Human melanoma cells growth arrest irreversibly, lose tumorigenic potential and terminally di erentiate after treatment with a combination of ®broblast interferon (IFN-b) and the protein kinase C activator mezerein (MEZ). Applying subtraction hybridization to this model di erentiation system permitted cloning of melanoma di erentiation associated gene-7, mda-7. Expression of mda-7 inversely correlates with melanoma development and progression, with elevated expression in normal melanocytes and nevi and increasingly reduced expression in radial growth phase, vertical growth phase and metastatic melanoma. When expressed by means of a replication incompetent adenovirus (Ad.mda-7) growth of melanoma, but not normal early passage or immortal human melanocytes, is dramatically suppressed and cells undergo programmed cell death (apoptosis). Infection of metastatic melanoma cells with Ad.mda-7 results in an increase in cells in the G 2 /M phase of the cell cycle and changes in the ratio of pro-apoptotic (BAX, BAK) to anti-apoptotic (BCL-2, BCL-XL) proteins. Ad.mda-7 infection results in a temporal increase in mda-7 mRNA and intracellular MDA-7 protein in most of the melanocyte/melanoma cell lines and secretion of MDA-7 protein is readily detected following Ad.mda-7 infection of both melanocytes and melanoma cells. The present studies document a di erential response of melanocytes versus melanoma cells to ectopic expression of mda-7 and support future applications of mda-7 for the genebased therapy of metastatic melanoma.

DescriptionA 5-year old girl with congenital mitral and subaortic stenosis on anticoagulant therapy since her mechanical mitral valve replacement, and a remote history of idiopathic intrahepatic cholestasis requiring liver transplantation presented with jaundice and pruritus. She was found to have elevated transaminases, and an echocardiogram revealed significantly increased right ventricular pressures concerning for pulmonary hypertension. Subsequently, the patient needed to be intubated for respiratory insufficiency and poor cardiac output. After several days in the intensive care unit (ICU), she was noted to be bradycardic and have a dilated right pupil. A stat CT of the head demonstrated a large mixed density right-sided subdural haematoma with mass effect, midline shift and early uncal and transtentorial herniation, as well as a small subdural haematoma on the left (figure 1). The mixed density of the haematoma on CT scan was likely a result of multiple haemorrhages over the previous several days and/or hyperacute blood product accumulation in the setting of a coagulopathy.The patient was taken to the operating room for emergent decompressive craniectomy and evacuation of subdural haematoma. Prior to surgery, her coagulopathy was reversed with protamine, decreasing her PTT from 150 to 37 s. The patient was also given mannitol and hyperventilated as temporising measures while the operating room was being prepared. A large right frontotempoparietal craniectomy was performed in standard fashion. Removal of the bone flap revealed impressive swelling and tense dura with a blue tint. The dura was then opened progressively to avoid herniation of brain tissue or hypotension. Extensive mixed density clot was evacuated to reveal markedly swollen brain parenchyma with a mottled appearance, likely due to a combination of cerebral contusions from the mass effect of the haematoma as well as the patient's underlying venous hypertension (figure 1). After a satisfactory and uneventful decompression, an ICP monitor was placed, the bone flap was left off and the skin was closed in routine fashion. The patient was kept intubated and transported back to the ICU for further management. Figure 1 CT of the head showing right-sided subdural haematoma with mass effect, midline shift and a small subdural haematoma on the left and swollen brain parenchyma with mottled appearance after evacuation of subdural haematoma and decompressive craniectomy. Learning points

Williams-Beuren syndrome, also known as Williams syndrome (WS) is a genetic disorder involving the elastin gene on chromosome 7q11.23. Elastin is important for elasticity of vascular walls, and its deficiency can lead to widespread arteriopathy, most notably supravalvar aortic stenosis of the ascending aorta and coronary artery stenosis. Because of these cardiac defects, patients with WS are at high risk for cardiac arrest under anesthesia with a documented incidence around 5%. Appropriate perioperative management of all anesthetics includes a multidisciplinary approach to risk stratification, precise anesthetic management, and disaster planning. This chapter reviews the etiology, pathogenesis, diagnosis, and manifestations of WS. The authors also discuss the preoperative workup and anesthetic implications of WS, as well as issues related to cardiac arrest and extracorporeal cardiopulmonary resuscitation.