Alemtuzumab significantly improves posterior fossa syndrome presented as a relapse of multiple sclerosis.

BACKGROUND: Posterior fossa syndrome (PFS) is a rare manifestation of ponto-mesencephalic lesions frequently reported in post-surgical pediatric tumors, rarely described as a consequence of vascular, infective or inflammatory lesions. OBJECTIVE: The aim of this article is to report the clinical and neuroradiological characteristics of a patient with an acute PFS presentation as a relapse in relapsing-remitting MS, significantly responsive to Alemtuzumab treatment. CASE REPORT: 24-year-old patient affected by multiple sclerosis developed motor-cognitive and behavioral syndrome related to an extensive ponto-mesencephalic lesion under Fingolimod treatment. CONCLUSION: Our case highlights the significant and rapid effect of Alemtuzumab therapy on both cognitive and motor symptoms occurring during a MS relapse with atypical neuroradiological localization.

Early markers of Fabry disease revealed by proteomics.

Fabry disease (FD) is an X-linked lysosomal storage disorder caused by a deficiency of the lysosomal hydrolase α-galactosidase A (α-GalA) that leads to the intra-lysosomal accumulation of globotriaosylceramide (Gb3) in various organ systems. As a consequence, a multisystems disorder develops, culminating in stroke, progressive renal and cardiac dysfunction. Enzyme replacement therapy (ERT) offers a specific treatment for patients affected by FD, though the monitoring of treatment is hindered by a lack of surrogate markers of response. Remarkably, due to the high heterogeneity of the Fabry phenotype, both diagnostic testing and treatment decisions are more challenging in females than in males; thus, reliable biomarkers for Fabry disease are needed, particularly for female patients. Here, we use a proteomic approach for the identification of disease-associated markers that can be used for the early diagnosis of FD as well as for monitoring the effectiveness of ERT. Our data show that the urinary proteome of Fabry naïve patients is different from that of normal subjects. In addition, biological pathways mainly affected by FD are related to immune response, inflammation, and energetic metabolism. In particular, the up-regulation of uromodulin, prostaglandin H2 d-isomerase and prosaposin in the urine of FD patients was demonstrated; these proteins might be involved in kidney damage at the tubular level, inflammation and immune response. Furthermore, comparing the expression of these proteins in Fabry patients before and after ERT treatment, a decrease of their concentration was observed, thus demonstrating the correlation between the identified markers and the effectiveness of the pharmacological treatment.

[Survival is not enough: improving quality of life]. / Sopravvivere non basta--migliorare la qualità della vita.

We need a new health care system that is based on patients' needs. The present cadre of health managers who acquired power by cutting expenditures must be removed from office. We need to educate a new cadre of health managers who are 1) convinced that safeguarding health does not use up the resources of the next generations; 2) capable of switching the system from curative to preventive medicine; and 3) able to reinforce clinical research. Such principles have been recently adopted by the French President Sarkozy in devising the national health care program.

Sevelamer worsens metabolic acidosis in hemodialysis patients.

BACKGROUND: Sevelamer hydrochloride, a major phosphate binder for patients on maintenance hemodialysis (MHD) is associated with reduced serum bicarbonate concentration due to hydrochloric acid release in the gut and to the binding of short chain fatty acids in the large intestine. Since metabolic acidosis can be deleterious, a study was devised to compare the time course of serum bicarbonate concentration during treatment with sevelamer hydrochloride or calcium carbonate. METHODS: Sixteen well nourished patients on MHD who were in excellent clinical conditions and achieving target levels for blood pressure (BP) and hemoglobin (Hb), while on a protein intake of 1.1g/kg body weight (bw), were enrolled in the study. After a 2-week washout period, the patients were divided into two groups, each consisting of eight patients, and randomized either to 24 weeks of sevelamer followed by 24 weeks of calcium carbonate (group A) or to 24 weeks of calcium carbonate followed by 24 weeks of sevelamer (group B). Protein intake, n-protein catabolic rate (nPCR), serum concentrations of calcium, phosphate, calcium x phosphate (Ca x P) product, bicarbonate, intact parathyroid hormone (iPTH) and albumin were monitored. Time course changes in serum bicarbonate concentrations in relation to short and long dialytic intervals (48 vs. 72 hr) were also investigated. RESULTS: Both sevelamer and calcium carbonate effectively controlled serum phosphate and the Ca x P product. During calcium carbonate treatment plasma phosphate concentrations were significantly below those of patients on sevelamer. Plasma bicarbonate concentration fell within target DOQI values during calcium carbonate administration both in group A and in group B, a goal which was not achieved under sevelamer administration. After a long dialytic interval in patients on sevelamer, serum bicarbonate concentration averaged 17.3 +/- 1.1 mEq/L, whereas it averaged 21.1 +/- 0.7 mEq/L in patients on calcium carbonate (p<0.01). Finally, a 24-week sevelamer administration caused a statistically significant (p<0.05) reduction (0.8 g/dL) in serum albumin concentration, without affecting iPTH. Taken together, these results indicate that sevelamer worsens metabolic acidosis, which needs to be corrected.

Acid-base balance in heart failure.

In end-stage heart failure, various acid-base disorders can be discovered due to the renal loss of hydrogen ions and hydrogen ion movements into cells, the reduction of the effective circulating volume, hypoxemia and renal failure. This justifies the occurrence of metabolic alkalosis, metabolic acidosis, respiratory alkalosis, as well as respiratory acidosis alone or in combination. Several studies have been published on the acid-base state in heart failure. In a 1951 study, Squires et al analyzed the distribution of body fluid in congestive heart failure by taking into consideration the abnormalities in serum electrolyte concentration and in acid-base equilibrium. A recent study by Milionis et al, analyzed 86 patients with congestive heart failure receiving conventional treatment; the majority of these patients exhibited hypokalemia, hyponatremia, hypocalcemia and hypophosphatemia. Disorders in acid-base balance were noted in 37.2% of patients. In a recent study, 70 patients with severe congestive heart failure before heart transplantation showed high-normal pH, slightly reduced pCO 2 and a slight loss of hydrogen ions. After heart transplantation, stability of blood pH and hydrogen ion concentrations was found. In contrast, bicarbonate and pCO 2 increased significantly. The data led us to formulate the diagnosis of a mixed acid-base disorder that includes respiratory alkalosis and metabolic alkalosis before heart transplantation. In heart failure, the presence of acid-base imbalance associated with the activation of mechanisms that lead to salt and water retention reveals evidence concerning the pivotal role of the kidney in determining the outcome of these patients.

[Guidelines on water and solutions for dialysis. Italian Society of Nephrology]. / Linee Guida su acque e soluzioni per dialisi.

The National Society of Nephrology has promoted the development of specific Italian Guidelines for dialysis fluids. Two previous national inquiries showed a wide variety in the type and frequency of both microbiological and chemical controls concerning dialysis water, reinforcing the need for specific standards and recommendations. An optimal water treatment system should include tap water pre-treatment and a double reverse osmosis process. Every component of the system, including the delivery of the treated water to the dialysis machines, should prevent microbiological contamination of the fluid. Regular chemical and microbiological tests and regular disinfection of the system are necessary. 1. Chemical quality (Table: see text). Treated tap water used to prepare dialysis fluid should be within European Pharmacopoeia limits at the water treatment system inlet and at the reverse osmosis outlet. In addition dialysate, concentrate and infusion fluids must comply with specific Pharmacopoeia limits. The physician in charge of the dialysis unit is advised to institute a multidisciplinary team to evaluate the requirement for added chemical controls in the presence of local hazards. 2. Microbiological quality (Table: see text). High microbiological purity of dialysis fluid--regularly verified--is a fundamental prerequisite for dialysis quality and every dialysis unit should aim as a matter of course to obtain "ultra-pure" dialysate (microbial count <0.1 UFC/mL, endotoxins <0.03 U/mL). On-line dialysate ultrafiltration and regular disinfection of dialysis machines greatly enhance microbiological purity. On-line dialysate reinfusion requires specific devices used according to corresponding instructions and to more frequent microbiological tests. Dialysis fluids for home dialysis should comply with the same chemical and bacteriological quality. The appendix reports the water treatment system's technical characteristics, sampling and analytical methods, monitoring time-tables, as well as the origin and effects of the main toxic substances. Suggestions and questions concerning these guidelines are welcome to nefrologia@sin-italy.org.

The heart in uremia: role of hypertension, hypotension, and sleep apnea.

Cardiovascular disease is the leading cause of morbidity and mortality in end-stage renal disease. Causes include those usually found in the general population, those related to the uremic status, and those related to dialytic treatment. Hypertension, hypotension, anemia, hypoalbuminemia, malnutrition, dyslipidemia, reactive C protein, calcium-phosphate product, dialysis modalities, and hyperhomocysteinemia are discussed extensively. Special emphasis is put on hyperparathyroidism as a traditional toxin. The emergent role of sleep apnea has been confirmed in animal models as well as in humans studied using polysomnography. There are difficulties in diagnosing coronary disease, because angiography is not risk-free, is expensive, and should be reserved for patients having symptoms of heart failure and/or patients having diabetes mellitus, and/or patients entering a transplantation list. This allows patients with coronary disease to undergo coronary artery bypass (preferably) or percutaneous transluminal angioplasty. Patients for whom surgery is not appropriate should be treated using more traditional medical procedures.

Renal abscess: recovery without hospitalization and drainage.

BACKGROUND: Renal absceeses in childhood are rare and require hospitalization, antibiotic therapy and drainage. PATIENTS: Two cases of renal abscess in childhood are described. In both cases there was no history of either antecedent skin infection or urinary tract infection or reflux. Flank pain and fever had a sudden onset. RESULTS: The diagnosis was made in the first case by ultrasound and gadolinium-enhnaced magnetic resonance, in the second case ultrasound and computerized axial tomography were used. The patients were successfully treated at home with antibiotic therapy but without drainage. CONCLUSION: Renal abscesses must be suspected in children with loin pain, fever and leukocytosis. They may heal even without hospitalization and drainage.

Level of hydration and renal function in healthy humans.

BACKGROUND: High hydration is commonly used in renal studies to improve the completeness of urine collection. The renal effects of hydration are not well defined. METHODS: Renal function was studied under fasting conditions (baseline) and after a meat meal (2 g of protein/kg body weight) in 12 healthy adults on a low and high hydration regimen of 0.5 and 4 mL of oral water per kg body weight/30 min, respectively. RESULTS: Urine flow, urinary and plasma Na, K, urea, and osmolality were stably different on low and high hydration regimens. At baseline, there were significant or borderline significant correlations of plasma and urine osmolality with glomerular filtration rate (GFR; inulin clearance) only in the low hydration regimen. GFR was higher in the low than the high hydration regimen at all time points. The difference was significant at baseline (19.2%) and at 90 to 180 minutes after the meal (14.4%). After the meal, GFR increased significantly over baseline values only in the high hydration regimen (30.0% at peak time). Urinary excretion of Na, urea, and osmoles was lower in the low than the high hydration regimen at all time points: The difference was significant for Na (at baseline) and osmoles (all time points). Urinary K excretion was not different in the two regimens. After the meal, there were significant increases in urinary excretion of Na (in the low hydration regimen) and urea (90 to 180 min after the meal). CONCLUSIONS: In fasting adults, high hydration lowered GFR and increased natriuresis. After a meat meal, GFR increased only in the high hydration regimen and natriuresis only in the low hydration regimen. Hydration affects GFR and natriuresis under fasting conditions and after a meat meal.

Nephrotic edema.

This article starts with a concise synopsis of the history of edema. The role of underfilling, overflow, antidiuretic hormone, and acquaporins is subsequently discussed. Emphasis is given to the use of diuretics in edematous patients. The role and risks of albumin infusion are illustrated. The new hypothesis of pulse reverse osmosis is discussed. The final section deals with the measurement of colloid osmotic pressure in the clinical setting.

Bioelectrical impedance analysis in heart transplantation: early and late changes.

The objectives of this study were to perform bioelectrical impedance analysis before and after heart transplantation with comparison to healthy subjects. Eight patients (7 men, 1 woman) before (day 0) and after transplantation (day 3, 7, 12, 15, and 180) and 24 healthy controls, matched for sex, age, and body mass were studied. Data collection included bioelectrical impedance analysis (resistance, reactance, and estimates of body water), clinical, and laboratory measurements. Compared with controls, patients had at baseline significantly higher reactance, not significantly different resistance, body weight, total body water, and intra- to extracellular water ratio. After surgery, for reactance, there was an acute decrease followed by a slow, progressive increase up to normal level by day 15. Resistance and body weight did not significantly change; the intra- to extracellular water ratio significantly decreased with stable total body water. Changes in reactance are the main effects induced on bioelectrical impedance by heart transplantation. Acutely, there is a large decrease which likely reflects changes both in water distribution and in cell membrane function. The late changes more likely reflect the shift of body water from the extra- to the intracellular space with stable total body water.

Renal tubular function by lithium clearance in liver cirrhosis.

Increased tubule sodium reabsorption has been largely suspected in liver cirrhosis (LC), however studies in humans have produced contrasting results. Therefore to ascertain the entity of renal sodium handling in LC this study was devised. A total of 13 patients with child A LC were studied along with 26 age-sex matched healthy controls (HC). Patients and controls were kept on daily Na-intake of 100 mmol for at last 1 week, by measuring glomerular filtration rate (GFR; inulin) and lithium clearance. We have calculated (1) C(Li); (2) the absolute reabsorption of isotonic fluid in the proximal tubule (APR) as GFR - C(LI); (3) the fractional proximal sodium reabsorption (FPRNa) as 1 - (C(Li)/GFR); (4) the absolute distal reabsorption of sodium (ADRNa) as (C(LI) - C(Na)) x P(Na;) and (5) the fractional distal sodium reabsorption (FDRNa) as (C(LI) - C(Na))/C(Li). GFR was significantly lower in LC (P<.001), C(Li) was significantly higher in LC than in HC (P<.001). APRNa and FPRNa were reduced in LC (P<.0001). ADRNa was higher in LC than in HC (P<.001). No difference was found for FDRNa. In conclusion, lithium clearance discloses an increase sodium reabsorption in distal tubule in humans with LC.

Glomerular filtration rate in severely overweight normotensive humans.

The study examined whether indexing glomerular filtration rate (GFR) for body surface area is appropriate for people who are severely overweight. Twenty normotensive adult men who were severely overweight but without microalbuminuria were enrolled into this study. The control group consisted of 20 healthy subjects matched for age, sex, and height. GFR was determined by measuring insulin with the continuous-infusion method. The clearance of endogenous creatinine was also measured after two daily urine collections. Renal plasma flow (RPF) was measured by p-aminohippurate clearance using the continuous-infusion method. Lean body weight was measured by impedentiometry. Adjusting for body surface area (in 1.73 m(2)) caused a significant reduction in GFR (P < 0.0001) in overweight humans (84.1 +/- 2.32 versus 109.6 +/- 3.07 mL/min/1.73 m(2)). The difference disappeared when GFR/height criteria were adopted. No difference between obese and healthy controls occurred after adjusting for lean body weight. Data for creatinine clearance paralleled those with insulin clearance; a significant reduction (P < 0.001) occurred after indexing for basal surface area, which disappeared after correction for height, as well as for lean body weight.

Cerebral phaeohyphomycosis caused by Ramichloridium obovoideum (Ramichloridium mackenziei): case report.

OBJECTIVE AND IMPORTANCE: Only a few cerebral infections with the dark-walled mold Ramichloridium obovoideum (Ramichloridium mackenziei) have been reported in the literature. Central nervous system infections caused by this fungus have poor prognoses; the optimal medical and surgical treatments have not yet been established. We report a case of cerebral R. obovoideum infection for which a combination of medical and surgical treatments failed. CLINICAL PRESENTATION: A 58-year-old Kuwaiti woman, with a history of chronic renal failure requiring hemodialysis, presented with a 3-day history of left frontal headache, blurry vision, dizziness, and right-sided clumsiness. Computed tomography demonstrated multiple, ring-enhancing, cerebral lesions (the largest of which measured 2-3 cm) in the deep left parieto-occipital region. INTERVENTION: A computed tomography-guided needle biopsy of the parieto-occipital lesion yielded 10 ml of dark caseous fluid. Stains demonstrated long, branching, septate hyphae. Fungal cultures grew R. obovoideum. The patient was treated with a combination of amphotericin B and itraconazole. The condition of the patient continued to deteriorate, and stereotactic aspiration of the largest lesion was performed. Despite this approach, the lesion progressed and the patient died. CONCLUSION: R. obovoideum is being increasingly recognized as a cause of cerebral abscesses in patients residing in the Middle East. Prognoses are poor, and responses to antifungal therapy are generally short-lived. Until more effective therapies are found, the greatest chance for adequate treatment involves early recognition, prompt treatment with antifungal agents, and attempts at complete resection.

Bioelectrical impedance analysis before and after Novacor implantation.

In this study Bioelectrical Impedance Analysis was performed in 5 patients with end stage heart failure in whom a left ventricular assist device (Novacor) was successfully implanted. Whole body measurements of bioelectrical indices resistance and reactance were taken before surgery and 3, 7, 12, and 15 days after it. After surgery there was a significant decrease in reactance, indicating a shift of body fluids from intra- to extra-cellular space.

Effects of thyroid hormones on heart and kidney functions.

Thyroid hormones affect the functions of several organs including the heart and kidney. Using isolated left papillary muscles we have investigated the action of thyroid hormones on the mechanical and electrical properties of the heart. We found that pure hypothyroidism causes a depression in contractile and electrical parameters, but we noticed that superimposed hypoparathyroidism accounts for the marked prolongation in contractile kinetics and action potential duration. At kidney level we have shown that thyroid hormones affect proximal tubular sodium transport and this effect is only partially mediated by the action of thyroid hormones on Na-K-ATPase activity. Using the micropuncture technique, we hypothesized that the early effect of thyroid hormone action is on the potassium permeability of proximal tubular cell membrane. This latter effect would explain the increase in isotonic fluid reabsorption through an increase in the driving force for sodium. Finally, hypothyroid patients have a decrease in glomerular filtration rate and renal plasma flow that are completely reversed by thyroxine administration. On the other hand, hyperthyroid subjects exhibit a significant increase in both parameters.

Body impedance studies in end-stage heart failure.

This study adds another category of patients to those amenable to body impedance analysis (BIA). BIA measurements were obtained for the first time in 23 male patients with end-stage heart failure who were waiting for heart transplantation, and the data were compared with those obtained in 69 healthy controls matched for age, sex, height and weight. The data indicate that in end-stage heart failure there is an increased reactance (p<0.01) and an altered intracellular water/extracellular water ratio (p<0.03) due to the increased intracellular water (p<0.01) and decreased extracellular water (p<0.01).

Renal reserve is normal in patients with dilative cardiomyopathy waiting for heart transplantation.

Renal reserve was explored by means of an oral protein load (2 g/kg body weight) under the form of cooked red meat in a group of 9 patients with end-stage heart failure (ESHF), class III of the New York Heart Association receiving loop diuretics and angiotensin-converting enzyme (ACE) inhibitors, and in a group of 18 healthy controls (HC) matched for age, gender, and height under an identical dietary regimen providing 40 cal/kg per day, 1 g/kg body weight of protein per day, Na 120 mmol/day, and K 50 mmol/day. Baseline glomerular filtration rate averaged 109.5+/-9.89 ml/min x 1.73 m2 in HC and 71.9+/-8.8 ml/min x 1.73 m2 in ESHF. Renal plasma flow averaged 540+/-27 ml/min x 1.73 m2 in HC and 235+/-47 ml/min x 1.73 m2 in ESHF. The filtration fraction was significantly higher in ESHF (p<0.01). Renal reserve averaged 26.03+/-3.28 ml/min x 1.73 m2 in HC and 27.2+/-7.12 ml/min x 1.73 m2 (not significant). Renal reserve averaged 123.9+/-2.9% in HC and 137.3+/-6.68% in ESHF (not significant). The filtration capacity was significantly higher in HC (p<0.001). The data point to a normalcy of renal reserve in ESHF which may depend on the chronic use of ACE inhibitors.

Measurement of glomerular filtration rate by the 99mTc-DTPA renogram is less precise than measured and predicted creatinine clearance.

The work was devised to compare measurements of glomerular filtration rate (GFR) by technetium-99m-diethylenetriaminepentacetic acid (99mTc-DTPA) renogram to those by creatinine clearance (measured and predicted by Cockroft and Gault) and by inulin clearance. A total number of 65 individuals were enrolled: 15 healthy controls and 50 patients with renal disease. Compared to inulin clearance used as the gold standard, 99mTc-DTPA overestimated at low and underestimated at high GFRs. 99mTc-DTPA measurements were less precise than creatinine clearance except for individuals with GFR >100 ml/min x 1.73 m2. Measured creatinine clearance had the highest correlation coefficient with inulin clearance, 99mTc-DTPA clearance the lowest. In correlation analyses, 81.5% of the interindividual variability for measured creatinine clearance could be explained by true differences in inulin clearance; this value dropped to 59.1 and 57.4% for predicted creatinine clearance and 99mTc-DTPA, respectively. In patients with GFR <25 ml/min x 1.73 m2, all 99mTc-DTPA measurements were out of the 95% confidence interval for the inulin measurement. It can be inferred that 99mTc-DTPA clearance from the renogram is less precise than measured and predicted creatinine clearance.

Effects of a meat meal on renal sodium handling and sodium balance.

Protein ingestion increases renal blood flow and glomerular filtration rate (GFR). This study investigated in healthy adults if the renal response to protein ingestion includes changes in urinary sodium (Na) excretion rate and Na balance. Renal clearance of Na and inulin (used as index of GFR) were measured in 25 healthy adults before (90 min) and after (180 min) a standard meal and, as control, before and after administration of water and Na-chloride (saline). The meal consisted of red lean meat (2 g protein/kg body weight); in control experiments, water and Na were given to match water and Na content of the meal. ANOVA for repeated measures, Student's t-test, and linear regression were used for statistical analysis. GFR and urinary Na excretion increased over baseline after the meal (p < 0.001), not after saline. The post-meal natriuretic response was accounted for an early (0-90 min) increase in glomerular filtered load of Na (p < 0.001) and a late (90-180 min) reduction in tubular Na reabsorption (p < 0.02). Urine flow rate and plasma Na did not significantly change after the meal and in control experiments. Analysis of Na balance showed that post-meal Na excretion was significantly higher than baseline also after Na balance returned to pre-meal values. In healthy individuals, a meat meal stimulates natriuresis and causes a net decrease in Na balance. The renal natriuretic response to the meal appears secondary to the meal-induced changes in renal hemodynamics. The data are in keeping with the hypothesis that dietary protein intake affects also renal Na handling.