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Biomedical subjects

D Hubert

Publications and source records attributed to D Hubert.

At least 55 records · Page 3Linked to original sources
PubMed1995

Three novel sequence variations in the 5' upstream region of the cystic fibrosis transmembrane conductance regulator (CFTR) gene: two polymorphisms and one putative molecular defect.

More than 400 sequence alterations have been identified in the whole coding sequence of the cystic fibrosis transmembrane conductance regulator (CFTR) gene corresponding to the 27 exons and their exon-intron boundaries. However, in some CF chromosomes, no mutation has yet been detected. In such cases, we have explored the promoter and the sequence up to position -1000 from the cap site, by using denaturing gradient gel electrophoresis. This study concerning 35 CF chromosomes has allowed us to identify three novel sequence variations located in the 5' upstream region of the gene. The T to G substitution located at position -895 from the cap site could be considered as a polymorphic variation. The second substitution (C to T at position -816) has been detected on only one CF chromosome, but does not concern a regulatory DNA element previously described. Conversely, the third substitution (a T to G substitution at position -741 from the cap site) is located at a potential AP-1 binding site. We have investigated, by electrophoretic mobility shift assay, the ability of this region to bind nuclear factors. We have found that the normal sequence between -740/-745 does not bind either the AP-1 transcription factor or AP-1 related proteins, and that the T to G-741 mutated sequence exhibits an abnormal binding pattern suggesting the possible deleterious effect of still unknown negative trans-acting factors.

Base Sequence↗
PubMed1995

Variation in air medical outcomes by crew composition: a two-year follow-up.

STUDY OBJECTIVE: In a previous 1-year retrospective study, we found no differences in outcomes of patients transported by physician/nurse (P/N) and nurse/nurse (N/N) air medical crews. To confirm this finding and to identify any trends in outcome that might be associated with changes in crew composition, we prospectively collected and analyzed 2 additional years of severity and outcome data. DESIGN: Prospective cohort. SETTING: University hospital-based air medical program. RESULTS: Severity measured by APACHE-II, the Revised Trauma Score, and the Therapeutic Intervention Scoring System, and outcomes measured by mortality and the number of ICU and hospital days, were gathered prospectively on all adult air medical patients between July 1, 1990, and June 30, 1992. Patients less than 16 years old or those who were delivered to other hospitals were excluded. Patients were categorized as cardiac, acute trauma, and other. Origin of transfer and transfer times were included in the analysis. In all, 1,169 patients were studied--554 in the first year of the study, 615 in the second. In the first year, there were 185 P/N (33%) and 369 N/N (67%) flights. P/N patients were older (48.8 versus 44.5 years; P = .01) and were more likely to come from a scene (14% versus 5.7%; P = .001), but no differences were found with regard to sex or disease category. Mortality, the Therapeutic Intervention Scoring System, APACHE-II, number of ICU days, and number of hospital days were no different; nor were total flight times or times spent at the hospital or scene. In the second year, 89% of flights were N/N. Differences in age or origin were not observed. Severity levels and outcomes remained unchanged. Between 1987 and 1992, the proportion of cardiac patients decreased, and overall illness severity of transported patients increased. CONCLUSION: Two years of detailed prospective measurement of air medical patient characteristics and outcomes confirmed the initial finding that no significant differences in clinical outcomes could be identified between patients managed by P/N versus N/N crews.

Air Ambulances↗
PubMed1995

Heat-shock proteins in host-pathogen interactions: implications for cystic fibrosis.

The expression of heat-shock proteins by both pathogen and host cells during the phagocytosis of Staphylococcus aureus and Pseudomonas aeruginosa, two bacterial species that colonize the airways of patients with cystic fibrosis, probably contributes to pulmonary inflammation in cystic fibrosis. Here, we discuss the likely signals for heat-shock-protein induction within host and bacterial cells.

Bacterial Proteins↗
PubMed1995

Use of risk projection models for the comparison of mortality from radiation-induced breast cancer in various populations.

The aim of our study is to compare lifetime risk estimates for radiation-induced breast cancer between various populations. Some epidemiological studies, mainly on Japanese A-bomb survivors, but also on North American populations irradiated for medical reasons, provide risk coefficients for excess mortality from breast cancer after exposure to ionizing radiation. For this comparative study, these risk coefficients have been transferred into the Japanese, American, and French populations, using demographic data, risk projection models, and assuming an individual acute exposure. The lifetime risk estimates are similar in the three populations when the additive projection model is used because of the similarity of the life tables of the three countries. However, using the multiplicative model, large differences appear due to the discrepancies in the baseline breast cancer rates between the Japanese and Occidental populations. It is for this reason that transfer of risk coefficients fitted on the Japanese population data must be considered with caution when applied to an Occidental population. Lifetime risk estimates for a given population, the French population for example, are largely dependent on the risk coefficients considered from various epidemiological studies. Nevertheless, for each source of data, they are higher with the multiplicative model than with the additive one. Moreover, it should be noted that data from medical irradiation lead to higher risk estimates when using the additive model, whereas studies of the A-bomb survivors lead to higher risk estimates with the multiplicative model. This comparative study points out the variations of the lifetime risk calculations according to the baseline breast cancer mortality rates of the three populations and with the use of different mathematical projection models.

Adult↗
PubMed1995

[Mucoviscidosis: in children and adults].

Because the lifespan of patients with cystic fibrosis is now longer, both pediatricians and adult care physicians are involved in the health care strategy. Respiratory manifestations occur due to bronchial dilatation and chronic bronchial infection, mainly due to Staphylococcus aureus and Pseudomonas. Episodes of adult infection are frequent and death usually results from respiratory failure. Characteristically, the disease also involves exocrine pancreas insufficiency. Other intestinal tract manifestations include meconial ileus and liver disease which may reach the stage of biliary cirrhosis. Nutritional disorders are frequent. Clinically there are respiratory and digestive tract disorders, pansinusitis and frequent nasal polyposis, sometimes associated with diabetes mellitus or joint pain. Male sterility results from bilateral agenesia of the vas deferens and in the female, fertility is decreased although pregnancy is possible. Clinical presentation suggests the diagnosis which is confirmed by a sweat test and genetic analysis. Care should be provided by a centre specialized in cystic fibrosis. The main treatments rely on respiratory physical therapy, antibiotics and gastroprotected pancrease extracts.

Adolescent↗
PubMed1994

Unexpected inactivation of acceptor consensus splice sequence by a -3 C to T transition in intron 2 of the CFTR gene.

Cystic fibrosis is caused by mutations in the cystic fibrosis transmembrane conductance regulator gene (CFTR). Analysis of DNA from a pancreatic sufficient patient by means of denaturing gradient gel electrophoresis (DGGE) and subsequent DNA sequencing led to the identification of a novel potential splice mutation and a novel missense mutation in the CFTR gene. One C to T substitution (297-3C-->T) was found at the splice acceptor site of intron 2 and a T to C substitution at 1213 was found in exon 7. To determine the effect of the potential splicing mutation on the patient's CFTR transcripts and by taking advantage of the "illegitimate" transcription phenomenon, RNA from EBV-lymphoblastoid cells was reverse transcribed and amplified by the polymerase chain reaction (PCR). Direct sequencing of the PCR product revealed that the transcript from the chromosome with the 297-3C-->T mutation exhibited the skipping of exon 3.

Adult↗
PubMed1994

[Cystic fibrosis: gynecological and obstetrical aspects].

Survival in patients with cystic fibrosis has considerably improved over the last years. Young adults are particularly concerned. Fertility in these patients is greatly decreased, especially in men due to obstructive azoospermia. In women, intra-uterine insemination with her spouse's sperm can overcome anomalies in the cervical glair. Several pregnancies in patients with cystic fibrosis have been reported, especially in women with a mild form of the disease. Prematurity is frequent, about 35% as is perinatal mortality related to the mother's status. When lung involvement is severe leading to major obstruction and hypoxia, cor pulmonae and denutrition, pregnancy remains a contraindication. Care for pregnant women (when pregnancy is possible) should rely on a multidisciplinary team and include a rigorous nutritional and anti-infection support.

Adult↗
PubMed1993

[Radiation-induced tumors of the nervous system in man].

The risk of developing a tumor of the nervous system in humans is analysed in several studies of populations, exposed to ionising radiation for medical reasons, or exposed to military or occupational radiation. The main data come from series of patients who underwent radiotherapy during childhood: a high incidence of tumors of the nervous system is found after irradiation of one to a few grays as treatment of a benign disease (especially tinea capitis), as well as after irradiation at higher doses of a few tens of grays for the treatment of cancer (in particular cerebral irradiation in acute lymphoblastic leukaemia). The type of radiation-induced tumors is variable, but meningioma is more frequent after low doses and glioma and sarcoma after higher doses used in the treatment of neoplastic diseases. A dose-effect relationship appeared between the risk of tumor of the nervous system and the radiation dose. The risk was higher when radiation was delivered at a younger age. Much less data are available after radiotherapy in the adulthood, but an increased risk of cerebral tumor appears in the series of ankylosing spondylitis patients. As for the exposures to radiodiagnosis exams, the main problem is the risk of cerebral tumor in children whose mother has undergone abdominal or pelvic X-rays during pregnancy. No risk of neurologic tumor was found in the A-bomb survivors irradiated at Hiroshima and Nagasaki. Occupational exposure to ionising radiation has been incriminated in the first radiologists exposed to high doses. In nuclear industry workers, the results of epidemiological studies are contradictory and at the present time it is not possible to link their radiologic exposure with a risk of tumor of the nervous system. In populations living near nuclear plants, mortality due to tumors of the nervous system was not increased.

Adolescent↗
PubMed1992

Comparison of aeromedical crew performance by patient severity and outcome.

STUDY PURPOSE: One of the continuing controversies in aeromedical transport involves crew composition. Since 1987, we have used both physician/nurse (P/N) and nurse/nurse (N/N) crews to staff two identically equipped helicopter ambulances. The purpose of this study was to compare the severity of illness or injury and outcomes of patients transported by P/N and N/N crews. DESIGN: Retrospective cohort. METHODS: Data were obtained from the air ambulance and medical records of all aeromedical transfers between September 1, 1987, and August 31, 1988. Patients less than 16 years old or transferred to other hospitals were excluded. Severity of illness or injury was measured by Revised Trauma Score, APACHE-II, and Therapeutic Intervention Scoring System; outcome measures were mortality, and ICU and hospital lengths of stay. Patients were categorized as cardiac, trauma, or other. Origin of transfer (scene, emergency department, or hospital) and transfer times were included in the analysis. MEASUREMENTS AND MAIN RESULTS: Six hundred fifty-nine patients were studied--418 P/N and 241 N/N. No differences were found between P/N and N/N groups with regard to sex, Revised Trauma Score, APACHE-II, or Therapeutic Intervention Scoring System, although P/N patients were younger (45.7 versus 50.9 years, P = .001), included more cardiac (40% versus 36%) and trauma (38% versus 30%) patients (P = .002), and were more likely to have been transferred from an ED (68% versus 51%) or scene (7% versus 2%) (P = .001). Mortality, ICU length of stay, and hospital length of stay of P/N and N/N patients were not different, nor was time spent at the scene or hospital. Subgroup analysis did not alter these results. CONCLUSION: No objective differences in outcome of patients were found between P/N and N/N teams. Although small differences were found in types of flights taken by P/N and N/N teams, there were no differences in objective measures of severity between the two teams. We find no objective evidence to prefer one crew composition over another.

Adult↗
PubMed1992

[Risks of cancer among workers of the nuclear industry].

The epidemiological studies on cancer incidence or mortality among workers in the nuclear industry have been reviewed in a comparative manner. The results concerning workers monitored for external radiation or internal contamination and those on female workers have been analysed separately. A lower cancer risk was found in most studies, which is explained by the "healthy worker effect"; no difference was found between the workers with or without a radiation record. A high rate was found for a few cancers at specific sites, but results were variable in the different studies and no relationship was found between cumulative dose and excess mortality due to cancer. A link between ionizing radiation, multiple myeloma and prostatic cancer was indicated in more than one study; in the latter case, there might be a relationship with internal contamination, especially by tritium. In spite of the difficulties and limitations involved, it is important to pursue these studies and pool them, in order to directly evaluate the risks of cancer following exposure to low-dose radiation and low dose rates, instead of calculating these by extrapolation from high doses.

Adult↗
PubMed1990

[4 years after Chernobyl: medical repercussions].

The nuclear accident at Chernobyl accounted for an acute radiation syndrome in 237 persons on the site. Triage was the initial problem and was carried out according to clinical and biological criteria; evaluating the doses received was based on these criteria. Thirty one persons died and only 1 survived a dose higher than 6 Gy. Skin radiation burns which were due to inadequate decontamination, greatly worsened prognosis. The results of 13 bone marrow transplantations were disappointing, with only 2 survivors. Some time after the accident, these severely irradiated patients are mainly suffering from psychosomatic disorders, in the USSR, some areas have been significantly contaminated and several measures were taken to mitigate the impact on population: evacuating 135,000 persons, distributing prophylactic iodine, establishing standards and controls on foodstuff. Radiation phobia syndrome which developed in many persons, is the only sanitary effect noticed up to now. Finally, in Europe, there was only an increase in induced abortions and this was totally unwarranted. If we consider the risk of radiation induced cancer, an effect might not be demonstrated.

Abnormalities, Radiation-Induced↗
PubMed1989

[Blood amylase: a biological marker in irradiation accidents? Preliminary results obtained at the Gustave-Roussy Institut (GRI) and a literature review].

The retrospective evaluation of the dose after an irradiation accident is of paramount importance; it allows an adequate selection of patients and the most appropriate treatment can then be proposed. Classical physical dosimetry often lacks precision for dose assessment in such accidents. Cytogenetics, usually more reliable, is not 100% accurate and cannot be used in some particular instances. At the Institut Gustave-Roussy, we studied amylasemia in 15 patients who received a total body irradiation (TBI) for bone marrow grafting, at various dose levels (10, 2 and 1.35 Gy). Hyperamylasemia was found to be constant and dose-dependent. Ten additional patients given a localized irradiation of 2 Gy in the Waldeyer ring had a similar rise in amylasemia as did TBI patients who had received the same dose. In contrast, 13 patients given a pancreatic irradiation (as part of a localized abdominal irradiation) did not show any increase in amylasemia. This study seems to confirm reported data, which suggested that post-TBI hyperamylasemia is almost only related to salivary gland irradiation. Amylasemia could possibly be used as a "biological dosimeter"; however, the dose-effect relationship should be more precisely defined, as well as individual variations. Moreover, the definition of a "threshold-dose" below which hyperamylasemia can never be detected, would be of interest for radioprotection.

Amylases↗
PubMed1988

Effect of theophylline on gastroesophageal reflux in patients with asthma.

A possible role of methylxanthines in the high incidence of gastroesophageal reflux (GER) in patients with asthma has been suggested. Therefore, we used a randomized, double-blind, crossover design to compare the effects of a 1-week conventional theophylline treatment and a 1-week placebo treatment in 16 adult patients with asthma. No oral or parenteral glucocorticoids were administered, but seven patients were taking inhaled corticoids. All patients needed inhaled adrenergic drugs. At the end of each period of theophylline or placebo treatment, the patients were carefully questioned with respect to respiratory and digestive symptoms, forced expiratory flows were measured, and GER was assessed by prolonged nocturnal intraesophageal pH monitoring. Peak expiratory flow was measured three times a day throughout the study. No significant increase in GER was found with theophylline compared to placebo, and forced expiratory flows improved with theophylline (p less than 0.05 for FEV1 and p less than 0.01 for peak expiratory flow rate). There was no correlation between GER, the duration of asthma, and forced expiratory flows. Thus, our study failed to demonstrate any adverse effect of a slow-release theophylline preparation on GER in patients with asthma. These results further suggest that the presence of GER is not a contraindication to the use of a slow-release theophylline in subjects with asthma.

Adrenergic beta-Agonists↗