• Diabetes and Metabolism Journal
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• v.42 no.6
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• pp.496-512
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• 2018

Background: This study aimed to investigate the association between the presence and severity of cardiovascular autonomic neuropathy (CAN) and development of long-term glucose fluctuation in subjects with type 2 diabetes mellitus. Methods: In this retrospective cohort study, subjects with type 2 diabetes mellitus who received cardiovascular autonomic reflex tests (CARTs) at baseline and at least 4-year of follow-up with ${\geq}6$ measures of glycosylated hemoglobin (HbA1c) were included. The severity of CAN was categorized as normal, early, or severe CAN according to the CARTs score. HbA1c variability was measured as the standard deviation (SD), coefficient of variation, and adjusted SD of serial HbA1c measurements. Results: A total of 681 subjects were analyzed (294 normal, 318 early, and 69 severe CAN). The HbA1c variability index values showed a positive relationship with the severity of CAN. Multivariable logistic regression analysis showed that CAN was significantly associated with the risk of developing higher HbA1c variability (SD) after adjusting for age, sex, body mass index, diabetes duration, mean HbA1c, heart rate, glomerular filtration rate, diabetic retinopathy, coronary artery disease, insulin use, and anti-hypertensive medication (early CAN: odds ratio [OR], 1.65; 95% confidence interval [CI], 1.12 to 2.43) (severe CAN: OR, 2.86; 95% CI, 1.47 to 5.56). This association was more prominent in subjects who had a longer duration of diabetes (>10 years) and lower mean HbA1c (<7%). Conclusion: CAN is an independent risk factor for future higher HbA1c variability in subjects with type 2 diabetes mellitus. Tailored therapy for stabilizing glucose fluctuation should be emphasized in subjects with CAN.

• Journal of Chest Surgery
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• v.53 no.5
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• pp.277-284
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• 2020

Background: Cardiac arrest during or after office-based cosmetic surgery is rare, and little is known about its prognosis. We assessed the clinical outcomes of patients who developed cardiac arrest during or after cosmetic surgery at office-based clinics. Methods: Between May 2009 and May 2016, 32 patients who developed cardiac arrest during or after treatment at cosmetic surgery clinics were consecutively enrolled. We compared clinical outcomes, including complications, between survivors (n=19) and non-survivors (n=13) and attempted to determine the prognostic factors of mortality. Results: All 32 of the patients were female, with a mean age of 30.40±11.87 years. Of the 32 patients, 13 (41%) died. Extracorporeal life support (ECLS) was applied in a greater percentage of non-survivors than survivors (92.3% vs. 47.4%, respectively; p=0.009). The mean duration of in-hospital cardiopulmonary resuscitation (CPR) was longer for the non-survivors than the survivors (31.55±33 minutes vs. 7.59±9.07 minutes, respectively; p=0.01). The mean Acute Physiology and Chronic Health Evaluation score was also higher among non-survivors than survivors (23.85±6.68 vs. 16.79±7.44, respectively; p=0.01). No predictor of death was identified in the patients for whom ECLS was applied. Of the 19 survivors, 10 (52.6%) had hypoxic brain damage, and 1 (5.3%) had permanent lower leg ischemia. Logistic regression analyses revealed that the estimated glomerular filtration rate was a predictor of mortality. Conclusion: Patients who developed cardiac arrest during or after cosmetic surgery at office-based clinics experienced poor prognoses, even though ECLS was applied in most cases. The survivors suffered serious complications. Careful monitoring of subjects and active CPR (when necessary) in cosmetic surgery clinics may be essential.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.43 no.1
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• pp.16-22
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• 2017

Objectives: Bisphosphonate is the primary cause of bisphosphonate-related osteonecrosis of the jaw (BRONJ). Bisphosphonates are eliminated from the human body by the kidneys. It is anticipated that bisphosphonate levels in the body will increase if the kidney is in a weak state or if there is systemic disease that affects kidney function. The aim of this study was to analyze the relevance of renal function in the severity of BRONJ. Materials and Methods: Ninety-three patients diagnosed with BRONJ in Pusan National University Dental Hospital from January 2012 to December 2014 were included in this study. All patients underwent a clinical exam, radiographs, and serologic lab test, including urine analysis. The patient's medical history was also taken, including the type of bisphosphonate drug, the duration of administration and drug holiday, route of administration, and other systemic diseases. In accordance with the guidelines of the 2009 position paper of American Association of Oral and Maxillofacial Surgeons, the BRONJ stage was divided into 4 groups, from stage 0 to 3, according to the severity of disease. IBM SPSS Statistics version 21.0 (IBM Co., USA) was used to perform regression analysis with a 0.05% significance level. Results: BRONJ stage and renal factor (estimated glomerular filtration rate) showed a moderate statistically significant correlation. In the group with higher BRONJ stage, the creatinine level was higher, but the increase was not statistically significant. Other factors showed no significant correlation with BRONJ stage. There was a high statistically significant correlation between BRONJ stage and 'responder group' and 'non-responder group,' but there was no significant difference with the 'worsened group.' In addition, the age of the patients was a relative factor with BRONJ stage. Conclusion: With older age and lower renal function, BRONJ is more severe, and there may be a decrease in patient response to treatment.

• The Korean Journal of Pharmacology
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• v.18 no.1
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• pp.1-10
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• 1982

In an attempt to delineate the role of beta-adrenoceptors found to be existing in the brain tissue in the central regulation of renal function, isoproterenol, a ${\beta}-adrenergic$ agonist, was administered directly into a lateral ventricle of the rabbit brain and the changes of renal function were observed. Also, the effects of propranolol, a specific ${\beta}-adrenergic$ blocking agent, and its influence upon the isoproterenol action were studied. Isoproterenol, in doses ranging from 5 to $50\;{\mu}g/kg\;i.c.v.$, elicited antidiuresis which seemed to be related to the decreased renal hemodynamics brought about by the systemic hypotension. With moderate doaes of $15\;{\mu}g/kg$ the antidiuresis was less prominent and there was a tendency toward natriuresis, but with higher doses the natriuretic effect became less evident, overrun by the systemic hypotension. Propranolol, $500\;{\mu}g/kg\;i.c.v.$, produced little effect on the renal function, but it eliminated the antidiuretic action of $50\;{\mu}g/kg$ isoproterenol i.c.v. and reversed it to a diuretic and natriuretic one, along with increases in renal plasma flow and glomerular filtration rate. The systemic hypotension also was markedly attenuated by propranolol pretreatment. Thus, it was evident that the renal action of i.c.v. isoproterenol was not blocked by propranolol and became explicit only when the hypotensive action of isoproterenol which seems to he propranolol-sensitive is removed. Various possibilities to account for this disparity in sensitivity were discussed. It is suggested from these observations that the central ${\beta}-adrenoceptors$ might also be involved in the regulation of renal function along with ${\alpha}-adrenoceptors$, though less significant than the latter.

• YAKHAK HOEJI
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• v.34 no.4
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• pp.238-243
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• 1990

Pharmacokinetic characteristics of recombinant human interleukin-2 (rH IL-2) wre studied in the rat. First, different doses of rH IL-2 ranging from 6,400 to 1,600,000 U/kg were injected intravenously and the effect of dose size on the pharmacokinetics was examined. There was no dose dependency in the pharmacokinetics of rHIL-2 in the dose range of 6,400-40,000 U/kg. But at the dose of 1,600,000 U/kg, there was a severe hemolysis throughout the experiment and the pharmacokinetic parameters such as Vdss and CLt were significantly increased compared to those obtained from lower doses. It also showed that this drug is hardly distributed to the peripheral tissues and hardly eliminated from the body, since the valume of distribution (Vdss) and total body clearance (CLt) were 45-75 ml/kg and 1-2 ml/min/kg, respectively. The Vdss is close to the actual plasma volume and the CLt is less than glomerular filtration rate (GFR). Therefore it seemed that rH IL-2 is distributed only in the plasma pool and hardly filtered in the kidney due to its very large molecular weight. Second, rH IL-2 was administered to the rat via several routes such as hepatic portal vein (PV), intraperitoneal (IP), peroral (PO) and intranasal (IN) routes. The bioavailabilities (BA) of PV, IP, PO and IN routes were 96.8, 4.9, 0 and 0.1%, respectively. The addition of some nasal absorption enhancers such as taurocholate, taurodeoxycholate, glycocholate and glycodeoxycholate did not increase the BA of intranasaly administered rH IL-2. The result is contrast to the effect of these bile salts on the nasal absorption of ${\alpha}-inteferon$. Considering it together with the pharmacokinetic parameters, very large molecular weight of rH IL-2 seemed again to be the cause to very poor membrane permeability.

• Journal of Periodontal and Implant Science
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• v.30 no.2
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• pp.359-374
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• 2000

Cyclosporine A(CsA) is a widely used immunosuppressant for transplant patients and is also used for the treatment of a wide variety of systemic diseases with immunologic disorders. However, its use is frequently limited because of complications such as nephrotoxicity or gingival hyperplasia. Although several hypotheses have been postulated for CsA-induced gingival hyperplasia, i.e. various cytokine effects of inflammatory cells, existence of plaque or CsA itself, but its pathogenesis is still unclear. For experimental chronic CsA toxicity, salt depletion has been shown to increased susceptibility of rodents to the effects of CsA, and this maneuver facilitates production of arteriolopathy and interstitial fibrosis in kidney that mimic the changes found in human. The purpose of this study was to evaluate pathogenesis of CsA-induced gingival hyperplasia by comparing changes between CsA administration groups of normal standard diet and those of low salt diet group. Specific pathogen-free, 20 to 25 days old(120 to 150 g), male Fisher-344 rats(KIST, Korea), 120 to 150g of body weight, were assigned to four groups of six animals each after one week of adaptation period for powder food. Group 1 received olive oil($300{\mu}l/g\;of\;diet$) with normal standard diet(0.4% of sodium)(NSD). Group 2 received CsA(Cypol-N, Jonggundang, Korea; $300{\mu}g/g\;of\;diet$) with normal standard diet(NSD+CsA). Group 3 received same amount of olive oil with low salt diet(0.05 % of sodium, Teklad Premier, U.S.A.)(LSD). Group 4 received same dose of CsA with low salt diet(LSD+CsA). Rats were pair fed and were sacrificed after six weeks. Renal histologic lesions associated with CsA, consisted of cortical interstitial fibrosis, tubular atrophy and hyalinization of arterioles and the impairment of renal function including increase of serum creatinine and decrease of glomerular filtration rate was more severe in low salt diet group. These were proved as the results of activated of renin-angiotensin system in the kidney by low salt condition. Meanwhile the degree of gingival hyperplasia at incisor and molar tooth was less severe in low salt diet group compared with normal sodium diet group. Hyperplastic gingiva showed mild epithelial hyperplasia and expanded underlyng stroma which consisted of matrix increasement, capillary proliferation and dilatation. While the number and the activation of fibroblasts were increased, inflammatory cells were rare in the stroma. The immunohistochemistry for TGF-${\beta}_1$ in the kidney and gingiva revealed stronger positive in LSD+CsA in kidney but in gingiva of NSD+CsA. These results suggested followings; Gingival hyperplasia can be developed without inflammatory cells infiltration and seemed not induced by CsA by itself. The major role for gingival hyperplasia by CsA would be the secondary effect of TGF-${\beta}$, which maybe upregulated by CsA administration. Low salt diet can attenuate this hyperplasia perhaps by decreasing the activation of $TGF-{\beta}$.

• Clinical and Experimental Pediatrics
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• v.58 no.11
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• pp.421-426
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• 2015

Purpose: The vancomycin dosage regimen is regularly modified according to the patient's glomerular filtration rate (GFR). In the present study, we aimed to assess the usefulness of serum cystatin C (Cys-C) concentration, compared with serum creatinine (SCr) concentration, for predicting vancomycin clearance (CLvcm) in neonates. Methods: We retrospectively analyzed the laboratory data of 50 term neonates who were admitted to the neonatal intensive care unit and received intravenous vancomycin, and assessed the pharmacokinetic profiles. Creatinine clearance (CLcr) and GFR based on Cys-C (GFRcys-c) were estimated using the Schwartz and Larsson formulas, respectively. Results: The mean CLvcm (${\pm}$standard deviation) was $74.52{\pm}31.17L/hr$, the volume of distribution of vancomycin was $0.67{\pm}0.14L$, and vancomycin half-life was $9.16{\pm}17.42hours$. The SCr was $0.46{\pm}0.25mg/dL$ and serum Cys-C was $1.43{\pm}0.34mg/L$. The peak and trough concentrations of vancomycin were $24.65{\pm}14.84$ and $8.10{\pm}5.35mcg/mL$, respectively. The calculated GFR based on serum creatinine concentration (GFR-Cr) and GFRcys-c were $70.2{\pm}9.45$ and $63.6{\pm}30.18mL/min$, respectively. The correlation constant for CLvcm and the reciprocal of Cys-C (0.479, P=0.001) was significantly higher than that for CLvcm and the reciprocal of SCr (0.286, P=0.044). GFRcys-c was strongly correlated with CLvcm (P=0.001), and the correlation constant was significantly higher than that for CLvcm and CLcr (0.496, P=0.001). Linear regression analysis showed that only GFRcys-c was independently and positively correlated with CLvcm (F=41.9, P<0.001). Conclusion: The use of serum Cys-C as a marker of CLvcm could be beneficial for more reliable predictions of serum vancomycin concentrations, particularly in neonates.

• Journal of dental hygiene science
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• v.17 no.2
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• pp.160-167
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• 2017

The purpose of this systematic review was to investigate the association between periodontal disease and chronic kidney disease. A search of Embase, PubMed and The Cochrane Library databases was performed up to April 17, 2016. Article selection was based on cohort study design and the study subjects were patients with periodontal disease or severe periodontal disease. The final result was development of chronic kidney disease and kidney function decrease based on the estimated glomerular filtration rate values. The quantitative synthesis of the final selected articles was assessed using Review Manager statistical analysis software. A fixed-effects model meta-analysis was performed to estimate the degree of association between periodontal disease and chronic kidney disease. The search strategy identified 3,018 potentially eligible articles, of these, four studies were finally selected for meta-analysis, revealing that periodontal disease was significantly associated with the risk of developing chronic kidney disease (odds ratio, 1.65; 95% confidence interval, 1.44~1.90; p<0.001). In order to prevent the development of chronic kidney disease and kidney function decrease it is important to prevent periodontal disease, as well as minimizing the traditional risk factors known to reduce the quality of life of patients and increase disease burden.

• Journal of Chest Surgery
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• v.47 no.3
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• pp.240-248
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• 2014

Background: Open heart surgery using cardiopulmonary bypass (CPB) is considered one of the most frequent surgical procedures in which acute kidney injury (AKI) is a frequent and serious complication. The aim of the present study was to evaluate the efficiency of neutrophil gelatinase-associated lipocalin (NGAL) as an early AKI biomarker after CPB in cardiac surgery (CS). Methods: Thirty-seven adult patients undergoing CS with CPB were included in this retrospective study. They had normal preoperative renal function, as assessed by the creatinine (Cr) level, NGAL level, and estimated glomerular filtration rate. Serial evaluation of serum NGAL and Cr levels was performed before, immediately after, and 24 hours after the operation. Patients were divided into two groups: those who showed normal immediate postoperative serum NGAL levels (group A, n=30) and those who showed elevated immediate postoperative serum NGAL levels (group B, n=7). Statistical analysis was performed using Statistical Package for the Social Sciences version 18. Results: Of the 37 patients, 6 (6/37, 16.2%) were diagnosed with AKI. One patient belonged to group A (1/30, 3.3%), and 5 patients belonged to group B (5/7, 71.4%). Two patients in group B (2/7, 28.5%) required further renal replacement therapy. Death occurred in only 1 patient (1/37, 2.7%), who belonged to group B. Conclusion: The results of this study suggest that postoperative plasma NGAL levels can be used as an early biomarker for the detection of AKI following CS using CPB. Further studies with a larger sample size are needed to confirm our results.

• Kidney Research and Clinical Practice
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• v.36 no.1
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• pp.48-57
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• 2017

Background: Hepatic steatosis measured with controlled attenuation parameter (CAP) using transient elastography predicts metabolic syndrome in the general population. We investigated whether CAP predicted metabolic syndrome in chronic kidney disease patients. Methods: CAP was measured with transient elastography in 465 predialysis chronic kidney disease patients (mean age, 57.5 years). Results: The median CAP value was 239 (202-274) dB/m. In 195 (41.9%) patients with metabolic syndrome, diabetes mellitus was more prevalent (105 [53.8%] vs. 71 [26.3%], P < 0.001), with significantly increased urine albumin-to-creatinine ratio (184 [38-706] vs. 56 [16-408] mg/g Cr, P = 0.003), high sensitivity C-reactive protein levels (5.4 [1.4-28.2] vs. 1.7 [0.6-9.9] mg/L, P < 0.001), and CAP (248 [210-302] vs. 226 [196-259] dB/m, P < 0.001). In multiple linear regression analysis, CAP was independently related to body mass index (${\beta}=0.742$, P < 0.001), triglyceride levels (${\beta}=2.034$, P < 0.001), estimated glomerular filtration rate (${\beta}=0.316$, P = 0.001), serum albumin (${\beta}=1.386$, P < 0.001), alanine aminotransferase (${\beta}=0.064$, P = 0.029), and total bilirubin (${\beta}=-0.881$, P = 0.009). In multiple logistic regression analysis, increased CAP was independently associated with increased metabolic syndrome risk (per 10 dB/m increase; odds ratio, 1.093; 95% confidence interval, 1.009-1.183; P = 0.029) even after adjusting for multiple confounding factors. Conclusion: Increased CAP measured with transient elastography significantly correlated with and could predict increased metabolic syndrome risk in chronic kidney disease patients.