The complement system in renal homograft recipients

The whole serum complement and its components were studied in 24 recipients of 27 renal homografts. In 12 of 13 instances in which homograft rejection was diagnosed, it was accompanied by significant declines in CH50, IA50, C4, and C3 levels, and to a lesser degree in C1 and C2 levels. Fourteen patients had normal graft function during the postoperative course of study, and in 13 of the 14 the complement levels were within the normal range throughout. In two recipients with systemic lupus erythematosus, very low initial complement levels increased to normal levels following removal of the native kidneys, splenectomy, and the provision of a well-functioning homograft. Anticomplement activity and elevated titers of C1 and C3 inactivators were observed in some patients, but these did not correlate with the changes in CH50. The findings confirm that the complement system participates in renal homograft rejection. © 1972

Modification of hyperacute canine renal homograft and pig-to-dog heterograft rejection by the intra-arterial infusion of citrate

Hyperacute rejection was studied in seven presensitized canine recipients of renal homografts and in 22 canine recipients of pig kidneys. Under both experimental circumstances, untreated animals rejected the grafts within a few minutes. With the intra-arterial infusion of sodium citrate, hyperacute heterograft rejection was forestalled for the duration of therapy, and with homografts the benefit outlasted treatment by many hours. The protection of heterografts was not due solely to anticoagulation by the citrate, since heparin in large doses did not accomplish the same thing. A contributory factor may have been complement inhibition since removal of complement by the grafts was greatly reduced in the citrate-treated animals. © 1971

Pseudo-arthrosis repair of a posterior cruciate ligament avulsion fracture

A pseudo-arthrosis repair of a 4-year-old bony avulsion fracture of the PCL using a minimally invasive technique, screw fixation, and bone grafting is reported. The case presented seems to be rather unique due to the fragment size and the approach for pseudo-arthrosis repair. There was a good functional result following minimally invasive pseudo-arthrosis repair of a posterior cruciate ligament avulsion fracture. There are no previous reports of similar pseudo-arthrosis repairs, and other authors report good results of delayed refixation of PCL avulsion fractures. Therefore, refixation and pseudo-arthrosis repair should be considered as a viable treatment

International Veterinary Epilepsy Task Force recommendations for a veterinary epilepsy-specific MRI protocol

Epilepsy is one of the most common chronic neurological diseases in veterinary practice. Magnetic resonance imaging (MRI) is regarded as an important diagnostic test to reach the diagnosis of idiopathic epilepsy. However, given that the diagnosis requires the exclusion of other differentials for seizures, the parameters for MRI examination should allow the detection of subtle lesions which may not be obvious with existing techniques. In addition, there are several differentials for idiopathic epilepsy in humans, for example some focal cortical dysplasias, which may only apparent with special sequences, imaging planes and/or particular techniques used in performing the MRI scan. As a result, there is a need to standardize MRI examination in veterinary patients with techniques that reliably diagnose subtle lesions, identify post-seizure changes, and which will allow for future identification of underlying causes of seizures not yet apparent in the veterinary literature. There is a need for a standardized veterinary epilepsy-specific MRI protocol which will facilitate more detailed examination of areas susceptible to generating and perpetuating seizures, is cost efficient, simple to perform and can be adapted for both low and high field scanners. Standardisation of imaging will improve clinical communication and uniformity of case definition between research studies. A 6–7 sequence epilepsy-specific MRI protocol for veterinary patients is proposed and further advanced MR and functional imaging is reviewed

Investigation into the Role of Tumor-Associated Macrophages in the Antitumor Activity of Doxil

Purpose. Our recent studies show specific localization of long-circulating liposomes (LCL) within the endosomal/lysosomal compartment of tumor-associated macrophages (TAM). Based on this finding, the present study aims to investigate whether clinically applied LCL formulations such as Doxil (LCLencapsulated doxorubicin), have alternative mechanisms of action additionally to direct drug-mediated cytotoxicity towards tumor cells. Methods. The antitumor activity of Doxil was evaluated in B16.F10 melanoma-bearing mice, in the presence and in the absence of TAM. To suppress TAM functions, liposomal clodronate (Lip-CLOD) was injected 24 h before the actual treatment. The effect of Doxil on the levels of angiogenic factors was determined using an angiogenic protein array. As positive control, the same experiments were conducted with LCL-encapsulated prednisolone phosphate (LCL-PLP), a tumor-targeted formulation with known strong anti-angiogenic/anti-inflammatory effects on TAM. Results. Our results show that the antitumor efficacy of Doxil was only partially attributed to the inhibition of TAM-mediated angiogenesis whereas LCL-PLP inhibited tumor growth through strong suppressive effects on pro-angiogenic functions of TAM. As described previously, the main mechanism of Doxil might be a cytotoxic effect on tumor cells. Conclusions. Our findings suggest that the antitumor activity of Doxil does not depend mainly on the presence of functional TAM in tumors

Malignant melanoma and bone resorption

The cellular and humoral mechanisms accounting for osteolysis in skeletal metastases of malignant melanoma are uncertain. Osteoclasts, the specialised multinucleated cells that carry out bone resorption, are derived from monocyte/macrophage precursors. We isolated tumour-associated macrophages (TAMs) from metastatic (lymph node/skin) melanomas and cultured them in the presence and absence of osteoclastogenic cytokines and growth factors. The effect of tumour-derived fibroblasts and melanoma cells on osteoclast formation and resorption was also analysed. Melanoma TAMs (CD14+/CD51−) differentiated into osteoclasts (CD14−/CD51+) in the presence of receptor activator for nuclear factor κB ligand (RANKL) and macrophage-colony stimulating factor. Tumour-associated macrophage-osteoclast differentiation also occurred via a RANKL-independent pathway when TAMs were cultured with tumour necrosis factor-α and interleukin (IL)-1α. RT–PCR showed that fibroblasts isolated from metastatic melanomas expressed RANKL messenger RNA and the conditioned medium of cultured melanoma fibroblasts was found to be capable of inducing osteoclast formation in the absence of RANKL; this effect was inhibited by the addition of osteoprotegerin (OPG). We also found that cultured human SK-Mel-29 melanoma cells produce a soluble factor that induces osteoclast differentiation; this effect was not inhibited by OPG. Our findings indicate that TAMs in metastatic melanomas can differentiate into osteoclasts and that melanoma fibroblasts and melanoma tumour cells can induce osteoclast formation by RANKL-dependent and RANKL-independent mechanisms, respectively