Bioavailable testosterone in men with rheumatoid arthritis-high frequency of hypogonadism

OBJECTIVES: To study bioavailable testosterone (T) in men with rheumatoid arthritis (RA) by determining non-sex hormone-binding globulin (SHBG)-bound T (NST) under standardized conditions and to investigate if NST is related to disease variables. METHODS: Basal serum concentrations of total T, SHBG and luteinizing hormone (LH) were measured in 104 men with RA, and the levels of NST as well as the quotient T/SHBG were calculated. The data were compared with those of 99 age-matched healthy men. The results were analysed separately for the age groups 30-49, 50-59 and 60-69 yr. RESULTS: The RA men had lower NST levels than the healthy men in all age groups. T levels and the T/SHBG ratio were lower only in the age group 50-59 yr. SHBG did not differ significantly. LH was significantly lower in the patients than in the controls. Thirty-three of the 104 patients were considered to have hypogonadism compared with seven of the 99 healthy men. The only clinical variable apart from age that had a significant impact on NST was the Stanford Health Assessment Questionnaire (HAQ). CONCLUSION: Men with RA had lower levels of bioavailable T and a large proportion were considered hypogonadal. The low levels of LH suggested a central origin of the relative hypoandrogenicity.     

Long term efficacy and safety of cyclosporin versus parenteral gold in early rheumatoid arthritis: a three year study of radiographic progression,renal function,and arterial hypertension

OBJECTIVE: To compare the three year safety and efficacy of cyclosporin and parenteral gold in the treatment of early, active, severe rheumatoid arthritis (RA), and to study the reversibility of cyclosporin associated renal dysfunction in patients who discontinued cyclosporin treatment. METHODS: The patients continued to receive cyclosporin or parenteral gold in an 18 month open extension to an 18 month randomised, parallel group study. The main efficacy variable was blinded evaluation of radiographic progression of joint damage. Safety variables included serum creatinine, calculated creatinine clearance, and blood pressure. RESULTS: Radiographic progression during follow up was similar in both groups. About 60% of the patients in the intention to treat groups (n=272) and about half of the patients in the completer groups (n=114) had definite radiographic progression in joint damage (increases >6 in the Larsen-Dale score), and about one in three also had substantial progression (>18 increase in Larsen-Dale score). Both systolic and diastolic blood pressure were significantly increased in the cyclosporin group compared with the gold group, and 12/139 (9%) versus 3/139 (2%) (p=0.03) had notably raised blood pressure. The mean serum creatinine increased by 28% at the treatment end point in the cyclosporin group as compared with 7% in the gold group. The mean calculated creatinine clearance was reduced by 16% and increased by 1% in the cyclosporin and gold groups, respectively, at the end of the study. At the final follow up visit after discontinuation of cyclosporin (at least three months after treatment was stopped) the mean serum creatinine was increased by 15% and creatinine clearance reduced by 16%. Sustained increases in serum creatinine at this post-treatment end point were mostly seen in patients with a raised serum creatinine during treatment of at least 50%. CONCLUSION: Three year changes in radiographic damage during cyclosporin and parenteral gold were similar in patients with early, active RA. Abnormal renal function and raised blood pressure were often seen in the cyclosporin treated patients.     

5-Fluorouracil plus leucovorin as adjuvant treatment of an experimental liver tumor in rats

Recent experimental and clinical work has shown that leucovorin potentiates the cytotoxic effect of 5-fluorouracil (5-FU). To investigate the adjuvant role for this combination, 5-FU, 30 mg/kg, combined with leucovorin, 15 mg/kg, was administered intraperitoneally on 3 consecutive days beginning on the same day as tumor cell inoculation in the liver. Tumor take and tumor volume were registered on day 14, followed by recording of survival time. The results of the combined treatment were compared with treatment with 5-FU alone. Leucovorin in combination with 5-FU, but not 5-FU alone, significantly reduced the tumor take compared with untreated animals (p less than 0.01). The combination also resulted in smaller tumors compared with untreated animals (p less than 0.001) or with animals given 5-FU alone (p less than 0.01). The present study supports the use of leucovorin in combination with 5-FU as adjuvant treatment of patients with primary colorectal cancer.     

Substance P activates and modulates neutrophil oxidative metabolism and aggregation

The substance P (SP) fragment SP(7-11) induced chemiluminescence (CL) and aggregation in human neutrophils at high concentrations (greater than or equal to 10 microM), whereas the entire molecule SP(1-11) was less potent and the SP(1-4) fragment was inactive. At these concentrations SP and its fragments also inhibited CL and aggregation evoked by subsequent addition of formyl-methionyl-leucyl-phenylalanine (fMLP), an effect that may depend on desensitization. However, at lower concentrations (1-10 nM) SP was able to prime human neutrophils to enhanced CL and enzyme release stimulated by fMLP. These findings indicate that, in addition to direct activation of CL and aggregation, SP also modulates neutrophil function and can thus amplify the release of potentially cytotoxic substances, a possible mechanism for nervous system involvement in rheumatoid arthritis.     

Reduced bone mineral density in early rheumatoid arthritis is associated with radiological joint damage at baseline and after 2 years in women

OBJECTIVE: Data suggest that reduced bone mass may be associated with radiological damage in rheumatoid arthritis (RA). We investigated if patients with reduced bone mineral density (BMD) at onset of RA had more radiological damage at onset and after 2 years than patients with normal BMD. METHODS: BMD at lumbar spine and hip was measured in 204 patients with recent RA at presentation. At baseline and after 2 years, radiographs of hands and forefeet were evaluated according to the Larsen method. At the same time-points, Disease Activity Score (DAS 28) and functional disability (the Stanford Health Assessment Questionnaire, HAQ) were assessed. RESULTS: The 134 women and 70 men had a mean age of 55 and 61 years, respectively. Reduced bone mass (RBM, Z score < or = 1.0 SD) in at least one site was found in 46.0% of women and 62.5% of men. T and Z scores correlated significantly with Larsen scores both at baseline and after 2 years for the total patient cohort. Calculated separately for the sexes, significant correlations were found only for women. Women but not men with reduced bone mass and osteoporosis had higher Larsen scores at baseline and after 2 years than those without. From a stepwise multiple logistic regression analysis Z score trochanter and baseline C-reactive protein were selected as independent predictors of joint damage, measured as proportion over the median Larsen scores. This model could explain about 25% of the "variance" in outcome (Nagelkerke R2 = 0.27). CONCLUSION: Reduced BMD at onset of RA in women was associated with a higher Larsen score at baseline and after 2 years, indicating that the development of reduced bone mass and joint destruction in RA may have a common pathophysiological mechanism.     

Increased DHEAS levels in patients with rheumatoid arthritis after treatment with tumor necrosis factor antagonists: evidence for improved adrenal function

OBJECTIVE: To determine if major reduction of inflammation with longterm tumor necrosis factor (TNF) antagonist treatment has any influence on the adrenal and gonadal axes in patients with rheumatoid arthritis (RA). METHODS: Forty-eight patients with RA were treated with infliximab or etanercept for 2 years. Disease activity, clinical response, and physical function were evaluated and serum levels of high sensitivity C-reactive protein and interleukin 6 were analyzed before start of treatment and after 1 and 2 years. At the same timepoints adrenocorticotropic hormone (ACTH), cortisol, and dehydroepiandrosterone sulfate (DHEAS) were analyzed; luteinizing hormone (LH), estradiol, and testosterone were analyzed as well in 18 male patients. RESULTS: DHEAS increased (p 相似文献   

Fluorescence in dissolved fractions of human enamel.

Fluorescence induced by laser light is useful in early detection of enamel caries. The present work studied the fluorescence emission pattern in dissolved human enamel and in different molecular weight fractions obtained after gel chromatography or dialysis followed by ultrafiltration. For comparison, solutions of synthetic hydroxyapatite and bovine enamel were used. When the entire emission and excitation spectra of the corresponding excitation and emission wavelengths in the solutions of human enamel and bovine enamel were compared, no distinct differences were found between the solutions. With excitation at 375 nm, emission peaks were found at 460 and 560 nm, indicating the presence in human enamel solution of two different chromophores, unevenly distributed over the molecular weight fractions. The 460-nm and the lower 560-nm fluorescence peaks seem to be derived from both organic and inorganic components. The inorganic substances contributing to both the 460-nm and 560-nm peaks were incorporated in complexes. The 560-nm emission peak elucidates part of the basis of the laser fluorescence method.     

Intracranial metastases of malignant melanoma treated by surgery

Metastases in 25 patients with intracranial metastases from malignant melanoma were extirpated. Two patients had a second operation after six and ten months because of tumor recurrence. Single brain metastaσes were found in 20 and multiple in five patients. The interval between the primary tumor and the intracranial metastases varied from 17 years to six months. Three patients died due to complications from surgery. The median survival time was five months (mean survival ten months). Complete relief of symptoms was observed in 17 and partial relief in two patients. The quality of life was improved in 17 patients and 14 of these 17 went back to their ordinary occupation. The indications for neurosurgery are restricted in patients with extracranial or with multiple intracranial metastases.