bluuebunny/crossref_metadata_2025 huggingface dataset:
Bevacizumab and ranibizumab treatments for neovascularization from causes other than age‐related macular degeneration
Authors: AZIZ S , BANERJEE S
Published: September 2009

Purpose To report the results of intravitreal bevacizumab (Avastin) and ranibizumab (Lucentis) treatment for ocular neovascularization from causes other than age‐related macular degeneration.

Methods We performed a retrospective case note analysis of eyes who received intravitreal bevacizumab and ranibizumab for patients with ocular neovascularization. Repeated treatment occurred if there were signs of recurrence of disease activity. The main outcome measures were visual acuity, clinical signs and findings on optical coherence tomography and fluorescein angiography.

Results Nine patients (10 eyes) were included in this study. Diagnoses included subfoveal choroidal neovascularization secondary to punctate inner choroidopathy (n=2), myopic degeneration (n=2), pseudoxanthoma elasticum (n=1). Others have proliferative diabetic retinopathy (n=2), central retinal vein occlusion (n=1), clinically significant macular oedema (n=1), Coat’s disease (n=1). The range of baseline visual acuity was from counting fingers to 6/9. The mean fellow‐up was 12 months; the mean number of injections in 9 eyes was 1.5. One eye had 12 injections. At the last fellow‐up, 9 eyes had improved or stable visual acuity. There were no complications reported.

Conclusion Ocular neovascularization secondary to non AMD causes treated with intravitreous bevacizumab and ranibizumab responded favourably, despite varying underlying aetiologies.
Complex regulation of choroidal blood flow during combined changes in blood pressure and IOP
Authors: SCHMETTERER L
Published: September 2009

Purpose In the recent years it has been shown that the human choroid shows some regulatory capacity during an artifical increase in intraocular pressure (IOP) as well as during an exercise induced increase in mean arterial pressure (MAP). The purpose of the present study was to test the hypothesis that human choroidal blood flow (ChBF) may depend, not only on ocular perfusion pressure (OPP), but also on absolute levels of MAP and IOP.

Methods In a clinical study in 28 helathy subjects OPP was varied by elevating IOP during a squatting‐induced increase in MAP. IOP was raised in stepwise increments by using the suction cup method. Subfoveal choroidal blood flow (VhBF, laser Doppler flowmetry), MAP, and IOP were assessed, and OPP was calculated as (2/3)(MAP ‐ IOP). For correlation analysis, data from all subjects were pooled according to IOP and MAP values, and correlation analyses were performed.

Results When data were grouped according to IOP, no correlation was observed between ChBF and MAP; but ChBFs were lower, the higher the IOP (P < 0.001). When data were grouped according to MAP, a significant correlation was found between ChBF and IOP (P < 0.001), but correlations were independent of MAP.

Conclusion These data confirm previously published observations that the choroid shows some regulatory capacity during changes in OPP. In addition, the data indicate that the choroid regulates its blood flow better during exercise‐induced changes in MAP than during an experimental increase in IOP.
Subfoveal choroidal blood flow and central retinal function in retinitis pigmentosa
Authors: FALSINI B
Published: September 2009

Abstract not provided
Comparison of Spectralis Fourier‐domain optical coherence tomography (OCT) and time‐domain Stratus OCT for the evaluation of macular thickness in patients with diabetes mellitus type 2
Authors: GIL ARRIBAS L , IDOIPE M , GARCIA MARTIN E , PINILLA I , FUERTES I
Published: September 2009

Purpose To compare spectralis fourier‐domain OCT with Stratus Time‐Domain OCT for measuring macular thickness in patients with diabetes mellitus type 2 without retinopathy.

Methods Prospective study of 49 patients with diabetes type 2. Twenty‐one men (42.9%) and twenty‐eight women (57.1%) were included. One eye by each patient was ramdomly included in the study. All of them were underwent three macular 512x128 volume cube scans with the Spectralis OCT system and with the Stratus OCT. The average of all the scans was calculated. The macular values of the nine areas corresponding to the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol were compared between the two systems.

Results We found statistically significant differences in all macular measures between the two systems (p<0.001). The average of macular thickness measured with Spectralis OCT was approximately 266.84 µm (± 12.22). The average of macular thickness using Stratus OCT was 194.56 µm (± 12.04). The difference of foveal values between both devices was approximately 72.28 µm (± 9.67). Retinal thickness values were higher with Spectralis OCT

Conclusion Macular measurements using Spectralis OCT are higher than those measured with Stratus OCT in patients with diabetes mellitus type 2. The results are comparable with the results obtained between Stratus OCT and Cirrus‐HD OCT in the same conditions and with the same sample of patients and with the values obtained in healthy subjects.
Keratoprosthesis surgery: Eastern European and Russian devices
Authors: ZAGORSKI ZF , YAKIMIENKO S , MOROZ ZI
Published: September 2009

Purpose To present the development and current status of keratoprosthesis surgery in Eastern Europe.

Methods Collection of data from coauthors and other surgeons involved in k‐pro surgery.

Results Large numbers of surgeries were performed in Filatov's Institute in Odessa (Ukraine), where over 1000 different types of devices developed by Puchkovskaya, Yakimienko and Golubenko were imlanted since 1966. The last model, s.c. "universal separable device" was implanted in over 750 with the best results (extrusion occured in about 2.5% cases). K‐pro devices in Russia were mostly developed by S. Fyodorov Z. Moroz, V. Zuyev, ?. Krasnov, V. Volkov, R. Gundorova, N. Ushakov and V. Bedilo. Over 1500 surgeries sine 1969 resulted in the visual aquity improvement in 94% of cases. Haptics were made of titanium, stainless steel and also biocompatible materials (xenopericardium). In Poland about 100 surgeries were performed using mostly Russian and Ukrainian devices. The results were less favorable than in countries of origin. Small numbers were also implanted in other East European states.

Conclusion In former Soviet Union keratoprosthesis surgery was well developed in selected centers (Moscow, Odessa). Surgeons in these places have gained extraordinary experience performing hundredes of surgeries. The results presented by the authors were excellent, however they were less favorable in the hands of surgeons from other countries.
Glaucoma associated with KPros
Authors: HILLE K
Published: September 2009

Purpose Glaucoma is one of the most serious problems in Keratoprostheses. Already glaucoma is very frequent in patients with severe changes of the ocular surface requiring keratoprosthesis surgery. About 50% of those patients have pre‐existing secondary glaucoma. Preoperatively all efforts should be done to detect its presence very early on. In KPro detection of glaucoma with traditional aids is difficult. A rough estimation of the tension by digital palpation will be the only available method. All indirect clues such as the medical history of glaucoma, echographic signs of disc cupping and anterior synechiae and examination of the visual field should be considered.

Methods The incidence of postoperative secondary glaucoma vary among the different kinds of prostheses according to the surgery affecting the anterior segment and the long term anatomic results. In Osteo‐Odonto‐Keratoprostheses (OOKP) the most vision threatening complication is a primary or secondary glaucoma, due to the extended interventions required in the anterior segment. In Boston Keratoprostheses the risk seems to be somehow less.

Results As the absorption of topical anti‐glaucomatous medication will not reach the inner eye because of the anatomic barrier in KPro the only promising possibilities of treatment are systemic carbonic anhydrase inhibitors, different kinds of aqueous shunts and endo‐cyclo‐laserphotocoagulation.

Conclusion Glaucoma is still a mayor problem in KPro. PS: This lession will be presented at the KPro‐Meeting!!
Does imaging help with preventing extrusion?
Authors: GOMAA A , SIPKOVA Z , FRANCIS I , HEROLD J , THORP S , LIU C
Published: September 2009

Both clinical and radiological methods can be used for early detection of resorption in OOKP patients; this is influential in preventing serious complications such as extrusion and endophthalmitis. Radiologically, use of either multidetector computed tomography (MDCT) or electron beam tomography (EBT) is valuable in identifying laminar resorption. A novel approach was recently adopted in Sussex Eye Hospital, using volume rendering software in processing previously obtained MDCT images, to calculate volume of the OOKP lamina rather than 2D measurements. We present the results of an observational retrospective case series study to illustrate the use of this approach. We describe how it can be used to calculate percentage change in volume of the lamina over time and how this can be correlated with clinical laminar resorption. We will also discuss further recommendations to build upon this advance.
Comparison of the peripapillary retinal nerve fiber layer thickness in healthy subjects measured by spectral‐domain Cirrus optical coherence tomography and time‐domain Stratus optical coherence tomography
Authors: FUERTES I , PINILLA I , GARCIA MARTIN E , GIL ARRIBAS L , IDOIPE M , CALVO PEREZ P
Published: September 2009

Purpose to compare Cirrus Fourier‐domain optical coherence tomography (OCT) with Stratus Time‐domain OCT for measuring the peripapillary retinal nerve fiber layer (RNFL) thickness in healthy subjects.

Methods One hundred and thirty two healthy subjects were prospectively and consecutively selected. Only one eye was ramdomly included in the study. All of them underwent three optic disc cube 200x200 scans with the Cirrus HD‐OCT system (Carl Zeiss Meditec, Inc.). The average of the 3 scans was calculated. With the Stratus OCT system (Carl Zeiss Meditec, Inc.) a fast RNFL thickness scan was recorded. The average of RNFL thickness, and RNFL thickness at each quadrant, and each 12 clock‐hours position was evaluated comparing both devices. Reproducibility of RNFL thickness measurements using de Cirrus HD‐OCT was studied, and the variation coefficient (COV) was calculated.

Results Mean age was 40.06 ± 13.63 years (ranged from 17 to 72 years). Thirty nine were men (29.5%) and 93 women (70.5%). The average of the peripapillary RNFL thickness was 96.16 µm and 98.27 µm using Cirrus HD‐OCT and Stratus OCT respectively (p=0.001). Statistically differences were found in the temporal quadrant (p=0.026) as well as in several hour sectors. The Cirrus HD‐OCT reproducibility was high, with a mean COV of 4.54% (ranged from 1.64% to 6.37%).

Conclusion Mean peripapillary RNFL thickness measured with Cirrus HD‐OCT is slightly lower than with Stratus OCT.
Comparison of spectral‐domain Cirrus optical coherence tomography and time‐domain Stratus optical coherence tomography for the evaluation of macular thickness in healthy subjects
Authors: FUERTES I , PINILLA I , GARCIA MARTIN E , IDOIPE M , GIL ARRIBAS L
Published: September 2009

Purpose to compare Cirrus Fourier‐domain optical coherence tomograph (OCT) with Stratus Time‐domain OCT for acquiring retinal images and measuring retinal thickness.

Methods Eighty five eyes from 85 healthy subjects, 26 men (30.6%) and 59 women (69.4%), aged 16 to 72 years were prospective and consecutively selected. All of them underwent three macular 512x128 volume cube scans with the Cirrus HD‐OCT system (Carl Zeiss Meditec, Inc.). The average of these three scans was calculated. With the Stratus OCT system (Carl Zeiss Meditec, Inc.) a fast macular scan was recorded. The nine areas corresponding to the Early Treatment Diabetic Retinopathy Study (ETDRS) macular protocol were compared between both devices. The reproducibility of macular thickness measurements using de Cirrus HD‐OCT was studied, and the variation coefficient (COV) of each parameter was assessed.

Results Cirrus HD‐OCT macular thickness measurements were approximately 64.22 µm higher than those from Stratus OCT (266.40 µm vs 202.18 µm). The measurements in all nine ETDRS areas were statistically higher using the Cirrus HD‐OCT. Nasal inner area showed the highest value. Retinal thickness measurements using the 512x128 macular cube scan were highly reproducible for the nine ETDRS areas. Mean COV was 1.45 ± 1.11% (ranged from 0.98% to 2.49%). The lowest COV was found for the temporal inner ETDRS area (COV=0.98%) and the highest for the central ETDRS area (COV=2.49%).

Conclusion Macular measurements using Cirrus HD‐OCT are clearly higher than those obtained by Stratus OCT.
Emerging and poorly known viral inflammatory eye diseases
Authors: KHAIRALLAH M
Published: September 2009

Arthropod vector borne diseases are among the most important emergent infections. They include a wide variety of bacterial, viral, and parasitic diseases that are transmitted to humans by the bite of mosquito, tick, or other arthropod. Most of them are prevalent in tropical and subtropical areas, but they tend to spread into new regions mainly due to increasing temperatures worldwide, movement of people, increasing human population densities, wider dispersal of competent vectors, and transportation of goods and animals. Numerous arthropod vector borne diseases have been associated with uveitis. Among them, specific viral diseases recently emerged as important causes of uveitis in the developing and developed world. They include West Nile virus (WNV) infection, Rift Valley fever (RVF) , dengue fever (DF), and Chikungunya. These viral diseases have been recently associated with an array of ocular manifestations, including anterior uveitis, retinitis, chorioretinitis, retinal vaculitis, and optic nerve involvement. Proper clinical diagnosis of any of these infectious diseases is based on epidemiological data, history, systemic symptoms and signs, and the pattern of uveitis. The diagnosis is usually confirmed by detection of specific antibody in serum. A systematic ocular examination, showing fairly typical findings, can help establish an early clinical diagnosis of a specific systemic viral infection while serologic testing is pending. Prevention remains the mainstay for control of arthropod vector borne viral diseases.
Appraisal and management of subclinical choroidal inflammation: the iceberg phenomenon
Authors: HERBORT CP
Published: September 2009

Purpose To explore further the ocular fundal structures after funduscopy has been performed in intraocular inflammatory diseases, we have at our disposal among other investigational imaging methods, fluorescence angiography comprising fluorescein angiography (FA) and indocyanine green angiography (ICGA). In most cases dual FA & ICGA is necessary as the two methods image completely different structures. Fluorescein angiography is giving information on superficial structures including the optic disc, the retinal vessels and the retina as well as on the RPE, whereas ICGA is exploring the choroidal compartment. In contrast to FA that usually does not furnish additional information but is only giving more precise images of the superficial structures explored, ICGA is revealing elements, in case of choroidal inflammatory involvement, that no other method can show. The choroidal inflammatory lesions can be very extensive while often causing only faint or no signs during clinical examination and with other investigational imaging methods, a phenomenon which corresponds to the so‐called “iceberg effect”. This aptitude of ICGA to show lesions that are otherwise inaccessible make it an essential method to detect and follow choroidal lesions.

Methods Cases where diagnosis cannot be made without ICGA or cases where inflammation can only be followeb by ICGA, the so‐called iceberg constellation because other methods show only faint or no signs, will be presented.

Conclusion Inflammatory lesions limited to the choroid cannot be detected without performing ICGA which is indispensible to diagnose purely choroidal diseae and to monitor the evolution of choroidal inflammation.
Use of the contrast sensibility in the diagnosis of diabetic retinopathy and diabetic macular edema
Authors: IBANEZ J , VALYI Z , PEREZ GARCIA D , PEIRO C , CRISTOBAL JA , FAURE E , SAINZ A
Published: September 2009

Purpose To determine the validity of the contrast sensibility, in the diagnosis of the diabetic retinopathy and macular diabetic edema.

Methods Cross ‐sectional observational study consisting of 628 eyes of patients with diabetic retinopathy, being realized the curve of contrast sensibility using the test CSV‐1000E. There were studied 4 spatial frequencies (3,6,12,16 cycles / second). The results were analyzed for each of the frequencies, corrected by the age, degree of diabetic retinopathy and thickness macular.

Results In patients with retinopatía diabetic sensibilities of 4 were obtained (3 ciclos/seg) 2 (6 ciclos/seg) and 1,5 (12 and 18 ciclos/seg) .La average decrease of the curve corrected by the age was 30 %, 37 %, 42 % and 45 % for each of the analyzed frequencies. The patients with thicknesses macular top to 400 microns experimented decreases superior to 50 % of the curve of sensibility.

Conclusion We find a widespread reduction of the curve of sensibility to the contrast, in patients with diabetic retinopathy and diabetic macular edema. The high frequencies were more prematurely affected, being able to serve in proof of screening, since the functional damage in these frequencies might precede the structural anomaly.
Use of retinal photography in the diagnosis of clinically significant macular edema (CSME)
Authors: IBANEZ J , PEREZ GARCIA D , VALYI Z , MATEO OROBIA AJ , CRISTOBAL JA , FAURE E , SAINZ A
Published: September 2009

Purpose To determine the validity of the simple and stereoscopic retinal photography in the diagnosis of clinically significant macular edema (CSME).

Methods Cross‐sectional observational study consisting of 420 eyes of patients with diabetic retinopathy, which was a combination of retinography (simple, light and stereoscopic aneritra), after expansion, to determine its validity in the diagnosis of diabetic macular edema. We calculated sensitivity, specificity, positive and negative predictive values and the correlation with the gold standard test (optical coherence tomography). The retinographs were evaluated by three experts and their results analyzed by the statistical program SPSS 15.0 Windows.

Results For the analysis of the clinically significant macular edema( CSME), there were obtained sensibilities near to 80 % (color photographs 45 º, green 45 º, 30 º) and superior to 80 % (stereoscopic green 45 º, stereoscopic color 30 º, stereoscopic green to 30 º), reached the stereoscopic green photography 30 º, a sensibility of 92,5 %. The specificity was 90%. The positive predictive value was greater than 95% and the negative value greater than 90% with a coefficient of agreement (80%) and a degree of consistency with the benchmark of over 80%. Less than 5% of the retinographs were of poor quality.

Conclusion The stereoscopic retinal photography to color of 45 º and 30 º, aneritra of 30 º and stereoscopic aneritra of 30 º offer a sufficient sensibility and specificity to be used in the diagnosis of clinically significant macular edema (CSME).
Efficacy after intravitreal bevacizumab and triamcinolone injection in BRVO patients
Authors: CHOI M , LEW Y
Published: September 2009

Purpose To compare the efficacy of the injection after intravitreal bevacizumab and Triancinolone(TA) in patients with macular edema secondary to BRVO

Methods A consecutive retrospective review of patients with ME secondary to BRVO who were treated with intravitreal bevacizumab(1.25mg/0.05mL) and TA(4 mg/ml). Patients underwent complete ophthalmic evaluation, which included visual acuity testing(log MAR), OCT, and/or angiographic testing.

Results There were 53 patients who received intravitreal bevacizumab(21 eyes) and TA(32 eyes) injections. The mean length of follow‐up was 13.2 months. In patients with intravitreal bevacizumab injection, the mean visual acuity(VA) improved from 0.77±0.50 at baseline to 0.43±0.30(p=0.095) at 1 month, 0.31±0.22(p=0.007) at 3 months and 0.51±0.26(p=0.299) at last follow‐up. The mean central macular thickness(CMT) was 616.0±77.0µm at baseline and decreased to 259.0±32.0µm(p=0.028), 267±62.4µm(p=0.029)and 323.3±34.3µm(p=0.036) at 1,3 months, and last follow‐up. In patients with intravitreal TA injection, the mean VA improved from 0.78±0.36 at baseline to 0.54±0.26(p<0.001) at 1 month, 0.43±0.28(p=0.450) at 3 months and 0.63±0.36(p=0.001) at last follow‐up. The mean CMT was 577.5 ±29.8µm at baseline and decreased to 397.2±114.5µm(p=0.004), 391±72.4 µm(p=0.003)and 412.3±123.1µm(p=0.034) at 1, 3 months, and last follow‐up. No adverse side effects were observed following injections.

Conclusion The observed anatomic and VA improvements and lack of serious adverse side effects after intravitreal bevacizumab and TA injection in ME. However, patients received intravitreal bevacizumab injection led to no significant difference in visual acuity and macular thickness compared to the group treated with Triamcinolone injection.
Internal limiting membrane surrounding idiopathic stage 4 macular hole contains bundles of actin microfilaments
Authors: MENDRINOS E , TSILIMBARIS M , TSOKA P , BOCHATON‐PIALLAT ML , GILODI N , POURNARAS CJ
Published: September 2009

Purpose To study internal limiting membrane (ILM) specimens obtained from a case of stage 4 macular hole surgery with confocal microscopy and investigate the presence of actin microfilaments.

Methods A 68 year‐old woman underwent 20‐gauge transconjunctival sutureless vitrectomy for stage 4 idiopathic macular hole. Triamcinolone –acetonide was used for visualizing the vitreous hyaloid. Following vitrectomy, the ILM was stained with Brilliant blue dye, then peeled off using an intraocular forceps. Two separate ILM specimens were obtained during surgery; the first around the macular hole and the second one disc diameter away from the macular hole up to the temporal vascular arcades and the optic disk. At the end of the surgery, air‐gas (C3F8 16%) exchange was performed. The ILM specimens were studied immunohistochemically using confocal microscopy after labeling with antibodies to actin and fibronectin.

Results The ILM specimen around the macular hole was stained positive for both fibronectin and actin, whereas the ILM specimen away from the macular hole was stained positive only for fibronectin. Preoperative evaluation of the macular hole biomicroscopically and imaging with optical coherence tomography showed absence of any epiretinal membrane (ERM).

Conclusion ILM surrounding stage 4 macular hole contains bundles of actin microfilaments, suggesting the presence of cells with contractile properties even in the absence of associated ERM. These findings suggest that tangential traction may contribute to the pathogenesis of late stage macular hole development and/or enlargement and support removal of ILM in late stage macular hole surgery.
Long‐term visual prognosis in necrotising herpetic retinitis
Authors: COSTANTINI E , DUCOS DE LAHITTE G , TRAN T , CASSOUX N , FARDEAU C , TERRADA C , AKNIN C , ROZENBERG F , LEHOANG P , BODAGHI B
Published: September 2009

Purpose To determine the long‐term ocular complications and visual outcome in patients with necrotising herpetic retinitis (NHR).

Methods 26 patients (33 eyes) with NRH diagnosed between June 1987 and January 2002 at Pitie‐Salpetriere Hospital, in Paris, France, were retrospectively reviewed. Demographic data, clinical presentation, viral identification (when possible), initial therapeutic management, long‐term antiviral therapy, complications and final visual acuity were analyzed.

Results 16 patients (61.5%) were male, 10 (38.5%) were female. Age ranged from 11 to 67 years (mean 40.6 years). All patients were treated with intensive intravenous antiviral therapy, 9 (34.6%) with additional intravitreous ganciclovir injections. At last examination, 20 patients (76.9%) were still under prophylactic antiviral treatment. Complications were cataract (63.6%), retinal detachment (48.5%), recurrence (33.3%), macular edema (36.4%), optic atrophy (30.3%) and epimacular membrane (27.3%). Final visual acuity was below 20/200 in 15 eyes (45.5%). The minimal follow‐up was 3 years.

Conclusion Despite aggressive antiviral therapy, visual prognosis remains guarded in patients with NHR. Retinal vasculopathy and optic disc alterations are major factors to consider in order to improve the visual outcome.
Vitreous haemorrhage and retinal vasculitis as manifestations of cat‐scratch disease
Authors: DORE S , CONTINI E , CARTA F , PINNA A
Published: September 2009

Purpose To report a rare case of vitreous haemorrhage and retinal vasculitis secondary to cat scratch disease, caused by Bartonella henselae.

Methods A 42‐year‐old apparently healthy farmer presented with a 5‐day history of blurred vision in his right eye. Right visual acuity was 20/25. Slit‐lamp examination of the right eye revealed mild vitreous haemorrhage and diffuse retinal haemorrhages in the middle‐peripheral retina. The left eye was unremarkable. Fluorescein angiography showed signs of retinal vasculitis in the right eye. The patient owned several cats, but had no history of cat bites or scratches.

Results A blood sample taken on the day of admission revealed the presence of IgM (titre=1:40) and IgG (titre=1:80) to B. henselae. Accordingly, the diagnosis of cat‐scratch disease was made. The retinal vasculitis resolved after 8 days of therapy with oral azithromycin.

Conclusion Apart from neuroretinitis, the ocular complication associated with cat‐scratch disease may include vitreous haemorrhage and retinal vasculitis.
Acute Effect of Pimobendan and Furosemide on the Circulating Renin‐Angiotensin‐Aldosterone System in Healthy Dogs
Authors: Sayer M.B. , Atkins C.E. , Fujii Y. , Adams A.K. , DeFrancesco T.C. , Keene B.W.
Published: September 2009

Background:The renin‐angiotensin‐aldosterone system (RAAS) is activated in states of decreased cardiac output and by certain cardiovascular therapeutic agents, such as loop diuretics and vasodilators.

Hypothesis:Short‐term treatment with the inodilator, pimobendan, will not activate the circulating RAAS because its vasodilatory action will be offset by its positive inotropic property, thereby ameliorating RAAS stimulation at the juxtaglomerular apparatus. Furthermore, pimobendan will suppress RAAS activation produced by furosemide.

Animals:Nine healthy laboratory dogs were used in this study.

Methods:Experimental, cross‐over study. Dogs were administered pimobendan (0.5 mg/kg q12h) for 4 days followed by furosemide (2 mg/kg q12h) and then, after a wash‐out period, a combination of the drugs. Aldosterone : creatinine (A : Cr) was measured at the end of each treatment cycle.

Results:There was no significant increase in the average urinary A : Cr with the administration of pimobendan (control urinary A : Cr = 0.46, standard deviation (SD) 0.33; pimobendan A : Cr = 0.48, SD 0.28). There was a significant increase in the average urinary A : Cr after administration of furosemide (urinary A : Cr = 1.3, SD 0.70) and with the combination of furosemide and pimobendan (urinary A : Cr = 2.9, SD 1.6).

Conclusions and Clinical Relevance:Short‐term administration of high‐dose pimobendan, does not activate the RAAS in healthy dogs. Pimobendan did not prevent RAAS activation associated with furosemide therapy. These results in healthy dogs suggest that furosemide therapy, with or without pimobendan, should be accompanied by RAAS suppressive therapy.
Effect of Fuel Injection Timing and Injection Pressure on Combustion and Odorous Emissions in DI Diesel Engines
Authors: Roy Murari Mohon
Published: September 2009

This study investigated the effect of fuel injection timing and injection pressure on combustion and odorous emissions in a direct injection diesel engine. Injection timings from 15 deg before top dead center (BTDC) to top dead center (TDC) and injection pressures from 20 MPa to 120 MPa were tested. In emissions, exhaust odor, irritation, aldehydes, total hydrocarbon, and hydrocarbon components are compared in different injection timings and injection pressures condition. Injection timings where main combustion takes place very close to TDC are found to show minimum odorous emissions. Moderate injection pressures (60–80 MPa) showed lower emissions including odor and irritation due to proper mixture formation. Below the injection pressure of 40 MPa, and over 80 MPa, emissions become worse. Combustion analysis is performed by taking cylinder pressures after engine warm-up for different injection timings and injection pressures and analyzing cylinder temperatures and heat release rates. Cylinder pressures and temperatures are gradually decreased when injection timings are retarded. Ignition delay becomes shortest at 5–10 deg BTDC injection timings. The peak cylinder pressure and temperature are increased with higher injection pressures. The shortest ignition delay and minimum emissions is found at around 60 MPa of injection pressure.
Energy Conservation Opportunity in Boiler Systems
Authors: Kaya Durmus , Eyidogan Muharrem
Published: September 2009

In this study, “energy efficiency” study has been performed for a natural gas fuelled boiler, operating at 42,000 kPa pressure and 713.15 K temperature, with a nominal capacity of 33.33 kg/s steam. Within this frame, temperature, pressure, velocity, and gas analysis measurements have been made, and energy, mass balances, and exergy analysis have been formed. Then, the efficiency of boiler, potential energy saving options and savings quantities, investment costs, and payback period for normal operating conditions have been calculated from the energy and mass balances. Implementation cost is required only for reducing air leakages in the rotary type air heater and surface thermal losses. The investment cost for reducing air leakage in the rotary type air heater to the acceptable limits (10%) is 600,000 USD. Under these circumstances, the payback period of this investment cost is about fifteen months.
Risk Perspectives on Rail Transport of Spent Nuclear Fuel
Authors: Bajwa Christopher S. , Easton Earl P.
Published: September 2009

The US Nuclear Regulatory Commission (NRC) has completed a study of historical rail accidents (from 1975 to 2005) involving hazardous materials and long duration fires in the United States. The study was initiated to determine what types of accidents had actually occurred, and what type of impact those types of accidents could have on the rail transport of spent nuclear fuel. The NRC found that almost 21 billion miles of rail shipments has yielded only a small number of accidents involving hazardous materials, eight of which involved both hazardous materials and long duration fires. The NRC reviewed these eight accidents in detail to determine what types of effects these accidents might have on a spent fuel cask, should one have been involved. The staff determined that the fires witnessed in the accidents studied would not have provided a fully engulfing fire environment as described by the hypothetical accident condition fire in NRC regulations for radioactive material transport found in Title 10 of the Code of Federal Regulations, Part 71, Section 73. This paper will detail the NRC study of these accidents and conclusions regarding effects on transportation casks exposed to the fires that resulted from these accidents.
Quorum-Quenching Acylase Reduces the Virulence of
Pseudomonas aeruginosa
in a
Caenorhabditis elegans
Infection Model
Authors: Papaioannou Evelina , Wahjudi Mariana , Nadal-Jimenez Pol , Koch Gudrun , Setroikromo Rita , Quax Wim J.
Published: September 2009

The
Pseudomonas aeruginosa
PAO1 gene
pvdQ
encodes an acyl-homoserine lactone (AHL) acylase capable of degrading
N
-(3-oxododecanoyl)-
l
-homoserine lactone by cleaving the AHL amide. PvdQ has been proven to function as a quorum quencher in vitro in a number of phenotypic assays. To address the question of whether PvdQ also shows quorum-quenching properties in vivo, an infection model based on the nematode
Caenorhabditis elegans
was explored. In a fast-acting paralysis assay, strain PAO1(pME
pvdQ
), which overproduces PvdQ, was shown to be less virulent than the wild-type strain. More than 75% of the nematodes exposed to PAO1(pME
pvdQ
) survived and continued to grow when using this strain as a food source. Interestingly, in a slow-killing assay monitoring the survival of the nematodes throughout a 4-day course, strain PAO1-Δ
pvdQ
was shown to be more virulent than the wild-type strain, confirming the role of PvdQ as a virulence-reducing agent. It was observed that larval stage 1 (L1) to L3-stage larvae benefit much more from protection by PvdQ than L4 worms. Finally, purified PvdQ protein was added to
C. elegans
worms infected with wild-type PAO1, and this resulted in reduced pathogenicity and increased the life span of the nematodes. From our observations we can conclude that PvdQ might be a strong candidate for antibacterial therapy against
Pseudomonas
infections.
Induction of Multidrug Resistance Mechanism inEscherichia coliBiofilms by Interplay between Tetracycline and Ampicillin Resistance Genes
Authors: May Thithiwat , Ito Akinobu , Okabe Satoshi
Published: September 2009

Biofilms gain resistance to various antimicrobial agents, and the presence of antibiotic resistance genes is thought to contribute to a biofilm-mediated antibiotic resistance. Here we showed the interplay between the tetracycline resistance efflux pump TetA(C) and the ampicillin resistance gene (blaTEM-1) in biofilms ofEscherichia coliharboring pBR322 in the presence of the mixture of ampicillin and tetracycline.E. coliin the biofilms could obtain the high-level resistance to ampicillin, tetracycline, penicillin, erythromycin, and chloramphenicol during biofilm development and maturation as a result of the interplay between the marker genes on the plasmids, the increase of plasmid copy number, and consequently the induction of the efflux systems on the bacterial chromosome, especially the EmrY/K and EvgA/S pumps. In addition, we characterized the overexpression of the TetA(C) pump that contributed to osmotic stress response and was involved in the induction of capsular colanic acid production, promoting formation of mature biofilms. However, this investigated phenomenon was highly dependent on the addition of the subinhibitory concentrations of antibiotic mixture, and the biofilm resistance behavior was limited to aminoglycoside antibiotics. Thus, marker genes on plasmids played an important role in both resistance of biofilm cells to antibiotics and in formation of mature biofilms, as they could trigger specific chromosomal resistance mechanisms to confer a high-level resistance during biofilm formation.
Beijing Genotype of
Mycobacterium tuberculosis
Is Significantly Associated with High-Level Fluoroquinolone Resistance in Vietnam
Authors: An Duong Duy , Hong Duyen Nguyen Thi , Lan Nguyen Thi Ngoc , Hoa Dai Viet , Ha Dang Thi Minh , Kiet Vo Sy , Thu Do Dang Anh , Van Vinh Chau Nguyen , Dung Nguyen Huy , Sy Dinh Ngoc , Farrar Jeremy , Caws Maxine
Published: September 2009

Consecutive fluoroquinolone (FQ)-resistant isolates (
n
= 109) identified at the Pham Ngoc Thach Hospital for Tuberculosis, Ho Chi Minh City, Vietnam, were sequenced in the quinolone resistance-determining regions of the
gyrA
and
gyrB
genes and typed by large sequence polymorphism typing and spoligotyping to identify the Beijing genotype of
Mycobacterium tuberculosis
. Beijing genotype prevalence was compared with 109 consecutive isolates from newly presenting patients with pulmonary tuberculosis from the hospital outpatient department. Overall, 82.6% (
n
= 90/109) of isolates had mutations in
gyrAB
. Nine novel mutations were identified in
gyrB
(S486F, N538T, T539P, D500A, D500H, D500N, G509A, E540V, and E540D). The influence of these novel
gyrB
mutations on FQ resistance is not proven. The Beijing genotype was significantly associated with FQ resistance (odds ratio [OR], 2.39 [95% confidence interval {CI}, 1.34 to 4.25];
P
= 0.003). Furthermore, Beijing genotype FQ-resistant isolates were significantly more likely than FQ-resistant isolates of other genotypes to have
gyrA
mutations (OR, 7.75 [95% CI, 2.84 to 21.15];
P
= 0.0001) and high-level (>8 μg/ml) FQ resistance (OR, 11.0 [95% CI, 2.6 to 47.0];
P
= 0.001). The underlying mechanism of the association of the Beijing genotype with high-level FQ resistance in this setting remains to be determined. The association of the Beijing genotype with relatively high-level FQ resistance conferred by specific
gyrA
mutations reported here is of grave concern given the epidemic spread of the Beijing genotype and the current hopes for shorter first-line treatment regimens based on FQs.
Nonpolymorphic Human Immunodeficiency Virus Type 1 Protease and Reverse Transcriptase Treatment-Selected Mutations
Authors: Shahriar Rajin , Rhee Soo-Yon , Liu Tommy F. , Fessel W. Jeffrey , Scarsella Anthony , Towner William , Holmes Susan P. , Zolopa Andrew R. , Shafer Robert W.
Published: September 2009

The spectrum of human immunodeficiency virus type 1 (HIV-1) protease and reverse transcriptase (RT) mutations selected by antiretroviral (ARV) drugs requires ongoing reassessment as ARV treatment patterns evolve and increasing numbers of protease and RT sequences of different viral subtypes are published. Accordingly, we compared the prevalences of protease and RT mutations in HIV-1 group M sequences from individuals with and without a history of previous treatment with protease inhibitors (PIs) or RT inhibitors (RTIs). Mutations in protease sequences from 26,888 individuals and in RT sequences from 25,695 individuals were classified according to whether they were nonpolymorphic in untreated individuals and whether their prevalence increased fivefold with ARV therapy. This analysis showed that 88 PI-selected and 122 RTI-selected nonpolymorphic mutations had a prevalence that was fivefold higher in individuals receiving ARVs than in ARV-naïve individuals. This was an increase of 47% and 77%, respectively, compared with the 60 PI- and 69 RTI-selected mutations identified in a similar analysis that we published in 2005 using subtype B sequences obtained from one-fourth as many individuals. In conclusion, many nonpolymorphic mutations in protease and RT are under ARV selection pressure. The spectrum of treatment-selected mutations is changing as data for more individuals are collected, treatment exposures change, and the number of available sequences from non-subtype B viruses increases.
The Phthalocyanine Prototype Derivative Alcian Blue Is the First Synthetic Agent with Selective Anti-Human Immunodeficiency Virus Activity Due to Its gp120 Glycan-Binding Potential
Authors: François Katrien O. , Pannecouque Christophe , Auwerx Joeri , Lozano Virginia , Pérez-Pérez Maria-Jésus , Schols Dominique , Balzarini Jan
Published: September 2009

Alcian Blue (AB), a phthalocyanine derivative, is able to prevent infection by a wide spectrum of human immunodeficiency virus type 1 (HIV-1), HIV-2, and simian immunodeficiency virus strains in various cell types [T cells, (co)receptor-transfected cells, and peripheral blood mononuclear cells]. With the exception of herpes simplex virus, AB is inactive against a broad variety of other (DNA and RNA) viruses. Time-of-addition studies show that AB prevents HIV-1 infection at the virus entry stage, exactly at the same time as carbohydrate-binding agents do. AB also efficiently prevents fusion between persistently HIV-1-infected HUT-78 cells and uninfected (CD4
+
) lymphocytes, DC-SIGN-directed HIV-1 capture, and subsequent transmission to uninfected (CD4
+
) T lymphocytes. Prolonged passaging of HIV-1 at dose-escalating concentrations of AB resulted in the selection of mutant virus strains in which several N-glycans of the HIV-1 gp120 envelope were deleted and in which positively charged amino acid mutations in both gp120 and gp41 appeared. A mutant virus strain in which four N-glycans were deleted showed a 10-fold decrease in sensitivity to the inhibitory effect of AB. These data suggest that AB is likely endowed with carbohydrate-binding properties and can be considered an important lead compound in the development of novel synthetic nonpeptidic antiviral drugs targeting the glycans of the envelope of HIV.
Diversity, Epidemiology, and Genetics of Class D β-Lactamases
Authors: Poirel Laurent , Naas Thierry , Nordmann Patrice
Published: September 2009

Class D β-lactamase-mediated resistance to β-lactams has been increasingly reported during the last decade. Those enzymes also known as oxacillinases or OXAs are widely distributed among Gram negatives. Genes encoding class D β-lactamases are known to be intrinsic in many Gram-negative rods, includingAcinetobacter baumanniiandPseudomonas aeruginosa, but play a minor role in natural resistance phenotypes. The OXAs (ca. 150 variants reported so far) are characterized by an important genetic diversity and a great heterogeneity in terms of β-lactam hydrolysis spectrum. The acquired OXAs possess either a narrow spectrum or an expanded spectrum of hydrolysis, including carbapenems in several instances. Acquired class D β-lactamase genes are mostly associated to class 1 integron or to insertion sequences.
Nonclinical Pharmacokinetics of Oseltamivir and Oseltamivir Carboxylate in the Central Nervous System
Authors: Hoffmann Gerhard , Funk Christoph , Fowler Stephen , Otteneder Michael B. , Breidenbach Alexander , Rayner Craig R. , Chu Tom , Prinssen Eric P.
Published: September 2009

Oseltamivir, a potent and selective inhibitor of influenza A and B virus neuraminidases, is a prodrug that is systemically converted into the active metabolite oseltamivir carboxylate. In light of reported neuropsychiatric events in influenza patients, including some taking oseltamivir, and as part of a full assessment to determine whether oseltamivir could contribute to, or exacerbate, such events, we undertook a series of nonclinical studies. In particular, we investigated (i) the distribution of oseltamivir and oseltamivir carboxylate in the central nervous system of rats after single intravenous doses of oseltamivir and oseltamivir carboxylate and oral doses of oseltamivir, (ii) the active transport of oseltamivir and oseltamivir carboxylate in vitro by transporters located in the blood-brain barrier, and (iii) the extent of local conversion of oseltamivir to oseltamivir carboxylate in brain fractions. In all experiments, results showed that the extent of partitioning of oseltamivir and especially oseltamivir carboxylate to the central nervous system was low. Brain-to-plasma exposure ratios were approximately 0.2 for oseltamivir and 0.01 for oseltamivir carboxylate. Apart from oseltamivir being a good substrate for the P-glycoprotein transporter, no other active transport processes were observed. The conversion of the prodrug to the active metabolite was slow and limited in human and rat brain S9 fractions. Overall, these studies indicate that the potential for oseltamivir and oseltamivir carboxylate to reach the central nervous system in high quantities is low and, together with other analyses and studies, that their involvement in neuropsychiatric events in influenza patients is unlikely.
Opa+and Opa−Isolates ofNeisseria meningitidisandNeisseria gonorrhoeaeInduce Sustained Proliferative Responses in Human CD4+T Cells
Authors: Youssef Abdel-Rahman , van der Flier Michiel , Estevão Silvia , Hartwig Nico G. , van der Ley Peter , Virji Mumtaz
Published: September 2009

T cells may interact with a number of bacterial surface antigens, an encounter which has the potential to downmodulate host immune responses.Neisseria meningitidis, a human colonizer and an agent of septicemia and meningitis, expresses Opa proteins which interact with the CEACAM1 receptor expressed on activated T cells. Since CEACAM1 can act as an inhibitory receptor and T cells in subepithelial tissues may encounter whole bacteria, which often express Opa proteins in vivo, this study assessed primarily if Opa proteins expressed on meningococci affect T-cell functions. In addition, Opa-containing outer membrane vesicles (OMV) have been used as vaccine antigens, and therefore Opa+and Opa−OMV were also studied. While Opa+bacteria adhered to CEACAM-expressing T cells, both the Opa+and Opa−phenotypes induced no to a small transient depression, followed by a prolonged increase in proliferation as well as cytokine production. Such responses were also observed with heat-killed bacteria or OMV. In addition, while anti-CEACAM antibodies alone inhibited proliferation, on coincubation of T cells with bacteria and the antibodies, bacterial effects predominated and were Opa independent. Thus, while Opa proteins ofN. meningitidiscan bind to T-cell-expressed CEACAM1, this is not sufficient to overcome the T-cell recognition of bacterial factors, which results in a proliferative and cytokine response, an observation consistent with the ability of the host to establish lasting immunity to Opa-expressing meningococci that it frequently encounters. The data also imply that Opa-proficient vaccine preparations may not necessarily inhibit T-cell functions via CEACAM1 binding.
Genetic Structure and Distribution of the Colibactin Genomic Island among Members of the Family
Enterobacteriaceae
Authors: Putze Johannes , Hennequin Claire , Nougayrède Jean-Philippe , Zhang Wenlan , Homburg Stefan , Karch Helge , Bringer Marie-Agnés , Fayolle Corinne , Carniel Elisabeth , Rabsch Wolfgang , Oelschlaeger Tobias A. , Oswald Eric , Forestier Christiane , Hacker Jörg , Dobrindt Ulrich
Published: September 2009

A genomic island encoding the biosynthesis and secretion pathway of putative hybrid nonribosomal peptide-polyketide colibactin has been recently described in
Escherichia coli
. Colibactin acts as a cyclomodulin and blocks the eukaryotic cell cycle. The origin and prevalence of the colibactin island among enterobacteria are unknown. We therefore screened 1,565 isolates of different genera and species related to the
Enterobacteriaceae
by PCR for the presence of this DNA element. The island was detected not only in
E. coli
but also in
Klebsiella pneumoniae
,
Enterobacter aerogenes
, and
Citrobacter koseri
isolates. It was highly conserved among these species and was always associated with the yersiniabactin determinant. Structural variations between individual strains were only observed in an intergenic region containing variable numbers of tandem repeats. In
E. coli
, the colibactin island was usually restricted to isolates of phylogenetic group B2 and inserted at the
asnW
tRNA locus. Interestingly, in
K. pneumoniae
,
E. aerogenes
,
C. koseri
, and three
E. coli
strains of phylogenetic group B1, the functional colibactin determinant was associated with a genetic element similar to the integrative and conjugative elements ICE
Ec1
and ICE
Kp1
and to several enterobacterial plasmids. Different
asn
tRNA genes served as chromosomal insertion sites of the ICE-associated colibactin determinant:
asnU
in the three
E. coli
strains of ECOR group B1, and different
asn
tRNA loci in
K. pneumoniae
. The detection of the colibactin genes associated with an ICE-like element in several enterobacteria provides new insights into the spread of this gene cluster and its putative mode of transfer. Our results shed light on the mechanisms of genetic exchange between members of the family
Enterobacteriaceae
.