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Biomedical subjects

S P Andreoli

Publications and source records attributed to S P Andreoli.

At least 19 recordsLinked to original sources
PubMed2001

Validation of PD Adequest 2.0 for pediatric dialysis patients.

Kinetic modeling has proven to be a valuable tool for peritoneal dialysis (PD) prescription in adult PD patients. The clinical application of this procedure has rarely been studied in children. We therefore evaluated the PD Adequest 2.0 for Windows program (Baxter Healthcare Co., Deerfield, IL) as a prescription aid for the management of pediatric PD patients by comparing the measured and predicted PD clearances, total drain volumes, and net ultrafiltration in 34 children (15 males) (mean age 10.9 +/- 6.0 years) receiving long-term PD. In each case, a 4-h peritoneal equilibration test was conducted with a standardized test exchange volume of 1,100 ml/m2 BSA. A total of 43 24-h dialysate (plus urine in 12) collections were analyzed. The levels of agreement between measured and predicted values for weekly peritoneal and total urea Kt/V, weekly peritoneal and total creatinine clearance, daily drain volume, net ultrafiltration and daily peritoneal urea and creatinine mass removal were assessed with correlation coefficients (re) and Bland-Altman limits of agreement. The study revealed that there is a basic level of agreement between measured and modeled values for solute removal and total drain volume, with correlation coefficients ranging from 0.75 to 0.98. In contrast, the rc for net ultrafiltration was only 0.34. The majority (75%) of patients had modeled urea and creatinine clearances that were within 20% of their measured values. These data suggest that the PD Adequest 2.0 for Windows program can predict urea and creatinine clearances with reasonable accuracy in pediatric PD patients, making it a valuable resource in prescription management.

Child↗
PubMed2000

History of the National Kidney Foundation's research efforts.

The research programs of the National Kidney Foundation (NKF) are designed to foster research and training in renal disease by providing cutting edge, excellent, state of the art training in basic science, clinical, and translational research. Since the inception of the Fellowship training program in 1968, the beginning of the Young Investigator Grant program in 1987, and the establishment of the Clinical Scientist Award in 1994, hundreds of nephrologists and basic scientists have been supported by the NKF research programs. The annual budget for the various research and training programs of the NKF has increased from approximately $80,000 to more than $1,000,000 for the Fellowship training program, from about $90,000 to more than $400,000 for the Young Investigator Grant program, and from $50,000 to $500,000 annually for the Clinical Scientist award for a total of more than $2,000,000 annually, while future plans are to expand the research budget to almost $3,000,000 annually. In addition to these programs to support outstanding research and training from the national office, many Affiliate chapters of the NKF also support research and training as a mission. It is the goal of the NKF that the research supported by the NKF will ultimately be translated into improved quality of care for patients with kidney disease. Because progress in many diseases is hampered by a lack of knowledge of the underlying pathophysiology of the disease, improved understanding of the mechanisms of renal disease will allow for the development of strategies to prevent or limit renal disease. The NKF is committed to continuing its focus on research and training as one of its major missions so that patients with kidney disease can live better lives in the next millennium.

Awards and Prizes↗
PubMed1999

Adverse effect of peritonitis on peritoneal membrane function in children on dialysis.

The effect of peritonitis on peritoneal membrane solute transport characteristics was determined as part of a multicenter study in children on continuous ambulatory/cycling peritoneal dialysis. Ninety-three children each underwent a 4-h peritoneal equilibration test (PET) with 1,100 ml/m2 2.5% Dianeal for determination of mass transfer area coefficients (MTAC), dialysate to plasma ratios (D/P) for creatinine and urea at 0, 30, 60, 120, 180, and 240 min and dialysate glucose levels at 0, 30, 60, 120, 180, and 240 min for calculation of D/Do. The mean age of the study cohort was 10.1 +/- 5.6 years (range 0.1-19 years). There were 162 historical episodes of peritonitis; at the time of the PET tests, 36 children had never had an episode of peritonitis (group I) while 57 children had a history of one or more episodes of peritonitis (group II). In group II children, the 4-h glucose D/Do was significantly lower and the 4-h D/P creatinine ratio, the creatinine MTAC, and the glucose MTAC were significantly higher (each P < 0.05) than in group I. In children with a history of peritonitis caused by Gram-negative organisms, the 4-h glucose D/Do (P < 0.05) and the creatinine MTAC (P < 0.05) were significantly lower and the glucose MTAC (P = 0.07) nearly significantly lower than in children without a history of peritonitis. Linear regression analysis did not demonstrate a correlation between any of the variables and duration of peritoneal dialysis, while the rate of peritonitis was weakly correlated with glucose MTAC (r = 0.34, P < 0.05) and with 4-h glucose D/Do (r = -0.222, P < 0.01). We conclude that children with a history of peritonitis have peritoneal membranes that are more permeable to glucose and creatinine than children without a history of peritonitis, and that the peritoneal membranes of children who have had peritonitis caused by Gram-negative organisms are also more permeable to creatinine and glucose. Such changes are likely to have an adverse effect on membrane function and could eventually contribute to ultrafiltration failure.

Adolescent↗
PubMed1999

Longitudinal evaluation of transport kinetics in children receiving peritoneal dialysis.

Functional stability of the peritoneal membrane is necessary for maintenance of peritoneal dialysis (PD) as a therapeutic option. Few studies have investigated this issue in children. We evaluated the peritoneal membrane solute transport capacity longitudinally in 26 children (mean age 11.0+/-5.5 years) receiving long-term PD. Each patient underwent a standardized peritoneal equilibration test on two occasions (mean interval between studies 19.8+/-5.9 months) to determine solute dialysate to plasma (D/P) ratios, dialysate glucose to initial dialysate glucose (D/D(0)) ratios, and mass transfer area coefficients (MTAC). The correlation of transport capacity with peritonitis history was also assessed. No significant change in MTAC, D/P, or D/D(0) values were found when comparing original and follow-up data of the group overall. However, transport of creatinine and glucose was significantly (P<0.05) greater in the peritonitis group compared with the group without peritonitis, and differences in the change over time between the peritonitis groups was significant for MTAC creatinine (P=0.035) and D/D(0) glucose (P=0.020). In summary, this experience demonstrates functional stability of the peritoneal membrane in pediatric patients receiving PD. However, follow-up assessments of peritoneal solute kinetics may be necessary in patients with a history of peritonitis in order to permit early identification of those who may be at risk for ultrafiltration failure and sclerosing peritonitis.

Adolescent↗
PubMed1999

Effect of macroscopic air bubbles on cell lysis by shock wave lithotripsy in vitro.

In studies of cells or stones in vitro, the material to be exposed to shock waves (SWs) is commonly contained in plastic vials. It is difficult to remove all air bubbles from such vials. Because SWs reflect at an air-fluid interface, and because existing gas bubbles can serve as nuclei for cavitation events, we sought to determine in our system whether the inclusion of small, visible bubbles in the specimen vial has an effect on SW-induced cell lysis. We found that even small bubbles led to increased lysis of red blood cells (1- to 3-mm diameter bubbles, 9.8+/-0.5% lysis, n = 7; no bubbles, 4.4+/-0.8%, n = 4), and that the degree of lysis increased with bubble size. Damage could not be reduced by centrifuging the cells to the opposite end of the vial, away from the bubble. B-scan ultrasound imaging of blood in polypropylene pipette bulbs showed that, with each SW, bubbles were recruited from the air interface, mixing throughout the fluid volume, and these appeared to serve as nuclei for increased echogenicity during impact by subsequent SWs; thus, bubble effects in vials could involve the proliferation of cavitation nuclei from existing bubbles. Whereas injury to red blood cells was greatly increased by the presence of bubbles in vials, lytic injury to cultured epithelial cells (LLC-PK1, which have a more complex cytoarchitecture than red blood cells) was not increased by the presence of small air bubbles. This suggests different susceptibility to SW damage for different types of cells. Thus, the presence of even a small air bubble can increase SW-induced cell damage, perhaps by increasing the number of cavitation nuclei throughout the vial, but this effect is variable with cell type.

Epithelial Cells↗
PubMed1999

The pathophysiology of the hemolytic uremic syndrome.

The hemolytic uremic syndrome is an important cause of acute renal failure and leads to substantial morbidity and mortality. In pediatric patients, the hemolytic uremic syndrome usually follows hemorrhagic colitis caused by verocytotoxin-producing Escherichia coli. Several well-publicized outbreaks of hemorrhagic colitis and hemolytic uremic syndrome have highlighted the morbidity and mortality of infection with verocytotoxin-producing Escherichia coli. Recent studies have further demonstrated the role of verocytotoxins in mediating renal cell injury and the mechanisms of verocytotoxin cell injury. Although the endothelial cell appears to be the major target of verocytotoxin-mediated cell injury, studies have also shown that mesangial cells, renal tubular epithelial cells, monocytes and cells derived from the monocytic cell line are also targets of verocytotoxin-mediated biological effects. It has also been shown that inflammatory cytokines are likely to play an important role in hemolytic uremic syndrome. Serum levels of IL-8 and TNF-alpha are elevated in hemolytic uremic syndrome and verocytotoxins promote the generation of inflammatory cytokines from monocytes and monocyte-derived cell lines. These new findings have important implications for current therapy and potential future therapy of hemolytic uremic syndrome.

Animals↗
PubMed1998

Response of crescentic Henoch-Schoenlein purpura nephritis to corticosteroid and azathioprine therapy.

The benefits of treating severe Henoch-Schoenlein Purpura (HSP) glomerulonephritis have not been established. In this study, we evaluate the outcome of 21 children with severe HSP nephritis treated with corticosteroids and azathioprine. Between 1977 and 1995, 78 children (age range 1 to 16 years) were seen for evaluation of HSP. Thirty-one underwent kidney biopsy; indications included nephritic and/or nephrotic onset (15 patients), persistently decreased creatinine clearance (5 patients), or proteinuria > 4 g/24 h (11 patients). Twenty treated patients had diffuse mesangial proliferation with crescents in 6-100% (mean 40%) of glomeruli. One treated patient, not biopsied due to extreme obesity, had a creatinine clearance of 49 ml/min/1.73 m2 and proteinuria of 21.3 g/24 h. These 21 patients were initially treated with azathioprine and daily oral prednisone (13 patients) or i.v. methyl-prednisolone (8 patients), followed by azathioprine and alternate-day prednisone for 9-24 (mean 15) months. The average follow-up was 32 months. Over the course of follow-up, 19 treated patients showed a decline in hematuria (> 5 red blood cells/high power field) from 100% to 16% (p < 0.01), a fall in the serum creatinine from 1.71 +/- 2.20 to 0.78 +/- 0.25 mg/dl (p < 0.01), an increase in creatinine clearance from 76 +/- 43 to 122 +/- 26 ml/min/1.73 m2 (p < 0.01), and a reduction in proteinuria from 8.8 +/- 7.5 to 0.47 +/- 0.39 g/24 h (p < 0.01). Two treated patients progressed to end-stage renal failure. There was no difference in outcome comparing patients initially treated with prednisone versus methyl-prednisolone. These observations suggest that corticosteroid and azathioprine therapy is effective in crescentic HSP nephritis.

Adolescent↗
PubMed1998

Livedo reticularis, developmental delay and stroke-like episode in a 7-year-old male.

Livedo reticularis is a vascular abnormality of the skin resulting in an erythematous reticular rash. The combination of livedo reticularis and stroke-like episodes in adults is known as Sneddon syndrome [Sneddon, IB (1965). Br J Dermatol 77:180-188]. A similar combination of stroke-like episodes and livedo reticularis has been reported to occur in children [Baxter P et al. (1993). Dev Med Child Neuro 35:917-926]. We present here a 7-year-old male with congenital livedo reticularis, obesity, developmental delay, stroke-like episode, hypertension and cystic kidneys. We summarize our patient's findings and family history, and compare his disorder to other possibly related conditions.

Adult↗
PubMed1998

Renal manifestations of systemic diseases.

During childhood, the kidney may be involved in several different systemic diseases including the vasculitic syndromes, collagen vascular diseases, and the thrombotic microangiopathic diseases. This article discusses three of the more common systemic disease including Henoch Schonlein Purpura (HSP), systemic lupus erythematosus (SLE), and the hemolytic uremic syndrome (HUS), which occur during childhood. Each of these diseases have important renal manifestations that may present with hematuria with or without proteinuria, hypertension, rapidly progressive glomerulonephritis, and/or with acute renal failure. The occurrence of these diseases during childhood raises lifelong concerns for the child's renal function. As in glomerulonephritis associated with SLE, reactivation of the underlying disease can result in additional renal injury, whereas late extrarenal and renal complications may be observed following HUS or nephritis associated with HSP. These diseases are not only an important cause of acquired chronic renal failure during childhood, but may also lead to end-stage renal disease or other complications that do not become apparent until adulthood. In each disease, we will review the clinical manifestations, the pathology, pathophysiology, and current management and therapy.

Child↗
PubMed1997

The effect of polypropylene vials on lithotripter shock waves.

In studies to understand the mechanisms responsible for shock wave lithotripsy (SWL) cell injury, we observed that shock waves (SWs) are influenced by the shape of the specimen vial. Lytic injury to kidney cells treated in a Dornier HM3 lithotripter was higher (p < 0.0001) when SWs entered the vial through the flat end (cap end) compared to the round end. Measurements of the acoustic field within polypropylene vials were carried out using both lithotripter SWs and pulsed ultrasound (US) in the megahertz frequency range. We compared pressure amplitudes inside the round and flat vials and found significant differences. When SWs entered through the round end, the average peak positive pressure was 40% of free-field pressure, due mostly to a dramatic reduction in pressure off axis. The average peak pressure inside the flat vial was twice that of the round vial. Experiments with US demonstrated that sound field focusing was induced by the curved interface of the round vial. Ray analysis for the round vial indicates the presence of "hot spots" on axis and "cold spots" off axis, in qualitative agreement with pressure profiles. We conclude that the shape of the specimen vial is an important factor that should be considered in model systems of SWL cell injury.

Animals↗
PubMed1997

Disassociation of oxidant-induced ATP depletion and DNA damage from early cytotoxicity in LLC-PK1 cells.

To determine the mechanism(s) of oxidant-mediated cell lysis in renal tubular epithelial cells, we determined ATP depletion, DNA damage, lipid peroxidation, and cytotoxicity in LLC-PK1 cells exposed to 500 microM hydrogen peroxide for 1 h with and without inhibitors of lipid peroxidation including a lazaroid compound, 2-methylaminochroman (2-MAC), and Trolox, a vitamin E analog. ATP levels were determined by luciferin-luciferase, DNA damage by the alkaline unwinding technique, lipid peroxidation by the generation of malondialdehyde, and early cytotoxicity (5 h) by the release of 51Cr, whereas late cytotoxicity (24 h) was determined by release of [3H]leucine from prelabeled cells. Cells exposed to 500 microM hydrogen peroxide demonstrated significant (P < 0.01) ATP depletion, DNA damage, and lipid peroxidation, followed by cell death at 5 h. Concentrations of 0.1-25 microM 2-MAC or 25-500 microM Trolox each markedly and significantly (P < 0.01) inhibited lipid peroxidation and early cytotoxicity but had little to no effect on ATP depletion or DNA damage. Thus oxidant-stressed cells remained intact for several hours despite significant ATP depletion and DNA damage when lipid peroxidation was inhibited with the antioxidant compounds. At 24 h, 2-MAG and Trolox had lost their protective effect, suggesting that mechanisms other than lipid peroxidation play a role in later cytotoxicity. We conclude that ATP depletion and DNA damage are not the primary mediators of early cytotoxicity following oxidant stress, whereas lipid peroxidation plays an central role in mediating early cytotoxicity following oxidant injury.

Adenosine Triphosphate↗
PubMed1995

Response of type I membranoproliferative glomerulonephritis to pulse methylprednisolone and alternate-day prednisone therapy.

Sixteen children with biopsy-confirmed type I membranoproliferative glomerulonephritis (MPGN) were treated with six alternate-day intravenous pulses of methylprednisolone followed by single-dose alternate-day prednisone for 12-66 months (mean 37 months). The average length of follow-up was 52 months (range 12-127 months). Compared with pretreatment values, the frequency of hematuria (13/16 vs. 8/16, P < 0.05) and the levels of serum albumin (2.66 +/- 0.69 vs. 3.76 +/- 0.39 g/dl, P < 0.001), creatinine clearance (97 +/- 37 vs. 129 +/- 26 ml/min/1.73 m2, P < 0.001), and proteinuria (5.2 +/- 5.1 vs. 1.0 +/- 0.8 g/day, P < 0.001) were significantly improved after 3 months of therapy. Improvement has persisted through the end of the follow-up period. Repeat kidney biopsies showed a significant reduction in acute changes but an increase in chronic changes. Thirteen patients have been off therapy from 1 to 74 months (mean 20.8 months). Nine have a normal urinalysis, creatinine clearance, and protein excretion. The remainder have normal renal function but proteinuria ranging from 3.2 to 4.3 g/day. The data support the evidence of other investigators that corticosteroid therapy is beneficial in type I MPGN and suggest that initiation with pulse methylprednisolone may promote early stabilization of the disease.

Adolescent↗