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Biomedical subjects

A N Smith

Publications and source records attributed to A N Smith.

At least 19 recordsLinked to original sources

A method of computerised isotope dynamic proctography.

Patients with long-standing constipation were examined by radioisotope proctography. A radiolabelled synthetic potato mash was inserted intrarectally and the dynamic changes during simulated defaecation recorded using a gamma-camera. Computer images from the stored data illustrate changes in the anorectal angle and pelvic floor. The median (and 95% confidence intervals) of the anorectal angles were: at rest 105 degrees (101 degrees, 116 degrees), on voluntary contraction of the pelvic floor by 'squeezing' 91 degrees (81 degrees, 98 degrees), on straining 120 degrees (107 degrees, 137 degrees) and during evacuation 126 degrees (116 degrees, 153 degrees). The pelvic floor movements were: pelvic floor ascent on voluntary contraction 28 mm (9, 34 mm), pelvic floor descent on straining -8 mm (-14, -4 mm) and descent during evacuation -27 mm (-34, -11 mm). Useful additions to previous methods are measurement of the completeness of rectal evacuation 58% (42, 77%), the defaecation time 64 s (50, 138 s) and the defaecation rate 0.9%/s (0.4, 1.4%/s).

Anal Canal

Comparison of triplicated (S) and quadruplicated (W) pelvic ileal reservoirs. Studies on manovolumetry, fecal bacteriology, fecal volatile fatty acids, mucosal morphology, and functional results.

Capacity and compliance, efficiency of evacuation, fecal bacteriology, fecal volatile fatty acids, mucosal morphology, and functional outcome were studied in 20 patients with triplicated (S) and 20 patients with quadruplicated (W) reservoirs after ileal pouch-anal anastomosis. Compared with patients with S reservoirs, patients with W reservoirs were found to have greater efficiency of evacuation of radiolabeled synthetic stool [97% (91%-98%) vs. 74% (62%-89%); P less than 0.05], and their reservoirs were more capacious [350 mL (320-400 mL) vs. 228 mL (175-290 mL); P less than 0.01] and compliant [16.0 mL/cm H2O (13.8-19.0 mL/cm H2O) vs. 12.3 mL/cm H2O (7.4-14.6 mL/cm H2O); P less than 0.01]. Effluent from S reservoirs contained significantly greater numbers of bacteroides (P less than 0.05) and concentrations of acetic and propionic acids (P less than 0.05) than effluent from W reservoirs. The degree of mucosal inflammation and villous atrophy in each design of reservoir was not significantly different. The ratio of anaerobes to aerobes in pouch effluent was significantly correlated with the degree of mucosal inflammation (rs = 0.433; P = 0.035). Fecal volatile fatty acids were significantly correlated with the percentage of stool retained after defecation and degree of mucosal inflammation. The frequency of bowel action was significantly less in patients with W reservoirs than in patients with S reservoirs [3.5/day (3-4/day) vs. 6.0/day (4-7/day); P less than 0.01]. The results indicate marked differences between these two ileal reservoir designs.

Adolescent

The importance of the orientation of the electrode plates in recording the external anal sphincter EMG by non-invasive anal plug electrodes.

Two non-invasive anal plug electrodes of similar size have been compared, one with the electrode plates orientated circularly in the anal canal and the other with the plates in the long axis of the anal canal. There was a significant increase in the amplitude in the EMG signals recorded at rest and during squeeze from the external anal sphincter with a longitudinally placed electrode in 117 patients. Inappropriate contraction of the external anal sphincter when straining at stool was more readily detected using the longitudinal electrode in 52 patients investigated for intractable constipation. The longitudinal electrode detected the amplitude of the response to the elicitation of a pudeno-anal reflex more readily than the circular electrode. When in 12 of the 117 the pudeno-anal reflex EMG signal was either absent or not detected with the circumferential plug electrode, the longitudinal electrode detected the presence of a low amplitude response in 11 of these. When the non-invasive longitudinal electrode was compared to invasive fine wire stainless steel electrodes, a correlation was found for external anal sphincter resting EMG (r = 0.99, p less than 0.01), voluntary squeeze EMG (r = 0.99, p less than 0.001) and strain EMG (r = 0.91, p less than 0.01). The longitudinal anal plug electrode thus facilitates surface acquisition of EMG activity.

Adult

Constipation associated with chronic spinal cord injury: the effect of pelvic parasympathetic stimulation by the Brindley stimulator.

Ten subjects with severe constipation due to complete spinal cord injury (SCI) had prolonged oro-anal transit time (p less than 0.01), diminished faecal water content (p less than 0.05) and a reduced frequency of defaecation (p less than 0.01) compared to 10 non-SCI subjects. Paraplegics with an implanted Brindley S234 anterior sacral nerve root stimulator had a significant increase in frequency of defaecation (p less than 0.01), compared to the SCI group while the faecal water content was less although not significantly so. The Brindley stimulator group also showed a more rapid colonic transit than the SCI group but this did not reach statistical significance. SCI is associated with constipation which therefore appears to be favourably influenced by the Brindley S234 anterior nerve root stimulator. The effects produced are compatible with stimulation of left colonic motility, which facilitates the emptying of the distal colon, but also suggest that part of the response restricts transit in some areas of the colon or rectum. Since the motility changes induced by the Brindley stimulator do not affect the right colon a relatively greater residence time of the faecal bolus in this part of the large bowel would enhance water absorption.

Adult

Complement activation and antibody binding by pneumolysin via a region of the toxin homologous to a human acute-phase protein.

Pneumolysin, a membrane-damaging toxin, is known to activate the classical complement pathway. We have shown that 1 microgram ml-1 of pneumolysin can activate complement, which is a much lower level than observed previously. We have identified two distinct regions of pneumolysin which show homology with a contiguous sequence within acute-phase proteins, including human C-reactive protein (CRP). Site-directed mutagenesis of the pneumolysin gene was used to change residues common to pneumolysin and CRP. Some of the modified toxins had a reduced ability both to activate complement and bind antibody. We suggest that the ability of pneumolysin to activate complement is related to its ability to bind the Fc portion of immunoglobulin G.

Amino Acid Sequence

Outlet obstruction constipation (anismus) managed by biofeedback.

Fifteen subjects presenting with intractable constipation due to obstructive defecation, mean (SEM) duration 8.8 (1.8) years, had the inappropriate contraction and electromyographic changes in the pelvic floor muscles and external and sphincter typical of this condition. An electromyographically derived index was used to grade its severity. A self applied biofeedback device was used to allow electromyographic recording of the abnormal external anal sphincter. The subjects were encouraged to reduce the abnormal electromyographic activity on straining after instruction and training. The procedure was intended as a relearning process in which the non-relaxing activity of the pelvic floor was gradually suppressed. Biofeedback training was maintained on a domiciliary basis for a mean time of 3.1 weeks and resulted in a significant reduction in the anismus index (mean (SEM) 69.9 (7.8)% before biofeedback, mean 14 (3.9)% after biofeedback, p less than 0.01). There was an associated reduction in the time spent straining at stool and in the difficulty of defecation and an increased frequency of defecation. Defecatory video proctograms in six subjects showed improvements in the anorectal angle during straining and evacuation. The clinical benefit to the patients persisted after a mean follow up of 6.2 months.

Adult

Considerations on the further expansion of the AIDS epidemic in South Africa--1990.

An epidemiological composite of the human immunodeficiency virus (HIV) epidemic in South Africa was constructed from reported acquired immunodeficiency syndrome (AIDS) figures, blood donor seroprevalence data and a family of active surveillance studies in the Johannesburg area. Of great concern is the extensive and continuing silent spread of HIV in the urban black population, manifested by doubling times in male and female sexually transmitted disease (STD) clinic attenders of 10.67 and 9.78 months respectively, a doubling time in female family planning (FP) attenders of 6.55 months, and HIV infection rates of 1:56, 1:37 and 1:91, respectively. These data suggest a spread of infection far more extensive than the relatively lower AIDS figures. However, seroprevalence figures in municipal employees of mainly rural origin were considerably lower, only 1:1,250 in black men and none in women, but regular movements between urban and rural areas could well introduce and amplify infection in rural areas. A complete epidemiological picture of HIV can only be attained by employing both the above approach of the family of surveys complemented by a nationwide seroprevalence study to assess HIV penetration into the general 'background' population. Educational interventions should now be particularly targeted to the major risk groups in the urban black heterosexual community.

Acquired Immunodeficiency Syndrome

Highly selective vagotomy 5-15 years on.

Highly selective vagotomy for duodenal ulcer was performed on 307 patients between 1973 and 1983 without operative mortality. Of these, 283 (92.2 per cent) were followed up prospectively for a minimum of 5 years. Recurrent ulcer was diagnosed in 49 (17.3 per cent). The recurrent ulcer rate increased from 13.2 per cent at 5 years to 19.4 per cent at 12 years. Age, length of history, previous haemorrhage or perforation and preoperative acid output were not associated with increased risk of recurrent ulceration. The risk in men and smokers was higher but not significantly so. The recurrence rate for individual surgeons varied from 5.3 to 25.6 per cent. Failure of healing with H2-receptor antagonists was not associated with a higher recurrent ulcer rate. Patients with a strong family history (more than one first degree relative affected) had a significantly higher recurrence rate (33.2 per cent at 10 years) than those without (13.5 per cent at 10 years). Of the 49 recurrent ulcer patients, 30 (61.2 per cent) required either an operation or regular H2-receptor antagonists. Of the 250 patients (81.4 per cent) available in 1988 for review of symptoms 5-15 years after operation, 5.4 per cent had dumping, 8.9 per cent epigastric pain, and 11.8 per cent heartburn every day or most days. H2-receptor antagonists were required by 10.7 per cent of patients on a frequent or regular basis. Of 239 patients who answered the question, 218 (91.2 per cent) felt that their symptoms had been cured or greatly improved and 203 (84.9) considered the operation a success. Despite the high recurrence rate, the operation was successful in controlling ulcer symptoms in around 90 per cent of patients and produced postvagotomy symptoms--none severe--in around 5 per cent of patients.

Adolescent

Strength of the colon wall in diverticular disease.

Studies of the aetiology of diverticular disease of the colon have been focused on intraluminal pressure for almost three decades. It is only relatively recently that the mechanical properties of the wall of the colon have been examined. The tensile strength and elasticity of the colon decline with age and this is the most marked in the left colon which is the narrowest and thickest part. This review discusses the case that the mechanical properties of the bowel wall are key factors in the development of diverticular disease. The potential role of high fibre diets in reducing the pressure changes which may stress the colon wall in this disease is also considered.

Aging

Complications of diverticular disease and non-steroidal anti-inflammatory drugs: a prospective study.

Previous retrospective studies have suggested an association between consumption of non-steroidal anti-inflammatory drugs (NSAIDs) and the complications of diverticular disease. Ninety-two patients were entered into a prospective study of the complications of diverticular disease over a 3 year period; 31 were taking NSAIDs, compared with only four age- and sex-matched controls from a representative general practice (P less than 0.001). A second control group comprised 306 patients with cancer of the colon in whom NSAID consumption was again significantly lower than in patients with diverticular disease (22 of 306 versus 31 of 92, P less than 0.001). Of the 31 patients taking NSAIDs, 19 presented with a perforation or peritonitis. By contrast, only eight of the 61 patients not taking NSAIDs had such complications (P less than 0.001). Eleven patients presented with bleeding of whom five were taking NSAIDs and six were not. Patients admitted with complications of diverticular disease have a high incidence of NSAID intake, and it appears that NSAID consumption is associated with a more severe form of the disease.

Adult

Disordered colorectal motility in intractable constipation following hysterectomy.

Colorectal and anal sphincter motility and electrophysiology were investigated in 14 women with profound constipation following hysterectomy and compared with an asymptomatic group of control subjects. Twelve patients complained of significant urinary symptoms. No differences in the motor function of the anal sphincters were detectable. The latency of the pudendoanal reflex was unchanged after hysterectomy. Proctometrograms demonstrated significantly increased rectal volumes and compliance in the hysterectomy group together with deficits of rectal sensory function. In the basal state a significant proximal-to-distal sigmoid colon motility gradient existed only in the control group. Following stimulation with Prostigmin, this gradient was enhanced in the control group but paradoxically reversed in the hysterectomized patients, thus constituting a functional obstruction. Denervation supersensitivity was demonstrable in two patients tested with carbachol provocation but not in control subjects. These findings suggest dysfunction in the autonomic innervation of the hindgut in some patients who had undergone hysterectomy, resulting in severe constipation.

Adult

Effects of hysterectomy on bowel and bladder function.

A case control study compared the bowel habit of 91 post-hysterectomy women with paired controls from the same family doctor practice. More cases had an abnormal bowel frequency, a firmer stool consistency and assessed themselves as having abnormal bowel function, predominantly constipation after hysterectomy, than controls. Significantly more cases than controls had consulted a doctor because of constipation but there was no significant difference in laxative usage. There was a significant short-term association between decreased bowel frequency and increased urinary frequency after hysterectomy. This became highly significant in those patients who developed chronic symptoms. Oophorectomy, unilateral or bilateral, did not significantly affect bowel habit other than to intensify the change in stool consistency. The hypothesis is discussed that the post-hysterectomy effects on bowel and bladder function may have a common aetiology in a degree of autonomic denervation of both viscera.

Adult

Molecular analysis of the Escherichia coli K5 kps locus: identification and characterization of an inner-membrane capsular polysaccharide transport system.

The complete nucleotide sequence has been determined of a region of the Escherichia coli K5 antigen gene cluster postulated to encode functions for the translocation of capsular polysaccharide across the inner membrane. This revealed two genes, designated kpsM and kpsT, organized in a single transcriptional unit. Analysis of the predicted amino acid sequence of the KpsM and KpsT proteins indicates that they may function as dual components in a polysaccharide export system analogous to the periplasmic binding protein-dependent transport systems of Gram-negative bacteria. We propose that the KpsT protein acts as an energizer, coupling ATP hydrolysis to the transport process mediated by the KpsM protein. Extensive sequence homology between the KpsM and KpsT proteins and the products of the bexB and bexA genes present in the capsulation (cap) locus of Haemophilus influenzae, indicates that a common mechanism for the export of polysaccharide across the inner membrane may exist in these two micro-organisms.

ATP-Binding Cassette Transporters

Use of the pudendo-anal reflex in the treatment of neurogenic faecal incontinence.

An electrical stimulator has been devised to treat neurogenic faecal incontinence caused by pudendal nerve neuropathy and works on the basis of repeated stimulation of the pudendo-anal reflex arc. Although conduction in the pudendo-anal reflex arc may be prolonged, and is so in neurogenic faecal incontinence, it must be shown to be present before the method can be used. This stimulation results in an immediate rise in the pressure in the anal canal and a significant increase in the electromyographic activity of the external anal sphincter. Maintenance of the stimulus over a two month period raised the mean resting pressure significantly in the anal canal and increased the reflex and voluntary responses of the external anal sphincter to coughing and squeezing actions respectively. The length of the sphincter was not affected. There was widening of the mean motor unit potential duration, though this was not significant. The resting electromyogram was enhanced after the course of treatment, indicating greater spontaneous activity in the external sphincter. The changes led to seven of the eight patients studied becoming continent at the end of the treatment.

Adult

Immunohistochemical detection of abnormal cell proliferation in colonic mucosa of subjects with polyps.

Previous studies have shown the presence of increased proliferation in the large bowel epithelium of those at high risk of developing colon cancer. An in vitro technique for labelling large bowel mucosa with the thymidine analogue bromodeoxyuridine (Brdu) was therefore developed and its ability to distinguish differences in mucosal proliferation between subjects with colorectal adenomas and normal controls was assessed. Sigmoid biopsy specimens from 15 subjects with polyps and 15 age and sex matched controls were labelled and the incorporated Brdu visualised with an immunohistochemical technique. Mean labelling index (LI) was significantly higher in those with polyps than in controls. Differences in the pattern of labelling in colonic crypts were compared by the generation of cumulative labelling distributions. Analysis showed a significant expansion of the proliferative compartment in the colon crypts of those with polyps. It is concluded that in vitro labelling with Brdu provides a useful method for the assessment of mucosal proliferation in subjects at high risk of developing colon cancer.

Adult