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Biomedical subjects

P Gajdos

Publications and source records attributed to P Gajdos.

At least 73 records · Page 4Linked to original sources

Immunoglobulin A levels in bronchial samples during mechanical ventilation and onset of nosocomial pneumonia in critically ill patients.

Local immunoglobulins play a key role in host defense against lung infection. We investigated the pattern of evolution of bronchial albumin, IgA, and IgG levels in ventilated ICU patients in relation to nosocomial pneumonia. Immunocompetent, critically ill patients underwent serial blood and bronchial protein determinations on Day 1 (intubation day), and on Days 3, 7, 10, and 14. The variations in proteins levels were compared with corresponding Day 1 values in the whole population, and between patients who developed lung infections (Group A) and the remaining population (Group B). Forty-four patients were included into the study. In the whole population, when compared with the baseline value, bronchial IgA/albumin ratio increased significantly (Day 3, +58%, p = 0.04); Day 14, +171%, p < 0.01), but serum IgA/albumin and serum and bronchial IgG/albumin ratios did not change significantly. In Group A, the increase in the IgA/albumin ratio was less than in Group B (Day 3, +15% versus +87%, p = 0.04; Day 14, +29% versus +210%, p < 0.01). No significant differences were observed between the two groups for bronchial and plasma albumin and IgG levels and for bronchial polymorphonuclear elastase levels. Bronchial IgA production was enhanced in ventilated patients. A reduction in this enhanced bronchial IgA production might account for the development of nosocomial pneumonia.

Adult↗

Long-term effects of nasal intermittent positive-pressure ventilation on pulmonary function and sleep architecture in patients with neuromuscular diseases.

STUDY OBJECTIVE: This article evaluates the long-term clinical and physiologic effects of nocturnal nasal intermittent positive-pressure ventilation (NIPPV) in patients with neuromuscular disease. METHODS: Before and after 18 +/- 2 months of NIPPV, we measured during the daytime arterial blood gases, lung mechanics, and respiratory muscle strength in 8 patients (51 +/- 5 years; mean +/- SEM). Sleep parameters were also evaluated at 10 +/- 2 months. RESULTS: All patients tolerated NIPPV and none required hospitalization during follow-up. After NIPPV, daytime arterial PO2 increased (71 +/- 4 to 81 +/- 2 mm Hg; p < 0.05) and arterial PCO2 decreased (46 +/- 3 to 41 +/- 1 mm Hg; p < 0.05). The change of PaO2 after NIPPV was related to its baseline value (r2 = 0.78, p < 0.05). Vital capacity (50 +/- 6% predicted), total lung capacity (63 +/- 4% predicted), alveolar-arterial oxygen gradient (20 +/- 3 mm Hg), and maximal inspiratory (39 +/- 9% predicted) or expiratory (32 +/- 5% predicted) pressures did not change after NIPPV. The apnea-hypopnea index fell from 22 +/- 6 to 1 +/- 1 (p < 0.05), and both sleep architecture and sleep efficiency (from 59 +/- 8% to 83 +/- 5%; p < 0.05) were enhanced. The time spent with an arterial oxygen saturation (SaO2) value below 90% decreased from 160 +/- 53 min to 8 +/- 4 min (p < 0.05). Mean (88 +/- 3 to 95 +/- 1%; p < 0.05) and minimal nocturnal SaO2 (67 +/- 5 to 89 +/- 1%; p < 0.001) improved after NIPPV. CONCLUSIONS: In patients with neuromuscular disease, long-term NIPPV is well tolerated and easy to implement clinically. In these patients, long-term NIPPV improves daytime arterial blood gas values and sleep-disordered breathing. However, it does not modify lung mechanics or respiratory muscle strength.

Adult↗

[Treatment of Guillain-Barré syndrome by plasma exchange: proposal of a therapeutic strategy].

Although the favorable effect of plasma exchange (PE) has been demonstrated in Guillain-Barré syndrome, the optimal number of PE and management at different degrees of gravity remain to be ascertained. A new controlled multicentric trial is therefore being conducted since 1986. Mid-term results show that 2 PE give better results than 0 in patients who are still able to walk. Inversely, 6 PE do not give better results when ventilatory assistance was initially required. It is therefore logical to propose 2PE as early as possible. Two supplementary PE can be used in case of disease progression. Use of high dose immunoglobulins is not justified except when PE is contraindicated.

Humans↗

International forum: France. The national survey of plasma exchange and therapeutic cytapheresis in France.

Created in 1985, the French Society of Haemapheresis (SFH) Registry is the largest data base of plasma exchange (PE) in the world. Data analysis shows that neurological diseases are the most frequent indications for PE in France and that improvement in technique has reduced early complications. As for therapeutic cytapheresis, peripheral blood stem collection represents the major activity (64%). The second most common activity is UVA extracorporeal photochemotherapy.

Cytapheresis↗

Kinetics of elimination and acute consequences of cerebral air embolism.

The pathophysiology of arterial air embolism inducing brain injuries remains unclear. Previous experiments demonstrated the usefulness of computed tomography (CT) in the detection of air emboli in canine brain. This canine study investigates CT's ability to detect small air bubbles and to determine the kinetics of air elimination from cerebral arteries and its relationship with clinical, electroencephalographic (EEG), and histological manifestations. CT detects small air embolism, and intracerebral air volume strongly correlates with injected air dose (r2 = 0.86, p = 2 x 10(-3)). Air clearance time significantly depends on intracerebral air volume (r2 = 0.86, p = 0.04) and on the number of bubbles (r2 = 0.71, p = 0.03), whereas half-life of air elimination does not. No relationship was found between injected air dose, air clearance time, intracerebral volume of air, and clinical, EEG, and histological findings. The data indicate that CT accurately detects small air bubbles in the early course of cerebral air embolism, that air elimination from cerebral arteries follows a first-order compartment model, and that early CT findings do not correlate with clinical, EEG, and histological manifestations.

Animals↗

Severe community-acquired pneumococcal pneumonia. The French Study Group of Community-Acquired Pneumonia in ICU.

Streptococcus pneumoniae is the most frequent pathogen of severe community-acquired pneumonia (CAP) necessitating hospitalization. The main objective of this multicentre prospective study was to determine the value of clinical, biological, and radiological features for predicting pneumococcal etiology and to define prognostic factors. Streptococcus pneumoniae was isolated in 43/132 patients (33%) with CAP requiring ICU treatment. The mean age of the patients with pneumococcal pneumonia was 55 +/- 17 (SD) yrs and 34 were male. On admission, 14 patients with pneumococcal pneumonia were in shock, 24 were mentally confused, and 27 required mechanical ventilation during their hospitalization. Among the clinical, biological, and radiological features, fever > 39 degrees C, pleuritic chest pain, lobar distribution or alveolar consolidation, and an increase in immature granulocytes > or = 5% of WBC were more frequent in pneumococcal pneumonia than in other etiologies. Mortality was 35%. Fatal outcome was significantly related to the presence of impaired alertness, septic shock, mechanical ventilation, acute renal failure, and bacteremic pneumonia.

Adult↗

Involvement of human muscle acetylcholine receptor alpha-subunit gene (CHRNA) in susceptibility to myasthenia gravis.

The muscle acetylcholine receptor is the major target of the autoimmune response in generalized myasthenia gravis. To investigate the role of the gene encoding the alpha subunit of the receptor (CHRNA), two stable polymorphic d[(GT).(CA)]dinucleotide repeats, designated HB and BB, were characterized within the first intron of CHRNA. The HB*14 allele conferred a relative risk for myasthenia gravis of 2.5 in 81 unrelated patients compared with 100 control subjects. Very significantly, family analysis based on haplotype segregation data indicated that parental haplotypes associated with HB*14 always segregated to the child with myasthenia gravis (P < 0.0002 for the comparison with the transmission of haplotypes not bearing HB*14), whereas their transmission to unaffected siblings was equilibrated. Myasthenia gravis patients also showed a high frequency of microsatellite variants unseen in controls. These findings implicate the CHRNA in susceptibility to myasthenia gravis.

Adolescent↗

Human IgG monoclonal autoantibodies against muscle acetylcholine receptor: direct evidence for clonal heterogeneity of the antiself humoral response in myasthenia gravis.

Human hybridomas were established from myasthenia gravis (MG) patients and screened using a fast and sensitive cell ELISA with the rhabdomyosarcoma cell line TE671. In a first series of 14 fusions using a standard protocol, 36 positive clones were detected and maintained for three passages. The number of clones in each fusion was correlated with in vivo titers of anti-acetylcholine receptor (AChR) autoantibodies. In a second series of four experiments, fusions were immediately followed by cell plating under limiting dilution conditions ('fusion cloning') providing eight stable hybridomas. These hybridomas produced monoclonal antibodies (mAbs) of IgG isotype reactive with TE671 cells, but not with AChR in solution using the radioimmunoprecipitation assay. Fine analysis of antigen specificity of these mAbs was performed using solid-phase ELISA against purified AChR from Torpedo (T-AChR) and immunoblot against recombinant chimaeric human AChR produced in bacteria. Five of the eight mAbs derived from the few patients whose antibodies showed cross-reactivity with T-AChR reacted against T-AChR. Of these five mAbs, two also reacted against chimaeric human AChR by immunoblotting. Furthermore, at least one of these two mAbs was capable of inducing antigenic modulation of labeled AChR with [125I]alpha-bungarotoxin from the surface of TE671 cells. These mAbs provide useful tools to explore the molecular basis of the structural and functional heterogeneity of the humoral anti-AChR response in myasthenia gravis.

Antibodies, Monoclonal↗

Association of Km3 allotype with increased serum levels of autoantibodies against muscle acetylcholine receptor in myasthenia gravis.

Association of immunoglobulin allotypes with myasthenia gravis was examined in a set of 84 patients presenting autoantibodies against muscle acetylcholine receptor (AChR). Km and G1m(f)/G1m(z) allotypes were determined by PCR-amplification followed by hybridization with allele-specific oligonucleotides. The Km3 kappa light chain allotype was found to be associated with significantly increased serum levels of anti-AChR autoantibodies in myasthenic patients (P = 0.014). We hypothesize that an allelic polymorphism of a regulatory (enhancer) sequence closely linked to the C kappa gene segment could account for our finding.

Alleles↗

Effects of mechanical ventilation with normobaric oxygen therapy on the rate of air removal from cerebral arteries.

OBJECTIVE: We conducted the current study to evaluate the removal rate of air embolism from cerebral arteries after spontaneous breathing at a low FIO2 in comparison with mechanical ventilation at an FIO2 of 1.0. DESIGN: Randomized, experimental trial. SETTING: Neuroimaging department at a veterinary school hospital laboratory. SUBJECTS: Nine anesthetized beagles undergoing mechanical ventilation with previous normal cranial computed tomography (CT) scan. INTERVENTIONS: In each dog, after a control scan, air was infused at a constant flow rate, via a catheter inserted into the internal carotid artery. CT scan was repeated until typical bubbles appeared. Immediately after, the animals were randomly assigned to breathe room air (group A), or to be mechanically ventilated at an FIO2 of 1.0 (group B). CT scan was again repeated every minute until the removal of all bubbles. We compared the volume of air infused per kg of body and brain weights, the lowest density among bubbles (Hounsfield units), the duration of radiologic findings, and the ratio of volume/duration (mL/kg/min) between the two groups, using the Mann-Whitney test. RESULTS: The volume of air infused per kg of body and brain weights and density were not significantly different between the two groups. The duration of radiologic findings was shorter (p < .02) in group B (7.0 +/- 4.7) than in group A (20.4 +/- 3.8), and the air removal rate from cerebral arteries (expressed as volume/duration of radiologic findings) was dramatically improved (p < .02) in group B (0.159 +/- 0.042) in comparison with group A (0.046 +/- 0.016). CONCLUSIONS: These results suggest that the removal rate of air from cerebral arteries is dramatically increased by mechanical ventilation at an FIO2 of 1.0. Consequently, the time of cerebral ischemia may be decreased, but the result does not account for the effects of each factor separately. Further studies are required to evaluate the clinical benefits of high FIO2 administration and of mechanical ventilation separately. However, the prompt application of mechanical ventilation with an FIO2 of 1.0 may be recommended when air embolism is suspected.

Animals↗

Correlation between decreased myocardial glucose phosphorylation and the DNA mutation size in myotonic dystrophy.

BACKGROUND: Myotonic dystrophy, the most common form of adult dystrophy, has been shown to be caused by amplification of CTG triplet repeat in the 3' untranslated region of a protein kinase gene located on chromosome 19. Impaired glucose metabolism has been suggested as a possible explanation of brain and skeletal muscle involvement in this multisystem disease. We investigated whether myocardial glucose metabolism is impaired in myotonic dystrophy and whether this impairment is related to the size of the mutation. METHODS AND RESULTS: The myocardial metabolic rate for glucose (MMRGlu, mumol.min-1.g-1), K1 (blood-to-tissue transfer constant), k2 (tissue-to-blood transfer constant), and k3 (phosphorylation rate constant) were determined in 7 control subjects and 12 patients with myotonic dystrophy by using parametric images generated from dynamic cardiac positron emission tomography (PET) and 18F-fluoro-2-deoxy-glucose studies. The expansion of the CTG triplet repeats was analyzed in patients with the probe cDNA25 after EcoRI digestion. Nonparametric tests were used to compare quantitative variables between control subjects and patients. The correlations between the size of the mutation and PET parameters were studied by linear regression. MMRGlu and k3 were significantly decreased in patients compared with control subjects (0.39 +/- 0.20 versus 0.64 +/- 0.25, P = .03, and 0.09 +/- 0.07 versus 0.24 +/- 0.21, P = .03, respectively), whereas K1 and k2 were not statistically different between control subjects and patients. MMRGlu and k3 correlate inversely with the length of the CTG triplet repeat (r = -.65 and P = .03 for MMRGlu, and r = -.85 and P = .001 for k3, respectively). CONCLUSIONS: In myotonic dystrophy, the observed reductions in MMRGlu and phosphorylation are inversely linked to the length of the mutation. This observation suggests that impaired modulation of a protein kinase involved in myocardial hexokinase activation may give a pathophysiological schema to relate the molecular defect and the abnormal myocardial metabolism in myotonic dystrophy.

Adult↗

Sleep-related respiratory disturbances in patients with Duchenne muscular dystrophy.

Sleep-related respiratory disturbances (SRD) in patients with muscle diseases may have significant clinical implications, because the patients frequently die at night. The aims of the study were to :1) assess the presence and severity of sleep-related respiratory disturbances in patients with Duchenne muscular distrophy (DMD); and 2) investigate the relationship of sleep-related respiratory disturbances to daytime symptoms and pulmonary function. We studied six clinically stable patients with Duchenne muscular dystrophy, mean age (+/- SD) 18 +/- 2 yrs. Vital capacity was 27 +/- 19% of predicted and daytime arterial oxygen tension (PaO2) was 10.9 +/- 1 kPa (range 8.9-12.4 kPa). The presence of daytime somnolence, insomnia, headache, nightmares and/or snoring was recorded. Four patients (67%) showed symptoms that suggest sleep-related respiratory disturbances. At night, the apnoea-hypopnoea index (AHI) was 11 +/- 6. The patients with more symptoms during the daytime had the highest AHI scores. Most of the apnoeas (85%) were central, particularly during rapid eye movement (REM) sleep. Sleep architecture was well-preserved. Arterial desaturation (> 5% below baseline) occurred during 25 +/- 23% of total time. AHI correlated with daytime PaO2, and AHI in REM sleep correlated with age. A stepwise multivariate analysis showed that PaO2 and, to some extent, the degree of airflow obstruction were significantly correlated with AHI. We conclude that sleep-related respiratory disturbance are frequently present in patients with Duchenne muscular dystrophy. Therefore, physicians should look for symptoms related to sleep-related respiratory disturbances in these patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Severe community-acquired pneumonia. Etiology, epidemiology, and prognosis factors. French Study Group for Community-Acquired Pneumonia in the Intensive Care Unit.

A prospective study of 132 patients with severe community-acquired pneumonia (CAP) treated in the ICU was carried out to determine the causative agents, the value of the clinical, biological, and radiologic features in predicting the etiology, and to define prognostic factors. The study group included 98 men and 34 women (mean age: 58 +/- 18 years). The most frequent underlying condition was COPD (51 patients, 39 percent). On admission, 35 patients were in shock, 71 were mentally confused, and 81 (61 percent) required mechanical ventilation during their hospitalization. The clinical, laboratory, and radiologic parameters were of little value for predicting the etiology in patients with severe CAP. An etiologic diagnosis was made in 95 (72 percent) patients. The most frequent pathogens were Streptococcus pneumoniae (43 cases [45 percent]), Gram-negative bacilli (14 cases [15 percent]), and Haemophilus influenzae (14 cases [15 percent]) Mortality was 24 percent. It was significantly associated with a age more than 60 years, septic shock, impairment of alertness, mechanical ventilation requirement, bacteremic pneumonia, and S pneumoniae or Enterobacteriaceae as the causes of the pneumonia. Recommendations for antibiotic chemotherapy in patients with severe CAP admitted to the ICU are included.

Community-Acquired Infections↗

Intravenous immune globulin in myasthenia gravis.

Myasthenia gravis (MG) is an autoimmune disease of neuromuscular transmission associated with the presence of anti-acetylcholine receptor antibodies (anti-AChR Ab). Current treatment of MG includes anti-cholinesterase drugs, thymectomy, corticosteroids, immunosuppressants and plasma exchange (PE). The use of intravenous immune globulin (IVIG) in MG was proposed 10 years ago. Published results of IVIG treatment are discussed and the need for a controlled study is emphasized.

Autoantibodies↗