Possible light-induced superconductivity in K3C60 at high temperature.

The non-equilibrium control of emergent phenomena in solids is an important research frontier, encompassing effects such as the optical enhancement of superconductivity. Nonlinear excitation of certain phonons in bilayer copper oxides was recently shown to induce superconducting-like optical properties at temperatures far greater than the superconducting transition temperature, Tc (refs 4-6). This effect was accompanied by the disruption of competing charge-density-wave correlations, which explained some but not all of the experimental results. Here we report a similar phenomenon in a very different compound, K3C60. By exciting metallic K3C60 with mid-infrared optical pulses, we induce a large increase in carrier mobility, accompanied by the opening of a gap in the optical conductivity. These same signatures are observed at equilibrium when cooling metallic K3C60 below Tc (20 kelvin). Although optical techniques alone cannot unequivocally identify non-equilibrium high-temperature superconductivity, we propose this as a possible explanation of our results.

Pressure tuning of light-induced superconductivity in K3C60.

Optical excitation at terahertz frequencies has emerged as an effective means to dynamically manipulate complex materials. In the molecular solid K3C60, short mid-infrared pulses transform the high-temperature metal into a non-equilibrium state with the optical properties of a superconductor. Here we tune this effect with hydrostatic pressure and find that the superconducting-like features gradually disappear at around 0.3 GPa. Reduction with pressure underscores the similarity with the equilibrium superconducting phase of K3C60, in which a larger electronic bandwidth induced by pressure is also detrimental for pairing. Crucially, our observation excludes alternative interpretations based on a high-mobility metallic phase. The pressure dependence also suggests that transient, incipient superconductivity occurs far above the 150 K hypothesised previously, and rather extends all the way to room temperature.

A modified rosette inhibition test in renal allotransplantation.

The rosette inhibition test, with a modification of the technique which enables highly accurate marking of T lymphocytes, has been employed in the followup of 55 renal transplant patients. The minimal inhibitory concentration of antilymphocyte globulin (that is, that concentration of antilymphocyte globulin causing 25% inhibition of rosette formation) was higher than 1:16,000 in 63 (97%) of 65 separate determinations made during acute rejection episodes, and lower than 1:16,000 in 377 (92%) of 410 determinations after which no clinical evidence of rejection developed. The results presented in this paper indicate that this modified test is a useful tool either to predict the occurrence of or to confirm the diagnosis of rejection.

Kelfiprim versus co-trimoxazole in recurrent and persistent urinary tract infections: multicenter double-blind trial.

Kelfiprim (KP) is a new bactericidal agent containing trimethoprim (T) and sulfametopyrazine (S), a long-acting sulfonamide (ratio 5:4). The posology is one capsule (T 250 mg + S 200 mg) daily, after a loading dose of two capsules on the first day. To evaluate the clinical value of Kelfiprim (KP) vs co-trimoxazole (CO) in urinary tract infection (UTI) a controlled multicenter double-blind trial (MDBT) was carried out in 76 patients suffering from persistent and recurrent UTIs. About 90 per cent response rate (sterile urine at the end of treatment) was obtained for KP and about 85 per cent for CO in recurrent UTI. In persistent UTI the rate of recovery was 66.8 per cent and 53 per cent for KP and CO, respectively. Safety of treatments was excellent in 97 per cent of patients treated with Kelfiprim and 87 per cent treated with co-trimoxazole. Two patients, one in each group, were dropped from the study because of adverse reactions.

Technical and economic strategies of maintenance dialysis in the UK and Nordic Countries.

The technical and economic strategies of maintenance dialysis in the UK and Nordic Countries are described. In particular the concept of 'Therapy Cost', or therapy pricing, as it is also known, in the UK and the concept of 'Patient Flow', which basically plots the flow of patients through the dialysis process, in the Nordic Region are discussed.

CAPD and systemic diseases.

A review is presented on the use of continuous ambulatory peritoneal dialysis (CAPD) in some systemic diseases with renal involvement to the stage of terminal renal failure: progressive systemic sclerosis, systemic lupus erythematosus, paraproteinemias and systemic amyloidosis. CAPD provides a suitable means of treatment of end-stage renal failure complicating systemic diseases both in terms of control of uremia and quality of life, being the treatment of choice in selected patients.

Hemodialysis without anticoagulants: efficiency and hemostatic aspects.

In 29 patients with high risk of bleeding, 111 hemodialyses have been performed without heparin (WHD) or other anticoagulants. The same patients were switched to low dose heparin dialysis (LDHD) as soon as the bleeding risk had ceased. The dialyzer had to be changed in 11 and the drip chamber in 20 WHDs because of partial clotting. This phenomenon did not occur during LDHD. The comparative efficiencies of the two techniques were evaluated by measuring the urea and creatinine clearances of the dialyzers. No significant difference between LDHD and WHD clearances was observed. In 7 of 29 patients, hemostasis variables were studied before, during and after both modes of treatment. Fibrinogen, platelet count, antithrombin III and prothrombin time did not differ with the different dialysis procedures. During dialysis, platelet factor 4 (PF4) levels were significantly higher than baseline values (P less than 0.01), with no difference between WHD and LDHD. Plasma fibrinopeptide A (FPA) levels remained normal during LDHD, but significantly increased during WHD (P less than 0.001). Our data indicate that WHD is feasible, with a low risk of extravascular coagulation. The bleeding risk is not increased during or after dialysis, and the danger of intravascular coagulation is low as confirmed by the isolated elevation of FPA plasma levels, unaccompanied by changes in other variables.

In vitro study of the flush effect in two reusable continuous ambulatory peritoneal dialysis (CAPD) disconnect systems.

Previously published in vitro results, confirmed by clinical studies, indicate that the use of a flush significantly reduces peritonitis in single-use and reusable continuous ambulatory peritoneal dialysis (CAPD) systems. Since reusable systems may use the flush plus inline disinfectant between exchanges, the question remains as to whether or not the flush could be used alone in all disconnect systems. Using an in vitro model, we evaluated the flush in two reusable disconnect systems that use both flush and disinfectant in vivo. In a series of twenty sets per organism per incubation (0 h and 10 h), Y sets were inoculated in the lumen with three pure cultures (10(3) CFU range). Ability of flush without disinfectant to clear sets of contamination was analyzed by collecting multiple samples at each step of the procedure, enriching with tryptone broth and verifying bacterial growth. When contaminated sets were not incubated, flush efficacy of the systems was consistent with previous data showing 100% removal of Staphylococcus epidermidis, but only partial elimination of Staphylococcus aureus and Pseudomonas aeruginosa. After incubation, simulating reusable systems, the flush was able to eliminate S. epidermidis less than 50% of the time. There was no significant difference in results between the two systems tested. Reusable systems allow more contact time between bacteria and plastic resulting in reduced flush efficacy suggesting that, for safest conditions, they should be used with inline disinfectants.

Intraperitoneal administration of phosphatidylcholine improves ultrafiltration in continuous ambulatory peritoneal dialysis patients.

Reports in the literature have linked a low phosphatidylcholine content in continuous ambulatory peritoneal dialysis (CAPD) effluent to ultrafiltration loss. Clinical evidence suggests that adding phosphatidylcholine to the dialysis solution enhances ultrafiltration. A clinical study has been designed to clarify the effect of phosphatidylcholine on ultrafiltration in CAPD patients with normal ultrafiltration. A weekly measurement of the peritoneal equilibration test was conducted per patient in the hospital. A comparison between the control dialysis solution (three-week period) and the phosphatidylcholine premixed solution (three-week period) was performed on a total of 12 patients. This study shows that a phosphatidylcholine premixed dialysis solution significantly enhances ultrafiltration. Since ultrafiltration per osmotic driving force (mL/g glucose) is enhanced, the patient's glucose load per day is reduced to achieve equal ultrafiltration. In the presence of phosphatidylcholine, peritoneal permeability remained unchanged, as indicated by membrane transport characteristics. No side effects were observed.

Short-term effects of low-calcium dialysis solutions on calcium mass transfer, ionized calcium, and parathyroid hormone in CAPD patients.

Patients on CAPD using calcium carbonate (CaCO3) as phosphate binder might benefit from low-calcium (Ca) concentration dialysis solutions; however, no data are available for the effects of this regimen on Ca metabolism. We studied 10 patients on stable CAPD regimens with standard dialysis solutions (Ca 7 mg/dL) who were taking CaCO3 to control hyperphosphatemia (mean daily doses 4.5 +/- 2.4 g). Hypercalcemic episodes had been recorded in 6 patients. Standard dialysis solutions were replaced with solutions containing 5 mg/dL of Ca. Calcium and phosphate peritoneal mass transfer (MT), serum concentrations of total Ca, ionized Ca (Ca++), phosphate, intact PTH, and mid-molecular PTH, were evaluated before and 48 hours after change of dialysate. The switch to low-Ca solutions was accompanied by significant changes in calcium mass transfer (Ca MT) (+9.84 +/- 48.22 versus -96.74 +/- 48.32 mg/day, p less than .001). Ca MT was significantly (p less than .05) correlated with the serum/dialysate Ca gradient. There was no difference in phosphate MT. Serum Ca++ significantly (p less than .05) decreased from 5.20 +/- 0.32 to 4.88 +/- 0.36 mg/dL, and intact PTH significantly increased (81.5 +/- 139 versus 112.4 +/- 168 pg/mL, p less than .05). It is concluded that dialysis solutions with Ca 5 mg/dL result in a negative peritoneal Ca MT and can be useful to prevent and treat hypercalcemia in CAPD patients taking CaCO3 as phosphate binder. A careful monitoring of ionized calcium, PTH, and phosphate is suggested when an extensive and long-term use of this solution is considered.

Continuous ambulatory peritoneal dialysis (CAPD) of children with amino acid solutions: technical and metabolic aspects.

The changes in plasma and dialysate amino acids (AA) in 7 continuous ambulatory peritoneal dialysis (CAPD) children after dialysis with a 1% AA solution were compared with a glucose-containing solution. During the AA-exchange, the plasma levels of individual AA reached their peaks after 1 h, with their percentage increments significantly correlated (p less than 0.001) with the ratio of the amount of AA in the bag to the basal plasma concentration. The plasma concentration of methionine, valine, phenylalanine, and isoleucine remained higher than the basal value at 4 h. The amount of AA absorbed was 66% after 1 h, and 86% after 4 h and 6 h, corresponding to 2574 +/- 253 mumol/kg body wt. During glucose-dialysis (1.36%), levels of histidine, methionine, valine, phenylalanine, and isoleucine were significantly decreased in plasma after 1 h, and stayed low throughout the dialysis period. The loss of AA with the peritoneal effluent was 116 +/- 69 mumol/kg/body wt. From this study, it seems that using an AA dialysis solution, with 1 exchange per day, might limit the daily glucose load and compensate for AA losses by supplying an extra amount of AA and by reducing the loss of other AA not contained in dialysis solutions. The AA pattern in plasma following AA-dialysis resembles that observed after a protein meal, with no signs of persistently high, nonphysiological levels.

A multicenter, selection-adjusted comparison of patient and technique survivals on CAPD and hemodialysis.

Four hundred and eighty CAPD and 373 HD patients started regular dialysis treatment between 1981 and 1987 in 6 dialysis centers. The CAPD patients were 6 years older, on average, than the HD patients and had more complicating conditions (43.3% with 3 or more coexisting risk factors versus 28.9% with coexisting complications). The 7-year patient survival rate was not significantly different. Cox's proportional hazards regression showed that age, cardiovascular disease, cerebrovascular disease, peripheral vascular disease, diabetes, malignancy and multisystem disease had significant adverse effects on patient survival. After correcting for the influence of these factors, no significant differences in patient survival were seen. However, after 53.5 years of age, the increase in the risk of death was significantly higher in HD than in CAPD patients. Technique survival was significantly different in the 6 centers and was better for HD than for CAPD. There was no statistically significant difference between CAPD and HD technique survival when peritonitis was eliminated as a cause of failure. Based on this 7 year analysis, CAPD would appear to be an excellent alternative to HD.

Peritoneal dialysis solution calcium concentration regulates peritoneal fibroblast proliferation in CAPD.

Peritoneal fibrosis remains one of the major causes of dropout in continuous ambulatory peritoneal dialysis (CAPD), by reducing ultrafiltration capacity. Since studies in vitro have shown that cytoplasmic Ca2+ regulates the proliferation of most cell lines and the release of cytokines from immune cells, eight uremics and four controls at the start of CAPD were evaluated for the in vitro effects of different peritoneal dialysis solution (PDS) Ca2+ concentrations (1, 1.25, 1.75, and 2 mmol/L) on: 1) peritoneal fibroblast (PF) proliferation; 2) peritoneal macrophage (PM) and peritoneal lymphocyte (PL) release of interleukin-1 (IL-1) and interferon-gamma (IFN-gamma)--cytokines that are known to induce PF proliferation; and 3) cytoplasmic Ca2+ concentrations in PF, PM, and PL. Results showed that in both the uremics and controls, increasing the dose of Ca2+ in the medium induced a dose-dependent rise in PF proliferation, and in the release of IL-1 and IFN-gamma from PM and PL. Meanwhile, the cytoplasmic Ca2+ concentration of PF, PM, and PL also increased. With a PDS containing 1 mmol/L of Ca2+ in the uremics, these parameters were below normal; they exceeded the norm with a Ca2+ concentration of 1.75 and 2 mmol/L, and were normal with a Ca2+ concentration of 1.25 mmol/L. These data suggest that in CAPD patients, the use of a low Ca2+ PDS (1 and 1.25 mmol/L) may be useful in reducing the proliferation of PF and the production of IL-1 and IFN-gamma from PM and PL, thereby preventing peritoneal sclerosis.

Branched chain and aromatic free amino acids in plasma and skeletal muscle of uremic patients undergoing hemodialysis and CAPD.

Plasma and skeletal muscle free amino acids were measured in patients submitted to Hemodialysis (HD) or Continuous Ambulatory Peritoneal Dialysis (CAPD) in order to evaluate the effects of these different dialysis modalities on amino acid pools; the data were compared with those obtained in control subjects and in patients with advanced Chronic Renal Failure (CRF) not submitted to Regular Dialysis Treatment (RDT). Our findings show low intracellular concentrations of VAL, total Branched Chain Amino Acid (BCAA) and TYR in uremic patients treated with CAPD but not in those undergoing HD. The observed differences in muscle amino acid pattern could be well explained by a changed amino acid metabolism regulation in CAPD, possibly related to the sustained hyperinsulinism and to an increased rate of hepatic protein synthesis.

Bone marrow erythroid precursor Ca++ regulates the response to human recombinant erythropoietin (rHuEPO) in hemodialysis patients.

The modulation of erythropoiesis by erythropoietin is conditioned by the concentration of Ca++ in the cytoplasm of the bone marrow erythroid precursors. We evaluated in vitro erythroid colony development from bone marrow erythroid precursors incubated with increasing concentrations of Ca++ or Ca++ plus 1,25 (OH)2 D3, and bone marrow erythroid precursor cytoplasmic Ca++ concentrations in 10 anemic hemodialysis (HD) patients before and during rHuEPO therapy. Results showed that: a) in vitro: in uremics patients before rHuEPO therapy, bone marrow erythroid precursor cytoplasmic Ca++ was lower than in normal subjects; the addition of Ca++ to the bone marrow erythroid precursors induced a dose-dependent Ca++ and erythroid colony development increase; 1,25 (OH)2 D3 potentiated this effect; b) in vivo: rHuEPO normalized bone marrow erythroid precursor Ca++ and erythroid colony development. An inverse correlation was seen between bone marrow erythroid colony development, precursor CA++ before therapy, the in vitro erythroid and the rHuEPO dose needed in vivo to normalize hematological parameters. These data emphasize the role of Ca++ in erythropoiesis and may aid understanding of the mode of action of rHuEPO in HD.

A new catheter to prevent exit-site infection in peritoneal dialysis.

In order to prevent exit-site infection, we studied a new Tenckhoff-derived catheter, named the "Malpighi catheter," capable of avoiding sinus tract formation. The outer cuff of this new device is 3.5 cm long and is deliberately positioned half-extruded; in fact, half of the cuff remains outside the skin exit-site. The implantation technique is identical to that of the standard two-cuff Tenckhoff catheter. We implanted eight Malpighi catheters in 5 CAPD and 3 IPD patients. The observation period was 146 patient-months (range 14-23, M +/- SD 18.2 +/- 3.3). We observed excellent adhesion between the outer cuff and surrounding tissue. Actually, by pulling the catheter the skin around the half-extruded cuff becomes cone-shaped, with the cone's apex tightly stuck to cuff and the sinus tract disappearing completely. Only one case of exit-site infection by Staphylococcus aureus and two cases of ulcer of the skin beneath the external part of the half-extruded cuff were observed. These complications were resolved completely. No catheter needed to be removed and there were no leakages. The histological study of the cuff showed a good infiltration of the dacron cuff by fibrous tissue. On the grounds of our preliminary experience, we believe that the absence of the sinus tract, the formation of an efficient mechanical and bacterial barrier and the reduction of exit-site infection incidence are all factors that encourage further research.

Peritoneal dialysis fluid (PDF) C++ and 1,25(OH)2D3 modulate peritoneal macrophage (PM0) antimicrobial activity in CAPD patients.

Our previous in vitro studies have shown that Ca++ and 1,25(OH)2D3 modulate peritoneal macrophage (PMO) antimicrobial activity in CAPD patients. We thus evaluated in vivo in 24 CAPD patients (12 who had never had peritonitis and 12 with an overall peritonitis incidence of more than one episode per 8 patient/month), the effects of different peritoneal dialysis fluid (PDF) Ca++ concentrations (1.25, 1.75 and 2.25 mmol/L) on PMO: 1. cytoplasmic Ca++ concentration; 2. superoxide generation; 3. Leukotriene B4 (LTB4) release; 4. bacterial killing for staphylococcus epidermidis. The same parameters were also evaluated after adding 1,25(OH)2D3 (0.25 microgram/L) to the PDF. Results showed a direct correlation between the PDF Ca++ concentration and PMO Ca++ levels, superoxide and LTB4 generation, and bacterial killing, such that with 2.25 mmol/L of Ca++ these values were significantly higher than those seen with 1.75 mmol/L. The addition of 1,25(OH)2D3 potentiated the Ca++ - induced effects. On the contrary, with PDF Ca++ levels of 1.25 mmol/L, an inhibition of the aforementioned parameters was seen. However, this effect was reversed by the addition of 1,25(OH)2D3. These in vivo results confirm the importance of Ca++ and 1,25(OH)2D3 in PMO antibacterial functions in CAPD patients and may be useful in the prophylaxis and therapy of peritonitis.

Ca++ and 1,25(OH)2D3 enhance peritoneal macrophage (PMPhi) antimicrobial functions in CAPD.

Ca++ has been proposed as an intracellular second messenger for the activation of immune cells. An immune regulatory role for 1,25(OH)2D3 has also been suggested. We therefore evaluated the role of Ca++ and 1,25(OH)2D3 in the depressed antibacterial functions of 8 CAPD patients with relapsing bacterial peritonitis by evaluating in vitro the effects of escalating concentrations of 1,25(OH)2D3 and/or Ca++ on: 1. peritoneal macrophage (PMO) cytoplasmic Ca++; 2. PMO superoxide generation; 3. PMO leukotriene B4 release, 4. PMO bacterial killing. Results showed a dose-dependent increase in all parameters for Ca++ concentrations from 500 to 3,000 microM while with both a CA(++)-free medium and with Ca++ concentrations of 5,000 microM of medium all the aforementioned functions were abrogated. Addition of low doses of 1,25(OH)2D3 strongly potentiated the stimulatory effect of Ca++ on cell functions, while high doses were inhibitory. These in vitro data underline the importance of Ca++ and 1,25(OH)2D3 in PMO antibacterial functions in CAPD patients, and may be useful in the prophylaxis and therapy of peritonitis.

Effects of Ca++ and 1,25(OH)2D3 on peritoneal immune-cell cytokine release and fibroblast proliferation in CAPD patients.

We have demonstrated the role in some CAPD patients with ultrafiltration (UF) loss of an increased peritoneal lymphocyte (PLy) and macrophage (PMO) Ca++ concentration in the release of large amounts of gamma-Interferon (gamma-IFN) and Interleukin-1 (IL-1), which stimulate peritoneal fibroblast proliferation. We have also shown in vitro and in vivo that the calcium channel blocker verapamil (VPM) is able to normalize the previously high Ca++ PLy and PMO concentration and cytokine release, to decrease fibroblast proliferation, and to increase UF in only 60% of the CAPD patients with UF loss due to a cytokine-mediated hyperproliferation of peritoneal fibroblasts, while in the remaining 40% there is little improvement in UF (VPM responders and low-responders, respectively). To evaluate which mechanisms in addition to passive Ca++ influx can play a role in the Ca(++)-dependent activation of peritoneal immune-cells, we evaluated in 6 CAPD VPM low-responder patients the effects of in vitro of different doses of Ca++ and 1,25(OH)2D3 on: 1) PLy and PMO cytoplasmic Ca++ levels in the PLy and PMO cytoplasm; 2) gamma-IFN and IL-1 release by PLy and PMO; 3) peritoneal fibroblast proliferation. Results showed a direct correlation between Ca++ levels in the medium and the PLy and PMO Ca++ concentrations, IL-1 and gamma-IFN release, and peritoneal fibroblast proliferation. These effects were enhanced by the addition of low doses of 1,25(OH)2D3 to the medium, while both high 1,25(OH)2D3 doses and verapamil abrogated the Ca+(+)-induced PLy and PMO activation. These results underline the importance of both Ca++ and 1,25(OH)2D3 in peritoneal immune-cell activation and peritoneal fibroblast proliferation, and may offer a new prophylactic approach for preventing UF loss in CAPD.

Effect of monophosphoryl lipid A (MPLA) on peritoneal leukocyte function.

We analyzed the in vitro effects of monophosphoryl lipid A (MPLA), a nontoxic bacterial endotoxin-derived immunomodulant, on the depressed immune functions of peritoneal lymphocytes (PLy) and macrophages (PMO) of 6 CAPD patients with relapsing bacterial peritonitis. MPLA was also tested for its capacity to stimulate the peritoneal fibroblast proliferation as determined by 3H-thymidine incorporation. In vitro incubation of PLy and PMO with escalating doses of MPLA up to 5 micrograms/ml, resulted in a dose-dependent enhancement of Gamma-Interferon (Gamma-IFN) and Interleukin-2 (IL-2) production by PLy, and Interleukin-1 (IL-1) by PMO. There was also an increase in PMO bacterial killing and membrane Fc receptor number, while no change in peritoneal fibroblast proliferation was seen with any of the MPLA concentrations tested. These results suggest that the peritoneal leukocyte abnormalities observed in some high peritonitis rate CAPD patients may be reversed, to some degree, by MPLA, without directly inducing a potentially deleterious peritoneal fibrosis.