Citrullinemia, a rare cause of recurring encephalopathy.

An infant presented with recurrent episodes of encephalopathy, responding to nonspecific management of sepsis. High index of suspicion helped uncover underlying error of metabolism.

A Case of Mixed Gonadal Dysgensis: A Diagnostic Challenge.

A 2-year-old child reared as a girl child was brought by parents with ambiguous genitalia noticed since birth. There was no history of failure to thrive or salt-losing crisis. On examination, the child had normal height and weight with normal blood pressure and no dysmorphism or Turners stigmata with external genitalia Prader Score 2. Ultrasound of the pelvis revealed hypoplastic uterus with no gonads visualized. There was no evidence of hypocortisolemia (8 am cortisol 14.08 mcg/dl) or elevated level of 17-OH-progesterone (1.1 ng/mL). Pooled follicle-stimulating hormone and luteinizing hormone levels were 2.66 mIU/ml and 0.1 mIU/ml, respectively, thyroid-stimulating hormone: 2.36 mIU/L, T4: 134.5 nmol/L, total testosterone: 2.5 ng/dl. Posthuman chorionic gonadotropin stimulation showed total testosterone levels 267 ng/dL, dihydrotestosterone: 155 pg/mL, androstenedione: 0.3 ng/mL indicating functioning testicular tissue without any evidence of 17-beta hydroxylase or 5-alpha reductase deficiency. Karyotyping revealed 45, XO genotype on two separate occasions. In view of the discrepancy between karyotype finding and ultrasound reports with the clinical and hormonal picture, fluorescence in situ hybridization cytogenetic study was carried out and showed MONOSOMY X (90% cells)/SEX ANEUPLOIDY XYY (10% cells). Laparoscopic examination showed gonad in the right ovarian fossa and left streak gonad with bilateral fallopian tubes and hypoplastic uterus. Genitoscopy showed normal vagina and cervix. Cystoscopy showed normal urethra and urinary bladder. Biopsy was taken from both gonads. A thorough histopathological examination of this specimen showed the structure of seminiferous tubules with Leydig cells in the right gonad with streak ovary on the left side. The child underwent bilateral gonadectomy and rehabilitated her to lead a life as a girl.

Collaborating to Compete: Blood Profiling Atlas in Cancer (BloodPAC) Consortium.

The cancer community understands the value of blood profiling measurements in assessing and monitoring cancer. We describe an effort among academic, government, biotechnology, diagnostic, and pharmaceutical companies called the Blood Profiling Atlas in Cancer (BloodPAC) Project. BloodPAC will aggregate, make freely available, and harmonize for further analyses, raw datasets, relevant associated clinical data (e.g., clinical diagnosis, treatment history, and outcomes), and sample preparation and handling protocols to accelerate the development of blood profiling assays.

Steroid and metabolic hormonal profile of porcine serum vis-à-vis ovarian follicular fluid.

AIM: This study was conducted to understand whether serum level of the steroid and metabolic hormones may be indicative of their level in ovarian follicular fluid (FF) in porcine, and its influence on fertility. MATERIALS AND METHODS: Ovaries from pigs (n=32) of two genetic groups, namely, native (Ghungroo; n=16) and crossbred (Hampshire × Ghungroo; n=16) were collected. Both the genetic groups comprised gilts (n=8) and sows (n=8), and sows were in luteal phase of estrus cycle. FF was aspirated from small, medium and large follicles, and centrifuged for the collection of supernatant for further analysis. Blood samples were collected from the same animals, and serum was separated. Hormones, namely, cortisol, T3, T4 and testosterone were estimated by radioimmunoassay. Two-way ANOVA was used for analysis of data considering genetic background (native or crossbred), stage of reproductive life (gilt or sow), and source of sample (serum or FF) as fixed effects. RESULTS: It was observed that all the hormones except cortisol differed significantly (p<0.01) based on genetic background. Stage of reproductive life and source of sample did not affect the studied hormonal level. Within the genetic groups, stage of reproductive life influenced T3 (p<0.01), cortisol (p<0.05) and testosterone (p<0.01) level in crossbred pigs as compared to T3 (p<0.01) only in native pigs. The level of T3 in serum, as well as FF, was higher (p<0.01) in Ghungroo gilts compared to sows. However, a reverse of this was observed in the case of crossbred pigs. The level of cortisol (p<0.05) and testosterone (p<0.01) was higher in crossbred sows than gilts in both serum and FF. CONCLUSION: The study revealed that serum level of the steroid and metabolic hormones is indicative of their level in the ovarian FF. Further, varying level of steroid and metabolic hormones in pigs based on genetic background may be due to variation in body size, rate of energy metabolism and stage of (re)productive life.

Effect of holding of semen and washing of seminal plasma on quality and fertility of Hampshire boar semen preserved at liquid state.

The present study was aimed to reveal the effect on keeping quality of boar semen on holding or not holding at an elevated temperature than that used for preservation when combined with washing or not washing of seminal plasma. Twenty ejaculates, four from each of five Hampshire boars were used to hold for 0 and 4h in GEPS extender at 22°C and subsequently washed (1500×g for 10min) of seminal plasma or left unwashed and preserved at 15°C for 72h after extending with the same extender. The seminal parameters in terms of sperm motility, live spermatozoa, and live spermatozoa with intact acrosome (LIA) were evaluated at 0h-(immediately after extension) and thereafter at 24h intervals. The mean percentage of sperm motility was significantly (P<0.01) higher in unwashed than washed semen at both 0h and 4h of holding irrespective of preservation period. It was significantly (P<0.01) higher in semen held for 4h than 0h irrespective of washing and significantly (P<0.01) lower in washed than in unwashed semen irrespective of holding during preservation. Irrespective of preservation period the mean percentage of live spermatozoa was significantly (P<0.01) higher with 4h than 0h of holding in both unwashed and washed semen and was significantly (P<0.01) higher in unwashed than washed semen at both 0h and 4h of holding. It was significantly (P<0.01) higher for 4h held semen irrespective of washing and was significantly (P<0.01) lower in washed than in unwashed semen irrespective of holding during preservation. The mean percentage of LIA was significantly (P<0.01) higher with 4h than with 0h holding in both unwashed and washed semen and was significantly (P<0.01) higher in unwashed than in washed semen at both 0h and 4h of holding irrespective of preservation period. It was significantly (P<0.01) higher for 4h held as compared to unheld semen irrespective of washing and was significantly (P<0.01) lower in washed than unwashed semen irrespective of holding during preservation. The mean percentage of sperm motility, live spermatozoa and LIA decreased significantly (P<0.01) in 0h and 4h holding irrespective of washing and in unwashed and washed semen irrespective of holding with increase in preservation period. Among all the treatments unwashed semen held for 4h yielded superior sperm quality on preservation. A total of 32 female pigs were inseminated using preserved semen obtained with the best processing technique found in the study. The conception rate, farrowing rate and litter size at birth were recorded to be 81.25%, 78.13% and 7.96 respectively as compared to 73.38%, 67.57% and 6.68 respectively in the control group. It could be concluded that unwashed Hampshire boar semen held for 4h, extended with GEPS and preserved at 15°C for 72h was conducive to obtain optimum fertility and fecundity in females when used for artificial insemination.

Identification of site-specific prognostic biomarkers in patients with oral squamous cell carcinoma.

The purpose of the present study was to identify site-specific prognostic biomarkers in patients with oral squamous cell carcinoma (OSCC). For this purpose, Epidermal growth factor receptor (EGFR), Stat3, H-ras, c-myc, p53, cyclin D1, p16, Rb and Bcl-2 were localized immunohistochemically in buccal mucosa carcinoma (n=74) and tongue carcinoma (n=61) patients. Expression of markers was compared between buccal mucosa and tongue carcinoma and assessed for their prognostic value in site-specific manner. On comparison, only cyclin D1 showed significant difference in expression with higher accumulation in tongue tumors (r=+0.177, p=0.039). Moreover, univariate survival analysis showed that in buccal mucosa patients, loss of p16 and overexpression of H-ras were significant prognosticators for relapse-free survival (RFS) and overall survival (OS), respectively. However, in Cox multivariate analysis, they lost their significance after adjusting for significant clinicopathological parameters. On the other hand, in tongue cancer patients, Cox multivariate analysis showed that for RFS, Stat3 and c-myc, and for OS, Stat3, Bcl-2 and p53 were significant prognosticators after adjusting for significant confounding factors. Our findings indicated that buccal mucosa and tongue carcinoma exhibit different biological behavior which is reflected in prognosis. Therefore, this approach might be helpful to precisely identify patients for more effectively tailored treatment strategy.

Early sexual maturity in local boars of Northeastern India: age-related changes in testicular growth, epididymal sperm characteristics and peripheral testosterone levels.

The present study reports the age related changes in the peripheral testosterone levels, testicular and epididymal growth and development and cauda epididymal spermiogram in local pigs of Northeastern India, which attain sexual maturity around 3 months of age. Local boars (n = 20) were castrated at monthly intervals from 2 to 6 months of age (4 boars per month) to study the testicular growth and development and the epididymal spermiogram. Blood samples, collected from local boars (n = 6) at monthly intervals from 2 to 6 months of age, were analyzed for testosterone levels by radioimmunoassay. Compared to Hampshire boars, significantly (P < 0.05) high testosterone levels were observed in the local boars as early as 2 months of age. The mean (± SEM) level of testosterone in the local boars at 2, 3 and 4 months of age was 11.89 ± 1.52, 20.45 ± 1.33 and 20.38 ± 2.0 ngml(-1), respectively. Though there was consistently significant (P < 0.05) difference in the body weight between Hampshire and local pigs, the same was not observed in case of testicular weight except at 3 and 6 months of age. In line with the above observation, the testis:body weight ratio (gram testis per kg body weight) was significantly (P < 0.05) higher in the local boars compared to the Hampshire boars at any time of observation, which ranged from 0.8 to 1.0 in case of Hampshire and from 2.3 to 3.0 in local boars. The sperm concentration in the cauda epididymal fluid of local boars at 2, 3 and 6 months of age was 2255 ± 186.6, 3685 ± 103.8 and 4325 ± 146.2 million/ml, respectively and the sperm motility, viability and total abnormality was 73.3, 75.2 and 6.2%, respectively at 3 months of age. Taken together, the testosterone level, testicular growth and development and epididymal spermiogram indicate the trait of early sexual maturity in the local pigs as compared to Hampshire.

Character and spatial distribution of OH/H2O on the surface of the Moon seen by M3 on Chandrayaan-1.

The search for water on the surface of the anhydrous Moon had remained an unfulfilled quest for 40 years. However, the Moon Mineralogy Mapper (M3) on Chandrayaan-1 has recently detected absorption features near 2.8 to 3.0 micrometers on the surface of the Moon. For silicate bodies, such features are typically attributed to hydroxyl- and/or water-bearing materials. On the Moon, the feature is seen as a widely distributed absorption that appears strongest at cooler high latitudes and at several fresh feldspathic craters. The general lack of correlation of this feature in sunlit M3 data with neutron spectrometer hydrogen abundance data suggests that the formation and retention of hydroxyl and water are ongoing surficial processes. Hydroxyl/water production processes may feed polar cold traps and make the lunar regolith a candidate source of volatiles for human exploration.

Comparative study of efficacy and toxicities of cisplatin vs vinorelbine as radiosensitisers in locally advanced head and neck cancer.

INTRODUCTION: Currently, concomitant chemoradiation using cisplatin is one of the standards of care for the management of head and neck cancer, but at the cost of increased acute toxicity. Our aim was to assess whether vinorelbine was less toxic and of at least comparable efficacy, if not better, compared with cisplatin. MATERIALS AND METHODS: A total of 72 patients with squamous cell carcinoma in the head and neck region were recruited, 40 in arm A and 32 in arm B. Patients in arm A received 40 mg/m2 cisplatin weekly. Patients in arm B received 6 mg/m2 vinorelbine weekly. Both arms also received 66 Gy of radiation in conventional fractionation. RESULTS AND ANALYSIS: There was no statistically significant difference in response rate or toxicities between the two arms, except for nausea and/or vomiting, which was significantly less frequent in the vinorelbine arm. CONCLUSION: Vinorelbine was as effective as cisplatin in controlling locoregional disease in locally advanced head and neck cancer, but was only marginally less toxic than cisplatin.

Molecular alterations in oral carcinogenesis: significant risk predictors in malignant transformation and tumor progression.

In this study an attempt was made to establish the significance of a battery of molecular alterations and thereby identify risk predictors in oral carcinogenesis. For this purpose, EGFR, Stat3, H-ras, c-myc, p53, cyclin D1, p16, Rb, Ki-67 and Bcl-2 were localized immunohistochemically in normal mucosa (n=12), hyperplasia (n=35), dysplasia (n=25), early stage carcinoma (n=65) and advanced stage carcinoma (n=70). Deregulation occurred at an early stage and the number of alterations increased with disease progression. Using multivariate logistic regression analysis, the significant risk predictor for hyperplasia from normal mucosa was Ki-67 (OR=5.75, p=0.021); the significant risk predictors for dysplasia from hyperplasia were EGFR (OR=12.96, p=0.002), Stat3 (OR=17.16, p=0.0001), p16 (OR=5.50, p=0.039) and c-myc (OR=5.99, p=0.052); the significant risk predictors for early stage carcinoma from dysplasia were p53 (OR=6.63, p=0.0001) and Rb (OR=3.81, p=0.056); and the significant risk predictors for further progression were EGFR (OR=5.50, p=0.0001), Stat3 (OR=4.49, p=0.0001), H-ras (OR=4.05, p=0.001) and c-myc (OR=2.99, p=0.015). Cyclin D1 holds a key position linking upstream signaling pathways to cell cycle regulation. Gene products of the mitogenic signaling pathway play an equally significant role as cell cycle regulatory proteins in the hyperplasia-dysplasia-early-advanced-carcinoma sequence and together may provide a reference panel of markers for use in defining premalignant lesions and predicting the risk of malignant transformation and tumor progression.

Mathematical modeling for the evaluation of zinc removal efficiency on clay sorbent.

The adsorption characteristics of zinc ion from aqueous solution on the lateritic clay were investigated through batch and column mode of operation. The system variables were optimized to evaluate the maximum extent of zinc adsorption as well as for the purpose of modeling. A model equation correlating zinc adsorption with input concentration was described. The adsorption behavior can well be described by Freundlich isotherm model rather than Langmuir isotherm model. The favorable and spontaneous nature of adsorption was indicated from the thermodynamical parameters. The capacity was determined from isotherm parameters in batch mode and breakthrough parameters in column mode. The bed depth service time (BDST) model was utilized to predict column efficiency corresponding to different bed heights. Elution performance of retained zinc, using HNO(3) of definite composition, was examined from elution profile. Efficiency of the process was determined through repetitive operation cycles of retention and elution. Effectiveness of the process was judged through estimation of efficiency versus the cost of operation.

Stat3 expression in oral squamous cell carcinoma: association with clinicopathological parameters and survival.

The present study sought to explore the occurrence of signal transducer and activator of transcription 3 (Stat3) in patients with oral squamous cell carcinoma (n=135) and its potential relationship with clinicopathological parameters and survival. Stat3 expression was studied by immunohistochemistry. Cytoplasmic or nuclear localization of Stat3 was observed in 62% of patients, whereas only nuclear Stat3 expression was found in 44%. Stat3 positivity in early-stage patients was 45% compared to 79% in advanced-stage patients. However, early-stage Stat3-positive patients showed a gradual increase in staining intensity, with intense staining seen in 52% of the tumors compared to 18% in Stat3-positive advanced-stage patients, where a gradual decrease in intensity expression was observed (p=0.001). Stat3 showed a significant positive correlation with disease stage (p=0.001), nodal status (p=0.033) and tumor size (p=0.001). Multivariate survival analysis using the Cox proportional hazard regression model showed that nuclear Stat3 was a significant independent prognosticator for both relapse-free survival (p=0.014) and overall survival (p=0.042) in early-stage patients. Our results indicated that Stat3 activation is an early event in oral squamous cell carcinoma and represents a potential risk factor for poor prognosis in early-stage patients.

p53 expression in leukoplakia and carcinoma of the tongue.

There is growing interest in assessing multistep carcinogenesis and predicting its course using different molecular markers. TP53 is a tumor suppressor gene and appears to be one of the molecular targets of tobacco-related carcinogens in oral cancer. The present study evaluated the role of p53 expression in patients with leukoplakia and carcinoma of the tongue. p53 expression was studied by immunohistochemistry. All patients with leukoplakia of the tongue were male tobacco users. Nuclear staining of p53 was observed in 79% of those patients. Fifty percent, 25% and 4% of the patients expressed 1+, 2+ and 3+ nuclear staining, respectively. When leukoplakia patients were graded according to histopathology, 67% had hyperplasia and 33% had dysplasia. Nuclear p53 accumulation was 88% in hyperplasia and 62% in dysplasia. In patients with tongue cancer, nuclear accumulation of p53 was seen in only 19% of the tumors, with a staining intensity of 1+ in 13%, 2+ in 2% and 3+ in 4% of the tumors. The prevalence of nuclear p53 positivity (79%) was significantly higher in patients with leukoplakia than in patients with tongue cancer (19%; chi2 = 34.32, r = -0.45, df = 1, p = 0.0001; odds ratio (OR) = 16.66, 95% CI, 5.25-52.86). Therefore, leukoplakia patients who show p53 expression have a higher risk of developing tongue cancer than those who do not show p53 expression. As the percentage of positivity of nuclear p53 was very low, none of the clinicopathological parameters or disease status showed any significant association with it. The interesting finding is that none of the female cancer patients showed nuclear p53 expression. Therefore, p53 accumulation is believed to be an early event in neoplastic progression of the tongue.

Evaluation of results of radiotherapy alone vs combined surgery and postoperative radiotherapy in carcinoma external auditory canal-10 years review.

Forty-one patients of external auditory canal (EAC) cancer attended the Department of Radiotherapy (RT), Medical College Hospital, Kolkata during the period from 1987 to 1996. Majority were above 50 years of age with slight female preponderance. Out of 41 patients 36 patients completed the full course of treatment of which 12 patients underwent combined modality treatment (RT 50-55 Gy plus surgery) and 24 patients received primary RT alone (55-60 Gy). Radiation therapy was given in standard fractionation schedule. Retrospective analysis revealed complete response in 8/12 (66.7%) in combined modality treatment group and in 3/24 (12.5%) in RT alone group. The actuarial 2 year survival was 19%. following RT alone, 85% following combined modality, 70% in early lesions and 18% in advanced lesions. The study suggests, surgical resection followed by postoperative irradiation is an effective method and better treatment option than RT alone as primary treatment modality for carcinoma of EAC.

Probing the pore of the auditory hair cell mechanotransducer channel in turtle.

Hair cell mechano-electric transducer (MET) channels play a pivotal role in auditory and vestibular signal detection, yet few data exist regarding their molecular nature. Present work characterizes the MET channel pore, a region whose properties are thought to be intrinsically determined. Two approaches were used. First, the channel was probed with antagonists of candidate channel subtypes including: cyclic nucleotide-gated channels, transient receptor potential channels and gap-junctional channels. Eight new antagonists were identified. Most of the effective antagonists had a partially charged amine group predicted to penetrate the channel pore, antagonizing current flow, while the remainder of the molecule prevented further permeation of the compound through the pore. This blocking mechanism was tested using curare to demonstrate the open channel nature of the block and by identifying methylene blue as a permeant channel blocker. The second approach estimated dimensions of the channel pore with simple amine compounds. The narrowest diameter of the pore was calculated as 12.5 +/- 0.8 A and the location of a binding site approximately 45% of the way through the membrane electric field was calculated. Channel length was estimated as approximately 31 A and the width of the pore mouth at < 17 A. Each effective antagonist had a minimal diameter, measured about the penetrating amine, of less than the pore diameter, with a direct correlation between IC(50) and minimal diameter. The IC(50) was also directly related to the length of the amine side chains, further validating the proposed pore blocking mechanism. Data provided by these two approaches support a hypothesis regarding channel permeation and block that incorporates molecular dimensions and ion interactions within the pore.

Walking in a vacuum-assisted socket shifts the stump fluid balance.

Gains in stump volume have been documented in trans-tibial amputees while walking in custom made under-sized, total surface-bearing, vacuum-assisted sockets (Board et al., 2001). These gains raised doubts as to whether the sockets were truly under-sized and concerns that using an over-sized socket with vacuum-assist could lead to swelling, resulting, in discomfort or pain. The purposes of the present study were to determine if: (a) walking in a vacuum-assisted socket causes the stump to retain or gain volume in excess of the available socket volume and (b) the resulting increase in stump volume with an over-sized socket causes discomfort, pain, and/or the skin to redden. The results of this study showed the stump retained or gained volume in excess of the available socket volume while walking in vacuum-assisted sockets of various sizes. The stump lost less volume than predicted, or gained volume, in under-sized sockets. It also gained more volume than predicted in over-sized sockets. No discomfort, pain, or skin reddening, resulting from the volume gain was reported by any of the subjects after walking in an over-sized socket. This change in fluid balance towards a net gain supports the findings by Board et al. (2001) that vacuum-assist ensures a good fit during the day in ambulatory trans-tibial traumatic amputees with mature stumps.