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Biomedical subjects

J Dubois

Publications and source records attributed to J Dubois.

At least 19 recordsLinked to original sources
PubMed1999

The kidney in children with tyrosinemia: sonographic, CT and biochemical findings.

BACKGROUND: Tyrosinemia relates to a deficiency of fumarylacetoacetate hydrolase and presents early in life with central nervous system and liver abnormalities. Renal function is often impaired. Little is known about the architecture and function of the kidneys. OBJECTIVE: Imaging changes on US and CT are compared to the function of the kidneys in children with tyrosinemia, and followed after liver transplantation. MATERIALS AND METHODS: Renal sonography, CT and renal function tests in 32 children were reviewed. Renal length, volume, echogenicity and nephrocalcinosis were evaluated. Renal function was assessed by glomerular filtration rate, and the presence of aminoaciduria, acidosis and calciuria. Seventeen children had open renal biopsy during time of liver transplantation. Histology was reviewed. Statistical analyses relating renal structure to function were performed, and repeated after transplantation. RESULTS: The kidneys were enlarged (47 %), hyperechogenic (47 %) and showed nephrocalcinosis (16 %). There was delayed excretion of contrast medium at CT in 64 %. Aminoaciduria was present in 82 % of children, hypercalciuria in 67 %, tubular acidosis in 59 %, and low GFR in 48 %. Delayed excretion of contrast was associated with low GFR (P < 0.05). Renal biopsies showed dilated tubules (81 %), interstitial fibrosis (56 %), glomerulosclerosis (56 %) and tubular atrophy (56 %). During a mean observation period of 3 years following liver transplantation, GFR improved in 50 %, tubular acidosis in 50 % and hypercalciuria in 70 %. No change was noted in renal size or sonographic architecture. CONCLUSION: Renal architecture and function are abnormal in the majority of children with tyrosinemia. Liver transplantation improves renal function in about 50 % of patients, but abnormal renal size and architecture persist.

Amino Acid Metabolism, Inborn Errors↗
PubMed1998

Inhibition of ornithine decarboxylase by ifenprodil.

Ifenprodil (NMDA receptor antagonist) was tested as an inhibitor of ornithine decarboxylase. It was found that ifenprodil inhibited ornithine decarboxylase activity with the same potency as alpha-difluoromethylornithine, a major inhibitor of ornithine decarboxylase. This result suggests that ifenprodil could target either the polyamine site on the NMDA receptor complex or/and polyamine biosynthesis.

Biogenic Polyamines↗
PubMed1998

Incidence and risk factors of catheter-related deep vein thrombosis in a pediatric intensive care unit: a prospective study.

OBJECTIVE: To estimate the incidence and to characterize risk factors for central venous catheter (CVC)-related deep vein thrombosis (DVT) in a pediatric intensive care unit. STUDY DESIGN: Consecutive children admitted to a pediatric intensive care unit who required a CVC for more than 48 hours were examined by Doppler ultrasonography of the catheterized vein at days 2, 4, 6, or 7 after insertion and weekly thereafter until CVC removal. RESULTS: The incidence of CVC-related DVT was 18.3% (17 of 93) (95% confidence interval = 10.2% to 25.8%). Thromboses were diagnosed within the first 4 days of catheter placement for 15 of 17 CVC-related thromboses. Multivariate analysis showed that risk factors most predictive of CVC-related DVT were presence of a cancer (odds ratio = 17.23, 95% confidence interval = 1.5 to 194) and young age (odds ratio for age = 0.72, 95% confidence interval = 0.54 to 0.96). CONCLUSION: The frequency of CVC-related DVT is substantial in pediatric intensive care units. Risk is highest during the 4 days after insertion and decreases thereafter. The clinical impact, optimal prevention, and therapy of these thromboses remain to be determined.

Catheterization, Central Venous↗
PubMed1998

Ability of bisbenzylputrescine and propanediamine analogs to modulate the intracellular polyamine pool of P388D1 cells.

The effects of a series of bisbenzyldiamine analogs have been tested on P388D1 cell line in vitro. Their effects on cell growth, polyamine oxidase (PAO) activity and intracellular polyamine content were determined. The cytotoxicity tests were performed in culture medium supplemented with 100 micromol/L aminoguanidine (I), 100 micromol/L aminoguanidine and 100 micromol/L N,N'-bis(2,3-butadienyl)-1,4-butanediamine (MDL 72,527) (II), and finally 100 micromol/L aminoguanidine and 200 micromol/L D,L-difluoromethylornithine (DFMO) (III). The IC50 values under conditions I and III were similar, suggesting that inhibition of ornithine decarboxylase by DFMO did not affect the biological effect of our derivatives. Spermine and spermidine remained nontoxic in conditions I and III. However in the condition II, the toxicity of all tested compounds (excepted spermidine) was increased, suggesting that the inhibition of cellular PAO increased their toxicity. The enzymatic test of PAO showed that at high doses inhibition of this enzyme by putrescine analogs occurred, while the N-methylated propanediamine derivative increased the enzyme activity; however, these results do not correlate with cytotoxicity tests. When these derivatives were incubated for 48 h with the cells, all of them increased the cell content in putrescine (approximately 160%) and spermine (approximately 145%) and decreased the spermidine content (approximately 75%) without any modification of the total amount of polyamine. The correlation between the cytotoxic results and the intracellular polyamine determination shows that the increase in spermine content along with the inhibition of retroconverting PAO enzyme increases the toxic effect of tested compounds (including spermine), suggesting that spermine toxicity is more important in the absence of intracellular oxidation processes.

Animals↗
PubMed1998

Spleno-caval shunt in children using internal jugular vein graft: a case report.

Several techniques for decompression of portal hypertension have been described. The spleno-caval shunt is an easy and safe technique described in adult patients. However, the procedures described in adults are not adapted to children. We report an adaptation of this technique in a child, using the internal jugular vein as an interposition graft for relief of portal hypertension.

Child, Preschool↗
PubMed1998

Nursery Neurobiologic Risk Score and outcome at 18 months.

The aim of this study was to confirm the predictive value of the nursery Neurobiologic Risk Score. Prospectively, 121 infants (mean birthweight 961 +/- 179 g, gestation 27.0 +/- 1.2 weeks) were followed at 18 months. The nursery Neurobiologic Risk Score was correlated to the developmental quotient (r = -0.54). From low (scores 0-4), to moderate (scores 5-7) to high (scores > or = 8) risk groups, respectively, significant differences were found in mean developmental quotient (101 +/- 9 vs 92 +/- 19 vs 76 +/- 24) and in prevalence of developmental quotients < 90 (12 vs 24 vs 71%), of cerebral palsy (4 vs 19 vs 41%), of severe disabilities (0 vs 24 vs 50%) and of any disability (16 vs 30 vs 71%). Sensitivity, specificity, positive and negative predictive values for any disability were 81, 54, 49 and 84% for a score > or = 5 and 56, 87, 71 and 78% for a score > or = 8. The nursery Neurobiologic Risk Score was useful in predicting 18 months outcome of very premature infants.

Developmental Disabilities↗
PubMed1998

Aneurysmal bone cysts: percutaneous embolization with an alcoholic solution of zein--series of 18 cases.

PURPOSE: To assess the efficacy of percutaneous embolization with an alcoholic solution of zein in the treatment of aneurysmal bone cysts. MATERIALS AND METHODS: Eighteen patients with aneurysmal bone cysts were treated percutaneously with alcoholic zein. The cysts were in the lower limb (n = 7), upper limb (n = 5), pelvis (n = 3), cervical spine (n = 2), and mandible (n = 1). All patients were symptomatic, three had previously undergone surgery. Percutaneous embolization was performed with fluoroscopic or computed tomographic guidance with the patient under general anesthesia. Clinical and imaging follow-up lasted 18 months to 4 years. RESULTS: Percutaneous embolization was performed in 16 cases. In two cases, cystograms showed marked venous drainage and thus embolization was not attempted. Six patients underwent repeat embolization. Complications consisted of a local transitory inflammatory reaction (n = 5), aseptic osteitis (n = 1), and a small pulmonary infarct without sequelae (n = 1). Relief of symptoms was achieved in all patients except one, who underwent surgery. At imaging, improvement was total in 13 cases (87%) and partial in two cases (13%). No recurrence was noted during follow-up. CONCLUSION: Percutaneous embolization of aneurysmal bone cysts with alcoholic zein should be considered a reliable alternative to surgery, especially in cases with a difficult surgical approach or cases of postsurgical recurrence.

Adolescent↗
PubMed1998

Soft-tissue hemangiomas in infants and children: diagnosis using Doppler sonography.

OBJECTIVE: We describe the sonographic appearance and vascularization of hemangiomas and determine if vessel density and peak systolic Doppler shifts distinguish hemangiomas from other superficial soft-tissue masses. SUBJECTS AND METHODS: Our pilot study included 20 infants and children with hemangiomas who were to undergo biopsy before treatment with interferon alpha-2b. We used Doppler sonography to determine the number of vessels per square centimeter, peak arterial Doppler shift, resistive index, and signs of arteriovenous shunting. All hemangiomas showed high vessel density (more than five per square centimeter) and high Doppler shifts (more than 2 kHz), and these two factors became our diagnostic criteria. A prospective study of 116 patients was then carried out. One hundred sixteen consecutive pediatric patients with superficial soft-tissue masses were examined using Doppler sonography; sonographic findings were compared with the final diagnoses that were established by biopsy, CT, or clinical follow-up. RESULTS: The final diagnoses included 70 hemangiomas, 20 venous malformations, three arteriovenous malformations, three arteriolocapillary malformations, and 20 other masses. Fifty-nine lesions showing high vessel density (more than five per square centimeter) and a peak arterial Doppler shift exceeding 2 kHz were correctly diagnosed as hemangiomas (sensitivity, 84%; specificity, 98%). One arteriovenous malformation showed high vessel density and high Doppler shifts, but none of the other masses that were not hemangiomas did. Eleven patients with hemangiomas who were being treated with interferon at the time of the study fulfilled only one of the two diagnostic criteria. CONCLUSION: High vessel density and high peak arterial Doppler shift can be used to distinguish hemangiomas from other soft-tissue masses.

Arteriovenous Malformations↗
PubMed1998

Synthesis and cytotoxicity studies of new analogues of polyamines.

In order to regulate simultaneously the biosynthesis and the transport of natural polyamines, the synthesis of a series of N-methylated analogues of N,N1-Bis(benzyl)-alkanediamines (propanediamine and butanediamine) was achieved and the cytotoxicity of these compounds on the P388D1 cell line was determined. Experiments were conducted in a growth culture medium 20 microM of 2-mercaptoethanol or 0.1 mM of aminoguanidine. Their cytotoxic effects were compared to those obtained under the same conditions with natural polyamines known as toxic compounds at high concentrations. The IC50 of each compound was found very similar for all experimental conditions (IC50 approximately 150 microM) at the opposite of spermidine and spermine which were less toxic (IC50 > 500 microM) when cells were grown in the presence of aminoguanidine (a specific inhibitor of fetal calf serum's PAO). The DL-difluoromethylornithine (DFMO) and MDL 72527DA, two well known inhibitors of ornithine decarboxylase (ODC) and Polyamine Oxidase (PAO) respectively, had no toxicity on the P388D1 cells compared to our compounds. Our most toxic compound was N1,N4-Bis(benzyl)-N1,N4-bis(methyl)-1,4-butanediamine (6) with an IC50 of 127 +/- 3 microM (in culture medium alone). The synthesis of the beta-aminothioether derivative of N-benzylputrescine (11) and the beta-aminothiol derivative of N-benzylspermidine (13) were also related. The Compound 11 was tested against the P388D1 cells, and did not show any cytotoxic effect. The N-methyl derivatives should give the advantage to be used at low concentrations than those used to test the DFMO.

Animals↗
PubMed1998

Modification of paclitaxel metabolism in a cancer patient by induction of cytochrome P450 3A4.

Biliary, plasma, and urinary disposition of paclitaxel and paclitaxel metabolites were determined simultaneously in a patient with percutaneous biliary drain. The complete chemical structures of the major metabolites were established by mass spectrometry and NMR spectroscopy. A nonlinear elimination model was indicated by the fact that the rate of biliary excretion of paclitaxel rose as plasma concentrations fell. Dihydroxypaclitaxel was the predominant biliary metabolite, in contrast to the barely detectable levels in two previous patients. This derivative results from hydroxylation at the C6 position of the taxane ring and at the phenyl C3'-position on the C13 side chain mediated by cytochrome P450 2C8 and 3A4, respectively. In line with this mechanism, the two other main metabolites corresponded to 6alpha-hydroxypaclitaxel and to the paclitaxel derivative hydroxylated in the para-position on the phenyl ring at the C3'-position of the C13. A high CYP3A4 activity in the patient is consistent with the repeated administration of methylprednisolone for 14 days before paclitaxel treatment, a compound known to induce the CYP3A isoform, and with the increased ratio of 6beta-hydroxycortisol/cortisol in urine, an index of CYP3A activity. These findings emphasize the influence of pretreatment with corticoids on the disposition of paclitaxel.

Antineoplastic Agents, Phytogenic↗
PubMed1997

Isocratic high-performance liquid chromatographic method for the separation of isradipine and its main metabolites. Application to in vitro metabolization by h3A4/OR cells.

A reversed-phase HPLC method was developed for the study of isradipine oxidation in vitro. The drug and its main metabolites were determined after extraction from culture media and from h3A4/OR cells having the cytochrome P450 isoenzyme involved in the xenobiotic metabolization. The HPLC assay was fully validated and was used to follow the biotransformation kinetics of isradipine.

Calcium Channel Blockers↗
PubMed1997

Simultaneous determination of cytotoxic (adriamycin, vincristine) and modulator of resistance (verapamil, S 9788) drugs in human cells by high-performance liquid chromatography and ultraviolet detection.

Multidrug resistance (MDR), which was described for structurally and mechanistically unrelated anticancer agents, was modulated in vitro by a series of compounds which were of different chemical origin. In this situation, the selection of a correct assay dosage to study the MDR modulation mechanism was a problem. We developed a high-performance liquid chomatography (HPLC) method which enabled the simultaneous determination of three major cytotoxins (adriamycin, daunorubicin, vincristine) and two well-known modulators (S 9788, verapamil). This assay was fully validated and was used to follow, for the first time, the uptake and accumulation behaviour of adriamycin and S 9788 co-incubated with resistant and sensitive cell lines (KB-3-1; KB-A1).

Antibiotics, Antineoplastic↗
PubMed1997

A practical guide for the diagnosis and treatment of acute sinusitis.

OBJECTIVE: To develop guidelines for the diagnosis and management of acute sinusitis. OPTIONS: Diagnostic clinical criteria and imaging techniques, the role of antimicrobial therapy and duration of treatment, and the role of adjunct therapy, including decongestants, glucocorticosteroids and nasal irrigation. OUTCOMES: Improved accuracy of clinical diagnosis, better utilization of imaging techniques and rational use of antimicrobial therapy. EVIDENCE: A MEDLINE search for relevant articles published from 1980 to 1996 using the MeSH terms "sinusitis," "acute sinusitis," "respiratory infections," "upper respiratory infections," "sinusitis" and "diagnosis," "sinusitis" and "therapy," "sinusitis" and "etiology," and "antimicrobial resistance" and search for additional articles from the reference lists of retrieved articles. Papers referring to chronic sinusitis, sinusitis in compromised patients and documented nonbacterial sinusitis were excluded. The evidence was evaluated by participants at the Canadian Sinusitis Symposium, field in Toronto on April 26-27, 1996. VALUES: A hierarchical evaluation of the strength of evidence modified from the methods of the Canadian Task Force on the Periodic Health Examination was used. Strategies were identified to deal with problems for which no adequate clinical data were available. Recommendations arrived at by consensus of the symposium participants were included. BENEFITS, HARMS AND COSTS: Increased awareness of acute sinusitis, accurate diagnosis and prompt treatment should reduce costs related to unnecessary investigations, time lost from work and complications due to inappropriate treatment. As well, physicians will be better able to decide which patients will not require antimicrobial therapy, thus saving the patient the cost and potential side effects of treatment. RECOMMENDATIONS: Clinical diagnosis can usually be made from the patient's history and findings on physical examination only. Five clinical findings comprising 3 symptoms (maxillary toothache, poor response to decongestants and a history of coloured nasal discharge) and 2 signs (purulent nasal secretion and abnormal transillumination result) are the best predictors of acute bacterial sinusitis (level I evidence). Transillumination is a useful technique in the hands of experienced personnel, but only negative findings are useful (level III evidence). Radiography is not warranted when the likelihood of acute sinusitis is high or low but is useful when the diagnosis is in doubt (level III evidence). First-line therapy should be a 10-day course of amoxicillin (trimethoprim-sulfamethoxazole should be given to patients allergic to penicillin) (level I evidence) and a decongestant (level III evidence). Patients allergic to amoxicillin and those not responding to first-line therapy should be switched to a second-line agent. As well, patients with recurrent episodes of acute sinusitis who have been assessed and found not to have anatomic anomalies may also benefit from second-line therapy (level III evidence). VALIDATION: The recommendations are based on consensus of Canadian and American experts in infectious diseases, microbiology, otolaryngology and family medicine. The guidelines were reviewed independently for the advisory committee by 2 external experts. Previous guidelines did not exist in Canada.

Acute Disease↗
PubMed1997

Placenta percreta: balloon occlusion and embolization of the internal iliac arteries to reduce intraoperative blood losses.

Obstetric hemorrhage is still a potential cause of maternal mortality and morbidity. Angiographic embolization techniques have been described in cases of postcesarean bleeding, vaginal wall hematomas, cervical ectopic pregnancies, and postpartum bleeding to control persistent bleeding from pelvic vessels. We describe two cases of pregnancy complicated with placenta percreta. Balloon occlusion and embolization of the hypogastric arteries were performed during the cesarean section and hysterectomy, resulting in a remarkable reduction in intraoperative blood loss. Balloon occlusion and embolization of the internal iliac arteries significantly reduce intraoperative blood losses.

Adult↗
PubMed1997

Intestinal vascular anomalies in children.

Vascular anomalies are an uncommon cause of gastrointestinal bleeding in childhood. Confusing nomenclature has made objective comparisons of published cases difficult and has interfered with an established consensus regarding diagnosis and therapeutic modalities. The purpose of this study was to clarify the situation by reviewing the records of all children who had intestinal vascular anomalies who were referred to our institution from 1975 to 1995. Thirteen lesions were identified in nine children (five boys and four girls). The median age at clinical onset was 8 years. Only two patients presented with a complex syndrome (Klippel-Trenaunay, 1; Osler-Rendu-Weber, 1). Diagnosis, location, and extension of these anomalies was only possible by angiography, which indicated that seven patients had isolated venous malformations and two had arteriovenous malformations. Because the lesions did not involve the serosa, intraoperative localization was a major problem. The main findings were a few slightly dilated mesenteric veins. Treatment was conservative in four children and surgical in five. Pathological findings on resected bowel demonstrated dilated and abnormal veins in the mucosa and submucosa. Selective angiography should not be delayed in patients with gastrointestinal bleeding if results of all other investigations are negative. Because these lesions are rarely recognizable on operative inspection, precise preoperative angiographic localization of intestinal vascular anomalies is essential to allow for a safe and limited resection of the involved bowel segment. Based on a better understanding of the natural history of these lesions, a classification of vascular anomalies of intestines in children is proposed.

Adolescent↗
PubMed1997

Complete genome sequence of Methanobacterium thermoautotrophicum deltaH: functional analysis and comparative genomics.

The complete 1,751,377-bp sequence of the genome of the thermophilic archaeon Methanobacterium thermoautotrophicum deltaH has been determined by a whole-genome shotgun sequencing approach. A total of 1,855 open reading frames (ORFs) have been identified that appear to encode polypeptides, 844 (46%) of which have been assigned putative functions based on their similarities to database sequences with assigned functions. A total of 514 (28%) of the ORF-encoded polypeptides are related to sequences with unknown functions, and 496 (27%) have little or no homology to sequences in public databases. Comparisons with Eucarya-, Bacteria-, and Archaea-specific databases reveal that 1,013 of the putative gene products (54%) are most similar to polypeptide sequences described previously for other organisms in the domain Archaea. Comparisons with the Methanococcus jannaschii genome data underline the extensive divergence that has occurred between these two methanogens; only 352 (19%) of M. thermoautotrophicum ORFs encode sequences that are >50% identical to M. jannaschii polypeptides, and there is little conservation in the relative locations of orthologous genes. When the M. thermoautotrophicum ORFs are compared to sequences from only the eucaryal and bacterial domains, 786 (42%) are more similar to bacterial sequences and 241 (13%) are more similar to eucaryal sequences. The bacterial domain-like gene products include the majority of those predicted to be involved in cofactor and small molecule biosyntheses, intermediary metabolism, transport, nitrogen fixation, regulatory functions, and interactions with the environment. Most proteins predicted to be involved in DNA metabolism, transcription, and translation are more similar to eucaryal sequences. Gene structure and organization have features that are typical of the Bacteria, including genes that encode polypeptides closely related to eucaryal proteins. There are 24 polypeptides that could form two-component sensor kinase-response regulator systems and homologs of the bacterial Hsp70-response proteins DnaK and DnaJ, which are notably absent in M. jannaschii. DNA replication initiation and chromosome packaging in M. thermoautotrophicum are predicted to have eucaryal features, based on the presence of two Cdc6 homologs and three histones; however, the presence of an ftsZ gene indicates a bacterial type of cell division initiation. The DNA polymerases include an X-family repair type and an unusual archaeal B type formed by two separate polypeptides. The DNA-dependent RNA polymerase (RNAP) subunits A', A", B', B" and H are encoded in a typical archaeal RNAP operon, although a second A' subunit-encoding gene is present at a remote location. There are two rRNA operons, and 39 tRNA genes are dispersed around the genome, although most of these occur in clusters. Three of the tRNA genes have introns, including the tRNAPro (GGG) gene, which contains a second intron at an unprecedented location. There is no selenocysteinyl-tRNA gene nor evidence for classically organized IS elements, prophages, or plasmids. The genome contains one intein and two extended repeats (3.6 and 8.6 kb) that are members of a family with 18 representatives in the M. jannaschii genome.

Anaerobiosis↗
PubMed1997

Peripherally inserted central catheters in infants and children.

PURPOSE: To determine prospectively the feasibility, complications, and mid- and long-term advantages of peripheral insertion of central catheters in infants and children. MATERIALS AND METHODS: During a 15-month period between March 1995 and June 1996, a total of 285 catheter placement attempts were made to peripherally insert central catheters in 183 pediatric patients (89 boys, 94 girls). Phlebographic guidance was used, and the catheters were inserted below the elbow in 99% of cases. Catheter insertion was indicated for prolonged antibiotic therapy in 108 patients (158 catheter placement attempts), hematologic or oncologic care in 24 patients (40 attempts), total parenteral nutrition in 16 patients (46 attempts), and venous access for fluid or blood in 35 patients (41 attempts). The success rate and complications were recorded along with the indication, patient age, and duration of catheter placement. RESULTS: One hundred fifty-two of 158 (96%) catheter placement attempts were successful in outpatients (n = 108), 124 of 127 (98%) in hospitalized patients (n = 75), and 70 of 73 (96%) in patients aged less than 1 year. Infection and pericatheter venous thrombosis were the main complications and were seen in 17 of 276 (6%) and one of 276 (0.3%) catheter placement attempts, respectively. Catheter occlusion occurred in 23 of 276 (8%) catheter placement attempts. CONCLUSION: Peripheral insertion of central catheters was highly feasible in infants and children with this protocol. Such catheters were well tolerated in the pediatric population with a low frequency of complications.

Catheterization, Central Venous↗