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PubMed2001

Expression of C-reactive protein in the human respiratory tract.

C-reactive protein (CRP) is a normal constituent of human sera synthesized by hepatocytes and induced by proinflammatory cytokines. The function of this acute-phase reactant includes activation of complement and enhancement of opsonophagocytosis. CRP binds to phosphorylcholine (ChoP), a constituent of eukaryotic membranes that is also found on the cell surface of major bacterial pathogens of the human respiratory tract, including Streptococcus pneumoniae and Haemophilus influenzae. The presence of CRP on mucosal surfaces and role in innate immunity in the human respiratory tract where ChoP-containing organisms reside have not been previously studied. We have shown using a monoclonal antibody to CRP that CRP is present in inflamed (0.17 to 42 microg/ml) and uninflamed (<0.05 to 0.88 microg/ml) secretions from the human respiratory tract in sufficient quantities for an antimicrobial effect. In addition, the CRP gene was expressed in epithelial cells of the human respiratory tract using in situ hybridization on nasal polyps and reverse transcriptase PCR of pharyngeal cells in culture. The complement-dependent bactericidal activity of normal nasal airway surface fluid and sputum against ChoP-expressing H. influenzae was abolished when the secretions were pretreated to remove CRP. In summary, the results indicate that CRP is present in secretions of the human respiratory tract, that human respiratory epithelial cells are capable of CRP expression, and that this protein may contribute to bacterial clearance in the human respiratory tract.

Adult↗

PubMed2004

Gender differences in hospitalization rates for respiratory tract infections in Danish youth.

Overall morbidity and mortality rates in childhood are reported to be higher in males than females. As respiratory tract infections constitute the leading cause of childhood hospitalization, we examined the gender difference in rates of hospitalization due to respiratory tract infections in Danish youth (under age 25). We studied a total of 64,049 hospitalizations for otitis media, pneumonia, influenza, and other acute respiratory tract infections from 1995 to 1999, with calculation of hospitalization rates by age and gender. The male-female hospitalization rate ratio (HRR) for admission due to a respiratory tract infection decreased from 1.45 (95% confidence interval (CI) 1.42-1.48) in the age group 0 - < 5 y, to 1.62 (95% CI 1.55-1.70) in the age group 5 - < 10 y, 1.13 (95% CI 1.04-1.22) in the age group 10 - < 15 y, 0.83 (95% CI 0.76-0.90) in the age group 15 - < 20 y, and 0.87 (95% CI 0.80-0.95) in the age group 20 - < 25 y. In young children, boys were hospitalized more often than girls, but the reverse applied in children and adolescents 15-25 y of age. The study generates the hypothesis that gender plays a role in the susceptibility for respiratory infections in early childhood.

Adolescent↗

PubMed2005

Differential regulation of dual NADPH oxidases/peroxidases, Duox1 and Duox2, by Th1 and Th2 cytokines in respiratory tract epithelium.

Partially reduced metabolites of molecular oxygen, superoxide (O2-) and hydrogen peroxide (H2O2), are detected in respiratory tract lining fluid, and it is assumed that these are key components of innate immunity. Whether these reactive oxygen species (ROS) are produced specifically by the respiratory epithelium in response to infection, or are a non-specific by-product of oxidant-producing inflammatory cells is not well characterized. Increasing evidence supports the hypothesis that the dual function NAD(P)H oxidases/peroxidases, Duox1 and Duox2, are important sources of regulated H2O2 production in respiratory tract epithelium. However, no studies to date have characterized the regulation of Duox gene expression. Accordingly, we examined Duox1 and Duox2 mRNA expression by real-time PCR in primary respiratory tract epithelial cultures after treatment with multiple cytokines. Herein, we determined that Duox1 expression was increased several-fold by treatment with the Th2 cytokines IL-4 and IL-13, whereas Duox2 expression was highly induced following treatment with the Th1 cytokine IFN-gamma. Duox2 expression was also elevated by polyinosine-polycytidylic acid (poly(I:C)) and rhinovirus infection. Diphenyleneiodonium (DPI)-inhibitable apical H2O2 production was similarly increased by the addition of Th1 or Th2 cytokines. These results demonstrate for the first time the regulation of Duox expression by immunomodulatory Th1 and Th2 cytokines, and suggest a mechanism by which ROS production can be regulated in the respiratory tract as part of the host defense response.

Animals↗

PubMed2004

[Drug-resistance analysis of Gram-negative bacilli producing extended-spectrum beta-lactamases in lower respiratory tract infection].

OBJECTIVE: To analyze occurrence of Gram-negative bacteria producing extended-spectrum beta-lactamase (ESBL) in patients with lower respiratory tract infection and assess their drug sensitivity to provide evidence for clinical management of lower respiratory tract infection with drug-resistant ESBL-producing bacteria. METHODS: A total of 312 Gram-negative bacterial strains were isolated from patients with lower respiratory tract infection and identified for the presence of ESBL by Vitek ESBL detection test and double-disk synergy tests as well as standard disk diffusion test. The effects of 10 antibacterial drugs on ESBL-producing strains were compared. RESULTS: A rate of 20.1% of the isolated strains were identified to produce ESBLs, including Klebsiella Pneumoniae, Escherichia coli, Enterobacter cloacae, Pseudomonas aeruginasa and Klebsiella oxytocla (accounting for 30.1%, 29.1%, 27.0%, 11.3%, and 2.5%, respectively, of the ESBL-producing strains). Imipenem possessed the most powerful antibacterial activity against ESBL-producing strains. CONCLUSIONS: Attention should be given to lower respiratory tract infections with ESBL-producing Gram-negative bacilli, and imipenem can be the primary choice for fighting such infections.

Drug Resistance, Bacterial↗

PubMed1995

Increased nitric oxide in exhaled air of normal human subjects with upper respiratory tract infections.

Viral infection may induce the expression of nitric oxide (NO) synthase, resulting in increased NO formation that has an antiviral effect. NO may be produced by various cells of the upper and lower respiratory tract, and may be detected in the exhaled air. We have studied the levels of exhaled NO in 18 normal subjects during symptomatic upper respiratory tract infections and during recovery 3 weeks later. Exhaled NO was measured using a modified chemiluminescence analyser. At the time of symptoms of upper respiratory tract infection, the peak exhaled NO values were 315 +/- 57 ppb (mean +/- SEM) and decreased to 87 +/- 9 ppb during recovery. Recovery values of exhaled NO were similar to those reported in age-matched normal control subjects (88 +/- 3 ppb, n = 72). These findings suggest that symptomatic upper respiratory tract infections markedly increase the concentration of NO in exhaled air. This may reflect the induction of nitric oxide synthase (NOS) in upper and lower respiratory tract, and may be relevant to viral exacerbations of asthma.

Adult↗

PubMed2007

Use of diagnostic algorithms and new technologies to study the incidence and prevalence of viral upper respiratory tract infections and their complications in high risk populations.

PURPOSE OF REVIEW: Most studies on the natural history of viral upper respiratory tract infections and their complications rely for ascertainment on self-assessed cold/flu illness or the identification of presumed complications. The criteria for cold/flu definition, however, are variable within and between individuals and illness is not prerequisite for a viral upper respiratory tract infection. These factors bias estimates of the incidence and prevalence of viral upper respiratory tract infections and their complications. Here we review new methodologies that can be adapted for use in future studies to refine those estimates. RECENT FINDINGS: We present a theoretical basis for standardized assignment of cold/flu episodes using a minimal algorithm template that operates on a structured set of symptoms/signs. We emphasize the greater accuracy of information derived from longitudinal studies that incorporate identification algorithms and assay of nasal secretions for causal virus by polymerase chain reaction and for proinflammatory chemicals to confirm nasal inflammation. SUMMARY: The methodologies and sampling strategies that we describe hold promise for better characterizing the incidence of complications for symptomatic and asymptomatic expressions of a viral upper respiratory tract infection caused by specific viruses. These data can then be used to estimate the efficacy and efficiency in a specified target population of prophylactic or intercurrent treatments to prevent the complications.

Algorithms↗

PubMed1994

[Rapid detection for antigens of respiratory tract viruses by using series of monoclonal antibody].

A series of monoclonal Antibodies (McAb) against six main respiratory tract viruses(RTV)--respiratory syncytial virus (RSV), Influenza A virus (FluA), influenza B virus(FluB), parainfluenza virus type 1.2.3 (PIV1.2.3) were developed, and were used in APAAP bridge-enzyme assay to rapidly detect the antigens of RTV. Total 260 samples of nasopharyngeal exfoliated cells were collected from young men in Beijing Army suffered from respiratory tract virus infections. The results showed that 18 cases were tested with FluA antigen; 10 with PIV2 antigen and 1 with FluB and another with RSV antigen, respectively. All the positive samples were determined by indirect immunofluorescence assay (IFA) and blocking test and replacement test. It is suggested that the method used in the study be effective in clinical rapid diagnosis and epidemiological survey.

Adult↗

PubMed1990

[The antimicrobial activity of fluoroquinolone agents against pathogenic organisms in respiratory tract infections and its clinical effect].

The efficacy rate, minimal inhibitory concentrations (MICs), and resistance of fluoroquinolone agents against causative organisms in respiratory tract infections from January to March, 1988 were investigated. Of 333 pathogenic strains 85% consisted of 5 major causative organisms of respiratory tract infection (Haemophilus influenzae, Pseudomonas aeruginosa, Streptococcus pneumoniae, Branhamella catarrhalis, and Staphylococcus aureus). In 61 (59 cases) of these 333 strains, including 3 cases of acute pharyngitis, 5 of acute bronchitis, 3 of pneumonia, and 48 of chronic lower respiratory tract infection fluoroquinolone agents were administered. The efficacy rate was 76.3% in all cases, and 75% in cases with chronic lower respiratory tract infection. The fluoroquinolone agents were 100% effective in H. influenzae and B. catarrhalis, though the efficacy rate was 67% in S. aureus and 40% in P. aeruginosa. The susceptibility of all strains to fluoroquinolone agents were investigated. There was no resistant strain in H. influenzae and B. catarrhalis, though resistant strains to fluoroquinolone agents have increased in S. aureus and P. aeruginosa. The efficacy rate was investigated using the MIC of administered fluoroquinolone agent against causative organisms. It is surmised that the efficacy of that agent has an MIC of 1.56-3.13 micrograms/ml.

Anti-Bacterial Agents↗

PubMed1986

A comparative study of cefadroxil and co-trimoxazole in patients with lower respiratory tract infections.

The most common causative pathogens in lower respiratory disease are S. pneumoniae, H. influenzae and S. pyogenes. Cefadroxil and co-trimoxazole, both orally administered broad spectrum antibiotics, are effective against these organisms when given in a twice-daily regimen. In this open randomised study, 42 patients with lower respiratory tract infections received cefadroxil 1 g or co-trimoxazole 1 double-strength tablet every 12 hours for a mean duration of 11 and 13 days, respectively. Pathogens were isolated in the pre-treatment sputum of 51% of patients given cefadroxil and in 25% of those who received co-trimoxazole. Similar overall cure rates were observed after treatment with cefadroxil (67%) and co-trimoxazole (60%); sputum purulence was similarly diminished by both drugs (91% and 85%, respectively). Neither antibiotic caused serious side effects. Thus, in a convenient twice-daily regimen, cefadroxil and co-trimoxazole are comparably effective in treating lower respiratory tract infections.

Cefadroxil↗

PubMed1995

Interaction of fimbriated and nonfimbriated strains of unencapsulated Haemophilus influenzae with human respiratory tract mucus in vitro.

Adherence to mucus may influence bacterial colonization of the respiratory tract. Clinical isolates of nontypable Haemophilus influenzae (NTHi) from the respiratory tract are often fimbriated. We wondered whether fimbriated strains have a different adherence from related nonfimbriated strains. A microtitre plate assay has been developed to study adherence of nontypable H. influenzae to mucus. Wells were coated by incubation either with sol phase of sterile mucoid secretions or with purified preparations of mucins. Two laboratory pairs of fimbriated (F+) and nonfimbriated (F-) nontypable H. influenzae, and six fresh clinical isolates of fimbriated nontypable H. influenzae each with nonfimbriated partners derived by serial passage on agar, were cultured to mid-log phase, washed, and then added to the wells. They were then incubated at 37 degrees C for 30 min before washing to remove unbound bacteria. Adherent bacteria were desorbed by agitation with 0.5% Tween 80 and a viable count performed. The two fimbriated laboratory strains (n = 12 and n = 17), and 5 of the 6 fimbriated clinical isolates were more adherent to sol phase than their respective nonfimbriated partners. Two nonfimbriated clinical isolates were more adherent to plastic than their fimbriated partners. A fimbriated laboratory strain was more adherent than its nonfimbriated partner both to a purified preparation of high molecular mass mucin and to the glycopeptide fraction of the same. We conclude that fimbriated strains of nontypable H. influenzae have increased adherence to sol phase of mucus and purified human respiratory tract mucin. The interactions of fimbriae with mucus are likely to be complex, and may involve both nonspecific and specific interactions.

Bacterial Adhesion↗

PubMed1990

Aerosols for delivery of therapeutic and diagnostic agents to the respiratory tract.

Inhaled therapeutic and diagnostic aerosols are examples of targeted delivery systems: they achieve high concentration in the respiratory tract (the usual target organ with these systems) while appearing in low concentrations in other parts of the human body. Development and use of inhalation aerosols requires an appreciation of the properties of these dynamic systems and the ways in which they interact with the anatomically and pathophysiologically complex human respiratory tract. The amounts of aerosol particles, or droplets, initially deposited at various sites in the respiratory tract will determine the intensity of local effects as well as the rate of clearance of these materials from the respiratory lumen. This activity can be modulated by suitable formulation intervention, such as presentation of the active agent in a slow releasing form carrier. Extension of duration of action of inhaled drugs by such means could be possible. As more discriminating methods for location of receptors and for the following of the fate of inhaled drugs and their carriers are becoming available, the ultimate potential for improvement of selective toxicity of agents used in pulmonary therapy by direct delivery into the respiratory tract can be critically evaluated.

Aerosols↗

PubMed1988

Does de novo immunoglobulin synthesis occur on the epithelial surface of the human lower respiratory tract?

Although synthesis of immunoglobulins by cells in the human lower respiratory tract has never been directly demonstrated, local production of immunoglobulins by cells within lung parenchyma is thought to play an important role in protecting the normal human lung against a variety of pathogenic organisms, and may contribute to the development of some interstitial lung diseases. To determine whether or not the epithelial surface of the human lower respiratory tract is a site of immunoglobulin synthesis, immunoglobulin production by cells recovered by bronchoalveolar lavage and lung parenchymal tissue from normal subjects and patients with idiopathic pulmonary fibrosis (IPF) or sarcoidosis was evaluated using a reverse hemolytic plaque assay and by measuring incorporation of [35S]methionine into immunoglobulins. Although the reverse hemolytic plaque assay demonstrated immunoglobin-releasing cells to be present on the surface of the lower respiratory tract of normal subjects, and present in increased numbers in patients with IPF or sarcoidosis, these plaque-forming cells were not actively synthesizing immunoglobulins, since preincubation of lavage cells in order to remove immunoglobulin bound to the surface of the cells reduced the number of plaque-forming cells, and inhibition of protein synthesis by cycloheximide did not further reduce the number of plaque-forming cells. Furthermore, direct evaluation of immunoglobulin synthesis using radiolabeling, immunoprecipitation and SDS-polyacrylamide gel electrophoresis failed to detect de novo IgG production by cells recovered from the alveolar surface of 15 of 17 subjects, IgM by 17 of 17, and IgA by 16 of 17.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMedDate not supplied

Acute lower respiratory tract infections in hospitalized patients with diarrhea in Dhaka, Bangladesh.

This study focused on 401 children less than 5 years old who were hospitalized with acute lower respiratory tract infection (ALRI) and diarrhea in Dhaka, Bangladesh, and who were investigated for the presence of both bacterial and viral respiratory tract pathogens as well as for selected diarrheal pathogens. The most common manifestations of ALRI were pneumonia (374 cases), bronchiolitis (12 cases), and tracheobronchitis (11 cases). The majority (77%) of the illnesses were in children less than 2 years of age, and 88% of the children were malnourished. A respiratory tract pathogen was identified in 30% of the patients, and a diarrheal pathogen was identified in 34%. The overall case-fatality rate in children with ALRI and diarrhea was 8%. The case-fatality rate was 14% in children with bacterial pneumonia and diarrhea, 3% in those with viral pneumonia and diarrhea, and 14% in malnourished children with shigellosis and ALRI. The most common respiratory tract pathogens were respiratory syncytial virus, Streptococcus pneumoniae, influenza viruses, and Haemophilus influenzae type b.

Acute Disease↗

PubMed2005

Distribution of leucocyte subsets in the canine respiratory tract.

Histochemistry and immunohistochemistry were used to characterize leucocyte subsets in the respiratory tract of 15 outbred dogs (five aged <6 months and 10 aged >1 year) that had no evidence of respiratory disease. No organized nose- or bronchus-associated lymphoid tissue was observed in any of the sections examined. IgA(+) plasma cells predominated in nasal mucosa and in all parts of the bronchial tree, with fewer IgG(+) and IgM(+) plasma cells. The numbers of IgA(+) and IgM(+) cells were significantly greater in the nasal mucosa than in any other part of the respiratory mucosa. There were significantly fewer IgA(+), IgG(+) and IgM(+) cells in all parts of the respiratory tract in the puppies than in the adults. The number and distribution of mast cells and cells expressing MHC class II, L1 or CD1c were recorded. Mast cells were mainly found in the subepithelial lamina propria of nasal and bronchial mucosa and in the alveolar interstitium, and cells expressing IgE had a similar distribution. Mast cells were also present within muscle layers of the bronchial tree. The numbers of mast cells and MHC class II(+) cells were significantly greater in the nasal mucosa than in any other part of the respiratory mucosa. In the nose, carina and primary and secondary bronchus, there were significantly more mast cells and MHC class II(+) cells in puppies than in adult dogs, whereas the numbers of L1(+) cells and CD1c(+) cells in most sites were significantly greater in older dogs. There were significantly more CD3(+) and CD8(+) cells in the nasal mucosa than in any part of the bronchial mucosa. In most parts of the respiratory mucosa, CD4(+), CD8(+) and TCR alphabeta(+) cells were present in significantly greater numbers in adults than in puppies. All parts of the respiratory tract had similar numbers of mucosal CD4(+) and CD8(+) T lymphocytes. TCR gammadelta(+) cells were absent or sparse in all samples. These data, obtained from dogs without respiratory disease, will enable comparisons to be made with dogs suffering from infectious or inflammatory nasal, bronchial and pulmonary diseases.

Animals↗

PubMed2000

Novel lipid-based hollow-porous microparticles as a platform for immunoglobulin delivery to the respiratory tract.

PURPOSE: Delivery of specific antibodies or immunoglobulin constructs to the respiratory tract may be useful for prophylaxis or active treatment of local or systemic disorders. Therefore, we evaluated the utility of lipid-based hollow-porous microparticles (PulmoSpheres) as a potential delivery vehicle for immunoglobulins. METHODS: Lipid-based microparticles loaded with human immunoglobulin (hIgG) or control peptide were synthesized by spray drying and tested for: i) the kinetics of peptide/protein release, using ELISA and bioassays; ii) bioavailability subsequent to nonaqueous liquid instillation into the respiratory tract of BALB/c mice, using ELISA and Western blotting; iii) bioactivity in terms of murine immune response to xenotypic epitopes on human IgG, using ELISA and T cell assays; and iv) mechanisms responsible for the observed enhancement of immune responses, using measurement of antibodies as well as tagged probes. RESULTS: Human IgG and the control peptide were both readily released from the hollow-porous microspheres once added to an aqueous environment, although the kinetics depended on the compound. Nonaqueous liquid instillation of hIgG formulated in PulmoSpheres into the upper and lower respiratory tract of BALB/c mice resulted in systemic biodistribution. The formulated human IgG triggered enhanced local and systemic immune responses against xenotypic epitopes and was associated with receptor-mediated loading of alveolar macrophages. CONCLUSIONS: Formulation of immunoglobulins in hollow-porous microparticles is compatible with local and systemic delivery via the respiratory mucosa and may be used as means to trigger or modulate immune responses.

Administration, Inhalation↗

PubMed2007

Significance of human beta-defensins in the epithelial lining fluid of patients with chronic lower respiratory tract infections.

Human beta-defensins (hBDs) are the most abundant antimicrobial peptides in epithelial cells, and function in the host immune system. Respiratory epithelial cells express hBDs to inhibit bacterial proliferation during respiratory tract infections. The aim of this study was to investigate the release of hBDs into the respiratory tract and their benefit as a host defence system in chronic Pseudomonas aeruginosa infections. The levels of four hBD peptides (hBD-1-hBD-4) were measured in the bronchial epithelial lining fluid (ELF) of nine patients with chronic lower respiratory tract infection caused by P. aeruginosa. Eight patients with idiopathic pulmonary fibrosis and eight volunteers free of pulmonary disease were recruited as controls. ELF was obtained by bronchoscopic microsampling and hBD levels were measured by radioimmunoassays. The antimicrobial effects of hBDs were studied individually and in combination using an in-vitro colony count assay for P. aeruginosa. Concentrations of hBD-1 and hBD-3 tended to be higher in patients with chronic lower respiratory tract infection than in the controls. hBD-2 and hBD-4 were detected in ELF from five and four of nine patients, respectively, but the hBD levels in controls were all below the limits of detection. All patients with infection caused by mucoid P. aeruginosa had detectable hBD-2 and hBD-4 levels in ELF. In-vitro colony count assays showed a potential synergism between hBD-2 and hBD-4 in inhibiting bacterial proliferation. The findings indicate that hBDs, especially hBD-2 and hBD-4, are pathophysiologically important in infections caused by mucoid strains of P. aeruginosa.

Aged↗

PubMed1997

Effect of rapid viral diagnosis on the management of children hospitalized with lower respiratory tract infection.

BACKGROUND: Although rapid viral tests are commonly used in children with lower respiratory tract infection, their effect on patient management has not been studied. OBJECTIVES: To examine how physicians utilize an enzyme immunoassay for respiratory syncytial virus (RSV EIA) and a centrifugation-enhanced cellular immunofluorescence assay for multiple viral pathogens [viral respiratory panel (VRP)] in children hospitalized with respiratory illness; to determine the effect of testing on length of stay, antibiotic use and costs; and to determine physician attitudes toward RSV testing. DESIGN AND SETTING: Prospective study and survey at a large children's hospital. PATIENTS: Previously healthy children < 24 months of age consecutively admitted between January 1 and February 11, 1995, with symptoms of lower respiratory tract infection. RESULTS: Of 200 patients 160 were tested by RSV EIA; 92 were positive and 68 were negative. Tested children were younger, more tachypneic and more likely to require oxygen than those not tested. Overall the length of stay was similar in RSV-positive and -negative patients. Although equal proportions of each group were given antibiotic therapy, RSV-positive children received antibiotic therapy for fewer days than RSV-negative children (median 2 vs. 3 days; P = 0.0387). However, a crude cost analysis did not support a strategy of testing all bronchiolitis patients for RSV. Sixty-five of the 68 RSV-negative children were tested for RSV and other pathogens by VRP. In 55 cases the results were not available until after patient discharge and could not have influenced their management. One hundred three physicians caring for children in the study were surveyed. Of 75 respondents almost all thought that RSV EIA results influenced their management of patients and were important to parents. CONCLUSIONS: Most children hospitalized with symptoms of lower respiratory tract infection were tested for viral pathogens. The VRP provided little clinically useful information. In contrast RSV EIA results may have been used by clinicians to make antibiotic decisions. Physicians felt that rapid testing for RSV was important.

Anti-Bacterial Agents↗

PubMed1999

Alveolar macrophages of children suffering from recurrent infections of respiratory tract are less efficient in eliminating apoptotic neutrophils.

During bacterial infections of the respiratory tract, neutrophils (PMN) are recruited to the lung by various mechanisms, including production of interleukin-8 (IL-8) by alveolar macrophages (AM). After fulfilling their defense function, PMN become apoptotic and have to be disposed of by AM to prevent local damage to the lung tissue by oxygen species and proteolytic enzymes. We measured the levels of IL-8 in the bronchoalveolar lavage (BAL) and the ability of AM to engulf senescent PMN in a groups of children with and without recurrent infections of the respiratory tract. The IL-8 level was measured by enzyme-linked immunosorbent assay (ELISA). The phagocytosis of apoptotic neutrophils was evaluated microscopically by the presence of myeloperoxidase positive material in AM before and after 1 h of incubation with senescent PMN. The data show that children suffering from recurrent infections have increased IL-8 in BAL and that their AM have a lower ability to engulf apoptotic PMN in vitro. Furthermore, the proportion of annexin V-binding cells was higher in BAL of children with recurrent infections of the respiratory tract than in normal controls.

Adolescent↗