PubMed Health⌕ Search

Biomedical subjects

S A Jenkins

Publications and source records attributed to S A Jenkins.

At least 19 recordsLinked to original sources
PubMed1998

Poly[di(carboxylatophenoxy)phosphazene] (PCPP) is a potent immunoadjuvant for an influenza vaccine.

The adjuvant activity of poly[di(carboxylatophenoxy)phosphazene] (PCPP) on the immunogenicity of formalin-inactivated influenza virions and commercial trivalent influenza vaccine was studied. Regardless of which antigen preparation is used, the addition of 100 micrograms PCPP enhances the HAI antibody response 10-fold over the levels elicited by the vaccine alone. Similarly, PCPP enhanced the IgM, IgG, and IgG1 ELISA antibody titers to influenza antigens at least 10-fold higher than the vaccine alone. In contrast, the IgG2a isotype titers were only enhanced about 2-fold. Immunization of aged mice (22 months old) with trivalent influenza vaccine alone did not sero-convert these mice as measured by HAI or ELISA whereas significant sero-conversion was achieved when mice were immunized with PCPP-formulated trivalent vaccine. The adjuvant activity of PCPP was shown to not be due to a site of injection depot effect. PCPP adjuvanticity was positively correlated to the molecular weight of the polymer.

Adjuvants, Immunologic↗
PubMed1998

Development of analogues: successes and failures.

The search for new pharmaceutical treatments has led to the isolation of products from a range of natural sources. Analogues synthesized from these products may possess an improved therapeutic effect over their natural counterparts. Two natural peptides, vasopressin and somatostatin, possess pronounced in vivo effects, so do their analogues terlipressin and octreotide. Vasopressin is a powerful vasopressor, reducing portal pressure, and has been used to treat gastrointestinal haemorrhages. However, a number of adverse cardiovascular effects resulting from an increase in peripheral vascular resistance have been associated with this drug. Terlipressin, however, is more effective, has an improved safety profile and is associated with fewer side effects than vasopressin. Somatostatin, a growth regulatory hormone, achieves haemostasis by decreasing splanchnic blood flow, and is effective in preventing early rebleeding. Somatostatin is effective in treating bleeding oesophageal varices (BOV) and is associated with fewer and more transient side effects than terlipressin. Octreotide, however, has greater stability and a longer half-life than somatostatin, but has a less favourable safety profile. Octreotide displays a number of therapeutic advantages over somatostatin, but not in the treatment of gastrointestinal indications. The development of terlipressin from vasopressin has demonstrated a number of clinical advantages, while the development of octreotide from somatostatin has not shown any significant advantage in the treatment of BOV.

Esophageal and Gastric Varices↗
PubMed1998

PCPP as a parenteral adjuvant for diverse antigens.

The adjuvanticity of the phosphazene polymer, poly[di(carboxylatophenoxy) phosphazene] (PCPP) was examined with a diverse collection of immunogens. PCPP proved to be a potent adjuvant for trivalent influenza virus vaccine, tetanus toxoid, hepatitis B surface antigen, herpes simplex virus glycoprotein gD2 and the capsular polysaccharide, polyribosylribitolphosphate, from Haemophilus influenzae type b. Taken together these results clearly demonstrate the general utility of PCPP as an adjuvant. Furthermore, PCPP was a superior adjuvant at least with TT compared to similar negatively charged polyanions, polymethylacrylic acid and polyacrylic acid.

Acrylates↗
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

Effects of octreotide on liver regeneration and tumour growth in the regenerating liver.

The ability of the liver to regenerate following resection is remarkable. However, there is evidence to suggest that tumour growth within the regenerating liver is significantly increased. As octreotide (a synthetic analogue of somatostatin) inhibits the growth and development of hepatic tumour in rats, we have investigated its effects on liver regeneration, liver blood flow, hepatic reticuloendothelial system activity and tumour growth in the rat following partial hepatectomy (PH). Octreotide significantly inhibited liver regeneration in the rat 1 and 2 weeks following PH when compared with controls (regeneration index: 1.0 and 1.14 cf. 1.14 and 1.4, respectively). There was no significant difference in hepatic arterial or portal venous blood flow following PH in control or octreotide-treated rats. However, portal pressure was significantly reduced in octreotide-treated rats. Hepatic reticuloendothelial system activity was significantly increased in octreotide-treated rats compared with control animals 1 and 2 weeks after hepatectomy (uptake of radiolabelled technetium-99m albumin colloid: 2.2 and 3.9 cf. 1.6 and 1.9). The growth of both HSN (fibrosarcoma) and K12-Tr (colonic adenocarcinoma) cells in the regenerating liver was significantly decreased by octreotide treatment compared with controls (median percentage hepatic replacement: HSN control 71.3%, Octreotide 8.4%, K12-Tr Control 38.3%, Octreotide 4.5%). The results of the present study demonstrate that octreotide inhibits both liver regeneration and tumour growth following PH, possibly via a similar mechanism.

Animals↗
PubMed1997

A multicentre randomised trial comparing octreotide and injection sclerotherapy in the management and outcome of acute variceal haemorrhage.

BACKGROUND: Few studies have compared vasoactive drugs with endoscopic sclerotherapy in the control of acute variceal haemorrhage. Octreotide is widely used for this purpose, but its value remains undetermined. AIMS: To compare octreotide with endoscopic sclerotherapy for acute variceal haemorrhage. PATIENTS: Consecutive patients with acute variceal haemorrhage. METHODS: Patients were randomised at endoscopy to receive either a 48 hour intravenous infusion of 50 pg/h octreotide (n = 73), or emergency sclerotherapy (n = 77). RESULTS: Overall control of bleeding and mortality was not significantly different between octreotide (85%, 62 patients) and sclerotherapy (82%, 63 patients) over the 48 hour trial period (relative risk of rebleeding 0.83; 95% confidence interval (CI) 0.38 to 1.82), irrespective of Child's grading or active bleeding at endoscopy. One major complication was observed in the sclerotherapy group (aspiration) and two in the octreotide group (pulmonary oedema, severe paralytic ileus). During 60 days of follow up there was an overall trend towards an increased mortality in the octreotide group which was not statistically significant (relative risk of dying at 60 days 1.91, 95% CI 0.97 to 3.78, p = 0.06). CONCLUSIONS: The results of this study indicate that intravenous octreotide is as effective as injection sclerotherapy in the control of acute variceal bleeding, but further controlled trials are necessary to evaluate the safety of this treatment.

Acute Disease↗
PubMed1996

Increasing hepatic arterial flow to hypovascular hepatic tumours using degradable starch microspheres.

The effect of degradable starch microspheres (DSM) on the intrahepatic distribution of a low molecular weight marker, 99Tcm-labelled methylene diphosphonate (MDP), was studied in rats with hypovascular HSN liver tumours. MDP was injected regionally, via the hepatic artery, alone or co-administered with DSM, with or without subsequent occlusion of either the hepatic artery or the portal vein. Tumour vascularity was measured with 57Co-labelled microspheres. Co-injection with DSM immediately significantly increased hepatic retention of marker in both tumour (T) (median 22.40 (range 16.82-39.58)% injected dose) and normal liver (N) (9.08 (4.85-12.59) %ID) the greater effect seen in T (P < 0.01). After DSM degradation, very little MDP remained in N (0.61 (0.28-1.40) %ID) but there was significant retention in T (10.01 (6.73-20.28) %ID, P < 0.01). Clamping the hepatic artery had minimal effect on the retention of MDP when administered alone. Regional injection of 16.5 microM 57Co microspheres resulted in a N:T ratio of 2.25:1. Concomitant injection of the 40 microM DSM was 57Co microspheres reversed this ratio to 1:2. The results indicate that DSM selectively enhances the retention of MDP to a hypovascular hepatic tumour, not by causing intra-tumour stasis, but by directing a greater arterial flow to hypovascular areas in the liver.

Animals↗
PubMed1996

The role of an advanced thermotherapy device in prostatic voiding dysfunction.

OBJECTIVES: To investigate the efficacy of an advanced transurethral thermotherapy (TUMT) device (T3, Urologix) using urodynamic analysis in addition to the standard evaluation protocol in patients with symptomatic benign prostatic hyperplasia (BPH). PATIENTS AND METHODS: Fifty men with symptomatic BPH were assessed using the AUA symptom score, uroflowmetry and ultrasonography (to determine prostatic volume and residual urinary volume) before and 6 weeks, 3, 6 and 12 months after thermotherapy. TUMT was delivered using a focused microwave energy system for 1 h in each patient, treated on an out-patient basis. Video pressure flow studies with advanced urodynamic analysis were also performed before and 3 months after treatment. RESULTS: The mean AUA symptom score decreased by 63%, the mean peak flow rate increased by 64% and the post-void residual volume decreased by 30% 3 months after treatment; this improvement was maintained at one year after treatment. Advanced urodynamic analysis showed that 52% of the patients had a decreased severity of obstruction. Furthermore, the efficiency of detrusor contraction improved in 86% of the patients. The improvement in the symptom score, flow rate and residual urine was significantly better in patients with marginal obstruction than in patients with unequivocal obstruction. CONCLUSION: Urodynamic analysis can predict the treatment outcome of TUMT and the results of thermotherapy are significantly better in patients with marginal prostatic bladder outflow obstruction.

Aged↗
PubMed1996

Progressive disruption of acinar cell calcium signaling is an early feature of cerulein-induced pancreatitis in mice.

BACKGROUND & AIMS: Disruption of pancreatic exocrine secretion is an important feature of acute pancreatitis. Because cytosolic calcium is a key intracellular messenger controlling pancreatic secretion, this study examined patterns of calcium signaling during the early stages of cerulein-induced pancreatitis. METHODS: Mice were administered hourly intraperitoneal injections of cerulein (50 micrograms/kg), and paired controls were administered saline. Acini were isolated by collagenase from pancreatic tissue harvested after injections 1, 3, 5, and 7 and were loaded with Fura-2. Individual cellular calcium responses to acetylcholine and cholecystokinin were studied using digital imaging. RESULTS: The proportion of cells maintaining a normal oscillatory calcium response to physiological secretagogue stimulation diminished progressively after increasing cerulein injections. Also, the normal polarized spatial pattern of calcium Increase within individual acinar cells was progressively lost. A sustained response to high-dose stimulation was maintained but with diminishing amplitude. The characteristic calcium response to the Ca(2+)-adenosine triphosphatase inhibitor thapsigargin was maintained, implying that calcium reuptake and extrusion were not impaired. CONCLUSIONS: Progressive disruption of physiological patterns of pancreatic acinar cell calcium signaling, notably in the secretory pole of the cell, is an early feature of pancreatitis induced by cerulein hyperstimulation. These changes may be important in contributing to the disruption of exocrine secretion in acute pancreatitis.

Acetylcholine↗
PubMed1996

Therapeutic potential of octreotide in the treatment of liver metastases.

Octreotide is a synthetic analogue of somatostatin that has clear inhibitory effects on the growth of many animal and human cell lines, including colorectal cell lines both in vitro and in vivo. Colorectal cancer metastatic to the liver is clinically important, both in terms of the number of patients affected and the lack of any effective treatment for the majority of patients. Octreotide inhibits the growth of colorectal liver tumour in a number of experimental models and, in at least three tumour types, inhibits the growth of established micro-metastases. The precise mechanism of action is not known. However, the drug is likely to be most beneficial in the treatment of liver metastases when the tumour burden is relatively small. The available evidence, although experimental, suggests that octreotide may also have a beneficial effect on the development of liver metastases when used as an adjuvant to surgery in colorectal cancer and this area warrants urgent clinical investigation. The cytotoxics which are currently used as an adjuvant to surgery for colorectal cancer have unpleasant side effects which can be life-threatening. There will also be a proportion of patients who have undergone a truly curative resection of their tumour and will thus be treated unnecessarily. The potential benefits of octreotide in the adjuvant setting, although promising, remain speculative, but octreotide has an acceptably low incidence of side effects and can be administered safely for a prolonged period of time.

Animals↗
PubMed1996

Octreotide in the control of post-sclerotherapy bleeding from oesophageal varices, ulcers and oesophagitis.

Bleeding from oesophageal varices, oesophageal ulcers or oesophagitis is occasionally massive and difficult to control. Octreotide, a synthetic analogue of somatostin lowers portal pressure and collateral blood flow including that through varices, increases lower oesophageal sphincter pressure, and inhibits the gastric secretion of acid as well as pepsin. Our current experience suggests it is effective in controlling acute variceal haemorrhage. Therefore we have examined the efficacy of octreotide in the control of post-sclerotherapy bleeding from oesophageal varices, oesophageal ulcers and oesophagitis. During the study period 77 patients experienced a significant gastrointestinal bleed (blood pressure < 100 mm Hg, pulse > 100 beats per min or the need to transfuse 2 or more units of blood to restore the hemoglobin level) following injection sclerotherapy of oesophageal varices. The source of bleeding was varices in 42 patients, oesophageal ulcers in 31 and oesophagitis in 4. All patients received a continuous intravenous infusion of octreotide (50 micrograms/h) for between 40-140h. If bleeding was not controlled in the first 12h after commencing octreotide hourly bolus doses (50 micrograms) for 24h were superimposed on the continuous infusion. Haemorrhage was successfully controlled by an infusion of octreotide in 38 of the 42 patients with bleeding from varices, in 30 of 31 patients with oesophageal ulceration, and all patients with oesophagitis. In the 1 patient with persistent bleeding from oesophageal ulceration and in 2 of the 4 with continued haemorrhage from varices, haemostasis was achieved by hourly boluses of 50 micrograms octreotide for 24h in addition to the continuous infusion. No major complications were associated with octreotide administration. The results of this study clearly indicate that octreotide is a safe and effective treatment for the control of severe haemorrhage after technically successful injection of sclerotherapy.

Adult↗
PubMed1996

Abnormalities of gastric emptying in portal hypertension.

OBJECTIVES: To investigate: 1) the rate of gastric emptying of portal hypertensive patients and 2) whether alterations in gastric emptying play any role in the development of portal hypertensive gastropathy. METHODS: Fifty patients (37 with esophageal varices) with cirrhosis and seven with extrahepatic portal hypertension underwent upper GI endoscopy followed by radionuclide gastric emptying studies using a semi-solid meal. Twenty-six patients also under went corrected wedged hepatic venous pressure measurement. Sixteen normal subjects underwent gastric emptying studies only. RESULTS: Varices were completely obliterated by sclerotherapy in 17 patients and were patent in 27. Thirty-seven patients had portal hypertensive gastropathy, 25 of whom had mild changes and 12 severe. No significant difference in gastric emptying was observed between patients with mild and severe portal hypertensive gastropathy and between those with portal hypertensive gastropathy and a normal gastric mucosa. There was no significant difference in gastric emptying between normal subjects and portal hypertensive patients although the latter group showed a tendency for faster gastric emptying. No difference in the rate of gastric emptying was observed between portal hypertensive patients with intrahepatic and extrahepatic pathology. However, patients with esophageal varices (patent and obliterated) emptied their stomachs significantly faster than those without (p = 0.01). There was no correlation between the rate of gastric emptying and corrected wedged hepatic venous pressure. CONCLUSIONS: It would appear that, although alterations in gastric emptying are common in portal hypertension, gastric emptying does not appear to play a causative role in the mucosal changes characteristic of portal hypertensive gastropathy.

Analysis of Variance↗
PubMed1996

The effects of Helicobacter pylori colonization on gastric function and the incidence of portal hypertensive gastropathy in patients with cirrhosis of the liver.

OBJECTIVES: To investigate the prevalence of Helicobacter pylori infection in 50 cirrhotic patients with biopsy-proven cirrhosis with and without portal hypertensive gastropathy and to study whether or not the effects of H. pylori colonization of the stomach on gastric acid and pepsin secretion, serum gastrin and pepsinogen I levels, gastric mucus, and gastric emptying contributed to the development of portal hypertensive gastropathy in cirrhotics. METHODS: All patients underwent an upper GI endoscopy followed by determination of basal and pentagastrin and insulin-stimulated gastric acid and pepsin secretion and serum gastrin and pepsinogen I levels. The gastric biopsies were stained to detect H. pylori infection, portal hypertensive gastropathy, and gastritis. The amount of gastric mucus was estimated by a microanalytical technique. The rate of gastric emptying was assessed by the radionuclide method using a semi-solid meal. RESULTS: Thirty-three (66%) patients had endoscopic evidence of portal hypertensive gastropathy, 10 with the severe (20%) and 23 with mild form (46%). Twenty (40%) patients had histological evidence of H. pylori infection. Eleven out of 33 (33%) patients with endoscopic portal hypertensive gastropathy had microscopic evidence of H. pylori infection. Eighteen out of 20 (90%) patients with chronic active gastritis had concomitant H. pylori colonization. In contrast, the gastric mucosa was histologically normal in 21 of the 30 patients (70%) not infected with H. pylori. Marked hypochlorhydria and reduced pepsin secretion associated with a tendency to hypergastrinemia were observed in cirrhotic patients colonized with H. pylori compared with those without. However, there was no significant difference in serum pepsinogen I concentrations, the ratio of polymeric to degraded gastric mucus, or the rate of gastric emptying between cirrhotics with and without H. pylori colonization of the stomach. Furthermore, these parameters were not significantly different in patients with portal hypertensive gastropathy with and without H. pylori infection. CONCLUSION: These observations suggest that H. pylori infection is unlikely to be involved in the pathogenesis of portal hypertensive gastropathy.

Adolescent↗
PubMed1996

Quantification of voiding dysfunction in patients awaiting transurethral prostatectomy.

PURPOSE: We investigated the role of advanced urodynamic analysis in the diagnostic evaluation for transurethral resection of the prostate. MATERIALS AND METHODS: A total of 62 consecutive patients awaiting transurethral resection of the prostate with the American Urological Association symptom score of more than 12, peak flow rate less than 13 ml. per second and significant residual urine underwent routine video pressureflow studies with advanced urodynamic analysis to quantify outflow function. Postoperative outcome was assessed at 3 months by symptom scores, uroflowmetry and ultrasonography (residual urine). RESULTS: The parameters used in the diagnostic evaluation for transurethral resection of the prostate did not correlate with urodynamic diagnosis of unequivocal obstruction. Weak detrusor contractility (without significant obstruction) accounted for voiding dysfunction in 50% of the patients. The results of transurethral resection of the prostate were significantly better in patients with unequivocal compared to equivocal obstruction. Furthermore, patients with unequivocal obstruction but weak detrusor contractility had a significantly poorer treatment outcome. CONCLUSIONS: Advanced urodynamic analysis in the diagnostic evaluation of patients with symptomatic benign prostatic hyperplasia can predict treatment outcome and, therefore, allows the urologist to choose the most appropriate therapeutic option for individuals.

Aged↗
PubMed1995

Is an elevated concentration of acinar cytosolic free ionised calcium the trigger for acute pancreatitis?

The pathogenesis of acute pancreatitis is poorly understood, despite well-recognised precipitating factors. Current evidence suggests that the earliest abnormalities of acute pancreatitis arise within acinar cells, but the key intracellular trigger has yet to be identified. Within the pancreas, physiological concentrations of secretagogues bind to G-protein-linked cell-surface receptors on acinar cells, evoking short, oscillatory spikes of acinar cytosolic-free ionised calcium ([Ca2+]i), an ubiquitous intracellular messenger. Specific effects within acinar cells include initiation of enzyme release through the phosphorylation cascades of stimulus-secretion coupling. Low resting levels of [Ca2+]i are restored by Ca(2+)-ATPase, which pumps calcium into the endoplasmic reticulum and out of the cell. If high concentrations of [Ca2+]i persist, toxicity results, intracellular signalling is disrupted, and cell damage occurs. Sustained elevations in acinar [Ca2+]i result from exposure to high concentrations of secretagogues, high doses of which also induce acute pancreatitis. Similarly, sustained elevations of [Ca2+]i may result from ductal hypertension, alcohol, hypoxia, hypercalcaemia, hyperlipidaemia, viral infection, and various drugs--all factors known to precipitate acute pancreatitis. We suggest that these factors precipitate acute pancreatitis by causing either excessive release of acinar [Ca2+]i, or damage to the integrity of mechanisms that restore low resting levels of [Ca2+]i, and that the consequent calcium toxicity is the key trigger in the pathogenesis of acute pancreatitis.

Acute Disease↗
PubMed1995

Octreotide inhibits the growth and development of three types of experimental liver metastases.

A study was performed to assess the effects of octreotide on the growth and development of liver metastases in rats. Tumour was induced by intraportal injection of three tumorigenic cell lines (the fibrosarcoma HSN and colonic adenocarcinomas K12/Tr and WB2054M) in syngeneic rats. Octreotide treatment (2 micrograms subcutaneously for 3 or 4 weeks) was started 18 h and 1 week after tumour induction; a delay in treatment of 1 week allowed micrometastases to develop. Treatment with octreotide significantly (P < 0.001) reduced the median hepatic replacement of liver by tumour compared with that of control rats given saline (controls: HSN 76.4 per cent, K12/Tr 17.5 per cent, WB2054M 43.9 per cent; octreotide treatment delayed 18 h: HSN 2.7 per cent, K12/Tr 0.6 per cent, WB2054M 1.3 per cent; octreotide treatment delayed 1 week: HSN 9.3 per cent, K12/Tr 2.5 per cent, WB2054M 2.3 per cent). These results clearly indicate that octreotide significantly inhibits the growth and development of experimental liver metastases. Further studies are required both to delineate the mechanism of action and to investigate these effects in a clinical setting.

Animals↗