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.

The classification of oximetry signals using Bayesian neural networks to assist in the detection of obstructive sleep apnoea syndrome.

In the present study, multilayer perceptron (MLP) neural networks were applied to help in the diagnosis of obstructive sleep apnoea syndrome (OSAS). Oxygen saturation (SaO(2)) recordings from nocturnal pulse oximetry were used for this purpose. We performed time and spectral analysis of these signals to extract 14 features related to OSAS. The performance of two different MLP classifiers was compared: maximum likelihood (ML) and Bayesian (BY) MLP networks. A total of 187 subjects suspected of suffering from OSAS took part in the study. Their SaO(2) signals were divided into a training set with 74 recordings and a test set with 113 recordings. BY-MLP networks achieved the best performance on the test set with 85.58% accuracy (87.76% sensitivity and 82.39% specificity). These results were substantially better than those provided by ML-MLP networks, which were affected by overfitting and achieved an accuracy of 76.81% (86.42% sensitivity and 62.83% specificity). Our results suggest that the Bayesian framework is preferred to implement our MLP classifiers. The proposed BY-MLP networks could be used for early OSAS detection. They could contribute to overcome the difficulties of nocturnal polysomnography (PSG) and thus reduce the demand for these studies.

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.

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.

Heart rate regularity analysis obtained from pulse oximetric recordings in the diagnosis of obstructive sleep apnea.

Approximate entropy (ApEn) is a technique that can be used to quantify the irregularity or variability of time series. We prospectively evaluated the validity of ApEn of heart rate data obtained from pulse oximetric recordings as a diagnostic test for obstructive sleep apnea (OSA) in patients clinically suspected of suffering this disease. A sample of 187 referred outpatients (147 men and 40 women), with a mean age of 57.9+/-12.8 years and a body mass index of 29.5+/-5.5 kg/m(2), clinically suspected of having OSA were studied using nocturnal pulse oximetric recording performed simultaneously with complete polysomnography. A diagnosis of OSA was confirmed in 111 (59.3%). Patients with OSA presented significantly higher ApEn levels than those without OSA (1.334+/-0.189 vs 1.167+/-0.182). Chronic obstructive pulmonary disease (COPD) was diagnosed for 42 patients. Among these patients, 22 (52.4%) were diagnosed with OSA. COPD patients with OSA showed significantly higher ApEn levels than COPD patients without OSA (1.337+/-0.193 vs 1.184+/-0.173; p=0.01). ApEn correlated significantly with apnea-hypopnea index (r=0.38; p=0.000). There was no significant correlation between ApEn and either age or body mass index. No significant changes were observed in ApEn throughout the night in OSA patients. Using receiver operating characteristic curve analysis, we obtained a diagnostic sensitivity of 71.2%, specificity of 78.9%, positive predictive value of 81.3%, and negative predictive value of 66% at a threshold of 1.272. We conclude that ApEn analysis of heart rate data obtained from pulse oximetric recordings could be a useful tool in the study of OSA.

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.

Prospective evaluation of an oral appliance in the treatment of obstructive sleep apnea syndrome.

The purpose of this study was to investigate the effects of an oral appliance (OA), with and without mandible advance, in the treatment of obstructive sleep apnea syndrome (OSA). Twenty-four patients diagnosed with OSA agreed to participate in this study. The patients were treated for 3 months (with a removable soft elastic silicone positioner customized with thermoplastic silicone and with a 5-mm opening). Patients were selected, using a randomized design, to receive an OA model either with (12 patients) or without advance (12 patients). Before treatment, a snoring questionnaire, the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36), the Functional Outcomes of Sleep Questionnaire (FOSQ), the Epworth Sleepiness Scale (ESS), and polysomnography were completed. Fifteen subjects completed the protocol (13 men, two women). With respect to basal values, the mandible-advanced OA group presented a decrease in the mean apnea-hypopnea index (AHI) (33.8+/-4.7 versus 9.6+/-2.1; p<0.01), number of arousals per hour (33.8+/-13.9 versus 16.0+/-1.5; p<0.05), ESS score (14.7+/-5.1 versus 5.1+/-1.9; p<0.05), snoring score (15.4+/-1.9 versus 10.1+/-3.2; p<0.05), and total FOSQ score (78.1+/-22.6 versus 99.3+/-14.4; p<0.05). After treatment, the non-advanced group presented a decrease in the mean AHI (24.0+/-12.2 versus. 11.7+/-7.9; p<0.05). However, no significant differences were found in the number of arousals per hour, ESS score, snoring, and total FOSQ score in the non-advanced group. Neither study group showed significant difference in mean SF36 scores. Oral appliances, especially those that advance the mandible, offer an effective treatment for OSA.

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.

Effect of the first infliximab infusion on sleep and alertness in patients with active rheumatoid arthritis.

OBJECTIVE: To assess the benefit of the first infliximab infusion on sleep disturbances in patients with RA Material and methods: Evaluation of RA activity, sleepiness (Epworth scale and multiple sleep latency test), alertness (steer clear test), and sleep structure (polysomnography) were conducted before and after the first infusion of infliximab in six female patients with RA. RESULTS: The day after the first infliximab infusion, the mean (SD) number of tender (20 (2.4)) or swollen (15.3 (2)) joints and the morning stiffness (140 (61.9) min) had not changed. There were significant improvements in the median number of total sleep stage transitions per hour (median (IR) before v after infusion: 20.5 (43) v 7.5 (6); Wilcoxon paired test, p = 0.014), median percentage of phase I+II (83.5 (8) v 54.5 (24); p = 0.023), percentage of REM stages (2 (10) v 11.5 (8); p = 0.014), median percentage sleep efficiency (44 (22) v 75 (18); p = 0.014), median sleep latency (77.5 (150) v 25.5 (23) min; p = 0.023), and median number of hits in the steer clear test (48.5 (86) v 6 (45); p = 0.023). Neither objective nor subjective daytime sleepiness was noted. One obese patient had obstructive sleep apnoea syndrome. CONCLUSIONS: Sleep and the alertness disturbances in RA improve with infliximab treatment. Improvement appears unrelated to joint discomfort amelioration but suggests a central effect through inhibition of circulating TNFalpha levels.

[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.

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.

[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.

[Epidemiologic study on tuberculosis in the health area of Santiago de Compostela in 1995, 1996, 1997, and 1998]. / Estudio epidemiológico de la tuberculosis en el Area Sanitaria de Santiago de Compostela durante los años 1995, 1996, 1997 y 1998.

BACKGROUND: We report the epidemiological characteristics of tuberculosis(TB) in the area of Santiago de Compostela (Spain) between 1995 and 1998. METHODS: Inclusion criteria were: 1) microbiological and/or pathological diagnosis of TB in any specimen, and 2) consistent recent medical history of TB with reading > 5 mm to 2 TU PPD tuberculin test 48-72 hours after injection, and adenosine deaminase in pleural effusion > 47 IU/ml. RESULTS: 1,150 patients were included (685 males and 465 females), with mean of age (X) 38.9 years (19.8 SD), range 3 months-88 years. The number of cases was 307 during 1995 and 1996, 302 in 1997 and 213 in 1998. The incidence rate (per 100,000 habitants) was 78.3 in 1995 and 1996, 79.8 in 1997 and 61.9 in 1998. The incidence rate of meningitis was 1.8 in 1995, 1.3 in 1996, 1.05 in 1997 and 0.8 in 1998, with no meningitis in children under 5 years. Cases in association with VIH were 4.2% in 1995, 3.3 in 1996, 5.4 in 1997 and 3.2 in 1998. More of the 50% of cases in both genders were between 15 and 40 years old with another peak over 65 years. The ratio men/woman was 1.8 in 1995 and 1.4 in 1996, 1997 and 1998. CONCLUSIONS: The incidence of tuberculosis has diminished during the last year, but is too early to know the real tendency.

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.

Oximetry spectral analysis in the diagnosis of obstructive sleep apnoea.

Using spectral analysis of oximetry data, we prospectively evaluated the validity of this methodology in patients clinically suspected of suffering from obstructive sleep apnoea (OSA). A total of 233 outpatients were studied. Nocturnal oximetry was performed simultaneously with conventional polysomnography for all participants. The power density of oxygen saturation was analysed using Fast-Fourier transformation of the oximetric signal. Nocturnal oximetry test results were considered as abnormal (suspicion of OSA) if a peak in the spectrum between the period boundaries 30 and 70 s was observed. A normal test result was defined as the absence of the 30-70 s peak from the spectrum. Single-blind evaluation was performed by three independent observers, and agreement of two or more of these was considered definitive. The peak amplitude and the ratio of the area enclosed in the 30-70 s peak to the total area of the spectrum (r(S)) were measured. The presence of a peak has a sensitivity of 78%, a specificity of 89%, a positive predictive value of 89% and a negative predictive value of 78%. Apnoea-hypopnoea indexes were correlated significantly with peak amplitude (r=0.74; P<0.001) and with r(S) (r=0.69; P<0.001). For a peak amplitude threshold of 0.7%(2), the sensitivity was 94% and the specificity was 65% for OSA diagnosis. Using a threshold for r(S) of 0.15, the sensitivity was 91% and the specificity was 67%. Thus the spectral analysis of nocturnal oximetry and identification of a peak at 30-70 s could be useful as a diagnostic technique for OSA subjects.

Prevalence of sleep disordered breathing and sleep apnea in 50- to 70-year-old individuals. A survey.

PURPOSE: To determine the prevalence of sleep disordered breathing (SDB) and sleep apnea syndrome (SAS) in a general population aged from 50 to 70 years. SUBJECTS AND METHODS: We recruited 76 individuals aged between 50 and 70 years, chosen at random from the electoral census. They were invited to the clinic where a detailed medical history was taken and physical examination, ENT examination, pulmonary function tests and night time recording of respiratory variables performed. RESULTS: The prevalence of SDB (apnea-hypopnea index >/= 5) was 28.9%, and there were no differences between men (28%) and women (30%). However, the prevalence of SAS was 6.8%, and there were differences between men (5 cases) and women (0 cases) (p = 0.0521). Subjects in the SDB group had higher systolic blood pressure than in the non-SDB group (p < 0.05). CONCLUSIONS: SDB and SAS are common among 50- to 70-year olds. The prevalence of SDB was 28.9% and the prevalence of SAS was 6.8%.

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.

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.