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Biomedical subjects

W G Haynes

Publications and source records attributed to W G Haynes.

83 records · Page 5Linked to original sources
PubMed1992

The potassium channel opener BRL 38227 inhibits binding of [125I]-labelled endothelin-1 to rat cardiac membranes.

Binding of [125I]-labelled endothelin-1 (ET-1) to rat cardiac membranes and the effects of endothelin-1 (ET-1), endothelin-3 (ET-3), the calcium channel antagonist nifedipine, and both enantiomers of the potassium channel opener cromakalim (BRL 34915) on binding have been examined. Specific binding of [125I]-ET-1 was inhibited in a concentration dependent manner by both unlabelled ET-1 (10(-12)-10(-7) M) and ET-3 (10(-12)-10(-6) M). Nifedipine (10(-11)-10(-5) M) did not affect [125I]-ET-1 binding. However, BRL 38227 (10(-11)-10(-5) M), the biologically active isomer of cromakalim, significantly inhibited [125I]-ET-1 binding. The inactive isomer, BRL 38226 (10(-11)-10(-5) M) had no effect. These findings provide the first evidence for a stereospecific interaction between BRL 38227 and an ET-1 binding site in rat cardiac membranes.

Animals↗
PubMed1991

Pharmacology of endothelin-1 in vivo in humans.

Endothelin-1 (ET-1) is a potent vasoconstrictor and pressor agent with a prolonged action in animal preparations. We have investigated the vascular pharmacology of ET-1 in healthy human volunteers. In arterial studies, blood flow was measured in both forearms and the left brachial artery cannulated for infusion of drugs and vehicle. Local blood flow was reduced in a dose-dependent manner by ET-1. At 5 pmol/min, the response was maximal by 60 min, and flow returned to baseline only after a further 120 min. ET-1 and angiotensin II, both at 5 pmol/min, reduced flow by 40% at 60 min. These responses were reversed to a similar degree by the dihydropyridine calcium antagonist nicardipine (0.3-10 micrograms/min). At 1 pmol/min, ET-1 did not affect sympathetic vasoconstriction to arterial norepinephrine or lower body negative pressure. In venous studies, the internal diameter of a dorsal hand vein was measured during local infusion of drugs and vehicle. ET-1 (5 pmol/min) produced local venoconstriction, with a maximal reduction in vein size of 83 +/- 12% at 60 min. Reversal of responses was slow, and unaffected by nicardipine (1.5 micrograms/min). We have shown that ET-1 is a potent vasconstrictor producing prolonged effects in resistance and capacitance vessels in humans. Low-dose ET-1 does not appear to affect sympathetically mediated vasoconstriction. Studies with nicardipine do not provide support for the hypothesis that ET-1 is an endogenous ligand of the dihydropyridine-sensitive calcium channel.

Adult↗
PubMed1988

Anorectal contractility under basal conditions and during rectal infusion of saline in ulcerative colitis.

Pressure activity in the rectum and anal canal was measured with a multilumen probe in 29 patients with ulcerative colitis (12 active, 11 quiescent, six studied during both phases) and 18 normal controls under resting conditions and during rectal infusion of saline. Resting motor activity was significantly decreased in patients with active colitis compared with quiescent colitis (p less than 0.005) and normal controls (p less than 0.001). Forty per cent of active colitics showed a featureless record compared with only one patient with quiescent colitis and one normal subject. The volume of saline infused before leakage occurred, and the total volume retained were significantly lower (p less than 0.001) in patients with active and quiescent colitis compared with normal controls. Rectal infusion of saline provoked regular rectal contractions, of significantly higher (p less than 0.05) amplitude in patients with active colitis, than in quiescent colitis or controls. These rectal contractions were associated with simultaneous anal relaxations. During saline infusion, peak and pressures were lower in patients with ulcerative colitis than in normal subjects, but there were no significant differences in relaxation pressures. In normal subjects, the rectal pressures remained below the anal pressures throughout the saline infusion. Peak rectal pressures exceeded the anal relaxation pressures during the last five minutes of saline infusion in patients with ulcerative colitis and throughout the infusion in those patients who complained of incontinence. Results suggest that although the resting rectal motor activity is diminished in patients with ulcerative colitis, luminal distension causes the inflamed rectum to generate abnormally strong contractions that may threaten continence.

Adult↗
PubMed1983

Differences in anorectal manometry between patients with haemorrhoids and patients with descending perineum syndrome: implications for management.

Anorectal manometry was carried out at rest, during balloon distension of the rectum and during rectal infusion of saline in 19 patients with haemorrhoids, 30 patients with descending perineum syndrome and 21 controls. Basal and squeeze pressures were significantly higher in patients with haemorrhoids than patients with the descending perineum syndrome. A lower rectal volume was required to inhibit internal sphincter tone in patients with descending perineum syndrome compared with control subjects or patients with haemorrhoids. During rectal infusion of saline basal and peak anal pressures in patients with the descending perineum syndrome were lower than in haemorrhoid patients. Peak rectal pressure was abnormally high in both groups. These differences in anorectal function suggest that despite a similar presentation, the two conditions have a different pathogenesis. Moreover, inappropriate anal sphincter stretch or mucosal excision in patients with descending perineum syndrome may lead to severe incontinence.

Anal Canal↗
PubMed1983

Use of anorectal manometry during rectal infusion of saline to investigate sphincter function in incontinent patients.

Anal and rectal pressures and external sphincter electromyogram were recorded continuously during rectal infusion of 1.5 L saline in 18 normal subjects and 37 patients who complained of diarrhea and fecal incontinence. All subjects exhibited a pattern of regular fluctuations in anorectal pressure and electromyogram. All except 1 of the normal subjects were able to retain 1500 ml saline without leakage, and their pressure record comprised simultaneous rectal contractions, internal sphincter relaxations, and external sphincter contractions. None of the incontinent patients were able to retain 1500 ml saline without leakages, and leakages always coincided with the peaks of rectal pressure. Two manometric patterns were observed. Fifty-nine percent of incontinent patients exhibited a pattern of contractions of similar profile occurring throughout the anorectum. This finding was associated with low basal sphincter pressures, an easily inhibited anal sphincter tone, an obtuse anorectal angle, and a funnel-shaped configuration to the anal canal. These results suggested that, in this group, the internal sphincter was weak and easily inhibited so that the whole anorectum behaved as one fluid-filled compartment recording contractions of the external sphincter. The remaining 41% of incontinent patients exhibited a normal pattern of anorectal pressure fluctuations and had normal maximum basal pressures, although maximum squeeze pressures, rectoanal inhibitory reflex, and anorectal angles were abnormal. Peak rectal pressures were abnormally high in this group during saline infusion, suggesting that abnormally strong rectal contractions may play a role in the incontinence in this group.

Adult↗
PubMed1982

A prospective study of the effect of haemorrhoidectomy on sphincter function and faecal continence.

The effect of haemorrhoidectomy on anal sphincter manometry and continence to faeces and rectally infused saline was investigated in 24 unselected patients with third-degree haemorrhoids. Haemorrhoidectomy resulted in the abolition of ultra-slow waves and significant decreases in basal and squeeze pressures, though these were reduced to normal values from abnormally high levels. Pressures remained at normal levels up to a year after surgery. An association was found between mucous soiling following surgery and an abnormally low postoperative squeeze pressure. There was no alteration in the function of the recto-anal inhibitory reflex following surgery. Only two patients developed incontinence to rectally infused saline for the first time following surgery. The addition of four-finger dilatation of the anal canal to the operative procedure did not cause any significant differences in sphincter manometry.

Adult↗
PubMed1982

Ano-rectal activity in man during rectal infusion of saline: a dynamic assessment of the anal continence mechanism.

1. Anal and rectal pressures and the external anal sphincter electromyogram were recorded in eighteen normal subjects at rest and during rectal infusion of 1500 ml. saline at a rate of 60 ml./min. 2. During saline infusion, the recordings described a pattern of regular relaxations of the internal sphincter associated with contractions of the rectum and the external anal sphincter. The frequency of ano-rectal pressure fluctuations increased as the infusion progressed. 3. The peaks in rectal pressure were always lower than the lowest anal pressure in all normal subjects tested. 4. External sphincter contractions only occurred in association with 60% of internal anal sphincter relaxations and did not prevent the maximum decrease in anal pressure. These observations suggest that phasic contraction of the external anal sphincter does not play a major role in maintaining continence.

Anal Canal↗
PubMedDate not supplied

Endothelin: a long-acting local constrictor hormone.

Endothelin is a local peptide hormone produced by vascular endothelial cells and is the most potent vasoconstrictor yet identified. There is increasing evidence that endothelin plays a role in the regulation of vascular tone and blood pressure and in the pathophysiology of cardiovascular, renal and respiratory disease.

Amino Acid Sequence↗