Biomedical subjects

M Nagelschmidt

Publications and source records attributed to M Nagelschmidt.

At least 19 recordsLinked to original sources

PubMed2005

Local administration of TGF-beta1 to reinforce the anterior abdominal wall in a rat model of incisional hernia.

The purpose of this study was to investigate different forms of the local application of TGF-beta(1) for augmentation of the anterior abdominal wall in an appropriate model of an incisional hernia. Sixty male Sprague-Dawley rats were divided into six groups. Artificial defects of the anterior abdominal wall were closed with one of the following methods: running Prolene suture, Vicryl mesh, prolene suture followed by an intramuscular injection of 1 mug TGF-beta(1), Vicryl mesh coated with 1 mug TGF-beta(1), and prolene suture coated with 1 mug TGF-beta(1). A control group did not receive any defect and treatment. Six weeks after operation, tensile strength, collagen content, gene expression of collagen I and III, blood vessels, and thickness of collagen fibres were evaluated. Tensile strength was strongest in the controls (14.2 (10.5-18 N)). There was no increase in tensile strength due to the administration of TGF-beta(1). On the contrary, bolus injection of the growth factor resulted in a significantly decreased strength of the wound tissue when compared to the groups 1, 4, 5, and 6 (9.1 (4.2-9.1 N)). These results correlated with the gene expression of collagen I and III. Local application of TGF-beta(1) did not augment the strength of the abdominal wall after 6 weeks.

Abdominal Wall↗

PubMed2004

[The technique of laparoscopic-thoracoscopic esophageal resection for esophageal cancer--first experiences].

Esophageal resection for carcinoma is still associated with high mortality and morbidity. Minimally invasive techniques are regarded to reduce operative trauma. However, to date only few studies on minimally invasive esophageal resection have been published. We describe in detail the technique of combined laparoscopic and thoracoscopic esophageal resection with gastric-pull-up and conventional open cervical anastomosis for esophageal squamous carcinoma. Prone positioning of the patient with bilateral lung ventilation was used during the thoracoscopic part of the operation. Our first experiences in 5 patients confirm the feasibility of the technique. We did not observe any surgical related adverse incidences and found the typically advantages of minimally invasive surgery, such as early mobility, less pain and a comfortable cosmetic result in our patients. Although the number of procedures is to low to decide the value of minimally invasive surgery for esophageal cancer, we think it could be a promising technology to reduce mortality and morbidity for esophageal resection.

Carcinoma, Squamous Cell↗

PubMed2001

The impact of gas laparoscopy on abdominal plasminogen activator activity.

BACKGROUND: The impairment of intestinal perfusion following induction of a pneumoperitoneum may lead to a reduction of peritoneal tissue plasminogen activator (tPA) activity and a concomitant increased risk of adhesion formation. METHODS: Pigs were laparotomized to take peritoneal biopsy specimens from the cecum, the ileum, and the abdominal wall. A 15 mmHg pneumoperitoneum was established for 3 h by the insufflation of carbon dioxide (group 2, n = 6) or helium (group 3, n = 6). Group 1 (n = 7) received no gas insufflation. After a 2-h recovery period, additional tissue samples were harvested. Specific tPA activity was then determined in the tissue extracts. RESULTS: During surgery, specific tPA activity decreased in all the samples. As compared with the control group (100%), this reduction was strongly aggravated in the cecum (-67.6%, p < 0.05) and the ileum (-70.8%) of the CO2 group but only slightly aggravated in the helium group. The parietal peritoneum was not specifically affected by gas insufflation. CONCLUSION: The use of a pneumoperitoneum with carbon dioxide significantly affects peritoneal tPA activity and thus may represent a stimulus for adhesion formation.

Animals↗

PubMed2001

Extension of ischemic tolerance of porcine livers by cold preservation including postconditioning with gaseous oxygen.

BACKGROUND: Transplantation of organs from nonheartbeating donors was recommended to reduce organ shortage. In vitro experiments with rat livers have shown that the warm ischemic tolerance of the liver may be extended by persufflation with gaseous oxygen during cold storage. The qualification of this method for procurement of livers harvested after cardiac arrest was tested in an in vivo approach with pigs. METHODS: Livers from 15 donor pigs were explanted, heparinized, flushed with and stored in University of Wisconsin solution for 4 hr at 4 degrees C, and then implanted into 15 recipients. The organs were dissected immediately after cardiac arrest (group 1) or after 60 min of warm ischemia (groups 2 and 3). Group 2 livers received 75,000 IU of superoxide dismutase together with the flush solution and were persufflated with gaseous oxygen via the venous vascular system during cold storage. Main end point was survival after 5 days. Additionally, metabolic, functional and inflammatory criteria were measured in the blood. RESULTS: All animals of the groups 1 and 2 survived, all animals of group 3 died within 3 hr after reperfusion. In all groups the blood parameters reflected significant damage of the livers. However, the ischemic damage was comparable in the groups 1 and 2 whereas the livers of group 3 exhibited significantly higher levels of aspartate alanine aminotransferase and lactate dehydrogenase, and a significantly elongated partial thromboplastin time 1 hr after reperfusion (P=0.016). CONCLUSIONS: Venous systemic oxygen persufflation in combination with antioxidative medication is a promising new method of resuscitating ischemically altered livers from nonheartbeating donors for successful transplantation.

Animals↗

PubMed2001

A pig hemorrhagic shock model: oxygen debt and metabolic acidemia as indicators of severity.

"Uncontrolled bleeding," "a controlled prefixed bleeding volume," or "controlled decrements in blood pressure" are traditional models of experimental hemorrhagic shock. They are influenced by compensatory mechanisms and do not adequately reflect the severity of the cellular insult as a major target for therapeutic strategies. The aim of this study was to develop an animal model that uses oxygen debt (OD) and metabolic acidemia as indicators of hemorrhage severity. Twenty-five female pigs (mean weight: 23.8 kg) were anesthesized and randomized to 1 of 5 groups of increasing OD (<50 through >120 mL/kg). The predetermined OD was accrued by hemorrhage uniformly over 60 min and followed by retransfusion. The animals were allowed to recover under anesthesia for 200 min and were then observed for 3 days. The extent of metabolic derangements were quantified by arterial base excess (BE) and plasma lactate (LAC) measurements. OD, BE, and LAC were shown to be superior as predictors of outcome in comparison with traditional variables ("bleeding volume," "blood pressure," "cardiac output") in correlation and regression. Of the analyzed predictors of outcome, BE and LAC showed the highest correlation to levels of OD (r = -0.78, 0.8 respectively; P < 0.0001), and regression models were developed. The LD50 for OD was 95.0 mL/kg, for BE -15.3 mmol/L and for LAC 7.7 mmol/L. By using the developed regression models, it is possible to estimate accurately the actual level of OD from BE and LAC values obtained during hemorrhagic shock. OD, BE, and LAC appear to be optimal indicators of severity for a pig hemorrhagic shock model.

Animals↗

PubMed2000

Evaluation of the effects of a pneumoperitoneum with carbon dioxide or helium in a porcine model of endotoxemia.

BACKGROUND: The expansion of the laparoscopic techniques to the critically ill patient is currently under debate. In order to evaluate the potential risks of performing laparoscopy in a body with signs of sepsis, the effects of the pneumoperitoneum were studied in a porcine model of mild endotoxemia. METHODS: Twenty-eight pigs were separated into four groups of seven animals: untreated control (C), 2 microg/kg/h endotoxin (E), endotoxin and a pneumoperitoneum (3 h, 15 mmHg) with CO2 (EC) or with helium (EH). Hemodynamic and homeostatic variables were studied for a period of 5.5 h. Primary endpoints were arterial and mucosal pH and the ATP content of the bowel wall. Statistical evaluation was performed using analysis of variance and the Bonferroni test. RESULTS: Endotoxin infusion induced characteristic symptoms of early sepsis: increase of arterial CO2, pulmonary arterial, portal venous, and pulmonary artery wedge pressure, and decrease of arterial pressure, cardiac output, arterial and mucosal pH. An additional pneumoperitoneum led to aggravation of all criteria with significant alterations in arterial and mucosal pH, arterial CO2, wedge and portal venous pressure. The most striking derangement of mean values was observed for mucosal pH (EC: 7.40, EH: 7.54) and arterial pH (EC: 7.15, EH: 7.18). In group EC, two animals died in septic shock. CONCLUSION: Applying a pneumoperitoneum during an ongoing sepsis significantly deteriorates hemodynamic and homeostatic variables, thus enhancing the risk of severe complications.

Adenosine Triphosphate↗

PubMed2000

The clinical impact of warmed insufflation carbon dioxide gas for laparoscopic cholecystectomy.

BACKGROUND: Reports suggest that the insufflation of cold gas to produce a pneumoperitoneum for laparoscopic surgery can lead to an intraoperative decrease in core body temperature and increased postoperative pain. METHODS: In a randomized controlled trial with 20 patients undergoing laparoscopic cholecystectomy, the effect of insufflation using carbon dioxide gas warmed to 37 degrees C (group W) was compared with insufflation using room-temperature cold (21 degrees C) gas (group C). Intraoperative body core and intra-abdominal temperatures were determined at the beginning and end of surgery. Postoperative pain intensity was evaluated using a visual analog scale and recording the consumption of analgesics. RESULTS: There were no significant group-specific differences during the operation, neither in body temperature (group W: 36.1 +/- 0.4 degrees C vs group C: 35.7 +/- 0.6 degrees C) nor in intra-abdominal temperature (group W: 35.9 +/- 0.3 degrees C vs group C: 35.6 +/- 0. 6 degrees C). Postoperatively, the two groups did not differ in pain susceptibility and need of analgesics. CONCLUSION: The use of carbon dioxide gas warmed to body temperature to produce a pneumoperitoneum during short-term laparoscopic surgery has no clinically important effect.

Aged↗

PubMed2000

Negative side-effects of retention sutures for abdominal wound closure. A prospective randomised study.

OBJECTIVE: To assess the effect of retention sutures on the postoperative course of patients after major abdominal operations. DESIGN: Prospective, randomised study. SETTING: Teaching hospital, Germany. SUBJECTS: 95 patients who were at increased risk of wound failure after major abdominal operations. INTERVENTION: Conventional mass closure either with (n = 44) or without (n = 51) reinforcement by wire retention sutures. MAIN OUTCOME MEASURES: Pain intensity on postoperative days 3, 6, 9, and 12, patients' acceptance, retention-suture-related morbidity, general morbidity. RESULTS: Postoperative pain was overall more severe with retention sutures. On day 6, 31/49 control patients but only 13/41 patients with retention sutures were pain-free (p = 0.003, 95% CI 0.12 to 0.51). Twelve of 44 patients with retention sutures developed local complications of the sutures, and 21 of the 44 had to have them removed prematurely, in most cases because of intolerable pain. CONCLUSIONS: Retention sutures used to close abdominal wounds cause inconvenience, pain, and specific morbidity.

Abdominal Muscles↗

PubMed2000

Plasma concentration of biologically active fibronectin and fibronectin bound to gelatin-like material in a porcine model of hyperdynamic endotoxic shock.

Due to its opsonizing role, plasma fibronectin (pFN) binds to circulating degradation products deriving from collagenous structures and mediates their elimination by the reticuloendothelial system (RES). In septic shock, an overflow of this material may lead to a lack of pFN and an impaired RES activity. In fact, low pFN levels have been reported to correlate with unfavorable clinical outcome. However, dysfunction of the RES is also caused by other shock related factors, and death from septic shock also has been observed in the presence of normal FN levels. To investigate the involvement of opsonic FN in the progression of sepsis, we discriminated between biologically active FN and FN bound to gelatin-like material in pigs developing a hyperdynamic endotoxic shock. All FN determinations were performed with the immunochemical assay. Discrimination between free FN and complexed FN was achieved by separation on gelatin sepharose. A continuous decrease of total FN and free FN was observed in the septic group reaching 57% and 50% of the initial level at the end of the 5-h observation period, respectively. However, a significant difference was not detected before both the microcirculatory and macrocirculatory alterations indicative of hyperdynamic endotoxic shock were completely established. Complexed FN was increased slightly in both groups without any group specific differences. We conclude that the FN-mediated opsonization of circulating gelatine-like material does not play a critical role in early circulatory shock.

Animals↗

PubMed2000

Risks and benefits of preoperative high dose methylprednisolone in surgical patients: a systematic review.

BACKGROUND: A single preoperative high dose of methylprednisolone (15 to 30 mg/kg) has been advocated in surgery, because it may inhibit the surgical stress response and thereby improve postoperative outcome and convalescence. However, these potential clinical benefits must be weighed against possible adverse effects. OBJECTIVE: To conduct a risk-benefit analysis using a meta-analysis, to compare complication rates and clinical advantages associated with the use of high dose methylprednisolone in surgical patients. METHODS: Randomised controlled trials of high dose methylprednisolone in elective and trauma surgery were systematically searched for in various literature databases. Outcome data on adverse effects, postoperative pain and hospital stay were extracted and statistically pooled in fixed-effects meta-analyses. RESULTS: We located 51 studies in elective cardiac and noncardiac surgery, as well as traumatology. Pooled data failed to show any significant increase in complication rates. In patients treated with corticosteroids, nonsignificantly more gastrointestinal bleeding and wound complications were observed; the 95% confidence interval boundaries of the numbers-needed-to-harm were 59 and 38, respectively. The only significant finding was a reduction of pulmonary complications (risk difference -3.5%; 95% confidence interval -1.0 to -6.1), mainly in trauma patients. CONCLUSION: For patients undergoing surgical procedures, a perioperative single-shot administration of high dose methylprednisolone is not associated with a significant increase in the incidence of adverse effects. In patients with multiple fractures, limited evidence suggests promising benefits of glucocorticoids on pulmonary complications.

Animals↗

PubMed1999

CO(2) pneumoperitoneum: what we know and what we need to know.

The development of the laparoscopic technique in surgery was so overwhelming that scientific evaluation could not keep in step. While investigators were still discussing the effects of the pneumoperitoneum on the healthy organism, laparoscopy was already performed in patients with an acute abdomen due to trauma or disease. Therefore, there is an urgent need of further experimental and clinical studies with relevant endpoints to gain external evidence concerning the benefits of diagnostic or therapeutic laparoscopy for critically ill patients. In experiments with pigs we have shown that even in a healthy organism perfusion and energy metabolism of the small bowel is impaired by a pneumoperitoneum with carbon dioxide. Under the conditions of a systemic inflammatory response syndrome induced by infusion of endotoxin, the negative effects of the pneumoperitoneum were significantly amplified. Furthermore, we found that the increased intracranial pressure as caused by a head injury was further enhanced during a pneumoperitoneum but not by the alternative method of mechanical wall retraction. The current literature dealing with the effects of a pneumoperitoneum in critically ill patients is still controversial. Our data support the results of those authors who hold the opinion that creating a pneumoperitoneum in patients with acute abdominal problems means an additional serious burden that in single cases may lead to a disaster. As evidence is lacking, the current extension of laparoscopy into the field of intensive care medicine is still a human experiment that must be performed with high responsibility, extensive monitoring, and according to the rules of a clinical study.

Abdomen, Acute↗

PubMed1999

Endoscopic use of fibrin adhesives: problems when injecting through long catheters.

When used endoscopically fibrin adhesives are injected through twin-lumen catheters, which can reach up to 180 cm in length. Because fibrinogen solutions have a high viscosity, significant delivery forces are necessary, resulting in discomfort for the operator. Therefore, the two predominant fibrin sealants were characterized with respect to their viscosity and the force needed for their injection. Viscosity was determined at 18 degrees C, 25 degrees C, and 37 degrees C in a micro-Ostwald viscosimeter. Additionally, the maximum forces needed for injection through a 27-cm and a 160-cm catheter were determined at 25 degrees C in an Instron materials testing machine. Compared with preparation A the viscosity of preparation B was 8.0-34.5 times higher at 18 degrees C, 4.6-13.8 times higher at 25 degrees C and 3.1-6.4 times higher at 37 degrees C. In consequence, the delivery forces were 1.5-2.5 times (27 cm probe) and 3.4-4.5 times (160 cm probe) the values determined for preparation A. For preparation B a maximum load of 3.8 kg was necessary for injection. Assuming that different adhesive preparations have the same effect, a preparation of lower viscosity seems to be more suitable for use via long catheters than a preparation of high viscosity.

Catheterization, Peripheral↗

PubMed1999

Preoperative high dose methylprednisolone improves patients outcome after abdominal surgery.

OBJECTIVE: To assess the effect of preoperative high dose methylprednisolone on stress response and outcome. DESIGN: Randomised, placebo-controlled, double-blind study. SETTING: University hospital, Germany. SUBJECTS: 20 patients listed for abdominal surgery of whom 10 had major intra-abdominal interventions and 10 had incisional hernias repaired. INTERVENTIONS: Methylprednisolone 30 mg/kg (100 ml) was given by slow intravenous infusion 90-60 minutes before operation. The control group received the same volume of sodium chloride. MAIN OUTCOME MEASURES: Speed of convalescence, degree of fatigue, amount of pain, consumption of analgesics, breathing capacity, and hospital stay, as well as humoral and cellular mediators of the stress response. RESULTS: Methylprednisolone significantly improved criteria of postoperative recovery, fatigue by 47%, (day 1), convalescence by about 45% (days 1-3), and breathing capacity (FEV1) between 47% and 29% (days 5, 7) (p < 0.05, ANOVA), and led to a significant reduction of median hospital stay of 4.5 days. C-reactive protein concentration was significantly decreased (by 46% on day 3) and T-cell activation was suppressed (day 1). CONCLUSION: Outcome of the patients after conventional abdominal surgery is substantially improved by preoperative high dose methylprednisolone. This effect is more pronounced in patients having major operations.

Adult↗

PubMed1998

Successful transplantation of porcine livers after warm ischemic insult in situ and cold preservation including postconditioning with gaseous oxygen.

BACKGROUND: In order to reduce the shortage of viable donor livers for organ transplantation, a method has been developed that allows even predamaged livers from nonheartbeating donors to be used as transplantable organs. METHODS: Porcine livers were harvested 45 min after cardiac arrest of the nonheparinized donor, preflushed with heparinized saline solution, and subsequently rinsed with University of Wisconsin solution, to which superoxide dismutase was added as an oxygen free radical scavenger. Thereafter, the livers were persufflated with gaseous oxygen via the venous vascular system while immersed in University of Wisconsin solution at 4 degrees C for 4 to 5 hr. RESULTS: After orthotopic transplantation, all of the livers conditioned with gaseous oxygen were able to support life-sustaining function during the whole observation period of 7 days post transplantation, while no survival of the recipients could be obtained without the described treatment. CONCLUSIONS: The present study establishes a new perspective for the use of ischemically altered livers from nonheartbeating donors for organ transplantation under clinical circumstances.

Animals↗

PubMed1998

[Evaluation of qualification regulations for medical faculties of German universities and recommendations for standardization].

The original reason for using the German "Habilitation" degree to mean that a candidade had qualified and could conduct research and teach at a university is no longer really valid, as this is being threatened by its importance to further careers. Medical faculties must discuss how this development can be curtailed. In order to check the current situation, the Habilitation degree systems of 36 medical faculties of German universities were compared with the aid of a scoring system. They differed dramatically. Conformity existed only in the demand for a doctoral dissertation, scientific publications and a lecture on approval. Concerning other criteria for qualification there was decreasing consensus in the following order: Habilitation thesis, commitment to teaching, further professional education, participation in congresses, inaugural lecture, qualification to teach, scientific activity, broad background in the discipline, and introduction to the faculty. Application of the scoring system with a maximum of 33 score points resulted in a mean value of 15.2 points and a range from 6 to 29 points. A significant decrease in the score values occurred with increasing age of the Habilitation degree (P = 0.002). Even if scoring systems are ambiguous and unfair, our analysis revealed serious differences in the quality of the Habilitation degree. Presuming that the German Habilitation degree should be maintained as a high-level qualification, we developed proposals that might be used to standardize this academic examination.

Curriculum↗

PubMed1998

Endischemic oxygen persufflation to improve viability of marginally preserved donor livers.

The quality of cold-stored donor livers slowly declines beyond approximately 12 h, although these organs may still be used for clinical transplantation. The aim of the present study was to improve the energetic status and viability of long-term-preserved livers by short-term gaseous oxygen insufflation prior to implantation of the organ using a technique that has already been shown to promote aerobic energy metabolism during hypothermia. Livers from ten male Wistar rats were isolated, rinsed blood-free. Five livers (group 1) were stored for 48 h at 4 degrees C in UW preservation solution, and five livers (group 2) were isolated and stored in the same manner for 47 h, and were then, during the last 60 min of the preservation period, connected to a persufflation device and gaseous oxygen was introduced into the organ via the inferior caval vein, with the liver still immersed in cold UW solution. This technique of endischemic gaseous oxygenation resulted in a significant normalization of vascular resistance upon isolated reperfusion in vitro and a reduction in hepatic efflux of alanine aminotransferase as well as glutamate dehydrogenase, which led to improved recovery of the reperfused grafts of group 2 as evidenced by an elevated energy charge potential at the end of the reperfusion period. In conclusion, the technique described seemed effective in enhancing the preoperative viability of marginal donor grafts.

Animals↗

PubMed1998

Polyethylene glycol 4000 attenuates adhesion formation in rats by suppression of peritoneal inflammation and collagen incorporation.

BACKGROUND: Postoperative separation of the peritoneal surfaces is a promising approach for the prevention of adhesion formation. Instillation of polyethylene glycol 4000 (PEG) was recommended as an appropriate method. METHODS: In a time-course study in rats, efficacy and mode of action of PEG was investigated. Adhesions were induced by crushing of the cecum. Sixty animals were randomly allocated to three control groups with intraperitoneal instillation of 5 mL 0.9% NaCl and to three therapy groups treated with 5 mL 20% PEG. After 3, 7, and 21 days, adhesion grade, intraperitoneal leukocytes, and collagen incorporation into the adhesion strands were evaluated. RESULTS: Administration of PEG resulted in a decrease of leukocytes by 43% (days 3 and 7), a reduction of the adhesion score by 85% (day 3), 77% (day 7), and 79% (day 21), and an impairment of collagen deposition by 54% (day 7) and 44% (day 21). CONCLUSIONS: Coating the peritoneal surfaces with PEG is a highly effective measure to suppress the fatal sequence of posttraumatic inflammation, formation of initial adhesions, and their subsequent organization to strong permanent adhesion strands.

Administration, Topical↗

PubMed1998

[Effect of pneumoperitoneum on plasminogen activator activity in the abdomen].

In a study in pigs it was examined whether peritoneal plasminogen activator activity (PAA) is impaired by creation of a pneumoperitoneum (PP) with CO2 or with helium. The animals were anesthetised and laparotomised, and peritoneal biopsies were taken from the cecum, the ileum and the wound site. Then a PP of 15 mmHg was created with CO2 (Grp. 1, n = 6) or helium (Grp. 2, n = 6). Group 0 (n = 7) was left without gas insufflation. After a PP of 3 hrs and an additional observation period of 2 hrs further tissue samples were collected. In the biopsies specific PAA was determined. In all groups a decrease of specific PAA occurred. However, at the end of the experiment PAA was significantly lower in the cecum of the CO2-group (24.3 U/mg, 32.4%) when compared to the controls without gas (75.1 U/mg, 100%) or the helium group (65.1 U/mg 86.7%). Our data raise suspicion that insufflation of CO2 for laparoscopic intervention may enhance the risk of peritoneal adhesions by a suppression of PAA.

Animals↗