Agreement between functional residual capacity estimated via automated gas dilution versus via computed tomography in a pleural effusion model. The measurement of functional residual capacity (FRC) in ventilated patients could help track the extent of acute lung disease, monitor recruitment of unstable lung units, or guide the use of PEEP. Quantitative analysis of computed tomography (CT) images of the lungs is currently the accepted standard for FRC measurement (FRC-CT), but is impractical for routine use. Gas dilution and gas tracer technologies, while attractive for research applications, require specialized equipment and skills missing from the clinical setting. We simultaneously evaluated FRC-CT and FRC determined by a ventilator-incorporated wash-in/wash-out (FRC-WI/WO) method in an animal model of unilateral pleural effusion that varied the fluid volume instilled and the applied PEEP. A swine model (n = 6) of unilateral pleural effusion was created by injecting boluses of radio-opaque fluid (iopromide) (13 mL/kg and then 26 mL/kg) into the right thoracic cavity. FRC-CT and FRC-WI/WO were simultaneously obtained, at 2 PEEP levels, at baseline and at both pleural-effusion volumes. A correlation coefficient (r²) of 0.89 between FRC-CT and FRC-WI/WO revealed concordance between the techniques, with directional agreement and acceptable bias and precision under all tested conditions. We found excellent concordance between FRC-WI/WO and FRC-CT in an animal model of unilateral pleural effusion that stressed the capability of this technology. The technical advantage of the wash-in/wash-out technique is its incorporation into ventilator operation without requiring adjustments to ventilation.


Radiation dose to patients and clinicians during fluoroscopically-guided biopsy of peripheral pulmonary lesions. Fluoroscopic guidance may be utilized in some bronchoscopic procedures, including ultrasound-guided bronchoscopy for investigation of peripheral pulmonary lesions. Some authors have suggested this procedure may be performed without fluoroscopy, to minimize risks due to radiation exposure. However, the radiation dose has never been quantified, so the risk remains unknown. To determine the patient and clinician radiation exposure from fluoroscopy during bronchoscopy. We recorded exposure parameters during 45 consecutive ultrasound bronchoscopies with fluoroscopic guidance with a mobile C-arm fluoroscopy system. We calculated the patient effective radiation dose with Monte Carlo computer simulations. Passive personal film dosimeters were placed on 4 sites on both the proceduralist and the primary nursing assistant. The mean fluoroscopy screening time was 96 ± 55 s. Patients received a median effective radiation dose of 0.49 ± 0.37 milli-Sieverts (mSv) (range 0.16-1.3 mSv). Only the film dosimeters worn outside the clinicians' protective aprons recorded measurable radiation doses. Based on typical attenuation properties of the protective garments across the diagnostic x-ray energy range, we estimate that the effective radiation dose per procedure to the proceduralist was 0.4 micro-Sieverts (μSv) and to the assistant was 0.2 μSv. Patients are exposed to relatively small amounts of radiation from fluoroscopy during bronchoscopy. Clinically indicated fluoroscopic guidance during bronchoscopy should not be precluded on the basis of radiation safety concerns. Adequate shielding of clinicians results in negligible radiation doses during ultrasound bronchoscopy.


Goal-directed therapy for severely hypoxic patients with acute respiratory distress syndrome: permissive hypoxemia. Permissive hypoxemia is a lung-protective strategy that aims to provide a patient with severe acute respiratory distress syndrome (ARDS) a level of oxygen delivery that is adequate to avoid tissue hypoxia while minimizing the detrimental effects of the often toxic ventilatory support required to maintain normal arterial oxygenation. However, in many patients with severe ARDS it can be difficult to achieve a balance between maintaining adequate tissue oxygenation and avoiding ventilator-induced lung injury (VILI). A potential strategy for the management of such patients involves goal-oriented manipulation of cardiac output and, if necessary, hemoglobin concentration, to compensate for hypoxemia and maintain a normal (but not supranormal) value of oxygen delivery. Although it has not yet been studied, this approach is theorized to improve clinical outcomes of critically ill patients with severe ARDS. We stress that the goal of this article is not to convince the reader that this approach is necessarily correct, as data are clearly lacking, but rather to provide a basis for continued thought, discussion, and potential research.


Chemotherapy-associated recurrent pneumothoraces in lymphangioleiomyomatosis. Lymphangioleiomyomatosis is a rare cause of pneumothorax in women. We present the case of a 48-year-old woman with lymphangioleiomyomatosis, who had never had a pneumothorax prior to commencing chemotherapy for breast cancer. During chemotherapy she developed 3 pneumothoraces and 2 episodes of pneumomediastinum. We suggest that the pneumothoraces were caused by the chemotherapy. To our knowledge, this is the first reported case of chemotherapy triggering pneumothoraces in a woman with lymphangioleiomyomatosis.


Intercostal artery laceration following thoracentesis. Intercostal artery laceration is an unusual complication following thoracentesis, and has been reported only in elderly patients. We report a case of a 78-year-old man who developed a massive hemothorax following thoracentesis. Post-thoracentesis radiograph revealed a substantial increase in pleural fluid, and emergency chest tube insertion identified the hemothorax. He underwent right thoracotomy for repair of the intercostal artery laceration.


Tai chi exercise for patients with chronic obstructive pulmonary disease: a pilot study. To determine the feasibility of a randomized controlled trial of the effect of a tai chi program on quality of life and exercise capacity in patients with COPD. We randomized 10 patients with moderate to severe COPD to 12 weeks of tai chi plus usual care (n = 5) or usual care alone (n = 5). The tai chi training consisted of a 1-hour class, twice weekly, that emphasized gentle movement, relaxation, meditation, and breathing techniques. Exploratory outcomes included disease-specific symptoms and quality-of-life, exercise capacity, pulmonary function tests, mood, and self-efficacy. We also conducted qualitative interviews to capture patient narratives regarding their experience with tai chi. The patients were willing to be randomized. Among 4 of the 5 patients in the intervention group, adherence to the study protocol was excellent. The cohort's baseline mean ± SD age, percent-of-predicted FEV₁, and ratio of FEV₁ to forced vital capacity were 66 ± 6 y, 50 ± 12%, and 0.63 ± 0.14, respectively. At 12 weeks there was significant improvement in Chronic Respiratory Questionnaire score among the tai chi participants (1.4 ± 1.1), compared to the usual-care group (-0.1 ± 0.4) (P = .03). There were nonsignificant trends toward improvement in 6-min walk distance (55 ± 47 vs -13 ± 64 m, P = .09), Center for Epidemiologic Studies Depression Scale (-9.0 ± 9.1 vs -2.8 ± 4.3, P = .20), and University of California, San Diego Shortness of Breath score (-7.8 ± 3.5 vs -1.2 ± 11, P = .40). There were no significant changes in either group's peak oxygen uptake. A randomized controlled trial of tai chi is feasible in patients with moderate to severe COPD. Tai chi exercise as an adjunct to standard care warrants further investigation.


Cryptococcosis in the immunocompetent patient.


Obesity hypoventilation syndrome: bicarbonate concentration and acetazolamide.


Flutter-type mucus-clearance devices and pulmonary function in the elderly.


Randomised trials on vitamin C.

Randomised trials on vitamin C.


Amelioration of hyperglycaemia and its associated complications by finger millet ( Eleusine coracana L.) seed coat matter in streptozotocin-induced diabetic rats. Finger millet (Eleusine coracana) is extensively cultivated and consumed in India and Africa. The millet seed coat is a rich source of dietary fibre and phenolic compounds. The effect of feeding a diet containing 20% finger millet seed coat matter (SCM) was examined in streptozotocin-induced diabetic rats. Diabetic rats maintained on the millet SCM diet (diabetic experimental (DE) group) for 6 weeks exhibited a lesser degree of fasting hyperglycaemia and partial reversal of abnormalities in serum albumin, urea and creatinine compared with the diabetic control (DC) group. The DE group of rats excreted comparatively lesser amounts of glucose, protein, urea and creatinine and was accompanied by improved body weights compared with their corresponding controls. Hypercholesterolaemia and hypertriacylglycerolaemia associated with diabetes were also notably reversed in the DE group. Slit lamp examination of the eye lens revealed an immature subcapsular cataract with mild lenticular opacity in the DE group of rats compared to the mature cataract with significant lenticular opacity and corneal vascularisation in the DC group. Lower activity of lens aldose reductase, serum advanced glycation end products and blood glycosylated Hb levels were observed in the DE group. The millet SCM feeding showed pronounced ameliorating effects on kidney pathology as reflected by near normal glomerular and tubular structures and lower glomerular filtration rate compared with the shrunken glomerulus, tubular vacuolations in the DC group. Thus, the present animal study evidenced the hypoglycaemic, hypocholesterolaemic, nephroprotective and anti-cataractogenic properties of finger millet SCM, suggesting its utility as a functional ingredient in diets for diabetics.


Follicular interactions affect the in vitro development of isolated goat preantral follicles. The aim of this study was to evaluate the influence of the number of follicles per drop (one or three) and antral follicles on in vitro development of isolated goat preantral follicles. Preantral follicles were isolated through microdissection and distributed individually (control) or in groups of three follicles (treatment) in microdroplets of α-MEM with or without 1000 ng/ml follicle stimulating hormone (FSH) for Experiments 1 and 2, respectively. Experiment 3 was divided into four treatments according to the presence of one or three preantral follicles, associated or not with antral follicles. After culture, oocytes were retrieved from morphologically normal follicles and submitted to in vitro maturation (IVM) and live/dead fluorescent labelling. Results of Experiment 1 (basic medium without FSH) showed that culture of preantral follicles in groups enhances viability, growth and antrum formation after 12 days. However, in the presence of FSH (Experiment 2), only the recovery rate of fully grown oocytes for IVM was significantly affected by grouping of follicles. In Experiment 3, in general, co-culture of preantral follicles with an early antral follicle had a detrimental effect on viability, antrum formation and production of oocytes for IVM. In conclusion, the performance of in vitro culture of goat preantral follicles is affected by the number of follicles per drop, the presence of an antral follicle and FSH.


Early presentation of endomyocardial fibrosis in a 22-month-old child: a case report. We present an unusual, biopsy-proven case of endomyocardial fibrosis in a 22-month-old male child, which progressed rapidly resulting in death. The patient was born to a father originating from Mozambique, where the disease is endemic but who had not himself travelled there, suggesting a genetic link. Other remarkable features were the presence of a right ventricular diverticulum, and a positive Mycoplasma pneumoniae immunoglobulin M enzyme-linked immunosorbent assay test.


Getting out what we put in: productivity of the English National Health Service. Many countries are incorporating direct measures of non-market outputs in the national accounts. For any particular output to be included there has to be data about it for two adjacent periods. This is problematic because the classification of non-market outputs is often subject to wholesale revision. We outline the challenges associated with classification changes and propose a solution. To illustrate we construct output and input indices and estimate productivity growth of the English National Health Service (NHS) for the period 2003-2004 to 2007-2008. Our index of output growth incorporates all care provided to NHS patients and captures improvements in survival rates, waiting times and disease management. We find that more patients are being treated and the quality of the care they receive has been improving. We implement our approach to dealing with changes as to how health services are defined and show what effect this has on estimates of output growth. Our index of input growth captures all labour, intermediate and capital inputs into health service production and we improve on how capital has been measured in the past. Inputs have increased over time but there has also been a slowdown since 2005-2006, primarily the result of a levelling off in staff recruitment and less reliance on the use of agency staff. Productivity is assessed by comparing output growth with growth in inputs, the net effect being constant productivity growth between 2003-2004 and 2007-2008.


PEGylated guanidinylated polyallylamine as gene-delivery carrier. A novel cationic co-polymer was developed by grafting poly(ethylene glycol) (PEG) on guanidinylated polyallylamine (PAA) for gene delivery. Characterization of PEG-g-guanidinylated PAA/DNA complexes demonstrated that particle size increased and surface charge decreased with increasing the amount of PEG. The results of cytotoxicity assay proved that grafted PEG could effectively decrease the cytotoxicity of the complexes. In transfection efficiency assay, HeLa cells treated with PEG(2)-g-guanidinylated PAA (formed with 17.5 μmol guanidinylated PAA and 2 μmol PEG)/DNA (0.2 μg EGFP plasmid) complexes showed a very high level of EGFP expression. In conclusion, combination of guanidinylation and PEGylation could effectively decrease the cytotoxicity and significantly increase the transfection efficiency of PAA.


Using CT imaging to delineate the prostatic apex for radiation treatment planning. In computed tomography (CT)-based radiotherapy planning for prostate cancer, it is difficult to precisely delineate the prostatic apex because of its relationship with the urogenital diaphragm and bulbospongiosus musculature. In this retrospective study, we analyzed the magnetic resonance imaging (MRI) and CT scans of the patients with prostate cancer to investigate the relationship between the prostatic apex and the anatomic structure visible on CT, and to provide evidence for localizing the prostatic apex in radiotherapy planning. MRI and CT scans of 108 patients with prostate cancer were analyzed to measure the distances between the prostatic apex and the bottom of ischial tuberosities, the bottom of obturator foramen, the bottom of pubic symphysis, and the bulb of the penis. The volume of the prostate was measured to analyze its relationship with the localization of the prostatic apex. The prostatic apex was located (13.1±3.3) mm above the bulb of the penis, (11.0±5.4) mm above the bottom of the obturator foramen, (31.3±5.5) mm above the ischial tuberosities, and (7.1±4.7) mm above the bottom of the symphysis pubis. There was no correlation between the size of the prostate and the localization of the prostatic apex. The variance of the distance between the prostatic apex and the bulb of the penis is smaller than that of the distance between the apex and bony anatomy. Delineating the target to 6 mm above the bulb of the penis can cover the prostatic apex in 95% of the patients with prostate cancer, delineating to the bottom of obturator foramen can cover the prostatic apex in 100% of the patients.


Structure and biocompatibility of an injectable bone regeneration composite. With the development of minimally invasive techniques, injectable materials have become one of the major hotspots in the biomaterial field. We have developed an injectable bone regeneration composite (IBRC) using calcium alginate hydrogel as matrix to carry nano-hydroxyapatite/collagen particles. In this work, we evaluated the homogeneity of IBRC by dry/wet weight ratio test. The results showed that the structural homogeneity was determined by controlling the molar ratios of trisodium phosphate to calcium sulfate rather than alginate concentration in the studied ranges. Pore sizes of wet IBRC samples were characterized by thermoporometry. The pore properties of dried IBRC were tested by mercury porosimetry. Average pore size and porosity of dried IBRC declined with increasing alginate concentration. In contrast, surprisingly, pore size of wet homogeneous IBRC increased with increasing alginate concentration. Meanwhile, the swelling ratio did not increase with varying alginate concentration, but the swelling degree increased with increasing alginate concentration. In vitro cell culture showed that IBRC had no obvious cytotoxic effect on the rat bone mesenchymal stem cells. The morphology and viability of cells were also related to MR value. IBRC had good histocompatibility with a mild short-term inflammatory response in rat dorsum muscle. In addition, the excellent ability of IBRC to promote bone healing was confirmed by 5-mm-diameter cranial defects using histological analysis and bone mineral density measurement.


Adjuvant interferon therapy for malignant melanoma: the debate. Based on the results of the Kirkwood high-dose interferon alpha-2b (HDI) adjuvant therapy trial of the Eastern Cooperative Oncology Group 1684, the US Food and Drug Administration (FDA) approved HDI as the postoperative adjuvant therapy for high-risk melanoma. Unfortunately, controversies continue regarding the use of interferon (IFN) as adjuvant therapy for melanoma owing to the inconsistent results of subsequent trials. Numerous trials of adjuvant interferon therapy demonstrated a benefit in terms of relapse-free survival (RFS), but without confirmed significant effect on overall survival (OS). The optimal timing, dose, and type of interferon are not yet defined. Therefore, adjuvant interferon treatment is preferentially applied in the randomized clinical trials in specialized centers. Decisions about the appropriateness of adjuvant interferon alfa-2b treatment for patients should be made on an individual basis, after discussion with the patient, including an explanation of the potential benefits and side effects of interferon therapy. Moreover, we also need to use available regimens reasonably, seek feasible and predictable prognostic factors to serve patients with individualized therapy.


Prognosis of 980 patients with gastric cancer after surgical resection. Although surgery is the only possible means to cure gastric cancer, the prognosis is often discrepant. The American Joint Committee on Cancer / International Union against Cancer (AJCC/UICC) published the TNM classification of Malignant Tumors (seventh edition) for gastric cancer recently. This study aimed to use this new edition staging system to investigate the prognostic factors for gastric cancer. The clinicopathologic data of 980 patients with gastric cancer treated by surgical resection in our hospital between January 2000 and December 2006 were analyzed retrospectively. The overall survival rate was determined by using Kaplan-Meier method and log-rank test was used to determine significance. The prognosis was analyzed using univariate analysis and multivariate analysis with the Cox proportional hazards model. The 6th and 7th edition AJCC/UICC TNM staging systems were used to compare the survival outcomes for the cohort of patients. The overall 1-, 3-, 5-year survival rates for the whole group were 82.5%, 58.7%, and 52.6%. The 5-year survival rates for patients with pTNM stage I, II, III, and IV disease classified by the 7th edition staging system were 93.2%, 72.4%, 39.1%, and 5.2%, respectively. In both univariate analysis and Cox multivariate analysis, age, tumor site, tumor size, histological type, resection type, radical resection, lymphatic/venous invasion, depth of invasion, nodal status, metastasis, retrieved lymph nodes, metastatic lymph node ratio, and adjuvant chemotherapy were prognostic factors with these patients. Compared with the 6th edition system, the new edition of TNM staging system for gastric cancer can accurately predict the survival after operation.


Relationship between traditional Chinese medicine syndrome differentiation and imaging characterization to the radiosensitivity of nasopharyngeal carcinoma. Traditional Chinese medicine (TCM) is a well established and time-honored practice in China, employing syndrome differentiation as a basis for the treatment of disease. According to different TCM syndrome typing findings, combining modern medical methods with TCM approaches can improve the quality of life and comprehensive effect on patients with nasopharyngeal carcinoma (NPC). This study investigated the relationship between TCM syndrome typing and imaging characterization to radiosensitivity as to provide objective evidence for the integration of Chinese and modern medical approaches in the treatment of NPC. Prior to treatment, TCM syndrome typing, computed tomography (CT) and magnetic resonance imaging (MRI) were performed on 147 patients pathologically classified with NPC. The status of tumor remission was radiologically evaluated at accumulated doses of 20 Gy, 40 Gy and 60 Gy, and at 3 months after completion of radiotherapy. Statistical results were analyzed by the Friedman and K-W test procedures. Prior to treatment, TCM syndrome typing of NPC included Lung Heat, Blood Stasis, Phlegm Congealment and Blood Stasis-Phlegm Congealment. Lung Heat typing accounted for the highest proportion at 34.7% (51/147), followed by Phlegm Congealment at 32.7% (48/147), Blood Stasis at 17.0% (25/147) and Blood Stasis-Phlegm Congealment at 15.7% (23/147). Radiological imaging demonstrated a higher incidence of cervical lymph node metastases in Phlegm Congealment and Blood Stasis-Phlegm Congealment types (P<0.05), while Blood Stasis and Blood Stasis-Phlegm Congealment types were more prone to skull base invasion (P<0.05). Residual tumor size was larger in Blood Stasis and Blood Stasis-Phlegm Congealment types than in Lung Heat and Phlegm Congealment types after 3 months of treatment (P<0.05). Different radiological manifestations were observed in TCM syndrome typed NPC patients, with lesser radiosensitivity demonstrated in the Blood Stasis and the Blood Stasis-Phlegm Congealment types relative to the Lung Heat and Phlegm Congealment types.


Expression of BC047440 protein in hepatocellular carcinoma and its relationship to prognosis. BC047440 is a new gene related to cancer growth and proliferation. Due to the lack of specific antibodies, how BC047440 protein influences the liver cancer growth is unclear. This study aimed to determine the relationship between BC047440 protein expression and clinicopathologic parameters of hepatocellular carcinoma (HCC), and to evaluate the prognostic value of BC047440 for HCC patients. We prepared the polyclonal antibodies of BC047440, and used Western blot and immunohistochemical staining to detect BC047440 expression in 68 specimens of HCC. The correlations of BC047440 expression to clinicopathologic features and prognosis of HCC patients were analyzed. The polyclonal antibodies could effectively recognize endogenous BC047440 in HCC tissues. The positive rate of BC047440 protein was significantly higher in HCCs than in adjacent tissues (44.1% vs. 23.5%, P<0.05); the rate was significantly higher in patients with larger tumor (P<0.05) and portal vein invasion (P<0.01). The HCC patients with high BC047440 expression showed a significantly poorer prognosis than those with low BC047440 expression (P<0.05). BC047440 can promote the growth and invasion of HCC.


Risk factors for acute kidney injury in patients undergoing allogeneic hematopoietic stem cell transplantation. Allogeneic hematopoietic cell transplantation (allo-HSCT) is a potent procedure for the treatment of hematologic diseases, yet it is associated with high risks of treatment-related complications. Except for transplant-related organ toxicities, renal insufficiencies which emerge earlier significantly limit patients' long survival. To analyze risk factors for acute kidney injury (AKI), we conducted a retrospective cohort study of 96 patients undergoing HSCT. During the first 100 days after allo-HSCT, all patients were evaluated for renal function by measuring serum creatinine clearance and glomerular filtration rate (GFR) with a classification below: Grade 0 (<25%, decline in creatinine clearance), Grade 1 (≥25% decline in creatinine clearance but <2-fold increase in serum creatinine), Grade 2 (≥2-fold rise in serum creatinine but no need for dialysis), and Grade 3 (≥2-fold rise in serum creatinine and need for dialysis). Cox regression model was used to calculate the hazard ratios (HRs) of demographic data, clinical variables, and risk factors for AKI. Twenty-eight (29.2%) patients occurred Grades 1-3 renal dysfunction (Grade 1, 14 patients; Grade 2, 12 patients; Grade 3, 2 patients), and ratios of early kidney injury increased in high-risk malignancy group (HR = 2.945, 95% confidence interval (CI)=1.293-6.421), patients treated with myeloablative conditioning regimen (HR=2.463, 95% CI=1.757-4.320), and patients with acute GVHD (HR=3.553, 95% CI=1.809-6.978), sepsis (HR=3.215, 95% CI=1.189-6.333 ), or hepatic veno-occlusive disease (VOD) (HR=3.487, 95% CI=1.392-6.524). Whereas, HLA histocompatibility showed no striking increased risk for acute renal injury (HR=1.684, 95% CI=0.648-4.378). The survival rate was lower in patients with severe nephrotoxicity (21.4%) than in patients without nephrotoxicity (70.6%) (P=0.001). Nephrotoxicity is the primary risk factor for AKI, severely impacting on survival. Sorts of risk factors mentioned will be useful for evaluation for kidney function of patients undergoing allo-HSCT.


Efficacy of concurrent chemoradiotherapy plus adjuvant chemotherapy on advanced cervical cancer. Concurrent chemoradiotherapy for cervical carcinoma develops rapidly and has become a common and standard therapy in recent years. Both the local control rate and survival rate of patients were increased and the risk of death fell by 30%-50%. This study aimed to explore the efficacy of concurrent chemoradiotherapy plus adjuvant chemotherapy on and the treatment compliance of the patients with advanced cervical squamous cell carcinoma. A total of 156 patients with stage IIa-IIIb cervical squamous cell carcinoma were randomly divided into the concurrent chemoradiotherapy group (experimental group) and radiotherapy group (control group). Intracavity and external beam radiation therapy were administered. At point A, 40-48 Gy were given by 10-12 fractions; at point B, 46-50 Gy were given by 23-25 fractions. In the same time, experimental group was treated by cisplatin (DDP, 40 mg) on day 1, repeated every week. Ten days after radiation therapy, TP regimen was administered as adjuvant chemotherapy. For the experimental and control groups, the objective response rates were 88.61% and 75.32%, 1-year survival rates were 88.57% and 70.77%, 1-year local control rates were 81.43% and 64.62%, 3-year survival rates were 82.14% and 57.69%, and 3-year local control rates were 75.00% and 46.15%, with significant differences (P<0.05). Quality of life of all patients were significantly improved after treatment (P<0.05). Concurrent chemoradiotherapy plus adjuvant chemotherapy for advanced cervical cancer can improve short-term and long-term survival and local control rates of patients, improve the quality of life, and the toxicity can be tolerated.


The recruitment of exogenous endothelial progenitor cells in lung tumor model of nude mice. Endothelial progenitor cells (EPCs) play an important role in hypoxia-triggered tumor vasculogenesis. However, the homing of exogenous EPCs in tumors is still unclear. In this study, we investigated the recruitment of exogenous EPCs in human lung adenocarcinoma model of nude mice. EPCs labeled with green fluorescence protein (GFP) were transplanted into nude mice bearing human lung adenocarcinoma. The growth of tumor was observed. After the mice were killed, GFP-EPCs in different tissues were examined by fluorescence. The tumor tissues were stained for CD133, hypoxia-inducible factor-1alpha (HIF-1α), stromal cell-derived factor-1α (SDF-1α), and vascular endothelial growth factor receptor (KDR). Real-time polymerase chain reaction of CD133, HIF-1α, SDF-1α, and VEGF-1 were also performed. The growth of tumor in EPC group was significantly faster than that in saline solution group (P <0.05). Under fluorescence microscope, GFP-EPCs were strongly expressed in both tumor and bone marrow. EPCs were recruited to the tumor periphery to participate in tumor vasculogenesis. The expression of CD133, HIF-1α, and SDF-1 mRNA in tumor and bone marrow were significantly higher than that in the liver, spleen, and skin (P<0.05). Exogenous EPCs can be recruited to tumor and accelerate tumor growth. Except tumor, bone marrow can also recruit EPCs.


Primary malignant bone neoplasm: a case report of dedifferentiated chondrosarcoma in the rib and review of the literature. Dedifferentiated chondrosarcoma (DDCS) is a rare but highly malignant primary bone neoplasm, which is resistant to radiotherapy and chemotherapy. There remains uncertainly as to the best treatment of this disease and how to improve its prognosis. In this paper we reported a case of DDCS and reviewed the related literatures in order to provide references to throw a light on the histogenesis, diagnosis and therapy of this disease.


Anti-cancer effects of Phyllanthus urinaria and relevant mechanisms. Phyllanthus urinaria (P. urinaria), a widely used herbal medicine, has been reported to possess various biological activities. This report aimed to characterize the whole P. urinaria plant, present the anticancer effects of P. urinaria both in vivo and in vitro, and explore relevant mechanisms. The water extract of P. urinaria not only significantly reduces the cell viability of various cancer cell lines from different origins but also suppresses tumor development in C57BL/6J mice after implantation of Lewis lung carcinoma (LCC) cells. The anticancer activity of P. urinaria extract is mainly due to induced apoptosis of cancer cells as demonstrated by DNA fragmentation and increased caspase-3 activity through both intrinsic and extrinsic pathways. The decrease in viability with P. urinaria treatment might be partially associated with down-regulation of telomerase activation and induction of the apoptotic process. In addition, P. urinaria also exhibits anti-angiogenic activity that is mediated, at least in part, by suppression of matrix metalloproteinase 2 (MMP-2) secretion and inhibition of MMP-2 activity through zinc chelation.


Current status of surgical treatment for hemorrhoids--systematic review and meta-analysis. Hemorrhoids are one of the most common anorectal disorders. Conventional hemorrhoidectomy is the most commonly practiced surgical technique. Stapled hemorrhoidectomy (procedure for prolapse and hemorrhoids [PPH]) and Ligasure hemorrhoidectomy are newly developed methods for the surgical management of hemorrhoids. The objective of this study was to compare the effectiveness and safety of these two novel techniques with that of conventional hemorrhoidectomy. From the MEDLINE data-base, we obtained papers published between January 2000 and September 2009 and retrospectively studied randomized, controlled clinical trials that compared PPH versus conventional hemorrhoidectomy or Ligasure hemorrhoidectomy versus conventional hemorrhoidectomy. Both PPH and Ligasure hemorrhoidectomy were superior to conventional hemorrhoidectomy with regard to operation time, early postoperative pain, urinary retention, and time to return to normal activity. However, skin tags and recurrent prolapse occurred at higher rates in the PPH group. Although both new techniques have short-term benefits, especially in reducing extreme postoperative pain, more powerful clinical studies with long-term follow up and larger sample sizes should be conducted for further evaluation of outcomes.


Down-regulation of insulin-like growth factor I (IGF-I) in the mouse diaphragm during sepsis. Diaphragmatic muscle impairment is an important cause of respiratory failure during sepsis. Insulin-like growth factor I (IGF-I) is an anabolic growth factor which prevents muscle degradation and wasting during sepsis, but its role in the diaphragmatic muscle during sepsis is unknown. The aim of this study was to investigate the expression of IGF-I in the diaphragmatic muscle in a murine model of sepsis induced by lipopolysaccharide (LPS). Male B57 mice were peritoneally injected with LPS, and were killed and studied at different time-points, 24 h, 48 h, 72 h, and 96 h after injection. Diaphragm sarcolemmal damage was visualized by orange tracer dye infusion, and the expression of IGF-I, interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in diaphragm tissue extracts were measured using ELISA. LPS induced sarcolemmal damage in diaphragm myofibers from 24 h to 96 h, which was accompanied by a significant increase in IL-1β expression in the tissues while IGF-I levels were down-regulated. No change in TNF-α was observed. Body weights of animals were also reduced, especially at 96 h. The expression of IGF-I in diaphragm tissues was down-regulated during sepsis- induced diaphragm myofiber damage, suggesting that IGF-I may be an important factor in the regulation of diaphragm myofiber repair. Further studies are needed to examine the mechanisms involved.


The use of simvastatin with aromasin in an ovariectomized rat model: effects on the skeletal system. Many studies have reported the positive effect on bones of statins that inhibit the action of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase and suppress hepatic cholesterol biosynthesis. Recent data suggest that statins used in the treatment of hypercholesterolemia decrease fracture risk and increase bone mineral density (BMD). Aromasin (an aromatase inhibitor) is an effective and well-tolerated drug used in endocrine therapy for the treatment of hormone-sensitive early breast cancer in postmenopausal patients. It has a catabolic effect on the skeletal system and can therefore significantly increase the incidence of fractures. Our study aims to determine the effects of Aromasin and simvastatin plus Aromasin on the BMD in an ovariectomized rat model. In total, 27 female Sprague Dawley rats were subjected to a bilateral oophorectomy. One month after the oophorectomy, the rats were divided into the following 3 groups: (1) The control group, in which water was administered; (2) the Aromasin group in which Aromasin was administered orally; and (3) the Aromasin plus simvastatin group in which a combination of Aromasin and simvastatin was administered orally. The BMD of the lumbar spine (L1-L5) and left femoral bone was measured using dual-energy X-ray absorptiometry (DXA) 1 month after the ovariectomy and 3 months after treatment began. Blood was drawn at the time of oophorectomy and 3 months after treatment began to check the levels of calcium, phosphorus, and alkaline phosphatase (alk-ptase). In the Aromasin plus simvastatin group, the BMD of both the lumbar spine (p=0.003) and the left femoral bone (p=0.001) increased significantly after 3 months of treatment. In comparison with the Aromasin group, the Aromasin plus simvastatin group showed a significant increase in the BMD of both the lumbar spine and the left femoral bone (p=0.04 and p=0.005 respectively). In the Aromasin group, the BMD of the left femoral bone (p=0.01) and that of the lumbar spine both decreased significantly (p=0.001). The calcium, phosphorus, and alk-ptase levels were not significantly different among the 3 groups. In the Aromasin group, catabolic effects on the skeletal system were observed. In the Aromasin plus simvastatin group, the BMD significantly increased. Thus statins may have therapeutic application in the treatment of osteoporosis using Aromasin since they can counterbalance the adverse effects of this drug.


Comparison of airway hyperreactivity in chronic obstructive pulmonary disease and asthma. Airway hyperreactivity (AHR) has been described in patients with chronic obstructive pulmonary disease (COPD). However, the nature and characteristics of AHR in this disease have not been fully investigated. AHR was examined in a sample of 33 patients with COPD and 25 with asthma and compared during continuous inhalation of stepwise increased concentrations of methacholine. Respiratory resistance (Rrs) was measured by the forced oscillation technique and the dose-response curves were recorded. The mean values for both forced vital capacity (FVC) and forced expiratory volume in 1s (FEV1) were well-preserved in subjects with asthma. In contrast, there was an obstructive ventilatory defect in patients with COPD, as evidenced by the FEV1/FVC ratio, which fell below 70%. Upon methacholine challenge, only 54.5% (18/33) of the patients with COPD had AHR, compared with 100% (25/25) of those with asthma. Analysis of the dose-response curves revealed that the patients with COPD had a significantly higher baseline Rrs, and thus lower baseline respiratory conductance (Grs), than those with asthma. The cumulative dose of methacholine capable of provoking a positive reaction was significantly higher in patients with COPD. The slope of the Grs was also less steep in responders with COPD. There was good correlation between the severity of AHR and the initial level of airway narrowing in patients with COPD (r=0.623, p<0.01), but not in those with asthma. AHR is not uncommon in COPD, and it has different characteristics from that occurring in asthma.


A case of phlebosclerotic colitis with involvement of the entire colon. Phlebosclerotic colitis is a rare type of ischemic colitis caused by obstruction of the veins in the intestinal wall and adjacent mesentery, and is most commonly seen in the ascending colon. We report a 56-year-old woman presenting with intermittent abdominal pain and diarrhea for three years. She had a liver abscess and two episodes of pancreatitis during this time and experienced progressive body weight loss. Initial radiologic findings showed multiple tortuous threadlike calcifications in the region of the right side of the colon and transverse colon on plain abdominal radiographs and computed tomography images. A colonoscopy demonstrated brownish-black pigmentation on the right side of the colon with scattered hyperemic patches. The more distal along the colon, the more normal the color of the bowel appeared. Follow-up studies revealed calcifications not only alongside the colonic and mesenteric veins, but also extending into the superior and inferior mesenteric veins. These findings have not been reported previously. As noted in our patient, this disease entity may not be confined to the tributaries of the superior mesenteric vein. The entire colon may be involved in advanced disease.


Characteristics of Klebsiella pneumoniae bacteremia in community-acquired and nosocomial infections in diabetic patients. Although diabetes mellitus is known as a major risk factor for Klebsiella pneumoniae infection, the differences in clinical characteristics between community-acquired and nosocomial K. pneumoniae bacteremia in diabetic patients have been rarely reported. This retrospective analysis enrolled 193 adult diabetic patients with K. pneumoniae bacteremia hospitalized between January 2005 and December 2006. The chi-squared test, analysis of variance (ANOVA), Student's t test, Fisher exact test, and Cox regression model were used for statistical analysis. Of the enrolled patients, 147 had community-acquired infections and 46 had nosocomial infections. Compared with the community group, the nosocomial group had higher rates of in-hospital mortality (41.3% vs. 18.4%, p=0.001), malignancy (50.0% vs. 19.0%, p<0.001), and leukopenia (21.7% vs. 5.4%, p=0.001) but had lower levels of serum C-reactive protein (124.3 mg/L vs. 188.7 mg/L, p=0.018) and HbA1c (8.1% vs. 9.5%, p=0.025). The rate of infection with the extended-spectrum β-lactamase-producing strain (ESBL infection) in the nosocomial group was 11 times higher than that in the community group (45.7% vs. 4.1%, p<0.001). ESBL infection accounted for 53% of mortality in the nosocomial group. Pneumonia was more common in the nosocomial group, while local abscess was more common in the community group. The risk factors for mortality were pneumonia, leukopenia, cirrhosis, and a high serum creatinine ratio (creatinine level at admission/baseline). The nosocomial group had more ESBL infections which might account for the higher mortality. The HbA1c level during the course of infection did not affect the outcome. Pneumonia, leukopenia, cirrhosis, and a high serum creatinine ratio at admission were the risk factors for poor outcome.


Misdiagnosed acute appendicitis in children in the emergency department. To identify clinical features that distinguish children with appendicitis who visited the emergency department twice or more from those diagnosed on the first visit to the emergency department. A retrospective review of all children with appendicitis diagnosed in the emergency department between January and December 2004 was conducted. Records were reviewed for all patients on their initial presentation to the emergency department. Clinical features were compared between those children who were misdiagnosed and those who were diagnosed correctly. One hundred seventy-three cases were included (mean age, 10.4 years). Twenty-six (15%) were seen twice or more in the emergency department before appendicitis was diagnosed. Misdiagnosed patients had a relatively shorter duration of symptoms at their initial visit, and most presented late at night. Eighteen misdiagnosed patients (69.2%) initially visited the emergency department within 24 hours of onset of symptoms. Compared with patients diagnosed correctly on initial presentation, misdiagnosed patients had a significantly shorter hospital stay, fewer laboratory tests, and fewer physical findings of right lower quadrant tenderness, muscle guarding, rebound tenderness, fever, and migrating pain. Patients diagnosed late at night had a significantly shorter hospital stay and fewer abdominal ultrasound evaluations. On final presentation, initially misdiagnosed patients had a higher rate of appendiceal perforation than did correctly diagnosed patients. Misdiagnosed appendicitis is a problem in the emergency department. A shorter stay in the emergency department, fewer laboratory tests, less diagnostic imaging, and fewer physical findings may be responsible for misdiagnosed appendicitis late at night in the emergency department.


Relationships between developmental profiles and ambulatory ability in A follow-up study of preschool children with spastic quadriplegic cerebral palsy. To investigate the follow-up course of developmental profiles in preschool children with spastic quadriplegic (SQ) cerebral palsy (CP) who had varying ambulatory abilities. Forty-eight children with SQ CP between 1 and 5 years old were classified into 2 groups, the ambulatory and non-ambulatory groups, based on Gross Motor Function Classification System (GMFCS) levels during the initial assessment. The developmental profiles, consisting of development quotients (DQs) of 8 domains, were evaluated during the initial assessment and the final assessment one year later. The DQ change index (%) was calculated as 100% X (final DQ-initial DQ)/initial DQ. The DQs of all developmental domains in the non-ambulatory group were lower than those in the ambulatory group on both initial and final assessments (p<0.01). As indicated by the DQ change indices, most DQs in the ambulatory group decreased slightly, whereas those in the non-ambulatory group decreased considerably (p<0.05). Furthermore, fine motor function increased proportionally with age in the ambulatory group, but not in the non-ambulatory group. The DQs of the developmental profiles varied in preschool CP children with different ambulatory abilities. The course of developmental profiles in preschool children with SQ CP evolves with age and relates to the degree of ambulatory function. Knowledge of these developmental profiles may be helpful in understanding, predicting, and managing the developmental problems of these children.


The electromyographic responses of paraspinal muscles during isokinetic exercise in adolescents with idiopathic scoliosis with a Cobb's angle less than fifty degrees. Analysis of electromyographic (EMG) activities in the back during dynamic exercise is needed because more complex loading on the spine is created in comparison with that during static exercise. The purpose of this study is to investigate the difference in bilateral midback and low-back paraspinal muscle (PSM) activities during performance of different resistance isokinetic exercises in healthy subjects and those with scoliosis. Forty-one healthy subjects and thirty-three subjects with adolescent idiopathic scoliosis (AIS) were enrolled. An isokinetic back system in combination with quantitative surface EMG was used to evaluate the dominant and nondominant PSM activities by analyzing the root mean square (RMS) during isokinetic extension and flexion exercise at velocities of 30 degree/s and 90 degree/s. Significantly higher RMS of EMG were found in the dominant medial and lateral PSM of the lumbar region than the non-dominant muscles in the healthy control group and in those with AIS with smaller curves (<20 degrees) during isokinetic flexion and extension exercises. In AIS patients with larger curves (20 to 50 degrees), shifting of muscle activities from the dominant to the non-dominant side occurred during isokinetic exercises, and the EMG activities of the thoracic muscle were significantly higher on the non-dominant (concave) side than on the dominant (convex) side. The bilateral PSM do not act symmetrically during isokinetic back exercises. The dominant lumbar PSM supply the major action in healthy subjects and patients with small curve scoliosis. For larger curve scoliosis, compensated muscle activity is needed in the midback when doing resistance exercises. More midback protection may be needed by scoliotic subjects with large curves during resistance exercise.


Severe neuroleptic malignant syndrome: successful treatment with high-dose lorazepam and diazepam: a case report. Neuroleptic malignant syndrome (NMS) is an idiosyncratic and potentially fatal adverse complication of antipsychotic medications and other dopamine-modulating agents. It is characterized by hyperthermia, muscle rigidity, autonomic dysfunction and alteration in mental status. Here, we report a patient with severe NMS who was successfully treated with highdose lorazepam and diazepam. A 61-year-old man with bipolar I disorder was admitted to the hospital because of manic episodes. Fever, muscle rigidity, tachycardia, diaphoresis, elevated blood pressure and delirium occurred following intramuscular injection of haloperidol and NMS was diagnosed. Supportive treatment included hydration, alkalinized fluids and correction of abnormal electrolytes without the use of dantrolene, dopaminergic agents or electroconvulsive therapy. The Francis-Yacoub NMS rating scale was employed for evaluation of clinical improvement, and scores were 55 on the first day and 0 at discharge. The patient was followed up for 6 months and was free of NMS. In conclusion, this is the first report of rapid relief of NMS with high-dose lorazepam and diazepam in a Taiwanese patient.


Survival impact of initial surgical approach in stage I ovarian cancer. The aim of this study was to evaluate the impact on survival of initial laparoscopic surgery compared with conventional laparotomy in stage I epithelial ovarian cancer. We conducted a retrospective study which enrolled all consecutive patients with stage I epithelial ovarian cancer between January 1984 and December 2006. Patients with a histological diagnosis of epithelial ovarian cancer who underwent laparoscopy were recruited if their cases were compatible with stage I (clinical or surgical) at initial exploration. The independent samples t test, chi-square test, log-rank and Cox proportional hazards model were performed. A total of 208 patients were enrolled, including 34 patients with initial laparoscopy and 174 with laparotomy. The median follow-up time for survivors was 65 (range, 2-276) months. The 5-year overall survival (OS) and recurrence-free survival (RFS) rates were 67.4% and 69.5% in the laparoscopy group, and 88.7% and 78.7% in the laparotomy group, respectively. The median time to recurrence was 14.5 (range, 2-67) months. In multivariate analysis, the initial laparoscopy approach posted significant adverse impacts on the OS (laparoscopy vs laparotomy, the hazard ratio [HR]: 3.52, p=0.009) and the RFS (laparoscopy vs laparotomy, HR: 2.58, p=0.024), while a higher substage (stage IB-IC vs IA, HR: 8.29, p=0.040) was associated with only a worse OS, and its impact on the RFS was marginal. An initial laparoscopy intervention and higher substage posted significant adverse effects on the prognosis in stage I epithelial ovarian cancer. Important precautions when using laparoscopy for adnexal masses, such as avoiding rupture, applying protection, and submitting frozen sections, are recommended.


Operation cancellation at Chang Gung Memorial Hospital. Roughly 60,000 operations are performed at our medical center every year, so making efficient use of operating rooms (OR) is an important issue. Decreasing the cancellation rate of surgery is one method that could increase efficiency. We reviewed all OR cancellations in 2007 to survey the cancellation rates and causes. The present study was retrospective. Data were collected from the Department of Anesthesiology Quality Assurance Database of Chang Gung Memorial Hospital. We analyzed medical records for cancellations from January 1 to December 31, 2007. Data were analyzed using SPSS 16.0, employing descriptive measures and logistic regression. There were 61855 operations scheduled during this period; 229 were cancelled (0.37%). The mean age of patients in the cancelled group was significantly higher than that in the the non-cancelled group. We found a positive correlation between the cancellation rate and American Society of Anesthesiologists physical status. Cancellations for outpatient surgery were most frequent, as were those in the ophthalmology department. Forty-seven cases were cancelled because of cardiovascular problems; 136 operations were done later after the original cancellation issues were addressed while 11 were done under local anesthesia. Of all causes of cancellation of surgery, 54.1% were avoidable. Medical teams must communicate better with patients and relatives, identify and treat relevant comorbidities, and make adequate preparations for surgery.


The need for questionnaires in vascular surgery: the paradigm of carotid revascularization. A joint survey by the International Society for Vascular Surgery (ISVS) and the European Society for Vascular Surgery (ESVS).


Is the United States the core of the health care universe? Reflections of the recipient of the 2007-2008 E. J. Wylie Traveling Fellowship Award.


Microdialysis feasibility investigations with the non-hydrophilic antifungal voriconazole for potential applications in nonclinical and clinical settings. This study aimed at investigating the feasibility and validity of the microdialysis technique for the non-hydrophilic antifungal voriconazole, in settings for established concentric and new linear catheters. Optimal conditions for application of microdialysis in in vivo studies including steady-state conditions were to be elaborated. For in vitro microdialysis investigations, a robust and easy-to-handle system was developed permitting standardized physiological-like conditions. Various experiments on the influence of flow-rate (0.4 - 10.0 µl/min), voriconazole concentration (1.0 - 50.0 µg/ml) on relative recovery were performed. Additionally, the mass transfer coefficient r of voriconazole was estimated (WinNonlin™). In vitro microdialysis experiments suggested sufficient voriconazole concentrations in the dialysate for (non-)clinical investigations. The stability of voriconazole was confirmed over 10 h (37 °C). A flow-rate dependency was shown (optimum: 2.0 µl/min) and r was estimated to be 0.09 mm/min and 0.11 mm/min for concentric and linear catheters, respectively. Relative recovery in delivery/recovery experiments was independent of the voriconazole concentration ranging from 96.0% to 97.8%/93.8% to 100.2% (CV 1.7%/ 0.5%) indicating unhampered passage of voriconazole through the catheter. Investigations mimicking steady-state suggested voriconazole concentration of 100 - 200 µg/ml for in vivo catheter calibration solutions. The results demonstrate the feasibility and validity of the microdialysis technique in clinically-mimicked settings despite the higher lipophilicity of voriconazole and support the application of the technique in vivo.


Management of the immature autogenous arteriovenous fistula. A high-quality autogenous arteriovenous fistula provides the optimal access for hemodialysis. Following initial surgical construction of a fistula, the maturation process is driven by hemodynamic, cellular, and humoral factors that must result in increased blood flow, vessel dilation, and thickening of the vessel wall before the fistula can be successfully used for dialysis needle access. Different demands are placed on each fistula depending on the individual patient's hemodialysis requirements, which must be clearly understood to properly assess and treat the immature fistula. When spontaneous maturation fails to achieve a functional fistula, additional surgical or minimally invasive interventional procedures may be necessary to enhance the maturation process. Various techniques have been reported to achieve successful fistula maturation. The purpose of this article is to review the concepts of fistula maturation and the interventions that may be performed in cases where there is failure to mature spontaneously.


Sources and predictors of home-kept prescription drugs. To examine the extent of home-kept prescription drugs in the general population and to identify the predictors for a higher number of prescription drugs kept in people's homes. The study included a random stratified sample of 1,000 Slovenian inhabitants. Participants answered a self-administered questionnaire regarding sources and contents of their home pharmacies. The main outcome measure was the presence and the number of home-kept prescription drugs. The response rate was 41%. At least one prescription drug in the home pharmacy was kept by 298 (75.4%) of the respondents, average number of prescription drugs was 3.1 ± 3.3. The majority of the respondents (319, 77.8%) bought the drugs for self-medication in pharmacies. Almost a quarter of the respondents obtained them from relatives and friends (82, 20.0%). Multivariate logistic regression analysis showed that a visit to a clinical specialist in the previous year and high blood pressure were independent predictors for the presence of any home-kept prescription drug. Multivariate linear regression analysis also showed that rural and suburban living areas, a visit to a clinical specialist, a need for a home visit by a doctor in the past year, and the presence of diabetes, high blood pressure, asthma or depression are independent predictors for a higher number of home-kept prescription drugs. Doctors have to take into account that their patients keep several prescription drugs in their home pharmacies. These patients are potential providers to their friends and relatives of potentially unsafe drugs for self-medication.


Technique of adding a diameter-reducing wire to the modified TX2 fenestrated stent graft. One of the technical limitations of surgeon-modified fenestrated stent grafts is the lack of a diameter-reducing wire, which facilitates catheterization of target branches if there are errors of device design, alignment, or implantation. This article describes a technique of adding a diameter-reducing wire to the modified TX2 fenestrated stent graft for compassionate use in aortic emergencies or high-risk patients who do not have access to manufactured devices. The modified Cook TX2 stent graft was created using reinforced fenestrations with gold nitinol markers. After the TX2 stent was fully unsheathed, one of the nitinol wires located in the inner cannula was withdrawn and redirected externally through and through the fabric of the stent graft. Each Z stent was constrained using the nitinol wire for support and two nonlocking polypropylene loops. The use of a diameter-reducing wire facilitates side branch catheterization by allowing longitudinal and rotational movement to the modified fenestrated stent graft in patients where there is misalignment between the fenestration and the origin of the target vessel.


Transit-time volume flow measurements in autogenous femorodistal bypass surgery for intraoperative quality control. The aim of this study was to assess intraoperative transit-time volume flow measurements (VFMs) as a tool for intraoperative evaluation of lower extremity arterial bypass grafts and to predict their patency. We analyzed 273 consecutive patients who had an infrainguinal bypass procedure using the great saphenous vein from 1998 until 2008; 103 had an intraoperative VFM. All intraoperative revisions were recorded and analyzed. Patency and revision rates were compared between those receiving and those not receiving intraoperative VFM. Cox regression was used for analysis of predictors of patency. Primary patency at 1 and 2 years was 75 and 67%, respectively, in patients receiving intraoperative VFM versus 72 and 69% in those without VFM (p  =  .79). In the VFM group, 12% had an immediate revision versus 6% without VFM (p  =  .06). In the VFM group, 4% underwent revision to salvage the bypass within the first postoperative 30 days versus 6% without VFM (p  =  .32). Patency was not associated with the use of VFM. Receiver operating characteristic curve was significant for occlusion at 30 days postoperatively but with a low predictive value (p  =  .019,area under the curve 0.648). VFM may be helpful in selecting bypasses requiring immediate revision to prevent postoperative occlusion. The use of VFM is not significantly associated with patency.


Staged hybrid repair of thoracoabdominal aortic aneurysm after chronic type B aortic dissection. The purpose of this study was to evaluate clinical outcomes of combined endovascular and open techniques to eradicate false lumen dilatation in the visceral aortic segment after type B aortic dissection associated with aortic aneurysm. We reviewed eight patients with distal thoracic and abdominal false lumen dilatation treated with a staged procedure. These included arch debranching as needed, proximal thoracic endovascular repair, and open surgical correction with abdominal aortic replacement of the visceral and infrarenal aorta. False lumen eradication was successful in all patients. There were no operative deaths, and paraplegia or paraparesis occurred in two patients. During a mean follow-up of 30 months, no complications or secondary interventions were necessary. The thoracic false lumen remained thrombosed in all patients, with no evidence of aortic dilatation or stent graft complications. Complete thrombosis and eradication of the false lumen can be achieved through a three-stage repair of chronic type B aortic dissection with aneurysmal dilatation. A prospective randomized trial is needed to establish the viability of this approach versus standard open repair of type II thoracoabdominal aortic aneurysms.


Imaging inflammation in stroke using magnetic resonance imaging. Stroke is the third leading cause of death, after myocardial infarction and cancer, and the leading cause of permanent disability in Western countries. Although anti-inflammatory drugs have shown very promising results in preclinical rodent studies, they appeared to be ineffective against stroke in clinical trials. In this context, non-invasive detection of inflammatory cells after brain ischemia could be helpful (i) to select patients who may benefit from anti-inflammatory treatment, and/or (ii) to target an adequate individualized therapeutic time window. Magnetic resonance imaging (MRI) coupled with injection of iron oxide nanoparticles, a contrast agent taken up by macrophages ex vivo and in vivo, appears to be a promising tool for this purpose. This review focuses on the use of this technique to image inflammation in pre-clinical and clinical studies of stroke. Despite current limitations, MRI of inflammation may become an important tool for the investigation of novel ischemic stroke therapeutics targeting inflammation.


Pharmacokinetic and tolerability profile of once-daily zibotentan (ZD4054) in Japanese and Caucasian patients with hormone-resistant prostate cancer. To investigate potential differences in zibotentan pharmacokinetics between Japanese and Caucasian patients with hormone-resistant prostate cancer (HRPC) following single and multiple dosing. In the Japanese study, 18 patients received a single dose of zibotentan 5, 10 or 15 mg followed by 72 h washout before 26 days' once-daily dosing. In the Caucasian study, 21 patients received a single dose of zibotentan 5, 10 or 15 mg followed by 72 h washout before 12 days' once-daily dosing. Pharmacokinetic parameters were similar between populations. Absorption of zibotentan was rapid with maximum plasma concentrations typically achieved within 3 h of dosing. Mean clearance, 17.9 and 18.7 ml/min in Japanese and Caucasian patients, respectively (range 7.0 - 36.3 ml/min in Japanese patients and 7.8 - 29.5 ml/min in Caucasian patients) and volume of distribution, 14.0 and 15.6 l for Japanese and Caucasian patients, respectively (range 7.9 - 29.1 l in Japanese patients and 9.6 - 23.8 l in Caucasian patients) were relatively low, and t1/2 was approximately 12 h (range 5.7 - 18.8 h in Japanese patients and 5.0 - 22.9 h in Caucasian patients) following single dosing. Little accumulation was observed following daily dosing and multiple-dose pharmacokinetics were predictable. Exposure levels achieved in some Japanese patients receiving zibotentan 15 mg were higher than those observed in Caucasian patients, however, this may be due to differences in body weight, as exposure levels were similar when data were normalized for body weight. Zibotentan was well tolerated in both populations. There are no clinically relevant differences in the disposition and pharmacokinetics of zibotentan between Japanese and Caucasian patients with HRPC.


Initial results of a 12-week, institution-based, supervised exercise rehabilitation program for the management of peripheral arterial disease. This study assessed the effectiveness of a 12-week, institution-based, supervised exercise rehabilitation program with atherogenic risk factor modification in improving cardiovascular profile, ambulatory function, and quality of life of patients with peripheral arterial disease (PAD) by comparing pre- and postprogram measurements. Participants were prospectively enrolled. Cardiovascular profile variables, ambulatory function tests, and quality of life questionnaires were evaluated. Of 101 institution-based program participants, 69 completed the 12-session minimum and 47 completed a postprogram evaluation. Mean postprogram results were significantly different from preprogram results, corresponding to improvement, for the following variables: triglyceride levels (p  =  .036), both function tests (p < .001 for both), four of five Walking Impairment Questionnaire measurements, and Intermittent Claudication Questionnaire score (p  = .001). This supervised exercise program improved the cardiovascular profiles, ambulatory function, and quality of life of PAD patients completing the program and is a viable adjunct to drug therapy and surgical intervention.


Co-prescription of gastroprotective agents in patients taking non-selective NSAIDs or COX-2 selective inhibitors: analysis of prescriptions. To evaluate the prevalence of co-prescription of GPAs (proton pump inhibitors - PPIs and H2-receptor antagonists) and non-selective NSAIDs or COXIBs in patients registered under the local health authority (LHA) of Bergamo, a city in the north of Italy. A drug utilization analysis was done using the Bergamo prescription Health Services Electronic Database. All patients aged 35 years or older who had received at least one prescription during 2004 for non-selective NSAIDs and/or COXIBs were divided into three groups: occasional, chronic and new users. Among chronic users, 44.8% were treated with non-selective NSAIDs, 11.6% with COXIBs, and 43.6% with both (mixed NSAIDs). For new users, non-selective NSAIDs were prescribed to 82.7%, COXIBs and mixed NSAIDs to 10.8% and 6.5%. PPIs were co-prescribed to 7.1% of COXIB users and 5.8% of non-selective NSAID occasional users. Among chronic users, the figures were 15.6% and 14%. For new users, prescriptions for COXIBs were associated with less use of GPA for patients who received the first and last prescription for NSAIDs and GPAs on the same day, while for patients who became chronic users COXIBs did not reduce the probability of co-prescription of a GPA: the number of co-prescribed medications and antithrombotics or corticosteroids were independent predictors of GPA use. COXIBs seem to be used in patients at high risk of GI toxicity. However, the fear of GI adverse reactions and the uncertain safety profile of COXIBs leads many physicians to boost the gastroprotection by prescribing a PPI.


Percutaneous in situ oxygenated pump perfusion of a transplanted kidney during abdominal aortic aneurysm repair. The surgical management of aortic aneurysms in kidney transplant patients is a difficult clinical scenario where preservation of the kidney allograft during aortic cross-clamping is paramount. We describe a novel technique for renal protection during abdominal aortic aneurysm repair with in situ oxygenated pump perfusion of the transplanted kidney. A percutaneous approach is used for common femoral artery and vein cannulation and a cardiopulmonary bypass circuit to provide retrograde oxygenated pump perfusion to the transplanted kidney. This technique allows adequate kidney perfusion during warm ischemia and minimizes morbidity by using a percutaneous access technique.


Associations between oxaliplatin-induced peripheral neuropathy and polymorphisms of the ERCC1 and GSTP1 genes. Oxaliplatin-induced chronic neuropathy is cumulative and dose-limiting; reliable predictors and determination of the mechanism of this toxic effect are needed. We retrospectively studied 51 Japanese adults with colorectal cancer who had received oxaliplatin-based chemotherapy to explore the pharmacogenetic association between oxaliplatin-induced neuropathy and polymorphisms of the excision repair cross-complementation Group 1 (ERCC1) and glutathione-S-transferases pi 1 (GSTP1) genes. For the ERCC1 C118T polymorphism, Grade 1 chronic neuropathy developed earlier in patients with C/T and T/T genotypes (median number of treatment cycles at onset = 6) than in those with the reference C/C genotype (7 cycles; p = 0.0162 by the generalized Wilcoxon test). For the GSTP1 Ile105Val polymorphism, chronic neuropathy developed earlier in patients with the reference Ile/Ile genotype (6 cycles) than in those with Ile/Val and Val/Val genotypes (9 cycles; p = 0.0321). ERCC1 C118T and GSTP1 Ile105Val polymorphisms were not significantly associated with an increased risk of developing Grade 2 or more severe chronic neuropathy. Our results suggest that ERCC1, C118T and GSTP1 Ile105Val polymorphisms are more strongly related to the time until onset of neuropathy than to the grade of neuropathy. Most likely these polymorphisms influence patients' sensitivity to neuropathy.


Combined endovascular and vascular surgical therapy of a blister-like distal internal carotid aneurysm in a patient with a right-sided aortic arch. Blood blister-like aneurysms (BBAs) are rare but challenging to treat owing to their fragile, thin walls and poorly defined necks. A right-sided aortic arch is an uncommon congenital cardiac anomaly with an estimated incidence of only 0.1% and presents a challenge to intubation at vessels above the aortic arch. This represents an extremely rare case of a BBA at the left internal carotid artery with a right-sided aortic arch treated with combined endovascular and vascular surgical therapy. We report the case and provide a short review of the relevant literature.


Extracranial internal carotid artery pseudoaneurysms after kinking reconstruction. The purpose of this report is to describe our experience of infected false aneurysm treatment following internal carotid artery (ICA) reconstruction. Five and 6 years before admission, bilateral reconstruction was done because of ICA kinking at a local health center. The patient was symptomless for 5 years but later became partially symptomatic (dizziness, vertigo, and visibly bilateral neck pulsatile masses). On routinely performed ultrasonography and multislice scanner examinations, the bilateral ICA pseudoaneurysms were revealed. The final treatment was surgery and aneurysmal sac resection followed by end-to-end arterial reconstruction. A right-sided wound swab was positive; Staphylococcus aureus was cultured. Antibiotics were administered: teicoplanin (Targocid) 800 mg as an initial dose followed by 400 mg maintenance doses over the following 4 days. After 1 month, left ICA reconstruction was done and a wound swab showed staphylococcal infection as well. At the 12-month follow-up, the patient was doing well; cerebral vascularization was well preserved. Infected false aneurysms are rare complications following carotid artery reconstruction. Aneurysmal sac resection and arterial reconstruction with end-to-end anastomosis or autologous saphenous vein are recommended. A wound swab is mandatory.


Effects of probenecid on the pharmacokinetics of mizoribine and co-administration of the two drugs in patients with nephrotic syndrome. Probenecid (PRB) is an agent that reduces the systemic level of uric acid, and has the ability to inhibit the renal tubular secretion of agents that are co-administered with it. In this study, we evaluated the effects of PRB co-administered with mizoribine (MZR) on the pharmacokinetics (PK) of MZR in 12 patients with nephrotic syndrome. The elimination rate constant (kel) was used as an indicator of changes in the PK of MZR when the secretion of MZR was inhibited by co-administration of PRB, in order to determine the extent to which MZR was influenced by PRB. In 4 of the 12 patients studied, kel decreased and the biological half-life (t1/2) of MZR was prolonged when co-administered with PRB, in comparison with the values when MZR was used alone, thus revealing that the PK of MZR was influenced by PRB. Co-administration of PRB with MZR appears to be effective in prolonging the biological half-life of MZR and enhancing its effect in patients with nephrotic syndrome, although further studies will be required to determine the optimal dosage of PRB and renoprotective effects.


Pharmacokinetic study of the oral administration of procaterol hydrochloride hydrate 50 µg in healthy adult Japanese men. The pharmacokinetics of procaterol, a selective beta2-adrenergic agonist with a high intrinsic efficacy in man, could not be determined in humans when the drug was launched because of the low therapeutic dose and the low sensitivity of the analytical methods available at the time. However, a recently established analytical method using LC-MS/MS has been refined to enable the determination of the pharmacokinetic profile of procaterol and its metabolites in humans. Procaterol hydrochloride hydrate 50 µg was administered orally to 8 healthy adult Japanese men. Plasma and urine samples collected from the subjects were analyzed by use of LC-MS/MS for procaterol and its metabolites. Following the oral administration of procaterol hydrochloride hydrate 50 µg, the plasma concentration of procaterol reached a Cmax of 136.4 pg/ml at ~1.44 h post-dose. The mean apparent terminal elimination half-life was ~3.83 h. DM-251 and DM-252, glucuronides of the optical isomers of procaterol, were the main metabolites and both were present in plasma at higher levels than procaterol in the plasma. The 24 h urinary excretion rates of unchanged procaterol, DM-251 and DM-252 were 15.7%, 12.4% and 11.2% of the procaterol administered, respectively. This study describes the pharmacokinetic profiles of procaterol and its metabolites following the oral administration of procaterol hydrochloride hydrate 50 µg. Procaterol and its glucuronides were found at high levels in the plasma and urine.


Different persistence on initial basal supported oral therapy in Type 2 diabetics is associated with unequal distributions of insulin treatment regimens under real-life conditions in Germany. Results from a representative German database and from two German health services research studies revealed an unequal distribution between basal supported oral therapy (BOT) and basal-bolus therapy (ICT) regimens in Type 2 diabetics treated with either insulin glargine (GLA) or human insulin (Neutral Protamine Hagedorn; NPH). This study assesses whether this unequal distribution could be caused by a different persistence on the initial BOT regimen. A Markov model was developed simulating the transition from BOT to ICT during a treatment course of 10 years. Data on persistence with BOT were obtained from the IMS® Disease Analyzer database. The model cohort consisted of German statutorily insured Type 2 diabetics starting a BOT either with insulin glargine or NPH insulin at a ratio of 1 : 1. The number of Type 2 diabetics who switched from BOT to ICT differed between the two groups: After 2 years, 53% of glargine-treated patients and 31% of NPH-treated patients continued the BOT. After 6.5 years, all NPH-treated patients had switched to ICT. However, complete transition to ICT of glargine-treated patients occurred 1.75 years later. In the first quarter of Year 3, the model simulation resulted in BOT : ICT ratios comparable to those found in the real-world settings for GLA- and NPH-treated patients. The simulation indicates that the persistence on the initial basal supported oral therapy is associated with the resulting BOT : ICT ratio. Therefore, the unequal distribution between BOT and ICT of Type 2 diabetics treated with either insulin glargine or NPH insulin might be caused by different persistence on the initial BOT regimen.


Night-time bioavailability of levodopa/carbidopa/entacapone is higher compared to controlled-release levodopa/carbidopa. Controlled-release levodopa/carbidopa (CR-LC) is often used to provide prolonged control of night-time motor symptoms in patients with Parkinson's disease (PD). Levodopa/carbidopa/entacapone (LCE) provides higher bioavailability of levodopa compared with levodopa/carbidopa formulations and has been shown to be effective in PD patients with wearing-off symptoms. The aim of this study was to compare the bioavailability of levodopa after a single evening dose (administered at 10 p.m.) of LCE 200 or CR-LC 200. This was an open-label, randomized, crossover study in healthy subjects. The main pharmacokinetic (PK) parameters were AUC, Cmax, C6h and t1/2 of levodopa. A single evening dose of LCE 200 was associated with significantly better bioavailability compared with CR-LC 200. In line with increased bioavailability of levodopa, LCE 200 induced more nausea. The results of this study demonstrate that a single bedtime dose of LCE 200 provides higher bioavailability of levodopa compared to CR-LC 200.


Factors influencing valproate pharmacokinetics in children and adults. The aim of the present study was to build population pharmacokinetic models for the clearance of valproate (VPA) in 2 separate populations of Serbian patients with epilepsy, children and adults. Analysis was performed using 65 and 63 steady-state concentrations of VPA collected from 58 children and 60 adult epileptic patients, respectively. Mean values for total body weight and age were 27.07 ± 13.08 kg and 7.21 ± 3.63 years in the pediatric population, and 69.67 ± 15.60 kg and 33.97 ± 16.41 years in the adult population. The one-compartment model with first order elimination and without absorption was used from the PREDPP (Prediction for Observation Population Pharmacokinetics) library of NONMEM software. The derived final models show that VPA clearance increased with total body weight of patients in both populations. However, the carbamazepine comedication was the main determinant of the final model in children whereas phenobarbitone comedication was the most important factor in the adult population. The magnitudes of these effects were +0.159 lh-1 and +0.539 lh-1 for carbamazepine and phenobarbitone, respectively. A significant decrease in interindividual and intraindividual variability was observed in the target populations. The pharmacokinetic models obtained were validated in groups of 15 epileptic patients, each showing good predictive performance of the model. The derived models describe well VPA clearance in terms of characteristics of Serbian pediatric and adult epileptic patients, offering a basis for rational individualization of VPA dosage regimens.


Stroke after treatment with bortezomib and dexamethasone in a Chinese patient with extramedullary relapse of multiple myeloma. Thromboembolic complications commonly occur in patients with multiple myeloma (MM). The risk of such complications may be elevated by the use of immunomodulatory agents such as thalidomide and lenalidomide as initial therapy for MM. However, arterial thrombosis after treatment with bortezomib is rare. Herein we report a case of a 70-year-old Chinese male patient with extramedullary relapse of MM. After treatment with bortezomib and dexamethasone he developed a nonfatal thrombotic stroke. Administration of bortezomib and dexamethasone was then discontinued and he obtained partial remission.


Erythropoietin production by distal nephron in normal and familial amyloidotic adult human kidneys. the kidney is the major site of erythropoietin production. Many efforts have been made to identify renal erythropoietin-producing cells. Previous studies showed conflicting results, but the predominant localization reported was the peritubular interstitial and tubular epithelial cells. This study was conducted to identify the erythropoietin-producing cells in renal biopsies from 10 cadaveric donors and 45 patients with familial amyloidosis ATTR V30M, thirteen of them with anemia. Familial amyloidosis Type I (FAP-I) is a genetic disorder caused by a transthyretin (TTR) protein variant presenting a single amino acid substitution of methionine for valine at position 30 of the polypeptide chain (TTR V30M). Anemia in FAP-I is associated with inappropriately low serum erythropoietin levels. erythropoietin expression was detected by in situ hybridization (ISH) and confirmed by laser capture microdissection followed by PCR. Renal segments were identified by immunohistochemistry. erythropoietin was mainly expressed by epithelial distal tubular cells and collecting tubules and additionally, in a few biopsies, by glomerular cells. A similar expression pattern was observed in donors and FAP-I patients. No increased mRNA erythropoietin expression was found in anemic patients, all of them presenting only a slight expression in medulla and cortex. these results suggest the distal nephron as the major site of erythropoietin production, and support the notion that an inappropriate erythropoietin production is the cause of anemia in familial amyloidosis ATTR V30M.


Nutritional markers, not markers of bone turnover, are related predictors of bone mineral density in chronic peritoneal dialysis patients. this study evaluated the factors associated with bone mineral density (BMD) in chronic peritoneal dialysis (CPD) patients. in this cross-sectional study in 91 stable CPD patients, BMD was measured using dual-energy X-ray absorptiometry. Markers of bone turnover (iPTH, osteocalcin, bone alkaline phosphatase, serum C-telopeptide), 25-hydroxy (OH) vitamin D3 and nutritional markers (prealbumin, nPNA, BMI) were measured by standard techniques. of the 91 patients, 48 were female and 22 (24%) had Type 2 diabetes. Mean age of the patients was 52.7, and patients had been on PD for about 44 months. For the lumbar spine (LS) and femoral neck (FN), the mean T-scores were -1.19 ± 1.53 and -1.24 ± 1.01, respectively, and the mean Z-scores were -0.78 ± 1.33 and -0.40 ± 0.92, respectively. Using the WHO-based criteria, osteopenia (-2.5 < T-score < -1.0) at the LS and FN was observed in 37 (41%) and 48 (53%) patients, respectively, and osteoporosis (T-score <= -2.5) at the LS and FN was observed in 15 (17%) and 6 (7%) patients, respectively. LS T-score was positively correlated with BMI (r = 0.40, p < 0.001) and albumin (r = 0.29, p = 0.005), and FN T-score was positively correlated with albumin (r = 0.40, p < 0.001), prealbumin (r = 0.38, p < 0.001), age (r = -0.32, p = 0.002) and BMI (r = 0.29, p < 0.006). Markers of bone turnover were not associated with BMD. In multiple linear regression models, independent predictors of FN T-score were age, BMI, albumin and prealbumin (r(2) = 0.259, F = 6.23, p < 0.001), whereas BMI was the only independent predictor of LS T-score (r(2) = 0.24, F = 6.63, p < 0.001). nutritional markers, not markers of bone turnover, are correlated predictors of BMD in CPD patients.


Relationship between carnosinase gene CNDP1 leucine repeat polymorphism and the clinical outcome of Chinese PD patients. pre-clinical studies showed that carnosine may have a beneficial cardiovascular effect. We studied the effect of tri-nucleotide repeat (CTGs) polymorphisms in exon 2 of the CNDP1 gene, which codes for carnosinase and is responsible for the degradation of carnosine, on the clinical outcome of Chinese peritoneal dialysis (PD) patients. we studied 442 PD subjects. Genotyping was done by direct sequencing of genomic DNA. Patients were followed for 43.5 ± 16.2 months. the prevalence of 6-6, 5-6, 5-5 and 4-6 CTGs genotypes was 80.3%, 18.6%, 0.9% and 0.2%, respectively. A total of 270 patients (61.1%) developed the primary composite end point during follow-up. The 5-year event-free survival of the 6-6 CTGs and non 6-6 group was 37.1% and 21.3%, respectively (log rank test, p = 0.3). the CTGs polymorphism of the CNDP1 gene does not affect survival of Chinese PD subjects. The role of carnosine and CNDP1 gene polymorphism in the pathogenesis of cardiovascular disease requires further study.


Hemodialysis patients' experience with and attitudes toward the buttonhole technique for arteriovenous fistula cannulation. the buttonhole technique for arteriovenous fistula cannulation has been recommended as an alternative to the rope ladder technique. we compared patients' experiences and hypothesized that patients would prefer the buttonhole technique. in an observational cross-sectional study using a 23-item questionnaire, we surveyed hemodialysis patients at 3 dialysis centers who had previously used the rope ladder technique and were presently using the buttonhole technique for their experiences with and attitudes toward the two techniques. Twelve months later, patients' attitudes were reassessed. 26 patients met inclusion criteria. On a scale of 0 (not at all satisfied) to 10 (very satisfied), patients reported a mean satisfaction with the buttonhole technique of 8.5 ± 1.9. 96% of patients said they would recommend it, and 83% reported that the buttonhole technique was easier for the nurses to use. Fewer patients reported fistula infiltration with the buttonhole technique (12% vs. 59%, p = 0.008). Twelve months later, 18 of 23 patients (78%) still dialyzing in the study units remained satisfied with the buttonhole technique. patients reported a high level of satisfaction, fewer complications, and a positive attitude about suggesting the buttonhole technique to other patients. Our findings support the recommendation for its more widespread use.


A single-center experience of preemptive anticoagulation for patients with risk factors for allograft thrombosis in renal transplantation. to review our single-center experience of preemptive anticoagulation for the prevention of allograft thrombosis in patients with hypercoagulable states. this is a retrospective cohort study. Included subjects were first-time kidney allograft recipients transplanted between 2003 and 2007 at a single center, with hypercoagulable states: prior venous thromboembolism, multiple vascular access thromboses, or identifiable thrombophilia. The predictor variable was preemptive anticoagulation and outcome variable was allograft thrombosis. Other risk factors for allograft thrombosis, characteristics of transplantation, and hemorrhagic complications were also examined. among this high-risk cohort (n = 48), 16 received preemptive anticoagulation and 32 did not. The anticoagulated group included significantly more subjects with identifiable thrombophilia (50.0% vs. 0%; p < 0.001). One subject (6.3%) in the anticoagulated group and 6 (18.8%) without anticoagulation developed allograft thrombosis (p = 0.40). A perinephric hematoma was observed in 5 (31.3%) and 2 (6.3%) with and without anticoagulation, respectively (p = 0.03). preemptive anticoagulation was associated with a non-significant trend towards decreased allograft thrombosis. It may be associated with increased risk of hemorrhage and should be considered cautiously in high-risk patients.


Comparison of estimated glomerular filtration rate (eGFR) using the MDRD and CKD-EPI equations for CKD screening in a large population. recently, the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) proposed a new equation for estimating glomerular filtration rate (eGFR), which could potentially replace the Modified Diet for Renal Disease Study (MDRD) equation in routine clinical use. Our aim was to evaluate the correlation between them and to compare the prevalence of each CKD stage using these two equations. we measured serum creatinine in 38,188 consecutive patients and calculated eGFR using the CKD-EPI and MDRD equations. We also compared the distribution of CKD stages for both equations. there was very good correlation between eGFR estimated by CKD-EPI and MDRD at values < 60 ml/min × 1.73 m2, but not at higher values. Estimated prevalence of CKD (eGFR < 60 ml/min × 1.73 m2) was 5.9% with CKD-EPI and 7.5% with MDRD. Furthermore, the prevalence of CKD Stage 2 was lower with CKD-EPI (33.8% vs. 49.1%. with MDRD). the use of the CKD-EPI equation results in a lower estimated prevalence of CKD, compared to the MDRD equation. This may have important implications for public health and clinical practice, as well as for future modification of guidelines for laboratories.


The changing pattern of primary glomerulonephritis in Singapore and other countries over the past 3 decades. This review of 2,586 renal biopsies over the past 3 decades in Singapore documents the changing pattern of glomerulonephritis (GN) from that of a third world country to that of a developed nation. In the 1st decade, mesangial proliferative glomerulonephritis was the most common form of primary GN, just as it was in the surrounding Asian countries. In the 2nd decade, the prevalence of mesangial proliferative GN decreased with a rise in membranous, GN which is also seen in China and Thailand. In the 3rd decade, there was a dramatic increase in focal sclerosing glomerulosclerosis. This increase reflects aging and obesity in keeping with more developed countries like Australia, India, Thailand and the United States of America. IgA nephritis remains the most common GN. Apart from the geographical influence, other socioeconomic factors play a significant role in the evolution of the renal biopsy pattern. Mesangial proliferative GN remains prevalent in many Asian countries, but in Singapore the prevalence is decreasing just as it is in Japan, Korea and Malaysia. Worldwide, the prevalence of focal sclerosing glomerulosclerosis continues to increase in many countries.


Gastrointestinal sensitivity to soy and milk proteins in patients with IgA nephropathy. sensitivity to food antigens has been postulated as a contributing factor to the pathogenesis of IgA nephropathy (IgAN). in this study we used a recently developed mucosal patch technique to evaluate rectal mucosal sensitivity to soy and cow's milk (CM) proteins in IgAN patients (n = 28) compared to healthy subjects (n = 18). The rectal mucosal production of nitric oxide (NO) and release of myeloperoxidase (MPO) and eosinophil cationic protein (ECP) were measured. Serum samples were analyzed for IgA and IgG antibodies to alpha-lactalbumin, beta-lactoglobulin, casein and soy. 14 of 28 (14/28) patients experienced a rectal mucosal reaction, measured by increased NO and/or MPO levels, upon rectal challenge with soy and/or cow's milk proteins. The levels of IgG antibodies to alpha-lactalbumin, beta-lactoglobulin and casein were significantly higher in CM sensitive as compared with non-sensitive IgAN patients, whereas the mean serum levels of IgA antibodies were similar. No differences were seen in serum levels of IgA or IgG antibodies to soy. it is concluded that approximately half of our IgAN patients have a rectal mucosal sensitivity to soy or CM, and that an immune reactivity against antigens may be involved in the pathogenesis of IgAN in this subgroup of patients.


Resolution of mesangial light chain deposits 3 years after high-dose melphalan with autologous peripheral blood stem cell transplantation. A 52-year-old woman was admitted to our hospital for treatment of nephrotic syndrome. Funduscopic findings showed fundal hemorrhage and soft exudates, and serologic analysis showed a monoclonal serum component that was identified as Bence Jones protein-k type. A bone marrow biopsy showed diffuse proliferation of atypical plasma cells, while a renal biopsy showed diffuse and nodular mesangial proliferation. Immunohistochemical staining confirmed the presence of k chains along the glomerular basement membrane and in mesangial areas. The patient was diagnosed as multiple myeloma (Bence Jones k type) with light chain deposition disease (LCDD). After high-dose melphalan and autologous peripheral blood stem cell transplantation (PBSCT), the multiple myeloma and nephrotic syndrome were in complete remission; her renal function was improved, but a renal biopsy performed 6 months after PBSCT showed the persistence of diffuse and nodular lesions. By contrast, a renal biopsy performed 3 years later showed complete resolution of the diffuse and nodular mesangial proliferation.


Acute neurological presentation due to copper deficiency in a hemodialysis patient following gastric bypass surgery. Acquired copper deficiency has been recently recognized as a cause of myelopathy, and has been reported to occur many years after gastric bypass surgery performed to aid weight reduction in morbidly obese patients. We report a case of a young woman treated by hemodialysis who presented with acute neurological symptoms 5 months after gastric bypass surgery for severe obesity. She had symptoms and signs of cerebellar, spinal cord and peripheral nerve disease, which improved following parenteral copper supplementation. Now that gastric bypass surgery is being offered to morbidly obese hemodialysis patients, this case highlights the importance of monitoring copper levels in hemodialysis patients following gastric bypass surgery.


Histopathological manifestations of membranoproliferative glomerulonephritis and glomerular expression of plasmalemmal vesicle-associated protein-1 in a patient with polycythemia vera. Only a few cases of various glomerulonephropathies have been reported in patients with polycythemia vera. We report the case of a 72-year-old female with polycythemia vera in whom renal biopsy examination showed membranoproliferative glomerulonephritis (MPGN)-like lesion and glomerular expression of plasmalemmal vesicle-associated protein-1 (PV-1), a marker of glomerular capillary remodeling after injury. Prior to admission to our hospital for nephrotic syndrome, she had received hydroxyurea and phlebotomy. On admission, she was hypertensive with pretibial edema, hepatosplenomegaly, massive proteinuria (6.14 g/day), low serum albumin (2.9 g/dl), high fibrinogen, fibrin/fibrinogen degradation products and thrombomodulin levels, but with normal serum creatinine and complement levels. Microscopic examination of a renal biopsy demonstrated MPGN-like features with double contour and mesangial interposition. Electron microscopy showed subendothelial deposits, platelets attached to glomerular capillary walls and fibrin deposition. Immunofluorescence study identified IgM deposition along part of the capillary wall and mesangium. CD42b-positive platelets and megakaryocytes were detected in glomerular capillaries, accompanied with increased expression of platelet-derived growth factor receptor b and thrombomodulin in the mesangium and glomerular capillary, respectively. PV-1 was expressed along the glomerular capillary. Anti-platelet and anticoagulant combination therapy, together with the use of anti-hypertensive agents and hydroxyurea, resulted in improvement of the nephrotic syndrome. The findings suggested that activated platelets, enhanced coagulation state and endothelial damage may contribute to glomerulonephropathy associated with polycythemia vera.


An 8-month-old boy with congenital fibromuscular dysplasia presenting with shock caused by sudden renal hemorrhage. Fibromuscular dysplasia (FMD) is a non-atheromatous, non-inflammatory, multifocal segmental angiopathy. FMD is the most common cause of pediatric renovascular hypertension. Aneurysmal formation of the main renal artery and distal branches is a rare complication of FMD in infancy. We report an 8-month-old boy with FMD presenting with shock caused by sudden renal hemorrhage that necessitated removal of one kidney. A diagnosis of renovascular hypertension resulting from intimal type FMD with aneurysmal formation was made on the basis of the presence of hypertension, elevation of PRA and aldosterone activity, pathological findings and the results of renal angiography. Our findings suggest that it is therefore necessary to consider FMD with aneurysmal formation as a possible cause of hypertension and renal hemorrhage in infants.


Prevalence of the antiheparin-platelet factor 4 antibody in hemodialysis (HD) patients and its effects upon dialysis access.


CKD in disadvantaged populations: the uncomfortable realities.


Pseudoaldosteronism with increased serum cortisol associated with pneumonia, hypouricemia, hypocalcemia, and hypophosphatemia. We describe here the interesting case of a 73-year-old hypertensive man with pseudoaldosteronism. He had been taking glycyrrhizin at a dose of 75 mg/day for 12 years because of mild liver damage, but had never experienced any previous symptoms associated with hypokalemia. He was referred to our hospital because of hypokalemic tetraparesis and rhabdomyolysis. At that time, we noted mineralocorticoid excess characterized by hypokalemia due to urinary K loss, exacerbation of hypertension due to increased tubular Na reabsorption, metabolic alkalosis, and suppression of both plasma renin activity and plasma aldosterone concentration. His urinary free cortisol excretion rate and the urinary ratio of free cortisol to free cortisone were markedly elevated. Thus we diagnosed pseudoaldosteronism that was related to the long-term use of glycyrrhizin. When he developed pseudoaldosteronism, he also contracted pneumonia, and exhibited elevated levels of serum cortisol and creatinine clearance (CCr) as well as hypouricemia, hypocalcemia, and hypophosphatemia. All normalized after the recovery from pneumonia and the administration of spironolactone. The extracellular volume expansion associated with increased tubular Na reabsorption by the aldosterone-sensitive distal nephron and the resulting increase in CCr caused an inhibition of proximal tubular reabsorption of uric acid, Ca, and inorganic phosphate, leading to their renal loss and therefore hypouricemia, hypocalcemia, and hypophosphatemia, respectively. In this patient, the increased circulating cortisol associated with the stress of inflammation caused by pneumonia triggered the development of pseudoaldosteronism.


Burden of disease - prevalence and incidence of renal disease in India. Chronic Kidney Disease (CKD) burden is increasing worldwide. In developing countries like India, limited financial resources and lack of infrastructure put a severe strain on existing health policies in the light of the increasing burden of CKD. The exact prevalence of CKD in India is not known due to lack of adequate data recording systems both in the Government and insurance sectors. Recently with the support of the Indian society of Nephrology, a CKD registry has been formed with the hope of generating adequate information about CKD patients in India. Here we have reviewed various published studies on the magnitude of CKD in India. Three studies which have been carried out in different parts of India have been reviewed to examine the prevalence of CKD, which ranges from 0.79% to 1.4%. The incidence of End Stage Renal Disease was estimated to be 181 per million population in 2005 in central India. Many more such efforts are needed across our country in order to determine the exact burden of CKD.