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Biomedical subjects

J Freise

Publications and source records attributed to J Freise.

At least 37 records · Page 2Linked to original sources

Gabexate mesilate and camostate: new inhibitors of phospholipase A2 and their influence on the alpha-amylase activity in serum of patients with acute pancreatitis.

The new synthetic polyvalent protease inhibitors gabexate mesilate (ethyl-p[6-guanidinohexanoyloxy]-benzoate methansulfonate) and camostate (N,N-dimethylcarbamoylmethyl-4-[4-guanidinobenzoyloxy]-phenylacetate methansulfonate) were tested for possible inhibition of phospholipase A2 activity. In a pilot study, we treated 17 patients suffering from acute pancreatitis with continuous intravenous administration of gabexate mesilate, 450 mg/d. The results were compared with a placebo group (same standard therapy) of 21 patients suffering from acute pancreatitis. In vitro experiments showed that, at concentrations between 10(-4) and 5 X 10(-4) mol/L (depending on the enzyme assay employed) for gabexate mesilate and between 10(-3) and 5 X 10(-4) mol/L for camostate, a 50% reduction in phospholipase A2 activity was effected. Comparing the two groups of acute pancreatitis patients after 6 days of treatment with gabexate mesilate, we observed a statistically significantly lower alpha-amylase activity in the serum of treated patients compared with the placebo group.

Acute Disease↗

[Is a timely diagnosis possible in pancreatic cancer?].

The incidence of pancreatic cancer, the incidence rate of physicians in a given area, the sensitivity and specificity of morphological (ERCP, CT, sonography), cytological and serological (CEA, alpha-fetoprotein, POA, R-nase, LAI, CA 19-9) examination methods were used (taking the cities of Ulm and Hannover as basis) for calculating that a general practitioner, or a practising internist, may be able to diagnose a case of pancreatic cancer about 3-4 times during his professional career, and at the most once only one early cancer. There is at present no screening method. Diagnosis of an early cancer entirely free from any symptoms, is a mere coincidence. When the first uncharacteristic complaints become manifest, the pancreatic cancer is already 3 to 5 years old; usually, it can then no longer be classified as an early cancer.

Cholangiopancreatography, Endoscopic Retrograde↗

[Width of the lumen of the common bile duct: sonography compared with ERCP].

The diameter of the common bile duct can be easily determined by ultrasound and by ERCP (endoscopic retrograde cholangiography). The measured values differ by as much as 20% due to the technical features of both methods. A study with 100 patients showed that in 20% of the patients the diameter of the common bile duct determined by ERCP was twice that of the value determined by sonography. The difference can be definitely explained by the influence of butyl scopolamine and the high-pressure injection of the contrast medium into the bile duct system. The sonographic measured size of the common bile duct is correlated with the physiological value but a sure prediction of the expected value to be determined by ERCP is not possible.

Cholangiopancreatography, Endoscopic Retrograde↗

[Gallstone formation following transmural migration of a surgical clip in the bile ducts. Case report].

Foreign bodies as a nucleus for precipitation of gall-stones are not frequently observed. The combination of primary immigrated foreign bodies into the bile ducts and following encasing by a gall-stone could be even more rarely found. A case report is presented concerning a patient, in whom a hemo-clip was fixed away from the bile-ducts in connection with a cholecystectomy and revision of the common bile-duct. After hospital admission because jaundice in the PTC was found a prepapillary concrement with a central hemo-clip, which has served as a nucleus for precipitation after transmural immigration.

Cholecystectomy↗

[Chronic pancreatitis: sensitivity, specificity and predictive value of the pancreolauryl test].

Assessment of the clinical value of the pancreolauryl test (PLT) in the literature range from "useless" to a specifity of 95% and a sensitivity of 98%. In this work, our own data are presented in relation to various reference methods. The results are derived from the largest collective investigated to data, comprising 40 controls and 391 patients (108 with chronic pancreatitis and 283 with other gastrointestinal disorders). The specifity of the the PLT varies between 81% and 95% according to the "quality" of the control collective. The PLT is particularly frequently pathological in patients with diseases in the region of the gallbladder/bile duct and the gastrointestinal tract. The sensitivity of the PLT for chronic pancreatitis varies between 68% and 100%, depending on 9 different reference methods employed. Based on the prevalence of chronic pancreatitis with exocrine insufficiency in various patient collectives, the predictive value of the PLT for the presence of this disorder can be calculated using our data.

Cholangiopancreatography, Endoscopic Retrograde↗

[Therapy of acute pancreatitis with a synthetic protease and phospholipase A2 inhibitor gabexate mesilate].

In order to evaluate the efficacy and safety of gabexate mesilate (FOY = [ethyl-4-(6-guanidinohexanoyloxy) benzoate methane sulfonate]), a synthetic inhibitor of various proteases as well as phospholipase A 2, 17 patients with acute pancreatitis were treated with FOY in doses of 3 X 150 mg/day per i.v. perfusor. The clinical course of the disease and the laboratory findings were compared with the results of a control group of 21 patients also suffering from acute pancreatitis. 30% of the patients in the FOY-group and 40% in the control group had different complications during the first week after admission to the hospital. The laboratory findings in the two groups revealed that alpha-amylase levels in serum and urine in the FOY-group were significantly lower than in the control group. Side effects of the drug were not observed. FOY may be considered a promising drug for treatment of acute pancreatitis in view of its few side effects and especially with regard to its mode of action.

Acute Disease↗

Inhibition of phospholipase A2 by gabexate mesilate, camostate and aprotinine.

Gabexate mesilate (FOY, ethyl-p-[6-guanidino-hexanoyloxy]-benzoate-methanesulfonate), camostate (N,N-dimethyl-carbamoylmethyl-4-[4-guanidinobenzoyloxy]-phenylacetate), methanesulfonate (FOYPAN) and aprotinine (Trasylol) were tested for possible inhibition of phospholipase A2. Gabexate mesilate at a concentration of 5 x 10(-4) mol/l and camostate at a concentration of 10(-3) mol/l caused a 50% reduction in enzyme activity. There was no inhibition by aprotinine at clinical doses; 40 million KIU/l were necessary to reduce phospholipase A2 activity by 20%.

Animals↗

Accumulation of insulin and glucagon in the liver (via portal vein catheter or with liposomes) does not stimulate liver cell regeneration after partial hepatectomy in normal or portocaval shunted rats.

The regenerative activity of the liver parenchyma after two-thirds hepatectomy was examined in normal rats and rats with a fresh or 7-day-old portocaval shunt. The parameter for regeneration was the incorporation of 3H-thymidine into DNA. The exogenous supply of insulin and glucagon--both potential stimulators of regeneration--by permanent infusion into the portal vein, or by several injections of the liposome-encapsulated hormones, did not significantly stimulate the rate of regeneration normally controlled by endogenous pancreatic hormones.

Animals↗

Pharmacokinetics of liposome encapsulated cisplatin in rats.

The chemotherapeutic anticancer agent Cisplatin--cis-diamine-dichloroplatinum (II)--has several disadvantages, such as its extreme nephrotoxicity, fast elimination via the kidneys, and rapid binding to plasma proteins. Encapsulation into negatively charged, multilamellar liposomes (MLV), composed of egg-lecithin: cholesterol: dicetylphosphate in 5:5:1 molar ratio, causes drastic changes in behavior after a single i.v. injection: marked increase in the circulation half life paralleled by slower urinary excretion; remarkedly higher levels of free drug in the blood; increased uptake in liver, spleen and lymph nodes, and decreased uptake in skin and bones. In the kidneys a reduced and retarded uptake over 15 hr, then a higher uptake was found. The liposomal Cisplatin has a strong transitory diuretic effect, which nevertheless is not paralleled by other signs of renal injury such as decreased output of creatinine or increased output of protein or urinary enzymes. By pre-ejection of empty liposomes the diuresis can be reduced and the additional Pt deposit in the kidneys prevented.

Animals↗

Uptake of liposomes and sheep red blood cells by the liver and spleen of rats with normal or decreased function of the reticuloendothelial system.

The distribution of negatively charged liposomes in rats with normal or depressed function of the liver RES was examined. RES activity was determined by the uptake of the sheep red blood cells (SRBC). Whereas pretreatment with colloidal carbon or dextran sulphate drastically diminishes the SRBC uptake by the liver, the liposome uptake is decreased by 12-15% only. In the spleen, such pretreatment boosts the SRBC uptake five- to sixfold, whereas liposome uptake was decreased by about 50%. This indicates that phagocytosis by the RES is only of several liposome-cell interactions. Consequently, the suppression of the RES function is of no practical use when attempting to suppress the preferential liposome uptake by the liver and spleen.

Animals↗

Influence of a portacaval shunt on the distribution of 14C-chol-PC-DCP-liposomes and liposome entrapped 3H-methotrexate in the organs of rats.

The individual roles of hepatic parenchymal cells and non-parenchymal cells in the uptake of intravenously injected liposomes by the liver have not yet been clearly determined. Experimentally, it is suggested that a portacaval shunt reduces the phagocytic capacity of the liver RES. In our experiments a portacaval shunt does not influence the hepatic uptake of 14C-Chol-PC-DCP-liposomes and the liposome entrapped 3H-Methotrexate in rats. In normal rats and in rats with a portacaval shunt, most of the 14C- and 3H-radioactivity is found in the liver and the ratio between the amounts of free and liposome entrapped radioactivity 3 to 15 hours after i.v. injection is approximately 1:10. Therefore, it is concluded that the liver RES does not play an integral role in the enrichment of liposomes in the liver.

Animals↗

[Ultrasound in the diagnosis of ileitis terminalis Crohn (author's transl)].

In order to check the value of sonography in the diagnosis of Crohn's disease, 81 patients who suffered from Crohn's disease were examined by means of real-time B-mode ultrasound. Bowel wall infiltration along the terminal ileum that could be shown to involve the coecum as well, appeared to be a reliable parameter in the diagnosis of Crohn's disease. This finding was most pronounced in acute disease whereas in chronic or mild disease, characteristic signs of Crohn's disease were absent. Among the complications of Crohn's disease formation of intraabdominal abscesses can be demonstrated by sonography. From our results we propose to employ diagnostic ultrasound in the acute stage of disease. After remission the diagnosis should be confirmed by endoscopy and X-ray examinations.

Abscess↗

"In vivo" distribution of liposomes between parenchymal and non parenchymal cells in rat liver.

The in vivo uptake of 3H-methotrexate containing, 14C-cholesterol labelled liposomes was determined for the two major liver cell populations, parenchymal cells (PC) and non-parenchymal cells (NPC) after intravenous injection of the liposomes into normal rats and rats with a portocaval shunt, followed by isolation and purification of the two cell types. One hour after injection, the purified NPC had bound 2-3 times more of the liposome-attached radioactivity per cell than the purified PC, whereas 6 hours after injection the ratio was inverted. In animals with a portocaval shunt, the PC contained 3-4 times more liposomal radioactivity per cell than NPC already 1 hour after injection, although the total uptake by the whole liver was not diminished under these conditions. Recalculating the data obtained from the isolated cells for the whole liver, it is found that 1 hour after injection the liver NPC had bound the same amount of liposomal radioactivity as liver PC, although they account for only 7% of the liver volume. After 6 hours, the PC had bound 5 times more liposomal radioactivity than the NPC; this ratio is achieved in animals with a portocaval shunt already 1 hour after injection. This shift is simultaneously caused by a gain of PC-bound radioactivity and decrease of NPC-bound radioactivity.

Animals↗