Iloprost infusion does not reduce oxidative stress in systemic sclerosis

Systemic sclerosis is a connective tissue disease in which oxidative stress represents an important player among the complex pathogenetic mechanisms of the disease. Iloprost, an analogue of natural prostacyclin, is used in systemic sclerosis for the treatment of severe Raynaud’s phenomenon and ischemic ulcers. There is a clear evidence that iloprost attenuates oxidative damage induced by ischemia–reperfusion phenomena. The aim of this study is to evaluate the effect of iloprost on oxidative status in ten patients with systemic sclerosis by measuring urinary levels of 8-isoprostaglandin-F_2α, a member of F₂-isoprostanes. We found that systemic sclerosis patients cyclically treated with iloprost showed increased urinary level of 8-isoprostaglandin-F_2α in comparison with healthy subjects; urinary 8-isoprostaglandin-F_2α did not diminish soon after the iloprost infusion as well as 3, 15 and 30 days after the drug administration. Unlike experimental studies, in vivo the strong vasodilator effect of iloprost infusion did not reduce oxidative status.     

Bacteriology and beta-lactamase activity in acute exacerbation of chronic bronchitis.

OBJECTIVES: To assess the bacteriology of beta-lactamase (BL) enzyme activity in sputum of 40 patients with acute exacerbation of chronic bronchitis (AECB). METHODS: The microbiology, BL production by the different isolates, and BL contents in the sputum were determined. RESULTS: Eighty-four isolates were recovered (2.1 isolates per specimen), 44 aerobic and facultative (1.1 isolates per specimen), and 40 anaerobic (1.0 isolate per specimen). Aerobic bacteria were recovered in only 9 (22.5%) specimens, anaerobic bacteria in 9 (22.5%), and mixed aerobic and anaerobic bacteria were found in 22 (55%). The predominant aerobic isolates were Streptococcus pneumoniae (15 isolates), Haemophilus influenzae (11), Moraxella catarrhalis and Klebsiella pneumoniae (4 each). The predominant anaerobes were Peptostreptococcus sp. (19), Prevotella sp. (11), and Fusobacterium sp.(6). Mixed flora were present in 25 (62.5%) specimens, and the number of isolates varied from 2 to 5 per specimen. Thirty-nine beta-lactamase-producing bacteria (BLPB) were isolated in 33 (82.5%) of the 40 cases. The predominant aerobic BLPB were H. influenzae, M. catarrhalis, K. pneumoniae, Staphylococcus aureus, and Escherichia coli. The predominant anaerobic BLPB were Prevotella sp. and Fusobacterium sp. Beta-lactamase activity was detected in 26 (79%) of 33 of specimens in which BLPB were isolated, and in none of the seven specimens that did not harbor BLPB. CONCLUSIONS: The rapid detection of BL activity in sputum specimens may have implications for the antimicrobial management with AECB.     

Review: Antiplatelet therapy does not reduce mortality in chronic kidney disease

QUESTION What are the effects of antiplatelet therapy on mortality and cardiovascular (CV) events in patients with chronic kidney disease (CKD)? REVIEW SCOPE Included studies compared antiplatelet agents with control (placebo, standard care, or no treatment) in adults with CKD. Trials with follow-up <?2 months in duration and those that did not provide data in an extractable format were excluded. Outcomes were mortality, CV events, and bleeding. REVIEW METHODS EMBASE/Excerpta Medica (1980 to Nov 2011), Cochrane Central Register of Controlled Trials (2011, Issue 4), Cochrane Renal Group's specialized register (Nov 2011), and reference lists of retrieved publications were searched for randomized controlled trials (RCTs). Investigators were contacted. 27 RCTs (n =?10?973) of patients with stable or no CV disease met the section criteria. Median follow-up was 12 months. Study quality was low to moderate as assessed by the Grading of Recommendations Assessment, Development, and Evaluation guidelines. MAIN RESULTS Meta-analysis showed that antiplatelet therapy reduced risk for myocardial infarction and increased minor bleeding (Table). Groups did not differ for all-cause mortality, CV mortality, stroke, or major bleeding (Table). CONCLUSION In patients with chronic kidney disease, antiplatelet therapy reduces myocardial infarction, but not mortality, and increases minor bleeding.Antiplatelet therapy vs control in patients with chronic kidney disease and stable or no cardiovascular disease*OutcomesNumber of trials (n)Weighted event ratesAt a median 12 moAntiplateletsControlRRR (95% CI)NNT (CI)All-cause mortality21 (10?632)6.2%7.2%13% (-24 to 39)Not significantCardiovascular mortality16 (8706)3.4%3.8%9% (-36 to 40)Not significantMyocardial infarction10 (9133)2.2%3.3%34% (13 to 49)89 (62 to 232)Stroke10 (9133)1.3%2.0%34% (-178 to 84)Not significantRRI (CI)NNH (CI)Major bleeding18 (10?230)1.6%1.3%29% (-31 to 142)Not significantMinor bleeding8 (7202)12%6.9%70% (44 to 102)21 (15 to 34)*Abbreviations defined in Glossary. RRR, RRI, NNT, NNH, and CI calculated from control event rates and relative risks in article using a random-effects model.     

Prulifloxacin: a new fluoroquinolone for the treatment of acute exacerbation of chronic bronchitis

Empiric therapy with oral antibiotics is normal practice in the treatment of acute exacerbations of chronic bronchitis (AECB), but there is growing concern regarding efficacy of the currently available antimicrobials. Prulifloxacin, the lipophilic prodrug of ulifloxacin, is an oral fluoroquinolone antibacterial agent with a broad-spectrum in vitro activity against Gram-negative and -positive bacteria, and a long elimination half-life, which allows the once-daily administration. In addition, it penetrates extensively into lung tissues. Statistical analyses indicated a significant linear trend between the prulifloxacin 300, 450, and 600 mg doses, which would point to an interesting relationship between dose employed and response obtained. The 600 mg once-daily dose showed the best risk/benefit ratio, and was selected for use in the pivotal clinical trials. In well-designed clinical trials, prulifloxacin 600 mg administered once daily for 10 days in patients with AECB showed good clinical and bacteriological efficacy (similar to that of ciprofloxacin or co-amoxiclav). In particular, the clinical response rates were favourable in all clinical trials, with eradication rates in patients with pneumococcal infections at least as high as the comparators. It can be concluded that prulifloxacin 600 mg once daily is a new therapeutic prospect in the antimicrobial therapy of AECB. In particular, since good patient compliance is a key factor in the successful treatment of any infection, the once daily treatment with prulifloxacin may have some compliance advantages compared to the twice-daily treatment with agents such as ciprofloxacin or co-amoxiclav.     

Aging does not reduce heat shock protein 70 in the absence of chronic insulin resistance

Heat shock protein (HSP)70 decreases with age. Often aging is associated with coincident insulin resistance and higher blood glucose levels, which also associate with lower HSP70. We aimed to understand how these factors interrelate through a series of experiments using vervet monkeys (Chlorocebus aethiops sabaeous). Monkeys (n = 284, 4-25 years) fed low-fat diets showed no association of muscle HSP70 with age (r = .04, p = .53), but levels were highly heritable. Insulin resistance was induced in vervet monkeys with high-fat diets, and muscle biopsies were taken after 0.3 or 6 years. HSP70 levels were significantly greater after 0.3 years (+72%, p < .05) but were significantly lower following 6 years of high-fat diet (-77%, p < .05). Associations with glucose also switched from being positive (r = .44, p = .03) to strikingly negative (r = -.84, p < .001) with increasing insulin resistance. In conclusion, a low-fat diet may preserve tissue HSP70 and health with aging, whereas high-fat diets, insulin resistance, and genetic factors may be more important than age for determining HSP70 levels.     

Pharmacodynamics of levofloxacin in patients with acute exacerbation of chronic bronchitis

STUDY OBJECTIVES: Levofloxacin is a fluoroquinolone antimicrobial agent for which pharmacodynamic relationships between the maximum serum antibiotic concentration (Cmax)/minimum inhibitory concentration (MIC) ratio and/or the area under the serum concentration-time curve during a 24-h dosing period (AUC(0-24))/MIC ratio and clinical and/or microbiological outcomes have been developed. In this study we examined the relationship between the in vitro bacterial susceptibility to levofloxacin, the achieved levofloxacin serum and sputum concentrations, and the in vivo bacterial eradication in patients with acute exacerbations of chronic bronchitis. PATIENTS AND INTERVENTIONS: Thirty patients received levofloxacin, 500 mg/d po for 7 days. Samples of venous blood and sputum for the determination of levofloxacin concentrations were collected on day 1 immediately prior to dosing, and then at 1, 4, 8, 12, and 24 h. RESULTS: The mean peak concentration in serum (6.5 mg/L) was found 1 h after administration, and at 4 h after administration in sputum (5.1 mg/L). Levofloxacin was always detectable 24 h after administration from both samples. Successful treatment occurred in 90% (27 of 30 patients) when assessed both clinically and bacteriologically. Treatment was successful in eight patients when the AUC(0-24)/MIC ratio was > 40 for serum, and in nine patients when it was > 30 for sputum. Treatment was also successful in seven patients when the Cmax/MIC ratio was > 5.01 for serum, and in nine patients when the Cmax/MIC ratio was > 4.01 for sputum. Treatment was successful in 90% (27 of 30 patients) when the AUC(0-24)/MIC ratio was > 125 for serum and > 100 for sputum, and when Cmax/MIC was > 10.01 for serum and > 8.01 for sputum following the first dose. CONCLUSIONS: The pharmacodynamics values that we have obtained in sputum with levofloxacin may be used as predictors of therapy outcomes.     

Pulmonary and systemic hemodynamic evolution in chronic bronchitis

Hemodynamic values obtained during right heart catheterization in about 35 patients with chronic bronchitis were compared with the same variables 3.3 years later (range, 2 to 5 years). In the group of 13 patients with mean pulmonary arterial pressure less than 20 mm Hg at the first catheterization, the average value was 15.8 mm Hg at rest and 25.2 mm Hg during moderate exercise at the first investigation, and 16.9 and 26.3 mm Hg, respectively at the second catherization; the changes were not significant. In the group of pulmonary hypertensive patients, the mean pulmonary arterial pressure was 27.0 mm Hg at rest and 44.1 mm Hg during moderate exercise at the first catheterization, and 26.8 and 38.9 mm Hg, respectively, at the second catheterization. Thus, even in this group, there was no deterioration in pulmonary hemodynamics, because there was no significant change in right or left filling pressure, or in cardiac output. There was, however, a marked decrease in systemic arterial pressure, which was significant in the group with pulmonary hypertension. This decrease in left ventricular afterload could be partly responsible for the stabilization of pulmonary hemodynamics, and it could be due to the peripheral vasodilating effect of hypoxia and hypercapnia.     

In patients with chronic bronchitis a four week trial with inhaled steroids does not attenuate airway inflammation

Systemic corticosteroids have been recommended as a therapeutic option in patients with moderate to severe COPD. In an early stage of the disease, i.e. chronic bronchitis with mild or no airflow obstruction, a trial with inhaled steroids could reveal potential benefits, particularly in terms of a modulation of airway inflammation. We therefore investigated the effect of inhaled fluticasone (1000 microg day(-1)) on markers of airway inflammation in 19 patients with chronic bronchitis (mean+/-SEM FEV1, 83.4+/-3.0% predicted; FEV1/VC, 67.5+/-2.4%) in a double-blind, cross-over, placebo-controlled manner. Visits were performed before and after two 4-week treatment periods. separated by a 4-week washout period. Lung function, the concentration of exhaled nitric oxide, differential cell counts in induced sputum and the number of cells positive for iNOS, as well as the levels of LDH, ECP, neutrophil elastase and IL-8 in sputum supernatants were determined. Although the total cell number decreased significantly after fluticasone (geometric mean 12.3 vs. 7.7 x 10(6)/ml; P<0.05) it was not significantly different from the change observed after placebo (14.2 vs. 10.6 x 10(6)/ml; n.s.). None of the other parameters showed statistically significant changes after fluticasone or placebo and the results did not depend on the presence of airway hyperresponsiveness. We conclude that in patients with chronic bronchitis short-term treatment with inhaled corticosterids did not improve lung function or inflammatory parameters to an extent which was statistically significant as compared to spontaneous variability.     

Sildenafil citrate does not reduce exercise tolerance in men with erectile dysfunction and chronic stable angina.

AIMS: The aim of this study was to evaluate whether sildenafil, used for treatment of erectile dysfunction (ED), affects the exercise tolerance and ischaemic threshold in men with exercise-induced angina not taking nitrates. METHODS: This was a double-blind placebo-controlled study in men with ED and chronic stable angina, assessing the effect of sildenafil on time to limiting angina during incremental treadmill exercise. Patients remained on their antianginal therapy and received a 100-mg dose of sildenafil or placebo 1h prior to treadmill exercise. Other measurements included times to onset of angina, 1-mm ST-segment depression, and total exercise time. RESULTS: Adjusted treatment differences for the time to limiting angina, time to onset of angina, total exercise time, and time to 1-mm ST-segment depression were (mean+/-SE) 20+/-10s (95% CI, 1-39; P=0.040), 32+/-11s (95% CI, 11-53; P=0.004), 20+/-10s (95% CI, 0-39; P=0.049), and 12+/-17s (95% CI, -21 to 45, P=0.48), respectively, in favour of sildenafil. There were no serious treatment-related adverse events. CONCLUSIONS: Sildenafil was well tolerated and did not adversely affect any exercise parameter in men with coronary artery disease and ED. Favourable trends in total exercise duration and times to onset of angina and limiting angina were recorded with sildenafil use.     

Somatostatin does not reduce oesophageal variceal pressure in liver cirrhotics.

Transmural oesophageal variceal pressure was determined by direct puncture of the varices in 27 patients with liver cirrhosis and oesophageal varices. Variceal pressure was not influenced three to six minutes after somatostatin bolus administration and slightly increased during somatostatin infusion. Thus, potential haemostatic benefits of somatostatin cannot be explained by pressure reductions in the varices.     

Evaluation of systemic host defense mechanisms in chronic bronchitis

Seventy-six chronic bronchitis patients were studied in order to determine the possible presence of disorders in their systemic defense mechanisms. No significant difference in lymphocyte subsets, in serum immunoglobulin and complement component (C3 and C4) levels was found in chronic bronchitis patients compared to normal adult controls. Skin tests for delayed hypersensitivity revealed a high frequency (39%) of hypoergic patients (with 1-2 positive reactions) in comparison to normal subjects. Altered values of many functional properties of both neutrophils and monocytes were demonstrated. The percentage of patients with intermediate (between 1 and 2 SD below the mean of controls) and defective (lower than 1.96 SD) values of chemotaxis, phagocytosis index and Candida killing was about 50%. Phagocytosis frequency and nitroblue tetrazolium reduction frequency were less frequently impaired.     

Acute exacerbation of chronic bronchitis: need for an evidence-based approach

Acute exacerbations of chronic bronchitis (AECB) can be classified into three levels according to severity: (1) home treatment sufficient; (2) hospitalisation required; (3) hospitalisation in the presence of respiratory failure. This evidence-based classification is useful in ranking the clinical relevance of the episode and its outcome, and makes it possible to define the clinical history, clinical evaluation and diagnostic procedures of an exacerbation. Treatment guidelines vary according to severity, but they are essentially based on appropriate bronchodilator therapy (beta(2) agonists and/or anticholinergics, corticosteroids and antibiotics selected according to the local bacterial resistance pattern). It is important that cases requiring management in an intermediate/special respiratory care unit or intensive care unit (ICU) be identified. This is the stage where oxygen therapy and ventilatory support become particularly important. As first choice, they should be non-invasive, saving intubation and invasive ventilatory support for most severe cases characterised by severe acidemia and hypercapnia. We identify the optimal criteria for hospital discharge and follow-up of patients with AECB. In view of the chronic nature of the underlying disease, a correct follow-up is essential to avoid frequent and repeated relapses.     

Prulifloxacin: a brief review of its potential in the treatment of acute exacerbation of chronic bronchitis

Exacerbations of chronic bronchitis (AECB) are a major cause of morbidity and mortality in patients with chronic obstructive pulmonary disease (COPD), and their impact on public health is increasing. The new fluoroquinolones have an excellent spectrum providing cover for the most important respiratory pathogens, including atypical and “typical” pathogens. Not surprisingly, different guidelines have inserted these agents among the drugs of choice in the empirical therapy of AECB. The pharmacokinetic and dynamic properties of the new fluoroquinolones have a significant impact on their clinical and bacteriological efficacy. They cause a concentration-dependent killing with a sustained post-antibiotic effect. This review discusses the most recent data on the new fluoroquinolone prulifloxacin and critically analyses its activity and safety in the management of AECB.     

Bacteriological findings in the transtracheal aspirate from patients with acute exacerbation of chronic bronchitis

Summary Transtracheal aspirates from 87 patients with acute exacerbations of chronic bronchitis who had received no recent antibiotic treatment were examined. A single bacterial species was found in 83% of positive cultures. Predominant pathogens wereHaemophilus influenzae andStreptococcus pneumoniae which occurred jointly or separately in 50% of positive cultures. Bacteria traditionally considered as non-pathogenic for the lower respiratory tract also appeared to play an aetiological role.Enterobacteriaceae and anaerobes were infrequent. No bacterial growth was found in 11 cases.

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Bakteriologischer Befund im Transtrachealaspirat von Patienten mit akuter Exazerbation einer chronischen Bronchitis

Zusammenfassung Das Transtrachealaspirat von 87 Patienten mit antibiotisch unbehandelter, akuter Exazerbation einer chronischen Bronchitis wurde bakteriologisch untersucht. In 83% der positiven Kulturen wurde nur eine Bakterienart nachgewiesen. Die weit vorwiegenden Befunde warenHaemophilus influenzae undStreptococcus pneumoniae die, vereinzelt oder gemeinsam, in 50% der positiven Kulturen auftraten. Auch Bakterienspezies, die in bezug auf die Luftwege gewöhnlich als nicht pathogen betrachtet werden, waren anscheinend von ätiologischer Bedeutung.Enterobacteriaceae und Anaerobier wurden selten isoliert. In 11 Fällen wurden keine Bakterien nachgewiesen.

     

Low dose desensitisation does not reduce the toxicity of sulphasalazine in rheumatoid arthritis.

OBJECTIVE: To examine the proposal that pretreatment low dose desensitisation may reduce the incidence of toxicity of sulphasalazine in the treatment of rheumatoid arthritis (RA). METHODS: A double blind, placebo controlled trial was performed with 422 patients satisfying the American College of Rheumatology criteria for RA who required sulphasalazine treatment because of increased disease activity. Patients received either sulphasalazine desensitisation, or placebo, for three weeks before commencement of sulphasalazine treatment. The frequency and nature of adverse effects and changes in clinical and laboratory parameters of disease activity were measured after three and six months. RESULTS: Improvement in the efficacy of sulphalasazine (measured by clinical and laboratory parameters) was significant and similar in magnitude in both groups. There was no significant difference between actively and placebo desensitised patients as regards the incidence or profile of adverse effects (toxicity). CONCLUSION: Pretreatment low dose desensitisation is unhelpful in reducing the toxicity associated with sulphasalazine treatment of RA.     

Quality of life in acute exacerbation of chronic bronchitis: results from a German population study

This study reports on data from a study conducted in the Federal Republic of Germany examining the quality of life (QoL) of patients with chronic bronchitis (CB) and its acute exacerbations (AECB). Data from 320 patients were collected at AECB and subsequently during a stable phase (non-AECB) utilizing the St George's Respiratory Questionnaire (SGRQ) and the Nottingham Health Profile (NHP). As expected, the QoL of CB patients was poor, even at non-AECB, with patients reporting lower scores than patients with other chronic conditions. Patients reported significantly poorer QoL at AECB than at non-AECB. After adjusting for the severity of the underlying condition, poorer QoL at AECB was significantly and independently associated with older age, unemployment, increasing BMI, increasing number of prior AECBs, and Anthonisen AECB grade.While younger subjects reported significantly greater deterioration in QoL at AECB, the factors most consistently and independently associated with relative QoL deterioration at AECB were the number of prior AECBs and exposure to air pollution at home. In conclusion, this study highlights the detrimental effect of CB, and in particular AECB, on QoL.The association between QoL and patient reports of previous AECB number and air pollution are consistent with reports from other studies.