Evaluation of chikungunya virus infection in children from India during 2009-2010: A cross sectional observational study.

Chikungunya virus, a small (about 60-70 nm diameter), spherical, enveloped, positive, single stranded RNA virus is transmitted by Aedes mosquitoes. After a short period of incubation (3-5 days) symptoms like fever with joint pains and others start appearing. After a gap of 20 years, this virus re-emerged during 2006-2008 in India causing a major outbreak of CHIKV in India. This study was conducted subsequent to the major outbreak in order to evaluate the proportion of chikungunya virus infection in children with suggestive symptoms at three geographical locations of India. Lineage of circulating strains and changes in the E1 structural polypeptide were also determined. Blood samples were collected (in Sodium citrate vacutainer tubes) during 1st June 2009 to 31st May 2010 from children (age 0 ≤ 18 years) suspected to have chikungunya infection, that is, those who presented with sudden onset of fever and/or joint pain, myalgia, and headache from three regions of India, All India Institute of Medical Sciences (AIIMS) in New Delhi, Karnataka Institute of Medical Sciences (KIMS) in Hubli and Sawai Mansingh Medical College (SMS) in Jaipur. Detection of CHIKV antibodies in all acute-phase patient plasma samples was done by IgM ELISA and for samples within ≤5 days of fever, a one-step RT-PCR was carried out on a block thermo-cycler targeting 294 bp region of E1 gene that codes for the viral envelope protein. Comparison of nucleotide and amino acid sequences from few positive samples of two regions was done with African S-27 reference strain using BioEdit. A phylogenetic tree was constructed using MEGA 6 by using the Maximum Likelihood method based on the Kimura 2-parameter model. Out of the 723 acute phase samples tested from three geographical locations of India, Chikungunya virus infection was detected in 249/723 (34.44%) subjects by either IgM Elisa (180/723) or RT-PCR (69/412). RT-PCR was employed in samples collected from children with ≤5 days of fever. Maximum positive cases were from KIMS center, Hubli. Seasonally, positivity varied with number of enrolled cases at KIMS and SMS. Joint pain was significantly associated with CHIKV positivity (P = 0.0156). Presence/absence of certain clinical features varied with age (P < 0.05). Sequence analysis revealed four amino acid changes. Phylogenetic analysis with partial sequences of E1 gene from KIMS (n = 12) and SMS (n = 5) showed that the study isolates clustered with Indian Ocean Lineage strains (IOL) of East, Central and South African (ECSA) type. Evaluation of chikungunya virus infection in children from India during 2009-2010 showed high proportion of CHIKV infection in Southern region of India compared to Northern region. The circulating CHIKV strains were of Indian Ocean Lineage (IOL) group within the East, Central, and South African (ECSA) genotype. However few amino acid changes were observed in E1 polypeptide with reference to African strain S-27 (AF369024). Further studies are needed to know the implications of these changes in vector-pathogen compatibility and host-pathogen interactivity. As a whole, this study highlighted the proportion of CHIKV cases, lineage of causative strain and evolutionary pattern of circulating strain in terms of amino acid changes in the structural protein.

Expression of DNA methyltransferases 1 and 3B correlates with EZH2 and this 3-marker epigenetic signature predicts outcome in glioblastomas.

This study aims to analyze expression of EZH2 and DNA-methyltransferases (DNMT1, 3A and 3B) in astrocytic tumors and investigate their link as well as their correlation with survival, especially in GBMs. Expression of EZH2 and DNMTs (DNMT1, DNMT3A and DNMT3B) in different grades of astrocytomas (n=93) was assessed by qRT-PCR and immunohistochemistry. GBM-U87MG cell line was used for functional studies. Strong immunopositivity (LI≥25%) for EZH2, DNMT1 and DNMT3B was detected in 52%, 56% and 64% cases of GBMs respectively, which was significantly higher as compared to Grade II/III cases. Similarly, their median fold change of mRNA expression was also significantly higher in GBMs. There was also a significant positive correlation between DNMT1/DNMT3B and EZH2 mRNA and protein expression, which was in concordance with TCGA data set. Inhibition of DNMTs in cell line by Azacytidine resulted in down-regulation of EZH2, while knock-down of EZH2 by siRNA was not associated with any significant alteration of DNMTs, indicating that EZH2 expression in GBMs is possibly regulated by DNMTs, but not the reverse. Strong immunopositivity for EZH2, DNMT1 and DNMT3B were individually associated with significantly shorter survival and showed no correlation with IDH1 mutation status. In addition, the combination of these 3 markers represented an independent prognostic signature with cases having weak/negative expression of all 3 markers being associated with best prognosis. For the first time, the present study describes an epigenetic prognostic signature in GBMs based on immunohistochemical expression of EZH2, DNMT1 and 3B which can be used easily in routine neuropathology practice.

O-arm with navigation versus C-arm: a review of screw placement over 3 years at a major trauma center.

INTRODUCTION: There is a relatively high incidence of screw misplacement during spinal instrumentation due to distortion of normal anatomy following spinal trauma. The O-arm is the next-generation spinal navigation tool that provides intraoperative 3-D imaging and navigation for spine surgeries. AIMS AND OBJECTIVES: To evaluate and compare the use of O-arm as compared to C-arm for spinal trauma in a Level I trauma center in India. MATERIALS AND METHODS: In this retrospective study over 3 years (July 2010-April 2013), All patients of spinal injury who underwent spinal instrumentation were divided into O-arm group and C-arm group. Accuracy of screw placement was assessed during each surgery in both groups. RESULTS: A total of 587 patients were evaluated during the study period. There were 278 patients in O-arm group and 309 patients in C-arm group. Both groups were well matched in mean age (27.7 vs. 28.9 years), ASIA grades, and level of injury. The number of screws placed was significantly higher in the C-arm group as compared to the O-arm group (2173 vs. 1720). However, the O-arm group had significantly less screw malplacement rate of 0.93% (n = 16) as compared to malplacement rate in C-arm group of 8.79% (n = 191, p < 0.05). CONCLUSION: Use of O-arm imaging system ensures accurate screw placement and dramatically decreases screw malplacement rate, thus providing better patient safety. Its use is especially beneficial in academic and teaching centers where novice surgeons can attain results equivalent to that of experts in spinal instrumentation.

Genome-wide small noncoding RNA profiling of pediatric high-grade gliomas reveals deregulation of several miRNAs, identifies downregulation of snoRNA cluster HBII-52 and delineates H3F3A and TP53 mutant-specific miRNAs and snoRNAs.

Pediatric high-grade gliomas (HGGs) are highly malignant tumors that remain incurable and relatively understudied. The crucial role of noncoding RNAs (ncRNAs) has been reported in various cancers. However, the study on miRNAs in pediatric HGGs is scant and there is no report till date on the status of other small ncRNAs. Genome-wide microarray analysis was performed to investigate small ncRNA expression in pediatric HGG (n = 14) and compared to adult glioblastoma (GBM) signature. The validation of miRNAs and small nucleolar RNAs (snoRNAs) was done by real-time polymerase chain reaction. TP53 and H3F3A mutation-specific miRNA and snoRNA profiles were generated and analyzed. Pediatric HGGs showed upregulation of miR-17/92 and its paralog clusters (miR106b/25 and miR-106a/363), whereas majority of downregulated miRNAs belonged to miR379/656 cluster (14q32). Unsupervised hierarchical clustering identified two distinct groups. Interestingly, Group 2 with downregulated 14q32 cluster showed better overall survival. The miRNAs unique to pediatric HGG as compared to adult GBM were predicted to affect PDGFR and SMAD2/3 pathways. Similarities were seen between pediatric HGG and TP53 mutant miRNA profiles as compared to wild types. Several of H3F3A mutation-regulated genes were found to be the targets of H3F3A mutant-specific miRNAs. Remarkably, a significant downregulation of HBII-52 snoRNA cluster was found in pediatric HGGs, and was specific to H3F3A nonmutants. This is the first genome-wide profiling study on miRNAs and snoRNAs in pediatric HGGs with respect to H3F3A and TP53 mutations. The comparison of miRNA profiles of pediatric HGGs and adult GBM reiterates the overlaps and differences as also seen with their gene expression and methylation signatures.

Association of TLR4 polymorphisms with Mycobacterium avium subspecies paratuberculosis infection status in Canadian Holsteins.

Mycobacterium avium ssp. paratuberculosis (MAP) causes chronic enteritis in cattle that results in substantial financial losses to the cattle industry worldwide. Given that susceptibility to MAP infection is determined in part by genetics, marker-assisted selection may help in the breeding of animals that are more resistant to MAP infection. The toll-like receptor 4 gene (TLR4) was selected as a potential candidate gene because of its role in innate immunity and its involvement in MAP recognition and infection. The objective of this study, therefore, was to identify associations between TLR4 polymorphisms and susceptibility to MAP infection in Canadian Holstein cows. Two biologically relevant SNPs, including c.-226G>C in the 5'-untranslated region and the non-synonymous SNP c.2021C>T in the potential TIR domain, were selected for an association analysis with MAP infection status in 409 Canadian Holsteins. The haplotype C-T from these combined SNPs yielded significant association with susceptibility to MAP infection, supporting the involvement of TLR4 in susceptibility to MAP infection.

EZH2 expression in gliomas: Correlation with CDKN2A gene deletion/ p16 loss and MIB-1 proliferation index.

Enhancer of zeste homolog 2 (EZH2) mediated down-regulation of CDKN2A/p16 has been observed in cell lines as well as in a few carcinomas. However, there is no study correlating EZH2 expression with CDKN2A/p16 status in gliomas. Hence, the present study was conducted to evaluate EZH2 expression in astrocytic and oligodendroglial tumors and correlate with CDKN2A/p16 status as well as MIB-1 labeling index (LI). Gliomas of all grades (n = 118) were studied using immunohistochemistry to assess EZH2, p16 and MIB-1 LI and fluorescence in situ hybrization to evaluate CDKN2A gene status. EZH2 expression and CDKN2A homozygous deletion (HD) were both significantly more frequent in high-grade gliomas (HGG). Further, strong EZH2 expression (LI ≥ 25%) was significantly more common in HGGs without CDKN2A HD (48.7%; 19/39) as compared to cases with deletion (15.8%; 3/19). Loss of p16 expression was noted in 100% and 51.3% of CDKN2A deleted and non-deleted tumors, respectively. Notably, 80% (16/20) of the CDKN2A non-deleted HGGs with p16 loss had strong EZH2 expression, in contrast to only 15.8% (3/19) in the deleted group. Loss of p16 expression significantly correlated with MIB-1 LI, irrespective of EZH2 status. Thus, this study shows that EZH2 expression correlates with tumor grade in both astrocytic and oligodendroglial tumors and hence can be used as a diagnostic marker to differentiate between low and HGGs. Further, this is the first report demonstrating an inverse correlation of strong EZH2 expression with CDKN2A HD in HGGs. Loss of p16 protein expression is mostly attributable to CDKN2A HD and correlates significantly with MIB-1 LI. Notably, our study for the first time suggests a possible epigenetic mechanism of p16 loss in CDKN2A non-deleted HGGs mediated by strong EZH2 expression. A hypothetical model for control of proliferative activity in low versus HGGs is therefore proposed.

Pediatric giant pituitary adenomas: are they different from adults? A clinical analysis of a series of 12 patients.

OBJECTIVES: To evaluate clinical presentation and microsurgical outcome of giant pituitary adenomas (GPAs) in pediatric age. METHODS: All patients <18 years, who were operated on at our center for GPA (tumor >40 mm in maximum diameter) were included in study. Clinical features, hormonal profile, radiology, surgical approach, results and complications were analysed. RESULTS: A total of 12 children with GPA were managed microsurgically. Visual deterioration (73 %) was most common presentation. Functioning adenomas were found in 83 % patients, with prolactinomas being most common. Twelve patients underwent a total of 16 microsurgical procedures, with a single surgery done in eight (75 %) patients. Out of the 12 primary surgeries, eight (67 %) were performed trans-sphenoidally. A near-total excision (>90 % tumor removal) could be achieved in six (50 %) patients. Visual improvement was observed in 44 % patients. However, there was no improvement in those where the eye was negative to perception of light prior to surgery. At the last follow-up, all the patients with functioning adenomas were in hormonal remission, and there was no residual/recurrent tumor in patients with non-functional adenomas. 25 % experienced single or multiple perioperative or postoperative complications. There was one perioperative death (8 %). CONCLUSIONS: GPAs are very rare in the pediatric population, with majority being functional and more aggressive in nature as compared to in adults. However, most of them can be approached trans-sphenoidally. The combination of surgery and radiotherapy, as well as medical therapy with bromocriptine, achieves good tumor control, despite a high rate of residual tumor and tumor recurrence.

Prognosis of MGMT -Positive Gene in Patients with Brain Tumors of Grade III and Grade IV.

Sumit GoyalObjective To evaluate MGMT gene positivity is associated with better survival in patients diagnosed with brain tumor World Health Organization (WHO) grades III and IV Material and Methods Single-institute restrospective study. A total of 80 patients were enrolled, all underwent surgery either total or subtotal excision of the tumor and MGMT gene testing on tumor tissue by RT-PCR. All received adjuvant radiation (60 Gy/30 fractions, 5 fractions/week) with concurrent temozolomide (75 mg/m 2 ), followed by 12 cycles of adjuvant temozolomide (150 mg/m 2 1st cycle followed by 200 mg/m 2 ) with regular follow-up. Results A total of 80 patients, 75 underwent subtotal excision, 27 were WHO grade III vs. 48 WHO grade IV. Five underwent total excision 1 was WHO grade III vs. 4 WHO grade IV. The median PFS and OS in five patients in total excision in grade III patient was 9.0 and 20 compared with Grade IV, where the median PFS and OS was 8.8 and 17.8 months. Out of 75 patients in the subtotal group median PFS and OS, respectively, in Grade III group was 9.1 and 19.3 and, WHO grade IV with median PFS of 8.8 and OS of 18.8. Conclusion MGMT gene positivity is a prognostic factor in grade III and IV brain tumor.

Fungal thalamic abscess caused by Rhinocladiella mackenziei in an immunocompetent patient.

Cerebral phaeohyphomycosis (CP) stands as an exceedingly uncommon yet severe type of fungal infection affecting the central nervous system, attributable to dematiaceous fungi. Despite the patient's immune status, CP is associated with grave prognosis. In the present study, authors describe the first case of left thalamic fungal abscess due to Rhinocladiella mackenziei in an immunocompetent 39-year-old male patient in Jaipur, Rajasthan. Early diagnosis by direct microscopy of aspirated pus and extensive management with surgical excision and prolonged antifungal coverage showed favourable outcome. The present case is one of the few cases documented globally who has survived.

Role of simvastatin in prevention of vasospasm and improving functional outcome after aneurysmal sub-arachnoid hemorrhage: a prospective, randomized, double-blind, placebo-controlled pilot trial.

BACKGROUND: Vasospasm plays a major role in the morbidity and mortality after aneurysmal subarachnoid hemorrhage (aSAH). The preliminary studies suggest that statins protect against cerebral vasospasm. OBJECTIVE: The aim of the study was to determine the role of simvastatin in preventing clinical vasospasm and improving functional outcome in patients with aSAH. METHODS: All patients with aSAH admitted within 96 h of ictus were randomized to receive either Simvastatin or placebo - 80 mg/day for 14 days. Thirty eight patients were recruited in the study- 19 received Simvastatin and 19 placebo. All the patients underwent surgical clipping of the aneurysm. The primary outcome of the study was the development of clinical cerebral vasospasm. The secondary outcomes included Glasgow Outcome Score (GOS), Modified Rankin Scale (MRS) and Barthel Index Score (MBI) at follow-up at 1, 3 and 6 months. RESULTS: 16% of the patients in the simvastatin group had high Middle Cerebral Artery velocities (> 160 cm/sec) on transcranial Doppler on one or more than one day during the study duration as compared to 26% of the patients in the placebo group (p = 0.70). Neurological deterioration occurred in 26% and 42% of the patients in simvastatin group versus placebo group, respectively (p = 0.31). There was an improvement in the functional outcome in the simvastatin group at 1, 3 or 6 months in the follow-up; however, this difference was not statistically significant. CONCLUSIONS: There was benefit of simvastatin in terms of reduction in clinical vasospasm, mortality or improved functional outcome, however, this was not statistically significant.

Spinal dural arterio-venous fistula: clinico-radiological profile and outcome following surgical occlusion in an Indian neurosurgical center.

BACKGROUND: Spinal dural arteriovenous fistula (SDAVF) is a common type of spinal vascular lesion. However, there has not been any published study on its clinico-radiological characteristics or surgical outcome from India. AIM: The aim of this study was to determine the clinico-radiological features of patients with SDAVF, outcomes following surgical ligation of the fistula and the various factors involved. MATERIALS AND METHODS: Patients who were operated for SDAVF were studied for demographic details, symptoms, clinical severity, radiological features and neurological outcome in the form of improvement in gait disability grades. Appropriate statistical tests were performed. RESULTS: There were 22 (19 males, 3 females) patients of SDAVF who underwent surgical ligation with a mean age of 55 years. The mean duration of symptoms at presentation was 15 months. Three patients had acute onset while the rest had insidious onset of symptoms. Out of the 22 patients, 11 (50%) had motor weakness as the first symptom, 13 (59%) were bedridden and 19 (86.4%) had bladder involvement at presentation. Thirteen patients had fistulae in thoracic spine, whereas eight had fistulae in the lumbar spine. All had a favorable outcome in the form of at least non-progression of gait disability (14 had improvement while 8 had stabilized). The improvement was non-significantly associated with younger age, acute onset, ambulant status and fistula below T9. It was inversely associated with pain as the first symptom and fluctuant clinical course. CONCLUSION: Surgical occlusion of SDAVF is usually associated with either improvement or stabilization of motor weakness.

Monitored gradual occlusion of the internal carotid artery followed by ligation for giant internal carotid artery aneurysms.

OBJECTIVE: To demonstrate a technique of gradual monitored occlusion of the internal carotid artery (ICA) followed by ligation for giant aneurysms as an option for balloon test occlusion followed by permanent ligation of ICA. MATERIALS AND METHODS: Authors retrospectively analyzed 27 patients with giant and complex ICA aneurysms who underwent carotid artery ligation between January 2001 and December 2010. Clinical presentation included headache, vision loss and diplopia. There were 19 patients with cavernous aneurysm, 5 supraclinoid, 1 ophthalmic, 1 petrous segment and 1 cervical segment aneurysm located extracranially. All demonstrated good cross-circulation. Selverstone clamp was used for gradual occlusion of the ICA over 72 h under closed observation in the intensive care unit. RESULTS: Six patients developed hemiparesis in the postoperative period. Improvement occurred in one patient over two to three weeks while the remaining five patients had residual hemiparesis. One patient developed malignant MCA infarct for which decompressive craniectomy had to be done. There was no mortality in the present series. CONCLUSIONS: Gradual monitored occlusion and ICA ligation may be a simple, safe alternative procedure to clipping in surgically inaccessible and complex aneurysms, especially for surgeons with limited experience. Cross circulation study is an absolute requisite for carotid ligation.

AYUSH 64, a polyherbal Ayurvedic formulation in Influenza-like illness - Results of a pilot study.

BACKGROUND: Influenza-like Illness (ILI) refers to a wide range of viral infections with an important cause of morbidity and mortality worldwide. The global incidence of ILI is estimated at 5-10% in adults and 20-30% in children. In India influenza accounts for 20-42% of monthly acute medical illness hospitalizations during the peak rainy season. AYUSH-64, a poly-herbal drug, is in practice for 40 years for various clinical conditions like fevers, microfilaremia, and inflammatory conditions. OBJECTIVE: A pilot study was conducted to evaluate the safety and efficacy of Ayurvedic formulation, AYUSH-64 in clinically diagnosed ILI for accelerating the recovery. MATERIAL AND METHODS: A prospective, open-label, nonrandomized, single group, single-center pilot clinical study with pre-test and post-test design was conducted at Raja Ramdeo Anandilal Podar Central Ayurveda Research Institute for Cancer, Mumbai, an institute of Central Council for Research in Ayurvedic Sciences (CCRAS) between June 2018 and July 2019. A total of 38 participants of clinically diagnosed ILI (18-65 years) were studied with an one-week intervention of 'AYUSH 64' in a dose of 3 gm/day and three weeks post-treatment observation period. Assessment of parameters viz. improvement in the symptoms of ILI, frequency of usage of acetaminophen, antihistaminic and cough syrup, hematology, liver function and kidney function tests along with incidence of secondary complications, and time to return to a normal routine was done. RESULTS: One-week intervention of AYUSH 64 helped to recover from ILI symptoms with reduced frequency of usage of acetaminophen and antihistaminic. The intervention was safe on hematology and biochemical parameters. No serious adverse effects were observed during the study. CONCLUSION: AYUSH 64 along-with standard care in ILI is safe and efficacious and this may be used in other viral infections with pyrexia as add-on to standard care for early recovery and better outcome.

Microsurgical management of prolactinomas - clinical and hormonal outcome in a series of 172 cases.

AIMS AND OBJECTIVES: To report hormonal outcome after surgery in a special subgroup of prolactinomas in whom medical therapy is not effective or not indicated. PATIENTS AND METHODS: All patients who underwent surgery for prolactinomas, between December 2002 and December 2009, were analyzed retrospectively. The study group consisted of patients who were either intolerant or noncompliant to dopamine agonist (DA) therapy or those in whom medical treatment could not be given due to various reasons. The surgical results were assessed according to whether patients had microadenoma (<1 cm diameter), macroadenoma (>1 cm diameter), or giant prolactinoma (>4 cm diameter). Initial and final hormonal remission was defined as normalization of serum prolactin levels (<25 ng/ml) at 7 days after surgery and at last follow up, respectively. RESULTS: Of the 172 patients, 133 (77%) were operated by primary transsphenoidal approach and 25 (14.5%) were operated transcranially and 14 patients required reoperation, either transsphenoidally (6 patients) or transcranially (8 patients). Overall, at last follow-up, hormonal remission could be achieved in 44% patients (83% microadenomas, 48% macroadenomas, and 16% of giant adenomas). There were three deaths (1.7%), 12 patients (7%) had single/multiple postoperative treatable complications. 59% of those patients, who did not achieve remission after surgery, finally attained normoprolactinemia with either DA therapy or radiotherapy, at last follow-up. CONCLUSIONS: Medical treatment of prolactinomas with DA should be considered as treatment of choice for these tumors. However, there is a major subgroup of patients who respond better to surgery rather than protracted medical therapy.

Yoga Therapy as an Adjuvant in Management of Asthma.

OBJECTIVE: To assess the effect of yoga on control of asthma in children with bronchial asthma. METHODS: This hospital-based interventional randomized controlled trial conducted in the Department of Pediatrics at a tertiary care center of North India from November 2017 to October 2018 enrolled 140 newly diagnosed cases of asthma of age 10-16 y who were randomly divided into two groups. Seventy children in the case group practiced yoga under supervision for a period of 3 mo in addition to pharmacological treatment. Seventy controls received only pharmacological treatment. Pulmonary-function tests were done at baseline, 6 wk, and 12 wk along with quality of life (QOL) assessment by Pediatric Asthma Quality of Life Questionnaire (PAQLQ). The outcome measures assessed were forced vital capacity (FVC), forced expiratory volume in one second (FEV1), FEV1/FVC and peak expiratory flow rate (PEFR). QOL evaluation was done in 3 domains: activity limitation, symptoms, and emotional function. RESULTS: The asthmatic children practicing yoga have shown significant improvement in FVC, FEV1, FEV1/FVC and PEFR which was better as compared to controls. Improvement was also noted in mean-PAQLQ score in cases which was statistically significantly better as compared to controls. CONCLUSION: Yoga appears to have significant positive effect on control of asthma measured by pulmonary-function test and QOL. Therefore yoga therapy can be recommended as an adjuvant in management of asthma along with standard pharmacological management.

Identification of single nucleotide polymorphisms in the bovine interleukin-12 and interleukin-23 receptor genes and their associations with health and production traits in Holstein cows.

Interleukin-12 (IL-12) and interleukin-23 (IL-23) are proinflammatory cytokines produced by macrophages and dendritic cells in response to infection with intracellular pathogens. The IL-12 receptor (IL-12R) is a heterodimer composed of 2 subunits, ß1 and ß2. The IL-23 receptor (IL-23R) is a heterodimer composed of the IL-12Rß1 subunit and a unique IL-23R subunit. Given the importance of IL-12 and IL-23 for modulating inflammation and the host immune response, the IL-12 and IL-23 receptor genes may be suitable candidate genes for studying disease resistance in dairy cattle. We hypothesize that single nucleotide polymorphisms (SNP) exist within these genes and that they contribute to variation in health and production traits in dairy cattle. To investigate this, a selective DNA pool was constructed using bull semen based on the estimated breeding values for somatic cell score (SCS), an indicator trait used to achieve genetic improvement for resistance to mastitis. Gene segments were amplified from this pool by PCR and the amplicons were sequenced to reveal SNP. A total of 10 SNP, including 2 in IL-12Rß1, 5 in IL-12Rß2, and 3 in IL-23R were identified. The SNP (n=5) were found in the 5' untranslated region (UTR) putative promoter regions of the genes, and SNP IL-23R c.1714A>C was a nonsynonymous SNP. Canadian Holstein bulls (n=492) were genotyped using Sequenom MassARRAY (Sequenom Inc., San Diego, CA). No association was found with SCS based on bull deregressed estimated breeding values for SCS; however, associations of SNP in the IL-12Rß2 gene (c.-511A>G, c.87A>G, c.2957A>C) were found with milk and protein yield. Further investigation will be required to elucidate the biological and practical relevance of these SNP.

Giant pituitary adenomas--an enigma revisited. Microsurgical treatment strategies and outcome in a series of 250 patients.

BACKGROUND: Giant pituitary adenomas (> 4 cm) are a surgical challenge. We present our experiences in surgical management of these tumors in a series of 250 patients. METHODS: Two hundred and fifty patients with giant pituitary adenomas were managed surgically at our center over last 13 years. Majority (92%) of patients presented with visual deterioration. Non-functioning tumors were found in 136 patients (54.3%). Among functioning adenomas, 63 patients (25.4%) had prolactinomas and 45 patients (18%) had GH-secreting adenomas; while 3 patients each had LH and ACTH- secreting adenomas. The maximum tumor diameter varied from 4 to 10.5 cm, with mean diameter of 5.4 cm. The factors determining choice of operative approach and surgical outcomes in these tumors were analyzed. RESULTS: Overall, 273 surgical procedures were performed in 250 patients. Of these, 110 were transsphenoidal, while 163 were transcranial approaches. A single surgical procedure was performed in 227 patients (89.2%). 23 patients (9.2%) underwent re-exploration either because of postoperative apoplexy or residual tumor. Overall, near total (>90%) tumor excision could be achieved in 74%, with improved vision in 53% and good outcome in 75% patients. The mortality and morbidity were 4.4% and 14%, respectively. CONCLUSIONS: The main goal of surgical treatment of giant pituitary adenoma is maximum possible tumor extirpation with minimal side effects, which can be achieved by careful preoperative planning of operative approach, based on directions of tumor extensions and invasiveness. Maximal surgical removal of giant adenomas offers best chances to control tumor growth when followed with adjuvant medical and radiation therapies.

Survival after a penetrating injury traversing midbrain - case report.

Penetrating civilian shrapnel injuries to brainstem are quite uncommon, but invariably fatal. We report a rare case of a child who survived following shrapnel injury to tectum of midbrain.