Differential developmental trajectories of magnetic susceptibility in human brain gray and white matter over the lifespan

As indicated by several recent studies, magnetic susceptibility of the brain is influenced mainly by myelin in the white matter and by iron deposits in the deep nuclei. Myelination and iron deposition in the brain evolve both spatially and temporally. This evolution reflects an important characteristic of normal brain development and ageing. In this study, we assessed the changes of regional susceptibility in the human brain in vivo by examining the developmental and ageing process from 1 to 83 years of age. The evolution of magnetic susceptibility over this lifespan was found to display differential trajectories between the gray and the white matter. In both cortical and subcortical white matter, an initial decrease followed by a subsequent increase in magnetic susceptibility was observed, which could be fitted by a Poisson curve. In the gray matter, including the cortical gray matter and the iron‐rich deep nuclei, magnetic susceptibility displayed a monotonic increase that can be described by an exponential growth. The rate of change varied according to functional and anatomical regions of the brain. For the brain nuclei, the age‐related changes of susceptibility were in good agreement with the findings from R2^* measurement. Our results suggest that magnetic susceptibility may provide valuable information regarding the spatial and temporal patterns of brain myelination and iron deposition during brain maturation and ageing. Hum Brain Mapp 35:2698–2713, 2014. © 2013 Wiley Periodicals, Inc .     

Extracting data from electronic medical records: validation of a natural language processing program to assess prostate biopsy results

Objective

The extraction of specific data from electronic medical records (EMR) remains tedious and is often performed manually. Natural language processing (NLP) programs have been developed to identify and extract information within clinical narrative text. We performed a study to assess the validity of an NLP program to accurately identify patients with prostate cancer and to retrieve pertinent pathologic information from their EMR.

Materials and methods

A retrospective review was performed of a prospectively collected database including patients from the Southern California Kaiser Permanente Medical Region that underwent prostate biopsies during a 2-week period. A NLP program was used to identify patients with prostate biopsies that were positive for prostatic adenocarcinoma from all pathology reports within this period. The application then processed 100 consecutive patients with prostate adenocarcinoma to extract 10 variables from their pathology reports. The extraction and retrieval of information by NLP was then compared to a blinded manual review.

Results

A consecutive series of 18,453 pathology reports were evaluated. NLP correctly detected 117 out of 118 patients (99.1 %) with prostatic adenocarcinoma after TRUS-guided prostate biopsy. NLP had a positive predictive value of 99.1 % with a 99.1 % sensitivity and a 99.9 % specificity to correctly identify patients with prostatic adenocarcinoma after biopsy. The overall ability of the NLP application to accurately extract variables from the pathology reports was 97.6 %.

Conclusions

Natural language processing is a reliable and accurate method to identify select patients and to extract relevant data from an existing EMR in order to establish a prospective clinical database.     

Not small adults: the emerging role of pediatric pain services

Purpose

This review article explores the need for specialized pain care for children and adolescents and provides some historical context for our current knowledge base and clinical practice.

Principal findings

Pediatric patients have specialized needs with respect to assessment and management of pain. Acute pain care is modified by developmental considerations in both these areas; chronic pain encompasses a wide range of complex developmental, social, and psychological factors requiring the skills of different health disciplines to provide the best care.

Conclusions

Awareness of children’s pain has increased dramatically over the past three decades, and Canadians have performed a leadership role in much of the research. Specific multidisciplinary teams are a more recent phenomenon, but they are shown to be more effective and probably more cost effective than traditional treatment models. Important gaps in availability of resources to manage these patients remain.     

Kyphoplasty and vertebroplasty

Percutaneous vertebroplasty is the injection of a vertebral compression fracture (VCF) with bone cement, generally polymethylmethacrylate. Percutaneous kyphoplasty is the placement of balloons into the vertebral body with an inflation/deflation sequence to create a cavity before the cement injection. These procedures are most often performed in a percutaneous fashion on an outpatient (or short stay) basis. The procedure is indicated for painful VCFs due to osteoporosis or malignancy, and painful hemangiomas. The procedure may have efficacy in painful vertebral metastasis and traumatic compression fractures. Much evidence favors the use of this procedure for pain associated with these disorders. The overall risks of the procedure are low, but serious complications (including spinal cord compression) can occur. With good patient selection and careful technique, these complications are avoidable, making the risk-to-benefit ratio highly favorable.     

Chronic liposome administration in mice: effects on reticuloendothelial function and tissue distribution

Liposomes have a pronounced tendency to localize in the reticuloendothelial (RE) system, a major host defense system. We have examined, in mice, the effect of chronic i.v. administration of low to moderate liposome doses on drug metabolism, phagocytic index and spleen and liver size. Little effect on the rate of pentobarbital metabolism was noted, except when mice received 80 mg/kg of sphingomyelin-containing liposomes in a series of 10 injections over 3.5 weeks. Impairment of RE phagocytic function was found to be related to liposome size and composition, size and frequency of liposome dose and the presence of lipid peroxides. The effects on tissue distribution of liposome-entrapped [14C]sucrose was also determined in mice receiving chronic liposome injections. In RE blockaded mice there was a consistent trend in favor of decreased liver uptake and increased spleen uptake. No significant uptake of liposome contents was seen in non-RE tissues even in mice with severe RE blockade, indicating that the induction of RE blockade by predosing with empty liposomes may not be a successful strategy for increasing liposome uptake to non-RE tissues. Liver to spleen ratios of [14C]sucrose appeared to be a sensitive method for quantitating RE blockade. Sphingomyelin-containing liposomes produced the greatest RE blockade, distearoylphosphatidylcholine-cholesterol liposomes were intermediate and egg phosphatidylcholine-cholesterol liposomes produced the least impairment in RE function. Liposomes which contained 1% vitamin E as an antioxidant had slightly less effect on RE function than liposomes not containing vitamin E.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pathogenesis of unexplained drowning: new insights from a molecular autopsy

OBJECTIVE: To perform a molecular autopsy involving the RyR2-encoded cardiac ryanodine receptor/calcium release channel to determine whether mutations responsible for catecholaminergic polymorphic ventricular tachycardia (CPVT) represent a novel pathogenic basis for unexplained drownings. METHODS: A cardiac channel molecular autopsy was performed on 2 individuals who died of unexplained drowning and whose cases were referred to the Sudden Death Genomics Laboratory at the Mayo Clinic in Rochester, Minn. Comprehensive mutational analysis of all 60 protein-encoded exons of the 5 long QT syndrome-causing cardiac channel genes and a targeted analysis of 18 RyR2 exons known to host RyR2-mediated CPVT-causing mutations (CPVT1) was performed using polymerase chain reaction, denaturing high-performance liquid chromatography, and DNA sequencing. RESULTS: Both individuals harbored novel mutations in RyR2. Postmortem mutational analysis revealed a familial missense mutation in exon 14, R414C, in a 16-year-old girl. A 9-year-old boy possessed a sporadic missense mutation in exon 49, V2475F. Both amino acid positions involve highly conserved residues that localize to critical functional domains in the calcium release channel. Neither substitution was present in 1000 reference alleles. CONCLUSIONS: This molecular autopsy study provides proof of principle that RyR2 mutations can underlie some unexplained drownings. A population-based genetic epidemiology study that involves molecular autopsies of individuals who die of unexplained drowning is needed to determine the prevalence and spectrum of KCNQ1 and now RyR2 mutations as potential pathogenic mechanisms for drowning.     

Tailoring the psychotherapy to the borderline patient

Views still differ as to the optimal psychodynamic treatment of borderline patients. Recommendations range from psychoanalysis and exploratory psychotherapy to an explicitly supportive treatment aimed at strengthening adaptive defenses. The authors contend that no single approach is appropriate for all patients in this wide-ranging diagnostic category, which spans a continuum from close-to-neurotic to close-to-psychotic levels of functioning. Careful differentiations based on developmental considerations, ego structures, and relationship patterns provide the basis for the optimal treatment approach.     

Immediate spica cast system for femoral shaft fractures in infants and children

From August 1973 through August 1976, 55 femoral shaft fractures in children were treated by manipulative reduction and immediate application of a double hip spica cast. All had satisfactory results and none had serious complications. Data from the study support our opinion that the immediate spica system is the treatment of choice for these fractures and that traction methods should probably be abandoned as definitive treatment of a femoral shaft fracture in a child.     

Insulin reduces the multiple organ injury and dysfunction caused by coadministration of lipopolysaccharide and peptidoglycan independently of blood glucose: role of glycogen synthase kinase-3beta inhibition

OBJECTIVE: Insulin reduces morbidity and mortality among critically ill patients, but the molecular mechanisms of its effect remain unknown. Insulin is a well-known inhibitor of glycogen synthase kinase-3, which may play an important role in systemic inflammation and shock. Here we investigate the role of blood glucose and glycogen synthase kinase-3beta inhibition in the protective effect of insulin on the organ injury/dysfunction associated with excessive systemic inflammation. DESIGN: Prospective, randomized study. SETTING: University-based research laboratory. SUBJECTS: Eighty-five anesthetized Wistar rats. INTERVENTIONS: Rats received Escherichia coli lipopolysaccharide (1 mg/kg) and Staphylococcus aureus peptidoglycan (0.3 mg/kg) or vehicle intravenously. Insulin (1.4 units/kg intravenously) was administered in the absence or presence of continuous glucose administration (4.5 mg/kg/hr intravenously) either prophylactically or therapeutically. The potent and selective glycogen synthase kinase-3beta inhibitor TDZD-8 (1 mg/kg intravenously) or vehicle (10% dimethyl sulfoxide) was administered either prophylactically or therapeutically. MEASUREMENTS AND MAIN RESULTS: Coadministration of lipopolysaccharide and peptidoglycan resulted in increases in the serum levels of creatinine (indicator of renal dysfunction), alanine aminotransferase, and aspartate aminotransferase (indicators of liver injury) at 6 hrs. Insulin or TDZD-8 similarly attenuated the organ injury/dysfunction caused by lipopolysaccharide and peptidoglycan when given either prophylactically or therapeutically. Continuous glucose administration had no effect on blood glucose levels or organ injury/dysfunction at 6 hrs. Treatment with insulin or TDZD-8 reduced the plasma levels of the proinflammatory cytokine interleukin-1beta. In vitro, insulin or TDZD-8 caused similar reductions in the nuclear factor-kappaB p65 activity and similar increases in the phosphorylation of Ser9 of glycogen synthase kinase-3beta. CONCLUSIONS: Therapy with insulin or the potent and selective glycogen synthase kinase-3beta inhibitor TDZD-8 reduced the organ injury/dysfunction caused by lipopolysaccharide and peptidoglycan in the rat. We propose that the inhibitory effect of insulin on the activity of glycogen synthase kinase-3beta contributes to the protective effect of insulin against the organ injury/dysfunction caused by excessive systemic inflammation independently of any effects on blood glucose.