A pilot comparison study of four clinician-rated atopic dermatitis severity scales.

BACKGROUND: There are multiple severity outcome measures for atopic dermatitis (AD). There is a need to compare the reliability of these measures. OBJECTIVES: To compare the inter-rater and intrarater reliability of the objective Scoring Atopic Dermatitis (oSCORAD), Eczema Area and Severity Index (EASI), Six Area, Six Sign Atopic Dermatitis (SASSAD) and Three Item Severity index (TIS); and to analyse the correlation between these outcome measures and the quality-of-life instruments Patient-Orientated Eczema Measurement, Dermatology Life Quality Index and Skindex-29. METHODS: Twelve patients with AD attended a 1-day scoring exercise by five trained dermatology clinicians. Inter-rater and intrarater reliability were assessed using the intraclass correlation coefficient (ICC). Correlation between clinician-rated and patient-reported measures was analysed using Spearman's rho. RESULTS: Regarding inter-rater reliability, EASI and SASSAD showed good reliabilities, with ICCs of 0·730 [95% confidence interval (CI) 0·500-0·900] and 0·680 (95% CI 0·440-0·880), respectively. However, the ICCs were poor for TIS and oSCORAD, with 0·497 (95% CI 0·233-0·785) and 0·498 (95% CI 0·234-0·785), respectively. Separate body surface area (BSA) component analyses showed that the oSCORAD BSA component contributed to its inter-rater variations. Regarding intrarater reliability, EASI and TIS showed excellent ICCs of 0·886 (95% CI 0·744-0·952) and 0·820 (0·614-0·923), respectively, while SASSAD showed a good reliability with an ICC of 0·720 (95% CI 0·424-0·878). However, the intrarater ICC was poor for oSCORAD, with 0·446 (95% CI 0·037-0·730). Regarding correlation with patient-reported measures, only SASSAD demonstrated moderate correlation with Skindex-29 (ρ = 0·611, P = 0·035). CONCLUSIONS: EASI demonstrated the highest inter-rater and intrarater reliability, supporting it as the optimal AD severity outcome measure.

The development and validation of the treatment of autoimmune bullous disease quality of life questionnaire, a tool to measure the quality of life impacts of treatments used in patients with autoimmune blistering disease.

BACKGROUND: Treatments for autoimmune blistering diseases have significant risk of medical complications and quality of life impacts during treatment, and it is difficult to differentiate these impacts from disease burden or the effects of treatment. OBJECTIVES: To develop a quality of life instrument specific to the effects of treatments used in patients with autoimmune bullous disease (AIBD). METHODS: A comprehensive item generation process was used to build a 45-item pilot Autoimmune Bullous Disease Quality of Life (ABQOL) questionnaire, distributed to 70 patients with AIBD. Experts in bullous disease refined the pilot ABQOL, selecting only those questions pertaining to the treatment effects. This pilot Treatment of Autoimmune Bullous Disease Quality of Life (TABQOL) questionnaire was administered to 70 patients, before factor analysis was performed to yield the final questionnaire of 17 questions. Validity and reliability were evaluated across a range of indices. RESULTS: Face and content validity were established through a comprehensive patient interview process, expert review and summaries of treatments used. The questionnaire was found to have appropriate correlation with the Dermatology Life Quality Index (r = 0.64) and the level of treatments used (P < 0.01), and was found to be responsive to overall variations in treatment burden. The TABQOL was also found to be a reliable instrument as evaluated by internal consistency (Cronbach α = 0.892) and test-retest reliability (r = 0.99). CONCLUSIONS: We have shown that the TABQOL questionnaire is a valid and reliable instrument that may to be used to measure treatment burden in AIBD and serve as an end point in clinical trials.

Normalization of essential-fatty-acid-deficient keratinocytes requires palmitic acid.

Cultured adult human keratinocytes show accelerated growth rates in medium that is essential fatty acid deficient. The cells also show decreased amounts of the essential fatty acids 18:2, 20:3, and 20:4 and contain increased amounts of the monounsaturated fatty acids 16:1 and 18:1. These lower levels of polyunsaturated fatty acids were only partially restored by supplementing the medium with 18:2 and 20:4 fatty acid. The addition of the non-essential fatty acid 16:0 (5 microM), along with the essential fatty acids, resulted in the successful normalization of the major fatty acids in the deficient keratinocytes. Normalized cells showed a constant total fatty acid/mg of protein in the phospholipid fraction, as the total cell fatty acid content per cell increased with augmenting fatty acid supplementation. Supplementation of the medium with 16:0 and essential fatty acids decreased the growth and passage potential of the cells. Use of 18:1 in lieu of 18:2 fatty acid yielded essential-fatty-acid-deficient keratinocyte growth values. Likewise the least supplemented medium (5 microM 18:2 + 5 microM 16:0) also gave the accelerated cell growth rates. This study shows that manipulation of the essential fatty acid levels, if accompanied by 5 microM 16:0 in the growth medium, alters the growth properties of adult human primary keratinocytes.

Oleic acid and linoleic acid are the major determinants of changes in keratinocyte plasma membrane viscosity.

Keratinocytes were grown in medium with no essential fatty acids as well as in media with specially selected fatty acid augmentations. Gas chromatographic determinations of 21 fatty acids in the phospholipids were correlated with plasma membrane viscosity obtained by electron paramagnetic resonance studies (n = 24). Using standard procedures from multivariate analysis, we derived an expression that modeled the viscosity data as a function of four key fatty acid levels: [formula see text] where the fatty acids are given in mole percent of total lipids and are identified as two number sequences: number of carbons followed by number of double bonds. No other fatty acid made a significant contribution to the regression equation. The range of viscosity was very large, varying from 60 to 120 cP over the sample population. The results are interpreted to indicate that polyunsaturated fatty acids are replaced with monounsaturated fatty acids by the keratinocytes and that dihomogamma-linolenic acid (20:3, n-6) plays an important role in membrane viscosity when essential fatty acids are available in the growth medium of these adult human cultured keratinocytes.

In vitro model of essential fatty acid deficiency.

The polyunsaturated fatty acids linoleic acid (18:2, n-6) and arachidonic acid (20:4, n-6) are essential for normal skin function and structure, both as eicosanoid precursors and as components of lipids forming cell membranes. Adult human keratinocytes grow optimally in serum-free medium (MCDB 153) that contains no fatty acids. These keratinocytes expand rapidly and produce normal epidermis upon in vivo grafting. Analysis of lipid extracts of epidermis and of cultured keratinocytes was done to determine the fatty acid composition of cells grown in essential fatty acid (EFA)-deficient medium. Gas chromatography and high-performance liquid chromatography analyses were done of the fatty acids in the entire cell and in a thin-layer chromatography separated fraction containing those lipids that form cellular membranes. Comparison of snap-frozen epidermis and epidermal basal cell suspensions to passage 1 to 4 cultures shows that the cells are in an extreme essential fatty acid-deficient state by the first passage. The amount of the saturated fatty acids 16:0, 18:0, and 14:0 is unchanged by culture. The polyunsaturated fatty acids are found to be significantly decreased, the cells balancing their lack with a significant increase in the relative abundance of the monounsaturated fatty acids, 18:1 and 16:1. Greater than 85-90% of the fatty acids was found in lipids associated with membranes and no unusual fatty acids were detected. Because the serum-free medium is fatty acid free and the cells cannot synthesize essential fatty acids, the rapid division of the cells results in the predominance of an extreme EFA-deficient cell type. The essential fatty acid-deficient keratinocyte is an excellent adult, normal epidermal cell model that can be used to study EFA deficiency and the effect of the eicosanoid and fatty acids on cell function and structure.

Can simulation measurements be used to predict the irradiated lung volume in the tangential fields in patients treated for breast cancer?

A simple method of estimating the amount of lung irradiated in patients with breast cancer would be of use in minimizing lung complications. To determine whether simple measurements taken at the time of simulation can be used to predict the lung volume in the radiation field, we performed CT scans as part of treatment planning in 40 cases undergoing radiotherapy for breast cancer. Parameters measured from simulator films included: (a) the perpendicular distance from the posterior tangential field edge to the posterior part of the anterior chest wall at the center of the field (CLD); (b) the maximum perpendicular distance from the posterior tangential field edge to the posterior part of the anterior chest wall (MLD); and (c) the length of lung (L) as measured at the posterior tangential field edge on the simulator film. CT scans of the chest were performed with the patient in the treatment position with 1 cm slice intervals, covering lung apex to base. The ipsilateral total lung area and the lung area included within the treatment port were calculated for each CT scan slice, multiplied by the slice thickness, and then integrated over all CT scan slices to give the volumes. The best predictor of the percent of ipsilateral lung volume treated by the tangential fields was the CLD. Employing linear regression analysis, a coefficient of determination r2 = 0.799 was calculated between CLD and percent treated ipsilateral lung volume on CT scan. In comparison, the coefficients for the other parameters were r2 = 0.784 for the MLD, r2 = 0.071 for L, and r2 = 0.690 for CLD x L. A CLD of 1.5 cm predicted that about 6% of the ipsilateral lung would be included in the tangential field, a CLD of 2.5 cm about 16%, and a CLD of 3.5 cm about 26% of the ipsilateral lung, with a mean 90% prediction interval of +/- 7.1% of ipsilateral lung volume. We conclude that the CLD measured at the time of simulation provides a reasonable estimate of the percent of the ipsilateral lung treated by the tangential fields. This information may be of value in evaluating the likelihood of pulmonary complications from such treatment and in minimizing toxicity.

Human stratified squamous epithelia differ in cellular fatty acid composition.

The phospholipid component of the cellular membrane is crucial to the structure and function of cells. Basal cells from three epithelial tissues, adult human skin epidermis, oral mucosa, and hair follicles, grow rapidly in serum- and lipid-free medium. Analysis of phospholipid extracts from the above three types of stratified squamous epithelium in both in vivo and in vitro was done to relate fatty acid cell composition to cell function. The fatty acid composition of hair follicles in vivo was analyzed in plucked scalp hairs, and those of skin epidermis and oral mucosa in vivo were analyzed after separating the tissue into suprabasal and basal layers. The fatty acid composition of the in vivo cells from hair follicles shows a partial essential fatty acid (EFA)-deficient state. There was no significant difference between the skin epidermis and the oral mucosa in the fatty acid composition of the in vivo cells from each basal layer. However, in the suprabasal layers, the percent of linoleic acid (18:2) from the skin epidermis was higher than that from the oral mucosa. This study shows that total fatty acid composition in cell membranes of stratified squamous epithelium varies with their keratinization pattern. When cultured, the three types of rapidly growing keratinocytes showed the same essential fatty acid deficient pattern in the membrane phospholipids.

The effect of three Korean traditional medicines on the growth rate of cultured human keratinocytes.

The effect of three different Korean Traditional Medicines (KTM) was studied on several functional parameters of adult human cells in culture. The cells were non-transformed strains of normal, skin epidermal cells (keratinocytes) from adult humans. Aqueous extracts of the herbal medicines were tested using two types of cell strains: one type was essential fatty acid deficient (EFAD) cells which grow rapidly in medium that was low in calcium and had no essential fatty acids; the second type was a cell strain grown in medium supplemented with essential fatty acid (EFA-supplemented). These cells had much slower, in vivo skin growth rates, and the fatty acid composition resembled that measured in epidermal biopsy tissue. The KTMs chosen for this study were tae-gang-hual-tang (for treating osteoarthritis), hual-ak-tang (for pain relief) and sip-zeon-tae-bo-tang (for fortifying immune systems). Because high proliferation rates usually correlate with skin inflammation and because many of the chemotactic agents mediating inflammatory response are modified fatty acids, this study focused on cell growth rate and membrane fatty acid composition as signals for the effects of the herbal medicines. By monitoring growth rate, these experiments measured both a stimulatory and a regulatory effect on the growth of keratinocytes. Some toxicity was seen at the highest doses of the KTMs. These effects were modeled mathematically, and the results showed varying effects on growth rate depending on dose and herbal recipe. The fitting parameters were discussed as they relate to biological function. The experimental design was also discussed and alternatives were suggested.

Social climate perception and depression of patients and staff in a chronic hemodialysis unit.

This socioecological study investigates the relationship of depression and social climate perception of patients (N = 59) and staff N = 18) in a chronic hemodialysis unit. The Beck Depression Inventory (BDI) and Moos Ward Atmosphere Scale (WAS) Form C revised for dialysis are used for measurement. Patients and staff are found to have significantly dissonant perception of the unit. Patients perceive the environment more negatively than the staff. Depressed patients correlate with Low WAS scores (p less than .03) indicating that depression influences social climate perception. Depressed patient BDI items are correlated with WAS items via a series of Pearson correlation coefficients for a perceptual profile. Discussion is made as to the dysfunctional affects of dissonance, depression, staff denial and withdrawal. Further studies on altering the social ecology of dialysis units as a method for reducing depression and staff turnover rates are called for.

The Tecumseh study of respiratory illness. VII. Further observations on the occurrence of respiratory syncytial virus and Mycoplasma pneumoniae infections.

The occurrence of infection with respiratory syncytial (RS) virus and Mycoplasma pneumoniae was determined over a 6-year period among residents of Tecumseh, Michigan by isolation and serology. RS virus infection was detected for a variable time each year during the months extending from November to May. There was little viral activity in intervals between these periods of prevalence, which occurred on an alternating short-long cycle. Higher infection rates were detected in periods preceding the long interval than were detected in periods preceding the short interval. Viruses isolated from serial annual outbreaks did not show any sequential changes in antigens, although some variation in antigenic structure was apparent. Infections were common in school-age children, indicating the role of this population in transmission. Young girls were infected as often as young boys, suggesting that observed differences in occurrence of illness must be related to differences in expression of infection. In contrast to RS virus, M. pneumoniae did not appear and disappear annually, but like it, the school-age group was most heavily involved in infection.

Anterior segment abnormalities in cicatricial retinopathy of prematurity.

Abnormalities that occur in the anterior segments of patients with retinopathy of prematurity have been studied in 72 eyes of 36 patients. The anterior chamber depth, the placido disc image on the cornea, the distortion of polarized light by corneal stress, and keratometry readings were recorded. There was a highly significant correlation between anterior chamber depth, retinopathy of prematurity, and keratometry readings (p less than .001). These findings emphasize the importance of careful follow-up examinations of the anterior segment in retinopathy of prematurity because cataracts, band keratopathy, acute hydrops, and angle-closure glaucoma can progressively occur as complications.

Epidermal keratinocytes actively maintain their intracellular polyamine levels.

Increased cellular polyamine levels are thought to be essential for epidermal keratinocyte proliferation. However, a number of studies report that the induction of keratinocyte proliferation and of ornithine decarboxylase, the rate-limiting enzyme of putrescine, spermidine and spermine biosynthesis, is not concordantly expressed. The relationship between epidermal keratinocyte polyamine synthesis and proliferation was studied in neonatal mouse keratinocyte cultures using specific inhibitors of ODC activity to decrease the intracellular polyamine levels. The ODC inhibitors alpha-methyl ornithine (alpha-Me-Orn), alpha-hydrazino ornithine (alpha-HO) and difluoro-alpha-methylornithine (alpha-DFMO) did not significantly inhibit epidermal keratinocyte proliferation at 5 X 10(-3) to 10(-4) M concentrations. At these doses, only alpha-DFMO was seen to decrease (by 70%) the cellular levels of putrescine, but not of spermidine or spermine. Epidermal keratinocyte growth in the higher dose of 20 mM alpha-DFMO, however, did not decrease the cellular levels of putrescine. Polyamine analyses of the spent medium showed that growth in 10 mM alpha-DFMO decreased the normal epidermal cell transport of putrescine and spermidine into the medium. At 20 mM alpha-DFMO concentration, the keratinocytes actually transported, intracellularly, the putrescine and spermidine that are naturally found in the foetal bovine component of the growth medium. We conclude from these studies that epidermal keratinocyte polyamine levels are determined by both the rate of synthesis, and of the transport of these amines into the extracellular medium. Since epidermal keratinocytes actively maintain specific polyamine levels, it appears that these molecules are essential for epidermal keratinocyte function.