Acute Cellular Rejection Predominated by Monocytes Is a Severe Form of Rejection in Human Renal Recipients With or Without Campath-1H (Alemtuzumab) Induction Therapy

Campath-1H has been used successfully for induction and has resulted in a low rate of acute cellular rejection (ACR) in renal transplantation in combination with various postoperative immunosuppression regimens. This study was undertaken to investigate the extent of monocyte involvement in ACR, with or without Campath-1H induction. We found that monocytes represented the majority of inflammatory cells in grades Ib or higher ACR, but not with Ia type of ACR, regardless of the status of Campath-1H induction. Cases of ACR, following Campath-1H induction, appear to demonstrate a 'pure form' of monocytic ACR, whereas monocytes were mixed with many other types of inflammatory cells in the cases of ACR in the absence of Campath-1H induction. In addition with Campath-1H induction, the cases of monocyte-predominant ACR were found to uniformly exhibit a good response to corticosteroid treatment. We conclude that monocyte-predominate ACR may represent a severe form of rejection, with or without Campath-1H treatment.     

The use of coaxially aligned freeze-thawed skeletal muscle autografts in the repair of the cauda equina — in the sheep

Summary The aim was to develop a model for study of nerve regeneration in nerve roots above the level of the dorsal root ganglion and to investigate the use of freeze-thawed muscle autografts for repair of nerve roots at this level.Four adult sheep were used for the experiment. A laminectomy was performed at the lumbosacral junction and the S2 root identified. Both the dorsal and ventral S2 roots were divided unilaterally within the dura and a freeze-thawed muscle graft was inserted into the nerve gap.When assessed at 6 months an action potential was recordable from the ventral root in one sheep. Histological examination of the nerve roots showed evidence of regeneration across the graft in the ventral roots of all the sheep and the dorsal roots of some.This preliminary work indicates a capacity for regeneration of the cauda equina and that freeze-thawed muscle can support this. It provides a useful model for further study of nerve root repair.     

Surgical treatment of acne scarring by using skin grating knife

Summary A method of dermaplaning for acne scarring using a skin graft knife is described. This surgical technique cannot be considered as a form of dermabrasion. Its advantages are reported.     

Phenotype of endomyocardial biopsy-derived T-lymphocyte cultures and chronic rejection after heart transplantation

Chronic rejection (CR) is a major problem in long-term survival in heart transplantation. We analysed whether the occurrence of CR correlates with the incidence of acute rejections (AR) or with characteristics of endomyocardial biopsy-derived cell cultures. CR was diagnosed by annual angiography and defined as all coronary vascular changes. One year after transplantation 24 of the 63 patients had CR (38%). The incidence of AR in CR + and CR — patients was comparable. The patients in both groups had similar individual median percentages of EMB-yielding cell cultures. During the first year the CR — patients had more cultures in which at least 60% of the cells were CD4 + T cells (50% vs 37%, P = 0.05), due to a stronger CD4 predominance in the first 6 months. In the second year the CD4 predominance in the patients diagnosed as CR + after 1 year tended to be higher (P = 0.08). The patients had comparable percentages of cultures predominated by CD8 + T cells, γδ T cells or NK cells, irrespective of the time interval. These results might indicate that CD4 + T lymphocytes play a dual role in the aetiology of CR.     

Combined mortality and morbidity of direct surgical treatment of abdominal aortic aneurysm

Two hundred aneurysms of the abdominal aorta were treated surgically from 1980 to 1987 by the same surgeon. There were 187 men and 13 women whose mean age was 66.1 years. Nine patients were 80-years-old or more. Eighty-seven percent of patients had preoperative risk factors, 30% of which were coronary artery disease. The operative approach was through a transverse laparotomy in 188 patients compared to 11 midline incisions and one lumbotomy. An aortoaortic tube was inserted in 87 patients, a bifurcated prosthesis in 99, and a tube bypass in 14. Five patients (2.5%) died within the 30 day perioperative period. Death was due to colonic necrosis, right heart chamber thrombosis, renal failure after repeat operation for acute lower limb ischemia, and myocardial infarction associated with renal and respiratory failure. The morbidity rate was 15.7% (31 patients) and included seven neurologic accidents, four respiratory complications, five ischemic events of the lower limbs requiring reoperation and one amputation, four cardiac complications, two renal failures, one reversible colonic ischemia, one revision for incomplete hemostasis, one phlebitis, one sliding syndrome, and five minor infections or cutaneous complications. Mean duration of hospital stay was 10.9 days. These results confirm that direct operation on aortic aneurysms can be performed in patients from all age groups and even with associated diseases. A rapid, simple technique based on a transverse approach, minimal dissection and insertion of aortoaortic tubes, whenever feasible, appears to reduce combined mortality-morbidity.Presented at the Annual Meeting of the Societé de Chirurgie Vasculaire de Langue Française, May 20–21, 1988, La Grande Motte, France.     

Mice aorta loop grafting： A new model which separate vascular rejection and neointimal formation in chronic rejection

To study the cause and mechanism of transplantation vasculopathy which characterized by accelerated graft arteriosclerosis ( AGA), we estabfished a mouse aorta graft model. Methods: A segment of thoracic aortas of B10. A (2R) mice were transplanted to C57BL/10 mice abdominal aorta by end to side anastomoses. The different time point collected grafts were analyzed by morphological, histochemical and electro microscopic methods. Results:Rejection was manifested as a concentric progressive destruction of the smooth muscle cells. In contrast, the endothelial inflammation and subsequent ncointimal proliferation characteristic of AGA was localized to the regions of turbulent flow, i.e. the junction of the graft with the recipient aorta. Conclusion: This model separates the processes of rejec-tion and neointimal formation which usually manifested together in the lesion of AGA, elucidate that different mecha-nisms control vascular rejection and neointimal formation in chronic rejection.     

NK Cells Rapidly Reject Allogeneic Bone Marrow in the Spleen Through a Perforin- and Ly49D-Dependent, but NKG2D-Independent Mechanism

We have used a sensitive and specific in vivo killing assay to monitor the kinetics, anatomic location and mechanisms controlling NK-mediated rejection of Balb/c bone marrow by C57BL/6 natural killer (NK) cells. We find that NK killing of fully allogeneic bone marrow is a rapid, highly efficient process, leading to substantial rejection of transplanted marrow within 6 h of transplant and elimination of 85% of the transplanted cells within 2 days. NK-mediated rejection occurred predominantly in the spleen, with sparing of rejection in the bone marrow and lymph nodes. Rejection was dependent on Perforin gene function, but was independent of interferon-gamma. Finally, rejection of Balb/c bone marrow by B6 NK cells required signaling through the Ly49D receptor, but occurred despite blockade of NKG2D, which distinguishes these results from previous studies using semiallogeneic transplant pairs. These results identify NK cells as highly active mediators of bone marrow rejection, and suggest that inhibiting NK function early during transplantation may increase the efficiency of engraftment and allow successful engraftment of limiting doses of donor bone marrow.     

Granulysin: A Novel Host Defense Molecule

Granulysin is a novel cationic molecule present in the granules of cytotoxic T lymphocytes and natural killer cells. Cytotoxic T lymphocytes have long been associated with graft destruction in transplant rejection. Recent studies implicate granulysin in cell-mediated cytotoxicity, chemoattraction, immune activation and as a potential diagnostic biomarker for transplant rejection.     

Calcineurin Inhibitor Withdrawal from Sirolimus-Based Therapy in Kidney Transplantation: A Systematic Review of Randomized Trials

Calcineurin inhibitor (CNI) withdrawal has been used as a strategy to improve renal allograft function, however, it also carries risk of acute rejection. We conducted a systematic review of randomized trials that involved CNI withdrawal from a sirolimus-based immunosuppressive regimen. The search strategy yielded six trials (n = 1047 patients) reported in eight publications. CNI withdrawal from sirolimus-based therapy, was associated with an increased risk of acute rejection (risk difference, 6%; 95% CI 2-10%, p = 0.002) but a higher creatinine clearance (mean difference, 7.49 mL/min; 95% CI 5.08-9.89 mL/min, p < 0.00001) at 1 year compared to continued CNI and sirolimus therapy. Graft loss (relative risk, 0.87; 95% CI 0.46-1.64, p = 0.66) and death (relative risk, 0.88; CI 0.40-1.96, p = 0.76) were similar in both groups at 1 year. Hypertension was significantly reduced in the CNI withdrawal group (relative risk, 0.56; 95% CI 0.40-0.78, p = 0.0006). CNI withdrawal from sirolimus-based therapy is associated with an increased risk of acute rejection in the short term with a significant improvement in renal function and a reduction in hypertension. Longer follow-up is needed to determine if these changes will result in a significant improvement in patient and graft survival.