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Biomedical subjects

W M Sun

Publications and source records attributed to W M Sun.

At least 19 recordsLinked to original sources
PubMed1995

Anorectal function in patients with complete spinal transection before and after sacral posterior rhizotomy.

BACKGROUND/AIMS: The implantation of spinal stimulators to facilitate defecation in patients with complete spinal transection involves division of the posterior sacral nerve roots. The aim of this study was to investigate the role of spinal reflexes in anorectal function. METHODS: Anorectal manometry and electromyography were performed in 14 patients with supraconal spinal cord transection (C6-T12) before and after complete sacral posterior rhizotomy and in 30 normal controls. RESULTS: Patients with spinal transection lost conscious control of the external anal sphincter. Reflex responses to intra-abdominal pressure and to rectal distention were eliminated after rhizotomy, indicating that they are spinal reflexes. Rhizotomy also eliminated giant rectal contractions induced by rectal distention in these patients. In contrast, the exaggerated sphincter relaxation induced by rectal distention was not influenced by rhizotomy. Discriminant rectal sensation was lost, but patients with thoracic cord lesions perceived a dull pelvic sensation during rectal distention even after rhizotomy. CONCLUSIONS: The exaggerated anorectal smooth muscle responses and absent conscious control of the anorectum may explain why patients with complete spinal transection experience uncontrollable reflex defecation, and the persistence of external anal sphincter contraction during straining may impair fecal expulsion. The elimination of these responses after posterior rhizotomy prevented reflex defecation while facilitating manual evacuation.

Adult↗
PubMed1995

Relationship between fractional calcium absorption and gastric emptying.

The relationship between calcium absorption and gastric emptying and the precision of measurement of fractional calcium absorption using a single isotope technique were evaluated in 14 normal postmenopausal women (age range 61-72 years). On two occasions separated by between 5 and 15 days, each subject was given 250 mL water containing 0.2 MBq of 45Ca in 20 mg of calcium carrier as the chloride, 20 mg kg-1 paracetamol and 9 MBq of 99mTc sulphur colloid. Venous blood samples were taken at -2, 15, 30, 45, 60, 90, 120, 150 and 180 min after consumption of the drink, and gastric emptying (GE) was monitored with a gamma camera. Fractional calcium absorption in the first hour (alpha 6) was calculated from the blood samples obtained at 15, 30, 45, 60, 90 and 120 min. An absorption rate was also derived from the 60 min sample using only a calibration curve (alpha 1). There were close correlations between radiocalcium absorption on the two study days (r = 0.89, P < 0.001 for both alpha 1 and alpha 6) and between alpha 1 and alpha 6 (r = 0.93, P < 0.001). Plasma paracetamol concentrations at 15 min were directly related to the early phase of GE (r = 0.42, P < 0.05). In contrast, calcium absorption was inversely related to GE (r = 0.45, P < 0.05). We conclude that radiocalcium absorption is not greatly influenced by gastric emptying rate and that the single blood sample procedure has similar precision to the six-blood sample test.

Acetaminophen↗
PubMed1995

Effect of drink temperature on antropyloroduodenal motility and gastric electrical activity in humans.

There is little information on the motor mechanisms underlying the effects of meal temperature on gastric emptying. The effects on antropyloric pressures and the surface electrogastrogram of ingesting drinks at 4 degrees C, 37 degrees C, and 50 degrees C (350 ml normal saline and 50 ml low calorie (7 kj) orange cordial) given in randomised order were measured over 60 minutes in 12 normal volunteers (10 men and 2 women, aged 18-55 years). The warm and cold drinks suppressed antral pressure waves (p < 0.05), altered the organisation of antropyloric pressure waves (p < 0.05), stimulated isolated pyloric pressure waves (p < 0.05), and increased electrogastrogram frequency (p < 0.05) when compared with the 37 degrees C drink. These changes were greatest in the first 30 minutes after ingestion and greater (p < 0.05) with the 4 degrees C drink. Temperature has major effects on postprandial antropyloroduodenal motility in normal subjects. Both cold and warm drinks stimulate a pattern of motility associated with retardation of transpyloric flow.

Adolescent↗
PubMed1995

Gastric emptying of oil and aqueous meal components in pancreatic insufficiency: effects of posture and on appetite.

The aims of this study were to evaluate the effects of posture on gastric emptying, intragastric distribution, and satiation after a meal containing oil and aqueous phases in patients with exocrine pancreatic insufficiency. Five patients with cystic fibrosis (CF) consumed 60 ml 99mTc-labeled (V)-thiocyanate olive oil and 290 ml 113mIn-labeled diethylenetriaminepentaacetic acid soup while sitting and while lying in the left lateral decubitus position. Hunger and fullness before and after the meal were recorded. Results were compared with those obtained in 11 normal volunteers. In both postures emptying of oil was faster (P < 0.01) in CF patients. Emptying of the aqueous phase was faster (P < 0.01) in CF patients in the decubitus position. In normal subjects there was no overall difference in emptying of oil between the two postures, whereas emptying of the aqueous phase was delayed (P < 0.01) in the decubitus position. In CF patients emptying of oil was faster (P < 0.01) in the decubitus position, and emptying of the aqueous phase was only slightly faster (P < 0.05) in the sitting position. For both postures there was greater retention (P < 0.05) of oil in the proximal stomach in normal subjects than CF patients. Hunger decreased (P < 0.05) after the meal in the control subjects, but there was no change in CF patients. These results indicate that in CF patients with pancreatic exocrine insufficiency 1) gastric emptying of nonhomogenized fat is faster than normal, 2) gravity affects gastric emptying of oil, and 3) effects of a fatty meal on hunger are reduced.

Adult↗
PubMed1995

Pharmacokinetic considerations in gastrointestinal motor disorders.

Although it has been recognised that alterations in gastrointestinal motility, whether induced by physiological or pathological processes, have significant effects on the pharmacokinetics of orally administered drugs, this subject has received inappropriately little attention. Studies relating to this topic have focused on healthy volunteers and animals and have largely been confined to the effects of single drug doses. There is limited information about the effects of disease on pharmacokinetics under steady-state conditions. Changes in gastrointestinal motility may affect the pharmacokinetics of orally administered drugs by altering the rate of delivery, bioavailability or mucosal absorption of the drug. In general the rate of absorption and time taken to achieve maximal plasma concentrations for well absorbed drugs may be modified by changes in gastrointestinal motility, but overall bioavailability is not usually affected. In these cases the therapeutic and clinical effects of the alteration in pharmacokinetics will, therefore, depend on which parameters are important for the action of the drug. For poorly absorbed drugs both the rate of absorption and bioavailability are likely to be altered by changes in gastrointestinal motility. However, the complex effects of food and disease, as well as the properties and formulation of any drug (solubility, ease of dispersion, delayed release formulation) often make the prediction of the magnitude, or even the direction, of any effect difficult to predict. Drugs with direct effects on gastrointestinal motility may influence their own patterns of absorption. In patients with gastrointestinal motility disorders, drugs administered in a controlled release formulation, or those with poor bioavailability, are most likely to have a poorly predictable therapeutic effect. Care should be taken to ensure that the formulation of the drug, its timing of administration in relation to meals and the use of coadministered drugs optimise, or at least ensure consistent absorption.

Administration, Oral↗
PubMed1995

Bidirectional glutathione transport by cultured human retinal pigment epithelial cells.

PURPOSE: To characterize glutathione (GSH) transport by cultured human retinal pigment epithelial (HRPE) cells. METHODS: Cultured HRPE cells were pretreated with acivicin for GSH efflux and with buthionine sulfoximine for GSH uptake to prevent the breakdown and resynthesis of GSH. Efflux was measured by the linear rate of accumulation of GSH in the supernatant; uptake was measured using [35S] GSH plus varying concentrations of GSH. Molecular forms were verified by high-performance liquid chromatography. HRPE cell mRNA was probed for the presence of the two recently cloned rat sinusoidal and canalicular GSH transporters, (RsGshT and RcGshT), by Northern blot analysis. RESULTS: Glutathione efflux was temperature dependent (undetectable at 4 degrees C), and its averaged 23 +/- 3.3 pmol/10(6) cells/minute or 10% of the total GSH effluxed per hour (total cell GSH = 13.6 +/- 1.5 nmol/10(6) cells). Efflux was not influenced by dithiothreitol or sulfobromophthalein-reduced GSH adduct, agents known to affect liver sinusoidal GSH transport. Glutathione uptake was linear up to 45 minutes and was temperature dependent. The difference between 37 degrees C and 4 degrees C uptake values represented true uptake. Glutathione uptake (2 microCi/ml + 1 mM mass) was Na independent and was inhibited significantly by phenol-3,6-dibromphthalein disulfonate. The kinetics of GSH uptake was assessed by measuring uptake with 35S-GSH and 0.05 to 40 mM extracellular GSH for 30 minutes. Uptake was saturable with Vmax = 18.7 +/- 1.7 nmol/10(6) cells/30 minutes, Km = 12.1 +/- 1.9 mM, n (binding site) = 1. On Northern blot analysis, HRPE cells express mRNA for RcGshT but not for RsGshT. CONCLUSIONS: The similarities in functional characteristics of GSH transport and the presence of RcGshT-like mRNA suggest GSH transport in HRPE cells is mediated by a RcGshT homolog. Although the transporter can operate bidirectionally, it is expected to be a net efflux pump under normal physiologic conditions because the intracellular GSH concentration is much higher.

Biological Transport↗
PubMed1995

Hormonal and cell density regulation of hepatic gamma-glutamylcysteine synthetase gene expression.

We previously reported that the activity of gamma-glutamylcysteine synthetase (GCS), the rate-limiting enzyme in GSH synthesis, is under both hormonal and cell density regulation in cultured rat hepatocytes. Specifically, the addition of insulin or hydrocortisone to culture media or the lowering of the initial plating cell density increased cell GSH by increasing the activity of GCS. In the present study, we examined the molecular mechanism of these effects. To determine whether the increase in GCS activity is associated with an increase in GCS heavy subunit (GCS-HS) mRNA expression, the steady state mRNA levels of GCS-HS were examined with the use of Northern blots. After 24-hr treatment of high density (0.6 x 10(5) cells/cm2) cultured rat hepatocytes with insulin (1 micrograms/ml) or hydrocortisone (50 nM), the steady state GCS-HS mRNA level increased by approximately 1-2 fold. When the plating density was decreased to 0.1 x 10(5) cells/cm2, the steady state GCS-HS mRNA level also increased by 1-2 fold 24 hr later. An increase in the steady state GCS-HS mRNA level was found within 4 hr of either hormonal treatment or cell density manipulation. The increase in steady state GCS-HS mRNA level resulted from increased gene transcription, as the transcriptional rates of GCS-HS after hormonal or cell density manipulation were increased by 2-3-fold, whereas the rates of GCS-HS mRNA degradation remained unchanged. Western blotting confirmed the increase in GCS-HS protein level after hormone treatment or lowering of plating cell density. When examined in vivo, the steady state GCS-HS mRNA level decreased by 50% in a rat in which diabetes had been induced with streptozotocin for 1 week; this was prevented with insulin replacement. In summary, GCS-HS gene expression is under both hormonal and cell density regulation.

Amino Acid Sequence↗
PubMed1994

Ozone, NO, and NO2: oxidant air pollutants and more.

This article reviews the acute and chronic toxicity of the three oxidant air pollutants ozone, nitric oxide (NO), and nitrogen dioxide (NO2). The toxicity of binary mixtures of NO2 with other inhaled agents is also discussed. Newer studies are emphasized, especially those published in the last 5 years or still in press. Very recent data from our laboratory that suggest a new cellular mechanism of importance in lung injury in animals exposed to mixtures of ozone and NO2 that may have general relevance with regard to the effects of oxidant air pollutants on the lung are also presented.

Air Pollutants↗
PubMed1992

Haemorrhoids are associated not with hypertrophy of the internal anal sphincter, but with hypertension of the anal cushions.

A combined manometric and ultrasonographic study of the internal anal sphincter was carried out in 20 patients with haemorrhoids and 20 age-matched normal controls. Mean(s.e.m.) basal anal pressure was significantly higher in patients than in controls, 62(4) versus 45(6) cmH2O (P less than 0.05), although there were no significant differences in mean maximum basal and squeeze pressures. During rectal distension 90 per cent of patients showed no reduction in anal pressure in the outermost anal channel, although the internal sphincter electromyogram was suppressed and the external sphincter electromyogram did not necessarily increase above baseline. The mean(s.e.m.) maximum residual pressure was significantly higher in patients, 70(6) versus 45(6) cmH2O (P less than 0.05). Direct pressure measurement in anal cushions exhibited abnormally high median pressure in patients compared with controls, 35 versus 10 cmH2O (P less than 0.001). Pressures recorded during coughing and straining were also significantly higher in patients than in controls (P less than 0.001). Ultrasonographic study of the anal canal revealed a clear image of the internal sphincter, the thickness of which could easily be measured. The mean(s.e.m.) thickness of the sphincter was not significantly different, 2.3(0.2) versus 2.1(0.1) mm, between patients with haemorrhoids and controls (P = 0.18). The absence of any significant differences in the internal sphincter thickness between normal subjects and patients with haemorrhoids suggests that the high anal pressure in patients with haemorrhoids is of vascular origin.

Adult↗
PubMed1992

Anorectal function in patients with complete supraconal spinal cord lesions.

Anorectal manometry and sphincter electromyography were performed in 23 patients with complete supraconal traumatic spinal injuries and 30 age and sex matched control subjects. Basal pressures in the spinal group were similar to those in normal subjects but conscious control of sphincter activity was abolished in all spinal patients. Discriminant rectal sensation was also abolished during rectal distension, but 40% of patients experienced a dull pelvic ache at maximum levels of distension. Phasic rectal contraction and anal relaxation were present but exaggerated and induced at lower distending volumes than in normal subjects. The configuration of the rectal pressure/volume relationship was linear in patients compared with a reversed 'S' shape in normal subjects. The external anal sphincter response to rectal distension was noticeably attenuated, reinforcing the view that this spinal reflex is heavily modulated by supraspinal centres under normal circumstances. The external anal sphincter response to increases in abdominal pressure was also attenuated, and the anal pressures were strongly correlated with the level of the lesion and the abdominal pressure the patient could generate. No spinal patient showed a decrease in external anal sphincter activity during straining 'as if to defecate.' The exaggerated anorectal smooth muscle responses to rectal distension and the attenuated external sphincter response explain why patients with complete supraconal spinal lesions experience uncontrollable reflex defecation, while the persistance of external and sphincter contraction and the absence of any external anal sphincter relaxation during straining 'as if to defecate' might explain the difficulty that these patients have in consciously expelling rectal contents.

Adolescent↗
PubMed1992

Utility of a combined test of anorectal manometry, electromyography, and sensation in determining the mechanism of 'idiopathic' faecal incontinence.

Combined tests of anorectal manometry, sphincter electromyography and rectal sensation were carried out in 302 patients with faecal incontinence (235 women, 67 men). The results obtained were compared with 65 normal subjects (35 women, 30 men). A mechanism for incontinence was identified in all and the majority of patients had more than one abnormality. Two hundred and seventy eight patients (92%) had a weak external anal sphincter, 185 of these (67%, mostly women) also showed abnormal perineal descent, and 14 women showed clinical evidence of sphincter damage as a result of obstetric trauma. Ten per cent of patients with impaired external anal sphincter contraction showed associated evidence of spinal disease (impaired rectal sensation plus attenuated or enhanced reflex external anal sphincter activity). Unlike the other groups, the 'spinal' group contained equal numbers of men and women. Ninety seven patients (32%) had evidence of a weak internal anal sphincter. The external sphincter was also very weak and 92% of these patients also had perineal descent. Eighty two patients (27%) showed an unstable internal sphincter, characterised by prolonged 'spontaneous' anal relaxation under resting conditions and an abnormal reduction in anal pressure after conscious contraction of the sphincter or an increase in intraabdominal pressure. One hundred and forty two patients (47%) had a hypersensitive rectum associated with enhanced anorectal responses to rectal distension. All these patients had an abnormally weak external sphincter, suggesting that the hypersensitive or 'irritable' rectum should not be regarded as a cause of faecal incontinence unless accompanied by external sphincter weakness. Twenty four patients (8%) showed a normal basal and squeeze pressures and impaired rectal sensation; six showed giant rectal contractions during rectal distension. The results show that idiopathic faecal incontinence is not caused by a single abnormality, and it is suggested that combined anorectal manometry, electromyography, and sensory testing is a useful technique to identify the causes of faecal incontinence and provide a basis for appropriate treatment.

Adolescent↗
PubMed1991

Reflex anal dilatation: effect of parting the buttocks on anal function in normal subjects and patients with anorectal and spinal disease.

Anal dilatation in response to gentle parting of the buttocks has been advocated as a sign of sexual abuse in children, but nothing is known of the physiology of this response or its existence in normal subjects, in patients with spinal disease, and in patients with a weak sphincter and whether it can be elicited after training. To answer these questions we investigated the effect of parting the buttocks on anal function. Combined anal manometry and electromyography was conducted in six normal subjects (five men, one woman, aged 19-53 years), in 18 patients with faecal incontinence (three men, 15 women, aged 30-80 years), and in seven paraplegic patients (six men, one woman, aged 25-36 years), in four of whom the posterior sacral roots had been cut. Parting the buttocks in normal subjects reduced the pressure in the anal canal from 102 (20) to 14 (3) cm H2O (mean (SEM), p less than 0.00001), but did not cause the anus to gape. This drop in pressure was associated with increased electrical activity in the external anal sphincter. Normal subjects could consciously relax the external anal sphincter and reduce the anal pressure but not so as to result in anal gaping during traction on the buttocks, even after anal dilatation. Stimulation of the anal lining by moving a probe in and out of the anal canal increased the activity of the external anal sphincter, raising anal pressures. Paraplegic patients who had lost conscious control of their external sphincters showed anal gaping when the buttocks were parted. A similar phenomenon was seen in patients with faecal incontinence who had weakness of the external anal sphincter, while incontinent patients with weakness of both sphincters showed anal gaping even at rest. Inasmuch as the results of our study can be applied to children, the data suggest that reflex anal dilatation should only be used to support a diagnosis of sexual abuse if sphincter function is otherwise normal and there is no evidence of cerebrospinal disease. Although our results do not support the notion that children could become so conditioned to repeated digital or penile penetration of the anus that they can cause the anus to gape when the buttocks are parted, neither do they exclude it.

Adult↗
PubMed1990

Control of defecation in patients with spinal injuries by stimulation of sacral anterior nerve roots.

OBJECTIVE: To observe the effects of stimulation of the sacral anterior roots on anorectal and low colonic pressures and to programme implanted stimulators to produce defecation. DESIGN: Prospective study of 12 consecutive patients. SETTING: Spinal injuries unit and university gastrointestinal physiology department. PATIENTS: 12 Patients with complete supraconal spinal cord lesions. Their injuries had been sustained at least two years before the study. INTERVENTIONS: A Brindley-Finetech intradural sacral anterior root stimulator was implanted in all patients. Three months postoperatively the stimulator settings were adjusted after measurement of simultaneous anorectal and low colonic pressures. MAIN OUTCOME MEASURES: Full defecation. RESULTS: Six patients achieved complete rectal evacuation of faeces using the implant and subsequently did not require manual help for defecation. For all but one of the patients the total time taken to complete defecation was reduced, and all were free from constipation, the most prevalent gastrointestinal symptom in patients with spinal injuries. CONCLUSIONS: Sacral anterior root stimulators can be programmed to achieve complete unassisted defecation and can considerably improve the quality of life of patients with spinal injuries.

Adult↗
PubMed1990

Hypertensive anal cushions as a cause of the high anal canal pressures in patients with haemorrhoids.

Anorectal manometry and electrophysiology studies were conducted in 25 men with non-prolapsing haemorrhoids, ten men with prolapsing haemorrhoids, and 20 age-matched normal men. Mean(s.e.m.) minimum basal pressures were significantly higher in patients with non-prolapsing haemorrhoids than in normals (61(5) versus 43(7) cmH2O; P less than 0.05) or patients with prolapsing haemorrhoids (55(4) cmH2O; P less than 0.05). There were no significant differences in maximum basal pressures and maximum squeeze pressures. During rectal distension, all normal subjects showed relaxation in all anal channels. However, 92 per cent of patients with non-prolapsing haemorrhoids and 40 per cent of patients with prolapsing haemorrhoids showed no relaxation in the outer anal channels, even when relaxation occurred in the inner anal channels; internal sphincter electrical slow waves were suppressed and the integrated electrical activity of the external sphincter had returned to predistension values. Maximum residual anal pressures during balloon distension were significantly higher in patients with non-prolapsing haemorrhoids than normals (75(7) versus 45(7) cmH2O; P less than 0.01), or patients with prolapsing haemorrhoids (53(3) cmH2O; P less than 0.05). When subjects increased intra-abdominal pressure rectal pressure was significantly higher in patients with non-prolapsing haemorrhoids than in normal subjects (157(10) versus 105(15) cmH2O; P less than 0.05), but not in patients with prolapsing haemorrhoids (126(14) cmH2O). Resting anal cushion pressures in patients with non-prolapsing or prolapsing haemorrhoids were much higher than normal capillary or venous pressure and significantly higher than those recorded in normals (median 35, 35 versus 10 cmH2O; P less than 0.0001). Pressures recorded during coughing (60, 60 versus 30 cmH2O) and straining (78, 80 versus 55 cmH2O) were also significantly higher (P less than 0.0001) in patients than in normals. Pressures after straining were higher than those recorded before (38 versus 29 cmH2O; P less than 0.05) in 60 per cent of patients but no normal subjects and took 18-36 s to return to baseline. This study suggests that the abnormally high pressures in the anal canal in patients with haemorrhoids may be related to an increased vascular pressure in the anal cushions.

Action Potentials↗
PubMed1990

The role of transient internal sphincter relaxation in faecal incontinence?

Twenty-five (18%) of 140 incontinent patients and 6 (17%) of 35 normal controls showed episodes of spontaneous internal sphincter relaxation during 30 min multiport manometric and electromyographic recording under resting conditions. The episodes lasted at least 15 s and reduced the pressure in the outermost anal channels by at least 20 cm of water. Patients exhibited more episodes of relaxation than controls (4.3 +/- 0.6 vs 2.3 +/- 0.2 per subject; mean +/- SEM; p less than 0.05) and the pressures fell to lower values (19 +/- 1 vs 42 +/- 5 cm water, p less than 0.01), but the duration of relaxation was not significantly different (53 +/- 4 vs 40 +/- 7 s). Episodes of spontaneous relaxation were associated with simultaneous rectal contractions in 33% of the normal subjects and 45% of incontinent patients. Unlike normal subjects, most of the episodes of transient relaxation recorded in the incontinent group were not associated with compensatory increases in the electrical activity of the external anal sphincter (77% vs 17%; p less than 0.05). Over 50% of the incontinent patients who showed spontaneous relaxation also showed post squeeze or post-strain IAS relaxations whereas these were seen in less than 6% of the normal subjects with spontaneous relaxation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Effect of oral nicardipine on anorectal function in normal human volunteers and patients with irritable bowel syndrome.

Paired controlled studies were performed in 10 normal volunteers and 32 patients with irritable bowel syndrome to investigate the effect of the calcium channel blocker nicardipine, on the responses of the anorectum to rectal distension and a meal. Nicardipine was administered orally in standard (20 mg) and sustained-release (30 mg twice a day) formulations. In normal volunteers standard nicardipine had no significant effect on the rectal responses to distension but did significantly reduce the postprandial motility index (P less than 0.05). In the patients with irritable bowel syndrome, standard nicardipine caused a significant reduction in distension-induced rectal motor activity (P less than 0.05) and increased the rectal sensory thresholds for desire to defecate and discomfort (P less than 0.02). Slow-release nicardipine caused a significant reduction in distension-induced activity (P less than 0.05) but did not alter rectal sensory thresholds. Both formulations of nicardipine significantly reduced the postprandial motility index (P less than 0.05) and symptoms (P less than 0.05). In conclusion, this study confirms that calcium channel blockers may be useful in the management of irritable bowel syndrome.

Administration, Oral↗