PubMed Health⌕ Search

Biomedical subjects

R Gilly

Publications and source records attributed to R Gilly.

At least 19 recordsLinked to original sources
PubMed1996

[Aerosol administration of a replication defective recombinant adenovirus expressing normal human cDNA-CFTR in the respiratory tractus in patients with cystic fibrosis].

At present it is conceivable to think that gene therapy represents a way to treat or even prevent the respiratory manifestations of cystic fibrosis. Consistent to such a concept, there is sufficient evidence that Ad-CFTR, a recombinant replication-deficient adenovirus expressing the human cystic fibrosis transmembrane conductance regulator cDNA, can vectorize the expression of a functional CFTR (cystic fibrosis transmembrane conductance regulator) to the nasal and airway epithelia. The clinical protocol was designed to assess the safety of single escalating doses of a replication defective adenovirus expressing the cystic fibrosis transmembrane conductance regulator gene (Ad-CFTR) when administered to the tracheobronchial portion of the airways and whether biological efficacy of CFTR delivery could be demonstrated. Six cystic fibrosis patients received nasal instillation and subsequent aerosol (Optineb, Air Liquide, Paris, France) administration of Ad-CFTR the following day. Doses (pfu) applied to the nose were 10(5) (patients SG and PB), 10(7) (patients FP and EP) and 4 x 10(8) (patients DS and FG), while aerosolised doses were 10(7) (patients SG and PB), 10(8) (patients FP and EP) and 5.4 x 10(8) (patients DS and FG), respectively. No acute toxic effects, no increase in the titer of anti-adenovirus antibodies and no spreading or shedding of Ad-CFTR were detected. In one patient Ad-CFTR DNA was found in the urine and blood two days after aerosolisation. Ad-CFTR DNA was detected in nasal and bronchial brush samples, in BAL, in saliva and tonsils 21, 8, 14 and 4 days post virus administration, respectively. Ad-CFTR mRNA (RT-PCR on bronchial cells) and CFTR protein (immunochemistry on nasal and bronchial cells) were detected up to 14 days following Ad-CFTR administration. These results show that the nebulisation of Ad-CFTR is a possible approach for treating the respiratory manifestation of cystic fibrosis.

Adenoviridae↗
PubMed1995

Regional distribution of substance P binding sites in the brainstem of the human newborn.

The distribution of [3H]substance P ([3H]SP) binding sites in the brainstem of the human newborn was investigated in eleven cases (aged 1 h to 6 months) by in vitro quantitative receptor autoradiography. The binding of [3H]SP to newborn brainstem tissue was found to be saturable (for the eight cases examined, Kd and Bmax (M +/- S.E.M.) were 0.29 +/- 0.03 nM and 206 +/- 21 fmol/mg tissue, respectively). Competition studies showed unlabeled SP to be the most potent peptide for displacing [3H]SP binding from tissue sections. The desaturating effect of GTP on the specific binding of [3H]SP was also investigated, but was not found to be significant. Autoradiographic analysis showed that the neurokinin-1 (NK-1)/SP binding sites were widely but unevenly distributed, and that they varied with age. The highest densities of (NK-1)/SP binding sites were observed in the locus coeruleus, olivaris inferior nuclei, raphe magnus and obscurus nuclei, while low to moderate densities were observed in other brainstem structures. These findings support the idea that SP is involved in cardiovascular regulation, and that it may interact with the catecholaminergic and/or serotonergic system.

Autoradiography↗
PubMed1995

Diagnostic criteria for cystic fibrosis in men with congenital absence of the vas deferens.

The high frequency of cystic fibrosis (CF) mutations in males with absence of vas deferens supported the hypothesis of a primarily genital phenotype of CF disease. To consider the idea of an attenuated form of CF, we investigated 14 men with congenital bilateral aplasia of the vasa deferentia. All patients were consulting for infertility and none was known to have CF. The median age was 30.5 years (range, 20-38 yr). DNA analysis for 22 CF mutations showed at least 1 mutation in 10 patients (71%), whereas the CF carrier frequency is only 4% in the general population. Three compound heterozygotes were identified, all carriers of the R117H mutation. The sweat test was considered positive in 6 patients (43%), and a high frequency of radiologic evidence of sinus disease (8 patients) and of elevated antibodies to Pseudomonas (8 patients) was found. Only 2 patients were free of all these criteria for CF disease. This study strengthens the hypothesis that absence of vas deferens is an attenuated form of CF. We propose a combination of tests including DNA study, computerized tomographic scan of the paranasal sinuses, and testing of anti-Pseudomonas antibodies when the sweat test is inconclusive.

Adult↗
PubMed1994

[Destombes-Rosai-Dorfman syndrome: 2 uncommon clinical forms].

Two cases of Destombes Rosai Dorfman's syndrome are presented. Diagnosis was performed by superficial lymph node biopsy. The first case concerned a nine and half years old girl with cervical adenopathy who developed a compressive mediastinal adenopathy responsible for a right lower lobe atelectasis. Because of local lung suppuration a lobectomy had to be performed. The second case concerned a fourteen years old boy with recurrent fever, diffuse superficial lymph nodes and erythematous skin rash. The two patients showed clinical and biological inflammatory symptoms without any immunodeficiency. No aetiological agent could be identified. Antibiotics and corticoids had no effect but the two patients recovered (after 18 months follow up in case 2). These two particular cases confirm the clinical course heterogeneicity of the syndrome which requires histological diagnosis.

Adolescent↗
PubMed1994

Mutation analysis in 600 French cystic fibrosis patients.

The cystic fibrosis transmembrane conductance regulator (CFTR) gene of 600 unrelated cystic fibrosis (CF) patients living in France (excluding Brittany) was screened for 105 different mutations. This analysis resulted in the identification of 86% of the CF alleles and complete genotyping of 76% of the patients. The most frequent mutations in this population after delta F508 (69% of the CF chromosomes) are G542X (3.3%), N1303K (1.8%), W1282X (1.5%), 1717-1G-->A (1.3%), 2184delA + 2183 A-->G (0.9%), and R553X (0.8%).

Alleles↗
PubMed1994

Studies of neuroregulators in the brain stem of SIDS.

Some dysmaturity of neuroregulator neuronal systems may be responsible for brain stem disorders. These disorders may partly explain the mechanism of death in SIDS. The available data using microbiochemical assays, immunocytochemical techniques and autoradiographic methods seem to show anomalies of some monoaminergic and of some peptidergic systems, especially in the medulla oblongata. All these data need to be confirmed by further studies. It should be understood that one positive effect of such neuroanatomical study on SIDS is to gain 'normative' data on the human brain during development.

Brain Stem↗
PubMed1993

[Is male infertility caused by congenital bilateral atrophy of the vas deferens a clinical form of mucoviscidosis?].

We investigated clinical data, sweat electrolytes and cystic fibrosis (CF) mutations in twelve patients with congenital bilateral aplasia of vasa deferentia (CBAVD) to debate arguments for diagnosing CF. Sweat chloride concentration was definitely raised in four patients. Three patients are CF compound heterozygotes. Six patients are CF heterozygotes. This result reinforces the hypothesis that white males with CBAVD might have a mild form of CE.

Atrophy↗
PubMed1993

Absence of adrenergic neurons in nucleus tractus solitarius in sudden infant death syndrome.

Immunohistochemical study of catecholamine synthesizing enzymes tyrosine hydroxylase (TH) and phenylethanolamine-N-methyl transferase (PNMT) was performed in lower brain stem of 5 controls and 9 sudden infant death "syndrome" (SIDS) cases. No difference was noticed in TH immunoreactive neuronal groups. With anti-PNMT antibody, electively in nucleus gelatinosus (NG), a subnucleus of nucleus tractus solitarius, an absence of immunoreactivity was noticed. Catecholamine neuronal cell bodies in NG were present. The discussion favours a nonartefactual interpretation of data. A delay in maturation would be a possible explanation.

Brain Stem↗
PubMed1993

[Serodiagnosis of Pseudomonas aeruginosa infections in mucoviscidosis: comparative study of Western blotting, ELISA exotoxin A and ELISA phospholipase C].

Anti-Pseudomonas aeruginosa antibodies were studied by Western Blot, ELISA-exotoxin A and ELISA-phospholipase C for 91 serums from 31 patients with cystic fibrosis. More, for the two enzyme-linked immunosorbent assays, 44 serums from 44 healthy individuals were studied as controls. The study of these three parameters revealed the followings: with no infection by Pseudomonas aeruginosa all the results were negative, at the beginning of the infection, anti-exotoxin A antibodies appeared in first, followed in some cases by the reactions of Western Blot, anti-phospholipase C antibodies became positive at last and went on a par with the installation of the chronic characteristic of the infection, as soon as the chronicity were indisputable, the three methods revealed elevated serum antibodies amounts. Generally there was a correlation between detected antibodies and Pseudomonas aeruginosa isolation in sputum. Among these three methods, ELISA-exotoxin A appeared to be the most interesting because of its good reproducibility and its early positivity, before the others methods and sometimes before Pseudomonas aeruginosa isolation. It would be a significant argument to establish as soon as possible an antimicrobial therapy.

ADP Ribose Transferases↗
PubMed1992

MRI in Sturge-Weber syndrome.

Five children (3 girls, 2 boys, aged from 1 to 18 years) presenting with Sturge-Weber syndrome were explored by MRI with contrast injection in 2 cases. The respective positions of CT and MRI are discussed: CT is the method of choice to display leptomeningeal calcifications. MRI seems to be more accurate than CT to determine the location of the lesions and to demonstrate the enhancement of the angioma after contrast injection.

Adolescent↗
PubMed1991

[Aberrant left pulmonary artery and tracheal abnormality].

A case of left pulmonary artery sling and tracheobronchial tree malformation is reported in a 3 month-old infant. Acute respiratory presenting symptoms required mechanical ventilatory support. The malformation was suspected because of ventilatory support difficulties. Barium oesophagogram showed an anterior indentation, fiberoptic bronchoscopy and tracheobronchography showed a severe tracheal stenosis from a right bronchus lobaris superior to the carina. This was worsened by the right side compression of trachea end part, due to the abnormal left pulmonary artery as demonstrated by pulmonary angiography. A surgical left artery transposition relieved lateral compression and allowed weaning of ventilatory support. After a 27 month-follow-up, the girl's respiratory status is satisfactory.

Female↗
PubMed1990

[Cystic fibrosis: choices of treatment of respiratory manifestations (except Pseudomonas aeruginosa infections)].

A knowledge of the natural history of cystic fibrosis is the basis for a treatment which, so far, has only been symptomatic. The three fundamental elements of our therapeutic possibilities are: prevention and treatment of bronchial obstruction, administration of antibiotics active against staphylococci and Haemophilus influenza (Pseudomonas aeruginosa infections will be dealt with in another article of this journal), and control of bronchial inflammatory processes. Some complications of cystic fibrosis regarded as serious are no longer beyond our resources. Many works of fundamental research are needed, concerning the local conditions that are necessary to the selective implantation and the development of Staphylococcus aureus in the lung, and the virus Staphylococcus and Staphylococcus-Pseudomonas relations. The real hope of an absolute treatment justifies the new, aggressive therapeutic approach but the precise indications of an antistaphylococcal treatment must still be evaluated carefully. Finally, the complexity of a treatment which must constantly be adjusted is one of the reasons for the existence of "specialized consultations", the organization of which is summarized.

Airway Obstruction↗
PubMed1990

[Antibiotic therapy in cystic fibrosis: uncertainty and reality].

Antibiotics inspite of certain contradictions remain an important part of the treatment of mucoviscidosis (MCV). Despite this the current practice of their extensive use does not always rest on firmly placed criteria. Before colonisation with pseudomonas (PA), the systemic prophylaxis of infection by Staphylococcus (SA), or Hemophilus (HI) is debatable. At the time of exacerbations, even if this may be caused by a virus, the prescription of antibiotics (ATB) active against SA and HI should often be continued for 2 or 3 weeks to maintain a durable clinical benefit. While awaiting the results of complimentary multi-centre trials at present underway it remains uncertain whether eradication of the germ at all costs remains indispensable. Systemic anti-PA antibiotic therapy given quarterly from the time of the implantation of the germ has not yet proved to have definitive advantages when compared to the treatment of exacerbations. An appreciation of the benefit of therapy should take count not only of survival curves but also of the quality of life. The indications for treatment should not neglect the possibility of therapeutic progress, sometimes unexpected. Intensive therapy may be justifiable in certain cases awaiting a lung transplant. ATB is only one part of treatment aimed strictly at the broncho-pulmonary system. Drainage and account of infectious agents other than classical bacterial infections or pathogenic mechanisms other than infections (nutritional problems, bronchial hyper-reactivity, immunological phenomenon, or primary or secondary inflammatory changes) should not be ignored.

Anti-Bacterial Agents↗
PubMed1990

[Pregnancy and cystic fibrosis. A case history].

The authors report a case of pregnancy in a patient suffering from moderately severe cystic fibrosis (the syndrome consisted of diffused obstruction in respiratory function with a vital capacity of 79% and the lowered blood oxygen level with arterial blood gas estimations; oxygen saturation was 94%). The condition was marked by temporary worsening during the pregnancy in which infective bronchitis supervened). She also threatened to go into early labour and did in fact deliver at 36 1/2 weeks of an infant which was normal for the duration of the maturity. The authors review previous known facts about cystic fibrosis. A study of the literature has made it possible to be more accurate in describing methods of ante natal diagnosis of the condition and ways of following the pregnancy and the illness as well as the woman's fertility and her ability to breast feed.

Cystic Fibrosis↗