[Analysis of risk factors and consequences for concurrent obstructive sleep apnea in chronic obstructive pulmonary disease patients].

Objective: To compare clinical characteristics between patients with chronic obstructive pulmonary disease (COPD) and COPD -OSA overlap, and to analyze the risk factors for OSA in patients with COPD. Methods: A total of 431 patients with COPD were divided into a COPD-OSA group with AHI>15 events/h or a COPD group with AHI ≤ 15 events/h according to the results of polysomnography, and their clinical characteristics were summarized. Risk factors for OSA overlap in COPD patients were identified by univariate and multivariate logistic regression analyses. Results: There were no significant differences in gender composition, dyspnea scale (mMRC) score, the numbers of acute exacerbations and hospitalizations in the last year, prevalence of coronary heart disease, or cor pulmonale or diabetes mellitus in the two groups (all P>0.05). Age, BMI, neck circumference, smoking index, COPD assessment test (CAT) score, the values of FEV(1) or FEV(1)%, FEV(1)/FVC ratios, and the prevalence of hypertension in the COPD-OSA group with AHI>15 events/h were significantly higher than in the COPD group with AHI ≤15 events/h, while the duration of COPD and the proportion of severe COPD were lower than the COPD group with AHI≤ 15 (P<0.05). The scores of Charlson Comorbidity Index, Epworth Sleepiness Scale (ESS) and Sleep Apnea Clinical Score (SACS) in the COPD-OSA group were significantly higher than in the COPD group with AHI≤ 15, with all P values<0.05. Risk factors for AHI>15 OSA coinciding in patients with COPD included BMI, neck circumference, ESS, SACS and CAT (P<0.05). Furthermore, BMI, ESS and CAT were independent risk factors for OSA in COPD patients (P<0.05). Compared with mild or moderate COPD cases, patients with severe COPD (FEV(1)%<50%) had a lower risk of having OSA (ß=-0.459, OR=0.632, 95% CI 0.401-0.997, P=0.048). Conclusions: Compared to COPD patients with AHI ≤ 15 events/h, OSA-COPD overlap patients (AHI>15 events/h) had a worse quality of life, more daytime sleepiness and higher prevalence of hypertension. BMI, ESS and CAT were independent risk factors for AHI>15 OSA in patients with COPD. The risk of having OSA in severe COPD patients was lower than cases with mild or moderate COPD.

[Treatment of intractable aspiration after partial laryngectomy by cuffed tracheostomy tube with inner cannula].

Objective: To evaluate the efficacy of cuffed tracheostomy tube with inner cannula for the treatment of intractable aspiration after partial laryngectomy. Methods: From May 2010 to June 2015, 15 patients with intractable aspiration after partial laryngectomy of laryngeal and hypopharyngeal carcinoma were enrolled. Cuffed tracheostomy tube with inner cannula was used in the 15 patients for treatment of intractable aspiration. The patients and their family were trained to manage the cuffed tracheostomy tube with inner cannula and to eat since the 14th day after surgery. Cuff was initially inflated with 10 ml air and then deflated of 0.5 ml air every 2-3 days. Until the inflation of cuff was no longer required, the cuffed tracheostomy tube was replaced by metal tracheostomy tube. The patients' swallowing function and aspiration were evaluated 6 months after treatment. Results: The 15 cases with intractable aspiration were treated with cuffed tracheostomy tube with inner cannula and after 2-3 months, 14 of them replaced the cuffed tracheostomy tubes with inner cannula by metal tracheostomy tubes and recovered oral eating, and tracheostomy tubes were no longer required for 12 of 14 patients in following 3-6 months, showing a total decannulation rate of 80% in the patients with refractory aspiration. Conclusion: It was safe and effective to treat aspiration after laryngeal and hypopharyngeal surgery with cuffed tracheostomy tube with inner cannula.

Modulation of epidermal growth factor receptors by retinoic acid in ME180 cells.

Retinoic acid (RA) increases epidermal growth factor (EGF) receptors in many cells; in ME180 cells, a human epidermoid carcinoma, RA resulted in a dose- and time-dependent reduction of EGF binding. In RA-treated ME180 cells, binding was 41% of the control. The reduction of EGF binding was due to a decrease in the number of receptors, from 8.7 x 10(4) to 3.6 x 10(4) per cell. The difference was present 8 h after the addition of RA and was reversible 3 days after its removal. Scatchard analysis indicated that RA did not change the binding affinity of EGF (Kd = 1 nM). Also, RA did not alter the rate of EGF internalization or the down-regulation induced by exogenous EGF. Flow-cytometric analysis revealed that RA did not alter the cell cycle. Soluble cell membrane extracts were prepared in a Tris buffer with protease inhibitors, immunoprecipitated, electrophoresed, and immunoblotted with an antiserum to EGF receptors. The EGF receptor band of Mr 170,000 was decreased in RA-treated cells. These results suggest that RA reduces the synthesis of EGF receptors in ME180 cells.

Inhibition of ornithine decarboxylase activity and cell proliferation by ultraviolet B radiation in EGF-stimulated cultured human epidermal keratinocytes.

Irradiation of EGF-stimulated human keratinocytes in vitro with ultraviolet B (UVB) radiation inhibited both ornithine decarboxylase (ODC) activity and cellular proliferation. A dose-dependent reduction in ODC activity occurred in primary cultures of adult facial keratinocytes and neonatal foreskin keratinocytes, and in an SV40-transformed keratinocyte cell line derived from neonatal foreskin. When SV40-transformed keratinocytes were treated with epidermal growth factor (EGF), ODC activity was induced up to 21 times in the absence of ultraviolet radiation. However, pre-treatment with UVB significantly reduced the EGF induction of ODC. For example, 85% less ODC activity was observed in cultures treated with EGF (10 ng/ml) plus 2.5 mJ/cm2 of UVB than cultures treated with EGF alone. To assess the effect of UVB on cell proliferation, normal human epidermal keratinocytes grown in medium containing EGF were irradiated with 5 and 10 mJ/cm2 UVB. At days 3 and 5 post-irradiation a significant (up to 78%) decrease in proliferation was observed. Nevertheless, the mean proportion of viable to dead cells remained similar in both UVB-treated and non-irradiated cell cultures. Northern blot analysis of total RNA isolated from irradiated and sham-irradiated cultures showed that UVB caused approximately a one third reduction in steady-state ODC mRNA levels in EGF-stimulated keratinocyte cultures. Because ODC is an enzyme required for cell proliferation, we propose that the UVB-induced decrease in cell proliferation may result at least in part from UVB inhibition of ODC mRNA accumulation and reduced enzyme activity.

Efficacy of enhanced external counterpulsation in the treatment of angina pectoris.

Eighteen patients with chronic angina despite surgical and medical therapy were treated with an improved system of enhanced external counterpulsation (EECP) (1 hour daily for a total of 36 hours). Patients underwent a baseline treadmill thallium-201 stress test. After EECP treatment, a thallium stress test was repeated for the same exercise duration. One week after treatment, patients also underwent a maximal stress test. All patients improved in anginal symptoms and generally decreased antianginal medications, with 16 obtaining complete relief from angina. Pre- and post-thallium stress testing performed for the same duration showed complete resolution of ischemic defects in 12 patients (67%), reduction in the area of ischemia in 2 (11%), and no change in 4 (22%). Thus, a decrease in myocardial ischemia was observed in 14 patients (78%; p less than 0.01). The exercise duration of maximal stress testing after EECP significantly improved from 8.14 +/- 0.71 to 9.72 +/- 0.77 minutes (p less than 0.005), although the double product did not change significantly. Analysis of these 2 tests in the subgroup of 14 patients with improvement in thallium studies showed significant increases in both exercise duration (8.58 +/- 0.66 to 10.44 +/- 0.59 minutes; p less than 0.001) and double product (21,827 +/- 2,044 to 24,842 +/- 1,707 mm Hg.beats/min; p less than 0.01). The improvement in reperfusion defects and increase in exercise duration are reflections of improved perfusion to ischemic regions of the myocardium. EECP uses additional thigh balloons and sequenced balloon inflation, effecting a significant increase in diastolic augmentation over previously available methods.(ABSTRACT TRUNCATED AT 250 WORDS)

Can angiographic findings predict which coronary patients will benefit from enhanced external counterpulsation?

Enhanced external counterpulsation is an effective treatment for chronic angina. Theoretical considerations predict greatest benefit in patients with at least 1 patent conduit in this group of 50 patients (all of whom improved clinically). Improvement in radionuclide stress perfusion imaging was seen in 80% of treated patients and was inversely related to extent of coronary disease.

Caffeic acid phenethyl ester inhibits proliferation of human keratinocytes and interferes with the EGF regulation of ornithine decarboxylase.

Caffeic acid phenethyl ester (CAPE) was evaluated for its potential in regulating keratinocyte proliferation. CAPE inhibited the proliferation of SV40 transformed keratinocytes (Z114) in a concentration- and time-dependent manner. Inhibition by CAPE was seen with 0.5 to 5.0 micrograms/ml at 48 h. Cell toxicity was observed at 10 micrograms/ml by changes in morphology and decreased viability. Pretreatment of Z114 cells with CAPE significantly prevented the full induction of ornithine decarboxylase (ODC) by epidermal growth factor (EGF) in a concentration- and time-dependent manner. Inhibition was observed with a concentration of CAPE as low as 1 microgram/ml, and complete inhibition of ODC induction by EGF occurred at 5 micrograms/ml. Northern analysis showed that treatment of cells with CAPE for 24 h suppressed EGF induction of ODC gene expression. Incubation of Z114 cells with CAPE for 24 h resulted in a concentration-dependent decrease in EGF binding and a 30% reduction in the EGF induced autophosphorylation of the EGF receptor. CAPE decreased both membranous and cytosolic PKC activity in a concentration- and time-dependent manner. Because significant inhibition of keratinocyte proliferation occurred at concentrations of CAPE that interfered with PKC activity and EGF signal transduction but did not cause overt toxicity, CAPE may prove useful for the treatment of hyperproliferative skin diseases.

Photoprotective effect of black tea extracts against UVB-induced phototoxicity in skin.

In previous studies, we showed that green tea and black tea extracts and their major polyphenolic constituents protect against UVB light-induced carcinogenesis in murine skin. All of these studies required chronic administration of tea extracts or specific constituents either topically or orally. However, it is not known whether acute or subchronic administration of black tea extracts or constituents can ameliorate UVB-induced early effects in skin. In the present study, cultured keratinocytes and mouse and human skin were employed to assess the effect of both oral and topical administration of standardized black tea extract (SBTE) and its two major polyphenolic subfractions namely BTF1 and BTF2 against UVB-induced photodamage. In SKH-1 hairless mice, topical application of SBTE (0.2 mg/cm2) prior to UVB exposure (180 mJ/cm2) resulted in 40% reduced incidence and 64% reduced severity of erythema and 50% reduction in skinfold thickness by day 6 when compared to nontreated UVB-exposed animals. The SBTE was also effective in protecting against UVB-induced erythema in human volunteers. Administration of SBTE 5 min after UVB irradiation was similarly effective in reducing UVB-induced inflammation in both murine and human skin. The major polyphenolic subfractions, BTF1 and BTF2, were also effective in protecting in mouse skin. The SBTE subfractions inhibited UVB-induced tyrosine phosphorylation of epidermal growth factor receptor (EGFR). The UVB irradiation of human epidermoid carcinoma cells resulted in 3.3-fold induction of tyrosine phosphorylation of EGFR. Pretreatment with BTF1 and BTF2 reduced tyrosine phosphorylation of EGFR by 53% and 31%, respectively. The UVB-mediated enhanced expression of the early response genes, c-fos and c-jun in human epidermal keratinocytes was reduced in a dose-dependent manner by SBTE. Topical application of SBTE was also effective in reducing accumulation of c-fos and p53 proteins by 82% and 78%, respectively, in UVB-exposed mouse skin. These data provide evidence that constituents of black tea can abrogate UVB-induced erythema and associated early events in murine and human skin.

Enhanced external counterpulsation as an adjunct to revascularization in unstable angina.

Enhanced external counterpulsation (EECP) is an effective noninvasive treatment for chronic stable angina. Despite intensive risk factor modification, a patient required two surgical coronary revascularizations and seven multivessel angioplasties over a 26-month period, demonstrating recurrent unstable angina and persistent thallium perfusion defects despite revascularization. Post EECP, angina was relieved, thallium defects were resolved and the patient has remained asymptomatic for 36 months.

A simple method to predict whether topical agents will interfere with phototherapy.

The objective of this study was to assess the potential interference of topical agents commonly used in psoriasis with concurrent phototherapy. Twenty-one commercially available topical agents were tested. To create solutions from the creams, lotions, and ointments, extractions were made using three different solvents (95 percent ethanol, hexanes, and 1,4-dioxane) and their absorbance from 260 to 400 nm was measured. The absorbance value of the solutions at 310 nm was used to rank the various agents in terms of potential interference with ultraviolet B (UVB) phototherapy. The absorbance at 360 nm was used to rank the agents for potential interference with psoralen/ultraviolet A (PUVA) therapy. Salicylic acid-containing preparations had substantial absorption in the UVB (280 to 320 nm) range. The tar-based products had impressive absorbance in both the UVA (320 to 400 nm) and UVB ranges. Calcipotriene (Dovonex) showed a maximal absorbance in the ultraviolet C (UVC; 200 to 280 nm) and UVB range. Tretinoin (Retin-A) had substantial absorbance in the UVA range. Anthralin (Drithocreme) revealed maximal absorbance within the UVC and UVB ranges. Topical steroid preparations and ammonium lactate (Lac-Hydrin) had low absorbance in both UVB and UVA ranges. In conclusion, salicylic acid-containing preparations, tar-based products, calcipotriene, anthralin, and most tretinoin preparations should be removed before and/or applied after phototherapy.

UVB radiation induces phosphorylation of the epidermal growth factor receptor, decreases EGF binding and blocks EGF induction of ornithine decarboxylase gene expression in SV40-transformed human keratinocytes.

We previously demonstrated that epidermal growth factor (EGF) induces a several-fold increase in ornithine decarboxylase (ODC) activity and the steady-state level of ODC mRNA in cultured SV40-transformed human keratinocytes (1). Pretreatment of cell cultures with ultraviolet B (UVB) radiation resulted in a reduction of EGF-induced ODC activity. To determine whether UVB inhibits the accumulation of ODC mRNA by EGF, cells were pretreated with 20 mJ/cm2 UVB or sham-irradiated and then incubated with 100 ng/ml EGF. Northern blot analysis revealed that UVB irradiation entirely blocked the EGF induction of ODC mRNA. Since the binding of EGF to its plasma membrane receptor is the first step in initiating a biological response, the effect of UVB on EGF binding was evaluated. UVB treatment of cultured keratinocytes resulted in an immediate and dose-dependent reduction of EGF binding. Scatchard analysis revealed that the reduction of EGF binding was due to a 52% decrease in the number of available receptors, from 6.2 x 10(4)/cell to 3.0 x 10(4)/cell. However, UVB decreased the EGF-binding affinity very little (Kd = 0.60 nM in control and Kd = 0.75 nM in UVB-treated Z114 cells). In addition, UVB did not alter the rate of EGF internalization. These data suggest that UVB blocks the signal transduction pathway of EGF that is involved in regulation of ODC gene expression. Immunoblot analysis of extracts from irradiated cells showed that UVB induced tyrosine phosphorylation of EGFR and that the quantity of EGFR protein was unaffected by UVB treatment. Phosphorylation of EGFR may be responsible for decreased binding of EGF to its receptor.

Epidermal growth factor induces ornithine decarboxylase in SV40-immortalized human keratinocytes.

The effect of epidermal growth factor (EGF) on the activity of ornithine decarboxylase (ODC) was evaluated and partially characterized in SV40-transformed, immortalized cultured human keratinocytes. It was observed that the addition of fresh complete medium to confluent cultures resulted in a 10-fold increase in ODC activity. Characterization of this activity using serum-free medium revealed that the increase in ODC activity was primarily due to the presence of EGF (10 ng/ml). A dose-dependent increase in ODC activity was observed when cultures were treated with EGF. Although near maximal induction occurred with EGF concentrations as low as 2.5-10 ng/ml, maximal induction of ODC (25-fold) occurred with an EGF concentration of 50 ng/ml. The peak time for ODC induction was 10 hours following the addition of EGF to keratinocyte cultures. The induction of ODC by EGF was inhibited by pretreatment of cultures with either cycloheximide or actinomycin D, suggesting that both protein synthesis and gene transcription are important in the EGF induction of ODC. EGF significantly increased the steady state levels of ODC mRNA with a peak at 4 hours, preceding the peak in observed enzyme activity as expected. Pretreatment of cultures with retinoic acid (10(-5)-10(-7) M) significantly inhibited the induction of ODC by EGF. Retinoic acid decreased the steady-state levels of ODC mRNA. These data demonstrate that ODC is an enzyme that is induced by EGF in human keratinocytes; this induction probably involves both gene transcription and protein synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)