Combination second-line therapy for rheumatoid arthritis.
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Arthritis, Rheumatoid↗
Biomedical subjects
H J Williams
Publications and source records attributed to H J Williams.
Healing of broken human chromosomes by the addition of telomeric repeats.
We have characterized and compared a series of naturally occurring chromosomal truncations involving the terminal region of the short arm of human chromosome 16 (16p13.3). All six broken chromosomes appear to have been stabilized by the direct addition of telomeric repeats (TTAGGG)n to nontelomeric DNA. In five of the six chromosomes, sequence analysis shows that the three of four nucleotides preceding the point of telomere addition are complementary to and in phase with the putative RNA template of human telomerase. Otherwise we have found no common structural features around the breakpoint regions. These findings, together with previously reported in vitro data, suggest that chromosome-healing events in man can be mediated by telomerase and that a small region of complementarity to the RNA template of telomerase at the end of a broken chromosome may be sufficient to prime healing in vivo.
Base Sequence↗
Comparison of hydroxychloroquine and placebo in the treatment of the arthropathy of mild systemic lupus erythematosus.
OBJECTIVE: To compare the relative safety and efficacy of hydroxychloroquine (HCQ) and placebo (Pl) in the treatment of the articular complaints of systemic lupus erythematosus (SLE). METHODS: Seventy-one patients with mild SLE requiring < or = 10 mg of prednisone or equivalent daily and with arthritis or arthralgias were entered into a 48-week prospective, controlled, double blind multicenter trial and randomly assigned to either HCQ or Pl. RESULTS: Both HCQ and Pl were well tolerated in the 48-week trial. There were no remissions. With the exception of the patient assessment of joint pain, all other joint measures were similar between the groups. Twenty-nine patients withdrew before the end of the trial although only 2 patients withdrew for adverse drug effects. CONCLUSION: Our study found subjective pain relief as the only statistically significant difference in joint count variables from HCQ in the treatment of the articular manifestations of SLE.
Adult↗
Factitious simulation of systemic lupus erythematosus.
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Adult↗
Early undifferentiated connective tissue disease: III. Outcome and prognostic indicators in early scleroderma (systemic sclerosis).
OBJECTIVE: To characterize the course of early scleroderma and to delineate prognostic factors present within 1 year of disease onset that might identify patients at high risk. DESIGN: Inception cohort study. SETTING: Ten university-based rheumatology clinics participating in the Cooperative Systematic Studies of Rheumatic Diseases Program. PATIENTS: Forty-eight patients who had had scleroderma for less than 1 year. MEASUREMENTS: Fifteen patients with early scleroderma who died were compared with those still living during the initial study period (1982 to 1992). Kaplan-Meier survival estimation and Cox proportional hazards analysis were used to analyze baseline variables for their ability to predict survival duration. RESULTS: Eight of 15 deaths were due to cardiac or pulmonary system failure. The estimated 5-year survival rate was 68%. Baseline factors that were the most predictive of a poor outcome included the presence of abnormal cardiopulmonary signs and abnormal urine sediment (pyuria, hematuria). CONCLUSION: Evidence of early cardiopulmonary disease, renal disease, inflammation, or immune activation may identify a subset of patients with scleroderma who will experience rapidly progressive disease and early death.
Adult↗
Comparison of naproxen and acetaminophen in a two-year study of treatment of osteoarthritis of the knee.
OBJECTIVE: To compare the relative safety and efficacy of naproxen and acetaminophen in the treatment of osteoarthritis (OA) of the knee. The major outcome measures were radiographic progression and withdrawal from the trial due to lack of efficacy. METHODS: One hundred seventy-eight patients with OA of the knee were enrolled in a 2-year prospective, controlled, double-blind multicenter trial and were randomly assigned to receive acetaminophen (ACT) or naproxen (NPX) treatment. RESULTS: After 6 weeks of treatment, modest improvement in pain on motion and in physician's global assessment was seen in both the ACT and the NPX groups, and the NPX group also had modest improvement in pain at rest and in 50-foot walk time. Sixty-two patients completed the 2-year study. Among these patients, radiographic progression was similar in the 2 treatment groups. Withdrawal from the trial due to lack of drug efficacy was slightly more frequent among patients in the ACT group (22% versus 16%), but withdrawal due to adverse drug effects was slightly more common in the NPX group (23% versus 18%). CONCLUSION: The efficacy of ACT treatment and NPX treatment was similar, although it was slightly better for NPX. The toxicity rate was slightly lower with ACT. However, the high rate of withdrawal in both treatment groups suggests that neither is satisfactory for the treatment of OA.
Acetaminophen↗
Interaction of 2,3,7,8-tetrachlorodibenzo-p-dioxin, 12-O-tetradecanoylphorbol-13-acetate (TPA) and 17 beta-estradiol in MCF-7 human breast cancer cells.
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and 12-O-tetradecanoylphorbol-13-acetate (TPA) are both tumor promoters which act through different mechanisms. In MCF-7 human breast cancer cells, both TCDD and TPA inhibited constitutive and 17 beta-estradiol-induced cell proliferation but showed no apparent interactive effects. TCDD also inhibited the 17 beta-estradiol-induced secretion of the 52-kDa protein (procathepsin D) and induced CYP1A1 gene expression whereas TPA alone was inactive for these responses. Moreover, TPA did not modulate the TCDD-mediated antiestrogenic or induction responses and did not decrease levels of the nuclear Ah receptor complex as determined in a gel mobility shift assay using a 32P-dioxin responsive element (DRE). The interactions of TPA and TCDD on the metabolism of [13C]glucose to [13C]lactate was also investigated using 13C-nuclear magnetic resonance spectroscopy. The rate of formation of [13C]lactate from [13C]glucose in MCF-7 cells treated with DMSO (control), 1 nM 17 beta-estradiol, 1 nM TCDD, 1 nM TCDD plus 1 nM 17 beta-estradiol, and 0.1 ng/ml TPA plus 1 nM 17 beta-estradiol was 28, 48, 20, 22 and 50 fmol lactate formed/cell/h, respectively. Thus, TCDD, but not TPA, inhibited this estrogen-induced response. However, a comparison of the rate of lactate formation in cells treated with TCDD plus 17 beta-estradiol (22 fmol/cell/h) or TCDD plus 17 beta-estradiol plus TPA (61 fmol/cell/h) showed that TPA significantly inhibited the TCDD-mediated antiestrogenic response. The results of these studies in MCF-7 cells demonstrate that the interactions of TCDD and TPA are highly response-specific and do not involve TPA-mediated downregulation of the nuclear Ah receptor complex.
Base Sequence↗
New sesquiterpene alpha-methylene lactones from the Egyptian plant Jasonia candicans.
Extracts of the plant Jasonia candicans possess antimicrobial activity. ET2O/MeOH extracts were subjected to liquid chromatography, and several sesquiterpenes were isolated and identified including the known compounds confertin [1], 4,11(13)-eudesmadien-12-oic acid [2], and 11-eudesmen-4-ol [3]. Two new diol alpha-methylene lactone antimicrobial agents were identified from nmr and mass spectral data and X-ray crystallography as (4 alpha, 5 alpha, 8 beta, 10 beta)-4,10-dihydroxy-1,11(13)-guaidien-12,8-olide [4] and (4 alpha, 5 alpha, 8 beta, 10 alpha)-4,10-dihydroxyl-1,11 (13)-guaidien-12,8-olide[5], which differ in stereochemistry at the C-10 tertiary alcohol center.
Lactones↗
Clinical trials in rheumatology.
The randomized controlled trial continues to be the standard for evaluating the clinical utility of new procedures or treatments. The randomized controlled trial seems to affect the clinical practice of physicians. Although the design of the randomized controlled trial is well described, consideration should be given to the questions asked and whether the trial is conducted and analyzed so that the questions can be answered. Comparative trials have become more frequent than placebo trials in the past decade, and clinical research financing is falling increasingly to the pharmaceutical industry. Process and outcome measures are receiving more attention. Various groups and committees are evaluating disease activity measures to delineate a small number that can become core or foundation measures. These measures are also being defined and standardized. The process is much further advanced for rheumatoid arthritis than for other diseases, and some common and perhaps "mundane" disease states are being neglected.
Arthritis, Rheumatoid↗
Comparison of auranofin, methotrexate, and the combination of both in the treatment of rheumatoid arthritis. A controlled clinical trial.
OBJECTIVE: To compare the relative safety and efficacy of auranofin (AUR), methotrexate (MTX), and the combination of both in the treatment of active rheumatoid arthritis (RA). METHODS: Three hundred thirty-five patients with active RA were entered into a 48-week, prospective, controlled, double-blind, multicenter trial and were randomly assigned to 1 of 3 treatment groups. RESULTS: Two hundred eleven patients completed the trial. No remissions were seen, and there were no statistically significant differences among the treatment groups in the clinical or laboratory variables measured. Patients taking AUR alone had a slower onset of response than did patients taking MTX alone or in combination. Withdrawals because of adverse drug reactions were slightly more common for those taking combination therapy, but the differences were not statistically significant. Withdrawals because of lack of response were more common for single-drug therapy, with the difference between AUR and the combination reaching statistical significance. No unexpected adverse drug effects were identified, and all reactions resolved without sequelae. CONCLUSION: Except for fewer withdrawals because of lack of response, combination therapy did not demonstrate any advantage in efficacy over single-drug treatment within the time frame of the study.
Adolescent↗
Primary radiologic realignment of membranous urethral disruptions.
A forty-two-year-old man with a traumatic, membranous urethral disruption underwent initial suprapubic catheter urinary diversion followed by a primary realignment twenty-one days after injury. Realignment was accomplished radiologically using an anterograde guide wire engaged by a retrograde stone basket and subsequent Foley catheter placement over the wire. The patient has remained totally continent, having partial erections, two years after injury, with no further intervention.
Adult↗
Purification of an indole alkaloid biosynthetic enzyme, strictosidine synthase, from a recombinant strain of Escherichia coli.
The gene for the indole alkaloid biosynthetic enzyme, strictosidine synthase, of Catharanthus roseus has been cloned into an inducible Escherichia coli expression vector using an expression cassette polymerase chain reaction technique. Induction of the gene resulted in overexpression of the enzyme which accumulated mainly as insoluble inclusion bodies. Denaturation and refolding of the insoluble protein resulted in the ability to purify up to 6 mg of active enzyme from a single liter of cell culture. The recombinant enzyme has good activity (approximately 30 nkat/mg).
Alkaloids↗
Isolation and identification of xochitloldione and isoxochitlolone from Cnidosculus urens.
Major components of MeOH extracts from the plant roots of Cnidosculus urens purified by cc and tlc and crystallization were lupeol acetate and the previously unreported compounds isoxochitlolone [1] and xochitloldione [2], which were identified through mass, ir, nmr, and uv spectroscopy and X-ray crystallography. In preliminary testing, isoxochitlolone has been found to be active against Escherichia coli and Staphylococcus aureus.
Anti-Bacterial Agents↗
Analysis of failure after curative irradiation of extrahepatic bile duct carcinoma.
Thirty-four patients with subtotally resected or unresectable carcinoma of the extrahepatic bile ducts received radiation therapy; a minimum of 45 Gy (external beam) to the tumor and regional lymph nodes +/- 5-fluorouracil (5-FU). Seventeen patients received an external beam boost of 5 to 15 Gy to the tumor, and a specialized boost was used in the remaining 17 patients (iridium-192 transcatheter seeds in 10 and intraoperative radiation therapy [IORT] with electrons in seven). The median time to death in all 34 patients was 12 months (range, 4 to 98-months). The only patients who survived longer than 18 months were those either with gross total or subtotal resection before external irradiation (2 of 6) or who received specialized boosts (192Ir, 3 of 10; IORT, 3 of 7). Local failure was documented in 9 of 17 patients who received external beam irradiation alone +/- 5-FU, 3 of 10 patients who received an 192Ir boost, and 2 of 6 patients who received an IORT boost with curative intent.
Adenoma, Bile Duct↗
Eating attitudes in survivors of unwanted sexual experiences.
To investigate an hypothesized link between unwanted sexual experiences in childhood and later problems with eating, 21 survivors of sexual abuse completed three questionnaires: the Eating Attitudes Test, the Sexual Events Questionnaire, and the General Health Questionnaire. These women scored high on the EAT, and scores were higher for women who reported more sexual experiences. A similar relation was found between number of sexual experiences and depression, and anxiety and insomnia, but not with somatic symptoms. The implications of these findings for intervention in sexual abuse and eating disorder cases are discussed.
Adolescent↗
Current method of management of rheumatoid arthritis.
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Arthritis, Rheumatoid↗
Isolated calcaneal metastasis in a patient with endometrial adenocarcinoma.
A 55-year-old woman with a history of Stage IA endometrial adenocarcinoma, previously treated with surgery and intracavitary radiation therapy, had an isolated calcaneal metastasis. Normal radiographs led to a delay in the diagnosis of her relapse. An ankle computed tomographic scan finally identified a mass, and the surgical biopsy specimen confirmed the diagnosis. This is the first reported case of an isolated calcaneal metastasis in endometrial adenocarcinoma to the authors' knowledge.
Adenocarcinoma↗