Comparative meta-analysis of host transcriptional response during Streptococcus pneumoniae carriage or infection.

Infection with Streptococcus pneumoniae causes over 150,000 cases of pneumonia annually in the United States alone. We performed a meta-analysis of publicly available RNA-sequencing data to compare the host-specific intracellular transcriptional responses that differ between infection and carriage with S. pneumoniae in humans and mice. We applied an automated preprocessing workflow to collections of publicly available fastq files that were categorized as either of two phenotypes-infection or carriage in humans and mice. We identified the differentially expressed genes and intracellular signaling pathways that changed in host cells during infection or carriage and whether these human phenotypes could be appropriately modeled at the molecular level in mice. Although we observed multiple differentially expressed genes shared among multiple comparisons, we found no overlapping significant signaling pathways between the mouse and human studies in either phenotype. Based on the samples included in this secondary analysis, we identified a minimal number of generalized transcriptional relationships between host infection and carriage phenotypes of S. pneumoniae that were consistently shared between the mouse and human hosts. Our findings suggest that additional controlled datasets in mouse and human carriage or infection models are needed to better understand the underlying mechanism(s) of invasion and pathogenesis. This knowledge could then contribute to the development of improved prophylactics and/or therapeutics against this pathogen.

Nasal and sinus symptoms and chronic rhinosinusitis in a population-based sample.

BACKGROUND: The objective of this study was to describe the first US-based study to use the European Position Paper on Rhinosinusitis (EPOS) criteria to study the prevalence of chronic rhinosinusitis (CRS) in a general-population sample. METHODS: A CRS symptom questionnaire was mailed to 23 700 primary care patients from Geisinger Clinic, a health system serving 45 counties in Pennsylvania. CRS cases were categorized into four unique subgroups based on EPOS symptoms: obstruction and discharge with no smell loss or pain/pressure; smell loss without pain/pressure; facial pain and/or pressure without smell loss; and both smell loss and pain/pressure. All cases were required to have nasal obstruction or discharge. Logistic regression was used to evaluate potential factors associated with CRS subgroups. RESULTS: We found that 11.9% of patients met criteria for CRS. Prevalence peaked at 15.9% between ages 50 and 59 years and then dropped to 6.8% after age 69. The odds of CRS was higher among patients who were white, younger, smokers, had a history of Medical Assistance, and had other diseases. When CRS subgroups were modeled separately, these associations were no longer significant for some CRS subgroups. Comorbid diseases were most strongly associated with CRS cases who reported smell loss and facial pain and/or pressure and had the weakest associations with CRS cases who did not report these symptoms. CONCLUSIONS: CRS is a highly prevalent and heterogeneous condition. Differences in risk factors and health outcomes across symptom subgroups may be indicative of differences in etiology that have implications for disease management.

Five-year risk of incident disease following a diagnosis of chronic rhinosinusitis.

BACKGROUND: Chronic rhinosinusitis (CRS) has a broad range of comorbidities. Due to a lack of longitudinal studies, it is not known whether these comorbidities cause CRS, are promoted by CRS, or share a systemic disease process with CRS. OBJECTIVE: The objective of this study was to determine the risk of incident disease within 5 years after a new diagnosis of CRS with nasal polyps (CRSwNP) and without nasal polyps (CRSsNP). METHODS: We conducted a case-control study nested within the longitudinal cohort of primary care patients in the Geisinger Clinic using electronic health record data. We evaluated incident disease over 5 years in newly diagnosed CRSwNP and CRSsNP cases compared to controls using multivariable Cox regression models. RESULTS: CRSsNP (n = 3612) cases were at greater risk (HR, 95% confidence interval) than controls for incidence of: upper airway diseases, including adenotonsillitis (3.29, 2.41-4.50); lower aerodigestive tract diseases, including asthma (2.69, 2.14-3.38); epithelial conditions, including atopic dermatitis (2.75, 1.23-6.16); and hypertension (1.38, 1.19-1.61). CRSwNP (n = 241) cases were at greater risk for obesity than controls (1.74, 1.08-2.80), but CRSwNP was not associated with other diseases. CONCLUSION: The risk of other diseases associated with CRS adds to the burden of an already highly burdensome condition, and suggests either that CRS promotes onset of other diseases or is an indicator of systemic disease processes. Different patterns of association with diseases by CRS phenotype may be due to CRSwNP sample size limitations or reflect a different pattern of disease onset by phenotype. These findings have implications for screening guidelines and care of CRS patients.

Pediatric cardiology in the 1990s.

OBJECTIVES: In 1991, all active board-certified pediatric cardiologists were polled by questionnaire to examine the relation of subspecialty training and motivational and satisfaction issues to practice characteristics. BACKGROUND: Previous questionnaires with regard to manpower status and practice characteristics were published in 1967 and 1980. These indicated a field predominantly centered in academic medicine with growth in manpower close to predicted need. METHODS: The questionnaire was mailed to 844 of 884 active board-certified pediatric cardiologists and was returned anonymously by 570, a 68% response rate. RESULTS: Among respondents, the mean year in which fellowship training was completed was 1974. The average length of subspecialty training was 31 months for all respondents and 34 months among those completing training since 1981. Seventy-seven percent of subspecialty training centered on clinical training. Although there has been a slight increase in research training in recent years, only 18 respondents completed > or = 22 months of research training. Respondents devote a mean of 89% of professional hours to subspecialty activities and spend 63% of total hours in clinical care. Total hours, income and procedures were related to site of professional activity. Professional satisfaction was high in the factors considered more important: professional challenge and interaction, clinical resources, career security and clinical autonomy. CONCLUSIONS: The field of pediatric cardiology is a subspecialty centered on patient care and performance of diagnostic and interventional techniques. Professional activities varied according to practice site. Pediatric cardiologists with basic research training and professional activity remain a minority. Satisfaction is high, with greatest satisfaction in professional interactions and least satisfaction with income and free time.

Neuroendocrine tumors. A European view.

A center in Belfast, Northern Ireland, has established a register for tumors of the gastroenteropancreatic endocrine system. Carcinoid tumors occur most frequently. Of the non-carcinoid tumors, insulinomas, gastrinomas, and unknown types have the highest incidence, with other types being extremely rare. The potentially remediable nature of the tumors is stressed, and frequently a good quality of life can be experienced even in the presence of metastatic disease. The syndromes are probably underdiagnosed as they present with clinical features for which there are more common explanations, and appropriate diagnostic methods are therefore not used. The management of the syndromes is reviewed with particular emphasis on the treatment of patients with inoperable disease. Histamine (H2)-receptor antagonist therapy has made an impact in Zollinger-Ellison syndrome, and streptozotocin and somatostatin analogues can control tumor growth and endocrine syndromes, respectively.

Indium-111 autologous leukocyte imaging in pancreatitis.

Thirty-nine patients with acute pancreatitis have been assessed using a prognostic factor grading system, abdominal ultrasound, and autologous leukocyte imaging. Both prognostic factor grading and leukocyte imaging can accurately assess the severity of the disease early in its course. All patients with a negative indium-labeled leukocyte image recovered without sequelae, whereas five of the 12 patients with a positive image developed complications, including two deaths. Abdominal ultrasound is of no value in assessing severity, but is a useful method of detecting those patients with gallstone-associated disease. In patients with suspected abscess formation following acute pancreatitis, indium leukocyte imaging does not differentiate between fat necrosis and abscess formation. In this situation, computerized tomography should be carried out before laparotomy is undertaken.

Relation between intragastric bile acid concentration and mucosal abnormality in the stomach after vagotomy and gastroenterostomy for duodenal ulcer.

A high incidence of possible premalignant conditions of the gastric mucosa has been reported in the postoperative stomach and it has been suggested that bile plays a role in their pathogenesis. Fifty eight patients who had had a vagotomy and gastrojejunostomy between 1957 and 1967 underwent endoscopy and biopsy. Subsequently, samples of fasting and postprandial gastric juice were taken from all patients for analysis of total bile acid. The patients were divided into three histological groups: group 1 (24 patients) had gastritis or mucosal atrophy but no more than mild dysplasia; group 2 (23 patients) had intestinal metaplasia in one or more biopsies; group 3 (11 patients) had moderate or severe dysplasia in one or more biopsies. Group 2 and group 3 patients had higher fasting intragastric bile acid concentrations than group 1 (p less than 0.01 in both cases). There was no difference between fasting bile acid concentrations in groups 2 and 3. In the postprandial phase groups 2 and 3 also had higher peak intragastric concentrations than group 1 (p less than 0.01 in both cases). Again, there was no significant difference between groups 2 and 3. It is concluded that there is a relation between mucosal abnormality in the postoperative stomach and intragastric bile acid concentration. The possible aetiological link between bile acid and these mucosal abnormalities is discussed.

Relation between gastric histology and gastric juice pH and nitrite and N-nitroso compound concentrations in the stomach after surgery for duodenal ulcer.

Formation of N-nitroso compounds in gastric juice has been implicated in the pathogenesis of cancer in the stomach after operation. Gastric juice was aspirated from 85 subjects: 23 were controls, 51 had previously undergone vagotomy and gastrojejunostomy, and 11 had previously undergone vagotomy and pyloroplasty. The gastric juice samples were analysed for pH, nitrite, and total N-nitroso compounds. A significant correlation was found between pH and nitrite concentration (p less than 0.01). No significant correlation was found between pH and total N-nitroso compound concentration or between nitrite and N-nitroso compound concentration. The vagotomy and gastrojejunostomy patients had higher pH values and higher concentrations of nitrites and N-nitroso compounds than controls (p = 0.01 in all cases). The 51 vagotomy and gastrojejunostomy patients also underwent endoscopy and biopsy. They were divided into three groups: group 1 (21 patients) had no intestinal metaplasia and no more than mild dysplasia; group 2 (20 patients) had intestinal metaplasia; and group 3 (10 patients) had moderate or severe dysplasia. Groups 2 and 3 both had higher pH values and higher nitrite concentrations than group 1 (p = 0.01 in all cases). There was no significant difference, however, between either group 2 or 3 and group 1 for total N-nitroso compound concentration. Since there was no simple linear relation between pH and N-nitroso compound concentration, it was concluded that formation of N-nitroso compounds at high pH was unlikely to be involved in the pathogenesis of gastric cancer in the hypochlorhydric stomach after operation. The relation between nitrite and histological abnormality was not associated with a similar relation between N-nitroso compounds and histological abnormality. It therefore appears that there is no simple relation between N-nitroso compounds and the pathogenesis of premalignant gastric mucosal changes.

The CT appearance of thyroglossal duct carcinoma.

BACKGROUND AND PURPOSE: Thyroid carcinoma arising in a thyroglossal duct cyst may be clinically indistinguishable from a benign thyroglossal duct cyst. The preoperative diagnosis of carcinoma, however, can have important implications for surgical planning and postoperative treatment. Our purpose was to describe the CT appearance of thyroglossal duct carcinoma and identify the features that distinguish thyroglossal duct carcinoma from benign thyroglossal duct cysts. METHODS: Retrospective review of the medical records from the University of Pittsburgh Medical Center and Geisinger Medical Center (Danville, Pennsylvania) identified six patients with papillary thyroid carcinoma within the thyroglossal duct who had undergone preoperative CT examinations of the neck. There were two women and four men. Their ages ranged from 14 to 59 years. Three patients underwent contrast-enhanced CT of the neck, and three underwent unenhanced CT. All CT examinations consisted of 3- to 5-mm-thick contiguous axial sections. RESULTS: Each patient had an anterior neck mass with a cystic component. Two of the masses had dense or enhancing mural nodules, two had irregular calcification throughout the mass, and two had dense or enhancing mural nodules with additional foci of calcification. One patient had cervical lymphadenopathy. CONCLUSION: Carcinoma should be considered in thyroglossal duct cysts that have a mural nodule or calcification or both.

Epiglottic reconstruction of laryngeal stenosis secondary to cricothyroidostomy.

Two cases of laryngeal stenosis secondary to cricothyroidostomy are presented with their management. Both laryngeal injuries involved the glottis and subglottis regions with the second case sustaining total closure of the larynx by scar tissue. Although different surgical procedures were employed, management was successful in each case with one surgical attempt. Total glottic and subglottic reconstruction was necessary in the second case and was successfully handled with a modification of the epiglottic laryngoplasty. The surgical technique is described in detail. Caution is raised concerning the routine use of cricothyroidostomy. Epiglottic laryngoplasty is presented as a simple and encouraging procedure for laryngeal reconstruction of laryngeal stenosis.

Warthin's tumor: a review indicating no male predominance.

There is probably no other head and neck group of tumors as those found in the parotid gland that constitute such a diversity of growths, both benign and malignant. Warthin's or papillary cystadenoma lymphomatosum is the second most common benign tumor of the parotid gland. One universally held clinical characteristic of this tumor is its high male ratio. Because of a high frequency of female Warthin's tumor seen at Geisinger Medical Center, a review of all primary parotid gland tumors from 1971 to 1981 was carried out. Sixty-two cases out of 204 primary neoplasms were classified as Warthin's. There was no significant difference in the number of male and female cases with 32 males and 30 females. The clinical characteristics of Warthin's tumor and this unusually high female occurrence are discussed.

Cystic hygroma-lymphangioma: a rare and still unclear entity.

Hygroma cysticum coli or cystic hygroma remains a complex entity in terms of its development and management. Most recently, cystic hygroma has been categorized as part of a larger spectrum that includes lymphangiomas. The majority of lymphangiomas occur in the head and neck as cystic hygromas with the posterior cervical region as the most common site. Since its original description, there have been many attempts at treatment modalities: surgical excision remains the treatment of choice. The literature is reviewed and 40 cases from the author's institution are presented. The purposes of this review are, first, to bring some order to the theories and development of this lesion and its various pathological presentations. Second, to approach the treatment of these difficult lesions in an objective manner and to set up guidelines for management.

Middle ear effusions and the nitrous oxide myth.

Myringotomies were performed on 75 ears suspected of having chronic or recurrent otitis media with effusion. Preanesthesia and intraoperative tympanograms with halothane, nitrous oxide, and oxygen anesthesia were compared for possible changes in middle ear pressure due to anesthesia. In addition, preanesthesia tympanograms were compared with tympanograms taken 2 weeks before hospital outpatient surgery. Tympanograms of 11 ears were found to shift from a flat type recorded at the office visit to normal range at pre and postinduction anesthesia. Middle ear fluid was not present in any of these 11 ears. The remaining 64 ears were broken down into three abnormal tympanogram configurations; flat, roll-over, and peaked negative pressure types. Comparing the tympanograms done in the office, preanesthesia and intraoperatively, only one of the 64 ears showed a change after induction of anesthesia. Three of the 64 ears revealed an unpredictable result with negative myringotomies. These results tend to support tympanometry as a means in predicting myringotomy findings, and also refute the contention that short-term nitrous oxide anesthesia changes the middle ear effusion during myringotomy.

Carotid rupture and tissue coverage.

Carotid rupture following the treatment of head and neck malignancy is the most dreaded complication faced by the head and neck surgeon. Tissue coverage of the carotid artery has been advocated as the method of protection likely to prevent carotid rupture. A retrospective study was carried out to assess the benefit of carotid coverage and whether such protection plays a role in decreasing mortality and morbidity. A brief history of carotid protection is presented. A series of 194 head and neck cancer patients who underwent resection of their mucosal primary in continuity with radical neck dissection over a ten-year period was reviewed. No coverage was used in 120 cases, while 72 cases received carotid coverage. There was a 13% fistula rate and a 15% rate of wound complication without fistula. Six patients without recurrence who had carotid rupture or ligation for imminent rupture were identified. This group was scrutinized with regard to several parameters. Three received tissue coverage of the carotid system, while the other three were left unprotected. There was 50% mortality rate and 25% rate of neurologic sequelae amongst the survivors. This review tends not to support the premise that tissue coverage is a major factor in the prevention of carotid rupture.

Surgical management of localized amyloidosis.

OBJECTIVE: To demonstrate the role of two-dimensional reconstruction images on computed tomography (CT) in the treatment planning for laryngeal amyloidosis. To discuss the treatment for isolated laryngeal amyloidosis and compare the role of endoscopic versus an open surgical approach to management. STUDY DESIGN: Retrospective review. METHODS: The medical records from 1984 to the present with the diagnosis of localized respiratory tract amyloidosis at Geisinger Medical Center were reviewed. RESULTS: Five previously unpublished cases of localized laryngeal amyloidosis were identified with the supraglottic region the major site of involvement. Hoarseness and airway compromise were the presenting symptoms. CT two-dimensional reconstruction imaging was used to evaluate two cases with extensive laryngeal involvement that required an external surgical approach to relieve symptoms. CONCLUSIONS: Localized laryngeal amyloidosis is a rare disease that requires surgical management when symptomatic. CT two-dimensional reconstruction can be helpful in detailing the extent of disease and planning surgery. A lateral external supraglottic approach has been found to be successful in treating patients with large supraglottic masses.

Laryngospasm induced pulmonary edema.

Two case reports of laryngospasm-induced pulmonary edema following general anesthesia are presented. Therapy consisted of immediate reintubation, application of positive pressure ventilation, and diuresis. This phenomenon should be recognized rapidly with appropriate therapy instituted immediately to avoid other complications. Preventive measures are discussed and a modified protocol of the management is outlined.

Thyroglossal duct carcinoma: a rational approach to management.

OBJECTIVE: To discuss the authors' experience with thyroglossal duct carcinoma and present a rational approach to the management of this entity. STUDY DESIGN AND METHODS: A retrospective review of the cytopathology and pathology records of all patients with the diagnosis of a thyroglossal duct remnant from 1965 to 1997 was performed. RESULTS: Three cases of papillary thyroglossal duct carcinoma were identified, with one suspected squamous cell carcinoma by needle aspiration. The papillary carcinomas are discussed in detail to illustrate the difficulty encountered in managing the thyroid gland in the setting of a thyroglossal duct carcinoma. Fine-needle aspiration proved effective in making the diagnosis preoperatively. CONCLUSIONS: The authors recommend that a thyroglossal duct cyst with a microscopic focus of papillary carcinoma, without cyst wall invasion, be managed with a Sistrunk procedure. Treatment of all other thyroglossal duct papillary carcinomas should include removal of all thyroid tissue followed by radioactive iodine treatment.

Cystic hygroma/lymphangioma: a rational approach to management.

OBJECTIVE: To outline a rational approach to the management of cystic hygroma based on the authors' experience, the natural history of the disease, and the results of surgical treatment. STUDY DESIGN AND METHODS: A retrospective review of all patients with the diagnosis of lymphangioma or cystic hygroma from 1958 to 2000 was performed. RESULTS: Seventy-four patients were identified with 46 cases confined to the cervicofacial region. Surgical excision was performed on 60 of the 74 cases involving all regions of the body and 34 of the 46 patients with head and neck lesions. The location of the malformation is the most important determinate for surgical success. While surgical excision was the main treatment modality, 11 of 12 untreated patients were noted to improve, with 8 patients showing complete resolution. CONCLUSIONS: In the treatment of lymphangiomas, the physician should be experienced in the management of such lesions, be aware of spontaneous resolution, and recognize the limitations and potential harm of surgery in certain instances.

Curettage of nontuberculous mycobacterial cervical lymphadenitis.

Cervicofacial nontuberculous mycobacterial infections of the head and neck are difficult to treat surgically because of their common location near the branches of the facial nerve. Curettage of these lesions through a small skin incision makes treatment simple without injury to the facial nerve fibers and leaves the patient with an excellent cosmetic result. Most discussions on the topic, however, favor complete surgical excision even though curettage has been reported as a safe and excellent means of treatment. For the past 2 years, the department of otolaryngology-head and neck surgery at the Geisinger Medical Center, Danville, Pa, has used curettage in seven patients as the primary treatment modality for these facial and cervical infections. A review of these cases is presented.