Paul S. Malchesky

Apheresis Technologies and Clinical Applications: The 2005 International Apheresis Registry

Abstract:  The developments in apheresis technologies and techniques and their clinical applications worldwide are technologically, sociologically, and economically motivated. In past apheresis surveys the statistics have highlighted both the differences by geographic region in clinical practice and in the types of technologies utilized. While a national view of apheresis is very important, an international view may be more representative overall of this therapeutic modality than national results that are highly dependent on the local economics and the available technologies. These regional differences have provided a basis for scientific and clinical assessment of these apheresis technologies and their clinical outcomes, and have impacted the marketing and business developments of new technologies worldwide. The results of the International Apheresis Registry for 2005 reporting from 22 centers on 5 continents are presented. The survey collected data exclusively via a secure internet website on 1133 patients for a total of 6501 treatments. Unlike our prior registries, information on stem cell infusions was gathered. Information gathered included patient demographics, medical history, treatment diagnoses, treatment specifics (type, methodology, access type, anticoagulants, drugs, and equipment usage), side‐effects, clinical response, and payment provider. As in the prior International Apheresis Registries for 1983, 2000, and 2002 the survey results highlight the regional differences in apheresis usage and treatment methodologies, indicating that an international overview of apheresis may be more representative of the impact of this therapeutic modality.

Prion disease and medical devices.

Prions are novel proteinaceous-infectious agents that have been implicated in transmissible spongiform encephalopathies. It is now generally accepted that noninfectious prion proteins are normally produced by the host and may undergo a conformational change to an abnormal, pathologic form, which appears to be responsible for disease symptoms. Many methods of decontamination and sterilization are claimed to be ineffective against prion proteins. Incidences of iatrogenic transmission of prions due to medical devices have been reported, and the recommended clinical practices when handling suspected cases are reviewed. Recent results with a peracetic acid based sterilant indicate that it may be a safe and effective means of prion inactivation on medical devices.

Extracorporeal Techniques of Endotoxin Removal: A Review of the Art and Science

The incidence of sepsis in the United States has risen in the past few years, and mortality from sepsis has risen over the past several decades. These increases have occurred despite the progress made in antibiotic therapy. The high mortality rate may not be related to the bacteria themselves but rather to the hosts response. Of particular concern is the bacterial release of endotoxins, the development of endotoxic shock, and the resulting multiorgan failure, which has a high fatality rate and is the leading cause of death in patients admitted to intensive care units. Removing or neutralizing endotoxins are the two major therapeutic approaches to treating sepsis. To date, pharmacological methods have not been successful. Extracorporeal techniques are based on filtration, sorption, or both. Results with hemofiltration have not been definitive, in part because endotoxin levels have not been measured. Sorption devices, based on polymyxin B and anion exchange matrices, do remove endotoxins. Clinical studies in Japan on septic shock or multiorgan failure with polymyxin-B-bound fibers in direct hemoperfusion continue to suggest the utility of extracorporeal techniques for endotoxin removal. Continued effort is required and warranted to assess the clinical efficacy of these techniques.

Quantitative separation of bacteria in saline solution using lanthanide Er(III) and a magnetic field

A trivalent lanthanide ion, erbium (Er3+), has been used in combination with a magnetic separation technique to isolate seven bacterial species from suspensions in 0.9% saline. Erbium has an exceptionally high atomic magnetic moment of 9.3 Bohr magnetons, and following addition as ErCl3 (final concentration 5 mM) to bacterial suspensions, it imparts the magnetic moment to the bacterial cells by ionic binding to the cell surface. Strains of Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa, Staphylococcus epidermidis, Staphylococcus saprophyticus and Enterococcus faecalis were obtained from the Quality Control Depository of The Cleveland Clinic Foundation, Cleveland, Ohio, USA as suspensions in 0.9% NaCl, in concentrations ranging from 10(2) to 10(8) c.f.u. ml-1. Bacteria were separated from solution inside a capillary flow cell exposed to a highly non-homogeneous magnetic field (maximum field intensity was 0.4 T) and quantified by a light scattering method. The quantity of cellular deposition in the magnetic field was correlated with the initial concentration of cells in the suspension, expressed in c.f.u. ml-1, and sample volume (1.5 and 3.0 ml), sample pH (prior to ErCl3 addition), affinity to Gram stain (negative vs positive) and species.(ABSTRACT TRUNCATED AT 250 WORDS)

Membrane plasma separation and the on-line treatment of plasma by membranes

Abstract The application of membranes for the separation of solids from liquids is quite common in industrial processes and has had a major impact on biomedical processes. Biomedical applications of blood processing range from the use of large-pore structures for filtration of blood for the removal of large particles (> 20 μm) (transfusion filters) to membranes for the dialysis of blood for the removal of low molecular weight solutes in the treatment of renal failure. Within the past decade membranes have been applied in the separation of plasma from whole blood. Compared to centrifugal plasma separation membrane plasma separation is preferred when used with on-line plasma fractionation since the plasma is free of cells. Also, membranes have been applied in the on-line treatment of the plasma for the selective removal of macromolecules in selected disease states obviating the need for plasma replacement products. The membranes for plasma separation and fractionation may be distinguished from conventional dialysis membranes and high-flux membranes used in hemofiltration by their very high or select passage of plasma proteins. Membrane techniques are simple and safe to apply and can be competitive to other separation technologies. Studies of membranes in the separation of components from the complex mixture of blood and their use in the separation of macromolecules in plasma are particularly useful in extending the applications of membranes in bioseparations.

Therapeutic trial of cryofiltration in patients with rheumatoid arthritis

Cryofiltration, a new technique for on-line plasma separation and its treatment by cold filtration, enables the selective removal of immune complexes and eliminates the need for replacement proteins. Fifteen patients with rheumatoid arthritis were treated for nine to 10 consecutive sessions over a three- to five-week period. Circulating immune complexes decreased by an average of 78 percent and rheumatoid factor by 32 percent. This was accompanied by significant clinical improvement in morning stiffness, articular index, 50-foot walking time, grip strength, and target joint circumference. Cryofiltration might thus be beneficial for a subgroup of rheumatoid arthritis patients in whom conventional therapy has failed.

Reprocessing of reusable medical devices.

Advances in medical science and, in particular, minimally invasive surgical and diagnostic procedures have stimulated the development of new and improved medical devices. This has been made possible because of developments in engineering and material sciences. The design of devices for reusability is particularly important in an effort to provide cost effective healthcare. Concerns and issues include the ability to safely and effectively reprocess the devices, infection prevention and control, safety of the patient and healthcare worker, environmental concerns, and effective use of resources. From an infection prevention point of view, present requirements are based upon the intended use of the devices. Critical devices require sterilization. Semi-critical devices require, as a minimum, high level disinfection. Sterilization is, however, preferred whenever possible. Before sterilization or disinfection, devices should be cleaned adequately. Device designs should be readily amenable to cleaning and sterilization. In the past, design requirements focused primarily on the clinical user and device functionality, with reuse considerations left to the user. In the current market, the customer is redefined and, for reusable medical devices, includes all those associated with the device through the reprocessing procedure. In addition, regulations require that manufacturers give detailed instructions for reprocessing medical devices. The device users have the obligation to follow reprocessing instructions. Many choices exist today in device designs, including disposable or reusable devices. The user needs to balance cost versus convenience and reprocessing requirements for reusables. Current trends are to reuse more devices, including many of which were meant to be disposable. Cost effective designs can best be achieved when the user and manufacturer work together on the design.(ABSTRACT TRUNCATED AT 250 WORDS)

Modification of ferrography method for analysis of lymphocytes and bacteria

Abstract Problems associated with the analysis of low magnetically susceptible or diamagnetic biological particles in ferrography are related to the unoptimal fluid dynamics, the low magnetic field strength and gradients and the lack of effective magnetizing agents. Flow geometry optimization in slide ferrography has been undertaken with the specific aims of obtaining a thinner flow channel, better-defined fluid flow geometry, uniform distribution of particles within the flowing volume, containment of the flowing liquid sample, exposure of all flowing particles to the magnetic field, and differentiation of deposition layers formed by different forces, i.e. magnetic, gravitation and flow related. These specific aims were attained by adopting a novel slide scheme which at present reduces the fluid flow thickness by tenfold and increases the peak relative magnetostatic force by up to three orders of magnitude, compared with the conventional slide ferrography. The novel slide ferrography scheme, combined with the use of the strongest permanent magnet available, is better suited to the analysis of biological particles than conventional ferrography is. Where native mononuclear blood cells showed no response to the magnetic field when treated with erbium, mononuclear cells which had been cultured for as short as 24 h and as long as 72 h show magnetically induced deposition after erbium treatment. Non-specific labeling with cationized ferritin causes the magnetic deposition of all cells studied, i.e. native and cultured human lymphocytes, and mouse lymphoma cells (YAC-1). Modified slide ferrography shows that the bacterium Escherichia coli has a high affinity for erbium ions and becomes readily magnetized and separated. Observations of bacterial magnetic deposition are possible in unstained slide mounts using scattered light. Scattered-light intensity correlated with the bacterial cell concentration in the samples analyzed by ferrography.

Are selective macromolecule removal plasmapheresis systems useful for autoimmune diseases or hyperlipidemia

Although technical limitations exist with existing selective removal systems, very few products are available and no major clinical trials have demonstrated the superiority or equivalence of selective removal systems over plasma exchange. It is generally recognized that selective removal systems are preferable, and that selective macromolecule removal plasmapheresis systems are useful for autoimmune diseases or hyperlipidemia. In the treatment of a disease with a selective removal device, the disease pathogen should be identified and the efficacy of removal demonstrated. In general, for plasmapheresis applications, there is a need to better understand the pathophysiology of the disease states and to identify the pathogenic molecules. With such information, development of the optimal selective removal method will be possible. There is the need for clinical studies to compare selective removal and plasma exchange for specific disease states. Incentives for the development of improved selective removal technologies where cost effectiveness could be demonstrated should be encouraged.

Removal of Protein-Bound Toxins from Critical Care Patients

AbstractThe coma which develops during acute hepatic failure has been attributed to the accumulation of toxic metabolites, since coma is potentially fully reversible without residual sequelae and there are no important structural changes in the brain of these patients [1]. Removal of these toxins might accelerate arousal and thereby improve survival by preventing cerebral edema and other complications of coma. Ultimately these complications are often the cause of death in many instances of acute hepatic failure, even in patients whose livers are beginning to regenerate [2].