Surgical treatment of thyroid-related lower eyelid retraction: a modified approach.

A 15-year retrospective study was performed in 68 patients who underwent scleral implantation for correction of lower eyelid retraction related to Graves' disease. Three variations of the scleral implantation procedure were used over three time periods. Scleral grafting alone ("old" procedure) was performed in 53 patients from 1974 to 1985. Because of persistent lower lid retraction postoperatively, this procedure was modified. Beginning in 1986, a lateral canthal suspension consisting of either a lateral tarsal strip or a lateral tarsorrhaphy was added to the scleral implantation ("intermediate" procedure) and was performed in seven patients. Since 1988, the procedure has been further modified to include both a lateral tarsal strip and a lateral tarsorrhaphy ("new" procedure). Eight patients underwent this procedure. Analysis with Student's t test indicated a statistically significant reduction in lower lid retraction when using the new procedure, as measured by a reduction in the margin reflex distance-2, the distance from the corneal light reflex to the central lower lid (p = 0.02), and by a reduction in inferior central scleral show, the distance from the central lower lid to the inferior limbus (p = 0.02). An analysis of covariance, controlling for age, Hertel exophthalmometry readings, and length of follow-up, also indicated that the reduction in the postoperative margin reflex distance-2 was significant (p = 0.04).     

Enhanced Retroviral Transduction of 5-Fluorouracil-Resistant Human Bone Marrow (Stem) Cells Using a Genetically Modified Packaging Cell Line

Pluripotent hematopoietic stem cells (PHSC) are rare cells capableof multilineage differentiation, long-term reconstituting activity andextensive self-renewal. Such cells are the logical targets for manyforms of corrective gene therapy, but are poor targets for retroviralmediated gene transfer owing to their quiescence, as retroviraltransduction requires that the target cells be cycling. To try andsurmount this problem we have constructed a retroviral producer linethat expresses the membrane-bound form of human stem cell factor (SCF)on its cell surface. These cells are capable, therefore, of deliveringa growth signal concomitant with recombinant retroviral vectorparticles. In this report we describe the use of this cell line totransduce a highly quiescent population of cells isolated from adulthuman bone marrow using the 5-fluorouracil (FU) resistance technique ofBerardi et al. Quiescent cells selected using this technique weretransduced by cocultivation with retroviral producers expressingsurface bound SCF or with the parent cell line that does not. Followingcoculture, the cells were plated in long-term bone marrow culture for afurther 5 weeks, before plating the nonadherent cells in semisolidmedia. Colonies forming in the semisolid media over the next 14 dayswere analyzed by polymerase chain reaction for the presence of theretroviral vector genome. Over six experiments, the transductionfrequency of the quiescent 5-FU resistant cells using theSCF-expressing producer line averaged about 20%, whereas thosetransduced using the parent producer line showed evidence of reducedlevels or no transduction.     

Growth and Differentiation of Transplanted W/Wv Marrow

This paper reports new data on the effect of the action of the mutant genesW and W^v on murine hemopoiesis. Our studies demonstrate that the presenceof these mutant genes produces: (1) a macrocytic anemia with neithergranulocytopenia nor thrombocytopenia; (2) a severe defect in the earlystages of hemopoietic repopulation manifested by (a) an apparent block inthe differentiation of immature cells into erythroid precursors, and (b) a greatly reduced rate of proliferation of differentiated hemopoietic elements.

These data demonstrate the existence of genetic influence on repopulationand differentiation of transplanted marrow and suggest that severe anemia mayresult not only from defects in the late stages of erythroid development butalso from abnormalities in the early stages of erythroid maturation andhemopoietic repopulation.

Submitted on February 15, 1967 Accepted on May 5, 1967     

山东省县级综合医院绩效考核评价研究

目的全面评估山东省县级综合医院的整体服务与技术水平,进一步落实县级综合医院的功能定位,引导其发展方向。方法以文献研究为基础,综合应用专家咨询法、倍数环比法确定指标构成及权重,并通过TOPSIS法、定量分析与对比分析等方法,研究山东省111家县级综合医院的绩效考核情况。结果山东省县级综合医院发展水平参差不齐,运营效率与持续发展方面存在明显劣势。结论各县级综合医院应根据实际情况调整未来发展重心,加强规范化管理,促进各指标协同发展。同时,政府应继续落实对县级综合医院的扶持政策。     

Tissue plasminogen activator concentration dependence of 120 kHz ultrasound-enhanced thrombolysis

It has been known for some time that the application of ultrasound can enhance the efficacy of thrombolytic medications such as recombinant tissue plasminogen activator (rt-PA). Potential clinical applications of this ultrasound-enhanced thrombolysis (UET) include the treatment of myocardial infarction, acute ischemic stroke, deep venous thrombosis and other thrombotic disorders. It may be possible to reduce the dose of rt-PA while maintaining lytic efficacy; however there is little data on the rt-PA concentration dependence of UET. In this work, the rt-PA concentration dependence of clot lysis resulting from 120 kHz UET exposure was measured in an in vitro human clot model. Clots were exposed to rt-PA for 30 min, with (UET treated) or without 120 kHz ultrasound (rt-PA treated) at 37 degrees C, and the clot width measured as a function of time. The rt-PA concentration ranged from 0-10 microg/mL. The initial lytic rate for the UET-treated group was greater than that of the rt-PA group at almost all rt-PA concentrations, and exhibited a maximum over concentration values of 1-3 microg/mL.     

Long-Term Complete Clinical and Hematological Response With Bortezomib: The Report of a Case With TEM(P)I Syndrome and a Review of the Literature

TEMPI syndrome was first defined in 2011 and classified as a plasma cell neoplasm with associated paraneoplastic syndrome in 2016. The pathogenesis of the syndrome is not well understood. Recognition of a combination of telangiectasia, erythrocytosis with a high erythropoietin level, monoclonal gammopathy, perinephric fluid collection, and intrapulmonary shunt is the first step in managing the disease. Diagnoses are often delayed because the syndrome is rare and can be mistaken for other dermatological, renal, and pulmonary disorders. Without early diagnosis significant disability results from the pulmonary damage. The article we present here describes a clinical case of TEMPI-syndrome in a 58-year-old woman, which illustrates the difficulties associated with the timely recognition of this unusual disease. Here, we also review the clinical features of TEMPI syndrome, differential diagnosis and available treatment options, based on current literature. Although limited in number, with the addition of new patients to the literature, TEMPI syndrome is evolving into a well characterized multisystem syndrome. This rare disorder should not be missed, especially if the patient has a putative diagnosis of essential telangiectasia with a monoclonal gammopathy and polistemia. Increasing the awareness of clinicians about the disease and adding new patient data to the literature may contribute to a better understanding of the pathophysiology of the disease and standardization of treatment.     

Autism spectrum disorders may be due to cerebral toxoplasmosis associated with chronic neuroinflammation causing persistent hypercytokinemia that resulted in an increased lipid peroxidation,oxidative stress,and depressed metabolism of endogenous and exogenous substances

Worldwide, approximately 2 billion people are chronically infected with Toxoplasma gondii with largely yet unknown consequences. Patients with autism spectrum disorders (ASD) similarly as mice with chronic toxoplasmosis have persistent neuroinflammation, hypercytokinemia with hypermetabolism associated with enhanced lipid peroxidation, and extreme changes in the weight resulting in obesity or wasting. Data presented in this review suggest that environmental triggering factors such as pregnancy, viral/bacterial infections, vaccinations, medications, and other substances caused reactivation of latent cerebral toxoplasmosis because of changes in intensity of latent central nervous system T. gondii infection/inflammation and finally resulted in development of ASD. Examples of such environmental factors together with their respective biomarker abnormalities are: pregnancy (increased NO, IL-1β, TNF-α, IL-6, IL-10, prolactin; decreased IFN-γ, IL-12), neuroborreliosis (increased IL-1β, sIL-1R2, TNF-α, IFN-γ, IL-6, IL-10, IL-12, IL-18, transforming growth factor-β1 (TGF-β1)), viral infections (increased IL-1β, IL-6, IL-8, TNF-α, IFN-γ/α/β, TGF-β1), thimerosal (increased IL-5, IL-13; decreased IFN-γ, TNF-α, IL-6, IL-12p70, NOS), and valproic acid (increased NO, reactive oxygen species; decreased TNF-α, IL-6, IFN-γ). The imbalances in pro- and antiinflammatory processes could markedly hinder host defense mechanisms important for immune control of the parasite, such as the production of NO, cytokines, and reactive oxygen/nitrogen species, tryptophan degradation by indoleamine 2,3-dioxygenase and/or tryptophan 2,3-dioxygenase, limitation of the availability of intracellular iron to T. gondii, and the mechanisms mediated by an IFN-γ responsive gene family. These fluctuations could result in a recurrent profuse multiplication of T. gondii in the brain associated with persistent neuroinflammation, chronic overproduction of pro- and antiinflammatory cytokines, and NO causing increased oxidative stress, and significantly depressed activity of several enzymes including cytochrome P450 monooxygenase family responsible for metabolism of physiological substrates and xenobiotics, such as steroids, fatty acids, prostaglandins, drugs, pollutants, and carcinogens, finally leading to development of ASD. This reasoning may be supported by such abnormal metabolic events as: (1) patients with ASD have significantly decreased melatonin levels caused by marked deficit in acetylserotonin methyltransferase activity, possibly resulting from maternal and/or fetal/postnatal overproduction of NO, characteristic for this clinical entity; (2) thimerosal inhibited both insulin-like growth factor-1- and dopamine-stimulated methylation reactions, and depressed methionine synthase activity, the metabolic events important for promoting normal neurodevelopment; (3) valproic acid, a strong histone deacetylase inhibitor, have potent anti-T. gondii activity. Thus, patients with ASD should be tested for T. gondii infection.