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Biomedical subjects

K R Palmer

Publications and source records attributed to K R Palmer.

At least 19 recordsLinked to original sources
PubMed1997

Pharmacokinetics of valsartan in patients with liver disease.

OBJECTIVES: Valsartan (CGP 48933), an orally active angiotensin II antagonist, is eliminated mainly by hepatic clearance. To characterize the compound(s) excreted in the bile, biliary excretion of valsartan was investigated by collection of bile after an intravenous dose of valsartan. In addition, to determine the exposure to valsartan when liver function is impaired, a pharmacokinetic study (open, single dose) was performed in patients with mild and moderate impairment of liver function. PATIENTS: Biliary excretion of valsartan (after intravenous administration of 20 mg valsartan) was assessed in a patient who underwent a hepaticojejunostomy with subsequent bile drainage. Exposure to valsartan in patients with mild (n = 6) or moderate (n = 6) impaired liver function (Child's-Pugh classification) and matching (sex, age, and weight) healthy volunteers (n = 12) was studied after oral administration of a single dose of 160 mg valsartan. RESULTS: After intravenous administration, valsartan was eliminated mainly as unchanged drug in the bile. Mean exposure (measured as area under the plasma valsartan concentration-time curve) to valsartan was increased about twofold in both the mild and the moderate groups compared with matched (age, sex, and weight) healthy volunteers. CONCLUSION: These data are consistent with the pharmacokinetics of valsartan in that biliary excretion is the main route of elimination.

Adult↗
PubMed1997

Quality of life in patients stented for malignant biliary obstructions.

BACKGROUND/AIMS: Endoscopic stent placement is the standard treatment for patients with extrahepatic malignant biliary strictures (EMBS) who are too frail to undergo surgical resection. Stenting relieves jaundice and pruritus but the effects upon other systemic symptoms and quality of life (QOL) are not known. METHODS: Forty-seven patients (age: 46-89 years) with jaundice due to EMBS completed the European Organisation for Research and Treatment of Cancer QOL questionnaire, EORTC QLQ-C30, and two further questions assessing jaundice and pruritus, at the time of diagnosis and 1 month after endoscopic stenting. Thirty-eight patients successfully completed the study; nine patients succumbed to their illness within a month. RESULTS: No significant difference was found in the baseline QOL measurements and liver function tests between those patients who completed the study and those who were either too weak to answer the questionnaire or died within the first month of stenting. For patients who successfully completed follow-up, liver function tests (apart from serum albumin) improved after stenting. They also reported significant improvement in emotional, cognitive and global health scores (P < 0.01). In addition to the expected improvement in pruritus and jaundice (P < 0.01), anorexia, diarrhoea and sleep pattern were also reported to be improved (P < 0.01). CONCLUSION: Endoscopic stent insertion considerably improves a range of symptoms and enhances quality of life.

Aged↗
PubMed1997

Topical glyceryl trinitrate relaxes the sphincter of Oddi.

BACKGROUND/AIM: Nitric oxide (NO) may be involved in non-adrenergic non-cholinergic (NANC) inhibitory innervation of the sphincter of Oddi (SO). The effects of topical application of glyceryl trinitrate (GTN), a NO donor, upon SO motility were examined. METHODS: Nineteen patients undergoing routine SO manometry for investigation of abdominal pain were studied. After routine recording of SO motility, they were randomised into three groups to receive 10 ml of normal saline, 5 mg GTN (0.5 mg/ml) or 10 mg (1 mg/ml) GTN. Drug solutions were infused topically onto papilla via the manometry catheter and recordings were continued for a further 5 minutes. RESULTS: There was no significant change in SO motor variables following application of normal saline. GTN reduced SO tonic and phasic contractions. In four patients, there was complete abolition of all phasic contraction. CONCLUSIONS: Local application of GTN inhibits SO motility. This may have application for diagnostic and therapeutic biliary endoscopy.

Administration, Topical↗
PubMed1997

Influence of cholecystectomy on sphincter of Oddi motility.

BACKGROUND: Gall bladder and sphincter of Oddi (SO) function are coordinated by hormonal and neuronal mechanisms. Nerve fibres pass between the gall bladder and the SO via the cystic duct. It is therefore possible that cholecystectomy may alter SO motility. AIM: To investigate the effect of cholecystectomy on SO function. METHODS: SO manometry was performed in five women (median age 52 years), a few days before and six months after laparoscopic cholecystectomy which was undertaken for uncomplicated cholelithiasis. Basal and post-cholecystokinin (CCK) SO motility were measured. RESULTS: All patients were symptom free after laparoscopic cholecystectomy. Prior to surgery common bile duct pressure, and tonic and phasic SO motility were normal and phasic contractions were inhibited by intravenous CCK (1 Ivy Dog Unit/kg). Six months later, common bile duct pressure and baseline tonic and phasic activity were unchanged but CCK failed to suppress phasic activity. CONCLUSION: Cholecystectomy, at least in the short term, suppresses the normal inhibitory effect of pharmacological doses of CCK on the SO. The mechanism of this effect is unknown but it could be due to SO denervation.

Adult↗
PubMed1997

Reduced long-term survival following major peptic ulcer haemorrhage.

BACKGROUND: The late outcome of patients who present with major peptic ulcer haemorrhage is unclear. An examination was made of the hypothesis that prognosis may be poor because many such patients have severe co-morbid diseases. METHODS: Some 121 patients treated endoscopically for severe peptic ulcer haemorrhage were followed for a median of 36 (range 30-76) months and outcome was compared with that of age- and sex-matched controls. RESULTS: Thirty patients (25 per cent) died during the follow-up period and Kaplan-Meier plots showed reduced survival in patients with ulcers (P < 0.01). Death was restricted largely to patients who had co-morbid diseases. Eight of the remaining 91 patients had further peptic ulcer bleeding; two of these were taking maintenance acid-reducing therapy and only one had significant dyspepsia before rebleeding. Eighty-three per cent of surviving patients had little or no dyspepsia. CONCLUSIONS: The late prognosis of patients who present with major ulcer haemorrhage is poor, but most deaths are a consequence of co-morbid disease and not recurrent ulcer bleeding. Most patients have little dyspepsia and those who rebleed are largely free from dyspepsia.

Adult↗
PubMed1997

Experimental studies of injection therapy for ulcer haemorrhage in rabbits.

BACKGROUND: Endoscopic injection therapy is a well established method of controlling peptic ulcer haemorrhage but the optimum injection solution and the mechanism involved in inducing haemostasis are unknown. METHODS: The efficacy and effects on tissue of various therapeutic agents used in the control of gastric mucosal haemorrhage were studied in ten rabbits. Thirty-eight bleeding mucosal ulcers (blood loss above 1.5 ml/min) created at gastrotomy were studied. Adrenaline (1:100,000), thrombin, fibrin (thrombin plus fibrinogen), 5 per cent ethanolamine and 50 per cent dextrose were injected; a fibrin suspension was also sprayed around bleeding ulcers. RESULTS: Sclerosants were found to be least effective in the control of bleeding and were associated with significant tissue necrosis. Although all the other solutions significantly decreased blood loss within 30 min of injection (median blood loss 0.25 ml/min), only an injected mixture of adrenaline plus thrombin and sprayed fibrin achieved complete haemostasis within 2 min of treatment and with no recurrence of bleeding. Neither agent caused significant tissue damage. Histological examination showed that no solution caused arterial thrombosis when injected next to a major ear artery. CONCLUSION: Sclerosants caused extensive tissue necrosis and were least effective in the control of ulcer haemorrhage. A combination of dilute adrenaline and human thrombin may represent optimal haemostatic therapy for peptic ulcer haemorrhage.

Animals↗
PubMed1996

Role of endoscopic injection therapy in the treatment of bleeding peptic ulcer.

Of patients with peptic ulceration who are actively bleeding at endoscopy, 80 per cent will continue to bleed or rebleed in hospital; 50 per cent of those who have a non-bleeding visible vessel will also rebleed. Endoscopic injection treatment stops active bleeding and prevents further haemorrhage in most of these patients. The mechanism of action may include tamponade, vasoconstriction, sclerosis, tissue dehydration and thrombogenesis; substances injected include adrenaline, sclerosants, alcohol, thrombin, or a combination of agents. Although trials often define the need for surgery as an injection treatment failure, an alternative view is that endoscopic control may facilitate safe, early, elective surgery. A successful outcome may require a combination of endoscopic and operative approaches.

Decision Making↗
PubMed1996

Endoscopic injection for bleeding peptic ulcer: a comparison of adrenaline alone with adrenaline plus human thrombin.

BACKGROUND & AIMS: Endoscopic injection therapy improves outcome in bleeding peptic ulcer, but the optimum regimen is unknown. The aim of this study was to compare the efficacy of endoscopic therapy with dilute adrenaline alone vs. adrenaline plus human thrombin in the treatment of patients with major peptic ulcer hemorrhage. METHODS: One hundred forty patients with significant peptic ulcer hemorrhage and active arterial bleeding or a nonbleeding visible vessel were randomized to endoscopic injection with 1:100,000 adrenaline (70 patients; group 1) or to adrenaline plus 600-1000 IU of human thrombin (70 patients; group 2). The two groups were well matched for age, shock, hemoglobin concentration, comorbid disease, endoscopic findings, and consumption of nonsteroidal anti-inflammatory drugs. RESULTS: Fourteen patients from group 1 (20%) and 3 patients from group 2 (4.5%) rebled (P < 0.005). Seven patients from group 1 (10%) but no patients from group 2 died within 30 days of admission (P < 0.013). Patients from group 1 were administered a total of 297 units of blood compared with 219 units in group 2 (P < 0.041). CONCLUSIONS: Endoscopic injection using adrenaline plus human thrombin is superior to injection with dilute adrenaline alone and may represent the best treatment for bleeding peptic ulcers.

Adult↗
PubMed1996

The outcome of urgent surgery for major peptic ulcer haemorrhage following failed endoscopic therapy.

OBJECTIVE: To review the outcome of patients who underwent emergency surgery for major peptic ulcer haemorrhage after failed endoscopic therapy. To address whether 'conservative' or 'aggressive' surgery is best. DESIGN: A retrospective analysis of emergency surgery for ulcer bleeding which could not be controlled by endoscopic therapy. SETTING: The four admitting units in the Lothian region of Scotland. PARTICIPANTS: Sixty-seven patients who failed endoscopic therapy for bleeding peptic ulcer and underwent emergency surgery between December 1990 and December 1995. Simple underrunning or excision of ulcer alone was done in 31 patients whilst 36 had more radical surgery. MAIN OUTCOME MEASURES: Rebleeding and 30-day mortality rates. RESULTS: Rebleeding was significantly higher in patients treated by underrunning (7 versus 1, P < 0.013). There were fewer deaths in the radically treated group (5 versus 7, not significant). CONCLUSION: Patients undergoing surgical operation for severe peptic ulcer haemorrhage after failed endoscopic therapy may be best served by a relatively aggressive approach.

Aged↗
PubMed1996

Incidence of persistent symptoms after laparoscopic cholecystectomy: a prospective study.

BACKGROUND AND AIMS: Laparoscopic cholecystectomy is the standard treatment for symptomatic gall stone disease. This study aimed to assess the effect of the operation on patients' symptoms. METHODS: One hundred consecutive patients undergoing laparoscopic cholecystectomy between June 1994 and June 1995 were evaluated using standard questionnaires examining demographic details, indication for laparoscopic cholecystectomy, characteristics of pain, and other associated dyspeptic and colonic symptoms. A history of psychiatric disturbances and of hysterectomy were also recorded. The same questionnaires were administered again six months after the operation. Operation notes and histological reports were reviewed. RESULTS: Three patients were converted to open surgery and were excluded from analysis. The median age of the remaining 97 patients was 50.9 (19-85) years; 19 were men. There was one complication each of bleeding and biliary leak. Indications for laparoscopic cholecystectomy were biliary type pain (66 patients) and complicated gall stone disease (acute cholecystitis 21, cholestatic jaundice six, and pancreatitis four). Thirteen patients (13%) had persistent pain and two (3%) developed diarrhoea at follow up. Only one patient with persistent pain after laparoscopic cholecystectomy originated from the complicated gall stone disease group. Logistic discriminant analysis showed that bloating (p < 0.001), constipation (p < 0.05), and previous and current use of psychotrophic drugs (p < 0.001) were significantly more common among those with a poor outcome after laparoscopic cholecystectomy. Heartburn was unaffected. Of patients with persistent symptoms after cholecystectomy 77% had no or mild histological changes of cholecystitis as compared with 30% in the pain free group. CONCLUSIONS: The incidence of persistent pain after laparoscopic cholecystectomy was 13%. Abdominal bloating and psychiatric medications were predictive for persistence of pain after laparoscopic cholecystectomy.

Adult↗
PubMed1996

Failure of Nd-YAG photocoagulation therapy as treatment for Barrett's oesophagus--a pilot study.

INTRODUCTION: Acid suppression therapy and surgical antireflux procedures have not consistently led to regression of Barrett's epithelium. We reasoned that laser photocoagulation in combination with powerful acid suppression might destroy the metaplastic columnar epithelium and allow the area to be replaced by normal squamous mucosa. PATIENTS AND METHODS: Eight patients with endoscopic and histologically proven Barrett's oesophagus were recruited into the study. Four patients were randomized to receive omeprazole 40 mg daily and four patients received the same medical therapy plus repeated laser photocoagulation administered at 4-6 weekly intervals. Endoscopies were performed on entry and at 6 months. The extent of Barrett's epithelium was assessed and mapped on to a grid system and histological changes were assessed in blinded manner by a single histopathologist. One new quadrant of Barrett's segment was irradiated per treatment. RESULTS: Laser therapy was well tolerated and no complications occurred. After 6 months, the extent of Barrett's epithelium was unchanged in both groups. There was no appearance of squamous islands either endoscopically or microscopically in areas treated with laser. CONCLUSION: Nd-YAG laser is ineffective in ablating Barrett's epithelium.

Adult↗
PubMed1996

Extracorporeal shock wave lithotripsy for bile duct stones using a piezoelectric lithotriptor: the Scottish lithotriptor centre experience.

There is less published data on the use of piezoelectric lithotripsy in the management of bile duct stones than on electrohydraulic or electromagnetic lithotripsy. We report our experience in treating 20 patients with large bile duct stones (median size 20 mm; range 15-30 mm) which could not be extracted endoscopically. Stone fragmentation was achieved in 75% of the patients and the bile duct was cleared in 65% of the patients. There were no procedure related complications and no 30-day mortality. None of the patients required any sedation or analgesia and all the sessions were well-tolerated. We conclude that piezoelectric lithotripsy is a safe and moderately effective option for difficult bile duct stones. It has the advantage that it is well-tolerated without the need for sedation or analgesia.

Aged↗
PubMed1995

Age-related mortality in patients treated endoscopically for bleeding peptic ulcer.

Before the widespread use of endoscopic therapy, mortality from peptic ulcer hemorrhage was highest in elderly patients, and many deaths in this group were a consequence of postoperative complications. Endoscopic intervention greatly reduces the need for an emergency surgical operation, and consequently increasing age may no longer be a risk factor for death from bleeding ulcer. To examine this hypothesis, the outcome of 326 patients undergoing endoscopic therapy for bleeding peptic ulcer was related to age. One hundred two patients were less than 60 years of age (group I), 116 were 61 to 74 years of age (group II), and 108 were older than 75 years (group III). More group III patients were women (p < .0001) and were receiving nonsteroidal anti-inflammatory drugs (p < .0001). Associated concomitant diseases were significantly more common in group II and group III patients (p < .001). Forty-nine (45%) group III patients bled from gastric ulcers. More of group II patients were receiving anticoagulant drugs (p < .005). A previous history of peptic ulcer was most common in group I (p < .005), and duodenal ulcer was usually the cause of bleeding in this group. The three groups were well matched in terms of endoscopic stigmata (active bleeding and nonbleeding vessel), admission hemoglobin concentration, the presence of shock, and total transfusion requirements. Endoscopic therapy (injection or heater probe) was possible in 95% of all patients. The need for surgical intervention tended to be lowest in group I (11%, 19%, and 18%), whereas hospital mortality (3%, 6%, and 5%) was very similar. In this large group of unselected patients with major peptic ulcer bleeding, age did not significantly influence response to endoscopic therapy or hospital mortality.

Adolescent↗
PubMed1995

Successful Helicobacter pylori eradication incorporating a one-week antibiotic regimen.

BACKGROUND: The optimum regimen for the eradication of Helicobacter pylori remains unclear. The aim of this study was to determine the efficacy and tolerability of omeprazole 40 mg daily given for 2 weeks, plus amoxycillin 500 mg t.d.s. and metronidazole 400 mg t.d.s. given for the first 7 days, in the treatment of H. pylori associated peptic ulcer disease. RESULTS: One hundred and thirty-two consecutive patients with peptic ulcer disease were entered into the study (89 male, 41 female; median age 47 years; inter-quartile range: 36-58 years). H. pylori was eradicated successfully in 109 of 130 patients (intention-to-treat: 83%; 95% confidence limits: 76-89%); per protocol: 85% (95% CI: 78-91%)). Ninety per cent of patients completed the full course of therapy. Only four patients (3%) stopped treatment as a result of side effects although these occurred in 41% of patients. One patient developed pseudomembranous colitis requiring hospital admission. CONCLUSION: Omeprazole combined with one week of treatment of amoxycillin and metronidazole is an effective and well tolerated Helicobacter eradication regimen. Occasional severe side effects remain a risk, even when the duration of antibiotic exposure is reduced.

Adult↗
PubMed1995

Eradication of Helicobacter pylori and prevention of recurrence of duodenal ulcer: a randomized, double-blind, multi-centre trial of omeprazole with or without clarithromycin.

BACKGROUND: Antimicrobial treatment for Helicobacter pylori eradication is currently recommended for all patients with duodenal ulcer disease, but consensus on the best treatment is lacking. METHODS: Patients with active duodenal ulcer and H. pylori were enrolled in a double-blind, randomized, placebo-controlled multi-centre study. Patients received omeprazole 40 mg daily for 28 days and either clarithromycin 500 mg t.d.s. or placebo t.d.s. for the first 14 days. Patients underwent endoscopy before starting treatment, at 2 weeks, immediately after stopping treatment if unhealed at 2 weeks, and at 1, 6 and 12 months after the end of treatment, or at the recurrence of symptoms. Eradication of H. pylori, duodenal ulcer healing and ulcer recurrence were measured. RESULTS: One-hundred and fifty-four patients were recruited and randomized to omeprazole plus clarithromycin (n = 74) or to omeprazole plus placebo (n = 80). One month after treatment, H. pylori was eradicated in 57 of 69 (83%; 95% CI: 72-91%) patients receiving omeprazole plus clarithromycin, compared with 1 of 75 (1%; 95% CI: 0-7%) receiving omeprazole alone (P < 0.001). In patients receiving omeprazole plus clarithromycin the ulcer healed at 2 weeks in 83% (95% CI: 71-91%) and at 4 weeks in 100% (95% CI: 95-100%), compared with 77% (95% CI: 66-86%) and 97% (95% CI: 91-100%) in those given omeprazole plus placebo (N.S.). Ulcers recurred at 12 months in 6% (95% CI: 1-16%) of patients given omeprazole plus clarithromycin, compared with 76% (95% CI: 63-86%) of patients given omeprazole plus placebo (P < 0.001). The incidence of side-effects was similar in both treatment groups (38% with clarithromycin dual therapy and 29% with omeprazole plus placebo; P = 0.304). Ninety per cent of patients took at least 90% of their prescribed medication. CONCLUSIONS: Omeprazole plus clarithromycin dual therapy eradicated H. pylori in 83% of patients with duodenal ulcer and significantly decreased 12-month recurrence from 76% to 6%.

Adult↗