Alterations in human vitreous humour following cataract extraction.

Cataract extraction is associated with the risk of posterior vitreous detachment, macular edema and retinal detachment possibly as a result of a disturbance to the vitreous body during surgery. While it is common for lens cortical fiber debris to leak into the vitreous humour during cataract extraction, the extent to which the vitreous humour is altered post-surgery is unknown. The current study examines the integrity of the vitreous humour of pseudophakic and phakic human donor eyes by comparing the proteome, the viscosity and the size distribution of macromolecules in different regions of the vitreous humour from human pseudophakic and phakic donor eyes. Major differences between the proteomes of anterior and posterior vitreous humour were observed in phakic and pseudophakic donor eyes. Seventeen spots identified as complete, modified or cleaved forms of alphaA-, alphaB-, betaA4-, betaB2, and gammaS-crystallins were present in the anterior vitreous humour of all pseudophakic eyes studied. Crystallins were not detected in the posterior vitreous humour of the pseudophakic eye or the vitreous humour of the phakic eye. Significant alterations in abundance and/or modification of transthyretin, alpha antitrypsin, and retinoic acid binding protein were observed in all locations of pseudophakic vitreous humour as compared to phakic samples. In addition, a significant decrease in the number and intensity of protein spots was observed for the posterior vitreous humour of pseudophakic eyes when compared to posterior vitreous humour of phakic eyes. Proteins which were affected include antioxidant proteins and enzymes such as carbonic anhydrase and trisephosphate isomerase. A reversal of the viscosity gradient, anterior to posterior, in the vitreous humour of pseudophakic eyes was observed concomitant with alterations in the distribution of 50 nm particles. These particles are likely primarily composed of hyaluronan. While varying degrees of vitreous degradation may have existed prior to surgery and may have contributed to the cataract formation, in no case did the phakic donor eyes exhibit the same alterations in the vitreous humour proteome, viscosity or particle sizes as did the pseudophakic donor eyes. The examination of phakic/pseudophakic donor eye pairs confirmed that the vitreous humour proteome and structural integrity were very similar in the matched phakic donor eye to eyes from donors with no history of cataract. Even though the number of samples for this study was limited, the observed changes support the hypothesis that alterations in the vitreous humour proteome occur in psuedophakic eyes with concurrent alterations in the structure of the vitreous humor. These modifications of the microenvironment of the retina may contribute to the development of retinal complications following cataract surgery.

Pleuropulmonary blastoma and ovarian teratoma.

We report a patient with pleuropulmonary blastoma who had a benign teratoma as a second primary tumor. The radiology, clinical course, and the biological importance of this rare neoplasm are discussed.

Intramural anomalous left coronary artery from the right sinus of Valsalva supported with venoarterial extracorporeal membrane oxygenation.

We report the case of a 14-month-old girl with a wide complex dysrhythmia and cardiogenic shock due to abnormal coronary anatomy. She was kept alive for 20 days by full cardiocirculatory support, using venoarterial extracorporeal membrane oxygenation (VA ECMO). While she was on VA ECMO, a diagnosis was made of extensive myocardial infarction and an anomalous left main coronary artery. The patient was listed for heart transplantation and received a donor heart 20 days after beginning VA ECMO. We discuss the unusual presentation and course of the coronary arteries and the use of VA ECMO to support this patient before heart transplantation.

Prolonged acceptance of concordant and discordant xenografts with combined CD40 and CD28 pathway blockade.

BACKGROUND: The prompt and vigorous immune response to xenogenic tissue remains a significant barrier to clinical xenotransplantation. Simultaneous blockade of the CD28 and CD40 costimulatory pathways has been shown to dramatically inhibit the immune response to alloantigen. METHODS: . In this study, we investigated the ability of simultaneous blockade of the CD28 and CD40 pathways to inhibit the immune response to xenoantigen in the rat-to-mouse and pig-to-mouse models. RESULTS: Simultaneous blockade of the CD28 and CD40 pathways produced marked inhibition of the cellular response to xenoantigen in vivo and produced long-term acceptance of xenogeneic cardiac and skin grafts (rat-to-mouse), and markedly suppressed an evoked antibody response to xenoantigen. In addition, this strategy significantly prolonged the survival of pig skin on recipient mice. CONCLUSIONS: Long-term hyporesponsiveness to xenoantigen across both a concordant and discordant species barrier, measured by the stringent criterion of skin grafting, can be achieved using a noncytoablative treatment regimen.

Medium-term results of pediatric patients undergoing orthotopic heart transplantation.

To establish the medium-term results of our transplant population, we retrospectively reviewed the charts of 51 consecutive patients who underwent orthotopic heart transplantation between July 1988 and April 1995. These patients comprised two groups: group A consists of 26 patients (age 6 days to 16.4 years, median 1.4 years) with no previous heart surgery, and group B consists of 25 patients (ages 0.1 to 14.3 years, median 8.3 years), all of whom had heart surgery before undergoing transplantation. There was no difference between these groups in early or late survival rates, and neither age at transplantation nor sex was an indicator of survival. There have been 14 deaths, six early (before hospital discharge) and eight late. Early deaths have predominantly been attributed to long-term ventilation and hemodynamic instability before transplantation, and late deaths to graft coronary artery disease (n = 4), acute coronary vasculitis (n = 3), and acute cellular rejection (n = 1). Although infection has resulted in significant morbidity (57 hospital admissions), there have been no late deaths resulting from infection. Sepsis accounts for four early deaths in chronically ill patients. Orthotopic heart transplantation in the pediatric patient with and without previous heart surgery is a viable option for those with end-stage heart disease and those in whom other surgical options carry a prohibitively high mortality rate.

Initiatives to build a competitive healthcare system: integrating service redesign and clinical pathways.

In this article, the authors describe how two separate initiatives (the redesign of hospital services and the development and implementation of clinical pathways) were integrated at an academic medical center. The lessons learned in integrating projects that were not conceived at the same time and in developing multidisciplinary teams to produce new case management tools may be used by clinicians and managers elsewhere. The service redesign project developed a role for senior, experienced nurses with clinical expertise and patient management skills to manage the care of groups of similar patients, focusing on patient outcomes. The clinical pathway project developed diagnostic related groups-based clinical pathways. The steps involved in clinical pathway development-stakeholder cooperation building, initiation of data collection tools, data analysis, implementation of the role of the expert nurse in "championing" the pathway, and evaluation of the effects of pathways-are discussed.

Work redesign: making it a reality.

Everyone involved in work redesign must recognize the need to plan for change, thus breaking the myth that new job descriptions primarily affect only the new worker. As part of redesign, specific questions regarding task analysis and job bundling need to be asked. Implementation of a new work design in a medical center applying these principles is described.

Project management. Lessons learned from introducing a multitask environmental worker program.

During a 13-month successful introduction of unit-based, multiskilled environmental workers at an academic medical center, responsibility for environmental support services migrated from centrally managed departments to more than 30 patient-care units. The authors discuss six project management lessons that may be used by clinicians and managers as they participate in service reorganization. Points related to the identification of committed leaders, exploration of barriers, planning, continuous training, negotiation, and communication are presented. Professional nurses who demonstrate their ability to work with these types of service innovations while clearly identifying clinical aspects best left unincorporated in such job descriptions will be in demand as participants in redesign efforts.

Analysis of allogeneic and syngeneic rat heart transplants using 23Na magnetic resonance spectroscopy.

This study defines the total sodium-23 magnetic resonance spectroscopy (23Na MRS) signal from in vivo heterotopic rat heart transplants in the early post-transplant period and examines the utility of this noninvasive method for monitoring allograft rejection. Measurements were performed at 4.7 T. Syngeneic (n = 6) and allogeneic (n = 6) donor hearts were transplanted into the neck of recipient rats. There were 27 MRS observations between days 0 and 29 post-transplant. Heart grafts were excised at various intervals post-transplant for histologic examination. Allogeneic heart grafts rejected between days 4 and 5 post-transplant while syngeneic grafts continued to beat. All hearts showed ischemic damage. Allogeneic hearts showed cellular rejection by Day 1. 23Na MRS showed a steady elevation in signal in the 3 days prior to rejection and a sharp rise after rejection. 23Na MRS accurately identified full rejection and was also sensitive to the rejection process.

Long-term acceptance of skin and cardiac allografts after blocking CD40 and CD28 pathways.

The receptor-ligand pairs CD28-B7 and CD40-gp39 are essential for the initiation and amplification of T-cell-dependent immune responses. CD28-B7 interactions provide 'second signals' necessary for optimal T-cell activation and IL-2 production, whereas CD40-gp39 signals co-stimulate B-cell, macrophage, endothelial cell and T-cell activation. Nonetheless, blockade of either of these pathways alone is not sufficient to permit engraftment of highly immunogenic allografts. Here we report that simultaneous but not independent blockade of the CD28 and CD40 pathways effectively aborts T-cell clonal expansion in vitro and in vivo, promotes long-term survival of fully allogeneic skin grafts, and inhibits the development of chronic vascular rejection of primarily vascularized cardiac allografts. The requirement for simultaneous blockade of these pathways for effective inhibition of alloimmunity indicates that, although they are interrelated, the CD28 and CD40 pathways are critical independent regulators of T-cell-dependent immune responses.

CTLA4-Ig plus bone marrow induces long-term allograft survival and donor specific unresponsiveness in the murine model. Evidence for hematopoietic chimerism.

Allograft rejection is dependent on T cell activation, which requires both the engagement of the T cell receptor by antigen in the context of the MHC molecules and costimulatory signals delivered by cell surface molecules such as B7-CD28/CTLA4 pathway. CTLA4-Ig is a fusion protein that blocks this pathway and has previously been shown to prolong both allograft and xenograft survival. The current study demonstrates markedly prolonged murine cardiac allograft survival and specific prolongation of secondary skin grafts using a combination of CTLA4-Ig plus donor bone marrow. A role for hematopoietic chimerism in the establishment of CTLA4-Ig-induced transplantation tolerance was investigated using reverse transcriptase polymerase chain reaction analysis of recipient tissues. Expression of donor-specific MHC class II transcripts in both peripheral and lymphoid tissues was demonstrated at greater than 200 days after transplant. To investigate the functional significance of this observation, heart donors, and donor bone marrow were irradiated before transplantation in CTLA4-Ig-treated recipients. A reduction in allograft survival was associated with irradiation of both the donor heart and the bone marrow. These results suggest that there may be a donor-derived radiosensitive element that enhances allograft survival in this model. Reverse transcriptase polymerase chain reaction analysis of allografts of tolerant and control animals at days 5, 8, and 12 after transplantation failed to demonstrate a dramatic difference in the expression of interleukin (IL)-2, IL-4, IL-10, and interferon-gamma message. Cytotoxicity effector transcripts were largely intact in CTLA4-Ig + bone marrow-treated recipients as they showed no decrease in intragraft granzyme, perforin, Fas, or Fas ligand transcripts during thr first 8 days after transplant. These results imply that complex mechanisms may be important for the induction and maintenance of transplantation tolerance in the CTLA4-Ig plus bone marrow murine cardiac allograft model.

Isolated magnesium malabsorption in a 10-year-old boy.

Isolated magnesium malabsorption (congenital hypomagnesemia) has been reported in approximately 30 patients worldwide. Patients typically present by 6 months of age with convulsions and diarrhea. We report an unusual case of isolated magnesium malabsorption in an older boy with no diarrhea.

Regulatory requirements and the multi-task worker.

This paper describes a framework for compliance the regulatory agency requirements and internal service standards in response to service decentralization and institution of a multi-task environmental worker role. Initiation and maintenance of the compliance system and the coordination of institutionally specific service standards are described. Five keys for success are detailed.

Massive ovarian edema in the pediatric patient: a rare solid tumor.

Solid ovarian masses in children are considered malignant unit proven otherwise. The authors report two cases of an unusual, benign, solid ovarian tumor found during ultrasound examination for evaluation of acute abdominal pain. Both patients were found to have a torsed nonviable ovary at the time of laparotomy. Patient 1 was a premenarcheal 10 year old who had undergone a lengthy evaluation for intermittent chronic abdominal pain. The ultrasound examination showed a 9- x 5-cm ovarian mass. Patient 2 was a virilized menarcheal 11 year old with a very large tumor (10 x 7 x 16 cm). The final pathology for both tumors was massive ovarian edema--a rare, stromal, virilizing tumor caused by chronic venous and lymphatic obstruction. Contralateral oophoropexy is a controversial treatment for the remaining ovary. A review of the literature regarding this uncommon tumor is provided.

Sudden infant death syndrome prevention and an understanding of selected clinical issues.

The etiology and prevention of sudden infant death syndrome (SIDS) are among the more frustrating topics in pediatrics. This article addresses several clinically relevant issues, including the relationships between apnea and SIDS, the nature of the "terminal event," effectiveness of home monitoring, the role of gastroesophageal reflux in apparent life-threatening events, and the association between the prone sleeping position and SIDS. This article is intended to provide the clinician with an awareness of the issues and the scientific basis needed to understand their contribution to SIDS.

Introducing a two-way wireless communication system.

Three medical/surgical units in a Midwestern medical center introduced a two-way wireless communication system to test its effect on environmental noise, staff communication, timeliness of response to patient requests, nurse fatigue and job satisfaction. Data were collected through focus groups, surveys, pedometer studies and work sampling. Results provide for nurse managers the first objective evaluation of the potential of this new device and a framework for designing other nursing evaluations of the effects of a new technology.

Transplantation tolerance induced by CTLA4-Ig.

The rejection of the transplanted allograft is dependent on T cell activation, which requires T cell receptor engagement by antigen and costimulatory signals delivered by T cell surface molecules such as CD28. CTLA4-Ig is a fusion protein that has previously been shown to block the CD28-mediated costimulatory signal and inhibit immune responses in vitro and in vivo. In this report we show that treatment of the C3H/He recipient of a BALB/c vascularized cardiac allograft with a 12-day course of CTLA4-Ig produced indefinite graft survival (> 100 days) in the majority of recipients. In addition, these recipients demonstrated donor-specific transplantation tolerance when tested with donor-specific (BALB/c) and third-party (C57BL/10) skin grafts. These results demonstrate that CTLA4-Ig can induce transplantation tolerance in the adult murine cardiac allograft model.

The impact of patient point-of-view pharmacy delivery on labor and quality.

A 37-bed surgical unit in a Midwestern Medical Center was the site of 30 day trials of three methods of medication delivery: (a) traditional medication cart, (b) patient point-of-view (PPOV1) delivery of regularly ordered medication by a pharmacy technician to the nurse server once a day, and (c) patient point-of-view (PPOV2) delivery of all medications (including stats and i.v.s) to the nurse server hourly between 0700 and 2300 hours. The purpose of this trial was to determine the effects of two alternative pharmacy delivery strategies on labor costs, use of professional nurses' time, and ten quality indicators related to medication administration.

Malignant risk in juvenile polyposis coli: increasing documentation in the pediatric age group.

The presence of juvenile polyps with resulting bleeding and abdominal pain has traditionally been considered a benign, self-limiting process which would resolve with age. The dictum that these polyps were usually solitary, were found predominantly in the rectosigmoid area, and were without malignant potential has been reconsidered in recent years with the increased use of colonoscopy. Several case reports in both adults and children have documented the presence of adenomatous changes in this syndrome. We report 3 cases of children, ages 3, 11, and 11 who were found to have adenomatous polyps in the midst of fields of juvenile polyps on evaluation for rectal bleeding. All three were treated definitively with endorectal pull-through. Two of these patients had atypia on histological evaluation, one of which was severe. We recommend a more aggressive approach to patients found to have multiple juvenile polyps on barium enema, including colonoscopic biopsies at several sites to determine the presence of adenomatous changes, with colectomy and endorectal pull-through should these be found.

Avian model for 13-cis-retinoic acid embryopathy: morphological characterization of ventricular septal defects.

In developing an avian model for 13-cis-retinoic acid (13cisRA) embryopathy, we found 13cisRA induced cardiovascular defects, especially Type I ventricular septal defects (VSDs) (Hart et al.: Teratology 41:463-472, '90). As the first step of investigating possible mechanisms, we have examined the light microscopic morphology of RA-induced cardiovascular defects in chick embryos. Fertilized eggs were injected via yolk sac with 150 micrograms 13cisRA in dimethylsulfoxide (DMSO), DMSO or mock injection on embryonic day 5 (E5). On E6, E7, or E8, surviving embryos were sacrificed and fixed in 10% formalin. Thoracic blocks were exised, embedded in paraffin and serially sectioned through the heart, base to apex. Slides were stained, screened for tissue orientation, then coded and evaluated without knowledge of treatment group. Examination of serial sections permitted qualitative evaluation of conotruncal ridge volume, mesenchymal organization, necrosis and extent of fusion. Extent of fusion was the only parameter influenced by 13cisRA treatment. On E6, ridge fusion was incomplete in all groups at comparable levels. On E7, ridge fusion in 13cisRA-treated embryos had not progressed as far proximally as in controls. By E8, there was a significant difference in the extent of fusion between 13cisRA-treated and non-RA-treated groups. We conclude 13cisRA-induced VSDs resulted from defective conotruncal ridge fusion and that the fusion defects did not result from decreased tissue volume, altered mesenchymal organization or increased necrosis.