[Visual disturbances and headaches in children].
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Adolescent↗
Biomedical subjects
D Holland
Publications and source records attributed to D Holland.
Subversion of the T/B lineage decision in the thymus by lunatic fringe-mediated inhibition of Notch-1.
Notch-1 signaling is essential for lymphoid progenitors to undergo T cell commitment, but the mechanism has not been defined. Here we show that thymocytes ectopically expressing Lunatic Fringe, a modifier of Notch-1 signaling, induce lymphoid progenitors to develop into B cells in the thymus. This cell fate switch resulted from Lunatic Fringe-mediated inhibition of Notch-1 function, as revealed by experiments utilizing lymphoid progenitors in which Notch-1 activity was genetically manipulated. These data identify Lunatic Fringe as a potent regulator of Notch-1 during the T/B lineage decision and show that an important function of Notch-1 in T cell commitment is to suppress B cell development in the thymus.
Animals↗
An emergency department-based randomized trial of nonbronchoscopic bronchoalveolar lavage for early pathogen identification in severe community-acquired pneumonia.
STUDY OBJECTIVES: Many patients with community-acquired pneumonia are treated empirically without an aggressive search for causative pathogens, an approach adopted largely because of the costs and difficulties encountered during efforts to identify the causative organisms. Blood and sputum cultures are not sensitive, and the more invasive techniques of bronchoscopy and lung biopsy are generally time consuming and not cost-effective. The technique of nonbronchoscopic bronchoalveolar lavage (BAL) has been shown to accurately diagnose the causes of nosocomial pneumonia. The purpose of this study was to determine whether an emergency department-based BAL protocol would lead to more frequent isolation of pneumonia pathogens and result in more changes to tailored antibiotic therapy in comparison with standard care. METHODS: We studied all adult patients admitted with a diagnosis of pneumonia who were tracheally intubated and who had obtainable familial consent in the ED of an urban county hospital from March 1998 to October 1999. Exclusions included antibiotic use within the past 5 days, pneumothorax, hemoptysis, or persistent hypoxia using 100% oxygen. Patients were randomized to standard care versus standard care plus BAL. Blood culture specimens were drawn from all patients before the initiation of antibiotics. All other diagnostic tests were ordered at the discretion of treating physicians. BAL fluid, sputum, and blood culture specimens were tracked, and patient antibiotic course was followed to assess any change in regimen. RESULTS: Twenty-six of 64 patients evaluated for study participation met all eligibility criteria; 14 patients received standard care, and 12 patients received standard care plus BAL. Pneumonia pathogens were identified in 10 (83.3%) of 12 patients in the BAL group and in 4 (28.6%) of 14 patients in the standard care group (P =.007). Comparing BAL versus non-BAL groups, there was no significant difference in the likelihood of overall antibiotic regimen changes (P =.149), but there was a difference with regard to antibiotic changes made in patients with positive culture test results (P =.026). No major complications occurred with BAL catheterizations. CONCLUSION: ED-based BAL catheterization allows for early identification of pathogens in severe community-acquired pneumonia, which leads to changes in antibiotic therapy.
Adult↗
Fluvoxamine for children and adolescents with obsessive-compulsive disorder: a randomized, controlled, multicenter trial.
OBJECTIVE: To determine the safety and efficacy of fluvoxamine for the treatment of children and adolescents with obsessive-compulsive disorder (OCD) with a double-blind, placebo-controlled, multicenter study. METHOD: Subjects, aged 8 to 17 years, meeting DSM-III-R criteria for OCD were recruited from July 1991 to August 1994. After a 7- to 14-day single-blind, placebo washout/screening period, subjects were randomly assigned to fluvoxamine 50 to 200 mg/day or placebo for 10 weeks. Subjects who had not responded after 6 weeks could discontinue the double-blind phase of the study and enter a long-term, open-label trial of fluvoxamine. Analyses used an intent-to-treat sample with a last-observation-carried-forward method. RESULTS: Mean Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS) scores with fluvoxamine were significantly (p < .05) different from those with placebo at weeks 1, 2, 3, 4, 6, and 10. Significant (p < .05) differences between fluvoxamine and placebo were observed for all secondary outcome measures at all visits. Based on a 25% reduction of CY-BOCS scores, 42% of subjects taking fluvoxamine were responders compared with 26% taking placebo. Forty-six (19 fluvoxamine, 27 placebo) of 120 randomized subjects discontinued early. Adverse events with a placebo-adjusted rate greater than 10% were insomnia and asthenia. CONCLUSIONS: Fluvoxamine has a rapid onset of action and is well tolerated and efficacious for the short-term treatment of pediatric OCD.
Adolescent↗
Pharmacokinetics of nelfinavir in human immunodeficiency virus-infected infants.
BACKGROUND: Nelfinavir dosed at approximately 20 to 30 mg/kg three times a day (TID) in older children provides exposure similar to 750 mg TID in adults. However, the pharmacokinetics (PK) of nelfinavir in infants who are < 2 years of age is not well-described. The objective of this study was to determine the pharmacokinetics of nelfinavir in infants < 2 years of age. METHODS: Nelfinavir concentrations were evaluated in 22 HIV-infected infants between 15 days and 2 years of age receiving nelfinavir as part of Pediatric ACTG Study 356. Nelfinavir therapy was initiated at approximately 25 mg/kg TID (n = 18) or approximately 55 mg/kg twice a day (n = 4) and given in combination with nevirapine, stavudine and lamivudine. PK samples were obtained predose and 1.5 and 4 h postdose at approximately 6-month intervals. Eight infants (all < or = 3 months of age) also had intensive PK samples collected at Week 1. RESULTS: The median apparent clearance in the infants with intensive pharmacokinetic sampling was 2.7 liters/h/kg (range, 1.8 to > or = 10) and was similar between twice a day and TID dosing cohorts. Overall nelfinavir concentrations at all collection times were lower in these infants than previously reported in older pediatric patients. CONCLUSIONS: Nelfinavir concentrations in infants are highly variable and lower than those seen in adult or older pediatric populations receiving labeled dosing. Therefore it is necessary to further evaluate nelfinavir safety, effectiveness and pharmacokinetics at higher doses than used among other pediatric populations.
Anti-HIV Agents↗
The efficacy of a universal school-based program to prevent adolescent depression.
Evaluated whether a universal school-based program, designed to prevent depression in adolescents, could be effectively implemented within the constraints of the school environment. Participants were 260 Year 9 secondary school students. Students completed measures of depressive symptoms and hopelessness and were then assigned to 1 of 3 groups: (a) Resourceful Adolescent Program-Adolescents (RAP-A), an 11-session school-based resilience building program, as part of the school curriculum; (b) Resourceful Adolescent Program-Family (RAP-F), the same program as in RAP-A, but in which each student's parents were also invited to participate in a 3-session parent program; and (c) Adolescent Watch, a comparison group in which adolescents simply completed the measures. The program was implemented with a high recruitment (88%), low attrition rate (5.8%), and satisfactory adherence to program protocol. Adolescents in either of the RAP programs reported significantly lower levels of depressive symptomatology and hopelessness at post-intervention and 10-month follow-up, compared with those in the comparison group. Adolescents also reported high satisfaction with the program. The study provides evidence for the efficacy of a school-based universal program designed to prevent depression in adolescence.
Adolescent↗
Competitive hybridization: theory and application in isolation and quantification of differentially regulated genes.
Competitive hybridization is a simple yet powerful method that was developed to screen cDNA libraries for differentially regulated genes. The method is based on competition between unlabeled cDNA from the mRNA of one sample and labeled cDNA from another sample. By manipulating the amount of competing unlabeled cDNA, background signals from the nonregulated genes can be increased or reduced, enabling the signals from differentially regulated genes to be contrasted and to be identified in a quantitative manner. To demonstrate the feasibility of the method, we screened a citrus cDNA library for ethylene-induced genes and identified three genes with different levels of ethylene induction. The mathematical basis of the method and its possible application in gene chip technology are discussed.
Blotting, Northern↗
Persisting diplopia after bilateral laser in situ keratomileusis.
We present a case of persisting diplopia after bilateral laser in situ keratomileusis in a patient with high anisometropia and amblyopia. Treatment of this complication by ocular-muscle surgery was not possible because of missing fusion. We suggest that, especially in cases with anisometropia, a complete examination of binocularity be performed before refractive surgery.
Cornea↗
An observation of the effect of sertraline on breast milk supply.
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Depression, Postpartum↗
A comparative analysis of the plant cellulose synthase (CesA) gene family.
CesA genes are believed to encode the catalytic subunit of cellulose synthase. Identification of nine distinct CesA cDNAs from maize (Zea mays) has allowed us to initiate comparative studies with homologs from Arabidopsis and other plant species. Mapping studies show that closely related CesA genes are not clustered but are found at different chromosomal locations in both Arabidopsis and maize. Furthermore, sequence comparisons among the CesA-deduced proteins show that these cluster in groups wherein orthologs are often more similar than paralogs, indicating that different subclasses evolved prior to the divergence of the monocot and dicot lineages. Studies using reverse transcriptase polymerase chain reaction with gene-specific primers for six of the nine maize genes indicate that all genes are expressed to at least some level in all of the organs examined. However, when expression patterns for a few selected genes from maize and Arabidopsis were analyzed in more detail, they were found to be expressed in unique cell types engaged in either primary or secondary wall synthesis. These studies also indicate that amino acid sequence comparisons, at least in some cases, may have value for prediction of such patterns of gene expression. Such analyses begin to provide insights useful for future genetic engineering of cellulose deposition, in that identification of close orthologs across species may prove useful for prediction of patterns of gene expression and may also aid in prediction of mutant combinations that may be necessary to generate severe phenotypes.
Arabidopsis↗
Chlorophyll breakdown by chlorophyllase: isolation and functional expression of the Chlase1 gene from ethylene-treated Citrus fruit and its regulation during development.
We report on the isolation, functional expression and characterization of a cDNA encoding chlorophyllase, the enzyme catalyzing the first step in the chlorophyll breakdown pathway. The Chlase1 cDNA from Valencia Orange (Citrus sinensis cv. Valencia) was obtained by RT-PCR using degenerate primers based on the amino acid sequence of the previously purified protein. Chlase1 encodes a protein of 329 amino acids, including a sequence domain characterizing serine-lipases and a putative chloroplast-directing transit peptide. The Chlase1 gene encodes an active chlorophyllase enzyme which catalyzes the dephytylation of chlorophyll as shown by in vitro recombinant enzyme assays. Chlorophyllase expression at the transcript level in Valencia orange peel was found to be low and constitutive during natural fruit development without significant increase towards color-break and ripening. However, ethylene treatment induced an increase in chlorophyllase transcript at all stages of development. An enhanced response to ethylene treatment was observed during the months of October and November, corresponding to the time of natural color-break. The senescence-delaying regulator gibberellin-A3 (GA3) inhibited the effect of ethylene on chlorophyllase transcript accumulation. The data presented suggest that chlorophyllase may not be the regulator of chlorophyll breakdown during natural fruit ripening but is consistent with the notion that chlorophyll is gradually degraded during ripening due to a negative balance between synthesis and breakdown. According to this model, exogenous application of ethylene accelerates chlorophyll breakdown due to increased de novo synthesis of chlorophyllase. Further experimentation on the regulation and role of chlorophyllase in planta will be facilitated by the gene tools established in this work.
Amino Acid Sequence↗
Biofeedback-assisted relaxation training with brain injured patients in acute stages of recovery.
There are few published accounts or empirical studies of biofeedback-assisted relaxation training with brain injured patients still in acute stages of recovery. Given the efficacy of biofeedback-assisted relaxation training with other medical populations, brain injured patients in acute stages of recovery with anxiety-based symptoms may also stand to gain some benefits from this form of treatment. It has yet to be determined, however, if severe cognitive impairment or disorientation contraindicate biofeedback treatment. The cases profiled here tentatively suggest that consideration of biofeedback-assisted relaxation training, even for severely cognitively impaired brain injured patients in acute stages of recovery, may be appropriate. Empirical investigations will be needed to determine selection criteria and contraindications for biofeedback treatment in the acute brain injury population.
Acute Disease↗
Some virtual reality and telemedicine applications useful for long duration spaceflight from a systems engineering perspective.
This paper presents a review of virtual reality, telemedicine, and systems engineering design concepts that relate to the human performance of mission tasks during long duration spaceflight. A Mini-Case Study of the MIR/Progress collision is discussed and serves to highlight some of the key issues. We review some physiologic changes which occur as a result of long duration spaceflight, discuss issues associated with performing required mission tasks, and integrate concepts from telemedicine and virtual reality as possible methods and technologies to alleviate some of the deleterious effects of extended space missions.
Disasters↗
Educating families and caretakers of traumatically brain injured patients in the new health care environment: a three phase model and bibliography.
Shorter inpatient stays for traumatically brain injured patients frequently allow less time for comprehensive education of families and caretakers. What is needed to compensate for the shortened duration of brain injury rehabilitation in many settings is a family educational programme that (1) satisfies the family's acute information needs as they arise, and (2) standardizes the delivery of information so that certain knowledge criteria are met. The following article proposes a three phase model of family and caretaker education with an accompanying bibliographical index.
Brain Injuries↗
Obsessional disorders during recovery from severe head injury: report of four cases.
Four cases of transient obsessional disorders following severe head injury are described within the context of recovery from acute traumatic brain injury (TBI). Obsessional features following TBI have important treatment implications in brain injury rehabilitation settings, since emergence of this disorder in the acutely brain injured patient poses a significant obstacle to interdisciplinary rehabilitation. Although the numbers of patients described here and in previous reports are too small to draw conclusions about the incidence of obsessional disorders following TBI, these cases illustrate the importance of correctly identifying and treating obsessional symptoms in the brain injured patient.
Adult↗
Geometrical properties and torsional fatigue life of a tibial interlocking intramedullary nail segment.
OBJECTIVES: The first goal was to present details of a methodology for selecting the cross-sectional geometry and associated dimensions for a tibial interlocking intramedullary (i.m.) nail segment, given a set of candidate geometries. The second goal was to study the effect of four variables on the torsional fatigue life of specimens that constitute a segment of a tibial i.m. nail. METHODS: For the cross-sectional geometry study, the geometric element modeling and analysis method was used to obtain the areas (A) and moments of inertia (I and J) of each of the cross-sectional geometries in the set considered. In the fatigue tests, a specimen was subjected to a load at the end of a lever arm, through an actuator, at a fixed frequency. RESULTS: On the basis of the values of the A, I, and J and consideration of compatibility with the biological envelope, the hourglass cross-section geometry was selected as the best compromise. The cannulation, fillet radius, and main radius of this hourglass were determined to be 3.96, 1.02, and 4.06 millimeters, respectively. Fatigue test specimens fabricated from Ti-6Al-4V and having three sets of additional characteristics performed equally well as those fabricated from 316L stainless steel. These sets of characteristics are hourglass cross-section and mill annealed only; hourglass cross-section and mill annealed, followed by machining and anodization to give a gray coating; and cloverleaf cross-section and mill annealed, followed by machining and anodization to give a gray coating. CONCLUSION: Tibial IM nails with hourglass cross-sectional shape and fabricated of Ti-6Al-4V or Ti-13Nb-13Zr alloy, having appropriate mechanical, thermal, and surface treatments, may be competitive with the current "gold standard" (namely cloverleaf cross-section and fabricated of 316L stainless steel in the cold-worked state).
Bone Nails↗
Herpes simplex type 2 infection in a cohort aged 21 years.
OBJECTIVES: To measure the prevalence of HSV-2 antibodies in a birth cohort of 21 year old New Zealanders from whom detailed sexual histories had been obtained, and to assess the potential for HSV-2 serology in characterising a young adult population's risk for sexually transmitted diseases (STD). METHODS: Sera from 784 cohort members were tested using an indirect IgG enzyme linked immunoassay specific to the HSV-2 glycoprotein G. Positive results were confirmed by western blot. RESULTS: In all, 27 subjects were seropositive for HSV-2 (3.4%), only seven of whom gave a history of genital herpes (26%). Risk among females increased with lifetime number of partners, while risk for males increased with having a first partner who was aged 16 years or under. CONCLUSIONS: The seroprevalence of HSV-2 infection in this cohort was low, but similar to that seen in several other populations in this age group. HSV-2 seropositivity did not appear to be a sensitive marker for high risk sexual activity in this young population. This may be because a critical mass of HSV-2 carriers has not accumulated among potential partners by age 21 years.
Adult↗
Induction of a Citrus gene highly homologous to plant and yeast thi genes involved in thiamine biosynthesis during natural and ethylene-induced fruit maturation.
Maturing citrus fruit undergo pigment changes which can be enhanced by exogenous ethylene. In order to identify genes induced by ethylene in citrus fruit peel, we cloned the gene c-thi1. mRNA corresponding to c-thi1 increased gradually in the peel during natural fruit maturation and in response to ethylene. GA3 pretreatment reduced the inductive effect of ethylene. Levels of c-thi1 increased also in juice sacs but the effect of ethylene was much less prominent. c-thi1 is homologous to yeast and plant genes encoding for an enzyme belonging to the pathway of thiamine biosynthesis. The data suggest that thiamine is involved in citrus fruit maturation.
Adenine↗