Real-time heart rate variability according to ambulatory glucose profile in patients with diabetes mellitus.

Background: Autonomic neuropathy commonly occurs as a long-term complication of diabetes mellitus (DM) and can be diagnosed based on heart rate variability (HRV), calculated from electrocardiogram (ECG) recordings. There are limited data on HRV using real-time ECG and ambulatory glucose monitoring in patients with DM. The aim of this study was to investigate real-time HRV according to ambulatory glucose levels in patients with DM. Methods: A total of 43 patients (66.3 ± 7.5 years) with DM underwent continuous real-time ECG monitoring (225.7 ± 107.3 h) for HRV and ambulatory glucose monitoring using a remote monitoring system. We compared the HRV according to the ambulatory glucose profile. Data were analyzed according to the target in glucose range (TIR). Results: There were no significant differences in the baseline characteristics of the patients according to the TIR. During monitoring, we checked ECG and ambulatory glucose levels (a total of 15,090 times) simultaneously for all patients. Both time- and frequency-domain HRVs were lower when the patients had poorly controlled glucose levels (TIR < 70%) compared with well controlled glucose levels (TIR > 70%). In addition, heart and respiratory rates increased with real-time glucose levels (P < 0.001). Conclusions: Poorly controlled glucose levels were independently associated with lower HRV in patients with DM. This was further substantiated by the independent continuous association between real-time measurements of hyperglycemia and lower HRV. These data strongly suggest that cardiac autonomic dysfunction is caused by elevated blood sugar levels.

Transrenal DNA detection of Mycobacterium tuberculosis in patients with pulmonary tuberculosis.

Background: Multiple attempts have been made to use biological samples other than sputum to diagnose tuberculosis (TB). Sputum acid-fast bacillus (AFB) microscopy is the fastest, most straightforward, and most inexpensive method for diagnosing pulmonary TB. However, urine can be used in place of sputum owing to its various advantages, such as a noninvasive method of collection, convenient handling and storage, and minimal risk of infection in health-care workers involved in sample collection. In this study, we aimed to assess the suitability of urine as a sample to obtain transrenal DNA (trDNA) to diagnose TB. This study involved several patients with TB undergoing inpatient treatment, whose AFB microscopy showed negative inversion. Methods: Here, 51 urine samples were collected from 40 patients with TB and examined to confirm the presence of trDNA. First, we compared the efficiency of two trDNA extraction methods.An automated magnetic bead-based method and a more efficient anchoring extraction method. Statistical analyses were performed using Excel software (Microsoft Office Professional Plus 2019). Results: Although molecular diagnosis using GeneXpert yielded negative results, a peculiarity was observed. There was no significant difference between GeneXpert findings and our results nor was there any difference in the sequential trDNA samples obtained. However, even when GeneXpert results were negative, trDNA was detected in seven out of ten samples using the anchor extraction method. Conclusions: Further studies are needed to establish biomarkers for the progression of TB treatment.

High Serum Folate Concentration Is Associated with Better Lung Function in Male Chronic Obstructive Pulmonary Disease Patients Who Are Current Smokers: Analysis of Nationwide Population-Based Survey.

Folate, folic acid, has a role in mitigating inflammatory reactions in the human body. This study aimed to evaluate the association of serum folate levels with lung function in chronic obstructive pulmonary disease (COPD) patients. Of the 8149 participants of the 2016 Korean National Health and Nutrition Examination Survey (KNHANES), 311 subjects (192 males and 119 females) having COPD defined by the lower fifth percentile of the reference population were selected. Pearson's correlation coefficient was used to investigate the relationship between serum folate level and lung function measurements. The association between the serum folate level and lung function in patients with COPD was evaluated using multivariable linear regression analysis after adjustment for age, sex, height, high sensitivity C-reactive protein, total calorie intake, residence, smoking status and smoking pack-years, education, and household income. The serum folate level showed a positive correlation with the predicted percentage of forced expiratory volume in one second (FEV1%). In males, a trend for a positive correlation with serum folate level was observed in predicted FEV1%, FEV1 value, predicted percentage of forced vital capacity (FVC%), FVC value, and peak expiratory flow (PEF). No significant correlation between the serum folate level and lung function in females was observed. In the multivariable linear regression model, the serum folate level was associated with an increase in predicted FEV1%, FEV1 value, predicted FVC%, FVC value, and PEF; however, the significance was only observed in males, especially among current smokers. High serum folate level was positively associated with lung function measurements in male COPD patients who were current smokers. Further longitudinal studies are needed to elucidate the underlying mechanisms.

Tracheal pleomorphic adenoma with coexisting pulmonary tuberculoma.

Tracheal tumors are rare and difficult to diagnose. Moreover, delays in diagnosis are very common because the symptoms are nonspecific. As a result, tracheal tumors are commonly mistreated as chronic obstructive pulmonary disease or bronchial asthma. We report a case of a 49-year-old male who presented with a 3-month history of dyspnea and cough. Chest computed tomography scan showed a 1.5×1.3 cm homogenous tumor originating from the right lateral wall of the tracheobronchial angle into the tracheal lumen as well as a 0.5×0.4 cm round nodular lesion at the right upper lobe with multiple mediastinal lymph nodes enlargement. Bronchoscopic findings revealed a broad-based, polypoid lesion nearly obstructing the airway of the right main bronchus. The patient was diagnosed with pleomorphic adenoma which is the most common benign tumor of the salivary glands, but rarely appears in the trachea. Upon surgery, tracheal pleomorphic adenoma and co-existing active pulmonary tuberculoma that had been mistreated as bronchial asthma over 3 months was revealed. Following surgery, the patient underwent anti-tuberculosis treatment. No recurrence has been detected in the 3 years since treatment and the patient is now asymptomatic.

Neuron-specific enolase as a novel biomarker reflecting tuberculosis activity and treatment response.

BACKGROUND/AIMS: It is not clear which tests are indicative of the activity and severity of tuberculosis (TB). This study aimed to investigate the predictive value of neuron-specific enolase (NSE) and to determine the origin of NSE in TB patients. METHODS: A single-center retrospective analysis was conducted on newly diagnosed TB patients between January and December 2010. Patients were categorized into one of two disease groups (focal segmental or extensive) based on chest X-ray. Pre- and post-treatment NSE concentrations were evaluated. To determine the origin of serum NSE concentration, NSE staining was compared with macrophage-specific CD68 staining in lung tissues and with a tissue microarray using immunohistochemistry and immunofluorescence. RESULTS: A total of 60 newly diagnosed TB patients were analyzed. In TB patients, NSE serum concentration was significantly increased and NSE level decreased after treatment (p < 0.001). In proportion to serum high-sensitivity C-reactive protein concentration, the mean serum concentration of NSE in the extensive group (25.12 ng/mL) was significantly higher than that in the focal segmental group (20.23 ng/mL, p = 0.04). Immunohistochemical staining revealed a large number of macrophages that stained positively for both NSE and CD68 in TB tissues. In addition, NSE signals mostly co-localized with CD68 signals in the tissue microarray of TB patients. CONCLUSIONS: Our results suggest that NSE may be a practical parameter that can be used to monitor TB activity and treatment response. Elevated serum NSE level originates, at least in part, from macrophages in granulomatous lesions.

The potential application of photodynamic therapy in drug-resistant tuberculosis.

Tuberculosis (TB) is an infectious bacterial disease that has historically created a high global health burden. Unfortunately, the emergence of drug-resistant TB (DR-TB), which includes multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB), has greatly affected the treatment of TB. Anti-TB chemotherapy drugs are classified into five groups to facilitate application of effective guidelines for the treatment regimen. However, chemotherapy has a limited ability to treat DR-TB, and therefore a novel alternative treatment for DR-TB is required. In this review, we focused on photodynamic therapy (PDT) as potential treatment for DR-TB. PDT is a widely used cancer treatment that combines photosensitizers and harmless laser light to produce reactive oxygen species that selectively damage the target cells. Initially, PDT was originally developed to target pathogenic microorganisms but fell into disuse because of adverse reactions. Recently, photodynamic antimicrobial chemotherapy is attracting attention again as an alternative treatment for bacterial infections. In our previous study, we suggested that PDT could be a novel option to treat MDR- and XDR-TB in vitro. Despite the limited previous studies regarding PDT in TB models, fast-developing bronchoscopic technologies and clinician experience will soon facilitate the clinical application of safe and minimally invasive PDT for TB.

Current iodine nutrition status and awareness of iodine deficiency in tuguegarao, Philippines.

The Philippines is one of the countries where adequate iodine status has been achieved. However, iodine deficiency still remains an important public health problem in this country. In this study, we evaluated iodine nutrition status and investigated an awareness status of iodine deficiency targeting high school students of Tuguegarao, Philippines. A total of 260 students provided samples for urinary iodine analysis, among which 146 students completed thyroid volume measurement by ultrasonography and answering the questionnaires. The median urinary iodine level was 355.3 µg/L and only 3.8% of the students were in the range of iodine deficiency status according to the ICCIDD criteria. Although 62.3% of students answered that they can list problems resulting from iodine deficiency, a majority of students (70.5%) were unable to identify problems other than goiter. They did not appreciate that adequate iodine levels are important during pregnancy and for development of children. 33.6% of students answered that they did not use iodized salt and the biggest reason was that they did not find it necessary. Based on these results, we suggest that a future strategy should be focused on vulnerable groups to completely eliminate iodine deficiency, including women at their reproductive ages and during pregnancy.

Over-expression of thymosin ß4 in granulomatous lung tissue with active pulmonary tuberculosis.

Recent studies have shown that thymosin ß4 (Tß4) stimulates angiogenesis by inducing vascular endothelial growth factor (VEGF) expression and stabilizing hypoxia inducible factor-1α (HIF-1α) protein. Pulmonary tuberculosis (TB), a type of granulomatous disease, is accompanied by intense angiogenesis and VEGF levels have been reported to be elevated in serum or tissue inflamed by pulmonary tuberculosis. We investigated the expression of Tß4 in granulomatous lung tissues at various stages of active pulmonary tuberculosis, and we also examined the expression patterns of VEGF and HIF-1α to compare their Tß4 expression patterns in patients' tissues and in the tissue microarray of TB patients. Tß4 was highly expressed in both granulomas and surrounding lymphocytes in nascent granulomatous lung tissue, but was expressed only surrounding tissues of necrotic or caseous necrotic regions. The expression pattern of HIF-1α was similar to that of Tß4. VEGF was expressed in both granulomas and blood vessels surrounding granulomas. The expression pattern of VEGF co-localized with CD31 (platelet endothelial cell adhesion molecule, PECAM-1), a blood endothelial cell marker, and partially co-localized with Tß4. However, the expression of Tß4 did not co-localize with alveolar macrophages. Stained alveolar macrophages were present surrounding regions of granuloma highly expressing Tß4. We also analyzed mRNA expression in the sputum of 10 normal and 19 pulmonary TB patients. Expression of Tß4 was significantly higher in patients with pulmonary tuberculosis than in normal controls. These data suggest that Tß4 is highly expressed in granulomatous lung tissue with active pulmonary TB and is associated with HIF-1α- and VEGF-mediated inflammation and angiogenesis. Furthermore, the expression of Tß4 in the sputum of pulmonary tuberculosis patients can be used as a potential marker for diagnosis.

Methylene blue-mediated photodynamic therapy enhances apoptosis in lung cancer cells.

Combined treatment with a photosensitizer and iodide laser [photodynamic therapy (PDT)] has improved the outcome of various cancers. In this study, we investigated the effects of using the photosensitizer methylene blue (MB) in PDT in human lung adenocarcinoma cells. We found that MB enhances PDT-induced apoptosis in association with downregulation of anti-apoptotic proteins, reduced mitochondrial membrane potential (MMP), increased phosphorylation of the mitogen-activated protein kinase (MAPK) and the generation of reactive oxygen species (ROS). In MB-PDT-treated A549 cells, we observed PARP cleavage, procaspase-3 activation, downregulation of the anti-apoptotic proteins Bcl-2 and Mcl-1, and the reduction of mitochondrial membrane potential (MMP). Western blot data showed that phosphorylation of p38 was increased in MB-PDT-treated A549 cells, indicating that several signaling molecules participate in the apoptotic cascade. Our data also showed that apoptotic cell death in MB-PDT-treated cells occurred through a series of steps beginning with the photochemical generation of ROS. Demonstrating the role of ROS, pretreatment of A549 cells with the antioxidant N-acetylcysteine (NAC) followed by MB-PDT resulted in increased cell viability and reduced proteolytic cleavage of PARP.

Successful treatment of a tracheal squamous cell carcinoma with a combination of cryoablation and photodynamic therapy.

Malignant tumors of the trachea are rare, and account for less than 0.1% of all malignancies. Because there are no guidelines based on randomized clinical trials, the choice of treatment modalities and optimal sequences have not yet been established. In most cases of malignant airway obstruction, a single modality is chosen as the treatment of choice for management, but complete ablation becomes increasingly problematic with minimal residual lesions that require additional treatment. There were few case reports of the combined use of cryoablation and photodynamic therapy to treat tracheal cancer. Therefore, we present our experience of successful tracheal cancer treatment using this combination therapy. A bronchoscopic complete regression was obtained using these two modalities, and the procedures proved to be a safe and effective treatment option based on a one-year follow-up.

Potential molecular approaches for the early diagnosis of lung cancer (review).

Lung cancer is the leading cause of mortality from cancer among men and women worldwide. More individuals die each year of lung cancer than of colon, breast and prostate cancer combined. Despite new diagnostic techniques, the overall 5-year survival rate remains at approximately 15% and the majority of patients still present with advanced disease. Therefore, lung cancer is the most lethal cancer at present. Diagnosing and treating cancer at its early stages, ideally during the precancerous stages, could increase the 5-year survival rate by 3-4­fold, with the possibility of cure. To date, no screening method has been shown to decrease the disease-specific mortality rate. This review describes issues related to early lung cancer screening and their rationale, the management of primary cancers detected by screening and the different approaches that have been tested for cancer screening; these include imaging techniques, bronchoscopies and molecular screening, such as analysis of epigenomics using different noninvasive or invasive sources, such as blood, sputum, bronchoscopic samples and exhaled breath.

Nuclear factor-kappa B is not involved in titanium dioxide-induced inflammation.

Research over recent years have shown that titanium dioxide (TiO2) nanoparticles (NPs) induce inflammation in various lung, kidney, liver and brain cells. Although the mechanism of inflammation is unclear, existing literature suggests the underlying role of oxidative stress. On the other hand, it has also been shown that nuclear factor-kappa B (NF-kappaB) is activated in response to pro-inflammatory cytokines. In this study we investigated the involvement of NF-kappaB in TiO2-induced inflammation in human lung adenocarcinomic epithelial cells (A549 cells). After 24h of treatment, IL-8 protein release from A549 cells, induced by 10, 50 and 250 microg/ml of P25 TiO2 NPs, were statistically significantly raised, compared to that of the control. This finding corroborates existing literature in that TiO2 NPs induce a dose-dependent increase in the release of IL-8 protein when exposed to A549 cells. However, the binding of NF-kappaB DNA was not affected after 6 h of incubation with P25. Therefore, NF-kappaB DNA binding is not the likely transcription pathway that leads to TiO2-induced inflammation.

Determination of thyroid volume by ultrasonography among schoolchildren in Philippines.

OBJECTIVE: Iodine deficiency is defined by the goiter and the urinary iodine concentration. However, a lack of local thyroid volume reference data resulted in the vague definition of goiter, especially in school-aged children. The aim of this paper was to determine the thyroid volumes by ultrasonography in schoolchildren aged 6 to 12 years living in Cagayan areas in Philippine. METHODS: Cross-sectional thyroid ultrasonographic data of 158 schoolchildren aged 6-12 years from Tuguegarao and Lagum in Cagayan valley, Philippine were used. Thyroid volumes were compared based on logistic issue and urban and rural area and compared with other previously reported data. RESULTS: The mean values of thyroid volume in Tuguerago and Lagum were 2.99 ± 1.34 mL and 2.42 ± 0.92 mL. The thyroid size was significantly in association with age (P < 0.00), weight (P < 0.00), height (P < 0.00), and BSA (P < 0.00) by Pearson's correlation. The median thyroid volumes of schoolchildren investigated in this study were generally low compared to international reference data by age group but not by BSA. CONCLUSIONS: We propose for the first time local reference ultrasound values for thyroid volumes in 6-12 aged schoolchildren that should be used for monitoring iodine deficiency disorders.

A case of pneumothorax treated with thoracoscopic pleurodesis.

A 75 year-old male patient presented with exertional dyspnea that he had suffered for 7 days. The chest X-ray showed right-sided pneumothorax. Closed thoracostomy was performed on the 1st day of hospitalization and repeated with talc sclerotherapy and lower-power suction, but neither could improve air-leakage. On the 14th day of hospitalization, thoracoscopy via pleurodesis was performed and the pneumothorax resolved. We report here on a rare case of intractable pneumothorax treated by thoracoscopic pleurodesis with talc.

Assessment of village health worker training program in Tuguegarao, Philippine.

OBJECTIVES: This study was performed to evaluate the effectiveness of 'village health worker training program' which aimed to build community participatory health promotion capacity of community leaders in villages of low developed country and to develop methods for further development of the program. METHODS: The intervention group were 134 community leaders from 25 barangays (village). Control group were 149 form 4 barangays. Intervention group participated 3-day training program. Questionnaire was developed based on 'Health Promotion Capacity Checklist' which assessed capacity in 4 feathers; 'knowledge', 'skill', 'commitment', and 'resource'. Each feather was assessed in 4 point rating scale. Capacity scores between intervention group and control group were examined to identify changes between the pre- and post-intervention periods. A qualitative evaluation of the program was conducted to assess the appropriateness of the program. The program was conducted in Tuguegarao city, Philippine in January, 2009. RESULTS: The result showed significant increases in the total health promotion capacity and each feather of health promotion capacities between pre and post assessment of intervention group. But there was no significant change in that of control group. Participants marked high level of satisfaction for preparedness, selection of main subjects and education method. Qualitative evaluation revealed that training program facilitated community participatory health promotion capacity of participants. CONCLUSIONS: This study suggested that the Village health worker training program is effective for building health promotion capacity of community leaders and it can be a main method for helping low developed countries with further development.

EGFR and KRAS mutations in patients with adenocarcinoma of the lung.

BACKGROUND/AIMS: Mutations of the epidermal growth factor receptor (EGFR) and Kirsten rat sarcoma viral oncogene (KRAS) are important in the pathogenesis of lung cancer, and recent reports have revealed racial and geographical differences in mutation expression. METHODS: This study was conducted to investigate the prevalence of EGFR and KRAS mutations and their correlation with clinical variables in Korean patients with adenocarcinoma of the lung. Formalin-fixed adenocarcinoma specimens from 104 randomly selected patients diagnosed at Kosin University Gospel Hospital from October 1996 to January 2005 were used for the study. RESULTS: We found a high prevalence of EGFR mutations and a low prevalence of KRAS mutations. EGFR mutations were present in 24% (25 of 104) of the samples: one mutation in exon 18, 13 in exon 19, one in exon 20, and 10 in exon 21. The presence of an EGFR mutation was not associated with gender, smoking history, histological grade, age, bronchioalveolar components, or cancer stage in patients with adenocarcinoma of the lung. CONCLUSIONS: Mutations of KRAS were present in 9.6% (9 of 94) of the samples: eight in codon 12 and one in codon 13. EGFR mutations were never found in tumors with KRAS mutations, suggesting a mutually exclusive relationship.

Photodynamic therapy in early lung cancer: a report of two cases.

Photodynamic therapy (PDT) that is based on the science of photochemistry has been recognized as a lung sparing local therapeutic modality that can achieve remarkable responses. It is an alternative treatment for early stage lung cancer patients who have poor lung function or multiple sites of cancer. Recently we treated a 70-year-old man who presented with squamous carcinoma in situ at a previous pneumonectomy site, and a 64-year-old man with a newly developed secondary superficial lung cancer, with PDT. There were no complications related to the procedure. Both patients had poor lung function due to prior lung cancer surgery. Clinical and histological complete remissions were achieved without any evidence of recurrence during 30 months of follow-up in both patients.

Detection of pre-invasive endobronchial tumors with D-light/autofluorescence system.

Autofluorescence bronchoscopy (AFB) is one of the newly developed diagnostic tools to detect the pre-cancerous lesions in the bronchial tissue. The utility of DLight/AFB in the detection of pre-cancerous lesions was compared to the standard white light bronchoscopy (WLB). In 113 patients (male 106, female 7), who visited hospital for evaluation of lung cancer, WLB and AFB were done and 364 biopsy specimens were obtained from November 2001 to August 2002. The bronchoscopic findings on WLB and AFB were compared to the pathological findings. The pathologic diagnoses of the specimens were as follows: normal in 96; hyperplasia in 69; metaplasia in 32; mild dysplasia in 13, moderate dysplasia in 6, severe dysplasia in 4; carcinoma in situ in 6; invasive carcinoma in 57. The relative sensitivity of adjunctive AFB to WLB vs. WLB alone was 1.5 in moderate dysplasia or worse lesions, and 3.2 in intraepithelial neoplasia. The specificity of adjunctive AFB and WLB alone were 0.91 and 0.5, respectively. The adjunctive AFB to the standard WLB increased the detection rate of the localized pre-invasive lesions. However, there was high rate of false positive in AFB.