Chlamydia pneumoniae and acute arterial thrombotic disease.
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Aged↗
Biomedical subjects
P J Cook
Publications and source records attributed to P J Cook.
Clinical aspects of Chlamydia pneumoniae infection.
This recently recognised member of the genus Chlamydia is one of the most widespread pathogens of man, though up to 90% of infected people have few or no symptoms. Several studies have estimated the population prevalence of antibodies to C. pneumoniae at 40-55% in the northern hemisphere, and over 60% in under-developed countries. The incidence of infections follows a cyclical pattern, with peaks at regular intervals of 2-10 years, but no apparent seasonal periodicity. Nosocomial transmission may be mediated by environmental surfaces as well as aerosols, and immunosuppression, for example by the human immunodeficiency virus, predisposes to infection. Chlamydia pneumoniae causes predominantly atypical pneumonia, often severe in adults, especially the elderly; including 5-10% of community-acquired pneumonia in Scandinavian countries. Serological evidence indicates associations with asthma, bronchitis, exacerbations of chronic airflow obstruction, otitis media and bronchiolitis. Several studies, using both serological and morbid anatomical techniques, also indicate associations with vascular atheroma and ischaemic heart disease, and with acute myocardial infarction. Chronic, latent and recurrent infections have been documented, and it is postulated that, like chronic or recurrent C. trachomatis infections, these may produce disease as a consequence of the host's immunological hypersensitivity. Several techniques are available for serological diagnosis: the technique of choice is micro-immunofluorescence, using fixed whole elementary or reticulate bodies as antigen, but antibody responses are highly variable. Traditional alternatives, antigen detection (by direct immunofluorescence or enzyme immunoassay) and cell culture, have major disadvantages. Polymerase chain reactions have not yet been widely applied to the clinical setting. tetracycline antibiotics, erythromycin and quinolones are not very efficacious in the treatment of C. pneumoniae infection. The azalide antibiotic, azithromycin, and the macrolide, clarithromycin, are active in vitro against C. pneumoniae, and may become treatments of choice. The development of anti-chlamydial vaccines remains an important research goal.
Adolescent↗
Concentrations of OPC-17116, a new fluoroquinolone antibacterial, in serum and lung compartments.
The efficacy of an antibiotic is usually predicted from serum concentration and MICs for likely pathogens, but in the lung, tissue concentrations may be more relevant. This study compares concentrations of a new fluoroquinolone, OPC-17116, in serum, epithelial lining fluid (ELF), alveolar macrophages and bronchial mucosa, in 24 adults. OPC-17116 400 mg was given daily for 4 days, and diagnostic bronchoscopy was performed up to 13 h after the final dose. Mucosal biopsies were taken from macroscopically normal sites, alveolar macrophages were harvested by lavage, and ELF volume was derived from urea concentrations in bronchial lavage fluid and blood. A microbiological assay, using Escherichia coli, was used to assay OPC-17116 concentration in serum, bronchial mucosa, ELF and alveolar macrophages. The mean concentration of OPC-17116 in serum was 1.2 mg/L. Serum concentrations were significantly exceeded in bronchial mucosa (mean ratio 3.13) in ELF (mean ratio 12.21) and in macrophages (mean ratio 194.52). Penetrations of these compartments considerably exceeded those reported for other fluoroquinolones, and concentrations in all tissues were substantially higher than previously reported MIC90 levels for a variety of bacteria, including Streptococcus pneumoniae. A clinical role for OPC-17116 is suggested in a wide range of respiratory infections, including those due to intracellular bacteria.
Adult↗
Chlamydia pneumoniae.
Chlamydia pneumoniae, a fairly recent addition to the genus Chlamydia, has been shown to cause community-acquired and nosocomial pneumonias, and to be a common infectious agent in human populations throughout the world. It has a wide variety of clinical presentations, and may be associated with ischaemic heart disease. Like other species in the genus, it is difficult to isolate by cell culture: clinical diagnosis therefore rests on other techniques, each of which presents particular problems. Those discussed in this review are cell culture, antigen detection by direct immunofluorescence and enzyme immunoassay, serological methods (exemplified by micro-immunofluorescence) and the polymerase chain reaction. Currently available treatments and the prospect of vaccination are also discussed.
Chlamydia Infections↗
Concentration of amoxycillin and clavulanate in lung compartments in adults without pulmonary infection.
BACKGROUND: The efficacy of an antibiotic is usually predicted from serum levels and MIC90 values for likely pathogens, but in the lung tissue concentrations may be more informative. This study compares concentrations of amoxycillin and clavulanate in serum, epithelial lining fluid (ELF), alveolar macrophages, and bronchial mucosa in 15 adults. METHODS: Amoxycillin 500 mg and clavulanic acid 250 mg were given 1-2 hours before diagnostic bronchoscopy for haemoptysis or radiological abnormality. Mucosal biopsy samples were taken from macroscopically normal sites, alveolar macrophages harvested by lavage, and ELF volume derived from urea concentrations in bronchial lavage fluid and blood. Amoxycillin was assayed by inhibition of growth of Micrococcus lutea, and clavulanate (in serum, ELF, and bronchial mucosa) by inhibition of growth of Klebsiella pneumoniae; in macrophages clavulanate was measured by high performance liquid chromatography. RESULTS: The median concentrations in serum were 6.90 mg/l for amoxycillin and 5.25 mg/l for clavulanate. The median bronchial mucosal concentration of amoxycillin was 2.99 mg/l and of clavulanate was 1.65 mg/l; the median concentrations in ELF were 0.89 and 0.96 mg/l, and in macrophages 0 and 0.76 mg/l, respectively. In macrophages amoxycillin levels were undetectable in 10 of 14 subjects (71%); by contrast, only 6 of 14 subjects (43%) had no detectable clavulanate. CONCLUSIONS: Clavulanate levels exceeded quoted MIC90 values (around 0.25 mg/l) for Legionella pneumophila both in ELF and in macrophages. Amoxycillin-clavulanate may therefore have a clinical role in infections with Legionella pneumophila.
Adult↗
Drinking and schooling.
We employ the National Longitudinal Survey of Youth data to explore the effect of youthful drinking on years of schooling and on the likelihood of college graduation. Our instruments for youthful drinking include the state beer tax and the minimum purchase age. Reduced form equations are also estimated. Our results indicate that heavy drinking in high school reduces the average number of years of schooling completed following high school. Other things equal, students who spend their high school years in states with relatively high taxes and minimum age are more likely to graduate from college.
Adolescent↗
Transcripts of individual Drosophila actin genes are differentially distributed during embryogenesis.
The temporal and spatial patterns of accumulation of transcripts from individual actin genes during Drosophila embryogenesis have been determined by in situ hybridization. We describe the subcloning into transcription vectors of unique DNA fragments derived from the 3' transcribed, but nontranslated region of each actin gene. These fragments then served as templates for the synthesis in vitro of single-stranded, radio-active gene-specific RNA probes. Probe characterization and hybridization to developmental RNA blots are presented, demonstrated the independent developmental accumulation of actin transcripts from each gene. Each gene-specific probe has been hybridized in situ to the transcripts present in embryonic frozen sections. The results of these experiments have demonstrated that transcripts from each actin gene accumulate differentially in developing Drosophila tissues. The 5C and 42A actin genes are cytoplasmic actin genes, with transcripts distributed in all cells and tissues of the developing embryo. Therefore these genes presumably encode the cytoplasmic actins used for functions common to all cells. Transcripts from both cytoplasmic actin genes are evenly distributed in preblastoderm embryos, becoming localized to the periphery at blastoderm formation [5C: Burn et al.: Dev Biol 131:345-355, 1989]. Later in development, levels of these cytoplasmic transcripts vary in specific tissues. While the patterns of localization of 5C actin transcripts have been published [Burn et al.: Dev Biol 131:345-355, 1989], differential neurological localization is presented here; 42A transcripts are localized at higher concentrations in the midgut, the brain, nerve cord, and gonad. Both 87E and 57B transcripts accumulated in the developing larval body wall musculature, but at differing levels and in differing patterns. Transcripts of the 79B and the 88F actin genes were undetectable in embryos. The results of these experiments suggest dedicated contributions of individual actin genes to complex developmental processes.
Actins↗
The cultural dimensions of alcohol policy worldwide.
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Alcoholism↗
Some polymorphisms in the Salones.
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Alleles↗
Polymorphisms in some racial groups in Burma.
Data are presented on serum and red cell polymorphisms in five ethnic groups in Burma, the Chin, Naga, Kachin, Shan and Kayah. Gene frequencies are discussed in relation to the present geographical locations of the groups and their probable history of migration.
Alleles↗
Benzodiazepine hypnotics in the elderly.
A review is presented of the changes that occur in the pharmacodynamics of benzodiazepines during normal ageing and as a result of disease. Controlled studies in which subjects of different ages have received single doses of diazepam, temazepam, nitrazepam and flunitrazepam have consistently shown an increase in the response to benzodiazepines in the elderly which is not explained by the effects of disease or by altered plasma concentrations. In general, healthy elderly subjects have a 2-3 fold greater response compared with the young. This change appears to be due to a change in the post-receptor mechanism of action. Cerebral diazepam concentrations are similar in young and elderly rats, though older animals also show an increased response and no consistent changes have been demonstrated in brain receptor binding. However, benzodiazepine-induced increases in GABA binding and GABA-induced increases in post-synaptic inhibition have been reported to be greater in aged animals. Regular daily dosing with most benzodiazepines leads to drug accumulation which is proportional to the elimination half-life. Regular dosing with diazepam, chlordiazepoxide, nitrazepam and flurazepam has also been found to produce more sedation in the elderly, particularly long stay patients who have a high incidence of dementia, and those with a low albumen or chronic renal failure. A controlled trial of 1 week's dosing with 5 mg of nitrazepam or 20 mg of temazepam in elderly in-patients showed that these doses produced significant impairment of psychomotor performance the morning after the last dose. Only about 50% of the patients were affected and many of these were frail patients with mild dementia on rehabilitation or long stay wards. The doses prescribed for these types of patients should not exceed 2.5 mg of nitrazepam or 10 mg temazepam.
Aged↗
Diazepam tolerance: effect of age, regular sedation, and alcohol.
The dose of intravenous diazepam required for sedation was estimated in a series of 78 patients aged 17-85 years given the drug for dental and endoscopic procedures. Multiple regression analysis showed a significant correlation (r = 0.71; p less than 0.001) between dose and age, body weight, the taking of regular sedation, and the taking of more than 40 g alcohol daily, but there were no differences in the doses required between men and women, smokers and non-smokers, inpatients and outpatients, or dental and endoscopy patients. Patients aged 80 required an average dose of 10 mg and patients aged 20 an average dose of 30 mg, and the dose required was much higher in those receiving regular sedation or having a high alcohol intake. Plasma total and free diazepam concentrations were measured in the second half of the series of patients (n = 37). Plasma concentrations required for sedation fell twofold to threefold between the ages of 20 and 80 and were significantly higher in those taking regular sedation or alcohol. Differences in the acute response to diazepam appeared to be due to differences in the sensitivity of the central nervous system (pharmacodynamic tolerance) rather than to differences in pharmacokinetic factors.
Adolescent↗
Hypnotic accumulation and hangover in elderly inpatients: a controlled double-blind study of temazepam and nitrazepam.
The hypnotic and residual sedative effects of the first and seventh of seven regular night-time doses of nitrazepam 5 mg, temazepam 20 mg, and placebo were studied in 58 elderly inpatients. Plasma temazepam and nitrazepam concentrations rose by about 50% and 113% respectively between the mornings of day 1 and day 7. Patients reported sleeping well more often after the first dose of either hypnotic (p less than 0.05), but there was no difference after the seventh dose. Reaction time was unchanged on the morning after the first dose but was significantly prolonged after the seventh dose of both hypnotics (p less than 0.01). The time taken to eliminate the letter E from a page of prose tended to be prolonged after the first dose of both drugs (temazepam v placebo, p less than 0.05; nitrazepam v placebo, not significant) and was further prolonged on the morning after the seventh dose of nitrazepam (nitrazepam v placebo, p less than 0.05). Thus plasma accumulation of the drug was associated with a deterioration in daytime performance. This change in performance did not correlate with age, cerebral blood flow, or plasma concentration, but patients of low intelligence tended to be more severely affected.
Aged↗
Alpha 1 antitrypsin deficiency: the clinical and physiological features of pulmonary emphysema in subjects homozygous for Pi type Z. A survey by the British Thoracic Association.
Hereditary deficiency of alpha 1 antitrypsin, the main serum inhibitor of proteolytic enzymes is associated with pulmonary emphysema of early onset. A multicentre survey of this disorder was started in 1976 and details of 166 subjects homozygous for the Z phenotype form the main body of this report. There were 126 index cases who were identified through chest clinics and 40 non-index cases who were identified through family studies. The index cases and many of the non-index cases had severe radiological and physiological abnormalities. A history of cigarette smoking had a significant effect upon the prognosis, but sex and occupational exposure to dust or fumes did not. There was a wide variance in lung function even among those who had never smoked.
Adult↗
Alpha 1 antitrypsin deficiency: clinical and physiological features in heterozygotes of Pi type SZ. A survey by the British Thoracic Association.
In a multicentre survey of alpha 1 antitrypsin deficiency 25 heterozygotes of type SZ were identified. Fourteen index cases were identified through chest clinics and 11 non-index cases through family studies. Emphysema was largely confined to index males who had smoked and there was little evidence of the disease among the non-index cases. It appears that the SZ phenotype may carry little or no extra risk of emphysema.
Adult↗
The effect of intravenous epoprostenol (prostacyclin, PGI2) on cerebral blood flow and cardiac output in man.
Epoprostenol (prostacyclin, PGI2) was given intravenously to seven healthy volunteers in a dose of 4 ng kg-1 min-1 over a 30 min period. Diastolic blood pressure fell but there was no change in cardiac output. The mean PGI2 concentration at the end of the infusion was 0.43 ng/ml (1.1 nM) and a significant inhibition of ADP-induced platelet aggregation occurred. Although obvious facial flushing occurred in all subjects and some subjects complained of headache, cerebral blood flow tended to fall. The results do not support the hypothesis that PGI2 acts as a physiological vasodilator involved in the homeostasis of normal cerebral blood flow.
Adolescent↗
Outcome of liver disease associated with alpha 1 antitrypsin deficiency (PiZ). Implications for genetic counselling and antenatal diagnosis.
We reviewed the hepatic features in 136 children with alpha 1 antitrypsin deficiency (PiZ). Eighty two were studied prospectively, 74 of whom had chronic liver disease. Sixty seven children with liver disease presented in the first four months of life, four were older infants and children with chronic liver disease, 10 (three with liver disease) were identified in studies of the family of these propositi, and one was identified when she had liver disease associated with infectious mononucleosis. By 17 years of age 20 of these 74 children with chronic liver disease had died, 20 had established cirrhosis, 19 had persisting liver disease, and only 15 had made a complete, clinical and biochemical recovery. The outcome of liver disease was similar in a further 39 previously unreported PiZ infants and children with liver disease who were not prospectively studied. Because liver disease affects only a proportion of infants with PiZ phenotype and because the severity of their liver disease is so variable, we have analysed the outcome of liver disease in 27 observed families and in 20 previously reported families with more than one child with PiZ. In 34 families the outcome of liver disease was similar in the two children. From an analysis of the families with a severely affected child, we conclude that if the first PiZ child of PiZ heterozygote parents has unresolved liver disease, there is a 78% chance that a second PiZ child will have similar liver disease. After careful counselling, fetoscopy, fetal blood sampling, and protease inhibitor phenotyping, possible termination of pregnancy should be carefully considered in these families.
Adolescent↗
Confirmation of linkage between antithrombin III and Duffy blood group and assignment of AT3 to 1q22 lead to q25.
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Antithrombin III↗