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Epidemiology and significance of Q fever in the Federal Republic of Germany.

In the Federal Republic of Germany no large Q fever epidemics (more than 200 cases) have been encountered within the last 20 years; however, Q fever was prevalent throughout that period on a constant level (between 27 and 100 officially reported cases per year). Besides classical pneumonic Q fever, chronic forms associated with endocarditis, myocarditis and hepatitis were recently diagnosed for the first time in the Federal Republic of Germany. The disease Q fever in humans is often misdiagnosed as common cold or influenza, and more attention should be paid to this entity by the medical profession. Within ten years there has been a sharp increase of Q fever infections in livestock and pets as proved by seroepidemiologic investigations. Preliminary results of a seroepidemiological study indicate a parallel increase of seropositives in the human population, but further investigations on larger numbers of sera are required for statistic confirmation. There are reasons to believe that, in contrast to general opinion, in the Federal Republic of Germany C. burnetii is involved now in infertility in cattle, and besides being a zoonosis Q fever must be considered as a potentially important infectious disease of cattle causing economic losses in this country. Further investigations on this matter are required.

Animals↗

Validation of a HPLC quantification of acetaminophen, phenylephrine and chlorpheniramine in pharmaceutical formulations: capsules and sachets.

Acetaminophen, phenylephrine and chlorpheniramine are frequently associated in pharmaceutical formulations against the common cold. Their quantification presents several problems. A HPLC method for the simultaneous determination of these compounds in pharmaceutical formulations such as capsules and sachets, including the separation of impurities and excipients has been developed and validated. The selectivity of the method was also tested to be used if phenylpropanolamine hydrochloride were employed instead of phenylephrine. Final chromatographic conditions were a gradient elution, being solvent A: phosphate buffer 40 mM at pH 6.0 and solvent B: acetonitrile. At t=0, the mobile phase consisted of 92% A and 8% B and it changed with a linear gradient during 8 min to 75% A and 25% B. At min 8, it changed to 30% A and 70% B for 5 min and at t=15 min, it returns to the initial conditions (92% A and 8% B) during 1 min remaining at this composition until t=20 min. UV detection was performed at 215 nm for phenylephrine and chlorpheniramine, because at this wavelength sensitivity was higher than in other more characteristic wavelengths and it was necessary for the detection of minor compounds. For acetaminophen 280 nm was employed. Validation parameters permit to consider the method adequate.

Acetaminophen↗

Cross-cultural differences in lay attitudes and utilisation of antibiotics in a Belgian and a Dutch city.

Cultural differences are probably an important factor in the considerable variation in antibiotic use between countries. The objective of this study was to explore local cultural differences in the lay perspective on coping with URTD and using antibiotics. We interviewed 30 persons in a Dutch and a Belgian city. Twenty-one were interviewed a second time after 3 months. Between the first and second interview, they noted in a diary all URTD episodes experienced by themselves and their family members (N=69) and how they coped with them. The Dutch participants labelled most URTD episodes as "common cold" or "flu". The Flemish participants labelled most of their URTD episodes as "bronchitis" and used more antibiotics. Four categories of antibiotic users could be distinguished. Participants with a Protestant background were more sceptical about medicines than those with a Catholic background. A thorough understanding of the cultural context is necessary to design effective campaigns to promote rational antibiotic use.

Adult↗

[Community-acquired acute maxillary sinusitis or rhinosinusitis in adults in France: current management].

Sinus infections, often viral, are a common reason for physician visits. The multiplicity of clinical presentations makes its diagnosis difficult. The problem is to recognize bacterial infection without additional testing, except in cases of treatment failures, complications or relapse. Patients with signs suggestive of rhinosinusitis fall into one of four basic clinical situations: common colds, 'doubtful' rhinosinusitis, apparent acute maxillary bacterial rhinosinusitis, and complications. Anterior rhinoscopy may help confirm diagnosis. Current bacterial epidemiology is based on the results of clinical studies, microbial ecology, and samples taken in cases of treatment failure. The two bacteria isolated most frequently are Streptococcus pneumoniae and Haemophilus influenzae, both of which pose resistance problems. Moraxella catarrhalis, Streptococcus pyogenes and Staphylococcus aureus are isolated less often. The dominant issue in management of acute rhinosinusitis is whether to use antibiotic or symptomatic treatment. For viral infections, antibiotic therapy is useless and highly inadvisable. For 'doubtful' infections, symptomatic treatment is likely to lead to recovery. The use of non-recommended antibiotics also increases the risk of selection of resistant bacteria. When bacterial rhinosinusitis is strongly suspected, recourse to antibiotic treatment is recommended in view of the benefits in this situation (AFSSAPS 2005). This treatment is probabilistic, should be decided at the end of the consultation, and follows the AFSSAPS guidelines.

Anti-Bacterial Agents↗

A systematic review of the safety profile of levetiracetam: a new antiepileptic drug.

PURPOSE: This report provides detailed review of safety information on levetiracetam (LEV) (Keppra), a new antiepileptic drug. METHODS: The integrated summary of safety report submitted for regulatory review was examined to collate information about abnormal laboratory tests values and adverse event reports collected during the overall LEV development program. Analyses included 3347 patients exposed to LEV in clinical trials for epilepsy, cognition, and anxiety disorders. RESULTS: Safety data from all studies depict a similar pattern of adverse effects, predominantly somnolence, asthenia, and dizziness that occurred most frequently during the first month of LEV treatment. Changes in laboratory test values from placebo-controlled trials that were statistically significant remained in the normal range (red blood cells, hematocrit, hemoglobin, white blood cells, and neutrophils). Reports of the coding term 'infection' (common cold, upper respiratory infection) were not preceded by low neutrophil counts that might suggest impaired immunological status. Selection of adverse event coding terms probably contributed to the high rate of adverse effects termed 'infection.' Higher incidences of adverse effects, particularly behavioral effects, were found among epilepsy patients than in elderly patients with cognitive disorders or patients with anxiety disorders given lower doses. CONCLUSIONS: This review of patients evaluated during the clinical development program suggests that LEV was well tolerated and safe for patients with seizure, cognitive and anxiety disorders. Overall incidence of adverse effects in the LEV groups was little higher than reports from the placebo groups. Of course, this data was derived from clinical trials that are of relatively short duration, and provide data on only several thousand patients. Therefore, long-term side effects, and/or rare side effects cannot be ruled out on the basis of this analysis.

Anticonvulsants↗

Rational antibiotic use and academic staff.

This study was devised to determine the knowledge, attitude and behaviour of an educated group of people towards antibiotic use and self-medication with antibiotics. Of 1380 members of academic staff (excluding those from the Faculty of Medicine) of Ege University, 602 were chosen by systematic sampling methods. Two groups were formed. Group A included academic staff from the Faculties of Dentistry and Pharmacy and Group B, members of all other faculties. The mean age was 37.4+/-11.0 and 47.0% were females. The mean antibiotic knowledge score was 7.16+/-3.32. Self-medication with antibiotics was admitted by 45.8% of the total samle and 15.6% of the respondents used antibiotics until their symptoms disappeared regardless of the period of prescription. In Group A 48.8% and in Group B 80.7% of the respondents believed that antibiotics could be used for common cold. It is concluded that priority should be given to knowledge-based behaviour education programmes for the more highly educated community; there must also be restriction on the sale of antibiotics without prescription.

Adult↗

Inhibitory effect of andrographolide from Andrographis paniculata on PAF-induced platelet aggregation.

Andrographolide, an active principle of the Chinese drug Andrographis paniculata, used for prevention and treatment of common cold in Scandinavia and known as an antiinflammatory, antiviral, antithrombotic, hypotensive and antiatherosclerotic drug, was investigated for its suggested influence on the biosynthesis of eicosanoids and the platelet-activating factor (PAF). Whereas in isolated human polymorph-nuclear leukocytes (PMNL) no influence on the biosynthesis was found, it could be shown that andrographolide inhibits PAF-induced human blood platelet aggregation in a dose dependent manner (IC50-5 microM). These results indicate that andrographolide has a mechanism of action different from that of non-steroidal antiinflammatory drugs (NSAID) and most likely associated with the cardiovascular and antithrombotic activity described of Andrographis paniculata.

Adult↗

Human rhinovirus 3 at 3.0 A resolution.

BACKGROUND: The over 100 serotypes of human rhinoviruses (HRV) are major causative agents of the common cold in humans. These HRVs can be roughly divided into a major and minor group according to their cellular receptors. They can also be divided into two antiviral groups, A and B, based on their sensitivity to different capsid-binding antiviral compounds. The crystal structures of HRV14 and HRV16, major-receptor group rhinoviruses, as well as HRV1A, a minor-receptor group rhinovirus, were determined previously. Sequence comparisons had shown that HRV14 seemed to be an outlier among rhinoviruses. Furthermore, HRV14 was the only virus with no cellular 'pocket factor' in a hydrophobic pocket which is targeted by many capsid-binding antiviral compounds and is thought to regulate viral stability. HRV3, another major-receptor group virus, was chosen for study because it is one of a subset of serotypes that best represents the drug sensitivity of most rhinovirus serotypes. Both HRV3 and HRV14 belong to antiviral group A, while HRV16 and HRV1A belong to antiviral group B. RESULTS: HRV3 was found to be very similar to HRV14 in sequence and structure. Like HRV14, crystallized HRV3 also has no bound pocket factor. The structure of HRV3 complexed with an antiviral compound, WIN56291, was also determined and found to be similar to the same antiviral compound complexed with HRV14. CONCLUSIONS: The amino-acid sequence and structural similarity between HRV3 and HRV14 suggests that rhinoviruses in the same antiviral group have similar amino-acid sequences and structures. The similar amino-acid composition in the pocket region and the viral protein VP1 N termini in all known group B HRV sequences suggests that these viruses may all contain pocket factors and ordered N-terminal amphipathic helices in VP1. Both of these factors contribute to viral stability, which is consistent with the observations that group B rhinoviruses have a higher chance of successful transmission from one host to another and is a possible explanation for the observed higher pathogenicity of these rhinoviruses.

Antigens, Viral↗

Allergic rhinitis and ear pain in flight.

BACKGROUND: Ear pain is the most common physiologic incident in hypobaric chamber training in the Japan Air Self-Defense Force, and the incidence of ear pain has been gradually increasing. There has been a concomitant increase in the incidence of allergic rhinitis in Japan. We hypothesized that the increased incidence of ear pain may be due to the increased incidence of eustachian tube dysfunction associated with allergic rhinitis. OBJECTIVE: To explore whether there is an association between allergic rhinitis and ear pain experienced in hypobaric chamber training. METHODS: We examined 9 years of training records and noted whether there was a seasonal influence on the occurrence of ear pain in 7047 trainees. In addition, we studied the prevalence of allergic rhinitis among trainees during a representative training year using a questionnaire method, noting association between allergic rhinitis and the occurrence of ear pain. RESULTS: Comprehensive review of training records showed 429 (6.1%) of 7047 trainees complained of ear pain. Ear pain occurred more often in spring than the other 3 seasons. The questionnaire data showed 202 (23.0%) of 878 trainees had allergic rhinitis. Trainees with allergic rhinitis complained of ear pain more often in the spring than trainees without allergic rhinitis. CONCLUSIONS: Active allergic rhinitis is closely associated with the occurrence of ear pain in hypobaric chamber training. A similar phenomenon might occur in an actual flight. Special attention should be paid to not only common cold but also allergic rhinitis in both hypobaric chamber training and actual flights.

Aerospace Medicine↗

Use of herbal remedies by patients in a health maintenance organization.

OBJECTIVE: To examine the use of and experiences with herbal remedies among a group of patients enrolled in a health maintenance organization (HMO). DESIGN: Self-administered questionnaire. SETTING: Central Texas city. PARTICIPANTS: 135 HMO patients. INTERVENTION(S): Not applicable. MAIN OUTCOME MEASURE: Patients' self-reported use of herbal remedies. RESULTS: Almost 40% of patients indicated they had used herbal remedies. The majority had used herbal remedies to treat or prevent a health condition (e.g., common cold). The remedies most frequently used were garlic, aloe gel, cranberry, and echinacea. Most respondents gathered their information on herbal remedies from the popular media, and most based their use decisions primarily on the recommendations of friends and/or relatives. Although most were unsure of the quality of the products, they felt they were safe and somewhat effective, and few had experienced any direct side effects they attributed to the herbal remedies. Most patients used the products without the knowledge of their physician or pharmacist. Herbal remedies were most often used in place of prescription or over-the-counter (OTC) medications and most frequently purchased in health food stores and mass merchandizer/grocery stores. Herbal remedies were sometimes used along with prescription or OTC medications. CONCLUSION: Given that patients are using herbal remedies for a variety of health conditions without medical supervision, pharmacists need to actively and consistently obtain information about herbal remedy use to effectively advise patients and monitor outcomes. More research is needed on herbal remedy use among patient populations and on outcomes in patients who use herbal remedies to treat primary health conditions.

Adult↗

Respiratory infections and asthma: current treatment strategies.

Infections such as lower respiratory illness potentially contribute to the initiation of asthma and are major factors in recurring acute exacerbations of the condition. Although typical bacterial respiratory pathogens such as Streptococcus pyogenes, Streptococcus pneumoniae and Hemophilus influenzae do not initiate asthmatic exacerbations, data from a subgroup of adults suggest a potential role for Mycoplasma pneumoniae and Chlamydia pneumoniae in the onset of asthma. Common cold viruses, predominantly respiratory syncytial virus (RSV) in young children and rhinoviruses in older children and adults, are the major causes of acute exacerbations of asthma. These exacerbations are not prevented with maintenance therapies that are used for chronic asthma, but do respond to short courses of systemic corticosteroids. There are continued attempts to produce a successful vaccine and antiviral agents for the treatment of RSV that are more effective and more practical to use than ribavirin, which is currently the only available antiviral for RSV. The prevention and treatment of rhinovirus infections have focused on the major receptor for the virus, intercellular adhesion molecule-1 (ICAM-1), which is located on respiratory epithelial cells. A multivalent, recombinant, antibody fusion protein identified as CFY196 has high avidity for ICAM-1 and has the potential to protect against rhinovirus infection. Another approach for preventing and treating rhinovirus infection uses a recombinant, soluble, truncated form of ICAM-1 in which the transmembrane and intracellular domains of the protein have been deleted. An initial clinical study on this agent demonstrated clinical efficacy in ameliorating the symptoms of experimental rhinovirus infection in volunteers, but did not significantly prevent infection.

Acute Disease↗

Poly(ethyleneglycol) column for the determination of acetaminophen, phenylephrine and chlorpheniramine in pharmaceutical formulations.

New polar reversed-phase stationary phases in HPLC provide specific selectivities which can help to solve traditional chromatographic problems related to the development of chromatographic methods with widely different retention times for the sample components. One such case is the analysis of pharmaceutical formulations against the common cold. Acetaminophen, phenylephrine and chlorpheniramine, compounds with different polarities, are frequently associated in these drugs. An isocratic and rapid HPLC method for the simultaneous determination of the three compounds, acetaminophen, phenylephrine and chlorpheniramine, in capsules as pharmaceutical formulations, including the separation of impurities (4-aminophenol and 4-chloracetanilide) and excipients, has been developed and validated. The final chromatographic conditions employed a Supelco Discovery HS PEG column poly(ethyleneglycol) 15x0.46 cm, 5 microm. The mobile phase was 20 mM phosphate buffer, pH 7.0-acetonitrile (90:10, v/v) at a flow-rate of 1 ml/min. UV detection was performed at 215 nm for all the compounds except acetaminophen, which was measured at 310 nm. Validation parameters permit us to consider this method suitable.

Acetaminophen↗

Aetiological evaluation of foreign bodies in the ear and nose.

A clinical study has revealed that irritation caused by pre-existing diseases of the ear (e.g. chronic otitis externa, wax with chronic otitis externa, C.S.O.M. with otitis externa or the presence of wax in the meatus) and by those of the nose (e.g. acute or chronic rhinitis, chronic vestibulitis or the presence of dried, thick sticky mucus in the vestibule of the nose in the resolving stage of a common cold) are the major aetiological factor in foreign bodies in the ear and nose. Boredom, curiosity, whims to explore the natural cavities of the body, habit, acts of imitation, fun-making and mental retardation are only minor aetiological factors.

Boredom↗

Epidemiological studies on leptospirosis in Chiang Mai (Thailand).

A total of 270 serum samples collected in Chiang Mai province were examined for antibodies against leptospira using the microscopic agglutination test (MAT). Four of 40 serum specimens from patients who visited the hospital with the common cold, were positive with a titre of 20. Twelve (10.4%) of the 115 samples in the Doi Saket district showed a positive reaction. Only 2 of 115 sera of school children in Chiang Mai city had antibodies. Specific serovars detected were Leptospira hebdomadis (5), L. australis (3), L. icterohaemorrhagiae (2), L. bataviae (2), and one each of L. canicola, L. javanica and L. pyrogenes. One case of mixed infection with L. hebdomadis and L. javanica, and L. autumnalis and L. australis were observed.

Adolescent↗

Synergistic antioxidative effects of alkamides, caffeic acid derivatives, and polysaccharide fractions from Echinacea purpurea on in vitro oxidation of human low-density lipoproteins.

Preparations of Echinacea are widely used as alternative remedies to prevent the common cold and infections in the upper respiratory tract. After extraction, fractionation, and isolation, the antioxidant activity of three extracts, one alkamide fraction, four polysaccharide-containing fractions, and three caffeic acid derivatives from Echinacea purpurea root was evaluated by measuring their inhibition of in vitro Cu(II)-catalyzed oxidation of human low-density lipoprotein (LDL). The antioxidant activities of the isolated caffeic acid derivatives were compared to those of echinacoside, caffeic acid, and rosmarinic acid for reference. The order of antioxidant activity of the tested substances was cichoric acid > echinacoside > or = derivative II > or = caffeic acid > or = rosmarinic acid > derivative I. Among the extracts the 80% aqueous ethanolic extract exhibited a 10 times longer lag phase prolongation (LPP) than the 50% ethanolic extract, which in turn exhibited a longer LPP than the water extract. Following ion-exchange chromatography of the water extract, the majority of its antioxidant activity was found in the latest eluted fraction (H2O-acidic 3). The antioxidant activity of the tested Echinacea extracts, fractions, and isolated compounds was dose dependent. Synergistic antioxidant effects of Echinacea constituents were found when cichoric acid (major caffeic acid derivative in E. purpurea) or echinacoside (major caffeic acid derivative in Echinacea pallida and Echinacea angustifolia) were combined with a natural mixture of alkamides and/or a water extract containing the high molecular weight compounds. This contributes to the hypothesis that the physiologically beneficial effects of Echinacea are exerted by the multitude of constituents present in the preparations.

Amides↗

Synthesis and evaluation of peptidyl Michael acceptors that inactivate human rhinovirus 3C protease and inhibit virus replication.

Human rhinovirus, the chief cause of the common cold, contains a positive-sense strand of RNA which is translated into a large polyprotein in infected cells. Cleavage of the latter to produce the mature viral proteins required for replication is catalyzed in large part by a virally encoded cysteine proteinase (3Cpro) which is highly selective for -Q approximately GP- cleavage sites. We synthesized peptidyl derivatives of vinylogous glutamine or methionine sulfone esters (e.g., Boc-Val-Leu-Phe-vGln-OR: R = Me, 1; R = Et, 2) and evaluated them as inhibitors of HRV-14 3C protease (3Cpro). Compounds 1 and 2 and several related tetra- and pentapeptide analogues rapidly inactivated 3Cpro with submicromolar IC50 values. Electrospray mass spectrometry confirmed the expected 1:1 stoichiometry of 3Cpro inactivation by 1, 2, and several other analogues. Compound 2 also proved to be useful for active site titration of 3Cpro, which has not been possible heretofore because of the lack of a suitable reagent. In contrast to 1, 2, and congeners, peptidyl Michael acceptors lacking a P4 residue have greatly reduced or negligible activity against 3Cpro, consistent with previously established structure-activity relationships for 3Cpro substrates. Hydrolysis of the P1 vinylogous glutamine ester to a carboxylic acid also decreased inhibitory activity considerably, consistent with the decreased reactivity of acrylic acids vs acrylic esters as Michael acceptors. Incorporating a vinylogous methionine sulfone ester in place of the corresponding glutamine derivative in 1 also reduced activity substantially. Compounds 1 and 2 and several of their analogues inhibited HRV replication in cell culture by 50% at low micromolar concentrations while showing little or no evidence of cytotoxicity at 10-fold higher concentrations. Peptidyl Michael acceptors and their analogues may prove useful as therapeutic agents for pathologies involving cysteine proteinase enzymes.

3C Viral Proteases↗

Epidemiology of poisoning due to pharmaceutical products, Poison Control Centre, Seville, Spain.

A retrospective study of telephone calls concerning poisoning due to pharmaceutical products, attended by the Toxicological Information Service in Seville (Spain), is presented. The years 1993 and 1994 were analized. Demographic data including the age and sex of the patient, route of exposure, cause, type of poisoning and the therapeutic group, was obtained. The great majority were cases of acute poisoning due to domestic accident, attempted suicide took second place. Ingestion was the principal route of entry, and more males than females were affected. 35.2% were children under two. In general, the medicines most frequently involved were those affecting the nervous system (28.1%)--principally analgesics, anxiolytics and antidepressants--followed by dermatological agents (13.7%)--such as antiseptics and disinfectants-and those affecting the respiratory (medicines to treat common cold, bronchodilators, antitussives) and digestive systems (laxatives, antiacids). It is hoped that with knowledge of data from as many poisons centres as possible, an improvement may gradually be seen in the prevention of the such poisoning in the future.

Adolescent↗

Associations between infections and fatigue in a Dutch working population: results of the Maastricht Cohort Study on Fatigue at Work.

The relationship between fatigue and common infections was further explored, as part of a 3 year prospective cohort study on Fatigue at Work. The current study is based on seven successive questionnaires, covering the first 2 years of follow-up. The overall response at baseline was 45% (n = 12,140). On T1 10,592 (87.2% compared to baseline response) employees returned the questionnaire. For T2, T3, T4, T5 and T6, 10,270 (84.6%), 9655 (79.5%), 8956 (73.8%), 8692 (71.6%) and 8070 (66.5%) employees respectively returned the questionnaire. Self-administered questionnaires were used to determine the level of fatigue with the Checklist Individual Strength (CIS) and the occurrence of common cold, flu-like illness and gastroenteritis. Regression analysis using generalized estimated equations (GEE) were used for data analysis. We found a cross-sectional relationship between fatigue and the infections flu-like illness and gastroenteritis, and a longitudinal relationship between an infection as a predictor of fatigue. For fatigue as a predictor of an infection, we found odds ratios (ORs) of 1.35 (confidence interval (CI) 1.28-1.42) for flu-like illness and 1.33 (CI: 1.25-1.42) for gastroenteritis. The highest incidence of infections was found among employees who reported high fatigue levels on two successive occasions. The increased incidence of infections, is regarded as a substantial effect of fatigue because it is associated with significant absenteeism from work and leads to discomfort.

Chi-Square Distribution↗