Vertebral fracture is associated with myocardial infarction in incident hemodialysis patients: a Korean nationwide population-based study.

Chronic kidney disease (CKD)-mineral and bone disorder suggests that fragile bone and vascular disorder might be connected closely in CKD patients. In this study, fracture event was significantly associated with myocardial infarction (MI) in end-stage renal disease patients on hemodialysis (HD), especially for vertebral fractures. INTRODUCTION: CKD-mineral and bone disorder is characterized by biochemical abnormalities, bone disorders, and vascular calcification. We aimed to verify the association between fracture and MI in CKD patients. METHODS: Records for incident CKD stage 3 to 5 patients and patients who initiated HD between July 2014 and June 2018 were retrieved from the Korean Health Insurance Review & Assessment Service Database. Fractures were defined using diagnostic codes and were classified into vertebral, femoral, and other site fractures. MI was defined using a combination of MI diagnostic codes and related procedure codes. Multiple logistic regressions and 1:1 propensity score matching analysis were conducted. RESULTS: A total of 38,935 patients (HD, 11,379; pre-dialysis CKD, 27,556) were included in this study. A total of 5,057 (13.0%) patients experienced fracture, and 1,431 (3.7%) patients had MI. Multiple logistic regression analysis showed that fracture was significantly associated with MI in the HD group (odds ratio (OR) 1.34, P = 0.024), but not in the pre-dialysis CKD group (OR 1.04, P = 0.701). After propensity score matching for age, gender, and diabetes mellitus between patients with and without fracture, fracture still significantly correlated with MI in HD patients (OR 1.47, P = 0.034) but not in patients with pre-dialysis CKD (OR 1.04, P = 0.751). Subgroup analysis by fracture site found that vertebral fracture was associated with MI in HD patients (OR 2.11, P = 0.024), but femoral or other site fractures were not. CONCLUSION: In HD patients, fracture was significantly associated with MI, especially for vertebral fractures patients.

Feasibility of hypomethylating agents followed by allogeneic hematopoietic cell transplantation in patients with myelodysplastic syndrome.

The role of hypomethylating agent therapy (HMT) as a bridge to allogeneic hematopoietic cell transplantation (alloHCT) in patients with myelodysplastic syndrome (MDS) remains undetermined. We investigated the feasibility of HMT followed by alloHCT in patients with MDS. In all, 19 patients who received HMT followed by alloHCT were analyzed. A total of 7 patients were classified as low-risk and 12 as high-risk, based on World Health Organization (WHO) classification at the time of HMT. HMT consisted of decitabine in 9 patients and azacitidine in 10. After HMT, two patients achieved CR, six mCR, three hematologic improvement alone, and six SD in terms of best response. HMT did not alter WHO classification in 15 patients (79%), whereas 1 patient (5%) improved and 3 (16%) progressed to AML. Most patients (95%) received a non-myeloablative conditioning regimen based on fludarabine/BU/anti-thymocyte globulin, and peripheral blood-mobilized stem cells. Neutrophil and platelet engraftments were achieved in 95 and 79% of patients, respectively. The incidences of acute and chronic GVHD were 42 and 26%, respectively. In all, 2-year OS rates were 68%, and the overall outcomes of those who achieved CR/mCR with HMT tended to be superior to those without CR/mCR. HMT followed by alloHCT was a feasible and effective treatment strategy for patients with MDS.

Bio-anaerobic treatability study for PCBs-contaminated oil.

This study investigated the bio-treatability of PCB contaminated oil for the development of design and operational parameters for the bioreactor. Input of external carbon and nutrient source in the aqueous phase was found to be required for the treatment of polychlorinated biphenyls (PCBs)-contaminated oil. Addition of surfactant was investigated for the emulsification of oil to reduce interference of contact with microorganisms and PCBs. The ratio of surfactant to oil was empirically optimized to 1 : 1. The higher PCB removal efficiency was obtained at 30 days of hydraulic retention time (HRT) in the semi-batch reactor study without cell recycle. The removal efficiency measured in mixed liquor was maintained at over 85% on average at 32 +/- 2 degrees C and 30% at 22 +/- 2 degrees C. More than 0.2 g/l/d of the organic loading rate was suggested to be maintained for various PCB loading rates (0.02-0.6 mg-PCB/l/d). For high biomass retaining and easy collection of treated oil, an Anaerobic Sequencing Batch Reactor (ASBR) was investigated. The removal of Aroclor was observed as more than 50% in the oil phase with 3 days reaction time and about 40% in overall phases, i.e. oil, liquid, biomass phases at 22 +/- 2 degrees C. US EPA verification results on the process performance are included in this presentation.

Treatment of intravenous immunoglobulin-resistant Kawasaki disease with methotrexate.

OBJECTIVE: To evaluate the effect of low-dose oral methotrexate (MTX) as treatment for patients with Kawasaki disease (KD) resistant to intravenous immunoglobulin (IVIG). METHODS: The subjects were four patients with KD, aged 8 months to 8 years old, who showed persistent disease after treatment with high-dose IVIG (2 g/kg) and aspirin (100 mg/kg). These patients were re-treated with IVIG and were also treated with IV dexamethasone (0.3 mg/kg). IV dexamethasone induced defervescence in three patients, but fever recurred upon discontinuing the steroid. One patient showed no response to either IVIG or dexamethasone. All patients were subsequently treated weekly with low-dose oral MTX [10 mg/body surface area (BSA)]. RESULTS: MTX treatment resulted in rapid defervescence, improvement in clinical symptoms, and normalization of acute-phase reactants in all patients. There was no progression of coronary artery dilatation and MTX was discontinued with no recurrence of fever. No adverse effects of MTX were observed. CONCLUSION: Low-dose oral MTX is an effective treatment for refractory KD.

Serum cytokine profiles in patients with Plasmodium vivax malaria: a comparison between those who presented with and without thrombocytopenia.

One of the peculiar features of Plasmodium vivax malaria in South Korea is the surprisingly high frequency of thrombocytopenia. The mechanism by which this malaria-related thrombocytopenia develops and its role in the pathology and progress of human infection with P. vivax have not yet been completely understood. In the present study, the serum cytokine profiles of cases of P. vivax malaria who presented with thrombocytopenia were compared with those of similar cases who did not have thrombocytopenia at presentation. The subjects were the 94 consecutive cases of P. vivax malaria who presented at five hospitals in South Korea (all near the Demilitarized Zone) between May 2000 and October 2002, 47 of whom had thrombocytopenia at presentation. When mean values and (S.E.) were compared, the thrombocytopenic patients were found not only to be generally older than the non-thrombocytopenic [25.3 (1.1) v. 21.3 (0.18) years; P < 0.001] but also to have presented with higher serum concentrations of aspartate aminotransferase [77.6 (16.6) v. 32.3 (7.4) U/litre; P < 0.0001], alanine aminotransferase [96.7 (19.0) v. 44.7 (12.0) U/litre; P = 0.0001], interleukin-1 [49.9 (7.4) v. 23.7 (5.1) pg/ml; P < 0.001], interleukin-6 [174.9 (26.4) v. 57.3 (14.6) pg/ml; P = 0.001], interleukin-10 [308.2 (39.6) v. 137.9 (23.1) pg/ml; P < 0.002] and transforming growth factor-beta [1134.3 (387.5) v. 416.6 (183.8) pg/ml; P < 0.0001], and higher levels of parasitaemia [4345.7 (966.6) v. 1443.8 (222.7) parasites/microl; P = 0.03). The non-thrombocytopenic patients, however, had relatively high total leucocyte counts [5.8 (0.24) v. 5.4 (0.66) leucocytes/nl; P = 0.03]. The thrombocytopenia associated with P. vivax malaria in South Korea therefore appears to be associated with elevated serum concentrations of both pro- and anti-inflammatory cytokines. To define the role of each cytokine in the development of thrombocytopenia during the course of acute P. vivax malaria, further prospective studies are needed.

Raised serum interleukin 15 levels in Kawasaki disease.

BACKGROUND: Interleukin (IL)15 is a novel cytokine that induces T cell proliferation, B cell maturation, natural killer cell cytotoxicity, and may have a pivotal role in the pathogenesis of inflammatory disease, acting upstream from tumour necrosis factor alpha (TNFalpha). Kawasaki disease (KD) is an inflammatory disease, in which serum levels of inflammatory cytokines such as TNFalpha and IL6 are increased. OBJECTIVE: To examine the serum levels of IL15 in KD and to evaluate the role of IL15 in estimating the severity of inflammation in KD. RESULTS AND CONCLUSION: There was a significant increase in the mean (SD) serum levels of IL15 measured in the acute stage of KD (11.5 (5.8) pg/ml) compared with those in the subacute stage (1.3 (0.9) pg/ml) (p<0.01) and normal controls (0.9 (1.0) pg/ml) (p<0.01). The increase in IL15 correlated with the increase in TNFalpha (r(s)=0.66, p<0.01); however it did not correlate with the levels of erythrocyte sedimentation rate and C reactive protein, suggesting that IL15 may not be a useful marker in estimating the severity of inflammation in KD.

[Development of gerontological nursing curriculum model].

PURPOSE: This study was conducted to develop gerontological curriculum model which reflects the need of Korean society. METHOD: Three round Delphi survey method was applied to find consensus of gerontological nursing competencies (knowledge, attitudes and skills) for graduates of nursing schools from the panel of gerontological nursing practice experts. Important concepts in gerontological nursing were delineated from literature review and discussions of gerontological nursing educators. Based on these results the gerontological nursing curriculum model was developed and course structure outlined by the researchers as a group. RESULT: As the result of delphi survey, 32 items of knowledge, 29 items of attitude, and 21 items of skill were identified. The curriculum model constructed around a cube with three plane- functional capacity levels, settings, and nursing practice. Specific knowledge, attitudes and skills for gerontological theory and practicum course were suggested. Competency items were assigned to theory and/or practice. CONCLUSION: A curriculum model for gerontological nursing has been developed by a group of gerontological nursing educators. The curriculum model should be further tested and developed with detailed theory and practicum course outline and textbooks.

Immune response induced by immunization with Hepatitis B virus core DNA isolated from chronic active hepatitis patients.

There are many mutations in the gene encoding Hepatitis B virus (HBV) core antigen of chronic active hepatitis patients, and such mutations are most likely to be related to the severity of disease. Here, we constructed plasmids containing wild-type and deletion type of HBV core gene (HBc) to develop an experimental DNA vaccine and to compare immunogenicity of two types of HBc vaccine. Twenty-nine wild-types and seven deletion types of HBc were detected in sera of 32 Korean patients with chronic active hepatitis. Four wild-types (W1, W2, W4, W6) and two deletion types (D3, D4) of HBc were cloned into the pcDNA3 vector. Intramuscular immunization with wild-type HBc efficiently increased serum anti-HBc antibody response in a dose-dependent manner. Anti-HBc antibody response in mice injected with W6 increased 14 days after immunization, and peaked after 30 days and was maintained at least up to 50 days. W6 immunization induced a specific cytotoxic T lymphocyte response to W6-transfected 3LL (3LL-W6), and reduced the sizes of tumor mass of mice challenged with 3LL-W6 or 3LL transfected with D4. However, intramuscular immunization with D3 and D4 did not show antibody response at all. D3 and D4 have 157 bp (from 331 to 491 bp) and 122 bp (from 327 to 448 bp) gene deletion, respectively, and these encode class II MHC-restricted T-cell epitope. Altogether, these results suggest that mutant virus that has deleted HBc gene may evade immune systems due to loss of T-cell epitope.

DNA-mediated immunization of mice with plasmid encoding HBs antigen.

In order to develop an experimental DNA vaccine for the prevention and treatment of hepatitis B virus infection, hepatitis B virus surface antigen (HBsAg) DNA was subcloned into an E. coli-eukaryotic cell shuttle vector and was expressed in the Baculovirus expression system. Intramuscular, intradermal, and intraperitoneal injections of 30 microg of the plasmid DNA expressing HBsAg induced humoral and cellular immune responses in ICR mice. The first IgG antibodies were detected after ten days and specific IgG antibody titers peaked after two months of a single intramuscular DNA injection. Anti-HBs antibody titers gradually increased and peaked at four months following intradermal DNA injection, and in case of intraperitoneal injection they peaked at seven months. Generation of HBs-specific helper T lymphocytes was also investigated through the production of interleukin-2 by T helper cells. Boosting effects of HBs DNA were investigated without much results. In general, DNA-mediated HBs immunization induced humoral and cellular immune responses in mice that appears to simulate immune responses in human during the course of HBV vaccination.

Combined cis-platinum and alpha interferon therapy of advanced hepatocellular carcinoma.

To evaluate the clinical efficacy of alpha-interferon(IFN-alpha) plus cis-platinum in hepatocellular carcinoma(HCC). 56 inoperable patients with HCC were divided into IFN-alpha plus cis-platinum treated group (n = 30) and no antitumor therapy group (n = 26). The survival of IFN-alpha plus cis-platinum treated patients was significantly better than that of patients who received no antitumor therapy (p = 0.001). Median survival time was 33 weeks and 14.0 weeks, respectively. The cumulative estimated survival rates of our IFN-alpha plus cis-platinum treated group (93.5% at 3mo, 75.0% at 6mo) were for longer than that of the no antitumor therapy group (84.6% at 3mo, 57.7% at 6mo). Objective tumor regression, greater than 50% was observed in 13.3% (4 of 30) of patients receiving IFN-alpha plus cis-platinum. By the univariate analysis, the absence of portal vein thrombus (p < 0.05), alkaline phosphatase lesser than 280 U/L (p = 0.001), total bilirubin less than 2.0 mg% (p < 0.05), serum triglyceride less than 155 mg/dl (p < 0.05) were shown to be the factors most significantly favoring a better survival. By the multivariate analysis, using Cox proportional hazards model, IFN-alpha plus cis-platinum treated group (p = 0.0001), alkaline phosphatase less than 280 mg/dl (p = 0.005), the absence of portal vein thrombus (p = 0.020) were independent favorable prognostic factors. We conclude that IFN-alpha plus cis-platinum is useful in patients with inoperable HCC and the above favorable prognostic factors may also be useful in the design and analysis of future clinical trials of systemic chemotherapy for HCC.

A comparison of the relaxation responses of isolated cavernosal smooth muscles by endothelium-independent and endothelium-dependent vasodilators in diabetic men with impotence.

This study was intended to explore the effects of endothelium-independent, direct smooth muscle relaxants(papaverine, verapamil) and endothelium-dependent vasodilators(acetylcholine, bradykinin, adenosine) on the isolated cavernosal smooth muscle strips taken from diabetic men with impotence. When smooth muscle contraction was evoked with norepinephrine for the study of relaxation to these vasodilators, the tension induced was similar in diabetic and non-diabetic men with importance. Papaverine showed the strongest relaxation response followed by verapamil, acetylcholine, bradykinin and adenosine both in non-diabetic and in diabetic men. Relaxation of the cavernosal tissues to endothelium-independent vasodilators was similar in non-diabetic and diabetic men. However, the relaxation response of the tissues to endothelium-dependent vasodilators was significantly reduced in the diabetic group compared with that in the non-diabetic group (p < 0.05). In conclusion, the impairment of endothelium-mediated relaxation of cavernosal smooth muscle seems to play a more important role in the pathogenesis of diabetogenic impotence rather than the problem of smooth muscle itself. This finding forms a rational basis for the use of intracavernosal injections of vasodilators to induce endothelium-independent relaxation of the cavernosal smooth muscle in the patients with diabetogenic impotence.

Prevalence of hepatitis C antibody in patients with chronic liver disease and hepatocellular carcinoma in Korea.

To investigate the contribution of hepatitis C virus (HCV) to chronic liver disease and hepatocellular carcinoma (HCC) in Korea, antibodies to HCV (anti-HCV) were tested by enzyme immunoassay in 1759 patients with chronic liver disease and HCC, and in 808 healthy adults. The prevalence of anti-HCV was 1.6% in 808 controls. Anti-HCV was present in 32 (7.7%) of 418 hepatitis B surface antigen (HBsAg)-positive and 128 (53.1%) of 241 HBsAg-negative patients with chronic hepatitis, 16 (6.0%) of 265 HBsAg-positive and 90 (30.5%) of 295 HBsAg-negative patients with liver cirrhosis, and 16 (4.8%) of 330 HBsAg-positive and 61 (29.0%) of 210 HBsAg-negative patients with HCC. Antibodies to hepatitis B core antigen (anti-HBc) were present in 80-88% of patients who were seropositive for anti-HCV and seronegative for HBsAg. Among the sera from 114 patients with HBsAg-negative and anti-HCV-positive chronic liver diseases, HBV DNA and HCV RNA were detected by polymerase chain reaction (PCR) in 54 (47.4%) and 61 (53.3%), respectively. Both HBV DNA and HCV RNA were detected in 4 (4.4%) samples. The mean age of the patients with both HBsAg and anti-HCV was not different from that of patients who were seropositive for HBsAg alone. These findings indicate that current and/or past HBV infection is still the main cause of chronic liver disease in Korea.(ABSTRACT TRUNCATED AT 250 WORDS)

Bilateral fractures of Hydroflex penile prostheses: an unusual complication.

We report bilaterally fractured Hydroflex implants in 2 patients. One fracture was complete and three were incomplete. All the fractures occurred at the junction of the rear reservoir and the inflation chamber.

Clinical application of posterior calf fascio-cutaneous pedicle flap in leprosy foot ulcer.

Lower extremities of the leprosy patients are characterized by the decreased sensation of the foot from peripheral nerve damage. As a result, repetitive foot ulcers are frequently seen. When these repetitive shallow ulcers become infected, they result in deep soft tissue ulcers and even osteomyelitis. The treatment of these ulcers in leprosy is a challenging problem both to the patient himself and to medical personnel. Conventional treatment methods for these ulcers include, according to the wound condition, skin graft, local flap, long-term cast immobilization, wedge resection of the joint and even amputation in severe cases. But all these methods have the disadvantages of frequent recurrences, long hospitalization periods and permanent foot deformities. Recently in Korea, despite the decreased occurrences of new patients and the decreased frequencies of facial and hand deformity formation due to the active early diagnosis and treatment, there still exists a large number of foot deformities resulting from decreased foot sensation. Moreover, treatment modalities are not definitely established. In fact, there are many environmental difficulties in applying the free flap transfer to the foot ulcer of leprosy patients in leprosy sanatorium as opposed to treating the non-leprosy patients. And so, from 1990 to 1993, we performed 6 superior-based posterior calf cross leg flap transfers and 1 distal-based flap transfer, under spinal anesthesia, referred by the leprosy sanatorium for deep foot ulcers. We obtained favorable results in 6 patients and partial necrosis in a patient who received distal based flap transfer.

Direct measurement by pulsed-field gel electrophoresis of induction and rejoining of X-ray-induced double-strand breaks in cultured mouse cells.

The induction and rejoining of X-ray-induced double-strand breaks (dsb) in chromosomal DNA has been difficult to measure. We have developed a pulsed-field gel electrophoresis (PFGE)-based system for directly estimating DNA sizes between 0.2 and 10 million base pairs. With this system we can estimate average DNA sizes from randomly broken chromosomes by measuring the approximate molecular weight of the maximum DNA concentration. In practice this is effective where the average is between 1 and 4 million bp allowing both shoulders of the distribution to be observed. This corresponds to a dose range of 20-80 Gy. Qualitative differences from non-irradiated DNA can be observed down to about 5 Gy. We have confirmed the dose response by utilizing methotrexate-resistant mouse cells containing circular double-minute (dm) chromosomes of 1, 1.5, and 3 million bp. The kinetics of dsb rejoining from doses of 50 and 5 Gy was investigated: 50 Gy reduced the chromosomal DNA to an average size of approximately 1 million bp, followed by a constant repair rate of 44 dsb per minute per cell for 3 h (assuming a total genome size of 10 million bp).

Effects of allopurinol on smoke inhalation in the ovine model.

We hypothesized that the pulmonary damage induced by smoke inhalation is the result of ischemic reperfusion injury. We determined the effect of allopurinol (xanthine oxidase inhibitor) on the pulmonary microvascular fluid flux in an ovine model after inhalation of cotton smoke (n = 13) and compared these data with those from untreated similarly smoke-injured (n = 7), as well as sham- (air, n = 9) smoked, animals and sheep given an equivalent dose of CO (n = 7). Smoke injury resulted in an increased lung lymph flow, lymph-to-plasma protein ratio, lung content of polymorphonuclear cells, and extravascular lung water (gravametric), in addition to histological evidence of tissue (pulmonary) edema and destruction. No significant difference was found in these variables between the sheep that were injured with smoke whether or not they were pretreated with allopurinol. The sham-smoked and CO-insufflated animals showed no significant changes in cardiopulmonary function or morphology. We conclude that there are few data to support a role of ischemic reperfusion injury in the pulmonary damage seen after smoke inhalation.