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C T Speakman

Publications and source records attributed to C T Speakman.

At least 19 recordsLinked to original sources
PubMed2001

Glutathione-S-transferase gene polymorphisms in colorectal cancer patients: interaction between GSTM1 and GSTM3 allele variants as a risk-modulating factor.

The distribution of polymorphisms in the glutathione S-transferase (GST) family genes has been studied in 355 healthy controls and 206 cancer (59 proximal and 147 distal) patients. All controls were subjected to flexible sigmoidoscopy. Odds ratios (OR) after stratification by age, gender and smoking were slightly higher in the cancer group as a whole for GSTM1-null (*0/*0), GSTT1-null (*0/*0) and GSTM3 *A/*B or *B/*B when compared with the control group, but the differences did not reach statistical significance. GSTP1 variants had no effect. Separate analysis of patients with proximal and distal tumours has shown stronger associations for the distal cancers, the GSTM3*B allele presence being significantly more frequent in these patients [OR = 1.77; 95% confidence interval (CI) = 1.15-2.74]. Taking into account strong linkage between the GSTM1*A and GSTM3*B alleles, a separate analysis of the GSTM1-nulled individuals was undertaken. The combination of GSTM1-null genotype with GSTM3*B allele presence (*A/*B or *B/*B) was significantly overrepresented among patients with proximal and distal tumours taken together (OR = 2.12; 95% CI = 1.24-3.63), and especially in distal cancer patients (OR = 2.75; 95% CI = 1.56-4.84). Male individuals displayed a stronger association between the presence of the GSTM1-null in combination with GSTM3 *A/*B or *B/*B and distal tumours with a higher odds ratio (OR = 3.57; 95% CI = 1.73-7.36). In contrast, the frequency of GSTM1 *B/*0 or *B/*B combined with GSTM3 *A/*A was significantly lower in patients with distal colorectal cancer, especially in males (OR = 0.37; 95% CI = 0.15-0.92). Neither of these combinations was associated with proximal tumours. Our findings suggest that interactions of polymorphic genotypes within the GSTM gene cluster affect individual susceptibility to colorectal carcinogenesis, the GSTM3*B variant presence being a risk factor especially in combination with the GSTM1-null genotype.

Alleles↗
PubMed2000

K-ras mutations, rectal crypt cells proliferation, and meat consumption in patients with left-sided colorectal carcinoma.

It has been suggested that N-nitroso compounds derived from meat may increase the risk of K-ras mutations in the human colon. We sought evidence of associations between red meat consumption, frequency and type of K-ras mutations in resected tumours, and the rate of crypt cell proliferation (CCP) in the normal mucosa of patients with left-sided colorectal carcinoma. Meat consumption was assessed by food frequency questionnaire, and CCP was determined in rectal biopsies obtained prior to surgery. K-ras mutations in the resected tumours were determined using a PCR-based oligonucleotide hybridization assay. Fifteen K-ras mutations were detected in tumours from 43 patients; 13/15 in codon 12, 3/15 in codon 13, and 1/15 in both codons 12 and 13. All mutations were G-->A or G-->T transitions. There was no statistically significant difference between intakes of red meat in patients with a K-ras mutation (92.4 +/- 9.7 g/day) and those without (82.3 +/- 7.7 g/day). Rectal CCP was significantly higher in patients than in healthy controls, but there was no correlation with meat consumption or K-ras mutation. These data do not support the hypothesis that meat consumption is a risk factor for acquisition of K-ras mutations during colorectal carcinogenesis.

Aged↗
PubMed1997

Pharmacology of the internal anal sphincter and abnormalities in faecal incontinence.

Studies of anorectal physiology and in-vivo experiments on the innervation of the anorectum have provided considerable information about anorectal function. Additional information regarding the receptors and nerves involved in the control of the internal anal sphincter function has been obtained from in-vitro studies of isolated muscle strips of the internal anal sphincter.

Acetylcholine↗
PubMed1995

Abnormal internal anal sphincter fibrosis and elasticity in fecal incontinence.

PURPOSE: We aimed to investigate the changes in the proportion of collagen and in the elasticity of the internal anal sphincter in patients with neurogenic fecal incontinence. METHODS: Collagen content was studied in ten patients with neurogenic fecal incontinence (mean age, 51.5 years) and ten controls (age, 58.6 years) using histologic techniques to determine differences between incontinence and health and to determine the effect of aging. Changes in elasticity were also measured in 8 controls (mean age, 63 years) and 13 patients with neurogenic incontinence (mean age, 60 years) by recording the in vitro length-tension relationship of the freshly excised internal anal sphincter. RESULTS: Incontinent patients had a significantly higher collagen content than controls (55 percent vs. 33 percent; P = 0.013). In incontinent patients the amount of collagen and the patients' ages correlated significantly (P = 0.001). There was a greater increase in stable tension per increase in muscle length in the strips from incontinent patients compared with controls. CONCLUSIONS: Changes in fibrous tissue content are likely to influence muscle tone and responsiveness of the sphincter in fecal incontinence.

Adult↗
PubMed1994

Effect of age, sex and parity on anorectal function.

Ninety-one healthy subjects (51 women; age range 16-85 years) were studied prospectively to determine the effect of age, sex and parity on anorectal function. Maximum resting pressure, voluntary contraction pressure, rectal sensation to distension, rectal and mid-anal electrosensitivity, perineal descent, pudendal nerve terminal motor latency and fibre density of the external and sphincter were measured. Sex influenced mean(s.d.) voluntary contraction pressure (148(56) versus 95(43) cmH2O for men versus women, P < 0.0001), perineal descent on straining (1.0(0.5) versus 1.3(0.4) cm, P = 0.02) and fibre density (1.43(0.14) versus 1.52(0.15), P = 0.02). Age influenced resting pressure (r = -0.43, P = 0.0001), perineal position at rest (r = -0.55, P < or = 0.0001), mid-anal electrosensitivity (r = 0.42, P = 0.0001) and rectal electrosensitivity (r = 0.54, P < 0.0001). Parity affected mean(s.d.) voluntary contraction pressure (105(53) versus 75(20) cmH2O for nulliparous versus parous women, P = 0.04) and mid-anal electrosensitivity (5.3(2.3) versus 4.5(2.3) mA, P = 0.02). Increasing age leads to perineal descent at rest, slowed pudendal nerve conduction, a fall in resting anal pressure and decreased anorectal sensory function. Women have a lower and squeeze pressure, greater perineal descent, longer pudendal nerve terminal motor latency and a greater muscle fibre density than men. Parity leads only to lower squeeze pressure.

Adolescent↗
PubMed1994

Audit of postanal repair in the treatment of fecal incontinence.

PURPOSE: The short-term results of postanal repair for idiopathic fecal incontinence are satisfactory but data on long-term outcome are lacking. This study was carried out to document the short-term and long-term results of this operation and to determine whether preoperative tests predict long-term outcome. METHODS: Thirty-six patients (33 females; mean age, 57 years) with major idiopathic fecal incontinence operated on by one surgeon were studied. Patients had resting and voluntary contraction anal pressures and pudendal nerve terminal motor latencies (PNTML) measured preoperatively. Symptoms were evaluated at 6 months after operation and again at a median of 25 (range, 6-72) months in all 36 patients. Symptoms were classified as: Group C, no improvement or worse; Group B, minor improvement; and Group A, marked improvement in comparison to the patient's preoperative symptoms. Seventeen patients had postoperative physiology performed. RESULTS: At 6 months there were 6 (17 percent) patients in Group C, 12 (33 percent) in Group B, and 18 (50 percent) in Group A. At final follow-up there were 17 (47 percent) in Group C, 9 (25 percent) in Group B, and 10 (28 percent) in Group A. Comparison of the preoperative data in the final outcome groups showed (mean +/- SE): Groups A and B vs. Group C--resting pressure, 24.6 +/- 6 cm H2O vs. 40.5 +/- 12.2 (P = 0.2), voluntary contraction pressure, 23.7 +/- 5.7 vs. 11.8 +/- 3.6 (P = 0.09), and PNTML, 3.2 +/- 0.75 mS vs. 3.3 +/- 0.99 (P = 0.8). Mean differences between post-operative and preoperative results were: resting pressure, 28 +/- 8.2 cm H2O (P = 0.003); voluntary contraction pressure, 19.5 +/- 6.7 (P = 0.01); and PNTML, -0.3 +/- 0.29 mS (P = 0.3). CONCLUSIONS: At 6 months 83 percent of patients had obtained some benefit from postanal repair but only 53 percent maintained this improvement with only 28 percent being markedly better. There was a trend toward a more favorable outcome in patients with greater squeezing pressures preoperatively but other tests were not of long-term predictive value.

Anal Canal↗
PubMed1993

Neuropeptides in the internal anal sphincter in neurogenic faecal incontinence.

The internal anal sphincter has both an intrinsic and extrinsic innervation which modulates its activity. While the nature of the extrinsic innervation has been well characterised, the same is not true of the intrinsic innervation. Although a variety of neurotransmitters have been identified in the human internal anal sphincter, their physiological role in health, and possible involvement in disease processes, have received little attention. Using immunohistochemistry we have studied the distribution and nerve fibre densities of a range of neuropeptides in the internal anal sphincter from 12 cancer patients (controls) and from 16 patients with neurogenic faecal incontinence. We have also studied the in vitro effect of vasoactive intestinal peptide, neuropeptide tyrosine, and galanin on isolated preparations of the internal anal sphincter from 11 cancer controls and 5 patients with neurogenic faecal incontinence. There was no difference in either the distribution or density of the neuropeptides between the 2 groups of patients, and there was no qualitative difference in the in vitro responses of the sphincter to the neuropeptides. These findings suggest that these neuropeptide components of the intrinsic innervation of the internal anal sphincter are unaffected in patients with neurogenic faecal incontinence.

Anal Canal↗
PubMed1993

Rectal sensory evoked potentials: an assessment of their clinical value.

To assess abnormalities of sensory conduction in anorectal disease we have evaluated peripheral sensory perception and somatosensory evoked potentials produced by rectal stimulation in control subjects and patients with either constipation or idiopathic faecal incontinence. Evoked potentials were also recorded after posterior tibial and dorsal genital nerve stimulation. Rectal sensation was also assessed using electrical stimulation. Reproducible evoked potential recordings after anorectal stimulation were possible in only a minority of subjects and when recorded showed intersubject and intrasubject variation. In the constipated group there was a significant difference in rectal electrical sensation (P < 0.05) from controls. We conclude that peripheral sensory testing demonstrates an abnormality in severe constipation. However, cerebral evoked potentials cannot be reliably recorded after rectal stimulation, and when recorded the latencies are of too broad a range to discriminate between health and disease. This probably relates to the difference between somatic and visceral pathways.

Adult↗
PubMed1993

Abnormalities of innervation of internal anal sphincter in fecal incontinence.

Physiological and histological studies have shown that the internal and sphincter is abnormal in idiopathic fecal incontinence. We have recently demonstrated that the in vitro contractile response of the internal anal sphincter to the sympathetic neurotransmitter noradrenaline is decreased in incontinence. In this study we have further defined this reduced sensitivity and provided more information about the intrinsic innervation in both the normal and the incontinent sphincter muscle. Muscle strips from 12 incontinent patients undergoing post and repair and from 11 controls undergoing rectal excision for low rectal carcinoma were studied. Responses to noradrenaline were recorded initially alone and then in the presence of phentolamine, an alpha-adrenoceptor blocker. In the presence of phentolamine, noradrenaline caused relaxation: there was no significant difference in the relaxation-response curves and the EC50 was the same in the two groups. These results demonstrate that the previously documented reduced sensitivity to noradrenaline is due to an altered sensitivity of the alpha-adrenoceptors. Electrical field stimulation produced relaxations in all muscle strips, but only in the controls was the magnitude of the relaxation significantly increased in the presence of phentolamine. This indicates that there is an alpha-adrenergic excitatory component of the response to electrical field stimulation of the intramural nerves, which was present in tissues from control patients but which was absent in tissues from patients with idiopathic fecal incontinence.

Anal Canal↗
PubMed1993

Abnormal visceral autonomic innervation in neurogenic faecal incontinence.

Changes of denervation in the anal sphincter striated and smooth muscle in patients with neurogenic faecal incontinence are well established. This study aimed to determine if there is also a more proximal visceral autonomic abnormality. Thirty women with purely neurogenic faecal incontinence (prolonged pudendal nerve latencies and an intact sphincter ring) and 12 patients with neuropathic changes together with an anatomical disruption were studied. Two control groups consisted of 18 healthy volunteer women and 17 women with normal innervation but an anatomically disrupted sphincter. Rectal sensation was assessed using balloon distension and electrical mucosal stimulation, and anal sensation by electrical stimulation. Rectal compliance was studied to determine whether sensory changes were primary or caused by altered rectal wall viscoelastic properties. Anal canal pressure changes in response to both rectal distension and rectal electrical stimulation were measured to assess the intrinsic innervation of the internal anal sphincter. Patients with neurogenic incontinence alone had impaired rectal sensation to distension (53.1 v 31.5 ml, p < 0.05, neurogenic v controls) and to electrical stimulation (24.4 v 14.8 mA, p < 0.005). Patients with neurogenic incontinence and sphincter disruption also showed impaired sensation compared with healthy controls (55.8 ml v 31.5 ml, p < 0.05 and 22.9 mA v 14.8 mA, p < 0.05). Patients with only a disrupted sphincter had normal visceral sensation to both types of testing. Both rectal compliance and the response of the internal anal sphincter to rectal distension and electrical stimulation were normal in all patient groups. This study suggests that there is a visceral sensory abnormality in patients with neurogenic incontinence which is not caused by altered rectal compliance. As evaluated in this study the intrinsic innervation of the internal anal sphincter is not affected in this process.

Adult↗
PubMed1992

Decreased sensitivity of muscarinic but not 5-hydroxytryptamine receptors of the internal anal sphincter in neurogenic faecal incontinence.

Previous studies of the internal anal sphincter in patients with neurogenic faecal incontinence have indicated an abnormality of the adrenergic innervation, but little is known about the responsiveness of other receptors in the internal and sphincter in this condition. In this study the in vitro sensitivity to carbachol and 5-hydroxytryptamine (5-HT) of muscle strips from patients with neurogenic incontinence (n = 6 and n = 7) and from control patients (n = 9 and n = 10) was examined. Preparations of internal and sphincter from patients with incontinence were less sensitive to the relaxant actions of carbachol than preparations from the control group. The pD2 value for carbachol (i.e. the negative logarithm of the concentration for half-maximal response) was significantly greater in the controls than in the incontinent group (mean(s.e.m.) 6.03(0.15) versus 5.43(0.24), P < 0.05). There was no significant difference in the contractile responses to 5-HT, which had pD2 values of 6.93(0.13) and 6.63(0.27) for the control and incontinent groups respectively. The unaffected state of the 5-HT receptor and the subsensitivity of the muscarinic receptor are discussed in relation to intrinsic neural control of the internal and sphincter in neurogenic faecal incontinence.

Adult↗
PubMed1992

Abdominal rectopexy for complete prolapse: prospective study evaluating changes in symptoms and anorectal function.

The effect of abdominal rectopexy on bowel function is difficult to assess in retrospective studies because preoperative bowel habit cannot be determined accurately. This study examined bowel symptoms and physiologic tests of anorectal function prospectively in 23 patients before and at three months after rectopexy. Rectopexy eliminated complete prolapse in all and stopped bleeding in 16 of 18 patients. Incontinence improved significantly. Constipation (less than 3 bowel actions per week or straining for more than 25 percent of defecation time) was relieved in 4 of 11 affected patients but developed in 5 of the 12 who were not constipated preoperatively. Since the median bowel frequency was 21 motions per week before surgery and 17 afterward, the main determinant of constipation was straining. Abdominal pain was relieved after rectopexy in 6 of 12 patients but developed in 3 of 13 who were pain-free before surgery. Three patients (13 percent) had a first-degree relative with rectal prolapse. Perineal descent decreased significantly. Maximal anal resting pressure increased significantly, but this did not correlate significantly with improved continence. Twenty-one patients (91 percent) could expel a 50-ml balloon preoperatively; 18 of those 21 could still do so postoperatively. The two patients who could not expel the balloon preoperatively were able to do so postoperative. This study shows that rectal prolapse is associated with profoundly abnormal defecation and abdominal pain. While abdominal rectopexy improved continence, it may improve or worsen other bowel symptoms, including constipation.

Abdominal Pain↗
PubMed1991

Confirmation of endosonographic detection of external anal sphincter defects by simultaneous electromyographic mapping.

Anal endosonography was performed in 13 consecutive patients with post-traumatic faecal incontinence. Thirteen acoustic defects in the external anal sphincter (two hyperechoic, four of mixed echogenicity and seven hypoechoic) were analysed electromyographically by locating under ultrasound guidance the tip of a concentric needle within the defect. The electromyographic activity in this zone was compared with ultrasonically normal muscle. Eleven of 13 sonographic defects showed no electrical activity on electromyography, there was one technical electromyography failure, and one defect was too deep to be reached by the electromyography needle. The electromyographic response was normal in each case within ultrasonically normal muscle. Anal endosonography is recommended as the initial investigation to locate defects, which may be confirmed electromyographically thereby limiting the number of painful needle insertions required for complete mapping of the external anal sphincter.

Adult↗