Seropositive rate of the anti-hepatitis A immunoglobulin G antibody in maintenance hemodialysis subjects from two hospitals in Korea

BACKGROUND/AIMS@#Hepatitis A virus (HAV) is a self-limiting infectious disease, but 1% of subjects develop fulminant hepatitis. The prevalence of the anti-HAV immunoglobulin G (IgG) antibody in hemodialysis subjects in Korea remains unknown. The purpose of this study was to describe and compare the seropositive rate of anti-HAV antibody among hemodialysis subjects in two hospitals according to age group.@*METHODS@#A total of 170 hemodialysis subjects were evaluated for the seropositive rate of the anti-HAV IgG antibody and its titer.@*RESULTS@#Of the 170 maintenance hemodialysis subjects in two hospitals (Kangnam 92 vs. Chuncheon 78), 79 (46.5%) were male. The mean age was 53.2 years old, and 94.1% of the subjects were over 40 years old. The median vintage of hemodialysis was 29.0 months. Anti-HAV antibody was found in 163 subjects (95.9%), with no significant difference between the two areas (Kangnam 97.8% [n = 90] vs. Chuncheon 93.6% [n = 73]). Subjects younger than 40 years old showed a seropositive rate of 50%, while the seropositive rate increased with age for subjects aged 40 or older (p for trend < 0.001). Seropositive subjects from Kangnam showed a higher anti-HAV antibody titer than those from Chuncheon (median: Kangnam 14.2 vs. Chuncheon 11.7). Only age influenced seropositivity. The only factor that influenced the antibody level was the location of hospital (p < 0.001).@*CONCLUSIONS@#The seropositive rate of the anti-HAV antibody in hemodialysis subjects was 95%, which is similar to findings in the general population. Active immunization against hepatitis A is strongly recommended for hemodialysis subjects under 40 years of age after anti-HAV testing.

Effects of aspirin resistance and mean platelet volume on vascular access failure in hemodialysis patients

BACKGROUND/AIMS@#Maintaining the patency of vascular access (VA) in hemodialysis (HD) patients is important and can be life-saving. We investigated the effects of aspirin resistance and mean platelet volume (MPV) on VA failure in HD patients.@*METHODS@#We enrolled 163 patients on maintenance HD. VA failure was defined as thrombosis or a decrease of > 50% of the normal vessel diameter, as revealed by angiography.@*RESULTS@#Aspirin resistance was observed in 17 of 109 patients in whom this parameter was measured, and was not significantly associated with VA failure (p = 0.051). The mean MPV was 9.15 ± 0.05 fL. The 163 patients were grouped by the median MPV value (9.08 fL) at baseline; patients with higher MPVs (n = 82) had lower platelet counts (p = 0.002) and albumin levels (p = 0.009). During 34 months of follow-up, 65 VA failures (39.9%) occurred. The Kaplan-Meier curve revealed significant differences between the two groups in terms of cumulative VA failure (54.1% vs. 35.3%, p = 0.018). On multivariate analysis, the MPV (hazard ratio [HR], 1.794; 95% confidence interval [CI], 1.066 to 3.020; p = 0.028), platelet count (HR, 1.003; 95% CI, 1.001 to 1.006; p = 0.01), and smoking status (HR, 1.894; 95% CI, 1.019 to 3.519; p = 0.043) independently predicted VA failure.@*CONCLUSIONS@#A high MPV was associated with an increased risk of VA failure, whereas aspirin resistance showed only a weak association. The MPV may predict VA survival in HD patients.

Comparisons of CTX-M-Producing Escherichia coli Isolates from Humans and Animals in South Korea

To investigate the possibility of transmission of CTX-M-producing Escherichia coli isolates among humans and animals, we compared CTX-M-producing E. coli isolates showing the same genotype from humans and dogs in Korea. Sixteen CTX-M-producing E. coli isolates from animals were selected and their genotypes were identified using MLST. Among clinical CTX-M-producing E. coli isolates from humans, which have been identified in previous studies, 12 isolates showing the same STs with those of E. coli isolates from animals were selected. For these 28 CTX-M-producing E. coli isolates, identification of bla CTX-M genes and their genetic environments, antimicrobial susceptibility testing, extended MLST, and PFGE were performed. Some CTX-M-producing E. coli isolates from humans showed the same genotypes, such as ST10, ST38, ST58, and ST95, but different CTX-M enzymes and PFGE patterns. Thus, it can be concluded that dissemination of ESBL-producing E. coli isolates between humans and animals is rare so far.

Clostridium difficile-associated diarrhea in dialysis patients

BACKGROUND: Dialysis patients have impaired host defense mechanisms and frequently require antibiotics for various infective complications. In this study, we investigated whether dialysis patients have greater risk for Clostridium difficile-associated diarrhea (CDAD). METHODS: During the 4-year study period (2004-2008), 85 patients with CDAD were identified based on a retrospective review of C difficile toxin assay or histology records. Nosocomial diarrheal patients without CDAD were considered as controls (n=403). We assessed the association between renal function and the prevalence and clinical outcomes of CDAD. RESULTS: There was a significant difference in the prevalence rate of chronic kidney disease (CKD) between CDAD and non-CDAD patients (P<0.001). Sixteen patients (18.8%) of the CDAD group were treated with dialysis, whereas 21 patients (5.2%) of the non-CDAD group were treated with dialysis. There was a significant association between renal function and CDAD in patients on dialysis [odds ratio (OR)=4.44, 95% confidence interval (CI) 2.19-8.99, P<0.001], but not in patients with CKD stage 3-5 (OR=1.10, 95% CI 0.63-1.92, P=0.73). In multivariate analysis, CKD stage 5D was an independent risk factor for the development of CDAD (OR=13.36, 95% CI 2.94-60.67, P=0.001). CONCLUSION: Our data indicate that dialysis patients might be at a greater risk of developing CDAD, which suggests that particular attention should be provided to CDAD when antibiotic treatment is administered to dialysis patients.

Clostridium difficile-associated diarrhea in dialysis patients

BACKGROUND: Dialysis patients have impaired host defense mechanisms and frequently require antibiotics for various infective complications. In this study, we investigated whether dialysis patients have greater risk for Clostridium difficile-associated diarrhea (CDAD). METHODS: During the 4-year study period (2004-2008), 85 patients with CDAD were identified based on a retrospective review of C difficile toxin assay or histology records. Nosocomial diarrheal patients without CDAD were considered as controls (n=403). We assessed the association between renal function and the prevalence and clinical outcomes of CDAD. RESULTS: There was a significant difference in the prevalence rate of chronic kidney disease (CKD) between CDAD and non-CDAD patients (P<0.001). Sixteen patients (18.8%) of the CDAD group were treated with dialysis, whereas 21 patients (5.2%) of the non-CDAD group were treated with dialysis. There was a significant association between renal function and CDAD in patients on dialysis [odds ratio (OR)=4.44, 95% confidence interval (CI) 2.19-8.99, P<0.001], but not in patients with CKD stage 3-5 (OR=1.10, 95% CI 0.63-1.92, P=0.73). In multivariate analysis, CKD stage 5D was an independent risk factor for the development of CDAD (OR=13.36, 95% CI 2.94-60.67, P=0.001). CONCLUSION: Our data indicate that dialysis patients might be at a greater risk of developing CDAD, which suggests that particular attention should be provided to CDAD when antibiotic treatment is administered to dialysis patients.

Rhabdomyolysis and Acute Kidney Injury Associated with Hypothyroidism and Statin Therapy

Rhabdomyolysis is a syndrome involving the breakdown of skeletal muscle that causes myoglobin and other intracellular proteins to leak into the circulatory system, resulting in organ injury including acute kidney injury. We report a case of statin-induced rhabdomyolysis and acute kidney injury that developed in a 63-year-old woman with previously undiagnosed hypothyroidism. Untreated hypothyroidism may have caused her hypercholesterolemia requiring statin treatment, and it is postulated that statin-induced muscle injury was aggravated by hypothyroidism resulting in her full-blown rhabdomyolysis. Although this patient was successfully treated with continuous venovenous hemofiltration and L-thyroxin replacement, rhabdomyolysis with acute kidney injury is a potentially life-threatening disorder. Physicians must pay special attention to the possible presence of subclinical hypothyroidism when administering statins in patients with hypercholesterolemia.

Rhabdomyolysis and Acute Kidney Injury Associated with Hypothyroidism and Statin Therapy

Rhabdomyolysis is a syndrome involving the breakdown of skeletal muscle that causes myoglobin and other intracellular proteins to leak into the circulatory system, resulting in organ injury including acute kidney injury. We report a case of statin-induced rhabdomyolysis and acute kidney injury that developed in a 63-year-old woman with previously undiagnosed hypothyroidism. Untreated hypothyroidism may have caused her hypercholesterolemia requiring statin treatment, and it is postulated that statin-induced muscle injury was aggravated by hypothyroidism resulting in her full-blown rhabdomyolysis. Although this patient was successfully treated with continuous venovenous hemofiltration and L-thyroxin replacement, rhabdomyolysis with acute kidney injury is a potentially life-threatening disorder. Physicians must pay special attention to the possible presence of subclinical hypothyroidism when administering statins in patients with hypercholesterolemia.

Persister Cells: Survival Strategies under Antimicrobiotic Stress

Persistence is dormant phenotypic variants of regular cells that are tolerant to antibiotics. The persistent cells did not acquire antibiotic resistance genetically, being produced in response to antibiotic stress. Because of dormant phenotypic variants due to little or no cell-wall synthesis, translation, or topoisomerase activity, persistent cells show antibiotic tolerance. Recently, such persistent cells have been reported in many bacterial pathogens and are known to play significant roles in clinical settings, particularly in chronic diseases such as cystic fibrosis. Therefore, development of anti-persister drug and appropriate antibiotic treatment are required to eliminate the persisters and to prevent the development of antibiotic resistance. Screening of genes related to persister formation would lead to new drugs to combat persisters during infection. By reviewing recent publications, we summarize phenomenon of survival and tolerance in persistent cells.

Adipsic Hypernatremia Associated with Deficiency of Antidiuretic Hormone Release / 대한내과학회지

Adipsic hypernatremia is a rare disorder of hypothalamic osmoreceptor dysfunction for thirst. It is frequently associated with a deficiency in antidiuretic hormone (ADH) release. We report the first case in Korea of adipsic hypernatremia combined with subnormal ADH response to osmotic stimuli without any demonstrable structural lesion. A 69-year-old woman was admitted to the hospital with general weakness. In a hypernatremic hyperosmolar state, she denied thirst and did not drink spontaneously. Her plasma ADH level was markedly subnormal but she had no large volume of dilute urine. Investigation of osmoregulation by infusion of hypertonic saline revealed adipsia and an absolute deficiency in antidiuretic hormone release, despite a serum osmolarity in excess of 321 mOsmol/kg. There was no structural lesion of the hypothalamus and no abnormal finding in hypothalamic-pituitary function. After diagnosis, she was treated successfully with intentional water intake alone.

Successful Management of Fatal Paraquat Poisoning with Four Courses of Steroid and Cyclophosphamide Pulse / 대한내과학회지

Although severe paraquat poisoning is fatal, intensive immunosuppression can be successful in selected patients. We report the case of a 33-yr-old patient who was poisoned by paraquat and developed multi-organ failure, progressive hypoxemia, and pulmonary fibrosis. The patient was successfully treated with four courses of immunosuppressive pulse therapy. The patient presented to the hospital 2.5 hours after ingesting 2 mouthfuls of paraquat. The serum level of paraquat was 10.40 microg/mL at 3 hours and 3.36 microg/mL at 10 hours after ingestion, which is predictive of a fatal outcome. The first course of steroid and cyclophosphamide pulse therapy was initiated after hemoperfusion. During the hospital course, the patient showed progressive hypoxemia with pulmonary fibrosis. Accordingly, three additional courses of immunosuppressive pulse therapy were administered to prevent pulmonary injury. This treatment inevitably led to bone marrow suppression, which was recovered with supportive care. The patient fully recovered after repeated immunosuppressive pulse therapy without residual hypoxemia and was successfully discharged from the hospital.

Characteristics of Acute Pyelonephritis in the Elderly / 대한내과학회지

BACKGROUND/AIMS: Acute pyelonephritis is relatively common in women. It has been well studied in young adults, but rarely in geriatric patients. Given that the population of Korea is aging rapidly, this study examined the clinical characteristics of acute pyelonephritis in Korean geriatric patients. METHODS: We retrospectively studied 499 patients diagnosed with acute community-acquired pyelonephritis from March 2002 to February 2005. All patients admitted to Hallym University Kangnam Sacred Heart Hospital from the emergency room or out-patient department were recruited. Pregnant women and hospital-acquired cases were excluded. RESULTS: Ninety-nine subjects (19.8%) were aged 65 years or over (mean age 73.1 +/- 6.3 years, range 65-93). Elderly patients had a greater male predominance, longer hospital stay, and higher rate of positive urine cultures than patients younger than 65 years. The presence of diabetes mellitus, complicated acute pyelonephritis, and a higher serum creatinine level were associated with geriatric patients. The distribution of infectious microorganisms was similar between the two groups. Old age (> 65 years) was an important risk factor for a long hospital stay, along with male gender, renal dysfunction, white blood count (WBC) and high serum alkaline phosphatase levels. CONCLUSIONS: Geriatric patients with acute pyelonephritis tended to be male, and have diabetes mellitus, renal dysfunction, complicated infections, and a longer duration of hospitalization.

Low-Dose Nafamostat Mesilate in Hemodialysis Patients at High Bleeding Risk / 대한신장학회지

PURPOSE: Systemic anticoagulation, usually with heparin, is required to prevent thrombosis in the blood circuit of hemodialysis. In patients at high bleeding risk, strategies to minimize the bleeding risk include heparin-free or regional anticoagulation methods. Nafamostat mesilate with conventional dose (35 mg/hr) has been used for this purpose. But it is an expensive anticoagulant to use conveniently for the dialysis therapy. Application of low-dose nafamostat mesilate has almost never been tried yet on hemodiaysis management. In this study, we examined the effect of low-dose nafamostat mesilate compared to heparin-free in hemodialysis patients with high risk of bleeding. METHODS: The current study was conducted on 35 hemodialysis patients with high bleeding risk (on-going bleeding, hemorrhage, surgery or severe thrombocytopenia). In the low-dose nafamostat group (n=17, mean age: 59+/-15 years), 238 sessions were performed with continuous infusion of nafamostat mesilate (12.5 mg/hr). In the control group with saline-flushing no heparin methods (n=18, mean age: 57+/-17 years), 247 sessions were analyzed. RESULTS: No significant differences were found in baseline characteristics between the low-dose nafamostat group and the saline group. In the progress of bleeding complications, there were no significant differences between the two groups (11.8% vs. 11.1%). In saline group, however, massive clotting occurred in 44.5 per 1000 sessions, while it occurred in 4.2 per 1000 sessions in the low-dose nafamostat group (p=0.006). CONCLUSION: In patients at high bleeding risk, low-dose nafamostat mesilat can be used as an inexpensive, effective, and safe anticoagulant for hemodialysis.

Aloe-induced Toxic Hepatitis

Aloe has been widely used in phytomedicine. Phytomedicine describes aloe as a herb which has anti-inflammatory, anti-proliferative, anti-aging effects. In recent years several cases of aloe-induced hepatotoxicity were reported. But its pharmacokinetics and toxicity are poorly described in the literature. Here we report three cases with aloe-induced toxic hepatitis. A 57-yr-old woman, a 62-yr-old woman and a 55-yr-old woman were admitted to the hospital for acute hepatitis. They had taken aloe preparation for months. Their clinical manifestation, laboratory findings and histologic findings met diagnostic criteria (RUCAM scale) of toxic hepatitis. Upon discontinuation of the oral aloe preparations, liver enzymes returned to normal level. Aloe should be considered as a causative agent in hepatotoxicity.

Catastrophic antiphospholipid syndrome presenting with disseminated intravascular coagulation, cerebral infarction, and acute respiratory distress syndrome / 대한내과학회지

Antiphospholipid syndrome (APS) is a systemic autoimmune disorder characterized by a combination of arterial or venous thrombosis and recurrent fetal loss accompanied by elevated titers of antiphospholipid antibodies. Catastrophic APS is a small subset of APS, characterized by widespread systemic thrombotic disease with multiorgan failure. The diagnosis of catastrophic APS may be difficult, predominantly due to its frequently atypical presentation. In the present work, we describe a case of a 68-year-old male who presented with cerebral infarction, disseminated intravascular coagulation (DIC), and acute respiratory distress syndrome. The patient was successfully treated with anticoagulants, antibiotics, and steroid therapy. Physicians should be aware of the possibility of this syndrome as a cause of DIC with thrombotic disease because prompt recognition is essential for effective treatment.

Catastrophic antiphospholipid syndrome presenting with disseminated intravascular coagulation, cerebral infarction, and acute respiratory distress syndrome / 대한내과학회지

Antiphospholipid syndrome (APS) is a systemic autoimmune disorder characterized by a combination of arterial or venous thrombosis and recurrent fetal loss accompanied by elevated titers of antiphospholipid antibodies. Catastrophic APS is a small subset of APS, characterized by widespread systemic thrombotic disease with multiorgan failure. The diagnosis of catastrophic APS may be difficult, predominantly due to its frequently atypical presentation. In the present work, we describe a case of a 68-year-old male who presented with cerebral infarction, disseminated intravascular coagulation (DIC), and acute respiratory distress syndrome. The patient was successfully treated with anticoagulants, antibiotics, and steroid therapy. Physicians should be aware of the possibility of this syndrome as a cause of DIC with thrombotic disease because prompt recognition is essential for effective treatment.

A case of congenital adrenal hyperplasia presenting as adrenal incidentaloma / 대한내과학회지

Congenital adrenal hyperplasia, an autosomal recessive disorder resulting from an enzymatic defect during cortisol biosynthesis (i.e., 21-hydroxylase deficiency), is characterized by impaired production of cortisol with or without impaired production of aldosterone, chronic stimulation of the adrenal cortex by corticotropin, and overproduction of cortisol precursors and androgens. The severity of the hormonal abnormalities and clinical symptoms depend on the degree of enzymatic activity. Phenotypes are classified into the following types: the severe salt-wasting type, the simple virilizing type, and the non-classic type. Despite adequate treatment, patients may be at risk for salt-wasting adrenal crisis, precocious puberty, short stature, infertility, psychosocial problems, and tumor formation, including adrenal incidentaloma. Here we present a case of adrenal incidentaloma in a 14-year-old boy who was eventually diagnosed with congenital adrenal hyperplasia due to a 21-hydroxylase deficiency. The patient had a history of salt-wasting adrenal crisis, but survived without continuous glucocorticoid and mineralocorticoid treatment. Note also that both plasma aldosterone and plasma renin activity were elevated in this case.

Saline Versus Nafamostat Mesilate Anticoagulation for Continuous Veno-venous Hemofiltration (CVVH) in Patients at High Risk of Bleeding: A Prospective Study / 대한신장학회지

PURPOSE:In patients with a higherrisk of bleeding, performing CVVH with heparin or saline anticoagulation is associated with increased bleeding or thrombotic risk. Nafamostat mesilate (NM), a serine proteinase inhibitor, while inhibiting various clotting factors in filter circuit, is characterized by short half life resulting in little systemic anticoagulation effect. Accordingly, we prospectively evaluated the anticoagulant effect and safety of NM in patients with a higher risk of bleeding who underwent CVVH. METHODS:Among 43 patients with high risk of bleeding [defined by (1) INR>2, aPTT>20 sec, platelet2, aPTT>20 sec, platelet<50,000/mm3), the positive effect of NM on circuit lifespan persisted irrespective of the coagulation status. CONCLUSION:As compared with saline bolus, nafamostat mesilate infusion was associated with higher CVVH filter life. In patients with high risk of bleeding, nafamostat mesilate can be used as a safe and effective anticoagulant for CVVH with acceptable filter life

Sulodexide-induced Hyperkalemia: A Case Report / 대한신장학회지

Sulodexide is composed of two glycosaminoglycans (fast-moving heparin 80%, dermatan sulfate 20%) that are capable of preventing diabetic nephropathy by correcting abnormal glycosaminoglycan metabolism. Considering heparin-like propertyof sulodexide, side effect profiles of sulodexide are expected to be similar with those of heparin. Among those side effects, we remarked on heparin-induced hyperkalemia and hereby report a case of severe hyperkalemia during the use of sulodexide. A 52-year-old man with diabetic nephroapthy and hypertension was admitted to our hospital because of severe hyperkalemia up to 7.5 meq/L. His clinical condition was stable and medications including losartan and furosemide had not been changed for last 6 months except the addition of sulodexide, which was started 30 days prior to admission. Despite intensive use of Kayexalate and immediate discontinuation of losartan, hyperkalemia aggravated up to 8.0 meq/L. After recognition of possible sulodexide-induced hyperkalemia, sulodexide was discontinued, which resulted in rapid correction of hyperkalemia. In view of the above discussed clinical consideration, we suspect sulodexide as a major cause of hyperkalmia and report this case with a review of literature.

A case of fulminant hepatic failure due to cyproterone acetate in a patient with cryptogenic liver cirrhosis / 대한내과학회지

Cyproterone acetate is an antiandrogenic drug that has been used in prostatic cancer. The drug is thought to be well-tolerated but has hepatotoxic effects. An 89 year-old man treated with cyproterone acetate 300 mg/d for prostatic cancer presented with a hepatotoxic reaction. Toxic hepatitis was diagnosed and cyproterone acetate was stopped immediately. The patient was treated with supportive management and a corticosteroid, but he died 28 days after administration due to liver failure. A liver biopsy performed after his death revealed the presence of acute hepatitis with cirrhosis. Underlying cirrhosis was not suspected before his death. Ultimately, the case was diagnosed as fulminant hepatic failure due to cyproterone acetate with underlying cryptogenic liver cirrhosis. This case and current literature highlight the hepatotoxic potential of cyproterone acetate and illustrate the importance of clinical surveillance, especially in patients with unrecognized liver disease.