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Biomedical subjects

D R Fletcher

Publications and source records attributed to D R Fletcher.

79 records · Page 5Linked to original sources
PubMedDate not supplied

Laparoscopic cholecystjejunostomy as palliation for obstructive jaundice in inoperable carcinoma of pancreas.

Malignant obstructive jaundice can be palliated by either surgical bypass, which has the advantage of long-term patency, or by stent placement, which has the advantage of initial lower morbidity and mortality. We describe a technique, laparoscopic cholecystjejunostomy, which has the advantage of both. We predict that laparoscopic surgery, which has already had a major impact on biliary stone surgery, will also have a major impact on interventional endoscopic retrograde cholangiopancreatography.

Cholecystostomy↗
PubMedDate not supplied

Preoperative assessment of pancreatic malignancy using endoscopic ultrasound.

BACKGROUND: Endoscopic ultrasound (EUS) has been regarded as the most accurate modality for locoregional staging of pancreatic malignancy. However, several recent studies have questioned this. The current study assessed the accuracy of EUS in determining preoperative resectability of pancreatic neoplasia. METHODS: A retrospective review was performed of patients with pancreatic malignancy who had preoperative EUS and underwent surgery. EUS-predicted resectability was compared with surgical resectability. Where available, accuracies of vascular and nodal staging were also assessed. RESULTS: Forty-five patients were identified (mean age 60 years, age range = 36-79 years). All patients underwent surgical exploration; vascular staging was available in 32 cases and 17 cases underwent surgical resection. The sensitivity, specificity, and accuracy of EUS in determining unresectability were 66%, 100%, and 78% respectively. Overall EUS stage concurred with surgical stage in 56%, greater than surgical stage in 4%, and less than surgical stage in 40%. Vascular staging on EUS had a sensitivity of 69% and a specificity of 100%. Accuracy of nodal staging was 71%. CONCLUSION: EUS had a high specificity for assessing unresectable pancreatic malignancy. This technique should be used to avoid unnecessary surgical exploration of incurable lesions. However, EUS had only a moderate sensitivity, and a proportion of patients staged preoperatively as having resectable disease will not be surgically resectable.

Carcinoma, Pancreatic Ductal↗
PubMedDate not supplied

The intrarenal site of calcitonin gene-related peptide degradation in the isolated perfused rat kidney.

1. Calcitonin gene-related peptide (CGRP) is a potent vaso-active 37 amino acid peptide, typically elevated in plasma from patients with medullary thyroid cancer (MTC), but undetectable in the plasma of normal subjects. 2. The kidney is a major site for the clearance of exogenously infused CGRP but the intrarenal site of this clearance is unknown. Extra-organ clearance is also significant for CGRP, and whereas the site and mechanism of this degradation remain uncertain, the vasculature has been postulated as the most likely site. 3. The isolated perfused rat kidney (IPRK) was studied to (i) localize the intrarenal site of CGRP clearance and (ii) determine the contribution of the renal vasculature to the clearance of CGRP. The half-life of CGRP in the filtering IPRK was 63.9 +/- 4.5 min, whereas blocking of filtration by elevation of the perfusate osmolarity abolished the degradation. This suggests that (i) renal CGRP degradation occurs after glomerular filtration with intratubular metabolism and (ii) that there is no active CGRP degradation in the (glomerular) capillary endothelium. 4. These results do not support the theory that renal vascular endothelium plays a major active role in CGRP degradation.

Animals↗
PubMedDate not supplied

Experimental mesenteric ischaemia in sheep: gut peptide release and haemodynamic changes.

Mesenteric ischaemia remains a frequently lethal condition. An improvement in survival is only likely with earlier diagnosis. Even with action upon early diagnosis and re-establishment of circulation, fatal shock often follows. This study was designed to determine the possible role of gastrointestinal regulatory peptides in the haemodynamic pathophysiology of acute mesenteric arterial ischaemia and whether measurement of these peptides would have diagnostic potential. Fourteen anaesthetized sheep were studied, seven with acute superior mesenteric artery (SMA) occlusion and seven with acute superior mesenteric and coeliac artery (SMA + CA) occlusion. Changes in peptide levels and haemodynamic changes were similar in the two experimental groups, but were more pronounced in the more severe ischaemia of SMA + CA occlusion. No major changes in systemic plasma gastrin, pancreatic polypeptide, neurotensin and vasoactive intestinal polypeptide (VIP) occurred during ischaemia. There was, however, a five-fold increase in VIP in portal venous plasma during SMA + CA occlusion. In the reperfusion period there were increases in VIP concentrations in both systemic and portal circulations in both groups. During ischaemia there was a rise in mean arterial pressure and peripheral resistance and a fall in cardiac output. Reperfusion was characterized by systemic and splanchnic vasodilation coincident with the rise in systemic plasma VIP. It is concluded that VIP which is released from the ischaemic intestine is likely to mediate a component of vasodilation seen during reperfusion.

Animals↗
PubMedDate not supplied

Biological potency of neurotensin metabolites in vivo: importance of alcohol 'fixation' of blood.

Neurotensin (NT), a 13-amino acid peptide, is released from the ileum following a meal. It is metabolized principally by the kidney and in the circulation to N-terminal fragments and apparently rapidly degraded C-terminal fragments. The present study was designed to compare the biological activity (plasma pancreatic polypeptide response) and the clearance kinetics of NT(1-13), the N-terminal fragment NT(1-11) and the C-terminal fragment NT(8-13). To measure accurately the circulating concentrations of short-lived NT fragments in the circulation, a method was devised of collecting blood directly into alcohol ('alcohol fixation'). The alcohol fixation procedure prevented the post-collection losses of the C-terminal fragment NT(8-13) and established that, based on blood levels achieved, NT(8-13) had 70% of the pancreatic polypeptide stimulating potency of NT(1-13). Nevertheless, the metabolic clearance rate of NT(8-13) was about sevenfold higher than the intact molecule, NT(1-13), suggesting that circulating C-terminal fragments have a minor physiological role. When the N-terminal fragment NT(1-11) was infused, there was no sustained effect on pancreatic polypeptide secretion although it was cleared at a rate similar to that of NT(1-13). It is concluded that the use of alcohol fixation prevents post-collection losses of NT fragments and enables true biological potencies of short-lived fragments to be assessed. The biological activity of NT resides in the C-terminus which, once split from the protective N-terminus, is rapidly degraded in the circulation. The remaining intact but inactive N-terminus is relatively stable.

Animals↗
PubMedDate not supplied

Peptic disease: can we afford current management?

BACKGROUND: While surgery has the potential to cure peptic disease (ulceration and reflux), the development in the 1970s of H2 receptor antagonists saw them replace surgery in the management of peptic symptoms, controlling disease while the medication was taken. Medical cure at least in the case of a duodenal ulcer is now also possible by the use of anti-Helicobacter therapy. METHODS: Australian Pharmaceutical Benefits Scheme (PBS) and Medicare data on the treatment of peptic disease were reviewed. RESULTS: The data showed that medical cure of duodenal ulcer is rarely attempted. While elective surgical treatment for duodenal ulcer, highly selective vagotomy, has decreased 10-fold in 10 years, prescriptions for antisecretory agents (H2 and proton pump) are doubling every 2 years (increasing from 6.7 to 7.8% of PBS budget). Meanwhile upper gastrointestinal endoscopy rates are doubling every 5 years. By comparison, the most appropriate treatment, anti-Helicobacter therapy, is prescribed at 1/50th the rate of antisecretory agents and over 2 years decreased to 1/80th. Antisecretory treatment has not been effective in reducing mortality from duodenal ulcer, at least not in New South Wales. CONCLUSIONS: If the principle of treatment is to decrease cost and prevent complications by curing duodenal ulcer, then current practice is a failure. A management algorithm for peptic symptoms which has the potential to relieve symptoms, cure ulcer when present, minimize surgery and reduce complications and cost is proposed for the purpose of debate.

Algorithms↗