Successful tracheal autotransplantation with a vascularized omental flap.

A major problem in tracheal transplantation is the restoration of an adequate vascular supply to the transplanted trachea. In 12 piglets, a segment (6 rings) of thoracic trachea was removed and the excised segment was then sutured back in place. In 9 animals (group A), a vascularized omental flap was wrapped around the autotransplanted trachea. In the other 3 pigs (group B), the omentum was not used. Eight of 9 group A pigs were killed, 1 or 2 months later, having had no signs of airway obstruction; the 9th pig was killed after 14 days because of airway obstruction. The 3 pigs in group B were killed after 11 to 13 days because of progressive respiratory obstruction. In the 8 asymptomatic pigs in group A, the omental flap was viable and tracheal growth was normal with no differences in diameter between normal and autotransplanted trachea. Histologically intact cartilage was lined with respiratory epithelium. In the one group A pig who was killed early, the omental flap was necrotic. In this pig and in the 3 group B animals, extensive tracheal necrosis and nonviable cartilage were observed. These findings indicate that in the pig, a 6-ring segment of trachea can be transplanted with vascularization provided by an omental flap.     

Neuronal regeneration after application of radiofrequency energy to collagenous tissue is affected by limb immobilization: an in vivo animal study.

Despite widespread use of radiofrequency (RF)-shrinkage, there have been no studies on the influence of RF-energy on neural elements of collagenous tissue. The purpose of this study was to examine the effect of RF-shrinkage on neural structures of capsuloligamentous tissue and the recovery of neural elements under different postoperative treatment protocols. One patellar tendon of 46 New-Zealand-White rabbits was shrunk. Six rabbits were sacrificed immediately postoperative. Twenty rabbits were not immobilized, 10 were immobilized for 3 and 10 were immobilized for 6 weeks. A monoclonal antibody, specific against a neurofilament protein, was used to detect nerves and neural structures. Staining pattern of nerve fibres was significantly altered immediately postoperative. After 3 weeks the number of nerve fibres and bundles decreased significantly in immobilized and non-immobilized limbs. The loss of nerve fibres was significantly less in immobilized limbs. At 6 weeks the number of neural elements in immobilized limbs increased to the level of untreated control tissue. In non-immobilized limbs we found no recovery of neural elements 9 weeks postoperatively. At this time the number of nerve fibres and bundles was still significantly less compared to the untreated control limbs. RF-shrinkage causes significant alteration of neural elements. Under immobilization nerve fibres and bundles reach the level of normal untreated tissue. Careful rehabilitation is important after RF-shrinkage. Not only for biomechanical reasons, but also to allow the neural elements to recover, thermally modified tissue should be protected from normal physiologic loads.     

Indikation, OP-Technik und Ergebnisse des endoskopischen Releases der Plantarfaszie (ERPF)

Zusammenfassung Fragestellung Ziel der vorliegenden Untersuchung ist es, die Indikation, OP-Technik sowie die Ergebnisse des endoskopischen Releases der Plantarfaszie darzustellen. Material und Methode An 5 nicht fixierten Präparaten wurde eine biportale Technik zum endoskopischen Release der Plantarfaszie erprobt. Ziel war es hierbei zum einen, die Relation zwischen Plantarfaszie und plantarem Fersensporn zu evaluieren; zum anderen wurde eine Technik erprobt, bei welcher nur 50–70% der medialen Plantarfaszie vom Kalkaneus abgelöst wurde.Über einen Zeitraum von 5 Jahren wurde diese Technik bei 10 männlichen und 7 weiblichen Patienten mit dem klinischen Bild einer Plantarfasziitis durchgeführt. Das mittlere Alter der Patienten betrug 35 Jahre (24–56 Jahre). Alle Patienten durchliefen zunächst konservative Therapieversuche von zumindest 6 Monaten. Ergebnisse Bei den ersten 5 Patienten wurde der Eingriff unter Bildwandlerkontrolle durchgeführt; bei den weiteren Patienten erfolgte die Resektion ohne intraoperative BV-Kontrolle. Bei allen Patienten konnte der Eingriff wie geplant durchgeführt werden. Die endoskopischen Portale heilten ohne Probleme. Die OP-Zeit ist im Rahmen der Lernkurve mit Zeiten zwischen 21 und 74 Minuten (MW: 41 Minuten) noch länger als in der offenen Technik. Der Nachuntersuchungszeitraum betrug zwischen 4 und 48 Monate (MW: 18,5 Monate). Bei 13 der 17 Patienten kam es zu einer klinischen Verbesserung und sie würden den Eingriff erneut durchführen lassen. 7 Patienten zeigten ein gutes und 6 ein sehr gutes Ergebnis im Ogilvie-Harris-Score. Bei 2 Patienten war das initiale Ergebnis nicht zufriedenstellend. Die Ursache hier lag in einer ossären Übermüdungsreaktion des Kalkaneus. Diese Komplikation wurde durch Entlastung über 6 Wochen symptomastisch behandelt. Bei zwei weiteren Patienten stellten sich sekundäre Überlastungen am lateralen Fußrand ein. Im Rahmen der frühen Rehabilitationsphase war es wichtig, trotz des minimalinvasiven Vorgehens, eine vorsichtige Belastungssteigerung durchzuführen. Schlussfolgerung Die Technik des endoskopischen Releases der Plantarfaszie (ERPF) ist standardisiert und reproduzierbar durchführbar. Sie führt zu guten mittelfristigen Ergebnissen. Ein Stabilitätsverlust der plantaren Verspannung sollte jedoch unbedingt vermieden werden.     

Reduced tracheal growth after reconstruction with pericardium

Four groups of piglets were used to test the use of pericardium and periosteum as free grafts in the repair of full thickness cervical tracheal defects. Pericardium provided an airtight, rapidly healing graft, but did not give sufficient structural rigidity to prevent narrowing and growth failure at the graft site. Composite grafts of pericardium and periosteum were also unsatisfactory, in that the periosteum failed to produce enough bone to prevent collapse of the graft. Since previous studies have shown that periosteal grafts result in good bone formation when applied alone or as an extramucosal support, it is concluded that the osteogenic potential is dependent on the available blood supply and speed of revascularization. It appears that the presence of pericardium in the composite grafts may have inhibited this property.     

APSA: a forum for progress in pediatric surgery.

The APSA scientific program has indeed been a forum for progress for a broad spectrum of medical and surgical problems affecting infants and children. Significant contributions from studies at the bedside and in the laboratory have been made by an extraordinarily large percent of APSA members from both children's and general hospitals. In addition to the many advances that apply to our own specialty, fundamental advances have been recognized and accepted by others. Developments for the future have been identified and our entire membership can be proud of the wonderful achievements of the last 20 years of APSA scientific programs. Finally, I thank you all for giving me the honor to serve as the President of this outstanding organization, which has accomplished so much already, but whose best days are yet to come.     

Repair of long tracheal defects with cryopreserved cartilaginous allografts.

Tracheoplasties with various autografts (cartilage, periosteum, pericardium) have been used in the treatment of long-segment tracheal stenosis. Previous studies have shown that cartilage allografts survive transplantation on a long-term basis in various sites of the body. In this study we set out to determine if cryopreserved cartilage and cryopreserved tracheal allografts would survive when used to cover tracheal defects in animals. A rectangular defect (2.8 +/- 0.3 cm long and incorporating 50% of tracheal circumference) was created in the thoracic trachea of 18 piglets. The defect was covered with the excised tracheal segment in 6 (group A, control group), with a cryopreserved tracheal allograft in 6 (group B), and with a cryopreserved cartilage allograft harvested from the scapula in 6 (group C). The allografts were cryopreserved, by a standard slow-freezing technique, at -80 degrees C for more than 21 days. All animals survived the grafting procedure and were killed after 2 months. None had signs of airway obstruction. Using the trachea above the defect as the standard, the mean sagittal narrowing of the airway in the repaired trachea was 0.4 mm in group A, 0.7 mm in group B, and 0.6 mm in group C; the coronal diameter in normal and grafted trachea was similar. The lumen of all grafts was lined by regenerating respiratory epithelium, and cilia were seen in many. Some cartilage was reabsorbed in group A and B but cartilage islands were present in all. In group A, reabsorption of cartilage was minimal. These findings suggest that segments of trachea or cartilage allografts can be cryopreserved, stored, and, subsequently, used when necessary for tracheoplasty.     

Pharmacokinetics of tacrolimus (FK 506) in children and adolescents with renal transplants

Background: Only few data exist on pharmacokinetics of tacrolimus in children. Patients: In 1995 and 1996, 14 children (mean age 13 years, range 5-23 years) received tacrolimus after renal transplantation; 10 of these after biopsy-proven steroid-resistant rejection (2 with vascular rejection), two for cyclosporin A (CsA)-induced severe nephrotoxicity, one for untreatable gingival hyperplasia on CsA, and one child was treated primarily after transplantation because of severe liver involvement in nephronophthisis. Pharmacokinetic investigations were performed after establishing a stable maintenance dose with trough levels in the desired window of 5-12 ng/ml. Results: Mean follow-up time was 6 months (range 3-25 months). Eleven patients were still on tacrolimus. Two were discontinued because of severe aggravation of chronic persistent hepatitis C (one of them also developed diabetes mellitus),and one patient was subsequently switched to conventional immunosuppression because of tacrolimus-associated nephrotoxicity. All tacrolimus levels were measured by a modified assay (MEIA, Tacrolimus, Abbott) with improved sensitivity. At the time of switch, median serum creatinine was 234±82 7mgr;mol;l and 6 months after switch 201±99 &mgr;mol/l. All grafts are still functioning. Mean FK-506 dose was 0.16 mg/kg body weight/day (range 0.036-0.30 mg/kg). Mean trough level was 7.1±2.6 ng/ml in the morning and 6.5±2.0 ng/ml in the evening. Median time of maximum concentration (tmax) was 120 min after application, and the mean maximum concentration (Cmax) was 15.2±6.7 ng/ml. Mean area under the curve (AUC) was 104±33 ng * h/ml, with a range from 65 to 169 ng * h/ml. No patient had unsatisfactorily low trough levels during the study. There was only a weak but significant (P<0.05) correlation between dose per kg body weight and AUC and, as expected, an excellent correlation (r²=0.73, P<0.001) between AUC and trough level. Conclusion: Because of interindividual variation between patients, therapeutic drug monitoring of tacrolimus is mandatory. In this study, a daily dose of 0.15 mg/kg was sufficient in most patients. We recommend the performance of at least one pharmacokinetic study after establishing stable FK 506 trough levels to ascertain a safe profile.     

Mechanisms by which Candida albicans induces endothelial cell prostaglandin synthesis.

One strategy for improving resistance to opportunistic pathogens is to determine host cellular responses during the invasion process and upregulate those responses that are relevant to host defense mechanisms. Within this context, we have shown previously that invasion of endothelial cells by Candida albicans in vitro causes increased production of prostaglandins. As a prerequisite for modulating endothelial cell prostaglandin production, we now characterize the mechanisms through which this process occurs. Endothelial cell invasion by C. albicans appeared to stimulate the conversion of arachidonic acid into prostaglandins by upregulating the synthesis of endothelial cell cyclooxygenase and increasing the activity of the endothelial cell phospholipase. The enhanced activities of these two enzymes were independent of calphostin C-sensitive protein kinase C and resulted in the increased production and extracellular secretion of prostaglandin I2 (PGI2), PGF2 alpha, and PGE2. The secretion of these prostaglandins had no effect on the amount of endothelial cell injury induced by C. albicans. The role of the increased prostaglandin secretion by endothelial cells is likely related to modulation of the leukocyte response at the candida-leukocyte-endothelial cell interface.     

Adherence to and damage of endothelial cells by Cryptococcus neoformans in vitro: role of the capsule.

Escape from the intravascular compartment is likely a critical step in the development of hematogenously disseminated cryptococcal infections, such as meningitis. The capsule of Cryptococcus neoformans is considered to be a virulence factor because of its antiphagocytic properties. To further investigate the role of the capsule in escape from the intravascular compartment, we used isogenic strain pairs, an acapsular mutant, and an encapsulated clinical isolate to determine the effects of the capsule of C. neoformans on adherence to, phagocytosis by, and damage of endothelial cells in vitro. Acapsular C. neoformans adhered significantly more to endothelial cells and caused greater endothelial cell injury than did encapsulated organisms. Coating of an acapsular strain with cryptococcal glucuronoxylomannan decreased both adherence to and damage of endothelial cells by 61.7% +/- 9.1% and 76.6% +/- 10.2%, respectively. Transmission electron microscopy demonstrated internalization of acapsular, but not encapsulated, organisms by endothelial cells. Internalization of an acapsular strain occurred through endothelial cell phagocytosis and was inhibited by cytochalasin D. Phagocytosis required a heat-labile serum factor, probably complement. These results suggest that acapsular or poorly encapsulated C. neoformans may be the form(s) that escapes from the vasculature during initiation of hematogenously disseminated disease.     

Resistance to platelet microbicidal protein results in increased severity of experimental Candida albicans endocarditis.

Thrombin-induced platelet microbicidal protein (tPMP) exerts potent in vitro microbicidal activity against pathogens commonly found in the bloodstream, including Staphylococcus aureus, Staphylococcus epidermidis, and Candida albicans. Localized platelet release of tPMP may be important in defense against infections involving the vascular endothelium caused by tPMP-susceptible organisms. In contrast, pathogens capable of surviving in the presence of tPMP could then exploit the platelet as an adhesive surface for attachment to damaged endothelium. To examine these hypotheses, we derived a tPMP-resistant (tPMP(r)) C. albicans strain from its tPMP-sensitive (tPMP(s)) parental strains were equivalent in vitro as assessed by genotyping (electrophoretic karyotype and restriction endonuclease analysis of genomic DNA), biotyping, germination, platelet aggregation, adherence to vascular endothelial cells, and growth characteristics. In addition, the tPMP(r) phenotype was stable following multiple in vitro and in vivo passages. We then investigated the in vivo relevance of tPMP susceptibility on endovascular infection using a rabbit model of endocarditis and hematogenous dissemination. Rabbits with transaortic catheters (n = 15 in each group) were challenged with either the tPMP(s) or tPMP(r) C. albicans strain. All rabbits developed C. albicans-induced endocarditis, as determined by the presence of infected vegetations. In rabbits challenged with tPMP(s) strain (P < 0.001). These results were seen in the absence of differences in either initial adherence of strains to cardiac valves or vegetation weights. Furthermore, although these C. albicans strains induced equivalent rates and extent of hematogenous renal infection, only the tPMP(r) strain disseminated hematogenously to the spleen (15 of 15 rabbits) versus 0 of 15 [tpmp(s) strain]; P < 0.0001). Thus, tPMP(r) C. albicans caused more-severe endocarditis and produced greater metastatic sequelae than the tPMP(s) counterpart.