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Biomedical subjects

C R Mackie

Publications and source records attributed to C R Mackie.

At least 19 recordsLinked to original sources

Isotope gastric emptying tests in clinical practice: expectation, outcome, and utility.

Tests of gastric emptying with modern scintigraphic methods are recommended in the clinical management of gastric disorders. An audit of 472 gastric emptying tests carried out over a 10 year period was performed to discover the reasons for requests from consultant clinicians, their anticipation of the results of tests, and the influence of the results upon the subsequent management of their patients. Excluding control (n = 47) and research (n = 50) studies, there were 375 clinical referrals that could be grouped under the headings: non-ulcer dyspepsia (n = 72), suspected diabetic gastroparesis (n = 18), peptic ulcer (n = 15), suspected delayed gastric emptying after surgery (n = 154), dumping and diarrhoea (= 107), and other indications (n = 9). Although the results were abnormal for 55 (48%) of the 'medical' patients, they did not seem to influence clinical management. Delayed gastric emptying after surgery was confirmed in only 20% of patients referred with this clinical diagnosis. Conversely, most (79%) o the patients referred with dumping and diarrhoea exhibited abnormally rapid emptying. Isotope gastric emptying studies may be useful in clinical practice. The results are often at variance with the clinical diagnosis. Clinicians must take into account the nature of the test meal used when results are correlated with clinical features.

Adolescent↗

Gastric adaptive relaxation and symptoms after vagotomy.

Gastric adaptive relaxation is reported to be impaired after vagotomy. This abnormality has been implicated in the pathogenesis of postvagotomy symptoms, but no association has previously been demonstrated between the two. Gastric adaptive relaxation was measured in 15 healthy volunteers and 33 patients more than 1 year after highly selective vagotomy or truncal vagotomy and drainage. Seventeen patients were asymptomatic. The remainder were symptomatic including seven patients with persistent diarrhoea. Fasted subjects were intubated with a Ryle's tube containing a pressure microtransducer within a flaccid (800 ml) plastic bag. Gastric corpus-fundus pressure was recorded during distension of the bag with air (15 ml/s) over 30 s. Pressure indices were derived from the areas under the pressure curves. Median (range) pressure indices were: healthy volunteers 12.7 (7.5-17.1) cmH2O, highly selective vagotomy 14.0 (9.8-15.9) cmH2O (n.s.), truncal vagotomy and drainage 14.5 (8.6-26.8) cmH2O (P = 0.04). All patients with diarrhoea had abnormally high pressure indices (P less than 0.001). Pressure indices in all other patient groups were within the normal range. We conclude that gastric adaptive relaxation remains abnormal in patients with postvagotomy diarrhoea but not in those who are asymptomatic or who have other symptoms.

Adaptation, Physiological↗

Treatment of severe postvagotomy/postgastrectomy symptoms with the somatostatin analogue octreotide.

Fourteen patients with severe and persistent postvagotomy/postgastrectomy symptoms were entered into a trial of treatment with the somatostatin analogue octreotide, 50 micrograms twice daily 30 min before meals being self-administered by subcutaneous injection. Six of the seven patients completing the 3-month trial showed sustained overall improvement of symptoms. The remaining patients were unhelped by treatment or developed unwanted effects. Six of eight patients with dumping syndrome showed sustained improvement of dumping symptoms during treatment. Bile vomiting was relieved in three of four patients with this complaint. Diarrhoea accompanying dumping showed a variable response to treatment, with improvement in three patients and no change or worsening of this symptom in five. Two patients with severe postvagotomy diarrhoea alone showed no improvement. Four patients with unwanted effects and three patients who found no benefit stopped the trial medication early. Four further patients reported mild or transient side-effects. For patients with severe postvagotomy/postgastrectomy symptoms, a trial of octreotide seems justified when significant dumping symptoms are present and other treatment options have been exhausted.

Adult↗

Abnormal gastric adaptive relaxation in patients with gastrooesophageal reflux.

Gastric adaptive relaxation was measured in 15 healthy volunteers (control group) and in 12 patients with symptomatic gastrooesophageal reflux confirmed by 24 hour pH monitoring (reflux group). The control group were: 13 men, two women; median age 30 years, range 22-41; median body weight 70 kg, range 50-79 kg. All were asymptomatic on no medication. The reflux group were: eight men, four women, median age 48 years, range 23-65; median body weight 77 kg, range 60-92 kg. Medication was withheld for 12 hours before the study. Endoscopy showed no abnormality in five patients, oesophagitis in three patients and oesophagitis with hiatus hernia in four patients. Fasted subjects were intubated with a Ryle's tube containing a pressure microtransducer within a flaccid plastic bag (800 ml). Gastric corpus-fundus pressure was recorded during distension of the bag with 460 (20) ml mean (SD) of air over 30 seconds. Pressure indices (median: range) derived from areas under the pressure curves during distension were: control: 12.7 (7.5-17.1) cm H2O; reflux: 9.1 (6.4-13.3) cm H2O, p less than 0.01 (Mann Whitney U test). Similar results were obtained from pressure indices derived from recordings during the immediate postdistension period. No correlation was found between pressure indices and age, sex or body weight. The results indicate that the gastric pressure response to distension is reduced in patients with gastrooesophageal reflux.

Adaptation, Physiological↗

Relationship between gastric emptying of liquid and postvagotomy diarrhoea.

Gastric emptying of liquid was studied in 10 normal volunteers and in 27 patients previously treated with truncal vagotomy and drainage. Thirteen of the twenty-seven patients complained of persistent postvagotomy diarrhoea. For each study 300 ml 15 per cent dextrose, labelled with 99mTc-diethylene triamine penta-acetic acid (DTPA), was ingested at a standard rate by subjects who sat facing a gamma camera. Imaging proceeded for 30 min. Gastric area activity curves were corrected for emptying of the test meal during ingestion, and for movement using a new image alignment technique. Gastric emptying at 15 min was 10 +/- 2.6 per cent (mean +/- s.e.m.) in healthy volunteers, 48 +/- 7.3 per cent in patients without diarrhoea, and 84 +/- 2.3 per cent in those with diarrhoea (P less than 0.001, ANOVA). Gastric emptying from 15 min onwards was slower than normal in both patient groups (P less than 0.001). These results show that initial gastric emptying is rapid following truncal vagotomy and drainage, and this change is greater in patients with postvagotomy diarrhoea. No patient with diarrhoea had normal initial gastric emptying.

Adult↗

Preduodenal mechanisms in initiating gallbladder emptying in man.

The existence of preduodenal phases of gallbladder emptying in normal volunteers was investigated by evaluating the effect of sham feeding a sandwich (chew and spit) (n = 15), the sight and smell of food followed by sham feeding a cooked meal (n = 15), and gastric distension (intragastric balloon tube) (n = 9) on gallbladder emptying and comparing these responses with those after ingestion of a standard meal (n = 14). A control group given no intestinal stimuli were studied to determine the frequency of spontaneous emptying during fasting (n = 18). 99mTc-EHIDA (2,6 diethylphenylcarbamoylmethyliminodiacetic acid) was used as the biliary tracer. The frequency of gallbladder emptying during fasting was 0.0045/min. Thus, in any 20 min period emptying occurred spontaneously in only about 1 in 11 volunteers. Significant emptying (greater than 5 per cent over 20 min) occurred in 8 out of 15 volunteers after sham feeding a sandwich (P less than 0.001 versus control), in 8 out of 15 volunteers after sham feeding a cooked meal (P = 1.0 versus sandwich sham feed, n.s.), in 6 out of 9 volunteers after gastric distension (P less than 0.001 versus control) and in 14 out of 14 volunteers after meal ingestion. The rate of emptying was significantly greater in the gastric distension and meal ingestion groups compared with other groups (P less than 0.05). However, the emptying rate after sham feeding was not significantly different from spontaneous gallbladder emptying (P greater than 0.05, n.s.). There was no significant difference in time to onset of emptying between the four stimulus groups (P greater than 0.05, n.s.). These results suggest that pre-duodenal stimuli can evoke gallbladder emptying in man, although the precise physiological significance of this phenomenon remains to be established.

Adolescent↗

Intragastric bile does not perturb gastric emptying of liquids in humans.

Gastric stasis and duodenogastric reflux have each been implicated in the pathogenesis of various upper gastrointestinal disorders. However, the relationship between intragastric bile and gastric emptying has not been explored. In each of nine healthy volunteers (seven men and two women, ages 22-47 years), gastric emptying of 300 ml 10% dextrose labeled with [99mTc]DTPA was measured twice using gamma camera imaging. During one study, 20 min after ingestion of the test meal, 525 mg of freeze-dried, sterilized human T-tube bile dissolved in 20 ml water was introduced into the stomach via a previously sited fine-bore nasogastric tube. Intragastric bile salt concentrations were calculated to be within the range 1.7-2.9 mM. In control studies, 20 ml of water alone was similarly introduced. Emptying at 20 min was comparable for both groups of studies (38 +/- 3% vs 39 +/- 4%; mean values +/- SEM). For each individual study, emptying from 20 to 60 min was well represented by a single exponential function (r = 0.81-0.99). Half-emptying times for curves fitted over this period were similar in the two groups (bile: T1/2 = 18.8 +/- 2.6 min; control T1/2 = 18.8 +/- 1.9 min). These results indicate that intragastric bile, in concentrations similar to those found in patients with gastric ulcer, has no effect on gastric emptying of dextrose in normal subjects.

Adult↗

Mechanisms governing the biphasic pattern of gastric emptying after truncal vagotomy and pyloroplasty.

The pattern of gastric emptying after truncal vagotomy and drainage is usually biphasic. An early rapid phase is followed by a characteristically abrupt transition to slow emptying. The mechanisms responsible for this pattern were studied in six dogs with truncal vagotomy and pyloroplasty, fitted with a proximal duodenal cannula. Gastric emptying was measured using gamma camera imaging of a radiolabelled 15% dextrose test meal. Sixty one hour studies were done using five designs. (1) With the cannula closed gastric emptying was initially rapid, followed by stasis (emptying at 15 min - 32% (5.3), 60 min - 34% (4.8); mean (SE)). (2) With the cannula open emptying was very rapid (15 min - 76% (4.2) p less than 0.001, 60 min - 88% (2.6) p less than 0.001 ANOVA). (3) Distal duodenal instillation of isotonic saline, at a rate equivalent to gastric emptying with the cannula closed, did not retard this rapid emptying (15 min - 78% (10.6), 60 min - 90% (5.4)). (4) With duodenal instillation of 15% dextrose, gastric emptying remained faster than in studies without diversion (15 min - 50% (7.0) NS, 60 min - 65% (6.8) p less than 0.01), but was slower than during diversion alone (p less than 0.05). (5) Finally, duodenal instillation of 15% dextrose before administration of the test meal produced slower initial emptying without subsequent stasis (15 min - 24% (4.5), 60 min - 47% (10.6)), although the amounts emptied were not significantly different from those with the cannula closed. These results indicate that after truncal vagotomy and pyloroplasty small bowel resistances play a significant role in controlling gastric emptying. Osmoreceptor responses persist after truncal vagotomy, but sympathetic inhibitory responses to small bowel distension are not involved in the regulatory process.

Animals↗

Abnormal pattern of gastric emptying of liquid in chronic duodenal ulcer.

Gastric emptying was measured in 12 patients with chronic duodenal ulceration and compared with the results from 10 healthy volunteers. The test meal of 300 ml 15% dextrose, labelled with 99mTc-DTPA, was ingested in increments over 6 min. Gamma camera imaging proceeded over 30 min, with a 1-min frame time. A direct correction was applied for the fraction emptying into the small bowel during the ingestion period. Gastric emptying at 6 min was significantly greater in the group with duodenal ulcer (14.4 +/- 2.7% vs. 4.2 +/- 0.9%: mean +/- SEM, p less than 0.01). From this time onwards there were no significant differences in the rates of gastric emptying. These results suggest that chronic duodenal ulcer is associated with an abnormal pattern of gastric emptying of liquid, characterised by an initial rapid phase.

Adult↗

Gall bladder emptying in normal subjects--a data base for clinical cholescintigraphy.

Biliary excretion scintigraphy with a cholagogic test meal may be used to assess patients with suspected disorders of gall bladder motility. The interpretation of results is frustrated, however, by the lack of information about the range of normal responses in a form suitable for comparative analysis. We present the results of 41 gall bladder emptying studies on 32 normal healthy subjects (14 men, 18 women) 30 minutes after intravenous injection of 74 MBq 99Tcm-EHIDA. Gall bladder emptying was provoked by the ingestion of 300 ml milk. Gamma camera scintigraphy was used to plot gall bladder activity against time. Gall bladder emptying occurred within 10 minutes in all men and 12/18 women (p = 0.02). Gall bladder ejection fractions were significantly greater in women (p less than 0.05). Duplicate studies in nine subjects showed good reproducibility (r = 0.959). A plot of mean and (m + 2 SD) values of gall bladder activity against time has been derived. The data provide an estimate of normal gall bladder emptying response, which may be used to aid interpretation of clinical studies.

Adult↗

Small bowel resistances and the gastroduodenal brake.

Osmoreceptors in the upper small bowel may delay gastric emptying by inhibiting fundal tone and/or by increasing outflow resistances. In this study we examined the contribution of postpyloric resistances to this braking system. Seven dogs had gastric emptying of 250 ml 15% dextrose, labelled with 99mTc-DTPA, measured by gamma camera imaging (preoperative studies: n = 21). A proximal duodenal cannula was inserted and studies repeated in four modes: with the cannula closed (n = 14); with total diversion of gastric effluent through the cannula (n = 7); with diversion and downstream reinstillation of effluent at a constant rate (n = 14) equivalent to emptying calculated from studies without diversion; and with diversion and total reinstillation of effluent (n = 14). Gastric emptying at 90 minutes was similar in preoperative studies (48 +/- 5% - mean +/- SEM) and in those with the cannula closed (50 +/- 3%). By comparison 'total diversion' produced rapid emptying over 90 minutes (97 +/- 1%; p less than 0.001). Reinstillation of effluent at a constant rate reduced the 90 minute emptying to 59 +/- 6%, and total reinstillation slowed emptying further to 37 +/- 4% (p less than 0.05). Neither reinstillation protocol yielded gastric emptying rates that were significantly different from those in studies without diversion. With total reinstillation, emptying and hence reinstillation rates were more variable, proceeding in a step and plateau fashion. We conclude that canine jejunal osmoreceptor activity is mediated through the stomach, with postpyloric resistances playing little or no role. Gastric emptying curve analysis suggested that increments of rapid small bowel filling provoke exaggerated braking responses.

Animals↗

Surgical pathology at early elective operation for suspected acute gallstone pancreatitis: preliminary report of a prospective clinical trial.

Fifty-five patients presenting with acute abdominal symptoms and found to be hyperamylasaemic underwent early biliary tract investigation, giving 31 patients in whom the presence of gallstones was suspected. In accordance with the protocol of a randomized controlled trial of early elective biliary tract surgery for patients suspected of having acute gallstone pancreatitis, 19 of these patients underwent laparotomy at a mean of 6.9 days after emergency admission. In this group operation showed that four patients had biliary tract stones and pancreatitis; ten patients had calculous cholecystitis (53 per cent) but no stigmata of pancreatitis; four patients had pancreatitis but no stones; one had a negative laparotomy. None of this group was found to have ampullary obstruction due to an impacted stone. Biliary tract investigations carried out during the first week following admission were unhelpful or misleading in 14 out of the whole group of 55 patients, and in all of those patients (11 per cent) who died or required surgical intervention during the same hospital admission. There appears to be a pathological heterogeneity among patients diagnosed as 'gallstone pancreatitis' on clinical and biochemical grounds alone.

Acute Disease↗

Effects of somatostatin and a long-acting somatostatin analogue on the prevention and treatment of experimentally induced acute pancreatitis in the rat.

The effects of somatostatin (SRIF) and its long-acting analogue, SMS 201-995 on the prevention and treatment of acute pancreatitis were studied in rats. Acute pancreatitis was established by ligating the bile duct at the point of entry into the duodenum, thereby allowing reflux of bile into the pancreas. Administration of SRIF (4 micrograms kg-1 body wt IV followed by a 12 h infusion of 4 micrograms kg-1 body wt h-1) or SMS 201-995 (2 micrograms kg-1 body wt SC) at the time of bile duct ligation prevented the increase in the serum concentrations of amylase and lipase observed in control rats 12 h after bile duct ligation. Moreover, SRIF and SMS 201-995 administration prevented development of the histological changes consistent with acute pancreatitis observed in control animals. These results suggest that SRIF or SMS 201-995 may be of value in preventing acute pancreatitis following ERCP or after surgery on the pancreas. In rats with established pancreatitis, SRIF (IV bolus of 4 micrograms kg-1 body wt followed by a 24 h continuous infusion of 4 micrograms kg-1 body wt h-1) or SMS 201-995 (2 micrograms kg-1 body wt SC followed by a similar dose 12 h later): (1) significantly improved survival; (2) produced histological changes in the pancreas consistent with organization and healing; (3) prevented the accumulation of ascitic fluid; (4) reduced the serum levels of amylase and lipase. These results suggest that SRIF and SMS 201-995 may prove valuable in the treatment of established acute pancreatitis in man.

Acute Disease↗

Prophylactic postoperative nasogastric decompression. A prospective study of its requirement and the influence of cimetidine in 200 patients.

To determine the need for prophylactic nasogastric decompression following laparotomy and the influence of cimetidine, 200 consecutive patients who underwent major abdominal procedures were prospectively randomized into one of four limbs: no tube-placebo; no tube-cimetidine; tube-placebo; and tube-cimetidine. Patients were evenly distributed among these groups with respect to age, sex, alcohol and tobacco use, previous operations, and types of operations. There was significantly longer time until passage of flatus, bowel movement, and cessation of intravenous fluids in the tube group (p less than 0.05). Duration of postoperative stay increased from 11.4 to 14.1 days in the intubated patients (p less than 0.05). There was also significantly more pain with and frequency of swallowing, and nose/throat discomfort in the tube group. Nasogastric tubes reduced the incidence of vomiting from 28 in the no-tube group to 10 in the tube group (p less than 0.05), but most had only one or two episodes. Cimetidine did not affect either the incidence of vomiting or the duration of intubation, but was associated with a significant increase in pneumonias (p less than 0.05). Five patients without tubes initially, and seven patients with tubes had to have them inserted or replaced for vomiting or abdominal distention, which occurred equally in the placebo and cimetidine limbs. There were no cases of aspiration pneumonia, gastric dilatation, or wound dehiscence in the trial, and the four anastomotic leaks were divided equally between the tube and no-tube groups. The results indicated that prophylactic decompression was unnecessary in most patients and associated with increased morbidity and delayed return of gastrointestinal function. Cimetidine lowered nasogastric output on the first postoperative day (p less than 0.05), but did not prevent vomiting.

Cimetidine↗

Treatment of acute pancreatitis with fresh frozen plasma.

A consecutive series of 239 patients experiencing 336 separate attacks of acute pancreatitis have been treated with fresh frozen plasma during the first 5 days of the illness. Using established criteria, 96 attacks occurring in 69 patients were judged to be severe at the time of admission. The overall mortality was 3.7 per cent per patient population and 2.7 per cent per total number of separate attacks. Four of 69 patients with severe pancreatitis (5.8 per cent) have died and the mortality rate for the 96 severe attacks was 4.2 per cent. No complications which could be directly attributed to fresh frozen plasma were encountered in the series. The results of this prospective pilot study with naturally occurring human proteinase inhibitors have been encouraging and indicate the need for randomized clinical trials.

Acute Disease↗