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Stem Cell Ophthalmology Treatment Study(SCOTS) for retinal and optic nerve diseases: a case report of improvement in relapsing auto-immune optic neuropathy

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Neural Regeneration Research 2015年第6期10卷 1507-1515页

作者： Jeffrey N.Weiss Steven Levy Susan C.Benes Retina Associates of South Florida MD Stem Cells wilmer Eye institute The Johns Hopkins Hospital

We present the results from a patient with relapsing optic neuropathy treated within the Stem Cell Ophthalmology Treatment Study （SCOTS）. SCOTS is an Institutional Review Board ap- proved clinical trial and has become the largest ophthalmology stem cell study registered at the National institutes of Health to date （*** Identifier NCT 01920867）. SCOTS utilizes autologous bone marrow-derived stem cells （BMSCs） for treatment of retinal and optic nerve diseases. Pre-treatment and post-treatment comprehensive eye exams of a 54 year old female patient were performed both at the Florida Study Center, USA and at The Eye Center of Columbus, USA. As a consequence of a relapsing optic neuritis, the patient＇s previously normal visual acuity decreased to between 20/350 and 20/400 in the right eye and to 20/70 in the left eye. Significant visual field loss developed bilaterally. The patient underwent a right eye vitrectomy with injection of BMSCs into the optic nerve of the right eyeand retrobulbar, subtenon and in- travitreal injection of BMSCs in the left eye. At 15 months after SCOTS treatment, the patient＇s visual acuity had improved to 20/150 in the right eye and 20/20 in the left eye. Bilateral visual fields improved markedly. Both macular thickness and fast retinal nerve fiber layer thickness were maximally improved at 3 and 6 months after SCOTS treatment. The patient also reduced her mycophenylate dose from 1,500 mg per day to 500 mg per day and required no steroid pulse therapy during the 15-month follow up.

关键词： nerve regeneration stem cells optic nerve autoimmune optic neuropathy ophthalmology bone marrow-derived stem cells blindness visual loss Stem Cell Ophthalmology Treatment Study neural regeneration

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Role of endoplasmic reticulum stress in the loss of retinal ganglion cells in diabetic retinopathy

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Neural Regeneration Research 2013年第33期8卷 3148-3158页

作者： Liping Yang Lemeng Wu Dongmei Wang Ying Li Hongliang Dou Mark O.M.Tso Zhizhong Ma Department of Ophthalmology Peking University Third HospitalKey Laboratory of Vision Loss and RestorationMinistry of Education wilmer Eye institute Johns Hopkins University School of Medicine

Endoplasmic reticulum stress is closely involved in the early stage of diabetic retinopathy. In the present study, a streptozotocin-induced diabetic animal model was given an intraperitoneal injection of tauroursodeoxycholic acid. Results from immunofluorescent co-localization experiments showed that both caspase-12 protein and c-Jun N-terminal kinase 1 phosphorylation levels significantly in- creased, which was associated with retinal ganglion cell death in diabetic retinas. The C/ERB ho- mologous protein pathway directly contributed to glial reactivity, and was subsequently responsible for neuronal loss and vascular abnormalities in diabetic retinopathy. Our experimental findings in- dicate that endoplasmic reticulum stress plays an important role in diabetes-induced retinal neu- ronal loss and vascular abnormalities, and that inhibiting the activation of the endoplasmic reticulum stress pathway provides effective protection against diabetic retinopathy.

关键词： neural regeneration peripheral nerve injury endoplasmic reticulum stress diabetic retinopathy injury of retinal ganglion cells M011er cells astrocytes c-Jun N-terminal kinase caspase-12 protein C/ERB homologous protein retinal microcirculation glial fibrillary acidic protein grant-supportedpaper neuroregeneration

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Endothelium-specific gene and stem cell-based therapy for erectile dysfunction

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Asian Journal of Andrology 2008年第1期10卷 14-22页

作者： Travis D. Strong Milena A. Gebska Arthur L. Bumett Hunter C. Champion Trinity J. Bivalacqua The Brady Urological institute Department of Urology Johns Hopkins Hospital Baltimore MD 21287 USA Division of Cardiology Department of Medicine Johns Hopkins Hospital Baltimore MD 21287 USA

Erectile dysfunction （ED） commonly results from endothelial dysfunction of the systemic vasculature. Although phosphodiesterase type 5 （PDE-5） inhibitors are effective at treating most cases of ED, they must be taken routinely and are ineffectual for a meaningful number of men. In recent years gene and stem cell-based therapies targeted at the penile endothelium have been gaining momentum in preclinical studies. These early studies reveal that gene and stem cell-based therapies may be both enduring and efficacious, and may eventually lead to a cure for ED. The following review will highlight our current understanding of endothelial-specific gene and stem cell-based therapies performed to date in a number of experimental animal models.

关键词： erectile dysfunction endothelial-specific gene endothelial dysfunction gene therapy

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眼内晶体植入适应症的变化

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眼科学报 1986年第1期2卷 26-32页

作者： WalterJ.Stark ArloC.Terry A.EdwardMaumenee The wilmer institute johns hopkins hospital U.S.A. The wilmer institute johns hopkins hospital U.S.A. The wilmer institute johns hopkins hospital U.S.A.

白内障是世界上一百多个国家中致盲的重要原因,也是美国第三位的致盲原因。因此,白内障成为一个重要的公共卫生问题。1984年,美国施行了700,000多例白内障手术,而且85%以上同时作了眼内晶体植入。虽则白内障手术高度成功,但黄斑囊样水... 详细信息

白内障是世界上一百多个国家中致盲的重要原因,也是美国第三位的致盲原因。因此,白内障成为一个重要的公共卫生问题。1984年,美国施行了700,000多例白内障手术,而且85%以上同时作了眼内晶体植入。虽则白内障手术高度成功,但黄斑囊样水肿和角膜水肿等并发症仍然是个问题。本报告将指出当前美国眼内晶体植入的方向,并阐述在 wilmer 研究所作的2500多例眼内晶体植入及那些报告给美国食品、药物管理处的病例的结果。

关键词：晶体植入眼内 IOL 适应症

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Hepatorenal syndrome

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World Journal of Gastroenterology 2007年第30期13卷 4046-4055页

作者： Sharon Turban Paul J Thuluvath Mohamed G Atta Department of Medicine Division of Nephrology Johns Hopkins School of Medicine and the Johns Hopkins Hospital Baltimore Maryland United States Department of Medicine Division of Gastroenterology Johns Hopkins School of Medicine and the Johns Hopkins Hospital Baltimore Maryland United States

Hepatorenal syndrome (HRS) is a "functional" and reversible form of renal failure that occurs in patients with advanced chronic liver disease. The distinctive hallmark feature of HRS is the intense renal vasoconstriction caused by interactions between systemic and portal hemodynamics. This results in activation of vasoconstrictors and suppression of vasodilators in the renal circulation. Epidemiology, pathophysiology, as well as current and emerging therapies of HRS are discussed in this review.

关键词： Acute renal failure End stage liver disease Hepatorenal syndrome Transjugular intrahepatic portosysternic shunts Dialysis Liver transplantation

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Surgery for colorectal liver metastases: The evolution of determining prognosis

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World Journal of Gastrointestinal Oncology 2013年第12期5卷 207-221页

作者： Gaya Spolverato Aslam Ejaz Nilo Azad Timothy M Pawlik Department of Surgery The Johns Hopkins Hospital Department of Medical Oncology The Johns Hopkins Hospital

Despite improvements in the multi-modality treatment of colorectal liver metastasis (CRLM), survival after resection remains varied. Determining prognosis after surgical resection has historically been predicated on preoperative clinicopathological factors such as primary tumor stage, carcinoembryonic antigen levels, number of liver metastases, presence of extrahepatic disease, as well as other factors. While scoring systems have been developed by combining certain preoperative fac- tors, these have been inconsistent in accurately deter- mining prognosis. There has been increasing interest in the use of biologic and molecular markers to predict prognosis following CRLM. The role of markers such as KRAS, BRAF, p53, human telomerase reverse transcrip- tase, thymidylate synthase, Ki-67, and hypoxia inducible factor-1α and their correlation with accurately predict- ing survival after surgical resection have been sup- ported by several studies. Furthermore, other elements such as pathological response to chemotherapy and the presence of circulating tumor cells have shown promise in accurately determining prognosis after resection for colorectal liver *** herein review past, present, and possible future markers of prognosis among colorectal cancer patients with liver metastasis undergo-ing resection with curative intent.

关键词： Colorectal Metastasis Prognosis Risk score Molecular markers Outcomes

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Helping to address the over treatment of prostate cancer： tools to differentiate lethal and non-lethal phenotype in prostate cancer

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Asian Journal of Andrology 2012年第3期14卷 347-348页

作者： Professor Robert H Getzenberg Professor H Ballentine Carter Department of Urology The Brady Urological Institute Johns Hopkins Hospital Baltimore MD 21287 USA Department of Urology The Johns Hopkins University School of Medicine and The James Buchanan Brady Urological Institute The Johns Hopkins Hospital Baltimore MD 21287 USA

2011 was a noteworthy year for those interested in the care of patients with prostate cancer. First, the US Preventive Services Task Force （USPSTF） released an update on prostate cancer screening, and recommended against the use of the prostate-specific antigen （PSA） test for all men, regardless of family history or race. While this surprised many in the field, the conclusion that there is more harm than benefit is inescapable on a population level--the focus of the USPSTF. Most men with newly diagnosed prostate cancer have favorable risk disease and are at an age when treatment is unlikely to extend life---a conclusion that is supported by randomized trials. Second, the National institutes of Health convened a ＇State of the Science＇ conference on active surveillance for prostate cancer, and concluded that the rates of overtreatment of prostate cancer are high and surveillance is greatly underutilized. Both the USPSTF and the National institutes of Health conference were prompted in large part by the recognition that widespread PSA testing leads to prostate biopsies that often uncover indolent disease. In the majority of cases,

关键词： Helping prostate cancer

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Clinical features and visual outcomes of scleritis patients presented to tertiary care eye centers in Saudi Arabia

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International Journal of Ophthalmology(English edition) 2015年第6期8卷 1215-1219页

作者： Mohammad Al Barqi Ashley Behrens Abdullah M.Alfawaz Anterior Segment Division King Khaled Eye Specialist Hospital wilmer Eye institute Johns Hopkins University School of Medicine Department of Ophthalmology College of Medicine King Saud University

AIMTo describe the clinical features, systemic associations, treatment and visual outcomes in Saudi patients with *** retrospective chart review was performed for patients with scleritis presenting to two tertiary care eye hospitals in Riyadh, Saudi Arabia, from 2001 to 2011. Data were collected on the clinical features of scleritis, subtypes of scleritis, associated systemic disease, history of previous ocular surgery and medical therapy, including the use of immunosuppressants. Treatment outcomes were evaluated based on best-corrected visual acuity (BCVA) and response to *** the 52 patients included in the study, non-necrotizing anterior scleritis was the most common type of scleritis in 22 patients (42.3%), followed by posterior scleritis in 14 patients (26.9%). The majority of cases, 31 patients (59.6%), were idiopathic in nature. Systemic associations were present in 12 patients (23.1%). Infectious scleritis was confirmed in 6 patients (11.5%): 3 with bacterial scleritis after pterygium excision, 2 patients with scleritis related to tuberculosis and 1 patient with scleritis resulting from herpes simplex infection. For the various subtypes of scleritis, BCVA values after treatment and time to remission significantly differed (P<0.05, all cases). Systemic immunosuppressive therapies in addition to steroids were administered to 46.2% of all patients. The T-sign was present on B-scan ultrasonography in 9 (64.3%) of the 14 posterior scleritis ***-necrotizing anterior scleritis was the most common subtype of scleritis. Final visual outcome and time to remission differed among the various scleritis subtypes.

关键词： autoimmune scleritis scleromalacia episcleritis necrotizing immunosuppressive therapy

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Differentiation of lethal and non lethal prostate cancer： PSA and PSA isoforms and kinetics

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Asian Journal of Andrology 2012年第3期14卷 355-360,I0004页

作者： H Ballentine Carter Department of Urology Johns Hopkins University School of Medicine Johns Hopkins Hospital Baltimore MD 21287-2101 USA

Prostate-specific antigen （PSA） testing for the early diagnosis of prostate cancer has led to a decrease in cancer mortality. However, the high prevalence of low-grade prostate cancer and its long natural history, competing causes of death in older men and treatment patterns of prostate cancer, have led to dramatic overtreatment of the disease. Improved markers of prostate cancer lethality are needed to reduce the overtreatment of prostate cancer that leads to a reduced quality of life without extending life for a high proportion of men. The PSA level prior to treatment is routinely used in multivariable models to predict prostate cancer aggressiveness. PSA isoforms and PSA kinetics have been associated with more aggressive phenotypes, but are not routinely employed as part of prediction tools prior to treatment. PSA kinetics is a valuable marker of lethality post treatment and routinely used in determininE the need for salva=e theraov.

关键词： benign PSA human kallikrein 2 precursor form of PSA prostate specific antigen PSA kinetics unbound or free PSA

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Indirect traumatic optic neuropathy

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Journal of Medical Colleges of PLA(China) 2016年第2期31卷 87-92页

作者： Eric L.Singman Nitin Daphalapurkar Helen White Thao D.Nguyen Lijo Panghat Jessica Chang Timothy McCulley wilmer Eye institute at johns hopkins hospital BaltimoreMarylandUSA Whiting School of Engineering Johns Hopkins UniversityBaltimoreMDUSA Walter Reed National Military Medical Center BethesdaMDUSA

Indirect traumatic optic neuropathy(ITON) refers to optic nerve injury resulting from impact remote to the optic nerve. The mechanism of injury is not understood, and there are no confirmed protocols for prevention, mitigation or treatment. Most data concerning this condition comes from case series of civilian patients suffering blunt injury, such as from sports- or motor vehicle-related concussion, rather than military-related ballistic or blast damage. Research in this field will likely require the development of robust databases to identify patients with ITON and follow related outcomes, in addition to both in-vivo animal and virtual human models to study the mechanisms of damage and potential therapies.

关键词： Indirect trauma Optic nerve Blunt Blast Neuropathy Biomechanics Virtual model

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