Evolutionarily conserved prefrontal-amygdalar dysfunction in early-life anxiety.

Some individuals are endowed with a biology that renders them more reactive to novelty and potential threat. When extreme, this anxious temperament (AT) confers elevated risk for the development of anxiety, depression and substance abuse. These disorders are highly prevalent, debilitating and can be challenging to treat. The high-risk AT phenotype is expressed similarly in children and young monkeys and mechanistic work demonstrates that the central (Ce) nucleus of the amygdala is an important substrate. Although it is widely believed that the flow of information across the structural network connecting the Ce nucleus to other brain regions underlies primates' capacity for flexibly regulating anxiety, the functional architecture of this network has remained poorly understood. Here we used functional magnetic resonance imaging (fMRI) in anesthetized young monkeys and quietly resting children with anxiety disorders to identify an evolutionarily conserved pattern of functional connectivity relevant to early-life anxiety. Across primate species and levels of awareness, reduced functional connectivity between the dorsolateral prefrontal cortex, a region thought to play a central role in the control of cognition and emotion, and the Ce nucleus was associated with increased anxiety assessed outside the scanner. Importantly, high-resolution 18-fluorodeoxyglucose positron emission tomography imaging provided evidence that elevated Ce nucleus metabolism statistically mediates the association between prefrontal-amygdalar connectivity and elevated anxiety. These results provide new clues about the brain network underlying extreme early-life anxiety and set the stage for mechanistic work aimed at developing improved interventions for pediatric anxiety.

Pediatric autoimmune neuropsychiatric disorders and streptococcal infections: role of otolaryngologist.

OBJECTIVE: To increase awareness and understanding of the putative role of streptococcal infection in the development of neuropsychiatric disorders in children and to discuss therapeutic options in this group of patients. METHODS: Case illustration and literature review. RESULTS: Two siblings, one with obsessive-compulsive disorder (OCD) and one with a tic disorder, had tonsillectomy for recurrent streptococcal pharyngitis. At the latest follow-up visit (11 mo postoperatively), both patients exhibited significant improvement in their psychiatric illnesses. We discuss these cases as well as the diagnosis, pathophysiology, and treatment of pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS). CONCLUSION: PANDAS is an active area of research investigating the relationship between streptococcal infections and the development of obsessive-compulsive disorder or tic disorders (or both) in children. The etiopathogenesis of PANDAS is thought to reflect autoimmune mechanisms and involvement of the basal ganglia of susceptible hosts. Because otolaryngologists evaluate a large portion of pediatric patients with recurrent streptococcal pharyngitis, it is important to be aware of this association and to manage these patients appropriately.

Internalizing problems of childhood and adolescence: prospects, pitfalls, and progress in understanding the development of anxiety and depression.

The focus of this article is on internalizing problems that are experienced by children and adolescents. We provide an historical perspective, selectively examine the current state of knowledge, consider advances and gaps in what is known, and identify new research directions. Diagnosis, epidemiology, theory, and research first are considered separately for anxiety and depressive disorders. These internalizing problems, however, whether clinical or subclinical, share many common features and show high comorbidity rates. We emphasize the importance of systematic analysis of comorbid anxiety and depression, including their comorbidity with externalizing problems. This could lead to more valid classification of subtypes of internalizing problems and further an understanding of the diverse conditions that constitute internalized distress. We highlight the need to study anxiety and depression within a developmental psychopathology framework, as well as to include both categorical and dimensional assessments of these problems in the same research designs. This will be essential for understanding the complex interplay of biological and environmental processes that contribute to the emergence, progression, and amelioration of internalizing problems over time.

Nucleotides regulate NaCl transport in mIMCD-K2 cells via P2X and P2Y purinergic receptors.

Extracellular nucleotides regulate NaCl transport in some epithelia. However, the effects of nucleotide agonists on NaCl transport in the renal inner medullary collecting duct (IMCD) are not known. The objective of this study was to determine whether ATP and related nucleotides regulate NaCl transport across mouse IMCD cell line (mIMCD-K2) epithelial monolayers and, if so, via what purinergic receptor subtypes. ATP and UTP inhibited Na(+) absorption [measured via Na(+) short-circuit current (I(Na)(sc))] and stimulated Cl(-) secretion [measured via Cl(-) short-circuit current (I(Cl)(sc))]. Using selective P2 agonists, we report that P2X and P2Y purinoceptors regulate I(Na)(sc) and I(Cl)(sc). By RT-PCR, two P2X receptor channels (P2X(3), P2X(4)) and two P2Y G protein-coupled receptors (P2Y(1), P2Y(2)) were identified. Functional localization of P2 purinoceptors suggest that I(Cl)(sc) is stimulated by apical membrane-resident P2Y purinoceptors and P2X receptor channels, whereas I(Na)(sc) is inhibited by apical membrane-resident P2Y purinoceptors and P2X receptor channels. Together, we conclude that nucleotide agonists inhibit I(Na)(sc) across mIMCD-K2 monolayers through interactions with P2X and P2Y purinoceptors expressed on the apical plasma membrane, whereas extracellular nucleotides stimulate I(Cl)(sc) through interactions with P2X and P2Y purinoceptors expressed on the apical plasma membrane.

Patency of 24-gauge peripheral intermittent infusion devices: a comparison of heparin and saline flush solutions.

The purpose of this study was to compare the effectiveness of heparin and normal saline flush solutions in maintaining the patency of 24-gauge peripheral intermittent infusion devices (PIIDs). A prospective, non-randomized, sequential, blinded study design was conducted on a pediatric and a neonatal intensive care unit. The sample consisted of 134 catheters in 61 patients. Heparin and saline flush groups were similar for age, PIID placement site, irritating substances infused, and initial IV function. The median duration of catheters flushed with heparin was 42 hours and with saline was 35.3 hours. Kaplan-Meier Survival Analysis indicated that the duration of catheters flushed with heparin was significantly longer than those flushed with saline (p = .02). More catheters flushed with saline were removed because of problems (p = .027). Results of this study suggest that heparin is more effective than saline in maintaining the patency of small, 24-gauge catheters.

Mothers' perceptions of the quality of their infants' back transfer.

OBJECTIVE: To describe mothers' experiences with back transfer of their infants from a neonatal intensive-care unit (NICU) to a community hospital (CH). DESIGN: Descriptive correlational study. PARTICIPANTS: One hundred forty-three mothers whose infants were back transferred from regional NICUs to 1 of 20 Level I or Level II CHs. MAIN OUTCOME MEASURES: Quality of back transfer was measured by the NICU/CH Transfer Quality Scale developed by the investigators. Overall level of stress related to back transfer was also measured. RESULTS: More positive experiences with the NICU component of back transfer were related to fewer perceived differences in physician practice between NICUs and CH settings and fewer infant problems after transfer (R2 = 8.1%, p = .007). More positive experiences with the CH component of back transfer were related to fewer perceived differences in nursing and medical practices between settings; fewer infant problems after transfer; and more sources of pretransfer preparation (R2 = 33.4%, p < .0001). Lower levels of overall stress associated with transfer were related to fewer infant problems after transfer and greater lengths of stay in the NICU (R2 = 8.8%, p = .01). CONCLUSION: Results support the need for consistency of care and coordinated approaches to back transfer.

Hyperosmolality inhibits sodium absorption and chloride secretion in mIMCD-K2 cells.

Previously we demonstrated that a cell line derived from mouse inner medullary collecting duct (mIMCD-K2) absorbs Na+ and secretes Cl- by electrogenic mechanisms and that arginine vasopressin (AVP) stimulates Cl- secretion. The objective of the present study was to determine whether hyperosmolality, both acute (minutes) and chronic (weeks), affects electrogenic Na+ absorption IscNa and electrogenic Cl- secretion IscCl across the IMCD. To this end, we measured IscNa and IscCl across monolayers of mIMCD-K2 cells mounted in Ussing-type chambers. Osmolality was increased from 290 to 590 mosmol/kgH2O by adding 200 mosmol/kgH2O of NaCl and 100 mosmol/kgH2O of urea or 300 mosmol/kgH2O of sucrose to the bathing solutions. Acute and chronic hyperosmolality reduced basal IscNa and IscCl and the AVP-stimulated rise in IscCl. These findings indicate that osmolality is an important determinant of IscNa and IscCl across IMCD cells and that the osmolality of the interstitial fluid should be considered when evaluating the effects of hormones and other factors on Na+ and Cl- transport by the IMCD.

Mothers' perceptions of the quality of their infants' back transfer: pilot study results.

This pilot study was designed to test an instrument measuring mothers' perceptions of the quality of the back-transfer experience from a neonatal intensive care unit in a tertiary medical center to a community hospital. Forty-one mothers completed a questionnaire that contained the 24-item NICU/Community Hospital Transfer Quality Scale, a 1-item measure of stress associated with the overall experience, and other variables that might affect the transfer experience. Transfer quality was strongly correlated with the overall stress of the transfer (r = .61, p < .001). That is, the higher the perceived transfer quality, the less stress the mother associated with the transfer. This instrument had a test-retest reliability of r = .82 (p < .001, n = 23) and a Chronbach's alpha of .84. Comments made by mothers indicated that communication with health care providers is a very important but sometimes inadequately addressed component of the transfer experience. Nurses can play a key role in facilitating communication between the family and health care providers in both the tertiary and community settings. Four goals for enhancing communication between parents and health care providers are described.

Leukocyte adhesion molecules as a cofactor in AIDS: basic science and pilot study.

It is well known that the AIDS pandemic is a consequence of pandemic HIV infection. However, Koch's postulates are not satisfied for two reasons: 1) AIDS cannot be experimentally produced in animals susceptible to HIV infection and 2) some people have AIDS (idiopathic CD4+ T lymphocytopenia) in the absence of HIV infection. It follows that there is a human immunologic cofactor (HIC) that causes AIDS when certain other conditions are satisfied, and the most common of these other conditions (but not the only one) is HIV infection. Results from microbiology make leukocyte adhesion molecules a good candidate for the HIC. We have tested this hypothesis with a pilot study in which a small number of patients with HIV disease were infused with a monoclonal mouse antibody (MmAb) directed against an LFA-1 adhesion epitope, and then with F(ab) and F(ab)2' fragments that bind to the same epitope but are nonimmunogenic. Both agents reduced peripheral viral burden significantly but fragments were more effective in this respect than the MmAb due to the mitogenic properties of the latter. For the same reason, only the MmAb were highly effective in raising circulating levels of single and double-marked CD4+ T lymphocytes, with a correlated resolution of cutaneous anergy.

The Fremantle Lead Study.

OBJECTIVE: To ascertain blood lead levels in a sample of preschool children from Framantle, Western Australia, and to correlate these with possible risk factors. METHODOLOGY: The study was a cross-sectional prevalence survey of 120 children from day-care centres and 44 hospital inpatients. Blood lead and ferritin levels were determined and a risk factor questionnaire was completed by parents. RESULTS: Of the 164 children 25.6% had lead levels above the NH&MRC goal (< 10 micrograms/dL). Nine of 133 (6.7%) had ferritin levels below 10 micrograms/L suggesting iron deficiency. Excessive blood lead concentrations as defined by the NH & MRC (> 9 micrograms/dL) related to: child's presence during house renovation (OR 3.35, P = 0.007, 95% CI 1.39-8.81); Aboriginality (OR 6.4, P = 0.008, 95% CI 1.6-24.9), and, in the 9-24 month age group, inversely to distance between home and a road carrying > 7000 vehicles/day (r -0.56, P = 0.009, n = 24). CONCLUSIONS: A group of Fremantle children with unacceptably high blood lead levels has been identified. Renovation of older housing and Aboriginality are important risk factors.

Confused patients in the acute care setting: prevalence, interventions, and outcomes.

1. A descriptive design was used to measure nurses' assessment of the prevalence of patients who are confused, the interventions used, and these patients' outcomes on three nursing units in an acute care setting. 2. Confused patients had less favorable outcomes at discharge than did the group of nonconfused patients. 3. Of the three interventions that were monitored, confused patients were more likely to have either restraints or medications than to have a sitter (a sitter was either a paid staff member or a family member who monitored the patient directly).