Nasal endoscopy score thresholds to trigger consideration of chronic rhinosinusitis treatment escalation and implications for disease control.

BACKGROUND: In the absence of direct evidence supporting how to use nasal endoscopy findings to judge chronic rhinosinusitis (CRS) disease control, experts' practice patterns could provide guidance. METHODOLOGY: Participants consisted of a diverse group of twenty-nine rhinologists. Participants were presented with every possible combination of bilateral nasal endoscopy findings represented by the modified Lund-Kennedy (MLK; range: 0-12) endoscopic scoring system and Nasal Polyp Score (NPS; range: 0-8). Reflecting the practical consequence of CRS disease control assessment, participants were asked whether they would consider CRS treatment escalation based on each scenario in the absence of any CRS symptoms, and how strongly they considered escalating therapy. The same scenarios were then presented in the context of 1 burdensome CRS symptom and participants again were asked whether they would consider treatment escalation. RESULTS: The median threshold total MLK score for considering treatment escalation was ≥4 and 75.9% of participants' MLK thresholds were within 1 point of 4. The median threshold total NPS for considering treatment escalation was ≥3 and 62.5% of participants' NPS thresholds were within 1 point of 3. Endoscopy score thresholds decreased in the presence of 1 burdensome symptom and generally increased when requiring stronger affirmation for considering CRS treatment escalation. CONCLUSION: Reflecting the practice patterns of a diverse group of rhinologists, MLK score ≥4 or NPS ≥3 may serve as thresholds for considering CRS treatment escalation. Alternatively, MLK score.

Correlation between extent of sinus surgery, radiographic disease, and postoperative outcomes.

BACKGROUND: The extent of endoscopic sinus surgery (ESS) required for optimal outcomes in chronic rhinosinusitis (CRS) is undefined. We evaluated whether concordance between the extent of surgery and degree of radiographic disease influences postoperative outcomes. METHODS: 247 CRS patients who underwent ESS were retrospectively assigned a concordance score reflecting the similarity between the extent of surgery and degree of radiographic disease. 0 points were assigned when sinusotomy was performed on a diseased sinus, or no sinusotomy was performed on a nondiseased sinus; plus 1 for sinusotomy on a nondiseased sinus; and -1 for a diseased sinus left unopened. The total possible score ranged from minus 10 to plus 10. Patients were divided into 5 subgroups according to variance from complete concordance. SNOT-22 scores and revision rates were compared at 6 and 24 months. RESULTS: All five subgroups had similar preoperative SNOT-22 scores and improved at 6 months postoperatively. At 6 months postoperatively, the most conservatively operated and most extensively operated subgroups each achieved equivalent improvements in SNOT-22 as the completely concordant subgroup. At 24 months, the most extensively operated subgroup had a 12.5-point smaller improvement in SNOT-22 scores compared to the completely concordant subgroup. Multivariate analysis showed no association between concordance score and revision rate. CONCLUSIONS: Symptom improvement and revision rates after ESS do not appear to correlate with the degree of concordance between extent of surgery and radiographic disease. More extensive surgery than indicated by CT confers neither greater symptomatic improvement nor long-term detriment.

Eckols reduce dental pulp inflammation through the ERK1/2 pathway independent of COX-2 inhibition.

OBJECTIVES: The aim of this study was to elucidate the role of 6-6 bieckol (EB1) and pholorofucofuroeckol-A (EB5) from brown seaweed marine algae (Eisenia bicyclis) on lipopolysaccharide (LPS)-induced inflammation in human dental pulp cells (HDPCs). METHODS: The cytotoxicity of EB1 and EB5 was examined by MTT assay on LPS-induced human dental pulp cells. Their role on expression of inflammatory, odontogenic, and osteogenic molecules was determined by Western blot analysis. The dentin mineralization was checked by alkaline phosphatase activity. RESULTS: The five compounds from E. bicyclis have different structure with non-cytotoxic in HDPCs. EB1 and EB5 showed anti-inflammatory properties and inhibited phosphorylated-extracellular signal-regulated kinase (p-ERK1/2) and phosphorylated-c-jun N-terminal kinases (p-JNK) without any cytotoxicity. In particular, EB1 inhibited cyclooxygenase-2 (COX-2) and p-ERK1/2 signaling, and EB5 inhibited only p-ERK1/2 signaling but not COX-2. Both compounds inhibited nuclear factor kappa-B (NF-κB) translocation. Furthermore, EB1 and EB5 increased dentinogenic and osteogenic molecules, and dentin mineralized via alkaline phosphatase activity (ALP) in LPS-induced HDPCs. CONCLUSIONS: This study elucidates that EB1 and EB5 have different types of anti-inflammatory property and help in dentin formation. Therefore, these compounds derived from marine algae of E. bicyclis may be used as selective therapeutic strategies for pulpitis and oral diseases.

Flavonoid-Rich Fruit Intake in Midlife and Late-Life and Associations with Risk of Dementia: The Framingham Heart Study.

BACKGROUND: Fruits are an important source of flavonoids, and greater intake of dietary flavonoids in older adults has been shown to be associated with decreased risk of dementia. It is unclear whether this relationship is similar or different between younger adults and older adults. OBJECTIVES: We examined for associations between midlife and late-life intake of flavonoid-rich fruits and incident dementia. We hypothesized that greater total cumulative intake of flavonoid-rich fruits in midlife and late-life adults would be associated with reduced risk of all-cause dementia. DESIGN: Longitudinal, cohort study design. SETTING: Framingham Heart Study, which is a longitudinal, multi-generational community-based cohort based in Framingham, Massachusetts, USA. PARTICIPANTS: Participants from the Framingham Heart Study Offspring cohort were included (n = 2,790) who attended the fifth core exam between 1991 to 1995, and were dementia-free and at least 45 years of age at that time, as well as had valid food frequency questionnaires from the fifth to ninth core exams. MEASUREMENTS: Consumption of fruits with high flavonoid content or are important contributors to overall flavonoid intake was collected via food frequency questionnaire. Flavonoid-rich fruits from the food frequency questionnaire included raisins or grapes, prunes, bananas, fresh apples or pears, apple juice or cider, oranges, orange juice, grapefruit, grapefruit juice, strawberries, blueberries, and peaches, apricots, or plums. Dementia ascertainment was based on a multidisciplinary consensus committee, and included all-cause dementia and Alzheimer's disease dementia diagnoses based on research criteria. Cox models were used to examine associations between cumulative fruit intake and incident dementia, stratified by midlife (45-59 years; n = 1,642) and late-life (60-82 years; n = 1,148). RESULTS: Greater cumulative total fruit intake in midlife, but not late-life, was significantly associated with a 44% decreased risk of all-cause dementia (HR = 0.56; 95% CI = 0.32 - 0.98; p = 0.044). Decreased risk of all-cause dementia was also associated with higher intake of apples or pears in midlife and late-life, as well as higher intake of raisins or grapes in midlife only, and higher intake of oranges, grapefruit, blueberries, and peaches, apricots, or plums in late-life only. CONCLUSIONS: Among participants from the Framingham Heart Study, greater overall consumption of flavonoid-rich fruits in midlife was associated with reduced risk of dementia, though intake of specific fruits in midlife and late-life may have a protective role against developing dementia. These findings may help to inform future recommendations on when dietary interventions may be most beneficial to healthy brain aging across the life course.

Anti-inflammatory effect of pachymic acid promotes odontoblastic differentiation via HO-1 in dental pulp cells.

OBJECTIVES: Heme oxygenase-1 (HO-1) is contributed to odontoblast differentiation in human dental pulp cells (HDPCs). In this study, pachymic acid from mushroom Formitopsis niagra is examined to determine whether it affects pulpal inflammation and promotes odontogenesis via HO-1 gene expression. MATERIALS AND METHODS: The HDPCs were given H2O2 for inflammation. The anti-inflammatory character and odontoblast differentiation by pachymic acid were analyzed by Western blotting, alkaline phosphatase activity, and alizarin red S staining. To understand the mechanism of pachymic acid via HO-1 induction, the cells were treated with zinc protoporphyrin IX (ZnPP: HO-1 inhibitor). RESULTS: H2O2 induced pulp inflammation and disturbed odontoblast differentiation. However, the HDPCs treated with pachymic acid affected anti-inflammatory effect and induction of odontoblast differentiation through increasing HO-1 expression. In addition, pachymic acid has potent cytoprotection and mineralization under H2O2 treatment. Furthermore, pachymic acid significantly suppressed nuclear factor-kappa B (NF-κB) translocation into nucleus and induced NE-E2-related factor-2 (Nrf2) translocation into nucleus. Overall, NF-κB and Nrf2 translocation were regulated by the HO-1 pathway. CONCLUSIONS: The pachymic acid showed anti-inflammatory function and odontoblast differentiation via HO-1 pathway. These results suggested that pachymic acid may be applicable for prevention of oral inflammation or to improve dentin mineralization against several stresses.

PPARγ induces growth inhibition and apoptosis through upregulation of insulin-like growth factor-binding protein-3 in gastric cancer cells.

Peroxisome proliferator activator receptor-gamma (PPARγ) is a ligand-activated transcriptional factor involved in the carcinogenesis of various cancers. Insulin-like growth factor-binding protein-3 (IGFBP-3) is a tumor suppressor gene that has anti-apoptotic activity. The purpose of this study was to investigate the anticancer mechanism of PPARγ with respect to IGFBP-3. PPARγ was overexpressed in SNU-668 gastric cancer cells using an adenovirus gene transfer system. The cells in which PPARγ was overexpressed exhibited growth inhibition, induction of apoptosis, and a significant increase in IGFBP-3 expression. We investigated the underlying molecular mechanisms of PPARγ in SNU-668 cells using an IGFBP-3 promoter/luciferase reporter system. Luciferase activity was increased up to 15-fold in PPARγ transfected cells, suggesting that PPARγ may directly interact with IGFBP-3 promoter to induce its expression. Deletion analysis of the IGFBP-3 promoter showed that luciferase activity was markedly reduced in cells without putative p53-binding sites (-Δ1755, -Δ1795). This suggests that the critical PPARγ-response region is located within the p53-binding region of the IGFBP-3 promoter. We further demonstrated an increase in PPARγ-induced luciferase activity even in cells treated with siRNA to silence p53 expression. Taken together, these data suggest that PPARγ exhibits its anticancer effect by increasing IGFBP-3 expression, and that IGFBP-3 is a significant tumor suppressor.

Expression of the insulin-like growth factors (IGFs) and the IGF-binding proteins (IGFBPs) in human gastric cancer cells.

Insulin-like growth factor (IGF)-I and -II are potent mitogens and postulated to exert autocrine, and paracrine effects on growth regulation in human gastric cancer. Their mitogenic effects are tightly regulated by the IGF binding proteins (IGFBPs). In this study, we evaluated the mRNA expression of IGF-I, IGF-II and the IGFBPs in a panel of human gastric cancer cell lines, and normal and tumour tissue specimens from patients with gastric cancer by reverse transcriptase-polymerase chain reaction (RT-PCR) and competitive PCR. Conditioned media (CM) of the gastric cancer cell lines were studied for the secretion of the IGFBPs by western ligand blot (WLB) and western immunoblot (WIB). IGF-I and IGF-II were expressed in all of the gastric cancer cell lines, and the normal and tumour tissue specimens. Overexpression of the IGFs, in particular, IGF-II, was observed in the tumour tissues. The expression pattern of IGFBPs was heterogeneous among the gastric cancer cell lines. IGFBP-2 was expressed in all of the gastric cancer cell lines, whereas IGFBP-1 was not detected in any cell lines. IGFBP-4 was expressed in the most of cell lines. IGFBP-3, IGFBP-5 and IGFBP-6 were expressed in approximately 50% of cell lines. In addition, exogenous IGF-I and IGF-II stimulated the proliferation of gastric cancer cells, suggesting the existence of a functional IGF system in gastric cancer. Taken together, our data-suggest that the IGF-IGFBP system may play an important role in the initiation, progression and metastasis of gastric cancer. Further studies are needed to understand the exact role of IGFs and IGFBPs in gastric neoplasia.

Suppression of tumorigenicity and metastasis in B16F10 cells by PTEN/MMAC1/TEP1 gene.

PTEN/MMAC1/TEP1 (PTEN) is a tumor suppressor gene that is mutated in a variety of advanced and metastatic cancers, strongly suggests that PTEN alteration is possibly involved in the tumor progression and formation of metastases. However, the roles of PTEN in tumor growth and metastasis and its functional mechanisms are not fully understood. We evaluated the tumor suppressor function of PTEN gene on tumor growth and metastasis in vitro and in vivo. Our results of in vitro soft agar assay and in vivo PTEN-expressing tumor cell growth showed that PTEN inhibited the tumorigenicity of B16F10 melanoma cells. Anti-metastatic function of PTEN was also revealed by experimental pulmonary metastatic animal model. For the further insight into the mechanisms underlying the PTEN-mediated inhibition of tumor metastasis, we have examined the role of PTEN on the secretion of matrix metalloproteinases (MMPs), insulin-like growth factors (IGFs) and the expression of secretory and cellular vascular endothelial growth factor (VEGF) proteins that have been described to contribute to the metastasis of tumor. PTEN significantly lowered MMPs and IGFs secretion and also expression of secretory and cellular VEGF proteins. These results suggest that PTEN tumor suppressor protein inhibits tumorigenicity and metastasis through regulation of MMP, IGFs, and VEGF expression.

An outbreak of type A foodborne botulism in Taiwan due to commercially preserved peanuts.

Until recently, botulism was not recognized as an important public health problem in Taiwan. In 1986, an outbreak of type A foodborne botulism resulted in nine cases, two of them fatal. The vehicle in this outbreak was commercially preserved peanuts processed by an improperly equipped, unlicensed cannery. A single batch of peanuts was implicated; however, we could not determine why this particular batch was contaminated. Efforts to recall the product were hampered by a lack of distribution records. Mass media announcements were used to warn the public about the outbreak, and preliminary data suggest the ensuing publicity improved botulism surveillance. The local preference for low-acid preserved foods, increasing consumerism, the shortage of adequately trained inspectors are factors which probably contributed to this outbreak. Stricter enforcement of food sanitation policies are needed to meet the changing situation in Taiwan.

Collagen shield enhancement of topical dexamethasone penetration.

Collagen corneal shields were investigated as a vehicle for enhancing the ocular penetration of topical 0.1% dexamethasone alcohol in rabbit eyes. Four protocols were compared: a single dexamethasone drop, hourly drops, a 24-hour collagen shield presoaked in 0.1% dexamethasone, and a presoaked collagen shield followed by hourly drops. Dexamethasone concentrations in the cornea, aqueous, iris, and vitreous were measured by radioassay at six time intervals, and cumulative drug delivery over 6 hours was calculated for each tissue. Treatment with a presoaked collagen shield plus hourly drops resulted in peak and cumulative drug delivery to the cornea, aqueous, iris, and vitreous that was twofold to fourfold higher than delivery achieved with hourly drops alone. A presoaked shield by itself yielded equivalent or superior peak and cumulative drug delivery compared with a regimen of hourly drops. Collagen shields significantly enhance topical dexamethasone penetration and may be useful for maximizing the intraocular delivery of dexamethasone and for decreasing the required frequency of topical dexamethasone administration.

Lipoid meningitis due to aseptic necrosis of a free fat graft placed during neurotologic surgery.

We present two unusual cases of aseptic postoperative lipoid meningitis resulting from necrosis of a free fat graft placed into a skull base craniotomy defect. Two patients underwent translabyrinthine resection of acoustic neuroma and received abdominal fat grafts to ablate the surgical defect. Both patients presented postoperatively with persistent cerebrospinal fluid (CSF) wound leak and severe headache. Computed tomography demonstrated hydrocephalus and widely dispersed intracranial fat droplets throughout the CSF circulation. Both patients ultimately required CSF diversion for management of persistent communicating hydrocephalus. The clinical and radiographic correlates of lipocephalus and lipoid meningitis are presented, and a review of free fat graft physiology is discussed.

Enlargement of the cochlear aqueduct: fact or fiction?

Enlargement of the cochlear aqueduct (CA) is often mentioned in the otologic literature, usually in its purported association with sensory hearing loss, stapes gusher, and transotic cerebrospinal fluid leak. In CT scans of 100 ears, the diameter of the CA medial aperture was found to be highly variable, ranging from 0 to 11 mm, with a mean of 4.5 mm. In contrast, the otic capsule segment was very narrow in every case. It could be visualized in only 56% of cases, none of which exceeded 2 mm in diameter. Several published reports of supposed CA enlargement presented images of a dilated medial aperture that was well within the range of normal variability according to the present study. In a thorough review of the literature on radiology of the CA, we were unable to find a single published image that convincingly demonstrated enlargement of the otic capsule portion. As radiographic CA enlargement has not been convincingly reported to date, it appears to be an exceedingly rare or perhaps even nonexistent malformation. It is important to recognize than even a radiographically normal CA may be hyperpatent. It is theoretically possible for increased fluid flow to result from either deficiencies in intraluminal membrane baffles or subtle canal enlargement beneath the resolution limits of CT scanning. However, as fluid flow through a tube is regulated by its narrowest point, it is extremely improbable that stapes gusher, transotic CSF leak, and vigorous perilymphatic fistula are generated by the CA when CT scans show any portion of it to be very narrow. A substantial body of evidence points to a deficient partition between the internal auditory canal and inner ear as causative in such cases. We propose that the criteria for the diagnosis of CA enlargement on high-resolution CT scan be a diameter exceeding 2 mm throughout its course from the posterior fossa to the vestibule.

Endoscopic septoplasty: indications, technique, and results.

Endoscopic septoplasty is an attractive alternative to traditional "headlight" approaches to septoplasty. The primary advantage of the technique is the ability to reduce morbidity and postoperative swelling in isolated septal deviations by limiting the dissection to the area of the deviation. This ability to markedly reduce the extent of subperichondrial dissection is particularly valuable in patients who have undergone prior septal cartilage resection. Other advantages include improved visualization, particularly in posterior septal deformities; improved surgical transition between septoplasty and sinus surgery; and its use as an effective teaching tool. We present our experience with endoscopic septoplasty in a series of 111 patients. Surgical indications, technique, and complications are discussed.

Attitudes, knowledge, and practices of otolaryngologists treating patients infected with HIV.

The AIDS epidemic has become one of the most important public health problems of this century. As the prevalence of HIV infection continues to rise, health care practitioners in all geographic regions can expect greater clinical exposure to patients infected with HIV. We conducted an anonymous survey of all practicing otolaryngologists in Ohio and California to investigate regional differences in attitudes, knowledge, and practices regarding the care of patients infected with HIV. We also examined the data with respect to year of completion of residency training to identify differences in attitudes or practices among otolaryngologists who trained in the era of AIDS (post-1982 graduates) in comparison with their predecessors (pre-1982 graduates). In comparison with Ohio otolaryngologists, California otolaryngologists reported more frequent clinical encounters with HIV-infected patients and displayed significantly better knowledge regarding the otolaryngologic aspects of HIV infection. Californians were more likely to support the right of an HIV-infected physician to maintain an unrestricted practice and would be less likely to disclose their HIV status to their patients and hospital if they were to become infected with HIV. Post-1982 graduates had more frequent encounters with HIV-infected patients than did pre-1982 graduates and demonstrated a better fund of knowledge. Although Californians were more likely than Ohioans to routinely double glove in surgery, the overall double gloving rate was low at 21%. Californians were no more likely than Ohioans to routinely use protective eyewear, water-impervious gowns, or indirect instrument-passing techniques in surgery. No differences were observed in prevalence of protective surgical precautions between pre-1982 and post-1982 graduates.(ABSTRACT TRUNCATED AT 250 WORDS)

Changes of tetanus specific IgG, IgM and IgG subclasses after DPT vaccination.

We evaluated tetanus specific IgG, IgM, IgG subclasses after DPT vaccination in infants and children. Tetanus toxoid specific IgG, IgM IgG subclasses were measured to characterize the isotope profile of antibody against tetanus toxoid. The values of the tetanus specific IgG in the positive group were significantly increased compared to those of the control group, and were significantly increased after two inoculation. Tetanus specific IgG was very low in adults and neonates. In our tetanus specific IgG subclasses study, forty-five of 56 cases (80%) showed predominantly IgG1 antibody responses to tetanus toxoid, while twenty-five of 56 cases (45%) showed IgG4 responses. Both IgG1 and IgG4 responses were demonstrated in 17 cases (30%). So we suggest that IgG was mainly involved in humoral immune response after DPT vaccination, and IgG1 may play an important role among IgG subclasses. IgG4, alone or together with IgG1, can also play a role in immune response to tetanus toxoid.

Medical therapy of acute and chronic frontal rhinosinusitis.

Despite innovations in surgical treatment of frontal sinus disease, medical therapy continues to be important. Preoperative, perioperative, and postoperative considerations are discussed. Diagnostic criteria, microbiology, and complications associated with frontal rhinosinusitis are also reviewed.

The five year experience with endoscopic trans-septal frontal sinusotomy.

Endoscopic trans-septal frontal sinusotomy (TSFS) represents a unique surgical approach to the floor of the frontal sinus. Although the final result can have similarities to the modified Lothrop procedure in that the intersinus septum may be drilled out, endoscopic TSFS represents a novel approach that can be valuable in patients with certain anatomic configurations. Endoscopic TSFS represents an alternate approach to the frontal sinus that may be used by the experienced endoscopist to augment treatment of refractory frontal sinus disease. This procedure is best considered for patients with favorable anatomy who have significant frontal sinus disease and cannot be managed adequately through an endoscopic frontal sinusotomy.

PPARγ induces growth inhibition and apoptosis through upregulation of insulin-like growth factor-binding protein-3 in gastric cancer cells

Peroxisome proliferator activator receptor-gamma (PPARγ) is a ligand-activated transcriptional factor involved in the carcinogenesis of various cancers. Insulin-like growth factor-binding protein-3 (IGFBP-3) is a tumor suppressor gene that has anti-apoptotic activity. The purpose of this study was to investigate the anticancer mechanism of PPARγ with respect to IGFBP-3. PPARγ was overexpressed in SNU-668 gastric cancer cells using an adenovirus gene transfer system. The cells in which PPARγ was overexpressed exhibited growth inhibition, induction of apoptosis, and a significant increase in IGFBP-3 expression. We investigated the underlying molecular mechanisms of PPARγ in SNU-668 cells using an IGFBP-3 promoter/luciferase reporter system. Luciferase activity was increased up to 15-fold in PPARγ transfected cells, suggesting that PPARγ may directly interact with IGFBP-3 promoter to induce its expression. Deletion analysis of the IGFBP-3 promoter showed that luciferase activity was markedly reduced in cells without putative p53-binding sites (-Δ1755, -Δ1795). This suggests that the critical PPARγ-response region is located within the p53-binding region of the IGFBP-3 promoter. We further demonstrated an increase in PPARγ-induced luciferase activity even in cells treated with siRNA to silence p53 expression. Taken together, these data suggest that PPARγ exhibits its anticancer effect by increasing IGFBP-3 expression, and that IGFBP-3 is a significant tumor suppressor.