Translation and validation of Cerebral Palsy Quality of Life Questionnaire-Teen in Hong Kong Chinese population [CP QoL-Teen (HK)].

Cerebral palsy (CP) is an early onset, non-progressive, neuromotor disorder. Adolescence is the transition from childhood to adulthood when changes in physical and emotional aspects and self-perception occur further imposing an impact to quality of life (QoL) in individuals with CP. Cerebral Palsy Quality of Life (CP QoL) Teen is a questionnaire examining different domains of QoL for adolescents with CP. This study is aimed at translating and validating self-report and proxy-report CP QoL-Teen (HK). Prior approval of translation has been obtained. Forward and backward translations were performed following standardized translation procedures. Participants and their caregivers were asked to complete self-report and proxy-report CP QoL-Teen (HK), and Child Health Questionnaire (CHQ). Internal consistency and test-retest reliability were assessed by Cronbach's alpha and intraclass correlation coefficient (ICC), respectively. Concurrent validity was evaluated by Spearman's rank correlation between subscales of CP QoL-Teen (HK) and CHQ as well as expanded and revised version of Gross Motor Function Classification System (GMFCS-E&R). Ninety-six participants completed the study. Of these, twenty participants completed CP QoL-Teen (HK) twice. Cronbach's α of CP QoL-Teen (HK) ranged from 0.84 to 0.95 suggesting excellent internal consistency. Moderate to excellent test-retest reliability were demonstrated in all subscales of CP QoL-Teen (HK) (self-report: ICC = 0.46-0.8; proxy-report: ICC = 0.40-0.72, p < 0.05). Weak to moderate association between subscales of CP QoL-Teen (HK) and CHQ (self-report: rs = 0.24-0.61; proxy-report: rs = - 0.41-0.60) was reported. CONCLUSION: This study showed that CP QoL-Teen (HK) has good psychometric properties. It is a valid and reliable tool to assess quality of life of adolescents with CP. WHAT IS KNOWN: • Cerebral Palsy Quality of life-Teen (CP QoL-Teen) is a validated tool with strong psychometric properties and clinical utility in gauging the QoL in adolescents with CP during their transition from childhood to adulthood when changes in physical and emotional aspects and self-perception occur. Yet, a locally validated tool is lacking in measuring the QoL for adolescents with CP in Hong Kong. WHAT IS NEW: • The Chinese translated version CP QoL-Teen (HK) is a valid and reliable tool to assess quality of life of adolescents with CP tailoring to the local cultural and social background with good psychometric properties being demonstrated.

Convection in a volatile nitrogen-ice-rich layer drives Pluto's geological vigour.

The vast, deep, volatile-ice-filled basin informally named Sputnik Planum is central to Pluto's vigorous geological activity. Composed of molecular nitrogen, methane, and carbon monoxide ices, but dominated by nitrogen ice, this layer is organized into cells or polygons, typically about 10 to 40 kilometres across, that resemble the surface manifestation of solid-state convection. Here we report, on the basis of available rheological measurements, that solid layers of nitrogen ice with a thickness in excess of about one kilometre should undergo convection for estimated present-day heat-flow conditions on Pluto. More importantly, we show numerically that convective overturn in a several-kilometre-thick layer of solid nitrogen can explain the great lateral width of the cells. The temperature dependence of nitrogen-ice viscosity implies that the ice layer convects in the so-called sluggish lid regime, a unique convective mode not previously definitively observed in the Solar System. Average surface horizontal velocities of a few centimetres a year imply surface transport or renewal times of about 500,000 years, well under the ten-million-year upper-limit crater retention age for Sputnik Planum. Similar convective surface renewal may also occur on other dwarf planets in the Kuiper belt, which may help to explain the high albedos shown by some of these bodies.

Reminiscing to teach others and prepare for death is associated with meaning in life through generative behavior in elderlies from four cultures.

Objectives: Reminiscence is considered an important aspect of successful ageing. Prominent reminiscence functions in old age are to pass on important experiences (Teach/Inform) and to prepare for death (Death Preparation). These reminiscence functions were hypothesized to be associated with generative behavior which in turn was hypothesized to be associated with meaning in life. Thus, we tested an indirect effect of reminiscence functions on meaning in life mediated by generative behavior.Method: Elderly participants provided information on reminiscence functions, generative behavior, and meaning in life. Participants were recruited in Cameroon, China (Hong Kong), the Czech Republic, and Germany, to test the generalizability of findings.Results: The assumed indirect effect was identified: Reminiscence functions were associated with meaning in life via generative behavior. This pattern was found for all cultural samples.Conclusion: Albeit results have to be interpreted with caution as they are based on cross-sectional data, findings suggest that these reminiscence functions motivate generative behavior and thus indirectly affect meaning in life in elderlies from all four cultural contexts. In future studies, this effect needs to be replicated with a broader age range and a more fine-grained measure of generative behavior to account for potential differences in culturally appropriate generative outlets.

Can we really diagnose diabetes during pregnancy?

OBJECTIVE: To identify the accuracy of diagnosing postpartum diabetes and glucose intolerance using antepartum glycosylated hemoglobin (HbA1c) and fasting glucose values. STUDY DESIGN: A retrospective Hawaiian cohort of women with gestational diabetes during 2004-2011 were evaluated. Antepartum HbA1c and postpartum 75-g glucose tolerance tests were obtained. RESULTS: An antepartum HbA1c value of ≥6.5% had a 45.7% sensitivity, a 96% specificity and a 40% positive predictive value (PPV) for predicting postpartum diabetes. An antepartum HbA1c value of ≥6.5% had a 6.6% sensitivity, a 94.2% specificity and a 27% PPV for predicting postpartum impaired glucose tolerance. An antepartum HbA1c value of ≥6.5% had a 10.3% sensitivity, a 95.7% specificity and a 33.3% PPV for predicting postpartum impaired fasting glucoses. CONCLUSION: We could not demonstrate a clinically useful PPV for diagnosing postpartum diabetes or glucose intolerance using an antepartum elevated HbA1c value of ≥6.5% or a fasting glucose level of ≥90 mg/dL.

Understanding the In Vitro-In Vivo Nexus: Advanced correlation models predict clinical performance of liposomal doxorubicin.

In the century of precision medicine and predictive modeling, addressing quality-related issues in the medical supply chain is critical, with 62 % of the disruptions being attributable to quality challenges. This study centers on the development and safety of liposomal doxorubicin, where animal studies alone often do not adequately explain the complex interplay between critical quality attributes and in vivo performances. Anchored in our aim to elucidate this in vitro-in vivo nexus, we compared TLD-1, a novel liposomal doxorubicin delivery system, against the established formulations Doxil® and Lipodox®. Robust in vitro-in vivo correlations (IVIVCs) with excellent coefficients of determination (R2 > 0.98) were obtained in the presence of serum under dynamic high-shear conditions. They provided the foundation for an advanced characterization and benchmarking strategy. Despite the smaller vesicle size and reduced core crystallinity of TLD-1, its release behavior closely resembled that of Doxil®. Nevertheless, subtle differences between the dosage forms observed in the in vitro setting were reflected in the bioavailabilities observed in vivo. Data from a Phase-I clinical trial facilitated the development of patient-specific IVIVCs using the physiologically-based nanocarrier biopharmaceutics model, enabling a more accurate estimation of doxorubicin exposure. This advancement could impact clinical practice by allowing for more precise dose estimation and aiding in the assessment of the interchangeability of generic liposomal doxorubicin.

[Factors influencing the quality of life of elderly living in a pre-fabricated housing complex in the Sichuan earthquake area].

BACKGROUND: The 2008 Sichuan Earthquake caused great damage to the environment and property. In the aftermath, many citizens were relocated to live in newly constructed prefabricated (prefab) communities. PURPOSE: This paper explored the current quality of life (QOL) of elderly residents living in prefabricated communities in areas damaged by the Sichuan earthquake and identified factors of influence on QOL values. The ultimate objective was to provide evidence-based guidance for heath improvement measures. METHODS: The authors used the short form WHOQOL-BREF to assess the quality of life of 191 elderly residents of prefabricated communities in the Sichuan Province 2008 earthquake zone. A Student's t-test, variance analysis, and stepwise multivariate regression methods were used to test the impact of various factors on QOL. RESULTS: Results indicate the self-assessed QOL of participants as good, although scores in the physical (average 56.2) and psychological (average 45.7) domains were significantly lower than the norm in China. Marital status, capital loss in the earthquake, number of children, level of perceived stress, income, interest, and family harmony each correlated with at least one of the short form WHOQOL-BREF domains in t-test and one-way analyses. After excluding for factor interaction effects using multivariate regression, we found interest, family harmony, monthly income and stress to be significant predictors of physical domain QOL, explaining 13.8% of total variance. Family harmony and interest explained 15.3% of total variance for psychological domain QOL; stress, marital status, family harmony, capital loss in the earthquake, number of children and interest explained 19.5% of total variance for social domain QOL; and stress, family harmony and interest explained 16.5% of total variance for environmental domain QOL. Family harmony and interest were significant factors across all domains, while others influenced a smaller proportion. CONCLUSIONS: Quality of life for elderly living in prefab communities should be improved. The authors hope study findings will increase awareness among healthcare providers regarding the quality of life of this vulnerable population. Study results suggest that key steps to promoting QOL in this population include improving family harmony, helping to cultivate well-rounded interests, alleviating economic stresses, providing necessary medical and psychological counseling services, and affording more social support.

Assessing Lung Parenchymal Enhancement on Dual-Energy CT Pulmonary Angiograms: Potential utility of dual-energy technique as an angiographic and parenchymal 'one-stop shop' in the initial workup of patients with pulmonary symptoms.

OBJECTIVE: The aim of this study was to assess the enhancement of lung parenchyma on dual-energy (DE) computed tomogram (CT) by comparing attenuation between routine post-contrast and dual-energy generated virtual unenhanced (VU) images. METHODS: Patients presenting to the Emergency Department who subsequently underwent DE-CT pulmonary angiogram from the 1st to the 30th of November were enrolled. The DE data set obtained was used to generate VU images. Attenuation in Hounsfield units (HU) was measured at two sites for each patient and compared between VU and routine post-contrast (PC) reconstructions. Statistical analysis was performed using paired-samples t-test. RESULTS: There is a statistical difference between lung parenchymal attenuation value between the CV and PC images, denser in the PC dataset and also towards the bases, with a mean HU of -841 and -817 (difference of 24) respectively. CONCLUSIONS: This study confirms increased lung parenchymal density when comparing PC and VU reconstructions. Based on results, the paper recommends utilising dual-energy capabilities for VU reconstructions in CTPAs to optimise assessment of lung parenchyma.

Investigation of the pharmacokinetics of romiplostim in rodents with a focus on the clearance mechanism.

PURPOSE: Romiplostim, a treatment for adults with immune thrombocytopenia (ITP), is a novel thrombopoietin mimetic agent with a similar mechanism of action as thrombopoietin with no sequence homology. Structurally, it is a peptibody containing thrombopoietin mimetic peptides and the Fc portion of human IgG(1). We investigated romiplostim pharmacokinetics in rodents with a focus on the clearance mechanism. METHODS: Studies with appropriate controls were conducted in four models: FcRn knockout mice, thrombocytopenic mice, splenectomized rats, and bilateral nephrectomized rats. Catabolic breakdown of romiplostim was investigated in normal rats. The primary analytical method determines the intact/active romiplostim concentration, and the secondary method determines the sum of romiplostim and its catabolic degradants. RESULTS: FcRn interaction results in prolonged exposure. Platelets are involved in the target-mediated elimination, a saturable process and more prominent at low dose. Splenectomy does not affect the romiplostim pharmacokinetics in rats, an observation not unexpected. Nephrectomy in rats results in a greater increase of romiplostim exposure at a higher romiplostim dose, a nonlinearity likely due to saturation of competing pathway. Catabolism plays a major role in romiplostim elimination. CONCLUSION: Romiplostim clearance involves multiple mechanisms, including a nonlinear pathway. Consequently, the relative contribution of different mechanisms appears to be dose dependent.

Development and pilot-testing of a Decision Aid for use among Chinese women facing breast cancer surgery.

BACKGROUND: Women choosing breast cancer surgery encounter treatment decision-making (TDM) difficulties, which can cause psychological distress. Decision Aids (DAs) may facilitate TDM, but there are no DAs designed for Chinese populations. We developed a DA for Chinese women newly diagnosed with breast cancer, for use during the initial surgical consultation. AIMS: Conduct a pilot study to assess the DA acceptability and utility among Chinese women diagnosed with breast cancer. METHODS: Women preferred the DA in booklet format. A booklet was developed and revised and evaluated in two consecutive pilot studies (P1 and P2). On concluding their initial diagnostic consultation, 95 and 38 Chinese women newly diagnosed with breast cancer received the draft and revised draft DA booklet, respectively. Four-day post-consultation, women had questionnaires read out to them and to which they responded assessing attitudes towards the DA and their understanding of treatment options. RESULTS: The original DA was read/partially read by 66/22% (n = 84) of women, whilst the revised version was read/partially read by 74/16% (n = 35), including subliterate women (χ(2) = 0.76, P = 0.679). Knowledge scores varied with the extent the booklet was read (P1: F = 12.68, d.f. 2, P < 0.001; P2: F = 3.744, d.f. 2, P = 0.034). The revised, shorter version was graphically rich and resulted in improved perceived utility, [except for the 'treatment options' (χ(2) = 5.50, P = 0.019) and 'TDM guidance' (χ(2) = 8.19, P = 0.004) sections] without increasing anxiety (F = 0.689, P = 0.408; F = 3.45, P = 0.073). CONCLUSION: The DA was perceived as acceptable and useful for most women. The DA effectiveness is currently being evaluated using a randomized controlled trial.

Development of Gross Motor Evaluation for Children Aged 18 to 42 Months.

PURPOSE: To test the reliability and validity of the gross motor items making up a new instrument, Hong Kong Comprehensive Assessment Scales for Toddlers (HKCAS-T) for quantifying gross motor development among children aged 18 to 42 months. METHODS: The 37 items were administered to 330 children, including 258 typically developing children and 72 children with gross motor delay. RESULTS: Rasch analyzes indicated that the fit statistics of the 37 items were within the acceptable range. The assessment was found able to differentiate between typically developing children and those with gross motor delay and among children of different ages. The raw score reliability (KR-20) was 0.94. CONCLUSION: The new instrument is a promising alternative for assessing young children's gross motor development.

Spatiotemporal dipole source localization of face processing ERPs in adolescents: a preliminary study.

BACKGROUND: Despite extensive investigation of the neural systems for face perception and emotion recognition in adults and young children in the past, the precise temporal activation of brain sources specific to the processing of emotional facial expressions in older children and adolescents is not well known. This preliminary study aims to trace the spatiotemporal dynamics of facial emotion processing during adolescence and provide a basis for future developmental studies and comparisons with patient populations that have social-emotional deficits such as autism. METHODS: We presented pictures showing happy, angry, fearful, or neutral facial expressions to healthy adolescents (aged 10-16 years) and recorded 128-channel event-related potentials (ERPs) while they performed an emotion discrimination task. ERP components were analyzed for effects of age and emotion on amplitude and latency. The underlying cortical sources of scalp ERP activity were modeled as multiple equivalent current dipoles using Brain Electrical Source Analysis (BESA). RESULTS: Initial global/holistic processing of faces (P1) took place in the visual association cortex (lingual gyrus) around 120 ms post-stimulus. Next, structural encoding of facial features (N170) occurred between 160-200 ms in the inferior temporal/fusiform region, and perhaps early emotion processing (Vertex Positive Potential or VPP) in the amygdala and orbitofrontal cortex. Finally, cognitive analysis of facial expressions (P2) in the prefrontal cortex and emotional reactions in somatosensory areas were observed from about 230 ms onwards. The temporal sequence of cortical source activation in response to facial emotion processing was occipital, prefrontal, fusiform, parietal for young adolescents and occipital, limbic, inferior temporal, and prefrontal for older adolescents. CONCLUSION: This is a first report of high-density ERP dipole source analysis in healthy adolescents which traces the sequence of neural activity within the first 500 ms of categorizing emotion from faces. Our spatio-temporal brain source models showed the presence of adult-like cortical networks for face processing in adolescents, whose functional specificity to different emotions appear to be not yet fully mature. Age-related differences in brain activation patterns illustrate the continued development and maturation of distinct neural systems for processing facial expressions during adolescence and possible changes in emotion perception, experience, and reaction with age.

Efficacy and safety of 20% albumin fluid loading in healthy subjects: a comparison of four resuscitation fluids.

Recently, buffered salt solutions and 20% albumin (small volume resuscitation) have been advocated as an alternative fluid for intravenous resuscitation. The relative comparative efficacy and potential adverse effects of these solutions have not been evaluated. In a randomized, double blind, cross-over study of six healthy male subjects we compared the pulmonary and hemodynamic effects of intravenous administration of 30 ml/kg of 0.9% saline, Hartmann's solution and 4% albumin, and 6 ml/kg of 20% albumin (albumin dose equivalent). Lung tests (spirometry, ultrasound, impulse oscillometry, diffusion capacity, and plethysmography), two- to three-dimensional Doppler echocardiography, carotid applanation tonometry, blood gases, serum/urine markers of endothelial, and kidney injury were measured before and after each fluid bolus. Data were analyzed with repeated measures ANOVA with effect of fluid type examined as an interaction. Crystalloids caused lung edema [increase in ultrasound B line (P = 0.006) and airway resistance (P = 0.009)], but evidence of lung injury [increased angiopoietin-2 (P = 0.019)] and glycocalyx injury [increased syndecan (P = 0.026)] was only observed with 0.9% saline. The colloids caused greater left atrial stretch, decrease in lung volumes, and increase in diffusion capacity than the crystalloids, but without pulmonary edema. Stroke work increased proportionally to increase in preload with all four fluids (R2 = 0.71). There was a greater increase in cardiac output and stroke volume after colloid administration, associated with a reduction in afterload. Hartmann's solution did not significantly alter ventricular performance. Markers of kidney injury were not affected by any of the fluids administrated. Bolus administration of 20% albumin is both effective and safe in healthy subjects. NEW & NOTEWORTHY Bolus administration of 20% albumin is both effective and safe in healthy subjects when compared with other commonly available crystalloids and colloidal solution.

Abnormal spatiotemporal processing of emotional facial expressions in childhood autism: dipole source analysis of event-related potentials.

Previous studies of face processing in autism suggest abnormalities in anatomical development, functioning and connectivity/coordination of distributed brain systems involved in social cognition, but the spatial sequence and time course of rapid (sub-second) neural responses to emotional facial expressions have not been examined in detail. Source analysis of high-density event-related potentials (ERPs) is an optimal means to examine both the precise temporal profile and spatial location of early electrical brain activity in response to emotionally salient stimuli. Therefore, we recorded 128-channel ERPs from high-functioning males with autism (aged 6-10 years), and age-, sex- and IQ-matched typically developing controls during explicit and implicit processing of emotion from pictures showing happy, angry, fearful, sad and neutral facial expressions. Children with autism showed normal patterns of behavioural and ERP (P1, N170 and P2) responses. However, dipole source analysis revealed that ERP responses relating to face detection (visual cortex) and configural processing of faces (fusiform gyrus), as well as mental state decoding (medial prefrontal lobe), were significantly weaker and/or slower in autism compared with controls during both explicit and implicit emotion-processing tasks. Slower- and larger-amplitude ERP source activity in the parietal somatosensory cortices possibly reflected more effortful compensatory analytical strategies used by the autism group to process facial gender and emotion. Such aberrant neurophysiological processing of facial emotion observed in children with autism within the first 300 ms of stimulus presentation suggests abnormal cortical specialization within social brain networks, which would likely disrupt the development of normal social-cognitive skills.

Hong Kong study using valsartan in IgA nephropathy (HKVIN): a double-blind, randomized, placebo-controlled study.

BACKGROUND: Previous studies showed that angiotensin-receptor blocker (ARB) therapy decreased proteinuria and possibly slowed the rate of renal function decline in patients with chronic proteinuric nephropathies. We performed a double-blind, randomized, placebo-controlled, multicenter study on the ARB valsartan in the treatment of patients with immunoglobulin A (IgA) nephropathy. METHODS: From 6 centers, we recruited 109 patients with IgA nephropathy who had either: (1) proteinuria with protein greater than 1 g/d and serum creatinine level less than 2.8 mg/dL (< 250 micromol/L), or (2) serum creatinine level of 1.4 to 2.8 mg/dL (120 to 250 micromol/L) regardless of degree of proteinuria. Patients were randomly assigned to administration of either valsartan, 80 mg/d (titrated up to 160 mg/d for blood pressure control), or placebo for 104 weeks. Additional antihypertensive therapy was allowed to achieve a target blood pressure of 140/90 mm Hg. The primary end point was doubling of serum creatinine level or dialysis-dependent renal failure. Secondary outcomes included change in proteinuria and decrease in glomerular filtration rate (GFR). RESULTS: There were 54 patients in the treatment group and 55 patients in the placebo group. Baseline clinical characteristics were similar between groups, although the treatment group had a marginally greater baseline GFR (87 +/- 36 versus 78 +/- 38 mL/min/1.73 m2 [1.45 +/- 0.60 versus 1.30 +/- 0.63 mL/s/1.73 m2];P = 0.29) and less proteinuria (protein, 1.8 +/- 1.2 versus 2.3 +/- 1.7 g/d; P = 0.21) than the placebo group. Average blood pressures during the study were 92.7 +/- 10.6 mm Hg in the treatment group and 100.9 +/- 9.1 mm Hg in the placebo group (P < 0.001). During the study period, 4 patients in the placebo group and 1 patient in the treatment group reached the primary end point (log-rank test, P = 0.18). Proteinuria decreased significantly in the treatment group (protein, 1.8 +/- 1.2 to 1.2 +/- 1.2 g/d; P = 0.03), but did not change in the placebo group. With multiple linear regression models, valsartan treatment resulted in a 33.0% decrease in proteinuria (95% confidence interval, 10.9 to 55.1) after adjusting for other confounding factors. There was a significant decrease in mean rate of GFR decrease in the valsartan-treated group (-5.62 +/- 6.79 mL/min/y [-0.09 +/- 0.11 mL/s/y]) compared with the placebo group (-6.98 +/- 6.17 mL/min/y [-0.12 +/- 0.10 mL/s/y]) throughout the study period after adjustment for average blood pressure and proteinuria (P = 0.014). CONCLUSION: Valsartan significantly decreases proteinuria and slows renal deterioration in patients with IgA nephropathy after adjustment for confounding factors, notably blood pressure. The long-term benefit of valsartan needs to be confirmed with additional studies.

Generativity does not necessarily satisfy all your needs: Associations among cultural demand for generativity, generative concern, generative action, and need satisfaction in the elderly in four cultures.

The present study examines the association between various facets of generativity, that is, cultural demand for generativity, generative concern, and generative action, with the satisfaction of the needs for relatedness, competence, and autonomy in samples of elderly from Cameroon, China (Hong Kong), the Czech Republic, and Germany. Participants provided information on self-transcendence values (internalized cultural demand), generative concern and action, and need satisfaction. Results suggest, first, that internalized cultural demand affects generative action indirectly through generative concern, second, that generative concern has a positive direct effect on need satisfaction, but that, third, there is also an indirect effect of generative concern on need satisfaction through generative action, which, fourth, is positive for the needs for relatedness and competence but negative for the need for autonomy. These findings were culture-invariant in our study, suggesting generalizability to other cultures. They are discussed with respect to the role of values in generativity and a possible trade-off of generative action for the satisfaction of needs at least in the elderly.

Rosiglitazone reduces insulin requirement and C-reactive protein levels in type 2 diabetic patients receiving peritoneal dialysis.

BACKGROUND: Glycemic control is important in determining the outcome of patients with diabetes on dialysis therapy. However, the choice of oral hypoglycemia agent is limited in these patients. Very often, a high dose of insulin is required because of the uremia-associated insulin-resistant state. Rosiglitazone (RSG), a thiazolidinedione, can improve insulin resistance, and its excretion does not rely on renal function. Moreover, it has an anti-inflammatory effect that might be beneficial in patients with renal failure. METHODS: An open-label randomized study was performed in which 52 patients with type 2 diabetes on peritoneal dialysis therapy administered a constant dosage of subcutaneous insulin with stable glycemic control were randomly assigned to the administration of either RSG (fixed dose, 4 mg) plus insulin or insulin alone. Insulin was titrated to maintain hemoglobin A1c (HbA1c) and blood glucose at pretreatment levels. Study duration was 24 weeks. RESULTS: Both groups had similar baseline demographic characteristics, HbA1c and glucose levels, insulin requirement, and C-reactive protein (CRP) levels. Insulin requirement was decreased significantly in the RSG group (27.88 +/- 17.6 to 22.4 +/- 15.21 U/d; P < 0.001). There was a significantly greater decrease in insulin dosage in the RSG than control group (-21.5% versus +0.5%; P = 0.03), whereas glycemic control was similar between groups. At the end of the study, the RSG group also had significantly lower CRP levels than the control group (2.21 versus 8.59 mg/L; P = 0.03). No significant increase in such adverse effects as hypoglycemia, liver impairment, and fluid overload was observed in the RSG group. However, the RSG group was associated with more weight gain. Multivariate regression analysis (using decrease in HbA1c and lipid levels, change in insulin dosage, and treatment with RSG, with lipid-lowering agents) showed that only treatment with RSG was an independent predictor for posttreatment CRP level (P = 0.016). CONCLUSION: RSG in combination with insulin is well tolerated and beneficial in the treatment of patients with type 2 diabetes on peritoneal dialysis therapy by improving insulin sensitivity and decreasing inflammatory response.

Genetics of common progressive renal disease.

Familial aggregation of common chronic kidney diseases provides a unique opportunity to investigate the susceptibility genetic and environmental factors. In the past decade, a wealth of new data has become available concerning the genetic susceptibility leading to numerous nephropathies. Knowledge of the genetic components allows better understanding of initiation and progression of these chronic kidney diseases. In addition, one can envision that identification of genetically susceptible individuals might lead to earlier diagnosis and potential reversal of the current epidemic of end-stage renal disease. The goal of the current discussion is to review various issues pertaining to the role of genetic factors in common chronic kidney diseases, as exemplified by two leading causes of end-stage renal diseases worldwide, nephropathy of type 2 diabetes and IgA nephropathy. The genetic and environmental interplay leading to the nephropathies is highlighted.

Differential effects of transforming growth factor-beta on the synthesis of connective tissue growth factor and vascular endothelial growth factor by peritoneal mesothelial cell.

BACKGROUND: Previous studies found that transforming growth factor-beta (TGF-beta) plays a conflicting role in peritoneal fibrosis. We hypothesise that TGF-beta acts on peritoneal mesothelial cells (PMC) via VEGF and CTGF as downstream mediators. METHODS: The effect of TGF-beta in primary culture of rat PMC was studied. VEGF and CTGF mRNA expression was examined by real time quantitative polymerase chain reaction (RT-QPCR), and VEGF antigen level in cell supernatant by ELISA. RESULTS: Incubation of rat PMC with TGF-beta resulted in a time- (3-72 h) and concentration- (0-50 pg/ml) dependent increase in VEGF mRNA expression, and VEGF protein level in the cell supernatant. When stimulated with TGF-beta 100 pg/ml, there was a 20-fold up-regulation of VEGF mRNA expression (p < 0.001). The CTGF mRNA expression and protein level of PMC was slightly increased at low concentration of TGF-beta (50 pg/ml) but decreased at a higher concentration (100 pg/ml or above). The effect of TGF-beta on PMC CTGF, but not VEGF, gene expression was inhibited by Smad decoy oligodeoxynucleotide. The effect of TGF-beta on PMC VEGF gene expression and protein synthesis was inhibited by PD98059 (a specific MAP kinase inhibitor) and chelerythrine (a specific protein kinase C inhibitor), but not cholera toxin (activator of cyclic AMP) or herbimycin A (inhibitor of protein tyrosine kinase). The up-regulation of CTGF mRNA expression was inhibited by PD98059, but not chelerythrine, cholera toxin or herbimycin A. Furthermore, CTGF gene expression in TGF-beta-stimulated PMC was inhibited by co-administration of recombinant VEGF. CONCLUSIONS: Our data demonstrate that TGF-beta induces PMC production of VEGF and CTGF via different signalling pathways. At high concentration of TGF-beta, VEGF production predominates and CTGF production was inhibited. Since CTGF and VEGF have different biologic effects, our results may explain the complex activity of TGF-beta in peritoneal physiology.

Effects of an angiotensin-converting enzyme inhibitor on residual renal function in patients receiving peritoneal dialysis. A randomized, controlled study.

BACKGROUND: Residual renal function is an important determinant of mortality and morbidity in patients receiving peritoneal dialysis. However, few studies have evaluated therapeutic approaches for preserving residual renal function after the initiation of dialysis. OBJECTIVE: To test the hypothesis that the angiotensin-converting enzyme (ACE) inhibitor ramipril slows the decline in residual renal function in patients with end-stage renal failure treated with peritoneal dialysis. DESIGN: Randomized, open-label, controlled trial. SETTING: Single-center study in the dialysis unit of a university teaching hospital. PATIENTS: 60 patients receiving peritoneal dialysis. MEASUREMENTS: Patients were randomly assigned to ramipril (5 mg daily) or no treatment. The target blood pressure was 135/85 mm Hg or less. Rate of decline in residual glomerular filtration rate (GFR) and development of complete anuria were compared among groups. RESULTS: Over 12 months, average residual GFR declined by 2.07 mL/min per 1.73 m2 in the ramipril group versus 3.00 mL/min per 1.73 m2 in the control group (P = 0.03). The difference between the average changes in residual GFR in the ramipril and control groups from baseline to 12 months was 0.93 mL/min per 1.73 m2 (95% CI, 0.09 to 1.78 mL/min per 1.73 m2). At 12 months, 14 patients in the ramipril group and 22 in the control group developed anuria. With intention-to-treat multivariable analysis using the Cox model, it was estimated that at 3, 6, and 9 months, patients assigned to ramipril had a higher adjusted hazard of complete anuria than did patients assigned to no treatment. Of the 25 patients who still did not have complete anuria at 12 months, those assigned to ramipril had a better prognosis than did those assigned to no treatment (adjusted hazard ratio, 0.58 [CI, 0.36 to 0.94]). The rates of death from any cause, duration of hospitalization, and cardiovascular events did not differ significantly between groups. CONCLUSIONS: Although the trial was small and had a limited ability to exclude effects of potential confounding factors, the angiotensin-converting enzyme inhibitor ramipril may reduce the rate of decline of residual renal function in patients with end-stage renal failure treated with peritoneal dialysis.