bluuebunny/crossref_metadata_2025 huggingface dataset:
Rhinovirus Is Associated with Severe Asthma Exacerbations and Raised Nasal Interleukin-12
Authors: Ferreira Alet , Williams Zelda , Donninger Howard , van Schalkwyk Emmerentia M. , Bardin Philip G.
Published: April 2003

Background: Rhinovirus (RV) is associated with asthma exacerbations in longitudinal studies, but the role in patients with acute severe asthma who require admission to a hospital emergency room remains to be fully defined. The cytokines interleukin-10 (IL-10) and IL-12 may be elevated or suppressed by viral infections and contribute to a worsening of airway inflammation in asthmatics. Objectives: We assessed the association of RV with acute severe asthma and nasal IL-10 and IL-12. Methods: Patients admitted to a hospital emergency asthma service had nasal aspirates (NAs) taken and peak expiratory flow (PEF) measured on admission and again 7, 28 and 56 days after admission. RV was sought in all NAs using a validated polymerase chain reaction assay and IL-10 and IL-12 were measured on admission and after 56 days in a subgroup of 22 asthmatics and 6 normal controls. Results: Thirty-seven asthmatics with a reduced PEF (% predicted) of 50.4 ± 2.5% (mean ± SEM) on admission were studied. RV was detected in NAs of 13 patients (35%) on admission, in 6 of the 13 patients after 7 days (16%), in 1 patient after 28 and 56 days and was absent in controls. IL-10 was not increased on admission or after 56 days. Measurements of IL-12 were raised on admission compared to 56 days later in asthmatics with RV detectable (p = 0.04). In asthmatics without RV, nasal IL-12 levels were correlated with PEF measurements over this period (r = 0.5, p < 0.05). Conclusions: A temporal relationship between the presence of nasal RV and emergency room admission for acute severe asthma was found in one third of patients. Low levels of IL-10 during RV infections could contribute to unopposed synthesis of pro-inflammatory cytokines whilst increases in IL-12 may amplify nasal and endobronchial inflammation.
Direct Demonstration of the Productive Capability of Cytokines at the Single Cell Level in Lung Sarcoidosis Using Multicolor Cytometry
Authors: Kunisawa Akira , Kawanishi Yoshikazu , Tago Hidekazu , Nagate Akira , Kasuga Ikuma , Ohyashiki Kazuma
Published: April 2003

Background: Sarcoidosis is a chronic systemic disorder of unknown etiology characterized by noncaseating epithelioid cell granulomatous lesions, around which an increasing number of CD4+ T cells infiltrate. These CD4+ T cells may release interferon-γ (IFN-γ) and interleukin-2 (IL-2). These cytokines are considered to play an important role in pathogenesis of sarcoidosis. Methods: We employed a modification of Jung’s method using multicolor flow cytometry to assess the capability of single cells obtained from bronchoalveolar lavage (BAL) fluid to produce various cytokines. BAL CD4+ T cell production of IFN-γ, IL-2 and IL-4 after phorbol ester and ionomycin stimulation were studied. Results: The percentage of IFN-γ- and IL-2-producing CD4+ T cells was significantly higher in patients with sarcoidosis compared to healthy volunteers [84.7 ± 7.5 vs. 51.2 ± 14.8% (p < 0.005), and 75.3 ± 8.7 vs. 39.8 ±11.0% (p < 0.001), respectively]. No significant difference in the percentage of IL-4-producing CD4+ T cells was noted (1.2 ± 0.6 vs. 3.5 ± 2.6%; not significant), whereas the absolute number of IL-4-producing CD4+ T cells was significantly higher in patients with sarcoidosis compared to healthy volunteers (563.6 ± 330.2 vs. 50.9 ± 66.9/ml; p < 0.005). In the IL-4-producing CD4+ T cells, about 80% of cells concomitantly produced IFN-γ and more than 60% of cells also produced IL-2. Conclusion: We demonstrate that Th1-like-producing cells are predominant in the CD4+ as well as in the CD8+ T cell subset of patients with sarcoidosis. We for the first time demonstrated concomitant capabilities of BAL CD4+ T cells to produce Th1 and Th2 cytokines at the single cell level by multicolor flow cytometry.
Intermittent Positive Airway Pressure by Nasal Mask as a Treatment for Respiratory Insufficiency in a Patient with Syringomyelia
Authors: Verbraecken Johan , Willemen M. , de Cock W. , Van de Heyning P. , de Backer W.
Published: April 2003

We report a case of a 73-year-old woman with chronic respiratory failure in association with syringohydromyelia and sleep apnea. She was initially intubated and mechanically ventilated. Weaning from the ventilator was only successful after nasal intermittent positive airway pressure therapy was started. A normalization of arterial blood gas exchange could be achieved.
Protective Effects of (–)-Epigallocatechin-3-Gallate on UVA- and UVB-Induced Skin Damage
Authors: Kim Jongil , Hwang Jae-Sung , Cho Youn-Ki , Han Yongku , Jeon Young-Jin , Yang Kyu-Hwan
Published: April 2003

It has been known that green tea and its components possess significant chemopreventive effects against chemical carcinogens and photo-caused skin tumor formation. In this study, the protective effects of (–)-epigallocatechin-3-gallate (EGCG), a major green tea catechin, on the ultraviolet (UV)-induced skin damage (photoaging) were studied in guinea pigs, hairless mice and human dermal fibroblast cultures. The lipid peroxidation was significantly reduced in the EGCG-treated group. The amount of lipid peroxides produced in the control and EGCG treated group were 838 ± 144 and 286 ± 57 nmol/mg at 18 h after UV irradiation, respectively. UVB-induced erythema was also significantly reduced in the EGCG treated group. The erythema relative index of the control and the EGCG treated group were 311 ± 45 and 191 ± 49 at 16 h after UV irradiation, respectively. EGCG treatment reduced UVA-induced skin damage (roughness and sagginess) and protected from the decrease of dermal collagen in hairless mouse skin. EGCG treatment blocked the UV-induced increase of collagen secretion and collagenase mRNA level in fibroblast culture. The nuclear transcription factors NF-ĸB and AP-1 binding activities were also inhibited by EGCG treatment.
Differences in the Two-Dimensionally Measured Laser Doppler Flow at Different Skin Localisations
Authors: Stücker M. , Steinberg J. , Memmel U. , Avermaete A. , Hoffmann K. , Altmeyer P.
Published: April 2003

The cutaneous microcirculation shows a significant heterogeneity. With high-resolution two-dimensional laser Doppler perfusion imaging (LDPI), spatial and temporal reproducible perfusion measurements can be reached. The objective of this study was the quantification of skin perfusion in 20 defined skin areas with LDPI, in 60 healthy young and old volunteers. The perfusion of the face was significantly higher than that of the trunk and extremities. The highest perfusion values were seen at the lips, 1.47 arbitrary units (AU), followed by the chin (0.99 AU), the nose (0.95 AU), the forehead (0.73 AU) and the cheek (0.72 AU). Mean perfusion, between 0.40 and 0.49 AU, was seen at the extremities and at the trunk. The lowest perfusion was found at the bottom (0.37 AU), on the back of the foot (0.36 AU) and on the soles (0.31 AU). There was a tendency to show higher perfusion values in men than in women (0.60 ± 0.31 vs. 0.53 ± 0.26 AU). Age-related differences in perfusion could not be demonstrated. In the evaluation of the perfusion of pathological skin, regional perfusion differences must be considered, whereas moderate age or gender differences between different investigation groups can be tolerated.
Cutaneous Photochemoprotection by Green Tea: A Brief Review
Authors: Ahmad Nihal , Mukhtar Hasan
Published: April 2003

Alarmingly increasing incidences of skin cancer are being reported from many countries where the majority of the population is Caucasian. According to projected estimates by the American Cancer Society, approximately 1.3 million cases of basal-cell and squamous-cell cancers, grouped together as nonmelanoma skin cancers, are diagnosed annually in the USA alone. It is clear that excessive exposure of the skin to solar radiation, particularly the UVB component, is responsible for these cancers. It is also important to mention here that among all the cancers, skin cancer is believed to be one of the most preventable and curable cancer types. While the surgical therapy for these skin cancers is highly effective, because of their recurrence and many other reasons, these cancers cause significant morbidity to the patients. One way to reduce the occurrence of these cancers is through chemoprevention. For the chemoprevention of photodamage and thus for photocarcinogenesis, we will use the term ‘photochemoprotection’. In recent years, the naturally occurring compounds, especially the antioxidants, present in the common diet and beverages consumed by the human population have gained considerable attention as chemopreventive agents for potential human benefit. Many such agents have found a place in skin care products. Green tea, rich in polyphenolic antioxidants, is gaining increasing attention as a supplement in skin care products. In this short review, we will discuss the chemopreventive potential of green tea polyphenols against skin cancer, especially photocarcinogenesis. We advocate that the use of skin care products supplemented with agents such as green tea in conjunction with the use of sunscreens and educational efforts may be an effective strategy for reducing UV-induced photodamage and skin cancer in humans.
Azelastine Tablets in the Treatment of Chronic Idiopathic Urticaria
Authors: Camarasa J.M.G. , Aliaga A. , Fernández-Vozmediano J.M. , Fonseca E. , Iglesias L. , Tagarro I.
Published: April 2003

This trial was designed to study the efficacy and tolerability of azelastine in controlling symptoms of chronic idiopathic urticaria, using ebastine as validation group. Fifty-two adult patients were randomised to receive azelastine (4 mg), ebastine (10 mg) or 18 placebo for 21 days. Patients were required to visit the investigating physicians on three different occasions (days 0, 7 and 21). On each of these three study days, investigators assessed itching, wheals and erythema, based on a 4-point scale, and quality of life using a visual-analogue scale and subscale 9 of the Short Form 36 (SF-36) Health Survey. Patients entered daily assessments of itching on diary cards also using a 4-point scale. Furthermore, investigators assessed global efficacy and tolerability of the study medication on day 21 or upon premature discontinuation of the trial. Side effects and compliance were evaluated on each visit. A statistically significant reduction in itching was found for both active treatments compared with placebo. These improvements, which were statistically significant already after 1 day of treatment, continued over the course of 3 weeks. Additionally, both azelastine and ebastine were effective in improving symptoms such as wheals and erythema when compared to placebo. The quality-of-life parameters were unaffected by either treatment. Taste perversion (2 cases) and somnolence (1 case) were the only adverse drug reactions of azelastine. Ebastine, however, seemed to cause more often and more severe symptoms such as fatigue, sleepiness and asthenia. Global assessments of efficacy and tolerability performed by the investigators, also favoured azelastine. In conclusion, both azelastine and ebastine are effective and safe drugs, able to control symptoms of chronic idiopathic urticaria since the first day of treatment, and along a period of 3 weeks.
The Relationship between Neutrophils and Incisional Wound Healing
Authors: Cantürk Nuh Zafer , Esen Nilüfer , Vural Birol , Cantürk Zeynep , Kirkali Guldal , Oktay Gulgun , Solakoglu Seyhun
Published: April 2003

The systemic administration of granulocyte-macrophage colony-stimulating factor (GM-CSF) is used clinically to increase circulating neutrophils, but its wound healing effects after intraperitoneal treatment have not been studied yet. We planned to investigate the effect of neutrophils on wound healing under cyclophosphamide and GM-CSF treatment. Forty rats were divided into three groups: control group (group I, n = 12) receiving saline, group II (n = 14) receiving cyclophosphamide and group III (n = 14) receiving GM- CSF. The rats in all groups underwent incisional wounding and were euthanized after 7 days. Blood neutrophil counts and functions, tensile strengths and the hydroxyproline level of skin were determined, and a histopathological evaluation of healing was made. Neutrophil counts and phagocytosis significantly increased in group III and decreased in group II. Although the skin hydroxyproline level did not differ, there was a difference in tensile strength of the wounded skin between group II and group III. The wound score in group II was lower than that in groups III and I. As a result we suggest that systemically given GM-CSF – by increasing the neutrophil count and neutrophil phagocytosis index – can enhance the tensile strength of surgical incisions.
EEMCO Guidance for the Assessment of Transepidermal Water Loss in Cosmetic Sciences
Authors: Rogiers Vera
Published: April 2003

Measurement of transepidermal water loss (TEWL), based on the estimation of the water vapour gradient in an open chamber, is being used to support claims of cosmetics including product mildness, reduction in irritative skin reactions, skin hydration, skin repair, protective effect against UV damage and others. TEWL measurement can also screen ingredients that have a beneficial effect on the barrier function and offer the possibility to monitor in vivo, on human skin, the effect of topical treatment in an objective and non-invasive way. A high number of variables affecting TEWL measurements have been identified. These should be rigorously taken into consideration. To work under standardised conditions is of the utmost importance to obtain reliable and reproducible results.
New Developments in the Treatment of Psoriasis
Authors: van de Kerkhof P.C.M.
Published: April 2003

During the previous 10 years, important innovations have been developed in the treatment of psoriasis. Calcipotriol has been introduced in most countries already 10 years ago and more recently 2 other vitamin D3 analogues have become available: calcitriol and tacalitol. In some countries, the topical retinoid tazarotene has been registered as a routine treatment in psoriasis. Evidence-based data on the efficacy and safety of combination treatments are accumulating. In particular, the combination of calcipotriol and topical corticosteroids has been shown to be very effective and safe. The combination of systemic treatments is controversial. In individual patients, the risk of combining major therapies should be balanced against the need to enhance efficacy in individuals. New leads in experimental treatments are new vitamin D3 analogues and new retinoids as well as 4-hydroxylase- and 24-hydroxylase inhibitors. Important innovations in immunomodulatory treatments are: tacrolimus, ascomycine, anti-CD4, anti-CD25, peptide T and LFA3TIP.
Assessment of ‘Dry Skin’: Current Bioengineering Methodsa nd Test Designs
Authors: Fischer Tobias W. , Wigger-Alberti Walter , Elsner Peter
Published: April 2003

Dry skin is a frequent problem in dermatology and a sign of dysfunction of the epidermis, especially of the stratum corneum as the morphological equivalent of the skin barrier. It may occur as an individual disposition or as the leading symptom of atopic dermatitis or ichthyosis. Besides the visual examination of the skin, various bioengineering methods have been developed to assess the different pathological and adaptive changes in the skin. In addition to the assessment of skin humidity, barrier function and desquamation, the quantification of skin surface topography and the mechanical properties of skin are suitable methods to characterize a dry skin condition. For clinical assessment of moisturizing products and emollients the parameters of investigation have to be defined and integrated in an adapted study design depending on the composition and content of the active agent in the test product. Newly developed cosmetic products have to be investigated for safety and efficacy. Modern bioengineering methods are suitable to fulfill these challenges.
Sphingolipid Signaling in Epidermal Homeostasis
Authors: Geilen Christoph C. , Barz Steffen , Bektas Meryem
Published: April 2003

In the present review we have attempted to give an overview of the role of sphingolipids in skin homoeostasis. Sphingolipid metabolites are emerging as potent second messengers in diverse cellular signaling pathways. In the skin little is known about sphingolipids in signaling events. In various cell populations it has been shown that different sphingolipid metabolites have opposing effects on the biological outcome of a stimulus. Therefore, the term ‘sphingolipid rheostat’ has been established and has also been shown to exist in skin-derived cell populations. In many cells ceramide is a mediator of proliferation inhibition and apoptosis, whereas sphingosine-1-phosphate acts more like a growth factor and reverses ceramide effects. In keratinocytes extracellular and intracellular ceramides play important roles. Extracellular ceramides are necessary for the water retention capacity and for maintaining the permeability barrier of the skin. Intracellular ceramides cause differentiation of keratinocytes. Until now less is known about the effect of other sphingolipid metabolites in the skin.
Epidemiology of Cutaneous Melanoma in Germany and Worldwide
Authors: Garbe Claus , Blum Andreas
Published: April 2003

Rising incidence rates of cutaneous melanoma have been observed during the last three decades. At the beginning of the 1970s 3 cases and in the 1990s 9 cases per 100,000 inhabitants and year were reported by the Saarland Cancer Registry in Germany. Other incidence studies from Germany in the 1990s even reported 10–12 cases per 100,000 inhabitants and year, which is more likely to be the representative melanoma incidence in Western Germany. In a worldwide comparison this is a medium incidence rate as compared to clearly higher incidence rates in the United States (10–20 cases per 100,000 inhabitants and year) and in Australia (40–60 cases per 100,000 inhabitants and year). In Europe the highest incidence rates have been reported from Scandinavia (about 15 cases per 100,000 inhabitants and year) and the lowest from the Mediterranean countries (about 5–7 cases per 100,000 inhabitants and year). Mortality rates likewise increased in Germany between 1970 and 1995 in males from 1.7 to 3.2 cases and in females from 1.6 to 2.0 cases per 100,000 inhabitants and year. In the 1990s, in Germany and in many other countries a leveling off of mortality rates was observed. 48,928 melanoma patients have been recorded by the Central Malignant Melanoma Registry from the German-speaking countries in the time period from 1983 to September 2000, and clinico-epidemiological analysis of cutaneous melanoma is based on this data material. While 2/3 of all melanoma patients in Germany were females in the 1970s, there is now a more balanced gender distribution with more than 45% of patients being males. Age distribution does not significantly change during the last three decades. Most melanomas are diagnosed in the age group between 50 and 60 years, 22% of all melanomas are diagnosed before the 40th year of age. A clear decrease of Breslow’s tumor thickness was found from the beginning of the 1980s to the mid-1990s with the median thickness decreasing from 1.3 to 0.8 mm. Lower Breslow’s tumor thickness at first diagnosis of cutaneous melanoma has only been reported from Australia. This development indicates improved early recognition of cutaneous melanoma which is presently the main factor for a more favorable prognosis.
Enhancement of the Antiparakeratotic Potency of Calcitriol and Tacalcitol in Liposomal Preparations in the Mouse Tail Test
Authors: Körbel J.N. , Sebök B. , Kerényi M. , Mahrle G.
Published: April 2003

In order to test the advantage of vitamin D3 preparations in liposomal form, calcitriol, the natural activated form of vitamin D3, and tacalcitol, a vitamin D3 analogue, were employed in various concentrations and using different vehicles in the mouse tail test, an animal model for testing the antiparakeratotic efficacy of topical medications. The optimal concentration in petrolatum turned out to be similar to that in commercial preparations. The liposomal preparations were superior to those in petrolatum and to those in nonliposomal phospholipids. The antiparakeratotic potency (drug activity) of liposomal tacalcitol in a concentration of 2 µg/g was twice that of the commercial preparation with a higher concentration of 4 µg/g. These results suggest that the use of liposomal vitamin D3 preparations can achieve a given antipsoriatic effect with a reduced concentration of the active substance thereby reducing the risk of skin irritation and of hypercalcemia.
Retinoids – Which Dermatological Indications Will Benefit in the Near Future?
Authors: Zouboulis Christos C.
Published: April 2003

Retinoids are compounds with pleiotropic functions and a relatively selective targeting of certain skin structures. They are vitamins, because retinol (vitamin A) is not synthesized in the body and must be derived from diet, but also hormones with intracrine activity, because retinol is transformed into molecules that bind to nuclear receptors, exhibit their activity, and are subsequently inactivated. Retinoids exert their effects on target cells by binding and activating nuclear retinoid receptors. Retinoid receptors bind their ligands in form of dimers. Heterodimers can be formed between two different retinoid receptor molecules but also between retinoid X receptors and the vitamin D receptor as well as the triiodothyronin receptor. This fact indicates complex interactions between retinoids and further hormonal signal transduction molecules. Interaction of retinoid receptors with transcriptional factors activated by other signal transduction mechanisms, e.g. AP-1, may provide dissociation of the retinoid effects. Retinoids can exhibit agonistic activity but also be neutral antagonists and inverse agonists. Topical and oral retinol, tretinoin, isotretinoin, and bexarotene, topical alitretinoin, retinaldehyde, motretinide, adapalene, tazarotene, and systemin acitretin compose the list of launched retinoids. Psoriasis and related disorders, congenital disorders of keratinization, acne, photoaging and hypovitaminosis A are classical approved indications of retinoid treatment, whereas cutaneous T-cell lymphoma, AIDS-associated Kaposi’s sarcoma, acute promyelocytic leukemia and actinic lentigines were currently confirmed. In addition, retinoids have been successfully used in several other dermatoses, e.g. epithelial precanceroses and tumors, seborrhea, rosacea and acneiform dermatoses, lichen planus, eosinophilic folliculitis, condylomata accuminata, lichen sclerosus and atrophicus. Highly receptor selective molecules, retinoic acid receptor-β-inducers, AP-1 complex antagonists, and inverse agonists will be probably lead the retinoid development in the near future. New, more effective and less toxic retinoids, alone or in combination with other drugs and new delivery systems may provide therapeutic solutions for benign and malignant proliferative skin diseases, such as psoriasis and non-melanoma tumors, cancer chemoprevention and differentiation therapy.
Skin Manifestations in Solid Organ Transplant Recipients
Authors: Tsambaos D. , Badavanis G.
Published: April 2003

The clinical spectrum of the most significant dermatological complications of solid organ transplantations is presented in an attempt to enhance the awareness among dermatologists and other physicians of the importance of careful dermatological monitoring of organ transplant recipients for early diagnosis and prompt treatment of these manifestations.
Stem Cells in the Epidermis
Authors: O’Shaughnessy Ryan F.L. , Christiano Angela M.
Published: April 2003

The epidermis consists of three actively proliferating units, the interfollicular epidermis, the hair follicle, and the sebaceous gland. Stem cells in the epidermis have the capacity to produce all three of these units. The fate of the epidermal stem cells and some of their progeny can be altered, dependent on the environment in which they reside and the genes they express. In this review, we describe the major experiments that have contributed to the understanding of the epidermal stem cells and the control of their fate.
Chemoprevention of Basal Cell Carcinomas in the ptc1+/– Mouse – Green and Black Tea
Authors: Hebert Jennifer L. , Khugyani Farishta , Athar Mohammad , Kopelovich Levy , Epstein Jr. Ervin H. , Aszterbaum Michelle
Published: April 2003

Skin cancers are a rising menace as their incidence increases, attributed in part to increasing ultraviolet radiation exposure. This increasing problem has stimulated efforts to devise useful preventive approaches. The uncertain efficacy of exhortations to avoid sun exposure and to use protective clothing and sunscreens to reduce damage when exposed argue for the development of an oral chemopreventive agent. Bickers and others have studied the effects and mechanisms of tea and of its putative active components on inhibition of skin cancer in experimental models. To continue this work, we have studied the effects of oral green tea and black tea on a new model of ultraviolet-induced skin carcinogenesis – the development of basal cell carcinomas in ptc1+/– mice. To our surprise, we have found that tea preparations which others have used to prevent squamous cell carcinoma formation in mice fail to inhibit basal cell carcinogenesis in our model, suggesting that prevention of this cancer may require special, tumor-specific approaches.
Host Defense Mechanisms in Polyaromatic Hydrocarbon Carcinogenesis
Authors: Elmets Craig A. , Katiyar Santosh K. , Xu Hui , Mukhtar Hasan
Published: April 2003

Polyaromatic hydrocarbons (PAHs) are chemicals that are widely employed to examine the complex mechanisms by which chemicals cause cancer. While it is clear that the tumors that carcinogenic PAHs produce elicit an immune response, the interplay between host immune defense mechanisms and earlier stages in the cutaneous carcinogenesis pathway has received little attention. Studies from our laboratories have shown that topical application of several different PAHs to mice results in the development of an antigen-specific cell-mediated immune response to them. The response is genetically determined and is mediated by CD8+ T cells. Development of a cell-mediated immune response is associated with resistance to dimethylbenz(a)anthracene tumorigenesis. These findings are consistent with the hypothesis that host defense mechanisms against PAHs help to protect individuals from the carcinogenic actions of these agents. This may form the basis for novel immunopreventive strategies for individuals at high risk for development of tumors produced by PAHs.
The Skin: Target Organ in Immunotoxicology of Small-Molecular-Weight Compounds
Authors: Merk Hans F. , Sachs Bernhard , Baron Jens
Published: April 2003

Immunotoxicology studies two different effects of xenobiotics: immunosuppression and dysregulation of immune responses leading to hypersensitivity or autoimmunity. The skin is a major target organ of immunotoxicity which is provoked by small-molecular-weight compounds. Methods may be helpful for immunotoxicological investigations and screenings for adverse effects of xenobiotics which are used for diagnosis or studies on the pathophysiology of skin disorders such as allergic contact dermatitis, cutaneous drug-allergic reactions or autoimmune diseases of the skin. Examples include well-designed patch tests, assays involving antigen-presenting cells such as dendritic cells, but also T lymphocytes, basophiles or keratinocytes.
Investigation of Follicular Penetration of Topically Applied Substances
Authors: Lademann J. , Otberg N. , Richter H. , Weigmann H.-J. , Lindemann U. , Schaefer H. , Sterry W.
Published: April 2003

The influence of specific follicle properties, sebum production and hair growth on the follicular penetration of topically applied substances was investigated. The behavior of follicles identified in selected skin areas of volunteers was analyzed by various tape stripping and staining methods in combination with laser scanning microscopy. Furthermore hair growth in the selected skin areas was determined. A correlation between sebum production, hair growth activity and follicular penetration was observed.
Development of a Low-Metal Adhesive Tape to Detect and Localize Metals in or on the Stratum corneum at Parts per Million Levels
Authors: Cullander C. , Grant P.G. , Bench G.
Published: April 2003

Tape-stripping is a well-established method for sampling the stratum corneum (SC). We have developed a tape with low-metal content suitable for use with particle-induced X-ray emission (PIXE), an analytical technique based on X-ray spectrometry. PIXE analysis of tape-stripped samples of SC is a reliable and minimally invasive means of identifying and quantifying metals present at parts per million levels. Assay feasibility and reproducibility was demonstrated using human volunteers. This new tape-strip technique has potential applications in exposure and decontamination assessment, diagnosis of metal dermatitis, forensics, and in environmental research.
New Aspects of the Skin Barrier Organization
Authors: Bouwstra J. , Pilgram G. , Gooris G. , Koerten H. , Ponec M.
Published: April 2003

In the superficial layer of the skin, the stratum corneum (SC), the lipids form two crystalline lamellar phases with periodicities of 6.4 and 13.4 nm (long-periodicity phase). The main lipid classes in SC are ceramides, free fatty acids and cholesterol. Studies with mixtures prepared with isolated ceramides revealed that cholesterol and ceramides are very important for the formation of the lamellar phases, and the presence of ceramide 1 is crucial for the formation of the long-periodicity phase. This observation and the broad-narrow-broad sequence of lipid layers in the 13.4-nm phase led us to propose a molecular model for this phase. This consists of one narrow central lipid layer with fluid domains on both sides of a broad layer with a crystalline structure. This model is referred to as ‘the sandwich model’. While the presence of free fatty acids does not substantially affect the lipid lamellar organization, it is crucial for the formation of the orthorhombic sublattice, since the addition of free fatty acids to cholesterol/ceramide mixtures results in transition from a hexagonal to a crystalline lipid phase. Studies examining lipid organization in SC derived from dry or lamellar X-linked ichthyosis skin revealed that in native tissue the role of ceramide 1 and free fatty acids is similar to that observed with mixtures prepared with isolated SC lipids. From this we conclude that the results obtained with lipid mixtures can be used to predict the SC lipid organization in native tissue.
Assessment of Topical Bioavailability in vivo: The Importance of Stratum corneum Thickness
Authors: Kalia Y.N. , Alberti I. , Naik A. , Guy R.H.
Published: April 2003

We present a method to determine the cutaneous bioavailability and hence to evaluate the bioequivalence of topically applied drugs in vivo. The procedure uses serial tape-stripping and transepidermal water loss measurements to quantify the thickness of the removed stratum corneum (SC) and to determine the intact membrane thickness. Following tape-stripping, the drug is extracted from the tapes and assayed, e.g., by HPLC. This provides a drug concentration profile as a function of the normalized position within the SC. The data are fitted to a solution of Fick’s second law of diffusion in order to calculate characteristic membrane transport parameters. Integration of the concentration profile over the entire SC thickness, that is, the ‘area-under-the-curve’, provides a measure of the cutaneous bioavailability and hence can be used to assess the bioequivalence of topically applied drugs.
Oxidative Targets in the Stratum corneum
Authors: Thiele J.J.
Published: April 2003

As the outermost layer of skin, the stratum corneum (SC) is continuously exposed to an oxidative environment, including air pollutants, ultraviolet radiation, chemical oxidants, and aerobic microorganisms. Human SC reveals characteristic antioxidant and protein oxidation gradients with increasing antioxidant depletion and protein oxidation towards the outer layers. SC antioxidants, lipids, and proteins are oxidatively modified upon treatments with ultraviolet A/ultraviolet B, ozone, and benzoyl peroxide. α-Tocopherol represents the predominating SC antioxidant with respect to its concentration and its unique susceptibility to the various oxidative challenges tested. In sites rich in sebaceous glands, α-tocopherol is physiologically delivered to the surface via secretion of sebum. Oxidative damage in the human SC represents an early pathophysiological event preceding barrier disruption and inflammation in environmentally challenged skin. Furthermore, oxidative gradients in SC proteins may have implications for the process of desquamation in human skin.
The Human Stratum corneum Layer: An Effective Barrier against Dermal Uptake of Different Forms of Topically Applied Micronised Titanium Dioxide
Authors: Pflücker F. , Wendel V. , Hohenberg H. , Gärtner E. , Will T. , Pfeiffer S. , Wepf R. , Gers-Barlag H.
Published: April 2003

Electron microscopy visualisation and light microscopic investigations of three different application forms of titanium dioxide proved that neither surface characteristics, particle size nor shape of the micronised titanium dioxide result in any dermal absorption of this substance: Micronised titanium dioxide is solely deposited on the outermost surface of the stratum corneum and cannot be detected in deeper stratum corneum layers, the human epidermis and dermis.
Gamma Knife Radiosurgery for Large Volume Brain Tumors: An Analysis of Acute and Chronic Toxicity
Authors: Linzer D. , Ling S.M. , Villalobos H. , Raub Jr W. , Wu X. , Ting J. , Berti A. , Landy H. , Markoe A.M.
Published: April 2003

Gamma Knife radiosurgery is often used to treat intracranial tumors <4 cm (approximately 13.5 cm3) in mean diameter. Larger lesions are rarely treated because of the expectation that increasing target volume will increase toxicity. We retrospectively analyzed 35 patients with primary or metastatic brain tumors of more than 13.5 cm3 treated with the Gamma Knife. Only 3 (8.5%) patients developed acute clinical toxicity. Nine (25%) patients developed post-Gamma Knife radionecrosis based on imaging studies, with only 3 of these patients (9% of the study population) having clinical progression of symptoms. Necrosis was not found to be related to prescribed dose, treatment volume or number of treated isocenters. We found no undue toxicity from the treatment of large brain tumors with the Gamma Knife.
Four Years’ Experiences in the Treatment of Pituitary Adenomas with Gamma Knife Radiosurgery
Authors: Lim Y.L. , Leem W. , Kim T.S. , Rhee B.A. , Kim G.K.
Published: April 2003

To determine the tumor control rates and endocrinological responses after stereotactic radiosurgery for pituitary adenomas, we reviewed our experience in 65 patients (40 men, 25 women) treated in the Gamma Knife during the last 4 years. The mean age was 41.6 years (range 19–69 years). 43 patients had endocrinologically active tumors (20 growth hormone-secreting, 19 prolactin-secreting and 4 ACTH-secreting adenomas). 22 had nonfunctioning adenomas. 39 patients had a macroadenoma and 26 patients had a microadenoma. 33 patients underwent Gamma Knife radiosurgery for recurrent or residual tumors after microsurgery. 50 patients have had follow-up neuroimaging studies and/or hormonal evaluation. The follow-up period was 25.5 months (range 3 to 54 months). The margin of the tumor was incorporated within the 50 to 90% isodose. The mean number of isocenters was 3.8 and the mean marginal dose was 25.4 Gy (range 15 to 36 Gy). 27 out of 40 patients (65.7%) showed decreased tumor volume to less than 50% of the initial volume. In 17 out of 38 patients (44.7%) with endocrinologically active tumors, the hormonal level fell to within the normal range. Two patients had delayed complications: in one case there was pituitary insufficiency and in the other a visual disturbance. Gamma Knife radiosurgery seems to be effective adjuvant therapy for pituitary adenoma in selected cases. More long-term follow-up is required to evaluate the efficacy and side effects further.
Pituitary Tumors and Gamma Knife Surgery - Clinical Experience with More Than Two Years of Follow-Up
Authors: Martinez R. , Bravo G. , Burzaco J. , Rey G.
Published: April 2003

30 patients with pituitary tumors were treated in our unit and followed for 26–45 months. 14 patients had nonsecreting adenomas, 7 had acromegaly, 5 had prolactinomas, 3 had Cushing''s disease. One patient had a choristoma of the pituitary stalk. The patient with a choristoma, 7 patients with nonsecreting adenomas, 4 with acromegaly, 1 prolactinoma and 3 with Cushing’s disease had been operated by transsphenoidal microsurgery prior to Gamma Knife (GK) treatment. From this group, one patient with a nonsecreting adenoma and two with acromegaly had undergone fractional external radiotherapy after surgery. Stereotactic MRI localization had been used in all cases. All the tumors showed either a reduction in volume or cessation of growth; 85% of the patients with acromegaly showed normalization of growth hormone (GH) levels. Normalization of ACTH levels occurred in the 3 patients with Cushing’s disease. All the patients with prolactinomas showed reduction of prolactin levels but normalization did not occur. However, in 3 cases the bromocriptine could be withdrawn. Deterioration of vision was not observed. One patient suffered transient paresis of the third cranial nerve that improved with steroids. Panhypopituitarism appeared in one case of Cushing’s disease two years after the treatment. In the remaining cases there were no changes in their previous physiological pituitary function. We conclude that GK radiosurgery in pituitary tumors is an effective alternative to transsphenoidal microsurgery when compression of surrounding structures does not exist, and it can efficiently replace conventional irradiation.
Protection of Visual Pathway in Gamma Knife Radiosurgery for Craniopharyngiomas
Authors: Chung W.Y. , Pan H.C. , Guo W.Y. , Shiau C.Y. , Wang L.W. , Wu H.M. , Lee L.S.
Published: April 2003

Craniopharyngiomas present a major challenge to Gamma Knife radiosurgery (GKRS) due to their proximity to the optic apparatus. Based on observations of the evolving tumoral change on MRI and clinical results, an optimization of the treatment strategy and dose selection is possible. From March 1993 to September 1996, 21 patients with craniopharyngiomas were treated by GKRS. Every patient received stereotactic MRI exclusively for targeting and dose planning. The tumor and adjacent structures, including optic nerves, chiasm, and tracts were carefully identified and delineated on sagittal, coronal and axial films. The tumor volume ranged from 0.3 to 28 ml (average 9 ml). We purposefully apply multiple isocenters (average 9.1 shots) to create an isodose curve that covered the tumor optimally while sparing the optic pathway. The marginal dose prescribed was 9.5 to 16 Gy (50%). The maximal dose was 19 to 32 Gy. The maximal dose to the optic apparatus was 3.2 to 12.5 Gy. After GKRS, all patients were followed up clinically every month. MR studies were conducted every six months with the same techniques on the same scanner to investigate evolution of tumor volume and any adverse radiation effect. The follow-up period ranged from 6 to 40 months (mean: 18.4, median: 19). All patients were followed more than 6 months. Nineteen out of 21 cases (90.5%) achieved tumor control; that is, 18 tumor shrinkage (volume reduction: 15–95%) and 1 stabilized tumor growth. Among these 21 patients, 7 had improved visual acuity or visual field after GKRS, and the rest remained stable. Two patients developed mild T2 change on MRI without any endocrinological disturbance or visual impairment. Protection of the visual pathway can be secured by a sophisticated delineation on 3-dimensional stereotactic images with multiple-shot dose planning. Craniopharyngiomas with tumor volume up to 25 ml were treated safely and effectively, because the dose to the optic apparatus was kept as low as possiby this strategy. Further follow-up is needed to determine the highest tolerable dose to surrounding critical structures and the long-term outcome of tumor control.
Leksell Gamma Knife Radiosurgery of the Tumor Glomus Jugulare and Tympanicum
Authors: Liščák R. , Vladyka V. , Šimonová G. , Vymazal J. , Janoušková L.
Published: April 2003

We have treated 14 patients with glomus tumor during the 4 years (of 1993 to 1997) using Leksell Gamma Knife radiosurgery. The male: female ratio was 1:3.7, and the mean age 48.6 years (range 22–75 years). The mean tumor volume was 5.5 cm3 (range 0.7–11.3 cm3). The mean maximum dose was 37.4 Gy (range 20–44 Gy). The mean margin dose was 19.4 Gy (range 10–25 Gy). In 3 patients, infrabasal spread of the tumor could not be delineated on peroperative stereotactic CT scans. As a result, this portion of the tumor was treated in 2 patients at a second stage using stereotactic MRI. Follow-up in 11 patients ranged from 6 to 42 months (mean 20.5 months). Hearing on the affected side was further impaired in 3 patients. Tinnitus, vertigo and ataxia improved in 3 patients, headache and nausea in 2 patients. Angiography after radiosurgery was performed in 3 patients. In one patient 12 months after the radiosurgery, pathological vascularisation had completely disappeared. In another patient pathological vascularisation was still present 22 months after the first stage, despite two-stage radiosurgery, although the tumor volume decreased 30%. In the last patient, vascularisation and tumor volume partially decreased 12 months after radiosurgery. The volume of the tumor decreased in 4 patients. No change in tumor volume has been observed in any of the other patients to date. Radiosurgery proves to be a safe treatment for glomus tumor with no acute morbidity. Because of its naturally slow growth rate, up to 10 years follow-up will probably be necessary to establish the therapeutic effectiveness of radiosurgery for glomus tumor.
Effect of Gamma Knife Radiosurgery on Rat Brain Sodium Channel Subunit mRNA Expression
Authors: Bartolomei F. , Massacrier A. , Rey M. , Viale M. , Régis J. , Gastaldi M. , Cau P.
Published: April 2003

Several lines of evidence underscore a possible and delayed antiepileptic effect of Gamma Knife irradiation. This effect could be related to structural and molecular changes. Since voltage-gated Na+ channels (NaChs) play a crucial role in neuron excitability, we studied the effect of Gamma Knife (GK) irradiation on the distribution of Na+ channel (NaCh) subunit mRNAs in rat brains. A left side irradiation was performed in rats using a stereotactic device adapted for GK radiosurgery. A dose of 100 Gy was administered with the 4 mm collimator. The left dentate gyrus and thalamus coordinates were based on De Groot’s rat stereotactic atlas. The isodose curve distribution was calculated with the dose planning software used in Gamma Knife and superimposed on the target. Na+ channels α unit and mRNAs (subtype II and subtype III) expression was studied 1 hour, 30 days and 60 days later. We used non-radioactive in situ hybridization with subtype-specific digoxigenin-labeled cRNA probes. Labeling intensity was evaluated with a densitometric analysis of digitized images from the control side (right) and lesioned side (left) in each rat. No morphological changes were observed one hour after GK irradiation. 30 days later, the upper thalamic nuclei exhibited a few necrotic regions associated with gliosis. In contrast, no lesions were observed in the hippocampus. 60 days later, the necrotic region involving thalamic nuclei was enlarged. NaCh II and III mRNAs expression did not appear to be modified after GK at the three times studied here. In particular, neurons surrounding the GK necrosis continued to express high levels of NaCh mRNAs. Thus, regulation of NaCh II and III subtypes do not appear to explain the functional antiepileptic effect of GK.
Electromyography during Stereotactic Pallidotomy for Parkinson’s Disease
Authors: Landy Howard J. , Weiner William J. , Calancie Blair , Harris William , Shulman Lisa M. , Singer Carlos , Abrams Lisa , Bowen Brian
Published: April 2003

In stereotactic pallidotomy for Parkinson’s disease, care must be taken to avoid internal capsule injury while maximizing improvement of rigidity and tremor. In 21 patients, intraoperative electromyography (EMG) was used to assess stimulation thresholds required for capsular responses and to monitor muscle tone and tremor. Surface EMG electrodes were placed on the face and multiple muscle groups of the extremities. The stimulation and lesion electrode was introduced via MRI-guided stereotaxis toward a point 2–3 mm anterior to the midcommissural point, 5–6 mm inferior to the AC-PC plane, and 21–22 mm lateral to the midline. Exact targets were modified according to MRI-visualized anatomy. With stimulation at 5 and 50 Hz, thresholds for detection of EMG responses were usually seen at 4–5 mA. EMG responses were consistently seen prior to visual observation of muscle activity. Timing of EMG response relative to stimulus aided in differentiating stimulus-related movement from spontaneous tremor. Resting spontaneous EMG activity was seen to decrease as rigidity was improved by incremental lesion production. EMG activity related to tremor was recorded; tremor decrease by lesion production was documented by EMG recording. Patient cooperation with physiologic testing during stimulation and lesion production may become limited. Intraoperative EMG monitoring provides an adjunct to improve reliability of assessment of capsular stimulation and rigidity while providing documentation of lesion impact on rigidity and tremor.
The Idea of Stereotaxy toward Minimally Invasive Neurosurgery
Authors: Ohye Chihiro
Published: April 2003

The idea of stereotaxy in modern neurosurgery is reviewed. Stereotactic surgery has been one of the particular neurosurgical techniques mainly used for functional disorders. Nowadays, it is widely used in the field of general neurosurgery owing to the rapid development of computer-assisted 3D brain images. Functional neurosurgery itself is also changing in the sense that many alternative surgical procedures are now available due to the progress in neuroscience. The original premise of stereotaxy is exactly the same as that of minimally invasive neurosurgery today.