22856684
Prediction of hypertension in chronic hemodialysis patients.
BACKGROUND
There are no universally accepted criteria for the diagnosis of hypertension in hemodialysis (HD) patients. We sought to determine the clinical performance of predialysis and postdialysis systolic and diastolic blood pressure values (BPs) in diagnosing hypertension or assessing its control.


METHODS
Seventy patients [77% African American, 46% females, mean age 59 +/- 17 (SD) years, 34% diabetics] on chronic HD underwent a single 44-hour interdialytic ambulatory blood pressure monitoring (ABPM) and concomitant recording of BP by conventional syphygmomanometer in the HD unit for two weeks. Hypertension was defined as systolic BP (SBP) > or =135 mm Hg or diastolic BP (DBP) > or =85 mm Hg on an average 44-hour ABPM.


RESULTS
Average ABP was 144 +/- 22/81 +/- 11 mm Hg. Seventy-three percent of the patients had systolic hypertension; 40% had diastolic hypertension, and 24% were normotensive or had well-controlled BP. Area under the curve of receiver operating characteristic (ROC) curves exceeded 80% for all BPs, but the thresholds for best sensitivity and specificity were markedly different for predialysis and postdialysis BPs. A two-week averaged predialysis BP of > 150/85 mm Hg or a postdialysis BP of > 130/75 mm Hg had at least 80% sensitivity in diagnosing hypertension. Specificity of at least 80% was achieved if predialysis BP of > 160/90 mm Hg or postdialysis BP of > 140/80 mm Hg was used. There was poor agreement between HD unit BP and ABP values.


CONCLUSIONS
HD unit BP values can be used to identify the presence or absence of hypertension, although prediction of ambulatory BPs from HD unit BP values cannot be made reliably in individual patients.
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.
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.
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.
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.
23395637
Clinical relevance of peripheral blood eosinophil count in allergic bronchopulmonary aspergillosis.
BACKGROUND AND AIMS
Currently, there is not a uniform consensus regarding the number of criteria or specific cut-off values for the variety of tests that are used to diagnose allergic bronchopulmonary aspergillosis (ABPA). Traditionally, an eosinophil count >1000 cells/μl is considered an important criterion in the diagnosis of ABPA. The goal of this study was to delineate the significance of the peripheral blood eosinophil count in the diagnosis of ABPA, and the relationship between eosinophil counts and lung function and immunological and radiological parameters.


METHODS
This study was a retrospective analysis of the data from ABPA patients who were managed in our chest clinic. Based on their eosinophil count, the patients were classified into the following three categories: <500, 500-1000 and >1000 cells/μl. The spirometric, immunological and radiological characteristics were also assessed.


RESULTS
We studied 108 males and 101 females with a combined mean (±SD) age of 34.1±12.5years. The median (IQR) eosinophil count at diagnosis was 850 (510-1541)cells/μl, and 60% of the patients had an eosinophil count of <1000 cells/μl. We found no relationship between eosinophil count and lung function using spirometry and other immunological parameters. The median eosinophil count was higher in patients with an high resolution computed tomography (HRCT) chest finding of bronchiectasis (986 vs. 620, p<0.001) vs. those without and in patients with high-attenuation mucus (1200 vs. 800, p<0.001) compared to those without high-attenuation mucus.


CONCLUSIONS
A peripheral blood eosinophil count has limited utility in the diagnosis of ABPA, and there is no relationship between eosinophil count and lung function or other immunological parameters. The higher eosinophil count that we observed in patients with central bronchiectasis or high-attenuation mucus suggests that eosinophils are primary mediators of inflammatory activity in ABPA.
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.
30259650
Cell signaling and regulators of cell cycle as molecular targets for prostate cancer prevention by dietary agents.
Prostate cancer (PCA) is the most common invasive malignancy and leading cause (after lung) of cancer deaths in males. Since PCA is initially androgen-dependent, strategies are targeted toward androgen depletion for its control. However, tumor re-growth mostly occurs following this modality, and is androgen-independent. A loss of functional androgen receptor and an enhanced expression of growth factor receptors (e.g. erbB family members) and associated ligands have been shown to be the causal genetic events in PCA progression. These genetic alterations lead to an epigenetic mechanism where a feed-back autocrine loop between membrane receptor (e.g. epidermal growth factor receptor [erbB1] and associated ligand (e.g. transforming growth factor-alpha) results in an enhanced activation of extracellular signal-regulated protein kinase 1/2 (ERK1/2) as an essential component of the uncontrolled growth of PCA at an advanced and androgen-independent stage. Together, we rationalized that inhibiting these epigenetic events would be useful in controlling advanced PCA growth. Dietary polyphenolic flavonoids and isoflavones are being studied extensively as cancer-preventive and interventive agents. Therefore, we focused our attention on silymarin, genistein, and epigallocatechin 3-gallate (EGCG), present in milk thistle, soy beans, and green tea, respectively. The effect of these agents was assessed on the erbB1-Shc-ERK1/2 signal transduction pathway, cell cycle regulatory molecules, and cell growth and death. In androgen-independent human prostate carcinoma DU145 cells, silymarin, genistein, and EGCG resulted in a significant to complete inhibition of transforming growth factor-alpha-caused activation of membrane receptor erbB1 followed by inhibition of downstream cytoplasmic signaling target Shc activation and a decrease in its binding with erbB1, without an alteration in their protein expression. Silymarin and genistein also inhibited ERK1/2 activation, suggesting that these agents impair the activation of erbB1-Shc-ERK1/2 signaling in DU145 cells. In the case of EGCG, a further increase in ERK1/2 activation was observed that was related to its pro-oxidant and apoptotic activities. Silymarin, genistein, and EGCG also resulted in a significant induction of Cip1/p21 and Kip1/p27 and a decrease in cyclin-dependent kinase (CDK) 4, but a moderate inhibition of CDK2, cyclin D1, and cyclin E was observed. An enhanced level of Cip1/p21 and Kip1/27 also led to an increase in their binding to CDK4 and CDK2. Treatment of cells with silymarin, genistein, and EGCG also resulted in strong cell growth inhibition at lower doses, and complete inhibition at higher doses. In contrast to silymarin, higher doses of genistein also showed cell death. A more profound cytotoxic effect was observed in the case of EGCG, with strong cell death at lower doses and complete loss of viability at higher doses. Together, these results suggest that cell signaling and regulators of cell cycle are potential epigenetic molecular targets for prostate cancer prevention by dietary agents. More studies, therefore, are needed with these agents to explore their anticarcinogenic potential against human prostate cancer.
24550143
Serologic allergic bronchopulmonary aspergillosis (ABPA-S): long-term outcomes.
BACKGROUND AND AIM
ABPA is radiologically classified on the presence or absence of central bronchiectasis (CB) as ABPA-CB and serologic ABPA (ABPA-S) respectively. Few studies have described the follow-up of patients with ABPA-S. The aim of this retrospective study was to describe the outcomes of ABPA-S.


METHODS
Patients were diagnosed as ABPA-S if they met all the following criteria: asthma, immediate cutaneous hyperreactivity to Aspergillus fumigatus antigen, total IgE levels >1000 IU/mL, A. fumigatus specific IgE levels >0.35 kUA/L and normal HRCT of the chest. They were treated with glucocorticoids and followed up with history, physical examination, chest radiograph and total IgE levels every 6 weeks to 3 months. In addition, an annual spirometry and a biennial HRCT chest were performed in all patients.


RESULTS
Of the 55 patients with ABPA-S, 41 (17 men, 24 women; mean age, 38.3 years) consented for performance of repeat HRCT scans. The median duration of asthma prior to diagnosis of ABPA was six years. The duration of follow-up ranged from 24 to 77 months with the mean (SD) follow-up duration being 43.7 (10.1) months. There was improvement in FEV(1) but not the FVC values during the follow-up period (p values = 0.001 and 0.5 for FEV(1) and FVC respectively). There was no development of CB in any patient. Sixteen patients had a relapse during the follow-up period, and six patients were classified as glucocorticoid-dependent ABPA.


CONCLUSIONS
Although relapses are frequently seen, the long-term outcome of ABPA-S is good with no patient developing CB.
45018613
Noninvasive ventilation in acute neuromuscular respiratory failure due to myasthenic crisis: case report and review of literature
A 30 year old male, a follow up case of myasthenia gravis, presented to the Emergency Department with complaints of sore throat, followed by increasing weakness in both the upper limbs and lower limbs. He also gave history of worsening bulbar weakness and progressive dyspnea on exertion. Two years ago the patient had undergone thymectomy. However, following thymectomy, the patient had minimal improvement in symptoms and was continued on glucocorticoids and pyridostigmine. Presently he was on prednisolone 30 mg/day and pyridostigmine 60 mg six times a day. On examination, he was conscious and afebrile with a pulse rate of 96 beats/minute, blood pressure 110/80 mm Hg and respiratory rate of 26/minute. Neurological examination revealed ptosis, dysphonia, bilateral asymmetric extra-ocular muscle weakness, and bifacial weakness. He had a single breath count of 10 and a breath holding time of 12 seconds. Pulse oximetry revealed a saturation of 87% breathing room air. Arterial blood gases were performed, which confirmed hypercapnic respiratory failure (pH 7.3, PaO2 6.9 kPa, PaCO2 6.7 kPa, HCO3 26 mEq/L). The patient was started on supplemental …