Extraperitoneal placement of the bladder-drained pancreas transplant: why not?
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Biomedical subjects
Publications and source records attributed to C Jacobs.
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Assessment of normalized dialysis dose Kt/V actually delivered to the patient carries the drawback of requiring several blood or dialysate samplings and urea concentration measurements. In order to easily quantify Kt/V, we validate here the routine implementation of an original technique for the non-invasive, on-line, and fully automatic estimation of total mean urea clearance. This estimation is obtained from the measurement by a conductivity method of the effective ionic dialysance DR, which is the dialysance of electrolytes taking into account ultrafiltration and recirculation. The observed increase in DR with ultrafiltration rate and decrease in DR with elevation of access recirculation ratio show that the estimation of DR is affected by ultrafiltration and recirculation in a consistent manner. The mean value Keff of ionic dialysance DR was compared with the value Kdc of effective urea clearance obtained by dialysate collection during 12 haemodialysis sessions. The similarity (magnitude of variation 5%) between the ionic dialysance Keff and the effective urea clearance Kdc supports the validity of the equivalence between the transfer characteristics of electrolytes and urea through the dialyser membrane. Given an estimate of the urea distribution volume V, this estimation of effective urea clearance by ionic dialysance measurement allows an on-line estimation of the normalized dialysis dose Kt/V actually delivered to the patient.
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A mechanism for bacteria to monitor the status of their vital cell wall peptidoglycan is suggested by the convergence of two phenomena: peptidoglycan recycling and beta-lactamase induction. ampG and ampD, genes essential for beta-lactamase regulation, are here shown to be required for recycling as well. Cells lacking either AmpG or AmpD lose up to 40% of their peptidoglycan per generation, whereas Escherichia coli normally suffers minimal losses and instead recycles 40 or 50% of the tripeptide, L-alanyl-D-glutamyl-meso-diaminopimelic acid, from its peptidoglycan each generation. The ampG mutant releases peptidoglycan-derived material into the medium. In contrast, the ampD mutant accumulates a novel cell wall muropeptide, 1,6-anhydro N-acetylmuramyl-L-alanyl-D-glutamyl-meso-diaminopimelic acid (anhMurNAc-tripeptide), in its cytoplasm. This work suggests that AmpG is the permease for a large muropeptide and AmpD is a novel cytosolic N-acetylmuramyl-L-alanine amidase that cleaves anhMurNAc-tripeptide to release tripeptide, which is then recycled. These results also suggest that the phenomenon of beta-lactamase induction is regulated by the level of muropeptide(s) in the cytoplasm, since an ampD mutation that results in beta-lactamase expression even in the absence of a beta-lactamase inducer coincides with accumulation of anhMurNAc-tripeptide. The transcriptional regulator AmpR is presumably converted into an activator for beta-lactamase production by sensing the higher level of muropeptide(s). This may be an example of a general mechanism for signaling the progress of external events such as cell wall maturation, cell division or cell wall damage.
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Nephrotoxicity is the most common and important side-effect of cyclosporin (CsA) therapy. CsA alters renal haemodynamics with a reduction in renal blood flow (RBF) and glomerular filtration rate (GFR) and a significant increase in renal vascular resistances (RVR). The present experimental study investigates whether verapamil or atrial natriuretic factor (ANF) are able to prevent the nephrotoxicity of CsA. All studies were conducted in an in-situ autoperfused rat kidney model which allows continuous measurement of renal blood flow without dissection of the renal artery. CsA as a 40 mg/kg bolus dose significantly decreased RBF (from 2.15 +/- 0.1 and 2.19 +/- 0.1 before CsA, to 1.29 +/- 0.16 ml/min/100 g BW, 60 min after CsA administration) (P < 0.05), and GFR (from 0.14 +/- 0.1 and 0.13 +/- 0.01 before CsA, to 0.08 +/- 0.01 ml/min/100 g BW, 60 min after CsA administration) (P < 0.05). CsA significantly increased RVR (from 9.5 +/- 0.73 and 9.8 +/- 0.78 before CsA, to 16.7 +/- 2.9 mmHg x min/ml 60 min after CsA administration) (P < 0.05). Verapamil pretreatment (as continuous intrarenal infusion at the rate of 1.25 micrograms/kg/min) attenuated the fall in GFR (from 0.16 +/- 0.01 and 0.19 +/- 0.03 ml/min/100 g before CsA to 0.20 +/- 0.05 ml/min/100 g BW, 60 min after CsA administration) (NS) and in RBF (from 2.42 +/- 0.2 and 2.6 +/- 0.22 ml/min/100 g before CsA to 1.79 +/- 0.17 ml/min/100 g BW, 60 min after CsA administration (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
In some patients suffering from rheumatoid arthritis (RA), vasculitis is a clear clinical manifestation, mentioned as rheumatoid vasculitis (RV). Autoantibodies directed against endothelial cells (AEA) have been implicated in the pathogenesis of this disorder, and it has been suggested in a number of studies that testing for AEA should be included in diagnosing RV. To test this hypothesis, we have evaluated the presence of AEA in sera of patients suffering from various autoimmune diseases, employing an ELISA with fixed cultured endothelial cells (EC). In all the groups of patients ELISA-positive sera were present. A significant difference in percentage of positivity was found between the RA and RV group (P < 0.05). In addition, our results indicated that not only antibodies directed against antigens on the EC membrane were detected, but also antibodies directed against intracellular components like DNA, histones and cytoskeletal components. Therefore, we also tested all these patient sera on unfixed intact EC using indirect immunofluorescence followed by FACS analysis. Whereas in the total patient population 34 out of 65 patients were AEA-positive as determined in the ELISA, only seven patients were weakly positive when examined by flow cytometry. We conclude that: (i) an ELISA on fixed EC does not specifically detect AEA. A positive test result is, however, to some extent correlated with the occurrence of vasculitis, and may therefore be helpful in diagnosing this disease; (ii) FACS analysis is a more suitable method than ELISA to measure the presence of membrane-specific AEA in patient sera; (iii) specific IgG-AEA are less common in patients suffering from autoimmune disorders than was assumed previously.
Although the acute nephrotoxicity of cisplatin has been well documented, long-term follow-up studies are scanty. We have evaluated the renal function in 35 patients who have had completed therapy with cisplatin at least 3 months before the study. All patients had normal serum creatinine levels before chemotherapy. Evaluation of renal function included: serum creatinine, glomerular filtration rate (inulin clearance), effective renal plasma flow (p-aminohippurate clearance), urinary beta 2-microglobulin and N-acetyl-beta-D-glucosaminidase excretion, and renal tomography. The median cumulated dose of cisplatin was 603 +/- 37 mg/m2. The mean serum creatinine level was 78 +/- 21 and 88 +/- 3 mumol/l before and after chemotherapy, respectively (p < 0.05). Mean glomerular filtration rate (92 +/- 4 ml/min) and effective renal plasma flow (362 +/- 21 ml/min) were significantly lower than in controls (110 +/- 3 and 436 +/- 24 ml/min). The mean enzymuria and the renal size remained within the normal range. In 12 patients who were reevaluated 12 and 24 months later, glomerular filtration rate and effective renal plasma flow remained stable. These results suggest that at usual dosages cisplatin is associated with a nonprogressive loss of renal function which is of a moderate degree.
Low-molecular-weight heparins (LMWHs) are used to prevent clotting in hemodialysis extracorporeal blood circuits. In order to test the possibility of using reviparine (a LMWH of 3,900 D) in this indication, we studied the pharmacokinetics of the drug after a mean dose of 3,300 IU anti-Xa in 10 hemodialyzed patients. Reviparine was administered subcutaneously between two dialysis sessions and intravenously at the start of 20 dialysis sessions performed either with high (HP) or low-permeability (LP) membranes. We observed a moderate increase of the elimination half-life of reviparine (T1/2: 5 +/- 1.6 h between dialysis, 3.6 +/- 1.3 during dialysis with an HP membrane and 4.7 +/- 1.8 during dialysis with an LP membrane) versus 3.3 +/- 1 in healthy volunteers. Dialysis procedures with an HP or an LP membrane do not importantly modify the pharmacokinetics of reviparin compared with data observed in healthy volunteers. During the sessions, we observed no clotting in the extracorporeal circuit, no hemorrhagic event and no prolongation of the fistula compression times. Further clinical studies are required to define the optimal dosage of reviparine to prevent coagulation in hemodialysis blood circuits.