Effect of cerivastatin on proteinuria and urinary podocytes in patients with chronic glomerulonephritis.

BACKGROUND: We previously reported urinary podocytes to be a marker of glomerular injury. The aim of the present study was to determine whether cerivastatin, a newly developed, potent synthetic statin, affects proteinuria and urinary podocyte excretion in patients with chronic glomerulonephritis (CGN). METHODS: We randomly assigned 40 normotensive hypercholesterolemic patients with CGN to receive either cerivastatin 0.15 mg/day (n=20) or placebo (n=20). Subjects comprised 24 men and 16 women, with a mean age of 40.8+/-14.4 years; 27 had IgA nephropathy and 13 had non-IgA proliferative glomerulonephritis. Treatment was continued for 6 months. Plasma total cholesterol, HDL-cholesterol, LDL-cholesterol and triglycerides, urinary protein excretion and the number of podocytes were measured before treatment and at 3 and 6 months after treatment. RESULTS: After 6 months, a significant reduction in total cholesterol (P<0.001), LDL-cholesterol (P<0.001) and triglycerides (P<0.05), and a significant increase in HDL-cholesterol (P<0.001) were observed in the group treated with cerivastatin. Urinary protein excretion decreased from 1.8+/-0.6 to 0.8+/-0.4 g/day, (P<0.01) in this group, and urinary podocyte excretion decreased from 1.6+/-0.6 to 0.9+/-0.4 cells/ml (P<0.01). However, placebo showed little effect on these lipid levels, urinary protein excretion and urinary podocyte excretion. The differences between the cerivastatin group and the placebo group were significant (cholesterol, P<0.001; LDL-cholesterol, P<0.001; triglycerides, P<0.05; HDL-cholesterol, P<0.001; urinary protein, P<0.01; and urinary podocytes, P<0.01). CONCLUSION: Statins such as cerivastatin may be beneficial for restoration of injured podocytes in patients with CGN and hypercholesterolaemia.     

Propofol Increases Pulmonary Artery Smooth Muscle Myofilament Calcium Sensitivity: Role of Protein Kinase C

Background: Vascular smooth muscle tone is regulated by changes in intracellular free Ca2+ concentration ([Ca2+]i) and myofilament Ca2+ sensitivity. These cellular mechanisms could serve as targets for anesthetic agents that alter vasomotor tone. This study tested the hypothesis that propofol increases myofilament Ca2+ sensitivity in pulmonary artery smooth muscle (PASM) via the protein kinase C (PKC) signaling pathway.

Methods: Canine PASM strips were denuded of endothelium, loaded with fura-2/AM, and suspended in modified Krebs- Ringer's buffer at 37[degrees]C for simultaneous measurement of isometric tension and [Ca2+]i.

Results: The KCl (30 mm) induced monotonic increases in [Ca2+]i and tension. Verapamil, an L-type Ca2+ channel blocker, attenuated KCl-induced increases in [Ca2+]i and tension to an equal extent. In contrast, propofol attenuated KCl-induced increases in [Ca2+]i to a greater extent than concomitant changes in tension and caused an upward shift in the peak tension-[Ca2+]i relation. Increasing extracellular Ca2+ in the presence of 30 mm KCl resulted in similar increases in [Ca2+]i in control and propofol-pretreated strips, whereas concomitant increases in tension were greater during propofol administration. The Ca2+ ionophore, ionomycin (0.1 [mu]m), increased [Ca2+]i to approximately 50% of the value induced by 60 mm KCl. Under these conditions, propofol (10, 100 [mu]m) caused increases in tension equivalent to 11 +/- 2 and 28 +/- 3% of the increases in tension in response to 60 mm KCl, whereas [Ca2+]i was slightly decreased. Similar effects were observed in response to the PKC activator, phorbol 12-myristate 13-acetate (PMA, 1 [mu]m). Specific inhibition of PKC with bisindolylmaleimide I before ionomycin administration decreased the propofol- and PMA-induced increases in tension and abolished the propofol- and PMA-induced decreases in [Ca2+]i. Selective inhibition of Ca2+-dependent PKC isoforms with Go 6976 also attenuated propofol-induced increases in tension.     

Determinants of mortality in patients with severe blunt head injury

CONTEXT: Head injury is the leading cause of traumatic death in the United States. HYPOTHESIS: A set of clinical parameters available soon after injury can be used to accurately predict outcome in patients with severe blunt head trauma. DESIGN: Validation cohort study. SETTING: Urban level I trauma center. PATIENTS AND METHODS: Data from patients with severe blunt head injury, as defined by inability to follow commands, were prospectively entered into a neurosurgical database and analyzed. The impact on survival of 23 potentially predictive parameters was studied using univariate analysis. Logistic regression models were used to control for confounding factors and to assess interactions between variables, whose significance was determined by univariate analysis. Goodness of fit was calculated with the Hosmer-Lemeshow c statistic. The predictability of the logistic model was evaluated by measuring the area under the receiver operating characteristic curve (AUC). RESULTS: Logistic regression analysis revealed that 5 risk factors were independently associated with death. These variables included systemic hypotension in the emergency department, midline shift on computed tomographic scan, intracranial hypertension, and absence of pupillary light reflex. A low Glasgow Coma Scale score and advanced age were found to be highly correlated risk factors that, when combined, were independently associated with mortality. The model showed acceptable goodness of fit, and the AUC was 80.5%. CONCLUSIONS: Systemic hypotension and intracranial hypertension are the only independent risk factors for mortality that can be readily treated during the initial management of patients with severe head injuries. When used together, Glasgow Coma Scale score and age are significant predictors of mortality.     

Lack of association between adolescent idiopathic scoliosis and previously reported single nucleotide polymorphisms in MATN1, MTNR1B,TPH1, and IGF1 in a Japanese population

Adolescent idiopathic scoliosis (AIS) is a spinal deformity most commonly arising in apparently healthy girls around puberty. AIS has a strong genetic predisposition. Several genetic associations between AIS and single nucleotide polymorphisms (SNPs) have been reported; common SNPs in the genes for matrilin 1 (MATN1), melatonin receptor 1B (MTNR1B), tryptophan hydroxylase 1 (TPH1), and insulin‐like growth factor 1 (IGF1) are reported to be associated with AIS in Chinese. However, these associations have not been replicated so far. To confirm the associations, we compared these SNPs with AIS predisposition and curve severity in a population of Japanese females consisting of 798 AIS patients and 1,239 controls. All the subjects were genotyped using the PCR‐based Invader assay. We found no association of any of the SNPs with AIS predisposition or curve severity. Considering the statistical power and sample size of the present study, we concluded that these SNPs are not associated with either AIS predisposition or curve severity in Japanese. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 29: 1055–1058, 2011     

Long-term culture of Japanese human embryonic stem cells in feeder-free conditions

Human pluripotent embryonic stem cells (hESCs) have great promise for research into human developmental biology, development of cell therapies for the treatment of diseases, toxicology, and drug discovery. Traditionally, undifferentiated hESCs are maintained on mouse embryonic fibroblasts (MEFs), which impede the clinical applications of hESCs. Here we have examined the long-term stability of the Japanese hESC line (KhES-1) in feeder-free culture. KhES-1 cells were cultured with MEF conditioned medium (CM) and different doses of basic fibroblast growth factor (bFGF) in six-well-plates of which the surface was coated with Matrigel. KhES-1 cells were maintained for at least 40 passages. In this culture system, the cells maintained stable proliferation rates and steadily expressed Oct-4, Nanog, and alkaline phosphatase. In addition, KhES-1 cells maintained without direct feeder contact formed embryonic bodies with expression of markers from the three germ layers. Here we demonstrated that Japanese human embryonic stem cells KhES-1 were cultured long term in a feeder-free method, while retaining pluripotency in vitro.     

Preoperative proximal splenic artery embolization: a safe and efficacious portal decompression technique that improves the outcome of live donor liver transplantation

Terminal liver cirrhosis is associated with marked severe portal hypertension, which increases the risk of intraoperative hemorrhage and graft hyper-perfusion, especially, in small-for-size graft. In cases with developed collateral vessels, we often face difficulties in perihepatic dissection with blood stanching against bleeding during recipient hepatectomy. For aseptic preoperative portal decompression, we established the proximal splenic artery embolization (PSAE) technique. Sixty adult living donor liver transplantation recipients with viral/alcoholic hepatic failure were divided into two groups; PSAE group (n = 30) and non-PSAE (n = 30). In the PSAE group, the splenic artery was embolized proximal to the splenic hilum 12-18 h before surgery. PSAE enabled shortening of operating time, reduced blood loss, led to less need for transfusion, and significantly reduced the post-transplant portal venous velocity and ascites. PSAE was not associated with complications, e.g., splenic infarction, abscess, or portal thrombosis. Six of the non-PSAE patients required additional surgical intervention to resolve postoperative hemorrhage and three patients required secondary PSAE for arterial-steal-syndrome. The hospital mortality rate of PSAE patients (3.3%) was significantly better than that of the PSAE group (13.3%, P < 0.05). Preoperative noninvasive PSAE makes more efficient use of portal decompression; thus, it can potentially contribute to improvement of outcome.     

Predictive model for estimating risk of crush syndrome: a data mining approach

BACKGROUND: There is no standard triage method for earthquake victims with crush injuries because of a scarcity of epidemiologic and quantitative data. We conducted a retrospective cohort study to develop predictive models based on clinical data for crush injury in the Kobe earthquake. METHODS: The medical records of 372 patients with crush injuries from the Kobe earthquake were retrospectively analyzed. Twenty-one risk factors were assessed with logistic regression analysis for three outcomes relating to crush syndrome. Two types of predictive triage models--initial evaluation in the field and secondary assessment at the hospital--were developed using logistic regression analysis. Classification accuracy, Brier score and area under the receiver operating characteristic curve (AUC) were used to evaluate the model. RESULTS: The initial triage model, which includes pulse rate, delayed rescue, and abnormal urine color, has an AUC of 0.73. The secondary model, which includes WBC, tachycardia, abnormal urine color, and hyperkalemia, shows an AUC of 0.76. CONCLUSIONS: These triage models may be especially useful to nondisaster experts for distinguishing earthquake victims at high risk of severe crush syndrome from those at lower risk. Application of the model may allow relief workers to better utilize limited medical and transportation resources in the aftermath of a disaster.     

Low-Volume Walking Program Improves Cardiovascular-Related Health in Older Adults

Although numerous sources of evidence show that regular physical activity is beneficial to health, most individuals do not engage in a sufficient amount of physical activity to meet the guidelines set out by expert panels. In addition, the minimum amount of physical activity associated with reduced cardiovascular disease risk markers is not clear in older adults. The purpose of this study was to determine the effects of a 12-week walking program involving an exercise volume below the current minimum physical activity recommendation on cardiovascular disease risk markers in older adults. The participants were recruited from the following two groups separately: a walking group (n = 14) and a control group (n = 14). In the walking group, participants walked 30 to 60 minutes per session on 2 days per week for 12 weeks (average walking time, 49.4 ± 8.8 min/session). Plasma oxidised low-density lipoprotein concentrations tended to be lower than baseline values in the walking group after 12 weeks (paired t-test, p = 0.127). The ratio of oxidised low-density lipoprotein to high-density lipoprotein cholesterol was significantly lower than the baseline ratio in the walking group after 12 weeks (paired t-test, p = 0.035). Resting systolic blood pressure and diastolic blood pressure were significantly lower than baseline values in the walking group after 12 weeks (paired t-tests, p = 0.002, p < 0.0005, respectively). Our findings demonstrate that a 12-week walking program comprising a low volume of physical activity confers a benefit to cardiovascular-related health in older adults.

Key Points

• It is important to consider baseline physical activity levels when evaluating physical activity program.
• Being physically active is important to reduce the potential risk marker of cardiovascular disease in older adults.
• These data imply that a small volume of 12-week walking program confers a benefit to cardiovascular-related health in older adults.

Key words: blood pressure, exercise, lipid metabolism, older adults, oxidised low-density lipoprotein     

Prediction of morbidity after lung resection with risk factors using treadmill exercise test.

OBJECTIVE: To predict accurate morbidity after lung resection using treadmill exercise test. METHODS: A total of 130 patients (108 men and 22 women, with mean age 67.1+/-11.4 years (range, 34-78 years)) of 1129 patients underwent standard lobectomy were performed both treadmill exercise test and spirometry preoperatively. We measured maximum oxygen uptake/body weight (VO2max/BW) and change in arterial blood oxygen pressure from rest to symptom-limited maximum loading (delta aPaO2) and calculated exercise-induced hypoxemia (delta PaO2/delta VO2/BW), and retrospectively compared these parameters for patients with and without complications. RESULTS: There were five patients with severe postoperative complications, including three requiring use of a respirator, two with home oxygen therapy. %Vital capacity, VC (%, 80.2+/-13.2 vs. 92.5+/-20.9, P=0.026), delta PaO2 (Torr, -29.3+/-4.3 vs. -13.2+/-10.8, P=0.0004), VO2max/BW (ml/min/kg, 16.5+/-2.9 vs. 20.6+/-5.1, P=0.018) and delta PaO2/delta VO2/BW (Torr/ml/min/kg, -1.98+/-0.26 vs. -0.57+/-0.47) were significantly associated with worse outcome. All the five patients with complications had delta PaO2/delta VO2/BW<-1.7. CONCLUSIONS: Treadmill exercise testing is a good method for assessment of cardiopulmonary reserve. Limited resection must be performed if delta PaO2/delta VO2/BW is under -1.7.