Effects of irrigation fluid temperature on choroidal circulation during vitrectomy.

PURPOSE: To investigate the effects of irrigation temperature on choroidal circulation during vitrectomy. METHODS: After anesthetized albino rabbits underwent closed vitrectomy, choroidal blood flow was monitored while the vitreous cavity was irrigated with solutions (BSS plus) of various temperatures (6-42 degrees C). Irrigation pressure was maintained at 15 mmHg. A non-contact Doppler laser flowmeter was used to measure choroidal blood flow. Temperature change at the retina and mid-vitreous was also measured during irrigation. RESULTS: Choroidal blood flow showed a downward peak when perfused at 34 degrees C. As irrigation temperatures deviated above or below 34 degrees C, the blood flow increased. However, when irrigation temperature was below 16 degrees C, the blood flow decreased as the temperature declined. The temperature at the retina was maintained at a relatively constant level when irrigation was between 30 degrees C and 40 degrees C. CONCLUSION: The choroid acts as a thermostat to minimize intraocular temperature fluctuations by changing its blood flow.     

Quantitative analysis of diabetic macular edema after scatter laser photocoagulation with the scanning retinal thickness analyzer

PURPOSE: To define the effect of scatter laser photocoagulation on foveal retinal thickness. METHODS: A commercial scanning retinal thickness analyzer was used to measure retinal thickness. The foveal retinal thickness was measured at the central area of the fundus (0.4 x 0.4 mm). The method was applied to 20 consecutive patients (mean age, 52.4 +/-16.9 years) with diabetic retinopathy. Measurements were performed before and 6 weeks after scatter photocoagulation. Patients were examined by fluorescein angiography and slit-lamp biomicroscopy to detect macular edema. RESULTS: Mean foveal thickness before scatter photocoagulation was 187+/-45 microm, increasing to 221+/-46 microm after the treatment (P = 0.0001). The foveal thickness increased in 12 eyes (60%). Laser treatment increased macular permeability in two eyes (10%). Biomicroscopic examination revealed central macular thickening in one eye (5%). Visual acuity was reduced in four eyes (20%). CONCLUSIONS: Our results suggest that subclinical macular edema occurs after scatter laser photocoagulation. The retinal thickness analyzer is a sensitive tool for early detection of macular edema after laser treatment, because increases in retinal thickness as small as 34 microm cannot be assessed by slit-lamp biomicroscopy.     

Inhibition of cardiac inward-rectifier K current by terodiline

The antispasmodic agent terodiline has cardiotoxic effects that include QT lengthening. To determine whether inhibition of inwardly-rectifying K⁺ current (I_K1) might be a factor in the cardiotoxicity, we measured I_K1 in guinea pig ventricular myocytes. Terodiline reduced outward I_K1 with an IC₅₀ of 7 μM; maximal reduction was 60% with 100–300 μM concentration. Inhibition was independent of current direction, and persisted after removal of the drug. Terodiline (3–5 μM) lengthened action potentials in guinea pig papillary muscles by ca. 10%, primarily by slowing phase 3 repolarization; higher concentrations abbreviated the plateau and markedly slowed late repolarization. Terodiline washout provoked an extra lengthening, consistent with persistent inhibition of I_K1 and rapid recovery of net inward plateau current. The results suggest that inhibition of I_K1 is a likely factor in the cardiotoxicity of the drug.     

Changes of enzyme activity levels in red blood cells in hemodialysis patients by recombinant human erythropoietin.

In a phase II clinical trial to test the ability of recombinant human erythropoietin (r-HuEPO) to reverse the anemia of patients undergoing hemodialysis, the changes of enzyme activity in red blood cells were evaluated in 5 hemodialysis anemic patients who were treated with r-HuEPO. Concerning the activity levels measured, the following conclusions are drawn. 1) HK, ALD, TPI, G6PD and 6PGD were statistically significantly increased at the time when the hematocrit has risen by 8% with the use of r-HuEPO. 2) The enzyme activity levels of PFK, GA3PD, MPGM, ENOL, PK, GR and ADA were higher than normal already before the r-HuEPO treatment. 3) The increases of HK and G6PD by r-HuEPO, as age dependent enzymes, may reflect the generation of young red blood cells. 4) In view of the fact that they are related to ATP production in the glycolysis cycle, we infer that increases of red blood cell enzymes by r-HuEPO may play at least some part in bringing a sensation of "well-being" to severely anemic patients undergoing hemodialysis.     

Programming a predictive rormula for angina and other risk factors in patients with cardiac diseases undergoing noncardiac operations

We programmed a formula which predicts the incidence of either myocardial infarction or cardiac death during the postoperative period. The original formula was proposed by Shah et al, based on their own data and analysis. The program is simple and is written in a language called Quick Basic. The use of this program is also simple. Such a program has improved the use of this analysis substantially. The program has been posted on to a few Computer network services as a free software.(Suwa K, Ogura S: Programming a predictive formula for angina and other risk factors in patients with cardiac diseases undergoing non-cardiac operations. J Anesth 6: 241–242, 1992)     

Determinations of oxalate in urine and plasma by capillary electrophoresis

PURPOSE: The determinations of oxalate in urine and plasma are important in the evaluation and treatment of patients with calcium oxalate nephrolithiasis. Although many analytical methods for determining oxalate have been developed, most of them need complicated sample preparation, and are expensive for routine examination. Especially for estimation of plasma oxalate, much more sensitive measurement is required because of the extremely low concentration. A simple and rapid assay for oxalate in urine and plasma by capillary electrophoresis has been described here, and utilized for assessment of renal oxalate clearance. In addition, simultaneous determination of urinary oxalate and citrate was developed. METHODS: A Waters Quanta 4000E system was used with a detection at 185 nm. Separation was obtained on a fused silica capillary, 60 cm long x 75 microns and 100 microns (i.d.) for urine and plasma samples respectively. Urine samples were diluted with 60 mM hydrochloric acid, and ultrafiltrates of plasma were acidified and diluted with 300 mM boric acid and 50 mM phosphoric acid. RESULTS: The intraassay coefficient variation was 2.7-4.0% for urinary oxalate, and 1.3-3.9% for citrate. The mean recovery ratio of 0.2 mM oxalate and 1.0 mM citrate added to 10 samples were 99.0% (92.6-107.4%) and 98.4% (91.2-103.9%), respectively. In the determination of plasma oxalate, the minimum detectable limit was 0.9 microM, the coefficient variation was 5.8-16.0%, and the recovery rate was 101.5% (87.8-125.6%). The plasma oxalate levels in 8 adult males were 2.39 +/- 1.46 microM (Mean +/- SD). Renal oxalate clearances with one hour method were 72.9 +/- 20.0 ml/min in 6 healthy controls and 83.2 +/- 27.8 ml/min in 8 stone formers. Oxalate/creatinine clearance ratios in each groups were 0.70 +/- 0.16 and 1.11 +/- 0.34 respectively. CONCLUSION: The simultaneous determination of urinary oxalate and citrate was satisfactory. Capillary electrophoresis is suited for routine examination of urinary oxalate and citrate with the advantage on simplicity and economy. The assay of plasma oxalate by this method was also acceptably sensitive, specific under a low temperature and an acidification.     

Formation of tamoxifen-DNA adducts via O-sulfonation, not O-acetylation, of alpha-hydroxytamoxifen in rat and human livers.

Tamoxifen (TAM) is used as the standard endocrine therapy for breast cancer patients and as a chemopreventive agent for women at high risk for this disease. Unfortunately, treatment of TAM increases the incidence of endometrial cancer; this may be due to the genotoxic damage induced by TAM metabolites. Formation of TAM-DNA adducts in rat liver correlates with the development of hepatocarcinoma. TAM-DNA adducts are proposed to be formed through O-sulfonation and/or O-acetylation of alpha-hydroxylated TAM and its metabolites. However, the role of O-sulfonation and O-acetylation in the formation of TAM-DNA adducts has not been extensively investigated. Rat or human hydroxysteroid sulfotransferases (HST), acetyltransferases, and liver cytosol were incubated with calf thymus DNA, alpha-OHTAM, and either 3'-phosphoadenosine 5'-phosphosulfate (PAPS) or acetyl coenzyme A (acetyl-CoA) as a cofactor and analyzed for TAM-DNA adduct formation, using 32P postlableling/polyacrylamide gel electrophoresis analysis. TAM-DNA adduct was formed when PAPS, not acetyl-CoA, was used. No TAM-DNA adducts were produced using human N-acetyltransferase I and II. HST antibody inhibited approximately 90% of TAM-DNA adduct formation generated by the cytosol or HST, suggesting that HST is primarily involved in the formation of TAM-DNA adducts. The formation of TAM-DNA adducts with rat liver cytosol and HST was much higher than that of human liver cytosol and HST. Our results indicate that TAM-DNA adducts are formed via O-sulfonation, not O-acetylation, of alpha-hydroxylated TAM and its metabolites.