Search PubMed⌕ Search

Biomedical subjects

H A Reber

Publications and source records attributed to H A Reber.

At least 55 records · Page 3Linked to original sources
PubMed1997

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↗
PubMed1997

Interleukin 10 reduces the severity of acute pancreatitis in rats.

BACKGROUND & AIMS: Previous studies have documented the effectiveness of interleukin (IL)-10 if given before the onset of experimental acute pancreatitis. This study examined whether IL-10, a cytokine that inhibits macrophage release of inflammatory mediators, would alter the severity of acute pancreatitis if given before or after the induction of disease. METHODS: Eighty-four Sprague-Dawley rats were divided into four groups. Group 1 received intravenous saline, and groups 2, 3, and 4 received intravenous cerulein (8.5 microg x kg(-1) x h(-1)). Group 3 was also given 150,000 U of intraperitoneal IL-10 1 hour before cerulein infusion and every 3 hours thereafter. Group 4 received 150,000 U intraperitoneal IL-10 2 hours after cerulein infusion and every 3 hours thereafter. Serum amylase and tumor necrosis factor (TNF)-alpha levels were measured before and 3, 9, or 15 hours after induction of pancreatitis. Animals were killed at these time points. Pancreata were analyzed for edema and TNF-alpha mRNA and TNF-alpha protein concentrations and were graded histologically. RESULTS: Serum amylase, TNF-alpha mRNA, and TNF-alpha protein levels, pancreatic edema, and histological score were significantly reduced when IL-10 was administered either before or after induction of pancreatitis. Serum TNF-alpha levels were undetectable. CONCLUSIONS: IL-10 attenuated the severity of experimental acute pancreatitis if given either before or after the induction of the disease. These results are consistent with the hypothesis that the macrophage is important in determining the severity of acute pancreatitis in this model.

Acute Disease↗
PubMed1997

Effect of ethanol on pancreatic interstitial pH and blood flow in cats with chronic pancreatitis.

OBJECTIVE: The objective of this study was to investigate the effects of ethanol on pancreatic blood flow and interstitial pH in chronic pancreatitis. BACKGROUND: Ethanol is known to contribute to the development of both acute and chronic pancreatitis. However, it is unclear how ethanol precipitates episodes of acute pancreatic inflammation in the setting of chronic pancreatitis. In a model of chronic pancreatitis in cats, it is known that pancreatic blood flow is abnormally low and decreases further after ethanol ingestion. Because it is possible that this reduction in blood flow might be damaging to the pancreas, we investigated the effects of ethanol on pancreatic interstitial pH, an index of pancreatic ischemia. METHODS: In normal cats and cats with obstructive chronic pancreatitis, pancreatic blood flow and interstitial pH were measured using the hydrogen gas clearance technique and pH microelectrode, respectively. RESULTS: In normal cats, intragastric, but not intravenous, ethanol reduced both pancreatic blood flow by 62% (p < 0.05) and interstitial pH (7.38 +/- 0.03 to 7.20 +/- 0.03, p < 0.05). In cats with chronic pancreatitis in which basal pancreatic blood flow was already only 60% of normal flow, both intragastric and intravenous ethanol decreased both pancreatic blood flow (intragastric, 40% decrease, p < 0.05; intravenous, 34% decrease, p < 0.05) and interstitial pH (intragastric, 7.24 +/- 0.04 to 7.08 +/- 0.04, p < 0.05; intravenous 7.20 +/- 0.08 to 7.07 +/- 0.07, p < 0.05). CONCLUSIONS: This profound decrease in pH, lasting up to 2 hours after ethanol exposure in the chronic pancreatitis animals, suggests the possibility of ischemic cellular damage to the pancreas. These findings may explain the pathogenesis of bouts of acute pancreatic inflammation after ethanol ingestion in the setting of chronic disease.

Animals↗
PubMed1997

Local staging of pancreatic cancer: criteria for unresectability of major vessels as revealed by pancreatic-phase, thin-section helical CT.

OBJECTIVE: This study was conducted to determine the criteria for unresectability of major peripancreatic vessels in patients with pancreatic carcinoma as revealed by optimally enhanced, pancreatic-phase thin-section helical CT. SUBJECTS AND METHODS: Twenty-five patients with pancreatic adenocarcinoma who underwent local dissection during curative or palliative surgery also underwent preoperative pancreatic-phase thin-section helical CT (40- to 70-sec delay, 2.5- to 3-mm collimation). Tumor involvement of the portal and superior mesenteric veins and the celiac, hepatic, and superior mesenteric arteries was prospectively graded on a 0-4 scale based on circumferential contiguity of tumor to vessel. Subsequent surgical results were then correlated with the CT grades. RESULTS: At surgery, definitive evaluation was possible for 80 vessels. Forty-eight of 48 vessels graded 0 and three of three vessels graded 1 were resectable. Four of seven vessels graded 2, seven of eight vessels graded 3, and 14 of 14 vessels graded 4 were unresectable. A threshold of between grades 2 and 3, which corresponded to tumor involvement of one-half circumference of the vessel, yielded the lowest number of false-negatives and an acceptable number of false-positives for unresectability. Such a threshold would have yielded a sensitivity of 84%, a specificity of 98%, a positive predictive value of 95%, and a negative predictive value of 93% for unresectability of the vessels studied. CONCLUSION: A grading system for tumor involvement of the major vessels in patients with pancreatic adenocarcinoma can be based on the degree of circumferential contiguity of tumor to vessel. Involvement of vessel to tumor that exceeds one-half circumference of the vessel is highly specific for unresectable tumor.

Adenocarcinoma↗
PubMed1997

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↗
PubMed1996

Palliation for pancreatic cancer. Feasibility of laparoscopic cholecystojejunostomy and gastrojejunostomy in a porcine model.

BACKGROUND: Although laparoscopy reveals undetected metastases in many patients with pancreatic cancer, most surgeons have chosen to proceed directly with laparotomy in an attempt at resection or for palliation of biliary and gastric outlet obstruction. In an effort to overcome this limitation, this study attempted to determine the feasibility of laparoscopic cholecystojejunostomy and gastrojejunostomy. METHODS: Under general anesthesia, seven pigs underwent laparoscopic cholecystojejunostomy and gastrojejunostomy using either a hand-sutured or the stapled/sutured technique. RESULTS: Mean operating time was less with the stapled/sutured vs hand-sutured technique (150 +/- 21 vs 230 +/- 13 min, P < 0.05). All animals recovered completely and there was no change in their weight or liver function tests as a result of the procedure. At sacrifice, all anastomoses were patent, although some were significantly narrowed in these unobstructed animals. CONCLUSIONS: These results suggest that simultaneous laparoscopic palliation of biliary and gastric outlet obstruction is feasible. We believe these results warrant further study in the clinical setting.

Anastomosis, Surgical↗
PubMed1996

Interleukin-10 prevents death in lethal necrotizing pancreatitis in mice.

BACKGROUND: Cytokines derived from macrophages may play an integral role in the evolution of acute pancreatitis. Interleukin-10 (IL-10), a potent antiinflammatory cytokine, prevents the activation of macrophages and their release of inflammatory cytokines. The aim of this study was to determine whether treatment with IL-10 decreased the severity of experimental acute pancreatitis. METHODS: Thirty female Swiss Webster mice were divided into three groups. Acute pancreatitis was induced by using a choline-deficient, 0.5% ethionine supplemented (CDE) diet. Group A (controls) received CDE diet alone. Group B was pretreated with 10,000 units of intraperitoneal IL-10 at the onset of feeding and every 8 hours thereafter. Group C received IL-10 33 hours after beginning the CDE diet and every 8 hours thereafter. One half of the animals in each group was killed at 54 hours; the remaining living animals were killed at 80 hours. Serum amylase levels (units per liter) were determined at 54 and 80 hours. Pancreata were harvested and fixed in formalin. Histologic characteristics were graded on a scale from 0 to 4 (normal to most abnormal) in a blinded fashion by two investigators. RESULTS: Serum amylase level and histologic score (edema, inflammation, hemorrhage, and necrosis) were significantly reduced when IL-10 was administered either prophylactically or therapeutically (p < 0.01). At 54 hours all animals were alive. Mortality was reduced at 80 hours in both groups treated with IL-10 compared with those fed the CDE diet alone (p < 0.001). CONCLUSIONS: These results suggested that macrophages play an integral role in determining the severity of acute pancreatitis in this animal model. The finding that IL-10 decreased inflammation and prevented death, even when given after acute pancreatitis was established, suggests that it may have potential for clinical use.

Amylases↗
PubMed1996

Two-phase helical CT for pancreatic tumors: pancreatic versus hepatic phase enhancement of tumor, pancreas, and vascular structures.

PURPOSE: To quantitatively evaluate and validate a two-phase helical computed tomographic (CT) protocol for evaluation of pancreatic tumors. MATERIALS AND METHODS: Twenty-seven patients with pathologically proved pancreatic adenocarcinomas prospectively underwent two-phase CT examination with helical acquisition during the pancreatic phase (40-70 seconds after infusion of intravenous contrast material at 3 mL/sec) and the hepatic phase (70-100 seconds after infusion). Mean CT attenuation values of tumor, bordering pancreas, and all major peripancreatic vessels were obtained for both time intervals. RESULTS: Mean tumor-pancreas contrast was significantly greater during the pancreatic phase (67 HU +/- 19) than the hepatic phase (39 HU +/- 16) (P < .001) This was the result of both greater enhancement of normal pancreas and lower tumor enhancement during the pancreatic phase. Opacification of all vascular structures, including the portal vein, was also greater during the pancreatic phase (P < .001). CONCLUSION: Two-phase helical CT with pancreatic phase acquisition provides statistically significantly better pancreatic, arterial, and portal venous enhancement than that of hepatic phase imaging, with improved tumor-pancreas contrast.

Adenocarcinoma↗
PubMed1996

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↗
PubMed1995

Pylorus-preserving Whipple resection for pancreatic cancer. Is it any better?

OBJECTIVE: To compare the short- and long-term morbidity and mortality rates of the standard Whipple pancreatoduodenectomy (SW) and its pylorus-preserving modification (PPW) in patients with malignant periampullary disease. DESIGN: Retrospective medical record review and quality of life assessment by telephone interview. SETTING: University medical center. STUDY PARTICIPANTS: Sixty-seven patients who underwent pancreatoduodenectomy (52 SW and 15 PPW) from June 1988 to January 1994. INTERVENTION: The SW and PPW. MAIN OUTCOME MEASURES: Operative features and short- and long-term complications were analyzed with respect to the type and stage of cancer and the kind of pancreatic resection. Mean follow-up was 32 months (range, 1 to 5 years). RESULTS: The operative mortality rate for all patients who had a pancreatic resection was 1.5%. The diagnoses in the PPW vs SW groups were pancreatic cancer (four vs 27 patients), ampullary cancer (six vs seven patients), duodenal cancer (zero vs six patients), and bile duct cancer (five vs one patient). Operative mortality rates (0% vs 1.55%) and operative times (2 minutes longer for SW) were similar. Delayed gastric emptying (61% vs 41%) was more common in the PPW group, resulting in a longer hospitalization (24 vs 18 days) and a greater cost in the PPW group (P = .04). In the PPW group, a mean of five lymph nodes was removed compared with 10 in the SW group (P = .04). CONCLUSIONS: The data provided no evidence of any advantage for the PPW in patients with malignant periampullary tumors. We continue to advocate the SW for pancreatic cancer.

Adult↗
PubMed1995

Role of nitric oxide in the relationship of pancreatic blood flow and exocrine secretion in cats.

BACKGROUND/AIMS: Recent studies have suggested that, in the gastrointestinal tract, nitric oxide is an important mediator of alterations in blood flow and, in some organs, a second messenger involved in secretion. This study examined the role of NO in changes in pancreatic blood flow associated with basal and stimulated pancreatic exocrine secretion. METHODS: In anesthetized cats, we determined the effects of the NO synthase inhibitor NG-monomethyl-L-arginine (10 mg/kg) and the NO donor sodium nitroprusside (10 micrograms.kg-1.min-1) on pancreatic secretion and blood flow (hydrogen gas clearance). RESULTS: NG-monomethyl-L-arginine had no effect on the increase in blood flow associated with secretin stimulation (271 +/- 52 vs. 290 +/- 50 mL.min-1.100 g-1) but reduced that associated with cholecystokinin stimulation (189 +/- 17 vs. 53 +/- 15 mL.min-1.100 g-1; P < 0.001). In contrast, NG-monomethyl-L-arginine significantly reduced both secretin- and cholecystokinin-stimulated secretion. Sodium nitroprusside had no effect on basal blood flow but significantly increased secretion. CONCLUSIONS: NO has a selective role in mediating changes in pancreatic perfusion and secretion. It seems to be important in stimulus-secretion coupling with both secretin and cholecystokinin but is only responsible for the accompanying increase in pancreatic blood flow with cholecystokinin.

Amino Acid Oxidoreductases↗
PubMed1995

Pancreatic interstitial pH in human and feline chronic pancreatitis.

BACKGROUND & AIMS: Advanced chronic pancreatitis is associated with a reduction in pancreatic blood flow. To determine the physiological significance of this decrease, pancreatic interstitial pH was measured in a model of obstructive chronic pancreatitis in cats and in patients with chronic pancreatitis. METHODS: In cats, pancreatic interstitial pH and blood flow were measured serially under basal conditions and after secretory stimulation as chronic pancreatitis evolved. Basal pancreatic interstitial pH was also measured in patients undergoing an operation for chronic pancreatitis or periampullary cancer (controls). RESULTS: In normal cats, pancreatic interstitial pH was 7.41 +/- 0.01 and blood flow was 124 mL.min-1.(100 g pancreas-1). With the evolution of chronic pancreatitis, interstitial pH and blood flow progressively decreased to 7.21 +/- 0.04 (P < 0.007) and 75 +/- 11 (P < 0.007), respectively. From 1 to 2 weeks, secretory stimulation reduced pancreatic interstitial pH and blood flow further, but as secretory function was lost, this effect disappeared. In patients with chronic pancreatitis, the interstitial pH was lower (7.02 +/- 0.06) than in controls (7.25 +/- 0.04; P < 0.05). CONCLUSIONS: These observations are consistent with the hypothesis that, in chronic pancreatitis, acidic metabolites associated with pancreatic secretion accumulate within the pancreas, probably because of impaired blood flow.

Adult↗
PubMed1995

Curative treatment for pancreatic neoplasms. Radical resection.

The available data suggest that lymph node involvement is an important prognostic factor in patients with carcinoma of the head of the pancreas. Lymph node metastases occur in as many as 50% of the cases of even the smallest pancreatic cancers now being diagnosed and resected (i.e., those < 2 cm in diameter). There is some evidence, especially from clinical experience in Japan, that wider lymphatic dissections (i.e., wider than those commonly done with the standard Whipple resection) may prolong survival. Unfortunately, many of the available data around the world are retrospective and are not randomized between the standard and the radical operation. Moreover, the pathologic material has not been staged uniformly according to accepted criteria. Thus the various series are not comparable. Comparisons between series require standardization with respect to stage of disease, pathologic classification, and treatment protocols. Before any modification of the standard pancreaticoduodenectomy is adopted, an appropriately designed study should be performed to test its efficacy. This study would also require a more comprehensive analysis of the pathologic material than is commonly performed today in the United States and Europe.

Humans↗
PubMed1995

Pancreatic vascular regulation in chronic pancreatitis in cats.

In experimental obstructive chronic pancreatitis the normal hyperaemic response to secretory stimulation is lost, suggesting abnormal vascular regulation. Vascular regulatory mechanisms were investigated by observing the effect of increments in portal pressure on pancreatic blood flow in normal cats and cats with chronic pancreatitis. Normal cats maintained pancreatic blood flow until portal pressure was > 15 mm Hg, after which it decreased. Total vascular resistance decreased until the portal pressure was 15 mm Hg and increased thereafter. These observations suggested that metabolic regulatory mechanisms prevailed while portal pressure was in the physiological range but myogenic mechanisms became dominant during portal hypertension. In chronic pancreatitis the basal pancreatic blood flow was reduced and was inversely proportional to portal pressure. Total vascular resistance increased as portal pressure increased. In chronic pancreatitis myogenic regulatory responses prevailed at all levels of portal pressure. In conclusion, intrinsic regulation of pancreatic blood flow was abnormal in cats with chronic pancreatitis. The loss of the predominance of metabolic regulation over the normal range of portal pressure may partly explain the reduction of pancreatic blood flow in response to secretory stimulation.

Animals↗
PubMed1994

Histologic changes after stenting of the pancreatic duct.

The placement of stents has been proposed as a possible modality to treat pancreatic diseases. Ductal changes observed on endoscopic retrograde cholangiopancreatography during stenting are believed to be reversible when the stents are removed. We describe a patient with normal anatomy on baseline pancreatograms who underwent endoscopic sphincterotomy, followed by stent placement for 9 months. Symptoms progressed, leading to a pancreaticoduodenectomy. Histologic evaluation of the head of the pancreas revealed more extensive inflammatory changes in the duct and parenchyma drained by the stent. This suggests that stent-induced changes noted on pancreatography correspond to parenchymal changes that may be severe and irreversible.

Cholangiopancreatography, Endoscopic Retrograde↗
PubMed1994

Compartment syndrome in experimental chronic obstructive pancreatitis: effect of decompressing the main pancreatic duct.

Chronic pancreatitis is characterized by persistent and severe pain, which can be relieved by decompression of the main pancreatic duct (MPD). Both ductal and interstitial pressures have been shown to be increased in chronic pancreatitis in patients. A study was carried out of pancreatic interstitial pressure and pancreatic blood flow in normal cats and those in which chronic obstructive pancreatitis had been induced 5 weeks earlier to determine the effect of decompression of the MPD. In the normal pancreas, median(interquartile range (i.q.r.)) basal interstitial pressure was 0.05(1.2) mmHg and median(i.q.r.) basal pancreatic blood flow 58.3(24.3) ml per min per 100 g. Secretory stimulation did not change the interstitial pressure significantly, but was associated with a 40 per cent increase in median(i.q.r.) blood flow to 81.8(45.8) ml per min per 100 g. In contrast, in chronic obstructive pancreatitis, the median(i.q.r.) basal interstitial pressure was 2.0(1.5) mmHg, which was significantly higher than in the normal gland, and median(i.q.r.) pancreatic blood flow was 38.3(9.8) ml per min per 100 g, significantly lower than in the normal pancreas. Furthermore, secretory stimulation was associated with a significant increase in median(i.q.r.) interstitial pressure to 3.3(1.6) mmHg and a simultaneous decrease in median(i.q.r.) blood flow to 31.5(13.7) ml per min per 100 g. After decompression of the MPD in cats with chronic obstructive pancreatitis, the median(i.q.r.) basal interstitial pressure was 2.0(1.4) mmHg and on secretory stimulation 1.8(1.5) mmHg. Decompression thus prevented the increase in interstitial pressure seen in the animals with obstruction. In contrast, ductal decompression improved the median(i.q.r.) basal pancreatic blood flow to 45.9(38.4) ml per min per 100 g and, furthermore, this increased significantly on secretory stimulation to a median(i.q.r.) of 81.4(47.8) ml per min per 100 g. Decompression thus restored the normal pattern of secretory hyperaemia. Within the confines of this model, these observations demonstrate that chronic obstructive pancreatitis exhibits a compartment syndrome that is relieved by duct drainage.

Animals↗
PubMed1994

Antimicrobial treatment of pancreatic infection in cats.

An investigation examined the efficacy of antibiotics in a novel feline model of pancreatic infection in acute pancreatitis. Acute pancreatitis was induced in cats using an established technique. In control animals (no pancreatitis) and cats with pancreatitis, Escherichia coli (10(4) in 0.1 ml) was placed in the pancreatic duct. Reoperation was performed after 24 h in six controls and six cats with pancreatitis. E. coli was cultured from the pancreas in five control animals and five cats with pancreatitis. Reoperation was performed after 1 week in ten controls, in 11 cats with pancreatitis and in nine with pancreatitis that were treated with cefotaxime (50 mg/kg intramuscularly three times daily) started 12 h after the induction of pancreatitis and administration of E. coli. Pancreatic infection developed in eight cats with pancreatitis compared with none of the cefotaxime-treated animals and none of the controls (P < 0.05). Cefotaxime reached bactericidal levels in pancreatic tissue and juice. In conclusion, ductal administration of E. coli caused pancreatic infection only in cats with acute pancreatitis. Early administration of an appropriate antibiotic was effective in treating pancreatic infection in acute pancreatitis.

Acute Disease↗