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Biomedical subjects

N Kossovsky

Publications and source records attributed to N Kossovsky.

18 recordsLinked to original sources

Sterically stabilized liposomes. Reduction in electrophoretic mobility but not electrostatic surface potential.

The electrophoretic mobility of liposomes containing a negatively charged derivative of phosphatidylethanolamine with a large headgroup composed of the hydrophilic polymer polyethylene glycol (PEG-PE) was determined by Doppler electrophoretic light scattering. The results show that this method is improved by the use of measurements at multiple angles to eliminate artifacts and that very small mobilities can be measured. The electrophoretic mobility of liposomes with 5 to 10 mol% PEG-PE is approximately -0.5 mu ms-1/Vcm-1 regardless of PEG-PE content compared with approximately -2 mu ms-1/Vcm-1 for similar liposomes but containing 7.5% phosphatidylglycerol (PG) instead of PEG-PE. Measurements of surface potential by distribution of an anionic fluorescent probe show that the PEG-PE imparts a negative charge identical to that by PG, consistent with the expectation of similar locations of the ionized phosphate responsible for the charge. The reduced mobility imparted by the surface bound PEG is attributed to a mechanism similar to that described for colloidal steric stabilization: hydrodynamic drag moves the hydrodynamic plane of shear, or the hydrodynamic radius, away from the charge-bearing plane, that of the phosphate moities. An extended length of approximately 50 A for the 2,000 molecular weight PEG is estimated from the reduction in electrophoretic mobility.

Biophysical Phenomena

Fourier transform infrared spectroscopic analysis of organic oil mastitis.

The prevalent use of "medical grade" silicone oils, gels, and elastomers in medical practice has largely obscured the fact that other (illicit) materials also are still in use. Injection fluids used for tissue augmentations are sometimes composed of adulterated silicone oil formulations containing a variety of organic oils. The differential diagnosis between silicone mastitis and other organic oil mastitis in biopsy and mastectomy specimens cannot be resolved by oral history and histopathologic examination alone. In two of three specimens clinically and histopathologically diagnosed initially as silicone mastitis at the authors' institution, examination by Fourier transform infrared spectroscopy revealed that the principal organic oils were mineral oil and soy or olive oil. Only one specimen of mastitis contained silicone oil. In view of the significant prognostic as well as medicolegal implications of the pathologic diagnosis, the generic term "organic oil mastitis" should be used in the absence of additional objective data.

Female

Mechanism and clinical significance of wear debris-induced osteolysis.

Loosening of joint replacement components is often multifactorial. The quality of initial fixation is very important to the outcome of the arthroplasty and is often a factor in short-term and long-term failure. This paper discusses another important factor of implant loosening, namely wear debris induced osteolysis. Macrophages activated by the phagocytosis of particulate wear debris are the key cells in this process, which can potentially occur in any implant system regardless of implant design or fixation mode. This is because each implant system creates wear debris from the articulating surfaces and the interfaces. The clinical consequences of wear debris cover a broad spectrum from radiolucencies to massive osteolysis and implant failure. For this reason, the reduction of wear debris should be a primary goal of orthopedic research in the future.

Bone and Bones

In vivo characterization of the inflammatory properties of poly(tetrafluoroethylene) particulates.

Suburothelial injections of particulate poly(tetrafluoroethylene) (PTFE) is becoming a widely accepted treatment for a number of urological disorders. Because little is known about the long-term histologic morphology of the injection site, this animal study was performed. Three populations, each consisting of two mongrel dogs, five New Zealand White rabbits, and 10 BALB/c mice, were injected with poly(tetrafluoroethylene) particulate in a glycerine carrier (Polytef Paste) and were followed for a period of 1 week, 3 months, 6 months, and 1 year. Mice received one subcutaneous dorsal injection each, rabbits received two subareolar injections each, and dogs received three subareolar injections each in addition to two periurethral injections. Histologic examination of the biopsy sites revealed a persistent chronic inflammatory reaction with progressive growth of the involved tissue volume. In addition to giant cells and macrophages, lymphocytes became apparent at 3 months and constituted up to 40% of the cellular infiltrate by 1 year. Plasma cells were also noted at the 1-year period in the rabbit model. The progressive growth of the inflammatory pseudo-tumors evoked by injected PTFE may compromise the long-term safety of certain urological procedures involving particulate PTFE.

Acute Disease

Periprosthetic chronic inflammation characterized through the measurement of superoxide anion production by synovial-derived macrophages.

Periprosthetic macrophages were isolated from the synovium of primary and revision arthroplasty patients. Inflammatory activity was determined by the level of superoxide (O2-) production de novo and in response to phorbol myristate acetate (PMA) stimulation. Nonstimulated primary arthroplasty-derived macrophages produced 2.54 +/- 2.04 pmoles of O2-/minute/10(5) cells. When identical reaction tubes were stimulated with PMA, O2- levels increased to 5.76 +/- 3.77 pmol of O2-/minute/10(5) cells. Nonstimulated revision arthroplasty-derived macrophages produced 3.26 +/- 2.02 pmol of O2-/minute/10(5) cells during this ten-minute time period. When identical reaction tubes were stimulated with PMA, O2- levels increased to 3.98 +/- 2.52 pmol of O2-/minute/10(5) cells. The difference in the ratio of O2- production in response to stimulation between primary and revision groups was statistically significant. The observation of a chronic moderate level of activation and the lack of responsiveness to a potent stimulator suggests that macrophage inflammatory activity is down-regulated in periprosthetic synovium.

Adult

Giant cell myocarditis associated with silicone. An unusual case of biomaterials pathology discovered at autopsy using X-ray energy spectroscopic techniques.

Silicones, used extensively in the fabrication of medical devices because they were presumed inert and biocompatible, are now well-recognized inducers of localized granulomatous inflammation. Silicones less commonly are also associated with more complex clinico-pathologic entities. In this communication, the authors present a case of a patient on chronic hemodialysis involving tubing probably fabricated from silicone rubber who died from a giant cell myocarditis associated with silicone rubber. This case is presented to expand the interpretive paradigm of human pathology and underscores the need for pathologists to consider medical-device associated phenomena in the differential diagnosis of clinical specimens.

Aged

Cementless total joint arthroplasty prostheses with titanium-alloy articular surfaces. A human retrieval analysis.

Surgical implants of titanium alloy (Ti-6Al-4V) have been found to be susceptible to abrasive wear, resulting in the well-known phenomenon of metallosis. In the presence of the acrylic debris generated by loose joint arthroplasty prostheses, this abrasive wear is greatly increased. However, the bone loss seen in these cases has generally been presumed to be due to the osteolytic effects of particulate acrylic, not the alloy debris, which has generally been assumed to be biocompatible. To examine the in vivo effects of titanium-alloy wear without the added presence of acrylic debris, a comprehensive analysis was made of cementless human joint arthroplasty prostheses with Ti-6Al-4V alloy surfaces articulating on ultra-high molecular weight polyethylene (UHMWPE). Specimens, including the prostheses, synovium, pseudocapsule and additional soft tissues, and periarticular bone, were retrieved from 22 hips and two knees. Specimens were examined by histologic techniques, energy-dispersive X-ray analysis, and electron microscopy. Serial sections of the implants were evaluated for tissue ingrowth. Tissues surrounding all joints implanted more than one year showed some degree of discoloration indicative of metallosis, whereas after two years the synovium was hypertrophic and villiform. Histologic evaluation showed good fixation by bony ingrowth in the vast majority of cases, although location and extent of ingrowth was dependent on numerous factors. Viability of ingrowth bone was established by fluorochrome labeling. However, despite good biologic fixation, cavitary osteolysis of the bone surrounding the implants was frequently identified. These lesions were filled with sheets of aggressive macrophages within a matrix of fibrous tissue and necrotic debris. Under polarized light the macrophages were found to be filled with alloy and polyethylene fragments of a characteristic size. Osteoblast-mediated remodeling of bone was infrequently observed. Instead, the bone was resorbed along a front in contact with the granulomatous tissues filling the cystic lesions. Visible burnishing was observed on every articular surface, with a linear relationship between wear and time implanted. By one year the surfaces were covered with a characteristic "scratch and gouge" pattern, similar on all sizes of femoral heads as well as the total knee prostheses. This study demonstrates that the combination of Ti-6Al-4V alloy and UHMWPE, when used as a bearing surface combination in total joint arthroplasty prostheses, results in excessive wear of both metal and polymer.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent

Clinical-pathological analysis of failed central nervous system fluid shunts.

Clinical failures of central nervous system fluid shunts remain a vexing problem. Attributed largely to infectious and technical etiologies, it has been hypothesized recently that inflammatory mechanisms may play a role in this clinical phenomenon. In order to obtain morphologic evidence for this hypothesis, a study of failed shunts was performed. Twenty-five of 57 sequentially removed CNS fluid shunt assemblies or components over the course of 18 months contained sufficient intraluminal tissue to allow a histomorphologic assessment. Tissue was removed from either the intraventricular or intraperitoneal portion and examined with routine light microscopical and histochemical techniques to assess the degree of cellularity, composition of the cells, presence of debris, and organisms. Morphologic findings were correlated with the clinical courses and microbiological cultures. Data were analyzed nonparametrically using the chi 2 test. There was a substantially significant association between repeated failures and non-infectious obstructions. Eight demonstrated evidence of active inflammatory processes; and although not statistically significant, the presence in 3 cases of giant cells, macrophages, lymphocytes, and eosinophils all suggestive of a hypersensitivity reaction correlated with the occurrence of culture negative clinical failures. These morphologic findings will stimulate further experimental and clinical research into possible inflammatory mediators of shunt failure.

Adolescent

Hypersensitivity reaction associated with sterile ventriculoperitoneal shunt malfunction.

Infection and obstruction remain significant problems associated with shunts. We studied the clinical and pathological findings in 29 patients who underwent surgical procedures to revise malfunctioning ventriculoperitoneal shunts. The preoperative diagnosis for shunt malfunction was infection in 8 cases, and obstruction in 18 cases. A pathologist NK independently examined the shunt hardware removed from the patients without knowledge of the clinical diagnosis. There were 19 ventricular catheters, 15 valves, and 14 abdominal catheters examined. Fourteen of the patients had had three or more shunt revisions. Three of these patients had evidence of some hypersensitivity reaction due to the shunt hardware (multiple eosinophils and giant cells in tissue enveloping shunt hardware). Of the 15 patients who had two or less shunt revisions, none had evidence of hypersensitivity on pathological examination of the shunt hardware. We conclude that pathological examination of shunt hardware is helpful in understanding noninfectious causes of shunt malfunction. We have identified a subgroup of patients who developed a hypersensitivity-like reaction around the shunt that in certain instances may lead to shunt malfunction. It is important to identify these patients for they may be more likely to have multiple episodes of shunt malfunction.

Adolescent

Temporary microvascular clips.

Selected commercially designated temporary clips (Acland, Biemer, Kleinert-Kutz, Variangle, and Yasargil) were applied for 1 hour to rat common carotid arteries. Scanning electron and light microscopic studies revealed varying degrees of endothelial damage. The authors believe that further improvements are needed in the design of temporary clips.

Animals

Minimum vascular occlusive force.

A mathematical analysis of the minimum occlusion force necessary to occlude small vessels based on the parametric influence of blood pressure, vessel diameter, clamp width, and vessel shape after clamping was performed. The results were confirmed by in vivo experimentation with 60 rat aortas (of 1.8 to 2.4 mm caliber) using a variable-force clamp gauge developed in our laboratory. Experimental and theoretical results differed by only 3 gm. Scanning electron microscopy revealed that the initial changes in the endothelium occurred in smaller radii of curvature. Increased pressure resulted in gross morphological changes across the vessel. The minimum occlusion force (as determined by the variable-force clamp gauge) produced only minimal endothelial damage.

Animals

Effects of contrast media on the canine subarachnoid space.

This study reports an investigation of the canine arachnoid membrane using the scanning electronmicroscope (SEM) regarding the effects of contrast material on these structures. In the normal arachnoid membrane, two basic surface patterns were observed; one fenestrated and the other embossed with parallel fibers. Ventriculography was performed on 30 mongrel dogs divided into five groups: control, air, iophendylate, meglumine iothalamate, and Metrizamide. SEM study of the arachnoid membrane from basal cisterns showed no change after air ventriculography. After contrast agents were used, macrophages appeared and fenestrations became closed with fibrin-like substance.

Air

Scanning electron microscopic anatomy of the supratentorial basal cisterns.

Arachnoid slips from the canine supratentorial basal cisterns were excised and studied by scanning electron microscopy. The inner face of the arachnoid membrane was examined, and two fundamental surface patterns, fenestrated and embossed, were observed. The remaining fibers and microfibers were anchored to these two surface sheets.

Animals