Biomedical subjects

K Stokes

Publications and source records attributed to K Stokes.

At least 37 records · Page 2Linked to original sources

PubMed1993

Human plasma alpha 2-macroglobulin promotes in vitro oxidative stress cracking of Pellethane 2363-80A: in vivo and in vitro correlations.

It is hypothesized in this study that the phenomenon of environmental stress cracking (ESC) in polyetherurethane is caused by a synergistic action of biological components in the body fluids, oxidative agents, and stress. An in vitro system is designed to mimic the in vivo system; human plasma contains certain biological components that can act as a stress cracking promoter, while H2O2 (Co) solution provides an oxidative reaction comparable to that observed in the respiratory burst of adherent macrophages and foreign-body giant cells. It is demonstrated that the phenomenon of in vivo stress cracking in Pellethane 2363-80A is duplicated by an in vitro system that involves a pretreatment of prestressed specimens with human plasma at 37 degrees C for 7 days followed by oxidation in 10% hydrogen peroxide with 0.10M cobalt chloride at 50 degrees C for 10 days. The pretreatment with plasma has a synergistic effect with the oxidation by H2O2 (Co) treatment to produce ESC. A plasma component responsible for promoting stress cracking in Pellethane polyurethane is identified to be alpha 2-macroglobulin (alpha 2M).

Animals↗

PubMed1992

Phase I clinical and pharmacokinetics study of high-dose toremifene in postmenopausal patients with advanced breast cancer.

Toremifene is an antiestrogen that binds strongly to estrogen receptors (ER). A total of 19 previously treated postmenopausal women with metastatic breast cancer whose performance status was good and whose ER status was positive or unknown were studied to determine the maximum tolerated dose of toremifene. Cohorts of patients received 200, 300, or 400 mg/m2 p.o. daily until relapse or unacceptable toxicity had occurred. Nausea, vomiting, and dizziness were dose-related. Three of five patients receiving 400 mg/m2 experienced moderate or severe vomiting and another developed reversible disorientation and hallucinations. Mild sweating, peripheral edema, vaginal discharge, and hot flushes were encountered at all doses. Reversible corneal pigmentation was identified in seven cases but was not of clinical importance. The pharmacokinetics of toremifene was studied weekly and in detail on day 42 using a high-performance liquid chromatographic (HPLC) assay that identified the parent compound and three active metabolites, N-desmethyltoremifene, (deaminohydroxy)toremifene, and didemethyltoremifene. Steady state was achieved at 1-3 weeks. The toremifene area under the curve and the maximal concentration were dose-dependent at high doses. The recommended phase II dose is 300 mg/m2 p.o. daily.

Adult↗

PubMed1991

[Early and late results of percutaneous transluminal angioplasty (PTA) in diabetic patients].

Results of 127 iliac and femoropopliteal transluminal angioplasties in 97 diabetic patients are presented. Patients who had undergone iliac (n = 70), femoral (n = 41), and popliteal (n = 16) angioplasties for stenoses up to 15 cm long were followed up for 6-60 months. In diabetic patients presenting with only claudication or adequate runoff, the 5-year iliac patency rate was 76% and the femoral patency rate was 60%; these results were comparable with those found in non-diabetic patients. For limb salvage, 3-year patency rates were 66% for iliac, 37% for femoral, and 37% for popliteal angioplasties, and 5-year patency rates were 29% for iliac, 7% for femoral, and 0% for popliteal angioplasties. Our findings suggest that the overall decreased PTA success rates typically associated with diabetes are due to the larger percentage of these patients who present with symptoms of severe peripheral vascular disease and not to the presence of diabetes per se.

Adult↗

PubMed1990

Cellular interactions with biomaterials: in vivo cracking of pre-stressed Pellethane 2363-80A.

The phenomenon of stress cracking of Pellethane 2363-80A (PEU) was investigated using the cage implant system. A cytotoxic polyvinylchloride (PVC) and a silicone rubber containing an anti-inflammatory steroid were used to create inflammatory environments in which the biostability of the pre-stressed PEU was tested. These coimplants provided alternative in vivo environments to study in vivo polymer interactions. The inflammatory responses to the implanted cages were monitored by analyzing the exudates aspirated from the cages at different implantation times over 21 days. The pre-stressed PEU specimens were retrieved after 5, 10, and 15 weeks postimplantation and examined by optical microscopy (OM) and scanning electron microscopy (SEM). The results support the conclusion that in vivo cracking of stressed (strained) Pellethane 80A is related to cell-polymer interactions. Severe cracking or rupture of the implanted PEU specimens was observed as early as 5 weeks postimplantation. Molecular chain degradation of the implanted specimens was evident from molecular weight measurements. Neither surface cracking nor degradation of macromolecules was found on the pre-stressed PEU specimens with the added cytotoxic PVC implanted over 15 weeks. No cracking was observed on the pre-stressed specimens in the presence of steroid silicone rubber, even after 10 weeks implantation.

Animals↗

PubMed1990

A new efficient NanoTip lead.

The ideal lead has low, stable acute and chronic thresholds, high pacing impedance, and good sensing. Leads with low, stable thresholds have been developed, but pacing impedance has been in the 600 omega region. One way to increase pacing impedance is to decrease the electrode's surface area. The threshold performance and sensing ability of less than 5 mm2 electrodes have been considered questionable, up to now. We have developed a 1.5 mm2 porous, platinized, steroid-eluting electrode and have demonstrated in canine studies that it has excellent performance. Chronic thresholds are low at about 0.65 +/- 0.28 V (ventricular) and 0.42 +/- 0.12 V (atrial) at 0.5 msec. Chronic pacing impedance is in the 1200-1300 omega region, but mean chronic R and P wave source impedance is less than or equal to 1500 omega. Sensing is excellent, with almost double the P wave amplitudes usually measured in the canine.

Animals↗

PubMed1990

The in vivo auto-oxidation of polyether polyurethane by metal ions.

The first large scale use of polyether polyurethane elastomers in long term human implants was as insulation for cardiac and neurologic pacing leads. While the performance of these polymers has generally been very good over a 14-year period, several failure mechanisms have been discovered that involve interactions between the devices, materials and the body. One of these is auto-oxidation of soft segment ether through the intermediate action of certain transition metal ions, derived from conductor wires by corrosion processes. Biologically produced oxidants appear to be an accelerating factor. In this study, Pellethane 2363-80A tubing containing conductor coils or mandrels of various metals or controls were implanted in rabbits. Explants were analyzed as a function of implant time by optical and scanning electron microscopy, electron dispersive analysis by X-ray, stress-strain, FTIR, GPC and AA spectrophotometry. Only cobalt produced bulk oxidative degradation while surface damage was found in the presence of cobalt bearing alloys. No evidence of significant auto-oxidation was found in the presence of silver, nickel, chromium, molybdenum, iron, titanium, platinum, 304 stainless steel, glass or empty tubing. The combination of polyether polyurethane and metals (especially those containing cobalt) in an implantable device must be carefully evaluated for biostability prior to human use.

Biocompatible Materials↗

PubMed1989

Sequence specificity of pausing by DNA polymerases.

We have constructed recombinant M13 DNA templates containing stretches of oligo (purines) and oligo (pyrimidines). Each of these inserts hinders the advancement of the large fragment of E. coli Pol I during DNA synthesis. The pattern of blockage is independent of changes in KCl or Mg2+ concentrations and pausing is moderately alleviated at lower pH. Blockage is not affected by either the concentration of template or by the position of the DNA primer. The pattern of pause sites is similar for calf thymus DNA polymerase-alpha, implying that replicative barriers are determined by the structure of the DNA at its growing point. There is a lack of correlation between the position of pause sites with different inserts and known alternate DNA structures. Thus, the homo-oligomeric inserts may possess a different structure when complexed with DNA polymerase. This concept accounts for the appearance of unique new upstream and downstream pause sites that result from the insertion of each oligonucleotide.

Base Sequence↗

PubMed1988

The porous titanium steroid eluting electrode: a double blind study assessing the stimulation threshold effects of steroid.

A transvenous pacing lead with a porous electrode which slowly elutes the steroid, dexamethasone sodium phosphate, has been developed. Previous investigations show low and constant stimulation thresholds persisting over at least the first two years post-implantation. As it is not known whether this low threshold results from the steroid or electrode configuration, a double blind study was designed to compare the same electrode configuration with and without steroid over a 2-year follow-up period. There were ten patients in each group with similar age, sex, indications for pacing and implantation data. Regular measurements of postoperative pulse duration thresholds were performed using a customized VVIM pulse generator programmed to 1.5 V output. For the first two days post-implantation, there were no statistical differences in the pulse duration thresholds between the two pacing leads. From 2 weeks to 2 years the pulse duration thresholds for the steroid leads remained almost constant, whereas the leads without steroid showed a typical rise. The difference in pulse duration thresholds between the two groups of leads from two weeks onwards confirmed that it was the steroid rather than the electrode configuration which prevented the rise in chronic stimulation threshold.

Aged↗

PubMed1987

Promotion of diabetes onset by stress in the BB rat.

The purpose of the present study was to address the question of whether environmental stress affects the age of onset and incidence of overt insulin-dependent diabetes mellitus in an animal model of human Type 1 (insulin-dependent) diabetes. Thirty-five diabetes prone BB rats of both sexes were divided into two groups: experimental animals were exposed to multiple, concurrent, and unpredictable environmental stressors, while littermate controls were exposed to a standard lab environment. Groups were housed in two separate, sound attenuated, independently ventilated, and restricted rooms. By age 150 days, experimental group animals had developed overt diabetes at a significantly earlier age.

Animals↗

PubMed1987

Limitations of indirect methods of estimating small bowel transit in man.

Experiments were carried out in healthy volunteers to explore the utility of a new [14C]lactulose breath test for measuring small intestinal transit time in man and to use this procedure to test whether two antidiarrheal agents, codeine and clonidine, alter small intestinal transit time during digestion of a liquid meal. In an initial validation study performed in 12 subjects (three studies in each subject), a liquid test meal containing 10 g [14C]lactulose was administered and the colonic entry time estimated from the time course of 14CO2 excretion in breath compared with that of H2 excretion. There was a fair correlation (r = 0.77; P less than 0.001) between results obtained by the two methods; both methods gave similar results, but 14CO2 output was delayed when compared to H2 output and was incomplete. The meal also contained xylose and [13C]glycine, permitting the duodenal entry time of the meal to be estimated by the appearance of xylose in blood and 13CO2 in breath, respectively. The same liquid meal was then used to examine the effect on small intestinal transit time (colonic entry time minus duodenal entry time) of codeine or clonidine. 99Tc-sulphur colloid was also added to the meal to permit a comparison of small intestinal transit estimated by imaging with that estimated by the 14CO2-lactulose breath test. 99Tc radioactivity appeared in the cecum (as assessed using gamma scintigraphy) about 2 hr before 14CO2 radioactivity appeared in breath; the correlation between transit time estimated by the two methods was moderate (r = 0.61; P less than 0.05). Based on the [14C]lactulose data, small intestinal transit time ranged from less than 1 to 3 hr for a liquid meal containing 10 g lactulose; within-subject variation (coefficient of variation 17%) was considerably less than between-subject variation (coefficient of variation 56%). Codeine increased the small intestinal transit time significantly (from 2.7 +/- 0.3 hr to 5.0 +/- 0.9 hr; mean +/- SE), whereas clonidine did not alter small intestinal transit time, as estimated by the colonic entry time minus duodenal entry time. Neither drug influenced duodenal entry time. These results suggest that the [14C]lactulose breath test, which has only moderate accuracy, may have occasional utility as a convenient, noninvasive method for estimating small intestinal transit time in man. However, this study also suggests that indirect methods of estimating small bowel transit in man have limitations, variability, and possibly may lack the desired sensitivity.

Antidiarrheals↗

PubMed1987

Autooxidative degradation of implanted polyether polyurethane devices.

While certain polyether polyurethanes have been shown to be biostable, undesirable interactions between polymer, the body environment and device can occur. For example, the corrosion products of metallic parts can cause relatively rapid autooxidation of polyether soft segments. This phenomenon was first demonstrated in our laboratories by immersing polyurethane test specimens in metal ion solutions of different oxidation potentials. Subsequently, the mechanism was reasonably duplicated by immersing Pellethane 2363-80A insulated cardiac pacing leads in 3%, 37 degrees C hydrogen peroxide. In vivo studies after 1 year show that corrosion products from pure Co and Fe produce the most rapid degradation of the polyurethane.

Animals↗

PubMed1985

Identification of a tumor cell-derived differentiation antigen on mouse colony-forming units in the spleen and progenitor cells.

Surface membrane antigen(s) expressed on a mouse mast cell line (FMP1) have also been shown to occur on hemopoietic spleen colony-forming units (CFU-S) and granulocyte/macrophage colony- and erythroid burst-forming cells, using a xeno-antiserum raised against FMP1 cells. This mast cell model has been used to obtain antiserum and large quantities of antigen for the biochemical identification of CFU-S and progenitor cell antigen(s). Immunoprecipitation of FMP1 membrane antigens with the antiserum and subsequent polyacrylamide gel electrophoresis revealed the presence of five membrane proteins with molecular weights of 28,000, 32,000, 36,000, 50,000, and 70,000. Mouse B-lymphoma cell line W279 which reacted with anti-FMP1 serum was found to possess three immunoprecipitable surface proteins with molecular weights of 32,000, 50,000, and 70,000. Attempts have been made to identify the antigen(s) expressed by CFU-S and progenitors which were revealed by immunoprecipitation from the tumor lines. The three lower-molecular-weight proteins (Mr 28,000-36,000) were chosen for initial study. Membrane extracts of FMP1 cells were fractionated on Sephacryl S-200, and selective pools of these antigens were made. Antisera to these pools exhibited complement-dependent cytotoxicity to FMP1 cells, bone marrow CFU-S, granulocyte/macrophage colony-forming cells, and erythroid burst-forming units. These antisera immunoprecipitated Mr 28,000, 32,000, and 36,000 proteins from FMP1 cell membrane extracts but not the Mr 50,000 and 70,000 antigens. The W279 line has only one antigen (Mr 32,000) in the lower-molecular-weight range and is able to absorb anti-CFU-S and anti-progenitor activity, which suggests that it is this antigen which is expressed on hemopoietic cells. In addition, thymocytes react with anti-FMP1 serum, and the Mr 32,000 antigen was immunoprecipitated from thymus cell extracts. Binding studies with concanavalin A, wheat germ agglutinin, and lentil lectin indicated that the Mr 28,000-36,000 proteins were glycoproteins. The apparent molecular weights of these proteins on polyacrylamide gels were not altered by reduction and alkylation and therefore do not contain disulfide-linked subunits.

Animals↗

PubMed1984

Wallbar clamp.

Explore the source record for details and available documents.

Exercise Therapy↗

PubMed1983

Sexual orientation and sex role conformity.

Homosexuals are stereotypically viewed as deviating from the conventional sex role standards of our society. Homosexual males are regarded as effeminate, while homosexual females are seen as masculine. Some limited empirical support for these stereotypes has been reported in the literature. However, results remain inconclusive. In order to provide a further test of these stereotypes, 186 male and female homosexual, bisexual, and heterosexual subjects were administered the Bem Sex Role Inventory. Results showed no significant support for prevailing stereotypes. Possible reasons for the discrepancy between these findings and previous reports are explored and suggestions are offered for future research.

Adult↗

PubMed1983

Experimental and clinical study of a new permanent myocardial atrial sutureless pacing lead.

A new permanent lead has been developed for atrial epicardial use. Early clinical evaluation (26 human implants) following thorough canine studies indicates that the new lead is safe, effective, and reliable. Canine thresholds and P-wave amplitudes as a function of implant time are similar to those of transvenous atrial "J" leads. Human thresholds at implant are higher than canine, but change less with time. Implant and acute repositioning were found to be easy. There have been no lead-related operations.

Animals↗

PubMed1983

A combined atrial/ventricular lead for permanent dual-chamber cardiac pacing applications.

A new urethane insulated dual unipolar atrial/ventricular transvenous lead has been developed to facilitate implantation of permanent dual-chamber cardiac pacing systems in man. The atrial portion of the lead has tines and is designed to retain a permanent J configuration, while the coaxially situated ventricular lead is freely and independently adjustable and incorporates a ring tip electrode with four urethane tines. Our initial experience with the dual lead in one patient is reported herein and suggests that combined atrial/ventricular pacing leads are feasible and may obviate need for implantation of two separate pacing electrodes in patients being considered for permanent dual-chamber pacing.

Electrodes, Implanted↗

PubMed1983

Implant experience with unipolar polyurethane pacing leads.

A total of 905 unipolar polyurethane pacing leads have been implanted by the first author's group, between April 1978 and February 1982, with a mean implant of 1.4 years. Twelve leads were explanted and analyzed. Eleven of the explanted leads exhibited some degree of surface damage or "frosting." Of the 11, five atrial (Medtronic 6991 U) and one ventricular (Medtronic 6971) lead suffered complete insulation failure. One lead was completely free from surface damage. Clinically, insulation failure presented as muscle stimulation and/or battery depletion. Surface damage appears to be due to an environmental stress cracking (ESC) mechanism. ESC requires both a surface active agent from the hostile biological environment, and stress in excess of a threshold value. The minor surface damage or "frosting" of the eleven explanted leads was typically 10 to 15 microns deep on leads implanted about one year, although one device (15 months) had 30 micron cracks. No lead failures in this series were attributed to this shallow cracking mechanism. The severe cracking of the six Medtronic leads leading to insulin failure was thought to be due to the unusually high tensile stresses imposed by manufacturing processes and ligatures. The incidence of failure was 7% (5/74) for the Medtronic 6991 U and 0.2% (1/454) for the Medtronic 6971. Medtronic lead manufacturing processes have been modified to reduce the high residual tensile stresses and a fixation sleeve has been added to reduce ligature stress.

Arrhythmias, Cardiac↗

PubMed1982

Polyether polyurethanes for implantable pacemaker leads.

Two variations of a commercially available polyether polyurethane were evaluated for certain physical properties and the changes in those properties as a result of plasticization by absorbed moisture. Appropriate tests were done to establish biocompatibility. A two-year rat implant study evaluated chronic biocompatibility and biostability. Ten tumours were found in 34 animals, of which eight were considered unrelated to the materials. Two fibrosarcomas were presumed to be the result of solid-state carcinogenesis, not related to the material per se. Material testing included analysis of density, tensile strength, elongation, molecular weight, intrinsic viscosity, scanning electron microscopy, differential scanning calorimetry, and infrared spectrum changes. The polyether polyurethane was considered to be biocompatible and biostable for long-term implant.

Animals↗