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1.
Osteoarthritis Cartilage ; 31(1): 11-17, 2023 01.
Article in English | MEDLINE | ID: mdl-36191832

ABSTRACT

Assessment and treatment of Bone Marrow Lesions (BMLs) could ultimately make step changes to the lives of people with osteoarthritis (OA). We here review the imaging and pathological characteristics of OA-BMLs, their differential diagnosis and measurement, and cross-sectional and longitudinal associations with pain and OA structural progression. We discuss how biomechanical and cellular factors may contribute to BML pathogenesis, and how pharmacological and non-pharmacological interventions that target BMLs might reduce pain and OA structural progression. We critically appraise semiquantitative and quantitative methods for assessing BMLs, and their potential utilities for identifying people at risk of symptomatic and structural OA progression, and evaluating treatment responses. New interventions that target OA-BMLs should both confirm their importance, and reduce the unacceptable burden of OA.


Subject(s)
Bone Diseases , Cartilage Diseases , Osteoarthritis, Knee , Humans , Bone Marrow/pathology , Osteoarthritis, Knee/pathology , Cross-Sectional Studies , Magnetic Resonance Imaging/methods , Cartilage Diseases/pathology , Pain/pathology , Bone Diseases/pathology , Knee Joint/pathology
2.
Osteoarthritis Cartilage ; 30(5): 746-755, 2022 05.
Article in English | MEDLINE | ID: mdl-35124198

ABSTRACT

OBJECTIVES: Bone marrow lesions (BMLs) are associated with pain in osteoarthritis (OA), but histological scores for OA focus on cartilage pathology. We developed a new scoring system, the Osteoarthritis Bone Score (OABS), to characterise OA-related BMLs. METHODS: BML/non-BML tissues identified by Magnetic Resonance Imaging (MRI) in 10 knee OA subjects were harvested at total knee replacement (TKR). Osteochondral tissue from a further 140 TKR and 23 post-mortem (PM) cases was assessed. Histological features distinguishing MRI-defined BML/non-BML tissues on qualitative analysis were classified as present (0) or absent (1), summated for the OABS, validated by Rasch analysis and sensitivity to distinguish between sample groups. Immunohistochemistry for PGP9.5 assessed innervation. RESULTS: Subchondral characteristics associated with BML tissues were cysts, fibrosis, hypervascularity, cartilage islands, trabecular thickening, loss of tidemark integrity and inflammatory cell infiltration. PGP9.5 immunoreactive perivascular nerves were associated with BMLs. OABS performed well as a measurement tool, displayed good reliability (Cronbach alpha = 0.68), had a 2-factor structure (trabecular/non-trabecular), with moderate correlation between the two factors (r = 0.56, 95% CI 0.46, 0.65). OABS scores were higher in TKR than PM cases with chondropathy, median difference 1.5 (95% CI -2, 0). OABS and Mankin scores similarly distinguished TKR from non-OA controls, but only OABS was higher in BML than non-BML tissues, median difference -4 (95% CI -5 to -2). CONCLUSIONS: OABS identifies and validly quantifies histopathological changes associated with OA BMLs. Histopathology underlying BMLs may represent 2 inter-related pathological processes affecting trabecular/non-trabecular structures. Increased vascularity/perivascular innervation in BMLs might contribute to pain.


Subject(s)
Bone Diseases , Cartilage Diseases , Osteoarthritis, Knee , Bone Diseases/pathology , Bone Marrow/diagnostic imaging , Bone Marrow/pathology , Bone and Bones/pathology , Cartilage Diseases/pathology , Humans , Knee Joint/diagnostic imaging , Knee Joint/pathology , Magnetic Resonance Imaging/methods , Osteoarthritis, Knee/diagnostic imaging , Osteoarthritis, Knee/pathology , Osteoarthritis, Knee/surgery , Pain/pathology , Reproducibility of Results
3.
Osteoarthritis Cartilage ; 29(3): 365-371, 2021 03.
Article in English | MEDLINE | ID: mdl-33422704

ABSTRACT

OBJECTIVE: To investigate which cardiometabolic factors underlie clustering of osteoarthritis (OA) with cardiovascular disease, and the extent to which these mediate an effect of education. DESIGN: Genome-wide association study (GWAS) of OA was performed in UK Biobank (60,800 cases and 328,251 controls) to obtain genetic association estimates for OA risk. Genetic instruments and association estimates for body mass index (BMI), low-density lipoprotein cholesterol (LDL-C), systolic blood pressure (SBP), smoking and education were obtained from existing GWAS summary data (sample sizes 188,577-866,834 individuals). Two-sample Mendelian randomization (MR) analyses were performed to investigate the effects of exposure traits on OA risk. MR mediation analyses were undertaken to investigate whether the cardiometabolic traits mediate any effect of education on OA risk. RESULTS: MR analyses identified protective effects of higher genetically predicted education (main MR analysis odds ratio (OR) per standard deviation increase 0.59, 95% confidence interval (CI) 0.54-0.64) and LDL-C levels (OR 0.94, 95%CI 0.91-0.98) on OA risk, and unfavourable effects of higher genetically predicted BMI (OR 1.82, 95%CI 1.73-1.92) and smoking (OR 2.23, 95%CI 1.85-2.68). There was no strong evidence of an effect of genetically predicted SBP on OA risk (OR 0.98, 95% CI 0.90-1.06). The proportion of the effect of genetically predicted education mediated through genetically predicted BMI and smoking was 35% (95%CI 13-57%). CONCLUSIONS: These findings highlight education, obesity and smoking as common mechanisms underlying OA and cardiovascular disease. These risk factors represent clinical and public health targets for reducing multi-morbidity related to the burden these common conditions.


Subject(s)
Blood Pressure/genetics , Cardiometabolic Risk Factors , Cholesterol, LDL/genetics , Educational Status , Obesity/epidemiology , Osteoarthritis/epidemiology , Smoking/epidemiology , Aged , Body Mass Index , Female , Genome-Wide Association Study , Humans , Male , Mediation Analysis , Mendelian Randomization Analysis , Middle Aged , Obesity/genetics , Odds Ratio , Osteoarthritis/genetics , Smoking/genetics
5.
QJM ; 99(2): 69-79, 2006 Feb.
Article in English | MEDLINE | ID: mdl-16434469

ABSTRACT

Patients with multi-system rheumatic conditions may have disease affecting the central and peripheral nervous systems. Early assessment is often helpful in averting the development of serious complications, which in some conditions can be prevented by the prompt institution of treatment. We review the spectrum of neurological disease in patients with a rheumatological diagnosis. The wide variety of associated neurological complications is discussed in the context of specific rheumatic conditions, varying from spinal cord involvement in rheumatoid arthritis, to neuropsychiatric involvement in systemic lupus erythematosus and neurological sequelae in vasculitic disorders. We discuss diagnostic criteria and recommended management options (where available), and describe the role of new tools such as functional brain imaging in the diagnosis and monitoring of disease. We also discuss the potential for development of neurological complications from the use of anti-rheumatic drugs.


Subject(s)
Connective Tissue Diseases , Musculoskeletal Diseases , Sarcoidosis , Vasculitis , Antirheumatic Agents/adverse effects , Connective Tissue Diseases/complications , Connective Tissue Diseases/diagnosis , Connective Tissue Diseases/drug therapy , Humans , Immunosuppressive Agents/administration & dosage , Musculoskeletal Diseases/complications , Musculoskeletal Diseases/diagnosis , Musculoskeletal Diseases/drug therapy , Sarcoidosis/complications , Sarcoidosis/diagnosis , Sarcoidosis/drug therapy , Vasculitis/complications , Vasculitis/diagnosis , Vasculitis/drug therapy
7.
Ann Rheum Dis ; 61(1): 10-2, 2002 Jan.
Article in English | MEDLINE | ID: mdl-11779750

ABSTRACT

BACKGROUND: Gut involvement in inflammatory myositis is rare but causes significant morbidity and mortality. CASE REPORT: A case of eosinophilic gastroenteritis and polymyositis occurring in the same patient is described. The interface of visceral and striated muscle involvement is discussed. The pathophysiology of eosinophilic gastroenteritis and the spectrum of gastrointestinal involvement in inflammatory myositis are also discussed. RESULTS: Both gastrointestinal and skeletal muscle symptoms improved with immunosuppression, suggesting a possible common underlying mechanism.


Subject(s)
Eosinophilia/complications , Gastroenteritis/complications , Polymyositis/complications , Alpha-Globulins/therapeutic use , Anti-Inflammatory Agents/therapeutic use , Eosinophilia/drug therapy , Female , Gastroenteritis/drug therapy , Humans , Immunosuppressive Agents/therapeutic use , Methotrexate/therapeutic use , Middle Aged , Polymyositis/drug therapy , Prednisolone/therapeutic use , Treatment Outcome
11.
Int J Clin Pract ; 54(4): 269-71, 2000 May.
Article in English | MEDLINE | ID: mdl-10912321

ABSTRACT

We report a case of Cushing's syndrome due to primary pigmented nodular adrenal dysplasia (PPNAD) and discuss the diagnostic process and management of this rare case. The diagnosis of PPNAD is discussed in the context of other causes of Cushing's syndrome. Eighty-five per cent of cases of Cushing's syndrome are due to a pituitary corticotrophic tumour (Cushing's disease). Rarer causes include cortisol secreting adrenal adenoma and ectopic ACTH secretion. In the routine investigation of Cushing's disease it is not unusual to find bilateral adrenal nodules on the CT scan. We present a case of Cushing's syndrome in which this radiographic finding was present and yet the biochemical diagnosis was one of ACTH independent disease. Histology revealed PPNAD.


Subject(s)
Adrenal Gland Diseases/complications , Cushing Syndrome/etiology , Hyperplasia/complications , Adrenal Gland Diseases/diagnostic imaging , Adrenalectomy , Adult , Female , Humans , Hyperplasia/diagnostic imaging , Radiography, Abdominal , Tomography, X-Ray Computed
12.
J Accid Emerg Med ; 16(4): 296-8, 1999 Jul.
Article in English | MEDLINE | ID: mdl-10417945

ABSTRACT

A 25 year old man presented with anuria and bilateral leg pain two days after an alcoholic binge. He subsequently developed rhabdomyolysis causing acute renal failure, with compartment syndrome of both lower legs. This required urgent dialysis and fasciotomy respectively within six hours of admission. He remained dialysis dependent for three weeks and only after four months was he able to weight bear on both legs. Alcohol is a leading cause of rhabdomyolysis. Early recognition and prompt treatment is essential to prevent serious complications.


Subject(s)
Acute Kidney Injury/etiology , Alcoholic Intoxication/complications , Compartment Syndromes/etiology , Rhabdomyolysis/etiology , Acute Kidney Injury/diagnosis , Acute Kidney Injury/therapy , Adult , Compartment Syndromes/rehabilitation , Compartment Syndromes/surgery , Emergency Service, Hospital , Follow-Up Studies , Humans , Male , Orthopedic Procedures/methods , Renal Dialysis , Rhabdomyolysis/diagnosis , Rhabdomyolysis/therapy , Treatment Outcome
13.
J Clin Microbiol ; 30(11): 2938-40, 1992 Nov.
Article in English | MEDLINE | ID: mdl-1452664

ABSTRACT

Chlamydia trachomatis diagnosis in our laboratory consisted of dual inoculation of shell vials and detection of inclusions by using fluorescein-conjugated monoclonal antiserum; the second culture vial was conventionally used for blind passage when the first vial was negative. We compared the increase in positivity using blind passage with that of a strategy utilizing observation of two stained monolayers (dual observation) without blind passage, in an effort to reduce the reporting time and labor associated with the conventional approach. A total of 4,329 specimens were obtained from an obstetrics and gynecology (OB-GYN) clinic (2,563 specimens) and the sexually transmitted disease clinic (1,766 specimens). These specimens were used to compare the two strategies. Blind passage of 1,269 initially culture-negative specimens from the OB-GYN clinic resulted in an additional 6 positive chlamydial diagnoses. In comparison, a similar number of specimens (1,294) from the OB-GYN clinic collected subsequently to the first group were tested by dual observation. There were five additional positive findings. A similar evaluation of specimens from the sexually transmitted disease clinic was performed. Blind passage of 313 initially culture-negative specimens yielded 3 additional positive diagnoses, whereas dual observation of 1,435 similar specimens resulted in 9 positive diagnoses. On the basis of analysis of 4,332 specimens, sensitivity of dual observation is comparable to that of blind passage; labor, cost, and reporting time of dual observation are reduced in comparison to those of blind passage.


Subject(s)
Bacteriological Techniques , Chlamydia Infections/diagnosis , Chlamydia trachomatis/isolation & purification , Sexually Transmitted Diseases, Bacterial/diagnosis , Bacteriological Techniques/economics , Bacteriological Techniques/statistics & numerical data , Chlamydia Infections/epidemiology , Costs and Cost Analysis , Evaluation Studies as Topic , Female , Humans , Male , Sensitivity and Specificity , Sexually Transmitted Diseases, Bacterial/epidemiology , United States/epidemiology
14.
J Clin Microbiol ; 29(4): 842-5, 1991 Apr.
Article in English | MEDLINE | ID: mdl-1653788

ABSTRACT

We evaluated a 12-min, direct, monoclonal antibody-based enzyme immunoassay (EIA) (SureCell; Kodak, Rochester, N.Y.) which aids in the detection of herpes simplex virus infection; the assay system is also approved for culture confirmation. The test was evaluated from direct clinical samples and compared with conventional culture methodology by using a single swab. A total of 265 specimens from 180 female cervical-urogenital sites, 62 male urogenital sites, 4 rectal sites, 3 skin sites, 6 oral sites, and 10 colposcopy sites were collected on Dacron or cotton swabs and placed in viral transport medium (VTM). Within 6 h of receipt, 0.2 ml of the vortexed VTM was inoculated into each of two replicate cell cultures. Cell monolayers were observed daily for ten days, and cytopathic effect was confirmed by using an indirect immunoperoxidase reagent. The procedure for the SureCell assay conformed to the manufacturer's recommendations. When conventional culture was compared with EIA results, the overall sensitivity, specificity, positive predictive value, negative predictive value, and agreement were 64.4, 98.9, 96.7, 84.4, and 87.2%, respectively. Variables affecting the EIA sensitivity are the stage of the lesion and conventional culture methodologies. A review of culture results for 32 EIA false-negative tests indicated that 15 were detected after 48 h of incubation. Cytopathic effect observed at 48-, 72-, and 96-h cutoffs altered the sensitivity for the EIA. To ensure detection of SureCell herpes simplex virus-negative specimens, it is recommended that an unused aliquot of VTM be tested in cell culture.


Subject(s)
Antigens, Viral/analysis , Genitalia/microbiology , Herpes Simplex/diagnosis , Immunoenzyme Techniques , Simplexvirus/immunology , Cytopathogenic Effect, Viral , Evaluation Studies as Topic , Female , Herpes Simplex/pathology , Humans , Male , Sensitivity and Specificity , Simplexvirus/growth & development
15.
J Clin Microbiol ; 28(9): 2139-41, 1990 Sep.
Article in English | MEDLINE | ID: mdl-2121795

ABSTRACT

Diagnosis of brucellosis requires prompt detection and identification of the coccobacillus for appropriate patient management, as the organism is associated with a potentially severe outcome. In a recent experience, an 18-year-old migrant farm worker presented at a local hospital with nonspecific symptoms. A significant Brucella titer of 2,560 was followed by the recovery of a gram-negative coccobacillus, subsequently identified as Brucella abortus, from subcultured 5-day-old BACTEC NR730 negative blood cultures. The organism proved to be susceptible to a variety of antimicrobial agents and resistant to nitrofurantoin. The patient was administered antimicrobial therapy for Brucella spp. consisting of tetracycline and streptomycin for 21 days. During the course of therapy the patient experienced defervescence and was discharged with the recommendation for periodic follow-up examinations. Seeded culture studies of this isolate with fresh human blood and target inocula of 5 and 500 CFU/ml indicated that the larger (500-CFU/ml) inoculum produced positive instrument detection within 2 days, whereas the smaller (5-CFU/ml) inoculum required 5.5 to 7.5 days for detection, depending on the medium used. These findings underscore the potential for Brucella bacteremia to escape instrument detection given a low bacterial inoculum.


Subject(s)
Brucella abortus/isolation & purification , Brucellosis/diagnosis , Sepsis/diagnosis , Adolescent , Bacteriological Techniques , Blood/microbiology , Brucella abortus/growth & development , Culture Media , Humans , Male , Time Factors
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