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.     

Impairment of humoral regulation of exocrine pancreatic function in chronic pancreatitis

AIM: To elicit the role of cholecistokinin (CCK), biogenic amines, bile acids (BA) in development of functional pancreatic insufficiency (PI) in chronic pancreatitis (CP). MATERIAL AND METHODS: Blood concentrations of CCK, serotonin and acetylcholin, fecal concentration of elastase (E-1), BA spectrum in the blood and duodenal content were studied in 46 CP patients (20 patients with alcoholic pancreatitis--AP and 26 patients with biliary pancreatitis--BP) and 15 healthy controls. RESULTS: In AP patients E-1 fell to 78.4 +/- 6.3 mcg/g (severe exocrine PI), while in BP patients E-1 was 170.0 +/- 28.9 mcg/g. CCK in AP and BP decreased to 0.33 +/- 0.03 and 0.45 +/- 0.03 ng/ml, respectively (control--1.60 +/- 0.02 ng/ml, respectively, p < 0.05). AP and BP patients had a rise in the absolute concentration and percentage of the total fraction of the taurodioxicholanic acids to 10.2 +/- 1.6 and 15.0 +/- 2.3%, respectively, (control 9.5 +/- 1.2%) in duodenal bile. The concentration of glycocholic acid fell to 24.1 +/- 1.6 and 23.7 +/- 3.7%, respectively, (control--36.4 +/- 2.4%, p < 0.05). AP patients had more significant decrease of taurocholic acid--to 4.5 +/- 0.7% (control--9.2 +/- 0.7%, p < 0.05). In the peripheral blood of AP patients there was an elevated basal level of serotonin and acetylcholine in the presence of low cholinesterase activity. After meal, acetylcholine concentration lowered in high secretion of serotonin. CONCLUSION: Depending on severity of destructive changes in the pancreas, AP and BP patients had different degree of exocrine insufficiency which may be secondary to the absence of acetylcholine rise in the blood after meal. Alterations in the composition of the conjugates of cholic and taurodioxicholanic BA lead to alterations of CCK blood concentration and, therefore, to changes in exocrine pancreatic secretion. Imbalance between serotonin and acetylcholine levels after meal evidences for defects in conventional regulatory interrelations. Decreased threshold of nociceptors activation in simultaneous enhancement of afferent nociceptive flows may entail pain syndrome in CP.     

Different behaviour of the N-terminal and C-terminal fragment of proatrial natriuretic factor in plasma of healthy subjects as well as of patients with cirrhosis

N-terminal (atrial natriuretic factor (ANF) 1-98) and C-terminal (ANF 99-126) fragments of proatrial natriuretic factor (NTA and CTA, respectively) were determined in plasma of healthy subjects adopting different postures and in patients with cirrhosis. Seven healthy subjects were investigated while seated and 30 min after assuming a horizontal position. NTA plasma concentrations increased in subjects in the horizontal position (from 734 +/- 250 (SE) fmol/ml to 902 +/- 227 fmol/ml; p less than 0.05). In contrast, CTA plasma concentrations remained unchanged (9.2 +/- 1.3 fmol/ml vs 8.9 +/- 1.6 fmol/ml). In 10 patients with cirrhosis of the liver, NTA concentrations were markedly (p less than 0.001) elevated compared to 11 healthy subjects (2334 +/- 291 fmol/ml vs 743 +/- 155 fmol/ml). However, there was no difference of CTA plasma levels between cirrhotic patients and healthy subjects (8.7 +/- 1.3 fmol/ml vs 8.2 +/- 0.9 fmol/ml). These data demonstrate changes of the plasma concentration of the N-terminal fragment of proatrial natriuretic factor by posture and in liver disease, in contrast to unchanged levels of the C-terminal fragment.     

Can plasma human pancreatic polypeptide be used to detect diseases of the exocrine pancreas?

Plasma concentrations of human pancreatic polypeptide (HPP) parallel exocrine pancreatic secretion in response to stimulation with cholecystokinin. We determined prospectively the relationships among fasting HPP level, integrated HPP response to infusion of cholecystokinin, and output of trypsin and also the sensitivity, specificity, and predictive values of the fasting HPP level in the diagnosis of exocrine pancreatic disease. Our study group consisted of 19 patients with acute pancreatitis, 17 with chronic pancreatitis, and 25 with ductal adenocarcinoma of the pancreas and 27 control subjects. In the control patients and those with chronic pancreatitis, significant correlations were detected between HPP level and output of trypsin (P less than 0.001) in response to infusion of cholecystokinin and between fasting HPP and integrated HPP levels (P less than 0.004); no correlation was detected between HPP level and steatorrhea. The sensitivity, specificity, and negative and positive predictive values of the fasting HPP level for detection of either chronic pancreatitis or pancreatic cancer were similar and approximated 0.88, 0.67, 0.88, and 0.66, respectively. The HPP concentration had no value in detecting acute pancreatitis. Because the fasting HPP level has a high degree of negative predictability and is simpler to measure than the integrated HPP level or the output of trypsin, it may be a useful test in patients suspected of having either chronic pancreatitis or pancreatic cancer. A fasting HPP level of 125 pg/ml or greater could be used to exclude chronic pancreatitis or pancreatic cancer, but the finding of a value of less than 125 pg/ml necessitates use of other diagnostic tests for reliable determination of the presence of these diseases.     

Copper, zinc and copper/zinc ratio in chronic pancreatitis and pancreatic cancer

Serum copper and zinc levels and their ratio were evaluated in 48 control subjects, 29 patients with pancreatic cancer, 46 with chronic pancreatitis and 32 with extra-pancreatic diseases, with the purpose of ascertaining modifications in chronic pancreatic disease. Hepatic involvement and age were also investigated as possible factors influencing results. Cu/Zn ratio was found to be significantly increased in pancreatic cancer (2.66 +/- 0.16, mean +/- SE) as compared to controls (1.39 +/- 0.06, p less than 0.001), chronic pancreatitis (1.82 +/- 0.09. p less than 0.001) and extra-pancreatic diseases (1.81 +/- 0.18, p less than 0.001), but without practical clinical value. Serum zinc levels appear to decrease with age, while copper and Cu/Zn ratio increase. However, covariance analysis demonstrated that age does not play an important role in influencing copper and Cu/Zn ratio. A decreased liver synthetic function, at least in part age-related, seems to be an additional factor in decreasing serum zinc values.     

Studies of glucose intolerance in cirrhosis of the liver

Patients with hepatic cirrhosis often have demonstrable glucose intolerance. We studied 21 patients with cirrhosis of the liver. Oral glucose tolerance tests (OGTT), intravenous arginine stimulation tests (IVAST), and intravenous insulin tolerance tests (IVITT) were performed, and timed blood samples were obtained for the assay of glucose immunoreactive insulin (IRI), C-peptide (C-P), and immunoreactive glucagon (IRG). The 125I-insulin binding to circulating monocytes was studied in some of the patients. All results were compared to those of similar studies performed on healthy controls. During OGTT significant glucose intolerance was demonstrable in the patients with cirrhosis (2 hr plasma glucose 198.8 +/- 14.3 mg/dl in cirrhosis and 116.4 +/- 4.2 in controls; p less than 0.001). Two-hour plasma IRI, C-P, and IRG were significantly higher in the cirrhotic patients than in controls (p less than 0.001; less than 0.001; less than 0.025). In response to IVAST, the patients with cirrhosis showed a greater first-phase insulin secretion and controls had a slightly better second-phase insulin release. Plasma IRG rose from a basal value of 446 pg/ml to 1100 in the patients with cirrhosis and from 171 pg/ml to 494 in controls. After intravenous insulin administration, there was only a 40% decline in plasma glucose concentration from basal values in the patients with cirrhosis whereas the controls showed a 60% decline, demonstrating that the patients with cirrhosis had significant insulin resistance. Moreover, the half-life of insulin was prolonged in the patients with cirrhosis (t 1/2 = 15.5 min in cirrhosis and 10.3 in controls; p less than 0.001); and the ratio of C-P to insulin during OGTT was also reduced, indicating that the patients with cirrhosis have reduced hepatic clearance of insulin. The specific binding of 125I-insulin to circulating monocytes was 2.7% in cirrhosis, 2% in obese controls, and 4% in lean controls. There was a significant negative correlation between the fasting plasma insulin values and the specific binding of insulin. In conclusion, patients with hepatic cirrhosis have significant glucose intolerance characterized by hyperinsulinemia, hyperglucagonemia, insulin resistance, and down-regulation of insulin receptors. Although hyperinsulinemia is probably caused by reduced hepatic clearance of insulin, hyperglucagonemia is primarily due to increased pancreatic secretion.     

Plasma immunoreactive gamma melanotropin in patients with idiopathic hyperaldosteronism, aldosterone-producing adenomas, and essential hypertension.

A non-ACTH aldosterone-stimulating factor(s) has been implicated in the pathogenesis of idiopathic hyperaldosteronism (IHA). Although this factor has not been fully characterized, some evidence suggests that it may be related to a pro-gamma-melanotropin (pro-gamma-MSH), derived from the NH2-terminal region of pro-opiomelanocortin. In the present study, plasma immunoreactive (IR-) gamma-MSH levels at 0800 h in patients with IHA were evaluated (90 +/- 17 fmol/ml; range: 13-173 fmol/ml) and found to be significantly higher (P less than 0.05) than those in subjects with aldosterone-producing adenomas (33 +/- 8 fmol/ml), essential hypertension (33 +/- 6 fmol/ml), and normotensive controls (19 +/- 2 fmol/ml). Seven of nine IHA subjects had circulating IR-gamma-MSH levels above the normal range (greater than 35 fmol/ml). In plasmas sampled at 1200 h, IR-gamma-MSH was significantly higher in patients with IHA (95 +/- 26 fmol/ml) and adenomas (63 +/- 23 fmol/ml), as compared with essential hypertensives (31 +/- 6 fmol/ml) and normotensives (19 +/- 3 fmol/ml). Mean plasma IR-ACTH, plasma cortisol, and urinary cortisol levels did not differ significantly between any of these groups. In order to evaluate the effect of a pro-gamma-MSH in vitro, adrenal adenoma tissue was obtained from two patients, one with elevated IR-gamma-MSH (61 fmol/ml) and a second with low IR-gamma-MSH (12 fmol/ml). Aldosterone secretion by dispersed adenoma cells from the former, but not the latter, underwent a fourfold dose-dependent (10(-14)-10(-9) M) increase in response to human Lys-gamma 3-MSH. These data suggest that a pro-gamma-MSH may be implicated as a pathogenic factor in a subset of patients with primary aldosteronism, particularly among those differentially diagnosed as having IHA.     

Simultaneous Assay of Immunoreactive β-Lipotropin, γ-Lipotropin, and β-Endorphin in Plasma of Normal Human Subjects, Patients with ACTH/Lipotropin Hypersecretory Syndromes, and Patients undergoing Chronic Hemodialysis

We have studied the relative concentrations of the human immunoreactive (IR) peptides gamma-lipotropin (hgammaLPH, [1-58]hbetaLPH), beta-lipotropin (hbetaLPH), and beta-endorphin (hbetaEND, [61-91]hbetaLPH) using gel exclusion chromatography together with a specific radio-immunoassay (RIA) for hgammaLPH and a RIA that (because hbetaEND is the COOH-terminus of the hbetaLPH molecule) measures both hbetaEND and hbetaLPH on an equimolar basis. In normal subjects, basal plasma IR-hgammaLPH was often undetectable (<12.5 fmol/ml), but ranged up to 21 fmol/ml, and IR-hbetaEND/hbetaLPH was 10.8+/-0.7 fmol/ml; previous studies by others suggest that most of the IR-hbetaEND/hbetaLPH was probably hbetaLPH. Both IR-hgammaLPH and IR-hbetaEND/hbetaLPH were significantly elevated (P < 0.001) in patients undergoing chronic hemodialysis (101.5+/-12.7 and 23.8+/-2.0 fmol/ml, respectively). Their IR-hgammaLPH coeluted with standard hgammaLPH as a single peak, and IR-hbetaEND/hbetaLPH coeluted with hbetaLPH; no distinct peak of IR-hbetaEND was observed. In patients with ACTH/LPH hypersecretion due to Addison's disease, Nelson's syndrome, or ectopic ACTH syndrome, IR-hgammaLPH and IR-hbetaEND/hbetaLPH were both elevated, and IR-hbetaEND/hbetaLPH eluted as two peaks, one coeluting with hbetaLPH and the other with hbetaEND. The molar concentrations of all three peptides were significantly correlated with one another. The lower concentrations of endogenous IR-hbetaEND observed may be due in part to its apparent shorter plasma half-life, as estimated in an Addison's patient given a cortisol infusion. The biologic significance of these three peptides in circulating blood is still unknown. The increased levels of hbetaLPH and hgammaLPH in plasma of patients with chronic renal failure suggest that the kidney may be an important organ for their metabolism.     

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.     

Substance P, acetylcholinesterase, and beta-endorphin levels in the plasma and pericardial fluid of patients with and without angina pectoris.

We measured substance P-like immunoreactivity (SPLI), beta-endorphin-like immunoreactivity (BELI), acetylcholinesterase activity, and total protein content in pericardial fluid and plasma of patients with angina pectoris and patients with no angina pectoris. SPLI and BELI levels, acetylcholinesterase activity, and total protein content were determined by radioimmunoassay, a colorimetric method, and by the method of Lowry et al. (J Biol Chem 1951; 193:265-75), respectively. In the pericardial fluid, patients with angina had SPLI, BELI, acetylcholinesterase, and total protein values of 1.69 +/- 0.23 fmol/mg protein, 0.16 +/- 0.13 fmol/mg protein, 0.06 +/- 0.02 units, and 25.7 +/- 3.2 mg/ml, respectively. Patients with no angina had SPLI, BELI, acetylcholinesterase, and total protein values of 0.93 +/- 0.17 fmol/mg protein, 0.19 +/- 0.10 fmol/mg protein, 0.16 +/- 0.02 units, and 44.6 +/- 5.3 mg/ml, respectively. SPLI levels were significantly higher (p less than 0.03), and acetylcholinesterase (less than 0.002) and total protein content (less than 0.004) were significantly lower in the pericardial fluid of patients with angina when compared with those of patients with no angina. BELI levels were not significantly different between the two groups. In the plasma, no significant differences were found in SPLI, BELI, acetylcholinesterase, and total protein values between the two groups of patients. Patients with angina had SPLI, BELI, acetylcholinesterase, and total protein values of 0.47 +/- 0.26 fmol/mg protein, 0.06 +/- 0.06 fmol/mg protein, 0.29 +/- 0.15 units, and 68.2 +/- 8.7 mg/ml, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

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.     

Hyperlipidemia in renal failure: studies of plasma lipoproteins, hepatic triglyceride production, and tissue lipoprotein lipase in a chronically uremic rat moedl.

To determine whether hypertriglyceridemia in chronic renal failure resulted from altered production and/or removal, Sprague-Dawley rats in which chronic uremia had been induced by five-sixths nephrectomy were studied. In this model, basal plasma TG levels were higher than in controls (uremic 141 +/- 52 mg/100 ml; control 83 +/- 25; mean +/- SD; p less than 0.001) at 1 month after nephrectomy and remained significantly elevated throughout the 10-week duration of study. In the uremic animals hepatic TGSR's (Triton) were not increased (uremic 0.56 +/- 0.11 mg/min; control 0.63 +/- 0.13) and AcCoAc, the rate-limiting enzyme in hepatic lipogenesis, was significantly reduced (control 24.5 +/- 3.8 nM/min/mg protein; uremic 18.2 +/- 1.1; p less than 0.005). The TG removal system--heparin-elutable LPL activities--was similar in control and uremic animals in heart, diaphragm, and adipose tissue. However, serum from both acute and chronically uremic rats lowered adipose LPL activity (P less than 0.01). These observations suggest that in uremia (1) TG production is not increased and (2) the clearance of TG-rich lipoprotein from the circulation is reduced because of a functional impairment in LPL.     

Plasma bone Gla protein concentrations in healthy adults. Dependence on sex, age, and glomerular filtration

Plasma bone Gla protein (BGP) was determined by radio-immunoassay in 266 healthy adults, men (n = 132) and women (n = 134), aged 20-79 years. In the women aged 30-69 years, plasma BGP increased significantly with age (r = 0.44, p less than 0.001), and a particularly steep increase was seen from 1.1 +/- 0.5 (mean +/- 1 SD) in the fifth decade to 2.0 +/- 1.4 nmol/l in the seventh decade. In men, aged 30-69 years, no correlation was found between plasma BGP and age (r = -0.07, NS). Plasma bone Gla protein is removed from the circulation mainly by the kidneys and the increased plasma BGP in the women could be caused by decreased renal clearance. The interrelationship was analysed by means of partial correlation. When creatinine clearance was held constant in women, BGP still correlated positively with age (r = 0.40, p less than 0.001), but not with creatinine clearance (r = 0.003, NS) when age was fixed. Plasma BGP was significantly increased above normal in 35 patients with chronic renal failure (10.2 +/- 14.6 nmol/l). Non-linear regression analysis showed that plasma BGP was within the normal range when 24-h creatinine clearance was greater than 30 ml/min, and large increases in plasma BGP did not occur until the 24-h creatinine clearance was below 20 ml/min. We conclude that, in normal subjects and patients with mild to moderate renal failure, plasma elevations of BGP reflect increased bone turnover rather than decreased renal clearance.     

Fasting serum cholecystokinin immunoreactivity in chronic relapsing pancreatitis

Summary An increase in fasting cholecystokinia (CCK) levels has been reported in patients with pancreatic insufficiency, but the relationship of these findings to the clinical conditions has not been established. We, therefore, measured fasting serum CCK-like immunoreactivity in 70 patients with chronic relapsing pancreatitis (CRP) (38 non-surgically treated and 32 previously surgically treated) and in 44 healthy subjects. The radioimmunoassay detected three circulating forms of CCK. The mean value of the CCK levels in CRP (260.3±300.8 pg/ml) was significantly higher than that of the controls (56.6±61.7 pg/ml) (p<0.001), but in 39 (56.7%) of the 70 CRP cases the CCK was in the normal range. A smaller overlap with the controls was observed in the non-surgically than in the surgically treated patients (45 vs. 71.8%). In the 38 non-surgically treated CRP cases no relationship was observed between the CCK levels and each of the following parameters: age, length of history, presence or absence of pancreatic calcification, nutritional and alcoholic habits, and the results of exocrine function tests. The absence of the last-mentioned correlation is some-what unexpected if the high CCK levels are due to the interruption of a feedback loop for CCK secretion. However, previous pancreatic surgical drainage and/or treatment with pancreatic enzymes, present in almost all these patients, could have an effect on CCK behaviour. An abstract of this paper was presented at the 10th Meeting of the European Pancreatic Club, Dublin, October 1977. This research was supported in part by a grant from theConsiglio Nazionale delle Ricerche (CNR), Roma, Italy, grant CT 77.01498.04.     

High-performance liquid chromatographic characterization of neurophysins in chronic renal failure

Levels of immunoreactive (IR) oxytocin (OT)-associated or estrogen-stimulated neurophysin (ESN) and vasopressin-associated or nicotine-stimulated neurophysin (NSN) were measured in plasma of patients with chronic renal failure before and after hemodialysis (HD) and intermittent peritoneal dialysis (IPD), and during continuous ambulatory peritoneal dialysis (CAPD). ESN-IR in 17 patients before HD was 24.4 +/- 2.7 ng/ml (mean +/- SEM) and increased after HD to 33.2 +/- 4.1 ng/ml (P less than 0.001). ESN-IR in 17 patients with CAPD was 15.2 +/- 3.4 ng/ml, significantly lower than in patients undergoing HD, P less than 0.001. In patients receiving IPD (n = 6), ESN was 11.6 +/- 3.7 ng/ml and did not change significantly after IPD. Levels of ESN in patients with renal failure were increased compared with levels in normal individuals, 1.0 +/- 0.1 ng/ml. Levels of ESN were not correlated with laboratory parameters that may be abnormal in renal failure. NSN levels in 16 of 17 patients undergoing HD were 3.2 +/- 0.34 ng/ml and in 14 of 17 patients with CAPD were 2.9 +/- 0.4 ng/ml, respectively. ESN before HD (r = 0.63, P less than 0.01), after HD (r = 0.85, P less than 0.001), and in patients with CAPD (r = 0.83, P less than 0.001) and IPD (r = 0.81, P less than 0.05) correlated significantly with an OT-like peptide previously found to be increased in renal failure.(ABSTRACT TRUNCATED AT 250 WORDS)     

Accelerated in vitro degradation of CCK-58 in blood and plasma of patients with acute pancreatitis

Proteases released into the circulation during acute pancreatitis may hydrolyse circulating peptide hormones leading to altered regulatory functions. Cholecystokinin is a major regulator of postprandial gut function; stimulating pancreatic enzyme secretion, gallbladder contraction and diminishing food intake. Cholecystokinin-58 is the largest and most abundant form of this hormone in acid extracts of human intestine, and major amounts are released into the circulation after feeding. In order to test whether cholecystokinin-58 is degraded more rapidly due to the increased circulating of enzymes, this peptide was added to blood and plasma of patients with acute pancreatitis and incubated for various time intervals. The in vitro half life of cholecystokinin-58 was 10 +/- 1 minutes (mean +/- SE) in plasma and 11 +/- 1 min in blood from patients with acute pancreatitis, about four fold lower than the half life in plasma of healthy volunteers; 45 +/- 5 min. Degradation of cholecystokinin-58 produced immunoreactive forms of cholecystokinin that eluted in the positions of cholecystokinin-8 and cholecystokinin-33/39. We conclude that acute pancreatitis increases the degradation of CCK molecules.     

The BT-PABA/PAS test in tropical diabetes.

A 'screening' test is needed to identify patients with chronic pancreatitis among diabetics in tropical field surveys. We have examined the potential diagnostic yield of the BT-PABA/PAS test of exocrine pancreatic function in this setting. The recoveries of both PABA and PAS in eight healthy controls from Madras, south India, were lower than in controls from Manchester, north west England (mean +/- S.D., 51 +/- 11 vs. 79 +/- 7%, P < 0.001 for PABA; 52 +/- 11% vs. 81 +/- 7%, P < 0.001 for PAS) but the % PABA/PAS excretion index (PEI) was similar (0.96 +/- 0.14 vs. 0.96 +/- 0.06). Using a cut-off value of 0.75 for the PEI in a study group including eight patients with chronic pancreatitis and 26 with primary forms of diabetes, test sensitivity was 75%, specificity 92%, positive predictive value 75%, negative predictive value 92% and efficiency 88%.     

Effect of somatostatin on metabolic changes following ERCP

An investigation was carried out on the ameliorating effect of cyclic somatostatin on the biochemical changes and impairment of glucose tolerance which follow endoscopic retrograde pancreatography. Serum amylase and plasma insulin and glucagon levels were significantly lower in a group of 20 patients receiving somatostatin prior to pancreatic radiography than in 35 control patients without such pretreatment. (Maximum increases in control and somatostatin-pretreated patients, respectively were: amylase: 4695 +/- 290; 1037 +/- 155 U/l p less than 0.001; insulin: 504 +/- 89; 179 +/- 43 pmol/l p less than 0.001; glucagon: 394 +/- 44; 62 +/- 13 pmol/l p less than 0.05.) Impairment of glucose tolerance was also considerably less in the patients given prophylactic somatostatin. These results indicate that postpancreatographic metabolic abnormalities can be ameliorated, or possibly even prevented altogether, by prior administration of somatostatin.     

Atrial natriuretic factor in chronic obstructive lung disease with pulmonary hypertension. Physiological correlates and response to peptide infusion.

To investigate the physiological role of atrial natriuretic factor (ANF) in patients with hypoxic pulmonary hypertension secondary to chronic obstructive lung disease (COLD), we infused synthetic alpha-human ANF in seven such patients, and investigated the physiological correlates to circulating peptide levels in 24 patients with COLD. ANF infusion, at incremental rates of 0.01, 0.03, and 0.1 micrograms/kg.min, increased basal plasma immunoreactive (ir) ANF (136 +/- 38 pg/ml) by 3-, 10-, and 26-fold, respectively, and reduced pulmonary artery pressure (from 33 +/- 3 to 25 +/- 2 mmHg, P less than 0.001) and systemic arterial pressure (from 88 +/- 4 to 79 +/- 4 mmHg, P less than 0.001) in a dose-related fashion. Cardiac index increased by 13.5% (P less than 0.01) while heart rate was unchanged. Cardiac filling pressures decreased at 0.1 micrograms/kg.min ANF. Pulmonary and systemic vascular resistance fell by 37% (P less than 0.001) and 19% (P less than 0.001), respectively. Arterial oxygenation was impaired during ANF infusion, suggesting partial reversal of hypoxic pulmonary vasoconstriction. Plasma renin activity remained unchanged but aldosterone fell by 44% (P less than 0.01). The levels of plasma irANF in 24 patients correlated directly with the degree of hemoconcentration (r = 0.67, P less than 0.001), respiratory acidosis (r = -0.65, P less than 0.001), and pulmonary hypertension (r = 0.52, P less than 0.01). The results suggest that ANF may serve as a potent pulmonary vasodilator involved in the circulatory homeostasis of patients with COLD.     

Discrepancies between the Doses of Cholecystokinin or Caerulein-Stimulating Exocrine and Endocrine Responses in Perfused Isolated Rat Pancreas

The effects of highly purified natural porcine cholecystokinin (CCK) and synthetic caerulein on the rate of flow of pancreatic juice, the rate of output of amylase, and the rate of release of immunoreactive insulin (IRI) and immunoreactive glucagon (IRG) were simultaneously investigated in the isolated perfused rat pancreas.The maximal flow rate of pancreatic juice was obtained with concentrations of CCK ranging from 0.5 to 10 mU/ml, whereas amylase output was maximal at CCK concentrations from 1 to 10 mU/ml. Caerulein at concentrations of 0.05-1 ng/ml induced a similar maximal flow rate and amylase secretion. Supramaximal stimulatory concentrations of these peptides resulted in lower rates of release of fluid and amylase than with the maximally effective concentrations. Stimulation of IRI and IRG release was elicited only with concentrations of peptides supramaximal for effects on the exocrine responses.The demonstration of very similar discrepancies between the doses of caerulein required to elicit maximal exocrine responses and those required to elicit endocrine responses provide strong evidence that the pattern of the effect of the porcine CCK is accounted for by CCK itself.Although caerulein had no influence on IRI response when superimposed on 100 or 150 mg/100 ml glucose stimulation, preperfusion of caerulein led to a significant enhancement of IRI response to a subsequent glucose stimulation in both phases. The augmentation effect was completely separate from the direct IRI-stimulating effect of caerulein, because the CCK-like peptide requires no glucose for insulinotropic action.Because the concentrations of the peptides necessary for stimulation of endocrine responses were inhibitory in their effects on exocrine responses, it may be inferred that it is unlikely that the endocrine effect is physiologically important, though the results of caerulein for augmenting glucose-stimulated IRI release suggests a possible role for CCK in carbohydrate metabolism.