Selecting patients with faecal incontinence for anal sphincter surgery: the influence of irritable bowel syndrome.

AIM: This was a prospective study to determine the prevalence of irritable bowel syndrome (IBS) in patients with faecal incontinence and to investigate the association of IBS positivity with sphincter dysfunction. METHOD: Patients with faecal incontinence were referred for physiological assessment and further management. Those with an acute obstetric injury, rectal prolapse or previous anorectal surgery were excluded. One hundred and seventy-seven women were studied. Symptom questionnaires were used prospectively to identify IBS positivity using Rome 11 criteria and the Cleveland Clinic incontinence score. RESULTS: The prevalence of IBS was 44%. IBS patients had higher incontinence scores than non-IBS patients (11.0 vs 9.0, P < 0.01). A normal or high maximum resting anal pressure in an incontinent woman increased the chance of her having IBS by a factor of 2.6. CONCLUSION: The prevalence of IBS positivity in patients presenting with faecal incontinence was high. A normal or high anal resting pressure and a high incontinence score should raise the suspicion of IBS.

Potential histamine H2-receptor antagonists. 3. Methylhistamines.

Syntheses are described for all the mono- and some di- and trimethylhistamines. New methods are given for the known Npi, Ntau-, Nalpha-, 2-, and 4-methylhistamines and for the novel compounds, beta-methyl-, 4,Nalpha-dimethyl-, and 4,Nalpha,Nalpha-trimethylhistamines. Agonist activities are reported for stimulation of histamine H1 (guinea-pig ileum) and H2 (rat gastric acid secretion) receptors. H2-Receptor agonist activities indicate that a methyl group is more readily accommodated at the 4 and Nalpha positions than elsewhere in the histamine molecule and that receptor binding is substantially retained with a methyl substituent in these positions. Thus, for the design of potential antagonists, two sites are identified as being worthwhile exploring for the introduction of lipophilic substituents.

Potential histamine H2-receptor antagonists. 4. Benzylhistamines.

As part of our studies aimed at designing histamine H2-receptor antagonists, the effect on histaminergic activity of introducing benzyl substituents at various positions in the histamine molecule is described. New synthetic methods are reported for the novel 4-benzyl-, beta-benzyl- and 4,N tau-dibenylhistamines and the reported 2-benzylhistamine. The novel N tau-benzylhistamine was synthesized by the versatile route reported by us for the synthesis of N tau-methylhistamine. These benzylhistamines, together with the reported N alpha- and N pi-benzylhistamines, were tested for agonist and antagonist activity at both H1 and H2 receptors. The results obtained indicate that introduction of a benzyl group into the histamine molecule causes a marked reduction in H1- or H2-agonist activity, and none of the compounds showed consistent antagonist activity. Evidently, the sterically demanding benzyl substituent is not easily accommodated in the agonist binding mode and is unable to locate a lipophilic receptor region for potential hydrophobic binding.

Linkage studies suggest a possible locus for bipolar disorder near the velo-cardio-facial syndrome region on chromosome 22.

Velo-cardio-facial syndrome (VCFS) is a congenital anomaly characterized by multiple dysmorphisms, cleft palate, cardiac anomalies, and learning disabilities, that results from a microdeletion of chromosome 22q11. An increased prevalence of psychiatric illness has been observed, with both schizophrenia and bipolar disorder commonly being diagnosed. For these reasons, the VCFS region is an interesting candidate region for bipolar disorder. We examined this region in 17 bipolar families from three populations: 13 families from the general North American population (University of California, San Diego/University of British Columbia, UCSD/UBC), three larger families from New York, and a portion of Old Order Amish pedigree 110. Three microsatellite markers spanning 13 cM around the VCFS region were genotyped in all the families. A maximum lod score of 2.51 was obtained in the UCSD/UBC families under a dominant model at D22S303. In the combined family set, maximum lod scores of 1.68 and 1.28 were obtained at this marker under dominant and recessive models, respectively. Four additional markers were subsequently typed in selected positive families, and yielded positive lods at 6 of 7 markers spanning 18 cM in this region. Nonparametric, multipoint analyses using the affected pedigree member (APM) method also yielded suggestive evidence for linkage in both the UCSD/UBC family set (P = 0.0024) and in the combined families (P = 0.017). Affected sibpair analyses were similarly positive in the UCSD/UBC families (P = 0.017), and in the combined families (P = 0.004). These results are suggestive of a possible locus for bipolar disorder near the VCFS region on chromosome 22.

An evaluation of a direct access flexible fibreoptic sigmoidoscopy service.

During a 3 year period 146 general practitioners referred 630 patients to a direct access flexible sigmoidoscopy clinic. The yield was 53.3% with significant colonic or rectal pathology in 30%. Twenty six cancers, 4 Dukes' A, and 38 patients with symptomatic adenomatous polyps were detected. Five further cancers were detected by subsequent barium enemas. The service reduced delay in diagnosing colorectal pathology but did not reduce the number of barium enemas requested by general practitioners. It is suggested that where facilities are already available, such a service to investigate rectal bleeding in patients over 40 years is of benefit both to patients and general practitioners.

Association between Streptococcus milleri and abscess formation after appendicitis.

Abscesses after appendicitis occur in some patients despite timely surgery and antibiotics. The Streptococcus milleri group of bacteria are commonly associated with gastrointestinal abscesses. This study investigated the relationship between S. milleri and abscess formation after appendicectomy a total of 301 patients (172 males, 129 females, median age 22 years) with appendicitis were identified retrospectively from the hospital PAS computer system who had an appendicectomy and peritoneal bacteriology swabs taken. All but one patient had prophylactic antibiotics. Patients were divided into three groups according to peritoneal bacteriology: group 1 (S. milleri +/- mixed faecal organisms, n = 61); group 2 (mixed faecal organisms, n = 126); and group 3 (sterile, n = 114). The chi squared and Student t-tests were used for statistical analysis. Thirteen (21%) of group 1 patients developed an intra-abdominal abscess compared with 4 (3%) in group 2 and 2 (1.7%) in group 3 (P < 0.0001). There was no difference in the prevalence of gangrenous or perforated appendicitis between groups 1 and 2 (56% versus 52%) but these worse forms of appendicitis were less common in group 3 (22%). Group 1 patients had a mean total hospital stay of 10 days versus 6 days for group 2 and 4 days for group 3 (P < 0.001). S. milleri was associated with a 7-fold increase in abscess formation after appendicectomy and a longer hospital stay. Antibiotic prophylaxis did not prevent this complication.

Intracorporeal laparoscopic resections for colorectal cancer: report of cases of abdominoperineal rectal excision and right hemicolectomy with 2 year follow-up.

Techniques for total intracorporeal laparoscopic abdominoperineal excision of rectum and right hemicolectomy for colorectal cancer are described in two patients with 2-year follow-up. Potential advantages over laparoscopically assisted procedures may be offset by increased operating time and expense for right hemicolectomy but the laparoscopic approach seems well suited to abdominoperineal rectal excision. The use of a secure retrieval system is advocated for specimen removal after right hemicolectomy.

Techniques in evacuation proctography in the diagnosis of intractable constipation and related disorders.

A technique of evacuation proctography using a simple barium and air mixture is described. The study can be easily combined with a barium enema examination. A series of 35 patients with intractable constipation have been studied and compared with 7 controls. Most of the abnormalities seen using more elaborate methods of defaecography were identified. Variants of rectal intussusception were found in 16 patients. Other diagnoses included rectocele, mucosal and full rectal prolapse, accentuation of puborectalis impression and solitary rectal ulcer. The technique should prove useful in the management of patients with disorders of defaecation.

Preoperative staging of local invasion in rectal cancer using endoluminal ultrasound.

Digital examination is the most commonly used method of assessing local invasion in rectal cancer, but it is highly subjective and accuracy is related to surgical experience. The use of transrectal ultrasound in the preoperative staging of rectal cancer has been assessed in 51 patients with histologically proven rectal cancers. Results showed a high degree of correlation when compared with postoperative histopathology (r = 0.91, P less than 0.001). Invasion beyond the muscularis propria was predicted with a sensitivity of 97%, specificity of 92% and predictive value of 97%.

Short course preoperative radiotherapy is the single most important risk factor for perineal wound complications after abdominoperineal excision of the rectum.

AIM: To determine factors associated with perineal wound complications following abdominoperineal excision of the rectum (APER) for rectal adenocarcinoma and their effects on time to healing. PATIENTS AND METHODS: We studied all cases of APER performed in our unit by four consultants over 7 years. Seven out of nine factors considered important in wound healing were analysed using logistic regression and a multivariate model was built to examine interactions. Wound persistence was calculated using the Kaplan-Meier method. RESULTS: Data were available for 94 of 96 patients [male:female, 3:2, median age 72.5 (IQR: 64-78)]. Thirty-nine (41%) patients had 25 Gray, 3-portal, fractionated 5-day short course preoperative radiotherapy (SCPRT). Dukes stages were A (34%), B (26%), C (40%). Perineal wound complications occurred in 44 (47%), 16% of these requiring return to theatre. Local recurrences occurred in 13 (15%). There was no evidence to suggest that either patient gender, age, smoking status, preoperative albumin or haemoglobin level, or T stage were associated with the development of wound complications. The odds of wound complications for a patient who had SCPRT was over 10 times that for a patient who did not have preoperative radiotherapy (odds ratio 10.15, 95% CI: 3.80-27.05, n = 94). Seventy-four per cent of SCPRT and 96% of non-SCPRT wounds had healed by 1 year. Estimated failed wound healing rates at 30 and 90 days were 64% (95% CI: 46-78) and 48% (95% CI: 30-64) in SCPRT patients compared with 23% (95% CI: 12-35) and 9% (95% CI: 3-20) in non-SCPRT patients (log rank test P < 0.0001). CONCLUSION: Patients who have an APER are over 10 times more likely to have a perineal wound complication if they have SCPRT than not. Two-thirds of these will not have healed by 1 month, half by 3 months and over a quarter will still remain unhealed at 1 year. This has important implications for patient management decisions. Large prospective studies are needed to evaluate the effects of a selective policy for radiotherapy administered to patients requiring APER.

SK&F 92657, a novel antihypertensive acting by precapillary vasodilatation and beta-adrenoreceptor blockade.

1. The properties of a new antihypertensive agent, SK&F 92657, DL-3-[2-(3-t-butylamino-2-hydroxypropoxy)phenyl]-6-hydrazinopyridazine, have been studied. 2. The compound caused a sustained fall in blood pressure in several species as a result of precapillary vasodilatation, particularly in the renal and coronary vasculatures. 3. The beta-adrenoreceptor-blocking actions of SK&F 92657 prevent reflex cadiac stimulation.

Slow transit constipation. Comparison between patients with or without previous hysterectomy.

We have studied 31 patients with slow transit constipation. Fourteen developed severe symptoms following a hysterectomy, while the remainder had symptoms arising de novo and unrelated to pelvic surgery. To establish whether there were specific abnormalities which might be linked to hysterectomy, we compared the two groups. Rectosigmoid motility was impaired in the de novo group. Functional sphincter length, maximum resting anal canal pressure, and the rectoanal inhibitory reflex were not significantly different from controls. The majority of patients were able to significantly increase the anorectal angle on straining to defecate. Patients in the de novo group had a higher sensory threshold for rectal filling compared with controls, whereas the posthysterectomy group was not significantly different. Electromyography of the external sphincter showed failure of appropriate inhibition of resting activity in 57% of the de novo and 38% of posthysterectomy patients. The de novo group had hypoactivity of the rectosigmoid and an insensitive rectum. The abnormality in the hysterectomy group is less clear and any precise link between slow transit constipation and hysterectomy remains obscure.

The relationship between perineal descent and denervation of the puborectalis in continent patients.

It has been suggested that perineal descent causes puborectalis neuropathy. To elucidate this, perineal descent was measured on standard proctograms and prolongation of mean motor unit potential duration was used as the index of denervation of the external sphincter and puborectalis in 9 male and 18 female patients with perineal descent and obstructed defaecation. The findings were compared with 21 normal controls. There was no significant perineal descent below the pubococcygeal line at rest but both males and females had abnormal descent of the anorectal angle on straining and a similar degree of external sphincter neuropathy. Females, however, exhibited a significant degree of puborectalis denervation compared with controls (p less than 0.001) and with male patients (p less than 0.001). Thus external sphincter denervation was associated with perineal descent in both sexes whereas other causes, of which obstetric trauma is a possibility, must be implicated in the puborectalis neuropathy of the females studied.

New method for assessment of anal sensation in various anorectal disorders.

A new technique for quantifying anal sensation utilizing mucosal electrosensitivity is described and has been tested in 97 patients. Normal subjects (n = 20) have a sensory threshold varying from 2 to 7.3 mA being most acute in the region of the anal valves. Sensory awareness also extends into the upper anal canal. Patients with neuropathic incontinence (n = 17) have a sensory deficit (P less than 0.002) whilst patients with haemorrhoids (n = 28) have less sensitive mucosa displaced into the upper anal canal (P less than 0.0001). Patients with acute fissure-in-ano (n = 10) have lower thresholds of sensation at the site of the fissure and slow transit constipation patients (n = 22) have normal anal sensation. The technique is reproducible and should prove useful in the investigation of anorectal disorders.

Structure of the beta-blocker/vasodilator agent prizidilol, DL-6-(2-[3-(tert-butylamino)-2-hydroxypropoxylphenyl)-3-pyridazinylhydr azine hemisulfate monohydrate.

Prizidilol, a compound combining vasodilator and beta-blocker functionalities in the same molecule, has been synthesized and characterized by Smith Kline and French Research Ltd. Crystal data: C17H25N5O2 x 1/2H2SO4 x H2O, M(r) = 398.47, orthorhombic, a = 10.722 (2), b = 11.635 (6), c = 34.105 (3) A, V = 4254.61 A3, Pbnm (non-standard form of Pnma) (D16(2h), No. 62), Z = 8, F(000) = 1704, Dx = 1.244 Mg m-3, mu(Cu K alpha) = 11.673 cm-1, R = 0.064 for 2432 independent reflections with I > 3 sigma(I). Prizidilol shows strong conformational similarities to propranolol and is protonated at the secondary amine. The 6-phenyl-3-hydrazinopyridazine residue is not planar. The hydroxy group at the asymmetric carbon is disordered so that both enantiomers are found at each molecular site. The sulfate ions and disordered water molecules lie in the crystallographic mirror plane.

Diagnosis and surgical management of intractable constipation.

Seventy-four patients with intractable constipation, of whom thirty-three had slow and forty-one normal intestinal transit, were investigated to determine the aetiology of their disorder and plan treatment. Patients with slow transit had a greater incidence of abdominal pain and distension (P less than 0.001) and only 9 per cent had a normal call to stool compared with 71 per cent of those with normal transit (P less than 0.001). Internal and sphincter function as assessed by sphincter pressures, length and the recto-anal inhibitory reflex did not reveal any difference between the groups and normal controls; similarly anal sensation and rectal compliance were normal. However, those with normal transit had a higher threshold of rectal sensation than controls (P less than 0.05). Slow transit patients failed to show a postprandial increase in rectosigmoid motility compared with controls (P less than 0.05). Whilst the majority failed to inhibit the external sphincter on bearing down, half of those with normal transit produced either partial or complete inhibition. Both groups were able to increase the anorectal angle on straining. Twenty-two normal transit patients had abnormal perineal descent compared with controls (P less than 0.0005). Patients with perineal descent exhibited abnormal rectal morphology. Rectal intussusception was observed in 13 of 35 evacuation proctograms. On the basis of the data presented, we could not justify internal sphincterotomy of puborectalis division. Our policy in severe slow transit constipation was to offer colectomy and ileorectal anastomosis. In five out of seven to date, a successful result has been achieved. Eight patients with rectal intussusception have undergone an abdominal rectopexy with significant improvement in three. In our hands, the evacuation proctogram and transit studies were the most useful preoperative investigations.

Reversal of Hartmann's procedure: timing and operative technique.

A review of closure of Hartmann's colostomy was undertaken to establish guidelines for the timing and technique of reversal. Between 1984 and 1990 there were 69 reversals; 48 patients originally had diverticular disease and 21 had carcinoma. One-third underwent reversal before 4 months and two-thirds after this time. The operative mortality rate was 3 per cent and the anastomotic leak rate 4 per cent. Significant morbidity occurred in 30 per cent. There was no advantage in delayed closure. Complications occurred in 24 per cent of patients undergoing reversal before and 35 per cent undergoing reversal after 4 months. Thirty-five anastomoses were hand-sewn and 34 stapled. There were no differences in operating time for the two techniques, but a greater number were stapled after 4 months than before (P less than 0.05), which may reflect increased rectal stump shrinkage with time. There were no differences in complication rates whether the anastomosis was hand-sewn (34 per cent) or stapled (26 per cent). Closure of Hartmann's colostomy is a safe procedure but has a significant morbidity in nearly one-third of cases. On the basis of these results, there is no indication to delay closure after 4 months have elapsed, and earlier reversal, when the rectal stump is most accessible, is recommended.

Assessment of microtransducers in anorectal manometry.

It has been reported that microtransducer-tipped catheters (transducer) produce reliable reproducible measurements which correlate well with water-filled balloon systems. Maximum resting pressure (MRP) and maximum voluntary contraction pressures (MVC) were compared using a standard station pull-through technique in 12 patients. There was a poor correlation for both MRP: microballoon, 115 cmH2O (60-160 cmH2O); transducer 60 (20-110), r = 0.62, P less than 0.05, and MVC: microballoon, 202 (60-375); transducer, 175 (60-210), r = 0.42, n.s. To determine whether this was due to radial variation in pressures measured by the transducer, we studied a further 39 patients with both systems. At each station, transducer measurements were made at each of four quadrants. We found better correlation for MRP: microballoon, 100 (40-175); transducer, 66 (34-120), r = 0.72, P less than 0.001, and MVC: microballoon, 225 (55-650); transducer, 180 (50-470), r = 0.87, P less than 0.001, but a significant radial variation for the transducer where rotation reduced MRP pressure measurements by 21 per cent (0-600 per cent), and MVC 17 per cent (0-76 per cent). Moreover there was a significant difference between anterior and posterior MRP in the upper anal canal, anterior 35 (5-80) versus posterior 25 (10-60), P less than 0.05. These results account for the poor correlation between random positioning of the microtransducer-tipped catheter and indicate that radial orientation must be taken into account.