Reduced complications during hemodialysis by automatic blood volume controlled ultrafiltration.

BACKGROUND: Intradialytic morbid events (IMEs, mostly hypotension) are frequent complications during hemodialysis (HD). This study investigated whether automatic feedback control via adjustment of the ultrafiltration rate reduces IME frequency. METHODS: In this multi-center cross-over study, 56 hypotension-prone patients were treated both with standard HD (sHD, applying a constant ultrafiltration rate) and HD applying a blood volume controlled ultrafiltration rate (cHD). The relative blood volume (RBV) was continuously monitored. The individual relative blood volume limit (RBVcrit ) was determined from the measured RBV during initial sHD. During cHD, the ultrafiltration rate was automatically adjusted to keep the actual RBV above RBVcrit. RESULTS: In 3,081 HD treatments, slightly fewer IMEs were observed during cHD than during sHD (0.785+/-0.613 versus 0.695+/-0.547 per treatment, P=0.144). Less symptomatic events were seen during cHD: -13% for symptomatic hypotension (0.594 versus 0.685 per treatment, P=0.120), and -32% for cramps (0.049 versus 0.072 per treatment, P=0.009). Thirty-one patients with the highest IME rate (IME in at least every second treatment) especially benefited from cHD: 1.185+/-0.554 versus 0.979+/-0.543 IME per treatment (P=0.004). The reduction in blood pressure (BP) and the increase in heart rate were lower during the treatments with cHD than with sHD: systolic BP: -18.8+/-26.7 versus -22.2+/-28.9 mmHg (P=0.007), diastolic BP: -7.8+/-14.8 versus -9.1+/-15.3 mmHg (P=0.064), heart rate: 1.8+/-10.4 versus 2.3+/-11.6 per minute (P=0.014). Neither treatment duration nor ultrafiltration volume was significantly different between cHD and sHD. CONCLUSION: For cHD, less intradialytic morbid events were observed than for sHD, and pre- to post-dialytic changes in blood pressure and heart rate were less pronounced.

Dosimetric evaluation of a new collimator insert system for stereotactic radiotherapy.

The prototype of a stereotactic collimator set developed in our department is evaluated for clinical use. This set consists of three cylindrical blocks mounted on a tray which slides in the wedge insert of a Siemens Primus accelerator. Each block has a collimating hole along its long axis to produce radiation fields of circular cross-section at the isocentre plane with diameters of 15 mm, 20 mm and 25 mm. Different geometric and dosimetric quality assurance tests were performed and results are found within the limits set for stereotactic radiotherapy. Dosimetry results measured using Kodak EDR-2 radiographic film and a pinpoint ion chamber also show good agreement with corresponding results calculated by Monte Carlo simulation of the linear accelerator head and the collimators. Measured dosimetry data were used to adapt a conventional PLATO treatment planning system for stereotactic radiotherapy using the prototype collimator set. Treatment planning system calculations and film measurements for treatment of an intracranial lesion in an anthropomorphic head phantom using coplanar 180 degrees arcs are compared and found to agree within 2 mm. This supports the accuracy of dose delivery using the prototype stereotactic collimators. Despite their increased penumbra (2.5-3.5 mm relative to 2-2.5 mm for commercially available collimators) the ease of construction makes the proposed stereotactic collimators an interesting alternative for accomplishing cost effective stereotactic treatments.

Dose verification of single shot gamma knife applications using VIPAR polymer gel and MRI.

This work describes an experimental procedure with potential to assess the overall accuracy associated with gamma knife clinical applications, from patient imaging and dosimetry planning to patient positioning and dose delivery using the automated positioning system of a Leksell Gamma Knife model C. The VIPAR polymer gel-MRI dosimetry method is employed due to its inherent three-dimensional feature and linear dose response over the range of gamma knife applications. Different polymer gel vials were irradiated with single shot gamma knife treatment plans using each of the four available collimator helmets to deliver a maximum dose of 30 Gy. Percentage relative dose results are presented not only in the form of one-dimensional profiles but also planar isocontours and isosurfaces in three dimensions. Experimental results are compared with corresponding Gammaplan treatment planning system calculations as well as acceptance test radiochromic film measurements. A good agreement, within the experimental uncertainty, is observed between measured and expected dose distributions. This experimental uncertainty is of the order of one imaging pixel in the MRI gel readout session (<1 mm) and allows for the verification of single shot gamma knife applications in terms of acceptance specifications for precision in beam alignment and accuracy. Averaging net R(2) results in the dose plateau of the 4 mm and 18 mm collimator irradiated gel vials, which were MR scanned in the same session, provides a crude estimate of the 4 mm output factor which agrees within errors with the default value of 0.870.

Detailed kinetic study of the thermoluminescence glow curve of synthetic quartz.

A detailed kinetic analysis has been performed of the thermoluminescence (TL) glow curve of high purity synthetic quartz. The kinetic parameters of the glow peak at 110 degrees C were evaluated for doses ranging from 0.1 Gy to 100 Gy using glow curve deconvolution (GCD), initial rise, variable heating ratc and phosphorescence decay methods. All the methods gave results that agree within the experimental errors.

Search for common characteristics in the glow curves of quartz of various origins.

The thermoluminescence (TL) glow curves of quartz of various origins were measured under two different conditions, (1) unannealed samples and (2) samples annealed at 500 degrees C and 900 degrees C. The different glow curves obtained were analysed using first order kinetics and glow curve deconvolution (GCD) analysis. The comparison of the glow curves obtained was mainly concentrated in studying the sensitivities of the glow peaks as a function of the annealing temperature, and in obtaining the kinetic parameters of the glow peak at '110 degrees C'. Furthermore, in four samples the detailed comparison was extended to the trapping parameters of all existing glow peaks. It was found that despite their different origin and the different shapes of the glow curves, there are several basic characteristics that are common to all samples studied.

Glomerular and tubular proteinuria as markers of nephropathy in rheumatoid arthritis.

OBJECTIVE: We examined the prevalence of nephropathy in unselected patients with rheumatoid arthritis (RA) by measurement of marker proteins for glomerular and tubular damage in urine. METHODS: A highly sensitive immunoluminometric assay was used to measure albumin, immunoglobulin G and alpha1-microglobulin in 24 h urines of 44 RA patients and a control group of 46 patients with generalized osteoarthritis (OA). RESULTS: Fifty-five per cent of RA patients were found to have proteinuria as a symptom of renal disease. Drug therapy or vasculitis were identified as possible reasons for proteinuria in only 25% of these patients; in most patients (75%), no reason for proteinuria was found. Tubular and mixed proteinuria were more frequent than glomerular proteinuria. Only 15% of the control group exhibited mild proteinuria, which was attributable to nephrotoxic factors. The renal function of RA patients and the control group did not differ significantly. CONCLUSIONS: Proteinuria is a frequent symptom of nephropathy in RA. Screening for renal disease in RA should not only include creatinine measurement and dipstick examination of urine, but also more sensitive methods to detect tubular and glomerular proteinuria as a marker of tubular and early stages of glomerular damage.

Wegener's granulomatosis associated with renal cell carcinoma.

OBJECTIVE: To determine the frequencies and types of malignant neoplasms occurring before or simultaneously with the diagnosis of Wegener's granulomatosis (WG), and to test for the presence of "Wegener's autoantigen," proteinase 3 (PR3), in malignant tissues from WG patients to ascertain whether an association exists between malignancy and WG. METHODS: A retrospective statistical analysis was performed on the medical records of 477 patients with WG as compared with a control group of 479 patients with rheumatoid arthritis (RA). A murine monoclonal antibody was used to test malignant tissues for the presence of PR3. RESULTS: A malignant neoplasm was found in 23 patients in the WG group and in 18 patients in the control group. The odds ratio for malignant neoplasm in the WG group was 1.79 (P = 0.0876, 95% confidence interval [95% CI] 0.92-3.48). Seven patients with renal cell carcinoma were found in the WG group compared with 1 patient in the control group, for an odds ratio of 8.73 (P = 0.0464, 95% CI 1.04-73.69). Simultaneous occurrence of cancer and WG was observed in 14 patients with WG compared with 1 control patient, for an odds ratio of 18.00 (P = 0.0059, 95% CI 230-140.67). Furthermore, the diseases occurred simultaneously in 5 of the 7 patients with both WG and renal cell carcinoma, but not in the single patient in the control group with RA and renal cell carcinoma. PR3 could not be detected in any of the 8 malignant tissue samples (4 renal cell carcinomas) investigated in the patients from the WG group. CONCLUSION: The close temporal association between renal cell carcinoma and WG suggests that malignancy is, in some cases, a trigger for the development of WG. However, since PR3 was not found in malignant tissues from the WG patients, the immunopathologic mechanisms leading to autoimmunity and vasculitis remain unclear.

Interferon-alpha treatment of four patients with the Churg-Strauss syndrome.

BACKGROUND: Interferon-alpha is reported to have a beneficial effect on patients with the idiopathic hypereosinophilic syndrome. OBJECTIVE: To study the effect of interferon-alpha on the Churg-Strauss syndrome. DESIGN: Case series. SETTING: University hospital. PATIENTS: Four patients with biopsy-proven Churg-Strauss syndrome. INTERVENTION: Interferon-alpha at dosages of 7.5 to 63 million U per week. MEASUREMENTS: Disease extent, disease activity, and blood eosinophil count in a treatment period ranging from 14 to 25 months. RESULTS: Interferon-alpha therapy led to remission of disease and a substantial reduction of the prednisolone requirement in two patients who had attained incomplete remission with cyclophosphamide or methotrexate. The third patient's condition stabilized, and the fourth patient maintained remission. During interferon-alpha therapy, the blood eosinophil count in all patients decreased in a dose-dependent manner and paralleled the extent of clinical disease and disease activity. CONCLUSIONS: Interferon-alpha may be an effective treatment for the Churg-Strauss syndrome. It seems to exert its effect primarily by producing a dose-dependent decrease in the blood eosinophil count.

High plasma levels of the soluble form of CD30 activation molecule reflect disease activity in patients with Wegener's granulomatosis.

PURPOSE: To determine the plasma levels of soluble CD30 (sCD30) in Wegener's granulomatosis (WG) patients, and to investigate the possible correlation of sCD30 with disease extent and activity. PATIENTS AND METHODS: sCD30 was determined by radioimmunoassay in 57 WG patients, 25 patients with rheumatoid arthritis (RA), 23 patients with bacterial infections and 21 healthy controls (HC). The extent and activity of WG disease were assayed according to disease extent index (DEI) and standard laboratory parameters. RESULTS: Plasma sCD30 levels in generalized WG (22.5 +/- 1.5 U/mL), but not in initial phase WG (12.1 +/- 4.0 U/mL), were significantly increased compared with HC (8.8 +/- 0.9 U/mL, P < 0.0001). Furthermore, of 11 generalized WG patients who received long-term follow-up, sCD30 levels declined when the disease activity changed from active disease to remission (29.1 +/- 1.9 U/mL to 15.9 +/- 1.8 U/mL, P = 0.0001). Similar results were observed in the whole group of generalized WG, eg, sCD30 levels in active disease (29.4 +/- 1.4 U/mL) were significantly higher than in partial remission (17.9 +/- 1.9 U/mL, P < 0.001) and in complete remission (13.7 +/- 3.3 U/mL, P < 0.001). No significant difference was noted between complete remission and HC. In addition, sCD30 levels were correlated with other parameters of disease extent and activity such as DEI, plasma levels of sIL-2R, PR3-ANCA, ESR and CRP. The sCD30 levels were increased in RA patients compared with HC (15.2 +/- 2.1 U/mL, P < 0.05), but no correlation was found between disease activity parameters and sCD30 levels. In contrast, in patients with bacterial infections sCD30 levels (6.9 +/- 0.9 U/mL) were not significantly different compared with HC. CONCLUSION: Plasma levels of sCD30 are not only significantly increased but also correlate with disease extent and activity in generalized WG. These findings suggest that sCD30 can act as a useful marker for evaluation of disease extent and activity, and that generalized WG may be associated with Th2-type immune response.

Polymorphisms in the tumor necrosis factor genes in Wegener's granulomatosis.

Two known di-allelic polymorphisms in the tumor necrosis factor (TNF) genes were investigated in 35 patients suffering from Wegener's granulomatosis (WG) in comparison to 111 healthy controls. The first polymorphism lay in the promotor region of the TNF-alpha gene at position -308, the second in the first intron of the TNF-beta gene. For both polymorphisms we could not find any statistically significant differences in allele frequencies between patients and healthy individuals. In the patient group the TNF 2/2 phenotype was slightly elevated, however (WG 5.7% vs. normal 1.8%). Investigating the clinical course of the disease according to TNF polymorphisms, TNF 1/1 patients were found to have a higher mean disease extension index (DEI) than TNF 1/2 individuals (TNF 1/1 10.5 vs. TNF 1/2 9.4).

Therapy for the maintenance of remission in sixty-five patients with generalized Wegener's granulomatosis. Methotrexate versus trimethoprim/sulfamethoxazole.

OBJECTIVE: To compare the efficacy of low-dose intravenous (IV) methotrexate (MTX; 0.3 mg/kg once weekly), both with and without concomitant prednisone, versus daily oral trimethoprim/sulfamethoxazole (T/S; 160 mg of trimethoprim + 800 mg of sulfamethoxazole twice a day), with and without prednisone, in maintaining remission in patients with generalized Wegener's granulomatosis (WG). METHODS: In this study, 65 patients with generalized WG whose disease had entered remission with cyclophosphamide (CYC) and prednisone therapy were started on one of the following remission-maintenance regimens: MTX alone (group A; n = 22), T/S alone (group B; n = 24), MTX plus concomitant prednisone (group C; n = 11), and T/S plus concomitant prednisone (group D; n = 8). Clinical, radiographic, and seroimmunologic data were evaluated to assess the efficacy of the 4 regimens and to seek possible predictive factors concerning outcome in each group. RESULTS: Partial or complete remission was maintained in 86% of the patients in group A, but in only 58% of those in group B (P < 0.05). In group C, 91% of patients remained in remission, which is in sharp contrast to group D, in which all patients experienced a relapse after a median of 14.5 months (P < 0.005). Side effects occurred twice as often with MTX (n = 12) as with T/S (n = 6) treatment and could usually be resolved by supplemental folinic acid. Two patients taking MTX and 3 patients taking T/S were withdrawn from the study medication because of side effects. In none of the patients were the adverse effects life threatening. No statistically significant factors predictive of poor outcome emerged in any group. CONCLUSION: Low-dose MTX was found to be superior to T/S for the safe and effective maintenance of remission in patients with generalized WG. The use of concomitant prednisone was not associated with a worse outcome with MTX treatment. Since T/S, especially with concomitant prednisone, seemed to increase the chance of relapse, neither T/S alone nor T/S plus prednisone can be recommended for the maintenance of remission in patients with generalized WG.

[ANCA-associated vasculitis (Wegener's granulomatosis, Churg-Strauss syndrome, microscopic polyangiitis). 3. Therapeutic procedure]. / ANCA-assoziierte Vaskulitiden (Wegener-Granulomatose, Churg-Strauss-Syndrom, Mikroskopische Polyangiitis). 3. Therapeutisches Procedere.

Recent studies on the long-term clinical course of ANCA-associated vasculitides have revealed considerable variation in the clinical severity of the disease. The most effective standard therapy (i.e., daily cyclophosphamide + prednisolone, "FAUCI-scheme") is associated with high treatment-related morbidity and mortality as well as a high incidence of relapse. On the other hand, less toxic therapeutic strategies (e.g., monthly bolus of cyclophosphamide or weekly low-dose methotrexate) are being pursued with remarkable success in non-life threatening disease. Intractable cases (under daily cyclophosphamide + prednisolone) may profit from additional high dose IVIG therapy or from monoclonal antibodies against CD4 and CDw52 molecules. Plasmapheresis can be effective in combination with the standard therapy in dialysis patients with necrotizing glomerulonephritis (in Wegener's granulomatosis or microscopic polyarteritis). On the other hand, Wegener's granulomatosis restricted to the upper and/or lower respiratory tract ("Initial WG") responds to trimethoprimsulfamethoxazole. In future, therefore, an individualized strategy adapted to extension and activity has to be developed for the treatment of each patient with ANCA-associated vasculitis.

Rapid angiographic progression of coronary artery disease in patients with elevated lipoprotein(a)

BACKGROUND: The mechanisms underlying rapid angiographic progression of coronary artery disease are still unknown. Intravascular thrombosis with or without plaque rupture may be involved. METHODS AND RESULTS: In a prospective study in 79 patients with coronary artery disease and at least one coronary diameter stenosis > or = 50%, possible risk factors for rapid progression were investigated. Quantitative coronary angiography was performed twice at a mean time interval of 66 +/- 25 days. Rapid progression of coronary disease defined as (1) an increase > 10% in stenosis severity in at least one stenosis > or = 50%, (2) occurrence of a new stenosis > or = 50%, or (3) occlusion of a formerly patent vessel was found in 21 patients (27%). Between patients with rapid progression and those without, there were no significant differences in sex distribution, age, smoking history, frequency of hypertension or diabetes mellitus, and serum LDL cholesterol, HDL cholesterol, and apolipoprotein B concentrations. In contrast, serum lipoprotein(a) [Lp(a)] concentrations > or = 25 mg/dL were found in 14 of 21 patients (67%) with rapid progression of coronary artery disease but in only 19 of 58 (33%) in the group without progression (P = .007). The respective median Lp(a) concentrations were 66 mg/dL (range, 2 to 139) and 13 mg/dL (range, 2 to 211; P = .01). CONCLUSIONS: Lp(a) appears to be a risk factor for the rapid angiographic progression of coronary artery disease. The pathophysiological link between Lp(a) and rapid progression may be an interference with thrombolysis through the partial structural homology of Lp(a) with plasminogen.