Indocyanine green angiography in choroidal tuberculomas.
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Biomedical subjects
Publications and source records attributed to T Similowski.
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BACKGROUND: The role of inhaled corticosteroids in the long term management of chronic obstructive pulmonary disease (COPD) is still unclear. A meta-analysis of the original data sets of the randomised controlled trials published thus far was therefore performed. The main question was: "Are inhaled corticosteroids able to slow down the decline in lung function (FEV1) in COPD?" METHODS: A Medline search of papers published between 1983 and 1996 was performed and three studies were selected, two of which were published in full and one in abstract form. Patients with "asthmatic features" were excluded from the original data. Ninety five of the original 140 patients treated with inhaled corticosteroids (81 with 1500 micrograms beclomethasone daily, six with 1600 micrograms budesonide daily, and eight with 800 micrograms beclomethasone daily) and 88 patients treated with placebo (of the initial 144 patients) were included in the analysis. The effect on FEV1 was assessed by a multiple repeated measurement technique in which points of time in the study and treatment effects (inhaled corticosteroids compared with placebo) were investigated. RESULTS: No baseline differences were observed (mean age 61 years, mean FEV1 45% predicted). The estimated two year difference in prebronchodilator FEV1 was +0.034 l/year (95% confidence interval (CI) 0.005 to 0.063) in the inhaled corticosteroid group compared with placebo. The postbronchodilator FEV1 showed a difference of +0.039 l/year (95% CI -0.006 to 0.084). No beneficial effect was observed on the exacerbation rate. Worsening of the disease was the reason for drop out in four patients in the treatment group compared with nine in the placebo group. In the treatment group six of the 95 subjects dropped out because of an adverse effect which may have been related to the treatment compared with two of the 88 patients in the placebo group. CONCLUSIONS: This meta-analysis in patients with clearly defined moderately severe COPD showed a beneficial course of FEV1 during two years of treatment with relatively high daily dosages of inhaled corticosteroids.
In spontaneously breathing subjects, intrathoracic expiratory flow limitation can be detected by applying a negative expiratory pressure (NEP) at the mouth during tidal expiration. To assess whether NEP might increase upper airway resistance per se, the interrupter resistance of the respiratory system (Rint,rs) was computed with and without NEP by using the flow interruption technique in 12 awake healthy subjects, 6 nonsnorers (NS), and 6 nonapneic snorers (S). Expiratory flow (V) and Rint,rs were measured under control conditions with V increased voluntarily and during random application of brief (0.2-s) NEP pulses from -1 to -7 cmH(2)O, in both the seated and supine position. In NS, Rint,rs with spontaneous increase in V and with NEP was similar [3.10 +/- 0.19 and 3.30 +/- 0.18 cmH(2)O x l(-1) x s at spontaneous V of 1.0 +/- 0.01 l/s and at V of 1.1 +/- 0.07 l/s with NEP (-5 cmH(2)O), respectively]. In S, a marked increase in Rint,rs was found at all levels of NEP (P < 0.05). Rint,rs was 3.50 +/- 0.44 and 8.97 +/- 3.16 cmH(2)O x l(-1) x s at spontaneous V of 0.81 +/- 0.02 l/s and at V of 0.80 +/- 0.17 l/s with NEP (-5 cmH(2)O), respectively (P < 0.05). With NEP, Rint,rs was markedly higher in S than in NS both seated (F = 8.77; P < 0.01) and supine (F = 9.43; P < 0.01). In S, V increased much less with NEP than in NS and was sometimes lower than without NEP, especially in the supine position. This study indicates that during wakefulness nonapneic S have more collapsible upper airways than do NS, as reflected by the marked increase in Rint,rs with NEP. The latter leads occasionally to an actual decrease in V such as to invalidate the NEP method for detection of intrathoracic expiratory flow limitation.
The loss of upper airway (UA) dilators preactivation before inspiratory muscle contraction is an important determinant of the pathophysiology of obstructive sleep apnea. We hypothetized that phrenic nerve stimulation could provide a practical way to explore the effects of the dissociation between UA dilators and inspiratory muscles, and possibly to determine UA critical closing pressure during wakefulness. The pattern of inspiratory airflow was therefore studied in normal awake subjects during diaphragm twitches induced by either electrical phrenic stimulation (ES) or cervical magnetic stimulation (CMS) (n = 9) and with and without a nasal stent during ES (n = 7). End-expiratory stimulations applied during exclusive nasal breathing induced 200 to 300 ms twitch inspiratory flow. The average maximal twitch flow of flow-limited twitches was higher during CMS than ES (1.18 +/- 0.29 L.
Although persistent activation of the inspiratory muscles and narrowing of the glottic aperture during expiration have been indicated as relevant mechanisms leading to dynamic hyperinflation in acute asthma, expiratory flow limitation (EFL) has recently been proposed as a possible triggering factor for increasing endexpiratory lung volume (EELV). To establish whether the attainment of maximal flow rate during tidal expiration could elicit dynamic elevation of EELV, breathing pattern, change in EELV by measuring inspiratory capacity (IC) and occurrence of EFL by the negative expiratory pressure (NEP) method were monitored in 10 stable asthmatic subjects during methacholine-induced, progressive bronchoconstriction in seated position. Change in dyspnoea was scored using the Borg scale. At maximum response forced expiratory volume in one second (FEV1) fell on average by 45+/-2% (p<0.001 versus control), while IC decreased 29+/-2%, (by 0.89+/-0.07 L, (p<0.01 versus control)). Only 2 subjects exhibited EFL at the end of methacholine challenge. In 7 subjects EELV started to increase before the occurrence of EFL. Dyspnoea, which increased from 0.2+/-0.1 to 5.5+/-1.0 (Borg scale) at maximum response (p<0.001), was significantly related to the level of bronchoconstriction as assessed by change in (delta)FEV1 (r=0.72; p<0.001) and to dynamic hyperinflation as measured by deltaIC (r=0.50; p<0.001). However, for both deltaFEV1 and deltaIC the slope of the relationship with increasing dyspnoea was highly variable among the subjects. It is concluded that in acute methacholine-induced bronchoconstriction, dynamic hyperinflation may occur in the absence of expiratory flow limitation and that expiratory flow limitation does not represent the triggering factor to generate dynamic hyperinflation. In these circumstances, dyspnoea appears to be related to the increase in end-expiratory lung volume and not to the onset of expiratory flow limitation.
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Systemic capillary leak syndrome (SCLS) is a rare disorder of unknown etiology, characterized by recurrent hypovolemic shock attacks associated in most cases with a serum monoclonal immunoglobulin. Prophylactic therapy is usually disappointing and the outcome is often fatal. We report on a patient with recurrent hypovolemic shocks consistent with the diagnosis of SCLS associated with severe serum panhypogammaglobulinemia but no detectable monoclonal immunoglobulin or B cell proliferation. Attacks were often preceded by severe respiratory infections. Both infections and attacks were successfully prevented by i.v. gammaglobulin replacement. Further evaluation is needed to assess the efficacy of i.v. gammaglobulins in patients with SCLS but without hypogammaglobulinemia.
We prospectively studied features of pyogenic bacterial pneumonia in 263 consecutive human immunodeficiency virus-infected inpatients over a 6-month study period. Risk factors for bacterial pneumonia were examined by a case-control study that included 33 cases who presented with at least one episode of bacterial pneumonia and 80 controls without bacterial pneumonia. The estimated cumulative incidence of bacterial pneumonia per year was 12.5 cases per 100 inpatients (95% confidence interval [CI], 8.8-17.2). The 38 episodes of bacterial pneumonia that occurred in the 33 inpatients were mainly unilateral, but 32 episodes were patchy lobar or diffuse infiltrates. Microbiological etiologies were obtained in 33 of the 38 episodes of bacterial pneumonia. Thirty-seven pathogens were identified, including Streptococcus pneumoniae (16, of which 12 had a decreased susceptibility to penicillin), Haemophilus influenzae (6), and Pseudomonas aeruginosa (6). The risk factors for bacterial pneumonia that were identified after logistic regression included prior sinusitis within 1 month before admission (odds ratio [OR], 3.2; 95% CI, 1.1-9.1) and prior bacterial infection of the lower respiratory tract within 6 months before admission (OR, 3.1; 95% CI, 1.1-8.3).
The application of negative expiratory pressure (NEP) at end expiration has been shown to cause reflex-mediated activation of the genioglossus muscle in awake humans. To test whether a reflex contraction of pharyngeal dilator muscles also occurs in response to NEP applied in early expiration, the effect on genioglossus muscle reflex activity of NEP pulses of 500 ms, given 0.2 s after the onset of expiration and during the end-expiratory pause, was assessed in 10 normal awake subjects at rest. The raw and integrated surface electromyogram of the genioglossus (EMGgg) was recorded with airflow and mouth pressure under control conditions and with NEP ranging from -3 to -10 cmH2O. Intraoral EMGgg was also recorded under the same experimental conditions in two subjects. The application of NEP at the end-expiratory pause elicited a consistent reflex response of EMGgg in seven subjects with a mean latency of 68 +/- 5 ms. In contrast, when NEP was applied at the onset of expiration, EMGgg reflex activity was invariably observed in only one subject. No relationship was found between steady increase or abrupt fall in expiratory flow and the presence or the absence of a reflex activity of genioglossus during sudden application of NEP at the beginning of expiration. Our results show that a reflex activity of genioglossus is elicited much more commonly during application of NEP at the end rather than at the onset of expiration. These findings also suggest that when NEP is applied in early expiration to detect intrathoracic flow limitation the absence of upper airways narrowing does not imply the occurrence of a reflex-mediated activation of genioglossus and vice versa.
Inspiratory muscle fatigue can probably determine hypercapnic respiratory failure. Diaphragm fatigue is detected by electrical phrenic stimulation (ELS), but there is no simple tool to assess rib cage muscle (RCM) fatigue. Cervical magnetic stimulation (CMS) costimulates the phrenic nerves and RCM. We reasoned that changes in transdiaphragmatic pressure twitch (Pdi,tw) with CMS and ELS should be different after selective diaphragm vs. RCM fatigue. Five volunteers performed inspiratory resistive tasks while voluntarily uncoupling diaphragm and RCM. Baseline Pdi,twELS and Pdi,twCMS were 28.57 +/- 1.68 and 32.83 +/- 2.92 cmH2O. After selective diaphragm loading, Pdi,twELS and Pdi,twCMS were reduced by 39 and 26%, with comparable decreases in gastric pressure twitch (Pga,tw). Esophageal pressure twitch (Pes,tw) was better preserved with CMS. Therefore Pes,tw/Pga,tw was lower with ELS than CMS (-1.24 +/- 0.16 vs. -1.73 +/- 0.11, P = 0.05). After selective RCM loading, there was no diaphragm fatigue, but Pes,twCMS was significantly reduced (-30%). These findings support the role of rib cage stiffening by CMS-related RCM contraction in the ELS-CMS differences and suggest that CMS can be used to assess RCM fatigue.
Expiratory flow limitation (EFL), which promotes dynamic hyperinflation and increased work of breathing, often occurs in chronic obstructive pulmonary disease (COPD). The purpose of this study was to assess the effect of bronchodilators on EFL and end-expiratory lung volume in patients with moderate-to-severe COPD. EFL was assessed by applying negative expiratory pressure (NEP) at the mouth during tidal expiration. EFL was present when expiratory flow did not increase or increased only in the early phase of expiration with NEP. In 18 patients (age 65+/-2 yrs; forced expiratory volume in one second (FEV1)=45+/-4% predicted) pulmonary function tests and a series of NEP (-3.5 cmH2O) test breaths were performed at rest in a sitting position before and 20 min after inhalation of 400 microg of salbutamol. EFL was detected in 11 patients and persisted after salbutamol in all of these flow-limited (FL) patients. After bronchodilator administration FL patients exhibited a significant decrease in functional residual capacity (FRC) associated with an increase in inspiratory capacity (IC). In contrast, no changes in FRC and IC were observed in the seven non flow-limited (NFL) patients after administration of salbutamol. Except for one NFL patient, the other 17 patients (six NFL and 11 FL) had no reversibility of their bronchial obstruction (delta FEV1 <10% pred). In conclusion, patients with chronic obstructive pulmonary disease and expiratory flow limitation, even if nonresponders in terms of forced expiratory volume in one second, may benefit from bronchodilators because they can breathe, still in a flow-limited manner, at a lower lung volume.
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This study describes a non-invasive method for assessment of the lung transit time distribution of a tracer, using first-pass technetium-99m albumin angiocardiography and a model-free method of deconvolution. Ten patients received a first injection of 1 MBq kg-1 in the external jugular vein to position a gamma camera in the left anterior oblique position and two additional injections (5 MBq kg-1) to record first-pass angiocardiographic data. Right and left ventricular time-activity curves were derived from regions of interest every 0.5 s over a 1-min period. The left ventricular curve was deconvoluted by the right ventricular curve to obtain the lung transport function. The deconvolution procedure was based on a modified version of the Kalman filtering technique. The procedure was repeated at an interval of 30 min in eight patients. Two patients were re-examined up to 2 years later. Skewness, kurtosis and relative dispersion of the distributions did not change over time. We also found that the distribution, once normalized by its first moment, was independent of isolated changes in heart rate or cardiac output. Comparison of curve shapes at an interval of 30 min by point by point analysis demonstrated the reproducibility of the technique. We conclude that computation of the pulmonary transit time distribution of 99mTc-albumin from a standard angiocardiography procedure by model-free deconvolution is reliable and reproducible over time. We suggest that it may be a valuable tool for the non-invasive follow-up of the pulmonary circulation.
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A large number of drugs can induce pulmonary disease. We report the case of a female patient who was receiving cyproterone acetate for severe hirsutism. After 4 months of cyproterone therapy, she had dyspnea, pulmonary infiltrates, and a restrictive ventilatory defect. Bronchoalveolar lavage showed CD8+ lymphocytosis as well as increased neutrophils and eosinophils, a profile highly suggestive of an iatrogenic process. The patient showed no other significant clinical or biologic abnormality. Symptoms and functional abnormalities disappeared after withdrawal of cyproterone and reappeared after its reintroduction. This suggests that cyproterone acetate, a substance used to treat hirsutism and prostate cancer and in the composition of certain oral contraceptives, can be added to the list of drugs that may cause lymphocytic pneumonitis.