Search for Gamma-Ray Spectral Lines from Dark Matter Annihilation up to 100 TeV toward the Galactic Center with MAGIC.

Linelike features in TeV γ rays constitute a "smoking gun" for TeV-scale particle dark matter and new physics. Probing the Galactic Center region with ground-based Cherenkov telescopes enables the search for TeV spectral features in immediate association with a dense dark matter reservoir at a sensitivity out of reach for satellite γ-ray detectors, and direct detection and collider experiments. We report on 223 hours of observations of the Galactic Center region with the MAGIC stereoscopic telescope system reaching γ-ray energies up to 100 TeV. We improved the sensitivity to spectral lines at high energies using large-zenith-angle observations and a novel background modeling method within a maximum-likelihood analysis in the energy domain. No linelike spectral feature is found in our analysis. Therefore, we constrain the cross section for dark matter annihilation into two photons to ⟨σv⟩≲5×10^{-28} cm^{3} s^{-1} at 1 TeV and ⟨σv⟩≲1×10^{-25} cm^{3} s^{-1} at 100 TeV, achieving the best limits to date for a dark matter mass above 20 TeV and a cuspy dark matter profile at the Galactic Center. Finally, we use the derived limits for both cuspy and cored dark matter profiles to constrain supersymmetric wino models.

Teaching cardiopulmonary resuscitation using virtual reality: A randomized study.

BACKGROUND: The main functions of healthcare professionals include training and health education. In this sense, we must be able to incorporate new technologies and serious game to the teaching cardiopulmonary resuscitation. METHODS: a multicenter, comparative and cross-sectional study was carried out to assess the learning of resuscitation of a group that was trained with the use of serious gaming with virtual reality, as compared to a control group trained with conventional classroom teaching. RESULTS: the mean quality obtained in chest compressions for the virtual reality group was 86.1 % (SD 9.3), and 74.8 % (SD 9.5) for the control group [mean difference 11.3 % (95 % CI 6.6-16.0), p < 0.001]. Salivary Alpha-Amylase was 218.882 (SD 177.621) IU/L for the virtual reality group and 155.190 (SD 116.746) IU/L for the control group [mean difference 63.691 (95 % CI 122.998-4.385), p = 0.037]. CONCLUSION: using virtual reality and serious games can improve the quality parameters of chest compressions as compared to traditional training.

Modulation of incipient glomerular lesions in experimental diabetic nephropathy by hypotensive and subhypotensive dosages of an ACE inhibitor.

A glomerular permeability defect occurs early in the course of type 1 diabetes and precedes the onset of microalbuminuria and renal morphological changes. Recently, ACE inhibitors have been shown to prevent loss of glomerular membrane permselective function, but the mechanism of this nephroprotective effect is still being debated. The objective of the present study was to evaluate the effects of hypotensive and subhypotensive dosages of the ACE inhibitor quinapril ex vivo and of its active metabolite quinaprilat in vitro on the glomerular albumin permeability (P(alb)) defect in the early phases of experimental diabetes. For the ex vivo study, six groups of male Wistar rats were evaluated for 4 weeks. One group served as a nondiabetic control (C); the other five groups were rendered diabetic and included untreated diabetic rats (D) and diabetic rats receiving quinapril at the dosages of 5 (DQ1), 2.5 (DQ2), 1.25 (DQ3), and 0.625 (DQ4) mg. kg(-1). day(-1). Dosage-dependent effects of quinapril on systolic blood pressure and the glomerular filtration rate were observed. In contrast, control of P(alb) in isolated glomeruli exposed to oncotic gradients, proteinuria, and glomerular and tubular hypertrophy was obtained with subhypotensive dosages (DQ3 and DQ4 groups) of the ACE inhibitor. In the in vitro study, quinaprilat reduced P(alb) significantly in concentration ranges from 10(-6) to 10(-14) mol/l compared with results in control glomeruli. The effect on P(alb) may have occurred by mechanisms different from kidney ACE inhibitor. These study results indicated that ACE inhibitor treatment prevents the early onset of the P(alb) defect in experimental diabetes. This effect seemed to occur independently of systemic or glomerular hemodynamic changes and, at least partially, from kidney ACE inhibition.

[Arterial hypertension and sleep apnea hypopnea syndrome in primary care]. / Hipertensión arterial y síndrome de apneas-hipoapneas del sueño en atención primaria.

INTRODUCTION AND OBJECTIVES: Sleep apnea hypopnea syndrome (SAHS) is frequent in hypertensive patients and plays a role in a greater incidence of cardiovascular morbidity-mortality. This study aims to know the clinical profile of hypertensive patients with SAHS compared to hypertensive patients without SAHS to know which variables should be used to orient their screening from primary care. METHODOLOGY: An observational, descriptive, retrospective study of cases (hypertensive patients with SAHS) and controls (hypertensive patients without) was performed in an urban health care center. Based on a computerized registry of the site, patients diagnosed of SAHS and hypertension over 30 years of age were selected. For each case, one control case of hypertensive patients without SAHS paired by age and gender was randomly obtained. RESULTS: A total of 64 cases and 64 controls were selected. Standing out in the bivariate analysis were greater BMI (34.3±12.8 vs. 28.6±3.6), predominance of obesity (70.3 vs. 35.9%), metabolic syndrome (77.3 vs. 42.2%), consumption of psychopharmaceuticals (19.7 vs. 7.8%) and anithypertensive drugs (26.5 vs. 14.0%), ischemic heart disease (20.3 vs. 9.4%) in the case group versus control group (P<.05 for all the variables). The multivariate analysis showed that only the presence of metabolic syndrome was related with the presence of SAHS in hypertensive patients (OR 4.65; 95% CI: 2.03-10.64; P<.001). CONCLUSIONS: Screening for SAHS should be performed in hypertensive patients seen in primary care if they have metabolic syndrome criteria.

Recurrent focal glomerulosclerosis: natural history and response to therapy.

PURPOSE: Recurrent focal glomerulosclerosis (FGS) has been well documented since it was first reported in 1972. However, the course of the disease after transplantation and the optimal treatment regimen have not been well defined since the introduction of newer treatment modalities. PATIENTS AND METHODS: We reviewed all the charts of patients with biospy-proven FGS who received renal transplants at our institution from January 1980 through December 1990. Case histories consistent with diagnoses other than primary FGS (such as reflux nephropathy or intravenous drug use) were eliminated from the study. During this time period, 78 allografts were received by 71 patients with FGS. Independent variables that were analyzed included sex, race, time in months between the diagnosis of FGS and end-stage disease (dialysis or transplantation), age at time of transplantation, type of dialysis, source of allograft (cadaveric or living related), haplotype matching, donor-specific transfusions, age and sex of the donor, post-transplantation acute tubular necrosis, rejection episodes, immunosuppression regimen, use of plasmapheresis and angiotensin converting enzyme (ACE) inhibitors, and outcome. RESULTS: FGS recurred in 25 allografts (32%) of 21 patients. Biopsy-proven diagnosis of recurrence was made a mean of 7.5 months (range: 0.5 to 44 months) after transplantation. Patients who had rapid progression to end-stage disease tended to experience more frequent recurrences. Of seven patients who received a second transplant, five patients lost the first graft to recurrent FGS, and four of those patients (80%) had a recurrence in the second allograft. Recurrent disease developed in 34% of patients concurrently treated with cyclosporine and in 28% of those treated with prednisone and azathioprine alone (NS). Patients with recurrent FGS who were treated with ACE inhibitors benefited from a significant reduction of proteinuria. Six patients underwent plasmapheresis after diagnosis of the recurrence. Three of five patients in whom the diagnosis was made early in the course of the disease and in whom plasmapheresis was initiated immediately had reversal of epithelial foot process effacement and remission of proteinuria. End-stage disease eventually developed in 14 allografts (56%) an average of 23.7 months (range: 1 to 65 months) after diagnosis of recurrent disease. The cause of failure was chronic rejection in four allografts and recurrent disease in the remaining 10 allografts. CONCLUSIONS: FGS recurs in approximately 30% of allografts and causes graft loss in half of these. Patients who have lost a first allograft to recurrent FGS are at high risk for developing recurrent disease in a second allograft. Prolonged allograft survival is possible in patients with recurrent FGS and may best be obtained with a combination of treatment modalities including cyclosporine (perhaps in higher dosages than are routinely used in clinical renal transplantation), ACE inhibitors, and early use of plasmapheresis. The efficacy of these modalities supports the notion that recurrent FGS is caused by a circulating humoral mediator.

Prediction and treatment of recurrent focal segmental glomerulosclerosis after renal transplantation in children.

The recurrence of focal segmental glomerulosclerosis (FSGS) after renal transplantation has a potentially detrimental course toward the loss of renal function. To identify prognostic markers for recurrence and efficacy of treatment, we evaluated the outcome of 32 renal allografts in 29 pediatric patients with FSGS who underwent transplantation from 1987 to 1998 in the North Italy Transplant program. Recurrence was observed in 15 of 29 patients (52%) after the first transplant and in 3 of 3 patients (100%) after the second graft. No significant differences in sex, age at FSGS onset, age at transplantation, or length of dialysis were noted between patients with recurrent and nonrecurrent FSGS. Those with recurrence originally developed end-stage renal failure faster (3.9 years) than those without recurrence (6.2 years). Pretransplantation serum samples from 25 patients were tested in an in vitro assay that evaluates glomerular permeability to albumin. FSGS recurred in 11 of 13 children who tested positive for the permeability factor and in 4 of 12 patients with a negative test result; the odds ratio for developing recurrence was 10.99 (95% confidence limit, 1.6 to 75.47) in the former group. The immediate onset of proteinuria after transplantation was a negative prognostic factor for the outcome; 6 of 9 patients in whom proteinuria appeared within 2 days of transplantation returned to dialysis in less than 24 months. In 9 of 11 patients who were treated with plasmapheresis plus cyclophosphamide after recurrence, proteinuria was successfully reversed and persistent remission was obtained in 7 patients. These data show that the glomerular permeability test has a significant predictive value for the recurrence of proteinuria in children with FSGS who have received a renal allograft. Of the clinical parameters considered, only the duration of disease was significantly different in patients with recurrent versus nonrecurrent FSGS. Treatment with plasmapheresis plus cyclophosphamide can be effective in the control of FSGS relapse after renal transplantation.

Serum and intracellular magnesium concentrations in intoxicated chronic alcoholic and control subjects.

Serum magnesium levels may not accurately reflect overall magnesium homeostasis. To clarify the relationship between serum and intracellular magnesium concentrations in chronic alcoholism, we determined intralymphocytic magnesium levels and serum magnesium, sodium and potassium concentrations in ten chronic alcoholic subjects admitted to the emergency room during acute ethanol intoxication, and compared the results to those of 14 healthy nonalcoholic controls. Serum magnesium, sodium and potassium concentrations were within the normal range in both groups of subjects and determination of intralymphocytic magnesium levels revealed a nonsignificant decrease in alcoholic subjects compared to controls. In conclusion, serum and intralymphocytic magnesium concentrations did not differ between chronic alcoholics and controls in our population; the results of the present study do not support the practice of routine magnesium administration to chronic alcoholics in the emergency room setting.

Humoral permeability factors in the nephrotic syndrome: a compendium and prospectus.

The concept that increased glomerular albumin permeability in steroid-resistant nephrotic syndrome is induced by circulating humoral factors is not new. Zimmermann (1) was among the first to demonstrate that serum from a renal transplant patient with recurrent focal segmental glomerulosclerosis (FSGS) could provoke increased albumin excretion when infused in the aorta of intact rats. Unfortunately, the experiment was not easily reproducible, and the possibility that human serum could induce serum sickness in rats was a serious limitation of the original experiment. We now know that inhibitors of permeability activity are present in both normal human and rat serum (see below), which explains the difficulty in replicating the disease in intact animals. In 1974 Shalhoub (2) theorized that a disordered clone of T lymphocytes, present in both minimal change disease and FSGS, secreted a circulating lymphokine "toxic" to the glomerular barrier. In support of this hypothesis, Koyama et al (3) formed hybridomas from T cells from four patients with minimal change disease and three control subjects. The hybridomas of the patients produced a substance that induced proteinuria when injected intravenously into normal rats. However, the study utilized stimulated and not quiescent T cells, and therefore the relevance to the pathogenesis of FSGS is unknown. Hoyer and colleagues first described recurrence of idiopathic nephrotic syndrome after renal transplantation in 1972 (4). Numerous subsequent reports have established the rate of recurrence as being about 30%. Timely plasmapheresis associated with aggressive immunosuppression resolves the proteinuria and disease progression in a large proportion of cases (5). FSGS not only recurs after renal transplantation, but the diseased kidney can also recover when kept protected from the pathological milieu. Rea et al (6) demonstrated that kidneys from a donor with FSGS transplanted into two uremic recipients were free from proteinuria, and that renal function was normal after one year. Ethical and legal considerations aside, recurrence of FSGS after transplantation is strong evidence supporting the role of a humoral factor in the pathogenesis of the disease.

Apheresis in primary focal segmental glomerulosclerosis of native and transplanted kidneys: a therapeutic protocol.

BACKGROUND: Patients with focal segmental glomerulosclerosis (FSGS) develop nephrotic syndrome and terminal renal failure in most cases. FSGS reappears in 15-50% of transplanted kidneys and frequently causes the graft loss. Sera from patients with FSGS of native or transplanted kidneys contain some proteinuric or permeability factors (PF) which can be removed by means of plasma exchange (PE) or protein A Immunoadsorption (IA). METHODS: We suggest a therapeutic protocol, for patients with biopsy proven FSGS of native or transplanted kidneys, resistant to steroid and immunosuppressive therapy, based on the association of PE or IA to conventional drug therapy. Daily proteinuria, renal function, serum albumin and circulating level of proteinuric factors (permeability test) will be monitored at regular time intervals during the apheresis cycle, which will be intensive at the beginning (8-10 sessions in 4 weeks) and very gradually discontinued. Results. We will consider satisfactory remission the reduction of proteinuria below 1 g/day, improvement of renal function, normalization of serum albumin level (> 3.5 g/dl). Partial remission will be considered: proteinuria below 3 g/day, stable renal function, serum albumin level between 3 and 3.5 g/dl. Permeability test, if positive at baseline examination, should be negative after apheresis. CONCLUSIONS: The primary endpoint of our protocol is: lasting remission (satisfactory or partial) after the apheresis suspension. Secondary endpoints are: maintained remission with continuing apheresis sessions, correlation between permeability activity and disease activity, identification of responders and non responders patients on the basis of positive permeability test.

Longitudinal study of phenobarbital in serum, cerebrospinal fluid, and saliva in the dog.

Serial assays for phenobarbital were done on the blood serum, cerebrospinal fluid (CSF), and saliva from three epileptic and two clinically normal dogs that were given various oral doses of the drug. In all dogs, the three fluids showed considerable daily fluctuations of phenobarbital concentrations, even after several weeks at the same dosage. The average ratio for CSF/serum was 0.53 and 0.39 for saliva/serum. A highly significant (P less than 0.001) correlation coefficient occurred between CSF and serum (0.95) and between CSF and saliva (0.93); although in some dogs at particular dosages, the CSF and saliva were poorly correlated. Dose-related curves demonstrated a gradually increased phenobarbital concentration in the three fluids up to dosages of 9.0 mg/kg of body weight. The present study suggests that multiple serum or saliva samples should be assayed to account for daily fluctuations; saliva can be a good indicator of unbound phenobarbital concentration in CSF.

[Odynophagia, fever and rash in a 33 year-old woman]. / Odinofagia, fiebre y exantema en mujer de 33 años.

Hand-Foot-Mouth disease is a viral exanthematous disease primarily caused by Coxsackie virus that mainly affects children under 10 years-old during the spring or summer. It is a rare disease in adults, and rarer still in the immunocompetent. We report the case of a 33-year-old immunocompetent adult affected bys Hand Foot Mouth disease.

Unanticipated discovery of vascular anomalies by hemodialysis catheter placement. Case report.

This case report describes an unexpected finding post hemodialysis catheter placement in a child scheduled for living-relation renal transplant. Moreover, the unusual appearance of the catheter on a chest X-ray prompted further investigation of the patient's vascular anatomy, resulting in the discovery of an aberrant iliac artery course that significantly affected the surgical approach to this planned procedure.

Dose effect of nitrendipine on urinary enzymes and microproteins following non-ionic radiocontrast administration.

BACKGROUND: Although calcium-channel antagonists have been proposed as prophylaxis to prevent radiocontrast-induced nephropathy, the dose and dose interval to achieve a protective effect have not been quantified in humans. METHODS: In a randomized, double-blind protocol we studied urinary enzyme and microprotein excretion in 121 outpatients (mean age 65.3 +/- 9.3 years, 62% male) with normal renal function who were to undergo digital subtraction arteriography with iohexol or iopentol. The subjects were treated with a single dose of placebo (group 1) or nitrendipine 10 mg (group 2) or 20 mg (group 3) p.o. 1 h before the procedure. Blood and urine samples were collected 1 h before, 1 h after, and 24 h after contrast administration. Study variables included contrast volume and serum creatinine, and urinary creatinine, osmolality, albumin, alanylamino-peptidase (AAP, a brush border enzyme), N-acetyl-beta-glucosaminidase (NAG, a lysosomal enzyme), and alpha-1-microglobulin (alpha-1-micro, a filtered microprotein). RESULTS: Serum values of creatinine remained unchanged during the study period. Albuminuria was not affected by contrast administration, whereas AAP, NAG, and alpha-1-micro increased significantly, all except AAP returning to baseline at 24 h. Pretreatment with nitrendipine did not reduce enzyme excretion, although AAP levels were lower in general in the group assigned to the 20-mg dose. Acute renal failure, defined as a 50% increase of serum creatinine 24 h after radiocontrast administration, was found in eight patients: four from group 1 (8.3%), three from group 2 (6.5%), and one from group 3 (3.7%). CONCLUSIONS: Neither the course of enzyme excretion nor the incidence of acute renal failure following radiocontrast administration were affected by single doses of calcium antagonists. AAP levels were lower in general in subjects taking the 20-mg dose of nitrendipine. This study also indicates that a single low or normal dose of nitrendipine per os is not effective prophylaxis before radiocontrast administration. The designs of future studies investigating the "nephroprotective' effect of calcium-channel antagonists per os should incorporate (1) the use of repeated doses to saturate hepatic metabolic pathways, and (2) the control of confounding variables in the measurement of urinary enzymes.

Plasmapheresis reduces proteinuria and serum capacity to injure glomeruli in patients with recurrent focal glomerulosclerosis.

To test the hypothesis that a circulating mediator is associated with recurrent idiopathic focal glomerulosclerosis (FGS), we studied the effect of plasmapheresis on reducing proteinuria in patients with the disease. An in vitro assay measured the capacity of sera before and after plasmapheresis to cause increased albumin permeability (P(albumin)++) in isolated rat glomeruli. Nine patients (five males aged 2 to 66 years) who underwent plasmapheresis for recurrent FGS were identified. Study variables included age, sex, time from diagnosis of recurrence to first pheresis, glomerular hyalinosis, complications, outcome, and proteinuria before and after plasmapheresis. Rat glomeruli were isolated in medium containing 4 g/dL bovine serum albumin, and P(albumin) was determined from the change in glomerular volume in response to an albumin gradient after incubation of the glomeruli in a 1:50 dilution of patient serum. Plasmapheresis reduced proteinuria from a mean of 12 +/- 7.46 g/24 hr to 5.1 +/- 7.39 g/24 hr (P = 0.03). Six patients in whom the diagnosis was made early in the course of the disease and in whom plasmapheresis was initiated immediately had lasting remissions. Preplasmapheresis biopsies in the patients who did not achieve remissions showed both epithelial foot process effacement and glomerular sclerosis. Serum samples were available from four patients for albumin testing in vitro. P(albumin)++ was reduced from a mean of 0.76 +/- 0.17 before pheresis to 0.18 +/- 0.31 after (P = 0.07). Therefore, the mechanism by which plasmapheresis reduces proteinuria in patients with recurrent FGS involves the decreased capacity of sera from these patients to injure the glomerular permeability barrier.(ABSTRACT TRUNCATED AT 250 WORDS)

Nifedipine reduces postexercise proteinuria in young volunteers.

Previous studies have demonstrated that it is possible to prevent postexercise proteinuria with angiotensin-converting enzyme inhibitors. To determine whether calcium antagonists have the same effect, 40 young healthy volunteers underwent maximal aerobic exercise with and without nifedipine 10 mg per os 1 h before the first or second trial. Urinary excretion of albumin (UAE), transferrin (UTE) and alpha 1-microglobulin (UME) were examined before and after each trial. UAE, UTE and UME were significantly increased after exercise. Nifedipine significantly decreased UAE (p = 0.001) and UTE (p = 0.02) after exercise, and slightly decreased the maximal work load and the basal excretion of albumin. UME was unchanged. Therefore, the results of this study demonstrate that nifedipine administration before exercise significantly reduces postexercise proteinuria.

Albumin permeability in isolated glomeruli in incipient experimental diabetes mellitus.

AIMS/HYPOTHESIS: The pre-clinical phase of diabetic nephropathy is characterised by increased glomerular filtration rate and episodes of microalbuminuria. The cause of the microalbuminuria has been variably ascribed to alterations of the size or charge selective barriers of the glomerulus or both or as a consequence of the haemodynamic changes. Our aim was to investigate very early albumin permeability alterations in isolated glomeruli which were not subject to perfusion pressure. METHODS: Isolated glomeruli were studied from 120 male Wistar rats, divided into three groups: streptozotocin-treated, streptozotocin-treated with insulin pellet implants, and controls. From each group ten animals were killed at 7, 14, 28, and 56 days after induction. Study variables included blood pressure, proteinuria, iopamidol clearance, albumin permeability and glomerular area. Subsequently, albumin permeability, proteinuria, and iopamidol clearance were determined in an additional group of 40 diabetic animals studied at 24, 72, 96, and 120 h after induction. RESULTS: Albumin permeability increased steadily from induction in streptozotocin-treated animals, reaching a plateau at approximately 120 h. Glomerular filtration rate was shown to increase significantly at approximately 7 days and proteinuria correlated with it. Glomerular hypertrophy was observed both in streptozotocin-treated animals and in streptozotocin-treated rats with insulin pellet implants. Strict blood glucose control delayed the appearance of the permeability defect in isolated glomeruli and inhibited the increase in glomerular filtration in intact animals. It did not prevent glomerular hypertrophy. CONCLUSION/INTERPRETATION: An albumin permeability defect exists early in isolated non-perfused glomeruli from streptozotocin-treated rats and seems to be independent of glomerular filtration rate alterations.

Inhibitory effect of Tripterygium wilfordii multiglycoside on increased glomerular albumin permeability in vitro.

BACKGROUND: Tripterygium wilfordii Hook F is a medicinal plant used for the treatment of glomerulonephritis in China. We studied the effect of Tripterygium wilfordii multiglycoside (TWG) on glomerular albumin permeability (Palbumin) in vitro. METHODS: Isolated rat glomeruli were incubated with protamine (600 micrograms/ml) for 30 min, or with human recombinant tumour necrosis factor (TNF-alpha 0.4 ng/ml), superoxide (10 units/ml), or serum from a focal segmental glomerular sclerosis (FSGS) patient for 10 min at 37 degrees C. TWG, 1 mg/ml, was added in parallel tubes to study the effect on Palbumin. Control glomeruli were incubated under identical conditions. The albumin reflection coefficient (sigma albumin) was calculated from the change in glomerular volume in response to an applied oncotic gradient. Convectional permeability (Palbumin) was calculated as (1 - sigma albumin). RESULTS: Compared with controls, protamine increased the Palbumin of glomeruli (0.83 +/- 0.05, n = 25, vs 0.18 +/- 0.03, n = 20); pretreatment with TWG blocked this effect (0.13 +/- 0.04, n = 25). TNF-alpha also increased the Palbumin (0.79 +/- 0.04, n = 24 vs 0.04 +/- 0.07, n = 19); preincubation with TWG blocked this effect (0.03 +/- 0.09, n = 24). Palbumin of glomeruli incubated with xanthine and xanthine oxidase, resulting in the production of superoxide, also increased as compared to controls (0.85 +/- 0.04, n = 15 vs 0.08 +/- 0.05, n = 14); TWG blocked this effect as well (0.21 +/- 0.08, n = 14). FSGS serum also increased Palbumin of glomeruli significantly (0.88 +/- 0.02, n = 49 vs 0.00 +/- 0.02, n = 49); preincubation with TWG blocked this effect (0.05 +/- 0.07, n = 30). TWG by itself had no effect on Palbumin (0.19 +/- 0.10, n = 15). CONCLUSIONS: Our results show that TWG blocks protamine, TNF-alpha, superoxide, and FSGS serum-mediated increase in glomerular albumin permeability in vitro. We conclude that reduction of proteinuria by Tripterygium wilfordii multiglycoside in various kinds of glomerular diseases in vivo might be due to protection of the glomerular filtration barrier.

[A comparison between an ionic paramagnetic contrast agent (Gd-DTPA) and a nonionic one (Gd-DTPA-BMA) in functional kidney evaluation with magnetic resonance]. / Confronto tra un mezzo di contrasto paramagnetico ionico (Gd-DTPA) e uno non ionico (Gd-DTPA-BMA) nella valutazione funzionale del rene con Risonanza Magnetica.

INTRODUCTION: The combination of TGE sequences with bolus injection of paramagnetic contrast agents permits to study renal function and perfusion. We studied renal function with both an ionic (Gd-DTPA) and a nonionic paramagnetic contrast agent (Gd-DTPA-BMA) to compare their kinetics in normal kidneys. MATERIAL AND METHODS: Twenty MR examinations were performed on 20 subjects with normal renal function. Ten subjects were examined after i.v. injection of Gd-DTPA and the other ten subjects after i.v. injection of Gd-DTPA-BMA. MR examinations were performed on a Philips ACS II unit (1.5 T). Two sequences were acquired in all cases; an SE coronal T1-weighted sequence (TR/TE = 600/19 ms) and a TGE coronal T1-weighted sequence (TR/TE = 12/5 ms, flip angle = 25 degrees) performed after bolus injection of the contrast agent at 0.1 mmol/kg. Signal intensity time curves were obtained in all the cases. The signal intensity of the cortex, corticomedullary junction, medulla and the pyelocaliceal system of each kidney was measured using a region of interest (ROI). Signal intensity curves were analyzed considering some quantitative parameters such as the area under the curve (AUC), the peak (P) and the time to peak (T-P). RESULTS: In the subjects with normal renal function, four phases were demonstrated after the i.v. injection of either Gd-DTPA or Gd-DTPA-BMA, namely the cortical phase, the cortico-medullary junction phase, the medullary phase and the pyelocaliceal system phase. No statistically significant differences between the two agents were demonstrated in signal intensity time curves and quantitative parameters. CONCLUSIONS: Gd-DTPA and Gd-DTPA-BMA showed the same efficacy in renal function studies.

[Morpho-functional study of the kidney in patients with kidney disease and liver disease with magnetic resonance]. / Studio morfo-funzionale del rene nei pazienti nefropatici e nei pazienti epatopatici con Risonanza Magnetica.

INTRODUCTION: We studied renal function and perfusion after the i.v. injection of Gd-DTPA-BMA, a nonionic paramagnetic contrast agent, to assess renal morphology and function in normal subjects, in renal insufficiency patients and in patients with hepatic failure and normal renal function. The latter were chosen because some patients with advanced hepatic failure may suffer from the hepatorenal syndrome, characterized by severe vasoconstriction in the renal cortical vessels. We investigated if dynamic MRI can detect early renal perfusion abnormalities in the patients who will eventually develop this syndrome. MATERIAL AND METHODS: Thirty MR examinations were carried out on 30 subjects after the i.v. injection of Gd-DTPA-BMA. Our series consisted of: 10 normal subjects; 10 renal insufficiency patients; 10 patients with hepatic failure and normal renal function. MR examinations were performed on a Philips ACS II scanner operating at 1.5 T. Two sequences were carried out in all cases: T1-weighted SE and T1-weighted TGE sequences after the bolus injection of .1 mmol/kg contrast agent. Renal longitudinal diameter and parenchymal thickness were measured in all cases and signal intensity time curves were always made. The signal intensity of the cortex, corticomedullary junction, medulla and pyelocaliceal system of each kidney was measured using a region of interest (ROI). The signal intensity curves were made considering quantitative parameters, including the area below the curve (ASC), the peak (P) and the time to peak (T-P). RESULTS: Longitudinal diameter and parenchymal thickness values were significantly lower in renal insufficiency patients than in normal subjects. Four phases were demonstrated after i.v. contrast agent injection in normal subjects, namely A) the cortical phase, B) the corticomedullary junction phase, C) the medullary phase, D) the pyelocaliceal phase. No signal intensity decrease in the medullary and pyelocaliceal curves was observed in renal insufficiency patients. Signal intensity curves values were lower in hepatic failure patients than in those with normal renal function. Hepatic failure patients could be divided into two groups: 5 patients had low P and ASC values and 4 had normal P and ASC values. The patients with lower P and ASC values developed the hepatorenal syndrome within a few months of the MR examination. DISCUSSION: Signal intensity decreased in the pyelocaliceal system phase in normal subjects because of the high paramagnetic contrast agent concentration. The lack of signal intensity decrease in renal insufficiency patients was caused by the reduced capability of concentrating Gd-DTPA-BMA. Lower signal intensity values in hepatic failure patients may be considered an early sign of the hepatorenal syndrome.

Inhibition of renal permeability towards albumin: a new function of apolipoproteins with possible pathogenetic relevance in focal glomerulosclerosis.

Focal segmental glomerulosclerosis (FSGS) is a degenerative renal disease characterized by the accumulation of extracellular matrix and lipids within the glomerular tuft. It has been proposed that an abnormal renal permeabilization towards proteins induced by a putative plasma factor is, in some way, involved in the pathogenesis of the disease. In this paper, we measured the plasma permeability activity (Palb) in several sera of patients with FSGS and found a mean activity of 0.82+/-0.03 which means a marked increase compared to a mean Palb of 0.16+/-0.03 in normal controls. Coincubation of FSGS and normal serum reduced the permeability activity within the normal range; normal serum added to the incubation medium after the glomeruli had already been exposed to the FSGS serum had no effect, suggesting the presence of inhibitory substances with a direct effect on a circulating substrate. Finally, the antipermeability activity was retained when heated to 60 degrees C but not to 100 degrees C. By serial fractionations of normal serum and reported activity measurements at each step, five natural occurring inhibitors of albumin permeabilization were purified and characterized by matrix assisted laser desorption/ionization-mass spectrometry (MALDI-MS), as components of apolipoproteins (apo) (apo E2 and E4, apo L, the high Mr apo J and a 28 kDa fragment of apo A-IV). Coincubation of each apolipoprotein with FSGS serum inhibited permeability, but only apo J and apo E2 and E4 were found to be crucial for the process. In conclusion, we have purified from normal serum five inhibitors of permeability induced by FSGS serum, all corresponding to apolipoproteins. An imbalance between permeability factors and apolipoproteins may play a pathogenetic role in FSGS.