Regional Differences in Gamma-Aminobutyric Acid and Glutamate Concentrations in the Healthy Newborn Brain.

BACKGROUND AND PURPOSE: Gamma-aminobutyric acid and glutamate system disruptions may underlie neonatal brain injury. However, in vivo investigations are challenged by the need for special 1H-MR spectroscopy sequences for the reliable measurement of the neurotransmitters in this population. We used J-edited 1H-MR spectroscopy (Mescher-Garwood point-resolved spectroscopy) to quantify regional in vivo gamma-aminobutyric acid and glutamate concentrations during the early postnatal period in healthy neonates. MATERIALS AND METHODS: We prospectively enrolled healthy neonates and acquired Mescher-Garwood point-resolved spectroscopy spectra on a 3T MR imaging scanner from voxels located in the cerebellum, the right basal ganglia, and the right frontal lobe. CSF-corrected metabolite concentrations were compared for regional variations and cross-sectional temporal trends with advancing age. RESULTS: Fifty-eight neonates with acceptable spectra acquired at postmenstrual age of 39.1 (SD, 1.3) weeks were included for analysis. Gamma-aminobutyric acid (+ macromolecule) (2.56 [SD, 0.1]) i.u., glutamate (3.80 [SD, 0.2]), Cho, and mIns concentrations were highest in the cerebellum, whereas NAA (6.72 [SD, 0.2]), NAA/Cho, Cr/Cho, and Glx/Cho were highest in the basal ganglia. Frontal gamma-aminobutyric acid (1.63 [SD, 0.1]), Glx (4.33 [SD, 0.3]), Cr (3.64 [SD, 0.2]), and Cho concentrations were the lowest among the ROIs. Glx, NAA, and Cr demonstrated a significant adjusted increase with postmenstrual age (ß = 0.2-0.35), whereas gamma-aminobutyric acid and Cho did not. CONCLUSIONS: We report normative regional variations and temporal trends of in vivo gamma-aminobutyric acid and glutamate concentrations reflecting the functional and maturational status of 3 distinct brain regions of the neonate. These measures will serve as important normative values to allow early detection of subtle neurometabolic alterations in high-risk neonates.

Utility of post-traumatic amnesia in predicting 1-year productivity following traumatic brain injury: comparison of the Russell and Mississippi PTA classification intervals.

BACKGROUND: Duration of post-traumatic amnesia (PTA) correlates with global outcomes and functional disability. Russell proposed the use of PTA duration intervals as an index for classification of traumatic brain injury (TBI) severity. Alternative duration-based schemata have been recently proposed as better predictors of outcome to the commonly cited Russell intervals. OBJECTIVE: Validate a TBI severity classification model (Mississippi intervals) of PTA duration anchored to late productivity outcome, and compare sensitivity against the Russell intervals. METHODS: Prospective observational data on TBI Model System participants (n=3846) with known or imputed PTA duration during acute hospitalisation. Productivity status at 1-year postinjury was used to compare predicted outcomes using the Mississippi and Russell classification intervals. Logistic regression model-generated curves were used to compare the performance of the classification intervals by assessing the area under the curve (AUC); the highest AUC represented the best-performing model. RESULTS: All severity variables evaluated were individually associated with return to productivity at 1 year (RTP1). Age was significantly associated with RTP1; however, younger patients had a different association than older patients. After adjustment for individually significant variables, the odds of RTP1 decrease by 14% with every additional week of PTA duration (95% CI 12% to 17%; p<0.0001). The AUC for the Russell intervals was significantly smaller than the Mississippi intervals. CONCLUSIONS: PTA duration is an important predictor of late productivity outcome after TBI. The Mississippi PTA interval classification model is a valid predictor of productivity at 1 year postinjury and provides a more sensitive categorisation of PTA values than the Russell intervals.

Pulmonary hypertension in patients with bronchiolitis obliterans syndrome listed for retransplantation.

Bronchiolitis Obliterans Syndrome (BOS) is a major cause of morbidity and mortality post-lung transplantation. Pulmonary hypertension (PH) may complicate the course of patients with advanced lung disease. We sought to characterize the prevalence of PH in patients with BOS. We performed a retrospective analysis of lung transplant recipients with BOS relisted for transplantation with the United Network for Organ Sharing (UNOS). Right heart catheterization (RHC) data were required for analysis. Eighty patients with BOS qualified for the analysis. PH was present in 32.5% of patients with an average mean pulmonary artery pressure (mPAP) of 32.3 mmHg (range: 26-63 mmHg). Of these, 42.3% had an elevated pulmonary capillary wedge pressure. There was no difference in PH prevalence between bilateral (26.5%) and single lung recipients (41.9%), nor did it differ by primary disease. There was no correlation between pulmonary function data and the presence or severity of PH. There was no difference in oxygen requirements or 6-min walk distance between patients with and without PH. This is the first report of PH in patients with BOS. Many of these cases occur in association with diastolic dysfunction. Although no impact on functional status or outcomes was discerned, further studies appear warranted.

Social anxiety disorder in review: two decades of progress.

Social anxiety disorder (SAD) is among the most common of all psychiatric disorders. It presents with a lifetime prevalence rate of up to 16% in the general population and, like other anxiety disorders, is more frequent in women. Patients with SAD suffer from considerable psychiatric comorbidity that is often preceded by social anxiety. Social anxiety affects people early in life and provokes a great deal of impairment and cost, much being related to the under-recognition and/or under-treatment of this disorder, which occurs frequently with GPs and others specialists. There is a clear need among GPs for training and awareness about the existence of this disorder, its assessment, differential diagnosis and available treatments. In this paper we review the development of the concept of SAD and its epidemiology, and discuss the available information regarding cost and how SAD presents in primary-care settings. Potential aetiologies and studies concerning possible neurobiological mechanisms are also reviewed. Pharmacological and psychosocial treatments for SAD are examined and effect sizes calculated for placebo-controlled pharmacological studies of five medication categories.

Incidence of recurrent diagnoses of Chlamydia trachomatis genital infections among male and female soldiers of the US Army.

BACKGROUND/OBJECTIVES: Few studies of Chlamydia trachomatis incidence, especially among men, and most studies of C. trachomatis in US military populations are cross sectional prevalence surveys. A population based retrospective cohort was used to determine risk factors for repeat diagnoses of genital C. trachomatis infections among male and female soldiers with previous C. trachomatis infections. METHODS: All active duty soldiers diagnosed with C. trachomatis genital infections between 1994 and 1998. Cohort members were passively followed until repeat diagnoses of C. trachomatis infection, termination of army service, or the end of the study. RESULTS: Among 11,771 soldiers with initial diagnoses of chlamydia, the crude rate of repeat diagnoses was 52.0 per 1000 person years. Women and men aged 20-24 were at greatest unadjusted risk of reinfection. After adjustment, women aged 20-24 and men aged 25-29 were at higher risk than their younger or older counterparts. CONCLUSIONS: Results of this study suggest that both male and female soldiers who are diagnosed with chlamydia infections have relatively high risks of reinfection through their 20s.

The self-assessment of resilience and anxiety: psychometric properties.

This report describes the psychometric properties of the Self-Assessment of Resilience and Anxiety (SARA) scale within the context of a study of kava for generalized anxiety. This eight-item, patient-rated scale includes questions designed to measure calmness, mental clarity, confidence, physical well being, sociability, and resilience. The SARA scale was administered during a clinical trial of kava versus placebo in 38 subjects diagnosed with generalized anxiety disorder (GAD). Validation of the SARA scale was assessed against the Hamilton Rating Scale for Anxiety, Hospital Anxiety and Depression Scale, Penn State Worry Questionnaire, Sheehan Disability Scale, Arizona Sexual Experience scale, and Clinical Global Impression of Illness Improvement scale. Good test-retest reliability, internal consistency, convergent validity, and sensitivity to treatment were identified, and factor analyses revealed a three-factor internal structure. The SARA scale was responsive to symptom change over time and correlated with comparable GAD symptom measures. The SARA scale demonstrates solid psychometric properties and may serve as a reliable and valid measure in the use of kava or related medicinal herbs.

Inappropriate medication prescribing in homebound older adults.

OBJECTIVES: Little is known about the prescribing of medications in the growing population of homebound older adults. We report on the prevalence and pattern of inappropriate medications in a nursing home-eligible, homebound population. DESIGN: A cross-sectional design. SETTING: A managed care plan for individuals meeting nursing home eligibility. PARTICIPANTS: 2193 homebound people older than age 60. MEASUREMENTS: We reviewed the pharmacy profiles of all older homebound enrollees. We identified the average number of medications per patient and the most commonly prescribed classes of drugs. The medication profiles were also analyzed in the context of the 26 drugs/groups listed as inappropriate by the explicit criteria of Beers [Arch Intern Med 1997; 157:1531-1536]. RESULTS: A total of 2193 people aged 60 to 106 (mean 82.8 +/- 8.8) were taking an average of 5.3 +/- 2.9 drugs (range 0-22). Cardiac drugs and benzodiazepines were the medications most commonly prescribed. We found 1152 of the total 11,689 prescriptions (9.9%) to be inappropriate. Eight hundred seventy-one (39.7%) of these 2193 residents had at least one inappropriate prescription, and 230 (10.4%) had two or more. Of particular concern were 285 people prescribed excessive doses of temazepam and zoldipem, 211 people taking first-generation antihistamines, 115 taking doxepin or amitriptyline, 106 taking an ergoloid, 98 taking dipyridamole, and 85 prescribed a long-acting benzodiazepine. CONCLUSIONS: Our study revealed a high prevalence of psychotropic medications and inappropriate drug use among older homebound residents, a group that is at the highest risk for adverse drug reactions. Because this group is not subject to oversight by regulatory agencies, further interventional studies and provider education will be important.

Tropylium tetrafluoroborate, a novel substrate for aldehyde oxidase.

The stabilized carbonium ion salt, tropylium tetrafluoroborate, was oxidized to tropone (cycloheptatrienone) by rabbit liver aldehyde oxidase but not by the closely related molybdenum hydroxylase, xanthine oxidase. The tropylium cation is an aromatic hydrocarbon which lacks the aldehyde, imine, or iminium functional groups present in other substrates of aldehyde oxidase. The unique structural features of the tropylium ion should make it a useful tool for mechanistic studies of aldehyde oxidase.