Correction to: Investigation of brain structure in the 1-month infant.

The authors regret that, in this article, there was an error in the analyses comparing infant male and female regional brain volume differences.

Investigation of brain structure in the 1-month infant.

The developing brain undergoes systematic changes that occur at successive stages of maturation. Deviations from the typical neurodevelopmental trajectory are hypothesized to underlie many early childhood disorders; thus, characterizing the earliest patterns of normative brain development is essential. Recent neuroimaging research provides insight into brain structure during late childhood and adolescence; however, few studies have examined the infant brain, particularly in infants under 3 months of age. Using high-resolution structural MRI, we measured subcortical gray and white matter brain volumes in a cohort (N = 143) of 1-month infants and examined characteristics of these volumetric measures throughout this early period of neurodevelopment. We show that brain volumes undergo age-related changes during the first month of life, with the corresponding patterns of regional asymmetry and sexual dimorphism. Specifically, males have larger total brain volume and volumes differ by sex in regionally specific brain regions, after correcting for total brain volume. Consistent with findings from studies of later childhood and adolescence, subcortical regions appear more rightward asymmetric. Neither sex differences nor regional asymmetries changed with gestation-corrected age. Our results complement a growing body of work investigating the earliest neurobiological changes associated with development and suggest that asymmetry and sexual dimorphism are present at birth.

Mapping White Matter Microstructure in the One Month Human Brain.

White matter microstructure, essential for efficient and coordinated transmission of neural communications, undergoes pronounced development during the first years of life, while deviations to this neurodevelopmental trajectory likely result in alterations of brain connectivity relevant to behavior. Hence, systematic evaluation of white matter microstructure in the normative brain is critical for a neuroscientific approach to both typical and atypical early behavioral development. However, few studies have examined the infant brain in detail, particularly in infants under 3 months of age. Here, we utilize quantitative techniques of diffusion tensor imaging and neurite orientation dispersion and density imaging to investigate neonatal white matter microstructure in 104 infants. An optimized multiple b-value diffusion protocol was developed to allow for successful acquisition during non-sedated sleep. Associations between white matter microstructure measures and gestation corrected age, regional asymmetries, infant sex, as well as newborn growth measures were assessed. Results highlight changes of white matter microstructure during the earliest periods of development and demonstrate differential timing of developing regions and regional asymmetries. Our results contribute to a growing body of research investigating the neurobiological changes associated with neurodevelopment and suggest that characteristics of white matter microstructure are already underway in the weeks immediately following birth.

Sleep characteristics in Goldenhar Syndrome.

OBJECTIVE: To examine the characteristics of sleep in patients with Goldenhar Syndrome. DESIGN: Retrospective review of all polysomnography studies conducted at the University of North Carolina Hospitals between 2003 and 2013 on patients carrying the diagnosis of Goldenhar's Syndrome. RESULTS: A preponderance of patients demonstrated severe obstructive sleep apnea and hypercapnia. CONCLUSIONS: Patients with Goldenhar Syndrome should be screened for sleep apnea and hypercapnia.

Hip axis length variation: its correlation with anthropometric measurements in women from three ethnic groups.

UNLABELLED: We compared hip axis length (HAL) in 157 non-Hispanic white women, 292 African-American women, and 210 Mexican-American women. After adjusting for maximal hip girth, there were no residual differences in HAL by ethnicity. Differences in hip fracture risk seen between these groups cannot be explained by ethnic differences in HAL. INTRODUCTION: Hip axis length (HAL) has been reported to be an independent predictor of hip fracture. Significant ethnic differences in HAL have been noted, but no direct comparison has been made between African-American, Mexican-American, and non-Hispanic white women using the same protocol. METHODS: We compared 157 non-Hispanic white women from the Rancho Bernardo Study, 292 women from the Health Assessment Study of African-American Women, and 210 women from the Skeletal Health of Mexican-American Women Project. A standardized questionnaire was used to obtain medical history; height, weight, waist girth, and hip girth were measured; and percentage body fat and HAL were obtained using dual energy X-ray absorptiometry. All HAL comparisons were adjusted for maximum hip girth to control for differences in size magnification by fan-beam absorptiometry. RESULTS: Though there were ethnic differences in the unadjusted HAL measurement, after adjusting for hip circumference, there were no residual differences in HAL with regard to ethnicity: 10.7 cm in Mexican-American women vs. 10.8 in non-Hispanic white women and African-American women (p = 0.61). CONCLUSIONS: There were no ethnic differences in HAL in women from the three ethnic groups. Differences in fracture risk among these groups cannot be explained by ethnic differences in HAL.

A mutant of eukaryotic protein synthesis initiation factor eIF4E(K119A) has an increased binding affinity for both m7G cap analogues and eIF4G peptides.

The eukaryotic multisubunit initiation factor eIF4F is an essential component of the translational machinery. Recognition of the cap structure of mRNA, m(7)GpppN, where N is any nucleotide, by eIF4E is required for initiation of translation. Here we compare the equilibrium and thermodynamic binding characteristics of wild-type eIF4E and a high-affinity mutant, eIF4E(K119A), with those of cap analogues and eIF4G peptides. The temperature-dependent K(d) values for cap analogues were markedly lower, indicating tighter binding, with the eIF4E(K119A) mutant compared with wild-type eIF4E. Although interactions with cap analogues were found to be enthalpically driven, entropic contributions were also significant. Moreover, the binding affinities of eIF4G peptides were 2-4-fold tighter for eIF4E(K119A) than for eIF4E(wt). These results demonstrate that the binding affinity for both the mRNA cap and eIF4G peptides can be simultaneously altered by point mutations distant from either binding site. Entropic contributions to binding suggesting hydrophobic interactions are larger in the mutant protein and are most likely due to a conformational change.

Diagnostic usefulness of lung SPET in pulmonary thromboembolism: an outcome study.

The lung single photon emission tomographic (SPET) images of 985 consecutive patients referred for suspected pulmonary embolism were correlated with clinical outcome and angiography to evaluate the clinical usefulness of lung SPET compared to conventional planar ventilation/perfusion lung imaging. SPET interpretations followed the revised PIOPED criteria and clinical outcome was determined from referring physicians, hospital records, direct patient contact and county hall records. Patients were deemed to have had no clinically significant pulmonary embolism at the time of the SPET examination if, within the following 3 months: (1) the patient was alive and had no clinical evidence of pulmonary embolism or, (2) if deceased, pulmonary embolism was unlikely to have been the cause of death. Operating characteristics were based on the methods of Choi and of Simel. SPET interpretation was categorized as follows: high probability, 143 (14%); low probability, 840 (82%); intermediate, 41 (4%) (in contrast to PIOPED, with 39% intermediate interpretations). Pulmonary angiography was performed in only 4% of patients. Adequate follow-up data were available for 97% of patients. To facilitate comparison with PIOPED, either a high-probability or an intermediate-probability or an intermediate-probability study was considered to be a positive test, and either a low-probability or a normal study was considered to be a negative test. The sensitivity was 83% (PIOPED 82%), specificity 92% (PIOPED 52%), positive predictive value 62% (PIOPED 47%) and negative predictive value 97% (PIOPED 85%). The positive and negative predictive values have not been corrected for prevalence, which was approximately twice as high in the PIOPED study. Lung SPET provided accurate diagnostic information in 96% of patients and specificity was greatly improved compared to planar lung imaging reported in PIOPED. The diminished need for angiography greatly reduced the cost of evaluating patients suspected of having pulmonary embolism.

A controlled trial of physician counseling to promote the adoption of physical activity.

BACKGROUND: In accordance with one of the Year 2000 Health Objectives, the current study tests the efficacy of brief physician-based counseling to increase physical activity in sedentary patients in a nonrandomized controlled trial. METHODS: Control and intervention physicians were matched on medical practice variables. Two hundred fifty-five apparently healthy, sedentary, adult patients were recruited from 17 physician offices (mean age = 39 years, 84% female, 28% ethnic minority). Intervention physicians delivered 3 to 5 min of structured physical activity counseling during a well visit or follow-up for a chronic condition. A health educator made a brief booster phone call to patients 2 weeks after receiving physician counseling. Self-reported physical activity and stage of change (i.e., behavioral readiness to adopt or maintain activity) were collected at baseline and at 4- to 6-week follow-up. Objective activity monitoring was conducted on a subsample. RESULTS: Intervention patients reported increased walking more than control patients (+37 min/week vs. +7 min/week). There was a significant intervention effect on the activity monitor. Intervention participants also demonstrated a greater increase in readiness to adopt activity than control subjects. CONCLUSIONS: Physician-based counseling for physical activity is efficacious in producing short-term increases in moderate physical activity among previously sedentary patients.

A multisite field test of the acceptability of physical activity counseling in primary care: project PACE.

Primary health-care providers have been encouraged to counsel their patients about regular physical activity, but there are significant barriers to effective counseling. In this study a program of training and materials was tested for acceptability to providers, office staff, and patients. Primary care providers and office staff were trained to use the Physician-based Assessment and Counseling for Exercise (PACE) materials in four geographical sites in the United States. The program was tested in a variety of settings and with diverse patient populations. The acceptability of the program during a five-month study period was evaluated through structured interviews. The training was effective in preparing the providers to counsel, and the program was generally acceptable to providers, office staff, and patients. Counseling was provided in less than five minutes by 70% of providers, and most patients reported following the recommendations given. The PACE program assists providers in overcoming barriers to counseling patients about physical activity. The PACE program is potentially an important part of a national effort to enhance the adoption and maintenance of physical activity among adults.

SPECT of the cervical spine in the evaluation of neck pain after trauma.

In a retrospective study, the authors reviewed the use of SPECT in the evaluation of cervical spine abnormalities in 35 patients with persistent neck pain after trauma. Nineteen patients had normal bone SPECT studies, which, in addition to several volunteers, were used to identify tomographic landmarks and determine resolution of individual vertebrae. Sixteen patients had abnormal SPECT results. When compared to final diagnosis, this group included seven (44%) patients with recent fractures, five (31%) patients with traumatic periostitis (periosteal injury resulting from severe strain), and four patients (25%) with mild cervical strain superimposed on degenerative changes. SPECT sensitivity in the detection of recent fractures was 100% with a specificity of 78%. SPECT detected occult fractures in 7 of 35 patients (27%), including 3 patients with normal radiographs and 4 patients with equivocal radiographs. Recent fractures were excluded in six of nine patients (67%) with known fracture identified on cervical spine radiographs and none of the patients with normal SPECTs had CT or MRI evidence of recent fractures. SPECT was useful in 1) the diagnosis of occult fractures or periostitis (periosteal injury) in patients with normal radiographs, 2) characterization of radiographic abnormalities (recent versus healed fractures), 3) identification of active, possible post-traumatic osteoarthritis superimposed on chronic degenerative disease, and 4) eliminating or targeting subsequent imaging modalities, when appropriate. The authors conclude that bone SPECT has a valuable place in the diagnostic evaluation of patients with persistent neck pain after trauma.

Technetium-99m MAG3 kit formulation: preliminary results in normal volunteers and patients with renal failure.

Previous studies have shown that [99mTc]mercaptoacetyltriglycine (MAG3) purified by high performance liquid chromatography (HPLC) is a very promising new renal imaging agent which has characteristics very similar to [131I]orthoiodohippurate. An easily prepared kit formulation has been developed and evaluated in ten normal volunteers and three patients on hemodialysis. The average radiochemical purity was 96.6%. There were no adverse reactions. In the volunteers, the relative uptake +/- 1 s.d. was 49.1% +/- 2.6% for the right kidney and 50.9% +/- 2.6% or the left kidney. Urine activity was 71.4% +/- 6.4% of the injected dose at 30 min and 94.4% +/- 2.2% at 180 min. The 60-min plasma clearance was 340.0 +/- 79.0 ml/min and the volume of distribution was 5.15 +/- 1.1I. Approximately 0.5% of the injected dose was present in the gallbladder at 30-60 min postinjection. Gut activity was not present 30-60 min postinjection but reached 1% of the injected dose by 3 hr. In the hemodialysis patients, approximately 1% of the injected dose was present in the gallbladder and 0.5% in the gut at 30-60 min; gut activity increased to approximately 5% at 3 hr. In summary, results using the kit formulation compare favorably to previously published data using the HPLC purified material. Based on these preliminary results, the kit formulation is expected to have widespread clinical utility.

Technetium-99m imaging of bone trauma: reduced sensitivity caused by hydrocortisone in rabbits.

This study evaluates the effect of hydrocortisone on the sensitivity of 99mTc-scintigraphy for the detection of bone trauma in three groups of rabbits: a control group that received no hydrocortisone, a low-dose group that received 0.8 mg/kg/day, and a high-dose group that received 20 mg/kg/day. Scintigrams of the tibial diaphyses were obtained at 48 hr, 1 week, 2 weeks, and 3 weeks after surgical creation of a simulated fracture (a 1.5-mm hole in the cortex). The mean sensitivity for detecting fractures in control animals was 95% at 48 hr and 100% at all other times. Mean sensitivity for rabbits given the high dose of hydrocortisone was 41% at 48 hr. Mean sensitivity for the low-dose group was 75% at 48 hr, but this was not significantly different from the control group. Sensitivity in both groups treated with hydrocortisone improved with time. At 3 weeks, the mean was 93% in the low-dose group and 83% in the high-dose group. These data suggest that 99mTc scintigraphy may be less sensitive in detecting bone trauma in patients on glucocorticoid therapy than in patients in the general population.

Radionuclide kinetics in MIRD dose calculations.

A recent case report is reviewed and an alternative model for the radionuclide kinetics is presented; it estimates in an absorbed dose differing by a factor of two from the published calculation. Both models are consistent with observed data. Within a compartment model, one may choose to monitor a compartment of interest directly, or to monitor another compartment and (indirectly) solve for the activity in the compartment of interest. Advantages and disadvantages are reviewed.

The effect of thyroid hormone on mitochondrial biogenesis and cellular hyperplasia.

The purpose of this investigation was to study the effects of thyroid hormone treatment on the levels of DNA, RNA, and protein in hepatocytes and hepatocyte mitochondria. A preliminary investigation was conducted to establish an effective dosage of thyroid hormone. Male Sprague-Dawley rats were given daily subcutaneous injections of L-thyroxine (20, 40, or 60 micrograms/100 g body weight) and the following determinations made over a 14-day period: (1) body weight; (2) total body respiration; and (3) the activities of the mitochondrial enzymes, succinate dehydrogenase and alpha-glycerophosphate dehydrogenase. Dosages of 20 and 40 micrograms L-thyroxine/200 g body weight produced significant stimulation of (a) total body respiration and (b) succinate dehydrogenase and alpha-glycerophosphate dehydrogenase activities without any inhibitory effects on normal weight gain of the animals. Injections of 40 micrograms L-thyroxine/100 g body weight were utilized for subsequent studies. Hepatic DNA levels of treated animals were greater than age-paired control values by 28% on day 7 and 43% by day 14. Total liver RNA levels of thyroid-treated animals were 17% greater than those of controls by day 7 and 47% greater by day 14. Analyses were also performed on mitochondria quantitatively collected by rate zonal centrifugation. Total liver mitochondrial DNA levels in thyroid-treated animals were greater than age-paired controls by 79% at 7 days but only 67% at 14 days since a small gain occurred in control animals and no further increase occurred in treated rats during the second week. Mitochondrial RNA and protein from treated livers were 26% and 16% higher, respectively, than age-paired controls at day 7 and 40% and 58% higher, respectively, at day 14. The results of this study indicated that thyroid hormone treatment produces hyperplasia and an increase in mitochondrial number and mass in rat liver.

Computed tomography of necrotic hepatic metastases.

Seven patients with necrotic liver metastases were evaluated by computed tomography. The metastases demonstrated low attenuation areas varying from a small central portion to the entire lesion. Other findings included mural nodules and fluid-fluid levels. Possible etiologies for necrotic metastases are presented and their differential diagnosis is discussed.

Osteogenic sarcoma after the age of 50: a radiographic evaluation.

Twenty-four cases of primary osteosarcoma in individuals over the age of 50 are described. This represents 6% of all osteosarcomas and 80% of osteosarcomas occurring over the age of 50 at this institution. Radiographically, features were similar to osteosarcoma in younger individuals. Females were more frequently affected than males (2.4:1). The radiographic features are discussed in detail, and the differential diagnosis outlined.

Ultrasonography of necrotic hepatic metastases.

Twelve patients with sonolucent hepatic metastases studied with gray scale ultrasonography are presented. Extensive necrosis presumably accounts for the sonolucent appearance of the hepatic lesions. The spectrum of ultrasonographic features and correlations, particularly with computed tomography, are presented. The similarity between anechoic hepatic metastases and benign conditions of the liver is emphasized.