[Adverse effects and hemodynamic effects of nifedipine as a tocolytic]. / Effets indésirables et effets hémodynamiques de la nifédipine utilisée comme tocolytique.

OBJECTIVES: To describe maternal and fetal adverse effects, in particular cardiorespiratory, of nifedipine as tocolytic, as well as effects on hemodynamic parameters. MATERIALS AND METHODS: A retrospective evaluative study describing the use of nifedipine as tocolytic at CHU Sainte-Justine in Montreal. Demographic data as well as maternal blood pressure and adverse effects, and maternal and fetal heart rate were collected from medical records of women treated with nifedipine following our tocolysis protocol between January 1st 2004 and March 1st 2007. RESULTS: The medical records of 213 pregnant women were included in the study. Cardiorespiratory adverse effects were noted in 69 (32.4%); of these, 19 (8.9%) had serious cardiorespiratory adverse events, including 6 acute pulmonary edema or overload. Mean maternal systolic and diastolic blood pressures were significantly decreased and mean maternal and fetal heart rates were significantly increased after the bolus dose. Other adverse effects were reported for 100 (46.9%) women. CONCLUSION: Nifedipine may cause cardiorespiratory adverse effects warranting a close monitoring.

Plotting transcutaneous bilirubin measurements on specific transcutaneous nomogram results in better prediction of significant hyperbilirubinemia in healthy term and near-term newborns: a pilot study.

BACKGROUND: The American Academy of Pediatrics has recommended a systematic assessment before discharge for the risk of severe hyperbilirubinemia. Plotting total serum bilirubin (TSB) or transcutaneous bilirubin (TcB) on a TSB hour-specific nomogram is proposed as a tool for laboratory evaluation. OBJECTIVES: The aim of this study was to compare the predictive characteristics, particularly the incidence of false negative rate (FNR), of the practice of plotting TcB values on the TSB hour-specific risk nomogram versus on transcutaneous nomogram. METHODS: Paired TSB and TcB measurements were conducted on 141 newborns. Risk of developing significant hyperbilirubinemia was defined as infants with bilirubin level ≥ 75% on TSB or ≥ 95% on TcB nomogram. TSB values, plotted on the TSB nomogram of Bhutani et al. [Pediatrics 1999;103:6-14], were used as reference. TcB values were plotted on the TSB nomogram and on the transcutaneous nomograms of Maisels and Kring [Pediatrics 2006;117:1169-1173] and Fouzas et al. [Pediatrics 2010;125:e52-e57]. RESULTS: Plotting TcB measurements on a TSB nomogram resulted in a trend towards a higher FNR when compared to Maisels' and Fouzas' nomograms (18.0/1,000 compared to 10.2/1,000 and 8.6/1,000 respectively). Although not statistically significant, plotting TcB on transcutaneous nomogram resulted in better predictive values with the Fouzas' nomogram, having the best sensitivity (90.0%) and specificity (87.79%) as well as the highest positive (35.97%) and negative (99.14%) predictive value. CONCLUSION: Plotting TcB on a TSB nomogram may result in increased rate of FNR and decreased predictive characteristics. The practice of plotting TcB on a TSB nomogram needs further evaluation.

[How to become a good pediatrician: a balance between theoretical and clinical training]. / Cómo llegar a ser un buen pediatra: un equilibrio entre la formación teórica y la formación clínica.

We review a different way of teaching medicine and pediatrics which balances theory and clinical training for undergraduate, postgraduate and during continuing education. We also discuss the role of the teacher. We recommend better evaluation of students and teacher assessments. We discuss the discrepancies and the harmonization of all Institutions involved in pediatric education. We analyze the model of teaching medicine and pediatrics in the Province of Quebec, Canada. We introduce advices on the application of skills in a pediatrics training program.

[Acute rheumatic fever: 27 year experience from the Montreal's pediatric tertiary care centers]. / Fiebre reumática aguda: 27 años de experiencia en los hospitales pediátricos en Montreal.

OBJECTIVES: To examine the epidemiology, clinical characteristics and outcomes in a cohort of children with acute rheumatic fever (RF) over the past 27 years in Montreal. METHODS: The medical records of patients younger than 18 years of age hospitalized and diagnosed with RF in Montreal between January 1979 and December 2005 were reviewed. RESULTS: Among the initial 134 charts selected, 36 children were already followed-up for chronic RF and the remaining 98 patients (51 % females) who fulfilled the Jones criteria for acute RF were included in the analysis. The mean age at diagnosis was 10.1 +/- 3.0 years (range: 3-17). Over the 27-year study period, there was a mean incidence of 3.6 patients/year without peaks, but onset occurred in the last 15 years in almost two-thirds of the patients. Forty-nine percent of the patients were Canadian-born non-aboriginal (CbnA) and the remaining patients were Canadian-born aboriginal (CbA) or foreign-born (Fb). Carditis was diagnosed in 73 % of the patients and Sydenham's chorea in 49 %. Of the CbnA children, 39 % had carditis compared with 61 % of children from other ethnic groups (P = 0.003). However, the form of presentation was chorea in 69 % of CbnA children vs. 31 % of children from other ethnic groups (P < 0.001). No deaths were attributable to acute RF although 2 % of the patients relapsed during the study period. Severe cardiac sequelae requiring valve replacements occurred in 6.1 %. CONCLUSION: The incidence of acute RF in Montreal was low but consistent over the 27-year study period. Clinical presentation varied depending on ethnicity.

[Evaluation of transcutaneous bilirubin measurement and agreement with bilirubinemia]. / Evaluation de la mesure transcutanée de la bilirubine et concordance avec la mesure sur sang total et plasma.

Evaluation of the neonates for jaundice and kernicterus is indispensable when early hospital discharge has become standard practice. Transcutaneous bilirubin (TcB) measurement is an advantageous option because of its non-invasive nature and the possibility of its use near the patient. The point of care device BiliCheck has been compared in numerous instances to serum bilirubin. However, its clinical utility remains a subject of discussion. We have compared total blood bilirubin (TBB) concentrations to TcB values using the BiliCheck in newborns at 48 +/- 12 hours of life, at the time of discharge when they have lost weight. One hundred and ninety-six term neonates were initially included into the study. Transcutaneous bilirubin could be compared to whole blood bilirubin for 178 of them. Methods were compared by linear regression analysis and by the non-parametric Bland and Altman method. The correlation between BiliCheck and whole blood bilirubin was adequate (r(2): 0.7768). However, the Bland-Altman analysis revealed a 95% CI of -50.4 to 47.5 micromol/L. Transcutaneous bilirubin was also compared to a measure on plasma in a sub-group of 53 infants, the correlation was 0.7749 with a 95% CI of -35.8 to 46.5 micromol/L. Comparing total blood bilirubin with plasma bilirubin in 35 patients, we observed a similar results with a correlation of 0.7583 and a 95% CI of -34.6 to 40.7 micromol/L. Finally, the extent of weight loss observed in our group of patients had little influence and did not affect the agreement between the 2 approaches. We conclude that the BiliCheck may be used to monitor bilirubin in term neonates at 48 hours of life even with a weight loss. Clinicians have however to be conscious of the limit of the precision of the measures both for the BiliCheck and the laboratory methods.

Natremia of healthy term newborns at 48 h of life: influence of feeding patterns.

OBJECTIVES: To describe natremia in healthy term newborns and determine whether there is a relationship between blood sodium and feeding patterns. METHODS: All normal newborns, admitted to the nursery between January and March 2004 were eligible for this prospective cohort study. Inclusion criteria were: > or =37 weeks of gestational age, birth weight > or =2500 g, Apgar scores > or =7 at 5 and 10 min and normal physical examination. A capillary blood sample was taken at 48+/-12 h of life. RESULTS: Blood samples from 126 newborns were analyzed. Mean gestational age was 39.6 weeks, birth weight was 3414 g and weight loss at 48 h of life was 6.5% of birth weight. Mean capillary blood sodium was 141 mmol/L (SD 3.4). Exclusively, breast-fed newborns had statistically higher mean blood sodium (141 mmol/L, SD 3.0) than the non-exclusively breast-fed+formula fed group (139 mmol /L, SD 3.7). There was a significant linear association between blood sodium and the quantity of milk supplements received as well as between blood sodium and weight loss. CONCLUSIONS: Most newborns have blood sodium values within a narrower range than previously described in the literature. We also demonstrate that the exclusively breast-fed infants appear to have marginally but statistically higher values of blood sodium than non-exclusively breast-fed and formula-fed infants.

[New trends in pediatric endocarditis]. / Nuevas tendencias de la endocarditis pediátrica.

OBJECTIVES: To evaluate the epidemiology, etiology and outcome of endocarditis in a cohort of pediatric patients and to compare the main characteristics with our previous experience. MATERIAL AND METHODS: Patients aged less than 18 years of age diagnosed with endocarditis at the Sainte-Justine Hospital, University of Montreal between 1-1986 and 12-2000 were studied. The recent case series was compared with our previous experience from 1960-1985. RESULTS: Fifty-six children with endocarditis were included in the 1986-2000 series: 35 children with congenital heart disease, 15 with serious underlying disease and six healthy children. The mean age was 7 years and 10 months. Fifty-four percent of the patients were boys. The incidence of endocarditis increased from 1.5 cases/year in the 1986-2000 series to 4 cases/year in the 1986-2000 series. In the 1986-2000 series, 10 (17.9 %) patients had a central catheter. Sixteen (28.6 %) patients had a vascular prosthesis. Blood cultures were positive in 50 patients (89 %): Streptococci were found in 48 % of the patients and Staphylococci in 34 %. Echocardiography was positive in 36 of 55 patients (65.4 %). All children were treated with intravenous antibiotics for a mean of 43 +/- 15 days. There were no recurrences. Significant morbidity developed in 26 patients (46 %). Embolic phenomena were seen in 11 children (20 %). Twelve patients (21 %) needed surgery. Of the six healthy children, five developed complications. Overall, seven children (12.5 %) died; all were older than 6 years of age. Comparing our experience from 1960-1985 with that from 1986-2000 revealed that morbidity decreased from 85.7 % to 46.4 % and mortality decreased from 27 % to 12.5 %. CONCLUSIONS: Physicians must recognize that children with underlying immunodeficiency and those with central catheters have an increased risk of endocarditis. Healthy children with endocarditis have a greater risk of complications. Morbidity and mortality due to endocarditis has diminished considerably in recent years.

Immunohistochemical screening for beta6-integrin subunit expression in adenocarcinomas using a novel monoclonal antibody reveals strong up-regulation in pancreatic ductal adenocarcinomas in vivo and in vitro.

AIMS: To analyse the expression of alphavbeta6, an epithelial integrin involved in wound healing and tumorigenesis, in various human carcinoma types. METHODS AND RESULTS: A new monoclonal antibody to the human beta6 subunit, 5C4, was used to locate alphavbeta6 in 157 cancers of gastroenteropancreatic and 21 of lung origin. The data were validated by analysis of alphavbeta6 extracted from histological sections. Alphavbeta6 integrin showed strongest expression in 34 pancreatic ductal adenocarcinomas (mean score 2.88 +/- 0.52), followed by 24 intestinal-type gastric carcinomas (1.45 +/- 1.06) and eight lung adenocarcinomas (1.37 +/- 1.1). Moderate expression was found in 31 diffuse-type gastric carcinomas (0.94 +/- 0.83), seven duodenal adenocarcinomas (0.8 +/- 1.34) and 26 colorectal adenocarcinomas (0.76 +/- 0.71). Little alphavbeta6 was seen in seven liver cell carcinomas and six neuroendocrine tumours. Well-differentiated carcinomas expressed more beta6 than poorly differentiated tumours. Peritumoral epithelial tissues where alphavbeta6-expressing tumours arose also expressed alphavbeta6. There was no correlation between expression of alphavbeta6 and its ligands tenascin and fibronectin in pancreatic and gastric carcinomas. Spheroid formation by pancreatic carcinoma cell lines led to alphavbeta6 up-regulation, but appeared independent of classical ligand binding to alphavbeta6. CONCLUSIONS: Our findings indicate that: (i) alphavbeta6 is overexpressed in pancreatic adenocarcinomas; (ii) alphavbeta6-positive carcinomas originate from alphavbeta6-expressing tissues; (iii) alphavbeta6 expression in tumours seems to be regulated independently from that of its ligands tenascin and fibronectin; and (iv) in-vitro overexpression of alphavbeta6 in pancreatic carcinoma cell lines accompanies spheroid formation.

Corneal disease in patients with chronic renal insufficiency undergoing hemodialysis.

PURPOSE: To evaluate alterations of the corneal endothelium in patients undergoing hemodialysis for renal insufficiency. METHODS: Sixty-six patients undergoing hemodialysis received a complete ophthalmologic examination. The state of the endothelium was assessed using pachymetry and specular microscopy. The group of patients undergoing dialysis was divided according to the time of dialysis, aluminum, product of calcium and phosphate in blood, and parathyroid hormone to analyze the influence of these factors. The possible presence of iron and aluminum in the aqueous humor of patients who underwent and those who did not undergo hemodialysis was also estimated. RESULTS: Patients undergoing hemodialysis did not have significant corneal edema. Cell density was significantly lower in patients undergoing dialysis than in patients not undergoing dialysis; this reduction appeared to be associated with length of dialysis and was unrelated to serum aluminum and calcium levels. Patients undergoing dialysis did not have cell polymorphism or polymegethism, although there was a tendency toward increased polymegethism with length of dialysis. Aluminum and iron were not increased in the aqueous humor of patients undergoing dialysis. CONCLUSIONS: The alteration of the endothelium that we found is not related to the elements studied. It is possibly the result of another product dissolved in the anterior chamber or to the alterations of the anterior segment that these patients are known to have.

Surgical resection and chemotherapy improve survival rate for patients with hepatoblastoma.

BACKGROUND: The authors reviewed retrospectively their experience in 30 children with hepatoblastoma (HB). Despite an increased trend in the incidence of HB during the last 2 decades, an encouraging cure rate has been achieved with complete resection of the tumor and chemotherapy before or after surgery with cisplatin plus doxorubicin (Adriamycin) or cisplatin plus vincristine plus 5-Fluorouracil. RESULTS: There were 10 female and 20 male patients. For the period from 1963 to 1980 there were 8 patients, and for the period from 1981 to 1998 there were 22 patients. Their mean age at surgery was 16 months (range, 3.5 months to 5.5 years). Tumors were localized to the right lobe in 10 (42%), to the left lobe in 7 (29%), and in both lobes in 7 (29%) of the resected patients. Tumors were greater than 10 cm in size in 16 (67%) of these patients. Twenty-four patients (80%), underwent liver resection before or after chemotherapy. One patient (3%) with an unresectable tumor received chemotherapy and a liver transplant. In 5 patients (17%) the hepatic involvement was too extensive for resection. The types of resection performed were right lobectomy in 7, left lobectomy in 6, right trisegmentectomy in 8, left trisegmentectomy in 2, and middle hepatectomy in 1. The overall survival rate for 35 years of the study was 60% (18 of 30). With the association of surgery and chemotherapy (1981 through 1998) survival rate is 82% (14 of 17). Overall median follow-up in our study is 8 years (range, 2.5 to 24 years). CONCLUSIONS: There has been a dramatic improvement in the results of treatment of hepatoblastoma. Formerly, only 25% to 30% of patients were cured, whereas today, with combination of chemotherapy and surgery, 75% to 80% may be cured.

Kidney androgen-regulated protein interacts with cyclophilin B and reduces cyclosporine A-mediated toxicity in proximal tubule cells.

The gene for kidney androgen-regulated protein (KAP) is the most abundant and specific gene expressed in mouse kidney proximal tubule cells, where it is tightly regulated by steroid and thyroid hormones in different tubule segments. Despite the cell-specific expression, strict regulatory mechanisms, and relative abundance, nothing is known of the function of its encoded protein, which does not exhibit known structural or functional domains, or homologies with other sequences in the data bases. We raised monoclonal antibodies against KAP, which specifically recognize a protein with an apparent molecular mass of 20 kDa in crude kidney homogenates, the distribution and regulation of which parallel that of its mRNA. To gain insight into its function, we performed a yeast two hybrid screen and determined that KAP specifically interacts with cyclophilin B. Furthermore, cyclosporine A (CsA)-treated mice exhibited a significant decrease in KAP levels, and tetracycline-controlled overexpression of KAP in stably transfected proximal tubule cells significantly decreased the toxic effects of CsA. Taken together, these results indicate a functional relationship among KAP-, cyclophilin B-, and CsA-mediated nephrotoxicity and suggest an important role of KAP in renal physiology, providing new data on the molecular mechanisms implied in the toxic effects of CsA.

Regulation of ionotropic glutamate receptor subunits in different rat brain areas by a preferential sigma(1) receptor ligand and potential atypical antipsychotic.

The effect of chronic administration of the putative atypical antipsychotic E-5842, a preferential sigma(1) receptor ligand, on ionotropic glutamate receptor subunit levels of mRNA and protein, was studied. The repeated administration of E-5842 differentially regulated levels of the NMDA-2A and of GluR2 subunits in a regionally specific way. Levels of immunoreactivity for the NMDA-2A subunit were up-regulated in the medial prefrontal cortex, the frontoparietal cortex, the cingulate cortex, and in the dorsal striatum, while they were down-regulated in the nucleus accumbens. Levels of the GluR2 subunit of the AMPA receptor were up-regulated in the medial prefrontal cortex and the nucleus accumbens and down-regulation was observed in the dorso-lateral striatum. Regulation of the levels of mRNA for the different subunits was also observed in some cases. The results show that E-5842, through a mechanism still unknown, is able to modify levels of several glutamate receptor subunits and these changes could be related to its antipsychotic activity in pre-clinical tests.

Changes in phosphoinositide signalling activity and levels of the alpha subunit of G(q/11) protein in rat brain induced by E-5842, a sigma(1) receptor ligand and potential atypical antipsychotic.

Changes in the phosphoinositide (PPI) signal transduction system induced by E-5842, a new sigma(1) (sigma(1)) receptor ligand and potential atypical antipsychotic, were studied in the rat frontal cortex, hippocampus and striatum. Acute treatment with E-5842 increased phospholipase C (PLC) activity in the striatum and the hippocampus. Chronic treatment with E-5842 induced an increase in the activity of PLC in the frontal cortex and the striatum. Similar up-regulation of the activity of the enzyme was also observed in rat frontal cortex membranes in presence of GTPgammaS. After chronic treatment with E-5842, it was also observed a significant increase of the immunoreactivity levels of G(q/11)alpha in the frontal cortex. Our results suggest that part of the antipsychotic effects of E-5842 could be related to the regulation of the PPI signal transduction pathway, especially after a prolonged treatment.

Repair of the huge umbilical hernia in black children.

Surgical repair of large umbilical hernias may present a challenging surgical problem. The currently described surgical techniques often yield disappointing results. The authors describe a new technique that allows for the repair of the fascial defect and the creation, with the use of a square cutaneous flap, of a neoumbilicus with sufficient depth and a good cosmetic appearance.

Past and future of biliary atresia.

BACKGROUND: With the advent of liver transplantation the outcome of children with biliary atresia (BA) has improved. Is Kasai hepatic portoenterostomy (KHPE) still a valuable option for the treatment of these patients? METHODS: From 1974 to 1998, 77 patients with biliary atresia have been treated at our institution: 50 girls and 27 boys. RESULTS: Seventy-four patients had a KHPE, and 3 patients had no KHPE because of delay in diagnosis. A total of 65 of 74 patients (88%) had undergone KHPE type I, 4 patients (5.4%) KHPE type II, 3 patients (4%) had a Suruga modification, and 2 patients (2.6%) had a portocholecystostomy. Among the 74 patients, 11 were lost to follow-up and their cases were considered failures. Seventeen of our patients are alive at long-term follow-up after KHPE. Among the 77 patients, 33 (43%) had an orthotopic liver transplantation (OLT). Successful KHPE patients underwent transplant at a mean age of 9 years, and KHPE failed at a mean age of 11 months. A total of 25 of 77 (32%) of patients are alive thanks to OLT. In the cohort, the overall survival rate for the KHPE plus OLT is 42 of 77 (55%). Mortality and morbidity rates were more frequent among the younger patients who had early OLT after KHPE failure. In our series, overall survival rate was improved when the patient had a successful KHPE (P < .001). CONCLUSIONS: Kasai hepatic portoenterostomy (KHPE) continues to be a valuable procedure in the treatment of infants with biliary atresia (BA). Successful KHPE permits transplantation at an age at which mortality and morbidity are decreased leading to a better outcome.

[In vitro resistance to fluconazole and itraconazole in clinical isolates of Candida spp and Cryptococcus neoformans]. / Resistencia in vitro al fluconazol e itraconazol en aislamientos clínicos de Candida spp y Cryptococcus neoformans.

An in vitro susceptibility testing of 181 strains of six species of Candida and 21 strains of Cryptococcus neoformans was carried out in order to investigate the resistance to new antifungal drugs. We have studied clinical isolates from 200 different patients of Hospital del Mar (Barcelona) and Hospital La Inmaculada (Almería). An agar diffusion method (NeoSensitabs, Rosco, Taastrup, Denmark), was employed with fluconazole, itraconazole, and reference drugs amphotericin B, flucytosine, tioconazole and ketoconazole. A high level of susceptibility was found for amphotericin B in C. neoformans strains while 19% of them were resistant to flucytosine. All the strains of C. neoformans and Candida guilliermondii were susceptible to the new azoles derivatives and also Candida parapsilosis and Candida albicans had a great susceptibility to this antifungals. A greater level of resistance was found for Candida krusei, Candida tropicalis and Candida glabrata to fluconazole, itraconazole and ketoconazole, but resistance to fluconazole and itraconazole is not always linked because ten resistant strains for fluconazole were susceptible to itraconazole, and two other resistant to itraconazole were susceptible to fluconazole.

Candiduria in non-neutropenic critically-ill surgical patients. Detection of IgA, IgG and IgM antibodies to Candida albicans by germ tube immunofluorescence.

The significance of indirect immunofluorescence using Candida albicans germ tube as well as blastospore antigens in the diagnosis of isolated candiduria in non-neutropenic, critically-ill surgical patients was assessed. Ten patients with isolated candiduria, 12 with systemic candidosis and 10 with multifocal muco-cutaneous candidosis were included in the study. The sera of another 10 critically-ill patients with no signs of candidosis served as controls. The patients' sera were tested for IgG, IgA and IgM antibodies. The results obtained confirmed that indirect germ tube immunofluorescence is a useful procedure for differentiating systemic candidosis from colonisation of the urinary tract. Indirect immunofluorescence with blastospores, although more sensitive than germ tube immunofluorescence, cannot distinguish muco-cutaneous candidosis from systemic candidosis. Therefore, indirect germ tube immunofluorescence is regarded a useful complementary test to evaluate candiduria in non-neutropenic, HIV-negative, critically ill patients.