Association of Urinary N-Acetyl-β-D-Glucosaminidase with Cardiovascular Autonomic Neuropathy in Type 1 Diabetes Mellitus without Nephropathy

Background@#Cardiovascular autonomic neuropathy (CAN) is a common microvascular complication of diabetes and related to albuminuria in diabetic nephropathy (DN). Urinary N-acetyl-β-D-glucosaminidase (uNAG) is a renal tubular injury marker which has been reported as an early marker of DN even in patients with normoalbuminuria. This study evaluated whether uNAG is associated with the presence and severity of CAN in patients with type 1 diabetes mellitus (T1DM) without nephropathy. @*Methods@#This cross-sectional study comprised 247 subjects with T1DM without chronic kidney disease and albuminuria who had results for both uNAG and autonomic function tests within 3 months. The presence of CAN was assessed by age-dependent reference values for four autonomic function tests. Total CAN score was assessed as the sum of the partial points of five cardiovascular reflex tests and was used to estimatethe severity of CAN. The correlations between uNAG and heart rate variability (HRV) parameters were analyzed. @*Results@#The association between log-uNAG and presence of CAN was significant in a multivariate logistic regression model (adjusted odds ratio, 2.39; 95% confidence interval [CI], 1.08 to 5.28; P=0.031). Total CAN score was positively associated with loguNAG (β=0.261, P=0.026) in the multivariate linear regression model. Log-uNAG was inversely correlated with frequency-domain and time-domain indices of HRV. @*Conclusion@#This study verified the association of uNAG with presence and severity of CAN and changes in HRV in T1DM patients without nephropathy. The potential role of uNAG should be further assessed for high-risk patients for CAN in T1DM patients without nephropathy.

Association of Urinary N-Acetyl-β-D-Glucosaminidase with Cardiovascular Autonomic Neuropathy in Type 1 Diabetes Mellitus without Nephropathy

Background@#Cardiovascular autonomic neuropathy (CAN) is a common microvascular complication of diabetes and related to albuminuria in diabetic nephropathy (DN). Urinary N-acetyl-β-D-glucosaminidase (uNAG) is a renal tubular injury marker which has been reported as an early marker of DN even in patients with normoalbuminuria. This study evaluated whether uNAG is associated with the presence and severity of CAN in patients with type 1 diabetes mellitus (T1DM) without nephropathy. @*Methods@#This cross-sectional study comprised 247 subjects with T1DM without chronic kidney disease and albuminuria who had results for both uNAG and autonomic function tests within 3 months. The presence of CAN was assessed by age-dependent reference values for four autonomic function tests. Total CAN score was assessed as the sum of the partial points of five cardiovascular reflex tests and was used to estimatethe severity of CAN. The correlations between uNAG and heart rate variability (HRV) parameters were analyzed. @*Results@#The association between log-uNAG and presence of CAN was significant in a multivariate logistic regression model (adjusted odds ratio, 2.39; 95% confidence interval [CI], 1.08 to 5.28; P=0.031). Total CAN score was positively associated with loguNAG (β=0.261, P=0.026) in the multivariate linear regression model. Log-uNAG was inversely correlated with frequency-domain and time-domain indices of HRV. @*Conclusion@#This study verified the association of uNAG with presence and severity of CAN and changes in HRV in T1DM patients without nephropathy. The potential role of uNAG should be further assessed for high-risk patients for CAN in T1DM patients without nephropathy.

An Electronic Health Record-Integrated Computerized Intravenous Insulin Infusion Protocol: Clinical Outcomes and in Silico Adjustment

BACKGROUND: We aimed to describe the outcome of a computerized intravenous insulin infusion (CII) protocol integrated to the electronic health record (EHR) system and to improve the CII protocol in silico using the EHR-based predictors of the outcome.METHODS: Clinical outcomes of the patients who underwent the CII protocol between July 2016 and February 2017 and their matched controls were evaluated. In the CII protocol group (n=91), multivariable binary logistic regression analysis models were used to determine the independent associates with a delayed response (taking ≥6.0 hours for entering a glucose range of 70 to 180 mg/dL). The CII protocol was adjusted in silico according to the EHR-based parameters obtained in the first 3 hours of CII.RESULTS: Use of the CII protocol was associated with fewer subjects with hypoglycemia alert values (P=0.003), earlier (P=0.002), and more stable (P=0.017) achievement of a glucose range of 70 to 180 mg/dL. Initial glucose level (P=0.001), change in glucose during the first 2 hours (P=0.026), and change in insulin infusion rate during the first 3 hours (P=0.029) were independently associated with delayed responses. Increasing the insulin infusion rate temporarily according to these parameters in silico significantly reduced delayed responses (P<0.0001) without hypoglycemia, especially in refractory patients.CONCLUSION: Our CII protocol enabled faster and more stable glycemic control than conventional care with minimized risk of hypoglycemia. An EHR-based adjustment was simulated to reduce delayed responses without increased incidence of hypoglycemia.

Clarithromycin-Based Standard Triple Therapy Can Still Be Effective for Helicobacter pylori Eradication in Some Parts of the Korea

We evaluated the antibiotic resistance rates and eradication rates of clarithromycin based triple therapy from 2005 to 2010 retrospectively. In addition, we investigated the mechanism of clarithromycin resistance in Helicobacter pylori strains isolated from Korean patients. Two hundred and twelve strains of H. pylori were isolated from 204 patients. H. pylori ATCC 43504 was used as the standard strain. The eradication rates of H. pylori from 2005 to 2010 were 89.3%, 82.6%, 86.3%, 87.7%, 81.8%, and 84.2%, respectively. Total eradication rate was 84.9%. DNA sequences of the 23S RNA gene in clarithromycin-resistant strains were determined. The resistance rates of H. pylori to amoxicillin, clarithromycin, metronidazole, tetracycline, ciprofloxacin, moxifloxacin, and levofloxacin were 9.0%, 8.5%, 36.3%, 0%, 14.2%, 14.2%, and 14.2%, respectively. The multidrug resistance rate of H. pylori was 16.5%. Sequence analysis of clarithromycin-resistant strains showed an A2144G mutation in 8 of 14 strains (57.1%), a T2183C mutation in 5 of 14 strains (35.7%), and double mutations of both A2144G and T2183C in 1 of 14 strains (7.1%). In the present study, triple therapy may still be an effective eradication therapy for H. pylori infections in Korea. The A2144G and T2183C mutations are mainly present in clarithromycin-resistant isolates.

Systemic Amyloidosis Manifested by Gastric Outlet Obstruction

Amyloidosis is characterized by extracellular deposition of insoluble protein fibrils that stain with Congo red application and appear apple green under polarized light. The presenting symptoms result from the involvement of many affected, nonspecific and generalized organ systems. Our patient was an 80-year-old woman with no medical history. She presented with a 2-week history of nausea and vomiting. An esophagogastroduodenoscopy showed erythematous and edematous mucosa on the antrum with pyloric stenosis. Histopathologic examination of the biopsy specimen showed the deposition of amorphous, homogeneous, and acidophilic material in the gastric mucosa. Amyloidal protein was proven by positive Congo red stain. A serum and urine immunfixation electrophoresis showed lambda light chain band. She developed symptoms of repeated greenish color vomiting. A follow-up esophagogastroduodenoscopy showed progressed antral obstruction. However, she refused further evaluation and treatment and was managed conservatively. She later died of disease progression after 34 hospital days.

Silicosis Caused by Chronic Inhalation of Snail Shell Powder

A 70-yr-old woman visited our hospital for shortness of breath. Chest CT showed ground glass opacity and traction bronchiectasis at right middle, lower lobe and left lingular division. Video-assisted thoracic surgical biopsy at right lower lobe and pathologic examination revealed mixed dust pneumoconiosis. Polarized optical microscopy showed lung lesions were consisted of silica and carbon materials. She was a housewife and never been exposed to silica dusts occupationally. She has taken freshwater snails as a health-promoting food for 40 yr and ground shell powder was piled up on her backyard where she spent day-time. Energy dispersive X-ray spectroscopy of snail shell and scanning electron microscopy with energy dispersive x-ray spectroscopy of lung lesion revealed that silica occupies important portion. Herein, we report the first known case of silicosis due to chronic inhalation of shell powder of freshwater snail.

H1N1 Influenza/A Associated ARDS Recovered without Mechanical Ventilatory Support: A Case Report / 대한구급학회지

An eighteen year-old female visited the ER in our hospital with fever of 38.5degrees C for 2 days. She also had cough, myalgia, and dyspnea. Chest PA and lung HRCT showed mild pulmonary edema at both hilar areas. However, she had severe hypoxia (PaO2; 58 mmHg in room air). RT-PCR for H1N1 influenza/A of pharyngeal swab was positive. Tamiflu (150 mg/d) with broad-spectrum antibiotics was prescribed. Two days later, her dyspnea aggravated and chest PA showed diffuse bilateral infiltration. PaO2 dropped to 70 mmHg (O2 10 L/min by face mask with reservoir bag). She was transferred to the MICU and the Tamiflu dose was doubled (300 mg/day). Mechanical ventilator was set aside to prepare respiratory failure. Fortunately, her symptoms and oxygenation improved and she was discharged with full recovery. Although, most cases of ARDS require mechanical ventilatory support, early and adequate dose of Tamiflu may avoid it in the case of ARDS developed by H1N1 influenza/A.

Allergic Bronchopulmonary Aspergillosis Coupled with Sinusitis in a Nonasthmatic Patient / 결핵및호흡기질환

Allergic bronchopulmonary aspergillosis (ABPA) is a complex clinical entity resulting from an allergic immune response to Aspergillus species, and most often occurs in patients with asthma. ABPA is rarely observed in the absence of asthma, which is, in fact, the principal criterion for its diagnosis. Our patient was a 53-year-old woman with no history of bronchial asthma. She presented with a 1-month history of cough, mucopurulent nasal discharge, and localized pulmonary consolidation. Peripheral blood eosinophilia and elevated serum IgE were observed. Sinus radiography showed right maxillary sinusitis. Pathologic examination of bronchoscopic biopsy specimens revealed conglomerates of fungal hyphae. Pulmonary function and bronchial provocation tests were within normal ranges. The patient was successfully treated for 3 months with itraconazole and oral prednisolone. There has been no evidence of recurrence over a 7-month follow-up. ABPA coupled with sinusitis in a nonasthmatic patient is a very rare occurrence and warrants reporting.

Cell Differentiation Might Predict the Recurrence in Surgically Resected Non-Small Cell Lung Carcinoma / 결핵및호흡기질환

BACKGROUND: Lung cancer is the most common cause of cancer mortality in Korea. The TNM stage at presentation in patients with non-small cell lung cancer (NSCLC) has the greatest impact on prognosis. Patients who undergo a complete resection for NSCLC are likely to develop recurrent and/or metastatic disease. There are several factors influencing the development of recurrence. We explored risk factors of recurrence in patients with stages I and II NSCLC, who had undergone curative resection. METHODS: We reviewed patients who had complete surgical resection as definitive treatment for stage I or II. Patients followed up for more than 36 months. We evaluated several factors which might have relationship with recurrence, such as patient's demographic factors, TNM staging, pathologic finding, tumor markers and surgical technique. RESULTS: A total of 75 patients were enrolled for analysis, of whom 58 were men and 17 were women with mean age of 61 (range, 37 to 76) years. The average size of tumors was 3.9 cm (0.7 to 10 cm). There were 64 patients with stage I NSCLC and 11 with stage II NSCLC. Among 64 patients with stage I NSCLC, 35 patients showed recurrences whereas 8 patients have recurred in stage II NSCLC. Grade of differentiation of tumor was closely related to the recurrence. Seventy-five percent of patients who had poor tumor differentiation experienced a recurrence. In contrast, 3 patients of twelve had recurrences, who revealed differentiation in their tissue (p<0.05). CONCLUSION: Tumor differentiation could be a predictive factor for tumor recurrence in patients who have undergone curative resection for stage I or II NSCLC.

Association of Polymorphisms in the Prostate-Specific Antigen (PSA) Gene Promoter with Serum PSA Level and PSA Changes after Dutasteride Treatment in Korean Men with Benign Prostatic Hypertrophy

PURPOSE: Studies of genetic variation in the prostate-specific antigen (PSA) gene have improved the diagnostic accuracy of PSA for diagnosing prostate diseases in Caucasians. However, the reference ranges and pharmacokinetics of PSA differ significantly according to race. Therefore, we evaluated the association between genetic variations in the PSA promoter area and benign prostatic hyperplasia (BPH) phenotypes in Korean BPH patients. MATERIALS AND METHODS: One hundred twenty-one men were enrolled. The initial serum PSA level, prostate size, and PSA changes at 3 months after treatment with dutasteride were determined. We amplified the promoter region of the PSA gene (nucleotide positions -158 to -356 and -5217 to -5429) and sequenced the products. RESULTS: Three relatively well characterized single-nucleotide polymorphisms (SNPs; rs3760722, rs266867, and rs266868), six uncharacterized SNPs (rs17554958, rs266882, rs4802754, rs2739448, rs2569733, and rs17526278), and one novel SNP (nucleotide position -5402) were found. There were no statistically significant correlations between any of the SNPs of the PSA promoter area and age-adjusted prostate sizes, initial PSA levels, or PSA variations after 3 months of dutasteride treatment. CONCLUSIONS: SNPs in the PSA promoter area were not associated with BPH phenotypes. We could not predict serum PSA changes after dutasteride treatment on the basis of PSA promoter genotype in Korean patients with BPH.

The Effect of Epigallocatechin-3-gallate on HIF-1alpha and VEGF in Human Lung Cancer Cell Line / 결핵및호흡기질환

BACKGROUND: Epigallocatechin-3-gallate (EGCG) is the major catechin in green tea, and has shown antiproliferative, antiangiogenic, antimetastatic and cell cycle pertubation activity in various tumor models. Hypoxia can be induced because angiogenesis is insufficient for highly proliferating cancer. Hypoxia-inducible factor-1alpha (HIF-1alpha) and its downstream target, vascular endothelial growth factor (VEGF), are important for angiogenesis, tumor growth and metastasis. The aim of this study was to determine how hypoxia could cause changes in the cellular phenomena and microenvironment in a non-small cell culture system and to examine the effects of EGCG on a HIF-1alpha and VEGF in A549 cell line. METHODS: A549 cells, a non-small cell lung cancer cell line, were cultured with DMEM and 10% fetal bovine serum. A decrease in oxygen tension was induced using a hypoxia microchamber and a CO2-N2 gas mixture. Gas analysis and a MTT assay were performed. The A549 cells were treated with EGCG (0, 12.5, 25, 50 micromol/L), and then examined by real-time-PCR analysis of HIF-1alpha, VEGF, and beta-actin mRNA. RESULTS: Hypoxia reduced the proliferation of A549 cells from normoxic conditions. EGCG inhibited HIF-1alpha transcription in A549 cells in a dose-dependent manner. Compared to HIF-1alpha, VEGF was not inhibited by EGCG. CONCLUSION: HIF-1alpha can be inhibited by EGCG. This suggests that targeting HIF-1alpha with a EGCG treatment may have therapeutic potential in non-small cell lung cancers.

The Usefulness of Whole-blood Interferon-gamma Release Assay for the Diagnosis of Extra-pulmonary Tuberculosis / 결핵및호흡기질환

BACKGROUND: The whole-blood interferon-gamma release assay (QuantiFERON-TB Gold [QFT-G]: Cellestis, Carnegie, Victoria, Australia) has been studied primarily for the use of diagnosing active pulmonary tuberculosis (TB) or latent TB. In the present study, the usefulness of QFT-G was evaluated for the diagnosis of extra-pulmonary tuberculosis (EP-TB). METHODS: From June 2006 to February 2009, we evaluated the usefulness of QFT-G in patients (n=65) suspected with EP-TB, retrospectively. The diagnostic sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the QFT-G assay were analyzed. RESULTS: EP-TB was diagnosed in 33 (51%) participants. The overall sensitivity, specificity, PPV, and NPV of the QFT-G assay for EP-TB were 78%, 79%, 81%, and 77%, respectively. Of the 33 with EP-TB, 14 (42%) were diagnosed with TB pleurisy, 7 (21%) with TB lymphadenitis, 7 (21%) with intestinal TB, and 5 (15%) with EP-TB in other sites. In subgroup analyses according by site of infection, the QFT-G showed 86% sensitivity, 64% specificity, and 78% NPV in TB pleurisy. On the other hand, the sensitivity, specificity, and NPV of the assay were 71%, 83% and 71%, respectively in TB lymphadenitis, and 86%, 100% and 88%, respectively in intestinal TB. Among the patients with suspected alternative site EP-TB, the sensitivity, specificity, and NPV of the assay were 50%, 80% and 67%, respectively. CONCLUSION: The QFT-G assay showed moderate diagnostic accuracy in EP-TB. However, negative QFT-G assay does not exclude EP-TB because of the low NPV of this assay.

A Questionnaire Study Concerning Circumcision of Elementary School Boys in the City of Gwangju / 대한비뇨기과학회지

PURPOSE: Circumcision is widely practiced in Korea, but its implementation is still controversial, especially among younger parents. Using a questionnaire study, we tried to determine the rate of circumcision among elementary school boys and to determine parental concerns about phimosis and circumcision. We then compared our findings with previously published literature. MATERIALS AND METHODS: Between May and June 2007, we randomly selected five elementary schools and distributed self-administered questionnaires to the parents of 2,712 boys from these schools. Questions were related to children's circumcision status, age at the time of circumcision, and opinions concerning circumcision, such as its necessity and benefits. Completed questionnaires were collected and analyzed. RESULTS: The response rate was 66.2%. The overall circumcision rate of boys in elementary school was 15.4%. Some 40.3% of those boys underwent circumcision in the neonatal period, and 37.3% underwent the procedure between ages 9 and 12 years. The circumcision rate was significantly higher in boys in the higher income bracket group(29.5%) compared to boys in the middle and low income bracket groups(15.4% and 12.8%, respectively). Most boys were circumcised based on the intent of their parents(64.2%). Some 44.5% of parents believed that circumcision was necessary, while 36.3% of parents believed it was not necessary. The most common motive for circumcision was "hygiene benefits"(80.2%). CONCLUSIONS: The rates of actual circumcision practice and of approval of circumcision were lower in this report compared to previous reports. It seems that more clinical research on circumcision is needed. Physicians should provide information about circumcision to boys and their parents.