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D Kuntz

Publications and source records attributed to D Kuntz.

At least 19 recordsLinked to original sources

Evaluation of Roche Diagnostics ONLINE DAT II, a new generation of assays for the detection of drugs of abuse.

A new generation of ONLINE assays has been developed that offers improved performance and enhanced ease of use. This family of assays is being applied to both the COBAS INTEGRA and Roche/Hitachi line of analyzers. The four ONLINE DAT II assays that were evaluated included cocaine (benzoylecgonine) (BE), methadone (MDN), opiates (OP), and tetrahydrocannabinol (THC). The BE assay has a dual cutoff (150/300 ng/mL) with a dynamic range from 0 to 5000 ng/mL. The MDN assay has a cutoff of 300 ng/mL with a dynamic range from 0 to 2000 ng/mL. The opiates assay has a 300 ng/mL cutoff with a 0 to 2000 ng/mL range and a 2000 ng/mL cutoff with a 0 to 8000 ng/mL range. The THC assay has 20, 50, and 100 ng/mL cutoffs with 0 to 100, 0 to 300, and 0 to 300 ng/mL dynamic ranges, respectively. The ranges of the intra-assay precision (coefficients of variation for n = 20) run in the semiquantitative mode are 2.3-7.5% for BE, 2.0-3.8% for MDN, 1.9-4.2% for OP, and 3.9-5.2% for THC. The intra-assay qualitative precision for all of the assays as calculated from absorbance values is generally higher than that of the intra-assay semiquantitative precision at the cutoff. The qualitative precision ranges between 0.4% and 3.1%. The standard curve stability defined for the COBAS INTEGRA systems for these reagents ranges from 35 to 68 days. The clinical sensitivity and specificity were compared to the OnLine generation I and CEDIA immunoassays, as well as gas chromatography-mass spectrometry (GC-MS). The results indicate that for each assay, the sensitivity and specificity were the same or greater when compared to the other two immunoassay technologies. The results of each assay also correlated very well (> 99%) when compared with GC-MS.

Automation↗

Prophylactic use of alfacalcidol in corticosteroid-induced osteoporosis.

One hundred and forty-five patients suffering from diseases requiring long-term treatment with high doses of corticosteroids (30 mg/day or greater of prednisolone) were recruited to the study. Patients had to be steroid naive on entry to the study (not more than 15 days of treatment with a corticosteroid within the previous 24 months). Patients were randomized to receive either 1 microgram/day alfacalcidol or placebo capsules for 12 months. Bone mineral density (BMD) of the lumbar spine was assessed by dual-photon absorptiometry on entry and after 3, 6 and 12 months' treatment. Safety was monitored by the recording of all adverse events reported by patients and the regular screening of blood samples for hematology and serum biochemistry. Of the 145 patients, 74 were randomized to alfacalcidol and 71 to placebo. The treatment groups were well matched at baseline with no significant differences in demographic, clinical or biochemical parameters. The mean equivalent dose of prednisolone at baseline was 46.6 mg/day and 46.3 mg/day for the alfacalcidol and placebo group respectively. From the 145 patients randomized to treatment, 71 (38 who received alfacalcidol and 33 who received placebo) provided BMD data both at baseline and at 3, 6 and 12 months. The percentage change in BMD after 6 months' treatment was -2.11% in the alfacalcidol group and -4.00% in the placebo group (p = 0.39). After 12 months the percentage change in BMD was +0.39% (CI: -4.28 to 4.81) in the alfacalcidol group and -5.67% (CI: -8.13 to -3.21) in the placebo group, this difference (6.06%, CI: 0.88 to 11.24) being statistically significant (p = 0.02). An intention to treat analysis also showed a significant difference between the two treatment groups in alfacalcidol's favor (3.81%, p = 0.01; CI: 0.92 to 6.70). There was no significant difference between the two treatment groups in the corticosteroid dose at any time point during the study. Serum calcium was measured throughout and there were no significant differences between the two treatment groups at any visit. This study suggests that alfacalcidol can prevent corticosteroid-induced bone loss from the lumbar spine. Long-term use of alfacalcidol was not associated with any significant adverse effects in this diverse group of patients.

Adjuvants, Immunologic↗

Spinal tuberculosis in adults. A study of 103 cases in a developed country, 1980-1994.

Spinal tuberculosis (TB) accounts for about 2% of all cases of TB. New methods of diagnosis such as magnetic resonance imaging (MRI) or percutaneous needle biopsy have emerged. Two distinct patterns of spinal TB can be identified, the classic form, called spondylodiscitis (SPD) in this article, and an increasingly common atypical form characterized by spondylitis without disk involvement (SPwD). We conducted a retrospective study of patients with spinal TB managed in the area of Paris, France, between 1980 and 1994 with the goal of defining the characteristics of spinal TB and comparing SPD to SPwD. The 103 consecutive patients included in our study had TB confirmed by bacteriologic and/or histologic studies of specimens from spinal or paraspinal lesions (93 patients) or from extraspinal skeletal lesions (10 patients). Sixty-eight percent of patients were foreign-born subjects from developing countries. None of our patients was HIV-positive. SPD accounted for 48% of cases and SPwD for 52%. Patients with SPwD were younger and more likely to be foreign-born and to have multiple skeletal TB lesions. Neurologic manifestations were observed in 50% of patients, with no differences between the SPD and SPwD groups. Of the 44 patients investigated by MRI, 6 had normal plain radiographs; MRI was consistently positive and demonstrated epidural involvement in 77% of cases. Bacteriologic and histologic yields were similar for surgical biopsy (n = 16) and for percutaneous needle aspiration and/or biopsy (n = 77). Cultures for Mycobacterium tuberculosis were positive in 83% of patients, and no strains were resistant to rifampin. Median duration of antituberculous chemotherapy was 14 months. Surgical treatment was performed in 24% of patients. There were 2 TB-related deaths. Our data suggest that SPwD may now be the most common pattern of spinal TB in foreign-born subjects in industrialized countries. The reasons for this remain to be elucidated.

Adolescent↗

Nonsurgical treatment of osteoarticular tuberculosis. A retrospective study in 143 adults.

OBJECTIVE AND METHODS: Data are sparse on nonsurgical treatments currently used for osteoarticular tuberculosis in industrialized countries. We conducted a multicenter retrospective study in the Paris urban area, France, in 206 cases of osteoarticular tuberculosis documented by examination of a local specimen. This article reports our findings in the 143 patients who were followed up at least until treatment completion. RESULTS: Mean follow-up after treatment completion was 16 months. Seventy-five (52%) patients had spondylitis and 68 (48%) did not. The number of antituberculous agents used during the initial treatment phase was four in 65% of cases and three in 35%. In the spondylitis subgroup, mean (+/- SD) antibiotic therapy duration was 14.7 +/- 3.4 months, and 25% of patients required surgery; 3% of patients died, 1% suffered a relapse, and 96% achieved a full recovery with no relapse. In the nonspondylitis subgroup, mean antibiotic therapy duration was 13 +/- 3 months and 29% of patients required surgery. The only HIV-positive patient had osteitis of the calcaneus with a relapse that led to discovery of secondary rifampin resistance. CONCLUSION: Based on our findings and on data from the literature, we believe that 12 months is a reasonable duration for antituberculous therapy in osteoarticular tuberculosis, including tuberculous spondylitis.

Adolescent↗

Osteonecrosis-like syndrome of the medial tibial plateau can be due to a stress fracture. MR findings in 13 patients.

OBJECTIVE: To demonstrate the contribution of magnetic resonance imaging to the elucidation of mechanisms involved in "osteonecrosis-like syndrome of the medial tibial plateau". PATIENTS AND METHODS: A magnetic resonance study with sagittal and coronal sections was done in 13 patients (age range, 57-95 years) two weeks to four months into a painful syndrome meeting the definition of "osteonecrosis-like syndrome of the medial tibial plateau". Gadolinium injection was used in nine patients. Clinical symptoms resolved within a few weeks in all 13 cases. RESULTS: T1-weighted images without gadolinium showed diffuse low signal from the epiphysis (n = 12) containing an area of even lower signal seen either as a crescent-shaped subchondral image (n = 3/12) or as a linear image (n = 9/12). On postgadolinium images, the low signal was abolished except for a line of low signal parallel to the subchondral bone. T2-weighted images demonstrated diffuse high signal from the medial tibial plateau with persistence of the line of low signal (n = 8/12). CONCLUSION: Magnetic resonance imaging allows to analyze the anatomic lesion responsible for "osteonecrosis-like syndrome of the medial tibial plateau". Our magnetic resonance findings were similar to those seen in stress fractures at other sites.

Aged↗

New susceptibility locus for rheumatoid arthritis suggested by a genome-wide linkage study.

Rheumatoid arthritis (RA), the most common autoimmune disease, is associated in families with other autoimmune diseases, including insulin-dependent diabetes mellitus (IDDM). Its genetic component has been suggested by familial aggregation (lambdas = 5), twin studies, and segregation analysis. HLA, which is the only susceptibility locus known, has been estimated to account for one-third of this component. The aim of this paper was to identify new RA loci. A genome scan was performed with 114 European Caucasian RA sib pairs from 97 nuclear families. Linkage was significant only for HLA (P < 2.5.10(-5)) and nominal for 19 markers in 14 other regions (P < 0.05). Four of the loci implicated in IDDM potentially overlap with these regions: the putative IDDM6, IDDM9, IDDM13, and DXS998 loci. The first two of these candidate regions, defined in the RA genome scan by the markers D18S68-D18S61-D18S469 (18q22-23) and D3S1267 (3q13), respectively, were studied in 194 additional RA sib pairs from 164 nuclear families. Support for linkage to chromosome 3 only was extended significantly (P = 0.002). The analysis of all 261 families provided a linkage evidence of P = 0. 001 and suggested an interaction between this putative RA locus and HLA. This locus could account for 16% of the genetic component of RA. Candidate genes include those coding for CD80 and CD86, molecules involved in antigen-specific T cell recognition. In conclusion, this first genome scan in RA Caucasian families revealed 14 candidate regions, one of which was supported further by the study of a second set of families.

Arthritis, Rheumatoid↗

Cytokine release from marrow mononuclear cells is negatively correlated to cortical elasticity in non-osteoporotic postmenopausal women.

Activation of bone remodeling is likely to be under the control of mechanical factors acting, in part, through soluble local factors. We therefore investigated a relationship between cytokine production by marrow cells and bone elasticity. We studied 36 non-osteoporotic postmenopausal women undergoing hip arthroplasty for hip arthrosis (mean age: 68 +/- 8 years; lumbar BMD Z-score: +0.54 +/- 0.33 SD). Adherent marrow mononuclear cells were cultured for 48 hours with autologous plasma, and supernatants were harvested for PGE2, IL-1, TNF-alpha, and IL-6 measurements. Femoral neck cortical bones were removed during surgery for cortical histomorphometric evaluation and determination of elasticity indices (C33) using ultrasonic transmission method. In this nonosteoporotic population, femoral neck longitudinal elasticity indices were inversely correlated to both cortical thickness (r = -0.58, P < 0.01) and cortical porosity (r = -0.33, P < 0.01). The longitudinal elasticity indices were also negatively correlated to basal IL-1 and TNF-alpha release by adherent mononuclear marrow cells (r = -0.59, P < 0.01; r = -0.60, P < 0.01, respectively). However, no relationship was found between the three cytokines tested and either cortical thickness or porosity. These data show a link between cortical biomechanical properties and local factors involved in bone remodeling. We suggest that increased bone elasticity decreases transmission of strain, which in turn decreases cytokine release from marrow cells. However, whether cytokines influence bone elasticity or vice versa remains to be demonstrated.

Aged↗

Bone mass in middle-aged osteoporotic men and their relatives: familial effect.

Severe idiopathic osteoporosis in middle-aged men is still poorly understood. The aim of this study was to assess the contribution of genetic factors in these patients. We studied 38 men (mean age +/- SD, 50 +/- 11 years) presenting with vertebral or peripheral bone fractures due to primary osteoporosis and 73 of their relatives divided into four subgroups: 19 brothers, 22 sisters, 13 sons, and 19 daughters. The control group comprised 199 age-matched subjects. In all subjects, we measured bone mineral density (BMD) and calculated the Z score at the lumbar spine (LS) and femoral neck (FN) based on the fitted BMD value in the controls. LS BMD values were lower in each of the four subgroups compared with the age-matched controls. The mean Z score for the overall group of 73 relatives was decreased compared with the age-matched controls (-1. 28 +/- 1.48 at the LS and -1.03 +/- 1.19 at the FN) and was not influenced by gender or by whether the relatives were siblings or children. An LS Z score < -1) was found in 54.8% of the relatives of osteoporotic patients versus 17.4% of the control subjects (risk ratio, 3.2). Alcohol and tobacco abuse are well-known risk factors for osteoporosis in men. Among the 38 osteoporotic patients, 7 were heavy smokers (>20 pack-years), 8 were both heavy smokers and drinkers (>80 g/day for at least 10 years and gammaGT > 40 UI/l), and 23 had neither of these risk factors. BMD, Z score, and anthropometric data were the same in patients with and without risk factors. Decreases in LS and FN Z scores were similar in relatives of patients with and without risk factors. In conclusion, low BMD is observed in relatives of osteoporotic men with or without risk factors for osteoporosis, indicating that familial factors contribute to primary osteoporosis in middle-aged men.

Absorptiometry, Photon↗

[Epidemiological aspects of osteoarticular tuberculosis in adults. Retrospective study of 206 cases diagnosed in the Paris area from 1980 to 1994].

OBJECTIVES: The aim of this study was to determine the epidemiologic features of bone and joint tuberculosis in the Paris area from 1980 to 1994. METHODS: This retrospective study included 206 cases of confirmed bone and joint tuberculosis (in situ specimen) diagnosed from 1980 to 1994 in 7 hospital units (mainly rheumatology clinics) in Paris and suburban areas. RESULTS: The number of cases increased by a mean 12 per year from 1980 to 1989 then by 17 cases per year from 1990 to 1994. In both 1993 and 1994 there were 21 cases per year. The percentage of immigrant patients was 53% from 1980 to 1989 then reached 74% for 1990-1994, predominantly in subjects from black Africa. Only one patient in the series had human immunodeficiency virus (HIV) infection. A favoring factor was found in 23% of the immigrant and in 45% of the native French patients. Mean age was 37 years in immigrants and 58 years in French patients. Compared with French patients, immigrants had a higher rate of multifocal bone and joint tuberculosis, peripheral osteitis and spondylitus. CONCLUSION: Our findings suggest that the incidence of bone and joint tuberculosis has increased in Paris in 1993 and 1994. Two populations are especially susceptible: the elderly and/or immunodepressed French population and immigrants coming from endemic zones. The role or HIV infection was minimal in this predominantly rheumatology series.

Adult↗

Association of rheumatoid arthritis with an amino acid allelic variation of the T cell receptor.

OBJECTIVE: To investigate allelic variations of T cell receptor residues for a contribution to rheumatoid arthritis (RA) susceptibility. METHODS: We conducted an RA case-control study involving 1,579 northwest Europeans: 766 patients with erosive and rheumatoid factor-positive disease and 813 control subjects. Productive changes of segments TCRAV6S1, TCRAV7S1, TCRAV8S1, TCRAV10S2, and TCRBV6S1, TCRBV6S7 were investigated by single-strand conformation polymorphisms. The TCRAV8S1 association was confirmed by restriction fragment length polymorphism. RESULTS: In the systematic study (77 patients and 119 controls), an increase in 1 TCRAV8S1 genotype was found in the RA patients (P = 0.0004). This finding was replicated in 2 further populations, one from France (212 patients and 254 controls) and the other from Britain (477 patients and 440 controls), with a similar odds ratio (OR), which allowed pooling of the data and confirmation of the association (OR 1.3 [95% confidence interval 1.1-1.7], P = 0.008). CONCLUSION: These findings show evidence that TCRA is an RA susceptibility locus.

Alleles↗

Effects of cyclical etidronate therapy on bone loss in early postmenopausal women who are not undergoing hormonal replacement therapy.

This study was carried out to investigate the effectiveness and tolerability of cyclical etidronate therapy in the prevention of bone loss occurring in early postmenopausal women who are not undergoing hormone replacement therapy (HRT). A total of 109 Caucasian women aged 45-60 years were treated with etidronate 400 mg/day or placebo for 14 days followed by calcium supplementation 500 mg/day for 77 days. Ninety-one women completed the 2 years of the study. After 2 years, the estimated difference between the two groups as regards lumbar spine bone mineral density (BMD) was 2.53% (SEM 1.07%; p = 0.01); BMD of the hip and wrist were not significantly different between treatment groups. A clear reduction in bone turnover was obtained as evidenced by a significant decrease in serum alkaline phosphatase level and in urinary N-telopeptide/ creatinine ratio in the etidronate group; the difference between the two groups was -12% +/- 3.2% for serum alkaline phosphatase level (p = 0.019) and -22.9% +/- 13.7% for the urinary N-telopeptide/creatinine ratio (p = 0.047). There was no statistically significant difference between the two groups in terms of the serum osteocalcin levels and urinary hydroxyproline/ creatinine and calcium/creatinine ratios. Etidronate was generally well tolerated and its adverse event profile was similar to that of placebo. The results of this study indicate that cyclic etidronate therapy can prevent trabecular bone loss, with no deleterious effect on cortical bone, in the first 5 years of menopause and that it has a very high safety margin.

Alkaline Phosphatase↗

[Analgesic effect and clinical tolerability of the combination of paracetamol 500 mg and caffeine 50 mg versus paracetamol 400 mg and dextropropoxyphene 30 mg in back pain].

OBJECTIVES: A double-blind randomized multicentric study was performed to test the hypothesis that the analgesic effect of paracetamol-cafeine is equivalent to that of paracetamol-dextropropoxyphen in patients suffering from pain due to osteoarthritis of the spine. METHODS: Rhumatologists included 124 patients who were randomized into two groups of 62 each. Pain was measured daily during the seven-day treatment Huskisson's Analog Visual Scales; 112 were per protocol and evaluable. RESULTS: The two treatment groups were statistically similar for demographics, vital signs, medical and treatment history. A majority of them had pain located at the lumbar spine only; the other patients had either pain at the cervical or dorsal spine or at several sites. At the end of the week there was a major reduction in pain level: 51.2% in patients given paracetamol-cafeine and 47.0% in those given paracetamol-dextropropoxyphen. The main criteria of efficacy--the percentage of success (decrease of pain > 50%)--was similar in the two groups as well in the intention-to-treat population (p = 0.01) as the per protocol population (p = 0.028). Kinetics of pain decrease during the first day of treatment were assessed with an hourly evaluation during the six first hours and at the 12th hour. There was no difference between the two groups. There was no serious adverse event and the frequency and intensity of the adverse events were similar in the two groups. CONCLUSION: The potentializing action of cafeine on paracetamol-induced pain relief enables a degree of pain relief equivalent to that of a combination using an analgesic with a peripheral action, paracetamol, and another with a central action, dextropoxyphen. The fact that the paracetamol-cafeine combination does not have a central action avoids secondary effects induced by central analgesics (drowsiness, constipation) in patients with osteoarthritis back pain.

Acetaminophen↗

Blood monocyte activation in rheumatoid arthritis: increased monocyte adhesiveness, integrin expression, and cytokine release.

Infiltration of the synovium by mononuclear cells, namely lymphocytes and monocytes, is one of the main features of rheumatoid arthritis (RA) and is considered to be responsible for the development of the disease. In this study in 31 consecutive patients with RA, we investigated whether peripheral blood monocytes exhibited markers of cellular activation related to cell migration. Using flow cytometry with the respective specific antibodies, we studied the expression of integrins CD11a, CD11b, CD11c, CD49d (VLA-4), and CD49e (VLA-5) on monocytes from patients with RA and from normal (N) subjects. IL-1 beta, IL-6, and tumour necrosis factor-alpha (TNF-alpha) production by cultured monocytes was measured by immunoassay. Adhesiveness of monocytes was studied on various surfaces (plastic, human fibronectin, gelatin-coated plasma, subendothelial matrix) and on cultured endothelial cells under basal conditions or after stimulation by IL-1 beta. An increased number of CD14+ monocytes (Mo) from RA patients expressed the CD11b molecule (RA Mo = 90.3%, N Mo = 83.4%, P < 0.005). The expression of CD11b on CD14+ monocytes was significantly increased in RA patients (median fluorescence intensity (FI): RA Mo = 145 (range 80-466) units; normal Mo = 95 (range 24-164) units; P < 0.003). Production of extracellular IL-1 beta and IL-6 by RA monocytes was significantly enhanced compared with monocytes from normal subjects (IL-1 beta: RA = 2.65 +/- 0.91 ng/ml versus N = 1.35 +/- 0.85 pg/ml, P < 0.05; IL-6: RA = 4.83 +/- 0.90 ng/ml versus N = 2.40 +/- 0.95 ng/ml, P < 0.05). Compared with normal monocytes, RA monocytes exhibited increased adhesion to the various surfaces studied (plastic, P < 0.01; fibronectin, P < 0.01; and gelatin-coated normal or RA plasma, P < 0.01) as well as to unstimulated (P < 0.01) and IL-1 beta-stimulated endothelial cells (IL-1 beta for 4 h, P < 0.05; IL-1 beta for 24h, P < 0.05). In our study, blood monocytes from RA patients exhibited features of activation related to cell adhesion.

Arthritis, Rheumatoid↗

Bone resorption at the femoral neck is dependent on local factors in nonosteoporotic late postmenopausal women: an in vitro-in vivo study.

Local mediators of bone resorption may be involved in bone loss in recently postmenopausal women and in osteoporosis. In the present study, we investigated the production of cytokines and the formation of osteoclast-like cells in marrow cultures from 16 late postmenopausal nonosteoporotic women (mean age: 66 +/- 8 years; time after menopause: 15 +/- 8 years) undergoing hip replacement for arthrosis. Marrow adherent mononuclear cells (MMNC) isolated from femoral diaphysis marrow were cultured for 10 days in the absence or in the presence of 1,25(OH)2D3. In vivo bone resorption was concomitantly assessed by histomorphometry on femoral neck bone sections. The number of TRAP+ multinucleated cells obtained after 10 days in MMNC cultured in the presence of 1,25(OH)2D3 correlated with the number of osteoclasts measured on the bone femoral neck biopsies (r = 0.65, p < 0.01), suggesting that the formation of multinucleated cells in vitro could reflect the osteoclast differentiation in vivo. Furthermore, the number of osteoclasts was related to the eroded volume and the trabecular separation of the femoral neck bone biopsies. Finally, the release of interleukin-1 (IL-1), IL-6, and TNF-alpha by cultures of peripheral blood mononuclear cells (PBMC) and MMNC was measured by radioimmunoassay. The cytokine levels of basal and 1,25(OH)2D3-treated MMNC decreased from days 2 to 5 and then reached a plateau to day 10. The number of TRAP+ multinucleated cells obtained after 10 days in MMNC cultures correlated with the basal IL-6 release in the same cultures determined at day 2 (r = 0.55, p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Absorptiometry, Photon↗

Dialysis arthropathy: outcome after renal transplantation.

PURPOSE: Patients treated by long-term maintenance hemodialysis frequently develop a form of chronic arthropathy that is strongly associated with beta 2-microglobulin amyloid deposition and related, at least in part, to beta 2-microglobulin retention. Successful renal transplantation is followed by a rapid fall in serum beta 2-microglobulin levels and might allow dissolution of amyloid deposits. The purpose of this work was to investigate the effects of renal transplantation on dialysis arthropathy. PATIENTS AND METHODS: Fourteen renal transplant recipients were selected on the basis of previous hemodialysis treatment for at least 10 years (mean 16) and a history of chronic joint pain prior to transplantation. They all received 10 to 17.5 mg/d of prednisone. Posttransplant rheumatologic manifestations were studied prospectively and compared to pretransplant rheumatologic manifestations recorded in medical charts and reported during patient interviews. Pretransplant and posttransplant articular roentgenograms were separately analyzed by three observers who were blinded to timing of the films. Beta 2-microglobulin amyloid was identified by Congo red staining and immunohistology. RESULTS: After a mean posttransplant interval of 54 months (range 12 to 121), the articular condition was improved in 10 patients, unchanged in 1, and worsened in 3, according to patients' assessments. The number of painful joints decreased significantly (P < 0.05) as compared to the pretransplant period. However, the number and size of subchondral bone erosions remained unchanged, destructive arthropathies generally worsened, and articular beta 2-microglobulin amyloid deposits were identified in 2 patients, 2 and 10 years after renal transplantation, respectively. CONCLUSION: Renal transplantation appeared to arrest progression of beta 2-microglobulin amyloid in dialysis patients, but it neither led to dissolution of deposits nor prevented progression of destructive arthropathies. Most articular symptoms were improved, probably as a result of corticosteroid therapy.

Adult↗