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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
PubMed1999

A combination of ciprofloxacin and Rowachol does not prevent biliary stent occlusion.

BACKGROUND: Endoscopic insertion of biliary prostheses is now an established palliative treatment for frail and elderly patients with distal extrahepatic malignant biliary strictures who are unable to tolerate major surgery. The major limitation to long-term biliary stenting is late stent occlusion caused by bacterial adherence followed by encrustation with amorphous bacterial products. We studied the effect on the duration of stent patency of combination therapy with ciprofloxacin and Rowachol, a choleretic agent, in a group of patients who underwent stent insertion for extrahepatic malignant biliary strictures. METHODS: Patients with this diagnosis were randomized to either active treatment with ciprofloxacin (500 mg twice daily) and Rowachol (2 tablets 3 times daily) or no drug treatment (control group). They were followed up prospectively and the end points of the study were stent occlusion and patient survival. RESULTS: Forty-eight patients who had successful stent placement were recruited; 8 patients were excluded from the final analysis because of death in less than 1 month (5 patients) or stent replacement within a month because of persistent jaundice (3 patients). Twenty patients were randomized to the active and control groups. One patient in the active group withdrew because of nausea. The 2 groups were comparable with regard to age, gender, causes of extrahepatic malignant biliary strictures, and levels of serum alkaline phosphatase and bilirubin. There were significant reductions in mean serum bilirubin and alkaline phosphatase concentrations 1 month after stent placement. At the time of analysis, 12 patients were still alive (7 patients from the control group). Median survival was 23 weeks in both the active treatment group and the control group. There were 9 episodes (45%) of stent occlusions in the active treatment group and 10 episodes (50%) in the control group. The median time to stent occlusion was 23 (range 7 to 68) weeks for the active treatment group and 21 (range 6 to 56) weeks for the control group, p = 0.23. There was no significant difference in the duration of patient survival and of stent patency between the 2 groups. The lack of difference between treated and untreated patients in survival duration and stent patency was also shown if the results were analyzed on an intent-to-treat basis and the 8 patients who were excluded in the final analysis were also analyzed. CONCLUSIONS: Prophylactic therapy with ciprofloxacin and Rowachol does not prolong stent patency or patient survival.

Aged↗
PubMed1999

The effect of octreotide on gastroduodenal blood flow measured by laser Doppler flowmetry in rabbits and man.

OBJECTIVE: The somatostatin analogue, octreotide is valuable in the management of variceal bleeding, and it has been suggested that it may stop peptic ulcer hemorrhage by reducing gastroduodenal blood flow or increasing intragastric pH. The aim of this study was to determine the effect of intravenous octreotide infusion on gastroduodenal mucosal blood flow and gastric pH. METHODS: Seven New Zealand white rabbits and five healthy human volunteers were used. Mucosal blood flow was measured using a laser Doppler flowmeter (LDF). The Doppler probe was positioned in the upper gastrointestinal tract of the seven rabbits and five human volunteers. Blood flow was measured before and after octreotide infusion. RESULTS: In the animal experiments, mucosal blood flow was decreased in a dose dependent manner in the gastric body (209.1-56.3 U) (p < 0.008), antrum (143.3-33.3 U) (p < 0.02) and duodenum (254-67.6 U) (p < 0.016) by doses of octreotide ranging from 10-50 microg/kg of body weight. In the human studies, mucosal blood flow was decreased in the gastric body (p < 0.016) and antrum (p < 0.009) after octreotide infusion (dose 1-1.5 microg/kg). Intragastric pH was significantly increased (p < 0.05). The change was not associated with systemic hemodynamic changes. CONCLUSIONS: Gastroduodenal mucosal blood flow was reduced and intragastric pH increased by octreotide. This agent could be helpful in the management of gastroduodenal mucosal bleeding.

Adult↗
PubMed1998

Nitric oxide and gall-bladder motor function.

BACKGROUND: The L-arginine: nitric oxide (NO) pathway has been shown to be important in the regulation of intestinal motility and NO may be the mediator for nonadrenergic noncholinergic (NANC) neurotransmission. AIM: To determine the role of the L-arginine: NO pathway in gall-bladder motor function. METHODS: Strips of fresh bovine and human gall-bladders were stimulated with cholecystokinin (CCK). The effects of glyceryl trinitrate (GTN), sodium nitroprusside and Kreb's solution upon CCK-stimulated muscle contraction were examined. The effect of the NO synthase inhibitor, L-NG-monomethyl-arginine (L-NMMA) upon basal muscle tone was also examined. Ten human gall-bladders were immunohistochemically stained for nitric oxide synthase (NOS) and product 9.5 to identify neurones. Postprandial gall-bladder emptying was measured on separate occasions in six healthy volunteers during systemic intravenous infusion of normal saline; glyceryl trinitrate; sodium nitroprusside (SNP), hydralazine and L-NMMA. RESULTS: In the in vitro study, GTN and SNP significantly reduced the tension of CCK-stimulated muscle contraction whilst Kreb's solution had no effect. L-NMMA increased tonic and phasic muscle contractions. Immunohistochemical staining for NOS was consistently absent in human gall-bladders. In the in vivo study, both GTN and SNP caused significant impairment of gall-bladder emptying; the ejection fraction was only 50% at the end of the study period involving these infusates, this contrasted with ejection fractions in excess of 80% during infusions with hydralazine, saline and L-NMMA. CONCLUSION: Pharmacological doses of NO donors impair postprandial gall-bladder emptying in vivo and relax gall-bladder smooth muscle in vitro. However, negative immunohistochemical staining suggest NOS is unlikely to be the neurotransmitter for NANC innervation regulating gall-bladder motility.

Adult↗
PubMed1998

Caroli's disease.

Caroli's disease is characterized by multifocal segmental dilatation of the intrahepatic bile ducts. It is a rare congenital condition, which appears to be autosomal recessively inherited in most cases. There are two forms of disease, one associated with congenital hepatic fibrosis and a simple form occurring alone. Recent reports suggest that the simple form may be as common as that with congenital hepatic fibrosis. Other conditions, including choledochal cyst and renal cystic disease, are frequently associated. The major clinical feature is recurrent cholangitis, which may be complicated by intrahepatic calculi and hepatic abscess formation. There is good evidence that malignancy complicates Caroli's disease in approximately 7% of cases. The diagnosis rests on demonstrating that the cystic liver lesions are in continuity with the biliary tree. Modern imaging techniques allow the diagnosis to be made more easily and without invasive imaging of the biliary tree. The treatment depends on the clinical features and the location of the biliary abnormality. When the disease is localized to one hepatic lobe, hepatectomy relieves symptoms and appears to remove the risk of malignancy. In diffuse Caroli's disease, treatment options include conservative or endoscopic therapy, internal biliary bypass procedures and liver transplantation in carefully selected cases.

Caroli Disease↗
PubMed1998

Appendicectomy and ulcerative colitis.

The aetiology of ulcerative colitis (UC) is unknown. However, much interest has been devoted recently to the relationship between appendicectomy and ulcerative colitis. A case-control study was conducted, comparing appendicectomy rates between 110 patients with UC (group 1) and 136 patients attending an orthopaedic clinic free from UC (group 2). The appendicectomy rates were 0.9% (group 1) and 10.3% (group 2), respectively (P < 0.002). The present study shows that patients with ulcerative colitis had rarely undergone appendicectomy before the first manifestation of colitis. Further research on this relationship is called for.

Adolescent↗
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↗