Biomedical subjects
Publications and source records attributed to A Robert.
Two siblings and two other unrelated patients had congenital muscular weakness and dystrophic changes but normal immunocytochemical stainings for merosin, dystrophin, and dystrophin-related proteins on muscle biopsy. All had marked ataxia and cerebellar atrophy or hypoplasia. Cerebral white matter and cortical organization appeared normal.
BACKGROUND: Cigarette smoking is the cardinal cause of COPD, but only a relatively small percentage of smokers have development of clinically overt disease. OBJECTIVES: To identify high-risk subjects and to assess the prognostic significance of "small airways" tests. SETTING: University teaching hospital. SUBJECTS: Fifty-six smokers and ex-smokers of mean age 62.5 years (SD, 2.7) with a smoking history of 40.6 (18.9) pack-years were studied at the end of a 13-year follow-up period. MEASUREMENTS: Questionnaire and lung function tests, including static and dynamic lung volumes, airway resistance, maximal expiratory flow rates, and small airways tests, such as nitrogen slope of the alveolar plateau (N2 slope) and closing volume. RESULTS: Eighty-two percent of subjects with a normal FEV1/vital capacity (VC) ratio at the start of the study (half of them with abnormal results of small airways tests) still had a normal FEV1/VC ratio 13 years later. In the remainder, all but one had final FEV1/VC values >60%. About 80% of subjects with a decreased FEV1/VC at the start (subjects with airflow obstruction) reached at the end of study lower than predicted FEV1/VC values. Only about 10% of these subjects showed an accelerated loss of FEV1, reaching end FEV1/VC values of <45%. Initial N2 slope predicted about 80% of end FEV1 values. CONCLUSION: Middle-aged smokers are at no evident risk of functional deterioration if their FEV1/VC ratio is normal. This is so even if results of small airways tests are abnormal. A decreased FEV1/VC ratio has no serious implications in itself. Only an associated high N2 slope adds the necessary information to predict a low FEV1. Present data suggest that a subgroup of smokers in their 50s, characterized by a low FEV1/VC ratio and a high N2 slope, are probably the susceptible smokers at high risk for development of COPD.
Changes in membrane potential of both axons and Schwann cells were measured simultaneously during electrical activity and during the period of recovery in the rabbit vagus nerve by the use of the sucrose-gap apparatus. During low-frequency stimulation (0.5-1 Hz) the preparation developed a ouabain-sensitive hyperpolarization. This hyperpolarization increased when the inwardly rectifying K+ channels in Schwann cells were blocked with Ba2+, indicating that the hyperpolarization was generated by the electrogenic glial Na(+)-K+ pump. During trains at higher frequencies (15 Hz), the preparation depolarized, but after cessation of the stimulation it developed a posttetanic hyperpolarization (PTH). The PTH was also ouabain-sensitive and was strongly enhanced by Cs+ which is known to block the hyperpolarization-activated inward current (Ih) in axons but not in glial cells. These results show that the PTH reflects mainly the axonal electrogenic pump. Our results indicate that during activity the K+ released from the firing axons is removed from the extracellular space by Schwann cells and that after cessation of the stimulation the K+ surplus returns from Schwann cells back to axons. Both the glial and axonal K+ uptake is mediated by successive activation of the glial and axonal Na(+)-K+ pump. The nature of the signalling mechanisms that control the pumping rates of the respective pumps remain unknown.
The recommended therapeutic range of International Normalized Ratio (INR) for oral anticoagulant treatment in patients with the antiphospholipid syndrome remains controversial. As a part of this controversy, it has been suggested that lupus anticoagulants (LA) could interfere with the determination of prothrombin time, thus questioning the validity of monitoring the treatment of these patients using INR. To clarify this point, we compared the values of INR obtained in the plasmas of two groups of patients, one without LA (n = 47), and the other with LA (n = 43). INR were determined using 8 different thromboplastin reagents on the same automated coagulation instrument. Chromogenic factor X, which is supposed to be insensitive to the presence of LA, was also measured. The results are the following: provided INR was calculated using calibrated reference plasmas, there was no significant difference between INR values obtained with the 8 reagents, both in the non-LA and in the LA groups (CV: 5.9 and 6.7%. respectively). Closer examination revealed that INR results obtained with one reagent (the recombinant thromboplastin Innovin) diverged from those of the 7 others, leading to an overestimation of INR, to a very large extent in some instances. However this effect was restricted to a subset of the patient population with LA (6 out of 43). Finally, the relationship between INR (average value obtained using the 8 reagents) and factor X was identical in non-LA and in LA patient groups. We conclude that, provided the reagents which display the LA interference are identified and excluded for this purpose, the INR system is valid for monitoring oral anticoagulant treatment in patients with LA.
We have shown that administration of inorganic potassium phosphates (Pi) to patients with severe diabetic ketoacidosis was able to increase the P50 (the PO2 necessary to achieve a hemoglobin saturation of 50%) by a non diphosphoglycerate (DPG) mediated effect. This suggests that the oxyhemoglobin dissociation curve (ODC) may be determined not only by pH, temperature, CO2 content and DPG but also by plasmatic ions. In order to test this hypothesis we have determined the ODC on whole blood in two groups of subjects, 49 control subjects with matching age and sex and 49 patients suffering from liver cirrhosis, acute pancreatitis, septic shock and acute respiratory distress syndrome. The patients had many ionic disorders induced either by their diseases or by the applied treatment. The mean ODC of the patients did not differ from the normal values. In contrast, the dispersion of PO2 around the saturations values was increased from 5 to 80% saturation. A forward regression analysis showed that the DPG level and the levels of inorganic phosphates and natrium (Na+) played a significant role in determining the position of the ODC according to the following equation: P50 (mmHg) = 34.5 + 0.225 DPG + 0.62 Pi-0.09 Na+, where DPG is in micromol.gHb-1 and Pi and Na+ in mEq.l-1. In separate experiments we showed that the Bohr effect as expressed in d (log PO2)/dpH amounted to -0.53, -0.46 and -0.42 for SO2 equal to 5%, 50% and 95%, respectively. The corresponding values for the temperature effect was expressed in d (log PO2)/dT amounted to 0.028, 0.024, and 0.020 respectively. The fact that ions play an role in regulating the position of the ODC of patients with ionic disorders may have therapeutical implications, preventive or curative.
The multiple inert gas elimination technique (MIGET) is being increasingly used in respiratory physiology and pathophysiology. Six inert gases are given as an intravenous infusion then measured in samples of expired air and mixed arterial and venous blood. This requires right-sided catheterization, a procedure that is sometimes ethically inappropriate. The present article reports a method in which inert gas levels in mixed venous blood were calculated, rather than measured, using Fick's law. Echocardiography was used to measure arterial inert gas levels and cardiac output. The method was validated in 11 men scheduled to undergo coronary bypass surgery. Cardiac output was either calculated based on biometrical (C) data or measured using four different methods in random order, namely Fick's law with oxygen (FiO2) or the inert gases (FiIG) as the tracers, thermodilution (TH), and echocardiography (E). Cardiac output values in L.min-1 (mean +/- SD) were as follows: C, 4.99 +/- 0.39; FiO2, 5.44 +/- 0.86; FiIG, 5.55 +/- 0.92; TH, 5.77 +/- 0.88; and E, 5.53 +/- 0.64. No significant differences were found among the four measured cardiac output values, of which the mean was 5.57 +/- 0.70 L/min, a value that was significantly higher than the calculated value. This difference is probably ascribable to the use of dopamine, dobutamine, or epinephrine in six of the 11 patients. A 1 L/min-1 cardiac output error, in either direction, was found to have a marked influence on the distribution of alveolar perfusion at various VA/Q ratios. Conversely, as expected, ventilation distribution was not influenced by cardiac output. In conclusion, echocardiography provides satisfactory cardiac output estimations using the MIGET except in patients with septal hypertrophy, subaortic membranes, a mitral valve prosthesis, or a mitral valve ring.
Monoclonal antibodies used to distinguish between dystrophin and utrophin were systematically applied to skeletal muscles containing arteries and veins. Small arteries were found to contain long forms of both utrophin and dystrophin, while small veins contained only long forms of utrophin. In addition, all sizes of vascular smooth muscles were demonstrated to contain another related Mr 80 kDa protein (possibly a short utrophin transcript). Regardless of their tissue distributions, we assumed that each of these molecules had distinct properties, i.e. dystrophin with a mechanical function and utrophin with an architectural function. This difference in the roles of dystrophin and utrophin could reduce the efficiency of protection against muscle membrane degeneration when utrophin overexpression is programmed.
A subunit approach to the development of a respiratory syncytial virus (RSV) vaccine was investigated. It involved the production, in Escherichia coli, of an RSV (Long) G protein fragment (G2Na) as a C-terminal fusion partner to an albumin binding region (BB) of streptococcal protein G. G2Na incorporated amino acid residues 130-230 and was specifically recognized by murine anti-RSV-A polyclonal serum. In mice, intraperitoneal immunization with BBG2Na induced high anti-RSV-A serum ELISA titers and low to moderate neutralization activity. The immune response induced by BBG2Na demonstrated a potent protective efficacy against upper and lower respiratory tract RSV-A infection. The immunogenicity and protective efficacy of BBG2Na was maintained for at least 47 and 48 weeks, respectively, and was as potent and durable as live RSV-A administered in a similar fashion. Intramuscular immunization of cotton rats with BBG2Na protected lungs from both homologous and heterologous virus challenge. In contrast to mice, however, cotton rat nasal tracts were not protected after BBG2Na immunization. Consistent with antibody-mediated protection, virus was cleared within 24 hr from the lungs of BBG2Na-immunized mice. The anti-RSV-A antibodies induced in mice were exclusively of the IgG1 isotype and were detected in the serum, lungs, and nasal tracts. Passive transfer of these antibodies prevented acute, and eliminated chronic, RSV-A lung infection in normal and immunodeficient mice, respectively, confirming that such antibodies are important and sufficient for BBG2Na-induced pulmonary protection. Our results clearly demonstrate that BBG2Na contains an important immunogenic domain of the RSV G protein. The prokaryotic origin of this protein indicates that glycosylation of the RSV G protein is not necessary for protective efficacy. Thus, BBG2Na has potential as an RSV subunit vaccine.
As an attempt to better understand the metabolic basis for the previously reported increases in glucose metabolism in the visual cortex of congenitally blind subjects, cerebral blood flow, oxygen consumption and glucose utilization were investigated with multitracer positron emission tomography. Measurements were carried out in three subjects who became blind early in life and in three age-matched blindfolded controls. Regional analysis of cerebral blood flow, metabolic rates for oxygen and glucose utilization revealed that these parameters were relatively higher in the visual cortex in case of early blindness (109.7 +/- 2.4%; 114.3 +/- 1.5%; 118.0 +/- 5.5%, respectively) than in controls (98.1 +/- 3.9%; 108.6 +/- 3.6%; 105.2 +/- 4.8%). There were slight differences, albeit statistically not significant, between early blind and control subjects in terms of oxygen-to-glucose metabolic ratios. The relatively preserved stoichiometry in the visual areas of blind subjects points to the lack of variation in the yield of glucose oxidation in this cortex. Those observations suggest that the high level of energy metabolism disclosed in early blind visual cortex is related to neural activity.
Since capillaries appear not to contribute significantly to rapid removal of K+ from brain tissue, the K+ released into extracellular clefts by neurons at the onset of electrical activity is presumably removed either by redistribution in the clefts or by uptake into cells. What appear to be the three major processes require no energy from the glial cells. These are diffusion through the extracellular clefts, spatial buffering by glial cells, and net uptake of K+ into glial cells through glial K+ channels associated with uptake of Cl- through an independent Cl- conductance. There is a relatively slow uptake by the Na+/K+-ATPase, which directly consumes ATP. In addition, some glial cells take up K+ on the Na+/K+/2Cl- cotransporter, which leads indirectly to energy consumption when the Na+ is subsequently pumped out. Currently available data suggest that the glial energy metabolism devoted to K+ homeostasis is less than a tenth of the total tissue energy metabolism, even under conditions of pathologically high extracellular [K+]. Hence, in situ, it is possible that glial cells could function with much less ATP than neurons do. All the various routes of muffling of changes in extracellular [K+] can be modulated, directly or indirectly, by transmitters liberated by neurons. A consequence of this could be regulation of the entry of Na+ into glial cells such that the Na+/K+-ATPase is activated. The degree of activation might be adjusted so that the resulting activation of the glial glycolytic pathway is appropriate to the provision of the quantity of metabolic substrates required by the neurons.
Explore the source record for details and available documents.
By comparison with localizations of dystrophin family products in rabbit peripheral nerves, we investigated the potential existence and distribution of similar products in peripheral nerves from Torpedo marmorata. In immunofluorescence studies, a specific set of monoclonal antibodies directed against dystrophin family proteins clearly stained a thin rim surrounding each Schwann cell-axon unit both in T. marmorata and rabbit peripheral nerves. In contrast when using the dystrophin/utrophin monoclonal H'3E7 antibody, we found a clear difference between rabbit and T. marmorata peripheral nerves according to fluorescent labeling detected within Torpedo nerve axons. Further differences were noted following western blot analyses of T. marmorata peripheral nerve extracts, highlighting the presence of a new and specific M(r) 70-kDa protein band belonging to the dystrophin family, which is localized within axons in addition to: (1) an M(r)400-kDa protein band detected with dystrophin/utrophin antibodies; and (2) an M(r) 116-kDa doublet protein band corresponding to Dp116 and Up116 isoforms. All of these products, detected according to the specificities of the monoclonal antibodies used, are discussed in terms of their potential identities as short and long dystrophin or utrophin mammalian products.
BACKGROUND: In adults, competition generates a relatively important level of stress. This could be revealed by psychological questionnaires and adrenocortical responses. This study was aimed to evaluate the load of stress in young tennis players in situations of competition compared to that observed during a training session. POPULATION AND METHODS: The 16 best young tennis players of the Auvergne area (mean age: 10.9 +/- 1.7 years) entered the study. The degree of anxiety was measured with the aid of the Martens' SCAT questionnaire and the result of salivary cortisol testing during a training session, and after each of the three competition rounds of the Auvergne championship (three samples were collected at each time: at rest, before and after exercise. RESULTS: Regarding the degree of anxiety, no significant difference was found between the competition and the training session. Cortisol levels did not change during the training session: during the competition, same moderate increase (less than 50%, P < 0.05) was noted for the first two rounds between rest and post-competition values. No difference was found at the third round. CONCLUSION: The high levels of stress described in adults are not found in young tennis players.
Burn injury is considered by children as one of the most painful traumas (just after bone factures). Burn pain in children can and must be controlled as well as for adult patients, with almost identical techniques. Continuous pain from injury and intermittent pain caused by therapeutic procedures must be evaluated and treated separately. Due to very high levels of nociception, satisfactory management of procedural pain requires the use of opioid therapy. Non pharmacological methods are meaningless if pharmacological treatment is not optimal.
We report two infants with acute basophilic leukaemia associated with a t(X;6)(p11;q23) as the sole abnormality. Morphologic evidence of basophilic lineage was provided by light and electron microscopy. Both patients also had a similar presentation on diagnosis, characterized by clinical signs consistent with a hyperhistaminaemia syndrome, i.e. urticarian rashes and gastro-intestinal disorders evocative of peptic ulcer. Immunophenotypes differed in the two patients, one expressing CD24, CD13 and CD33, whereas only CD117 was found in the other. Basophilic acute leukaemia, a rare group among acute leukaemias, might be nonrandomly associated with a specific chromosomal abnormality, t(X;6)(p11;q23). This new entity might also be identifiable by an uncommon clinical presentation and occurrence in infancy.
The accumulation of hydroxyethyl starches (HES) in monocytes/macrophages has raised concern over their potential detrimental effects on host defences. We assessed prospectively the function of circulating monocytes isolated from patients treated with plasma exchange (PE) using HES. The study was carried out in the medical intensive care unit of a university hospital. Eight patients underwent PE for neurological disorders. Each patient underwent three PEs, 48 h apart. The total exchange volume was 4 L per PE. Only 4% human albumin was used for the first PE. In the second and third PEs, the plasma substitute was 2 L of HES (200,000/6%/0.62) and 2 L of albumin. Mononuclear cells were collected before and immediately after each PE and 48 h after the last PE. They were placed in suspension culture and incubated with lipopolysaccharide (LPS). Monocyte function was assessed in terms of procoagulant activity (PCA) and tumour necrosis factor alpha (TNF-alpha) production. LPS-stimulated PCA increased after the first PE (P < 0.05). Stimulated TNF-alpha production increased, but not significantly so. Similar effects were observed after the second and third PE (P < 0.05 for stimulated TNF-alpha). Values 48 h after the last PE were similar to those obtained before the second PE, suggesting that repeated infusions of HES had no detrimental effect on monocyte function. Furthermore, plasma oncotic pressure was preserved after PE with HES. These results support the partial replacement of costly human albumin with HES during repetitive PE, and suggest that HES might be a safe plasma expander in septic patients.
Using the microparticle capture enzyme-immunoassay (MEIA) based on IMx technology (Abbott), we determined the current prevalence of toxoplasmosis in 784 pregnant women followed up during 1990, and in 1,839 randomly selected blood donors. They all came from the Brabant Wallon area and the South-East of Brussels. Specimens yielding low IgG immunity (6-15 units) [corrected], were further tested with a sensitive direct agglutination assay (Toxo-Screen DA, bioMerieux). Overall, the prevalence was 67% among blood donors and 50% in pregnant women. In blood donors, the prevalence in women was not statistically different from the prevalence in men: X2 = 2.95 NS. In the two populations, a progressive age-related increasing prevalence of up to 60% for pregnant women and 77% for blood donors was observed. In females, the prevalence was higher among female blood donors than among pregnant women: 63% versus 50%, X2 = 16, P < 0.001. However, when the prevalences were compared within three age subgroups of women (< or = 33 yrs, 34 to 41 yrs, > or = 42 yrs), there were no statistically significant differences between pregnant women and blood donors. Thus, the overall observed difference was due to an age effect. Therefore, the distribution of IgG titers was established in each of the six age and sex subgroups. The 25th, 50th and 75th percentiles of those distributions ranged between 14 IU and 20 IU, 24 IU and 35 IU, and 40 IU and 64 IU, respectively. The annual seroconversion rate was 0.8% in pregnant women, against 0.2% amongst non-immune blood donors over 3 months. In conclusion, our findings confirm the general prevalence of 50% of toxoplasmosis and an annual seroconversion rate of 0.8% in these two populations.
OBJECTIVE: Increased dispersion of ventricular repolarization has been shown to be a marker for increased risk of ventricular tachyarrhythmias in various cardiac disorders. The present study is aimed at comparing the values of four dispersion indices in four clinical groups: normal subjects (n = 23), patients with intraventricular conduction defects (QRS > 0.12 s) without underlying cardiac disease (n = 30), patients with dilated cardiomyopathy (n = 36), and patients with both dilated cardiomyopathy and ventricular conduction defects (n = 18). METHODS: On an averaged cycle from a 10 s record of 15 simultaneous leads (12-lead ECG and XYZ leads), and after interactive editing, four intervals were computed: JTapex, JTend, QTapex and QTend. For each interval, the dispersion is defined as the difference between the maximal and minimal values across the 15 leads. RESULTS: The mean values of all four dispersion indices were significantly smaller in the normal group than in the three other groups (P < 0.001). Among patients with dilated cardiomyopathy, those with intraventricular conduction defects had significantly higher dispersion values than those without, even disregarding the QRS duration (P < 0.01). Thus, patients with both dilated cardiomyopathy and ventricular conduction defects have larger dispersion values than patients with ventricular conduction defects alone (P < 0.01) and than those with dilated cardiomyopathy without intraventricular conduction defects. CONCLUSION: Dispersion of ventricular repolarization is increased in patients with dilated cardiomyopathy, especially in those with ventricular conduction defects, suggesting that they are at higher risk of arrhythmic events.