Furosemide impairs nasal mucociliary clearance in humans

Furosemide, a potent diuretic, affects ion and water movement across the respiratory epithelium. However, the effects of furosemide, as clinically used, on mucociliary clearance, a critical respiratory defense mechanism, are still lacking in humans. Fourteen young healthy subjects were assigned to three random interventions, spaced one-week apart: no intervention (control), oral furosemide (40 mg), and furosemide + oral volume replacement (F + R). Nasal mucociliary clearance was assessed by saccharine test (STT), and mucus properties were in vitro evaluated by means of contact angle and transportability by sneeze. Urine output and osmolality were also evaluated. Urine output increased and reduced urine osmolality in furosemide and F + R compared to the control condition. STT remained stable in the control group. In contrast, STT increased significantly (40%) after furosemide and F + R. There were no changes in vitro mucus properties in all groups. In conclusion, furosemide prolongs STT in healthy young subjects. This effect is not prevented by fluid replacement, suggesting a direct effect of furosemide on the respiratory epithelium. (C) 2010 Elsevier B.V. All rights reserved.

MEDIAL LONGITUDINAL ARCH CHANGE IN DIABETIC PERIPHERAL NEUROPATHY

Objective: To describe and compare foot anthropometry in healthy and diabetic subjects using Medial Longitudinal Arch (MLA) classificatory indexes: Arch Index (AI), Chippaux-Smirak Index (CSI) and (A) over cap Angle ((A) over cap), as well as to compare the classification of these methods in each group. Materials and Methods: Control Group (CG) composed by 21 healthy subjects and Diabetic Group (DG), with 46 diabetic neuropathy subjects. The indexes were calculated from footprints. Results: A larger proportion of flat feet was seen in DG for the three indexes (At: 32,2%, CSI: 59,7%, A: 17,5%), while highly arched feet acted oppositely. The groups were statistically different for the proportion of flat feet in (A) over cap (p=0,0080) and CSI (p=0,0000) and high feet in A (p=0,0036). There were significant differences when compared GC and GD in the three indexes: IA (p 0,0027), CSI (p=0,0064), (A) over cap (p=0,0296). Conclusion: Data showed motor and orthopedic changes originated by peripheral neuropathy, which is responsible for foot changes, causing longitudinal arch crumbling. It was seen that A Angle strongly disagreed when compared with the arch classification made by the other two indexes and therefore, its application needs care.

Proton transport model in the ionosphere .1. Multistream approach of the transport equations

The suprathermal particles, electrons and protons, coming from the magnetosphere and precipitating into the high-latitude atmosphere are an energy source of the Earth's ionosphere. They interact with ambient thermal gas through inelastic and elastic collisions. The physical quantities perturbed by these precipitations, such as the heating rate, the electron production rate, or the emission intensities, can be provided in solving the kinetic stationary Boltzmann equation. This equation yields particle fluxes as a function of altitude, energy, and pitch angle. While this equation has been solved through different ways for the electron transport and fully tested, the proton transport is more complicated. Because of charge-changing reactions, the latter is a set of two-coupled transport equations that must be solved: one for protons and the other for H atoms. We present here a new approach that solves the multistream proton/hydrogen transport equations encompassing the collision angular redistributions and the magnetic mirroring effect. In order to validate our model we discuss the energy conservation and we compare with another model under the same inputs and with rocket observations. The influence of the angular redistributions is discussed in a forthcoming paper.

Hip fracture prognosis: could bioimpedance be an alternative to conventional nutritional assessment?

Background: Risk-factors for mortality in hip fractures encompass nutritional status, nominally body mass index, but not body composition. Given the difficulty of anthropometric assessment in bedridden patients a prospective study with bioimpedance analysis was designed. Methods: Elderly patients with hip fracture were consecutively recruited. Biochemical tests, primitive bioimpedance measurements (resistance, reactance and phase angle) and follow-up till one year were targeted. Results: Patients (N = 69, 81.2 +/- 8.1 years old, 72.5% females) stayed in the hospital for 15.5 +/- 17.1 days, and 18.8 %(13/69) required further hospitalization during the ensuing months. Mortality was 11.6% within 30 days, coinciding with hospital mortality, and an additional 11.6% till one year, thus reaching 23.2%. Anemia, hypoalbuminemia and low transferrin, along with elevated glucose and urea were frequent, suggesting undernutrition with metabolic derangements. Reactance, urea and creatinine were different in patients suffering both early and late demise. Resistance, white blood cell count and osteoporosis were risk factors for early mortality only, and anemia exclusively for late mortality. Conclusions: Primitive bioimpedance measurements, which had not been hitherto investigated, were prognostically related to early and late mortality. These markers of disease-related malnutrition and especially reactance should be further studied in patients unfit for anthropometric evaluation due to fracture and immobility.

Major histocompatibility complex (MHC) class II-positive dendritic cells in the rat iris - In situ development from MHC class II-negative precursors

Purpose. To examine the postnatal development of major histocompatibility complex (MHC) class II-positive dendritic cells (DC) in the iris of the normal rat eye. Methods. Single-and double-color immunomorphologic studies were performed on whole mounts prepared from rat iris taken at selected postnatal ages (2 to 3 days to 78 weeks). Immunopositive cells were enumerated, using a quantitative light microscope, and MHC class II expression on individual cells was assessed by microdensitometric analysis. Results. Major histocompatibility class II-positive DCs in the iris developed in an age-dependent manner and reached adult-equivalent density and structure at approximately 10 weeks of age, considerably later than previously described in other DC populations in the rat. In contrast, the anti-rat DC monoclonal antibody OX62 revealed a population of cells present at adult-equivalent levels as early as 3 weeks after birth. Dual-color immunostaining and microdensitometric analysis demonstrated that during postnatal growth, development of the network of MHC class II-positive DCs was a consequence of the progressive increase in expression of MHC class II antigen by OX62-positive cells. Conclusions. During postnatal growth, the DC population of the iris develops initially as an OX62-positive-MHC class II-negative population, which then develops increasing MHC class II expression in situ and finally resembles classic DC populations in other tissue sites. Maturation of the iris DC population is temporally delayed compared with time to maturation in other tissue sites in the rat.

Additive Intraocular Pressure Reduction Effect of Fixed Combination of Maleate Timolol 0.5%/Dorzolamide 2% (Cosopt) on Monotherapy With Latanoprost (Xalatan) in Patients With Elevated Intraocular Pressure A Prospective, 4-week, Open-label, Randomized, Controlled Clinical Trial

Purpose: To evaluate the additive effect of dorzolamide/timolol fixed combination in patients under monotherapy with latanoprost. Patients and Methods: In this prospective, 4-week, randomized, open-label controlled clinical trial, patients with open-angle glaucoma or ocular hypertension, which presented at least 15% intraocular pressure (IOP) reduction after a minimum period of 15 days of monotherapy with latanoprost and whose IOP level was considered above the established target-IOP level were randomized to receive fixed combination of timolol/dorzolamide twice daily in one of eyes. The fellow eye was kept under monotherapy and was included in the control group. A modified diurnal tension curve (mDTC) followed by the water drinking test were performed in the baseline and week 4 visits to evaluate IOP profile between groups. Results: Forty-nine per-protocol patients were analyzed. After latanoprost monotherapy run-in period, IOP levels were significantly reduced (P<0.001) in both control and study groups to 15.34 +/- 2.96 mm Hg and 15.24 +/- 2.84 mm Hg (30.8% and 32.2% IOP reduction, respectively; P=0.552). At week 4, mean baseline diurnal IOP levels were 15.60 +/- 3.09 and 14.44 +/- 3.03 (7.4% difference; P=0.01). Mean baseline IOP modified diurnal tension curve peak after latanoprost run-in period were 17.47 +/- 3.68 mm Hg and 17.02 +/- 3.35 mm Hg (control and study eyes, respectively; P=0.530). At week 4 visit, mean water-drinking test peaks were significantly reduced in the study eye group in comparison with the control group: 19.02 +/- 3.81 mm Hg and 20.39 +/- 4.19 mm Hg, respectively (6.7% reduction; P=0.039). Conclusions: In our sample, dorzolamide 2%/timolol 0.5% fixed combination as add-on therapy in patients with open-angle glaucoma or ocular hypertension under monotherapy with latanoprost with IOP already in mid-teens levels may further enhance pressure reduction.

Choroidal expansion during the water drinking test

To evaluate the correlation between intraocular pressure (IOP) rise, ocular pulse amplitude (OPA), and choroidal thickness (ChT) during the water drinking test (WDT). Primary open-angle glaucoma (POAG) patients were submitted to the WDT followed by serial IOP measurements using dynamic contour tonometry (DCT), Goldman tonometry (GAT), and ChT measurements using ultrasonographic A and B-scan (USG). A control group not submitted to the test was also evaluated using DCT, GAT, and USG. Intraclass correlation coefficient (ICC) was calculated in the control group in order to assess the reproducibility of measurements. Spearman`s coefficient (rho) was used to assess the correlation between the variables. Thirty eyes were included in the study. There was a significant IOP rise during the WDT using both GAT and DCT (p < 0.001). The OPA and ChT measurements also increased significantly (p < 0.001). Spearman`s correlation between the OPA values and ChT measurements was significant and moderate (rho = 0.40, p = 0.005). The average increase of OPA and ChT measurements occurred 15 min before the IOP rise. There was a significant increase of OPA and ChT measurements followed by an IOP rise during the WDT. Increased choroidal volume due to hemodynamic forces may be enrolled in the mechanism of IOP elevation during this stress test.

An Eight-week, Multicentric, Randomized, Interventional, Open-label, Phase 4, Parallel Comparison of the Efficacy and Tolerability of the Fixed Combination of Timolol Maleate 0.5%/Brimonidine Tartrate 0.2% Versus Fixed Combination of Timolol Maleate 0.5%/Dorzolamide 2% in Patients With Elevated Intraocular Pressure

Purpose: To compare the efficacy and tolerability of the fixed combination of timolol maleate 0.5%/brimonidine tartrate 0.2% versus fixed combination of timolol maleate 0.5%/dorzolamide 2% in patients with elevated intraocular pressure (IOP) over 8 weeks. Patients and Methods: This 8-week, multicentric. interventional, randomized, open-label, parallel group study was conducted Lit 4 centers in Brazil and 1 center in Argentina. Patients with open-angle glaucoma or ocular hypertension were randomized to receive bilaterally fixed combination of brimonidine/timolol maleate 0.5% or fixed combination of dorzolamide 2%/timolol 0.5% twice daily at 8:00 AM and 8:00 PM. A modified diurnal tension curve (8:00 AM 10:30 AM, 02:00 PM, and 4:00 PM) followed by the water drinking test (WDT), which estimates IOP peak of diurnal tension curve, were performed in the baseline and week-8 visits. Adverse events data were recorded at each visit. Results: A total of 210 patients were randomized (brimonidine/timolol, n = 111; dorzolamide/timolol, n = 99). Mean baseline IOP was 23.43 +/- 3.22 mm Hg and 23.43 +/- 4.06 mm Hg in the patients treated with brimonidine/timolol and dorzolamide/timolol, respectively (P = 0.993). Mean diurnal IOP reduction after 8 weeks were 7.02 +/- 3.06 mm Hg and 6.91 +/- 3.67 mm Hg. respectively (P = 0.811). The adjusted difference between groups (analysis of covariance) Lit week 8 was not statistically significant (P = 0.847). Mean baseline WDT peak was 27.79 +/- 4.29 mm Hg in the brimonidine/timolol group and 27.68 +/- 5.46 mm Hg in the dorzolamide/timolol group. After 8 weeks of treatment, mean WDT peaks were 20.94 +/- 3.76 mm Hg (P < 0.001) and 20.98 +/- 4.19 (P < 0.001), respectively. The adjusted difference between groups (analysis of covariance) was not statistically significant (P = 0.469). No statistical difference in terms of adverse events was Found between groups. Conclusions: Both fixed combinations were capable of significantly reducing the mean diurnal IOP, mean diurnal peak, and mean WDT peak after 8 weeks of treatment. Also, both fixed combinations are well tolerated with few side effects.

Risk Factors for Visual Field Progression in Treated Glaucoma

Objective: To determine intraocular pressure (IOP)-dependent and IOP-independent variables associated with visual field (VF) progression in treated glaucoma. Design: Retrospective cohort of the Glaucoma Progression Study. Methods: Consecutive, treated glaucoma patients with repeatable VF loss who had 8 or more VF examinations of either eye, using the Swedish Interactive Threshold Algorithm (24-2 SITA-Standard, Humphrey Field Analyzer II; Carl Zeiss Meditec, Inc, Dublin, California), during the period between January 1999 and September 2009 were included. Visual field progression was evaluated using automated pointwise linear regression. Evaluated data included age, sex, race, central corneal thickness, baseline VF mean deviation, mean follow-up IOP, peak IOP, IOP fluctuation, a detected disc hemorrhage, and presence of beta-zone parapapillary atrophy. Results: We selected 587 eyes of 587 patients (mean [SD] age, 64.9 [13.0] years). The mean (SD) number of VFs was 11.1 (3.0), spanning a mean (SD) of 6.4 (1.7) years. In the univariable model, older age (odds ratio [OR], 1.19 per decade; P = .01), baseline diagnosis of exfoliation syndrome (OR, 1.79; P = .01), decreased central corneal thickness (OR, 1.38 per 40 mu m thinner; P < .01), a detected disc hemorrhage (OR, 2.31; P < .01), presence of beta-zone parapapillary atrophy (OR, 2.17; P < .01), and all IOP parameters (mean follow-up, peak, and fluctuation; P < .01) were associated with increased risk of VF progression. In the multivariable model, peak IOP (OR, 1.13; P < .01), thinner central corneal thickness (OR, 1.45 per 40 mu m thinner; P < .01), a detected disc hemorrhage (OR, 2.59; P < .01), and presence of beta-zone parapapillary atrophy (OR, 2.38; P < .01) were associated with VF progression. Conclusions: IOP-dependent and IOP-independent risk factors affect disease progression in treated glaucoma. Peak IOP is a better predictor of progression than is IOP mean or fluctuation.

Transdermal estrogen therapy effects on fibrinogen levels in women with a past history of venous thromboembolism: a pilot study

Objective: To evaluate thromboelastographic parameters and fibrinogen levels in women treated with transdermal 17 beta estradiol. Methods: 29 menopausal women with a history of venous thromboembolic disease were included. Nine patients composed the treatment (HT) group and 20 the control group. Coagulation was assessed by thromboelastography in samples of whole blood and platelet-poor plasma (PPP). The following thromboelastographic variables were measured: time for initial coagulation (R), blood clotting speed (K and the a angle), clot tensile strength (MA and G), global index of coagulation (Cl) and fibrinolysis (LY30) and fibrinogen levels. Results: There were no differences in the other parameters comparing both groups. Fibrinogen levels showed a 13.77 +/- 19.94% reduction in the HT group and a 5.51 +/- 8.09% increase in the control group after 6 months. Conclusions: Our data suggested that transdermal estrogen may not increase blood coagulability, but that it reduces fibrinogen levels in FIT women.

Femoral Head-neck Junction Deformity is Related to Osteoarthritis of the Hip

Primary or idiopathic osteoarthritis (OA) of the hip has increasingly been attributed to the presence of presumably minor femoral or acetabular deformities that are not routinely identified. The alpha angle reflects one such deformity of the femoral neck and reflects a risk for femoroacetabular impingement, which in turn reportedly is associated with OA. If impingement is in fact associated with OA, then one might expect the mean alpha angle to be greater in patients with presumed idiopathic hip OA. We therefore compared the alpha angle among a group of elderly patients with idiopathic OA with that in a control group of elderly individuals without OA. We measured the alpha angles in 50 individuals (72 hips) with a mean age of 70 years (range, 60-84 years) with apparently idiopathic OA and compared their angles with those from a control group of 56 individuals without OA. The alpha angle was measured by means of radiographs of their hips using the Dunn view at 45A degrees flexion. The patients with OA had a greater percentage with abnormal alpha angles than did the normal subjects: 82% versus 30%, respectively. The mean alpha angle in the group with OA was larger than in the control subjects: 66.4A(0) (range, 28A degrees-108A degrees) versus 48.1A(0) (range, 34A degrees-68A degrees). Hips with presumably idiopathic OA had more abnormalities at the femoral head-neck junction than did the control hips without OA and may relate to the risk of OA developing. Level II, prognostic study. See Guidelines for Authors for a complete description of levels of evidence.

Repeated stress reduces mucociliary clearance in animals with chronic allergic airway inflammation

We evaluated if repeated stress modulates mucociliary clearance and inflammatory responses in airways of guinea pigs (GP) with chronic inflammation. The GP received seven exposures of ovalbumin or saline 0.9%. After 4th inhalation, animals were submitted to repeated forced swim stressor protocol (5x/week/2 weeks). After 7th inhalation, GP were anesthetized. We measured transepithelial potential difference, ciliary beat frequency, mucociliary transport, contact angle, cough transportability and serum cortisol levels. Lungs and adrenals were removed, weighed and analyzed by morphometry. Ovalbumin-exposed animals submitted to repeated stress had a reduction in mucociliary transport, and an increase on serum cortisol, adrenals weight, mucus wettability and adhesivity, positive acid mucus area and IL-4 positive cells in airway compared to non-stressed ovalbumin-exposed animals (p < 0.05). There were no effects on eosinophilic recruitment and IL-13 positive cells. Repeated stress reduces mucociliary clearance due to mucus theological-property alterations, increasing acid mucus and its wettability and adhesivity. These effects seem to be associated with IL-4 activation. (C) 2010 Elsevier B.V. All rights reserved.

The Relationship between Intraocular Pressure Reduction and Rates of Progressive Visual Field Loss in Eyes with Optic Disc Hemorrhage

Purpose: To evaluate rates of visual field progression in eyes with optic disc hemorrhages and the effect of intraocular pressure (IOP) reduction on these rates. Design: Observational cohort study. Participants: The study included 510 eyes of 348 patients with glaucoma who were recruited from the Diagnostic Innovations in Glaucoma Study (DIGS) and followed for an average of 8.2 years. Methods: Eyes were followed annually with clinical examination, standard automated perimetry visual fields, and optic disc stereophotographs. The presence of optic disc hemorrhages was determined on the basis of masked evaluation of optic disc stereophotographs. Evaluation of rates of visual field change during follow-up was performed using the visual field index (VFI). Main Outcome Measures: The evaluation of the effect of optic disc hemorrhages on rates of visual field progression was performed using random coefficient models. Estimates of rates of change for individual eyes were obtained by best linear unbiased prediction (BLUP). Results: During follow-up, 97 (19%) of the eyes had at least 1 episode of disc hemorrhage. The overall rate of VFI change in eyes with hemorrhages was significantly faster than in eyes without hemorrhages (-0.88%/year vs. -0.38%/year, respectively, P < 0.001). The difference in rates of visual field loss pre- and post-hemorrhage was significantly related to the reduction of IOP in the post-hemorrhage period compared with the pre-hemorrhage period (r = -0.61; P < 0.001). Each 1 mmHg of IOP reduction was associated with a difference of 0.31%/year in the rate of VFI change. Conclusions: There was a beneficial effect of treatment in slowing rates of progressive visual field loss in eyes with optic disc hemorrhage. Further research should elucidate the reasons why some patients with hemorrhages respond well to IOP reduction and others seem to continue to progress despite a significant reduction in IOP levels. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references. Ophthalmology 2010; 117: 2061-2066 (C) 2010 by the American Academy of Ophthalmology.

Otitis media with effusion and dental occlusion: is there any relationship?

Aim Auditory tube dysfunction is one of the aetiological causes of otitis media. Studies suggest a correlation between otitis media with effusion and dental malocclusion. Our goal was to determine any correlation between dental malocclusion and otitis media with effusion in children with chronic upper airway obstruction due to tonsil and adenoid enlargement. Materials and methods This prospective study evaluated 52 children with otitis media with effusion and 48 without, aged 4.2 to 10.8 years. A questionnaire was answered by the parents about breast or bottle-feeding and bad oral habits. Malocclusion was diagnosed according to Angle`s classification for molar relationships in Classes I, II and III, posterior and anterior cross bite, open and deep bite, and overjet. Results and conclusion The results suggested no correlation between dental malocclusion and otitis media with effusion. Other potential confounders, such as breast or bottle-feeding and oral habits were also not correlated.

A Comparison of Rates of Change in Neuroretinal Rim Area and Retinal Nerve Fiber Layer Thickness in Progressive Glaucoma

PURPOSE. To evaluate and compare rates of change in neuro-retinal rim area (RA) and retinal nerve fiber layer thickness (RNFLT) measurements in glaucoma patients, those with suspected glaucoma, and normal subjects observed over time. METHODS. In this observational cohort study, patients recruited from two longitudinal studies (Diagnostic Innovations in Glaucoma Study-DIGS and African Descent and Evaluation Study-ADAGES) were observed with standard achromatic perimetry (SAP), optic disc stereophotographs, confocal scanning laser ophthalmoscopy (HRT-3; Heidelberg Engineering, Heidelberg, Germany), and scanning laser polarimetry (GDx-VCC; Carl Zeiss Meditec, Inc., Dublin, CA). Glaucoma progression was determined by the Guided Progression Analysis software for standard automated perimetry [SAP] and by masked assessment of serial optic disc stereophotographs by expert graders. Random-coefficients models were used to evaluate rates of change in average RNFLT and global RA measurements and their relationship with glaucoma progression. RESULTS. At baseline, 194 (31%) eyes were glaucomatous, 347 (55%) had suspected glaucoma, and 88 (14%) were normal. Forty-six (9%) eyes showed progression by SAP and/or stereophotographs, during an average follow-up of 3.3 (+/-0.7) years. The average rate of decline for RNFLT measurements was significantly higher in the progressing group than in the non-progressing group (-0.65 vs. -0.11 mu m/y, respectively; P < 0.001), whereas RA decline was not significantly different between these groups (-0.0058 vs. -0.0073 mm(2)/y, respectively; P = 0.727). The areas under the receiver operating characteristic (ROC) curves used to discriminate progressing versus nonprogressing eyes were 0.811 and 0.507 for the rates of change in the RNFLT and RA, respectively (P < 0.001). CONCLUSIONS. The ability to discriminate eyes with progressing glaucoma by SAP and/or stereophotographs from stable eyes was significantly greater for RNFLT than for RA measurements. (Invest Ophthalmol Vis Sci. 2010;51:3531-3539) DOI: 10.1167/iovs.09-4350