44772256
The septospinal ligament in cleft lip nose deformity: study in adult unilateral clefts.
BACKGROUND
Septal deviation and alar cartilage deformities constitute an important component of both the aesthetic deformity and airway compromise in unilateral cleft lip nose deformity. The purpose of this study was to examine the retrocolumellar preseptal area in this deformity for evaluation of deforming forces in the adult population.


METHODS
Fifty-five patients aged 13 years or older presenting with unilateral cleft nasal deformity were included. The caudal border of the septum was accessed using an incision along the ipsilateral membranous septum. Perioperatively, the curved caudal septal edge was exposed and explored down to its attachment with the hypertrophied anterior nasal spine. The overlying tethering tissues were excised and submitted for histopathologic examination. The curved septal cartilage was straightened and the misplaced anterior nasal spine was excised. The remaining cleft nasal deformity was corrected depending on the specific presenting pathologic abnormality.


RESULTS
A well-defined, tough, fibrous band was detected extending from the deviated curved surface of the septal cartilage to the anterior nasal spine that was filling up the retrocolumellar area. Histopathologic examination revealed fibrous tissue in all cases studied, consistent with diagnosis of a ligament. Postoperatively, the nasal tip complex cosmetic result was considered to be good or very good in 89.7 percent, satisfactory in 8.1 percent, and poor in 2.0 percent of patients.


CONCLUSIONS
A well-defined ligament has been documented and demonstrated in adult patients with unilateral cleft lip nose deformity. The authors recommend that this septospinal ligament, previously unreported, should be excised in toto to achieve straightening of the septum, columellar centralization, and nasal sill symmetry in unilateral cleft lip nose deformity.
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.
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
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.
1043
Cotyledonoid leiomyoma and non-descent vaginal hysterectomy
We read with deep interest the article by Driss et al. [1] who emphasize the association of a cotyledonoid dissecting leiomyoma with endosalpigiosis. Cotyledonoid dissecting leiomyoma is an extremely rare variant of uterine leiomyoma with just 24 cases on record [2]. Clinicoradiological diVerentiation from leiomyoma is diYcult, and diagnosis is most often not suspected preoperatively. Imaging modalities oVer no help, and its bizarre macroscopic shape may be confused with malignant neoplasm [3]. We would like to share the intraoperative Wndings of cotyledonoid dissecting leiomyoma in a 52-year-old multiparous woman during a non-descent vaginal hysterectomy (NDVH). The patient had presented with polymenorrhagia for 6 months. She had Wrst degree cervical descent with uniformly enlarged anteverted uterus of size corresponding to 8 weeks. Ultrasound evaluation was suggestive of multiple subserous Wbroid of size 6 £ 7 cm with slight Xuid in peritoneal cavity. During NDVH performed for symptomatic polymenorrhagia, after bisection we attempted to visu-
25120038
Chest radiographic and computed tomographic manifestations in allergic bronchopulmonary aspergillosis.
AIM
To investigate the chest radiographic and high resolution computed tomography (HRCT) chest manifestations in glucocorticoid-naïve allergic bronchopulmonary aspergillosis (ABPA) patients.


METHODS
This is a prospective observational study and includes 60 consecutive glucocorticoid-naïve patients with ABPA who underwent chest radiography and HRCT of the chest (1.25 mm every 10 mm) in the routine diagnostic workup for ABPA.


RESULTS
Chest radiographs were normal in 50% of cases. Of the remainder, most patients demonstrated permanent findings in the form of parallel line and ring shadows suggesting bronchiectasis. Consolidation was detected in 17 cases but in the majority, the corresponding HRCT chest scan showed mucus-filled bronchiectatic cavities. Chest HRCT was normal in 22 patients, while central bronchiectasis (CB) was demonstrated in the remaining 38 patients. Bronchiectasis extended to the periphery in 33%-43% depending on the criteria used for defining CB. The other findings observed on HRCT were mucoid impaction, centrilobular nodules and high-attenuation mucus in decreasing order of frequency.


CONCLUSION
Patients with ABPA can present with normal HRCT chest scans. Central bronchiectasis cannot be considered a characteristic feature of ABPA as peripheral bronchiectasis is commonly observed. Consolidation is an uncommon finding in ABPA.
21512706
Experience with ARDS caused by tuberculosis in a respiratory intensive care unit
ObjectiveAcute respiratory distress syndrome (ARDS) is an important cause of morbidity and mortality in intensive care units. Tuberculosis (TB) commonly causes respiratory failure in patients with extensive pulmonary parenchymal involvement, but it is a rare cause of ARDS. We report our experience of TB presenting with ARDS.MethodsRetrospective analysis of 187 patients admitted with a diagnosis of ARDS over the previous 7 years. Data are presented in a descriptive fashion using mean±SD or median (range).ResultsNine (4.9%) of 187 patients had ARDS secondary to tuberculosis. All patients were mechanically ventilated. The diagnosis was made on clinico-radiological grounds and confirmed later using fiberoptic bronchoscopy and transbronchial biopsy in seven patients, and lymph node biopsy and examination of the joint aspirate in the remaining two. All patients were empirically started on anti-tubercular therapy with a median time to initiation of therapy being 3 days (range 2–8 days). Three patients had multi-organ dysfunction syndrome (MODS) without any evidence of bacterial infection. Seven of nine (77.8%) patients survived; two died because of severe ARDS, MODS, and respiratory failure.ConclusionsTuberculosis is an uncommon but definite cause of ARDS, and in patients with ARDS of obscure aetiology where the clinical features suggest tuberculosis as the inciting cause, antitubercular therapy should be started empirically and the diagnosis actively pursued later.
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.
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.