[The diagnostic validity of non-invasive pancreatic function tests--a meta-analysis]. / Die diagnostische Validität nichtinvasiver Pankreasfunktionstests -- Eine Metaanalyse.

BACKGROUND: The paper discusses the non-invasive (tubeless) pancreatic function tests used to diagnose exocrine pancreatic insufficiency (EI). Studies evaluating the diagnostic validity of these tests are integrated into a meta-analysis, provided that they comply with the following criteria: The sensitivity (Ss) of a test has to be calculated by comparing it with an invasive function test which is accepted as the gold standard of pancreatic function diagnostics. Furthermore, the test must differentiate between slight (sl), moderate (md) and severe (sv) EI. For assessment of the specificity (Sp), the control group should not contain healthy persons but rather patients with other gastrointestinal diseases and a normal pancreatic function. In the statistical evaluation, each study was weighted according to the number of persons included. RESULTS: Tests (n = sum of persons included in all analysed studies): Fecal chymotrypsin: Ss (n = 169) 54 % (sl EI), 53 % (md EI), 89 % (sv EI), Sp (n = 202) 74 %. NBT-PABA test: Ss (n = 394) 49 % (sl EI), 64 % (md EI), 72 % (sv EI), Sp (n = 218) 83 %. Pancreolauryl test: Ss (n = 320) 63 % (sl EI), 76 % (md EI), 94 % (sv EI), Sp (n = 171) 85 %. Fecal elastase-1: Ss (n = 307) 54 % (sl EI), 75 % (md EI), 95 % (sv EI), Sp (n = 347) 79 %. Additional tests discussed but not included in the meta-analysis were fecal fat, (13)C breath tests, amino acid consumption test, serum tests. CONCLUSION: None of the non-invasive pancreatic function tests is sensitive enough to diagnose reliably a slight to moderate exocrine pancreatic insufficiency.

Inositol 1,4,5-trisphosphate formation, cytoplasmic calcium dynamics, and alpha-amylase secretion of pancreatic acini isolated from aged and chronically alcohol-fed rats.

METHODS: Three-month-old female Wistar rats were fed with 20% alcohol in their drinking fluid over 6-17 mo using an interrupted feeding regimen. At different times, pancreatic acini were isolated by mild collagenase digestion. The concentrations of inositol-1,4,5-trisphosphate (1,4,5-IP3) were determined by a specific radioreceptor assay, before and at different times after stimulation with varying concentrations of CCK-8. CCK-induced dynamics of cytoplasmic calcium ([Ca2+]c) was investigated in acinar cells by confocal laser raster microscopy. Acinar alpha-amylase (Aml) secretion was measured as enzyme activity in the medium compared to the total activity in the suspension. RESULTS: In 12-13-mo-old rats, the CCK-stimulated 1,4,5-IP3 formation in acini was found to be decreased compared to young rats (age 4 mo). In rats of the same age fed with ethanol from the age of 3 mo on, 1,4,5-IP3 concentrations in acini were higher and reached values comparable to those in young rats. Correspondingly, the CCK-induced [Ca2+]c dynamics in acini isolated from 9-mo-old rats was impaired compared to that of young rats but normal in aged, chronically alcohol-fed rats. Aml secretion under CCK stimulation, however, which was decreased in aged rats, was additionally impaired after alcohol feeding. CONCLUSION: Chronic alcohol feeding modifies 1,4,5-IP3 formation, the [Ca2+]c dynamics of, and the Aml secretion of rat pancreatic acini in response to CCK stimulation. Obviously, the age-related impairment of 1,4,5-IP3 formation and [Ca2+]c dynamics is improved. In contrast, the decrease in Aml secretion of acini isolated from aged rats is more pronounced after long-term alcohol-feeding.

Different dosages of acetylsalicylic acid lead to adverse modifications of the reaction of rat pancreas to ethanol.

CONCLUSION: Acetylsalicylic acid (aspirin, ASA) in a therapeutic dose prevents lipid peroxidation and damage of cell organelles in pancreatic tissue of rats chronically fed with ethanol. In contrast, higher ASA dosages lead to enhanced biochemical and morphological signs of pancreatic damage different from findings in rats fed by ethanol alone. METHODS: Two groups of rats received 20% alcohol as drinking fluid plus a diet containing either 6 (S6) or 10 g/kg (S10) ASA. Two control groups received no ASA (CA) and neither ASA nor alcohol (CW), respectively. Feeding was performed by the interrupted feeding regimen with four 18-h periods of food and fluid withdrawal weekly. After 7 mo, pancreatic tissue was examined by light and electron microscopy. In pancreas homogenates, the contents of malondialdehyde (MDA), protein, trypsinogen, lipase, pancreatic secretory trypsin inhibitor, acid phosphatase (AcPh), cathepsin B, beta-glucuronidase, and desoxyribonucleic acid were determined. RESULTS: In the pancreas of group CA, we found a 100% increase of MDA compared with group CW, increased fat deposition, as well as damaged mitochondria (Mito) and endoplasmic reticula (ER) in acinar cells, decreased protein content, decreased AcPh activity, and unchanged secretory parameters. The ASA-fed groups showed MDA contents indistinguishable from group CW. Protein and secretory parameters were decreased. Lysosomal enzymes were decreased in S6, but in S10, they were always higher than in group S6 and mostly as high as in group CW. Fat deposits were as frequent as in group CA. Mito and ER were mostly well preserved, but more autophagosomes and residual bodies occurred, particularly in group S10.

Anomalous pancreatico-biliary junction--report of a new experimental model and review of the literature.

A model of anomalous pancreatico-biliary junction was developed and used to investigate a possible role in the development of choledochal cyst and tumors of the biliary tract. An anastomosis was constructed between an isolated pancreas-duodenal segment and the gallbladder in 20 minipigs, but the results did not show any subsequent dilatation of the biliary tract, although intestinal metaplasia was observed in 20% of the animals. The severity of the epithelial changes was proportional to the duration of the experiment and may represent a premalignant change. A critical review of all reported animal models of anomalous pancreaticobiliary junction also is provided.

[Modification of alcohol-induced pancreatic damage in rats by soybean diet]. / Beeinflussung der alkoholinduzierten Pankreatopathie bei Ratten durch Sojabohnendiät.

Alcohol-induced hypersecretion probably contributes to chronic alcoholic pancreatitis. Feeding of raw soybean flour or soybean trypsin inhibitor also stimulates protein secretion of the pancreas. Therefore, we tested whether or not the pancreatic damage is increased by additional feeding of raw soybean flour in rats fed 20% ethanol. After 11 months, we classified the morphological lesions of the pancreas into seven stages of severity calculated by means of a discriminating procedure. In order to characterize the secretory capacity of the pancreas, we measured the outputs of lipase, phospholipase, A, alpha-amylase, carboxypeptidase A, chymotrypsin, and bicarbonate. Compared with the alcohol-fed animals, the rats fed with alcohol and soya exhibited a lower average degree of morphological damage in the pancreas. Hypertrophy and hyperplasia of the parenchyma and accumulation of secretory products within the acinar cells were main features. On the other hand, some separate regions of the pancreas showed intraductal secretion precipitates as well as plugs, which were sometimes associated with atrophy of acinar cells. Feeding with soybean diet grossly reduced the alcohol-induced enzyme hypersecretion. In the early phase of alcohol-induced pancreatic damage, long-term soybean flour diet thus reduces morphological lesions and hypersecretion of the rat pancreas, whereas protein synthesis in the acinar cells appears increased. However, the precipitation of secretory products on ductal epithelium, the increased formation of plugs, and the more frequent acinar atrophies suggest the development of significant tissue injuries.

Multiresidue pesticide analysis by ion-trap mass spectrometry.

The ion trap has been demonstrated to be able to detect and quantify 245 target pesticides extracted via the Luke method while providing concurrent confirmation of presence via full scan data at the sub-ppm level. The precision and accuracy of the analytical approach was determined to be no greater than 15% relative standard deviation. A comparison study of over 100 incurred residues analyzed by the ion trap and gas chromatography with an array of element-selective detectors has indicated that sample clean-up will probably be necessary before quantification is acceptable for all target compounds. The data obtained using a combination of gas chromatography and mass spectrometry and presented for 250 target pesticides constitutes the basic information required to duplicate and extend the methodology.

Analysis of testosterone esters by tandem mass spectrometry.

The electron ionization (EI) and chemical ionization (CI) mass spectra of 12 representative testosterone esters were examined to explore the various analytical options available for identification and confirmation of the esters. Using EI, a number of fragment ions indicated the identification of the testosterone moiety, but structural confirmation of the individual esters often required the observance of the molecular ion at very low relative abundance ratios. The acceptable analytical method involved CI/tandem mass spectrometry based on the production of the 2 generic product ions derived from the protonated molecule ion.

Improvements in ion-trap chemical-ionization performance.

Ion-trap chemical-ionization performance has been improved by application of a modified scan function for the rejection of the undesired electron-ionization-like (EI-like) ions formed at the beginning of the reaction ionization period. The net effect of this software modification to the automatic reaction control is to produce chemical ionization (CI) spectra that are no longer adulterated with concentration-dependent EI-like ions. Under such improved conditions, CI spectra from an ion trap can now be directly compared with CI spectra produced on conventional quadrupole and magnet-scanning instruments.

[Correlation between acinar cell fat accumulation and secretory capacity of the rat pancreas in the early stage of alcohol-induced pancreatopathy]. / Zusammenhang zwischen Azinuszellverfettung und sekretorischer Kapazität des Rattenpankreas im Frühstadium einer alkoholinduzierten Pankreatopathie.

In patients exhibiting chronic alcohol abuse, the accumulation of fat droplets in pancreatic acinar cells, as well as changes in pancreatic secretion, can be interpreted as early signs of pancreatic damage. Using rats, (the animals were fed for 9 +/- 1 months with a solution of 20% v/v ethanol, combined with either a normal or a fat enhanced diet) we tested whether or not these symptoms are related both to each other and to morphological lesions of the tissue. Based on six separate histological criteria, the lesions were classified into five stages of severity. In order to characterize the secretory capacity of the pancreas, we measured the outputs of lipase, alpha-amylase, trypsin, chymotrypsin, carboxypeptidase A, elastase, and phospholipase A. Compared with the control group, we found that the alcohol-fed animals exhibited a significantly higher degree of morphological damage to the pancreas, as well as an increased frequency of fat accumulation in the acinar cells, and, with the exception of alpha-amylase, a rise in the level of enzyme secretion. In the animals exhibiting the highest degree of tissue damage, however, both fat accumulation and hypersecretion appeared to be diminished. This diminution could possibly be interpreted as the first sign of chronic pancreatitis. Increased consumption of fat did not change either the level of fat accumulation in the acinar cells, or the level of pancreatic secretion. Within the group of alcohol-fed rats, the most pronounced levels of hypersection were found in animals exhibiting cellular fat accumulation. However, the secretion levels of the alcohol-fed animals exhibiting no such fat accumulation did not differ significantly from that of the control group. Therefore, a relationship appears to exist in rats between fat accumulation in acinar cells and the level of pancreatic secretion.

[Exocrine function of a heterotopically transplanted pancreas segment in humans]. / Die exokrine Funktion eines heterotop transplantierten Pankreassegmentes des Menschen.

Pancreatic secretion is involved in circadian regulation of the whole organism. This observation was obtained in animals and humans with pancreatic fistulas. We report on three patients in whom the pancreas was removed totally or subtotally because of chronic pancreatitis with severe pain. A segment of the removed gland was transplanted into the thigh in order to preserve endocrine function. The pancreatic duct was drained by a polyethylene tube until pancreatic duct occlusion. Postoperatively juice volume increased within 3 days and remained constant afterwards with 300 ml in 24 hours. Secretin, cholecystokinin and food intake are able to stimulate the transplanted segment in a typical manner. The secretion showed circadian changes. In all patients the pancreatic juice content of protein, amylase, trypsinogen, calcium, and zink decreased till 11 p.m. After 11 p.m. the content of all substances increased and reached maximal values at 6 a.m. Flow rates and therefore output per minute decreased greatly till 6 a.m. The large juice volume of 300 ml in 24 hours is perhaps the consequence of a break down of the feedback mechanism between intraduodenal trypsin activity and CCK-release. The changes during the night may be of pathogenetic relevance. In the early morning pancreatic juice is highly concentrated and the flow rate is very low. High protein concentrations, high calcium concentrations, and reduced flow rates may lead to protein and calcium carbonate precipitates. This mechanism is under discussion in the pathogenesis of chronic pancreatitis.

Confirmation of trace level residues in the food supply.

With the recent proliferation of mass spectrometric methods available for the identification and confirmation of various compounds in different environmental matrices, it is timely to address the criteria desirable in a regulatory sample case. The emphasis of this review is on the experimental process of confirmation at concentration levels in the range of low parts per million (ppm) to parts per trillion (ppt). At such levels, various data manipulations or alternate choices of approaching the analytical problem of confirmation must be employed to ensure an acceptable result. The problems experienced when dealing with nanogram levels in analysis are much more complex than when recording a mass spectrum of an ample supply of a reference standard. This review reflects an interpretation of the developing status of confirmation since there does not yet exist "accepted criteria".

Potential misidentification of trichlorophenylethanol in imported peppers.

During regulatory analyses for the determination of pesticide residues on agricultural commodities, a frequently encountered trichlorinated compound was misidentified by the NBS library search routine. This case history illustrates the need for more rigorous confirmation criteria when dealing with multi-chlorinated compounds where fragmentation can be dominated by methyl loss followed by loss of CO and HCI.

[Changes in pure human pancreatic juice in chronic pancreatitis]. / Veränderungen im reinen menschlichen Pankreassaft bei chronischer Pankreatitis.

Investigations of pancreatic juice revealed new insights into the pathogenesis of chronic pancreatitis (cP). But many results are contradictory. In this paper pure human pancreatic juice from patients with cP (n = 14) was compared with results obtained from normal subjects (n = 22). The pancreatic juice was obtained endoscopically recording the absorption (280 nm) simultaneously. By means of this special technique 4 fractions could be exactly distinguished: 1. wash-out-period, 2. phase of secretin action, 3. phase of pancreozymin (CCK) action, and 4. post-CCK-phase. Total protein, trypsinogen, zinc sodium, and potassium were determined. In fraction 1 (wash-out-period) mean values of protein, trypsinogen and zinc are lower in patients with cP compared with control subjects. In case of zinc the difference is statistically significant. In fraction 2 (secretin-phase) no differences could be detected between cP and control subjects. In contrast in fraction 3 (CCK-phase) mean values of protein and trypsinogen are lower in control subjects than in patients with cP. But the standard deviations are so high that all differences are not statistically significant. The results indicate that under fasting conditions the pancreatic juice content of protein, trypsinogen and zinc is lower in patients with cP. But patients with cP can be stimulated much better with CCK than control subjects. Till now such a different behaviour during wash-out-period and CCK-stimulation is not reported in the literature.

[Lymph drainage disorder as a pathogenetic co-factor in acute pancreatitis?]. / Lymphdrainagestörung als pathogenetischer Co-Faktor der akuten Pankreatitis?

Experiments performed on 71 Wistar rats confirm that preexisting interruption of lymph drainage by ligation of the ductus thoracicus can have a major influence on the development of pancreatitis. The effect of a ductus hepatopancreaticus blockade in experimental group A (32 animals) was greatly exacerbated by previous ligation of the ductus thoracicus (experimental group B; 34 animals). Edema of the interstitial pancreatic tissue led to lipolytic necrotizing pancreatitis with a slight hemorrhagic component, increasing ascites after the 12 th hour of the experiment, and numerous abdominal fat necroses after about 19 hours, but only relatively minor necroses of acinar parenchyma cells in the pancreas. Fat tissue necroses were only found in almost 20% of the animals in group A, and these probably resulted from manipulation of the duodenum during the implantation of a shunt to divert the bile, whereas they were found in all animals of group B after the 19th hour of the experiment, usually in large numbers. The sometimes considerable increases in serum amylase and particularly lipase activity were caused by obstruction of the efferent ducts, but did not increase appreciably after disturbance of the lymph drainage systems. On the contrary, under these circumstances, drainage of the salivary edema via the peritoneal mesothelium and into retroperitoneal fat tissue must be considered responsible for ascites and the initiation of fat cell necroses by lipase and other enzymes.

[An improved method for the microencapsulation of liver microsomes for use in extracorporeal detoxication]. / Ein verbessertes Verfahren für die Mikroverkapselung von Lebermikrosomen zur Anwendung in der extrakorporalen Detoxikation.

Rat liver microsomes were microencapsulated in a pure aqueous medium by means of a new technique. The wall of the microcapsules consists of a semipermeable simplex membrane which is stabilized mainly by electrostatic interactions between a polymeric polyanion (sodium cellulose sulphate) and a polymeric polycation (polydimethyldiallylammonium chloride). The metabolic as well as the mechanic parameters of the microcapsules could be markedly improved by separating the metabolic (liver microsomes) from the membrane component (sodium cellulose sulphate) in such a way that two distinct compartments are formed during the preparation of the microcapsules.

Screening by tandem mass spectrometry for trace levels of alkylbenzenes.

Product ion spectra derived from molecule ions as the precursor ions for 14 alkylbenzenes have been studied under electron ionization and methane chemical ionization. The data have provided a satisfactory screening method for both detection and confirmation of such compounds at low parts per million levels.

Residue characterization of triadimefon in grapes by gas chromatography and mass spectrometry/mass spectrometry.

A field study of the use of the new fungicide triadimefon (Bayleton) on grapes has indicated that residue levels of 0.01 ppm may be expected on the ripe fruit in spite of the 60-75 day interval from spray to harvest. Triadimefon and its primary metabolite triadimenol (Baytan) have been characterized by gas chromatography and mass spectrometry to provide identification down to a detection level of 0.001 ppm. Recovery studies on these fungicides have indicated that they are completely extracted by the single multi-residue analytical methodology presently in use for monitoring fresh produce.

[The determination of trypsin activity in duodenal fluid with N alpha-(p-toluenesulfonyl)-L-arginine-p-nitranilide (L-TAPA)]. / Die Bestimmung der Trypsinaktivität im Duodenalsaft mit N alpha-(p-Toluensulfonyl)-L-arginin-p-nitranilid (L-TAPA).

The conditions are optimized for the determination of trypsin activity in duodenal juice at 37 degrees C using L-TAPA as a substrate ("Bio-La-Test Trypsin", Lachema, CSSR). Most of the directions of the kit could be accepted, but optimal pH was 0.4 units below that described there. This method allows a highly specific, sensitive, and sufficiently precise determination of trypsin activity in duodenal juice.

Characterization of benzyl isothiocyanate and phenyl acetonitrile from papayas by mass spectrometry.

Two unidentified analytical responses in a papaya extract were structurally determined by mass spectrometry to be benzyl isothiocyanate and phenyl acetonitrile. Both these compounds have previously been shown to result from degradation of benzylglucosinolate that occurs naturally in the seeds of the fruit. Characterization by mass spectrometry has now provided a convenient mechanism to detect both these degradation compounds in extracts resulting from routine pesticide residue analysis.