Dramatic impact of morbid obesity on child lung development.

OBJECTIVE: To assess the respiratory function and sleep characteristics of obese adults and children. METHODS: All patients with non-syndromic, severe obesity (BMI ≥3 z-scores for children and ≥40.00kg/m2 for adults), referred for pulmonary function tests at Lille University Hospital, were retrospectively included. RESULTS: A total of 69 children (mean±SD BMI 36.8±6.7 and mean BMI z-score 4.7±1.0) and 70 adults were included (mean BMI 45.7±6.2). Metabolic syndrome was diagnosed in 13 children (26%) and 40 adults (80%). Reduced lung volumes were observed in 34 children (50.0%) and 16 adults (24.0%) and both the mean functional residual capacity (FRC) and the mean residual volume (RV) were lower in children than in adults (FRC: -1.7±2.1 z-score in children vs. -1.0±1.1 in adults, P=0.026; and RV: -0.8±1.2 z-score in children vs. -0.1±1.1 in adults, P=0.002). The prevalence of severe obstructive sleep apnea syndrome was greater in adults (40.7% vs. 18.8%, P=0.007). Children had a higher average oxygen saturation (median of 96.0% [91.0-98.0] vs. 93.0% [76.0-97.0] in adults, P<0.0001). CONCLUSION: Obesity has consequences for lung volumes in children; however, a longitudinal study is needed to determine the impact on pulmonary expansion and growth.

[Effects of an educational program in non-adherent apneic patients treated with continuous positive airway pressure]. / Éducation thérapeutique de patients apnéiques inobservants sous pression positive continue.

INTRODUCTION: Obstructive Sleep Apnea (OSA) is a chronic, frequent pathology impacting patients' quality of life. Continuous positive airways pressure (CPAP) is the most effective treatment, but is often considered binding and thus poorly observed. The aim of this study was to assess the impact of an educational program in non-adherent patients with OSA, to identify the factors of inobservance and to determine risk groups. PATIENTS AND METHODS: We enrolled 21 patients presenting OSA in this monocentric, forward-looking study. Nineteen patients completed the study. The inclusion criterion was a daily observance less than 4 hours a night. Educational program was realized by a specialized, trained team, with the authorization of the Regional Agency of Health. RESULTS: Our population consisted of 15 male and six female, all of them obese, with a medium age of 57.7 ± 12.9 years, treated for 10,7 ± 15 months. All of our patients had few symptoms. After the educational program, two groups were individualized according to their observance. Fifty-two percent of patients became compliant to CPAP treatment. Demographic data and medical histories did not differ between these two groups: nine patients remained inobservant (medium daily treatment duration of 57 ± 49 minutes); ten patients became observant (medium daily treatment duration raising from 104 ± 70 minutes to 322 ± 65 minutes, P=0.0002). Among these ten patients, seven were considered as having accepted their disease at initial educational diagnosis. CONCLUSION: The educational program improved adherence to CPAP treatment in 52% of our patients. All included patients had few symptoms. This could raise the issue of a poorer perception of treatment efficacy in less symptomatic patients. Disease acceptance also appeared linked to CPAP treatment compliance.

[Idiopathic pulmonary fibrosis and sleep disorders]. / Fibrose pulmonaire idiopathique et troubles du sommeil.

Idiopathic pulmonary fibrosis (IPF) is the most common interstitial lung disease. Despite progress made in understanding the pathophysiological mechanisms behind the development of the disease, its prognosis is poor. For this reason, any measure to improve the quality of life for these patients should be preferred. Some authors are interested in sleep disorders, and possible impact on quality of life. Patients with IPF have lowered scores of quality of life compared to those found in general population, with some correlation with the scores of sleep quality. There is a hyperfragmentation with many arousals and desaturation events. Some authors also report an apnea-hypopnea index higher in these patients, but these data are not found in all the studies. Correcting these obstructive phenomena may have a beneficial effect on survival, which would make systematic the sleep assessment in these patients. Finally, the relationship between IPF, gastroesophageal reflux and sleep apnea syndrome remains unclear.

Prevalence of residual excessive sleepiness in CPAP-treated sleep apnoea patients: the French multicentre study.

The percentage of compliant continuous positive airway pressure (CPAP)-treated apnoeic patients that continue to experience residual excessive sleepiness (RES) is unknown. RES was defined by an Epworth Sleepiness Scale (ESS) score of >or=11. In total, 502 patients from 37 French sleep centres using CPAP >3 h night(-1) attending their 1-yr follow-up visit were eligible. ESS and polysomnographic data as well as symptoms, quality of life, depression scores and objective CPAP compliance at 1 yr were collected. Overall, 60 patients remained sleepy on CPAP (ESS 14.3+/-2.5) leading to a prevalence rate of RES of 12.0% (95% confidence interval (CI) 9.1-14.8). After having excluded associated restless leg syndrome, major depressive disorder and narcolepsy as confounding causes, the final prevalence rate of RES was 6.0% (95% CI 3.9-8.01). Patients with RES were younger and more sleepy at diagnosis. The relative risk of having RES was 5.3 (95% CI 1.6-22.1), when ESS before treatment was >or=11. Scores of emotional and energy Nottingham Health Profile domains were two times worse in patients with RES. As 230,000 obstructive sleep apnoea patients are currently treated in France by continuous positive airway pressure, more than 13,800 of them might suffer from residual excessive sleepiness.

Physiologic correlates of dyspnea in patients with morbid obesity.

OBJECTIVE: Mechanisms of dyspnea in obesity remain unclear. This study was undertaken to determine the relationships between dyspnea and pulmonary function including inspiratory muscle endurance (IME) in morbidly obese patients before bariatric surgery. RESEARCH METHODS AND PROCEDURES: Fifty-five patients with a mean+/-s.d. body mass index (BMI) of 49.4+/-7.0 kg/m(2) were included. Dyspnea was evaluated by the Baseline Dyspnea Index (BDI; 0-12, 0=maximal dyspnea). Pulmonary function tests included a plethysmography, maximal inspiratory pressure (PImax) and IME was assessed by the incremental threshold loading test, determining the maximal pressure sustained for 2 min (Plim(2)) and Plim(2)/PImax ratio. Patients were classified according to their BMI in two groups: BMI < or =49 (n=27) and >49 kg/m(2) (n=28). RESULTS: Breathlessness was higher in the BMI >49 kg/m(2) group compared to the BMI < or =49 kg/m(2) group (BDI score at 6.9+/-2.2 in the BMI >49 kg/m(2) group vs 8.9+/-2.5 in the BMI < or =49 kg/m(2) group, P<0.01). Patients with BMI >49 kg/m(2) had significantly higher PaCO(2) level and significantly lower vital capacity, inspiratory capacity and PImax values compared with the BMI < or =49 kg/m(2) group. Correlations between BDI and lung function were moderate: forced expiratory volume in 1 s (FEV(1))% pred: Rho=0.27; P=0.05; vital capacity % pred: Rho=0.40; P=0.004; and Plim(2)/PImax: Rho=0.40; P=0.003. Higher correlations with dyspnea were found in the BMI < or =49 kg/m(2) group: FEV(1)% pred: Rho=0.38; P=0.05; and Plim(2)/PImax: Rho=0.49; P=0.01. DISCUSSION: Inspiratory muscle performance is moderately reduced in morbid obesity. Dyspnea in these patients remains moderately related to lung function and inspiratory muscle performance. However, inspiratory muscles performance correlates more significantly with dyspnea in patients with a BMI < or =49 kg/m(2).

[Radiographic anomalies and obstructive sleep apnea syndrome]. / Anomalies téléradiographiques et syndrome d'apnées obstructives du sommeil.

BACKGROUND: The purpose of this study was to identify the particular cranio-facial pattern observed in patients with obstructive sleep apnea syndrome and to search for possible correlations between morphological anomalies and disease severity. MATERIAL AND METHODS: The study group included 49 dentate patients, mean age 47.7 years suffering from obstructive sleep apnea syndrome. Most of the patients were overweight. RESULTS: Typical features observed in these patients were a short craniospinal field, a retro-maxillary, a retro-mandibula, antero-inferior vertical excess of the face, and class II malocclusion. No correlation between severity of obstructive sleep apnea syndrome and craniofacial morphology could be identified. DISCUSSION: These results are in agreement with data in the literature. The absence of a morphological correlation appears to be related to the type of patients studied (overweight). Indeed, two categories of sleep apnea patients have been identified: obese patients who have few or no anomalies of the facial skeleton and thin patients with characteristic open bite class II malocclusion.

[A rare cause of chronic respiratory insufficiency: arthrogryposis in adults]. / Une cause rare d'insuffisance respiratoire chronique: l'adulte.

Arthrogryposis is a congenital disease leading to multiple joint ankylosis in utero observed as sequellae at birth. Deformation of the chest produces respiratory failure usually seen at birth. We report a case in an adult which required intermittent nocturnal positive pressure nasal ventilation.

Modulation of type A K+ current in Drosophila larval muscle by internal Ca2+; effects of the overexpression of frequenin.

The calcium-dependent modulation of type A K+ current (IA) has been investigated using a two-electrode voltage clamp on larval muscle cells of Drosophila. It was found that the amplitude of IA increases when [Ca2+]o is changed from 0.2 mM to 2 mM. The increase in IA amplitude is not due to overlap with the Ca(2+)-dependent fast K+ current, ICF, since it is observed also in slo1 mutants, which are deficient for this current. This effect is not due to Ca(2+)-dependent shifts in the steady-state activation/inactivation kinetics. The phenomenon is probably due to elevations in internal calcium since it is abolished by Ca2+ channel blockers and promoted by caffeine (5 mM) if added in the absence of external calcium. This calcium effect was dose-dependent since it was not observed in the presence caffeine plus 2 mM calcium in the bath nor for values of [Ca2+]o above 4 mM. The Ca(2+)-dependent modulation of IA is absent in V7, a mutation that causes overexpression of frequenin, a recoverin-like Ca(2+)-binding protein which stimulates guanylyl cyclase [31]. One possible explanation for the loss of IA modulation in the V7 mutation is that the excess of frequenin alters intracellular cGMP-dependent metabolic pathways responsible for the internal calcium homeostasis.

[Surgical treatment of snoring and sleep apnea syndromes. Results apropos of 59 cases]. / Traitement chirurgical du ronflement et des apnées du sommeil. Résultats à propos de 59 patients.

From 1991 to 1993, 59 patients underwent surgical cure for snoring. Polysomnography was performed 47 times when history taking and clinical signs revealed diurnal and nocturnal manifestations. Sleep apnea was confirmed in 20 patients with a mean apnea-hypnea index of 34.1. Treatment was based on surgery of the velum palatinum in 59% of the cases, the palatine tonsils in 39% and the basilingual tonsils in 1 patient. Snoring disappeared in 24 patients (40%) and improved for 75% satisfaction in 22 patients (37%).

Implication of frequenin in the facilitation of transmitter release in Drosophila.

1. We have investigated the possible role of frequenin in the modulation of synaptic facilitation at the larval Drosophila neuromuscular junctions. Excitatory junctional currents (EJCs) and presynaptic nerve terminal currents were recorded by external electrodes in normal larvae and in transgenic larvae carrying an extra insertion of the frequenin cDNA. 2. Motor nerve stimulation by twin pulses or trains of stimuli provoked EJC facilitation which was about three times higher in transgenic larvae compared to controls. Unconditioned EJCs revealed, however, similar quantal content and Ca2+ sensitivity in both Drosophila strains. 3. Differences between normal and transgenic Drosophila in the quantal content of the facilitated EJC do not depend on differences in the duration of the repolarization phase of the presynaptic action potential. 4. Perfusion of tetrodotoxin or of low-Na+ solutions abolished the enhancement of the EJC facilitation observed in the transformants. These treatments only slightly affected the facilitation of normal junctions. 5. These results suggest that (i) internal Na+ accumulation can enhance facilitation of transmitter release in Drosophila neuromuscular junctions overexpressing frequenin, and (ii) this effect possibly depends on a modulation of the activity of the Na(+)-Ca2+ exchanger by frequenin.

Calcium-dependent modulation of the facilitation of transmitter release at neuromuscular junctions of Drosophila.

The relationship between external Ca and twin pulse facilitation of transmitter release has been investigated in neuromuscular junctions of Drosophila larvae using external electrodes to record excitatory junctional currents (ejcs). The degree of synaptic facilitation decreases in inverse relation to [Ca2+]0, even at levels of transmitter release that do not cause depletion of quanta. This reverse-dependency of facilitation to external calcium is abolished by the slow mutation which suppresses the transient Ca-dependent K current (ICF). A likely explanation for these observations is that the activation of ICF by residual Ca shortens the action potential duration resulting in a reduced release of transmitter to the test stimulus. This represents a negative feed-back mechanism of synaptic function which opposes synaptic facilitation.

Nerve terminal excitability and neuromuscular transmission in T(X;Y)V7 and Shaker mutants of Drosophila melanogaster.

We investigated the neuromuscular transmission in relation with genetic neuronal excitability changes in mutants T(X;Y)V7 and ShK,S133 of Drosophila. These mutations affect two different genes belonging to the Shaker gene complex which encode different yet functionally related proteins. Experiments were performed on neuromuscular junctions from Drosophila larvae by recording pre- and postsynaptic membrane currents using external electrodes. It was found that the neuromuscular electrophysiological phenotype of T(X;Y)V7 is caused by presynaptic membrane hyperexcitability probably in relation with a Ca2(+)-dependent down regulation of voltage dependent K channels. By contrast, the ShKS133 phenotype can be explained solely by action potential widening due to the absence of type-A K channels.

Presynaptic actions of botulinal neurotoxins at vertebrate neuromuscular junctions.

1. In the present paper we review some presynaptic aspects of the mode of action of botulinal toxins (BoTxs) at vertebrate neuromuscular junctions with emphasis on studies carried out in our laboratories using electrophysiological and morphological techniques. 2. Spontaneous quantal transmitter release recorded as miniature end-plate potentials is drastically affected by BoTxs. The low probability of release at poisoned terminals can be enhanced by carbonyl cyanide m-chlorophenylhydrazone (CCCP), Cd2+ and La3+. However, CCCP and La3+ which drastically deplete clear synaptic vesicles from unpoisoned terminals failed to markedly affect the density of synaptic vesicles at poisoned terminals. It is concluded that poisoned terminals have a reduced sensitivity to the release-promoting action of Ca2+, Cd2+ and La3+. 3. When comparing the effect of the various BoTxs on nerve-impulse evoked transmitter release it appears that increasing phasic Ca2+ entry into the terminals enhances evoked synchronized quantal release only from terminals poisoned with serotypes A and E. In contrast, enhanced Ca2+ entry into terminals poisoned with serotypes B, D and F induced a period of high frequency asynchronous release suggesting that these BoTxs may affect a presynaptic step beyond the influx of Ca2+, that may be involved in the synchronization of transmitter quanta. These data suggest that the actions of BoTxs involve several steps of the acetylcholine release process. 4. The analysis of presynaptic currents which depend on both Ca2+ entry and intraterminal background Ca2+ levels strongly suggests that neither Ca2+ entry nor intraterminal Ca2+ levels are altered by BoTxs. Furthermore, poisoned terminals are no more efficient than unpoisoned ones in dealing with Ca2+ overloads. 5. Finally, the morphological examination of junctions paralysed by BoTx-A indicates that the toxin triggers a particularly important overgrowth of the nerve terminals and suggests that the in vivo functional recovery may occur from an extension of the original nerve terminal arborization and the concomitant remodelling of postsynaptic structures.

[Amoxicillin as a 1st choice: 275 acute focal pneumopathies treated on an outpatient basis]. / Amoxicilline en première intention: 275 pneumopathies aiguës en foyer traitées en ville.

From December 1986 to January 1988, 100 General Practitioners and Pneumologists working outside hospital included in open unmatched series 275 patients who were diagnosed as having pneumonia at home. The study consisted of 53.2% men with an average age of 49.3 plus or minus 19.3. Their temperature on the first day (J1) was in 72.7% of cases greater than 38.5 degrees Centigrade. The doctors felt that the general state was good in 66.5% of the cases. Cough was present in 83.5% of cases but was dry in one out of every two. The patients received Amoxycillin in a dose of 2 grams per day orally (66.9%), or by injection (33.1%). On the third day (J3) 90% of the patients had a temperature below 38.5 degrees Centigrade. Their general state was improved in 94.6% of cases. The diagnosis of pneumonia at home was confirmed radiologically on 219 of the films available, confirming the good specificity of the clinical diagnosis of pneumonia at home. Ten patients were hospitalised. The apparent treatment of Amoxycillin was given in 247 cases (89.8% of cases). In 28 cases (10.2%) the treatment was changed by the addition or substitution of a Macrolide (15), or another antibiotic (5), and in 80 cases a change of treatment was not specified. 25 of these 28 cases were reviewed on the 14th day (J14) and no failures were observed after the change of treatment. In 247 patients in whom the treatment with Amoxycillin was followed 336 were reviewed on the 15th day and there had been four failures. Three were intolerant to the drug and there was one relapse.(ABSTRACT TRUNCATED AT 250 WORDS)

Presynaptic calcium currents recorded from calyciform nerve terminals in the lizard ciliary ganglion.

Electron microscopic examination of ciliary ganglion from Anolis carolinensis shows large calyciform presynaptic nerve terminals ending on ganglion cells. Intracellular records were obtained from the terminals, and membrane currents were recorded with the single-electrode voltage clamp technique. After block of Na+ currents with tetrodotoxin, depolarization of the terminals produced inward currents that disappeared when extracellular Ca2+ was removed, and increased in magnitude and duration when competing outward currents were blocked by intracellular Cs+. Thus it is possible, with this preparation, to record and characterize Ca2+ currents presumably associated with neurotransmitter release.

Membrane currents in lizard motor nerve terminals and nodes of Ranvier.

Presynaptic membrane currents were recorded by external electrodes and nodal membrane currents were obtained by the voltage clamp technique in motor nerve endings and nodes of Ranvier of the lizard Anolis carolinensis. Although of compact shape, lizard motor endings display relatively long terminal branches; they exhibit, in agreement with previous findings in mouse and frog motor terminals, Na, Ca and K conductances, the latter consisting of a voltage- and a Ca-dependent type. Lizard nodes of Ranvier, like those of the frog, but unlike those of the mouse, exhibit a K conductance. These observations provide an explanation for the differences and similarities in presynaptic wave form configuration between the lizard and the other two species.

The interference of truncated with normal potassium channel subunits leads to abnormal behaviour in transgenic Drosophila melanogaster.

The Shaker locus of Drosophila melanogaster encodes a family of A-type potassium channel subunits. Shaker mutants behave as antimorphs in gene dosage tests. This behaviour is due to the production of truncated A-channel subunits. We propose that they interfere with the function of their normal counterpart by forming multimeric A-channel structures. This hypothesis was tested by constructing transgenic flies carrying a heat-inducible gene encoding a truncated A-type potassium channel subunit together with a normal wild type doses of A-type potassium channel subunits. The altered subunit leads at larval, pupal or adult stages to the transformation of wild type into Shaker flies. The transformed flies exhibited a heat-inducible abnormal leg shaking behaviour and a heat-inducible facilitated neurotransmitter release at larval neuromuscular junctions. By the overexpression of an aberrant A-channel subunit the normal behaviour of transgenic D. melanogaster can be altered in a predictable way.

Placental metastasis from maternal bronchial oat cell carcinoma.

We describe the case of a young pregnant woman with oat cell carcinoma diagnosed by immunohistochemical reactions and ultrastructural study of a mediastinal biopsy specimen. A neonate was delivered by a cesarean section without evidence of carcinoma, but a thorough pathologic examination of the placenta showed intervillous metastasis of the maternal oat cell carcinoma. This case is interesting, since placental metastases from solid tumors are rare (38 reported cases with pathologic examination of the placenta), and 39% of them arise from maternal melanomas.