Effects of Ranibizumab, Bevacizumab, and Aflibercept on Senescent Retinal Pigment Epithelial Cells

PURPOSE: Anti-vascular endothelial growth factor (VEGF) agents have been used for the last 10 years, but their safety profile, including cytotoxicity against various ocular cells such as retinal pigment epithelial (RPE) cells, remains a serious concern. Safety studies of VEGF agents conducted to date have primarily relied on healthy RPE cells. In this study, we assessed the safety of three anti-VEGF agents, namely, ranibizumab, bevacizumab, and aflibercept, on senescent RPE cells. METHODS: Senescent human induced pluripotent stem cell-derived RPE cells were generated by continuous replication and confirmed with senescence biomarkers. The viability, proliferation, protein expression, and phagocytosis of the senescent RPE cells were characterized 3 days after anti-VEGF treatment with clinical doses of ranibizumab, bevacizumab, or aflibercept. RESULTS: Clinical doses of ranibizumab, bevacizumab, or aflibercept did not decrease the viability or alter proliferation of senescent RPE cells. In addition, the anti-VEGF agents did not induce additional senescence, impair the protein expression of zonula occludens-1 and RPE65, or reduce the phagocytosis capacity of senescent RPE cells. CONCLUSIONS: Clinical dosages of ranibizumab, bevacizumab, or aflibercept do not induce significant cytotoxicity in senescent RPE cells.

Reduction of Sulfonylurea with the Initiation of Basal Insulin in Patients with Inadequately Controlled Type 2 Diabetes Mellitus Undergoing Long-Term Sulfonylurea-Based Treatment

BACKGROUND: There were a limited number of studies about β-cell function after insulin initiation in patients exposed to long durations of sulfonylurea treatment. In this study, we aimed to evaluate the recovery of β-cell function and the efficacy of concurrent sulfonylurea use after the start of long-acting insulin. METHODS: In this randomized controlled study, patients with type 2 diabetes mellitus (T2DM), receiving sulfonylurea for at least 2 years with glycosylated hemoglobin (HbA1c) >7%, were randomly assigned to two groups: sulfonylurea maintenance (SM) and sulfonylurea reduction (SR). Following a 75-g oral glucose tolerance test (OGTT), we administered long-acting basal insulin to the two groups. After a 6-month follow-up, we repeated the OGTT. RESULTS: Among 69 enrolled patients, 57 completed the study and were analyzed: 31 in the SM and 26 in the SR group. At baseline, there was no significant difference except for the longer duration of diabetes and lower triglycerides in the SR group. After 6 months, the HbA1c was similarly reduced in both groups, but there was little difference in the insulin dose. In addition, insulin secretion during OGTT was significantly increased by 20% to 30% in both groups. A significant weight gain was observed in the SM group only. The insulinogenic index was more significantly improved in the SR group. CONCLUSION: Long-acting basal insulin replacement could improve the glycemic status and restore β-cell function in the T2DM patients undergoing sulfonylurea-based treatment, irrespective of the sulfonylurea dose reduction. The dose reduction of the concurrent sulfonylurea might be beneficial with regard to weight grain.

Comparison of Biometric Measurements and Refractive Results between Applanation Ultrasonography and Three Different Interferometries

PURPOSE: To compare ocular biometry and refractive results measured using conventional applanation ultrasonography and 3 different optical interferometries, Lenstar LS900(R), AL-Scan(R) and OA-2000(R). METHODS: The biometries of 31 cataractous eyes were measured using ultrasonography, Lenstar LS900(R), AL-Scan(R) or OA-2000(R). The axial length, anterior chamber depth and keratometry were measured. The SRK/T formula was used to calculate intraocular lens power. Two months after cataract surgery, the refractive outcome was determined and results from the 4 different biometry methods were compared. RESULTS: Axial lengths were 23.39 +/- 0.95 mm, 23.42 +/- 0.98 mm, 23.43 +/- 0.98 mm and 23.44 +/- 0.98 mm measured using ultrasonography, Lenstar LS900(R), AL-Scan(R) and OA-2000(R), respectively with no statistically significant differences observed (p = 0.996). The anterior chamber depth and keratometry were 3.14 +/- 0.41 mm, 3.10 +/- 0.38 mm and 3.13 +/- 0.39 mm (p = 0.936) and 44.41 +/- 1.52 D, 44.54 +/- 1.57 D and 44.44 +/- 1.52 D (p = 0.937) for Lenstar LS900(R), AL-Scan(R) and OA-2000(R) respectively. There were no statistically significant differences between the 3 optical devices. The mean absolute error of the 4 different devices were not statistically significant (p = 0.722). CONCLUSIONS: The ocular biometric measurements and prediction of postoperative refraction using ultrasonography, Lenstar LS900(R), AL-Scan(R) or OA-2000(R) showed no significant differences.

The Insulin Resistance but Not the Insulin Secretion Parameters Have Changed in the Korean Population during the Last Decade

BACKGROUND: This study aimed to compare the patterns of insulin secretion and resistance between Korean subjects in the 1990s and 2000s. METHODS: Insulin secretion and resistance indices were calculated from subjects who underwent 75-g oral glucose tolerance tests in the year 1997 to 1999 and 2007 to 2011 at the Seoul St. Mary's Hospital, Korea. RESULTS: A total of 578 subjects from the 1990s (mean age, 48.5 years) and 504 subjects from the 2000s (mean age, 50.2 years) were enrolled. Compared with the subjects from the 1990s, those from the 2000s exhibited increased insulin resistance (increased homeostatic model assessment for insulin resistance), and reduced insulin sensitivity (reduced Matsuda index and quantitative insulin sensitivity check index), regardless of their glucose tolerance status. However, insulinogenic index did not reveal significant differences between the 2 decades in subjects with or without diabetes. A distinct relationship was confirmed between Matsuda index and total area under the curve (insulin/glucose) in each glucose tolerance group. The mean product of the Matsuda index and the total area under the curve (insulin/glucose) as well as the oral disposition index, was lower in subjects with normal glucose tolerance from the 2000s than in those from the 1990s. CONCLUSION: After rapid economic growth and changes in lifestyle patterns, insulin resistance has worsened across the glucose tolerance status; however, the insulin secretory function remained unchanged, which resulted in an increase in the susceptibility to the development of type 2 diabetes mellitus among Korean subjects without diabetes. We could not rule out the potential selection bias and therefore, further studies in general Korean population are needed.

A Case of Pigmented Free-Floating Posterior Vitreous Cyst

PURPOSE: To report a case of a 59-year-old female with a free-floating monolateral vitreous cyst localized in the posterior vitreous in the left eye. CASE SUMMARY: A 59-year-old female who complained of an intermittent floater in the left eye for 3 months visited our clinic. She had been suffering from visual disturbance for approximately 3 months. There was no previous history of trauma, infection, or inflammatory disorders. The best corrected visual acuity was 20/20 in both eyes. On fundoscopic exam, a 3-4 disc diameter (DD) sized, brown-colored pigmented vitreous cyst was detected at the inferior temporal side of the posterior vitreous in her left eye. B-scan ultrasound confirmed the presence of an echo-free cystic formation that was free from surrounding vitreous strands or other adhesions located at the posterior vitreous. No specific findings or leakage were observed on fluorescein angiography. We followed-up the patient periodically (1 month, 3 months, and 6 months after the initial visit) and monitored whether the size or location of the cyst had changed. At every follow-up exam, the size or location of the cyst was stationary and the patient's visual acuity was 20/20 in the affected eye, thus we suggested she should be followed-up periodically for her cyst without any intervention. CONCLUSIONS: We report a case of a patient with no previous ocular history or impaired vision who had a free-floating vitreous cyst localized in the posterior vitreous in the left eye. The disease did not appear to progress or become aggravated over a short-term follow-up period and no specific treatment was required.

Refractive Eerror According to the Anterior Chamber Depth and Corneal Refractive Power in Short Eyes

PURPOSE: To evaluate the accuracy of the chosen formula in short eyes and the effect of the anterior chamber depth (ACD) and corneal refractive power on the accuracy. METHODS: A total of 251 eyes out of 185 patients (axial length below 22.0 mm) who underwent cataract surgery in our hospital were retrospectively studied. Introcular lens (IOL) power was calculated with the Hoffer Q, SRK II, SRK-T and Holladay 1 formulas and refractive outcome was measured. Patients were divided into 2 groups based on ACD. The accuracy of the 4 formulas was compared and the errors according to the ACD were also evaluated. RESULTS: In eyes with short axial lengths, all formulas showed a tendency for hyperopic shifts. The Hoffer Q formula showed significantly high predictive accuracy. This tendency for hyperopic shifts was similar in the eyes with extremely short axial length, but a large refractive error deviation was observed. The 2 groups based on ACD showed no significant difference in the refractive error, but the group with deep ACD had a tendency for hyperopic shifts. The difference of the calculated IOL power between the 4 formulas was more pronounced in eyes with lower corneal refractive power. CONCLUSIONS: In eyes with short axial lengths, preoperative ACD and corneal refractive power had an influence on the accuracies of predicted IOL power. Therefore, these factors should be considered in IOL power determination.

Predictive Clinical Parameters and Glycemic Efficacy of Vildagliptin Treatment in Korean Subjects with Type 2 Diabetes

BACKGROUND: The aims of this study are to investigate the glycemic efficacy and predictive parameters of vildagliptin therapy in Korean subjects with type 2 diabetes. METHODS: In this retrospective study, we retrieved data for subjects who were on twice-daily 50 mg vildagliptin for at least 6 months, and classified the subjects into five treatment groups. In three of the groups, we added vildagliptin to their existing medication regimen; in the other two groups, we replaced one of their existing medications with vildagliptin. We then analyzed the changes in glucose parameters and clinical characteristics. RESULTS: Ultimately, 327 subjects were analyzed in this study. Vildagliptin significantly improved hemoglobin A1c (HbA1c) levels over 6 months. The changes in HbA1c levels (DeltaHbA1c) at month 6 were -2.24% (P=0.000), -0.77% (P=0.000), -0.80% (P=0.001), -0.61% (P=0.000), and -0.34% (P=0.025) for groups 1, 2, 3, 4, and 5, respectively, with significance. We also found significant decrements in fasting plasma glucose levels in groups 1, 2, 3, and 4 (P<0.05). Of the variables, initial HbA1c levels (P=0.032) and history of sulfonylurea use (P=0.026) were independently associated with responsiveness to vildagliptin treatment. CONCLUSION: Vildagliptin was effective when it was used in subjects with poor glycemic control. It controlled fasting plasma glucose levels as well as sulfonylurea treatment in Korean type 2 diabetic subjects.

Comparison of the Efficacy of Glimepiride, Metformin, and Rosiglitazone Monotherapy in Korean Drug-Naive Type 2 Diabetic Patients: The Practical Evidence of Antidiabetic Monotherapy Study

BACKGROUND: Although many anti-diabetic drugs have been used to control hyperglycemia for decades, the efficacy of commonly-used oral glucose-lowering agents in Korean type 2 diabetic patients has yet to be clearly demonstrated. METHODS: We evaluated the efficacy of glimepiride, metformin, and rosiglitazone as initial treatment for drug-naive type 2 diabetes mellitus patients in a 48-week, double-blind, randomized controlled study that included 349 Korean patients. Our primary goal was to determine the change in HbA1c levels from baseline to end point. Our secondary goal was to evaluate changes in fasting plasma glucose (FPG) levels, body weight, frequency of adverse events, and the proportion of participants achieving target HbA1c levels. RESULTS: HbA1c levels decreased from 7.8% to 6.9% in the glimepiride group (P<0.001), from 7.9% to 7.0% in the metformin group (P<0.001), and from 7.8% to 7.0% (P<0.001) in the rosiglitazone group. Glimepiride and rosiglitazone significantly increased body weight and metformin reduced body weight during the study period. Symptomatic hypoglycemia was more frequent in the glimepiride group and diarrhea was more frequent in the metformin group. CONCLUSION: The efficacy of glimepiride, metformin, and rosiglitazone as antidiabetic monotherapies in drug-naive Korean type 2 diabetic patients was similar in the three groups, with no statistical difference. This study is the first randomized controlled trial to evaluate the efficacy of commonly-used oral hypoglycemic agents in Korean type 2 diabetic patients. An additional subgroup analysis is recommended to obtain more detailed information.

The Effect of Parental Transmission of Diabetes on the Development of Gestational Diabetes Mellitus

No abstract available.

Erratum: The usefulness of ischemia modified albumin as an early ischemic marker to detect coronary artery disease in patients with chest pain presenting to the emergency department / 대한내과학회지

No abstract available.

The usefulness of ischemia modified albumin as an early ischemic marker to detect coronary artery disease in patients with chest pain presenting to the emergency department / 대한내과학회지

BACKGROUND: A diagnosis of coronary artery disease (CAD) in the early phase of acute chest pain is often difficult in an emergency department (ED) due to the lower sensitive ECG and delayed expression of the cardiac necrosis markers. Ischemia modified albumin (IMA) has recently been reported to be an early sensitive biochemical marker of ischemia. The aim of this study was to evaluate the diagnostic value of IMA in patients with suspected CAD and less sensitive ECG/delayed cardiac necrosis markers. METHODS: 100 consecutive patients (mean age: 5413 years, male: 66%) presenting to the ED with suspected CAD and chest pain within 6 hours of chest pain were enrolled in this study. An ECG check and blood sampling for IMA and CK-MB, cardiac troponin-T (TnT) were done within 1 hour at the ED. The diagnosis of CAD was based upon the clinical findings, results of serial ECG/TnT and coronary angiography. The ideal cutoff value of IMA for CAD was calculated by the Receiver Operator Characteristic (ROC) curve analysis. RESULTS: CAD including acute coronary syndrome was diagnosed in 69/100 (69%). The optimum diagnostic cutoff point for the IMA levels in these study populations was found by ROC analysis to be 99.5 U/mL. The ROC curve area for the IMA test was 0.901 (95% confidential interval, 0.840-0.961, p=0.001). The IMA levels >99.5 U/mL demonstrated a sensitivity of 86%, specificity of 81%, positive predictive value of 90% and negative predictive value of 74% for the diagnosis of CAD. The combination of IMA-ECG-CKMB/TnT increased the sensitivity for detecting ischemia to 94%, with a negative predictive value of 85%. IMA is a highly sensitive with a high negative predictive value, and might improve the utility of standard biomarkers for CAD. CONCLUSIONS: IMA might be a useful ischemic marker of coronary artery disease in patients presenting within 6 hours after the onset of chest pain.

A Case of Rectal Gastrointestinal Stromal Tumor with Bleeding / 대한소화기내시경학회지

Gastrointestinal stromal tumors (GIST), although uncommon mesenchymal tumors of the gastrointestinal tract, are occasionally encountered on endoscopic examination. GIST can be found all gastrointestinal tract, but rare in the rectum. We report a 72-year-old woman presented with intermittent bloody stool for a year. On rectal examination, a firm fixed mass was felt on the anterior wall of the rectum. Computed tomography revealed the 4.8x4.5 cm sized exophytic and centrally depressed mass on the rectum without the evidence of adjacent organ invasion or metastasis. On colonoscopic examination, there was a round elevated lesion having central ulcer with adherent blood clots. Endoscopic deep biopsy examination revealed a submucosal tumor consisting of spindle cells with elongated cigar-shaped nuclei arranged in fascicles and whorls. Mitotic counts were fewer than 5 per 50 high-power fields. The tumor cells were positive for KIT and CD34 immunohistostaining and negative for SMA. Local excision recommended, but the patient discharged against the advice.

Clinical Analysis Of Iga Nephropathy In Patients Over 50 Years Of Age / 대한내과학회지

BACKGROUND: IgA nephropathy is recognized as a disease affecting primarily young men under 30 years of age but it is relatively uncommon over 50 years of age. Findings on clinical and histological presentation and outcome of over 50 years of age have rarely published in Korea. METHODS: Between Febrary 1994 and July 2003, one hundred and thirty nine IgAN patients were recruited over 8 years. Nineteen patients over age 50 were compared to one hundred and twenty patients under age 50 clinical, histological findings, 5-Yr renal survival rate. Mean post-biopsy follow-up month was 23.8 +/- 23.5 months. RESULTS: Both group of patients were similar to baseline for gross hematuria, Male and female ratio. But older patients had a higher incidence of daily for 24 hour urine protein (p=0.010), systolic and diastolic blood pressure (p=0.010, p<0.01), serum C3 (p=0.001) and serum C4 (p=0.003). Albumin (p=0.011), creatinine clearance (p<0.01) were significantly lower in the older patients at the time of renal biopsy. Histologic grade IV was more common in the older patients (p=0.001). Moderate to severe mesangial proliferation (p=0.001) and crescent formation (p=0.043), arteriolosclerosis (p=0.006) were more common in older patients. Mesangial small deposition of IgA (p=0.007) and glomerular peripheral deposition of IgG, IgA, C1q (p=0.024, p=0.014, p=0.009) were more common in older patients than in under 50 years of age. Mesangial small electron dense deposits were more common in older patients than in younger patients (p=0.031). CRF (Ccr < 60 mL/min) was confirmed 55.6% over age 50 and 27.4% under age 50 (p=0.017). Renal replacement therapy was done 15.8% over age 50 and 4.3% under age 50 (p=0.048). 5-Year renal survival curves showed that kidney survival rate was 44.4% over age 50 and 72.6% under age 50 (p=0.0248). CONCLUSION: Poor prognostic factors were more common over age 50 than under age 50. CRF and renal replacement therapy were more common over age 50. Analysis of renal survival curves shows that the probability of developing ESRF increase after age 50. But, prolonged prospective follow-up is necessary to confirm this trend.

A case of minimal change nephropathy with malignant thymoma / 대한내과학회지

It is the first case that nephrotic syndrome with malignant thymoma reported in Korea. A 56-year-old man have had generalized edema, weight gain, dyspnea, oliguria for 10 days. At that time, a full blown nephrotic syndrome developed, with minimal change glomerulopathy, A mediastinum mass was shown by the chest X-ray. Thymectomy and palliative radiotherapy was done. In the treatment of nephrotic syndrome, firstly diuretics and prednisolone were given. but the response was poor, so additionally cyclophosphamide and azathioprine were given. After 1 year passed, the patient died of the respiratory failure with pulmonary fibrosis of complication of radiotherapy, without improvement in nephrotic syndrome.

Effect of Office-Based Patient Education for Fat Distribution and Behavior Modification in Overweight Patients

BACKGROUND: It is generally known that the principle treatment of obesity is life-style modification and behavior therapy for weight reduction. This study was carried out to investigate the effect of office-based education for weight control and behavior modification in overweight patients. METHODS: We selected 119 patients among the overweight or obese (BMI >or=23 kg/m2) patients who visited the Department of Family Medicine at Asan Medical Center. Life styles such as diet, exercise, smoking, and alcohol drinking were evaluated by self-questionnaire. Weight, height, body mass index, waist circumference, waist to hip ratio, and body fat were measured. The patients were divided randomly into two groups, the intervention (n=60) and the control (n=59) group. We educated the intervention group about the importance of weight reduction, life-style modification and provided specific guidelines. Two months later, we measured anthropometric variables and evaluated changes of behavior modification. RESULTS: After two months, 28 patients of the intervention group and 22 patients of the control group were followed up. At the follow-up time, the body weight and waist circumference decreased significantly in the intervention group compared with those of the control group. The exercise time increased significantly in the intervention group compared to the control group. The frequency of fatty meal ingestion decreased significantly in the intervention group. CONCLUSIONS: The office-based education for weight reduction in overweight or obese patients has contributed substantially in changing their life-style and reducing their waist circumference. As a result, we have found that patient education for behavior modification was essential part of comprehensive approach for weight control in overweight patients.

Psychosocial Factors and Familial Environments in Adolescent Obesity

BACKGROUND: Adolescent obesity has a high risk of developing into adult obesity and may cause many physical and psychological problems. The purpose of this study was to investigate familial environment and psychosocial factors of adolescent obesity. METHODS: A total of 1,153 students from one middle school located in suburban area were chosen as subjects. In this study, the obese group was defined to have an obesity index higher than 85 pecentile, compared to the normal weight group which ranged between 25 and 75 percentile. The questionnaires included items on familial environment and psychosocial factors, their parents' BMI, physical activity, self esteem inventory, depression self rating scale, and FACES III (family cohesion and adaptability scale III). RESULTS: Maternal BMI of the obese group was significantly higher than that of the normal weight group. The mean self esteem score of the obese group was significantly lower than that of the normal weight group. Depression self-rating score of the female obese group was significantly higher than that of the normal weight group. There was no difference in family functioning between the obese group and the normal weight group. CONCLUSION: In multivariate analysis, there were significant correlations among adolescent obesity and higher maternal BMI and lower self-esteem. It will be necessary to evaluate and support the psychosocial factors in the management of adolescent obesity.

The Difference in Graft Rejection between Two Corneal Preservation Methods(Moist Chamber vs Optisol)

To know the difference in graft rejection after corneal transplantation between moist chamber and Optisol(Chiron Co. Irvine, CA, U.S.A.) as cornea preservation methods, we compared two groups involving 50 patients(71 eyes) who had undergone partially penetrating keratoplasty (PPKP) for the treatment of keratoconus or corneal dystrophy from 1991 to 1995. The graft rejection had occurred in 10 of 40 eyes(25%) in moist chamber group and 9 of 31 eyes(29%) in Optisol group, and the cases of permanent corneal opacity after rejection were 5 of 40 eyes(12.5%), 3 of 31 eyes(9.7%) respectively. No difference in the two groups was statistically significant(P<0.05). We found the fact that the difference did not exist in the results from graft rejection after PPKP using moist chamber method for short preservation period, or Optisol method for the relatively long period allowing serological and immunological screen test.

Clinical Analysis of Uveitis by the Diagnostic Studies

In order to investigate the efficiency of various laboratory studies of uveitis, we performed a series of studies including complete boold count, immunologic tests and radiolgic examination for 70 patients with uveitis and same number of controls who had visited at St. Mary's Hospital, Catholic University Medical College from October 1992 to May 1993. The series of uveitis consists of 24 patients(34.3%) of anterior uveitis, 20 patients(28.6%) of posterior uneitis and 17 patients(24.3%) of intermediate uveitis. Only 7 cases presented positive results for the specific laboratory studies. Two patients of uveitis were positive for cytomegalovirus IgM, one for toxoplasma IgG and one for VDRL. One patient showed evidence of sacroilitis on sacroiliac joint X-ray. Skin test for Clonorchis sinensis was positive in one patient of uveitis. One case in the control group was positive for toxoplasma IgG. From the above results, we suggest that the selective laboratory studies should be carried out on the basis of the patient's histories and ocular findings for the more specific and etiological diagnosis of uveitis.

Three Cases of Binocular Dipolpia Presenting after Cataract Surgery

Binocular diplopia after catarat surgery is a rare phenomenon, and it happens by variable mechanisms including extraocular muscle injury during bridle suture placement and myotoxicity of local anesthetics. We experienced three cases of binocular diplopia following successful cataract surgery in patients who had no history of strabismus, amblyopia and neurologic or systemic disease which might be related to mobility disorder. We report these cases and previous literature is reviewed.

A Case of Radiotheraphy of Choroidal Metastasis of Breast Carcinoma

Ocular metastasis of metastatic carcinoma is the most common intraocular malignancy. The most common pr1mary Site of the lntraocular metastatic tumor is the breast ln women and the lung 1n men respectlvely and the choroid Is by far the most common site for intraocular metastasis. RadlOtherapy has been reported hlghly effect1ve in pal1iative treatment for metastatic tumor. We experienced a case choroidal metastasis in a known metastatic breast carcinoma patient and gained clinical lmprovement by rad1otherapy in this case.