Riccardo Lubrano

Red Blood Cell Membrane Lipid Peroxidation in Continuous Ambulatory Peritoneal Dialysis Patients

We have recently described that in the erythrocytes from uremic patients on chronic hemodialysis, the pentose-phosphate shunt is defective, the membrane concentrations of malonyldialdehyde, resulting from peroxidation of polyunsaturated fatty acids in the membranes themselves, are increased, and the concentrations of vitamin E, an antioxidizing agent, are reduced. In the present study we have analyzed these same metabolic aspects in a group of uremic patients in continuous ambulatory peritoneal dialysis. We have found normal function of the pentose-phosphate shunt, slightly elevated concentrations of malonyldialdehyde compared to controls, but definitely lower than in chronic hemodialysis patients, and higher tocopherol concentrations than in both controls and chronic hemodialysis patients.

Relationship between global end-diastolic volume and cardiac output in critically ill infants and children

Objective:The objective of this study was to investigate possible correlations between the preload index global end-diastolic volume (GEDV) and the indexes of cardiac function, cardiac index, and stroke volume index in critically ill pediatric patients. The aim was to evaluate whether GEDV may help in the decision-making process concerning volume loading. Design:Prospective clinical study. Setting:Pediatric intensive care unit of the Bambino Gesù Children’s Research Hospital. Patients:Seventy patients, 40 male and 30 female, mean age 62 ± 41 months (range 5–156 months), divided into six groups: group A, hemorrhagic shock, ten cases; group B, head injury, 21 cases; group C, septic shock, ten cases; group D, encephalitis, ten cases; group E, respiratory failure, nine cases; group F, cardiogenic shock, ten cases. Interventions:All patients received volumetric hemodynamic monitoring following initial resuscitation and every 4 hrs thereafter or whenever a hemodynamic deterioration was suspected. During the cumulative in-hospital stay, a total 1,184 sets of measurements were done. Measurements and Main Results:Findings are consistent with a statistically significant linear correlation of GEDV with cardiac index and stroke volume index in hemorrhagic shock (group A) (R2 = .647, p < .0001; R2 = .738, p < .0001) and cardiogenic shock (group F) (R2 = .645, p < .0001; R2 = .841, p < .0001). Conclusions:GEDV may potentially be a useful guide to treatment in preload-dependent conditions, such as hemorrhagic and cardiogenic shock. In the other groups where there is little relationship between preload and cardiac function indexes, the influence of non-preload-dependent mechanisms on cardiac output is certainly more significant.

Bilateral mandibular cysts associated with cyclosporine use: A case report

Abstract. Cyclosporin A (CsA) is used in the treatment of patients undergoing renal transplantation. There are a number of side effects associated with its use. In particular, the gingival overgrowth represents the most important in the oral cavity. The authors present a case of bilateral mandibular cysts in an 8-year-old boy, treated with CsA after renal transplantation. The genesis of the mandibular cysts might be associated with the combined use of CsA and a calcium channel blocker post-transplantation. CsA-induced gingival overgrowth might contribute to cysts by two mechanisms: interference with control mechanisms that regulate the reabsorption of gingival stromal tissue, allowing progressive dental eruption, and an increase in the gingival connective tissue components. Gingival hypertrophy might mechanically obstruct the eruption of the developing tooth.

Epilepsy and innate immune system: A possible immunogenic predisposition and related therapeutic implications

Recent experimental studies and pathological analyses of patient brain tissue samples with refractory epilepsy suggest that inflammatory processes and neuroinflammation plays a key-role in the etiopathology of epilepsy and convulsive disorders. These inflammatory processes lead to the secretion of pro-inflammatory cytokines responsible for blood-brain-barrier disruption and involvement of resident immune cells in the inflammation pathway, occurring within the Central Nervous System (CNS). These elements are produced through activation of Toll-Like Receptors (TLRs) by exogenous and endogenous ligands thereby increasing expression of cytokines and co-stimulatory molecules through the activation of TLRs 2, 3, 4, and 9 as reported in murine studies.It has been demonstrated that IL-1β intracellular signaling and cascade is able to alter the neuronal excitability without cell loss. The activation of the IL-1β/ IL-1β R axis is strictly linked to the secretion of the intracellular protein MyD88, which interacts with other cell surface receptors, such as TLR4 during pathogenic recognition. Furthermore, TLR-signaling pathways are able to recognize molecules released from damaged tissues, such as damage-associated molecular patterns/proteins (DAMPs). Among these molecules, High-mobility group box-1 (HMGB1) is a component of chromatin that is passively released from necrotic cells and actively released by cells that are subject to profound stress. Moreover, recent studies have described models of epilepsy induced by the administration of bicuculline and kainic acid that highlight the nature of HMGB1-TLR4 interactions, their intracellular signaling pathway as well as their role in ictiogenesis and epileptic recurrence.The aim of our review is to focus on different branches of innate immunity and their role in epilepsy, emphasizing the role of immune related molecules in epileptogenesis and highlighting the research implications for novel therapeutic strategies.

Successful management with interferon Alpha-2a after prednisone therapy failure in an infant with a giant cavernous hemangioma

A giant cavernous hemangioma of the left arm with severe thrombocytopenia and consumptive coagulopathy was observed in a neonate. Initial treatment with prednisone, platelet transfusions, and clotting replacement failed to control the bleedings. The child was then treated with daily subcutaneous infusions of interferon alpha-2a. Coagulopathy rapidly improved and transfusions were drastically reduced. The hemangioma regressed progressively and disappeared after 4 months of treatment.

Lack of Oxidative Damage in Serum Polyunsaturated Fatty Acids before and after Dialysis in Chronic Uremic Patients

We described previously that in the erythrocytes and mononuclear blood cells from uremic patients on chronic hemodialysis, the membrane concentrations of malonyldialdehyde (MDA), resulting from peroxidation of polyunsaturated fatty acids (PUFA) in the membrane itself increased, and the concentrations of vitamin E (VIT E), the major antioxidizing agent, were lower. In the present study we analysed whether similar oxidative damage is seen in the serum from hemodialysis patients and whether the serum fatty acid pattern is affected. No evidence was found of oxidative damage in the serum during hemodialysis, serum concentrations of MDA and VIT E remaining constant before and after dialysis. No change was observed in serum pattern of PUFA, particularly linoleic acid. We therefore assume that the oxidative damage described in uremic patients is mainly intracellular.

Influence of physical activity on cardiorespiratory fitness in children after renal transplantation

BACKGROUND Cardiorespiratory fitness is significantly reduced in children with end-stage renal disease. The role of renal transplantation in improving cardiorespiratory fitness has not been thoroughly investigated. METHODS In this work, we wanted to assess whether, in children after a successful renal transplant, the amount of weekly physical exercise affects cardiorespiratory fitness and left ventricular mass (LVM). The study was conducted on 16 children after renal transplantation and 36 matching healthy controls. Four groups were formed according to the weekly amount of physical exercise; all children received an echocardiogram and underwent a treadmill exercise test according to the Bruce protocol. RESULTS Cardiorespiratory fitness is worst in renal transplant children with a weekly physical exercise<3 h; renal transplant children with a physical exercise of 3-5 h per week attain a cardiorespiratory fitness comparable to controls with a sedentary lifestyle (<3-h exercise per week); healthy controls with a weekly physical exercise of 3-5 h per week show the highest levels of cardiorespiratory fitness; the LVM assessed via echocardiography follows the same pattern. CONCLUSIONS In children with a successful renal transplant, a weekly physical exercise of 3-5 h significantly improves the cardiorespiratory fitness and the LVM, up to the level of matching healthy controls with a sedentary lifestyle (<3 h exercise per week).

Erythrocyte membrane lipid peroxidation before and after vitamin E supplementation in children with cholestasis

In 10 children with chronic cholestasis and without neurologic signs, we evaluated lipid peroxidation and vitamin E levels in serum and in the erythrocytes before and after a therapeutic trial with alpha-tocopherol. We also studied the effects of vitamin E administration on hematocrit and hemoglobin values and on reticulocyte and erythrocyte counts. Plasma and erythrocyte malonyldialdehyde (MDA) values were significantly higher compared with normal control values, whereas plasma and erythrocyte tocopherol measurements were lower. Oral administration of high doses of vitamin E (300 mg/day for 15 days) resulted in lower serum MDA levels, whereas serum vitamin levels did not change significantly. In erythrocytes, the MDA decreased but not to control levels, and vitamin E increased but to lower values than normal. Hematologic values also improved. We conclude that longer treatment might be necessary to completely reverse the oxidative damage associated with vitamin E deficiency in children with cholestasis.

Noninvasive ventilation for acute respiratory distress in children with central nervous system disorders

BACKGROUND Acute respiratory distress (ARD) is a relatively frequent occurrence in patients suffering from central nervous system disorders (CNSD) and moderate to severe mental retardation. Whenever conventional therapy is little effective, noninvasive mechanical ventilation (NIV) is the additional treatment in patients with diseases of the peripheral nervous system. However, NIV is traditionally little employed in the acute phase in patients suffering from CNSD. In the latter, either conventional therapy is maintained or invasive mechanical ventilation is instituted if the patients condition worsens severely. To challenge the traditional view, we conducted the study to prove that NIV is both applicable and effective in the treatment of ARD also in children with moderate to severe mental retardation. METHODS We studied 44 children with ARD secondary to pneumonia and CNSD causing moderate to severe mental retardation. The children were divided in two groups. One group received conventional therapy and NIV, the other conventional therapy only, before being advanced to invasive ventilator support when nonresponding. On admission to hospital and one hour following admission we registered pH, PaCO(2), PaO2, A - a DO2 and the PaO2/FiO2 ratio. The mean hospital stay was also recorded. RESULTS After one hour on NIV PaO2 and pH increased, PaCO(2) decreased, A - a DO2 and PaO2/FiO2 ratio improved. No changes in the above parameters were observed in children on conventional therapy only. Hospital stay was shorter when NIV was instituted. CONCLUSIONS NIV is both applicable and beneficial in stabilizing blood gases, respiratory and cardiovascular parameters also in children with CNSD. Moreover its use shortens the hospital stay.

Pregnancy in a Methylmalonic Acidemia Patient With Kidney Transplantation: A Case Report

Presently pregnancy is no more exceptional in women with metabolic diseases. However, it still poses significant medical problems both before and after childbirth. The challenge is even greater if the mother has undergone organ transplantation, because of her metabolic disease. We report on a case of pregnancy in a patient 29‐year‐old with methylmalonic acidemia cblA type (OMIM 251100) who received a renal transplantation at the age of 17 for end‐stage renal disease (ESRD) caused by her primary disease. During pregnancy neither metabolic crises nor renal function changes were observed in the mother, with the only exception of a mild increase of her systemic blood pressure. To the fetus pregnancy was uneventful and during the first 30 months after birth the babys neuropsychomotor development was normal and there were no episodes of metabolic derangement. This is evidence that methylmalonicacidemia cblA, even when treated with renal transplantation for inherent ESRD, is no contraindication to pregnancy. It is even possible that a functioning transplanted kidney contributes to improve metabolic parameters.