Unfavorable effect of high postoperative fluid balance on outcome of pancreaticoduodenectomy

Purpose@#Despite the many efforts to overcome postoperative complications, pancreaticoduodenectomy (PD) is still accompanied with considerable concerns of lethal complications. The clinical factors are known to affect postoperative outcomes such as diameter of pancreatic duct, texture of pancreas, and comorbidity of the patients are mostly uncorrectable. Thus, investigation for correctable risk factors is required. Recently, perioperative fluid volume was reported to be associated with complications after PD. This study aims to determine the relationship between postoperative fluid balance and surgical outcome after open PD. @*Methods@#We reviewed, retrospectively, 172 consecutive patients who underwent open PD in a single institution between 2015 and 2019. The status of perioperative fluid balance 2 days after surgery and clinical factors were investigated to determine the association with postoperative outcome including postoperative pancreatic fistula (POPF). According to postoperative fluid balance, patients were divided into high- and low-balance groups, and clinical features and surgical outcomes were compared between both groups. Multivariate analysis were performed to identify risk factors for POPF. @*Results@#The percentage of morbidity and the incidence of POPF were higher in the high-balance group compared to the low-balance group (61.6% vs. 37.2%, P = 0.001; 15.1% vs. 3.5%, P = 0.009). High postoperative fluid balance and the presence cardiovascular disease were correlated with POPF on multivariate analysis (odds ratio [OR], 4.574; 95% confidence interval [CI], 1.229–17.029; P = 0.023 and OR, 3.517; 95% CI, 1.209–12.017; P = 0.045). @*Conclusion@#Higher amount of postoperative fluid balance and the presence of cardiovascular disease are associated with POPF after PD.

Various types of reconstruction after pancreaticoduodenectomy for the patients who underwent all types of gastrectomy: a single-center experience

Purpose@#The incidence of patients requiring pancreaticoduodenectomy (PD) following any type of gastrectomy is increasing as the population of elderly patients is increasing, especially in endemic areas of gastric cancer such as Korea. All types of gastrectomy can be categorized as subtotal gastrectomy with Billroth I (BI), Billroth II (BII), and total gastrectomy with Roux-en-Y anastomosis. In this paper, we reviewed our experiences of PD for patients who previously underwent gastrectomy. @*Methods@#We reviewed the medical records of the patients who underwent PD following any type of gastrectomy among 505 consecutive patients who underwent PD in a single institution between 2011 and 2020 retrospectively. @*Results@#There were 13 patients who had undergone gastrectomy including 7 patients of BI, 1 patient of BII, and 5 patients of total gastrectomy. For all 7 patients of BI, the reconstruction was not different from conventional PD. For the 1 patient of BII, previous gastrojejunal anastomosis was preserved and reconstruction was performed in Roux-en-Y method. For the 5 patients with total gastrectomy, 2 different types of reconstruction were performed. In one patient, we removed the remaining jejunum with the specimen, and reconstruction was performed. For the other 4 patients, the remaining jejunum, distal to the Treitz ligament, was preserved and was utilized for anastomosis. Surgeries for all patients were uneventful. @*Conclusion@#PD following any type of gastrectomy can be safe. Especially, if the length of remained jejunum is long enough, its utilization for the reconstruction can be an appropriate option.

Current Status of Low-Density Lipoprotein Cholesterol Target Achievement in Patients with Type 2 Diabetes Mellitus in Korea Compared with Recent Guidelines

Background@#We evaluated the achievement of low-density lipoprotein cholesterol (LDL-C) targets in patients with type 2 diabetes mellitus (T2DM) according to up-to-date Korean Diabetes Association (KDA), European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS), and American Diabetes Association (ADA) guidelines. @*Methods@#This retrospective cohort study collected electronic medical record data from patients with T2DM (≥20 years) managed by endocrinologists from 15 hospitals in Korea (January to December 2019). Patients were categorized according to guidelines to assess LDL-C target achievement. KDA (2019): Very High-I (atherosclerotic cardiovascular disease [ASCVD]) <70 mg/dL; Very High-II (target organ damage [TOD], or cardiovascular risk factors [CVRFs]) <70 mg/dL; high (others) <100 mg/dL. ESC/EAS (2019): Very High-I (ASCVD): <55 mg/dL; Very High-II (TOD or ≥3-CVRF) <55 mg/dL; high (diabetes ≥10 years without TOD plus any CVRF) <70 mg/dL; moderate (diabetes <10 years without CVRF) <100 mg/dL. ADA (2019): Very High-I (ASCVD); Very High-II (age ≥40+ TOD, or any CVRF), for high intensity statin or statin combined with ezetimibe. @*Results@#Among 2,000 T2DM patients (mean age 62.6 years; male 55.9%; mean glycosylated hemoglobin 7.2%) ASCVD prevalence was 24.7%. Of 1,455 (72.8%) patients treated with statins, 73.9% received monotherapy. According to KDA guidelines, LDL-C target achievement rates were 55.2% in Very High-I and 34.9% in Very High-II patients. With ESC/EAS guidelines, target attainment rates were 26.6% in Very High-I, 15.7% in Very High-II, and 25.9% in high risk patients. Based on ADA guidelines, most patients (78.9%) were very-high risk; however, only 15.5% received high-intensity statin or combination therapy. @*Conclusion@#According to current dyslipidemia management guidelines, LDL-C goal achievement remains suboptimal in Korean patients with T2DM.

Nutritional Therapy Related Complications in Hospitalized Adult Patients: A Korean Multicenter Trial

PURPOSE: Nutritional therapy (NT), such as enteral nutrition (EN) or parenteral nutrition (PN), is essential for the malnourished patients. Although the complications related to NT has been well described, multicenter data on symptoms in the patients with receiving NT during hospitalization are still lacking. METHODS: Nutrition support team (NST) consultations, on which NT-related complications were described, were collected retrospectively for one year. The inclusion criteria were patients who were (1) older than 18 years, (2) hospitalized, and (3) receiving EN or PN at the time of NST consultation. The patients' demographics (age, sex, body mass index [BMI]), type of NT and type of complication were collected. To compare the severity of each complication, the intensive care unit (ICU) admission, hospital stay, and type of discharge were also collected. RESULTS: A total of 14,600 NT-related complications were collected from 13,418 cases from 27 hospitals in Korea. The mean age and BMI were 65.4 years and 21.8 kg/m2. The complications according to the type of NT, calorie deficiency (32.4%, n=1,229) and diarrhea (21.6%, n=820) were most common in EN. Similarly, calorie deficiency (56.8%, n=4,030) and GI problem except for diarrhea (8.6%, n=611) were most common in PN. Regarding the clinical outcomes, 18.7% (n=2,158) finally expired, 58.1% (n=7,027) were admitted to ICU, and the mean hospital days after NT-related complication were 31.3 days. Volume overload (odds ratio [OR]=3.48) and renal abnormality (OR=2.50) were closely associated with hospital death; hyperammonemia (OR=3.09) and renal abnormality (OR=2.77) were associated with ICU admission; “micronutrient and vitamin deficiency” (geometric mean [GM]=2.23) and volume overload (GM=1.61) were associated with a longer hospital stay. CONCLUSION: NT may induce or be associated with several complications, and some of them may seriously affect the patient's outcome. NST personnel in each hospital should be aware of each problem during nutritional support.

Feasibility Study of Physician Orders for Life-Sustaining Treatment for Patients with Terminal Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Physician Orders for Life-Sustaining Treatment (POLST) form is a legal document for terminally ill patients to make medical decisions with physicians near the end-of-life. A multicenter prospective study was conducted to evaluate the feasibility of POLST administration in actual oncological practice. MATERIALS AND METHODS: Patients with terminal cancer, age ≥ 20 years, and capable of communicating were eligible. The primary endpoint was the completion rate of POLST. Data about physicians' or patients' barriers were also collected. RESULTS: From June to December 2017, 336 patients from seven hospitals were eligible. Median patient age was 66 years (range, 20 to 94 years); 52.7% were male; and 60.4% had poor performance status. Primary cancer sites were hepato-pancreato-biliary (26.2%), lung (23.2%), and gastrointestinal (19.9%). Expected survival duration was 10.6±7.3 weeks, with 41.2% receiving hospice care, 37.9% showing progression after cancer treatment, and the remaining patients were under active treatment (15.8%) or initially diagnosed with terminal cancer (5.1%). POLST forms were introduced to 60.1% of patients, and 31.3% signed the form. Physicians' barriers were reluctance of family (49.7%), lack of rapport (44.8%), patients' denial of prognosis (34.3%), lack of time (22.7%), guilty feelings (21.5%), and uncertainty about either prognosis (21.0%) or the right time to discuss POLST (16.6%). The patients' barriers were the lack of knowledge/understanding of POLST (65.1%), emotional discomfort (63.5%), difficulty in decision-making (66.7%), or denial of prognosis (14.3%). CONCLUSION: One-third of patients completed POLST forms, and various barriers were identified. To overcome such barriers, social engagement, education, and systematic support might be necessary.

Associations between the HaeIII Single Nucleotide Polymorphism in the SLC2A1 Gene and Diabetic Nephropathy in Korean Patients with Type 2 Diabetes Mellitus

BACKGROUND: Diabetic nephropathy (DN) is the most serious microvascular complication of diabetes mellitus and is one of the leading causes of end stage renal failure. In previous studies, the contribution of genetic susceptibility to DN showed inconsistent results. In this study, we investigated the association between the solute carrier family 2 facilitated glucose transporter member 1 (SLC2A1) HaeIII polymorphism and DN in Korean patients with type 2 diabetes mellitus (T2DM) according to disease duration. METHODS: A total of 846 patients with T2DM (mean age, 61.3 ± 12.3 years; mean duration of T2DM, 10.3 ± 7.9 years; 55.3% men) who visited the Chungbuk National University Hospital were investigated. The HaeIII polymorphism of the SLC2A1 gene was determined by the real time polymerase chain reaction method. Genotyping results were presented as GG, AG, or AA. A subgroup analysis was performed according to duration of T2DM (≤ 10 years, < 10 years). RESULTS: The AG + AA genotype showed a significantly higher risk of DN compared with the GG genotype in patients with a type 2 DM duration less than 10 years (12.4% vs. 4.2%; P < 0.001). No significant differences were observed in terms of other diabetic complications, including retinopathy, peripheral neuropathy, cardiovascular disease, cerebrovascular disease or peripheral artery disease, according to the genotypes of the SLC2A1 HaeIII polymorphism. CONCLUSION: The SLC2A1 HaeIII polymorphism was associated with DN in Korean patients with T2DM, particularly in the group with a relatively short disease duration.

Prevalence of Malnutrition in Hospitalized Patients: a Multicenter Cross-sectional Study

BACKGROUND: Malnutrition is associated with many adverse clinical outcomes. The present study aimed to identify the prevalence of malnutrition in hospitalized patients in Korea, evaluate the association between malnutrition and clinical outcomes, and ascertain the risk factors of malnutrition. METHODS: A multicenter cross-sectional study was performed with 300 patients recruited from among the patients admitted in 25 hospitals on January 6, 2014. Nutritional status was assessed by using the Subjective Global Assessment (SGA). Demographic characteristics and underlying diseases were compared according to nutritional status. Logistic regression analysis was performed to identify the risk factors of malnutrition. Clinical outcomes such as rate of admission in intensive care units, length of hospital stay, and survival rate were evaluated. RESULTS: The prevalence of malnutrition in the hospitalized patients was 22.0%. Old age (≥ 70 years), admission for medical treatment or diagnostic work-up, and underlying pulmonary or oncological disease were associated with malnutrition. Old age and admission for medical treatment or diagnostic work-up were identified to be risk factors of malnutrition in the multivariate analysis. Patients with malnutrition had longer hospital stay (SGA A = 7.63 ± 6.03 days, B = 9.02 ± 9.96 days, and C = 12.18 ± 7.24 days, P = 0.018) and lower 90-day survival rate (SGA A = 97.9%, B = 90.7%, and C = 58.3%, P < 0.001). CONCLUSION: Malnutrition was common in hospitalized patients, and resulted in longer hospitalization and associated lower survival rate. The rate of malnutrition tended to be higher when the patient was older than 70 years old or hospitalized for medical treatment or diagnostic work-up compared to elective surgery.

Association of Adiponectin 45T/G Polymorphism with Diabetic Cardiovascular Complications in Korean Type 2 Diabetes

BACKGROUND: Adiponectin is an adipokine that regulates lipid and glucose metabolism and has been shown to have anti-inflammatory and anti-atherogenic effects. It also plays an important role in the development of cardiovascular disease (CVD). METHODS: This study evaluated the association between adiponectin 45T/G polymorphism and cardiovascular complication in type 2 diabetes in Koreans. RESULTS: The present study included 758 patients with type 2 diabetes. The distribution of the adiponectin 45T/G polymorphism was 3.56% (n = 27) for GG, 42.35% (n = 321) for TG, and 54.09% (n = 410) for TT in patients with type 2 diabetes. The prevalence of CVD was significantly higher in subjects with the GG + TG genotype compared to those with the TT genotype (17.5% vs. 9.8%, P = 0.002). The G allele was associated with a higher risk of CVD (P = 0.002). CONCLUSION: Our findings suggest that the adiponectin 45T/G polymorphism is associated with diabetic cardiovascular complication in type 2 diabetes.

Association between Bsm1 Polymorphism in Vitamin D Receptor Gene and Diabetic Retinopathy of Type 2 Diabetes in Korean Population

BACKGROUND: Type 2 diabetes is one of the most common diseases with devastating complications. However, genetic susceptibility of diabetic complications has not been clarified. The vitamin D endocrine system is related with calcification and lipolysis, insulin secretion, and may be associated with many complicated disease including diabetes and cardiovascular disease. Recent studies reported that single nucleotide polymorphisms of vitamin D receptor (VDR) gene were associated with diabetic complications. METHODS: In present study, we evaluated the association of BsmI polymorphism of VDR with diabetic complications in Korean diabetes patients. Total of 537 type 2 diabetic subjects from the Endocrinology Clinic of Chungbuk National University Hospital were investigated. Polymerase chain reaction-restriction fragment length polymorphism was used to test the genotype and allele frequency of BsmI (rs1544410; BB, Bb, bb) polymorphisms. RESULTS: Mean age was 62.44+/-10.64 years and mean disease duration was 13.65+/-7.39 years. Patients with B allele (BB or Bb) was significantly associated with lower risk of diabetic retinopathy (severe non-proliferative diabetic retinopathy or proliferative retinopathy; 7.4%, 5/68) compared with patients without B allele (bb; 17.3%, 81/469; P=0.035). This association was also significant after adjusting for hemoglobin A1c level, body mass index, age, sex, and diabetes mellitus duration, concurrent dyslipidemia and hypertension (odds ratio, 2.99; 95% confidence interval, 1.08 to 8.29; P=0.035) in logistic regression analysis. CONCLUSION: Our findings suggest that B allele of Bsm1 polymorphism in VDR gene is associated with lower risk of diabetic retinopathy in type 2 diabetic patients. Bsm1 genotype could be used as a susceptibility marker to predict the risk of diabetes complication.

Polyarteritis nodosa presented as a dilatation of the intrahepatic bile duct

Polyarteritis nodosa (PAN) is a systemic necrotizing vasculitis of small- and medium-sized arteries in multiorgan systems. PAN may affect the gastrointestinal tract in 14%-65% of patients, but rarely involves the biliary tract and liver. We describe a patient without underlying disease who was diagnosed with PAN during resection of the gallbladder and liver.

Association of Monocyte Chemoattractant Protein-1 (MCP-1) 2518A/G Polymorphism with Proliferative Diabetic Retinopathy in Korean Type 2 Diabetes

PURPOSE: Monocyte chemoattractant protein-1 (MCP-1) is a chemokine that can increase adhesion molecule expression on monocytes and produce superoxide anions. Hyperglycemia induces MCP-1 production in vascular endothelial cells and retinal pigmented epithelial cells, and has been implicated as a causal factor in the facilitation of vascular complications in diabetes. In the present study, we evaluated the association of a single nucleotide polymorphism (SNP) in the MCP-1 gene with proliferative diabetic retinopathy (PDR) in a Korean population with type 2 diabetes. MATERIALS AND METHODS: We conducted a case-control study, which enrolled 590 subjects with type 2 diabetes, and SNP genotyping of c.2518A/G in the MCP-1 gene was performed using polymerase chain reaction followed by digestion with PvuII restriction enzyme. RESULTS: The prevalence of c.2518A/G polymorphism in diabetic patients was 13.2% (A/A), 47.1% (A/G) and 39.7% (G/G). In patients with diabetic retinopathy, the prevalence of PDR was significantly higher (p=0.009) in diabetic subjects with the c.2518A/A genotype (35.9%; n=78) compared to those with either the A/G or G/G genotype (22.3%, n=512). The prevalence of any other micro and macro-complications, including nephropathy and cerebrovascular events, were not different according to the c.2518A/G genotype. CONCLUSION: Our new genetic findings suggest that the c.2518A/A genotype in MCP-1 could be used as a susceptibility gene to predispose Koreans exhibiting type 2 diabetes for the development of PDR.

Prospective Observation of 5-Year Clinical Course of Subclinical Hypothyroidism in Korean Population

Subclinical hypothyroidism (SCH) is a common clinical condition, whereas it's natural course has not been identified distinctly. We evaluated the natural history of 169 SCH patients over 5-yr and the prognostic factors including thyroid autoantibodies and thyroid ultrasonographic (USG) findings related to develop overt hypothyroidism. After 5 yr, 47.3% of patients showed normalization of TSH, while 36.7% of patients remained persistence of high level of TSH, and overt hypothyroidism developed in 11.2% of patients. There were painless thyroiditis (2.9%) and hyperthyroidism (1.7%) during 5 yr follow-up. The thyroid nodule was seen in 48.6% of patients. Most of patients had 1 to 2 nodules whereas only 3% of patients with thyroid nodule had more than 6 nodules. Overt hypothyroidism patients had more heterogenous echogenecity in USG compared to patients with normalization or persistent SCH (76.5% vs 50.0% vs 35.0%, P = 0.048) and higher prevalence positive anti-thyroid peroxidase (anti-TPO Ab) and anti-thyroglobulin antibody (anti-Tg Ab) and titer of anti-TPO Ab than other two groups. The cut off values for prediction of overt hypothyroidism were TSH > 7.45 microIU/mL, free T4 560 IU/mL. SCH has various courses and initial TSH, free T4, presence of thyroid autoantibody, titer of thyroid autoantibody; and thyroid USG findings can serve as a prognostic factor for progression of overt hypothyroidism. These parameters suggest consideration to initiate thyroid hormone treatment in SCH.

Bowel infarction due to intestinal mucormycosis in an immunocompetent patient / 대한외과학회지

Mucormycosis is a fatal opportunistic fungal infection that typically occurs in immunocompromised patients. The classical manifestation of mucormycosis is a rhinocerebral infection, and although primary gastrointestinal infection is uncommon, it has an extremely high mortality rate in immunocompromised patients. Furthermore, cases of gastrointestinal mucormycosis in an immunocompetent host are rarely reported. Here, we describe our experience of a male patient, with no underlying disease, who succumbed to a bowel infarction caused by intestinal mucormycosis during mechanical ventilatory care for severe pneumonia and septic shock.

A Case of Lingual Thyroid Treated by 131I Ablation

A lingual thyroid is a rare developmental anomaly caused by the failure of the descent of the thyroid gland anlage early in the course of embryogenesis. The incidence of lingual thyroid has been reported to be 1/100,000. Lingual thyroid is often asymptomatic but may cause dysphagia, dysphonia, upper airway obstruction and hemorrhage. In this report, we described the case of a 50-year-old women experiencing lingual thyroid who had subclinical hypothyroidism. She underwent successful 131I ablation and has done well on thyroid hormone replacement therapy.

Diabetes Education Recognition Program / 임상당뇨병

The Committee of Education of the Korean Diabetes Association discussed the need to develop the Diabetes Education Recognition Program. In 2011, the current certification program was reviewed and a survey was conducted to improve the Diabetes Education Recognition Program. This improved program will be a standard for qualified diabetes education for diabetes educators and institutes, and will ultimately become a national standard for diabetes education.

A Case of Cushing's Disease in Pregnancy

Developing Cushing's syndrome during pregnancy is rare because menstruation is irregular and hypercortisolism causes infertility. Developing Cushing's disease during pregnancy is very rare because there is even less ovulation than those with the adrenal adenoma. The clinical manifestations of Cushing's syndrome may easily be missed during pregnancy as the features of weight gain, hypertension, and hyperglycemia overlap with those that occur during a pregnancy. Diagnosing Cushing's syndrome during a pregnancy is complex because the biochemical features are obscured by the natural changes in the hypothalamic-pituitary-adrenal axis that occur during pregnancy. Having Cushing's syndrome during a pregnancy results in increased fetal and maternal complications, so early diagnosis and treatment are critical. We report the clinical and endocrine findings of a pregnant women with Cushing's disease who underwent transsphenoidal surgery after delivery.

Comparison of Vildagliptin-Metformin and Glimepiride-Metformin Treatments in Type 2 Diabetic Patients

BACKGROUND: The present study investigated the efficacy and safety of vildagliptin-metformin treatment compared to those of glimepiride-metformin treatment for type 2 diabetes. METHODS: In a randomized, open-label, comparative study, 106 patients with type 2 diabetes were enrolled. The primary endpoint was a reduction in HbA1c from baseline and secondary endpoints included fasting plasma glucose (FPG) or 2-hour postprandial glucose (2h-PPG) reduction from baseline, as well as HbA1c responder rate and HbA1c reduction according to baseline HbA1c category. RESULTS: Comparable HbA1c reduction was observed with a mean+/-standard deviation change from baseline to the 32-week endpoint of -0.94+/-1.15% in the vildagliptin group and -1.00+/-1.32% in the glimepiride group. A similar reduction in 2h-PPG (vildagliptin group 3.53+/-4.11 mmol/L vs. the glimepiride group 3.72+/-4.17 mmol/L) was demonstrated, and the decrements in FPG (vildagliptin group 1.54+/-2.41 mmol/L vs. glimepiride group 2.16+/-2.51 mmol/L) were not different between groups. The proportion of patients who achieved an HbA1c less than 7% at week 32 was 50.1% in the vildagliptin group and 56.0% in the glimepiride group. An average body weight gain of 2.53+/-1.21 kg in the glimepiride group was observed in contrast with the 0.23+/-0.69 kg weight gain noted in the vildagliptin group. A 10-fold lower incidence of hypoglycemia was demonstrated in the vildagliptin group, in addition to an absence of severe hypoglycemia. CONCLUSION: Vildagliptin-metformin treatment provided blood glucose control efficacy comparable to that of glimepiride-metformin treatment and resulted in better adverse event profiles with lower risks of hypoglycemia and weight gain.

CellprepPlus(R) Liquid-based Smear in Sono-guided Thyroid Fine Needle Aspiration: A Comparison of Conventional Method and CellprepPlus(R) Liquid-based Cytology

BACKGROUND: Fine needle aspiration (FNA) of the thyroid is a useful tool for the evaluation of benign or malignant thyroid nodules. The improvements in the quality of cytological preparations using the liquid-based cytology (LBC) method have been well-documented. The principal objective of this study was designed to evaluate the diagnostic adequacy, sensitivity, and specificity of the thyroid FNA comparing a conventional smear with the LBC adapted with the filtration method described herein. METHODS: One hundred ninety eight cases of FNA samples obtained from May 2009 to September 2009 were included in this study. All patients were subjected to ultrasound-guided aspiration twice at a target lesion by a radiologist and two types of slides were prepared using conventional smear and LBC. RESULTS: When compared with conventional method, the cellularity was reduced in LBC. However, the malignant tumor cells evidenced the larger and more vesicular nuclei, prominent nucleoli, and distinct nuclear membranes in LBC. Thirty two cases (16.16%) of conventional smear were inadequate, but 96 cases (48.49%) of LBC were inadequate. CONCLUSIONS: Most of the slides using CellprepPlus(R) LBC evidenced lower cellularity and clearer background. However, the conventional smears were found to generate much more applicable samples than CellprepPlus(R) LBC.

Delivery of Factor VIII Gene into Skeletal Muscle Cells Using Lentiviral Vector

PURPOSE: This study was designed to investigate whether transduction of lentiviral vectors (LV) carrying human coagulation factor VIII (hFVIII) cDNA into skeletal muscle could increase circulating hFVIII concentrations. MATERIALS AND METHODS: A LV containing bacterial LacZ gene as a control or human FVIII gene was intramuscularly administered into the thigh muscle of 5 weeks old Sparague-Dawley rats. The plasma human FVIII concentration and neutralizing anti-FVIII antibodies were measured for up to 12 weeks in these experimental animals. RESULTS: The plasma human FVIII levels in the rats injected with LV carrying FVIII cDNA peaked at post-injection 1st week (5.19 +/- 0.14 ng/mL vs. 0.21 +/- 0.05 ng/mL in control rats , p < 0.05). Elevated hFVIII concentrations were maintained for 4 weeks (2.52 +/- 0.83 ng/mL vs. 0.17 +/- 0.08 ng/mL in control rats, p < 0.05) after a single intramuscular injection. In the Bethesda assay, neutralizing antibodies for FVIII protein were detected only in FVIII-LV injected rats by the 10th week, but not in control rats. CONCLUSION: This study suggested that a single administration of an advanced generation LV carrying the human FVIII cDNA resulted in elevation of FVIII level in immune competent rats, and that this gene transfer approach to the skeletal muscle could be an effective tool in treatment of hemophilia A.

Association Study of the Peroxisome Proliferators-Activated Receptor gamma2 Pro12Ala Polymorphism with Diabetic Nephropathy / 당뇨병

BACKGROUND: Peroxisome proliferators-activated receptor gamma (PPARgamma) is a member of the nuclear hormone receptor superfamily of ligand-activated transcription factors and known to play a role in regulating the expression of numerous genes involved in lipid metabolism, metabolic syndrome, inflammation, and atherosclerosis. The PPARgamma2 Pro12Ala polymorphism has recently been shown to be associated with diabetic nephropathy. In this study, we evaluated the relationship between PPARgamma2 Pro12Ala polymorphism and type 2 diabetic nephropathy whose duration of diabetes was over 10 years. METHODS: We conducted a case-control study, which enrolled 367 patients with type 2 diabetes. Genotyping of PPARgamma2 Pro12Ala polymorphism was performed using polymerase chain reaction followed by digestion with Hae III restriction enzyme. RESULTS: The genotype or allele frequencies of PPARgamma2 Pro12Ala polymorphism were not significantly different in diabetic patients with or without diabetic nephropathy. The genotype frequencies in terms of diabetic retinopathy and macrovascular complications such as coronary artery disease or stroke were not different either. Interestingly, nephropathy patients with Ala/Pro genotype showed lower C-peptide levels than those of Pro/Pro genotype. CONCLUSION: Our results suggest that PPARgamma2 Pro12Ala polymorphism is not associated with diabetic nephropathy in type 2 diabetic patients.