The data demonstrate that ACS injection considerably improves clinical signs and symptoms of OA. It remains to be determined whether ACS is disease-modifying, chondroprotective, or chondroregenerative.

The common strategies for the treatment of patients with orthopedic diseases do not address the underlying pathogenesis. Several biologically based, local therapies aiming to influence the cytokine imbalance are either in development or in the initial stages of clinical use. A method based on exposure of blood leukocytes to pyrogen-free surfaces (e.g. glass spheres) elicits an accumulation of anti-inflammatory cytokines, including interleukin-1 receptor antagonist, and several growth factors, including insulin-like growth factor-1, platelet-derived growth factor, and transforming growth factor-beta(1), in the liquid blood phase. Based on these observations, a new therapy using cell-free, autologous conditioned serum (ACS) from the incubation of whole blood with glass spheres was developed. The injection of ACS into affected tissue(s) has shown clinical effectiveness and safety in animal models and studies, as well as in human clinical studies, for the treatment of osteoarthritis, lumbar stenosis, disc prolapse, and muscle injuries.

The intraarticular administration/injection of ACS results in decreased bone tunnel widening after ACL reconstructive surgery.

Mutant-enriched PCR was applied to the detection of mutations at codons I 2 and I 3 of K-ras genes in the stools of patients with colorectal cancer. Mutations were analyzed in stool samples obtained prior to surgery. Resected tumor specimens were screened for K-ras mutations by PCR-mediated RFLP analysis. Using normal stool samples, assay conditions were adjusted to optimal sensitivity and specificity. The following specimens were included in the stu* 16 stool samples corresponding to carcinomas in which K-ras mutations had bean identified; 7 randomly selected stool samples corresponding to carcinomas which were negative for K-ras mutations; I stool sample from a patient with non-Hodgkin's lymphoma. In 13 of the 16 stool samples (81%) corresponding to tumors in which K-ras mutations had been identified previously, K-ras mutations were detected. In 2 of the 7 stool samples corresponding to tumors in which K-ras mutations had not been detected by previous PCR-mediated RFLP analysis, K-ras mutations were also present Reanalyses of the tumors corresponding to these 2 positive stool samples by mutant-enriched PCR revealed a K-ras mutation in one of the tumors. The stool and tumor of the patient with non-Hodgkin's lymphoma were negative for K-ras mutations. DNA sequence analysis revealed that, for each of the K-ras mutations identified in stool samples, identical base substitutions were present in the corresponding tumor tissue. The results indicate that tumor cells harboring K-ras mutations can be detected in the stools of patients with colorectal cancer by mutant-enriched PCR with high sensitivity and specificity. Because of the simplicity of the technique, it may be suitable for screening of stool samples for mutations of the K-ros gene. 8 1996 Wiley-Liss, Inc.

The possibility of controlling the harmful intraarticular influence of elevated interleukin (IL)-1β synovial fluid concentration after anterior cruciate ligament (ACL) surgery could be useful. We investigated the correlation between serum and synovial fluid IL-1β levels following ACL reconstruction. We measured IL-1β concentration periodically in three synovial fluid and four serum samples in each of 20 patients receiving either autologous conditioned serum (ACS) containing endogenous anti-inflammatory cytokines including IL-1Ra and several growth factors (group A) or placebo (group B). A decrease in IL-1β synovial fluid concentration appeared to be more pronounced in absolute terms in group A. In eight patients serum IL-1β was detected on the 6th postoperative day. In four of them whose synovial fluid levels were over 10 pg/ml on the 6th postoperative day, serum IL-1β was detected on the 10th postoperative day. The results were different in group B. Correlation between serum and synovial fluid IL-1β appearance persists in patients after ACL surgery and ACS application. This study is an example of ACS influence on the ACL healing process controlling the IL-1β levels on the basis of the serum IL-1β detection.

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Abstract:The objectives of osteoarthritis (OA) management are to reduce pain and inflammation, slow cartilage degradation, improve function and reduce disability. Current strategies for managing knee OA include nonpharmacological interventions, oral pharmacological treatments, localized intra-articular injections, and surgery. It has become evident that the inflammatory response is a key contributor to the development and progression of knee OA. Signaling pathways involving growth factors and cytokines are being investigated for the development of new therapies that target the underlying biological processes causing the disease. This concept of 'molecular orthopedics' enables more patient-centered diagnostic and treatment strategies. In contrast to other conservative therapies, which ultimately only address OA symptoms, intra-articular injections, in particular autologous conditioned serum (ACS), provide benefits that have the potential to outweigh those of established pharmacological treatments and surgery. Surgery has historically been considered the final solution for treatment of knee OA, both by treating physicians and by patients; however, there are increasing concerns regarding the lack of randomized clinical trials providing evidence to support this opinion. Intra-articular injection of ACS has demonstrated efficacy as a treatment for knee OA in a number of studies, with a very low rate of adverse events and side effects, compared with surgery. Treatment with ACS utilizes the release of anti-inflammatory cytokines and regenerative growth factors to support the natural healing processes in the knee, and has the potential to provide a valuable alternative to surgical intervention.

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