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Biomedical subjects

J L Gaillard

Publications and source records attributed to J L Gaillard.

At least 73 records · Page 4Linked to original sources
PubMed1996

Idiopathic disseminated bacillus Calmette-Guérin infection: a French national retrospective study.

OBJECTIVE: Disseminated bacillus Calmette-Guérin (BCG) infection after inoculation of live vaccine is considered to result from impaired immunity of the child. However, in half of the cases, regarded as idiopathic, no well-defined immunodeficiency condition can account for the infection. The objective of the present study is to report the prevalence, clinical features, associated infections, and outcomes of children with idiopathic disseminated BCG infection. DESIGN: National retrospective survey during the period from 1974 through 1994 in France. SETTING: All neonatology and pediatrics units in primary care and referral centers throughout France. PATIENTS: Data were collected from 595 (82%) of 721 units, 377 (93%) of 407 centers, and 320 (93%) of 345 cities. Selection criteria included BCG infection, dissemination to at least two areas beyond the inoculation site, and no well-defined immunodeficiency condition. Sixteen children (8 girls and 8 boys), born to families unrelated to each other but often consanguinous (5 of 16) or abroad (5 of 16). RESULTS: The minimal prevalence rate was estimated at 0.59 cases per 1 million vaccinated children born in France. Clinical features included fever and cachexia, disseminated BCG infection to lymph nodes (15 of 16), skin (13 of 16), soft tissues (11 of 16), lungs (11 of 16), spleen (11 of 16), liver (11 of 16), and bones (9 of 16). Eight children had associated or subsequent severe opportunistic infection (50%), with either nontyphi Salmonella enterica serotypes (7 of 16) or Mycobacterium abscessus (1 of 16). The outcome was poor: 8 children (50%) died; the cause of death was BCG infection for most children (7 of 8); 8 survived until the last follow-up (50%). CONCLUSIONS: Idiopathic disseminated BCG infection is a rare but severe complication of BCG vaccination. The infection probably results from an as yet unknown genetically determined immunodeficiency condition that affects the killing of intracellular bacteria such as BCG and Salmonella.

BCG Vaccine↗
PubMed1995

Prenatal diagnosis of mosaic tetrasomy 12p/trisomy 12p by fluorescent in situ hybridization in amniotic fluid cells: a case report of Pallister-Killian syndrome.

A prenatally detected case of a rare mosaic tetrasomy 12p/trisomy 12p is reported, presenting as the well-known accessory isochromosome 12p and a supernumerary single 12p marker in 17/24 and 6/24 clones of cultured amniotic fluid cells, respectively. The chromosomal nature of both marker chromosomes was investigated in cultured amniotic fluid cells by fluorescent in situ hybridization with various probes: the 12-centromeric probes p alpha 12H8 and D12Z3, a whole chromosome 12 paint, and the chromosome 12p-specific paint M28. DNA analysis revealed a maternal origin of the extra 12p material. After counselling, the parents requested termination of pregnancy. Inspection and autopsy of the fetus revealed many of the dysmorphisms and internal structural abnormalities of the Pallister-Killian syndrome.

Adult↗
PubMed1995

Chronic septic arthritis and osteomyelitis in a prosthetic knee joint due to Clostridium difficile.

A case of chronic septic arthritis and osteomyelitis in a prosthetic knee joint due to Clostridium difficile is reported. A knee prosthesis was installed in a 16-year-old boy for surgical treatment of an osteosarcoma of the femur. Later, the patient suffered a traumatic closed fracture of his patella, and a sterile fluid was aspirated. One month later, the joint displayed inflammation. Culture of the articular fluid yielded a nontoxigenic Clostridium difficile strain. Despite several attempts using conservative medical treatment with penicillins and ornidazole, Clostridium difficile strains with the same antibiotic susceptibility pattern were repeatedly isolated from the joint over an eight-month period. The foreign material was then ablated, and finally, the patient's leg was amputated one year after Clostridium difficile was first isolated. The possible sources of contamination in our case and other reported cases of extraintestinal infection due to Clostridium difficile are discussed.

Adolescent↗
PubMed1995

Correlation between activity of beta-lactam agents in vitro and bacteriological outcome in acute pulmonary exacerbations of cystic fibrosis.

A study was conducted to determine whether a direct relationship exists between beta-lactam and/or aminoglycoside activity measured in vitro and bacteriological outcome in acute pulmonary exacerbations of cystic fibrosis. Twenty-seven patients, aged between 6 months and 24 years (mean age 10 1/2 years), were included in the study and received 41 i.v. courses of a beta-lactam agent combined with an aminoglycoside. A total of 63 Pseudomonas aeruginosa strains were found in sputum taken on admission at densities exceeding 10(6) cfu/g of sputum. For each episode, the serum inhibitory quotient (SIQ) and the serum bactericidal quotient (SBQ) of the beta-lactam agent and of the aminoglycoside administered were determined for the Pseudomonas aeruginosa isolate(s). The SIQs and SBQs were calculated by dividing the average peak serum levels achievable in the patients by the minimal inhibitory concentrations and minimal bactericidal concentrations, respectively. The SIQs and SBQs were compared to bacteriological outcome. Bacteriological success was defined as a decrease of 2 log10 counts or more in the Pseudomonas aeruginosa density in sputum between days 0 and 7 of therapy. The SIQ and SBQ of beta-lactam agents were good predictors of bacteriological outcome: SIQs of < 1:16 were 100% predictive of failure (chi 2 28; p < 0.001) and of > or = 1:64 were 92.9% predictive of success (chi 2 35.68; p < 0.001); SBQs of < 1:8 were 100% predictive of failure (chi 2 42.78; p < 0.001) and of > or = 1:32 were 95.8% predictive of success (chi 2 31.5; p < 0.001). Aminoglycoside SIQs and SBQs were not predictive of outcome.

Adolescent↗
PubMed1995

Cerebrospinal fluid penetration of amikacin in children with community-acquired bacterial meningitis.

The penetration of amikacin into the cerebrospinal fluid (CSF) was studied with 16 children (mean age, 1 year and 9 months; range, 4 months to 8 years) with community-acquired bacterial meningitis. Amikacin was given intravenously at a dose of 7.5 mg/kg of body weight twice daily. CSF was collected on day 1, at the expected peak concentration of amikacin in CSF. The mean (standard deviation) concentration of amikacin in CSF was 1.65 (1.6) mg/liter. Concentrations of amikacin in CSF correlated significantly with CSF glucose levels on admission. The mean concentrations of amikacin in CSF were 2.9, 1.1, and 0.20 mg/liter in patients with CSF glucose levels of < 1, 1 to 2, and > 2 mmol/liter, respectively. Thus, amikacin penetrates the blood-brain barrier substantially in children with bacterial meningitis and achieves particularly high concentrations when CSF glucose level is < 1 mmol/liter on admission.

Amikacin↗
PubMed1995

Immunohistochemical localization of cytochrome P450 aromatase in equine gonads.

Estrogens are the major steroids produced by equine gonads. To identify the cells responsible for estrogen synthesis, an antiserum against purified equine testicular cytochrome P450 aromatase was produced in rabbits. The reactivity and specificity of the antiserum were assessed by ELISA, immunoblot analysis, and immunoneutralization studies. Immunofluorescence microscopy demonstrated that in the male gonad, cytochrome P450 aromatase (P450arom) was localized in the interstitial tissue, whereas, under the experimental conditions used, the Sertoli and germ cells did not show any specific staining. In the ovary, the granulosa cells of small follicles exhibited faint immunofluorescent staining for P450arom and the granulosa cells of large, viable more follicles showed a high degree of immunoreactivity. In the corpus luteum, all the luteinized cells showed immunoreactivity. No immunoreactivity was detected in other cells of small and large viable follicles. Immunolocalization of P450arom in the equine testicular Leydig cells and in ovarian granulosa and luteinized cells indicates that these cells have the ability to metabolize androgens to estrogens and possibly to catechol estrogens.

Animals↗
PubMed1995

In vitro 19-norandrogen synthesis by equine placenta requires the participation of aromatase.

Explants of equine full-term placenta have been shown to synthesize 19-norandrogens from labelled androgens. Steroid metabolites were purified by silica-gel column chromatography then analysed and quantified by c18-reverse-phase HPLC coupled to a radioactive flow detector. 19-Norandrostenedione was subsequently recrystallized to constant specific activity, providing unequivocal evidence of its synthesis by the equine placenta. 19-Norandrostenedione synthesis appeared to be localized in the microsomal fraction. Regardless of the substrate used, formation of 19-norandrogens was far weaker than that of oestrogens; moreover, the yield of 17-oxosteroids produced was much greater than that of 17 beta-hydroxysteroids, suggesting the presence of a dehydrogenase with predominant oxidative activity. Sulphoconjugated steroids formed were less than 0.5% of total steroids. Although 19-nortestosterone could not be generated by equine purified aromatase incubated with labelled testosterone, the synthesis of 19-norandrogens and oestrogens by equine placental explants was blocked by two specific aromatase inhibitors, 4-hydroxyandrostenedione and fadrozole. Our results provide evidence for a placental origin of at least a part of the 19-norandrogens previously identified in the blood of the pregnant mare. Furthermore, it is suggested that 19-norandrogen biosynthesis would involve the enzymatic metabolism of 19-oxygenated androgens formed by equine aromatase.

Androstenedione↗
PubMed1994

Concentrations of ceftriaxone in cerebrospinal fluid of children with meningitis receiving dexamethasone therapy.

The penetration of ceftriaxone into cerebrospinal fluid (CSF) was studied with 11 children (mean age: 2 years, 4 months; range: 4 months to 8 years) with meningitis, receiving dexamethasone (0.15 mg/kg of body weight intravenously four times daily) as adjunctive therapy. Ceftriaxone was given intravenously at doses of 50 mg/kg twice daily to patients < 18 months old and 100 mg/kg once daily to patients > or = 18 months old. CSF was collected after 1 day of treatment at the expected peak concentration of ceftriaxone in CSF. Concentrations of ceftriaxone in CSF ranged from 0.7 to 9.2 mg/liter, with a mean value of 4.0 (standard deviation [SD], 2.9) mg/liter. Values were significantly higher for patients with CSF glucose levels of < 1 mmol/liter on admission to the hospital than for patients with CSF glucose levels of > or = 1 mmol/liter (mean values of 7.1 [SD, 2.2] mg/liter versus 2.2 [SD, 1.1] mg/liter; P < 0.001). After 1 day of treatment, ceftriaxone concentrations in the CSF of children receiving dexamethasone are similar to the mean values reported for children not treated with dexamethasone.

Ceftriaxone↗
PubMed1994

Acute action of choriogonadotropin on Leydig tumor cells: induction of a higher affinity benzodiazepine-binding site related to steroid biosynthesis.

We previously demonstrated that the mitochondrial peripheral-type benzodiazepine receptor (PBR) is coupled to hormone-activated steroidogenesis by regulating the intramitochondrial cholesterol transport, the rate-determining step of steroid biosynthesis. In the present study we examined whether PBR is the site of hormone action using the hCG-responsive MA-10 mouse Leydig tumor cell line as a model system. Within 15 sec of the addition of hCG to Leydig cells a 3-fold cAMP-dependent increase in PBR binding was observed. This rapid increase returned to basal levels within 60 sec. No effect was observed after 1 min in the continued presence of hCG. Scatchard analysis revealed that in addition to the known high affinity (5.0 nM) benzodiazepine-binding site, a second, hormone-induced, higher affinity (0.2 nM) benzodiazepine-binding site appeared. We then examined whether in such a short time frame steroid synthesis occurs. Fifteen-second incubation of MA-10 cells with the inhibitor of cholesterol metabolism aminoglutethimide together with hCG also resulted in an increased rate of pregnenolone formation by their isolated mitochondria that were washed and incubated in aminoglutethimide-free buffer. The dose response of benzodiazepine binding to hCG closely parallels the increase in steroid formation by the mitochondria of stimulated cells. Addition of the selective inhibitor of cAMP-dependent protein kinase, H-89, completely blocked hormone-induced PBR binding and steroid formation, whereas addition of the inactive analog H-85 was without any effect. The addition of flunitrazepam, a benzodiazepine previously shown to inhibit the trophic hormone action on steroidogenesis, completely abolished the hCG-induced rapid stimulation of steroid synthesis. These results demonstrate that in MA-10 cells, the most rapid effect described thus far of hCG and cAMP, is the transient induction of a higher affinity benzodiazepine-binding site, which occurs concomitantly with an increase in the rate of steroid formation. This, in turn, suggests that these hormones alter PBR to activate cholesterol delivery to the inner mitochondrial membrane and subsequent steroid formation.

Animals↗
PubMed1993

An acardiac infant: the extreme form of the twin-twin transfusion syndrome.

A description of the pathologic and clinical findings in a twin with twin-to-twin transfusion syndrome is given. One of them died immediately after birth, with the autopsy revealing the histologic absence of the myocardium. The surviving infant presented with short term heart failure and with persistent left ventricular hypertrophy over 6 months. The circulatory changes in the twin-to-twin transfusion syndrome can result in complete myocardial involution in one and an unexpectedly long compensatory left ventricular hypertrophy in the other infant. Caution is advised in order to avoid misdiagnosing hypertrophic cardiomyopathy. In such a case a longer follow-up period is recommended.

Female↗
PubMed1993

Different in vitro metabolism of 7 alpha-methyl-19-nortestosterone by human and equine aromatases.

The ability of human and equine placental microsomes to aromatize 7 alpha-methyl-19-nortestosterone (MNT) was studied. Kinetic analysis indicates that MNT shares the androgen-binding site of human and equine placental microsomal aromatases. Human placental microsomal estrogen synthetase had about a 2.5-fold higher relative affinity for MNT than the equine placental enzyme (KiMNT/Km androstenedione of 32 versus 87). However, MNT was not metabolized by human placental microsomes, whereas it was very actively metabolized by equine placental microsomes. Further studies using purified equine cytochrome P-450arom indicated that the presence of a 7 alpha-methyl group and the absence of a C19 methyl group did not impair its conversion by the purified enzyme. The product of this reaction was separated and identified as 7 alpha-methylestradiol by gas chromatography coupled to mass spectrometry.

Animals↗
PubMed1993

Bacillus Calmette-Guérin infection after vaccination of human immunodeficiency virus-infected children.

The use of Mycobacterium bovis/Bacillus Calmette-Guérin (BCG) to vaccinate against tuberculosis remains controversial. The development of tuberculosis in human immunodeficiency virus (HIV)-infected children demands specific evaluation of the risk/benefit ratio of BCG vaccination in this situation. In our institution 9 of 68 HIV-infected children vaccinated with BCG before the diagnosis of HIV infection was suspected developed vaccine-related complications: 7 of these children had a large satellite adenopathy with or without skin fistulae, whereas the other 2 had disseminated BCG infection beyond the satellite ganglion (involvement of the spleen and mesenteric and mediastinal lymph nodes in one case and the liver and lungs in the other). The children were vaccinated soon after birth; no particular problems were observed at that time, but complications appeared 3 to 35 months later. All but one of these children had a rapidly progressive form of HIV disease. The possibility of delayed local or disseminated BCG infection must be considered in analysis of the risk/benefit ratio of vaccination of HIV-infected children. The prognosis of HIV infection must be taken into account, even if the child is asymptomatic when vaccination is being considered.

BCG Vaccine↗
PubMed1993

Value of ELISA using antigen 60 for the diagnosis of tuberculosis in children.

We evaluated the possible value of enzyme-linked immunosorbent assay (ELISA) using antigen 60 (A60) for improved diagnosis of tuberculosis in children. Results obtained in 31 children with active tuberculosis and in 16 patients with tuberculous infection without disease were compared with the results of 198 control subjects with no mycobacterial disease. In control children, anti-A60 IgG increased with age and the optical density (OD) in ELISA assays rose from .079 +/- .053 (OD +/- SD) in children younger than 5 years old to 0.146 +/- 0.082 OD in children older than 5 years. In control subjects younger than 2 years old, IgG OD values were significantly higher in BCG-vaccinated children than in nonvaccinated children. At a chosen specificity of 98 percent, a positive serodiagnosis was observed in 68 percent of children with clinically active tuberculosis. In these children with active disease, smears were positive in only 26 percent of cases and mycobacterial cultures yielded the organism in 45 percent of cases. None of the infected children without disease had high IgG OD values. IgM measurements were also evaluated. Mean values from control and diseased children overlapped, leading to a low sensitivity (19 percent) in children with clinically tuberculosis active. We conclude that anti-A60 IgG measurement is a rapid and low-cost technique that enhances the diagnosis of clinically active tuberculosis in children and may distinguish recent infection without disease from infection with disease.

Adolescent↗
PubMed1993

Aromatase activity in the mare ovary during estrous cycle. Measurement of endogenous steroids and of their in vitro inhibitory effect.

This present study was undertaken to clarify estrogen synthesis in the mare ovary. First of all, an evaluation of endogenous steroid contents was carried out in the follicular fluid and in the luteal tissue at different stages of the luteal phase. Radioimmunoassays were performed after separation and purification of each hormone by chromatography. High amounts of conjugated (0.9 mg/l) and unconjugated (4 mg/l) estradiol-17 beta were found in the follicular fluid of the large follicules (50 mm). These concentrations of estrogens decreased drastically in the luteal tissue, and only low levels of circulating estrogens are found during the luteal phase. On the other hand, a high aromatization ability has been evidenced in the cyclic corpus luteum in vitro. In an attempt to clarify the regulation of estrogen synthesis, we have tested the inhibitory effect of several endogenous steroids on equine ovarian aromatase activity. 5 alpha-Dihydrotestosterone appeared to be the most potent competitive inhibitor (Ki = 181 nmol/l) of aromatase activity, while the addition of a 3-sulfate group induced a slump in the inhibitory potency of estrone (Ki = 397 nmol/l vs 2206 nmol/l) and dehydroepiandrosterone (Ki = 291 nmol/l vs 6157 nmol/l). The physiological role of these conjugated steroids has not been known until now; we suggest that they would play a role in protecting aromatase from inhibition, in vivo. The high amounts of progesterone found in the luteal tissue (1.3 g/kg of proteins) might play a role in the regulation of estrogen production either by suppressing the induction of aromatase synthesis or by inhibiting the activity of the enzyme complex.

Animals↗