Muon-spin rotation measurements of an unusual vortex-glass phase in the layered superconductor Bi2.15Sr1.85CaCu2O8+δ.

Muon-spin rotation measurements, performed on the mixed state of the classic anisotropic superconductor Bi(2.15)Sr(1.85)CaCu(2)O(8+δ), obtain quantities directly related to two- and three-body correlations of vortices in space. A novel phase diagram emerges from such local probe measurements of the bulk, revealing an unusual glassy state at intermediate fields which appears to freeze continuously from the equilibrium vortex liquid but differs both from the lattice and the conventional high-field vortex glass state in its structure.

Varicella zoster infection in renal transplant recipients: prevalence, complications and outcome.

Varicella zoster virus (VZV) is an important pathogen after renal transplantation. In the present study, we examined the prevalence, clinical presentation and outcome of VZV infections in renal transplant recipients. Charts and medical records of adult renal allotransplant recipients were investigated to find patients with VZV infection. From December 1972 until July 2010, 1,139 patients received kidney allograft at our institution. VZV infection was diagnosed in 40 patients (3.51%). 28 patients (70%) had intensified immunosuppression prior to VZV infection occurrence. Median time of onset was 2.13 years after transplantation (range 9 days to 19.2 years). 35 patients developed VZV during the first post-transplant year (median 0.61 years). Four patients developed VZV infection more than 12 years after transplantation. 33 patients (82.5%) had dermatomal distribution, 5 (12.5%) disseminated herpes zoster (HZ), and 2 patients (5%) who were VZV IgG-negative before transplantation, developed chickenpox. Immunosuppression was reduced and patients received acyclovir. Cutaneous scarring was recorded in 7 cases (17.5%). Two patients developed post-herpetic neuralgia, which was accompanied by scarring and skin depigmentation in 1 of them. Five patients (12.5%) experienced relapse of HZ. Timely initiation of therapy may prevent development of complications and the visceral form of disease. Based on our experience with development of chickenpox, we suggest active immunization for all seronegative patients before organ transplantation.

Quantum critical behaviour in a high-T(c) superconductor.

Quantum criticality is associated with a system composed of a nearly infinite number of interacting quantum degrees of freedom at zero temperature, and it implies that the system looks on average the same regardless of the time- and length scale on which it is observed. Electrons on the atomic scale do not exhibit such symmetry, which can only be generated as a collective phenomenon through the interactions between a large number of electrons. In materials with strong electron correlations a quantum phase transition at zero temperature can occur, and a quantum critical state has been predicted, which manifests itself through universal power-law behaviours of the response functions. Candidates have been found both in heavy-fermion systems and in the high-transition temperature (high-T(c)) copper oxide superconductors, but the reality and the physical nature of such a phase transition are still debated. Here we report a universal behaviour that is characteristic of the quantum critical region. We demonstrate that the experimentally measured phase angle agrees precisely with the exponent of the optical conductivity. This points towards a quantum phase transition of an unconventional kind in the high-T(c) superconductors.

Bone density in renal transplant recipients and in patients with chronic kidney disease: a follow-up study in children and adolescents.

AIMS: Disturbances in mineral and bone metabolism are common in patients with chronic kidney disease. The purpose of this follow-up study was to compare the change of bone mineral density in patients with chronic kidney disease to those who have received the renal transplant. METHODS: The study included 47 children and adolescents: 16 with mild to moderate kidney disease, 14 on dialysis and 17 patients with renal transplant. At the baseline and follow-up visits, regular biochemistry, anthropometry and bone mineral density were measured. To minimize the effect of skeletal size, bone mineral apparent density (BMAD; g/cm3) was calculated. RESULTS: The mean height was below one standard deviation from reference values in patients on dialysis and in those with renal transplant. After correction for age, baseline and follow-up BMAD did not differ significantly between patients after transplantation and those with chronic kidney disease. The increase of BMAD between two measurements (mean period 16.0 +/- 4.4 months) was not significantly higher in patients with kidney transplant compared to those with chronic kidney disease. The significant predictors of BMAD were PTH in patients with chronic kidney disease and duration of steroid therapy in patients with renal transplant. CONCLUSIONS: The results showed that bone density in children and adolescents, even several years after kidney transplantation, did not significantly change over time comparing to patients with chronic kidney disease. Hyperparathyroidism and steroid therapy were the most important risk factors for the slow increase of bone density.

Outcome after renal transplantation in a "senior" program: the Croatian experience.

BACKGROUND: The Eurotransplant "senior" program allocates kidneys from elderly donors to patients >65 years old. It aims to increase the number of renal transplantations. Kidneys are allocated locally without human leukocyte antigen (HLA) matching to decrease the cold ischemia time. Croatia has introduced its own "senior" program based on HLA matching. We compared results with those from Eurotransplant. METHODS: We identified and prospectively followed all patients aged of >or=65 years who underwent a first renal transplantation. We recorded their HLA matching, cold ischemia time, renal function, surgical and medical complications, and duration of hospitalization. RESULTS: Through October 2007, 22 elderly patients received an allograft from donors who were >65 years old. There were 8 female and 14 male patients of mean age at transplantation of 67.4 years. Mean donor age was 66 years. The number of HLA mismatches ranged from 1 to 5, and cold ischemia time from 7 to 15 hours. One-year patient survival was 95.4%, and graft survival was 81.8%. Delayed graft function, defined as the need for dialysis for >7 days after transplantation, occurred in 63.6% of patients. Older recipients required prolonged hospitalization after transplantation (45 days; range, 16-131). Frequent posttransplant complications included posttransplant diabetes mellitus in 1 patient, delayed wound healing in 5 patients, and lymphocoel in 2 patients. Maligancies occurred in 3 patients, neoplasm of the native kidney, posttransplant lymphoproliferative disease, and skin cancer. One patient experienced acute rejection that was successfully treated with steroids. Seventeen patients experienced 20 viral infections. There was only 1 serious infection (pulmonary tuberculosis). The major problems were cardiovascular complications which occurred in 40.9% of patients.

Octogenarians on hemodialysis: a prospective study.

Octogenarians represent the fastest growing group of patients on hemodialysis. These patients were previously treated with conservative measures, while they were believed to have too poor prognosis on renal replacement therapy. We investigated clinical characteristics and outcome of patients prospectively after at least 2 years of follow-up. Six male and six female patients who were older than 80 years at the start of hemodialysis were followed up. Their clinical characteristics, comorbidities, etiology of renal disease, nutritional status, complications, vascular access, hospitalizations, compliance and outcome were recorded. The primary renal disease was unknown in 42.8% of patients. All patients had one or more comorbid conditions. Dialysis was initiated in an emergency situation in 64.3%. Vascular access was long-term hemodialysis catheter in 71.4%. Only 14.2% of them received erythropoietin. There were no major bleedings with reduced doses of heparin. The most common complications were catheter-related ones (infections, ruptures). All patients together required seven hospitalizations per year (0.58 per patient). The octogenarians tended to be underdialyzed with the mean adequacy of dialysis (Kt/V) 0.92. The 1-year survival was 71.4%, and 2-year survival was 50%, i.e., they had good survival on hemodialysis. Most of them died from causes that were not related to the uremia. Their treatment requires a careful planning of renal service expansion while more octogenarians who need renal replacement treatment may be expected.

Renal transplantation in patients with Balkan endemic nephropathy.

BACKGROUND: Balkan endemic nephropathy (BEN) is a chronic tubulointerstitial disease prevalent in Croatia, Romania, Bulgaria, Bosnia and Herzegovina, and Serbia. In addition to renal disease, an increased incidence of upper urothelial carcinomas (UUCs) has been observed in the foci of BEN. Carcinoma may occur alone or in combination with BEN. Immunosuppression is associated with an increased risk for development of different malignancies. There are no data in the literature about the outcome of patients with BEN after transplantation. METHODS: We performed a retrospective evaluation of the database and review of the charts and pathology reports of 601 renal transplant recipients treated at our institution. RESULTS: From January 1995 to December 2004, kidney transplantations were performed in nine patients with BEN. One-year graft survival was 100%. A man, who was transplanted in 1997 died 2 years after transplantation with a functioning graft due to disseminated cancer from the pelvis of his own kidney. A female patient developed UCC 2 years after transplantation. They were both treated with a bolus of methylprednisolone before transplantation, because of four HLA-mismatches. A male patient developed UCC in the native and transplanted kidneys. He underwent a native nephroureterectomy with partial nephroureterectomy of transplanted kidney. His graft function was preserved with decreased immunosuppression. Three years later a urinary bladder carcinoma was discovered on a regularly performed multislice computed tomography. One patient developed a skin malignancy. Other patients have had uneventful posttransplantation courses with excellent graft function. Thus, 33.3% of patients with BEN developed UUC, compared with a 0.67% prevalence of urinary tract tumors among transplanted patients with other causes of end-stage renal disease. CONCLUSION: Patients with BEN are at increased risk for the development of UCC after transplantation. Regular screening for early detection of malignancy is mandatory. Longer follow-up and results from other transplant centers are needed to further investigate the relationship between BEN and UCC after renal transplantation.

Does mycophenolate mofetil increase the incidence of cytomegalovirus disease compared with azathioprine after cadaveric kidney transplantation?

Although most of the published papers had not found increase in the incidence of CMV disease in kidney transplant recipients treated with mycophenolate mofetil (MMF), we had feeling from everyday practice that after its introduction number of patients with CMV disease has increased. To test this hypothesis, we performed retrospective analysis of our database, comparing the incidence of CMV disease in patients treated with azathioprine (AZA) and patients treated with MMF. CMV disease was defined as CMV antigenemia (positive CMV pp65 determined by ELISA test) plus any of the following: decrease leucocytes or platelets, increased transaminases, increase in serum creatinine. The azathioprine treated group (AZA group) included 280 patients (132 female) treated for 17,672 months with AZA + Cyclosporine A (CyA) + steroid, or AZA + steroid, while the MMF group included 219 patients (112 female) treated for 5079 months with MMF + CyA + steroid, or MMF + steroid. There was no difference in acute rejection episodes between the AZA and the MMF group. The AZA group had 51 CMV disease episodes (1 episode per 346.5 treatment months), and the MMF group experienced 43 episodes (1 per 118.1 months) (P < .01). Mean onset of CMV disease was 32.65 +/- 47.69 (SD) months after transplantation in the AZA group, and 3.72 +/- 4.43 in the MMF group. There was no difference between two treatment groups regarding the donor-recipient CMV status mismatch. Despite having the increased incidence of CMV disease, MMF group had less severe disease compared to AZA group with decrease in leukocyte count in 11.6% vs 15.7% of episodes, decrease in platelet count in 20.9% vs 21.6%, elevation of transaminases in 18.6% vs 29.4% respectively, and finally increase in serum creatinine greater than 20% in 51.2% in MMF vs 74.5% in AZA group. Five patients from the AZA group experienced CMV pneumonitis with the mortality rate of 80%. Only one patient from the MMF group had CMV pneumonitis, and he survived. According to our results, patients treated with MMF have increased risk for development of CMV disease. However, the disease course is less severe, and less frequently accompanied with deterioration of renal function in comparison to the AZA group.

Pulmonary sarcomatoid carcinoma in a renal transplant recipient.

Sarcomatoid carcinomas (SC) are rare malignancies with concomitant occurrence of both carcinomatous and sarcomatous components. Although it may occur throughout the body, lungs are only very rarely involved. We present the first documented case of pulmonary SC (PSC) in a renal transplant recipient, and discuss clinical presentation, diagnostic procedures, treatment, and outcome.

The role of arterial hypertension in progression of renal failure.

The effect of arterial hypertension on the progression of chronic renal failure (CRF) was evaluated in 108 patients who eventually required dialysis in the 8 year period of the study. Patients' average serum creatinine (SCr) concentration at first examination was 239.7 +/- 45.3 mumol/liter and at the start of dialysis was 1,661.0 +/- 181.9 mumol/liter. The mean duration of pre-dialysis follow-up was 53.7 +/- 15.7 months. The mean monthly increase in SCr was 18.8 +/- 13.4 and 2.1 +/- 1.4 mumol/liter/month in hypertensive and normotensive CRF patients, respectively (P < 0.001). The CRF patients with a diastolic blood pressure (BP) < 89 mm Hg had a significantly (P < 0.05) slower rate of decline in renal function than the patients with a diastolic BP > or = 90 mm Hg. There was a significant relationship between a mean diastolic BP > or = 90 mm Hg and the rate of monthly increase in SCr (r = 0.81, P < 0.001). These data indicate that control of diastolic BP in CRF patients is a potentially effective way to slow the rate of decline in renal function.

Serum gastrin concentration in chronic renal failure.

On the basis of the existing experimental and clinical studies about the factors affecting the appearance of hypergastrinemia in renal failure, it can be concluded that the kidney plays an important, but not the only, role in the degradation of endogenous gastrin in humans. In this process the key role is played by the blood flow through the kidney, the preservation of the peritubular capillary system, and the functional kidney mass. Glomerular filtration has no particular importance in the extraction of gastrin from the circulation, while through the urine only a small amount of gastrin is excreted. In the decomposition of a part or at least some molecular gastrin forms, an important role is played by the capillary systems of extra-renal tissue. One further conclusion is that hypergastrinemia in patients with renal failure is the result of the combined effects of the reduced catabolism of gastrin in the kidney and its increased synthesis which is for the most part connected with hypochlohydria and secondary hyperparathyroidism. In patients with renal failure there exists the inhibition of the gastrin acid secretion which is the cause of the weakening of the mechanism of the feedback connection between HCl and gastrin, while because of a permanent stimulation of G-cells, the hyperplasia of these cells develops, as well as the increased secretory activity, and hypergastrinemia. Parietal cells become less sensitive to a permanently increased serum gastrin concentration but still capable of reacting to the maximal stimulus. In patients with renal failure, especially those with extreme hypergastrinemia, there develops the increased concentration of large, mainly biologically inactive (big big gastrin, component I) molecular forms of gastrin.

Slow continuous renal replacement therapies: an update.

Continuous renal replacement therapies (CRRT) are now being used by nephrologists, intensivists, and anesthesiologists. The various CRRT modalities differ in the kind of vascular access, the application of diffusive or convective clearances (or a combination of both), and in the location where the replacement fluid enters the circuit. CRRTs have certainly made the management of critically ill patients with acute renal failure (ARF) combined with cardiovascular instability, severe fluid overload, hypercatabolism, cerebral edema, adult respiratory distress syndrome, lactic acidosis, sepsis or other inflammatory syndromes, crush syndrome, congestive heart failure, and cardiopulmonary bypass easier. Continuous therapies incorporate several advantages including improved hemodynamic stability, optimal fluid balance, gradual urea removal, elimination of septic mediators, and the possibility of unlimited parenteral nutrition. Major difficulties and unsolved problems of CRRT are the ongoing necessity of continuous anticoagulation, considerable loss of amino acids, vitamins, trace elements, potassium, phosphate, and some drugs, as well as immobilization of the patient. The advantages of CRRT should theoretically translate into improved outcomes of critically ill ARF patients, but the superiority of continuous modalities in terms of outcome is still controversial, despite encouraging results in some clinical trials. Currently used CRRT with sophisticated treatment devices has become more expensive than hemodialysis, but the cost cannot be used as an argument against the continuous treatment modalities.

Lipid abnormalities in chronic renal failure, nephrotic syndrome and dialysis.

Cardiovascular, cerebrovascular and peripheral vascular development are the largest cause-specific reason for morbidity and mortality in end-stage renal disease (ESRD) patients. The high prevalence of cardio- and cerebrovascular death may be explained by multiple factors present in patients with progressive renal disease, including hypertension, hyperlipidemia, hyperhomocysteinemia, diabetes mellitus, and hyperparathyroidism. Experimental studies have provided in vivo and in vitro data to support the notion that lipid abnormalities contribute to glomerular and interstitial injury of the renal parenchyma. Hyperchlolesterolemia and increased low-density lipoprotein (LDL) cholesterol are prevalent in patients with the nephrotic syndrome. Plasma high-density lipoprotein (HDL) cholesterol is decreased, and reverse cholesterol transport is impaired in hemodialysis (HD) and pre-ESRD patients. Chronic renal failure patients treated with HD have an increased prevalence of intermediate-density lipoprotein (IDL), and lipoprotein(a). The findings in diabetic patients corresponded with those in nondiabetic patients with renal failure, but diabetic patients have higher apoliprotein C-III and apoliprotein E concentrations. Impaired lipid metabolism is common in patients receiving peritoneal dialysis (PD). In most ESRD patients treated with peritoneal dialysis hypercholesterolemia and hyperglyceridemia are found. Wide panels of therapeutic interventions aimed at correcting the lipid abnormalities that may develop in chronic renal patients as well as in ESRD patients are currently available. Although some novel pharmacological agents are remarkably effective in returning the lipid abnormalities to normal, there is still no convincing evidence based on long-term prospective studies, that would clearly demonstrate a significant reduction of cardiovascular morbidity and mortality of ESRD patients. The therapeutic approaches, which may be considered, include mainly dietary and life-style modifications, selective use of some technical components of dialysis systems, and the judicious prescriptions of lipid-lowering drugs.

Prescribing hemodialysis using a nomogram approach to urea kinetic modelling.

Several studies have clearly shown that the dose of dialysis is a determining factor for the well-being of dialysis patients. These studies have also suggested that doses of dialysis represented by Kt/V of about 1.4 should be optimal doses. This dose must be measured at the time it is delivered, since for various reasons, the delivered dialysis is often less than the prescribed dose. This report describes a series of nomograms that can be used to estimate the first hemodialysis prescription, to verify the amount of dialysis delivered to the patient, and to estimate the protein catabolic rate. These nomograms should be useful in those dialysis centers where, for one reason or another, computerized urea modelling is not a routine. The nomograms in the present report should be used for evaluating the adequacy of conventional hemodialysis.

Therapeutic plasma exchange in neurologic disorders.

Neurologic diseases are one of the most common indications for therapeutic plasma exchange (TPE). In autoimmune neurologic diseases like Guillain-Barre syndrome, myasthenia gravis, chronic inflammatory demyelinating polyneuropathy, and paraprotein-associated polyneuropathy, TPE has been found to be beneficial. In some others (e.g., multiple sclerosis and Eaton-Lambert syndrome), TPE cannot be considered a generally accepted treatment option.

Hepatorenal syndrome: new perspectives in pathophysiology and management.

Hepatorenal syndrome (HRS) is a unique form of acute renal failure occurring in patients with advanced liver disease. Despite the severe derangement of renal function and ominous prognosis, minimal pathologic abnormalities of the kidneys are found at autopsy. The kidneys, if transplanted, are capable of normal function, which supports the concept that renal failure is functional and potentially reversible. The pathogenesis of HRS is not completely known, but it is probably the result of an extreme underfilling of the arterial circulation secondary to an arterial vasodilation located in splanchnic circulation. Besides the renal circulation, all other extrasplanchnic vascular beds also appear to be vasoconstricted. The diagnosis of HRS is currently based on several widely accepted diagnostic criteria aimed at excluding nonfunctional causes of renal failure. Recently initiated therapeutic approaches lend a note of optimism to the future management of HRS. These include liver transplantation as definitive treatment for patients with end-stage liver disease, and introduction of new vasoconstrictor drugs with the preferential effect on the splanchnic circulation. The development of HRS after spontaneous bacterial peritonitis may be effectively prevented by the administration of albumin together with antibiotic therapy.

Hyperhomocysteinemia in end-stage renal failure.

The end-stage renal disease (ESRD) population experiences an excess morbidity and mortality due to arteriosclerotic cardiovascular disease (CVD) outcomes. Specifically, event rates for myocardial infarction and stroke are 5- to 10-fold in ESRD patients on maintenance dialysis than in the general population. Recently, there is controlled evidence that hyperhomocysteinemia occurs more commonly than any of the traditional CVD risk factors in ESRD patients. Prolonged exposure of endothelial cells to homocysteine impairs the production of nitric oxide and endothelium-dependent vasodilatation, they combine with low-density lipoprotein cholesterol to produce aggregates that are taken up by vascular macrophages in the arterial intima (foam cells), produce aggregatory effects on the platelets, and decrease endothelial antithrombotic activity due to changes in the thrombomodulin function. Current treatment regimens for ESRD hyperhomocysteinemia, which are based on the pharmacological doses of folic acid (5 to 15 mg/day), frequently result in suboptimal lowering of Hcy concentrations. Other potential therapeutic approaches (such as oral N-acetylcysteine at 1.2 g/day) merit controlled investigation.

Reprocessing and multiple use of hemodialyzers: a critical appraisal.

Economic considerations have made the reuse of hemodialyzers desirable, particularly with the introduction of expensive devices, such as large surface area or high-flux dialyzers, hemodiafilters and hemofilters. Recent studies have shown that certain reprocessing techniques confer improved biological properties on dialyzers compared with new membranes. Several investigators observed certain symptoms which occurred with greater frequency in patients receiving first use dialyzers as opposed to patients receiving dialysis treatment with reused dialyzers. Despite the potential advantages of more biocompatible membranes, and less expensive dialyzers, the safety and efficiency of reuse is the subject of some controversy. The article critically reviews the available scientific information on the risks and benefits of reprocessing.

Efficacy of therapeutic plasma exchange in specific renal disease.

Therapeutic plasma exchange (TPE) is a treatment modality used in a variety of disease states, some of which are characterized by renal involvement (i.e., primary and secondary rapidly progressive glomerulonephritis, myeloma nephropathy, thrombotic thrombocytopenic purpura, hemolytic uremic syndrome). The aim of this review was to summarize the results of clinical studies that evaluated TPE efficacy in some renal diseases, and to give general guidelines for treatment strategies in specific renal diseases.

Therapeutic plasma exchange in severe sepsis or septic shock.

Endotoxic shock with multiorgan dysfunction syndrome (MODS) is fatal in more than 80% of cases and is the leading cause of death in patients admitted to intensive care units. The incidence has increased to more then 100% in the last 10 years and there has been no significant decreases in its morbidity and mortality. The systemic inflammatory response to infection, e.g. sepsis, develops when the endotoxins activate various cascade systems. The activation of the cascade systems triggers further release of various active substances and cytokines. The progress may result in consumption coagulopathy, which may further generate an acute septic shock, disseminated intravascular coagulation, and MODS. When more than 3 organs are involved, the risk of fatal outcome exceeds 80%. The use of plasma exchange may be a beneficial adjunct to therapy during a progressive septic shock with MODS, when the patient does not respond to classical intensive care unit therapy. The beneficial effect, recently reported for plasma exchange procedures in patients with sepsis, may be due to the removal of various toxins and waste products from the blood, and administration of plasma from healthy subjects.