Clinical Effect of Doxycycline Combined with Compound Sulfamethoxazole and Rifampicin in the Treatment of Brucellosis Spondylitis.

OBJECTIVE: The purpose of this study was to determine the clinical value of triple antibiotic therapy consisting of doxycycline, compound sulfamethoxazole and rifampicin in the treatment of brucellosis spondylitis. METHODS: A retrospective analysis was performed on 100 patients with brucellosis spondylitis admitted to the First Affiliated Hospital of Hebei North University from March 2016 to June 2019. Patients were divided into the following two groups: the control group (n = 50) treated with dual antibiotic therapy (rifampicin + compound sulfamethoxazole), and the observation group (n = 50) treated with triple antibiotic therapy (rifampicin + doxycycline + compound sulfamethoxazole). The treatment effect, low back pain relief, levels of erythrocyte sedimentation rate (ESR), procalcitonin (PCT) and C-reactive protein (CRP), as well as the adverse reactions were compared between the two groups. RESULTS: The response rate of the observation group was significantly higher than that of the control group (P < 0.05). Before treatment, there was no significant difference in the low back pain assessed by the visual analogue scale (VAS), or levels of ESR, PCT and CRP between the two groups (P > 0.05). But after treatment, the VAS score and the levels of ESR, PCT and CRP in observation group were lower than those in the control group (P < 0.05). No significant difference was found in the incidence of adverse reactions (P > 0.05). CONCLUSION: The triple antibiotic therapy of doxycycline, compound sulfamethoxazole and rifampicin is effective in the treatment of brucellosis spondylitis. It can significantly alleviate patients' back pain and inflammation with a high safety profile, which is worthy of clinical application.

Increased and normalized uptake of 18F-FDG in a case of bone periprosthetic infection treated by antibiotics.

We report the case of a 69 years old man with left hip prosthesis, who presented clinical, biochemical and imaging signs of periprosthetic infection treated with linezolid, an antibacterial agent of the oxazolidinone class. Two weeks after this treatment, a fluorine-18-fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) scan showed increased uptake in the skeleton and also increased uptake in several focal areas in the spine and near the prosthesis and the surgical wound on the left gluteus medius. Bone marrow biopsy was negative; meanwhile the antibiotic therapy, after four weeks of treatment was stopped due to red blood cells and platelets toxicity. Six weeks later, the patient developed high fever again and in order to revaluate the periprosthetic inflammation, he was resubmitted to 18F-FDG PET/CT which showed normal 18F-FDG uptake in the whole skeleton, including the prosthesis and the subcutaneous wound. Some focal areas of increased uptake in the lumbar spine were still detected. In the next 4 weeks the patient was under a "watch and wait" follow-up in a steady state. IN CONCLUSION: In the case we report, since we found no otnt focal areas in the lumbar spine where due to age-related bone deformities including some Schmorl's nodes. The inflammation in the bone prosthesis and the subcutaneous wound responded almost totally to the antibiotic treatment we applied.

Whole-body Vibration at Thoracic Resonance Induces Sustained Pain and Widespread Cervical Neuroinflammation in the Rat.

BACKGROUND: Whole-body vibration (WBV) is associated with back and neck pain in military personnel and civilians. However, the role of vibration frequency and the physiological mechanisms involved in pain symptoms are unknown. QUESTIONS/PURPOSES: This study asked the following questions: (1) What is the resonance frequency of the rat spine for WBV along the spinal axis, and how does frequency of WBV alter the extent of spinal compression/extension? (2) Does a single WBV exposure at resonance induce pain that is sustained? (3) Does WBV at resonance alter the protein kinase C epsilon (PKCε) response in the dorsal root ganglia (DRG)? (4) Does WBV at resonance alter expression of calcitonin gene-related peptide (CGRP) in the spinal dorsal horn? (5) Does WBV at resonance alter the spinal neuroimmune responses that regulate pain? METHODS: Resonance of the rat (410 ± 34 g, n = 9) was measured by imposing WBV at frequencies from 3 to 15 Hz. Separate groups (317 ± 20 g, n = 10/treatment) underwent WBV at resonance (8 Hz) or at a nonresonant frequency (15 Hz). Behavioral sensitivity was assessed throughout to measure pain, and PKCε in the DRG was quantified as well as spinal CGRP, glial activation, and cytokine levels at Day 14. RESULTS: Accelerometer-based thoracic transmissibility peaks at 8 Hz (1.86 ± 0.19) and 9 Hz (1.95 ± 0.19, mean difference [MD] 0.290 ± 0.266, p < 0.03), whereas the video-based thoracic transmissibility peaks at 8 Hz (1.90 ± 0.27), 9 Hz (2.07 ± 0.20), and 10 Hz (1.80 ± 0.25, MD 0.359 ± 0.284, p < 0.01). WBV at 8 Hz produces more cervical extension (0.745 ± 0.582 mm, MD 0.242 ± 0.214, p < 0.03) and compression (0.870 ± 0.676 mm, MD 0.326 ± 0.261, p < 0.02) than 15 Hz (extension, 0.503 ± 0.279 mm; compression, 0.544 ± 0.400 mm). Pain is longer lasting (through Day 14) and more robust (p < 0.01) after WBV at the resonant frequency (8 Hz) compared with 15 Hz WBV. PKCε in the nociceptors of the DRG increases according to the severity of WBV with greatest increases after 8 Hz WBV (p < 0.03). However, spinal CGRP, cytokines, and glial activation are only evident after painful WBV at resonance. CONCLUSIONS: WBV at resonance produces long-lasting pain and widespread activation of a host of nociceptive and neuroimmune responses as compared with WBV at a nonresonance condition. Based on this work, future investigations into the temporal and regional neuroimmune response to resonant WBV in both genders would be useful. CLINICAL RELEVANCE: Although WBV is a major issue affecting the military population, there is little insight about its mechanisms of injury and pain. The neuroimmune responses produced by WBV are similar to other pain states, suggesting that pain from WBV may be mediated by similar mechanisms as other neuropathic pain conditions. This mechanistic insight suggests WBV-induced injury and pain may be tempered by antiinflammatory intervention.

MR spectroscopy findings in tuberculous spondylitis; comparison with Modic type-I end-plate changes and metastatic vertebral disease.

PURPOSE: To define single-voxel proton magnetic resonance spectroscopy (MRS) findings of vertebral tuberculous spondylitis (TBS), Modic type-I end-plate changes (MTEC) and metastatic vertebral disease (MVD). MATERIALS AND METHODS: Fifteen patients with TBS, 15 with MTEC and 15 with MVD were included. MRS from the diseased vertebral body as well as normal vertebral body was examined. Water and lipid peak were measured, water-to-lipid ratio (WLR) and for each patient lesion water index (LWI, the ratio of WLRs from diseased to normal vertebrae) were calculated. RESULTS: The mean WLR of normal and pathologic vertebra was 0.91 and 7.13 in TBS group, 0.84 and 3.49 in MTEC group and 0.65 and 3.17 in MVD group, respectively. The mean LWI was 10.68 in TBS, 6.04 in MTEC and 6.42 MVD groups. Statistical significance was not achieved between the WLR and LWI of the TBS, MTEC nor MVD group (p>0.05). CONCLUSION: The mean values of WLR and LWI in the TBS group are relatively higher than MTEC and MVD groups, with the difference being statistically insignificant.

Diagnosis and treatment of latent tuberculosis infection in arthritis patients treated with tumor necrosis factor antagonists in Korea.

Tumor necrosis factor (TNF) is essential for host defense against Mycobacterium tuberculosis, and the risk of reactivation of latent tuberculosis infection (LTBI) increases with anti-TNF therapy. This study estimated the prevalence of LTBI and evaluated the safety and completion rate of short-course therapy with isoniazid plus rifampin for 3 months to treat LTBI in a cohort of Korean arthritis patients before initiating anti-TNF therapy. We retrospectively studied the files of 112 consecutive patients to evaluate LTBI before starting anti-TNF drugs. Screening tests were performed, including a tuberculin skin test and chest radiography. LTBI treatment was indicated in 41 patients (37%). Of these, three patients refused the LTBI treatment. Of the 38 patients who underwent LTBI treatment, 36 (95%) took isoniazid plus rifampin for 3 months. Six patients (16%) showed transient elevations of liver enzymes during the LTBI treatment. Overall, 35 patients (92%) completed the LTBI treatment as planned. In conclusion, LTBI was diagnosed in one-third of Korean arthritis patients before initiating anti-TNF therapy. A high percentage of these patients completed 3 months of LTBI treatment with isoniazid plus rifampin without serious complications.

Diagnosis and Treatment of Latent Tuberculosis Infection in Arthritis Patients Treated with Tumor Necrosis Factor Antagonists in Korea

Tumor necrosis factor (TNF) is essential for host defense against Mycobacterium tuberculosis, and the risk of reactivation of latent tuberculosis infection (LTBI) increases with anti-TNF therapy. This study estimated the prevalence of LTBI and evaluated the safety and completion rate of short-course therapy with isoniazid plus rifampin for 3 months to treat LTBI in a cohort of Korean arthritis patients before initiating anti-TNF therapy. We retrospectively studied the files of 112 consecutive patients to evaluate LTBI before starting anti-TNF drugs. Screening tests were performed, including a tuberculin skin test and chest radiography. LTBI treatment was indicated in 41 patients (37%). Of these, three patients refused the LTBI treatment. Of the 38 patients who underwent LTBI treatment, 36 (95%) took isoniazid plus rifampin for 3 months. Six patients (16%) showed transient elevations of liver enzymes during the LTBI treatment. Overall, 35 patients (92%) completed the LTBI treatment as planned. In conclusion, LTBI was diagnosed in one-third of Korean arthritis patients before initiating anti-TNF therapy. A high percentage of these patients completed 3 months of LTBI treatment with isoniazid plus rifampin without serious complications.

The peptide repertoires of HLA-B27 subtypes differentially associated to spondyloarthropathy (B*2704 and B*2706) differ by specific changes at three anchor positions.

HLA-B*2704 is strongly associated with ankylosing spondylitis. B*2706, which differs from B*2704 by two amino acid changes, is not associated with this disease. A systematic comparison of the B*2704- and B*2706-bound peptide repertoires was carried out to elucidate their overlap and differential features and to correlate them with disease susceptibility. Both subtypes shared about 90% of their peptide repertoires, consisting of peptides with Arg(2) and C-terminal aliphatic or Phe residues. B*2706 polymorphism influenced specificity at three anchor positions: it favored basic residues at P3 and POmega-2 and impaired binding of Tyr and Arg at POmega. Thus, the main structural feature of peptides differentially bound to B*2704 was the presence of C-terminal Tyr or Arg, together with a strong preference for aliphatic/aromatic P3 residues. This is the only known feature of B*2704 and B*2706 that correlates to their differential association with spondyloarthropathy. The concomitant presence of basic P3 and POmega-2 residues was observed only among peptides differentially bound to B*2706, suggesting that it impairs binding to B*2704. Similarity between peptide overlap and the degree of cross-reaction with alloreactive T lymphocytes suggested that the majority of shared ligands maintain unaltered antigenic features in the context of both subtypes.

Subclinical gut inflammation in spondyloarthropathy patients is associated with upregulation of the E-cadherin/catenin complex.

OBJECTIVE: Previously an upregulation of E-cadherin and its associated molecules alpha-catenin, beta-catenin and plakoglobin has been demonstrated in clinically overt inflammatory bowel disease (IBD). The aim of this study was to investigate the expression of the E-cadherin/catenin complex in subclinically inflamed bowel mucosa from spondyloarthropathy (SpA) patients. METHODS: Ileal and colonic biopsy specimens from 19 SpA patients with subclinical inflammatory gut lesions and from seven controls were stained with monoclonal antibodies against E-cadherin, beta-catenin and plakoglobin and a polyclonal antibody against alpha-catenin. E-cadherin mRNA was detected using a riboprobe. Inflammation was histologically classified into acute, chronic active and chronic quiescent forms. RESULTS: In acute and chronic active bowel inflammation of SpA patients, upregulation of the E-cadherin/catenin glycoprotein complex could be observed. Chronic lesions in a quiescent state did not show such an upregulation. Furthermore, chronic inflammation was associated with an increase in E-cadherin mRNA. CONCLUSIONS: As some of the SpA patients with subclinical gut inflammation develop IBD, upregulation of the E-cadherin/catenin complex in inflamed bowel mucosa from SpA patients may point to early cellular changes in the development of IBD. However, at present it cannot be excluded that increased E-cadherin/catenin complex expression is a bystander phenomenon of active inflammation.

Misfolding of HLA-B27 as a result of its B pocket suggests a novel mechanism for its role in susceptibility to spondyloarthropathies.

The MHC class I protein HLA-B27 is strongly associated with susceptibility to spondyloarthropathies and can cause arthritis when expressed in rats and mice, implying a direct role in disease pathogenesis. A prominent hypothesis to explain this role suggests that the unique peptide binding specificity of HLA-B27 confers an ability to present arthritogenic peptides. The B pocket, a region of the peptide binding groove that is an important determinant of allele-specific peptide binding, is thought to be critical for arthritogenicity. However, this hypothesis remains unproven. We show that in addition to its role in peptide selection, the B pocket causes a portion of the pool of assembling HLA-B27 heavy chains in the endoplasmic reticulum to misfold, resulting in their degradation in the cytosol. The misfolding phenotype is corrected by replacing the HLA-B27 B pocket with one from HLA-A2. Our results suggest an alternative to the arthritogenic peptide hypothesis. Misfolding and its consequences, rather than allele-specific peptide presentation, may underlie the strong link between the HLA-B27 B pocket and susceptibility to spondyloarthropathies.

[Catecholamine metabolism in patients with neurological manifestations of spinal osteochondrosis]. / Obmin katekholaminiv u khvorykh z nevrolohichnymy proiavamy osteokhondrozu khrebta.

Catecholamines content was measured in blood plasma and urine in 104 patients presenting with different neurological syndromes of vertebral osteochondrosis. The results secured were compared to the values of vegetative cardiovascular tests in the same patients. Patients presenting with reflex vegetative muscular-and-tonic, reflex vegetovascular manifestations of vertebral osteochondrosis, and those patients presenting with radix symptomatology as well as those patients with reflex neurodystrophic manifestations (though less evident in the latter) were all diagnosed as having developed relatively high values for blood plasma content of norepinephrine at the expense of degeneration of peripheral vegetative nerve endings and reduction of the normal recapture of this mediator from the blood and its urine elimination. Diagnosing of high values for blood plasma and urine content of norepinephrine against the background of a striking inhibition of indices of vegetative cardiovascular tests in patients with vertebrogenic radix symptomatology suggest involvement into the bodily process of compensation and adaptation of suprasegmental vegetative nerve structures.

Interleukin-1beta in plasma and synovial fluid in relation to radiographic changes in arthritic temporomandibular joints.

The aim of this study was to investigate the level of the cytokine IL-1beta in plasma and temporomandibular joint (TMJ) synovial fluid of patients with arthropathies, and to study the relation between IL-1beta levels of synovial fluid and plasma as well as radiographic changes of the TMJ. 31 patients with general disease, 14 with rheumatoid arthritis (RA) and 17 with various arthritides were included in the study. Synovial fluid and blood samples were collected, and an individualized tomography of the TMJ was performed. Detectable levels of IL-1beta were found in 5 out of 39 synovial fluids and in 10 out of 27 plasma samples. The presence of IL-1beta in both plasma and synovial fluid was more frequent in RA patients than in the non-RA group. The extension of radiographic erosion was significantly greater in joints with IL-1beta than in those without. Both the extension of erosion and grade of radiographic changes of the TMJ were greater in patients with detectable IL-1beta level of plasma than in patients without. Our study indicates that presence of IL-1beta in plasma and synovial fluid is related to radiographic changes of the TMJ.

Biochemical markers of bone turnover in seronegative spondylarthropathy: relationship to disease activity.

To investigate bone turnover in patients with seronegative spondylarthropathy, a bone formation marker, type 1 procollagen carboxy-terminal propeptide (P1CP), and resorption markers, the pyridinium cross-links of collagen [urinary free (f) PYR and DPYR], were measured. The median f-PYR, f-DPYR and P1CP (+/-interquartile range) were 15.8 (6.00) nmol/mmol creatinine, 3.8 (2.2) nmol/mmol creatinine and 101.5 (38) micrograms/1, respectively. There was a positive correlation between resorption markers and acute-phase reactants such as C-reactive protein (r = 0.42 for PYR, r = 0.42 for DPYR, P < 0.05), and a negative correlation observed between P1CP and the erythrocyte sedimentation rate (r = -0.64, P < 0.05). In the subgroup of patients with an elevated CRP concentration, the concentration of PYR and DPYR was significantly increased (f-PYR 25.7 vs 15.8 and f-DPYR 6.6 vs 3.8, P < 0.01 for f-PYR, P < 0.05 for f-DPYR). This study suggests than an elevation in acute-phase response in patients with seronegative spondylarthropathy is associated with increased concentration of bone resorption markers with a tendency for reduction in bone formation markers. This may represent uncoupling of bone formation and resorption, leading to bone loss in such patients.

[Development and use of antitubercular biocompatible implants for the treatment of tuberculous spondylitis]. / Razrabotka i primenenie v lechenii tuberkulëznykh spondilitov biosovmestimykh implantatov, obladaiushchikh protivotuberkulëznoi aktivnostíu.

The paper deals with the experimental and clinical study of a new implantable therapeutical means based on biocompatible implants containing the antituberculous agent benemycin. The developed implantant having 4 coatings releases within 10 days as high as 37% of the applied drug benemycin. Then within further 30-70 days, release of the drug is 0.7% a day. The parallel bacteriological studies with the operative material placed in agar made 30-60 days after surgery have indicated that growth retardment in rabbits is 17-30 mm, which corresponds to the levels of rifandin (0.125-1.0 microgram/g tissue. The developed implantant has been used in 130 cases of the surgical treatment of tuberculous spondylitis in order to replace a defect of the body of a vertebra and to make a depot for the antituberculous drug just in the focus. Formation of the pulley at the site of intervention was noted in 57 (43.8%) cases within 5 months and in 62 (47.7%) cases within 10 months. The developed implantant has no toxicity and produces no allergic reactions. The position results of the treatment allows it to be recommended for use in clinical practice.

[Hormonal interrelationships in symptomatic epilepsy]. / Gormonal'nye vzaimootnosheniia pri simptomaticheskoi épilepsii.

The serum and cerebrospinal fluid (CSF) from patients with epilepsy resultant from cerebral leptomeningitis in the fit-free intervals were examined for some hypophyseal and adrenal hormones with reference to the disease course, severity and duration, frequency of the seizures. The levels of hydrocortisone, aldosterone and STH were found stable, while those of prolactin got elevated, especially in males. Hormonal shifts in the serum and CSF appeared significantly different. STH lowered, but prolactin went up only in CSF. The latter increase was related to the seizures frequency.

Synovial fluid concentration of five different cytokines in rheumatic diseases.

Interleukin-1 beta, interleukin-2, tumour necrosis factor alpha, and the interferons, alfa and gamma, were measured concurrently in synovial fluid samples from 68 patients with rheumatic diseases. Mean interleukin-1 beta concentrations (130.3 (SD 22) pg/ml) were higher in synovial fluids from patients with rheumatoid arthritis (RA) than in those from patients with osteoarthritis (27.8(4.5)pg/ml), while measurements in synovial fluids from patients with seronegative spondarthritis were intermediate (72.7 (32) pg/ml). Interleukin-2 and tumour necrosis factor alpha concentrations were lower in the inflammatory arthropathies (RA: 4.5 (0.6) U/ml, 0.39 (0.04) ng/ml; seronegative spondarthritis: 3.1 (0.3) U/ml, 0.33 (0.03) ng/ml respectively) than those in patients with osteoarthritis (5.2 (0.6) U/ml; 0.05 (0.04) ng/ml). Interleukin-2 and tumour necrosis factor alpha concentrations correlated in all groups (r = 0.7), as did the interferons alfa and gamma (r = 0.7). There was no relation between interleukin-1 beta and either interleukin-2 or tumour necrosis factor alpha, or between the interferons and any other cytokine. Several distinct cytokine patterns were noted. Synovial fluids from two non-arthritic subjects were also examined: interleukin-1 beta concentrations were low, but concentrations of the other cytokines were higher than those seen in most arthritic fluids.

[Biochemical criteria of the inflammatory process in spinal osteomyelitis]. / Biokhimicheskie kriterii vospalitel'nogo protsessa pri osteomielite pozvonochnika.

Patterns of collagen metabolism were studied in 36 patients with hematogenic vertebral column osteomyelitis simultaneously with evaluation of C-reactive protein, haptoglobin and ceruloplasmin in blood and consideration of the clinico-morphological steps of the disease. Hyperhydroxyprolineuria proved to be a more informative evidence for inflammation in vertebral column as compared with the proteins of acute phase of inflammation importance of hydroxyproline measurement in biological fluids for evaluation of the osteomyelitis development was elevated as the inflammation activity decreased (which was estimated by content of the acute phase proteins).

Progressive ankylosis (ank/ank) in mice: an animal model of spondyloarthropathy. II. Light and electron microscopic findings.

Murine progressive ankylosis was studied by light and electron microscopy (EM). By light microscopy, the earliest synovial lesion was inflammatory followed by synovial proliferation and cartilage erosions. Later changes included progressive joint ankylosis by fibrosis and ossification of articular and periarticular tissues and new bone proliferation. By EM, synovial cell proliferation and hypertrophy with collagen deposition was seen before the appearance of intracellular and extracellular hydroxyapatite crystals. These pathologic changes are the same as those found in the human spondyloarthropathies. Our EM findings demonstrate that hydroxyapatite crystals appear in the joints of ank/ank mice after the initial inflammatory phase.

Universal spondylodiscitis in a patient with erosive peripheral arthritis and apatite crystal deposition.

A patient with erosive peripheral arthritis in whom vasculitis and monoclonal IgG kappa paraprotein were associated with sacroiliitis and widespread destruction of intervertebral discs is reported. Crystals resembling apatite were identified in intervertebral disc material, and we postulate that the discitis was accelerated by apatite deposition. Our case illustrates a unique example of axial involvement in rapidly progressive joint disease.