25462829
Blood Pressure Recordings within and outside the Clinic and Cardiovascular Events in Chronic Kidney Disease
Background: Blood pressure (BP) measured outside the clinic correlates better with cardiovascular outcomes in patients with essential hypertension. To assess the role of out-of-clinic BP recordings in predicting cardiovascular events in patients with chronic kidney disease (CKD), a prospective cohort study was conducted in 217 veterans with CKD. Methods: BP was measured outside the clinic at home and by 24-hour ambulatory recordings, and in the clinic by ‘routine’ and standardized methods. Patients were followed over a median of 3.4 years to assess the combined end-point of total mortality, myocardial infarction or stroke. Results: Average (±SD) home BP was 147.0 ± 21.4/78.3 ± 11.6 mm Hg, 24-hour ambulatory BP 133.5 ± 16.6/73.1 ± 11.1 mm Hg and in-clinic BPs were 155.2 ± 25.6/84.7 ± 14.2 mm Hg by the standardized method, and 144.5 ± 24.2/75.4 ± 14.7 mm Hg by the ‘routine’ method. A 1 SD increase in systolic BP increased the hazard ratio (HR) of the composite end-point by 1.16 (95% CI 0.89–1.50) for routine BP, 1.57 (95% CI 1.19–2.09) for standardized BP, 1.66 (95% CI 1.27–2.17) for home BP, and 1.42 (95% CI 1.10–1.84) for 24-hour ambulatory BP recording. The HR of the composite end-point was only significant for hypertension defined by 24-hour ambulatory BP monitoring (HR 2.22 (95% CI 1.23–4.01)). Adjusted for the propensity scores, BP measured by the ambulatory technique was not an independent predictor of cardiovascular events. Non-dipping was associated with increased cardiovascular risk, but not when adjusted for other risk factors. Conclusion: Risk factors that differentiate hypertension or non-dipping appear to confer a cardiovascular risk in CKD.
22176722
Alar web in cleft lip nose deformity: study in adult unilateral clefts.
BACKGROUND
The correction of alar webbing in unilateral cleft lip nose deformity is challenging because of progressive distortions in the alar web region during the period of growth. Alar webbing is a persistent universal deformity in both the primary and secondary cleft lip noses. The purpose of this article is to study the alar web deformity in adult patients with unilateral cleft lip noses.


METHODS
Twenty-five patients aged 13 years and older presenting with unilateral cleft nasal deformity were included. Preoperative and postoperative measurements of the nose, along with detailed intraoperative recording of the deformed anatomy, were done. Preoperative magnetic resonance imaging was also done in selected cases. Transcolumellar open rhinoplasty was performed in all the cases, and nasal septal straightening with centralization was done. Cleft alar base augmentation was done using bone graft to restore symmetry of the nasal tripod. Both the cleft and noncleft alar cartilages were extensively mobilized from the skin and mucosal sides. The overgrown and caudally slumped cleft-side alar cartilage was resected caudally and was then resuspended in a symmetrical position with the noncleft alar cartilage. A midline-strut septal cartilage extension graft was used to restore the tip aesthetics. The skin overlying the alar web was in-rolled after semilunar cartilage resection, and skin excision was also done to restore symmetry with the opposite vestibule. The remaining secondary cleft nasal and lip deformities were corrected depending upon the specific presenting pathologic abnormality.


RESULTS
The cleft alar cartilage was found to be caudally displaced in all the cases. The caudal border of the lateral crus was prolapsing in the cavity of the vestibule on the superomedial aspect and was tenting the skin in the area of the weak triangle, producing the characteristic alar web deformity. In the study group, the maximum width of the cleft alar cartilage at the level of the lateral crus was increased by approximately 4 mm when compared with the noncleft alar cartilage. The before- and after-rhinoplasty surgery results were objectively assessed using a patient, surgeon, and independent observer survey. The cosmetic result of the nasal tip complex was found to be very good and good (90%), satisfactory (5%), and poor (5%) in patients.


CONCLUSIONS
The alar web in unilateral cleft lip nose deformity is the result of caudal overgrowth and migration of the alar cartilage. The caudal edge of the prolapsed lateral crus overhangs the cleft-side nasal aperture on its superomedial aspect, producing this deformity. Satisfactory correction of this deformity should envisage caudal resection and repositioning of the dislocated alar cartilage along with caudal resection of the lateral crus with in-rolling of the skin after resection to achieve symmetric results in unilateral cleft lip rhinoplasty.
11453581
Proinflammatory effects of oxidative stress in chronic kidney disease: role of additional angiotensin II blockade.
Oxidative stress plays an important role in causing progressive chronic kidney disease (CKD). We examined the influence of add-on ANG II receptor blockade administered as losartan (50 mg/day for 1 mo) on oxidative stress and proinflammatory state of the kidney in patients with CKD. All subjects were taking an angiotensin-converting enzyme inhibitor plus other antihypertensive agents. Oxidative stress to lipids and proteins was measured by an HPLC assay for malondialdehyde (MDA) and carbonyl concentration, respectively. Urinary inflammation was measured by monocyte chemotactic protein-1 (MCP-1) excretion rate. The etiology of CKD was type 2 diabetes mellitus in 12 and glomerulonephritis in 4 patients. There was no change in proteinuria or 24-h ambulatory blood pressure (BP) with add-on ANG II receptor blockade with losartan therapy. Before losartan therapy, urinary protein and albumin oxidation were 99 and 71% higher, respectively, compared with in plasma (P < 0.05). There was a 35% reduction in urinary oxidized albumin with add-on losartan therapy (P = 0.036). Urinary and plasma MDA were elevated compared with age-matched controls. Urinary MDA was significantly reduced from 4.75 +/- 3.23 to 3.39 +/- 2.17 micromol/g creatinine with add-on losartan therapy. However, plasma MDA or oxidized proteins did not change in response to additional ANG II blockade. A good correlation was seen between the change in urinary oxidized albumin and MCP-1 levels (r = 0.61, P = 0.012). These data demonstrate that oxidative damage to urinary protein and lipids can be reduced with additional ANG II receptor blockade, independently of reductions in proteinuria or BP. Urinary measurements of markers of oxidative damage to lipids and proteins appear to be more sensitive than plasma measurements in patients with CKD. The significant association of the change in urinary MCP-1 with a reduction in oxidative stress supports the role of the redox state in the kidney with renal fibrosis and progressive kidney damage.
191311
Assessment of iothalamate plasma clearance: duration of study affects quality of GFR.
BACKGROUND AND OBJECTIVES
Measurement of GFR is important for the management of chronic kidney disease (CKD). Although bolus administration of radiocontrast agents is commonly used to measure GFR, the optimal duration of sampling to assess their plasma clearance is unknown. The purpose of this study was to evaluate whether the duration of plasma sampling influences precision and estimation of GFR.


DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS
GFR was measured by sampling plasma 12 times over 5 h in 56 patients with CKD (mean age 64 yr, 98% men, 79% Caucasian, 34% diabetics, estimated GFR 31.8 +/- 14.2 ml/min/1.73 m(2)). In a subset of 12 patients we measured GFR by sampling plasma 17 times over 10 h.


RESULTS
Short sampling intervals considerably overestimated GFR measured using total plasma iothalamate clearance, especially in larger patients. In the higher estimated GFR group (>30 ml/min/1.73 m(2)), the 5-h GFR was 17% higher and 2-h GFR 54% higher compared with the 10-h GFR, which averaged 40.3 ml/min/1.73 m(2). In the lower estimated GFR group (<30 ml/min/1.73 m(2)), the 5-h GFR was 36% higher and 2-h GFR 126% higher compared with the 10-h GFR, which averaged 22.2 ml/min/1.73 m(2). Short sampling duration also reduced the precision of the estimated GFR from 1.67% for 10-h GFR, to 3.48% for 5-h GFR, and to 7.07% for 2-h GFR.


CONCLUSIONS
GFR measured over a longer duration with multiple plasma samples spanning the distribution and elimination phases may improve precision and provide a better measure of renal function.
36005104
Volume Overload in Dialysis: The Elephant in the Room, No One Can See
interests of the authors. However, considering the totality of the evidence, I am less convinced that this marker is superior to other volume markers. First, there are few head-to-head studies comparing BIA to other established markers of volume. Second, there is no range that defines ‘normal’. Unlike blood pressure (BP) or cholesterol, there is no target that has been established. The normal values are obtained from healthy subjects whose body composition differs substantially from those on dialysis. Extrapolating from healthy subjects to those with ESRD on hemodialysis does not appear scientifically valid. Third, there is no study to my knowledge that demonstrates convincingly that compared to probing dry weight without BIA, BIA-guided dry weight reduction results in improved outcomes. Most data provided to support the use of BIA are associative and observational. A large amount of observational data does not prove causation. We therefore have to be cautious in interpreting these data as ‘strongly indicative of fluid overload’. Nearly all markers of volemia suffer from the same shortcomings. These shortcomings include lack of normative data, and data being largely observational and associative in nature. As an example, several observational studies suggest that B-type natriuretic peptide (BNP), NT-proBNP or other natriuretic peptides are associated with volume state among people with ESRD on dialysis [2–10] . However, only one study has been reported to date that relates the change in BNP to an intervention of probing dry weight [11] . In this study, a direct relationship existed at baseline between BNP and interdialytic ambulatory BP. Since interdialytic ambulatory BP is reVolume overload is the invisible threat to the health of dialysis patients. Currently, Medicare incentivizes the measurement of the dose of dialysis (urea reduction ratio) but has no measure of volume. Perhaps this is because the few who can recognize the epidemic nature of volume excess cannot agree on how to define it. Whereas, some have proposed interdialytic weight gain (IDWG) as a marker of volume, the in-depth review of Hecking et al. [1] quite clearly and importantly makes the distinction that IDWG should not be confused with hypervolemia. One has to wonder how IDWG got confused with dry weight in the first place. It appears that epidemiologists decided to use IDWG as a proxy of dry weight because of its ready availability in large databases. IDWG is a marker that is convenient; it can be measured easily and it can be related to outcomes such as all-cause mortality. This analysis was performed and a relationship emerged between IDWG and all-cause mortality. But establishing a relationship between IDWG and mortality does not establish causality. It could be numerous other factors, measured and unmeasured, associated with IDWG which may be causally related to mortality. Factors such as missing or cutting short dialysis, not taking medications as prescribed, and consuming a diet rich in phosphorus and potassium are some confounding factors that may also be associated with IDWG but may be more plausibly related to mortality. The authors discuss several markers of volume excess. Although several exist, one marker, bioimpedance analysis (BIA), is discussed in great detail. This is understandable given both the academic and intellectual property Published online: July 6, 2013 Nephrology American Journal of
24249726
Regulation of circadian blood pressure: from mice to astronauts.
PURPOSE OF REVIEW
Circadian variation is commonly seen in healthy people; aberration in these biological rhythms is an early sign of disease. Impaired circadian variation of blood pressure (BP) has been shown to be associated with greater target organ damage and with an elevated risk of cardiovascular events independent of the BP load. The purpose of this review is to examine the physiology of circadian BP variation and propose a tripartite model that explains the regulation of circadian BP.


RECENT FINDINGS
The time-keeper in mammals resides centrally in the suprachiasmatic nucleus. Apart from this central clock, molecular clocks exist in most peripheral tissues including vascular tissue and the kidney. These molecular clocks regulate sodium balance, sympathetic function and vascular tone. A physiological model is proposed that integrates our understanding of molecular clocks in mice with the circadian BP variation among humans. The master regulator in this proposed model is the sleep-activity cycle. The equivalents of peripheral clocks are endothelial and adrenergic functions. Thus, in the proposed model, the variation in circadian BP is dependent upon three major factors: physical activity, autonomic function, and sodium sensitivity.


SUMMARY
The integrated consideration of physical activity, autonomic function, and sodium sensitivity appears to explain the physiology of circadian BP variation and the pathophysiology of disrupted BP rhythms in various conditions and disease states. Our understanding of molecular clocks in mice may help to explain the provenance of blunted circadian BP variation even among astronauts.
31378323
Immunosuppressive therapy in lung injury due to paraquat poisoning: a meta-analysis.
INTRODUCTION
Immunosuppressive therapy has been shown to improve outcomes in patients with paraquat poisoning. The objective of this study was to evaluate the efficacy of immunosuppressive therapy in the management of lung injury due to paraquat poisoning.


METHODS
We searched the MEDLINE, OVID, and CINAHL databases for relevant studies published from 1980 to 2006. We included studies if (a) the study design was a randomised controlled trial, observational study with historical controls or observational study; (b) the study population included patients with paraquat poisoning, and received immunosuppressive therapy; and (c) the study provided data on mortality. We calculated the survival rate with 95 percent confidence intervals (CI) for observational studies, and relative risk and 95 percent CI for dichotomous outcomes.


RESULTS
12 studies--four non-randomised, six non-randomised comparing historical controls, and two randomised controlled trials--had employed immunosuppressive therapy in the management of paraquat poisoning. The survival rate in the four non-randomised studies (39 patients) was 74.4 percent (95 percent CI 58.9-85.4). The relative risk of immunosuppressive therapy in decreasing mortality with paraquat poisoning was 0.55 (95 percent CI 0.39-0.77) and 0.6 (95 percent CI 0.27-1.34) for the non-randomised studies (comparing historical controls) and randomised controlled studies, respectively. There was significant heterogeneity and evidence of publication bias.


CONCLUSION
One out of four patients (95 percent CI 3-5) were successfully treated with immunosuppressive therapy for paraquat poisoning. However, due to significant heterogeneity and publication bias, a large randomised controlled trial will be required to affirm the role of immunosuppression in paraquat poisoning.
22868381
Allergic bronchopulmonary aspergillosis: lessons from 126 patients attending a chest clinic in north India.
AIMS AND OBJECTIVES
To describe the experience of screening patients with asthma for allergic bronchopulmonary aspergillosis (ABPA) presenting to a chest clinic. The clinical, serologic, radiologic, and treatment aspects including outcome of ABPA are also described.


METHODS
All consecutive patients with asthma presenting to the chest clinic over a period of 2 years were screened with an Aspergillus skin test. Patients who were found to be positive were further investigated for ABPA. Patients were also arbitrarily classified as ABPA-seropositive (ABPA-S), ABPA with central bronchiectasis (ABPA-CB), and ABPA-CB with other radiologic findings (ABPA-CB-ORF) based on the high-resolution CT findings.


RESULTS
Five hundred sixty-four patients were screened using an Aspergillus skin test; 223 patients (39.5%) were found to be positive, and ABPA was diagnosed in 126 patients (27.2%). There were 34 patients (27%) with ABPA-S, 42 patients with ABPA-CB, and 50 patients with ABPA-CB-ORF. Fifty-nine patients (46.8%) had received antitubercular therapy in the past. The vast majority of patients had bronchiectasis at presentation to our hospital. High-attenuation mucous impaction was noted in 21 patients (16.7%). There was no significant difference between the stages of ABPA and the duration of illness, the severity of asthma, and the serologic findings (ie, absolute eosinophil count, IgE levels [total] and IgE levels [for Aspergillus fumigatus]). The median duration of follow-up was 13 months (range, 9 to 38 months). All patients went into "remission" at 6 weeks. Twenty-five patients had a "relapse" during the course of their treatment. One hundred nine patients had "complete remission," 17 patients were classified as having "glucocorticoid-dependent ABPA," and 7 patients were classified as having "end-stage ABPA."


CONCLUSIONS
There is a high prevalence of ABPA in asthmatic patients presenting at our hospital. The disease entity is still underrecognized in India; the vast majority of patients have bronchiectasis at presentation, and almost half are initially misdiagnosed as having pulmonary tuberculosis. There is a need to redefine the definitions of ABPA and the optimal dose/duration of glucocorticoid therapy. This study reinforces the need for the routine screening of asthmatic patients with an Aspergillus skin test.
29698466
Allergic bronchopulmonary aspergillosis.
Allergic bronchopulmonary aspergillosis (ABPA) is an immunologic pulmonary disorder caused by hypersensitivity to Aspergillus fumigatus. Clinically, a patient presents with chronic asthma, recurrent pulmonary infiltrates, and bronchiectasis. The population prevalence of ABPA is not clearly known, but the prevalence in asthma clinics is reported to be around 13%. The disorder needs to be detected before bronchiectasis has developed because the occurrence of bronchiectasis is associated with poorer outcomes. Because many patients with ABPA may be minimally symptomatic or asymptomatic, a high index of suspicion for ABPA should be maintained while managing any patient with bronchial asthma whatever the severity or the level of control. This underscores the need for routine screening of all patients with asthma with an Aspergillus skin test. Finally, there is a need to update and revise the criteria for the diagnosis of ABPA. This review summarizes the advances in the diagnosis and management of ABPA using a systematic search methodology.
33705616
Anticancer potential of silymarin: from bench to bed side.
Silymarin consists of a family of flavonoids (silybin, isosilybin, silychristin, silydianin and taxifoline) commonly found in the dried fruit of the milk thistle plant Silybum marianum. Although silymarin's role as an antioxidant and hepatoprotective agent is well known, its role as an anticancer agent has begun to emerge. Extensive research within the last decade has shown that silymarin can suppress the proliferation of a variety of tumor cells (e.g., prostate, breast, ovary, colon, lung, bladder); this is accomplished through cell cycle arrest at the G1/S-phase, induction of cyclin-dependent kinase inhibitors (such as p15, p21 and p27), down-regulation of anti-apoptotic gene products (e.g., Bcl-2 and Bcl-xL), inhibition of cell-survival kinases (AKT, PKC and MAPK) and inhibition of inflammatory transcription factors (e.g., NF-kappaB). Silymarin can also down-regulate gene products involved in the proliferation of tumor cells (cyclin D1, EGFR, COX-2, TGF-beta, IGF-IR), invasion (MMP-9), angiogenesis (VEGF) and metastasis (adhesion molecules). The antiinflammatory effects of silymarin are mediated through suppression of NF-kappaB-regulated gene products, including COX-2, LOX, inducible iNOS, TNF and IL-1. Numerous studies have indicated that silymarin is a chemopreventive agent in vivo against a variety of carcinogens/tumor promoters, including UV light, 7,12-dimethylbenz(a)anthracene (DMBA), phorbol 12-myristate 13-acetate (PMA) and others. Silymarin has also been shown to sensitize tumors to chemotherapeutic agents through down-regulation of the MDR protein and other mechanisms. It binds to both estrogen and androgen receptors, and down-regulates PSA. In addition to its chemopreventive effects, silymarin exhibits antitumor activity against human tumors (e.g., prostate and ovary) in rodents. Various clinical trials have indicated that silymarin is bioavailable and pharmacologically safe. Studies are now in progress to demonstrate the clinical efficacy of silymarin against various cancers.
13914994
Noninvasive positive pressure ventilation in acute respiratory failure due to COPD vs other causes: Effectiveness and predictors of failure in a respiratory ICU in North India
Objectives To determine the effectiveness of noninvasive positive pressure ventilation (NIPPV), and the factors predicting failure of NIPPV in acute respiratory failure (ARF) due to chronic obstructive pulmonary disease (COPD) versus other causes of ARF. Patients and methods This was a prospective observational study and all patients with ARF requiring NIPPV over a one-and-a-half year period were enrolled in the study. We recorded the etiology of ARF and prospectively collected the data for heart rate, respiratory rate, arterial blood gases (pH, partial pressure of oxygen in the arterial blood [PaO2], partial pressure of carbon dioxide in arterial blood [PaCO2]) at baseline, one and four hours. The patients were further classified into two groups based on the etiology of ARF as COPD–ARF and ARF due to other causes. The primary outcome was the need for endotracheal intubation during the intensive care unit (ICU) stay. Results During the study period, 248 patients were admitted in the ICU and of these 63 (25.4%; 24, COPD–ARF, 39, ARF due to other causes; 40 male and 23 female patients; mean [standard deviation] age of 45.7 [16.6] years) patients were initiated on NIPPV. Patients with ARF secondary to COPD were older, had higher APACHE II scores, lower respiratory rates, levels compared to other causes of ARF. After one hour there was lower pH and higher PaCO2 levels with increase a significant decrease in respiratory rate and heart rate and decline in PaCO2 levels in patients successfully managed with NIPPV. However, there was no in pH and PaO2 difference in improvement of clinical and blood gas parameters between the two groups except at one hour which was significantly the rate of decline of pH at one and four hours and PaCO2 faster in the COPD group. NIPPV failures were significantly higher in ARF due to other causes (15/39) than in ARF–COPD (3/24) (p = 0.03). The mean ICU and hospital stay and the hospital mortality were similar in the two groups. In the multivariate logistic regression model (after and adjusting for gender, APACHE II scores and improvement in respiratory rate, pH, PaO2 at one hour) only the etiology of ARF, ie, ARF–COPD, was associated with a decreased PaCO2 risk of NIPPV failure (odds ratio 0.23; 95% confidence interval, 0.58–0.9). Conclusions NIPPV is more effective in preventing endotracheal intubation in ARF due to COPD than other causes, and the etiology of ARF is an important predictor of NIPPV failure.