Practice MRI: Reducing the need for sedation and general anaesthesia in children undergoing MRI

The aim of this study was to evaluate the effectiveness of a practice magnetic resonance unit, in preparing children to undergo magnetic resonance procedures without general anaesthesia (GA) or sedation. The records of children who attended the practice MRI between February 2002 and April 2004 were retrospectively reviewed. Each record was assessed as to whether the child had passed or failed the practice MRI intervention. Those children who were considered to have passed and were proceeded to a clinical non‐GA MRI had the report of the clinical scan reviewed. If the scan had been reported as non‐diagnostic because of movement artefact it was classified as a failed scan, otherwise it was considered a pass. One hundred and thirty‐four children undertook a practice MRI (age range 4.1–16.1 years, median age 7.7 years, 47% boys) and 120/134 (90%) passed the practice session. In all, 117/120 (98%) subsequently had a clinical non‐GA MRI and 110/117 (94%) passed (median age 7.8 years, 47% boys). Preparation is a safe and effective method to reduce the need for sedation and GA in children undergoing a clinical MRI scan. It provides a positive medical experience for children, parents and staff, and results in cost savings for the hospital.     

A 1-year follow-up study of dynamic magnetic resonance imaging in early rheumatoid arthritis reveals synovitis to be increased in shared epitope-positive patients and predictive of erosions at 1 year

OBJECTIVES: Dynamic magnetic resonance imaging (MRI) allows visualization of the synovial membrane and measurement of synovitis within the joint. A cohort of patients with early rheumatoid arthritis (RA) were studied using MRI of the dominant wrist and clinical assessments. Associations between synovitis and the shared epitope genotype (SE) were looked for and synovitis as a predictor of joint erosion was examined. METHODS: Gadolinium-enhanced MRI scans of the dominant wrist were performed in 42 early RA patients at baseline (median disease duration = 4 months) and after 1 yr. Images were obtained at 42-s intervals over the first 6 min after gadolinium-diethylenetriamine pentaacetic acid injection using six cuts in the coronal plane, 2 mm apart. The site of maximal synovial enhancement was selected as the region of interest (ROI). The rate of enhancement (E-rate) was calculated and compared with synovitis scores from static MRI scans, clinical disease activity scores and HLA-DRB1*04/01 genotyping [sequence-specific primer polymerase chain reaction (SSP-PCR) and DNA sequencing]. RESULTS: Reproducibility of the E-rate measurement was assessed by re-evaluating 10 randomly selected scans in a blinded fashion. Intra-observer reliability was high with an intraclass correlation coefficient of 0.91, 95% confidence interval (CI) 0.65-0.97. The E-rate correlated strongly at baseline with the maximum level of synovial enhancement (E-max) (r = 0.88, P < 0.0001) and the static MRI synovitis score (r = 0.52, P = 0.0004). There was also a weaker but significant correlation between E-rate and the pain score (r = 0.29, P = 0.04). The E-rate fell from baseline to 1 yr (P = 0.02) concordant with clinical improvement after treatment with standard therapies. E-rate scores were higher in SE+ than SE - patients (F(1,25) = 5.19, P = 0.03) and were predictive of MRI erosions at 1 yr [chi-square = 5.0 (1 d.f.), P = 0.03]. The baseline C-reactive protein (CRP) was also predictive of MRI erosions at 1 yr to a similar degree [chi-square = 4.7 (1 d.f. ), P = 0.03] but the mean static synovitis score at baseline was the strongest predictor [chi-square = 9.2 (1 d.f.), P = 0.003]. CONCLUSIONS: These results show that dynamic MRI can be used to score synovitis objectively in early RA patients. Synovitis was greater in SE+ patients, suggesting an early genetic influence on joint inflammation, and was predictive for the development of erosions at 1 yr.     

The Nepal Longitudinal Study: biometric characteristics of developing eyes.

PURPOSE: To identify differences in potential biometric markers for predicting refractive error in school children. METHODS: Biometric data on 895 Tibetan children, aged 6 to 18 years, residing in Katmandu, Nepal, were collected biennially from 1992 to 2000. Measurements included cycloplegic autorefraction, A-scan ultrasonography, and video phakometry. Only those children who had been studied at least once at age 12 years or more were included in the analysis. Subjects were divided into two groups: a myopia group if the refractive error was myopic by more than -0.50 D and a nonmyopia group if the refractive error was maximally myopic by -0.50 D, expressed as a spherical equivalent error in the left eye. RESULTS: Biometric measures that differed significantly with increasing age between the two refractive groups included: anterior chamber depth + 0.012 mm/year (p = 0.014), anterior lens radius of curvature + 0.073 mm/year (p = 0.001), lens power -0.059 D/year (p = 0.082), lens thickness -0.005 mm/year (p = 0.02), and vitreous chamber depth + 0.084 mm/year (p < 0.001). Corneal radii of curvature of the myopic group were steeper at all ages by 0.09 mm (p < 0.001), but the rate of change with age was equivalent across the refractive groups. CONCLUSIONS: Compared with those who remained nonmyopic, children who developed myopia had a crystalline lens that was initially thicker and steeper, and a vitreous chamber that was initially shorter. With age, children who became myopic developed greater lens thinning, greater flattening of the anterior lens surface radius, and a greater increase in vitreous chamber depth than their nonmyopic counterparts.     

Newborn hearing screening: costs of establishing a program.

OBJECTIVE: To evaluate the costs and performance characteristics associated with the start-up phase of Universal Newborn Hearing Screening Programs, one utilizing automated auditory brainstem response (AABR) and the other using transient evoked otoacoustic emissions (TEOAE). STUDY DESIGN: Economic and performance data were collected at the initiation of both screening programs. Data were collected until 1500 newborn infants were screened or until a referral rate for further audiologic evaluation at hospital discharge of less than or equal to 5% was achieved. Data collected included screening pass/fail rates, referral rates and personnel, equipment, and supply utilization. Actual costs of personnel, equipment, and supplies were used. Statistical comparisons of proportions using z-statistic with the one-tailed test and an alpha of 0.01 were made. RESULTS: Screening in the AABR program was performed by neonatal nurses, whereas screening in the TEOAE program was performed by master's level audiologists. The average age at initial screen was 29 hours for TEOAE, and 9.5 hours for AABR. Eighty-four percent of infants was screened within 24 hours in the AABR program, in contrast to 35% in the TEOAE program. Throughout the duration of the study, the referral rate at hospital discharge remained approximately 15% for the TEOAE program. The AABR referral rate began at 8% and was less than 4% at the completion of the study. Pre-discharge total costs for initiating and establishing the programs were US$49,316 for TEOAE and US$47,553 for AABR. Cost per infant screened was US$32.23 and US$33.68, respectively. When post-discharge screening and diagnostic evaluation costs were included, the total cost per infant screened was US$58.07 for TEOAE and US$45.85 for AABR. CONCLUSION: AABR appears to be the preferred method for universal newborn hearing screening. AABR was associated with the lowest costs, achieved the lowest referral rates at hospital discharge, and had the quickest learning curve to achieve those rates.     

Granulocyte-macrophage colony-stimulating factor (GM-CSF) priming with successive concomitant low-dose Ara-C for elderly patients with secondary/refractory acute myeloid leukemia or advanced myelodysplastic syndrome.

Patients with advanced MDS and secondary AML respond poorly to chemotherapy. Granulocyte-macrophage colony-stimulating factor (GM-CSF) can stimulate proliferation of leukemic blasts and sensitize these cells to the cytotoxic effects of S-phase-specific drugs. This is the first report of safety and efficacy of GM-CSF prior to and during cytarabine in a low-dose, intermittent regimen for elderly patients with poor risk acute myelogenous leukemia or myelodysplastic syndrome. Twenty patients, age 68 to 86 years, each received 250 microg/m2 of GM-CSF (Sargramostatin; Immunex, Seattle, WA, USA) subcutaneously (s.c.) or intravenously (i.v.) for 3 days followed by GM-CSF at the same dose and cytarabine 100 mg/m2 i.v. for 3 days. GM-CSF and cytarabine were both administered for 3 days during weeks 2 and 3 followed by a 3-week rest period. Rates of CR and PR were 20% and 40%, respectively. These included clinically significant resolution of cytopenias and transfusion requirements. Many of the responding patients had been heavily pretreated prior to enrollment. One- and 2-year survival estimates are 44% and 19%, respectively. Myelosuppression was the most significant toxicity. Our findings suggest that this novel combination of GM-CSF with sequential and concomitant low-dose cytarabine can benefit patients with poor risk myeloid malignancies.     

Goserelin versus cyclophosphamide, methotrexate, and fluorouracil as adjuvant therapy in premenopausal patients with node-positive breast cancer: The Zoladex Early Breast Cancer Research Association Study.

PURPOSE: Current adjuvant therapies have improved survival for premenopausal patients with breast cancer but may have short-term toxic effects and long-term effects associated with premature menopause. PATIENTS AND METHODS: The Zoladex Early Breast Cancer Research Association study assessed the efficacy and tolerability of goserelin (3.6 mg every 28 days for 2 years; n = 817) versus cyclophosphamide, methotrexate, and fluorouracil (CMF) chemotherapy (six 28-day cycles; n = 823) for adjuvant treatment in premenopausal patients with node-positive breast cancer. RESULTS: Analysis was performed when 684 events had been achieved, and the median follow-up was 6 years. A significant interaction between treatment and estrogen receptor (ER) status was found (P =.0016). In ER-positive patients (approximately 74%), goserelin was equivalent to CMF for disease-free survival (DFS) (hazard ratio [HR], 1.01; 95% confidence interval [CI], 0.84 to 1.20). In ER-negative patients, goserelin was inferior to CMF for DFS (HR, 1.76; 95% CI, 1.27 to 2.44). Amenorrhea occurred in more than 95% of goserelin patients by 6 months versus 58.6% of CMF patients. Menses returned in most goserelin patients after therapy stopped, whereas amenorrhea was generally permanent in CMF patients (22.6% v 76.9% amenorrheic at 3 years). Chemotherapy-related side effects such as nausea/vomiting, alopecia, and infection were higher with CMF than with goserelin during CMF treatment. Side effects related to estrogen suppression were initially higher with goserelin, but when goserelin treatment stopped, reduced to a level below that observed in the CMF group. CONCLUSION: Goserelin offers an effective, well-tolerated alternative to CMF in premenopausal patients with ER-positive and node-positive early breast cancer.     

Cytokine and adhesion molecule expression in primary human endothelial cells stimulated with fever-range hyperthermia.

Migration of blood-borne lymphocytes into lymphoid tissues and sites of inflammation is initiated by vascular adhesion molecules and proinflammatory cytokines. Previous in vivo studies have shown that febrile temperatures dynamically stimulate adhesion in differentiated high endothelial venules (HEV), which are portals for lymphocyte extravasation. This report examines the direct effect of fever-range hyperthermia on the expression of adhesion molecules and cytokines by primary cultured endothelial cells. In both macrovascular (HUVEC) and microvascular (HMVEC) endothelial cells, fever-range hyperthermia (40 degrees C for 6-12 h) did not affect expression of adhesion molecules (ICAM-1, E-selectin, VCAM-1, P-selectin, PECAM-1, PNAd, MAdCAM-1), cytokine release (IL-1beta, TNF-alpha, IFN-gamma, IL-6, IL-11, IL-12, IL-13), or chemokine secretion (IL-8, RANTES, MCP-1, MIP-1beta, MIG). This is in contrast to the stimulatory effects of TNF-alpha or 43 degrees C heat shock. However, a novel role for fever-range hyperthermia was identified in augmenting actin polymerization in cultured endothelial cells and enhancing the ability of endothelial-derived factors to transactivate the alpha4beta7 integrin lymphocyte homing receptor. These findings provide insight into the tightly regulated effects of fever-range hyperthermia that exclude induction of adhesion in non-activated endothelium of normal blood vessels. Through these mechanisms, it is proposed that febrile temperatures associated with infection or clinical hyperthermia avoid the unproductive exodus of lymphocytes to non-involved extralymphoid tissues while simultaneously promoting lymphocyte delivery to sites of immune activation.     

Relation between Irofulven (MGI-114) systemic exposure and tumor response in human solid tumor xenografts.

Irofulven is a novel, small molecular weight semisynthetic compound, derived from a family of mushroom toxins known as illudins. This DNA alkylating agent has a chemical structure unlike any other chemotherapeutic agent in clinical use. The molecule is currently being studied in several Phase I, II, and III trials. The objectives of this study were to evaluate the antitumor activity of Irofulven in a panel of 20 pediatric solid tumor xenografts and to relate the Irofulven systemic exposure, defined as area under the concentration time curve, to the antitumor dose associated with tumor regression in the tumor models. Irofulven was administered i.v. daily for 5 days with courses repeated every 21 days for a total of three cycles. The minimum effective dose of Irofulven causing objective regression (> or =50% volume regression) of advanced tumors was determined for each of 19 of 20 independently derived tumor models (12 brain tumors, 4 neuroblastomas, and 4 rhabdomyosarcomas). At the maximum tolerated dose for three cycles of treatment (4.6 mg/kg/day) objective regressions were determined in 14 of 18 tumor lines (78%). However, the dose-response relationship was acute. At 2 mg/kg only 3 of 15 tumors tested demonstrated objective regressions, and in 3 additional tumors volume regressions were not achieved at a higher dose level (3 mg/kg), hence were not additionally tested. After administering the maximum tolerated dose (tolerated for one or two cycles of treatment) of Irofulven, 7 mg/kg, to mice bearing sensitive and resistant human tumors plasma concentration-time profiles were determined. Tumors were highly sensitive to Irofulven, but the systemic exposure required for a significant rate of objective response in this panel of tumors is in excess of that achievable in patients at tolerable doses, using this schedule of drug administration.     

Precision of quantitative ultrasound: comparison of three commercial scanners

Quantitative ultrasound (QUS) measurements of bone have been shown to be independent predictors of osteoporotic fracture risk. Drawbacks of this technique have included the precision of the scanners, which is said to be poorer than in dual-energy X-ray absorptiometry (DXA), in part due to difficulty in repositioning of the foot in an os calcis system and difficulty in comparison across different technologies. A new type of QUS scanner has been introduced that produces an image of the area scanned and is believed to improve precision by aiding repositioning. In this study, we compare three scanners: a dry system (McCue CUBA Clinical); a nonimaging water-bath system (Lunar Achilles(+)); and an imaging water-bath system (Osteometer DTU-One). Short-term phantom precision was calculated by repeating measurements ten times in succession on the manufacturer-supplied phantom. Long-term phantom precision was calculated by examining the phantom measurements over a 6 month period. In vivo precision was calculated in 26 normal volunteers (19 women, 7 men) and 20 women with osteoporosis. Monitoring time intervals (MTIs) were also calculated using the manufacturer's normative database. The MTI is the period between scans required to show that a "true" change has occurred, and was between 0.5 year for stiffness (a derived index produced by the Lunar Achilles instrument) and >5 years for all other measurements. The imaging system did not seem to improve precision. Precision for the QUS phantom was similar to that of DXA with a coefficient of variation (CV) of around 1.5% for BUA and <1% for speed of sound (SOS). The precision was such that the technique may be considered for monitoring skeletal changes. However, the change of bone mass at the os calcis in response to treatment was slow, which made the time needed to wait before assessing change, on the whole, longer than that for DXA. An exception may be the Lunar Achilles "stiffness" parameter, but this can only be determined in a longitudinal, comparative treatment study.