Decreased warfarin clearance associated with the CYP2C9 R150H (*8) polymorphism.

The cytochrome P450 (CYP) 2C9 R150H (*8) allele occurs commonly in African Americans and is associated with lower warfarin dose requirements. We conducted a pharmacokinetic study to examine whether the CYP2C9*8 allele impacts warfarin clearance in African-American patients. We also conducted an in vitro kinetic study of S-warfarin 7-hydroxylation using complementary DNA (cDNA)-expressed CYP2C9 enzymes. We observed a 30% reduction in the unbound oral clearance of S-warfarin and a 25% lower R- to S-warfarin plasma concentration ratio in patients with the CYP2C9*8 allele (n = 12) as compared to CYP2C9*1 homozygotes (n = 26). Consistent with these findings, the in vitro intrinsic clearance of S-warfarin was 30% lower with the cDNA-expressed R150H protein as compared to the wild-type protein. These data show that the R150H variant protein expressed by the CYP2C9*8 allele is associated with lower S-warfarin clearance. This finding provides clinical and experimental evidence to explain the lower warfarin dose requirements in patients with the CYP2C9*8 allele.

Genetic and clinical predictors of warfarin dose requirements in African Americans.

The objective of this study was to determine whether, in African-American patients, additional vitamin K oxidoreductase complex subunit 1 (VKORC1), cytochrome P450 2C9 (CYP2C9), CYP4F2, or apolipoprotein E (APOE) polymorphisms contribute to variability in the warfarin maintenance dose beyond what is attributable to the CYP2C9*2 and *3 alleles and the VKORC1 -1639G>A genotype. In a cohort of 226 African-American patients, weekly warfarin dose requirements were lower in those with the CYP2C9*8 allele (34 (30-47) mg; P = 0.023) and the CYP2C9 *2, *3, *5, *6, or *11 allele (33(28-40 mg); P < 0.001) as compared with those with the CYP2C9*1/*1 genotype (43 (35-56) mg). The combination of CYP2C9 alleles, VKORC1 -1639G>A genotype, and clinical variables explained 36% of the interpatient variability in warfarin dose requirements. By comparison, a model without the CYP2C9*5, *6, *8, and *11 alleles explained 30% of the variability in dose. No other VKORC1, CYP4F2, or APOE polymorphism contributed to the variance. The inclusion of additional CYP2C9 variants may improve the predictive ability of warfarin dosing algorithms for African Americans.

Low-molecular-weight heparin in pregnancy: peripartum bleeding complications.

OBJECTIVE: To compare bleeding complications in pregnant patients treated with low-molecular-weight heparin (LMWH) to untreated controls. STUDY DESIGN: A case-control study of patients from 2001 to 2005 who received prophylactic or therapeutic doses of LMWH during pregnancy was carried out. Indications for LMWH included current or prior thromboembolism, thrombophilia, or heart valve replacement. Controls were chosen in a 2:1 ratio to cases, matched for delivery route, and selected as the next two consecutive deliveries. The primary outcome was postpartum hemorrhage (PPH). Odds ratios (ORs) were calculated with 95% confidence intervals (CIs). RESULTS: Forty-nine women treated with LMWH delivered 55 infants. Current or prior thromboembolic disease was the anticoagulation indication in 15/55 (27.3%) and 26/55 (47%) of pregnancies, respectively. There were more obese gravidas (OR 3.91, CI 1.70 to 9.09) and labor induction was more common in the LMWH group, 25/55 (45%) vs 29/110 (26%), P=0.01. There was no difference in estimated blood loss (295.7+/-145.7 vs 308.6+/-111.9 cm(3), P=0.62 vaginal; 687.5+/-251.8 vs 765.0+/-313.2 cm(3), P=0.34 cesarean), PPH (6/55, 11% vs 9/110, 8.2% OR 1.37, CI 0.16 to 11.5) or transfusion (3/55, 5.4% vs 4/110, 3.6% OR 1.50, CI 0.3 to 7.48) between the cases and controls. There were two cases of postpartum pulmonary emboli, one with a maternal mortality. CONCLUSION: Bleeding complications, including PPH and transfusion, in patients treated with LMWH during pregnancy were not increased when compared to normal controls matched for delivery route.

Adenotonsillar histopathology after organ transplantation.

OBJECTIVES: The increasing number of surviving pediatric organ transplant recipients has resulted in a new clinical controversy surrounding the significance of adenotonsillar hypertrophy. The objective of this study is to evaluate adenotonsillar specimens, understand characteristic histopathology, and to examine the frequency and significance of this finding in this population. METHODS: Twenty-one cases of pediatric transplant recipients with adenoidal and/or tonsillar hypertrophy were reviewed retrospectively in a tertiary-care setting. Particular attention was given to the histopathology of their surgical specimens, including any evidence of posttransplantation lymphoproliferative disorders (PTLD). RESULTS: Using morphologic, immunohistochemical, and molecular genetic analyses, 15 (71%) of 21 patients were noted to have Epstein-Barr virus (EBV)-related lymphoid hyperplasia, including 1 case (4.7%) of PTLD. Six (29%) of 21 had evidence of reactive follicular hyperplasia not related to EBV. B-cell and T-cell markers were nearly uniformly positive when tested for, except in the single patient with PTLD, who exhibited polymorphic, polyclonal B-cell morphology. Kappa and lambda light-chain clonality markers were positive in 11 (92%) of 12 patients. CONCLUSIONS: EBV-related lymphoid hyperplasia is frequently associated with adenotonsillar hypertrophy in pediatric organ transplant patients (71% of our cases); 92% of those cases tested exhibit polyclonal B-cell populations. PTLD, an important cause of morbidity and mortality in this population, represented approximately 5% of our cases. The remainder of cases represent follicular hyperplasia unrelated to EBV or lymphoproliferative abnormalities. Characteristic histopathologic findings are presented.

Adenotonsillar hypertrophy and Epstein-Barr virus in pediatric organ transplant recipients.

OBJECTIVES/HYPOTHESIS: Epstein-Barr virus-related (EBV-related) lymphoid hyperplasia of the tonsils and adenoids is a precursor to post-transplantation lymphoproliferative disorder (PTLD). The incidence of post-transplantation adenotonsillar hypertrophy, a potential early sign of PTLD or EBV-related lymphoid hyperplasia, is not known. We sought to identify potential risk factors for adenotonsillar hypertrophy manifested as EBV-related hyperplasia and early PTLD in the pediatric solid organ transplant population. STUDY DESIGN: Cross-sectional analysis. METHODS: We developed a 65-point questionnaire concerning obstructive sleep disorder and upper respiratory tract infections and an 8-point focused physical examination, to identify prevalence of and risk factors for adenotonsillar hypertrophy in the pediatric transplant population. We evaluated 120 pediatric solid organ transplant recipients by parental questionnaire and focused adenotonsillar physical examination. RESULTS: Of the 120 patients, 62 had undergone liver transplantation and 58 had undergone kidney transplantation. Overall, the mean questionnaire score was 8.36 (range, 0-40) and the mean physical examination score was 3.86 (range, 1-8). Patients whose EBV serological test result was negative at the time of transplant had higher scores for both the questionnaire (mean score, 10.24) and the physical examination (mean score, 4.56) than those whose EBV serological test result was positive at the time of transplantation (scores of 7.38 and 3.30 for questionnaire and physical examination, respectively). The difference in examination scores was statistically significant (P <.003). CONCLUSIONS: Epstein-Barr virus seronegativity at the time of organ transplantation is a known risk factor for PTLD, with associated risk of developing EBV-related lymphoid hyperplasia. Our results indicate a higher incidence of symptoms and signs consistent with adenotonsillar hypertrophy in the EBV seronegative population. Adenotonsillar hypertrophy may be a precursor to EBV-related lymphoid hyperplasia and PTLD and must be identified in this patient population.

Academic otolaryngology in the new millennium: Are we falling behind?

OBJECTIVE: To determine if differences in publication rates have evolved over the past 3 decades for academic otolaryngologists. METHODS: Three random samples with 50 academic otolaryngologists each were studied. These otolaryngologists completed training in 1 of the 3 time periods (1970-74, 1980-84, 1990-94) studied. Articles published within the first 5 years after graduation were tabulated and statistically analyzed. RESULTS: Academic otolaryngologists graduating in the 1970s, 1980s, and 1990s averaged 8.7, 8.9, and 6.4 publications during their first 5 years of academic practice, respectively. The first 2 cohorts averaged 5.4 and 5.7 publications in the 4 major otolaryngology journals, versus 3.3 for 1990s graduates. Basic science publications increased for 1990s graduates over those of the 1970s and 1980s graduates. The percentage of first author articles remained stable. Despite these trends, only the drop in case reports was statistically significant (P = 0.023, ANOVA). CONCLUSION: Trends may be developing that predict decreasing publication rates for newly trained otolaryngologists entering academic practice.

Structural airway anomalies in patients with DiGeorge syndrome: a current review.

DiGeorge Syndrome is a genetic disorder characterized by either absence or hypoplasia of the thymus and the parathyroid glands. Patients with this syndrome also have a high incidence of cardiovascular malformations and facial dysmorphism. Structural airway anomalies have also been described, albeit infrequently. Tracheoesophageal fistula, short trachea with reduced numbers of tracheal rings, abnormal thyroid cartilage, laryngomalacia, tracheomalacia, and bronchomalacia have been recognized in these patients. We review all previously reported patients with DiGeorge syndrome and lower airway anomalies. In addition, we present 2 patients with DiGeorge syndrome who were each found to have an aberrant right tracheal bronchus. Structural airway anomalies can be a cause of morbidity and mortality in patients with DiGeorge syndrome. Prompt, thorough evaluation of the upper and lower airway in these patients is essential.

Tracheal stenosis and congenital heart disease in patients with Down syndrome: diagnostic approach and surgical options.

Upper airway obstruction is a prevalent feature in patients with Down syndrome. However, these patients may be completely asymptomatic in the early months of life. The recognition of a problem within the airway quite often occurs when these children present for cardiac surgery, diagnostic radiography with sedation, or during the induction and intubation for anesthesia. Tracheal stenosis is rare in the general population, but is seen somewhat more frequently in patients with Down syndrome. The incidence of tracheal stenosis in children with congenital heart disease, which is seen in 40% of patients with Down syndrome, has been reported to be 1.2%. Patients with Down syndrome also tend to have other upper airway obstructive pathology such as nasopharyngeal, oropharyngeal, and subglottic compromise. These entities, combined with the high incidence of cardiac disease, put these children at risk for acute and chronic cardiopulmonary compromise. We present two patients with Down syndrome and congenital heart disease who were found to have significant tracheal stenosis at the time of their cardiac surgery. The perioperative management of their airway defects including diagnostic evaluation and treatment modalities are discussed.

Third branchial cleft anomaly presenting as a retropharyngeal abscess.

Branchial cleft anomalies are congenital developmental defects that typically present as a soft fluctuant mass or fistulous tract along the anterior border of the sternocleidomastoid muscle. However, branchial anomalies can manifest atypically, presenting diagnostic and therapeutic challenges. Error or delay in diagnosis can lead to complications, recurrences, and even life-threatening emergencies. We describe a case of an infected branchial cleft cyst that progressed to a retropharyngeal abscess in a 5-week-old female patient. The clinical, radiographic, and histologic findings of this rare presentation of branchial cleft cyst are discussed.

Tracheobronchial foreign body management in an acutely ill neonate.

Pediatric foreign body management has become refined in recent years, both from a diagnostic and therapeutic standpoint. History, physical examination, and radiographic evaluation performed in a timely manner can lead to safe and successful foreign body retrieval. Advancement in videoendoscopic instrumentation and anesthetic techniques enable the airway surgeon to achieve simultaneous airway stabilization and foreign body removal. In the emergency setting, the surgeon may not have access to such instrumentation. We present a case of an acutely ill, extremely low birthweight infant who incurred foreign body aspiration. Basic tools of expediency and control of the airway remind us once again that technique must precede technology.

Increased female authorship in otolaryngology over the past three decades.

OBJECTIVE: To identify changing trends in female authorship and publication in the otolaryngology literature. METHODS: All articles published in the four major otolaryngology journals in each of the years 1978, 1988, and 1998 were reviewed. The authorship panel of each article was examined for number of authors, gender, educational degree category, and subspecialty area of publication. Data were analyzed for trends in female authorship and the association of gender with the other design variables. RESULTS: A total of 2,463 articles were analyzed. The average percentage of female authorship increased from 4.1% in 1978 to 8.7% in 1988 and 12.4% in 1998, and the percentage of articles with a female "first author" increased from 3.2% to 7.4% and 11.4% for the same years, respectively. Each of these increases was statistically significant (P < .001). The weighted rank of female authorship also increased from 0.063 to 0.164 and 0.243 for the same years, respectively (P < .001). With respect to subspecialty publication, women were first authors of 14.7% of articles concerning pediatric otolaryngology but accounted for 9.9% or less of the first authors in the other subspecialty areas (P < .001). Female authors were also much more likely to be nonphysicians (P < .001) than men. CONCLUSIONS: There has been a significant trend toward increased female authorship in the otolaryngology literature. A significant portion of this is accounted for by nonphysician female authors, and female authorship tends to be concentrated in pediatric otolaryngology.

Adenotonsillar enlargement in pediatric patients following solid organ transplantation.

OBJECTIVE: To evaluate the management of adenotonsillar hypertrophy in pediatric patients after transplantation. DESIGN: A retrospective medical record review after transplantation of all pediatric patients undergoing adenotonsillectomy at the University of California, Los Angeles, Medical Center during a 14-month period. SETTING: A tertiary care center. PATIENTS: There were 16 patients in our review, 11 boys and 5 girls. Nine patients had undergone liver transplantation, and 7 had undergone kidney transplantation. INTERVENTION: Fourteen patients underwent adenotonsillectomy, and 2 underwent adenoidectomy alone. Indications for surgical intervention included progressive symptoms of upper airway obstruction, recurrent tonsillitis, and/or evidence of notable adenotonsillar enlargement on physical examination. RESULTS: The mean +/- SD age at the time of transplantation was 3 years 1 month +/- 3 years 5 months. The mean +/- SD duration from allograft transplantation to adenotonsillectomy was 5 years 1 month +/- 2 years 4 months. Histopathologic examination revealed that 1 kidney transplant recipient had posttransplantation lymphoproliferative disorder. Eleven patients were found to have Epstein-Barr virus-related lymphoid hyperplasia. All patients experienced clinical resolution of their symptoms after surgery. CONCLUSIONS: Posttransplantation lymphoproliferative disorder is a condition associated with the Epstein-Barr virus infection in the setting of immunosuppression. Early presentation of posttransplantation lymphoproliferative disorder in children may be manifested by adenotonsillar enlargement. In addition to the role in relieving upper airway obstruction and decreasing upper respiratory tract infection, adenotonsillectomy may be critical in the prompt evaluation and treatment of posttransplantation lymphoproliferative disorder.

Documentation of the prevalence of penicillin-resistant Streptococcus pneumoniae isolated from the middle ear and sinus fluid of children undergoing tympanocentesis or sinus lavage.

With increasing pneumococcal resistance to penicillin and other antibiotics, use of antibiotic therapy for children with upper respiratory tract infections such as otitis media and sinusitis has become difficult. Selecting an appropriate treatment regimen has become more challenging due to frequent concomitant microbial resistance to multiple antibiotics. In a prospective, nonrandomized study, we obtained middle ear and sinus aspirate specimens from all children undergoing outpatient tympanocentesis or sinus lavage for any indication at our institution over two 4-week periods. One hundred fifty-four specimens were obtained. Of these, 12 grew Streptococcus pneumoniae, 7 of which were resistant to penicillin. A 6-month retrospective review of these patients' medical histories evaluated their antibiotic use prior to surgical intervention. An association between penicillin resistance and recent use of 2 or more antibiotics in children with positive S pneumoniae cultures was confirmed, as has been documented in prior reports. Those with penicillin-resistant S pneumoniae also demonstrated a higher incidence of multidrug-resistant organisms.

Giant juvenile xanthogranuloma of the tongue.

Juvenile xanthogranulomas (JXGs) are rare, benign, fibrohistiocytic lesions. They usually appear as one or more cutaneous papules on the head, neck, or trunk in infants. Twelve cases of oral JXGs have been reported, four of which involved the tongue. We present a 6-year-old girl with a large tongue mass diagnosed as JXG after an excisional biopsy. Histological and immunohistochemical staining results are presented. This is the first reported case of a giant oral JXG. A review of the literature on these unusual lesions is presented, along with discussion of their differential diagnosis and key aspects of the patient's evaluation, management, and pathological diagnosis.

Rigid tracheobronchoscopy-induced bacteremia in the pediatric population.

OBJECTIVE: To assess the incidence of bacteremia following rigid tracheobronchoscopy in children to determine whether use of prophylactic antibiotics is warranted in pediatric patients at risk for perioperative endocarditis. DESIGN: Prospective nonrandomized clinical study. SETTING: Specialty care referral center. PATIENTS: Patients younger than 18 years undergoing diagnostic rigid tracheobronchoscopy for airway assessment. Twenty-five patients (14 boys and 11 girls) were enrolled. The mean age was 5.2 years (range, 10 months to 13 years). INTERVENTIONS: Blood samples for culture were obtained intraoperatively at 2 time intervals. The first culture was obtained after the induction of mask anesthesia prior to airway instrumentation; the second, within 5 minutes following the completion of tracheobronchoscopy. Blood cultures were performed under sterile technique and were placed into 20 mL of brain heart infusion broth. All cultures were incubated at 35 degrees C and observed for growth over a 14-day period. RESULTS: There were no documented cases of bacterial growth in blood cultures. All blood cultures, obtained before and after tracheobronchoscopy, were negative for bacterial growth after incubation for 14 days. Two culture bottles yielded contaminant organisms. CONCLUSIONS: Rigid tracheobronchoscopy in the pediatric population is a low-risk procedure for the development of bacteremia. This may bear on present guidelines regarding perioperative antibiotic prophylaxis for endocarditis in the high-risk population.

Evaluation and management of benign, non-congenital tongue masses in children.

Lingual tumors are rare, primarily benign, lesions in the pediatric population. Congenital lesions, such as hemangiomas, lymphatic malformations, dermoids, hamartomas and thyroglossal ducts cysts, are seen more commonly. Primary, non-congenital lingual neoplasms are less common in children. We present three patients with benign lingual neoplasms. Evaluation, management, pathology and follow-up are discussed.

Adenotonsillectomy in the very young patient: cost analysis of two methods of postoperative care.

Postoperative management of the patient younger than 36 months undergoing adenotonsillectomy has been the subject of many debates. Concerns for early postoperative complications such as airway obstruction, emesis, dehydration, and hemorrhage have led many physicians to consider overnight hospitalization following adenotonsillectomy in very young children. Trends in health care management have had increasing focus on cost effective means of treating patients to limit unnecessary expenditure on the part of the patient, physician, and hospital facility. The purpose of this retrospective review was to analyze two methods of early postoperative management in children less than 36 months old undergoing adenotonsillectomy at the Children's Hospital, San Diego from 1992 to 1997. Three hundred and seven cases were reviewed. Same-day discharge was compared with overnight inpatient observation based on the cost analysis of these two methods of postoperative care. Postoperative care was based on length of stay in the recovery room and as an inpatient. Expense of postoperative care was based on cost calculation for the recovery room and overnight hospitalization. Of the 307 patients, 194 went home the day of surgery and 113 were observed overnight in the hospital. Average hospital cost was higher in the outpatient group than in the inpatient group (P < 0.001). This difference reflects longer recovery room stay (350 min) in the outpatient group compared to the inpatient group (108 min) (P < 0.001). Outpatient adenotonsillectomy in the patient under 36 months may be safe; however, prolonged recovery room stays may actually make outpatient surgery less cost-effective than overnight admission. Recovery room costs are significantly higher per unit time than costs of inpatient hospitalization. Further investigation of cost-effective outpatient observation units may improve cost containment in the outpatient surgical setting.