Heating dictates the scalability of CO electrolyzer types.

Electrochemical CO reduction offers a promising method of converting renewable electrical energy into valuable hydrocarbon compounds vital to hard-to-abate sectors. Significant progress has been made on the lab scale, but scale-up demonstrations remain limited. Because of the low energy efficiency of CO reduction, we suspect that significant thermal gradients may develop in industrially relevant dimensions.

Formation and Glomerular Deposition of Immune Complexes in Mice Administered Human Antibodies: Evaluation of Dose, Frequency, and Biomarkers.

Administration of human protein-based drugs to animals often leads to formation of antidrug antibodies (ADAs) that may form circulating immune complexes (CICs) with the dosed protein. Circulating immune complexes can activate and bind complement (cCICs), and if large amount of CICs or cCICs is formed, the clearance mechanism potentially becomes saturated, which can lead to immune complex (IC) deposition and inflammation. To obtain a better understanding of the underlying factors, including the relationship between different dose regimes on IC formation and deposition and identification of possible biomarkers of IC deposition and IC-related pathological changes in kidneys, BALB/c and C57BL/6J mice were administered with human anti-tumor necrosis factor α (aTNFα, adalimumab) or a humanized anti-TNP (aTNP) antibody for 13 weeks.

Antibody-Mediated Neutralization of uPA Proteolytic Function Reduces Disease Progression in Mouse Arthritis Models.

Genetic absence of the urokinase-type plasminogen activator (uPA) reduces arthritis progression in the collagen-induced arthritis (CIA) mouse model to an extent just shy of disease abrogation, but this remarkable observation has not been translated into therapeutic intervention. Our aim was to test the potential in mice of an Ab that blocks the proteolytic capacity of uPA in the CIA model and the delayed-type hypersensitivity arthritis model. A second aim was to determine the cellular origins of uPA and the uPA receptor (uPAR) in joint tissue from patients with rheumatoid arthritis.

Systemic and intestinal levels of factor XIII-A: the impact of inflammation on expression in macrophage subtypes.

Background: Subunit A of coagulation factor XIII (FXIII-A) is important for clot stability and acts in the subsequent wound healing process. Loss of plasma FXIII-A has been reported after surgery, sepsis, and inflammatory conditions. In the intestinal mucosa, FXIII-A is expressed by macrophages and cellular FXIII-A has been associated with phagocytosis and migration of macrophages.

Factor XIII Transglutaminase Supports the Resolution of Mucosal Damage in Experimental Colitis.

The thrombin-activated transglutaminase factor XIII (FXIII) that covalently crosslinks and stablizes provisional fibrin matrices is also thought to support endothelial and epithelial barrier function and to control inflammatory processes. Here, gene-targeted mice lacking the FXIII catalytic A subunit were employed to directly test the hypothesis that FXIII limits colonic pathologies associated with experimental colitis. Wildtype (WT) and FXIII-/- mice were found to be comparable in their initial development of mucosal damage following exposure to dextran sulfate sodium (DSS) challenge.

Journey of a patient with chronic thromboembolic pulmonary hypertension.

Right ventricle (RV) dysfunction is a key outcome determinant and a leading cause of death for patients with chronic thromboembolic pulmonary hypertension (CTEPH). In this report, we followed the 5-year clinical journey of a patient with CTEPH. The tricuspid pressure gradient was significantly increased in the early phase of CTEPH and "normalized" at the late phase of this patient's clinical journey, but this "normalized" gradient is not a positive treatment response but rather an ominous sign of advancing right heart failure owing to an exhaustion of RV contractile function.

A novel B-domain O-glycoPEGylated FVIII (N8-GP) demonstrates full efficacy and prolonged effect in hemophilic mice models.

Frequent infusions of intravenous factor VIII (FVIII) are required to prevent bleeding associated with hemophilia A. To reduce the treatment burden, recombinant FVIII with a longer half-life was developed without changing the protein structure. FVIII-polyethylene glycol (PEG) conjugates were prepared using an enzymatic process coupling PEG (ranging from 10 to 80 kDa) selectively to a unique O-linked glycan in the FVIII B-domain.

Pharmacokinetics and pharmacodynamics of turoctocog alfa and N8-GP in haemophilia A dogs.

The objective of the present study was to evaluate the pharmacokinetic (PK) and pharmacodynamic (PD) profiles of the new recombinant FVIII compound turoctocog alfa and a Glyco-PEGylated FVIII derivative thereof (N8-GP) in Haemophilia A dogs. Six haemophilic dogs divided into two groups were included in the study. Each dog was administered a dose of 125 U kg(-1) , blood samples were collected at predetermined time points for both pharmacokinetic (FVIII measured by one-stage aPTT assay) and pharmacodynamic [whole blood clotting time (WBCT)] evaluations.

Pharmacokinetics and pharmacodynamics of a new recombinant FVIII (N8) in haemophilia A mice.

N8 is a new recombinant factor VIII (rFVIII) compound produced and formulated without human- or animal-derived protein. The aims of the present studies were to evaluate the pharmacokinetics and pharmacodynamics properties of N8 and to compare with a commercially available rFVIII product (Advate(®)) in haemophilia A mice. The pharmacokinetics were evaluated after single i.

Clearance of rFVIIa and NN1731 after intravenous administration to Beagle dogs.

Aim: NN1731 is a recombinant activated factor VII (rFVIIa) analogue with enhanced activity. The objective of the present study was to evaluate the clearance mechanisms of rFVIIa and NN1731 after intravenous administration to Beagle dogs.

Methods: The study was performed in Beagle dogs administered with a single dose of 5.

Monitoring rFVIIa 90 μg kg⁻¹ dosing in haemophiliacs: comparing laboratory response using various whole blood assays over 6 h.

Recombinant FVIIa is a haemostatic agent administered to patients with severe FVIII or FIX deficiency with inhibitors. Although rFVIIa is effective at stopping bleeding, a reliable assay to monitor its effect is lacking. To characterize the pharmacokinetics and global coagulation effects of rFVIIa for 6 h following a IV dose of 90 μg kg⁻¹.

Activation peptides prolong the murine plasma half-life of human factor VII.

Coagulation factors VII (FVII), IX (FIX), X (FX), and protein C share the same domain organization but display very different plasma half-lives. It is plausible that the half-life is influenced by the activation peptide, differing in length and glycosylation and missing in FVII. To test this hypothesis, the influence of activation peptides on the plasma half-life of human FVII was studied by administering human FVII variants containing activation peptide motifs to mice.

Recombinant human factor VIIa (rFVIIa) cleared principally by antithrombin following intravenous administration in hemophilia patients.

Objective: The objective of the present study was to evaluate the pharmacokinetics and the clearance pathways of rFVIIa after intravenous administration to hemophilia patients.

Methods: Ten severe hemophilia patients were included in the study; all patients were intravenously administered a clinically relevant dose of 90 μg kg(-1) (1.8 nmol kg(-1)) rFVIIa.

Intravascular inhibition of factor VIIa and the analogue NN1731 by antithrombin.

NN1731 is a recombinant activated factor VII (rFVIIa) analogue with increased intrinsic activity. This also applies to its reactivity towards antithrombin (AT), the role of which was investigated in a pharmacokinetic (PK) study. NN1731 or rFVIIa was administered to normal and haemophilia A dogs and elimination was measured by FVIIa clot activity, FVIIa- and FVIIa-AT antigen.

Osteophyte formation after multilevel anterior cervical discectomy and fusion causing a delayed presentation of functional dysphagia.

Background Context: Anterior cervical discectomy and fusion (ACDF) is a common procedure used to treat radiculopathy and myelopathy from cervical degenerative disc disease. The complications for this procedure are well known. Dysphagia can occur in the postoperative setting.

Radiotherapy-induced common carotid pseudoaneurysm presenting with initially occult upper airway hemorrhage and successfully treated by endovascular stent graft.

Radiation induced carotid vasculopathy may present as steno-occlusive disease or less commonly as a pseudoaneurysm. The latter most often presents with a pulsatile mass but is a potential cause of life threatening hemorrhage. We present a case of a small common carotid artery (CCA) pseudoaneurysm that was initially dismissed as the cause of the patients presenting epistaxis given its small size and location.

Advances in surgical management of malignancies of the cranial base: the extended transbasal approach.

The extended transbasal approach combines a bifrontal craniotomy with an orbital nasal and potentially a sphenoethmoidal osteotomy to provide excellent access to malignancies of the anterior, middle and posterior skull base. The approach enables the en bloc resection of tumors within the frontal lobes, orbits, paranasal sinuses and sphenoclival corridors without brain retraction and may obviate the need for transfacial access. We present our 7-year experience during which 29 patients underwent surgery with the extended transbasal exposure.

Preoperative radiation therapy and its effects on outcomes in microsurgical head and neck reconstruction.

Objective: Preoperative radiation therapy is considered a significant factor in head and neck reconstruction. STUDY AND DESIGN AND SETTING: In our consecutive series of 114 patients, 44 patients had prior head and neck irradiation. The 2 groups were compared on the basis of age, ischemic time, and flap size and were found not to be statistically different.

Prevalence of penicillin allergy in adults with peritonsillar abscess.

We noticed a seemingly high prevalence of penicillin allergy in patients who had been diagnosed with peritonsillar abscess (PTA) at our institution. To formally investigate this observation, we reviewed the emergency room (ER) records of 118 patients who had presented between Jan. 1, 1995, and Dec.

Phase I study of concomitant chemoradiotherapy with paclitaxel, fluorouracil, gemcitabine, and twice-daily radiation in patients with poor-prognosis cancer of the head and neck.

Purpose: We previously demonstrated high locoregional control, in patients with poor-prognosis head and neck cancer (HNC), using paclitaxel, 5-fluorouracil, hydroxyurea, and concomitant hyperfractionated radiotherapy. In the present phase I trial, gemcitabine, a novel antimetabolite with strong radiation-enhancing activity, replaces hydroxyurea. We sought to determine the recommended phase II dose and clinical efficacy in poor-prognosis HNC patients.

Patterns of failure, prognostic factors and survival in locoregionally advanced head and neck cancer treated with concomitant chemoradiotherapy: a 9-year, 337-patient, multi-institutional experience.

Background: Locoregionally advanced, stage IV head and neck cancer has traditionally carried a poor prognosis. We sought to assess changes in patterns of failure, prognostic factors for recurrence, and overall outcome, using two different strategies of chemoradiotherapy conducted in prospective, multi-institutional phase II trials.

Patients And Methods: Three hundred and thirty-seven stage IV patients were treated from 1989 to 1998.

Surgical variables affecting swallowing in patients treated for oral/oropharyngeal cancer.

Background: Postoperative swallowing function may be influenced by a number of treatment variables; this study examines the relationship of various treatment factors to measures of swallow function.

Methods: Swallowing was examined with the modified barium swallow procedure in 144 patients surgically treated for oral or oropharyngeal cancer 3 months after healing. Univariate and multivariate correlations were used to examine the relationship between swallowing function and treatment.

Neck dissection in the combined-modality therapy of patients with locoregionally advanced head and neck cancer.

Purpose: The purpose of this study was to evaluate the role of neck lymph node (ND) in the combined dissection modality therapy for locoregionally advanced head and neck.

Methods: We identified patients with N2-N3 head and neck cancers who were enrolled in three consecutive multicenter phase II studies of concurrent chemoradiotherapy utilizing 5-fluorouracil and hydroxyurea on an alternate-week schedule with radiotherapy twice daily plus either cisplatin (C-FHX) or paclitaxel (T-FHX). Patients with unknown primary tumors, nasopharyngeal or paranasal sinus primaries, nonsquamous histology, progression or death during therapy, or incomplete therapy were excluded.

Induction chemotherapy followed by concomitant TFHX chemoradiotherapy with reduced dose radiation in advanced head and neck cancer.

Purpose: Induction chemotherapy with carboplatin and paclitaxel followed by concomitant TFHX (paclitaxel, infusional 5-fluorouracil, hydroxyurea, and twice-daily radiation therapy administered every other week) has resulted in 70% 3-year survival in stage IV patients. Locoregional and distant control rates were 94 and 93%, respectively. In an attempt to decrease toxicity without compromising local control, a second cohort of patients was treated with a lower dose of radiation to sites of potential microscopic disease.