[Revision rate of periprosthetic joint infection post total hip or knee arthroplasty of 34 hospitals in China between 2015 and 2017: a multi-center survey].

Objective: To investigate the rate of periprosthetic joint infection (PJI) revision surgeries and clinical information of hip-/knee- PJI cases nationwide from 2015 to 2017 in China. Methods: An epidemiological investigation. A self-designed questionnaire and convenience sampling were used to survey 41 regional joint replacement centers nationwide from November 2018 to December 2019 in China. The PJI was diagnosed according to the Musculoskeletal Infection Association criteria. Data of PJI patients were obtained by searching the inpatient database of each hospital. Questionnaire entries were extracted from the clinical records by specialist. Then the differences in rate of PJI revision surgery between hip- and knee- PJI revision cases were calculated and compared. Results: Total of 36 hospitals (87.8%) nationwide reported data on 99 791 hip and knee arthroplasties performed from 2015 to 2017, with 946 revisions due to PJI (0.96%). The overall hip-PJI revision rate was 0.99% (481/48 574), and it was 0.97% (135/13 963), 0.97% (153/15 730) and 1.07% (193/17 881) in of 2015, 2016, 2017, respectively. The overall knee-PJI revision rate was 0.91% (465/51 271), and it was 0.90% (131/14 650), 0.88% (155/17 693) and 0.94% (179/18 982) in 2015, 2016, 2017, respectively. Heilongjiang (2.2%, 40/1 805), Fujian (2.2%, 45/2 017), Jiangsu (2.1%, 85/3 899), Gansu (2.1%, 29/1 377), Chongqing (1.8%, 64/3 523) reported relatively high revision rates. Conclusions: The overall PJI revision rate in 34 hospitals nationwide from 2015 to 2017 is 0.96%. The hip-PJI revision rate is slightly higher than that in the knee-PJI. There are differences in revision rates among hospitals in different regions.

The effect of BMP2/Smads pathway mediating platelet-rich fibrin on rat bone mesenchymal stem cells.

OBJECTIVE: We explored the influences on platelet-rich fibrin (PRF) to rat Bone Mesenchymal Stem Cells (BMSCs), as well as the role of bone morphogenetic protein 2 (BMP2)/maternal signal protein homolog (Smads) pathway. MATERIALS AND METHODS: The proposed research is approved by the ethics board of the Second Affiliated Hospital of Harbin Medical University. The BMSCs were isolated and purified. The BMSCs were assigned to a control group arbitrarily, PRF group, BMP activator group and BMP inhibitor group (hereinafter referred to as activator group and inhibitor group). Each group of BMSCs in the logarithmic growth phase was detected for the alkaline phosphatase (ALP) activity since 3 days and 14 days of culture; CCK-8 assay was conducted for detection of the proliferation of BMSCs; Real time PCR was conducted for detection of the osteogenic differentiation marker collagen I (COL-I), BMP2, Runt-related transcription factor 2(RUNX2), osteocalcin (OCN) mRNA relative expression levels; Western-Blot detection of BMP2, OCN, P-SMAD1/5/8, relative expression level of RUNX2 protein. RESULTS: In contrast to the control group, BMSCs' the ALP activity of the PRF group, activator group, as well as inhibitor group increased for 3 days and 14 days, and the activator group>PRF group>inhibitor group (p≤0.05). ALP activity in each group was elevated with the increase in culture time, the ALP activity of the control group, PRF group, activator group and inhibitor group increased (p≤0.05). In comparison to the control group, the relevant expression levels of COL-I, BMP-2, RUNX2 and OCN in the PRF group, activator group, and inhibitor group increased, and the activator group>PRF group>inhibitor group (p≤0.05). The relative expression levels of BMP2, OCN, p-SMAD1/5/8 and RUNX2 protein in each group were statistically different, the activator group>PRF group>control group>inhibitor group (p≤0.05). CONCLUSIONS: PRF can promote the proliferation and osteogenic differentiation of BMSCs by activating the BMP2/Smads signaling pathway.

[Hemodynamics-based analysis of factors associated with aneurysm rupture in different sides of the internal carotid artery].

Objective: To explore the influence of hemodynamics, morphological and clinical characteristics on rupture risk of the dorsal and non-dorsal internal carotid artery aneurysms (ICAAs). Methods: A total of 111 patients diagnosed with aneurysm by digital subtraction angiography (DSA) or surgery, underwent cranial CT angiography (CTA) were retrospectively collected from January 2010 to December 2016 at the Department of Diagnostic Radiology, Jinling Clinical College of Xuzhou Medical University (General Hospital of Eastern Theater Command). Among them, 41 were males and 70 were females, ranging in age from 32 to 83 (56±11) years old. The patients were divided into the ruptured group (n=54) and unruptured group (n=57) based on the hemorrhagic manifestation on non-enhanced CT images or DSA or surgery of the head. Demographics and the morphological characteristics of the aneurysms were evaluated. Hemodynamic parameters, including wall share stress, wall share stress gradient, and others were obtained in overall using computational fluid dynamics simulation technique. Characteristics were compared between the ruptured and unruptured groups. Logistic regression analysis was applied to evaluate the independent risk factors for rupture, and the hemodynamic characteristics associated with dorsal and non-dorsal aneurysms were analyzed, respectively. Results: Compared with the unruptured group, patients in the ruptured group were younger ((54.2±11.4) years and (58.3±9.9) years, P=0.033), mostly female (74.1% vs 52.6%, P<0.05), with a higher proportion of hypertension (46.3% vs 22.8%, P=0.009). The ruptured internal carotid artery aneurysms (ICAAs) were more frequently located at the dorsal of an arterial arch (57.4% vs 36.8%, P<0.05), and the flow of the blood was more complex, concentrated, unstable, and with a smaller impingement zone (68.5% vs 33.3%,55.6% vs 10.5%,72.2% vs 26.3% and 79.6% vs 36.8%, respectively, all P<0.05). Logistic regression demonstrated that women, hypertension, dorsal, concentrated flow pattern, and unstable flow pattern were an independent risk factors for ICAAs rupture [OR=3.551 (1.080-11.679), 3.900 (1.172-12.976), 4.966 (1.504-16.401), 51.893 (7.913-340.296) and 50.015 (8.423-296.985), respectively, all P<0.05]. The ruptured ICAAs located at non-dorsal had more concentrated, unstable, and with smaller impingement zone (P<0.05), while those at dorsal had more complex, concentrated, and unstable flow patterns, and with smaller impingement zone (all P<0.05). Conclusion: Women, hypertension, dorsal concentration, and unstable flow pattern are independent risk factors for the rupture of ICAAs. The dorsal locations of ICAAs could have a higher risk of rupture.

Use of 4+5 extensor compartmental vascularized bone graft and K-wire fixation for treating stage II-IIIA Kienböck's disease.

Vascularized bone grafts have shown favorable outcomes in Kienböck's disease, preventing the progression of lunate collapse and avascular necrosis. Here we describe our experience using a 4+5 extensor compartmental artery (ECA) vascularized bone graft combined with K-wire fixation. Between September 2010 and June 2013, 9 patients with Lichtman stage II-IIIA disease underwent arthroscopy prior to 4+5 ECA graft placement combined with temporary fixation (scaphocapitate and triquetrum-capitate joints). The average follow-up was 69 months (range, 51-92 months). Changes in pain, range of motion, grip strength, and pinch strength were analyzed. All patients had satisfactory recovery, especially pain relief and grip strength improvement (both P<0.01). Furthermore, magnetic resonance imaging follow-up was critical for monitoring lunate revascularization, especially in the early postoperative period.

Designing a 20 mm incision to protect the dorsal branch of the ulnar nerve during arthroscopic repair of triangular fibrocartilage complex injuries: Cadaver study and preliminary clinical results.

The ulnar-sided approach for arthroscopic peripheral triangular fibrocartilage complex (TFCC) repair may be associated with injury to the dorsal branch of the ulnar nerve (DBUN). The goal of this study was to develop a small incision to help minimize DBUN injury. Ten cadaveric upper limbs were used to measure the anatomic parameters of the DBUN. Based on these measured anatomical relationships, a 20 mm longitudinal incision with the ulnar styloid process as the midpoint was designed to explore and protect the DBUN. Three additional cadaveric upper limbs were used to test the feasibility of this method. Then this method was applied in 15 patients with TFCC injury (IB type). In 10 cadavers, the DBUN was located volar to the ulnar styloid process. The mean linear distance between the DBUN and the ulnar styloid process was 8.04 mm (range: 7.02-8.82mm) in the transverse-volar direction and 13.78 mm (range: 11.06-16.02mm) in the longitudinal-distal volar direction. In three additional cadavers, the DBUN was successfully explored and retracted with this incision, creating a safer space for passing sutures and tying knots. This modified method was used successfully in 15 patients, and the DBUN was protected during surgery. There were no complications, and most importantly, no injuries to the DBUN at the 6-month follow-up visit. Therefore, we recommend that a 20 mm longitudinal incision with the ulnar styloid process as the midpoint be made prior to passing sutures during the arthroscopic repair of TFCC tears to avoid injuring the various branches of the DBUN.

Association of TNFSF4 rs1234315, rs2205960 polymorphisms and systemic lupus erythematosus susceptibility: a meta-analysis.

BACKGROUND: The aim of this study was to explore the association between tumor necrosis factor superfamily number 4 (TNFSF4) rs1234315, rs2205960 polymorphisms and systemic lupus erythematosus (SLE) susceptibility. METHODS: A meta-analysis was performed on the association between rs1234315 and rs2205960 polymorphisms and SLE by allelic contrast, additive model, recessive model and dominant model. RESULTS: Regarding rs1234315 polymorphism, a total of five studies were included (6575 cases, 14,798 controls). Meta-analysis showed significant associations between the T allele and SLE in overall subjects and Asians (OR = 1.310, 95%CI: 1.104-1.553, p = 0.002; OR = 1.458, 95%CI: 1.328-1.602, p < 0.001). With respect to the rs2205960 polymorphism, significant associations between the T allele and SLE were found in all subjects (OR = 1.333, 95%CI: 1.254-1.418, p < 0.001), Asians (OR = 1.407, 95%CI: 1.345-1.471, p < 0.001) and Europeans (OR = 1.254, 95%CI: 1.185-1.328, p < 0.001). Results also showed significant associations between the additive model and SLE in all subjects and Asians (OR = 1.934, 95%CI: 1.500-2.494, p < 0.001; OR = 1.882, 95%CI: 1.318-2.689, p = 0.001). Furthermore, we detected significant associations between the dominant model and SLE in all subjects and Asians (OR = 1.421, 95%CI: 1.239-1.629, p < 0.001; OR = 1.297, 95%CI: 1.083-1.555, p = 0.005). Significant associations were found between the recessive model and SLE in overall subjects and Asians (OR = 1.677, 95%CI: 1.312-2.144, p < 0.001; OR = 1.751, 95%CI: 1.235-2.483, p = 0.002). CONCLUSION: The present study suggested that TNFSF4 rs1234315 and rs2205960 polymorphisms were associated with SLE susceptibility.

Silibinin alleviates inflammation and induces apoptosis in human rheumatoid arthritis fibroblast-like synoviocytes and has a therapeutic effect on arthritis in rats.

Silibinin, a natural polyphenolic flavonoid, possesses anti-oxidant, anti-inflammation and anti-cancer properties. The present study was designed to investigate the effects of silibinin on rheumatoid arthritis (RA) pathogenesis-related cells and collagen-induced arthritis (CIA) and further explore the potential underlying mechanisms. Our results showed that silibinin suppressed cell viability and increased the percentage of apoptotic RA-fibroblast-like synoviocytes (FLS). Furthermore, the production of inflammatory cytokines in RA-FLS and a CIA rat model was effectively inhibited by silibinin. Silibinin also induced macrophage M2 polarization in RAW264.7 cells. We further demonstrated that silibinin inhibits Th17 cell differentiation in vitro. The nuclear factor kappa B (NF-κB) pathway was suppressed in RA-FLS. In addition, Sirtuin1 (SIRT1) was decreased after silibinin treatment, and RA-FLS transfection with a short hairpin RNA (shRNA) of SIRT1 enhanced silibinin-induced apoptosis. Autophagy was markedly decreased in a dose-dependent manner following silibinin treatment. These findings indicate that silibinin inhibited inflammation by inhibiting the NF-κB pathway, and SIRT1 may participate in silibinin-induced apoptosis. Silibinin also inhibited autophagy in RA-FLS. Thus, silibinin may be a potential therapeutic agent for the treatment of RA.

High-free androgen index is associated with increased risk of non-alcoholic fatty liver disease in women with polycystic ovary syndrome, independent of obesity and insulin resistance.

BACKGROUND/OBJECTIVE: Central obesity and insulin resistance (IR) are common conditions in women with polycystic ovary syndrome (PCOS) and in subjects with non-alcoholic fatty liver disease (NAFLD). However, few studies have addressed the association between hyperandrogenism (HA) and NAFLD. We aimed to determine whether variations in the free androgen index (FAI) might be associated with NAFLD prevalence. SUBJECTS/METHODS: A cross-sectional study was performed including 400 Chinese women with PCOS and 100 age, and body mass index (BMI)-matched women. The anthropometric and serum biochemical parameters related to sex steroids, glucose and lipid profiles were examined. Liver fat content (LFC) was measured by quantitative ultrasound. RESULTS: The prevalence of NAFLD was 56.23% in PCOS patients and 38% in controls (P=0.001), and this prevalence increased with FAI quartile independently of obesity and homeostasis model assessment of insulin resistance (HOMA-IR). The FAI level increased from non-NAFLD group to NAFLD group. The FAI was positively associated with the metabolic parameters LFC, BMI, waist circumference, alanine aminotransferases, aspartate, triglyceride, total cholesterol and low-density lipoprotein cholesterol, and was negatively associated with high-density lipoprotein. Moreover, in multivariate logistic regression analysis BMI, high-sensitivity C-reactive protein (hsCRP), FAI, LFC and HOMA-IR were significantly associated with NAFLD. The cut-off values of FAI, LFC, BMI and hsCRP to predict NAFLD were 9.86%, 17.19%, 24.38% and 0.72%, respectively. The area under the curve for predicting NAFLD in PCOS patients showed comparable sensitivity and specificity between BMI and a new index combining FAI with hsCRP. CONCLUSIONS: A higher FAI level is associated with increased LFC and NAFLD prevalence independent of obesity and IR.

[Comparison of efficacy and safety between the anterior and the posterior approaches to total hip arthroplasty].

OBJECTIVE: To compare the efficacy and safety between direct anterior approach (DAA) and posterior approach (PA) in total hip arthroplasty. METHODS: This study evaluated postoperative results of 92 consecutive total hip arthroplasties performed by a single surgeon; 44 from the DAA, and 48 from PA. The age, body mass index, operation time, blood loss, hospital stay, positioning of the artificial hip, postoperative Harris score and postoperative complications were recorded and analyzed. RESULTS: Both the average age of the patients separately (58.0±11.9) years in DAA group and (61.0±10.4) years in PA group and the body mass index (25.1±3.7) in DAA group and (24.7±3.3) in PA group, showed no significant difference between the two groups. The DAA group had significantly reduced the hospital stay (3.8±1.7) days vs.(4.9±2.3) days for the PA group (P<0.05) and operation time was (76.0±17.4) min in DAA group, and (71.0±14.3) min in PA group (P>0.05). The amount of blood loss: in group DAA (238.0±55.3) mL, and in group PA (387.0±61.2) mL (P<0.05). There was no statistical difference in the positioning of the artificial hip: the cup anteversion in DAA group and PA group was 17.3°±5.3° vs. 18.6°± 5.1°, the cup inclination was 38.5°±5.7° vs. 37.7°±5.2°. In DAA group, there was significantly less use of assistive devices [(24.6±7.8) d vs. (31.7±10.2) d, P<0.05], and the pain was significantly lower. Harris score at the end of 6 weeks of the follow-up: in DAA group 85.7±5.4, and in PA group 81.3±6.1 (P<0.05); at the end of the last follow-up: in DAA group 93.4±4.7, and in PA group 92.3±5.3 (P>0.05). Complications were encountered in the two groups. There were two intraoperative complications (4.4%), 1 great trochanter fracture and 1 lateral cutaneous nerve injury in DAA group. No dislocation was observed in DAA group. One dislocations and 1 groin pain were recorded in PA group. No prosthesis loosening, deep vein thrombosis, sciatic nerve injury and other complications occurred in the two groups. CONCLUSION: Total hip arthroplasty using the anterior approach allows for superior recovery and better stability.

Regulatory role of B-cell maturation antigen on the toxic effect of chromium ions on human SaOS-2 osteoblasts.

Metal prostheses of artificial joints undergo wear, producing numerous metal particles and ions, such as Cr3+ . Cr3+ is considered a key factor leading to aseptic loosening. Many studies focus on the effect of Cr3+ on osteoblasts; however, little is known about the effect of Cr3+ on the B-cell maturation antigen (BCMA) in the osteoblasts. In this study, we first demonstrated the BCMA expressed in human SaOS-2 osteoblasts through reverse transcriptase-PCR, Western blot, and immunocytochemical analyses. Cr3+ decreased alkaline phosphatase (ALP), osteocalcin (OC), cell mineralization, and collagen type I mRNA and protein expression. Moreover, Cr3+ has an inhibitive effect on the expression of the BCMA in human SaOS-2 osteoblasts. However, after we upregulated the expression of the BCMA, ALP, OC, cell mineralization, and collagen type I mRNA and protein expression were increased. Overall, this study demonstrates that the BCMA is involved in human SaOS-2 osteoblast osteogenetic metabolism and plays a regulatory role on the toxic effect of chromium ions on human SaOS-2 osteoblasts.

Development of a Chinese version of the Western Ontario Meniscal Evaluation Tool: cross-cultural adaptation and psychometric evaluation.

BACKGROUND: The Western Ontario Meniscal Evaluation Tool (WOMET) is a questionnaire designed to evaluate the health-related quality of life (HRQOL) of patients with meniscal pathology. Our study aims to culturally adapt and validate the WOMET into a Chinese version. METHODS: We translated the WOMET into Chinese. Then, a total of 121 patients with meniscal pathology were invited to participate in this study. To assess the test-retest reliability, the Chinese version WOMET was completed twice at 7-day intervals by the participants. The construct validity was assessed using Pearson's correlation coefficient or Spearman's correlation to test for correlations among the Chinese version WOMET and the eight domains of Short Form-36 (SF-36), the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and the International Knee Documentation Committee (IKDC) score. Responsiveness was tested by comparison of the preoperative and postoperative scores of the Chinese version WOMET. RESULTS: The test-retest reliability of the overall scale and different domains were all found to be excellent. The Cronbach's α was 0.90. The Chinese version WOMET correlated well with other questionnaires which suggested good construct validity. We observed no ceiling and floor effects of the Chinese version WOMET. We also found good responsiveness for the effect size, and the standardized response mean values were 0.86 and 1.11. CONCLUSIONS: The Chinese version of the WOMET appears to be reliable and valid in evaluating patients with meniscal pathology.

Robotic phrenic nerve harvest: a feasibility study in a pig model.

The aim of this study was to report on the feasibility of robotic phrenic nerve harvest in a pig model. A surgical robot (Da Vinci S™ system, Intuitive Surgical(®), Sunnyvale, CA) was installed with three ports on the pig's left chest. The phrenic nerve was transected distally where it enters the diaphragm. The phrenic nerve harvest was successfully performed in 45 minutes without major complications. The advantages of robotic microsurgery for phrenic nerve harvest are the motion scaling up to 5 times, elimination of physiological tremor, and free movement of joint-equipped robotic arms. Robot-assisted neurolysis may be clinically useful for harvesting the phrenic nerve for brachial plexus reconstruction.

General effect of Sam68 on Rev/Rex regulated expression of complex retroviruses.

We have previously demonstrated that overexpression of Sam68 functionally substitutes for, as well as synergizes with, HIV-1 Rev in RRE-mediated gene expression and virus replication. In addition, C-terminal deletion mutants of Sam68 exhibit a transdominant negative phenotype in HIV replication. We now report that Sam68 also enhances the activities of Rev-like proteins of other complex retroviruses (e.g. HTLV-1 and EIAV) on their respective RNA targets. Furthermore, we demonstrate that Sam68 can function alone as well as synergize with Rev-MS2 and/or Rex-MS2 chimeric proteins on expression mediated by the corresponding RRE-MS2 fusion RNA element. Additionally, dominant negative mutants of Sam68 also repressed the synergistic activation of Sam68 with Rex, E-Rev, and/or Rev-MS2/Rex-MS2 on their corresponding RNA targets. Thus, Sam68 may play an important role in the post-transcriptional regulation of all complex retroviruses. Oncogene (2000) 19, 4071 - 4074

Expression of the BE-20 epididymal protein gene: in situ hybridization.

A protein designated as BE-20 was purified from cauda epididymal fluid of male rabbits and the amino acid sequence of the N-terminus was determined. A 23-mer oligonucleotide coding the N-terminal eight amino acids of the BE-20 protein was synthesized. The oligonucleotide was used as sense primer with rabbit epididymal mRNA as template in the RT-PCR system. The BE-20 cDNA consisted of 499 bp with an open reading frame of 285 bp encoding a deduced polypeptide composed of 95 amino acids. Digoxigenin-labeled BE-20 cDNA was prepared and used as a hybridization probe to detect the specific mRNA. The probe interacted with a 1.2-kb mRNA prepared from rabbit epididymis; mRNAs prepared from rabbit testis gave negative reaction. Using tissue sections, the BE-20 mRNA was located in the epithelial cells of the cauda epididymis and proximal segment of the ductus deferens by in situ hybridization method. Sections of the corpus and caput epididymis, testis, and liver gave negative reaction. Polyclonal anti-BE-20 antibodies were raised and found to inhibit in vitro the capacity of human sperm to penetrate zona-free hamster ova. The results suggest that BE-20 protein may influence maturation of spermatozoa during its movement through the epididymis and/or the capacity of sperm to fertilize ova.

Identification of a rabbit epididymal protein gene.

A protein designated as BE-20 was purified from cauda epididymal fluid of the rabbit by preparative polyacrylamide gel electrophoresis and HPLC on a mono Q HR5/5 anion exchange column. The purified protein migrated with an estimated Mt of 20,000 when analyzed by sodium dodecyl sulfate polyacrylamide gel electrophoresis. The amino acid sequence of the N-terminus of the BE-20 protein was determined. The initial eight amino acid residues were His-Gly-Ala-Asp-Lys-Pro-Gly-Val. The corresponding 23 mer oligonucleotide (5'-CATGGCGCTGACAAGCCTGGGGT-3') was synthesized and used as sense primer with rabbit epididymal mRNA as template in the RT-PCR system. The purified BE-20 cDNA consisted of 499 bp with an open reading frame of 285 bp encoding a deduced polypeptide composed of 95 amino acids. The BE-20 cDNA had 78.5% identity in 479 bp overlap with human epididymis-specific HE4 cDNA. The amino acid sequences of the initial 30 amino acid residues of the N-terminus of the purified protein and the deduced polypeptides were as follows: N-His-Gly-Ala-Asp-Lys-Pro-Gly-Val-Cys-Pro-Gln-Leu-Ser-Ala-Asp-Leu-Asn-Cy s- Thr-Gln-Asp-Cys-Arg-Ala-Asp-Gln-Asp-Cys-Ala-Glu. The deduced polypeptide contained 16 cysteine residues and had partial sequence homology with proteins belonging to the four-disulfide core family of extracellular proteinase inhibitors. The BE-20 protein may play a role in sperm maturation and/or capacitation.

Cytokines in chronic inflammatory arthritis. II. Granulocyte-macrophage colony-stimulating factor in rheumatoid synovial effusions.

A liquid culture technique was used to study 23 synovial fluids (SF) (21 from inflammatory joint diseases and 2 noninflammatory SF) and supernatants of two cultured rheumatoid arthritis (RA) synovial tissues for colony-stimulating factor (CSF). The proliferative responses of human peripheral blood macrophage-depleted non-T cells treated with synovial fluids, supernatants of synovial tissue explants, and recombinant granulocyte-macrophage (rGM)-CSF were compared. Aggregates of cells that formed in long-term cultures (15 d) were similar for each applied agent and consisted of macrophages, eosinophils, and large blasts. Tritiated thymidine incorporation was proportional to the concentration of rGM-CSF and was accompanied by an increase in number and size of cellular aggregates formed in the cultures. CSF activity was observed in inflammatory SF, with tritiated thymidine uptake of 3,501 +/- 1,140 cpm in the presence of RA samples (n = 15) compared to 1,985 +/- 628 for non-RA inflammatory SF (n = 7) (P less than 0.05) and 583 +/- 525 for medium (n = 6) (P less than 0.01). The proliferative response to RA SF was often more apparent when the samples were diluted, because at higher concentrations the RA SF was inhibitory. Two RA SF were fractionated by Sephadex G100 column chromatography; low levels of CSF activity were detected in fractions corresponding to Mr of 70-100 kD, but the major CSF activity was found in the 20-24-kD fractions. A polyclonal rabbit anti-GM-CSF antibody eliminated the stimulating activity from both rGM-CSF and RA SF. Finally, a specific RIA identified significant levels of GM-CSF (40-140 U/ml) in the culture supernatants of 3 additional RA synovial tissues. These data document the local production of GM-CSF in rheumatoid synovitis and are the first description of this cytokine at a site of disease activity.

Cytokines in chronic inflammatory arthritis. I. Failure to detect T cell lymphokines (interleukin 2 and interleukin 3) and presence of macrophage colony-stimulating factor (CSF-1) and a novel mast cell growth factor in rheumatoid synovitis.

Because previous studies showed low levels of IFN-gamma in rheumatoid arthritis (RA) synovial fluid (SF) and synovial tissue (ST) explant supernatants, we assayed RA SF and ST for IL-2 and IL-3-like activity. Using an IL-2 dependent murine CTLL line, 6 of 14 RA SF caused increased thymidine uptake (greater than three times control). The activity was distinct from IL-2 because it was not blocked by antibody to IL-2-R. In addition, IL-2 was not detected (less than 50 pg/ml) in 16 joint samples using an ELISA. Multi-colony-stimulating factor (CSF) activity was measured using two assays that can detect murine IL-3 (mast cell proliferation, and bone marrow CSF). In the mast cell assay, [3H]TdR uptake was 493 +/- 67 cpm for medium, 2,910 +/- 329 cpm in the presence of RA SF (p less than 0.001), 1,246 +/- 156 cpm in the presence of SF from patients with seronegative spondyloarthropathies (p less than 0.001), and 736 +/- 100 cpm in the presence of osteoarthritis SF (p greater than 0.1). In the CSF assay, four of five RA SF and five of five RA ST induced colony formation from bone marrow nonadherent cells. Macrophage colonies were most common, although mixed colonies and granulocytes were occasionally observed. The multi-CSF activity in RA is not due to IL-3 since human rIL-3 was not active in either murine assay, and IL-3 mRNA was not detected in RA synovium. Sephadex column chromatography of RA SF revealed that the mast cell growth factor (approximately 6 x 10(3) mol wt) and the CSF (approximately 40 and 100 x 10(3) mol wt) are distinct. The colony-stimulating aspect of the "IL-3-like" activity in RA SF is likely due to CSF-1 because it is the appropriate mol wt and because the activity was neutralized by specific anti-CSF-1 antibody. Finally, an RIA detected 1.6-25 ng/ml of CSF-1 in RA SF and ST and CSF-1 mRNA was detected in four of five RA synovial tissue samples tested.

Spinal stenosis with meralgia paraesthetica.

Of 232 patients with evidence of lumbar spinal stenosis, 13 had symptoms of meralgia paraesthetica. Myelography demonstrated that in all but one of these 13 cases the L3-4 level was involved by stenosis; in 12 matched control patients with spinal stenosis, none had involvement at this level. We found that both the ligamentum flavum and the laminae at L3-4 level were thicker than in a control group. Decompressive laminectomy at the L3-4 level significantly reduced the area of hypo-aesthesia in the thigh, effecting complete cure in seven of the 11 cases. Meralgia paraesthetica is not uncommon in patients with spinal stenosis and is referable to changes at the L3-4 level. It seems that many cases of meralgia may have a spinal origin.