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Biomedical subjects

S C Smith

Publications and source records attributed to S C Smith.

At least 181 records · Page 10Linked to original sources

The lining of textured surfaces in implantable left ventricular assist devices. An immunocytochemical and electronmicroscopic study.

OBJECTIVE: The aim was to examine and identify some components of biological linings developed upon the textured surfaces of a circulatory assist device. The development of biological linings upon a textured surface circulatory assist device was evaluated in patients implanted for periods ranging from 84 to 132 days. METHODS: Explanted devices were examined macroscopically. Light microscopy, transmission electron microscopy and immunocytochemistry techniques were employed to evaluate the histogenesis of the tissue deposits upon the device surfaces. Visible material was essentially limited to focal areas upon the static housing and the periphery of the pusher-plate diaphragm (Biomer). RESULTS: Microscopy of the linings showed fibrin-rich areas with platelets, monocytes and few spindle-shaped surface cells. Central areas were composed of multiple layers of spindle-shaped cells separated, mainly, by collagen. Giant-cell foreign-body reaction to Biomer fibrils was seen. CONCLUSION: Transmission electron microscopy and immunocytochemistry indicated the presence of at least two cell populations: fibroblasts and smooth muscle-like cells, or 'myofibroblasts'. There was no evidence of endothelial cell presence.

Adult↗

Clinical safety and cost of heparin titration using bedside activated clotting time.

OBJECTIVE: To evaluate the clinical safety of heparin titration and the procedural cost of anticoagulation measurement using bedside low-range activated clotting time. DESIGN: Quasi-experimental study using data gathered through retrospective record review. SETTING: Coronary care, medical intensive care and telemetry units of a community hospital. SUBJECTS: Sample of 102 patients undergoing elective percutaneous transluminal coronary angioplasty. INTERVENTION: Intravenous heparin therapy was titrated using low-range activated clotting time in 51 percutaneous transluminal coronary angioplasty patients. Data from this group were compared to a matched sample of 51 angioplasty patients whose intravenous heparin therapy was titrated using activated partial thromboplastin time. RESULTS: No differences in procedural, early or late complications were found between the groups. The cost of managing heparin therapy with low-range activated clotting time was less than with activated partial thromboplastin time. CONCLUSION: These results suggest that titrating heparin therapy based on bedside low-range activated clotting time for the angioplasty patients in this sample was as safe as with activated partial thromboplastin time. Use of bedside low-range activated clotting time saved money for the hospital.

Angioplasty, Balloon, Coronary↗

Expression of myosin-class II major histocompatibility complexes in the normal myocardium occurs before induction of autoimmune myocarditis.

Determining how an autoimmune response is initiated is essential to understanding the mechanisms of autoimmunity. Self-reactive T cells, self-protein, and a failure of tolerance to that self-protein are all involved in the pathogenesis of autoimmune disease; yet it is not clear how self-reactive T cells find the target self-protein to initiate an autoimmune response. Although a variety of self-proteins have been shown to be presented on both class I and class II major histocompatibility complex (MHC) molecules, the relationship of these self-proteins to autoimmune disease has not been established. To explore this further, we generated a T-cell hybridoma that recognizes mouse cardiac myosin, the self-protein that induces murine autoimmune myocarditis. Using this hybridoma as a probe to detect myosin-class II MHC complexes, we isolated a class II MHC+/CD45+ residential antigen-presenting cell (APC) population directly from the hearts of normal mice and looked for evidence of endogenous processing of cardiac myosin by these APC. In this report we show that myosin-class II MHC complexes are found on residential APC in the normal mouse heart. Induction of autoimmune myocarditis increased the expression of myosin-class II MHC in the heart and enhanced their APC functions. This result is a direct demonstration that epitopes of a self-antigen involved in initiating an autoimmune disease are endogenously processed and presented within the target organ.

Animals↗

Outcome of urgent percutaneous transluminal coronary angioplasty in acute myocardial infarction: comparison of single-vessel versus multivessel coronary artery disease.

Despite recent clinical trials of percutaneous transluminal coronary angioplasty (PTCA) in acute myocardial infarction, specific groups of patients that may benefit from adjunctive or alternative therapy have yet to be adequately characterized. The in-hospital outcome of 151 consecutive patients treated for acute myocardial infarction with urgent PTCA of the infarct-related artery was studied to identify a subgroup of patients at high risk. Patients were divided into two groups based on the angiographic presence of either single-vessel (n = 86) or multivessel (n = 65) coronary artery disease. Despite PTCA of only the infarct-related artery and similar baseline clinical characteristics such as age, peak serum creatine kinase concentration, left ventricular ejection fraction, and time from the onset of chest pain to arrival at the hospital, the group with multivessel disease had a lower rate of successful angioplasty (75% vs 92%, p < 0.005), with higher incidences of persistent total occlusion of the infarct-related artery (14% vs 3%, p < 0.02) and procedural complications during PTCA (28% vs 13%, p < or = 0.02), and were more likely to have multiple complications (12% vs 1%, p < 0.004). In addition, the group with multivessel disease had a higher rate of urgent (< or = 24 hours) coronary artery bypass graft surgery (13% vs 2%, p < 0.05) and a trend toward a higher in-hospital mortality rate (6% vs 1%, p < or = 0.17). By stepwise logistic regression, only the presence of single-vessel versus multivessel disease was predictive of PTCA success (p < 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Evidence against melanin as the mediator of retinal phototoxicity by short-wavelength light.

Albino and pigmented (black-hooded) rats of the Sprague-Dawley and Long Evans strains, respectively, were compared in terms of their susceptibility to retinal damage by ultraviolet-A light. Anesthetized animals were exposed to ultraviolet-A light (lambda max = 360 nm) for 4 hr and retinal damage was assessed 1 week later by electroretinographic analysis and measurement of outer nuclear layer thickness. Albino and pigmented animals showed approximately the same severity of ultraviolet-A retinal damage as a function of exposure irradiance. Furthermore, both pigmentation strains showed swelling and vesiculation of rod inner segment mitochondria as an early manifestation of damage. An abbreviated study on a congenic rat strain (F344-c/+) of albino and pigmented littermates again demonstrated an equal susceptibility to ultraviolet-A phototoxicity for both pigmentation phenotypes. These findings provide evidence that melanin is not the mediator of short-wavelength phototoxicity to the retina, since damage readily occurred in albino animals completely lacking this chromophore.

Albinism, Ocular↗

Adverse reactions of low osmolality contrast media during cardiac angiography: a prospective randomized multicenter study.

A multicenter study was performed to determine the incidence of adverse reactions to two contrast media with similar low osmolality during cardiac angiography. The study was of a randomized double-blind design comparing ioxaglate (an ionic dimer) and iopamidol (a nonionic compound) and included 500 patients; 250 patients received ioxaglate and 250 iopamidol. There were 58 adverse reactions attributed to the contrast media in the ioxaglate group and 29 in the iopamidol group (p less than 0.001). Chest pain occurred in 11 patients in the ioxaglate group compared with 5 in the iopamidol group (p = 0.123). Nausea or vomiting was present in 20 and 2 patients, respectively (p less than 0.0003). Allergic adverse reactions, such as bronchospasm, urticaria and itching, occurred in 15 of the ioxaglate group and only 1 of the patients receiving iopamidol (p less than 0.0007). Fifty-two patients in the ioxaglate group had a known allergic history (not to contrast medium) or asthma, whereas 77 receiving iopamidol had a similar history. Seven of the 52 ioxaglate-treated patients developed an allergic adverse reaction compared with none of the 77 in the iopamidol group (p = 0.001). Of 41 patients receiving ioxaglate who were premedicated with diphenhydramine, 4 had an allergic adverse event. In the iopamidol group 45 patients received similar premedication and none had an allergic adverse reaction (p less than 0.03). Thus, this multicenter study shows that adverse reactions occur more often with ioxaglate than with iopamidol and that patients with an allergic history have a greater risk with ioxaglate therapy compared with iopamidol.

Adult↗

Neutralization of endogenous tumor necrosis factor ameliorates the severity of myosin-induced myocarditis.

Tumor necrosis factor (TNF) and interferon gamma (IFN-gamma) are pluripotent cytokines and have multiple functions during the inflammatory response. Using a murine model of autoimmune myocarditis, we studied the role of TNF and IFN-gamma in myocardial inflammation. Neutralizing monoclonal antibodies against TNF-alpha/beta and IFN-gamma were administered to myosin-immunized A/J mice to assess the effect on the severity of myocardial inflammation. Anti-TNF treatment significantly reduced the severity of myocarditis compared with rat immunoglobulin G or saline controls (p less than 0.0007) when given before myosin immunization. Myosin-specific lymph node T-cell proliferation studies showed no difference in the proliferative response between the anti-TNF-treated mice and controls. Administration of anti-TNF to mice after myosin immunization had no effect on the severity of inflammation. This suggests that TNF is an important mediator early in the pathogenesis of myocardial inflammation in this model of myocarditis. Neutralization of IFN-gamma significantly increased the severity of myocarditis compared with rat immunoglobulin G and saline controls (p less than 0.0065), suggesting that IFN-gamma may function as an important regulatory cytokine early in the pathogenesis of myocardial inflammation. Understanding the functions of cytokines during the inflammatory response to myocardial injury may provide important information on possible methods to limit myocardial damage.

Animals↗

Morphologic comparisons between rhodopsin-mediated and short-wavelength classes of retinal light damage.

The histologic manifestations of rhodopsin-mediated versus short-wavelength classes of retinal phototoxicity were compared after spectral exposures of the albino rat retina. Animals were exposed to wave-bands of light centered at the peak of rhodopsin absorbance (green, 500 nm) or in the ultraviolet A (UVA; 360 nm). Intensity-damage curves generated for each wave-band indicated that UVA light was 50-80 times more effective than green light at causing photoreceptor cell losses. Examination of early ultrastructural changes in rod inner segments, outer segments, and retinal pigment epithelium revealed a remarkable degree of similarity between UVA and green light-induced damage. Furthermore, the two classes of damage were indistinguishable in terms of post-exposure recovery from threshold damage and regional distribution of photoreceptor cell loss along the vertical meridian. The finding of essentially identical histologic manifestations for the two classes of damage raises the possibility that they share a common biochemical etiology or pathway of cell destruction.

Animals↗

Diabetic retinopathy.

The risk of blindness is 25 times greater in diabetics than nondiabetics. Medical, laser, and surgical interventions have the potential to enhance greatly the prognosis of maintaining useful vision throughout life. Patient education is paramount to improve comprehension of the condition, recommended treatment modalities, and compliance with prescribed regimens. Nursing assessments and interventions related to anxiety, discomfort, ineffective coping mechanisms, and immobility add a quality link in the multidisciplinary approach surrounding the delivery of care to patients with diabetic retinopathies.

Adult↗

Effects of collaborative education on patient satisfaction and knowledge.

This study details an experimental study that utilized a collaborative educational approach for teaching 50% of a group of patients diagnosed with Diabetic Macular Edema and who underwent Focal Argon Laser treatment. The control group received teaching only by their physician. The registered nurses cared for the control patients, providing comfort interventions and maintaining a safe environment, but did not participate directly in the teaching program.

Aged↗

Influence of operating parameters on reproducibility in capillary electrophoresis.

The reproducibility of two migration parameters (retention time and mobility) of a seven-component test mixture was examined under various operating conditions using laboratory-built capillary electrophoresis systems. It was found that the frequency of rinsing the capillary and the solutions used for rinsing had the greatest effect on migration reproducibility. In addition, it was found that the migration behavior of solutes that interact with micelles is not repeatable unless the proper rinse protocol is applied. Inconsistent migration behavior is linked to inconsistent total current of the system. Preliminary investigations indicate that the fluctuation in total current were associated with non-equilibrium conditions between the buffer and the capillary wall.

Electrophoresis↗

Myosin-induced acute myocarditis is a T cell-mediated disease.

The heart is a target organ in several autoimmune diseases, and therefore it is important to understand more about the effector cells involved in immune-mediated mechanisms of myocardial cell death. Because immune T lymphocytes are central to many immune responses, we wanted to study the role of T cells in causing cardiac specific inflammation. We used purified mouse cardiac myosin to cause acute myocarditis in mice. The adoptive transfer of purified T cells from C.B-17 mice with active myocarditis to SCID recipients successfully transferred the disease into SCID hosts. In contrast, transfer of serum with high-titer antimyosin antibodies to SCID hosts did not cause myocarditis. Using mAb to deplete A/J mice of CD4+ T cells, we showed that these mice were protected against the induction of myocarditis. Depletion of CD8+ T cells reduced the severity of inflammation but did not prevent induction of myocarditis. We were also able to prevent the induction of myocarditis using major histocompatibility class II protein-binding, nonimmunogenic, competitor peptides. These blocking studies also indicated that in H-2k mice, myocarditis is an I-Ak-restricted disease, and provided further evidence that CD4+ T cells are critical to the induction of disease. Together, these studies provide direct evidence that myosin-induced myocarditis is a T cell-mediated disease.

Acute Disease↗

Micellar electrokinetic capillary chromatography of acidic solutes: migration behavior and optimization strategies.

Micellar electrokinetic capillary chromatography (MECC) is suitable for the separation of mixtures of uncharged and charged solutes. In this paper, the migration behavior of acidic compounds in MECC is quantitatively described in terms of different models. These equations describe the relationships between the two migration parameters in MECC (retention factor and mobility) and the two important experimental parameters (pH and micelle concentration) that have a great influence on the migration behavior and selectivity. Interestingly, the mobility and retention factor of a given solute could behave differently with the variations in pH. This would raise a question of which parameter actually represents the migration behavior of a solute in MECC: retention factor (a chromatographic parameter) or mobility (an electrophoretic parameter). The consequences of micellar-mediated shifts of ionization constants on selectivity and optimization strategies in MECC are discussed. The mathematical models would allow the prediction of migration behavior of solutes based on a limited number of initial experiments. This would greatly facilitate the method development and optimization of separations of ionizable compounds by MECC and, in addition, important physical and chemical characteristics of solutes such as their apparent ionization constants in micellar media and their partition coefficients into micelles (over a wide range pH values) can be determined. The models were verified, as good agreements were observed between the predicted and the experimentally observed migration behavior. Based on the preliminary results, the pH and micelle concentration are likely to be interactive parameters in many situations. As a result, simultaneous optimization of these two parameters would be the most effective strategy to enhance the MECC separation of acidic solutes.

Chromatography↗

The recognition of self-antigens and autoimmune disease.

Recent studies have increased our understanding of the nature of autoimmune recognition and of the identity of autoantigens, at least in model systems. Knowledge of the autoantigens and the process of recognition is suggesting new therapies for autoimmune disease.

Animals↗

Application and evaluation of enzyme-linked immunosorbent assay and immunoblotting for detection of antibodies to Treponema hyodysenteriae in swine.

An enzyme-linked immunoassay (ELISA) has been developed to detect serum Immunoglobulin antibodies G and M to Treponema hyodysenteriae in vaccinated, experimentally infected and naturally infected swine. Naturally infected swine gave ELISA titres that were similar to experimentally infected swine, but were significantly less than the titres of vaccinated swine. When serum from naturally infected swine was used to probe nitrocellulose blots of sodium dodecyl sulphate-polyacrylamide gel electrophoresed whole cell proteins of T. hyodysenteriae, the immunoblotting patterns showed IgG antibodies were produced against many T. hyodysenteriae protein antigens and against lipopolysaccharide (LPS). The IgG antibodies directed against LPS were serotype-specific for that LPS and could be used to identify the serotype involved in the T. hyodysenteriae infection in that herd. IgM immunoblots also reacted with the many protein antigens but were less specific for LPS antigen, with a substantial degree of cross-reaction between the LPS of all serotypes. The data demonstrate that a microplate enzyme-linked immunosorbent assay, coupled with immunoblotting, is a very specific and sensitive test for detection of antibody to Treponema hyodysenteriae in swine.

Animals↗