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Biomedical subjects

F Wenger

Publications and source records attributed to F Wenger.

18 recordsLinked to original sources

Immunologic changes during minimally invasive surgery.

Although recent experimental and clinical trials have documented that postoperative inflammation and changes in different immunologic parameters are less pronounced after laparoscopic approaches in comparison to open surgery, it still remains unclear what influence the pneumoperitoneum itself has on immunologic defense and function. This is mainly due to the endpoints of the different studies which investigate changes in the so-called immunologic parameters (cell subunits, C-reactive protein, cytokines, catecholamines or other stress hormones in plasma samples) rather than analyzing immunologic functions, such as cell activation, production of proteins, cell proliferation or in vivo immune defenses. So far, especially in clinical trials, no correlation has been demonstrated between the changes in immunologic parameters and relevant postoperative clinical endpoints, such as postoperative complications. Thus further clinical prospective randomized studies with relevant clinical endpoints and additional investigations of immunologic parameters are needed to prove the consequences of either minimally invasive surgery or open procedures on postoperative immune functions.

C-Reactive Protein↗

PTK787/ZK 222584, a novel and potent inhibitor of vascular endothelial growth factor receptor tyrosine kinases, impairs vascular endothelial growth factor-induced responses and tumor growth after oral administration.

PTK787/ZK 222584 (1-[4-chloroanilino]-4-[4-pyridylmethyl] phthalazine succinate) is a potent inhibitor of vascular endothelial growth factor (VEGF) receptor tyrosine kinases, active in the submicromolar range. It also inhibits other class III kinases, such as the platelet-derived growth factor (PDGF) receptor beta tyrosine kinase, c-Kit, and c-Fms, but at higher concentrations. It is not active against kinases from other receptor families, such as epidermal growth factor receptor, fibroblast growth factor receptor-1, c-Met, and Tie-2, or intracellular kinases such as c-Src, c-Abl, and protein kinase C-alpha. PTK787/ZK 222584 inhibits VEGF-induced autophosphorylation of kinase insert domain-containing receptor (KDR), endothelial cell proliferation, migration, and survival in the nanomolar range in cell-based assays. In concentrations up to 1 microM, PTK787/ZK 222584 does not have any cytotoxic or antiproliferative effect on cells that do not express VEGF receptors. After oral dosing (50 mg/kg) to mice, plasma concentrations of PTK787/ZK 222584 remain above 1 microM for more than 8 h. PTK787/ZK 222584 induces dose-dependent inhibition of VEGF and PDGF-induced angiogenesis in a growth factor implant model, as well as a tumor cell-driven angiogenesis model after once-daily oral dosing (25-100 mg/kg). In the same dose range, it also inhibits the growth of several human carcinomas, grown s.c. in nude mice, as well as a murine renal carcinoma and its metastases in a syngeneic, orthotopic model. Histological examination of tumors revealed inhibition of microvessel formation in the interior of the tumor. PTK787/ZK 222584 is very well tolerated and does not impair wound healing. It also does not have any significant effects on circulating blood cells or bone marrow leukocytes as a single agent or impair hematopoetic recovery after concomitant cytotoxic anti-cancer agent challenge. This novel compound has therapeutic potential for the treatment of solid tumors and other diseases where angiogenesis plays an important role.

Angiogenesis Inhibitors↗

[Repair of inguinal hernia in the elderly. Results of the plug-and-patch repair with special reference to quality of life].

In a prospective study the perioperative results of plug-and-patch repair were investigated in patients > or = 65 years, and quality of life was assessed using the SF36 preoperatively and 3 months after the procedure in 34 consecutive patients. From August 1994 to February 1999 147 patients with a mean age of 73 +/- 5 years (65-92 years) were operated on using the plug-and-patch technique, mostly under local anesthesia (LA: n = 124, 84%, ITN: n = 23, 16%). Preoperative risk factors were alcohol consumption, hypertonus, diabetes mellitus, ischemic heart disease, smoking, cerebrovascular disease, hyperlipidaemia and pulmonary disease. Most of the patients were ASA II (ASA I: n = 14, 9%, ASA II: n = 82, 56%, ASA III: n = 51, 35%). No intraoperative complications occurred, postoperative complications consisted of superficial wound hematoma (n = 6, 3.7%) and infection (n = 1, 0.6%), seroma (n = 7, 3.8%), urinary retention (n = 3, 1.8%) and ilioguinal pain syndrome (n = 3, 3.8%). The total amount of postoperative analgesic consumption was 4.9 +/- 1.8 g Novalgin for about 4 +/- 3 days. The duration of postoperative hospitalization was 2 +/- 1 days and limitation of daily activities 6 +/- 3 days. Clinical examinations after 3 months revealed no recurrence or late complications. Investigation of quality of life showed a significant improvement in the SF36 domains of physical activity, pain, vitality, and social functioning after the operation. No significant change was observed for physical, emotional, and global health.

Adult↗

The impact of laparoscopy with carbon dioxide versus helium on immunologic function and tumor growth in a rat model.

BACKGROUND: The pathogenesis of port site recurrences after laparoscopic surgery for malignant disease is still unknown. Whether different gases used to establish pneumoperitoneum have an influence on immunologic function and therefore on promotion of tumor growth has not yet been investigated. METHODS: Tumor growth of colon adenocarcinoma DHD/K12/TRb was evaluated in a rat model after insufflation either with CO2 (n = 25) or helium (n = 25) and in a control group (n = 25). Tumor growth was measured subcutaneously and intraperitoneally 5 weeks after insufflation. Beside tumor growth, immunologic changes (peripheral leukocyte subpopulations, plasma levels of TNFalpha and IL-10) were evaluated during the perioperative course in all animals. RESULTS: Subcutaneous tumor growth was promoted by the CO2 (99 +/- 55 mg; p < 0.01) compared to the helium (40 +/- 41 mg) and control groups (36 +/- 33 mg). Total intraperitoneal tumor weight was 718 +/- 690 mg in the CO2 group compared to the helium (549 +/- 233 mg) and control groups (521 +/- 221 mg). While peripheral leukocyte subpopulations only differed between the laparoscopic groups and the control group during the perioperative course, TNFalpha plasma levels were significantly decreased and IL-10 plasma levels significantly increased in the CO2 group compared to the helium and control groups in the postoperative course. CONCLUSION: The insufflation of CO2 promotes tumor growth compared to the helium and control groups in a rat model. In addition, increased tumor growth was associated with a significant increase in IL-10 and a decrease in TNFalpha plasma levels.

Adenocarcinoma↗

K-ras mutations in stools and tissue samples from patients with malignant and nonmalignant pancreatic diseases.

Mutant-enriched PCR and reverse dot blot hybridization in microplates were applied for examining K-ras status in stools and tissue samples from patients with pancreatic tumors and chronic pancreatitis. In tissue samples, K-ras mutations were found in 32 of 35 cases of ductal adenocarcinoma, in 5 of 7 periampullary cancers, in 1 cystadenocarcinoma, and in 3 of 5 patients with chronic pancreatitis. In stools, mutated K-ras was seen in 10 of 25 cases of ductal adenocarcinoma, in 1 case of cystadenocarcinoma, and in 2 of 6 cases of chronic pancreatitis. These data indicate that the K-ras status of stool samples may help identify pancreatic carcinoma and persons at risk for cancer development; however, it does not allow discrimination of malignant from nonmalignant diseases.

Adenocarcinoma↗

[Peritoneal instillation of taurolidine and heparin for preventing intraperitoneal tumor growth and trocar metastases in laparoscopic operations in the rat model].

BACKGROUND: Although port-site metastases occur after laparoscopic surgery, there is no generally accepted approach to prevent tumor implantation so far. METHODS: In order to prevent tumor metastases, the effect of taurolidine and heparin on the growth of colon adenocarcinoma DHD/K12/TRb was measured in vitro and in a rat model. After incubation of the cells with heparin, taurolidine or both substances, the cell kinetics were determined. In a second experiment, tumor cells were administered intraperitoneally in rats (n = 60) and pneumoperitoneum was established over 30 min. Rats were randomized into four groups (I: tumor cells; II: cells + heparin; III: cells + taurolidine; IV: cells + taurolidine + heparin). RESULTS: While tumor cell growth was not influenced by heparin in vitro, growth decreased significantly after incubation with taurolidine and taurolidine/heparin. In vivo, intraperitoneal tumor weight was lower in rats receiving heparin (298 +/- 155 mg) and taurolidine (149 +/- 247 mg) than in the control group (596 +/- 278 mg). When the two substance were combined, tumor growth was even less (21.5 +/- 36 mg). Trocar metastases were only lower in rats receiving taurolidine or the combination of taurolidine and heparin. CONCLUSION: In vivo, heparin inhibits intraperitoneal tumor growth only slightly, while taurolidine causes a significant decrease in tumor cell growth in vitro as well as intraperitoneal tumor growth and trocar metastases in vivo.

Adenocarcinoma↗

Different motor actions of dynorphins and nonpeptide kappa opioid receptor agonists in the isolated rat colon.

Dynorphin 1-17 has been suggested to be the endogenous ligand for kappa opioid receptors. In this study motor effects of dynorphin 1-17, its N-terminal fragments d-Pen2,d-Pen5-enkephalin (DPDPE) and d-Ser2-[Leu5]enkephalin-Thr (DSLET) without or with pretreatment with naloxone, (-)-2-(furylmethyl)-noretacocine (Mr 2266) or tetrodotoxin (TTX) on the isolated rat colon were compared with those of nonpeptide kappa opioid receptor agonists. Intraluminal pressure changes were measured by perfusion manometry in preparations maintained in a standard organ bath. Dynorphin 1-17, 1-9, 1-8, 1-6, [Leu5]enkephalin, DPDPE and DSLET dose dependently stimulated the tone in the proximal, middle and distal colon with the maximum response at 10(-6) to 10(-5) M. The stimulation produced by Tyr-Gly-Gly-Phe and Tyr-Gly-Gly was 60 and 600 times less potent, respectively. Concentrations of 10(-10) to 10(-6) M des-Tyr1-[Leu5]enkephalin, dynorphin 3-13, 6-17, 1-methyl-2-(3-thienylcarbonyl)-amino-ethyl-5-(2-fluorophenyl)-H-2,3 dihydro-1,4-benzodiazepine, trans-(+/-)-3,4-dichloro-N-methyl-N-(2-(1-pyrrolidinyl) cyclohexyl)-benzene- acetamide-methane sulfonate and (5a,7a,8B)-(-)-N-methyl-(7-(1-pyrrolidinyl)-1-oxaspiro(4,5)-dec-8- yl) benzeneacet-amide produced no changes in motor activity of the rat colon. Only doses exceeding 10(-6) M of the latter three substances stimulated colonic tone. This action was inhibited neither by naloxone nor by Mr 2266. In contrast, the stimulation by dynorphin 1-17 and 1-6 was inhibited to a greater extent by naloxone than by Mr 2266.(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

Immediate diagnosis in vaginal cytology using interference contrast microscopy (Nomarski).

Studying fresh aspiration material from the posterior fornix and cervix, by Interference Contrast Microscopy (Nomarski) is a good method of cytologic examination. It is shown how most cell types can be observed, just as they can be by the classical Papanicolaou staining. Normal and abnormal, even dysplastic and malignant cells can be recognized. This method is also very useful for identifying parasites, fungi and bacteria, by morphology and active movements. While encoraging the use of this method, it is advisable to compare the results with slides examined later by the Papanicolaou technique, for maximum safety of the patient.

Bacteria↗