Tae Hyun Um

Neonatal Hair Nicotine Levels and Fetal Exposure to Paternal Smoking at Home

Exposure to environmental tobacco smoke (ETS) is a major risk to human health, and the home is the greatest single source of ETS for children. The authors investigated fetal exposure to paternal smoking at home during pregnancy. Korean families were included as trios of fathers, mothers, and neonates identified in 2005-2007. Sixty-three trios were finally enrolled in this study after exclusion of those in which the mother was a smoker or was regularly exposed to ETS at places other than the home. Nicotine and cotinine concentrations in hair were measured by using liquid chromatography-tandem mass spectrometry to determine long-term exposure to ETS. The difference between neonatal nicotine concentrations in the smoker and nonsmoker groups was not statistically significant. However, in the indoor-smoker group, neonatal nicotine concentrations were significantly higher than in the outdoor and nonsmoker groups (P < 0.05). Furthermore, neonatal nicotine concentrations in the outdoor-smoker group were not different from those in the nonsmoker group. These findings indicate that paternal smoking inside the home leads to significant fetal and maternal exposure to ETS and may subsequently affect fetal health. Conversely, findings show that paternal smoking outside the home prevents the mother and her fetus from being exposed to ETS.

Prevalence and Distribution of Human Papillomavirus Infection in Korean Women as Determined by Restriction Fragment Mass Polymorphism Assay

The development of a prophylactic vaccine that targets human papillomaviruses (HPV) 6, 11, 16, and 18 to prevent cervical cancer has increased interest in the ethnic and geographical distributions of HPV genotypes. We investigated HPV prevalence and type distribution by restriction fragment mass polymorphism (RFMP) testing a total of 60,775 specimens (aged 18-79 yr, median 44) taken from liquid-based cytology. Overall HPV positive rate of total patients was 34.2%. Among the positive patients, 87.7% was single type infections, and 12.3% was multiple HPV types. HPV-16 was the most prevalent genotype observed in 2,307 (26.0%), followed by type 52 in 2,269 (25.5%), type 58 in 1,090 (12.3%), type 18 in 633 (7.1%), type 56 in 436 (4.9%). The pattern of high risk-HPV positive rate according to age showed U-shape with a peak in HPV prevalence among women less than 30 yr of age, and a second peak among the older females aged 70 to 79 yr. The leading four high-risk HPV genotypes were HPV-16, HPV-52, HPV-58, and HPV-18 in descending order. In conclusion, this study provides the most representative prevalence and type-specific distribution of HPV among Korean women, and demonstrates that the epidemiology of HPV infection is different from that of other regions of the world.

Serum BDNF Levels in Relation to Illness Severity, Suicide Attempts, and Central Serotonin Activity in Patients with Major Depressive Disorder: A Pilot Study

The aim of this study was to test the hypothesis that serum levels of brain-derived neurotrophic factor (BDNF) are correlated with the loudness dependence of auditory evoked potentials (LDAEP). The question of whether there is a difference in BDNF levels between depressive patients according to their illness severity, history of suicide attempts, and central serotonin activity was also addressed. A sample of 51 patients who met the criteria for major depressive disorder following diagnosis using axis I of the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders – text revision comprised the study subjects. The patients were stratified into two subgroups based on their illness severity, history of suicide attempts, and their LDAEP values. The LDAEP was evaluated by measuring the auditory event-related potentials, and serum BDNF was measured using blood sampling before beginning medication with serotonergic agents. There was no difference in serum BDNF levels between the two patient subgroups. The subgroup with moderate-to-severe depression (n = 16) was reanalyzed after stratifying it into two subgroups according to LDAEP and BDNF values (dichotomized at the medians into low and high). The high-LDAEP subgroup had higher serum BDNF levels and total Barratt Impulsiveness Scale score than the low-LDAEP subgroup (p = 0.03 and 0.036, respectively). Serum BDNF levels were positively correlated with LDAEP and total Beck Hopelessness Scale (BHS) score (r = 0.56, p = 0.025, and r = 0.59, p = 0.016, respectively). The high-BDNF subgroup had a higher LDAEP and total BHS score than the low-BDNF subgroup (p = 0.046 and p = 0.011, respectively). This is the first study to demonstrate a relationship between the BDNF level and LDAEP in Asian depressive patients. Intriguingly, the high-BDNF subgroup (divided according to illness severity) exhibited a more severe psychopathology on some psychometric rating scales, a finding that conflicts with previous results.

Eradication of Helicobacter pylori Increases Ghrelin mRNA Expression in the Gastric Mucosa

It has been suggested that Helicobacter pylori eradication may influence production of some peptides in the stomach, which can affect appetite. This hypothesis is controversial. To verify the hypothesis, we conducted this randomized controlled trial using H. pylori infected subjects without any gastrointestinal symptoms. The treatment group received triple H. pylori eradication therapy for 7 days and the control group received no medication. We measured ghrelin, obestatin and the tumor necrosis factor-α (TNF-α) mRNA levels in endoscopic biopsy specimens and the changes from baseline to follow-up. The plasma active n-octanoyl ghrelin and obestatin levels were measured in both groups. The ghrelin/obestatin ratios in plasma and gastric mRNA expression were calculated at baseline and follow-up. Ghrelin mRNA expression in the fundic mucosa after H. pylori eradication increased significantly compared to the control group (4.47±2.14 vs. 1.79±0.96, P=0.009), independent of inflammatory changes. However, obestatin mRNA expression decreased in the antral mucosa (-0.57±1.06 vs. 0.41±0.72, P=0.028). The treatment group showed a marginal increase (P=0.060) in plasma ghrelin/obestatin ratio. The TNF-α mRNA expression also decreased significantly with treatment. This randomized controlled trial demonstrates that H. pylori eradication increases ghrelin mRNA expression, independent of inflammatory cell changes.

Is plasma neutrophil gelatinase-associated lipocalin a predictive biomarker for acute kidney injury in sepsis patients? A systematic review and meta-analysis.

PURPOSE Neutrophil gelatinase-associated lipocalin (NGAL) is a useful biomarker for early diagnosis of acute kidney injury (AKI). However, the diagnostic value of NGAL for predicting AKI in sepsis patients is unclear. METHODS MEDLINE, EMBASE, and Cochrane Library databases were searched to identify research publications. RESULTS Twelve studies from 9 countries including a total of 1582 patients, of whom 315 (19.9%) developed AKI, were included in the study; plasma NGAL levels were significantly higher in adult sepsis patients with AKI than in those without AKI (mean difference, 274.65; 95% confidence interval [CI], 106.16-443.15; I(2) = 94%). Urine NGAL levels were not significantly different. The diagnostic odds ratio of plasma NGAL for predicting AKI in sepsis patients was 6.64 (95% CI, 3.80-11.58). The diagnostic accuracy of plasma NGAL was 0.881 (95% CI, 0.819-0.923) for sensitivity, 0.474 (95% CI, 0.367-0.582) for specificity, 0.216 (95% CI, 0.177-0.261) for positive predictive value and 0.965 (95% CI, 0.945-0.977) for negative predictive value. CONCLUSION Plasma NGAL has a high sensitivity and a high negative predictive value for detection of AKI in adult sepsis patients. However, its low specificity and low positive predictive value could limit its clinical utility. The usefulness of urine NGAL was not revealed in this study.

New allele-specific real-time PCR system for warfarin dose genotyping equipped with an automatic interpretative function that allows rapid, accurate, and user-friendly reporting in clinical laboratories

INTRODUCTION The optimal dose of the oral anticoagulant warfarin varies with polymorphisms of the vitamin K epoxide reductase complex subunit 1 (VKORC1) and cytochrome P450 2C9 (CYP2C9) genes. A fast and reliable method of warfarin dose adjustment is required to prevent serious hemorrhagic or thrombotic complications. The aim of this study is to develop and validate a new warfarin dose genotyping system with an automatic interpretation function. MATERIALS AND METHODS Four VKORC1 and two CYP2C9 SNPs were genotyped by real-time PCR using allele-specific primers and probes. Multiple reactions that included internal positive controls were performed in each well, and an automatic interpretative algorithm was developed. This system was validated using 82 clinical specimens previously genotyped by PCR-direct sequencing. The analytical time of the method was calculated. RESULTS No interference was observed when multiple samples were included in each reaction, with all internal positive control reactions being successful. In the genotyping algorithm, Ct differences <2 and ≥2 identified heterozygotes and homozygotes, respectively. All results obtained were concordant with those of the reference method. The overall analytical time for assay of 12 specimens was around 3 hours. CONCLUSION This rapid, accurate, and user-friendly genotyping system improves the efficacy and safety of anticoagulation therapy in clinical practice.

Clinical Characteristics of Vivax Malaria and Analysis of Recurred Patients

Background Plasmodium vivax malaria is an acute debilitating illness characterized by recurrent paroxysmal fever and relapses from hypnozoites in the liver. Although a few studies reported clinical characteristics of vivax malaria in civilians after reemergence in the Republic of Korea, only a small group of patients was analyzed. Materials and Methods We retrospectively reviewed the medical records of patients who had been diagnosed with vivax malaria by peripheral blood smear in a university-affiliated hospital located in a malaria-endemic area between January 2005 and December 2009. Results During the study period, a total of 352 malarial cases from 341 patients were diagnosed. Vivax malaria was most commonly developed in July and August, 24.7% (87/352), and 21.9% (77/352), respectively. The mean (SD) age was 42.5 (14.7) years and the number of male patients was 243 (71.3%). Six patients had a previous history of vivax malaria from 6 months to 10 years before. A total of 337 patients (98.8%) had fever and the mean (SD) body temperature was 38.3 (1.4)℃. Common associated symptoms were chills (213/341, 62.5%), headache (115/341, 33.7%), and myalgia (85/341, 24.9%). Laboratory findings included thrombocytopenia (340/341, 99.7%), anemia (97/341, 28.5%), leukopenia (148/341, 43.4%), increase of aspartate transaminase (177/341, 51.9%), and increase of alanine transaminase (187/341, 54.8%). Hypotension (14/341, 4.1%), altered mentality (3/341, 0.9%), azotemia (3/341, 0.9%), spleen infarction (2/341, 0.6%), and spleen rupture (1/341, 0.3%) developed as complications. Chloroquine was administered to all patients and primaquine was administered with mean (SD) 3.39 (0.82) mg/kg to 320 patients. There were 11 recurrent infections during the study period. The median (range) time to recurrent infection was 100 (32-285) days. Platelet counts were higher (86,550 vs. 56,910/mm3) and time to treatment of malaria was shorter (5 vs. 7 days) in relapsed cases compared with first occurrence cases (P=0.046). Conclusions The overall recurrence rate of vivax malaria was 3.2% (11/341) in this study. In recurred cases, malaria was diagnosed earlier and thrombocytopenia was less severe. To evaluate the risk factors associated with recurrence and adequate dose of primaquine in Korean patients, further large-scale prospective studies will be needed.

Splenic infarction in a patient with autoimmune hemolytic anemia and protein C deficiency

Splenic infarction is most commonly caused by cardiovascular thromboembolism; however, splenic infarction can also occur in hematologic diseases, including sickle cell disease, hereditary spherocytosis, chronic myeloproliferative disease, leukemia, and lymphoma. Although 10% of splenic infarction is caused by hematologic diseases, it seldom accompanies autoimmune hemolytic anemia (AIHA). We report a case of a 47-year-old woman with iron deficiency anemia who presented with pain in the left upper abdominal quadrant, and was diagnosed with AIHA and splenic infarction. Protein C activity and antigen decreased to 44.0% (60-140%) and 42.0% (65-140%), respectively. Laboratory testing confirmed no clinical cause for protein C deficiency, such as disseminated intravascular coagulation, sepsis, hepatic dysfunction, or acute respiratory distress syndrome. Protein C deficiency with splenic infarction has been reported in patients with viral infection, hereditary spherocytosis, and leukemia. This is a rare case of splenic infarction and transient protein C deficiency in a patient with AIHA.

Preschool children and their mothers are more exposed to paternal smoking at home than school children and their mothers

BACKGROUND Exposure to secondhand smoke (SHS) is a major risk to human health, and the home is the greatest single source of SHS in children. Here, the authors assessed SHS exposure of children and mothers by paternal smoking at home, and investigated how different this exposure is according to smoking location and childrens age. METHODS Two hundred-five families were enrolled in this study as trios of fathers, mothers, and children. Nicotine concentrations in hair were measured using liquid chromatography-tandem mass spectrometry to determine long-term exposure to SHS. RESULTS Differences between the smoker group and nonsmoker group in nicotine levels were statistically significant in both children and their mothers. However, difference between the indoor-smoker group and outdoor-smoker group was marginally significant in children and was not significant in their mothers. In the indoor-smoker group, preschool children and their mothers had nicotine concentrations about twice as high as school children and their mothers, respectively. In the outdoor-smoker group, however, differences between two age groups in nicotine levels were significant in preschool children, but not their mothers. CONCLUSION These findings indicate that paternal smoking at home leads to significant exposure to SHS in their children and spouses, which is not completely prevented by smoking outside. Especially, preschool children and their mothers appear to be most at risk for SHS exposure among nonsmoking household members.

Detection and identification of human papillomavirus using a PCR-restriction fragment mass polymorphism assay

A polymerase chain reaction-restriction fragment mass polymorphism (PCR-RFMP) assay protocol using PGMY09/11 primers for the detection and identification of human papillomavirus (HPV) has recently been developed. The present study evaluated the analytical sensitivity and clinical utility of HPV genotyping employing PCR-RFMP as compared to direct sequencing. Serial dilutions of cloned HPV DNA were analyzed in order to assess the limit of detection (LOD) and three sets of HPV clone mixtures (types 16+18, 16+11 and 18+11) were used to assess the accuracy of the genotyping assays. For 423 cervical specimens that were cytologically categorized as normal or cancer, the concordance between the two assays was evaluated. Clinical sensitivity was calculated by evaluating 101 histologically confirmed cases. The PCR-RFMP HPV assay had a lower LOD and 100% accuracy when detecting double HPV infection. Agreement between the two assays upon 423 clinical specimens was 91.0% with a κ-value of 0.86. The incidence of multiple HPV infections among HPV-positive patients was 19.0% by PCR-RFMP and 5.4% by sequencing. The clinical sensitivity of PCR-RFMP and sequencing was 92% and 84%, respectively. In conclusion, the PCR-RFMP assay for HPV genotyping correlated well with direct sequencing, provides high analytical and clinical sensitivity, and is advantageous in the detection of multiple HPV infections.