11856758
B-type natriuretic peptide is not a volume marker among patients on hemodialysis.
BACKGROUND
Although the cardiac biomarker B-type natriuretic peptide (BNP) is strongly related to mortality in end-stage renal disease (ESRD), whether it is a predictor of weight change or blood pressure (BP) response upon probing dry weight among hypertensive hemodialysis patients remains unknown. The purpose of this study was to examine among people with hypertension on hemodialysis whether BNP is a biomarker of excess volume.


METHODS
Hypertensive hemodialysis patients (n = 150) were randomized to a control group (n = 50) or an ultrafiltration group (n = 100) and followed up for 30 dialysis treatments. After a baseline run-in of six treatments, those assigned to the ultrafiltration group had dry weight probed over 8 weeks. Forty-four-hour interdialytic ambulatory BP and predialysis BNP were measured at the end of run-in period, at 4 weeks and at 8 weeks.


RESULTS
The median BNP concentration was 93 pg/mL (interquartile range 31-257 pg/mL). The magnitude of decline in the BNP depended on the baseline concentration of BNP, but did not require probing dry weight or weight loss. No relationship existed between decline in postdialysis weight upon probing dry weight and baseline BNP. Furthermore, reduction in the BNP was not required for decline in postdialysis weight. Predialysis log BNP modestly predicted ambulatory systolic and pulse pressure independently of other risk factors. No relationship was found between decline in BP upon probing dry weight and baseline BNP. Upon probing dry weight, reduction in BNP was not required for decline in systolic ambulatory BP.


CONCLUSION
Taken together, these data suggest that among hypertensive patients on hemodialysis BNP is not a volume marker.
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
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.
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.
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.
27402652
Primary peritoneal carcinoma: a diagnostic dilemma
We read with deep interest the report by Bhuyan et al. [1] detailing diagnosis and management aspects of extra ovarian primary peritoneal carcinoma (EOPPC). Indeed the clinician is intrigued by the presentation of EOPPC and equally challenging is the management because of limited guidance available in literature with these tumours. We recently diagnosed EOPPC in a 62-year-old lady and would like to share the atypical presentation of the carcinoma. This patient had received six cycles of chemotherapy (paclitexal and cisplatin) for papillary adenocarcinoma. At prior exploratory laparotomy, there was an inoperable mass adherent to transverse colon serosa with liver metastasis. As no primary site of tumour was discernable, biopsies from peritoneum and peritoneal washings were taken revealing papillary adenocarcinoma. Post chemotherapy, computed tomography scan showed resolution of ascitis, normal-sized bilateral adnexa and uterus; however, omental thickening and liver metastasis still persisted. Serum CA125 level decreased from 200 to 17.5 IU/ml. At subsequent debulking laparotomy, there was no free Xuid in abdomen but a large desmoplastic transverse colon [2] was seen. The uterus with bilateral adnexa was normal in size and shape; however, multiple hard peritoneal deposits ranging 1–10 cm in size were present in the mesentery, inWltrating up to the wall of transverse colon. Panhysterectomy and resection of transverse colon mass was done. The second laparotomy again could not reveal the primary site of tumour. Repeated histopathology of colonic segment showed serous papillary adenocarcinoma with numerous psammoma bodies inWltrating serosa and reaching up to muscularis propria. Both ovaries showed superWcial cortical involvement by the same tumour (Figs. 1, 2). Serosal aspect of both fallopian tubes, mesentery and parametrium were also studded with the same tumour. Since the gynaecologic oncology group criteria were fulWlled in our case, a diagnosis of EOPPC was rendered [3]. In our case, positive immunostaining for pan-cytokeratin (CK) and estrogen receptor, and negative staining for calretinin further supported the
44909639
Do glucocorticoids decrease mortality in acute respiratory distress syndrome? A meta-analysis.
BACKGROUND AND OBJECTIVES
Glucocorticoids have been shown to improve survival when used in patients with septic shock. The aim of this study was to analyse the role of glucocorticoids in decreasing mortality in acute respiratory distress syndrome (ARDS) both in the acute and the fibroproliferative phases.


METHODS
We searched the MEDLINE database for relevant studies published between 1980 and 2006, and included studies if the study design was a randomized controlled trial or observational study (comparing historical controls). The study population included patients with ARDS treated with glucocorticoids. We calculated the odds ratio and 95% confidence intervals (CI) for the outcome of mortality.


RESULTS
Six trials met the inclusion criteria; three investigated the role of steroids in early stage disease (n = 300) and three investigated the role of steroids in late stage disease (n = 235). The odds of glucocorticoids decreasing mortality in patients with early ARDS were 0.57 (95% CI: 0.25-1.32) with a number needed to treat of 10 for benefit (818 harm to 5 benefit) whereas the odds of glucocorticoids decreasing mortality in patients with late ARDS was 0.58 (95% CI: 0.22-1.53) with a number needed to treat of 15 for harm (6 harm to 21 benefit). However, there was significant heterogeneity.


CONCLUSIONS
Current evidence does not support a role for corticosteroids in the management of ARDS in either the early or late stages of the disease. More research is required to establish the role of steroids in specific subgroups of patients with severe sepsis and early ARDS who have relative adrenal insufficiency and patients with late ARDS 7-14 days after the onset of disease.
14241795
Role of inhaled corticosteroids in the management of serological allergic bronchopulmonary aspergillosis (ABPA).
BACKGROUND AND AIM
The treatment of choice for allergic bronchopulmonary aspergillosis (ABPA) is oral corticosteroids (OCS). However, they are associated with numerous adverse effects. Inhaled corticosteroids (ICS) are associated with fewer side-effects; however, their role in the management of ABPA remains controversial. In this retrospective study, we evaluate the role of high doses of ICS in serological ABPA (ABPA-S).


METHODS
Patients with ABPA-S were treated with a combination of formoterol/budesonide (24-1600 micrograms per day), and followed up with history, physical examination, chest radiograph and total IgE levels at 6, 12, 18 and 24 weeks. Asthma control was evaluated using the Global Initiative for Asthma (GINA) criteria. OCS were initiated if the IgE levels continued to rise after six months of therapy with ICS.


RESULTS
There were 8 men and 13 women with a mean (SD) age of 39.3 (12.9) years. There was subjective improvement in all patients treated with ICS but none had complete control of asthma. After six months of therapy with ICS, the median IgE levels increased by 99.3%. After the initiation of OCS, there was complete resolution of asthma symptoms in 19 patients, and IgE levels fell by a median of 52.6% at six weeks. The median duration of follow-up was 15 months after OCS therapy. Eighteen patients achieved complete remission and three patients had a relapse in the first three months after stopping OCS. One patient required long-term OCS and was classified as glucocorticoid-dependent ABPA.


CONCLUSION
High doses of ICS alone have no role in the management of ABPA-S and should not be used as first-line therapy. In patients receiving OCS or alternate therapy, ICS can be used as an add-on therapy for the control of symptoms of asthma.
42552241
Case report: A rare cause of miliary nodules -- allergic bronchopulmonary aspergillosis.
Allergic bronchopulmonary aspergillosis (ABPA) is a complex immune hypersensitivity reaction to the fungus Aspergillus fumigatus, which occurs in patients with asthma and cystic fibrosis. The common radiological findings include fleeting pulmonary opacities, bronchiectasis and mucoid impaction. Uncommon radiological findings encountered in ABPA include lung masses, perihilar opacities simulating hilar adenopathy and pleural effusions. Herein, we describe a 36-year-old man who presented to the chest clinic with miliary nodules on a chest radiograph and was diagnosed as having ABPA confirmed on both serology and lung biopsy. This is the first report of ABPA presenting as randomly scattered nodules on CT.
11307916
Clinical significance of decline in serum IgE levels in allergic bronchopulmonary aspergillosis.
BACKGROUND AND AIMS
The total serum IgE level is a marker of immunological activity in allergic bronchopulmonary aspergillosis (ABPA), and a 35% decline beyond six weeks is traditionally taken as criteria for remission. The aim of this study was to evaluate the magnitude and clinical significance of decline in serum IgE levels at six weeks in patients with ABPA.


METHODS
All consecutive patients with ABPA presenting to the Chest Clinic were followed up with clinical evaluation, total IgE levels and chest x-ray every six weeks for three months. We analyzed the percentage decline in IgE levels and correlated it with clinical outcomes of relapse and complete remission.


RESULTS
Of the 242 asthmatics, 54 were diagnosed with ABPA (29 males, 25 females; mean age-34 years). There was clinical and radiological improvement at six weeks in all patients receiving glucocorticoid therapy. The IgE levels fell by a mean of 38.8%, and the decline was significantly higher in patients with baseline IgE levels >2500IU/mL than with levels <or=2500IU/mL (44% vs. 26%). Twenty-two patients did not attain a 35% decline in IgE levels, and this number was significantly higher in patients with IgE levels <2500IU/mL. On multivariate analysis, the decline in IgE levels at six weeks did not predict clinical outcomes.


CONCLUSIONS
A 35% decline in serum IgE levels at six weeks is not seen in all patients with ABPA, and the decline is slower in patients with baseline IgE levels <2500IU/mL. The quantum decline in serum IgE levels does not predict clinical outcomes.