Correlation between Multiparametric MR Imaging and Molecular Genetics in Pontine Pediatric High-Grade Glioma.

BACKGROUND AND PURPOSE: Molecular profiling is a crucial feature in the "integrated diagnosis" of CNS tumors. We aimed to determine whether radiomics could distinguish molecular types of pontine pediatric high-grade gliomas that have similar/overlapping phenotypes on conventional anatomic MR images. MATERIALS AND METHODS: Baseline MR images from children with pontine pediatric high-grade gliomas were analyzed. Retrospective imaging studies included standard precontrast and postcontrast sequences and DTI. Imaging analyses included median, mean, mode, skewness, and kurtosis of the ADC histogram of the tumor volume based on T2 FLAIR and enhancement at baseline. Histone H3 mutations were identified through immunohistochemistry and/or Sanger or next-generation DNA sequencing. The log-rank test identified imaging factors prognostic of survival from the time of diagnosis. Wilcoxon rank-sum and Fisher exact tests compared imaging predictors among groups. RESULTS: Eighty-three patients had pretreatment MR imaging and evaluable tissue sampling. The median age was 6 years (range, 0.7-17 years); 50 tumors had a K27M mutation in H3-3A, and 11, in H3C2/3. Seven tumors had histone H3 K27 alteration, but the specific gene was unknown. Fifteen were H3 wild-type. Overall survival was significantly higher in H3C2/3- compared with H3-3A-mutant tumors (P = .003) and in wild-type tumors compared with any histone mutation (P = .001). Lower overall survival was observed in patients with enhancing tumors (P = .02) compared with those without enhancement. H3C2/3-mutant tumors showed higher mean, median, and mode ADC_total values (P < .001) and ADC_enhancement (P < .004), with lower ADC_total skewness and kurtosis (P < .003) relative to H3-3A-mutant tumors. CONCLUSIONS: ADC histogram parameters are correlated with histone H3 mutation status in pontine pediatric high-grade glioma.

MR Imaging Correlates for Molecular and Mutational Analyses in Children with Diffuse Intrinsic Pontine Glioma.

BACKGROUND AND PURPOSE: Recent advances in molecular techniques have characterized distinct subtypes of diffuse intrinsic pontine gliomas. Our aim was the identification of MR imaging correlates of these subtypes. MATERIALS AND METHODS: Initial MRIs from subjects with diffuse intrinsic pontine gliomas recruited for a prospective clinical trial before treatment were analyzed. Retrospective imaging analyses included FLAIR/T2 tumor volume, tumor volume enhancing, the presence of cyst and/or necrosis, median, mean, mode, skewness, kurtosis of ADC tumor volume based on FLAIR, and enhancement at baseline. Molecular subgroups based on EGFR and MGMT mutations were established. Histone mutations were also determined (H3F3A, HIST1H3B, HIST1H3C). Univariate Cox proportional hazards regression was used to test the association of imaging predictors with overall and progression-free survival. Wilcoxon rank sum, Kruskal-Wallis, and Fisher exact tests were used to compare imaging measures among groups. RESULTS: Fifty patients had biopsy and MR imaging. The median age at trial registration was 6 years (range, 3.3-17.5 years); 52% were female. On the basis of immunohistochemical results, 48 patients were assigned to 1 of 4 subgroups: 28 in MGMT-/epidermal growth factor receptor (EGFR)-, 14 in MGMT-/EGFR+, 3 in MGMT+/EGFR-, and 3 in MGMT+/EGFR+. Twenty-three patients had histone mutations in H3F3A, 8 in HIST1H3B, and 3 in HIST1H3C. Enhancing tumor volume was near-significantly different across molecular subgroups (P = .04), after accounting for the false discovery rate. Tumor volume enhancing, median, mode, skewness, and kurtosis ADC T2-FLAIR/T2 were significantly different (P ≤ .048) between patients with H3F3A and HIST1H3B/C mutations. CONCLUSIONS: MR imaging features including enhancement and ADC histogram parameters are correlated with molecular subgroups and mutations in children with diffuse intrinsic pontine gliomas.

Translational Pharmacokinetic-Pharmacodynamic Modeling and Simulation: Optimizing 5-Fluorouracil Dosing in Children With Pediatric Ependymoma.

We previously investigated novel therapies for pediatric ependymoma and found 5-fluorouracil (5-FU) i.v. bolus increased survival in a representative mouse model. However, without a quantitative framework to derive clinical dosing recommendations, we devised a translational pharmacokinetic-pharmacodynamic (PK-PD) modeling and simulation approach. Results from our preclinical PK-PD model suggested tumor concentrations exceeded the 1-hour target exposure (in vitro IC90), leading to tumor growth delay and increased survival. Using an adult population PK model, we scaled our preclinical PK-PD model to children. To select a 5-FU dosage for our clinical trial in children with ependymoma, we simulated various 5-FU dosages for tumor exposures and tumor growth inhibition, as well as considering tolerability to bolus 5-FU administration. We developed a pediatric population PK model of bolus 5-FU and simulated tumor exposures for our patients. Simulations for tumor concentrations indicated that all patients would be above the 1-hour target exposure for antitumor effect.

Metaraminol (Aramine) in the management of a significant amlodipine overdose.

OBJECTIVE: To report a patient with a significant amlodipine self-poisoning who failed to clinically respond to conventional treatment and was managed with metaraminol (Aramine). PATIENT: A 43-year old male presenting after ingestion of 560 mg amlodipine, who failed to respond clinically to treatment with fluid resuscitation, calcium salts, glucagon and norepinephrine/epinephrine inotropic support. MAIN RESULTS: Following a loading bolus of 2 mg and intravenous infusion (83 microg/min) of metaraminol (Aramine) there was improvement in his blood pressure, cardiac output and urine output. CONCLUSIONS: This is the first case report of the beneficial use of metaraminol (aramine) in the management of significant amlodipine poisoning unresponsive to conventional therapy.

Factorial validity of the short-form McGill pain questionnaire (SF-MPQ).

Although widely used, there have been few investigations of the factorial validity of the short-form McGill Pain Questionnaire (SF-MPQ; Melzack, 1987). Confirmatory factor analysis was performed on item responses to the SF-MPQ obtained from 188 patients with chronic back pain. Consistent with the original structure proposed by Melzack (1987), results indicated that the SF-MPQ is best represented by a two-factor solution. However, these findings are contrary to results obtained by Burckhardt and Bjelle (1994) who, using their Swedish version of the SF-MPQ, obtained a three-factor solution. Potential explanations for the disparity between the results of the two studies are explored and recommendations for continuing clinical and research applications are offered.

Factorial validity of the Childhood Trauma Questionnaire in men and women.

In an effort to confirm the factorial validity of the Childhood Trauma Questionnaire (CTQ) across sex, the items from the CTQ for 916 university students were subjected to confirmatory factor analysis. Results indicated that the factor structure for the CTQ was significantly different for men and women. For women, the items from the Physical Abuse subscale did not create a stable factor and thus appear not to be conceptually valid. Conversely, for men, the five-factor model provided a relatively good fit to the data. This investigation provides important information regarding sex differences in the factorial validity of the CTQ. Implications and future research directions are discussed.

Anxiety sensitivity and other emotionality traits in predicting headache medication use in patients with recurring headaches: implications for abuse and dependency.

The objective of the present investigation was to clarify the role that anxiety sensitivity (AS) and other related constructs play in headache medication use in patients with recurring headaches. A total of 108 patients (88% female) with chronic recurring headaches (mean duration = 205.6 months) provided complete responses to a self-report inventory administered during a treatment visit to an outpatient neurology clinic. The inventory included measures of depression, trait anger, trait anxiety, fear of pain, AS, and the impact of headache on daily living. AS and fear of pain were used in accordance with their multidimensional conceptualizations. Hierarchical multiple regression analyses were conducted to determine the variables that contributed significantly to the prediction of current over-the-counter analgesic and prescription medication use. After controlling for pain severity, the cognitive anxiety dimension of fear of pain was the only significant predictor of over-the-counter analgesic use. For prescription medication use, the fear of physical catastrophe dimension of AS and the physiological anxiety dimension of fear of pain were significant predictors, although the predictive direction of the former was opposite to that found in prior studies. The models, while significant, accounted for relatively small amounts of variance. Implications of these results and issues of medication abuse and dependency are discussed.

Bile duct injury during laparoscopic cholecystectomy without operative cholangiography.

BACKGROUND: The role of operative cholangiography in the prevention of bile duct injuries is controversial. A prospective audit of biliary injury is presented. METHODS: Laparoscopic cholecystectomy without operative cholangiography was undertaken in a consecutive series of 1200 patients. All biliary injuries were recorded. RESULTS: Meticulous dissection proved to be a reliable safeguard against injury to the right hepatic, common hepatic and common bile ducts. However, four accessory ducts were sacrificed and localized injury to the common hepatic or common bile duct occurred in three patients. These injuries would not have been prevented by operative cholangiography. CONCLUSION: Operative cholangiography is not a prerequisite for the safe performance of laparoscopic cholecystectomy and cannot be relied upon to prevent all biliary injuries.

Neuro-optometric facilitation of vision recovery after acquired brain injury.

Visual field loss following brain injury often impairs the individual's rehabilitation, function and safety. Such impairments prevent individuals from returning to productive lifestyles. A previous article documents outcomes that measure increased awareness for patients suffering visual field loss. This research investigates and reports on increasing visual recovery, as well as functional and emotional rehabilitation outcomes, using the Visual Field Awareness System™ and treatment strategies. The three case studies represent issues including age, visual field loss, vision recovery as a dynamic process, and functional outcome measures. Measures of increased awareness, recovery of vision, relative visual field sensitivity, continued recovery even after completion of treatment, and improved emotional status with gained independence were among the positive outcome results of this research.

A temporary solution to reverse staging: the skin care evaluation sheet.

The National Pressure Ulcer Advisory Panel (NPUAP) has published recommendations over the last several years against the use of reverse staging to describe the healing of a pressure ulcer. Clinical studies have shown that as Stage IV pressure ulcers heal to more shallow depths, they do not replace lost muscle, subcutaneous fat, and dermis before they re-epithelialize. Instead the defect is filled with granulation tissue composed of endothelial cells, fibroblasts, collagen, and an extracellular matrix. The Minimum Data Set-2 (MDS-2) is a comprehensive assessment tool required to be completed on a quarterly basis in all long term care facilities that provide care to Medicare patients. Section M of the MDS-2 addresses skin condition and requires that pressure ulcers be staged as assessed within seven days of documentation, using the guidelines in that section. No mechanism currently exists to document progression of ulcer healing, leaving the practitioner no alternative but to restage the ulcer. This article presents one facility's effort to acknowledge the NPUAP recommendations, while complying with reimbursement screening methods.

'Efficient' timely evacuation of intracranial haematoma--the effect of transport direct to a specialist centre.

Patients with intracranial haematoma following head injury may have little primary brain injury, but sustain a secondary brain injury that can often be minimized by early evacuation of the haematoma. Rapid intervention by a neurosurgeon with early evacuation of the haematoma gives a better outcome. The timing of treatment in 403 patients with severe head injuries, admitted to the Royal London Hospital between January 1991 and December 1994 was examined. All cases had been transported directly from the accident scene by the Helicopter Emergency Medical Service because the local hospital did not have neurosurgical facilities. The median time to medical intervention was 15 min (95 per cent, confidence interval (CI) 14-16) and the median time to neurosurgery was 177 min (95 per cent, CI 171-195). As secondary interhospital transfer of patients with head injuries is known to increase the time to neurosurgical intervention and is a time of great risk of secondary insult to the brain, transfer direct from the scene of the accident to an appropriate centre allows a process of care that has been shown to be associated with a better outcome.

Measuring codependents' close relationships: a preliminary study.

A survey of clinical literature and input from addiction counselors yielded eight commonly assumed characteristics of codependents' relationships. These were defined in a manner amenable to measurement by the Acquaintance Description Form (Wright, 1985), and added to the standard form to provide a codependent version (ADF-C2). Forty-one women and 19 men awaiting or beginning codependent counseling responded to the ADF-C2, and to Friel's Codependency Assessment Inventory and forms soliciting background information. Thirty-nine women and 30 men from the general population provided a comparison group. Although tentative, results were encouraging concerning progress toward measuring codependents' relationships. Broad profiles for both women and men supported the foundational observation that codependents maintain strong commitments to their partners notwithstanding stress and unrewardingness. Specifically, codependent women showed five expected characteristics: Control, Exaggerated Responsibility, Worth Dependency, Rescue Orientation, and Change Orientation. Codependent men showed two: Control and Exaggerated Responsibility.

Strain and sex variation in the susceptibility to streptococcal cell wall-induced polyarthritis in the rat.

Sixteen inbred rat strains were examined for susceptibility and resistance to group A streptococcal cell wall-induced polyarthritis. The findings indicated that 2 or more genetic loci, as well as sex-related factors, played a major role in determining susceptibility to arthritis in this model. Breeding studies demonstrated that susceptibility was a dominant or codominant trait. A positive association between the severity of arthritis and the development of chronic inflammation in multiple tissues was also observed. In strains that were relatively resistant to arthritis, chronic inflammation was generally limited to the spleen. Since translocation of the poorly degradable and phlogogenic streptococcal cell walls to the synovium and other tissues appears to initiate inflammation, these studies suggested that susceptibility might be the result of a defect in host mechanisms limiting cell wall dissemination.

The relationship of wives' treatment to the drinking status of alcoholics.

When an alcoholic's wife is active in Al-Anon, participates in her husband's inpatient treatment or postreatment counseling or receives several types of treatment, her husband is more likely to be abstinent.