24288835
Toward a definition of masked hypertension and white-coat hypertension among hemodialysis patients.
BACKGROUND AND OBJECTIVES
Among people with essential hypertension, ambulatory BP measurement is superior to BP obtained in the clinic in predicting cardiovascular outcomes. In part, this is because it can detect white-coat hypertension and masked hypertension. Whether the same is true for hemodialysis patients is not known.


DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS
Using a threshold of 140/80 mmHg for median midweek dialysis-unit BP and 135/85 mmHg for 44-hour ambulatory BP, we defined four categories of BP: sustained normotension (SN), white-coat hypertension (WCH), masked hypertension (MHTN), and sustained hypertension (SHTN).


RESULTS
Among 355 long-term hemodialysis patients, the prevalence of SN was 35%, WCH 15%, MHTN 15%, and SHTN 35%. Over a mean follow-up of 29.6 (SD 21.7) months, 102 patients died (29%), yielding a crude mortality rate of 121/1000 patient-years. Unadjusted and multivariate-adjusted analyses showed increasing all-cause mortality with increasing severity of hypertension (unadjusted hazard ratios from SN, WCH, MHTN, SHTN: 1, 1.12, 1.70, 1.80, respectively [P for trend < 0.01]; adjusted hazard ratios: 1, 1.30, 1.36, 1.87, respectively [P for trend 0.02]). When a predialysis BP threshold of 140/90 mmHg was used to classify patients into BP categories, the prevalence of SN was 24%, WCH 26%, MHTN 4%, and SHTN 47%. Hazard ratios for mortality were similar when compared with median midweek dialysis-unit BP.


CONCLUSIONS
As in the essential hypertension population, MHTN and WCH have prognostic significance. The prognostic value of BP obtained in the dialysis unit can be refined with ambulatory BP monitoring.
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.
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
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.
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.
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.
11872305
Low dose of snake antivenom is as effective as high dose in patients with severe neurotoxic snake envenoming
The objective of this study was to evaluate the effects of two different dosage protocols on the outcome of patients with severe neurotoxic snake envenoming, using a retrospective analysis of patients admitted with a diagnosis of severe neurotoxic snake bite over a 4 year period. In the study, 55 snake bite victims requiring ventilatory support for severe neurotoxic envenoming received either 150 ml of polyvalent snake antivenom (SAV) (low dose SAV group, n = 28) or 100 ml of SAV at presentation followed by 100 ml every 6 hours until recovery of neurological manifestations (high dose group, n = 27). The median dose of SAV in the high dose group was 600 ml (range 300 to 1600). The duration of mechanical ventilation in the low dose group (median 47.5 hours; range 14 to 248) was similar to that in the high dose group (median 44 hours; range 6 to 400). The mean (SD) duration of intensive care unit stay was similar in the two groups. There were three deaths in the high dose group; two patients in the low dose group had neurological sequelae. All other patients improved, had no residual neurological deficit, and were discharged. We conclude that there is no difference between a protocol using lower doses of SAV and one with higher doses in the management of patients with severe neurotoxic snake envenoming.
39024721
Efficacy and safety of iodopovidone in chemical pleurodesis: a meta-analysis of observational studies.
The search for an 'ideal' agent for pleurodesis continues. Iodopovidone is a topical antiseptic and has been shown to be safe and effective in many studies. The aim of this study was to evaluate the efficacy and safety of iodopovidone as an agent for chemical pleurodesis. We performed a systematic review of all the observational trials which have used iodopovidone for chemical pleurodesis. Six studies including 265 patients who had undergone chemical pleurodesis with iodopovidone were included for this analysis. Iodopovidone was used for variety of indications, which included pleural effusion (157 patients), and pneumothorax (108 patients). Pleurodesis was performed through tube thoracostomy in 144 patients and through thoracoscopy in 121 patients. The success rate of pleurodesis varied from 64.2% to 100%, and summary success rate of all the studies was 90.6% (95% confidence intervals [CI], 86.4-93.8). The success rate was independent for the procedure (tube thoracostomy [126/144; 87.5%, 95% CI 80.9-92.4] or thoracoscopy [114/121; 94.2%, 95% CI 88.4-97.6]) used for performing pleurodesis or for the indication (pleural effusion [139/157; 88.5%, 95% CI 82.5-93.1] or pneumothorax [101/108; 93.5%, 95% CI 87.1-97.4]). The only significant complication reported was chest pain of varying degree. Systemic hypotension was reported in three patients in only one study. There were no deaths related to chemical pleurodesis with iodopovidone. Overall, this review supports the safety and efficacy of iodopovidone as an agent for chemical pleurodesis in cases of recurrent pleural effusions and pneumothoraces regardless of their etiology.
35489466
Aspergillus hypersensitivity and allergic bronchopulmonary aspergillosis in patients with bronchial asthma: systematic review and meta-analysis.
BACKGROUND
The prevalence of Aspergillus hypersensitivity (AH) and allergic bronchopulmonary aspergillosis (ABPA) in bronchial asthma is reported differently in various studies.


OBJECTIVE
To determine the prevalence of AH and ABPA in asthma using a systematic review.


METHODS
We searched the MEDLINE and EMBASE databases for studies published from 1965 to 2008 and included studies that report the prevalence of AH/ABPA in asthma. We calculated the proportions with 95% confidence interval (CI) to assess the prevalence of AH/ABPA in the individual studies and pooled the results using a random effects model.


RESULTS
Our search yielded 21 eligible studies. The prevalence of AH in bronchial asthma was 28% (95%CI 24-34), and was higher with an intradermal test vs. a prick test (28.7% vs. 24.8%, P = 0.002), but did not vary with the type of antigen used (indigenous or commercial). The prevalence of ABPA in bronchial asthma and Aspergillus-hypersensitive bronchial asthma was respectively 12.9% (95%CI 7.9-18.9) and 40% (95%CI 27-53). There was a wide variation in the criteria used for the diagnosis of ABPA. There was significant statistical heterogeneity assessed by the I(2) test and Cochran Q statistic in all the outcomes.


CONCLUSIONS
There is a high prevalence of AH and ABPA in patients with bronchial asthma. Careful screening should therefore be performed in all patients with bronchial asthma. Intradermal tests are more sensitive than prick tests for the diagnosis of AH. Finally, there is a need to adopt a uniform methodology and criteria for the diagnosis of AH/ABPA.
45424950
It is time to "SALVAGE" patients with severe sepsis.
25550116
Noninvasive estimation of clinically asymptomatic pulmonary hypertension in idiopathic pulmonary fibrosis.
OBJECTIVES
To determine the prevalence of pulmonary hypertension in patients with idiopathic pulmonary fibrosis (IPF) by noninvasive methods.


PATIENTS AND METHODS
Twenty seven patients with IPF attending the Chest Clinic over a period of one-and-a-half-years underwent echocardiography for evidence of pulmonary hypertension, which was defined as pulmonary artery systolic pressure > or = 40 mmHg by Doppler echocardiography, or pulmonary acceleration time < or = 100 milliseconds or two-dimensional echocardiographic findings of right ventricular hypertrophy or overload.


RESULTS
Two patients with clinical evidence of pulmonary hypertension were excluded from analysis. Their mean age (n = 25) was 53.8 years. The mean duration of symptoms before presentation was 2.1 years. Pulmonary hypertension was diagnosed by echocardiography in nine of the 25 patients (36%). There was a statistically significant difference between the duration of illness, arterial oxygen tension (PaO2) levels and forced vital capacity in patients with pulmonary hypertension than in those without pulmonary hypertension. Logistic regression analysis showed a significant association between the duration of illness, decreasing forced vital capacity and hypoxemia with the development of pulmonary hypertension.


CONCLUSIONS
Echocardiography detects pulmonary hypertension in clinically asymptomatic individuals, and should be used routinely for the diagnosis of pulmonary hypertension in patients with IPF.