Can we predict 22q11 status of fetuses with tetralogy of Fallot?

OBJECTIVE: To determine if chromosome 22q11 deletion status can be predicted in fetuses with tetralogy of Fallot as regards additional phenotypic anomalies. METHODS: One hundred and fifty-one consecutive fetuses with tetralogy of Fallot without or with pulmonary atresia were screened for 22q11 deletion. Additional echographic features [increased nuchal translucency (NT), intrauterine growth retardation (IUGR), polyhydramnios, extracardiac malformations, pulmonary arteries abnormalities] were noted. RESULTS: Twenty-five fetuses had a 22q11 deletion (16.6%). Increased NT, polyhydramnios and IUGR were more frequent in fetuses with 22q11 deletion as well as pulmonary arterial abnormalities. When these different features were present in the same fetus with tetralogy of Fallot, 22q11 deletion can be predicted with a sensitivity of 88%. CONCLUSION: Simple echographic features can help to predict 22q11 status in fetuses with tetralogy of Fallot. This may improve the efficiency of prenatal screening for this defect.     

Perinatal management and outcome of prenatally diagnosed congenital diaphragmatic hernia: a 1995-2000 series in Rennes University Hospital

OBJECTIVES: To assess the prognosis of prenatally diagnosed congenital diaphragmatic hernia (CDH) during the years 1995-2000 in order to improve prenatal counselling. METHODS: Retrospective study of all 31 cases of women with prenatally diagnosed CDH. RESULTS: Nine pregnancies (29%) were terminated and two fetuses (6%) were stillborn. Ten fetuses (32%) had associated anomalies (four Fryns' syndrome) and four (13%) had underlying chromosomal anomalies. Twenty pregnancies were continued. Seven babies died before surgery either immediately in the delivery room (five between 1 and 45 min), or during the 'stabilisation period' (two babies, 7 and 21 h). Three babies presented with trisomy 18, Fryns' syndrome or transposition of the great arteries with microdeletion 22q11. Thirteen babies had the defect repaired (median 18 h, range 4-72 h) and 12 survived. Mechanical ventilation was required for a median of 12 days. One survivor has cerebral palsy. CONCLUSION: Of 31 prenatally diagnosed CDH cases 38% are alive, of 20 ongoing pregnancies 60% are alive, and of 13 babies who underwent surgery 92% are alive. No baby with associated malformations survived. These numbers need to be known by each member of the counselling team in order to give parents adequate information to make their decision.     

Sonohysterography: a prospective survey of results and complications in 81 patients

PURPOSE: To evaluate the sonohysterography (SHG) for the diagnosis of intrauterine abnormalities and describe complications and failure rate. STUDY DESIGN: A prospective survey on 81 patients, (44 patients with menometrorrhagia, 30 with postmenopausal bleeding and 7 with infertility) was conducted. Histopathology and clinical survey, if sonohysterography was normal, were the gold standards. RESULTS: Pathology has been performed in 55 cases. There were four failures (cervical stenosis), one severe complication (endometritis), one pelvic pain. Sensitivity and specificity of sonography were 56 and 83%; for sonohysterography 88 and 98%; and for hysteroscopy 78 and 97%. Sonohysterography was accurate for the diagnosis of the submucous myoma component. CONCLUSION: Sonohysterography is available in uterine pathology, easy, safe and cheap, but sonographists and patients should be informed of the little risks of such examination technique.     

Congenital dyserythropoietic anemia,type 1, in a polynesian patient: response to interferon alpha2b

The authors attempted to assess the utility of interferon alpha2b treatment in a Polynesian girl with a relatively severe form of congenital dyserythropoietic anemia, type 1. The diagnosis was established using routine hematologic and biochemical tests, light and electron microscopy, and electrophoresis of red cell membrane proteins. Response to the treatment was monitored using the blood count and reticulocyte count. The patient was age 14 when interferon treatment was started. Previously, she had been partially dependent on transfusions, and gallstones and iron overload had developed. The dose of interferon alpha2b was initially 3 x 10 units three times a week for 1 year and 3 x 10 units twice a week thereafter. On this treatment, hemoglobin and reticulocytes increased and transfusions became unnecessary. In keeping with a few previous reports, interferon alpha2b proved to be effective in congenital dyserythropoietic anemia, type 1. The patient became transfusion-independent. More cases need to be studied to optimize the dosage of interferon alpha2b and determine how long the treatment can be tolerated.     

Promoters P3, Pa/Pb,P4, and P5 upstream from bla(TEM) genes and their relationship to beta-lactam resistance

Using an isogenic system, we have determined the impact that the four promoters known to control bla(TEM) gene expression have on beta-lactamase activity. For both TEM-1 and TEM-30, this activity gradually increased in relation to the presence of promoters P3, Pa/Pb, and P4 upstream of the corresponding gene. Promoter P5, only found upstream of the bla(TEM-1B) gene, was related to the highest expression of this gene.     

Identifying quality outliers in a large,multiple-institution database by using customized versions of the Simplified Acute Physiology Score II and the Mortality Probability Model II0

OBJECTIVE: To assess whether customized versions of the Simplified Acute Physiology Score (SAPS) II and the Mortality Probability Model (MPM) II0 agree on the identity of intensive care unit quality outliers within a multiple-center database. DESIGN: Retrospective database analysis. SETTING AND PATIENTS: Patient subset of the Project IMPACT database consisting of 39,617 adult patients admitted to surgical, medical, and mixed surgical-medical intensive care units at 54 hospitals between 1995 and 1999 who met inclusion criteria for SAPS II and MPM II0. INTERVENTIONS: Customized versions of SAPS II and MPM II0 were obtained by fitting new logistic regressions to the data by using the risk score as the independent variable and outcome at hospital discharge as the dependent variable. The data set was divided randomly into a training set and a validation set. Each model was customized by using the training set; model performance was then assessed in the validation set by using the area under the receiver operating characteristic curve and the Hosmer-Lemeshow statistic. The final models were based on the entire data set. The level of agreement between the customized models on the identity of quality outliers was evaluated by using kappa analysis. MEASUREMENTS AND MAIN RESULTS: Both customized models exhibited good discrimination and good calibration in this database. The area under the receiver operating characteristic curve was 0.83 for MPM II0 and 0.872 for SAPS II following model customization. The Hosmer-Lemeshow statistic was 12.3 ( >.14) for MPM II0, and 8.17 (p >.42) for SAPS II, after customization. Kappa analysis showed only fair agreement between the two customized models with regard to the identity of the quality outliers: kappa = 0.44 (95% confidence interval, 0.24, 0.65). CONCLUSIONS: Customization of SAPS II and MPM II0 to the Project IMPACT database resulted in well-calibrated models. Despite this, the models exhibited only a moderate level of agreement in which hospitals were designated as quality outliers. Seventeen of the 54 hospitals were categorized differently depending on which of the two scoring systems was used. Therefore, the rating of quality of care appears, in part, to be a function of the prediction model used.     

Mechanisms of membrane potential sensing with second-harmonic generation microscopy

We characterize the transmembrane voltage response of a novel second-harmonic generation (SHG) marker using a screening protocol with giant unilamellar vesicles. Two mechanisms are found to contribute to the voltage response: (1) an electro-optic-induced alteration of the molecular hyperpolarizability and (2) an electric-field-induced alteration of the degree of molecular alignment. We quantify the relative weights and of these contributions and provide an upper limit to their response time, which is found to be submillisecond. The identification of two voltage response mechanisms leads to new strategies for the molecular design of membrane potential markers.     

In vivo selection of a chromosomally encoded beta-lactamase variant conferring ceftazidime resistance in Klebsiella oxytoca

Klebsiella oxytoca clinical isolate A was recovered from the urine of a 55-year-old man with prostatic and urinary tract infections. This isolate displayed a beta-lactam resistance phenotype consistent with overproduction of a chromosomally encoded class A beta-lactamase and had decreased susceptibilities to all beta-lactams except ceftazidime, cephamycins, and carbapenems. Four weeks after treatment with an antibiotic regimen that included ceftazidime, K. oxytoca isolate B, which had a high level of resistance to ceftazidime, was isolated from the urine of the same patient. Isoelectric focusing analysis of the culture extracts of these isolates gave a pI of 5.4 for both isolates. Cloning experiments with the PCR products of the bla(OXY) gene resulted in two Escherichia coli DH10B recombinant clones with resistance phenotypes mirroring those of the parental isolates. Sequencing analysis revealed that the bla(OXY-2-5) gene from K. oxytoca B had a single nucleotide substitution compared to the sequence of the bla(OXY-2) gene from K. oxytoca A, leading to a proline-to-serine substitution at position 167, according to the numbering of Ambler. Biochemical analysis of purified OXY-2-5 showed that it had the ability to hydrolyze ceftazidime. This is the first report of in vivo selection of a K. oxytoca isolate that produced a chromosomally encoded beta-lactamase conferring resistance to ceftazidime.