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Introduction: At the present time, the skin tumors are among the most common cancers. Optimal therapy is based on the extent of the disease and the age of the patient. The need for radiotherapy occurs for inoperable locally advanced tumors and in the event of failure, salvage surgery is applied., Materials and Methods: We provided a case report of an older patient with giant squamous cell skin carcinoma and a review of published articles., Results: We present a rare case of giant squamous cell skin carcinoma with metastatic satellite tumors that was primarily treated with curative radiotherapy. Five months after radiotherapy, a recurrent tumor was detected at the site of origin and the treatment was completed by salvage surgery. Full remission was achieved for four years., Conclusion: Despite the seemingly incurable finding it is always necessary to consider radical treatment regardless of the patient´s age. Curative treatment could achieve long term remission in the group of older patients., (© 2019 Greater Poland Cancer Centre. Published by Elsevier B.V. All rights reserved.)

Purpose: Chronic Achilles tendinopathy is one of the most common causes of malfunction and pain, which can lead to a significant reduction of the quality of life. The hypothesis of this study argues that autologous conditioned serum (i.e. Orthokine) injections in chronic midportion Achilles tendinopathy have a better outcome than eccentric training., Methods: This study investigates, retrospectively, the effects of peritendinous autologous conditioned serum injections as compared to standard eccentric training in 50 patients with chronic Achilles tendinopathy between 2012 and 2015. Before injection or eccentric training and 6 weeks, 12 weeks and 6 months thereafter, the patients were assessed by means of the VISA-A-G score (Victorian Institute of Sport Assessment-Achilles questionnaire-German). An MRI was also performed before and 6 months after injection and eccentric training., Results: Both patient groups had statistically significant better VISA-A-G scores after injection or eccentric training compared to the baseline before injection (90 vs 40, respectively, P < 0.001) or eccentric training (81 vs 47, respectively, P < 0.001). Comparing the baseline corrected VISA-A-G scores, patients in the autologous-conditioned-serum-group had significantly higher changes in VISA-A-G scores than the eccentric-training-group after 12 weeks (40 vs 36, P = 0.018) and 6 months (50 vs 34, P = 0.034). Both patient groups had statistically significant (P < 0.001) reduction of tendon thickness (autologous conditioned serum: 0.32; eccentric training: 0.24) and length of bursa (autologous conditioned serum: 0.24; eccentric training: 0.21) as well as significant (P < 0.001) improvement of tendon quality in MRI (autologous conditioned serum: 14 vs 1; eccentric training: 14 vs 2). There were no statistical differences in MRI-findings between the two groups., Conclusion: Both therapies led to improvement of MRI-findings, including reduction of tendon thickness and tendon quality. Autologous-conditioned-serum-injections show greater clinical long-term benefit as compared to eccentric training and, therefore, offers a good alternative to eccentric training., Level of Evidence: Therapeutic studies, Level III.

Patient, caregiver, and family education and support was 1 of 6 key areas of interest identified by the National Marrow Donor Program/Be The Match 2-year project to prioritize patient-centered outcomes research (PCOR) goals for the blood and marrow transplantation (BMT) community. PCOR focuses on research to help patients and their caregivers make informed decisions about health care. Therefore, each area of interest was assigned to a working group with broad representation, including patients, caregivers, and clinicians. Each working group was charged with identifying gaps in knowledge and making priority recommendations for critical research to fill those gaps. The report from this working group presents a conceptual framework to address gaps in knowledge regarding patient and caregiver education in BMT and recommendations for priority research questions on this topic., (Copyright © 2019. Published by Elsevier Inc.)

The goal of patient-centered outcomes research (PCOR) is to help patients and those who care for them make informed decisions about healthcare. However, the clinical research enterprise has not involved patients, caregivers, and other nonproviders routinely in the process of prioritizing, designing, and conducting research in hematopoietic cell transplantation (HCT). To address this need the National Marrow Donor Program/Be The Match engaged patients, caregivers, researchers, and other key stakeholders in a 2-year project with the goal of setting a PCOR agenda for the HCT community. Through a collaborative process we identified 6 major areas of interest: (1) patient, caregiver, and family education and support; (2) emotional, cognitive, and social health; (3) physical health and fatigue; (4) sexual health and relationships; (5) financial burden; and (6) models of survivorship care delivery. We then organized into multistakeholder working groups to identify gaps in knowledge and make priority recommendations for critical research to fill those gaps. Gaps varied by working group, but all noted that a historical lack of consistency in measures use and patient populations made it difficult to compare outcomes across studies and urged investigators to incorporate uniform measures and homogenous patient groups in future research. Some groups advised that additional pre-emptory work is needed before conducting prospective interventional trials, whereas others were ready to proceed with comparative clinical effectiveness research studies. This report presents the results of this major initiative and makes recommendations by working group on priority questions for PCOR in HCT., (Copyright © 2018 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

A projected shortage of hematopoietic cell transplantation (HCT) health professionals was identified as a major issue during the National Marrow Donor Program/Be The Match System Capacity Initiative. Work-related distress and work-life balance were noted to be potential barriers to recruitment/retention. This study examined these barriers and their association with career satisfaction across HCT disciplines. A cross-sectional, 90-item, web-based survey was administered to advanced practice providers, nurses, physicians, pharmacists, and social workers in 2015. Participants were recruited from membership lists of 6 professional groups. Burnout (measured with the Maslach Burnout Inventory subscales of emotional exhaustion and depersonalization) and moral distress (measured by Moral Distress Scale-Revised) were examined to identify work-related distress. Additional questions addressed demographics, work-life balance, and career satisfaction. Of 5759 HCT providers who received an individualized invitation to participate, 914 (16%) responded; 627 additional participants responded to an open link survey. Significant differences in demographic and practice characteristics existed across disciplines (P < .05). The prevalence of burnout differed across disciplines (P < .05) with an overall prevalence of 40%. Over one-half of pharmacists had burnout, whereas social workers had the lowest prevalence at less than one-third. Moral distress scores ranged from 0 to 336 and varied by discipline (P < .05); pharmacists had the highest mean score (62.9 ± 34.8) and social workers the lowest (42.7 ± 24.4). In multivariate and univariate analyses, variables contributing to burnout varied by discipline; however, moral distress was a significant contributing factor for all providers. Those with burnout were more likely to report inadequate work-life balance and a low level of career satisfaction; however, overall there was a high level of career satisfaction across disciplines. Burnout, moral distress, and inadequate work-life balance existed at a variable rate in all HCT disciplines, yet career satisfaction was high. These results suggest specific areas to address in the work environment for HCT health professionals, especially the need for relief of moral distress and a greater degree of personal time. As the creation of healthy work environments is increasingly emphasized to improve quality care and decrease costs, these findings should be used by HCT leadership to develop interventions that mitigate work-related distress and in turn foster recruitment and retention of HCT providers., (Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

Hematopoietic cell transplantation (HCT) survivors are at risk for development of late complications and require lifelong monitoring for screening and prevention of late effects. There is an increasing appreciation of the issues related to healthcare delivery and coverage faced by HCT survivors. The 2016 National Institutes of Health Blood and Marrow Transplant Late Effects Initiative included an international and broadly representative Healthcare Delivery Working Group that was tasked with identifying research gaps pertaining to healthcare delivery and to identify initiatives that may yield a better understanding of the long-term value and costs of care for HCT survivors. There is a paucity of literature in this area. Critical areas in need of research include pilot studies of novel and information technology supported models of care delivery and coverage for HCT survivors along with development and validation of instruments that capture patient-reported outcomes. Investment in infrastructure to support this research, such as linkage of databases including electronic health records and routine inclusion of endpoints that will inform analyses focused around care delivery and coverage, is required., (Copyright © 2017 The American Society for Blood and Marrow Transplantation. All rights reserved.)

In the United States, insurance status has been implicated as a barrier to obtaining timely treatment. In this retrospective cohort study of 521 patients who underwent first hematopoietic cell transplantation (HCT), we investigated the association between timeliness of HCT and overall survival. Timeliness was operationally defined in the following 3 ways: (1) payer approval, from request for approval to actual payer approval; (2) transplantation speed, from payer approval to time of actual HCT; and (3) total time, from request for approval to HCT. Patients with private insurance had longer time to payer approval (P < .0001) than those with public payers but shorter time from approval to actual HCT (P < .0001) and total time to HCT (P < .0001). Multivariate Cox regression showed no significant differences in risk of death between slow and fast times in the 3 indices of timeliness in the models that used all patients (n = 509), autologous HCT in lymphoma (n = 278), and autologous HCT in multiple myeloma (n = 121). Additional studies to evaluate the effect of insurance timeliness on all patients for whom HCT is recommended, not just those who undergo HCT, should be conducted., (Copyright © 2016 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

Unlabelled: We reviewed original research papers that used quantifiable technology to detect early autism spectrum disorder (ASD) and identified 376 studies from 34 countries from 1965 to 2013. Publications have increased significantly since 2000, with most coming from the USA. Electroencephalogram, magnetic resonance imaging and eye tracking were the most frequently used technologies., Conclusion: The use of quantifiable technology to detect early ASD has increased in recent decades, but has had limited impact on early detection and treatment. Further scientific developments are anticipated, and we hope that they will increasingly be used in clinical practice for early ASD screening, diagnosis and intervention., (©2015 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

On the basis of (7)Li NMR experiments, the complex-formation reaction between Li(+) and the tridentate N-donor ligand terpyridine was studied in the ionic liquids [emim][NTf2] and [emim][ClO4] as solvents. For both ionic liquids, the NMR data implicate the formation of [Li(terpy)2](+). Density functional theory calculations show that partial coordination of terpyridine involving the coordination of a solvent anion can be excluded. In contrast to the studies in solution, X-ray diffraction measurements led to completely different results. In the case of [emim][NTf2], the polymeric lithium species [Li(terpy)(NTf2)]n was found to control the stacking of this complex, whereas crystals grown from [emim][ClO4] exhibit the discrete dimeric species [Li(terpy)(ClO4)]2. However, both structures indicate that each lithium ion is formally coordinated by one terpy molecule and one solvent anion in the solid state, suggesting that charge neutralization and π stacking mainly control the crystallization process.

The National Marrow Donor Program, in partnership with the American Society for Blood and Marrow Transplantation, sponsored and organized a series of symposia to identify complex issues affecting the delivery of hematopoietic cell transplantation (HCT) and to collaboratively develop options for solutions. "Hematopoietic Cell Transplantation in 2020: A System Capacity Initiative" used a deliberative process model to engage professional organizations, experts, transplant centers, and stakeholders in a national collaborative effort. Year 2 efforts emphasized data analysis and identification of innovative ideas to increase HCT system efficiency, address future capacity requirements, and ensure adequate reimbursement for HCT programs to meet the projected need for HCT. This report highlights the deliberations and recommendations of Year 2 and the associated symposium held in September 2011., (Copyright © 2013 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

Hematopoietic cell transplantation (HCT) is the only known curative therapy for many patients with life-threatening hematologic and oncologic diseases. It is estimated that the National Marrow Donor Program(®) (NMDP) will facilitate 10,000 transplants by 2015, double the current number. To better understand the existing personnel and center infrastructure for HCT in the country and to address system capacity challenges to the future growth of HCT, the NMDP convened a diverse group of stakeholders and thought leaders representing HCT physicians, physician assistants, nurse practitioners, nurses, pharmacists, other healthcare providers, HCT program directors, hospital administrators, payors, and professional organizations. Working groups were formed to identify: capacity issues because of shortages in human resources, structural constraints, and patient access barriers including diversity and healthcare disparity challenges; recommendations to address challenges; and stakeholders to engage. This report details the deliberations and recommendations of a national symposium, "Hematopoietic Cell Transplantation in 2020: A Health Care Resource and Infrastructure Assessment," held in September 2010., (Copyright © 2012 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

Postoperative diplopia and strabismus may result from a variety of ocular surgical procedures. Common underlying mechanisms include sensory disturbance, scarring, direct extraocular muscle injury, myotoxicity from injections of local anesthesia or antibiotics, and malpositioning of extraocular muscles by implant materials. The most common patterns are vertical and horizontal motility disturbance. Treatment options include prisms, botulinum, occlusion, or surgery., (Copyright 2010 Elsevier Inc. All rights reserved.)

Autologous hematopoietic stem cell transplantation (HSCT) is a potentially curative therapeutic approach for various malignant hematologic and lymphoid diseases. Hematopoietic stem cells (HSCs) may be collected from the blood or the bone marrow. HSCs are capable of self-renewal and give rise to progenitor cells, multipotent cells that differentiate and proliferate into the mature cells of the blood and immune system. HSCs and progenitor cells are released from the bone marrow into the peripheral blood through a process called mobilization. HSCs then are collected from the blood in a process called apheresis and cryopreserved for administration following the high-dose preparative regimen. This article reviews stem cell biology, current mobilization strategies, use of novel mobilization agents, and nursing care of patients during the mobilization phase of autologous HSCT. Understanding the biology and process of HSC mobilization is critical for transplantation nurses to deliver and coordinate care during this complex phase of autologous HSCT.

Purpose/objectives: To examine practice variation in hematopoietic stem cell transplantation (HSCT) nursing and to identify the gap between recommended standards of practice and actual practice across settings. Additional practices relevant to HSCT nursing also were explored., Research Approach: Cross-sectional, descriptive survey., Setting: National and international cancer centers., Participants: A convenience sample was obtained from the 2006 Oncology Nursing Society Blood and Marrow Stem Cell Transplant Special Interest Group membership list (N = 205). Most participants were women (94%) with a median age of 45 years. The primary role was bedside nurse (46%), with an adult-only population (78%) in an academic (84%), inpatient (68%-88%) center. 39 (94%) U.S. states and 7 (6%) non-U.S. countries were represented., Methodologic Approach: Survey development was guided by Dillman Mail and Internet survey design. Electronic questionnaires were conducted with Zoomerang Market Tools., Main Research Variables: Infection control practices across bone marrow transplantation settings., Findings: Descriptive statistics revealed minimal practice variation regarding infection control across transplantation types or conditioning regimens. Practices regarding implementation of restrictions on patients' hygiene, diet, and social interactions varied by phase of transplantation, with the greatest variations occurring during the post-transplantation phase. Sixty-two percent of respondents reported using published guidelines; 72% reported using organization-specific policies., Conclusions: Although published standards are under consideration, practice variation exists across transplantation centers. Whether the variation is caused by a lack of compliance with published guidelines or by the poor delineation of details for providers to translate the guidelines into practice is not known., Interpretation: Identifying gaps in the literature and inconsistencies in HSCT practices is an important first step in designing evidence-based projects that can be used to standardize practice and link best practices to improved patient outcomes.

Background: Catheter-associated infections markedly contribute to treatment failure in peritoneal dialysis (PD) patients. There is much controversy surrounding prophylactic strategies to prevent these infections., Methods: In this nationwide multicenter study we analyzed strategies to prevent catheter-associated infections as performed in Austrian PD centers in 2006. A questionnaire was sent to all 23 PD centers in Austria., Results: Ten different catheter models were used in the 332 patients being treated in the 23 Austrian PD centers. Systemic antibiotics prior to catheter placement were given by 17 of the 23 PD centers (glycopeptides, n = 7; cephalosporins, n = 10). Nasal swabs were taken preoperatively by 17 PD centers; nasal Staphylococcus aureus carriers were treated prophylactically with mupirocin cream in 15 of these centers. Dressing change was routinely performed in 318 of 332 chronic PD patients (nonocclusive film dressing, n = 58; gauze dressing, n = 260). Disinfectants for chronic exit-site care included povidone iodine (n = 155), sodium hypochlorite (n = 31), povidone iodine + sodium hypochlorite together (n = 102), and octenidine dihydrochloride/phenoxyethanol (n = 17). Water + non-disinfectant soap or 0.9% sodium chloride was administered as a cleansing agent to the exit site by 27 patients. Routine S. aureus screening (nasal and/or exit-site swabs) in chronic PD patients was performed in 12 PD centers; carriers were treated with mupirocin cream in 11 of these centers. Dialysis staff members were screened for S. aureus in 8 PD centers and spouses were screened for S. aureus in 5 PD centers. The overall exit-site infection rate was 1 episode/43.9 patient-months, tunnel infection rate was 1 episode/88.9 patient-months, and peritonitis rate was 1 episode/51.0 patient-months. Patients of centers that have installed a prophylaxis protocol for treating S. aureus carriers had lower mean infection rates compared with those not using such a protocol., Conclusion: Various individual prophylactic strategies are used to prevent catheter-associated infections in Austrian PD centers. Infection rates are within the range reported in the literature. There is still scope for improvement in some centers (e.g., by establishing a prophylaxis protocol).

Objectives: To provide an overview of the indications for hematopoietic stem cell transplantation (HSCT), including standard-of-care and experimental diseases., Data Sources: Research studies, book chapters, websites, and articles describing diseases treated with HSCT., Conclusion: The indications for HSCT are continually changing and expanding rapidly beyond the traditional use as a treatment for malignant and non malignant diseases., Implications for Nursing Practice: Nurses who care for transplant patients will need to become knowledgeable of not only the diseases treated traditionally with HSCT, but also the many other diseases or disorders in which HSCT may play a role.

We review the growth factor receptor-mediated cell signaling events that induce the responses required for the maintenance of corneal epithelial health. Our focus is to show how such responses contribute to sustaining corneal transparency and deturgescence, so basic to the pathogenesis of corneal diseases. Furthermore, we point out how alterations of receptor-mediated control of these responses account for losses in corneal transparency. In particular, the roles of growth factors in the mediation of normal corneal function, including epithelial cell proliferation, prevention of compromise of the barrier function of the cornea, and maintenance of normal renewal processes are discussed in relation to clinical entities involving the cornea.

Background: Primary and secondary optic nerve sheath meningiomas (ONSMs) are neoplasms that account for a large proportion of optic nerve and orbital tumors. The diagnosis is not always straightforward and is based on the appropriate clinical findings and neuroimaging. Biopsy or surgical intervention may occasionally be necessary but is associated with significant morbidity., Methods: Issues related to clinical signs and symptoms, diagnosis, natural history, and treatment strategies are reviewed based on a review of published literature., Results: Diagnosis is usually based on radiographic and clinical findings. Biopsies are not obtained in most cases, thus adding further to the bias of possible misdiagnosis in all reported case series that do not have the benefit of histopathologic confirmation. Natural history typically shows inexorable progression in most cases, although long periods of stability are occasionally reported. Treatment options include observation, radiation alone, surgery alone, and combined radiation and surgery. The optimum timing of interventional therapy and radiation are evolving., Conclusions: After serial examination documents new decline in acuity and/or visual field, fractionated radiotherapy appears most likely to preserve visual function and is a valid treatment approach for primary orbital ONSM. Tumor enlargement, as determined by serial imaging, may also provide an indication to begin radiotherapy.

Competition among healthcare institutions, the need to improve outcomes, and the desire to decrease costs have motivated blood and marrow stem cell transplant centers to develop innovative care models. In an effort to meet these challenges, a major midwestern medical center adapted the transplant process to the outpatient setting. This transition created greater educational and care demands for patients and families. To address these demands and provide improved accommodations and amenities for patients and families, the center adopted an innovative model of care, Cooperative Care, for transplant recipients. Cooperative Care embraces patients and families as key members of the healthcare team. A family member serves as a primary caregiver for the patient during the acute inpatient phase of the transplant. Care becomes more personal and individualized, cost is reduced, the rate of rehospitalization potentially is decreased, and patients ultimately become more confident and competent in caring for themselves. The healthcare team shifted its care philosophy to incorporate a care partner, increase patient control and independence, and create greater emphasis on education. Outcomes, including patient satisfaction, have demonstrated success and motivated expansion of this model to other patient populations.

The authors performed a retrospective clinicopathologic review of lymphoid tumors of the orbit and ocular adnexa. In addition, we used an immunohistologic marker for proliferating cell nuclear antigen (PCNA), an intranuclear protein with greatest expression in actively proliferating (dividing) cells, to determine whether levels of PCNA can be correlated with the presence or future development of systemic lymphoma. To the authors' knowledge, the present study represents the first in which PCNA indices, i.e., the number of cells that showed diffuse intranuclear staining for PCNA averaged per 10 high power field (HPF), were correlated with systemic disease in orbital and ocular adnexal lymphomas. The percentage of B- and T-cells in the tumor infiltrate was also determined. Followup data showed that two patients with eyelid involvement had preexisting systemic lymphoma, whereas another with bilateral lacrimal gland disease later developed systemic lymphoma. Followup times ranged from 24 to 42 months (mean 39.7 months). The mean PCNA level in three patients with systemic disease was 13.3 and in the six patients with no systemic disease was 33.8. These results suggest that PCNA alone cannot be used as a marker for the presence of, or development into, systemic lymphoma.

Thrombotic occlusion is frequently a complication of central venous catheters (CVCs). The original designers and producers of CVCs recommended heparin flush regimens to prevent thrombosis and maintain patency. This has become standard practice although no studies have demonstrated a relationship between heparin flushing and reduction of catheter thrombosis. Many consider the routine use of heparin flushing innocuous. However, serious complications including drug interactions and heparin induced thrombocytopenia and thrombosis syndrome (HITS) have been reported in association with heparin flushing. Numerous studies comparing heparin to saline flushing in peripheral devices suggest equal rates of thrombotic occlusions. The purpose of this study was to examine the incidence of thrombotic occlusions in CVCs using heparin compared to saline flushing. The study involved 78 cancer patients undergoing apheresis collection for peripheral blood stem cells; 29 received saline flushes and 49 received heparin (100 U/ml of saline) flushes. Study endpoints included slow apheresis flow rate (< 50 ml/min), urokinase use for thrombolysis, and radiographic evidence of catheter thrombosis. No significant differences were found for any endpoint between the two groups. These findings suggest saline may be as effective as heparin for maintaining patency of CVCs.

Purpose: The optimal dose of granulocyte colony-stimulating factor (G-CSF) for mobilization of allogeneic-blood stem cells (AlloBSC) has yet to be determined. As part of a prospective trial, 41 related human leukocyte antigen (HLA)-matched donors had blood cells mobilized with G-CSF at 5 micrograms/kg/d by subcutaneous administration. The purpose of this trial was to monitor adverse effects during G-CSF administration and stem-cell collection, to determine the optimal timing for stem-cell collection, and to determine the cellular composition of stem-cell products following G-CSF administration., Patients and Methods: The median donor age was 42 years. Apheresis began on day 4 of G-CSF administration. At least three daily 12-L apheresis collections were performed on each donor. A minimum of 1.0 x 10(6) CD34+ cells/kg (recipient weight) and 8.0 x 10(8) mononuclear cells/kg were collected from each donor. All collections were cryopreserved in 5% dimethyl sulfoxide and 6% hydroxyethyl starch., Results: Toxicities associated with G-CSF administration and the apheresis process included myalgias/arthralgias (83%), headache (44%), fever (27%), and chills (22%). The median baseline platelet count of 242 x 10(4)/ mL decreased to 221, 155, and 119 x 10(6)/mL on days 4, 5, and 6 of G-CSF administration, respectively. Median numbers of CD34+ cells in collections 1, 2, and 3 were 1.99, 2.52, and 3.13 x 10(6)/kg, respectively. The percentage and total number of CD4+, CD8+, and CD56+/CD3- cells remained relatively constant during the three collections. Median total numbers of cells were as follows: CD34+, 7.73 x 10(6)/kg; and lymphocytes, 6.93 x 10(8)/kg., Conclusion: Relatively low doses of G-CSF can mobilize sufficient numbers of AlloBSC safely and efficiently.

The purpose of the present study was to determine whether proliferating cell nuclear antigen (PCNA), an immunohistochemical marker for a nuclear protein abundant in actively proliferating (dividing) cells, is useful as an aid in differentiating idiopathic orbital inflammatory syndrome (IOIS) from lymphoproliferative lesions (LLs). Records of all patients with IOIS and LLs were studied retrospectively. Tissue biopsy specimens from four patients with IOIS and nine patients with LLs were examined. The diagnosis in each case was based on presenting signs and symptoms, orbital computed tomography (CT) and/or magnetic resonance (MR) scans, histopathologic criteria, and follow-up data consistent with the entity. These findings were correlated with the percentage of B- and T-cells in the lesions as well as with the number of cells that demonstrated staining for PCNA in formalin-fixed tissue. PCNA activity was markedly increased in the higher grade (HG) lymphoma group as compared to that in the low grade (LG) lymphoma and idiopathic inflammatory group. Lymphoma cases showed a significantly increased B-/T-cell ratio compared to IOIS lesions. PCNA activity in conjunction with the ratio of B-/T-cells may be a helpful immunohistologic adjunct for differentiating purely inflammatory lesions of the orbit from lymphoid tumors. Further studies are necessary to compare PCNA activity in fresh frozen tissue with that in formalin-fixed tissue.

Purpose: Mobilization of peripheral-blood cells (PBC) with cytokines alone results in rapid hematopoietic recovery and avoids the potential morbidity associated with mobilization by chemotherapy. PIXY321, a fusion protein that consists of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-3 (IL-3), has enhanced hematopoietic colony-forming activity as compared with individual or equimolar combinations of the two cytokines. A phase I trial of PIXY321 for mobilization of PBC in patients with malignant lymphoma was performed., Patients and Methods: Thirteen patients with malignant lymphoma who were eligible for high-dose therapy (HDT) were enrolled onto the trial. All patients were ineligible for autologous bone marrow transplantation due to overt metastatic disease in the marrow or to severe marrow hypocellularity. PIXY321 was administered at three dose levels of 250, 500, and 750 micrograms/m2/d by continuous infusion until completion of PBC collections. Collections were initiated when the WBC count was greater than 10 x 10(9)/L or 4 days after the initiation of PIXY321, whichever came first. Collections were continued until a minimum of 6.5 x 10(8) mononuclear cells (MNC)/kg patient weight were obtained., Results: PIXY321 was generally well tolerated. Side effects associated with PIXY321 administration did not exceed grade 2 and included fever (85%), chills/sweats (54%), myalgias (38%), fatigue (31%), nausea/vomiting (31%), headache (31%), edema (23%), and rhinorrhea (23%). The median numbers of colony-forming units-granulocyte/macrophage (CFU-GM) in the graft products for the three dose levels were 0.31, 2.94, and 2.88 x 10(4)/kg, respectively; the median numbers of burst-forming units-erythroid (BFU-e) were 0.20, 6.94, and 12.78 x 10(4)/kg, and the median numbers of CD34+ cells were 2.30, 0.74, and 0.39 x 10(6)/kg. Following transplantation, the median times to an absolute neutrophil count (ANC) > 0.5 x 10(9)/L were 12, 15, and 12 days, respectively, and the median times to platelet transfusion independence were 30, 19, and 15 days., Conclusion: PIXY321 can be safely administered and effectively mobilizes PBC in patients with bone marrow defects. PIXY321-mobilized PBC autotransplants result in rapid and sustained hematopoietic recovery.

Patient and family education is an important component of the organ transplant programs at the University of Nebraska Medical Center. The Medical Center is in the process of planning a new transplant center which will employ the family-centered, educationally-intensive cooperative care concept. This approach was chosen as the model for the delivery of care at the Lied Transplant Center because it emphasizes efficient, effective clinical care by requiring active participation by the family or essential other, thereby better preparing both the patient and the family for the transition to home and to the community. This article presents the evolution of patient education in our transplant programs, discusses the educational needs of transplant patients across the continuum of care, provides insight into the process of planning educational programs for the new center and provides a sample module for teaching which is based on the Cooperative Care concept.

No previously published studies have described double-lumen hemodialysis/apheresis catheters for use with continuous-flow apheresis collection of peripheral stem cell (PSC). We prospectively evaluated experiences with these catheters during both PSC collection and transplantation. Because of previously-described successful experiences with single-lumen apheresis catheters placed in the inferior vena cava, all catheters evaluated in this study were placed in this anatomic location. Our experience demonstrated high rates of thrombotic occlusion (65%) and catheter-related infections (15%). This method of access should not be considered optimal in its present state of use. Further investigation into preferred catheter design, anatomic location, and thrombosis prophylaxis during continuous-flow apheresis is warranted.

Diagnosis of ocular cicatricial pemphigoid (OCP), a chronic cicatrizing autoimmune disease of the conjunctiva, may be difficult in the early stages of the disease. We noted abnormal conjunctival scarring in three patients who had undergone eyelid and strabismus surgery, which caused us to suspect OCP. In all three patients who subsequently underwent conjunctival biopsy, immunoglobulin or complement in the basement membrane zone detected by direct immunofluorescence helped establish the diagnosis. Although OCP typically is a disease of the elderly, the three patients in this study were aged < 50 years; one patient was 19 years old. The present study demonstrates that a diagnosis of OCP should be considered for patients who develop abnormal conjunctival scarring after eyelid or strabismus surgery.

The use of split-thickness dermal grafts for successful repair of corneal and scleral defects is reported in 10 patients (11 eyes) who had non-infectious, impending, or overt ocular perforation. In all patients, traditional methods of reconstruction were deemed inappropriate or had already failed. Corneo-scleral defects occurred after various operations: pterygium excision, retinal detachment repair, insertion of a keratoprosthesis (Cardona implant) into an opaque, vascularised cornea, and penetrating keratoplasty. Other causes of corneoscleral defects were scleromalacia perforans, idiopathic systemic vasculitis, alkali burn, ocular cicatricial pemphigoid, and band keratopathy with recurrent erosion following intraocular metallic foreign body. We propose the use of split-thickness grafts: (1) when adjacent conjunctiva is inadequate to cover a corneoscleral defect owing to its large size or great depth or to conjunctival scarring from previous operations, injury, or ocular cicatricial pemphigoid; or (2) as an alternative to autogenous grafts such as conjunctiva, cartilage, fascia lata, tibial periosteum, or mucous membrane as well as to homologous scleral and lamellar grafts. Dermal grafts are advantageous in that they are autogenous, non-antigenic, survive on avascular surfaces, and self-epithelialise and, thus, need not be covered by conjunctiva. Furthermore, they are pliable, have excellent tensile strength, provide ample tectile support, and are abundantly available. Dermal grafts are harvested from the dermal bed of the thigh after an epidermal flap is hinged at one end.

Granulocyte-macrophage colony stimulating factor (GM-CSF) has been used to augment circulating hemopoietic stem cells in the peripheral blood and promote efficient peripheral stem cell (PSC) collection. Anecdotal reports indicate that GM-CSF may contribute to apheresis catheter dysfunction during PSC collection. We prospectively evaluated thrombotic occlusion rate of inferior vena cava (IVC) catheters following introduction of GM-CSF compared with a control group who underwent PSC collection prior to introduction of GM-CSF. Both groups were given aspirin (325 mg daily). The active treatment group was given GM-CSF (starting dose 250 micrograms/m2/day) as continuous infusion via the IVC catheter. The rate of thrombotically occluded catheters increased from 1/29 (3%) to 20/37 (54%) (p < 0.0001). Thrombi developing during GM-CSF therapy were unusual as 25/36 (69%) occlusions cleared with mechanical clot aspiration and did not require lytic agents.

Of 364 patients with lymphoid malignancy who underwent high-dose therapy with autologous bone marrow transplantation (ABMT) or peripheral stem cell transplantation (PSCT), 169 patients have had progressive disease after the procedure. The median survival from the time of relapse for patients with Hodgkin's disease (HD) who progressed after the transplant was 10.5 months. This compares with a median survival of 3 months for relapsed non-Hodgkin's lymphoma (NHL) patients (P = .0036). After failing transplantation, 56 patients were treated with further chemotherapy, 35 with involved field irradiation therapy, and 18 patients were treated with combination chemotherapy and irradiation. Seven patients received biologic therapy and seven patients underwent a second bone marrow transplant. The remainder of the patients were believed to be too ill for further therapy or chose not to receive further treatment for their recurrent lymphoid malignancy. Sixty of the 169 patients with progressive disease after the transplant are still alive; however, only 18 patients are alive off therapy without evidence of active disease after their relapse. Ten of the 18 patients are still less than 12 months past their posttransplant salvage therapy and are at high-risk for relapse. Five patients are progression free at 15 to 36 months after their posttransplant relapse. Only three patients (two NHL and one HD) treated with other modalities after autologous transplant failure are alive without evidence of disease and have been observed at least 4 years postrelapse. Although a few patients will have a durable response to subsequent therapy, the majority of patients who have progressive disease after an autologous transplant for lymphoid malignancy will succumb to recurrent disease within a short period of time.

Eight human corneal lenticules (three from keratophakia, two from hypermetropic keratomileusis, and three from myopic keratomileusis) were examined by light and electron microscopy. The keratophakic lenticules were removed for optical reasons 3, 3.5, and 6 months after surgery. Microscopically, all displayed hypocellularity, mature collagen fibrils and microfibrils, keratocyte ghosts, and keratocytic debris. The hypermetropic keratomileusis specimens were removed at 13 and 14 months postoperatively, the first because of opacities from enzymatic digestion of the cornea, and the second due to contact lens-induced erosion of Bowman's layer and decreased lacrimal secretion. Ultrastructurally, both lenticules exhibited fractures in Bowman's layer, and the 14-month specimen showed multilayered squamous epithelia. The myopic keratomileusis specimens were removed at 4, 8, and 48 months postoperatively due to opacification of the interface caused by delayed epithelial healing, detergent trauma, and previous epithelization, respectively. Electron microscopy revealed fractures in Bowman's layer, subepithelial fibrocellular growth, sparse keratocyte populations of the anterior stroma, porous collagen bundles, keratocytic debris, and regions of epithelial ingrowth.

The ocular pathology of a hemizygous male with Fabry's disease after renal transplantation is reported. The ocular pathology in this patient was essentially identical to that which has previously been reported for both hemizygotes and heterozygotes afflicted with Fabry's disease. Glycolipid deposits and/or osmophilic inclusion bodies were found universally throughout the ocular vasculature. Endothelial, perithelial and smooth muscle cells of the vessel walls were preferentially involved. Iris pigment epithelium was affected as were the corneal epithelium cells. Reduplication of the basement membrane was seen on electron microscopy. Retinal ganglion cells were unaffected. Involvement of the retinal pigment epithelium and the corneal endothelium was documented for the first time.

A white cocoon membrane emanating from an inferotemporal focus in the iris stroma totally ensheathed a Binkhorst four-loop iris plane lens 18 months after implantation. The membrane was removed and studied by scanning (SEM) and transmission (TEM) electron microscopy. By SEM the external surface of the membrane was characterized by a fibrillar meshwork, with only an occasional scattered spindle-shaped or rounded inflammatory cell occupying the surface. One-micron plastic sections revealed both spindle and polyhedral heavily pigmented cells in the outer aspect of the membrane, and compressed elongated nonpigmented spindle cells scattered throughout the central portions. By TEM cells clinging to the outermost aspects were bipolar iris stromal melanocytes with small melanosomes, inactive fibroblasts, or histiocytes with cytoplasmic ruffles. The larger rounded pigmented cells in the superficial region were viable or degenerated iris pigment epithelial cells or macrophages. Most of the substance of the membrane was composed of collagen fibrils 100-500 A in diameter with and without 640 A periodicity; these fibrils were generally oriented parallel to the spindle cells but did not display distinct bundling or a lamellar architecture. The spindle cells in the center of the lesion were active fibroblasts with abundant rough-surfaced endoplasmic reticulum and scattered actin myofilaments; they contained rare small and large melanin granules indicative of phagocytosis. It has been concluded that the membrane was produced predominantly by iris stromal fibroblasts probably activated by the haptics of the IOL or McCanell suture.

Type II glycogenosis is an autosomal recessive storage disease characterized by absence of the enzyme acid alpha-1,4-glucosidase. The eye of a 16 week fetus, aborted after diagnosis by amniocentesis, was studied by light and electron microscopy. Extensive deposits of lysosomal and cytoplasmic glycogen were present in virtually all ocular tissues examined, with the notable exception of pigment epithelia (iris and retina). The massive glycogen deposits present in this, the youngest case thus far examined histologically, emphasize the involvement of the fetus from its earliest stages and the importance of prenatal diagnosis.

Cysticercus cellulosae, the larval stage of Taenia solium, was studied by light and electron microscopy after its removal from the vitreous. The ultrastructure of the larva is highly organized and displays a superficial tegument and deeper parenchyma. The tegument contains a microvillous surface overlying a syncytial cytoplasm. A deeper muscular layer overlies the parenchyma, within which are highly specialized structures important in water balance, flame cells, and acid-neutralizing calcareous corpuscles.

Three new cases of epibulbar choristomas, all containing lacrimal tissue, are presented and compared with those reported previously in the literature. The first and second cases were unilateral, complex choristomas, consisting of ectopic lacrimal tissue, smooth muscle, and cartilage; the first case was also remarkable for the presence of lesional tissue in the peripheral cornea and evidence of progressive growth during puberty. The third case was a bilateral, complex choristoma, manifesting epibulbar lacrimal tissue, cartilage, and smooth muscle; also associated were bilateral optic nervehead colobomas and a uniocular focus of posterior scleral cartilage demonstrated by computed tomography (CT) scanning. On clinical examination, all three lesions displayed highly vascularized thickenings of the conjunctiva with diagnostically useful gelatinous elevations, which corresponded microscopically to lobules of lacrimal tissue. In addition, all three cases had the interesting diagnostic feature of superficial corneal scarring or sclerosis, with a fine vascularity adjacent to the conjunctival lesional tissue. Electron microscopy of the third case demonstrated completely normal cytoarchitecture of the lacrimal tissue. Because of the frequent presence of Müller's smooth muscle in epibulbar lacrimal choristomas, the authors propose that these lesions represent embryologic ectopias or overly extensive field effects of the palpebral lobe of the lacrimal gland.

One hundred and twenty-four small mammals of six species were inoculated with three strains of Colorado tick fever (CTF) virus to define viremia and neutralizing (N) antibody responses. Adult Eutamias minimus and Eutamias embrinus, and juvenile Peromyscus maniculatus and Spermophilus lateralis, were highly susceptible to development of viremic infection. Adult S. lateralis and P. maniculatus were moderately susceptible (greater than or equal to 50% viremic). Five Sylvilagus nuttalli did not become viremic following experimental inoculation. Spermophilus richardsoni was also relatively resistant (less than or equal to 50% viremic). The longest duration of viremia (mean 15.8 days) and highest peak viremia levels (mean peak titer 10(3.9 plaque-forming units per ml) occurred in E. minimus. Adult E. umbrinus, juvenile S. lateralis, and juvenile P. maniculatus had moderate viremias. Adult S. lateralis and S. richardsoni often had short viremias during which virus was only intermittently detectable. N antibody production was most rapid in E. minimus in comparison with other species. In addition, N antibody persisted for 1 year in this species. In other species, many animals lost detectable antibody 5-11 months after infection. No significant differences were found in patterns of infection between three CTF virus strains. We conclude that of the six species inoculated, E. minimus is the best experimental host for CTF virus.

Field studies of Colorado tick fever (CTF) in small mammals in Rocky Mountain National Park (RMNP) in 1974 established that Eutamias minimus and Spermophilus lateralis were the most important hosts for CTF virus and were the source of virus for immature stages of the tick vector, Dermacentor andersoni. Other species (Peromyscus maniculatus, Spermophilus richardsonii, Eutamias umbrinus) are secondary hosts. The intensity of viral activity in rodents varied greatly from locality to locality. Highest rodent infection rates were found to occur in the Moraine Park area of RMNP. Lowest infection rates occurred above 3,290 meters in altitude at Rainbow Curve and on the tundra. The prevalence of infection in rodents was constant from April--July (5--6% of animals captured were viremic) and then declined to 1.7--2.5% in August and September coincident with a decline in nymphal tick ectoparasitism. Many animals were captured which were simultaneously viremic and antibody-positive. Under field conditions, neutralizing antibody seroconversion does not always occur.

A malignant ciliary body melanoma received proton-beam irradiation. After an apparent failure of the tumor to respond, the eye was enucleated. A predominantly epithelioid cell tumor appeared viable by light microscopy, and a low degree of mitotic activity persisted, despite therapy. The tumor cells, however, displayed degenerative changes ultrastructurally, presumably results of the radiotherapy. These consisted of numerous cytoskeletal filaments, lipid vacuoles, prominent phagolysosomes, and nuclear convolutions and fragmentations. The mitochondria were fewer in number in the present tumor than typically encountered in epithelioid cells. A rare leptomeric structure was discovered, probably an organizational modification of the cytoplasmic filaments. The tumor's capillaries showed radiation-induced changes in terms of thickened basement membranes and perivascular fibrin deposition. The foregoing features are indicative of cellular and metabolic injury from the radiotherapy, but these were evidently not sufficiently injurious to sterilize the tumor.

We used split-thickness dermal grafts for the surgical treatment of corneal and scleral perforations in two patients and obtained excellent results. Patient 1 had severe lye burns and bilateral corneal perforations and Patient 2 had scleromalacia perforans. The dermal graft self-epithelializes and, thus, does not need to be covered by conjunctiva; is supple, without the bulkiness of other materials, particularly cartilage and periosteum; is hearty and flourishes on avascular surfaces such as cornea and sclera; has good tensile strength; and is autogenous.

Ecologic studies of small mammals in Rocky Mountain National Park (RMNP) were conducted in 1974 in order to identify the specific habitats within the Lower Montane Forest that support Colorado tick fever (CTF) virus. Data was collected on the abundance and distribution of 4 primary rodent species, tick infestation, CTF virus, and neutralizing antibody prevalence. Rodents were captured along transects crossing different habitats. Open stands of ponderosa pine and shrubs on dry, rocky surfaces were found to be important for maintaining CTF virus.

A 10-year-old white boy presented with a diffuse pigmented lesion of the choroid of his right eye that had led to a partial secondary retinal detachment. Because of the fear of a diffuse choroidal melanoma (a lesion never before reported in an individual within the first two decades of life), the eye was enucleated. An incisional P-32 study, compared with an uninvolved region, was positive at 154% uptake. Pigmented tissue was discovered surrounding the distal meninges of the optic nerve, on the posterior surface of the eye, and within the orbital soft tissues adherent to the globe. This led to fear of extraocular extension of a malignant melanoma. Light microscopic examination of the enucleated globe demonstrated that the choroid was diffusely and massively thickened by polygonal, hyperpigmented tumor cells that were also present in compressed spindled forms between the lamellae of scleral collagen, in the scleral emissaries, on the surface of the eyeball, and in the distal optic nerve dura. The choroidal tumor cells had the features of those normally encountered in localized optic nerve head benign melanocytomas. Electron microscopy demonstrated the presence of large, well-melaninized melanosomes (but no macromelanosomes), confirming the diagnosis of a diffuse uveal melanocytoma. The differential diagnosis of this new entity and its relationship to previously reported pigmented lesions of the uvea is discussed.