Outcomes in children with nasolacrimal duct obstruction: Significance of persistent symptoms while stents are in place.

To evaluate the correlation between persistent symptoms while stents are in place and final outcome in children with nasolacrimal duct obstruction (NLDO). A retrospective observational case series, with medical record review that included indications for surgery, surgical procedure, presence of symptoms while stents were in place, and final outcome after stent removal. Twenty-eight children with NLDO had nasolacrimal duct stents placed in 42 eyes. Twenty-one of the 42 eyes (50%) had minimal or no signs or symptoms of NLDO while stents were in place, and 18 of 21 (86%) were symptom-free after stent removal. Twenty-one of the 42 eyes (50%) remained symptomatic while stents were in place. Eleven of these 21 eyes (52%) had good outcomes after stent removal. Ten (48%) of these patients had persistent symptoms after stent removal requiring further treatment. The prognosis for a good outcome is excellent if symptoms of NLDO resolve while stents are in place. The prognosis is poorer if symptoms of NLDO persist, but more than half of such patients still have good outcomes. Careful counseling of parents regarding these outcomes should be performed before considering additional interventions.     

Reduction of epidural fibrosis in lumbar surgery with Oxiplex adhesion barriers of carboxymethylcellulose and polyethylene oxide.

BACKGROUND CONTEXT: Postsurgical epidural adhesions and fibrosis after surgery for lumbar disc herniation are a consequence of normal wound healing. The presence of fibrosis renders reoperations risky, and in some patients fibrosis may lead to nerve root tethering. PURPOSE: One approach to minimizing the risk of developing epidural adhesions is to provide a barrier between the dural membrane and the healing connective tissues. The purpose of these studies was to evaluate such a barrier device. STUDY DESIGN/SETTING: In vivo investigation in an animal model at a university laboratory. PATIENT SAMPLE: Rabbit. OUTCOME MEASURES: Gross and histomorphic evaluation. METHODS: Barriers comprised of carboxymethylcellulose (CMC) and polyethylene oxide (PEO) (Oxiplex; FzioMed, Inc., San Luis Obispo, CA) were studied as devices to reduce epidural adhesion formation in rabbit laminotomy and laminectomy models. The barriers tested were either a gel alone (gel) or a gel covered with a film (gel/film combination). Two laminotomy or laminectomy sites (depending on the surgical method) were created in each rabbit at L4 and L6. One site was treated with a CMC/PEO gel, or CMC/PEO gel/film combination, and the other site served as a surgical control. Two surgical models that differed in the extent of adhesion formation at untreated injury sites and the method of injury generation were used. RESULTS: Model A, which did not incorporate dural abrasion, resulted in up to 40% adhesion-free laminectomy sites in controls. Model B, which did incorporate abrasion of the dural membrane, resulted in less than 10% adhesion-free laminotomy sites in controls. Compositions of CMC/PEO gels (2.5% to 10% PEO) and films (22.5% PEO) were tested in both models. Efficacy parameters included measuring the number of sites free of epidural fibrosis and reduction in the severity of fibrosis (adhesions). Both gels and gel/film combinations consistently reduced the frequency and the extent of epidural fibrosis in both models. Gels of CMC/PEO containing a higher content of PEO (10%) and a higher molecular weight of PEO (4.4 mD) were most effective in Model B and resulted in up to 84% laminotomy sites with minimal or no epidural fibrosis, whereas controls exhibited over 90% of the sites with epidural fibrosis. Histological evaluation of the surgical sites indicated that the reduction of epidural fibrosis was accompanied by normal bone healing. In addition, these experiments demonstrated that the gel/film combination provided no additional benefit to that obtained by the gel alone. CONCLUSIONS: Gels of CMC/PEO reduced epidural fibrosis and did not impair normal heal ing.     

Induction of Experimental Antiphospholipid Antibody Syndrome in PL/J Mice Following Immunization With β2GPI

PROBLEM: Immunization with β₂-glycoprotein I (β₂GPI) induces antiphospholipid antibodies (aPL) in normal mice and rabbits. Recently we reported early onset of autoimmunity in MRL/++ mice following immunization with β₂GPI. There is a close association between aPL with thrombosis, recurrent fetal loss, and intrauterine growth retardation. In this study we evaluated the effect of β₂GPI-induced aPL on pregnancy outcomes in an inbred strain of mice (PL/J). METHOD: Three groups of seven-week-old female PL/J mice (12 per group) were studied. Group A was immunized with β₂GPI and group B with ovalbumin; group C was not immunized. After two booster injections, the mice were tested for aPL, anti-DNA by ELISA, and for ANA by indirect immunofluorescence. Platelet count and pregnancy outcomes were studied at the age of 14 weeks. RESULTS: The aPL and anti-DNA levels were higher at 12 and 14 weeks in group A; the optical densities (OD) were 1.72±0.6 and 0.699±0.25 for group A, 0.091 ±0.040 and 0.230±0.47 for group B, and 0.0435±0.003 and 0.119±0.026 for group C (comparing group A with groups B and C combined, P<0.001). ANA titers rose in groups A and B by age, but they were significantly higher at 14 weeks in group A. The mean titers were 1/286, 1/90, and 1/16 for A, B, and C, respectively (P<0.001). The platelet counts were not significantly different among the three groups. The litter size was significantly smaller in group A, as evidenced by the numbers of viable fetuses among the mice that became pregnant in each group: 0.75, 2.45, and 5.5 in groups A, B, and C, respectively. Seven pregnant mice in group A had complete resorption, seven pregnant mice in group B showed focal (partial) resorption areas, and only one mouse in group C had complete resorption of the embryos, as shown by histopathological studies, although the fecundity rate was similar in the three groups. CONCLUSION: Our data suggest a pathogenic role for β₂GPI-induced aPL in the development of experimental models of APS in PL/J mice.     

Early onset of autoimmunity in MRL/++ mice following immunization with beta 2 glycoprotein I.

Antiphospholipid antibodies (aPL) are associated with thrombosis, thrombocytopenia and recurrent fetal loss in humans and in some animal models. Immunization with beta 2 glycoprotein I (beta 2GPI) induced aPL production in normal rabbits and mice. However, the association of these antibodies with disease manifestations remains controversial. To determine whether induction of aPL by beta 2GPI immunization in an autoimmune strain of mice (MRL/++) would result in acceleration of clinical and serological autoimmune disease manifestations, three groups of 8-week-old female mice were studied. One group was immunized with beta 2GPI, and one with ovalbumin (OVA); the third was not immunized. After two booster injections, sera were analysed for the presence of anticardiolipin (aCL) and anti-DNA by ELISA and anti-nuclear antibody (ANA) by immunofluorescence. Mice were studied for thrombocytopenia, proteinuria, fecundity rates, litter sizes and the development of central nervous system dysfunction. Elevated levels of aCL, anti-DNA and ANA were detected in all beta 2GPI-immunized, in three OVA-immunized, and in none of the unimmunized mice. The anti-DNA antibodies were inhibited by CL micelles, suggesting cross-reactivity between aCL and anti-DNA. Platelet counts, fecundity rates and litter size were reduced in beta 2GPI-immunized but not in OVA-immunized or unimmunized mice. None of the mice developed neurological dysfunction or significant proteinuria over a 10-week period post-immunization. These findings suggest that beta 2GPI immunization induces aPL in MRL/++ mice associated with accelerated autoimmune manifestations resembling the antiphospholipid syndrome.     

Intraluminal Radiation for Esophageal Cancer: A Howard University Technique

The objective of radiotherapeutic management in esophageal cancer is to accomplish maximum tumor sterilization with minimal normal tissue damage. This sincere effort is most often countered by the differential in tumor dose response vs normal tissue tolerance. Intraluminal isotope radiation, with its inherent advantage of rapid dose falloff, spares the lungs, the spinal cord, and other vital structures, yet yields adequately high doses to esophageal tumor. Though in existence since the turn of the century, the method of intracavitary radium bougie application dropped out of favor due to technical difficulties imposed by the size of the radium source and radiation exposure to the personnel involved. The authors describe a simple “iridium 192 afterloading intraluminal technique” that eliminates technical problems and reduces radiation exposure considerably.     

Severe, late-onset graft-versus-host disease in a liver transplant recipient documented by chimerism analysis

A 52-year-old liver transplant recipient presented 8 months after transplantation with oral thrush, then 3 days later with oral ulcers and a diffuse rash, and 5 days later with an acutely reduced white blood cell count, rash, fever, and diarrhea. Bone marrow biopsy revealed severe aplasia. Although graft-versus-host disease (GVHD) was considered, the late onset of these symptoms was felt to render this etiology unlikely because GVHD usually occurs 2 to 6 weeks after transplantation. All potentially myelosuppressive medications were discontinued, and the patient was treated with high doses of hematopoietic growth factors. Because his symptoms continued, chimerism analysis was performed, which indicated that 96% of the peripheral blood mononuclear cells were of liver-donor origin. Ultimately, the patient underwent an allogeneic peripheral blood hematopoietic progenitor cell transplant from a human leukocyte antigen-identical brother, but he died 5 days after transplantation of overwhelming Candida kruseii infection. To our knowledge, this is the first chimerism-analysis-documented case of severe acute GVHD presenting so late after liver transplantation. It is of note that the patient had no known risks for GVHD in that he was relatively young and shared only one major human leukocyte antigen with his donor. Consideration should be given to GVHD as a cause of bone marrow aplasia at any time after organ transplantation. Storage of cell pellets from all transplant recipients and donors is highly recommended to facilitate the diagnostic evaluation.     

Conformational change as one of the earliest alterations of tau in Alzheimer's disease

Paired helical filaments (PHFs) found in Alzheimer's disease (AD) are mainly comprised of an abnormal form of tau (PHF-tau) that has undergone several post-translational modifications. Previous studies have shown that the monoclonal antibody MCI identifies a distinct conformation of tau in AD. We have assessed the temporal and spatial occurrence of the tau conformation recognized by MC1, and found its appearance in hippocampal neurons vulnerable to neurofibrillary tangle (NFT) formation in Braak Stage I and II cases. Electron microscopy has clearly demonstrated that this conformation precedes the formation of PHF. MC1 immunoaffinity chromatography also has identified a nonfilamentous, soluble pool of this abnormal tau. ELISA and immunoblotting have shown that this material is indistinguishable from that found in NFTs. This soluble component has the ability to self-assemble into PHFs in a concentration-dependent manner. Because the conformational change recognized by MCI appears before the assembly of and is found in PHF, but is not present in the normal brain, we suggest that the formation of the MCI epitope is one of the earliest pathological alterations of tau in AD.