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Review of intravenous immunoglobulin replacement therapy trials for primary humoral immunodeficiency patients

An available supply of intravenous immunoglobulin (IVIG) is essential for individuals with primary humoral immunodeficiency. A shortage in 1997 prompted the Food and Drug Administration (FDA) to revise guidelines for the licensure, production, and distribution of new IVIG products, including the standardization of United States clinical trials regarding endpoints for safety, efficacy, and pharmacokinetics. The following review is intended to present current information and results of clinical trials in patients with primary immunodeficiency treated with IVIG products currently licensed or awaiting licensure in the United States. The data presented are compiled from published clinical trials and prescribing information generated by manufacturers.     

A Group Randomized Intervention Trial Increases Participation in the School Breakfast Program in 16 Rural High Schools in Minnesota

BackgroundBreakfast consumption is associated with better diet quality and healthier weights, yet many adolescents miss breakfast. Nationally, 17.1% of students participate in the School Breakfast Program (SBP). Only 10% of high school students participate.ObjectiveOur aim was to evaluate an environmental intervention to increase SBP participation in high schools.DesignA group randomized trial was carried out from 2012 to 2015.Participants/settingNinth- and 10th-grade students enrolled in 16 rural schools in Minnesota (median 387 students) were randomized to intervention or control condition.InterventionA school-based intervention that included two key components was implemented over a 12-month period. One component focused on increasing SBP participation by increasing student access to school breakfast through changes in school breakfast service practices (eg, serving breakfast from a grab-n-go cart in the atrium; expanding breakfast service times). The other component focused on promoting school breakfast through student-directed marketing campaigns.Main outcome measureChange in school-level participation in the SBP was assessed between baseline (among ninth and tenth graders) and follow-up (among tenth and eleventh graders). School meal and attendance records were used to assess change in school-level participation rates in the SBP.Statistical analysesThe Wilcoxon test was used for analysis of difference in change in mean SBP participation rate by experimental group.ResultsThe median change in SBP participation rate between baseline and follow-up was 3% (interquartile range=13.5%) among the eight schools in the intervention group and 0.5% (interquartile range=0.7%) among the eight schools in the control group. This difference in change between groups was statistically significant (Wilcoxon test, P=0.03). The intervention effect increased throughout the intervention period, with change in mean SBP participation rate by the end of the school year reaching 10.3% (95% CI 3.0 to 17.6). However, among the intervention schools, the change in mean SBP participation rates was highly variable (range=–0.8% to 24.8%).ConclusionsInterventions designed to improve access to the SBP by reducing environmental and social barriers have potential to increase participation among high school students.     

Sex-specific mating pheromones in the nematode Panagrellus redivivus

Nematodes use an extensive chemical language based on glycosides of the dideoxysugar ascarylose for developmental regulation (dauer formation), male sex attraction, aggregation, and dispersal. However, no examples of a female- or hermaphrodite-specific sex attractant have been identified to date. In this study, we investigated the pheromone system of the gonochoristic sour paste nematode Panagrellus redivivus, which produces sex-specific attractants of the opposite sex. Activity-guided fractionation of the P. redivivus exometabolome revealed that males are strongly attracted to ascr#1 (also known as daumone), an ascaroside previously identified from Caenorhabditis elegans hermaphrodites. Female P. redivivus are repelled by high concentrations of ascr#1 but are specifically attracted to a previously unknown ascaroside that we named dhas#18, a dihydroxy derivative of the known ascr#18 and an ascaroside that features extensive functionalization of the lipid-derived side chain. Targeted profiling of the P. redivivus exometabolome revealed several additional ascarosides that did not induce strong chemotaxis. We show that P. redivivus females, but not males, produce the male-attracting ascr#1, whereas males, but not females, produce the female-attracting dhas#18. These results show that ascaroside biosynthesis in P. redivivus is highly sex-specific. Furthermore, the extensive side chain functionalization in dhas#18, which is reminiscent of polyketide-derived natural products, indicates unanticipated biosynthetic capabilities in nematodes.     

Public Health Implications of Changing Rodent Importation Patterns – United States, 1999–2013

The United States imports a large volume of live wild and domestic animal species; these animals pose a demonstrated risk for introduction of zoonotic diseases. Rodents are imported for multiple purposes, including scientific research, zoo exhibits and the pet trade. Current U.S. public health regulatory restrictions specific to rodent importation pertain only to those of African origin. To understand the impacts of these regulations and the potential public health risks of international rodent trade to the United States, we evaluated live rodent import records during 1999–2013 by shipment volume and geographic origin, source (e.g. wild‐caught versus captive‐ or commercially bred), intended purpose and rodent taxonomy. Live rodent imports increased from 2737 animals during 1999 to 173 761 animals during 2013. Increases in both the number and size of shipments contributed to this trend. The proportion of wild‐captured imports declined from 75% during 1999 to <1% during 2013. Nearly all shipments during these years were imported for commercial purposes. Imports from Europe and other countries in North America experienced notable increases in volume. Gerbils and hamsters arriving from Europe and chinchillas, guinea pigs and hamsters arriving from other countries in North America were predominant taxa underlying this trend. After 2003, African‐origin imports became sporadic events under the federal permit process. These patterns suggest development of large‐scale captive rodent breeding markets abroad for commercial sale in the United States. While the shift from wild‐captured imports alleviates many conservation concerns and risks for novel disease emergence, such consolidated sourcing might elevate exposure risks for zoonotic diseases associated with high‐density rodent breeding (e.g. lymphocytic choriomeningitis or salmonellosis). A responsive border health system must periodically re‐evaluate importation regulations in conjunction with key stakeholders to ensure a balance between the economic benefits of rodent trade against the potential public health risks.     

Erfolgreiche präklinische Blutstillung mit Chitosan-Gaze

This article presents the case of a patient with haemorrhagic shock due to self-inflicted stab wounds to the chest and upper abdomen during a suicide attempt. Prehospital packing with chitosan gauze resulted in hemostasis and stabilisation of the patient during transport to the hospital. For uncontrolled bleeding from penetrating trauma the use of hemostyptic agents is an important option. The authors believe that hemostyptic agents should be introduced into clinical praxis of emergency medical services (EMS) and their use should be trained by EMS personnel.     

Inactive ERBB Receptors Cooperate With Reactive Oxygen Species To Suppress Cancer Progression

The ERBB receptors are a family of heterodimerization partners capable of driving transformation and metastasis. While the therapeutic targeting of single receptors has proven efficacious, optimal targeting of this receptor family should target all oncogenic members simultaneously. The juxtamembrane domains of ERBB1, ERBB2, and ERBB3 are highly conserved and control various aspects of ERBB-dependent biology. In an effort to block those functions, we have targeted this domain with decoy peptides synthesized in tandem with a cell-penetrating peptide, termed EJ1. Treatment with EJ1 induces cell death, promotes the formation of inactive ERBB multimers, and results in simultaneous reduction of ERBB1, ERBB2, and ERBB3 activation. Treatment also results in the activation of myosin light chain–dependent cell blebbing while inactivating CaMKII signaling, coincident with the induction of cell death. EJ1 also directly translocates to mitochondria, correlating with a loss of mitochondrial membrane potential and production of reactive oxygen species. Finally, treatment of a mouse model of breast cancer with EJ1 results in the inhibition of tumor growth and metastasis without associated toxicities in normal cells. Overall, these data demonstrate that a portion of the ERBB jxm domain, when used as an intracellular decoy, can inhibit tumor growth and metastasis, representing a novel anticancer therapeutic.     

Remodeling of sinus node function after catheter ablation of right atrial flutter

INTRODUCTION: The purpose of this study was to investigate the effect of ablation of right atrial flutter upon sinus node function in humans. METHODS AND RESULTS: This study enrolled 35 patients. Twenty-four patients (16 men and 8 women; age 68 +/- 11 years) were referred for ablation of persistent atrial flutter (duration 8 +/- 11 months). After ablation, there was abnormal sinus node function defined as a corrected sinus node recovery time (CSNRT) > or = 550 msec. The control group consisted of 11 patients who were undergoing pacemaker implantation for sinus node disease but did not have a history of atrial dysrhythmias or ablation. Within 24 hours of ablation or pacemaker implantation, baseline maximal CSNRT was measured through a permanent pacemaker by AAI pacing at six cycle lengths: 600, 550, 500, 450, 400, and 350 msec. CSNRT then was measured in the same manner at 48 hours, 14 days, and 3 months after ablation/pacemaker implantation. P wave amplitude and duration, and percent atrial sensing also were assessed at the same intervals. For patients undergoing atrial flutter ablation, there was progressive temporal recovery of CSNRT (1,204 +/- 671 msec at baseline vs 834 +/- 380 msec at 3 months; P < 0.001) and a significant increase in the percent atrial sensing and P wave amplitude at 3 months compared with baseline (P < 0.001). In control subjects, there was no change in the CSNRT, percent atrial pacing, or P wave amplitude. CONCLUSION: After ablation of persistent atrial flutter, there is temporal recovery of CSNRT and increase in spontaneous atrial activity. These findings suggest that atrial flutter induces reversible changes in sinus node function.