Evolution of phenotypic disparity in the plant kingdom.

The plant kingdom exhibits diverse bodyplans, from single-celled algae to complex multicellular land plants, but it is unclear how this phenotypic disparity was achieved. Here we show that the living divisions comprise discrete clusters within morphospace, separated largely by reproductive innovations, the extinction of evolutionary intermediates and lineage-specific evolution. Phenotypic complexity correlates not with disparity but with ploidy history, reflecting the role of genome duplication in plant macroevolution. Overall, the plant kingdom exhibits a pattern of episodically increasing disparity throughout its evolutionary history that mirrors the evolutionary floras and reflects ecological expansion facilitated by reproductive innovations. This pattern also parallels that seen in the animal and fungal kingdoms, suggesting a general pattern for the evolution of multicellular bodyplans.

Piecing together the eophytes - a new group of ancient plants containing cryptospores.

The earliest evidence for land plants comes from dispersed cryptospores from the Ordovician, which dominated assemblages for 60 million years. Direct evidence of their parent plants comes from minute fossils in Welsh Borderland Upper Silurian to Lower Devonian rocks. We recognize a group that had forking, striated axes with rare stomata terminating in valvate sporangia containing permanent cryptospores, but their anatomy was unknown especially regarding conducting tissues. Charcoalified fossils extracted from the rock using HF were selected from macerates and observed using scanning electron microscopy. Promising examples were split for further examination and compared with electron micrographs of the anatomy of extant bryophytes. Fertile fossil axes possess central elongate cells with thick walls bearing globules, occasional strands and plasmodesmata-sized pores. The anatomy of these cells best matches desiccation-tolerant food-conducting cells (leptoids) of bryophytes. Together with thick-walled epidermal cells and extremely small size, these features suggest that these plants were poikilohydric. Our new data on conducting cells confirms a combination of characters that distinguish the permanent cryptospore-producers from bryophytes and tracheophytes. We therefore propose the erection of a new group, here named the Eophytidae (eophytes).

Earliest record of transfer cells in Lower Devonian plants.

Key sources of information on the nature of early terrestrial ecosystems are the fossilized remains of plants and associated organic encrustations, which are interpreted as either biofilms, biological soil crusts or lichens. The hypothesis that some of these encrustations might be the remains of the thalloid gametophytes of embryophytes provided the stimulus for this investigation. Fossils preserved in charcoal were extracted from Devonian Period (Lochkovian Stage, c. 410-419 Myr old) sediments at a geological site in Shropshire (UK). Scanning electron micrographs (SEMs) of the fossils were compared with new and published SEMs of extant bryophytes and tracheophytes, respectively. One specimen was further prepared and imaged by transmission electron microscopy. Fossils of thalloid morphology were composed almost entirely of cells with labyrinthine ingrowths; these also were present in fossils of axial morphology where they were associated with putative food-conducting cells. Comparison with modern embryophytes demonstrates that these distinctive cells are transfer cells (TCs). Our fossils provide by far the earliest geological evidence of TCs. They also show that some organic encrustations are the remains of thalloid land plants and that these are possibly part of the life cycle of a newly recognized group of plants called the eophytes.

The effect of time on packed cell volume following packed red blood cell transfusion in anemic dogs.

OBJECTIVE: To compare the PCV at several timepoints following packed red blood cell (pRBC) administration to anemic dogs and to assess if underlying cause of anemia or regenerative status significantly affects these measurements. DESIGN: Prospective, observational study from November 2016 to October 2017. SETTING: A small animal emergency and specialty hospital. ANIMALS: Forty-six anemic client-owned dogs that received a total of 50 pRBC transfusions for management of anemia. INTERVENTIONS: Blood was collected, and a PCV was obtained prior to pRBC transfusion (T0), immediately after (T1), 30 minutes after (T2), 1 hour after (T3), 2 hours after (T4), and 4 hours after (T5) the transfusion. Underlying causes of anemia were classified as hemorrhage, hemolysis, and ineffective erythropoiesis. Dogs were also categorized in regard to regenerative status of anemia and the presence or absence of expected continued blood loss or destruction. MEASUREMENTS AND MAIN RESULTS: The mean PCV at T0 was 0.15 L/L (15%). After administration of a pRBC transfusion, the mean PCV at T1 was 0.28 L/L (28%). For all other timepoints (T2, T3, T4, and T5), the mean PCV was 0.27 L/L (27%). The PCV did not change significantly over time post-transfusion (P = 0.184), and no pairwise combinations of times differed significantly (paired t-tests; P > 0.05 for all). When dogs were categorized via regeneration status and continued blood loss or hemolysis, results were consistent. CONCLUSIONS: There was no significant change in PCV from the value obtained immediately after pRBC transfusion up to 4 hours post-transfusion in dogs with several different causes of anemia. These results suggest that obtaining a PCV immediately after administering a pRBC transfusion to an anemic dog may be just as reliable as obtaining a measurement 2 hours after the transfusion. This remains true for dogs with expected continued red blood cell loss or destruction.

Mid-Devonian Archaeopteris Roots Signal Revolutionary Change in Earliest Fossil Forests.

The origin of trees and forests in the Mid Devonian (393-383 Ma) was a turning point in Earth history, marking permanent changes to terrestrial ecology, geochemical cycles, atmospheric CO2 levels, and climate. However, how all these factors interrelate remains largely unknown. From a fossil soil (palaeosol) in the Catskill region near Cairo NY, USA, we report evidence of the oldest forest (mid Givetian) yet identified worldwide. Similar to the famous site at Gilboa, NY, we find treefern-like Eospermatopteris (Cladoxylopsida). However, the environment at Cairo appears to have been periodically drier. Along with a single enigmatic root system potentially belonging to a very early rhizomorphic lycopsid, we see spectacularly extensive root systems here assigned to the lignophyte group containing the genus Archaeopteris. This group appears pivotal to the subsequent evolutionary history of forests due to possession of multiple advanced features and likely relationship to subsequently dominant seed plants. Here we show that Archaeopteris had a highly advanced root system essentially comparable to modern seed plants. This suggests a unique ecological role for the group involving greatly expanded energy and resource utilization, with consequent influence on global processes much greater than expected from tree size or rooting depth alone.

The Interrelationships of Land Plants and the Nature of the Ancestral Embryophyte.

The evolutionary emergence of land plant body plans transformed the planet. However, our understanding of this formative episode is mired in the uncertainty associated with the phylogenetic relationships among bryophytes (hornworts, liverworts, and mosses) and tracheophytes (vascular plants). Here we attempt to clarify this problem by analyzing a large transcriptomic dataset with models that allow for compositional heterogeneity between sites. Zygnematophyceae is resolved as sister to land plants, but we obtain several distinct relationships between bryophytes and tracheophytes. Concatenated sequence analyses that can explicitly accommodate site-specific compositional heterogeneity give more support for a mosses-liverworts clade, "Setaphyta," as the sister to all other land plants, and weak support for hornworts as the sister to all other land plants. Bryophyte monophyly is supported by gene concatenation analyses using models explicitly accommodating lineage-specific compositional heterogeneity and analyses of gene trees. Both maximum-likelihood analyses that compare the fit of each gene tree to proposed species trees and Bayesian supertree estimation based on gene trees support bryophyte monophyly. Of the 15 distinct rooted relationships for embryophytes, we reject all but three hypotheses, which differ only in the position of hornworts. Our results imply that the ancestral embryophyte was more complex than has been envisaged based on topologies recognizing liverworts as the sister lineage to all other embryophytes. This requires many phenotypic character losses and transformations in the liverwort lineage, diminishes inconsistency between phylogeny and the fossil record, and prompts re-evaluation of the phylogenetic affinity of early land plant fossils, the majority of which are considered stem tracheophytes.

The timescale of early land plant evolution.

Establishing the timescale of early land plant evolution is essential for testing hypotheses on the coevolution of land plants and Earth's System. The sparseness of early land plant megafossils and stratigraphic controls on their distribution make the fossil record an unreliable guide, leaving only the molecular clock. However, the application of molecular clock methodology is challenged by the current impasse in attempts to resolve the evolutionary relationships among the living bryophytes and tracheophytes. Here, we establish a timescale for early land plant evolution that integrates over topological uncertainty by exploring the impact of competing hypotheses on bryophyte-tracheophyte relationships, among other variables, on divergence time estimation. We codify 37 fossil calibrations for Viridiplantae following best practice. We apply these calibrations in a Bayesian relaxed molecular clock analysis of a phylogenomic dataset encompassing the diversity of Embryophyta and their relatives within Viridiplantae. Topology and dataset sizes have little impact on age estimates, with greater differences among alternative clock models and calibration strategies. For all analyses, a Cambrian origin of Embryophyta is recovered with highest probability. The estimated ages for crown tracheophytes range from Late Ordovician to late Silurian. This timescale implies an early establishment of terrestrial ecosystems by land plants that is in close accord with recent estimates for the origin of terrestrial animal lineages. Biogeochemical models that are constrained by the fossil record of early land plants, or attempt to explain their impact, must consider the implications of a much earlier, middle Cambrian-Early Ordovician, origin.

The origin and early evolution of vascular plant shoots and leaves.

The morphology of plant fossils from the Rhynie chert has generated longstanding questions about vascular plant shoot and leaf evolution, for instance, which morphologies were ancestral within land plants, when did vascular plants first arise and did leaves have multiple evolutionary origins? Recent advances combining insights from molecular phylogeny, palaeobotany and evo-devo research address these questions and suggest the sequence of morphological innovation during vascular plant shoot and leaf evolution. The evidence pinpoints testable developmental and genetic hypotheses relating to the origin of branching and indeterminate shoot architectures prior to the evolution of leaves, and demonstrates underestimation of polyphyly in the evolution of leaves from branching forms in 'telome theory' hypotheses of leaf evolution. This review discusses fossil, developmental and genetic evidence relating to the evolution of vascular plant shoots and leaves in a phylogenetic framework.This article is part of a discussion meeting issue 'The Rhynie cherts: our earliest terrestrial ecosystem revisited'.

Characterization of dexmedetomidine dosing and safety in neonates and infants.

OBJECTIVES: To describe and compare off-label use and cardiovascular (CV) adverse effects of dexmedetomidine in neonates and infants in the pediatric intensive care unit (PICU). METHODS: Patients younger than 12 months with corrected gestational ages of at least 37 weeks who were receiving continuous infusion of dexmedetomidine at a tertiary pediatric referral center between October 2007 and August 2012 were assessed retrospectively. Patients were excluded if dexmedetomidine was used for procedural sedation, postoperative CV surgery, or if postanesthesia infusion weaning orders existed at the time of PICU admission. RESULTS: The median minimum dexmedetomidine dose was similar between infants and neonates at 0.2 mcg/kg/hr (IQR, 0.17-0.3) versus 0.29 mcg/kg/hr (IQR, 0.2-0.31), p = 0.35. The median maximum dose was higher for infants than neonates (0.6 mcg/kg/hr [IQR, 0.4-0.8] vs. 0.4 mcg/kg/hr [IQR, 0.26-0.6], p < 0.01). Additional sedative use was more common in infants than neonates (75/99 [76%] vs. 15/28 [54%], p = 0.02). At least 1 episode of hypotension was noted in 34/127 (27%) patients and was similar between groups. An episode of bradycardia was identified more frequently in infants than neonates (55/99 [56%] vs. 2/28 [7%], p < 0.01). Significant reduction in heart rate and systolic blood pressure was noted when comparing baseline vital signs to lowest heart rate and systolic blood pressure during infusion (p < 0.01). CONCLUSIONS: Dexmedetomidine dose ranges were similar to US Food and Drug Administration-labeled dosages for intensive care unit sedation in adults. More infants than neonates experienced a bradycardia episode, but infants were also more likely to receive higher dosages of dexmedetomidine and additional sedatives.

Implementation of a diuretic stewardship program in a pediatric cardiovascular intensive care unit to reduce medication expenditures.

PURPOSE: The implementation of a diuretic stewardship program in a pediatric cardiovascular intensive care unit (ICU) is described. METHODS: This retrospective study compared the use of i.v. chlorothiazide and i.v. ethacrynic acid in pediatric cardiovascular surgery patients before and after implementation of a diuretic stewardship program. All pediatric patients admitted to the pediatric cardiovascular service were included. The cardiovascular surgery service was educated on formal indications for specific diuretic agents, and the diuretic stewardship program was implemented on January 1, 2013. Under the stewardship program, i.v. ethacrynic acid was indicated in patients with a sulfonamide allergy, and i.v. chlorothiazide was considered appropriate in patients receiving maximized i.v. loop diuretic doses. A detailed review of the pharmacy database and medical records was performed for each patient to determine i.v. chlorothiazide and i.v. ethacrynic acid use and expenditures, appropriateness of use, days using a ventilator, and cardiovascular ICU length of stay. RESULTS: After implementation of diuretic stewardship, the use of i.v. chlorothiazide decreased by 74% (531 fewer doses) while i.v. ethacrynic acid use decreased by 92% (47 fewer doses), resulting in a total reduction of $91,398 in expenditures on these diuretics over the six-month study period and an estimated annual saving of over $182,000. The median number of days using a ventilator and the length of ICU stay did not differ significantly during the study period. CONCLUSION: Implementation of a diuretic stewardship program reduced the use of i.v. chlorothiazide and i.v. ethacrynic acid without adversely affecting clinical outcomes such as ventilator days and length of stay in a pediatric cardiovascular ICU.

Antimicrobial prophylaxis for external ventricular drains in pediatric neurosurgical patients.

BACKGROUND: Our goal was to describe the use of antibiotics for surgical prophylaxis of external ventricular drains (EVDs) in a pediatric neurosurgical population and determine the incidence of EVD-related infections among different antimicrobial prophylaxis strategies. MAIN OUTCOME MEASURES: This retrospective chart review included patients up to 18 years old who underwent EVD insertion at either of two tertiary care academic hospitals in the same health system between August 1, 2008, and July 31, 2012. Patients were included if they received at least one dose of antibiotics before EVD insertion. Patients who received only perioperative antibiotics were compared with those who also received antibiotics after this period. The primary endpoint was incidence of EVD-related infection. Descriptive statistics were used to summarize baseline characteristics and compare antibiotic regimens between groups. Pearson's chi square and Mann Whitney U tests compared nonparametric data. RESULTS: A total of 182 EVD insertions were documented, and 88 included in the study. Of these 88, 27 were associated only with perioperative doses of antibiotics, and 61 with prolonged antibiotic use. Baseline characteristics and antibiotic choices were similar between the groups. At least 55 (63%) catheters were antibiotic-impregnated, but types of catheters couldn't be compared between groups due to insufficient data. No central nervous system infections were identified in either group, so the primary objective could not be evaluated statistically. CONCLUSION: No infections were identified in any study subjects during EVD treatment. An adequately powered, multi-center prospective study should be performed to determine if prolonged use of antibiotics beyond the perioperative period is of benefit.

Impact of a Drug Shortage on Medication Errors and Clinical Outcomes in the Pediatric Intensive Care Unit.

OBJECTIVES: The purpose of this study was to assess the rate of prescribing errors, resulting adverse events, and patient outcomes associated with sedation and analgesia in the pediatric intensive care unit (PICU) before and during a national shortage of fentanyl and injectable benzodiazepines. METHODS: A retrospective chart review was performed of patients admitted to the PICU with at least 1 prescribed order for a sedative or analgesic agent during the time periods of January to February of 2011 and 2012. Initial orders for sedative and analgesic agents were identified and investigated for appropriateness of dose and were assessed for error-associated adverse events. Orders were stratified by timing in regard to clinical pharmacist on-site availability. Demographic and outcome information, including unintended extubations, ventilator days, and PICU length of stay, were gathered. RESULTS: One hundred sixty-nine orders representing 72 patients and 179 orders representing 75 patients in 2011 and 2012, respectively, were included in analysis. No differences were found in the rate of prescribing errors in 2011 and 2012 (33 errors in 169 orders vs. 39 errors in 179 orders, respectively, p=0.603). No differences were found in rates of prescribing errors in regard to clinical pharmacist on-site availability. A significant increase was seen in unintended extubations per 100 ventilator days, with 0.15 in 2011 vs. 1.13 in 2012, respectively (p<0.001). A significant decrease was seen in ventilator days per patient (p<0.001) and PICU length of stay per patient (p=0.019). CONCLUSIONS: There were no differences in rates of prescribing errors before versus during the fentanyl and benzodiazepine shortage.

Cryptospores and cryptophytes reveal hidden diversity in early land floras.

Cryptospores, recovered from Ordovician through Devonian rocks, differ from trilete spores in possessing distinctive configurations (i.e. hilate monads, dyads, and permanent tetrads). Their affinities are contentious, but knowledge of their relationships is essential to understanding the nature of the earliest land flora. This review brings together evidence about the source plants, mostly obtained from spores extracted from minute, fragmented, yet exceptionally anatomically preserved fossils. We coin the term 'cryptophytes' for plants that produced the cryptospores and show them to have been simple terrestrial organisms of short stature (i.e. millimetres high). Two lineages are currently recognized. Partitatheca shows a combination of characters (e.g. spo-rophyte bifurcation, stomata, and dyads) unknown in plants today. Lenticulatheca encompasses discoidal sporangia containing monads formed from dyads with ultrastructure closer to that of higher plants, as exemplified by Cooksonia. Other emerging groupings are less well characterized, and their precise affinities to living clades remain unclear. Some may be stem group embryophytes or tracheophytes. Others are more closely related to the bryophytes, but they are not bryophytes as defined by extant representatives. Cryptophytes encompass a pool of diversity from which modern bryophytes and vascular plants emerged, but were competitively replaced by early tracheophytes. Sporogenesis always produced either dyads or tetrads, indicating strict genetic control. The long-held consensus that tetrads were the archetypal condition in land plants is challenged.

Velaglucerase alfa for the management of type 1 Gaucher disease.

BACKGROUND: Gaucher disease (GD) is the most common lysosomal storage disease, (frequency of 1:40,000 to 1:60,000). Ninety-Five percent of patients have type 1 (nonneuropathic type). Symptomatic patients with type 1 GD are treated with enzyme replacement therapy (ERT) to improve disease-induced effects on hemoglobin, platelets, and liver and spleen volume. Currently, several ERTs are available. OBJECTIVE: The goal of this article was to review the pharmacology, efficacy, and safety data available for the use of a recently approved ERT, velaglucerase alfa, for the treatment of type 1 GD in symptomatic pediatric and adult patients. METHODS: Serial searches of MEDLINE, EMBASE, and Cochrane databases for English-language, peer-reviewed, clinical data (using the search term velaglucerase alfa) were completed, with the final search in November 2011. All identified, peer-reviewed published human data were used for this review. Due to minimal peer-reviewed published data, those data reported via clinical trial registries or in the form of published abstracts were included. The manufacturer was contacted and given the opportunity to submit supplemental data for consideration of inclusion by the author. RESULTS: Velaglucerase alfa is produced through gene activation technology and is identical to wild-type enzyme. As with other ERTs for type 1 GD, velaglucerase alfa targets accumulated glucocerebroside primarily within the lysosome of the macrophages in the affected organs and systems. When administered at doses of 60 U/kg intravenously, velaglucerase alfa follows linear pharmacokinetics and is rapidly eliminated, with a mean (SD) residence time or time for 63% of the dose to be cleared from systemic circulation of 14 (4) minutes. Four trials and early access program data reporting efficacy were identified for this review: 5 peer-reviewed publications, 3 clinical trial registry reports, and 1 abstract-only publication. Phase I/II data with an extension phase (n = 12) showed significant improvements (all, P < 0.004) in hemoglobin concentrations (21.7%), platelet counts (157.8%), and hepatic (-42.8%) and spleen (-79.3%) volumes at 48 months. Bone mineral density data reported out to 69 months for this extension population noted significant improvements in z score slope for both lumbar spine (0.14 z score unit per year; P < 0.01) and femoral head (0.08 z score unit per year; P < 0.01). Benchmarking of 7 patients with complete clinical datasets at 57 months identified achievement and maintenance of therapeutic goals set by the International Collaborative Gaucher Group for anemia, platelet counts, hepatosplenomegaly, and bone mineral density. Thirty-eight patients enrolled in an open-label, therapy-switch trial who received velaglucerase alfa at doses consistent with current doses of imiglucerase maintained hemoglobin (-0.101 g/dL [95% CI, -0.272 to 0.07]) and platelet counts (7.04% [95% CI, 0.54% to 13.53%]) at 53 weeks after therapy change. Phase III data evaluating 2 dosing regimens of velaglucerase alfa 60 and 45 U/kg intravenously every other week reported significant improvements in most measured clinical parameters at 12 months: hemoglobin concentrations (60 U/kg, 2.429 [0.324] g/dL [P < 0.0001]; 45 U/kg, 2.438 g/dL [95% CI, 1.488 to 3.389]), platelet counts (60 U/kg, 50.88 × 10(9)/L [95% CI, 23.97 to 77.78]; 45 U/kg, 40.92 × 10(9)/L [95% CI, 11.2 to 70.64]), spleen volumes (60 U/kg, -1.92% of body weight [95% CI, -3.04 to -0.79]; 45 U/kg, -1.87% of body weight [95% CI, -3.17 to -0.57]), and hepatic volumes (60 U/kg, -0.84% of body weight [95% CI, -1.58 to -0.11]). A subanalysis of the pediatric population showed clinical improvements at 12 months in both dosing groups: hemoglobin concentrations (60 U/kg, 1.74 g/dL [95% CI, 0.72 to 2.78]; 45 U/kg, 2.77 g/dL [95% CI, -0.99 to 6.53]), platelet counts (60 U/kg, 49.9 × 10(9)/L [95% CI, -32.1 to 131.9]; 45 U/kg, 60.3 × 10(9)/L [95% CI, -103.1 to 223.7]), spleen volumes (60 U/kg, -2.1 cm(3) [95% CI, -5.3 to 1.1]; 45 U/kg, -0.7 cm(3) [95% CI, -2.6 to 1.2]), and hepatic volumes (60 U/kg, -0.7 cm(3) [95% CI, -1.4 to 0.0]; 45 U/kg, -0.3 cm(3) [95% CI, -1.7 to 1.1]). Data comparing velaglucerase alfa with imiglucerase identified similar changes in hemoglobin concentrations at 1.624 g/dL and 1.488 g/dL, respectively, after 9 months of therapy. Safety was reported in 3 identified studies and in data reported from the early access program: 3 peer-reviewed publications, 3 studies reported in clinical trial registries, and 1 abstract publication. Patients experienced a minimal number of adverse effects, and most reactions were mild to moderate in severity; 1 patient developed an anaphylactoid reaction and was discontinued from the trial. Antibody formation has been described with velaglucerase alfa but when compared with that of imiglucerase, seroconversion is less frequent (1% and 23%, respectively). Dosing regimens, from 30 to 60 U/kg intravenously every other week, have been assessed. Currently, the manufacturer recommends 60 U/kg intravenously every other week; however, further studies and evaluation of current study dosing regimens are needed to determine if there is a lower effective dose. CONCLUSIONS: Although a minimal amount of data are available for this relatively new biological agent, velaglucerase alfa reportedly is effective in the achievement and maintenance of therapeutic goals in type 1 GD in both treatment-naive and patients previously treated with imiglucerase. This agent has been reasonably well tolerated in clinical trials and may be considered for use in symptomatic patients with type 1 GD.

Assessment of web-based training modules on learning facilitation for advanced pharmacy practice experiences in pediatrics.

OBJECTIVES: To assess the effectiveness of web-based training (WBT) modules to enhance and facilitate student pharmacists' learning and their ability to provide pharmaceutical care to children during a pediatric advanced pharmacy practice experience (APPE). METHODS: Pediatric-specific WBT modules were developed for completion by APPE students during a 4-week rotation. Pediatric modules covered developmental pharmacology; antimicrobial use and monitoring; fluids, electrolytes, and dehydration; and drug information. Students were responsible for completing all modules within the first week of the APPE. Preassessments and postassessments consisted of 8 to 10 multiple-choice questions, with scores ranging from 0 to 100 points. Data were analyzed using descriptive statistics and paired t tests. RESULTS: Statistically significant improvements in postassessment scores were achieved for 3 of the 4 modules. Significant improvements were not observed in the antimicrobial use and monitoring module. Most student pharmacists either somewhat or strongly agreed that the modules improved their understanding of pharmaceutical care for children. CONCLUSIONS: WBT modules, taken during an APPE rotation, may expand and improve student pharmacists' understanding of pharmaceutical care in pediatric patients.

Continuous infusion of nafcillin for sternal osteomyelitis in an infant after cardiac surgery.

We report the use of the continuous infusion of nafcillin for the treatment of an infant who had methicillinsusceptible Staphylococcus aureus sternal osteomyelitis not responsive to traditional nafcillin dosing. The patient was successfully treated with surgical debridement and the continuous infusion of nafcillin. To our knowledge, this is the first report describing the successful use of the continuous infusion of nafcillin to treat an infant who had sternal osteomyelitis after cardiac surgery.

Sildenafil for the treatment of pulmonary hypertension in pediatric patients.

Sildenafil is a phosphodiesterase 5 inhibitor widely used for the treatment of pulmonary hypertension in children. Despite limited available safety and efficacy evidence, use of sildenafil continues to increase. To date, sildenafil use for pediatric pulmonary hypertension has been characterized for 193 children through 16 studies and 28 case series and reports. The primary efficacy data suggest that sildenafil is beneficial for facilitating the weaning of inhaled nitric oxide in children after cardiac surgery. Compiled safety data suggest that sildenafil is well tolerated among children with idiopathic pulmonary arterial hypertension and pulmonary arterial hypertension associated with congenital heart disease. This review summarizes the available data describing the use, safety, and efficacy of sildenafil for children with pulmonary hypertension.

Effect of two types of soy milk and dairy milk on plasma lipids in hypercholesterolemic adults: a randomized trial.

OBJECTIVE: To compare the effects of two commercially available soy milks (one made using whole soy beans, the other using soy protein isolate) with low-fat dairy milk on plasma lipid, insulin, and glucose responses. DESIGN: Randomized clinical trial, cross-over design. SUBJECTS: Participants were 30-65 years of age, n = 28, with pre-study LDL-cholesterol (LDL-C) concentrations of 160-220 mg/dL, not on lipid lowering medications, and with an overall Framingham risk score of or=4 weeks. RESULTS: Mean LDL-C concentration at the end of each phase (+/- SD) was 161 +/- 20, 161 +/- 26 and 170 +/- 24 mg/dL for the whole bean soy milk, the soy protein isolate milk, and the dairy milk, respectively (p = 0.9 between soy milks, p = 0.02 for each soy milk vs. dairy milk). No significant differences by type of milk were observed for HDL-cholesterol, triacylglycerols, insulin, or glucose. CONCLUSION: A 25 g dose of daily soy protein from soy milk led to a modest 5% lowering of LDL-C relative to dairy milk among adults with elevated LDL-C. The effect did not differ by type of soy milk and neither soy milk significantly affected other lipid variables, insulin or glucose.

New Antiretroviral Therapies for Pediatric HIV Infection.

Human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome affect millions of children worldwide. The development of antiretroviral therapy has significantly improved the morbidity and mortality of pediatric patients infected with HIV. Currently, 4 classes of antiretroviral agents exist: nucleoside / nucleotide reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, protease inhibitors, and entry inhibitors. A total of 21 single-entity antiretroviral agents and 4 co-formulated antiretroviral products hold Food and Drug Administration (FDA) approval for treatment of HIV-1 infection. However, not all of these agents are indicated for use in patients less than 18 years of age. Since the year 2000, 7 new antiretroviral agents (atazanavir, emtricitabine, enfuvirtide, fosamprenavir, lopinavir/ritonavir, tenofovir, and tipranavir) have been approved by the FDA for use in adult patients as part of combination therapy for the treatment of HIV-1 infection. Although only 3 of these newer agents (emtricitabine, enfuvirtide, and lopinavir/ritonavir) are currently FDA approved for use in pediatric patients, pediatric clinical studies of the other 4 new agents are currently underway. The purpose of this article is to review these 7 new antiretroviral agents and describe their roles in the treatment of pediatric HIV infection. For each drug, the following information will be addressed: FDA-approved indication and age groups, clinical efficacy, pharmacokinetics, adverse drug reactions, clinically relevant drug interactions, pediatric and adult dosing, dosage forms, administration, and place in the treatment of pediatric HIV infection.