June 20, 2002
Use of Gene-Expression Profiles to Predict Survival after Chemotherapy for Diffuse Large-B-Cell Lymphoma
In a large group of diffuse large-B-cell lymphomas, DNA microarrays identified three patterns of gene expression that were correlated with the likelihood of survival after chemotherapy. Individual genes within these patterns formed molecular signatures that had an even stronger correlation with survival after chemotherapy. The predictive power of the molecular signatures was independent of the international prognostic index. DNA microarrays reflect the activity of tens of thousands of genes in a sample of tissue. This study of the most common lymphoma in adults focused on more than 12,000 genes expressed by lymphoid tissue and found 17 that were strongly related to the outcome. This work is an example of how microarray technology is leading to clinically useful insights into the molecular genetics of cancer.
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Abnormal Subendocardial Perfusion in Cardiac Syndrome X
Patients with cardiac syndrome X have angina and abnormal exercise-test results but normal findings on coronary angiography. Although myocardial ischemia has been suspected to be the cause, this has been difficult to document. In this study, myocardial-perfusion magnetic resonance imaging demonstrated abnormal subendocardial perfusion during adenosine infusion in 20 patients with the syndrome. Perfusion magnetic resonance imaging is a very sensitive technique for the detection of myocardial ischemia. The findings are important because they point clearly to ischemia as the cause of cardiac syndrome X and provide new insight into approaches to treatment.
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Endothelial Function and Oxidative Stress in Renovascular Hypertension
Renovascular hypertension activates the renin–angiotensin system, which can increase oxidative stress and vascular endothelial dysfunction. This study examined forearm blood flow as a marker of endothelial dysfunction before and after transluminal renal-artery angioplasty in 15 affected subjects and in 15 controls. The response of forearm blood flow to acetylcholine, an endothelium-dependent vasodilator, was diminished in subjects with renal-artery stenosis as compared with controls, and it improved after angioplasty. Responses to isosorbide dinitrate, an endothelium-independent vasodilator, were similar in all conditions in both groups. Indexes of oxidative stress such as urinary 8-hydroxy-2'-deoxyguanosine and serum malondialdehyde-modified low-density lipoprotein decreased after angioplasty. These findings suggest that increased oxidative stress is involved in impaired endothelium-dependent vasodilatation in patients with renovascular hypertension.
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Fumagillin Treatment of Intestinal Microsporidiosis
This double-blind trial involved 12 immunocompromised patients with chronic diarrhea and Enterocytozoon bieneusi infection. Treatment with fumagillin (60 mg per day orally for two weeks) led to some symptomatic improvement and to clearance of the parasite in six of six patients, as compared with none of six in the placebo group (P=0.002). All patients were eventually treated with fumagillin, but severe thrombocytopenia or neutropenia developed in three patients. There has been no effective treatment for intestinal microsporidiosis, which is a cause of chronic diarrhea, malabsorption, and wasting in severely immunocompromised patients. Fumagillin, which was once used to treat malaria, is an effective treatment against this opportunistic parasitic infection.
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Clinical Practice: Pleural Effusion
A 70-year-old man with an 80-pack-year history of smoking and a history of congestive heart failure presents with increasing shortness of breath. He also has aching chest pain on the right side that worsens with deep inspiration. He is afebrile. The chest radiograph reveals asymmetrical bilateral pleural effusions, with more fluid on the right. How should this patient be evaluated?
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Knowledge of the molecular and cellular events in heat stroke has advanced steadily during the past decade. It is now known that heat stroke is associated with injury to multiple tissues and organs as a result not only of the cytotoxic effect of heat, but also of the inflammatory and coagulation responses of the patient. Altered expression of heat-shock proteins may also have a role in the pathogenesis of heat stroke. This article reviews current understanding of the pathophysiology of heat stroke and advances in therapy.
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