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T P Crotty

Publications and source records attributed to T P Crotty.

14 recordsLinked to original sources
PubMed1999

Efficacy of bilateral prophylactic mastectomy in women with a family history of breast cancer.

BACKGROUND: Options for women at high risk for breast cancer include surveillance, chemoprevention, and prophylactic mastectomy. The data on the outcomes for surveillance and prophylactic mastectomy are incomplete. METHODS: We conducted a retrospective study of all women with a family history of breast cancer who underwent bilateral prophylactic mastectomy at the Mayo Clinic between 1960 and 1993. The women were divided into two groups - high risk and moderate risk - on the basis of family history. A control study of the sisters of the high-risk probands and the Gail model were used to predict the number of breast cancers expected in these two groups in the absence of prophylactic mastectomy. RESULTS: We identified 639 women with a family history of breast cancer who had undergone bilateral prophylactic mastectomy: 214 at high risk and 425 at moderate risk. The median length of follow-up was 14 years. The median age at prophylactic mastectomy was 42 years. According to the Gall model, 37.4 breast cancers were expected in the moderate-risk group; 4 breast cancers occurred (reduction in risk, 89.5 percent; P<0.001). We compared the numbers of breast cancers among the 214 high-risk probands with the numbers among their 403 sisters who had not undergone prophylactic mastectomy. Of these sisters, 38.7 percent (156) had been given a diagnosis of breast cancer (115 cases were diagnosed before the respective proband's prophylactic mastectomy, 38 were diagnosed afterward, and the time of the diagnosis was unknown in 3 cases). By contrast, breast cancer was diagnosed in 1.4 percent (3 of 214) of the probands. Thus, prophylactic mastectomy was associated with a reduction in the incidence of breast cancer of at least 90 percent. CONCLUSIONS: In women with a high risk of breast cancer on the basis of family history, prophylactic mastectomy can significantly reduce the incidence of breast cancer.

Adolescent↗
PubMed1999

Contraction in the smooth muscle cell.

This paper advances the hypothesis that the rearrangement of the actin cytoskeleton that takes place during contraction in the SMC is a mechanical reflection of the spatiotemporal pattern of the cell's polarized stimulus. In that sense the cell is responding more like a motile non-muscle cell than like a skeletal muscle cell. The paper reviews how diffusion patterns are generated and modified and suggests how the patterns are detected by the cell and transduced into cytoskeletal movement. Evidence is presented suggesting the actin cytoskeleton is composed of conical-shaped myofibrils (contractile units) measuring half a cell in length and containing filament-free spaces at their centres filled with cell inclusions. It is argued that the SMC contracts by involving variable combinations of the myofibrils in sequence and that the cell takes advantage of that fact to translocate various contractile elements between the myofibrils during contraction, thus economizing on its needs for those elements. Among the elements translocated are thought to be myosin, SR and mitochondria.

Actins↗
PubMed1996

The role of radial reflux in the genesis of varicose veins.

The first section of this paper reviews the clinical, histochemical and histological features of the varicosity in the early stage of human varicose veins. The second section demonstrates that many of those features have been duplicated in acute experiments where noradrenaline perfused the vasa venarum of an isolated in situ canine vein segment, the drug having reached the vasa by reflux from the lumen of the segment (radial reflux). It also explains how perfusion of the vasa for an extended period would duplicate other distinctive features of the early-stage human varicosity, such as its permanence, the hypoxia of its tissues and the hypertrophy of the smooth muscle in its wall. The findings further support the hypothesis that varicose veins arise from chronic perfusion of the vasa venarum of a normal vein by circulating noradrenaline contained in pathologically high volumes of radial venous reflux. The main cause of the high volume of reflux seems to be turbulent luminal flow in the case of secondary varicose veins and a real or relative structural deficiency of the fibroelastic of the valve aggers in the case of primary ones.

Animals↗
PubMed1994

Poststenotic dilatation in arteries and the role of turbulence.

A hypothesis is presented on the origin of PSD, the dilatation which occurs in an artery distal to a site of stenosis. The fact that turbulent flow is associated with both PSD and with experimentally induced varicosities suggested that similar mechanisms are involved. That is the basis for a proposal that PSD originates as an active dilator response of the artery wall to circulating NE released in excess from a section of the vasa vasorum (VV) network of the affected artery. Turbulence is believe to be the cause of that excess through multiplying the volume of blood and, consequently, the amount of circulating NE flowing from an artery to its VV. There is published evidence that turbulence does increase flow to the VV of an artery and evidence is presented that if norepinephrine is injected rapidly into a small canine muscular artery, with the aim of creating turbulence in the artery, the injection is promptly followed by localised dilator effects in the artery which, overall, is constricted by the drug.

Animals↗
PubMed1992

The vasa vasorum and the paradox of beta-blocker therapy.

The use of beta-blockers in the treatment of angina, claudication or hypertension is a therapeutic paradox. All those conditions feature increased constrictor tone, so it appears to make little sense to treat them with drugs which block the action of vasodilators. The paradox would disappear, however, if vasodilators could be shown to have the ability to increase constrictor tone in certain circumstances. This paper argues that they have. It presents evidence that isoprenaline, a potent dilator of the dog's saphenous vein, is a powerful constrictor of the vein when it is released from the vasa vasorum of the vein. Indeed, on a molar basis, it appears to be a more powerful constrictor of the vein than exogenous noradrenaline is. Since there is no reason to suppose that isoprenaline is unique among dilators in demonstrating this type of bimodal behaviour, it is possible to justify the proposal that compounds which are normally classified as endogenous dilators may, when released from the pathological vasa vasorum which neoproliferate in atherosclerosis, be responsible for the constrictor effects associated with claudication, and some forms of hypertension and angina. If true then beta-blockade would not be a paradoxical choice of treatment for those conditions.

Adrenergic beta-Antagonists↗
PubMed1992

The origin and the progression of varicose veins.

It is proposed that pathological varicosities begin as acute dilator responses of normal veins to noradrenaline released from the vasa vasorum of the vein; the noradrenaline is part of a circulating pool formed by overflow following adrenergic nerve activity. In health, a minimal quantity of noradrenaline routinely flows by reflux to the vasa where it has a negative feedback, venodilator effect. However, when the volume of reflux becomes excessive, the noradrenaline in it abolishes venoconstrictor tone, thereby creating a varicosity. Excessive venous reflux over a short period causes no significant hypoxic damage to the vein wall or any other tissues and any damage associated with it regresses when the excess reflux ceases. However, if excessive reflux is persistent then a time comes when irreversible hypoxic structural changes occur in the vein wall and in other tissues affected by the reflux. The structural pathology associated with varicose veins reflects the effect of the long-term tissue hypoxia associated with that condition.

Animals↗
PubMed1991

The roles of turbulence and vasa vasorum in the aetiology of varicose veins.

Noradrenaline can dilate a canine lateral saphenous vein which at the time is constricted by noradrenaline. It does so when it is released from the vasa vasorum network of the constricted vein. By filling a limited section of the network of a normal, tonically constricted vein with endogenous noradrenaline it is possible to dilate the vein locally, in effect creating an acute experimental varicosity. These findings have led to the proposal that human varicosities are an active response of the vein to endogenous noradrenaline released from sections of its vasa vasorum network. The noradrenaline involved is part of the circulating overflow derived from normal adrenergic nerve activity. A bout of turbulence in the vein lumen is proposed as the trigger which causes a reflux of hypoxic blood and the endogenous noradrenaline in it from the vein lumen to the vasa. The size and shape of the varix reflects the mosaic pattern of a vein's vasa vasorum network. The site of the varicosity is determined by the location in the vein lumen of the bout of turbulent non-laminar flow.

Animals↗
PubMed1991

Is circulating noradrenaline the cause of varicose veins?

When noradrenaline, either endogenous or exogenous, is released from the venae venarum of a dog's lateral saphenous vein which is constricted by noradrenaline, it dilates the vein. By limiting the release of the drug to just a section of the vein's venae venarum network it is possible to dilate the normal vein segmentally, that is, cause varicosities. This has led to the suggestion that pathological varicosities begin as localised physiological dilator responses of the vein wall to circulating endogenous noradrenaline, released from the vein's venae venarum. Under ambulatory conditions small quantities of noradrenaline probably flow almost continually from the lumen of the vein to different parts of its venae venarum network and serve to adjust constrictor tone downwards. When there is turbulence in the vein lumen the volume of reflux becomes excessive and causes so much adjustment that constrictor tone is abolished. The vein, in effect, then exhibits a frank dilator effect, visible as a varicosity, localised to the level in the vein at which the turbulence occurs. If a high volume of hypoxic blood reflux continues for a critical period then the wall of the varicosity suffers secondary degenerative structural changes which make the varicosity permanent.

Animals↗
PubMed1989

The role of vasa vasorum in atherosclerosis.

Experiments have shown that noradrenaline can dilate the lateral saphenous vein of the dog when that vein has been constricted by noradrenaline, at the same concentration, in the first place. This dilator action of noradrenaline occurs when the drug stimulates the constricted vein through its outer surface after it is released from the vein's vasa vasorum network. There is evidence suggesting that this effect is not unique to noradrenaline and that the effect of any agonist stimulating a blood vessel through its lumenal surface may be reversed following its release from vasa vasorum. This phenomenon may be important in the context of the known relationship there is between the severity of the symptoms of atherosclerosis and the degree to which vasa vasorum proliferate de novo in the adventitia of blood vessels affected by that disease. It is suggested that in atherosclerosis endogenous vasodilators have their actions reversed by release from these pathological vasa. This would result in the vasodilators of exercise having a constrictor action on the coronary vessels and becoming the immediate cause of angina. If vasodilators do indeed cause angina then the use of beta-blockade in this condition becomes a rational rather than an empirical method of treatment. An hypothesis is advanced to explain the phenomenon of drug action reversal.

Animals↗
PubMedDate not supplied

The corrupted feedback hypothesis.

This paper argues that varicose veins are caused by a feedback malfunction. The feedback in question regulates the tone of the vein by dilating it as needed, using noradrenaline (NA), tapped from the circulating pool, for the purpose. The drug, though conventionally classified as a venoconstrictor, dilates the vein when it diffuses from the vasa venarum of the vein into the vein's media; the drug having reached the vasa by reflux from the vein lumen. A varicosity is created when a factor increases the volume of reflux, and, therefore, the quantity of NA, perfusing a unit of the vasa network, selectively. The resultant, exaggerated, localised, dilator effect that the NA has on a section of the vein, constitutes the varicosity radix. In brief, a varicosity, when first created, is seen as being an exaggerated, but appropriate, dilator response of a section of a normal vein to an inappropriate, corrupted, feedback signal. The acute varicosity is believed to transform into the permanent type seen in varicose veins if the factor responsible for it persists long enough.

Endothelium, Vascular↗