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Biomedical subjects

D Hébert

Publications and source records attributed to D Hébert.

At least 19 recordsLinked to original sources
PubMed2000

Polyuria and proteinuria in cystinosis have no impact on renal transplantation. A report of the North American Pediatric Renal Transplant Cooperative Study.

Because cystinotic patients are polyuric and may have severe proteinuria, each of which is a potential risk factor for graft thrombosis, preemptive transplantation for them is questionable. The objectives of this study were to characterize the changes in urine volume and protein excretion at various stages of cystinosis, determine whether there is serologic evidence of hypercoagulability, and review the clinical experience in renal transplantation in cystinotic children. The records of cystinotic patients followed at the Montreal Children's Hospital between 1992 and 1998 were reviewed. Urinary volume, protein excretion, and coagulation markers were collected to determine the glomerular filtration rate (GFR) >50 ml/min/1.73 m2, <20 ml/min/1.73 m2, before and after starting dialysis. In addition, graft failure and graft thrombosis rates were obtained from the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS) database. Urinary volume and protein excretion remained elevated throughout different phases of the disease. Coagulation factors were within normal limits for all patients. In the NAPRTCS database there were four thromboses among the 114 patients transplanted cystinotic patients. All these occurred in cadaveric grafts and only one occurred after preemptive transplantation. Despite polyuria and severe proteinuria, children with cystinosis do not appear to be at an increased risk of graft failure or graft thrombosis.

Child↗
PubMed2000

Nitroglycerin rebound associated with vascular, rather than platelet, hypersensitivity.

OBJECTIVES: The purpose of this study was to determine whether acute withdrawal of nitroglycerin (NTG) during hemodynamic tolerance is associated with platelet hypersensitivity. BACKGROUND: Nitroglycerin is an effective antianginal medication but its use is limited by the development of tolerance and rebound. We have previously demonstrated a sustained inhibition of platelet function during continued use of NTG, but whether cessation of NTG is associated with an increase in platelet function that may contribute to rebound is unknown. METHODS: Normal porcine aortic media were exposed to flowing arterial blood from pigs (n = 8) treated continuously with NTG patches (Nitrodur 0.8 mg/h) for 48 h. Platelet function, blood pressure and the responses to angiotensin II infusion were evaluated before, during and after NTG treatment. RESULTS: Mean arterial pressure fell by 15% after 3 h of treatment compared with control, returned to baseline by 48 h and increased significantly 2 h after drug removal. Autologous 51Cr-labelled platelet deposition on the aortic media was reduced by 30% after 48 h of continuous NTG administration compared with baseline (p = 0.02) and remained decreased 2 h after cessation of NTG therapy. Platelet aggregation to thrombin decreased in parallel to the decrease in platelet deposition. Blood pressure increase after intravenous injection of 10 microg of angiotensin II was blunted during treatment with NTG but increased significantly 2 h after cessation of nitrate therapy when compared with baseline. CONCLUSIONS: Supersensitivity of the vessel wall to vasoconstrictors such as angiotensin 11, but not platelet hyperactivity, may contribute to the rebound phenomenon after acute nitrate withdrawal.

Angiotensin II↗
PubMed1999

Lymphoproliferative disorders after organ transplantation in children.

BACKGROUND: After organ transplant, patients are at risk of posttransplant lymphoproliferative disorders (PTLD). The purpose of this study was to analyze 26 pediatric cases of PTLD observed at our institution between 1988 and 1996, and to evaluate the validity of the Society for Hematopathology Workshop (SHPW) 1997 classification in our patient population. METHODS: Charts were reviewed for analysis of incidence, clinical course, and outcome. Tissue samples were classified by a pathologist according to SHPW recommendations. RESULTS: By morphology, 20 were monomorphic, 5 polymorphic, and 1 hyperplastic. Assessment of lineage by morphology, molecular studies, and immunophenotyping did not correlate in six cases. By immunophenotyping, 12 were B cell, 4 T cell, 8 mixed B/T cells, and 2 undetermined. The 20 patients evaluable for treatment efficacy were treated with various therapeutic combinations, including immunosuppressive drug reduction, acyclovir/ganciclovir, interferon-alpha, immunoglobulins, surgery, and local irradiation. No patient received systemic chemotherapy. Thirteen patients achieved complete remission and 3, partial; 1 died 5 days after starting therapy, and 3 of progressive disease. Adverse prognostic factors included low platelet or neutrophil counts; stage III-IV and SHPW morphology were marginally significant. CONCLUSIONS: The majority of patients eligible for treatment can be cured with immunosuppressive drug reduction and antiviral drugs, along with surgery and irradiation when indicated. Systemic chemotherapy or innovative approaches may have a role in unresponsive cases. Morphologic SHPW grouping is feasible and seems to have clinical relevance. However, correlation with clonality and immunophenotyping is not always possible, necessitating modifications including segregation of descriptive morphology from clonality and cell origin.

Adolescent↗
PubMed1999

Complications of gastrostomy feeding in children receiving peritoneal dialysis.

Gastrostomy tube (g-tube) feeding is recognized to improve the nutritional delivery to children with end-stage renal disease. A retrospective study was undertaken assessing the complications of g-tube feeding in children receiving peritoneal dialysis (PD). Twenty-three patients, mean age 3.8+/-3.2 years received PD and g-tube feeding for 758 patient-months, with 127 patients receiving PD for 1,969 patient-months used as controls. Peritonitis occurred every 18.4 patient-months in controls and 7.8 patient-months in those with a g-tube. Peritonitis occurred every 6.0 patient-months before and 8.1 patient-months after g-tube insertion in those undergoing g-tube insertion on PD. PD catheter exit site infection (PDESI) occurred every 18.7 patient-months in controls and 16.8 patient-months in those with a g-tube. PDESI occurred every 126 patient-months before and 16.2 patient-months following g-tube insertion. PD catheter replacement secondary to infection occurred every 109.4 patient-months in controls and 39.9 patient-months in those with a g-tube. It did not occur before g-tube insertion and occurred every 32.5 patient-months following insertion. Thirty-four episodes of g-tube exit site infection occurred, in 10 the same organism caused concurrent peritonitis. G-tube replacement occurred on 37 occasions. Hemodynamically significant gastrointestinal bleeding occurred in 3 patients, being terminal in 1. We conclude that, although not without risk, g-tube feeding in patients receiving PD is not contraindicated.

Bacterial Infections↗
PubMed1997

Persistent inhibition of platelets during continuous nitroglycerin therapy despite hemodynamic tolerance.

BACKGROUND: Nitroglycerin has been shown to possess antiplatelet properties in both animals and humans. Tolerance to the hemodynamic effects of nitroglycerin develops with continuous therapy, but it is unclear whether there is tolerance to its antiplatelet effect. METHODS AND RESULTS: Tolerance to nitroglycerin was studied by exposing porcine aortic media to flowing arterial blood from control pigs (n = 9) or pigs treated with continuous nitroglycerin patches (Nitro-dur, 0.8 mg/h; n = 11) at a shear rate of 3397 s-1 for 3 minutes. Relative to baseline, mean arterial pressure fell by approximately 10% at 3 and 24 hours (P < .05) but returned to baseline at 48 hours of continuous nitroglycerin treatment, whereas no significant changes were observed in control animals. Autologous 51Cr-labeled platelet deposition (x 10(6)/cm2) on the aortic media at baseline and 3, 24, and 48 hours remained stable in control animals, with mean values of 94.8 +/- 5.9, 89.4 +/- 8.3, 89.3 +/- 8.8, and 84.3 +/- 5.7, respectively. However, in pigs treated continuously with nitroglycerin for 48 hours, platelet deposition was reduced significantly at 3 (65.9 +/- 4.8), 24 (63.8 +/- 6.4), and 48 hours (56.5 +/- 7.3) of nitroglycerin treatment compared with baseline (93.1 +/- 3.6). Platelet aggregation induced by thrombin also decreased at 3 (12.4 +/- 1.3), 24 (12.6 +/- 1.7), and 48 hours (10.8 +/- 1.6) of nitroglycerin treatment compared with baseline (16.3 +/- 1.4) but remained unchanged in the control group. Also, nitroglycerin treatment increased intraplatelet cGMP at 3, 24, and 48 hours compared with baseline. CONCLUSIONS: This study demonstrates the persistent inhibition of platelet function and platelet deposition on an injured arterial wall by continuous nitroglycerin therapy despite hemodynamic tolerance.

Administration, Cutaneous↗
PubMed1997

Renal transplantation, chronic dialysis, and chronic renal insufficiency in children and adolescents. The 1995 Annual Report of the North American Pediatric Renal Transplant Cooperative Study.

The 1995 Annual Report of the North American Pediatric Renal Transplant Cooperative Study summarizes data voluntarily collected from 123 centers on 5,197 children and adolescents grouped into three cohorts: (1) patients who received renal transplants on or after 1 January 1987 (n = 3,066), (2) patients who were maintained on peritoneal dialysis (PD) or hemodialysis (HD) on or after 1 January 1992 (n = 1,488), and (3) patients treated for chronic renal insufficiency (CRI) on or after 1 January 1994 (n = 643). The transplant and dialysis information update previous registry data whereas the CRI information reflects 1st-year registry data. Three-year graft survival rates were 83% and 66% for living donor grafts and cadaver donor (CD) grafts, respectively. Triple drug maintenance therapy with prednisone, cyclosporine, and azathioprine was used by > 70% of all transplant recipients through 5 years of follow-up. The 2-year CD survival has steadily improved from 65% in 1987 to 82% in 1992. Fifty malignancies have been reported, the majority of which are lymphoproliferative disorders. The 2-year patient survival posttransplantation is 95%. Mortality rates for the youngest patients have drastically improved over the past 2 years. Approximately two-thirds of patients in the dialysis cohort are maintained on PD; automated PD remains the preferred modality. Overall, the peritonitis rate is one infection every 13.3 patient months, the frequency of infection being greatest in the youngest patients. Whereas the primary reason for dialysis modality termination is transplantation approximately 40% of the entire dialysis cohort (PD at HD) were not considered active transplant candidate Baseline CRI data revealed the most common primary diagnoses to be obstructive uropathy (24%) and aplastic/hypoplastic/dysplastic kidneys (19%). The standardized height deficit in the CRI cohort was greatest in the younger patients and those with the most impaired renal function.

Adolescent↗
PubMed1997

Compliance with cyclosporine in adolescent renal transplant recipients.

Inadequate compliance with prescribed medication regimens in children is complex and poorly understood. We measured the extent and pattern of noncompliance with cyclosporine in our adolescent renal transplant population and attempted to determine factors associated with poor compliance. After informed consent, each patient was provided cyclosporine capsules in a medication bottle equipped with an electronic monitoring device (MEMS-4) in the lid. Of the 24 patients eligible, 19 patients (8 female, 11 male) completed the study. Four (21%) patients took less than 80% of the prescribed cyclosporine doses. Five (26%) patients took drug holidays involving > or = consecutive doses. There was a trend towards improved compliance with the evening dose (88.5% vs. 93.4%, P = 0.09) and a downward trend in compliance over the course of the study (P = 0.17). None of the variables tested were found to be associated with noncompliance. Experienced physicians and nurses were able to identify 2 of the 4 individuals who were identified by MEMS as noncompliant. Additionally, 2 of the 4 noncompliance patients demonstrated low cyclosporine trough levels (< 50 ng/ml). Noncompliance with cyclosporine regimens occurs commonly in adolescent renal transplant recipients. Unexpectedly low cyclosporine levels are strongly suggestive of noncompliance, whereas other variables, including prediction by physicians and nurses intimately involved in the care, were not reflective of noncompliance.

Adolescent↗
PubMed1997

Acute acyclovir neurotoxicity in a hemodialyzed child.

A 5-year-old girl with a kidney transplant developed post-transplant Epstein-Barr virus-induced lymphoproliferative disease. She was treated with acyclovir, alpha-interferon, and gamma globulin. A transplant nephrectomy was performed on day 4 due to acute rejection and she was started on hemodialysis. The acyclovir dose was decreased at this time. However, 6 days following the start of acyclovir she developed progressively worsening neurological symptoms resulting in a coma on day 8. Fourteen days after acyclovir was begun pre- and post-dose serum concentrations were 7.02 microM and 182.5 microM, respectively. Acyclovir was then discontinued and 2 days later the child's neurological status began to improve. We conclude that acyclovir in children with end-stage renal failure may lead to severe and reversible neurotoxicity, despite acyclovir dosage adjustment based on renal impairment.

Acyclovir↗
PubMed1995

Intramural delivery of agent via a novel drug-delivery sleeve. Histological and functional evaluation.

BACKGROUND: The infusion sleeve is a novel drug-delivery catheter system designed to deliver an agent under controlled conditions into the arterial wall at the site of angioplasty. The purpose of the present study was to characterize the delivery agent via the infusion sleeve in ex vivo and in vivo models. METHODS AND RESULTS: The delivery of horseradish peroxidase via the infusion sleeve was studied in a porcine explanted heart model. Under physiological conditions, arteries underwent balloon injury (approximately 10% overstretch), after which horseradish peroxidase (2.5 mL) was delivered at specific pressures. Cross-sectional analysis demonstrated greater staining when the agent was delivered at increasing pressures. The infusion sleeve was evaluated in an in vivo canine coronary model. With an infusion sleeve loaded over a standard dilatation catheter through a 9F guide, overstretch balloon injury was performed, after which fluoresceinated heparin was delivered. Animals were killed 2 hours after delivery. Fluoresceinated heparin-treated segments demonstrated high fluorescence signals, localizing with smooth muscle cell nuclei with less activity in the interstitium. The functional significance of intramural heparin delivery was studied in a porcine carotid model. In the presence of 111In-labeled platelets, arteries underwent overstretch injury followed by delivery of heparin (50 or 100 units/kg) or vehicle. Platelet deposition was reduced at 30 minutes (57%, P < .01) and 12 hours (39%, P = .06) compared with saline controls. CONCLUSIONS: Agent delivery via the infusion sleeve is pressure dependent; transmural delivery is possible with minimal disruption of arterial wall architecture; the infusion sleeve is compatible with standard angioplasty equipment; and heparin delivery at the site of balloon injury significantly reduces platelet deposition in a porcine model for a minimum of 12 hours.

Angioplasty, Balloon↗
PubMed1994

Epstein-Barr virus surveillance after renal transplantation.

At least 1% of organ transplant recipients develop Epstein-Barr virus-positive, often fatal lymphomas. EBV-positive cells accumulating in some organ transplant recipients were suggested to predict EBV+ lymphoma risk but no prospective study has been reported. We used the polymerase chain reaction (PCR) to detect EBV genomic sequences in successive blood samples of 60 kidney recipients before and up to 11 years after renal transplantation. Xenotransplantation of EBV-positive patient and -negative control samples into mice with severe combined immunodeficiency (SCID) was used to assess the tumor risk inherent in these samples. Despite single EBV+ cell detection sensitivity, none of the control samples was positive for EBV genomic sequences. In nearly 2/3 of patients EBV genomic DNA was detectable 3-6 months after transplantation for about 3 months. No patient developed lymphoma. Lymphocytes from 8 EBV-genome positive patients and 10 healthy donors were engrafted into 38 SCID mice. Human B cell lymphoma developed in 75% of the control grafts within about 3 months. In striking contrast, none of the patient grafts developed lymphoma despite the large numbers of EBV+ cells initially transplanted. Patient lymphocyte grafts were resistant to injection of live EBV, while in control lymphocyte grafts this caused lymphoma development within 3 weeks. We conclude that a 100-1000-fold expansion of circulating EBV+ B cell pools occurs frequently after organ transplantation and that it is balanced by effective EBV immunosurveillant functions resistant to immunosuppression. The mere detection of EBV genomic material was not predictive of lymphoma development.

Adolescent↗
PubMed1993

Importance of platelets in myocardial injury after reperfusion in the presence of residual coronary stenosis in dogs.

Residual coronary stenosis is common after successful thrombolysis for acute infarction. We investigated the role of platelets and the influence of a residual critical stenosis during early reperfusion in survival of reperfused myocardium. The left anterior descending coronary artery was occluded for 90 minutes and reperfused for 6 hours in 5 groups of dogs, 3 with a residual critical stenosis (groups 1 through 3) and 2 without (groups 4 and 5). Thrombocytopenia was produced by an antiserum in groups 2, 3, and 5; group 3 was also made neutropenic by another antiserum. Platelets (groups 1 and 4) and neutrophils (groups 1, 2, 4, and 5) labeled with indium 111 were reinjected at occlusion. Collateral flow was estimated with radioactive microspheres and was statistically similar among groups. Infarct size (percentage of area at risk), revealed by triphenyltetrazolium, was more severe (49.4% +/- 4.0%; p < 0.05) with stenosis (group 1) than without stenosis (group 4: 29.5% +/- 4.6%). Platelet depletion reduced infarct size in group 2 (28.6% +/- 6.3%; p < 0.05 vs group 1) with stenosis, but not in group 5 without stenosis (24.5% +/- 6.2% vs group 4: 29.5% +/- 4.6%). Neutropenia (group 3) did not decrease infarct size in thrombocytopenic dogs. Neutrophil accumulations in reperfused myocardium were similar among groups, but platelets accumulated in greater numbers in reperfused infarcts with stenosis (group 1: 338,581 +/- 52,857/gm; p < 0.05) than without stenosis (group 4: 153,445 +/- 23,949/gm). Therefore a critical stenosis at reperfusion compromises myocardial salvage and increases infarct size by means of a platelet-mediated mechanism.

Animals↗
PubMed1991

Pulmonary thrombo-embolism in the nephrotic syndrome.

The case of a 10.5-year-old boy who had complete right main pulmonary artery thromboembolism complicating steroid-resistant nephrotic syndrome is presented. Despite the massive nature of the lesion clinical symptoms were relatively minor. The thromboembolism was successfully treated with intrapulmonary artery streptokinase. The case highlights the discrepancy that may be found between the clinical and pathological findings in pulmonary thromboembolism in the nephrotic syndrome of childhood.

Child↗
PubMed1991

Post-transplantation outcome of patients with hemolytic-uremic syndrome: update.

The outcome of renal transplantation in patients with hemolytic-uremic syndrome (HUS) is variable in reported cases. An update of the previously published series of patients from the University of Minnesota is reported. Seventeen patients with HUS received a renal transplant. Seven patients had recurrent HUS based on strict clinical and histological features and in 4 of these patients grafts were loss from recurrent HUS, with 1 patient losing three successive grafts. Three patients had histological features consistent with HUS but lacked some of the clinical features. Seven patients had no evidence of recurrent HUS post transplantation. The incidence of recurrence of HUS post transplantation in this updated report remains high (7/17 patients). There was no difference in the allografts used (living-related donor grafts were more common in all groups) or in the immunosuppression in the different groups of patients; only 1 patient with recurrent HUS received cyclosporine. The published cases of transplantation in patients with HUS show a variable recurrence rate of 0-25% in different centers with a poor graft outcome in patients with recurrence; a higher incidence of early chronic vascular rejection with decreased graft survival is also reported in patients without recurrence. Patients with HUS post renal transplant are at a variable risk of recurrence of HUS or decreased graft survival, and the factors responsible for this outcome are not known.

Adolescent↗