Alpha 1-antitrypsin deficiency and liver disease.
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Humans↗
Biomedical subjects
G Lake-Bakaar
Publications and source records attributed to G Lake-Bakaar.
Origin of circulating serum immunoreactive trypsin in man.
Serum trypsin concentrations within the portal venous system have been measured in man during transhepatic portal venography in an attempt to determine its source. In eight experiments, mean serum trypsin concentration at the splenic hilum was 180 +/- 25 ng/ml (mean +/- SEM). Trypsin concentration in the rest of the splenic vein was not significantly different. The mean concentrations in the portal vein (210 +/- 32 ng/ml) and within the superior mesenteric vein (233 +/-- 29 ng/ml) were, however, significantly higher than at the hilum (P less than 0.05). Following cholecystokinin-pancreozymin (CCK-PZ) and secretin stimulation, marked increases in serum trypsin concentration were seen within the portal vein (two patients) and deep within the superior mesenteric (two out of three patients). We conclude that circulating serum trypsin is derived, at least in part, from intestinal reabsorption.
Adult↗
The effects of bile salts on the radioimmunoassay of hormonal peptides.
The effect of bile salts on RIAs of secretin, glucagon, insulin, and gastrin have been studied. Increasing concentrations of the sodium salts of taurocholic, glycochenodeoxycholic, taurochenodeoxycholic, glycocholic, and taurodeoxycholic acids progressively inhibit the binding of 125I-secretin to specific antibody, resulting in significant lowering of the B/F ratio at concentrations as low as 0.04 mM and almost complete inhibition at concentrations above 2.4 mM. The nonspecific inhibition by taurodeoxycholate results in a B/F vs. concentration curve resembling a secretion standard curve. The binding of 125I-secretin to charcoal is also inhibited by increasing concentrations of bile salts, although this effect is less marked than their effects on the immune reaction. The binding of 125I-glucagon, 125I-insulin, and 125I-gastrin to specific antisera is also inhibited by sodium taurocholate. Insulin binding is least affected. However, gastrin binding is inhibited by sodium taurocholate at a concentration as low as 0.2. The binding of 125I-insulin and 125I-gastrin to charcoal is also inhibited by sodium taurocholate. Thus bile salts interfere in the RIA of hormonal peptides by inhibiting both the immune reaction and the binding of labeled antigen to charcoal. These nonspecific effects must therefore be considered in RIA of body fluids containing high concentrations of bile salts. Treatment of plasma samples with anionic-binding resins can eliminate interference caused by high bile salt concentrations. However, these resins will also remove anionic hormonal peptides such as gastrin.
Bile Acids and Salts↗
The pancreas in primary biliary cirrhosis and primary sclerosing cholangitis.
In patients with primary biliary cirrhosis, the chronic cholestasis, salivary, and lacrimal hyposecretion suggest that the disease is a "dry gland" syndrome. To determine whether or not pancreatic damage occurs in primary biliary cirrhosis and other forms of chronic cholestasis, we have studied pancreatic structure and function in primary biliary cirrhosis, and primary sclerosing cholangitis. In a retrospective study, retrograde pancreatograms were abnormal in 43% of 35 patients with primary biliary cirrhosis and 15% of 20 patients with primary sclerosing cholangitis (p less than 0.02). In a prospective study, serum pancreatic isoamylase was abnormal in 56% of 41 patients with primary biliary cirrhosis and 36% of 22 patients with primary sclerosing cholangitis (NS), indicating pancreatic damage in both diseases. After secretin-pancreozymin stimulation, patients with primary biliary cirrhosis, but not patients with primary sclerosing cholangitis, showed a significant reduction in duodenal juice flow rate (p less than 0.01) and immunoreactive trypsin output (p less than 0.01). The reduced trypsin output in patients with primary biliary cirrhosis indicates pancreatic hyposecretion. In neither patients with primary biliary cirrhosis nor patients with primary sclerosing cholangitis was the immunoreactive trypsin concentration, or tryptic activity in duodenal juice, significantly different from controls. Pancreatic involvement in primary biliary cirrhosis is closely associated with Sjogrens syndrome, and it is likely that the pancreatic hyposecretion is a component of the sicca complex. This association was not obvious in primary sclerosing cholangitis.
Cholangitis↗
Recovery of secretin in acid small intestinal lumen perfusates in the rabbit.
Immunoreactive secretin concentrations were measured in femoral venous plasma and in intestinal perfusates during acid and neutral perfusion of small intestinal segments in anesthetized rabbits. Steady-state plasma and luminal secretin concentrations were less than 20 pg/ml. Duodenal perfusion with with 0.1 N hydrochloric acid stimulated peak plasma immunoreactive secretin concentrations of 200 - 300 pg/ml within five minutes. Acid stimulated plasma concentrations remained constant during 30 minutes of perfusion. Secretin output into the acid perfusate (2000 - 4000 pg/min) accompanied the release into plasma. Subsequent perfusion with a neutral solution resulted in a rapid return to steady-state plasma and luminal secretin concentrations. Sequential acid perfusion of the ileum, jejunum, and duodenum stimulated similar concentrations of secretin in plasma and luminal perfusates.
Animals↗
Pancreatic hypofunction in extrahepatic portal venous obstruction.
Pancreatic function was studied in 29 patients with extrahepatic portal venous obstruction, and 30 age-matched controls. The aetiology of the portal venous obstruction was known in 20 out of 29 patients. No patient had a history of pancreatitis. Serum trypsin, both fasting and for 120 minutes after a Lundh meal, was significantly lower in the patients than in controls (P less than 0.005). 5/28 (18%) patients had reduced fasting serum trypsin levels and in 5/14 trypsin was abnormal after a Lundh meal. Mean fasting serum glucose (3.8 +/- ).49 mmol/l was significantly higher than in control subjects (mean 3.4 +/- 0.42 mmol/l) (P less than 0.05). After 100 g glucose orally, mean serum glucose at 180 minutes (5.26 +/- 1.58 mmol/l) was higher than the control value (3.96 +/- 1.45 mmol/l) (P less than 0.05), and 30 and 60 minutes serum C-peptide values were significantly lower (P less than 0.005). Pancreatic hypofunction found in these patients probably results from an abnormal portal circulation in association with mild pancreatic damage secondary to chronic venous congestion.
Adolescent↗
Measurement of trypsin in duodenal juice by radioimmunoassay.
Trypsin in duodenal aspirate and pure pancreatic juice samples has been measured by both radioimmunoassay and enzymatic mathods. The radioimmunossay has been shown to be specific and to detect trypsin in the presence of aprotinin (Trasylol). In duodenal juice samples from control subjects and from patients with primary biliary cirrhosis a good correlation was obtained between both immunoreactive trypsin concentration and trypsin activity. The immunoreactive trypsinogen concentration in pure pancreatic juice also correlated well with activated trypsin activity. The mean immunoreactive trypsin concentration and the concentration of enzymatically inert immunoreactive trypsin in duodenal juice samples from patients with primary biliary cirrhosis were significantly lower than controls, suggesting pancreatic hyposecretion in this disease. After five duodenal juice samples had been stored for three months at -70 degrees C, immunoreactive trypsin concentration in samples stored without Trasylol were reduced by 12 . 0 +/- 4 . 2 (mean +/- SD) times the concentration of samples stored in Trasylol. Trypsin autodegradation continues even at -70 degrees C; Trasylol protects against this. Radioimmunoassay is a reliable method of trypsin estimation in duodenal juice and has advantages over conventional enzymatic analysis.
Adult↗
Metabolism of 125I-labelled trypsin in man: evidence of recirculation.
125I-labelled human trypsin metabolism has been investigated in man. Three subjects received 125I-trypsin and 131I-albumin intravenously. Against a background secretin infusion (1 U/kg/h), trypsin decayed biexponentially from the serum with half-lives of 17.5, 21, and 24 minutes for the rapid disappearance phase and 520, 540, and 560 minutes for the slow phase. Between 13% and 38% of the 125I injected was recovered from duodenal juice aspirated continously over 300 minutes. In contrast, less than 1% of the 131I-albumin injected was recovered. When bile and pure pancreatic juice were collected at endoscopic retrograde cholangiopancreatography after intravenous 125I-trypsin in a fourth subject 125I radioactivity was found to be secreted via both these routes. After 125I-trypsin infusion into the duodenum 11% of the total dose was found to be present in the circulation after 75 minutes. These results support the concept that recirculation of trypsin exists in man.
Adult↗
The relative values of serum immuno-reactive trypsin concentration and total amylase activity in the diagnosis of mumps, chronic renal failure, and pancreatic disease.
Fasting serum concentrations of trypsin and amylase activity have been compared in 107 subjects, including 18 controls and patients with mumps, acute pancreatitis, chronic pancreatitis, cancer of the pancreas, and chronic renal failure. There was no significant correlation between amylase activity and trypsin concentrations in any of these groups. In all 12 patients with acute pancreatitis and all 16 with chronic renal failure the serum immuno-reactive trypsin concentrations were elevated. Amylase activity was increased in 87% (20 out of 23) of patients with mumps, but only 13% (3 out of 23) had hypertrypsinaemia suggesting subclinical pancreatitis. In 18 patients with chronic pancreatitis low levels of serum trypsin were measured in 11 (61%), reflecting a decrease in pancreatic acinar mass. In contrast, serum amylase was normal or raised in all 18. Subnormal values of the trypsin to amylase ratio was obtained in 15 (83%). Trypsin levels in 20 patients with carcinoma of the pancreas were abnormal in 11 (55%). Six (30%) had abnormal amylase levels. It is concluded that it is more useful to measure the serum trypsin concentration than the amylase activity in the diagnosis of both mumps-pancreatitis and chronic pancreatic disease and that the trypsin to amylase ratio is more sensitive than either enzyme alone in the diagnosis of chronic pancreatitis.
Adult↗
The decay of endogenously labelled 75Se-selenomethionine labelled proteins in duodenal juice: evidence for recirculation in man.
The decay of the specific radioactivity of duodenal juice proteins, endogenously labelled with 75Se-selenomethionine has been studied in man. Duodenal juice was collected against a background infusion of cholecystokinin-pancreozymin (1 unit/kg/hr) and secretin (1 unit/Kg/hr). In 4 subjects, duodenal juice was aspirated continuously and pooled in 30 min. aliquots. In 3 other subjects approximately 5-10 ml of juice was removed at 15 min, intervals. The rate of decay of protein specific radioactivity was significantly more rapid in the drainage group (p less than 0.01). A similar trend was also observed for trypsin. The data suggests that endogenous duodenal juice proteins might be recirculated as intact proteins in man.
Adult↗
Urinary immunoreactive trypsin excretion: a non-invasive screening test for pancreatic cancer.
The ratio of renal clearance of immunoreactive trypsin relative to renal clearance of creatinine was measured in 71 subjects including 27 controls and patients with cancer of pancreas, chronic pancreatitis, and acute pancreatitis. The upper limit of the control range was 4.1 x 10(-5) (mean + 2SD). 6 of 9 patients (67%) with acute pancreatitis had raised values. All 18 patients with chronic pancreatitis had values within the control range. In contrast, all 17 patients with carcinoma of pancreas had raised clearance ratios. The test may therefore prove valuable in distinguishing between chronic pancreatitis and cancer of pancreas.
Acute Disease↗
Serum immunoreactive trypsin concentration after a Lundh meal. Its value in the diagnosis of pancreatic disease.
The changes in serum trypsin concentration have been measured in 47 subjects for up to 2 hours after a Lundh meal. In 18 healthy controls, mean fasting trypsin concentration was 285 +/- 125 ng/ml (mean +/- 2 SD). The maximum increase after the Lundh meal (the trypsin response ratio) was 6.7 +/- 7.5%. Six patients with chronic renal failure had elevated fasting serum trypsin concentrations (range 460-1100 ng/ml) but trypsin response ratios fell within the control range. Of five patients with relapsing pancreatitis, two had raised and three normal or low fasting trypsins. After stimulation two had elevated trypsin response ratios; one of the two had evidence of main duct obstruction. Eleven out of 12 patients with chronic pancreatitis (with or without insufficiency) had low fasting trypsin concentrations (range 0-120 ng/ml) Seven of the 12 also had raised trypsin response ratios. In six patients with cancer of the pancreas, fasting trypsin was low in three, normal in two, and raised in one. Both patients with a normal fasting level had a raised trypsin response ratio. The combination of a single estimation of fasting serum trypsin concentration followed by serial measurements after a Lundh meal provides a useful screening test for chronic pancreatic disease.
Chronic Disease↗
Polyarteritis nodosa presenting with bilateral nerve deafness.
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Audiometry↗