Biomedical subjects

Hans Lippert

Publications and source records attributed to Hans Lippert.

40 records · Page 3Linked to original sources

PubMed2002

Soluble thrombomodulin plasma levels are an early indication of a lethal course in human acute pancreatitis.

BACKGROUND: The potential to predict severe disease and lethality by using plasma soluble thrombomodulin (sTM) and C-reactive protein (CRP) levels in 73 patients with acute pancreatitis was analyzed in a prospective 5-year investigation performed at a single institution. METHODS: According to the Atlanta criteria, pancreatitis was classified as mild in 23 patients and as severe in 50 patients. Blood was collected on days 1, 3, 5, 7, 10, 14, 21, and 28 after the onset of pain and analyzed for sTM and CRP. RESULTS: During the period between days 3 and 10 of acute pancreatitis when most of the admissions occurred, sTM levels at a cutoff of 75 ng/mL on day 3 (sensitivity, 100%; specificity, 77%; positive predictive value, 38%; negative predictive value, 100%) and 71 ng/mL on day 10 (sensitivity, 100%; specificity, 77%; positive predictive value, 41%; negative predictive value, 100%) were predictive of a lethal outcome. With sTM levels, it was not possible to differentiate patients with mild pancreatitis from those with severe pancreatitis (Atlanta classification). In contrast, CRP levels at a cutoff of 113 mg/L on day 3 differentiated severe from mild courses with a diagnostic sensitivity of 84%, a specificity of 60%, a positive predictive value of 78%, and a negative predictive value of 69%. CRP levels at a cutoff of 122 mg/L on day 10 differentiated mild from severe courses (nonsurvivors) with a diagnostic sensitivity of 72%, a specificity of 72%, a positive predictive value of 86%, and a negative predictive value of 53%. In contrast, differentiation of mild forms of acute pancreatitis from severe pancreatitis (survivors) on day 10 was not possible. CONCLUSIONS: CRP is a valuable marker of disease severity in acute pancreatitis especially in the first period of pancreatitis, whereas sTM identifies early those patients with the most severe courses and a high risk of dying (negative predictive value, 100%). Determination of sTM in addition to CRP offers the opportunity of identifying early those patients who require intensive care most urgently. Of course, further investigations of sTM in acute pancreatitis are indicated to confirm our results.

Acute Disease↗

PubMed2002

Trypsin activity is not involved in premature, intrapancreatic trypsinogen activation.

A premature and intracellular activation of digestive zymogens is thought to be responsible for the onset of pancreatitis. Because trypsin has a critical role in initiating the activation cascade of digestive enzymes in the gut, it has been assumed that trypsin also initiates intracellular zymogen activation in the pancreas. We have tested this hypothesis in isolated acini and lobules from rat pancreas. Intracellular trypsinogen activation was induced by supramaximal secretagogue stimulation and measured using either specific trypsin substrates or immunoreactivity of the trypsinogen activation peptide (TAP). To prevent a trypsin-induced trypsinogen activation, we used the cell-permeant, highly specific, and reversible inhibitor Nalpha-(2-naphthylsulfonyl)-3-amidinophenylalanine-carboxymethylpiperazide (S124), and to prevent cathepsin-induced trypsinogen activation, we used the cysteine protease inhibitor E-64d. Incubation of acini or lobules in the presence of S124 completely prevented the generation of trypsin activity in response to supramaximal caerulein but had no effect whatsoever on the generation of TAP. Conversely, when trypsin activity was recovered at the end of the experiment by either washout of S124 from acini or extensive dilution of lobule homogenates, it was up to 400% higher than after caerulein alone and corresponded, in molar terms, to the generation of TAP. Both trypsin activity and TAP release were inhibited in parallel by E-64d. We conclude that caerulein-induced trypsinogen activation in the pancreas is caused by an E-64d-inhibitable mechanism such as cathepsin-induced trypsinogen activation, and neither involves nor requires intracellular trypsin activity. Specific trypsin inhibition, on the other hand, prevents 80% of trypsin inactivation or autodegradation in the pancreas.

Acute Disease↗

PubMed2002

Tumor cell dissemination during laparoscopy: prevention and therapeutic opportunities.

Port-site recurrences (PSRs) are abdominal wall recurrences that occur in the subcutaneous tissue within a trocar site after cancer laparoscopy and are not associated with peritoneal carcinomatosis. In order to develop PSRs, viable tumor cells must be liberated from the primary tumor, be transported to a wound, and find there a favorable environment for growth. The short clinical delay in the occurrence of PSRs and their size suggest massive cell seeding into the abdominal wall. Traumatic handling of the tumor, slipping of trocars, liquid projection, as well as poor extraction techniques can all cause implantation of malignant cells into the subcutaneous tissue. Such contact can also occur postoperatively if the trocar channels remain open. Some histologies (e.g. gallbladder adenocarcinoma), the presence of ascites and advanced tumor stage are risk factors for PSRs. Further conditions--including the use of gas--might also play a limited role. The first preventive measure is the correct indication for a laparoscopic approach. Several techniques have been demonstrated to prevent PSRs in the animal model: (a) fixation of trocars to the abdominal wall; (b) prevention of leakage; (c) careful specimen handling; (d) reducing trauma to the abdominal wall; (e) specimen isolation before extraction from the abdominal cavity; (f) trocar-site irrigation with a cytotoxic solution, and (g) closure of peritoneum. Further innovative therapies are currently under investigation. In the clinical setting, correct indication, surgical expertise and application of prophylactic measures seem to be the best way to prevent the occurrence of PSRs.

Abdominal Wall↗

PubMedDate not supplied

Intraperitoneal treatment using taxol is effective for experimental peritoneal carcinomatosis in a rat model.

Following resection of colorectal carcinoma, a considerable local recurrence rate within the previous tumor bed or at the peritoneal site remains an unsolved problem. Currently, there are no established protocols for the treatment or prevention of peritoneal carcinomatosis. Taxol showed benefit in patients with advanced tumor growth, in particular, gynecological carcinomas. Taxol was used to test whether it can either prevent or treat peritoneal tumor growth derived from colon carcinoma. In rats divided in 3 groups, peritoneal carcinomatosis was induced by tumor cell transfer: Taxol (170 mg/m(2)) was given i). directly (group A); ii). on days 5, 10, 15 postoperatively (representing early administration; group B), or iii). as late intraperitoneal (i.p.) chemotherapy (15, 20, 25 days following surgery; aiming for reduction of a manifest peritoneal carcinomatosis; group C) into the abdominal cavity. Tumor growth was quantified by tumor weight of the greater omentum and the mesenteric site, number of detectable tumor lesions, occurrence of hepatic and pulmonary metastases and the amount of ascites. Taxol was highly effective in preventing or reducing i.p. tumor spread when the drug was given directly or within a short time interval after tumor cell implantation (groups A and B), whereas no significant antineoplastic potential was found in the treatment of an established peritoneal carcinomatosis. In conclusion, Taxol appears to be a promising chemotherapeutic agent to be investigated in further detail with possible potential for a later human phase-I trial in peritoneal carcinomatosis.

Adenocarcinoma↗