Recent epidemiological trends in extrapulmonary TB in Galicia, Spain.

OBJECTIVE: To describe the epidemiological trends and characteristics of extrapulmonary tuberculosis (EPTB) in Galicia, Spain, from 2000 to 2019.METHODS: This was a retrospective cohort study based on data from the Galician TB information system.RESULTS: Of the total number of TB cases (n = 15,871), 5,428 (34.2%) had EPTB. The absolute number of cases and incidence of EPTB decreased dramatically (from 480 cases and 17.8 cases/100,000 in 2000, to 172 and 6.4 cases/100,000 in 2019, respectively), with a mean annual decrease of respectively 64% and 4.7% for absolute cases and incidence rates. The risk for EPTB was higher in men than in women (RR 3.86, 95% CI 3.66-4.07). The most frequent age group was 15-44 years (2,234 patients, 41.2%); overall reductions per age group were 82% (0-14 years), 75% (15-44 years), 44% (45-64 years) and 63% (≥65 years), with statistically significant differences. The most frequently locations were the pleura (1,916 cases; 35.3%) and the lymph nodes (1,504; 27.7%).CONCLUSION: The incidence of EPTB in Galicia has decreased significantly in the last 20 years. The epidemiological characteristics have not changed, except for the number of patients with risk factors. This improvement of EPTB epidemiological trends coincides with the implementation of the programme for the prevention and control of TB, which suggests that it has been very effective in the control of the EPTB.

Nonlinear measure of synchrony between blood oxygen saturation and heart rate from nocturnal pulse oximetry in obstructive sleep apnoea syndrome.

This study focuses on analysis of the relationship between changes in blood oxygen saturation (SaO(2)) and heart rate (HR) recordings from nocturnal pulse oximetry (NPO) in patients suspected of suffering from obstructive sleep apnoea (OSA) syndrome. Two different analyses were developed: a classical frequency analysis based on the magnitude squared coherence (MSC) and a nonlinear analysis by means of a recently developed measure of synchrony, the cross-approximate entropy (cross-ApEn). A data set of 187 subjects was studied. We found significantly higher correlation and synchrony between oximetry signals from OSA positive patients compared with OSA negative subjects. We assessed the diagnostic ability to detect OSA syndrome of both the classical and nonlinear approaches by means of receiver operating characteristic (ROC) analyses with tenfold cross-validation. The nonlinear measure of synchrony significantly improved the results obtained with classical MSC: 69.2% sensitivity, 90.9% specificity and 78.1% accuracy were reached with MSC, whereas 83.7% sensitivity, 84.3% specificity and 84.0% accuracy were obtained with cross-ApEn. Our results suggest that the use of nonlinear measures of synchrony could provide essential information from oximetry signals, which cannot be obtained with classical spectral analysis.

Established immunity precludes adenovirus-mediated gene transfer in rat carotid arteries. Potential for immunosuppression and vector engineering to overcome barriers of immunity.

Preclinical arterial gene transfer studies with adenoviral vectors are typically performed in laboratory animals that lack immunity to adenovirus. However, human patients are likely to have prior exposures to adenovirus that might affect: (a) the success of arterial gene transfer; (b) the duration of recombinant gene expression; and (c) the likelihood of a destructive immune response to transduced cells. We confirmed a high prevalence (57%) in adult humans of neutralizing antibodies to adenovirus type 5. We then used a rat model to establish a central role for the immune system in determining the success as well as the duration of recombinant gene expression after adenovirus-mediated gene transfer into isolated arterial segments. Vector-mediated recombinant gene expression, which was successful in naive rats and prolonged by immunosuppression, was unsuccessful in the presence of established immunity to adenovirus. 4 d of immunosuppressive therapy permitted arterial gene transfer and expression in immune rats, but at decreased levels. Ultraviolet-irradiated adenoviral vectors, which mimic advanced-generation vectors (reduced viral gene expression and relatively preserved capsid function), were less immunogenic than were nonirradiated vectors. A primary exposure to ultraviolet-irradiated (but not nonirradiated) vectors permitted expression of a recombinant gene after redelivery of the same vector. In conclusion, arterial gene transfer with current type 5 adenoviral vectors is unlikely to result in significant levels of gene expression in the majority of humans. Both immunosuppression and further engineering of the vector genome to decrease expression of viral genes show promise in circumventing barriers to adenovirus-mediated arterial gene transfer.

Nonlinear characteristics of blood oxygen saturation from nocturnal oximetry for obstructive sleep apnoea detection.

Nocturnal oximetry is an attractive option for the diagnosis of obstructive sleep apnoea (OSA) syndrome because of its simplicity and low cost compared to polysomnography (PSG). The present study assesses nonlinear analysis of blood oxygen saturation (SaO(2)) from nocturnal oximetry as a diagnostic test to discriminate between OSA positive and OSA negative patients. A sample of 187 referred outpatients, clinically suspected of having OSA, was studied using nocturnal oximetry performed simultaneously with complete PSG. A positive OSA diagnosis was found for 111 cases, while the remaining 76 cases were classified as OSA negative. The following oximetric indices were obtained: cumulative time spent below a saturation of 90% (CT90), oxygen desaturation indices of 4% (ODI4), 3% (ODI3) and 2% (ODI2) and the delta index (Delta index). SaO(2) records were subsequently processed applying two nonlinear methods: central tendency measure (CTM) and Lempel-Ziv (LZ) complexity. Significant differences (p < 0.01) were found between OSA positive and OSA negative patients. Using CTM we obtained a sensitivity of 90.1% and a specificity of 82.9%, while with LZ the sensitivity was 86.5% and the specificity was 77.6%. CTM and LZ accuracies were higher than those provided by ODI4, ODI3, ODI2 and CT90. The results suggest that nonlinear analysis of SaO(2) signals from nocturnal oximetry could yield useful information in OSA diagnosis.

Coherence between oxygen saturation and heart rate obtained from pulse oximetric recordings in obstructive sleep apnoea.

In obstructive sleep apnoea (OSA) cyclical changes in oxygen saturation and heart rate in the period range of 30-120 s are observed. In these patients, we prospectively analyse the coherence of nocturnal SaO(2) and heart rate signals. A sample of 201 clinically suspected of having OSA were studied using nocturnal pulse oximetric and complete polysomnography. Coherence function versus period curves were categorized into three patterns: a positive pattern showing a predominant positive peak value of coherence in the period range of 30-120 s; a negative pattern if the predominant coherence was negative in the same range; and an undetermined pattern if no predominance was detected. One hundred and thirteen patients present a positive coherence pattern; 74.3% of these have OSA. A negative coherence pattern was observed for 28 patients; 85.7% of these have OSA. The remaining 60 patients present an undetermined pattern. Patients with OSA presented significantly higher maximal positive coherence and maximal negative coherence than those without OSA. We conclude that OSA patients present dynamic coordination and interdependence between SaO(2) and heart rate in specific frequencies.

Optimizing vascular gene transfer of plasminogen activator inhibitor 1.

The vessel wall fibrinolytic system plays an important role in maintaining the arterial phenotype and in regulating the arterial response to injury. Plasminogen activator inhibitor type 1 (PAI-1) regulates tissue fibrinolysis and is expressed in arterial tissue; however, its biological role remains uncertain. To help elucidate the role of PAI-1 in the artery wall, and to begin to clarify whether manipulation of vascular PAI-1 expression might be a target for gene therapy, we used adenoviral vectors to increase expression of rat PAI-1 in rat carotid arteries. Infusion of an adenoviral vector in which PAI-1 expression was driven by a promoter derived from the Rous sarcoma virus (RSV) did not increase PAI-1 expression above endogenous levels. To improve PAI-1 expression, we modified the vector by (1) truncating the 3' untranslated region of PAI-1 to increase the mRNA half-life, (2) substituting the SRalpha or the cytomegalovirus (CMV) promoter for the RSV promoter, (3) including an intron in the expression cassette, and (4) altering the direction of transcription of the transgene cassette. The optimal expression vector, revealed by in vitro studies, contained the CMV promoter, an intron, and a truncated PAI-1 mRNA. This vector increased PAI-1 expression by 30-fold over control levels in vitro and by 1.6 to 2-fold over endogenous levels in vivo. This vector will be useful for elucidating the role of PAI-1 in arterial pathobiology. Because genes that are important in maintaining the vascular phenotype are likely to be expressed in the vasculature, the technical issues of how to increase in vivo expression of endogenous genes are highly relevant to the development of genetic therapies for vascular disease.

Monoclonal antibodies specific for a conformationally altered state of fibrinogen.

Four monoclonal antibodies were selected by their ability to discriminate surface-bound from soluble fibrinogen. These antibodies reacted with insolubilized fibrinogen but not other immobilized proteins and their reaction with surface-bound fibrinogen was not diminished by a 100-fold excess of soluble fibrinogen. The antibodies reacted with the same or spatially proximal epitopes, and the recognized epitope(s) resided within the gamma chain segment of the D domain of fibrinogen. Fab fragments of the antibodies inhibited fibrin polymerization in a dose dependent manner, suggesting that the epitope(s) was also exposed by the conversion of fibrinogen to fibrin. These data indicate that adsorption of fibrinogen onto a surface induces conformational changes and that similar changes are also evoked when fibrinogen is converted into fibrin.

Biological and thrombolytic properties of proenzyme and active forms of human urokinase--I. Fibrinolytic and fibrinogenolytic properties in human plasma in vitro of urokinases obtained from human urine or by recombinant DNA technology.

The fibrinolytic and fibrinogenolytic properties of recombinant pro-urokinase (Rec-pro-UK) and recombinant urokinase (Rec-UK) obtained by expression of the human urokinase cDNA in E. coli, were compared with those of natural urokinase (Nat-UK) of urinary origin and of tissue-type plasminogen activator (t-PA) in a system, composed of a radioactive human plasma clot immersed in citrated human plasma. The specific fibrinolytic effects of Nat-UK, Rec-pro-UK and Rec-UK were very similar, causing significant clot lysis at concentrations of 100 IU/ml plasma or more. t-PA caused equivalent degrees of clot lysis at 10-fold lower concentrations. Activation of the fibrinolytic system in the plasma (fibrinogenolysis), was not observed with t-PA in concentrations which induced complete clot lysis within 5 hr (20-30 IU/ml plasma). With Nat-UK and Rec-UK, all concentrations which caused significant clot lysis (100-200 IU/ml plasma) also caused extensive activation of the plasma fibrinolytic system. With Rec-pro-UK an intermediate response was obtained. The highest amounts required for complete clot lysis in 5 hr (200 IU/ml plasma) also caused significant fibrinogenolysis. At intermediate concentrations (50-100 IU/ml), however, significant clot lysis (40-80%) was observed without systemic fibrinolytic activation.

Influence of exogenous and endogenous tissue-type plasminogen activator on the lysability of clots in a plasma milieu in vitro.

The fibrinolytic potential of tissue-type plasminogen activator (t-PA) either incorporated in a clot (endogenous) or added to the surrounding plasma (exogenous), was studied in an in vitro system consisting of 125I-labeled human plasma clots (200 microliters) immersed in human plasma (2 ml). Clot lysis was measured as a function of endogenous t-PA concentration (in the absence of added exogenous t-PA), as a function of exogenous t-PA concentration (without added endogenous t-PA) and as a function of the same concentration of both endogenous and exogenous t-PA. Equivalent clot lysis was obtained with a 2 to 4 times lower concentration of endogenous t-PA as compared to exogenous t-PA, corresponding to a 20 to 40 times smaller total amount of endogenous versus exogenous t-PA. Fifty percent lysis in 5 hrs was obtained with about 5 IU/ml of endogenous t-PA or with 10 IU/ml of exogenous t-PA. The presence of both exogenous (10 IU/ml) and endogenous (5 IU/ml) t-PA resulted in 50 percent lysis in 1.5 hrs, indicating that t-PA incorporated in a thrombus contributes significantly to its lysis by exogenous t-PA. Similar results were obtained with plasma obtained after 10 min of venous occlusion in seven healthy subjects. Spontaneous clot lysis within 5 hrs was only observed with post-occlusion clots in pre- or post- occlusion plasma in two subjects in whom the t-PA level rose to 10-15 IU t-PA/ml. In the five other subjects with post-occlusion t-PA levels below 2 IU/ml, no clot lysis was observed within 24 hrs. The influence of the fast-acting inhibitor of t-PA on clot lysability by endogenous or exogenous t-PA was investigated by immersing clots prepared from normal or inhibitor-rich plasma (endogenous inhibitor) in normal or inhibitor-rich plasma (exogenous inhibitor). Exogenous t-PA inhibitor efficiently neutralizes clot lysis by both exogenous and endogenous t-PA. Endogenous t-PA inhibitor, however, efficiently neutralizes endogenous t-PA but has little influence on clot lysis by exogenous t-PA. These findings indicate that t-PA inhibitor is not concentrated into a clot and that t-PA inhibitor in plasma efficiently neutralizes t-PA incorporated in a clot. alpha 2-Antiplasmin depleted plasma clots were more susceptible to lysis by both endogenous and exogenous t-PA than normal clots.(ABSTRACT TRUNCATED AT 400 WORDS)

Snoring and myocardial infarction: a 4-year follow-up study.

The association between snoring and myocardial infarction was studied in 1453 people of both sexes aged 20-70 years. The study was carried out in a population of 92,364 residents and the subjects were recruited using the Electoral Census. A questionnaire was sent to all participants, asking about snoring and cardiovascular risk factors. Hospital records were checked for the next 4 years to establish how many of them developed myocardial infarction. At the beginning of the follow-up study 39 patients were diagnosed with ischaemic heart disease. Of the other 1414 participants, 571 (40.4%) were snorers and 843 (59.6%) non-snorers. Twenty-one developed myocardial infarction in the snorer group and four in the non-snorer group. The snorer group presents an adjusted relative risk of myocardial infarction of 3.08 (95% CI 1.01-9.46) with respect to non-snorers. We conclude that snoring seems to be a potential risk factor for myocardial infarction.

Airway disorders and pulmonary function in snorers. A population-based study.

The aim of our study was to determine the relationship between snoring, airway disorders and pulmonary function in the general population. We performed a stratified random sampling from the population (n = 92,364). Four hundred subjects agreed to participate and were invited to the clinic, where a detailed medical history, physical examination, spirometric test and maximal respiratory pressures measurements were carried out. Snoring was reported by 152 subjects (38%). Nasal obstruction and the presence of abnormal pharynx exploration were more frequent in subjects with snoring. Age, body mass index and neck circumference were significantly higher in the snorer group. In addition, we found that the non-snoring group had a significantly higher frequency of tonsillectomy during infancy and adolescence than the snorer group. We did not detect any significant difference in spirometric test values or in maximal respiratory pressure values between snorer group and non-snorer group. In conclusion, in the general population snoring is associated with nasal obstruction and abnormal pharynx exploration. Furthermore, snoring appears not to be associated with modifications in spirometric or in maximal respiratory pressure tests.

Health-related quality of life in patients with obstructive sleep apnea: effects of long-term positive airway pressure treatment.

The aim of the present study was to determine the effect of middle and long-term positive airway pressure (CPAP) treatment on the health-related quality of life in patients with obstructive sleep apnea. We prospectively studied two groups of patients with this disease; a group of 42 patients (33 men and 9 women) with a mean age of 55.2 +/- 7.4 years and a body mass index of 33.5 +/- 6.4 kg/m2 treated with CPAP for 6-months, and another group of 42 patients (34 men and 8 women) with a mean age of 54.4 +/- 10.5 years and a body mass index of 33.2 +/- 4.0 kg/m2 treated with CPAP for 18-months. The health related quality of life was assessed by administering a Medical Outcomes Study Short Form-36 (SF-36) questionnaire before and after CPAP therapy. Patients treated with CPAP for 6 months only improved significantly in the vitality dimension and this change was clinically relevant (standard error of the measurement = 1.43 SEmeas). In contrast, those treated with CPAP for a long period (18-month) showed statistically significant improvement at post-treatment in five SF-36 dimensions: physical functioning (P < 0.001), role physical (P < 0.01), social functioning (P < 0.01), vitality (P < 0.001), and general health perception (P < 0.001). In four of these dimensions the improvement was clinically relevant: role physical (1.16 SEmeas), social functioning (1.35 SEmeas), vitality (1.35 SEmeas), and general health perception (2.05 SEmeas). Using two different global rating of change (independent measures or anchors), the minimal change important difference for patients treated with CPAP for 6 months ranged from 20.7 to 24.2 points on the vitality dimension; and for patients with CPAP for 18-months it ranged from 2.5 to 7.5 points on the physical role, 5.5-6.6 points on social functioning, 7.5-8.7 on vitality, and 13.5-15.5 on general health perception dimension. We conclude that health-related quality of life of obstructive sleep apnea patients improves with long term CPAP treatment and these changes are clinically relevant in several health dimensions.

Screening of obstructive sleep apnoea: heart rate spectral analysis of nocturnal pulse oximetric recording.

Using heart rate spectral analysis of nocturnal pulse oximetry, we prospectively evaluated the utility of this methodology in patients clinically suspected of having obstructive sleep apnoea (OSA). A hundred and ninety-seven outpatients referred with symptoms compatible with the diagnosis of OSA were studied. All participants had nocturnal pulse oximetry performed simultaneously with conventional polysomnography. Power density of heart rate obtained by nocturnal pulse oximetry was analysed using fast Fourier transformation of a Hamming-windowed signal. Recording test results were classified as abnormal (suspicion of OSA) in the presence of a peak in the periodogram between period boundaries 30-70 sec. A normal test result was defined as the absence of the 30-70 sec peak in the periodogram. The total area of the periodogram (S(TOT)), the area enclosed in the periodogram between the period boundaries 30-70 sec (S(30-70)), the area enclosed in the period boundaries 30-70 sec with respect to the total area of the periodogram (S) and the peak amplitude 30-70 sec (PA) were measured. The presence of a peak in the periodogram has a sensitivity of 81.3%, a specificity of 91.5% a positive predictive value of 89.1% and a negative predictive value of 85.1% for OSA diagnosis. The OSA patients were found to have higher values of S(TOT), S(30-70), S and PA than the non OSA patients. Receiver operating characteristics (ROC) curve was constructed at different thresholds of S(TOT), S(30-70) S and PA. For a PA threshold of 10(%)2, heart rate spectra analysis sensitivity for OSA was 58% and specificity was 92%. Furthermore, the positive and negative predictive values for diagnosis of OSA were 87 and 72% respectively. Apnoea hypopnea index (AHI) correlated significantly with S(TOT) (r=0.44; P<0.001), S(30-70) (r=0.59: P<0.001), S (r=0.58; P<0.001) and PA (r=0.58; P<0.001). According to our results, heart rate spectral analys s obtained by nocturnal pulse oximetry and identification of peak in the periodogram between period boundaries 30-70 sec could be useful as a diagnostic technique for OSA patients.

[Symptoms of sleep apnea syndrome in the general population]. / Sintomatología del síndrome de apnea del sueño en la población general.

The aim of this study was to determine the clinical features of patients with sleep apnea syndrome (SAS) in the general population. One hundred ten individuals were selected randomly from the census and given hospital appointments. Case histories were taken and complete physical examinations were made. Nighttime respiratory polysomnograms were performed. Twenty-two (20%) of the 110 subjects presented SAS. In the SAS group, 59.1% were habitual snorers and 22.7% reported daytime hypersomnolence. The SAS patients has a mean age of 59.6 +/- 8.8 years and 45.4% showed alterations of the pharynx. No differences in spirometric variables were observed. Only age and daytime hypersomnolence predicted SAS in the multivariate analysis. We conclude that the prevalence of snoring, daytime hypersomnolence, pharyngeal alterations are higher in patients with SAS. The patients are also older. Only age and daytime hypersomnolence predicted of SAS.

[A population study of the efficacy of pulsioxymetry in diagnosing obstructive sleep apnoea syndrome]. / Eficacia de la pulsioximetría en el diagnóstico del síndrome de apnea obstructiva durante el sueño en un estudio poblacional.

OBJECTIVES: To evaluate the use at home of night-time pulsioxymetry to diagnose obstructive sleep apnoea syndrome in the general population. DESIGN: Cros-sectional study of diagnostic tests. PARTICIPANTS: Random sample of 70 individuals chosen from a Health Centre´s appointment records. MAIN MEASUREMENTS: Anamnesis concerning sleep and respiratory disorders during sleep, anthropometric measurements, Epworth´s sleepiness scale, home night-time pulsioxymetry and polysomnography. RESULTS: Visual inspection by oxymetry gave 82% sensitivity (95% CI, 62-93) and 69% specificity (95% CI, 53-82) for the diagnosis of obstructive sleep apnoea syndrome. Other indices such as the time with oxygen saturation below 90% and the number of desaturations above 4% gave a sensitivity of 82% and 86% and specificity of 63% and 65%, respectively. All the cases of clinically significant obstructive apnoea were diagnosed by pulsioxymetry. CONCLUSIONS: Night-time pulsioxymetry is a useful test for general screening of obstructive sleep apnoea.

[Snoring and vascular diseases]. / El ronquido y las enfermedades vasculares.

The aim of this study is to review the evidence linking snoring with vascular disease. This has been a topic of numerous investigations with divergent results, mainly because of the differences in methodology employed in various studies, such as inclusion of confounding factors, methods of measures, etc. While some studies shows that snoring is a risk factor for vascular disease, another reached the opposite conclusion. Consequently, based on the available information, it s very difficult to conclude that snoring is an independent risk factor for vascular complications as hypertension and cardiovascular and cerebrovascular disease.

[Pulmonary diffusion of carbon monoxide in 2 clinical situations: bronchial asthma and diabetes mellitus]. / Estudio de la difusión pulmonar de monóxido de carbono en dos situaciones clínicas: asma bronquial y diabetes mellitus.

OBJECTIVE: The aim of our work has been the study and comparison of diffusion capacity of CO (DLCO) in two different clinical situations: bronchial asthma and diabetes mellitus. METHOD: We have studied 16 control subjects, 38 patients with bronchial asthma and 65 patients with diabetes mellitus. We performed CO pulmonary diffusion tests by single breath method to determine two components: membrane diffusion factor (Dm) and pulmonary capillary blood volume (Vc). RESULTS: We have found a positive correlation of FEV1 with Dm. The bronchial asthma group had a lower FEV1 and FEF25-75% and an increase in DLCO, Dm and Vc, with respect to the control group. The diabetes mellitus group presented a decrease in CVF, FEV1, DLCO and Vc, with respect to the control group. The bronchial asthma group showed a lower ratio of Dm/Vc than the control and diabetes groups. CONCLUSIONS: The bronchial asthma patients have an increase in CO pulmonary diffusion, membrane diffusion factor and pulmonary capillary volume. However, the diabetes mellitus patients present a decrease in CO pulmonary diffusion mainly due to pulmonary capillary volume.

[Study of adrenal function in patients with active pulmonary tuberculosis]. / Estudio de la función adrenal en pacientes con tuberculosis pulmonar activa.

In order to assess the impact of tuberculosis on the adrenal glands, 13 patients diagnosed of active pulmonary tuberculosis are studied. To this effect, basal cortisol concentrations and after stimulation with Synacthen and Nuvacthen depot were determined. In our patients, adrenal function remained intact, having as well no deleterious effect on it the treatment with tuberculostatics.

[The clinical characteristics of pulmonary tuberculosis in the elderly]. / Características clínicas de la tuberculosis pulmonar en el anciano.

Pulmonary tuberculosis remains as a significant clinical problem in the elderly. To describe age-related differences in disease manifestations, a comparison was made taking in consideration predisposing factors, clinical features, radiographic findings and diagnostic approaches in cases of pulmonary tuberculosis between two groups: equal o higher of 60 years and lower of 60 years. Elderly patients had a higher number of antecedents of previous tuberculosis and underlying diseases than younger patients. At admission, symptoms like fever and hemoptysis were more frequent in the younger group. Radiographic findings revealed that upper lung infiltrates were still common in both groups, and that elderly patients presented less pleural effusions and cavitary lesions than younger patients. Since there were differences in the clinical presentations of pulmonary tuberculosis in the elderly group, a high index of suspicion for the disease should be maintained.