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Biomedical subjects

A Smythe

Publications and source records attributed to A Smythe.

At least 19 recordsLinked to original sources

The effect of photodynamic therapy (PDT) on oesophageal motility and acid clearance in patients with Barrett's oesophagus.

BACKGROUND: Barrett's oesophagus is the major risk factor for oesophageal adenocarcinoma. It is proposed that long-term re-epithelialisation, which has been achieved following ablation using 5-aminolaevulinic acid (5-ALA) photodynamic therapy (PDT) may reduce the risk of malignant change. However, it is not known whether PDT modifies oesophageal motility. AIM: To assess oesophageal pH and motility before and after PDT ablation in treated and untreated areas of the oesophagus. METHODS: Twelve patients (10 male) with Barrett's oesophagus, median segment length 4 cm, were treated with PDT ablation. Twenty-four hours pH assessment and oesophageal manometry were performed before and 4-6 weeks after ablation. PDT was carried out using 635 nm red light, 4-6h after administration of 30 mg/kg 5-ALA. Proximal (untreated) and distal (treated) oesophageal resting pressure, wave amplitude, percentage peristalsis and percentage study time oesophageal pH<4, were assessed. Proton pump inhibitors (PPI) were administered throughout the study. RESULTS: There were no significant differences in oesophageal motility in treated or untreated areas of the oesophagus after PDT compared to pre-treatment values. Patients who continued to experience oesophageal acid exposure required more treatments to achieve complete Barrett's ablation. CONCLUSIONS: Oesophageal motility following ALA-PDT suggests a trend toward enhanced wave propagation however continued oesophageal acid exposure may affect PDT efficacy.

Aged↗

Bethanechol provocation testing does not predict symptom relief after cholecystectomy for acalculous biliary pain.

BACKGROUND: The currently accepted hypothesis to explain acalculous gallbladder pain is the lack of contractile co-ordination between the body and neck. We have previously shown that bethanechol, a muscarinic stimulant causes differential stimulation of these two regions. AIM: To evaluate the reliability of bethanechol-induced gallbladder contraction in predicting symptom relief after cholecystectomy in patients with acalculous gallbladder disease. METHODS: Fifty-one patients underwent a bethanechol provocation test together with serial ultrasound to determine gallbladder emptying. McGill pain questionnaires were completed, and patients positive for pain (bethanechol provocation test +ve) were offered cholecystectomy, and patients negative for pain (bethanechol provocation test -ve) were reassessed at 6 months and offered cholecystectomy if symptoms persisted. All patients answered pain questionnaires either 6 months after surgery or as follow-up. RESULTS: There was no difference in the percentage of gallbladder emptying between the bethanechol provocation test +ve and bethanechol provocation test -ve groups. Fifty-three percent of bethanechol provocation test +ve patients and 54% of bethanechol provocation test -ve patients still remained symptomatic 6 months after surgery. Conclusion. Gallbladder pain provoked by bethanechol does not predict symptom relief after cholecystectomy.

Adult↗

A requiem for the cholecystokinin provocation test?

BACKGROUND: The cholecystokinin provocation test (CCKPT) has been claimed to predict a better symptomatic result after cholecystectomy in patients with acalculous biliary pain. AIMS: To examine the predictive value of the CCKPT for symptom relief after cholecystectomy in both CCKPT positive and negative patients. PATIENTS AND METHODS: Fifty eight patients with acalculous biliary pain underwent CCKPT with serial ultrasound gall bladder volumetry. CCKPT positive patients were offered cholecystectomy; negative patients were reassessed and were offered a cholecystectomy if symptoms persisted. Six months after cholecystectomy, the CCKPT was repeated. RESULTS: Of 32 CCKPT positive patients, 27 underwent cholecystectomy and of these, 18 (67%) became symptom-free. Postoperatively, 20 of 25 patients converted to CCKPT negative but five remained CCKPT positive and were symptomatic. Of the 26 CCKPT negative patients, nine became symptom-free without cholecystectomy; six of 14 (42.8%) patients undergoing cholecystectomy became asymptomatic and remained CCKPT negative. Cholecystectomy seemed to reduce symptoms in both groups, but there was no significant difference in the symptomatic outcome between preoperative CCKPT positive and negative patients. CONCLUSIONS: In this study, cholecystokinin provocation testing did not predict symptomatic benefit from cholecystectomy and we suggest it should no longer be used in the evaluation of patients with acalculous biliary pain.

Adolescent↗

A recombinant GM-CSF-PE40 ligand toxin is functionally active but not cytotoxic to cells.

A granulocyte/macrophage colony-stimulating factor (GM-CSF)-Pseudomonas exotoxin (PE) 40 fusion protein was constructed for potential use in the treatment of myeloid leukaemias, as a conditioning agent prior to allogeneic bone marrow transplantation or for ex vivo purging of malignant cells prior to autologous bone marrow transplantation. The GM-CSF-PE40 fusion protein successfully binds to the GM-CSF receptor and is capable of initiating a mitogenic signal similar to native GM-CSF in the GM-CSF-dependent TF1 cell line. The toxin component also appears to be fully functional as determined by an in vitro adenosine diphosphate-ribosylation assay. The GM-CSF-PE40 fusion protein, however, was not cytotoxic to a number of myeloid leukaemia cell lines. It is suggested that the mechanism of internalization of the GM-CSF receptor is not appropriate for the translocation of PE to the cytosol where it can fulfil its cytotoxic potential.

ADP Ribose Transferases↗

Effect of cisapride on oesophageal motility and duodenogastro-oesophageal reflux in patients with Barrett's oesophagus.

OBJECTIVE: Both gastric acid and duodenal juice have been implicated in Barrett's oesophagus. The aim of this study was to look at duodenal reflux in the oesophagus together with motility characteristics in a group of patients with Barrett's oesophagus and compare them with a mild oesophagitis group and to assess the effect of cisapride on any abnormalities. DESIGN: A prospective study comparing the two groups of patients was carried out. METHODS: Twenty patients with histologically proven Barrett's oesophagus and 20 patients with Savary-Miller grade 2 oesophagitis were studied. Standard oesophageal manometric measurements were carried out and on a separate occasion duodenogastro-oesophageal reflux (DGOR) was measured over a 4-h period using a sodium ion selective electrode. Patients with more than 5% DGOR were given cisapride (10 mg four times daily) and the studies repeated after 7 days of treatment. RESULTS: Barrett's patients showed more DGOR, 12.2% of the study time compared to 5.1% in the mild oesophagitis group, P = 0.012, but manometric findings were not significantly different. Sixteen patients were treated with cisapride. DGOR was reduced in 8 out of 12 Barrett's patients and 2 out of 4 oesophagitis patients, and proximal amplitude and distal oesophageal pressures were significantly elevated (P = 0.05 and P = 0.03, respectively). CONCLUSION: Monitoring of sodium ions in the oesophagus shows that patients with Barrett's oesophagus have significantly more DGOR than patients with uncomplicated oesophagitis and cisapride may be effective in removal of this reflux.

Adult↗

Randomised, prospective, single-blind comparison of laparoscopic versus small-incision cholecystectomy.

BACKGROUND: We report a prospective randomised comparison between laparoscopic and small-incision cholecystectomy in 200 patients which was designed to eliminate bias for or against either technique. METHODS: Patients were randomised in the operating theatre and anaesthetic technique and pain-control methods were standardised. Four experienced surgeons did both types of procedure. Identical wound dressings were applied in both groups so that carers could be kept blind to the type of operation. FINDINGS: There was no significant difference between the groups for age, sex, body mass index, and American Society of Anaesthesiologists grade. Laparoscopic cholecystectomy took significantly longer than small-incision cholecystectomy (median 65 [range 27-140] min vs 40 [18-142] min, p<0.001). The operating time included operative cholangiography which was attempted in all patients. We found no significant difference between the groups for hospital stay (postoperative nights in hospital, median 3-0 [1-17] nights for laparoscopic vs 3-0 [1-14] nights for small-incision, p=0.74), time back to work for employed persons (median 5-0 weeks vs 4.0 weeks; p=0.39), and time to full activity (median 3-0 weeks vs 3.0 weeks; p=0.15). INTERPRETATION: Laparoscopic cholecystectomy takes longer to do than small-incision cholecystectomy and does not have any significant advantages in terms of hospital stay or postoperative recovery.

Analgesia, Patient-Controlled↗

Detection of duodenal fluid in the oesophagus with a sodium ion selective electrode.

The assessment of duodeno-oesophageal reflux is difficult as, until recently, no technique has been readily available for continuous ambulatory monitoring. A sodium ion selective electrode placed in the stomach has been previously shown to detect duodenogastric reflux by using sodium as a marker. This relies on the difference in sodium concentration between gastric (5-60 mmol/L) and duodenal, biliary and pancreatic (150 mmol/L) fluids. In this pilot study to assess the efficacy of the electrode in the distal oesophagus, eight subjects without symptomatic gastro-oesophageal reflux and eight subjects with known duodenogastric reflux were studied. Thirty millilitre volumes of varying sodium solutions (40, 80, 100 and 140 mmol/L) were swallowed to assess the response of the electrode to sodium ions. In both groups, this revealed a constant and reproducible rise in response with increasing concentration (P < 0.0001). The stomachs of subjects with duodenogastric reflux were aspirated via a nasogastric tube to obtain 12 different samples of gastric fluid. This was assayed for sodium and bile acid concentration. The fluid was then reinfused as a 30 mL bolus into the oesophagus through a tube to simulate oesophageal reflux. A rise equivalent to 40-72 mmol/L Na+ was recorded by the electrode in response to samples that contained 58-81 mmol/L Na+ and 0.4-16 mmol/L bile acids, recorded by quantitative analysis, and a response of up to 20 mmol/L Na+ was recorded by the electrode to sodium concentrations < 49 mmol/L and bile acid concentrations of 0.005-0.6 mmol/L. The response was appropriate to the assayed bile acid concentration in all but one sample. The sodium ion selective electrode responds to bile containing fluids introduced into the oesophagus. Further investigation is warranted to determine its ability to measure duodeno-oesophageal reflux continuously.

Bile Acids and Salts↗

Duodenogastric reflux after gastric surgery and in gastric ulcer disease: continuous measurement with a sodium ion selective electrode.

Duodenogastric reflux (DGR) was investigated with a sodium ion selective electrode in 10 normal controls, 10 patients with persistent pain after gastric surgery, and five patients with gastric ulcer. During an average study time of two and a half hours, normal controls had reflux for 12% of the study, whereas patients after gastric surgery had reflux for 91% of the study time (p < 0.0002). Patients with a gastric ulcer had reflux on average for 67% of the study (p < 0.001). The patients who had had gastric surgery had several symptoms, but there was no association between the number or nature of symptoms and the severity of DGR as determined by the sodium electrode. Patients with positive bile provocation tests did not show any significant difference in the duration of reflux compared with those with a negative provocation test (79% and 87%). There was also no relation between the results of the provocation test and the number and nature of symptoms. Continuous monitoring of intragastric sodium ions with a selective electrode is a practical means of assessing DGR. Results suggest that symptoms due to DGR may be related to the sensitivity of the gastric lining as well as the amounts of duodenal contents flowing back into the stomach.

Adult↗

Continuous monitoring of sodium ion concentration in the human stomach--a new technique for the detection of duodenogastric reflux.

Measurement of sodium ion concentration in gastric juice offers a simple means of detecting duodenogastric reflux (DGR). Using aspirated gastric juice, we measured sodium ion concentration, bile acid levels and phospholipase A2 activity and found that sodium ion levels increase along with these other standard markers during DGR. Following this, using a sodium ion selective electrode and a portable data logger, continuous recordings of sodium ion concentration were made in the human stomach. These studies demonstrated the ability of sodium ion monitoring to detect major DGR episodes in the body of the stomach.

Adult↗

Relative contribution of bile and pancreatic juice duodenogastric reflux in gastric ulcer disease and cholelithiasis.

Bile acid concentrations, phospholipase A2 activity and pH in the stomach were measured in the fasting state and for 2 h after a fat-containing test meal in patients with an active gastric ulcer (GU), in patients with gallstones before and after cholecystectomy and in normal subjects. Fasting and peak postprandial bile acid concentrations in the stomach were low in all normal controls. Although high concentrations were found in many patients with GU (P less than 0.01), similar concentrations were found in many patients with radiologically non-functioning gallbladders containing gallstones (NFG) (P less than 0.01) and also after cholecystectomy (AC) (P less than 0.01). Fasting intragastric phospholipase A2 activities were similar, and very high in GU and NFG patients compared with control subjects (P less than 0.01). High values were not found after cholecystectomy. There was no difference in pH profile or in postprandial phospholipase A2 between patient groups. Since patients with cholelithiasis or after cholecystectomy are not known to have an increased incidence of gastric ulceration, the significance of duodenogastric reflux in the aetiology of gastric ulcers must be questioned. If reflux does produce ulcers in GU patients then factors in addition to bile acid are probably involved. However, neither patterns of phospholipase A2 reflux nor pH profiles can explain the absence of gastric ulceration in those patients with gallstones who reflux large quantities of bile acid.

Adult↗

The ability of antacids and cholestyramine to bind bile acids: effect of pH.

Reflux of bile into the stomach may be injurious to the gastric mucosa. The ability of antacids and cholestyramine to bind bile acids is therefore potentially valuable in the treatment of reflux gastritis. The ability of antacids and cholestyramine to remove bile acids from gastric juice, hepatic bile, and solutions of commercially available bile acids was investigated in vitro over a pH range likely to occur in the stomach. The percentage of bile acids removed by antacids decreased with decreasing initial bile acid concentration and usually decreased as the incubation pH was increased from 3.6 to 7.0. Glycine-conjugated bile acids were bound to a greater extent than taurine-conjugated bile acids and dihydroxy to a greater extent than trihydroxy bile acids. Cholestyramine bound 97-100% of all bile acids in solution at pH 3.6 and pH 7.0. The effect of pH on adsorption should therefore be considered when antacids are used to treat gastritis.

Aluminum Compounds↗

An experimental study of the healing of secondary abdominal incisions.

An experimental study of the healing of separate secondary abdominal incisions in rats has been performed. After an initial right subcostal incision, a vertical left-sided abdominal wound was made 1 or 2 weeks later. Wound healing was assessed by measurement of changes in mechanical strength and collagen deposition. The results indicate that an increase in mechanical strength was not effected by initial wounding despite alterations in collagen metabolism.

Abdominal Muscles↗

Does obstructive jaundice adversely affect wound healing?

The effect of obstructive jaundice on wound healing has been investigated in an experimental study of abdominal wounds in rats following ligation and division of the common bile duct. Animals were jaundiced for 2 weeks before a second operation at which the abdominal wounds were made. The wounds in jaundiced and control animals showed no significant differences in mechanical strength during a 21-day period of study but there was a significant delay in the accumulation of collagen in the wounds of jaundiced animals. The findings suggest that the biochemical changes in the wounds of jaundiced animals did not interfere with wound repair and cast doubt on the thesis that jaundice has an adverse effect on wound healing.

Abdomen↗

Neonatal islet cell transplantation in the diabetic rat: effect on the renal complications.

PVG/C rats were made diabetic with streptozotocin and after 1 mth received a single intraperitoneal transplant of isogeneic collagenase digested pancreatic tissue. Renal changes have been studied in transplanted and control diabetic rats using light and electron microscopy and immunological techniques. Following transplantation, renal lesions did not increase in severity and progressive basement membrane thickening was prevented. Ultrastructurally many glomeruli showed a significant reduction in the mesangial matrix and the tubular and mesangial cell changes reverted to normal. Immunofluorescent studies demonstrated a similar reduction in the glomerular deposits of IgG. Possibilities for the treatment of diabetes mellitus in human patients are discussed.

Animals↗

Ascorbic acid requirements in postoperative patients.

The postoperative ascorbic acid requirements of 63 surgical patients were assessed by measurements of buffy layer leukocyte ascorbic acid and the ascorbic acid content of leukocytes. There was a significant reduction in ascorbic acid levels following operation. The postoperative changes were unrelated to the extent of surgical trauma or the volume of blood transfused during operation, but there was a significant correlation between postoperative ascorbic acid measurements and white blood counts. It appears that postoperative leukocytosis and release by the bone marrow of leukocytes with a low ascorbic acid content may partly account for the postoperative changes in buffy layer and leukocyte ascorbic acid measurements. However, surgical operations were followed by an authentic increase in ascorbic acid requirements, and there was a 42 per cent reduction in circulating leukocyte ascorbic acid levels on the third postoperative day. The findings of this study create an argument for the use of ascorbic acid supplements in surgical patients, although it is unlikely that postoperative changes in leukocyte ascorbic acid have pathologic significance in wound repair.

Aged↗

Neonatal islet cell transplantation in the diabetic rat: effect on hepatic enzyme activity and glucose homeostasis.

Intraperitoneal transplantation of collagenase-digested, isogeneic, neonatal rat pancreatic tissue successfully reversed streptozotocin-induced diabetes in 77% of recipients. The low serum immunoreactive insulin, hyperglycaemia, glycosuria and weight loss, characteristic of the diabetic animal, were corrected and the reduced activities of hepatic glucokinase and pyruvate kinase, and the low glycogen concentration of the liver of diabetic rats were restored to normal. Forty-three per cent of the successfully transplanted rats became normoglycaemic within 1 month of transplantation whereas 57% took from 1 to 6 months to achieve normoglycaemia and displayed a mild glucose intolerance when subjected to a glucose load. The rats which had not become normoglycaemic 6 months after transplantation showed some amelioration of the diabetic state, as shown by increased serum immunoreactive insulin and hepatic glycogen concentration and a slow weight gain compared with diabetic controls.

Animals↗