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Biomedical subjects

K D Olsen

Publications and source records attributed to K D Olsen.

At least 73 records · Page 4Linked to original sources

Induction of suppurative arthritis in rabbits by Haemophilus endotoxin, tumor necrosis factor-alpha, and interleukin-1 beta.

Because Haemophilus influenzae type b (Hib) is the principal cause of suppurative arthritis in young children and its lipooligosaccharide (LOS) is thought to be the main virulence factor, Hib endotoxin was evaluated for its ability to induce synovial inflammation in rabbits. Also, the role of the cytokines tumor necrosis factor-alpha (TNF alpha) and interleukin-1 beta (IL-1 beta) in mediating the synovial inflammatory process was studied. Intraarticular inoculation of 2 pg to 20 ng of Hib LOS produced a dose-dependent increase in concentrations of leukocytes and protein in synovial lavage fluid that was significantly modulated by concomitant administration of rabbit TNF alpha- and rabbit IL-1 beta-specific antibodies. Inoculation of joints with either 10(4) IU of rabbit TNF alpha or 10 ng recombinant rabbit IL-beta induced synovial inflammatory changes similar to those observed after LOS intraarticular challenge. These data provide evidence for the role of Hib LOS in inducing suppurative arthritis and for the critical participation of TNF alpha and IL-1 beta in the initial events of the synovial inflammatory response.

Animals↗

Characteristics of experimental Candida albicans infection of the central nervous system in rabbits.

Different concentrations (10(7), 10(5), 10(3) cfu/ml) of Candida albicans were injected intracisternally in rabbits. The highest inoculum was fatal within 14 h in all animals. In recipients of 10(5) and 10(3) cfu/ml inocula, the mean +/- SD peak cerebrospinal fluid (CSF) tumor necrosis factor-alpha (TNF alpha) concentrations were 1.6 +/- 2.42 and 0.3 +/- 0.59 ng/ml, respectively, at 6 h; the mean +/- SD CSF leukocyte and protein concentrations were 6291 +/- 6515 and 453 +/- 674 cells/mm3 (at 24 h) and 118 +/- 90 and 109 +/- 122 mg/dl (at 12 and 24 h), respectively. At 6-10 days after inoculation, a second peak of TNF alpha activity was accompanied by increased CSF inflammation. Mortality in the 10(5) and 10(3) cfu/ml inoculum groups was 56% and 22%, respectively. Fatal infection was associated with higher second CSF peak TNF alpha and leukocyte concentrations and a larger proportion of culture-positive CSF samples. Histopathology revealed hyphal invasion, vasculitis, abscesses, and acute and chronic inflammatory infiltration of meninges and brain parenchyma. This model can be useful for evaluation of the pathogenesis and therapy of central nervous system fungal infections.

Animals↗

Enhanced attenuation of meningeal inflammation and brain edema by concomitant administration of anti-CD18 monoclonal antibodies and dexamethasone in experimental Haemophilus meningitis.

Antiinflammatory therapy has been shown to reduce the adverse pathophysiological consequences that occur in bacterial meningitis and to improve outcome from disease. In the present study, modulation of two principal steps of the meningeal inflammatory cascade was accomplished by concomitant administration of dexamethasone to diminish overproduction of cytokines in response to a bacterial stimulus and of a monoclonal antibody directed against adhesion-promoting receptors on leukocytes to inhibit recruitment of white blood cells into the subarachnoid space. Dexamethasone and antibody therapy produced a marked attenuation of all indices of meningeal inflammation and reduction of brain water accumulation after H. influenzae-induced meningitis in rabbits compared with results of each agent given alone and of untreated animals. In addition, the enhanced host's meningeal inflammatory reaction that follows antibiotic-induced bacterial lysis was profoundly ameliorated when dual therapy was administered without affecting clearance rates of bacteria from cerebrospinal fluid and vascular compartments. The combination of both therapeutic approaches may offer a promising mode of treatment to improve further the outcome from bacterial meningitis.

Animals↗

Tumor necrosis factor alpha/cachectin and interleukin 1 beta initiate meningeal inflammation.

Although previous studies using human cytokines in rabbits and rats have provided evidence of the participation of tumor necrosis factor alpha (TNF-alpha) and interleukin 1 beta (IL-1 beta) in the meningeal inflammatory cascade, the results obtained by several groups of investigators have been discordant or, at times, contradictory. In the present study, homologous cytokines were applied to the rabbit meningitis model. Intracisternal administration of 10(2)-10(5) IU of purified rabbit TNF-alpha (RaTNF-alpha) produced significant cerebrospinal fluid (CSF) inflammation. A similar response was observed after intracisternal inoculation of 5-200 ng of rabbit recombinant IL-1 beta (rrIL-1 beta). Preincubation of these two mediators with their specific antibodies resulted in an almost complete suppression of the CSF inflammatory response. In animals with Haemophilus influenzae type b lipooligosaccharide-induced meningitis, intracisternal administration of anti-rrIL-1 beta, anti-RaTNF-alpha, or both resulted in a significant modulation of meningeal inflammation. Simultaneous administration of 10(3) IU of RaTNF-alpha and 5 ng of rrIL-1 beta resulted in a synergistic inflammatory response manifested by a more rapid and significantly increased influx of white blood cells into the CSF compared with results after each cytokine given alone. These data provide evidence for a seminal role of TNF-alpha and IL-1 beta in the initial events of meningeal inflammation.

Animals↗

Detection of interleukin 1 beta but not tumor necrosis factor-alpha in cerebrospinal fluid of children with aseptic meningitis.

Tumor necrosis factor-alpha and interleukin 1 beta have been shown to be mediators of meningeal inflammation in animal models of bacterial meningitis. The presence of both cytokines in cerebrospinal fluid (CSF) of patients with bacterial meningitis has been documented recently. In this study, we measured concentrations of interleukin 1 beta and tumor necrosis factor-alpha in CSF samples from 36 patients with nonbacterial (aseptic) meningitis, 13 of whom had culture-proved enteroviral meningitis, and from 14 control patients. None of the samples from patients with aseptic meningitis and from the controls had detectable tumor necrosis factor activity in CSF. Thirty-two (89%) of 36 patients with aseptic meningitis had detectable interleukin 1 beta in CSF (mean +/- SEM, 48 +/- 11 pg/mL). These concentrations were significantly smaller than those previously reported in patients with bacterial meningitis (944 +/- 128 pg/mL). Only 2 of the 14 control patients had detectable CSF interleukin 1 beta concentrations of 21 and 42 pg/mL. A significant correlation was evident between interleukin-1 beta concentrations and white blood cell counts in the CSF of patients with aseptic meningitis. Our data suggest that the initial events of CSF inflammation in children with aseptic meningitis are different than those in patients with bacterial meningitis, and the participation of these two cytokines, especially tumor necrosis factor-alpha, is less critical to the process.

Adolescent↗

Cerebrospinal fluid prostaglandins, interleukin 1 beta, and tumor necrosis factor in bacterial meningitis. Clinical and laboratory correlations in placebo-treated and dexamethasone-treated patients.

Prostaglandins (PGs), interleukin 1 beta (IL-1 beta), and tumor necrosis factor alpha (TNF alpha) are likely mediators of local inflammatory reactions. We measured PGE2, PGI2, IL-1 beta, and TNF concentrations in paired cerebrospinal fluid (CSF) samples (on admission, CSF1, and 18 to 30 hours later, CSF2) from 80 infants and children with bacterial meningitis. Forty patients received dexamethasone sodium (0.6 mg/kg per day in four intravenous doses) and 40 received an intravenous saline placebo. In CSF1, PGE2, PGI2, IL-1 beta, and TNF were detected in 90%, 56%, 98%, and 71% of specimens with mean (+/- SEM) concentrations of 462 +/- 65, 377 +/- 62, 1266 +/- 242, and 799 +/- 227 pg/mL, respectively. Concentrations of PGE2 correlated significantly with PGI2, IL-1 beta, TNF, and lactate and inversely correlated with glucose concentrations in the first CSF specimens. The PGE2, PGI2, IL-1 beta, and TNF were still detected in 40%, 18%, 97%, and 60%, respectively, of second CSF specimens obtained from placebo-treated patients. Compared with patients who had detectable PGI2 or TNF alpha concentrations in CSF2 specimens, those placebo-treated patients with no detectable PGI2 or TNF alpha activity in CSF2 had a lower incidence of neurological sequelae. Dexamethasone-treated patients had significantly lower PGE2, IL-1 beta, and lactate concentrations and higher glucose concentrations in CSF 18 to 30 hours later, shorter duration of fever, and a lower incidence of neurological sequelae than did placebo-treated patients.

Bacterial Infections↗

Nasal influences on snoring and obstructive sleep apnea.

Although the relationship between nasal obstruction and sleep disturbance is variable, either partial or total obstruction of the nasal passages can cause snoring, obstructive sleep apnea, and the sequelae of alveolar hypoventilation. In addition, nasal obstruction can cause sleep fragmentation, sleep deprivation, and the known sequelae of disturbed sleep architecture, including associated daytime tiredness and alterations in normal behavior patterns. Nasal obstruction may produce greater physiologic effects during sleep than during the awake state. A complete examination of the upper respiratory tract should be done in all patients with obstructive sleep apnea and snoring. The degree of nasal obstruction is not directly correlated with the severity of symptoms and findings.

Humans↗

Uvulopalatopharyngoplasty for treatment of obstructive sleep apnea.

Currently, uvulopalatopharyngoplasty (UPPP) is the most common surgical procedure used for the treatment of obstructive sleep apnea. Patients with clinically significant obstructive sleep apnea in whom medical treatment has failed or who are unwilling to comply with medical therapy are considered candidates for UPPP. The initial surgical results obtained in nonselected patients with obstructive sleep apnea were highly variable, approximately half of the patients experiencing more than a 50% reduction in the frequency of disordered breathing events postoperatively. Although differences in surgical technique likely account for some of the variability, preoperative differences in the site (or sites) of upper airway collapse are also thought to influence the surgical results. Because UPPP involves resection of the uvula, distal margin of the soft palate, palatine tonsils, and any excessive lateral pharyngeal tissue, patients with anatomic narrowing and collapse confined to the velopharyngeal or retropalatal region of the upper airway are considered optimal surgical candidates. Fiberoptic pharyngoscopy, cephalometric roentgenography, computed tomography, and somnofluoroscopy are procedures that can be used preoperatively to help select optimal candidates for UPPP. The results suggest that the success rate of UPPP can approach 66% with careful preoperative selection of patients.

Evaluation Studies as Topic↗

Evaluation of masses in the neck.

A mass in the neck represents a diverse number of possible pathologic conditions. The importance of obtaining a thorough history and ensuring that a complete head and neck examination is performed has been emphasized. The physician should then be able to determine if the mass is insignificant and warrants observation or significant and warrants action. Physicians must determine, to the best of their abilities, that appropriate evaluation and treatment are done for the patient. Common errors should be avoided.

Diagnosis, Differential↗

Patterns of failure after total laryngectomy for glottic carcinoma.

The 136 patients who underwent total laryngectomy as the primary treatment for squamous cell carcinoma of the glottis at the Mayo Clinic in 1970 through 1981 were followed by retrospective record review for at least 4 years or until death, local recurrence, neck recurrence, or delayed neck metastasis. Cancer recurred or progressed in a previously untreated area in 35 patients; for the 29 affected above the clavicles, the median time to manifestation was 9.9 months. A Cox model with four risk factors (P less than 0.05) was found to predict failure above the clavicles: lymph node metastasis in the laryngectomy specimen (Delphian, pretracheal, tracheoesophageal, parathyroid), primary tumor more than 1.5 cm in greatest diameter, subglottic extension, and lymph node metastasis in the neck dissection specimen. A simple risk score computed from the Cox model shows that the more factors present, the higher the risk of disease progression or recurrence.

Adult↗

Correlation of interleukin-1 beta and cachectin concentrations in cerebrospinal fluid and outcome from bacterial meningitis.

Because interleukin-1 beta (IL-1 beta) and cachectin (tumor necrosis factor) are thought to mediate the body's response to microbial invasion, we measured IL-1 beta and tumor necrosis factor concentrations in paired cerebrospinal fluid (CSF) samples (on admission to the hospital, CSF1; 18 to 30 hours later, CSF2) from 106 infants and children with bacterial meningitis. In CSF1, IL-1 beta was detected in 95% of samples; the mean (+/- 1 SD) concentration was 944 +/- 1293 pg/ml. Patients with CSF1 IL-1 beta concentrations greater than or equal to 500 pg/ml were more likely to have neurologic sequelae (p = 0.001). Tumor necrosis factor was present in 75% of CSF1 samples; the mean concentration was 787 +/- 3358 pg/ml. In CSF2 the mean IL-1 beta concentration was 135 +/- 343 pg/ml, and IL-1 beta concentrations correlated significantly with CSF2 leukocyte count, with glucose, lactate, protein, and tumor necrosis factor concentrations, and with neurologic sequelae. Tumor necrosis factor was detected in CSF2 specimens of 53 of 106 patients, with a mean concentration of 21 +/- 65 pg/ml. Of the 106 patients, 47 received dexamethasone therapy at the time of diagnosis. These patients had significantly lower concentrations of IL-1 beta and higher glucose and lower lactate concentrations in CSF2, and they had a significantly shorter duration of fever compared with the values in patients not treated with steroids (p less than or equal to 0.002). Our data suggest a possible role of IL-1 beta and tumor necrosis factor as mediators of meningeal inflammation in patients with bacterial meningitis, and might explain, in part, the beneficial effect of dexamethasone as adjunctive treatment in this disease.

Bacterial Infections↗

Obstructive sleep apnea syndrome in patients with class II malocclusion.

This study was designed to analyze the effect of class II malocclusion as a factor in the development of obstructive sleep apnea syndrome. Although mandibular retrusion has been reported coincidentally with obstructive sleep apnea syndrome many times, no causal relationship has been established. No previous study has analyzed the occurrence of obstructive sleep apnea syndrome in patients with class II malocclusion without sleep complaints. In this study, we selected 12 patients with class II malocclusion who required surgical mandibular-lengthening or repositioning procedures. These patients were surveyed for sleep habits or sleep complaints and then studied with overnight polysomnography for sleeping or breathing abnormalities. None of these patients had obstructive sleep apnea syndrome. From this sample population, an incidence of obstructive sleep apnea syndrome of no more than 26.5% in the surgical population of patients with class II malocclusion can be extrapolated.

Adolescent↗

Induction of meningeal inflammation by outer membrane vesicles of Haemophilus influenzae type b.

Haemophilus influenzae type b (Hib) lipooligosaccharide (LOS) induces meningitis in an established rabbit model of experimental meningitis. To evaluate the inflammatory ability of Hib LOS in its native state as part of outer membrane of Hib, the CSF inflammatory response to Hib outer membrane vesicles (OMV) was compared with that produced by Hib LOS. A significant dose-dependent meningeal inflammatory response, as evidence by increased concentrations of white blood cells and protein and lactate concentration in CSF, was found after intracisternal injection of Hib OMV containing 0.02-200 ng of LOS. On a LOS weight basis, purified LOS and LOS in OMV did not differ significantly with regard to the CSF inflammatory response. Preincubation of Hib OMV with monoclonal antibodies directed against cell surface-exposed epitopes on Hib LOS did not affect the inflammatory ability of OMV, whereas preincubation of OMV with polymyxin B significantly reduced both pleocytosis and lactate concentration. Thus, Hib OMV represents a relevant nonreplicating vehicle in which Hib LOS might interact with CNS tissues to produce meningitis.

Analysis of Variance↗

Tumor necrosis factor in mediating experimental Haemophilus influenzae type B meningitis.

Tumor necrosis factor (TNF) could possibly be instrumental in mediating injury to the CNS during bacterial meningitis. In CSF of rabbits with meningitis induced with Haemophilus influenzae type b (Hib) lipooligosaccharide (LOS), TNF activity was first detected 45 min after intracisternal (IC) injection of 20 ng Hib LOS and white blood cells (WBC) first appeared 75 min later. The peak TNF activity (45 ng/ml) was observed at 120 min after IC and persisted for 5 h. When 1-2 X 10(7) CFU of Hib was used to induce meningitis, peak CSF TNF activity was comparable with that after 20 ng Hib LOS, but the activity persisted for 14 h. Dexamethasone (DXM) (1 mg/kg per i.v.) given 1 h before or simultaneously with IC Hib LOS reduced significantly TNF activity and meningeal inflammation. Goat anti-human TNF alpha antibodies given IC with 20 ng Hib LOS or 2 X 10(6) CFU of Hib resulted in a significant reduction in CSF TNF concentrations, which was also associated with reduced meningeal inflammation in Hib LOS-inoculated animals. We conclude that TNF participates in mediating meningeal inflammation associated with Hib experimental meningitis, and that DXM, when given before or with Hib LOS, inhibits CSF TNF production and modulates the meningeal inflammatory response.

Animals↗

Utility of near-total laryngectomy for supraglottic, pharyngeal, base-of-tongue, and other cancers.

This report emphasizes the utility of the near-total laryngectomy for those patients in whom conventional conservation surgery is an option but may be oncologically or physiologically unsafe. The near-total operation can be offered for supraglottic cancer, pharyngeal cancer, and, more commonly, primary glottic cancer with cord fixation. Its application is described for patients who are candidates for conventional conservation surgery but are compromised physiologically by age or poor general health and for patients in whom tumor extent would not permit safe conventional conservation surgery.

Adult↗

High-grade carcinoma of the oral cavity.

High-grade carcinoma of the oral cavity is considered to be an aggressive malignancy associated with a poor prognosis. The tumors are often considered to be relatively radiosensitive. Because previous reviews of oral cavity cancer have contained few patients with grade 4 lesions, little is known about the true behavior of these tumors. Information was collected on 80 patients with high-grade carcinoma of the oral cavity to determine the clinical findings and optimal treatment of this tumor. Primary tumor location, presence of neck metastasis, and clinical stage did not affect survival. Tumor size was a significant risk factor. The 5-year survival rate for patients with high-grade carcinoma treated by combination surgery and radiation (52%) was significantly greater (p less than or equal to 0.05) than that for patients treated by radiation alone (28%) or surgery alone (24%). This study is the first to describe the clinical course of a large number of patients exclusively with high-grade carcinoma of the oral cavity.

Adult↗

Lymphoepithelioma of the oropharynx.

Lymphoepithelioma is common in the nasopharynx, but its presence elsewhere in Waldeyer's ring is rare. Thirteen patients with lymphoepithelioma in the tonsil and base of the tongue have been treated at our institution. At initial examination, all 13 patients had advanced clinical disease. Five years after their initial treatment, seven patients were alive and free of disease. Radiation therapy controlled local and regional disease in 10 (77%) patients, yet three of these died of distant metastasis. Patients with lymphoepithelioma have a significantly better prognosis (p less than 0.05) than do patients with either nonkeratinizing or keratinizing high-grade oropharyngeal carcinoma. Early recognition and combined therapy may further improve the prognosis. Differentiation of lymphoepithelioma from other high-grade squamous cell carcinomas of the oropharynx is important to guide treatment and to provide prognostic information.

Adult↗

Cerebrospinal fluid interleukin 1-beta and tumor necrosis factor concentrations and outcome from neonatal gram-negative enteric bacillary meningitis.

Concentrations of interleukin 1-beta and tumor necrosis factor in cerebrospinal fluid (CSF) of 42 neonates with Gram-negative enteric bacillary meningitis were determined and correlated with outcome and other CSF indices. At the time of diagnosis interleukin 1-beta was detected in CSF of 40 infants and peak concentrations correlated significantly with outcome from disease. Days of interleukin 1-beta concentrations of greater than 200 pg/ml or greater than or equal to 20 pg/ml were significantly correlated with days that CSF cultures were positive and that K1 antigen and endotoxin were detected in CSF. Tumor necrosis factor activity was detected in CSF of 25 of 27 infants; there was no correlation between outcome and CSF tumor necrosis factor concentrations. The results provide a possible rationale for therapeutic intervention to improve outcome.

Enterobacteriaceae Infections↗