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Biomedical subjects

J N Baxter

Publications and source records attributed to J N Baxter.

At least 37 records · Page 2Linked to original sources
PubMed2000

Relationship of carotenoid and vitamins A and E with the acute inflammatory response in acute pancreatitis.

BACKGROUND: Inflammation and oxidative stress are believed to be important in the development of the systemic complications of acute pancreatitis. The fat-soluble vitamins A and E, and the carotenoids have antioxidant properties. The aim of this study was to assess the effect of acute pancreatitis on serum concentrations of vitamin antioxidants and to relate such changes to the degree of the inflammatory response. METHODS: Thirteen consecutive patients with predicted severe acute pancreatitis were compared with 26 matched healthy controls. Five patients developed severe acute pancreatitis and three of these died. Vitamin antioxidant and C-reactive protein (CRP) levels were measured daily for up to 7 days. RESULTS: Patients had significantly lower levels of antioxidants throughout the course of the study (P < 0.017). In patients there was a significant correlation between peak CRP and trough antioxidant levels (P < 0. 01). In patients with mild acute pancreatitis, the concentrations of retinol and beta-carotene at final review were significantly higher than those in patients with severe acute pancreatitis (P < 0.05). This coincided with a reduction in CRP level. CONCLUSION: In acute pancreatitis, circulating concentrations of vitamin antioxidants are reduced and are inversely related to the rise in CRP level.

Acute Disease↗
PubMed1998

Pharmacokinetics of octreotide in patients with cirrhosis and portal hypertension; relationship between the plasma levels of the analogue and the magnitude and duration of the reduction in corrected wedged hepatic venous pressure.

In healthy subjects octreotide is largely metabolised by the liver suggesting that the plasma half-life of the somatostatin analogue may be prolonged in patients with hepatic dysfunction. The aim of this study was therefore (a) to determine the pharmacokinetics of octreotide following its subcutaneous injection in 6 patients with cirrhosis and portal hypertension and (b) compare the magnitude and duration of the effects of intravenous administration of 250 micrograms somatostatin and 50 micrograms octreotide on corrected wedged hepatic venous pressure (WHVP) and to relate the findings to the plasma levels of the analogue 1 h after administration in 13 patients with cirrhosis and portal hypertension. Following subcutaneous administration of 50 micrograms octreotide the circulating half life (range 2.4 to 4.79 h) was prolonged whereas the clearance (range 2.101 to 4.775 L/h) was decreased compared to healthy controls. Intravenous bolus administration of 250 micrograms somatostatin or 50 micrograms octreotide resulted in a reduction in WHVP of approximately the same magnitude and duration despite appreciable quantities of the analogue in the blood 1 h after administration (1944 +/- 226 pg/ml). These results indicate that the circulating half-life of octreotide is prolonged in cirrhotics suggesting that the dosage regimens should be modified in such patients to avoid accumulation of the analogue in the blood which may result in undesirable side-effects or toxicity. Furthermore, since the magnitude and duration of the reduction in WHVP elicited by IV octreotide is similar to that observed with somatostatin, the analogue, like the native hormone, must be administered by continuous IV infusion to produce a sustained response and hence a therapeutic effect in the management of acute variceal bleeding.

Blood Pressure↗
PubMed1997

Randomised trial of octreotide for long term management of cirrhosis after variceal haemorrhage.

OBJECTIVE: To assess the efficacy of long term octreotide as adjuvant treatment to programmed endoscopic sclerotherapy after acute variceal haemorrhage in cirrhotic portal hypertension. DESIGN: Randomised clinical trial. SETTING: University hospital. SUBJECTS: 32 patients with cirrhotic portal hypertension. INTERVENTIONS: Programmed injection sclerotherapy with subcutaneous octreotide 50 micrograms twice daily for 6 months, or programmed injection sclerotherapy alone. MAIN OUTCOME MEASURES: Episodes of recurrent variceal bleeding and survival. RESULTS: Significantly fewer patients receiving combined octreotide and sclerotherapy had episodes of recurrent variceal bleeding compared with patients given sclerotherapy alone (1/16 v 7/16; P = 0.037, Fisher's exact test), and their survival was significantly improved (P < 0.02, log rank test); this improvement was maintained for 12 months after the end of the study. Combined treatment also resulted in a sustained decrease in portal pressure (median decrease -6.0 mm Hg, interquartile range -10 to -4.75 mm Hg, P = 0.0002) compared with sclerotherapy alone (median increase 1.5 mm Hg, interquartile range 0.25 to 3.25 mm Hg), as well as a significant improvement in liver function as assessed by plasma concentrations of bilirubin, albumin, and alanine aminotransferase and by hepatocyte metabolism of aminopyrine labelled with carbon-14. CONCLUSION: Long term octreotide may be a valuable adjuvant to endoscopic sclerotherapy for acute variceal haemorrhage in cirrhotic portal hypertension.

Acute Disease↗
PubMed1997

Randomized trial of different insufflation pressures for laparoscopic cholecystectomy.

BACKGROUND: The factors affecting cardiorespiratory changes and postoperative pain after laparoscopic cholecystectomy are poorly understood. The aim of this study was to assess these changes in patients undergoing laparoscopic cholecystectomy at an insufflation pressure of 7.5 or 15 mmHg. METHODS: Forty patients with similar preoperative characteristics were randomized, 20 to each group. RESULTS: There were no significant differences in intraoperative heart rate or cardiac index although the latter fell significantly soon after insufflation in both groups. The fall in cardiac index lasted longer (7 versus 2 min) and coincided with a slower rise in mean arterial pressure in those having 15 mmHg insufflation. Changes in peak airway pressure, end-tidal carbon dioxide and arterial blood gases were similar. After operation the low-pressure group had significantly less pain, better preservation of pulmonary function and were discharged home sooner (P = 0.015). CONCLUSIONS: Insufflation pressure significantly affects the haemodynamic changes and postoperative pain associated with laparoscopic cholecystectomy.

Carbon Dioxide↗
PubMed1997

Gastric emptying in patients with constipation following childbirth and due to idiopathic slow transit.

BACKGROUND: Idiopathic slow transit constipation (ISTC) is considered to be a heterogeneous condition in which patients have varying sites and degrees of delayed gastrointestinal transit. The majority of patients have pancolonic disease, and colectomy with ileocolorectal anastomosis has been the mainstay of surgical treatment. Severe constipation following traumatic childbirth is now being recognized and this subgroup of patients may have delayed transit confined to the rectosigmoid colon. In theory, proximal transit in these patients should be normal. METHODS: Gastric emptying was studied in patients with constipation following childbirth or ISTC and in controls. After an overnight fast, both patients and controls received breakfast, which consisted of cornflakes, sugar and milk. The liquid marker 111In-labelled di-ethylene tri-amine penta-acetic acid (DTPA) was added to the milk. A solid marker, 99mTc-labelled colloid, was impregnated on to paper and sealed with cellulose. The t1/2 for gastric emptying was calculated. RESULTS: Liquid phase emptying was normal in both constipation following childbirth and ISTC. Solid phase emptying was delayed significantly in ISTC compared with that in patients with constipation following childbirth and controls. In addition, half the patients with ISTC had delayed transit through the small bowel and proximal colon. Small bowel and colonic transit were normal in patients with constipation following childbirth. CONCLUSION: Patients with constipation following childbirth represent a distinct subgroup with normal proximal gastrointestinal function. Gastric emptying studies may be helpful in selecting patients for surgical management of severe constipation.

Adult↗
PubMed1997

Prospective placebo-controlled randomized trial of lexipafant in predicted severe acute pancreatitis.

BACKGROUND: Many patients with severe acute pancreatitis develop organ system failure during the first few days of illness, and this accounts for the majority of early deaths. No specific therapy is available and treatment remains supportive. METHODS: In a randomized controlled trial conducted in 11 hospitals in the West of Scotland, 50 patients with predicted severe acute pancreatitis were selected from 188 screened over a 14-month period. Patients received placebo or lexipafant, a potent platelet-activating factor antagonist, by continuous intravenous infusion at a dose of 100 mg/day for up to 7 days. Early systemic complications were assessed by the measurement of organ failure scores. RESULTS: There was a significantly greater fall in organ failure score in the treatment group during the 7 days of study (mean and median changes in organ failure score were 0.17 and 0 in the placebo group versus -1.42 and -1 in the treatment group; P = 0.003, Wilcoxon rank sum test), associated with trends towards a reduction in mortality and a reduced incidence of systemic complications. CONCLUSION: These results suggest that lexipafant may be a useful adjunct to full supportive care in the early management of patients with severe acute pancreatitis.

Acute Disease↗
PubMed1996

Increased monocyte cytokine production in association with systemic complications in acute pancreatitis.

Tumour necrosis factor (TNF) alpha, interleukin (IL) 1 beta, IL-6 and IL-8 are thought to play a central role in the pathophysiology of sepsis but their role in acute pancreatitis is unknown. In the present study, monocytes were isolated from the peripheral blood of 26 patients with moderate or severe acute pancreatitis without biliary sepsis. Secretion of these cytokines in vitro was measured at intervals during the first week of illness. Sixteen patients developed systemic complications. Peak TNF-alpha secretion was significantly higher in patients who developed systemic complications (median (interquartile range (i.q.r.)) 18.5 (5.5-28.5) ng/ml) than in those with an uncomplicated course (3.7 (2.3-6.4) ng/ml, P < 0.01). Similarly, peak IL-6 and peak IL-8 secretion were significantly higher in the complicated group (IL-6: complicated median (i.q.r.) 48.9 (12.1-71.0) ng/ml, uncomplicated 16.3 (14.2-37.9) ng/ml, P < 0.05; IL-8: complicated 748 (643-901) ng/ml, uncomplicated 608 (496-749) ng/ml), P < 0.05). No significant difference in peak IL-1 beta secretion was observed between the two groups. Systemic complications of acute pancreatitis are associated with a significant increase in monocyte secretion of TNF-alpha, IL-6 and IL-8 suggesting that, as in sepsis, these cytokines play a central role in the pathophysiology of the disease.

Acute Disease↗
PubMed1996

The use of lexipafant in the treatment of acute pancreatitis.

The pathophysiology of systemic organ failure in acute pancreatitis has been the subject of debate for many years but there is growing evidence that increase production of pro-inflammatory cytokines plays an important role. from this work and from the results of studies in experimental pancreatitis there exists a rationale for the use of PAF antagonists in the treatment of acute pancreatitis. Two pilot studies have now demonstrated a beneficial effect of the PAF antagonist Lexipafant on acute pancreatitis which may lead to an important advance in the treatment of these patients. A multicentre trial aiming to recruit 300 patients with severe acute pancreatitis is now underway in the UK, the results of which will be awaited with interest.

Acute Disease↗
PubMed1996

Early outcome after open versus extraperitoneal endoscopic tension-free hernioplasty: a randomized clinical trial.

BACKGROUND: The use of minimal access surgery for repair of groin hernias is controversial. The aim of this study was to compare endoscopic tension-free hernia repair with open tension-free hernia repair within a randomized clinical trial. METHODS: One hundred twenty patients were randomized by four surgeons during a 1-year period. Early outcome measures were then analyzed by intention to treat. RESULTS: Median postoperative pain scores (63 [interquartile range (IQR), 23 to 81] versus 35 [IQR, 17 to 62]; p = 0.004) and analgesia requirements (2.5 [IQR, 2 to 4] doses verus 2.0 [IQR, 1 to 3] doses; p = 0.0008) were significantly less for patients undergoing endoscopic hernia repair. Hospital stay (1 [IQR, 0 to 1] day versus 2 [IQR, 1 to 2] days; p < 0.0001) was also significantly reduced for the endoscopic group. Wound complications occurred significantly more frequently in the open group. No difference in pulmonary function or metabolic response to trauma (interleukin-6, C-reactive protein, glucose, albumin) was observed between the groups. CONCLUSIONS: This study shows significant short-term advantages for endoscopic tension-free repair over open tension-free repair. However, larger studies with a longer follow-up period are required to establish the relative merits of both procedures in the management of patients with groin hernias.

Aged↗
PubMed1996

Mononuclear phagocyte activation and acute pancreatitis.

Severe, acute pancreatitis is commonly associated with a systemic illness which may result in multiple organ failure. There is evidence that an aberrant immune response, involving increased secretion of proinflammatory cytokines from activated monocytes and mononuclear phagocytes, is responsible for another systemic illness--septic shock. Previous studies have investigated whether there is a correlation between plasma cytokine levels and severity of pancreatitis. However, these results may not reflect mononuclear phagocyte activation. In this paper, monocytes (collected from patients with severe pancreatitis) were cultured in vitro and secreted cytokine levels measured after 24 hours by ELISA. Secretion of tumour necrosis factor alpha, interleukin-6 and interleukin-8 was higher in cells taken from patients who later developed systemic complications. There was no difference in the secretion of interleukin-1 beta. The mechanism by which mononuclear phagocytes are activated in acute pancreatitis, and the role of genetic predisposition, are discussed.

Acute Disease↗
PubMed1995

Bile duct injury and bile leakage in laparoscopic cholecystectomy.

The introduction of laparoscopic cholecystectomy has been associated with an increased incidence of bile duct injury. This review presents the incidence of bile duct injury in reported series and examines the role of the learning curve and other contributing factors. There is good evidence to suggest that, with adequate training and experience, the incidence of biliary injury can be reduced to a level comparable to that of open cholecystectomy. Continued audit is required to ensure that the low complication rates achieved in selected centres with wide experience are reproduced by the surgical community in general.

Bile↗
PubMed1995

Symptomatic outcome 1 year after laparoscopic and minilaparotomy cholecystectomy: a randomized trial.

In a randomized controlled trial, 299 patients were sent a symptoms questionnaire 1 year after laparoscopic (n = 151) or minilaparotomy (n = 148) cholecystectomy for symptomatic cholelithiasis. The response rate to the questionnaire from contactable patients was 86 per cent. In both groups, at least 90 per cent of patients reported that their symptoms were improved, and at least 93 per cent rated the success of their operation as 'excellent', 'good', or 'fair'. However, over half the patients reported abdominal pain, a quarter reported flatulence, and a quarter dyspepsia. The only difference between treatment groups was that a higher proportion of patients who underwent minilaparotomy reported heartburn (35 per cent versus 19 per cent, P = 0.005). Patients who reported a 'poor' outcome were more likely to have suffered a postoperative complication, had lower quality of life scores, and higher anxiety and depression scores. Both laparoscopic and minilaparotomy cholecystectomy result in symptomatic benefit in at least 90 per cent of patients with symptomatic cholelithiasis.

Abdominal Pain↗
PubMed1995

Effect of extraperitoneal carbon dioxide insufflation on intraoperative blood gas and hemodynamic changes.

Carbon dioxide pneumoperitoneum has been shown to produce respiratory and hemodynamic changes due to both CO2 absorption and the effects of increased intraperitoneal pressure. We have measured the blood gas, end-tidal CO2, and hemodynamic changes produced during extraperitoneal CO2 insufflation (n = 22). These have been compared with the changes occurring during CO2 pneumoperitoneum (n = 11) under standardized anesthetic conditions. The changes observed during pneumoperitoneum were consistent with previous descriptions. There was a median rise in arterial pCO2 of 1 kPa over the first 15-20 min, followed by a second phase of only gradual change. There was also an increase in mean arterial pressure of 18 mmHg during the insufflation period. We have found a similar magnitude of rise in arterial pCO2 during extraperitoneal insufflation (median 0.83 kPa), but the rate of rise was significantly slower (P < 0.05). In addition, there was no change in the mean arterial pressure during extraperitoneal insufflation. Our results suggest that extraperitoneal CO2 insufflation may be safer than CO2 pneumoperitoneum in patients with preexisting cardiorespiratory disease.

Adult↗
PubMed1995

Fluctuations in the secretion of pancreatic enzymes between consecutive doses of octreotide: implications for the management of fistulae.

OBJECTIVE: To determine whether variations in pancreatic enzyme secretion between consecutive subcutaneous administrations of octreotide explain why octreotide takes longer than somatostatin to facilitate the closure of gastrointestinal fistulae. METHODS: Pancreatic enzyme secretion was studied over a 3-day period in a patient with a catheter left in the pancreatic duct postoperatively. On days 1 and 3 the patient did not receive octreotide (control days) but on day 2 he received subcutaneous octreotide 100 micrograms every 8 h. Pancreatic juice was collected at 2-h intervals over the 3-day period. RESULTS: On the day of octreotide treatment, the patient's pancreatic secretory volume and protein output were significantly reduced (P < 0.001, Mann-Whitney U-test) compared with the 2 control days. The pancreatic secretory volume decreased markedly after the first injection of octreotide and remained low for the duration of the treatment period. The enzyme concentration of the pancreatic juice was also markedly reduced after the first injection of octreotide. However, approximately 4h after each octreotide injection the protein concentration of the pancreatic juice began to rise progressively, peaking approximately 6h after each administration of the analogue. CONCLUSION: Subcutaneous administration of octreotide produces a sustained decrease in the volume of pancreatic juice secreted, but enzyme secretion rises progressively between consecutive administrations of the analogue. The net effect is therefore the production of low volumes of pancreatic juice with a high enzyme concentration between consecutive injections of octreotide, which may delay the healing of the fistula tract. This may explain why longer treatment periods are required to achieve fistula closure with octreotide than with somatostatin, particularly in the case of pancreatic fistulae.

Humans↗
PubMed1994

Laparoscopic versus minilaparotomy cholecystectomy: a randomised trial.

Although laparoscopic cholecystectomy has rapidly become routine practice in the UK, there has been no rigorous comparison of it with open cholecystectomy. In our trial, 302 patients were randomised to laparoscopic or minilaparotomy cholecystectomy. Recovery after surgery was assessed by length of hospital stay, outpatient review at 10 days and 4 weeks, and patient questionnaires 1, 4, and 12 weeks after surgery. The mean operation time was 14 min shorter for minilaparotomy, while median post-operative hospital stay was 2 days shorter after laparoscopic cholecystectomy. The hospital costs were about 400 pounds greater for the laparoscopic procedure. Laparoscopic patients returned to work in the home sooner; at 1 week, they had better physical and social functioning, were less limited by physical problems, and had less pain and depression. At 4 weeks, only physical functioning and depression scores were better in the laparoscopic group, and by 3 months there were no differences. Laparoscopic patients were more satisfied with the appearance of their scars. The incidence of complications after both procedures was 20%. Compared to minilaparotomy cholecystectomy, laparoscopic cholecystectomy results in shorter hospital stay, less postoperative dysfunction, and quicker return to normal activities, but is more costly.

Activities of Daily Living↗