Comparing quantitative measures of erythema,pigmentation and skin response using reflectometry

We measured a number of pigmentation and skin response phenotypes in a sample of volunteers (n=397) living in State College, PA. The majority of this sample was composed of four groups based on stated ancestry: African-American, European-American, Hispanic and East Asian. Several measures of melanin concentration (L*, melanin index and adjusted melanin index) were estimated by diffuse reflectance spectroscopy and compared. The efficacy of these measures for assessing constitutive pigmentation and melanogenic dose-response was evaluated. Similarly, several measures of erythema (a*, erythema index and adjusted erythema index) were compared and evaluated in their efficacy in measuring erythema and erythemal dose-response. We show a high correspondence among all of the measures for the assessment of constitutive pigmentation and baseline erythema. However, our results demonstrate that evaluating melanogenic dose-response is highly dependent on the summary statistic used: while L* is a valid measure of constitutive pigmentation it is not an effective measure of melanogenic dose-response. Our results also confirm the use of a*, as it is shown to be highly correlated with the adjusted erythema index, a more advanced measure of erythema based on the apparent absorbance. Diffuse reflectance spectroscopy can be used to quantify the constitutive pigmentation, melanogenic dose-response at 7 d and erythemal dose-response at both 24 h and 7 d postexposure.     

Comparing Quantitative Measures of Erythema,Pigmentation and Skin Response using Reflectometry

We measured a number of pigmentation and skin response phenotypes in a sample of volunteers (n=397) living in State College, PA. The majority of this sample was composed of four groups based on stated ancestry: African‐American, European‐American, Hispanic and East Asian. Several measures of melanin concentration (L*, melanin index and adjusted melanin index) were estimated by diffuse reflectance spectroscopy and compared. The efficacy of these measures for assessing constitutive pigmentation and melanogenic dose–response was evaluated. Similarly, several measures of erythema (a*, erythema index and adjusted erythema index) were compared and evaluated in their efficacy in measuring erythema and erythemal dose–response. We show a high correspondence among all of the measures for the assessment of constitutive pigmentation and baseline erythema. However, our results demonstrate that evaluating melanogenic dose–response is highly dependent on the summary statistic used: while L* is a valid measure of constitutive pigmentation it is not an effective measure of melanogenic dose–response. Our results also confirm the use of a*, as it is shown to be highly correlated with the adjusted erythema index, a more advanced measure of erythema based on the apparent absorbance. Diffuse reflectance spectroscopy can be used to quantify the constitutive pigmentation, melanogenic dose–response at 7 d and erythemal dose–response at both 24 h and 7 d postexposure.     

Decreased levels of serum platelet-activating factor acetylhydrolase in patients with rheumatic diseases

PAF is a potent inflammatory compound known to stimulate the release of various cytokines involved in rheumatic diseases. Elevated blood PAF levels are reported in these patients. We report that serum PAF acetylhydrolase activity (AHA) levels are decreased in patients with rheumatoid arthritis or osteoarthritis as compared to healthy controls. Serum and synovial fluid AHA levels were correlated in these patients. The present study suggests the potential role of AHA in controling systemic and/or local PAF levels in patients with rheumatic diseases.     

Total radical-trapping antioxidative capacity of plasma and whole blood chemiluminescence in patients with inflammatory and autoimmune rheumatic diseases

The total radical-trapping antioxidative capacity (TRAC) of plasma was evaluated in samples from patients suffering from various inflammatory and autoimmune rheumatic diseases (n=104) and correlated with the phorbol ester-stimulated chemiluminescence (CL) of neutrophils and monocytes in unseparated blood. Plasma and blood samples from age- and sex-matched healthy volunteers (n=25) and from patients with non-rheumatic internal diseases (n=31) served as controls.

A 2 to 10 fold increase in whole blood chemiluminescence was found in rheumatic patients, which paralleled 50–80% decreased levels of plasma TRAC-values. While significant correlations between CL and TRAC were determined for patients with inflammatory arthritic diseases no correlations were found with patients suffering from connective tissue diseases. Prednisolone treatment of individual patients increased plasma TRAC-values substantially and decreased elevated levels of phagocytic CL generation to that of healthy controls.

The main potential application of the assays described here is for the convenient assessment of disease activity and progression in individual patients with rheumatic diseases.     

Physiological model using diffuse reflectance spectroscopy for nonmelanoma skin cancer diagnosis

Diffuse reflectance spectroscopy (DRS) is a noninvasive, fast, and low‐cost technology with potential to assist cancer diagnosis. The goal of this study was to test the capability of our physiological model, a computational Monte Carlo lookup table inverse model, for nonmelanoma skin cancer diagnosis. We applied this model on a clinical DRS dataset to extract scattering parameters, blood volume fraction, oxygen saturation and vessel radius. We found that the model was able to capture physiological information relevant to skin cancer. We used the extracted parameters to classify (basal cell carcinoma [BCC], squamous cell carcinoma [SCC]) vs actinic keratosis (AK) and (BCC, SCC, AK) vs normal. The area under the receiver operating characteristic curve achieved by the classifiers trained on the parameters extracted using the physiological model is comparable to that of classifiers trained on features extracted via Principal Component Analysis. Our findings suggest that DRS can reveal physiologic characteristics of skin and this physiologic model offers greater flexibility for diagnosing skin cancer than a pure statistical analysis. Physiological parameters extracted from diffuse reflectance spectra data for nonmelanoma skin cancer diagnosis.     

Lyme disease: a unique human model for an infectious etiology of rheumatic disease

Lyme disease is a complex immune-mediated multi-system disorder that is infectious in origin and inflammatory or "rheumatic" in expression. Through its epidemiologic characteristics, large numbers of a seasonally synchronized patient population are readily available for prospective study. Lyme disease has a known clinical onset ("zero time"), marked by the characteristic expanding skin lesion, erythema chronicum migrans, and a clearly defined pre-articular phase. At least some manifestations of the disorder are responsive to antibiotics, and the causative agent--a spirochete--is now known. These advantages make Lyme disease unique as a human model for an infectious etiology of rheumatic disease.     

Monte Carlo simulation of NIR diffuse reflectance in the normal and diseased human breast tissues

The spectral reflectance measurements in tissue reveal physiological meaning. Normally, functional changes like, increase in total hemoglobin concentration, decrease in oxygen saturation, etc., are observed when there is an abnormality creeping in the normal tissue. These functional changes can act together to reveal disease by non-invasive near-infrared (NIR) spectroscopy, as it influence its optical properties. In the present study, a simple two dimensional, four layer model of breast is proposed. The four layers are (i) skin (ii) adipose layer (iii) glandular tissue and (iv) muscle. Each layer is modeled with appropriate biological chromophores like hemoglobin, water, lipid and melanin. From the literature, the concentrations and molar extinction coefficients of the chromophores in various layers of the model are obtained. These values are used to calculate the wavelength dependent absorption characteristics of a particular layer. Monte Carlo simulation of diffuse reflectance (percentage of back reflected photons after multiple scattering with the broad variety of angles) are simulated for the modeled breast tissue with and without diseased condition. Near-infrared wavelengths are chosen, as the depth of penetration in tissue is more compared to UV and visible region. Simulations are carried out on the modeled breast tissue for different races (skin colors) at different NIR wavelengths. Results show significant changes in diffuse reflectance and relative absorbance for normal and diseased breast tissues for differently pigmented model. This model can be used to study the photo dynamical therapy, drug delivery and prognosis of cancer.     

Noninvasive measurement of the 308 nm LED-based UVB protection factor of sunscreens

The current method for determining the sun protection factor (SPF) requires erythema formation. Noninvasive alternatives have recently been suggested by several groups. Our group previously developed a functional sensor based on diffuse reflectance measurements with one UVB LED, which was previously evaluated on pig ear skin. Here we present the results of a systematic in vivo study using 12 sunscreens on 10 volunteers (skin types [ST] I-III). The relationship of the UVB-LED reflectance of unprotected skin and melanin index was determined for each ST. The spatial variation of the reflectance signal of different positions was analyzed and seems to be mainly influenced by sample inhomogeneity except for high-protection factors (PFs) where signal levels are close to detection noise. Despite the low-signal levels, a correlation of the measured LED-based UVB PF with SPF reference values from test institutes with R² = 0.57 is obtained, suggesting a strong relationship of SPF and LED-based UVB-PF. Measured PFs tend to be lower for increasing skin pigmentation. The sensor design seems to be suitable for investigations where a fast measurement of relative changes of PFs, such as due to inhomogeneous application, bathing and sweating, is of interest.     

Imaging hemoglobin oxygen saturation in sickle cell disease patients using noninvasive visible reflectance hyperspectral techniques: effects of nitric oxide

Sickle cell disease is characterized by microvascular occlusion and hemolytic anemia, factors that impair tissue oxygen delivery. We use visible reflectance hyperspectral imaging to quantitate skin tissue hemoglobin oxygen saturation (HbO2) and to determine whether changes in blood flow during nitric oxide (NO) stimulation or gas administration (therapies proposed for this disease) improve skin tissue oxygen saturation in five patients with sickle cell disease. Compared with six healthy African-American subjects, sickle cell patients exhibited higher forearm blood flows (7.4 +/- 1.8 vs. 3.2 +/- 0.4 ml.min-1.100 ml tissue-1, P = 0.037) but significantly reduced percentages of skin HbO2 (61.0 +/- 0.2 vs. 77.5 +/- 0.2%, P < 0.001). Administration of acetylcholine to patients increased blood flow by 15.1 +/- 3.8 ml.min-1.100 ml tissue-1 and the percentage of skin HbO2 by 4.1 +/- 0.3% (P = 0.02, P < 0.001, respectively, from baseline values). Sodium nitroprusside, a direct NO donor, increased blood flow by 3.9 +/- 1.1 ml/min and the percentage of skin HbO2 by 2.9 +/- 0.3% (P = 0.02, P < 0.001, respectively). NO inhalation had no effect on forearm blood flow, yet increased the percentage of skin HbO2 by 2.3 +/- 0.3% (P < 0.001). Percentages of skin HbO2 were exponentially related to blood flow (R = 0.97, P < 0.001), indicating a limit to skin tissue oxygen saturation at high blood flows. Thus, for acetylcholine infusion leading to blood flows sevenfold greater than those of healthy resting African-American subjects, patients still exhibited lower percentages of skin HbO2 (65.2 +/- 0.2 vs. 77.5 +/- 0.2%, P < 0.001). Visible reflectance hyperspectral imaging demonstrates that either the stimulation or the administration of NO pharmacologically or by gas inhalation improves, but does not normalize, skin tissue oxygen saturation in patients with sickle cell disease.     

Comparative study of intravital microcirculation and hemorheological changes following burn injury of different severity in rats

It was shown in experiments on rats that burn injury is followed by microcirculatory disturbances, hemoconcentration and increasing blood viscosity that is especially pronounced in the vessels with low blood pressure. The microcirculatory changes in the mesentery correlated with the in vitro investigated dynamic viscosity and blood composition. The disturbances were more pronounced after severe burn followed by a mortal shock than after moderate burn without fatal consequences. This investigation confirms great importance of hemorheological changes and microcirculatory disturbances in the early period of burn disease.     

Noninvasive determination of hemoglobin and hematocrit using a temperature-controlled localized reflectance tissue photometer

We performed visible/near-infrared optical measurements on the forearm of human subjects. We conducted four studies: one study using a commercial diffuse reflectance spectrometer, and three studies using a breadboard temperature-controlled localized reflectance tissue photometer. Calibration relationships were established between skin reflectance signal and either the reference blood hemoglobin (Hb) concentration or the hematocrit values (Hct). Prediction results were expressed as the prediction correlation coefficient (r(p)) and the standard error for cross-validation prediction (CV-SEP). Using diffuse reflectance measurement, r(p) = 0. 8, CV-SEP = 0.9 g/dL for Hb and r(p) = 0.7, CV-SEP = 3.3% for Hct (n = 40). In a localized reflectance study involving calculating the absorption and scattering coefficients and including effect of change of skin temperature in the calibration model, the best prediction results were r(p) = 0.9, CV-SEP = 0.8 g/dL for Hb and r(p) = 0.8, CV-SEP = 3% for Hct (n = 26). In a second localized reflectance study on a population having diverse skin colors at 34 degrees C, the optimal model led to r(p) = 0.8, CV-SEP = 0.9 g/dL for Hb and r(p) = 0.9, CV-SEP = 2.1% for Hct (n = 28) using the localized reflectance values without deducing the absorption and scattering coefficients. Improvement in the correlation was more noticeable for Hct than for the case of Hb. The photometer was used to screen prospective blood donors with low Hb concentration. It was possible to predict anemic subjects in the limited prospective blood donor population.     

Improved model for myocardial diffuse reflectance spectra by including mitochondrial cytochrome aa3, methemoglobin,and inhomogenously distributed RBC

The aim of this study was to compare a previously used light transport model (I) comprising the chromophores hemo‐ and myoglobin, fat, and water, with two extended models, where the chromophores of cytochrome aa3, methemo‐ and metmyoglobin are added (model II), and in addition, accounting for an inhomogenous hemoglobin distribution (model III). The models were evaluated using calibrated diffuse reflectance spectroscopy measurements on the human myocardium. Model II proved a significantly better spectral fitting, especially in the wavelength ranges corresponding to prominent absorption characteristics for the added chromophores. Model III was significantly better than model II and displayed a markedly higher tissue fraction and saturation of hemo‐ and myoglobin. The estimated tissue chromophore fractions, saturation and oxidation levels, were in agreement with other studies, demonstrating the potential of diffuse reflectance spectroscopy measurements for evaluating open heart surgery. However, the choice of chromophores and vessel packaging effects in the light transport model has a major effect on the results. (© 2011 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

Analysis of Fungal Pellets by UV-Visible Spectrum Diffuse Reflectance Spectroscopy

The application of the UV-visible spectrum diffuse reflectance spectroscopy for the determination of intracellular pH in vivo, for determination of cytochrome content, and for the noninvasive in vivo detection of the redox state of fungal mitochondrial cytochromes in filamentous fungi is introduced. The time course of the intracellular pH values, mitochondrial cytochromes, and CO-binding pigments content and the correlations between the actual redox state of cytochrome aa(3) and saturation of growth medium with oxygen in pellets of the basidiomycete Phanerochaete chrysosporium were determined. As the test microorganism, the yeast Saccharomyces cerevisiae was used. UV-visible spectrum diffuse reflectance spectroscopy proved to be a promising method for the quick and simple analysis of light-impermeable biological structures for which the classical transmittance spectrophotometric methods are difficult to implement.     

Systemic manifestations of erythema nodosum

The systemic manifestations accompanying erythema nodosum can be differentiated from those associated with the precipitating infectious process and from coincident disease processes. Erythema nodosum itself is characterized by (a) skin lesions at pressure sites, (b) malaise, fever and occasionally chills, (c) arthritis (70 per cent) and (d) over-reactivity of tissue. Tissue hypersensitivity is most pronounced at sites of trauma, at sites of specific skin testing, and in the lymphoid system draining infections in the pharynx and lung. Common infections of the respiratory tract most often antedate attacks of erythema nodosum. In New England, a beta-hemolytic streptococcus infection is a common causative factor, and tuberculosis is an unusual causative factor. In endemic areas, coccidioidomycosis is a common cause of erythema nodosum. The most important coincidental disease process is rheumatic heart disease. Rarely is it a sequel of erythema nodosum. Other "collagen diseases" may coexist with erythema nodosum. Erythema nodosum is its own most common complication. Follow-up studies indicate that over half of the patients have a subsequent attack, and a certain number have recurrent episodes for months to years. The management of erythema nodosum is expectant. In each case the cause should be found and treated. Steroid treatment is rarely justified, and should be used only after tuberculosis and other treatable entities have been ruled out.     

Psoriasis exacerbation after hormonotherapy in prostate cancer patient—Case report

Psoriasis, as the most common inflammatory skin disorder, affects about 2–3% of the world''s population. Many non-dermatological conditions have been linked with psoriasis, including cardiovascular diseases, depression, inflammatory bowel disorders, and some cancers, i.e. lung, colon and kidney cancers. Among systemic factors are endocrine and metabolic disturbances as well as many drugs. Erythrodermic psoriasis, the most severe form of the disease, is characterized by diffuse erytrema and scaling, often accompanied by fever, chills, and malaise.A 57-year-old Caucasian man was admitted for curative radiation therapy of adenocarcinoma of the prostate after 3 months of initial hormonal therapy. The management comprised the combined androgen blockade (CAB). On admission the patient reported escalation of psoriasis symptoms, which he had been treated for since 2002. Due to a mild course of the disease he had not required any systemic treatment ever before, even during aggravation periods. The last exacerbation started appearing a month after hormonal therapy implementation. The cutaneous eruptions, already existing, become larger with new foci revealing, mainly on upper and lower limbs. During radiotherapy planning, there appeared a diffuse erythema and scaling on hands and feet with accompanying pruritis. We decided to start the previously planned radiation therapy which included the prostate gland with 1.5 cm margin and provided for the total dose of 72 Gy in 36 fractions. The irradiation was conducted with the four-field technique using a megavoltage linear accelerator. During radiotherapy we photo-documented skin lesions.To our best knowledge hormone therapy (androgen deprivation) of prostate cancer patients has not been reported as an aggravating factor. Thus, the aim of our work is to present the case of a prostate cancer patient who experienced psoriasis exacerbation after implementation of hormonal blockade as a neoadjuvant oncological treatment.     

Determination of oxygen saturation and hematocrit of flowing human blood using two different spectrally resolving sensors.

The blood parameters oxygen saturation and hematocrit were determined by two different spectral sensors using reflectance spectra from 550 to 900 nm and partial transmission spectra centered at 660 nm. The spectra were analyzed by the method of partial least squares. One sensor consists of a miniature integrating sphere, while the other was fiber-guided. The results show that the geometry of the sensors and different blood flows do not influence the spectral analysis significantly. Independent of the sensor geometry, both hematocrit and oxygen saturation could be determined with an absolute predicted root mean square error of less than 3%. Furthermore, the analysis showed that hematocrit prediction requires eight wavelength regions and oxygen saturation prediction requires four wavelength regions using reflectance spectroscopy. This implies that if the measurement is restricted to reflectance, a spectrometer is indispensable for determining both blood parameters. Hematocrit determination could be improved using reflectance measurements in combination with transmission.     

Emerging role of anti-tumor necrosis factor therapy in rheumatic diseases

Tumor necrosis factor alpha (TNF-alpha) is an inflammatory cytokine that has been implicated in a variety of rheumatic and inflammatory diseases. New understanding of the importance of TNF-alpha in the pathophysiology of rheumatoid arthritis and Crohn's disease led to the development of a new class of targeted anti-TNF therapies. Anti-TNF-alpha agents including etanercept (a fusion protein of the p75 TNF receptor and IgG1) and infliximab (a chimeric monoclonal antibody specific for TNF-alpha) have been approved for the treatment of rheumatoid arthritis. In addition, infliximab has been approved in the treatment of patients with active or fistulating Crohn's disease. A new appreciation of the importance of TNF-alpha in other rheumatic and inflammatory diseases has led to a broadening of the application of anti-TNF agents. Both etanercept and infliximab have been used in open-label and randomized studies in patients with psoriatic arthritis. Although larger randomized trials are needed to confirm early results, both these anti-TNF-alpha agents, etanercept and infliximab, have demonstrated activity in improving the signs and symptoms of psoriatic arthritis and psoriasis. Infliximab has also been shown to be effective in patients with other rheumatic diseases, including ankylosing spondylitis, and may be effective in adult-onset Still's disease, polymyositis, and Beh?et's disease. Further investigations will fully elucidate the role of infliximab in these and other rheumatic diseases.     

Antibodies to cytokeratin-8 in patients with different lung pathology

Antibodies to cytokeratin-8 were detected by enzyme immunoassay (EIA) in sera of 135 patients with cryptogenic fibrosing alveiolitis, different rheumatic diseases, sarcoidosis and exogenous allergic alveolitis, 109 patients with inflammatory lung diseases and 74 donors of the Moscow Blood Transfusion Station. The results revealed that The frequency of positive EIA reactions among the donors was 7%, while in the group of patients with rheumatic diseases--from 5.9% (scleroderma) to 42.9% (fibrosing alveolitis). Positive reactions also occurred in patients with exogenous allergic alveolitis and sarcoidosis. In the group of patients with chronic inflammatory lung diseases, i.e. in pathologies of non-autoimmune origin, positive reactions occurred in 13.3-33.3% of cases. To improve diagnostics and to disclose the mechanisms of pathogenesis, more detailed study of anticytokeratin antibodies in cases of interstitial lesions and chronic inflammatory lung diseases are necessary.     

The ratio of lipidperoxides to superoxide dismutase activity in the skin lesions of patients with severe skin diseases: an accurate prognostic indicator

We studied 35 patients with active inflammatory skin diseases, measuring the levels of lipidperoxides and of the oxygen radical scavenging enzyme superoxide dismutase (SOD) in biopsy specimens of skin lesions. Lipidperoxide levels were markedly elevated in all patients. In fifteen patients with disease that was severe and highly resistant to therapy, SOD activity was only slightly increased, in comparison with normal controls. In contrast, in the twenty patients with mild disease that responded well to therapy, SOD activity was markedly elevated. The ratio of lipidperoxide levels to SOD activity was thus an accurate prognostic indicator, being elevated only in the group not responding to treatment. These findings suggest that the severity of allergic inflammatory skin disease and/or the response to treatment may in part be governed by the degree to which the patient's SOD activity is up-regulated in response to the generation of tissue-damaging substances such as lipidperoxides. Interestingly, our studies revealed the SOD activities of both normal and inflamed skin to be unexpectedly high; our data suggest that SOD plays a critical role in protecting the skin from the effects of oxygen radicals and ultraviolet light.     

Melanin quantification by in vitro and in vivo analysis of near‐infrared fluorescence

Objective measurements of melanin can provide important information for differentiating melanoma from benign pigmented lesions and in assessing pigmentary diseases. Herein, we evaluate near‐infrared (NIR) fluorescence as a possible tool to quantify melanin. Various concentrations of in vitro Sepia melanin in tissue phantoms were measured with NIR fluorescence and diffuse reflectance spectroscopy. Similar optic measurements were conducted in vivo on 161 normal human skin sites. Diffuse reflectance spectroscopy was used to quantify the melanin content via Stamatas–Kollias algorithm. At physiologic concentrations, increasing in vitro melanin concentrations demonstrated higher fluorescence that was linearly correlated (R² = 0.99, p < .001). At higher concentrations, the fluorescence signal plateaued. A linear relationship was also observed with melanin content in human skin (R² = 0.59, p < .001). Comparing the fluorescence and reflectance signals with in vitro and in vivo samples, the estimated melanin concentration in human skin ranged between 0 and 1.25 mg/ml, consistent with previous quantitative studies involving invasive methods.