The use of methotrexate in rheumatoid arthritis

OBJECTIVE: To address the long-term efficacy and toxicity issues related to methotrexate (MTX) and compare it with other disease-modifying antirheumatic drugs (DMARDs). METHODS: Review of the international literature on the clinical use of MTX in rheumatoid arthritis (RA) disease. RESULTS: MTX has emerged as a relatively safe and effective treatment for RA that compares favorably with other therapies, particularly because of its considerably longer median drug survival. The toxicity profile of MTX is well established and includes serious and sometimes fatal liver disease, pneumonitis, and cytopenias. Hence, regular and careful monitoring of patients taking MTX is essential, particularly when MTX is combined with other DMARDs. Folate supplementation can reduce some of the most common side effects of MTX, but it has not yet been established whether this translates into a reduced risk of serious disease. Another potential approach to reducing the toxicity of MTX is therapeutic drug monitoring and dose individualization. However, correlations between pharmacokinetics and clinical response have been addressed in only a few studies and with conflicting results. CONCLUSIONS: MTX is an effective DMARD with a relatively safe profile compared with other therapies. Folate supplementation can significantly reduce the risk of MTX toxicity. Finally, it is essential that patients be monitored carefully to reduce the potential serious toxicities of MTX.     

Non-hormonal therapy of post-menopausal vasomotor symptoms: a structured evidence-based review

Background Interest in non-hormonal therapies for the treatment of menopausal symptoms has increased since the publication of adverse effects of estrogen replacement therapy. Objective To provide information on the efficacy of non-hormonal therapies for menopausal vasomotor symptoms based on evidence from published randomised controlled studies. Methods The Cochrane Database of Systematic Reviews (CDSR), MEDLINE, Alternative Therapies in Health and Medicine database (ATHMD) and Allied and Complementary Medicine database (AMED) were searched for randomised controlled trials in the English language reporting data on treatment of menopausal vasomotor symptoms. Trials including cancer breast patients were included. Results Our search identified 58 randomised controlled trials of which 11 involved the use of clonidine, six for SSRIs, four for gabapentin, seven for black cohosh, seven for red clover, 18 for phytoestrogens, two for ginseng, one for evening primrose, one for dong quai and one for vitamin E. Most trials had methodological deficiencies. Conclusion There is evidence that clonidine, paroxetine, venlafaxine, gabapentin and black cohosh may be beneficial in the treatment of menopausal vasomotor symptoms in some women. Current evidence does not support the use of fluoxetine, red clover, phytoestrogens, Ginseng, evening primrose, dong quai and vitamin E. The side effects profile of these therapies should be considered.     

Molecular evidence for the presence of chlamydia in the synovium of patients with reiter's syndrome

Objective. There is much evidence indicating that chlamydial antigens in the synovium may be critical in the pathogenesis of Reiter's syndrome (RS), but it is not known whether intact organisms are present in that tissue in any stage of the disease. The present study was undertaken to begin to address this question. Methods. We used a highly specific and sensitive molecular hybridization screening system which detects chlamydial RNA, to examine synovial biopsy samples from 22 patients with various arthropathies, including 9 with RS. Results. Seven of the 9 RS patients were positive for chlamydial RNA, while 3 of the 13 non-RS patients were also positive; positive results in the non-RS patients probably indicate the actual presence of the organism, since these patients had arthritis that was otherwise incompletely explained. Conclusion. The detection of chlamydial RNA, in combination with previous findings of chlamydia-like particles and/or chlamydial antigens in the synovium of RS patients, suggests that whole bacterial cells are present in that tissue.     

Release in vitro of adipsin, vascular cell adhesion molecule 1, angiotensin 1-converting enzyme, and soluble tumor necrosis factor receptor 2 by human omental adipose tissue as well as by the nonfat cells and adipocytes

The relative release in vitro of adipsin, vascular cell adhesion molecule (VCAM) 1, angiotensin 1-converting enzyme (ACE), and soluble tumor necrosis factor alpha receptor 2 (sTNFR2) by explants of human omental and subcutaneous adipose tissue as well as the nonfat cell fractions and adipocytes from morbidly obese gastric bypass women was compared with that by tissue from obese abdominoplasty patients. Release of VCAM-1 and ACE by omental adipose tissue explants was 220% and 80% greater, respectively, over 48 hours of incubation than that by subcutaneous adipose tissue explants. However, this difference was not seen when release by adipocytes derived from omental fat was compared with that by adipocytes from subcutaneous fat. The release of adipsin and sTNFR2 by omental adipose tissue explants did not differ from that by subcutaneous tissue adipose tissue. The release of adipsin by tissue explants over 48 hours was 100-fold greater than that of VCAM-1, ACE, or sTNFR2. Most of the release of all 4 adipokines was due to the nonfat cells because adipsin release by adipocytes was only 13% of that by the nonfat cells derived from the same amount of adipose tissue, whereas ACE release by adipocytes was 7% and release of VCAM-1 as well as sTNFR2 by adipocytes was 4% or less of that by nonfat cells. The total release in vitro of ACE and sTNFR2, but not that of adipsin or VCAM-1, was enhanced in adipose tissue explants from morbidly obese women as compared with those by explants derived from obese women. We conclude that although human adipose tissue explants release appreciable amounts of adipsin and far smaller amounts of VCAM-1, ACE, and sTNFR2 in vitro, more than 87% of the release is due to the nonfat cells present in adipose tissue. Furthermore, the enhanced release of VCAM-1 and ACE seen in omental adipose tissue explants as compared with explants of subcutaneous adipose tissue is due to release by nonfat cells.     

Robot-assisted catheter manipulation for intracardiac navigation

Objective  Manual navigation of intracardiac steerable catheters is inaccurate, requires dexterity for efficient manipulation of the catheter, and exposes the interventionalist to ionizing radiation. The objective of this research is to develop a system that replaces the interventionalists’s hands in catheter manipulation for accurate and semi-automatic tele-navigation of catheters. Methods  Based on a proposed kinematic model for the distal shaft of the catheter, a system has been developed for assisted navigation of intracardiac catheters. When the distal shaft of the catheter lies inside a cardiac chamber, a robotic apparatus is utilized for automatic steering of the catheter tip to reach designated targets within the chamber. Results  The catheter modeling was validated through the experiments on three swine. The robotic system could navigate the catheter tip to designated targets with a mean distance of 6.53 mm from the target. Conclusion  Preliminary in vivo studies demonstrate the feasible application of the system in catheter navigation and the validity of catheter modeling and control strategies.     

Transverse dislocation of the elbow with ipsilateral shaft of radius fracture in an adult

Study design  

A report of a rare case of transverse dislocation of the elbow associated with fracture of the shaft of the ipsilateral radius.     

Mineral balance and whole body bone mineral content in very low-birth-weight infants

Fat and mineral metabolic balance studies were performed in 25 normal very low-birth-weight infants ( 1500 g at birth) fed either pooled pasteurized human milk supplemented with calcium, phosphorus and magnesium, or a preterm formula. Calcium, phosphorus and magnesium intake were similar in both groups and averaged 100mg/kg/day, 72 mg/kg/day and 8 mg/kg/day, respectively. Calcium and phosphorus retention was higher in the subjects fed fortified human milk than in those receiving a preterm formula (65±14 and 62±9mg/kg/day versus 55±12 and 47±7mg/kg/day respectively). The difference was only significant for phosphorus. Magnesium retention was similar in the two groups and averaged 3 mg/kg/day. Fat intake and absorption was significantly higher in the preterm formula fed group than in the one fed fortified human milk (5.5±0.4 g/kg/day and 88±4% versus 4.2±1 g/kg/day, 79±6% respectively). Assessment of the whole body bone mineral content by dual energy X-ray absorptiometry was performed at 3 and 6 months of age in another group of 25 low-birth-weight infants fed either fortified human milk or a preterm formula. Whole body bone mineral content (BMCt) was low (43.3±30.8 g of hydroxyapatite) at 3 months of age (theoretical term) compared to normal full-term newborns at birth. There was no significant influence of the diet. At 6 months of age, BMCt reached 168.6±36.6g, a value similar to that of full-term newborns, with no significant difference between the two regimen groups. The deficit in the 12 subjects who had a BMCt under 30 g at 3 months of age had been corrected at age 6 months. Premature babies fed a pooled pasteurized human milk enriched with calcium, phosphorus and magnesium favored a better retention of calcium and phosphorus. However, no significant influence of the two diets studied was observed on the gain in BMCt over the first 6 months of life.     

Simultaneous measurement of gallbladder emptying with cholescintigraphy and US during infusion of physiologic doses of cholecystokinin: a comparison

Both ultrasonography (US) and cholescintigraphy are used to study gallbladder dynamics. The present study was undertaken to determine whether the two methods provide the same or different information relating to gallbladder emptying. Emptying was simultaneously studied with both methods during infusion of graded physiologic doses of cholecystokinin (CCK) in six healthy subjects. Infusion of stepwise increasing doses of CCK, ranging from 0.03 to 0.5 Ivy dog units per kilogram of body weight per hour (IDU/kg.h), induced significant dose-related increases in plasma CCK, decreases in gallbladder volume assessed with US, and gallbladder emptying assessed with cholescintigraphy. The threshold dose for inducing significant gallbladder emptying was 0.13 IDU/kg.h, as determined with both techniques, indicating similar detection limits. There was a highly significant correlation between decreases in gallbladder volume and decreases in radioactive counts over the gallbladder region, with a tendency toward greater gallbladder responses at sonography during the early phase of gallbladder contraction and toward greater responses at cholescintigraphy during the later phase of gallbladder contraction. It is concluded that these methods can be used interchangeably for the quantitation of gallbladder emptying.