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The role of group C and group G streptococci in acute pharyngitis in children.

Group C streptococci (GCS) and group G beta-haemolytic streptococci (GGS) have caused well-documented epidemics of acute pharyngitis in children, but the importance of these organisms in causing endemic or sporadic pharyngitis is uncertain. The heterogeneity of GCS and GGS may obscure the role of certain subtypes, such as the large-colony-forming strains of group C (Streptococcus dysgalactiae subsp. equisimilis) or group G, in endemic pharyngitis. For a 1-year period, children (aged 6 months to 18 years) (n = 2085) who presented with pharyngitis to the children's hospital emergency department and two outpatient offices were enrolled in a cross-sectional study to ascertain the role of large-colony-forming GCS and GGS in acute pharyngitis. Control patients (n = 194) were children who presented to the same locations during the same time period with non-respiratory tract symptoms or to the orthopaedic cast clinic. Throat cultures were obtained by a standard reference method, and swabs were plated on Strep-Selective Agar. Lancefield grouping and species identification was performed on all beta-haemolytic isolates. In total, 65 (3%) large-colony-forming GCS and GGS strains were obtained from pharyngitis patients, and three (1.5%) were obtained from the control group (odds ratio 2.0; 95% confidence interval 0.6-6.1). The low isolation rate of large-colony-forming strains of GCS and GGS indicates that even if these organisms are associated with acute, sporadic pharyngitis in paediatric patients, they represent an unusual pathogen.

Acute Disease↗

Effect of sodium azulene sulfonate on capsaicin-induced pharyngitis in rats.

Sodium azulene sulfonate is a water-soluble derivative of azulene which is an antiinflammatory component of chamomile of the family of Asteraceae. Sodium azulene sulfonate is clinically used as a therapeutic agent in the treatment of pharyngitis as well as other inflammatory diseases such as tonsillitis, stomatitis and conjunctivitis. There has been no documentation on the effect of sodium azulene sulfonate on pharyngitis in laboratory models, probably because of no availability of such models. We recently established a pharyngitis model using capsaicin application on pharyngeal mucosa in rats. The present study investigated the antipharyngitis activity of sodium azulene sulfonate comparing with those of ruthenium red (vanilloid receptor antagonist, 8.5 and 85 mg/ml), ascorbic acid (antioxidative compound, 100 microg/ml), povidone iodine (gargle as disinfectant, oxidative compound, 5 and 20 mg/ml) and diclofenac sodium (cyclooxygenase inhibitor, 0.1 and 1 mg/ml). As an antipharyngeal effect, the capsaicin-induced plasma exudation in the pharyngeal mucosa of the rat was evaluated. The capsaicin-induced plasma exudation in the pharyngeal mucosa was inhibited by sodium azulene sulfonate (100 and 200 microg/ml) as well as ruthenium red and ascorbic acid, but not by povidone iodine and dicrofenac sodium; povidone iodine rather promoted the plasma exudation. In conclusion, the antipharyngitis effect of sodium azulene sulfonate was demonstrated for the first time in a laboratory model. Although the mechanism by which sodium azulene sulfonate inhibited the capsaicin-induced pharyngitis is not yet unraveled, antioxidative effect, but not inhibitory effect on cyclooxygenase pathway, might be involved.

Animals↗

Pharyngeal lymphoid hyperplasia in Thoroughbred racehorses in training.

The prevalence of pharyngeal lymphoid hyperplasia in Thoroughbred racehorses in training was investigated using a fibre optic endoscope. Of the 70 horses examined, all but 8 showed evidence of pharyngeal lymphoid hyperplasia and the severity of the pharyngeal changes decreased with age. Two-year old horses had greater pharyngeal lymphoid hyperplasia (p less than 0.05) when compared to all other age groups. More horses (p less than 0.05) with Grade 3 or Grade 4 pharyngeal lymphoid hyperplasia experienced recent mild respiratory disease than did horses with Grade 2 or less pharyngeal lymphoid hyperplasia. None of the horses examined had a history of diminished racing performance although 30% had either Grade 3 or Grade 4 pharyngeal lymphoid hyperplasia.

Age Factors↗

Epidemiologic evidence for Lancefield group C beta-hemolytic streptococci as a cause of exudative pharyngitis in college students.

The isolation rates of strains of group C beta-hemolytic streptococci from throat swab cultures of patients with exudative pharyngitis, the common cold, and healthy controls were compared. By using a cohort study design in a college health service, patients with exudative pharyngitis were retrospectively identified by description of tonsillar exudate on chart review. Patients with rhinoviral infection were prospectively identified during a common cold study. Healthy controls were prospectively recruited from patients presenting with noninfectious conditions. Isolation of Lancefield group A and C beta-hemolytic streptococci from throat cultures was used as an outcome measurement. A total of 265 students (62% female; average age 20.2 years) with exudative pharyngitis were identified. A total of 75 students (60% female; average age, 21.7 years) from a common cold study with rhinoviral infection were identified. A total of 162 students (53% female; average age, 22.6 years) were recruited as healthy controls. Group A beta-hemolytic streptococci were isolated from 5% of patients with pharyngitis but none of those with rhinovirus (P = 0.045) and none of the controls (P = 0.007). Group C Streptococcus dysglactiae subsp. equisimilis was isolated from 11% of patients with pharyngitis but none of those with rhinovirus (P = 0.006) and 2% of controls (P = 0.001). Lancefield group C Streptococcus anginosus was isolated from 8% of patients with pharyngitis but 3% of those with rhinovirus (P = 0.18) and 1% of controls (P = 0.006). Heavier growth of colonies on the primary culture plate was observed for patients from whom S. equisimilis and group A beta-hemolytic streptococci were isolated. Lancefield group C beta-hemolytic streptococci appear to be associated with exudative pharyngitis in college students.

Adult↗

Evaluation of ligase chain reaction for the non-cultural detection of rectal and pharyngeal gonorrhoea in men who have sex with men.

OBJECTIVES: To compare a nucleic acid amplification test (ligase chain reaction) with culture for detecting rectal and pharyngeal gonorrhoea in men who have sex with men (MSM). METHODS: Duplicate rectal and throat swabs from MSM attending a genitourinary medicine clinic were collected for culture on modified New York City medium and detection of gonococcal nucleic acid by the Abbott ligase chain reaction (LCR) utilising probes based on opa 1 gene sequences. LCR positive culture negative specimens were tested by a second LCR utilising probes based on pilin gene sequences. Patients with rectal and/or pharyngeal cultures yielding Gram negative diplococci confirmed as Neisseria gonorrhoeae by biochemical and immunological methods were diagnosed with rectal and/or pharyngeal gonorrhoea. The criteria for diagnosing rectal and pharyngeal infection by LCR included a positive opa LCR with a positive culture from the same site or, in the case of a negative culture, a positive opa LCR and a positive pilin LCR. RESULTS: Duplicate rectal samples were obtained from 227 MSM. The results of LCR and culture were concordant in 219 samples (96.5%). The prevalence of rectal gonorrhoea by LCR and culture was 7.0% (16/227) and 4.0% (9/227), respectively. Duplicate throat samples were obtained from 251 MSM. The results of LCR and culture were concordant in 230 (91.6%) cases. The prevalence of pharyngeal gonorrhoea by LCR and culture was 12.7% (32/251) and 6.0% (15/251), respectively. The specificity of LCR was 99.5% (210/211) for rectal and 98.2% (215/219) for pharyngeal specimens. CONCLUSIONS: The high prevalence and asymptomatic nature of pharyngeal and rectal gonococcal infection suggests that routine screening for infection at these sites by a nucleic acid amplification test method such as LCR should be considered as part of the overall strategy to control gonorrhoea in MSM.

Gonorrhea↗

Inferior pharyngeal constrictor electromyographic activity during permeability pulmonary edema in lambs.

Newborn mammals exhibit an active expiratory upper airway closure during the first hours of extrauterine life. We have recently shown that permeability pulmonary edema led to active expiratory glottic closure in awake newborn lambs while hypoxia (inspired O2 fraction 8%; 15 min) did not. In the present study, we tested the hypothesis that expiratory glottic closure was accompanied by an increase in pharyngeal constrictor muscle expiratory electromyographic (EMG) activity. We studied seven awake nonsedated lambs aged 8-20 days. Airflow (facial mask + pneumotachograph), blood gases (arterial catheter), and EMG activity of both the thyroarytenoid muscle (a glottic adductor) and the inferior pharyngeal constrictor muscle were recorded before and after intravenous injection of halothane (0.05 ml/kg) to induce a permeability pulmonary edema. A central apnea (duration 15 s to 5 min) with continuous thyroarytenoid and inferior pharyngeal constrictor activity was observed within seconds after halothane injection. One lamb died despite rescuing maneuvers. An expiratory phasic thyroarytenoid and inferior pharyngeal constrictor muscle activity with simultaneous zero airflow gradually took place and, by 30 min after halothane injection, was present at each expiration in the six remaining lambs. Expiratory glottic and pharyngeal constrictor muscle EMG activity was subsequently present during the whole study period (1.5-5 h), even after correction of the initial hypoxia. Permeability lung edema was present at postmortem examination in all seven lambs. We conclude that a permeability pulmonary edema induced by intravenous halothane in non-sedated lambs enhances both glottic and pharyngeal constrictor muscle expiratory EMG. We hypothesize that expiratory contraction of the inferior pharyngeal constrictor muscle could participate in the active expiratory upper airway closure; this, in turn, might improve alveolocapillary gas exchange by increasing the end-expiratory lung volume.

Anesthetics, General↗

Oral and pharyngeal reflexes in the mammalian nervous system: their diverse range in complexity and the pivotal role of the tongue.

The oral cavity and pharynx are anatomically separate but functionally integrated regions of the head. The two regions are involved in complex motor responses that include feeding, chewing, swallowing, speech, and respiration. The multiple sensory receptors that innervate these two regions provide the first link in reflexes that control muscles of the entire head, upper gastrointestinal tract, and airway. Most of the reflexes affect the diversity of muscles that compose the tongue, which is vital to all stages of feeding and which continually affects the patency of the airway. Oral-pharyngeal reflexes are evident in the mammalian fetus and continually emerge as the animal or human matures. Some of the first reflexes in the oral region are geared toward nourishment. As the central nervous system matures and the oral and pharyngeal regions develop morphologically, new reflexes develop. Many of these reflexes are protective both of the tissue in the oral cavity, such as the tongue, and of the upper airway in preventing aspiration. While simple reflexes can be evoked in isolation, most reflexes combine with more complex oral and pharyngeal responses such as chewing and vocalization. Oral-pharyngeal reflexes demonstrate a range in complexity. Some sensory stimuli will evoke a series of responses, as is often evident in the infant, and other stimuli will evoke a complex multiple-level recruitment of muscles in a sequence, as in pharyngeal swallowing. Certain sensory inputs evoke an entire motor behavior pattern, such as taste avoidance or facial expression. The oral-pharyngeal reflexes are critical to maintaining life and ultimately serve functions that the oral and pharyngeal regions have in common, such as communication, feeding, and breathing.

Animals↗

Serotonin regulates repolarization of the C. elegans pharyngeal muscle.

Caenorhabditis elegans feeds by rhythmically contracting its pharynx to ingest bacteria. The rate of pharyngeal contraction is increased by serotonin and suppressed by octopamine. Using an electrophysiological assay, we show that serotonin and octopamine regulate two additional aspects of pharyngeal behavior. Serotonin decreases the duration of the pharyngeal action potential and enhances activity of the pharyngeal M3 motor neurons. Gramine, a competitive serotonin antagonist, and octopamine have effects opposite to those of serotonin: gramine and octopamine increase action potential duration and suppress M3 activity. The effects of serotonin, gramine and octopamine on action potential duration are dependent on the pharyngeal motor neurons MC and M3. When the MC and M3 motor neurons are functionally defective, serotonin and octopamine do not regulate the action potential. Our data suggest that serotonin alters pharyngeal physiology to allow for rapid contraction-relaxation cycles. Reciprocal regulation of pharyngeal behavior by serotonin and octopamine provides a mechanism for adapting to the presence and absence of food, respectively.

Action Potentials↗

Spectrum bias of a rapid antigen detection test for group A beta-hemolytic streptococcal pharyngitis in a pediatric population.

BACKGROUND: Rapid antigen detection testing (RADT) is often performed for diagnosis of group A beta-hemolytic streptococcal (GABHS) pharyngitis among children. Among adults, the sensitivity of this test varies on the basis of disease severity (spectrum bias). A similar phenomenon may occur when this test is used in a pediatric population, which may affect the need for culture confirmation of all negative RADT results. OBJECTIVES: To assess the performance of a clinical scoring system and to determine whether RADT spectrum bias is present among children who are evaluated for GABHS pharyngitis. METHODS: Laboratory and clinical records for a consecutive series of pediatric patients who underwent RADT at the Marshfield Clinic between January 2002 and March 2002 were reviewed retrospectively. Patients were stratified according to the number of clinical features present by using modified Centor criteria, ie, history of fever, absence of cough, presence of pharyngeal exudates, and cervical lymphadenopathy. The sensitivity of the RADT was defined as the number of patients with positive RADT results divided by the number of patients with either positive RADT results or negative RADT results but positive throat culture results. RESULTS: RADT results were positive for 117 of 561 children (21%), and culture results were positive for 35 of 444 children (8%) with negative RADT results. The overall prevalence of GABHS pharyngitis was 27% (95% confidence interval: 23-31%). The prevalence of GABHS pharyngitis was 18% among patients with 0 Centor criteria, 16% among those with 1 criterion, 32% among those with 2 criteria, and 50% among those with 3 or 4 criteria. Spectrum bias was present, inasmuch as RADT sensitivity increased with Centor scores, ie, 47% sensitivity among children with 0 Centor criteria, 65% among those with 1 criterion, 82% among those with 2 criteria, and 90% among those with 3 or 4 criteria. CONCLUSIONS: The sensitivity of RADT for GABHS pharyngitis is not a fixed value but varies with the severity of disease. However, even among pediatric patients with > or =3 Centor criteria for GABHS pharyngitis, the sensitivity of RADT is still too low to support the use of RADT without culture confirmation of negative results.

Adolescent↗

[Value of a rapid test for identification of beta-hemolytic streptococcus antigens in children with streptococcal pharyngitis].

Beta-hemolytic group A streptococcus (Streptococcus pyogenes) is the most common bacterial agent associated with the upper respiratory tract infections in humans. The most frequently group A streptococcus-associated disease is pharyngitis. Males and females are equally affected by group A streptococcus. There is seasonal increase in the prevalence of group A streptococcus-associated pharyngitis. Streptococcal pharyngitis is most prevalent in winter and early spring with higher incidence of disease observed in crowded population such as school children. Early diagnosis and treatment of group A streptococcal pharyngitis has been shown to reduce the severity of symptoms and further complications such as rheumatic fever and glomerulonephritis. The conventional methods used for identification of group A streptococci depend on isolation and identification of the organism on blood agar plates. These methods usually require 18-24 hours of incubation at 37 degrees C. Such delay in identifying the group A streptococcus has often made physicians to administer therapy without first disclosing the etiological agent. Development of immunologic tests, capable of detecting the group A streptococcal antigen directly from the throat swabs, produced rapid test results employed for better treatment of patients. STREP A test is a rapid immunochromatographic test for the detection of group A streptococci from throat swabs or culture. The accuracy of the test does not depend on the organism viability. Instead, group A strep antigen is extracted directly from the swab and identified using antibodies specific for the group A carbohydrates. We compared rapid test with conventional throat swab in 40 children, who met Centor criteria for streptococcal pharyngitis (absence of cough, high fever, purulent pharyngitis, enlarged and painful cervica lymph nodes). Overall congruence of rapid test and culture was 94%. Test is easy to perform and it is recommended as the first diagnostic test for management of children with streptococcal pharyngitis. In children with negative test, but with characteristics highly suggestive of streptococcal infection, throat culture should be performed.

Adolescent↗

Helicobacter pylori infection in the pharynx of patients with chronic pharyngitis detected with TDI-FP and modified Giemsa stain.

AIM: To detect whether there is Helicobacter pylori (H pylori) colonization in the pharynx mucous membrane of healthy people and whether chronic pharyngitis is related to H pylori infection. METHODS: Fifty cases of chronic pharyngitis refractory over three months were prospectively studied from March 2004 to August 2004 in the otolaryngology outpatient department of the Second Hospital of Xi'an Jiaotong University. Template-directed dye-terminator incorporated with fluorescence polarization detection (TDI-FP) and modified Giemsa stain were used to examine pharynx mucous membrane tissue for H pylori colonization in the patients with chronic pharyngitis and the healthy people as a control group. RESULTS: In the control group, no people were detected to have H pylori in the pharynx. In contrast, in 50 cases with chronic pharyngitis, 19 (38.0%) cases were H pylori positive with a TDI-FP assay and 4 (8%) cases were TDI-FP positive with Giemsa staining in the pharynx. Sixteen of the 50 pharyngitis cases had stomach ailment history, 11 cases (68.8%) of these 16 patients were determined to be H pylori positive in the pharynx with the TDI-FP assay. c2 test showed that this infection rate was remarkably higher (P=0.0007) than that in the cases without stomach ailment history. Giemsa staining showed that 3 cases (18.8%) of the patients with stomach ailment history were infected with H pylori in the pharynx, which was remarkably higher (P=0.042) than that in the patients without stomach ailment history (1 case, which was 2.9%). CONCLUSION: H pylori may not be detected in the pharynx of healthy people. Chronic pharyngitis may be related to H pylori infection. The infection rate with H pylori in the pharynx is higher in patients with stomach ailment histories than in patients without stomach ailment histories, suggesting that chronic pharyngitis may be related to stomach ailment history.

Adult↗

The burden of group A streptococcal pharyngitis in Melbourne families.

BACKGROUND & OBJECTIVES: There are no recent data from industrialised countries documenting the incidence and costs of group A streptococcal (GAS) pharyngitis. Such data are important in developing policy regarding management (e.g., whether or not to use antibiotics to treat sore throat) and in planning preventive strategies, including preparing for the arrival of GAS vaccines. The present study was undertaken to estimate the incidence and costs of GAS pharyngitis in school aged children in Melbourne, Australia. We report here the results after initial 11 months of surveillance. METHODS: A total of 202 families (852 individuals) with at least one child aged 3 to 12 yr were enrolled across Melbourne in a family-based cohort study, and are being followed prospectively for 24 months. Surveillance data for acute GAS pharyngitis (including serology), throat carriage, and costs of the disease were collected. Additional cases of GAS pharyngitis have been ascertained to improve the precision of costing estimates. RESULTS: Cohort retention was 97 per cent. The spring, summer and winter carriage rates for children were 13.0, 8.0 and 16.0 per cent respectively. The incidence of GAS pharyngitis was 14 per 100 person-years for children. For every primary case there were 0.7 secondary cases and 24 per cent of families experienced at least one episode of GAS pharyngitis per year. Preliminary costing data suggest that 46 per cent of cases lead to school absenteeism and a high rate of antibiotic use. INTERPRETATION & CONCLUSION: The present data suggest that GAS pharyngitis remains very common in childhood, and that it has further implications in terms of secondary cases and costs.

Cohort Studies↗

Manometric and radionuclide assessment of pharyngeal emptying before and after cricopharyngeal myotomy in patients with oculopharyngeal muscular dystrophy.

Fifteen patients with oculopharyngeal muscular dystrophy underwent cricopharyngeal myotomy for palliation of dysphagia. The aim of this work was to assess the effectiveness of this operation by using a radionuclide pharyngeal emptying study as a new quantitative method in addition to clinical and manometric evaluation. Radionuclide study was performed with the patient in both the upright and the supine positions after ingestion of 15 ml of water labeled with sulfur colloid 99mTc. Computerized data were acquired at 0.5 second intervals for 15 minutes and a pharyngeal time-activity curve was generated. Four quantitative parameters were evaluated: the time for pharyngeal clearance of 25%, 50%, and 75% of the ingested radioactive water and the pharyngeal stasis at 15 minutes. Manometric studies were also performed before and after cricopharyngeal myotomy. The pharyngeal clearance of 25%, 50%, and 75% of the water and pharyngeal stasis at 15 minutes were all improved by cricopharyngeal myotomy, decreasing from 1.2 to 0.9 second (p less than 0.04), 4.2 to 2 seconds (p less than 0.005), 15 to 7 seconds (p less than 0.02), and 10.3% to 6% (p less than 0.01), respectively. Both pharyngoesophageal and tracheobronchial symptoms were also significantly improved by cricopharyngeal myotomy. Manometric evaluation showed a decrease of the upper esophageal sphincter closing pressure from 60.1 mm Hg before to 28.2 mm Hg after the operation (p less than 0.001), and the resting pressure decreased from 34.4 to 15.7 mm Hg (p less than 0.0005). Cricopharyngeal myotomy significantly improves both symptoms and pharyngeal emptying in patients with oculopharyngeal muscular dystrophy.

Aged↗

Screening for pharyngeal gonorrhea in the urban teenager.

A retrospective chart review assessed the occurrence of pharyngeal gonorrhea among 546 teenagers who attended a general adolescent clinic and were cultured for gonorrhea; they had been routinely cultured at three sites (cervix/urethra, rectum, and pharynx) regardless of their history of sexual practice. No record of specific sexual practice was available. This population was predominantly urban, black, and female; the age range was 11 to 22 years (mean = 16.5). The overall occurrence of gonorrhea was 14.7% (80/546). Pharyngeal gonorrhea was detected in 2.7% of the study population, representing 12 females and three males. Of the 80 patients with gonorrhea, 15% had only pharyngeal gonorrhea. History was available for 13/15 patients none had pharyngeal symptoms. Approximately half were detected by routine screening at a family planning visit; the remainder had complaints related to sexually transmitted disease. The occurrence of pharyngeal gonorrhea is sufficiently high to merit study of the indications for pharyngeal culture of teenaged patients. Given the potential for disseminated infection and absence of information regarding the reliability of self-report, it currently appears appropriate to culture adolescents routinely for pharyngeal gonorrhea, regardless of stated sexual practice, whenever genital cultures are collected.

Adolescent↗

Group B streptococcal pharyngitis in the compromised adult: therapeutic considerations.

Group B streptococci (GBS) have been infrequently recognized as a cause of pharyngitis. We report three cases of GBS pharyngitis in patients with underlying diseases, two of whom were treated with and responded incompletely to oral beta-lactam antibiotics. The susceptibility of 20 clinical isolates of GBS was tested by a broth dilution method to six antibiotics which could conceivably be used in the therapy of GBS pharyngitis. Penicillin G, clindamycin, and erythromycin were most active with mean minimal inhibitory concentrations (MIC) of 0.06 μg/ml or less. Rifampin and cefaclor were least active with mean MICs of 0.71 ug/ml or more. Ampicillin was intermediate in its activity. Therapy traditionally used for Group A streptococcal (GAS) pharyngitis may, at times, be suboptimal for GBS pharyngitis in compromised patients. This may be due to higher minimal bactericidal concentrations (MBC) of GBS than GAS, to inadequate penetration of penicillins into pharyngeal tissues or to host factors. It is suggested that GBS can cause pharyngitis in adults, particularly the compromised patient, and that in cases where there is a poor response to penicillin or ampicillin therapy, alternative drugs (erythromycin or clindamycin) may be used.

Adolescent↗

Do gastrointestinal symptoms accompanying sore throat predict streptococcal pharyngitis? An UPRNet study. Upper Peninsula Research Network.

BACKGROUND: The purpose of this study was to determine whether gastrointestinal (GI) symptoms are more common in streptococcal than nonstreptococcal pharyngitis, and, if so, whether these symptoms are useful diagnostic predictors. METHODS: Patients aged 4 and older presenting consecutively to one of three family practice clinics and one emergency department with the chief complaint of sore throat were invited to participate in the study. A nurse administered a brief symptom checklist; after documenting clinical signs, the clinician assessed and treated the patient. All patients were screened for group A streptococcus using the Abbott Test Pack Plus. Patients were enrolled from January 1996 through March 1996. Significant associations of signs and symptoms with streptococcal pharyngitis were determined by chi square, likelihood ratios were calculated, and logistic regression was used to compare diagnostic prediction models with and without GI symptoms. RESULTS: Six hundred fifty-seven consecutive patients with the presenting complaint of sore throat were enrolled in the study. The mean age of the patients enrolled was 19 years; the median age was 14. Thirty-two percent of the children (ages 4 to 18), 23% of the adults (ages 19 to 74), and 29% of all patients had streptococcal pharyngitis. Symptom frequencies for streptococcal and nonstreptococcal pharyngitis, respectively, were: nausea (39% vs 31%, P = .14); vomiting (14% vs 7%, P = .004); abdominal pain (27% vs 26%, P = .621); and any GI symptom (47% vs 41%, P = .45). When included in a predictive model with other significant predictors of streptococcal pharyngitis including age, palatal petechiae, absence of cough, and anterior cervical adenopathy, the addition of nausea or vomiting added slight predictive power to the models, but abdominal pain and "any GI symptom" did not. CONCLUSIONS: Nausea and vomiting are somewhat more common in streptococcal than in nonstreptococcal pharyngitis, but appear to have limited usefulness as clinical predictors of streptococcal pharyngitis.

Adolescent↗

Pharyngeal transport dysfunction consequent to an organ-sparing protocol.

OBJECTIVE: To investigate the effects of a protocol of concomitant intravenous hydroxyurea and hyperfractionated, accelerated, external-beam radiation therapy on the swallowing mechanism of patients with advanced-stage head and neck cancer. DESIGN: Posttreatment videofluoroscopic swallow function studies, using images of single-bolus swallows of low-density liquid barium, were analyzed in real time, slow motion, and frame by frame using an integrated system that allows objective analysis of video recordings through image processing and digitization (Kay Elemetrics Computerized Swallowing Station). Radiological descriptors were used for pharyngeal transport abnormalities, and temporal measures were obtained of structural movements. SETTING: Academic, tertiary care, referral medical center. PATIENTS: Fifteen consecutive patients with previously untreated, stages III and IV, nonmetastatic squamous cell carcinoma of the head and neck who underwent a phase 1 study of prolonged infusion hydroxyurea therapy in combination with hyperfractionated, accelerated external-beam radiation therapy for their disease. RESULTS: All patients had anterior pharyngeal segment dysfunction, characterized by no epiglottic movement and slowed laryngeal motility (1.011 +/- 0.379 seconds [mean +/- SD). Anterior pharyngeal dysfunction was more severe in patients with primary tumors of the hypopharynx than in those with cancer of the oropharynx. Twelve (80%) of our patients demonstrated posterior pharyngeal segment dysfunction characterized by impaired pharyngeal constrictor motility. All 15 patients displayed pharyngeal stage abnormalities that limited bolus transport and clearance. CONCLUSIONS: Severe pharyngeal physiological abnormalities were present that led to impaired bolus transport and that were frequent and debilitating consequences of this organ-sparing protocol. Long-term follow-up of this group will be required to assess the permanence of the abnormalities.

Adult↗

Retinoic acid-induced thymic abnormalities in the mouse are associated with altered pharyngeal morphology, thymocyte maturation defects, and altered expression of Hoxa3 and Pax1.

Exogenous retinoic acid is teratogenic in animals and man, causing a spectrum of abnormalities termed retinoic acid embryopathy. Using a mouse model of retinoic acid embryopathy, our results show that exposure to all-trans retinoic acid (RA) on gestational day (gd) 9 results in thymic ectopia, hypoplasia, and thymocyte maturational defects. Immunohistochemical and flow cytometric analyses showed aberrant expression of stromal and thymocyte markers, and abnormalities in thymocyte development. RNA in situ hybridization for the transcription factors Hoxa3 and Pax1 was used to investigate the basis of this defect. Hoxa3 and Pax1 have been shown to be required for normal thymus development, and are normally expressed in the cells of the third pharyngeal pouch and third and fourth pharyngeal arches, involved in thymus organogenesis RA-exposed embryos showed an increased level of Hoxa3 expression in the neural tube and caudal pharyngeal arches as soon as 6 hr after exposure. The Pax1 expression pattern, in conjunction with analysis of the external pharyngeal morphology, showed that the development and structure of the third pharyngeal pouch and cleft were disrupted, resulting in a reduced third pharyngeal arch and/or fusion of the third and fourth arches. Changes in the expression of cellular retinoic acid binding protein (CRABP) and in the morphology of the cranial ganglia were consistent with altered neural crest cell migration from the caudal hindbrain after RA exposure. Together, our findings suggest that the teratogenic effects of RA on thymus development include changes in both the cranial neural crest and pharyngeal endoderm that contribute to thymus development. Further, the observed defects in thymus development may be mediated by RA-induced alterations in the expression of Hoxa3.

Animals↗