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Substances reactive with mannose-binding protein
(MBP) in sera of patients with rheumatoid arthritis.
Sato R; Matsushita M; Miyata M; Sato Y; Kasukawa R; Fujita
T
Department of Internal Medicine II, Fukushima Medical
College, Japan.
Fukushima J Med Sci (Japan) Dec 1997, 43 (2)
p99-111
OBJECTIVES: In order to evaluate the role of
mannose-binding protein (MBP) in rheumatoid arthritis, we
characterized MBP-binding substances in sera of patients with
this disease.
METHODS: An enzyme linked immunosorbent assay (ELISA) was
used to detect MBP-binding substances in sera of patients with
RA. We applied the sera of two RA patients to an immobilized
MBP column, and by means of both ELISA and molecular sieve
chromatography, examined the substances that bound to MBP.
MBP-MASP complexes were added to the fractions containing the
binding substances, and C4-consuming activity was
examined.
RESULTS: Sera of patients with RA showed stronger MBP
binding on ELISA than did those of normal controls. In the
case of RA sera, both IgG was IgM-RF eluted from the MBP
column, whereas with normal controls, only IgG was obtained.
The results of molecular sieve chromatography showed that the
binding substances of RA patients consisted of immune
complexes containing IgG and IgM-RF. These substances were
specifically bound to MBP, and once bound, the MBP-MASP
complexes were then able to consume C4.
CONCLUSION: MBP binds to immune complexes consisting of IgG
and IgM-RF, and probably recognizes either the mannose moiety
of IgM-RF or the N-acetyl- glucosamine of agalactosyl IgG.
When this occurs in RA patients, the lectin pathway would then
be activated.
Putative analgesic activity of repeated oral doses
of vitamin E in the treatment of rheumatoid arthritis. Results
of a prospective placebo controlled double blind trial.
Edmonds SE; Winyard PG; Guo R; Kidd B; Merry P;
Langrish-Smith A; Hansen C; Ramm S; Blake DR
Inflammation Research Group, St Bartholomew's School of
Medicine and Dentistry, London.
Ann Rheum Dis (England) Nov 1997, 56 (11)
p649-55
OBJECTIVE: Vitamin E, the most potent naturally occurring
lipid soluble antioxidant has been suggested to possess both
anti-inflammatory and analgesic activity in humans. This
double blind and randomised study used a broad spectrum of
clinical and laboratory parameters to investigate whether
there was any additional anti-inflammatory or analgesic
effects, or both, of orally administered alpha-tocopherol in
rheumatoid arthritis patients who were already receiving
anti-rheumatic drugs.
METHODS: Forty two patients were enrolled and treated with
alpha-tocopherol (n = 20) at a dose of 600 mg twice a day (2 x
2 capsules) or with placebo (n = 22) for 12 weeks. The
following parameters were measured: (1) Three clinical indices
of inflammation--the Ritchie articular index, the duration of
morning stiffness, and the number of swollen joints; (2) three
measures of pain--pain in the morning, pain in the evening,
and pain after chosen activity; (3) haematological and
biochemical measures of inflammatory activity; (4) assays for
the oxidative modification of proteins and lipids.
RESULTS: All laboratory measures of inflammatory activity
and oxidative modification were unchanged. Furthermore, the
clinical indices of inflammation were not influenced by the
treatment. However, the pain parameters were significantly
decreased after vitamin E treatment when compared with
placebo.
CONCLUSION: The results provide preliminary evidence that
vitamin E may exert a small but significant analgesic activity
independent of a peripheral anti-inflammatory effect, but
which complements standard anti-inflammatory treatment.
Renal stones in patients with rheumatoid
arthritis.
Ito S; Nozawa S; Ishikawa H; Tohyama C; Nakazono K; Murasawa
A; Nakano M; Arakawa M
Department of Medicine, Niigata Prefectural Senami Hospital,
Niigata University School of Medicine, Japan.
J Rheumatol (Canada) Nov 1997, 24 (11) p2123-8
OBJECTIVE: Renal stones are reported to be one of the
causes of hematuria in patients with juvenile rheumatoid
arthritis (RA). We performed abdominal ultrasonography on
patients with RA to investigate the frequency of renal stones
and whether renal stones are related to hematuria.
METHODS: We conducted abdominal ultrasonography in 224
patients with RA (42 men, 182 women). Mean age was 61.4 years,
and the mean duration of disease was 13.5 years.
RESULTS: Renal stones were defined as hyperechoic spots
with acoustic shadows, and they were observed in 37 patients.
We also noticed hyperechoic spots without acoustic shadows in
50 patients. Five of these 50 patients also had renal stones.
Twenty-one patients showing hyperechoic spots without acoustic
shadows underwent computed tomographic scans, and apparent
calcifications were observed in 10 patients. Age and sex
matched controls had a significantly lower incidence of renal
stones and hyperechoic spots without acoustic shadows than did
patients with RA. Hematuria was more frequently observed in
patients with RA with renal stones than in those without renal
stones or hyperechoic spots without acoustic shadows. Urinary
calcium/creatinine (Ca/Cr) ratios were elevated in patients
compared to controls. Urinary Ca/Cr ratios in patients taking
vitamin D3 were higher than those of patients not receiving
the vitamin . Administration of vitamin D3 also was associated
with increased incidence of renal stones.
CONCLUSION: We observed a high incidence of renal stones in
patients with RA. Hematuria was more prevalent in patients
with RA with renal stones than in those without. These results
suggest the importance of performing abdominal ultrasonography
on patients with RA.
[Inflammation and bone metabolism in rheumatoid
arthritis. Pathogenetic viewpoints and therapeutic
possibilities]
Oelzner P; Hein G
Klinik fur Innere Medizin IV, Friedrich-Schiller-Universitat
Jena.
Med Klin (Germany) Oct 15 1997, 92 (10) p607-14
BACKGROUND: Systemic osteoporosis is a common and
pathogenetically heterogenous complication in rheumatoid
arthritis. Various factors such as disease activity, dosage
and duration of glucocorticoid treatment and immobilization
are involved in pathogenesis of osteoporosis in rheumatoid
arthritis.
INFLAMMATION AND BONE METABOLISM: Proinflammatory cytokines
secreted by immunocompetent cells have a role in the
regulation of the activity of osteoblasts and osteoclasts. The
effects of these proinflammatory cytokines include the
inhibition of bone formation and an increase in bone
resorption. Interleukin-6 and nitric oxide induced in
osteoblasts by proinflammatory cytokines are likely to be
important mediators between these cytokines and the function
of osteoblasts and osteoclasts. Furthermore, disease activity
dependent changes in the secretion of glucocorticoids and in
vitamin D metabolism may be involved in the pathogenesis of
osteoporosis in this disease. Alteration of bone remodeling
associated with immobilization is an important factor of
systemic bone loss in rheumatoid arthritis.
CONCLUSION: The inflammatory process in rheumatoid
arthritis may cause penarticular and systemic bone loss by
various cytokine and hormone mediated mechanisms. Concluding
from these pathogenetic mechanisms, bisphosphonates and active
vitamin D metabolites are likely to be effective therapeutic
options in osteoporosis associated with rheumatoid arthritis.
(106 Refs.)
Predictors of total body bone mineral density in
non-corticosteroid-treated prepubertal children with juvenile
rheumatoid arthritis.
Henderson CJ; Cawkwell GD; Specker BL; Sierra RI; Wilmott RW;
Campaigne BN; Lovell DJ
Children's Hospital Medical Center, Cincinnati, Ohio 45229,
USA.
Arthritis Rheum (United States) Nov 1997, 40 (11)
p1967-75
OBJECTIVE: To determine the extent of significant
osteopenia in prepubertal patients with juvenile rheumatoid
arthritis (JRA) not treated with corticosteroids and to
identify variables that are highly related to bone
mineralization in this population.
METHODS: In a cross-sectional study, 48 JRA patients and 25
healthy control subjects ages 4.6-11.0 years were evaluated.
Total body bone density (TB BMD) was determined by Hologic
dual energy x-ray absorptiometry. All patients were
prepubertal (Tanner stage I or II) and had never taken
corticosteroids. For comparison, JRA patients were divided
into "low" TB BMD (Z score < or =-1) or "normal" TB BMD (Z
score >-1).
RESULTS: The overall mean +/- SD TB BMD scores did not
differ between the JRA subjects (0.75 +/- 0.06 gm/cm2) and
controls (0.73 +/- 0.07 gm/cm2; P > 0.30). However, 29.2%
of the JRA patients had low TB BMD, whereas only 16% would be
expected to have low TB BMD based on the standard normal
distribution (goodness of fit chi(2) = 4.84, P = 0.01). The
mean Z score for the JRA patients with low TB BMD was -1.43,
and for those with normal TB BMD, it was 0.32. The JRA
subjects with low TB BMD were significantly younger, had more
active articular disease, greater physical function
limitation, higher erythrocyte sedimentation rate, higher
joint count severity score, lower body mass index, lower lean
body mass, less participation in organized sports, and more
protein and vitamin D in their diet compared with JRA patients
with normal TB BMD (all P < 0.05). Using logistic
regression, a model including age at JRA onset, Juvenile
Arthritis Functional Assessment Report (JAFAR) score, triceps
skin-fold percentiles, percentage US recommended daily
allowance for dietary magnesium intake, and serum
1,25-dihydroxyvitamin D levels was able to accurately
segregate 79.6% of the JRA subjects into either the low or
normal TB BMD groups (chi(2) = 20.5, P = 0.001).:
CONCLUSION This study demonstrated that in a mildly to
moderately ill prepubertal JRA population that had never been
exposed to corticosteroids, almost 30% had significantly low
TB BMD. The patients with low TB BMD had more active and
severe articular disease and greater physical function
limitation. Disease-related parameters in JRA appear to exert
a negative effect on bone mineralization even in prepubertal
children, which can be demonstrated despite the exclusion of
corticosteroid-treated patients.
Nutrient intake patterns, body mass index, and
vitamin levels in patients with rheumatoid arthritis.
Morgan SL; Anderson AM; Hood SM; Matthews PA; Lee JY; Alarcon
GS
Department of Nutrition Sciences School of Medicine,
University of Alabama at Birmingham 35294-3360, USA.
Arthritis Care Res (United States) Feb 1997, 10 (1)
p9-17
OBJECTIVE: To assess nutrient intakes and vitamin levels in
79 patients with rheumatoid arthritis participating in a trial
and to determine whether changes in body mass index were
associated with changes in disease activity.
METHODS: This study evaluated baseline vitamin levels,
1-day dietary intakes, and weight every 3 months for 1 year.
Linear regression analysis was used to evaluate the
relationship of time to body mass index. Analysis of
covariance was used to determine if body mass index, time, or
treatment had an effect on disease activity.
RESULTS: Deficient vitamin levels and poor nutrient intake
patterns were prevalent in the study population. Changes in
body mass index over time did not correlate with changes in
disease activity.
CONCLUSIONS: Rheumatoid arthritis patients are at high risk
of obesity, abnormal vitamin levels, and poor nutrient
intakes. Changes in body mass index failed to correlate with
changes in disease activity.
Effects of low dose methotrexate on the bone
mineral density of patients with rheumatoid arthritis.
Buckley LM; Leib ES; Cartularo KS; Vacek PM; Cooper SM
Division of Rheumatology, Allergy and Immunology, Medical
College of Virginia, Virginia Commonwealth University,
Richmond 23219, USA.
J Rheumatol (Canada) Aug 1997, 24 (8) p1489-94
OBJECTIVE: To determine the effects of low dose
methotrexate (MTX) on bone mineral density (BMD) of patients
with rheumatoid arthritis (RA).
METHODS: We examined the relationship between BMD and
disease modifying antirheumatic drug (DMARD) use with data
from a prospective, randomized, placebo controlled trial
assessing the effects of calcium and vitamin D3
supplementation on BMD of patients with RA. Measurements of
BMD of the lumbar spine and femoral neck were performed at
baseline and at yearly followup visits over 3 years.
RESULTS: Information about DMARD use and BMD was available
for 133 patients at baseline, and for 95 patients at Year 3.
Lumbar spine and femoral neck BMD of MTX and non-MTX treated
patients were similar at the start of the study. At the end of
3 years of followup, there was no significant differences in
the change in BMD of the femoral neck and lumbar spine in MTX
and non-MTX treated patients, in general. However, patients
treated with prednisone > or = 5 mg/day plus MTX had
greater loss of BMD in the lumbar spine than patients treated
with a similar dose of prednisone without MTX (difference
-8.08% over 3 years; p = 0.004).
CONCLUSION: At the end of 3 years, low dose MTX use was not
associated with change in femoral neck or lumbar spine BMD in
patients who were not treated with corticosteroids. However,
among patients treated with prednisone > or = 5 mg/day,
combined treatment with MTX and prednisone was associated with
greater bone loss in the lumbar spine than treatment with
prednisone without MTX.
Correlation between blood antioxidant levels and
lipid peroxidation in rheumatoid arthritis.
Gambhir JK; Lali P; Jain AK
Department of Biochemistry, University College of Medical
Sciences, Shahdara, Delhi.
Clin Biochem (United States) Jun 1997, 30 (4)
p351-5
OBJECTIVES: To investigate the relationship between lipid
peroxidation and certain antioxidant parameters in the blood
of rheumatoid arthritis patients.
METHODS AND RESULTS: In the present study, significantly
increased lipid peroxidation, measured as malondialdehyde
(MDA), was demonstrated in the plasma of rheumatoid arthritis
patients (p < 0.01). The activities of erythrocyte
antioxidant enzymes, superoxide dismutase and catalase
remained unaltered. However, erythrocyte glutathione and
plasma ceruloplasmin levels were significantly higher in
patients (p < 0.001). Moreover, a positive correlation was
also observed between these two parameters and MDA levels in
the patient group but not in controls. Interestingly, a
significant positive correlation also existed between red cell
glutathione and plasma ceruloplasmin levels.
CONCLUSION: These results suggest that increased oxidant
stress present in rheumatoid arthritis may lead to
compensatory changes in the levels of some antioxidants, viz.
glutathione and ceruloplasmin. These changes, in turn, may
provide additional protection against lipid peroxidation in
rheumatoid arthritis.
Emerging treatments for rheumatoid arthritis.
Schiff M
Clinical Research Unit, Denver Arthritis Clinic, Colorado
80220, USA.
Am J Med (United States) Jan 27 1997, 102 (1A)
p11S-15S
Rheumatoid arthritis was considered for centuries to be a
nuisance condition, limiting in its effects on an individual's
range of motion and the source of considerable distress, but
not a life-threatening disease. Recently, however, it has
become apparent that patients with severe rheumatoid arthritis
may have a decreased life span. Current pharmacologic
therapies for patients with rheumatoid arthritis, which
include nonsteroidal anti-inflammatory drugs,
disease-modifying antirheumatic drugs, methotrexate, and
corticosteroids, have been moderately successful in
alleviating the discomforts associated with swollen, painful
joints. Many practitioners have sought to improve use of these
agents and slow joint destruction by challenging traditional
treatment paradigms, altering the sequence in which drugs are
given. Nevertheless, most standard medical approaches to
treatment have had little or no impact on the course of
rheumatoid disease. Innovative strategies, particularly those
based on new concepts in the immunobiology of rheumatoid
arthritis, are being developed to target cellular inflammatory
mechanisms and actually prevent disease progression. Some
agents, such as inhibitors of 5-lipoxygenase-omega-3 fatty
acid and zileuton-may be most useful in treatment of milder
disease manifestations such as moderate synovitis. Other
agents, such as oral type II collagen, minocycline,
subcutaneous interleukin-1ra, and anti-CD4 monoclonal
antibodies, have produced such inconsistent results that
substantial additional research will be required before any
conclusions may be drawn about their value. Among the most
promising agents, and the most extensively studied, are tumor
necrosis factor-alpha monoclonal antibodies, immunosuppressive
drugs such as cyclosporine and mycophenolate mofetil, and the
novel compound tenidap, which has both cytokine-modulating and
anti-inflammatory properties. (38 Refs.)
Zinc metabolism in rheumatoid arthritis: plasma and
urinary zinc and relationship to disease activity
Naveh Y; Schapira D; Ravel Y; Geller E; Scharf Y
Department of Pediatrics, Rambam Medical Center, Haifa,
Israel.
J Rheumatol (Canada) Apr 1997, 24 (4) p643-6
OBJECTIVE: To study zinc absorption in patients with active
rheumatoid arthritis (RA).
METHODS: We studied zinc tolerance tests and 24 hour
urinary zinc excretion before and after ingestion of 50 mg
elemental zinc in 8 healthy volunteers (Group 1) and 13
patients with low RA activity (Group 2) and 16 patients with
high RA activity (Group 3).
RESULTS: In Group 1, plasma zinc rose from 111 +/- 7
micrograms/dl to a peak of 200 +/- 24 micrograms/dl (mean +/-
SEM) in 2 h. In Groups 2 and 3, plasma zinc before zinc
ingestion was significantly lower than that of the control
group (p < 0.00001 for both groups) and showed no
significant increase in plasma after ingestion. Twenty-four
hour urinary zinc excretions before and after zinc ingestion
were significantly lower (p < 0.01, p < 0.0001 for Group
2; p < 0.05, p < 0.01 for Group 3, respectively) than
those in the control group.
CONCLUSION: These results are compatible with zinc
malabsorption and consequent zinc deficiency in patients with
RA. Whether zinc deficiency contributes to perpetuation of
disease activity by compromising cellular immune function
needs further investigátion.
Incruased serum NG-hydroxy-L-arginine in patients
with rheumatoid arthritis and systemic lupus erythematosus as
an index of an increased nitric oxide synthase activity.
Wigand R; Meyer J; Busse R; Hecker M
Centre of Physiology, Johann Woifgang Goethe University
Clinic, Frankfurt Main, Germany.
Ann Rheum Dis (England) May 1997 56 (5) p330-2
OBJECTIVES: To determine the feasibility of monitoring the
serum concentration of NG-hydroxy-L-arginine (L-NHA) as an
index of an increased nitric oxide (NO) synthase activity in
patients with rheumatoid arthritis (RA) and systemic lupus
erythematosus (SLE) compared with nitrate (NO3-), the major
circulating metabolite of NO whose concentration is influenced
by dietary intake.
METHODS: The serum concentrations of L-NHA, L-arginine
(L-Arg), and NO3- were determined in 33 patients with RA, 25
patients with SLE and, 29 healthy subjects.
RESULTS: Serum L-NHA was significantly increased in RA
patients with high disease activity (287% of control, p <
0.01), but not with low disease activity (115%), as well as in
patients with SLE (173%, p < 0.01). In contrast, serum NO3-
did not differ significantly between either group of patients
and the respective control group.
CONCLUSION: NO synthase activity or expression, or both, is
upregulated in RA patients with high disease activity and in
patients with SLE. Serum L-NHA seems to be a more specific and
reliable index of an increased activity of this enzyme in
patients with acute or chronic inflammatory diseases than
NO3-.
Management of oral complications of
disease-modifying drugs in rheumatoid arthritis.
Carpenter EH; Plant MJ; Hassell AB; Shadforth MF; Fisher J;
Clarke Ó; Hothersall TE; Dawes PT
Staffordshire Rheumatology Centre, Haywood Hospital,
Stoke-on-Trent.
Br J Rheumatol (England) Apr 1997, 36 (4) p473-8
Stomatitis is a troublesome adverse effect of
disease-modifying anti-rheumatic drug (DMARD) therapy in
rheumatoid arthritis (RA) patients. This review presents data
to examine the incidence, clinical features and consequences
of DMARD-related stomatitis, and suggests an algorithm for its
clinical management. The specific objectives of the two
studies presented here were to determine the incidence of
DMARD-related stomatitis and its effect on DMARD continuation,
and secondly to identify the clinical and laboratory risk
factors. We investigated two cohorts of patients: (i) a
retrospective survey of data collected from drug monitoring
clinics run for patients on DMARDs from 1987 to 1994 involving
1539 patients and 2394 drug exposures; (ii) a prospective
study of 25 consecutive RA patients presenting with
DMARD-related stomatitis compared to 29 RA controls with no
history of DMARD stomatitis. The retrospective survey showed
that 2% of DMARD patients stopped therapy because of
stomatitis, but 55% of these were able to resume the same
therapy. In the case control study. 24% of patients
discontinued temporarily and 8% permanently. Cases of
DMARD-related stomatitis differed from controls in that they
had a higher incidence of previous mouth ulcers (40% vs 14%),
they smoked less (8% vs 31%) and Schirmer's test was more
often abnormal (44% vs 21%). There were no differences in RA
severity, disease activity or oral hygiene. Haematinic
deficiencies were equally common in cases and controls: 30%
for iron, 8% for vitamin B12 and 24% for folic acid. Herpes
simplex virus was involved in a minority (8%) of cases. In
conclusion, the occurrence of stomatitis in RA patients on
DMARD should not lead to cessation of drug therapy, but to a
careful evaluation so that patients may be maintained on
effective treatment.
Comparison between intravenous and subcutaneous
recombinant human erythropoietin (Epoetin alfa) administration
in presurgical autologous blood donation in anemic rheumatoid
arthritis patients undergoing major orthopedic surgery.
Mercuriali F; Inghilleri G; Biffi E; Colotti MT; Vinci A;
Sinigaglia L; Gualtieri G
Istituto Ortopedico Gaetano Pini, Milano, Italia.
Vox Sang (Switzerland) 1997, 72 (2) p93-100
BACKGROUND AND OBJECTIVES: Intravenous (i.v.) Recombinant
erythropoietin (Epoetin alfa) is effective in allowing
autologous blood donation in patients unable to donate because
of anemia. We undertook this open pilot study in order to
asses whether a low subcutaneous (s.c.) dose of Epoetin alfa
would prove as effective and well tolerated as the higher i.v.
dose. Such a move would also decrease costs.
MATERIALS AND METHODS: A total Epoetin alfa s.c. dose of
800 IU/kg was compared with a total i.v. dose of 1,800 IU/kg.
Twenty-two rheumatoid arthritis patients, unable to donate
because of hemoglobin (Hb) < 11 g/dl, received 300 IU/kg of
IV Epoetin alfa twice weekly for 3 weeks (11 patients), or 100
IU/kg of s.c. Epoetin alfa twice weekly for 3 weeks plus an
i.v. bolus of 200 IU/kg of Epoetin alfa at the first visit (11
patients). At each visit, all patients received 100 mg of i.v.
iron saccharate and when the hematocrit (hct) > or = 34%,
350 ml of autologous blood (AB) were collected.
RESULTS: No significant differences were observed between
the 2 groups of treated patients in terms of units of AB
collected (2.6 +/- 0.6 vs. 2.5 +/- 0.5 units for i.v. and s.c.
groups, respectively), ml of RBC produced during the study
period (291 +/- 99 vs. 337 +/- 65 ml for the i.v. and s.c.
groups, respectively), or in the degree of reduced exposure to
allogeneic blood in comparison with the control group.
CONCLUSIONS: Lower dose of Epoetin alfa (reduced by 56%),
supplemented by i.v. iron, is as effective and well tolerated
as higher doses administered i.v., supplemented by i.v. iron
.
Abnormal homocysteine metabolism in rheumatoid
arthritis.
Roubenoff R; Dellaripa P; Nadeau MR; Abad LW; Muldoon BA;
Selhub J; Rosenberg IH
Jean Mayer USDA Human Nutrition Research Center on Aging at
Tufts University, Boston, MA 02111, USA.
Arthritis Rheum (United States) Apr 1997, 40 (4)
p718-22
OBJECTIVE: To assess total homocysteine (tHcy) metabolism
in patients with rheumatoid arthritis (RA).
METHODS: Assessments were performed to determine the
fasting levels of tHcy and the increase in tHcy in response to
methionine (Met) challenge in blood samples from 28 patients
with RA and 20 healthy age-matched control subjects.
RESULTS: Fasting levels of tHcy were 33% higher in the RA
patients than in the control subjects (mean +/- SD 11.7 +/-
1.5 nmoles/ml versus 8.8 +/- 1.1 nmoles/ml; P < 0.01). Four
hours after Met challenge, the increase in plasma tHcy levels
(delta tHcy) was higher in the RA patients (20.9 +/- 10.4
nmoles/ml) than in the control subjects (15.5 +/- 1.6
nmoles/ml) (P < 0.02). In a subgroup analysis, the delta
tHcy in patients taking methotrexate (12.9 +/- 2.2 nmoles/ml)
did not differ from that in the control group, while the delta
tHcy in patients not taking methotrexate (25.3 +/- 1.7
nmoles/ml) was significantly higher (P < 0.0001).
CONCLUSION: Elevated tHcy levels occur commonly in patients
with RA, and may explain some of the increased cardiovascular
mortality seen in such patients. Studies of the prevalence and
mechanism of hyperhomocysteinemia in RA are warranted.
Prediction of articular destruction in rheumatoid
arthritis: disease activity markers revisited
Coste J; Spira A; Clerc D; Paolaggi JB
Departement de Biostatistique et d'Informatique Medicale,
Hopital Cochin, Paris, France.
J Rheumatol (Canada) Jan 1997, 24 (1) p28-34
OBJECTIVE: To assess the predictive value for joint damage
progression of commonly used disease activity or process
measures in rheumatoid arthritis (RA).
METHODS: Seventy-two patients fulfilling the American
Rheumatism Association criteria for RA were assessed twice
yearly for 2 years. Primary outcome variables were progression
of articular destruction, evaluated by Sharp's method, for 6,
12, 18, and 24 month periods.
RESULTS: Regression analysis, using random effects linear
models, showed that only C-reactive protein, alpha 1-acid
glycoprotein, iron, and erythrocyte sedimentation rate were
significantly, but not independently, associated with 6 month
radiographic progression. Traditional clinical measures were
not predictive. No assessed marker was able to predict longer
term outcome (12 or 18 month joint damage progression). Recent
onset disease and older age were also associated with more
severe radiographic progression.
CONCLUSION: The lack of association between clinical
measures and laboratory markers as predictors of the
progression of articular destruction is further evidence of
the need to reconsider processes and outcomes in RA. This
study also suggests that clinical measures and laboratory
markers probably do not reflect the same underlying process,
arguing against gathering these measures under the same
heading of "disease activity measures".
Intractable diarrhoea associated with secondary
amyloidosis in rheumatoid arthritis.
Okuda Y; Takasugi K; Oyama T; Oyama H; Nanba S; Miyamoto
T
Department of Internal Medicine, Dohgo Spa Hospital, Ehime,
Japan.
Ann Rheum Dis (England) Sep 1997, 56 (9) p535-41
OBJECTIVE: To examine the clinical characteristics of
intractable diarrhoea associated with secondary amyloidosis in
rheumatoid arthritis (RA).
METHODS: Of 179 RA patients with biopsy confirmed secondary
amyloidosis, 24 cases (23 women and one man) with intractable
diarrhoea lasting for more than one month were retrospectively
evaluated.
RESULTS: The mean (SD) duration of diarrhoea was 87 (64)
days. Prodromal symptoms of gastrointestinal dysfunction (n =
21) and impaired peristalsis (n = 16) were observed.
Laboratory data showed hypoproteinaemia (4.7 (0.85) g/dl)
caused by malabsorption or protein loss and high values of C
reactive protein (17.0 (9.3) mg/dl). Recurrence of intractable
diarrhoea (n = 4) and transition from intractable diarrhoea to
other gastrointestinal problems of amyloidosis (ischaemic
colitis (n = 2) and intestinal pseudo-obstruction (n = 4))
were observed. In 19 patients (25 episodes) the duration of
intravenous hyperalimentation at remission (18 episodes) was
68 (52) days. Corticosteroid pulse therapy was administered to
10 patients (11 times) and the time elapsed from the end of
corticosteroid pulse therapy to the end of diarrhoea was 18
(14) days. One and five year survival rates after the onset of
intractable diarrhoea were 73.4% and 38.9%. Seven of 13
patients (54%) had died as a result of infectious
diseases.
CONCLUSION: Intractable diarrhoea associated with secondary
amyloidosis in RA is a serious clinical entity and the
prognosis is poor. Although it is assumed that intravenous
hyperalimentation treatment and corticosteroid pulse therapy
are favourable regimens for intractable diarrhoea, the
patients should be monitored for possible infectious
complications.
An open study of the anti-TNF alpha agent
pentoxifylline in the treatment of rheumatoid arthritis.
Dubost JJ; Soubrier M; Ristori JM; Beaujon G; Oualid T;
Bussiere JL; Sauvezie B
Clinical Immunology Unit, Gabriel-Montpied Hospital,
Clermont-Ferrand, France.
Rev Rhum Engl Ed (France) Dec 1997, 64 (12)
p789-93
OBJECTIVE: Monoclonal antibodies to TNF alpha have a rapid
therapeutic effect in rheumatoid arthritis. Pentoxifylline is
an anti-TNF alpha agent that is easier to handle than
antibodies.
METHODS: An open prospective trial was conducted in 21
patients with active rheumatoid arthritis. Pentoxifylline was
given in a daily dosage of 1,200 mg for at least one month.
Five patients received the drug as a continuous intravenous
infusion during the first seven days.
RESULTS: After one month, a significant decrease in the
pain severity score was noted, but all other clinical and
laboratory efficacy parameters were unchanged. A limited
response was seen in four patients. TNF alpha levels did not
decrease under therapy.
CONCLUSION: Under the conditions of our trial, the
therapeutic benefits provided by pentoxifylline were too small
to warrant use of this drug in severe refractory rheumatoid
arthritis.
Life-table analysis of cyclosporin A treatment in
psoriatic arthritis: comparison with other disease-modifying
antirheumatic drugs.
Spadaro A; Taccari E; Mohtadi B; Riccieri V; Sensi F; Zoppini
A
Institute of Rheumatology, University La Sapienza, Rome,
Italy.
Clin Exp Rheumatol (Italy) Nov-Dec 1997, 15 (6)
p609-14
OBJECTIVES: The aim of this study was to determine the
cumulative probability of taking CsA in comparison to other
DMARDs, as well as the reason for discontinuation of each
DMARD, in a large cohort of PsA patients.
METHODS: We prospectively studied 172 consecutive patients
with a diagnosis of PsA who had been admitted to our
rheumatological unit since 1984. We collected information
about treatment with DMARDs including: number, dose, duration
and causes of withdrawal, including side effects or
inefficacy. Cumulative survival analysis was performed by the
Kaplan-Meier test and the differences between these survival
curves were determined by the Mantel-Hanszel test.
RESULTS: The probability curve of continuing to take CsA
was significantly lower than that of MTX (p < 0.046). The
rate of adverse effects responsible for stopping DMARD therapy
was higher in the CsA group, especially with respect to the
antimalarial group (p < 0.014). The most common cause of
CsA withdrawal was hypertension. The rate of withdrawal due to
inefficacy in the CsA group was not significantly different
from those observed in the other groups. Nevertheless, the
total frequency of discontinuation due to toxicity and
inefficacy in the MTX group was significantly lower compared
to the gold salts (p < 0.05) and CsA groups (p <
0.01).
CONCLUSION: Life-table analysis suggests that PsA patients
taking CsA are less likely than patients on MTX to continue
long term treatment. Therefore CsA, which seems to be less
safe than the antimalarials, could be considered a useful drug
in the treatment of PsA, but does seem to represent the drug
of first choice, particularly when compared to MTX.
Methotrexate as the initial second-line disease
modifying agent in the treatment of rheumatoid arthritis
patients.
Bologna C; Jorgensen C; Sany J
Service d'Immuno-Rhumatologie, CHU Lapeyronie, Montpellier,
France.
Clin Exp Rheumatol (Italy) Nov-Dec 1997, 15 (6)
p597-601
OBJECTIVE: To assess the efficacy and toxicity profile of
methotrexate (MTX) as the initial second-line disease
modifying anti-rheumatic drug (DMARD) in rheumatoid arthritis
(RA).
METHODS: This was an observational retrospective cohort
study comparing 28 patients who were treated with MTX as the
first DMARD (MTX cases) and 55 matched patients treated with
MTX after other DMARDs (MTX controls).
RESULTS: The follow-up time was identical in the two
groups: 19.4 +/- 14 months (2-56) for the MTX cases and 21.8
+/- 15.3 months (3-87) for MTX controls (NS). MTX efficacy was
the same in the two groups, except for a higher incidence of
remission in the MTX cases (8/28, 28.6% versus 5/55, 9.1%, p =
0.028). The toxicity profiles, frequencies, and reasons for
MTX withdrawals were similar in the two groups.
CONCLUSION: The results obtained in this study suggest a
benefit from MTX prescribed as an initial second-line agent in
the treatment of RA, but studies involving a larger number of
patients are needed.
The relationship between variations in knee
replacement utilization rates and the reported prevalence of
arthritis in Ontario, Canada.
Coyte P; Wang PP; Hawker G; Wright JG
Department of Health Administration and Institute for Policy
Analysis, University of Toronto, Ontario, Canada.
J Rheumatol (Canada) Dec 1997, 24 (12) p2403-12
OBJECTIVE. To determine the relationship between regional
variations in knee replacement (KR) utilization rates in
Ontario, Canada, and the reported prevalence of arthritis and
rheumatism as a chronic health problem.
METHODS. Utilization data were acquired from the Canadian
Institute for Health Information for KR procedures performed
in Ontario between fiscal years 1984 and 1990. Census
information was obtained from Statistics Canada. Disease
prevalence data were derived from the 1990 Ontario Health
Survey (OHS). Public Health Units (PHU) were used as the unit
of analysis, with utilization rates defined as the number of
KR performed on all PHU residents (irrespective of where these
procedures were performed) divided by the population. Direct
methods were used to standardize utilization for age, sex, and
disease prevalence. The extremal quotient, the weighted
coefficient of variation, and the systematic component of
variation were used as measures of variation. The relationship
between the number of KR performed in each age-sex-year strata
and various demographic (age and sex), disease prevalence, and
regional dummy variables was estimated using a Poisson
regression model.
RESULTS. Regional variation in the standardized utilization
of KR surgery was wide, but declined over the study period;
the extremal quotient fell from 8.0 to 3.3, the weighted
coefficient of variation fell from 0.49 to 0.30, and the
systematic component of variation fell from 0.20 to 0.17.
Variation in the provision of KR surgery remained even after
controlling for the demographic composition of the population
and disease prevalence. Moreover, while demographic, regional,
and temporal covariates were significant (p < 0.0001) in
accounting for over 90% of the variation in utilization,
disease prevalence was not significant (p > 0.05).
CONCLUSION. This study merged population based reports of
disease prevalence with administrative data to account for
regional variations in utilization. While regional variations
in KR surgery have fallen over time, variations remain even
after adjusting for patient reported disease prevalence. The
finding that demographic variables and the reported prevalence
of disease were poorly correlated suggests that current area
variation studies may not be adjusting fully for disease
prevalence or severity.
Differences in the use of second-line agents and
prednisone for treatment of rheumatoid arthritis by
rheumatologists and non-rheumatologists.
Criswell LA; Such CL; Yelin EH
Rosalind Russell Medical Research Center for Arthritis,
Department of Medicine, University of California, San
Francisco, USA.
lac@itsa.ucsf.edu
J Rheumatol (Canada) Dec 1997, 24 (12) p2283-90
OBJECTIVE. To compare the use of methotrexate (MTX),
intramuscular (i.m.) gold, hydroxychloroquine, and prednisone
for rheumatoid arthritis (RA) treatment among patients managed
by rheumatologists and nonrheumatologists.
METHODS. Multiple regression analysis to estimate the
likelihood of starting treatment and response to treatment for
patients managed by rheumatologists and nonrheumatologists.
All regression analyses were adjusted for patient demographic
and clinical characteristics.
RESULTS. Therapy with all agents studied was initiated more
frequently for patients with RA with at least some contact
with rheumatologists during the year than for those managed
strictly by nonrheumatologists. The adjusted odds ratios for
starts on these medications ranged from 1.14 for im gold to
15.11 for MTX for patients managed by rheumatologists compared
to those managed by nonrheumatologists. However, due to the
low frequency of initiation of treatment with most of these
drugs for patients managed strictly by nonrheumatologists,
only the odds ratio for prednisone reached statistical
significance (OR = 2.94, p = 0.0082). In the year after
initiation of therapy with these agents, patients managed by
rheumatologists experienced better response to treatment than
those managed by nonrheumatologists. These differences were
statistically significant for MTX (p = 0.0447) and nearly
significant for im gold (p = 0.0597).
CONCLUSION. These results provide evidence of systematic
differences in the propensity of rheumatologists and
nonrheumatologists to initiate therapy with these
antirheumatic drugs. If the observed differences in initial
response to treatment translate into substantial differences
in longterm outcomes, then these results suggest that the
welfare of patients with RA may be jeopardized by the current
trend toward primary care and restricted access to
rheumatologists.
Destruction of the first carpometacarpal joint
behaves differently from that of the entire carpus in
rheumatoid arthritis. A 20-year follow-up study.
Belt EA; Kaarela K; Lehto MU; Kautiainen HJ; Kauppi MJ
Rheumatism Foundation Hospital, Heinola, Finland.
Scand J Rheumatol (Norway) 1997, 26 (5) p361-3
The aim of our study was to examine the radiographic
changes of the wrist and the first carpometacarpal (CMC I)
joints in rheumatoid arthritis (RA) occurring over 20 years.
The wrists of 83 RF positive RA patients with recent (< or
= 6 months) arthritis were evaluated radiographically at
onset, at 1, 3, 8, and 15 years and of 68 patients 20 years
from entry. In hands where wrist fusion was performed,
follow-up continued until the arthrodesis. Larsen grading for
the wrist joints and modified grades for the ipsilateral CMC I
joints were compared. Larsen grades of both wrists differed
highly significantly (p < 0.001) from the grades of the
ipsilateral CMC I joints after 3 years and up to end of the
study. In conclusion destruction of the CMC I does not proceed
uniformly with destruction of the entire carpus and it would
be beneficial to classify it separately.
Combination treatment of severe rheumatoid
arthritis with cyclosporine and methotrexate for forty-eight
weeks: an open-label extension study. The
Methotrexate-Cyclosporine Combination Study Group.
Stein CM; Pincus T; Yocum D; Tugwell P; Wells G; Gluck O;
Kraag G; Torley H; Tesser J; McKendry R; Brooks RH
Vanderbilt University, Nashville, Tennessee 37232, USA.
Arthritis Rheum (United States) Oct 1997, 40 (10)
p1843-51
OBJECTIVE: To determine whether the clinical benefit and
favorable safety profile previously noted with the combination
of cyclosporine (CSA) and methotrexate (MTX) given for 24
weeks in patients with rheumatoid arthritis (RA) would be
maintained for a further 24 weeks, and whether the addition of
CSA in patients who had previously been randomized to receive
placebo + MTX would result in clinical benefit .
METHODS: Eligible subjects from the initial study (weeks
0-24), in which the addition of placebo or CSA to MTX therapy
was compared in patients with RA that was partially responsive
to MTX, were enrolled. Patients who had received CSA + MTX
continued this regimen for a further 24 weeks (weeks 24-48)
(group 1; n = 48), and patients who had initially received
placebo + MTX now received CSA + MTX for 24 weeks (weeks
24-48) (group 2; n = 44), in an open-label extension study.
The primary outcome measures were the number of tender joints,
number of swollen joints, physician and patient global
assessments, pain, functional disability as measured by the
modified Health Assessment Questionnaire, and erythrocyte
sedimentation rate.
RESULTS: Of the 92 patients enrolled, 80 (87%) completed
the extension study. In patients in group 1, the clinically
and statistically significant improvement in response outcomes
previously noted at week 24, ranging from 25% to 50%, was
maintained through week 48. In patients in group 2, the
addition of CSA resulted in significant clinical improvement.
By week 48, most outcome measures in group 2 patients were
similar to those in group 1 patients. CSA treatment resulted
in a small increase in serum creatinine levels, but only 1
patient was withdrawn from the study for this reason.
CONCLUSION: The clinical improvement previously observed in
patients treated with the CSA + MTX combination for 24 weeks
was maintained for 24 subsequent weeks, without serious
adverse effects, and was also observed in the patients whose
treatment was switched from placebo + MTX to CSA + MTX.
Patient education and disease activity: a study
among rheumatoid arthritis patients.
Brus HL; Taal E; van de Laar MA; Rasker JJ; Wiegman O
Department of Rheumatology, Medisch Spectrum Twente,
Enschede, The Netherlands.
Arthritis Care Res (United States) Oct 1997, 10 (5)
p320-4
OBJECTIVE: To determine whether patients experiencing high
disease activity derive more benefit from patient education
than those experiencing low disease activity.
METHODS: Data from a randomized study on the effects of a
program of patient education were analyzed retrospectively.
Four subgroups were studied: the high disease activity
subgroup of patients who had participated in the educational
program, the complementary low disease activity subgroup, the
high disease activity subgroup of controls, and its low
disease activity complement. Patients with erythrocyte
sedimentation rate > 28 mm/first hour were classified as
having high disease activity. Effects on frequency of physical
exercises, endurance exercises, and relaxation exercises and
effects on health status (Modified Health Assessment
Questionnaire, Dutch Arthritis Impact Measurement Scales
[AIMS]) were measured.
RESULTS: There were no significant differences between the
adherence parameters of the various pairs of groups. Four
months after the educational program began, anxiety and
depression scores on the Dutch-AIMS had increased among
participating patients who were experiencing high disease
activity and decreased among those who were experiencing low
disease activity.
CONCLUSIONS: Patients experiencing high disease activity
did not derive more benefit from patient education than those
experiencing low disease activity. On the contrary, an
increase of anxiety and depression is found in these patients.
Further study is needed to confirm our findings.
Acetabular pressures during hip arthritis
exercises.
Tackson SJ; Krebs DE; Harris BA
Massachusetts General Hospital Biomotion Laboratory, Boston
02114-4719, USA.
Arthritis Care Res (United States) Oct 1997, 10 (5)
p308-19
OBJECTIVE: To examine in vivo maximum acetabular contact
pressures during gait and hip arthritis exercises recommended
by clinicians and the Arthritis Foundation.
METHODS: Acetabular contact pressure data were collected
for 2.5 years, at 3-4-month intervals, from an instrumented
endoprosthesis implanted in an 84-year-old male who had
sustained a left hip fracture. Maximum pressure data were
compared for each activity.
RESULTS: Mean pressures ranged from 9.0 +/- 2.3 megapascals
(MPa) during maximum isometric hip abduction, 9.0 +/- 0.8 MPa
during standing right hip abduction, and 8.9 +/- 2.8 MPa
during standing left hip abduction to 1.2 +/- 0.3 MPa during
quiet standing. Free-speed gait pressure averaged 5.6 +/- 0.9
MPa. The maximum mean pressure during side-lying hip abduction
and straight leg raise at 30 degrees/second were less than the
same activities at 60 degrees/second.
CONCLUSIONS: These in vivo hip pressure measurements
challenge traditional protocols for patients with hip
osteoarthritis and provide quantitative data as a framework
for designing exercise programs. Maximum isometric hip
exercise and standing exercise generated much higher hip
pressures, and are therefore probably more stressful to
acetabular cartilage, than gait or stationary cycling.
Clinicians must consider exercise velocity because of its
direct correlation with hip contact pressure. Walking
generated lower pressure than most activities studied and,
given its other benefits, is therefore probably beneficial for
patients with hip osteoarthritis.
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