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March 13, 2008  Vol. 358 No. 11

Audio Summary of this Issue

Perspective
1089-1092
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Africa is facing the worst tuberculosis epidemic since the advent of the antibiotic era. Drs. Richard Chaisson and Neil Martinson write that the unprecedented growth of the epidemic is attributable to several factors, the most important being the HIV ...

1092-1095

Dr. Vikram Paralkar writes that many people with tuberculosis in India continue to slip through the net and into jostling crowds, with at most a thin handkerchief to stifle their incessant coughs.

Original Articles
1097-1108
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Anesthesia awareness has potential psychological consequences. Use of the bispectral index (BIS) developed from a processed electroencephalogram has been reported to decrease anesthesia awareness. In this randomized, controlled trial comparing a BIS-based protocol with a protocol based on measurement of end-tidal anesthetic gases, two cases of definite anesthesia awareness occurred in each group. This study did not show a benefit of BIS monitoring in reducing the rate of anesthesia awareness.

1109-1117

Immediate hypersensitivity reactions to the monoclonal antibody cetuximab, used for the treatment of colorectal cancer and cancer of the head and neck, were found to be associated with IgE antibodies against cetuximab. These antibodies were present in pretreatment serum and were specific for galactose-α-1,3-galactose on the heavy chain of the cetuximab monoclonal antibody.

1118-1128

Methylation of the promoter region of a gene is a mechanism that influences gene expression. In this study of patients with stage I non–small-cell lung cancer (NSCLC), methylation of seven genes — p16, CDH13, APC, RASSF1A, MGMT, ASC, and DAPK — from tumor and lymph-node specimens was studied. Four genes (p16, CDH13, RASSF1A, and APC), when methylated, were associated with recurrence after surgery with curative intent.

1129-1136

In six patients who received bevacizumab, a humanized monoclonal antibody against vascular endothelial growth factor (VEGF), proteinuria subsequently developed, and thrombotic microangiopathy was shown on renal biopsy. In a murine model, the authors showed that using conditional gene targeting to ablate the VEGF gene from renal podocytes can trigger thrombotic microangiopathy. This finding suggests that glomerular injury from bevacizumab may be due to the direct targeting of VEGF.

Special Article
1137-1147

In this large case–control study in India, the prevalence of smoking was about 5% among women and 37% among men between the ages of 30 and 69 years. Smoking was associated with increased mortality from tuberculosis, respiratory disease, cardiovascular disease, and cancer.

Review Articles
1148-1159

Gene transcription can be activated or inhibited by a reversible modification of the gene; this modification is termed an epigenetic change. This account of epigenetics in cancer reviews the mechanisms and consequences of epigenetic changes in cancer cells and concludes with the implications of these changes for the diagnosis, prognosis, and treatment of cancer.

1160-1174

Functional activation of growth factors and receptors of the epidermal growth factor receptor (EGFR) family occurs in most epithelial-cell cancers, rendering EGFR a target for cancer treatment. This article discusses the mechanisms of action of EGFR inhibitors, their anticancer activity, and clinical issues concerning their use in the treatment of patients with cancer.

Images in Clinical Medicine
1175
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A 55-year-old woman with metastatic lung cancer was treated with erlotinib, a tyrosine kinase inhibitor of the epidermal growth factor receptor. Cutaneous toxic effects are specific to this class of agents and are associated with an improved clinical ...

e12
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This 76-year-old man with a kidney transplant underwent radical surgery for esophageal carcinoma. He received methylene blue through his nasogastric tube to look for a possible fistula.

Case Records of the Massachusetts General Hospital
1176-1187

A 33-year-old man was admitted to the hospital with fever, abdominal pain, and pancytopenia 15 years after renal transplantation. Imaging studies disclosed hepatosplenomegaly. A diagnostic procedure was performed.

Editorial
1189-1191

More than 21 million patients in North America alone receive general anesthesia each year,1 and thanks to increasing knowledge, skill, and sophisticated technology, the vast majority of anesthetic procedures are uneventful. However, a rare but serious ...

Clinical Implications of Basic Research
1192-1193

Experiments using a mouse model of type 1 diabetes indicate that immunosuppressants used in islet transplantation may suppress beta-cell proliferation.

Correspondence
1194-1195

To the Editor: Poeta et al. (Dec. 20 issue)1 report that a disruptive alteration of the gene for the tumor-suppressor protein p53 (TP53), as compared with the absence of a TP53 mutation, had an independent, significant association with decreased survival ...

1195-1197

To the Editor: The study by Jonker et al. (Nov. 15 issue)1 showed that cetuximab improved survival among patients with colorectal cancer, but the authors give no details regarding sites of metastases in the cetuximab group. Were metastatic sites in ...

1197-1198

To the Editor: Holman et al. (Oct. 25 issue)1 report on the Treating to Target in Type 2 Diabetes (4-T) study of the addition of insulin to oral therapy in patients with type 2 diabetes. I think it is unreasonable for the authors to conclude that better ...

1199-1200

To the Editor: Wang et al. (Nov. 22 issue)1 provide a well-reasoned assessment of the statistical issues related to subgroup analyses. However, one important point that should be made is that significance testing during subgroup analyses is seldom ...

1200-1201

In a woman with MRSA, recurrent deep abscesses resolved only after treatment of the family's MRSA-positive cat.

Book Reviews
1202-1203

Seen from the air, Ellis Island resembles a letter U anchored in the Hudson River. The right arm of the U contains the Great Hall — the iconic building where prospective immigrants were screened. In most cases, they were able to leave the island for ...

1203-1204

Priscilla Wald, a professor of English at Duke University, was motivated to write Contagious by her “conviction that an analysis of how the conventions of the outbreak narrative shape attitudes toward disease emergence and social transformation can lead ...

1204

In this fascinating overview of the history of plastic surgery, the text is set out clearly and methodically with numerous impressive color illustrations. The book gives ample evidence that plastic surgery is one of the oldest surgical specialties, with ...

Correction
1204

A New Arenavirus in a Cluster of Fatal Transplant-Associated Diseases (published Online First at www.nejm.org on February 6, 2008, DOI: 10.1056/NEJMoa073785) Original Article, N Engl J Med 2008:358;991-998.. In the Abstract, the first sentence under ...