A two-year prospective controlled study of bone mass and bone turnover in children with early juvenile idiopathic arthritis

OBJECTIVE: To explore early changes and predictors of bone mass in children with juvenile idiopathic arthritis (JIA) in order to identify patients who will develop bone mass reductions. METHODS: We conducted a prospective cohort study of 108 children with early JIA (ages 6-18 years; mean disease duration 19.3 months) who were individually matched with 108 healthy children for age, sex, race, and county of residence. Bone mass and changes in total body, spine, femur, and forearm bone mineral density and bone mineral content (BMC), body composition, growth, and biochemical parameters of bone turnover were examined at baseline and at followup a mean of 24 months later. Low bone mass was defined as a Z score >1 SD below the reference population. RESULTS: Of the 200 children evaluated at followup, the 100 healthy children had greater gains in total body BMC (P = 0.035), distal radius BMC (P < 0.001), and total body lean mass (P < 0.001) than did the 100 JIA patients. Low or very low total body BMC was observed in 24% of the patients and 12% of the healthy children. Bone formation, bone resorption, and weight-bearing activities were reduced in the patients compared with the healthy children. Multiple regression analysis showed that in patients with JIA, serum bone-specific alkaline phosphatase, serum C-telopeptide of type I collagen, and weight-bearing activities were independent predictors of changes in total body BMC. Total body BMC was lower in patients with polyarticular onset than in those with oligoarticular disease onset. CONCLUSION: Patients with JIA have moderate reductions in bone mass gains, bone turnover, and total body lean mass early in the disease course.     

Phenotype plasticity rather than repopulation from CD90/CK14+ cancer stem cells leads to cisplatin resistance of urothelial carcinoma cell lines

Background

Tumour heterogeneity and resistance to systemic treatment in urothelial carcinoma (UC) may arise from cancer stem cells (CSC). A recent model describes cellular differentiation states within UC based on corresponding expression of surface markers (CD) and cytokeratins (CK) with CD90 and CK14 positive cells representing the least differentiated and most tumourigenic population. Based on the fact that this population is postulated to constitute CSCs and the origin of cisplatin resistance, we enriched urothelial carcinoma cell lines (UCCs) for CD90 and studied the tumour-initiating potential of these separated cells in vitro.

Methods

Magnetic- and fluorescence-activated- cell sorting were used for separation of CD90⁺ and CD90^? UCCs. Distribution of cell surface markers CD90, CD44, and CD49f and cytokeratins CK14, CK5, and CK20 as well as the effects of short- and long-term treatment with cisplatin were assessed in vitro and measured by qRT-PCR, immunocytochemistry, reporter assay and flow cytometry in 11 UCCs.

Results

We observed cell populations with surface markers according to those reported in tumour xenografts. However, expression of cytokeratins did not concord regularly with that of the surface markers. In particular, expression of CD90 and CK14 diverged during enrichment of CD90⁺ cells by immunomagnetic sorting or following cisplatin treatment. Enriched CD90⁺ cells did not exhibit CSC-like characteristics like enhanced clonogenicity and cisplatin resistance. Moreover, selection of cisplatin-resistant sublines by long-term drug treatment did not result in enrichment of CD90⁺ cells. Rather, these sublines displayed significant phenotypic plasticity expressing EMT markers, an altered pattern of CKs, and WNT-pathway target genes.

Conclusions

Our findings indicate that the correspondence between CD surface markers and cytokeratins reported in xenografts is not maintained in commonly used UCCs and that CD90 may not be a stable marker of CSC in UC. Moreover, UCCs cells are capable of substantial phenotypic plasticity that may significantly contribute to the emergence of cisplatin resistance.

     

Parenting Practices and Adolescent Risk Behavior: Rules on Smoking and Drinking Also Predict Cannabis Use and Early Sexual Debut

Previous research has provided considerable support for idea that increased parental support and control are strong determinants of lower prevalence levels of adolescent risk behavior. Much less is known on the association between specific parenting practices, such as concrete rules with respect to smoking and drinking and adolescent risk behavior. The present paper examined whether such concrete parental rules (1) have an effect on the targeted behaviors and (2) predict other, frequently co-occurring, risk behaviors (i.e., cannabis use and early sexual intercourse). These hypotheses were tested in a nationally representative sample of 12- to 16-year-old adolescents in the Netherlands. We found that both types of rules were associated with a lower prevalence of the targeted behaviors (i.e., smoking and drinking). In addition, independent of adolescent smoking and drinking behaviors, parental rules on smoking predicted a lower prevalence of cannabis use and early sexual intercourse, and parental rules on alcohol use also predicted a lower prevalence of early sexual intercourse. This study showed that concrete parental rule setting is more strongly related to lower levels of risk behaviors in adolescents compared to the more general parenting practices (i.e., support and control). Additionally, the effects of such rules do not only apply to the targeted behavior but extend to related behaviors as well. These findings are relevant to the public health domain and suggest that a single intervention program that addresses a limited number of concrete parenting practices, in combination with traditional support and control practices, may be effective in reducing risk behaviors in adolescence.     

Comparison of grey scale median (GSM) measurement in ultrasound images of human carotid plaques using two different softwares

Grey scale median (GSM) measured on ultrasound images of carotid plaques has been used for several years now in research to find the vulnerable plaque. Centres have used different software and also different methods for GSM measurement. This has resulted in a wide range of GSM values and cut‐off values for the detection of the vulnerable plaque. The aim of this study was to compare the values obtained with two different softwares, using different standardization methods, for the measurement of GSM on ultrasound images of carotid human plaques. GSM was measured with Adobe Photoshop^® and with Artery Measurement System (AMS) on duplex ultrasound images of 100 consecutive medium‐ to large‐sized carotid plaques of the Beta‐blocker Cholesterol‐lowering Asymptomatic Plaque Study (BCAPS). The mean values of GSM were 35·2 ± 19·3 and 55·8 ± 22·5 for Adobe Photoshop^® and AMS, respectively. Mean difference was 20·45 (95% CI: 19·17–21·73). Although the absolute values of GSM differed, the agreement between the two measurements was good, correlation coefficient 0·95. A chi‐square test revealed a kappa value of 0·68 when studying quartiles of GSM. The intra‐observer variability was 1·9% for AMS and 2·5% for Adobe Photoshop. The difference between softwares and standardization methods must be taken into consideration when comparing studies. To avoid these problems, researcher should come to a consensus regarding software and standardization method for GSM measurement on ultrasound images of plaque in the arteries.     

Ecology of plague in Africa: response of indigenous wild rodents to experimental plague infection

The Mastomys natalensis species complex, subdivided into genetically distinct species having diploid chromosome numbers 2n = 32 and 2n = 36, is a reservoir for several zoonoses including Lassa fever and plague. This report describes a study to determine whether these sibling species and three other rodent species have different potential as reservoirs for plague. It was found that M. natalensis (2n = 32) was significantly more resistant to experimental plague infection (50% survived inoculation with 120 000 Yersinia pseudotuberculosis subsp. pestis) than was M. coucha (2n = 36) (none of which survived doses of 190 Y. pseudotuberculosis subsp.pestis). In descending order of resistance were M. natalensis, Aethomys chrysophilus, M. coucha, Tatera leucogaster and A. namaquensis. No A. namaquensis survived inoculation of 10 or more plague bacilli.     

Compared fate of small-diameter Contegras and homografts in the pulmonary position.

OBJECTIVE: This study analyzes whether small-diameter Contegras behave in the same way as small-diameter homografts, when implanted for the first time in pulmonary position. METHODS: Small-diameter conduits include 12 and 14 mm Contegras and 8-14 mm homografts. Graft dysfunction is defined as right ventricular outflow tract obstruction with peak echo-Doppler gradient>40 mmHg, or grade III/IV graft regurgitation. Graft failure is defined as need for conduit replacement or need for catheter or surgical reintervention. Thirty-eight patients who received small Contegras (n=25) and small homografts (n=13) from October 2002 to end December 2006 were studied. The most frequent indication was pulmonary atresia and ventricular septal defect (n=20; 10 associated with major aorto-pulmonary collateral arteries), followed by truncus arteriosus (n=12). Most patients' characteristics were comparable except that recipients of homografts were smaller (p for body area=0.014). Survival, freedom from graft dysfunction, failure and explantation were estimated by the Kaplan-Meier method. The log-rank test was used to compare outcomes. RESULTS: There were three early and four late deaths. No death was graft related. Survival was 80+/-8.2% for patients with Contegras and 77+/-11.7% for those with allografts: p=0.82. Mean follow-up duration is 22+/-16 months. Freedom from dysfunction for Contegras conduits decreased in the first 6 months and stabilized at 58+/-11% from month 14. For homografts it decreased only 1 year after implantation, down to 35+/-19.7% from month 31: p=0.61. Freedom from Contegras failure diminished the first 16 months to level out at 57+/-13%. No homograft failed the first 2 years. With a p-value of 0.14, homografts tended to fail less frequently. Five grafts were explanted. Freedom from explantation was similar (p=0.98): 90+/-6.7% for Contegras and 75+/-21.6% for homografts at year 3. CONCLUSION: In the first 4 years after pulmonary implantation of small-diameter Contegras and homografts, the fate of both conduits was statistically similar, in spite of different behavior. As Contegras is 'off-the-shelf' available, it constitutes a sound alternative to homograft for right ventricular outflow tract reconstruction in neonates and infants.     

Expression of 72-kDa gelatinase (matrix metailloproteinase-2) in the developing mouse craniofacial complex

Tissue remodelling is an important feature during embryogenesis. Although the matrix metalloproteinases are believed to participate in these processes, the relation between matrix metalloproteinases and tissue remodelling during craniofacial morphogenesis remains unclear. The purpose of the study was to look for the presence of enzymes involved in extracellular matrix degradation during craniofacial morphogenesis. Protein expression of the matrix metalloproteinase, 72-kDa gelatinase (matrix metalloproteinase-2, gelatinase A, 72-kDa type IV collagenase) was studied by gelatine zymography and by indirect immunofluorescence with conventional and confocal microscopy. In the anterior region of the developing mouse face, 72-kDa gelatinase was labelled mainly in the tips and peripheral regions of the nasal and facial prominences. Upon contact and fusion of the prominences, the staining was intensely localized to the zone of the fusion and the tips and peripheral regions of the nasal prominences and the maxilla. The labelling of 72-kDa gelatinase was also present in the peripheral regions of the mandible, second branchial arch, and the face around the developing eye. However, during lens vesicle formation, the staining of 72-kDa gelatinase was absent in the invaginated lens ectoderm. After the lens had, completely detached from the surface ectoderm, the staining was resumed in the corneal epithelium and mesenchyme. Gelatine zymography was used to confirm the presence of active and latent 72-kDa gelatinase in the developing mouse craniofacial complex. Collectively, these data indicate that 72-kDa gelatinase may play a significant part in localized tissue remodelling during craniofacial morphogenesis and the aberrant expression or function of the enzyme could be involved in causing facial abnormalities.