SAA1 polymorphisms are associated with variation in antiangiogenic and tumor-suppressive activities in nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) is a cancer that occurs in high frequency in Southern China. A previous functional complementation approach and the subsequent cDNA microarray analysis have identified that serum amyloid A1 (SAA1) is an NPC candidate tumor suppressor gene. SAA1 belongs to a family of acute-phase proteins that are encoded by five polymorphic coding alleles. The SAA1 genotyping results showed that only three SAA1 isoforms (SAA1.1, 1.3 and 1.5) were observed in both Hong Kong NPC patients and healthy individuals. This study aims to determine the functional role of SAA1 polymorphisms in tumor progression and to investigate the relationship between SAA1 polymorphisms and NPC risk. Indeed, we have shown that restoration of SAA1.1 and 1.3 in the SAA1-deficient NPC cell lines could suppress tumor formation and angiogenesis in vitro and in vivo. The secreted SAA1.1 and SAA1.3 proteins can block cell adhesion and induce apoptosis in the vascular endothelial cells. In contrast, the SAA1.5 cannot induce apoptosis or inhibit angiogenesis because of its weaker binding affinity to αVß3 integrin. This can explain why SAA1.5 has no tumor-suppressive effects. Furthermore, the NPC tumors with this particular SAA1.5/1.5 genotype showed higher levels of SAA1 gene expression, and SAA1.1 and 1.3 alleles were preferentially inactivated in tumor tissues that were examined. These findings further strengthen the conclusion for the defective function of SAA1.5 in suppression of tumor formation and angiogenesis. Interestingly, the frequency of the SAA1.5/1.5 genotype in NPC patients was ~2-fold higher than in the healthy individuals (P=0.00128, odds ratio=2.28), which indicates that this SAA1 genotype is significantly associated with a higher NPC risk. Collectively, this homozygous SAA1.5/1.5 genotype appears to be a recessive susceptibility gene, which has lost the antiangiogenic function, whereas SAA1.1 and SAA1.3 are the dominant alleles of the tumor suppressor phenotype.

A missense mutation in a highly conserved region of CASQ2 is associated with autosomal recessive catecholamine-induced polymorphic ventricular tachycardia in Bedouin families from Israel.

Catecholamine-induced polymorphic ventricular tachycardia (PVT) is characterized by episodes of syncope, seizures, or sudden death, in response to physical activity or emotional stress. Two modes of inheritance have been described: autosomal dominant and autosomal recessive. Mutations in the ryanodine receptor 2 gene (RYR2), which encodes a cardiac sarcoplasmic reticulum (SR) Ca(2+)-release channel, were recently shown to cause the autosomal dominant form of the disease. In the present report, we describe a missense mutation in a highly conserved region of the calsequestrin 2 gene (CASQ2) as the potential cause of the autosomal recessive form. The CASQ2 protein serves as the major Ca(2+) reservoir within the SR of cardiac myocytes and is part of a protein complex that contains the ryanodine receptor. The mutation, which is in full segregation in seven Bedouin families affected by the disorder, converts a negatively charged aspartic acid into a positively charged histidine, in a highly negatively charged domain, and is likely to exert its deleterious effect by disrupting Ca(2+) binding.

Acute effect of latanoprost on pulsatile ocular blood flow in normal eyes.

PURPOSE: To determine the effect of an acute dose of 0.005% latanoprost on intraocular pressure and pulsatile ocular blood flow in normal eyes. METHODS: Nineteen volunteers received a single dose (two drops) of latanoprost 0.005% in one eye and placebo in the fellow control eye, randomized and masked to the observer. Intraocular pressure, perfusion pressure, pulsatile ocular blood flow, and systemic circulatory parameters were measured before and 8 hours after dosing. RESULTS: The mean (+/- SE) intraocular pressure, perfusion pressure, and pulsatile ocular blood flow before treatment were 17 +/- 1 mm Hg, 46 +/- 3 mm Hg, and 13 +/- 1 microl per second, respectively, in both the treated and control eyes. The mean intraocular pressure reduction was 4.9 and 2.1 mm Hg (28% and 12%) in the treated and fellow eye, respectively. The mean perfusion pressure increase was 5.6 and 2.8 mm Hg (12% and 6%) in the treated and fellow eye, respectively. The mean pulsatile ocular blood flow increase was 2.7 and 0.2 microl per second (20% and 1%) in the treated and fellow eye, respectively. The treated eye change in pulsatile ocular blood flow was not correlated to the change in perfusion pressure. Simultaneous reduction of intraocular pressure and increase or no significant change in pulsatile ocular blood flow occurred in 15 of 19 (79%) of the treated eyes. The systemic blood pressure and pulse rates remained in normal ranges over the 8-hour period. CONCLUSION: In this study, topical latanoprost significantly reduces intraocular pressure and increases ocular blood flow in normal eyes 8 hours after dosing. These effects of latanoprost may be beneficial in the management of glaucoma patients.

Laser in situ keratomileusis to correct hyperopic shift after radial keratotomy.

PURPOSE: To assess the safety and efficacy of excimer laser in situ keratomileusis (LASIK) to correct hyperopic shift following radial keratotomy (RK). SETTING: Ophthalmic Health Center, Tel Aviv, Israel. METHODS: The study comprised 15 eyes of 12 patients who had uneventful RK and subsequently developed a hyperopic shift. Laser in situ keratomileusis was performed using the Chiron Automated Corneal Shaper and the Nidek EC-5000 excimer laser with 5.5 mm central and 7.5 mm peripheral ablation zones. The corneal flap was 160 microm in thickness and 8.5 mm in diameter. The refractive correction corresponded to the patients' refractive errors. RESULTS: The mean time after RK was 10.46 years +/- 2.21 (SD) and the mean follow-up after LASIK, 7.3 months (range 1 to 42 months). The mean spherical equivalent refraction was corrected from +3.08 +/- 1.02 diopters (D) to -0.16 +/- 0.73 D after LASIK. At the last examination, 12 eyes (80%) had a refractive error within +/-1.00 D of emmetropia and an uncorrected visual acuity of 20/40 or better. No wound dehiscence, epithelial ingrowth, or other significant complication developed in any eye. CONCLUSIONS: Early postoperative results of the correction by LASIK of a hyperopic shift after RK are encouraging, but long-term studies of a larger population group are required to evaluate the method's clinical value.

Hyperhomocystinemia in patients with nonarteritic anterior ischemic optic neuropathy, central retinal artery occlusion, and central retinal vein occlusion.

OBJECTIVE: This study aimed to determine the prevalence of hyperhomocystinemia among patients with nonarteritic anterior ischemic optic neuropathy (NAION), central retinal artery occlusion (CRAO), or central retinal vein occlusion (CRVO). DESIGN: Retrospective, case-control study. PARTICIPANTS: The study cohort consisted of 74 consecutive patients with NAION, CRAO, or CRVO who were examined at the Retina or Neuro-ophthalmological Unit of the Tel-Aviv Sourasky Medical Center from 1998 through 1999. The control group consisted of 81 consecutive patients of similar gender and age with no history of these pathologic conditions. MAIN OUTCOME MEASURES: Plasma homocystine levels of all study participants were obtained. RESULTS: Eighteen of 40 patients (45%) with NAION and eight of 13 patients (61.5%) with CRAO had hyperhomocystinemia compared with three of 21 (14.3%) in the CRVO group (P < 0.001) and eight (9.8%) in the control group (P < 0.0001). Hypertension and ischemic heart disease were significantly more prevalent in the NAION patients with elevated plasma homocystine. CONCLUSIONS: Our findings suggest that hyperhomocystinemia is a risk factor for NAION and CRAO.

Laser in situ Keratomileusis Following Acanthamoeba Keratitis.

PURPOSE: Although data regarding reactivation of microbial corneal infections following LASIK is scarce, the use of excimer laser is known to be an efficient trigger for the reactivation of herpes simplex keratitis. With this in mind, the use of excimer laser, including LASIK, theoretically places the cornea at potential risk for reactivation of other microbial infections. Acanthamoeba keratitis is a severe, painful, sight-threatening infection most often associated with soft contact lens use. Treatment of Acanthamoeba keratitis is notoriously difficult, and despite prolonged administration of anti-protozoal agents such as polyhexamethylene, propamidine isethionate (Brolene), and neomycin, recurrence of the keratitis can occur. Postoperative reactivation following penetrating keratoplasty performed for visual rehabilitation in patients with previous Acanthamoeba keratitis has been documented, and LASIK, when performed on these patients, may raise concerns about the potential risk of reactivation of the infection. METHODS: We report the case of a myopic patient with previous Acanthamoeba keratitis and corneal scarring who underwent LASIK without preoperative anti-protozoal prophylaxis. RESULTS: During a 6-month follow-up period after LASIK, no recurrence of the infection was noted. CONCLUSION: In our patient who previously suffered from Acanthamoeba keratitis and underwent LASDX, no reactivation of the infection was seen. [J Refract Surg 2000;16(suppl):S251-S252].

[Clinico-anatomical evaluation of donor kidneys unsuitable for transplantation]. / Kliniko-anatomicheskaia otsenka donorskikh pochek, neprigodnykh dlia transplantatsii.

The authors conducted clinicoanatomical analysis of 112 donor kidneys which clinicians found to be unfit for transplantation. The procedure of preparing the donors in these cases did not differ from that commonly accepted. An essential moment was prolonged arterial hypotension (6.0 +/- 0.8 hours), in donors whose kidneys were used for transplantation it lasted 2.0 +/- 0.2 hours. Examination showed that in 90% of cases the kidneys were unfit because of congenital or acquired diseases. It is concluded that the existing clinical methods for appraising the fitness of donor kidneys are adequate.

[Means for decreasing the incidence of postoperative tubular necrosis in kidney transplants]. / Puti snizheniia chastoty posleoperatsionnykh kanal'tsevykh nekrozov pochechnykh transplantatov.

An analysis of the work on transplanting 264 cadaver kidneys has shown a considerable decrease of delayed functions of the transplants due to an adequate anti-ischemic defense in the donor's organism and during operation in the recipient's organism. An exact scheme of medicamentous management of the potential donors and the corresponding transfusion therapy during transplantation of the kidney has reduced the percentage of delayed functions in renal transplants from 54.4 to 25.8%.

[Plasma zinc content in patients with chronic renal insufficiency before and after kidney transplantation]. / Soderzhanie tsinka v plazme bol'nykh khronicheskoi pochechnoi nedostatochnost'iu do i posle transplantatsii pochki.

Zinc content in blood plasma was measured in patients with chronic renal failure (CRF) before and after kidney transplantation by atomic-absorption spectrophotometry. Plasma zinc was revealed to be lowered. However, routine intake of vitamin A by the patients led to an elevation in zinc content. Hemodialysis did not alter blood plasma zinc concentration. It was noted that during the postoperative period, the zinc level returned to normal. Patients with CRF show marked disturbances of taste sensitivity, which are manifested in the increased threshold of taste sensitivity and perversion of taste sensations.