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PubMed2001

The methodological quality of randomized controlled trials of homeopathy, herbal medicines and acupuncture.

BACKGROUND: To investigate the methodological quality of randomized controlled trials in three areas of complementary medicine. METHODS: The methodological quality of 207 randomized trials collected for five previously published systematic reviews on homeopathy, herbal medicine (Hypericum for depression, Echinacea for common cold), and acupuncture (for asthma and chronic headache) was assessed using a validated scale (the Jadad scale) and single quality items. RESULTS: While the methodological quality of the trials was highly variable, the majority had important shortcomings in reporting and/or methodology. Major problems in most trials were the description of allocation concealment and the reporting of drop-outs and withdrawals. There were relevant differences in single quality components between the different complementary therapies: For example, acupuncture trials reported adequate allocation concealment less often (6% versus 32% of homeopathy and 26% of herb trials), and trials on herbal extracts had better summary scores (mean score 3.12 versus 2.33 for homeopathy and 2.19 for acupuncture trials). Larger trials published more recently in journals listed in Medline and in English language scored significantly higher than trials not meeting these criteria. CONCLUSION: Trials of complementary therapies often have relevant methodological weaknesses. The type of weaknesses varies considerably across interventions.

Acupuncture Therapy↗
PubMed2004

Antimicrobial prescribing patterns for respiratory diseases including tuberculosis in Russia: a possible role in drug resistance?

BACKGROUND: Inappropriate antibiotic prescribing exposes patients to the risk of side effects and encourages the development of drug resistance across antimicrobial groups used for respiratory infections including tuberculosis (TB). AIM: Determine among Russian general practitioners and specialists: (1) sources of antimicrobial prescribing information; (2) patterns of antimicrobial prescribing for common respiratory diseases and differences between primary and specialist physicians; (3) whether drug resistance in TB might be linked to over-prescribing of anti-TB drugs for respiratory conditions. METHODS: Point-prevalence cross-sectional survey involving all 28 primary care, general medicine and TB treatment institutions in Samara City, Russian Federation. In this two-stage study, a questionnaire was used to examine doctors' antimicrobial (including TB drugs) prescribing habits, sources of prescribing information, management of respiratory infections and a case scenario ('common cold'). This was followed by a case note review of actual prescribing for consecutive patients with respiratory diseases at three institutions. RESULTS: Initial questionnaires were completed by 81.3% (425/523) of physicians with 78.4% working in primary care. Most doctors used standard textbooks to guide their antimicrobial practice but 80% made extensive use of pharmaceutical company information. A minority of 1.7% would have inappropriately prescribed antibiotics for the case and 0.8-1.8% of respondents would have definitely prescribed TB drugs for non-TB conditions. Of the 495 respiratory cases, 25% of doctors prescribed an antibiotic for a simple upper respiratory tract infection and of 8 patients with a clinical diagnosis of TB, 4 received rifampicin monotherapy alone. Ciprofloxacin was widely but inappropriately used. CONCLUSION: Doctors rely on information provided by pharmaceutical companies; there was inappropriate antibiotic prescribing.

Anti-Bacterial Agents↗
PubMed2005

Trends in antibiotic prescribing for acute respiratory infection in veterans with spinal cord injury and disorder.

OBJECTIVES: Most acute respiratory infections (ARIs) are viral and do not warrant antibiotic therapy. Studies to date have not examined trends in antibiotic use in ARIs in populations with disabilities, thus we assessed antibiotic prescribing for veterans with spinal cord injury and disorder (SCI and D) with outpatient ARI visits. PATIENTS AND METHODS: Retrospective study using Department of Veterans Affairs (VA) administrative and pharmacy datasets (1 October 1998-30 September 2001; fiscal years 1999-2001) to assess antibiotic prescribing for upper respiratory infection (URI), lower respiratory infection (LRI), and pneumonia in veterans with SCI and D. RESULTS: There were 5713 ARI visits; 50% received new antibiotic prescriptions. URI and LRI visits were 2.3 times and almost 4 times (P < 0.0001), respectively, more likely to have antibiotics prescribed than pneumonia visits. The majority of URI visits with antibiotic prescriptions had a diagnosis of the common cold or URI not otherwise specified (78%). Acute bronchitis without exacerbation was associated with 95% of LRI visits that received antibiotics. Broad-spectrum antibiotic use increased over time (1999, 46%; 2001, 62%; P < 0.0001). CONCLUSIONS: Although rates of antibiotic prescribing remained stable, prescriptions for broad-spectrum antibiotics increased. Most prescriptions were for indications for which antibiotic use is generally not recommended. Since patients with SCI and D are susceptible to multiple complications, providers may be more concerned with ensuring that any infection is treated, rather than the potential for overuse and resistance. Future efforts should focus on defining benefits of antibiotic use for ARIs in those with disabilities, predictors of prescribing, and interventions to prevent injudicious use of antibiotics.

Acute Disease↗
PubMed1999

Scanning electron microscopy of human head louse (Anoplura: Pediculidae) egg and its clinical ramifications.

Pediculosis affects more elementary school students than all other communicable childhood diseases combined, excluding the common cold. The current study using scanning electron microscopy visualized operculums through which developing embryos received oxygen, as well as fracture lines within the adherent sheath by which the egg is attached to the hair. Using microscopic techniques, including freeze-fracturing, the mode of attachment of the sheath to the hair follicle was observed, in addition to the existence of several inner membranes enclosing the embryo within the egg structure. The chemical nature of the sheath is also analyzed using electron dispersive x-ray analysis.

Animals↗
PubMed2003

RNA cleaving '10-23' DNAzymes with enhanced stability and activity.

'10-23' DNAzymes can be used to cleave any target RNA in a sequence-specific manner. For applications in vivo, they have to be stabilised against nucleolytic attack by the introduction of modified nucleotides without obstructing cleavage activity. In this study, we optimise the design of a DNAzyme targeting the 5'-non-translated region of the human rhinovirus 14, a common cold virus, with regard to its kinetic properties and its stability against nucleases. We compare a large number of DNAzymes against the same target site that are stabilised by the use of a 3'-3'-inverted thymidine, phosphorothioate linkages, 2'-O-methyl RNA and locked nucleic acids, respectively. Both cleavage activity and nuclease stability were significantly enhanced by optimisation of arm length and content of modified nucleotides. Furthermore, we introduced modified nucleotides into the catalytic core to enhance stability against endonucleolytic degradation without abolishing catalytic activity. Our findings enabled us to establish a design for DNAzymes containing nucleotide modifications both in the binding arms and in the catalytic core, yielding a species with up to 10-fold enhanced activity and significantly elevated stability against nucleolytic cleavage. When transferring the design to a DNAzyme against a different target, only a slight modification was necessary to retain activity.

Binding Sites↗
PubMed1986

Childhood leukemia and infectious diseases in the first year of life: a register-based case-control study.

In the Netherlands, a nationwide register of children with leukemia formed the basis for a case-control study (1973-1980). Population controls were matched with the cases for the year of birth, sex, and place of residence at the time of diagnosis. The information was collected by mailed questionnaires addressed to the parents. The analyses concerned infectious diseases in the first year of life of children with acute lymphocytic leukemia and their controls. Common colds, periods of fever, and primary childhood infections showed relative risks (RR) of 0.8, 0.9, and 0.8, respectively, after adjustment for birth order, family size, social class, and residential space. Furthermore, fewer cases reported infectious diseases which required hospitalization in their first year of life (RR = 0.6, 95% confidence interval (CI) = 0.4-1.0). The general infection risk profile of children with acute lymphocytic leukemia is compatible with these findings: there were more first-born children among the patients (RR = 1.8; 95% CI = 1.1-2.7), more children from one-child families (RR = 1.4; 95% CI = 0.8-2.3), more children of parents with higher education (RR = 1.2; 95% CI = 0.9-1.5), and more rooms in patient's houses (RR = 1.4; 95% CI = 0.6-2.6).

Adolescent↗
PubMed1989

Antagonists of B2 bradykinin receptors.

Bradykinin and its active metabolites, produced by kallikreins at their sites of action, potently elicit a variety of biological effects: hypotension, bronchoconstriction, gut and uterine contraction, epithelial secretion in airway, gut, and exocrine glands, vascular permeability, pain, connective tissue proliferation, cytokine release, and eicosanoid formation. These effects are mediated by at least two broad classes of receptors. The most common is the B2 subtype. The availability of competitive antagonists of B2 receptors has provided powerful tools for the study of bradykinin's actions. The significance of kinins in certain human diseases is being explored by using these agents as potential therapeutic agents. Human clinical trials are under way to test the usefulness of bradykinin receptor antagonists to treat symptoms of the common cold and the pain associated with severe burns. Trials are also being comtemplated for use in treatment of asthma.

Airway Resistance↗
PubMed2002

Reducing agents inhibit rhinovirus-induced up-regulation of the rhinovirus receptor intercellular adhesion molecule-1 (ICAM-1) in respiratory epithelial cells.

Rhinoviruses are the major cause of common colds and of asthma exacerbations. Intercellular adhesion molecule-1 (ICAM-1) has a central role in airway inflammation and is the receptor for 90% of rhinoviruses. Rhinovirus infection of airway epithelium induces ICAM-1. Because redox state is directly implicated in inflammatory responses via molecular signaling mechanisms, here we studied the effects of reducing agents on rhinovirus-induced ICAM-1 expression, mRNA up-regulation, promoter activation, and nuclear factor activation. To investigate the effects of rhinovirus infection on the intracellular redox balance, we also studied whether rhinovirus infection triggers the production of reactive oxygen species. We found that reduced (GSH) but not oxidized (GSSG) glutathione (1-100 microM) inhibited in a dose-dependent manner rhinovirus-induced ICAM-1 up-regulation and mRNA induction in primary bronchial and A549 respiratory epithelial cells. GSH but not GSSG also inhibited rhinovirus-induced ICAM-1 promoter activation and rhinovirus-induced NF-kB activation. In parallel, we found that rhinovirus infection induced a rapid increase of intracellular superoxide anion that was maximal at the time of NF-kB activation. This oxidant generation was completely inhibited by GSH. We conclude that redox-mediated intracellular pathways represent an important target for the therapeutic control of rhinovirus-induced diseases.

Animals↗
PubMed2001

Doxylamine overdose as a potential cause of rhabdomyolysis.

Doxylamine succinate, an over-the-counter antihistamine, is commonly used as a nighttime sleep aid in the short-term management of insomnia. It is also used in combination with antitussive and decongestant agents for the temporary relief of common cold symptoms. Doxylamine is frequently involved in accidental and intentional overdoses. Rhabdomyolysis and secondary acute renal failure are rare but potentially serious complications, making early recognition and treatment essential. With the large number of nonprescription antihistamines and sleep aids available to the general public, it is important to keep in mind that overdose is a potential problem. The complications associated with overdose of these medications are just as life threatening as those associated with prescription drugs. A high index of suspicion and evaluation of rhabdomyolysis is warranted in antihistamine toxicity. We report an observation of severe rhabdomyolysis associated with doxylamine overdose.

Acute Kidney Injury↗
PubMed1993

Abuse of antibiotics in China and its potential interference in determining the etiology of pediatric bacterial diseases.

There is scant information about the etiology and epidemiology of bacterial diseases of infants and children in China because of very little success with bacterial culture. This study describes the severity of abuse of antibiotics among Chinese pediatricians and this abuse's potential interference in determining the etiology of bacterial diseases. According to a survey in Beijing Children's Hospital more than 98% of the patients in the Outpatient Department who were diagnosed with common cold were given antibiotics by physicians. More than one-third of the patients had been taking antibiotics before coming to the hospital. Using a sensitive Staphylococcus aureus assay we found that 70% of blood samples and 43% of cerebrospinal fluid samples from the patients with bacterial meningitis and pneumonia contained antibacterial activity. Bacteria were recovered significantly less often from the samples with antibacterial activity than from those who did not from which antibiotic was not recovered, both in blood (5.3% vs. 12.5%) and in cerebrospinal fluid (2.5% vs. 14.8%). This study indicates that antibiotic abuse is a severe problem in China and that judicious use of antibiotics is urgently needed.

Adolescent↗
PubMed2000

Judicious use of antibiotics for common pediatric respiratory infections.

BACKGROUND: Antibiotic resistance among common respiratory infection-producing bacteria such as Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis has become a major global public health problem. The use of antibiotics, whether or not medically justified for a particular illness, contributes to the development of resistant bacteria. To help to contain the proliferation of drug-resistant bacteria, members of the CDC and the American Academy of Pediatrics (AAP) recently published principles for the judicious use of antibiotics in common pediatric respiratory infections including the common cold, otitis media, sinusitis and tonsillopharyngitis. This article reviews the CDC/AAP principles for management of these illnesses and describes results of clinical practice studies in which efforts to improve the judicious use of antibiotics were undertaken. CONCLUSIONS: The success of the CDC/AAP principles in containing the increase in antimicrobial resistance depends upon their being practiced. Results of clinical practice studies indicate that judicious use of antimicrobial therapy in pediatric respiratory infections can be realized through education and persistence. More widespread educational and behavior modification efforts are necessary to reduce unnecessary prescription of antibiotics and to curtail the still burgeoning problem of bacterial resistance.

Acute Disease↗
PubMed1993

Abuse of over-the-counter dextromethorphan by teenagers.

Dextromethorphan, the d-isomer of the opiate agonist levorphanol, has none of the analgesic or sedative effects associated with the opiates and is approved for over-the-counter use as an antitussive. It is available, in various combinations with other medications, in nonprescription cough suppressant and common cold formulations, and its availability in the United States is not controlled. In this paper we have reported two cases of recreational use of dextromethorphan-containing cough syrup by two unrelated teenage boys. Despite the safety of this medication when used at the recommended dosage, there have been cases of "recreational" use of dextromethorphan as well as death by overdose. Although usually thought to be nonaddictive, dextromethorphan produces a substance dependence syndrome, and physicians should be aware of its abuse potential, particularly by youths.

Adolescent↗
PubMed1993

Extended follow-up in 212 long-term allogeneic bone marrow transplant survivors. Issues of quality of life.

A group of 235 allogeneic marrow recipients were contacted at least one year following their BMT to obtain information on their quality of life; 212 (90%) agreed to participate in this survey. A total of 162 adults and 50 pediatric survivors were interviewed during clinic visits (5%) or over the telephone (95%). Changes in productive activity and marital status at the time of interview were studied, as well as the presence of physical symptoms and perception of a general sense of well-being. Older transplant recipients were observed to have a significantly higher incidence of chronic graft-versus-host disease, common colds, and skin changes when compared with pediatric transplant recipients (P < 0.01). Older subjects were also more likely to require any type of regular medication. Younger survivors were rated with a higher Karnofsky performance status and global subjective score. There were no significant differences between patients who received TBI as part of the conditioning regimen and those who did not, with the exception of increased cataract development in pediatric patients receiving TBI (P < 0.008). We conclude that most allogeneic marrow transplant survivors, especially those individuals of younger age at the time of their transplants, are doing well in the domains tested.

Adolescent↗
PubMed2002

Management of acute bacterial rhinosinusitis.

Acute bacterial rhinosinusitis is an infection of the nasal epithelium and paranasal sinus mucosa, usually caused in children by Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, and, less frequently, group A Streptococcus species. The clinical diagnosis is based on daytime cough that may be worse at night or purulent rhinorrhea, or both, lasting at least 10 days, often worsening after a period of initial improvement after initial symptoms of the common cold, and often associated with facial or dental pain, facial fullness, or swelling, headache, and fever. Sinusitis is diagnosed clinically; radiographic evaluation is not indicated for diagnosis. When the disease persists despite treatment, or is complicated by potential intracranial or orbital extension, CT is the preferred imaging modality. Initial therapy should be amoxicillin in a high dosage (80-90 mg/kg/day). Treatment is generally for 10 to 14 days and for at least 7 days beyond the time of substantial improvement in symptoms. Complications of acute bacterial rhinosinusitis in children are rare.

Acute Disease↗
PubMed2001

Viral rhinitis and asthma.

Upper respiratory tract infections are among the most common infectious diseases. Approximately 80% of the common colds are caused by rhinoviruses. Recently, rhinovirus colds have been linked with lower airway illnesses such as asthma exacerbations resulting in a considerable interest in the pathogenesis of lower respiratory tract pathology. The important role that allergic airway disease plays in virally induced changes in airway function has been experimentally shown in several studies. Unfortunately, the precise mechanisms by which viruses could induce lower airway symptoms have not yet been determined.

Asthma↗
PubMed2004

Immune responses and the emergence of drug-resistant virus strains in vivo.

The treatment of viral infections using antiviral drugs has had a significant public health benefit in the setting of human immunodeficiency virus (HIV) infection, and newly developed drugs offer potential benefits in the management of other viral infections, including acute self-limiting infections such as influenza and picornaviruses (including the rhinoviruses that are responsible for a large proportion of 'common colds'). A serious concern with such treatments is that they may lead to the selection of drug-resistant strains. This has been a significant problem in the case of HIV infection. Existing mathematical-modelling studies of drug resistance have focused on the interactions between virus, target cells and infected cells, ignoring the impact of immune responses. Here, we present a model that explores the role of immune responses in the rise of drug-resistant mutants in vivo. We find that drug resistance is unlikely to be a problem if immune responses are maintained above a threshold level during therapy. Alternatively, if immune responses decline at a fast rate and fall below a threshold level during treatment (indicating impaired immunity), the rise of drug-resistant mutants is more likely. This indicates an important difference between HIV, which impairs immunity and for which immune responses have been observed to vanish during treatment, and viral infections such as influenza and rhinoviruses, for which such immune impairment is not present. Drug resistance is much more likely to be a problem in HIV than in acute and self-limiting infections.

Drug Resistance, Viral↗
PubMed1996

Th1 and Th2 cytokine induction in pulmonary T cells during infection with respiratory syncytial virus.

Helper T (Th) cells can be classified functionally into two main types. Broadly, Th1 cells play a major role in eliminating viral pathogens, while Th2 cells mediate anti-parasite immunity and allergic responses. These functions are thought to depend on characteristic and distinct patterns of cytokine production. Infection with human respiratory syncytial virus, an important common cold virus, causes transient lymphocytic bronchiolitis in mice. Activated T cells are partly responsible for this disease, but also eliminate the virus. To show whether polarized cytokine production occurs in individual cells during viral bronchiolitis, we sampled murine bronchoalveolar lavage and mediastinal lymph node cells before and after infection. RT-PCR of cellular mRNA and flow cytometric analysis of intracellular cytokine production showed a rapid IFN-gamma response at both sites, which persisted for more than 3 weeks in the lung. Most IFN-gamma-producing cells were CD8+. Some early CD4+ IFN-gamma-producing cells also made IL-10. Only low levels of IL-2, IL-4 and IL-5 mRNA or protein expression were detected at any time at either site. No cytokines were detected in B cell populations at either site. These novel techniques show the true complexity of cytokine production patterns on a cell-by-cell basis, allowing T cells to be reclassified according to function.

Animals↗
PubMed1996

Equine rhinovirus serotypes 1 and 2: relationship to each other and to aphthoviruses and cardioviruses.

Equine rhinoviruses (ERVs) are picornaviruses which cause a mild respiratory infection in horses. The illness resembles the common cold brought about by rhinoviruses in humans; however, the presence of a viraemia during ERV-1 infection, the occurrence of persistent infections and the physical properties are all more reminiscent of foot-and-mouth disease virus (FMDV). cDNA cloning and sequencing of the genomes of ERV-1 and ERV-2 between the poly(C) and poly(A) tracts showed that the serotypes are heterogeneous. Nevertheless, the genomic architecture of both serotypes is most similar to that of FMDV. Indeed, a comparison of the derived protein sequences of ERV-1 shows that their identity is greatest to FMDV. In contrast, most ERV-2 proteins are more related to encephalomyocarditis virus (EMCV) proteins than they are to FMDV or ERV-1. These results place ERV-1 alongside FMDV in the aphthovirus genus of the picornavirus family and indicate that this virus may serve as a model system for examining the biology of FMDV.

Amino Acid Sequence↗