Synovial fluid interleukin-16, interleukin-18, and CRELD2 as novel biomarkers of prosthetic joint infections.

OBJECTIVES: Prosthetic joint infection (PJI) diagnosis is a major challenge in orthopaedics, and no reliable parameters have been established for accurate, preoperative predictions in the differential diagnosis of aseptic loosening or PJI. This study surveyed factors in synovial fluid (SF) for improving PJI diagnosis. METHODS: We enrolled 48 patients (including 39 PJI and nine aseptic loosening cases) who required knee/hip revision surgery between January 2016 and December 2017. The PJI diagnosis was established according to the Musculoskeletal Infection Society (MSIS) criteria. SF was used to survey factors by protein array and enzyme-linked immunosorbent assay to compare protein expression patterns in SF among three groups (aseptic loosening and first- and second-stage surgery). We compared routine clinical test data, such as C-reactive protein level and leucocyte number, with potential biomarker data to assess the diagnostic ability for PJI within the same patient groups. RESULTS: Cut-off values of 1473 pg/ml, 359 pg/ml, and 8.45 pg/ml were established for interleukin (IL)-16, IL-18, and cysteine-rich with EGF-like domains 2 (CRELD2), respectively. Receiver operating characteristic curve analysis showed that these factors exhibited an accuracy of 1 as predictors of PJI. These factors represent potential biomarkers for decisions associated with prosthesis reimplantation based on their ability to return to baseline values following the completion of debridement. CONCLUSION: IL-16, IL-18, and CRELD2 were found to be potential biomarkers for PJI diagnosis, with SF tests outperforming blood tests in accuracy. These factors could be useful for assessing successful debridement based on their ability to return to baseline values following the completion of debridement.Cite this article: M-F. Chen, C-H. Chang, L-Y. Yang, P-H. Hsieh, H-N. Shih, S. W. N. Ueng, Y. Chang. Synovial fluid interleukin-16, interleukin-18, and CRELD2 as novel biomarkers of prosthetic joint infections. Bone Joint Res 2019;8:179-188. DOI: 10.1302/2046-3758.84.BJR-2018-0291.R1.

Hyperbaric oxygen inhibits the HMGB1/RAGE signaling pathway by upregulating Mir-107 expression in human osteoarthritic chondrocytes.

OBJECTIVE: MicroRNA (miRNA)107 expression is downregulated but high mobility group box 1 (HMGB-1), Toll-like receptors (TLRs), and receptor for advanced glycation end products (RAGE) are upregulated in osteoarthritic (OA) cartilage. We investigated mir-107/HMGB-1 signaling in OA after hyperbaric oxygen (HBO) treatment. DESIGN: MiR-107 mimic was transfected and the HMGB-1 was analyzed in OA chondrocytes. MiRNA targets were identified using bioinformatics and a luciferase reporter assay. After HBO treatment, the mRNA or protein levels of HMGB-1, RAGE, TLR2, TLR4, and inducible nitric oxide (NO) synthase (iNOS) and phosphorylation of mitogen-activated protein kinase (MAPK) were evaluated. The secreted HMGB-1 and matrix metalloproteases (MMPs) levels were quantified. Finally, we detected the HMGB-1 and iNOS expression in rabbit cartilage defects. RESULTS: Overexpression of miR-107 suppressed HMGB-1 expression in OA chondrocytes. The 3'UTR of HMGB-1 mRNA contained a 'seed-matched-sequence' for miR-107. MiR-107 was induced by HBO and a marked suppression of HMGB-1 was observed simultaneously in OA chondrocytes. Knockdown of miR-107 upregulated HMGB-1 expression in hyperoxic cells. HBO downregulated the mRNA and protein expression of HMGB-1, RAGE, TLR2, TLR4, and iNOS, and the secretion of HMGB-1. HBO decreased the nuclear translocation of nuclear factor (NF)-κB, downregulated the phosphorylation of MAPK, and significantly decreased the secretion of MMPs. Morphological and immunohistochemical observation demonstrated that HBO markedly enhanced cartilage repair and the area stained positive for HMGB-1 and iNOS tended to be lower in the HBO group. CONCLUSIONS: HBO inhibits HMGB-1/RAGE signaling related pathways by upregulating miR-107 expression in human OA chondrocytes.

Rheumatoid arthritis patients with hip fracture: a nationwide study.

SUMMARY: The study was to investigate the outcomes of rheumatoid arthritis (RA) patients with hip fractures with a large-scale, population-based, nationwide, case-cohort study using the Taiwan National Health Insurance database. The group has hip fractures at a younger age, higher complication, and mortality rate, which indicate that early intervention is necessary. INTRODUCTION: This study seeks to evaluate the incidence, mortality, and complication rates in RA patients with hip fractures, using a nationwide database. METHODS: Data were collected from the National Health Insurance Research Database of Taiwan. The study group included 117,129 patients with hip fractures diagnosed from January 2004 to December 2010. Matching based on the propensity of RA patients was used. In total, 1,088 hip fractures were reported among patients with RA. Patients with hip fractures were divided into two groups: those without RA (controls) and those with RA (RA group). The incidence of hip fracture and mortality and complication rates after the hip fracture were then compared between the two groups. RESULTS: RA patients had a significantly higher incidence of hip fracture (3,260/100,000 person-years) compared with the general population (72/100,000 person-years). Hip fractures occurred significantly earlier among RA patients (70.6±5.3 years) compared with the control group (76.1±6.2 years). Cumulative mortality rates at 6-month and 1-year follow-up were significantly higher among patients in the RA group (9.47 and 18.47%) compared to the controls (8.47 and 13.62%) and among RA patients without hip fractures (3.24 and 6.16%). There was a significantly higher incidence of osteomyelitis after hip fracture among the RA group than among the body mass index-, comorbidity-, age-, and sex-matched patients in the control group. CONCLUSIONS: Compared to patients without RA, those with RA have a higher incidence of hip fractures at a relatively younger age and with higher complication and mortality rates. Steroid and disease-modifying anti-rheumatic drugs, the most common medicine in Taiwanese RA patients, might contribute to the high incidence of fracture and post-op infection. Appropriate early intervention to prevent hip fractures in RA patients is a critical issue in rheumatology care.

Nationwide cohort study of hip fractures: time trends in the incidence rates and projections up to 2035.

SUMMARY: A growing elderly population is expected worldwide, and the burden of hip fractures on health care system will continue to increase. By 2035, there will be a 2.7-fold increase in the number of hip fractures in Taiwan. The study provides quantitative basis for the future distribution of medical resources. INTRODUCTION: Hip fractures have long been recognized as a major public health concern. The study aimed to determine time trends in the incidence of hip fractures and to forecast the number of hip fractures expected in Taiwan up to 2035. METHODS: A nationwide survey was conducted using data from the Taiwan National Health Insurance Research Database from 2004 to 2011. A total of 141,397 hip fractures were identified, with a mean of 17,675 fractures/year. Annual incidences of hip fractures were calculated and tested for trends. Projections of the incidence rates of hip fractures and bed days associated with hip fractures were calculated using Poisson regression on the historical incidence rates in combination with population projections from 2012 to 2035. RESULTS: The incidence rates of hip fracture during 2004-2011 were 317 and 211 per 100,000 person-years among women and men, respectively. Over this 8-year period, the age-standardized incidence of hip fracture decreased by 13.4% among women and 12.2% among men. Despite the decline in the age-standardized incidence, the absolute number of hip fractures increased owing to the aging population. The number of hip fractures is expected to increase from 18,338 in 2010 to 50,421 in 2035-a 2.7-fold increase. The number of bed days for 2010 and 2035 was estimated at 161,248 and 501,995, respectively, representing a 3.1-fold increase. CONCLUSIONS: The socioeconomic impact of hip fractures will be high in the near future. This study provides a quantitative basis for future policy decisions to serve this need.

Liquid antibiotics in bone cement: an effective way to improve the efficiency of antibiotic release in antibiotic loaded bone cement.

OBJECTIVES: The objective of this study was to compare the elution characteristics, antimicrobial activity and mechanical properties of antibiotic-loaded bone cement (ALBC) loaded with powdered antibiotic, powdered antibiotic with inert filler (xylitol), or liquid antibiotic, particularly focusing on vancomycin and amphotericin B. METHODS: Cement specimens loaded with 2 g of vancomycin or amphotericin B powder (powder group), 2 g of antibiotic powder and 2 g of xylitol (xylitol group) or 12 ml of antibiotic solution containing 2 g of antibiotic (liquid group) were tested. RESULTS: Vancomycin elution was enhanced by 234% in the liquid group and by 12% in the xylitol group compared with the powder group. Amphotericin B elution was enhanced by 265% in the liquid group and by 65% in the xylitol group compared with the powder group. Based on the disk-diffusion assay, the eluate samples of vancomycin-loaded ALBC of the liquid group exhibited a significantly larger inhibitory zone than samples of the powder or the xylitol group. Regarding the ALBCs loaded with amphotericin B, only the eluate samples of the liquid group exhibited a clear inhibitory zone, which was not observed in either the xylitol or the powder groups. The ultimate compressive strength was significantly reduced in specimens containing liquid antibiotics. CONCLUSIONS: Adding vancomycin or amphotericin B antibiotic powder in distilled water before mixing with bone cement can significantly improve the efficiency of antibiotic release than can loading ALBC with the same dose of antibiotic powder. This simple and effective method for preparation of ALBCs can significantly improve the efficiency of antibiotic release in ALBCs. Cite this article: Bone Joint Res 2014;3:246-51.

Gentamicin in bone cement: A potentially more effective prophylactic measure of infectionin joint arthroplasty.

OBJECTIVES: The objective of this study is to determine an optimal antibiotic-loaded bone cement (ALBC) for infection prophylaxis in total joint arthroplasty (TJA). METHODS: We evaluated the antibacterial effects of polymethylmethacrylate (PMMA) bone cements loaded with vancomycin, teicoplanin, ceftazidime, imipenem, piperacillin, gentamicin, and tobramycin against methicillin-sensitive Staphylococcus aureus (MSSA), methicillin-resistant Staph. aureus (MRSA), coagulase-negative staphylococci (CoNS), Escherichia coli, Pseudomonas aeruginosa, and Klebsiella pneumoniae. Standardised cement specimens made from 40 g PMMA loaded with 1 g antibiotics were tested for elution characteristics, antibacterial activities, and compressive strength in vitro. RESULTS: The ALBC containing gentamicin provided a much longer duration of antibiotic release than those containing other antibiotic. Imipenem-loading on the cement had a significant adverse effect on the compressive strength of the ALBC, which made it insufficient for use in prosthesis fixation. All of the tested antibiotics maintained their antibacterial properties after being mixed with PMMA. The gentamicin-loaded ALBC provided a broad antibacterial spectrum against all the test organisms and had the greatest duration of antibacterial activity against MSSA, CoNS, P. aeruginosa and E. coli. CONCLUSION: When considering the use of ALBC as infection prophylaxis in TJA, gentamicin-loaded ALBC may be a very effective choice. Cite this article: Bone Joint Res 2013;2:220-6.

The concentration of antibiotic in fresh-frozen bone graft.

We investigated the antibiotic concentration in fresh-frozen femoral head allografts harvested from two groups of living donors. Ten samples were collected from patients with osteoarthritis of the hip and ten from those with a fracture of the neck of the femur scheduled for primary arthroplasty. Cefazolin (1 g) was administered as a pre-operative prophylactic antibiotic. After storage at -80 degrees C for two weeks the pattern of release of cefazolin from morsellised femoral heads was evaluated by an in vitro broth elution assay using high-performance liquid chromatography. The bioactivity of the bone was further determined with an agar disc diffusion and standardised tube dilution bioassay. The results indicated that the fresh-frozen femoral heads contained cefazolin. The morsellised bone released cefazolin for up to four days. The concentration of cefazolin was significantly higher in the heads from patients with osteoarthritis of the hip than in those with a fracture.Also, in bioassays the bone showed inhibitory effects against bacteria.We concluded that allografts of morsellised bone from the femoral head harvested from patients undergoing arthroplasty of the hip contained cefazolin, which had been administered pre-operatively and they exhibited inhibitory effects against bacteria in vitro.

Elevated intraosseous pressure in the intertrochanteric region is associated with poorer results in osteonecrosis of the femoral head treated by multiple drilling.

Multiple drilling is reported to be an effective treatment for osteonecrosis of the head of femur, but its effect on intra-osseous pressure has not been described. We undertook multiple drilling and recorded the intra-osseous pressure in 75 osteonecrotic hips in 60 patients with a mean age of 42 years (19 to 67). At a mean follow-up of 37.1 months (24 to 60), 42 hips (56%) had a clinically successful outcome. The procedure was effective in reducing the mean intra-osseous pressure from 57 mmHg (SD 22) to 16 mmHg (SD 9). Hips with a successful outcome had a mean pressure of 26 mmHg (SD 19). It was less effective in preventing progression of osteonecrosis in hips with considerable involvement and in those with a high intra-osseous pressure in the intertrochanteric region (mean 45 mmHg (SD 25)). This study is not able to answer whether a return of the intra-osseous pressure to normal levels is required for satisfactory healing.

Involvement of Gas7 along the ERK1/2 MAP kinase and SOX9 pathway in chondrogenesis of human marrow-derived mesenchymal stem cells.

OBJECTIVE: The growth-arrest-specific protein, Gas7, has been shown to be involved in reorganization of the cytoskeleton and for inducing changes in cell shape during cell differentiation. The goals of this study were to investigate the novel role of human Gas7 (hGas7) in chondrogenic differentiation of human mesenchymal stem cells (hMSCs) and to identify the relationship between hGas7, extracellular signal-regulated kinase (ERK1/2) and SOX9 in the chondrogenic pathway. METHODS: Bone marrow-derived hMSCs were induced to undergo chondrogenic differentiation with transforming growth factor-beta1 (TGF-beta1) in an aggregate culture system. The expression of hGas7 and SOX9 and phosphorylation of ERK1/2 at multiple time points were investigated. Chondrogenic capacity was evaluated by the size of aggregates, by glycosaminoglycan content, and by type II collagen and proteoglycan deposition after interfering with expression of hGas7, ERK1/2 or SOX9. To delineate the functional role of these genes in chondrogenesis, inhibition of individual gene's expression in hMSCs, by antisense oligonucleotides or interference RNA (siRNA), and the effect on chondrogenic differentiation were also investigated. RESULTS: Treatment of hMSCs with TGF-beta1 resulted in a transient up-regulation of hGas7b, one of the hGas7 isoforms (day 3-day 5), a transient phosphorylation of ERK1/2 (0.5-4 h) and an up-regulation of SOX9 (2 h to day 14). Transient expression of hGas7b was also detected in hMSCs by reverse transcription-polymerase chain reaction at day 2 and day 3 following TGF-beta1 treatment. Interference with hGas7b production by hGas7b-specific antisense oligonucleotide or inhibition of p-ERK with PD98059, a specific inhibitor of ERK signaling pathway, or interference with SOX9 production by SOX9 siRNA all caused adverse effects of chondrogenic differentiation of hMSCs. Meanwhile, inhibition of p-ERK or SOX9 both blocked the expression of hGas7b. However, the p-ERK and SOX9 pathway was not affected by inhibition of hGas7b. CONCLUSION: These results provide evidence that the transient expression of hGas7b, regulated by activation of ERK1/2 and SOX9 pathway, is essential for chondrogenic differentiation of hMSCs.

Effects of hyperbaric oxygen and platelet derived growth factor on medial collateral ligament fibroblasts.

PURPOSE: This study investigated hyperbaric oxygen (HBO2) and platelet-derived growth factor-BB (PDGF-BB) to determine their combined effects on fibroblasts from rabbit medial collateral ligament (MCL). METHOD: Cells were divided into four groups: (I) Control, (II) HBO2 treatment, (III) PDGF-BB treatment and (IV) HBO2 combined with PDGF-BB treatment. All hyperoxic cells were exposed to 100% O2 at 2.5 atmospheres absolute (ATA) in a hyperbaric chamber for 120 minutes per 48 hours. Measurement of cell growth was based on increase in cell number. Cell cycle modulations were analyzed by fluorescence-activated cell sorter (FACS). Quantity of Type I and Type III collagen was determined by western blotting and image analyzer. RESULTS: Treatment doses of HBO2 alone or PDGF-bb alone dependently increased cell growth. A combination of HBO2 treatment plus PDGF-bb treatment had an additive effect on cell growth in comparison with HBO2 treatment alone or PDGF-bb treatment alone. FACS analysis revealed that HBO2 alone, PDGF-bb alone and PDGF-bb plus HBO2 treatment increase the percentage of cells accumulated in S-phase. Western blotting analysis revealed that Type III collagen content was decreased significantly after HBO2 treatment alone or HBO2 plus PDGF-bb treatment but not in PDGF-bb treatment alone. In contrast, although Type I collagen content was increased after HBO2 treatment, the increase in Type I collagen (increase /original) was not statistically significant. CONCLUSION: HBO2 or HBO2 plus PDGF-bb treatment decreases the Type III collagen/Type I collagen content, which could result in mechanically stronger collagen fibrils. We propose HBO2 therapy as a potentially effective treatment for MCL healing.

Two-incision total hip replacement: Intra-operative fluoroscopy versus imageless navigation for cup placement.

The purpose of this study was to describe the surgical technique and to investigate results of a modified two-incision total hip replacement using either intraoperative fluoroscopy or imageless navigation. Twenty-nine patients (30 hips) with a minimum follow-up of one year were enrolled in this study. The patients were evaluated at 3, 6, 12 weeks, 6 months, and 1-year. The functional recovery as represented by the Harris hip score and WOMAC scale were better in the fluoroscopy group of patients at the early postoperative stage (3 wks). Thereafter, both groups showed rapid recovery with no difference in scores. Injury to the lateral femoral cutaneous nerve was the most commonly seen complication and it occurred in 6 hips (fluoroscopy 2; imageless 4). The symptoms were transient and resolved in 6 months in all 6 cases. This study demonstrated that the role of intraoperative fluoroscopy could safely be replaced by an imageless navigation system for the MIS-2 THA.

Inhibition of nitric oxide can ameliorate apoptosis and modulate matrix protein gene expression in bacteria infected chondrocytes in vitro.

Bacterial infection stimulates nitric oxide (NO) production in chondrocytes. However, the role of NO in chondrocyte apoptosis after infection remains unclear. The purpose of the study was to test if inhibition of NO could ameliorate apoptosis and modulate matrix protein gene expression in bacteria-infected chondrocytes. It was shown that pre-treating chondrocytes with L-NAME (1 mM) significantly decreased the release of NO (from 72 to 14 microM) and the extent of apoptosis (from 52.9% to 18.9%). Pre-treatment with L-NAME also counteracted the bacteria-induced downregulation of Type II collagen (from 26% to 79%) and aggrecan (from 63% to 105%) mRNA levels. Inhibition of NO after the induction of infection could not decrease the extent of apoptosis and modulate matrix protein gene expression. The results of this study support the hypothesis that NO has an important role in bacteria-induced chondrocyte apoptosis. Pre-treatment but not post-treatment could ameliorate the extent of apoptosis and reestablish the cartilage matrix protein gene expression. This study suggests that in addition to NO, other mechanisms may be responsible for the sustained destruction of articular cartilage in the post-infectious arthropathy.

Signal transduction pathways and apoptosis in bacteria infected chondrocytes.

The mechanism underlying chronic destructive arthropathy after pyogenic arthritis is not clear. This study evaluated the role of apoptosis in Staphylococcus aureus infected human articular chondrocytes and investigated the signal transduction pathways activated by bacterial infection. Chondrocytes cultured in monolayer were challenged with bacteria for 6 h and were analyzed after incubation for 2, 18, and 24 h. Chondrocytes showed morphologic and biochemical evidences of apoptosis after infection and the following incubation period. Although treatment with extensive washing and vancomycin could ameliorate the amount of apoptosis from 31% to 15% at 2 h, from 48% to 23% at 18 h, and from 58% to 33% at 24 h, the infected samples with treatment still had higher amount of apoptosis than the un-infected controls (ANOVA P < 0.001). Accompanying with the increasing amount of apoptosis, the caspase activity was upregulated in bacteria infected samples and remained high in samples with treatment (ANOVA P < 0.05). Signal transduction pathways activated by bacterial infection were assessed by co-transfection technique. After infection, the c-Jun N-terminal kinase, extracellular signal-regulated kinase, and cyclic AMP-dependent protein kinase activities were elevated by 7.6-, 7.3-, and 3.2-fold, respectively, compared to the uninfected controls. The data support the hypothesis that human chondrocytes will undergo apoptosis after infection by a single organism. Apoptosis and activated intracellular kinase activities may be related to the pathogenesis of post-infectious destructive arthropathy.

Surgical treatment for pathological long bone fracture in patients with multiple myeloma: a retrospective analysis of 22 cases.

BACKGROUND: The purpose of this study was to retrospectively review the cases of pathologic long bone fractures caused by multiple myeloma treated in our hospital, to analyze the surgical method, complications, radiation therapy, survival time, and influence on quality of life. METHODS: In a retrospective study, 22 patients with the pathological long bone fractures due to multiple myeloma who were surgically treated between 1987 and 1997 were analyzed. All patients received open reduction and internal fixation either with plates or intra-medullary nailing. Cement augmentations were performed in the majority of cases (91%). A detailed retrospective analysis was done to correlate the surgical methods, radiation therapy, functional results, and complications post-surgically. RESULTS: The most common site of fracture was the femur. The mean postoperative survival time was around 19 months. Post-operative pain relief was satisfactory, and only two patients required narcotics. No major complications were observed. However the union rate was only 30%, which might have been due to the inhibitory effect of radiation therapy on bone healing, or insufficient osteogentic ability of the myeloma-involved bone. CONCLUSION: Satisfactory pain relief and low implant failure rate was achieved and no definite evidence of tumor dissemination was found in this study. The authors suggest that open reduction and internal fixation with cement augmentation is a favorable treatment option for those patients suitable for surgery. However, postoperative radiation therapy may be associated with a low rate of union.

Two-staged revision total hip arthroplasty due to Salmonella infection: case report.

Salmonella infection of a hip prosthesis has rarely been reported, and only a few cases have been documented. It is painful, disabling, costly, and may be associated with life-threatening sepsis even in a healthy individual. Removal of the implant is often required to eradicate the infection. Several early studies reported procedures to control the salmonella infection, but none described reconstruction of the destroyed hip joint. We present a case of salmonella sepsis 4 years after a total hip arthroplasty (THA). After prosthesis removal, radical debridement of the infected tissues, and administration of Imipenum (500 mg, 4 times daily), the systemic sepsis and hip infection were ameliorated. Four months later, a 2-stage revision THA was done for reconstruction of the hip joint. The clinical results 51 months following the THA procedure were satisfactory without an infectious reaction.

Primary cultures of human chondrocytes are susceptible to low inocula of Staphylococcus aureus infection and undergo apoptosis.

Hypocellularity after joint infection has been attributed to the cytotoxic effects of pus, which can cause necrosis of chondrocytes. In this study, primary cultures of human chondrocytes lost their viability and underwent necrosis rapidly with high inocula of Staphylococcus aureus infection. Chondrocytes were shown to undergo apoptosis with low inocula of Staphylococcus aureus or their culture ultrafiltrate. These findings further support the hypothesis that residual bacterial toxins or triggered apoptotic processes in chondrocytes participate in the pathogenesis of post-infectious arthropathy.

Vascularized island pedicle iliac bone grafting for avascular necrosis of the femoral head.

BACKGROUND: Nontraumatic avascular necrosis of the femoral head is a common disorder causing disability of the hip joint. The methods for optimally treating this disease in active young patients are still controversial. In this study we investigated the surgical outcome of vascularized pedicle iliac bone grafting for treating nontraumatic avascular necrosis of the femoral head. METHODS: Between 1994 and 1999, we treated 100 cases of avascular necrosis of the femoral head with vascularized pedicle iliac bone grafting. Thirty-nine hips in 33 patients were followed-up longer than 24 months. These patients included 30 men and 3 women, with an average age of 40 years. Steinberg's classification and Ohzono's types were used to categorize the diseased hips. The clinical results were evaluated using Charnley's modification of Merle d'Aubigne and Postel's numeric classification. RESULTS: Of the 33 patients, 82% were satisfied with their decision to have vascularized pedicle iliac bone grafting for avascular necrosis of the femoral head. No serious complications arose during this study. The average operation time for vascularized pedicle iliac bone grafting was 3.5 hours for one team. The rate of conversion to replacement arthroplasty was 10.3% (4 of 39 patients). CONCLUSION: Vascularized pedicle iliac bone grafting is a useful alternative treatment option for patients with avascular necrosis of the femoral head.

Biodegradable alginate antibiotic beads.

The authors investigated the poly-L-lysine-coated alginate beads as an antibiotic delivery system for the treatment of various surgical infections. The sodium alginate was mixed with vancomycin, coated with poly-L-lysine, and lyophilized to form five types of the biodegradable antibiotic beads. Type I, 2.5% alginate, nonpoly-L-lysine coated and nonlyophilized; Type II, 2.5% alginate, poly-L-lysine coated but nonlyophilized; Type III, 2.5% alginate, poly-L-lysine coated and lyophilized; Type IV, 5% alginate, poly-L-lysine coated and lyophilized; and Type V, 7.5% alginate, poly-L-lysine coated and lyophilized. Cytotoxicity of the alginate beads to fibroblasts and HeLa cells was evaluated by the MTT [3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H tetrazolium bromide] colorimetric assay. A study of in vitro elution of vancomycin of the alginate antibiotic beads was performed. The results suggested that the alginate antibiotic beads present no obvious toxic risk to their use as a drug delivery system. The concentration of vancomycin in these five types of beads was well above the breakpoint sensitivity concentration (the antibiotic concentration at the transition point between bacterial killing and resistance to the antibiotic) for 9,11,12, 14, and 17 days respectively. The release was most marked during the first 3 days. The duration of antibiotic release was prolonged by using techniques of poly-L-lysine coating, lyophilization, and by increasing the content of alginate. This study offers a biodegradable delivery system of antibiotics to treat various surgical infections.

Septic arthritis of the ankle joint.

BACKGROUND: Septic arthritis of the ankle joint is a rare but serious disease. Very few reports in the literature have mentioned the method of care and treatment results of septic ankle. This study was designed to retrospectively review the treatment results and to analyze the prognostic factors of septic arthritis of the ankle inpatients at our hospital. We also formulated a protocol for the management of septic arthritis of the ankle joint. METHODS: All records of those patients with a diagnosis of septic ankle from 1985 to 1997 were retrospectively reviewed. There were 29 patients that met the diagnostic criteria of septic arthritis of the ankle joint (21 male and 8 female patients; 6 children and 23 adults). The average follow-up time was 5.5 years (ranging from 1.5 to 13.7 years). The patients' ages, associated diseases, single or multiple joint(s) involved, timing of treatment, and the final results of these cases were assessed. The infecting organism and drug sensitivity were discussed to determine the proper antibiotics regimen. RESULTS: Staphylococcus aureus was the most common infecting microorganism in the septic ankles. Combined therapy with oxacillin and gentamicine was effective against 88.1% of the infecting microorganisms. The poor prognostic factors for septic ankle included a positive bacterial culture, involvement of multiple joints simultaneously, a delay in treatment, and an increased number of associated diseases. In addition, a high proportion of patients with septic ankle had gouty arthritis (43.5%). CONCLUSION: Early treatment (symptom duration of less than 5 days) significantly affected the final results. The early recognition and prompt treatment of this condition may reduce morbidity and mortality. Based on our results, oxacillin and gentamicine are recommended as the first-line antibiotics for the management of septic ankle.

Non-tuberculous cold abscess of the psoas muscle--an unusual manifestation of colocutaneous fistula.

We report here a case of colocutaneous fistula drained from the retroperitoneal space mimicking a cold abscess of the psoas muscle. A 60-year-old diabetic woman with a 6-year history of a chronic draining sinus over her right thigh had been treated intermittently with antibiotics. At presentation, she had no systemic toxic signs nor other constitutional symptoms. The patient was inadequately managed by curettage at first under the tentative diagnosis of tuberculous cold abscess. After the correct diagnosis of colocutaneous fistula, right nephrectomy and right hemicolectomy with ileotransverse colostomy were done. The patient was well 5 years later without recurrence. This is an atypical presentation of enterocutaneous fistula in an immunodeficient patient that should be emphasized to facilitate the correct diagnosis and early treatment.