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Biomedical subjects

K D Kramer

Publications and source records attributed to K D Kramer.

14 recordsLinked to original sources

Organ mapping using parelectric spectroscopy.

Whenever physical methods are used in the field of diagnostics, it is necessary to find an unambiguous mapping of the properties of the tested tissues (e.g. normal or pathologic) to their answer to the respective analysis tool such as nuclear magnetic resonance (NMR), ultrasound, x-rays or the relatively new method of parelectric spectroscopy (PS). The well-established non-invasive NMR method has, by now, a sufficiently wide-spread atlas of such mappings. This has to be contrasted to the situation of the PS method where first experiments showed the fulfillment of conditions necessary for any reliable diagnosis, namely the uncertainties of the results being small compared to the differences between the normal and pathologic state of the tissues under test. To help close this gap, we present here results of the behaviour of 12 different organs of mice, taken 20 min after excision and give the dependence of the two most essential PS parameters, the dipole density Delta epsilon and the mobility f(0), on the type of healthy organs. To be able to use tumorous tissues preserved in formaldehyde after excision for comparison purposes, we have been measuring the changes of some organs between the fresh state and the preserved state under formaldehyde for over 180 min each.

Animals↗

Lipid nanoparticles for skin penetration enhancement-correlation to drug localization within the particle matrix as determined by fluorescence and parelectric spectroscopy.

With topical treatment of skin diseases, the requirement of a high and reproducible drug uptake often still is not met. Moreover, drug targeting to specific skin strata may improve the use of agents which are prone to cause local unwanted effects. Recent investigations have indicated that improved uptake and skin targeting may become feasible by means of nanoparticular systems such as solid lipid nanoparticles (SLN), nanostructured lipid carriers (NLC) and nanoemulsions (NE). Here we describe techniques to characterize drug loading to carrier systems and skin penetration profiles by using the lipophilic dye nile red as a model agent. Since the mode of drug association with the particle matrix may strongly influence the efficiency of skin targeting, parelectric spectroscopy (PS) was used to differentiate between matrix incorporation and attachment to the particle surface and fluorescence spectroscopy (FS) to solve dye distribution within NLC particles. Nile red was incorporated into the lipid matrix or the covering tensed shell, respectively, of SLN and NLC with all the lipids studied (Compritol, Precirol, oleic acid, Miglyol). In NLC, the dye was enriched in the liquid phase. Next, nile red concentrations were followed by image analysis of vertical sections of pigskin treated with dye-loaded nanoparticular dispersions and an oil-in-water cream for 4 and 8 h in vitro. Following the SLN dispersions, dye penetration increased about fourfold over the uptake obtained following the cream. NLC turned out less potent (<threefold increase) and penetration appeared even reduced when applying a NE. In contrast to previous studies with glucocorticoids attached to the surface of SLN, a targeting effect was not detected here. Therefore, drug targeting appears to be more strictly related to the mode of interaction of drug and particle than penetration enhancement.

Administration, Topical↗

Parelectric spectroscopy of drug-carrier-systems--distribution of carrier masses or activation energies.

The answer of a high-frequency electromagnetic wave to a sample as termination of an open-ended coaxial line gives the mobility and the density of permanent electric dipole moments in the substance under test. As long as these dipoles are attached to carrier molecules of well defined masses, both parameters can be extracted from the reflected wave in a quick manner giving unambiguous results. The corresponding algorithm has been applied to solid lipid nanoparticles with glucocorticoid molecules attached to or incorporated in the carrier molecules. The results from measurements in the frequency region (0.1-100) MHz have recently been published. As soon as we have to envisage a distribution in carrier masses and/or in activation energies of the attached molecules, we have to apply a more sophisticated evaluation algorithm. The need for a more generalised algorithm is clear as well, when we have to deal with more than one dipole-carrying constituent in the samples. All these evaluation algorithms shall be presented together with the mathematical basis in a short but exact form.

Drug Carriers↗

Glucocorticoid entrapment into lipid carriers--characterisation by parelectric spectroscopy and influence on dermal uptake.

Topical glucocorticoids such as betamethasone 17-valerate (BMV) and prednicarbate (PC) are an important therapeutic option in atopic eczema. To reduce the risk of dermal atrophy, we aimed at BMV incorporation into solid lipid nanoparticles (SLN) for epidermal targeting using various lipids and emulsifiers corresponding to previous work on PC. Cutaneous absorption into excised human skin was compared to the one with a cream. While Compritol-based particles increased BMV uptake about fourfold we failed, however, to obtain epidermal targeting. To obtain insight into the location of active substance relative to the carrier, we used the recently optimised method of parelectric spectroscopy (PS). In fact, we were able to study electric dipole movements in the broad field of a frequency span from 0.1 to 100 MHz demonstrating that glucocorticoids are attached to the particle surface but are not incorporated into the lipid matrix. With BMV, the loading capacity of the particle surface lies clearly below the usual concentration of 0.1% which is not the case with PC. An adequate association of drug and carrier is essential for epidermal targeting. Parelectric spectroscopy provides insight into the interaction between drug and lipidic carrier.

Adult↗

[Parelectric spectroscopy for noninvasive diagnosis of laryngeal tissue].

Under the influence of an external electrical field, every biological tissue displays characteristic parelectric properties that can be recorded by radiofrequency spectroscopy in a noninvasive contact mode. Parelectric spectroscopy was investigated for its utility as a complementary noninvasive diagnostic procedure in examinations of the larynx, in particular in terms of its ability to differentiate tissue properties. Parelectric spectroscopy was performed in 10 patients submitted to surgical ablation of vocal cord neoplasia under local or insufflation anaesthesia. Measurements were obtained in the area of the neoplasia, and in macroscopically normal tissue in the corresponding vocal cord. In all cases, intra-individual comparison with normal vocal cord tissue revealed lower dipole density and reduced mobility of the affected vocal cord. In addition, the difference between normal and pathological tissue in terms of the parelectric parameters increased with age. The absolute values of dipolar density and mobility revealed no tendency to correlate with different kinds of vocal cord neoplasia. Parelectric spectroscopy may be a useful additional diagnostic tool for monitoring the course of epithelial changes in the larynx.

Adolescent↗

Depression, disease severity, and sickle cell disease.

The present study examined depressive symptomatology in 440 adults with sickle cell disease (SCD). Participants completed the Center for Epidemiologic Studies--Depression scale (CES-D) as part of their yearly routine visits to the Duke University--University of North Carolina Comprehensive Sickle Cell Center. They also completed questions regarding demographics, disease severity, pain, and health care use. Data analyses revealed that the percentage of patients with SCD exhibiting significant depressive symptomatology dropped from 43 to 18% when a more stringent cutoff was used on the CES-D, suggesting that future studies should determine the most valid cutoff score for identifying depression in patients with SCD. Gender and family income were positively and significantly associated with depressive symptomatology. Also, patients who reported more frequent painful episodes were more likely to report depressive symptoms. Implications for assessment and treatment of depression in adults with SCD are discussed.

Adult↗

[Dielectric spectroscopy for noninvasive examination of corneal tissue].

Dielectric spectroscopy is a non-invasive contact technique that permits the in vivo measurement of the specific electrical properties of biological tissue induced by an external electrical field. Permittivity, relaxation time and specific conductivity as a function of corneal hydration (wet weight/dry weight) and temperature were measured in 10 porcine corneas. Variation of tissue hydration has a minor influence on the signal, with a significant variation of the signal being detectable only for relatively dry tissue. A much greater influence was found for temperature, in particular on relaxation times. Dielectric spectroscopy provides us with an opportunity to detect structural, in particular temperature-induced, changes in living tissue. In the frequency range investigated, hydration has only a small influence on the dielectric properties of the tissue.

Animals↗

Dielectric spectroscopy as a sensor of membrane headgroup mobility and hydration.

Dielectric spectroscopy is based on the response of the permanent dipoles to a driving electric field. The phospholipid membrane systems of dimyristoylphosphatidylcholine and dioleoylphosphatidylcholine can be prepared as samples of multilamellar liposomes with a well known amount of interlamellar water. For optimal resolution in dielectric spectroscopy one has to design the experimental set-up so that the direction of the permanent headgroup dipole moment is mostly parallel to the field vector of the external radio frequency (rf) electric field in this layered system. A newly developed coaxial probe technique makes it possible to sweep the measuring frequency between 1 and 1000 MHz in the temperature range 286-323 K. The response yields both the dispersion (epsilon') and the absorption part (epsilon") of the complex dielectric permittivity, which are attributed to the rotational diffusions of the zwitterionic phosphatidylcholine headgroup and the hydration water, respectively. Although the contributions of the headgroup and the hydration dipole moments to the dielectric relaxation are found to be situated close together, we succeeded in separating them. In the language of the Debye description, we propose to assign the lower frequency portion of the signal response to the relaxation contributed by the headgroups. The respective relaxation frequency is a discrete value in the range of 15-100 MHz and it shows normal temperature dependence. The contribution of the hydration water molecules exhibits a similar behavior in the range of 100-500 MHz but with the attributed relaxation frequency as the center of an asymmetric distribution of frequencies in analogy to simulation models known from the literature. Activation energies are derived for each of these relaxation processes from the Arrhenius plots of the temperature-dependent relaxation frequencies.

Dimyristoylphosphatidylcholine↗

The sickle cell mutual assistance movement.

The purpose of this paper is to describe the mutual help movement that is occurring in the sickle cell community. As sickle cell disease primarily affects African Americans in the United States, the research can show how mutual assistance groups are proliferating among this group of individuals. The study will provide the only qualitative analysis of mutual assistance groups known to exist that are primarily comprised of African Americans. In addition, demographic information on the leaders of these groups will be reported. This information can serve to educate individuals interested in forming mutual assistance groups for individuals affected by sickle cell disease. It is hoped that this information will broaden the perspective of mutual assistance groups and will illustrate that mutual assistance groups also serve diverse cultures in this country.

Black or African American↗

Sickle cell mutual assistance groups and the health services delivery system.

One of the main reasons individuals with sickle cell disease (SCD) join self-help groups is to address the problems they perceive in the health care delivery system, such as long delays in hospital emergency departments, inadequate training of health care workers about SCD, and frequent accusations of drug-seeking behavior. This formative evaluation study surveyed the leaders of 11 self-help groups which are attempting to make changes in the health care system, representing 8% of the 134 known SCD self-help groups. The group leaders reported the problems their groups perceived in health care delivery, the obstacles they encountered in trying to make changes in the system, and the approaches they employed in addressing the perceived problems. This study shows that, in educating themselves and others about the experience of SCD, the members of the groups have taken a pro-active role in their own health care which gives them a sense of empowerment that they would not otherwise have. The activism of the SCD self-help groups is also helping to redefine the traditional relationship between patient and provider, and it signals an emerging new role for self-help groups in general.

Anemia, Sickle Cell↗

Influence of electromagnetic fields on the enzyme activity of rheumatoid synovial fluid cells in vitro.

Since positive clinical effects have been observed in the treatment of rheumatoid arthritis with electromagnetic fields of weak strength and low frequency range (magnetic field strength: 70 microT; frequency: 1.36-14.44 Hz), an attempt was made to analyse the effects of these electromagnetic fields on enzyme activity in monolayer cultures of rheumatoid synovial fluid cells after single irradiation of the cultures for 24 hours. We only investigated the matrix metalloproteinases (collagenase, gelatinase, proteinase 24.11 and aminopeptidases). It was found that electromagnetic fields of such a weak strength and low frequency range do not generally have a uniform effect on the activity of the different proteinases in vitro. While aminopeptidases do not show any great changes in activity, the peptidases hydrolysing N(2,4)-dinitrophenyl-peptide exhibit a distinct increase in activity in the late phase in culture medium without fetal calf serum. In the presence of fetal calf serum this effect is not observed and enzyme activity is diminished. Our experiments do not show whether such a phase-bound increase in the activity of proteinases in vitro is only one finding in a much broader range of effects of electromagnetic fields, or whether it is a specific effect of weak pulsed magnetic fields of 285 +/- 33 nT on enzyme activity after single irradiation. This question requires further elucidation.

Amino Acid Sequence↗

Inhibition by manoalide of fMLP-stimulated elastase release from human neutrophils.

Incubation of human polymorphonuclear leukocytes (PMNLs) with the chemotactic factor N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLP) resulted in a concentration-dependent release of the neutral protease elastase. This response was inhibited by pretreatment of the PMNLs with manoalide (IC50 approximately 0.08 microM). To understand the mechanism of this inhibition, we examined the effect of manoalide on the signal-transduction pathway believed to mediate fMLP stimulation. We observed in fura-2 loaded cells that pretreatment with manoalide blocked fMLP-induced increases in cytosolic free-calcium (IC50 approximately 0.15 microM). However, manoalide had no effect on inositol 1,4,5-trisphosphate (IP3) production at concentrations which completely inhibited the Ca2+ signal. Furthermore, manoalide was approximately 50-fold less potent as an inhibitor of phospholipase C activity in membrane preparations of PMNLs than as an inhibitor of calcium mobilization in whole cells. These data indicate that manoalide can block stimulation of human PMNLs through inhibition of Ca2+ mobilization, but that this occurs at a site beyond phospholipase C activation and inositol phosphate turnover.

Anti-Inflammatory Agents, Non-Steroidal↗

Modifying food purchases in supermarkets with modeling, feedback, and goal-setting procedures.

We compared several procedures designed to modify consumer food purchases with the objectives of reducing fat and increasing carbohydrate content, and reducing dollar expenditures on food. Participants were 126 volunteer community households which, after a 7-week baseline period, were randomly assigned to video-modeling, video-modeling-feedback, video-lecture, video-lecture-feedback, participant-modeling, video-modeling-discussion, and control conditions. The main dependent measure was a weekly record of food purchases, convertible to percentages of nutrients and dollar expenditures. Results indicated that modeling-feedback and participant-modeling procedures were most effective (e.g., 6% reduction of total fat consumption, 19% dollar savings). Strategies to refine and automate modeling and feedback in supermarkets that may benefit consumers, corporations, and government are discussed.

Journal Article↗