Improved responsiveness to change in joint space width over 24-month follow-up: comparison of 3D JSW on weight-bearing CT vs 2D JSW on radiographs in the MOST study.

OBJECTIVE: Radiographic joint space width (JSW) has been a standard for measuring knee osteoarthritis (OA) structural change. Limitations in the responsiveness of this approach might be overcome by instead measuring 3D JSW on weight-bearing CT (WBCT). This study compared the responsiveness of 3D JSW measurements using WBCT with the responsiveness of radiographic 2D JSW. DESIGN: Standing, fixed-flexion knee radiographs (XR) and WBCT were acquired ancillary to the 144- and 168-month Multicenter Osteoarthritis Study visits. Tibiofemoral JSW was measured on both XR and WBCT. Responsiveness to change was defined by the standardized response mean (SRM) for change in JSW (1) at predetermined mediolateral locations (JSWx) on both modalities and (2) in the following subregions measured on WBCT images: central medial and lateral femur (CMF/CLF) and tibia (CMT/CLT), and anterior and posterior tibia (AMT/ALT, PMT/MLT). RESULTS: Baseline and 24-month follow-up JSWx measurements were completed for 265 participants (58.1% women). Responsiveness of 3D JSWx for medial tibiofemoral compartment on coronal WBCT (SRM range: -0.18, -0.24) exceeded that for 2D JSWx (-0.10, -0.16). Responsiveness of 3D JSW subregional mean (-0.06, -0.36) and maximal (-1.14, -1.75) CMF and CMT and maximal CLF/CLT 3D JSW changes were statistically significantly greater in comparison with respective medial and lateral 2D JSWx (P ≤ 0.002). CONCLUSIONS: Subregional 3D JSW on WBCT is substantially more responsive to 24-month changes in tibiofemoral joint structure compared to radiographic measurements. Use of subregional 3D JSW on WBCT could enable improved detection of OA structural progression over a 24-month duration in comparison with measurements made on XR.

Prevalence of intra-articular mineralization on knee computed tomography: the multicenter osteoarthritis study.

OBJECTIVE: The aim of this work was to report the prevalence of computed tomography (CT)-detected intra-articular mineralization. DESIGN: We included participants from the Multicenter Osteoarthritis (MOST) Study. At the 12th year visit of the MOST study, bilateral knee CTs were first obtained. All participants also had posteroanterior and lateral radiographs of bilateral knees and completed standard questionnaires. Knee radiographs were assessed for Kellgren & Lawrence grade (KLG) and radiographic evidence of intra-articular mineralization. CT images were scored using the Boston University Calcium Knee Score (BUCKS) for cartilage, menisci, ligaments, capsule, and vasculature. Prevalence of intra-articular mineralization was computed for the total sample, and stratified by age, sex, race, Body Mass Index (BMI), presence of frequent knee pain, and KLG. We also determined distribution of mineralization in the cartilage and meniscus, and co-localization. RESULTS: 4140 bilateral knees from 2070 participants were included (56.7% female, mean age 61.1 years, mean BMI: 28.8 kg/m2). On radiographs 240 knees (5.8%) had intraarticular mineralization, while CT-detected mineralization was present in 9.8% of knees. Prevalence of hyaline articular and meniscus mineralization increased with age and KL grade, and was similar by sex, BMI categories, and comparable in subjects with and without frequent knee pain. Mineralization tended to be ubiquitous in the joint, most commonly involving all three (medial/lateral tibiofemoral and patellofemoral) compartments (3.1%), while the patellofemoral compartment was the most involved compartment in isolation (1.4%). CONCLUSIONS: CT of the knee provides greater visualization of intra-articular mineralization than radiographs and allows better localization of the crystal deposition within the joint. Further studies should focus on the co-localization of intra-articular crystal deposition and corresponding magnetic resonance imaging (MRI)-features of knee osteoarthritis (OA).

Varus thrust during walking and the risk of incident and worsening medial tibiofemoral MRI lesions: the Multicenter Osteoarthritis Study.

OBJECTIVE: To determine the association of varus thrust during walking to incident and worsening medial tibiofemoral cartilage damage and bone marrow lesions (BMLs) over 2 years in older adults with or at risk for osteoarthritis (OA). METHOD: Subjects from the Multicenter Osteoarthritis Study (MOST) were studied. Varus thrust was visually assessed from high-speed videos of forward walking trials. Baseline and two-year MRIs were acquired from one knee per subject and read for cartilage loss and BMLs. Logistic regression with generalized estimating equations was used to estimate the odds of incident and worsening cartilage loss and BMLs, adjusting for age, sex, race, body mass index (BMI), and clinic site. The analysis was repeated stratified by varus, neutral, and valgus alignment. RESULTS: 1007 participants contributed one knee each. Varus thrust was observed in 29.9% of knees. Knees with thrust had 2.17 [95% CI: 1.51, 3.11] times the odds of incident medial BML, 2.51 [1.85, 3.40] times the odds of worsening medial BML, and 1.85 [1.35, 2.55] times the odds of worsening medial cartilage loss. When stratified by alignment, varus knees also had significantly increased odds of these outcomes. CONCLUSION: Varus thrust observed during walking is associated with increased odds of incident and worsening medial BMLs and worsening medial cartilage loss. Increased odds of these outcomes persist in varus-aligned knees.

Baseline trabecular bone and its relation to incident radiographic knee osteoarthritis and increase in joint space narrowing score: directional fractal signature analysis in the MOST study.

PURPOSE: To explore the association of baseline trabecular bone structure with incident tibiofemoral (TF) osteoarthritis (OA) and with increase in joint space narrowing (JSN) score. METHODS: The Multicenter Osteoarthritis Study (MOST) includes subjects with or at risk for knee OA. Knee radiographs were scored for Kellgren-Lawrence (KL) grade and JSN at baseline, 30, 60 and 84 months. Knees (KL ≤ 1) at baseline were assessed for incident OA (KL ≥ 2) and increases in JSN score. For each knee image at baseline, a variance orientation transform method (VOT) was applied to subchondral tibial bone regions of medial and lateral compartments. Seventeen fractal parameters were calculated per region. Associations of each parameter with OA incidence and with medial and lateral JSN increases were explored using logistic regression. Analyses were stratified by digitized film (DF) vs computer radiography (CR) and adjusted for confounders. RESULTS: Of 894 knees with CR and 1158 knees with DF, 195 (22%) and 303 (26%) developed incident OA. Higher medial bone roughness was associated with increased odds of OA incidence at 60 and 84 months and also, medial and lateral JSN increases (primarily vertical). Lower medial and lateral anisotropy was associated with increased odds of medial and lateral JSN increase. Compared to DF, CR had more associations and also, similar results at overlapping scales. CONCLUSION: Baseline trabecular bone texture was associated with incident radiographic OA and increase of JSN scores independently of risk factors for knee OA. Higher roughness and lower anisotropy were associated with increased odds for radiographic OA change.

Do persons with asymmetric hip pain or radiographic hip OA have worse pain and structure outcomes in the knee opposite the more affected hip? Data from the Osteoarthritis Initiative.

PURPOSE: To determine if asymmetry between hips in pain or radiographic osteoarthritis (RHOA) is associated with worse pain and joint space narrowing (JSN) at baseline and longitudinally in knees contralateral to more affected hips. METHODS: We studied 279 participants in the Osteoarthritis Initiative with baseline asymmetry between hips in pain and 483 with asymmetry in RHOA none of whom had a hip replacement for ≥4 years after baseline. RHOA assessed from pelvis radiographs was categorized as none, possible or definite and hip pain on most days of a month in the past year as present/absent. Knee pain (WOMAC scale) and JSN (fixed flexion radiographs) were categorized as none, mild and moderate-severe. We compared knees contralateral and ipsilateral to more affected hips on baseline knee pain and JSN using clustered multinomial regression and on change in knee pain and JSN over 4-5 years using generalized linear and logistic estimating equations. RESULTS: Knees contralateral to painful hips had less baseline pain ("moderate-severe" vs "none", relative risk ratio [RRR]: 0.39, 95% CI = 0.27-0.57), but greater baseline JSN ("moderate-severe" vs "none", RRR: 1.62, 95% CI = 1.09-2.38) and greater worsening of pain during follow-up (P = 0.001). Knees contralateral to hips with worse RHOA had nonsignificant trends for greater baseline JSN (P = 0.10) and JSN progression (P = 0.17). CONCLUSION: These findings provide limited support for the hypothesis that early asymmetry in hip pain and RHOA is associated with worse pain and structural outcomes in knees contralateral to the more affected hip.

High plasma levels of vitamin C and E are associated with incident radiographic knee osteoarthritis.

BACKGROUND: Previous studies suggest that the antioxidants vitamins C and E may protect against development of knee osteoarthritis (OA). We examined the association of circulating levels of vitamin C and E with incident whole knee radiographic OA (WKROA). METHODS: We performed a nested case-control study of incident WKROA in MOST, a cohort of 3,026 men and women aged 50-79 years with, or at high risk of, knee OA. Incident cases were knees without either tibiofemoral (TF) or patellofemoral (PF) OA at baseline that developed TF and/or PF OA by 30-month follow-up. Two control knees per case were selected from those eligible for WKROA that did not develop it. Vitamin C and E (alpha-tocopherol) assays were done on baseline supernatant plasma (PCA) and serum samples, respectively. We examined the association of gender-specific tertiles of vitamin C and E with incident WKROA using logistic regression with GEE, adjusting for age, gender, and obesity. RESULTS: Subjects without WKROA at baseline who were in the highest tertile of vitamin C had a higher incidence of WKROA [adjusted OR = 2.20 (95% CI: 1.12-4.33); P-value = 0.021], with similar results for the highest tertile of vitamin E [adjusted OR = 1.89 (1.02-3.50); P-value = 0.042], compared to those in the lowest tertiles. P-values for the trend of vitamin C and E tertiles and incident WKROA were 0.019 and 0.030, respectively. CONCLUSIONS: Higher levels of circulating vitamin C and E did not provide protection against incident radiographic knee OA, and may be associated with an increased risk of knee OA.

Pre-radiographic MRI findings are associated with onset of knee symptoms: the most study.

OBJECTIVE: Magnetic resonance imaging (MRI) has greater sensitivity to detect osteoarthritis (OA) damage than radiographs but it is uncertain which MRI findings in early OA are clinically important. We examined MRI abnormalities detected in knees without radiographic OA and their association with incident knee symptoms. METHOD: Participants from the Multicenter Osteoarthritis Study (MOST) without frequent knee symptoms (FKS) at baseline were eligible if they also lacked radiographic features of OA at baseline. At 15 months, knees that developed FKS were defined as cases while control knees were drawn from those that remained without FKS. Baseline MRIs were scored at each subregion for cartilage lesions (CARTs); osteophytes (OST); bone marrow lesions (BML) and cysts. We compared cases and controls using marginal logistic regression models, adjusting for age, gender, race, body mass index (BMI), previous injury and clinic site. RESULTS: 36 case knees and 128 control knees were analyzed. MRI damage was common in both cases and controls. The presence of a severe CART (P=0.03), BML (P=0.02) or OST (P=0.02) in the whole knee joint was more common in cases while subchondral cysts did not differ significantly between cases and controls (P>0.1). Case status at 15 months was predicted by baseline damage at only two locations; a BML in the lateral patella (P=0.047) and at the tibial subspinous subregions (P=0.01). CONCLUSION: In knees without significant symptoms or radiographic features of OA, MRI lesions of OA in only a few specific locations preceded onset of clinical symptoms and suggest that changes in bone play a role in the early development of knee pain. Confirmation of these findings in other prospective studies of knee OA is warranted.

A comparison of dedicated 1.0 T extremity MRI vs large-bore 1.5 T MRI for semiquantitative whole organ assessment of osteoarthritis: the MOST study.

OBJECTIVE: To date semiquantitative whole-organ scoring of knee osteoarthritis (OA) relies on 1.5 Tesla (T) Magnetic resonance imaging (MRI) systems. Less costly 1.0 T extremity systems have been introduced that offer superior patient comfort, but may have limitations concerning field-of-view and image quality. The aim of this study was to compare semi-quantitative (SQ) scoring on a 1.0 T system using 1.5 T MRI as the standard of reference. METHODS: The Multicenter Osteoarthritis Study (MOST) is a longitudinal study of individuals who have or are at high risk for knee OA. A sample of 53 knees was selected in which MRI was performed on a 1.0 T extremity system as well as on a 1.5 T scanner applying a comparable sequence protocol. MRIs were read according to the Whole Organ Magnetic Resonance Imaging Score (WORMS) score. Agreement was determined using weighted kappa statistics. Sensitivity, specificity and accuracy were assessed using the 1.5 T readings as the reference standard. In addition the number of non-readable features was assessed. RESULTS: Agreement (w-kappa) for seven main WORMS features (cartilage, bone marrow lesions (BMLs), osteophytes, meniscal damage and extrusion, synovitis, effusion) ranged between 0.54 (synovitis) and 0.75 (cartilage). Sensitivity ranged between 68.1% (meniscal damage) and 88.1% (effusion). Specificity ranged between 63.6% (effusion) and 96.4% (BMLs). Although the overall rate of non-readable features was very low, it was higher for the 1.0 T system (1.9% vs 0.2%). CONCLUSIONS: Semiquantitative whole organ scoring can be performed using a 1.0 T peripheral scanner with a moderate to high degree of agreement and accuracy compared to SQ assessment using a 1.5 T whole body scanner. Our results are comparable to the published inter- and intra observer exercises obtained from 1.5 T systems. Sensitivity to change of longitudinal scoring was not evaluated in this cross-sectional design and should be investigated in future validation studies.

[Isolation and study of antibiotic INA-1132 (chlorothricin), produced by actinomycete strain].

Taxonomic properties of strain INA-1132 producing antibiotic INA-1132 are described. The antibiotic showed activity against grampositive bacteria and fungi. The strain was classified as belonging to the genus Streptomyces and by its taxomic characteristics is most close to S. baarnensis. The experiments with the bacterial culture Halobacterium salinarum (previously H. halobium) revealed hypolipidemic activity of the antibiotic, i. e. its ability to inhibit biosynthesis of sterols. Conditions for the production of the antibiotic, methods of its isolation and purification, as well as the results of the chemical structure elucidation are described. By its physicochemical properties the antibiotic is identical to chlorothricin. The structure of antibiotic INA-1132 was ascertained by X-ray analysis. Conformation of the molecule of chlorothricin (antibiotic 1132) was determined for the first time.

The structure of nocamycin, a new antitumor antibiotic.

The structure of nocamycin, a new antitumor antibiotic, has been elucidated with the aid of mass- and PMR-spectroscopic investigation of the antibiotic and its various chemical transformation products. Nocamycin is structurally related to tirandamycins.

[The antineoplastic antibiotic polypeptide 308 produced by Actinomadura recticatena. Its isolation and physicochemical properties]. / Protivoopukholevyi antibiotik-polipeptid 308, produtsiruemyi Actinomadura recticatena. Vydelenie i fiziko-khimicheskie svoistva.

A antitumor antibiotic belonging to the group of polypeptide antibiotics containing chromophore was isolated from the culture of Actinomadura recticatena Terekhova, Preobrazhenskaya et Galatenko, 1984, strain 308. Biosynthesis, isolation, physicochemical and biological properties of the antibiotic are described. The results of elemental analysis, the melting point, optical properties, UV, IR and NMR spectra and the data on acid hydrolysis showed that antibiotic 308 was most closely related to antibiotic BBM-928 A.

[Early identification of streptothricin group antibiotics]. / Ranniaia identifikatsiia antibiotikov gruppy streptotritsinov.

Methodical approaches to detecting cultures producing streptothricins at the early stages of screening new antibiotics were developed. The approaches are based on chromatographic and electrophoretic mobility of streptothricins and the products of their hydrolysis in the extracts from agar cultures of actinomycetes. Application of the method for screening new antibiotics is illustrated with an example. Nine strains of actinomyces with broad antibacterial spectra isolated from soil samples were studied and 6 of them belonging to 4 species were shown to produce streptothricins in agar cultures. The new streptothricin-producing culture S. roseolilacinus was isolated.

[Actinomadura species as antibiotic producers]. / Vidy roda Actinomadura kak produtsenty antibiotikov.

Screening of antibiotic-producing cultures among Actinomadura showed that definite species mainly produced antibiotics of the same groups. Thus, carminomycins were produced by all the 4 studied strains of A. carminata, maduramycins were produced by 3 strains of A. rubra, prodigiozines were produced by 3 strains of A. madurae and luzopeptines were produced by 6 strains of A. recticatena. Supposedly, new antibiotics with original spectral characteristics were isolated from 2 strains of A. fulvescens. There was a clear-cut relation of the number of the active strains and their antibiotic productivity in definite media to their species. The liquid nutrient media, such as yeast-sucrose, soya-glucose and soya-glucose with cobalt chloride proved to be the most efficient in the primary screening of antibiotic-producing cultures.

[Screening of microbial secondary metabolites inhibiting cholesterol biosynthesis with the use of hepatoblastoma G2]. / Otbor mikrobnykh vtorichnykh matabolitov--ingibitorov biosinteza kholesterina s pomozh'iu kul'tury kletok gepatoblastomy G2.

The culture of hepatoblastoma G2 (Hep G2) cells is proposed as an effective model for screening of microbial metabolites--inhibitors of sterol biosynthesis. This model can be applied at early stages of screening procedures and is quite effective for testing of crude extracts of producers' culture broth. The test is based on measurement inhibition of the radiolabelled precursors incorporation in cholesterol and separate fractions of lipids by microbial metabolites in Hep G2 cells. That allows not only to reveal inhibitors of cholesterol biosynthesis, but also to evaluate mechanism of action, including ability to inhibit the synthesis of cholesterol ethers. The cholesterol biosynthesis inhibition was tested at 150 microbial cultures (actinomycetes and imperfect fungi), isolated from soil. The ability to inhibit 14C-acetate incorporation into cholesterol was found in 15-20% of microbial cultures possessing antifungal activity of extracts (culture broth and mycelium).

[Actinoplanes brasiliensis INA 3802--a producer of peptide antibiotics]. / Actinoplanes brasiliensis INA 3802--produtsent peptidnykh antibiotikov.

In the screening programme for new antibiotics an actinomycete culture designated as 3802 was isolated from a soil sample. The culture produced a complex of peptide antibiotics belonging to the group of lantibiotics. The antibiotic complex included gardimycin (actagardin) and new antibiotics of the same group. By the taxonomic properties strain 3802 was classified as Actinoplanes brasiliensis not previously known to produce gardimycin. Conditions of the antibiotic complex biosynthesis by strain 3802, the isolation methods and biological properties were studied.

[Production of griseoviridin and etamycin by the new culture, Streptomyces albolongus]. / Obrazovanie grizeoviridina i étamitsina novym produtsentom Streptomyces albolongus.

An actinomycete strain designated as 4297 was isolated from a soil sample collected near Moscow. The strain produced a complex of two antibiotics. One of them had a broad antibacterial spectrum and, in terms of its physicochemical properties and X-ray structural evidence, was identified with griseoviridin. The other was active against gram-positive bacteria and, by its chromatographic comparison with an authentic sample, mass spectroscopic determination of the molecular weight and UV spectra, was identified with etamycin. The strain 4297 differed from the described cultures producing griseoviridin and etamycin. By the taxonomic features it was classified as belonging to Streptomyces albolongus.

[The hypolipidemic action of antibiotic 86/88 (enniatin B) in a hepatoblastoma G2 cell culture]. / Gipolipidemicheskoe deistvie antibiotika 86/88 (énniatina B) v kul'ture kletok gepatoblastomy G2.

A cyclodepsipeptide antibiotic 86/88 (enniatin B) with strong hypolipidemic action was isolated from the culture liquid of the fungus INA F-86/88 identified as Fusarium lateritium Nees var. stilboides (Wr.) Bilai. In the Hep G2 cell culture the antibiotic suppressed 14C-acetate incorporation into cholesterol (IC50 1.75 microM), cholesterol ethers (IC50 1 microM), triglycerides (IC50 1.3 microM) and free fatty acids (IC50 2.2 microM). The most pronounced effect of the drugs, i.e. the suppression of the cholesterol ethers synthesis is likely due not only to the ACAT inhibition but also to the inhibition of the triglyceride synthesis and the diminishing of the free fatty acids pool in the cells.

[Specifics of sorption after purification of permeates produced by nanofiltration of washing water in pressurized modules]. / Osobennosti sorbtsionnoi doochistki permeatov, poluchennykh v rezul'tate nanofil'tratsii sanitarno-gigienicheskoi vody germozamknutogo ob"ekta.

Data on the quality of sorption afterpurification of permeates produced by nanofiltration of washing water in the ECOPSY-95 project are presented. Washing water contained essentially different detergents. Nanofiltration was performed with reeled composite membrane filters (OPMN-K). Nanofiltrated permeates were further treated with sorption techniques. The investigation confirmed the possibility get a filtrate complying with the washing water requirements. It was demonstrated that afterpurification of nanofiltered permeates by sorption improves the quality of regenerated water and also extends useful life of expandable sorption materials as compared to washing water that was not subjected to nanofiltration. Combination of nanofitration and sorption can be favorable to decrease the size of filter cartridges by 30-50%.

[Extraction of rifamycin B from native and aqueous solutions]. / Ekstraktsiia rifamitsina B iz nativnogo i vodnogo rastvorov

Optimal conditions for extraction of rifamycin B from aqueous solutions and fermentation broth filtrates at pH values within 2.0-7.0 were determined. When the antibiotic was extracted from the aqueous solutions, the highest yield was obtained at pH 2.0. When the antibiotic was extracted from the fermentation broth filtrates, it was found that chloroform was the most selective solvent with respect to rifamycin B, the chloroform selectivity being increased at pH 3.5-4.0. It was shown that rifamicin B passed from the buffer solutions with a concentration of 3-20 mg/ml to chloroform in amounts of 6-7 mg/ml and to ethylacetate and butanol in amounts of 20 mg/ml. Such conditions of chloroform and butanol (9 : 1) increased the rifamycin B contents in the extract up to 40 mg/ml.

[Physicochmemical characteristics of the new antineoplastic antibiotic, nocamycin]. / Fiziko-khimicheskaia kharakteristika novogo protivoopukholevogo antibiotika nokamitsina.

Nocamycin is produced by Nocardiopsis syringae. It is recovered from the culture fluid by extraction with chloroform. The molecular weight of the crystalline antibiotic is 503, its melting point is 147--149 degrees, [alpha]20 degrees D = --50 degrees (c. 0.21, chloroform), lambdamax235 and 348 nm(E1%sm= = 150 and 420), the summation formula is C26 H33NO9, the biological activity is 100000 Units/mg with respect to Bacillus mycoides. Nocamycin forms salts with alkalies soluble in water. On hydrolysis with an alkali it forms carbonic acid having no ester bond (IP spectrum) and methoxylic group present in the antibiotic molecule. Nocamycin is a new natural substance.