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Biomedical subjects

H A Reber

Publications and source records attributed to H A Reber.

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

Kupffer cell blockade reduces hepatic and systemic cytokine levels and lung injury in hemorrhagic pancreatitis in rats.

Severe acute pancreatitis (AP) is associated with both the local (pancreatic) release of cytokines and an elevation in their systemic plasma concentrations. This may lead to organ dysfunction and death of the patient. The aims of this study were to investigate the source(s) of systemic cytokine production during experimental AP. Forty-two rats were allocated to five groups (control, sham operation and saline injection, sham operation and gadolinium chloride injection, intraductal sodium-taurocholate infusion and saline injection, or intraductal sodium-taurocholate infusion and gadolinium chloride injection). Blood from the iliac artery, portal vein, and hepatic vein, along with tissue from the pancreas, liver, and lung, were collected. Serum levels of TNFalpha, IL-1beta, IL-6, and IL-10 were determined by enzyme-linked immunosorbent assay. Tissue mRNA for IL-1beta and IL-10 was assessed by reverse-transcription polymerase chain reaction. In untreated animals with AP, the lowest serum cytokine levels were found in the portal vein. In the hepatic vein, the levels of TNFalpha, IL-1beta, and IL-6 were higher. The highest serum levels were detected in the systemic circulation. In the gadolinium chloride-treated group, there was no increase in hepatic or systemic cytokine levels and less lung injury was observed. Extrapancreatic cytokine production from both the liver and the lung contributed significantly to systemic levels of TNFalpha, IL-1beta, IL-6, and IL-10 in this experimental model of AP.

Acute Disease↗
PubMed1999

How accurate is helical computed tomography for clinical staging of pancreatic cancer?

BACKGROUND: Our goal was to determine if findings on an index computed tomography (CT) scan would correlate with survival in patients with pancreatic adenocarcinoma. We know that as this tumor extends out of the gland, survival decreases. Are there any CT findings that assess tumor extension sufficiently that also correlate with survival? Once identified, these CT areas would be the best factors to clinically stage patients. METHODS: Between 1993 and 1997, 160 patients with biopsy-proven adenocarcinoma of the pancreatic head were included if an index helical CT scan and clinical follow-up were available. All CT scans were reviewed by the same radiologist blinded for outcomes. CT scans were interpreted using a graded extension of tumor out of the pancreatic head in four areas: retroperitoneum (RP); anterior pancreatic capsule (S); portal/superior mesenteric veins (PV); and celiac/superior mesenteric arteries (A). Extension of tumor was graded as follows: Grade 0 (negative margin); 1 (suspicious); 2 (positive); or 3 (extensively involved). Also recorded and graded were signs of metastases: nodal enlargement > or =1.5 cm (N); and lesions consistent with hepatic metastases (H). Survival was compared between grades for each CT area using the methods of Kaplan and Meier and relative risk estimates of death (Cox regression models). RESULTS: Compared with grade 0, the following CT areas had significantly decreased survival curves: grade 1 (only S and A), grade 2 and 3 (RP, PV, S, A). N and H did not correlate with survival unless > or =1.5 cm nodes were in the liver or splenic hilum or there were multiple liver nodules. CONCLUSION: Although postoperative microscopic H or N involvement is a reliable prognostic sign, only extensive CT involvement of H or N predicts survival preoperatively. A better CT finding that predicts decreased survival preoperatively was extension out of the pancreatic head (especially S or A). Clinical methods of staging should use CT areas such as S, A, PV, and RP, and not H and N.

Adenocarcinoma↗
PubMed1999

Surgical approach in patients with acute pancreatitis. Is infected or sterile necrosis an indication--in whom should this be done, when, and why?

The morbidity and mortality rates of severe acute pancreatitis are related to the degree of pancreatic necrosis that accompanies the attack and to the presence of infection. The decision about whether and when to operate on these patients is often difficult, and it requires mature clinical judgment. Proven infection of pancreatic necrosis is an absolute indication for surgical intervention, at which time surgical doffebridement and drainage should be performed. Most patients with sterile necrosis eventually respond to conservative nonsurgical medical management. In patients who remain critically ill for weeks or whose clinical course deteriorates despite maximal intensive care, surgery may be appropriate. Even when these guidelines are followed, the mortality (15% to 40%) and morbidity (approximately 80%) rates remain high.

Debridement↗
PubMed1999

Feline model of chronic obstructive pancreatitis: effects of acute pancreatic duct decompression on blood flow and interstitial pH.

BACKGROUND: The mechanism by which duct decompression (DD) relieves pain in patients with chronic pancreatitis (CP) is unknown. CP is associated with increased tissue pressure (IP), low pancreatic microvascular blood flow (PMBF), and interstitial pH (pH(I)). The aims of this study were to examine the effects of acute DD on PMBF, increased IP, and pH(I) in cats with CP. METHODS: The main pancreatic duct was partially obstructed. At 6 weeks PMBF (ml/min/100g H2 gas clearance), IP (mmHg needle electrode), and pH(I) (microelectrode) were measured before and after secretin stimulation. The duct was then opened, and the studies were repeated. RESULTS: PMBF normally increased with secretin stimulation (118 +/- 20 versus 271 +/- 52, P < 0.05). IP was unaltered, and pH(I) decreased as hydrogen ions produced during bicarbonate secretion were dissipated (7.41 +/- 0.01 versus 7.38 +/- 0.01, P < 0.05). In CP, basal PMBF was lower than normal (51 +/- 6 versus 118 +/- 20, P < 0.05) and decreased with stimulation (51 +/- 3.5 versus 31 +/- 3.5, P < 0.05). Basal pancreatic IP was increased (3.47 +/- 0.7 versus 0.05 +/- 0.3, P < 0.05) and increased further with secretory stimulation (3.47 +/- 0.7 versus 4.41 +/- 0.7, P < 0.05) (a compartment syndrome). The low basal pancreatic pH(I) (7.23 +/- 0.02) did not change with secretin stimulation, since bicarbonate secretion was minimal. DD decreased IP (3.66 +/- 0.5 versus 2.81 +/- 0.5, P < 0.05) and increased PMBF (50 +/- 6 versus 79 +/- 6, P < 0.05) and pH(I) (7.24 +/- 0.02 versus 7.34 +/- 0.02, P < 0.05). The normal increase in PMBF after stimulation was restored (79 +/- 6 versus 218 +/- 54, P < 0.05). pH(I) now increased with stimulation (7.34 +/- 0.002 versus 7.37 +/- 0.002, P < 0.05), perhaps due to the marked hyperaemic response. CONCLUSIONS: DD acutely restored basal and stimulated PMBF and IP towards normal. Basal pancreatic pH(I) also improved and reflects the underlying ischaemia.

Animals↗
PubMed1999

Effect of pancreaticojejunostomy on fibrosis, pancreatic blood flow, and interstitial pH in chronic pancreatitis: a feline model.

OBJECTIVE: To study the relation between fibrosis, pancreatic blood flow (PMBF), interstitial pH (pHi), and the effects of pancreaticojejunostomy (PJ) in chronic pancreatitis. BACKGROUND: Chronic pancreatitis is associated with low PMBF and pHi, suggesting the existence of underlying ischemia. METHODS: In cats, the main pancreatic duct was partially obstructed and the animals were studied 2, 4, 6, and 8 weeks later. PJ was performed after 2 and 4 weeks of ductal obstruction and studied 4 weeks later. PMBF and pH were measured before and after stimulation with secretin and cholecystokinin. pHi was measured with microelectrodes, PMBF by hydrogen gas clearance. Histologic analysis of the pancreas with Sirius red (collagen stain) and fast green FCF (noncollagen protein) stains allowed semiquantitative analysis of the ratio between collagen and total protein (C/TP). RESULTS: With the evolution of chronic pancreatitis, there is a progressive increase in the collagen content and C/TP ratio, a reduction in basal PMBF and pHi, and loss of the normal response to stimulation. Early PJ restores collagen content, C/TP ratio, and basal and stimulated PMBF and pHi to normal. PJ performed in established CP returns the C/TP ratio to normal, improves basal PMBF, and restores the normal hyperemic response to secretion. Basal pHi is improved and the "acid tide" associated with secretin returns, but there is still no response to cholecystokinin. CONCLUSIONS: Pancreaticojejunostomy restores the elevated collagen and C/TP ratio to normal and reverses the ischemia present in CP. The authors speculate that restoration of PMBF and its normal response to stimulation allows "regeneration" and restoration of secretory function.

Animals↗
PubMed1999

Acute pancreatitis.

Efforts to unravel the intracellular processes that occur in acute pancreatitis continue. In cerulein pancreatitis, new evidence supports the idea that a very early event is premature trypsinogen activation triggered by lysosomal cathepsin B. Clinicians persist in trying to identify more sensitive and specific prognostic signs of the severity of attacks of pancreatitis; one study suggests that computer-based neural networks may be an alternative to biochemical markers and clinical scoring systems. The systemic severity of episodes of pancreatitis seems to be related to a multitude of proinflammatory cytokines and chemokines acting at sites distant from the pancreas. Selective blockade of some of these peptides (eg, endothelin-1 and platelet-activating factor) has decreased mortality and distant organ damage in animal models and may deserve clinical evaluation. Gene therapy may be more efficient than pharmacologic therapy in increasing anti-inflammatory cytokine (interleukin-10) levels. Clinical studies have further underlined the usefulness of prophylactic antibiotics in severe acute pancreatitis. Radiologic and endoscopic techniques may be alternatives to surgery for certain complications of pancreatitis (eg, infected necrosis and pseudocysts) in particular subsets of patients.

Journal Article↗
PubMed1998

Mechanism of increased lung injury after acute pancreatitis in IL-10 knockout mice.

BACKGROUND: IL-10 is a potent anti-inflammatory cytokine which inhibits inflammatory cytokine release from all tissue sites. Hepatic cytokine release from Kupffer cells (KC) is one important source of inflammatory cytokines and may be the main one causing lung damage in acute pancreatitis (AP). Here we studied the KC contribution to lung injury in IL-10 knockout (KO) mice, in which tissue inflammatory cytokine release from all sites is unrestrained, and AP is more severe. METHODS: Three- to 4-week-old C57BL/6J mice and KO mice on a C57BL/6J background were used. Control mice received regular chow and gadolinium chloride (GD; 1 mg/100 g iv), to inhibit KC activity, or saline. Pancreatitis mice received a choline-deficient, ethionine-supplemented diet for 66 h to induce AP and saline or GD injections iv. After 66 h, lung tissue was assessed for edema, myeloperoxidase (MPO), and superoxide dismutase (SOD). Histology was scored in a blinded fashion. RESULTS: In pancreatitis KO mice, KC blockade had no effect on the degree of lung edema, lung neutrophil infiltration, and lung histology score. As expected, each of these parameters was more severe in the KO mice than in the normal mice: lung wet/dry ratio 5.3 +/- 0.2 versus 4.3 +/- 0.13; lung MPO (U/g) 1.9 +/- 0.2 versus 1.1 +/- 0.08; histology score 7.1 +/- 0.8 versus 5.3 +/- 0.5. CONCLUSION: Endogenous IL-10 is important in reducing the lung injury in this model of AP. KC-derived cytokines were of minor importance, compared to those derived from all other tissue sites.

Acute Disease↗
PubMed1998

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↗
PubMed1998

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↗
PubMed1998

Small peripancreatic veins: improved assessment in pancreatic cancer patients using thin-section pancreatic phase helical CT.

OBJECTIVE: Recent studies have shown evaluation of the small peripancreatic veins to have potential in improving pancreatic cancer staging. This study was performed to determine the effectiveness of thin-section pancreatic phase helical CT images in visualizing these veins. MATERIALS AND METHODS: Seventy-two patients (30 with pancreatic adenocarcinoma and 42 with no pancreatic disease) underwent dual-phase helical CT with thin-section pancreatic phase acquisition (40-70 sec after i.v. contrast initiation at 3 ml/sec) and hepatic phase acquisition (70-100 sec). Visualization (with diameter measurement) or nonvisualization of the posterior superior pancreaticoduodenal vein (PSPDV), anterior superior pancreaticoduodenal vein (ASPDV), and gastrocolic trunk was recorded for both acquisitions. We also correlated surgical tumor resectability with the status of the small peripancreatic veins. RESULTS: Visualization of peripancreatic veins was significantly better on pancreatic phase images than on hepatic phase images for both healthy individuals (PSPDV, 88% of the veins visualized on the pancreatic phase images versus 50% on the hepatic phase images; ASPDV, 93% on the pancreatic phase images versus 48% on the hepatic phase images; gastrocolic trunk, 98% on the pancreatic phase images versus 76% on the hepatic phase images) and for pancreatic cancer patients (PSPDV, 97% on the pancreatic phase images versus 57% on the hepatic phase images; ASPDV, 77% on the pancreatic phase images versus 43% on the hepatic phase images) (p < .05). The exception was the gastrocolic trunk in cancer patients (83% on the pancreatic phase images versus 77% on the hepatic phase images) (p > .05). In pancreatic cancer patients, 11 dilated peripancreatic veins were identified on the pancreatic phase images compared with six on the hepatic phase images. However, only one of the 11 dilated peripancreatic veins was in a patient with surgically resectable disease. CONCLUSION: In a dual-phase helical CT protocol, thin-section pancreatic phase images provided visualization of the small peripancreatic veins that was superior to hepatic phase images, providing further support for the use of this protocol in pancreatic cancer evaluation.

Adenocarcinoma↗
PubMed1998

Endoscopic measurement of pancreatic blood flow.

A reduction of pancreatic blood flow has been observed in acute and chronic pancreatitis in animal models. Most available blood flow techniques are either too invasive or impractical to carry out in humans. Since the arrival of endoscopic retrograde cholangiopancreatography (ERCP), our understanding and management of pancreatic disorders has gradually improved. It may now be utilized to investigate what is believed to be a very important factor in the pathogenesis of pancreatic disease and symptoms: pancreatic tissue perfusion.

Acute Disease↗
PubMed1998

Radical pancreatectomy.

In an effort to cure more patients, the standard pancreaticoduodenectomy (Whipple procedure) has been modified to include a wider soft tissue and lymph node dissection, and a resection of a segment of the superior mesenteric and portal veins. The operation is described, and the results are critically reviewed. Although the procedure can be performed safely, and with little additional morbidity compared to a standard resection, there is no objective evidence that it increases the cure rate.

Humans↗
PubMed1998

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↗
PubMed1997

Interleukin-10 prevents early cytokine release in severe intraabdominal infection and sepsis.

Early release of macrophage-derived proinflammatory cytokines, such as tumor necrosis factor (TNF), interleukin (IL)-1, and IL-6, are important in the pathogenesis of septic shock and multisystem organ failure in various models of sepsis. IL-10 is a mediator that inhibits cytokine release from activated macrophages. The aim of this study was to determine if IL-10 would decrease serum cytokine elevation in a murine model of cecal ligation and puncture (CLP). CLP in animals is a model that closely mimics the physiologic changes seen in human sepsis. Four groups of 14 female Swiss-Webster mice were used. Group 1 underwent laparotomy alone, groups 2, 3, and 4 underwent laparotomy and CLP. Groups 1 and 2 received intraperitoneal (IP) saline injections to serve as control vehicle. Group 3 (prophylactic) received 10,000 U IP IL-10 1 hr prior to CLP and every 3 hr thereafter. Group 4 (therapeutic) received 10,000 U IP IL-10 1 hr following CLP and every 3 hr thereafter. Animals were sacrificed at 3 and 9 hr following CLP. Serum TNF-alpha, IL-1 beta, and IL-6 were determined by enzyme-linked immunosorbent assay (ELISA), CLP produced a significant rise in serum TNF,IL-6, and IL-1 in untreated controls. Prophylactic or therapeutic administration of IL-10 significantly attenuated this early rise in serum cytokines. These results support the hypothesis that (1) CLP produces an early systemic rise in macrophage-derived cytokines and (2) IL-10 given either before or after the onset of CLP-induced intraabdominal infection and sepsis is able to inhibit this early release of macrophage-derived systemic mediators. IL-10 has potential clinical benefits in the therapeutic management of intraabdominal infection and sepsis.

Abdomen, Acute↗
PubMed1997

Diagnostic workup of patients with suspected pancreatic carcinoma: the University of California-Los Angeles approach.

BACKGROUND: A large number of diagnostic procedures (e.g., ultrasound, computed tomography [CT] scan, fine-needle aspiration [FNA], angiography, endoscopic retrograde cholangiopancreatography [ERCP], and laparoscopy), are available to the clinician as he/she pursues the workup of patients who are thought to have a pancreatic (periampullary) malignancy. Not all of these procedures should be used in every patient and some have been overused. METHODS: Based on a current literature review and their own experience, the authors describe the rationale of the diagnostic workup in patients with suspected pancreatic carcinoma in a single institution (a university medical center). RESULTS: Helical CT scan provides the best overall assessment of patients with periampullary malignancies, and it is often the only test required. If the patient's history and blood test abnormalities suggest pancreatic carcinoma and the helical CT scan shows a mass in the head of the pancreas that appears to be resectable, the patient should be prepared for surgery. If no mass is apparent on the helical CT scan, a diagnostic ERCP is indicated. If microscopic proof of the diagnosis will avoid surgery, then an FNA for cytology should be performed. When unresectability appears likely and cannot be confirmed in less invasive ways, laparoscopy is indicated. CONCLUSIONS: In patients with periampullary malignancies, helical CT scan provides the best overall assessment. Guidelines are presented for the selective use of ultrasound, FNA, ERCP, and laparoscopy, which are important for the most cost-effective workup of these patients.

Angiography↗
PubMed1997

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↗