Influence of hepatocyte growth factor on autologous osteochondral transplants in an animal model.

PURPOSE: Several studies have investigated the influence of different growth factors on hyaline cartilage regeneration. In a rabbit model, hepatocyte growth factor (HGF) was proven to increase the amount of hyaline-like chondrocytes in a mixed fibro-cartilaginous regenerate of small defects. The aim of the current study was to evaluate whether intra-articular administration of HGF influences the ingrowth of osteochondral grafts in a sheep model. TYPE OF STUDY: Animal experiment. METHODS: Both knee joints of eight sheep were opened surgically and osteochondral grafts were harvested and simultaneously transplanted to the opposite condyle of the same joint. The sheep were divided into two groups of four sheep, resulting in 16 grafts per group. In one group, HGF was administered by bilateral intra-articular injections given three times a week for 4 weeks. The control group received isotonic sodium chloride injections. The animals were killed after 3 months. RESULTS: Histological evaluation showed a complete ingrowth of the osseous part of the osteochondral grafts. A healing or ingrowth at the level of the cartilage could not be observed. Histological evaluation of the transplanted grafts according to the modified Mankin score revealed less degeneration in the cartilage of the HGF group, as compared to the control group. In the HGF group, less cloning of chondrocytes and less irregularities of the articular surface were observed. Importantly, no deleterious effects, such as osteophyte formation, cartilage thickening or synovial proliferation, were found. CONCLUSION: HGF positively influenced the cellularity of the transplanted osteochondral graft, but could not diminish the fissures in the marginal zone of the grafts. CLINICAL RELEVANCE: Marginal zone fissures and degeneration in the absence of HGF may undermine long-term results of autologous osteochondral grafts.

[How often is bronchopneumonia overlooked as the cause of death in intensive care unit patients?]. / Wie häufig wird die Bronchopneumonie als Todesursache bei Intensivpatienten übersehen?

BACKGROUND: This study addresses the issue of analyzing the relationship between pre-mortem diagnoses and post-mortem findings in an intensive care unit (ICU). MATERIALS AND METHODS: Investigating a total of 1,205 autopsy cases, pre-mortem and post-mortem diagnoses were retrospectively evaluated and compared statistically by means of established categories (i.e."complete, partial, or lacking concordance" and"clinically suspected diagnosis"). RESULTS: When comparing clinical diagnoses and autopsy findings in terms of bronchopneumonia, concordance was recorded in only 21.15% of the cases investigated. CONCLUSION: In multimorbid ICU patients, bronchopneumonia frequently fails to be clinically recognized since clinical parameters commonly used for monitoring appear to be modified due to therapeutical interventions, and thus are inappropriate to reflect the complete histomorphological equivalent of the disease. This study also emphasizes the importance of autopsy which represents a sensitive means for professional medical quality assurance, and again establishes the necessity for strengthening the request for autopsy, which is currently characterized by an unfavourable decline.

Hyaline cartilage degenerates after autologous osteochondral transplantation.

OBJECTIVES: Autologous osteochondral grafting is a well-established clinical procedure to treat focal cartilage defects in patients, although basic research on this topic remains sparse. The aim of the current study was to evaluate (1) histological changes of transplanted hyaline cartilage of osteochondral grafts and (2) the tissue that connects the transplanted cartilage with the adjacent cartilage in a sheep model. METHOD: Both knee joints of four sheep were opened surgically and osteochondral grafts were harvested and simultaneously transplanted to the contralateral femoral condyle. The animals were sacrificed after three months and the received knee joints were evaluated histologically. RESULTS: Histological evaluation showed a complete ingrowth of the osseous part of the osteochondral grafts. A healing or ingrowth at the level of the cartilage could not be observed. Histological evaluation of the transplanted grafts according to Mankin revealed significantly more and more severe signs of degeneration than the adjacent cartilage, such as cloning of chondrocytes and irregularities of the articular surface. CONCLUSION: We found no connecting tissue between the transplanted and the adjacent cartilage and histological signs of degeneration of the transplanted hyaline cartilage. In the light of these findings, long-term results of autologous osteochondral grafts in human beings have to be followed critically.

Vascular anastomosing by gluing--an experimental study.

BACKGROUND: Performing anastomoses by stitching is very time-consuming. We therefore looked for an alternative technique and used a relatively new surgical adhesive. METHODS: Ten anastomoses between the aorta and a prosthesis were performed on five pigs (Deutsche Landrasse) using surgical glue (BioGlue). The proximal anastomoses between the abdominal aorta and the prostheses were performed end-to-side just below the renal arteries, the distal anastomoses in an end-to-end fashion just above the iliac bifurcation. The aorta between the anastomoses was ligated and resected. The animals were sacrificed between one week and up to four months after operation and anastomoses were analysed by angiography, CT angiography, angioscopy, and histology. RESULTS: Angiography and CT angiography revealed that all anastomoses were patent. No aneurysms were found at the site of anastomoses. No haematomas were detected. Angioscopy revealed well-healed connections between the original aorta and the prosthesis. CONCLUSIONS: We could demonstrate that anastomoses between the aorta and a prosthesis can be performed safely using a surgical adhesive. Further investigations of these anastomoses, especially over the long term, using calcified aortas, are necessary.

Thoracic, but not lumbar, epidural anesthesia improves cardiopulmonary function in ovine pulmonary embolism.

UNLABELLED: We hypothesized that sympathetic stimulation is the main mechanism contributing to hemodynamic failure in pulmonary embolism. We investigated the effects of epidural anesthesia-induced sympathetic blockade, restricted to thoracic and lumbar levels, during pulmonary embolism. Two experiments were performed in chronically instrumented ewes. In the first experiment, six sheep received 6 mL bupivacaine 0.175% (Thoracic Epidural Anesthesia [TEA] group), and six sheep received 6 mL saline 0.9% (TEA-Control group), respectively, via an epidural catheter (T3 level). In the second experiment, six sheep received 2.8 mL bupivacaine 0.375% (Lumbar Epidural Anesthesia [LEA] group), and six sheep received 2.8 mL saline 0.9% (LEA-Control group) epidurally (L4 level). Embolization was performed by IV injection of autologous blood clots (Experiment 1, 0.75 mL/kg; Experiment 2, 0.625 mL/kg). TEA was associated with significantly slower heart rates, decreased mean pulmonary artery pressures and central venous pressures, and significantly higher stroke volume index and oxygenation in comparison with the TEA-Control group. By contrast, LEA was associated with significantly faster heart rates and increased central venous pressures and with a significantly lower stroke volume index in comparison with the LEA-Control group. TEA significantly reduced, and LEA significantly increased, hemodynamic deterioration, suggesting beneficial effects of TEA on cardiopulmonary function during pulmonary thromboembolism. IMPLICATIONS: Thoracic (but not lumbar) epidural anesthesia was associated with beneficial cardiopulmonary effects during experimental pulmonary thromboembolism in sheep.

Successful cardiac transplantation after Novacor implantation in a HIT II-patient using heparin.

The anticoagulative management of patients tested positive for heparin-induced thrombocytopenia type II (HIT II) and requiring cardiac surgery has been difficult until now. A special challenge arises, when left ventricular assist devices have to be implanted for bridging to cardiac transplantation. We report on the anticoagulative management of such a patient, based on the consideration of HIT II-pathophysiology and using heparin for Novacor LVAD implantation and cardiac transplantation.

Does a suitable animal model for research on partial left ventriculectomy exist? Animal models for PLV.

Partial left ventriculectomy is a new surgical option quickly introduced into clinical use worldwide for treating end-stage heart failure in patients with dilated cardiomyopathy. Due to the overwhelming success of this new kind of surgical treatment for dilated cardiomyopathy, experimental research on the physiological and pathophysiological basis was initially not performed. Now, demands for an appropriate animal model have arisen more and more since the outcome of patients treated by partial left ventriculectomy has differed considerably. This review summarizes available experimental models for heart failure in large animals, and discusses their suitability for research on partial left ventriculectomy.

Are patients with Werlhof's disease at increased risk for bleeding complications when undergoing cardiac surgery?

BACKGROUND: It is generally assumed, that patients with Werlhof's disease (WD) are at increased risk for bleeding complications when undergoing cardiac surgery with extracorporeal circulation. Therefore we performed this case control study to estimate the real risk for bleeding complications of these patients. METHODS: Between 05/95 and 07/98, ten patients with WD (eight males, two females) underwent cardiac surgery employing extracorporeal circulation (WD-group). Five of these patients with platelet counts below 80/nl were treated by immunoglobulins preoperatively. Each patient with WD was matched to five patients without WD (no-WD-group) using diagnosis, age, gender, ejection fraction, number of distal anastomosis and body-mass-index as matching criteria. RESULTS: Mean number of platelet counts were significant lower in the WD-group than in the no-WD-group despite a significant increase of platelet counts after immunoglobulin treatment (54/nl-->112/nl, P=0.018). On the day before, directly after and on the first day after surgery they were 141/nl vs. 215/nl (P=0.012), 75/nl vs. 147/nl (P=0.001) and 93/nl vs. 136/nl (P=0.009). Accordingly, patients of the WD-group received significantly more platelet concentrates than patients of the no-WD-group (mean number of platelet concentrates: 2.3 versus 0.7, P=0.007). Total drainage loss via the mediastinal chest tubes was almost identical (1197 ml in the no-WD-group and 1140 ml in the WD-group). One patient of each group suffered from a bleeding complication requiring reexploration. Three patients of the no-WD-group (6%) and one patient of the WD-group (10%) expired postoperatively unrelated to WD. CONCLUSIONS: Patients with WD may possibly undergo cardiac surgery without a markedly enhanced risk for bleeding complications despite a more than usual transfusion requirement and significantly lower platelet counts perioperatively.

Anticoagulative management of patients requiring left ventricular assist device implantation and suffering from heparin-induced thrombocytopenia type II.

BACKGROUND: Heparin-induced thrombocytopenia type II (HIT II) is a rare but life-threatening side effect of heparin therapy. We describe the perioperative anticoagulative management of patients tested positive for HIT II and requiring implantation of a left ventricular assist device (LVAD). METHODS: We report on 3 patients with a different perioperative anticoagulative management (preoperative, intraoperative, and postoperative anticoagulation with danaparoid-sodium; preoperative anticoagulation with recombinant hirudin, anticoagulation with danaparoid-sodium intraoperatively and postoperatively; preoperative anticoagulation with recombinant hirudin, intraoperative anticoagulation with heparin, and postoperative anticoagulation with danaparoid-sodium) and discuss the difficulties of the treatment. RESULTS: Anticoagulation with alternative drugs such as recombinant hirudin and danaparoid-sodium led to serious and life-threatening bleeding complications as well as to thromboembolic events in the first 2 patients. Therefore the third patient underwent LVAD implantation using heparin for intraoperative anticoagulation to avoid administration of high doses of recombinant hirudin or danaparoid-sodium. Despite very low anti-factor Xa activities, when using danaparoid-sodium postoperatively, the patient suffered from a bleeding complication on the 4th day after LVAD implantation requiring reexploration. CONCLUSIONS: In selected cases (negative heparin-induced platelet aggregation (HIPA) test at the time of LVAD implantation and continuation of postoperative anticoagulation with recombinant hirudin or danaparoid-sodium), heparin may be used for LVAD implantation in HIT II patients to reduce bleeding complications.

Preoperative immunoglobulin treatment in patients with Werlhof's disease undergoing cardiac operation.

BACKGROUND: Patients with Werlhof's disease and undergoing a cardiac surgical procedure with cardiopulmonary bypass are at increased risk for bleeding complications. We report the usefulness of preoperative immunoglobulin treatment in selected patients. METHODS: Between May 1995 and July 1998, 10 patients with Werlhof's disease underwent a cardiac surgical procedure with cardiopulmonary bypass in our department. Five patients with mean platelet counts of less than 80x10(9)/L received immunoglobulin therapy preoperatively (group 1). The other 5 patients with mean platelet counts higher than 80x10(9)/L were not so treated (group 2). RESULTS: In group 1, mean platelet count increased from 54x10(9)/L 5 days before operation to 112x10(9)/L after immunoglobulin treatment (p = 0.018) and did not fall to less than 60x10(9)/L postoperatively. Patients in group 1 received 16 units of packed red blood cells and 5 units of platelet concentrate. Patients in group 2 required 24 units of packed red blood cells, 5 units of platelet concentrate, and 23 units of fresh frozen plasma. Only 1 patient (group 2) had a surgical bleeding complication that required reexploration. Mean drainage loss was 1,100 mL in group 1 and 1,210 mL in group 2. CONCLUSIONS: Our data demonstrate that immunoglobulin treatment of patients with Werlhof's disease and mean platelet counts of less than 80x10(9)/L significantly augments platelet counts preoperatively. It may be useful in selected patients.

The hemodynamic effects of cell-free hemoglobin during general and epidural anesthesia.

UNLABELLED: Although hemoglobin-based oxygen carriers (HBOC) are now being investigated, the effects of HBOC solutions during regional anesthesia have never been analyzed. Therefore, we investigated the hemodynamic changes after HBOC infusion during general anesthesia and thoracic epidural anesthesia. Sheep were assigned to three different groups: a) a control group with six unanesthetized sheep; b) six sheep with a halothane anesthesia (2.0 vol.% in oxygen); and c) six awake sheep with a thoracic epidural anesthesia with bupivacaine. After a period of stabilization, all 18 animals received 100 mg/kg of the HBOC pyridoxalated hemoglobin polyoxyethylene conjugate. The infusion of the HBOC caused a significant increase in mean arterial pressure and pulmonary artery pressure in both the control and epidural anesthesia groups. Anesthesia with halothane reduced the effects of the HBOC-solution on mean arterial pressure but did not abolish the increase in pulmonary artery pressure. Our results demonstrate that vasoconstriction caused by HBOC solutions is not abolished by epidural anesthesia, but halothane anesthesia may alter the hemodynamic effects of HBOC solutions. IMPLICATIONS: We evaluated the effects of epidural anesthesia and halothane anesthesia on the vasoconstrictive properties of a cell-free hemoglobin solution. The vasoconstriction caused by a cell-free hemoglobin solution was similar in unanesthetized sheep and sheep with thoracic epidural anesthesia and was reduced in sheep with halothane anesthesia.

[Pneumothorax in laparoscopic cholecystectomy (II)]. / Pneumothorax während laparoskopischer Cholezystektomie (II).

This case report deals with pneumothorax during elective laparoscopic cholecystectomy in a young woman with no history of severe pulmonary disease. After inflating the capnoperitoneum, pulse oximetry and capnography raised suspicion of pneumothorax whereas the physical examination showed no irregularities. Surgical drapes provided a lack of information from percussion and auscultation. Changing respiratory parameters including the use of pressure-controlled ventilation in absence of tension pneumothorax enabled sufficient ventilation until the insertion of a chest tube. There were no further postoperative complications. Pulse oximetry, capnography and relaxometry proved helpful in monitoring. There may be a benefit from the use of pressure-controlled-ventilation in certain situations, if all changes in volume-controlled-ventilation fail.

p53 Mutations in human hepatocellular carcinomas from Germany.

Mutations in the p53 gene are frequent genetic alterations in human hepatocellular carcinomas. We have examined 13 cases of human hepatocellular carcinomas from Germany for the presence of p53 aberrations in exons 4 to 8 of the gene by single-strand conformation polymorphism and restriction fragment-length polymorphism analyses and by sequencing of polymerase chain reaction products. Single base substitutions occurred in two human hepatocellular carcinomas: a C:G----T:A transition at a CpG site in codon 257, and a T:A----A:T transversion at codon 273. One of these point-mutated tumors and two additional tumors without point mutations demonstrated a loss of one p53 allele. None of the tumors was mutated in codons 12 or 61 of the c-Ha-ras gene.