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.

Two Decades of Gla-100-Reflections from the Pivotal Clinical Trials.

The progressive nature of type 2 diabetes mellitus (T2DM) renders the shifting of patients from oral drugs to insulin therapy an inevitability in most patients especially in those with long duration of diabetes. At the turn of the last millennium, neutral protamine Hagedorn (NPH) insulin was still the only long-acting insulin available for people with diabetes. The advent of the first truly long-acting basal insulin, i.e. insulin glargine 100 U/mL (Gla-100) brought to the table a remarkably long duration of action and a very minimal risk of hypoglycemia by due to less pronounced peaks in their action profile. Further, in trying to achieve fasting normoglycemia, Gla-100 has demonstrated remarkably more holistic glucose-lowering efficacy in several pivotal trials compared to other insulin formulations, such as premixed insulin and coformulations-apart from NPH insulin. This article delineates clinical data on the effectiveness of Gla-100 vs. other insulin formulations in the context of T2DM.

Serum CCL 18 Levels in Women with Polycystic Ovarian Syndrome.

BACKGROUND: Polycystic ovarian syndrome (PCOS) is one of the most common metabolic disorders seen in women of the reproductive age group, with the majority of them having insulin resistance. There is a need to identify sensitive markers of insulin resistance. CC chemokine ligand 18 (CCL 18) secreted from white adipose tissue is upregulated in individuals with insulin resistance. OBJECTIVES: To study the correlation between serum CCL 18 levels and insulin resistance in PCOS. MATERIALS AND METHODS: This case-control study included 45 PCOS women and an equal number of age and body mass index (BMI) matched controls. Estimation of serum CCL 18, serum testosterone, fasting plasma glucose, fasting insulin, HbA1c, and ultrasonography of abdomen and pelvis was done and HOMA IR was calculated. RESULTS: Serum CCL 18 level was higher in women with PCOS when compared to controls. The mean level of serum CCL 18 (ng/mL) in the PCOS group and control group was 28.32 ± 4.17 and 11.90 ± 4.91, respectively (P < 0.001). Blood pressure, waist circumference, waist-hip ratio, modified Ferriman Gallway score (FG) score serum total testosterone, fasting serum insulin, and HOMA IR showed a relationship with serum CCL 18 levels. Serum CCL 18 was an independent predictor of PCOS (P < 0.05). A serum CCL 18 cutoff level of 18.84 ng/mL showed 93.3% sensitivity and 91.7% specificity in distinguishing PCOS subjects from healthy individuals. CONCLUSION: There is a significant correlation of serum CCL 18 level with insulin resistance in PCOS subjects and serum CCL levels can be considered as a marker of PCOS.

Serum Fibroblast Growth Factor 21 Levels in Patients with Hyperthyroidism and its Association with Body Fat Percentage.

BACKGROUND: Most of the actions of thyroid hormone (TH) on body metabolisms like maintenance of basal metabolic rate (BMR) and body fat are similar to that of fibroblast growth factor 21 (FGF21). We hypothesized that in patients with hyperthyroidism, the pathological changes in the BMR, body fat are mediated by TH through FGF21. OBJECTIVES: To study the association of serum FGF21 levels with hyperthyroidism and correlate body fat percentage with serum FGF21 levels in hyperthyroid patients. STUDY DESIGN: Case-control prospective follow-up study. METHODOLOGY: A total of 68 hyperthyroid patients and age, sex-matched healthy controls who fulfilled the inclusion and exclusion criteria were studied. Among them, 45 cases were followed up at 3 to 6 months after the achievement of euthyroidism. Body fat percentage was calculated from Jackson and Pollock 3 site equation and Siri equation. BMR percentage was calculated by the Gale formula. RESULTS: The mean age in years in the cases was similar to that of controls (36.14 ± 10.01 vs. 36.57 ± 10.53, P = 0.81). The serum FGF21 levels at baseline were significantly elevated in patients with hyperthyroidism compared to controls [median 406.6 pg/ml (interquartile range, 262.9-655.6) vs. 252.3 (125.1-341) P < 0.001] and declined dramatically following treatment with anti-thyroid drugs [405 (275.5-680.4) vs. 203.6 (154.6-230.6) P < 0.001]. Serum FGF21 levels negatively correlated with body fat percentage (r = -0.268, P = 0.002). After adjusting to various confounding factors, serum FGF21 was independently associated with hyperthyroidism and was significant. (OR [95%CI] 3.78 (1.046-13.666) P = 0.043). CONCLUSION: Serum FGF21 levels were elevated in hyperthyroid patients and decreased following treatment with anti-thyroid drugs. It was independently associated with hyperthyroidism. There may be a future therapeutic role of FGF21 inhibition in the reversal of these changes in addition to anti-thyroid drugs in patients with hyperthyroidism.

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.

Serum adiponectin levels in gestational diabetes mellitus.

INTRODUCTION: Gestational diabetes mellitus (GDM) is defined as any degree of glucose intolerance with onset or first recognition during pregnancy.[1] Pregnancy is a unique situation in which there is a physiological temporary increase in insulin resistance (IR). The mechanisms responsible for the gestational-induced IR are not completely understood. The current study was undertaken to compare adiponectin levels during 24-28 weeks period of gestation in drug-naive newly diagnosed GDM women with a cohort of normoglycemic pregnant women. SUBJECTS AND METHODS: A total of 47 pregnant women in the age group of 18-40 years were included in this cross-sectional study, of which 13 were GDM cases and 34 were normoglycemic controls. Serum adiponectin level was analyzed by enzyme-linked immunosorbent assay. RESULTS: The mean adiponectin level was 16.92 ng/ml (standard deviation [SD] = 2.78) and 19.38 ng/ml (SD = 2.71) in case and control groups, respectively, and the difference was found to be statistically significant (P = 0.008). CONCLUSION: Our study demonstrated decreased serum adiponectin levels in women with GDM when compared with age- and body mass index-matched euglycemic pregnant women.

Adult hypopituitarism: Are we missing or is it clinical lethargy?

Hypopituitarism, a disease of varied etiologies, is a serious endocrine illness that requires early recognition and prompt treatment to avoid its severe deleterious effects. In adults it is often missed due to non-specific symptoms of growth hormone deficiency and hypogonadism or mild deficiencies of other pituitary hormones. In some it may present with acute onset of symptoms suggestive of acute adrenal (corticotropin) insufficiency or symptoms due to mass lesion in/or around pituitary. High index of suspicion is required to seek hypopituitarism in patients with non-specific symptoms such as fatigue and malaise. Treatment of isolated hormone deficiency, partial or panhypopituitarism, has gratifying results although they require lifelong treatment and follow-up.

Geo - hydrological investigations and impact of water harvesting structures on groundwater potential in Anantapur District, Andhra Pradesh, India.

In this paper, the data pertaining to the rainfall, its departure from normal, moving mean rainfall, depth of water levels in pre-monsoon and post-monsoon seasons, groundwater availability, groundwater utilization and impact of storage of water in large water bodies are analyzed graphically. The results indicate that the groundwater is over exploited in many places in Anantapur District (India). The groundwater levels found fluctuating, when compared the observations in pre-monsoon and post-monsoon seasons. Hence, it is concluded that the construction of water harvesting structures at suitable locations will have a definite impact on the groundwater potential in Anantapur District.

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.

Partial activation and induction of apoptosis in CD4(+) and CD8(+) T lymphocytes by conformationally authentic noninfectious human immunodeficiency virus type 1.

Increased levels of apoptosis are seen in human immunodeficiency virus (HIV) infection, and this has been proposed as an important mechanism contributing to HIV pathogenesis. However, interpretation of in vitro studies aimed at understanding HIV-related apoptosis has been complicated by the use of high concentrations of recombinant proteins or by direct cytopathic effects of replicating virus. We have developed an inactivation procedure that destroys retroviral infectivity while preserving the structural and functional integrity of the HIV surface proteins. These noninfectious virions interact authentically with target cells, providing a powerful tool to dissect mechanisms of HIV pathogenesis that do or do not require viral replication. Noninfectious CXCR4-tropic HIV-1 virions, but not microvesicles, partially activated freshly isolated CD4(+) and CD8(+) peripheral blood mononuclear cell T lymphocytes to express FasL and Fas, but not CD69 or CD25 (interleukin-2 receptor alpha) and eventually die via apoptosis starting 4 to 6 days postexposure. These effects required conformationally intact virions, as heat-denatured virions or equivalent amounts of recombinant gp120 did not induce apoptosis. The maximal apoptotic effect was dependent on major histocompatibility complex (MHC) class II proteins being present on the virion, but was not MHC restricted. The results suggest that the immunopathogenesis of HIV infection may not depend solely on direct cytopathic effects of HIV replication, but that effects due to noninfectious HIV-1 virions may also contribute importantly.

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.

High viral load in the cerebrospinal fluid and brain correlates with severity of simian immunodeficiency virus encephalitis.

AIDS dementia and encephalitis are complications of AIDS occurring most frequently in patients who are immunosuppressed. The simian immunodeficiency virus (SIV) model used in this study was designed to reproducibly induce AIDS in macaques in order to examine the effects of a neurovirulent virus in this context. Pigtailed macaques (Macaca nemestrina) were coinoculated with an immunosuppressive virus (SIV/DeltaB670) and a neurovirulent molecularly cloned virus (SIV/17E-Fr), and more than 90% of the animals developed moderate to severe encephalitis within 6 months of inoculation. Viral load in plasma and cerebrospinal fluid (CSF) was examined longitudinally to onset of AIDS, and viral load was measured in brain tissue at necropsy to examine the relationship of systemic and central nervous system (CNS) viral replication to the development of encephalitis. In all animals, plasma viral load peaked at 10 to 14 days postinfection and remained high throughout infection with no correlation found between plasma viremia and SIV encephalitis. In contrast, persistent high levels of CSF viral RNA after the acute phase of infection correlated with the development of encephalitis. Although high levels of viral RNA were found in the CSF of all macaques (six of six) during the acute phase, this high level was maintained only in macaques developing SIV encephalitis (five of six). Furthermore, the level of both viral RNA and antigen in the brain correlated with the severity of the CNS lesions. The single animal in this group that did not have CNS lesions had no detectable viral RNA in any of the regions of the brain. The results substantiate the use of CSF viral load measurements in the postacute phase of SIV infection as a marker for encephalitis and CNS viral replication.

Nef enhances human immunodeficiency virus replication and responsiveness to interleukin-2 in human lymphoid tissue ex vivo.

The nef gene is important for the pathogenicity associated with simian immunodeficiency virus infection in rhesus monkeys and with human immunodeficiency virus type 1 (HIV-1) infection in humans. The mechanisms by which nef contributes to pathogenesis in vivo remain unclear. We investigated the contribution of nef to HIV-1 replication in human lymphoid tissue ex vivo by studying infection with parental HIV-1 strain NL4-3 and with a nef mutant (DeltanefNL4-3). In human tonsillar histocultures, NL4-3 replicated to higher levels than DeltanefNL4-3 did. Increased virus production with NL4-3 infection was associated with increased numbers of productively infected cells and greater loss of CD4(+) T cells over time. While the numbers of productively infected T cells were increased in the presence of nef, the levels of viral expression and production per infected T cell were similar whether the nef gene was present or not. Exogenous interleukin-2 (IL-2) increased HIV-1 production in NL4-3-infected tissue in a dose-dependent manner. In contrast, DeltanefNL4-3 production was enhanced only marginally by IL-2. Thus, Nef can facilitate HIV-1 replication in human lymphoid tissue ex vivo by increasing the numbers of productively infected cells and by increasing the responsiveness to IL-2 stimulation.