Prevalent vertebral fractures among children initiating glucocorticoid therapy for the treatment of rheumatic disorders

Objective

Vertebral fractures are an under‐recognized problem in children with inflammatory disorders. We studied spine health among 134 children (87 girls) with rheumatic conditions (median age 10 years) within 30 days of initiating glucocorticoid therapy.

Methods

Children were categorized as follows: juvenile dermatomyositis (n = 30), juvenile idiopathic arthritis (n = 28), systemic lupus erythematosus and related conditions (n = 26), systemic arthritis (n = 22), systemic vasculitis (n = 16), and other conditions (n = 12). Thoracolumbar spine radiograph and dual x‐ray absorptiometry for lumbar spine (L‐spine) areal bone mineral density (BMD) were performed within 30 days of glucocorticoid initiation. Genant semiquantitative grading was used for vertebral morphometry. Second metacarpal morphometry was carried out on a hand radiograph. Clinical factors including disease and physical activity, calcium and vitamin D intake, cumulative glucocorticoid dose, underlying diagnosis, L‐spine BMD Z score, and back pain were analyzed for association with vertebral fracture.

Results

Thirteen vertebral fractures were noted in 9 children (7%). Of these, 6 patients had a single vertebral fracture and 3 had 2–3 fractures. Fractures were clustered in the mid‐thoracic region (69%). Three vertebral fractures (23%) were moderate (grade 2); the others were mild (grade 1). For the entire cohort, mean ± SD L‐spine BMD Z score was significantly different from zero (?0.55 ± 1.2, P < 0.001) despite a mean height Z score that was similar to the healthy average (0.02 ± 1.0, P = 0.825). Back pain was highly associated with increased odds for fracture (odds ratio 10.6 [95% confidence interval 2.1–53.8], P = 0.004).

Conclusion

In pediatric rheumatic conditions, vertebral fractures can be present prior to prolonged glucocorticoid exposure.

     

Chromosomal Alterations in Pure Nonneoplastic Breast Lesions: Implications for Breast Cancer Progression

Introduction  

Columnar cell lesions (CCL) and atypical ductal hyperplasia (ADH) frequently coexist and share molecular changes with in situ and invasive components, suggesting that CCL and ADH may be precursors to breast cancer. These conclusions are largely based on studies examining CCL and/or ADH from patients diagnosed with more advanced disease. We assessed allelic imbalance (AI) in pure CCL or ADH specimens to characterize molecular changes in nonneoplastic breast lesions.     

Molecular signatures of lymph node status by intrinsic subtype: gene expression analysis of primary breast tumors from patients with and without metastatic lymph nodes

Background

Identification of a gene expression signature in primary breast tumors that could classify patients by lymph node status would allow patients to avoid the morbidities of surgical disruption of the lymph nodes. Attempts to identify such a signature have, to date, been unsuccessful. Because breast tumor subtypes have unique molecular characteristics and different sites of metastasis, molecular signatures for lymph node involvement may vary by subtype.

Methods

Gene expression data was generated from HG U133A 2.0 arrays for 135 node positive and 210 node negative primary breast tumors. Intrinsic subtype was assigned using the BreastPRS. Differential gene expression analysis was performed using one-way ANOVA using lymph node status as the variable with a False-discovery rate <0.05, to define significance.

Results

Luminal A tumors were most common (51%) followed by basal-like (27%), HER2-enriched (14%) luminal B (7%) and normal-like (1%). Basal-like and luminal A tumors were less likely to have metastatic lymph nodes (35% and 37%, respectively) compared to luminal B or HER2-enriched (52% and 51%, respectively). No differentially expressed genes associated with lymph node status were detected when all tumors were considered together or within each subtype.

Conclusions

Gene expression patterns from the primary tumor are not able to stratify patients by lymph node status. Although the primary breast tumor may influence tumor cell dissemination, once metastatic cells enter the lymphatics, it is likely that characteristics of the lymph node microenvironment, such as establishment of a pre-metastatic niche and release of pro-survival factors, determine which cells are able to colonize. The inability to utilize molecular profiles from the primary tumor to determine lymph node status suggest that other avenues of investigation, such as how systemic factors including diminished immune response or genetic susceptibility contribute to metastasis, may be critical in the development of tools for non-surgical assessment of lymph node status with a corresponding reduction in downstream sequelae associated with disruption of the lymphatics.

     

Retinal detachment in the morning glory anomaly

The morning glory anomaly is a rare congenital clinical entity that results from abnormal optic nerve development. In our series of 30 patients, followed for a mean duration of 10.3 years, 11 developed associated retinal detachments. These detachments followed a variable clinical course, including spontaneous reattachment and even redetachment, and may result from an abnormal communication between the subarachnoid space of the optic nerve and the subretinal space, allowing cerebrospinal fluid to accumulate subretinally. The clinical findings (including ultrasonography, computed tomography, and electrophysiologic testing), natural history, complications, and therapeutic indications are discussed.     

Differences between calcium channel inhibitors in their effects on phencyclidine-induced behavioral stimulation in mice

Sixteen calcium channel inhibitors (CCI's) were tested in a model utilizing phencyclidine (PCP)-induced behavioral stimulation in mice. There were marked differences in the effects of CCI's both within subclasses and between subclasses of CCI's. All of the dihydropyridines and possibly flunarizine were effective in blocking PCP-induced behavioral stimulation. Papaverine derivatives, including verapamil, and several other CCI's, were ineffective.     

Associations of dietary fat, regional adiposity, and blood pressure in men

Mediterranean populations have low incidence rates of cardiovascular disease and hypertension that may be due, in part, to dietary factors, particularly a relatively high intake of monounsaturated fat as olive oil. In this study, nutritional components (as grams per 4200 kJ) (1 kcal = 4.2 kJ) from three-day food records were examined in association with resting blood pressure in a cross-sectional survey of 76 sedentary middle-aged American men, aged 30 to 55 years, with resting blood pressures below 160/100 mm Hg. Systolic and diastolic blood pressures correlated significantly and inversely with monounsaturated fat consumption. Polyunsaturated fat consumption also correlated inversely with diastolic blood pressure; however, this relationship became nonsignificant when adjusted for an index of regional adiposity that characterizes the male-type obesity pattern. Detailed analyses of specific fatty acids showed that the correlations with monounsaturates were specific to oleic acid, and the correlation with polyunsaturates was specific to linoleic acid. Multiple regression analysis suggested that 18.2% of the variance in systolic blood pressure and 23.2% of the variance in diastolic blood pressure were related to monounsaturated and polyunsaturated fat consumption and regional adiposity. Thus, increased consumption of monounsaturated fat is related inversely to resting blood pressure, although causality remains to be determined.