Pretreatment resistin levels are associated with erosive disease in early rheumatoid arthritis treated with disease-modifying anti-rheumatic drugs and infliximab.

OBJECTIVE: Resistin is an adipocytokine related to insulin resistance and inflammation. We investigated whether resistin is associated with disease activity and inflammation in disease-modifying anti-rheumatic drug (DMARD)-naïve rheumatoid arthritis (RA) patients, whether it has predictive value for radiological disease progression, and whether tumour necrosis factor-α (TNF-α) is involved in these effects. METHOD: Ninety-nine patients with early, DMARD-naïve RA participated in the NEO-RACo study. Patients were treated for the first 4 weeks with a combination of methotrexate, sulfasalazine, hydroxychloroquine, and prednisolone (FIN-RACo treatment). Thereafter, they were randomized to receive either infliximab or placebo added to the combination for 6 months. Patients were followed for 5 years. Disease activity was evaluated using the Disease Activity Score based on 28-joint count-erythrocyte sedimentation rate, radiographs were scored with the modified Sharp-van der Heijde method, and plasma resistin concentrations were measured by immunoassay. Human THP-1 macrophages were used in the in vitro studies. RESULTS: A high resistin level at baseline was associated with active inflammatory disease and predicted more rapid radiological progression during 5 year follow-up. Adding infliximab to the DMARD combination delayed radiological progression and overcame the poor predictive value of resistin. Resistin increased TNF-α production in human macrophages, indicating a possible connection between resistin and TNF-α. CONCLUSION: The results suggest that high resistin concentration may be a useful marker to distinguish patients with an increased risk of erosive disease in early active RA, and that adding TNF-α antagonist to the traditional DMARD combination may delay radiological progression of the disease in these patients. The study has been registered at https://www.clinicaltrials.gov(NCT00908089).

Disease activity in and quality of life of patients with psoriatic arthritis mutilans: the Nordic PAM Study.

OBJECTIVE: To describe the social status and health-related quality of life of patients with psoriatic arthritis mutilans (PAM) in the Nordic countries. METHOD: Patients with at least one mutilated joint confirmed by radiology were studied. Disease activity involving joints and skin, physician-assessed disease activity, and patient's education and work status were recorded. Data from the 36-item Short Form Health Survey, Health Assessment Questionnaire and Dermatology Life Quality Index questionnaire were gathered and correlated with disease duration, pain, and general well-being (visual analogue scale). The controls were 58 Swedish patients with long-standing psoriatic arthritis sine PAM. RESULTS: Sixty-seven patients were included. Patients with PAM had a protracted disease history (33 ± 14 years) and disease onset at a relatively early age (30 ± 12 years). Overall inflammatory activity at inclusion was mild to moderate. The mean number of mutilated joints was 8.2 and gross deformity was found in 16% of patients. Forty per cent were treated with biological and 32% with conventional synthetic disease-modifying anti-rheumatic drugs. Forty-two per cent had retired early or were on sick leave. Impaired functional capacity with little or no ability to perform self-care or everyday tasks was reported by 21% of the patients. Patients between 45 and 60 years of age reported the most impaired quality of life in comparison to the control group. CONCLUSION: PAM seriously affects social functioning. Whether early recognition of PAM and new forms of therapy can improve disease outcome and quality of life remains to be studied.

Effect of oral clodronate on structural damage and bone turnover in rheumatoid arthritis.

OBJECTIVES: To study the effect of oral clodronate on structural damage and bone metabolism in rheumatoid arthritis (RA). METHODS: In this 2-year proof-of-concept study, sixty patients with at least moderately active RA were randomised to receive anti-rheumatic therapy alone or together with oral clodronate 1600 mg daily. Radiographs of hands and feet and serum samples for bone biomarkers were studied at baseline and at 24 months. RESULTS: At 24 months, progression of radiographic joint damage was similar in the 2 groups. Clodronate suppressed carboxyterminal cross-linked peptide of type I collagen (p=0.03) and aminoterminal propeptide of type I procollagen (p=0.01). Eight patients (27%) withdrew from clodronate therapy due to adverse drug reactions. CONCLUSIONS: Oral clodronate did not retard the focal bone damage in RA despite its beneficial effect on overall bone metabolism, as judged by the decrease in the reference bone biomarkers.

Impact of early radiographic remission on the 15-year radiographic outcome in patients with rheumatoid arthritis.

OBJECTIVE: To investigate the 15-year radiographic outcome in patients with rheumatoid arthritis (RA) in relation to early radiographic remission. METHODS: A cohort of 87 patients with RA, treated with early-initiated disease-modifying anti-rheumatic drug (DMARD) therapy, was followed up prospectively for 15 years. Radiographs of hands and feet were taken at baseline and at 1, 2, 3, 5, 7, 10, and 15 years, and radiographs of large joints at 15 years. Radiographic outcome was assessed by the Larsen score (LS). Early radiographic remission was defined as a change of ≤ 1 Larsen unit in a year, during the first 2 years. RESULTS: A complete set of radiographs for evaluation was available from 69 patients. Outcome was evaluated in three groups: group A comprised 18 (26%) patients with sustained early radiographic remission (at both year 1 and year 2); group B comprised 20 (29%) patients with temporary early radiographic remission (at either year 1 or year 2); and group C comprised 31 (45%) patients with no early radiographic remission. Radiographic outcome was most favourable in patients with sustained early radiographic remission. The mean change in LS over 15 years was 11 [95% confidence interval (CI) 0-22] in group A, 30 (95% CI 12-51) in group B, and 62 (95% CI 45-81) in group C (p < 0.001). A similar relationship to large joint damage (Larsen large joint score) was seen. CONCLUSIONS: Compared with patients with progressive erosions, our results indicate that early radiographic remission relates to a better long-term radiographic outcome in RA regarding both small joint and large joint changes.

Anti-citrullinated peptide antibodies and the progression of radiographic joint erosions in patients with early rheumatoid arthritis treated with FIN-RACo combination and single disease-modifying antirheumatic drug strategies.

OBJECTIVES: To evaluate the impact of antibodies to cyclic citrullinated peptide (ACPAs) on radiographic progression in patients with early rheumatoid arthritis (RA) initially treated either with a combination of 3 disease-modifying antirheumatic drugs (DMARDs) or with a single DMARD. METHODS: This study included 129 patients with early active RA initially randomised to treatment either with a combination of methotrexate, sulfasalazine, hydroxychloroquine, and prednisolone (FIN-RACo) (n=69) or with a single DMARD (initially sulfalasalazine) with or without prednisolone (SINGLE) (n=60). After 2 years, the use of DMARDs and prednisolone became unrestricted. Radiographic progression in hands and feet was assessed at baseline and at 1, 2, 3, 4 and 5 years. ACPAs at baseline were determined with enzyme immunoassay. RESULTS: ACPAs were positive in 92 (71%) patients. ACPA-positive vs. negative patients were more frequently rheumatoid factor (RF) positive (83% vs. 22%, p<0.001) and had an erosive disease (54% vs. 22%, p<0.001) at baseline. The presence of ACPA was associated with radiographic progression in FIN-RACo group even when the impact of RF was controlled; the radiographic progression was remarkably slower in ACPA-negative than in ACPA-positive cases (RF adjusted change over time between groups p=0.034). In the SINGLE group, the radiographic changes progressed parallel in ACPA-negative and positive patients. CONCLUSIONS: Most ACPA-positive RA patients have joint erosions already at diagnosis. ACPA positivity in early RA was related to radiographic progression even in patients treated initially with the FIN-RACo regimen. The initial FIN-RACo therapy seems to slow down the progression of joint damage in ACPA-negative patients.

Prolonged systemic circulation of chimeric oncolytic adenovirus Ad5/3-Cox2L-D24 in patients with metastatic and refractory solid tumors.

Eighteen patients with refractory and progressive solid tumors were treated with a single round of triple modified oncolytic adenovirus (Ad5/3-Cox2L-D24). Ad5/3-Cox2L-D24 is the first non-Coxsackie-adenovirus receptor-binding oncolytic adenovirus used in humans. Grades 1-2 flu-like symptoms, fever, and fatigue were seen in most patients, whereas transaminitis or thrombocytopenia were seen in some. Non-hematological grades 3-5 side effects were seen in one patient with grade 3 ileus. Treatment resulted in high neutralizing antibody titers within 3 weeks. Virus appeared in serum 2-4 days after treatment in 83% of patients and persisted for up to 5 weeks. One out of five radiologically evaluable patients had partial response (PR), one had minor response (MR), and three had progressive disease (PD). Two patients scored as PD had a decrease in tumor density. Tumor reductions not measurable with Response Evaluation Criteria In Solid Tumors (RECIST) were seen in a further four patients. PR, MR, stable disease, and PD were seen in 12, 23.5, 35, and 29.5% of tumor markers analyzed, respectively (N=17). Ad5/3-Cox2L-D24 appears safe for treatment of cancer in humans and extended virus circulation results from a single treatment. Objective evidence of anti-tumor activity was seen in 11/18 (61%) of patients. Clinical trials are needed to extend these findings.

Can disease-modifying anti-rheumatic drugs be discontinued in long-standing rheumatoid arthritis? A 15-year follow-up.

OBJECTIVE: To investigate the 15-year outcome of patients with early rheumatoid arthritis (ERA) with respect to the continuity of treatment. METHODS: We conducted a 15-year follow-up study of 87 patients with ERA treated since diagnosis with disease-modifying anti-rheumatic drugs (DMARDs) according to the 'sawtooth' strategy. The patients were divided into groups according to the continuity of treatment: (A) 'continuous DMARDs', (B) 'discontinued and restarted DMARDs', and (C) 'permanently discontinued DMARDs'. The main outcome measurements included the Health Assessment Questionnaire (HAQ), the Larsen score, and clinical remission according to the American Rheumatism Association (ARA) criteria. RESULTS: Seventy (80%) patients participated in the 15-year follow-up. DMARDs were discontinued in 20 (29%) patients due either to remission or to a symptom-free period of the disease. The disease flared up in nine (45%) of these patients, in some patients several years after the discontinuation. At the 15-year follow-up, 59 (84%) patients were on DMARDs; only three (4%) were using biologicals. Functional capacity remained good in all groups (mean HAQ score 0.52). The mean Larsen score was higher (54) in group A than in groups B (25) and C (12) (p =0.001). The remission rate was 64% in group C and considerably lower in groups A (6%) and B (0%) (p<0.001). CONCLUSIONS: Our results indicate that most of the patients with long-standing RA require continuous DMARD treatment. If the treatment is discontinued, patients should be followed-up closely and DMARDs readministered without delay if the disease flares up.

Renal papillary necrosis in patients with IDDM.

Although diabetes mellitus is reported in 29% of patients with renal papillary necrosis (RPN), the frequency of RPN among patients with insulin-dependent diabetes mellitus (IDDM) has from autopsy studies been estimated to be only 4.4%. In vivo data on the prevalence of RPN in patients with IDDM have been lacking. We therefore studied the prevalence of RPN in 76 patients with long-standing IDDM and in 34 age-matched control subjects by intravenous urography. None of the control subjects showed radiographic signs of papillary necrosis. RPN was observed in 18 patients (23.7%); 15 were women (83.3%). Age and duration of diabetes was not different between patients with and without papillary necrosis, and there was no significant difference between the two groups regarding the prevalence of microangiopathic complications, i.e., proliferative retinopathy and diabetic nephropathy. Microscopic hematuria was three times more frequent in patients with than without RPN (44 vs. 16%; P less than .02). In addition, pyuria was reported in 40% of patients with papillary necrosis, and 61% of them gave a positive history of urinary tract infection compared to 16% (P less than 05) and 32% (P less than .02), respectively, in patients without papillary necrosis. It is concluded that RPN is a more frequent complication of long-standing IDDM than appreciated from autopsy studies, and being female and having a history of urinary tract infection are associated with an increased risk of RPN.

Screening for renovascular hypertension in a population with relatively low prevalence.

OBJECTIVE: To evaluate the accuracy and cost-efficacy of the diagnostic procedure and treatment for renovascular hypertension. SETTING AND PATIENTS: A total of 519 patients referred to the university clinic for hypertension were screened for renovascular hypertension with 405 captopril challenge tests (CCT) and 450 captopril renographies (CRG). INTERVENTIONS: Abdominal angiography was performed on 84 patients for positive screening. Fifteen patients underwent angiography for a sole suspicious clinical presentation. The angiography revealed 17 renal artery stenoses and five occlusions in 20 patients. Fifteen technically successful angioplasties and three nephrectomies were performed. RESULTS: In the patients who underwent angiography, CCT had a specificity of 39% and a sensitivity of 67% for renovascular hypertension. CRG had a sensitivity of 100% and a specificity of 68%. In the whole study population, the estimated specificity of CCT was 88% and that of CRG 95%. Invasive treatment reduced systolic/diastolic blood pressure from 157/99 to 140/87 mmHg and the number of antihypertensive drugs used from 2.6 to 1.4 in 16 patients (mean age 49 years). Angiotensin converting enzyme (ACE) inhibition was effective in four elderly patients. Cost-efficacy analysis Screening with CRG and invasive treatment cost US$15400 per successful invasive treatment Equally effective pharmacological treatment would have cost US$10400. Limiting the screening with CRG to the 173 patients with no obvious renal parenchymal disease and with hypertension at a younger age (< or =30 years) or unresponsive to two antihypertensive drugs (diastolic blood pressure > 90 mmHg) would have yielded a prevalence of 12% and missed only one elderly patient who responded to ACE inhibition. The limited screening, along with invasive treatment, would have cost US$7300 per patient CONCLUSIONS: CRG is superior to CCT for screening of renovascular hypertension. Screening with CRG is cost-effective when limited to patients with no obvious renal parenchymal disease and with hypertension that does not respond to two antihypertensive drugs or is detected in patients no older than 30 years.

The radiological assessment of rheumatoid arthritis.

Antirheumatic therapy has changed from a rather conservative approach towards more aggressive early intervention. Objective measures of the course and outcome of rheumatoid arthritis are essential to understand the disease process and evaluate the therapeutic response. Radiological evaluation fulfils many of the criteria of objectivity: the films provide a permanent record and can be evaluated serially and repeatedly; the changes do not fluctuate with disease activity; and good technique and correct timing can keep the radiation load to a very acceptable level. Consequently, therapies can be evaluated on the basis of their efficacy on radiological progression. In clinical practice, a visual qualitative assessment is usually sufficient, but for therapeutic trials or studies of disease progression in certain patient groups, quantitative methods are needed. A number of different evaluation systems have been introduced, but none of these have gained universal acceptance. No ideal evaluation method (which should be rapid, easy to use and have a good level of reproducibility) has yet been found. Here we make provisional recommendations on the conduct of future therapeutic trials to maximise the likelihood that they will give conclusive results using radiographic outcome assessments.

Renal mononuclear inflammatory cell populations in membranous glomerulonephritis: a fine-needle aspiration biopsy study.

Fine-needle aspiration biopsy (FNAB) technique was applied to the detection of alterations in renal inflammatory cell subsets in seven healthy control persons and 24 patients with membranous glomerulonephritis (MGN). Eighteen of the patients had nephrotic syndrome, and the rest had either persistent proteinuria or remission of the disease. Only one patient showed impaired renal function. Compared with the controls, FNAB revealed a significantly (p less than 0.01) increased number of mononuclear inflammatory cells (MIC, the sum in increment percentages of lymphocytes and monocytes) in MGN. This was mainly due to relative lymphocytosis; the number of monocytes was high particularly in patients with daily urine protein excretion in excess of 5 g. The duration of the disease did not clearly correlate with the degree of lympho- or monocytosis. In nine patients the results of the renal needle biopsy and FNAB could be compared. Biopsy revealed signs of MIC infiltration in 5/9 patients and FNAB in 7/9 patients. T-lymphocyte subsets in FNAB and peripheral blood were analyzed using monoclonal antibodies and indirect immunoperoxidase technique. The OKT4/OKT8 ratio in FNAB was 0.96 +/- 0.07 (s.e.m.) in patients and 1.49 +/- 0.12 in controls (p less than 0.01). In peripheral blood these ratios were 0.8 +/- 0.07 and 1.43 +/- 0.13 (p less than 0.001), respectively. The alterations were due to a decreased number of OKT4 positive lymphocytes. These studies suggest an associated interstitial accumulation of MIC and an imbalance between T helper/inducer and T suppressor/cytotoxic cells in MGN.

Interstitial cellular infiltration detected by fine-needle aspiration biopsy in nephritis.

Fine-needle aspiration biopsy (FNAB) was used to detect renal mononuclear interstitial inflammation in 56 patients with various types of nephritis (20 IgA nephropathy, 8 focal necrotizing glomerulonephritis, 7 interstitial nephritis, 6 non-classifiable chronic glomerulonephritis, 5 mesangial proliferative (non-IgA) chronic glomerulonephritis, 4 focal glomerulosclerosis, 6 normal histology, who were examined for microscopic hematuria, and 7 controls). Regular renal biopsies for histological and immunofluorescence studies were simultaneously obtained, and available for comparative analysis (not controls). Differential counts of mononuclear infiltration and subtyping of T-cell infiltration into T-helper (T-h) and T-suppressor-cytotoxic (T-s-c) cells, as detected by immunoperoxidase stains from FNAB, were correlated to clinical manifestations and renal function tests. Generally, our results indicated increased mononuclear cell infiltration (monocytes, lymphocytes, and/or activated lymphocytes) in FNAB of patients with IgA nephropathy, interstitial nephritis or focal necrotizing glomerulonephritis (especially monocytes in IgA nephropathy and interstitial nephritis, p less than 0.05 compared with controls, lymphocytes in focal necrotizing glomerulonephritis, and non-classifiable glomerulonephritis, p less than 0.02 and 0.05, respectively). The number of infiltrating activated lymphocytes was significantly increased in focal necrotizing glomerulonephritis, interstitial nephritis and focal glomerulosclerosis, p less than 0.05, less than 0.01 and less than 0.01, respectively. FNAB was at least as sensitive as histological examination for the quantification of interstitial cellular infiltration, and it allowed for cytological differential counts. Patients had decreased T-h and increased T-s-c cell counts, which were accentuated in FNAB compared with peripheral blood, although there were strong positive correlations between local and peripheral counts (p less than 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Steroid treatment and aseptic necrosis of the femoral head in renal transplant recipients.

The subject of our study was 546 renal transplant recipients with a graft survival for minimum 12 months. Of these, 29 renal recipients (5.3%) developed aseptic necrosis of the femoral head. The examination revealed that there were no significant differences between the renal recipients with hip necrosis and the control group in the total quantities of administered glucocorticosteroids, whereas there was a highly significant correlation between the two groups in the number of the intravenously administered methylprednisolone pulse doses.

Suitability of the scapular flap for reconstructions of the foot.

Eighteen patients with mainly a traumatic soft-tissue defect of the foot underwent reconstruction with a microvascular free scapular flap. Of the 17 successful transfers, 13 were to the weight-bearing parts of the foot. The stability and contour of the flaps were assessed after an average follow-up time of 3 years (range 1 to 5 years). The thicknesses of the scapular donor site and flap and the recipient site were measured by an ultrasound technique. The resistance of the flap to shear was measured with a dynamometer. The ultrasound measurements aided in refining our operative technique. In early cases, the flap thickness after transfer could be more than double what it was in the donor area. With proper tightening, the thickness could be reduced, with improvement in contour but no increase in soft-tissue stability or shear resistance of the flap. Without proper tightening, the scapular flap tended to be redundant when transferred to the foot. For good results, the patient should be lean, since the optimal thickness of the scapular donor site was less than 6 mm and the maximum thickness should not exceed 8 to 10 mm. The differences in shear resistance between the flaps were not associated with the soft-tissue stability of the reconstruction. The relative laxity of the flap on the plantar surface was found by several patients to be subjectively unpleasant. Although good contour could be achieved when covering the plantar heel, the tendency of the flap to develop abrasions and superficial breakdowns made it unsatisfactory for covering this area.(ABSTRACT TRUNCATED AT 250 WORDS)

Reposition of a displaced peritoneal catheter: the Helsinki whiplash method.

Dialysate outflow obstruction caused by displacement of the catheter tip is a relatively common complication of peritoneal dialysis, occurring in up to 20% of implanted catheters and often requiring surgical intervention. We describe a simple method used to reposition straight, Tenckhoff-type catheters. The procedure is performed under fluoroscopic control using a 2 mm thick catheter guide, bent fo form a slight curve. The catheter guide is introduced near the tip of the migrated catheter and then rotated in order to bring the catheter to the pelvis. Experiences over the five-year period 84-89 are summarized. In more than 60% of the patients, the first displacement occurred within one month of insertion of the catheter, and 70% of the catheters migrated to the right. The procedure was used in 21 patients to treat 50 displacements. In 86% of the cases the procedure was successful. 52% of the patients needed only one reposition while 48% experienced two or more displacements and subsequent repositions. Five patients eventually needed replacement of the catheter or were permanently switched to hemodialysis. The reposition procedure was practically free of complications.

Arterial stenosis in renal transplantation.

Stenosis of the renal artery of the transplant (RAT), is reported with a frequency of 5-10% (Nerstrøm, Ladefoged & Lund 1972, Nilsson, Henriksson & Thoren 1976, Beachley, Pierce, Boykin & Lee 1976). The stenosis is significant if it deteriorates the renal function or elevates the arterial blood pressure. The angiographic impression of a stenosis depends on the projection and it is difficult to correlate the radiological findings with the blood flow. Moreover both renal failure and hypertension might depend on other factors than stenosis of the RAT. The aim of this study was to establish how often a reconstruction of a RAT suspected of being stenotic would benefit the patient.