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Biomedical subjects

N S Williams

Publications and source records attributed to N S Williams.

At least 19 recordsLinked to original sources
PubMed1992

In vitro modulation of haematoporphyrin derivative photodynamic therapy on colorectal carcinoma multicellular spheroids by verapamil.

Photodynamic therapy has possible applications in the treatment of colorectal carcinoma. The photosensitizer haematoporphyrin derivative (HpD) is selectively retained by tumours. Agents which block p-glycoprotein, an export protein expressed to increased levels in a high proportion of colorectal carcinomas, may modulate photodynamic therapy by reducing HpD efflux from cells. Multicellular spheroids derived from the colorectal cell lines HRT18 and HT29 were incubated for 24 h with 1 microgram ml-1 HpD and 0, 1, 2 and 4 microM verapamil. Bioactivity demonstrated a dose-dependent potentiation of HpD-photodynamic therapy growth retardation. Clonogenic survival of cells disaggregated from spheroids treated with HpD-photodynamic therapy was reduced when spheroids were coincubated with verapamil. The mean(s.e.m.) efflux of HpD from spheroids into fresh medium assessed by fluorimetry was greater in spheroids treated with HpD alone (93.2(18.8) arbitrary units ml-1) than in those treated with verapamil (18.1(2.8) arbitrary units ml-1), P = 0.003. Flow cytometry demonstrated increased HpD fluorescence in cells derived from spheroids coincubated with verapamil over a range of HpD incubation concentrations. Verapamil can potentiate the bioactivity of HpD-photodynamic therapy and HpD may be a substrate for p-glycoprotein.

Colorectal Neoplasms↗
PubMed1992

Accurate method to measure the percentage hepatic replacement by tumour and its use in prognosis of patients with advanced colorectal cancer.

The natural history of patients with colorectal hepatic metastases was studied following resection of the primary tumour. Patients were stratified according to the presence of extrahepatic disease and the percentage hepatic replacement (PHR) measured by planimetry of computed tomographic images. The median(semi-interquartile range (s.i.r.)) PHR of patients without extrahepatic disease was 15.0(10.5) and for those with extrahepatic disease 5.4(2.2) (P less than 0.02). The median(s.i.r.) PHR of all patients was 8.7(8.5). The median(s.i.r.) survival of all patients was 125(85.5) days, 92(114) days for patients with extrahepatic disease and 175(133.5) days for patients with disease confined to the liver (P less than 0.02). A linear correlation between the natural logarithm of PHR and survival was demonstrated (p = -0.76, P less than 0.001) for patients without extrahepatic disease. Extrahepatic disease in patients with colorectal hepatic metastases is a major determinant of survival; PHR has a direct association when extrahepatic disease is absent.

Aged↗
PubMed1992

Evidence from dynamic integrated proctography to redefine anismus.

The role of anismus in the aetiology of defective rectal evacuation was investigated by dynamic integrated proctography in 20 controls and 71 constipated patients. Normal parameters were defined and compared between 21 constipated patients with poor evacuation during proctography (< 40 per cent of contrast evacuated; group 1) and 50 who evacuated fully (> 90 per cent of contrast evacuated; group 2). Nine patients in group 1 failed to evacuate. Radiological abnormalities of the rectum were recorded in all groups but obstructed evacuation was not observed. Anismus (defined as a recruitment of puborectalis electromyogram (EMG) activity of > 50 per cent) was significantly more common in group 1 than group 2 patients (14 of 21 versus 12 of 50, P < 0.01) and present in seven of those unable to evacuate. Eight patients in group 1 failed to raise intrarectal pressure > 50 cmH2O compared with two in group 2 (P < 0.001). Six patients in group 1 demonstrated both anismus and inability to raise intrarectal pressure, which may combine to cause defective evacuation. EMG recruitment alone is insufficient to diagnose anismus. Definition should be based on three criteria: demonstration of puborectalis EMG recruitment of > 50 per cent; evidence of an adequate level of intrarectal pressure (> 50 cmH2O) on straining; and presence of defective evacuation.

Aged↗
PubMed1992

The role and technique of ambulatory anal manometry.

Static anal manometry has proved itself a reliable, reproducible and objective assessment of sphincter function in the investigation of disorders of defecation and continence. Despite this, it gives only very limited information on sphincter function due to the unphysiological nature of its measurement. Technical advances, particularly in digital data storage, have made the recording of anal pressure in a normal environment for prolonged periods of time possible. This offers an improved understanding both of anal activity and the interaction of rectal and anal function in normal and pathological states. In normal subjects anal function during a number of normal physiological events such as micturition, passage of flatus and sleep have been investigated. The sampling reflex has been further defined. Abnormalities of the sampling reflex, rectal activity and slow wave activity in the anal sphincter have been demonstrated in a number of pathological conditions of the anorectum and in the states of incontinence or constipation. Effective ambulatory anal manometry remains in its infancy. With continuing advances it offers exciting possibilities in defining normal or abnormal activity of the anorectum and in the investigation of patients with disorders of defecation and continence.

Anal Canal↗
PubMed1992

Hemodynamic effects of central angiotensin I, II, and III in conscious rabbits.

We have examined the hemodynamic effects of intraventricular angiotensins in conscious rabbits. Fourth ventricular injections of angiotensin II (ANG II, 8 fmol to 25 pmol) produced dose-dependent pressor responses at doses 400 times less than equipressor intravenous doses. Lateral ventricle administration of doses up to 1,000 pmol had little effect on mean arterial pressure (maximum +7 +/- 3 mmHg, P < 0.05, n = 9). Comparison of dose-response curves to ANG I, II, and III showed that all three had similar maximum pressor effects (27 +/- 3 mmHg), with ANG I being four times less potent than ANG II, and ANG III as potent as ANG II. Central pretreatment with the ANG-converting enzyme inhibitor enalapril abolished the pressor response to ANG I, suggesting that it was mediated entirely through ANG II. Examination of the hemodynamic changes after ANG I, II, and III in rabbits instrumented with aortic, mesenteric, or hindquarter flow probes showed that the rise in blood pressure to all three agents was due entirely to a decrease in total peripheral conductance, since cardiac output and heart rate fell. Peripheral conductance changes were not uniform, with the mesenteric bed showing an average 20 +/- 3% fall in conductance, while the hindquarter conductance increased (+12 +/- 3%). In sinoaortic-denervated rabbits, however, central angiotensins reduced conductance equally in the hindlimb and mesenteric beds, suggesting that the hindlimb dilatation in the baroreceptor intact rabbit was due to baroreflex buffering of the pressor effect. In conclusion, these studies suggest that the main sites for ANG effects on the cardiovascular system are located in the brain stem.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin I↗
PubMed1991

Development of an electrically stimulated neoanal sphincter.

In early surgical attempts to create a neoanal sphincter for patients who are faecally incontinent, skeletal muscle (usually the gracilis) has been transposed around the anal canal. Despite modifications, such as intermittent electrical stimulation, this procedure is likely to fail because the fast-twitch gracilis muscle is incapable of prolonged contraction without fatigue. Long-term electrical stimulation to convert such a muscle to a slow-twitch, fatigue-resistant muscle, though practicable, has yielded inconsistent results. We describe further modifications of this technique. A neoanal sphincter was constructed with an electrically stimulated transposed gracilis muscle in 20 incontinent patients with a deficient anal sphincter, and as part of a reconstruction in 12 patients in whom the anorectum had been excised or was congenitally absent. A totally implanted stimulator was used to convert the muscle from a fast-twitch to a slow-twitch muscle. Other modifications included vascular delay 4-6 weeks before transposition of the muscle, stimulation of the main nerve to the gracilis rather than its peripheral branches, and intermittent higher frequency stimulation. 2-4 of these modifications gave significantly fewer failures than did 0-1. With the new technique, continence has been restored in patients whose only other treatment option was a permanent stoma.

Adolescent↗
PubMed1990

Electrically stimulated sartorius neosphincter: canine model of activation and skeletal muscle transformation.

The sartorius muscle was transposed into the abdominal cavity of six dogs, passed around a Thiry-Vella loop and sutured to itself to form a neosphincter. The muscle was activated by electrical stimulation and on contraction the neosphincter stopped or reduced the flow of saline through the Thiry-Vella loop in all animals until the onset of muscle fatigue. Continuous low frequency stimulation was used to transform the skeletal muscle, and when studied after a mean of 8 weeks of stimulation (range 6-11 weeks) the neosphincter stopped the flow for a significantly longer period of time (P = 0.027). Associated with the improved neosphincter function was a significant decrease in the fusion frequency (P = 0.003) and prolongation of the stimulus-peak tension time as assessed by a strain gauge sutured to the neosphincter muscle (P = 0.002). The changes in the contraction properties of the skeletal muscle suggest that continuous low frequency stimulation transformed the muscle fibres from type 2 to type 1, resulting in improved fatigue resistance and potential for continuous sphincter activity.

Animals↗
PubMed1990

Prolonged anorectal manometry and external anal sphincter electromyography in ambulant human subjects.

We have developed a method for prolonged combined anorectal manometry and electromyography (EMG) of the external anal sphincter in ambulant subjects. Fourteen healthy volunteers were studied for a total of 284 hr (mean of 20.3 hr/subject). Anorectal manometry was performed using a probe with twin pressure sensors. EMG was recorded by one indifferent and two differential silver-silver chloride surface electrodes positioned 0.5-0.75 cm from the anus on either side. The sampling reflex occurred frequently and was significantly (P less than 0.001) more common during wakefulness than during sleep and also following meals than during fasting (P less than 0.01). The passage of flatus was associated with transient relaxation of the anal canal in 19% of episodes. In contrast, there was a contractile episode with no preceding relaxation in 75% of episodes. The anal sphincter had significantly (P less than 0.05) more action potentials (APs) during the day (12.8 +/- 3.2 APs/10 min) than at night (1.6 +/- 1.3 APs/10 min). During micturition, anal canal pressure rose (mean 15 mm Hg) in association with powerful external anal sphincter contractions. Our data show that, normally, contractile activity both in the anal canal and external anal sphincter maintains fecal continence during micturition and the passage of flatus. The technique should lead to a better understanding of the normal mechanisms of fecal continence during waking and sleep and of the pathophysiology of disorders of anorectal function.

Action Potentials↗
PubMed1990

Restoration of gastrointestinal continuity and continence after abdominoperineal excision of the rectum using an electrically stimulated neoanal sphincter.

A new operation is described in which a neorectum and neoanal sphincter mechanism have been constructed to restore gastrointestinal continuity and continence in a patient who required abdominoperineal excision of the rectum for a low rectal cancer. The neorectum was constructed by bringing colon down into the pelvis and anastomosing it to the perineal skin. The neoanal sphincter was fashioned from a transposed gracilis muscle and was activated electrically by a totally implanted stimulator. A period of chronic low-frequency stimulation altered the muscle characteristics and enabled the neosphincter to contract continually without fatigue. The patient was continent when the stimulator was turned on and was able to void when the stimulator was turned off.

Abdomen↗
PubMed1990

Evidence for motor neuropathy and reduced filling of the rectum in chronic intractable constipation.

Subtotal colectomy with ileorectal anastomosis is now frequently offered to patients with slow transit constipation who have severe symptoms and no response to more conventional medical treatment. If this operation is to be successful, the underlying problem should be delay in the progress of contents through the colon but no mechanical or functional obstruction in the small bowel or rectum. We have used a recently described technique of prolonged ambulant manometry and electromyography to investigate anorectal function in these patients. Pressure data were collected using a 2 mm diameter intrarectal probe carrying microtransducers, and external anal sphincter activity was assessed by a pair of silver-silver chloride surface electrodes. Fourteen control subjects and eight patients with colonic inertia were studied. Sampling reflexes, indicative of rectal filling, occurred at mean (SEM) rates of 7.4 (2.0)/hour in controls but were significantly reduced in patients (2.4 (0.3)/hour (p less than 0.01]. Recurrent rectal motor complexes were seen to occur in both groups at intervals of 76 (1.8) minutes in controls and 64.9 (7.2) minutes in patients (p less than 0.1), and with amplitudes of 42.4 (2.1) mmHg and 9.2 (0.7) mmHg (p less than 0.001), respectively. External sphincter electromyographic spike activity did not differ between groups. Our results support the concept of reduced transit of faeces to the rectum from the colon over a 24 hour period in slow transit constipation and suggest that a motor neuropathy may also be present in the rectum.

Adult↗
PubMed1989

Comparison of digital and manometric assessment of anal sphincter function.

Anal sphincter function was assessed by digital examination and anal canal manometry in 66 patients and controls. Digital scores were allotted by using visual analogue scales for basal and squeeze sphincter function and were compared with the corresponding pressures. There were good correlations between digital basal score and maximum basal pressure (Spearman rank correlation coefficient rs = 0.56, P less than 0.001), and digital squeeze score and maximum squeeze pressure (rs = 0.72, P less than 0.001). There were wide ranges of sphincter function on digital and manometric assessment with considerable overlap between patient groups. Digital scores detected differences in sphincter function between patient groups as accurately as manometry. The sensitivities and specificities of digital scores and anal canal manometry in segregating continent and incontinent patients were similar. It was concluded that digital estimation was equally as good as assessment of anal sphincter function as anal canal manometry.

Adult↗