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Abstract

Y.F. Xia, S. Huang, X. Li, N. Yang, J. Huang, C. Xue, M. Zhang, J.C.K. Leung, M.F. Lam and J. Li

¹Department of Nephrology, First Affiliated Hospital, ²Department of Medical Genetics, ³Department of Medical Statistics, Zhongshan Medical College, Sun Yat-Sen University, Guangzhou, ⁴Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong, China
Aims: To investigate the association of megsin A23167G polymorphism with susceptibility and progression of IgA nephropathy in Chinese population. Methods: 435 IgA nephropathy patients and their family members were recruited for a family-based association study. Genotypes of megsin A23167G were determined by direct sequencing. The results were analyzed by transmission disequilibrium test (TDT) and haplotype relative risk (HRR). Clinical data and histological scores of renal lesions were compared between patients with different genotypes. According to disease stability, IgA nephropathy patients were divided into progressive group and stable group. The distribution of genotype frequencies were compared between the 2 groups. Results: TDT revealed that megsin 23167G alleles were transmitted more frequently from heterozygous parents to patients than expected (classical TDT: c2 = 5.435, p = 0.020, extended TDT: c2 = 5.017, p = 0.025). HRR analyses showed significant differences between transmitted and nontransmitted allele frequencies (c2 = 7.006, p = 0.008, HRR = 1.762). The scores of glomerular index and glomerular sclerosis index were higher in GG genotype patients than those in other genotypes (F = 4.570, p = 0.033, F = 4.324, p = 0.038, respectively). The distribution frequency of GG genotype in the progressive group was higher than that of the stable group (c2 = 4.370, p = 0.037). No statistical difference was found in tubulo-interstitial index, vascular index and clinical characteristics between the 2 groups. Conclusion: The polymorphism of megsin A23167G is associated with susceptibility and progression of IgA nephropathy in Chinese population. GG genotype is associated with severe histological lesions and progression of the disease.Correspondence to:
Prof. J. Li
Department of Nephrology
First Affiliated Hospital
Sun Yat-sen Universtiy
74 Zhongshan Road II
Guangzhou 510080, PR China
Email: [email protected]

Abstract

E.J. Hoorn, J. Lindemans and R. Zietse

¹Department of Internal Medicine, ²Department of Clinical Chemistry, Erasmus Medical Center, Rotterdam, The Netherlands
Background: Although hyponatremia with concomitant renal dysfunction has been described anecdotally, little is known about how these two conditions are related, which type of renal dysfunction usually occurs, and which patients are at risk. Methods: From 3,029 measured serum sodium (SNa) concentrations in 3 months, patients with at least one SNa £ 125 mmol/l were selected, and divided in patients with at least 1 SCreat ³ 125 mmol/l (study group, n = 20), and patients whose SCreat remained normal (control group, n = 50). Results: During the first 5 days of hospitalization, SCreat almost doubled in the study group from 125 ± 40 mmol/l to 207 ± 72 mmol/l, while SNa decreased concurrently from 130 ± 2 mmol/l to 122 ± 3 mmol/l. The peak SCreat and SNa values coincided, and the average courses were highly correlated (r = 0.88, p < 0.001). The study group more often had heart failure (10/20 vs. 1/50, p < 0.001) and liver failure (7/20 vs. 4/50, p = 0.009), and received more often loop diuretics (13/20 vs. 12/50, p = 0.002), spironolactone (11/20 vs. 7/50, p = 0.001), and/or angiotensin-converting enzyme inhibitors (5/20 vs. 2/50, p = 0.02). Four patients were admitted to the intensive care (10 in control group, p = 1.0), and 5 patients died (10 in control group, p = 0.7). Conclusions: Renal dysfunction is common in severe hyponatremia and usually develops in an acute-on-chronic fashion with concomitant deterioration of both conditions. This concourse is associated with heart failure, liver failure, and/or a renal drug regimen. Given the recent results of clinical trials, this patient group may be especially suitable for treatment with vasopressin antagonists.Correspondence to:
E.J. Hoorn, MD
Erasmus Medical Center
Dialysis Unit, Room Bd 391
Dr. Molewaterplein 40
3015 GD Rotterdam, The Netherlands
Email: [email protected]

Abstract

J. Liesker, A.-M. van Elsacker-Niele, R. Blanken and C. Halma

Department of Internal Medicine, Medical Center Leeuwarden, ²Department of Medical Microbiology, Public Health Laboratory, ³Department of Dermatology, Medical Center Leeuwarden, The Netherlands
A 30-year-old patient treated with CCPD presented with genital ulcers and a culture-negative peritonitis. Herpes simplex virus type 2 (HSV-2) was cultured from the effluent and the genital lesions. Primary HSV-2 infection was diagnosed by serology. This is the first documented case of PD peritonitis caused by HSV-2. We speculate that cases of culture-negative PD peritonitis may be due to recurrences of genital herpes.Correspondence to:
C. Halma MD, PhD PO Box 888 8901 BR Leeuwarden, The Netherlands
Email: [email protected]

Abstract

J.J. Lima, B. Nhi Beasley, R.B. Parker and J.A. Johnson

¹Center for Clinical Pediatric Pharmacology & Pharmacogenetics, Nemours Children?s Clinic, Jacksonville, FL, ²University of Tennessee College of Pharmacy, Memphis, TN, ³Food and Drug Administration, Center for Drug Evaluation and Research, Rockville, MD,
Objective: To formulate and evaluate a pharmacodynamic model that characterizes the effects of S-verapamil on the circadian 24-hour ambulatory blood pressure (ABP). Methods: ABP was recorded in 19 hypertensive patients off drug, and following administration of the targeted dose of COER-V given once daily for at least 30 days. Blood samples were collected after the last dose for determination of the pharmacokinetic of S-verapamil. ABP vs. time was analyzed using a cosinor function, and the effects of S-verapamil on ABP were fitted using the pharmacodynamic model. Results: COER-V decreased average systolic and diastolic blood pressures (mesors): baseline, 142 Correspondence to:
J.J. Lima, Pharm. D. Center for Clinical Pediatric Pharmacology & Pharmacogenetics Nemours Children?s Clinic 807 Nira Street Jacksonville, FL 32207, USA
Email: [email protected]

Abstract

A.L.F. Chan, H.J. Hsieh, Y.-A. Hsieh and S.-J. Lin

¹Department of Pharmacy, Chi Mei Medical Center, Tainan, Taiwan and ²Graduate Institute of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan
Objective: To report a fatal case of amiodarone-induced acute hepatotoxicity after intravenous amiodarone administration and similar fatal cases review. Case summary: A 72-year-old woman with a history of hypertension, prior cardiovascular disease, atrial fibrillation and diabetes mellitus was admitted to the hospital with acute pyelonephritis and transferred to the intensive care unit due to cerebral infarction. An antidiabetic drug, a low dose of aspirin and intravenous amiodarone therapy was started. After receiving a second dose of amiodarone (1,200 mg; injection rate 1 mg/min), the woman developed ascites, jaundice, high levels of serum transaminases, decreased prothrombin time, and finally became unconscious. Immediately after treatment was discontinued, her extremely high hepatic parameters returned to normal. According to the Naranjo probability scale, this adverse reaction was highly probable. Discussion: The occurrence of acute liver damage after intravenous amiodarone is rare but harmful. It can be induced by polysorbate 80, a solubilizer, by immunomediated centrilobular necrosis, or by the presence of a functional PPAR-α gene. Conclusion: Amiodarone is an effective antiarrhythmic agent for preventing and treating atrial and ventricular arrhythmias. The molecular mechanism causing acute hepatic damage after amiodarone treatment is not clear. Therefore, amiodarone must be administered with care, and liver function should be monitored closely in patients treated with this drug.Correspondence to:
Dr. S.-J. Lin, Graduate Institute of Pharmacy, Kaohsiung Medical University, 100 Shi-Chuan 1st Rd, Kaohsiung, Taiwan
Email: [email protected]

Abstract

S. Krause, T. Göhringer, M.C. Walter, B.G.H. Schoser, P. Reilich, J. Linn, G.E. Pöpperl, L. Frölich, F. Hentschel, H. Lochmüller and A. Danek

¹Neurologische Klinik and ²Friedrich-Baur-Institut, ³Abteilung für Neuroradiologie am Institut für Diagnostische Radiologie, and ⁴Klinik für Nuklearmedizin, Ludwig-Maximilians-Universität München, ⁵Abteilung für Gerontopsychiatrie and ⁶Abteilung für Neuroradiologie, Zentralinstitut für Seelische Gesundheit Mannheim, Ruprecht-Karls-Universität Heidelberg, Germany
Inclusion body myopathy with Paget disease of bone and frontotemporal dementia (IBMPFD, MIM 167320) is a recently identified autosomal dominant disorder due to mutations in the valosin-containing protein (VCP) that affects muscle, bone and brain. Brain involvement and neuropsychological findings of IBMPFD have not been described in detail. A patient carried a novel heterozygous base pair change, 47832C>T, in the VCP gene that resulted in substitution of an arginine residue by cysteine at position 93 (R93C). He presented first with myopathy while bone involvement remained subclinical. The patient developed behavioral abnormalities in his 60s and showed frank personality change with fluent empty speech at the age of 74 years. This syndrome was best classified as semantic dementia. Magnetic resonance imaging disclosed slight but progressive cerebral atrophy with prominent callosal and frontal white matter loss. Positron emission tomography demonstrated glucose hypometabolism of the frontal and temporal lobes disproportionate to their structural involvement. This first comprehensive clinical and neuroimaging study in IBMPFD may raise the awareness among clinicians as well as basic scientists for this exemplary genetic model of dementia.Correspondence to:
Prof. A. Danek; Neurologische Klinik, LMU, PF 701260,
81377 München,Germany
Email: [email protected]

Abstract

Y. Wu, X. Wang, X. Mo, Z. Xi¹, F. Xiao, J. Li, X. Zhu, G. Luan, Y. Wang, Y. Li and J. Zhang

¹Department of Neurology, The First Affiliated Hospital, Chongqing Medical University, Chongqing, ²Neurology Department of the First Affiliated Hospital, Guangxi Medical University, Nanning, ³Beijing Tiantan Hospital of the Capital University of Medical Sciences, ⁴Beijing Xuanwu Hospital of the Capital University of Medical Sciences, Beijing, China
Objective: To investigate the expression of monocyte chemoattractant protein-1 (MCP-1) in the brain tissue of patients with intractable epilepsy (IE) and to explore its role in the pathogenesis of IE. Material: Patients with IE were collected from the Department of Neurosurgery of several Chinese hospitals between 2002 and 2005. The average age of these 40 patients was 23.65 ± 10.14 (X ± SD) years (11 – 58 years), with 19 males and 21 females. In addition to the typical symptoms and distinct EEG features of epilepsy, all recruited patients met the requirements of intractable epilepsy. Methods: On the basis of positive results obtained from gene chip analysis, the expression of MCP-1 was first investigated in the brain tissue of IE patients (40 cases) using Western Blotting and immunohistochemistry and then compared with the controls. Results: Gene chip scanning demonstrated that expression of MCP-1 mRNA was upregulated in the brain tissue of patients with IE. Western Blotting and immunohistochemical experiments further confirmed that, as compared with that in the control group, expression of MCP-1 protein was significantly increased in the IE patients (p < 0.05). Conclusion: These results suggest that MCP-1 are involved in the pathogenesis of IE.Correspondence to:
Dr. X. Wang; Department of Neurology, The First Affiliated Hospital, Chongqing Medical University, Chongqing 400016, China
Email: [email protected]

Abstract

S.F. Bao^¹, L. Zhao^¹, Y.J. Liu^², T. Cong^¹, Z.J. Cheng^¹, Z. Li^¹ and H. Tian^³

^¹Trace Element Research Laboratory, ^²Department of Orthopedics, ³⁰¹ Hospital, Beijing, and ^³Pharmaceutical Factory, Harbin, P.R. China
Material and methods: One hundred and sixty growing chickens aged 70 days were fed in 32 cages, 5 each. The fracture with 1 – 2 mm defects at bilateral radius of wings was created by osteotomies. The chickens were then divided into 4 groups, 40 each. Every morning, the first group chickens as the control, were fed orally with 0.8% Na-CMC solution (sodium carboxymethyl cellulose), the other 3 groups with copper Na-CMC suspension (copper powder suspended in 0.8% Na-CMC) of different doses: 20, 40 and 80 mg Cu/kg body weight. All the chickens had free access to water and diet containing Cu 5.4 mg/kg diet. Ten chickens of each group were sacrificed at the 14th, 21st, 28th and 35th day postoperatively. Liver was taken for analysis of Cu and Zn content. Both radii were removed by dissection. Computed tomography scan (CT) was performed for measuring gray values of callus quantitatively. The biomechanical properties of the healing radius were analyzed by a 3-point bending test. Afterwards, the contents of calcium, magnesium, phosphorus, copper, zinc, iron and hydroxyproline in callus were determined. Results: The gray values of callus increased along with the increase of copper dose and the observing duration. At the 21st and 35th day after operation, the gray values of callus in the high-Cu group were significantly higher than that in the control, respectively (909 ± 220 vs. 597 ± 155; 973 ± 100 vs. 763 ± 179 HU p < 0.05). The calcium and magnesium in callus 35 days post operation were found to be much higher in middle and high Cu groups than that in the control, respectively (Ca: 177 ± 26.7, 176 ± 20.5 vs. 137 ± 34.7 mg/g; Mg: 2.98 ± 0.57, 3.06 ± 0.46, vs. 2.43 ± 0.53 mg/g; p < 0.05). The contents of hydroxyproline in callus 35 days post operation in high-Cu group were significantly higher than that in the control: 34.23 ± 1.96 vs. 32.17 ± 1.93 mg/g, p < 0.05. The biomechanical properties of repaired radius had the same tendency. Conclusion: Copper is helpful in fracture healing. However, the mechanism of the effect of copper on fracture healing is still to be further identified.

Abstract

X. Cui¹, L.J. Liu², P. Liu¹ and J. Sun¹

¹Institute of Chemistry and Microbacteria Detection, College of Public Health, West Part of Shandong University, and ²Institute of Inorganic Chemistry, College of Pharmacy, West Part of Shandong University, Jinan, PR China
Absorption, distribution and elimination of both microcrystalline cisplatin and routine cisplatin in mice by oral administration were studied. Concentrations of cisplatin in blood, liver, stomach and kidney of mice were determined by graphite furnace atomic spectrophotometry. After oral administration of microcrystalline cisplatin, cisplatin could reach peak concentrations in stomach, blood, kidney and liver at about 30 min. The stomach had the highest cisplatin level of all determined tissues, and remained high (> 3.42 mg/g) within a duration of 1 h. Compared with the ordinary cisplatin drug, the microcrystalline cisplatin has a higher peak concentration, indicating that microcrystalline cisplatin can be absorbed effectively. Kidney had a higher peak concentration of cisplatin at approximately 45 min than both liver and blood, and the elimination rate remained slow for 4 h. Thus, microcrystalline cisplatin would be a potential orally taken anti-gastric carcinoma drug, but its kidney toxicity should not be neglected.

Abstract

X. Cui¹, J. Sun¹, X.Y. Ling², C.F. Zhao², Z.J. Liu¹ and G.F. Xu²

¹Institute of Chemistry and Bacteria Detection, College of Public Health, West Campus of Shandong University, and ²Institute of Food and Nutrition, College of Public Health, West Campus of Shandong University, Jinan, PR China
The zinc fractional absorption of Chinese children in the rural region in Shandong province was studied under the routine dietary model. The volunteers, aged 4.7 ~ 6.3 years, 5 males and 5 females, were recruited from Shandong rural region. Stable 67Zn was used as tracer to label ZnCl2, and Yb was used as a marker of 67Zn recovery. 67ZnCl2 solution and Yb were added to a biscuit, and then administered to volunteers orally. The food and feces samples of all subjects were collected for 12 consecutive days. AAS and TIMS were used for determination of total zinc and stable zinc isotope ratio in food and feces samples, and the zinc fractional absorption was calculated. The daily intakes of iron, protein, fat, ascorbic acid, phytic acid and fibre were determined by AAS or traditional chemical analysis method and compared with RNIs. Results: The results showed that the fractional absorption of zinc is 12.94 ± 3.32%, much lower than that reported in the West. The daily intake of zinc is 11.16 mg, that is 96.67% of RNI, and the intakes of protein and ascorbic acid are only 56.73 and 19.00% of RNIs, respectively. Conclusions: Under the dietary model of Shandong rural region, although the daily intake of zinc has been close to RNI, the children have low zinc fractional absorption. The low intakes of ascorbic acid and protein may play an important role in reducing the zinc availability.Correspondence to:
Prof. X. Cui
Institute of Chemistry and Bacteria Detection
College of Public Health
West Campus of Shandong University
Jinan 250012, China
Email: [email protected]

Abstract

X. Cui¹, J. Sun¹, X.Y. Ling², C.F. Zhao², Z.J. Liu¹ and G.F. Xu²

¹Institute of Chemistry and Bacteria Detection, ²Institute of Food and Nutrition, College of Public Health, West Campus of Shandong University, Jinan, PR China
Objective: The objective was to predict the bioavailability of iron in children aged 4- to 6- years from Chinese traditional diets consumed commonly in Shandong rural region on the basis of the contents of nutritional factors known to promote or inhibit food iron absorption. Materials and methods: Iron absorption measurement from Chinese traditional diets was made in 10 subjects by using iron-stable isotope 57Fe, as tracer to label FeSO4. 57Fe and Dy were added to a biscuit, and administered orally 3 times a day for 2 days. The diet and feces samples were collected for 10 consecutive days after the intake of 57Fe. Atomic absorption spectrophotometer (AAS) and thermal ionization mass spectrometers (TIMS) were used for the determination of iron, calcium and stable iron isotope. The daily intake of ascorbic acid, fat, phytic acid and fiber was determined by biochemical analysis. Results: The absorption of iron was 6.06 ± 2.24%, much lower than the 10% reported in the West, which was adopted by Chinese authority to revise Chinese Recommended Dietary Allowance (RDAs) in 1988. The daily intake of iron was 10.29 mg, which was 85.8% of Chinese “Reference Nutrient Intakes (RNIs)” in 1998. The intakes of protein and ascorbic acid were only 56.70 and 19.00% of RNIs, respectively. Conclusion: Under the actual dietary pattern of Shandong rural region, the iron uptake of children is low, due to poor iron absorption and the insufficient daily iron intake.Correspondence to:
Prof. X. Cui
Institute of Chemistry and Bacteria Detection
College of Public Health
West Campus of Shandong University
Jinan 250012, PR China
Email: [email protected]

Abstract

J. Lichey

Evangelische Lungenklinik (ELK), Berlin
Das klinische Bild der Lungenarterienembolie (Lungenembolie, Pulmonalembolie, LE) ist insgesamt uncharakteristisch. Aus diesem Grund wird bei über 50 % der Patienten eine akute LE nicht erkannt. Die Mortalität der nicht erkannten und damit nicht behandelten Lungenembolie ist hoch. Andererseits geht eine bei falsch-positiver Diagnose begonnene Antikoagulantien-Therapie mit dem Risiko einer unter Umständen erheblichen Blutung einher. Durch stufenweise Ausschluss-Algorithmen können aufwendige, invasive und kostenträchtige Untersuchungen reduziert werden. Die Kombination von klinischer Einschätzung mittels eines validierten Scores (Wells-Score) und der D-Dimer-Bestimmung ist die effektivste und kostengünstigste Initial-Strategie. Ist die klinische Wahrscheinlichkeit (Prä-Test-Wahrscheinlichkeit) für eine Lungenembolie niedrig und der Plasma-D-Dimer-Spiegel normal, beträgt der negative prädiktive Wert (Post-Test-Wahrscheinlichkeit) nahezu 100 %. Hiermit können 47 % der Patienten mit initialem Verdacht auf Lungenembolie ausgeschlossen werden. Ist diese Konstellation nicht gegeben, die klinische Wahrscheinlichkeit hoch und/oder finden sich erhöhte D-Dimer-Spiegel, können weitere 20 % ausgeschlossen werden, wenn ein nachfolgendes Lungenszintigramm oder thorakales Spiral-CT in Kombination mit der Beinvenen-Sonografie normal sind. Bezüglich des Thromboembolie-Risikos sind diese stufenweisen Algorithmen mit dem “Goldstandard” Pulmonalisangiografie gleichwertig (oberes 95 %-Konfidenz-Limit: im Bereich von 1,3 – 2,0 % vs. 2,1 %). Durch stufenweise Ausschlussdiagnostik kann so die Angiografierate von 29 % auf 1 % gesenkt werden.Correspondence to:
Prof. Dr. med. J. Lichey
Evangelische Lungenklinik (ELK)
Lindenberger Weg 27
D–13125 Berlin
Email: [email protected]

Abstract

J. Lichey

Evangelische Lungenklinik (ELK), Berlin
Das klinische Bild der Lungenarterienembolie (Lungenembolie, Pulmonalembolie, LE) ist insgesamt uncharakteristisch. Aus diesem Grund wird bei über 50 % der Patienten eine akute LE nicht erkannt. Die Mortalität der nicht erkannten und damit nicht behandelten Lungenembolie ist hoch. Andererseits geht eine bei falsch-positiver Diagnose begonnene Antikoagulantien-Therapie mit dem Risiko einer unter Umständen erheblichen Blutung einher. Durch stufenweise Ausschluss-Algorithmen können aufwendige, invasive und kostenträchtige Untersuchungen reduziert werden. Die Kombination von klinischer Einschätzung mittels eines validierten Scores (Wells-Score) und der D-Dimer-Bestimmung ist die effektivste und kostengünstigste Initial-Strategie. Ist die klinische Wahrscheinlichkeit (Prä-Test-Wahrscheinlichkeit) für eine Lungenembolie niedrig und der Plasma-D-Dimer-Spiegel normal, beträgt der negative prädiktive Wert (Post-Test-Wahrscheinlichkeit) nahezu 100 %. Hiermit können 47 % der Patienten mit initialem Verdacht auf Lungenembolie ausgeschlossen werden. Ist diese Konstellation nicht gegeben, die klinische Wahrscheinlichkeit hoch und/oder finden sich erhöhte D-Dimer-Spiegel, können weitere 20 % ausgeschlossen werden, wenn ein nachfolgendes Lungenszintigramm oder thorakales Spiral-CT in Kombination mit der Beinvenen-Sonografie normal sind. Bezüglich des Thromboembolie-Risikos sind diese stufenweisen Algorithmen mit dem “Goldstandard” Pulmonalisangiografie gleichwertig (oberes 95 %-Konfidenz-Limit: im Bereich von 1,3 – 2,0 % vs. 2,1 %). Durch stufenweise Ausschlussdiagnostik kann so die Angiografierate von 29 % auf 1 % gesenkt werden.Correspondence to:
Prof. Dr. med. J. Lichey
Evangelische Lungenklinik (ELK)
Lindenberger Weg 27
D–13125 Berlin
Email: [email protected]

Abstract

B.J. Lim¹, K.S. Suh¹, K.R. Na², K.W. Lee² and Y.T. Shin²

¹Department of Pathology, Lancer Research Institute and ²Department of Internal Medicine, Chungnam National University College of Medicine, Moonhwa-dong, Jung-gu, Daejeon, Korea
Superimposition of poststreptococcal glomerulonephritis (PSGN) on the course of IgA nephropathy (IgAN) is uncommon. A case of PSGN during IgA nephropathy is presented. A 30-year-old man who had alternating gross and microscopic hematuria for 7 months underwent a renal biopsy. The first renal biopsy revealed IgAN with mesangial deposits of IgA and C3. Two months later, the patient suffered generalized edema, proteinuria, hematuria, an increased ASO titer and a decreased C3 level. A second renal biopsy revealed diffuse endocapillary proliferative glomerulonephritis with epimembranous hump-like electron-dense deposits of C3, but the original mesangial IgA deposits had disappeared. A diagnosis of acute PSGN was indicated. Two months after the onset of acute nephritic syndrome, the patient remained asymptomatic, except for microscopic hematuria and proteinuria. Some cases with persistent proteinuria or hematuria after PSGN are probably related to preexisting IgAN.Correspondence to:
K.S. Suh, MD
Chungnam National, University College of
Medicine, 6, Moonhwa-dong, Jung-gu, Daejeon, Korea
Email: [email protected]

Abstract

A.L. Chan¹,², H.-J. Hsieh² and S.-J. Lin¹

¹School of Pharmacy, Kaohsiung Medical University, Kaohsiung, and ²Department of Pharmacy, Chi-Mei Medical Center, Tainan, Taiwan
Objective: To assess the health and cost outcomes of pharmacist intervention versus non-intervention in activated protein C (drotrecogin alpha) therapy for patients with severe sepsis. Method: This is a retrospective study. We reviewed the medical records of patients aged 18 years and older who were admitted to our hospital for severe sepsis from January 1, 2003 to December 31, 2007. Only patients who are prescribed activated protein C for the treatment of severe sepsis according to the reimbursement criteria can be reimbursed by the Taiwan Bureau of National Health Insurance (BNHI). Our hospital stipulated that the criteria check list must be evaluated by a clinical pharmacist and the prescribing physician as to whether the patient is eligible to receive activated protein C. To assess the influence of pharmacist intervention on outcomes, we divided eligible patients into two groups, pharmacist-intervention group (Group A; n = 19) and non-pharmacist intervention group (Group B; n = 19). Both groups received a 96-h intravenous infusion of activated protein C at 24 µg/kg/h. We defined evident severe sepsis as concurrent antibiotic plus ventilator and/or vasopressor use. We compared group characteristics, 28-day in-hospital mortality, length of stay and direct medical costs between the two groups. One-way ANOVA was used for analysis. Results: 50% of patients in each group met the reimbursement criteria of the BNHI. Activated protein C therapy was initiated within 1.37 ± 0.4 days and 7.21 ± 7.8 days of admission to the ICU in Group A and Group B, respectively (p < 0.01). All of the patients in Group A (19/19) and 42.1% of the patients in Group B (8/19) received activated protein C within 12 – 48 h of admission to the Intensive care unit (ICU) (p < 0.01). 28-day mortality was lower for Group A than for Group B (26.7% and 43.8%, respectively). The length of stay in the ICU for patients in Group A was shorter than that in Group B (14.1 ± 7.7 vs. 19.7 ± 11.1, respectively; p < 0.079). Total direct medical costs for survivors in Group A were less than those in Group B (US$ 20,632.3 vs. US$ 24,785.8, respectively; p < 0.05). Conclusions: Pharmacist intervention in prescribing activated protein C for patients with severe sepsis might reduce direct medical costs and promote earlier initiation of therapy. The potential impact of pharmacist intervention on the timing of activated protein C therapy and the direct medical costs of treatment warrant further study.Correspondence to:
Dr. S.-J. Lin; School of Pharmacy, Kaohsiung Medical University, 100, Shi-Chuan 1st Rd., Kaohsiung, Taiwan
Email: [email protected]

Abstract

B.J. Lim, S.W. Hong and H.J. Jeong

Department of Pathology, Yonsei University College of Medicine, Seoul, Korea
Background: IgG nephropathy is one of the most recently described glomerulopathies, which frequently overlaps with C1q nephropathy. To clarify this entity, we evaluated renal biopsy cases with IgG deposits as a sole or predominant immunoglobulin. Methods: Fourteen cases demonstrating IgG as a predominantly deposited immunoglobulin in patients without infectious or autoimmune diseases between 1997 and 2008 were studied. Twelve patients had glomerular disease in the native kidney and the other 2 were renal allograft recipients. Results: Clinical presentation was microscopic hematuria, proteinuria, or both and nephrotic syndrome was observed in 3 patients. Segmental glomerulosclerosis was observed in 4 patients and mesangial hypercellularity was present in 7. Tubulointerstitial changes were not evident except for allograft biopsies. On immunofluorescence, mesangial or capillary wall IgG deposits were present in all cases, and C1q was observed in 11 cases in a similar pattern with IgG, co-dominant in 5 cases and dominant in 1. Conclusions: Since a significant overlap is frequently observed in these two rare conditions, we suggest a tentative diagnosis of IgG/C1q nephropathy in such cases.Correspondence to:
H.J. Jeong, MD
Department of Pathology, Yonsei University
College of Medicine
134 Shinchon-dong, Seodaemun-gu
Seoul 120-752, Korea
Email: [email protected]

Abstract

The effect of etanercept on suppression of the systemic inflammatory response in chronic hemodialysis patients

B.R. Don¹, K.Kim², J. Li², T. Dwyer¹, F. Alexander¹ and G.A. Kaysen¹,³,⁴

¹Division of Nephrology, University of California Davis School of Medicine and the UC Davis Medical Center, ²Division of Biostatistics, Department of Public Health Sciences, University of California Davis School of Medicine, ³Department of Biochemistry and Molecular Medicine, University of California, School of Medicine, Davis CA, and the ⁴Department of Veterans Affairs Northern California Health Care System, Mather, CA , USA
Background: Inflammation strongly predicts all-cause and cardiovascular mortality among dialysis patients. The negative acute-phase proteins, albumin and prealbumin are both inversely associated with mortality. Both albumin and prealbumin levels are decreased by inflammation. We carried out a pilot study to establish whether treatment with the tumor necrosis factor-α receptor antagonist etanercept would be safe and result in improved levels of albumin and prealbumin in inflamed hypoalbuminemic (albumin < 3.8 g/dl, CRP > 8.0 mg/l) prevalent hemodialysis patients. Methods: We excluded patients who had infectious risk (hepatitis C or B positive, HIV positive, purified protein derivative (PPD) positive or having a history of tuberculosis, having a tunneled dialysis catheter) to find patients having both hypoalbuminemia and inflammation. Of 433 less than 6% met the inclusion criteria. 10 patients were randomized to receive etanercept or placebo twice weekly for 44 weeks. Results: There were no adverse infectious events. There was no significant difference for any of the measurements between the two groups. However there was a significant difference in the time-dependent effects of etanercept on prealbumin: increasing 20% in the etanercept group while decreasing in the placebo group. Conclusions: Administration of a TNF-α receptor antagonist appears safe in this selected population, despite the large increase in infectious risk observed in the dialysis patient population. The effect on surrogate markers of inflammation is small. Correspondence to:
G.A. Kaysen MD, PhD
Division of Nephrology
Genome and Biomedical Sciences Facility
451 Health Sciences Drive
University of California
Davis, CA 95616, USA
Email: [email protected]

Abstract

Clinical Nephrology, Vol. 74 – No. 2/2010 (159-163)

A case of acute phosphate nephropathy in a patient with nephrotic syndrome and decreased serum fetuin-A

S.H. Han¹,²*, J.E. Lee¹*, S.H. Lee¹, J.J. Li³, S.W. Hong⁴, D.S. Han¹ and S.-W. Kang¹

¹Department of Internal Medicine, College of Medicine, Brain Korea ²¹ Project for Medical Science, Yonsei University, Seoul, ²Department of Internal Medicine, NHIC Ilsan Hospital, Goyangshi, Gyeonggi-do, Korea, ³Department of Internal Medicine, Nephrology and Dialysis Unit, the Affiliated Hospital, YanBian University Medical College, JiLin, China, and ⁴Department of Pathology, Yonsei University College of Medicine, Seoul, Korea

*These two authors contributed equally to this paper.
We report a case of APN after OSP use in a patient with nephrotic syndrome (NS). Renal biopsy revealed minimal change disease with multifocal calcium phosphate deposits within the tubules and in the interstitium. The serum level of fetuin-A, a systemic calcification inhibitor, was low during severely proteinuric state but normalized after remission of NS. To verify whether fetuin-A levels are low in NS patients, serum fetuin-A levels were determined in 10 patients with NS and 10 with asymptomatic microscopic hematuria (H). The mean serum fetuin-A levels were significantly lower in the NS group compared to the H group (p < 0.01). This finding suggests that a lower serum fetuin-A level may be associated with APN after OSP use in patients with NS, thus careful attention should be paid when colonoscopy using OSP is scheduled in this population.Correspondence to:
S.-W. Kang, MD, PhD
Department of Internal Medicine
Yonsei University College of Medicine
134 Shinchon-Dong
Seodaemoon-Gu, Seoul, 120-752, Korea
Email: [email protected]

Abstract

Clinical Nephrology, Vol. 75 – No. 2/2011 (135-140)

Erectile dysfunction in male hemodialysis patients in China – one center experience

J. Bao¹, Q. Yu¹, H. Yu², J. Hao¹, J. Liu¹, J. Yao¹ and W. Yuan¹

¹Department of Nephrology, Shanghai First People’s Hospital Affiliated to Jiaotong University, Shanghai, and ²The Affiliated Cardiovascular Hospital of Medical College, Qingdao University, Qingdao, Shandong Province, China
Objective: To evaluate the prevalence and the risk factors of erectile dysfunction in a Chinese cohort of hemodialysis (HD) patients. Methods: 63 male hemodialysis patients were assigned to HD group and 47 health volunteers were recruited as controls. The International Index of Erectile Function (IIEF-5) was used to assess erectile dysfunction (ED). All data were obtained by patient interviews and medical chart review. We measured the blood sex hormone of all the patients and volunteers. We divided those under 50 years HD patients into two groups according to erectile function (EF) score, Group A: EF score >= 12, no ED or mild ED; Group B: EF score < 12, moderate or severe ED. Results: The incidence of ED was significantly higher and the erectile function score was significantly lower in the HD group than that in the control group. The level of Follicle Stimulating Hormone, Luteinizing Hormone, Prolactin, Estradiol, Progesterone were significantly higher and the level of testosterone was significantly lower in the HD group than that in the control group. Patients in Group A were younger and duration of dialysis were shorter than patients in Group B. The level of High Density Lipoprotein was higher and FSH was lower in Group A than that in Group B. A significant negative correlation was found between the EF score and the age, duration of dialysis, the level of FSH and PRL in the HD group. There was a positive correlation trend between EF score and T level, but this did not reach statistical significance (p > 0.05). More patients had hypertension in the HD group. Conclusion: The age, duration of dialysis, hypertension, lipid disorder, the abnormality of hypothalamic-pituitary-gonadal axis were risk factors for ED in HD patients.Correspondence to:
Dr. Q. Yu
Shanghai First People’s Hospital Affiliated to Jiaotong University
100 Haining Road, Shanghai 200080, China
Email: [email protected]

Abstract

International Journal of Clinical Pharmacology and Therapeutics, Vol. 49 – No. 3/2011 (237-246)

Pharmacokinetics and bioequivalence of single dose and multiple doses of immediate- and extended-release formulations of dexibuprofen in healthy Chinese subjects

M.J. Xu¹, C. Zou¹, J.H Chu¹, T. Wu¹, S.J. Liu¹, J. Zhang¹, M. Chen¹, F. Liu¹, N.N. Xiong¹, W.Z. Ju¹ and H.S Tan²

¹Department of Clinical Pharmacology, Affiliated Hospital of Nanjing University of Traditional Chinese Medicine, and ²Department of Clinical Pharmacology, General Hospital of Nanjing Armed Forces, Nanjing, China
Objective: To compare the pharmacokinetic (PK) profiles and bioequivalence of the extended-release (ER) and immediate-release (IR) formulations of dexibuprofen (DI) in healthy Chinese volunteers after single dose and multiple doses. Materials: Zefen^® (IR capsule, containing 150 mg DI, Suzhou No.4 Pharmaceutical Factory, Jiangsu, China) and ER capsule (containing 225 mg DI, Tianjin Zhongtian Pharmaceutical Co. Ltd., Tianjin, China). Methods: This was an open, randomized, two-period crossover study. Eligible subjects were healthy male Chinese volunteers. 22 subjects were randomly assigned to receive a single 450 mg dose of the test or reference formulation on the first day. During the next 6 days, the test group received a multiple-dose of ER DI capsule (450 mg, b.i.d.) and the reference group took a multiple-dose of IR DI capsule (300 mg, t.i.d.), respectively. Multiple blood samples were collected, and plasma concentrations of DI were analyzed using high performance liquid chromatography (HPLC) system. After a 9-day washout period, the subjects were administered the alternate formulation. Bioequivalence was concluded if the 90% confidence interval (CI) for the ratio between test and reference was within accepted limits. Adverse events (AEs) were monitored and documented throughout the confinement in the clinic and washout phases of each study period. Results: 21 subjects completed the single dose administration and 20 subjects were evaluable for the multiple doses PK parameters. Single-dose Mean AUC_0-t and AUC_0-inf for ER formulation were 116.14 ± 21.54 mg·h/l and 117.60 ± 22.27 mg·h/l, and for IR formulation, were 107.25 ± 23.48 mg·h/l and 108.18 ± 23.93 mg·h/l, with the 90% CI within the limits accepted for bioequivalence. Mean C_max for ER and IR formulations were 22.30 ± 5.17 mg/l and 30.26 ± 13.54 mg/l, respectively. And median tmax for ER and IR formulations were 4.5 h and 2.0 h. The retard quotient (delta R) for ER product was 1.9 ± 0.93, which indicated an intermediate extended release effect. Multiple-dose Mean AUC_0-24 for ER formulation was 217.93 ± 41.07 mg·h/l and for IR formulation was 199.33 ± 37.32 mg·h/l. Other PK parameters of ER and IR formulations were as follows: median t_max were 4.8 h and 2.0 h, C_ss-max were 20.21 ± 2.69 mg/l and 19.71 ± 3.46 mg/l, C_ss-min were 2.47 ± 0.99 mg/l and 2.48 ± 0.99 mg/l, C_av were 9.08 ± 1.71 mg/l and 8.31 ± 1.56 mg/l, respectively. Conclusions: This study found that in these subjects, the absorption rates of the two DI formulations were not bioequivalent, but at steady state, the daily exposure provided by less frequent DI ER dosing was not significantly different from the same daily dose with DI IR capsules, administered more frequently.Correspondence to:
W.Z. Ju, PhD
Department of Clinical Pharmacology
Affiliated Hospital of Nanjing
University of Traditional Chinese Medicine
Nanjing, China
Email: [email protected]

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