Bovine bone grafting in occipito-cervical fusion for atlanto-axial instability in rheumatoid arthritis

Bovine bone chips (Surgibone) were used in occipito-cervical fusion in nine patients with atlanto-axial instability due to rheumatoid arthritis. The patients were examined with CT 12-15 months after surgery. Graft resorbtion was observed in one patient. The other 8 patients showed preserved grafts, in most cases the grafts appeared to be in contact with the underlying bone. One patient was revised, and at the grafted site a bony bridge was found. In conclusion, the use of bovine chips in posterior occipito-cervical fusion will not lead to predictable bone union. However, there seem to be exceptions to that rule.     

Hypothalamo-pituitary-thyroid system in patients with rheumatoid arthritis]

OBJECTIVE: To determine the effect on the uptake of breast screening of a personalized letter from the general practitioner recommending mammography, sent to coincide with an invitation from the NHS breast screening programme. DESIGN: Randomised control trial with stratification of prognostic variables. SETTING: A group practice in Hackney, east London. SUBJECTS: 473 women invited for breast screening by the City and East London Breast Screening Service. OUTCOME MEASURE: Attendance for mammography. RESULTS: All women in the randomised trial were followed up; 134 of 236 (57%) randomly allocated to receive the prompting letter attended for mammography compared with 120 of 234 (51%) controls This difference was not significant (chi 2 = 1.43, p = 0.23) CONCLUSION: Personal recommendation by a letter prompting attendance for mammography from the general practitioner known best to women due to be screened did not improve uptake of breast screening in this east London practice. Other strategies are needed to increase uptake of mammography in inner cities.     

Detection of joint pathology by magnetic resonance imaging in patients with early rheumatoid arthritis

Magnetic resonance imaging (MRI) permits the visualization of anatomical structures not appreciated by conventional radiographic imaging, and may assess inflammatory disease and its progression with greater sensitivity than conventional radiography. In this study of 30 patients with early rheumatoid arthritis (RA), which could be considered as a pilot study because of the relatively small number of patients, we compare MRI of the knee and the fifth metatarsophalangeal joint with clinical and radiographic findings. A parallel study of 10 healthy individuals served as a reference group. In all but one of the 30 patients, MRI revealed some kind of joint abnormality, whereas conventional radiography was normal in 14 patients. The present study thus suggests that MRI may detect inflammatory and/or destructive joint changes in patients with early RA, and that these changes may occur in the absence of clinical symptoms or signs and/or radiographic signs in the examined joint. If these data prove to be confirmed in further controlled studies, MRI may be of importance both for the assessment of prognosis and for the decision to treat in the early critical stages of RA.     

Adverse effects of low-dose methotrexate therapy in rheumatoid arthritis]

To analyze the possible adverse effects of low dose methotrexate (MTX) therapy, 276 patients with rheumatoid arthritis (RA) were examined retrospectively. One hundred and seven patients (39%) experienced 113 adverse events : 57 showed liver dysfunction, 24 gastrointestinal complaints, 13 cutaneous symptoms, 6 respiratory symptoms, and 6 malignancies. Interestingly, 3 patients developed a dry cough without infiltration nor interstitial shadow on chest X-ray. The cough was rapidly resolved by discontinuation of MTX, but it recurred in 1 patient when MTX was re-administered. This finding might suggest a close association between MTX administration and the occurrence of dry cough. Of the 6 patients with malignancies diagnosed during MTX therapy, 2 showed malignant lymphoma, 2 lung cancer, 1 breast cancer and 1 colon cancer. MTX might have an oncogenic potential in RA because the coincidence rate, especially with respect to lymphoma, was significantly higher than estimated in a normal population.     

Magnetic resonance imaging of the wrist in defining remission of rheumatoid arthritis

OBJECTIVE: To assess the efficacy of magnetic resonance imaging (MRI) in objectively defining a state of remission in rheumatoid arthritis (RA) after treatment. METHODS: Ten patients with RA involving the wrist were evaluated before treatment with methotrexate and hydroxychloroquine, and then mean 14 mo later with a followup evaluation. Clinical variables, laboratory measurements, and MRI using various techniques (T1 weighted image, T2 weighted image, fat suppression T2 weighted image, postcontrast T1 weighted image, postcontrast dynamic image, postcontrast 3 dimensional image) were observed. Remission was defined by ACR criteria. MRI changes were observed using 3 variables: extent of synovial proliferation; extent of bone marrow edema; and development of new erosion. In 6 of 10 patients, synovial signal intensity time curve changes at 30 s (E30 ratio) were determined for quantitative assessment of synovitis. RESULTS: Four patients achieved remission and 6 did not. All patients in remission showed decrease in extent of synovial proliferation and bone marrow edema with no newly developed erosion after treatment, compared to baseline. Five of 6 patients in nonremission showed newly developed erosions with variable changes in extent of synovial proliferation and bone marrow edema. E30 ratio was determined in 3 patients in the remission group and 3 in the nonremission group, with 48% reduction in the former compared to 9% reduction in the latter. CONCLUSION: MRI is feasible for objectively defining remission and assessing the therapeutic effect of antirheumatic drugs; utility of MRI measures in clinical remission criteria remains to be verified.     

Cartilage destruction in small joints by rheumatoid arthritis: assessment of fat-suppressed three-dimensional gradient-echo MR pulse sequences in vitro

In this study the small-intestine phenotype in rat colonic tumors was investigated in terms of sucrase and intestinal-type alkaline phosphatase (I-ALP) activity. F344 rats were given intraperitoneal injections of methylazoxymethanol acetate at a dose level of 25 mg/kg body weight once a week for 8 weeks and were killed 40 weeks after the first injection. Sucrase and I-ALP activities in proximal and distal colon adenocarcinomas were significantly higher than those in the normal colon epithelium. In the jejunum, by contrast, normal tissue had significantly higher levels than tumors. Immunohistochemical staining of I-ALP was also strong in striated cell borders of colon adenocarcinoma cells. These data suggest that, whereas absorptive cells of the small intestine lose their own traits with tumor development, colonocytes acquire phenotypic features of the small intestine. Intestinal enzymes associated with the striated-cell border, such as sucrase and I-ALP, may be useful markers for malignant phenotypic expression in colonocytes.     

Innovative treatment approaches for rheumatoid arthritis. New cyclo-oxygenase and cytokine inhibitors

A need remains for the development of more effective therapies for the treatment of rheumatoid arthritis (both NSAIDs and DMARDs). The NSAIDs remain the cornerstone of symptomatic therapy, but concern remains about their safety, potential for the delay in commencing definitive therapy and theoretical pro-inflammatory effects. Each of the NSAIDs reviewed here do provide an advantage over therapies previously available and should prove to be useful additions to the rheumatologists' therapeutic armament.     

New ultrasonic methods for measuring deformation and fracture related material states

The ability of ultrasonic measurements to detect and characterize discrete flaws in solids is well known. This paper discusses a series of new techniques which characterize distributed properties and their changes during mechanical deformation and fracture. Stress, texture, and porosity play important roles in the evolution of damage. Each influences the ultrasonic velocity, but difficulties in interpretation occur when more than one is unknown. However, the angular variation of the velocity can be used to differentiate those quantities. Examples are given of the use of velocity information to monitor these microstructural features during creep and large scale plastic deformation studies. It is then shown how ultrasonic scattering provides important information about the closure state near the tip of a fatigue crack and, thus, on the effective stress intensity factor and crack growth rate. A limitation in applying ultrasonics during mechanical testing is the size of the volume interrogated. Possible uses of high resolution acoustic microscopes to implement the above ideas on a smaller scale are indicated.     

Specificity of antiperinuclear factor for rheumatoid arthritis in rheumatoid factor-positive sera

Although antiperinuclear factor (APF) has the same specificity for rheumatoid arthritis (RA) as rheumatoid factor (RF), there is no evidence that this specificity is maintained in patients with positive RF-agglutination tests. Thus, we evaluated the specificity and usefulness of APF for RA diagnosis, regardless of RF titre. APF was tested (1:100 threshold) on 214 sera sent for RF evaluation over a 9-month period. These sera were previously determined to have latex or Rose-Waaler (RW) titres > or = 12 or 4 IU, respectively, but not necessarily above the threshold values of 100 and 32 IU. The APF test was performed blindly, and physicians were not advised of the results. In the patient population (119 RA and 95 non-RA) APF still demonstrated good specificity (0.82) for RA. As expected, APF proved useful for RA diagnosis in 28/33 (85%) RA cases with an RF level below 1:100 for latex and 1:32 for RW, thus reducing the number of 'seronegative' RA from 33/119 to 5/119. However, it also improved the serological positive predictive value for RA, even in cases when RW results were > or = 32 IU. Indeed, the positive predictive value for RA when both tests were positive was 0.94 (68/72), whereas concordant results (either positive or negative) for both APF and RW tests allowed correct classification (RA or non-RA) in 94% of cases.     

Calibration methods for measuring splenic sequestration by external scanning

Conventional methods for measuring splenic sequestration of labeled cells rely on stationary probe counting over the liver and spleen. A quantitative spleen-scanning method is proposed as a means of performing a more accurate diagnosis of the degree of splenic sequestration. Improved methods for calibrating a rectilinear scanner employing "constant resolutions" collimators, designed for the in vivo measurement, are reported, Clinical evaluation of this method was performed by scanning several patients scheduled for splenectomy. Good correlation between in vivo and in vitro measurements of splenic radioactivity for 29 patients was obtained. A least-squares fit to the data yielded a coefficient of determination r2=0.93.     

Gadolinium-DTPA enhanced magnetic resonance imaging of bone cysts in patients with rheumatoid arthritis

OBJECTIVES: To examine the contents of intraosseous cysts in patients with rheumatoid arthritis (RA) through the signal intensity characteristics on gadolinium-DTPA (Gd-DTPA) enhanced magnetic resonance imaging. METHODS: The hand or foot joints of nine patients with the cystic form of RA (where the initial radiological abnormality consisted of intraosseous cysts without erosions) were imaged before and after intravenous administration of Gd-DTPA. A 0.6 unit, T1 weighted spin echo and T2* weighted gradient echo were used to obtain images in at least two perpendicular planes. RESULTS: Most cysts showed a low signal intensity on the non-enhanced T1 weighted (spin echo) images and a high signal intensity on the T2* weighted (gradient echo) images, consistent with a fluid content. No cyst showed an enhancement of signal intensity on the T1 weighted images after intravenous administration of Gd-DTPA, whereas synovium hyperplasia at the site of bony erosions did show an increased signal intensity after Gd-DTPA. Magnetic resonance imaging detected more cysts (as small as 2 mm) than plain films, and the cysts were located truly intraosseously. In six patients no other joint abnormalities were identified by magnetic resonance imaging; the three other patients also showed, after Gd-DTPA administration, an enhanced synovium at the site of bony erosions. CONCLUSIONS: It is suggested that intraosseous bone cysts in patients with RA do not contain hyperaemic synovial proliferation. The bone cysts in patients with the cystic form of RA may be the only joint abnormality.     

Magnetic resonance imaging of bone destruction in rheumatoid arthritis: comparison with radiography

Bony changes in forty-four knees of patients with clinically established rheumatoid arthritis (RA) were examined using magnetic resonance imaging (MRI) and plain film radiography. In all cases MRI was clearly superior to radiographs, demonstrating 25 marginal erosions and 42 subchondral cysts, while the number seen on radiographs was 3 and 8, respectively. These results emphasize the problems in visualizing bone erosions in large joints using plain films. MRI is the method of choice for detecting early changes in RA, not only because of its high sensitivity, but also because of the ability of contrast-enhanced MRI to provide physiological characterization of these lesions.     

New imaging methods in diagnosis of lung cancer

The paper reviews new imaging methods allowing more precise diagnosing and staging of lung cancer. From among the methods currently used in clinical practice computed tomography and nuclear magnetic resonance were reviewed. Advantages and limitations of these techniques were presented. As for isotopic tests we reviewed single photon emission computed tomography and positron-emission tomography as well as novel endoscopic methods--lung imaging fluorescence bronchoscopy and video assisted thoracoscopy.     

Surgery for rupture of extensor tendons in rheumatoid arthritis

Forty-two patients underwent fifty-four operations for rupture of extensor tendons in rheumatoid disease. The results are analysed and factors affecting the results discussed.     

Analytical methods for measuring urea in pharmaceutical formulations

Two new methods are described for the routine determination of urea that utilize HPTLC-densitometry and colorimetry. The methods involve derivatization of urea with p-dimethylaminobenzaldehyde to a yellow-coloured compound. Validation of the methods was accomplished with respect to linearity, accuracy, reproducibility and limit of detection/quantification. Both methods were compared with an enzymatic method previously described in the literature and were found to be in close agreement. The proposed methods have the advantages of being simple, rapid and involve a single step sample preparation. Under experimental conditions HPTLC was the most sensitive method.     

Plain X-rays in rheumatoid arthritis: overview of scoring methods, their reliability and applicability

Radiographs are a suitable outcome measure in patients with rheumatoid arthritis. They reflect the history of the joint pathology and provide a permanent record necessary for serial evaluation of the disease. Great care should be taken to overcome technical problems with radiographs to ensure that good quality films are available to score. Many scoring methods have been described ranging from a global score for the whole patient to the more sophisticated methods of scoring erosions and joint space narrowing in a selected number of joints. These latter abnormalities give additive information and are the most important features in scoring radiographs in rheumatoid arthritis. An overview of the most important methods is given with an emphasis on four selected methods: the Larsen method, a modification of this by Rau and Herborn, the Sharp method and a modification of this by van der Heijde. All four methods produce sufficient intra- and inter-observer reliability. Although data are scarce, the Sharp method and its modifications seem the most sensitive methods for detecting changes over time. However, these are more time-consuming than the Larsen method or its modifications. Depending on the type of study a choice can be made between the two types of methods. For clinical trials where small differences are important, the (modified) Sharp method seems the most appropriate. In working with large data sets, time might be a more crucial factor and, therefore, the (modified) Larsen method could be chosen.     

Anti-ganglioside antibodies in patients with rheumatoid arthritis complicated by peripheral neuropathy

Gangliosides are a diverse class of glycolipids found in the plasma membrane of mammalian cells and are particularly abundant in cells of the nervous system. Serum antibodies to gangliosides have been detected in various neurological disorders with some evidence that they play a pathogenic role. In this study, we have investigated whether anti-ganglioside antibodies were elevated in a group of patients with rheumatoid arthritis (RA) who developed peripheral neuropathy (PN). An ELISA technique was used to test sera from 28 patients with RA and PN. 38 RA patients without PN and 20 normal controls for the presence of IgG and IgM anti-GM1 and sulphatide antibodies. The patients with RA and PN had higher pain scores (P < 0.005), more extra-articular features (P < 0.05), higher erosive scores (P < 0.0001), lower haemoglobin (P < 0.005), higher ESR (P < 0.001) and were more often on disease-modifying drugs (P < 0.05). Twelve RA patients with PN (43%), but only two RA controls (5%), had positive titres against one or more gangliosides (P < 0.001). The neurologic disability score (NDS) correlated with RA duration (P < 0.05), and with levels of IgM anti-GM1 (P < 0.001) and IgM anti-sulphatide (P < 0.05) antibodies. We conclude that PN is more common in patients with severe rheumatoid disease, and a significant proportion have elevated levels of anti-ganglioside antibodies.