Hedgehog (Hh) signaling pathway is a valid therapeutic target in a wide range of malignancies. We focus here on glioblastoma multiforme (GBM), a lethal malignancy of the central nervous system (CNS). By analyzing RNA-sequencing based transcriptomics data on 149 clinical cases of TCGA-GBM database we show here a strong correlation (r = 0.7) between GLI1 and PTCH1 mRNA expression—as a hallmark of the canonical Hh-pathway activity in this malignancy. GLI1 mRNA expression varied in 3 orders of magnitude among the GBM patients of the same cohort showing a single continuous distribution—unlike the discrete high/low-GLI1 mRNA expressing clusters of medulloblastoma (MB). When compared with MB as a reference, the median GLI1 mRNA expression in GBM appeared 14.8 fold lower than that of the “high-Hh” cluster of MB but 5.6 fold higher than that of the “low-Hh” cluster of MB. Next, we demonstrated statistically significant up- and down-regulation of GLI1 mRNA expressions in GBM patient-derived low-passage neurospheres in vitro by sonic hedgehog ligand-enriched conditioned media (shh-CM) and by Hh-inhibitor drug vismodegib respectively. We also showed clinically achievable dose (50 μM) of vismodegib alone to be sufficient to induce apoptosis and cell cycle arrest in these low-passage GBM neurospheres in vitro. Vismodegib showed an effect on the neurospheres, both by down-regulating GLI1 mRNA expression and by inducing apoptosis/cell cycle arrest, irrespective of their relative endogenous levels of GLI1 mRNA expression. We conclude from our study that this single continuous distribution pattern of GLI1 mRNA expression technically puts almost all GBM patients in a single group rather than discrete high- or low-clusters in terms of Hh-pathway activity. That is suggestive of therapies with Hh-pathway inhibitor drugs in this malignancy without a need for further stratification of patients on the basis of relative levels of Hh-pathway activity among them.
Premise and Objective:Elective laparoscopic cholecystectomy (LC) has low risk for post-operative infectious complications; still most clinicians use persistent post-operative prophylactic antibiotics out of habit, tradition, or simply as defensive practice due to evolving medicolegal implications of a large number of surgeries being showcased as daycare or next day discharge procedures. This randomised prospective trial was done to test the need for such prophylaxis in cases of elective LC in a rural/semi-urban setting.Materials and Methods:Two hundred and ten successive patients undergoing elective LC were randomised into groups receiving single dose of injection ceftriaxone at the time of induction of anaesthesia, (Group A = 112 cases) and those who in addition to above received injection ceftriaxone twice daily for 2 days postoperatively (Group B = 98 cases). Post-operative infectious complications between two groups were compared for variables such as age, sex, body mass index and bile/stone spillage.Results:There was no significant difference in surgical site infection rates between the groups for variables such as age, sex, body mass index, duration of symptoms, American Society of Anesthesiologists grade, duration of surgery and hospital stay. Intraoperative spillage of stones (9.8% [A]: 5.1% [B]) did not increase infectious complications even in the presence of positive bile culture (Group A, N = 7 vs. Group B, N = 3). An operative time of greater than 60 min was found to be associated with increased surgical site infection (P = 0. 0006).Conclusion:Single dose of ceftriaxone at the time of induction is adequate prophylaxis following elective LC even in the rural/semi-urban Indian setting and routine continued administration of antibiotic should be abandoned as it contributes to adverse reactions, drug resistance and unnecessary financial burden.
Contrecoup injuries comprise a group of focal brain injuries that occur at areas distant from the point of impact. It has been hypothesized that patients with contrecoup injuries would have a worse outcome because of the diffuse nature of injury. At Nilratan Sircar Medical College, Kolkata, 74 patients presenting with contrecoup injuries over a period of 1 year were prospectively analyzed. Site of primary impact was determined by clinical and CT scan criteria. The age, modes of injury, Glasgow coma scale (GCS), site of injury, pattern of injury, and mortality were analyzed. Delayed presentation of contrecoup injury in patients who deteriorated over time was also noted in imaging. The presence of contrecoup injury implies that the traumatic forces have dissipated into the brain, and from the biomechanisms explained, the brain is likely to have suffered greater damage than the case in coup injury alone. The present study shows that the presence of contrecoup contusions is associated with a poor prognosis across all GCS and age categories.
Epidural hematoma (EDH) is a traumatic accumulation of blood between the inner table of the skull and the dural membrane. Contact-related skull deformation causes inbending or fracturing of cranium or both, leading to separation of the dura mater from inner table. This injures the dural arteries, veins, venous sinus, or diploid channels, producing EDH. They usually occur as a result of direct impact injuries to the head, ipsilateral to impact side. Incidence of epidural hematoma is 1 to 3% of all head injuries. Contrecoup EDH cases are rare. and because of its rarity, we present a case report of a 17-year-old boy with contrecoup EDH who sustained head injury due to road traffic accident. Computed tomography of the brain showed left occipital bone fracture and large contrecoup extradural hematoma in right frontal region associated with pneumocephalus and hemorrhagic contusional edema beneath it. The EDH was operated on, and the patient was discharged uneventfully.
Background: Endoscopic Endonasal Transphenoidal Pituitary Surgery (EETS), has been proved to be a preferred alternative to conventional surgery because of its salient features like wider, more panoramic field of visualization, improved illumination and mobility of instruments, and an ability to look around anatomical corners using angled lens and minimal invasiveness.The current study was done to analyse the effectiveness and morbidity in the patients operated in our centre by Endoscopic Endonasal Transphenoidal Pituitary Surgery (EETS) done by single team in single centre in15 months. Aims and Objective: To describe a case series of patients with pituitary adenomas with endoscopic endonasaltranssphenoidal approach, the technique performed and complications in our centre. Materials and Methods: The technique performed in a series of 30 consecutive patients, and description of their complications and the protocol followed to treat these complications. Results: The tumor removal was gross total in 18 (60.0%) patients, subtotal in 8 (30.7%), and partial in 4 (7.7%) patient. Two patients with growth hormone-secreting adenomas had normalization of hormonal status. Four patients developed temporary diabetes insipidus. Four patients developed post-operative CSF rhinorrhea and were managed conservatively.Two patient had recurrence of tumor.one patient had meningitis and one patient expired in perioperative periods. Conclusions: Our experience suggests that the Endoscopic transsphenoidal approach offers a potentially viable and cost economic treatment option in pituitary tumors which are difficult to remove by the standard microscopic approaches. In past one and half year we have witnessed encouraging results without much of the anticipated complications.
Encephalocele and craniosynostosis are known separate entities found clinically. While searching for a causal association between them, there has been a proposed justified hypothesis. Yet the two conditions are very rarely found in association. We have happened to find such a rare case which we treated and followed up for establishing the proposed theory of association between the two clinical entities.Asian Journal of Medical Sciences Vol.7(4) 2016 98-100
Primary spinal primitive neuroectodermal tumors (PNET) is a rare occurrence and carries a poor prognosis. A 13-year old female patient acutely presented with pain in the thoracic region, bilateral lower limb weakness, bladder and bowel dysfunction. Clinically paraplegia with truncal weakness, lower limb deep tendon reflexes of both side were absent and planter reflexes equivocal bilaterally. Preoperative MRI of thoracic spine revealed D4-D6 extradural SOL. A D4-D5 Laminectomy and left Cortico transversectomy done. Pathological findings were consistent with PNET. The clinical, histopathological, and radiological findings of the patient are presented.
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