Comparison of the efficacy of IGIV-C, 10% (caprylate/chromatography) and IGIV-SD, 10% as replacement therapy in primary immune deficiency. A randomized double-blind trial

A novel method of large-scale chromatography has been developed to improve recovery and purity of immunoglobulin G (IgG) from pooled plasma. The current study compares safety, toxicity and efficacy of two intravenous immunoglobulin products: a novel formulation, IGIV caprylate/chromatography (IGIV-C; Gamunex, 10%) and a licensed solvent/detergent-treated product, Gamimune N, 10% (IGIV-SD). The study, a randomized, double-blind, parallel group, therapeutic equivalence trial, was conducted at 25 treatment centers in Canada and the United States. Patients (n=172) having confirmed chronic primary immunodeficiency (PID), aged 1-75 years, and receiving IGIV therapy were enrolled. For 9 months, patients were treated with IGIV-C or IGIV-SD in accordance with the patient's individualized treatment regimen utilized before study entry. The primary endpoint was the proportion of patients with >or=1 validated acute sinopulmonary infection during the treatment period. Secondary endpoints included the proportion of patients with all infections, time to first infection, annual infection rates, lung function parameters, infusion-related safety and viral safety. The annual validated infection rate in the IGIV-C group was 0.18 compared to 0.43 in the IGIV-SD group (p=0.023). Nine patients receiving IGIV-C experienced validated infections, compared to 17 patients in IGIV-SD group (p=0.06). Acute sinusitis (validated plus clinically defined) was less frequent in the IGIV-C group (p=0.012). Presence of bronchiectasis did not affect efficacy. Adverse reactions were similar in frequency and severity in both groups. No evidence of viral transmission was observed. IGIV-C appears to be superior to IGIV-SD in preventing validated sinopulmonary infections, especially acute sinusitis, in patients with PID.     

Continuous Measurement of Multiple Inert and Respiratory Gas Exchange in an Anaesthetic Breathing System by Continuous Indirect Calorimetry

A method was tested which permits continuous monitoring from a breathing system of the rate of uptake of multiple gas species, such as occurs in patients during inhalational anaesthesia. The method is an indirect calorimetry technique which uses fresh gas rotameters for control, regulation and measurement of the gas flows into the system, with continuous sampling of mixed exhaust gas, and frequent automated recalibration to maintain accuracy. Its accuracy was tested in 16 patients undergoing pre-cardiopulmonary bypass coronary artery surgery, breathing mixtures of oxygen/air and sevoflurane with/without nitrous oxide, by comparison with the reverse Fick method. Overall mean bias [95% confidence interval (CI)] of rate of uptake was 17.9 [7.3 to 28.5] ml min⁻¹ for oxygen, 0.04 [−0.42 to 0.50] ml min⁻¹ for sevoflurane, 10.9 [−16.1 to 37.8] for CO₂, and 8.8 [−14.8 to 32.4] ml min⁻¹ for nitrous oxide where present. The method proved to be accurate and precise, and allows continuous monitoring of exchange of multiple gases using standard gas analysis devices. Stuart-Andrews C, Peyton P, Humphries C, Robinson G, Lithgow B. Continuous measurement of multiple inert and respiratory gas exchange in an anaesthetic breathing system by continuous indirect calorimetry.     

Defined chemically cross-linked oligomers of human C-reactive protein: characterization and reactivity with the complement system.

Chemically cross-linked C-reactive protein (CRP) oligomers were prepared and characterized, and C1q binding and C activation were investigated. Purified human CRP was polymerized in the presence of both non-cleavable and cleavable cross-linking agents and further separated by Superose 12 analytical FPLC column chromatography into fractions of 110 KDa (pentameric monomers), 220 KDa (dimers) and 330 KDa (trimers); virtually no larger oligomers were formed under a variety of experimental conditions. CRP subunits were cross-linked both within and between CRP pentamers. CRP trimers retained native CRP antigenicity without expression of neo-CRP epitopes. CRP trimers showed maximal binding and CRP dimers showed partial binding of solid phase C1q while CRP monomers bound virtually no C1q at all; CRP trimers also bound to fluid phase C1q. Binding was Ca++ independent and increased as the ionic strength or pH were lowered, characteristics comparable to binding of aggregated IgG to C1q; it was not inhibited by phosphorylcholine. CRP trimers consumed total C, C1 and C2 haemolytic activities upon incubation in fresh human serum, but much less efficiently than did CRP-protamine complexes or Agg-IgG. CRP trimers failed to deplete alternative C pathway haemolytic activity at all. The stable, chemically defined CRP oligomers described in this report, which bind C1q efficiently but display poor ability to activate the classical C pathway in the absence of an appropriate ligand, should be valuable in further studies of the interactions between CRP and the C system.     

Improvement of respiratory compromise through abductor reinnervation and pacing in a patient with bilateral vocal fold impairment

Objectives/Hypothesis.

To determine whether respiratory compromise from bilateral vocal fold impairment (paralysis) can be objectively alleviated by reinnervation and pacing.

Methods.

A patient with paramedian vocal folds and synkinesis had a tracheotomy for stridor after bilateral laryngeal nerve injury and Miller Fisher syndrome. One posterior cricoarytenoideus (PCA) received a nerve‐muscle pedicle fitted with a perineural electrode for pacemaker stimulation. The airway was evaluated endoscopically and by spirometry for up to 1 year.

Results.

Bilateral vocal fold patency during quiet breathing was reversed to active vocal fold adduction during tracheal occlusion. Peak inspiratory flows (PIFs) were significantly higher (P < .001) after reinnervation. PIFs and glottic apertures increased further under stimulation (42 Hz, 1–4 mA, 42–400 μsec). although the differences were not significant.

Conclusions.

Based on our preliminary data, PCA reinnervation and pacing offer promise for amelioration of respiratory compromise after paradoxical adduction in bilateral vocal fold impairment. Laryngoscope, 2010     

Ultrasound of the whole breast utilizing a dedicated automated breast scanner

Innovations in design of a dedicated breast scanner resulted in automation of the scanning process, the production of high resolution images of the whole breast and an efficient mode of image review. The results of clinical evaluation of the prototype of this breast scanner investigating normal breasts as well as benign and malignant breast lesions are presented.     

Incompatibility of contrast agents with intravascular medications. Work in progress

In vitro and in vivo precipitation of iodinated contrast agents when ioxaglate and papaverine are given together has been reported. To verify these reports and to investigate other medications not previously tested, the authors analyzed mixtures of contrast agents and medications in vitro with a light spectrophotometer and observed them for visible precipitates for up to 120 minutes. Previously reported incompatibilities between ionic or low-osmolality contrast media and medications were verified, and several new incompatibilities were discovered. No incompatibilities were found when the drugs tested were mixed with the new nonionic contrast media.     

Manipulation: investigation of a proposed mechanism

The purpose of this study was to investigate whether spinal manipulation alters the posteroanterior stiffness of the manipulated region. Thirty subjects with no history of thoracic pain or contraindication to manipulation participated. The manipulation studied was a posteroanterior thrust applied to the T_4–5 spinal level. The effect of the manipulation was compared to a control intervention of supine lying. The posteroanterior stiffness of all subjects was measured at the T₄ and T₅ levels initially, and remeasured after both the manipulation and control interventions. Change scores relating to the change in posteroanterior stiffness due to manipulation and due to the control intervention were computed. A t-test comparing the change scores between interventions revealed no significant difference. However, the posteroanterior stiffness at T₅ was found to be significantly greater than at T₄. It was concluded that in the case of asymptomatic subjects these results did not provide support for the hypothesis that posteroanterior stiffness is altered by manipulation.     

Maintenance of morphology and function of mixed liver cell spheroids under collagen gel environment

Mixed liver cell spheroids from rats consisting of hepatocytes and nonparenchymal cells lose three-dimensional structure and function when cultured on dishes. In order to maintain the configuration and function of the spheroids, we cultured them with collagen gel in various conditions, such as on the surface of collagen gel (group 2), between two collagen gel layers (group 3), and within collagen gel (group 4). Spheroids cultured on a standard collagen-coated dish were used as controls (group 1). Culture was continued for 10 days. Phase-contrast microscopy revealed that the spheroids of group 1 lost their spheroidal configuration and became a monolayer within 24 h. Group 2 spheroids also spread out to a monolayer, but thus occurred at 24 to 48h. In group 3, spheroid configuration was sustained until day 10, though slightly flattened. In group 4, the spheroid configuration was well maintained throughout the culture period. Urea synthesis of the spheroids cultured with collagen gel was significantly higher than in group 1 between days 1 and 3. Albumin synthesis of three experimental groups was also significantly higher than that of group 1. Although three experimental groups showed no difference in urea synthesis, albumin production by spheroids in groups 3 and 4 was better maintained than in group 2, even toward the end of the culture period. It is concluded that mixed liver-cell spheroid culture within collagen gels showed better maintenance of their configuration and function.