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Background: To compare image quality, metal artifacts, and diagnostic confidence of conventional computed tomography (CT) images of unilateral total hip arthroplasty patients (THA) with deep learning-based metal artifact reduction (DL-MAR) to conventional CT and 130-keV monoenergetic images with and without orthopedic metal artifact reduction (O-MAR). Methods: Conventional CT and 130-keV monoenergetic images with and without O-MAR and DL-MAR images of 28 unilateral THA patients were reconstructed. Image quality, metal artifacts, and diagnostic confidence in bone, pelvic organs, and soft tissue adjacent to the prosthesis were jointly scored by two experienced musculoskeletal radiologists. Contrast-to-noise ratios (CNR) between bladder and fat and muscle and fat were measured. Wilcoxon signed-rank tests with Holm-Bonferroni correction were used. Results: Significantly higher image quality, higher diagnostic confidence, and less severe metal artifacts were observed on DL-MAR and images with O-MAR compared to images without O-MAR (p < 0.001 for all comparisons). Higher image quality, higher diagnostic confidence for bone and soft tissue adjacent to the prosthesis, and less severe metal artifacts were observed on DL-MAR when compared to conventional images and 130-keV monoenergetic images with O-MAR (p ≤ 0.014). CNRs were higher for DL-MAR and images with O-MAR compared to images without O-MAR (p < 0.001). Higher CNRs were observed on DL-MAR images compared to conventional images and 130-keV monoenergetic images with O-MAR (p ≤ 0.010). Conclusions: DL-MAR showed higher image quality, diagnostic confidence, and superior metal artifact reduction compared to conventional CT images and 130-keV monoenergetic images with and without O-MAR in unilateral THA patients. Relevance statement: DL-MAR resulted into improved image quality, stronger reduction of metal artifacts, and improved diagnostic confidence compared to conventional and virtual monoenergetic images with and without metal artifact reduction, bringing DL-based metal artifact reduction closer to clinical application. Key points: • Metal artifacts introduced by total hip arthroplasty hamper radiologic assessment on CT. • A deep-learning algorithm (DL-MAR) was compared to dual-layer CT images with O-MAR. • DL-MAR showed best image quality and diagnostic confidence. • Highest contrast-to-noise ratios were observed on the DL-MAR images. [ABSTRACT FROM AUTHOR]

Background: Double inversion recovery (DIR) MRI has the potential to accentuate the synovium without using contrast agents, as it allows simultaneous signal suppression of fluid and fat. The purpose of this study was (1) to compare DIR MRI to conventional contrast-enhanced (CE) MRI for delineation of the synovium in the knee in children with juvenile idiopathic arthritis (JIA) and (2) to assess the agreement between DIR MRI and CE-MRI regarding maximal synovial thickness measurements. Results: In this prospective study, 26 children with JIA who consecutively underwent 3.0-T knee MRI between January 2018 and January 2021 were included (presence of knee arthritis: 13 [50%]; median age: 14 years [interquartile range [IQR]: 11–17]; 14 girls). Median confidence to depict the synovium (0–100 mm visual analogue scale; scored by 2 readers [consensus based]) was 88 (IQR: 79–97) for DIR MRI versus 100 (IQR: 100–100) for CE-MRI (p value = <.001). Maximal synovial thickness per child (millimeters; scored by 4 individual readers) on DIR MRI was greater (p value = <.001) in the children with knee arthritis (2.4 mm [IQR: 2.1–3.1]) than in those without knee arthritis (1.4 mm [IQR: 1.0–1.6]). Good inter-technique agreement for maximal synovial thickness per child was observed (rs = 0.93 [p value = <.001]; inter-reader reliability: ICC DIR MRI = 0.87 [p value = <.001], ICC CE-MRI = 0.90 [p value = <.001]). Conclusion: DIR MRI adequately delineated the synovium in the knee of children with JIA and enabled synovial thickness measurement similar to that of CE-MRI. Our results demonstrate that DIR MRI should be considered as a child-friendly alternative to CE-MRI for evaluation of synovitis in children with (suspected) JIA. [ABSTRACT FROM AUTHOR]

In two crossover studies with 12 (6 males/6 females) healthy young volunteers each, we compared the bioavailability of Neoimmun capsules with the microemulsion Neoral and the influence of a fat-rich breakfast on the bioavailability of Neoimmun. Each volunteer received a single dose of 200 mg cyclosporine A in each period. Blood samples were taken up to 24 h and analysed for cyclosporine A by high-performance liquid chromatography (HPLC) and photometric detection. The pharmacokinetic parameters were determined by non-compartmental analysis. The treatments were tested for bioequivalence and significant differences. The bioavailability of Neoimmun was significantly lower compared to Neoral, albeit Neoimmun met the bioequivalence criterion (90% confidence interval of AUC 0.80–0.94) or missed the criterion only marginally (90% confidence interval of c max 0.75–0.91). The bioavailability of Neoimmun as determined by area under the blood concentration-time curve (AUC) increased by nearly 20% after a fat-rich breakfast. However, mean peak concentrations after food were only higher in male subjects, whereas mean peak concentrations in female subjects were lower compared to fasting administration. In conclusion, our data show that Neoimmun exhibits a lower bioavailability than the microemulsion Neoral and that food has a significant but variable and sex-dependent impact on the bioavailability of Neoimmun capsules. [ABSTRACT FROM AUTHOR]

Objective: To investigate the influence of concomitant administration of roxithromycin on the plasma pharmacokinetics of lovastatin. Methods: In an open, randomized, crossover study, 12 healthy volunteers received 80 mg lovastatin orally either alone or concomitantly with 300 mg roxithromycin after 5-day pretreatment with roxithromycin 300 mg daily. Plasma concentrations of lovastatin (lactone and acid) were determined using high-performance liquid chromatography, and the pharmacokinetic parameters were estimated. Results: The mean (±SD) pharmacokinetic parameters of lovastatin lactone with and without roxithromycin were maximum concentration (Cmax) 8.49±6.80/16.3±9.4 ng ml–1, time to Cmax (tmax) 1.8±0.4/1.7±0.6 h, terminal plasma half-life (t1/2) 4.3±2.0/3.7±2.5 h, area under the plasma concentration–time curve from zero to infinity (AUC0–∞) 53±60/85±67 ng ml–1 h. The respective parameters of lovastatin acid were Cmax 24.6±13.4/17.8±11.0 ng ml–1, tmax 3.7±1.1/4.1±0.7 h, t1/2 3.2±2.5/4.3±2.8 h, AUC0–∞ 149±123/105±58 ng ml–1 h. Mean bioavailability of lovastatin lactone was lower and that of lovastatin acid was higher with concomitant treatment. However, the differences were significant only with respect to lovastatin lactone (AUC and Cmax) and Cmax of lovastatin acid. Conclusion: Roxithromycin does not influence the pharmacokinetics of lovastatin in such a way that dosage adjustment of lovastatin seems to be necessary during co-administration. [ABSTRACT FROM AUTHOR]

Objective: To study the effect of continuous veno-venous hemofiltration (CVVHF) on the pharmacokinetics of levofloxacin in critically ill patients with acute renal failure.Design: Open-label study.Setting: Anesthesiology ICU, University Hospital of Regensburg.Patients: Six critically ill patients treated with CVVHF because of acute renal failure needing antimicrobial therapy.Interventions: Levofloxacin i.v. 250 mg qd with a starting dose of 500 mg. CVVHF with the following characteristics: hemofilter AN69 hollow fibers of 0.90 m2 area, blood flow 150 ml/min, ultrafiltrate flow 1.3 l/h, filtrate substitution in post-dilution mode.Measurements and Results: The plasma pharmacokinetics and clearance of levofloxacin by hemofiltration were established on day 1 and day 4-6 of treatment. Levofloxacin was determined by high-performance liquid chromatography (HPLC). Mean (range) peak plasma concentrations after levofloxacin 500 mg single dose (s.d.) and 250 mg multiple dose (m.d.) were 6.4 (2.7-9.4) and 8.2 (4.7-10.3) mg/l, trough levels 2.7 (1.4-5.0) and 2.9 (1.7-3.9) mg/l, half-life 28 (19-38) and 22 (17-31) h, volume of distribution 1.2 (0.72-1.6) l/kg and 0.91 (0.52-2.0) l/kg, respectively. The mean sieving coefficient was 0.96 (0.79-1.09), mean total clearance 47 (20-89) ml/min, and mean clearance by hemofiltration 21 (13-27) ml/min, respectively.Conclusions: A dosage schedule of levofloxacin 250 mg qd with a 500 mg loading dose seems appropriate for anuric patients during CVVHF. Sufficiently high steady-state concentrations of levofloxacin were achieved after the first dose. Undesired accumulation of levofloxacin was not observed. [ABSTRACT FROM AUTHOR]

Parenteral cephalosporins are among the most frequently used antibiotics in hospital therapy. They are characterised by an extended spectrum of activity against Gram-positive and Gram-negative bacteria, and some also have good activity against anaerobes. They kill proliferating bacterial cells rapidly, and generally show only a low tendency to select resistant mutants. However, there are cephalosporin compounds which induce cephalosporinases very rapidly in certain microorganisms. Together with other β-lactam antibiotics, parenteral cephalosporins interfere with bacterial cell wall synthesis by inhibiting peptidoglycan cross-linkage. Because of this specific target, they are nontoxic to mammalian cells, and have a very favourable adverse effect profile. The chemical stability of parenteral cephalosporins in aqueous solution is good. After intravenous injection, high concentrations of these agents are achieved in serum and tissue. Most cephalosporins are eliminated unchanged via the kidney, with a half-life of 1 to 2 hours. But there are also derivatives with a serum half-life of more than 2 and up to 8 hours, allowing 12- or 24-hour dosage intervals. Because of their reliable efficacy and low risk of adverse effects, the parenteral cephalosporins offer a high degree of tolerability even in the setting of outpatient antibiotic therapy. In particular, the derivatives of the third generation are characterised by unique pharmacological properties. [ABSTRACT FROM AUTHOR]

Angiotensin-converting enzyme inhibitors and α1-adrenoceptor antagonists improve glucose disposal in diabetes mellitus. We compared the effect of the antihypertensive hybrid drug urapidil [α1-adrenoceptor antagonist serotonin 1A (5-hydroxytryptamine 1A, 5-HT1A) receptor agonist] on hyperglycemia in streptozotocin diabetic rats with the angiotensin-converting enzyme inhibitor ramipril. 5-HT1A receptor agonists induce hyperglycemia. This could be an important disadvantage during treatment of diabetes mellitus with urapidil. Diabetes was induced by streptozotocin (70 mg/kg i.p.). Treatment for 7 days (ramipril 10 mg/kg p.o.; urapidil 20 mg/kg p.o.) significantly decreased mean blood glucose values (urapidil: 15.7±0.9 mmol/l, P=0.007; ramipril: 15.0±0.8 mmol/l, P=0.038 vs. diabetic control group: 18.7±1.0 mmol/l). Both drugs reduced significantly blood pressure, urinary glucose, water consumption, and food requirement. Serotonin concentration in the brain (medulla oblongata, pituitary) was not affected. A normalization comparable with healthy control rats was observed only in a diabetic control group with insulin therapy. In conclusion, our results demonstrate that the antihypertensive drug urapidil has no detrimental effect on hyperglycemia compared with the angiotensin-converting enzyme inhibitor ramipril in experimental diabetes mellitus despite its 5-HT1A receptor agonistic properties. [ABSTRACT FROM AUTHOR]

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To study the role of peripheral catecholamines in plasma and different tissues in neurogenic hypertension we measured directly blood pressure, maximum rate of left ventricular pressure rise (dp/dt) and heart rate through an aortic catheter 5 weeks after total sino-aortic baroreceptor deafferentation in male Sprague-Dawley rats. Blood samples were collected through the same catheter to determine plasma catecholamine concentrations. Blood pressure and dp/dt were significantly higher in neurogenic-hypertensive rats when compared with sham operated rats. Plasma noradrenaline concentrations and plasma adrenaline concentrations reached significantly higher levels in neurogenic-hypertensive rats. In the heart noradrenaline content was lower (when calculated per g wet weight) and in the adrenal medulla adrenaline content was higher in neurogenic-hypertensive rats, when compared with sham operated controls. A significant positive correlation was found between dp/dt and plasma noradrenaline concentrations. It is concluded that sino-aortic baroreceptor deafferentation produces a significant chronic hypertension, probably supported by elevated plasma catecholamine concentrations and enhanced synthesis and release of adrenaline from adrenal medulla. [ABSTRACT FROM AUTHOR]

Copyright of Infection is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Infection is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Infection is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)