Last 3 months of life in home-ventilated patients: the family perception.

We studied the family's perception of care in patients under home mechanical ventilation during the last 3 months of life. In 11 respiratory units, we submitted a 35-item questionnaire to relatives of 168 deceased patients exploring six domains: symptoms, awareness of disease, family burden, dying, medical and technical problems. Response rate was 98.8%. The majority of patients complained respiratory symptoms and were aware of the severity and prognosis of the disease. Family burden was high especially in relation to money need. During hospitalisation, 74.4% of patients were admitted to the intensive care unit (ICU). 78 patients died at home, 70 patients in a medical ward and 20 in ICU. 27% of patients received resuscitation manoeuvres. Hospitalisations and family economical burden were unrelated to diagnosis and mechanical ventilation. Families of the patients did not report major technical problems on the use of ventilators. In comparison with mechanical invasively ventilated patients, noninvasively ventilated patients were more aware of prognosis, used more respiratory drugs, changed ventilation time more frequently and died less frequently when under mechanical ventilation. We have presented good points and bad points regarding end-of-life care in home mechanically ventilated patients. Noninvasive ventilation use and diagnosis have impact on this burden.

Elevated static compliance of the total respiratory system: early predictor of weaning unsuccess in severed COPD patients mechanically ventilated.

OBJECTIVE: To assess in a group of COPD patients mechanically ventilated for an episode of acute respiratory failure the respiratory mechanics with a simple and non invasive method at the bedside in order to evaluate if these parameters may be predictive of weaning failure or success. DESIGN: A prospective study. SETTING: Intensive care and intermediate intensive care units. PATIENTS: 23 COPD patients ventilated for acute respiratory failure and studied within 24 hours from intubation. METHODS: Using end-expiratory and end-inspiratory airway occlusion technique, we measured PEEPi, static compliance of the respiratory system (Crs, st) maximum respiratory resistance (Rrsmax) and minimum respiratory resistance (Rrsmin). MEASUREMENTS AND RESULTS: The weaned group (A) and the not weaned group (B) were not different regarding to static PEEPi (group A 8.5 +/- 4.0 vs group B 8.9 +/- 2.6 cmH2O), TO Rrsmax (22.4 +/- 5.3 versus 22.2 +/- 9.0 cmH2O/1/s) and to Rrsmin (17.6 +/- 5.5 versus 17.9 +/- 8.0 cmH2O/1/s), while a significant difference (p < 0.001) has been found in Cst, rs (62.7 +/- 17.% versus 111.6 +/- 18.0 ml/cm H2O). The threshold value of 88.5 ml/cmH2O was identified by discriminant analysis and provided the best separation between the two groups, with a sensitivity of 0.85 and a specificity of 0.87. CONCLUSION: Cst, rs measured non invasively in the first 24 h from intubation, provided a good separation between the patients who were successfully weaned and those who failed.

Respiratory muscle fatigue does not limit exercise performance during moderate endurance run.

The role of respiratory muscle fatigue in limiting exercise performance in well-trained subjects is still controversial, especially as far as relatively short runs are concerned. To determine the occurrence of respiratory muscle impairment, we studied six well-trained athletes before, during (middle of the run) and after a 17 km run. They were all asked to produce the maximum effort they could during the race. Strength was assessed by measuring maximal inspiratory mouth pressure against close airways (MIP), dynamic lung volumes were monitored using a spirometer. No changes in forced vital capacity (FVC), maximal expiratory flow (PEF) and forced expiratory volume in 1 sec (FEV1) were observed throughout the experiment. This suggested that functional residual capacity and subsequently the initial length of respiratory muscle were unchanged. Respiratory muscle strength did not significantly vary at the different time of measurements (154.8 +/- 20.9 cm H2O at the beginning, 157.5 +/- 23.7 cm H2O after 7.5 km, 155.8 +/- 22.5 cm H2O at the end and 152.3 +/- 17.6 cm H2O after 30 min of recovery). We therefore conclude that respiratory muscle fatigue does not impair the exercise performance of well-trained athletes in a relatively short race. The difference between these results and others reported in literature, could be explained by the different degree of training of the subjects performing the race.

Ventilatory techniques during weaning.

Ventilatory techniques are only a part of the weaning process, that also includes medical therapy, physiokinesitherapy, nutrition, psychological support and nursing. Traditional ventilatory techniques used in weaning are: T-piece trials (alternated with assist-control ventilation (ACV)), pressure support ventilation (PSV), intermittent mandatory ventilation (IMV) and continuous positive airway pressure (CPAP) ventilation. None of these techniques has been demonstrated to be better than the others, and the physician must be prepared--to try alternate strategies according to the kind of patient. Noninvasive mechanical ventilation (NIMV) can be successfully used in weaning from invasive mechanical ventilation. Furthermore, NIMV by nasal or facial mask has been successfully used in the treatment of acute respiratory failure (ARF) due to various pathologies. In these cases, the weaning trial has an immediate beginning, since noninvasive ventilation is performed alternatively with spontaneous breathing after the early phase of ARF.

Weaning and outcome from mechanical ventilation.

Weaning means the ability of a patient to breath spontaneously after mechanical ventilation. In chronic obstructive pulmonary disease (COPD) patients, inability to tolerate discontinuation of mechanical ventilation is reported to have an incidence of 25-60%. It is, therefore, important to employ simple parameters able to predict weaning success, since, in the case of failure, the validation of predictive indices of weaning may also contribute to the decision of whether or not these patients should eventually enter a programme of home ventilation. Among other indices employed, respiratory frequency/tidal volume (f/VT) ratio, compliance, rate, oxygenation and pressure (CROP) index, mouth occlusion pressure (P0.1) and static compliance of the respiratory system have been shown to be quite accurate. The survival at one year of these patients requiring mechanical ventilation ranges 34-49%. Indeed, there is a particular subset of COPD patients in whom mechanical ventilation is prolonged due to the severity of their pathology. We studied 42 of these patients requiring mechanical ventilation for more than 21 days, to assess with simple parameters (arterial blood gases, pulmonary function tests, respiratory muscle force, P0.1, nutritional status) their potential for weaning and their survival at 2 yrs. Using discriminant analysis, and employing an equation comprising maximal inspiratory pressure (MIP) and arterial carbon dioxide tension (PaCO2), we were able to predict the patients able or unable to be weaned with an accuracy of almost 85%.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of long-term therapy with oral steroids on respiratory muscle function and ventilatory drive.

It has been shown that chronic oral steroid therapy (ST) does not induce respiratory muscle dysfunction in normal and asthmatic subjects. As corticosteroids are sometimes chronically used in the treatment of the patients with chronic obstructive pulmonary disease (COPD), the aim of our study was to verify whether ST could cause respiratory muscle impairment and, since ST also affects the central nervous system, whether ST could influence the ventilatory pattern. We retrospectively studied 12 COPD patients (group A), on long-term therapy (for at least 4 consecutive months, range 4-18 months) with an oral steroid, deflazacort, 15 mg.d-1. The subjects were strictly matched, with regard to age, sex, height, weight, forced expiratory volume in one second (FEV1), residual volume (RV), arterial oxygen tension (PaCO2), arterial carbon dioxide tension (PaCO2) and pH, with 12 COPD patients (Group B) who had never taken oral steroids. To assess respiratory muscle strength, we measured maximal inspiratory (MIP) and expiratory (MEP) pressures, while mouth occlusion pressure (P0.1) was employed to assess neuromuscular drive; ventilatory pattern and airway impedence were also evaluated. Effectiveness of ST was confirmed by the plasmatic levels of endogenous cortisol. No significant differences were observed between the two groups with regard to MIP (A 72.2 +/- 9.7 vs B: 70 +/- 7.2 cmH2O) and MEP (A 91.6 +/- 10.5 vs B 94.4 +/- 7.6 cmH2O) whilst P0.1 was significantly higher in group A (2.6 +/- 0.3 cmH2O) than in group B (1.8 +/- 0.1 cmH2O). No significant differences were found among all the ventilatory parameters, but the impedence was significantly higher in group A.(ABSTRACT TRUNCATED AT 250 WORDS)

[Orthostatic hypotension in the elderly]. / L'ipotensione ortostatica nell'anziano.

The physiological answer to the orthostatic stress and changes in the elderly are examined. Moreover therapy of orthostatic hypotension, either pharmacological or not is reviewed.

Bilateral simultaneous femoral neck fracture mimicking abdominal pain in a cerebral palsy patient.

Simultaneous bilateral femoral neck fractures are unusual lesions, generally associated with an underlying condition which causes impaired bone mineralization, triggered by an increased bone stress. We present a 24-year-old cerebral palsy patient, who was previously evaluated in another institution due to inability to walk, interpreted as abdominal pain. No alteration in blood analysis or abdominal X-rays was found. As no response to treatment was observed, a new abdominal X-ray was taken, which incidentally depicted bilateral medial femoral neck fracture. He was referred to our practice after a resection arthroplasty was offered in another institution. After admission, bilateral one-stage THA was performed. Several reports emphasize bone disease as a major precipitating factor, and there is an increased incidence of hip fractures in chronic epilepsy, renal osteodystrophy, and chronic steroid use. Femoral head resection has been proven to be effective in immobilized patients, whereas this was not a reasonable option in this patient who presented walking ability. Despite the treatment election, primary care physicians should be aware of and alert to the possibility of fractures in patients with neurological disorders and calcium metabolism alterations. Late diagnosis of orthopedic injuries in this type of patients may lead to permanent disability.

The tension-time index of the diaphragm revisited in quadriplegic patients with diaphragm pacing.

The fatigue threshold of the human diaphragm, index of its endurance and fatigability, corresponds, during spontaneous breathing, to a tension-time index (TTdi = Pdi/Pdimax x T1/Ttot (i.e., the inspiratory time over the total breath duration) of 0.15 to 0.18. We studied three quadriplegic patients with diaphragm pacing in order to reassess this threshold in patients in whom the contribution of the other respiratory muscles is lacking. Transdiaphragmatic pressure (Pdi) was obtained from the difference between gastric (Pga) and esophageal (Pes) pressures while the electromyograms (EMG) of both hemidiaphragms were recorded with surface electrodes. Four runs at different TTdi were performed on different days in each subject, varying either the Pdi developed per breath, changing the frequency of stimulation, or the T1/Ttot. The time of fatigue was defined when Pdi decreased during the trials by 35% from baseline. No evidence of transmission fatigue (i.e., decline in action potential amplitude) was observed. The TTdi at which fatigue occurred in all the quadriplegic patients was around 0.10 to 0.12, well below the values previously described. After fatigue had occurred, the force recovery during the force-frequency curve was not complete after 2 h at low frequencies, whereas at high frequencies it was fully complete at 30 min. We conclude that when respiration is accomplished only by the diaphragm, without the contribution of the other respiratory muscles, the fatigue threshold is lower than previously reported.

[Factors determining the successful weaning of patients with "difficult weaning"]. / Fattori determinanti il successo dello svezzamento in pazienti con "svezzamento difficile".

OBJECTIVE: Weaning from mechanical ventilation is often possible in the most of patients, even if sometimes it is very difficult. For example, 25-53% of COPD patients cannot be weaned. The different modalities used do not justify this. The aim of the study was the evaluation of a further weaning trial in tracheotomized patients who underwent mechanical ventilation for at least 15 days in several ICU and in whom several attempts of weaning failed. DESIGN: A retrospective study (January 1993-February 1995). SETTING: Intermediate Intensive Respiratory Care Unit of Centro Medico Di Montescano. PATIENTS: Thirty-nine patients (29 male; 26 COPD, 3 post-surgery respiratory failure, 5 restrictive diseases, 4 with cardiovascular failure and 1 neurological disease) who had been tracheotomized and undergoing mechanical ventilation from at least 15 days. An initial evaluation in which respiratory mechanics and echocardiography were performed was made and then they underwent further weaning trials based on progressive decrease of the level of pressure support and periodic disconnection from MV and on medical therapy and strong physiokinesitherapy. RESULTS: Twenty-six out of 39 patients (66%) could reach definitive weaning (COPD 65%, post-surgery respiratory failure 66%, restrictive 60%, cardiovascular failure 100%, neurological disease 0%) after 17 days of average time of ventilation (range from 4 to 90). Among the important factors in determining a difficult or impossible weaning there are: a) previous wrong ventilation settings 8/26; b) cardiovascular problems 7/26; c) alterations in respiratory mechanics 2/26; d) previous excessive sedation 2/26; e) uncorrect timing of disconnection 2/26; f) poor physiokinesitherapy 2/26; g) unknown causes 3/26. Also the ICU from which the patients has been transferred plays an important role. CONCLUSIONS: The conclusion is drawn weaning from mechanical ventilation can be reached also in a part of those patients who are thought not weanable with a further, prolonged and expensive weaning trial.

Effect of salbutamol and inhaled sodium cromoglycate on the airway and neutrophil chemotactic activity in "fog"induced bronchospasm.

To investigate whether salbutamol and sodium cromoglycate (SCG) inhibit airway response and the associated mediator release induced by ultrasonic nebulation of distilled water (UNDW, "fog"), we measured the serum neutrophil chemotactic activity (NCA) during bronchial challenge with "fog" with and without premedication with placebo, salbutamol, or SCG in 10 subjects with asthma, in four sets of studies. To assess changes in airway caliber, we measured FEV1. To assess changes in NCA, we measured the maximal distance reached by neutrophils in a filter when neutrophils were challenged with the subject's serum in a Boyden chamber. Treatment with placebo did not change baseline FEV1 or serum NCA; however, FEV1 decreased and serum NCA increased (p less than 0.05) after inhalation of "fog". Treatment with SCG did not affect either FEV1 and baseline serum NCA. After inhalation of "fog", no significant bronchoconstriction nor NCA increase was observed in eight of 10 patients with maximal mean percent decrease in FEV1 of -4.26, SEM 0.99, and maximal mean percent increase in NCA of +8.6, SEM 5.28. In the two patients who developed a bronchoconstriction after challenge with SCG pretreatment, an associated significant increase in NCA was observed but did not affect baseline NCA. After inhalation of "fog", no significant decrease in FEV1 (maximal mean percent decrease FEV1, -6.71, SEM 0.17) nor significant increase in serum NCA (maximal mean percent increase NCA, +3.6, SEM 7.1) was observed in nine of 10 patients. After salbutamol, only one patient developed a bronchoconstrictive response to "fog" associated with a significant increase in serum NCA. These results suggest that both SCG and salbutamol may prevent the bronchoconstriction induced by "fog" by inhibiting mediator release.

Evidence of acute diaphragmatic fatigue in a "natural" condition. The diaphragm during labor.

Acute diaphragmatic fatigue has been experimentally shown to occur in normal healthy subjects and in patients with chronic obstructive pulmonary disease by asking them to modify their pattern of breathing or to breathe against high inspiratory resistances. During the expulsive period of labor women are asked periodically to make strong expulsive efforts and to sustain them isometrically for many seconds; this is likely to produce "natural" diaphragmatic fatigue. To investigate whether this was the case, six women were studied in the delivery room from the moment of the rupture of the amnion until delivery of the infant occurred. The development of diaphragmatic fatigue was assessed both by measuring the static maximal inspiratory pressure (MIP) and by analyzing the electromyographic power spectrum of the diaphragm (H/L ratio). The majority of contractions were concentrated in the expulsive period of labor. MIP, recorded in the supine position, significantly decreased from 103.2 +/- 17.2 cm H2O (at the beginning of the expulsive period) to 73.8 +/- 10.1 cm H2O (after the delivery). The H/L ratio fell progressively during the expulsive period; after the delivery, it was 59.2 +/- 15.7% of the value recorded at the beginning of the expulsive period. This study demonstrates that (1) the diaphragm is active in the expulsive efforts during labor and (2) the tension developed and the time each contraction is maintained may lead to the development of diaphragmatic fatigue. Therefore, we provide evidence of acute diaphragmatic fatigue in a natural condition.

Survival and prediction of successful ventilator weaning in COPD patients requiring mechanical ventilation for more than 21 days.

We studied survival and failure or success of weaning from mechanical ventilation (MV) in 42 consecutive chronic obstructive pulmonary disease (COPD) patients requiring prolonged MV (more than 21 days) after an episode of acute respiratory failure requiring admission to our Intermediate Intensive Care Unit (IICU). Parameters including arterial blood gases, pulmonary function tests, respiratory muscle force, neuromuscular drive, and nutritional status were recorded during a phase of clinical stability, in order to identify the features related to survival and weaning. All the patients were submitted to a comprehensive rehabilitation programme. Successful weaning from MV was defined as complete respiratory autonomy for at least 48 h. Twenty three patients were successfully weaned from MV after an average period of 44 days (Group A), requiring no further MV during their stay in hospital, whilst the remaining 19 patients were not able to be disconnected from the ventilator (Group B). The discriminant analysis showed that weaning from MV was significantly associated with arterial carbon dioxide tension (PaCO2), neuromuscular drive (P0.1), maximal inspiratory pressure (MIP), arterial oxygen tension (PaO2), the ratio of respiratory frequency to tidal volume (f/VT) and the serum protein level. Other pulmonary function tests (forced expiratory volume in one second (FEV1), FEV1/forced vital capacity (FVC), anthropometric data, nutritional status, number of pulmonary exacerbations during MV and evidence of cor pulmonale, were similar in the two groups. The discriminant equation considering PaCO2 and MIP could separate the two groups with an accuracy of 84%. The overall survival at 2 yrs was 40%; in Group B it was significantly lower than in Group A (22 vs 68%). Most of the deaths occurred within the first 120 days after intubation.(ABSTRACT TRUNCATED AT 250 WORDS)

The maize WD-repeat gene ZmRbAp1 encodes a member of the MSI/RbAp sub-family and is differentially expressed during endosperm development.

Members of the MSI/RbAp sub-family of WD-repeat proteins are widespread in eukaryotic organisms and form part of multiprotein complexes that are involved in various biological pathways, including chromatin assembly, regulation of gene transcription, and cell division. In this study we report the isolation and characterization of a cDNA sequence from Zea mays, which encodes an RbAp-like protein (ZmRbAp1) that binds acetylated histones H3 and H4 and suppresses mutations that have a negative effect on the Ras/cAMP pathway in yeast. The ZmRbAp genes form a gene family and are expressed in different tissues of Z. mays L. plants. Determination of its expression pattern during maize seed development revealed that ZmRbAp transcripts are abundant during the initial stages of endosperm formation. In addition, the transcripts are specifically localized in shoot apical meristem and leaf primordia of the embryo. A possible role for the ZmRbAp genes in early endosperm differentiation and plant development is discussed.

Morfologia e desenvolvimento de Schistosoma mansoni Sambon, 1907 em infeccoes unissexuais experimentalmente produzidas no camundongo. / Morphology and development of Schistosoma mansoni Sambon, 1907 in unisexual infections experimentally induced in mice

Estudou-se o desenvolvimento de Schistosoma mansoni em infeccoes unissexuais no camundongo. Os esquistossomos femeos apresentaram-se menos desenvolvidos do que os machos. Houve correlacao entre o comprimento dos machos e o numero de testiculos. Verificou-se que o isolamento sexual e prejudicial aos dois sexos, principalmente a femea