Subarachnoid hemorrhage (SAH) due to intracranial aneurysm rupture is a complex clinical disease with high mortality and morbidity. Recent studies suggest that early brain injury (EBI) rather than vasospasm might be responsible for morbidity and mortality within 24-72 hours after SAH. The rise in intracranial pressure following SAH causes a significant drop in cerebral perfusion pressure that leads to global cerebral ischemia and initiates the acute injury cascade. Various molecular mechanisms have been shown to involve in the pathophysiology of EBI including cellular apoptosis. In this review, we summarize apoptotic molecular mechanisms involved in the etiology of EBI and its potential as a target for future therapeutic intervention.KeywoRds: Apoptosis, Early brain injury, p53, Stroke, Subarachnoid hemorrhage ÖZIntrakraniyal anevrizma rüptürüne bağlı gelişen subaraknoid kanama (SAK), yüksek mortalite ve morbidite ile seyreden kompleks bir hastalıktır. Yakın zamanda yapılan çalışmalar SAK sonrası 24-72. saatler içinde gelişen morbidite ve mortaliteden vazospasmdan ziyade, erken beyin hasarının sorunlu olduğunu ileri sürmüştür. SAK sonrasında gelişen intrakraniyal basınç artışı, serebral perfüzyon basıncında ciddi düşüşe neden olup global serebral iskemi ile sonuçlanır ve akut hasar kaskadını başlatır. Hücresel apopitoz dahil pek çok moleküler mekanizmanın erken beyin hasarının (EBH) patofizyolojisinde rol oynadığı gösterilmiştir. Bu derlemede; EBH etiyolojisinde rol alan apopitotik mekanizmalar ve bunların gelecekte potansiyel tedavi hedefi olarak önemleri özetlenmiştir.
Xenon is a medical gas capable of establishing neuroprotection, inducing anesthesia as well as serving in modern laser technology and nuclear medicine as a contrast agent. In spite of its high cost, its lack of side effects, safe cardiovascular and organoprotective profile and effective neuroprotective role after hypoxic-ischemic injury (HI) favor its applications in clinics. Xenon performs its anesthetic and neuroprotective functions through binding to glycine site of glutamatergic N-methyl-D-aspartate (NMDA) receptor competitively and blocking it. This blockage inhibits the overstimulation of NMDA receptors, thus preventing their following downstream calcium accumulating cascades. Xenon is also used in combination therapies together with hypothermia or sevoflurane. The neuroprotective effects of xenon and hypothermia cooperate synergistically whether they are applied synchronously or asynchronously. Distinguishing properties of Xenon promise for innovations in medical gas field once further studies are fulfilled and Xenon’s high cost is overcome.
Summary We report a rare case of concurrent medullary thyroid cancer (MTC) and papillary thyroid cancer (PTC) with intermixed disease in several of the lymph node (LN) metastases in a patient who was subsequently diagnosed with clear cell renal cell carcinoma (RCC). A 56 year old female presented with dysphagia and was found to have a left thyroid nodule and left superior cervical LN with suspicious sonographic features. Fine needle aspiration biopsy (FNAB) demonstrated PTC in the left thyroid nodule and MTC in the left cervical LN. Histopathology demonstrated multifocal PTC with 3/21 LNs positive for metastatic PTC. One LN in the left lateral neck dissection exhibited features of both MTC and PTC within the same node. In the right lobe, a 0.3 cm focus of MTC with extra-thyroidal extension was noted. Given persistent calcitonin elevation, a follow-up ultrasound displayed an abnormal left level 4 LN. FNAB showed features of both PTC and MTC on the cytopathology itself. The patient underwent repeat central and left radical neck dissection with 3/6 LNs positive for PTC in the central neck and 2/6 LNs positive for intermixed PTC and MTC in the left neck. There was no evidence of distant metastases on computed tomography and whole body scintigraphy, however a 1.9 x 2.5 cm enhancing mass within the right inter-polar kidney was discovered. This lesion was highly suspicious for RCC. Surgical pathology revealed a 2.5 cm clear cell RCC, Fuhrman grade 2/4, with negative surgical margins. She continues to be observed with stable imaging of her triple malignancies. Learning points: Mixed medullary-papillary thyroid neoplasm is characterized by the presence of morphological and immunohistochemical features of both medullary and papillary thyroid cancers within the same lesion. Simultaneous occurrence of these carcinomas has been previously reported, but a mixed disease within the same lymph node is an infrequent phenomenon. Prognosis of mixed medullary-papillary thyroid carcinomas is determined by the medullary component. Therefore, when PTC and MTC occur concurrently, the priority should be given to the management of MTC, which involves total thyroidectomy and central lymph node dissection. Patients with thyroid cancer, predominantly PTC, have shown higher than expected rates of RCC. To our knowledge, this is the first report describing the combination of MTC, PTC, and RCC in a single patient.
The scientific basis for the surgical management of patients with glioma is rapidly evolving. The infiltrative nature of these cancers precludes a surgical cure, but despite this, cytoreductive surgery remains central to high-quality patient’s care. In addition to tissue sampling for accurate histopathological diagnosis and molecular genetic characterisation, clinical benefit from decompression of space-occupying lesions and microsurgical cytoreduction has been reported in patients with different grades of glioma. By integrating advanced surgical techniques with molecular genetic characterisation of the disease and targeted radiotherapy and chemotherapy, it is possible to construct a programme of personalised surgical therapy throughout the patient’s journey. The goal of therapeutic packages tailored to each patient is to optimise patient safety and clinical outcome, and must be delivered in a multidisciplinary setting. Here we review the current concepts that underlie surgical management of patients with high-grade glioma.
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