CD117 (c-KIT) overexpression in patients with extensive-stage small-cell lung carcinoma.

BACKGROUND: The aim of this study was to determine the incidence and role of CD117 (c-KIT) overexpression as a predictive/prognostic marker in extensive-stage small-cell lung carcinoma (ESSCLC). We performed a retrospective study on subjects with a biopsy-proven diagnosis of ESSCLC. PATIENTS AND METHODS: A chart review for demographic and clinical data was performed on patients with ESSCLC diagnosed between 1991 and 2001. CD117 overexpression was evaluated using immunohistochemistry (A4052 polyclonal antibody) performed on archival paraffin-embedded specimens. RESULTS: Two hundred and twenty-three patients with ESSCLC were identified, of whom 193 (84 females, 109 males) with a mean age of 68.5 years (range 42-90) had adequate tissue specimens available for CD117 testing. The most commonly presenting symptom was weight loss, seen in 61 patients (31.6%). Of the 193 specimens, 54 (27.9%) showed CD117 overexpression. The median length of survival for CD117-positive patients was 9 months as compared with the CD117-negative population, in whom the survival was 6 months (P = 0.025, Cox proportional hazard method). CONCLUSIONS: CD117 overexpression detected using immunohistochemistry is observed in about a third of patients with ESSCLC and does not have statistically significant prognostic value. However, CD117 may be a potential target for site-specific immunotherapy in ESSCLC. Our findings suggest a role for clinical trials assessing the role of selective tyrosine kinase inhibitor STI-571 (alone or in combination with conventional therapy) in patients with ESSCLC.     

Detection of natural and induced phenoloxidase activities in human serum

Natural and induced phenoloxidase activities were detected in human serum using nine different phenolic substrates, namely, tyrosine, tyramine, L-DOPA, DL-DOPA, dopamine, catechol, hydroquinone, protocatechuic acid and pyrogallol. Phenoloxidase activity was induced anew in serum using exogenous elicitors, such as proteases or detergents. Among the proteases and detergents tested, pronase, SDS and Tween 20 were the best elicitors of phenoloxidase activities in serum, wherein, hydroquinone was the best phenolic substrate for both untreated as well as pronase treated serum and SDS or Tween 20 treated serum resulted in highest oxidation of dopamine or tyrosine, respectively. In the present study, all these oxidative reactions were inhibited by phenoloxidase inhibitors, namely, PTU and tropolone, thereby, confirming the role of phenoloxidase in human serum.     

Excessive neutrophils and neutrophil extracellular traps contribute to acute lung injury of influenza pneumonitis

Complications of acute respiratory distress syndrome (ARDS) are common among critically ill patients infected with highly pathogenic influenza viruses. Macrophages and neutrophils constitute the majority of cells recruited into infected lungs, and are associated with immunopathology in influenza pneumonia. We examined pathological manifestations in models of macrophage- or neutrophil-depleted mice challenged with sublethal doses of influenza A virus H1N1 strain PR8. Infected mice depleted of macrophages displayed excessive neutrophilic infiltration, alveolar damage, and increased viral load, later progressing into ARDS-like pathological signs with diffuse alveolar damage, pulmonary edema, hemorrhage, and hypoxemia. In contrast, neutrophil-depleted animals showed mild pathology in lungs. The brochoalveolar lavage fluid of infected macrophage-depleted mice exhibited elevated protein content, T1-α, thrombomodulin, matrix metalloproteinase-9, and myeloperoxidase activities indicating augmented alveolar-capillary damage, compared to neutrophil-depleted animals. We provide evidence for the formation of neutrophil extracellular traps (NETs), entangled with alveoli in areas of tissue injury, suggesting their potential link with lung damage. When co-incubated with infected alveolar epithelial cells in vitro, neutrophils from infected lungs strongly induced NETs generation, and augmented endothelial damage. NETs induction was abrogated by anti-myeloperoxidase antibody and an inhibitor of superoxide dismutase, thus implying that NETs generation is induced by redox enzymes in influenza pneumonia. These findings support the pathogenic effects of excessive neutrophils in acute lung injury of influenza pneumonia by instigating alveolar-capillary damage.     

Antrochoanal Polyp Presenting as Obstructive Sleep Apnea

Antrochoanal polyps (ACPS) are uncommon in children presenting to the pediatric clinic. They commonly present with unilateral nasal obstruction. ACPS presenting as obstructive sleep apnea (OSA) in a young child is an uncommon initial presentation. A high level of suspicion is needed to diagnose OSA in young children as the presenting symptoms may be nonspecific and sometimes misleading.     

Uvulopalatopharyngoplasty in the Management of Obstructive Sleep Apnea: The Mayo Clinic Experience

OBJECTIVE: To assess the role of uvulopalatopharyngoplasty (UPPP) in the treatment of obstructive sleep apnea (OSA) using polysomnography (PSG) data within 6 months before and after surgery.PATIENTS AND METHODS: We analyzed PSG and body mass index (BMI) data from patients with OSA who were 18 years or older and who underwent UPPP between January 1, 1988, and August 31, 2006.RESULTS: Sixty-three patients (51 men [81.0%]; mean ± SD age, 42.1±13.9 years; mean ± SD BMI, 34.9±7.2) underwent PSG a mean ± SD of 50±47 days before and 88.5±34.0 days after UPPP. Surgical cure was defined as a postoperative apnea-hypopnea index (AHI) of 5 or less. Fifteen patients (24%) achieved a surgical cure. Twenty-one patients (33%) had a postoperative AHI of 10 or less, whereas 32 (51%) achieved a 50% or greater reduction in AHI and/or an AHI of 20 or less. No significant changes were noted in BMI before and 6 months after UPPP. Patients who attained an AHI of 5 or less were younger (mean ± SD age, 35.9±13.1 vs 44±13.7 years; P=.05), had lower BMIs (mean ± SD, 30.8±6.5 vs 34.6±6.6; P=.05), and had less severe OSA (mean ± SD AHI, 38.1±33.6 vs 69.6±32.8; P=.004). Of the 48 patients (76%) with a post-UPPP AHI greater than 5, 35 (56%) received continuous positive airway pressure, with a mean reduction in pressure of 1.4 cm H₂O (95% confidence interval, -0.4 to -2.4 cm H₂O).CONCLUSION: Independent of changes in BMI, in our retrospective analysis, UPPP achieved an AHI of 5 or less in 24% and an AHI of 10 or less in 33% of patients with OSA who underwent PSG 6 months before and after surgery. In those with residual OSA who received continuous positive airway pressure, the required pressure setting decreased by 1.4 cm H₂O.AHI = apnea-hypopnea index; BMI = body mass index; CPAP = continuous positive airway pressure; OSA = obstructive sleep apnea; PSG = polysomnography; UPPP = uvulopalatopharyngoplastyObstructive sleep apnea (OSA) is highly prevalent, affecting 4% of men and 2% of women who meet a disease-defining threshold of at least 5 episodes of apnea or hypopnea per hour of sleep (apnea-hypopnea index [AHI] ≥5) and excessive daytime sleepiness.¹ Continuous positive airway pressure (CPAP), a technique that pneumatically supports the upper airway, is a therapeutic mainstay for OSA. It has been shown to reduce the AHI, improve sleepiness and quality of life, and reduce cardiovascular risk.^2,3 Despite demonstrable benefits and technological equipment advances, compliance with CPAP therapy varies, with 29% to 83% of patients using CPAP for less than 4 hours a night in various studies.⁴ Accordingly, physicians may recommend other options for their patients with OSA, including risk factor modification such as weight loss, oral appliances that advance the mandible or tongue during sleep,⁵ or a variety of surgical procedures to bypass or expand the upper airway.⁶The most common surgical procedure performed for OSA is uvulopalatopharyngoplasty (UPPP).^7,8 Introduced by Fujita et al⁹ in 1981, UPPP involves tonsillectomy (if not previously performed), trimming and reorientation of the posterior and anterior tonsillar pillars, and excision of the uvula and posterior palate. Often, UPPP is combined with other nasopharyngeal or oropharyngeal procedures. The reported success of UPPP as a treatment of OSA is between 16% and 83%, depending on the definition of a positive outcome.^7,10 Some authors have defined surgical success or cure after UPPP as a 50% reduction in the AHI, whereas others combine this criterion with an absolute AHI of 20 or less.^11-14 Unfortunately, use of these criteria means that successfully treated patients may still have mild to moderate residual OSA. Increasing evidence shows that, when treating OSA, reducing the AHI to less than 5 is necessary to improve health care-related outcome measures, such as hypertension.¹⁵ Accordingly, there have been calls for caution about UPPP as first-line therapy for OSA and for all future studies of UPPP to base surgical success on AHI outcomes of 5 or less or 10 or less, targets typically expected from CPAP therapy.^7,16 Therefore, to better define response to UPPP, we reviewed the UPPP experience at Mayo Clinic''s site in Rochester, MN, using these more stringent and contemporary criteria.     

Reversal of Sleep-Disordered Breathing with Opioid Withdrawal

Obstructive sleep apnea, central sleep apnea, sleep related hypoventilation, Biot's or ataxic breathing, and cluster breathing are some of the commonly described sleep disorders in patients who are on long-term opioids. Continuous positive airway pressure that is commonly used to treat obstructive sleep apnea may not be effective in treating sleep-disordered breathing in long-term opioid users, and an adaptive servoventilator (ASV) may be needed. We present a 30-year-old woman with excessive daytime sleepiness and sleep-disordered breathing for the past 4 years. Medical history was complicated by chronic osteomyelitis, periorbital abscess, and chronic facial pain requiring methadone for pain control for the last 4 years. In this case, ASV, though effective, was not tolerable due to chronic facial pain, and successful withdrawal of methadone at our pain rehabilitation center resolved the sleep-disordered breathing and improved daytime sleepiness. This is to our knowledge the first case report of resolution of sleep-disordered breathing and improvement in daytime sleepiness after withdrawal of long-term opioid use.     

Effect of root canal debridement on inflammatory cytokine levels

In endodontic infections, inflammatory mediators such as cytokines are released, recruited and retained until the infection is eradicated. Root canal therapy is performed to prevent the spread of infection. The aim of this study was to investigate the effects of root canal debridement (cleaning and shaping) on periapical inflammation by measuring the levels of inflammatory cytokines, Interleukin‐8 (IL‐8) and Interleukin‐10 (IL‐10). The study includes twenty patients with pulp necrosis and asymptomatic apical periodontitis. Periradicular sample was collected using paper points before and after root canal debridement. Cytokine levels were determined by Sandwich Enzyme‐Linked Immunosorbent Assay (ELISA). Data were analysed using paired t‐test (PASW Statistics 18) (P = 0.05). All samples showed the presence of IL‐8 and IL‐10 prior to root canal debridement. Significantly reduced levels (P < 0.05) of IL‐8 and IL‐10 were detected after root canal debridement. In conclusion, root canal debridement significantly decreased the levels of the tested pro‐ and anti‐inflammatory cytokine in the periradicular interstitial fluid.