Respiratory symptoms and chronic bronchitis in people with and without HIV infection.

OBJECTIVES: High rates of respiratory symptoms and chronic bronchitis (CB) are reported in people with HIV infection (PWH). We investigated the prevalence of respiratory symptoms and CB in PWH and HIV-negative people in the Pharmacokinetic and clinical Observations in PeoPle over fiftY (POPPY) study. METHODS: Assessment of respiratory symptoms and CB was undertaken using the modified form of the St. George's Respiratory Questionnaire for chronic obstructive pulmonary disease (COPD). Univariate (χ2 tests, Mann-Whitney U tests and Spearman's rank correlation) and multivariable (linear and logistic regression) analyses were performed to consider associations of respiratory symptoms with demographic, lifestyle and HIV-related parameters, and with depressive symptoms and quality of life. RESULTS: Among the 619 participants, respiratory Symptom scores were higher in older and younger PWH compared to older HIV-negative people, with median (interquartile range) scores of 17.7 (6.2, 39.5), 17.5 (0.9, 30.0) and 9.0 (0.9, 17.5), respectively (P = 0.0001); these differences remained significant after confounder adjustment. Sixty-three participants (10.2%) met the criteria for CB [44 (14.0%) older PWH, 14 (9.2%) younger PWH, and five (3.3%) older HIV-negative people; P = 0.002], with these differences also remaining after adjustment for confounding variables, particularly smoking status [older vs. younger PWH: odds ratio (OR) 4.48 (95% confidence interval (CI) 1.64, 12.30); P = 0.004; older PWH vs. HIV-negative people: OR 4.53 (95% CI 1.12, 18.28); P = 0.03]. Respiratory symptoms and CB were both associated with greater depressive symptom scores and poorer quality of life. No strong associations were reported between CB and immune function, HIV RNA or previous diagnosis of any AIDS event. CONCLUSIONS: Respiratory symptoms and CB are more common in PWH than in demographically and lifestyle-similar HIV-negative people and are associated with poorer mental health and quality of life.

Investigation of the safety and feasibility of AAV1/SERCA2a gene transfer in patients with chronic heart failure supported with a left ventricular assist device - the SERCA-LVAD TRIAL.

The SERCA-LVAD trial was a phase 2a trial assessing the safety and feasibility of delivering an adeno-associated vector 1 carrying the cardiac isoform of the sarcoplasmic reticulum calcium ATPase (AAV1/SERCA2a) to adult chronic heart failure patients implanted with a left ventricular assist device. The SERCA-LVAD trial was one of a program of AAV1/SERCA2a cardiac gene therapy trials including CUPID1, CUPID 2 and AGENT trials. Enroled subjects were randomised to receive a single intracoronary infusion of 1 × 1013 DNase-resistant AAV1/SERCA2a particles or a placebo solution in a double-blinded design, stratified by presence of neutralising antibodies to AAV. Elective endomyocardial biopsy was performed at 6 months unless the subject had undergone cardiac transplantation, with myocardial samples assessed for the presence of exogenous viral DNA from the treatment vector. Safety assessments including ELISPOT were serially performed. Although designed as a 24 subject trial, recruitment was stopped after five subjects had been randomised and received infusion due to the neutral result from the CUPID 2 trial. Here we describe the results from the 5 patients at 3 years follow up, which confirmed that viral DNA was delivered to the failing human heart in 2 patients receiving gene therapy with vector detectable at follow up endomyocardial biopsy or cardiac transplantation. Absolute levels of detectable transgene DNA were low, and no functional benefit was observed. There were no safety concerns in this small cohort. This trial identified some of the challenges of performing gene therapy trials in this LVAD patient cohort which may help guide future trial design.

Factors associated with obesity in the Pharmacokinetic and Clinical Observations in People over Fifty (POPPY) cohort: an observational cross-sectional analysis.

OBJECTIVES: The aims of the study were to describe the prevalence of obesity in the Pharmacokinetic and Clinical Observations in People over Fifty (POPPY) cohort, to identify demographic, clinical and HIV-specific factors associated with obesity, and to characterize the association between obesity and sociodemographic, clinical and HIV-specific factors and quality of life (QoL). METHODS: A cross-sectional analysis was carried out of baseline data from the three groups ["older" people with HIV infection (PWH) aged ≥ 50 years, "younger" PWH aged < 50 years and HIV-negative controls aged ≥ 50 years] within the POPPY cohort. Obesity was defined as a body mass index (BMI) > 30 kg/m2 . RESULTS: A total of 1361 subjects were included in the study, of whom 335 (24.6%) were obese. The prevalence of obesity was higher in controls (22.3%) than in older (16.8%) and younger (14.2%) PWH, with no differences between the two groups of PWH. Factors associated with obesity were older age, female gender, black African ethnicity and alcohol consumption. Recreational drug use and a higher current CD4 T-cell count (in PWH) were associated with lower and higher odds of being obese, respectively. The presence of obesity was associated with worse physical health QoL scores, higher odds of having cardiovascular disease, type 2 diabetes and hypertension, but lower odds of having osteopenia/osteoporosis, irrespective of HIV status. CONCLUSIONS: Despite a lower prevalence of obesity in PWH, specific subgroups (women, people of black African origin and older people) were more likely to be obese, and negative health consequences of obesity were evident, regardless of HIV status. Whether targeted preventive strategies can reduce the burden of obesity and its complications in PWH remains to be determined.

Level of agreement between frequently used cardiovascular risk calculators in people living with HIV.

OBJECTIVES: The aim of the study was to describe agreement between the QRISK2, Framingham and Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) cardiovascular disease (CVD) risk calculators in a large UK study of people living with HIV (PLWH). METHODS: PLWH enrolled in the Pharmacokinetic and Clinical Observations in People over Fifty (POPPY) study without a prior CVD event were included in this study. QRISK2, Framingham CVD and the full and reduced D:A:D CVD scores were calculated; participants were stratified into 'low' (< 10%), 'intermediate' (10-20%) and 'high' (> 20%) categories for each. Agreement between scores was assessed using weighted kappas and Bland-Altman plots. RESULTS: The 730 included participants were predominantly male (636; 87.1%) and of white ethnicity (645; 88.5%), with a median age of 53 [interquartile range (IQR) 49-59] years. The median calculated 10-year CVD risk was 11.9% (IQR 6.8-18.4%), 8.9% (IQR 4.6-15.0%), 8.5% (IQR 4.8-14.6%) and 6.9% (IQR 4.1-11.1%) when using the Framingham, QRISK2, and full and reduced D:A:D scores, respectively. Agreement between the different scores was generally moderate, with the highest level of agreement being between the Framingham and QRISK2 scores (weighted kappa = 0.65) but with most other kappa coefficients in the 0.50-0.60 range. CONCLUSIONS: Estimates of predicted 10-year CVD risk obtained with commonly used CVD risk prediction tools demonstrate, in general, only moderate agreement among PLWH in the UK. While further validation with clinical endpoints is required, our findings suggest that care should be taken when interpreting any score alone.

Multiparametric modeling of the ineffective efforts in assisted ventilation within an ICU.

In the context of assisted ventilation in ICU, it is of vital importance to keep a high synchronization between the patient's attempt to breath and the assisted ventilation event, so that the patient receives the ventilation support requested. In this work, experimental equipment is employed, which allows for unobtrusive and continuous monitoring of a multiple relevant bioparameters. These are meant to guide the medical professionals in appropriately adapting the treatment and fine-tune the ventilation. However, synchronization phenomena of different origin (neurological, mechanical, ventilation parameters) may occur, which vary among patients, and during the course of monitoring of a single patient, the timely recognition of which is challenging even for experts. The dynamics and complex causal relations among bioparameters and the ventilation synchronization are not well studied. The purpose of this work is to elaborate on a methodology toward modeling the ventilation synchronization failures based on the evolution of monitored bioparameters. Principal component analysis is employed for the transformation into a small number of features and the investigation of repeating patterns and clusters within measurements. Using these features, nonlinear prediction models based on support vector machines regression are explored, in terms of what past knowledge is required and what is the future horizon that can be predicted. The proposed model shows good correlation (over 0.74) with the actual outputs, constituting an encouraging step toward understanding of ICU ventilation dynamic phenomena.

Ineffective efforts in ICU assisted ventilation: Exploring causalities via multiscale analysis.

Intensive Care Unit (ICU) is a data intensive environment, requiring continuous monitoring of patient's physiology and response to treatment. In assisted ventilation, where patient effort that triggers the ventilator and there is need for patient-ventilator coupling, attention is required in cases where patient's effort that doesn't trigger the ventilator at all. When synchronization between the patient's attempt to breath and the assisted ventilation event is lost, an ineffective effort (IE) event takes place. A series of relevant bioparameters continuously monitored, are meant to guide the medical professionals in appropriately adapting the operation and treatment, in order to minimize IEs. The purpose of this work is to investigate the causal relations between physiological or ventilation parameters and IE events. A multiscale approach is proposed, based on wavelet similarity and localized phase relationship. The proposed method indicates the existence of distinct frequency zones correlated with the IE experienced by the patient.

Hepatocellular carcinoma with invasion into the right atrium. Report of two cases and review of the literature.

We report two rare cases of hepatocellular carcinoma with invasion into the right atrium. In both our cases, the patients had liver cirrhosis and were admitted to our department due to symptoms such as worsening of the jaundice, ascites and edema of the lower extremities. The diagnosis of the HCC was established when we found high levels of alpha-fetoprotein, and the patients underwent MRI and CT-scan that were indicative of HCC. The clinical suspicion of invasion of the RA by the tumor emerged from the presence of heart-related symptoms, such as dyspnea and chest discomfort. The patients underwent two-dimensional transthoracic echocardiogram, which revealed from the sub-costal view a mobile atrial mass protruding from the inferior vena cava. In conclusion, when a patient with a history of chronic hepatic disease presents with symptoms of right heart failure one must be cautious and should bear in mind that right heart involvement from a malignant tumor may be present.

Wild chamomile (Matricaria recutita L.) mouthwashes in methotrexate-induced oral mucositis.

Oral mucositis is a known complication of methotrexate (MTX) therapy, but a single efficacious intervention or agent for prophylaxis or management of this side effect has not yet been identified. We report a case of MTX-induced oral mucositis in a patient with rheumatoid arthritis, who was successfully treated with Wild chamomile mouthwashes.

Effect of antihypertensive treatment on lipids and fibrinogen: Greek multicentre study of cilazapril.

The effect cilazapril (CLZ) treatment on serum lipids and fibrinogen was studied in 114 hypertensive patients for 18 weeks. Blood pressure, heart rate, lipid profile and fibrinogen were measured before and at the end of the study in all patients. Satisfactory blood pressure control was seen in 68% of the patients (group A) after 4 weeks of treatment with 5 mg CLZ monotherapy, while a single dose of chlorthalidone, 25 mg daily, was added to the therapeutic regimen of the remaining 32% of patients (group B) to achieve blood pressure control. We conclude that CLZ has a slight beneficial effect on the lipid profile and a significantly beneficial effect on fibrinogen, but its combination with a diuretic reverses this beneficial effect.

Vascular endothelium, mechanical properties of the arterial wall and local angiotensin converting enzyme inhibition.

METHODS: An experimental model of in situ isolated carotid arteries was used to study the contribution made by angiotensin II (Ang II) towards the mechanical properties of the arterial wall in 12-week-old Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats. The effects of local incubation with saralasin (Sar1-Thr8-Ang II, 10(-6) mol/l) and with lisinopril (5 x 10(-6) mol/l) on carotid compliance were compared to the effects of removing the endothelium and the effects of totally abolishing vasomotor tone with potassium cyanide (0.1 mg/ml). RESULTS: With an intact endothelium, local incubation with lisinopril increased carotid compliance by 23% in WKY rats (P less than 0.05) and by 14% in SHR (P less than 0.01). Under the same experimental conditions, saralasin increased carotid compliance by 24% in WKY rats and 23% in SHR relative to control values (P less than 0.05 and P less than 0.001, respectively). Removal of the endothelium induced significant increases in carotid compliance in WKY rats (17%, P less than 0.01) and in SHR (33%, P less than 0.001). After removal of the endothelium, there was no further increase in carotid compliance with lisinopril in either strain. In contrast, saralasin induced further significant compliance increases in both strains (+18%, P less than 0.001, and +11%, P less than 0.01, in WKY and SHR, respectively). After the artery had been poisoned with potassium cyanide, there was no further increase in compliance relative to values obtained with saralasin in either strain with or without the endothelium. CONCLUSIONS: These findings suggest that Ang II receptors have a major effect on the control of basal vasomotor tone of large arteries in both normotensive and hypertensive rats. Furthermore, the increase in carotid compliance induced by local incubation with saralasin and with angiotensin converting enzyme (ACE) inhibitors may involve similar mechanisms acting on smooth muscle angiotensin receptors.

Precordial ECG mapping in acute myocardial infarction (AMI) after intravenous infusion of streptokinase (s).

Repeated precordial ECG mapping (42 leads) and CK-MB serum measurements were done in 40 patients with anterior and/or anterolateral acute myocardial infarction. Twenty patients serving as controls, were treated with routine anticoagulant therapy. In 20 patients (the s group), randomly selected, a short-term IV infusion of 1,500,000 IU streptokinase was administered and followed by the same anticoagulant treatment as in controls. Ten subjects from each group underwent coronary arteriography one month later. From the analysis of ECG mapping the number of leads (N) and the sum of measurements (sigma) for each parameter were calculated. Before treatment there were no significant differences for all measured parameters between the two groups of patients. Seven days later, ST elevations were statistically different for NST and sigma ST with lower values for the s group. Higher values for NR and sigma R were also noted in this group. No statistically significant difference was found for NQ and sigma Q. CK-MB curve showed an earlier peak in the s group than in the control group. Five patients from the s group showed a patency of the infarct-related vessel. In conclusion, the results of this study show that patients receiving s have a significant benefit with ECG improvement. On the other hand, the CK-MB curve indicates an eventual recanalization to a certain degree in the obstructed coronary artery, which is the final goal.

Cardiac hypertrophy and characteristic impedance in spontaneously hypertensive rats.

Characteristic impedance and systemic arterial compliance were evaluated in 12 anaesthetized spontaneously hypertensive rats (SHR) from analysis of phasic records of pressure and flow in the ascending aorta. Cardiac hypertrophy expressed as the ratio of the left ventricular weight to the body weight was not correlated with arterial blood pressure (systolic, diastolic or mean). In contrast, there was a significant relationship between the left ventricular weight to body weight ratio and the characteristic impedance, suggesting that increased arterial stiffness contributes to left ventricular hypertrophy in SHR.

Relationships between single-vessel coronary artery obstructions and wall motion dysfunction analyzed by four computer-based methods.

We analyzed regional wall motion in 238 patients by using cineangiograms recorded in the 30 degrees right anterior oblique projection. The sample was divided into three groups: a normal group (n = 71), a group with isolated obstruction of the left anterior descending coronary artery and previous anterior myocardial infarction (n = 85), and a group with isolated obstruction of the right coronary artery and previous inferior myocardial infarction (n = 82). Both anterior and inferior groups also had motion abnormality within the corresponding anterior or inferior wall as judged by the qualitative analysis of cineangiograms. Four quantitative methods were compared: a long axis method and a center of mass method using internal reference systems, a method derived from the Stanford model and an area-based method using external reference systems. Normal regional values were determined from the normal group to evaluate the specificity and sensitivity of the methods. The area-based method was the most sensitive in the anterior infarction group, whereas the center of mass method was the most sensitive in the inferior infarction group. We conclude that there is no evidence that any method, among those tested, is superior to others for every expected location of wall motion abnormality.

[Pathogenesis of tachycardia in hyperthyroidism. Value of Holter monitoring and the use of a beta-blocker]. / Pathogénie de la tachycardie de l'hyperthyroïdie. Intéret de l'enregistrement Holter et de l'utilisation d'un beta-bloqueur.

The mechanisms of tachycardia in hyperthyroidism were investigated by means of Holter recordings of heart rate in 45 patients, 33 of whom had sinus rhythm and were left untreated. In the remaining 12 patients, recordings were taken after 3 days of treatment with either propranolol (120 mg/day; 6 patients) or pindolol (15 mg/day; 6 patients). Propranolol is a beta-blocker devoid of intrinsic sympathetic activity whereas pindolol possesses such activity. Changes in heart rate under the influence of each of these drugs were compared with those observed in 96 controls similarly treated. The difference in baseline heart rare between day and night was significantly higher (p less than 0.01) in patients with hyperthyroidism (17 +/- 1 QRS/min) than in controls (13 +/- 1 QRS/min). Day and night heart rates were increased by pindolol, the increase in night heart rate being significantly greater (p less than 0.05) in patients with hyperthyroidism (23.4 +/- 4.9%) than in controls (11.6 +/- 2.6%). These results suggest that sinus tachycardia in hyperthyroidism is related to an increase in the number of myocardial beta-adrenoceptors. They also indicate that thyrotoxicosis should not be treated with beta-blockers possessing intrinsic sympathetic activity.

Ventricular function and arterial compliance in patients with congestive cardiomyopathy.

In order to study the interrelationship between left ventricular afterload, estimated from the mean left ventricular wall stress, and the mechanical properties of the aorta, we have simultaneously measured systemic arterial compliance and left ventricular wall stress in 19 patients with congestive cardiomyopathy. The strong linear relationship between the ejection fraction of the left ventricle and systemic arterial compliance, and between left ventricular wall stress and systemic arterial compliance, suggests that systemic arterial compliance is an important determinant of left ventricular afterload and thus of left ventricular function.

[Value of long-term electrocardiography in patients with cerebral ischemic accidents]. / Intérêt d'un électrocardiogramme de longue durée chez les patients ayant eu un accident cérébral ischémique.

Continuous 24 hour electrocardiography (Holter monitoring) was performed in 226 patients aged 20 to 85 years (mean 61 years) presenting with focal signs of a cerebrovascular accident (CVA). The technique was the same in all patients; the study was limited to paroxysmal atrial arrhythmias. Eighty four of the 226 patients examined had atrial arrhythmias which were already known in 39 patients before Holter monitoring. In the other 187 cases, the following results were obtained: 1) 9 patients (4,8%) had paroxysmal atrial fibrillation (AF), 2) 6 patients (3,2%) had paroxysmal atrial tachycardia (PAT), 3) 11 patients (5,9%) had runs of atrial extrasystoles, 4) 19 patients (10%) had isolated atrial extrasystoles (IAE). When patients with underlying cardiac disease constituting a diagnostic indicator for arrhythmia were excluded, the following incidences were obtained: AF = 3,7%, PAT = 2,7% and runs of atrial extrasystoles = 4,3%. The majority of these arrhythmias occurred in elderly patients in whom atrial arrhythmias are known to occur and may be asymptomatic. There were practical consequences of these results, i.e. antiarrhythmic and anticoagulant therapy in 12 patients (6,4%) alone. As Holter monitoring is also associated with a number of false negative results with respect to paroxysmal atrial tachycardia, we do not believe that this investigation should be offered routinely to patients with CVA in the absence of other clinical or electrocardiographic indications.

Systemic arterial compliance in patients with non obstructive cardiomyopathy (NOCM), and coronary artery disease (CAD).

Arterial compliance had been estimated in three groups of patients: control, NOCM, and CAD, from analysis of the arterial pressure curve. In the three groups, a simple first order Winkessel model had been validated during normal and post extrasystolic beats. The measured arterial compliance depends mainly on i the diastolic pressure, ii, the mechanical properties of the aorta and major arteries. For the same range of age and diastolic pressure, the arterial compliance was not significantly different in the three groups of patients. Because of the significant variations of the arterial compliance during slight modifications of the diastolic pressure, the lack of difference in the compliance of control, NOCM, and CAD patients may be attributed to similar arterial mechanical properties.

[Evaluation of left ventricular function in diabetics by studying systolic time intervals]. / Evaluation de la fonction ventriculaire gauche chez les diabétiques par l'étude des intervalles de temps systoliques.

Systolic time intervals were measured before and four minutes after maximal exercise stress testing in 54 patients without obvious cardiac disease. Twenty seven patients (average age 46 years) had diabetes of over 5 years standing (group II); group I comprised 27 normal controls (average age 46 years). All patients underwent maximal treadmill stress testing using the Bruce protocol and the maximal heart rate was achieved without any signs of coronary insufficiency. No significant difference was observed in the basal systolic time intervals of the two groups. The difference was not significant 4 minutes after the stress test. However, when the changes before and after exercise were compared, the patients in group I had a significant increase in heart rate (p less than 0,001), a reduction in the duration of electromechanical systole (QB2; p less than 0,02) in the preejectional period (PEP; p less than 0,001) and in the PEP/LVET ratio: p less than 0,01, whilst left ventricular ejection time (LVET) remained unchanged. The patients in group II only showed an increase in heart rate (p less than 0,01) and LVET (p less than 0,001). The differences in the systolic time intervals after exercise between these two groups probably reflect a degree of cardiac dysfunction which is not apparent at rest.

[Effect of nitroglycerin and N-ethoxycarbonyl-3-morpholinosydnonomine on the walls of large arteries]. / Action de la nitroglycérine et de la N. éthoxycarbonyl-3-morpholinosydnonimine sur les parois de gros troncs artériels.

Systemic arterial compliance was measured in 20 patients with left ventricular failure due to congestive cardiomyopathy. The method consisted in evaluating arterial compliance by analysing the exponential fall of the arterial pressure curve on a simple visco-elastic model. In the patient group, significant correlations were found between arterial compliance and age (r = 0,64 ; p less than 0,01) and arterial compliance and systolic blood pressure (r = -0,58 ; p less than 0,001). These relationships suggest that arterial compliance depends on the height of the systolic blood pressure and/or the elasticity of the arterial walls. Two groups of patients were defined : Group I (10 patients) given a single oral dose of 7,5 mg of nitroglycerine (Lenitral), and Group II (10 patients) giben a single oral dose of 4 mg N ethoxycarbonyl-3-morpholinosydnonomine (Molsidomine). There was no significant difference in the hemodynamic parameters or arterial compliance between the two groups before administration of these drugs. However, systolic blood pressure was significantly lower (p less than 0,01) and compliance significantly higher (p less than 0,05) after treatment in Group II. In Group I, nitroglycerine caused a significant increase in compliance (p less than 0,01), a significant decrease in systolic (p less than 0,02) and mean blood pressure (p less than 0,05) whilst heart rate, cardiac output and total systemic resistance remained unchanged. In Group II, Molsidomine caused a significant increase in arterial compliance (p less than 0,01), a decrease in systolic (p less than 0,001), diastolic (p less than 0,01) and mean blood pressure (p less than 0,01) and in cardiac output (p less than 0,01), whilst heart rate and total systemic resistance remained unchanged. This study shows that both drugs studied had significant effects on the walls of the large arteries.