Pancreatic blood flow and its role in the pathophysiology of pancreatitis.
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Acute Disease↗
Biomedical subjects
M P Lewis
Publications and source records attributed to M P Lewis.
Randomised trial of laparoscopic exploration of common bile duct versus postoperative endoscopic retrograde cholangiography for common bile duct stones.
BACKGROUND: The management of stones in the common bile duct in the laparoscopic era is controversial. The three major options are preoperative endoscopic retrograde cholangiography (ERCP), laparoscopic exploration of the common bile duct (LECBD), or postoperative ERCP. METHODS: Between August, 1995, and August, 1997, 471 laparoscopic cholecystectomies were done in our department. In 427 (91%), satisfactory peroperative cholangiography was obtained. In 80 (17%) of these cases there were stones in the common bile duct, 40 patients were randomised to LECBD and 40 to postoperative ERCP. If LECBD failed, patients had either open exploration of the common bile duct or postoperative ERCP. If one postoperative ERCP failed, the procedure was repeated until the common bile duct was cleared of stones or an endoprosthesis was placed to prevent stone impaction. The primary endpoints were duct-clearance rates, morbidity, operating time, and hospital stay. Analyses were by intention to treat. FINDINGS: Age and sex distribution of patients was similar in the randomised groups. Duct clearance after the first intervention was 75% in both groups. By the end of treatment, duct clearance was 100% in the laparoscopic group compared with 93% in the ERCP group. Duration of treatment was a median of 90 min (range 25-310) in the laparoscopic group (including ERCPs for failed LECBD) compared with 105 min (range 60-255) in the postoperative ERCP group (p = 0.1, 95% CI for difference -5 to 40). Hospital stay was a median of 1 day (range 1-26) in the laparoscopic group compared with 3.5 days (range 1-11) in the ERCP group (p = 0.0001, 95% CI 1-2). INTERPRETATION: LECBD is as effective as ERCP in clearing the common bile duct of stones. There is a non-significant trend to shorter time in the operating theatre and a significantly shorter hospital stay in patients treated by LECBD.
Cholangiopancreatography, Endoscopic Retrograde↗
Expression of an embryonic fibronectin splicing variant in human masseter muscle.
Fibronectin is an extracellular matrix protein that is a key constituent of all skeletal muscles. Its deposition increases in a number of pathological conditions, including some muscular dystrophies in which a progressive increase in lower-face height is often noted. It has been shown in other organ systems that increased deposition of fibronectin is associated with changes in the expression of differentially spliced isoforms of the molecule. This investigation documents the expression of mRNA coding for fibronectin and its splicing variants, EIIIA and EIIIB, in biopsies of masseter muscle from normal and long-face patients, using reverse transcriptase-polymerase chain reaction. Expression was compared with that occurring in anatomically and embryologically differing somatic skeletal muscle. Masseter expressed fibronectin mRNA containing the EIIIA but not the EIIIB splicing variant. Conversely, somatic skeletal muscle expressed neither the EIIIA nor EIIIB variants. There were no differences between expression of fibronectin containing the EIIIA splicing variants in masseter from normal and long faces. These results suggest that variations in fibronectin expression reflect the differing functional demands of muscles from different anatomical locations and indicate that jaw and somatic muscle belong to different allotypes.
Base Sequence↗
Intragastric alcohol causes endothelin release from feline pancreas.
The mechanism by which alcohol causes pancreatic damage is still largely unknown. One important contributory factor may be the endothelins, potent vasoconstricting endothelial-derived peptides. The aim of this study was to examine in vivo endothelin release from the pancreatic vascular endothelium after alcohol ingestion. In anesthetized cats immunoreactive endothelin was measured in serum after instillation of alcohol into the stomach (20 ml, 40%). After intragastric alcohol, a rise in endothelin was seen in pancreatic venous effluent (to a mean of 24.5 +/- 7.7 pg/ml at 60 min). Control serum from the femoral artery exhibited no rise in endothelin (2.11 +/- 1.2 pg/ml). Pancreatic blood flow was significantly decreased in a further group to 93% basal after intravenous infusion of 0.1 nmol/kg ET-1 and to 61% after infusion of 1 nmol/kg ET-1. Portal serum levels of endothelin were 105 pg/ml and 15 pg/ml, respectively, immediately following bolus infusion and decreased to normal levels within 120 sec. We conclude that the serum endothelin rise after intragastric ethanol may be a major factor behind the drop in pancreatic blood flow.
Animals↗
Ethanol-mediated neutrophil extravasation in feline pancreas.
Ethanol is a common cause of both acute and chronic pancreatitis. Studies in other organs suggest that polymorphonuclear neutrophils activated by ethanol may cause tissue injury in a variety of conditions. The aim of this study was to investigate the effects of ethanol on neutrophil extravasation in the feline pancreas. Pancreata were isolated and perfused at different flow rates with varying concentrations of ethanol in either a physiological or neutrophil depleted perfusate. Neutrophil extravasation was assessed by measuring pancreatic tissue myeloperoxidase (MPO) activity. Ethanol at 2.5% (54.25 mmol/liter) was the lowest concentration that still caused significant neutrophil extravasation (3.1+/-0.8 vs 1.9+/-0.2 units, P<0.05) and was accompanied by an increase in vascular resistance of 15%. Reduction of pancreatic perfusion by 15% did not significantly increase neutrophil extravasation. (1.1+/-0.3 vs 1.6+/-0.2 units, NS) Perfusion of the pancreas with neutrophil-depleted blood containing either ethanol or saline, followed by perfusion with an ethanol-free perfusate, showed an increase in neutrophil extravasation in the ethanol group compared to the control group (3.2+/-0.9 vs 1.9+/-0.2 units, P<0.05). In conclusion, ethanol causes neutrophil extravasation in the feline pancreas independent of blood flow changes and occurs despite the absence of direct neutrophil exposure to ethanol.
Animals↗
Stenting does not decompress the pancreatic duct as effectively as surgery in experimental chronic pancreatitis.
BACKGROUND: In humans with chronic pancreatitis (CP), pancreatic interstitial pressure (IP) is elevated and pancreatic blood flow (PBF) is reduced. The efficacy of surgical decompression (SD) of the pancreatic duct (ie, pancreaticojejunostomy) is believed to be due to its ability to decrease IP and pancreatic vascular resistance (Rp), which increases PBF. Pancreatic duct stenting (STE) also probably reduces IP and Rp, which may explain its efficacy. The purpose of this study was to compare the efficacy of SD with STE. METHODS: CP in cats was created by narrowing the main pancreatic duct. Six weeks later, CP and normal pancreata were isolated and perfused ex vivo under basal conditions and after secretin stimulation. In normal and CP glands, IP and perfusion pressure were measured and Rp (U) was calculated. In two additional groups, the pancreatic duct was decompressed, either by stenting or by complete transection of the duct with a longitudinal capsulotomy. RESULTS: In CP glands, IP and Rp were increased and secretory output was markedly reduced compared with the normal (0.65 +/- 0.30 mm Hg and 0.46 +/- 0.04 U vs 3.90 +/- 0.80 mm Hg and 1.68 +/- 0.05 U; P < .05). Secretin administration (2 units) increased IP and Rp in CP glands (6.60 +/- 1.10 mm Hg and 2.87 +/- 0.07 U; P < .05), but these values did not chang in normal glands (0.81 +/- 0.20 and 0.53 +/- 0.03 U; NS). STE and SD decreased IP and Rp in CP glands (2.20 +/- 0.20 to 1.0 +/- 0.40 mm Hg and 1.20 +/- 0.015 to 0.90 +/- 0.01 U, respectively; P < .05). Both methods prevented an increase of IP and Rp after secretin administration. IP and Rp decreased to a greater degree following SD, compared with STE (P < .05). CONCLUSIONS: Both STE and SD decreased IP and Rp in this experimental model of CP. However, SD was significantly more effective than STE.
Animals↗
Interleukin-10 reduces the systemic inflammatory response in a murine model of intestinal ischemia/reperfusion.
BACKGROUND: Intestinal ischemia/reperfusion (I/R) is known to increase systemic cytokine levels, as well as to activate neutrophils in distant organs. This study was designed to investigate the effect of interleukin-10 (IL-10) on cytokine release, pulmonary neutrophil accumulation, and histologic changes in a murine model of I/R. METHODS: Forty female Swiss-Webster mice were divided into four groups. Group 1 underwent 45 minutes of superior mesenteric artery occlusion followed by 3-hour reperfusion (I/R). Group 2 underwent laparotomy alone (Sham). Group 3 underwent I/R, but was treated with IL-10, 10,000 units IP every 2 hours, starting 1 hour before reperfusion (Pretreatment). Group 4 was treated with an equal dose of IL-10, starting 1 hour after reperfusion (Posttreatment). All animals were killed at 3 hours, standard assays were performed for serum cytokine levels, and lung myeloperoxidase activity and intestinal histology were scored. RESULTS: Serum cytokines (TNF-alpha and IL-6), lung myeloperoxidase levels, and histologic score were significantly reduced when IL-10 was administered either before or after reperfusion. CONCLUSIONS: IL-10 reduced the severity of local and systemic inflammation in a murine model of intestinal I/R when given before or after reperfusion injury. These observations suggest that IL-10 may exert its effect by blocking cytokine production and distant organ neutrophil accumulation.
Animals↗
An ETa/ETb endothelin antagonist ameliorates systemic inflammation in a murine model of acute hemorrhagic pancreatitis.
BACKGROUND: Endothelin peptides are polykines with strong vasoconstrictor properties. We have previously shown that endothelin antagonism (PD145065) reduces the local severity of acute pancreatitis. We now investigated the effect of endothelin antagonism on systemic inflammation in a model of acute hemorrhagic pancreatitis. METHODS: Forty-two mice were divided into four groups. Group 1 was fed standard food plus PD145065 every 8 hours. Group 2 was fed a choline-deficient ethionine (CDE) supplemented diet and given saline every 8 hours. Group 3 was fed a CDE diet and treated with PD145065 every 8 hours from initiation of diet. Group 4 was fed a CDE diet and given PD145065 from 48 hours after initiation of diet. Animals were killed at 70 hours. Serum was collected. Pancreata and lung tissue were harvested. RESULTS: Histology score, serum amylase level, lung myeloperoxidase, and interleukin (IL)-10 were all significantly reduced in both treatment groups (groups 3 and 4) (p < 0.05). IL-6 levels were reduced in group 3 only (p < 0.05). The mortality rate did not differ among any of the groups. CONCLUSIONS: Endothelin antagonism decreased the severity of acute pancreatitis and reduced markers of systemic inflammation. Late treatment at 48 hours failed to prevent the rise in IL-6. Mortality rates were unaffected by treatment.
Acute Disease↗
Management decisions for unusual periampullary tumors.
The pessimism associated with the treatment of pancreatic cancer may result in inappropriate management in certain patients thought to have that disease. We analyzed the recent UCLA experience with a variety of periampullary tumors in which various issues concerning management were unusual. The records of nine patients (age 15-75 years) with pancreatic or periampullary tumors were reviewed retrospectively. The tumor was evident on CT scan in all patients. The diameter of the mass was greater than 5 cm in five cases. Eight of the tumors appeared to arise from the pancreas, but at exploration, two were found to originate from other structures (duodenum and retroperitoneum). One patient with an apparent gastric lesion on CT scan was found to have a mass of pancreatic origin at operation. Operative procedures included: pancreaticoduodenectomy (four), distal pancreatectomy (three), total pancreatectomy (one), and retroperitoneal tumor resection (one). Pathological diagnoses included: solid and papillary epithelial neoplasm (two), mucinous cystic neoplasm (two), serous microcystic adenoma (two), myositis ossificans (one), degenerative neurilemoma (one), spindle cell tumor (one), and intraductal papillary carcinoma (one). We conclude that patients with large or unusual-appearing pancreatic or periampullary tumors should be managed aggressively. Major resections can be done safely with the achievement of an excellent quality of life in individuals at the extremes of age. Unlike the usual pancreatic ductal adenocarcinoma, the prognosis for many of these neoplasms is excellent.
Adenocarcinoma↗
Pexicrine effects of basement membrane components on paracrine signaling by renal tubular cells.
Paracrine interactions between tubular epithelium and interstitial cells have been assumed to be mediated largely by soluble cytokines. While the role of extracellular matrix (ECM) and matrix metalloproteinases (MMPs) in modifying cell function is widely appreciated, the role of the renal tubular basement membrane in modulation of tubulointerstitial function has not been studied. To establish whether those components of the ECM which support tubular epithelial cells also influence cell function (that is, a pexicrine effect), we studied their effects on paracrine signaling between epithelium and fibroblasts. Primary cultures of rat renal proximal tubular epithelial cells (PTE) were cultured on laminin (LN), collagen types-IV and -I (COL-IV, COL-I) and fibronectin (FN). PTE attained confluence more rapidly when grown on LN = COL-IV > COL-I = FN = plastic. On all substrates PTE produced the MMPS, gelatinase-A and -B and collagenase with an apparent increase in gelatinase-A and -B production when cultured on LN. MMPs were found to be secreted both apically and basally with basal secretion predominating, except on LN where secretion was primarily from the apical surface. Cultures of rat renal cortical interstitial fibroblasts were established and characterized. Cortical fibroblasts (CF) were found to secrete gelatinase-A and collagenase. Conditioned medium (CM) from PTE cultured on COL-IV stimulated proliferation of CF but proliferation was unaltered by CM from PTE grown on other substrates. By contrast, co-culture of PTE on LN with CF suppressed collagenase and gelatinase activity in both cell types, indicating a bi-directional, paracrine modulation of MMP production. Thus in the tubulointerstitium, the BM components LN and COL-IV not only fulfill a structural role but act as signaling molecules with differential effects which modify the function of the tubular epithelium and its paracrine interaction with adjacent fibroblasts. The initiation of interstitial fibrosis induced by injury to the tubular basement membrane may reside in the perturbation of this interaction.
Animals↗
Human endometrial fibroblasts immortalized by simian virus 40 large T antigen differentiate in response to a decidualization stimulus.
Human endometrial fibroblasts have been immortalized by infection with simian virus 40 large T antigen and established as a permanent cell line, St-2. Biochemical differentiation of this cell line has been demonstrated by the ability of a decidualizing stimulus, 8-bromo-cAMP plus medroxyprogesterone acetate (MPA), to induce PRL secretion and increase the enzymatic activity of estrone sulfatase. MPA, alone or in combination with estradiol, was unable to elicit this response, but potentiated the effect of 8-bromo-cAMP on PRL production and estrone sulfatase activity. The increase in PRL protein was accompanied by an increase in PRL messenger RNA and increased expression of the insulin-like growth factor-binding protein-1 messenger RNA. The St-2 cell PRL transcript was larger than the pituitary PRL transcript, suggesting its initiation from the distal, nonpituitary, PRL promoter. This was confirmed by reverse transcription-PCR analysis of PRL transcripts using primers specific for the additional sequences present only in the 5'-untranslated region of RNA initiated from the distal promoter. Transient transfection of a reporter construct containing 3000 bp of DNA 5' to the decidual-specific promoter of the human PRL gene demonstrated that cAMP was capable of activating this distal promoter in St-2 cells. In conclusion, this novel cell line provides an interesting new model in which to pursue aspects of biochemical differentiation of human endometrium in vitro.
8-Bromo Cyclic Adenosine Monophosphate↗
Matrix metalloproteinases (MMPs) in renal fibrosis.
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Animals↗
Ischaemia-reperfusion mechanisms in acute pancreatitis.
The role of ischaemia in the pathogenesis of acute pancreatitis is unknown. Some experimental studies have shown that ischaemia has little effect on the pancreas, while others have found an association with pancreatic injury. Ischaemia-reperfusion damage has been well documented in other sites such as the intestine, cardiac muscle, and skeletal muscle. However, in the pancreas, injury is usually seen only after complete ischaemia, which is uncommon clinically. Experimental chronic pancreatitis is characterized by low pancreatic blood flow, low interstitial pH, and impaired pancreatic tissue oxygenation, which are all findings consistent with the ischaemia-reperfusion mechanisms. Acute pancreatitis is also associated with a reduction in pancreatic blood flow and evidence of free radical generation, similarly suggesting the possibility of ischaemia-reperfusion injury. Ethanol ingestion, which is commonly associated clinically with both chronic and acute pancreatitis, may itself contribute to an ischaemic-reperfusion injury. We have shown that administration of ethanol to cats decreases pancreatic blood flow and may also directly activate neutrophils. Further investigation is needed to determine whether or not these findings are also associated with an ischaemia-reperfusion injury.
Acute Disease↗
Value of laparotomy in the diagnosis of obscure gastrointestinal haemorrhage.
Over a nine year period a total of 137 patients were investigated for obscure gastrointestinal bleeding on one surgical unit. In 20 patients visceral angiography strongly suggested the presence of caecal or right colonic angiodysplasia. These patients were treated by an appropriate colectomy and they are not considered further in this study. Similarly lesions of the small bowel detected by preoperative investigations are not considered here. Fifty five patients were offered diagnostic laparotomy after the failure of other investigations to establish a diagnosis. Two patients refused. A diagnostic laparotomy was performed in the remaining 53. At operation if no visible lesion was seen an on table enteroscopy was performed using a colonoscope passed per oram and, if necessary, per anum. In nine (17%) patients no cause for bleeding was found. In 18 (34%) patients there was a small bowel vascular anomaly, in 14 (26%) a small bowel tumour, in four (7.5%) a bleeding Meckel's diverticulum, and in eight (15%) other miscellaneous lesions. Laparotomy, with on table enteroscopy where indicated, elucidated the cause of bleeding in 44 patients (83%). It was associated, however, with a postoperative death rate of 7.5% (four patients). After seemingly appropriate surgery, rebleeding occurred in 14 patients (26%). Of 18 patients with small bowel vascular anomalies seven rebled (39%), at an average follow up interval of 32 months.
Aged↗
The Medicare fair hearing process.
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Insurance Claim Reporting↗
Localization and surgical management of insulinoma.
Over a 14-year period 34 patients were referred for surgical treatment of insulinoma. The diagnosis was confirmed by demonstrating hypoglycaemia with inappropriate hyperinsulinaemia during prolonged fasting. Selective visceral angiography localized 30 solitary benign insulinomas and two carcinomas. In two patients with islet cell hyperplasia, angiography demonstrated a single lesion only. Ultrasonography had a sensitivity of 15 per cent and computed tomography a sensitivity of 24 per cent in the localization of tumours. All patients but one were treated by operation. Eighteen tumours were enucleated and 13 (including both patients with islet cell hyperplasia) were treated by distal pancreatectomy. Two patients underwent negative primary exploration; both had single adenomas removed at re-exploration. There were no operative deaths but nine patients (predominantly those undergoing pancreatic resection) had complications. Thirty-one patients were symptom-free following operation at a mean follow-up of 16 months.
Adolescent↗
Regulation by interleukin-1 beta of growth and collagenase production by choriocarcinoma cells.
Impaired trophoblastic invasion and proliferation have been implicated in the pathogenesis of eclampsia, pre-eclampsia, spontaneous abortions and intra-uterine growth retardation (IUGR). First trimester trophoblast cells (which do not grow in culture) and choriocarcinoma (BeWo) (which grow spontaneously, and are used as a model for proliferating trophoblast) were incubated with interleukin-1 beta (IL-1 beta). BeWo cell growth was decreased dose-dependently by exogenous IL-1 beta at concentrations of 100-1000 pg/ml. This effect was first detected after 24 h of incubation with IL-1 beta, and persisted for up to 96 h of culture. In contrast, trophoblast cells isolated from first trimester placental tissue showed no growth response when stimulated with IL-1 beta. The levels of active interstitial collagenase produced by BeWo cells were increased by IL-1 beta (100-1000 pg/ml), which paralleled the decrease in cell growth. First trimester trophoblast cells produced lower levels of collagenase and this was not affected by incubation of the cells by IL-1 beta. These results indicate that IL-1 beta may regulate placental development, but further development of culture systems for first trimester trophoblast will be needed before this result can be confirmed.
Cell Division↗
Hereditary calcific pancreatitis in an English family.
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Adolescent↗