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Biomedical subjects

Dominique C Belli

Publications and source records attributed to Dominique C Belli.

7 recordsLinked to original sources

Glomerular and tubular function following orthotopic liver transplantation in children.

UNLABELLED: Since its advent, cyclosporine nephrotoxicity has been a major concern to pediatricians attending to liver transplant recipients. The aims of this study were to examine glomerular and tubular function after orthotopic liver transplantation (OLT) in children, their correlation to CsA, and how they differed according to the underlying disease. PATIENTS AND METHODS: Glomerular and tubular function was examined in 28 patients aged 7 months to 14 yr at the time of transplantation (mean 4.0 +/- 3.6), retrospectively examining creatinine clearance, tubular phosphate reabsorption (TRP), calcium/creatinine ratio, sodium excretion fraction, and protein/creatinine ratio. The group with metabolic disease and an underlying tubulopathy was compared with the group with liver disease only. The effect of CsA trough levels and cumulated dose on these indices was examined, as was the effect of antihypertensives on creatinine clearance. Both glomerular and tubular functions improved significantly following liver transplantation. In patients on CsA (n = 21), CrCl decreased significantly at 1 month post-OLT (42.6 +/- 26.6 mL/min/1.73 m(2)) when compared with pretransplantation, and 3, 12 and 60 months post-OLT (p < 0.05). It improved between 12 and 60 months post-OLT (p < 0.05). It was correlated with cyclosporine trough levels (p < 0.03), and with total dose of CsA at 12 months. This was not true for patients on tacrolimus (n = 7). Overall pretransplant TRP was below normal (73.7% +/- 19.6), which was significantly lower than the values at years 2, 3, and 5 post-OLT (p < 0.05), owing mainly to the metabolic group which recovered normal proximal tubular function by the end of the second week post-OLT. Calcium/creatinine ratio was significantly worse in the group with liver disease only (p < 0.01). Protein/creatinine ratio normalized rapidly in both groups. Urinary sodium excretion fraction (FENa) was very abnormal in the early postoperative phase, normalizing thereafter in both groups. Kidney function improved after liver transplantation in patients with and without pre-existing kidney dysfunction. Overall, creatinine clearance was correlated to CsA trough levels suggesting CsA did not have an irreversible 'sclerosing' effect in the medium term. Combined antihypertensive therapy using nifedipine and enalapril may be the optimal choice for patients requiring medical management of their hypertension, although the observed effect on creatinine clearance did not reach statistical significance in this study. Tubular dysfunction is frequent in both groups of patients, pre- and post-transplant, and may contribute to bone mineral density as well as to metabolic disturbances in this population.

Adolescent↗

24-hour electrocardiogram before and during cisapride treatment in neonates and infants.

We studied prospectively the effects of cisapride on heart rate and rhythm using standard ECG and 24-hour ECG recordings in term and preterm neonates and infants. We studied subjects with gastroesophageal reflux disease (apparent life-threatening events, apneas, bradycardias) before and 3 days after starting cisapride (0.8 mg/kg/day in 4 doses). We performed standard ECGs for determination of corrected Q-T interval (QTc) and Q-T dispersion (QTd) and 24-hour ECG recordings for analysis of heart rate, heart rate variability, and heart rhythm. Fourteen term and 17 preterm subjects (gestational age range 28-36 weeks) were studied at a median chronological age of 29 (range 3-132) days. Cisapride significantly increased the QTc in preterm infants (before vs. after: 408 +/- 7 vs. 433 +/- 7 ms, p = 0.001). Two preterm and 1 term infant had a QTc >450 ms before cisapride. Four preterm (4/15 = 27%) and 2 term (2/13 = 15%) subjects had a QTc >450 ms on cisapride. After cisapride the QTd remained normal, and no relevant arrhythmias were documented on Holter recordings. Cisapride significantly decreased peak and mean heart rates of all study subjects without affecting the heart rate variability, while it increased the minimal heart rate of preterm infants only (before vs. after: 66 +/- 5 vs. 78 +/- 5 bpm, p = 0.02). The maximally measured R-R intervals (pauses) decreased after cisapride in preterm infants (before vs. after: 1.33 +/- 0.2 s vs. 1.05 +/- 0.2 s, p = 0.04). Although cisapride did cause a significant prolongation of the ventricular action potential duration in preterm infants, the QTd remained unaffected, and no clinically relevant arrhythmias were documented in this small sample. On the other hand, cisapride had a direct lowering effect on the maximal and mean heart rates of both term and preterm infants, while the drug increased the minimal heart rate and reduced the severity of bradycardia episodes in preterm infants.

Arrhythmias, Cardiac↗

Electrogastrography reveals post-prandial gastric dysmotility in children with cystic fibrosis.

OBJECTIVES: Cystic fibrosis patients have a wide spectrum of gastrointestinal disorders. The aim of this study was to investigate the function of gastroenteric neuromusculature and its response to a prokinetic. METHODS: 14 CF children aged 8.6 + 1.3 years were studied by electrogastrography and compared to 10 age-matched controls. A second recording was performed in CF patients after administration of cisapride (0.3 mg/kg). Parameters analyzed were percentage of normal gastric rhythm (2.0 to 4.0 cpm), percentage of tachygastria (4.0 to 9.0 cpm), dominant frequency instability coefficient and power ratio. RESULTS: CF and control groups were not different in age, height or weight. A significant post-prandial increase in percentage of tachygastria (26.7 + 4.5 versus 12.4 + 2.6; P < 0.05) was seen in CF patients, which was not corrected by cisapride. The power ratio showed a statistical increase in 3 cpm (3.7 + 0.8 versus 1.6 + 0.3; P < 0.05) and in tachygastria (5.3 + 1.2 versus 1.7 + 0.4; P < 0.03) in CF compared with controls. Cisapride had an effect on tachygastria power ratio (3.0 + 0.5; P < 0.04). Analysis of normal rhythm and the dominant frequency instability coefficient were not statistically different in CF and controls. CONCLUSION: This study provides evidence of gastric dysmotility in CF patients.

Adolescent↗

Homocysteine prevents total parenteral nutrition (TPN)-induced cholestasis without changes in hepatic oxidative stress in the rat.

BACKGROUND: The role of oxidative stress in total parenteral nutrition (TPN)-associated cholestasis with liver glutathione depletion was recently shown. The aims of this study were to test the appearance of cholestasis and oxidative stress during TPN, and the hypothesis that reducing oxidative stress with a precursor of glutathione (GSH), homocysteine, would restore bile flow. METHODS: Three groups of rats (weight, 179-278 g) were studied: 1) D/aa group received dextrose and amino acids (3.4 g/d); 2) D/aa/L group received the same amount of amino acids, and lipids were added on an equicaloric basis (50 kcal/d) with a lowered amount of dextrose; and 3) a control group, which received dextrose perfusion and had free access to chow. A subgroup of D/aa/L rats (n = 6) received a TPN solution containing homocysteine. After 5 days of TPN, bile was collected during 2 hours. In liver homogenates, GSH, thiobarbituric acid reactive substances (TBARS), and carbonyl content of proteins (Prot-CO) were measured to test the level of oxidative stress and hepatic lipid and protein oxidation. RESULTS: After TPN, bile flow was significantly lower in the D/aa group than in the control group. Addition of lipids further decreased bile flow. Addition of homocysteine to TPN with lipids significantly increased bile flow. Aspartate aminotransferase increased significantly in both TPN groups compared with the control group. gamma-Glutamyl transpeptidase was not different among TPN groups. An increased hepatic lipid oxidation was demonstrated by TBARS level in both TPN groups when compared with the control group. However, the liver GSH contents were not different. Protein oxidation was also significantly increased by TPN. The addition of homocysteine to TPN solution increased bile flow without liver injury or changes of lipid and protein oxidation. DISCUSSION: This study shows that TPN administered to rats induces a decrease of bile flow and an oxidative stress but that the two changes are not directly correlated. Addition of lipids further impairs bile flow but does not increase the occurrence of liver injury. Consequently, it seems more likely that TPN primarily induces a cholestatic effect that in turn induces an oxidative stress rather than inducing an oxidative stress that leads to cholestasis. However, an association of both mechanisms is not totally excluded.

Animals↗

Orthotopic liver transplants in children: change in hepatic venous Doppler wave pattern as an indicator of acute rejection.

PURPOSE: To determine whether a change in hepatic venous flow pattern can be seen during hepatic graft rejection and if it is reversible with treatment. MATERIALS AND METHODS: Thirty-nine children received 42 liver allografts during a 10-year span. Doppler ultrasonographic (US) recordings of hepatic venous wave patterns were reviewed. Nine children (ten grafts) with continuously monophasic flow were not included in the study. Changes from triphasic to monophasic flow were recorded and correlated with clinical findings in all 30 patients and biopsy findings in 25. Biopsy results were compared with US data recorded within 24 hours of biopsy. Standard statistical tests were conducted to assess value of Doppler US in diagnosis of graft rejection. Significance was assessed with chi(2) statistics. RESULTS: Of 113 Doppler US recordings in 30 children, 74 showed an episode of change in flow from triphasic to monophasic in 27 patients; biopsy correlation existed for 39 episodes. Thirty-five episodes were due to acute graft rejection (true-positive results). Thirty-nine episodes were due to a variety of pathologic causes (determined with biopsy results for 12 and by clinical means for 27) (false-positive results). Thirty-six assessments were true-negative (US and biopsy results negative for rejection); three were false-negative. When US results were evaluated against clinical and biopsy data, analysis revealed that change to monophasic flow predicted rejection with sensitivity of 92% (35 of 38) and specificity of 48% (36 of 75). Negative predictive value of evidence of persistent triphasic flow was 92% (36 of 39). In the subgroup of US findings with biopsy correlation, specificity increased from 48% (36 of 75) to 75% (36 of 48). It was zero (0 of 27) for the group with clinical correlation only. CONCLUSION: Change of hepatic venous flow pattern from triphasic to monophasic is sensitive but nonspecific for detection of graft rejection. Evidence of persistent triphasic flow helps eliminate the possibility of graft rejection with a high negative predictive value.

Adolescent↗

Hepatic vein Doppler studies: variability of flow pattern in normal children.

BACKGROUND: Loss of triphasicity of hepatic venous flow on Doppler US has been correlated with hepatic parenchymal disease such as cirrhosis and graft rejection in adults. OBJECTIVE: To document physiological variations of hepatic vein (HV) flow patterns in normal children of different age groups, the influence of age, sex, body position, site of measurements within a given vein, exercise and food intake. Also, to document the reproducibility of the Doppler US findings in the three major HVs, in order to establish the limits of normal flow against which to assess liver pathology giving rise to abnormal flow pattern. MATERIALS AND METHODS: Thirty-two children, divided into four age groups: less than 1 year, 1-5 years, 5-12 years and 12-16 years, with four boys and four girls in each group, underwent repeated US examinations of their HVs. The HV flow pattern was recorded as triphasic = 4, diphasic = 3, monophasic = 2 or uninterpretable = 1 at three sites in each vein: peripheral, middle and proximal in the supine position in the fasting state. One recording was then obtained in the midportion of each vein in the sitting position, another one after exercise, then after a meal and lastly one by a second radiologist. Statistical analysis of variance was done of each variable alone, in combination two by two and three by three. RESULTS: HV flow pattern was different from one vein to another in the majority of the children, the right HV having the least triphasic flow. Age was highly significant, the HV flow being less triphasic in young children. Sex and position were significant for the right HV only, which was the most difficult to examine. Exercise and food intake did not change the triphasicity of flow. CONCLUSIONS: HV flow pattern differs with age and can differ from one HV to another within an apparently normal liver. Interpretation is generally reproducible from one radiologist to another. A difference of sex, seen mostly for the right HV, may be due to unfavourable Doppler angle and difficulty of interpretation. The site of measurements within a given vein, body position, exercise and food intake do not influence the triphasicity of HV flow.

Adolescent↗