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Biomedical subjects

H A Reber

Publications and source records attributed to H A Reber.

At least 145 records · Page 8Linked to original sources
PubMed1977

Pancreatic secretion in hamsters with pancreatic cancer.

Pancreatic secretory abnormalities develop in most persons with pancreatic cancer and have been attributed to ductal obstruction. These experiments investigated whether abnormal secretion results instead from carcinogen-induced changes in the secreting cells. Fifty male Syrian Golden hamsters (40 to 100 grams) received weekly injections of di-isopropyl-nitrosamine (250 mg/kg, subcutaneously), and survivors and age-matched controls were studied after 3.5 to 6.5 months of treatment. Pancreatic secretion was stimulated by secretin or cholecystokinin (2 units/kg, intravenously, as a bolus). After each stimulus four 15-minute collections of pancreatic juice were analyzed for HCO3- and Cl- or total protein, amylase, trypsin, and chymotrypsin. The organs were examined histologically. Pancreatic ductal adenocarcinoma developed in 30% of the animals at 5 months, 56% at 5.5 months, and 100% at 6.5 months. The animals without cancer either had hyperplasia of the duct epithelium or were histologically normal. The histologic appearance of acinar tissue and protein secretion were normal in all groups. The tumors did not obstruct the major ducts. In all treated animals the pancreatic secretory response to secretin was of low volume, low maximal [HCO3-] and HCO3- output, and low [Cl- + HCO3-]; these changes progressed with time. The secretory abnormalities antedated the appearance of the neoplasms and were not caused by obstruction.

Amylases↗
PubMed1976

The risk and accuracy of pancreatic biopsy.

Pancreatic biopsy in 171 patients produced complications in 4.7 per cent and death in 1.7 per cent. The biopsy diagnosis was confirmed in 86 per cent but was falsely negative in 14 per cent of pancreatic cancers. Frozen sections were interpreted correctly in all cases. Wedge biopsy resulted in fewer complications and fewer false-negative results than needle biopsy and is preferable except for periampullary lesions in which transduodenal needle biopsy is best. When the biopsy incision transected a pancreatic duct, suture ligation and drainage avoided complications. Open transduodenal biopsy of periampullary lesions was reliable, but the duodenotomy closure leaked in 10 per cent of the cases. Pancreatic biopsy with confirmation of malignancy should precede pancreaticoduodenectomy in most cases of suspected pancreatic cancer.

Adenocarcinoma↗
PubMed1976

Microcannulation--a new micropuncture technique application in cat pancreas secretion.

A new micropuncture technique of microcannulation has been developed and applied in cats to study exocrine secretion in the pancreatic ducts. Two micropipets of different diameters are assembled with the smaller pipet (10-20 mum) mounted inside the larger (25-50 mum). Using the combination, a larger pancreatic duct (less than 300 mum) is directly punctured and the inner pipet is advanced into the lumen of a small (20-50 mum) duct, which would otherwise be inaccessible. In anesthetized cats, during maximal stimulation with secretin (GIH 4-6 units/kg per h iv) the average chloride concentration of juice obtained from small ducts (25-50 mum) was 106 +/- 3 meq/1 and from large ducts (50-150 mum) was 75 +/- 5 meq/1. The results were confirmed by conventional micropuncture techniques which were technically more difficult. This method to collect fluid from small ducts is more physiological than direct micropuncture and thus the technique is a useful addition to micropuncture methodology.

Animals↗
PubMed1975

Surgical treatment of late postgastrectomy syndromes.

An analysis of the experience at the University of California Hospital, San Francisco, with the diagnosis and treatment of fifty-nine postgastrectomy syndromes shows that stomal obstruction (sixteen patients), the most common syndrome, was best treated by total reconstruction rather than stomal revision. Disappointment with the results of other procedures for the dumping syndrome (50 per cent improvement) has convinced us of the need to adopt the use of reversed jejunal interposition for surgical treatment of this condition. Because a precise etiologic diagnosis of bilious vomiting is often elusive, the preferred procedure is isoperistaltic jejunal interposition, since it eliminates the afferent loop and prevents bile from entering the stomach. All five patients with malabsorption were improved by conversion from BII to BI. Four of five patients with diarrhea were improved by various procedures (not including a reversed segment of intestine in the midjejunum). Three patients with reflux alkaline gastritis were improved by Roux-en-Y gastrojejunostomy or isoperistaltic jejunal interposition. Either is effective. Thus, in our experience if an unquestionable diagnosis of stomal obstruction, malabsorption, or reflux alkaline gastritis can be established, there is ample justification for an optimistic outlook regarding surgical therapy.

Adult↗
PubMedDate not supplied

The pathology of chronic pancreatitis.

We describe the current concepts of the pathology of alcoholic and obstructive chronic pancreatitis (CP). These 2 types of CP possess distinct pathological features. Alcoholic CP is associated with a lobular distribution of the lesions, with both obstruction (from protein plugs) and dilatation of the canalicular and intercalated ducts. In alcoholics, the concentration of protein in the pancreatic juice is increased, making the precipitation of proteinaceous plugs likely. Obstructive CP, on the other hand, is rarely associated with intraductal precipitates; the small ducts are often normal in appearance, but exocrine damage is much more widespread. The complications of CP are varied. Jaundice, while usually transient, may occasionally be permanent. This results from the compression of the distal common bile duct by fibrotic changes in the pancreatic head. Transient or permanent obstruction of the duodenum and/or colon may also occur. Nearby vessels may be involved, leading to thrombosis and/or hemorrhage from veins or arteries. Electron microscopic changes recently described in the pancreatic nerves may play a role in the etiopathogenesis of the severe pain so common in patients with CP.

Alcoholism↗
PubMedDate not supplied

Lymph node involvement as a prognostic factor in pancreatic cancer.

The finding of metastatic disease in lymph nodes predicts a poor outcome for patients with adenocarcinoma of the head of the pancreas. Nodal metastases occur in as many as one-half of the patients who currently undergo resection with small tumors (less than 2 cm in diameter). There is some evidence that a more extensive lymphatic and soft tissue resection than is commonly done could prolong survival. This possibility should be tested in a prospectively designed study.

Adenocarcinoma↗
PubMedDate not supplied

Polyethylene pancreatic duct stent-induced changes in the normal dog pancreas.

This study was undertaken to evaluate the frequency, severity, and reversibility of stent-induced pancreatic ductal and parenchymal changes in the normal dog pancreas. Six adult mongrel dogs underwent duodenotomy and placement of 5F polyethylene pancreatic duct stents into the main pancreatic duct. After 8 weeks of stenting, the animals were randomly assigned to one of three groups: group I (n = 2), sacrifice; group II (n = 2), stent removal followed by sacrifice after an 8-week recovery period; group III (n = 2), the stent was exchanged and kept in place for an additional 8 weeks. In group III at 16 weeks the stent was removed, and the animals were allowed to recover for 8 weeks before sacrifice. Pancreatograms were obtained at each operation and were normal before stent placement. Gross and histologic evaluation was performed at the time of sacrifice. All stented animals developed radiographic, gross, and histologic abnormalities. Pancreatograms showed duct dilation in the stented region associated with a short stenosis at the mid to upstream segment of the stent. Group III animals had more advanced radiographic changes than group I and II animals. The radiographic findings were associated with gross evidence of fibrosis, which increased proportionately with the length of the stenting period. Group III animals developed moderate to severe pancreas atrophy. Histologic changes of obstructive pancreatitis were present in most experimental dogs. The results of this study suggest that pancreatic stenting may cause permanent damage in the normal dog pancreas. The cause of the damage appears to be related to stent occlusion, perhaps exacerbated by local stent-induced trauma.

Animals↗
PubMedDate not supplied

Interleukin-10 protects against lethality of intra-abdominal infection and sepsis.

The aim of this study was to determine whether interleukin-10 would alter locally derived and systemic proinflammatory cytokine expression and protect from the lethality of cecal ligation and puncture. Three groups of Sprague-Dawley rats were used. Group 1 underwent cecal manipulation. Groups 2 and 3 underwent cecal ligation and puncture. Group 2 received intraperitoneal saline injections beginning 1 hour after cecal ligation and puncture and every 3 hours thereafter for 24 hours. Group 3 received intraperitoneal interleukin-10 one hour after cecal ligation and puncture and every 3 hours thereafter. Animals were killed at 6 and 24 hours after cecal ligation and puncture or sham operation. Serum tumor necrosis factor-alpha (TNF-alpha) levels were determined by enzyme-linked immunosorbent assay. TNF-alpha messenger RNA expression was determined by reverse transcriptase-polymerase chain reaction using Beta-actin as the internal standard. There was a twofold increase (P <0.001) in TNF-alpha mRNA in the liver at 6 and 24 hours after cecal ligation and puncture when compared to rats treated with interleukin-10. There was a twofold increase (P <0.05) in TNF-alpha mRNA in the lung observed only at 24 hours after cecal ligation and puncture when compared to rats treated with interleukin-10. Serum levels of TNF-alpha were elevated at 6 hours in control animals, and this effect was abolished by the administration of interleukin-10. There was no difference in mortality rates at 6 hours (0% for all groups); however, at 24 hours 57% (4/7) mortality was observed in group 2 vs. 0% (0/20) in groups 1 and 3. Interleukin-10 given after the onset of cecal ligation and puncture protects against the lethality of intra-abdominal sepsis.

Abdominal Abscess↗
PubMedDate not supplied

Angiogenesis inhibitor TNP-470 reduces human pancreatic cancer growth.

In this study we investigated the effects of the angiogenesis inhibitor TNP-470 on human pancreatic cancer cells in vitro and in vivo. The action of TNP-470 on vascular endothelial growth factor (VEGF) was also assessed. In vitro human pancreatic cancer cells (MIAPaCa-2, AsPC-1, and Capan-1), and human umbilical vein endothelial cells (HUVEC) were exposed to increasing concentrations (1 pg/ml to 100 microg/ml) of TNP-470. Cell proliferation was assessed after 3 days by cell count and MTT assay. In vivo, 5 x 10(6) pancreatic cancer cells were injected subcutaneously into nude mice. Four weeks later, 1 mm3 fragments of the resulting tumors were implanted into the pancreas of other mice. Animals received either TNP-470 (30 mg/kg every other day) or vehicle subcutaneously for 14 weeks. The volume of the primary tumor and metastatic spread were determined at autopsy. Concentrations of VEGF were determined in serum (VEGF(S)) and ascites (VEGF(A)) by enzyme-linked immunosorbent assay. Microvessel density was analyzed by immunohistochemistry in CD31-stained tumor sections. In vitro, proliferation and viability of the human pancreatic cancer cell lines were significantly inhibited at high concentrations of TNP-470 (> 1 microg/ml). In contrast, TNP-470 effectively decreased the growth of HUVEC at 100 pg/ml. In vivo, tumor volume and dissemination scores were significantly lower in all three pancreatic cancer cell lines. VEGF(S) and VEGF(A) were not different between treated groups. Treatment with TNP-470 significantly reduced neoangiogenesis in tumors of all three human pancreatic cancer cell lines: MIAPaCa-2 = 74.8 +/- 7.8/0.74 mm2 vs. 24.8 +/- 3.7/0.74 mm2; AsPC-1 = 65.3 +/- 5.0/0.74 mm2 vs. 26.0 +/- 3.4/0.74 mm2; and Capan-1 = 82.2 +/- 5.8/0.74 mm2 vs. 26.9 +/- 2.5/0.74 mm2 (P < 0.001). However, survival was not statistically different between groups. TNP-470 reduced tumor growth and metastatic spread of pancreatic cancer in vivo. This was probably due to the antiproliferative effect of the agent on endothelial cells rather than to the direct inhibition of pancreatic cancer cell growth. TNP-470 activity was not associated with alteration of VEGF secretion.

Adenocarcinoma↗
PubMedDate not supplied

Therapy for pancreatic cancer with a recombinant humanized anti-HER2 antibody (herceptin).

The HER2/neu oncogene is overexpressed in human pancreatic cancer, but the clinical significance of that overexpression is uncertain. In the present study we investigated the antitumor efficacy of Herceptin, a new recombinant humanized anti-HER2/neu antibody, which exhibits cytostatic activity on breast and prostate cancer cells that overexpress the HER2 oncogene. That antibody may retard tumor growth in certain patients with those diseases. We quantified HER2 expression in various human pancreatic cancer cell lines and studied the bioactivity of this antibody both in vitro and in vivo. Growth inhibition by Herceptin was observed in vitro in cell lines with high levels of HER2/neu expression. Cell lines with low levels of this protein did not respond significantly to the antibody. In vivo we studied two different pancreatic cancer cell lines in an orthotopic mouse model of the disease. Herceptin treatment suppressed tumor growth in the MIA PaCa-2 tumor cell line, which expressed high levels of HER2/neu. These data suggest that Herceptin treatment of patients with pancreatic cancer who express high levels of the HER2/neu oncogene may be reasonable.

Adenocarcinoma↗
PubMedDate not supplied

Interleukin-10 reduces circulating levels of serum cytokines in experimental pancreatitis.

Over the past few years, evidence has accumulated that implicates proinflammatory cytokines as the mediators responsible for the escalation of acute pancreatitis into a multisystem disease. It has been shown that the degree of serum cytokine elevation, particularly the macrophage-derived cytokines interleukin-1, interleukin-6, and tumor necrosis factor-alpha, correlates with the severity and outcome of acute pancreatitis. Interleukin-10 is an anti-inflammatory cytokine that inhibits cytokine production from the macrophage. The aim of this study was to determine whether interleukin-10 would decrease both the severity of acute pancreatitis and the level of circulating proinflammatory cytokines. Ninety female mice were divided into three equal groups. Group 1 (controls) received intraperitoneal saline solution. Groups 2 and 3 received intraperitoneal cerulein (50 mg/kg/hr) for 7 hours. In addition, group 3 was given 1500 units of intraperitoneal interleukin-10, beginning 1 hour after the induction of acute pancreatitis and every 3 hours thereafter. Animals were killed at 3-hour intervals. Blood samples were obtained for serum amylase and cytokine determinations (interleukin-1beta, interleukin-6, and tumor necrosis factor-alpha). Pancreata were dissected free and fixed in formalin for blinded histologic scoring. Interleukin-10 reduced the serum levels of interleukin-1beta, interleukin-6, tumor necrosis factor-alpha, and amylase in comparison to untreated animals with pancreatitis (P < 0.05). Pancreatic edema, necrosis, and inflammatory cell infiltrate were also reduced in those animals given interleukin-10 (P <0.05). Histologic score, serum cytokines, and amylase levels are elevated during acute pancreatitis. Interleukin-10 given therapeutically, that is, after the onset of acute pancreatitis, lessened the severity of disease, probably through inhibition of the macrophage. This was associated with a decrease in circulating cytokine levels.

Animals↗