Radiopaque contrast dye in nasopharynx reaches the middle ear during swallowing and/or yawning.

CONCLUSION: Contrast dye in the nasopharynx reaches the middle ear during swallowing and yawning in normal adults. This suggests that displacement of bacteria in nasopharyngeal secretion to the middle ear may occur frequently during sleep. OBJECTIVE: The middle ear is sterile under normal conditions. The purpose of this study was to examine by means of CT whether radiopaque contrast dye in the nasopharynx would reflux into the middle ear of normal adults during swallowing and/or yawning. MATERIAL AND METHODS: Six normal adult volunteers were studied. Contrast dye was kept at the orifices of the Eustachian tube during swallowing and/or yawning by placing volunteers in either a head-down or lateral decubitus position. Reflux was determined by the presence of contrast dye in the middle ear on CT scanning of the temporal bone. RESULTS: Two of the three volunteers in each group (four out of six in total) had contrast material detected in one or both middle ear cavities.

Antitussive effect of guaifenesin in young adults with natural colds. Objective and subjective assessment.

The efficacy of guaifenesin in reducing cough frequency in young adults with acute respiratory disease was evaluated by both an objective cough counting system and a questionnaire. A guaifenesin cough preparation and the syrup vehicle were administered in a double-blind manner. Coughs were recorded on tape over a 24-hour baseline evaluation period and a 36-hour treatment period for 42 patients. A pronounced diurnal variation in cough frequency was observed. The evaluation of efficacy was based upon comparisons between equivalent six-hour time periods of successive days. No antitussive effect of guaifenesin was demonstrated. The questionnaire was administered to 65 patients, including the 42 whose coughs were recorded. Of 26 patients with productive cough receiving guaifenesin, 25 (96 percent) reported a decrease in sputum thickness compared to 13 (54 percent) of 24 patients receiving the vehicle (p = 0.01, Fisher exact test). Twenty-three of 26 (88 percent) patients receiving guaifenesin also reported reduction in sputum quantity compared to 15 of 24 (62.5 percent) receiving the vehicle (p = 0.07, Fisher exact test). The diurnal variation in cough frequency measured by the tape recording was not apparent from the subjective cough frequency estimates obtained by the questionnaire.

A double-blind, placebo-controlled clinical trial of the effect of chlorpheniramine on the response of the nasal airway, middle ear and eustachian tube to provocative rhinovirus challenge.

This paper presents the results of a randomized, double-blind, placebo-controlled study of the efficacy of chlorpheniramine in relieving the symptoms and attenuating the pathophysiologic correlates of a rhinovirus "common cold." Forty healthy, adult, nonatopic subjects were randomly assigned to one of two treatment groups: active drug and placebo. On study Day 0, all subjects were challenged intranasally with rhinovirus type 39 (dose = 100 TCID50). Subjects were cloistered from Day 2 to Day 7, at which time they were treated with either chlorpheniramine or placebo. From 3 days before challenge to study Day 19, subjects had nasal patency assessed by rhinomanometry, eustachian tube function assessed by the 9-step test and sonotubometry, middle ear pressure assessed by tympanometry and nasal clearance assessed by the dyed-saccharin technique. Symptom diaries were maintained throughout the period of follow-up. During cloister, symptoms also were scored by interview, nasal secretions were quantified and nasal washings were performed for viral culture. Results showed that 19 (95%) subjects in the active-treatment group and 18 (90%) subjects in the placebo-treatment group shed virus. Symptomatic colds were observed in 63% of the active-treated and 83% of the placebo-treated subjects. Symptoms increased on Day 1 and peaked at Days 4 to 5. Detrimental changes in other measured functions consistent with those previously reported were observed. During the period of treatment, significant differences in the average symptom scores favoring the active-treatment group were observed for sneezing. Also, weight of expelled secretions was greater and mucociliary clearance rate less on some cloister days for the placebo-treated group. No significant differences between treatment groups in the objective measures of nasal congestion or the response of the middle ear and eustachian tube were documented.

Is histamine responsible for the symptoms of rhinovirus colds? A look at the inflammatory mediators following infection.

In an attempt to identify inflammatory mediators that may contribute to rhinorrhea, nasal congestion and other cold symptoms, we recruited 40 healthy young adults (median age, 20) for provocative rhinovirus challenge. Mediators measured included histamine, kinins and enzymes with arginine esterase activity. Volunteers were inoculated with rhinovirus or a sham inoculum. Nasal secretions for viral culture were obtained daily, and volunteers were deemed infected if they shed virus or had a 4-fold or greater increase in serum antibody titer. The virus-infected group was subdivided using the Jackson criteria into an ill or non-ill group; each group was compared to the control group. Of the 27 virus-inoculated subjects, 25 had positive cultures for the challenge virus, and 15 became ill. None of the controls had a positive culture. All variables measured--except histamine--grew stronger in direct relationship with the symptoms as the cold increased in severity. In the infected-ill group, the mean kinin level increased more than 10-fold over baseline. The kinin level remained relatively unchanged in the control and non-ill groups. Similar results were found for levels of albumin and enzymes with arginine esterase activity. Histamine levels remained constant in both the infected-ill and non-ill groups, which suggests that mast cells and basophils do not participate in the pathophysiology of rhinovirus infections and that antihistamines should be ineffective in treating rhinovirus colds. Since volunteers who developed cold symptoms exhibited a notable increase in kinin, a potent inflammatory mediator, we recommend further study of a kinin antagonist in reducing nasal symptoms.

Anti-interferon antibody increases rhinovirus isolation rates from nasal wash specimens containing interferon-alpha 2.

Isolation of rhinoviruses from nasal secretions may be delayed or prevented by exogenously applied interferon which is carried over into nasal wash specimens. In studies of interferon-alpha 2 treated volunteers with experimental rhinovirus infection, we determined that incorporation of antiinterferon antibody into collection broth significantly increased isolation rates (84% increase) and the proportion of monolayers positive for CPE (155% increase), as compared to plain collection broth.

Modification of experimental rhinovirus colds by receptor blockade.

Human rhinovirus (HRV) infection can be inhibited in vitro by antibody directed against the cellular receptor for the major HRV group representing 90% of serotypes. We assessed the prophylactic effectiveness and safety of intranasally administered rhinovirus receptor murine monoclonal antibody (RRMA) in two double-blind, place-controlled, randomized studies of volunteers experimentally inoculated with HRV-39. In the first study, RRMA administration (135 micrograms/subject in 9 applications, -17 to +48 h) did not reduce infection (RRMA 12/15 vs. placebo 13/15) or illness (8/12 vs. 7/13) rates or modify the clinical course of experimental HRV-39 colds. In the second trial, a higher RRMA dosage (1 mg/subject in 10 applications, -3 to +36 h), similarly did not reduce overall infection (11/13 vs. 12/13) or illness (7/11 vs. 9/12) rates, but was associated with a 1-2 day delay in the onset of viral shedding and cold symptoms and with significant reductions in viral titers and nasal symptoms on the second day after challenge and in mucus weights on the third day after challenge. No toxicity related to RRMA was recognized. The results indicate that intranasal RRMA modified infection and illness after experimental HRV-39 challenge and suggest that blockade of host cell receptors offers a novel antiviral approach against HRV infections.

Prophylactic efficacy and tolerance of low-dose intranasal interferon-alpha 2 in natural respiratory viral infections.

The prophylactic activity of intranasal human interferon-alpha 2 (HuIFN-alpha 2) was determined in a randomized, double-blind, placebo-controlled study. Healthy, working adults self-administered sprays of HuIFN-alpha 2(1.25 X 10(6) IU; n = 142) or placebo (n = 145) twice daily. Drug administration was stopped after 12 days because of the frequent occurrence of nasal irritation manifested by blood-tinged nasal mucus (44% HuIFN-alpha 2 versus 15% placebo, P less than 0.001) and associated nasal mucosal abnormalities. Over 80% of volunteers had participated in a similar field trial conducted 7 months earlier; no evidence of cumulative toxicity was detected. HuIFN-alpha 2 administration did not decrease the occurrence of illnesses associated with rhinorrhea, cough, or feverishness as compared to placebo, but the number of laboratory-documented respiratory viral infections was small (6 HuIFN-alpha 3 placebo). Intranasal HuIFN-alpha 2 1.25 X 10(6) IU twice daily was associated with significant local intolerance.

The influence of signal variation, bias, noise and effect size on statistical significance in treatment studies of the common cold.

Many groups are working on new and improved methods of common cold treatment that include antivirals, synthetic viral receptor, compounds which block symptom pathways, and combinations of these approaches. Because the common cold syndrome is in large part subjective, symptom measurement remains an important parameter in evaluating the effectiveness of cold treatments. This review examines the features of the experimental and natural cold testing methods that effect recognition of illness signal and influence its variance and strength. Also, the importance of changes in signal variance and in the magnitude of therapeutic effect size as they relate to statistical probability were compared using a symptom data set from young adults with experimental rhinovirus colds.

Rhinovirus inactivation by nasal tissues treated with virucide.

Rhinovirus colds may be transmitted by hand-to-hand contact followed by self-inoculation of nasal and/or conjunctival mucosa with virus contaminating the fingertips. The purpose of this study was to determine whether impregnation of nasal tissues with virucidal compounds could prevent rhinovirus from passing through the tissue and thus provide a means of preventing hand contamination during nose blowing. Paper tissues treated with a combination of citric acid, malic acid, and sodium laruryl sulfate were compared to placebo tissues containing sodium saccharin. Recovery of infectious virus was significantly reduced by passage of the virus-containing medium through virucidal versus placebo tissue (1/18 vs. 17/18 respectively, P less than 0.001, Fisher exact test). The virucidal effect of treated tissues was demonstrated for multiple rhinovirus serotypes suspended in either cell culture medium or nasal mucus. Virus contained in mucus from infected volunteers was also inactivated.

Frequency of percutaneous injuries requiring postexposure prophylaxis for occupational exposure to human immunodeficiency virus.

New recommendations regarding prophylaxis of healthcare workers exposed to human immunodeficiency virus (HIV) prompted us to examine the frequency and nature of percutaneous injuries at this hospital. Four previously defined risk factors for transmission of HIV were evaluated. Between 1993 and 1995, 1,070 percutaneous injuries were reported, including 11 in which the source patient had acquired immunodeficiency syndrome (AIDS). Five of these injuries involved at least one risk factor for transmission. No source patient was found to have AIDS as a result of testing following exposure. We conclude that high-risk injuries are infrequent and that postexposure prophylaxis will not increase costs greatly at this medical center.

Rhinovirus antibodies in an isolated Amazon Indian tribe.

In early 1985, the Parakana-Apiterewa, a small, primitive Indian tribe, was contacted in the southern Amazon Basin. The tribe was thought to have been totally isolated from civilization until recent development of their land. Blood specimens were collected in 1985, shortly after the discovery of the tribe, and analyzed for the presence of rhinovirus-neutralizing antibody to nine different immunotypes. Six to forty-seven percent of the serum samples tested contained antibody to at least one immunotype of rhinovirus. The prevalence of rhinovirus antibody in the Parakana-Apiterewa Indians was similar to that reported in United States populations, suggesting that there had been considerable direct or indirect contact in the past between tribe members and persons in the outside world.

The University of Virginia health promotion and disease prevention program.

INTRODUCTION: Proof of effectiveness now exists for many health promotion and disease prevention practices, yet the importance of this knowledge is not widely appreciated, and a large percentage of the population does not receive this care. Universities with comprehensive academic medical centers are particularly appropriate places for providing health promotion programs. The University of Virginia began a health promotion and disease prevention program for employees in 1990. METHODS: Periodic health risk appraisal, with follow-up and selected interventions, is offered to approximately 14,000 employees as a cost-free fringe benefit. Health risks are assessed with a modification of the Carter Center Health Risk Appraisal. Results are given to participants in group sessions; referrals are made for clinical preventive services and interventions, as needed. RESULTS: During the first three years, 29% of the employee population participated in the program. Participants were more likely to be young, female and not African American. Nearly 96% had one or more risk factors, with an average of 3.6 risk factors overall. Participants on average had 1.8 risk factors for cardiovascular disease; 0.3 for cancer; 0.6 for injury; 0.1 for alcohol abuse; and 0.7 for mental health. Nonparticipants were not receiving similar comprehensive health risk appraisal elsewhere. CONCLUSIONS: University of Virginia employees have multiple health risks, not detected through their usual health care, for which effective interventions are available. This population probably reflects conditions throughout the state and nation. Academic medical centers should place high priority on establishing health promotion programs as part of their responsibilities to society.

Topical treatment of herpes labialis with chloroform.

The efficacy of topical chloroform treatment of herpes labialis (HL) was evaluated in 50 patients with culture-verified HL. Treatment was begun within 48 hours of lesion onset, with either chloroform or camphor-in-oil placebo applied locally once a day for three days. Patients were observed daily by one investigator who also cultured and photographed the lesions. The photographs were evaluated by two other investigators. By direct observation, the time for scab formation was significantly less in the group treated with chloroform (P less than .01). No difference in time to healing was noted. Blind evaluation of the serial photographs showed a trend for more rapid scab formation and healing in patients treated with chloroform, but the differences were not significant. The minimal benefit derived from topical chloroform therapy of HL does not appear sufficient to recommend its routine use.

Types of stressors that increase susceptibility to the common cold in healthy adults.

Two-hundred seventy-six volunteers completed a life stressor interview and psychological questionnaires and provided blood and urine samples. They were then inoculated with common cold viruses and monitored for the onset of disease. Although severe acute stressful life events (less than 1 month long) were not associated with developing colds, severe chronic stressors (1 month or longer) were associated with a substantial increase in risk of disease. This relation was attributable primarily to under- or unemployment and to enduring interpersonal difficulties with family or friends. The association between chronic stressors and susceptibility to colds could not be fully explained by differences among stressed and nonstressed persons in social network characteristics, personality, health practices, or prechallenge endocrine or immune measures.

State and trait negative affect as predictors of objective and subjective symptoms of respiratory viral infections.

State and trait negative affect (NA) were measured in healthy people immediately before an illness was induced through exposure to a respiratory virus. State NA, disease-specific health complaints (e.g., runny nose, congestion, and sneezing), and an associated objective marker of disease severity (mucus secretion weights) were assessed daily during the illness. Baseline trait and state NA were both associated with increased numbers of subsequent complaints. Although greater numbers of complaints among people high in state NA were explicable in terms of greater disease severity, the association of trait NA and symptoms was independent of objective disease. The trait NA complaint association was also independent of state NA and hence not attributable to trait-elicited state affect. Greater trait NA was associated with biases in complaining during but not before illness. This suggested failure to discriminate between symptoms rather than increased sensitivity or hypochondriacal response.

The impact of personality on the reporting of unfounded symptoms and illness.

This study examined the role of personality in the reporting of symptoms and illness not supported by underlying pathology. After assessment of the Big Five personality factors, 276 healthy volunteers were inoculated with a common cold virus. On each of the following 5 days, objective indicators of pathology, self-reported symptoms, and self-reported illness onset were assessed. Neuroticism was directly associated with reports of unfounded (without a physiological basis) symptoms in individuals at baseline and postinoculation in those with and without colds. Neuroticism was also indirectly associated with reports of unfounded illness through reports of more symptoms. Openness to Experience was associated with reporting unfounded symptoms in those with verifiable colds, whereas Conscientiousness was associated with reporting unfounded illness in those who were not ill.

Otologic manifestations of experimental rhinovirus infection.

Episodes of acute otitis media are commonly associated with viral upper respiratory tract infections. Rhinoviruses account for approximately 40% of these infections, and were previously shown to alter eustachian tube function and middle ear pressures. However, progression to otitis media has not been prospectively documented. In the present study, changes in tympanometric pressures and otoscopic findings resulting from experimental intranasal rhinovirus type-39 inoculation were documented in 60 adult volunteers. Fifty-seven (95%) subjects became infected and 34 (60%) of these had a clinical cold. Prior to viral inoculation, 3 (5%) subjects had middle ear pressures of less than -100 mm H2O and two of these subjects developed middle ear effusions following infection. In all, 22 (39%) subjects developed middle ear pressures of less than -100 mm H2O. No subject with normal middle ear pressures prior to infection developed evidence of effusion. This study extends the otologic manifestations of rhinovirus infection to include otitis media. Furthermore, these results support the hypothesized relationship between upper respiratory tract infections, eustachian tube dysfunction, and otitis media.

Microbiology of chronic frontal sinusitis.

OBJECTIVES: To determine bacterial and fungal organisms that are present in patients undergoing surgery for chronic frontal sinusitis. STUDY DESIGN: Retrospective, nonrandomized study. METHODS: Retrospective, nonrandomized bacterial and fungal cultures were performed on 46 sinus aspirates obtained by frontal sinus trephination performed on 30 consecutive patients with chronic frontal sinusitis. RESULTS: Six patients were having sinus surgery for the first time, 19 patients had undergone prior functional endoscopic sinus surgery without instrumentation of the frontal sinus/recess, and the third group included 5 patients who had undergone prior frontal sinus/recess surgery. Preoperative computed tomography scan of the frontal sinuses revealed complete opacification in 63% (29/46 frontal sinuses) and partial opacification in 22% (10/46), and no data were available for 15% (7/46). Aerobic cultures revealed that 38% (13/35 cultures) had no growth, 21% (7/35) grew Staphylococcus aureus, 21% (7/35) grew coagulase-negative Staphylococcus, 9% (3/35) grew Haemophilus influenzae, and 26% (9/35) grew a variety of other organisms. Anaerobic cultures were positive in 3% (1/32) of sinuses, and fungal cultures were positive in 4% (1/24). Haemophilus influenzae was most common in primary cases, whereas coagulase-negative Staphylococcus was most common in patients undergoing revision frontal sinus surgery. There were no other significant differences between cultures from patients undergoing revision frontal sinus surgery, revision functional endoscopic sinus surgery without prior frontal surgery, and primary surgery. CONCLUSIONS: This study suggests that organisms involved in chronic inflammatory disease of the frontal sinus may change after previous sinus surgery. The study failed to support a significant role for anaerobes. The role for coagulase-negative Staphylococcus as a potential pathogen or a contaminating agent remains unclear.

Prechallenge antibodies: moderators of infection rate, signs, and symptoms in adults experimentally challenged with rhinovirus type 39.

This study determined the influence of serum neutralizing antibody titers on infection rate, symptom manifestations, and provoked signs and pathophysiologies in adults experimentally exposed to rhinovirus type 39 (RV-39). Antibody status was determined for 151 healthy volunteers who were then cloistered in a hotel for 6 days. At the end of the first cloister day, the volunteers were challenged with RV-39 in a median tissue culture infective dose of 100. On each of the 6 days, a nasal examination was performed, symptoms were scored, and objective tests of nasal mucociliary function, nasal airway patency, secretion production, and middle ear pressures were completed. Both subjects and investigators were blinded to the prechallenge serum homotypic antibody titers of the subjects. Four subjects presented with a wild virus and were excluded from the analysis. Of the 147 included subjects, prechallenge serum antibody titers to RV-39 were low (under 2) in 56 subjects, intermediate (2 to 8) in 51 subjects, and high (above 16) in 40 subjects. The high-titer group was significantly different from the low-titer group with respect to viral shedding, symptom load, subjective extent of illness, and secretion production, as well as in the frequency of subjects with abnormal nasal mucociliary clearance and positive middle ear pressures. The study results document that for experimental RV-39 exposure, high levels of homotypic serum neutralizing antibody titers are associated with protection from infection and a lessened degree of disease expression, but not with a reduction of otologic complications.

Comparative evaluation of cefuroxime axetil and cefaclor for treatment of acute bacterial maxillary sinusitis.

Cefuroxime axetil, a new beta-lactamase-stable cephalosporin, was compared with cefaclor for the treatment of acute bacterial maxillary sinusitis in 106 adult patients. Direct sinus aspirations for quantitative bacterial culture were done for all patients before treatment; aspiration was repeated for most patients after treatment. Pretreatment sinus aspirates were positive for 63 of 134 sampled sinuses. Of specimens yielding at least 10(4) CFU/mL, Haemophilus influenzae (38%) and Streptococcus pneumoniae (37%) were the most common pathogens. Ten (42%) of 24 strains of H influenzae, 2 (40%) of 5 Haemophilus parainfluenzae, and all 3 isolates (60%) of Branhamella catarrhalis produced beta-lactamase. Cefuroxime axetil, 250 mg twice a day, was compared with cefaclor, 500 mg three times a day. Among culture-positive sinuses, bacteriologic cure was achieved in 36 (95%) of 38 sinuses and 15 (71%) of 21 sinuses treated with cefuroxime axetil and cefaclor, respectively. The overall frequencies of adverse events were similar between drugs, although cefuroxime axetil was associated with more frequent diarrhea. Cefuroxime axetil was an effective therapy for the treatment of acute bacterial maxillary sinusitis in adults.