Test characteristics of quick brain MRI for shunt evaluation in children: an alternative modality to avoid radiation.

OBJECT: Quick brain magnetic resonance imaging (QB-MRI) is a rapid, radiation-free technique to detect life-threatening CSF shunt malfunction. QB-MRI has not been widely studied or adopted. The primary objective of this study was to evaluate the test characteristics of QB-MRI for detecting shunt malfunction. Test characteristics of brain computed tomography (CT) and QB-MRI were then compared. Secondary objectives included comparison of time to study completion and use of sedatives for both modalities, as well as comparison of time to study completion for QB-MRI before and after implementation of a Pediatric Emergency Department (PED) shunt clinical pathway. METHODS: A retrospective chart review was performed at 2 tertiary care hospital PEDs. The authors reviewed the charts of children who underwent QB-MRI or CT for suspected shunt malfunction between July 2008 and June 2012. They also reviewed the patients' neuroradiology reports and classified ventricular size as positive (enlarged) or negative (normal, smaller, or unchanged). Shunt malfunction was defined by surgical revision within 30 days. RESULTS: Nine hundred ninety-seven PED visits (involving 724 QB-MRIs and 273 CTs) were included. Surgical revision was performed in 235 cases (23.6%). For QB-MRI, sensitivity was 58.5% (95% CI 51.1%-65.6%) and specificity was 93.3% (90.8%-95.3%). For CT, sensitivity was 53.2% (95% CI 38.1%-67.9%) and specificity was 95.6% (92%-97.9%). The mean time to completion of QB-MRI was 115 minutes versus 83 minutes for CT (difference 32 minutes, 95% CI, 22-42 minutes, p < 0.001). The mean time from presentation to completion of QB-MRI prior to application of the CSF shunt pathway was 132 minutes versus 112 minutes after application of the CSF shunt pathway (difference 20 minutes, 95% CI 5-35 minutes, p = 0.01). Anxiolytic medications were used in 3.7% of CT studies and 4.4% of QB-MRI studies (p = 0.74). CONCLUSIONS: QB-MRI and CT have similar test characteristics for detecting CSF shunt malfunction in children and similar requirements for sedation. The longer interval from order placement to imaging completion for QB-MRI is arguably justified by reduction of radiation exposure in this population subject to frequent brain imaging.

Recombinant equine growth hormone administration: effects on synovial fluid biomarkers and cartilage metabolism in horses.

REASONS FOR PERFORMING STUDY: Recombinant equine growth hormone (reGH) has recently been evaluated for effects on body condition and wound healing. It has the potential to influence articular cartilage via stimulation of IGF-1. OBJECTIVES: To investigate effects of administration on synovial joint metabolism. METHODS: Six mature horses were given 20 microg/kg bwt reGH daily for 8 weeks by i.m. injection. Three control horses were injected with sterile water. Serum and synovial fluid samples were collected at 6, 8, 11 and 16 weeks for GH and IGF-1 assays. Articular cartilage harvested at week 16 was evaluated by Western analysis using monoclonal antibodies BC-13, BC-4, 8-A-4 and CH-3. RESULTS: Concentrations of IGF-1 in serum and synovial fluid were significantly elevated (P < 0.05) at 6 and 8 weeks in the reGH group. Glycosaminoglycan concentrations in synovial fluid were significantly less than controls at these time points, suggesting that reGH may modulate proteoglycan metabolism in articular cartilage. In the reGH group, there were not any alterations in synovial fluid content of 3B3(-) epitope or aggrecan metabolite, or in aggrecan or link protein catabolites retained within cartilage, that might be expected with development of osteoarthritis. CONCLUSIONS: Intramuscular administration of reGH may be a more efficient means of delivery of IGF-1 to joints for cartilage resurfacing initiatives. POTENTIAL RELEVANCE: We found no alterations in cartilage metabolism indicative of development of osteoarthritis.

Growth and characterization of N-methyl-N-nitrosourea-induced mammary tumors in intact and ovariectomized rats.

It is well established that 85-90% of chemically induced mammary tumors in rats will disappear or diminish significantly in size after the ovaries are removed from the animal. However, it is less well established whether a high percentage of these mammary tumors will grow back with prolonged time after ovariectomy. It is also not known what changes in gene expression take place in the tumors as they develop an independence from hormones for growth. This study was carried out to investigate this. Virgin, 50-day-old female Sprague-Dawley rats were injected with N-methyl-N-nitrosourea (MNU) at the dose of 50 mg MNU/kg body wt. When at least one mammary tumor had grown to 1.0-1.5 cm in one dimension, the animal was bilaterally ovariectomized and reduction and then re-growth of the tumors monitored. Control animals were treated identically except they were not ovariectomized when tumors appeared. Re-growths and new tumors and tumors that developed in the control rats were removed when they reached 1.0-1.5 cm in diameter and all animals were killed 25 weeks after the MNU injection. All the animals in the study (100%) developed mammary tumors after MNU injection with an average latency of 56.5 days. After ovariectomy, 93% of the tumors showed 50% or more reduction in size and 76% of the tumors could not be detected by palpation. However, in 96% of the animals where tumor reduction or disappearance occurred, a re-growth or new mammary tumor development took place with an average latency period of 52.8 days from the day of ovariectomy. Of these post-ovariectomy tumors, 36% occurred at a location where tumors had developed prior to ovariectomy, but 64% appeared at new locations. The circulating levels of 17beta-estradiol (E2) was undetectable in the ovariectomized (OVX) rats and significant reduction was seen in the serum concentrations of progesterone (P4), prolactin (PRL), growth hormone (GH) and insulin-like growth factor-I (IGF-I). The tumors from the OVX rats showed indications of progression as evident from loss of differentiation and invasive characteristics. Comparison between tumors from OVX and intact rats revealed a significantly increased expression of P450 aromatase and elevated activation of extracellular signal-regulated kinase 1 and 2, but reduced levels of the progesterone receptor and cyclin D1 in OVX rats. However, the estrogen receptor (ER) content remained similar in tumors from both groups, at least at the protein level, and so did the expression of IGF-I, IGF-II, insulin receptor substrate-1 (IRS1), IRS-2 and epidermal growth factor receptor. IGF-I receptor (IGF-IR) and ErbB-2 were expressed, respectively, in 50 and 70% of the tumors from the OVX animals, whereas these genes were expressed in 100% of the tumors from the intact rats. It is concluded that chemically induced rat mammary tumors may still depend on the ER and local syntheses of E2 and growth factors for growth initially after ovariectomy. However, as these tumors progress, they develop a more aggressive phenotype and lose their dependency on the ER and possibly growth factors.