Clinical characteristics of 80 subjects with KCNQ2-related encephalopathy: Results from a family-driven survey.

Variants of KCNQ2 are associated with a wide spectrum of disorders, ranging from Self-limiting Neonatal Epilepsy (SelNE) to Early Onset Developmental and Epileptic Encephalopathy (KCNQ2-DEE). Comorbidities associated with this end of the spectrum have been seldomly described and their impact on the life of patients and their families is yet to be investigated. Collaborating with caregivers from different European family associations, we have developed a questionnaire aimed at investigating the onset and frequency of epileptic seizures, anti-seizure medications (ASM), hospitalizations, stages of development, and comorbidities. Responses from 80 patients, 40 males, from 14 countries have been collected. Median age 7.6 years (4 months - 43.6 years). Of 76 epileptic patients (93.6%), 55.3% were seizure-free with a mean age at last seizure of 26.7 months. Among patients with active epilepsy, those older have a lower frequency of seizures (p > 0.05). We were able to identify three different clusters of varying severity (Mild, Severe, Profound), based on neurodevelopmental features and symptoms, excluding epilepsy. Patients in a higher severity cluster had a higher mean number of comorbidities, which had a higher impact on families. Notably, patients in different clusters presented different epilepsy onset and courses. This study constitutes the most extensive data collection of patients with KCNQ2-DEE, with a focus on comorbidities in a wide age group. The participation of caregivers helps to define the impact of the disease on the lives of patients and families and can help identify new primary and secondary outcomes beyond seizures in future studies.

Importance of basophils in eosinophilic asthma: the murine counterpart.

Several experimental studies in mice showed that basophils participate in the initiation of Th2 adaptive immune response, in addition to the effector phase. However, the role of basophils in allergic airway inflammation is less clear. The aim of this experiment was to assess the importance of basophils in recruiting inflammatory cells and, in particular, eosinophils in a murine model of asthma induced by Aspergillus fumigatus allergens. Additionally, bronchial reactivity was evaluated. Basophil depletion resulted in a reduction of inflammatory cells in the airways and eosinophil recruitment was significantly impaired. Also bronchial reactivity seemed to be impaired in basophil-depleted mice, but the result was not statistically significant. According to these preliminary data, basophils seem to influence the local eosinophilic response of allergic asthma.

Pentraxin 3 serum levels in children with atopic dermatitis.

PTX3 behaves as an acute-phase response protein as its blood levels rapidly and dramatically increase during endotoxic shock, sepsis, and other inflammatory and infectious conditions. Therefore, this study was designed to investigate a possible role of PTX3 in children with Atopic Dermatitis (AD). One-hundred-and-thirty-six patients (37 females, 99 males, mean age 10.4 years) were enrolled in the study. One hundred patients (74%) had only respiratory symptoms (allergic rhinitis and/or bronchial asthma); thirty-six patients (26%) showed dermatitis associated with respiratory allergy (allergic rhinitis and/or bronchial asthma). PTX3 levels were higher in children with AD and there was a significant correlation between serum PTX3 levels and SCORAD index (p-value=0.0001, rho=0.658). Therefore, this study may show that PTX3 might be a reliable marker for the severity of AD in children with respiratory allergy.

Body mass index is related with bronchial function and reversibility in children with allergic rhinitis and asthma.

Several studies have outlined a possible relationship between an increased body mass index and respiratory allergic diseases, such as asthma and rhinitis.The aim of the study was to analyse the relationship between BMI and lung function, including bronchodilation test, in allergic children. The study included 153 children (103 males, mean age 12.8 years) with allergic rhinitis and mild asthma. All subjects were evaluated performing skin prick test, spirometry, and bronchodilalation test. BMI values were in the normal range as well as lung function. BMI significantly related with FEV1, FVC values and FEV1/FVC ratio both before and after bronchodilation. In conclusion, this study provides the first evidence that BMI is negatively related with bronchial reversibility in children with allergic rhinitis and asthma.As reversibility is related with bronchial inflammation, this finding might underline a link between overweight and allergic inflammation.

A reservoir nasal cannula improves protection given by oxygen during muscular exercise in COPD.

We verified the utility of an oxygen economizer (Pendant Oxymizer) in assuring greater protection than nasal prongs against worsening of oxyhemoglobin resting desaturation (delta SaO2) induced by muscular exercise in 16 patients (ten with chronic obstructive pulmonary disease [COPD] and six with restrictive pulmonary disease). This worsening was quantified as desaturation surface accumulated within five minutes of exercise and was expressed in arbitrary units (au). Each patient carried out the same exercise three times, in a randomized fashion (breathing air or breathing supplemental oxygen [3 L/min] delivered by either nasal prongs or by oxygen economizer). In patients with obstructive disease, delta SaO2 was reduced from 38 +/- 12.0 au when they were breathing air to 18.1 +/- 11.7 au when breathing oxygen by nasal prongs (p less than 0.001) and to 10.1 +/- 9.5 au when breathing oxygen by economizer (p less than 0.001). In patients with restrictive disease, delta SaO2 was reduced from 35.6 +/- 9.9 au when breathing air to 14.9 +/- 10.2 au breathing oxygen by nasal prongs (p less than 0.01) and to 13.7 +/- 10.3 au breathing oxygen by economizer (p less than 0.01). The difference between breathing by economizer and nasal prongs was significant (paired t-test; p less than 0.01) only in patients with COPD. One explanation could lie in the different values of the respiratory rate, which was significantly greater in patients with restrictive disease (20.7 +/- 1.2 breaths per minute at rest and 25.8 +/- 1.5 with exercise) than in patients with obstructive disease (15.3 +/- 1.2 breaths per minute at rest and 20.8 +/- 1.4 with exercise).

Free amino acids in walnut kernels and young seedlings.

We investigated the composition of free amino acids in walnut (Juglans regia L.) seeds (embryo and cotyledons). We also examined xylem transport of free amino acids in young seedlings grown in the absence of external nutrients. A relatively high concentration of free alanine was found in seed tissue, whereas a relatively high concentration of citrulline was detected in young seedlings. Citrulline was the main free amino acid transported in the xylem to stem and leaves. The negligible presence of citrulline, a non-protein amino acid, in the kernel and its presence in high concentrations in all of the tissues of young seedlings, including cotyledons, embryonic axis, taproot and stem, suggest that citrulline is synthesized during walnut germination. We conclude that citrulline plays an important role in nitrogen translocation during walnut germination.

Anaerobic accumulation of amino acids in rice roots: role of the glutamine synthetase/glutamate synthase cycle.

Accumulation of amino acids was studied in rice roots of 3-day-old seedlings subjected for 48h to anaerobic conditions. Alanine and Gaba were the main amino acids accumulated under anoxia. Their synthesis was strongly inhibited by MSX and AZA, inhibitors of glutamine synthetase and glutamate synthase. These activities increased after 8h of anaerobic treatment and, by immunoprecipitation of 35S-labeled proteins, it was shown that glutamine synthetase and ferredoxin-dependent glutamate synthase were synthesized during the treatment. These findings indicate that the glutamine synthetase/glutamate synthase cycle play an important role in anaerobic amino acid accumulation.

Respiratory airflow pattern in patients with chronic airway obstruction.

Previous experimental evidence has shown that in healthy humans inspiratory airflow waveform can be optimized according to minimum rate of work criteria when the respiratory energetic requirements become a substantial fraction of the general metabolism (i.e., during exercise hyperpnea and maximum voluntary ventilation). In patients with chronic airway obstruction (CAO) the relative energetic expenditure devoted to respiration is also greatly enhanced at rest. To investigate the performance of a system also controlling airflow wave pattern in this condition we evaluated by Fourier analysis the harmonic content of respiratory flow waves recorded at rest and during exercise hyperpnea (25 and 50 W on cycloergometer) in 15 patients. The results were compared with those we previously obtained in normal subjects and with some theoretical models. It was found that, while normal subjects display at rest an inspiratory flow waveform reasonably close to a sinusoidal model and adopt a more rectangular and economical flow shape during exercise hyperpnea, patients with CAO show a rather rectangular inspiratory flow shape also at rest, without any remarkable change at higher levels of ventilation. So, in general terms, the airflow pattern employed by patients at rest entails a reduction in the rate of dynamic inspiratory work of about 12% over that required by a sinusoidal waveform, and no further advantage is observed during exercise hyperpnea. Some features of the expiratory flow wave were also analysed. As no model of the respiratory system mechanics presently developed can explain the findings obtained in CAO patients purely on the basis of their altered mechanical parameters, it has been suggested that more complex control of respiratory airflow is operating in this class of patient.

Technical aspects of oxygen saving devices.

Oxygen economizing devices have been extensively studied, both at rest and during muscular exercise, in an attempt to increase the autonomy of a portable oxygen apparatus. The aim of this study is threefold: first, to suggest a simple method to verify in a simple way the technical accuracy of a demand flow oxygen delivery device; second, to suggest how we can monitor in a simple way the clinical efficacy of an economizer; and third, to remember that we can utilize an oxygen saving device to give a better protection than nasal prongs against the worsening of HbO2 desaturation induced by exercise.

A portable oxygen system corrects hypoxemia without significantly increasing metabolic demands.

Some patients with chronic cor pulmonale have hypoxemia only during normal daily activity. This can be corrected by portable oxygen. Whether or not the weight of the apparatus (4.2 kg) adds an additional metabolic demand of sufficient magnitude to cancel or outweigh the advantages of portable oxygen is the subject of this report in 6 patients with chronic obstructive pulmonary disease and 2 with kyphoscoliosis. All received standardized treadmill exercise while breathing room air, and the same exercise with a portable liquid oxygen system sitting on the floor or carried by the patients. The additional load created only a 6.7% increase in CO2 production and did not reverse the supplemental oxygen benefit to arterial oxygen saturation under the experimental conditions of the study.

Value of nocturnal monitoring of transcutaneous O2 and CO2 pressures in adults with respiratory failure.

We have evaluated the reliability of the transcutaneous (t.c.) method of measurement of arterial PO2 and PCO2 in adult man. In 33 simultaneous measurements of 9 normals and 12 patients with a wide range of hypoxemia, we found: t.c. PCO2 = 3.62 + 1.29 PaCO2 +/- 7.3 (r = 0.96) and t.c. PO2 = 11.14 + 0.86 PaO2 +/- 9.89 (r = 0.92). Recalculating t.c. PCO2 to 37 degrees C we can obtain: t.c. PCO2 = 2.7 + 0.97 X PaCO2, stating that there is no significant difference between t.c. PCO2 and PaCO2. The t.c. apparatus detects 10 and 90% O2 pressure changes with a delay of time of about 15 s and 1 min, respectively; the t.c. method is therefore not suitable for detecting changes in PaO2 caused by sleep apnea of short duration. On the contrary the t.c. method provided a useful monitoring of arterial PO2 and PCO2 changes during the night in chronic obstructive pulmonary disease (COPD) and non-COPD patients. A nocturnal monitoring of t.c. PO2 and PCO2 seems: (a) absolutely necessary in non-COPD hypoxemics, especially if total lung capacity (TLC) and/or residual volume (RV) are significantly reduced; (b) not absolutely necessary in COPD hypoxemics, provided they have an enlarged TLC and/or a very expanded RV; (c) advisable in intermediate situations, e.g., in COPD hypoxemics with an associated restrictive disorder caused by heart failure, congestion of pulmonary bed, parenchymal or rib cage disease, in order to establish the optimal concentration of oxygen for each patient and to avoid severe nocturnal hypoxemia without producing a dangerous rise in PaCO2.