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Henzi BC, Putananickal N, Schmidt S, Nagy S, Rubino-Nacht D, Schaedelin S, Amthor H, Childs AM, Deconinck N, Horrocks I, Houwen-van Opstal S, Laugel V, Lobato ML, Osorio AN, Schara-Schmidt U, Spinty S, von Moers A, Lawrence F, Hafner P, Dorchies OM, Fischer D. Safety and efficacy of tamoxifen in non-ambulant patients with Duchenne muscular dystrophy: a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial (TAMDMD Group B). Neuromuscul Disord 2025; 47:105275. [PMID: 39879732 DOI: 10.1016/j.nmd.2025.105275] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2024] [Revised: 01/06/2025] [Accepted: 01/06/2025] [Indexed: 01/31/2025]
Abstract
Most patients with Duchenne muscular dystrophy (DMD) are non-ambulant. Preserving proximal motor function is crucial, rarely studied. Tamoxifen, a selective oestrogen receptor modulator, reduced signs of muscular pathology in a DMD mouse model. Our objective was to assess the safety and efficacy of tamoxifen over 48 weeks in non-ambulant DMD patients. In this multicentre, randomised, double-blind, placebo-controlled, phase 3 trial at six European centres boys aged 10-16 years with genetically diagnosed DMD, non-ambulant and off corticosteroid treatment for ≥6 months, randomly assigned (1:1) to either 20 mg/day tamoxifen orally or placebo were included. The primary outcome was change in D2 motor function measure from baseline to week 48. Of 15 non-ambulant male patients with DMD screened, 14 were enrolled from January 24th, 2019, to January 6th, 2021. Eight patients were randomised to the treatment and six to the placebo group. The primary efficacy outcome did not differ significantly between tamoxifen and placebo (7.8 percentage points, 95 % CI, -26.82 to 11.22, p=0.359) with a trend not favouring tamoxifen. No deaths or life-threatening serious AEs occurred. Tamoxifen was safe but due to insufficient clinical evidence, it cannot be recommended as a treatment option for DMD. Trial registration: ClinicalTrials.gov (NCT03354039).
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Affiliation(s)
- Bettina C Henzi
- Division of Neuropediatrics and Developmental Medicine, University Children's Hospital Basel (UKBB), University of Basel, Basel, Switzerland; Division of Neuropediatrics, Development and Rehabilitation, Department of Pediatrics, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
| | - Niveditha Putananickal
- Division of Neuropediatrics and Developmental Medicine, University Children's Hospital Basel (UKBB), University of Basel, Basel, Switzerland
| | - Simone Schmidt
- Division of Neuropediatrics and Developmental Medicine, University Children's Hospital Basel (UKBB), University of Basel, Basel, Switzerland
| | - Sara Nagy
- Department of Neurology, University Hospital Basel, University of Basel, Basel, Switzerland
| | - Daniela Rubino-Nacht
- Division of Neuropediatrics and Developmental Medicine, University Children's Hospital Basel (UKBB), University of Basel, Basel, Switzerland
| | - Sabine Schaedelin
- Department of Clinical Research, University of Basel and University Hospital Basel, Basel, Switzerland
| | - Helge Amthor
- Service de Neurologie et Réanimation Pédiatriques, APHP Paris Saclay, Hôpital Raymond Poincaré, 92380, Garches, France
| | | | - Nicolas Deconinck
- Department of Paediatric Neurology and Neuromuscular Reference Center, Hôpital Universitaire des Enfants Reine Fabiola (HUB), Université Libre de Bruxelles, Brussels, Belgium
| | - Iain Horrocks
- Royal Hospital for Children, Glasgow, United Kingdom
| | - Saskia Houwen-van Opstal
- Department of Rehabilitation, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, the Netherlands
| | - Vincent Laugel
- Department of Pediatric Neurology, Strasbourg University Hospital, Strasbourg, France
| | - Mercedes Lopez Lobato
- Sección de Neurología Pediátrica, Hospital Universitario Virgen del Rocío, Sevilla, España
| | - Andrés Nascimento Osorio
- Neuromuscular Unit, Department of Neurology, Hospital Sant Joan de Déu and Center for Biomedical Research Network on Rare Diseases (CIBERER), ISCIII, Barcelona, Spain
| | - Ulrike Schara-Schmidt
- Department of Pediatric Neurology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
| | - Stefan Spinty
- Alder Hey Children's Hospital, Liverpool, United Kingdom
| | - Arpad von Moers
- Department of Pediatrics, DRK Kliniken Berlin Westend, Berlin, Germany
| | | | - Patricia Hafner
- Division of Neuropediatrics and Developmental Medicine, University Children's Hospital Basel (UKBB), University of Basel, Basel, Switzerland
| | - Olivier M Dorchies
- School of Pharmaceutical Sciences, University of Geneva, Switzerland; Institute of Pharmaceutical Sciences of Western Switzerland, University of Geneva, Switzerland
| | - Dirk Fischer
- Division of Neuropediatrics and Developmental Medicine, University Children's Hospital Basel (UKBB), University of Basel, Basel, Switzerland.
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Zheng YP, He XF, Zhang YF, Geng LX, Zhang HM, Wan H, He X. Five-blade scratcher for treating severe rhinophyma: A retrospective study. World J Clin Cases 2024; 12:4180-4190. [PMID: 39015915 PMCID: PMC11235531 DOI: 10.12998/wjcc.v12.i20.4180] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/22/2024] [Revised: 05/21/2024] [Accepted: 05/23/2024] [Indexed: 06/30/2024] Open
Abstract
BACKGROUND Rhinophyma, a late-stage subtype of rosacea, is characterized by excessive sebaceous glands and connective tissue proliferation. Patients may experience respiratory disturbances and psychological distress that significantly affect their quality of life when excessive nasal hyperplasia obstructs the external nasal valves. Surgery is the treatment of choice for rhinophyma. However, excessive bleeding, scarring, pigmentation, and high recurrence rates frequently characterize current surgical methods. AIM To evaluate the clinical effectiveness and recurrence rates after treating severe rhinophyma with the five-blade scratcher. METHODS This study retrospectively analyzed the clinical records of 28 patients with severe rhinophyma rosacea. The Global Flushing Severity Score (GFSS), Clinician Erythema Assessment (CEA), Rhinophyma Severity Index (RHISI), Glasgow Benefit Inventory (GBI), and satisfaction scores were used to assess the recovery of patients at 6 months and 5 years, with the recurrence rate calculated at 5 years postoperatively. In addition, the levels of pro-inflammatory factors (TNF-α, IL-1β, and IL-6) in the serum of patients before and after surgery were detected by ELISA. RESULTS The GFSS, CEA, and RHISI scores at 6 months and 5 years postoperatively were significantly lower than those preoperatively (P < 0.001 for both periods). Five-blade scratcher treatment greatly benefits patients as demonstrated by the GBI and patient satisfaction. A small number of patients (7/28, 25%) reported recurrence after surgical treatment for rhinophyma in our department that was not more serious than before treatment. The expression of pro-inflammatory factors (TNF-α, IL-1β, and IL-6) in the patient's serum was significantly reduced after surgery of five-blade scratcher. CONCLUSION The five-blade scratcher treatment demonstrates notable advantages, including simplicity, safety, efficacy, and cost-effectiveness, coupled with reduced bleeding, minimized scarring, lower recurrence rates, reduced the level of pro-inflammatory factors and improved patient satisfaction. Consequently, this therapeutic modality exhibits a viable option for individuals afflicted with severe rhinophyma.
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Affiliation(s)
- Yu-Ping Zheng
- Department of Dermatology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Xu-Feng He
- Department of Dermatology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Yan-Feng Zhang
- Department of Dermatology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Lan-Xin Geng
- Department of Dermatology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Hui-Min Zhang
- Department of Dermatology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Hua Wan
- Department of Galactophore, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Xiang He
- Department of Dermatology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
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Geng RSQ, Bourkas AN, Sibbald RG, Sibbald C. Biomarkers in rosacea: A systematic review. J Eur Acad Dermatol Venereol 2024; 38:1048-1057. [PMID: 38078369 DOI: 10.1111/jdv.19732] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2023] [Accepted: 11/14/2023] [Indexed: 05/26/2024]
Abstract
Rosacea is a chronic and psychologically ladened disease affecting 1%-3% of people worldwide. The identification and validation of biomarkers in rosacea patients has the potential to improve disease progression, support diagnosis, provide objective measures for clinical trials and aid in management. The objective of this review is to systematically identify all rosacea biomarkers, categorize them by type and identify trends to improve disease expression. Eligibility criteria for this review (PROSPERO CRD42023397510) include randomized controlled trials, case-control studies, cohort studies and other observational studies. No restrictions were placed on patient demographics (age, sex, ethnicity) or language of publication until February 2023. Quality of studies was assessed using the National Institute of Health quality assessment tool. The literature search was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. A total of 805 unique articles were screened based on the applied inclusion and exclusion criteria. After the articles were screened based on title/abstract and full-text, a total of 38 studies were included, reporting on a total of 119 unique biomarkers. The results of this review and current rosacea pathogenic mechanisms provide the greatest support for the innate cathelicidin and inflammasome, Th1 and Th17 pathways. The most commonly reported biomarkers include IL-1β, TNF-α, IL-37, IFN-γ and MMP-9. Biomarkers identified in this study support current theories of rosacea pathogenesis and provide direction for research to further our knowledge. However, more research is needed to identify biomarkers panels that can provide diagnostic utility. This may be difficult due to the heterogeneity of the disease and potential differences between rosacea subtypes.
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Affiliation(s)
- R S Q Geng
- Temerty School of Medicine, University of Toronto, Toronto, Ontario, Canada
| | - A N Bourkas
- School of Medicine, Queen's University, Kingston, Ontario, Canada
| | - R G Sibbald
- Dalla Lana School of Public Health & Division of Dermatology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada
| | - C Sibbald
- Division of Pediatric Dermatology, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada
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Henzi BC, Schmidt S, Nagy S, Rubino-Nacht D, Schaedelin S, Putananickal N, Stimpson G, Amthor H, Childs AM, Deconinck N, de Groot I, Horrocks I, Houwen-van Opstal S, Laugel V, Lopez Lobato M, Madruga Garrido M, Nascimento Osorio A, Schara-Schmidt U, Spinty S, von Moers A, Lawrence F, Hafner P, Dorchies OM, Fischer D. Safety and efficacy of tamoxifen in boys with Duchenne muscular dystrophy (TAMDMD): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Neurol 2023; 22:890-899. [PMID: 37739572 DOI: 10.1016/s1474-4422(23)00285-5] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2023] [Revised: 06/28/2023] [Accepted: 07/20/2023] [Indexed: 09/24/2023]
Abstract
BACKGROUND Drug repurposing could provide novel treatment options for Duchenne muscular dystrophy. Because tamoxifen-an oestrogen receptor regulator-reduced signs of muscular pathology in a Duchenne muscular dystrophy mouse model, we aimed to assess the safety and efficacy of tamoxifen in humans as an adjunct to corticosteroid therapy over a period of 48 weeks. METHODS We did a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial at 12 study centres in seven European countries. We enrolled ambulant boys aged 6·5-12·0 years with a genetically confirmed diagnosis of Duchenne muscular dystrophy and who were on stable corticosteroid treatment for more than 6 months. Exclusion criteria included ophthalmological disorders, including cataracts, and haematological disorders. We randomly assigned (1:1) participants using an online randomisation tool to either 20 mg tamoxifen orally per day or matched placebo, stratified by centre and corticosteroid intake. Participants, caregivers, and clinical investigators were masked to treatment assignments. Tamoxifen was taken in addition to standard care with corticosteroids, and participants attended study visits for examinations every 12 weeks. The primary efficacy outcome was the change from baseline to week 48 in scores on the D1 domain of the Motor Function Measure in the intention-to-treat population (defined as all patients who fulfilled the inclusion criteria and began treatment). This study is registered with ClinicalTrials.gov (NCT03354039) and is completed. FINDINGS Between May 24, 2018, and Oct 14, 2020, 95 boys were screened for inclusion, and 82 met inclusion criteria and were initially enrolled into the study. Three boys were excluded after initial screening due to cataract diagnosis or revoked consent directly after screening, but before randomisation. A further boy assigned to the placebo group did not begin treatment. Therefore, 40 individuals assigned tamoxifen and 38 allocated placebo were included in the intention-to-treat population. The primary efficacy outcome did not differ significantly between tamoxifen (-3·05%, 95% CI -7·02 to 0·91) and placebo (-6·15%, -9·19 to -3·11; 2·90% difference, -3·02 to 8·82, p=0·33). Severe adverse events occurred in two participants: one participant who received tamoxifen had a fall, and one who received placebo suffered a panic attack. No deaths or life-threatening serious adverse events occurred. Viral infections were the most common adverse events. INTERPRETATION Tamoxifen was safe and well tolerated, but no difference between groups was reported for the primary efficacy endpoint. Slower disease progression, defined by loss of motor function over time, was indicated in the tamoxifen group compared with the placebo group, but differences in outcome measures were neither clinically nor statistically significant. Currently, we cannot recommend the use of tamoxifen in daily clinical practice as a treatment option for boys with Duchenne muscular dystrophy due to insufficient clinical evidence. FUNDING Thomi Hopf Foundation, ERA-Net, Swiss National Science Foundation, Duchenne UK, Joining Jack, Duchenne Parent Project, Duchenne Parent Project Spain, Fondation Suisse de Recherche sur les Maladies Musculaires, Association Monegasque contre les Myopathies.
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Affiliation(s)
- Bettina C Henzi
- Division of Neuropediatrics and Developmental Medicine, University Children's Hospital Basel, University of Basel, Basel, Switzerland; Department of Neuropediatrics and Muscle Disorders, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - Simone Schmidt
- Division of Neuropediatrics and Developmental Medicine, University Children's Hospital Basel, University of Basel, Basel, Switzerland
| | - Sara Nagy
- Department of Neurology, University Hospital Basel, University of Basel, Basel, Switzerland
| | - Daniela Rubino-Nacht
- Division of Neuropediatrics and Developmental Medicine, University Children's Hospital Basel, University of Basel, Basel, Switzerland
| | - Sabine Schaedelin
- Department of Clinical Research, University of Basel and University Hospital Basel, Basel, Switzerland
| | - Niveditha Putananickal
- Division of Neuropediatrics and Developmental Medicine, University Children's Hospital Basel, University of Basel, Basel, Switzerland
| | - Georgia Stimpson
- Developmental Neuroscience Research and Teaching Department, Faculty of Population Health Sciences, Dubowitz Neuromuscular Centre, UCL Great Ormond Street Institute of Child Health, London, UK
| | - Helge Amthor
- Service de Neurologie et Réanimation Pédiatriques, APHP Paris Saclay, Hôpital Raymond Poincaré, Garches, France
| | | | - Nicolas Deconinck
- Department of Paediatric Neurology and Neuromuscular Reference Center, Hôpital Universitaire des Enfants Reine Fabiola, Université Libre de Bruxelles, Brussels, Belgium
| | - Imelda de Groot
- Department of Rehabilitation, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, Netherlands
| | | | - Saskia Houwen-van Opstal
- Department of Rehabilitation, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, Netherlands
| | - Vincent Laugel
- Department of Pediatric Neurology, Strasbourg University Hospital, Strasbourg, France
| | - Mercedes Lopez Lobato
- Sección de Neurología Pediátrica, Hospital Universitario Virgen del Rocío, Seville, Spain
| | - Marcos Madruga Garrido
- Sección de Neurología Pediátrica, Hospital Universitario Virgen del Rocío, Seville, Spain
| | - Andrés Nascimento Osorio
- Neuromuscular Unit, Department of Neurology, Hospital Sant Joan de Déu and Center for Biomedical Research Network on Rare Diseases, ISCIII, Barcelona, Spain
| | - Ulrike Schara-Schmidt
- Department of Pediatric Neurology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
| | | | - Arpad von Moers
- Department of Pediatrics, DRK Kliniken Berlin Westend, Berlin, Germany
| | | | - Patricia Hafner
- Division of Neuropediatrics and Developmental Medicine, University Children's Hospital Basel, University of Basel, Basel, Switzerland
| | - Olivier M Dorchies
- School of Pharmaceutical Sciences and Institute of Pharmaceutical Sciences of Western Switzerland, University of Geneva, Geneva, Switzerland
| | - Dirk Fischer
- Division of Neuropediatrics and Developmental Medicine, University Children's Hospital Basel, University of Basel, Basel, Switzerland.
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Blum KM, Mirhaidari GJM, Zbinden JC, Breuer C, Barker JC. Tamoxifen reduces silicone implant capsule formation in a mouse model. FASEB Bioadv 2022; 4:638-647. [PMID: 36238364 PMCID: PMC9536088 DOI: 10.1096/fba.2022-00036] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2022] [Revised: 05/19/2022] [Accepted: 06/08/2022] [Indexed: 11/17/2022] Open
Abstract
Capsular contracture as a result of the foreign body response (FBR) is a common issue after implant-based breast reconstruction, affecting up to 20% of patients. New evidence suggests that tamoxifen may mitigate the FBR. C57BL/6 female mice were treated with daily tamoxifen or control injections and implanted with bilateral silicone implants in the submammary glandular plane. Implants were removed en bloc after 2 weeks and the implant capsules were evaluated histologically. Tamoxifen treatment decreased capsule thickness, decreased the number of αSMA+ cells (477 ± 156 cells/mm control vs 295 ± 121 cells/mm tamoxifen, p = 0.005 unpaired t test), and decreased CD31+ cells (173.9 ± 96.1 cells/mm2 control vs 106.3 ± 51.8 cells/mm2 tamoxifen, p = 0.043 unpaired t test). There were similar amounts of pro- and anti-inflammatory macrophages (iNOS 336.1 ± 226.3 cells/mm control vs 290.6 ± 104.2 cells/mm tamoxifen, p > 0.999 Mann-Whitney test and CD163 136.6 ± 76.4 cells/mm control vs 94.1 ± 45.9 cells/mm tamoxifen, p = 0.108 unpaired t test). Tamoxifen treatment in the mouse silicone breast implant model decreased capsule formation through modulation of myofibroblasts, neovascularization, and collagen deposition. Tamoxifen may be useful for reducing or preventing capsule formation in clinical breast implantations.
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Affiliation(s)
- Kevin M. Blum
- Center for Regenerative Medicine, The Abigail Wexner Research InstituteNationwide Children's HospitalColumbusOhioUSA
- Department of Biomedical EngineeringThe Ohio State UniversityColumbusOhioUSA
| | - Gabriel J. M. Mirhaidari
- Center for Regenerative Medicine, The Abigail Wexner Research InstituteNationwide Children's HospitalColumbusOhioUSA
- Biological Sciences Graduate ProgramThe Ohio State UniversityColumbusOhioUSA
| | - Jacob C. Zbinden
- Center for Regenerative Medicine, The Abigail Wexner Research InstituteNationwide Children's HospitalColumbusOhioUSA
- Department of Biomedical EngineeringThe Ohio State UniversityColumbusOhioUSA
| | - Christopher K. Breuer
- Center for Regenerative Medicine, The Abigail Wexner Research InstituteNationwide Children's HospitalColumbusOhioUSA
| | - Jenny C. Barker
- Center for Regenerative Medicine, The Abigail Wexner Research InstituteNationwide Children's HospitalColumbusOhioUSA
- Department of Plastic and Reconstructive Surgery, Wexner Medical CenterThe Ohio State UniversityColumbusOhioUSA
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Tamoxifen Prevents Peritendinous Adhesions: A Preliminary Report. BIOMED RESEARCH INTERNATIONAL 2022; 2022:4250771. [PMID: 36177054 PMCID: PMC9514950 DOI: 10.1155/2022/4250771] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/12/2022] [Revised: 08/16/2022] [Accepted: 08/24/2022] [Indexed: 11/17/2022]
Abstract
Background Scarless healing comprises the ultimate goal after an injury. Since tendon healing results in a fibrotic scar, an injured tendon can never regain the mechanical potential and strength of its uninjured form. A wide variety of studies focus on the tendon healing with an absent or minimal peritendinous adhesions. However, no simple method has managed it at all. Possible complex actions and peritendinous environmental events take place during the tendon healing process. Tamoxifen (TAM), besides its breast cancer-related usage, is a potent antifibrotic drug. Here, we aimed to reduce the peritendinous adhesion with TAM administration. Methods Achilles tendons of 44 Wistar albino rats were randomly distributed in 4 groups. In group 1, bilateral lower extremities were used as control and sham. Groups 2 and 3 were comprised of low-dose (1 mg/kg) and high-dose (40 mg/kg) systemic administration of TAM, respectively. Group 4 included local administration (1 mg/kg) of TAM. Biomechanical, macroscopical, and histopathological analyses were done and compared statistically. Biomechanically, the maximum force that led to tendon rupture was determined, and tensile force data were recorded via tensile testing device. Macroscopical and histopathological analysis were composed of the quantity, quality, and grade of peritendinous adhesions. Results Macroscopic and histopathologic findings revealed that groups 2 and 3 had a variety of values ranging between slight to severe adhesions. In group 2, almost half of the animals had moderate adhesions, whereas in group 3, the majority of the animals had moderate adhesions. There were no animals with moderate or severe adhesions in group 4. Statistically significant values were calculated between sham and control groups. Biomechanically, group 2 showed the most significant result. The tendons in group 2 had the highest stiffness when maximal force was applied to rupture the tendons. Henceforth, all these consequences were proven statistically. Conclusion We achieved less peritendinous adhesion with the local administration of TAM when compared to systemic administration of TAM. A better understanding of the peritendinous environmental process will reveal to develop new therapies in the prevention of peritendinous adhesions.
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Rhinophyma: Taking Care of the “WC Fields” Nose. CURRENT OTORHINOLARYNGOLOGY REPORTS 2022. [DOI: 10.1007/s40136-022-00409-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/17/2022]
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Blum KM, Roby LC, Zbinden JC, Chang YC, Mirhaidari GJM, Reinhardt JW, Yi T, Barker JC, Breuer CK. Sex and Tamoxifen confound murine experimental studies in cardiovascular tissue engineering. Sci Rep 2021; 11:8037. [PMID: 33850181 PMCID: PMC8044102 DOI: 10.1038/s41598-021-87006-3] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2020] [Accepted: 02/25/2021] [Indexed: 02/01/2023] Open
Abstract
Tissue engineered vascular grafts hold promise for the creation of functional blood vessels from biodegradable scaffolds. Because the precise mechanisms regulating this process are still under investigation, inducible genetic mouse models are an important and widely used research tool. However, here we describe the importance of challenging the baseline assumption that tamoxifen is inert when used as a small molecule inducer in the context of cardiovascular tissue engineering. Employing a standard inferior vena cava vascular interposition graft model in C57BL/6 mice, we discovered differences in the immunologic response between control and tamoxifen-treated animals, including occlusion rate, macrophage infiltration and phenotype, the extent of foreign body giant cell development, and collagen deposition. Further, differences were noted between untreated males and females. Our findings demonstrate that the host-response to materials commonly used in cardiovascular tissue engineering is sex-specific and critically impacted by exposure to tamoxifen, necessitating careful model selection and interpretation of results.
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Affiliation(s)
- Kevin M Blum
- Center for Regenerative Medicine, The Abigail Wexner Research Institute, Nationwide Children's Hospital, Columbus, USA
- Department of Biomedical Engineering, The Ohio State University, Columbus, USA
| | - Lauren C Roby
- Center for Regenerative Medicine, The Abigail Wexner Research Institute, Nationwide Children's Hospital, Columbus, USA
- College of Medicine, The Ohio State University, Columbus, USA
| | - Jacob C Zbinden
- Center for Regenerative Medicine, The Abigail Wexner Research Institute, Nationwide Children's Hospital, Columbus, USA
- Department of Biomedical Engineering, The Ohio State University, Columbus, USA
| | - Yu-Chun Chang
- Center for Regenerative Medicine, The Abigail Wexner Research Institute, Nationwide Children's Hospital, Columbus, USA
- Biomedical Sciences Graduate Program, College of Medicine, The Ohio State University, Columbus, USA
| | - Gabriel J M Mirhaidari
- Center for Regenerative Medicine, The Abigail Wexner Research Institute, Nationwide Children's Hospital, Columbus, USA
- Biomedical Sciences Graduate Program, College of Medicine, The Ohio State University, Columbus, USA
| | - James W Reinhardt
- Center for Regenerative Medicine, The Abigail Wexner Research Institute, Nationwide Children's Hospital, Columbus, USA
| | - Tai Yi
- Center for Regenerative Medicine, The Abigail Wexner Research Institute, Nationwide Children's Hospital, Columbus, USA
| | - Jenny C Barker
- Center for Regenerative Medicine, The Abigail Wexner Research Institute, Nationwide Children's Hospital, Columbus, USA
- Department of Plastic and Reconstructive Surgery, The Ohio State University, Columbus, USA
| | - Christopher K Breuer
- Center for Regenerative Medicine, The Abigail Wexner Research Institute, Nationwide Children's Hospital, Columbus, USA.
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Abstract
Rhinophyma is a rare subtype of rosacea, which is a thickening of the skin in the nasal area due to an overgrowth of the sebaceous glands and the underlying connective tissue. The exact pathogenesis of rhinophyma is unknown, but potential factors include a combination of neurovascular disorders, innate immune responses, and the presence of microorganisms. The article presents current data on the treatment of rosacea, in particular, rhinophyma. A clinical case of a 67-year-old patient with a combination of papulo-pustular subtype of rosacea and rhinophyma is presented. The high effectiveness of the therapy with systemic isotretinoin was demonstrated.
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Chauhan R, Loewenstein SN, Hassanein AH. Rhinophyma: Prevalence, Severity, Impact and Management. Clin Cosmet Investig Dermatol 2020; 13:537-551. [PMID: 32848439 PMCID: PMC7429105 DOI: 10.2147/ccid.s201290] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2020] [Accepted: 07/21/2020] [Indexed: 12/29/2022]
Abstract
Rhinophyma is an advanced stage of rosacea affecting the nasal soft tissues and resulting in disruption of the nasal architecture, airway obstruction, and disfigurement of the nasal aesthetic units. Rhinophyma presents with hypertrophy of the nasal soft tissues, erythema, telangiectasias, nodules, and lobules with a bulbous appearance. Significant psychosocial morbidity is associated with the disease. Understanding of this disease has improved and multiple treatment options exist. The article is a review of the literature to evaluate the pathophysiology, clinical presentation, and epidemiology of keywords “rhinophyma” and “rosacea” using an OVID Medline and PubMed search along with a systematic review of outcomes pertaining to treatment of rhinophyma with laser therapy, scalpel excision, and the subunit method using an OVID Medline search. The subunit method has the highest complication and revision rates followed by carbon dioxide laser therapy. Outcomes between carbon dioxide laser and scalpel therapy and electrocautery are equivalent. Scalpel excision is a more cost-effective treatment modality with less post-operative complications; however, it risks poor hemostasis intraoperatively. Patient satisfaction is common post-therapy regardless of the treatment method. Over 89% of patients would recommend undergoing treatment for rhinophyma irrespective of treatment type. Treatment options vary, and choice of treatment can be dependent on practitioner and patients’ treatment goals.
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Affiliation(s)
- Ruvi Chauhan
- Indiana University School of Medicine, Department of Surgery, Division of Plastic Surgery, Indianapolis, IN, USA
| | - Scott N Loewenstein
- Indiana University School of Medicine, Department of Surgery, Division of Plastic Surgery, Indianapolis, IN, USA
| | - Aladdin H Hassanein
- Indiana University School of Medicine, Department of Surgery, Division of Plastic Surgery, Indianapolis, IN, USA
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Microdebrider-Assisted Rhinophyma Excision. Case Rep Otolaryngol 2019; 2019:4915416. [PMID: 31885991 PMCID: PMC6925738 DOI: 10.1155/2019/4915416] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2019] [Accepted: 11/02/2019] [Indexed: 11/30/2022] Open
Abstract
Rhinophyma represents a progressive deformity of the nose which leads to cosmetic disfigurement and has a significant impact on the patient's quality of life. This pathological entity originates from hyperplasia of sebaceous gland tissue, connective tissue, and vessels of the nose and is associated with rosacea and more specifically, stage III rosacea. Surgical treatment is the method of choice. We present five cases of rhinophyma that we treated with microdebrider-assisted excision. The procedure was divided in two main steps: scalpel excision of the main bulk of the rhinophyma and then further contouring with the microdebrider. All patients had weekly follow-up for the first four weeks, and then three-monthly. All patients had uneventful recovery and satisfactory cosmetic outcomes. No postoperative infections or other complications were reported in our case series. The use of the microdebrider reduces the operating time, preserves the islands of skin regeneration, and allows finer manipulations than the standard scalpel techniques. Microdebrider-assisted rhinophyma excision is a safe approach, with good aesthetic results. Larger series of patients need to be examined in order to establish the value of the method.
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12
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Gayi E, Neff LA, Massana Muñoz X, Ismail HM, Sierra M, Mercier T, Décosterd LA, Laporte J, Cowling BS, Dorchies OM, Scapozza L. Tamoxifen prolongs survival and alleviates symptoms in mice with fatal X-linked myotubular myopathy. Nat Commun 2018; 9:4848. [PMID: 30451843 PMCID: PMC6243013 DOI: 10.1038/s41467-018-07058-4] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2018] [Accepted: 10/12/2018] [Indexed: 11/08/2022] Open
Abstract
X-linked myotubular myopathy (XLMTM, also known as XLCNM) is a severe congenital muscular disorder due to mutations in the myotubularin gene, MTM1. It is characterized by generalized hypotonia, leading to neonatal death of most patients. No specific treatment exists. Here, we show that tamoxifen, a well-known drug used against breast cancer, rescues the phenotype of Mtm1-deficient mice. Tamoxifen increases lifespan several-fold while improving overall motor function and preventing disease progression including lower limb paralysis. Tamoxifen corrects functional, histological and molecular hallmarks of XLMTM, with improved force output, myonuclei positioning, myofibrillar structure, triad number, and excitation-contraction coupling. Tamoxifen normalizes the expression level of the XLMTM disease modifiers DNM2 and PI3KC2B, likely contributing to the phenotypic rescue. Our findings demonstrate that tamoxifen is a promising candidate for clinical evaluation in XLMTM patients.
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MESH Headings
- Animals
- Class II Phosphatidylinositol 3-Kinases/genetics
- Class II Phosphatidylinositol 3-Kinases/metabolism
- Disease Models, Animal
- Disease Progression
- Dynamin II/genetics
- Dynamin II/metabolism
- Electric Stimulation
- Excitation Contraction Coupling/drug effects
- Female
- Gene Expression/drug effects
- Genes, Lethal
- Humans
- Longevity/drug effects
- Male
- Mice
- Mice, Knockout
- Motor Activity/drug effects
- Muscle, Skeletal/drug effects
- Muscle, Skeletal/metabolism
- Muscle, Skeletal/pathology
- Myofibrils/drug effects
- Myofibrils/metabolism
- Myofibrils/ultrastructure
- Myopathies, Structural, Congenital/drug therapy
- Myopathies, Structural, Congenital/genetics
- Myopathies, Structural, Congenital/metabolism
- Myopathies, Structural, Congenital/pathology
- Protective Agents/pharmacology
- Protein Tyrosine Phosphatases, Non-Receptor/deficiency
- Protein Tyrosine Phosphatases, Non-Receptor/genetics
- Tamoxifen/pharmacology
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Affiliation(s)
- Elinam Gayi
- Pharmaceutical Biochemistry Group, School of Pharmaceutical Sciences, University of Lausanne, University of Geneva, CMU 5-6, Rue Michel-Servet 1, Geneva, 1211, Switzerland
| | - Laurence A Neff
- Pharmaceutical Biochemistry Group, School of Pharmaceutical Sciences, University of Lausanne, University of Geneva, CMU 5-6, Rue Michel-Servet 1, Geneva, 1211, Switzerland
| | - Xènia Massana Muñoz
- Department of Translational Medicine and Neurogenetics, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Illkirch, 67404, France
- Centre National de la Recherche Scientifique (CNRS), UMR7104, Illkirch, 67404, France
- Institut National de la Santé et de la Recherche Médicale (INSERM), U1258, Illkirch, 67404, France
- Université de Strasbourg, Illkirch, 67404, France
| | - Hesham M Ismail
- Pharmaceutical Biochemistry Group, School of Pharmaceutical Sciences, University of Lausanne, University of Geneva, CMU 5-6, Rue Michel-Servet 1, Geneva, 1211, Switzerland
| | - Marta Sierra
- Pharmaceutical Biochemistry Group, School of Pharmaceutical Sciences, University of Lausanne, University of Geneva, CMU 5-6, Rue Michel-Servet 1, Geneva, 1211, Switzerland
| | - Thomas Mercier
- Division and Laboratory of Clinical Pharmacology, Service of Biomedicine, Department of Laboratories, Lausanne University Hospital, Lausanne, 1011, Switzerland
| | - Laurent A Décosterd
- Division and Laboratory of Clinical Pharmacology, Service of Biomedicine, Department of Laboratories, Lausanne University Hospital, Lausanne, 1011, Switzerland
| | - Jocelyn Laporte
- Department of Translational Medicine and Neurogenetics, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Illkirch, 67404, France
- Centre National de la Recherche Scientifique (CNRS), UMR7104, Illkirch, 67404, France
- Institut National de la Santé et de la Recherche Médicale (INSERM), U1258, Illkirch, 67404, France
- Université de Strasbourg, Illkirch, 67404, France
| | - Belinda S Cowling
- Department of Translational Medicine and Neurogenetics, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Illkirch, 67404, France
- Centre National de la Recherche Scientifique (CNRS), UMR7104, Illkirch, 67404, France
- Institut National de la Santé et de la Recherche Médicale (INSERM), U1258, Illkirch, 67404, France
- Université de Strasbourg, Illkirch, 67404, France
| | - Olivier M Dorchies
- Pharmaceutical Biochemistry Group, School of Pharmaceutical Sciences, University of Lausanne, University of Geneva, CMU 5-6, Rue Michel-Servet 1, Geneva, 1211, Switzerland.
| | - Leonardo Scapozza
- Pharmaceutical Biochemistry Group, School of Pharmaceutical Sciences, University of Lausanne, University of Geneva, CMU 5-6, Rue Michel-Servet 1, Geneva, 1211, Switzerland.
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Abstract
BACKGROUND Rhinophyma is the overgrowth of sebaceous glands in nasal tissue and its etiology unclear. Without treatment, rhinophyma can be progressive and cause concern both with respect to function and cosmesis. OBJECTIVE The objective of this work is to describe treatment options for rhinophyma and their respective risks and benefits. MATERIALS AND METHODS A PubMed search was performed to include the terms "rhinophyma" and "treatment." RESULTS Numerous physically destructive modalities exist for treatment of rhinophyma, falling primarily into 3 categories: mechanical destruction, directed electrical energy/radiofrequency, and directed laser energy. CONCLUSION There are multiple treatment modalities available to dermatologists for the treatment of rhinophyma. To the best of our knowledge, there are no randomized, prospective, control studies for any treatment, which makes it difficult to recommend a single treatment over another. Nonetheless, it is important to recognize that scarring and hypopigmentation most often occur on or near the nasal ala. Moreover, risks may increase if tissue destruction extends to the papillary dermis or pilosebaceous units are ablated.
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Cho E, Zhang Y, Pruznak A, Kim HM. Effect of tamoxifen on fatty degeneration and atrophy of rotator cuff muscles in chronic rotator cuff tear: An animal model study. J Orthop Res 2015; 33:1846-53. [PMID: 26121952 DOI: 10.1002/jor.22964] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/09/2015] [Accepted: 06/03/2015] [Indexed: 02/04/2023]
Abstract
Fatty degeneration of the rotator cuff muscles is an irreversible change resulting from chronic rotator cuff tear and is associated with poor clinical outcomes following rotator cuff repair. We evaluated the effect of Tamoxifen, a competitive estrogen receptor inhibitor, on fatty degeneration using a mouse model for chronic rotator cuff tear. Sixteen adult mice were divided into two diet groups (Tamoxifen vs. Regular) and subjected to surgical creation of a large rotator cuff tear and suprascapular nerve transection in their left shoulder with the right shoulder serving as a control. The rotator cuff muscles were harvested at 16 weeks and subjected to histology and RT-PCR for adipogenic and myogenic markers. Histology showed substantially decreased atrophy and endomysial inflammation in Tamoxifen group, but no significant differences in the amount of intramuscular adipocytes and lipid droplets compared to the Regular group. With RT-PCR, the operated shoulders showed significant upregulation of myogenin and PPAR-γ, and downregulation of myostatin compared to the nonsurgical shoulder. No significant differences of gene expression were found between the two diet groups. Our study demonstrated that tamoxifen diet leads to decreased muscle atrophy and inflammatory changes following chronic rotator cuff tear, but has no apparent effect on adipogenesis.
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Affiliation(s)
- Edward Cho
- Department of Orthopaedics and Rehabilitation, Penn State College of Medicine, Hershey, Pennsylvania
| | - Yue Zhang
- Department of Orthopaedics and Rehabilitation, Penn State College of Medicine, Hershey, Pennsylvania
| | - Anne Pruznak
- Cellular and Molecular Physiology, Penn State College of Medicine, Hershey, Pennsylvania
| | - H Mike Kim
- Department of Orthopaedics and Rehabilitation, Penn State College of Medicine, Hershey, Pennsylvania
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15
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16
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Tamoxifen citrate: a glimmer of hope for silicosis. J Surg Res 2015; 193:429-34. [DOI: 10.1016/j.jss.2014.08.013] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2014] [Revised: 08/06/2014] [Accepted: 08/08/2014] [Indexed: 11/22/2022]
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Dorchies OM, Reutenauer-Patte J, Dahmane E, Ismail HM, Petermann O, Patthey- Vuadens O, Comyn SA, Gayi E, Piacenza T, Handa RJ, Décosterd LA, Ruegg UT. The anticancer drug tamoxifen counteracts the pathology in a mouse model of duchenne muscular dystrophy. THE AMERICAN JOURNAL OF PATHOLOGY 2013; 182:485-504. [PMID: 23332367 DOI: 10.1016/j.ajpath.2012.10.018] [Citation(s) in RCA: 73] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/18/2012] [Revised: 09/17/2012] [Accepted: 10/07/2012] [Indexed: 12/18/2022]
Abstract
Duchenne muscular dystrophy (DMD) is a severe disorder characterized by progressive muscle wasting,respiratory and cardiac impairments, and premature death. No treatment exists so far, and the identification of active substances to fight DMD is urgently needed. We found that tamoxifen, a drug used to treat estrogen-dependent breast cancer, caused remarkable improvements of muscle force and of diaphragm and cardiac structure in the mdx(5Cv) mouse model of DMD. Oral tamoxifen treatment from 3 weeks of age for 15 months at a dose of 10 mg/kg/day stabilized myofiber membranes, normalized whole body force, and increased force production and resistance to repeated contractions of the triceps muscle above normal values. Tamoxifen improved the structure of leg muscles and diminished cardiac fibrosis by~ 50%. Tamoxifen also reduced fibrosis in the diaphragm, while increasing its thickness,myofiber count, and myofiber diameter, thereby augmenting by 72% the amount of contractile tissue available for respiratory function. Tamoxifen conferred a markedly slower phenotype to the muscles.Tamoxifen and its metabolites were present in nanomolar concentrations in plasma and muscles,suggesting signaling through high-affinity targets. Interestingly, the estrogen receptors ERa and ERb were several times more abundant in dystrophic than in normal muscles, and tamoxifen normalized the relative abundance of ERb isoforms. Our findings suggest that tamoxifen might be a useful therapy for DMD.
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MESH Headings
- Animals
- Antineoplastic Agents/pharmacology
- Antineoplastic Agents/therapeutic use
- Behavior, Animal/drug effects
- Biomarkers/metabolism
- Biomechanical Phenomena/drug effects
- Body Weight/drug effects
- Creatine Kinase/blood
- Diaphragm/pathology
- Diaphragm/physiopathology
- Disease Models, Animal
- Feeding Behavior/drug effects
- Fibrosis
- Mice
- Muscle Contraction/drug effects
- Muscle Fibers, Skeletal/drug effects
- Muscle Fibers, Skeletal/pathology
- Muscular Dystrophy, Animal/blood
- Muscular Dystrophy, Animal/drug therapy
- Muscular Dystrophy, Animal/pathology
- Muscular Dystrophy, Animal/physiopathology
- Muscular Dystrophy, Duchenne/blood
- Muscular Dystrophy, Duchenne/drug therapy
- Muscular Dystrophy, Duchenne/pathology
- Muscular Dystrophy, Duchenne/physiopathology
- Myocardium/pathology
- Organ Size/drug effects
- Receptors, Estrogen/metabolism
- Tamoxifen/blood
- Tamoxifen/pharmacology
- Tamoxifen/therapeutic use
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Affiliation(s)
- Olivier M Dorchies
- Department of Pharmacology, University of Geneva and University of Lausanne, Geneva, Switzerland.
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Gerber PA, Buhren BA, Steinhoff M, Homey B. Rosacea: The cytokine and chemokine network. J Investig Dermatol Symp Proc 2012; 15:40-7. [PMID: 22076326 DOI: 10.1038/jidsymp.2011.9] [Citation(s) in RCA: 111] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Rosacea is one of the most common dermatoses of adults. Recent studies have improved our understanding of the pathophysiology of rosacea. Current concepts suggest that known clinical trigger factors of rosacea such as UV radiation, heat, cold, stress, spicy food, and microbes modulate Toll-like receptor signaling, induce reactive oxygen species, as well as enhance antimicrobial peptide and neuropeptide production. Downstream of these events cytokines and chemokines orchestrate an inflammatory response that leads to the recruitment and activation of distinct leukocyte subsets and induces the characteristic histopathological features of rosacea. Here we summarize the current knowledge of the cytokine and chemokine network in rosacea and propose pathways that may be of therapeutic interest.
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Affiliation(s)
- Peter Arne Gerber
- Department of Dermatology, University Hospital Düsseldorf, Düsseldorf, Germany
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19
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Liu Y, Xiao Z, Yang D, Ren L, Liu G, Yang L. Effects of the cyclin-dependent kinase 10 (CDK10) on the tamoxifen sensitivity of keloid samples. Molecules 2012; 17:1307-18. [PMID: 22298115 PMCID: PMC6268744 DOI: 10.3390/molecules17021307] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2011] [Revised: 01/14/2012] [Accepted: 01/17/2012] [Indexed: 01/21/2023] Open
Abstract
Cyclin-dependent kinase 10 (CDK10) is a cell cycle regulating protein kinase, which has just been discriminated in recent years. In this paper, mRNA and protein expression of CDK10 were first investigated by a comparative study between 23 human keloid tissue samples and their adjacent normal skin. To further address its potential as a therapeutic target in the treatment of keloid, a plasmid expressing the CDK10 gene was transfected into keloid fibroblast. The effects on tamoxifen-induced apoptosis were then investigated using Western blot assay and flow cytometry. Results showed that there is a generally down-regulated expression of CDK10 in keloid compared to normal skin samples. Transfection with the recombinant CDK10 plasmid significantly decreased the viability of cells and increased the apoptosis rates. Tamoxifen sensitivity in keloid fibroblasts was observed after treatment with the recombinant CDK10 plasmid. The results suggested that CDK10 may play an important role in enhancement of tamoxifen efficiency, and its expression may have a synergistic effect on keloid treatments.
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Affiliation(s)
- Ying Liu
- Department of Plastic and Aesthetic, The Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China.
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20
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Abstract
INTRODUCTION Rhinophyma is a disfiguring hypertrophy of the skin of the tip of the nose. OBJECTIVE To assess the new technique of coblation of rhinophyma. STUDY DESIGN Case series of six patients. RESULTS All patients had a good cosmetic result. Comparison with existing techniques showed advantages due to the lower tissue temperature involved. CONCLUSION Coblation of rhinophyma is an effective treatment with few side effects.
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Encapsulating peritoneal sclerosis: a single-center experience and review of the literature. Int Urol Nephrol 2010; 43:519-26. [PMID: 20924672 DOI: 10.1007/s11255-010-9848-y] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2010] [Accepted: 09/09/2010] [Indexed: 12/18/2022]
Abstract
Encapsulating peritoneal sclerosis (EPS) is a serious and often fatal complication of long-term PD with severe malnutrition and poor prognosis. It causes progressive obstruction and encapsulation of the bowel. This retrospective study reviews our experience and that reviewed in the literature concerning EPS. It refers to a total of 1966 patients treated with chronic PD between 1974 and 2008. Twenty one of them (1.1%) developed EPS, with the incidence increasing with the duration of PD. Mean age of our patients with EPS was 43, ranging from 18 to 71 years, 8 were men and 13 women with a mean body mass index (BMI) of 21.6 kg/m(2). Only one patient had Type II diabetes, 15 patients had glomerular disease, and six of these 15 had an autoimmune disease such as Wegener's granulomatosis and SLE. Thirteen patients developed EPS while on PD, 7 within 2 years after transfer to HD, and only one after renal transplantation. However, 7 patients had a previous renal transplant before returning to PD and subsequently developing EPS. Interestingly, we did not observe more episodes of EPS after transplantation. In the patients who developed EPS, the peritonitis rate over the period of observation was 1/15.6 pt-months and was due to Staphylococcus aureus, coagulase-negative staphylococcus, Pseudomonas and fungi. A history of peritonitis was not a prerequisite for developing EPS, since one patient had no episodes of peritonitis and 4 had just one previous episode. Fifteen patients presented with peritonitis within 4 months before the diagnosis of EPS with particularly virulent micro-organisms such as S. aureus, Candida, Pseudomonas, Corynebacterium, and Peptostreptococcus. Eleven patients were treated with hypertonic dextrose solutions (4.25 g/dl of dextrose) and seven with icodextrin, indirectly suggesting problems with ultrafiltration. Nine of 21 patients were on beta-blockers. The diagnosis of EPS was made either surgically or radiologically with signs of small bowel obstruction in combination with severe malnutrition. Eleven of our patients (52%) had evidence of small bowel obstruction and 14 patients required total parenteral nutrition (TPN). Tamoxifen (10-20 mg daily) was started in 6 patients, 4 of whom are alive and 2 deceased 3 and 5 years after EPS was diagnosed. Of the 12 patients who were not given tamoxifen, 2 are alive and 10 died. No side effects of tamoxifen were reported. Only 7 of our patients (33%) died during the first year after the diagnosis of EPS. Currently, 4 patients are on HD and 3 have had a renal transplant. Six patients of the fourteen who underwent surgery (42.8%) died within the first 6 months after operation and five died after an average of 6.6 years, mostly due to cardiovascular causes, three are still alive. As EPS becomes more prevalent with longer duration of PD, large multicenter prospective studies are needed to establish its incidence and identify risk factors, therapeutic approach, and prognosis.
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Sobottka A, Lehmann P. [Rosacea 2009 : new advances in pathophysiology, clinical staging and therapeutic strategies]. Hautarzt 2010; 60:999-1009. [PMID: 19957073 DOI: 10.1007/s00105-009-1825-y] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
Rosacea is one of the most common dermatoses of adults. In recent years many studies have contributed to a better understanding of the pathophysiology of rosacea. They suggest that an altered innate immune response is involved in the vascular and inflammatory manifestations seen in rosacea. A good understanding of the disease and its special features is necessary for the differential diagnosis of the many clinical subtypes and for a stage- and phase-specific treatment approach. Topical treatments that are widely accepted are metronidazole and azelaic acid; agents under investigation that show promise include permethrin, calcineurin inhibitors and sulfur compounds. For systemic therapy antibiotics (tetracyclines, macrolides) and recently doxycycline in anti-inflammatory rather than anti-microbial dosages are used, as well as isotretinoin in severe cases. Findings such as rhinophyma and telangiectases can be treated using different laser systems or dermabrasion. This article gives an overview regarding rosacea, a challenging condition with multiple therapeutic options.
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Affiliation(s)
- A Sobottka
- Zentrum für Dermatologie, Allergologie und Dermatochirurgie - Kompetenzzentrum Hautkrebs, HELIOS-Klinikum Wuppertal, Heusner Str. 40, 42283, Wuppertal, Deutschland.
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23
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Affiliation(s)
- Steven Guest
- Peritoneal Dialysis Unit, Kaiser Permanente Santa Clara, Santa Clara, and Stanford University School of Medicine, Stanford, California, USA
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24
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Allah KC, Kossoko H, Yéo S, Richard Kadio M, Assi Djè Bi Djè V. [Rhinophyma in a black African male patient]. ACTA ACUST UNITED AC 2009; 110:347-9. [PMID: 19428039 DOI: 10.1016/j.stomax.2009.03.009] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2008] [Revised: 02/20/2009] [Accepted: 03/02/2009] [Indexed: 10/20/2022]
Abstract
UNLABELLED Rhinophyma is an irregular and progressive nasal hypertrophy, due to hyperplasia and fibrosis of the sebaceous glands and surrounding soft tissues. Its etiology is unknown. Its psychosocial, functional, and esthetic consequences may be severe. It is rare in the black African population. We present a case of glandular rhinophyma in a 70-year-old black male patient. OBSERVATION A 70-year-old male patient consulted for nasal tumors. These lesions had appeared 11 years before, after rosacea acnea. The patient had no specific history, no alcohol addiction nor any particular treatment. The nose was voluminous. The tumors were located on the left nostril ala, the tip of the nose, and the tip and right nostril ala junction. The size of the pediculated lesions was variable. They covered most of the nostril opening and upper lip. Pressure forced out whitish, pasty, and fetid sebum. The lesions were an obstacle to nasal ventilation and feeding. This glandular rhinophyma was responsible for a severe social and affective handicap. It was treated by exeresis and simple closure, under local anesthesia. Operative follow-up was uneventful. No sign of relapse was noted at 20 months. The psychosocial, functional, and esthetic results were satisfactory. DISCUSSION The rhinophyma is a rare presentation in the black African or Afro-American population. Three cases have been reported so far.
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Affiliation(s)
- K C Allah
- Service de chirurgie plastique, reconstructrice, esthétique, chirurgie de la main et de brûlologie, CHU de Treichville, 01 BP V3 Abidjan 01, Côte d'Ivoire.
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25
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Guest S. Tamoxifen Therapy for Encapsulating Peritoneal Sclerosis: Mechanism of Action and Update on Clinical Experiences. Perit Dial Int 2009. [DOI: 10.1177/089686080902900304] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Affiliation(s)
- Steven Guest
- Peritoneal Dialysis Unit, Kaiser Permanente, Santa Clara, and Stanford University School of Medicine, Stanford, California, USA
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Stevenson S, Nelson LD, Sharpe DT, Thornton MJ. 17beta-estradiol regulates the secretion of TGF-beta by cultured human dermal fibroblasts. JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION 2008; 19:1097-109. [PMID: 18644234 DOI: 10.1163/156856208784909354] [Citation(s) in RCA: 32] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Estrogen plays an important role in skin homeostasis, as demonstrated by the changes seen in the skin of post-menopausal women, changes reversed by HRT. Estrogen also has a role in wound healing, since estrogen deficiency as occurs post-menopausally and in ovariectomised animals, is associated with a reduced rate of wound healing. Estrogen appears to modulate all phases of wound healing with effects on inflammatory cells, epithelialization, angiogenesis, extracellular matrix deposition and tissue remodelling. This study was designed to investigate the effects of 17beta-estradiol on cultured human dermal fibroblasts using an in vitro wound-healing assay. The end points investigated were cell migration, proliferation, total collagen secretion and active TGF-beta1 secretion. 17beta-estradiol significantly increased the migration and proliferation of cultured dermal fibroblasts following mechanical wounding, although the secretion of total soluble collagen was not altered. An increase in TGF-beta1 was demonstrated by unwounded confluent dermal fibroblast monolayers in response to 17beta-estradiol, but paradoxically, a decrease in the secretion of TGF-beta1 was demonstrated in the mechanically wounded dermal fibroblasts. These results identify human dermal fibroblasts as estrogen target cells and provide further evidence for a role by which estrogen regulates this particular cell type as part of the wound-healing process. However, the paradoxical nature of the effect of estrogen on TGF-beta1 secretion following mechanical wounding suggests that the cellular mechanism of action is complex. A greater understanding of the cell-specific action of estrogen may help to develop therapies that will improve cutaneous wound healing in the future.
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Affiliation(s)
- S Stevenson
- Burns & Plastic Surgery Research Unit, Medical Biosciences, School of Life Sciences, University of Bradford, Richmond Road, Bradford, West Yorkshire, UK
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27
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Franz MG, Steed DL, Robson MC. Optimizing healing of the acute wound by minimizing complications. Curr Probl Surg 2007; 44:691-763. [PMID: 18036992 DOI: 10.1067/j.cpsurg.2007.07.001] [Citation(s) in RCA: 98] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Affiliation(s)
- Michael G Franz
- University of Michigan School of Medicine, Ann Arbor, Michigan, USA
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