The anti-inflammatory effects of macrolides.
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Biomedical subjects
Publications and source records attributed to M Woodhead.
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The use of antibiotics in exacerbations of chronic obstructive pulmonary disease (ECOPD) is based on the finding of potentially pathogenic bacteria in sputum samples. Antibiotics remain an important part of treatment, but the validity of this approach for all patients is now being questioned. Using bronchoscopic methods, bacteria have been found to be absent from the lower airway in up to 50% of patients during exacerbations, suggesting that antibiotics may not be essential for all ECOPD. Antibiotic studies also suggest that they influence outcome in only a subgroup of patients. For an antibiotic to be active in ECOPD, it must reach the bacteria in either airway secretions or airway cells. The lipophilicity/hydrophilicity of the molecule is an important determinant of an antibiotic's ability to do this. It must not only reach the site but also do so at a concentration greater than the minimum inhibitory concentration (MIC) of the bacterium. For some antibiotics, the peak concentration is the best determinant of response, for others the proportion of the dose interval with antibiotic concentrations above the MIC is a better correlate. Studies have been hampered by the difficulties in measuring antibiotic concentrations in the different anatomical sites within the airways. Our knowledge is currently incomplete, but the above problems may now be being overcome.
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A method is described for isolating DNA of high molecular mass (M(r)) from blackcurrant and other softfruit species. Following a hexacethylytimethyl ammonium bromide (CTAB)-based extraction procedure, samples are treated with a glycosidic hydrolase mixture and RNase, and then purified. The suitability of this DNA for Southern analysis and genomic-library construction is demonstrated.
Community-acquired lower respiratory tract infection (LRTI) is a common clinical problem, and a chest radiograph is the most common investigation. This study investigated why general practitioners (GPs) request radiographs and whether radiographic features of LRTI affect management. The 12 month study included GP-requested chest radiographs performed at the Manchester Royal Infirmary. The GPs of patients with radiographic evidence of LRTI were sent a questionnaire. Radiographs (n=2,538) were performed in patients aged >15 yrs. One hundred and eleven (4.4%) chest radiographs showed evidence of LRTI, and 97 (87%) were included in the analysis. Fifty-six (62%) had their radiograph requested at the second or third visit. Forty-five (58%) radiographs were performed to confirm infection. In 47 (48%) of cases the GP felt the radiograph had affected treatment. An effect on treatment was significantly more common in patients not receiving antibiotics prior to the radiograph. Twenty-nine (32%) of GPs felt a normal radiograph would have affected management, most often with respect to antibiotic prescriptions (17 (58%)). Where the radiologist's report suggested a repeat radiograph or hospital referral, this was significantly more likely to have occurred. The commonest reason for a radiograph in patients with suspected lower respiratory tract infection is to confirm the infection. In the opinion of the general practitioner the results of the radiograph do affect patient treatment. The wording of the radiologists report is associated with patient management.
Following an outline that details the pathogens causing community-acquired pneumonia (CAP) identified in studies from Europe, this article reviews the guidelines for the management of CAP in four European countries--France, Italy, Spain, and the United Kingdom. The method behind the development of each document is described, followed by a comparison of the scope of each document. All four documents provide guidelines for the management of two groups of patients--the severely ill and the nonseverely ill patient. A penicillin or macrolide feature for the nonseverely ill and the combination of a third-generation cephalosporin plus a macrolide for the severely ill patient are described in all four guidelines. Despite their different origins and methods, these four guidelines have more similarities than differences--the latter serving to emphasize some of the areas that require further research in this important condition. An important area for research is the impact that these guidelines have on practice and especially on clinical outcomes.
Most patients with pneumonia never reach the hospital but are managed in the community. Unlike patients admitted to the hospital, in most, no investigations are performed and the diagnosis is based on clinical features. Less than half of those with clinical pneumonia have radiographic infiltrates and some of those with lower respiratory tract infection that is not considered to be pneumonia do. Few studies have investigated this condition, partly because of these diagnostic difficulties. The importance of distinction of these conditions is uncertain at present. The role of microbiological investigations in patients with pneumonia in the community requires clarification. For most patients it is unlikely that such tests will alter management, but it is not possible to predict those in whom such tests may help. What little is known about the microbial cause of pneumonia managed outside of the hospital is that the causative pathogens are similar to those found in studies of hospitalized patients, with the exception of pathogens usually associated with severe illness such as legionella and staphylococci, which are uncommon. Empirical antibiotic therapy can be predicted from the above findings, but much further research is required to fill in current gaps in our knowledge.
Previous attempts to extract high-quality, total RNA from raspberry (Rubus idaeus) fruits using published protocols have proven to be unsuccessful. Even the use of protocols developed for the extraction of RNA from other fruit tissue has resulted in low yields (1) or the isolation of degraded RNA (2). Here, we report on the development of a quick and simple method of extracting total RNA from raspberry fruit. Using this method, high yields of good quality, undegraded RNA were obtained from fruit at all stages of ripening. The RNA is of sufficient quality for northern analysis and cDNA library construction.
Extraction of high-quality RNA from blackcurrant fruit has hitherto proved difficult, probably owing to high levels of phenolic and polysaccharide components in the berries. The procedure described here is a modification of one described for grape berries, and yields RNA suitable for in vitro translations, RNA blot analysis, and cDNA library construction.
Lower respiratory tract infections (LRTIs) are one of the most frequent medical conditions seen in out-patients. They all cause morbidity, and although most are minor some may be life-threatening, thus appropriate disease management is important. Clinical features are usually used to classify LRTIs, but this approach may be inaccurate. It may therefore be simpler to describe a patient's symptoms without applying a label, such as "bronchitis", since the latter means different things to different people. Classification of LRTIs should aim to aid management. The two main management decisions are: whether to manage the patient at home; and whether to prescribe antibiotics. Investigations are carried out in the hospital environment to aid these decisions, however in the community investigation in only a minority of cases are done as they are costly and impractical. Markers of severity of LRTI have been identified in a number of studies and their value in clinical practice is now being assessed, however most studies suggest that severely ill patients are correctly identified and admitted to hospital. Currently, antibiotics are used liberally for lower respiratory tract infections. However most infections are not bacterial in origin and will not be affected by such therapy. The idea that antibiotics are harmless placebos for such illnesses is no longer tenable since the appearance and rapid spread of antibiotic resistance in bacteria. Only in community-acquired pneumonia and some patients with exacerbations of chronic bronchitis do antibiotics actually alter the course of the illness. In those groups antibiotics should be targetted at the casual pathogens and in other groups such therapy should be avoided. Much current research interest is focused on determining which (if any) is the best antibiotic in these situations.
BACKGROUND: The purpose of this study was to identify factors on which European general practitioners (GPs) base their decisions to admit to hospital patients with lower respiratory tract infections (LRTI). METHODS: A survey was carried out from December 1993 to January 1994 to identify factors that affect GPs' decisions to admit to hospital patients with LRTI by collecting data on 2056 patients from 605 GPs in France, Germany, Italy, Spain, and the UK. RESULTS: Only 93 (4.5%) of the patients included in the study were admitted to hospital. Univariate analysis showed that age > 60 years, institutionalisation of the patient, concomitant diseases, cardiac insufficiency, asthma, a diagnosis of pneumonia, and clinical signs such as chest pain, cyanosis, tachypnoea and hypotension significantly (odds ratio (OR) > 2.0, p < 0.002) influenced the decision to admit to hospital. No influence could be shown for sex, smoking habits, history of bronchiectasis or chronic bronchitis, the presence of fever, chills, myalgia, cough or purulent sputum, and the diagnoses of acute bronchitis, influenza or exacerbation of chronic bronchitis. In the multivariate analysis only the presence of chest pain (OR 2.3, 95% confidence interval (CI) 1.5 to 3.5), cyanosis (OR 4.1, 95% CI 2.4 to 7.1), dyspnoea (OR 4.9, 95% CI 3.1 to 7.9), and hypotension (OR 2.9, 95% CI 1.6 to 5.2), as well as a diagnosis of pneumonia (OR 6.6, 95% CI 4.3 to 10) (all p < 0.00001) remained as factors that significantly affected the decision to admit to hospital. CONCLUSIONS: Clinical signs of severe infection and a diagnosis of pneumonia are the main factors that induce GPs to admit patients with LRTI to hospital in Europe.
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A survey of first-line antibiotic prescription in community-acquired lower respiratory tract infection (LRTI) by general practitioners (GP) was carried out simultaneously, using the same methodology in France, Germany, Italy, Spain and the UK. Data were obtained from 2,056 patients and 605 GPs. There was no antibiotic prescription in 17% of all LRTIs and 13% of community-acquired pneumonia (CAP) in the five countries taken together; and in 32% of all LRTIs and in 23% of CAP in Germany. Of patients with acute bronchitis, exacerbation of chronic bronchitis and viral lower respiratory tract infection, 87, 92 and 71% received antibiotics, respectively. The most frequent prescriptions were penicillins in France and the UK, third-generation cephalosporin in Italy, tetracycline in Germany and macrolide in Spain. The daily dosage of aminopenicillin prescribed was: 41% <1.5 g; 49% > or = 1.5 g and <3 g; and 10% > or = 3 g. In Italy, 53% of all antibiotics were injected in all LRTIs, and 71% in CAP; in contrast, antibiotic injection was lower than 2% both in the UK and Germany, with an average of 14% in the five countries combined. We conclude that there are variations in antibiotic prescription by GPs in Western Europe; differences are likely to be multifactorial, but could, in part, be explained by differences in health systems and sources of information available to GPs.
A questionnaire survey was performed on the use of investigations and their impact on treatment of adult lower respiratory tract infection in the community. Data on the management of 2,056 such infections were obtained simultaneously from general practitioners in France, Germany, Italy, Spain and the UK. Diagnostic tests were only performed in 29% of cases. Chest radiographs were performed most frequently (22%), followed by peripheral blood white cell count (15%) and microbiological examination of sputum (7%), with major differences being found in the frequency of these tests both by clinical diagnosis and country. A change in initial antibiotic therapy was made in 12% of cases, with use of investigation being significantly linked to such changes. Second- and third-line antibiotics were significantly different to first-line therapy, with macrolides the most frequently prescribed second-line and quinolones the most frequently prescribed third-line antibiotics.
Although chemotherapy is considered the cornerstone of treatment for small cell lung cancer (SCLC), the majority of SCLC patients relapse and die of their disease within 2 years of diagnosis. Until newer, more effective drugs are developed, both optimization of available chemotherapeutic regimens and the use of combined chemotherapy/radiotherapy will be required to improve the survival of SCLC patients. Combining ifosfamide, carboplatin, and etoposide, among the most active single agents against SCLC, into the ICE regimen was a logical move that has resulted in improved response and survival rates. In limited and extensive SCLC, respectively, ICE and ICE administered with vincristine (VICE) have achieved overall response rates of 79% to 94% and 77% to 100% and 2-year survival rates of 24% to 33% and 9% to 25%, respectively. Treatment-related toxicities, especially myelosuppression, have hindered efforts to accelerate the administration of ICE and VICE regimens and to incorporate them into combined-modality treatments. However, the use of hematologic support measures, including growth factors and peripheral blood progenitor cells, may pave the way for maximizing the effectiveness of these regimens.
Guidelines for the management of lower respiratory tract infection have been published in four European countries. The scope of each of these articles is reviewed and the similarities, differences and deficiencies highlighted. Very little is known about how lower respiratory tract infections (LRTIs) are managed in routine practice in Europe, especially in the community. The available data suggest major differences in antibiotic use between countries which is likely to be multifactorial in origin.
However it is assessed, pneumonia is more important in the elderly than in any other age group. For community acquired or nosocomial pneumonia elderly adults far exceed any other age group with 97% of all pneumonia deaths occurring in this age group. Increasingly pneumonia in the immunocompromised elderly is also being seen. The factors which determine the increased frequency of pneumonia in the elderly include social effects, immune changes and physiological changes in the lungs. These are compounded by the effects of the high frequency of chronic disease in this group. The clinical presentation of pneumonia is slightly different in the elderly and this, together with the presence of underlying disease, may make diagnosis difficult; however, focal signs in the chest are nearly always present. Streptococcus pneumoniae is the most important cause of community acquired pneumonia in the elderly followed by Haemophilus influenzae and the influenza viruses. In contrast to younger adults Mycoplasma pneumoniae infection is rarely identified. The role of Gram-negative enterobacteria is unclear, with some studies suggesting that this is the most frequent pathogen, others finding no cases at all. The pathogens causing nosocomial pneumonia are similar to those in younger adults. Management is more difficult because of the effects of underlying diseases, altered drug pharmacokinetics and drug interactions and the outcome is significantly worse with 25% of adults with community acquired pneumonia dying in recent prospective studies.
Random ciliary orientation has recently been proposed as a variant of primary ciliary dyskinesia. We report a 12 year old boy with all the features of primary ciliary dyskinesia and absent nasal mucociliary clearance in whom repeated biopsies of the nasal epithelium showed normal ciliary beat frequency. The only abnormality discovered was disorientation of the central microtubules of his cilia.