Antepartum prediction of the postmature infant.

A prospective investigation was undertaken to determine whether present antepartum methods of fetal assessment were useful in predicting postmaturity. Thirty-two (22%) of 147 strictly defined postdate pregnancies produced infants with signs of postmaturity. Clinical findings, fetal heart rate testing (primarily nonstress tests), and fetal movement charting were not found to be reliable predictors. Single-voiding estrogen:creatinine (E:C) ratios were significantly (P less than .0001) lower in fetuses with subsequent findings of postmaturity than in those without such signs, and all subnormal values were associated with postmature infants. Twenty-four of 29 pregnancies with oligohydramnios diagnosed by ultrasonography produced postmature infants, whereas 110 of 118 pregnancies with either pockets or an adequate volume of amniotic fluid produced infants who were not postmature. Of the fetal surveillance methods used in the authors' clinic, subnormal E:C ratios and ultrasonic evidence of oligohydramnios were the most reliable predictors of postmaturity.

A randomized double-blind sham-controlled trial of the Prosorba column for treatment of refractory rheumatoid arthritis.

The Prosorba column has been studied as a novel therapy for rheumatoid arthritis in several clinical settings over the last 5 years. In this article, we summarize the pivotal clinical trial study supporting the safety and efficacy of the Prosorba column as it is applied to treatment of rheumatoid arthritis. The Prosorba column is a medical device that contains purified staphylococcal protein A covalently bound to a silica matrix. This device is used to treat patient plasma in conjunction with a plasmapheresis machine. In this ex vivo treatment, blood is withdrawn from the patient, cells are separated from plasma in the machine, and the plasma is passed through the Prosorba column. The plasma then is recombined with the cells and returned to the patient. The Prosorba column was approved for the treatment of idiopathic thrombocytopenic purpura in 1987 and, in 2 open-label trials (1,2), showed promising evidence of efficacy in rheumatoid arthritis. A subsequent Phase 3 pivotal trial demonstrated statistical superiority of Prosorba treatments to sham column apheresis (3). Analysis of the pivotal trial of patients who completed all treatments indicated that 41.7% of the Prosorba treated patients met American College of Rheumatology defined response criteria as compared to 15.6% of the sham treated patients. This difference was significant at a level of p < or = 0.02.

Blood-surface interactions: Fourier transform infrared studies of protein surface adsorption from flowing blood plasma and serum.

The adsorption of blood proteins onto various surfaces in contact with flowing blood plasma or serum has been investigated using Fourier Transform infrared spectroscopy (FT-IR) coupled with attenuated total reflection (ATR). Comparison of adsorption from a static versus a flowing blood plasma system indicated that a greater amount of protein was adsorbed when the static system was employed, but desorption was observed with the static system and not in the flowing system. When plasma and serum were compared in terms of amount and type of protein adsorbed, little difference was noted in either kinetics of adsorption or stability of the adosrbed layers. Variations in the ratios of infrared adsorption bands (from either plasma or serum) indicate that changes occur during the adsorption process in the protein layers. A comparison of poly(vinyl chloride) to germanium as the protein adsorbing surface in the static system showed differences in terms of the composition of the adsorbed layers.

Blood plasma/implant interfaces FT--IR studies of adsorption on polyethylene and heparin-treated polyethylene surfaces.

Described is an attenuated total reflection (ATR), Fourier Transform infrared (FT--IR) technique useful for studying the adsorption of blood plasma proteins onto polymer surfaces. This technique had the advantage of employing whole blood plasma and has detected differences between the species adsorbed onto heparin-treated polymers as compared to the species adsorbed on untreated polymers. Differences detected consist of 1) changes in conformation and/or composition of proteins adsorbed on treated and untreated polymers, and 2) changes in amounts of carbohydrate-containing materials on the treated and untreated polymer surfaces. The advantages of FT-IR are its extreme sensitivity and its ability to work with highly complex systems such as whole blood plasma. These abilities should be of great value for providing direct molecular level information concerning protein adsorption from intact blood systems.

Quantitative surface studies of protein adsorption by infrared spectroscopy. I. Correction for bulk concentrations.

A method for correcting attenuated total reflectance (ATR) infrared spectra of surface-adsorbed proteins for the contribution of proteins in the bulk solution has been demonstrated. This procedure estimates the soluble protein contribution to the ir spectra from parameters determined from transmission experiments, and uses the absorbance of the water band in ATR as an internal reference. Based on this procedure, the soluble protein contribution to the total spectrum is estimated to range from approximately 3% for IgG or albumin in solution at 1 mg/ml, to approximately 35% when whole blood (from sheep) is adsorbed onto a 45 degrees germanium ATR crystal.

Immunoadsorption for the treatment of rheumatoid arthritis: final results of a randomized trial. Prosorba Trial Investigators.

A double-blind, randomized, placebo controlled study was conducted to determine the efficacy of a promising immunoadsorption treatment device containing staphylococcal protein A (Prosorba Immunoadsorption Column, Cypress Bioscience, Inc., San Diego, CA, U.S.A.) in patients with refractory rheumatoid arthritis (RA). Eligibility criteria required adult RA patients who had failed either methotrexate or 2 other disease modifying antirheumatic drugs (DMARD) and who had predefined active disease. All disease-modifying agents were discontinued at least 30 days prior to entry. Patients received 12 weekly procedures after being randomized to the active treatment arm or to the sham treatment arm (apheresis only). Evaluations were double-blinded and occurred at baseline and periodically for 24 weeks thereafter. Primary efficacy was assessed at 7 and 8 weeks after the completion of 12 treatments (at trial Weeks 19 and 20) using the American College of Rheumatology (ACR) definition of improvement (1,2), and results from the assessments at Weeks 19 and 20 were averaged. Ninety-nine randomized patients had a mean disease duration of 15.4 years and received an average of greater than 5 DMARD regimens prior to entry. Analysis of patients who completed all treatments and follow-up indicated that 15 of 36 (41.7%) column-treated patients responded compared to 5 of 32 (15.6%) sham-treated patients (p < or = 0.003). Intent to treat analysis of all patients who were randomized in the study indicated 15 of 52 (28.9%) column-treated patients responded compared to only 5 of 47 (10.6%) patients who received sham treatments (p = .005). Common adverse events (AEs) included joint pain, fatigue, joint swelling, and hypotension. Central line usage was clearly associated with significant AEs during this trial and is not recommended. Hemoglobin, hematocrit, and mean corpuscular volume values decreased similarly in both treatment arms, attributed to phlebotomy for laboratory and scientific studies and to small, repetitive (normal) apheresis losses. Other AEs such as nausea, rash, pruritus, flushing, and fever occurred in 1 to 6% of treatments in each arm (NS). There was no significant increase in AEs in column-treated patients compared to sham-treated patients. Protein A immunoadsorption was proven to be a new therapeutic alternative in patients with severe, refractory disease.

Quantitative surface studies of protein adsorption by infrared spectroscopy. II. Quantification of adsorbed and bulk proteins.

Attenuated total reflectance Fourier transform infrared spectra of surface-adsorbed proteins are correlated with concentration measurements determined by 125I-labeled proteins. This paper demonstrates that linear correlations between the intensity of the major bands of proteins and the quantity of proteins can be obtained for human albumin and immunoglobulin G up to surface concentrations of approximately 0.25 microgram/cm2. A poorer correlation was observed for human fibrinogen. A linear correlation was also observed between the concentration in the bulk solution and the major bands of albumin up to a concentration of 60 mg/ml.

IR spectral changes of bovine serum albumin upon surface adsorption.

The adsorption of bovine serum albumin from flowing solutions onto germanium and three polyetherurethanes varying in soft segment content was studied by a Fourier transform infrared/attenuated total reflectance technique. Spectral differences observed in the amide I, II, and III regions upon adsorption to all four surfaces were consistent with a loss of helix and gain of beta-structure. There appeared to be a slight difference between BSA adsorbed to germanium and the PEUs, but no distinction could be made between BSA adsorbed to the different PEUs.

A pilot study using a staph protein A column (Prosorba) to treat refractory rheumatoid arthritis.

OBJECTIVE: To assess the safety and effectiveness of extracorporeal treatments with protein A (Prosorba) columns in the treatment of patients with severe refractory rheumatoid arthritis (RA) in an open label pilot study. METHODS: Fifteen patients with RA who had failed to respond to 2 or more disease modifying antirheumatic drugs were "washed out" for 1-3 months before enrollment into this 6 month pilot study. The treatment schedule called for patients to receive apheresis treatments across staphylococcal protein A columns once a week for 12 weeks. Clinical evaluations of RA activity, defined by Paulus criteria, were conducted at study enrollment (baseline) and monthly throughout the treatment phase. In addition, examinations were conducted at 2, 4, 8, and 12 weeks after the last treatment. Fourteen patients received all 12 scheduled treatments, while one patient received only 10 treatments due to complications secondary to pneumonia. RESULTS: Using Paulus 50% criteria, 9 of 15 (60%) patients were improved at the 4th month, and one more fulfilled >20% Paulus criteria (7%) in the 5th month after starting therapy. The study group reported an average of 2.47 adverse effects per treatment, of which the most common were joint pain and swelling and fatigue of short duration (arthritic flare). CONCLUSION: The adverse effects associated with this apheresis based treatment proved to be manageable and of short duration and resolved without sequelae. The results suggest that extracorporeal protein A therapy may have a role in the management of refractory RA, and encouraged the initiation of a larger, blinded, controlled clinical trial.

The Prosorba column for treatment of refractory rheumatoid arthritis: a randomized, double-blind, sham-controlled trial.

OBJECTIVE: To evaluate the efficacy and safety of the Prosorba column as a treatment for rheumatoid arthritis (RA) in patients with active and treatment-resistant (refractory) disease. METHODS: A sham-controlled, randomized, double-blind, multicenter trial of Prosorba versus sham apheresis was performed in patients with RA who had failed to respond to treatment with methotrexate or at least 2 other second-line drugs. Patients received 12 weekly treatments with Prosorba or sham apheresis, with efficacy evaluated 7-8 weeks after treatment ended. Patients were characterized as responders if they experienced improvement according to the American College of Rheumatology (ACR) response criteria at the efficacy time point. A data safety monitoring board (DSMB) evaluated interim analyses for the possibility of early completion of the trial. RESULTS: Patients in the trial had RA for an average of 15.5 years (range 1.7-50.6) and had failed an average of 4.2 second-line drug treatments prior to entry. After the completion of treatment of 91 randomized patients, the DSMB stopped the trial early due to successful outcomes. Of the 47 patients in the Prosorba arm, 31.9% experienced ACR-defined improvement versus 11.4% of the 44 patients in the sham-treated arm (P = 0.019 after adjustment for interim analysis). When results from 8 additional patients, who had completed blinded treatments at the time of DSMB action, were added to the analysis (n = 99), results were unchanged. The most common adverse events were a short-term flare in joint pain and swelling following treatment, a side effect that occurred in most subjects at least once in both treatment arms. Other side effects, although common, occurred equally as frequently in both treatment groups. CONCLUSION: Apheresis with the Prosorba column is an efficacious treatment for RA in patients with active disease who have failed other treatments.