Sodium ramping in hemodialysis: a study of beneficial and adverse effects

Sodium ramping has been introduced as a technique to decrease side effects occurring during hemodialysis. We studied sodium ramping in 414 dialysis sessions in 23 patients by randomizing 2-week blocks of dialysis to either steady dialysate sodium of 140 mEq/L, linear sodium ramping during dialysis from 155 mEq/L to 140 mEq/ L, or stepwise ramping (sodium of 155 mEq/L for 3 hours and 140 mEq/L for 1 hour). We studied the number and severity of hypotensive and hypertensive episodes. A hypotensive episode was defined as an abrupt decline of systolic blood pressure of more than 50 mm Hg, a decrease in blood pressure accompanied by symptoms requiring intervention, or systolic blood pressure of less than 90 mm Hg even without symptoms. A hypertensive episode was defined as a sudden increase in systolic blood pressure of over 30 mm Hg. We also recorded other side effects (headache, cramps, nausea, vomiting, dizziness, thirst, fatigue, weight gain, and blood pressure) during, immediately after, and between dialysis sessions. There was no major difference between the two ramping protocols, but compared with standard dialysis, both decreased total number of side effects from 4.0 to 3.0 (P = 0.057); the number of hypotensive episodes decreased from 1.3 to 0.7 (P = 0.036). The lowest blood pressure was 114/66 mm Hg during control and 123/69 mm Hg during ramping (P < 0.0001). The frequency of cramps during dialysis decreased from 0.9 to 0.5 (P = 0.006). There was no difference in headache, nausea, or vomiting. The number of hypertensive episodes increased from 0.045 to 0.086 during ramping (P = 0.125). Of 23 patients, only five (22%) had a marked decrease in symptoms; two of the three most symptomatic patients showed no significant improvement. Between dialysis sessions, patients complained of more fatigue and thirst (P < 0.0001 and P = 0.0028, respectively), and interdialytic weight gain following ramping was 5.1% of body weight compared with 4.4% without ramping (P < 0.0001). Blood pressure also increased following ramping, from 143/79 mm Hg to 152/81 mm Hg (P = 0.001). Ramping can decrease the overall number of side effects, but increases interdialytic symptoms, weight gain, and hypertension. In most instances, it simply changes the time the side effects occur. Only 22% of patients have significant benefit. These patients can be identified only through trial and error, as no model of these patients can be created.     

Primary chemotherapy for stage 2 testis cancer

To evaluate the efficacy and toxicity of primary chemotherapy in patients with stage 2 (retroperitoneal lymph node metastases) testis cancer, 20 consecutive patients referred to Groote Schuur Hospital between September 1992 and March 1994 were reviewed. There were 10 patients with non-bulky non-seminomatous germ cell tumour (NSGCT), 5 with bulky NSGCT and 5 with bulky seminoma. The treatment regimen consisted initially of 4 cycles of cisplatin, etoposide and bleomycin. Patients with NSGCT and a residual mass after chemotherapy subsequently underwent retroperitoneal lymph node dissection (RPLND) and those with seminoma underwent a low dose of irradiation to the mass. In 7 (70%) of the 10 patients with non-bulky NSGCT, there was a complete response to chemotherapy and 3 patients underwent limited RPLND. One patient relapsed at follow-up but remains clear of disease after salvage therapy. The survival rate is 100% at a median follow-up of 60 months (range 12-143 months). In 5 patients with bulky NSGCT there was no complete response to chemotherapy. Three have undergone limited RPLND. The survival rate is 52% at a median follow-up of 130 months (range 108-152 months). In 5 patients with bulky seminomas, the survival rate is 100% at a median follow-up of 55 months (range 29-92 months). Toxicity has been modest except for 1 patient who died postoperatively in the early part of the study. Four patients have fathered children after treatment. We conclude that primary chemotherapy is the treatment of choice for patients with stage 2 testis cancer.     

Inhibition of in vivo tumorigenicity and invasiveness of a human glioblastoma cell line transfected with antisense uPAR vectors

Our previous studies showed that glioblastomas express increased urokinase-type plasminogen activator receptors (uPARs) in comparison to low-grade gliomas (Yamamoto et al., Cancer Res., 54, 5016-5020, 1994). To explore whether downregulation of uPAR inhibits tumor formation and invasiveness, a human glioblastoma cell line was transfected with a cDNA construct corresponding to 300 bp of the human uPAR's 5' end in an antisense orientation, resulting in a reduced number of uPA receptors. Co-culture studies with tumor spheroids and fetal rat brain aggregates showed that antisense SNB19-AS1 cells expressing reduced uPAR failed to invade fetal rat brain aggregates. Intracerebral injection of SNB19-AS1 stable transfectants failed to form tumors and were negative for uPAR expression in nude mice. Thus uPAR appears in this model to be essential for tumorigenicity and invasion of glioblastomas in vivo.     

Improved supercontinuum generation through UV processing of highly nonlinear fibers

We demonstrate that UV exposure of highly nonlinear, germano-silicate fibers can significantly broaden the infrared supercontinuum generated by femtosecond pulses in these fibers. Both simulations and measurements of the fiber chromatic dispersion show that UV-induced refractive index changes increase the waveguide dispersion by up to 5 ps/(nm-km) at 1570 nm and shift the dispersion zero by over 100 nm. We examine fibers with a range of UV exposure levels and show that the short wavelength edge of the supercontinuum can be continuously changed by more than 100 nm. We also show that the long wavelength edge is extended beyond that of the unexposed fiber. The resulting continuum spans from 0.85 to 2.6 /spl mu/m. Cutback measurements show that the supercontinuum in the exposed fiber is generated in as little as 1 cm of fiber. A nonlinear Schro/spl uml/dinger equation (NLSE) model of the supercontinuum generation in the nonlinear fiber shows that the short wavelength behavior of the continuum is primarily controlled by changes in the fiber dispersion caused by the UV-induced change in refractive index of the fiber core.     

Universal prediction

This paper consists of an overview on universal prediction from an information-theoretic perspective. Special attention is given to the notion of probability assignment under the self-information loss function, which is directly related to the theory of universal data compression. Both the probabilistic setting and the deterministic setting of the universal prediction problem are described with emphasis on the analogy and the differences between results in the two settings     

Differences in weight gain in relation to race, gender, age and education in young adults: the CARDIA Study. Coronary Artery Risk Development in Young Adults

Copper/zinc (Cu/ZnSOD) and manganese (MnSOD) superoxide dismutases which catalyze the dismutation of toxic superoxide anion, O(2-)-, to O2 and H2O2, play a major role in protecting cells from toxicity of oxidative stress. However, cells overexpressing either form of the enzyme show signs of toxicity, suggesting that too much SOD may be injurious to the cell. To elucidate the possible mechanism of this cytotoxicity, the effect of SOD on DNA and RNA strand scission was studied. High purity preparations of Cu/ZnSOD and MnSOD were tested in an in vitro assay in which DNA cleavage was measured by conversion of phage phi X174 supercoiled double-stranded DNA to open circular and linear forms. Both types of SOD were able to induce DNA strand scission generating single- and double-strand breaks in a process that required oxygen and the presence of fully active enzyme. The DNA strand scission could be prevented by specific anti-SOD antibodies added directly or used for immunodepletion of SOD. Requirement for oxygen and the effect of Fe(II) and Fe(III) ions suggest that cleavage of DNA may be in part mediated by hydroxyl radicals formed in Fenton-type reactions where enzyme-bound transition metals serve as a catalyst by first being reduced by superoxide and then oxidized by H2O2. Another mechanism was probably operative in this system, since in the presence of magnesium DNA cleavage by SOD was oxygen independent and not affected by sodium cyanide. It is postulated that SOD, by having a similar structure to the active center of zinc-containing nucleases, is capable of exhibiting non-specific nuclease activity causing hydrolysis of the phosphodiester bonds of DNA and RNA. Both types of SOD were shown to effectively cleave RNA. These findings may help explain the origin of pathology of certain hereditary diseases genetically linked to Cu/ZnSOD gene.     

Collision-induced signal enhancement: a method to increase product ion intensities in MS/MS and MSn experiments

Collision-induced signal enhancement (CISE), a new technique to enhance the MSn capabilities of the quadrupole ion trap, is demonstrated. CISE is based on the chemistry, i.e., the dissociation pathways, of the analyte examined. Polysaccharides up to hexamers are used to demonstrate the capabilities of CISE to enhance signal in two distinct functional modes. Mode 1 CISE is designed to enhance the signal of an ion desired for MSn analysis. Mode 2 CISE is designed to enhance structurally significant product ions in an MS/MS spectrum. Two different approaches can be utilized to effect the two functional modes of CISE. Both approaches use conventional resonant excitation techniques to effect dissociation, which is performed nonanalytically, i.e., without isolation of the ions to be dissociated. The two approaches are (1) single-frequency resonance excitation, and (2) broad-band wave form resonant excitation. Experimental results for Mode 1 CISE analysis demonstrate up to a 17.3-fold signal increase for the single-frequency approach and 5.3-fold using broad-band excitation. Mode 2 CISE analysis shows up to a 16.3-fold increase in signal strength with single-frequency excitation and 3.3-fold using broad-band excitation.     

Effects of cytosolic Ca2+ on the Ca2+ content of the sarcoplasmic reticulum in saponin-permeabilized rat ventricular trabeculae

After a brief presentation of the development of free walking interpreted as learning dynamical equilibrium, the problem of sensory integration in the process of walking development is discussed. A critical review of the role of vision in the development of posturo-locomotor task is presented, along with recent test results on the development of the vestibular system. A final section presents the development of head stabilization and coordination as a necessary means to assist sensory integration. It is suggested that if sensory information is necessary to enhance posturo-locomotor skills, a good mastery of walking is in turn necessary to increase the efficiency of sensory integration.