Fab fragments with high affinity for ouabain and related steroids. In this respect, the isolation of an isomer of ouabain from bovine hypothalamus might be pertinent. 15 In view of the discrepant reports, it is premature to conclude that authentic ouabain is secreted by the adrenal cortex and is a functionally important circulating hormone in human beings. All we can say is that a ouabain-like compound, perhaps an isomer of ouabain, probably helps to regulate the level of arterial pressure under some circumstances-at least in laboratory animals.
Gary Nicholls, A Timothy G Yandle
M
Mark Richards,
Lynley K Lewis,
Departments of Medicine and Endocrinology, Christchurch Hospital, Christchurch, New Zealand 1
2
3
Woolfson RG, Poston L, De Wardener HE. Digoxin-like inhibitors of active sodium transport and blood pressure: the current status.
Kidney Int 1994; 46: 297-309. Ludens JH, Clark MA, DuCharme DW, et al. Purification of an endogenous digitalis-like factor from human plasma for structural analysis. Hypertension 1991; 17: 923-29. Mathews WR, DuCharme DW, Hamlyn JM, et al. Mass spectral characterization of an endogenous digitalis-like factor from human plasma. Hypertension 1991; 17: 930-35.
4
Ludens JH, Clark MA, Robinson FG, DuCharme DW. Rat adrenal cortex is a source of a circulating ouabain-like compound. Hypertension
5
Boulanger BR, Lilly MP, Hamlyn JM, Laredo J, Shurtleff D, Gann DS. Ouabain is secreted by the adrenal gland in awake dogs. Am J Physiol 1993; 264: E413-19. Laredo J, Hamilton BP, Hamlyn JM. Ouabain is secreted by bovine adrenocortical cells. Endocrinology 1994; 135: 794-97. Hamlyn JM, Manunta P. Ouabain, digitalis-like factors and hypertension. J Hypertension 1992; 10 (suppl 7): 99-111. Doris PA, Jenkins LA, Stocco DM. Is ouabain an authentic endogenous mammalian substance derived from the adrenal? Hypertension 1994; 23: 632-38. Gomez-Sanchez EP, Foecking MF, Sellers D, Blankenship MS, Gomez-Sanchez CE. Is the circulating ouabain-like compound ouabain? Am J Hypertens 1994; 7: 647-50. Lewis LK, Yandle TG, Lewis JG, et al. Ouabain is not detectable in human plasma. Hypertension 1994; 24: 549-55. Hinson JP, Dawnay AB, Raven PW. Why we should give a qualified welcome to ouabain: a whole new family of adrenal steroid hormones J Endocrinol 1995; 146: 369-72. Naruse K, Naruse M, Tanabe A, et al. Does plasma immunoreactive ouabain originate from the adrenal gland? Hypertension 1994; 23 (suppl I): 102-05. Rossi GP, Manunta P, Hamlyn JM, et al. Endogenous ouabain in primary aldosteronism (PA) and primary hypertension (PH). Seventh European Meeting on Hypertension, Milan, 1995: abstr 711. Cappuccio FP, Markandu ND, Sagnella GA, MacGregor GA. The effect of oral digoxin on sodium excretion, renin-angiotensinaldosterone system and blood pressure in normotensive subjects. Postgrad Med J 1986; 62: 265-68. Tymiak AA, Norman JA, Bolgar M, et al. Physiochemical
1992; 19: 721-24.
6 7
8
9
10 11
12
13
14
15
characterization of a ouabain isomer isolated from bovine 8189-93.
process that starts about 4-5 days after injury. Normal human mesothelial surfaces possess fibrinolytic activity but this is lost in inflammation because of cytokineinitiated production and rapid release of plasminogen activator inhibitors. 2,3 If normal fibrinolytic activity is preserved or recovers quickly, fibrous deposits are lysed and permanent adhesions are avoided. Prevention may be attempted at any stage in this pathological sequencefrom minimising injury and inflammation via anticoagulation and fibrinolytic enhancement to inhibition of fibrosis. Most adhesions follow surgical operations and are thus, in theory at least, easily amenable to attempts at prevention. However, the success of preventive methods is difficult to judge because planned second operations are unusual. Many local and systemic experimental methods of adhesion prevention are effective but few, apart from the use of talc and, more recently, starch-free gloves, have been adopted into clinical practice. Barrier methods that rely on the physical separation of surfaces with liquids, gels, or membranes have a long and varied history.’ However, recent randomised clinical trials of barrier membranes have shown striking reductions in adhesion formation after uterine adhesionolysis, pelvic and the results myomectomy, laparotomy incision, being assessed at second-look laparoscopy or laparotomy.5-7 These barriers are site-specific, allowing surgeons to control adhesion formation while avoiding the potential risks of systemic therapy. They produce minimal inflammatory response. They are either absorbable, examples being regenerated oxidised cellulose (Interceed) and hyaluronic acid (HAL-F), or permanent
clinically
[Gore-Tex (polytetrafluoroethylene Surgical Membrane]). Barriers prevent the early fibrinous gluing together of adjacent surfaces, by producing a slow-release lubricant or by providing a non-stick surface. Modification of such materials-for example, by the inclusion of anti-inflammatory, anticoagulant, or make them even more effectived fibrinolytic agents-may The time is approaching when surgeons will at last be able
Hammersmith 1
2
3
Preventing adhesions
or
at
least control, the formation of
Medical School,
Hospital, London, UK
Thompson JN, Whawell SA. Pathogenesis and prevention of adhesion formation. Br J Surg 1995; 82: 3-5. Vipond MN, Whawell SA, Thompson JN, Dudley HAF. Peritoneal fibrinolytic activity and intra-abdominal adhesions. Lancet 1990; 335: 1120-22. Whawell SA, Thompson JN. Cytokine induced release of plasminogen activator inhibitor-1 by human mesothelial cells. Eur J Surg 1995; 161: 315-17.
4
1382
prevent,
J N Thompson Department of Surgery, Royal Postgraduate
hypothalamus. Proc Natl Acad Sci (USA) 1993; 90:
Fibrous adhesions within body cavities cause substantial morbidity. They are the commonest cause of small-bowel obstruction and secondary female infertility, and represent a major hazard during cardiac reoperation. Our understanding of the pathogenesis of adhesion has improved lately.’ Injury to a mesothelial surface leads to an inflammatory response with exudation into the tissues and body cavity. Fibrin is deposited and results in fibrinous adhesions between adjacent surfaces which may then be organised into permanent fibrous adhesions, a
to
postoperative adhesions.
5
6
Wiseman D. Polymers for the prevention of surgical adhesions. Chapter 15. In: Domb AJ, ed. Polymeric site-specific pharmacotherapy. Chichester: John Wiley, 1994: 369-421. Sekiba K, and the Obstetrics & Gynaecology Adhesion Prevention Committee. Use of Interceed (TC7) absorbable adhesion barrier to reduce post-operative adhesion reformation in infertility and endometriosis surgery. Obstet Gynecol 1992; 79: 518-22. di Zerega GS. Contemporary adhesion prevention. Fertil Steril 1994; 61: 219-35.
7
Becker JM, Dayton MT, Fazio VW, et al. Sodium hyaluronate-based bioresorbable membrane (HAL-F) m the prevention of postoperative abdominal adhesions: a prospective, randomized, double-blinded multicenter study. American College of Surgeons Clinical Congress, New Orleans, October, 1995.