Aims We compared the vasoconstrictor effects of 5-HT with those of the selective 5-HT 1B/1D -receptor agonists sumatriptan and rizatriptan in human isolated cranial (middle meningeal) arteries. In addition selective 5-HT 1B -or 5-HT 1D -receptor antibodies were used in combination with semiquantitative immunohistochemical techniques to compare the levels of expression of these receptors in human middle meningeal and coronary arteries. Methods Middle meningeal and coronary arteries were obtained (with consent) from either neurosurgical patients or donor hearts, respectively. Segments of middle meningeal artery were mounted in organ baths for isometric recording and cumulative concentration-effect curves to 5-HT, rizatriptan and sumatriptan were obtained. Frozen fresh sections of middle meningeal and coronary arteries were subjected to standard immunohistochemical techniques using specific 5-HT 1B -or 5-HT 1D -receptor primary antibodies and a radiolabelled secondary antibody. Data were subjected to analysis of variance (anova) and nonlinear regression analysis.Results 5-HT, rizatriptan and sumatriptan were potent vasoconstrictors in human isolated middle meningeal artery (EC 50 values=32, 90 and 71 nm, respectively). A significantly higher level of 5-HT 1B -receptor immunoreactivity was detected in middle meningeal artery compared with coronary artery (anova, F=7.95, DF= 1,4, P<0.05). Conclusions Rizatriptan and sumatriptan act selectively to cause vasoconstriction in human isolated middle meningeal artery and are 10-fold more potent than in human coronary artery. The higher level of expression of 5-HT 1B -receptors in middle meningeal compared with coronary artery provides a pharmacological basis for the craniovascular selectively of both rizatriptan and sumatriptan.Keywords: 5-HT 1B/1D -receptor agonists, human arteries, vasoconstriction importance since this may lead to coronary adverse events Introduction [12, 13]. It has been reported that 5-HT 1B -receptors mediate vasoconstriction in cranial/cerebral arteries and also in It is generally accepted that migraine headache is accompanied by excessive vasodilation of extracerebral, coronary arteries [4][5][6]. However, sumatriptan acts selectively in cranial arteries compared with coronary arteries since the intracranial blood vessels and that the therapeutic action of 5-HT 1B/1D -receptor agonists such as sumatriptan can result, incidence of cardiac adverse-events related to sumatriptan administration in migraineurs is rare. at least in part, from cranial vasoconstriction [1-3] via activation of vascular 5-HT 1B -receptors [4][5][6][7]. (Note in this Previously we have reported two independent coronary artery studies (using different experimental protocols) where report we follow the recently adopted nomenclature of 5-HT 1B -and 5-HT 1D -receptors, however, these subtypes the maximum contraction evoked by the selective 5-HT 1B/1D -receptor agonist rizatriptan was found to be signifiare also known in the literature as 5-HT 1Db and 5-HT 1Da receptors, respectivel...
There may be considerable difficulty in making a definitive diagnosis in colitis from histopathology alone. This study is based on a well-tried system which has been used for 15 years in the University Hospital of South Manchester for the reporting of colonic biopsies. The varieties of histopathological pattern seen in colitis are described and the study shows how they can be used to refine diagnosis when good communication is maintained between the clinician and the histopathologist. The histopathology report is based on describing histological patterns rather than diagnoses but includes a differential diagnosis. The pathology report will allow the clinician together with the known clinical information to make an appropriate management decision. Ideally the final diagnosis is reached at a clinico-pathological conference.
There has been a significant increase of litigation in the UK in recent years and for this reason it is appropriate to analyse the reasons for civil litigation. Alleged medical negligence in the colorectal field comes from the activity of general surgeons and gynaecologists as well as colorectal surgeons. This communication deals with problems in the coloproctology area irrespective of the surgeon involved. Two hundred and forty-five cases are reviewed, consisting of 49 anal problems, 160 abdominal problems with 24 laparoscopic and 12 colonoscopic injuries. Thirty-two of 49 anal cases had incontinence and these were often difficult to defend, especially the 20 cases due to childbirth injury because of poor documentation. The abdominal problems were due to delay or complications of surgery. The cases based on delay in diagnosis of cancer were often unsuccessful, but the cases of delay in diagnosis of intra-abdominal infection were difficult to defend. Problems occurring in the operative or early post-operative period produced allegations which were often justified, but the late complications of surgery were rarely due to poor standard of care. The laparoscopic injuries included bowel perforation, bleeding and major vascular damage which were not recognized at the time. The colonoscopic cases were chiefly due to perforation, which is easily defended provided the endoscopist is experienced and the risk is recorded in the consent. The cases have yielded a number of lessons which are discussed and compared with the American experience. It is concluded that litigation is traumatic to both plaintiff and surgeon and that better ways should be found to resolve complaints of inadequate care.
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