Bilateral scleral pit associated with systemic sclerosis

PURPOSE: To describe a case of a bilateral scleral pit in a patient with systemic sclerosis. METHODS: Case report. RESULTS: A bilateral scleral pit with surrounding scleral ischemia overlying the pars plana was noted in a 72-year-old woman with known systemic sclerosis. CONCLUSIONS: Scleral pits should be added to the list of ocular findings associated with systemic sclerosis.     

Discovery and Development of LX7101, a Dual LIM-Kinase and ROCK Inhibitor for the Treatment of Glaucoma

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Tamoxifen: evidence by 32P-postlabeling and use of metabolic inhibitors for two distinct pathways leading to mouse hepatic DNA adduct formation and identification of 4-hydroxytamoxifen as a proximate metabolite

Exposure to pentachlorophenol (PCP) strongly intensifies theformation of mouse hepatic DNA adducts elicited by oral administrationof tamoxifen (TAM), as previously shown by ³²P-postlabeling.To explain this effect, PCP was proposed to interfere with thedetoxication by sulfate conjugation of an as yet unidentifiedhydroxylated proximate TAM metabolite. A comparison of the presentand earlier results shows that the hepatic TAM adduct patternin female ICR mice depended on the route of administration ofTAM (120 µmol/kg), with oral administration primarilyeliciting formation of more polar adducts (termed group I adducts),while after i.p. administration less polar adducts (group II)predominated over group I adducts by a factor of 17.5. All theseadducts were also formed in female Sprague–Dawley ratsafter i.p. dosing with TAM, but total adduct levels were 3.5-to 5-fold higher than in mice. After four daily i.p. treatments,TAM adducts accumulated in mouse liver DNA in a non-linear fashion.Adduct levels were 30–50 times lower in mouse kidney andlung than in liver. The phenolic metabolite 4-hydroxy TAM (120µimol/kg) exclusively led to formation of polar (groupI) hepatic adducts, and this process was stimulated 8-fold bycoadministration of PCP (75 µimol/kg). Co-administrationof PCP with the parent compound led to an 11-fold enhancementof group I adduct formation; simultaneously, levels of groupII adducts were suppressed 6-fold. Another inhibitor of sulfateconjugation, 2,6-dichloro-4-nitrophenol, unlike PCP, had noeffect on group I adducts, but it reduced group II adduct formation2.2-fold. The PCP metabolite 2,3,5,6-tetrachlorohydroquinone(75 µimol/kg) did not significantly affect any major TAMadduct, suggesting that PCP itself was the active compound.Similar to group II TAM adducts, the formation of hepatic safrole–DNAadducts was inhibited in female ICR mice by both sulfotransferaseinhibitors, consistent with the proposal that metabolic     

Measurements of disordered flows distal to subtotal vascular stenoses in the thoracic aortas of dogs.

Instantaneous blood velocity measurements employing a constant temperature hot film anemometer were obtained in the region distal to externally enforced, subtotal vascular stenoses in the descending thoracic aortas of anesthetized dogs. Our objectives were to determine alterations in velocity waveforms and energy spectra as the degree of stenosis was increased. We paid particular attention to distinguishing features of the flow which were characteristic of turbulence. Our results indicate that, for the vessels studied, disturbances in the velocity waveforms occur for very minor localized constrictions. The energy spectra follow certain similarity parameters within a restricted region of the distal velocity field. For severe stenoses relatively high levels of energy exist in frequency ranges which previously have been found to produce poststenotic dilation. The measurements suggest that velocity waveforms and energy spectra provide a very early clue to the existence of localized occlusive vascular disease in larger vessels and that, within a limited region distal to a stenosis, the degree of constriction may be estimated by similarity analysis of the energy spectra.     

Identification of sympathetic preganglionic neurons controlling the small intestine in hamsters using a recombinant herpes simplex virus type-1

Sympathetic preganglionic neurons (SPNs) may be organized topographically within the spinal cord for selective control of visceral organs. We used a recombinant herpes simplex virus type-1 (rHSV-1) to identify SPNs innervating the small intestine in hamsters. These SPNs were distributed bilaterally in the cord from the fifth thoracic spinal segment to the second lumbar segment, but predominantly in thoracic segments 5–10. They had morphology similar to that of renal and adrenal SPNs infected with HSV-1. The majority of intestinal SPNs were found in the intermediolateral cell column, with a few located in the lateral funiculus. The SPNs labelled following duodenal injection of rHSV-1 were in the same spinal segments as the SPNs labelled following jejunal or ileal injections, suggesting lack of a relation between target topography and the topographic organization of these neurons. In addition, intestinal SPNs were located in the same spinal segments, and autonomic nuclei as renal and adrenal SPNs suggesting that SPNs controlling the abdominal viscera are not organized viscerotopically for discrete control of different organs. © 1997 Elsevier Science B.V. All rights reserved.     

Amniotic membrane transplantation and fibrin glue in the management of corneal ulcers and perforations: a review of 33 cases

PURPOSE: To evaluate the efficacy of amniotic membrane in corneal ulcers refractive to conventional treatment and amniotic membrane with fibrin glue in corneal perforations. METHODS: Amniotic membrane transplantation (AMT) was performed in 33 eyes from 32 patients for corneal ulcers refractive to conventional treatment. Fourteen ulcers were perforated and received fibrin glue and amniotic membrane. Ulcers were divided into 3 groups: neurotrophic or exposure, autoimmune, and other etiology. RESULTS: Overall success was observed in 80% (27/33 eyes) of the cases, with success rates of 87.5% (14/16 eyes), 70% (7/10 eyes), 85.7% (6/7 eyes) in groups 1, 2, and 3, respectively. The ulcers healed in a mean time of 3.6 +/- 1.6 weeks and the follow-up was 14.8 +/- 9.9 months. Failure was noted in 6 eyes with severe neurotrophic keratitis, Stevens-Johnson syndrome, ocular cicatricial pemphigoid, and Acanthamoeba keratitis. Grafts with fibrin sealant showed a success rate of 92.9 % (13/14 eyes) compared to 73.7% (14/19 eyes) for amniotic grafts alone. In patients with severe limbal damage, a success rate of only 20% (1/5) was observed. CONCLUSIONS: AMT is a viable option in the treatment of nonhealing corneal ulcers of various depth and etiologies. Perforations up to 3 mm can be safely managed by fibrin glue and AMT. These techniques lead to rapid reconstruction of the corneal surface and can give a good final functional result or allow keratoplasty to be done in more favorable conditions.     

The role of novel DMEK graft shapes in facilitating intraoperative unscrolling

Graefe's Archive for Clinical and Experimental Ophthalmology - To evaluate whether the preparation of Descemet membrane endothelial keratoplasty (DMEK) grafts into various shapes affect their...     

FLT3 mutations in childhood acute lymphoblastic leukemia

Activating mutations of the FLT3 receptor tyrosine kinase are common in acute myelogenous leukemia (AML) but are rare in adult acute lymphoblastic leukemia (ALL). We have recently shown that FLT3 is highly expressed and often mutated in ALLs with rearrangement of the mixed lineage leukemia (MLL) gene on chromosome 11q23. Because hyperdiploid ALL samples also show high-level expression of FLT3, we searched for the presence of FLT3 mutations in leukemic blasts from 71 patients with ALL. The data show that approximately 25% (6 of 25) of hyperdiploid ALL samples possess FLT3 mutations, whereas only 1 of 29 TEL/AML1-rearranged samples harbored mutations (P =.04, Fisher exact test). Three mutations are novel in-frame deletions within a 7-amino acid region of the receptor juxtamembrane domain. Finally, 3 samples from patients whose disease would relapse harbored FLT3 mutations. These data suggest that patients with hyperdiploid or relapsed ALL might be considered candidates for therapy with newly described small-molecule FLT3 inhibitors.