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Aim of the study We analyzed the temporal trends in characteristics, therapy and outcomes over two decades of younger chronic heart failure (CHF) patients enrolled in our nationwide registry. Methods Among the 14823 CHF patients enrolled in the registry since January 1999 through May 2018, 5465 (37%) were aged Results From 1999 to 2018 the proportion of patients As shown in the Table, the proportion of women, diabetes, ischemic etiology and renin-angiotensin system inhibitor prescription did not change significantly among the three enrollment epochs, whereas preserved LVEF phenotype and prevalence of its driving risk factors increased. The proportion of guideline-recommended drug & device therapies significantly rose over time. All-cause mortality at 1-year follow-up decreased significantly across the 3 epochs studied (Figure). Conclusions During 20 years, the clinical characteristics, the implementation of recommended treatments and prognosis of patients Figure 1 Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): Fondazione per il Tuo cuore – HCF onlus

Dystonia is a disorder of both motor and sensory function, clinically characterized by involuntary movements, abnormal postures, and abnormal sensory discrimination. Whereas most data on the physiology of motor cortices are consistent with a general frame of reduced inhibition and maladaptative plasticity, electrophysiological data in sensory cortices are controversial. Habituation refers to response decrement with repeated stimulation, and reflects mechanisms that alter synaptic effectiveness in the stimulated cortex through LTD or LTP-like phenomena. We investigated somatosensory evoked potentials (SEPs) habituation in patients with dystonia and hemifacial spasm (HSF). We recorded median-nerve SEPs in 28 patients (8 cranial, 4 cervical, 1 cranial-cervical dystonia, 15 HSF) and 18 age-matched controls. We measured N20-P25 amplitudes from 3 blocks of 200 sweeps, and assessed amplitude of block 1, and habituation from amplitude changes between the 3 sequential blocks. ANOVA showed a main effect of factor group ( F =4.4 p =0.015). In patients with dystonia, SEP amplitudes were normal in block 1, but thereafter failed to habituate ( p =0.03). Patients with hemifacial spasm had normal SEP amplitudes and habituation ( p =0.98). SEP habituation is altered in dystonia indicating that somatosensory cortex becomes hyperresponsive. This abnormality is not the result of involuntary movements because in patients with HSF SEPs habituate normally.

Negative-pressure ventilation (NPV) was the primary mode of assisted ventilation for patients with acute respiratory failure until the Copenhagen polio epidemic in the 1950s, when, because there was insufficient equipment, it was necessary to ventilate patients continually by hand via an endotracheal tube. Thereafter, positive-pressure ventilation was used routinely. Since it was also observed that patients with obstructive sleep apnoea could be treated noninvasively with positive pressure via a nasal mask, noninvasive positive-pressure ventilation (NPPV) has become the most widely used noninvasive mode of ventilation. However, NPV still has a role in the treatment of certain patients. In particular, it has been used to good effect in patients with severe respiratory acidosis or an impaired level of consciousness, patients that to date have been excluded from all prospective controlled trials of NPPV. NPV may be used in those who cannot tolerate a facial mask because of facial deformity, claustrophobia or excessive airway secretion. NPV has also been used successfully in small children, and beneficial effects on the cardiopulmonary circulation maybe a particular advantage in children undergoing complex cardiac reconstructive surgery. This review is divided into two parts: the first is concerned with the use of negative-pressure ventilation in the short term, and the second with its use in the long term.

To define the extent of damage caused by an ischemic lesion of the left midlateral upper medulla in a 75 year-old patient we performed extensive neurophysiological assessment including somatosensory- and laser-evoked potentials from the upper limbs, exteroceptive and nociceptive blink reflex (tested using a concentric planar electrode), masseter inhibitory reflex and trigeminal laser-evoked potentials. Cutaneous laser stimulation of the right hand failed to evoke any cortical response; somatosensory evoked potentials, exteroceptive and nociceptive blink reflex, masseter inhibitory reflex, and trigeminal laser-evoked potentials were normal on both sides. Neurophysiological data proved the involvement of the left spinothalamic tract and the sparing of the trigeminal descending nucleus, ventral secondary ascending trigeminal pathways, and dorsal column-medial lemniscus sensory pathway. Neurophysiological findings, along with clinical and instrumental evidence of ipsilateral palatolaryngeal palsy indicating damage of the nucleus ambiguous, allow the diagnosis of Avellis’ syndrome, a rare brainstem syndrome originally described in 1891. Routine use of neurophysiological techniques provides precise identification of the neural structures involved in small medullary syndromes, thus refining diagnosis and favouring a precise identification of the vascular territory involved.

Habituation is defined as “a response decrement with repeated stimulation”. In normal cerebral cortex repetitive stimulation delivered with various sensory modalities elicits responses characterized by habituation, presumably owing to mechanisms that alter synaptic effectiveness. Habituation may represent an early, pre-clinical marker of synaptic dysfunction. In dementia, evidence of changes in synaptic functioning in sensory cortices is lacking. We investigated somatosensory evoked potentials (SEPs) habituation in 29 patients with mild dementia, grouped according to clinical, neuropsychological, and neuroimaging features. We recorded median-nerve SEPs in 15 AD-type and 14 VD-type, mild dementia, and 15 controls. We measured N20-P25 amplitudes from 3 blocks of 200 sweeps, and assessed amplitude of block 1, and habituation from amplitude changes between the 3 sequential blocks. ANOVA showed a main effect of factor group ( F = 3.43 p = 0.042). AD-type patients, had normal block1 SEP amplitudes, but abnormal habituation ( p = 0.036). VD-type patients had normal SEP amplitudes and habituation ( p = 0.58). SEP habituation is altered in AD-type dementia suggesting hyperresponsivity of the somatosensory cortex. This abnormality is not found in patients with VD-type mild dementia, which manifest normal synaptic function to repetitive stimulation. Further investigation is deserved to see whether abnormal SEP habituation may represent a neurophysiological marker of degenerative dementia.

The force-generating ability of the parasternal intercostals is maintained during acute hyperinflation in the dog (Jiang et al. Am. Rev. Respir. Dis. 139: 522–528, 1989). In the present studies, we assessed whether the ability of these muscles to expand the rib cage and inflate the lungs is really maintained. We thus measured the electromyogram and the changes in length of these muscles, the axial motion of the sternum and the ribs, and the changes in pleural pressure and tidal volume in anesthetized vagotomized phrenicotomized dogs during selective parasternal stimulation and during spontaneous breathing at different lung volumes corresponding to 0, 5, 10, and 15 cmH2O positive airway pressure. Compared with functional residual capacity, parasternal stimulation at 15 cmH2O positive airway pressure caused a mild decrease in muscle shortening, a large reduction in cranial rib motion, and a large reduction in pleural pressure fall. The caudal displacement of the sternum, however, was increased. Similar alterations in rib and sternal motions and in muscle shortening were seen during spontaneous breathing; tidal volume was markedly reduced as well. These observations thus indicate that hyperinflation affects the action of the parasternal intercostals on the rib cage; their rib-elevating action is decreased, whereas their action on the sternum is increased. As a result, their ability to inflate the lung is reduced. Thus, the inflationary actions of both the diaphragm and parasternal intercostals are reduced by hyperinflation.

Although all the well-recognized muscles of expiration are paralyzed after traumatic transection of the lower cervical cord, tetraplegic subjects can still empty their lungs actively by contracting the clavicular portion of the pectoralis major. It is not known, however, whether contraction of this muscle bundle may raise pleural pressure enough to cause dynamic compression of the intrathoracic airways, which is critical for the production of an effective cough. To investigate this question, we measured expiratory flow rate and esophageal pressure during a series of forced expiratory vital capacity (VC) maneuvers in twelve subjects with C5-8 traumatic tetraplegia and constructed isovolume-pressure flow (IVPF) curves. The curves were interpretable with certainty in nine patients. Three of them did not show any plateau of flow. On the other hand, six patients had clearcut plateaus of flow on all IVPF curves between 80-60 and 20% VC, suggesting they had dynamic airway compression. Videoendoscopic recordings in two patients confirmed trachea and main bronchi collapse during forced expiration and cough. We conclude, therefore, that contraction of the pectoralis major causes dynamic airway compression during expiratory efforts in a substantial proportion of tetraplegic subjects. Increasing the pressure-generating capacity of this muscle might thus improve the effectiveness of cough and reduce the prevalence of bronchopulmonary infections.

Background: We investigated whether chronic headache related to medication overuse (MOH) is associated with changes in brain mechanisms regulating inhibitory cortical responses compared with healthy volunteers and episodic migraineurs recorded between attacks, and whether these changes differ according to the drug overused. Subjects and Methods: We studied 40 MOH patients whose symptoms were related to triptans alone, non-steroidal anti-inflammatory drugs (NSAIDs) or both medications combined, 12 migraineurs and 13 healthy volunteers. We used high-intensity transcranial magnetic stimulation over the primary motor cortex to assess the silent period from contracted perioral muscles. Results: In MOH patients the cortical silent period differed according to the type of headache medication overused: in patients overusing triptans alone it was shorter than in healthy volunteers (44.7 ± 14.2 vs. 108.1 ± 30.1 ms), but similar to that reported in migraineurs (59.9 ± 30.4 ms), whereas in patients overusing NSAIDs alone or triptans and NSAIDs combined duration of silent period was within normal limits (80.6 ± 46.4 and 103.8 ± 47.2 ms). Conclusions: Compared with episodic migraineurs, MOH patients overusing triptans have no significant change in cortical inhibition, whereas those overusing NSAIDs have an increase in cortical inhibitory mechanisms. We attribute these changes to medication-induced neural adaptation promoted by changes in central serotonin neurotransmission.

To assess the respiratory response to abdominal and rib cage muscle paralysis, we measured tidal volume, esophageal and gastric pressures, arterial blood gases, and the electromyogram (EMG) of the diaphragm during progressive epidural anesthesia (lidocaine 2%) in 35 supine anesthetized dogs. The EMG activity of the diaphragm was measured with fine-wire electrodes; the abdominal cavity was thus left intact. Paralysis of the abdominal muscles alone did not produce any alterations. In contrast, when all rib cage muscles were also paralyzed, there were substantial increases in the peak height and the rate of rise of diaphragmatic EMG activity that were associated with a decrease in tidal volume and an increase in arterial PCO2 (PaCO2); swings in transdiaphragmatic pressure, however, were unchanged. The increased diaphragmatic activation due to rib cage muscle paralysis persisted after bilateral cervical vagotomy and was well explained by the increased PaCO2. These observations indicate that in the dog 1) the rib cage muscles contribute significantly to tidal volume, and their paralysis causes, through the increased hypercapnic drive, a compensatory increase in diaphragmatic activation; and 2) the rib cage inspiratory muscles enhance the diaphragm's ability to generate pressure during breathing.

Background Medication-overuse headache (MOH) is a frequent, disabling disorder. Despite a controversial pathophysiology convincing evidence attributes a pivotal role to central sensitization. Most patients with MOH initially have episodic migraine without aura (MOA) characterized interictally by an absent amplitude decrease in cortical evoked potentials to repetitive stimuli (habituation deficit), despite a normal initial amplitude (lack of sensitization). Whether central sensitization alters this electrophysiological profile is unknown. We therefore sought differences in somatosensory evoked potential (SEP) sensitization and habituation in patients with MOH and episodic MOA. Methods We recorded median-nerve SEPs (3 blocks of 100 sweeps) in 29 patients with MOH, 64 with MOA and 42 controls. Episodic migraineurs were studied during and between attacks. We measured N20-P25 amplitudes from 3 blocks of 100 sweeps, and assessed sensitization from block 1 amplitude, and habituation from amplitude changes between the 3 sequential blocks. Results In episodic migraineurs, interictal SEP amplitudes were normal in block 1, but thereafter failed to habituate. Ictal SEP amplitudes increased in block 1, then habituated normally. Patients with MOH had larger-amplitude block 1 SEPs than controls, and also lacked SEP habituation. SEP amplitudes were smaller in triptan overusers than in patients overusing nonsteroidal anti-inflammatory drugs (NSAIDs) or both medications combined, lowest in patients with the longest migraine history, and highest in those with the longest-lasting headache chronification. Conclusions In patients with MOH, especially those overusing NSAIDs, the somatosensory cortex becomes increasingly sensitized. Sensory sensitization might add to the behavioral sensitization that favors compulsive drug intake, and may reflect drug-induced changes in central serotoninergic transmission.

Subjects with traumatic tetraplegia use the pectoralis major to compress the upper rib cage and increase intrathoracic pressure during cough. It is not known, however, whether they also contact the diaphragm during the expiratory phase of cough, as normal subjects do. We have investigated the action of the diaphragm during single voluntary coughing efforts in subjects with complete transection of the lower cervical (n = 5) or midthoracic (n = 2) cord. All subjects showed at least one peak of transdiaphragmatic pressure during the expiratory phase of the effort, and simultaneous bursts of electrical activity were recorded from the diaphragm. Coughing also resulted in an outward (paradoxical) motion of the abdomen during the compressive phase. We conclude that antagonistic contraction of the diaphragm is present during the expiratory phase of cough in spinal cord-injured subjects with paralysis of the abdominal muscles; this contraction, therefore, does not occur in response to activation of these muscles. The present results also indicate that the cough-induced paradoxical expansion of the abdomen is due to contraction of the pectoralis major and not of the diaphragm.

To examine how anesthetized dogs compensate for the diaphragmatic shortening that occurs during head-up tilting, we measured the electroneurogram (ENG) of the C5 phrenic root and the electromyographic (EMG) activity of the parasternal intercostal and transversus abdominis muscles in eight spontaneously breathing animals during postural changes between supine (0 degree) and 80 degrees head-up. Both steady state ENG and EMG activities and first breath responses to tilting from 80 degrees head-up to supine were studied. These experiments have shown that: (1) anesthetized dogs respond to head-up tilting by increasing the neural drive to the costal diaphragm and parasternal intercostals; (2) this response, however, does not occur on the first breath and therefore cannot compensate for the immediate changes in diaphragmatic length; (3) the abdominal muscles, in contrast, show a first breath response to tilting and their activation is primarily responsible for the maintenance of tidal volume. Unlike in humans, increases in neural inspiratory drive in head-up anesthetized dogs are mediated by a chemoreceptive, rather than proprioceptive, feedback mechanism.

New diagnostic and therapeutic aspects of the essential thrombocythemia are summarized. A series of 14 patients with essential thrombocythemia is reported.

Background and aim Dyslipidemia is one of the main risk factors for atherosclerosis, usually the underlying cause of cardiovascular diseases which are the major cause of morbidity and mortality in developed countries. The aim of this study was to assess the effects and the advantages of a combined dietary supplementation with PUFA n-3, vitamin E, niacin and γ-oryzanol on lipid profile, inflammatory status and oxidative balance. Methods and results Fifty-seven dyslipidemic volunteers were randomly assigned to receive: placebo (group A, 19 subjects); PUFA n-3 and vitamin E (group B, 18 subjects); the same as B plus γ-oryzanol and niacin (group C, 20 subjects). Lipid profile, reactive oxygen species (ROS), total antioxidant capacity (TAC), vitamin E, interleukin 1-β (IL1-β), tumor necrosis factor (TNF-α) and thromboxane B 2 (TXB 2 ) were determined at baseline (T0) and after four months (T1). All dyslipidemic subjects showed, at baseline, oxidative stress and, after four months, all biochemical markers improved significantly in groups treated with dietary supplementation. Particularly in group C all lipid patterns improved significantly. Conclusions Our findings demonstrate that the strategy of combining different compounds, which protect each other and act together at different levels of the lipid chain production, improves lipid profile, inflammatory and oxidative status, allowing us to reduce the dose of each compound under the threshold of its side effects.

To date we lack official data on tipology of Diagnosis Related Groups (DRGs) and their quality in Italian Respiratory Intermediate Care Units (RICUs).The objective of the study was to collect data on the activity of 26 Italian RICUs and to evaluate the quality of the DRGs generated.The primary and secondary diseases, the procedures carried out and their coding using the ICD9 system (valid Italy until 2000) were collected from the discharge forms of patients admitted to RICUs. To obtain the DRG, these codes were automatically recoded in the ICD9-CM classification system by Grouper 10. Afterwards, the same diseases and procedures were directly processed by the ICD9-CM classification system. Finally, in order to evaluate the quality of care, the DRGs generated by the ICD9 classification system were compared to DRGs generated by the ICD9-CM classification system.The average weight of the patients cared for in an Italian RICU was 2.05 using the ICD9 classification system and 2.53 using the ICD9-CM classification system. Some non-complicated DRGs (80-97) or non specific DRGs (101-102) were set to zero; others, like DRG 87 appear due to the ability of the ICD9-CM classification system to recognise and accept the fifth digit of the Respiratory Failure code (518.81). The difference in terms of DRG scores generated by the two codification systems was 360.5 DRG points in favour of ICD9-CM. More than 1 million Euro of reimbursements have been lost, as the average national reimbursement for each DRG score is Euro 2,943.80.Severe pulmonary diseases determined the case mix of patients cared for in the Italian RICUs during the observed period. The Italian RICUs offer high quality assistance and are characterised by high mean weight per treated patient. However, the activity has been under-estimated due to the low sensitivity of the ICD9 classification system used in the recognition of the real disease and in the correct generation of relative DRG. The ICD9 classification system penalised the recognition of respiratory failure in particular.

40 subjects who had a transitory ischemic cerebral attack were treated with Mesoglycan and controlled for two consecutive years. Only four patients showed relapse of ischemic cerebral attacks. There was also noted a positive effect on the patients' quality of life, examined using psycometric scales.

A dysfunction of dopaminergic systems with reduction of active dopamine, is well-known in cerebral involution. Twenty patients with mild-moderate pathological cerebral involution of atrophic and/or vascular origin, were treated with Selegiline (L-deprenyl), a monoamino-oxidase B inhibitor (10 mg/die for six months). Compared with a control group, Selegiline treated patients showed a statistically significant improvement in cognitive and behaviour capacities. At the end of investigation, "Mini Mental State" showed an improvement of 26.5% in Selegiline group and of 3.7% in control group (P0.01). "Echelle Clinique d'Aptitudes Intellectuelles" showed an improvement of 29.4% and of 10.8% respectively (P0.01). Selegiline treatment has shortened significantly the reaction times and has improved mnesic capacities. No side effects were observed during the study.

30 patients, affected by chronic ethylic hepatopathy, were treated with 450 mg/daily of ursodeoxycholic acid (UDCA): after six months, a significant decrease of serum hepatic enzymes was noted. The addition of silymarin (400 mg/daily) to UDCA in other 30 patients, induced a further improvement of hepatic function.

The effects of Citicoline were investigated in 40 patients with pathological cerebral involution of atrophic origin. The dose was 1000 mg/die by parenteral injection for 4 weeks; 20 patients, after a wash-out of a week, received another cycle of Citicoline at the same doses for other 4 weeks. Citicoline treatment has shortened significantly the reaction times and has improved cognitive and behaviour capacities, evaluated according to the "Clifton test" and "Green Relatives Stress Scale". Better results were obtained in patients who received two cycles of therapy. No side effects were observed during the study.

We describe a patient with a microangiopathic hemolytic anemia, associated with thrombocytopenia, in consequence of breast cancer in an advanced phase. Microangiopathic hemolytic anemia is a rare and serious compliance of malignant neoplasms, in particular of breast and gastric carcinomas. Microangiopathic hemolytic anemia has always a serious prognosis: survivance in non-treated patients is of a few weeks. Our patient, treated by chemotherapy, has gained a partial remission of MHA, with a reduction of blood transfusions.

Static mouth pressure during maximal inspiratory efforts is commonly used to evaluate inspiratory muscle strength. However, maximal inspiratory pressure (MIP) presents some potential limitations likely to be overcome by the measure of mouth pressure during a maximal sniff maneuver in patients with respiratory muscle weakness. The aim of the present study was to assess whether mouth pressure during sniff maneuver (Pmosn) is a better index of inspiratory muscle strength than MIP in patients with neurologic and neuromuscular diseases (NNMD) with and without inspiratory muscle weakness.Both MIP and Pmosn were measured in 30 patients affected by various types of NNMD and in 41 control subjects. Pmosn was measured with a 5-cm latex balloon-catheter system, the balloon being held in the oral cavity with the lips closed.In control subjects, MIP was either similar (in female subjects) or higher (in male subjects) than Pmosn, the variation coefficients for the two tests being similar both in male subjects (19.3% vs 19.1% for MIP and Pmosn, respectively) and in female subjects (27.5% vs 26.2%, respectively). There was no difference in the Pmosn/MIP ratios observed in the different diseases (one-way analysis of variance, F = 0.29, p = 0.91). In control subjects, a significant inverse relationship between Pmosn/MIP ratio and MIP (r = - 0.66, p0.00001) was found, ie, the lower the MIP, the higher the Pmosn/MIP ratio, suggesting an increasing difficulty in performing MIP as MIP values decreased. The majority of patients were between the prediction limits of the regression calculated for control subjects. At variance, patients with Duchenne dystrophy and low MIP were under the prediction limits of the regression calculated for control subjects, indicating a lower-than-expected PMOSN.In patients with NNMD, irrespective of the etiology, we found the following: (1) Pmosn does not overcome the limitations of MIP measurement; (2) the two maneuvers are not interchangeable, but rather complement one another in the assessment of inspiratory muscle strength; (3) Pmosn may underestimate muscle strength as assessed by MIP in patients with NNMD with inspiratory muscle weakness; and (4) in patients with low MIP, the lower-than-expected Pmosn/MIP ratio confirms inspiratory muscle weakness.

Chronic expiratory flow limitation and hyperinflation are the mechanical hallmarks of chronic obstructive pulmonary disease (COPD). Although carbon dioxide retention is dependent on the severity of airflow limitation, there is considerable variability in the relationships between arterial carbon dioxide tension (Pa,CO2) and forced expiratory volume in one second (FEV1) or total lung resistance (RL). In stable COPD patients with severe airflow obstruction, shallow breathing and inspiratory muscle weakness are the main factors associated with CO2 retention. In stable COPD patients, the diaphragm is less effective than in normal subjects and, with increasing airflow obstruction and hyperinflation, the contribution to the generation of ventilatory pressure of the ribcage inspiratory muscles increased. Abdominal muscles are recruited during expiration in severe COPD patients and the expiratory rise in gastric pressure is directly related to intrinsic positive end-expiratory (alveolar) pressure (PEEPi). During acute bronchoconstriction, COPD patients with severe airflow obstruction recruited the rib cage inspiratory muscles proportionally more than the diaphragm. The associated recruitment of abdominal muscles results in a reduction in abdominal volume at end-expiration and contributes to a significant extent to PEEPi. Dynamic hyperinflation can be overestimated during chronic and acute airway obstruction if abdominal muscle function is not evaluated.

Pulmonary hyalinizing granuloma is an uncommon disease that consists of slowly enlarging nodules in the pulmonary parenchyma. It occurs rarely: in fact, fewer than 70 case reports have been published in the past 20 years. It is important however in the differential diagnosis of lung diseases manifesting multiple pulmonary nodules. The etiology and pathogenesis of this disorder are unknown. Evidence suggests that the nodules could be the result of a chronic exaggerated immune response to infectious agents or to any other process in which antigen-antibody complexes are involved. More than 50% of the patients reported have evidence of autoimmune phenomena, e.g. positive antinuclear antibodies, a positive rheumatoid factor, or circulating immune complexes. The present report describes, for the first time, a case of pulmonary hyalinizing granuloma in which the patient had antineutrophil cytoplasmic autoantibodies with a granular cytoplasmatic pattern with typical central accentuation of fluorescence intensity and negative nuclei. The presence of antineutrophil cytoplasmic autoantibodies suggests that pulmonary hyalinizing granuloma could be regarded as a localized, non-evolving, form of Wegener's granulomatosis or a purely granulomatous Wegener's granulomatosis.

Negative pressure ventilators act by exposing the surface of the chest wall to subatmospheric pressure during inspiration. During negative pressure ventilation (NPV), tidal volume is related to the peak of the inspiratory negative pressure and the pressure waveform generated by the ventilator pump; for the same peak of negative pressure a square wave produces a greater tidal volume than a half sine wave. Several uncontrolled studies suggest that NPV may have a potential therapeutic role in the treatment of acute on chronic respiratory failure in patients with chronic obstructive pulmonary disease (COPD), reducing the need for endotracheal intubation. Recently, NPV has been used with a good outcome as a first-line treatment in COPD patients with severe acute respiratory failure and hypoxic hypercapnic coma. The positive results of these reports need to be confirmed by further controlled studies before recommending the generalized use of NPV in COPD patients with acute respiratory failure as standard care.

Whether or not short-term negative pressure ventilation (NPV) improves respiratory function by decreasing the drive to the respiratory muscles in hypercapnic chronic obstructive pulmonary disease (COPD) patients remains to be defined. In six severely obstructed hypercapnic COPD patients (Group A) with grade IV dyspnoea (modified Medical Research Council (MRC) dyspnoea scale), we evaluated pulmonary volumes, arterial blood gases, the pattern of breathing (tidal volume (VT) and respiratory frequency (Rf)) and the neuromuscular respiratory drive (NMRD), before and immediately after a 7 day period with the iron lung (IL). NMRD was assessed by expressing mouth occlusion pressure (P0.1) recorded during quiet breathing as a percentage of maximal P0.1 recorded during exogenous CO2 stimulation (P0.1 max,CO2). A group of six hypercapnic, less dyspnoeic (grade II to III) COPD patients (Group B), with similar mechanical characteristics, and another less obstructed historically normocapnic control group (Group C) were also considered. Before IL, in Group A VT was lower than in C, and P0.1 (%P0.1 max,CO2) was greater than in Group B and C. After a 7 day period with IL, VT increased, Rf decreased, and arterial blood gases and dyspnoea grade improved; P0.1 (%P0.1 max,CO2) significantly decreased remaining, however, greater than in Group C. In Group A the time course of arterial carbon dioxide tension (Pa,CO2) and P0.1 (%P0.1 max,CO2) were significantly related to each other. These data seem to indicate that IL is effective in improving respiratory function and symptoms in chronic hypercapnic severely dyspnoeic COPD patients. The observation that these effects were associated with a decrease in NMRD reflects an improved efficiency of the respiratory system. After IL, respiratory function in Group A was similar or even better than that in Group B. This study also considers the possibility of putting severely dyspnoeic hypercapnic COPD patients into an IL trial before starting a traditional rehabilitation programme.

Noninvasive ventilatory supports are gaining a prominent position among ventilatory techniques aimed to improve ventilation in patients with acute-on-chronic respiratory failure (ACRF). It has not yet been established whether these techniques can be considered as a preventive measure to avoid the need for endotracheal intubation, or are really another means to provide full ventilatory support. At our respiratory intensive care unit (RICU), the ventilatory treatment of ACRF has, for many years, been based on a conservative method, which relies on the use of a body ventilator (iron lung) providing intermittent negative pressure ventilation (INPV). From 1975 to 1991, we treated ACRF in 2,116 patients with chronic obstructive pulmonary disease (COPD) and 604 patients with restrictive thoracopulmonary disease (RTD). Two thousand and eleven patients (95%) underwent INPV. The mortality rate during hospitalization was 9.9% for the patients as a whole (10% and 8.9% for COPD and RTD patients, respectively). The mean length of stay in the RICU was 10.5 +/- 9.5 days. Furthermore, we report the results of our previous studies which investigated how the iron lung works, and how it affected the short- and long-term prognosis of COPD patients in ACRF. Finally, in 180 patients, we report the effects of INPV provided by iron lung on the treatment of ACRF with hypoxic hypercapnic coma (HHC). INPV resulted in a significant improvement of arterial blood gas values and pH, associated with a progressive recovery of the level of consciousness. Only 13 patients needed intubation and 41 (23%) died during hospitalization.(ABSTRACT TRUNCATED AT 250 WORDS)

Broxaterol, a new selective beta 2-agonist, has been shown to exert inotropic effects on both fresh and fatigued canine diaphragm. We evaluated the effect of broxaterol on the activation and force output of the respiratory muscles in patients with chronic obstructive pulmonary disease (COPD). We studied 9 patients with moderate to severe COPD. Each patient was infused with saline and Broxaterol (200 micrograms) in saline alternately. We measured lung volumes, maximal inspiratory pressure (MIP), maximal expiratory pressure (MEP), breathing pattern, P0.1, respiratory muscle EMG (diaphragm, EMGd, and parasternal, EMGp) and P0.1/EMGd ratio. Measurements were made under control conditions and at 15, 30, 60, and 120 min after each infusion. Broxaterol, but not saline, resulted in a slight but significant increase in vital capacity (VC), forced expiratory volume in one second (FEV1) and MIP, and a decrease in functional residual capacity (FRC). Breathing pattern did not change, while EMG significantly decreased, and P0.1/EMGd significantly increased in 5 of the 9 patients after broxaterol. These data seem to indicate that by partially unloading the respiratory muscles, broxaterol results in decreased muscle activation (EMG). Increase in chest wall neuromuscular coupling (P0.1/EMGd) may also be observed.

We studied the effect of microgravity (0 Gz) on the anteroposterior diameters of the upper (URC-AP) and lower (LRC-AP) rib cage, the transverse diameter of the lower rib cage (LRC-TR), and the xiphipubic distance and on the electromyographic (EMG) activity of the scalene and parasternal intercostal muscles in five normal subjects breathing quietly in the seated posture. Gastric pressure was also recorded in four subjects. At 0 Gz, end-expiratory LRC-AP and xiphipubic distance increased but LRC-TR invariably decreased, as did end-expiratory gastric pressure. No consistent effect was observed on tidal LRC-TR and xiphipubic displacements, but tidal changes in URC-AP and LRC-AP were reduced. Although scalene and parasternal phasic inspiratory EMG activity tended to decrease at 0 Gz, both muscle groups demonstrated an increase in tonic activity. We conclude that during brief periods of weightlessness 1) the rib cage at end expiration is displaced in the cranial direction and adopts a more circular shape, 2) the tidal expansion of the ventral rib cage is reduced, particularly in its upper portion, and 3) the scalenes and parasternal intercostals generally show a decrease in phasic inspiratory EMG activity and an increase in tonic activity.

The action on the lung of interosseous intercostal muscles located in the third and the seventh interspaces was studied in 15 anesthetized-curarized supine dogs. Changes in pleural pressure, airflow rate, and lung volume produced by maximal stimulation of both intercostal muscle layers were measured at and above functional residual capacity (FRC). In five animals measurements were also obtained during isolated stimulation of the internal layer. At FRC, intercostal stimulation in the upper interspaces had invariably an inspiratory effect on the lung but no effect was detectable in the lower interspaces. Qualitatively similar results were obtained during isolated stimulation of the internal layer. Increasing lung volume reduced the inspiratory action of the upper intercostals and conferred an expiratory action to the lower intercostals. These results indicate the following: 1) when contracting in a single interspace, the external and internal intercostals have a qualitatively similar action on the lung; and 2) this action, however, depends critically on their location along the cephalocaudal axis of the rib cage: in the upper portion of the rib cage, both muscle layers have an inspiratory effect at and above FRC; in the lower portion of the rib cage, they have no respiratory action at FRC and act in the expiratory direction at higher lung volumes.

We used a high-resolution ultrasound to make electrical recordings from the transversus abdominis muscle in humans. The behavior of this muscle was then compared with that of the external oblique and rectus abdominis in six normal subjects in the seated posture. During voluntary efforts such as expiration from functional residual capacity, speaking, expulsive maneuvers, and isovolume “belly-in” maneuvers, the transversus in general contracted together with the external oblique and the rectus abdominis. In contrast, during hyperoxic hypercapnia, all subjects had phasic expiratory activity in the transversus at ventilations between 10 and 18 l/min, well before activity could be recorded from either the external oblique or the rectus abdominis. Similarly, inspiratory elastic loading evoked transversus expiratory activity in all subjects but external oblique activity in only one subject and rectus abdominis activity in only two subjects. We thus conclude that in humans 1) the transversus abdominis is recruited preferentially to the superficial muscle layer of the abdominal wall during breathing and 2) the threshold for abdominal muscle recruitment during expiration is substantially lower than conventionally thought.

Partly phosphatized, oolitic-biogenic limestones were recovered 950–1300 m below sea level from two sites near the crest of a transverse ridge running parallel and adjacent to the Romanche fracture valley (equatorial Atlantic). Some of the biogenic contituents of the limestones (the benthonic foraminiferal genusAmphistegina; corals of the genusStylophora sp., scaphopods, etc.); their paleofacies assemblage (including echinoderms, gastropods, calcareous algae, etc.); and the presence of a well-developed oolitic facies, indicate that the limestones formed in very shallow water close to sea level. In addition, several features of the limestones (including the presence of stromatolite-like laminae, and dissolution features typical of subaerial diagenesis) suggest that the summit of the transverse ridge might have undergone episodes of emersion. The limestones were formed on a shallow carbonate bank at around the Miocene-Pliocene boundary, i.e., 5 ± 1 Myr ago, as determined by the age of fossil planktonic foraminifera and corals. The transverse ridge must have subsided since that time at an average rate of 0.2 mm/yr. It is unlikely that the vertical motions of the Romanche transverse crustal block were caused solely by accreting plate margin- or mantle plume-related volcanic and/or tectonic processes. It is suggested instead that such motions are related to vertical tectonism typical of large oceanic fracture zones.

In patients with migraine, the various sensory stimulation modalities, including visual stimuli, invariably fail to elicit the normal response habituation. Whether this lack of habituation depends on abnormal activity in the sub-cortical structures responsible for processing incoming information as well as nociception and antinociception or on abnormal cortical excitability per se remains debateable. To find out whether inducing tonic pain in the hand by cold pressure test (CPT) alters the lack of visual-evoked potential (VEP) habituation in migraineurs without aura studied between attacks we recorded VEPs in 19 healthy subjects and in 12 migraine patients during four experimental conditions: baseline; no-pain (hand held in warm water, 25 degrees C); pain (hand held in cold water, 2-4 degrees C); and after-effects. We measured P100 amplitudes from six blocks of 100 sweeps, and assessed habituation from amplitude changes between the six sequential blocks. In healthy subjects, the CPT decreased block 1 VEP amplitude and abolished the normal VEP habituation (amplitude decrease to repeated stimulation) in patients with migraine studied between attacks; it left block 1 VEP amplitude and abnormal VEP habituation unchanged. These findings suggest that the interictal cortical dysfunction induced by migraine prevents the cortical changes induced by tonic painful stimulation both during pain and after pain ends. Because such cortical changes presumably reflect plasticity mechanisms in the stimulated cortex, our study suggests altered plasticity of sensory cortices in migraine. Whether this abnormality reflects abnormal functional activity in the subcortical structures subserving tonic pain activation remains conjectural.