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Willem Weimar

Publications and source records attributed to Willem Weimar.

At least 73 records · Page 4Linked to original sources
PubMed2003

Formation of donor-specific human leukocyte antigen antibodies after kidney transplantation: correlation with acute rejection and tapering of immunosuppression.

BACKGROUND: Before kidney transplantation, a serological crossmatch is routinely performed between donor and recipient to prevent hyperacute rejection by donor-specific anti-human leukocyte antigen (HLA) antibodies. After transplantation, the presence of these antibodies is not routinely monitored. We wanted to know whether donor-specific anti-HLA antibodies are detectable during acute rejection (AR), before or after reduction of immunosuppression in kidney transplant recipients who were converted from cyclosporine A (CsA) to the less nephrotoxic azathioprine (AZA) or mycophenolate mofetil (MMF) at 1 year after transplantation. METHODS: Plasma samples were collected before transplantation, at several time points after transplantation, and during AR. Antibodies were measured in 29 patients: 5 patients with AR during the first year after transplantation (before conversion), 14 patients with AR after conversion or dose-reduction of AZA or MMF, and a control group of 10 patients without AR during a follow-up of 2 years (1 year before and 1 year after conversion of immunosuppression). Antibodies were measured by complement-dependent cytotoxicity assay, enzyme-linked immunosorbent assay (ELISA), and flow-cytometry in a crossmatch with donor spleen cells. RESULTS: Donor-specific antibodies were not detectable after transplantation in the control group without AR, nor in patients with AR shortly after transplantation during CsA therapy. After conversion from CsA to AZA or MMF, antibodies appeared only in one patient after graft failure followed by transplantectomy and in patients during AR on AZA but not on MMF therapy. CONCLUSION: In this patient group, we could not detect donor-specific antibodies during CsA treatment, not even at the time of AR using three different techniques. Donor-specific antibodies were primarily present during AR in patients converted from CsA to AZA and were not found in the sera from patients converted to MMF.

Acute Disease↗
PubMed2003

Oral ulcers in kidney transplant recipients treated with sirolimus and mycophenolate mofetil.

BACKGROUND: In an attempt to reduce calcineurin inhibitor toxicity, transplant patients treated with tacrolimus can be switched to maintenance treatment with sirolimus. METHODS: In a prospective, randomized, multicenter trial, 33 kidney transplant recipients on steroid-free maintenance treatment with tacrolimus and mycophenolate mofetil continued tacrolimus and mycophenolate mofetil (control group, n=18) or were converted from tacrolimus to sirolimus (study group, n=15) at 1 year after transplantation. RESULTS: The study was prematurely stopped as a result of a cluster of nine patients suffering from painful oral ulcerations in the study group. Oral ulcerations did not occur in the control group. The authors here report on the individual cases suffering from this side effect of the instituted immunosuppressive regimen. CONCLUSIONS: The authors review the literature with respect to the occurrence of oral ulcers associated with the use of sirolimus or mycophenolate mofetil and speculate on the causes of the high incidence of oral ulcers in their study group. Possible explanations are overimmunosuppression during the period of the conversion from tacrolimus to sirolimus without antiviral prophylaxis, the use of the oral emulsion instead of tablets, or the lack of corticosteroid co-administration.

Adult↗
PubMed2003

Living kidney donors and hypoxia-inducible factor-1alpha.

BACKGROUND: Hypoxia inducible factor (HIF)-1, a heterodimeric transcription factor composed of alpha and beta subunits, is induced in the adaptive response to hypoxia and is critical for initiating the transcriptional activation of growth factors. We speculate that prolonged ischemia and hypoxia time leads to the production of HIF-1alpha, which in turn induces the production of fibrogenic cytokines in the graft. METHODS: To investigate our hypothesis, we measured the expression of HIF-1alpha in time-zero biopsy specimens from living-donor kidneys (< or =2.5 hr of ischemia) and cadaveric donor kidneys (12-32 hr of ischemia). RESULTS: By real time reverse-transcriptase polymerase chain reaction analysis, the mRNA expression level of HIF-1alpha was fivefold lower in time-zero biopsy specimens from living-donor kidneys than in specimens from cadaveric donor kidneys. In these time-zero biopsy specimens, the mRNA expression level of the fibrogenic cytokine transforming growth factor-beta was also significantly lower (twofold). CONCLUSIONS: Low HIF-1alpha mRNA expression levels correlate with short ischemia times and prevent the transcription of fibrogenic cytokines that initiate the irreversible process of graft fibrosis.

Biopsy↗
PubMed2003

Genetic polymorphisms of the CYP3A4, CYP3A5, and MDR-1 genes and pharmacokinetics of the calcineurin inhibitors cyclosporine and tacrolimus.

BACKGROUND: The calcineurin inhibitors cyclosporine (INN, cyclosporin) and tacrolimus have a narrow therapeutic index and show considerable interindividual variability in their pharmacokinetics. The low oral bioavailability of calcineurin inhibitors is thought to result from the actions of the metabolizing enzymes cytochrome P450 (CYP) 3A4 and CYP3A5 and the multidrug efflux pump P-glycoprotein, encoded by MDR-1. OBJECTIVE: Our objective was to determine the role of genetic polymorphisms in CYP3A4, CYP3A5, and MDR-1 with respect to interindividual variability in cyclosporine and tacrolimus pharmacokinetics. METHODS: Kidney transplant recipients receiving cyclosporine (n = 110) or tacrolimus (n = 64) were genotyped for CYP3A4*1B and *3, CYP3A5*3 and *6, and MDR-1 C3435T. Dose-adjusted trough levels were determined and correlated with the corresponding genotype. RESULTS: Tacrolimus dose-adjusted trough levels were higher in CYP3A5*3/*3 patients (n = 45) than in *1/*3 plus *1/*1 patients (n = 17), as follows: median and range, 94 (34-398) ng/mL per mg/kg versus 61 (37-163) ng/mL per mg/kg (P <.0001, Mann-Whitney test). CYP3A4*1B allele carriers (n = 10) had lower tacrolimus dose-adjusted trough levels compared with those in patients with the wild-type (*1/*1) genotype (n = 54): median and range, 57 (40-163) ng/mL per mg/kg versus 89 (34-398) ng/mL per mg/kg) (P =.003, Mann-Whitney test). No evidence was found supporting a role for the MDR-1 C3435T polymorphism in tacrolimus dose requirement. None of the polymorphisms studied correlated with cyclosporine dose-adjusted predose concentrations. CONCLUSION: As a group, patients with the CYP3A5*3/*3 genotype require less tacrolimus to reach target predose concentrations compared with CYP3A5*1 allele carriers, whereas CYP3A4*1B carriers require more tacrolimus to reach target trough concentrations compared with CYP3A4*1 homozygotes.

Calcineurin Inhibitors↗
PubMed2003

Hemodynamic response to lower body negative pressure in hemodialysis patients.

BACKGROUND: Hypovolemia is thought to have an important role in the pathogenesis of dialysis-related hypotension. METHODS: We studied the effect of hypovolemia simulated by lower body negative pressure (LBNP) in 11 hypotension-prone (HP) and 11 hypotension-resistant (HR) hemodialysis patients. LBNP was applied stepwise from 0 to -20 to -40 mm Hg. Systolic arterial pressure, heart rate, and central venous pressure (CVP) were recorded continuously after cannulation of the right jugular vein. Stroke volume index was measured at each step echocardiographically. At the end of each level of LBNP, blood samples were obtained to measure norepinephrine (NE), epinephrine (E), and atrial natriuretic peptide (ANP) levels. RESULTS: At baseline, CVP (12 +/- 5 and 16 +/- 7 mm Hg), heart rate (72 +/- 9 and 70 +/- 13 beats/min), cardiac index (2.3 +/- 0.6 and 2.5 +/- 0.9 L/min), NE (median, 341 pg/mL [range,198 to 789 pg/mL] and 365 pg/mL [range, 177 to 675 pg/mL] or 2.02 nmol/L [range, 1.17 to 4.66 nmol/L] and 2.16 nmol/L [range, 1.05 to 4.00 nmol/L]), E (median, 46 pg/mL [range, 18 to 339 pg/mL] and 58 pg/mL [range, 21 to 122 pg/mL] or 251 pmol/L [range, 98 to 1,951 pmol/L] and 317 pmol/L [range, 115 to 666 pmol/L]) were similar, whereas systolic arterial pressure (141 +/- 26 versus 164 +/- 22 mm Hg) and ANP (median, 441 pg/mL [range, 152 to 1,330 pg/mL] versus 804 pg/mL [range, 517 to 3,560 pg/mL] ng/L) were lower (P < 0.05) in HP patients. In response to LBNP (-40 mm Hg), CVP decreased by 6.5 +/- 4.0 mm Hg in the HP group and 4.9 +/- 4.9 mm Hg in the HR group. In HP patients, this decrease was associated with a greater decrease in SI (37% +/- 16% versus 27% +/- 16%) and systolic arterial pressure (19% +/- 21% versus 4% +/- 14%) than in HR patients. Plasma ANP levels did not change, whereas increases in NE and E levels were similar in HP and HR patients. CONCLUSION: Patients who frequently experience episodes of hypotension during dialysis also are prone to develop hypotension during LBNP, which results from reduced myocardial contractile reserve and/or inadequate sympathetic tone.

Aged↗
PubMed2003

Transfusion-associated graft vs. host disease after donor-specific leukocyte transfusion before kidney transplantation.

Transfusion-associated graft vs. host disease (TA-GVHD) is a well-known but rare complication that follows infusion of histo-incompatible lymphoid cells, often seen in individuals with impaired cellular immunity. However, we present here a case report of fatal TA-GVHD in a 'presumed' immunocompetent patient after transfusion of a freshly isolated buffycoat from a relative as part of our protocol to prepare the patient for living-related kidney transplantation. To confirm the diagnosis of TA-GVHD, a polymerase chain reaction was used to detect donor cells in various affected tissues. Furthermore, the immune reactivity of the patient against donor and vice versa was tested on samples taken before transfusion using limiting dilution assays. Our patient received a transfusion with blood from a donor who was homozygous at the human leukocyte antigen (HLA) class I loci. Despite incompatibility for HLA class II, infused donor T lymphocytes were not rejected and became engrafted. The patient did not have cytotoxic T lymphocytes to reject the donor cells. DNA polymorphism studies on several organ biopsies confirmed the presence of infiltrating cells of donor origin. This report illustrates the possibility, in the general patient population, of developing TA-GVHD from whole blood transfusion. In the case of pre-transplant blood transfusion, the patient and donor have to be HLA-typed and special care should be taken in the situation of donor homozygosity for HLA class I, even in the presence of HLA class II incompatibility. Protocols in which donor-specific blood or bone marrow transfusions are given in an attempt to modulate the immune system should exclude these combinations.

Adult↗
PubMed2003

Tacrolimus dose requirement in renal transplant recipients is significantly higher when used in combination with corticosteroids.

AIMS: To evaluate the effect of corticosteroids on tacrolimus pharmacokinetics. METHODS: In a randomized trial, kidney transplant recipients were treated with tacrolimus and mycophenolate mofetil with either daclizumab (n = 31) or 3 months of prednisone (n = 34). Tacrolimus dose-adjusted predose concentrations (C0) at month 1-6 were compared between both groups and within the corticosteroid group before and after prednisone withdrawal. RESULTS: At month 1 the tacrolimus dose-adjusted C0 in the corticosteroid group was 83 +/- 8 vs 119 +/- 17 ng ml-1 mg-1 kg-1 in the daclizumab group. The tacrolimus dose-adjusted C0 within the corticosteroid group at month 1 and 2 was 42% and 29% lower compared with month 4 (P < 0.001). CONCLUSIONS: A higher tacrolimus dose is required to reach target concentrations when used in combination with corticosteroids.

Adrenal Cortex Hormones↗
PubMed2003

Preload dependence of new Doppler techniques limits their utility for left ventricular diastolic function assessment in hemodialysis patients.

Left ventricular (LV) hypertrophy leads to diastolic dysfunction. Standard Doppler transmitral and pulmonary vein (PV) flow velocity measurements are preload dependent. New techniques such as mitral annulus velocity by Doppler tissue imaging (DTI) and LV inflow propagation velocity measured from color M-mode have been proposed as relatively preload-independent measurements of diastolic function. These parameters were studied before and after hemodialysis (HD) with ultrafiltration to test their potential advantage for LV diastolic function assessment in HD patients. Ten patients (seven with LV hypertrophy) underwent Doppler echocardiography 1 h before, 1 h after, and 1 d after HD. Early (E) and atrial (A) peak transmitral flow velocities, peak PV systolic (s) and diastolic (d) flow velocities, peak e and a mitral annulus velocities in DTI, and early diastolic LV flow propagation velocity (V(p)) were measured. In all patients, the E/A ratio after HD (0.54; 0.37 to 1.02) was lower (P < 0.01) than before HD (0.77; 0.60 to 1.34). E decreased (P < 0.01), whereas A did not. PV s/d after HD (2.15; 1.08 to 3.90) was higher (P < 0.01) than before HD (1.80; 1.25 to 2.68). Tissue e/a after HD (0.40; 0.26 to 0.96) was lower (P < 0.01) than before HD (0.56; 0.40 to 1.05). Tissue e decreased (P < 0.02), whereas a did not. V(p) after HD (30 cm/s; 16 to 47 cm/s) was lower (P < 0.01) than before HD (45 cm/s; 32 to 60 cm/s). Twenty-four hours after the initial measurements values for E/A (0.59; 0.37 to 1.23), PV s/d (1.85; 1.07 to 3.38), e/a (0.41; 0.27 to 1.06), and V(p) (28 cm/s; 23 to 33 cm/s) were similar as those taken 1 h after HD. It is concluded that, even when using the newer Doppler techniques DTI and color M-mode, pseudonormalization, which was due to volume overload before HD, resulted in underestimation of the degree of diastolic dysfunction. Therefore, the advantage of these techniques over conventional parameters for the assessment of LV diastolic function in HD patients is limited. Assessment of LV diastolic function should not be performed shortly before HD, and its time relation to HD is essential.

Adult↗
PubMed2003

Differential expression of heme oxygenase-1 and vascular endothelial growth factor in cadaveric and living donor kidneys after ischemia-reperfusion.

The extent of graft damage after ischemia-reperfusion reflects the balance between deleterious events and protective factors. Heme oxygenase-1 (HO-1) and vascular endothelial growth factor (VEGF) may contribute to cytoprotection by their anti-inflammatory and antiapoptotic properties. For investigating whether HO-1 and VEGF play a role in the adaptive response to ischemia-reperfusion injury after renal transplantation, kidney biopsies were analyzed from living (n = 45) and cadaveric (n = 16) donors, obtained at three time points: at the end of cold storage T(-1), after warm ischemia T(0), and after reperfusion T(+1). The mRNA expression levels of HO-1, VEGF(165), Bcl-2, Bax, and hypoxia inducible factor-1alpha were quantified by real-time reverse transcriptase-PCR, and the HO-1 and VEGF proteins were analyzed by immunohistochemistry. Cadaveric donor kidneys presented higher mRNA expression levels of hypoxia inducible factor-1alpha. In contrast, mRNA expression levels of HO-1, VEGF(165), and Bcl-2 were significantly lower in kidneys from cadaveric donors. Overall, a significant correlation was observed between mRNA expression of Bcl-2 and VEGF(165), between Bcl-2 and HO-1, and between HO-1 and VEGF(165). Moreover, protein expression of HO-1 and VEGF was detected in the same anatomical kidney compartments (glomerulus, arteries, and distal tubules). Renal function at the first week posttransplantation (analyzed by serum creatinine levels) showed a significant correlation with both HO-1 and VEGF mRNA expression, reinforcing the protective role of both genes in the early events of transplantation. It is concluded that the lower expression of HO-1, VEGF(165), and Bcl-2 in cadaveric donor kidneys can reflect a defective adaptation against ischemia-reperfusion injury that may affect their function in the short term.

Adult↗
PubMed2003

Living renal donors: optimizing the imaging strategy--decision- and cost-effectiveness analysis.

PURPOSE: To determine the most cost-effective strategy for preoperative imaging performed in potential living renal donors. MATERIALS AND METHODS: In a decision-analytic model, the societal cost-effectiveness of digital subtraction angiography (DSA), gadolinium-enhanced magnetic resonance (MR) angiography, contrast material-enhanced spiral computed tomographic (CT) angiography, and combinations of these imaging techniques was evaluated. Outcome measures included lifetime cost, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios. A base-case analysis was performed with a 40-year-old female donor and a 40-year-old female recipient. RESULTS: For the donor, MR angiography (24.05 QALYs and 9,000 dollars) dominated all strategies except for MR angiography with CT angiography, which had an incremental ratio of 245,000 dollars per QALY. For the recipient, DSA and DSA with MR angiography yielded similar results (10.46 QALYs and 179,000 dollars) and dominated all other strategies. When results for donor and recipient were combined, DSA dominated all other strategies (34.51 QALYs and 188,000 dollars). If DSA was associated with a 99% specificity or less for detection of renal disease, MR angiography with CT angiography was superior (34.47 QALYs and 190,000 dollars). CONCLUSION: For preoperative imaging in a potential renal donor, DSA is the most cost-effective strategy if it has a specificity greater than 99% for detection of renal disease; otherwise, MR angiography with CT angiography is the most cost-effective strategy.

Angiography, Digital Subtraction↗
PubMed2002

Differential intragraft cytokine messenger RNA profiles during rejection and repair of clinical heart transplants. A longitudinal study.

After clinical heart transplantation, ischemia, acute rejection, and repair mechanisms can trigger the up-regulation of cytokines. To investigate the cytokine profile early after transplantation, we monitored messenger RNA (mRNA) expression levels of tumor necrosis factor-alpha (TNF-alpha), monocyte chemoattractant protein-1 (MCP-1), transforming growth factor-beta (TGF-beta), platelet-derived growth factor-A (PDGF-A), and basic fibroblast growth factor (bFGF) by reverse transcriptase-polymerase chain reaction (RT-PCR) in serial endomyocardial biopsies ( n=123) from 16 cardiac allograft recipients during the first 3 post-operative months. In the first month, mRNA expression levels of MCP-1, TNF-alpha, TGF-beta, and bFGF were significantly higher than in the period thereafter (acute rejection episodes excluded). Acute rejection (International Society for Heart and Lung Transplantation (ISHLT) rejection grade >2) was strongly associated with the level of TNF-alpha mRNA. After acute rejection episodes, rising mRNA expression levels of PDGF-A and bFGF were found. The association between TNF-alpha mRNA and acute rejection reflects the importance of this cytokine in allogeneic responses. Elevated growth factor expression levels indicate repair responses after tissue damage due to either the transplantation procedure (surgery, ischemia, reperfusion) or acute allograft rejection.

Acute Disease↗
PubMed2002

Right-sided laparoscopic live-donor nephrectomy: is reluctance still justified?

BACKGROUND: Laparoscopic donor nephrectomy (LDN) of the right kidney is performed with great reluctance because of the shorter renal vein and possible increased incidence of venous thrombosis. METHODS: In this retrospective, clinical study, right LDN and left LDN were compared. Between December 1997 and May 2001, 101 LDN were performed. Seventy-three (72%) right LDN were compared with 28 (28%) left LDN for clinical characteristics, operative data, and graft function. RESULTS: There were no significant differences between the two groups regarding conversion rate, complications, hospital stay, thrombosis, graft function, and graft survival. Operating time was significantly shorter in the right LDN group (218 vs. 280 min). CONCLUSION: In this study, right LDN was not associated with a higher number of complications, conversions, or incidence of venous thrombosis compared with the left LDN. Thus, reluctance toward right LDN is not justified, and therefore, right LDN should not be avoided.

Humans↗
PubMed2002

Effect of HLA-DR matching on acute rejection after clinical heart transplantation might be influenced by an IL-2 gene polymorphism.

BACKGROUND: To examine whether genetic factors are involved in the development of acute rejection (AR), we investigated a (CA)m(CT)n repeat in the 3'-flanking region of the interleukin (IL)-2 gene. METHOD: We genotyped 290 heart transplant recipients with and without AR (International Society for Heart and Lung Transplantation criteria > or =3A) and 101 controls. RESULTS: The frequency of allele 135 of the repeat and its genotype distribution (carriers/noncarriers) were significantly associated with freedom from AR (P=0.03 and P=0.02, respectively). We also found interaction between allele 135 and HLA-DR matching. More carriers of allele 135 with no or one mismatch remained free from AR compared to patients without the allele (P=0.01). This was not found in the HLA-DR group with two mismatches. CONCLUSION: HLA-DR matching might only be effective in reducing AR after heart transplantation in recipients who carry allele 135 of the (CA)m(CT)n repeat in the 3'-flanking region of the IL-2 gene.

3' Untranslated Regions↗
PubMed2002

Antidiuretic hormone release during laparoscopic donor nephrectomy.

BACKGROUND: During laparoscopic procedures, increased intra-abdominal pressure may cause transient renal dysfunction due to impaired renal blood flow and induction of neurohormones. However, the relationship between antidiuretic hormone (ADH) secretion and increased intra-abdominal pressure is poorly understood. HYPOTHESIS: Laparoscopic donor nephrectomy (LDN) is associated with an increase in plasma ADH concentration, which influences renal function in both the donor and transplanted graft. OBJECTIVES: To evaluate plasma ADH levels during LDN and to correlate ADH levels with graft function. DESIGN AND INTERVENTIONS: In 30 patients who underwent LDN, plasma ADH levels were collected before insufflation, during surgery, after desufflation, and 24 hours after the procedure. In 6 patients who had open donor nephrectomy, blood samples were obtained as controls. Furthermore, graft function, operative characteristics, and clinical outcome were compared. SETTING: University hospital. RESULTS: In the LDN group, mean ADH levels during pneumoperitoneum and 30 minutes postinsufflation were significantly higher compared with preinsufflation values (P<.001). Twenty-four hours after LDN, mean ADH levels had returned to normal values. There were no significant differences in ADH levels in the open donor nephrectomy group. No significant differences in either intraoperative diuresis, blood pressure readings, or postoperative graft function were documented among the 2 groups. CONCLUSIONS: In this study, LDN was associated with an increase in plasma ADH that appeared to be related to increased intra-abdominal pressure. We conclude that the increased ADH concentrations during LDN are not associated with clinically significant changes in either the kidney donor or the transplanted graft.

Adult↗
PubMed2002

A broad and strong humoral immune response to donor HLA after implantation of cryopreserved human heart valve allografts.

Cryopreserved human heart valves are used for valve replacement in patients with congenital or acquired heart disease. Although no blood group or human leukocyte antigens (HLA) matching is performed and no immunosuppression is administered, the clinical results are relatively good. After valve replacement, the majority of the patients develop HLA antibodies, whereas a smaller group of patients shows valve-related events at the long term after right ventricular outflow tract reconstruction. Therefore, we hypothesized that not the mere presence, but rather the titers of antidonor HLA antibodies may be related to valve allograft failure. The presence and specificity of HLA class I antibodies were determined by complement-dependent microlymphocytotoxicity (CDC) test in longitudinally taken peripheral blood samples of 35 valve allograft recipients. In eight patients with an antibody response specific against donor-HLA class I, the titers were measured by this CDC method after stepwise dilution of the plasma. Panel reactive antibodies of more than 10% were found in 31 of 35 (89%) valve allograft recipients. From these 31 patients, 24 (77%) developed donor-specific HLA class I antibodies. All eight selected patients had detectable donor-specific antibody titers, ranging from 1:2 to 1:8,000. Two donor valve recipients before retransplantation had (donor-specific) HLA antibodies and showed high titers of 1:256 and 1:8,000 shortly after the second allograft valve replacement, which was associated with an early graft failure in the latter patient. We conclude that transplantation of cryopreserved human heart valve allografts leads to a broad and strong humoral response, which is probably the result of a lack of immunosuppressive therapy after valve transplantation. Patients receiving a second or following valve allograft appeared to be sensitized and developed early and high allo-antibody titers after second valve allograft implantation. Valve failure was diagnosed in a patient with extremely high titers. These findings suggest that preoperative cross-matching may identify patients with high donor-specific HLA antibody titers and may reduce the risk for early recurrent graft failure.

Adolescent↗
PubMed2002

Sequential monitoring of intragraft cytokine mRNA expression in relation to diastolic left ventricular wall thickness and function early after heart transplantation.

Because production of immune regulatory proteins may play a role in early graft dysfunction after heart transplantation, we analyzed whether intragraft cytokine messenger RNA (mRNA) expression levels are associated with diastolic left ventricular function in cardiac allografts. We intensively monitored 16 cardiac allograft recipients during the first 3 months after transplantation. The mRNA expression levels of tumor necrosis factor (TNF-alpha), monocyte chemoattractant protein-1 (MCP-1), transforming growth factor (TGF-beta), platelet derived growth factor (PDGF-A), and basic fibroblast growth factor (bFGF) were measured in endomyocardial biopsies (n = 123) by quantitative RT-PCR. To determine diastolic allograft function, concurrent M-mode and two-dimensional Doppler echocardiograms were analyzed for the following parameters: left ventricular total wall thickness, maximal early and atrial mitral flow velocity, deceleration time of maximal early mitral flow velocity, and isovolumetric relaxation period. During the first 3 months post-transplant an overall decrease in mRNA expression levels of almost all measured cytokines was observed, which paralleled an improvement in diastolic left ventricular wall thickness and function. However, no straightforward relationship could be found between a specific cytokine mRNA expression pattern and the studied echocardiographic parameters. Our data suggest that the improvement in diastolic left ventricular function is associated with a general reduction of inflammation within the allograft, rather than related to a specific cytokine expression pattern.

Adult↗
PubMed2002

Specific effect of the infusion of glucose on blood volume during haemodialysis.

BACKGROUND: Intradialytic morbid events such as hypotension and cramps during haemodialysis are generally treated by infusion of iso- or hypertonic solutions. However, differences may exist between solutions with respect to plasma refilling and vascular reactivity. METHODS: We compared the effect of no infusion (NI) with isovolumetric infusion of isotonic saline 0.9% (IS), saline 3% (HS), isotonic glucose 5% (IG), glucose 20% (HG) and mannitol 20% (HM), in six patients during the first hour of six standardized haemodialysis sessions with ultrafiltration. Relative blood volume was monitored continuously by measurement of the intravascular amount of protein. Blood pressure was measured by an oscillometric method, while cardiac output was measured by a thoracic impedance technique. RESULTS: At baseline, no differences in serum urea, sodium, potassium, glucose and osmolarity were found between the various infusion experiments. The maximum increase in relative blood volume directly after infusion was significantly greater with HG (5.1+/-0.7%) than with all other infusions (P<0.05). Stroke volume increased (21.0+/-19.2%, P<0.05) and total peripheral resistance decreased significantly (15.4+/-16.4%, P<0.05) after HG infusions. CONCLUSIONS: Infusion of hypertonic glucose during dialysis results in a greater increase in relative blood volume (RBV) than equal volumes of other solutions. As mannitol has the same osmolarity, molecule mass and charge, the greater increase in RBV following hypertonic glucose appears to be a specific effect, possibly related to a decline in vascular tone. It is therefore uncertain whether the observed increase in plasma volume during hypertonic glucose infusions will be of clinical benefit.

Adult↗