Cytokine manipulation of explanted Dupuytren's affected human palmar fascia.

INTRODUCTION: Dupuytren's disease plagues human hands and digits producing fibrotic nodules and fascial cords with resultant debilitating flexion contracture deformities. Interest in this condition is great but because the disease is specific to humans and study has been hampered by the lack of an in vivo model. By utilizing an in vivo "nude" rat model it is possible to maintain and study explanted Dupuytren's contracted palmar fascia for prolonged periods of time. MATERIALS AND METHODS: Human specimens were divided into four, one for in vitro analysis, and three for model explantation. The explanted tissue was perfused with either transforming growth factor beta-2 (TGFbeta2), its antibody, or a control vehicle. Explant biopsies were obtained at 30 and 60 days and compared to tissue prior to explantation. Immunohistochemistry of collagen I and III, DNA synthesis, protein production, and fibroblast kinetics were serially determined. RESULTS: Perfusion of explanted Dupuytren's tissue by TGFbeta2 upregulated collagen I and III from biopsies obtained from the explants at 30 days when compared to vehicle control (P < 0.001). Perfusion with antibody prevented this upregulation when compared to vehicle control (P < 0.001). Cell cultures derived from fibroblasts obtained from biopsies of the explants perfused with TGFbeta2 increased DNA synthesis, protein production and fibroblast kinetics. CONCLUSION: These findings paralleled those from other fibroproliferative disorders suggesting a role for TGFbeta2 in the pathogenesis of Dupuytren's contracture as well as possible novel treatment approaches.

Results of 268 pressure sores in 158 patients managed jointly by plastic surgery and rehabilitation medicine.

Despite improvements in surgical repair of pressure sores, recurrence rates greater than 80 percent are reported, thus indicating that this difficult problem is not yet solved. Recurrence results in additional hospitalizations and increased medical expenses. Because associated general clinical and social issues are numerous for these patients, our physical medicine and rehabilitation colleagues are active participants in their perioperative medical care. In addition, the Department of Physical Medicine and Rehabilitation also directs a complete postreconstruction rehabilitation and education program for them. The results of surgically repaired pressure sores for patients managed in this collaborative fashion have not been previously reported. Pressure sore patients at the Harborview and University of Washington Medical Centers are evaluated by plastic surgery colleagues together with the Department of Physical Medicine and Rehabilitation. Patients believed to be candidates for complete postoperative rehabilitation are offered surgical repair and constitute this study cohort. Individuals who cannot cooperate with our protocol are treated nonoperatively and are not included in this study. A retrospective analysis of all 158 patients (mean age 34.5 years) operated on for 268 grade III and IV pressure sores between October of 1977 and December of 1989 was performed. Following surgical debridement and reconstruction, patients receive their principal medical care from the Department of Physical Medicine and Rehabilitation service while the Plastic Surgery Department manages the surgical wounds. Graduated patient mobilization is initiated in accord with a mutually agreed upon standardized protocol. New or primary sores numbered 174 (65 percent), and recurrent or secondary sores numbered 94 (35 percent). Mean patient follow-up was 3.7 years. The overall pressure sore recurrence rate (recurrence at the same site) was 19 percent, and the overall patient recurrence rate (previous patient developing a new sore) was 25 percent. Recurrence rates of 22 and 15 percent were noted for primary and secondary pressure sores, respectively. On most recent examination, 131 patients (83 percent) had intact pelvic and perineal skin. These results support a collaborative approach to the management of high-grade pressure sore patients. Our protocol of mutual patient evaluation followed by surgical reconstruction and postoperative rehabilitation yields notably low recurrence rates of both primary and secondary sores. In addition, the high percentage of patients who manifest long-term maintenance of skin integrity demonstrates the excellent education in personal skin and self-care that this approach provides. Not only do patients enjoy successful and durable reconstructive results, but additional hospitalizations and health care expenses implicit to pressure sore recurrence are consequently diminished. This collaborative clinical effort remains our standard of care.

Limb-salvage in reconstruction of recalcitrant pressure sores using the inferiorly based rectus abdominis myocutaneous flap.

Pressure sore closure is frequently a reconstructive challenge. This challenge is particularly evident in cases of multiply recurrent sores. In such settings, there are often opportunities to manage the recurrent wounds either by repeated advancement of previous flaps or by design of alternative ones. However, these interventions are not always feasible, and limb amputation with total thigh flap closure must be considered. A review of operative experience with seven such complex pressure sores in seven patients is presented. Each patient had previously suffered a permanent thoracic-level spinal cord injury. Prior attempts at wound closure were unsuccessful. Despite consideration of all described locoregional flaps, no limb-sparing procedure could be designed satisfactorily. As an alternative to either hip disarticulation and total thigh flap coverage or distant free-tissue transfer, we reconstructed the debrided ulcer beds with inferiorly based rectus abdominis myocutaneous flaps. Six of the seven wounds healed primarily, whereas one required repeated debridement and the addition of a gracilis muscle flap to achieve complete closure. Postoperative follow-up has ranged from 6 to 45 months. Each patient has returned to his baseline preoperative activity level with no clinical compromise of abdominal wall function. All wounds have healed. Successful application of the inferiorly based vertical rectus abdominis myocutaneous flap for cases of both recalcitrant ischial and trochanteric pressure sores is demonstrated and its consideration is advocated if no reconstructive options short of extremity amputation and total thigh flap coverage exist for such challenging sores.

Mild hypothermia during reperfusion reduces injury following ischemia of the rabbit ear.

Ischemia and reperfusion causes tissue injury that can be partially prevented by mild hypothermia. In this study we postulated that hypothermic protection could occur if imposed only during reperfusion. Rabbit ears were partially amputated, the central artery occluded for 6 h followed by reperfusion at an ambient temperature of either 20 or 24 degrees C resulting in ischemic ear temperatures of 22.5 vs. 24.7 degrees C. Ear temperature of rabbits remaining in the 24 degrees C room increased with reperfusion to 32.4 degrees C whereas those moved to the 20 degrees C room increased to 30.0 degrees C by 2 h of reperfusion. Ear volume was used as a measure of tissue edema and was measured for 7 days after the ears were allowed to reperfuse. Normalized myeloperoxidase content (polymorphonuclear cell accumulation) was significantly greater in the 24 degrees C ischemia-24 degrees C reperfusion group compared with the other groups. Ear edema was significantly less in the two groups exposed to 20 degrees C reperfusion compared with the 24 degrees C ischemia-24 degrees C reperfusion group. Peak ear volume was 5.0 times baseline for the 24 degrees C ischemia-24 degrees C reperfusion, 4.0 times baseline for the 20 degrees C ischemia-24 degrees C reperfusion, 3.4 times baseline for the 24 degrees C ischemia-20 degrees C reperfusion, and 3.3 times baseline for the 20 degrees C ischemia-20 degrees C group. We conclude that mild hypothermia reduces PMN accumulation and is more effective in preventing tissue injury when imposed during reperfusion compared with during ischemia.

Surgeon's role in the management of solitary renal cell carcinoma metastases occurring subsequent to initial curative nephrectomy: an institutional review.

BACKGROUND: Solitary metastases from a primary renal cell carcinoma (RCC) occur in < 10% of patients with metastatic RCC. To date, the benefit of surgically resecting such apparently solitary lesions has not been well documented. MATERIALS AND METHODS: Forty-one patients (25 men, 16 women) with metastatic renal cell carcinoma treated by surgical excision of solitary metastases (1970-1990) were retrospectively reviewed. They comprised 9% of patients with metastatic hypernephroma seen during this period. All patients had undergone previous curative nephrectomy with a median disease-free interval of 27 months. Patients with skeletal, spinal cord, and lymph node metastases were excluded. RESULTS: Metastases were intrathoracic (n = 20), intracranial (n = 7), and intraabdominal or in the extrapleural chest wall soft tissue (n = 10). Three patients had metastases to the thyroid gland and one had a solitary metastasis to an index finger. Median follow-up was 3.2 years. Complete resection was possible in 36 patients (88%) with a single lesion excised in 23 of these 36 patients (64%). There was no operative mortality. Predicted survival from the date of complete resection of metastases was 77%, 59%, and 31% at 1, 3, and 5 years, respectively, with a median survival of 3.4 years. One patient is alive without evidence of recurrent tumor 93 months from the first of 12 complete surgical resections. Varying adjuvant therapy was used in 50% of the patients. An increased histological tumor grade of the metastatic lesion relative to the original RCC was the only significant prognostic indicator identified. Disease-free interval and number of resected lesions were not significantly associated with patient survival. CONCLUSION: A small fraction of renal cell carcinoma patients are candidates for potentially curative surgical resection of solitary metastatic lesions. Excision of such lesions may contribute to prolonged survival in selected instances.

B lymphocyte precursors and myeloid progenitors survive in diffusion chamber cultures but B cell differentiation requires close association with stromal cells.

The aim of this study was to investigate the relative contribution of direct contact with stromal cells v stromal cell-derived soluble mediators to the differentiation of B lymphocytes and cells from other hematopoietic lineages. This was investigated by making a comparison between hemopoietic cells grown in direct contact with stroma to those in diffusion chambers (DCs) placed over purified populations of stroma. The source of stromal cells was adherent layers from myeloid or lymphoid long-term bone marrow cultures that had been treated with mycophenolic acid, an antibiotic that depletes hemopoietic cells from the cultures but retains a functional stroma. The cells seeded into the chambers were fresh marrow cells that had been passed through two consecutive nylon wool columns to deplete cell populations capable of forming an adherent cell layer in vitro. DCs were placed in wells in which the adherent stroma, growing under myeloid or lymphoid conditions, was present. The results indicate that progenitors of granulocytes and macrophages survived and differentiated in DCs under myeloid culture conditions, as the number of cells and absolute number of CFU-GM increased over that present in the reseed population. These levels, however, were markedly less than in parallel cultures in which the cells were seeded directly onto stroma. Hematopoiesis in DCs placed over hemopoietically active stroma was not optimal, suggesting that factors were used by those hemopoietic cells closest to the stroma. A B lymphocyte precursor survived in DCs under myeloid but not lymphoid conditions, and its differentiation into B lymphocytes was dependent on close association with stromal cells; B lymphopoiesis initiated when cells from DCs grown under myeloid conditions were harvested from the chambers and seeded directly onto stroma initiated and maintained under lymphoid bone marrow culture conditions. B lymphopoiesis did not initiate if the DC from the myeloid conditions was left intact and placed directly over a lymphoid stromal cell layer in lymphoid conditions.