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Biomedical subjects

H Marotte

Publications and source records attributed to H Marotte.

At least 19 recordsLinked to original sources

Extensive multiallelic analysis of the relationship between HLA-DRB1 and rheumatoid arthritis using a Bayesian partition model.

To analyse the association between individual HLA-DRB1 locus genotypes and rheumatoid arthritis (RA) susceptibility, taking in account the multiallelic nature of the shared epitope (SE). In total, 538 patients and 536 controls were genotyped for 12 alleles of the HLA-DRB1 locus. A Bayesian partition model and multivariate logistic models were used to assess the role of the SE and of its individual components. The SE was associated with RA susceptibility (odds ratio (OR) 2 versus 0 SE copy=9.99 (95 CI 4.69-15.30) and OR 1 versus 0 SE copy=3.16 (95% CI 2.42-4.12)). The Bayesian partition model supplied a permutation of the HLA-DRBA locus alleles ordered by increasing disease risk. Alleles associated with highest risks are those that code for the SE. The individual OR estimations for the HLA-DRB1 locus genotypes went from OR=1.00 (95% CI 1.00-1.25) for the less associated genotype to OR=21.40 (95% CI 8.02-65.79) for the most associated one. In conclusion, the allele order risk and the OR estimations for individual genotypes of the HLA-DRB1 locus were consistent with the SE theory. Using an exploratory statistical method without a priori hypothesis, our study allowed a detailed analysis of the multiallelic nature of the SE.

Adult↗

Etanercept treatment for three months is safe in patients with rheumatological manifestations associated with hepatitis C virus.

OBJECTIVE: The treatment of the rheumatological manifestations associated with hepatitis C virus (HCV) remains difficult. To examine the safety of anti-tumour necrosis factor-alpha treatment, nine patients having rheumatological manifestations associated with HCV were treated with etanercept 25 mg twice a week for 3 months. METHODS: Five patients had a positive viral load at study entry (Group I), four were negative (Group II). Clinical data recorded were: disease duration, painful and swollen joint count, patient global and physician global assessment, the number of 18 specified fibromyalgia tender points and the Health Assessment Questionnaire score. Laboratory studies included checking for the presence of cryoglobulinaemia and transaminase levels. Quantitative HCV viral RNA was performed by real-time polymerase chain reaction (PCR). RESULTS: At 3 months, no patient was found to have evidence of increased hepatic inflammation based on serial serum transaminase levels. In the five patients from Group I with detectable HCV RNA, no significant viral load increase was observed. No reactivation was observed in the four patients from Group II with undetectable HCV RNA. The effect on the clinical rheumatological manifestations was more heterogeneous but appears to be lower than that observed in rheumatoid arthritis. CONCLUSION: In this phase II open short-term study, etanercept appeared to be safe in patients with articular manifestations associated with HCV.

Antirheumatic Agents↗

The association between periodontal disease and joint destruction in rheumatoid arthritis extends the link between the HLA-DR shared epitope and severity of bone destruction.

OBJECTIVE: To evaluate a possible association between wrist and periodontal destruction in rheumatoid arthritis, and between periodontal destruction, dry mouth, and labial salivary gland biopsy and the contribution of genetic factors (the shared epitope (SE) and IL1B (+3954) or TNFA (-238 or -308) gene polymorphisms). METHODS: 147 patients with rheumatoid arthritis were enrolled. Periodontal damage was defined according to the Hugoson and Jordan criteria on panoramic dental x rays. Typing for the SE and cytokine polymorphisms was undertaken by enzyme linked oligosorbent assay. Odds ratios (OR), relative risk (RR), and chi2 values were calculated to quantify associations. RESULTS: An association was observed between wrist and periodontal bone destruction (chi2=11.82; p<0.001): 63 patients had both wrist and periodontal destruction, 31 had wrist destruction alone, 20 had periodontal destruction alone, and 33 had no destruction at either site. An association was seen between a positive labial salivary gland biopsy and periodontal bone destruction (RR=2.73 (95% CI, 1.35 to 5.51), p<0.01, n=41) or wrist bone destruction (RR=4.52 (1.96 to 10.45), p<0.001, n=41). The SE was associated with wrist bone destruction (OR=2.5 (1.16 to 5.42), p<0.05) and periodontal bone destruction (OR=2.2 (1.04 to 4.84), p<0.05). No association was found between the selected cytokine polymorphisms and bone destruction. CONCLUSIONS: A strong association was found between wrist and periodontal bone destruction. The destruction risk was further increased in patients with sicca syndrome. The SE appears to be a severity genetic marker for both wrist and periodontal bone destruction.

Aged↗

The shared epitope is a marker of severity associated with selection for, but not with response to, infliximab in a large rheumatoid arthritis population.

OBJECTIVE: To determine whether joint destruction, indication for, and response to infliximab in rheumatoid arthritis are associated with the shared epitope (SE) or selected cytokine gene polymorphisms (interleukin (IL) 1B, IL1-RN, and tumour necrosis alpha). METHODS: In a large rheumatoid arthritis population of 930 patients from the same area (Rhône-Alpes, France), patients with (n = 198) or without infliximab treatment (n = 732) were compared according to their genetic status. Clinical, biological, and radiological data were collected. Typing for SE status and cytokine polymorphisms was carried out using enzyme linked oligosorbent assay. Statistical analysis was by chi(2) testing and calculation of odds ratios (OR). RESULTS: A dose relation was observed between the number of SE copies and joint damage in the whole rheumatoid population (OR, 1 v 0 SE copy = 2.38 (95% confidence interval, 1.77 to 3.19), p<0.001; OR 2 v 0 SE copy = 3.92 (2.65 to 5.80), p<0.001. The SE effect increased with disease duration but was not significant before two years. Selection for infliximab treatment (n = 198) was associated with increased disease activity, joint damage, and the presence of the SE with a dose effect. In all, 66.2% patients achieved an ACR20 improvement. No clinical or genetic factors were able to predict the clinical response to infliximab. CONCLUSIONS: This post-marketing study in a large cohort of rheumatoid arthritis patients indicates a linkage between rheumatoid arthritis severity, selection for treatment with infliximab, and the presence and dose of the SE.

Adult↗

Lupus erythematosus with leflunomide: induction or reactivation?

BACKGROUND: Leflunomide is a new oral disease modifying antirheumatic drug with a good safety profile. CASE REPORT: The first case of lupus erythematosus in a 58 year old white woman after administration of leflunomide for primary Sjögren's syndrome is reported. The relationship between induced lupus and leflunomide was confirmed by the resolution of the skin rash when the drug was stopped and its recurrence when it was reintroduced following a dose-response effect. DISCUSSION: Peripheral blood cells from this patient, from 15 patients with rheumatoid arthritis, and from healthy controls were used in a bioassay, which suggested that leflunomide affected the Th1/Th2 balance. Such a side effect might be related, in part, to the anti-tumour necrosis factor alpha activity of leflunomide.

Antirheumatic Agents↗

Infliximab-induced aseptic meningitis.

We report an episode of aseptic meningitis in a 53-year-old man, who was treated with infliximab for active rheumatoid arthritis. He had acute, severe muscle pain after initial infusion of the drug, and similar symptoms with a transient lymphocytic meningitis after a subsequent infusion. We measured no change in antibodies to nuclei, DNA, or to neurones. Functional antibodies to infliximab were not induced and concentrations of tumour necrosis factor a in spinal fluid were not raised. This adverse reaction to infliximab might have been caused by inability of the drug to enter the central nervous system.

Antibodies, Monoclonal↗

A routine assay for the direct analysis of HLA-DR-related shared epitope and B27 alleles in chronic inflammatory arthritis.

Knowledge of the genetic background of patients with inflammatory arthritis may be useful for disease management. The main markers are the HLA-DR-associated Shared Epitope (SE) for Rheumatoid Arthritis (RA) and HLA-B27 for ankylosing spondylitis. We have developed a simple molecular biology-based test to provide this essential information. HLA targets are amplified by polymerase chain reaction (PCR), then simultaneously analyzed using 16 individual hybridization reactions in two 8-well ELISA strips with colorimetric detection. Concordance was evaluated using a cohort of RA patients with known genotype. Using this new assay, 100% concordance was observed with conventional genotyping in RA patients both for HLA-DR SE and B27 genotypes. Seventy-three percent of the patients with destructive RA had at least one susceptible allele within SE, compared to 38% of those patients with non-destructive disease. This new assay, which requires minute amount of blood, could be used to determine the genetic background of inflammatory arthritis, particularly in non-specialized settings and for large-scale clinical trials.

Adolescent↗

Testing of the AVL OPTI 1 portable blood gas analyzer during inflight conditions.

The "AVL OPTI 1" (AVL Medical Instruments, Saint-Ouen l'Aumone, France), a completely automated portable blood gas analyzer, was chosen because of its accuracy under usual sea-level conditions and because of its new technology which broadens the possibilities for in-flight blood determinations: a) a single use cassette made of plexyglass containing the measurement chamber and the aligned sensors required for pO2, pcO2 and pH determination; b) calibration coefficients memorized in a bar code label fixed on the packing material; c) a quality control of each individual cassette prior to the measurement and at least once a day by two standard reference cassettes simulating high and low levels of pH, pcO2 and pO2; and d) a fully automatic introduction of the blood sample. The complete analytical cycle requires about 3 min with a sample volume of 80 microL of whole blood. After the measurement, the cassette containing blood sample is destroyed. Moreover, this device uses optical electrodes or "optodes" (fluorescence sensors). We tested the accuracy and imprecision of pO2 and pcO2 sensors on fresh blood which was equilibrated with four different gas mixtures at four different altitudes (250, 8000, 10,000 and 13,000 ft), simulated in a decompression chamber. Gas measurement optodes had linear responses and were accurate for all measured pO2 and pco2 values (n = 66), except for at high values of PO2 (>150 mmHg) and pco2 (>65 mmHg). The pressure value given by the AVL OPTI 1 was controlled before the experiment began and during the different depression levels. Barometric pressure results showed: a) concordance of pressure values with those of ground instrumentation; b) stable response; and c) absence of hysteresis. We conclude that the performance of the AVL OPTI 1 is satisfactory during inflight conditions.

Aerospace Medicine↗

Positive pressure generation by pneumatic and electronic O2 regulators: a bench experimental evaluation.

BACKGROUND: The introduction of advanced anti-G protection into agile fast fighter aircraft may result in the regular use of positive pressure breathing (PPB) for G protection by aircrew. Since PPB results in an external additional work of breathing (WoB), we compared the mechanical performance of the pneumatic and electronic O2 regulators designed for "Mirage 2000" and "Rafale" aircraft. HYPOTHESIS: Since mask pressure is regulated by the electronic device in relation to flow, mask pressure will remain constant throughout the respiratory cycle, so that PPB-related additional WoB will be less with the electronic regulator. METHODS: In a bench dynamic study performed with a sinusoidal pump, we measured variations in mask pressure (deltaP) and calculated WoB at 0, 3 and 6 kPa of PPB (0, 30 and 60 cm H2O, respectively), for 0.5, 1 and 2 L of volume and for 10, 15 and 20 cycles per minute of respiratory rate. RESULTS: We found that, compared with the pneumatic device, inspiratory and expiratory WoB with the electronic device were respectively lower by approximately 25% (p < 0.05) and by approximately 10% (NS) at 3 and 6 kPa of PPB, for all respiratory conditions. Nevertheless, we also observed remaining variations in mask pressure with the electronic regulator, due to complex impedance of the inspiratory circuit, since the device uses the pressure measured into the regulator. CONCLUSIONS: We concluded that the electronic control of mask pressure is relatively efficient but that the device would be improved by placing the site of the pressure measurement into the mask.

Aerospace Medicine↗

Effects of chest wall counterpressures on lung mechanics under high levels of CPAP in humans.

We assessed the respective effects of thoracic (TCP) and abdominal/lower limb (ACP) counterpressures on end-expiratory volume (EEV) and respiratory muscle activity in humans breathing at 40 cmH2O of continuous positive airway pressure (CPAP). Expiratory activity was evaluated on the basis of the inspiratory drop in gastric pressure (DeltaPga) from its maximal end-expiratory level, whereas inspiratory activity was evaluated on the basis of the transdiaphragmatic pressure-time product (PTPdi). CPAP induced hyperventilation (+320%) and only a 28% increase in EEV because of a high level of expiratory activity (DeltaPga = 24 +/- 5 cmH2O), contrasting with a reduction in PTPdi from 17 +/- 2 to 9 +/- 7 cmH2O . s-1 . cycle-1 during 0 and 40 cmH2O of CPAP, respectively. When ACP, TCP, or both were added, hyperventilation decreased and PTPdi increased (19 +/- 5, 21 +/- 5, and 35 +/- 7 cmH2O . s-1 . cycle-1, respectively), whereas DeltaPga decreased (19 +/- 6, 9 +/- 4, and 2 +/- 2 cmH2O, respectively). We concluded that during high-level CPAP, TCP and ACP limit lung hyperinflation and expiratory muscle activity and restore diaphragmatic activity.

Adult↗

[Russian intra vehicular space suit and cold protection].

During space flights, astronauts use equipment allowing protection against many environmental factors. During tests realised in Russia, space suit efficiency was evaluated particularly concerning cold protection capacity in cold water (3 degrees C) and in cold air (-30 degrees C). Obtained results prove that this equipment allows to prevent hypothermia in cold water and ensure thermal comfort in cold air.

Cold Temperature↗

Effect of zolpidem on sleep and ventilatory patterns at simulated altitude of 4,000 meters.

The purpose of this study was to assess the effect of zolpidem 1 0 mg, a new imidazopyridine hypnotic drug, on sleep and respiratory patterns at a simulated altitude of 4,000 meters. Eight male subjects spent three nights in a decompression chamber. The first study night was spent at the ambient pressure corresponding to sea level. The two other nights were spent at a simulated altitude of 4,000 meters with either zolpidem or a placebo in random order according to a double-blind, crossover design. All subjects showed periodic breathing (PB) during sleep at simulated high altitude. Furthermore, altitude was associated with decreases in total sleep time (TST), slow-wave sleep (SWS), and REM sleep, and with significant increases in Stage 1 duration and in the arousal index. Most arousals were synchronous with the hyperpneic phase of PB. The main finding of our study is that zolpidem improved sleep characteristics at high altitude, inducing a decrease in sleep onset latency (placebo, 22 +/- 12 min versus zolpidem, 10 +/- 6 min), an increase in SWS duration (placebo, 46 +/- 28 min versus zolpidem, 69 +/- 28 min), and a reduction in the arousal index during SWS (placebo, 7.4 +/- 4.1 per h versus zolpidem: 2.4 +/- 1.0 per h). Furthermore, none of the respiratory parameters were significantly affected by zolpidem in any sleep stage. In conclusion, zolpidem improved sleep quality at high altitude without adversely affecting respiration.

Adult↗

[Changes in the blood flow of the primary carotid and its branches during modifications of the O2 and CO2 composition of alveolar gas].

We measured common carotid blood flow using a range gated Doppler velocimeter, and internal and external blood velocities using a continuous Doppler in 20 lowlanders at sea level, under normal barometric pressure, in 10 subjects in an altitude chamber under a barometric pressure of 462 Torr (61.6 KPa) and then in 5 of them over a 3-weeks period at 3850 m of elevation (475 Torr = 63.3 KPa). The same measurements were also performed in 20 permanent residents at 3850 m. Common carotid blood flow was 15% higher in all subjects exposed to high altitude, due to a lowering in downstream resistances since systemic blood pressure did not change at high altitude. The increase in common carotid blood flow was the result of an immediate increase in internal carotid blood velocities observed in the altitude chamber as well as after the arrival at high altitude, but a few days later those velocities in the internal carotid artery declined to values similar to those observed at sea level. In the same time velocities in external carotid artery rose at high altitude, remained steadily elevated and the result is a permanent increase in common carotid blood flow at altitude. In all subjects we performed the same measurements, during an acute inhalation of gas mixtures to try to quantify the mechanisms controlling the changes in common carotid blood flow while changing gas inhalation. In the limits of the variations in PO2 (60 to 400 Torr) and in PCO2 (30 to 50 Torr) the stimulation by CO2 is twice more efficient than the O2 stimulation on vasomotion.

Adult↗

Distribution of common carotid blood flow, measured by Doppler, in man at high altitude.

The aim of the work was to estimate the possible changes induced by high altitude in the distribution of the common carotid arterial blood flow towards the internal and external carotid arteries. Common carotid blood flow and internal and external blood velocities were measured in 20 lowlanders at sea level, in 5 of them over a 3-week period at 3800 m and in 20 permanent residents of this high altitude. Internal and external blood velocities were recorded with a continuous Doppler and blood flow was recorded by range-gated Doppler velocimeter. Common carotid blood flow was 15% higher in all subjects exposed to high altitude due to a lowering in downstream vascular resistance since systemic blood pressure did not change at high altitude. The increase of blood flow in the common carotid was the result of a rise mainly in the external carotid blood flow.

Acclimatization↗

Transport aircraft crew and decompression hazards: study of a positive pressure schedule.

The protection of the transport aircraft crew against cabin decompression hazards at high altitude (Z less than 45,000 ft) (13,700 m) is achieved by positive pressure breathing (PPB). Currently, many PPB schedules are used. Our research was performed to propose a PPB schedule, using the hypothesis of a decompression at high altitude, including a stay at the flight level and an emergency descent at the rate of 15,000 ft.min-1. The measures were arterial oxygen saturation, heart rate, speech capabilities, and psychomotor performance. The tests were conducted up to 45,000 ft. They show that the best protection at 45,000 ft is afforded when the PPB is included between 2 and 2.5 kPa (15 to 18.75 mm Hg).

Adult↗

Rapid decompression of a transport aircraft cabin: protection against hypoxia.

The hypoxic hazard after rapid decompression in transport aircraft was evaluated as a function of the current means of protection, including the role of the inhaled oxygen fraction (FIO2) prior to decompression. The decompressions were made in 2 s; the initial altitude was 8,000 ft and the final altitude was 16,000-45,000 ft. The physiological measurements were arterial oxygen saturation, heart rate, ventilatory frequency, and gaseous analysis in the mask. Results show that FIO2 prior to decompression is not very significant, but the delay before donning the oxygen system seems to be the most limiting factor against tolerance to hypoxia.

Aerospace Medicine↗