Recombinant α2(IV)NC1 domain of type IV collagen is an effective regulator of retinal capillary endothelial cell proliferation and inhibits pre-retinal neovascularisation

Background A recombinant form of the α2(IV)NC1 domain of type IV collagen has been shown to have potent anti-angiogenic activity although this peptide has not been studied in the context of proliferative retinopathies. In the current investigation we examined the potential for α2(IV)NC1 to regulate retinal microvascular endothelial cell function using a range of in vitro and in vivo assay systems. Materials and methods α2(IV)NC1 at concentrations between 0.1 and 1 μg/ml was added to retinal microvascular endothelial cells (RMECs) followed by assessment of cell attachment, proliferation and survival. This agent was also tested within a novel in vitro three-dimensional retinal angiogenesis assay and the number of angiogenic sprouts quantified. α2(IV)NC1 was also delivered intra-vitreally to mice with oxygen-induced proliferative retinopathy (OIR) and neovascularisation evaluated in comparison with vehicle-treated controls. Results RMECs treated with α2(IV)NC1 (0.1, 0.5 and 1 μg/ml) showed delayed attachment at 3 h post-seeding, although this deficit had been restored at the 6-h time point. BrdU assay of DNA replication revealed that confluent RMECs treated with α2(IV)NC1 showed no measurable response in comparison with vehicle-treated controls. By contrast, proliferation of sub-confluent RMECs was significantly reduced by α2(IV)NC1 at 0.5 μg/ml (P<0.01). α2(IV)NC1 also induced apoptosis in RMECs and inhibited angiogenesis of pre-existing retinal vascular networks in vitro (P<0.001). Intra-vitreal injection of α2(IV)NC1 in the OIR model significantly inhibited pre-retinal neovascularisation compared with vehicle-treated controls (P<0.001). Conclusion α2(IV)NC1 inhibits angiogenesis in the retinal microvasculature. This recombinant protein has potential for the treatment of neovascularisation in proliferative retinopathies. BioStratum Inc. did not sponsor this research in any way. None of the authors are paid consultants with this company.     

Development of the Massachusetts School Nurse Research Network (MASNRN): A Practice-Based Research Network to improve the quality of school nursing practice.

When school nurses embrace evidence-based practice (EBP), higher-quality care is provided to students, their families, and the larger community. Despite this, school nursing has been slow to embrace EBP. Practice-Based Research Networks (PBRNs), which capitalize on the combined strengths of clinicians and researchers to study clinical questions, are one approach to overcoming barriers towards advancing evidence-based practice (EBP) in school nursing. This article will briefly review EBP and PBRNs. The development of Massachusetts School Nurse Research Network (MASNRN), a PBRN designed to investigate health issues common across schools and to validate school nursing practice, will then be described. Details regarding MASNRN's mission, governance, communications systems, staffing, and network maintenance and funding will be explicated. MASNRN can serve as a model for PBRN development within the broader school nursing community.     

Management of infraumbilical vertical scars in DIEP-flaps by crossover anastomosis.

The deep inferior epigastric perforator (DIEP)-flap continues to be the standard treatment in microsurgical breast reconstruction. Reasons for the popularity of the DIEP-flap include the availability of a large amount of tissue for the reconstruction of large breasts, a reliable vascular anatomy and an aesthetically pleasing donor site scar. However, the DIEP-flap is not considered the optimal choice as the donor tissue in all patients. Previous abdominal surgeries with resulting scars may threaten the success of a free DIEP-flap due to compromised vascularity within the flap. We elaborated a technique to increase the safety of breast reconstruction with the DIEP-flap in the presence of an infraumbilical vertical scar. After raising the DIEP-flap in a traditional manner on one side with harvesting of a considerate length of the inferior epigastric vessels, a segment of the superior epigastric vessels is left attached to the main pedicle. This stump of the superior epigastric vessels is now anastomosed under the microscope to a paraumbilical perforator on the contralateral side of the flap for in-flap microvascular augmentation. The above-mentioned technique was applied in five patients who presented with an infraumbilical vertical scar and were reconstructed with a DIEP-flap because of breast cancer. In three of the five patients there was an additional risk factor present such as smoking or diabetes mellitus. In all five patients no major complication due to marginal perfusion of the contralateral side of the flap was encountered. In two patients there was minor breakdown of fatty tissue that was managed conservatively in both cases. In-flap microvascular augmentation of DIEP-flaps is a valuable tool for the plastic surgeon in microvascular breast reconstruction. It permits usage of the lower abdominal tissue even if perfusion is compromised due to midline scarring. We recommend this technique as a safe alternative in patients seeking autologous breast reconstruction in the presence of a midline abdominal scar.     

Local Inflammation in Rat Dorsal Root Ganglion Alters Excitability and Ion Currents in Small-diameter Sensory Neurons

Background: Chronic pain conditions may result from peripheral nerve injury, chronic peripheral inflammation, or sensory ganglia inflammation. However, inflammatory processes may also contribute to peripheral nerve injury responses. To isolate the contribution of local inflammation of sensory ganglia to chronic pain states, the authors previously developed a rat model in which long-lasting pain is induced by inflaming sensory ganglia without injuring the neurons. This results in prolonged mechanical pain, local increases in proinflammatory cytokines, increased neuronal hyperexcitability, and abnormal spontaneous activity.

Methods: The authors used whole cell patch clamp in acutely isolated small-diameter neurons to determine how localized inflammation (3-5 days) of L4 and L5 ganglia altered voltage-gated K+ and Na+ currents.

Results: Tetrodotoxin-sensitive Na+ currents increased twofold to threefold in neurons from inflamed ganglia. Tetrodotoxin-resistant Na+ currents increased more than twofold, but only in cells that bound isolectin B4. These increases occurred without shifts in voltage dependence of activation and inactivation. Similar results are seen in models of peripheral inflammation, except for the large magnitudes. Unlike most pain models, localized inflammation increased rather than decreased voltage-gated K+ currents, due to increased amplitudes of the sustained (delayed rectifier) and fast-inactivating transient components. The overall effect in current clamp experiments was an increase in excitability as indicated by decreased rheobase and lower action potential threshold.     

Immediate and delayed cord clamping in infants born between 24 and 32 weeks: a pilot randomized controlled trial.

OBJECTIVE: This pilot study's aim was to establish feasibility of a protocol for delayed cord clamping (DCC) versus immediate cord clamping (ICC) at preterm birth and to examine its effects on initial blood pressure and other outcomes. STUDY DESIGN: A randomized controlled trial recruited 32 infants between 24 and 32 weeks. Immediately before delivery, mothers were randomized to ICC (cord clamped at 5 to 10 seconds) or DCC (30- to 45-second delay in cord clamping) groups. RESULTS: Intention-to-treat analyses revealed that the DCC group were more likely to have higher initial mean blood pressures (adjusted OR 3.4) and less likely to be discharged on oxygen (adjusted OR 8.6). DCC group infants had higher initial glucose levels (ICC=36 mg/dl, DCC=73.1 mg/dl; p=0.02). CONCLUSION: The research design is feasible. The immediate benefit of improved blood pressure was confirmed and other findings deserve consideration for further study.     

Überbrückende Antikoagulation

Patients on anticoagulants of the vitamin K antagonist type may sometimes be scheduled for invasive procedures or surgical operations. In order to minimize the risk of thromboembolism caused by the interruption of chronic anticoagulation for the procedure, temporary administration of anticoagulants with shorter half-lives is required (so-called bridging anticoagulation). The present review outlines the spectrum of risks during this period regarding both thromboembolism and major bleeding. Low molecular weight heparins may be considered the medication of choice for bridging anticoagulation, mainly for practical reasons. Since they require no coagulation monitoring or dose adjustment, outpatient treatment is feasible. Such heparins are not labelled for the indication of bridging anticoagulation. However, based on recent studies of large patient cohorts, evidence of their efficacy and safety is significantly more solid than for unfractionated heparin. A simple dosing scheme for low molecular weight heparins is given here and all requirements are discussed for safe guidance through episodes of bridging anticoagulation.     

Providence School Asthma Partnership: School-based Asthma Program for Inner-City Families

Over 3 years, 972 families participated in an after-school asthma program at their child's school. Parents and children attended concurrent 2¹/₂ -hour workshops. Parents were 74% Latino; 45% non-English speaking, with 77% of children on Medicaid. Asthma symptoms were significantly reduced, from multiple times per week to less than once per week on average. Oral steroid use decreased to one third of baseline use. Hospital days decreased from 11% to 2%; emergency visits decreased 35% to 4%; and school days missed decreased 48% to 20%. This program has now become sustainable with both private and Medicaid insurance coverage.