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Biomedical subjects

P J Blind

Publications and source records attributed to P J Blind.

At least 19 recordsLinked to original sources

Treatment of non-resectable pancreatic cancer with intraperitoneal 5-FU and leucovorin IV.

AIM: To explore the feasibility of intraperitoneal (IP) 5-fluorouracil (5-FU) and (IV) leucovorin for patients with advanced pancreatic carcinoma. MATERIALS AND METHOD: Thirty patients (11 men), median age 65 (range 36-74 years), with a non-resectable pancreatic carcinoma in stage III (n=2) and IV (n=28) were treated with IP 5-FU 750-1000 mg/m(2)and leucovorin IV 100 mg/m(2)for 2 days every 3rd week. Tumour effect was analysed with repeated computed tomography (CT) scans, performance status was estimated with Karnofsky's index (KI) and morphine consumption, and toxicity assessed using World Health Organization (WHO) criteria. RESULTS: Median survival time was 7 months (range 0-21). There was no difference in survival between patients with different grading, staging or tumour size. Regional and systemic toxicity: The treatment was well tolerated, with no grade III or IV complications or side-effects. The median KI showed a minor reduction during treatment. The median morphine consumption per 24 hours increased from 0 mg (range 0-250) at inclusion, to 70 mg (range 0-540) at exclusion. The median nadir (WBC) was 7.2x10(3)/mm(3)(range 5.2-18.8). All patients had abdominal discomfort and distension during IP installation. CONCLUSION: Intraperitoneal administration of 5-FU is feasible for patients with nonresectable pancreatic carcinoma. The treatment can induce a temporary stabilization of tumour growth and eventually prolong survival without adverse effects.

Adult↗

The influence of zymosan and indomethacin on liver and kidney tumor growth. An experimental study in rats.

Zymosan, a non-specific macrophage-stimulating agent, modifies favourably tumour growth in the liver but has minor effect on renal tumours. The mechanism accounting for variation is still to be clarified. The effect of zymosan on liver cancer may be mediated by the macrophage-monocyte system. Kupffer cells are in vitro cytotoxic against colon cancer cell lines. The kidney is sparse in macrophage elements. The prostaglandin synthesis inhibitor, indomethacin, inhibits tumor growth. In Wistar-FU rats inoculated in the liver and the kidney with an adenocarcinoma cell suspension, pretreatment with zymosan (3 mg x 100 g[-1]) significantly reduced both tumour take and liver volume. This effect was attenuated by concomitant administration of indomethacin (0.2 mg x 100 g[-1]). After 2 weeks there was still reduced liver tumour volume. No significant effects on tumour take or growth were observed when the cells were inoculated into the kidney. There was no significant effect of zymosan on an hepatoma in Lister-Hooded rats. Pretreatment with indomethacin had no effect on tumor take or initial growth.

Adenocarcinoma↗

Carboxylic ester hydrolase and amylase in ischemic pancreatitis in the guinea pig.

The observation that an elevated level of pancreatic carboxylic ester hydrolase (CEH) in serum is a more sensitive and specific marker of acute pancreatitis than is elevated serum amylase activity prompted us to explore whether these findings could be confirmed in an experimental model and, if so, to find the explanation behind this difference. We therefore developed a model for ischemic pancreatitis in the guinea pig and a sandwich enzyme-linked immunosorbent assay for determination of CEH in this species. There was a strong correlation between duration of ischemia and severity of pancreatic inflammation and between severity of inflammation and serum CEH level. In contrast, serum amylase was elevated only in animals with the most severe grade of inflammation. Amylase was, however, increased in urine in animals with mild inflammation, but the level did not increase with severity of inflammation. Only one of 31 animals had detectable CEH in urine. In animals with intermediate serum CEH levels the serum and biliary concentrations correlated, indicating that CEH may be cleared by the liver. Amylase was detectable in bile only in animals with high serum levels. The results confirm our observations made in previous clinical studies. A likely explanation for differences in serum levels of CEH and amylase is clearance from the circulation at different rates and, at least partly, via different routes, e.g., the liver and kidney, respectively.

Amylases↗

Diagnosis of traumatic pancreatic duct rupture by on-table endoscopic retrograde pancreatography.

We report on two children who sustained blunt abdominal trauma with pancreatic duct rupture diagnosed by ERP (endoscopic retrograde pancreatography). Examinations were done with patients on the operating table anesthetized for laparotomy (on-table ERP). In both patients, duct laceration remained undiagnosed by computerized tomography and ultrasonography. Operative strategy depends on whether the pancreatic duct is lacerated or not. Findings during on-table ERP allow decisions on operative strategy in patients with pancreatic trauma.

Adolescent↗

The value of routine biochemical tests in discriminating between malignant and benign pancreatic tumours.

The probability that routine hematological laboratory tests of liver and pancreatic function can discriminate between malignant and benign pancreatic tumours, incidentally detected during operation, was investigated. The records of 53 patients with a verified diagnosis of pancreatic carcinoma and 19 patients with chronic pancreatitis were reviewed with regard to preoperative total bilirubin, direct reacting bilirubin, alkaline phosphatase, glutamyltranspeptidase, aminotransferases, lactic dehydrogenase and amylase. Multivariate and discriminant analysis were performed to calculate the predictive value for cancer, using SYSTAT statistical package in a Macintosh II computer. Total and direct reacting bilirubin and glutamyltranspeptidase were significantly higher in patients with pancreatic carcinoma. However, only considerably increased levels of direct reating bilirubin were predictive of pancreatic carcinoma.

Adult↗

Carboxylic ester hydrolase. A sensitive serum marker and indicator of severity of acute pancreatitis.

When using clinical criteria, both falsely positive and falsely negative diagnoses of acute pancreatitis (AP) are often made. Based on a clinical study, elevated serum levels of the pancreatic lipolytic enzyme carboxylic ester hydrolase (CEH) was recently suggested to be a highly specific marker of acute pancreatitis. To determine the sensitivity of the test for AP, a study on patients with the diagnosis set objectively was necessary. In the present study, AP was diagnosed by contrast-enhanced computed tomography in 64 patients, and histopathological examination of tissue removed at laparotomy in 18 of them. By these criteria, 42 patients suffered from acute interstitial pancreatitis (AIP), and 22 patients from necrotizing pancreatitis (NP). Based on the CEH concentrations in the first serum sample obtained in each patient, the sensitivity of CEH for pancreatitis was 98%. From the second day after admission, CEH levels in patients with NP were significantly higher than in patients with AIP. Furthermore, in patients with NP, CEH values remained at a raised level for the following 10 d, whereas a significant decrease of CEH values was noted in patients with AIP. In contrast, total serum amylase activities were higher in patients suffering of AIP than in patients suffering of NP during the observation period. We conclude, that the sensitivity of the CEH test is very high for AP. CEH concentrations remaining at a high level are suggestive of NP, whereas diminishing CEH levels are suggestive of AIP.

Acute Disease↗

Fine-needle aspiration biopsy of pancreatic masses.

The results of fine-needle aspiration biopsy of pancreatic masses in 79 patients (percutaneous with ultrasonic guidance in 23 and peroperative in 56) were evaluated and correlated to survival (follow-up at least 2 years). The original biopsy diagnosis was malignancy in 41 patients, histologically confirmed in 19, all but two of whom died of cancer within 18 months. None of the 22 patients without histologic verification of the primary malignant cytodiagnosis survived for 18 months. The fine-needle biopsy showed benign cells in 30 patients, in 13 of whom histologic diagnosis was obtained, revealing carcinoma in seven. Six of these seven died within a year, but of the six with histologically benign lesion, five survived for more than 2 years. All 17 patients without histologic verification of benign aspiration biopsy findings survived more than 24 months. The biopsy diagnosis was inconclusive in eight patients. Four of them proved to have carcinoma and died within 18 months. The sensitivity of fine-needle aspiration biopsy of the pancreas was 76% in this study and the predictive value for malignancy was 100%.

Adult↗

Parenteral superoxide dismutase plus catalase diminishes pancreatic edema in sodium taurocholate-induced pancreatitis in the rat.

Scavengers of toxic oxygen reduction products have been reported to reduce the inflammatory reaction in some models of pancreatitis. In a blinded study, the effect of parenteral pretreatment with superoxide dismutase plus catalase was compared with placebo on pancreatitis induced in rats by infusion of 0.25% or 2% sodium taurocholate into the hepatopancreatic duct. The degree of inflammation was assessed by macroscopic examination of the pancreas, dry/wet weight ratios of pancreatic specimens, amylase activity in plasma and peritoneal exudate, the weight of the exudate, and its content of total protein. All parameters were indicative of a more severe inflammation in rats given the higher concentration of sodium taurocholate. The only significant effect of the superoxide dismutase plus catalase treatment was a moderate reduction of the dry/wet weight ratio, i.e., pancreatic edema, in rats given 2% sodium taurocholate. Our results indicate that toxic oxygen reduction products, available for interception by parenterally administered superoxide dismutase plus catalase, are of only minor importance in the pathogenesis of sodium taurocholate-induced pancreatitis in the rat.

Amylases↗

Carboxylic ester hydrolase: a serum marker of acute pancreatitis.

By use of an enzyme-linked immunosorbent assay we established serum reference values of carboxylic ester hydrolase, a pancreatic secretory lipolytic enzyme, and explored to see if a raised serum level is indicative of acute pancreatitis. Postoperative elevation of carboxylic ester hydrolase was observed in seven out of ten patients who underwent pancreatic surgery. Serum levels of carboxylic ester hydrolase and amylase were determined in 129 patients admitted due to abdominal emergency conditions. Amylase was elevated in 27 patients, and in 20 of these raised carboxylic ester hydrolase levels affirmed the diagnosis acute pancreatitis. In five out of the seven patients with elevated amylase alone no etiologic factor of acute pancreatitis was found. Another 11 patients had raised carboxylic ester hydrolase levels without concomitant elevation of amylase. In all these patients, a likely cause of pancreatic inflammation was identifiable. Hence, a raised carboxylic ester hydrolase level, even in presence of normal amylase, could be indicative of acute pancreatic inflammation.

Abdomen↗

Serum levels of the carbohydrate antigen CA-50 in pancreatic disease.

A monoclonal antibody (C 50) was recently produced by immunization with a colorectal cell line defining the tumour associated carbohydrate antigen CA-50. In previous studies CA-50 in serum has been elevated in 60-70% of patients with gastrointestinal carcinomas. This study surveys the serum levels of CA-50, as determined by a radioimmunoassay, in pancreatic disease. Elevated levels of CA-50 were found in 22 of the 24 patients with carcinoma of the exocrine pancreas, in one of eight patients with chronic pancreatitis, and in six of fourteen attacks (41%) of acute pancreatitis. The serum CA-50 antigen, as determined by the assay employed here, has a high sensitivity (92%) for exocrine pancreatic carcinoma. Only patients with malignant disease had CA-50 values exceeding 43 units per ml. In 58% of the patients with pancreatic carcinoma (14/24), CA-50 values surpassed 43 units per ml. In the presence of a pancreatic mass, marked elevation seems to support diagnosis of carcinoma. The low positive predictive value makes the assay unsuitable as a screening test for detection of pancreatic carcinoma in a general population.

Acute Disease↗

The continuing challenge of the negative appendix.

A 15-20% negative appendix rate at emergency appendectomy is considered compatible with appropriate aggressiveness of approach for avoidance of perforation and heightened morbidity rate. But the morbidity rate after negative exploration has been estimated as high as 15%. We compared the morbidity rate after emergency appendectomy among patients with acute appendicitis with that in patients with nonacute appendiceal pathology or with normal appendix. Local septic complications (wound infection and/or intraabdominal abscess) were significantly more common in perforative appendicitis than in nonperforative or in cases without appendicitis. Excluding perforative appendicitis, the incidence of such complications did not differ significantly between the other diagnostic groups. The incidence of other complications was evenly distributed among all groups. A scoring system--possibly computer-aided--taking into account predictive factors in appendicitis, combined with careful in-hospital observation, would probably reduce the negative exploration rate in suspected acute appendicitis without increasing the perforation and morbidity rates.

Acute Disease↗

On the source of bile salt-stimulated lipase in human milk: a study based on serum concentrations as determined by sandwich enzyme-linked immunosorbent assay technique.

Human milk contains a bile salt-stimulated lipase (BSSL) which is considered to contribute significantly to lipid digestion in newborns. Human pancreatic juice contains an enzyme, carboxyl ester hydrolase (CEH), that is immunochemically and functionally identical to the milk enzyme. It has not been clear, however, whether the milk enzyme is synthesized within the mammary gland or whether the pancreatic enzyme is transported to the mammary gland for secretion. In this study we describe an enzyme-linked immunosorbent assay (ELISA) for determinations of BSSL and CEH in serum. Serum samples from healthy adults of both sexes contain significant amounts of enzyme (3.2 +/- 1.7 micrograms/L). Lactating women did not have higher serum levels, which would be expected if the milk enzyme were a product of the pancreas, and it was calculated that the concentrations found could not sufficiently account for the amounts secreted in the milk. We therefore conclude that BSSL is synthesized within the mammary gland. This conclusion is further strengthened by our findings that serum of breast-fed newborns contains very little if any enzyme. Since macromolecular absorption is high early in life, and witch's milk contains high enzyme levels, again one would expect high serum levels if BSSL were a pancreatic product.

Adult↗