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Biomedical subjects

G Zacchello

Publications and source records attributed to G Zacchello.

At least 73 records · Page 4Linked to original sources

Exercise tolerance after anaemia correction with recombinant human erythropoietin in end-stage renal disease.

The aim of this study was to evaluate the effect of correction of chronic anaemia on the physical performance and the cardiovascular response to effort in children with end-stage renal disease (ESRD) maintained by haemodialysis. Seven patients (mean age 13.9 years) underwent triangular-type treadmill exercise testing before [haemoglobin (Hb) 6.3 +/- 0.9 g/dl] and after (Hb 11.2 +/- 1.2 g/dl) anaemia correction with recombinant human erythropoietin (rHuEPO). After treatment, the work-load reached, the peak oxygen uptake and average ventilatory anaerobic threshold (VAT) values were significantly increased (P less than 0.01, P less than 0.001, P less than 0.05 respectively). VAT values, expressed as a percentage of normal values, increased from 55.7 +/- 16.6% to 82.4 +/- 21%. This improvement correlated well with the increase in Hb (r = 0.79). Oxygen pulse also increased significantly, when tested after anaemia correction. In conclusion, these data demonstrate that when the anaemia of children with ESRD is corrected with rHuEPO, there is a clear improvement in aerobic work capacity and effort tolerance.

Adolescent↗

Benefits and risks of anemia correction with recombinant human erythropoietin in children maintained by hemodialysis.

Ten children with renal failure (age range 2 years 6 months to 18 years 9 months; median 11 years 10 months), maintained by long-term hemodialysis, had successful correction of their anemia after intravenous administration of recombinant human erythropoietin in a dosage escalating every 2 weeks (75 to 150 to 300 to 450 IU/kg/wk). Mean hemoglobin concentration increased from 6.4 +/- 0.9 to 11.5 +/- 1.0 gm/dl. Blood cell counts used to evaluate the correction of anemia were done after dialysis; this was especially important for children less compliant with water restriction. The higher hemoglobin concentration resulted in improvement of the quality of life, a greater tolerance for physical effort (exercise tolerance doubled and the ventilatory anaerobic threshold increased significantly), correction of some subclinical central nervous system abnormalities detected by evoked potentials testing, and reduction of bleeding time. Few side effects were noted; severe hypertension developed in one patient when postdialysis hematocrit was only 28%, and there were two episodes of hypertransaminasemia with no other evidence of liver dysfunction. We conclude that in children with renal failure the use of recombinant human erythropoietin to correct anemia is safe and strongly advisable, because of the resolution of many of the symptoms correlated with anemia.

Adolescent↗

Antenatal aminophylline and steroid exposure: effects on glomerular filtration rate and renal sodium excretion in preterm newborns.

Creatinine clearance and renal sodium excretion were measured consecutively in three groups of 12 premature infants (gestational age less than or equal to 35 weeks) whose mothers had received either steroids or aminophylline, or steroids and aminophylline before delivery. We found no significant differences for plasma and urine creatinine and its clearance in the groups considered. The steroid group presented urine osmolality and urine/plasma osmolality ratio significantly higher than among the other groups. Furthermore, urine potassium excretion increased, and urine sodium and sodium fractional excretion were reduced. Aminophylline exposure did not interfere with the hydrosaline equilibrium nor with renal function of the preterms at birth. Our results reconfirm that corticosteroid hormones play an important part in the fetal renal maturation process, inducing a precocious maturation of the tubular Na(+)-K+ ATPase enzymatic system, that is substantially unmodified by aminophylline exposure. However, due to the prolonged half-life of aminophylline in prematures, it seems reasonable to verify the coupling of tubular and glomerular functions also in the following days of life.

Aminophylline↗

Urinary beta-2-microglobulin excretion in prematures with respiratory distress syndrome.

Urinary concentrations of beta 2-microglobulin (beta 2M) were studied in 25 prematures (less than or equal to 35 weeks) with respiratory distress syndrome (RDS), divided into two groups (group 1: ventilation greater than or equal to 2 days; group 2: oxygenotherapy less than or equal to 4 days), to assess the value of beta 2M in the detection of tubular damage in relation to the severity and management of the respiratory disease. The data were compared with those obtained from 10 healthy controls, matched for birth weight and gestational age. Measurements of beta 2M were made on urine collected on days 1, 3, and 5 until the recovery phase of RDS was reached. Urinary beta 2M values for infants with RDS were increased on days 1 and 3, with respect to the controls, and significantly increased in the ventilated group (8,814 +/- 4,768 vs. 2,594 +/- 3,231 micrograms/l, p less than 0.005 and 7,624 +/- 6,264 vs. 2,762 +/- 2,316 micrograms/l, p less than 0.05, respectively). Serum sodium and creatinine, creatinine clearance, fractional tubular sodium excretion and renal function index on day 1 were similar in prematures with or without RDS. However, the ventilated newborns presented higher urinary sodium excretions. On the 5th day, no significant differences in urinary beta 2M were found among the groups. The elevated levels of urinary beta 2M in the acute phase of RDS and in the more severe lung disease indicate the existence of subclinical tubular dysfunction, probably secondary to hypoxic stress and to negative hemodynamic effects of ventilatory management.

Humans↗

Exercise tolerance in end-stage renal disease.

The cardiorespiratory and metabolic response to exercise was evaluated in children with end-stage renal failure maintained on haemodialysis. Eight patients (haemodialysis group), 4 boys and 4 girls, with a mean age of 13.4 +/- 3.6 years (range 9.4-18.6 years) and haemoglobin levels ranging from 5.3 to 7.6 g/dl and 16 healthy children (control group) performed a progressive exercise testing on a treadmill. Gas exchange was simultaneously monitored. The mean ventilatory anaerobic threshold of the haemodialysis group, expressed as a percentage of the reference values, was 59.1 +/- 18.2%, and their maximum work load (29.9 +/- 19 W) was about one fourth of that reached by the control group (113.3 +/- 51.6 W). Ventilatory anaerobic threshold values in the haemodialysis group significantly correlated with blood haemoglobin levels, but not with creatinine and parathyroid hormone concentrations. We, therefore, conclude (1) that children maintained on chronic haemodialysis have a marked reduction in aerobic working capacity and (2) that the major cause for this limitation appears to be the reduced haemoglobin concentration.

Adolescent↗

Posttransfusion hemoglobinuria and myoglobinuria in neonates.

Posttransfusion positive dipsticks for occult blood do not differentiate hemoglobinuria from myoglobinuria, relatively common events in infants admitted to the neonatal intensive care unit. We studied posttransfusion plasma and urine hemoglobin and myoglobin in relation to occult blood positivity in the urine dipsticks, in 48 consecutive transfusions with packed RBC (28 neonates, birth weight 850-3,700 g, postnatal age 3-167 days). Urine dipsticks show a low sensitivity for detecting hemoglobin and also undervalue myoglobin, both possible in different amounts in the plasma and urine of ill neonates. However, posttransfusion occult blood positive urine dipsticks due to myoglobinuria are present in 10% of transfused neonates.

Blood Transfusion↗

Plasma arginine vasopressin, diuresis, and neonatal respiratory distress syndrome.

The pathogenesis of the diuresis that precedes the recovery from respiratory distress syndrome (RDS) in preterm infants has not been clearly delineated. To define the role of Arginine Vasopressin (AVP) or Antidiuretic Hormone in the diuretic phase of RDS, we obtained plasma AVP levels (radioimmunoassay) and sequential time-urine-plasma collections during the first, the third and the fifth days of life in twelve premature ventilated newborns. AVP levels were persistently elevated (12.7 +/- 7.6; 9 +/- 4.7 and 10.4 +/- 6.6 pg/ml, respectively) despite normal plasma sodium and osmolality. Maximum diuresis (output/intake greater than 0.72) occurred at 72 hours and preceded the improvement in FiO2/PaO2, significant on 5th day (p less than 0.01), and associated with a 10.6% decrease in body weight. These results suggest a nonosmotic release of AVP in ventilated newborns, and show a hypervasopressinemia unrelated to the diuresis associated with the recovery phase of RDS.

Arginine Vasopressin↗

Neurogenic vesico-urethral dysfunction in children with cerebral palsy.

20 children with severe cerebral palsy and history of urinary incontinence and recurrent urinary infection underwent radio--and neuro-urologic evaluation. Vesico-ureteral reflux was found in 7 patients. In 9, who had presented episodes of urine sub-retention, a urodynamic study demonstrated detrusor muscle hyperreflexia in all, deficit of vesicourethral sensation in 5 and detrusor-sphincter dyssynergia in 2. These functional findings are compatible with an upper motor neuron lesion, and may be the cause of episodes of altered bladder emptying, and consequently, urinary infection.

Adolescent↗

Further definition of lipid-lipoprotein abnormalities in children with various degrees of chronic renal insufficiency.

We characterized the lipid-lipoprotein abnormalities encountered in a series of 45 nonnephrotic uremic children with various degrees of chronic renal insufficiency. A mild hypertriglyceridemia associated with decreased serum high-density lipoprotein cholesterol levels was confirmed. The correlation between high-density lipoprotein cholesterol and creatinine clearance showed a power behavior with a marked decrease in high-density lipoprotein cholesterol below a creatinine clearance value of 40 ml/min/1.73 m2. A number of uremic children accumulate an abnormal population of very low-density lipoprotein particles in their plasma. On agarose gel electrophoresis these particles migrate as a slow moving pre-beta band and are clearly distinguished from the regular fast moving pre-beta very low-density lipoprotein band. This electrophoretic phenomenon has been called double pre-beta lipoproteinemia. The prevalence of double pre-beta lipoproteinemia increased significantly with the degree of impairment of renal function, reaching highest figures in patients on hemodialysis. Accordingly, the very low-density lipoprotein cholesterol/triglyceride ratio also was significantly increased. The double pre-beta lipoproteinemia phenomenon was not detected in any of the control, nonuremic subjects. The clinical importance of double pre-beta lipoproteinemia in uremic plasma is related to its possible atherogenic role.

Adolescent↗

Malonyl-CoA abnormal inhibition of residual enzyme activity in carnitine palmitoyltransferase deficiency.

The residual enzyme activity in tissues of a 6-year-old boy with myoglobinuria and carnitine palmitoyltransferase (CPT) deficiency was studied with malonyl-CoA, a specific inhibitor of CPT-I in rat tissues. In this patient the enzyme deficiency was limited to the CPT fraction insensitive to malonyl-CoA, since the residual activity was an increased amount of CPT sensitive to the inhibitor. CPT sensitivity to malonyl-CoA was also assayed in human liver mitochondria, and inhibition was similar to that found in rat liver. Moreover, comparative data on human liver mitochondria and biopsy specimens showed that, after freeze-thawing and homogenization, CPT sensitivity to malonyl-CoA was decreased in both these preparations, indicating that studies of CPT inhibition by malonyl-CoA in homogenates of frozen tissues may be equated to those in homogenates of frozen mitochondria.

Acyl Coenzyme A↗

Hepatitis B virus replication in acute glomerulonephritis with chronic active hepatitis.

A 3 year old boy who had chronic active hepatitis type B with features of ongoing liver damage and active virus replication, developed acute membranous glomerulonephritis two years after the clinical onset of liver disease, when both hepatitis B e antigen and antibody were detectable in serum. After withdrawal of short term steroid treatment and resolution of hepatitis B virus replication, both glomerulonephritis and chronic hepatitis went into remission. Some months later hepatitis B surface antigen was no longer found in serum.

Acute Disease↗

Evaluation of glomerular and nonglomerular hematuria by phase-contrast microscopy.

Glomerular and nonglomerular origins of hematuria may be identified by assessment of the shape and size of the excreted red blood cells. We examined 380 urine specimens from 179 children with hematuria (greater than or equal to 3500 RBC/minute) with phase-contrast microscopy. In 106 cases, the cause was known; the results agreed with the clinical, histologic, and laboratory diagnosis in 63 of 65 subjects (97%) with glomerulopathies and in 39 of 41 (95%) with nonglomerular hematuria. Casts were found in 54% of the specimens from the children with definite glomerular hematuria. Phase-contrast microscopic examination of red blood cells in the urine is a simple, inexpensive, and noninvasive technique that permits an accurate distinction between glomerular and nonglomerular bleeding in pediatric patients.

Adolescent↗

Juvenile renal stone disease: a study of urinary promoting and inhibiting factors.

Urinary excretion of the most widely studied renal stone promoting (calcium, oxalate, uric acid and phosphate) and inhibiting (citrate, magnesium, pyrophosphate and glycosaminoglycans) factors, as well as the Tamm-Horsfall mucoprotein, was evaluated in 14 children with idiopathic calcium nephrolithiasis, 6 children with renal stone disease secondary to excretory malformations and 19 normal controls. No statistically significant differences in urinary excretion of promoting and inhibiting factors were found in children with idiopathic calcium nephrolithiasis but the relationship between promoting and inhibiting factors was changed as shown by an abnormal ratio of oxalate/citrate X glycosaminoglycans. This finding suggests that there is an imbalance between promoting and inhibiting factors in children with idiopathic calcium nephrolithiasis, and it is not detected by assay of each single substance.

Adolescent↗

Simple estimate of creatinine clearance from plasma creatinine in neonates.

Thirteen newborn infants, 8 preterm and 5 term, with either mild or serious neonatal asphyxia were studied. From the first 24 hours of life to day 13, glomerular filtration rate (GFR) estimated by creatinine clearance was compared with the values obtained using Schwartz's formula: GFR (ml/min per 1.73 m2) = 0.55 x length (cm)/plasma creatinine (mg/100 ml). Both in term and preterm infants, values of formula-calculated creatinine clearance were slightly higher than values obtained by the classical method; nevertheless the data show significant correlations, respectively r = 0.867 and r = 0.795 (P less than 0.001). This formula provides an adequate estimation of neonatal creatinine clearance (a marker for GFR) directly from plasma creatinine provided that body length is taken into consideration. The necessity for urine collection and the associated problems are thus obviated. The simplicity of Schwartz's formula permits easy monitoring of renal function, especially in neonatal asphyxia in which the risk of developing renal failure is great.

Asphyxia Neonatorum↗

Cystinuria in children.

7 children, 20 months to 11 years old, with cystinuria and renal calculi were studied. Surgical treatment and alpha-mercaptopropionylglycine (MPG) gave satisfactory results in 5 children. The causes of the recurrences in the other 2 children are discussed. MPG therapy is effective but can cause a nephrotic syndrome at a dose of more than 50 mg/kg/day. A cystinuria of less than 200 mg/day cannot always be considered safe in children. The alkalinization and dilution of urine remain extremely important in the treatment of cystinuria.

Amino Acids, Sulfur↗