Notes: The participation of growth factors (GFs) in the regulation of luteinizing hormone releasing hormone (LHRH) neuronal function has recently been proposed, but little is known about the role played by GFs during early LHRH neurone differentiation. In the present study, we have used combined biochemical and morphological approaches to study the ability of a number of GFs normally expressed during brain development, including basic fibroblast growth factor (bFGF), epidermal growth factor (EGF), insulin and insulin-like growth factor I (IGF-I) to induce survival, differentiation, proliferation, and phenotypic expression of immortalized (GT1-1) LHRH neurones in vitro, at early (3-days in vitro, 3-DIV) and late (8-DIV) stages of neuronal differentiation. Comparison of GF-treated vs untreated neurones grown in serum-deprived (SD) medium demonstrated bFGF to be the most potent, and insulin the least active in promoting neuronal differentiation. Thus, at both 3-DIV and 8-DIV, but especially at 8-DIV, bFGF induced the greatest increase in the total length and number of LHRH processes/cell and in growth cone surface area. bFGF was also the most active at 3-DIV, and IGF-I at 8-DIV, in counteracting SD-induced cell death, whereas EGF was the most potent in increasing [3H]thymidine incorporation. All GFs studied decreased the spontaneous release of LHRH from GT1-1 cells when applied at 3-DIV or 8-DIV, except for insulin which was inactive at both time-points and bFGF which was inactive at 8-DIV. Pre-treatment of GT1-1 cells with a suboptimal (‘priming’) dose of bFGF for 12 h followed by application of the different GFs induced a sharp potentiation of the neurotrophic and proliferative effects of the latter and particularly of those of IGF-I. Moreover, bFGF priming counteracted EGF-induced decrease in LHRH release and significantly stimulated LHRH secretion following IGF-I or insulin application, suggesting that bFGF may sensitize LHRH neurones to differentiating effects of specific GFs during development.

Notes: In this paper, an idealized model of the steady-state phase of the flow in a vertical conduit leading to a sand volcano eruption is developed from first principles. The model assumes that a sand–water mixture flows upwards, driven by an overpressure at the base of a vertical cylindrical conduit (or a two-dimensional fracture) and opposed by gravity, viscous resistance and turbulent drag. The conditions for flow are analysed in detail, and the mechanisms controlling the eruption rates are studied quantitatively. The flow predictions are in accordance with our observations of analogous vigorous sand eruptions at deepwater oil fields. For sufficiently high flow velocities (u 〉 10uT) and small sand fractions (s 〈 0·2), the flow may be well mixed and homogeneous. If these conditions are not met, the flow may either become two phase or does not develop. Combining geological considerations with the steady homogeneous model, it is possible to predict the behaviour of the vigorous quasi-steady stage of a sand volcano eruption. It is shown that, based on the average density of the overlying sediments, there are a range of overpressures for which sand volcanoes may develop.

Notes: Abstract A 15-year-old girl was admitted to ICU in a comatose state. She presented with mydriasis, areflexia, hypoxemia and seizures. She was immediately intubated and connected to a ventilator. The seizures were reversed with intravenous diazepam. CT scan was negative. EEG showed a diffuse fast activity and theta waves with spikes in the anterior and temporal regions, bilaterally. The gastric lavage was suggestive of drug ingestion. The patient completely recovered after 6 h of mechanical ventilation and supportive management. Mydriasis was still present after the resolution of neurological symptoms. The girl told us she had ingested 10 tablets (3 g–55 mg/kg) of Loftyl (buflomedil) for suicidal intention. The buflomedil concentrations at 2–3 h from ingestion were 24.8 mg/l in the blood, 324.4 mg/l in the urine and 6.9 mg/l in the gastric content. The p-desmethyl metabolite was also identified in the urine. Buflomedil is a rheological agent largely used as a vasodilator in some European countries. Some recent reports have emphasized the risk of acute intoxication with this drug. Relatively low doses (50–60 mg/kg) have been associated with an important neurological toxicity and a high mortality. We suggest that the clinical picture we observed might be related to a neuroleptic-type action of buflomedil. We bring to attention the risk of a large, uncontrolled diffusion of a drug capable to cause serious consequences at relatively low doses.

Notes: Abstract Objective The purpose of this study was to investigate whether changes in breathing pattern, neuromuscular drive (P0.1), and the work involved in breathing might help to set the individual appropriate level of pressure support ventilation (PSV) in patients with acute respiratory failure (ARF) requiring ventilatory assistance.Design: A prospective, interventional study. Setting An 8-bed multidisciplinary intensive care unit (ICU). Patients Ten patients with ARF due to adult respiratory distress syndrome (ARDS), sepsis or airway infection were included in the study. Chronic obstructive pulmonary disease (COPD) patients with acute exacerbation were excluded. None of these patients was in the weaning process. Interventions We found a level of pressure support able to generate a condition of near-relaxation in each patient, as evidenced by work of breathing (WOB) values close to 0 J/l. This level was called PS 100 and baseline physiological measurements, namely, breathing pattern, P 0.1 and WOB were obtained. Pressure support was then reduced to 85%, 70% and 50% of the initial value and the same set of measurements was obtained. Measurements and results Flow ( $$\dot V$$ ) was measured by a flow sensor (Varflex) positioned between the Y-piece of the breathing circuit and the endotracheal tube. Tidal volume was obtained by numerical integration of the flow signal. Airway pressure (Paw) was sampled through a catheter attached to the flow sensor. Esophageal pressure (Pes) was measured with a nasogastric tube incorporating an esophageal balloon. The esophageal balloon and flow and pressure sensors were connected to a portable monitor (CP 100 Bicore) that provided realtime display of flow, volume, Paw and Pes tracings and loops of Pes/V, Paw/V and $$\dot V$$ /V relationships. The breathing pattern was analyzed from the flow signal. Patient work of breathing (WOB) was calculated by integration of the area of the Pes/V loop. Respiratory drive (P 0.1) was measured at the esophageal pressure change during the first 100 ms of a breath, by the quasiocclusion technique. When pressure support was reduced, we found that the respiration rate significantly increased from PS 100 to PS85, but varied negligibly with lower pressure support levels. Tidal volume behaved in a similar way, decreasing significantly from PS 100 to PS85, but hardly changing at PS 70 and PS 50. In contrast, WOB and P 0.1 increased progressively with decreasing pressure support levels. The changes in WOB were significant at each stage in the trial, whereas P 0.1 increased significantly from PS 100 at other stages. Linear regression analysis revealed a highly positive, significant correlation between WOB and P 0.1 at decreasing PSV levels (r=0.87), whereas the correlation between WOB and ventilatory frequency was less significant (r=0.53). No other correlation was found. Conclusions During pressure support ventilation, P 0.1 may be a more sensitive parameter than the assessment of breathing pattern in setting the optimal level of pressure support in individual patients. Although P 0.1 was measured with an esophageal balloon in the present study, non-invasive techniques can also be used.

Notes: Abstract Two patients with refractory hypoxemia due to unilateral lung atelectasis were treated with differential lung ventilation (DLV) through a Robertshaw-type, double-lumen tracheostomy tube. DLV was applied using two non-synchronized ventilators and maintained for 6 and 3 days, respectively. Ventilator settings were chosen in accord to the clinical, laboratory and chest X-rays results. Particularly, tidal volume and PEEP were set to avoid excessively high alveolar pressure and to obtain the highest possible value of compliance. We investigated the mechanical properties of the two lungs separately by measuring airway pressure and compliance of each lung before the beginning of DLV and at 0, 5, 24, and 48 h after. Initially we observed in both patients very low values of compliance (7–9 cm H2O/I) and a significant level of PEEPi (12–8 cm H2O) of the diseased lung, whereas PEEPi in the healthy lung was negligible. The clinical improvement was assessed by sequential chest X-rays and by significant improvement of arterial blood gas and PaO2/FiO2 ratios and was associated with a progressive increase of compliance (24–22 cm H2O/I) and by a fall of PEEPi levels (5–4 cm H2O) of the diseased lung. We also observed an improvement of S $$\bar v$$ O2, O2AVI, PVRI and $$\dot Q$$ va/ $$\dot Q$$ t values (Case 1). The tracheostomy tube used to apply DLV was very reliable, allowing easy nursing care and selective bronchial aspirations. We conclude that DLV is a very useful technique in unilateral lung pathology, and it can be a life saving procedure in selected patients, by supplying volume and PEEP more efficiently to the affected lung.