Gottfried Wechselberger

Activity of Childhood Lupus Nephritis is Linked to Altered T Cell and Cytokine Homeostasis

PurposeStandard therapy for lupus nephritis is based on non-specific immunosuppression. We aimed to identify specific alterations in T cell and cytokine homeostasis and possible associations with disease activity in children with lupus nephritis (LN).MethodsThe phenotype of circulating T cells from children with LN and healthy controls (HC) was analyzed by flow cytometry. Intracellular expression of IL-17 and INF-γ was assessed after stimulation with anti-CD3 and anti-CD28. Serum concentrations of IP10, CCL2, TGF-β, IL-17, and IL-23 were measured by ELISA. Disease activity was determined using the Systemic Lupus Erythematosus Disease Activity Index 2000 update (SLEDAI-2K).ResultsChildren with active LN displayed increased frequencies of effector memory CD4+CD45RO+CCR7− and terminal differentiated CD4+CD45RA+CCR7− T cells and reduced naive CD4+CD45RA+CCR7+ T cells compared to those with inactive LN or HC. Circulating CD4+CXCR3+ and CD4+CCR2+ T cells correlated inversely with the renal SLEDAI-2K, whereas IP10 and CCL2 showed a positive correlation. Reduced CD4+Foxp3+ T cells and serum TFG-β levels in active LN were associated with high serum IL-17 and IL-23 levels and correlated inversely with the renal SLEDAI-2K (r = −0.5855, p = 0.0013 and r = −0.6246, p = 0.0005, respectively), whereas IL-17 and IL-23 correlated positively (r = 0.5516, p = 0.0029 and r = 0.6116, p = 0.0007, respectively). Expansion of Th17 and Th1/Th17 cells in children with LN was significantly greater than in HC (p = 0.0304 and p = 0.0067, respectively).ConclusionChildren with active LN display high levels of pro-inflammatory cytokines associated with an increase in effector T cells and reduction of regulatory T cells. Therapeutic regulation of the aberrant cytokine profile might specifically interrupt pathogenic mechanisms.

Enhanced Activity of Akt in Teff Cells From Children With Lupus Nephritis Is Associated With Reduced Induction of Tumor Necrosis Factor Receptor–Associated Factor 6 and Increased OX40 Expression

OBJECTIVE The breakdown of peripheral tolerance mechanisms is central to the pathogenesis of systemic lupus erythematosus (SLE). Although true Treg cells in patients with SLE exhibit intact suppressive activity, Teff cells are resistant to suppression. The underlying mechanisms are incompletely understood. This study was undertaken to examine the Akt signaling pathway and molecules that may alter its activity in T cells in lupus patients. METHODS The Akt pathway and its regulators were analyzed in Teff and Treg cells from children with lupus nephritis and controls using flow cytometry and real-time quantitative polymerase chain reaction. T cell proliferation was assessed by analysis of 5,6-carboxyfluorescein succinimidyl ester dilution. RESULTS CD4+CD45RA-FoxP3(low) and FoxP3- Teff cells from children with lupus nephritis expressed high levels of activated Akt, resulting in the down-regulation of the proapoptotic protein Bim and an enhanced proliferative response. The induction of tumor necrosis factor receptor-associated factor 6 (TRAF6) was impaired, and TRAF6 levels inversely correlated with Akt activity. Although the expression of OX40 was enhanced on Teff cells from children with lupus nephritis compared to controls, OX40 stimulation failed to significantly increase TRAF6 expression in cells from patients, in contrast to those from healthy controls, but resulted in further increased Akt activation that was reversed by blockade of OX40 signaling. Moreover, inhibition of Akt signaling markedly decreased the proliferation of Teff cells from lupus patients. CONCLUSION Our findings indicate that hyperactivation of the Akt pathway in Teff cells from children with lupus nephritis is associated with reduced induction of TRAF6 and up-regulation of OX40, which may cause Teff cell resistance to Treg cell-mediated suppression.

Temporary closure of full-thickness abdominal-wall defects with mesh grafts

Introduction: A simple technique is presented here for temporarily covering massive, full-thickness, abdominal-wall defects, when they cannot be closed directly. Methods: The exposed viscera can be covered with a meshed split-thickness skin graft to close the wound and seal off the abdominal cavity from the outside. Once the patients general condition improves, the epidermal layer of the mesh graft should be removed by dermabrasion to minimize the risk of epidermal cysts, and the defect should be closed either by primary closure or by a local or free flap, depending on the defect size.

Restoration of elbow flexion after brachial plexus injury by free functional rectus femoris muscle transfer

SUMMARY A 22-year-old patient sustained a complex injury of the left brachial plexus. Primary brachial plexus reconstruction did not lead to any functional recovery. Twenty-six months later, the patient showed an upper brachial plexus palsy, which precluded the possibility for a latissimus dorsi muscle transfer. To re-establish elbow flexion, a free myocutaneous neurovascular rectus femoris flap, harvested from the left thigh, was neurotised to the accessory nerve using a sural nerve graft. Ten months after the free functional rectus femoris transfer, early electromyographic results were detected, and 7 months later, strong reinnervation signs occurred. Due to dissatisfaction with the aesthetic results including an impression in the left shoulder and pectoral region, two silicon implants were inserted 41 months after rectus femoris muscle transfer. A few hours after the operation, the patient experienced palsy of the transplanted muscle. The silicon implants were removed immediately. Initial recovery of muscle function was detected by electromyography 4 months later and complete reinnervation was observed 8 years postoperative. Elbow flexion was rated M4, and the patient had no functional donor-site morbidity. The authors conclude that free rectus femoris muscle transfer offers excellent results when effort is put into postoperative rehabilitation with extensive training programs.

Simplification of Reduction Mammaplasty Using a Specially Designed Ruler

There are well-established techniques for reduction mammaplasty [2 5]. Especially in the beginning of the reduction mammaplasty learning process, inaccurate preoperative marking frequently causes asymmetric results. To prevent this common pitfall, we recommend a simple method for marking exact resection lines with a specially designed ruler for nearly all types of breasts. The ruler, made of transparent plastic, has a triangular shape (Fig. 1). Two straight borders have a centimeter scale including a right angle. The ruler has a red midline and also four black lines marking a 5 distance to the next line. The corner of the scaled borders is the top of the ruler. We perform a modification of the Robbins technique [1]. The initial measurements for the eventual size of the breast and nipple location are performed with them in an upright position. The upper sternal notch and the midclavicular line are marked (Fig. 2). On this line, the new position of the nipple areola is marked at a distance from the upper sternal notch suitable to the size of the patient (as a rule, 19 23 cm). This point should be located at the level of the inframammary crease. Then the top of the pattern is placed on this point, and the midline of the ruler must correspond to the midclavicular line. The lateral borders of the ruler are then marked using an angle of 90 for normal skin or 100 if the skin is flaccid. In the second case, the ruler must be turned to the next black line, which is 5 from the midline. The length of the lateral borders varies 8 to 9 cm depending on the breast size and shape to be achieved. Finally, the submammary fold is marked together with the horizontal incision lines. The lateral incision should not enter the anterior axillary line. The operation is performed with the patient under general anesthesia in a 30 upstanding position. The operation starts with the new size of the areola marked in a circular pattern 4 to 5 cm in diameter suitable to the size of the breast. The site of the inferior pedicle is marked, extending from a 2-cm area around the marked areola superiorly down to a broad base in the inframammary crease. Next, the inferior dermal pedicle to the areola and nipple is denuded. The areola on top of the inferior pedicle is separated from the underlying and adjacent breast tissue by incising around the superior and lateral margins of the areola and the pedicle, separating the areola deeply, but leaving an inner wedge of subcutaneous and breast tissue attached to the pedicle, and also leaving the base of this wedge still attached to the chest wall. The excess of breast tissue is resected along the skin markings, down to the pectoral fascia. A space for the newly formed pedicle is prepared upward of the pectoralis fascia. The breast is reshaped by bringing the medial and lateral skin flaps together, starting with suturing of both lower corners to the appropriate place in the submammary fold. The upper 4 to 4.5 cm of these flaps is temporarily closed (Fig. 3a). The vertical suture line and the inframammary suture line are closed in the usual manner. A suction drain is always used. Finally, the patient is brought to a semi-upright position. The final detailed placement of the nipple areola is always accomplished by comparing one side with the other via fixation of two circular patterns (Fig. 3b). The range of the final location is up to 2 cm. The marked area is denuded, and the temporary suture is removed. Now the nipple is placed in this area. The inferiorly based dermal pedicle technique has been used successfully during the past 10 years. It permits good cosmetic results and appears to satisfy the critical demands of a reduction mammaplasty in terms of safety, reproducibility, and aesthetics (Fig. 3c and d). The Robbins technique for reduction mammaplasty was described in 1977 [4]. The breasts are marked as for the Strömbeck [5] procedure, but the Correspondence to P. Pülzl, M.D.; email: petra.puelzl@ uibk.ac.at Aesth. Plast. Surg. 30:622 624, 2006 DOI: 10.1007/s00266-006-0059-y

Free gracilis muscle flap for treatment of a large temporoparietal defect

Abstract Large defects of the head and neck after excision of a tumour remain a challenge for plastic reconstructive surgeons. A 75-year-old man presented with a Merkel cell carcinoma of the temporoparietal region, and after resection the defect was covered with a gracilis muscle free flap. At 3.7 years follow-up he had an excellent aesthetic result.