The development and neoplastic progression of human astrocytic tumors appears to result through an accumulation of genetic alterations occurring in a relatively defined order. One such alteration is amplification of the epidermal growth factor receptor (EGFR) gene. This episomal amplification occurs in 40-50% of glioblastomas, which also normally express endogenous receptors. Moreover, a significant fraction of amplified genes are rearranged to speifically eliminate a DNA fragment containing exons 2-7 of the gene, resulting in an in-frame deletion of 801 bp of the coding sequence of the extracellular domain. Here we used retroviral transfer of such a mutant receptor (de 2-7 EGFR) into glioblastoma cells expressing normal endogenous receptors to test whether the mutant receptor was able to augment their growth and malignancy. Western blotting analysis showed that these cells expressed endogenous EGFR of 170 kDa as well as the exogenous de 2-7 EGFR of 140-155 kDa. Although holoEGFRs were phosphorylated on tyrosine residues only after exposure of the cells to liand, de 2-7 EGFRs were constitutively phosphorylated. In tissue culture neither addition ofEGF nor expression of the mutant EGFR affected the rate of cell growth. However, when cells expressing mutant EGFR were implanted into nude mice subcutaneously or intracerebrally, tumorigenic capacity was greatly enhanced. These results suggest that a tumor-specific alteration of the EGFR plays a significant role in tumor progression perhaps by influencing interactions oftumor cells with their microenvironment in ways not easily assayed in vitro.

Nonalcoholic fatty liver disease (NAFLD) describes a range of disorders characterized by excess accumulation of triglyceride within the liver. While simple steatosis may be clinically stable, nonalcoholic steatohepatitis (NASH) can be progressive. Inflammation is believed to be the driving force behind NASH and the progression to fibrosis and subsequent cirrhosis. This article will review and interpret the current literature in an attempt to expand our understanding of the environmental and genetic causes of inflammation and its effects in NAFLD.

The high-risk patient for readmission is a woman with diabetes, chronic lung disease, renal insufficiency, and preoperative atrial fibrillation who lives at a distance from the hospital. Readmission does not depend on periprocedural variables (eg, cardiopulmonary bypass time) or on postoperative complications. High procedural costs from the initial hospitalization do not predispose to readmission. These results suggest interventions that may reduce readmission.

Dyspepsia is a common clinical problem seen by both primary care physicians and gastroenterologists. Initial evaluation should focus on the identification and treatment of potential causes of symptoms such as gastroesophageal reflux disease (GERD), peptic ulcer disease, and medication side effects but also on recognizing those at risk for more serious conditions such as gastric cancer. This manuscript discusses the evaluation and management of dyspepsia including the role of proton-pump inhibitors, treatment of Helicobacter pylori, and endoscopy. Finally, treatment of refractory functional dyspepsia is addressed.