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2.  Intravenous midazolam: a study of the degree of oxygen desaturation occurring during upper gastrointestinal endoscopy. 
Intravenous midazolam (mean dose of 6.3 mg) was given to 100 consecutive patients coming to endoscopy. All patients had an ear oximeter attached throughout the procedure to record continuously their levels of oxygen saturation. Eighty-five of the 100 patients had pre-endoscopy respiratory function tests measured, and 82 wore an induction plethysmograph vest to get a continuous qualitative estimate of respiratory rate and excursion throughout the procedure. Following intravenous midazolam a reduction in respiratory excursion was observed in 80% of patients. The initial baseline oxygen saturation of 95.4% fell 3.3% (P less than 0.0005) following intravenous midazolam to 92.1%. During the endoscopic procedure there was a further 3.1% decrease in oxygen saturation to 89.0% (P less than 0.0005) and in 7% the level fell to below 80%. Age, sex, dose of midazolam given and pre-endoscopy respiratory function tests failed to identify those patients at risk of hypoxia during the endoscopy.
PMCID: PMC1386164  PMID: 3606930
3.  Delayed release peppermint oil capsules (Colpermin) for the spastic colon syndrome: a pharmacokinetic study. 
Excretion of menthol (as glucuronide) from orally ingested peppermint oil contained in Colpermin was compared with oil contained in two soft gelatine capsules. Total 24 h urinary excretion of menthol was similar in the two formulations in healthy volunteers, but peak menthol excretion levels were lower and excretion delayed with Colpermin. Menthol excretion was reduced in ileostomy patients who took Colpermin and moderate amounts of unmetabolised menthol were recovered from the ileostomy effluent. This is consistent with Colpermin being a delayed-release form of peppermint oil.
PMCID: PMC1463599  PMID: 6487507
5.  Biopsy specimen appearances of ischaemic gastritis in splanchnic arterial insufficiency. 
Journal of Clinical Pathology  1998;51(3):255-256.
A 74 year old man presented with a one month history of epigastric discomfort, anorexia, weight loss, and postprandial vomiting. The diagnosis of ischaemia was made on endoscopic biopsies from the stomach and duodenum. He was too ill for major vascular surgery and died eight days after admission. Postmortem examination confirmed the diagnosis of splanchnic arterial insufficiency caused by atheroma and thrombosis. Ischaemic gastritis is rare but could easily be missed in unrepresentative biopsy specimens. Prompt diagnosis with revascularisation surgery is the only hope for long term survival.
PMCID: PMC500654  PMID: 9659275
7.  First clinical results with a real time, electronic imager as an aid to colonoscopy. 
Gut  1995;36(6):913-917.
The early clinical results are described of a real time, electromagnetic imaging system as an aid to colonoscopy. After gaining experience with the use of the system, one experienced endoscopist was randomised to perform consecutive colonoscopies either with (n = 29) or without (n = 26) the imager view. All procedures were recorded on computer disk and replayed for retrospective analysis. Total colonoscopy was achieved in all patients except one (imager view not available). Comparing intubation time and duration of loop formation per patient, there was no significant difference between the two study groups. The number of attempts taken to straighten the colonoscope pre patient, however, was less when the endoscopist was able to see the imager view, p = 0.03. Hand pressure was also more effective when the endoscopist and endoscopy assistant could see the imager display, p = 0.02. Preliminary experience suggests that real time, electronic imaging of colonoscopy is safe, effective, and will improve the accuracy of the procedure.
PMCID: PMC1382632  PMID: 7615283
8.  Guidelines on appropriate indications for upper gastrointestinal endoscopy. Working Party of the Joint Committee of the Royal College of Physicians of London, Royal College of Surgeons of England, Royal College of Anaesthetists, Association of Surgeons, the British Society of Gastroenterology, and the Thoracic Society of Great Britain. 
BMJ : British Medical Journal  1995;310(6983):853-856.
Upper gastrointestinal endoscopy is a valuable diagnostic tool, but for an endoscopy service to be effective it is essential that it is not overloaded with inappropriately referred patients. A joint working party in Britain has considered the available literature on indications for endoscopy, assessed standard practice through a questionnaire, and audited randomly selected cases using an independent panel of experts and an American database system. They used these data to produce guidelines on the appropriate and inappropriate indications for referral for endoscopy, although they emphasise that under certain circumstances there may be reasons to deviate from the advice given. The need for endoscopy is most difficult to judge in patients with dyspepsia, and this aspect is discussed in detail. Early endoscopy will often prove more cost effective than delaying until the indications are clearer.
PMCID: PMC2549224  PMID: 7711627
9.  Small bolus injections of intravenous midazolam for upper gastrointestinal endoscopy: a study of 788 consecutive cases. 
1 A recent audit of upper gastrointestinal endoscopy carried out by the Royal College of Surgeons of England has shown that the majority of endoscopists use a bolus injection rather than a slow intravenous titration of benzodiazepine for intravenous sedation. In this study we have confirmed the theoretical premise that a reduced dose of midazolam is required when given as a bolus. A mean dose of 4.65 mg midazolam intravenously has been found to be effective and safe in sedating patients under 70 years (n = 552). The dose of midazolam needed is reduced in older patients: patients over 70 years (n = 236) needed a mean dose of 1.89 mg. 2 Topical pharyngeal anaesthesia was not required with these doses of midazolam, and it was our impression that the examination was equally well tolerated with a similar degree of anterograde amnesia as in the previous study. 3 Our data, together with the results of the audit, would suggest many endoscopists are employing unnecessarily large and at times potentially dangerous doses of intravenous sedation in elderly patients and that the vast majority of upper gastrointestinal endoscopies can be performed successfully, without topical pharyngeal anaesthesia, using a bolus injection techniquewith a reduced dosage of sedative agent.
PMCID: PMC1364663  PMID: 12959275
10.  Helicobacter pylori infection and duodenal ulcer. 
BMJ : British Medical Journal  1991;303(6796):248.
PMCID: PMC1670499  PMID: 1884072
11.  Recommendations for standards of sedation and patient monitoring during gastrointestinal endoscopy. 
Gut  1991;32(7):823-827.
(1) Safety and monitoring should be part of a quality assurance programme for endoscopy units. (2) Resuscitation equipment and drugs must be available in the endoscopy and recovery areas. (3) Staff of all grades and disciplines should be familiar with resuscitation methods and undergo periodic retraining. (4) Equipment and drugs necessary for the maintenance of airway, breathing, and circulation should be present in the endoscopy unit and recovery area (if outside the unit) and checked regularly. (5) A qualified nurse, trained in endoscopic techniques and adequately trained in resuscitation techniques, should monitor the patient's condition during procedures. (6) Before endoscopy, adverse risk factors should be identified. This may be aided by the use of a check list. (7) The dosage of all drugs should be kept to the minimum necessary. There is evidence that benzodiazepine/opioid mixtures are hazardous. (8) Specific antagonists for benzodiazepines and opioids exist and should be available in the event of emergency. (9) A cannula should be placed in a vein during endoscopy on 'at risk' patients. (10) Oxygen enriched air should be given to 'at risk' patients undergoing endoscopic procedures. (11) The endoscopist should ensure the well being and clinical observation of the patient undergoing endoscopy in conjunction with another individual. This individual should be a qualified nurse trained in endoscopic techniques or another medically qualified practitioner. (12) Monitoring techniques such as pulse oximetry are recommended. (13) Clinical monitoring of the patient must be continued into the recovery area. (14) Records of management and outcome should be collected and will provide data for appropriate audit.
PMCID: PMC1379003  PMID: 1855692
12.  13C-urea breath test for Helicobacter pylori infection. 
Gut  1991;32(5):551-552.
PMCID: PMC1378939  PMID: 2040481
13.  Sedation for upper gastrointestinal endoscopy: results of a nationwide survey. 
Gut  1991;32(1):12-15.
A postal questionnaire inquiring about routine sedation and premedication practice for upper gastrointestinal endoscopy was sent to 1048 doctors. Of 665 appropriate returns, 81% were from consultant physicians and surgeons. Most endoscopists (90%) reported using an intravenous benzodiazepine for at least three quarters of endoscopies and 54% of physicians and 69% of surgeons always did so. Midazolam was the intravenous sedative used by a third of all respondents and 13% also used an additional intravenous agent, usually pethidine. Over the previous two years a total of 119 respiratory arrests, 37 cardiac arrests, and 52 deaths were identified. Adverse outcomes were reported more frequently by consultant physicians, by those who 'titrated' the intravenous sedative, and by those who used an additional intravenous agent, but were reported equally frequently by endoscopists using midazolam and endoscopists using diazepam. There is an urgent need for a prospective study to identify the circumstances and risk factors associated with adverse outcomes related to endoscopy.
PMCID: PMC1379205  PMID: 1991631
14.  A comparison of diazepam and midazolam as endoscopy premedication assessing changes in ventilation and oxygen saturation. 
1. One hundred and two consecutive patients undergoing upper gastrointestinal endoscopy were randomised to be sedated with either intravenous diazepam (Diazemuls-Kabi Vitrum) or intravenous midazolam (Hypnovel-Roche). It was assumed that midazolam was likely to be approximately twice as potent as diazepam on the basis of previous work. 2. All patients had an ear oximeter attached throughout the procedure to record continuously their level of oxygen saturation. 3. All 102 patients had pre-endoscopy respiratory function tests measured and 100 wore an induction plethysmograph vest to allow continuous estimation of respiratory rate and excursion. The plethysmograph was calibrated using a pneumotachygraph, so baseline, post-injection and post-endoscopy minute volumes could be estimated. 4. The age, sex ratio and pre-endoscopy respiratory function tests of the 51 patients given intravenous diazepam in a mean dose (s.d.) of 11.5 (5.8) mg over a mean of 3.4 (0.9) min) were similar to that of the 51 patients sedated with intravenous midazolam (mean dose 6.0 (2.8) mg over 3.3 (0.9) min. 5. Both drugs significantly reduced minute volume (P less than 0.001) and oxygen saturation (P less than 0.001). Midazolam appeared to produce slightly greater hypoxaemia with 57% having falls in oxygen saturation of greater than 2.5% compared with only 35% given an equivalent dose of diazepam. 6. Ventilation was still less than baseline when re-checked some minutes after removal of the gastroscope. The speed of recovery appeared faster after diazepam sedation which is in contrast to its longer pharmacological half-life.(ABSTRACT TRUNCATED AT 250 WORDS)
PMCID: PMC1386637  PMID: 3061425
16.  Stones in the common bile duct: experience with medical dissolution therapy. 
Postgraduate Medical Journal  1985;61(714):313-316.
Thirty-one patients with radiolucent common bile duct stones received medical treatment. Nineteen had Rowachol, a terpene preparation, eight (42%) achieving complete stone disappearance within 3 to 48 months. Fifteen (including 3 of the above) took Rowachol with bile acid (chenodeoxycholic in 11, ursodeoxycholic in 4) for 3 to 60 months: 11 (73%) achieved complete dissolution within 18 months. Persistent symptoms and complications settled on conservative management: 8 (25%) patients required admission (2 biliary colic, 1 obstructive jaundice, 4 cholangitis, 1 pancreatitis). One patient died of a myocardial infarction during recovery from pancreatitis; the other continued treatment, 2 achieving complete dissolution/disappearance. Oral dissolution therapy with Rowachol and bile acids should be considered when endoscopic sphincterotomy or surgery is not feasible, but careful attention to potential complications is required while stones persist.
PMCID: PMC2418220  PMID: 4022860
17.  Intravenous midazolam for upper gastrointestinal endoscopy: a study of 800 consecutive cases relating dose to age and sex of patient. 
In many endoscopy units midazolam is replacing diazepam as the intravenous sedative of first choice. Midazolam is approximately twice as potent as diazepam. Although generally considered a safe drug, there have been a number of recent reports, particularly in the elderly, of the drug causing hypotension, respiratory depression and even death. There have been at least ten studies comparing diazepam with midazolam for upper gastrointestinal endoscopy but many have involved relatively small numbers and none have adequately addressed the question of dosage in the elderly. We have carefully recorded the dose of intravenous midazolam used to produce adequate sedation prior to upper gastrointestinal endoscopy in 800 consecutive patients. The dose of midazolam decreased markedly with age in both male and female patients. There was a highly significant correlation in both sexes between age and the dose of midazolam (rho -0.787, P less than 0.001 for males and rho -0.768, P less than 0.001 for females). There was only a small difference in dose in men and women, an average of 1 mg; and no difference in dose over the age of 70 years. In patients over 70 years of age the dose of midazolam necessary for endoscopy is often so small that overdosage is all too easy.
PMCID: PMC1386076  PMID: 3828200
18.  The effects of 3,5,5-trimethylcyclohexanol on hepatic cholesterol synthesis, bile flow and biliary lipid secretion in the rat. 
British Journal of Pharmacology  1984;81(1):183-187.
The chemical trimethylcyclohexanol (TMC) is closely related to menthol, the major component of a terpene preparation with known choleretic and cholelitholytic activity. Its effects on hepatic cholesterol synthesis and bile secretion were examined in the rat. In both acute and long-term dosing experiments TMC significantly inhibited hepatic S-3-hydroxy-3-methylglutaryl coenzyme A (HMGCoA) reductase. TMC was a potent choleretic, with detectable effects on bile flow at low doses, which also reduced coupling of cholesterol secretion to bile salt secretion. Single large doses tended to lower biliary cholesterol output and caused significant reduction in cholesterol saturation index after biliary diversion for 1 h. TMC and its widely prescribed ester cyclandelate, which is rapidly degraded to TMC after ingestion, should be investigated further as potential cholelitholytic treatments in man.
PMCID: PMC1986967  PMID: 6704580
19.  Pilot study of combination treatment for gall stones with medium dose chenodeoxycholic acid and a terpene preparation. 
Thirty patients with radiolucent stones in a radiologically functioning gall bladder were treated for up to two years with a combination of Rowachol (one capsule twice daily), a mixture of cyclic monoterpenes, and chenodeoxycholic acid (7.0-10.5 mg/kg/day). The patients were not selected for body weight or size of stones. All complete dissolutions diagnosed by oral cholecystography were confirmed or refuted by ultrasound examination. Control of symptoms was excellent, only one patient withdrawing from the study because of persistent biliary pain. No evidence of hepatotoxicity was detected biochemically, and diarrhoea due to chenodeoxycholic acid was minimal at this dose. Stones disappeared completely in 11 patients (37%) within one year and in 15 (50%) within two years. These results compared favourably with those obtained with similar doses of chenodeoxycholic acid alone, in particular those of the National Co-operative Gallstone Study (complete dissolution in 13.5% of patients at two years). Treatment with a combination of medium dose chenodeoxycholic acid with Rowachol for radiolucent gall stones is economical, effective, and likely to minimise persistent symptoms and adverse effects of treatment.
PMCID: PMC1442019  PMID: 6430390
21.  Gall-stone dissolution and recurrence: are we being misled? 
Oral cholecystography repeated at six-months intervals is the standard method for determining reduction in size of gall stones (partial success) and complete dissolution of stones (complete success). In a comparative study of oral cholecystography and cholecystosonography six out of 14 patients with gall stones achieving complete success by oral cholecystographic criteria had stones still detectable by ultrasonography. Repeat oral cholecystography in a further 11 patients receiving post-dissolution maintenance treatment detected stones in two, whereas ultrasonography detected stones in seven. In future complete dissolution of gall stones should be reported only if both oral cholecystography and ultrasonographic studies give negative results and the progress of patients receiving post-dissolution maintenance treatment is monitored by ultrasonography rather than serial oral cholecystography.
PMCID: PMC1498166  PMID: 6803946
22.  Outcome of endoscopy and barium radiography for acute upper gastrointestinal bleeding: controlled trial in 1037 patients. 
A study was conducted to find whether the higher diagnostic yield of endoscopy compared with barium radiography improves management or survival in patients with acute upper gastrointestinal bleeding. A total of 1037 patients were entered into a randomised study comparing the outcomes after each investigation. The diagnostic yield in patients who underwent endoscopy was 73% (382 of 526 cases) and in those examined by radiography 55% (280 of 511 cases). A fifth of the patients in the radiology group and a tenth of those in the endoscopy group subsequently underwent the alternative investigation; in most cases, however, no additional diagnostic information was obtained. Operation rates were similar in two groups, though patients in the endoscopy group were generally operated on sooner. Mortality rates were also similar in the two groups, though postoperative mortality was higher in the endoscopy group. Endoscopy may be a more accurate means of diagnosis than radiography, but it offers no short-term benefits in management.
PMCID: PMC1496165  PMID: 6800536
24.  Cimetidine and ranitidine: comparison of effects on hepatic drug metabolism. 
British Medical Journal  1980;281(6243):775-777.
Paired studies of hepatic microsomal function were conducted in eight subjects during treatment with two histamine H2 antagonists, cimetidine and ranitidine. Cimetidine but not ranitidine inhibited the metabolism of antipyrine (phenazone) and demethylation of aminopyrine (aminophenazone) as measured by breath 14CO2 production after intravenous injection of 14C-aminopyrine. These results suggest that the metabolic inhibitory actions on the liver may be separated from H2 antagonist effects, and that ranitidine has an advantage over cimetidine by not inhibiting microsomal drug oxidative function.
PMCID: PMC1714006  PMID: 6107157
25.  Iotroxamide studies in man--plasma binding, renal and biliary excretion studies in jaundiced and anicteric patients. 
1.A decrease in the plasma binding of iotroxamide was found in jaundiced people. 2. The decrease in binding was associated with an enhancement in renal excretion. 3. Iotroxamide consistently gave higher biliary iodine concentrations than ioglycamide.
PMCID: PMC1429469  PMID: 698028

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