUND: Neoplasms of the parathyroid are common but parathyroid carcinoma is exceptionally rare. In contrast to most other malignant endocrine tumours that are usually less hormonally active, malignant parathyroid tumours are hyper functional. Malignant parathyroid tumours pose a diagnostic dilemma for the pathologist. OBJECTIVE: To study the clinicopathological profile of a case series of parathyroid neoplasms and determine features which facilitate a malignant diagnosis. METHODS: A retrospective analysis of seven cases of surgically treated parathyroid tumours over a three-year period at a single centre was done. Clinical, haematological, biochemical, and radiological data was accrued from medical records. The histopathology slides were reviewed along with the clinicopathological profile in an attempt to delineate markers of malignancy. RESULTS: Patients ranged from 30 to 58 years of age. Males and females were approximately equal. Weakness and bone pain were the commonest presenting symptoms. Over 50% had significant hypercalcaemia and all had elevated serum parathormone. Clinically apparent mass was seen in only one. All tumours were successfully localised using CT scan and MRI. Thick fibrous capsule and broad septal fibrosis was seen in both the carcinomas; these were thin in the adenomas. Mitotic counts of 1-3 per high power field (HPF), capsular invasion and nodal metastasis were noted in the malignant tumours. CONCLUSION: Elevated serum calcium and parathormone values point to a parathyroid neoplasm. Current imaging modalities are successful in localising the tumour preoperatively. Markedly elevated serum calcium, broad fibrous bands, mitotic counts and capsular invasion are indicators of malignancy.

The central nervous system as a reservoir for simian immunodeficiency virus (SIV): steady-state levels of SIV DNA in brain from acute through asymptomatic infection.

Latent reservoirs of human immunodeficiency virus (HIV) present significant challenges for eradicating HIV from infected persons, particularly reservoirs in the brain established during acute infection. A simian immunodeficiency virus (SIV)/macaque model of HIV dementia was used to show that viral DNA levels in the brain remained at constant levels from acute through asymptomatic infection, despite significant down-regulation of viral RNA in the brain after the acute phase of infection. Viral replication in the brain coincided with activation of macrophages and microglia in the central nervous system; down-regulation of viral replication coincided with increased infiltration of cytotoxic lymphocytes and reduced activation of macrophages and microglia in the brain. Comparison of viral genotypes in the central nervous system and peripheral blood mononuclear cells suggests that recrudescence of viral replication in brain occurs by reactivation of latent viral DNA. Latent virus in the brain must be considered in therapeutic strategies to eliminate HIV from infected persons.

Real-time polymerase chain reaction assay for cell-associated HTLV type I DNA viral load.

We have developed a quantitative real-time PCR assay for HTLV-I DNA. This assay approach uses real-time monitoring of fluorescent signal generation as a consequence of Taq-mediated amplification of specific target sequences to allow real-time kinetic analysis of amplicon production. This kinetic approach yields excellent sensitivity and an extremely broad linear dynamic range, and ensures that quantitation is based on analysis during the exponential phase of amplification, regardless of the input template copy number. The HTLV-I DNA assay has a nominal threshold sensitivity of 10 copy Eq/reaction, although single-copy plasmid template can be detected at frequencies consistent with statistical prediction. The linear dynamic range is in excess of 5 logs. Interassay reproducibility averages 14% (coefficient of variation) for control templates over a range of 10(1) to 10(6) copy Eq/reaction and 25%, based on studies of extraction and analysis of replicate aliquots of PBMC specimens from HTLV-I-infected subjects. The primer/probe combination targets tax sequences conserved across described HTLV-I and HTLV-II isolates. Parallel quantitation in the same samples of an endogenous sequence present at a known copy number per cell allows normalization of results for potential variation in DNA recovery. Availability of this assay should facilitate studies of basic pathogenesis and clinical evaluation of HTLV-I and HTLV-II infection, as well as assessment of therapeutic approaches.

Parapharyngeal space mesenchymal chondrosarcoma in childhood.

A case of extra osseous mesenchymal chondrosarcoma occuring in the parapharyngeal space in a 7-year-old girl, is being presented for its rarity. It is a slow growing, locally aggressive tumour with a high incidence of local recurrence as well as distant metastasis. It is rare in the pediatric age group and rarer in the parapharyngeal space. It has a poor prognosis, the 5-year survival rate varies between 30 and 50%. Radical surgery is the treatment of choice. Radiotherapy and chemotherapy have an adjuvant role. More experience with this tumour is required to evaluate the most effective treatment. Current literature on this subject has been reviewed.

Inactivation of human immunodeficiency virus type 1 infectivity with preservation of conformational and functional integrity of virion surface proteins.

Whole inactivated viral particles have been successfully used as vaccines for some viruses, but procedures historically used for inactivation can denature virion proteins. Results have been inconsistent, with enhancement of disease rather than protection seen in some notable instances following vaccination. We used the compound 2,2'-dithiodipyridine (aldrithiol-2; AT-2) to covalently modify the essential zinc fingers in the nucleocapsid (NC) protein of human immunodeficiency virus type 1 (HIV-1) or simian immunodeficiency virus (SIV) virions, thereby inactivating infectivity. The inactivated virus was not detectably infectious in vitro (up to 5 log units of inactivation). However, in contrast to virions inactivated by conventional methods such as heat or formalin treatment, viral and host cell-derived proteins on virion surfaces retained conformational and functional integrity. Thus, immunoprecipitation of AT-2-treated virions was comparable to precipitation of matched untreated virus, even when using antibodies to conformational determinants on gp120. AT-2 inactivated virions bound to CD4(+) target cells and mediated virus-induced, CD4-dependent "fusion from without" comparably to native virions. However, viral entry assays demonstrated that the viral life cycle of AT-2-treated virions was arrested before initiation of reverse transcription. The major histocompatibility complex (MHC) class II molecules on the surface of AT-2-treated virions produced from MHC class II-expressing cells retained the ability to support class II-dependent, superantigen-triggered proliferative responses by resting T lymphocytes. These findings indicate that inactivation via this method results in elimination of infectivity with preservation of conformational and functional integrity of virion surface proteins, including both virally encoded determinants and proteins derived from the host cells in which the virus was produced. Such inactivated virions should provide a promising candidate vaccine antigen and a useful reagent for experimentally probing the postulated involvement of virion surface proteins in indirect mechanisms of HIV-1 pathogenesis.

Glomus jugulare.

Glomus Jugulare tumours are relatively rare. In the early stages the symptoms may simulate other otological conditions such as acute otitis media. We report a case of a 34 year old male with Glomus Jugulare, where the diagnosis was initially missed and later made on development of classical symptoms. The management of this case and a brief review of literature is presented. The aim is to highlight the importance of early diagnosis and successful outcome following surgery.

Replication of measles virus in human monocytes and T cells.

Replication of measles virus (MV) in populations of peripheral blood mononuclear cells enriched for T cells and monocytes was studied using a temperature-sensitive mutant, MV ts38, and the parent counterpart, MV Lec. Stimulation of the cells was required for a full cycle of virus replication in both cell types. More infectious virus was released after stimulation from MV-infected populations enriched for T cells, T cell-enriched than from monocyte-enriched populations. However, similar amounts of viral mRNA, genomic RNA, and viral proteins of the expected size were found in both cell populations. The results indicate that MV-specific macromolecular synthesis is similar in both T cells and monocytes, but the assembly and (or) release of infectious virus is greatly reduced in monocytes as compared with T cells.