Prevalence and clinical associations of wheezes and crackles in the general population: the Tromsø study.

BACKGROUND: Wheezes and crackles are well-known signs of lung diseases, but can also be heard in apparently healthy adults. However, their prevalence in a general population has been sparsely described. The objective of this study was to determine the prevalence of wheezes and crackles in a large general adult population and explore associations with self-reported disease, smoking status and lung function. METHODS: We recorded lung sounds in 4033 individuals 40 years or older and collected information on self-reported disease. Pulse oximetry and spirometry were carried out. We estimated age-standardized prevalence of wheezes and crackles and associations between wheezes and crackles and variables of interest were analyzed with univariable and multivariable logistic regressions. RESULTS: Twenty-eight percent of individuals had wheezes or crackles. The age-standardized prevalence of wheezes was 18.6% in women and 15.3% in men, and of crackles, 10.8 and 9.4%, respectively. Wheezes were mostly found during expiration and crackles during inspiration. Significant predictors of expiratory wheezes in multivariable analyses were age (10 years increase - OR 1.18, 95%CI 1.09-1.30), female gender (1.45, 1.2-1.8), self-reported asthma (1.36, 1.00-1.83), and current smoking (1.70, 1.28-2.23). The most important predictors of inspiratory crackles were age (1.76, 1.57-1.99), current smoking, (1.94, 1.40-2.69), mMRC ≥2 (1.79, 1.18-2.65), SpO2 (0.88, 0.81-0.96), and FEV1 Z-score (0.86, 0.77-0.95). CONCLUSIONS: Nearly over a quarter of adults present adventitious lung sounds on auscultation. Age was the most important predictor of adventitious sounds, particularly crackles. The adventitious sounds were also associated with self-reported disease, current smoking and measures of lung function. The presence of findings in two or more auscultation sites was associated with a higher risk of decreased lung function than solitary findings.

Large variability in clinical judgement and definitions of left bundle branch block to identify candidates for cardiac resynchronisation therapy.

BACKGROUND: Left bundle branch block (LBBB) morphology is associated with improved outcome of cardiac resynchronisation therapy (CRT) and is an important criterion for patient selection. There are, however, multiple definitions for LBBB. Moreover, applying these definitions seems subjective. We investigated the inter- and intraobserver agreement in the determination of LBBB using available definitions, and clinicians' judgement of LBBB. METHODS: Observers were provided with 12­lead ECGs of 100 randomly selected CRT patients. Four observers judged the ECGs based on different LBBB-definitions (ESC, AHA/ACC/HRS, MADIT, and Strauss). Additionally, four implanting cardiologists scored the same 100 ECGs based on their clinical judgement. Observer agreement was summarized through the proportion of agreement (P) and kappa coefficient (k). RESULTS: Relative intra-observer agreement using different LBBB definitions, and within clinical judgement was moderate (range k 0.47-0.74 and k = 0.76 (0.14), respectively). The inter-observer agreement between observers using LBBB definitions as well as between clinical observers was minimal to weak (range k 0.19-0.44 and k = 0.35 (0.20), respectively). The probability of classifying an ECG as LBBB by available definitions varied considerably (range 0.20-0.76). The agreement between different definitions of LBBB ranged from good (P = 0.95 (0.07)) to weak (P = 0.40 (0.22)). Furthermore, correlation between the different LBBB definitions and clinical judgement was poor (range phi 0.30-0.55). CONCLUSION: Significant variation in the probability of classifying LBBB is present in using different definitions and clinical judgement. Considerable intra- and inter-observer variability adds to this variation. Interdefinition agreement varies significantly and correlation of clinical judgement with LBBB classification by definitions is modest at best.

Penetration of oxytetracycline into the nasal secretions and relationship between nasal secretions and plasma oxytetracycline concentrations after oral and intramuscular administration in healthy pigs.

The penetration of oxytetracycline (OTC) in plasma and nasal secretions of healthy pigs was evaluated during the first study, in response to oral dose of 20 mg of OTC per kg of body weight (bwt) per day as a 400 mg/kg feed medication (n = 5) and to intramuscular (i.m.)-administered formulations at 10 mg/kg bwt (n = 5), 20 mg/kg bwt (n = 5), 40 mg/kg bwt (n = 5). Concentrations of OTC in plasma and nasal secretions were determined by a validated ultra-high performance liquid chromatography associated to tandem mass spectrometry method (UPLC/MS/MS). The objectives were to select the efficacy treatment and to evaluate the possibility to predict nasal secretions concentrations from those determined in plasma. The animals were housed together in each experiment. In each group, the treatment was administered once daily during 6 consecutive days, and nasal secretions and plasma were collected after 4 and 24 h at day 2 and day 6. For oral administration, only one medicated feed was prepared and distributed to all the animals together and was consumed in approximately 1 h. To meet recommendations of efficacy for OTC in nasal secretions, only the i.m. of 40 mg/kg bwt associated to an inter-dosing interval of 24 h provides and maintains concentrations in nasal secretions ≥1 µg/mL, appropriate to the MIC 50 and 90 of Pasteurella multocida and Bordetella bronchiseptica, respectively, the main pathological strains in nasal secretions. It has been demonstrated that, using a generalized linear mixed model (GLMM), OTC in the nasal secretions (µg/mL) can be predicted taking into account the OTC concentrations in plasma (µg/mL), according to the following equation: OTC(nasal secretions) = 0.28 OTC(plasma) -1.49. In a second study, the pharmacokinetic behaviour of OTC in plasma and nasal secretions of healthy pigs was investigated, after single-dose i.m. of 40 mg/kg bwt of the drug. Blood samples and nasal secretions were collected at predetermined times after drug administration. The data collected in 10 pigs for OTC were subjected to non-compartmental analysis. In plasma, the maximum concentration of drug (C(max) ), the time at which this maximum concentration of drug (T(max) ) was reached, the elimination half-life (t½) and the area under the concentration vs. time curve (AUC) were, respectively, 19.4 µg/mL, 4.0, 5.1 h and 150 µg·h/mL. In nasal secretions, C(max) , T(max) , t½ and AUC were, respectively, 6.29 µg/mL, 4.0, 6.6 h and 51.1 µg·h/mL.

Lack of efficacy of low-dose spironolactone as adjunct treatment to conventional congestive heart failure treatment in dogs.

Aldosterone plays an important role in the pathophysiology of heart failure. Aldosterone receptor blockade has been shown to reduce morbidity and mortality in human patients with advanced congestive left ventricular heart failure. This study was designed to assess the efficacy and tolerance of long-term low-dose spironolactone when added to conventional heart failure treatment in dogs with advanced heart failure. Eighteen client-owned dogs with advanced congestive heart failure due to either degenerative valve disease (n=11) or dilated cardiomyopathy (n=7) were included in this prospective, placebo-controlled, double-blinded, randomized clinical study. After initial stabilization including furosemide, angiotensin-converting enzyme inhibitors, pimobendan and digoxin, spironolactone at a median dose of 0.52 mg/kg (range 0.49-0.8 mg/kg) once daily (n=9) or placebo (n=9) was added to the treatment, and the dogs were reassessed 3 and 6 months later. Clinical scoring, echocardiography, electrocardiogram, systolic blood pressure measurement, thoracic radiography, sodium, potassium, urea, creatinine, alanine aminotransferase, aldosterone and aminoterminal atrial natriuretic propeptide were assessed at baseline, 3 and 6 months. Survival times were not significantly different between the two treatment groups. Spironolactone was well tolerated when combined with conventional heart failure treatment.

Penetration of enrofloxacin into the nasal secretions and relationship between nasal secretions and plasma enrofloxacin concentrations after intramuscular administration in healthy pigs.

The pharmacokinetic behaviour of enrofloxacin (ENRO) in plasma and nasal secretions of healthy pigs was investigated, after a single-dose intramuscular administration of 2.5 mg/kg body weight of the drug. Blood samples and nasal secretions were collected at predetermined times after drug administration. Concentrations of ENRO and its active metabolite ciprofloxacin (CIPRO) were determined in plasma and nasal secretions by high-performance liquid chromatography (HPLC). CIPRO was not detected probably because we investigated young weaned pigs. The data collected in 12 pigs for ENRO were subjected to noncompartmental analysis. In plasma, the maximum concentration of drug (C(max)), the time at which this maximum concentration of drug (T(max)) was reached, the elimination half-life (t(1/2)(beta)) and the area under the concentration vs. time curve (AUC) were, respectively, 694.7 ng/mL, 1.0 h, 9.3 h and 8903.2 ngxh/mL. In nasal secretions, C(max), T(max), t(1/2)(beta) and AUC were, respectively, 871.4 ng/mL, 2.0 h, 12.5 h and 11 198.5 ngxh/mL. In a second experiment conducted in 10 piglets, the relationship between concentrations of ENRO measured in the plasma and the nasal secretions has been determined following single-dose intramuscular administration of 2.5, 10 or 20 mg/kg body weight of the drug. It has been demonstrated that, among several variables, i.e., (1) the dose administered, (2) the time between intramuscular injection and blood sampling, (3) the age, (4) the sex, (5) the animal body weight and (6) the plasma concentration of the drug, only the latter influenced significantly the ENRO concentration in nasal secretions. Practically, using a generalized linear mixed model, ENRO concentrations in the nasal secretions (microg/mL) can be predicted taking into account the ENRO concentrations in plasma (microg/mL), according to the following equation:

Characteristics and expectations of patients with erectile dysfunction: results of the SCORED study.

In an observational study in men with erectile dysfunction (ED) consulting a general practitioner (GP) or urologist in Belgium, demographics, ED characteristics (including erection hardness score), co-morbidities and treatment expectations were evaluated using a structured questionnaire. In total, 341 GPs and 41 urologists recruited 1492 patients. Most (74%) were untreated and 25% had ED for >3 years. Considering PDE5 inhibitors, erection hardness (89%) and maintenance (92%) were considered 'very important' by most patients. Only 18% of physicians initiated discussion about ED, despite 41% of patients having >or=3 known risk factors. The questionnaire was considered helpful by 81% of GPs and 83% of their patients. Overall, patients are under-diagnosed, and physicians are reluctant to ask about ED. A questionnaire including erection hardness score is useful to facilitate discussion about ED in general practice. Erection hardness and maintenance are more important to patients as compared to fast onset or long duration of action.

Effect of different contraceptive methods on the oxidative stress status in women aged 40 48 years from the ELAN study in the province of Liege, Belgium.

BACKGROUND: Oxidative stress is associated with the development of several disorders including cardiovascular disease and cancer. Among conditions known to influence oxidative stress, the use of oral contraception (OC) in women has been a matter of ongoing discussion. METHODS: A total of 897 eligible and healthy volunteers were recruited from among the patients of 50 general practitioners participating in the ELAN study (Etude Liégeoise sur les ANtioxydants). A subsample consisting of 209 women aged 40-48 years was studied for a comprehensive oxidative stress status (OSS), including the analysis of antioxidants, trace elements and three markers of oxidative damage to lipids. Among 209 subsample, 49 (23%) were OC users (OCU), 119 (57%) non-contraception users (NCU) and 41 (20%) were intrauterine (hormonal and copper) devices users (IUD). RESULTS: After adjustment for smoking, systolic and diastolic blood pressure and BMI (or waist circumference), a marked and significant increase in lipid peroxides was observed among OCU women when compared with NCU and IUD users. A cut-off value of 660 microM in lipid peroxides allowed the discrimination of OCU from the two other groups. In contrast, no difference was observed in the plasma concentration of both oxidized low-density lipoprotein (LDL) and their related antibodies. The increased level in lipid peroxides was strongly related to higher concentrations of copper (r < 0.84; P < 0.0001, cut-off value 1.2 mg/l). When compared with NCU and IUD users, plasma antioxidant defences were significantly altered in OCU women as shown by lower levels of beta-carotene (decrease of 39%; P < 0.01) and gamma-tocopherol (decrease by 22%; P < 0.01). In contrast, higher concentrations of selenium (increased by 11.8%; P < 0.01) were observed in OCU women. Blood concentrations of vitamin C, alpha-tocopherol and zinc were unaffected by OC use. CONCLUSIONS: The intake of OC significantly increases the lipid peroxidation in women aged 40-48 years. This may represent a potential cardiovascular risk factor for these women.

The effects of short-term treatment with levamisole on cytokines in volunteers and cancer-patients.

In search for clues to the potential immunomodulating mechanism of action of levamisole which might be used as monitoring parameters, we have determined a variety of cytokines in the peripheral blood of volunteers and carcinoma patients before and after a single or a 3-day-treatment with 150 mg/day. In cancer patients no changes could be detected 4 days after a 3-day-treatment course in the levels of TNF-alpha, IL-1beta, IL-2 or IL-6. In a placebo-controlled volunteer study the same treatment did not affect the levels of beta2-microglobulin, IL-1beta, IL-1alpha, IL-2 or IL-6. However, 24hr after the last treatment the concentration of neopterin was slightly but significantly increased and the concentration of soluble IL-2 receptors decreased. A single treatment failed to produce such an effect. It is suggested that the measurement of neopterin and soluble IL-2 receptors may provide useful information in future trials.