Origin of serum catalase activity in acute pancreatitis

Serum catalase activity was examined in 96 patients with the oedematous form and in 15 patients with the necrotic form of acute pancreatitis. Total catalase release into plasma was estimated to be 2,140 +/- 947 kU and 4,764 +/- 1,505 kU, respectively. The g equivalents of pancreas were 163 +/- 72 g and 362 +/- 133 g, being 2.03-fold and 4.52-fold higher than the whole mass of pancreas indicating the nonpancreatic origin of the total increase of serum catalase. In both types of acute pancreatitis serum haemoglobin, haematin, haptoglobin and LDH values supported the presence of haemolysis. The volumes of blood were 22.6 +/- 10.1 ml and 50.4 +/- 15.9 ml which are only 0.41% and 0.91% of the total blood volume. Taking these findings into account, in acute pancreatitis the major part of increase of serum catalase can be explained by its release from the erythrocytes.     

Plasma leptin levels in rats with pancreatitis

Diagnosis of pancreatitis is based on the determination of serum amylase and lipase levels. However, recent identification of specific leptin receptors in the pancreas suggests that this peptide may also play some roles in the modulation of pancreatic function. The objective of the present study was to investigate the relationship between serum leptin levels and pancreatitis. Thirty male Wistar rats were divided into 3 groups: the control group, acute pancreatitis group and chronic pancreatitis group. Pancreatitis was induced by injection of ethyl alcohol into the common biliary duct. A sham laparotomy was performed in the control group. Control and acute pancreatitis groups were sacrificed 24 hours later, and chronic pancreatitis group was sacrificed on postoperative day 7. Blood was taken by cardiac puncture for the determination of plasma leptin levels, and the pancreatic tissue was excised for histopathologic confirmation of pancreatitis. Plasma leptin rose significantly from the median of 0.78 +/- 0.12 ng/ml in the control group to 1.92 +/- 0.10 ng/ml and 1.86 +/- 0.13 ng/ml in acute and chronic pancreatitis groups, respectively (p < 0.001, for both). There was no significant difference in the plasma leptin levels between the acute pancreatitis group and the chronic pancreatitis group (p > 0.05). These findings confirm that leptin has a role in pancreas inflammation, and the inflamed tissue can be the source of local production of leptin.     

Atrial natriuretic peptide in human essential hypertension

We measured the circulating levels of atrial natriuretic peptide (ANP) in 62 patients with untreated uncomplicated essential hypertension and in 30 normotensive subjects. In the hypertensive patients, mean systolic and diastolic blood pressures were 148 and 101 mm Hg, respectively, and the mean heart rate was 73 beats/min. ANP concentrations were not elevated in the hypertensive group but were actually decreased slightly over those of the control group (27.4 +/- 1.8 pg/ml versus 35.3 +/- 2.4 pg/ml [P less than 0.02]). No relationship was found between ANP levels and diastolic blood pressure, plasma renin activity, urinary sodium excretion, or serum creatinine level. In 8 of the 62 patients with essential hypertension, 6 weeks of treatment with a dihydropyridine calcium channel blocker, nitrendipine, significantly reduced plasma ANP levels from 28.6 +/- 4.3 pg/ml to 18.7 +/- 1.8 pg/ml (P less than 0.05). In 17 additional patients treated with the hypotensive agent ketanserin, ANP levels were not significantly reduced after treatment. Thus, this study demonstrates that circulating plasma ANP levels are not increased but are slightly decreased in patients with uncomplicated essential hypertension in comparison with normotensive subjects. Furthermore, antihypertensive treatment with a calcium channel antagonist reduced plasma levels of ANP.     

Contribution of the pancreas to circulating somatostatin-like immunoreactivity in the normal dog.

These studies were performed to assess the contribution of the pancreas to the somatostatin-like immunoreactivity (SLI) circulating in arterial and portal venous plasma. Basal SLI concentrations in arterial, pancreatic venous, and portal venous plasma were 95 +/- 9, 277 +/- 32, and 130 +/- 12 pg/ml, (means +/- SEM), respectively. Measurement of pancreatic and portal venous blood flow (5 +/- 1 vs. 365 +/- 46 ml/min) and hematocrit allowed calculation of net, base-line SLI output from the right lobe of the pancreas (521 +/- 104 pg/min) and from the gastrointestinal tract (8,088 +/- 1,487 pg/min), which suggested that the contribution of the pancreas to circulating SLI was minor when the D cells were not stimulated. To stimulate the secretion of SLI from both pancreatic and nonpancreatic sources, isoproterenol, a beta-adrenergic agonist, was infused intravenously for 1 h into six anesthetized dogs. Arterial SLI increased by 52 +/- 9 pg/ml; superior pancreatico-duodenal venous SLI increased by 380 +/- 95 pg/ml; portal venous SLI increased by 134 +/- 14 pg/ml. Pancreatic venous blood flow remained unchanged at 5 +/- 1 ml/min, but portal venous blood flow increased to 522 +/- 62 ml/min. SLI output from the right lobe of the pancreas increased by 684 +/- 227 pg/min and that from the gastrointestinal tract increased by 23,911 +/- 3,197 pg/min, again suggesting that the pancreas was a minor source of circulating SLI even when the D cells were stimulated. We conclude that the measurement of arterial-venous SLI concentrations, in the absence of measurements of organ blood flow, can give a false impression of the organ's contributions of circulating SLI. To verify that the contribution of the pancreas was negligible, six dogs received an acute pancreatectomy and then an intravenous infusion of isoproterenol at the same rate. In these dogs, both the base-line level of SLI in arterial plasma (109 +/- 12 pg/ml) and the increment during isoproterenol (56 +/- 8 pg/ml) were similar to those of normal dogs. Likewise, in pancreatectomized dogs both the base-line level of SLI in portal venous plasma (129 +/- 16 pg/ml) and the increment during isoproterenol (174 +/- 34 pg/ml) were similar to those of normal dogs. We conclude that, in normal dogs, the pancreas makes a negligible contribution to the basal and stimulated level of SLI in arterial and portal venous plasma and therefore that these levels should not be used as an index of secretory activity of the pancreatic D cells.     

lnterleukin-8 and neutrophil activation in acute pancreatitis

It has been suggested that leucocytes play an important role in the pathogenesis of complicated pancreatitis. Indeed, increased plasma concentrations of neutrophil elastase as a marker of neutrophil activation could be detected in patients with a severe course of the disease. Recently, interleukin-8 (IL-8) has been described as a novel neutrophil activating peptide. To determine the role of IL-8 in acute pancreatitis we measured its serum concentrations by a specific enzyme-linked immunosorbent assay in 10 patients with acute pancreatitis daily during the first week of hospitalization. IL-8 levels were compared with plasma concentrations of neutrophil elastase and the clinical course of the disease. Three of the patients had uncomplicated pancreatitis, while seven showed various extrapancreatic complications. Patients with complicated pancreatitis had statistically significant (P less than 0.05) higher mean values of IL-8 (121 +/- 41 pg/ml-1 vs. 13 +/- 6 pg ml-1, mean +/- SEM) and neutrophil elastase (547 +/- 35 ng ml-1 vs. 250 +/- 20 ng ml-1) than patients with uncomplicated disease. There was a positive correlation (r = 0.52, P less than 0.0001) between IL-8 and neutrophil elastase in the lower concentration range of IL-8 (less than 100 pg ml-1). At IL-8 levels greater than 100 pg ml-1 neutrophil elastase was always greatly elevated; however, under these conditions the relationship between IL-8 and elastase was no longer linear. No measurable IL-8 concentrations were found when plasma elastase was less than 200 ng ml-1. During follow-up, initially elevated IL-8 concentrations decreased in correlation with clinical improvement.(ABSTRACT TRUNCATED AT 250 WORDS)     

Hepatic and renal metabolism of somatostatin-like immunoreactivity. Simultaneous assessment in the dog.

The hepatic and renal metabolism of somatostatin-like immunoreactivity (SLI) was assessed simultaneously in an in vivo dog model. The hepatic extraction of this peptide was 29.4 +/- 2.3% and was similar for endogenous and infused exogenous SLI. The renal extraction was 62.3 +/- 5%. The renal clearance of SLI was significantly greater than that of inulin indicating that the peptide is handled by peritubular uptake from postglomerular blood in addition to glomerular filtration. In both organs SLI extraction was not saturable even at arterial concentrations in excess of 100 times physiological range. The overall metabolic clearance rate of SLI was 19.7 +/- 1.6 ml/kg per minute of which 32.7 +/- 4.6% was contributed by hepatic and 37 +/- 4.9% by renal uptake mechanisms. The plasma half disappearance time of exogenously infused SLI was 1.9 +/- 0.3 min. The studies indicate that in the dog, the liver and kidney are both major sites of SLI metabolism, together accounting for 70.0 +/- 8.7% of the metabolic clearance of the peptide.     

TAP和C反应蛋白在急性胰腺炎早期诊断与预后评估中的价值

目的探讨血浆胰蛋白酶原激活肽(TAP)和C反应蛋白(CRP)在急性胰腺炎(AP)早期诊断与预后评估中的价值。方法选取AP患者79例(58例重症患者和21例轻型患者),非急性胰腺炎患者42例作为对照。所有患者于在入院后1、24h、3d抽血测试TAP,重症急性胰腺炎(SAP)组和轻症急性胰腺炎(MAP)组于1、24h、3、5、7d抽血测试CRP,并对结果进行对照分析。结果胰腺炎组与非胰腺炎组相比,TAP明显升高,且SAP组和MAP组之间TAP差异有统计学意义(P0.05);SAP组与MAP组入院1周内各时测点CRP浓度水平比较差异有统计学意义(P0.05)。结论TAP能够早期准确诊断AP,其和CRP动态检测可作为AP患者严重度区分的指标,对AP预后具有良好的预测作用。     

Anesthesia in surgical treatment of the ascending aorta-arch aneurysms

The paper analyzes anesthesiological maintenance of infusion therapy, optimal criteria for effective brain protection, complications and mortality in 42 patients during operations on the ascending portion and arch of the aorta under deep hypothermic circulatory arrest. For this purpose, the patients were divided into 2 groups: Group 1 comprised 20 patients operated on before 1998; Group 2 included 22 patients operated on in 1998 to 2001. In both groups, circulatory arrest lasted 44 +/- 7 min. The patients were cooled to a temperature of 13.5 +/- 0.5 degrees C, to 15 +/- 0.6 degrees C in the nasopharynx. The duration of cooling was 58 +/- 5 and 73 +/- 6 min, respectively; that of warming-up was 70 +/- 8 and 83 +/- 6 min. Investigations have indicated that determination of the optimum brain cooling requires a complex assessment of central temperature values, electroencephalographic monitoring (visual estimation of a curve and quantitative characteristics), SjbO2 and cerebral metabolism. The investigations have shown that the procedure for anesthesiological maintenance and cerebral metabolism is safe and effective even in patients with arrested circulation lasting longer than 60 min. The operative mortality does not depend on the use of circulatory arrest under deep hypothermia and on its duration. Hemodynamic instability due to bleeding, as well as myocardial infarction, marked hemodilution during extracorporeal circulation are major factors that cause an increase in the rates of incidence of complications and mortality. The procedure used for anesthesiological maintenance and infusion therapy, decreased blood loss, and a reduction in the incidence of myocardial infarction could significantly reduce operative mortality. The fact that there were no neurological complications even during prolonged (80-min) circulatory arrest has shown that the brain-protective procedure including both general and regional cooling is reliable and to the extent of the indicated criteria. So is pharmacological protection.     

Decreased production of glutathione in patients with cirrhosis

Studies in animals have demonstrated the central role of the liver in regulating the circulating pool of glutathione (GSH). Most of the hepatic GSH production is released into blood and most of the circulating GSH originates in the liver. We have estimated the production of GSH in eight healthy volunteers and eight patients with cirrhosis by an analysis of the kinetics of plasma GSH. The basal plasma concentrations of free GSH were 9.3 +/- 2.4 microM in healthy volunteers and 3.6 +/- 1.1 microM in cirrhotics (P less than 0.001), and the concentrations of total GSH 16.6 +/- 6.2 microM in control subjects and 7.1 +/- 2.6 microM in cirrhotics (P less than 0.002). The concentration of GSH in the circulating pool depends on the input of GSH into this compartment and is inversely proportional to the volume of distribution of GSH (Vd) and to the fractional rate of elimination of GSH from plasma (kel). Assuming that the kinetics of endogenously produced and exogenously administered GSH are identical, Vd and kel can be calculated from the plasma concentration-time curve of a single i.v. injection of GSH. Both Vd (0.100 +/- 0.044 l kg-1 in controls and 0.131 +/- 0.043 l kg-1 in cirrhotics) and kel (0.2718 +/- 0.0555 min-1 in controls and 0.2912 +/- 0.0781 min-1 in cirrhotics) were identical in the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cholecystokinin and glucose-induced insulinaemia in dogs with and without pancreatic acinar atrophy

The entero-insular hormonal axis was studied in eleven conscious Beagle dogs, loaded with glucose orally and intravenously. In five of them, exocrine pancreatic atrophy was induced by pancreatic duct occlusion with prolamine, and documented by means of the p-amino-benzoic acid test. After oral glucose, the duct-occluded dogs displayed higher blood glucose (log area 4.12 +/- 0.07 versus 3.76 +/- 0.10; p less than 0.01), less plasma insulin (log area 3.56 +/- 0.08 versus 3.99 +/- 0.08; p less than 0.01) and less cholecystokinin-like immunoreactivity (log area 2.64 +/- 0.09 versus 3.10 +/- 0.14; p less than 0.01) than controls. In controls, the peripheral venous insulin concentrations were higher after oral than after isoglycaemic intravenous glucose, and this difference was no longer demonstrable in duct-occluded dogs. In the latter, gel permeation chromatography of pool plasma after oral glucose revealed a relative decrease of cholecystokinin-like immunoreactivity species, which eluted at the positions of sulphated cholecystokinin octapeptide, cholecystokinin-33 and cholecystokinin-39, and at a position intermediate between these two. Also in the duct-occluded animals, intravenous infusion of sulphated cholecystokinin octapeptide, in addition to oral glucose, resulted in an increase in plasma insulin (log area 3.83 +/- 0.10 versus 3.64 +/- 0.06; p less than 0.01) and an improvement in oral glucose tolerance. It is concluded that in the dog 1) the absence of pancreatic acinar tissue is associated with a loss of gastrointestinal factors mediating glucose-induced insulin secretion, and 2) reduction of circulating endogenous cholecystokinin species may account at least in part for this defect.     

Parathyroid hormone-related peptide in plasma of patients with hypercalcemia and malignant lesions.

We developed and validated a radioimmunoassay for circulating human parathyroid hormone-related peptide (PTHrP), based on a commercial antiserum to the synthetic 1-34 fragment of PTHrP, 125I-Tyr degrees-PTHrP(1-34) as radioligand, and prior extraction of the native peptide from plasma with C-2 cartridges. We determined immunoreactive PTHrP concentrations in plasma samples from 48 healthy persons (mean +/- SD, 3.1 +/- 1.0 pmol/liter; range, less than 2 to 5 pmol/liter), 8 patients with primary hyperparathyroidism, 36 patients with hypercalcemia and a concurrent malignant lesion, and 9 normocalcemic patients with cancer and increased serum levels of carcinoembryonic antigen or prostate-specific antigen. PTHrP was normal in samples from patients with primary hyperparathyroidism (3.2 +/- 1.1 pmol/liter), secondary hyperparathyroidism (2.5 +/- 1.3 pmol/liter), and cancer without hypercalcemia (2.4 +/- 1.0 pmol/liter). In contrast, plasma immunoreactive PTHrP levels were increased (6.0 to 85.0 pmol/liter) in 47% of patients with hypercalcemia and cancer of various types, with or without bone metastatic lesions. Large amounts of PTHrP were also found in conditioned medium from cultured human prostatic carcinoma cells. Thus, PTHrP may be a causative factor for hypercalcemia associated with a malignant lesion in at least half of the cases. Measurement of circulating PTHrP may be of differential diagnostic help in hypercalcemic states.     

Influence of exercise on ascorbic acid status in man

1. The response of circulating leucocytes with regard to changes in number, proportion of granulocytes and lymphocytes, as well as changes in the ascorbic acid (AA) concentration of plasma and isolated lymphocytes, were studied in nine men who ran a 21 km race. A marked leucocytosis was noted 5 min after the race, the predominant increase being in granulocytes (P less than 0.001) with smaller relative increases in circulating lymphocytes (P less than 0.01) and platelets (P less than 0.001). Numbers of leucocytes and platelets returned to pre-exercise levels within 24 h after the race. 2. The concentration of AA in plasma increased from 52.7 +/- 4.1 mumol/l before the race to 67.0 +/- 5.3 mumol/l within 5 min after the race (P less than 0.001). This increase in plasma AA concentration was positively correlated with the rise in plasma cortisol concentration during the race (r = 0.89; P less than 0.01). However, within 24 h after the race the plasma concentration of AA fell 20 +/- 4% below pre-exercise values (P less than 0.01) and remained low for at least the next 2 days (P less than 0.05). 3. Lymphocyte AA concentration increased from 15.6 +/- 0.6 to 19.7 +/- 0.9 mumol/g of lymphocyte protein during the race (P less than 0.01) but returned to normal levels within 2 days after the race. 4. It is suggested that the adrenal gland may be the major source of AA efflux into the circulation during exercise.     

Cholecystokinin is a physiological hormonal mediator of fat-induced inhibition of gastric emptying in man

The effect of cholecystokinin-33 on gastric emptying was studied in eight healthy men. The test meal was a firm custard pudding, labelled with 99mTc-Chelex-100 particles. Gastric emptying rate was measured, using a dual-headed gamma camera, and was expressed as the half time of the emptying curve. Plasma cholecystokinin concentrations were determined by radioimmunoassay. Subjects were studied three times: (i) during infusion of saline; during cholecystokinin infusion, (ii) 0.375 IDU kg-1 h-1 and (iii) 0.75 IDU kg-1 h-1. Furthermore, plasma cholecystokinin was determined after a regular meal. During saline, plasma cholecystokinin increased minimally. After the regular meal it increased from 1.6 to 6.5 pmol l-1 at 30 min, decreasing to 5.3 pmol l-1 at 60 min. During the lower and higher doses of cholecystokinin it increased from 1.0 and 1.4 to 4.5 and 7.3 pmol l-1, respectively. The lower and higher doses significantly (P less than 0.05) increased half emptying time, from 45 +/- 8 to 86 +/- 17 and 198 +/- 50 min, respectively. Cholecystokinin is most likely a physiological hormonal mediator of fat-induced inhibition of gastric emptying.     

Clearance of human brain natriuretic peptide in rabbits; effect of the kidney, the natriuretic peptide clearance receptor, and peptidase activity

Although the synthetic version of the cardiac peptide human brain natriuretic peptide (hBNP) has demonstrated beneficial cardiovascular effects in clinical studies, little is known about mechanisms governing its elimination from the blood. This study measured the role of the kidney, the natriuretic peptide clearance (NP-C) receptor, and peptidase digestion on the elimination of synthetic hBNP from the plasma compartment of rabbits. The estimated plasma steady state resulting from a continuous i.v. infusion was achieved within 50 min and was related in a linear manner with the infusion rate of the drug. Complete restriction of kidney blood flow by bilateral suture-ligation of the renal arteries compared with sham-treated animals reduced the clearance of hBNP by approximately half (24 +/- 9 ml/min versus 47 +/- 14 ml/min, respectively, p <. 007). Pharmacological blockade of the NP-C receptor with a clearance receptor-specific analog of atrial natriuretic peptide increased in a statistically significant and dose-related manner the plasma steady-state level of hBNP during continuous i.v. infusion of hBNP (maximum effect of 1.9 +/- 0.3-fold, p <.01). The peptidase inhibitor phosphoramidon increased in a dose-related manner the plasma steady-state level of hBNP 1.7 +/- 0.4-fold during continuous i.v. infusion of hBNP in rabbits. These data suggest that the kidney, the NP-C receptor, and peptidases are all important in the elimination of hBNP from the plasma compartment.     

Plasma concentrations of atrial natriuretic peptide in various diseases

Using a radioimmunoassay for atrial natriuretic peptide (ANP) we studied plasma concentrations of immunoreactive ANP in order to investigate the pathophysiological role of ANP in patients with various diseases. Plasma ANP levels were elevated in patients with congestive heart failure (394 +/- 260 pg/ml, n = 8) and chronic renal failure (219 +/- 86 pg/ml, n = 11). In patients undergoing hemodialysis plasma ANP levels were markedly high and decreased after hemodialysis from 433 +/- 166 pg/ml to 204 +/- 92 pg/ml (n = 11). ANP was removed from blood to dialysate (21 +/- 13 pg/ml of dialysate, n = 6, dialysate flow: 500 ml/min). Plasma ANP level was conversely correlated with creatinine clearance (r = -0.812, p less than 0.001) in patients with renal diseases (n = 29). In patients with atrial fibrillation, pace maker implantation, lung disease, chronic glomerulonephritis, nephrotic syndrome, essential hypertension, liver disease and cerebrovascular disease, plasma ANP levels were not significantly different from those in normal subjects (70 +/- 32 pg/ml, n = 28). These results suggest that ANP may be a circulating hormone playing pathophysiological roles in congestive heart failure and chronic renal failure.     

Therapeutic plasma exchange in patients with chylomicronemia syndrome complicated by acute pancreatitis.

Chylomicronemia syndrome (CMS) is a rare disorder characterized by the presence of chylomicrons in the fasting state causing a milky appearance of plasma, eruptive xanthomas, and hepatosplenomegaly; an acute and potentially life threatening complication is severe acute pancreatitis. The underlying defects are inborn errors of metabolism such as deficiencies of lipoprotein lipase (LPL) or apoprotein C-II (apo C-II) as well as familial hypertriglyceridemia. Moreover, CMS can be precipitated when mild hypertriglyceridemia is exacerbated by additional factors such diabetes mellitus, ethanol abuse, or pregnancy. The purpose of the present study was to retrospectively analyze the results of therapeutic plasma exchange (TPE) in 5 patients transferred to our hospital for severe acute pancreatitis due to chylomicronemia syndrome. In a total of 7 TPE sessions, on average 3,286 +/- 247 ml of plasma (i.e., about 1 patient plasma volume) were treated per session. Triglyceride (TG) levels were decreased from 4,972 +/- 2,469 mg/dl on admission to 1,614 +/- 1,276 mg/dl (-70%) after the TPE sessions, and a further decrease was achieved by conservative treatment. Part of the TG reducing effect of the treatment was probably due to heparin induced lipolysis. Acute pancreatitis was resolved in all cases, and 1 pregnant patient delivered without problems at term. In summary, 1 or 2 TPE sessions sufficed to substantially decrease the bulk of triglycerides in acutely exacerbated chylomicronemia syndrome causing a rapid resolution of acute severe pancreatitis.     

The elimination of trypsin--alpha-macroglobulin complexes from the blood circulation in pigs during acute pancreatitis and after massive intravenous trypsin infusion

The elimination from plasma of intravenously injected 125I-labelled trypsin-alpha-macroglobulin complexes was studied in both healthy and diseased, anaesthetized pigs. The t1/2 for the 125I-labelled complexes was 5-10 min in healthy pigs as well as in two groups of pancreatitis pigs. Pre-loading of the eliminating capacity by massive intravenous trypsin infusion, raised t1/2 to 80-100 min. Thus, the eliminating capacity seems to be saturable. Elimination of the complexes from the blood circulation occurred within 4-5 h. Even massive intravenous amounts of trypsin-alpha-macroglobulin complexes gave no demonstrable complement or kinin activation. Neither were other deleterious effects seen during the experiment or during 7 days of follow-up. The results indicate that treatment of acute pancreatitis in humans with alpha 2-macroglobulin might be possible, without any danger arising from the protease-alpha 2-macroglobulin complexes formed.     

Use of intravenous microdialysis to monitor changes in serotonin release and metabolism induced by cisplatin in cancer patients: comparative effects of granisetron and ondansetron

Serotonin [5-hydroxytryptamine (5-HT)] is involved in the production of emesis associated with cisplatin treatment. Serotonin released from intestinal enterochromaffin cells may act either directly on vagal afferents and/or pass to the circulation and stimulate central emetic centers. However, the role for circulating 5-HT has not been determined. In this study, i.v. microdialysis probes were used to investigate 1) cisplatin-induced changes in 5-HT release and metabolism assessed through changes in blood dialysate levels of 5-HT and 5-hydroxyindoleacetic acid (5-HIAA), 2) whether free 5-HT in blood increases after cisplatin, and 3) whether granisetron and ondansetron exert different effects on cisplatin-induced 5-HT release and metabolism. Control experiments conducted in 10 healthy volunteers revealed stable 5-HT and 5-HIAA dialysate levels for a period of 6 h. In patients with cancer (n = 16), baseline blood dialysate 5-HIAA concentrations averaged 2.98 +/- 0.38 ng/ml, which were equivalent to a total of 94 +/- 10 pg in the 30-min collection period at a flow rate of 1 microl/min. Cisplatin (89 +/- 2.9 mg of cisplatin/m(2)) produced a gradual increase in blood dialysate 5-HIAA levels (104 +/- 4% increase at 4 h). Increases in dialysate 5-HIAA were associated with increases in the urinary excretion of this metabolite. After cisplatin, dialysate 5-HIAA levels increased to 5.89 +/- 0.5 ng/ml in granisetron and to 5.27 +/- 0.9 ng/ml in ondansetron-treated patients (P >.1). Similar time courses and percentages of increase in blood dialysate and urinary 5-HIAA levels were observed in ondansetron- and granisetron-treated patients. Contrary to 5-HIAA, no significant increases in dialysate 5-HT were observed from 2 to 8 h after cisplatin either for the total group or for each of the groups separately. In conclusion, i.v. microdialysis probes coupled to HPLC-EC allowed the continuous monitoring of free-5-HT and 5-HIAA in blood. Cisplatin-induced increases in blood 5-HIAA were not associated with increases in 5-HT blood dialysates. These results argue against a possible action of free 5-HT in plasma on the chemoreceptor trigger zone (unprotected from the blood brain barrier) but support the view that 5-HT released within the intestinal wall triggers emesis after cisplatin. Our results argue against the view that at clinically effective doses, granisetron and ondansetron exert different actions on cisplatin-induced 5-HT release and metabolism.     

Plasma trypsin in chronic pancreatitis and pancreatic adenocarcinoma.

We have used a simple and precise radioimmunoassay to measure trypsin in human plasma. Fasting plasma trypsin concentrations were extremely low in patients with chronic pancreatitis with steatorrhoea (5 +/- 2 ng/ml) when compared to healthy controls (86 +/- 7 ng/ml, p less than 0.001). In patients with chronic pancreatitis but no steatorrhoea basal plasma trypsin levels were similar to those of the normal controls (99 +/- 25 ng/ml). A small but significant postprandial rise in plasma trypsin concentrations was observed in normal subjects (mean increment 15 +/- 4%, p less than 0.005, paired t test) but was absent in patients with chronic pancreatitis with steatorrhoea. In contrast to exocrine deficient chronic pancreatitis, other malabsorptive conditions associated with steatorrhoea (active coeliac disease and acute tropical sprue) demonstrated mean fasting trypsin concentrations similar to controls. Patients with adenocarcinoma of the pancreas had basal trypsin concentrations similar to healthy subjects as did patients with adenocarcinoma of the stomach, colon, rectum, brochus, and breast. In some cases measurement of plasma trypsin may be of help in the differential diagnosis of steatorrhoea.