[Respiratory muscle failure in sepsis].
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Biomedical subjects
Publications and source records attributed to E Barreiro.
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BACKGROUND: A reduction in expiratory muscle (ExM) endurance in patients with chronic obstructive pulmonary disease (COPD) may have clinically relevant implications. This study was carried out to evaluate ExM endurance in patients with COPD. METHODS: Twenty three patients with COPD (FEV(1) 35 (14)% predicted) and 14 matched controls were studied. ExM endurance was assessed using a method based on the use of an expiratory threshold valve which includes two steps. In step 1 the load is progressively increased (50 g every 2 minutes) until task failure is reached, and the pressure generated against the highest tolerated load is defined as the maximal expiratory sustainable pressure (Pthmax). In step 2 subjects breathe against a submaximal constant load (80% of Pthmax) and the time elapsed until task failure is termed the expiratory endurance time (Tth(80)). In addition, the strength of peripheral muscles (handgrip, HGS) and respiratory muscles (maximal inspiratory and expiratory pressures, PImax and PEmax, respectively) was evaluated. RESULTS: Patients with COPD had lower ExM strength and endurance than controls: PEmax 64 (19)% predicted v 84 (14)% predicted (mean difference 20%; 95% confidence intervals (CI) 14 to 39); Pthmax 52 (27) v 151 (46) cm H(2)O (mean difference 99, 95% CI 74 to 123); and Tth(80) 9.4 (6.3) v 14.2 (7.4) min (mean difference 4.8, 95% CI 1.0 to 10.4; p<0.01 for all). Interestingly, ExM endurance directly correlated with both the severity of airways obstruction (Pthmax with FEV(1), r=0.794, p<0.01) and the reduction in strength observed in different muscle groups (Pthmax with HG, PImax or PEmax, r=0.550, p<0.05; r=0.583, p<0.001; and r=0.584, p<0.001, respectively). CONCLUSIONS: ExM endurance is decreased in patients with COPD. This impairment is proportional to the severity of the disease and is associated with lower strength in different muscle groups. This suggests that systemic effects are implicated in the impairment observed in ExM function.
Three ataxia telangiectasia (AT) patients have been characterized immunologically and molecularly. Patient 1 presents two nondescribed splicing mutations which affect exons 15 and 21 of the ATM gene. The maternal defect consists of a G > A transition in the first nucleotide of the intron 21 donor splicing site which results in a complete deletion of exon 21. The paternal mutation consists of an A > C transversion in the intron 14 acceptor splicing site which produces a partial skipping of exon 15. Two abnormal alternative transcripts were found, respectively, 17 and 41 nucleotides shorter. Patient 2 presents a homozygous genomic deletion of 28 nucleotides in the last exon of the gene. This deletion changes the normal reading frame after residue 3003 of the protein and introduces a premature stop codon at residue 3008 that could originate a truncated ATM protein. Patient 3, a compound heterozygote, presents a defect which consists of a G > A transition in the first nucleotide of intron 62 donor splicing site which results in a complete deletion of exon 62. The results obtained during a three year period in the proliferation assays show an impaired PMA (phorbol myristate acetate) activation in specific T lymphocyte activation pathways (CD69, CD26, CD28, CD3, PHA, PWM and Con A mediated) but not in others (CD2, ionomycin, and Ig surface receptor). The possible link among specific ATM mutations and abnormal immune responses is unknown.
Our objective was to develop an in vivo model to study the timing and mechanisms underlying diaphragm injury and repair. Diaphragm injury was induced in anesthetized rats by the application of a 100 mM caffeine solution for a 10-min period to the right abdominal diaphragm surface. Diaphragms were removed 1, 4, 6, 12, 24, 48, 72, and 96 h and 10 days after the injury, with contractile function being assessed in strips in vitro by force-frequency curves. The extent of caffeine-induced membrane injury was indicated by the percentage of fibers with a fluorescent cytoplasm revealed by inward leakage of the procion orange dye. One hour after caffeine exposure, 32.9 +/- 3.1 (SE) % of fibers showed membrane injury that resulted in 70% loss of muscle force. Within 72-96 h, the percentage of fluorescent cells decreased to control values. Muscle force, however, was still reduced by 30%. Complete muscle strength recovery was observed 10 days after the injury. Whereas diaphragmatic fiber repair occurred within 4 days after injury induction, force recovery took up to 10 days. We suggest that the caffeine-damaged rat diaphragm is a useful model to study the timing and mechanisms of muscle injury and repair.
In this study we evaluated the role of the neuronal nitric oxide synthase (nNOS) in lipopolysaccharide (LPS)-induced diaphragmatic contractile dysfunction and sarcolemmal injury. Wild-type (WT) mice or mice deficient in the nNOS gene (nNOS(-/-)) were injected with either saline (control) or Escherichia coli LPS (LPS groups) and sacrificed 12 h later. The diaphragm was then examined for NOS expression, NOS activity, and in-vitro contractility. We also assessed sarcolemmal injury in isolated muscle strips under resting condition and after 3 min of artificial stimulations. In WT mice, LPS injection reduced maximum force to about 75% of that of control animals and raised total NOS activity significantly due to the induction of the iNOS isoform. Although muscle fiber injury was minimal under resting condition, the percentage of injured fibers in control and LPS-injected mice approached 27% and 40% of total fibers, respectively, in response to artificial stimulation. By comparison, LPS injection in nNOS(-/-) mice elicited a worsening of muscle contractility (maximum force < 60% of control animals) but elicited degrees of sarcolemmal injury similar to those observed in the WT animals. In addition, muscle NOS activity and iNOS protein level in nNOS(-/-) mice injected with LPS reached about 10% and 60% of that of WT animals, respectively (p < 0.05 compared with WT animals). Protein level of endothelial NOS isoform in the diaphragm was not altered by LPS injection in either WT or nNOS(-/-) animals. We conclude that nNOS plays a protective role in attenuating the negative influence of sepsis on diaphragmatic contractility but is not involved in the pathogenesis of sepsis-induced sarcolemmal injury.
This review focuses on the structural and functional changes occurring in respiratory as well as peripheral muscles in COPD patients. These changes are particular for each muscle territory or compartment. Respiratory muscles predominantly undergo structural adaptive changes. However, they have to do their job in unfavourable mechanical conditions and thus their function is impaired. Peripheral muscles have to be grouped in at least two different compartments: upper and lower limb muscles. The structure and function are relatively preserved in the former, due to the maintenance of some daily activities involving the arms or even the use of some of these muscles in the ventilatory effort. Lower limb muscles in contrast undergo involute structural changes which result in an impairment in their function and in the global exercise capacity of the individual. Deconditioning due to a reduction in daily activities secondary to ventilatory impairment is probably the driving factor for these changes. Although the level of activity appears to be the main determining factor in changes occurring in different territories, this would be modulated by other local and systemic factors, such as inflammation, oxidative stress, drugs and nutritional abnormalities.
UNLABELLED: Bronchial asthma is a chronic disease whose prevalence and severity is increasing. Appropriate treatment of exacerbation seems to affect the subsequent course of disease. OBJECTIVES: To assess the extent of application of guidelines for treating exacerbations of asthma and to describe the clinical and epidemiological characteristics of patients. PATIENTS AND METHODS: All patients presenting with exacerbations to the emergency room of a referral hospital in a semi-rural area of Catalonia were enrolled consecutively. We recorded symptoms, function and treatment variables during the emergency and when the patient was stable, at which time we also administered the Asthma Quality of Life Questionnaire (AQLQ). RESULTS: Forty-seven percent of patients resided in rural villages. Seventy-one percent lived in the area served by our hospital. Of the remaining patients, 57% came from municipalities in the Baix Empordà area, 29% in Alt Empordà area and 14% in La Selva area. Seventy-one percent went to the hospital directly from home, 66% of them were in the province of Girona; 75% of those homes were within urban areas. Of the 29% who had been sent to the emergency room by a physician, 71% were from a rural area. The 119 asthma exacerbations treated (114 patients, 71 females, 42 +/- 23 years) accounted for 0.3% of all emergency room visits. The exacerbation was considered severe in 31%, moderate in 47% and mild in all remaining cases. Eighty-eight percent of patients had experienced an exacerbation before. Symptoms were often present before the attack, but nearly half the patients were receiving relatively inadequate medication. Peak expiratory flow and oxygen saturation were recorded in 70% of cases and both variables improved after initial treatment (250 +/- 97 to 349 +/- 92 l/min, p < 0.001; and 92 +/- 7 to 96 +/- 2%, p < 0.01, respectively). All patients received inhaled salbutamol, 44% inhaled corticosteroids and 73% intravenous corticosteroids. A quarter of the patients were admitted to the ward (0.4% of all admissions) and 4% were admitted to the intensive care unit. Patients stayed 8.8 +/- 1.4 h in the emergency room. When patients were stable, asthma was severe in 14%, moderate in 42%, mild but persistent in 27%, and occasional in 17%. The total score on the AQLQ was 13.8 +/- 11.1, with mood being the dimension with the highest score (5.1 +/- 4.9). This score, along with social restriction, were lowest in the group of patients with chronic airflow obstruction. CONCLUSIONS: Nearly half the patients were from rural villages most of which were located outside the zone served directly by our hospital. The preference for specialized medical attention would explain the percentage of patients seen who did not belong to the assigned area. Difficulty of access to the hospital from certain rural areas would account for the greater number of rural patients who had been referred by a physician. Clinical management and monitoring of asthmatic patients with exacerbation could be improved by greater diffusion and application of guidelines. It would be interesting to incorporate come sort of questionnaire on quality of life while taking a patient's history.
UNLABELLED: Noteworthy among breathing training techniques is so-called diaphragmatic breathing. In spite of the technique's name, however, little is known of the functional characteristics of this ventilatory method. OBJECTIVE: To asses the mechanics of respiratory muscles, particularly diaphragm muscles, during diaphragmatic breathing in patients with severe chronic obstructive pulmonary disease (COPD). METHODS: Ventilatory pattern and respiratory pressures (abdominal [Pga], intrathoracic [Pes] and transdiaphragmatic [Pdi]) were studied in 10 patients with severe COPD in stable phase (age 69 +/- 6 years, FEV1 33 +/- 12% ref) at baseline and during deep breathing with spontaneous muscle recruitment (SMR) and during breathing training. Measurements were taken with the patient seated and in supine decubitus position. RESULTS: In seated position ventilatory pattern was similar with SMR and during breathing training. Mean Pdi during airflow, however, was greater during breathing training than with SMR (34.8 +/- 8.0 and 29.3 +/- 9.3 cmH2O, respectively, p < 0.05) for similar levels of Pes. Mechanical effectiveness of the diaphragm expressed as Vt/Pdi) was less during breathing training, however (36.1 +/- 10.4 and 49.5 +/- 15.8 cc/cmH2O, p < 0.05), with no changes in overall efficacy of respiratory muscles (Vt/Pes). In supine decubitus position, ventilatory patterns of SMR and breathing training were similar, although Vt and T1 were slightly higher in the latter (1,065 +/- 305 vs. 1,211 +/- 314 cc, p < 0.01; and 2.76 +/- 1.32 vs. 3.07 +/- 1.23 sec, p < 0.05). Pdi was also higher during breathing training (29.7 +/- 10.2 and 38.0 +/- 10.5 cmH2O, p < 0.05), although accompanied in this case by a higher Pes (21.2 +/- 7.5 to 26.4 +/- 8.4 cmH2O, p < 0.005). In supine decubitus position, the effectiveness of both diaphragm muscles and respiratory muscles overall was similar for both ventilatory modes. CONCLUSIONS: Breathing training truly involves greater use of the diaphragm, both in seated and supine decubitus positions. Breathing training does not provide greater ventilatory efficacy than SMR, however, in COPD patients.
There is little information available concerning the extent to which chronic obstructive pulmonarv disease (COPD) patients are satisfactorily managed, especially, regards factors supposedly related to COPD exacerbation. The present study assessed the prevalence rates of potentially modifiable risk factors of COPD exacerbation in patients hospitalized for this reason. A systematic sample of one out of two patients admitted for COPD exacerbation, during 1 yr, in four tertiary hospitals in the Barcelona area, Spain, was performed. Patients answered a questionnaire and underwent anthropometric measurements, spirometric tests and arterial blood gas sampling. Prevalence rates and 95% confidence intervals (95% CI) for risk factors were obtained, and the generalized estimating equation (GEE) method was used to allow for patients to provide information on different admissions. The study recruited 353 patients (29 female) with a total of 404 admissions age (mean+/-SD) 69+/-9, median forced expiratory volume in one second (FEV1) 31% of predicted and mean partial pressure of oxygen (PO2) 63+/-13 mmHg. Of these, 28% had not received an influenza vaccination; a high number (86%) did not attend rehabilitation programmes; 28% of patients with PO2 < or =55 mmHg were not using long-term oxygen therapy (LTOT); among LTOT users, 18% used it <15 h a day; 43% of the total failed in some of the essential inhaler manoeuvres; 26% were current smokers; 21% of noncurrent smokers were exposed to passive smoking at home; current occupational exposure was low (5%). In summary, the authors found a moderate to high prevalence of potentially modifiable risk factors in a large representative sample of patients hospitalized for a chronic obstructive pulmonary disease exacerbation, suggesting unsatisfactory features in their management.
UNLABELLED: Ventilatory requirements increase during exercise. The respiratory muscles of patients with chronic obstructive pulmonary disease (COPD) are at a particular disadvantage when dealing with such increased demand. The objective of this study was to evaluate the changes in respiratory muscles brought on by exercise in such patients. METHODS: Twelve patients with severe CFOPD (FEV1 < 50% ref., 63 +/- 7 years) were enrolled. Breathing patterns and esophageal (Pes and transdiaphragmatic (Pdi) pressures and SaO2 were measured during submaximal exercise/Ecsbmax, 60% of the maximum tolerated load). A sniff maneuver was performed with the patients breathing ambient air with added oxygen to achieve 99% SaO2. We also measured level of FRC by inductive plethysmograph in a subgroup of five patients. RESULTS: During EXsbmáx, SaO2 decreased (from 95.0 +/- 2.1 to 92.3 +/- 4.0%; p < 0.01); Vt increased (717 +/- 199 to 990 +/- 297 cc, p < 0.01), as did respiratory rate (RR, 17 +/- 6 a 28 +/- 9; p < 0.01). Pes and Pdi were greater at Vt, changing from -12.4 +/- 4.8 to -27.0 +/- 10.1 and 16.6 +/- 6.1 to 30.4 +/- 12.4 cmH2O, respectively (p < 0.01 in both cases), whereas no significant changes were observed for maximal effort (Pesmax, -61.4 +/- 16.5 cersus -65.9 +/- 15.2 cmH2O; Pdimac 89.7 +/- 26.1 versus 81.7 +/- 35.7 cmH2O). Used as a global measure, Pdi/Pdimáx worsened (0.21 +/- 0.12 a 0.42 +/- 0.20; p < 0.01), as dud the diaphragm tension-time (TTdi; 0.07 +/- 0.04 to 0.15 +/- 0.06, p < 0.01). Intrinsic positive end-expiratory pressure (PEEPi) increased an estimated 2.7 +/- 2.1 to 9.4 +/- 5.8 cmH2O (p < 0.001), while FRC (delta 357 +/- 274 ml). Durante el EXsbmáx with oxygen supplementation, SaO2 did not decrease. However supplementation, though Ti/TTOT and maximal pressures remained unchanged. CONCLUSIONS: Respiratory muscle function changes induced by Exsbmáx seem to relate mainly to a worsening of system mechanics.
A 7-month-old girl was diagnosed with acute megakaryoblastic leukemia and, at the time of diagnosis, the karyotype was 48-50,XX,+4,+5,del(5)(p13),del(6)(q14), +8,inv(8)(p23.1q13),der(13) t(13;?;?),+19,-20,+21,+22,+mar [cp20]. At relapse, there was clear evidence of her constitutional status as a carrier of the pericentric inversion (8)(p23.1q13). It was a familial inversion affecting the patient's maternal lineage; a history of cancer and bleeding anomalies in carriers of the inversion led us to consider their nonrandom association with these pathologies.
Chromosomal studies in CLL have yielded poorer results than in other blood diseases because of the low mitotic index of the B cells. The FISH technique is a very useful tool for trisomy 12 detection in interphase nuclei in CLL, although this method cannot be a substitutive for conventional cytogenetics. The FISH technique was applied in two cases of CLL by means of satellite DNA probing specific for chromosome 12 according to the Oncor S 1370-CF kit protocol. Trisomy 12 was detected, along with other chromosomal abnormalities secondary to this trisomy. Both patients had lymphocyte counts lower than 5.0 x 10(9)/L and their peripheral blood immunophenotype showed 58% lymphocytes with lambda sIg of medium density, co-expressing CD5 and unable to form rosettes with mouse red-cells. Patient no. 1 was 46,XY/47,XY + 12/47,XY + 12,5q-, and patient no. 2 was 46,XX/47,XX + 12,14q-. The presence of secondary anomalies could explain the special clinico-haematological picture, characterised by low lymphocytosis and presence of irregular nuclei in mature lymphocytes, along with the lack of CD23 expression and rosette formation with mouse red-cells. FISH technique combined with chromosome analysis may prove a useful means for diagnosing and recognising variants or specific entities within low-grade lymphoproliferative syndromes.
The myelodysplastic syndromes (MDS) are a heterogeneous group of diseases with different prognosis and evolution. Most of the studies on prognostic factors performed previously have independently evaluated the clinico-hematologic or cytogenetic data at diagnosis. In the present paper, 46 primary MDS were clinically, hematologically, and cytogenetically investigated at diagnosis, in order to determine the principal factors affecting the survival probability between a great number of characteristics. A univariate regression analysis of all the data allows one to recognize that the main factors are: the complexity of karyotype (p = 0.00001), the percentage of type I and total marrow blast cells (p = 0.001), and the abnormal localized immature myeloid precursors' (ALIP) presence (p = 0.001). Twenty-five patients underwent consecutive studies during their evolution. The karyotype instability gives information both on the likely evolution to acute leukemia and on poor survival.
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A two month old boy with multiple malformations: mental retardation, microcephaly, hyperterloism, displasic ears, hypospadias, unilateral cryptorchidism and holoprosencephaly is presented. In leukocytes culture, patient shows a deletion of the short arm of a 18 chromosome. This aberration apears "de novo" in this patient.
Twenty cases of Turner's syndrome are presented. Ten cases showed cariotype XO, nine XO/XX and one case showed mosaicism with three cell lines one of which showed a ring chromosome (XO/XX/XXr). The clinical characteristics of syndrome and the associated malformations are appraised. Commentaries are made about ultimate height attained by this patients.