Laparoscopy. To inflate or lift?
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Animals↗
Biomedical subjects
S Köster
Publications and source records attributed to S Köster.
The influence of pneumoperitoneum used in laparoscopic surgery on an intraabdominal tumor growth.
BACKGROUND: Numerous clinical reports have raised the possibility that laparoscopic cancer surgery has an inherently detrimental effect on tumor growth. The aim of the current study was to examine the influence of a pneumoperitoneum on the morphology of the peritoneum and the intraperitoneal tumor cell implantation and growth in the case of intraabdominal spread of tumor cells. METHODS: Black mice were stratified into 2 groups of 36 animals each. A CO(2) pneumoperitoneum was induced for 30 minutes in Group 1 and 200,000 cells of a malignant melanoma were injected intraperitoneally. In Group 2 only tumor cells were injected. After a defined period of hours, 4 animals were killed and the peritoneum was examined by scanning electron microscopy. RESULTS: In Group 1, starting 2 hours after release of the pneumoperitoneum, strong alterations of the peritoneum became visible and parts of the underlying basal lamina were laid bare. Tumor cells attached to the free basal lamina and formed predominantly diffuse metastases throughout the peritoneum within the next 96 hours. No diffuse changes of the peritoneal surface and no diffuse metastases were observed in the second group. Singular metastases followed gravity and involved the anterior abdominal wall. CONCLUSIONS: Because these findings explain the clinical findings of intraabdominal metastases after laparoscopy the authors conclude that the pneumoperitoneum provokes particular damage to the peritoneum that induces a specific intraperitoneal tumor growth. [See also editorial counterpoint on pages 747-8 and reply to counterpoint on pages 749-50, this issue.
Animals↗
Characteristic alterations of the peritoneum after carbon dioxide pneumoperitoneum.
OBJECTIVE: Any route of entry into the abdomen contributes to alterations of the intraperitoneal organs with different clinical consequences. Characteristic alterations of the peritoneum after CO2 pneumoperitoneum used in laparoscopic surgery is examined. METHODS: A CO2 pneumoperitoneum with an intraperitoneal pressure of 6 mmHg was applied for 30 min in 32 nude mice. In the course of 4 days, the animals were killed and the peritoneal surface of the abdominal wall was studied by means of scanning electron microscopy. RESULTS: Already 2 h after release of the pneumoperitoneum, mesothelial cells were bulging up. The intercellular clefts thereby increased in size, and the underlying basal lamina became visible. This reaction peaked after 12 h. Subsequently, peritoneal macrophages and lymphocytes filled all gaps, thereby recovering the basal lamina. CONCLUSION: The morphologic integrity of the peritoneum is temporarily disturbed by a CO2 pneumoperitoneum.
Animals↗
Selective substrates for non-neuronal monoamine transporters.
The recently identified transport proteins organic cation transporter 1 (OCT1), OCT2, and extraneuronal monoamine transporter (EMT) accept dopamine, noradrenaline, adrenaline, and 5-hydroxytryptamine as substrates and hence qualify as non-neuronal monoamine transporters. In the present study, selective transport substrates were identified that allow, by analogy to receptor agonists, functional discrimination of these transporters. To contrast efficiency of solute transport, stably transfected 293 cell lines, each expressing a single transporter, were examined side by side in uptake experiments with radiolabeled substrates. Normalized uptake rates indicate that tetraethylammonium, with a rate of about 0.5 relative to 1-methyl-4-phenylpyridinium (MPP+), is a good substrate for OCT1 and OCT2. It was not, however, accepted as substrate by EMT. Choline was transported exclusively by OCT1, with a rate of about 0.5 relative to MPP+. Histamine was a good substrate with a rate of about 0.6 relative to MPP+ for OCT2 and EMT, but was not transported by OCT1. Guanidine was an excellent substrate for OCT2, with a rate as high as that of MPP+. Transport of guanidine by OCT1 was low, and transport by EMT was negligible. With the guanidine derivatives cimetidine and creatinine, a pattern strikingly similar to guanidine was observed. Collectively, these substrates reveal key differences in solute recognition and turnover and thus challenge the concept of "polyspecific" organic cation transporters. In addition, our data, when compared with previous studies, suggest that OCT2 corresponds to the organic cation/H+ antiport mechanism in renal brush-border membrane vesicles, and that EMT corresponds to the guanidine/H+ antiport mechanism in membrane vesicles from placenta and intestine.
Amino Acid Sequence↗
[A scanning microscopy study of the peritoneum in mice after application of a CO2-pneumoperitoneum].
OBJECTIVE: The application of a CO2-pneumoperitoneum in operative laparoscopy presumably leads to basic alterations of the intraperitoneal homeostasis. In order to better understand the pathophysiology of this phenomenon, the morphologic alterations of the mesothelium after CO2-application will be examined. MATERIAL AND METHODS: In 36 mice (C 57, black mice) a CO2-pneumoperitoneum with an intraperitoneal pressure of 6 mm Hg was applied for 30 minutes. After 1, 2, 6, 12, 24, 48, 72 and 96 hours each of 4 animals were killed and the entire peritoneum was examined by scanning electron microscopy. RESULTS: Already after 1 hour mesothelial cells became cuboidal, were detached and showed condensation. After 2 hours this initial reaction reached its peak; immature cells then attached to the free basal membrane. After 96 hours the entire mesothelium was regenerated. CONCLUSIONS: The morphologic integrity of the mesothelium is temporarily disturbed by a CO2-pneumoperitoneum. Reasons for this phenomenon may be either the abdominal pressure or a CO2-induced surface acidosis. In further studies, the influence of the described phenomena on intraperitoneal formation of metastases will be examined.
Animals↗
Anti-pterins as tools to characterize the function of tetrahydrobiopterin in NO synthase.
Nitric oxide synthases (NOS) are homodimeric enzymes that NADPH-dependently convert L-arginine to nitric oxide and L-citrulline. Interestingly, all NOS also require (6R)-5,6,7, 8-tetrahydro-L-biopterin (H4Bip) for maximal activity although the mechanism is not fully understood. Basal NOS activity, i.e. that in the absence of exogenous H4Bip, has been attributed to enzyme-associated H4Bip. To elucidate further H4Bip function in purified NOS, we developed two types of pterin-based NOS inhibitors, termed anti-pterins. In contrast to type II anti-pterins, type I anti-pterins specifically displaced enzyme-associated H4Bip and inhibited H4Bip-stimulated NOS activity in a fully competitive manner but, surprisingly, had no effect on basal NOS activity. Moreover, for a number of different NOS preparations basal activity (percent of Vmax) was frequently higher than the percentage of pterin saturation and was not affected by preincubation of enzyme with H4Bip. Thus, basal NOS activity appeared to be independent of enzyme-associated H4Bip. The lack of intrinsic 4a-pterincarbinolamine dehydratase activity argued against classical H4Bip redox cycling in NOS. Rather, H4Bip was required for both maximal activity and stability of NOS by binding to the oxygenase/dimerization domain and preventing monomerization and inactivation during L-arginine turnover. Since anti-pterins were also effective in intact cells, they may become useful in modulating states of pathologically high nitric oxide formation.
Animals↗
Transport of monoamine transmitters by the organic cation transporter type 2, OCT2.
The recently cloned apical renal transport system for organic cations (OCT2) exists in dopamine-rich tissues such as kidney and some brain areas (Gründemann, D., Babin-Ebell, J., Martel, F., Ording, N., Schmidt, A., and Schömig, E. (1997) J. Biol. Chem. 272, 10408-10413). The study at hand was performed to answer the question of whether OCT2 accepts dopamine and other monoamine transmitters as substrate. 293 cells were stably transfected with the OCT2r cDNA resulting in the 293OCT2r cell line. Expression of OCT2r in 293 cells induces specific transport of tritiated dopamine, noradrenaline, adrenaline, and 5-hydroxytryptamine (5-HT). Initial rates of specific 3H-dopamine, 3H-noradrenaline, 3H-adrenaline, and 3H-5-HT transport were saturable, the Km values being 2.1, 4.4, 1.9, and 3.6 mmol/liter. The corresponding Vmax values were 3.9, 1.0, 0. 59, and 2.5 nmol min-1.mg of protein-1, respectively. 1, 1'-diisopropyl-2,4'-cyanine (disprocynium24), a known inhibitor of OCT2 with a potent eukaliuric diuretic activity, inhibited 3H-dopamine uptake into 293OCT2r cells with an Ki of 5.1 (2.6, 9.9) nmol/liter. In situ hybridization reveals that, within the kidney, the OCT2r mRNA is restricted to the outer medulla and deep portions of the medullary rays indicating selective expression in the S3 segment of the proximal tubule. These findings open the possibility that OCT2r plays a role in renal dopamine handling.
Animals↗
Laparoscopic surgery: the effects of insufflation gas on tumor-induced lethality in nude mice.
OBJECTIVE: The aim of the study was to examine the effect of helium (group 2), carbon dioxide (group 3), and heated carbon dioxide (group 4) pneumoperitoneum on survival in case of intraabdominal spread of tumor cells in nude mice. STUDY DESIGN: The pneumoperitoneum was induced by a microhysteroflator with an intraperitoneal pressure of 8 mm Hg for 30 minutes. A washed tumor solution (0.4 ml) of a mesothelioma was injected intraperitoneally. RESULTS: The survival rate of group 3 was significantly reduced compared with the controls (group 1) and group 4. The latter groups showed similar survival rates. In groups 2 and 3 no significant differences in survival rate were observed. CONCLUSION: Clinical observations and the results of this animal study warn against the use of standard unheated carbon dioxide pneumoperitoneum in case of malignant tumors. Heated carbon dioxide seems to be advantageous.
Animals↗
Pterin-4a-carbinolamine dehydratase from Pseudomonas aeruginosa: characterization, catalytic mechanism and comparison to the human enzyme.
The three-dimensional structure of pterin-4a-carbinolamine dehydratase (PCD) from Pseudomonas aeruginosa has been solved. Based on this we have investigated the roles of putative active center residues through functional replacement by site-directed mutagenesis. Three histidines, His73, His74 and His91, appear to be involved in dehydration catalysis. The three-dimensional positions of these residues match those of corresponding histidines at the active center of human PCD. Based on the coincidence of catalytic parameters, and on the similar effects induced by the mutations, it is concluded that the substrate binding mode and the reaction mechanisms of bacterial and human PCD are basically identical.
Amino Acid Sequence↗
Location of the active site and proposed catalytic mechanism of pterin-4a-carbinolamine dehydratase.
Based on the recently solved three-dimensional structure of pterin-4a-carbinolamine dehydratase from rat/human liver the involvement of the proposed active-site residues Glu57, Asp60, His61, His62, Tyr69, His79, Arg87 and Asp88 was examined by site-directed mutagenesis. Most of the mutants showed reduced activity, and only the Glu57-->Ala mutant and the His61-->Ala, His62-->Ala double mutant were fully devoid of activity. The dissociation constants of quinonoid 6,6-dimethyl-7,8-dihydropterin were significantly increased for binding to the Glu57-->Ala, His61-->Ala, His62-->Ala single mutants and the His61-->Ala, His62-->Ala double mutant, confirming that His61 and His62 are essential for substrate binding and catalysis. The mechanism of dehydration is proposed to involve base catalysis at the N(5)-H group of the substrate by His61.
Amino Acid Sequence↗
Pathophysiologic features of a pneumoperitoneum at laparoscopy: a swine model.
OBJECTIVE: The aim of this study was to examine local and systemic reactions of the body to a pneumoperitoneum to elucidate potential dangers and risks of laparoscopic procedures. STUDY DESIGN: Laparoscopy was performed on 25 pigs. The pigs were divided into five groups by level of intraabdominal pressure (14 and 18 mm Hg) and gas used (carbon dioxide and air). The effects of the pneumoperitoneum on cardiopulmonary condition and the peritoneal milieu were observed. These effects should be the result of various changes as the mechanical, ventilatory, cellular, hormonal, and immunologic levels. RESULTS: In this animal study marked changes in the peritoneal milieu were observed, and we demonstrated that these changes were dependent on the gas used, intraabdominal pressure, and duration of application. Locally these changes are manifest in the development of severe peritoneal acidosis, hypercapnia, and the release of various mediators. Systemic changes, in particular cardiopulmonary changes, also depend on the intraabdominal pressure and the gas used. CONCLUSION: During conventional pneumoperitoneum the peritoneum might change to a large extent so that the development of new risks are possibly encouraged. A reduction in intraabdominal pressure with the use of carbon dioxide as the insufflation gas should result in normal acid-base balance.
Abdomen↗
[Effect of CO2 pneumoperitoneum on intraperitoneal tumor growth in the animal model].
Clinical observations during recent years describe the increased occurrence of rapid intraperitoneal metastases and an impairment of prognosis if a malignant tumour was operated laparoscopically. It is not known whether the observed induction of intraabdominal metastases after laparoscopic surgery in the result of an inadequate surgical procedure with spillage of tumour cells into the abdominal cavity or whether pneumoperitoneum-induced changes of the peritoneal milieu promote tumour growth. An animal model was established to examine the effect of a CO2-pneumoperitoneum on the intraperitoneal growth of tumour cells. Six week old nude mice were divided into 4 groups of 15 animals each. A CO2-pneumoperitoneum was induced by a micro-hysteroflator with an intraperitoneal pressure of 6 mmHg for 90 minutes in groups 2 and 4. Two different tumour cell lines, suspended in 2 ml of Ringer's solution for homogeneous spread of the cells, were injected i.p.. The control groups 1 and 3 received the tumour cells without pneumoperitoneum induction of a CO2-pneumoperitoneum resulted in an increasing seeding rate of tumour cells and provoked a significant increase in the number and size of intraabdominal metastases. Laparoscopic surgery of malignancies is therefore contraindicated.
Animals↗
[Indications for 3 D laparoscopy in gynecology].
In a prospective randomised study we investigated the possibilities of a 3 D-video system in comparison to a 2 D-video system in operative laparoscopy. On 76 patients the following operations were performed: enucleation of fibroids, extirpation of ovarian cysts, fimbrioplasty, tubo-tubal anastomosis and Burch's procedure via preperitoneal access. For microsurgical procedures of the adnexae the new 3 D-technology shows advantages in compared to the standard 2 D-laparoscopy. In these operations the operating area is naturally limited, and hence the disadvantages of the 3 D-technology like limited depth of focus are not important. The 3 D-system allows a very good visualisation even of small structures and safe and exact handling. For surgery of the uterus or larger tumours of the adnexae, the new technology is unsuited.
Equipment Design↗
Human pterin-4 alpha-carbinolamine dehydratase/dimerization cofactor of hepatocyte nuclear factor-1 alpha. Characterization and kinetic analysis of wild-type and mutant enzymes.
Pterin-4a-carbinolamine dehydratase/dimerization cofactor for hepatocyte nuclear factor-1 alpha is a protein with two different functions. We have overexpressed and purified the human wild-type protein, and its Cys81Ser and Cys81Arg mutants. The Cys81Arg mutant has been proposed to be causative in a hyperphenylalaninaemic patient [Citron, B. A., Kaufman, S., Milstien, S., Naylor, E. W., Greene, C. L. & Davis, M. D. (1993) Am. J. Hum. Genet. 53, 768-774]. The dehydratase behaves as a tetramer on gel filtration, while cross-linking experiments showed mono-, di-, tri-, and tetrameric forms, irrespective of the presence of the single Cys81. Sulfhydryl-modifying reagents did not affect the activity, but rather showed that Cys81 is exposed. Various pterins bind and quench the tryptophan fluorescence suggesting the presence of a specific binding site. The fluorescence is destroyed upon light irradiation. Wild-type and the Cys81Ser protein enhance the rate of the phenylalanine hydroxylase assay approximately 10-fold, a value similar to that of native dehydratase from rat liver; the Cys81Arg mutant, in contrast, has significantly lower activity. This is compatible with the hypothesis that the dehydratase is a rate-limiting factor for the in vivo phenylalanine hydroxylase reaction. The three proteins enhance the spontaneous dehydration of the synthetic substrate 6,6-dimethyl-7,8-dihydropterin-4a-carbinolamine approximately 50-70-fold at 4 degrees C and pH 8.5. The results are discussed in view of the recently solved three-dimensional structure of the enzyme [Ficner, R., Sauer, U. W., Stier, G. & Suck, D. (1995) EMBO J. 14, 2032-2042].
Base Sequence↗
[Tumor asepsis in organ saving pelviscopic ovarian surgery exemplified by dermoid cysts].
Three different surgical techniques were performed to remove ovarial tumors by pelviscopic organ-preserving surgery. Contamination of the peritoneal cavity with cystic and tumorous materia had to be prevented. Ovarian surgery was done in 112 pre-menopausal patients. Three techniques were compared: 1. complete extirpation of the cyst, 2. extirpation of the cystic wall after careful irrigation of the cyst, 3. the 'diaphragm technique': the affected ovary is operated inside a bag. Contamination of the peritoneal cavity was prevented only by the 'diaphragm technique'.
Asepsis↗
[Pelviscopic sacropexy in treatment of vaginal prolapse].
Although transabdominal sacropexy to correct vaginal prolapse is technically simple and yields good results, a minimal invasive procedure is desirable in the treatment of this benign condition. We therefore developed a laparoscopic sacropexy technique and were able to apply this operation successfully. Pelviscopic sacropexy does not differ greatly in principle from the intraabdominal approach; however, the techniques used in the individual steps must be adapted to pelviscopic methods.
Female↗
[Pelviscopic ovarian surgery: a new method of safe organ preserving surgery].
For pelviscopic removal of ovarian tumours, a puncture or morcellation of the tumour used to be necessary, frequently causing the peritoneal cavity to be contaminated with contents of cysts or tumourous material. This contamination can be avoided safely by placing the intact tumour into a bag, provided that the tumour has been dissected completely. The intact tumour is put into a bag and both are completely removed at the same time through the abdominal wall. This method increases the safety of pelviscopic ovarian surgery, and its indication for use can be broadened.
Female↗
[Pelviscopic surgery without pneumoperitoneum? A new method and its effects on anesthesia].
New developments in the field of pelviscopic surgery enable us to perform more extensive, time-consuming and difficult operations. Prolonging the increased intraabdominal pressure carries the risk of dangerous complications, especially in high-risk patients. We introduce a new technique to perform prolonged pelviscopic operations without or with only slightly increased intraabdominal pressure. The abdominal wall is suspended from a fixation frame. Negative effects on anaesthesia caused by prolonged increased intraabdominal pressure can be compensated. Many different pelviscopic operations can be performed using this simple and inexpensive technique, particularly in surgical procedures of the adnexae. This new technique is advantageous especially in high-risk patients, who can no longer be excluded from extensive pelviscopic surgery.
Anesthesia, General↗