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PubMed1987

Prophylaxis and treatment of rhinovirus colds with zinc gluconate lozenges.

Following a tolerance study, double-blind placebo controlled trials were conducted to determine the prophylactic effect of zinc gluconate lozenges on rhinovirus challenge and, in a third study, their therapeutic efficacy when given at the start of colds caused by virus inoculation was tested. In the prophylaxis study a total of 57 volunteers received lozenges of either zinc gluconate (23 mg) (29 volunteers) or matched placebo (28 volunteers) every 2 h while awake during a period of four and a half days. They were challenged with 10(2) tissue culture infecting dose (TCID50) of human rhinovirus 2 (HRV-2) on the second day of medication, and were monitored daily for symptoms and signs of colds and laboratory evidence of infection. Zinc reduced the total mean clinical score from 8.2 in the placebo group to 5.7 and the reduction of the mean clinical score was statistically significant on the second day after virus challenge. In the therapeutic study 69 volunteers were inoculated with 10(2) TCID50 of HRV-2 and those who developed cold symptoms were randomly allocated to receive either zinc gluconate lozenges (six volunteers) or matched placebo lozenges (six volunteers) every two hours they were awake for six days. Treatment of colds with zinc reduced the mean daily clinical score and this was statistically significant on the fourth and fifth day of medication. Similarly, medication also reduced the mean daily nasal secretion weight and total tissue count and these reductions were statistically significant on days two and six for nasal secretion weights and days four to six of medication for tissue counts when compared with placebo.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1988

Low-temperature stability of viruses in sludges.

Enteroviruses survived for up to 38 days without diminishing in numbers in extended-aeration sludges maintained at 5 degrees C. In oxidation ditch sludges similarly maintained, enteroviruses survived for up to 17 days without diminishing in numbers. The pHs of the sludges in this study were well inside the pH 6 to 8 corridor in which destruction of enteroviruses by the detergents and ammonia present in sludges reportedly does not occur. Unexplained, however, was the survival of large numbers of enteroviruses in sludges at pH 3.5, a pH at which some anionic detergents commonly present in sewage are rapidly virucidal. The long survival of enteroviruses in these sludges at 5 degrees C indicates that such sludges can probably be stored under refrigeration in the laboratory for extended periods while awaiting processing without suffering significant losses in enterovirus numbers.

Cold Temperature↗

PubMed1999

Antibiotic prescribing by pediatricians for respiratory tract infection in children.

To examine antimicrobial prescribing rates for viral respiratory tract infections by primary care pediatricians in the greater Toronto area, charts were reviewed for the week of 17-21 February 1997 at 61 pediatricians' offices. Antibiotics were considered appropriate if the diagnosis was compatible with bacterial infection. A total of 3,585 patient visits were reviewed. The common cold was the most common respiratory tract syndrome leading to an office visit (1,317 visits). The overall rate of appropriate antibiotic prescribing was 89.5%. There was no significant difference in prescribing when physicians were compared by year of graduation from medical school, sex, or location of training. Diagnostic codes (ICD-9 [International Classification of Diseases, 9th edition] codes) did not match the chart diagnosis in 41% of cases. Toronto primary care pediatricians appear to have a lower rate of inappropriate antibiotic prescribing than do primary care physicians in other regions of Canada and the United States.

Anti-Bacterial Agents↗

PubMed1980

Quantification of plasminogen activator activity associated with herpesvirus-transformed cells.

Herpesvirus-transformed cell lines were examined for plasminogen activator (PA) activity using a quantitative assay. Previous results of cold fibrin overlay assays indicated that herpesvirus-transformed hamster cell lines produce fibrinolytic activity. Quantification of this activity involved the use of an 125I-fibrin lysis assay in which medium previously incubated with transformed or normal cells was tested for its ability to lyse 125I-fibrin polymers. This assay indicated an enhanced production of plasminogen-dependent fibrinolytic activity by transformed hamster cells compared to hamster embryo fibroblasts. The kinetics of secretion failed to reveal a significant difference in plasminogen activator activity in cells transformed by either herpes simplex virus types 1 or 2 (HSV-1 or HSV-2); however, transformed cells exhibited a significant increase in activity over non-transformed cells. Further characterization of PA activity associated with cells transformed by HSV-1 or HSV-2 has revealed that the protease is secreted and can function extracellularly. Extracellular PA activity produced by HSV-transformed cells is detected more efficiently than the cell-associated enzyme. Extracellular PA can be induced in two different species of cells by infection with partially inactivated HSV-2. Lytic infection of human embryo lung cells by HSV-2 strain 333 did not enhance activity, but infection of these cells with virus inactivated by u.v. irradiation resulted in increased PA levels from the cells. Increased enzyme levels were also detected in hamster embryo fibroblasts infected with partially inactivated virus. Further investigation of this enzyme function may determine whether increased levels of protease will indicate oncogenic transformation in vitro by herpesviruses.

Animals↗

PubMed2000

Neuroinvasion by human respiratory coronaviruses.

Human coronaviruses (HCoV) cause common colds but can also infect neural cell cultures. To provide definitive experimental evidence for the neurotropism and neuroinvasion of HCoV and its possible association with multiple sclerosis (MS), we have performed an extensive search and characterization of HCoV RNA in a large panel of human brain autopsy samples. Very stringent reverse transcription-PCR with two primer pairs for both viral strains (229E and OC43), combined with Southern hybridization, was performed on samples from 90 coded donors with various neurological diseases (39 with MS and 26 with other neurological diseases) or normal controls (25 patients). We report that 44% (40 of 90) of donors were positive for 229E and that 23% (21 of 90) were positive for OC43. A statistically significant higher prevalence of OC43 in MS patients (35.9%; 14 of 39) than in controls (13.7%; 7 of 51) was observed. Sequencing of nucleocapsid protein (N) gene amplicons revealed point mutations in OC43, some consistently found in three MS patient brains and one normal control but never observed in laboratory viruses. In situ hybridization confirmed the presence of viral RNA in brain parenchyma, outside blood vessels. The presence of HCoV in human brains is consistent with neuroinvasion by these respiratory pathogens. Further studies are needed to distinguish between opportunistic and disease-associated viral presence in human brains.

Brain↗

PubMed1996

Incubation periods of experimental rhinovirus infection and illness.

Eleven young adults with experimental rhinovirus infection (cases) and six noninfected saline-challenged young adults (controls) underwent nasal washings and symptom evaluations at 2-hour intervals for 24 hours after intranasal challenge. The mean and median periods to the first recovery of virus were 11.3 hours and 10 hours, respectively. Geometric mean rhinovirus titers in cases reached 10(0.2) log10 TCID50 (50% tissue culture infective dose)/0.1 mL at 10 hours and rose to 10(1.0) log10 TCID50/0.1 mL at 18 hours. Nine (82%) of 11 cases and one (16.7%) of six controls had colds. Mean total symptom scores for cases became significantly higher than those for controls at 16 hours. Sore or scratchy throat appeared between 10 and 12 hours in cases, but nasal obstruction and rhinorrhea first appeared at 2 hours, thus suggesting some nasal irritation from the viral inoculum pool. The incubation period of experimental rhinovirus infection is similar to that in cell culture. Nasal and pharyngeal symptoms began early in infection.

Adult↗

PubMed1983

Efficacy and tolerance of intranasally applied recombinant leukocyte A interferon in normal volunteers.

The prophylactic effect of recombinant leukocyte A interferon (rIFN-alpha A) (dosage, 10 X 10(6) units per day for four days) against illness and infection in 26 volunteers challenged with rhinovirus type 13 was measured in a double-blind, placebo-controlled study. Significant reductions in illness frequency (7.1% vs 66.7%, P less than 0.003), mean symptom scores, nasal secretion weights, and frequency of virus isolation were observed. However, there was no significant difference in infection rates between rIFN-alpha A- and placebo-treated volunteers. Late posttreatment virus shedding, which was unassociated with late illness, was observed in the rIFN-alpha A-treated group. In two double-blind, placebo-controlled tolerance studies of rIFN-alpha A, five (26%) of the 19 volunteers treated with rIFN-alpha A reported bleeding mixed with mucous nasal discharge and had documented superficial erosions of the nasal mucosa. Future studies will be necessary to evaluate lower doses and/or alternative treatment schedules for improved tolerance and continued efficacy.

Administration, Intranasal↗

PubMed2005

The role of rhinovirus in asthma exacerbations.

Rhinoviruses are a major cause of asthma exacerbations in children and adults. With the use of sensitive RT-PCR methods, respiratory viruses are found in approximately 80% of wheezing episodes in children and in approximately one half of such episodes in adults. Rhinovirus is a member of the family Picornaviridae, and acute rhinovirus infections occur predominantly in the upper airway. This virus has also been identified in the lower airway, and it might cause acute wheezing through the production of proinflammatory mediators with a resulting neutrophilic inflammatory response. Precisely how this process leads to increases in airway hyperresponsiveness and airway obstruction is not fully established. However, risk factors for wheezing with colds include asthma and atopy, extremes in age, and perhaps having a deficient TH1 response to rhinovirus. With the use of in vitro models and experimental inoculation studies, significant advances have led to a better understanding of the mechanisms by which rhinovirus infections cause asthma exacerbations. Advances in our understanding of this interaction might provide knowledge that could ultimately lead to specific treatment modalities to prevent and/or treat this significant burden of asthma exacerbations.

Adult↗

PubMed2003

Misconceptions about colds and predictors of health service utilization.

OBJECTIVE: Colds accounted for 1.6 million emergency department (ED) visits and 25 million ambulatory visits by children and adults in 1998. Although most colds are caused by viruses and do not require medical intervention, many families seek health care for the treatment of colds. Parental misconceptions about the cause and appropriate treatment of colds may contribute to unnecessary health service utilization. The objective of this study was to determine predictors of reported ED use and ambulatory care use for colds among families with young children. METHODS: This study was an observational, prospective cohort study to determine attack rates for respiratory illnesses within families that have at least 1 child who is 6 months to 5 years of age and enrolled in out-of-home child care. Families were randomly selected from 5 pediatric practices in Massachusetts and were considered eligible when the child was enrolled in child care with at least 5 other children for >or=10 hours per week. Enrolled families were asked to complete a survey that assessed knowledge about colds, antibiotic indications, and frequency of health service utilization. Predictors of self-reported use of health care services were assessed in multivariate logistic regression models. RESULTS: Of the 261 families enrolled in the study, 197 families (75%) returned completed surveys. Although 93% of parents understood that viruses caused colds, 66% of parents also believed that colds were caused by bacteria. Fifty-three percent believed that antibiotics were needed to treat colds. Parents reported that they would visit the ED (23%) or their doctor's office (60%) when their child had a cold. Predictors of ED use on multivariate analysis included Medicaid insurance (odds ratio [OR]: 17.6 [2.2-139.3]), history of wheezing (OR: 18.3 [4.4-75.8]), and belief that antibiotics treat colds (OR: 4.2 [1.4-12.9]). Predictors of ambulatory care use included parent younger than 30 years (OR: 10.0 [1.6-64.3]), history of wheezing (OR: 5.6 [1.1-29.7]), and belief that antibiotics treat colds (OR: 3.8 [1.7-8.5]). CONCLUSIONS: Misconceptions about the appropriate treatment of colds are predictive of increased health service utilization. Targeted educational interventions for families may reduce inappropriate antibiotic-seeking behavior and unnecessary health service utilization for colds.

Adult↗

PubMed1987

Failure of intranasally administered 4', 6-dichloroflavan to protect against rhinovirus infection in man.

4',6-Dichloroflavan, a potent inhibitor of rhinovirus replication in tissue culture systems was tested in a double-blind, placebo-controlled volunteer trial for its protective efficacy against experimental rhinovirus infection. Dichloroflavan was administered intranasally as a 5 per cent w/v aqueous suspension (40 mg; 5 times per day) for 5 doses before and 21 doses after intranasal challenge with rhinovirus type 9, a virus type known to be highly sensitive to the drug when tested in tissue culture. A total of 49 volunteers were included in the efficacy analysis. Dichloroflavan did not produce any consistent or significant reduction in clinical or laboratory parameters of infection. Indeed there was some indication that treatment with the drug may have been associated with increased severity of clinical signs and symptoms. Dichloroflavan administered intranasally is not, therefore, of value in the prevention of human rhinovirus infection.

Administration, Intranasal↗

PubMed1991

An approach to pediatric upper respiratory infections.

Upper respiratory tract infections are the most common diseases encountered in office pediatrics. The majority of these illnesses, including the common cold and pharyngitis, are viral in etiology, present with rhinitis and fever, and are self-limited and benign. Management consists of fluids, rest, saltwater nose drops and analgesics. Antihistamines appear to relieve only those symptoms potentiated by allergy. With the exception of streptococcal pharyngitis, upper respiratory tract infections do not require antibiotic therapy. However, otitis media and sinusitis, which sometimes are difficult to diagnose, are markedly improved by antibiotics that cover Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis. In 10 percent of children, otitis media and sinusitis are recalcitrant to antibiotic therapy. For these patients, referral to an otolaryngologist, myringotomy, placement of tympanostomy tubes or a short trial of prednisone may be efficacious.

Analgesics↗

PubMed1974

Are recommended daily allowances for vitamin C adequate?

The Recommended Dietary Allowance of vitamin C (ascorbic acid) for adults has now been set at 45 mg day(-1) by the U.S. Food and Nutrition Board. This intake suffices to prevent scurvy in most people. It is, however, much less than the optimum intake, the intake that leads to the best of health. A larger intake decreases the incidence and severity of the common cold and other diseases. Ascorbic acid has antiviral and antibacterial activity and is required for phagocytic activity of leukocytes. Several arguments indicate that for different human beings the optimum intake lies between 250 mg day(-1) and a much higher value, 5000 mg day(-1) or more. It is proposed that the present Recommended Dietary Allowance of 45 mg day(-1) of vitamin C for adults be renamed the Minimum Dietary Allowance, defined as the amount needed to prevent scurvy, and that, after consideration of the evidence about intake and the best of health, there be formulated another category of values, the Recommended Daily Intake, with the suggested range of 250 mg day(-1) to 4000 mg day(-1) of ascorbic acid for an adult.

Ascorbic Acid↗

PubMed1982

Panel discussion: pathogenesis of otitis media. Bacteriology and immunology.

Three features of otitis media with effusion (OME) are important in understanding its pathogenesis: 1. it is most common among children, when the eustachian tube is poorly developed; 2. it is most common during the winter months, when the common cold is prevalent; and 3. bacteria are found in a large number of middle ear effusions from OME patients. Although middle ear effusions are conventionally thought to be sterile, numerous recent investigations favor a bacterial pathogenesis of OME. Four possibilities can be considered: 1. bacteria are modified by antibiotics or antibodies, causing a lingering inflammation; 2. early antibiotic treatment may interfere with the development of local immunity; 3. bacterial antigen trapped in the middle ear causes immune injury leading to OME; and 4. bacterial endotoxin and inflammatory mediators cause middle ear effusions.

Animals↗

PubMed1998

Comparison of immunofluorescence with monoclonal antibodies and RT-PCR for the detection of human coronaviruses 229E and OC43 in cell culture.

Human coronaviruses, with two known serogroups named 229E and OC43, cause up to one third of common colds and may be associated with serious diseases such as nosocomial respiratory infections, enterocolitis, pericarditis and neurological disorders. Reliable methods of detection in clinical samples are needed for a better understanding of their role in pathology. As a first step in the design of such diagnostic procedures, the sensitivities and specificities of two viral diagnostic assays were compared in an experimental cell culture model: an indirect immuno-fluorescence assay using monoclonal antibodies and reverse transcriptase-polymerase chain reaction amplification of viral RNA from infected cells. Immunofluorescence detected human coronaviruses in cells infected at a MOI as low as 10(-2) (log TCID50/ml = 4.25 for HCV-229E and 2.0 for HCV-OC43; log PFU/ml = 4.83 for HCV-229E and 1.84 for HCV-OC43) versus 10(-3) (HCV-OC43) or 10(-4) (HCV-229E) for reverse transcriptase-polymerase chain reaction amplification (log TCID50/ml = 1.75 for HCV-229E and 1.5 for HCV-OC43; log PFU/ml = 2.3 for HCV-229E and 1.34 for HCV-OC43). There were no false positive signals with other human respiratory pathogens: influenza virus, respiratory syncytial virus and adenovirus. Moreover, each assay was coronavirus serogroup-specific. These results demonstrate the potential usefulness of immunofluorescence with monoclonal antibodies and reverse transcriptase-polymerase chain reaction RNA amplification for the rapid detection of human coronaviruses in infected cell cultures. Both methods could be applied to clinical specimens for the diagnosis of human infections.

Antibodies, Monoclonal↗

PubMed2006

Effect of interactions between lower airway bacterial and rhinoviral infection in exacerbations of COPD.

STUDY OBJECTIVES: The inflammatory responses and associated clinical severity of COPD exacerbations are greatly variable, and the determinants of these factors are poorly understood. We examined the hypothesis that bacteria and viruses may modulate this heterogeneity and that interactions between bacterial and viral infection may affect changes in airway bacterial load and the clinical features and inflammatory responses of exacerbations in patients with COPD. DESIGN: Prospective cohort study. SETTING: Outpatient Department, London Chest Hospital, London, UK. PATIENTS: Thirty-nine patients with COPD. MEASUREMENTS: We prospectively studied 56 COPD exacerbations, obtaining clinical data and paired sputum and serum samples at baseline and exacerbation. Qualitative and quantitative microbiology, polymerase chain reaction detection for rhinovirus, and estimation of cytokine levels by enzyme-linked immunosorbent assay were performed. RESULTS: A total of 69.6% of exacerbations were associated with a bacterial pathogen, most commonly Haemophilus influenzae. Rhinovirus was identified in 19.6% of exacerbations. The rise in bacterial load at exacerbation correlated with the rise in sputum interleukin (IL)-8 (r = 0.37, p = 0.022) and fall in FEV1 (r = 0.35, p = 0.048). Exacerbations with both rhinovirus and H. influenzae had higher bacterial loads (10(8.56) cfu/mL vs 10(8.05)cfu/mL, p = 0.018) and serum IL-6 (13.75 pg/mL vs 6.29 pg/mL, p = 0.028) than exacerbations without both pathogens. In exacerbations with both cold symptoms (a marker of putative viral infection) and a bacterial pathogen, the FEV1 fall was greater (20.3% vs 3.6%, p = 0.026) and symptom count was higher (p = 0.019) than those with a bacterial pathogen alone. CONCLUSIONS: The clinical severity and inflammatory responses in COPD exacerbations are modulated by the nature of the infecting organism: bacterial and viral pathogens interact to cause additional rises in inflammatory markers and greater exacerbation severity.

Aged↗

PubMed1999

Rhinovirus identification by BglI digestion of picornavirus RT-PCR amplicons.

Rhinoviruses are the main cause of the common cold and precipitate the majority of asthma exacerbations. RT-PCR followed by internal probe hybridisation or Southern blotting, or nested PCRs are currently the most sensitive methods for their identification. However, none of the published techniques can differentiate satisfactorily rhinoviruses from other picornaviruses. Examination of the restriction maps of sequenced rhinoviruses, revealed a highly conserved BglI restriction site (GCCnnnnnGGC), located exactly in the middle of the 380-bp amplicon generated with the OL26-OL27 primer pair, which has been used extensively in the past to identify picornaviruses. Such a site was either not present, or positioned differently in other picornaviruses of known sequence. It was, therefore, considered that digestion of rhinovirus amplicons with this enzyme would result in two equal length fragments, generating a single 190-bp band in gel electrophoresis. In contrast, either one undigested 380-bp band or a double-band pattern would appear in amplicons from other picornaviruses. To test this hypothesis, Bgl digestions of OL26-OL27 amplicons from cultured and wild-type rhinoviruses, whose identity was confirmed by acid lability, as well as from echo, polio and coxsackie viruses were carried out. All rhinovirus samples were digested successfully generating single bands. Among the other picornaviruses, only 6.6% presented a single band pattern, while the rest were as predicted from the model. With a sensitivity of 100% and a specificity over 90%, the method described, which is rapid and remarkably easy to perform, can be used to distinguish rhinoviruses from other picornaviruses to a considerable extent.

Deoxyribonucleases, Type II Site-Specific↗

PubMed1981

Lysis of human B-lymphocyte-derived lymphoma/leukemia cells of established cell lines by interferon-activated natural killer (NK) cells.

Cultured cell lines derived from malignant Epstein-Barr virus (EBV)-negative B cells, and representative of the more common types of naturally occurring non-Hodgkin lymphomas and related leukemias, were found to be sensitive to lysis by human natural killer (NK) cells. The observed lysis of such cell lines was mediated by a population of interferon-augmentable, FcR-positive, non-adherent lymphoid cells, which were also able to kill the "standard" NK targets K562 and Molt-4. When the NK susceptibility of the neoplastic, EBV-negative B cells was compared to that of diploid, EBV-carrying, non-neoplastic B lymphoblastoid cell lines (BLCLs) and of the "standard" NK target K562, several distinct patterns were observed. The killing of the neoplastic B cell lines was significantly less than that of K562, but significantly greater than that of the EBV-derived BLCLs of non-neoplastic origin. An additional finding was a similar NK susceptibility profile for the neoplastic, true histiocytic cell line U-937 (i.e., K562 greater than U937 greater than BLCLs). Furthermore, all cell lines, with the exception of the BLCLs, could effectively compete for the observed killing in cold target inhibition assays. The implications of these findings are discussed in relation to both neoplastic and non-neoplastic targets of NK lysis.

B-Lymphocytes↗

PubMed1995

Human immune responses to influenza virus vaccines administered by systemic or mucosal routes.

Healthy adult volunteers were immunized by parenteral or oral routes with trivalent inactivated influenza vaccine (A/Chile/1/83 (H1N1), A/Mississippi/1/85 (H3N2), and B/Ann Arbor/1/86), or intranasally with live attenuated, cold-adapted influenza type A/Texas/1/85 (H1N1) reassortant virus. In all volunteers, cells spontaneously secreting IgA, IgG or IgM antibodies specific to influenza virus were detected in peripheral blood on days 6-13 after immunization, and specific IgA, IgG and IgM antibodies to influenza vaccine were measured in sera and external secretions (saliva and nasal lavage). Following systemic immunization, a raise in specific antibodies of all isotypes was observed in sera beginning on day 13. Although small variations in IgA and IgM antibodies in saliva and nasal lavages were detected, antigen-specific IgG significantly increased between days 13 and 27. Intranasal administration of attenuated virus induced IgA and IgG antibodies in serum as well as in secretions. Serum antibodies were not substantially influenced by oral immunization, only a small increase in all isotypes was observed in volunteers' sera 21 days after ingestion of vaccine. However, in secretions, antigen-specific IgA and IgG responses were detected one week after immunization and reached a peak response on day 20. These studies show that different routes of immunization can be effective for the induction of specific antibodies, and support the concept of the common mucosal immune system in humans by demonstrating that the oral or intranasal administration of antigen-induced specific antibodies of IgA isotype in external secretions, preceded by the transient appearance in peripheral blood of specific antibody-producing cells.

Administration, Intranasal↗