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Biomedical subjects

J L Gaillard

Publications and source records attributed to J L Gaillard.

At least 91 records · Page 5Linked to original sources

Serum bactericidal test as a prognostic indicator in acute pulmonary exacerbations of cystic fibrosis.

The serum bactericidal test has been used for many years for optimal assessment of the efficacy of antibiotic therapy in patients with infective endocarditis and other bacterial infections. Its capacity to predict the bacteriological outcome of acute pulmonary exacerbations in patients with cystic fibrosis was evaluated. A total of 54 courses of intravenous antibiotic therapy were analyzed in 22 patients, whose ages ranged from 4 months to 24 years (mean age: 10 years). The serum bactericidal activity of blood samples, taken at expected peak and trough antibiotic levels on day 4 of therapy, were determined against the potentially pathogenic strains isolated in sputum at the time of admission. For 104 isolates (64 Pseudomonas aeruginosa, 28 Staphylococcus aureus, and 12 Haemophilus influenzae strains), the peak and trough bactericidal titers were compared to bacteriological outcome. Bacteriological success was defined as a decrease of 2 log10 units or more in the bacterial density in sputum between days 0 and 7 of therapy. At peak antibiotic levels, serum bactericidal titers of 1:128 or more were 96% (all isolates) and 89% (P aeruginosa isolates), predictive of cure, whereas serum bactericidal titers of less than 1:16 were 100% predictive of failure for all infecting bacteria. In patients aged less than 18 years, the best peak titer for predicting success was 1:64, with a predictive value of 96% for titers of 1:64 or greater. The peak titer that best predicted success in patients aged 18 years or more was 1:128, with a predictive value of only 83% for titers of 1:128 or greater.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

Prenatal diagnosis of Klippel-Trenaunay-Weber syndrome: a case report.

At 20 weeks of gestation, a typical combination of a massive enlargement of the right fetal leg and multiple cystic lesions was detected at ultrasound examination. Color-coded Doppler examination revealed no arteriovenous fistulae. These findings allowed an in utero diagnosis of the Klippel-Trenaunay-Weber syndrome, which was confirmed after subsequent termination of the pregnancy. The severe malformation involved the upper and lower right leg. No arteriovenous fistulae were found.

Journal Article↗

Maternal serum alpha-fetoprotein levels and fetal outcome in early second-trimester oligohydramnios.

Early second-trimester oligohydramnios was associated with normal maternal serum alpha-fetoprotein (MSAFP) levels in nine out of 26 cases (35 per cent). Congenital malformations of the fetal urinary tract resulting in fetal anuria were present in nine cases; in seven of them, normal MSAFP levels were measured. In contrast, normal MSAFP levels were established in only 2 out of the 17 cases without fetal malformations. These data suggest that fetal urine is the major source of elevated AFP in the maternal compartment in early second-trimester oligohydramnios. This is further supported by the lack of any relationship between concentrations of MSAFP non-reactive with Concanavalin A, originating mainly from the yolk sac-derived amniotic fluid AFP pool, and the presence of fetal diuresis. Three out of 26 women had experienced early second-trimester oligohydramnios in a previous pregnancy, suggesting the existence of a recurrence risk for this condition.

Concanavalin A↗

Pulmonary vascular abnormalities in experimentally induced congenital diaphragmatic hernia in rats.

In infants with congenital diaphragmatic hernia (CDH), abnormalities of the pulmonary arteries are present consisting of increased medial wall thickness and decreased external diameter. This forms the morphological substrate for persistent pulmonary hypertension, one of the leading causes of the high mortality in these patients. To elucidate the significance of these abnormalities, experimental models are required that mimic as close as possible the human situation. In our rat model we are able to study the hypoplastic CDH lungs extensively. In this study we performed a histological evaluation of the pulmonary arterial bed in the control group and the nitrofen-treated group in which the latter was divided into two subgroups, CDH and normal diaphragm. We examined the newborn rats after perfusion of the pulmonary arteries with barium gelatine and subsequent fixation. At the level of the respiratory bronchioles significant differences in the vessels were found consisting of decreased external diameter and increased wall thickness as percentage of the external thickness in CDH lungs compared with controls. Abnormal muscularization of the peripheral branches of the CDH pulmonary arteries was also found. We concluded that the rat model strongly resembles the human situation concerning the arterial bed in the lungs.

Animals↗

Binding of estrogen-3-sulfates to stallion plasma and equine serum albumin.

The binding of estrone-3-sulfate (E1-3-S) and estradiol-3-sulfate (E2-3-S) to adult stallion plasma was determined and compared with the binding to equine serum albumin (ESA). On the ESA molecule, two binding sites for E1-3-S with an association constant of 1.3 x 10(5) M-1 and several sites of weaker affinity were found; the data for E2-3-S showed the existence of four binding sites of moderate affinity (1 x 10(5) M-1) and several sites of weaker affinity. The removal of albumin from the stallion plasma resulted in the absence of binding of E1-3-S or E2-3-S, whereas the removal of glycoproteins resulted in binding parameters similar to those obtained with whole plasma. These results indicate that ESA is the only estrogen sulfate binder in horse plasma. Under physiological conditions, 95% of E1-3-S was bound to ESA.

Animals↗

Reduced virulence of a Listeria monocytogenes phospholipase-deficient mutant obtained by transposon insertion into the zinc metalloprotease gene.

A phospholipase-deficient mutant, termed JL762, was obtained from a virulent strain of Listeria monocytogenes by screening a bank of 5,000 Tn1545 transposon-induced mutants on 2.5% egg yolk brain heart infusion agar. As previously shown (J. Mengaud, C. Geoffroy, and P. Cossart, Infect. Immun. 59:1043-1049, 1991), the transposon insertion took place inside the gene mpl, which encodes a zinc metalloprotease. By Western blot (immunoblot) analysis, we showed that loss of phospholipase activity was associated with loss of a 29-kDa zinc-dependent phosphatidylcholine-phospholipase C (PC-PLC) in culture supernatant of JL762 and of EGD-SmR incubated with ion chelator. As the parental strain, JL762 still produced in supernatants approximately 33-kDa proteins antigenically closely related to the 29-kDa PC-PLC. These results strongly suggest that the zinc metalloprotease of L. monocytogenes might play a role in the maturation of the 29-kDa PC-PLC. Although the uptake and the intracellular growth of bacteria were not affected in vitro, we found that the virulence of mutant JL762 was strongly impaired in the mouse.

Animals↗

Entry of L. monocytogenes into cells is mediated by internalin, a repeat protein reminiscent of surface antigens from gram-positive cocci.

We report the identification of a previously unknown gene, inlA, which is necessary for the gram-positive intracellular pathogen Listeria monocytogenes to invade cultured epithelial cells. The inlA region was localized by transposon mutagenesis, cloned, and sequenced. inlA was introduced into Listeria innocua and shown to confer on this normally noninvasive species the ability to enter cells. Sequencing of inlA predicts an 80 kd protein, internalin. Two-thirds of internalin is made up of two regions of repeats, region A and region B, and the C-terminus of the molecule is similar to that of surface proteins from gram-positive cocci. Internalin has a high content of threonine and serine residues, and the repeat motif of region A has regularly spaced leucine residues. As evidenced by Southern blot analysis, inlA is part of a gene family. One of them is the gene situated directly downstream of inlA, called inlB, which also encodes a leucine-rich repeat protein.

Amino Acid Sequence↗

Equine testicular aromatase: substrates specificity and kinetic characteristics.

1. In the stallion, estrogens were synthesized and sulfated in vivo by the testis. 2. The equine testicular enzyme aromatized androgens and 19-norandrogens with similar velocity, but not 16 alpha-hydroxytestosterone or epitestosterone in contrast to the human placental aromatase. 3. One single enzyme was implicated in the aromatization of androstenedione, testosterone, 19-norandrostenedione and 19-nortestosterone by ETMES. 4. During the process of androstenedione aromatization by ETMES, 19-hydroxyandrostenedione and 19-oxoandrostenedione were released and 4-hydroxyandrostenedione was a competitive inhibitor causing an additional irreversible enzyme inactivation which is what occurs with HPMES. 5. Dihydrotestosterone was a potent competitive inhibitor of aromatase activity.

Androgens↗

Outbreak of gut colonization by Pseudomonas aeruginosa in immunocompromised children undergoing total digestive decontamination: analysis by pulsed-field electrophoresis.

We analyzed an outbreak of gut colonization by Pseudomonas aeruginosa occurring in an intensive care hematology unit by using conventional typing methods and pulsed-field electrophoresis. In October and November 1989, the feces of four immunocompromised children undergoing total digestive decontamination were colonized by P. aeruginosa. Ten isolates were obtained from the gut flora in pure culture. Retrospective investigations found that one P. aeruginosa isolate from stools of one of the patients was already present at high counts 6 months before the outbreak. This patient had been discharged from the unit in May 1989 and had been readmitted concomitantly with the outbreak. Only pulsed-field electrophoresis could demonstrate that a single epidemic strain was present in the fecal flora of the children. This strain had probably been brought into the unit by the patient with chronic fecal carriage.

Anti-Bacterial Agents↗

Detection of anti-listeriolysin O for serodiagnosis of human listeriosis.

To see whether detection of antibodies against listeriolysin O (LLO) could be used to diagnose human listeriosis, sera from 28 patients infected with Listeria monocytogenes and 101 controls were tested by dot-blot titration with purified LLO. 27 patients (96.4%) with listeriosis produced specific anti-LLO. Anti-LLO was detected in 8 (15.6%) of 51 healthy controls and in 6 (12.0%) of 50 controls who had various bacterial, fungal, and viral infections. Anti-LLO titres did not exceed 100 in these two control groups. Anti-LLO could be detected soon after clinical onset of listeriosis, and antibodies persisted for at least several months. This test might be useful for epidemiological surveys and for serodiagnosis of listeriosis, especially when bacteria cannot be isolated.

Adolescent↗

Estrogen synthetase in the horse. Comparison of equine placental and rat liver NADPH-cytrochrome c (P-450) reductase activities.

NADPH-cytochrome c (P-450) reductases from horse placenta and rat liver were purified and their biological activities compared using cytochrome c as substrate. Rat liver reductase was purified to electrophoretic homogeneity in one chromatographic step on 2',5'-ADP agarose, and had a relative mass of 85,000 Da as estimated by SDS-PAGE. Equine placental reductase was separated from cytochrome P-450 on aminohexyl-Sepharose 4B and further purified on 2',5-ADP agarose; this preparation exhibited two bands, one of 85,000 and one of 80,000 Da, on SDS-PAGE. The lower molecular weight form was assumed to be a proteolytic product of the higher molecular weight form. A high retention of activity was obtained in both preparations. Equine placenta and rat liver enzymes were found to exhibit very similar Vmax and Km, suggesting that they are not species specific.

Animals↗

Pulmonary hypoplasia secondary to oligohydramnios with very premature rupture of fetal membranes.

Over a 3-year-period, pulmonary hypoplasia was diagnosed in 14 cases out of a group of 150 infants born prematurely after prolonged rupture of fetal membranes and prolonged amniotic fluid leakage of whom 30 died. Review of these patients revealed pulmonary hypoplasia to be the main single cause of neonatal death (13/30). In contrast to literature data, infection was only a minor complication in this series. Lung hypoplasia was clearly correlated with long-standing rupture of membranes with oligohydramnios. It is concluded that upon premature rupture of fetal membranes, prenatal care should focus on oligohydramnios, because if this condition is prolonged, the risk of pulmonary hypoplasia increases accordingly.

Amniotic Fluid↗

Experimentally induced congenital diaphragmatic hernia in rats.

Experiments to induce congenital diaphragmatic hernia (CDH) in rats, by means of administering a single dose of 2,4-dichlorophenyl-P-nitrophenyl (Nitrofen) on the 10th day of gestation, are reported here. Previously, congenital diaphragmatic hernia has been induced in sheep late in fetal development, and in mice early in gestation. The rat model, including a control group, was used to evaluate lung development and the presence of lung hypoplasia by morphometrical analysis. It was found that the single dose of Nitrofen, given 5 days before the normal closure of the diaphragm in the rat, leads to a high incidence of diaphragmatic hernia, mainly on the right side, and highly abnormal lung development (hypoplasia) comparable to the human situation. Both the lung weight/body weight index as well as the radial alveolar count were significantly lower in animals with CDH (P less than .05). This animal model offers a good opportunity to study abnormal lung development in relation to ventilatory capacity and pulmonary vascular reactivity.

Animals↗

Catheter related sepsis during long-term parenteral nutrition in paediatric gastroenterology patients: a study of 185 consecutive central venous catheters.

We report the results of a prospective study of catheter-related sepsis (CRS) in 154 gastroenterology paediatric patients treated for medical (n = 102) or surgical (n = 52) disorders. Over 2 years, 185 central venous catheters (CVC) were placed, including 155 Broviac and 30 Jonathan Shaw CVC. CVC remained in place 13,331 days (6,539 days of cyclic parenteral nutrition), with a mean catheter life of 72 days. Forty-eight episodes of CRS occurred, most of them due to coagulase-negative staphylococci (n = 29) and Staphylococcus aureus (n = 17). CRS rate was 0.26, with an overall incidence of 1 infection per 278 days of parenteral nutrition (PN). Factors significantly associated with CRS were: age 1-5 years (p < 0.01), a medical indication for treatment (p < 0.001) and summer months of PN (p < 0.01). Interestingly, CRS occurred predominantly (65%) within the first 2 months following CVC placement and the risk of infection correlated with local haemorrhage at the time of insertion (p < 0.01). Appropriate systemic therapy, without removing the catheter, permitted resolution of 90.9% (40/44) of all CRS and 100% (28/28) of CRS due to coagulase-negative staphylococci.

Journal Article↗

[Comparison of the pharmacokinetics of etomidate in children and in adults].

Etomidate pharmacokinetics were compared in 12 children (P group) (age 7 to 13 years, weight 22 to 48 kg) and in 4 adult women (A group) (age 28 to 52 years, weight 46 to 72 kg), A.S.A. 1, undergoing minor non abdominal surgery. They were unpremedicated and anaesthetized with alfentanil 100 micrograms.kg-1, and isoflurane 2 vol % in N2O/O2 (1/1). Etomidate was administered as a bolus: 0.3 mg.kg-1 in adults and 0.4 mg.kg-1 in children. Venous plasma samples were frozen until further etomidate assay with a HPLC technique. In all patients but two children, data were fitted to a three rather than a two compartment model. Differences between groups (mean +/- SD values) included Vdc (P: 0.66 +/- 0.31 l.kg-1; A: 0.27 +/- 0.15 l.kg-1; p less than 0.01), t1/2 pi (P: 5.4 +/- 2.9 min; A: 2.7 +/- 5.7 min; p less than 0.05) and plasma clearance (P: 17.2 +/- 4.6 ml.kg-1.min-1; A: 10.9 +/- 3.3 ml.kg-1.min-1; p less than 0.05). No statistical difference was found between A and P groups for the following parameters: t1/2 alpha (37.1 +/- 12.0 min vs 26.8 + 15.1 min), t1/2 beta (260 +/- 99 min vs 175 +/- 99 min), Vdss (2.5 +/- 1.11.kg-1 vs 2.8 +/- 1.61.kg-1), Vd beta (4.1 +/- 2.41.kg-1 vs 4.0 +/- 2.21.kg-1), and MRT (228 +/- 80 min vs 172 +/- 101 min). No age-related difference was found inside P group with regard to pharmacokinetic parameters. In conclusion, a 30% higher etomidate bolus dosage is required in children than in adults to achieve similar plasma concentrations, due to a higher volume of the initial compartment. In comparison to adults the higher clearance suggests higher maintenance dose requirements in children.

Adult↗

Analgesia for appendectomy: comparison of fentanyl and alfentanil in children.

During etomidate-N2O vecuronium anaesthesia for appendectomy, three groups of 13 children received fentanyl as a 10 micrograms.kg-1 loading dose and 2 micrograms.kg-1 increments in Group F, alfentanil as a 100 micrograms.kg-1 initial loading dose and either 20 micrograms.kg-1 increments in Group AB or 1 microgram.kg-1.min-1 continuous infusion in Group AI. On the basis of intraoperative heart rate changes, the opioid regimen was less efficient in Group AB (P less than 0.05). Based upon equianalgesic cumulative dosage, the alfentanil/fentanyl potency ratio was in the range of 1/10 to 1/13. The awakening time was similar in all groups, as were the duration of postoperative analgesia, the incidence of postoperative pain and the incidence of nausea and vomiting. We conclude that high-dose alfentanil is as efficient as fentanyl for intra and postoperative analgesia in children undergoing appendectomy.

Alfentanil↗