Prototype glucose-oxygen sensor for the artificial pancreas.
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Alkenes↗
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A total delivery system of genetically engineered drugs or cells for diseased vessels. Concept, materials, and fabricated prototype device.
The development of a percutaneous procedure using a catheterized system for diseased vessels has been increasingly in demand in conjunction with gene therapy using genetically engineered drugs (antisense) and cells. The authors' strategic concept realizes revascularization at narrowed, diseased sites and delivery of drugs or cells into the diseased tissues or targeted cells. An inflatable, drug-releasing double balloon is installed at the tip of a catheter. The outer balloon, fabricated with micropores (diameters of 20 and 30 mm) by an excimer laser ablation technique, releases a viscous solution containing a photoreactive polymer and drug or cells on inflation of the inner balloon. A photoresponsive water-soluble polymer, molecularly designed for its ability to achieve prolonged local residency of antisense DNA at the tissue level and enhanced transmembrane transport at the cellular level, is premixed with antisense oligonucleotide drug. On light irradiation, the nonionic polymer is reversibly converted to a positively charged polymer that can be complexed with highly negatively charged antisense DNA (c-myb), which may enhance the transmembrane delivery of antisense. On cessation of irradiation, the complex slowly dissociates to function intracellularly as an antisense drug, resulting in inhibition of cell proliferation. Thus, our integrated, dual-function balloon system may contribute to mechanical dilatation gene therapies at diseased vessels.
Angioplasty, Balloon, Coronary↗
An oxygenator with a built-in hemoconcentrator. In vitro performance and pre clinical in vivo assessment of the final prototype.
To facilitate the handling of cardiopulmonary bypass (CPB) and simplify the circuit, the authors have developed a new membrane oxygenator with a hemofiltration function. The hollow fiber units for gas exchange and hemofiltration were combined in concentric circles in a cylindrical housing. The total priming volume was 190 ml. Because the authors adopted a silicon coated hollow fiber membrane for gas exchange, this oxygenator was completely resistant to serum leakage, even after treatment to make the device hydrophilic. Both units possess a blood-outside perfusion system. Filtered fluid was collected easily through a stopcock mechanism. The oxygen transfer rate was 312 ml/min at a blood flow rate of 6 L/min, and the ultrafiltration rate was 3.5 L/hr at a blood flow rate of 4 L/min with a 25% hematocrit and 200 mmHg transmembrane pressure in an in vitro study. The pressure drop was 62 mmHg at a blood flow rate of 4 L/min. The authors found no adverse effects in an in vivo study using a mongrel dog. In conclusion, this durable, combined device could achieve excellent and simplified hemoconcentration through having all the blood in the unit flow through the hemofiltration portion, and was useful not only in cardiopulmonary bypass during open heart surgery, but also in extracorporeal membrane oxygenation.
Animals↗
Small intrapulmonary artery lung prototypes. Mathematical modeling of gas transfer.
Two diffusion models have been developed to analyze gas transfer data previously measured in an intravascular artificial lung consisting of a central gas supply catheter from which are tethered a large number of blind-ended microporous fibers of equal length. A convective-diffusion model (CD) describes the countercurrent transfer of a binary gas pair when gas is supplied at constant pressure conditions, and a well mixed (WM) cycled pressure model predicts transfer when the gas supply pressure is time cycled between compression and vacuum conditions. Regression of gas to gas and liquid to gas excretion data with the CD model resulted in estimates of the liquid phase mass transfer coefficient kAI. Because these values were intermediate between the kAI expected for flow parallel to a cylinder and for flow normal to a cylinder, gas transfer was influenced by both the tethered region of the fiber that was nearly perpendicular to the axis of the test section and the free end of the fiber that rested along the wall of the test section. With a time cycled gas supply pressure, the enhanced carbon dioxide and oxygen excretion predicted by the WM model was similar to the data, but a loss in transfer efficiency with fiber length was not accounted for by the theory.
Algorithms↗
A hybrid mock circulatory system: testing a prototype under physiologic and pathological conditions.
Hydraulic models of circulation are used to test mechanical heart assist devices and for research and training purposes. However, when compared with numerical models, they are rather expensive and often not sufficiently flexible or accurate. Flexibility and accuracy can be improved by merging numerical models with physical models, thus obtaining a hybrid model where numerical and physical sections are connected by an electrohydraulic interface. This concept is applied here to represent left ventricular function. The resulting hybrid model is inserted into the existing closed loop model of circulation. The hybrid model reproduces ventricular function by a variable elastance numerical model. Its interaction with the hydraulic sections is governed by measuring left atrial and systemic arterial pressures and computing the left ventricular output flow by the resolution of the corresponding equations. This signal is used to control a flow generator reproduced by a gear pump driven by a DC motor. Results obtained under different circulatory conditions demonstrate the behavior of the ventricular model on the pressure-volume plane and report the trend of the main hemodynamic variables.
Heart↗
Functional properties of a prototype rheolytic catheter for percutaneous thrombectomy. In vitro investigations.
RATIONALE AND OBJECTIVES: The performance of a rheolytic catheter designed to provide rapid fragmentation and evacuation of debris was evaluated. Specifically, fragmentation and evacuation efficiency was investigated in vitro. METHODS: Fragmentation, aspiration, and recanalization of large thrombotic occlusions (8-cm length, 6-mm inner diameter) composed of clot (n = 11) or collagen gels (n = 20) of different stiffness were performed with different jet pressures at rates optimized by visual observation and were recorded on videotape for subsequent analysis. The size and number of the resulting particles in the evacuated fluid and those remaining in the artificial vessel were determined using filtration and laser light scattering techniques. The rate of fragmentation, mean particulate size, and efficiency of evacuation were evaluated as a function of operating parameters and "clot stiffness." RESULTS: Complete fragmentation of fresh thrombus occurred at 11,000 psi by direct action of the 6 radially disposed jets, which created a trapping vortex from which most of the particles (80%) were evacuated by suction. At lower pressure (5,500 psi), fragmentation efficiency was unchanged for fresh thrombus and softer 5% gels. Ninety-five percent of the thrombus was fragmented in very small particles with a mean diameter of 0.8 +/- 0.4 micron, while 5% of the mass of the fragmented thrombus was in particles > 40 microns. At 11,000 psi, the maximal rate of advancement associated with complete material fragmentation decreased with stiffness. For very stiff gels or heavily cross-linked old thrombus, complete fragmentation and removal of material was not achieved. CONCLUSION: The high-pressure rheolytic catheter rapidly fragmented and evacuated large thrombi much larger than the catheter diameter--features with potential for treating large thrombi, such as acute pulmonary emboli or deep vein thrombi. However, this rapid forceful disruption may damage vessel walls and invariably creates a broad range of particulate sizes, which makes evacuation of almost all of the particulate material imperative to minimize clinically relevant distal embolization.
Catheterization↗
Ytterbium- and dysprosium-EOB-DTPA. A new prototype of liver-specific contrast agents for computed tomography.
RATIONALE AND OBJECTIVES: A series of studies was conducted to determine whether metal complexes of the EOB-DTPA type are useful as contrast agents for computed tomography (CT). METHODS: Metal complexes using EOB-DTPA as ligand were synthesized with lanthanide metal ions (lanthanum [La], cerium [Ce], praseodyme [Pr], gadolinium [Gd], dysprosium [Dy], ytterbium [Yb], and lutetium [Lu]) and with nonlanthanides (lead [Pb] and bismuth [Bi]). Complex stability was assessed by measuring binding to bone meal. The physicochemical parameters partition coefficient, osmolality, viscosity, and protein binding were determined in vitro. Tolerability was tested both in vitro (thromboplastin time, effect on erythrocytes) and in vivo (acute, neural, and cardiovascular toxicities). Biliary excretion and tissue distribution, especially liver, kidney, and bone concentrations, were measured in rats after intravenous doses of 0.5 mmol/kg. Imaging performance using CT was investigated in vitro in a phantom model and, for Gd-EOB-DTPA, in vivo by injecting doses of 0.5 mmol/kg into healthy or tumor-bearing rats and rabbits. RESULTS: The kinetic stability of M-EOB-DTPA complexes differed widely. Nonlanthanide metals, especially Pb-EOB-DTPA, provided less stable complexes than lanthanides with an optimum of stability for the metals Gd, Dy, Yb, and Lu. Tolerability was good for all compounds, best results were obtained for Gd and Yb. Concentrations in rat liver after administration of Gd-EOB-DTPA, 0.5 mmol/kg intravenous, were approximately 1 mumol/g, resulting in CT enhancement of 16 Hounsfield units (HU). Tumor tissue was not enhanced. In rabbits, at the same dose level 30 HU was found. CONCLUSIONS: Metal complexes of the EOB-DTPA type, especially those of Gd and Yb seem to be useful as iodine-free liver-specific contrast agents for CT.
Animals↗
Rehabilitation: the prototype for holistic health policy formation.
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Persons with Disabilities↗
Comparison of the Nebraska collar, a new prototype cervical immobilization collar, with three standard models.
OBJECTIVES: To determine whether a novel immobilization collar called the Nebraska collar would restrict motion of the cervical spine better than three traditional designs: the Philadelphia collar, the sterno occipital mandibular immobilizer (S.O.M.I.), and the Lehrman-Minerva cervical orthosis. DESIGN: Cervical spine radiographs and a compass were used to assess motion allowed by four separate cervical collars placed on volunteers. SETTING: University-affiliated level one trauma center. PATIENTS/PARTICIPANTS: Fourteen paid volunteers (six females and eight males) between the ages of twenty and thirty-five years (mean twenty-five years) were recruited. MAIN OUTCOME MEASUREMENTS: The maximum amount of flexion, extension, and lateral bending permitted by each collar was assessed by cervical radiographs taken of the volunteers while wearing each of the four collars. Maximum rotation was measured with a compass positioned on the top of the head of the volunteers and oriented in the horizontal plane. RESULTS: The Nebraska collar restricted rotation (p < 0.0001) and lateral bending (p < 0.0001) significantly more than did the other three orthoses. In total maximum extension from occiput to C7, the Nebraska collar was found to be more restrictive than the Philadelphia collar (p < 0.05) and the S.O.M.I. (p < 0.05). In total maximum flexion, there was no statistically significant difference among the four collars. When the total maximum flexion-to-extension motion was measured, both the Nebraska and Lehrman-Minerva cervical collars were found to be more restrictive than the Philadelphia collar (p < 0.05). CONCLUSION: The new Nebraska collar provides stabilization that is significantly more rigid than the other models tested, with no difference in patient comfort.
Adult↗
Vascular selectivity of seven prototype calcium antagonists: a study at the single cell level.
Vascular selective calcium antagonists (CAs) show an improved tolerance and a reduced incidence of adverse cardiac effects, especially in treatment of hypertension. The effects of seven well-known CAs on contractions of single isolated rat myocytes were studied and compared with their effects on stimulated 45Ca2+ uptake of rat aortic smooth muscle cells (A7r5 cell line). In the latter test system, the order of potency to inhibit 45Ca2+ uptake was as follows (pIC25, -logM): isradipine (9.2), felodipine (8.7), nifedipine (8.5), nisoldipine (8.5), nicardipine (8.1), verapamil (6.7), and diltiazem (6.5). The potencies for inhibition of ventricular myocyte contraction at 0.5 Hz were (pIC25): isradipine (6.9), nisoldipine (6.7), felodipine (6.6), nicardipine (6.5), nifedipine (6.5), verapamil (5.3), and diltiazem (4.8). Thus, the order of vascular selectivity (i.e., the ratios of IC25 cardiocytes/IC25 A7r5 cells) was: isradipine (184), felodipine (128), nifedipine (107), nisoldipine (63), diltiazem (48), nicardipine (43), and verapamil (23). When ventricular cells were stimulated at 1 Hz, the order of selectivity was changed: Diltiazem was the least selective. Verapamil, diltiazem, and felodipine showed a highly frequency-dependent negative inotropic effect, whereas the effects of the other dihydropyridines were less affected by the frequency of stimulation. CAs show different degrees of vascular selectivity and different frequency-dependent profiles, and vascular selectivities are also dependent on experimental conditions. Selectivity is thus not necessarily related to chemical classes of drugs (e.g., dihydropyridines) or to different binding sites at the channel protein but could instead be due to varying dissociation rates from the respective binding sites at the channel in its different voltage-dependent states.
Animals↗
Controlling unwanted sources of threshold change in disability glare studies: a prototype apparatus and procedure.
One of the main purposes of cataract surgery is to reduce the debilitating effects of light scatter by the lens. An important effect of this intraocular forward scatter is to produce a veiling retinal illuminance from a glare source. The retinal contrast of the stimulus is thus reduced, and a quantifiable "disability glare" effect may be measured. A complication is introduced by the fact that intraocular scatter arises from other sources in addition to the lens. All present tests of glare disability fail to eliminate or control for these factors, nor do they control for the light adaptation effect of the glare source. The effects of lens removal may not be predicted accurately by such tests, and patients may report little improvement in visual function after surgery. The goal of this research is to provide the background for developing a method of measuring disability glare due only to light scatter in the lens. Thirty-seven patients with mild to moderate cortical cataracts served as subjects. A disability glare effect (DG) was measured with a Maxwellian-view system that eliminates or controls scatter from the iris, sclera, and retina, and which controls for light-adaptation effects from the glare source. DG with this method showed a significant correlation with objective measures of lens light back scatter. Suggestions were made for improvements in the apparatus and procedures for future clinical studies.
Aged↗
A postgraduate course in orthopaedic nursing: one prototype.
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Curriculum↗
Selective incorporation of the prototype melanoma seeker thiourea into nascent melanin: a chemical insight.
The mechanism of selective incorporation of thiourea into melanotic melanoma was investigated by model experiments in which the effect of the compound was examined at various stages of melanogenesis in vitro. Up to 50% inhibition of dopachrome formation was observed in the tyrosinase-dopa reaction in the presence of thiourea at a 2:1 molar ratio with respect to the substrate. Under these conditions, a major product was formed which was isolated and identified as a 1:1 dopa-thiourea adduct (adduct I). Subsequent stages of the oxidation were characterized by the development of a yellow chromophore (lambdamax 440-460nm), virtually identical to that obtained by separate oxidation of the adduct I. A less remarkable effect of thiourea was observed on the oxidative polymerization of 5,6-dihydroxyindole (DHI) and 5,6-dihydroxyindole-2-carboxylic acid (DHICA) which was apparent on spectrophotometric and high pressure liquid chromatography (HPLC) analysis. Radiolabelling experiments with 14C-thiourea showed that the label was initially incorporated into the adduct I, while in the subsequent stages of the oxidation it was associated with pigmented materials which escaped direct analysis. Incorporation of labelled thiourea into dopa-melanins was found to be significantly higher than incorporation into synthetic pigments from indole precursors. These results provide a chemical basis for the interpretation of the selective accumulation of thiourea in those melanoma areas with high rates of melanin synthesis seen in autoradiographic experiments.
Antineoplastic Agents↗
The acute phase response and exercise: the ultramarathon as prototype exercise.
OBJECTIVE: Controversy exists in relation to the nature of the acute phase response, which is known to occur following endurance exercise. This study was conducted to demonstrate the similarities between this response and the response consequent to general medical and surgical conditions. DESIGN: This is a case series field study of serum levels of acute phase reactants in a group of ultramarathon runners competing in a 6-day track race. PARTICIPANTS: Seven male and one female experienced ultramarathon runners. INTERVENTION: A track race of 6 days duration. MAIN OUTCOME MEASURES: Serum iron, ferritin, transferrin, albumin, haptoglobin, alpha-1 antitrypsin, complement components 3 and 4, C-reactive protein, and erythrocyte sedimentation rate, total iron binding capacity, and transferrin saturation. RESULTS: Of the 11 acute phase reactants measured, 6 (serum iron, ferritin, percent transferrin saturation, C-reactive protein, erythrocyte sedimentation rate, and haptoglobin) responded as if an acute phase response was present; 5 (tranferrin, albumin, alpha-1 antitrypsin, and complement components 3 and 4) did not respond in such a fashion. CONCLUSION: This study provides further evidence that the acute phase response consequent to exercise is analogous to that which occurs in general medical and surgical conditions. The previous demonstration of the presence of the appropriate cytokines following exercise, the findings of others in relation to acute phase reactants not the subjects of this study, the possibility that a training effect leading to attenuation of the response and the realization that the acute phase response is not identical across a range of medical conditions lends weight to the above conclusion.
Acute-Phase Proteins↗
Biomonitoring of workers exposed to carcinogens: immunoassays to benzo(a)pyrene-DNA adducts as a prototype.
A new tool for the study of occupational carcinogenesis is "molecular dosimetry" or biomonitoring to establish the biologically effective dose of carcinogens in workers. Human monitoring of biologically effective dose and preclinical response has the potential to flag the need for protective measures and/or surveillance. Comparable biologically effective dose and preclinical response data in humans and laboratory animals for whom tumor incidence is known can also enhance risk extrapolation between species. This paper will provide a brief overview of biomonitoring methods now under development, including advantages, limitations, applications to date, and research needs. Application to the monitoring of worker populations requires careful thought about the use to which monitoring data will be put.
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗
The HIV epidemic in the Amazon Basin is driven by prototypic and recombinant HIV-1 subtypes B and F.
This paper describes genetic subtypes of HIV-1 found in blood samples from 31 HIV-1-infected people who visited the Counseling and Testing AIDS Center of Instituto de Medicina Tropical in Manaus, Brazil. Manaus, the main city in Brazil's Amazon Basin, is also the closest urban connection for more than 100,000 Indians living in the rain forests of this region. Although to date there is no evidence of increased incidence of HIV-1 infection among the indigenous population, our understanding of both the prevalence and nature of the epidemic in the region as a whole is limited. From the 31 samples analyzed by C2V3 sequencing, we found almost equal proportions of HIV-1 strains belonging to subtype B (n = 16; 51.6%) and subtype F (n = 15; 48.4%), a finding that differs from results from previous studies conducted in urban areas of southeastern Brazil. We also observed the presence of the GWGR amino-acid sequence in the critical tetra-peptide crown of the env V3 loop in the HIV-1 subtype B samples analyzed. Among these samples, we also found 14 mosaic genomes (45.16%) in which different combinations of subtypes B, C, and F were identified between the p24 gag, pro, and env regions. Our data support the hypothesis that the Amazonian HIV-1 infections linked to the urban epidemic in southeastern Brazil. The genetic diversity and the prevalence of mosaic genomes among the isolates in our study confirm an integral role of recombination in the complex Brazilian epidemic.
Adult↗
Panel of prototypical infectious molecular HIV-1 clones containing multiple nucleoside reverse transcriptase inhibitor resistance mutations.
We have created a panel of recombinant HIV-1 infectious clones containing common patterns of reverse transcriptase (RT) mutations responsible for resistance to each of the currently available nucleoside reverse transcriptase inhibitors (NRTI), and we have submitted the panel to the National Institutes of Health AIDS Research and Reference Reagent Programme. Testing the activity of new antiretroviral compounds against this panel of drug-resistant clones will determine their relative activity against many clinically relevant NRTI-resistant viruses.
Clone Cells↗
A prototype for an economical vertical microstomia orthosis.
One of the complications of thermal injury is the development of scars and contractures during the healing process. This scarring can be devastating, especially when it involves the mouth. The purpose of this report is to describe the construction of an alternative vertical mouth stretching orthosis for vertical microstomia. By using thermoplastic splinting material and a long thread screw, a vertical mouth-stretching orthosis can be custom-fit to any patient's mouth. The device can be fabricated for a pediatric or adult patient for the rehabilitation of a circumferential mouth burn, especially targeting the vertical diameter. When using this device, patients gave positive feedback for comfort and ease of use, with increased mouth mobility and range of motion. This vertical orthotic device provides an economical and comfortable alternative for vertical mouth diameter enlargement to the current five devices available in the literature.
Burns↗