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2.
Saf Health Work ; 14(1): 43-49, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36941943

ABSTRACT

Background: Messaging surrounding skin cancer prevention has previously focused on the general public and emphasized how or when activities should be undertaken to reduce solar ultraviolet radiation (UVR) exposure. Generic messages may not be applicable to all settings, and should be tailored to protect unique and/or highly susceptible subpopulations, such as outdoor workers. The primary objective of this study was to develop a set of tailored, practical, harm-reducing sun safety messages that will better support outdoor workers and their employers in reducing the risk of solar UVR exposure and UVR-related occupational illnesses. Methods: We adapted a core set of sun safety messages previously developed for the general population to be more applicable and actionable by outdoor workers and their employers. This study used an integrated knowledge translation approach and a modified Delphi method (which uses a survey-based consensus process) to tailor the established set of sun safety messages for use for outdoor worker populations. Results: The tailored messages were created with a consideration for what is feasible for outdoor workers, and provide users with key facts, recommendations, and tips related to preventing skin cancer, eye damage, and heat stress, specifically when working outdoors. Conclusion: The resulting tailored messages are a set of evidence-based, expert- approved, and stakeholder-workshopped messages that can be used in a variety of work settings as part of an exposure control plan for employers with outdoor workers.

3.
Pediatrics ; 150(2)2022 08 01.
Article in English | MEDLINE | ID: mdl-35534988

ABSTRACT

BACKGROUND AND OBJECTIVES: The worldwide severe acute respiratory syndrome coronavirus 2 pandemic challenges adolescents' mental health. In this study, we aim to compare the number of pediatric ICU (PICU) admissions after suicide attempts during the first German lockdown and one year later during a second, prolonged lockdown with prepandemic years. METHODS: A retrospective multicenter study was conducted among 27 German PICUs. Cases <18 years admitted to the PICU because of accidents or injuries between March 16 and May 31 of 2017 to 2021 were identified based on International Classification of Diseases, 10th Revision codes (German modification) and patient data entered into a database. This study is a subset analysis on suicide attempts in adolescents aged 12 to 17.9 years. The Federal Statistics Office was queried for data on fatal suicides, which were available only for 2020 in adolescents aged 10 to 17.9 years. RESULTS: Total admissions and suicide attempts declined during the first lockdown in 2020 (standardized morbidity ratio 0.74 (95% confidence interval; 0.58-0.92) and 0.69 (0.43-1.04), respectively) and increased in 2021 (standardized morbidity ratio 2.14 [1.86-2.45] and 2.84 [2.29-3.49], respectively). Fatal suicide rates remained stable between 2017 to 2019 and 2020 (1.57 vs 1.48 per 100 000 adolescent years) with monthly numbers showing no clear trend during the course of 2020. CONCLUSIONS: This study shows a strong increase in serious suicide attempts among adolescents during the course of the pandemic in Germany. More research is needed to understand the relation between pandemic prevention measures and suicidal ideation to help implement mental health support for adolescents.


Subject(s)
COVID-19 , Suicide, Attempted , Adolescent , COVID-19/epidemiology , Child , Communicable Disease Control , Humans , Intensive Care Units, Pediatric , Pandemics , Suicidal Ideation
4.
Children (Basel) ; 9(3)2022 Mar 04.
Article in English | MEDLINE | ID: mdl-35327736

ABSTRACT

Children's and adolescents' lives drastically changed during COVID lockdowns worldwide. To compare accident- and injury-related admissions to pediatric intensive care units (PICU) during the first German COVID lockdown with previous years, we conducted a retrospective multicenter study among 37 PICUs (21.5% of German PICU capacities). A total of 1444 admissions after accidents or injuries during the first lockdown period and matched periods of 2017-2019 were reported and standardized morbidity ratios (SMR) were calculated. Total PICU admissions due to accidents/injuries declined from an average of 366 to 346 (SMR 0.95 (CI 0.85-1.05)). Admissions with trauma increased from 196 to 212 (1.07 (0.93-1.23). Traffic accidents and school/kindergarten accidents decreased (0.77 (0.57-1.02 and 0.26 (0.05-0.75)), whereas household and leisure accidents increased (1.33 (1.06-1.66) and 1.34 (1.06-1.67)). Less neurosurgeries and more visceral surgeries were performed (0.69 (0.38-1.16) and 2.09 (1.19-3.39)). Non-accidental non-suicidal injuries declined (0.73 (0.42-1.17)). Suicide attempts increased in adolescent boys (1.38 (0.51-3.02)), but decreased in adolescent girls (0.56 (0.32-0.79)). In summary, changed trauma mechanisms entailed different surgeries compared to previous years. We found no evidence for an increase in child abuse cases requiring intensive care. The increase in suicide attempts among boys demands investigation.

5.
Aerosp Med Hum Perform ; 92(3): 160-166, 2021 Mar 01.
Article in English | MEDLINE | ID: mdl-33754973

ABSTRACT

BACKGROUND: The first skin physiological pilot experiment (SkinA) on a single astronaut showed a deterioration of the skin. In a follow-up experiment (SkinB) we showed that skin physiological parameters improved on average. However, it is well known that sports have positive effects on the skin, that astronauts prefer special sports devices, and do sports with different intensity. The aim of this study was to analyze the different sports activities of SkinB astronauts and to find out whether they have an influence on the skin physiological parameters.METHODS: The cumulative distance covered on the treadmill and on the cycle ergometer as well as the repetition of arm-related exercises have been calculated and possible correlation between sports activities and skin physiological parameters have been analyzed.RESULTS: The average distance covered for all six astronauts per day is 1364 AU on the treadmill T2, and 11,077 AU on the cycle ergometer CEVIS. In addition, the astronauts performed an average of about 73 repetitions of all arm-related exercises daily. Here, we were able to show very well how differently the astronauts on the ISS train. In addition, a decreasing trend in skin volume can be observed in astronauts with increasing activity on the bicycle and more repetitions on arm-related exercises.CONCLUSION: Increased activity on the cycle ergometer and increased arm-related exercises have a medium negative impact on the parameter skin volume and thus reflects more fluid content in the skin. No correlations between sports activities and skin moisture/skin barrier function could be found.Braun N, Hunsdieck B, Theek C, Ickstadt K, Heinrich U. Exercises and skin physiology during International Space Station expeditions. Aerosp Med Hum Perform. 2021; 92(3):160166.


Subject(s)
Expeditions , Space Flight , Weightlessness , Astronauts , Exercise , Humans , Skin Physiological Phenomena
6.
Skin Pharmacol Physiol ; 33(2): 77-85, 2020.
Article in English | MEDLINE | ID: mdl-31982879

ABSTRACT

BACKGROUND: Sunscreen products aim to help protect the skin against UV radiation and consequently reduce the risk of early skin ageing and skin cancer. However, it is well known that some sunscreen ingredients are not photostable, but this usually refers to irradiation with UV light. Moreover, it has to be mentioned that a relative cumulative erythema effectiveness compliant light source is used for the in vivo sun protection factor (SPF) testing. Here, UV simulators equipped with a xenon arc lamp use filters such as WG320 and UG11 (thickness 1 mm) to minimize infrared (IR) radiation and wavelength below 300 nm. However, under practical conditions, the sunscreen product is not only exposed to UVA/B light, but also to visible light (VIS) and IR light. In fact, the spectrum of solar radiation is composed of approximately 7% UV, 39% VIS and 54% IR. AIMS: To investigate the influence of short-wave and long-wave radiation on the photostability of sunscreens. METHODS: Irradiation was performed with the Suntest CPS+ that is considered to closely imitate solar radiation. The filter UG11 (thickness 1 mm), which absorbs much of the VIS and IR light, and the glass filter WG320 (thickness 2 mm), which effectively absorbs radiation of wavelengths less than 300 nm, were used in the Suntest CPS+ both individually and in combination and were inserted between the light source and the samples. The following transmission measurements were carried out with Labsphere's UV-2000s device. Here, the effectiveness (percentage change of SPF before irradiation to SPF after irradiation) as a measure of the photostability was calculated. RESULTS: As expected after total solar spectrum irradiation, the effectiveness in all tested sunscreens is lower compared to relative cumulative erythema effectiveness light used for in vitro testing of SPF. In the reference sunscreen formula S2 as well as in the two different sunscreen products, especially long-wave radiation (>400 nm) had an effect on photostability, whereas short-wave radiation had only a minor impact. In contrast, in the BASF sun care gel line only short-wave radiation below 300 nm had an effect on photostability, and blocking VIS and IR light had no effect at all. CONCLUSION: Based on these data, we can conclude that short waves and/or VIS + IR light have an influence on the photostability of sunscreens.


Subject(s)
Drug Stability , Radio Waves/adverse effects , Skin Neoplasms/drug therapy , Sun Protection Factor/standards , Sunscreening Agents/chemistry , Ultraviolet Rays/adverse effects , Humans , Photochemistry , Radiation Protection , Skin Neoplasms/etiology , Skin Neoplasms/pathology , Sunscreening Agents/administration & dosage , Sunscreening Agents/radiation effects
7.
Skin Res Technol ; 26(1): 105-111, 2020 Jan.
Article in English | MEDLINE | ID: mdl-31541489

ABSTRACT

BACKGROUND: In space, due to fluid shift a 45% decrease in the skin topography parameter volume (mm3 ) was seen using the VisioScan® camera. Simultaneously, the parameters roughness, scaling and wrinkles changed dramatically as well. Thus, the present study has the objective to understand the relationship between the SELS parameters under extreme conditions and their application by addressing scientific-dermatological questions. MATERIAL AND METHODS: SELS measurements were performed on the volar forearms of six astronauts. The Pearson correlation coefficient was used to determine the association between the variables. RESULTS: A significant correlation was found between the skin topography parameter volume and the skin parameters roughness, scaling and wrinkles. A closer look at each astronaut revealed a significant correlation for all astronauts for the parameters volume and roughness and for more than 65% of the astronauts for the parameters volume and scaling and volume and wrinkles. However, no correlation could be found between the parameters skin hydration and roughness and scaling, respectively. CONCLUSION: Only the parameter skin volume leads to meaningful data under microgravity. Physiological changes observed by fluid shift are comparable to the skin condition edema on earth. Based on the obtained data, we can conclude that the formulas for the SELS parameters roughness, scaling and wrinkles for this special skin condition need to be reviewed.


Subject(s)
Astronauts , Skin Aging/physiology , Skin/chemistry , Space Flight , Weightlessness , Forearm/physiology , Humans , Surface Properties
8.
Skin Pharmacol Physiol ; 32(5): 244-253, 2019.
Article in English | MEDLINE | ID: mdl-31330510

ABSTRACT

BACKGROUND: About 50% of the sun's radiation arriving on earth is visible light (VIS). For a long time, its effects on human health have not been fully investigated. But recently, the influence of VIS has gained more attention, especially regarding skin physiology. Studies showed various effects, many of them harmful, comparable to UV radiation. As a result, there are now a few sunscreens commercially available which claim protection against VIS. The question of whether protection is necessary is still much discussed. AIMS: The objective of this study was to develop an easy-to-perform high-energy visible (HEV) and low-end visible (LEV) light transmittance method to determine the direct VIS protection of sunscreens and other cosmetic samples. Furthermore, the influence of the brightness of the tested products on the HEV, LEV, and infrared A protection was investigated. METHODS: An experimental setup consisting of a light source, a VIS-transmissible filter system, and a sensor unit was built to measure the direct VIS protection of sunscreens and other daily skin care products in two ranges of the VIS area. For a closer look, the brightness of the samples was evaluated by photometric assessment. RESULTS/CONCLUSION: The experimental setup could be validated. It could be demonstrated for the first time that there is a strong positive linear correlation between transmittance and brightness of tinted sunscreen and daily skin care products with sunscreen properties in the HEV, LEV, and infrared A range. However, tinted samples worked best in the blue light region, and the higher the wavelength range, the lower the protection.


Subject(s)
Light , Sunscreening Agents , Infrared Rays
9.
Skin Pharmacol Physiol ; 32(1): 52-57, 2019.
Article in English | MEDLINE | ID: mdl-30485842

ABSTRACT

BACKGROUND: One of the most challenging and important factors of manned space missions is to keep astronauts healthy on orbit. In a study on 46 ISS crew members who were on 6-month (average) missions, skin rashes were the most self-reported event. Furthermore, among notable events, 40% were classified as skin rashes/hypersensitivities. Thus, especially skin conditions during space travel are of major clinical interest and require further research. AIMS: The aim of the study was to determine skin conditions in space flight among US and European astronauts, especially taking into account the terrestrial skin conditions as well as on-orbit skin care habits. METHODS: A preflight questionnaire was given to the astronauts asking about their terrestrial skin care habits and skin conditions/atopy before launch. In addition, they were asked to fill out a postflight questionnaire asking about their on-orbit skin care routine and whether any special observations regarding the skin were made during flight. RESULTS: A total of 23 skin symptoms were recorded by 8 nonatopic astronauts (mean age: 41 years) during the mission. The symptoms were peeling (21.74%), rash (17.39%), dryness (13.04%), severe dryness (8.70%), reddening (8.70%), itchiness (8.70%), bruising (4.35%), skin sensitivity (4.34%), bumps (4.35%), acne (4.35%) and slow healing of contusions and lacerations (4.35%). Especially the hands and feet were affected by skin problems. As a result of this examination, it was shown that the skin symptoms correlate with poor hygiene on orbit, whereas the factor "environment" on the ISS plays a minor role. Surprisingly, 2 astronauts even experienced positive effects on their skin. CONCLUSION: Based on these preliminary data, it is important to pay more attention to skin hygiene and maintenance in space.


Subject(s)
Astronauts , Self Report , Skin Diseases/diagnosis , Skin/pathology , Space Flight/trends , Adult , Humans , Skin Diseases/physiopathology , Time Factors
10.
Skin Pharmacol Physiol ; 32(1): 43-51, 2019.
Article in English | MEDLINE | ID: mdl-30485843

ABSTRACT

BACKGROUND: Skin reaction to spaceflight has not really been studied yet, although the skin has a very important barrier function to protect the body and can contribute to a more general understanding of physiology. It is proposed here to make a more thorough investigation of the skin during long-term spaceflight, using noninvasive techniques. AIMS: The aim of the present Skin-B study is to investigate the kinetics and range of possible skin modifications during long-duration spaceflights and their recovery. METHODS: In order to investigate the effect on skin physiological parameters during spaceflight, measurements were carried out on 6 astronauts with respect to skin hydration, transepidermal water loss/barrier function, and surface evaluation of the living skin in orbit. Additional measured parameters on the ground were skin elasticity, skin density and thickness, as well as microcirculation. RESULTS: Data from the Skin-B subjects (n = 6) contradict the results obtained in the previous pilot study SkinCare (n = 1 subject). In the present study, no deterioration of the skin was found but rather an improvement in skin hydration and skin barrier function, and no changes or improvement in the appearance of the skin surface. Furthermore, the skin density and skin thickness as well as skin elasticity values were unchanged from pre-flight values. CONCLUSION: In conclusion, we found that spaceflight under present conditions has no negative impact on skin physiological parameters.


Subject(s)
Astronauts , Elasticity/physiology , Skin/blood supply , Skin/cytology , Space Flight/trends , Water Loss, Insensible/physiology , Adult , Humans , Microcirculation/physiology , Skin Physiological Phenomena , Time Factors
11.
Skin Pharmacol Physiol ; 30(6): 284-291, 2017.
Article in English | MEDLINE | ID: mdl-28972949

ABSTRACT

BACKGROUND: Today, the sun protection factor (SPF) value of sunscreen products is determined in vivo with a standardized protocol (EN ISO 24444:2010), and the measured SPF biological end point is the visible skin erythema. However, many of the sunscreen products currently available on the market have antiphlogistic ingredients, which may potentially result in an overestimated SPF of the sunscreen. AIMS: To investigate the potential influence of the antiphlogistic ingredients panthenol and bisabolol in sunscreens on the determined SPF value in vivo. METHODS: Formulations with different concentrations of the antiphlogistic ingredients bisabolol or panthenol were tested. As a reference, a base formulation (vehicle) without antiphlogistic ingredients was used. First, the SPF of the sunscreen formulas with and without antiphlogistic ingredients was analyzed in vitro. To investigate whether the antiphlogistic ingredient may suppress the inflammatory response to ultraviolet (UV) irradiation, the SPF was determined in vivo. Finally, selected formulations were also analyzed in an erythema model for testing formulations on UV-induced inflammation. RESULTS: It could be confirmed that no differences between the formula with and that without the active antiphlogistic ingredients bisabolol or panthenol exist when measured in vitro. However, there was also no statistically significant difference in the erythemal response between the vehicle (without an antiphlogistic active ingredient) and the test formulations with different concentrations of the antiphlogistic active ingredients in the in vivo determination of the SPF. Evidence of anti-inflammatory activity of the sunscreen antiphlogistics bisabolol and panthenol was also not apparent in the UV model over a time course of 48 h. Conlusion: The antiphlogistic ingredients panthenol and bisabolol incorporated in the tested sunscreen formula do not interfere with erythema reddening and thus do not affect the SPF value in vivo.


Subject(s)
Anti-Inflammatory Agents/pharmacology , Erythema , Pantothenic Acid/analogs & derivatives , Sesquiterpenes/pharmacology , Sun Protection Factor , Sunscreening Agents/pharmacology , Adolescent , Adult , Aged , Female , Humans , Male , Middle Aged , Monocyclic Sesquiterpenes , Pantothenic Acid/pharmacology , Regional Blood Flow/drug effects , Skin/blood supply , Skin/drug effects , Ultraviolet Rays , Young Adult
12.
Skin Pharmacol Physiol ; 30(4): 171-179, 2017.
Article in English | MEDLINE | ID: mdl-28558374

ABSTRACT

BACKGROUND: Every day human skin is exposed to infrared A (IRA) radiation as part of the natural sun rays. As IRA radiation accounts for around one third of the solar radiation, it has gained great attention concerning its effects on the human body and skin. In the past few years it has been discussed controversially whether IRA radiation (of solar origin) is harmful or not. Nonetheless, there are several sunscreens on the German market that claim IRA protection for themselves. AIMS: The present study seeks to find an experimental set-up and a test procedure for the determination and quantification of direct IRA protection (realized via reflection or absorption of the IRA radiation), since to our knowledge these do not yet exist. METHODS: In this study we proved the usability of a set-up consisting of a light source, an IRA-transmissible filter system and a sensor unit, for the determination and quantification of the IRA protection of cosmetic and non-cosmetic samples. RESULTS/CONCLUSION: The applicability of the IRA emission of the light source, the spectral detector, transmissivity of the filter systems and the sample carriers could be validated. This experimental set-up can be used as an in vitro test procedure for the determination of direct IRA protection.


Subject(s)
Infrared Rays , Sunscreening Agents , Consumer Product Safety , Textiles
13.
BMC Pediatr ; 15: 18, 2015 Mar 08.
Article in English | MEDLINE | ID: mdl-25884954

ABSTRACT

BACKGROUND: Since an objective description is essential to determine infant's postnatal condition and efficacy of interventions, two scores were suggested in the past but weren't tested yet: The Specified-Apgar uses the 5 items of the conventional Apgar score; however describes the condition regardless of gestational age (GA) or resuscitative interventions. The Expanded-Apgar measures interventions needed to achieve this condition. We hypothesized that the combination of both (Combined-Apgar) describes postnatal condition of preterm infants better than either of the scores alone. METHODS: Scores were assessed in preterm infants below 32 completed weeks of gestation. Data were prospectively collected in 20 NICU in 12 countries. Prediction of poor outcome (death, severe/moderate BPD, IVH, CPL and ROP) was used as a surrogate parameter to compare the scores. To compare predictive value the AUC for the ROC was calculated. RESULTS: Of 2150 eligible newborns, data on 1855 infants with a mean GA of 28(6/7) ± 2(3/7) weeks were analyzed. At 1 minute, the Combined-Apgar was significantly better in predicting poor outcome than the Specified- or Expanded-Apgar alone. Of infants with a very low score at 5 or 10 minutes 81% or 100% had a poor outcome, respectively. In these infants the relative risk (RR) for perinatal mortality was 24.93 (13.16-47.20) and 31.34 (15.91-61.71), respectively. CONCLUSION: The Combined-Apgar allows a more appropriate description of infant's condition under conditions of modern neonatal care. It should be used as a tool for better comparison of group of infants and postnatal interventions. TRIAL REGISTRATION: clinicaltrials.gov Protocol Registration System (NCT00623038). Registered 14 February 2008.


Subject(s)
Apgar Score , Infant, Premature , Delivery Rooms , Female , Gestational Age , Humans , Infant , Infant Mortality , Infant, Newborn , Pregnancy , Prognosis , Risk Factors
14.
PLoS One ; 10(3): e0119793, 2015.
Article in English | MEDLINE | ID: mdl-25803719

ABSTRACT

Bacterial infections and inflammation of the uterus are common in dairy cattle after parturition. In particular, pathogenic bacteria that cause endometritis have been the focus of research in cattle reproduction in the last ten years. The aim of the present study was to identify commensal lactobacilli in the bovine uterus and to examine their influence on the synthesis of pro-inflammatory factors in bovine endometrial epithelial cells in vitro. Lactobacillus species were isolated from healthy bovine uteri and further characterised. Bovine endometrial epithelial cells in the second passage (n = 5 animals) were co-cultured with the autochthonous isolates L. buchneri, L. ruminis and L. amylovorus as well as with a commercially available L. vaginalis in different multiplicities of infection (MOI = 1, 5 and 10, respectively). Endometrial epithelial cells cultured without bacteria served as controls. At distinct points in time (2, 4 and 6 h) total RNA was extracted from co-cultured epithelial cells and subjected to reverse transcription quantitative PCR of pro-inflammatory factors. Furthermore, the release of such factors by co-cultured epithelial cells was measured by ELISA or EIA after 24 and 48 h. L. ruminis and L. amylovorus induced increased interleukin (IL) IL1A, IL6, IL8 and prostaglandin-endoperoxide synthase 2 mRNA levels and the release of IL8 and prostaglandin F(2α) in endometrial epithelial cells compared with control cells. In contrast, L. buchneri did not significantly influence the expression and release of these factors. Toll-like receptors 2 and 6 transcripts were found unchanged in co-cultured and untreated epithelial cells in vitro. However, endometrial epithelial cells of each animal showed individual differences in the response to bacterial load. These results suggest that Lactobacillus species are present in the bovine uterus, revealing immunomodulatory properties.


Subject(s)
Endometrium/cytology , Endometrium/microbiology , Epithelial Cells/microbiology , Lactobacillus/isolation & purification , Lactobacillus/physiology , Animals , Cattle , Cell Survival , Coculture Techniques , Cyclooxygenase 2/genetics , Epithelial Cells/cytology , Epithelial Cells/metabolism , Female , Gene Expression Regulation , Interleukins/genetics , Interleukins/metabolism , Lactobacillus/growth & development , RNA, Messenger/genetics , RNA, Messenger/metabolism , Toll-Like Receptor 2/genetics , Toll-Like Receptor 6/genetics
15.
Am J Respir Crit Care Med ; 190(5): 560-71, 2014 Sep 01.
Article in English | MEDLINE | ID: mdl-25073001

ABSTRACT

RATIONALE: Effective therapeutic interventions for chronic, idiopathic lung diseases remain elusive. Normalized T-cell function is an important contributor to spontaneous resolution of pulmonary sarcoidosis. Up-regulation of inhibitor receptors, such as programmed death-1 (PD-1) and its ligand, PD-L1, are important inhibitors of T-cell function. OBJECTIVES: To determine the effects of PD-1 pathway blockade on sarcoidosis CD4(+) T-cell proliferative capacity. METHODS: Gene expression profiles of sarcoidosis and healthy control peripheral blood mononuclear cells were analyzed at baseline and follow-up. Flow cytometry was used to measure ex vivo expression of PD-1 and PD-L1 on systemic and bronchoalveolar lavage-derived cells of subjects with sarcoidosis and control subjects, as well as the effects of PD-1 pathway blockade on cellular proliferation after T-cell receptor stimulation. Immunohistochemistry analysis for PD-1/PD-L1 expression was conducted on sarcoidosis, malignant, and healthy control lung specimens. MEASUREMENTS AND MAIN RESULTS: Microarray analysis demonstrates longitudinal increase in PDCD1 gene expression in sarcoidosis peripheral blood mononuclear cells. Immunohistochemistry analysis revealed increased PD-L1 expression within sarcoidosis granulomas and lung malignancy, but this was absent in healthy lungs. Increased numbers of sarcoidosis PD-1(+) CD4(+) T cells are present systemically, compared with healthy control subjects (P < 0.0001). Lymphocytes with reduced proliferative capacity exhibited increased proliferation with PD-1 pathway blockade. Longitudinal analysis of subjects with sarcoidosis revealed reduced PD-1(+) CD4(+) T cells with spontaneous clinical resolution but not with disease progression. CONCLUSIONS: Analogous to the effects in other chronic lung diseases, these findings demonstrate that the PD-1 pathway is an important contributor to sarcoidosis CD4(+) T-cell proliferative capacity and clinical outcome. Blockade of the PD-1 pathway may be a viable therapeutic target to optimize clinical outcomes.


Subject(s)
B7-H1 Antigen/metabolism , CD4-Positive T-Lymphocytes/physiology , Programmed Cell Death 1 Receptor/metabolism , Sarcoidosis, Pulmonary/immunology , Adult , Aged , Antibodies , B7-H1 Antigen/immunology , Biomarkers/metabolism , Case-Control Studies , Cell Proliferation , Female , Flow Cytometry , Humans , Immunohistochemistry , Lung Neoplasms/immunology , Lung Neoplasms/metabolism , Male , Middle Aged , Programmed Cell Death 1 Receptor/immunology , Remission, Spontaneous , Sarcoidosis, Pulmonary/metabolism , Up-Regulation
16.
JAMA Dermatol ; 149(9): 1040-9, 2013 Sep.
Article in English | MEDLINE | ID: mdl-23863960

ABSTRACT

IMPORTANCE: Sarcoidosis is a chronic granulomatous disease for which there are limited therapeutic options. This is the first randomized, placebo-controlled study to demonstrate that antimycobacterial therapy reduces lesion diameter and disease severity among patients with chronic cutaneous sarcoidosis. OBJECTIVE: To evaluate the safety and efficacy of once-daily antimycobacterial therapy on the resolution of chronic cutaneous sarcoidosis lesions. DESIGN AND PARTICIPANTS: A randomized, placebo-controlled, single-masked trial on 30 patients with symptomatic chronic cutaneous sarcoidosis lesions deemed to require therapeutic intervention. SETTING: A tertiary referral dermatology center in Nashville, Tennessee. INTERVENTIONS: Participants were randomized to receive either the oral concomitant levofloxacin, ethambutol, azithromycin, and rifampin (CLEAR) regimen or a comparative placebo regimen for 8 weeks with a 180-day follow-up. MAIN OUTCOMES AND MEASURES: Participants were monitored for absolute change in lesion diameter and decrease in granuloma burden, if present, on completion of therapy. OBSERVATIONS: In the intention-to-treat analysis, the CLEAR-treated group had a mean (SD) decrease in lesion diameter of -8.4 (14.0) mm compared with an increase of 0.07 (3.2) mm in the placebo-treated group (P = .05). The CLEAR group had a significant reduction in granuloma burden and experienced a mean (SD) decline of -2.9 (2.5) mm in lesion severity compared with a decline of -0.6 (2.1) mm in the placebo group (P = .02). CONCLUSIONS AND RELEVANCE: Antimycobacterial therapy may result in significant reductions in chronic cutaneous sarcoidosis lesion diameter compared with placebo. These observed reductions, associated with a clinically significant improvement in symptoms, were present at the 180-day follow-up period. Transcriptome analysis of sarcoidosis CD4+ T cells revealed reversal of pathways associated with disease severity and enhanced T-cell function following T-cell receptor stimulation. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01074554.


Subject(s)
Anti-Bacterial Agents/therapeutic use , CD4-Positive T-Lymphocytes/metabolism , Sarcoidosis/drug therapy , Skin Diseases/drug therapy , Administration, Oral , Adult , Aged , Anti-Bacterial Agents/administration & dosage , Azithromycin/administration & dosage , Azithromycin/therapeutic use , Chronic Disease , Drug Therapy, Combination , Ethambutol/administration & dosage , Ethambutol/therapeutic use , Female , Follow-Up Studies , Humans , Levofloxacin , Male , Middle Aged , Ofloxacin/administration & dosage , Ofloxacin/therapeutic use , Rifampin/administration & dosage , Rifampin/therapeutic use , Sarcoidosis/microbiology , Sarcoidosis/pathology , Severity of Illness Index , Single-Blind Method , Skin Diseases/microbiology , Skin Diseases/pathology , Transcriptome , Treatment Outcome , Young Adult
17.
J Immunol ; 190(11): 5446-53, 2013 Jun 01.
Article in English | MEDLINE | ID: mdl-23630356

ABSTRACT

Sarcoidosis pathogenesis is characterized by peripheral anergy and an exaggerated, pulmonary CD4(+) Th1 response. In this study, we demonstrate that CD4(+) anergic responses to polyclonal TCR stimulation are present peripherally and within the lungs of sarcoid patients. Consistent with prior observations, spontaneous release of IL-2 was noted in sarcoidosis bronchoalveolar lavage CD4(+) T cells. However, in contrast to spontaneous hyperactive responses reported previously, the cells displayed anergic responses to polyclonal TCR stimulation. The anergic responses correlated with diminished expression of the Src kinase Lck, protein kinase C-θ, and NF-κB, key mediators of IL-2 transcription. Although T regulatory (Treg) cells were increased in sarcoid patients, Treg depletion from the CD4(+) T cell population of sarcoidosis patients did not rescue IL-2 and IFN-γ production, whereas restoration of the IL-2 signaling cascade, via protein kinase C-θ overexpression, did. Furthermore, sarcoidosis Treg cells displayed poor suppressive capacity indicating that T cell dysfunction was a global CD4(+) manifestation. Analyses of patients with spontaneous clinical resolution revealed that restoration of CD4(+) Th1 and Treg cell function was associated with resolution. Conversely, disease progression exhibited decreased Th1 cytokine secretion and proliferative capacity, and reduced Lck expression. These findings implicate normalized CD4(+) T cell function as a potential therapeutic target for sarcoidosis resolution.


Subject(s)
CD4-Positive T-Lymphocytes/immunology , Remission, Spontaneous , Sarcoidosis, Pulmonary/immunology , T-Lymphocyte Subsets/immunology , Adult , Aged , Bronchoalveolar Lavage Fluid/cytology , Bronchoalveolar Lavage Fluid/immunology , CD4-Positive T-Lymphocytes/metabolism , Clonal Anergy/immunology , Female , Humans , Interleukin-2/metabolism , Male , Middle Aged , Receptors, Antigen, T-Cell/metabolism , Signal Transduction , T-Lymphocyte Subsets/metabolism , T-Lymphocytes, Helper-Inducer/immunology , T-Lymphocytes, Helper-Inducer/metabolism , T-Lymphocytes, Regulatory/immunology , T-Lymphocytes, Regulatory/metabolism , Young Adult
18.
J Clin Immunol ; 33(2): 446-55, 2013 Feb.
Article in English | MEDLINE | ID: mdl-23073617

ABSTRACT

RATIONALE: Sarcoidosis is a granulomatous disease of unknown etiology. Many patients with sarcoidosis demonstrate antigen-specific immunity to mycobacterial virulence factors. Th-17 cells are crucial to the immune response in granulomatous inflammation, and have recently been shown to be present in greater numbers in the peripheral blood and bronchoalveolar lavage (BAL) fluid (BALF) of sarcoidosis patients than healthy controls. It is unclear whether Th-17 cells in sarcoidosis are specific for mycobacterial antigens, or whether they have similar functionality to control Th-17 cells. METHODS: Flow cytometry was used to determine the numbers of Th-17 cells present in the peripheral blood and BALF of patients with sarcoidosis, the percentage of Th-17 cells that were specific to the mycobacterial virulence factor ESAT-6, and as well as to assess IFN-γ expression in Th-17 cells following polyclonal stimulation. RESULTS: Patients with sarcoidosis had greater numbers of Th-17 cells in the peripheral blood and BALF than controls and produced significantly more extracellular IL-17A (p = 0.03 and p = 0.02, respectively). ESAT-6 specific Th-17 cells were present in both peripheral blood and BALF of sarcoidosis patients (p < 0.001 and p = 0.03, respectively). After polyclonal stimulation, Th-17 cells from sarcoidosis patients produced less IFN-γ than healthy controls. CONCLUSIONS: Patients with sarcoidosis have mycobacterial antigen-specific Th-17 cells peripherally and in sites of active sarcoidosis involvement. Despite the Th1 immunophenotype of sarcoidosis immunology, the Th-17 cells have reduced IFN-γ expression, compared to healthy controls. This reduction in immunity may contribute to sarcoidosis pathogenesis.


Subject(s)
Antigens, Bacterial/immunology , Interferon-gamma/biosynthesis , Sarcoidosis/immunology , Sarcoidosis/metabolism , Th17 Cells/immunology , Adult , Bronchoalveolar Lavage Fluid/cytology , Bronchoalveolar Lavage Fluid/immunology , Case-Control Studies , Female , Humans , Immunophenotyping , Interleukin-17/metabolism , Male , Middle Aged , Receptors, Antigen, T-Cell, gamma-delta/metabolism , Th1 Cells/immunology , Th17 Cells/metabolism
19.
Int J Pediatr Otorhinolaryngol ; 76(2): 169-73, 2012 Feb.
Article in English | MEDLINE | ID: mdl-22169464

ABSTRACT

OBJECTIVE: To evaluate parental knowledge regarding household food and non-food choking hazards. DESIGN: Cross Sectional Survey. SETTING: Tertiary Care Children's Hospital. PARTICIPANTS: Parents presenting to a Pediatric Otolaryngology Clinic with a child <4 years old. METHODS: Parental survey asking which choking hazard foods (CHF) they allow their child to eat, previous instruction of CHF, knowledge of non-food choking hazards, and their knowledge sources. STATISTICS: adjusted odds ratios (AOR) and logistic regressions. RESULTS: 492 respondents. Adjusted for significant covariates associations between correct knowledge of CHF and correct parents actions of disallowing CHF: fruit chunks (prior instruction=42%; correct action=25%; AOR=3.51; P<0.0001), hot dogs (59%; 28%; 1.75; 0.0178), raw vegetables (41%; 47%; 1.28; 0.198) popcorn (67%; 49% 2.64; <0.0001), whole grapes (68%; 51%; 2.2; <0.0001), nuts (73%; 66%; 2.47; <0.0001), chunks of peanut butter (45%; 79%; 2.55; 0.0003), sticky candy (79%; 80%; 2.16; <0.0033), gum (72%; 84%; 1.75; 0.028), seeds (65%; 87%; 1.4; 0.247), 76% always supervise meals, 57% always cut food, 62% know CPR. KNOWLEDGE OF NON-FOOD HAZARDS: Coins (97%), marbles (94%), small batteries (93%), small toy parts (93%), dice (92%), pen caps (92%), safety pins (85%), balloons (84%), syringes (40%). Sources of choking hazard knowledge: physicians (67%), family/friends (52%), books/magazines (40%), and the Internet (25%). CONCLUSIONS: Parental knowledge of CHF is incomplete. The consumption of CHF in children under 4 is significantly associated with decreased parental knowledge. Therefore, more parental education is needed.


Subject(s)
Airway Obstruction/prevention & control , Food/adverse effects , Health Knowledge, Attitudes, Practice , Household Articles , Parents/education , Adult , Age Distribution , Airway Obstruction/epidemiology , Child, Preschool , Cross-Sectional Studies , Female , Health Education/methods , Hospitals, Pediatric , Humans , Incidence , Infant , Male , Parent-Child Relations , Primary Prevention/methods , Sex Distribution , Surveys and Questionnaires
20.
Arch Otolaryngol Head Neck Surg ; 137(12): 1251-7, 2011 Dec.
Article in English | MEDLINE | ID: mdl-22183907

ABSTRACT

OBJECTIVES: To determine whether laryngeal electromyography (LEMG) can predict recurrent laryngeal nerve function return in children and whether LEMG can aid in the management of vocal fold immobility (VFI). DESIGN: Prospective case series. SETTING: Tertiary pediatric aerodigestive centers. PATIENTS: Twenty-five children aged 14 days to 7 years at the time of first LEMG (mean age, 21.4 months) with VFI who underwent flexible fiberoptic laryngeal examination, intraoperative LEMG of the thyroarytenoid muscles, and 12-month follow-up. MAIN OUTCOME MEASURES: To compare results of LEMG with flexible fiberoptic laryngeal examination in children with vocal fold paresis and to determine if LEMG can predict vocal fold return. RESULTS: In children who had a patent ductus arteriosus ligation, the LEMG data suggest that if there is no activity 6 months after injury, then the nerve is unlikely to regain function. In 3 of 3 children with central causes of VFI, normal LEMG findings predicted return of nerve function 2 to 7 months before vocal fold movement on fiberoptic examination. Finally, in 3 of 3 children with idiopathic VFI, LEMG predicted return within 2 to 14 months of vocal folds with normal findings. CONCLUSIONS: Intraoperative LEMG is a safe, easy-to-use method for determining the likelihood of recurrent laryngeal nerve function return in children who have undergone patent ductus arteriosus ligation, in children with centrally correctable lesions, and in children with idiopathic VFI. More work is needed in the area of pediatric LEMG, but it is possible that LEMG data can be used to aid in management strategies and provide families with more information to make better informed decisions regarding their child's care.


Subject(s)
Electromyography/methods , Monitoring, Intraoperative/methods , Vocal Cord Paralysis/diagnosis , Brain Diseases/surgery , Child , Child, Preschool , Ductus Arteriosus, Patent/surgery , Evoked Potentials, Motor/physiology , Female , Heart Defects, Congenital/surgery , Humans , Infant , Infant, Newborn , Laryngeal Muscles/innervation , Laryngoscopy , Longitudinal Studies , Male , Postoperative Complications/etiology , Postoperative Complications/physiopathology , Postoperative Complications/surgery , Predictive Value of Tests , Prognosis , Recurrent Laryngeal Nerve/physiopathology , Tracheoesophageal Fistula/surgery , Vocal Cord Paralysis/etiology , Vocal Cord Paralysis/physiopathology
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