The no-reflow phenomenon: epidemiology, pathophysiology, and therapeutic approach.

Over the past 20 years, advances in the management of ST segment elevation myocardial infarction have focused on the rapid achievement of patency in the infarct-related artery. The limitation of this therapeutic strategy has been exposed with the development of diagnostic techniques to assess coronary microcirculation, including myocardial contrast echo, magnetic resonance imaging, myocardial perfusion grading, and the coronary flow wire. These methods have expanded our ability to understand and recognize the no-reflow phenomenon, which describes the absence of tissue perfusion despite epicardial coronary artery patency and flow. Although the mechanisms responsible for the development of no reflow are not fully understood, the end result is microvascular damage produced by microvascular obstruction or reperfusion injury. Ideally, early recognition of the no-reflow phenomenon should provide an opportunity for therapeutic intervention designed to augment tissue perfusion and maintain the viability of myocardium at risk. A number of pharmacologic agents are being used in conjunction with percutaneous transluminal coronary angioplasty in an attempt to improve microvascular perfusion. These include IIb/IIIa receptor antagonists, adenosine, verapamil, and the experimental agent nicorandil. In the new millennium, the emphasis of reperfusion therapy is being shifted downstream from its exclusive focus on the epicardial artery to assuring normal blood flow at the tissue level. This article will review the epidemiology, pathophysiology, and therapeutic approach to this vexing clinical problem.

Ancient medicine: the patient's perspective.

A number of previously unpublished therapeutic recipes from cuneiform tablets in Berlin (Pergamon Museum) and London (British Museum) list symptoms describing urinary tract disfunction. In addition to presenting extracts from this material, the present article discusses the roles of physician as apothecary or exorcist in ancient texts from Babylonia. This involves technical medical knowledge vs. ""bed-side manner"", taking into account the psychological effects of drug therapy and diagnosis.

Arachidonic and linoleic acid metabolism in mouse intestinal tissue: evidence for novel lipoxygenase activity.

Previous studies in our laboratory revealed a high expression of 15-lipoxygenase-1 in human colorectal carcinomas, suggesting the importance of lipoxygenase in colorectal tumor development. In this report, we have investigated the metabolism of arachidonic and linoleic acid by intestinal tissues of Min mice, an animal model for intestinal neoplasia. The polyp and normal tissues from Min mice intestine were homogenized, incubated with arachidonic or linoleic acid, and analyzed by reverse-, straight-, and chiral-phase HPLC. Arachidonic acid was converted to prostaglandins E2 and F2alpha. Little 12- or 15-hydroxyeicosatetraenoic acid was detected. Cyclooxygenase (COX)-2 was detected in polyps and the adjacent normal tissues by Western immunoblotting, but neither COX-1 nor leukocyte-type 12-lipoxygenase, the murine ortholog to human 15-lipoxygenase-1, was detected. These tissue homogenates converted linoleic acid to an equal mixture of 9(S)- and 13(S)-hydroxyoctadecadienoic acid (HODE). Inhibition of lipoxygenase activity with nordihydroguaiaretic acid blocked HODEs formation, but the COX inhibitor indomethacin did not. Degenerative-nested PCR analyses using primers encoded by highly conserved sequences in lipoxygenases detected 5-lipoxygenase, leukocyte-type 12-lipoxygenase, platelet-type 12-lipoxygenase, 8-lipoxygenase, and epidermis-type lipoxygenase-3 in mouse intestinal tissue. All of these PCR products represent known lipoxygenase that are not reported to utilize linoleic acid preferentially as substrate and do not metabolize linoleic acid to an equal mixture of 9(S)- and 13(S)-HODE. This somewhat unique profile of linoleate product formation in Min mice intestinal tissue suggests the presence of an uncharacterized and potentially novel lipoxygenase(s) that may play a role in intestinal epithelial cell differentiation and tumor development.