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Background: The treatment of children with juvenile idiopathic arthritis (JIA) to prevent disability is a major challenge in paediatric rheumatology. The presence of synovitis, which is difficult to detect in children, is associated with structural damage. Musculoskeletal ultrasonography (MSUS) can be used in patients with JIA to reveal subclinical synovitis. Objective: The primary aim was to determine whether the use of MSUS was associated with therapeutic modification in patients with JIA. The secondary aim was to identify other factors associated with therapeutic decisions. Methods: We conducted an observational study based on the JIRECHO multi-centre cohort, which was developed to provide a systematic MSUS follow-up for patients with JIA. Follow-up occurred every 6 months and included clinical and MSUS examinations. We included children who underwent MSUS of the elbows, wrists, second metacarpophalangeal joints, knees and ankles, which was performed by expert sonographers. Clinical and biological data, disease activity scores and information on therapeutics were collected. Results: A total of 185 visits concerning 112 patients were recorded. Three groups were defined according to the therapeutic decision: escalation (22%, n= 40), de-escalation (14%, n= 26) or stable (64%, n= 119). In the “therapeutic escalation” group: the presence of ultrasonographic synovitis in B-mode and the presence of grade 2 or 3 synovitis in B-mode were not significantly more frequent than in the “stable therapeutic or de-escalation” group (80% versus 65%, p= 0.06; 33% versus 19%, p= 0.06), and the patient’s and physician’s visual analogue scale (VAS) scores, the clinical JADAS and the C-reactive protein level were significantly higher, but only physician’s VAS score remained in the model of logistic regression. In the “therapeutic de-escalation” group: there was no difference in the presence of US synovitis compared with the “stable therapeutic or escalation” group (62% versus 69%, p= 0.48). Conclusion: Even though US synovitis tended to be more frequent in patients with therapeutic escalation, the study did not show that the presence of synovitis in MSUS was statistically associated with therapeutic modifications in patients with JIA. Treatment remained stable despite the presence of US synovitis.

Las enfermedades autoinflamatorias (EAI) monogénicas son enfermedades raras que comienzan en una etapa precoz de la vida y se caracterizan por la presencia de fiebre recurrente o episódica, asociada a una serie de signos sistémicos inflamatorios y a parámetros de inflamación en las pruebas de laboratorio. Una anamnesis que conste de un árbol genealógico y un análisis semiológico minucioso permiten orientar el diagnóstico, que se confirma a continuación con análisis genéticos. La fiebre mediterránea familiar es la más frecuente y se debe sospechar ante episodios febriles de corta duración (24-72 horas) asociados a dolor abdominal intenso, en un paciente de una etnia de riesgo. El número de EAI monogénicas conocidas ha aumentado significativamente desde que se pueden realizar técnicas de secuenciación de alto rendimiento. Su clasificación basada en su fisiopatología parece ser en la actualidad la más coherente en términos de enfoque terapéutico y de pronóstico. El inicio de una EAI en la edad adulta obliga a sospechar un origen mieloide por un mecanismo de mutaciones somáticas adquiridas debido a un clon mielodisplásico.

Les immunodépressions congénitales et acquises peuvent se compliquer d’atteintes respiratoires touchant les voies aériennes distales. L’objectif de cet article est de faire une mise au point sur les atteintes des voies aériennes distales rencontrées lors des principales causes d’immunodépression.

La peau est l’un des organes les plus fréquemment atteints lors des maladies auto-inflammatoires monogéniques (MAIm). La prévalence des signes cutanés est difficile à estimer, du fait du faible nombre de patients dans les études. L’objectif était de déterminer la prévalence des manifestations cutanées dans les 4 maladies auto-inflammatoires monogéniques historiques : la fièvre méditerranéenne familiale (FMF), le CAPS, le TRAPS et le déficit en mévalonate kinase (MKD).

Background Peripherally inserted central catheters (PICCs) are increasingly used in patients with cystic fibrosis (CF) or with non-CF bronchiectasis, but little data exist on catheter-related complications in this setting.Methods Prospective follow-up of consecutive PICCs inserted for intravenous (IV) antibiotics in adults with CF or with non-CF bronchiectasis at Cochin Hospital (Paris, France).Results Between March 2009 and December 2011, 182 PICCs were prescribed in 117 adults (67 CF and 50 non-CF patients). Ultrasound-guided placement of catheter was successful in 174/182 (95.6%) procedures; no insertion complication occurred. The mean ± SD catheter dwell time was 15 ± 9 days. No catheter-associated bloodstream infection occurred; main complications were symptomatic upper limb deep vein thrombosis (2%), catheter obstruction (18%) and persistent pain after catheter insertion (18%). Patients' satisfaction was high and PICC could be used to perform antibiotic courses in most patients.Conclusions PICCs were generally safe for performing IV antibiotic courses in patients with CF or non-CF bronchiectasis, but prolonged pain and/or catheter obstruction occurred in approximately 20% of cases.

SUMMARY Bevacizumab is an antiangiogenic targeted therapy approved for the treatment of patients with advanced non-small-cell lung cancer other than predominantly squamous cell histology in addition to platinum-based chemotherapy. The safety of bevacizumab has been assessed in studies across most cancer types and bevacizumab is generally well tolerated. Some specific issues associated with the use of bevacizumab in lung cancer are discussed in this report (pulmonary hemorrhage, brain metastases or concurrent thoracic radiotherapy) as well as frequent and clinically relevant adverse events and their management. Oncologists and pulmonologists should be aware of such events and their management since the prescription of bevacizumab concerns many patients and the future use in maintenance therapy will be associated with prolonged treatment.

ABSTRACTAspergillus fumigatusis the most frequent fungus found in the sputum of cystic fibrosis (CF) subjects. Itraconazole is prescribed for allergic bronchopulmonary aspergillosis (ABPA) or Aspergillusbronchitis in CF subjects. We hypothesized that A. fumigatusisolates in the sputum of CF subjects with previous exposure to itraconazole was associated with higher prevalence of azole resistance. From June 2010 to April 2011, sputum samples from adult CF subjects at Cochin University Hospital (France) were examined systematically for the detection of A. fumigatus. MICs of A. fumigatusisolates against azoles were screened using Etest, and reduced susceptibility to azoles was confirmed using the CLSI broth microdilution method. A. fumigatuswas isolated from the sputum of 131/249 (52.6%) adult CF subjects, and 47/131 (35.9%) subjects had received previous treatment with itraconazole. Reduced A. fumigatussusceptibility to itraconazole (MIC, ≥2 mg/liter) was confirmed in 6/131 (4.6%) subjects. All 6 isolates also had reduced susceptibility to posaconazole (MIC, ≥0.5 mg/liter), and 3/6 isolates had reduced susceptibility to voriconazole (MIC, ≥2 mg/liter). Mutations in the cyp51Agene were detected at positions previously implicated to cause resistance in 5 isolates. Azole-resistant A. fumigatusisolates were found in 5/25 (20%) subjects exposed to itraconazole within the previous 3 years. High rates of azole-resistant A. fumigatusisolates were present in adult CF subjects and were associated with recent itraconazole exposure. Although the clinical implications of these findings will require further studies, the cautious use of itraconazole in adult CF subjects can be recommended.

Après Cancun, la relance du processus de négociation dans les réunions de Genève, a permis de surmonter l’échec. La coalition du G20 autour du Brésil, de l’Inde et de la Chine s’est confirmée. L’agriculture est toujours en première ligne, mais les divergences sur les subventions export et interne, sur les formules de réduction des droits de douanes sont toujours très fortes. Les discussions actuelles pourront-elles permettre de passer l’étape d’un accord sur les « modalités » avant le mois de juillet ? Au-delà de cette date, tout serait reporté à 2005 pour causes d’élections américaines.

Gravitactic bioconvective patterns created by Tetrahymena pyriformis in a Hele-Shaw apparatus were realized and compared with theoretical results. There were found to be two thresholds for bioconvection development: the first indicates the transition from the diffusion to the steady convection state; the second corresponds to the transition from the steady to the unsteady convection state. The results showed that the Hele-Shaw apparatus may be used as a physical analogy of porous media to study 2D bioconvection, with possible extensions to larger scale biological systems where population growth and distribution are driven by similar bio-physical interactions. [ABSTRACT FROM AUTHOR]

Background & Aims: With the improved survival of patients with cystic fibrosis (CF), gastrointestinal complications become more evident in adults with this condition. The aims of this study were to determine the prevalence and clinical features of distal intestinal obstruction syndrome (DIOS) and its relationship with the cystic fibrosis transmembrane conductance regulator (CFTR) genotype in an adult CF population. Methods: Cross-sectional study was conducted in an adult CF cohort. Results: Among 171 adults with CF (mean age, 28.9 years), 27 patients (15.8%) reported 43 episodes of DIOS. No significant association was found between DIOS and a history of meconium ileus. The first episode of DIOS occurred in adulthood in 21 cases (77.8%). DIOS recurred in 13 patients (48.1%). All patients who developed DIOS had pancreatic insufficiency. Pulmonary function was significantly more altered in patients with DIOS than in the other patients, but pancreatic insufficiency and age might act as confounding factors. DIOS occurred in 21.9% of patients with a severe CFTR genotype and in only 2.4% of patients with a mild CFTR genotype (P < 0.005). Conclusions: DIOS is frequent in adults with CF with a severe CFTR genotype and/or advanced-stage pulmonary disease. The relative contributions of malabsorption and impaired intestinal secretion in the development of DIOS are discussed.

Accumulating evidence suggests that in cystic fibrosis (CF) patients, airway fluids are characterized by decreased antibacterial activity, elevated NaCl concentration, and high levels of chemokines, resulting in exaggerated activation of the transcriptional nuclear factor (NF)-κB in airway epithelial cells. The present study was undertaken to evaluate the effects of anti-inflammatory cytokine interleukin-10 (IL-10) on NaCl-induced chemokine IL-8 and regulated on activation normal T cell expressed and secreted (RANTES) expression through the NF-κB signaling in primary ΔF508 CF and non-CF (control) human bronchial epithelial cells. Exposure of CF and non-CF bronchial epithelial cells to hypertonic (170 mmol/L NaCl) milieu compared to isotonic (115 mmol/L NaCl) and hypotonic (85 mmol/L NaCl) milieu caused a significant, NaCl-dependent increase in IL-8 and RANTES gene expression and protein production. Compared to non-CF cells, CF bronchial epithelial cells were characterized by a higher susceptibility to produce elevated IL-8 and RANTES production in an hypertonic NaCl milieu in response to IL-1β activation. Treatment with IL-10 suppressed IL-8 and RANTES gene expression in both non-CF and CF bronchial epithelial cells was associated with a reduced expression of IkB (IKK) α/β kinases, particularly for IKKα which is greater expressed in CF bronchial epithelial cells, and resulting in reduced NF-κB activation. These findings suggest that IL-10 might have anti-inflammatory benefits in airways of CF patients.

To assess the follow-up of patients with sarcoidosis and myocardial MRI abnormalities.

Airway inflammation, one of the major factors leading to lung damage in cystic fibrosis (CF) patients, is associated with an abnormal increase in proinflammatory cytokines. In this work, we demonstrate the increased release of the proinflammatory cytokines after lipopolysaccharide (LPS) stimulation: human interleukin (hIL)-8 in CF and non-CF airway xenografts, and hIL-6 and human growth-related oncogene-alpha (hGRO-alpha), which could be only analyzed in non-CF xenografts. Under basal conditions, we observed that hIL-8 was higher in CF xenografts compared with non-CF. We also report the anti-inflammatory effect of a glucocorticoid, fluticasone propionate (FP), on CF airway epithelium using a humanized model of airway inflammation developed in nude mice. In CF and non-CF tracheal xenografts, airway inflammation was induced by inoculating Pseudomonas aeruginosa LPS (4 h; 1 microg/ml) in the lumen of the xenografts. FP pretreatment (2 h; 10(-8) M) followed by P. aeruginosa LPS stimulation induced a significant reduction of LPS-induced hIL-8 release in airway liquid collected from CF and non-CF tracheal xenografts (85 and 80%, respectively). In non-CF tracheal xenografts, FP treatment before LPS stimulation induced a significant decrease in hIL-6 and hGRO-alpha. From these data, we suggest that FP exerts anti-inflammatory properties that may be appropriate to CF therapy, at an early stage of the disease. In addition, these results demonstrate that the humanized airway model of inflammation provides a relevant tool for analyzing the effects of anti-inflammatory drugs in different diseases in which airway inflammation is implicated.

Airway inflammation, one of the major factors leading to lung damage in cystic fibrosis (CF) patients, is associated with an abnormal increase in proinflammatory cytokines. In this work, we demonstrate the increased release of the proinflammatory cytokines after lipopolysaccharide (LPS) stimulation: human interleukin (hIL)-8 in CF and non-CF airway xenografts, and hIL-6 and human growth-related oncogene-α (hGRO-α), which could be only analyzed in non-CF xenografts. Under basal conditions, we observed that hIL-8 was higher in CF xenografts compared with non-CF. We also report the anti-inflammatory effect of a glucocorticoid, fluticasone propionate (FP), on CF airway epithelium using a humanized model of airway inflammation developed in nude mice. In CF and non-CF tracheal xenografts, airway inflammation was induced by inoculating Pseudomonas aeruginosaLPS (4 h; 1 μg/ml) in the lumen of the xenografts. FP pretreatment (2 h; 10−8M) followed by P. aeruginosaLPS stimulation induced a significant reduction of LPS-induced hIL-8 release in airway liquid collected from CF and non-CF tracheal xenografts (85 and 80%, respectively). In non-CF tracheal xenografts, FP treatment before LPS stimulation induced a significant decrease in hIL-6 and hGRO-α. From these data, we suggest that FP exerts anti-inflammatory properties that may be appropriate to CF therapy, at an early stage of the disease. In addition, these results demonstrate that the humanized airway model of inflammation provides a relevant tool for analyzing the effects of anti-inflammatory drugs in different diseases in which airway inflammation is implicated.

In this paper, we deal with linear neutral functional differential systems. Using an extended state space and an extended control operator, we transform the initial neutral system in an infinite dimensional linear system. We give a sufficient condition for admissibility of the control operator B , conditions under which operator B can be acceptable in order to work with controllability and stabilizability. Necessary and sufficient conditions for exact controllability are provided; in terms of a gramian of controllability N(μ) . Assuming admissibility and exact controllability, a feedback control law is defined from the inverse of the operator N(μ) in order to stabilize exponentially the closed loop system. In this case, the semigroup generated by the closed loop system has an arbitrary decay rate.

The inflammatory pathogenesis in airways of patients with cystic fibrosis (CF) is still unresolved. We demonstrate here that in in situhuman ΔF508 homozygous CF bronchial tissues, submucosal gland cells exhibit an absence of inhibitor factor κBα (IκBα) and high levels of chemokine interleukin-8 (IL-8) expression. These results were confirmed by cultured human CF bronchial gland cells in which a lack of cytosolic IκBα and high levels of constitutively activated nuclear factor κB (NFκB) associated with an up-regulation of IL-8 production (13-fold increase) were found when compared to non-CF (control) disease bronchial gland cells. We also demonstrated that the isoflavone genistein, a well known CFTR mutant Cl−channel stimulator, significantly reduces the endogenous and Pseudomonas aeruginosalipopolysaccharide-induced IL-8 production in cultured CF bronchial gland cells by increasing cytosolic IκBα protein levels. Overall, results show that genistein is a potent inhibitor of the activated NFκB identified in CF gland cells. This strong inhibition of constitutively activated NFκB and the resulting down-regulation of IL-8 production by genistein in the CF gland cells highlights the key role played by cytosolic IκBα in the regulation of inflammatory processes in CF human airway cells.

Background: Angiotensin-converting enzyme (ACE) is a peptidase involved in the metabolism of several bioactive peptides. It may be involved in the airway inflammation and hyperresponsiveness that occur in asthma. Objective: We studied the expression of ACE in the airway mucosa of normal and asthmatic subjects and assessed the relationship between ACE expression and airway inflammation and bronchial hyperresponsiveness in asthma. Methods: We used immunohistochemistry to study the ACE expression and airway inflammation in bronchial biopsy samples obtained by fiberoptic bronchoscopy from 20 asthmatic subjects randomly assigned to groups treated with (n = 10) or without inhaled corticosteroids (n = 10) and from normal subjects (n = 10). Airway response to methacholine and bradykinin was also determined for all subjects. Results: In normal subjects ACE was present in the surface epithelium, the endothelial cells of the lamina propria, and the submucosal glands, in which ACE was found in seromucous cells and in secreted mucus. ACE was not detected in smooth muscle cells and in most of the endothelial cells of the vascular network surrounding the glands. ACE was absent or present at lower levels in the surface epithelium of asthmatic subjects not treated with corticosteroids compared with those treated with corticosteroids and the control group. In asthmatic subjects low levels of ACE in the epithelium were associated with larger numbers of eosinophils in the epithelium and lamina propria. There was no relationship between ACE levels in the airway mucosa and airway responsiveness to methacholine and bradykinin. Conclusion: ACE expression is decreased in the epithelium of asthmatic patients and is associated with increased eosinophil inflammation. (J Allergy Clin Immunol 1999;104:402-10.)

Neutral endopeptidase (NEP) (enkephalinase, EC 3.4.24.11) and angiotensin converting enzyme (ACE) are two peptidases that can cleave the C-terminal dipeptide bradykinin(8-9) from bradykinin. To determine whether these peptidases play roles in modulating kinin-induced contractions in the airways, we studied the effects of captopril, an ACE inhibitor, and of leucine-thiorphan and phosphoramidon, two NEP inhibitors, on the contractile responses to bradykinin and lysyl-bradykinin in isolated segments of ferret trachea. Bradykinin and lysyl-bradykinin-induced contractions in a concentration-dependent fashion (P less than .001), with a threshold of 10(-7) M and 5 x 10(-7) M, respectively. In contrast, the bradykinin(8-9) and the N-terminal heptapeptide bradykinin(1-7), the major fragments of hydrolysis of bradykinin by NEP and ACE, had a very weak or no effect on tracheal contraction in concentrations as great as 10(-5) M. Captopril, leucine-thiorphan and phosphoramidon (each inhibitor at 10(-5) M, 15 min) shifted the concentration-response curves to lower concentrations by approximately 1 to 1.5 log U (P less than .05). Both NEP inhibitors and the ACE inhibitor potentiated the response to bradykinin in a concentration-dependent fashion (P = .0001), and the combination of phosphoramidon and captopril resulted in an additive potentiation of bradykinin-induced contraction (P less than .02). [D-Pro2-D-Trp7,9]-substance P, a substance P antagonist, did not modify the potentiation of bradykinin-induced contraction by NEP inhibitors.(ABSTRACT TRUNCATED AT 250 WORDS)

All the described procedures for lecithin: cholesterol acyltransferase (LC AT) determination in the plasma have raised criticisms: Lack of sensitivity for methods using colorimetric determination of unesterified cholesterol or phosphatidyl-choline in plasma before and after incubation at 37 °C. Incomplete isotopic equilibrium of the free cholesterol substrate between the different lipoproteins in radioassay procedures. Gas liquid chromatography methods cannot be used when LCAT activity is low. A new method, easier, more sensitive and accurate has been developed in our laboratory: plasma samples are delipoproteinized by coprecipitation with Intralipid, dextran sulphate, and calcium chloride. Cholesterol esterification is assayed by a short incubation (30 min) of 100 µl delipoproteinized plasma and a 30 µl of 3H-cholesterol-labelled substrate. About 15% of cholesterol is esterified in these conditions in 30 min (35 ± 7 µmole/h/l). The LCAT reaction is linear for about one hour.

A study of 31 observations of congenital toxoplasmosis shows that there is a clear relationship between the cerebral lesions as observed on CT scan, neurological symptoms, and the date of maternal infection. The appearance of the CT scan is characteristic of cases with early maternal seroconversion (before the 20th week of pregnancy), of cases with maternal infection between the 20 and 30th week of pregnancy, and of cases with late maternal seroconversion (after the 30th week of pregnancy). Preventive maternal treatment does not change the pattern of the cerebral lesions observed on CT scan and thus proves ineffective in conferring real protection.

Strictly anaerobic fungus species, present in the digestive tract of herbivores, are widely distributed, as confirmed by the discovery in France ofPiromyces mae Li in sheep rumen. By the study of a new strain, the morphological characteristics of this species were more accurately determined and the presence of megahydrogenosomes in its zoospores confirmed. Chitobiose,N-acetylgalactosamine, and arabinose were demonstrated on the thallic surface with lectins of different affinities for the sporangium or the rhizoids. In contrast toP. communis, there were no surface oligosaccharides with a terminal galactose bound toN-acetylgalactosamine orN-acetylglucosamine by a ß 1?3 bond.

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.

Abstract: The goals of the long-term management of reversible obstructive airways disease (ROAD) are to find the minimum treatment that controls symptoms, allows resumption of normal life, prevents severe attack and death, and controls airflow obstruction. ROADs include asthma, chronic bronchitis, and emphysema. Although the differential diagnosis between these different entities may be difficult, they share the same possibilities of pharmacotherapy, including bronchodilator and antiinflammatory drugs.β 2-agonists administered via inhaled route produce the best bronchodilator/side effects ratio, provided that the drugs reach the bronchi. This underlines the importance of a proper inhalation technique when using a metered-dose inhaler. In patients with hand-breath coordination problems, powder inhalers or spacer devices are useful to ameliorate the therapeutic efficacy of inhaled drugs. Anticholinergic agents are usually less potent bronchodilators than inhaledβ 2 agonists in asthma, but they may have additive effects when associated withβ 2 agonists. Only a therapeutic trial with peak-flow monitoring can demonstrate the efficacy of anticholinergic drugs in individuals. Theophylline’s kinetics are characterized by a narrow therapeutic index with high inter- and intraindividual variabilities. Sodium cromoglycate and nedocromil sodium are antiallergic drugs, the efficacy of which has been demonstrated in controlled studies. Corticosteroids are the most efficient antiasthma drugs. Inhaled corticosteroid dosing should be tailored to each individual. If inhaled corticosteroid therapy is used in an oral corticosparing attempt, patients should be followed-up during several months. The management of ROAD includes the diagnostic procedures, the identification of triggers and inducers of airways obstruction, the assessment of severity of the disease, and then the treatment and education of the patient. Strategy design to achieve proper use of drugs by patients is discussed.

To evaluate the role of airway neutral endopeptidase (NEP) in the regulation of contraction of airway smooth muscle in response to endogenous tachykinins, we studied the effects of the NEP inhibitor phosphoramidon on contractions of guinea pig bronchial smooth muscle strips induced by either electrical field stimulation (EFS) or by capsaicin. In the presence of atropine (10(-6) M), propranolol (10(-6) M), phentolamine (10(-5) M), indomethacin (10(-6) M) and pyrilamine (5 x 10(-6) M) EFS (biphasic; pulse width, 1.0 msec; frequency 0.5-5 Hz for 30 sec; intensity, 20 V) produced noncholinergic, nonadrenergic muscle contraction in a frequency-dependent fashion (P less than .001). Phosphoramidon potentiated the contractile responses to EFS (P less than .01). Leucine-thiorphan (10(-5) M), another NEP inhibitor, potentiated EFS-induced contraction in a similar fashion as phosphoramidon (186 and 182% of control, respectively; each comparison, P less than .025). Captopril, bestatin, leupeptin and physostigmine (each drug, 10(-5) M) were without effect (P greater than .5, N = 5). Capsaicin (1.5 x 10(-8) M) produced long-lasting atropine-resistant smooth muscle contraction, an effect potentiated by phosphoramidon (10(-5) M (P less than .001). Removal of the epithelium slightly but significantly (P less than .05) increased the contractile responses to capsaicin and to EFS at impulse frequencies of 2 and 5 Hz, and phosphoramidon substantially increased contractions in tissues without epithelium. The trachea, bronchi and lungs each contained significant NEP activity.(ABSTRACT TRUNCATED AT 250 WORDS)

All the described procedures for lecithin: cholesterol acyltransferase (LC AT) determination in the plasma have raised criticisms: Lack of sensitivity for methods using colorimetric determination of unesterified cholesterol or phosphatidyl-choline in plasma before and after incubation at 37 °°C. Incomplete isotopic equilibrium of the free cholesterol substrate between the different lipoproteins in radioassay procedures. Gas liquid chromatography methods cannot be used when LCAT activity is low. A new method, easier, more sensitive and accurate has been developed in our laboratory: plasma samples are delipoproteinized by coprecipitation with Intralipid, dextran sulphate, and calcium chloride. Cholesterol esterification is assayed by a short incubation (30 min) of 100 µµl delipoproteinized plasma and a 30 µµl of 3H-cholesterol-labelled substrate. About 15% of cholesterol is esterified in these conditions in 30 min (35 ±± 7 µµmole/h/l). The LCAT reaction is linear for about one hour.

Oxidants have been implicated in the pathogenesis of many inflammatory airway diseases. Neutral endopeptidase (also called enkephalinase, EC 3.4.24.11) is a peptidase that is involved in the degradation of several proinflammatory peptides, such as tachykinins and kinins. Indirect evidence suggests that airway neutral endopeptidase is inactivated by oxidants. To determine whether hydrogen peroxide inactivates neutral endopeptidase, we studied the activity of this peptidase in washed crude preparations of membranes from guinea pig lungs. Washed crude membrane preparations were exposed to increasing concentrations of hydrogen peroxide (1.25-25 mM) in the presence or absence of two different concentrations of catalase (300 and 700 U/mL). Neutral endopeptidase activity was inhibited by hydrogen peroxide in a concentration-dependent fashion (p =.0001). Addition of catalase prevented, in a concentration-dependent fashion, the inhibition of neutral endopeptidase induced by hydrogen peroxide (p =.0001). Mannitol (40 mM) and L-methionine (20 mM) did not prevent inhibition of neutral endopeptidase induced by hydrogen peroxide (2.5 mM). It can be concluded that neutral endopeptidase is inactivated by hydrogen peroxide, an effect that is prevented by catalase. Hydrogen peroxide-induced inactivation of neutral endopeptidase is not mediated by spontaneous generation of either hydroxyl radical or hypochlorous acid in the membrane preparation. Our results suggest that neutral endopeptidase inactivation may occur in airway diseases associated with exposure to or production of oxidants.

Nebulization is a basic treatment for the management of severe acute asthma. Three mechanisms are involved in bronchial obstruction: bronchospasms, inflammation and an increase in bronchial secretions. Combination therapy including β2-sympatheticomimetic and synthetic atropinic drugs is strongly synergistic. In a French multicenter trial including 45 adult patients presenting with asthma, combination of nebulized Berotec® and Atrovent® was studied. It proved to be efficacious in two thirds of the patients. Results were even better for younger patients whose initial peak flow rate was high. Tolerance to this combination therapy was as good as that to β2-sympatheticomimetic monotherapy.

Of 44 infants and children (neonates excluded) with ischemic strokes of arterial origin documented by CT scan and/or cerebral angiography, idiopathic strokes, occurring in 22 cases, accounted for half the total. Eight of these patients had basal ganglia and/or capsular infarcts without cortical involvement. The outcome in the idiopathic group was favorable: after an average follow-up duration of 48 months, no child had recurrence, two children developed secondary epilepsy, and only two were severely mentally retarded. However, residual dystonia and dyskinesia constituted an incapacitating handicap, having been observed in 14 children of the idiopathic group and in 18 of the whole series. It may be concluded from the present study that the long-term prognosis of ischemic strokes in children is excellent except for the risk of secondary evolutive dystonia in the absence of any detectable cause. (JChild Neurol1986;1:131-136)

Abstract: To determine the responsibility of alveolar macrophage (AM) for the increased concentration of angiotensin-converting enzyme (ACE) in bronchoalveolar fluid of patients with sarcoidosis, we cultured AM recovered by bronchoalveolar lavage of 30 subjects: 9 were normal control subjects (group C), 10 had intrathoracic localized sarcoidosis (group LS), and 11 had disseminated intrathoracic and extrathoracic sarcoidosis (group DS). Cells were cultured for 7 days and synthesis of ACE was evaluated according to the difference between final (ACEqe) and initial (ACEqi) ACE content. In groups C, LS, and DS, ACEqi were, respectively, 3.0 � 1.7, 3.3 � 1.9, and 4.8 � 2.4 U/106 AM, and ACEqe were 6.2 � 1.7, 6.7 � 2.5, and 11.3 � 2.8 U/106 AM. ACEqe was higher than ACEqi in all 3 groups (p < 0.01). When cycloheximide was added to the AM culture, ACEqe did not differ from ACEqi, in opposition to what was observed without cycloheximide (p < 0.002). ACEqi in group LS and DS did not differ from ACEqi in Group C, but ACEqe in Group DS was higher than in Groups C and LS (p < 0.01). We conclude that AM both from normal subjects and from subjects with sarcoidosis contain ACE, cultured AM synthesize ACE, and that a greater amount of ACE is produced when AM are obtained from patients with disseminated sarcoidosis.

While studying the correlation between brain potentials and other variables, such as heart rate, blood pressure, and metabolic rate, Lindsley and Rubenstein1found that in four cases the alpha frequency varied greatly during the midmenstrual period. They did not report, however, that there is a relation between brain potentials and the menstrual cycle. The present study was undertaken because such a relation seemed possible. This possibility was strengthened by the observation of Irving, Reid and Gibbs2that the electrical activity of the cerebral cortex is slowed during pregnancy.

Zusammenfassung 1.In den in dieser Arbeit mitgeteilten Versuchen wird mit einer neuen Methode, der derschichtweisen Thermokoagulation der Großhirnrinde, die Erage nach dem Ursprung der motorischen Reaktionen auf elektrische Rindenreizung experimentell entamiert.2.Das Hauptergebniss dieser Versuche ist, daß fast unmittelbar nach der selektiven Abtötung der Nervenzellen der drei oberflächlichen Schichten der präzentralen Rinde (Areae 4 und 6Brodmanns) genau dieselben Rindenreaktionen mit genau demselben Schwellenwert bei monopolarer Reizung hervorgerufen werden können wie an der normalen Rinde.3.Zum Zustandekommen dieser motorischen Rindenreaktionen genügt somit das alleinige (lebend) Vorhandensein der zwei innersten Rindenschichten und deren elektrische Reizung.4.Die ausgeführte histologische Kontrolle macht es äußerst wahrscheinlich, daß diese Reaktionen, hervorgerufen durch elektrische Reizung einer motorischen Rinde, an der die Nervenzellen der drei oberflächlichen Schichten abgetötet (und verschwunden) sind, auf die direkte Reizung der großen Pyramidenzellen und (oder) der Riesenpyramidenzellen der 4. Schicht dieser Rinde zurückzuführen sind.5.Das sub 2. angeführte Ergebnis und die daraus unabweislich folgende Schlußfolgerung, sub 3. angeführt, gestatten nicht eine Aussage über die Frage, ob bei elektrischer Reizung der normalen Rinde die dann vorhandenen drei oberflächlichen Schichten am Zustandekommen der motorischen Reaktionen teilhaben. Dieses Problem wird in einer späteren Arbeit eruiert werden.

Local strychninization of those structures of the central nervous system which subserve sensory functions results in marked, typical symptoms of sensory excitation. This has been established in previous experiments for the dorsal gray horns or pillars of the spinal cord and for the sensory cortex. In 1929 and 1930 we applied this method in a study of the sensory functions of the optic thalamus of the cat1 by injecting a minute quantity of a solution of strychnine into that part of the central nervous system. The present paper deals with a similar investigation of the optic thalamus of the monkey (Macacus rhesus). Here, again, it was found that local strychninization of various parts of the thalamus results in a typical syndrome and that a definite functional localization in this chief subcortical sensory center exists. METHODS The animals were all Macacus rhesus. Fifty-eight monkeys were used, each of which received

Recently the method of laminar thermocoagulation has been described1 as a method of approach to the physiology of the various layers of the cerebral cortex.It was established that local application of moderate heat for short periods to the exposed surface of the cortex results in destruction of its nerve elements. "Dosing" the heat applied allows the limitation at will of the depth of the lesion to any number of consecutive cortical layers. Thus, application of 65 C. for two seconds destroys the two superficial layers, 70 C. for three seconds, the three outer layers, and 70 C. for four seconds, the four outer layers; application of 80 C. for five seconds destroys all the layers.For a description of the technic and of the necessary simple equipment we refer the reader to the papers already published.1 In this communication we shall discuss the pathologic observations, especially some

Since the discoveries of Hitzig (1870), knowledge of the functions of the cerebral cortex has been vastly increased. The methods of extirpation of various parts and areas of the cortex and of electrical and chemical stimulation have yielded and still yield valuable information. Notwithstanding this remarkable progress, insight is still lacking into many fundamental problems. One of the principal reasons for this obscurity is undoubtedly the stupendous complexity of the structure of the cortex, concerning which even modern histologic methods warrant only a vague surmise. I refer here especially to the complexity of the cortex in cross-section, in a direction perpendicular to the surface.One finds here, more or less distinctly in various regions of the cortex, an arrangement of the myriads of nerve cell bodies in a few layers. A fundamental subdivision in six layers is nowadays generally accepted. This arrangement is suggestive of separation and difference in function;