Determination of kallikrein by radioimmunoassay in human body fluids.

A sensitive and specific radioimmunoassay for human urinary kallikrein was developed, which allows tissue kallikrein determination in human urine, saliva, pancreatic juice, bile and sweat. In several body fluids a kallikrein-like antigen was found, but not in gastric juice and breast milk. According to gel filtration studies, complex formation of kallikrein with serum proteins or different molecular weight forms of kallikrein in serum and urine may be assumed. Pancreatic kallikrein secretion follows the same pattern after stimulation with secretin and cholecystokinin as trypsin and chymotrypsin in normal individuals. In chronic pancreatitis the kinetic behaviour remains unchanged with respect to the enzyme secretion, but the secretion of kallikrein is reduced to about 20%.

[Hemostatic properties of gastric juice under basal conditions and after stimulation with pentagastrin or secretin-pancreozymin (author's transl)]. / Hämostaseologische Eigenschaften des Magensaftes und deren Beeinflussung durch den Pentagastrin- und Sekretin-Pankreozymin-Test.

Unsoluble gastric mucus and gastric juice from 11 normal volunteers were separated by centrifugation and investigated for hemostatic properties. Unsoluble gastric mucus added to citrated blood shortened reaction time and increased duration of maximum amplitude of thrombelastographic recordings, indicating an acceleration of hemostatic processes. On the other hand gastric juice inhibited coagulation and enhanced fibrinolytic activities, as shown by thrombelastographic recordings, prothrombin time, partial thromboplastin time, and euglobulin lysis time. Unsoluble gastric mucus accelerated hemostasis even more after stimulation by secretin-pancreozymin, as evidenced by thrombelastographic recordings. Gastric juice of patients with duodenal ulcers showed a significant change of these parameters to the opposite after pentagastrin. We conclude, that stimulation respectively inhibition of HCl and proteases, following pentagastrin respectively secretin-pancreazymin may influence hemostatic properties of gastric juice and gastric mucus as well.

[Study on the genesis of diffuse intravascular coagulation after implantation of a peritoneal-jugular le veen shunt (author's transl)]. / Untersuchungen zur Frage der Genese der diffusen intravasalen Gerinnung nach Implantation des peritoneal-jugularen Shunts nach Le Veen.

In a 68-year-old woman with cirrhosis of the liver an attempt was made to treat the intractable ascites by a peritoneal-jugular shunt. In the course of the two-week continuous reinfusion of ascites a disseminated intravascular coagulation (DIC) developed which made a ligation of the shunt necessary. After ligation the fibrinogen and platelets rose to normal levels. To evaluate the relationship of the DIC to the continuous reinfusion of ascites, a coagulation profile of the ascitic fluid of a number of patients was performed. It could be demonstrated that the procoagulant activities and factors inhibiting coagulation varied widely although, in some cases, procoagulant factors predominated. Furthermore, in the ascitic fluid of the one patient described in detail activation of the contact factor could be shown following implantation of the shunt. The results of these investigations suggest that in future candidates for a Le Veen shunt, in vitro clotting tests should be performed of the ascitic fluid and a probatory reinfusion of a large amount of ascitic fluid with a parallel evaluation of the most important clotting parameters. A patient at risk to develop DIC following the insertion of a Le Veen shunt perhaps could thus be recognized prior to such a procedure.

Quantitative correlation between the Dane particle-associated DNA polymerase and the hepatitis B e antigen.

In order to evaluate the potential infectivity of blood of hepatitis B patients, the Dane particle associated DNA polymerase was determined, which is a reliable marker for the presence of complete viral particles. Enzyme activities were compared with hepatitis B e antigen (HBeAg) titers determined by radioimmunoassay. Detectable DNA polymerase activity was only present in HBeAg positive blood, preferentially in samples with high antigen titers (1 : 1000 and above). These samples therefore have to be considered as highly infectious. However, blood with low HBeAg levels and free of detectable polymerase activity can still be infectious, since the polymerase reaction is rather insensitive compared to the radioimmunological HBeAg determination.

[Validity of hepato-biliary functional scintigraphy using 99mTc-diethyl-IDA (author's transl)]. / Die Wertigkeit der hepatobiliären Funktionsszintigraphie mit 99mTc-Diaethyl-IDA.

99mTc-DAIDA is superior to other cholotropic radiopharmaceuticals. As radiochromatographic examinations with various systems showed, it is secreted by the hepatocytes into the bile as an unchanged anion. In a study of hepato-gastroenterologically selected patients (n = 45) values for liver function parameters such as Tmax' T/2, time of appearance in gall-bladder and duodenum were in the group of patients without any hepato-biliary disease (x +/- S.D.): 15.5, +/- 5.2 min, 30.8 +/- 8.2 min, 13.5 +/- 6.1 min, and 22.0 +/- 10.8 min. The clearance determined after comparison of different defining regions and types of calculation in this group was 323.8 +/- 145.8 ml/min x 1.73 m2 (x +/- S.D.); the renal excretion competitive with the hepato-biliary elimination amounted within 51 min p.i. to 5.15% of the injected activity. The values of the several time-parameters as well as the participation of the kidneys in the 99mTc-DAIDA excretion increased substantially in patients with intrahepatic jaundice, but only slightly in the group of other liver cell diseases. It was not possible to determine the various liver function values in patients with extrahepatic jaundice. Because of their large spread within the different groups these parameters were without diagnostic relevance in the individual case. The hepato-biliary sequential scintigraphy with 99mTc-DAIDA appears to find its main use in morphologic diagnostics.

[Hepatitis risk to dentists. Studies on the frequency of hepatitis in dentists in the Munich region and in the district of Upper Bavaria]. / Hepatitis-Risiko bei Zahnärzten. Untersuchungen zur Hepatitis-Häufigkeit bei Zahnärzten im Raum München und im Regierungsbezirk Oberbayern

Dentists have a particular risk of acquiring viral hepatitis because of their close contact with blood and saliva during dental manipulations--especially as the majority of dentists do not use gloves during work and often have small cuts and abrasions on their hands. On the other hand personnel in the dentist's office offers several potential modes of parenteral and oral-intestinal transmission of hepatitis. In order to find out the risk of dentists exposing themselves to hepatitis-infection (especially hepatitis B-infection) we performed a questionnaire-study among practicing dentists all over Oberbayern. 858 replies were received after distribution of 1030 questionnaires (participation: 83.3%) and could by analyzed. 116 dentists had had a hepatitis during their professional work (13.5%). The frequency of hepatitis among the younger colleagues--who were practicing from 1 to 14 years--was about 5%. The number of hepatitis-infections increased continually up to 33% after 35--39 years of professional activity. In a second study blood samples were taken from 773 dentists and were tested for HB3Ag by radioimmunoassay. Of these 773 blood samples taken 25 (3.5%) were found to be antigen-positive. Compared to the general population the risk of infection is 6- to 30 times higher in dentists. The challenge of hepatitis-virus-infection can at present be met only-and at least in part-by scrupulous attention to prophylactic measures, such as using disposable gloves, needles and syringes and in autoclaving all non-disposable equipment. Besides dental personnel and patients should be screened at regular intervals for the presence of HBsAG.

[Significance of serum alpha-fetoprotein determination. Experiences with our own radioimmunoassay]. / Bedeutung der Serum-Alpha-Fetoprotein-Bestimmung. Erfahrungen mit einem eigenen Radioimmunoassay

Alpha-fetoprotein (AFP) was determined by a new radioimmunoassay in the sera of patients with different liver diseases. Compared to a normal group (n = 140, AFP levels below 15 ng/ml), most elevated AFP concentrations were found in 18 patients with primary liver cancer (PLC), 7 of whom showed Ouchterlony-positive levels (above 10,000 ng/ml). In 3 cases with liver cirrhosis, PLC was first suggested by high AFP levels between 1000 and 3600 ng/ml and later confirmed by histology. On the other hand, only 6 from 15 patients with other primary tumors and liver metastasis had AFP concentrations between 20 and 111 ng/ml. In 90% of 102 patients with liver cirrhosis AFP levels below 20 ng/ml were determined, while 13 cases showed elevated values up to 134 ng/ml. A transitory AFP increase between 20 and 238 ng/ml was seen in 32% of 63 cases in the early stage of acute hepatitis but 65% of 31 these cases in follow-up studies. 3 of 7 cases of chronic hepatitis gave similar results. The maximal AFP levels developed following the maximal transaminase activities by 5-18 days and coincided with a decrease of cholinesterase activity. The radioimmunological determination of AFP is recommended for earlier detection of the development of PLC in liver cirrhosis patients.

[Uric acid and phosphate metabolism of the splanchnic region during equimolar parenteral infusion of fructose and glucose]. / Harnsaeure- und Phosphatstoffwechsel des Splanchnicusgebiets unter aequimolaren parenteralen Dosen von Fruktose und Glukose

When fructose and glucose (10 g/5 min., 0.5 g/kg x h) were infused into a peripheral vein, fructose exhibited a transient increase of splanchnic uric acid production. Since phosphate and oxygen uptake rose simultaneously, the effect was considered to be due to well-known cellular drop of nucleotide and phosphate concentrations.

[Utilization of glucose and fructose in human liver and muscle]. / Die Verwertung von Glukose und Fruktose in Leber und Muskel beim Menschen

Hepatic metabolic balances derived from arterio-hepatic-venous substrate differences and hepatic blood flow exhibited similar results during fructose infusion (10 g/5 min., 0.5 g/kg x h) as compared to those from the isolated perfused organ: a portion of 55% of splanchnic fructose uptake was accountable for splanchnic glucose production, 25% for splanchnic lactate and pyruvate production and 20% for glycogen - of fat - synthesis and endoxidation. In account of this hepatic metabolism of fructose, glucose homeostasis and insulin secretion almost maintained. However, the small insulin response did not reduce hepatic free fatty acid utilization to such an extent as to increase pyruvate oxidation. Accordingly, splanchnic production of lactate and pyruvate, descending from fructose was enhanced. Since hepatic-venous lactate: pyruvate substrate ratios did not change, the rise of the arterial redox couple could not be due to hepatic fructose metabolism. According to the findings from the isolated perfused organ, fructose seemed to be phosphorylated at a rate which was found to be 2 to 3-fold that of glucose as calculated from splanchnic utilization rates. This high rate of fructose uptake was reduced with increasing insulin levels. The rapid ATP breakdown was followed by an increment of splanchnic oxygen consumption. The larger energy demand seemed to be satisfied by an enhanced endoxidation of free fatty acids. Since diabetics failed to increase their insulin production, their hepatic fructose phosphorylation rate and consequently their hepatic oxygen demand were not limited. Preliminary results concerning metabolic balances from the human forearm during a steady state of fructose supply, underline the notion that fructose has some effects on intermediary metabolism of skeletal muscle. Accordingly, in juvenile diabetics an enhancement of glucose-, lactate- and pyruvate-uptake could be demonstrated.

[Oxygen, carbohydrate and fat metabolism of the splanchnic region under the influence of equimolecular parenteral doses of glucose and fructose]. / Der Sauerstoff-, Kohlenhydrat- und Fettstoffwechsel des Splanchnikusgebiets unter dem Einfluss äquimolarer perenteraler Dosen von Glukose und Fruktose

Hepatic metabolic balances derived from arterio-hepatic venous substrate differences and hepatic blood flow exhibited similar results during fructose and glucose infusion (10 g/5 min, 0.5 g/kg X h) as compared to those from the isolated perfused organ. Accordingly, in account of hepatic utilization of fructose glucose homeostasis and secretion maintained during fructose infusion. However, the smaller insulin response during fructose infusion did not reduce hepatic free fatty acid utilization to such an extend as to increase pyruvate oxydation. Thus, splanchnic production of lactate and pyruvate descending from fructose was enhanced leading to a 7-fold increase of arterial lactate concentration. Since hepatic venous lactate to pyruvate substrate ratios did not change, the rise of the arterial redox couple could not be due to hepatic fructose metabolism. According to the findings from the isolated perfused organ, fructose seemed to be phosphorylated at a rate which was found to be 2-3-fold that of glucose as calculated from splanchnic utilization rates. The rapid ATP-breakdown was followed by an increment in splanchnic oxygen consumption. The larger energy demand during fructose infusion seemed to be satisfied by an enhanced endoxydation of free fatty acids.

[Influence of parenteral fructose or glucose administration on uric acid formation and phosphate uptake of the human liver]. / Einfluss parenteraler Fruktoxe- bzw. Glukosezufuhr auf die Harnsäurebildung und Phosphataufnahme der menschlichen Leber

15 min. after intravenous administration of fructose (10 g/5 min, 0,5 g/kg/h) the hepatic uric acid production in healthy volunteers increased from 0,07 mg/100 g X min to 0,52 mg/100 g X min. After one hour the enhanced uric acid production was 0,3 mg 100 g X min. The enhanced uric acid production was accompanied by an increased hepatic phosphate uptake. The highest value was 13 mumol/100 g X min. During the control period the liver released small amounts of phosphate into the hepatic vein. The increased hepatic uric acid output correlated with an enhanced renal clearance, therefore the peripheral venous uric acid concentrations remained unchanged.

Suitability of non-glucose-carbohydrates for parenteral nutrition.

Postoperative parenteral nutrition can only be optimally effective if the characteristics of post-traumatic metabolism are taken into account. Two main possibilities are discussed for the carbohydrate component of parenteral nutrition during this phase: glucose with high doses of insulin or non-glucose carbohydrates (sugar substitutes) possibly in a suitable combination with glucose. The risks as well as the technical and organisational problems involved in the use of them are discussed and the authors prefer the second of the two alternatives. Possible side effects of non-glucose carbohydrates are pointed out and it is shown how these can be avoided by observing dose guidelines. So far a combination of frucose : glucose : xylitol in a ratio of 2 : 1 :1 with a total dose of 0.50 g/kg/hour has been studied most thoroughly. This combination normalises the fat metabolism and improves glucose tolerance without requiring exogenous insulin. Experiences with this combination as well as individual non-glucose carbohydrates on operated patients have been given continuously for up to 7 days and in some cases even for several weeks. No side effects, no deviations from a steady state and no abnormal changes of the laboratory values occurred. The authors are of the opinion that non glucose carbohydrates are necessary if the facilities for frequent blood sugar controls are not available.

[Technique and results of hepatic resection (author's transl)]. / Technik und Ergebnisse bei Leberresektion

12 major hepatic resections are described. There were two postoperative deaths. 4 patients received more than two blood units intra- or immediately postoperatively (maximal blood loss 5000 and 4400 ml resp.). In 5 patients the operative procedure was performed in hemodilution, in these patients the maximal transfusion rate ranged to one blood unit. In nearly all patients a subphrenic collection of bile, blood and secretion was observed, but this was well treated conservatively. The various operative procedures, the possibility to avoid blood loss during hepatic resection and the concept of biliary drainage are discussed.