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Biomedical subjects

H C McKirdy

Publications and source records attributed to H C McKirdy.

At least 19 recordsLinked to original sources
PubMed2001

Vector volume analysis of the lower esophageal sphincter in achalasia and the effect of balloon dilation.

Assessment of the effect of balloon dilation of the lower esophageal sphincter in achalasia currently relies on symptom scores, radiologic studies, or manometry. We have used vector volume analysis which constructs a three-dimensional (3D) pressure profile to examine the effects of balloon dilation on the sphincter. Studies were performed in 26 normal subjects and in 11 patients with achalasia in whom vector volume was determined before and/or after balloon dilation. Vector volume analysis was performed using a multilumen manometry catheter with eight side-reading ports. The catheter was withdrawn through the sphincter using a continuous pull-through technique. A 3D pressure profile was constructed. Vector volume of the lower esophageal sphincter shows a marked radial and linear asymmetry in normal subjects. 3D pressure profiles showed a symmetrical increase in lower esophageal sphincter pressure in untreated achalasia. Mean vector volumes pre and postdilation fell from 254 to 88 cm3 respectively. This was associated with a fall in the mean radial symmetry index from 0.83 to 0.76. Improvement in dysphagia occurred in those patients in whom pressure fell to 15 mmHg or below in at least three adjacent segments. This technique may be a useful tool in the assessment of patients with achalasia and postdilation results may help to predict the long-term outcome of treatment.

Adult↗
PubMed2000

Nitric oxide mediates a therapeutic effect of nicotine in ulcerative colitis.

BACKGROUND: Ulcerative colitis is a condition of nonsmokers in which nicotine is of therapeutic benefit. AIMS: To examine the in vitro effect of nicotine on colonic smooth muscle activity and the role of nitric oxide (NO) as a mediator. METHODS: Nicotine, 1-10 microM, was administered to strips of circular muscle from the distal sigmoid colon of 9 patients with active ulcerative colitis and 18 with colorectal cancer. The effect of electrical field stimulation (EFS) was examined before nicotine was added. Finally L-NAME, a NO synthetase inhibitor, was added before nicotine was administered again. RESULTS: Muscle strips developed similar spontaneous resting tone. In response to EFS, ulcerative colitis tissue developed lower tensions than the controls. Nicotine significantly reduced the resting tone and peak tension after EFS, with a greater effect in controls. With L-NAME, peak tensions were increased more in ulcerative colitis than controls, and nicotine produced a much smaller reduction. CONCLUSIONS: Nicotine reduces circular muscle activity, predominantly through the release of nitric oxide-this appears to be 'up-regulated' in active ulcerative colitis. These findings may explain some of the therapeutic benefit from nicotine (and smoking) in ulcerative colitis and may account for the colonic motor dysfunction in active disease.

Adult↗
PubMed1999

Intra-luminal nicotine reduces smooth muscle tone and contractile activity in the distal large bowel.

BACKGROUND: Nicotine may be of therapeutic value in ulcerative colitis (UC), although its mechanism of action has not been established. OBJECTIVE: To examine the effect of a solution of nicotine on sustained resting pressure (tone) and contractile activity in the human colon. METHODS: Ten healthy volunteers, and seven with UC in symptomatic remission took part; all were non-smokers. All 17 subjects were given nicotine or placebo solution on two separate occasions in a randomized sequence. A water-perfused manometry catheter, with openings at 5, 10 and 15 cm from the tip, was placed by rigid sigmoidoscopy in the recto-sigmoid region. Baseline tone and activity were measured for 15 min prior to instillation of 20 ml of saline alone or with nicotine, 1.2 mg, at pH 4.5. Observations were made over the subsequent 15-20 min. RESULTS: Baseline spontaneous activity in all subjects showed both high- and low-frequency components; in three patients with UC, the low-frequency activity was of high amplitude. The nicotine reduced both tone and activity in all subjects, with reduction or abolition of the large contractions in UC. Tone in all 17 subjects was reduced significantly at 3 min after nicotine (P = 0.000015, sign test); the rate of recovery varied in individuals. Results from normals and UC did not differ significantly from each other. No significant change in tone or activity was observed with the saline solution. CONCLUSION: Intra-luminal nicotine significantly reduces both smooth muscle tone and contractile activity in the recto-sigmoid colon in both normal subjects and patients with UC.

Adult↗
PubMed1994

Inflammation impairs neurally mediated responses to electrical field stimulation in isolated strips of human gallbladder muscle.

Strips from human gallbladder removed at surgery were exposed to cholecystokinin octopeptide CCK-OP 15 nM and were subjected to electrical field stimulation (EFS) in vitro using parameters for selective stimulation of nerves (5- to 10-sec trains of 0.3-msec pulses at 10 Hz). An adjacent strip from the same specimen was processed for histological examination. These preparations were given a numerical score for inflammatory change. The strength of contraction in response to CCK-OP was inversely related to the severity of inflammation. Gallbladders with no response to EFS had a higher inflammation score (median 11, range 5-16) than those with a response (median 7, range 3-12). We conclude that inflammatory changes in human gallbladder impair responses to neural and hormonal stimulation, but we are unable to determine unequivocally in this study whether this is a result of damage to nerves or muscle cells. However, the observation that some strips were able to contract in response to CCK-OP but not to neural stimulation suggests the possibility of neural damage in gallbladder inflammation.

Cholecystitis↗
PubMed1994

Anorectal physiological testing in defecatory disorders: a prospective study.

A prospective study of anorectal physiological testing in 26 patients with obstructed defecation and 20 patients with faecal incontinence was performed. There were overlaps in individual test parameters between the two groups of patients. However, patients with severely blunted rectal sensation (maximum tolerated volume > 300 mL) and anismus were more likely to have obstructed defecation. Patients with very low anal canal pressures, a short (< 2.0 cm) anal canal, bilaterally prolonged (> 2.1 ms) pudendal nerve terminal motor latency and a grossly distorted and canal (vector symmetry index < or = to 0.75) were more likely to have faecal incontinence. Thus, patterns of anorectal physiological test results together with clinical evaluation, rather than individual test measurements, are more valuable in defining the underlying defecatory disorders and providing guidance on therapy.

Adult↗
PubMed1994

Non-adrenergic non-cholinergic inhibitory innervation shown by electrical field stimulation of isolated strips of human gall bladder muscle.

Non-adrenergic non-cholinergic (NANC) inhibitory nerves have been described in all regions of the gastrointestinal tract, but have not been shown previously in the human gall bladder. Electrical field stimulation was used in the presence of various agonists and antagonists to show NANC inhibitory innervation in strips of human gall bladder muscle. Gall bladder strips were set up isometrically in an organ bath containing oxygenated Krebs's solution. Electrical field stimulation was applied at 10 Hz, pulse width 0.3 ms and supramaximal voltage at intervals of 3 to 5 minutes. Of 60 strips that contracted in response to electrical field stimulation, 30 showed relaxation on electrical field stimulation in the presence of either carbachol (5-10 microM) or else atropine (0.5-2 microM) plus cholecystokinin octapeptide (0.01-0.1 microM) or caerulein (0.1 nM) or histamine (5-10 microM). In 22 strips this relaxation was not abolished by guanethidine (2-5 microM) showing the NANC nature of this response. The NANC relaxation was abolished by L-nitroarginine (100 microM) and this effect was partly reversible by L arginine (200 microM). All responses to electrical field stimulation were abolished by tetrodotoxin (0.2-2 microM). These results show for the first time a NANC inhibitory innervation in human gall bladder muscle. The probable neurotransmitter is nitric oxide.

Atropine↗
PubMed1993

Control of the human ileocaecal junction: an in vitro analysis of adrenergic and non-adrenergic non-cholinergic mechanisms.

Circular muscle strips from the human ileocaecal junction developed myogenic tone (sustained resting tension) in vitro and showed an obvious component of relaxation in response to electrical field stimulation. These features are considered typical of sphincteric muscle because circular muscle strips from terminal ileum 1-2 cm proximal to the junction and from the caecum or ascending colon 1-2 cm distal to the junction developed little or no tone and showed predominantly contractile responses to electrical-field stimulation. In 18 out of 29 specimens, junctional strips showed excitatory responses to adrenaline or noradrenaline. The relaxation of junctional strips was non-adrenergic non-cholinergic (NANC) in nature. Nitric oxide appears to be involved in the NANC relaxation.

Electric Stimulation↗
PubMed1992

Evidence for involvement of nitric oxide in the non-adrenergic non-cholinergic (NANC) relaxation of human lower oesophageal sphincter muscle strips.

Electrical field stimulation of circular muscle strips from human lower oesophageal sphincter reveals a predominant relaxation response. This relaxation is non-adrenergic non-cholinergic (NANC). The nitric oxide synthesis-blocking agent N omega-nitro-L-arginine (10-100 microM) reduces or abolishes this NANC relaxation, suggesting involvement of nitric oxide in the response.

Adrenergic Fibers↗
PubMed1988

Novel autonomic neurotransmitters and upper gastrointestinal function.

The evidence for, and possible roles of, inhibitory and excitatory non-adrenergic, non-cholinergic (NANC) nerves supplying smooth muscle, and the effects of putative transmitter candidates are considered for each of three main regions of the upper gastrointestinal tract: (A) the smooth muscle portion of the oesophagus and the oesophagogastric junction, (B) the stomach (fundus, body and antrum) and gastroduodenal junction and (C) the biliary tract and choledochoduodenal junction. The major points from human tissues are as follows: 1. Inhibitory (NANCI) nerves appear to be present in the muscularis externa of oesophagus, stomach and duodenum, with greater density in the circular than in the longitudinal muscle. 2. NANCI nerves are present in high density at the oesophagogastric and choledochoduodenal junctions. They may also be present at the gastroduodenal junction. The gall-bladder may have a very sparse NANCI innervation. 3. Excitatory (NANCE) nerves appear to be present throughout the upper gastrointestinal tract. 4. Many candidates need at present to be considered for the role of NANCE transmitter(s) in the human upper gastrointestinal tract but substance P still seems a likely contender for this role. 5. Fewer candidates are at present generally available for the role of NANCI transmitter(s), with VIP and ATP being leading contenders. However, in the human upper gastrointestinal tract the evidence for ATP is not good, and VIP still remains the favourite candidate except in the gall-bladder, where its role remains to be elucidated.

Animals↗
PubMed1987

Effect of drugs, hormones and electrical field stimulation on isolated muscle strips from human choledochoduodenal junction.

The behaviour of in vitro strips from the human choledochoduodenal junction would appear to be related to the anatomical location of origin of the strip. Strips from the papillary region showed low tone and obvious spontaneous rhythmic contractions (0 X 5-6/min). Strips from the region of the inferior choledochal sphincter showed, in ten out of fifteen specimens, spontaneous myogenic tone and gave a relaxation or a biphasic response (relaxation followed by contraction) to electrical field stimulation (0 X 3 ms pulses at 10 Hz for 5 s). All strips from human choledochoduodenal junction are remarkably insensitive to a variety of gastrointestinal hormones and to opioid agents.

Acetylcholine↗
PubMed1985

Effect of drugs and electrical field stimulation on circular muscle strips from human lower oesophagus.

Sphincteric muscle from human lower oesophagus may be identifiable in vitro by its ability to develop a very high level of tone (sustained resting tension). Circular muscle strips from human lower oesophagus generally behave in a similar manner to strips from the opossum oesophagus with respect to development of tone, responses to electrical field stimulation and responses to a variety of drugs. Pharmacological analysis of responses to field stimulation in strips from the region of the oesophago-gastric junction suggests that the typical biphasic response (relaxation followed by an after-contraction) is mediated by nerves which are neither adrenergic nor cholinergic. Of the substances examined only vasoactive intestinal peptide (VIP) cannot be excluded as a possible candidate for the role of inhibitory transmitter. The mechanism producing the after-contraction is not clear but it would seem unlikely that this is simply a rebound contraction. The after-contraction can be blocked independently of the relaxation by a variety of agents and is potentiated by metoclopramide.

Carbachol↗