Conservation of receptor antagonist anti-tumor activity by epidermal growth factor receptor antibody expressed in transgenic corn seed

Recombinant protein production in plants such as corn is a promising means to generate high product yields at low comparable production cost. The anti-EGFR monoclonal antibody C225, cetuximab, is a well-characterized receptor antagonist antibody recently approved for the treatment of refractory colorectal cancer. We initiated a study to test and compare the functional activity of glycosylated and aglycosylated C225 produced in stable transgenic corn seed. Both corn antibodies were shown to be functionally indistinguishable from mammalian-derived C225 in demonstrating high-affinity binding to the EGF receptor, blocking of ligand-dependent signaling, and inhibiting cell proliferation. In addition, consistent with cetuximab, both corn antibodies possessed strong anti-tumor activity in vivo. Acute dose primate pharmacokinetic studies, however, revealed a marked increase in clearance for the glycosylated corn antibody, while the aglycosylated antibody possessed in vivo kinetics similar to cetuximab. This experimentation established that corn-derived receptor blocking monoclonal antibodies possess comparable efficacy to mammalian cell culture-derived antibody, and offer a cost effective alternative to large-scale mammalian cell culture production.     

The Wheelchair Circuit: Construct validity and responsiveness of a test to assess manual wheelchair mobility in persons with spinal cord injury

OBJECTIVE: To assess the validity and responsiveness of the Wheelchair Circuit, a test to assess manual wheelchair mobility in persons with spinal cord injury (SCI). DESIGN: Longitudinal. Subjects performed the Wheelchair Circuit at the start (T1) and at the end (T3) of inpatient functional rehabilitation. Construct validity and responsiveness were assessed. SETTING: Eight rehabilitation centers in the Netherlands. PARTICIPANTS: Seventy-four subjects with SCI admitted for inpatient rehabilitation. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The Wheelchair Circuit consists of 8 wheelchair skills and results in 3 test scores: ability, performance time, and physical strain. The construct validity of the Wheelchair Circuit was assessed by testing whether the test scores were significantly related to the subjects' functional status, physical capacity, lesion level, motor completeness of the lesion, and age. To prove the test's responsiveness, it was assessed whether the test scores had significantly improved between T1 and T3. RESULTS: For construct validity, 4 of the 5 hypotheses were confirmed. For test responsiveness, all 3 test scores had significantly improved during rehabilitation, and the standardized response mean values ranged from 0.6 to 0.9. CONCLUSIONS: The Wheelchair Circuit is a valid and responsive instrument with which to measure manual wheelchair mobility in subjects with SCI.     

Can noncontact mapping distinguish between endo- and epicardial foci?

Objectives  Noncontact mapping has been demonstrated to facilitate RF ablation of ventricular arrhythmias, but the reproducibility in the localization of endocardial exit sites during focal ventricular tachycardia (“VT”) originating from defined myocardial layers has not been systematically studied. Furthermore, it remains unclear whether noncontact mapping can distinguish between endo- and epicardial foci. Methods  In six dogs, constant pacing was applied through octopolar needle electrodes in the left ventricle to mimic VT of subendocardial, midmyocardial (mid1; mid2) or subepicardial origin. Using noncontact mapping, the site of origin was determined for each of 50 consecutive beats of all “VTs” and the variation between respective exit sites was measured. Exit sites were reconstructed for 50 consecutive beats of each “VT” and the time span between site of origin and exit site was measured as a parameter of intramural conduction. Results  While subendocardial and midmyocardial (mid1, mid2) foci were pinpointed with a variation of ≤2 mm, a variation of 4 mm was encountered for subepicardial foci. A gradual increase in intramural conduction was evident from endocardial towards epicardial foci, with significant differences between subendocardial (4.8 ± 0.9 ms), midmyocardial (mid1 = 11.1 ± 4.6 ms; mid2 = 11.8 ± 3.5 ms) and subepicardial (16.8 ± 3.6 ms) foci (P < 0.005). Systematic differences in the morphology of virtual waveforms depending on the site of origin could not be detected. Conclusions  Except for subepicardial foci, noncontact mapping localized focal activity in the LV with high reproducibility. In contrast to morphological parameters, the determination of intramural conduction provides a fair estimate of the depth of foci and is proposed as a novel parameter to identify a subepicardial origin. Dr. Frederik Voss and Dr. Alexander Bauer contributed equally to this work.     

A case report of transverse testicular ectopia with testicular microlithiasis

Transverse testicular ectopia is a rare congenital anomaly in which both testes migrate along the same inguinal canal toward the scrotum. This report describes the case of the rarest form of transverse testicular ectopia in a 23‐year‐old man with coexisting testicular microlithiasis in one of the two testes as diagnosed on sonography and confirmed on MRI. We are unaware of any previous published reports of this association. Although the etiology of both conditions is debatable, each is believed to be associated with an increased risk of testicular malignancy, and this poses a dilemma for the future management of this patient. © 2014 Wiley Periodicals, Inc. J Clin Ultrasound 43:520–523 2015     

Managing oral anticoagulation therapy: improving clinical outcomes. A review

Many physicians are reluctant to prescribe oral anticoagulation therapy (OAT) because of the fear of haemorrhagic complications. Changes in patient health, lifestyle or diet and other drugs can alter the effectiveness of oral anticoagulants. These potential interferences, added to the fact that each individual has a different reaction to these drugs, requires that therapy is monitored regularly. This article aims to review those strategies which help to achieve optimal anticoagulation control and improve the outcomes of OAT. Relevant articles were identified through a search of MEDLINE and included publications reporting on intensity of anticoagulation, the initiation of therapy and the role of pharmacogenetics, the transition from primary to secondary care, management by specialized clinics using decision support software and home‐testing. Implementation of these strategies would increase the use of oral anticoagulants by physicians and offers the potential to improve patient safety and reduce adverse events.