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Background@#Voriconazole, a triazole antifungal agent exhibits broad-spectrum antifungal activity. It is used to treat severe, invasive fungal infections, including invasive aspergillosis and candidemia. The aim of this study was to assess the pharmacokinetic equivalence of a test formulation (Vorico® Injection) and reference formulation (Vfend® IV) of voriconazole. @*Materials and Methods@#This was a randomized, open-label, single-dose, three-group, two-treatment, two-sequence, two-period, crossover phase I trial with 7-day washout periods (ClinicalTrials.gov identifier NCT02631954). Twenty-four healthy Korean male subjects were recruited. In each group, eight subjects were randomized in a 1:1 manner to receive a single dose of 200 mg test or reference formulation intravenously over 1.5 h. Blood samples were collected over 24 h post-dose, and plasma drug concentrations were determined by liquid chromatography-tandem mass spectrometry. Pharmacokinetic parameters were determined using a non-compartmental analysis, and safety was evaluated. @*Results@#Twenty-three subjects completed the study. The geometric mean ratio (90% confidence interval) of the test formulation to reference formulation was 0.9570 (0.8178 – 1.1199) for the maximum plasma concentration (Cmax) and 1.0720 (1.0262 – 1.1198) for the area under the concentration–time curve from dosing to the last quantifiable concentration (AUClast). The mean plasma concentration–time profiles, pharmacokinetic parameters, and safety were comparable between the two formulations. @*Conclusion@#Equivalent pharmacokinetic characteristics that satisfied the criteria of bioequivalence and similar safety profiles were observed for both test and reference formulations of voriconazole.
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BACKGROUND: The aim of the study was to assess the impact of socioeconomic status (SES) on health behaviors, metabolic control, and chronic complications in people with type 2 diabetes mellitus (T2DM) from South Korea, a country with universal health insurance coverage and that has experienced rapid economic and social transition. METHODS: A total of 3,294 Korean men and women with T2DM aged 30 to 65 years, participating in the Korean National Diabetes Program (KNDP) cohort who reported their SES and had baseline clinical evaluation were included in the current cross-sectional analysis. SES included the level of education and monthly household income. RESULTS: Lower education level and lower income level were closely related, and both were associated with older age in men and women. Women and men with lower income and education level had higher carbohydrate and lower fat intake. After adjustment for possible confounding factors, higher education in men significantly lowered the odds of having uncontrolled hyperglycemia (glycosylated hemoglobin ≥7.5%) (odds ratio [OR], 0.63; 95% confidence interval [CI], 0.43 to 0.91 for highest education; P(trend)=0.048), while higher household income in men significantly lowered the odds of having diabetic retinopathy (OR, 0.59; 95% CI, 0.37 to 0.95 for highest income level; P(trend)=0.048). In women, lower income was associated with a higher stress level. CONCLUSION: Men with lower SES had higher odds of having diabetic retinopathy and uncontrolled hyperglycemia, showing the need to improve care targeted to this population.
Subject(s)
Female , Humans , Male , Cohort Studies , Cross-Sectional Studies , Diabetes Mellitus, Type 2 , Diabetic Retinopathy , Education , Family Characteristics , Health Behavior , Hyperglycemia , Insurance, Health , Korea , Social ClassABSTRACT
Chemerin is a recently identified adipokine suggested to play a role in obesity and its metabolic complications. The relationship between visceral obesity and serum chemerin levels in type 2 diabetes (T2DM) is unknown and may differ from that of subjects without diabetes. Therefore, we evaluated whether serum chemerin was associated with visceral abdominal obesity in patients with T2DM. A total of 218 Korean patients with T2DM were enrolled and metabolic parameters, abdominal visceral and subcutaneous fat areas, and serum chemerin levels were measured. Serum chemerin level showed positive correlation with fasting insulin, HOMA-IR, serum triglyceride, serum creatinine, urine albumin/creatinine ratio, high-sensitivity C-reactive protein (hsCRP), fibrinogen, abdominal visceral fat area, visceral to subcutaneous fat area ratio, and negatively correlation with high density lipoprotein cholesterol and creatinine clearance (CCr) after adjusting for age, gender and body mass index. Multiple linear stepwise regression analysis showed that abdominal visceral fat area (β = 0.001, P < 0.001), serum triglyceride (β = 0.001, P < 0.001), CCr (β = -0.003, P = 0.001), hsCRP (β = 0.157, P = 0.001), fibrinogen (β = 0.001, P < 0.001) and BMI (β = 0.02, P = 0.008) independently affected log transformed serum chemerin levels. Higher serum chemerin level was associated with higher level of abdominal visceral fat area, serum triglyceride, hsCRP and fibrinogen and lower level of CCr in patients with T2DM. Serum chemerin may be used as a biomarker of visceral adiposity and chemerin may play a role in inflammation, decreased renal function, and increased cardiovascular risk in T2DM.
Subject(s)
Adult , Female , Humans , Male , Middle Aged , Biomarkers/blood , Body Mass Index , C-Reactive Protein/analysis , Chemokines/blood , Creatinine/blood , Diabetes Mellitus, Type 2/blood , Insulin/blood , Intercellular Signaling Peptides and Proteins/blood , Intra-Abdominal Fat/pathology , Linear Models , Lipocalins/blood , Obesity/complications , Triglycerides/bloodABSTRACT
BACKGROUND: Metformin is considered the first choice oral treatment for type 2 diabetes patients in the absence of contraindications. Rarely, life-threatening complications associated with metformin treatment are seen in some patients with underlying diseases. The aim of this study was to further investigate the clinical profiles and risk factors for metformin-associated lactic acidosis (MALA) and the treatment modalities according to survival. METHODS: To identify MALA, we performed a retrospective study in seven diabetic patients who were taking metformin and had been diagnosed with lactic acidosis at Inha University Hospital between 1995 and 2012. For each patient, we recorded the age, sex, daily metformin dosage, laboratory test results, admission diagnosis, and risk factors. Also, concurrent conditions, treatment modalities, and outcomes were evaluated. RESULTS: Six patients had risk factors for lactic acidosis before admission. All patients had renal impairment on admission as a precipitating risk factor. Five patients survived and two patients died despite early renal replacement therapy. Older patients tended to have a poorer prognosis. CONCLUSION: Renal function must be monitored in elderly type 2 diabetes mellitus patients with underlying diseases and conditions causing renal impairment who begin metformin treatment. Accurate recognition of MALA and initiation of renal replacement are essential for treatment.
Subject(s)
Aged , Humans , Acidosis, Lactic , Causality , Diabetes Mellitus, Type 2 , Diagnosis , Metformin , Prognosis , Renal Replacement Therapy , Retrospective Studies , Risk FactorsABSTRACT
Gestational diabetes mellitus (GDM) is a strong predictor of postpartum prediabetes and transition to overt type 2 diabetes (T2DM). Although many reports indicate that low magnesium is correlated with deteriorated glucose tolerance, the association between postpartum serum magnesium level and the risk for T2DM in women with a history of GDM has not been evaluated. We analyzed postpartum serum magnesium levels and development of prediabetes and T2DM in women with prior GDM according to American Diabetes Association (ADA) criteria using the Korean National Diabetes Program (KNDP) GDM cohort. During a mean follow-up of 15.6+/-2.0 months after screening, 116 women were divided into three groups according to glucose tolerance status. Ultimately, eight patients (6.9%) were diagnosed with T2DM, 59 patients (50.9%) with prediabetes, and 49 patients (42.2%) with normal glucose tolerance (NGT) after follow-up. The T2DM group had the lowest serum magnesium level (0.65 [0.63-0.68] mM/L) in the postpartum period, but there was no significant difference between the prediabetes group (0.70 [0.65-0.70] mM/L) and the NGT group (0.70 [0.65-0.70] mM/L) (P=0.073) Multiple logistic regression analysis showed that postpartum HOMA-IR was a significant predictor of both prediabetes and T2DM. Moreover, we found that postpartum serum magnesium level was also a possible predictor for T2DM development. Serum magnesium level in the postpartum period may be a possible predictor for T2DM development in women with a history of GDM.
Subject(s)
Adult , Female , Humans , Pregnancy , Blood Glucose , Cohort Studies , Diabetes Mellitus, Type 2/blood , Diabetes, Gestational/blood , Glucose Intolerance/blood , Glucose Tolerance Test , Insulin Resistance , Magnesium/blood , Postpartum Period/blood , Prediabetic State/diagnosis , Prospective Studies , Republic of Korea , Risk FactorsABSTRACT
BACKGROUND: The Korean National Diabetes Program (KNDP) cohort study is performing an ongoing large-scale prospective multicenter investigation to discover the pathogenesis of type 2 diabetes in Korean patients. This study was performed to examine the prevalence of chronic complications in patients with type 2 diabetes among those registered in the KNDP cohort within the past 4 years. METHODS: This study was performed between June 2006 and September 2009 at 13 university hospitals and included 4,265 KNDP cohort participants. Among the participants, the crude prevalence of microvascular and macrovascular diseases of those checked for diabetes-related complications was determined, and the adjusted standard prevalence and standardization of the general population prevalence ratio (SPR) was estimated based on the 2005 Korean National Health and Nutrition Examination Survey (KNHANES) population demographics. RESULTS: Among the KNDP registrants, 43.2% had hypertension, 34.8% had dyslipidemia, 10.8% had macrovascular disease, and 16.7% had microvascular disease. The SPR of the KNDP registrants was significantly higher than that of the KNHANES subjects after adjusting for demographics in the KNHANES 2005 population. However, with the exception of cardiovascular disease in females, the standardized prevalence for the most complicated items in the survey was significantly higher than that in the KNHANES subjects. CONCLUSION: The prevalence of macrovascular disease and peripheral vascular disease were significantly higher in Korean patients with type 2 diabetes than in the normal population. However, no significant difference was noted in the prevalence of cardiovascular disease in females.
Subject(s)
Female , Humans , Cardiovascular Diseases , Cerebrovascular Disorders , Cohort Studies , Coronary Disease , Demography , Diabetes Complications , Diabetes Mellitus, Type 2 , Diabetic Retinopathy , Dyslipidemias , Hospitals, University , Hypertension , Korea , Nutrition Surveys , Peripheral Vascular Diseases , Prevalence , Prospective StudiesABSTRACT
BACKGROUND: It is known that diabetes and stress are directly or indirectly related, and that it is important to evaluate stress in patients with diabetes. The relationship between Korean diabetics and diabetes-related stress has never been reported. The objective of this study was to develop a stress questionnaire suitable for use with Korean diabetics and to evaluate its utility. METHODS: This study subjects were 307 Korean diabetics, aged 40 to 74 years old, who visited the Department of Endocrinology and Metabolism at Gachon University Gil Hospital, Yeungnam University Medical Center, and Inha University Hospital in Korea between March 2006 and February 2008. We developed a Korean version of Polonsky's Problem Areas in Diabetes (PAID) stress questionnaire (PAID-K) and used it to assess degrees of stress in our sample of Korean patients. We evaluated the utility of the questionnaire and analyzed the relationships between clinical characteristics of the study subjects and degrees of stress. RESULTS: Cronbach's alpha for PAID-K was 0.95, and PAID-K scores were significantly correlated with Hypoglycemia Fear Survey scores (r=0.44, P<0.05) and State Trait Anxiety Inventory-6 scores (r=0.21, P<0.05). PAID-K scores were significantly higher in patients with longer durations of diabetes, patients using insulin, and female patients (P=0.02, P=0.038, and P=0.001, respectively). The score also tended to increase as HbA1c levels increased, except for very high HbA1c levels (above 11%) (P for trend<0.05). CONCLUSION: We developed the PAID-K questionnaire and demonstrated its utility to evaluate levels of stress in diabetic patients in Korea.
Subject(s)
Aged , Female , Humans , Academic Medical Centers , Anxiety , Diabetes Mellitus , Diabetes Mellitus, Type 2 , Endocrinology , Hypoglycemia , Insulin , Korea , Stress, Psychological , Surveys and QuestionnairesABSTRACT
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.
Subject(s)
Humans , Body Weight , Diabetes Mellitus, Type 2 , Diarrhea , Fasting , Glucose , Hyperglycemia , Hypoglycemia , Hypoglycemic Agents , Metformin , Plasma , Sulfonylurea Compounds , ThiazolidinedionesABSTRACT
No abstract available.
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OBJECTIVE: To determine the relations of parameters of nerve conduction study (NCS) and total symptom score (TSS), neuropathy impairment score (NIS) in diabetic polyneuropathy patients. METHOD: Seventy three patients with diabetes mellitus were included in the study. The NIS, TSS was scored in each patient by a single examiner. NCS was performed on median, ulnar, tibial, peroneal and sural nerves. Distal latencies, amplitudes and conduction velocities of compound muscles and nerves were used as parameters of NCS. The transformed individual amplitudes and nerve conduction velocities were graded in relation to the mean values and standard deviations of our control group study. Then, composite score (CS) was calculated in each individual and was correlated to the NIS, TSS using correlation analysis. RESULTS: There was a significant linear relationship between CS and NIS-LL (neuropathy impairment score-lower limb) (r=0.718, p<0.01) CONCLUSION: This study showed significant correlations between composite score and NIS-LL. Thus, composite score appears to reliably represent the objective neurologic findings. In addition, NIS-LL would be useful in determining the progression of peripheral polyneuropathy in diabetic patients.
Subject(s)
Humans , Diabetes Mellitus , Diabetic Neuropathies , Muscles , Neural Conduction , Neurologic Manifestations , Organic Chemicals , Polyneuropathies , Sural NerveABSTRACT
BACKGROUND: Type 2 diabetes mellitus is a common, chronic and costly disease. Its prevalence is rapidly increasing worldwide. Diabetes has big economic burden mainly because of its chronic complications. We analyzed the annual direct medical costs of type 2 diabetic patients, including the costs associated with its complications in Korea retrospectively. METHODS: We enrolled 531 type 2 diabetic patients who had been treated in the 3 Tertiary Hospital in 2005. Clinical characteristics, duration of diabetes, modality of glycemic control, and presence of microvascular and macrovascular complications were assessed by the review of medical records. The annual direct medical costs were assessed using the hospital electronic database and included insurance covered and uncovered medical costs. RESULTS: The annual direct medical costs of type 2 diabetic patients without any complications was 1,184,563 won (95% CI for mean: 973,006~1,396,121 won). Compared to diabetic patients without complications, annual total medical costs increased 4.7-fold, 10.7-fold, and 8.8-fold in patients with microvascular complications, macrovascular complications and both complications, respectively. Hospitalization costs largely increased by 78.7-fold and 61.0-fold in patients with macrovascular complications and both complications, respectively. Major complications to increase medical costs were kidney transplantation (23.1-fold), dialysis (21.0-fold), PTCA or CABG (12.4-fold), and leg amputation (11.8-fold). The total medical costs dramatically increased according to the stage of diabetic retinopathy and nephropathy. CONCLUSION: Diabetic complications have a substantial impact on the direct medical costs of type 2 diabetic patients. The prevention of diabetic complications will benefit the patients as well as the overall healthcare expenditures.
Subject(s)
Humans , Amputation, Surgical , Delivery of Health Care , Diabetes Complications , Diabetes Mellitus, Type 2 , Diabetic Retinopathy , Dialysis , Electronics , Electrons , Health Expenditures , Hospitalization , Insurance , Kidney Transplantation , Korea , Leg , Medical Records , Prevalence , Tertiary Care CentersABSTRACT
BACKGROUND: The objective of the present study was to examine the association of educational level and socioeconomic status with glucose metabolism including prediabetes. METHODS: This cross-sectional study subjects were 882 (mean age: 51.0 +/- 13.4 years, M:F = 241:641) without diabetes, aged more than 20 years and residing in Whasu 2 dong in Incheon. We classified them into three levels according to their educational level: primary (illiterate or up to elementary school), secondary (middle school or high school) and tertiary (university), and into three levels according to their socioeconomic status by self reported questionnaire: low, middle and high. Subjects were diagnosed as three groups (normal, prediabetes and diabetes) by American Diabetes Association criteria using 75 g oral glucose tolerance test. The association of educational level and socioeconomic status with glucose metabolism was analyzed. RESULTS: The number of normal group was 300 (34.0%), that of prediabetes was 470 (53.3%) and that of diabetes was 112 (12.7%). In women, the proportion of primary educational group was larger than that of secondary educational group in diabetes (Odds ratio [OR] = 1.88; 95% confidence interval [CI]: 1.01-3.51) and larger than that of tertiary educational group in prediabetes ([OR] = 2.00; [CI]: 1.06-3.78). But socioeconomic status did not have the statistical association with glucose metabolism in women. Also both educational level and socioeconomic status had no statistical association with glucose metabolism in men. CONCLUSIONS: The proportion of low educational level is larger in prediabetes and diabetes compared with normal group in women.
Subject(s)
Aged , Female , Humans , Cross-Sectional Studies , Glucose , Glucose Tolerance Test , Prediabetic State , Self Report , Social ClassABSTRACT
Cushing's syndrome associated with nodular adrenal hyperplasia glands is divided into 4 main categories: adrenal adenoma, adrenal carcinoma, primary pigmented nodular adrenal dysplasia and macronodular adrenal hyperplasia(MAH). The mechanism of bilateral MAH, when ACTH is suppressed, was previously unknown, and referred to as being "autonomous". Recently, several reports have shown MAH to be under the control of ectopic or eutopic membrane hormone. Here, a case of Cushing's syndrome, caused by bilateral MAH, is reported. A 62-year-old woman presented with Cushingoid features, hypertension and diabetes mellitus. In her case, abnormal adrenal stimulation of cortisol secretion in response to exogenous vasopression stimulation was shown. Her urine free cortisol was 726.0microgram/dL, which was not suppressed after administration of high-dose dexamethasone. Her plasma cortisol level was elevated, but without circadian rhythm. ACTH was undetectable. An abdomen CT scan demonstrated bilaterally enlarged multinodular adrenal glands. A Sella MRI revealed no alteration of the pituitary gland. The patient underwent a laparoscopic bilateral adrenalectomy. Histological examination revealed bilateral macronodular hyperplasia. After having recovered, the patient showed progressive regression of the Cushingoid status.
Subject(s)
Female , Humans , Middle Aged , Abdomen , Adenoma , Adrenal Glands , Adrenalectomy , Adrenocorticotropic Hormone , Circadian Rhythm , Cushing Syndrome , Dexamethasone , Diabetes Mellitus , Hydrocortisone , Hyperplasia , Hypertension , Magnetic Resonance Imaging , Membranes , Pituitary Gland , Plasma , Tomography, X-Ray Computed , VasopressinsABSTRACT
The familial occurrence of a pituitary adenoma associated with multiple endocrine neoplasia (MEN) type 1 or Carney complex is a well-recognized entity. However, an isolated familial somatotropinoma is a rare inherited disease, which is characterized by clustering of a somatotrophic adenoma and acromegaly or gigantism in a family, but without other manifestations of MEN type 1, with only 68 cases, in 28 families, described in the literature. The mode of inheritance is autosomal dominant, with incomplete penetration, but the genetic background of these pituitary adenomas remains unknown. A family exists where both the father and son were affected. Endocrinological investigations confirmed hypersecretion of GH and IGF-1, and the pituitary adenomas were identified by magnetic resonance image in both cases. There was no symptom of MEN type 1 or other form of endocrine dysfunction. Herein is reported a case of an isolated familial somatotropinoma in Korea, with a review of the literature
Subject(s)
Humans , Male , Acromegaly , Adenoma , Carney Complex , Fathers , Gigantism , Growth Hormone-Secreting Pituitary Adenoma , Insulin-Like Growth Factor I , Korea , Multiple Endocrine Neoplasia , Pituitary Neoplasms , Somatotrophs , WillsABSTRACT
The familial occurrence of a pituitary adenoma associated with multiple endocrine neoplasia (MEN) type 1 or Carney complex is a well-recognized entity. However, an isolated familial somatotropinoma is a rare inherited disease, which is characterized by clustering of a somatotrophic adenoma and acromegaly or gigantism in a family, but without other manifestations of MEN type 1, with only 68 cases, in 28 families, described in the literature. The mode of inheritance is autosomal dominant, with incomplete penetration, but the genetic background of these pituitary adenomas remains unknown. A family exists where both the father and son were affected. Endocrinological investigations confirmed hypersecretion of GH and IGF-1, and the pituitary adenomas were identified by magnetic resonance image in both cases. There was no symptom of MEN type 1 or other form of endocrine dysfunction. Herein is reported a case of an isolated familial somatotropinoma in Korea, with a review of the literature
Subject(s)
Humans , Male , Acromegaly , Adenoma , Carney Complex , Fathers , Gigantism , Growth Hormone-Secreting Pituitary Adenoma , Insulin-Like Growth Factor I , Korea , Multiple Endocrine Neoplasia , Pituitary Neoplasms , Somatotrophs , WillsABSTRACT
Hyponatremia is a frequent condition of body fluid and electrolyte imbalance encountered in clinical practice. However, rhabdomyolysis has rarely been reported in association with hyponatremia. We experienced a 56-year-old woman who had developed symptomatic hyponatremia after prolonged nausea and subsequent rhabdomyolysis. Hyponatremia was probably mediated by hypersecretion of antidiuretic hormones.The woman had developed severe hypotonic hyponatremia with an alternation in mental status after suffering from severe nausea and vomiting for x months/years. She recovered with intensive supportive therapy, including hypertonic saline administration. One day after hospitalization, she complained of thigh pains; furthermore her serum creatine phosphokinase level had increased. She was treated with alkaline diuresis. Renal failure or compartment syndrome did not complicate the clinical course. The patient was discharged and returned to her normal daily activities. The possibility of rhabdomyolysis should be considered in patients with acute hyponatremia who have developed muscle pain.
Subject(s)
Female , Humans , Middle Aged , Body Fluids , Compartment Syndromes , Creatine Kinase , Diuresis , Hospitalization , Hyponatremia , Myalgia , Nausea , Renal Insufficiency , Rhabdomyolysis , Thigh , VomitingABSTRACT
Clinically detectable metastatic follicular thyroid carcinoma to the thymus is very rare in the literature and sometimes confused with false positive uptake of Iodine
Subject(s)
Adult , Female , Humans , Adenocarcinoma, Follicular/secondary , Iodine Radioisotopes , Thymus Neoplasms/secondary , Thyroid Neoplasms/pathology , Tomography, Emission-ComputedABSTRACT
Osteoporosis imperfecta (OI) is a genetic disorder characterized by fragility of bone, deafness, blue sclerae; and laxity of joints. Four types of OI are distinguished by clinical findings. Although mutations affecting collagen I are responsible for the disease in the most patients, the mechanism by which the genetic defects cause abnormal bone development has not been well established. Therefore we evaluated static and dynamic bone histomorphometry of type I OI in the case study of a 15 year old boy with OI who had blue sclerae, a history of frequent fracture and a familial history of blue sclerae. Biopsy of the ilium showed loss of connection between the cortical bone and trabecular bones. The Harversian system in the cortical bone was poorly developed. In the trabecular bones, the lamellar pattern was poorly developed. Mineral apposition rate of the cortical bone was 1.0 m/day and of the trabecular bone was 0.79 m/day. Thus OI might be regard as a disease whereby abnormal collagen synthesis interferes with bone strength by multiple mechanisms.
Subject(s)
Adolescent , Humans , Male , Biopsy , Bone Development , Collagen , Deafness , Ilium , Joints , Osteogenesis Imperfecta , Osteogenesis , Osteoporosis , ScleraABSTRACT
No abstract available.