Optic nerve degeneration caused by supraophthalmic carotid artery infusion with cisplatin and ACNU. Case report

A 28-year-old woman with a left frontoparietal anaplastic astrocytoma was treated postoperatively with a combination of cisplatin and 1-(4-amino-2-methylpyrimidine-5-yl) methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride (ACNU). The drugs were infused via the left supraophthalmic internal carotid artery in an attempt to avoid ocular toxicity. The patient subsequently developed blindness in the left eye and a right temporal hemianopsia from marked degeneration of the left optic nerve and tract. It is apparent that the placement of a catheter into the supraophthalmic carotid artery does not exclude visual complications.     

The NK1 receptor and its participation in the synergistic enhancement of corneal epithelial migration by substance P and insulin-like growth factor-1

1. We have previously shown that substance P (SP) and insulin-like growth factor-1 (IGF-1) act synergistically to enhance the migration of rabbit corneal epithelial cells in an organ culture model. The present study was designed to identify the epithelial cell SP receptor that participates in this synergistic effect.
2. Rabbit corneal blocks were incubated for 24 h, then the length of the path of epithelial migration was measured. Reagents tried in the TC-199 culture medium, in the presence or absence of IGF-1, were: SP, agonists of tachykinin receptors NK₁, NK₂ or NK₃ and antagonists of tachykinin receptors NK₁ or NK₂.
3. The binding characteristics of SP receptors were examined in rabbit cultured corneal epithelial cells by binding assays with [¹²⁵I]-SP in the presence or absence of excess unlabelled SP or ligands of NK₁, NK₂ or NK₃ receptors.
4. As was demonstrated previously, SP and IGF-1 stimulated epithelial migration when they were added to the culture medium together, but individually they had no effect. NK₁ agonists had the same synergistic effect with IGF-1 as did SP, but the NK₂ and NK₃ agonists did not. Furthermore, the NK₁ antagonist abolished the synergistic effect of SP and IGF-1, but the NK₂ antagonist had no effect.
5. SP bound specifically to rabbit cultured corneal epithelial cells. The binding affinity was 0.44 nM and there were 2.43×10⁴ binding sites per cell. The NK₁ ligand competed, in a dose-dependent fashion, with the binding of SP to corneal epithelial cells, but neither the NK₂ nor NK₃ ligand affected binding.
6. We conclude that the SP receptor in rabbit corneal epithelial cells is NK₁ and that this receptor participates in the synergistic enhancement of corneal epithelial migration by SP and IGF-1. The precise mechanism(s) of this interaction requires more study. These findings imply that both neural and humoral factors are essential for the maintenance and healing of corneal epithelium.

     

Two cases of methicillin-resistant <Emphasis Type="Italic">Staphylococcus aureus</Emphasis> keratitis after Epi-LASIK

Background  We describe two severe cases of methicillin-resistant Staphylococcus aureus (MRSA) keratitis following Epi-LASIK surgery. Cases  One patient was a 23-year-old man who underwent Epi-LASIK surgery in both eyes. He developed an infectious corneal ulcer in one eye 2 days after surgery and was referred to us 7 days post-surgery with corneal perforation, for which we performed therapeutic penetrating keratoplasty. The other patient was a 32-year-old man who developed infectious keratitis in one eye 4 days after bilateral Epi-LASIK and was referred to us 2 days later. Observations  Microbial testing revealed MRSA infection as the cause of the keratitis in both patients which was successfully treated with vancomycin eyedrops. Conclusion  Infectious keratitis after refractive surgery is uncommon; it is important to diagnose this condition, identify the causative agent, and initiate treatment with appropriate antibiotics as soon as possible.     

Characterization of insulin-like growth factor-1 receptors in rabbit corneal epithelial cells

Substance P (SP) and insulin-like growth factor-1 (IGF-1) synergistically facilitate corneal epithelial wound healing in vitro and in vivo. This synergism is mediated through the NK-1 receptors for SP, and IGF-1 does not modulate the binding affinity of NK-1 receptors. To clarify the effect of SP on the binding characteristics of IGF-1 receptors, the binding affinity and number of binding sites for IGF-1 in rabbit corneal epithelial cells were studied using a binding assay for(125)I-IGF-1. The binding affinity and number of binding sites for IGF-1 were determined by Scatchard plot analysis. Cultured rabbit corneal epithelial cells bound specifically to IGF-1. For IGF-1 in corneal epithelial cells, the binding affinity was 4 n m and the number of binding sites was 1x10(5)binding sites cell(-1). Although IGF-2 and insulin also bind to IGF-1 receptors, their affinities were, respectively, eight- and 300-fold lower than that of IGF-1. IGF-1 and IGF-2 stimulated corneal epithelial migration in the presence of SP, but insulin did not. Pretreatment of the corneal epithelial cells with SP (2x10(-5)m) failed to change the binding affinity or number of binding sites for IGF-1. These results demonstrated that corneal epithelial cells possess specific receptors for IGF-1. The synergistic effect of SP and IGF-1 on corneal epithelial wound healing does not result from regulation at the receptor level.     

Role of heparan sulfate proteoglycan (syndecan-1) on the renal epithelial cells during calcium oxalate monohydrate crystal attachment

We have reported that heparan sulfate (HS)/heparan sulfate proteoglycan (HSPG, syndecan-1) expression significantly increased in the rat kidney during calcium oxalate (CaOx) nephrolithiasis. Although the exact role of syndecan still remains unclear, HS/syndecan-1 is thought to have some important role in the CaOx crystal formation. Mardin-Darby canine kidney (MDCK) cells are most commonly used in kidney stone research. It was reported that MDCK cells do not express syndecan-1. In the present study, we established a novel MDCK cell line (KIC-synd-1) that expressed the human syndecan-1 gene. In this cell line, we confirmed stable expression of both sndecan-1 gene and core protein. Immunohistochemical study revealed positive staining of syndecan-1 monoclonal antibody in the basolateral and cytosolic area of the KIC-synd-1 cells. We also investigated the composition of glycosaminoglycans (GAGs) side chains in MDCK cells and KIC-synd-1 cells by using high-performance liquid chromatography (HPLC). Four types of HS chains were identified in both cells as follows; delta diHS-NS, delta diHS-6S, delta diHS-diS1, delta diHS-diS2. Increased production of delta diHS-NS and delta diHS-diS2 were shown in KIC-synd-1 cells compared with production in MDCK cells (p < 0.05). In contrast, only a small amount of delta diHS-6S and delta diHS-diS1 was contained in both cell lines. Total amount of HS was significantly increased in the KIC-synd-1 cells compare with that in the wild type MDCK cells (p < 0.05). Scanning electron microscopy revealed no significant difference between cell surface of wild type MDCK cells and that of KIC-synd-1 cells in normal conditions. However, calcium oxalate crystal attachment was apparently decreased in the KIC-synd-1 cells. These results suggested that cell surface HS/syndecan-1 has preventive role for calcium oxalate nephrolithiasis via creation of a charge barrier against COM crystal attachment.     

Cell-matrix and cell-cell interactions during corneal epithelial wound healing

The corneal epithelium serves as a barrier and contributes to the maintenance of corneal transparency and rigidity. In most instances, corneal epithelial defects caused by simple injury are resurfaced promptly. However, in individuals with certain clinical conditions, such as herpes simplex virus infection, neurotrophic keratopathy or diabetic keratopathy, corneal epithelial defects persist and do not respond to conventional treatment regimens because of delayed epithelial wound healing. After the corneal epithelium is removed by injury, the remaining epithelial cells migrate over the denuded surface of the cornea in a manner that is dependent both on the interaction of the cells with the underlying substrate and on cell-cell adhesion. In this review, we describe the specific roles of cell-matrix and cell-cell interactions during the course of corneal epithelial wound healing. The clinical implications of the basic research findings are also discussed.     

Metacarpal bone mineral density,body mass index and lifestyle among postmenopausal Japanese women: relationship of body mass index,physical activity,calcium intake,alcohol and smoking to bone mineral density: the Hizen-Oshima study

The present study was designed to investigate the influence of modifiable risk factors (body weight and lifestyle) for bone loss on bone mineral density (BMD). We examined age-specific changes in metacarpal BMD, and its associations with body mass index and lifestyle among 532 community-dwelling postmenopausal Japanese women. Measurements of the second metacarpal BMD were obtained from the hand radiographs using computer-assisted radiographic absorptiometry. Body height and weight were measured, and body mass index (BMI) was calculated. Physical activity index was calculated using validated questionnaire. Daily calcium intake and amount of ingested alcohol were estimated by semiquantitative food frequency questionnaire. Current smoking status was obtained by questionnaire. Metacarpal BMD decreased significantly with increasing age. Simple correlation analysis indicated that metacarpal BMD correlated significantly with BMI and physical activity index. On the other hand, metacarpal BMD did not correlate with calcium intake and alcohol drinking. Metacarpal BMD in current smokers was not different from that in nonsmokers. Multiple regression analysis showed that increasing age was associated with decreased metacarpal BMD and greater BMI increased metacarpal BMD. However, physical activity, calcium intake, alcohol drinking and current smoking were not significant determinants of metacarpal BMD. Our findings suggest that maintenance of adequate body mass (prevention for leanness) is important for prevention of postmenopausal bone loss.     

Idiopathic osteonecrosis of the first metatarsal sesamoid

Four patients with histologically confirmed osteonecrosis of the first metatarsal sesamoid are presented. No patient was an athlete, nor recalled any noticeable trauma or significant stress as having occurred to the feet. No foot deformities or joint malalignments were found. Excellent results were obtained by excision of the affected sesamoid in all patients, after follow-up periods of 1 to 12 years. Microscopic findings were compatible with those seen in idiopathic osteonecrosis of the femoral head.