Reported Signs, Symptoms, and Diagnostic Tests Before Cardiotoxicity Among Women With Breast Cancer: A Pilot Study.

BACKGROUND: Cardiotoxicity after cancer treatment is a potentially preventable life-threatening complication among women with breast cancer. There is no algorithm to identify women with breast cancer at risk of cardiotoxicity. OBJECTIVES: We quantified signs and symptoms as well as selected laboratory values among women with breast cancer who developed cardiotoxicity. METHODS: The clinical characteristics (n = 15) were collected from electronic health records. Spearman correlation coefficients and a nonparametric statistical test were used to analyze data. RESULTS: Significant statistical differences were detected in the laboratory values comparing the first and second half of 6 months before cardiotoxicity including alanine aminotransferase (U/L) (30.67 ± 26.27 and 42.31 ± 35.65, respectively; P = .03, Cohen's d = 0.37). A negative correlation was found between estimated glomerular filtration rate and new onset of more than 1 sign or symptom (Spearman's ρ = -0.5, P = .06). CONCLUSIONS: Investigating clinical characteristics before cardiotoxicity may determine the mechanism(s) and identify high-risk patients.

Association of fine-particulate and acidic-gas air pollution with premenstrual syndrome risk.

OBJECTIVE: Air pollution had been reported to be associated with the reproductive health of women. However, the association of particulate matter (PM) and acid gases air pollution with premenstrual syndrome (PMS) warrants investigation. This study investigated the effects of air pollution on PMS risk. POPULATION: We combined data from the Taiwan Air Quality-Monitoring Database and the Longitudinal Health Insurance Database. In total, an observational cohort of 85 078 Taiwanese women not diagnosed as having PMS. METHODS: Air pollutant concentrations were grouped into four levels based on the concentration quartiles of several types of air pollutants. MAIN OUTCOME MEASURES: We then applied univariable and multivariable Cox proportional hazard regression models to assess PMS risk in association with each pollutant type. RESULTS: Women exposed to Q4-level SO2 exhibited a 7.77 times higher PMS risk compared with those to Q1-level SO2 (95% confidence interval [CI] = 6.22-9.71). Women exposed to Q4-level NOx exhibited a 2.86 times higher PMS risk compared with those exposed to Q1-level NOx (95% CI = 2.39-3.43). Women exposed to Q4-level NO exhibited a 3.17 times higher PMS risk compared with women exposed to Q1-level NO (95% CI = 2.68-3.75). Finally, women exposed to Q4-level PM with a ≤2.5-µm diameter (PM2.5) exhibited a 3.41 times higher PMS risk compared with those exposed to Q1-level PM2.5 (95% CI = 2.88-4.04). CONCLUSIONS: High incidences of PMS were noted in women who lived in areas with higher concentrations of SO2, NOx, NO, NO2 and PM2.5.

Polypharmacy prior to in-hospital cardiac arrest among patients with cardiopulmonary diseases: A pilot study.

BACKGROUND: Patterns of medication administration prior to in-hospital cardiac arrest (I-HCA) and the potential impact of these on patient outcomes is not well-established. Accordingly, types of medications administered in the 72 h prior to I-HCA were examined in relation to initial rhythms of I-HCA and survival. METHODS: A retrospective, pilot study was conducted among 96 patients who experienced I-HCA. Clinical characteristics and treatments including medications were extracted from electronic health records. Relative risk (RR) of medications or class of medications associated with the initial rhythms of I-HCA and return of spontaneous circulation (ROSC) were calculated. RESULTS: Two distinct sub-groups were identified that did not survive to hospital discharge (n = 31): 1) those who received either vasopressin/desmopressin (n = 16) and 2) those who received combinations of psychotherapeutic agents with anxiolytics, sedatives, and hypnotics (n = 15) prior to I-HCA. The risk of pulseless electrical activity and asystolic arrest was high in patients who received sympathomimetic agents alone or in combination with ß-Adrenergic blocking agents, (RR = 1.40, 1.41, respectively). Vasopressin and a combination of vasopressin and fentanyl were associated with risk of unsuccessful ROSC (RR = 2.50, 2.38, respectively). CONCLUSIONS: The types of medications administered during inpatient care may serve as a surrogate marker for identifying patients at risk of specific initial rhythms of I-HCA and survival.

Optimal generation of spatially coherent soft X-ray isolated attosecond pulses in a gas-filled waveguide using two-color synthesized laser pulses.

We numerically demonstrate the generation of intense, low-divergence soft X-ray isolated attosecond pulses in a gas-filled hollow waveguide using synthesized few-cycle two-color laser waveforms. The waveform is a superposition of a fundamental and its second harmonic optimized such that highest harmonic yields are emitted from each atom. We then optimize the gas pressure and the length and radius of the waveguide such that bright coherent high-order harmonics with angular divergence smaller than 1 mrad are generated, for photon energy from the extreme ultraviolet to soft X-rays. By selecting a proper spectral range enhanced isolated attosecond pulses are generated. We study how dynamic phase matching caused by the interplay among waveguide mode, neutral atomic dispersion, and plasma effect is achieved at the optimal macroscopic conditions, by performing time-frequency analysis and by analyzing the evolution of the driving laser's electric field during the propagation. Our results, when combined with the on-going push of high-repetition-rate lasers (sub- to few MHz's) may eventually lead to the generation of high-flux, low-divergence soft X-ray tabletop isolated attosecond pulses for applications.

Extracting conformational structure information of benzene molecules via laser-induced electron diffraction.

We have measured the angular distributions of high energy photoelectrons of benzene molecules generated by intense infrared femtosecond laser pulses. These electrons arise from the elastic collisions between the benzene ions with the previously tunnel-ionized electrons that have been driven back by the laser field. Theory shows that laser-free elastic differential cross sections (DCSs) can be extracted from these photoelectrons, and the DCS can be used to retrieve the bond lengths of gas-phase molecules similar to the conventional electron diffraction method. From our experimental results, we have obtained the C-C and C-H bond lengths of benzene with a spatial resolution of about 10 pm. Our results demonstrate that laser induced electron diffraction (LIED) experiments can be carried out with the present-day ultrafast intense lasers already. Looking ahead, with aligned or oriented molecules, more complete spatial information of the molecule can be obtained from LIED, and applying LIED to probe photo-excited molecules, a "molecular movie" of the dynamic system may be created with sub-Ångström spatial and few-ten femtosecond temporal resolutions.

Thyroid hormone receptor represses miR-17 expression to enhance tumor metastasis in human hepatoma cells.

MicroRNAs (miRNAs) are thought to control tumor metastasis through direct interactions with target genes. Thyroid hormone (T3) and its receptor (TR) are involved in cell growth and cancer progression. However, the issue of whether miRNAs participate in T3/TR-mediated tumor migration is yet to be established. In the current study, we demonstrated that T3/TR negatively regulates mature miR-17 transcript expression, both in vitro and in vivo. Luciferase reporter and chromatin immunoprecipitation (ChIP) assays localized the regions responding to TR-mediated repression to positions -2234/-2000 of the miR-17 promoter sequence. Overexpression of miR-17 markedly inhibited cell migration and invasion in vitro and in vivo, mediated via suppression of matrix metalloproteinases (MMP)-3. Moreover, p-AKT expression was increased in miR-17-knockdown cells that led to enhanced cell invasion, which was blocked by LY294002. Notably, low miR-17 expression was evident in highly metastatic cells. The cell migration ability was increased by T3, but partially reduced upon miR-17 overexpression. Notably, TRα1 was frequently upregulated in hepatocellular carcinoma (HCC) samples and associated with low overall survival (P=0.023). miR-17 expression was significantly negatively associated with TRα1 (P=0.033) and MMP3 (P=0.043) in HCC specimens. Data from our study suggest that T3/TR, miR-17, p-AKT and MMP3 activities are interlinked in the regulation of cancer cell metastasis.

Gustatory changes in patients with chronic otitis media, before and after middle-ear surgery.

OBJECTIVE: We investigated gustatory changes in patients with chronic otitis media, before and after middle-ear surgery. METHODS: This prospective study included 38 patients with unilateral chronic otitis media. We used taste testing solutions to evaluate each patient's taste function. Intra-operative assessments of the chorda tympani nerve were also compared and analysed. RESULTS: Patients with chronic otitis media had significantly worse ipsilateral perception of sour, bitter and salty tastes. In patients with good intra-operative preservation of the chorda tympani nerve, there was significant improvement in gustatory function one month post-operatively, compared with the pre-operative baseline. In patients who sustained intra-operative chorda tympani nerve injury, one month post-operative gustatory function was the same as the pre-operative baseline. CONCLUSION: Middle-ear surgery for chronic otitis media not only treats the ear but also improves gustatory function in the majority of patients. In patients with intra-operative injury to the chorda tympani nerve, post-operative taste decline is only temporary.

Laser-induced electron diffraction for probing rare gas atoms.

Recently, using midinfrared laser-induced electron diffraction (LIED), snapshots of a vibrating diatomic molecule on a femtosecond time scale have been captured [C.I. Blaga et al., Nature (London) 483, 194 (2012)]. In this Letter, a comprehensive treatment for the atomic LIED response is reported, a critical step in generalizing this imaging method. Electron-ion differential cross sections (DCSs) of rare gas atoms are extracted from measured angular-resolved, high-energy electron momentum distributions generated by intense midinfrared lasers. Following strong-field ionization, the high-energy electrons result from elastic rescattering of a field-driven wave packet with the parent ion. For recollision energies ≥100 eV, the measured DCSs are indistinguishable for the neutral atoms and ions, illustrating the close collision nature of this interaction. The extracted DCSs are found to be independent of laser parameters, in agreement with theory. This study establishes the key ingredients for applying LIED to femtosecond molecular imaging.

Three-dimensional image analysis of the temporal bone in patients with unilateral attic cholesteatoma.

We determined temporal bone anatomy in patients with unilateral attic cholesteatoma. We compared the affected and normal ears of ten patients with unilateral attic cholesteatoma using three-dimensionally reconstructed high-resolution computed tomography images of the temporal bone. We determined the eustachian tube angle, eustachian tube length, sizes of the tympanic orifice of the eustachian tube, the pars flaccida, and the mastoid cavity, and distances of the pars flaccida and the tympanic orifice of the eustachian tube from the epitympanic roof. No significant differences were found between the normal and affected ears with regard to the size of the eustachian tube orifice, eustachian tube length or distances of the pars flaccida and the tympanic orifice of the eustachian tube from the epitympanic roof. By contrast, the mastoid cavity and the eustachian tube angle were significantly larger in the normal ears than in the affected ears [mean, 6.99 cm(3) (S.D.,4.9 cm(3)) vs. 1.28 cm(3) (0.81 cm(3)) and 16.7° (4.12°) vs. 13.89° (5.30°), respectively]. The pars flaccida was significantly smaller in the normal ears [1.07 cm (0.31 cm)] than in the affected ears [2.19 cm (0.77 cm)]. The inherent anatomy of the eustachian tube may be particularly important in the formation of attic cholesteatomas.

Oxidative stress in nonallergic nasal polyps associated with bronchial hyperresponsiveness.

BACKGROUND: Nasal polyposis (NP) is a chronic inflammatory disease of upper airway with unknown etiology. NP is frequently associated with asthma; the interaction between these comorbidities remains interesting. Oxidative stress has been implicated in the pathophysiology of NP and asthma. The aim of this study is to investigate the significance of oxidative stress in sinonasal microenvironments by evaluating its association with clinopathological parameters and its impacts on the pathogenesis of bronchial hyperresponsiveness (BHR) in NP. METHODS: Polyp biopsy specimens were obtained from 20 nonallergic patients; control mucosas were obtained from 20 volunteers. The levels of free radicals in the tissues and in blood were determined by a sensitive chemiluminescence (CL) method. NP patients were substratified into three subgroups, NP without BHR, NP with asymptomatic BHR, and NP with BHR and asthma by the results of provocative testing. Four histological characteristics of NP, inflammatory cells, eosinophil infiltration, edema and fibrosis were estimated and applied to correlate with the tissue-CL. RESULTS: The mean CL level in polyp-tissues, but not in blood, was higher than in the control specimens. In NP patients, tissue-CL was associated with endoscopy score; high tissue-CL levels were positively correlated with the abundance of inflammatory cells and eosinophils. Tissue-CL and endoscopy score were associated with BHR/asthma phenotype. CONCLUSION: These results suggest an important role for oxidative stress in the pathophysiology of NP and a causal relation between oxidative stress and inflammatory cells, especially the eosinophils. Free radical levels in polyp-tissues associated with NP severity and with BHR/asthma phenotype in nonallergic NP patients.

Preoperative diagnosis by electron beam computed tomography and perioperative management of primary tracheal anomalies in tetralogy of Fallot.

PURPOSE: To investigate the usefulness of electron beam computed tomography (EBCT) in the preoperative detection and perioperative management of insidious concomitant primary tracheobronchial anomalies in patients with tetralogy of Fallot (TF). METHODS: From July 1995 to October 1999, 88 children (38 girls, 50 boys) with TF were enrolled in this study. EBCT examinations provided information needed to plan management. The final diagnoses of airway abnormalities were correlated with the findings of bronchoscopy in five patients and confirmed during surgery. RESULTS: Fourteen (16%) of the 88 patients had associated primary tracheobronchial anomalies. Nine patients had tracheal bronchi, which were combined with tracheobronchial stenosis in two patients and with tracheal stenosis in one patient. Two patients had tracheal diverticulum, which was combined with lower tracheal stenosis in one patient. Two patients had congenital tracheal stenosis. Tracheomalasia was found in one patient. Three patients with ventilation difficulties died postoperatively. Special attention was given to the care of the diseased airways perioperatively, and the remaining 11 patients had a smooth course of hospitalization and discharge. CONCLUSIONS: Our results show that EBCT provides good delineation of both cardiac and tracheobronchial anomalies and suggest that it should be used perioperatively to detect associated airway anomalies in TF, to facilitate the design of an appropriate ventilation care strategy.

Clinical experiences of removing foreign bodies in the airway and esophagus with a rigid endoscope: a series of 3217 cases from 1970 to 1996.

This study examined 11,333 rigid endoscopy procedures performed in the Department of Otolaryngology, National Taiwan University Hospital, during a 27-year period from 1970 to 1996. Among these cases, 3217 were performed to remove foreign bodies from the airway (459 cases, 14.3%) and esophagus (2758 cases, 85.7%). Retrospective analysis of these data revealed that peanuts (217 cases) and animal bones (1184 cases) were the most frequent foreign bodies encountered in the airway and esophagus, respectively. The successful rate of removal of these foreign bodies was 99.9% (3213/3217). The complication rate was only 0.2% (8/3217), and the mortality rate was less than 0.1% (2/3217). On the basis of these results, we conclude that foreign bodies in the airway and esophagus can be removed safely under direct visualization through rigid endoscopy with relatively few complications. A significant finding in this study is the declining trend in the number of cases in recent years. Despite the decline in the number of procedures, endoscopic removal of foreign bodies remains as a vital skill of the aerodigestive tract surgeon.

Clinical experience in airway endoscopy in children: an emphasis on the comparison between flexible and rigid endoscopy.

Congenital and acquired lesions of the pediatric airway frequently pose perplexing problems in children, infants and newborns. Prompt investigation into the etiology and early intervention are essential to decrease the morbidity and to prevent some tragic events. Endoscopy grants access to the lesion sites for either diagnostic or therapeutic purposes. From April 1994 to May 1997, totally 509 endoscopic procedures, including 292 flexible and 217 rigid endoscopic procedures were performed in 296 pediatric patients at National Taiwan University Hospital. For routine diagnostic procedures, the flexible fiberscope is the instrument of choice which should include a detailed examination of entire upper airway, as farther to tracheobronchi as possible. When flexible endoscopy fails to demonstrate the exact airway lesion or certain surgical manipulation is demanded, rigid endoscopy is favored. The indications for endoscopy were: stridor, respiratory distress, follow-up endoscopy or tracheostoma evaluation, feeding difficulty, hoarseness or weak voice, and suspicious airway foreign body. Common airway problems in serial orders were: laryngomalacia, subglottic stenosis, tracheo/bronchomalacia and airway foreign body. Nearly 20% of patients in this series had multiple synchronous airway lesions. There was no major complication in our 292 flexible endoscopic procedures. Two major complications attributed to endoscopic manipulations occurred in 217 rigid endoscopic procedures.

[Relationship between thyroid echogram and thyroid function in Hashimoto's thyroiditis].

Seventeen cases of untreated Hashimoto's thyroiditis were selected from the files of the Taipei Municipal Jen-Ai Hospital during the period from Jan. 1985 to Jan. 1986. All the cases were confirmed by a physical examination, determination of thyroid antibodies and fine needle aspiration cytology. Thyroid function was also determined. According to the echogenicity of the thyroid, they were divided into 2 groups, group A (8 cases) and group B (9 cases). In group A, homogeneous hypoechogenicity of the thyroid was noted and was lower than that of the adjacent muscles. In group B, heterogeneous echogenicity of the thyroid with equal or higher echogenicity than that of the adjacent muscles was noted. Group A showed a significantly lower serum T4, T3 and a higher serum TSH in comparison with group B. Five cases in group A presented hypothyroidism clinically while only 1 in group B presented. In conclusion, in the cases of Hashimoto's thyroiditis, the homogeneous hypoechogenicity of the thyroid echogram suggested the possibility of hypothyroidism. Statistically, the sensitivity was 83.3%, specificity 72.8%, positive prediction value 62.5% and the negative prediction value was 88.9%.

Gastric xanthelasma.

Gastric xanthelasmas are macroscopically well demarcated yellow or yellow-white plaques, and microscopically composed of typical foamy macrophages. Of 3870 patients who underwent upper gastrointestinal panendoscopic examinations, 30 (0.8%) were found to have gastric xanthelasma. A moderate predominance of males over females (M:F = 3.3:1) was noted. The age ranged between 21 and 69 years (mean 46.7). Frequency peaked in those from 40 to 60 years of age (53.3%). Single lesions were found in 26 patients and multiple in 4, with diameters of 1-6 mm, nearly 66.7% of which were 2-3 mm. Gastric xanthelasmas are most frequently found in the antrum (67.8%), especially along the lesser curvature. Associated chronic gastritis in the xanthelasma surrounding mucosa was found in the 30 patients and intestinal metaplasia in 4 (13.3%). The cause of gastric xanthelasma is unknown, but chronic gastritis may be the most plausible etiologic factor.

Monoclonal antibodies to a benzo[a]pyrene diolepoxide modified protein.

Monoclonal antibodies have been developed which specifically recognize protein modified by 7 beta,8 alpha-dihydroxy-9 alpha,10 alpha-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE-I). These antibodies have been characterized as to sensitivity and specificity by an enzyme-linked immunosorbent assay. They react with BPDE-I-modified proteins and do not cross-react with non-modified protein. All the antibodies have higher sensitivity toward BPDE-I-tetraols than to BPDE-I-modified protein. They cross-react with BPDE-I-deoxyguanosine, BPDE-I-DNA and BPDE-II-rabbit serum albumin. Because of the high antibody sensitivity for tetraols, an immunoassay was developed for quantitating DNA and protein adducts based on release of tetraols from modified samples. This approach was validated using radiolabeled BPDE-I modified DNA and protein.

Quantitation of exposure to benzo[a]pyrene with monoclonal antibodies.

It is now possible to quantitate carcinogen adducts on DNA by highly sensitive immunoassays. These techniques are particularly useful for screening human populations for exposure to potential environmental carcinogens. We have developed a panel of monoclonal antibodies that react with benzo(a)pyrene (BP) modified DNA to be used in an enzyme linked immunoassay (ELISA) to quantitate adduct levels of both human and animal samples. BALBc/Cr mice were immunized with either DNA modified by 7 beta, 8 alpha-dihydroxy-9 alpha, 10 alpha-epoxy-7,8,9, 10-tetrahydrobenzo(a)pyrene (BPDE-I-DNA) complexed electrostatically to methylated bovine serum albumin or with BPDE-I-modified guanosine conjugated with bovine serum albumin (BPDE-I-G-BSA). Four stable clones were produced from the spleen cells of animals immunized with BPDE-I-DNA and one from BPDE-I-G-BSA immunized animals. All antibodies were shown to be highly specific for BPDE-I-DNA and did not crossreact with nonmodified DNA or with N-2-acetylaminofluorene or 1-aminopyrene modified DNA. The antibodies differed in their sensitivity to BPDE-II-DNA, BPDE-I-poly G, BPDE-I-tetraols and BPDE-I-dG. In general, all the antibodies showed the greatest affinity for their original antigen. Those generated against modified DNA showed highest reactivity against modified DNA while the one antibody generated against the monoadduct showed highest reactivity with the monoadduct. These antibodies are currently being used in a highly sensitive competitive ELISA to quantitate levels of BP-DNA adducts in various animal and human tissue samples.

Monoclonal antibodies to DNA modified by a benzo[a]pyrene diol epoxide.

Monoclonal antibodies were obtained after fusion of mouse P3 X 63 Ag8.653 myeloma cells with spleen cells isolated from BALB/cCr mice immunized with either DNA modified by 7 beta, 8 alpha-dihydroxy-9 alpha,10 alpha-epoxy-7,8,9,10-tetrahydrobenzo[a]-pyrene (BPDE-I-DNA) complexed electrostatically to methylated bovine serum albumin or with BPDE-I modified guanosine conjugated with bovine serum albumin, BPDE-I-G-BSA. One monoclonal hybridoma line from each type of immunization was grown as ascites tumors or in defined media and characterized in an enzyme linked immunosorbent assay (ELISA). The antibody produced from the spleen cells of a BPDE-I-DNA immunized mouse, designated 5D11, recognizes BPDE-I-DNA and DNA modified by 7 beta,8 alpha-dihydroxy-9 beta,10 beta-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE II) but not unmodified DNA, N-2-acetylaminofluorene (AAF) or 1-nitropyrene (NP) modified DNA, BPDE-II-dG or BPDE-I tetraol. It does recognize BPDE-I-dG but with a much lower affinity than when the adduct is present in DNA. In contrast, antibody 8E11 produced from the spleen cells of a BPDE-I-G-BSA immunized mouse recognizes the monoadduct BPDE-I-dG better than BPDE-I-DNA. It also recognizes BPDE-I tetraol but not BPDE-II-DNA, unmodified DNA, AAF- or NP-DNA or BPDE-II-dG. In a noncompetitive ELISA as little as 3 fmol of BPDE-I-DNA adduct can be detected with either antibody 5D11 or 8E11. The combination of the highly sensitive ELISA and highly specific monoclonal antibodies should be valuable in the detection and quantitation of human exposure to benzo[a]pyrene.