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Whole blood immunoadsorption of anti-A or anti-B antibodies.

Immunoadsorption columns capable of specifically removing antibodies show promise as an alternative treatment to plasma exchange. Most columns are designed to be perfused with plasma and it is necessary to use a plasma separation device (filtration or centrifugation) for the procedure. This increases the cost and complexity of the immunoadsorption procedure. We have adapted immunoadsorption columns capable of removing anti-A or anti-B red cell antibody from plasma to a whole blood perfusion system by coating the silica with a thin layer of collodion and incubating with albumin (1%). Patients were given heparin, 25 units/kg intravenously, followed by a continuous infusion of 3% citrate and heparin, 10 units/ml, to achieve a ratio of 1:16-1:20 (anticoagulant to whole blood) before delivery through the columns. Effective and specific removal of anti-A or anti-B antibody was achieved with this technique. Effects on coagulation parameters and the complement system were acceptably small.

ABO Blood-Group System↗

A comparison of heat exchangers for blood cardioplegia.

During open heart surgery, myocardial protection provided by oxygenated blood-based cardioplegia is superior to that provided by non-oxygenated crystalloid cardioplegia. However, the widespread use of blood cardioplegia has been limited by the cost and complexity of the associated cooling and delivery systems. The performance of a simple system--a polyethylene coil immersed in ice--has been compared with three systems incorporating specialized, water-jacketed heat exchangers: Buckberg Shiley, Shiley BCD and Bentley HE-100. Blood was diluted to a haematocrit of 22% and delivered to each cooling system at flow rates of 200-500 mL/min and temperatures of 25 degrees C and 30 degrees C. Cooling water at 0-1 degree C was supplied to the heat exchangers at flow rates of 2, 4, and 6 L/min. Performance was measured by comparing the blood outflow temperatures at the same inflow temperature under a variety of test conditions which simulated those occurring in clinical practice. All cooling systems, except the Buckberg Shiley, were able consistently to cool blood cardioplegia adequately (below 10 degrees C), but the ice coil was the most effective. The heat exchanger systems are 3-4 times more expensive than the ice coil and require an external source of cold water. Thus the ice coil system has the advantages of simplicity, efficiency, and economy.

Heart Arrest, Induced↗

Effect of zidovudine treatment in late pregnancy on HIV-1 in utero transmission.

In Thailand, the prevalence of paediatric HIV-1 infection has increased rapidly through vertical transmission. According to the ACTG 076 trial regimen, zidovudine treatment in HIV-infected pregnancy can reduce vertical transmission. However, this treatment is complex and costly. It is not applicable for developing countries. We conducted a study to evaluate the effect of zidovudine treatment in late pregnancy on HIV-1 in utero transmission. Fifty cases of asymptomatic HIV-1 infected-women were voluntarily enrolled to the study. Zidovudine 250 mg orally twice a day was given to these patients from gestational age 36 weeks until labour. The newborns were evaluated at birth by a neonatologist and peripheral blood was tested for HIV genome by PCR technique within 48 hours of birth. The study revealed that no HIV genome was detected from the peripheral blood of newborns. It is suggested that zidovudine treatment in late pregnancy could reduce HIV-1 in utero transmission.

AIDS Serodiagnosis↗

LDL hemoperfusion--a new procedure for LDL apheresis: first clinical application of an LDL adsorber compatible with human whole blood.

To date, lipid apheresis procedures can remove low-density lipoprotein (LDL) cholesterol (LDL-C) only from plasma. Thus, initially plasma has to be separated from the blood cells, which increases the costs and complexity of the extracorporeal circuit. This paper describes the first clinical application of a new LDL adsorber that eliminates LDL directly from whole blood. The goal of this pilot study was to test the efficacy, safety, and feasibility of direct lipoprotein adsorption in patients. In a 2 center Phase II clinical trial, 12 hypercholesterolemic patients suffering from overt coronary or peripheral artery disease were treated once with LDL hemoperfusion. The new LDL adsorber (DALI, Fresenius, St. Wendel, Germany) contained 480 ml of polyacrylate coated polyacrylamide gel. The anticoagulation consisted of an initial heparin bolus followed by an acid citrate dextrose (ACD)-A infusion during the treatment. The processing of nearly 1 patient blood volume resulted in a reduction of LDL-C by 45 +/- 8% and triglycerides by 23 +/- 20%. HDL-C, fibrinogen, and cell counts were not significantly influenced. In a subgroup of 5 patients who exhibited elevated lipoprotein (a) (Lp[a]) levels, Lp(a) reduction was 43 +/- 15% (all results corrected for plasma volume shifts). The sessions were clinically uneventful; the system was technically safe and easily handled. In conclusion, short-term LDL hemoperfusion by the DALI proved to be a safe, effective, and simple procedure for the treatment of patients suffering from symptomatic recalcitrant hypercholesterolemia. The present study represents a solid basis for the clinical long-term evaluation of this new technique in the future.

Acrylic Resins↗

Caring for the new uninsured: Hospital charity care for older people without coverage.

Despite near-universal coverage through Medicare, a number of elderly residents in the United States do not have health insurance coverage. To the author's knowledge, this study is the first to document trends in the use of hospital charity care by uninsured older people. Data from the New Jersey Charity Care Program, which subsidizes hospitals for services provided to low-income uninsured people, were used to analyze trends in charity care utilization by older people from 1999 to 2004. Charity care charges are standardized to uniform Medicaid reimbursement rates and inflation adjusted using the Medical Care Consumer Price Index. From 1999 to 2004, use of charity care by older people grew much faster than it did for younger patients. As a result, older people now account for a greater share of hospital charity care in New Jersey than children. Elderly users of charity care generated higher costs per patient than their younger counterparts. Cost differences were especially salient at the upper end of the distribution, where high-cost elderly patients used significantly more resources than high-cost patients in other age groups. These results highlight an emerging source of strain on the healthcare safety net and point to a growing population of uninsured residents who have costly and complex medical needs. Similar experiences are likely to be found in other states, especially those that have growing populations of elderly immigrants who are likely to lack health insurance.

Adult↗

Use of DNA microarray technology and gene expression profiles to investigate the pathogenesis, cell biology, antifungal susceptibility and diagnosis of Candida albicans.

The use of DNA microarrays is becoming the method of choice for assaying gene expression, particularly as costs and complexity are being reduced as the technology becomes more widespread and better standardized. A DNA array is nothing but a collection of probes fixed on a solid support. The probes can be PCR products of ORFs or short intragenic oligonucleotides deposited or synthesized in situ by photolithographic methods. To date, sequencing projects for fungal genomes have yielded 10 complete genomes and 21 whole shotgun sequences, including Candida albicans strain SC5314. Sequencing of the C. albicans genome has led to the construction of whole-genome DNA microarrays for in vitro transcription profiling by several universities and companies. The use of microarray or DNA chip techniques for Candida research has started recently but the number of studies using this technology is increasing rapidly, in order to address important remaining questions about pathogenesis, cell biology, antifungal susceptibility, and diagnosis.

Antifungal Agents↗

A comparison of partial and full mouth scoring of plaque and gingivitis in oral hygiene studies.

The clinical testing necessary to demonstrate the safety and efficacy of new toothbrushes is complex and expensive. Any modification of methodology that could reduce complexity and cost without compromising quality would benefit both investigators and the public. Results from an 8-week toothbrush study were assessed for the use of partial as compared to full-mouth evaluations. The potential utility of an objective, minimally-invasive bleeding index for the evaluation of gingivitis was also tested. 2 partial evaluations, half-mouth and molar/anteriors, revealed decrements in modified gingival index (MGI), bleeding index and plaque index that were statistically significant and similar in magnitude to those derived from full-mouth examinations. % decrements in MGI and bleeding index based on the Ramfjord teeth were not significant statistically. Results for the new sulcular bleeding index were essentially similar to those for the MGI. However, the bleeding index offered the advantage of improved objectivity for use in both white and non-white subjects. These results suggest that partial evaluations and the new bleeding index may be useful elements in the design of toothbrush efficacy studies.

Adult↗

DNA microarray technology for neonatal screening.

Modern molecular biology, owing much to the Human Genome Initiative, has elucidated many of the genetic mechanisms underlying heritable metabolic disease. While the use of molecular methods has flourished in research laboratories, complexity and cost have limited their utility in newborn screening. Newborn blood cards provide high quality DNA samples able to provide reliable support to highly multiplexed polymerase chain reactions (PCR). New manufacturing processes have reduced the cost of DNA microarray technology to the point where it is a practical tool for population screening. In a single assay, a DNA microarray facilitates the co-detection of amplification products diagnostic for several genetic diseases. High throughput is achieved with automation at every step, from DNA extraction to detection of hybrids. We suggest that it is both feasible and practical to develop a first-tier newborn screening protocol based upon multiplex PCR and analysis of amplification products using DNA microarrays. Initial data utilizing the model systems of sickle cell disease, alpha-1-antitrypsin deficiency and Factor V Leiden will be reported.

DNA↗

Chronic hepatitis C infection in a rural Medicaid HMO.

CONTEXT: Chronic hepatitis C infection (CHCI) is an increasingly common problem, affecting about 2% of the US population. The cost and complexity of treatment and difficulties in communicating with the infected population are of concern to insurers and health planners. PURPOSE: To describe the clinical features of patients with CHCI in a rural Medicaid-covered population and to describe a method developed for treating CHCI in an underserved rural community. METHODS: We developed a disease management approach to patients with CHCI receiving insurance coverage through a Medicaid HMO in rural Oregon. A locally based multidisciplinary hepatitis committee was formed to develop a management protocol and a process for selecting patients for treatment. The committee met monthly to develop the treatment plan for individual patients. Day-to-day treatment was provided by a nurse under the supervision of the committee. FINDINGS: One hundred forty-three adults with CHCI were identified by their primary care physicians. About half the patients had a type 1 genotype. Treatment with pegylated interferon and ribavirin was completed on 21 persons, 11 (52%) of whom had a virologic cure. Problems with treatment toxicity were common. Patient satisfaction with the treatment by the nurse was high. CONCLUSIONS: CHCI is common in this rural, nonminority Medicaid-insured population. A locally based disease management model was developed that was well received by patients and was successful in delivering a high quality of care for people with CHCI in a rural area.

Adolescent↗

Studies of regression of advanced atherosclerosis in experimental animals and man.

In general, the results to date in humans and experimental animals seem to indicate that substantial regression of advanced atherosclerosis is possible. The results also indicate that the advanced atherosclerotic lesions are much more likely to respond favorably if the serum cholesterol concentrations are reduced to the minimum that prevails in animals or people who consume a low-fat low-cholesterol diet. In human subjects and in rhesus monkeys, this value appears to be about 150 mg%. Under these circumstances, much of the lipid disappears from the plaques, and the remaining fibrous tissue and cells appear to condense and undergo remodeling, as they do in fracture or wound healing. Additional effort will be required to ascertain how rapidly and how much of the fiber proteins and calcium can be removed from the advanced plaques and to work out methods that will consistently produce regression of advanced atherosclerotic lesions in human subjects. This goal would appear to be worth working toward. Interruption of progression of atherosclerosis appears to be more easily achieved, and it also would appear to be a worthwhile goal. The diagram that is reproduced as FIGURE 2 presents the multiple methods of intervention in atherosclerosis that are now available to the physician and to the patient. To those of us who look on atherosclerosis as an almost completely preventable disease and one that is largely reversible, the following quotation from the perceptive essay by Lewis Thomas seems to be prophetic and most appropriate. An extremely complex and costly technology for the management of coronary heart disease has evolved, involving specialized ambulances and hospital units, all kinds of electronic gadgetry and whole platoons of new professional personnel to deal with the end results of coronary thrombosis. Almost everything offered today for the treatment of heat disease is at this level of technology, with the transplatned and artificial hearts as ultimate examples. When enough has been learned for us to know what really goes wrong in heart disease, we ought to be in a position to figure out ways to prevent or reverse the process; and when this happens, the current elaborate technology will be set to one side.

Animals↗

Bayesian identification of a population compartmental model of C-peptide kinetics.

When models are used to measure or predict physiological variables and parameters in a given individual, the experiments needed are often complex and costly. A valuable solution for improving their cost effectiveness is represented by population models. A widely used population model in insulin secretion studies is the one proposed by Van Cauter et al. (Diabetes 41:368-377, 1992), which determines the parameters of the two compartment model of C-peptide kinetics in a given individual from the knowledge of his/her age, sex, body surface area, and health condition (i.e., normal, obese, diabetic). This population model was identified from the data of a large training set (more than 200 subjects) via a deterministic approach. This approach, while sound in terms of providing a point estimate of C-peptide kinetic parameters in a given individual, does not provide a measure of their precision. In this paper, by employing the same training set of Van Cauter et al., we show that the identification of the population model into a Bayesian framework (by using Markov chain Monte Carlo) allows, at the individual level, the estimation of point values of the C-peptide kinetic parameters together with their precision. A successful application of the methodology is illustrated in the estimation of C-peptide kinetic parameters of seven subjects (not belonging to the training set used for the identification of the population model) for which reference values were available thanks to an independent identification experiment.

Adult↗

Determining effective centroid position in biomechanical testing: a technique for simplifying whole bone analysis.

BACKGROUND: Whole bone in vitro biomechanical compressive testing can be complicated by three factors: sample asymmetry, heterogeneous material properties, and unknown effective centroid location. METHOD OF APPROACH: The technique presented here facilitates the calculation of effective centroid position, modulus of elasticity and equivalent uniform strain magnitude for a cross section of bone from a simple whole bone compressive test. Simplification of section response to load is achieved through a combination of linear beam and simple planer geometry theory. The technique requires three longitudinal strain gauges be affixed around the test specimen cross section of interest, gauge position need not be determined. Sample loading is then accomplished using a simple four point loading jig. RESULTS: Results of the technique are presented on an object with known elasticity and geometry, an aluminium tube, and seven pairs of equine third metacarpal whole bones. CONCLUSIONS: Average cross section modulus of elasticity, equivalent uniform cross section strain, and effective centroid locations were all predicted to within the range of published values. Employing the testing setup and analysis technique presented in this paper resulted in a significant savings in both implementation complexity and cost over previously available techniques.

Algorithms↗

A method for planar biaxial mechanical testing that includes in-plane shear.

A limitation in virtually all planar biaxial studies of soft tissues has been the inability to include the effects of in-plane shear. This is due to the inability of current mechanical testing devices to induce a state of in-plane shear, due to the added cost and complexity. In the current study, a straightforward method is presented for planar biaxial testing that induces a combined state of in-plane shear and normal strains. The method relies on rotation of the test specimen's material axes with respect to the device axes and on rotating carriages to allow the specimen to undergo in-plane shear freely. To demonstrate the method, five glutaraldehyde treated bovine pericardium specimens were prepared with their preferred fiber directions (defining the material axes) oriented at 45 deg to the device axes to induce a maximum shear state. The test protocol included a wide range of biaxial strain states, and the resulting biaxial data re-expressed in material axes coordinate system. The resulting biaxial data was then fit to the following strain energy function W: [equation: see text] where E'ij is the Green's strain tensor in the material axes coordinate system and c and Ai are constants. While W was able to fit the data very well, the constants A5 and A6 were found not to contribute significantly to the fit and were considered unnecessary to model the shear strain response. In conclusion, while not able to control the amount of shear strain independently or induce a state of pure shear, the method presented readily produces a state of simultaneous in-plane shear and normal strains. Further, the method is very general and can be applied to any anisotropic planar tissue that has identifiable material axes.

Animals↗

Use of a multiseparation fiber optic probe for the optical diagnosis of breast cancer.

We explore the effects of the illumination and collection geometry on optical spectroscopic diagnosis of breast cancer. Fluorescence and diffuse reflectance spectroscopy in the UV-visible spectral range are made with a multiseparation probe at three illumination-collection separations of 735, 980, and 1225 microm, respectively, from 13 malignant and 34 nonmalignant breast tissues. Statistical analysis is carried out on two types of data inputs: (1) the fluorescence and diffuse reflectance spectra recorded at each of the three illumination-collection separations and (2) the integrated fluorescence (at each excitation wavelength) or diffuse reflectance over the entire spectrum at all three illumination-collection separations. The results show that using the integrated fluorescence intensities recorded at a single excitation wavelength at all three illumination-collection separations can discriminate malignant from nonmalignant breast tissues with similar classification accuracy to that using spectral data measured at several excitation wavelengths with a single illumination-collection separation. These findings have significant implications with respect to the design of an optical system for breast cancer diagnosis. Examining the intensity attenuation at a single wavelength rather than spectral intensities at multiple wavelengths can significantly reduce the measurement and data processing time in a clinical setting as well as the cost and complexity of the optical system.

Breast Neoplasms↗

CT scanner selection and specification for radiation therapy.

The underlying considerations necessary for selecting a CT scanner for radiation therapy treatment planning are analyzed and discussed. To obtain best value for funds expended it is desirable to compare CT scanner mechanical characteristics, data quality, and data handling capabilities. Specifications can be written to ensure prompt delivery of a unit containing all essential features without adding to the cost or complexity of the unit.

Humans↗

Sensor array beamforming using random channel sampling: the aggregate beamformer.

The aggregate (AGG) beamformer can provide significant savings in hardware and software cost and complexity relative to conventional beamformers while retaining equivalent directional performance. The key to achieving the savings is collecting data from array channels in a random sequence, rather than simultaneously or sequentially. This allows the AGG beamformer to convert unwanted off-beam signals into wideband noise that can then be reduced by filtering. The total sampling rate is chosen to obtain the desired residual noise level and signal bandwidth. It is independent of the number of sensors. Analog anti-alias filters normally are not required, since the Nyquist frequency is determined by the total sampling rate, not the (lower) per-channel sampling rate. Beamformer delay quantization and steering resolution are greatly improved relative to conventional beamforming without the need for data interpolation. The beamformed signal, prior to decimation filtering, is obtained without arithmetic operations on the data. Low front-end hardware-complexity makes the AGG beamformer suitable for highly integrated systems. The number of sensors in the array can be altered without re-configuring buffers or altering the sampling rate. The principles of the AGG beamformer are introduced, and simulation and experimental results demonstrate performance.

Journal Article↗

Changes in multi-joint performance with age.

The purpose of this study was to determine whether elderly adults exhibit deficits in the performance of multi-joint movements. Two groups of subjects (mean ages, 68.9 and 30.1 years, respectively) participated in this experiment. Subjects performed planar arm pointing movements to various targets. One target could be achieved via elbow extension only, while the remaining 3 required both elbow extension and horizontal shoulder flexion, thus requiring coordination at the 2 joints. In contrast to the young adults, the elderly adults produced movements that became less smooth and less accurate with increasing shoulder joint contribution. The results imply a selective coordination deficit for the elderly adults. In addition, the elderly adults coactivated opposing muscles more than the young adults for the single-joint movement. However, the elderly adults reduced coactivation at both joints for the 2-joint actions, while the young adults did not. These data suggest a relationship between high coactivation levels and good performance for elderly adults. It may be more difficult for the elderly to implement high coactivation levels for multi-joint movements because of the increased energy costs and complexity of planning required in comparison to the single joint actions. Thus, to achieve motor performance, elderly persons appear to use coactivation in a manner that is fundamentally different than young adults.

Adult↗

Technology challenges in responding to biological or chemical attacks in the civilian sector.

Increasingly sophisticated technologies are needed for counterterrorism responses to biological and chemical warfare agents. Recently developed detection and identification systems are characterized by increased sensitivity, greater automation, and fewer false alarms. Attempts are also under way to reduce the cost and complexity of field-deployable systems. A broad range of decontamination reagents for equipment and personnel is emerging, but decontamination of large buildings, inaccessible spaces, and sensitive equipment remains problematic.

Automation↗