Biomarkers of inflammation in patients with unclassified polyarthritis and early rheumatoid arthritis. Relationship to disease activity and radiographic outcome

OBJECTIVE: To determine plasma interleukin 6 (pIL-6), plasma vascular endothelial growth factor (pVEGF), and serum (s) YKL-40 in patients with early rheumatoid arthritis (RA) and unclassified polyarthritis (PA), and investigate their relationship with radiographic outcome. METHODS: pIL-6 and pVEGF were determined by ELISA and sYKL-40 by an in-house radioimmunoassay in 51 patients with early RA and 21 with PA. Patients were followed with clinical and biochemical measurement every month for 2 years. Conventional radiographs of hands, wrists, and forefeet were scored according to the Larsen method, and magnetic resonance imaging of 2nd to 5th metacarpophalangeal joints of the dominant hand were evaluated for presence or absence of bone erosions. RESULTS: Baseline pIL-6, pVEGF, sYKL-40, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) were elevated in RA patients compared to healthy persons (p < 0.001), but were not in patients with PA. Patients with early RA had higher pIL-6 (p = 0.007), pVEGF (p = 0.02), and sYKL-40 (p = 0.024) compared to PA patients. pIL-6, sYKL-40, CRP, and ESR but not pVEGF decreased in patients that responded to treatment after 2 years. The mean value of pIL-6 during the first and second year were higher in patients with early RA with progression in bone erosions (n = 14) compared to early RA patients without progression (n = 30; first year 8.4 vs 2.8 ng/l, p = 0.04; second year 6.1 vs 3.6 ng/l, p = 0.03). CONCLUSION:Plasma IL-6 was the only biomarker related to treatment response and progressive erosive disease in patients with early RA, but it may not give additional information compared to CRP in relation to disease activity and treatment response.     

A guinea pig strain with recessive heredity of deafness, producing normal-hearing heterozygotes with resistance to noise trauma

A new strain of waltzing guinea pigs arose spontaneously in a guinea pig breeding facility in Germany in 1996. In addition to obvious vestibular dysfunction, the waltzing animals appear deaf already at birth. Histological analysis revealed that the waltzers lack an open scala media due to the collapse of Reissner's membrane onto the surface of the hearing organ. Subsequent breeding has shown that this strain has a recessive mode of inheritance. The homozygotes are deaf and display a waltzing behaviour throughout their lives while the heterozygotes show no significant signs of inner ear injury despite being carriers of this specific mutated gene of hearing impairment. However, the heterozygous animals offer the opportunity to study how hereditary factors interact with auditory stress. In the present study, the susceptibility of the carriers to noise was investigated. Auditory brainstem responses were obtained prior to and after noise exposure (4 kHz, 110 dB, 6 h). The carriers were significantly less affected by the noise as compared to control animals. This difference was still significant at 4 weeks following noise exposure. It is suggested that the heterozygous animals have an endogenous resistance to auditory stress.     

Ovarian ultrasound and ovarian and adrenal hormones before and after treatment for hyperthyroidism

OBJECTIVE: To relate thyroid, steroid and pituitary hormones to ovarian ultrasonographic findings in hyperthyroid patients before and during treatment. STUDY DESIGN: Ultrasonography of the ovaries and serum hormone determination by immunoassay were performed before and during thiamazole therapy in 18 women of fertile age treated for hyperthyroidism at the Danderyd Hospital from 1996 to 1998. RESULTS: When hyperthyreotic, the patients had elevated serum levels of sex hormone-binding globulin (SHBG) and subnormal values of cortisol, free testosterone (fT) and dehydroepiandrosterone (DHEA). In the euthyreotic state following treatment, endocrine variables were normalized. Patients with a short duration of the disease had higher pretreatment levels of free thyroxine (fT4), SHBG and testosterone and lower corticosteroid binding globulin (CBG) and cortisol levels compared to patients with a long duration of the disease. The pretreatment ultrasonographic picture was abnormal in 16 of 18 patients. Of the 8 patients who were examined by ultrasonography after 3 months of treatment, all but 1 showed a normal picture. Samples from patients showing an abnormal ultrasonographic picture had significantly higher fT4 and lower free testosterone (fT) values than samples from patients with a normal ultrasonographic picture. CONCLUSION: Ultrasonographic findings showing a multicystic/multifollicular picture, resembling polycystic ovaries (PCO), in hyperthyroidism may be related to direct effects of thyroid hormones on the ovaries and/or altered intraovarian androgen environment due to elevated SHBG levels. It is highly recommended to assess the thyroid status in patients with multicystic/multifollicular ovaries/PCO.     

Residence near power lines and the risk of birth defects

BACKGROUND: There has been some concern that exposure to electromagnetic fields may cause birth defects. We studied risks of birth defects by residential exposure to 50-Hz magnetic fields from power lines. METHODS: We estimated the distance between residence and power lines for 161,844 Norwegian residences, and their corresponding magnetic fields in the period 1980 to 1997. Risks of 24 categories of birth defects were compared across exposure levels, adjusting for social and demographic variables. RESULTS: Among those living near power lines, the greatest reductions in risk were for cardiac defects (odds ratio = 0.5; 95% confidence interval = 0.3-0.9) and respiratory defects (0.4; 0.2-0.9). The largest increase in risk was for esophageal defects (2.5; 1.0-5.9). Other associations were weaker and had wide confidence intervals. CONCLUSIONS: There was little evidence that residence near power lines affected the risk of birth defects. The observed decreased risks of cardiac and respiratory defects and the increased risk of esophageal defects should be interpreted with caution given the number of endpoints, the imprecision in the calculations of the distance from the residence to the power line, and the limited information on pregnant women's change of residence.     

Evaluation of different types of alginate microcapsules as bioreactors for producing endostatin

The use of nonautologous cell lines producing a therapeutic substance encapsulated within alginate microcapsules could be an alternative way of treating different diseases in a cost-effective way. Malignant brain tumors have been proposed to be treated locally using engineered cells secreting proteins with therapeutic potential encapsulated within alginate microcapsules. Optimization of the alginate capsule bioreactors is needed before this treatment can be a reality. Recently, we have demonstrated that alginate-poly-L-lysine microcapsules made with high-G alginate and a gelled core disintegrated as cells proliferated. In this study we examined the growth and endostatin secretion of 293-EBNA (293 endo) cells encapsulated in six different alginate microcapsules made with native high-G alginate or enzymatically tailored alginate. Stability studies using an osmotic pressure test showed that alginate-poly-L-lysine-alginate microcapsules made with enzymatically tailored alginate was mechanically stronger than alginate capsules made with native high-G alginate. Growth studies showed that the proliferation of 293 endo cells was diminished in microcapsules made with enzymatically tailored alginate and gelled in a barium solution. Secretion of endostatin was detected in lower amounts from the enzymatically tailored alginate microcapsules compared with the native alginate microcapsules. The stability of the alginate microcapsules diminished as the 293 endo cells grew inside the capsules, while empty alginate microcapsules remained stable. By using microcapsules made of fluorescenamine-labeled alginate it was clearly visualized that cells perforated the alginate microcapsules as they grew, destroying the alginate network. Soluble fluorescence-labeled alginate was taken up by the 293 endo cells, while alginate was not detected in live spheroids within fluorescence-labeled alginate microcapsules. Despite that increased stability was achieved by using enzymatically tailored alginate, the cell proliferation destroyed the alginate microcapsules with time. It is therefore necessary to use cell lines that have properties more suited for alginate encapsulation before this technology can be used for therapy.