Repair of erosions in rheumatoid arthritis does occur. Results from 2 studies by the OMERACT Subcommittee on Healing of Erosions

The committee was charged with determining whether healing of erosions in rheumatoid arthritis (RA) occurs. Two exercises were performed: The first asked the committee members, as a panel of experts, to express agreement or disagreement with the presence of improvement and features of bone reaction to injury in images submitted by members as examples of healing. The second presented panel members with 28 pairs of serial images, 14 chosen to illustrate progression and 14 chosen to illustrate repair. Agreement was tested on 8 items: global judgment on which image in the pair was better, relative size of the erosion in the 2 images, judgment on which image was first, presence and extent of sclerosis, cortication, filling-in, remodeling, and reconstituting normal structure. Our results showed good agreement, among the 15 respondents, on global assessment of which image was better and which image showed the smaller erosion. Correct assignment of sequence was only slightly better than expected by chance (in 65% of the cases). Agreement was poor regarding the presence of morphologic features of bone repair. A majority of a panel of experts agreed on which 2nd images in a set of paired, serial images represented improvement and which showed progression based on global assessment of which was better and on size of erosion. Features of bone repair were not distinctive and did not enable the panel to deduce the correct sequence of the serial images. This study provides evidence that repair of bone damage in RA does occur, resulting in some degree of improvement, which was recognized by a majority of a panel of experts.     

Prediagnostic circulating carotenoid levels and the risk of non-Hodgkin lymphoma: the Multiethnic Cohort

This analysis examined the association of non-Hodgkin lymphoma (NHL) with prediagnostic carotenoid levels, a marker for a diet rich in fruits and vegetables. We conducted a nested case-control study within the Multiethnic Cohort with 271 NHL cases and 538 controls matched on sex, ethnicity, location (Hawaii or Los Angeles), birth year, date and time of blood draw, and hours fasting before blood draw. Serum carotenoid levels were obtained by high-pressure liquid chromatography with photodiode array detection. Conditional logistic regression was used to calculate odds ratios (ORs) according to tertiles of serum carotenoids and trend tests using continuous variables. Higher total serum carotenoids (OR(T3 vs T1) = 0.66 [0.46-0.96]; P(trend) = .02), lycopene (OR = 0.54 [0.38-0.78]; P(trend) = .003), and α-cryptoxanthin (OR = 0.53 [0.36-0.78]; P(trend) = .003) were associated with a lower risk of NHL. For retinol (OR = 0.90 [0.61-1.33]; P(trend) = .04), a statistically significant inverse linear trend was detected. Risk estimates remained unchanged with adjustment for NHL risk factors and were similar in analyses stratified by sex and ethnicity; heterogeneity with NHL subtype was detected only for β-carotene. Other carotenoids, including α-carotene, β-carotene, lutein, β-cryptoxanthin, and zeaxanthin, showed no association with risk. These data provide support for a protective role of carotenoid-rich fruits and vegetables in the etiology of NHL.     

Activated protein C reduces tissue hypoxia, inflammation, and apoptosis in traumatized skeletal muscle during endotoxemia

OBJECTIVE: Extensive surgical trauma leads to activation of the coagulation cascade and is often complicated by systemic inflammation and infection. Activated protein C, a natural coagulatory inhibitor, was recently shown to reduce mortality in septic patients. We herein report on the actions of activated protein C on skeletal muscle injury in experimental endotoxemia. DESIGN: Prospective controlled animal study. SETTING: University animal research facility. SUBJECTS: Male Sprague-Dawley rats. INTERVENTIONS: Closed soft tissue trauma was applied on the left hind limb of pentobarbital-anesthetized rats. Six hours later endotoxemia was induced by intraperitoneal injection of Escherichia coli lipopolysaccharide. An equivalent volume of physiologic saline was given in controls. At the same time point, treatment of animals was started by continuous intravenous application of activated protein C (24 microg/kg.hr) or vehicle solution over 18 hrs. Twenty-four hours after trauma, the extensor digitorum longus muscle was microsurgically exposed and analyzed by means of high-resolution multifluorescence microscopy. MEASUREMENTS AND MAIN RESULTS: Endotoxemia aggravated traumatized muscle injury, as evidenced by reduced nutritive perfusion, increased tissue hypoxia, enhanced leukocyte-endothelial cell interaction, and apoptotic myocyte cells (249 +/- 17 cm/cm vs. 298 +/- 22 cm/cm; reduced nicotinamide adenine dinucleotide [NADH], 149 +/- 15 arbitrary units [AU] vs. 130 +/- 13 AU; 417 +/- 79 cells/mm vs. 344 +/- 77 cells/mm and 62 +/- 9 cells/mm vs. 31 +/- 5 cells/mm). Therapeutic intervention with activated protein C 6 hrs after trama protected nutritive perfusion and tissue oxygenation (341 +/- 24 cm/cm and 115 +/- 8 AU) and reduced inflammatory leukocyte adherence (185 +/- 60 cells/mm) and cellular apoptosis (15 +/- 4 cells/mm). Of note, the protection of traumatized muscle tissue by activated protein C was also maintained during endotoxemia, as indicated by a functional capillary density of 379 +/- 10 cm/cm, a NADH-fluorescence of 102 +/- 6 AU, a leukocyte adherence of 82 +/- 12 cells/mm, and a myocyte apoptosis of 28 +/- 4 cells/mm. CONCLUSIONS: Microcirculatory injury of traumatized skeletal muscle tissue is enhanced by intravenous endotoxin application in this model of soft tissue trauma. Activated protein C ameliorates microcirculatory dysfunction and tissue injury, in particular in traumatized animals during endotoxemia.     

Current Concepts Review - Fractures in the Region of the Elbow

Elbow injuries continue to rise with increased athletic activity and life expectancy. Knowledge of anatomy and biomechanics of this sophisticated joint, various injury patterns, and the implication of injury to the static and dynamic stabilizers will result in improvement in specific diagnosis, and therapy. The surgical treatment of trauma to the adult elbow has evolved rapidly in recent years and many useful concepts and techniques have been established. This paper reviews the published scientific data and current opinion available to guide patient care.     

The relation of soy intake and isoflavone levels in nipple aspirate fluid.

Given the possible breast cancer preventive effects of isoflavones, substances with an estrogen-like structure occurring in soybeans, it is of interest to assess levels directly in the breast. The objective of this pilot study was to measure isoflavones in nipple aspirate fluid. In a pilot study with 11 women, nipple aspirate fluid and urine samples were collected at baseline and after 1 month of consuming two servings of soymilk per day. In a parallel investigation, one woman donated nipple aspirate fluid, blood, and urine on the same day after consuming different amounts of soy for 9 days. Nipple aspirate fluid was collected with an aspirator, diluted 1 : 11, and stored at -20 degrees C. Isoflavonoids in nipple aspirate fluid, serum, and urine were liquid-liquid extracted after enzymatic hydrolysis followed by liquid chromatography electrospray ionization high resolution tandem mass spectrometry analysis using triply C labeled internal isoflavonoid standards. After the 30-day soy intervention, median nipple aspirate fluid yield changed very little (P=0.47), whereas urinary isoflavonoid excretion (P=0.04) and isoflavonoid levels in nipple aspirate fluid (P=0.12) increased substantially. For the nine samples collected in one participant, isoflavonoids measured in nipple aspirate fluid, plasma, and urine were highly correlated with the number of daily soy servings and with each other. This pilot study indicates that isoflavonoids in nipple aspirate fluid are 10 times lower than in plasma and are closely related to levels of isoflavonoids in urine and plasma. These findings show that isoflavonoids are present in breast fluid and may act directly on breast tissue.     

Serotonin fibre densities in subcortical areas: differential effects of isolated rearing and methamphetamine

Serotoninergic neurons interact with dopaminergic cells on all levels and are physiologically affected by both isolated rearing (IR) and a single early methamphetamine (MA) injection. We therefore checked for anatomical effects of both interventions by immunohistochemically staining serotonin fibres and assessing fibre densities in the caudate-putamen (CPu), nucleus accumbens (NAc) and amygdala of Mongolian gerbils. IR led to significantly increased 5-HT fibre densities in the dorsal part of the CPu and in the central and basolateral amygdala. No effects were seen in the ventral CPu, in the NAc and in the lateral amygdala. The early MA injection resulted in a denser 5-HT innervation in the dorsomedial and ventromedial CPu, in the NAc shell of animals reared in an enriched environment and in the NAc core of both rearing conditions, leaving the lateral CPu and the amygdala unaffected. Thus, the single pharmacological versus the environmental challenge exerts an almost complementary effect on the 5-HT innervation in different areas of the brain, which demonstrates that systemic interactions, e.g. with dopaminergic and glutamatergic afferents, must be taken into account when the seemingly uniform 5-HT projections are investigated.     

3D versus 2D ultrasound: accuracy of volume measurement in human cadaver kidneys

RATIONALE AND OBJECTIVES: Comparison of the accuracy of 3D and 2D ultrasound in assessing the volume of human cadaver kidneys. MATERIALS AND METHODS: Before autopsy the volume of 22 kidneys was assessed from a 3D data set after manually tracing organ contours (3D volumetry) and by applying a 3D ellipsoid formula both on a 3D data set and 2D images. Measurements by water-displacement served as the gold standard. RESULTS: 3D volumetry showed a mean absolute deviation of 31 mL (18.5%) compared with the mean gold standard measurement (168 mL), yielding a concordance correlation (Lin's rho(c) ) of 0.71. Calculation based on the ellipsoid formula revealed a mean absolute deviation of 37 mL (22.0%) when applied on the 3D data set (rho(c) = 0.65) and of 42 mL (25.0%) when applied on 2D images (rho(c) = 0.61). CONCLUSIONS: 3D volumetry showed a satisfactory concordance correlation and is superior to volume calculation based on the ellipsoid formula either applied to a 3D data set or to conventional 2D images in assessing the volume of human cadaver kidneys.     

Contents Vol. 60(2002)

Volume Contents

Contents Vol. 60(2002)