Current indications for hand and face allotransplantation.

There is growing excitement centered on the possibilities of composite tissue allotransplantation (CTA) in many medical centers around the United States. As CTA programs begin to form, criteria to guide patient selection for these highly complex procedures is warranted. At this time the contraindications for CTA are more easily defined than the indications. What is clear is that a thorough multidisciplinary evaluation of each individual patient will be needed to determine the global impact and complexity of the defect. The role of the surgeon is to identify the feasibility of the CTA reconstruction and balance this with a complete knowledge of conventional reconstructive techniques. Conventional treatments may be used in place of CTA or as salvage for CTA failure.

Increased signs of acute rejection with ischemic time in a rat musculocutaneous allotransplant model.

BACKGROUND: Composite tissue allotransplantation (CTA) may restore a variety of tissue defects, but carries the potential risks of graft failure and/or immunosuppression-related complications. Ischemia-reperfusion injury has been documented in CTA is known to contribute to acute rejection of solid organ grafts. This study describes the influence of subcritical ischemic time (ie, ischemia sufficient to generate reversible cell damage) on signs of rejection of musculocutaneous allograft components of subcritical ischemic time, namely, ischemia sufficient to generate reversible cell injury. Although skin is considered the most antigenic component of a composite allograft and is currently used for rejection surveillance, muscle and adipose are more susceptible to ischemia-related injury. METHODS: Vascularized epigastric flaps were transplanted from WKY to Fisher 344 rats after 1 or 3 hours of ischemia. Biopsies taken on postoperative day 6 were graded for signs of acute rejection according to criteria modified from previously published grading systems for CTA rejection. RESULTS: Skin and muscle exposed to 3 hours of ischemia showed significantly higher rejection scores than after 1 hour of ischemia, as evidenced by a more aggressive diffuse lymphocytic infiltration with disruption of tissue architecture. The rejection score in skin with 3-hour ischemia was 5.0 +/- 0.1 versus 3.7 +/- 0.2 with 1-hour (Mann-Whitney U test; P < .05). The rejection score in muscle exposed to 3-hour ischemia was 3.6 +/- 0.3 versus 2.5 +/- 0.1 with 1-hour (P < .05). CONCLUSIONS: Muscle and skin demonstrated increased acute rejection of allotransplants with increased subcritical ischemic time. This study supports the use of aggressive methods to reduce subcritical ischemic injury during allotransplantation of composite tissue and inclusion of muscle in postoperative biopsies in this early investigational period of CTA.

[Facial allograft transplantation: fiction or reality? Surgical techniques in a fresh human cadaver model]. / Allogene Gesichtstransplantation: Fiktion oder Realität? : Darstellung chirurgischer Techniken am Leichenmodel.

BACKGROUND: The aim of this study was to describe two methods of face-harvesting techniques -- a skin and soft tissue flap and a combined osteocutaneous flap -- and to demonstrate the compatibility between donor and recipient in a human fresh cadaver model. METHODS: In fresh human cadavers the skin and soft tissue of the face (type 1) and a combined osteocutaneous flap (including a le Fort III segment, type 2) were harvested. The faces were subsequently exchanged among the donor crania, simulating full-face transplantation. RESULTS: Both flaps are based on the external blood supply of the faciotemporal vessels and the external jugular vein. The end branches of the trigeminal nerve could potentially be used for restoration of sensation (type 1 flap). With type 2 flaps the facial expression may be restored with the inclusion of the facial nerve. Four morphological parameters determine the donor/recipient compatibility: skin color and texture, anthropometric head dimensions, specific soft tissue components (nose, lip, cheek, and eyebrow), and gender. CONCLUSION: Apart from ethical considerations, long-term immunosuppression will remain the limiting factor of full facial transplantation in the near future.

A clinically applicable reporting system for the diagnosis of facial fractures.

A clinically applicable, comprehensive reporting system for the diagnosis of facial fractures was developed with three guiding principles: (1) preservation of classical anatomical terminology and nomenclature, (2) facilitation of uniform interpretation of radiographs between radiologists and (3) non-redundant diagnostic descriptions of complex fractures, in a manner that correlates with treatment modality. Twenty-two fracture types (17 simple fracture types and 5 complex fracture types) are included in the system. Each patient's fracture pattern is described by listing the component fractures present. A short narrative (modifying description) is provided after each fracture listed. Simple fractures that help to comprise more complex fractures are not listed separately, but are described within the modifying description of the complex fracture they help to comprise. When components of multiple complex fractures are present, a hierarchy of complex fractures dictates which fracture is described first. Additional complex fractures are only described separately when they do not share common components. In all other cases, the second (lower order) complex fracture is best described by simply listing the component (simple or complex) fractures that are not accounted for in the higher order complex fracture. Adoption of this reporting system should improve communication between emergency medicine physicians, radiologists and surgeons.

[Current concepts and trends in post-bariatric plastic surgery]. / Plastische Chirurgie nach forcierter Gewichtsreduktion--"Kosmetik" oder Rekonstruktion?

The epidemic-like increase of obesity in all western countries is associated with a growing incidence of morbid obesity. Here, efficient and lasting weight loss is mostly obtained by surgical interventions today performed in a reliable and safe manner. In that way comorbidities associated with obesity can be reduced or abolished. Treating the sequelae of bariatric surgery, with frequent massive weight loss and generalized skin excess, is challenging for the plastic surgeon. The goal is to restore a normal body contour as a prerequisite for complete psychosocial integration of the patients, who are often stigmatized by their outward appearance not only before but also after the weight loss. The present work provides an overview of current concepts and trends in post-bariatric plastic surgery.

[Near-total ear amputation: anatomical bases and management]. / Subtotale Amputation des Ohrs: Anatomische Grundlagen und Management.

BACKGROUND: In cases of near-total ear avulsions, replantation is often successful without microsurgery. The purpose of our study was to investigate the relevant vascular anatomy associated for ear survival. PATIENTS AND METHODS: Four cases of successful surgical intervention in near-total ear avulsions are presented. Injection studies using latex were performed to identify the blood supply to the auricle on 13 cadaveric ears. RESULTS: A small superior branch of the superficial temporal artery above the tragus was identified extending along the upper border of the auricle and connecting with the helical arcade. Below the tragus, a second small horizontal branch of the superficial temporal artery was identified. CONCLUSION: The auricle can survive near-total amputation based on a skin bridge above or below the tragus. One of the auricular branches of the superficial temporal artery seems sufficient for the blood supply to the ear and allows for a successful non-microsurgical operative repair.

Effects of glutamine, glucose, and oxygen concentration on the metabolism and proliferation of rabbit adipose-derived stem cells.

The use of adipose-derived stem cells (ASCs) for tissue engineering involves exposing them to metabolically adverse conditions. This study examined the metabolism, proliferation, and viability of ASCs under various oxygen, glucose, and glutamine concentrations to determine how these cells respond to such environments. ASCs were cultured in each of 8 media preparations containing 4.8 or 21.5 mM glucose, and 0, 2, 4, or 6 mM glutamine. The ASCs were cultured under normoxic (20% O(2)) and hypoxic (0.1% O(2)) conditions. Conditioned media were collected and assayed for glucose, glutamine, lactate, pyruvate, and glutamate. Cell proliferation and cell death were measured after 5 days of culture. ASCs remained metabolically active under all culture conditions; however, their proliferation rate was significantly reduced in the absence of glutamine. Hypoxia resulted in increased cell death. ASCs are a viable source of stem cells for tissue engineering purposes, although substantial challenges remain. These cells are able to survive in environments with limited oxygen and glutamine and thus may be able to survive brief periods of limited nutrient transport after implantation.

[Literature and own strategies concerning soft-tissue reconstruction and exposed osteosynthetic hardware]. / Weichteildefekt und exponiertes Osteosynthesematerial--Metallerhalt oder Entfernung? Literaturübersicht und eigene Strategien.

BACKGROUND: In the event of exposed hardware from reconstructive surgery, it must be decided whether to retain or remove it prior to plastic surgical soft-tissue reconstruction to ensure long-term freedom from infection and stable wound closure. MATERIAL AND METHODS: Treatment options and results in the literature are reviewed. A treatment algorithm is proposed under consideration of our personal experience. RESULTS AND CONCLUSION: Hardware used in spine surgery is commonly left in situ until bony consolidation has been achieved. The indications for hardware removal depend on length of exposure or infection, implant failure, and location. Osteosynthetic devices in the extremities may be removed and replaced by external fixators or immobilisation. Removal of prostheses requires complex second-stage reimplantation or arthrodesis. A treatment algorithm is suggested that might ease the decision whether exposed hardware can remain or requires removal before reconstruction of soft-tissue defects.

[Current treatment of hamate hook fractures]. / Aktuelle Behandlung der Hamulus ossis hamati-Fraktur.

PURPOSE: Hamate hook fractures can be treated conservatively or surgically, whereby fragment and fracture position, age of the fracture, associated injuries, and individual needs of the patient all influence the choice of the therapeutic procedure. Acute non-displaced fractures are frequently treated conservatively, while displaced fractures and nonunions undergo surgical treatment. We report our experience in diagnostic and therapeutic management of 14 hamate hook fractures. CLINICAL MATERIAL AND METHOD: During a three-year period, 14 patients (eleven men and three women) 21 to 73 years old (42.0 +/- 17.9 years) with fractures at the base of the hamate hook were treated at three hand surgery units. The retrospective study of all patients included a chart review, postoperative radiological imaging after one year, and clinical examinations with grip strength measurements after 18 to 34 months (27.8 +/- 4.9 months). In six patients (43 %), the acute fracture was immobilized in a lower arm cast for six weeks, while eight patients (57 %) were operated primarily. In five cases (36 %) excision of the fragment and in three cases (21 %) open reduction and internal fixation using a screw were performed. Of six patients treated conservatively, five developed nonunion after two to five months (3.0 +/- 1.2 months) with persistent pain and underwent secondary surgery. One patient was asymptomatic despite a nonunion and declined surgical treatment. In three cases the fragment was excised, while two patients underwent open reduction and internal fixation with a screw. RESULTS: All patients operated primarily were free of complaints three months after surgery. The success rate of surgical treatment (8/8) was therefore significantly higher than that after conservative treatment (1/6). CONCLUSION: Compared to conservative treatment of acute non-displaced hamate hook fractures, which is associated with a high risk of developing symptomatic nonunion, primary surgical treatment reliably yields a good clinical outcome. Here, results after fragment excision and open reduction and internal fixation are comparable.

[The infragluteal perforator flap]. / Die infragluteale Perforans-Lappenplastik.

PURPOSE: Pressure sores of the ischial tuberosities are mostly covered with fascio- or myocutaneous flaps of the posterior thigh. In doing so, vascular territories of adjacent flaps are violated, which are not available any more in case of ulcer recurrences. In consideration of the high recurrence rates of pressure sores in paraplegics, we developed an infragluteal perforator flap that spares adjacent vascular territories. PATIENTS/MATERIAL AND METHOD: Infragluteal perforator flaps were dissected in five fresh human cadavers to investigate the anatomic relations of the cutaneous branches of the inferior gluteal artery and the inferior clunial nerves and to define the anatomic landmarks for clinical application of an innervated flap. In six paraplegic patients with primary (5/6) and secondary (1/6) pressure sores of the ischial tuberosity, infragluteal perforator flaps were used for wound coverage. The donor defect was closed primarily and postoperative care and patient mobilisation followed a standardised protocol. RESULTS: In eleven infragluteal perforator flaps that were dissected in cadavers and patients, we found one or two cutaneous branches of the descending branch of the inferior gluteal artery at the lower border of the gluteus maximus muscle that supplied the infragluteal skin. Infragluteal perforator flaps could be harvested on these perforator vessels and transferred to the ischial defects without tension due to the excellent mobility of the skin island. The descending branch of the inferior gluteal artery could be spared in all cases for future flaps. In one patient with multiple recurrences of an ischial pressure sore flap necrosis occurred due to venous congestion. The other five infragluteal perforator flaps healed without complications. CONCLUSION: The infragluteal perforator flap is suitable for the closure of pressure sores of the ischial tuberosities and can be used as a sensitised flap by inclusion of the inferior clunial nerves. Compared to traditional pedicled flaps of the posterior thigh, the infragluteal perforator flap reduces donor site morbidity and spares the vascular territories of adjacent flaps for future recurrent ulcers.

Proteasome inhibitor induced gene expression profiles reveal overexpression of transcriptional regulators ATF3, GADD153 and MAD1.

The ubiquitin/proteasome pathway has been implicated in a wide variety of cellular processes and the number of substrates degraded by the proteasome is impressive. Most prominently, the stability of a large number of transcription factors is regulated by ubiquitination. To elucidate pathways regulated by the proteasome, gene expression profiles were generated, comparing changes of mRNA expression of 7900 genes from the UniGene collection upon exposure of cells to the proteasome inhibitors Lactacystin, Lactacystin-beta-lactone or MG132 by means of microarray based cDNA hybridization. The three profiles were very similar, but differed significantly from a gene expression profile generated with the histone deacetylase inhibitor Trapoxin A, indicating that the observed alterations were indeed due to proteasome inhibition. Two of the most prominently induced genes encoded the growth arrest and DNA damage inducible protein Gadd153 and the activating transcription factor ATF3, both transcription factors of the CCAAT/enhancer binding protein (C/EBP) family. A third gene encoded for the transcriptional repressor and c-Myc antagonist Mad1. Our results suggest that proteasome inhibition leads to upregulation of specific members of transcription factor families controlling cellular stress response and proliferation. Oncogene (2000).

Stepwise cloning and genetic organization of the seemingly unclonable HgiCII restriction-modification system from Herpetosiphon giganteus strain Hpg9, using PCR technique.

The genes, hgiCIIR and hgiCIIM, that encode the HgiCII restriction and modification (R-M) system from Herpetosiphon giganteus strain Hpg9, an AvaII isoschizomer recognizing the sequence, GGATCC, were cloned in Escherichia coli. Cloning the respective hgiCIIM gene was achieved via in vitro selection both from a Sau3AI- and an NheI-generated plasmid gene library using AvaII, a commercially available isoschizomer of HgiCII. However, all attempts to clone the closely linked hgiCIIR and M genes in a single step resulted in deletions spanning parts of the coding region of hgiCIIR. Therefore, cloning of the missing 3'-terminal part of this gene was achieved by applying the inverse polymerase-chain-reaction technique. All attempts to construct an enzymatically active R.HgiCII failed; only the inactivated hgiCIIR gene could be cloned. Sequencing of the hgiCIIRM region (carrying predesigned small mutations in the R gene) disclosed three open reading frames (ORFs): one small ORF preceding the methltransferase (MTase)-encoding gene, plus those encoding M.HgiCII (49,620 Da) and R.HgiCII (30,891 Da). M.HgiCII exhibits the common motif of ten conserved amino-acid blocks typically found within the group of m5C-MTases. The R-M system of HgiCII reveals strong homologies to the isoschizomeric R-M system of HgiBI from H. giganteus strain Hpg5, which, in contrast, could be cloned in one step.

Organization and gene expression within restriction-modification systems of Herpetosiphon giganteus.

We have characterized a family of related restriction-modification (R-M) systems from the soil bacterium Herpetosiphon giganteus (Hgi). A comparison of their genetic organization reveals two types of regulatory proteins, called controlling ORF C. While one of these small reading frames derived from RM.HgiCI seems to be an enhancer of its own promoter, evidence is provided for a silencer function of the other ORF C derived from the closely related AvaII-type systems RM.HgiBI/CII/EI. The respective silencer function is detected during our various attempts to clone three isoschizomers with unusually high differences in their specific activity. Sequencing and site-directed mutagenesis revealed just two amino acids as being responsible for a massive increase in specific activity of these endonucleases.

Metabolism of 3-methyldiphenyl ether by Sphingomonas sp. SS31.

The bacterium Sphingomonas sp. SS31, which was obtained from the diphenyl ether-degrading strain Sphingomonas sp. SS3 by an adaptation process, utilized 3-methyldiphenyl ether for growth in addition to diphenyl ether. The initial enzymatic attack onto this compound proceeded by a regioselective, but non-specific dioxygenation at the carbon carrying the ether bridge and the adjacent carbon of the unsubstituted as well as the methyl-substituted aromatic nucleus. Upon spontaneous decomposition, the resulting unstable hemiacetal structure yielded 3-methylphenol and catechol, or phenol, 3-methylcatechol, and 4-methylcatechol, respectively. Phenol and 3-methylphenol were oxidized to the corresponding catechols which, after subsequent ortho-cleavage, were channeled into the oxoadipate pathway.

Treatment of segmental defects of the humerus with an osteoseptocutaneous fibular transplant.

BACKGROUND: There are limited reconstructive options for the treatment of segmental bone defects of the upper extremity that are >6 cm in length, especially those that are associated with soft-tissue defects. The purpose of the present review was to report on our experience with fifteen patients who received an osteoseptocutaneous fibular transplant for reconstruction of a humeral defect. METHODS: The study cohort included eight male patients and seven female patients with an average age of forty-one years. The indications for the procedure included segmental nonunion (nine patients), a gunshot wound (three), a defect at the site of a tumor resection (two), and failure of an allograft-prosthesis reconstruction (one). The fibular graft was fixed by means of intramedullary impaction in eleven patients, was used as an onlay graft in three, and was used as a strut between the intact diaphysis and the humeral head in one. RESULTS: The average length of the segmental humeral defect was 9.3 cm. The average length of the fibular graft was 16.1 cm, and the average length and width of the skin paddle were 8.1 and 4.5 cm. The average duration of follow-up was twenty-four months. Three patients had venous thrombosis and underwent a successful revision of the anastomosis. Four patients had early failure of graft fixation. Three patients had a fracture of the fibular graft within the first year postoperatively. All but one of these latter seven patients were successfully treated with open reduction, internal fixation, and additional bone-grafting. One patient with an infection at the site of a nonunion and signs of graft resorption required a second fibular transplant. CONCLUSIONS: The osteoseptocutaneous fibular transplant is an effective treatment for combined segmental osseous and soft-tissue defects of the arm. However, the application of this technique to the arm is more complex than application to the forearm and is associated with a higher rate of complications.

Treatment of a severe alkali burn.

The case history of a 20-year-old male patient who sustained an 85 per cent total body surface area alkali burn to his skin, after falling into a caustic lime pit, is reported. Considerable problems regarding the correct estimate of burn wound depth, predominant location of the deepest burn on the posterior half of the body, appropriate wound coverage, and lack of sufficient skin graft donor sites required a complex treatment plan. Excisions to fascia and intradermal debridement were required to achieve an appropriate bed for wound closure. Five per cent mafenide acetate solution (Sulfamylon) was applied to prevent burn wound sepsis. Human allografts and Biobrane were used extensively to achieve temporary wound closure, to provide mechanical protection of freshly autografted wounds, and to prevent desiccation following application of cultured epidermal autografts on to debrided wounds and split thickness skin grafted donor sites. The case illustrates a number of problems associated with the evaluation and treatment of patients suffering severe alkali burns, and demonstrates the implementation of both established and evolving technologies in the management of these injuries.

The concept of fillet flaps: classification, indications, and analysis of their clinical value.

Tissue of amputated or nonsalvageable limbs may be used for reconstruction of complex defects resulting from tumor and trauma. This is the "spare parts" concept. By definition, fillet flaps are axial-pattern flaps that can function as composite-tissue transfers. They can be used as pedicled or free flaps and are a beneficial reconstruction strategy for major defects, provided there is tissue available adjacent to these defects.From 1988 to 1999, 104 fillet flap procedures were performed on 94 patients (50 pedicled finger and toe fillets, 36 pedicled limb fillets, and 18 free microsurgical fillet flaps). Nineteen pedicled finger fillets were used for defects of the dorsum or volar aspect of the hand, and 14 digital defects and 11 defects of the forefoot were covered with pedicled fillets from adjacent toes and fingers. The average size of the defects was 23 cm2. Fourteen fingers were salvaged. Eleven ray amputations, two extended procedures for coverage of the hand, and nine forefoot amputations were prevented. In four cases, a partial or total necrosis of a fillet flap occurred (one patient with diabetic vascular disease, one with Dupuytren's contracture, and two with high-voltage electrical injuries).Thirty-six pedicled limb fillet flaps were used in 35 cases. In 12 cases, salvage of above-knee or below-knee amputated stumps was achieved with a plantar neurovascular island pedicled flap. In seven other cases, sacral, pelvic, groin, hip, abdominal wall, or lumbar defects were reconstructed with fillet-of-thigh or entire-limb fillet flaps. In five cases, defects of shoulder, head, neck, and thoracic wall were covered with upper-arm fillet flaps. In nine cases, defects of the forefoot were covered by adjacent dorsal or plantar fillet flaps. In two other cases, defects of the upper arm or the proximal forearm were reconstructed with a forearm fillet. The average size of these defects was 512 cm2. Thirteen major joints were salvaged, three stumps were lengthened, and nine foot or forefoot amputations were prevented. One partial flap necrosis occurred in a patient with a fillet-of-sole flap. In another case, wound infection required revision and above-knee amputation with removal of the flap.Nine free plantar fillet flaps were performed-five for coverage of amputation stumps and four for sacral pressure sores. Seven free forearm fillet flaps, one free flap of forearm and hand, and one forearm and distal upper-arm fillet flap were performed for defect coverage of the shoulder and neck area. The average size of these defects was 432 cm2. Four knee joints were salvaged and one above-knee stump was lengthened. No flap necrosis was observed. One patient died of acute respiratory distress syndrome 6 days after surgery. Major complications were predominantly encountered in small finger and toe fillet flaps. Overall complication rate, including wound dehiscence and secondary grafting, was 18 percent. This complication rate seems acceptable. Major complications such as flap loss, flap revision, or severe infection occurred in only 7.5 percent of cases. The majority of our cases resulted from severe trauma with infected and necrotic soft tissues, disseminated tumor disease, or ulcers in elderly, multimorbid patients. On the basis of these data, a classification was developed that facilitates multicenter comparison of procedures and their clinical success. Fillet flaps facilitate reconstruction in difficult and complex cases. The spare part concept should be integrated into each trauma algorithm to avoid additional donor-site morbidity and facilitate stump-length preservation or limb salvage.

The IRMM--International Measurement Evaluation Program (IMEP). IMEP-3--trace elements in synthetic and natural water.

The aim of the IRMM--International Measurement Evaluation Program (IMEP) is to test out a possible realization of international measurement comparability for field laboratories through traceability of their measurements to the SI Unit for amount of substance: the mole. In IMEP-3, 10 different trace elements, B, Ca, Cd, Cu, Fe, K, Li, Pb, Rb, and Zn, were determined in a synthetic and a natural water by participating laboratories using their routine methods and graphically compared (in coded form) to certified values, established by IRMM and NIST using an isotope-specific method (Isotope Dilution Mass Spectrometry, Neutron Activation Analysis). The number of participants was 70; 64 laboratories have reported results. The results show a spread of more than 50% asymmetrically around the certified value. The Youden graphs allow evaluation of the overall performance of the laboratories in the IMEP-3 round.

Congenital neuroepithelioma in an infant hand.

We describe a congenital peripheral neuroepithelioma of the hand in an infant aged 6 weeks. This primitive malignant tumour of neuroepithelial origin is extremely rare in neonates. Peripheral neuroepitheliomas of the hand have not been described in the literature previously. Specific diagnosis and the current therapeutic approaches are discussed.

Skin allograft rejection and hyperbaric oxygen treatment in immune-histoincompatible mice.

The effect of hyperbaric oxygen (HBO) as an immunosuppressive agent was evaluated by using a highly immunogenic skin allograft mouse model. Immune-histoincompatible female C57BL/6 and BALB/c mice (N = 30) were randomly assigned to three groups receiving no treatment (control group), low dose HBO treatment (two treatments once a week), and intermediate HBO treatment (two treatments 3 times/wk) 1 wk before and 2 wk after transplantation of a 1.5 x 2 cm full thickness skin allograft from the back. Rejection was observed a Day 7 and was completed 14 days after surgery in controls. Low dose and intermediate HBO treatment delayed skin allograft rejection, which was histologically confirmed.