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Biomedical subjects

G J Becker

Publications and source records attributed to G J Becker.

At least 37 records · Page 2Linked to original sources
PubMed2000

Initial results of reteplase in the treatment of acute lower extremity arterial occlusions.

PURPOSE: To assess the feasibility and efficacy of reteplase in transcatheter arterial thrombolysis for lower extremity occlusive disease. MATERIALS AND METHODS: Fifteen consecutive patients with acute lower extremity ischemia due to occlusive disease were treated by means of catheter-directed thrombolysis with reteplase. Following diagnostic angiography, thrombolysis was started either from an antegrade puncture site in cases of femoropopliteal occlusions, or from the contralateral groin in cases of thrombosis of the iliac artery, common femoral artery, or infrainguinal bypass grafts. Reteplase was infused at a rate of either 0.5 U/h (six patients) or 1.0 U/h (nine patients). RESULTS: Complete thrombolysis was achieved in all of the nine (100%) patients in the 1.0 U/h group and in four of six (66%) patients in the 0.5 U/h group for a combined success rate of 13 of 15 (87%). Clinical success was achieved in 11 of 15 patients overall (73%). Major bleeding complications occurred in none of the 9 patients in the 1.0 U/h group and in one (16%) of the six patients in the 0.5 U/h group for an overall rate of 6%. CONCLUSIONS: Reteplase shows promise as an alternative to urokinase in the treatment of lower extremity ischemia due to arterial occlusive disease.

Acute Disease↗
PubMed2000

Influence of anti-rejection therapy on the timing of cytomegalovirus disease and other infections in renal transplant recipients.

Infections are an important cause of mortality and morbidity in renal transplant recipients. To study the impact of anti-rejection therapy on the timing of infections, the records of 599 consecutive renal transplants, performed prior to 31 December 1996 at the Royal Melbourne Hospital, were reviewed. Patients were grouped according to acute rejection (AR) episode and treatment during the first 6 months after transplantation. Group 1 [n = 168 (35%)] patients did not experience any episode of AR. Group 2 [n = 169 (35%)] patients had one or more episodes of AR and received high doses of steroids. Group 3 [n = 141 (30%)] patients had more than one episode of AR and received anti-lymphocyte antibodies in addition to high doses of steroids. Infections were more common in Groups 2 and 3 but only cytomegalovirus (CMV) disease occurred earlier in patients treated with lympholytics. Given the high incidence and early onset of CMV disease in patients receiving lympholytics and considering that an effective prophylactic protocol remains undetermined, pre-emptive treatment with ganciclovir in this high risk group appears justified.

Acute Disease↗
PubMed2000

Ischemic acute renal failure: long-term histology of cell and matrix changes in the rat.

BACKGROUND: The cellular infiltration and matrix accumulation accompanying acute renal ischemia and reperfusion have been frequently noted but poorly defined. The long-term consequences of ischemia may irreversibly damage the kidney. METHODS: Female Sprague-Dawley rats (200 g) underwent unilateral nephrectomy. After five days, the left renal pedicle was occluded for 45 minutes. Animals were sacrificed at 0, 1, 2, 4, 8, 16, 32, 64, and 180 days postischemia (N = 6). Immunohistochemistry for monocytes/macrophages (Mo/Mphi, ED-1), myofibroblasts [alpha-smooth muscle actin (alpha-SMA)], collagen III and IV, matrix metalloproteinase-2 (MMP-2) and proliferating cell nuclear antigen (PCNA) and terminal dUTP nick end labeling (TUNEL) were performed. RESULTS: Kidney weights of postischemic animals were increased at all time points (postischemic to controls, 1.47 +/- 0.21 to 0.94 +/- 0.12 g at day 8; 1.49 +/- 0.20 to 1.27 +/- 0.13 g at day 64; and 1.86 +/- 0.1 to 1. 24 +/- 0.2 g at day 180). Serum creatinine values increased to 0.42 +/- 0.10 mmol/L at day 2 but returned to control levels by day 8 (0. 05 mmol/L). Glomerular collagen IV was decreased from 2 to 16 days postischemia, which was accompanied by an increase in MMP-2. The fractional area of the interstitium was greatest at day 8 (19.55 +/- 0.91% compared with day 0 at 8.08 +/- 0.27%), with a second increase observed at day 180 (16.61 +/- 0.70%). Interstitial Mo/Mphi increased postischemia from days 2 through 8 (8.84 +/- 2.12 to 133. 32 +/- 14.04 per 0.91 mm2) and then decreased. Myofibroblasts proliferated locally (PCNA double labeling was demonstrated), and increased numbers were found from days 2 through 16 (maximal at day 8, 26.96 +/- 3.04%, compared with day 0, 0.88 +/- 0.11%). In the postischemic groups, collagen IV increased to day 8 (20.84 +/- 1. 30%), but then decreased to below control values at day 64 (2.22 +/- 0.15%) before returning to normal by day 180. Interstitial collagen III increased to 8 days (0.45 +/- 0.07% to 2.55 +/- 0.36%) and then decreased to control levels by day 32, but showed a marked increase to approximately 6% at days 64 and 180. Cellular proliferation (PCNA) was maximal at days 2 and 4 (affecting tubule cells and myofibroblasts but not macrophages). Apoptosis was maximal at day 8 (in both interstitial and tubule cells) in the postischemic groups. CONCLUSION: Marked changes in the accumulation of Mo/Mphi, MF, and collagen IV were found in this model of ischemic acute renal failure. The reversibility of functional and structural changes is in marked contrast to that found in progressive disease. The increases observed for collagen III at 64 and 180 days postischemia suggest that in the long term, however, further chronic structural changes may be observed.

Acute Kidney Injury↗
PubMed2000

Human renal fibroblast contraction of collagen I lattices is an integrin-mediated process.

BACKGROUND: Expression of the beta1 family of integrins allows dermal fibroblasts in wounds to contribute to the healing process through migration, adhesion, synthesis, and rearrangement of extracellular matrix. To date the ability of human renal fibroblasts to reorganize collagens and the role of cell surface receptors in this process remain unknown. METHODS: Renal fibroblasts were grown from the cortical tissue of surgically removed human kidneys. The ability of human renal fibroblasts to reorganize interstitial collagen I was examined in vitro using solidified collagen I lattices. Integrin function was blocked by incubating fibroblasts with isotype-specific antibodies prior to addition to collagen I lattices. RESULTS: Human renal fibroblasts embedded in collagen I lattices progressively decreased lattice diameter to 60.6+/-11.4% of initial diameter at 48 h post-release (P:<0.01). Fibroblasts incubated in the presence of antibody to beta1 integrin failed to contract collagen I lattices, whilst fibroblasts incubated with non-specific antibody reduced lattice diameter to 60.1+/-12.4% of initial diameter at 48 h post-release (P:<0.01). Further characterization of integrin alpha subunits showed that blocking alpha2beta1 integrin prevented lattice contraction (P:<0.05, alpha2beta1 integrin antibody vs non-specific antibody), whilst blocking of alpha5beta1, alpha3beta1 and alpha1beta1 integrins did not influence this process. CONCLUSIONS: We postulate that collagen I fibril rearrangement by human renal fibroblasts in vitro appears to be an integrin-mediated process involving the alpha2beta1 integrin.

Adult↗
PubMed2000

Effects of haemoglobin normalization on quality of life and cardiovascular parameters in end-stage renal failure.

BACKGROUND: The optimal haemoglobin concentration ([Hb]) for patients with end-stage renal failure is uncertain. In particular, it is unclear whether Hb normalization may be an advantage to such patients who are otherwise well. METHODS: A prospective, randomized, double-blind cross-over study was completed in 14 haemodialysis patients (12 male) aged between 23 and 65 years over a period of 18 months, using a variety of measures to examine the effect of epoetin at target [Hb] of 10 g/dl ([Hb](10)) and 14 g/dl ([Hb](14)). Patients were randomized to maintain one or other of the target levels for 6 weeks before being crossed over to the alternative [Hb]. Baseline data (mean [Hb]: 8.5+/-0.2 g/dl) were also included selectively. Six patients were known to be hypertensive. Comparisons were made between 24-h ambulatory blood pressure levels (ABP), echocardiographic findings and estimates of blood volume (BV), plasma volume (PV) and Hb mass. Quality of life estimates were obtained using the Sickness Impact Profile (SIP), and epoetin dosage requirements at target [Hb] were assessed. RESULTS: Daytime and nocturnal ABP (systolic and diastolic) were not different at the respective target [Hb], although nocturnal diastolic levels were higher compared with baseline (73+/-4 mmHg) at both [Hb](10) (83+/-3, P:<0.01) and [Hb](14) (81+/-6, P:<0.05). Significant reductions in cardiac output (5.2+/-0.3 vs 6.6+/-0.5 l/min, P:<0.01) and left ventricular end-diastolic diameter (4.8+/-0.2 vs 5.2+/-0.2 cm, P:<0. 001) were found at [Hb](14) compared with [Hb](10). Left ventricular mass index was correlated with both PV (P:<0.001) and BV (P:<0.01), but not with Hb mass. The PV decreased as the [Hb] rose (P:<0.001) but BV remained unchanged. Quality of life was significantly improved at [Hb](14) compared with [Hb](10) for both total score (6. 5+/-1.7 vs 13.4+/-3.0, P:=0.01) and psychosocial dimension score (5. 4+/-1.9 vs 15.4+/-4.0, P:<0.01). The maintenance weekly dose of epoetin required was 80% higher at [Hb](14) compared with [Hb](10) (P:<0.001). CONCLUSION: These data suggest there may be a significant haemodynamic and symptomatic advantage in maintaining a physiological [Hb] in haemodialysis patients. Although untoward effects were not identified in this study at [Hb](14), a substantially higher dose of epoetin is required to maintain this level.

Adult↗
PubMed2000

The role of tubulointerstitial injury in chronic renal failure.

Progressive renal failure results from a triad of glomerulosclerosis, tubulointerstitial fibrosis and vascular sclerosis. The mechanisms by which tubules are injured, and by which the tubular epithelial cell then excites interstitial inflammation culminating in fibroblast activation and fibrosis have become increasingly understood. Most current methods to prevent progressive glomerulosclerosis would inherently prevent tubular injury and interstitial fibrosis. The behaviour and control of the renal fibroblast is being investigated, with the potential for direct interference with its functions.

Disease Progression↗
PubMed2000

Peripheral arterial obstruction: prospective study of treatment with a transluminally placed self-expanding stent-graft. International Trial Study Group.

PURPOSE: To evaluate the safety and efficacy of an endoluminal prosthesis for treatment of peripheral arterial occlusive disease (PAOD). MATERIALS AND METHODS: A self-expanding endoprosthesis with an expanded polytetrafluoroethylene tube inside a nitinol support structure was implanted in 127 patients with symptomatic PAOD in the iliac (61 limbs) and femoral arteries (80 limbs). Clinical category status, ankle-brachial index, and color duplex flow imaging results were recorded before treatment, at discharge, and at 1, 3, 6, and 12 months after treatment. Aspirin was administered throughout the study, and heparin was administered during and for 2 days after the procedure. RESULTS: Endoprosthesis deployment was technically successful in all patients. Complications occurred in 24 of 141 procedures and included three major complications. Early thrombosis (within 30 days) occurred in one iliac and three femoral arteries. Late restenosis or reocclusion was observed in five iliac and 14 femoral arteries within the 1st year. Primary patency rates in iliac arteries were 98% +/- 3% (standard error) and 91% +/- 4%, respectively, at 6 and 12 months after treatment. Primary patency rates in femoral arteries were 90% +/- 3% and 79% +/- 5%, respectively, at 6 and 12 months. Secondary patency rates were 95% and 93% for iliac and femoral arteries, respectively, at 12 months after treatment. CONCLUSION: The device used in this study can be implanted without additional risks to the patient and provided encouraging patency rates up to 1 year.

Adult↗
PubMed2000

Heroin overdose and myoglobinuric acute renal failure.

BACKGROUND: Heroin abuse is an increasing problem in Australia. In our hospitals we have noted an apparent increase in drug-related admissions. In this study we aimed to examine the incidence of renal failure due to heroin-related rhabdomyolysis and to determine any predisposing factors to the requirement for dialysis in these patients. PATIENTS AND METHODS: We identified a group of 27 patients who developed renal failure after recent intravenous heroin use. There was a significant rise in the incidence during 1997-1998 compared with the previous seven years (p < 0.05). RESULTS: Rhabdomyolysis was the likely cause of renal failure in all cases. Eight patients required dialysis for an average of 14 days (range 3-26). Patients who required dialysis had a higher admission creatine kinase (115 x 10(3) U/l (1-316), median (range), versus 9 x 10(3) (0-91 ), p < 0.05 ), a higher admission creatinine (3.8 mg/dl (2.1- 6.7) versus 2.4 (1.4-8.1), p < 0.05 ), a higher peak creatinine kinase (129 x 10(3) U/l (2-316) versus 22 x 10(3) (3-197), p < 0.05), a lower urine output in the initial 24 hours (0.91/24 hrs (0.1-1.5) versus 3.9(1.0-11.1), p < 0.005) and a longer length of hospitalization (37 days (17-112) versus 12 (5-87), p < 0.05). No patient died and all patients had independent renal function at last review. The majority of patients had significant comorbidities. The incidence of serological evidence of exposure to blood-borne viruses was HIV 5% (n = 1), hepatitis B 10% (n = 2) and hepatitis C 74% (n = 17) of patients tested. Pneumonia occurred in 52% (n = 14) and 26% (n = 7) developed respiratory failure requiring intubation. 22% (n = 6) developed a compartment syndrome requiring fasciotomy and 37% (n = 10) had significant residual limb weakness at discharge. CONCLUSION: There is an increase in patients admitted with rhabdomyolysis-induced renal failure associated with heroin use in our hospitals. We found a varied approach to an increasing clinical problem and suggest that a consistent investigative and therapeutic approach be introduced. Although renal recovery can be expected, long-term disability may occur due to potential serious complications.

Acute Kidney Injury↗
PubMed1999

Impact of acute rejection therapy on infections and malignancies in renal transplant recipients.

BACKGROUND: Infections and malignancies are important causes of mortality and morbidity in renal allograft recipients. Their risk increases with increasing immunosuppression. METHODS: In an attempt to quantitate the increase in the risk of these complications in association with antirejection therapy, we reviewed the records of all renal allograft recipients of our center transplanted during the cyclosporin era. We sub-divided the patients into three groups based on acute rejection episodes during the first 6 months posttransplant, and the treatment for acute rejection: those who did not develop AR--group 1 (n=168); those who had one or more episodes of acute rejection and were treated with high dose corticosteroids --group 2 (n=169); those who in addition to corticosteroids required cytolytics (OKT3) and/or other drugs--group 3 (n=141). RESULTS: 52% patients in group 1, 71% patients in group 2 and 86% patients in group 3 had one or more episodes of infection during the first 6 months posttransplantation. Relative risk for group 2 and 3 were 1.56 (P=0.0002) and 2.98 (P<0.00001), respectively. Infection/patient rates at 6 months were 0.67, 1.23, and 2.79 in groups 1, 2, and 3 respectively. Groups 1 and 2 had a similar number of cases with squamous and basal cell carcinoma, however, there were few cases with these malignancies in group 3. No case of lymphoma was seen in group 1; there were four cases in group 2 and nine in group 3. There was no significant difference in patient survival in group 1 and 2, however, patients in group 3 had a reduced patient survival (1 vs. 3 P<0.001, 2 vs. 3 P=0.067). Graft survival was best in group 1 and worst in group 3 (1 vs. 2 P<0.05; 1 vs. 3 P<0.00001; 2 vs. 3 P<0.01). CONCLUSIONS: In renal transplant recipients the risk of infections and lymphoma increases with increasing immunosuppression and hence mortality and morbidity associated with it. When adding a potent immunosuppressive agent to rescue a kidney one needs to consider the serious and at times fatal side effects given the modest beneficial effect on long-term outcome.

Acute Disease↗
PubMed1999

May-Thurner syndrome in an adolescent: persistence despite operative management.

We describe a patient with May-Thurner syndrome who underwent operative transection and transposition of the right common iliac artery without direct venous repair, because preoperative and intraoperative intravascular ultrasound scans were negative for "spurs" in the left common iliac vein. When symptoms and signs persisted, a postoperative magnetic resonance venogram (MRV) showed severe stenosis in the left common iliac vein. Progressive, but incomplete, clinical improvement occurred with conservative management.

Adolescent↗
PubMed1999

Macrophage and myofibroblast involvement in ischemic acute renal failure is attenuated by endothelin receptor antagonists.

BACKGROUND: Endothelin (ET) may be a mediator of injury following ischemia-induced acute renal failure (ARF). ET receptor (ETR) antagonists have been reported to increase survival rates and lower serum creatinines when administered postrenal ischemia-reperfusion injury in the rat. Renal cellular and extracellular matrix responses to this therapy have not been addressed. METHODS: We investigated the use of ETR antagonists, PD 156707 (ETA) and SB 209670 (ETA and ETB) in the treatment of sublethal postischemic ARF. The right kidney of female Sprague-Dawley rats weighing approximately 200 g was removed. After five days, the left renal pedicle was occluded for 45 minutes. Twenty-four hours after renal ischemia, one of two ETR antagonists, PD 156707 (N = 7) or SB 209670 (N = 8), was administered. Experimental animals were compared with an ischemic group receiving only saline (N = 9). Three nephrectomized groups that did not undergo ischemia but that received infusions of saline (N = 6), PD 156707 (N = 6), and SB 209670 (N = 6), respectively, were also studied. Animals were sacrificed one week postischemia. Quantitation of monocytes and macrophages (Mo/Mphi), alpha-smooth muscle actin-positive myofibroblasts, and collagens type III and IV was performed by immunohistochemical staining. Cell kinetics were examined by staining for apoptosis with terminal deoxyuridine triphosphate (dUTP) nick end labeling and for proliferation with proliferating cell nuclear antigen. RESULTS: All ischemic groups of rats initially developed raised serum creatinine levels; however, no significant difference was observed between the groups (Kruskal-Wallis). Creatinines returned to preischemic values in all groups by the time of sacrifice. No significant difference in kidney weights or body weights was found between groups. Histologically, infiltration of Mo/Mphi was significantly reduced in groups treated with ETR antagonists (P < 0.001). The presence of myofibroblasts was also significantly reduced in the antagonist-treated groups (P < 0. 001). This was also paralleled by reduced quantities of collagen IV in the treated rat groups (P < 0.001). The interstitial area was also significantly greater in the saline group (P < 0.001). The amount of collagen III did not significantly differ between rat groups. Apoptosis was reduced (P < 0.001) by treatment with ETR antagonists, whereas proliferation was enhanced (P < 0.005). All non-ischemic groups showed no variation in any parameter studied at this time point. CONCLUSIONS: Treatment of ischemic ARF in the rat with ETR antagonists PD 156707 and SB 209670 attenuated cellular infiltration and matrix accumulation. An advantage of one antagonist over the other could not be determined in this study. The marked discrepancy between function and pathology (former unchanged, latter markedly improved) may be due to the time frame of this experiment, and longer outcome measures need to be assessed.

Actins↗
PubMed1999

Tissue factor pathway inhibitor expression in human crescentic glomerulonephritis.

BACKGROUND: Tissue factor (TF) pathway inhibitor (TFPI), the major endogenous inhibitor of extrinsic coagulation pathway activation, protects renal function in experimental crescentic glomerulonephritis (GN). Its glomerular expression and relationship to TF expression and fibrin deposition in human crescentic GN have not been reported. METHODS: Glomerular TFPI, TF, and fibrin-related antigen (FRA) expression were correlated in renal biopsies from 11 patients with crescentic GN. Biopsies from 11 patients with thin basement membrane disease and two normal kidneys were used as controls. RESULTS: TFPI was undetectable in control glomeruli but was detectable in interstitial microvessels. In crescentic biopsies, TFPI was detected in cellular crescents and was more prominent in fibrous/fibrocellular crescents, indicating a correlation with the chronicity of crescentic lesions. TFPI appeared to be associated with macrophages but not endothelial or epithelial cells. TFPI was generally undetectable in regions of the glomerular tuft with minimal damage. In contrast, TF and FRA were strongly expressed in regions of minimal injury, as well as in more advanced proliferative and necrotizing lesions. Despite prominent TF expression, FRA was less prominent in fibrous/fibrocellular crescents in which TFPI expression was maximal. CONCLUSIONS: These data suggest that TFPI is strongly expressed in the later stages of crescent formation and is inversely correlated with the presence of FRA in human crescentic GN. This late induction of TFPI may inhibit TF activity and favor reduced fibrin deposition in the chronic stages of crescent formation.

Adult↗
PubMed1999

Renal myofibroblasts contract collagen I matrix lattices in vitro.

Myofibroblasts, cells with both fibroblastic and smooth muscle cell features, have been implicated in renal scarring. In addition to synthetic properties, contractile features and integrin expression may allow myofibroblasts to rearrange and contract interstitial collagenous proteins. Myofibroblasts from normal rat kidneys were grown in cell-populated collagen lattices to measure cell generated contraction. Following detachment of cell populated collagen lattices, myofibroblasts progressively contracted collagen lattices, reducing lattice diameter by 42% at 24 h. Alignment of myofibroblasts, rearrangement of fibrils and beta(1) integrin expression were observed within lattices. We postulate that interstitial myofibroblasts contribute to renal scarring through manipulation of collagenous proteins.

Animals↗
PubMed1999

Response to parathyroidectomy at the axial and appendicular skeleton in renal patients.

AIM AND METHODS: We report increases in axial and appendicular bone density after parathyroidectomy in renal patients. Bone density was recorded pre-operatively and at 6 weeks, 6 months and 1 year post-operatively. We have previously reported that axial bone density increased dramatically at 6 weeks but that there were no early cohort increases at the appendicular skeleton [Stein et al. 1997]. RESULTS: We now report that at six months, bone density had continued to increase at the lumbar spine and femoral neck, with median respective 6 months increases over baseline of 1.3 (p < 0.01) and 0.7 (p < 0.01 ) Z-scores. Bone density then appeared to stabilize at the axial skeleton. At the appendicular skeleton increases were significant at the one year time point with median respective increases at the ultradistal radius and one third radius of 0.46 (p < 0.05) and 0.49 (p < 0.05) Z-scores. The different pattern of responses to parathyroidectomy between the axial and appendicular sites supports the concept that appendicular bone turnover is slower than axial bone turnover. Furthermore, at the appendicular skeleton, bone turnover appears similar between cortical and trabecular bone. CONCLUSION: In renal patients, bone density increases after parathyroidectomy at both the axial and appendicular skeleton. Axial increases are large and occur early. Appendicular increases occur at both cortical and trabecular sites but are slower than the axial changes.

Absorptiometry, Photon↗
PubMed1998

Stent grafts for aortic aneurysms: the next interventional challenge.

Stent grafts (endografts) have proved useful for the endoluminal exclusion of peripheral and aortic aneurysms, both those in native arteries and those resulting from prior surgery. In addition, their use may apply in some patients with occlusive vascular disease. Various types of endografts are being evaluated in clinical trials, including those that utilize unsupported grafts with stentlike attachment mechanisms and those having a metallic endoskeleton or exoskeleton. Relatively complex devices can be delivered through small arteriotomies and in some cases percutaneous approaches. Unsupported grafts, although more prone to kinking and incomplete expansion, appear to work well. Some devices employ modularity, which involves separate placement of contralateral limbs and, in some cases, extension devices. For performing endovascular grafting, pretreatment planning is critical and requires sophisticated imaging, including spiral computed tomography (CT) with 3-dimensional reconstruction and angiographic evaluation using catheters with calibrated markers. Potential advantages of endovascular grafts include a decreased hospital stay, a less invasive procedure, and lower morbidity and mortality. Several issues remain unresolved and should be addressed by the newer generation of these devices.

Animals↗