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.

Variant effect of first- and second-generation antihistamines as clues to their mechanism of action on the sneeze reflex in the common cold.

Treatment with first-generation antihistamines reduces sneezing, rhinorrhea, nasal mucus weight, and, in some instances, cough in subjects with experimental or natural colds; however, treatment with second-generation antihistamines has not been effective for these complaints in trials in subjects with natural colds. This article reports the negative results of a clinical trial with loratadine, a second-generation antihistamine, in adults in the rhinovirus challenge model. This finding in the highly controlled setting of the challenge model confirms the earlier negative studies with second-generation antihistamines in natural colds. First-generation antihistamines block both histaminic and muscarinic receptors as well as passing the blood-brain barrier. Second-generation antihistamines mainly block histaminic receptors and do not pass the blood-brain barrier. The effectiveness of first-generation antihistamines in blocking sneezing in colds may be due primarily to neuropharmacological manipulation of histaminic and muscarinic receptors in the medulla.

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.

Effectiveness of pseudoephedrine plus acetaminophen for treatment of symptoms attributed to the paranasal sinuses associated with the common cold.

BACKGROUND: Little data exist on the cause and treatment of subfacial pain and pressure and other discomfort attributed to the paranasal sinuses that develop early during the course of the common cold. The purpose of this study was to determine the efficacy of the combination of pseudoephedrine hydrochloride with acetaminophen for the treatment of early symptoms during colds, which are attributed by the patient to the sinuses. METHODS: Four hundred thirty subjects (216, pseudoephedrine and acetaminophen recipients; 214, placebo recipients) with cold symptoms of 48 hours or less who reported overall "sinus" symptoms of at least moderate severity were enrolled in this randomized double-blind placebo-controlled 2-dose study. Self-reported symptoms were scored (0 to 4, absent to severe) before and at 2 hours after the first and second doses. The 2 primary were measured 2 hours after the second dose were the overall sinus symptom assessment and a weighted composite assessment of sinus pressure, pain, and congestion (sinus symptoms). RESULTS: Compared with baseline, 2 hours after the second dose, the mean +/- SEM overall sinus symptom assessment score had decreased by 1.30 +/- 0. 06 in the pseudoephedrine and acetaminophen-treated subjects compared with 0.93 +/- 0.06 in the placebo-treated subjects (P< or = .029). The mean +/- SEM weighted average of sinus symptoms 2 hours after the second dose of study medication had decreased by 1.14 +/- 0.06 in the pseudoephedrine and acetaminophen-treated subjects compared with 0.84 +/- 0.06 in the placebo-treated subjects (P< or = .029). Reductions in similar magnitude were also observed for each of the individual sinus symptoms, and headache and rhinorrhea. Nervousness occurred in 4% of the pseudoephedrine and acetaminophen recipients compared with 0% of placebo recipients (P =.007). CONCLUSION: Our results suggest that pseudoephedrine plus acetaminophen is effective for relief of symptoms attributable to the paranasal sinuses that may develop early in the course of a cold. Arch Fam Med. 2000;9:979-985

Respiratory syncytial virus stimulation of vascular endothelial cell growth Factor/Vascular permeability factor.

We hypothesized that respiratory syncytial virus (RSV)-induced pathologies could be mediated, in part, by vascular active cytokines elaborated during virus infection. To address this hypothesis, we determined whether RSV stimulated vascular endothelial cell growth factor (VEGF)/vascular permeability factor (VPF) elaboration in vitro. Supernatants from unstimulated A549 cells and normal human bronchial epithelial cells contained modest levels of VEGF. In contrast, supernatants from RSV-infected cells contained elevated levels of VEGF/VPF. This stimulation was seen after as little as 2 h, was still prominent after 48 h, and, by immunoblot, was specific for the 165- and 121-amino acid isoforms of VEGF/VPF. It was not associated with significant cell cytotoxicity or alterations in VEGF messenger RNA. It did, however, require new protein biosynthesis. In accordance with these findings, the 165- and 121-amino acid isoforms of VEGF/VPF were also found in the nasal washings from patients with RSV infections. These studies demonstrate that RSV is a potent stimulator of VEGF/VPF elaboration and that, in vitro, this stimulation is mediated via a noncytotoxic translational and/or post-translational biosynthetic mechanism. VEGF/VPF may play an important role in the pathogenesis of RSV-induced disorders.

Lactoferrin and eosinophilic cationic protein in nasal secretions of patients with experimental rhinovirus colds, natural colds, and presumed acute community-acquired bacterial sinusitis.

To distinguish sinusitis from uncomplicated "colds," we examined lactoferrin and eosinophilic cationic protein (ECP) in nasal secretions. Lactoferrin titers were >/=1:400 in 4% of persons with uncomplicated colds and controls but in 79% of persons with sinusitis or purulent sputa. ECP levels were >200 ng/ml in 61% of persons with colds and >3,000 ng/ml in 62% of persons with sinusitis. Nasal lactoferrin helps distinguish sinusitis from colds.

Nose blowing propels nasal fluid into the paranasal sinuses.

Intranasal pressures were measured in adults during nose blowing, sneezing, and coughing and were used for fluid dynamic modeling. Sinus CT scans were performed after instillation of radiopaque contrast medium into the nasopharynx followed by nose blowing, sneezing, and coughing. The mean (+/-SD) maximal intranasal pressure was 66 (+/-14) mm Hg during 35 nose blows, 4.6 (+/-3.8) mm Hg during 13 sneezes, and 6.6 (+/-3.8) mm Hg during 18 coughing bouts. A single nose blow can propel up to 1 mL of viscous fluid in the middle meatus into the maxillary sinus. Sneezing and coughing do not generate sufficient pressure to propel viscous fluid into the sinus. Contrast medium from the nasopharynx appeared in >/=1 sinuses in 4 of 4 subjects after a nose blow but not after sneezing or coughing.

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.

Rhinovirus regulation of IL-1 receptor antagonist in vivo and in vitro: a potential mechanism of symptom resolution.

Rhinovirus (RV) upper respiratory tract infections are prototypic transient inflammatory responses. To address the mechanism of disease resolution in these infections, we determined if RV stimulated the production of the IL-1 receptor antagonist (IL-1ra) in vivo and in vitro. In contrast to IL-1alpha and IL-1beta, immunoreactive IL-1ra was readily detected in the nasal washings of normal human volunteers. Symptomatic RV infection caused a small increase in IL-1alpha, a modest increase in IL-1beta, and an impressive increase in IL-1ra. Maximal induction of IL-1alpha and IL-1beta was transiently noted 48 h after RV infection. In contrast, maximal induction of IL-1ra was prolonged appearing 48-72 h after RV infection. These time points corresponded to the periods of peak symptomatology and the onset of symptom resolution, respectively. Western analysis of nasal washings demonstrated that RV stimulated the accumulation of intracellular IL-1ra type I in all and secreted IL-1ra in a subset of volunteers. Unstimulated normal respiratory epithelial cells contained intracellular IL-1ra type I mRNA and protein. RV infection increased the intracellular levels and extracellular transport of this IL-1ra moiety without causing significant changes in the levels of IL-1ra mRNA. IL-1ra may play an important role in the resolution of RV respiratory infections. RV stimulates epithelial cell IL-1ra elaboration, at least in part, via a novel translational and/or posttranslational mechanism.

Acute community acquired bacterial sinusitis: To treat or not to treat.

The paranasal sinuses, normally sterile, are prone to bacterial invasion as a complication of viral illnesses such as the common cold. Using computed tomograms, abnormalities of the sinuses can be seen in 90% of healthy adults with upper respiratory tract infections; only 2% of these patients will develop bacterial sinusitis. Possible rationales for antibiotic treatment of sinusitis include the normal sterility of the sinuses, the clinical morbidity associated with sinusitis, the possibility of serious intracranial and periorbital complications in untreated cases, and the possible progression of acute infections to chronic sinus disease. Evidence from the literature supports antibiotic treatment of sinusitis to eradicate infection and to reduce symptoms. There is insufficient literature evidence to prove that antibiotic treatment reduces serious complications or reduces progression to chronic sinus disease. Treatment should include an antimicrobial with a spectrum likely to cover the important pathogens, including those with high levels of resistance.

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.

Prechallenge antibodies moderate disease expression in adults experimentally exposed to rhinovirus strain hanks.

This double-blind study determined the influence of serum neutralizing antibody titers on the rate of infection and magnitude of disease expression after experimental exposure of adult volunteers to rhinovirus strain Hanks (RV-H). A total of 133 healthy volunteers were tested for antibody status, cloistered for a 6-day period, and challenged with RV-H at the end of the first cloister day. On these days, response to viral challenge is assessed with symptom diaries and physical examinations. The low-titer infected group was significantly different from the intermediate-titer infected and the uninfected groups in terms of postchallenge nasal and throat symptoms, expelled secretion weights, nasal mucociliary clearance rates, and frequency of negative middle ear pressures. A similar trend held for the infected high-titer vs. low-titer group comparisons. These data show that high homotypic serum neutralizing antibody titers are associated with protection from infection and lessened signs and symptoms following experimental RV-H exposure.

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.

Low plasma levels of adrenocorticotropic hormone in patients with acute influenza.

Plasma levels of adrenocorticotropic hormone (ACTH) and cortisol were measured in young adults with influenza virus type A (H3N2) infection for whom cultures were positive and in comparable controls without symptoms or other evidence of illness. The mean plasma ACTH level +/- SE in 19 patients with acute influenza was 13.5 +/- 2.1 pg/mL compared with 23 +/- 3.2 pg/mL in 11 controls (P = .02). Mean plasma ACTH levels +/- SE had risen to 21 +/- 4.1 pg/mL in specimens obtained from patients during convalescence. The mean plasma cortisol level +/- SE in patients with acute influenza was 13.7 +/- 1.4 micrograms/dL compared with 10.8 +/- 1.0 micrograms/dL in controls (P = not significant). ACTH levels in individual controls were relatively higher than their cortisol levels, but ACTH levels in patients tended to be lower than cortisol levels in paired specimens. These findings suggest that influenza virus type A infection may have an inhibitory effect on the production or release of ACTH.

Viral-induced rhinitis.

Upper respiratory viruses cause self-limited illness characterized by acute rhinitis. In rhinovirus colds the symptoms are thought to be caused by the host response rather than viral damage of the nasal epithelium. Rhinovirus triggers an inflammatory cascade, evidenced by the presence of inflammatory mediators (e.g., IL-8) and proinflammatory cytokines (e.g., kinins) in nasal secretions, which results in symptomatic illness. In contrast to rhinovirus and coronavirus, which do not cause discernible epithelial damage, influenza virus and adenovirus do damage the nasal epithelium. Appropriate antiviral therapy will depend on the causative virus. Treatment of rhinovirus colds may require an antiviral agent (e.g., interferon alpha) in combination with antiinflammatory medication.

Efficacy of brompheniramine maleate for the treatment of rhinovirus colds.

We tested the efficacy of brompheniramine maleate in a large randomized, controlled trial of volunteers with experimental rhinovirus colds. Brompheniramine (12 mg) or placebo was administered at 8:00 A.M. and 8:00 P.M. for < or = 4 days after the onset of symptoms (24, 36, or 48 hours after virus challenge). During the first 3 days of treatment (the first 4 days after virus challenge), nasal secretion weights were lower for infected evaluable subjects receiving brompheniramine (n = 113) than for controls (day 1: 4.3 g vs. 6.8 g; day 2: 4.8 g vs. 7.7 g; and day 3: 3.3 g vs. 5.3 g) (P < or = .03), as were rhinorrhea scores (day 1: 0.6 vs. 0.8; day 2: 0.5 vs. 0.8; and day 3: 0.3 vs. 0.5) (P < .03), sneeze counts (day 1: 1.8 vs. 3.6; day 2: 2.1 vs. 5.1; and day 3: 1.3 vs. 3.3) (P < or = .001), and sneeze severity scores (day 1: 0.3 vs. 0.6; day 2: 0.25 vs. 0.7; and day 3: 0.2 vs. 0.4) (P < .001) (n = 112). Cough counts were lower after day 1 of treatment for the brompheniramine group than for controls (4.7 vs. 7.9) (P = .05) (day 2 after virus challenge), and other symptoms were modestly reduced or were unaffected in the brompheniramine group. Total symptom scores were also lower for the brompheniramine group than for controls on treatment days 1 (4.8 vs. 6.0) (P = .03) and 2 (4.1 vs. 5.6) (days 2 and 3 after virus challenge) (P = .003). Treatment with brompheniramine was associated with the adverse effects of somnolence (n = 3) and confusion (n = 1). Brompheniramine was efficacious treatment for the sneezing, rhinorrhea, and cough associated with rhinovirus colds.

Effectiveness of clemastine fumarate for treatment of rhinorrhea and sneezing associated with the common cold.

Limited data support the use of first-generation antihistamines for treatment of the common cold. The purpose of this study was to test the effectiveness of clemastine fumarate, a first-generation antihistamine, for treatment of sneezing and rhinorrhea associated with naturally occurring common colds. Four hundred three subjects (202 clemastine fumarate recipients and 201 placebo recipients) who reported new onset (< 24 hours) of cold symptoms that included rhinorrhea or sneezing were studied. At baseline (day 1), the mean symptom-severity scores +/- SEM for the clemastine fumarate and placebo groups were not significantly different. The mean rhinorrhea-severity score +/- SEM was not different on day 2; however, on day 3, the mean rhinorrhea-severity score +/- SEM was 1.02 +/- 0.07 for the clemastine fumarate group and 1.39 +/- 0.07 for the placebo group (P < .001). This treatment effect persisted on day 4. A significant effect on sneezing was noted on days 2-4. Sedation occurred in 14% of the clemastine fumarate-treated subjects and 1.5% of the placebo-treated subjects (P < .0001).