Non-invasive proportional assist and pressure support ventilation in patients with cystic fibrosis and chronic respiratory failure

BACKGROUND: Patients with advanced cystic fibrosis can benefit from non-invasive positive pressure ventilation (NPPV) for the treatment of acute decompensation as well as for the management of chronic respiratory failure. This study was undertaken to compare the physiological effects of non-invasive proportional assist ventilation (PAV) and pressure support ventilation (PSV) on ventilatory pattern, transcutaneous blood gas tensions, and diaphragmatic effort in stable patients with cystic fibrosis and chronic CO2 retention. METHODS: In 12 patients two periods of spontaneous breathing were followed randomly by PSV (12 (3) cm H2O) and PAV (flow assist 4.9 (1.3) cm H2O/l.s, volume assist 18.9 (5.1) cm H2O/l) set for the patient's comfort and administered for 40 minutes with 2 cm H2O continuous positive airway pressure. Ventilatory pattern, transcutaneous blood gas tensions, and surface diaphragmatic electromyography were measured in the last 10 minutes of each application. RESULTS: On average, both PSV and PAV improved ventilation (+30%), tidal volume (+30%), and transcutaneous CO2 (-7%) while reducing diaphragmatic activity (-30% with PSV, -20% with PAV). Mean inspiratory airway pressure was lower during PAV than during PSV (9.7 (1.9) and 12.9 (2.7) cm H2O, respectively; p<0.05). The mean coefficient of variation of tidal volume was about 20% (range 11-39%) during spontaneous breathing and did not change with either PAV or PSV. CONCLUSIONS: These results show that short term administration of nasal PAV and PSV to patients with stable cystic fibrosis with chronic respiratory insufficiency is well tolerated, improves ventilation and blood gas tensions, and unloads the diaphragm.     

Determinants of left ventricular systolic function recovery after an acute coronary syndrome.

INTRODUCTION: Ischemic heart disease is a major cause of heart failure in western societies. However, the factors that may influence left ventricular function (LVF) recovery after an acute coronary syndrome (ACS) are still unclear. OBJECTIVE: To identify variables that may influence LVF evolution one year after ACS. METHODS: 104 patients hospitalized with ACS between 7/1/2001 and 12/31/2002 and with systolic dysfunction--defined as an echocardiographic ejection fraction (EF) < or = 45%--were randomly allocated to a planned coronary follow-up program (FUP) or a general cardiology clinic (GC); patients from both groups were also randomly referred to a structured cardiac rehabilitation program (CRP). EF was re-assessed at one year. We compared differences between patients who recovered left ventricular function (EF > 45%; group 1) and those who did not (group 2). RESULTS: One year after discharge, 44.2% of the patients had recovered function. There were no significant differences between the groups in gender (77.7 vs. 76.5% male), age (56 vs. 59 years), hypertension, diabetes, dyslipidemia, smoking habits or family history. A previous history of cardiovascular events was more frequent in group 2 (11.1% vs. 35.3%, p = 0.03). Cardiac catheterization was performed before discharge in 88.8% and 88.2% in groups 1 and 2 respectively (p = NS); no differences were found in coronary anatomy between the two groups. Angioplasty was performed in 54.2% in group 1 and 50% in group 2 (p = NS). There were no differences in the use of angiotensin-converting enzyme inhibitors (83.3% vs. 87.5%), beta-blockers (87.5% vs. 87.5%), nitrates (37.5% vs. 33.3%), aspirin (95.8% vs. 95.8%), statins (79.1% vs. 75%) or diuretics (20.8% vs. 45.8%). There was no significant difference in LVF recovery between patients randomized to FUP or GC (38.5% vs. 54.5%). 87.5% of patients who completed the CRP had normal EF at one year compared to 32.7% of patients not referred to the program (p = 0.009). Although EF improved in both groups, this improvement was greater in patients who completed a CRP (EF 8% vs. 5%, p = 0.003). CONCLUSION: A previous cardiovascular event and completion of a CRP were the only variables that influenced LVF recovery. Thus, enrollment in a CRP, in addition to standard therapy, could be an important therapeutic measure in patients with systolic dysfunction after ACS; our data suggest that these programs should be more widely used.     

Effects of intravenous L-acetylcarnitine on retinal oscillatory potentials

L-acetylcarnitine is a compound with cholinergic properties and putative action on the visual system and the glucose metabolism. Ten healthy, emmertropic volunteers (age range: 21 to 28 years) were studied. Each subject was administered 5, 10, and 30 mg/kg acute intravenous doses of L-acetylcarnitine and matching placebo. Retinal oscillatory potentials to full-field flash stimulation were recorded before and 30, 60, and 120 min after administration. A systematic reduction of the implicit time of the P2 and N2 oscillatory potential components was observed after administration of the 10 and 30 mg/kg doses: significant changes were not evident at the 5 mg dose or after placebo. The latency reduction was significantly correlated with the postdrug increment of the L-acetylcarnitine plasma concentration. No other systematic modification in latency of amplitude was observed.The results were presented in part at the XXV I.S.C.E.V. Symposium, Sarasota (Florida), April 26–30, 1987.     

Correlation with age and sex of flash-evoked electroretinogram and retinal oscillatory potentials recorded with skin electrodes

Electroretinograms and retinal oscillatory potentials to full-field flash stimulation were recorded by dermal electrodes in a population of subjects (1 to 84 yrs) balanced for age and sex (119 females, 133 males), without evidence or history of ocular and/or relevant systemic diseases. The electroretinogram latencies and b-wave amplitude increased, while the a-wave amplitude decreased linearly with age. The oscillatory potential amplitude initially increased, to decrease approximately at the age of 50, with an inverted U-shaped distribution.Presented in part at the XXV ISCEV Symposium, Sarasota (Florida), April 26–30, 1987.     

Carvedilol protects ischemic cardiac mitochondria by preventing oxidative stress.

Ischemia negatively affects mitochondrial function by inducing the mitochondrial permeability transition (MPT). The MPT is triggered by oxidative stress, which occurs in mitochondria during ischemia as a result of diminished antioxidant defenses and increased reactive oxygen species production. It causes mitochondrial dysfunction and can ultimately lead to cell death. Therefore, drugs able to minimize mitochondrial damage induced by ischemia may prove to be clinically effective. We analyzed the effect of carvedilol, a beta-blocker with antioxidant properties, on mitochondrial dysfunction. Carvedilol decreased levels of TBARS (thiobarbituric acid reactive substances), an indicator of oxidative stress, which is consistent with its antioxidant properties. Regarding cell death by apoptosis, although ischemia did increase caspase-8-like activity, there were no changes in caspase-3-like activity, which is activated downstream of caspase-8; this may indicate that the apoptotic cascade is not activated by 60 minutes of ischemia. We conclude that carvedilol protects ischemic mitochondria by preventing oxidative mitochondrial damage, and, by so doing, it may also inhibit the formation of the MPT pore.     

Tumour necrosis factor β gene polymorphisms in myasthenia gravis

Genetic analyses indicate that genes within the major histocompatibility complex (MHC) can be involved in susceptibility to autoimmune disease. To investigate the role of the tumour necrosis factor beta (TNFB) gene in myasthenia gravis (MG) susceptibility, we analysed an NcoI polymorphism within the TNFB gene in 63 MG patients and 93 healthy individuals. When patients were subdivided according to thymic pathology, we found differences between MG patients with thymic hyperplasia and thymoma versus controls. In MG patients with thymic hyperplasia we found a positive association with the TNFB*1 allele [Relative risk (RR): 2.6; P<0.001] and phenotype (RR: 1.8; P<0.005) and a negative association with the TNFB*2/2 genotype (RR: 0.2; P<0.001) when compared to the controls. On the other hand, in MG patients with thymoma we found a positive association with the TNFB*2/2 genotype (RR: 5.6; P<0.01) and a negative association with the TNFB*1 allele (RR: 0.3; P<0.05) and *1/2 genotype (RR: 0.2; P<0.01). These data suggest that the two different forms of MG can have different pathogenesis and that the TNFB gene could influence susceptibility to MG.     

Course and treatment of myasthenia gravis during pregnancy

OBJECTIVE: To evaluate the influence of myasthenia gravis (MG) on pregnancy and potential treatment risks for infants and mothers. BACKGROUND: MG frequently affects young women in the second and third decades of life, overlapping with the childbearing years. Knowledge of the potential effects of 1) pregnancy on the course of MG and 2) the use of immunosuppressive drugs during pregnancy is limited, rendering decision-making difficult for both patient and physician. METHODS: We studied 47 women who became pregnant after the onset of MG. Immunosuppressive drugs were administered when MG symptoms were not controlled with anticholinesterases. Sixty-four pregnancies resulted in 55 children and 10 abortions. RESULTS: During pregnancy, MG relapsed in 4 of 23 (17%) asymptomatic patients who were not on therapy before conception; in patients taking therapy, MG symptoms improved in 12 of 31 pregnancies (39%), remained unchanged in 13 (42%), and deteriorated in 6 (19%). MG symptoms worsened after delivery in 15 of 54 (28%) pregnancies. Anti-acetylcholine receptor antibody (anti-AChR ab) was positive in 40 of 47 mothers and was assayed in 30 of 55 newborns; 13 were positive and 5 of 55 (9%) showed signs of neonatal MG (NMG). All affected babies were seropositive. CONCLUSIONS: Pregnancy does not worsen the long-term outcome of MG. The course of the disease is highly variable and unpredictable during gestation and can change in subsequent pregnancies. The occurrence of NMG does not correlate with either maternal disease severity or anti-AChR antibody titer. Immunosuppressive therapy, plasmapheresis, and i.v. human immunoglobulins can be administered safely if needed.