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Biomedical subjects

P Robitaille

Publications and source records attributed to P Robitaille.

At least 19 recordsLinked to original sources

Plasma homocysteine concentration in children with chronic renal failure.

Hyperhomocysteinemia, a risk factor for vascular disease, is commonly found in adult patients with end-stage renal disease. Major determinants of elevated plasma homocysteine levels in these patients include deficiencies in folate and vitamin B12, methylenetetrahydrofolate reductase (MTHFR) genotype and renal function. Little information is available for children with chronic renal failure (CRF). The prevalence and the factors that affect plasma homocysteine concentration were determined in children. Twenty-nine children with various degrees of CRF (15 were dialyzed, 14 were not dialyzed) were compared with 57 age- and sex-matched healthy children. Homocysteine concentrations were higher in patients than controls (17.3 micromol/l vs 6.8 micromol/l, P<0.0001) and hyperhomocysteinemia (>95th percentile for controls: 14.0 micromol/l) was seen in 62.0% of patients and 5.2% of controls. Folate concentrations were lower in patients (9.9 nmol/l) than controls (13.5 nmol/l), P<0.01. Vitamin B12 was similar in patients (322 pmol/l) and controls (284 pmol/l). Dialyzed patients have a higher prevalence of hyperhomocysteinemia than nondialyzed patients (87% vs 35%). Dialyzed patients with MTHFR mutation have higher plasma homocysteine (28.5 micromol/l) than nondialyzed patients with the mutation (10.7 micromol/l), P<0.002. In our study, differences between controls and patients in plasma homocysteine concentrations are observed when age is greater then 92 months, folate less than 21.6 nmol/l and vitamin B12 less than 522 pmol/l. Our study shows that hyperhomocysteinemia is common in children with CRF and is associated with low folate and normal vitamin B12 status, compared to normal children. Among the patients, the dialyzed patients with the MTHFR mutation are particularly at risk for hyperhomocysteinemia. Further studies are needed to investigate therapeutic interventions and the potential link with vascular complications in these patients.

Adolescent↗

Cerebral vascular complication and hyperhomocysteinemia in a cystinotic uremic child.

We report a 13-year-old girl with nephropathic cystinosis on chronic peritoneal dialysis who presented with two episodes of stroke. Laboratory evaluation showed severe hyperhomocysteinemia (108 mumol/l). Further testing revealed that she was homozygous for the thermolabile variant of the methylenetetrahydrofolate reductase (MTHFR) gene. Treatment with folic acid and vitamin B12 lowered plasma homocysteine to less than 20 mumol/l. No further episodes of stroke occurred over a follow-up of 12 months. Homocysteine levels should be measured in patients with chronic renal failure, since simple and safe treatment with folic acid and vitamin B12 is effective in lowering the plasma homocysteine level in patients with the thermolabile MTHFR allele.

Adolescent↗

Circulating inflammatory cytokine levels in hemolytic uremic syndrome.

Experimental data suggest that the host's inflammatory response is involved in the pathophysiology of verotoxin-producing Escherichia coli (VTEC)-associated hemolytic uremic syndrome (HUS). We compared the circulating levels of pro- [interleukin (IL)-6, IL-8] and anti-inflammatory [IL-10 and IL-1 receptor antagonist (Ra)] mediators on enrollment among children with HUS due to E. coli O157:H7, according to the severity of renal dysfunction. The latter was evaluated by the occurrence of oligoanuria, the requirement for dialysis, and a glomerular filtration rate (GFR) </=80 ml/min per 1. 73 m(2) measured 1 year later. Increased levels of IL-6 (P<0.0001), IL-10 (P<0.0001), and IL-1Ra (P<0.07) were found among patients with HUS compared with normal controls. Children with severe renal dysfunction also had tenfold increased levels of IL-6 and higher concentrations of IL-10 and IL-1Ra. Both the IL-6/IL-10 (4.9+/-8.3 vs. 0.5+/-0.4, P=0.01) and the IL-6/IL-1Ra ratios (0.10+/-0.20 vs. 0. 01+/-0.01, P=0.04) were significantly increased. GFR correlated well with IL-6 levels, IL-6/IL-10 and IL-6/IL-1Ra ratios. Our data demonstrate that the inflammatory response of the host is associated with the severity of renal dysfunction during classic HUS. An imbalance between the pro- and the anti-inflammatory responses may be involved in the pathophysiology of VTEC-associated HUS.

Child↗

Inflammatory mediators in Escherichia coli O157:H7 hemorrhagic colitis and hemolytic-uremic syndrome.

BACKGROUND: Recent experimental data suggest that the inflammatory response of the host to verotoxin and/or lipopolysaccharides of Escherichia coli is involved in the pathophysiology of verotoxin-producing E. coli (VTEC) infections. METHODS: We measured the circulating concentrations of cytokines [TNF-alpha, interleukin (IL)-1-beta, IL-1 receptor antagonist (Ra), IL-6, IL-8, IL-10] and soluble leukocyte adhesion molecules (L-selectin, P-selectin, E-selectin, intracellular cell adhesion molecule-1, vascular cell adhesion molecule-1) by sandwich enzyme-linked immunosorbent assay among (1) normal controls (n = 12), (2) disease controls with hemorrhagic colitis (HC) not associated with VTEC infections (n = 57), (3) patients with uncomplicated HC caused by E. coli O157:H7 (n = 30), and (4) children with hemolytic-uremic syndrome (HUS) (n = 28). Patients with HUS were matched with children who presented an uncomplicated HC caused by E. coli O157:H7 for the time interval elapsed between the onset of HC and that of blood sample collection. RESULTS: Concentrations of TNF-alpha and IL-1-beta were undetectable. Children with HUS were characterized by increased amounts of IL-6 and IL-8, lower values of soluble L-selectin as well as increased levels of IL-10 and IL-1Ra. The circulating concentrations of IL-1Ra were higher among children with O157:H7 HC who subsequently developed HUS. CONCLUSIONS: Increased pro- and antiinflammatory cytokine responses are produced by the host during the development of HUS among children with VTEC infections. Further studies are needed to determine their relative contribution to the pathophysiology of classic HUS.

Cell Adhesion Molecules↗

Study of psychosocial parameters related to the survival rate of renal transplantation in children.

The purpose of the present study was to assess the effect of intelligence, schooling, psychomotor, emotional, and social status on renal graft survival in children. Sixty-two cadaver renal transplant recipients were evaluated retrospectively and the influence of sex, age, weight, and the use of cyclosporin A (CyA) on the success rate of the graft from 1 to 5 years later was analyzed. Psychological and social scores were devised and included as factors predictive of survival of the graft. Univariate analysis showed that the following variables predicted renal graft survival: the use of CyA (P = 0.0002), pre-transplant dialysis (P = 0.04), weight at the time of transplantation (P = 0.072), and psychological scores (P = 0.064). Association analysis demonstrated that pre-transplantation dialysis was only a chance association and therefore the parameter was discarded. Multivariate analysis showed that the predictive parameters were the use of CyA, sex, weight in kilograms, and the psychological score. An equation was then derived from variables that predict the probability that a specific patient's graft will survive more than t months. This equation is the estimated survival distribution function and is as follow: S (t) = Exp {-Exp[-(0.8882x1 - 1.827x2 + 0.037x3 - 0.1746x4) + ln t - 4.7862]} where S (t) = the survival at t months post transplantation, x1 = sex (male 1, female 2), x2 = CyA (yes 1, no 2), x3 = weight in kilograms, and x4 = psychological score. The major impact of psychological factors on renal graft survival was surprising.

Adolescent↗

Pancreatic injury in the hemolytic-uremic syndrome.

In a retrospective review of 241 cases with hemolytic-uremic syndrome, there was evidence of pancreatic involvement in 2 patients, abnormal ultrasounds in 4 patients, and pancreatic injury in 3 of 8 patients undergoing autopsy. Pancreas ultrasound examination, available in 134 cases, was very valuable in identifying those with pancreatic injury.

Child↗

Renovascular hypertension in children: curability predicted with negative intrarenal Doppler US results.

PURPOSE: To assess whether intrarenal Doppler ultrasound (US) enables prediction of the outcome of renovascular hypertension in a pediatric population. MATERIALS AND METHODS: A prospective study of 29 children with renin-mediated hypertension was performed. In these patients, intrarenal Doppler US was performed before angiography. Doppler US and angiographic findings were compared with patient outcome with respect to treatment required and blood pressure (BP) status after therapy. Cure was defined as a normal BP without medication. RESULTS: Intrarenal Doppler US was positive in 15 patients (52%), group 1, and negative in 14 patients (48%), group 2. In 10 patients (67%) in group 1, the severity of the vascular lesion precluded permanent cure. Cure was achieved in all patients in group 2, except for patients with neurofibromatosis. Thus, there was a statistically significant association (P < .05) between cure and a negative Doppler US result. CONCLUSION: In children with renovascular hypertension, a negative Doppler US result enables the prediction that a cure is more likely to be achieved with endovascular therapy or surgery.

Angioplasty, Balloon↗

Serum guanidino compound levels in uremic pediatric patients treated with hemodialysis or continuous cycle peritoneal dialysis. Correlations between nerve conduction velocities and altered guanidino compound concentrations.

Serum levels of twelve guanidino compounds (GCs) and nerve conduction velocities were determined in a dialyzed renal insufficient pediatric population. Two dialytic groups were considered: one subjected to hemodialysis (HD, 11 patients) and one subjected to continuous cycle peritoneal dialysis (CCPD, 13 patients). Before HD, marked increases were found for guanidino-succinic acid (207 times), methylguanidine (> or = 67 times), argininic acid (24 times), creatinine and alpha-N-acetylarginine (18 times) and guanidine (> or = 14 times) when compared to controls. Important significant increases were still present after an HD session for guanidinosuccinic acid (49 times), methylguanidine (34 times), creatinine (7 times) and alpha-N-acetylarginine and guanidine (6 times). After HD, creatine, arginine and homoarginine were lower than in controls. All GCs, with the exception of creatine, decreased significantly after a single HD session with percentage decrease ranging between 40% (for arginine) and 77% (for guanidinosuccinic acid). Creatine decreased in a statistically nonsignificant manner by 48%. Marked increases were found in the CCPD group for guanidinosuccinic acid (114 times), alpha-N-acetylarginine (12 times), argininic acid (15 times), creatinine (22 times), guanidine (> or = 11 times) and methylguanidine (> or = 48 times). Concentrations of guanidinosuccinic acid before and after HD and in CCPD were comparable to those reported to be toxic in vitro and in vivo. No clinical or electrophysiological indications of polyneuropathy were observed in our population. Sensory and motor nerve conduction studies showed few abnormalities apart from a significant correlation between argininic acid concentration or guanidine levels and the peroneal nerve conduction velocity in the CCPD-treated group.

Adolescent↗

Transient renal artery stenosis in infants: myth or reality?

We describe two infants with bilateral renal artery stenoses and severe hypertension. Adequate control of blood pressure was achieved by medical management. Endoluminal balloon dilatation of the renal arteries had been deferred because of their small size. On follow-up it was noticed that blood pressure had become progressively easier to control, with lesser amounts of antihypertensive medication. In fact, medication could be completely discontinued and blood pressure remained normal. On repeat arteriogram, bilateral renal artery stenoses had almost resolved in both patients. The etiology of the stenoses was not established in these patients. However, regardless of etiology, the transient nature of hypertension and renal artery stenoses in these two cases demonstrates that patient medical management of hypertension in infants can be a valid therapeutic option and occasionally obviate the need for unnecessary risky procedures.

Antihypertensive Agents↗

A tiny renal renin-secreting tumor.

A small 5 mm renal renin-secreting tumor is described in a child. Suggestions are made to circumvent the difficulties in investigating such cases. It is stressed that the diagnosis is probably often missed especially in the case of very small tumors.

Adenocarcinoma↗

Renal vein thrombosis in children: evidence of early flow recovery with Doppler US.

PURPOSE: To characterize renal arterial and venous Doppler signals in pediatric renal vein thrombosis (RVT) and to study changes in the circulation in the months following the acute event. MATERIALS AND METHODS: Ten patients with proved acute RVT (eight infants and two boys with renal allografts) were studied with serial Doppler ultrasonography (US) of the inferior vena cava and the main renal and intrarenal veins and arteries. RESULTS: The resistance index in the affected vessel was increased by 10% compared with that of the normal side in patients with unilateral RVT. Only the allografts had reversed diastolic flow. Venous flow, which was detected around the thrombus and in intrarenal veins in all native kidneys, was absent during the 1st week in the transplanted kidneys but reappeared thereafter in one. Perirenal collateral vessels were demonstrated with color Doppler US in one baby. Seven of eight native kidneys atrophied, and the allografts failed. CONCLUSION: Classic Doppler signs of RVT--absent venous flow and reversed diastolic arterial flow within the kidney--were present in only the acute phase in transplanted kidneys. These signs are unreliable in RVT of native kidneys.

Child↗

Decreased hospitalization and increased height velocity in focal segmental glomerulosclerosis responsive to ciclosporin A.

Eleven pediatric patients with nephrosis and focal segmental glomerulosclerosis were treated with long-term (8-38 months) ciclosporin A in combination with steroids. All had abnormal height-velocity curves and multiple hospitalizations for complications of nephrosis. Eight patients attained remission with a dramatic improvement in growth and decrease in necessity for hospitalization for therapy of nephrosis complications, while maintaining adequate renal function. Three nonresponders developed end-stage renal disease. Long-term ciclosporin A therapy may be of benefit in steroid-resistant nephrosis in childhood.

Child↗

Hemolytic-uremic syndrome: intrarenal arterial Doppler patterns as a useful guide to therapy.

Seventeen children with acute renal failure due to the hemolytic-uremic syndrome were examined with duplex Doppler ultrasound. Serial measurements of intrarenal arterial pulsatility were obtained by means of the Pourcelot index. These were compared with daily urine volume, both during the phase of renal failure (during which most of the children were undergoing peritoneal dialysis) and during recovery of renal function. During oliguria or anuria there was either no intrarenal arterial flow (ie, absent Doppler shifts), or absent, reversed, or markedly reduced diastolic flow. Within 24-48 hours after diastolic Doppler shifts returned to normal, diuresis occurred. The Doppler examination enabled prediction of recovery and allowed dialysis treatment to be abbreviated or, in some cases, canceled.

Acute Kidney Injury↗