| 2431. |
- Eriksson, Victoria, et al.
(författare)
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Thromboembolic events during neoadjuvant chemotherapy in muscle invasive bladder cancer – any correlation to the central venous access? : A clinical practice article
- 2022
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Ingår i: F1000 Research. - : F1000 Research. - 2046-1402. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Patients with muscle invasive bladder cancer have a generally known 5-year overall survival of approximately 58% with neoadjuvant chemotherapy (NAC). During the last decades, addition of Cisplatinum-based NAC in fit patients prior to radical cystectomy (RC), has significantly improved OS, compared to RC only. However, some published studies following NAC addition, describe an intermediate risk increase of thromboembolic events (TEEs). Placement of central venous access (CVA) before NAC has also been suggested as being a potential risk factor for thrombosis. We present a combination of images and cases from the Northern Swedish health region where three patients developed venous TEE after CVA placement for NAC-administration and found that the time until curable RC was prolonged circa one month each, with an addition of one RC cancelled. These are serious events and to our knowledge, there are no current guidelines on prevention of TEE before RC. The aim with this report was to provide examples of these events and conclude that further prospective trials are warranted on prevention and future guidelines regarding venous anticoagulant treatment for TEE that occur pre-RC in NAC-patients.
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| 2432. |
- Erixon, Martin, et al.
(författare)
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3,4-dge in peritoneal dialysis fluids cannot be found in plasma after infusion into the peritoneal cavity.
- 2008
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Ingår i: Peritoneal Dialysis International. - 1718-4304. ; 28:3, s. 277-282
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Glucose degradation products (GDPs) are important in the outcome of peritoneal dialysis (PD) treatment. 3,4-dideoxyglucosone-3-ene (3,4-DGE) is the most cytotoxic GDP found in conventionally manufactured fluids and may, in addition, be recruited from 3-deoxyglucosone (3-DG). It is not known what happens with those GDPs in patients during PD. The aim of this study was to investigate if the 3,4-DGE and 3-DG in PD fluids can be found in plasma during treatment. DESIGN: PD patients were dialyzed with a conventional PD fluid containing 43 mumol/L 3,4-DGE and 281 mumol/L 3-DG. Parallel experiments were performed in rats as well as in vitro with human plasma. The rats were dialyzed with a PD fluid containing 100 mumol/L 3,4-DGE and 200 mumol/L 3-DG. RESULTS: The concentration of 3,4-DGE in the peritoneum decreased at a much higher rate than 3-DG during the dwell. 3,4-DGE was not, however, detected in the plasma of patients or rats during dialysis. The concentration of 3-DG in plasma peaked shortly after infusion of the fluid to the peritoneal cavity. The concentration of 3,4-DGE during experimental incubation in plasma decreased rapidly, while the concentration of 3-DG decreased only 10% as rapidly or less. CONCLUSION: 3,4-DGE could not be detected in plasma from either PD patients or rats during dialysis. This is presumably due to its high reactivity. 3-DG may, on the other hand, pass through the membrane and be detected in the blood.
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| 2433. |
- Erixon, Martin, et al.
(författare)
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3,4-dideoxyglucosone-3-ene in peritoneal dialysis fluids infused into the peritoneal cavity cannot be found in plasma.
- 2009
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Ingår i: Peritoneal Dialysis International. - 1718-4304. ; 29 Suppl 2, s. 28-31
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Glucose degradation products (GDPs) are important for the outcome of peritoneal dialysis (PD) treatment. The most cytotoxic GDP found in conventionally manufactured fluids, 3,4-dideoxyglucosone-3-ene (3,4-DGE), may in addition be recruited from 3-deoxyglucosone (3-DG). What happens with the GDPs in the fluid infused into patients during PD is not known. We investigated whether 3,4-DGE and 3-DG in PD fluid can be found in plasma during treatment. DESIGN: Patients on PD were dialyzed with a conventional PD fluid containing 43 micromol/L 3,4-DGE and 281 micromol/L 3-DG. Parallel experiments were performed in rats and in vitro with human plasma. The rats were dialyzed with a PD fluid containing 100 micromol/L 3,4-DGE and 200 micromol/L 3-DG. RESULTS: The 3,4-DGE concentration in the peritoneum declined at a much higher rate during the dwell than did the 3-DG concentration. However, 3,4-DGE was not detected in the plasma of patients or of rats during dialysis. The 3-DG concentration in plasma peaked shortly after infusion of fluid into the peritoneal cavity. The 3,4-DGE concentration during experimental incubation in plasma declined rapidly; the 3-DG concentration declined only 10% as rapidly (or less). CONCLUSION: During dialysis, 3,4-DGE could not be detected in plasma of either PD patients or rats, presumably because of its high reactivity. On the other hand, 3-DG may pass through the membrane and be detected in the blood.
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| 2434. |
- Erixon, Martin, et al.
(författare)
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How to avoid glucose degradation products in peritoneal dialysis fluids
- 2006
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Ingår i: Peritoneal Dialysis International. - 1718-4304. ; 26:4, s. 490-497
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The formation of glucose degradation products (GDPs) during sterilization of peritoneal dialysis fluids (PDFs) is one of the most important aspects of biocompatibility of glucose-containing PDFs. Producers of PDFs are thus trying to minimize the level of GDPs in their products. 3,4-Dideoxyglucosone-3-ene (3,4-DGE) has been identified as the most bioreactive GDP in PDFs. It exists in a temperature-dependent equilibrium with a pool of 3-deoxyglucosone (3-DG) and is a precursor in the irreversible formation of 5-hydroxymethyl furaldehyde (5-HMF). The aim of the present study was to investigate how to minimize GDPs in PDFs and how different manufacturers have succeeded in doing so. Design: Glucose solutions at different pHs and concentrations were heat sterilized and 3-DG, 3,4-DGE, 5-HMF, formaldehyde, and acetaldehyde were analyzed. Conventional as well as biocompatible fluids from different manufacturers were analyzed in parallel for GDP concentrations. Results: The concentrations of 3-DG and 3,4-DGE produced during heat sterilization decreased when pH was reduced to about 2. Concentration of 5-HMF decreased when pH was reduced to 2.6. After further decrease to a pH of 2.0, concentration of 5-HMF increased slightly, and below a pH of 2.0 it increased considerably, together with formaldehyde; 3-DG continued to drop and 3,4-DGE remained constant. Inhibition of cell growth was paralleled by 3,4-DGE concentration at pH 2.0-6.0. A high glucose concentration lowered concentrations of 3,4-DGE and 3-DG at pH 5.5 and of 5-HMF at pH 1. At pH 2.2 and 3.2, glucose concentration had a minor effect on the formation of GDPs. All conventional PDFs contained high levels of 3,4-DGE and 3-DG. Concentrations were considerably lower in the biocompatible fluids. However, the concentration of 5-HMF was slightly higher in all the biocompatible fluids. Conclusion: The best way to avoid reactive GDPs is to have a pH between 2.0 and 2.6 during sterilization. If pHs outside this range are used, it becomes more important to have There are large variations in GDPs, both within and between biocompatible and conventionally manufactured PDFs.
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| 2435. |
- Erixon, Martin, et al.
(författare)
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PD fluids contain high concentrations of cytotoxic GDPs directly after sterilization
- 2004
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Ingår i: Peritoneal Dialysis International. - 1718-4304. ; 24:4, s. 392-398
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Glucose degradation products (GDPs) in peritoneal dialysis (PD) fluids are cytotoxic and affect the survival of the peritoneal membrane. One of the most reactive GDPs in PD fluids is 3,4-dideoxyglucosone-3-ene (3,4-DGE). 3,4-DGE has been reported as an intermediate between 3-deoxyglucosone (3-DG) and 5-hydroxymethyl furaldehyde (5-HMF) during degradation of glucose. In PD fluids, 3,4-DGE exists in a temperature-dependent equilibrium with a pool of unidentified substances. The aim of this study was to explore this equilibrium and its temperature dependence during the first months of storage after the sterilization procedure. Methods: GDPs and inhibition of cell growth (ICG) were measured directly after sterilization of the PD fluid and during storage at different temperatures for 60 days. The following GDPs were analyzed: 3-DG, 3,4-DGE, 5-HMF, formaldehyde, acetaldehyde, glyoxal, and methylglyoxal. Results: Immediately after sterilization, the concentration of 3,4-DGE was 125 mumol/L. During the first weeks of storage, it decreased by about 80%. At the same time, the 3-DG concentration increased. None of the other GDPs were significantly affected. Cytotoxicity correlated well with the concentration of 3,4-DGE. When pure 3,4-DGE was substituted for the lost amount of 3,4-DGE after 30 days of storage, the initial ICG was almost completely regained. Conclusions: Heat sterilization of PD fluids promotes the formation of large quantities of 3,4-DGE, rendering the fluid highly cytotoxic. During storage, the main part of 3,4-DGE is reversibly converted in a temperature-dependent manner to a less cytotoxic pool, consisting mainly of 3-DG. Cytotoxicity seems to be dependent exclusively on 3,4-DGE. In order to avoid higher levels of 3,4-DGE concentrations, PD fluids should not be used too soon after sterilization and should not be stored at temperatures above room temperature.
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| 2436. |
- Erixon, Martin, et al.
(författare)
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Take care in how you store your PD fluids: Actual temperature determines the balance between reactive and non-reactive GDPs
- 2005
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Ingår i: Peritoneal Dialysis International. - 1718-4304. ; 25:6, s. 583-590
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Tidskriftsartikel (refereegranskat)abstract
- Objective: During heat sterilization and during prolonged storage, glucose in peritoneal dialysis fluids (PDF) degrades to carbonyl compounds commonly known as glucose degradation products (GDPs). Of these, 3,4-dideoxyglucosone-3-ene (3,4-DGE) is the most cytotoxic. It is an intermediate in degradation between 3-deoxyglucosone (3-DG) and 5-hydroxymethyl-2-furaldehyde (5-HMF). We have earlier reported that there seems to be equilibrium between these GDPs in PDF. The aim of the present study was to investigate details of this equilibrium. Methods: Aqueous solutions of pure 3-DG, 3,4-DGE, and 5-HMF were incubated at 40 degrees C for 40 days., Conventional and low-GDP fluids were incubated at various temperatures for up to, 3 weeks. Formaldehyde, acetaldehyde, glyoxal, methylglyoxal, 3-DG, 3,4-DGE, and 5-HMF were analyzed using high performance liquid chromatography. Results: Incubation of 100 mu mol/L 3,4-DGE resulted in the production of 36 mu mol/L 3-DG, 4 mu mol/L 5-HMF, and 40 mu mol/L unidentified substances. With the same incubation, 200 mu mol/L 3-DG was converted to 9 mu mol/L 3,4-DGE, 6 mu mol/L 5-HMF, and 14 mu mol/L unidentified substances. By contrast, 100 mu mol/L 5-HMF was uninfluenced by incubation. In a conventional PDF incubated at 60 degrees C for 1 day, the 3,4-DGE concentration increased from 14 to a maximum of 49 mu mol/L. When the fluids were returned to room temperature, the concentration decreased but did not reach original values until after 40 days. In a low GDP fluid, 3,4-DGE increased and decreased in the same manner as in the conventional fluid but reached a maximum of only 0.8 mu moL/L. Conclusions: Considerable amounts of 3,4-DGE maybe recruited by increases in temperature in conventional PDFs. Lowering the temperature will again reduce the concentration but much more time will be needed. Precursors for 3,4-DGE recruitment are most probably 3-DG and the enol 3-deoxyaldose-2-ene, but not 5-HMF. Considering the ease at which 3,4-DGE is recruited from its pool of precursors and the difficulty of getting rid of it again, one should be extremely careful with the temperatures conventional PDFs are exposed to.
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| 2437. |
- Evans, Marie, et al.
(författare)
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Glomerular filtration rate-estimating equations for patients with advanced chronic kidney disease
- 2013
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Ingår i: Nephrology Dialysis Transplantation. - : Oxford University Press (OUP). - 1460-2385 .- 0931-0509. ; 28:10, s. 2518-2526
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Tidskriftsartikel (refereegranskat)abstract
- Renal function is often estimated using one of several glomerular filtration rate (GFR) estimating equations. However, there is no consensus which estimating equation performs best in patients with advanced renal failure. We compared the performance of five different estimated GFR (eGFR) equations [Cockcroft-Gault, Modification of Diet in Renal Disease (MDRD), Chronic Kidney Disease (CKD) Epidemiology collaboration (CKD-EPI) and Mayo Clinic and Lund-Malm] with measured GFR (plasma iohexol clearance) in 2098 referred CKD patients with mGFR 30 mL/min/1.73 m(2). There were 398 patients with an mGFR 10 mL/min/1.73 m(2), 1974 with a measured GFR (mGFR) 1120 mL/min/1.73 m(2) and 749 patients with mGFR 2130 mL/min/1.73 m(2). Across the entire range, the median bias of eGFR was lowest for the Lund-Malm equation (0.7 mL/min/1.73 m(2)), followed by the CKD-EPI (1.2 mL/min/1.73 m(2)), the MDRD (1.6 mL/min/1.73 m(2)), Mayo Clinic equation (1.7 mL/min/1.73 m(2)) and Cockcroft-Gault equation (4.6 mL/min/1.73 m(2)). The best accuracy within 30 of mGFR was also for Lund-Malm (76), while it was similar for CKD-EPI, MDRD and Mayo (6567). The Cockcroft-Gault had the worst accuracy of only 54.The median bias was stable across mGFR categories, while the accuracy within 30 of mGFR became worse with decreasing mGFR. All equations performed best among patients with hereditary kidney diseases and tubulointerstitial disease. Accuracy was generally worse for patients 65 years of age and for those with diabetic nephropathy. In patients with advanced renal failure, the GFR-estimating equations show reasonably good performance on the population level. On the individual patient level, they are inaccurate, especially in elderly patients and those with diabetic nephropathy.
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| 2438. |
- Evans, Marc, et al.
(författare)
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The value of maintaining normokalaemia and enabling RAASi therapy in chronic kidney disease
- 2019
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Ingår i: BMC Nephrology. - : Springer Science and Business Media LLC. - 1471-2369. ; 20
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundPeople with chronic kidney disease (CKD) are at an increased risk of developing hyperkalaemia due to their declining kidney function. In addition, these patients are often required to reduce or discontinue guideline-recommended renin-angiotensin-aldosterone system inhibitor (RAASi) therapy due to increased risk of hyperkalaemia. This original research developed a model to quantify the health and economic benefits of maintaining normokalaemia and enabling optimal RAASi therapy in patients with CKD.MethodsA patient-level simulation model was designed to fully characterise the natural history of CKD over a lifetime horizon, and predict the associations between serum potassium levels, RAASi use and long-term outcomes based on published literature. The clinical and economic benefits of maintaining sustained potassium levels and therefore avoiding RAASi discontinuation in CKD patients were demonstrated using illustrative, sensitivity and scenario analyses.ResultsInternal and external validation exercises confirmed the predictive capability of the model. Sustained potassium management and ongoing RAASi therapy were associated with longer life expectancy (+ 2.36 years), delayed onset of end stage renal disease (+ 5.4 years), quality-adjusted life-year gains (+ 1.02 QALYs), cost savings (£3135) and associated net monetary benefit (£23,446 at £20,000 per QALY gained) compared to an absence of RAASi to prevent hyperkalaemia.ConclusionThis model represents a novel approach to predicting the long-term benefits of maintaining normokalaemia and enabling optimal RAASi therapy in patients with CKD, irrespective of the strategy used to achieve this target, which may support decision making in healthcare.
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| 2439. |
- Fabris, Linda, et al.
(författare)
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The Potential of MicroRNAs as Prostate Cancer Biomarkers.
- 2016
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Ingår i: European Urology. - : Elsevier BV. - 1873-7560 .- 0302-2838. ; 70:2, s. 312-322
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Forskningsöversikt (refereegranskat)abstract
- Short noncoding RNAs known as microRNAs (miRNAs) control protein expression through the degradation of RNA or the inhibition of protein translation. The miRNAs influence a wide range of biologic processes and are often deregulated in cancer. This family of small RNAs constitutes potentially valuable markers for the diagnosis, prognosis, and therapeutic choices in prostate cancer (PCa) patients, as well as potential drugs (miRNA mimics) or drug targets (anti-miRNAs) in PCa management.
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| 2440. |
- Falconer, C, et al.
(författare)
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Paraurethral connective tissue in stress-incontinent women after menopause
- 1998
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Ingår i: Acta Obstetricia et Gynecologica Scandinavica. - 0001-6349. ; 77:1, s. 95-100
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To study whether stress urinary incontinence after menopause is correlated to changes in the paraurethral connective tissue ultrastructure and metabolism.METHODS: Transvaginal biopsies were obtained from the paraurethral connective tissue in stress urinary incontinent women after menopause with and without estrogen replacement therapy, and from comparable controls. All the stress-incontinent women underwent urodynamic investigation. In the specimens, collagen concentration, measured as hydroxyproline, and the degree of extractability by pepsin digestion, were quantified. Proteoglycan composition and concentration were analyzed using Alcian Blue precipitation, followed by electro-phoretic separation and quantification. Using Northern blots, mRNA levels for the collagens I and III, the small proteoglycans decorin and biglycan, and the large proteoglycan versican, were quantified. Collagen structure was examined with transmission electron microscopy, and the diameters of collagen fibrils were analyzed with an interactive image analysis system (IBAS, Zeiss/Kontron).RESULTS: No significant difference in paraurethral connective tissue biochemistry or ultrastructure was registered between women with stress incontinence and controls. Estrogen replacement therapy resulted in a lower collagen concentration both between the controls (p = 0.02) and between the incontinent women (0.02). In the women with stress incontinence also the extractability by pepsin digestion was higher in the group with estrogen treatment (p = 0.004), indicating a decrease in cross-linking. The proteoglycan/collagen ratio was higher in the control group with estrogen treatment compared to untreated (p = 0.02), but no difference was found between estrogen treated and untreated incontinent women. The median collagen fibril diameter was 15% larger in the incontinent group of women without estrogen therapy compared to the control group and 5% larger when comparing the incontinent group on estrogen replacement therapy to the corresponding control group.CONCLUSION: The extracellular matrix of paraurethral connective tissue in stress urinary incontinent women after menopause reacted differently to estrogen replacement therapy compared to continent controls. In contrast to incontinent women of fertile age no major changes in collagen metabolism were found in stress urinary incontinent women after menopause.
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