Methotrexate osteopathy in long-term, low-dose methotrexate treatment for psoriasis and rheumatoid arthritis

OBJECTIVES: Herein we describe an additional case of myelolipoma of the adrenal gland, an uncommon tumor of the adrenal cortex, that had been incidentally discovered during abdominal US evaluation of the biliary tree. The clinical features, diagnosis and treatment of the condition are discussed. METHODS: Surgical treatment of the biliary tree and myelolipoma was performed through a Chevron transversal incision during the same surgical session. RESULTS: Surgery achieved good results and the postoperative course was unremarkable. CONCLUSIONS: Myelolipoma is a benign nonfunctioning tumor of the adrenal cortex comprised of adipose and hematopoietic tissue. It is usually asymptomatic and incidentally discovered during diagnostic evaluation for other pathologies. The diagnosis is made by US, CT and MRI. There is no agreement on whether surgical treatment is warranted.     

Methotrexate in the treatment of juvenile rheumatoid arthritis and other pediatric rheumatoid and nonrheumatic disorders

The goal of treatment for juvenile rheumatoid arthritis (JRA) and other pediatric rheumatic disorders is to minimize joint destruction, pain, and deformity and to maximize all aspects of growth and development. Oral and injectable methotrexate are now often given early in the treatment of JRA, childhood dermatomyositis, difficult-to-control arthritis in the pediatric spondyloarthropathies, SLE, sarcoidosis, several of the vasculopathies, and idiopathic iritis. Weekly low-dose MTX has become a mainstay of long-term improved control of these disorders, and is associated with strikingly few documented long-term side effects. Dosages, pharmacology, side effects, efficacy, and treatment strategies are discussed. Although formal studies are lacking, MTX for the pediatric rheumatic disorders seems to be associated with less frequent physician visits, lower total costs, improved function, and fewer late reconstructive surgeries.     

Cocaine disposition in saliva following intravenous, intranasal, and smoked administration

BACKGROUND: In our previous studies, chronic treatment of rats with a new beta 3-adrenoceptor agonist, CL 316,243, retarded diet-induced obesity and promoted thermogenesis in young animals and reversed established diet-induced obesity in older animals that continued to eat a high fat diet. Reversal of obesity was associated with shrinking of enlarged white adipocytes but the number of mature white adipocytes, which had not been increased by the diet, was not reduced. Drug-treatment induced appearance of abundant brown adipocytes in white adipose tissue (WAT) depots as well as hypertrophy of brown adipose tissue (BAT) in both lean and diet-induced obese rats. OBJECTIVES: To find out whether the known hyperplasia of white adipocytes in the obese fa/fa rat could be reversed by CL 316,243-treatment and whether the grossly enlarged WAT depots of the obese fa/fa rat contain precursors to brown adipocytes. RESULTS: CL 316,243 infusion (1 mg/kg/d) reduced abdominal fat. The loss of fat was due to a decrease in white adipocyte size, with no loss of the markedly elevated number of adipocytes in the fa/fa rats. Resting metabolic rate increased by 40% in lean rats, by 70% in fa/fa rats. Food intake decreased in the hyperphagic fa/fa rats but did not change in lean rats, in both lean and fa/fa rats, a marked increase in protein content of retroperitoneal WAT was associated with appearance of abundant densely-stained brown adipocytes expressing uncoupling protein (UCP) but total number of cells (from DNA content) actually decreased. Hyperinsulinemia and hyperglycemia of fa/fa rats were reduced by treatment, indicating improved sensitivity to insulin. CONCLUSIONS: Abundant precursors to brown adipocytes are present in WAT depots of fa/fa rats and much of the exaggerated increase in resting metabolic rate induced by CL 316,243 occurs in these cells. This beta 3-adrenoceptor agonist is an effective anti-obesity and anti-diabetic agent in fa/fa rats. It does not bring about disappearance of mature white adipocytes but does bring about a remodelling of WAT, with a marked change in cell composition.     

Methotrexate in juvenile rheumatoid arthritis. Evidence of age dependent pharmacokinetics

Children with juvenile rheumatoid arthritis (JRA) have been reported to require higher doses (per kg body weight) of methotrexate (MTX) than adults with rheumatoid arthritis to control their disease. The purpose of the present study was to characterise the plasma pharmacokinetics of MTX and its major metabolite, 7-hydroxymethotrexate (7-OHMTX) in children, and to compare the results with those previously obtained in adults. Thirteen patients (age 5-16 y) with JRA (median disease duration 5.5 y) were studied after once weekly oral administration of MTX (median 0.21 mg.kg-1). The analytical method was sufficiently sensitive to permit determination of plasma and urinary concentrations of MTX and 7-OHMTX during the entire dose interval in most of the patients. The dose normalized area under the plasma concentration versus time-curve (AUC) of MTX increased with the age of the children and was lower than previously found in adults. The dose normalized AUC of 7-OHMTX was not dependent on age. No correlation was found between the AUCs of MTX and 7-OHMTX. The results suggest that the age-dependence of the pharmacokinetics of MTX might explain the observation that at least some children require higher doses of MTX than adults to obtain a sufficient therapeutic effect.     

Bayesian calculation of methotrexate clearance after low dose intramuscular administration in patients with rheumatoid arthritis

OBJECTIVE: To determine a pharmacokinetic procedure (Bayesian method) for estimation of methotrexate (MTX) clearance, using only 2 blood samples, in outpatients with rheumatoid arthritis treated with low dose intramuscular (i.m.) MTX. METHODS: Population pharmacokinetic parameters were obtained by the weighted least squares (WLSQ) method in plasma samples from 14 patients with rheumatoid arthritis (RA). In each patient, 11 samples were measured by fluorescence polarization immunoassay, at Time 0, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 12, and 24 h after i.m. administration. These measures were validated by pharmacokinetic studies in 20 other patients with RA. Individual total body clearance of MTX was calculated using only 2 plasma samples (at 0.5 and 2 h after i.m. injection) by the Bayesian method using the population pharmacokinetic parameters. The clearance measures obtained by the Bayesian method were compared with those obtained by the WLSQ method. RESULTS: The pharmacokinetic variables (clearance, half-life, area under the curve) of 14 patients were determined, as well as the covariance and the mean values necessary to apply the Bayesian method. No significant difference was found between clearance values obtained by the Bayesian method compared to the WLSQ method, confirming the validity of the Bayesian values. CONCLUSION: The present population pharmacokinetic parameters allowed the determination of individual clearance of MTX with only 2 plasma samples (0.5 and 2 h after administration) in patients treated with low dose im MTX. Individual clearance is used to modulate MTX administration in patients presenting adverse reactions in spite of good clinical response. Individual determination of MTX pharmacokinetics in patients at risk for adverse MTX reactions could be useful for adjustment of the drug regimen.     

HLA-DM polymorphisms in patients with rheumatoid arthritis

OBJECTIVE: To investigate the contribution of HLA-DMA and DMB genes, which play a crucial role in the HLA class II restricted antigen presentation pathway, in susceptibility to rheumatoid arthritis (RA). METHODS: The distribution of DMA and DMB alleles was examined in patients with RA and in healthy subjects by oligotyping of PCR amplified genomic DNA with sequence specific oligonucleotide probes. RESULTS: There were no significant differences in the prevalence of DMA and DMB alleles in patients with RA as compared to healthy controls. In addition, no significant differences in frequencies of DMA and DMB alleles were observed in RA susceptibility epitope positive RA patients and controls. CONCLUSION: DMA and DMB genes do not appear to play a role in susceptibility to RA.     

Chloroquine retinopathy in patients with rheumatoid arthritis

The paper presents data on the differential fertility of schizophrenics and controls, and the fertility of their siblings. This study used several methodological procedures in the study of schizophrenia reproduction, which strengthens the validity of the findings. Firstly, both male and female rates were examined. Secondly, the method of selection of a control avoided the biases introduced by using census data or other non-matched controls. Third, a diagnostic criterion was used which minimizes the possibility of the inclusion of other psychiatric illnesses. The results obtained support prior reports of the lowered reproductive rates of schizophrenics. Further, the siblings of schizophrenics were found not to have a reproductive advantage when contrasted to control siblings. The failure to find a reproductive advantage conflicts with a hypothesis of a balanced polymorphism as the mechanism maintaining an apparent constant rate of schizophrenia.     

Ankle arthrodesis in patients with rheumatoid arthritis

The results of 26 ankle arthrodeses performed for rheumatoid arthritis on 21 patients were reviewed. Tibiotalar arthrodesis was performed in 14 ankles, and tibiotalocalcaneal arthrodesis was performed in 12. External fixation was used in 20 ankles, and internal fixation was used in six. Followup was available in 24 of 26 ankles (19 patients), and averaged 5 years (range, 2-8 years). There was no pain experienced in 19 ankles; mild, occasional pain was experienced in four ankles; and moderate, daily pain was experienced in one ankle. Daily activities were limited in five patients and recreational activities were limited in 11. All patients reported some difficulty walking on uneven terrain. Nearly all patients were satisfied; two were satisfied with reservations and two were dissatisfied. Union was achieved in 25 of 26 (96%) ankles. Ankle arthrodesis is an effective operation in patients with rheumatoid arthritis. Unlike previous reports, union and complication rates in this series were comparable with rates for arthrodesis for posttraumatic and degenerative arthritis.     

Lymphocyte depletion in patients with rheumatoid arthritis

Sixteen patients with severe rheumatoid arthritis, marked inflammation of the synonvial membrane and high rheumatoid titer were cannulated by the thoracic duct for a period rangin between 82 up to 100 days. The patients being not under any medication during that time. Quantitative and qualitative analysis of the lymphocytes were performed, as well as responses to mitogens, rheumatoid factor, circulating antibodies and delayed hypersensitivity. By the 14th day nearly all the patients had a partial or almost complete remission of their disease. No complications were observed. These results will be discussed.     

Methotrexate therapy in rheumatoid arthritis: a life table review of 587 patients treated in community practice

To determine whether methotrexate (MTX) maintains its effectiveness in rheumatoid arthritis (RA) in the setting of community based private rheumatology practice we used life table analysis to review the combined experience of a group of these practices. Of 587 patients with RA who started to take MTX, total termination rate at 70 months was 24.4% with most terminations prompted by drug toxicity. Older age (greater than 65 years) was associated with higher rates of toxicity. Treatment termination rates varied substantially between rheumatologists. We conclude that MTX therapy for RA is well tolerated and maintains effectiveness for at least 70 months.     

Prevalence and depression degree in patients with rheumatoid arthritis

BACKGROUND: Study goals were: a) to know the existence and depressive level among a series of rheumatoid arthritis (RA) patients; b) to assess differences in depression levels of individuals with and without RA, and c) to identify the association of depression level with socioepidemiological, clinical, and prognostic characteristics in these patients. MATERIAL AND METHODS: Cross-sectional study that undertakes a 3 years period (July 1992-March 1995) and includes 221 patients diagnosed of RA according to the 1988 criteria of the American College of Rheumatology (ACR). Association of depression levels, assessed with the Self-Rating Depression Scale of Zung-Conde, with each one of the variables was evaluated using chi 2 tests (p < 0.05). A multivariate analysis type Automatic Interaction Detection (AID), based on the statistic r2, was applied to determine patient's profile with RA and depression. RESULTS: Depressive level was identified in 33.48% of patients. Odds ratio (OR) between "not depressive" and "depressive" levels was from 20.35 with 95% CI: 8.87-47.88 (p < 0.00001). Association was found with the variables sex (p < 0.0001), profession (p = 0.02), weight and height (p < 0.0001 in both variables), Ritchie index (p < 0.004), number of painful joints (p = 0.002), morning stiffness (p = 0.049) and secondary effects of the treatment (p = 0.034). Sex was the variable that most influenced in depressive level (p < 0.00001). In females group, the factor mainly related with depression was the number of painful joints (p < 0.0002) while in males, it was the self-rating pain valuation with a Likert scale (p < 0.0001). CONCLUSIONS: RA could causes depression in the patients. The factor with highest influence in the depression of these patients was the sex. The most influential factor in the females was the number of painful joints, while in the males was the self-rating of pain.     

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

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

Cementless hip prosthesis in patients with rheumatoid arthritis

A recent study conducted in Sweden reported that 1) leukemia risk in children who lived near 220 or 400 kV electric-power transmission lines was associated with calculated historical magnetic field levels; 2) children living within a distance of 50 m of transmission lines had an elevated risk of leukemia; and 3) there was no association between leukemia and residential magnetic fields measured many years after diagnosis. Subsequently, these investigators found through logistic regression analysis that disease was more strongly associated with calculated historical fields than with distance. Since the calculated historical fields in that study depended predominantly on distance and transmission-line load current, the logistic regression results suggest that historical load current plays an important role in the epidemiological results. Thus, we studied hourly 1974 load-current data for six transmission lines, and we examined 1958-1985 annual load-current data for 112 transmission lines. Most lines exhibited marked diurnal load-current rhythms during 1974, and all six showed systematic weekday-weekend differences. During 1958-1985, average loadings of Swedish 220 and 400 kV lines increased by about 1.3% year. Predictive-value and kappa-statistic analyses indicated that Swedish transmission-line load currents were not stable over long periods, so that contemporaneous load current (or a contemporary magnetic field measurement) was not a good surrogate for historical load current (or historical magnetic fields). The results provide a potential explanation of the failure of the Swedish Study to find an association between leukemia and contemporaneous magnetic field levels measured many years after the etiologic period, and suggest that the inclusion of load-current data could significantly improve the quality of historical field calculations.     

Endogenous opioid tone in patients with rheumatoid arthritis

A monoclonal antibody giving a dominant reaction with the group-specific polysaccharide of streptococcus group B in an ELISA test has been developed. The purified polysaccharide exhibited a high positivity with reference anti B streptococcal antiserum in the ELISA test. Cross-tests of antibodies with other groups of streptococci provided a minimum cross-reaction only in the case of G streptococci. Monoclonal antibodies were prepared using Streptococcus agalactiae S 589 MT strain isolated from a case of bovine mastitis which does not express Ia, Ib, II, III, IV and V type antigens, nor C, R and X protein antigens.