The fecal chymotrypsin photometric assay in the evaluation of exocrine pancreatic capacity. Comparison with other direct and indirect pancreatic function tests.

Fecal chymotrypsin (FCT) has been measured by a new photometric method (Monotest Chymotrypsin; Boehringer, Mannheim) in 78 patients: 44 with chronic pancreatitis and 34 not affected by any pancreatic disease. The results were compared with those from other tests of pancreatic secretory (secretin-cerulein test) and digestive [serum and urinary p-aminobenzoic acid (PABA) and pancreolauryl] capacity. When FCT values were severely reduced (below 6.7 U/g), from 90 to 100% of the patients also presented abnormal pancreatic secretory and digestive capacity. On the other hand, 87% of the patients with normal FCT (above 20 U/g) presented normal secretory and digestive capacity. Patients with intermediate FCT values (between 6.7 and 20 U/g) showed normal or abnormal pancreatic secretory and digestive capacity with the same probability. Therefore, FCT, carried out as a first test, seems to identify subjects that need no further pancreatic function tests (normal and severely impaired FCT) and patients who need other more complex functional investigations (intermediate FCT values).

A clinical evaluation of monoclonal (CA19-9, CA50, CA12-5) and polyclonal (CEA, TPA) antibody-defined antigens for the diagnosis of pancreatic cancer.

We measured in 193 patients, admitted to our wards for symptoms and signs suggestive of pancreatic or digestive malignancy, the serum levels of five tumor-associated antigens (CA 19-9, CA 50, CA 125, TPA, CEA) and we evaluated their diagnostic accuracy both when used alone and in combination. For CA 19-9 and CA 50 a sensitivity for pancreatic cancer as high as 92 and 88%, respectively, and specificity of 91.8% were found. A lower sensitivity vs. pancreatic cancer was found for the other tumor markers, and vs. the other digestive and nondigestive malignancies for all tumor markers (apart for CA 19-9 and CA 50 vs. biliary carcinomas). As for the combined assays, the best figures were found vs. pancreatic cancer for CA 19-9 plus CA 50, CA 50 plus CEA, CA 50 plus CA 125; a sensitivity by far worse vs. the other gastrointestinal cancers was found for all the possible combinations. We conclude that in selected symptomatic patients some tumor-marker determinations can be useful in identifying those with a high probability of harboring a pancreatic cancer, to be further studied or operated upon. The clinical relevance of this in patients already symptomatic is at present unclear.

Prothrombotic effects and clinical implications of third-generation oral contraceptives use.

Although the use of oral contraceptives has been frequently associated with an increased risk of thromboembolic events, definitive prothrombotic mechanisms have not so far been fully elucidated. The aim of our investigation was the evaluation of the activities of antithrombin, protein C, protein S and the resistance to activated protein C in 137 healthy users of third-generation oral contraceptives and in 170 healthy women who were not consuming oral contraceptives. Women on oral contraceptives showed a marked prothrombotic pattern, characterized by reduced activities of antithrombin and protein S, and increased resistance to activated protein C. Nearby 50% of oral contraceptive users displayed activities of protein S below the lower value of the reference range (controls, 10%; P < 0.001). No significant differences were observed between two progestagens (desogestrel or gestodene) on the coagulation parameters tested. We believe that, due to the adverse effect on haemostasis, the administration of third-generation oral contraceptives should be carefully considered in women carrying prothrombotic abnormalities.

Resistance to activated protein C, associated with oral contraceptives use; effect of formulations, duration of assumption, and doses of oestro-progestins.

Resistance to activated protein C (APC-R) is at present considered the most frequent laboratory abnormality in patients with deep vein thrombosis. An increased risk for venous thrombosis is associated with the use of oral contraceptives (OCs). We recently described a statistically significant association between APC-R status and oral contraceptives use in a healthy group of women. We re-evaluated 50 healthy women taking low-dose combination OCs in order to consider a possible correlation between the APC sensitivity ratio (APC-SR) and different oral contraceptive formulations. Seven women showed an APC ratio < or = 2 (APC-resistant). Only one of the seven women was found to be heterozygous for Leiden factor V mutation. We observed no significant differences between normally sensitive and APC-resistant women in terms of duration of OC use, amount of estrogenic or progestogenic dose, or type of formulation. We conclude that APC-resistance associated with oral contraceptives use seems to occur only in predisposed subjects (in our results, about 12% of the healthy population).

Effect of graded doses of PGE2 on pancreatic exocrine secretion of bicarbonate, chymotrypsin and cyclic nucleotides during i.v. infusion of secretin in man.

We have previously reported that PGE2 inhibits pancreatic enzyme secretion during Secretin-Caerulein infusion, but differing results have also been reported. In this study 10 tests were performed in 5 healthy volunteers as follows: each subject received secretin (GIH) 2 CU/Kg-h by continuous infusion for 2 hours and, several days later, Secretin at the same dose plus PGE2 (Upjohn) in step-wise doses (0.04-0.08-0.12 gamma/Kg min) increasing every thirty min form 30' to 120' min. Duodenal juice was collected in 10 min samples. The volume of each sample was recorded and bicarbonate, chymotrypsin, cAMP and cGMP contents were determined. Statistical evaluation was performed by Student's "t" test for paired data and the regression test. PGE2 significantly decreased chymotrypsin concentration under Secretin. Both cyclic AMP and GMP Secretin-induced secretions were significantly increased by the highest dose of PGE2. No correlation was found in the behaviour of bicarbonate, chymotrypsin and cyclic nucleotides, but it must be noted that our data concern duodenal contents and not pure pancreatic secretion.

Urinary PABA recovery after oral N-benzoyl-L-tyrosyl-PABA administration combined with various exocrine pancreatic stimulants.

Eleven healthy volunteers (C) and nine patients affected by chronic relapsing pancreatitis (CP) were administered N-Benzoyl-L-Tyrosyl-PABA orally, at a dose of 150 mg combined, on different days, with: 1) water alone (schedule a); 2) Lundh meal (schedule b); 3) Secretin-Caerulein by i.v. infusion (0.5 CU/kg/hr and 75 ng/kg/hr respectively) (schedule c); 4) Caerulein by i.m. injection (300 ng/kg) (schedule d). The mean urinary PABA recovery in CP was lower than in C with all the schedules, but this was statistically significant only with schedules a and c (P less than 0.02 and P less than 0.05 respectively). With respect to b, c, and d, the mean urinary PABA recovery seemed to increase both in C and in CP as compared with schedule a, but only in the CP group with schedule b was the increase statistically significant (P less than 0.05). The present data show that the exocrine pancreatic stimulants do not improve the reliability of the PABA test.

Effect of carprofen and indomethacin on gastric function and the content of prostaglandins E2 and F2 alpha in human gastric juice.

The effect of indomethacin (2 X 50 mg daily) and carprofen (2 X 150 mg daily) on gastric secretion and the generation of prostaglandins PGE2 and PGF2 alpha in gastric juice, was investigated in a single blind cross-over study in eight healthy volunteers lasting one week. We observed no statistically significant change in basal and pentagastrin-stimulated gastric secretory parameters (outputs of gastric acid, N-acetyl-neuraminic acid and pepsin) before and after treatment with indomethacin and carprofen. However, an inhibitory effect was found on the output of PGE2 and PGF2 alpha after pentagastrin stimulation. While both drugs diminished the output of PGF2 alpha to a similar extent, carprofen exerted a markedly weaker inhibitory effect on the output of PGE2 than did indomethacin. It is suggested that the gastric tolerability of non-steroidal anti-inflammatory drugs (NSAIDs) is related to their inhibitory potency on PGE2 formation, in the sense that weak inhibitors of PGE2 cause less damage to the gastric mucosa than do strong inhibitors.

[Modification of an experimental model of chronic pancreatic and biliary fistula in the minipig (author's transl)]. / Modifiche di un modello sperimentale di fistola pancreatica e biliare cronica nel minipig.

An improvement in Corring's experimental model in the minipig is described. The model requires: -- a complete diversion of the biliopancreatic secretion and the possibility of its reintroduction into the duodenum; -- a particular anaesthesiological, technical and management problems taken up during the course of the research. Data are also given about basal pancreatic and biliary secretions in this particular experimental model.

Lipoprotein(a) concentration is not associated with venous thromboembolism in a case control study.

BACKGROUND AND OBJECTIVE: Lipoprotein(a) is an LDL-like particle displaying strong athero-thrombotic properties. Although Lp(a) plays a pivotal role in the genesis and progression of thrombosis in the arterial district, its role in promoting thrombosis in the venous district is still unclear. DESIGN AND METHODS: To give further insight into the thrombotic potential of Lp(a), 100 potentially eligible consecutive outpatients who had suffered from previous episodes of venous thrombosis (deep vein thrombosis with or without pulmonary embolism) were enrolled into the study. Thirty-six of these patients who did not fulfil the entry criteria were then excluded from the study. The concentration of Lp(a) was thus measured in 64 patients, and compared to that of 64 control subjects, matched for sex (p=0.46), age (p=0.25) and pharmacological treatment; no subject belonging to the control group had a familial or personal history of venous thromboembolism. Exclusion criteria for both groups included: diabetes mellitus, liver or kidney diseases and malignancy, as established by both laboratory analysis and physical examination. To rule out false elevations of Lp(a) due to the presence of a concurrent acute phase response, C reactive protein (CRP) was measured in both groups using a commercial immunonephelometric assay. RESULTS: No statistically significant differences were observed in the median Lp(a) concentration between patients and controls (median: 69 vs 83 mg/L, respectively; p=0.34). Neither were any significant differences found between patients who had suffered from deep venous thrombosis with (n=18) or without (n=46) pulmonary embolism (median: 73 vs 69 mg/L, respectively; p=0. 83). The concentration of CRP did not differ significantly between cases and controls (median: 1.8 vs 2.3 g/L, respectively; p=0.37). INTERPRETATION AND CONCLUSIONS: Although there are several plausible biological mechanisms to explain the strong thrombogenicity of Lp(a) in vitro, we failed to demonstrate a convincing association between Lp(a) and thrombosis in the venous district. Besides the proven prothrombotic role of Lp(a) in some selected clinical settings, it is thus conceivable that the contribution of Lp(a) to genesis and progression of the venous thrombosis might be marginal or efficiently counterbalanced in vivo. The clinical usefulness of including the measurement of Lp(a) among the screening tests for thrombophilic patients, therefore, remains questionable.

A microplate-based colorimetric assay of the total peroxyl radical trapping capability of human plasma.

We developed a colorimetric assay estimating the radical-scavenging activity of human plasma. The test is based on a measure, in 96-well microplates at 450 nm, of the bleaching of carotenoid crocin by peroxyl radicals generated during thermal decomposition of 2, 2'-azobis-(2-amidinopopane) dihydrochloride (ABAP). The inhibition of this bleaching is a function of the antioxidant power of substances added to incubation mixture. We determined the optimal conditions for a sensitive, rapid, and reproducible assay of 50% inhibitory capacity (IC50) of a range of antioxidant substances and of plasma. Only a total of 200 microl of plasma is required in a complete dose-inhibition curve. The IC50 of normal human plasma resulted of 2.70 microl of plasma/250 microl assay volume. The total antioxidant capability (TAC) of plasma was defined as the reciprocal of IC50 and its value in a group of 19 healthy adults resulted in 0. 369 +/- 0.06. Intraassay and interassay coefficients of variation of plasma TAC were 6.13 and 4.80%, respectively. Measurement of samples with different uric acid concentration showed that antioxidant activity of uric acid accounts for approximately two-thirds of TAC.

Clinical utility of a wheat-germ precipitation assay for determination of bone alkaline phosphatase concentrations in patients with different metabolic bone diseases.

Bone alkaline phosphatase was evaluated by wheat-germ lectin precipitation in several clinical conditions. The study included 33 premenopausal healthy women, 46 postmenopausal apparently healthy women, 19 growing children, 24 patients with Paget's disease, 31 patients with primary hyperparathyroidism and 66 patients with hepatobiliary diseases. In postmenopausal women the mean T score (i.e.: the number of SD below or above the mean for premenopausal women) was 2.6 +/- 1.3 (SD) for bone alkaline phosphatase and 1.61 +/- 1.21 for total alkaline phosphatase (p < 0.001). The T score for bone alkaline phosphatase provided a better discrimination from normals for both Paget's disease (22.1 +/- 27.8 versus 12.8 +/- 16 p < 0.001) and primary hyperparathyroidism (8.2 +/- 4.3 versus 4.6 +/- 3.7 p < 0.005 for bone alkaline phosphatase and total alkaline phosphatase respectively). After treatment with intravenous bisphosphonate the percent decrease of bone alkaline phosphatase was larger than that of total alkaline phosphatase both in patients with Paget's disease (-46% versus -72% p < 0.01) and in patients with primary hyperparathyroidism (-21% versus -47% p < 0.02) and an estimate of the precision (delta mean/SD of the delta mean) for bone alkaline phosphatase was 1.9-3.7 times higher than that of total alkaline phosphatase. In twelve osteoporotic patients treated for six months with oral alendronate the decrease in bone turnover was detected with significantly higher precision with bone alkaline phosphatase than with total alkaline phosphatase (p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of acute exercise on some haematological parameters and neutrophil functions in active and inactive subjects.

In this work we studied the possible effects of acute exercise on some haematological parameters and on some functions of neutrophils in seven active and six inactive subjects. Physical exercise (10 min on a cycle ergometer at a heart rate of 150 beats.min-1) induced a significant increase in total leucocyte, lymphocyte and neutrophil concentrations in active subjects; serum iron and ferritin concentrations were lower in active compared to inactive subjects. Cellular adhesion, bactericidal activity and superoxide anion production did not change after exercise, while we also observed some differences between active and inactive subjects before exercise. In particular, the neutrophils from active subjects showed a significantly higher percentage of adhesion, higher bactericidal activity and lower superoxide anion production. In conclusion, the training induced changes in some neutrophil functions, while acute exercise influenced, overall, leucocyte concentrations.

Lipase latex test for acute abdominal pain: comparison with serum lipase, trypsin, elastase and amylase.

The diagnostic capacity of a semiquantitative latex test for lipase measurement was compared with the measurement of other pancreatic enzymes in 100 consecutive patients admitted to a general hospital for recent onset of severe abdominal pain. Positive results of the test were found in two patients with acute pancreatitis, and in one out of three chronic pancreatitis relapses. The test yielded false-positive results only in two patients who had no apparent pancreatic involvement. A marginal increase in other pancreatic enzymes was found in a few patients with acute biliary or appendicular problems. In conclusion, the lipase latex test can be suggested in an emergency setting as a quick and reliable alternative to serum amylase to rule out a diagnosis of acute pancreatitis.

Acute anti-inflammatory activity and gastrointestinal tolerability of diclofenac and nitrofenac.

Diclofenac and its derivative nitrofenac were compared to test their anti-inflammatory efficacy and gastrointestinal toxicity in rats. A similar good anti-inflammatory activity of the two drugs was observed in carrageenan oedema and a marked gastrointestinal toxicity was induced by diclofenac, while nitrofenac failed to produce gastric damage even with very high doses (50 and 100 mg/kg). The lack of the gastric ulcers in rats treated with nitrofenac could be due to the absorption of the drug as an inactive inhibitor of PG synthesis and/or to the fact that probably nitric oxide is released in the intestine and plays an important protective role in maintaining the tissue integrity.

Measuring gastric PGE2 release in healthy and alcoholic subjects after ethanol stimulation.

The aim of this work was to study the effect of 20% and 40% ethanol, administered acutely, on gastric PGE2 release in normal subjects and alcoholics. Ethanol 20% did not modify the release of PGE2 into the gastric juice, whereas 40% ethanol increased PGE2 release only in healthy subjects. The basal PGE2 levels were higher in alcoholic patients.

Pancreatic exocrine function in rosacea.

As some rosacea patients complain of gastrointestinal troubles and the administration of pancreatic extracts ameliorates both dyspepsia and skin lesions, the pancreatic exocrine function in 21 subjects affected with rosacea has been investigated by means of the secretin-cerulein infusion test. 21 healthy controls have been studied for comparison. No difference was found between rosacea and control subjects for flow rate, bicarbonate and chymotrypsin concentration and output, while lipase concentration and output was significantly lower in rosacea patients, with a decrease ranging from 18.5 to 66% of normal values. Therefore, a deficient lipase secretion could be responsible, at least partly, for the clinical manifestations of rosacea.