Compatibility of fosfomycin with different commercial peritoneal dialysis solutions.

For treatment of peritoneal dialysis-related peritonitis, intraperitoneal administration of antibiotics remains the preferable route. For home-based therapy, patients are commonly supplied with peritoneal dialysis fluids already containing antimicrobial agents. The present study set out to investigate the compatibility of fosfomycin with different peritoneal dialysis fluids, namely, Extraneal®, Nutrineal®, Physioneal® 1.36% and Physioneal® 2.27%, under varying storage conditions. The peritoneal dialysis fluid bags including 4 g fosfomycin were stored over 14 days at refrigeration temperature (6°C) and room temperature (25°C) and over 24 h at body temperature (37°C). Drug concentrations over time were determined by using high-performance liquid chromatography coupled to a mass spectrometer. In addition, drug activity was assessed by a disk diffusion method, diluent stability by visual inspection and drug adsorption by comparison of the measured and calculated concentrations. Blank peritoneal dialysis fluids and deionized water were used as comparator solutions. Fosfomycin was stable in all peritoneal dialysis fluids and at each storage condition investigated over the whole study period. The remaining drug concentrations ranged between 94% and 104% of the respective initial concentrations. No significant drug adsorption was observed for any peritoneal dialysis fluid at any storage condition. No relevant reduction of antimicrobial activity was observed. Fosfomycin is compatible with Extraneal®, Nutrineal® and Physioneal® for up to two weeks at refrigeration or room temperature and may be used for home-based therapy. No dose adjustment is needed due to adsorption or degradation.

The influence of different peritoneal dialysis fluids on the in vitro activity of ampicillin, daptomycin, and linezolid against Enterococcus faecalis.

Intraperitoneal administration of antibiotics is recommended for the treatment of peritoneal dialysis-related peritonitis. However, little data are available on a possible interference between peritoneal dialysis fluids and the activity of antimicrobial agents. Thus, the present in vitro study set out to investigate the influence of different peritoneal dialysis fluids on the antimicrobial activity of ampicillin, linezolid, and daptomycin against Enterococcus faecalis. Time-kill curves in four different peritoneal dialysis fluids were performed over 24 h with four different concentrations (1 × MIC, 4 × MIC, 8 × MIC, 30 × MIC) of each antibiotic evaluated. Cation-adjusted Mueller-Hinton broth was used as the comparator solution. All four peritoneal dialysis fluids evaluated had a bacteriostatic effect on the growth of Enterococcus faecalis. Compared to the cation-adjusted Mueller-Hinton broth comparator solution, the antimicrobial activity of all antibiotics tested was reduced. For ampicillin and linezolid, no activity was found in any peritoneal dialysis fluid, regardless of the concentration. Daptomycin demonstrated dose-dependent activity in all peritoneal dialysis fluids. Bactericidal activity was observed at the highest concentrations evaluated in Dianeal® PDG4 and Extraneal®, but not in concentrations lower than 30 × MIC and not in Nutrineal® PD4 and Physioneal® 40. The antimicrobial activity of ampicillin and linezolid is limited in peritoneal dialysis fluids in vitro. Daptomycin is highly effective in peritoneal dialysis fluids and might, thus, serve as an important treatment option in peritoneal dialysis-related peritonitis. Further studies are needed to evaluate the clinical impact of the present findings.

Calculating radiotherapy margins based on Bayesian modelling of patient specific random errors.

Collected real-life clinical target volume (CTV) displacement data show that some patients undergoing external beam radiotherapy (EBRT) demonstrate significantly more fraction-to-fraction variability in their displacement ('random error') than others. This contrasts with the common assumption made by historical recipes for margin estimation for EBRT, that the random error is constant across patients. In this work we present statistical models of CTV displacements in which random errors are characterised by an inverse gamma (IG) distribution in order to assess the impact of random error variability on CTV-to-PTV margin widths, for eight real world patient cohorts from four institutions, and for different sites of malignancy. We considered a variety of clinical treatment requirements and penumbral widths. The eight cohorts consisted of a total of 874 patients and 27 391 treatment sessions. Compared to a traditional margin recipe that assumes constant random errors across patients, for a typical 4 mm penumbral width, the IG based margin model mandates that in order to satisfy the common clinical requirement that 90% of patients receive at least 95% of prescribed RT dose to the entire CTV, margins be increased by a median of 10% (range over the eight cohorts -19% to +35%). This substantially reduces the proportion of patients for whom margins are too small to satisfy clinical requirements.

MR simulation for prostate radiation therapy: effect of coil mounting position on image quality.

OBJECTIVE: To eliminate the effects of body deformation for MR-based prostate treatment planning, coil mounts are essential. In this study, we evaluated the effect of the coil set-up on image quality. METHODS: A custom-designed pelvic-shaped phantom was scanned by systematically increasing the anterior body-to-coil (BTC) distance from 30 to 90 mm. The image quality near the organs of interest was determined in order to characterize the relationship between image quality and BTC distance at the critical organ structures. The half intensity reduction (HIR) was calculated to determine the sensitivity of each organ structure to the BTC distance change. RESULTS: As the BTC distance increased, the uniformity reduced at 3% per millimetre. The HIR value indicated that the bladder signal is most sensitive to the change in BTC distance. By maintaining a constant BTC distance set-up, the intensity uniformity was improved by 28% along the B0 directions. CONCLUSION: Positioning the MRI coil on mounts can reduce body deformation but adversely degrades the image quality. The magnitude of this effect has been quantified for prostate MR simulation scanning. The coil needs to be positioned not only with a minimal but also uniform BTC distance in order to maximize image quality. ADVANCES IN KNOWLEDGE: A method to characterize the effect on image quality due to the use of coil mounts was demonstrated. Coil mounts whose height can be adjusted individually to keep BTC distance constant are necessary to maintain a uniform image across the entire field of view.

Anomalous impurity segregation and local bonding fluctuation in l-Si.

Anomalous impurity redistribution after a laser irradiation process in group-IV elements has been reported in numerous papers. In this Letter, we correlate this still unexplained behavior with the peculiar bonding character of the liquid state of group-IV semiconductors. Analyzing the B-Si system in a wide range of experimental conditions we demonstrate that this phenomenon derives from the non-Fickian diffusion transport of B in l-Si. The proposed diffusion model relies on the balance between two impurity states in different bonding configurations: one migrating at higher diffusivity than the other. This microscopic mechanism explains the anomalous B segregation, whereas accurate comparisons between experimental chemical profiles and simulation results validate the model.

Limitations of 64-detector-row computed tomography coronary angiography: calcium and motion but not short experience.

BACKGROUND: Recently, 64-detector-row computed tomography coronary angiography (CTA) has been introduced for the noninvasive diagnosis of coronary artery disease. PURPOSE: To evaluate the diagnostic capacity and limitations of a newly established CTA service. MATERIAL AND METHODS: In 101 outpatients with suspected coronary artery disease, 64-detector-row CTA (VCT Lightspeed 64; GE Healthcare, Milwaukee, Wisc., USA) was performed before invasive coronary angiography (ICA). The presence of >50% diameter coronary stenosis on CTA was rated by two radiologists recently trained in CTA, and separately by an experienced colleague. Diagnostic performance of CTA was calculated on segment, vessel, and patient levels, using ICA as a reference. Segments with a proximal reference diameter <2 mm or with stents were not analyzed. RESULTS: In 51 of 101 patients and 121 of 1280 segments, ICA detected coronary stenosis. In 274 of 1280 (21%) segments, CTA had non-diagnostic image quality, the main reasons being severe calcifications (49%), motion artifacts associated with high or irregular heart rate (45%), and low contrast opacification (14%). Significantly more women (43%) had non-diagnostic scans compared to men (20%). A heart rate above 60 beats per minute was associated with significantly more non-diagnostic patients (38% vs. 18%). In the 1006 diagnostic segments, CTA had a sensitivity of 78%, specificity of 95%, positive predictive value (PPV) of 54%, and negative predictive value (NPV) of 98% for detecting significant coronary stenosis. In 29 patients, CTA was non-diagnostic. In the remaining 72 patients, sensitivity was 100%, specificity 65%, PPV 79%, and NPV 100%. The use of a more experienced CTA reader did not improve diagnostic performance. CONCLUSION: CTA had a very high negative predictive value, but the number of non-diagnostic scans was high, especially in women. The main limitations were motion artifacts and vessel calcifications, while short experience in CTA did not influence the interpretation.

Assessment of a daily online implanted fiducial marker-guided prostate radiotherapy process.

The aims of this study were to investigate whether intrafraction prostate motion can affect the accuracy of online prostate positioning using implanted fiducial markers and to determine the effect of prostate rotations on the accuracy of the software-predicted set-up correction shifts. Eleven patients were treated with implanted prostate fiducial markers and online set-up corrections. Orthogonal electronic portal images were acquired to determine couch shifts before treatment. Verification images were also acquired during treatment to assess whether intrafraction motion had occurred. A limitation of the online image registration software is that it does not allow for in-plane prostate rotations (evident on lateral portal images) when aligning marker positions. The accuracy of couch shifts was assessed by repeating the registration measurements with separate software that incorporates full in-plane prostate rotations. Additional treatment time required for online positioning was also measured. For the patient group, the overall postalignment systematic prostate errors were less than 1.5 mm (1 standard deviation) in all directions (range 0.2-3.9 mm). The random prostate errors ranged from 0.8 to 3.3 mm (1 standard deviation). One patient exhibited intrafraction prostate motion, resulting in a postalignment prostate set-up error of more than 10 mm for one fraction. In 14 of 35 fractions, the postalignment prostate set-up error was greater than 5 mm in the anterior-posterior direction for this patient. Maximum prostate rotations measured from the lateral images varied from 2 degrees to 20 degrees for the patients. The differences between set-up shifts determined by the online software without in-plane rotations to align markers, and with rotations applied, was less than 1 mm (root mean square), with a maximum difference of 4.1 mm. Intrafraction prostate motion was found to reduce the effectiveness of the online set-up for one of the patients. A larger study is required to determine the magnitude of this problem for the patient population. The inability in the current software to incorporate in-plane prostate rotations is a limitation that should not introduce large errors, provided that the treatment isocentre is positioned near the centre of the prostate.

The use of self-expanding metal stents to treat acute esophageal variceal bleeding.

BACKGROUND AND STUDY AIMS: Acute variceal bleeding is a life-threatening complication of liver cirrhosis. Essential factors for survival after variceal bleeding are the rapidity and efficacy of initial primary hemostasis. Endoscopic and vasoactive therapy is the gold standard in the management of acute variceal hemorrhage. The primary aim of this study was to evaluate the use of self-expandable metallic stents to arrest uncontrollable acute variceal bleeding. PATIENTS AND METHODS: Between November 2002 and May 2005, esophageal stents were implanted in 20 patients (18 men, two women; mean age 52, range 27-87) with massive ongoing bleeding from esophageal varices, as an alternative treatment to balloon tamponade. The patients had not been successfully managed with prior pharmacologic or endoscopic therapy. They had had one to five previous bleeding episodes (mean 2.4). Eight of the patients were in Child-Pugh grade B and 12 in grade C. A new type of stent with special introducers was developed that allowed placement without radiographic assistance. RESULTS: The stents were successfully placed in all of the patients and were left in place for 2-14 days. Bleeding from the esophageal varices ceased immediately after implantation of the stent in all cases. While the stent was in place, further diagnostic steps were carried out to optimize management of the patients' illness and portal hypertension. No recurrent bleeding, morbidity, or mortality occurred during treatment with the esophageal stent. All of the stents were extracted without any complications after definitive treatment had been started. CONCLUSIONS: In this pilot study, the new method of implantation of an esophageal stent was found to be a safe and effective treatment for massive bleeding from esophageal varices in patients with liver cirrhosis. These initial clinical results will of course have to be confirmed in comparative studies including a large number of patients.

Novel technique of laparoscopic azygoportal disconnection for treatment of esophageal varicosis: preliminary experience with five patients.

BACKGROUND: Liver cirrhosis leads frequently to the development of ascites and a formation of varicose veins in the esophagus. The latter presents increased mortality risk. Recently, significant progress in laparoscopic technology enabled devascularization of the proximal stomach in a less invasive way. The results experienced by five patients are presented. METHODS: Laparoscopic azygoportal disconnection was performed by means of novel technique (Danis procedure) in five men with esophagus varices bleeding (2nd to 11th events) and liver cirrhosis stage Child-Pugh B and C. This procedure was performed after all other methods had either failed to prevent recurrent bleeding or were refused by the patient. Five ports were positioned on the upper abdominal wall. The veins in the lesser omentum were divided by means of the LigaSure-Atlas device. The stomach coronary vein was visualized, and all the proximal branches toward the esophagus as well as the short gastric vessels were divided. The diaphragm hiatus was opened, and the distal esophagus was dissected. The paraesophageal venous collaterals also were divided, and the remaining varicose veins of the esophagus were interrupted by transmural stitching. RESULTS: All the patients survived the minimally invasive procedure. Two of them died 9 and 16 months after surgery, respectively, because of liver insufficiency. No bleeding event from varicose veins in the esophagus occurred postoperatively. CONCLUSION: Laparoscopic azygoportal disconnection is a less invasive method for prevention of rebleeding from varicose veins in the esophagus. Further studies are necessary to confirm these preliminary results.

Treatment of refractory chronic depression and dysthymia with high-dose thyroxine.

BACKGROUND: An 8-week open trial was conducted to investigate whether patients with treatment-resistant, chronic depression and/or dysthymia could profit from high-dose thyroxine (T4) augmentation. METHODS: Nine patients whose current depressive episode had lasted for a mean of 15.5 +/- 8.6 months (range: 2-30 months) received T4 in addition to their current medication. RESULTS: Two patients dropped out of the study owing to side effects. The remaining 7 patients received a final mean dose of T4 of 235 +/- 58 micrograms/day (range: 150-300 micrograms/day). Their scores on the Hamilton Depression Rating Scale had fallen from a mean of 21.1 +/- 4.1 before inclusion in the study to a mean of 8.0 +/- 2.8 at the end of the 8th week. Five patients were full responders, 1 a partial responder, and 1 a nonresponder. CONCLUSIONS: Augmentation with high-dose T4 proved to have an antidepressant effect in more than 50% of the previously treatment-resistant patients with chronic depression and/or dysthymia.

Sleep quality during alcohol withdrawal with bright light therapy.

1. Alcohol withdrawal is a complex syndrome that ranges from anxiety, insomnia to delirium tremens. Common treatment is the application of sedative medication. Exposure to bright light in the daytime should advance the normal sleep/wake cycle and moreover it should improve the availability of man's adaptive behavior during alcohol withdrawal. 2. This pilot study describes bright light therapy (BL) during alcohol withdrawal in ten alcohol dependent patients (DSM-III-R: 291.80) without any sedative medication. BL (3000 Lux) was administered on day 3 of abstinence between 7.00-9.00 a.m. and 5.00-9.00 p.m. Total-sleep-polysomnography (recordings between 10.30 p.m.-6.00 a.m.) and self-rating scale were performed to compare intraindividual changes during three nights. After one adaptation night (immediately after alcohol withdrawal), one baseline night and one "BL-night" and one "post-BL night" were analysed. 3. At baseline, total sleep time and sleep efficiency were severely deteriorated, but tended to improve in the following nights after BL. Sleep onset latency showed a significant decline after BL. Stages 3 and 4 were reduced at baseline. Latencies to slow wave sleep were significantly shortened after BL. REM increased in the nights after BL. Subjective sleep quality improved after BL. Although the present results, bright light having a possible stabilizing effect on sleep maintenance and sleep architecture during acute alcohol withdrawal, the authors could only derive hypotheses for further ongoing controlled investigations using placebo light, to receive final verification.

Disrupted melatonin-secretion during alcohol withdrawal.

1. The synthesis of the pineal hormone, melatonin, is under adrenergic control. The brain's rhythm generating system (suprachiasmatic nucleus and associated systems) which is synchronised by the light-dark cycle controls norepinephrine release from the sympathetic nerve terminal resulting in cAMP accumulation. Increased cAMP leads to induction of the rate-limiting enzyme, N-acetyltransferase and synthesis of melatonin. The pineal exhibits a circadian rhythm with highest blood levels of the hormone being present during the night. The circadian rhythm of melatonin production provides important time-of-day and time-of-year information and, as a result, this hormonal cycle drives other 24-hour rhythms as well as seasonal cycles of reproduction, at least in photoperiodic mammals. 2. Chronic alcoholics were withdrawn from alcohol during a continued period of 4 days and nights. Blood samples were drawn from an indwelling venous catheter and sleep was monitored with polysomnography. No medication was used. No alcohol intake was allowed after admission. Bright light treatment was applied during day 3 of the study. 3. During the 4 days of alcohol-withdrawal the night time melatonin-secretion was disrupted. More than 50% of the patients had a very low secretion (< 30 pg/ml) which did not normalize during the study period. Psychopathology, sleep quality and sleep architecture improved significantly. The melatonin secretion pattern showed low values throughout the study. This low melatonin secretion might reflect the long lasting toxic influence of alcohol on the biological clock and/or a direct inhibitory effect on pineal function. These are different effects, although interrelated. 4. Ethanol has a direct inhibitory effect on pineal melatonin synthesis. A well-recognized action of ethanol is its ability to permeate and perturb the structure of cell membranes and may be related to its lipophilic properties. The changes in membrane fluidity seem to last longer than the study period of 4 days.

Immunoturbidimetric determination of lipoprotein(a): improvement in the measurement of turbid and triglyceride-rich samples.

Immunoturbidimetry (IT), a widely used method in clinical chemical laboratories, was checked for its suitability for lipoprotein(a) (Lp(a)) quantification. When the conventional sample diluents were used, turbidimetry gave false results particularly with frozen or lipemic sera which correlated poorly with electroimmunodiffusion (EID). L-Proline which is known to dissociate Lp(a) from other apo B-containing lipoproteins improved the results considerably. One hundred frozen sera were investigated in IT with and without the addition of L-proline to the sample diluent. EID served as a comparison method. In a method comparison (IT vs. EID) linear regression analysis improved from r = 0.793: y = 0.89x - 9.4 (without L-proline) to r = 0.949: y = 0.98x + 4.8 (with L-proline). The improvement of the correlation of the two methods was most pronounced in sera with triglyceride values exceeding 5.5 mmol/l. The IT assay described here was linear between 50 and 1100 mg/l. Total imprecision (coefficient of variation) was below 10%. The assay was not affected by the addition of LDL or plasminogen to the samples. The Lp(a) concentration of the calibrator, i.e. a secondary standard serum, was compared with that of a purified primary Lp(a) standard which consisted of a mixture of four apo(a) isoforms. Total Lp(a) mass (lipids, protein, carbohydrates) was determined chemically and was compared with the Lp(a) mass determined immunochemically by IT and EID. Recovery of the purified Lp(a) was 106% (range 90-116%) in IT and 102% (range 91-115%) in EID. Dose response curves from pure single isoforms (S1 and S4), calibrator and serum samples were parallel. We consider IT to be a simple and rapid method for Lp(a) quantification which is not biased by different apo(a) isoforms.

Immunochemical determination of lipoprotein Lp(a): comparison of Laurell electrophoresis and ELISA.

The lipoprotein Lp(a) concentrations in serum from 520 persons (317 men and 203 women) were measured by two different Laurell electrophoresis assays (one in house and one commercial) and by an ELISA technique, using polyclonal antibodies from two different animal species. The following results were obtained. 1. The two Laurell techniques gave similar results. The mean values of all three methods were comparable, whereas median values obtained by ELISA were markedly lower (0.85, 0.97 and 0.057 g/l for the two Laurell assays and the ELISA, respectively). 2. All three methods correlated very well with a correlation coefficient of greater than 0.95. 3. Women had significantly higher values than men (p less than 0.01). It was concluded that Lp(a) serum concentrations in the 'pathological range' could be measured with high enough precision by Laurell electrophoresis and by ELISA using polyclonal antibodies from different animal species.