Monte Carlo calculations of electron beam output factors for a medical linear accelerator

The purpose of this study was to investigate the application of the Monte Carlo technique to the calculation and analysis of output factors for electron beams used in radiotherapy. The code EGS4/BEAM was used to obtain phase-space files for 6, 12 and 20 MeV clinical electron beams from a scattering-foil linac (Varian Clinac 2100C) for a clinically representative range of applicator and square or rectangular insert combinations. The source-to-surface distance used was 100 cm. The field sizes ranged from 1 x 1 cm2 to 20 x 20 cm2. These phase-space files were analysed to study the intrinsic beam characteristics and used as source input for relative dose and output factor computations in homogeneous water phantoms using the code EGS4/DOSXYZ. The calculated relative central-axis depth-dose and transverse dose profiles at various depths of clinical interest agreed with the corresponding measured dose profiles to within 2% of the maximum dose. Calculated output factors for the fields studied agreed with measured output factors to about 2%. This demonstrated that for the Varian Clinac 2100C linear accelerator, electron beam dose calculations in homogeneous water phantoms can be performed accurately at the 2% level using Monte Carlo simulations.     

A study comparing mycophenolate mofetil to azathioprine in simultaneous pancreas-kidney transplantation

BACKGROUND: Mycophenolate mofetil (MMF; Cell-Cept) is a potent and selective inhibitor of B and T lymphocyte proliferation that has proven effective in reducing the incidence of acute rejection in cadaveric kidney transplant recipients in several randomized, blinded clinical studies. Because the frequency and characteristics of rejection episodes may be different and more severe after combined pancreas-kidney transplantation, we hypothesized that MMF would have a significant impact on pancreas-kidney rejection and graft outcome. Therefore, we compared the efficacy of MMF versus azathioprine (AZA) in cyclosporine-treated simultaneous pancreas-kidney transplantations. METHODS: A retrospective comparison of 358 consecutive primary SPK transplantations performed from 1990 to 1997 was conducted. Patients received either MMF (n=109, 3 g/day) or AZA (n=249, 2 mg/kg q.d.) in combination with cyclosporine-based immunosuppression. All patients received a quadruple-drug sequential induction protocol with either OKT3 or Atgam. Several outcome parameters, including patient and graft survival rates and frequency of rejection, were analyzed. RESULTS: MMF-treated patients demonstrated a markedly reduced rate of biopsy-proven kidney rejection (31 vs. 75% AZA, P=0.0001), clinically significant pancreas rejection (7 vs. 24% AZA; P=0.003), and steroid-refractory rejection (15 vs. 52% AZA; P=0.01). As a result, kidney and pancreas allograft survival was significantly better in MMF patients compared with AZA patients (2-year survival rates: kidney, 95 vs. 86%; and pancreas, 95 vs. 83%). Although surgical infections after transplantation were more frequent in MMF patients, MMF patients were more likely to have undergone enteric drainage. Importantly, we did not observe an increased incidence of any of the bacterial, fungal, or viral infections that typically plague immunosuppressed transplant recipients. CONCLUSIONS: This retrospective study demonstrates that MMF is a highly effective immunosuppressant in SPK transplantation. It is not associated with an increased risk of opportunistic infections when a balanced immunosuppressive management approach is used. MMF strikingly reduces the frequency of acute cellular and steroid-resistant rejection. As a result of this combined experience, it is not unexpected then that we observe significantly improved graft survival rates in MMF-treated SPK patients compared with patients receiving a more traditional immunosuppressive regimen.     

The patient from receiver of information to informed decision-maker

In this article the change of paradigm currently taking place within the field of patient education is indicated. In this change of paradigm the patient is increasingly being seen as responsible for his own health and as someone who makes independent choices in this respect. This has consequences for the role the patient is given in decisions on individuals care. The consequences of current developments within the Dutch society and in medical techniques as these relate to the need for patient education are enlightened. Some of the main topics for patient education are mentioned and the effects of patient education as established through meta-analyses are summarised. A planning model for a systematic development of patient education interventions is recommended. Relevant topics for research on patient education in the Netherlands are indicated.     

Multiple states of beta-sheet peptide protegrin in lipid bilayers

Protegrin-1 (PG-1), a beta-sheet antimicrobial peptide, was studied in aligned lipid bilayers by oriented circular dichroism (OCD). All of its spectra measured in a variety of lipid compositions were linear superpositions of two primary basis spectra, indicating that PG-1 existed in two different states in membranes. We designated these as state S and state I. The state assumed by PG-1 was strongly influenced by lipid composition, peptide concentration, and hydration condition. We have previously reported that the helical peptides, alamethicin and magainin, also exhibit two distinct OCD basis spectra-one corresponding to surface adsorption with the helix parallel to the bilayer and the other with perpendicular transbilayer insertion. States S and I of PG-1 may correspond to the surface state and the insertion state of alamethicin, since they show a similar dependence on lipid composition, peptide concentration, and hydration condition. Nonoriented CD spectra obtained from vesicle, micelle, and solution preparations are not linear superpositions of the basis spectra of the states S and I. This indicates that a molecular orientation change alone is insufficient to describe the S left and right arrow I transition. Rather, a more complicated process is taking place, perhaps involving a change in the hydrogen bonding pattern of the backbone. Although the structural basis of the OCD spectra remains to be determined, the discovery of two distinct states can provide information about dynamic changes of PG-1 in membranelike environments, properties undoubtedly related to its antimicrobial and cytotoxic effects.     

A multicenter trial of 6-aminocaproic acid (Amicar) in the prevention of bleeding in infants on ECMO

BACKGROUND/PURPOSE: Intracranial hemorrhage (ICH), is a major source of morbidity and the leading cause of death in neonates treated with extracorporeal membrane oxygenation (ECMO). Anecdotal reports have suggested that epsilon-aminocaproic acid (EACA) can decrease the risk of ICH. The purpose of this study was to evaluate, in a multiinstitutional, prospective, randomized, blinded fashion, the effect of EACA on the incidence of hemorrhagic complications in neonates receiving ECMO. METHODS: All neonates (except congenital diaphragmatic hernia) who met criteria for ECMO at three institutions were eligible for enrollment. EACA (100 mg/kg) or placebo was given at the time of cannulation followed by 25 mg/kg/h for 72 hours. Bleeding complications, transfusion requirements, and thrombotic complications were recorded. Post-ECMO imaging included head ultrasound scan computed tomography (CT) scan, and duplex ultrasound scan of the inferior vena cava and renal vessels. RESULTS: Twenty-nine neonates were enrolled (EACA, 13 and placebo, 16). Five (17.2%) patients had a significant (grade 3 or larger) ICH. There was no statistical difference in the incidence of significant ICH in patients who received EACA (23%) versus placebo (12.5%). Septic patients accounted for all of the ICH in the EACA group. Thrombotic complications (aortic thrombus and SVC syndrome) developed in two patients from the placebo group. There was no difference in thrombotic circuit complications between groups. CONCLUSIONS: Our results suggest that the use of EACA in neonates receiving ECMO is safe but may not decrease the overall incidence of hemorrhagic complications.     

Electrophysiological aids in distinguishing organic from psychogenic tremor

The clinical differentiation of tremors of organic and psychogenic origin can be difficult. We describe a patient with unilateral upper limb tremor that was initially considered to have a psychogenic cause, but subsequent frequency analysis of EMG signals and accelerometer recordings indicated that the tremor was organic in nature. An ischemic lesion in the contralateral lentiform nucleus found on MRI supported this conclusion. Quantitative electrophysiologic studies may thus be useful in distinguishing organic from psychogenic tremor.     

Ilarviruses encode a Cucumovirus-like 2b gene that is absent in other genera within the Bromoviridae

We found that RNA 2 of the four ilarviruses sequenced to date encodes an additional conserved open reading frame (ORF), 2b, that overlaps the 3' end of the previously known ORF, 2a. A novel RNA species of 851 nucleotides was found to accumulate to high levels in plants infected with spinach latent virus (SpLV). Further analysis showed that RNA 4A is a subgenomic RNA of RNA 2 and encodes all of ORF 2b. Moreover, a protein species of the size expected for SpLV ORF 2b was translated in vitro from the RNA 4A-containing virion RNAs. The data support the suggestion that the SpLV 2b protein is translated in vivo. The 2b gene of ilarviruses, which is not encoded by alfamoviruses and bromoviruses, shares several features with the previously reported cucumovirus 2b gene; however, their encoded proteins share no detectable sequence similarities. The evolutionary origin of the 2b gene is discussed.     

A new parameter for measuring metastatic bone involvement by prostate cancer: the Bone Scan Index

In this report, we describe a method for quantitative bone scan interpretation (the Bone Scan Index or BSI) in advanced prostate cancer. The BSI estimates the fraction of the skeleton that is involved by tumor, as well as the regional distribution of the metastases in the bones. The purpose of this report is to describe the development and validation of this method in terms of reproducibility and the application of BSI for determining extent of disease and monitoring disease progression. We analyzed 263 bone scans from 90 patients being studied under four protocols at Memorial Sloan-Kettering Cancer Center for progressive, androgen-independent prostate cancer (AIPC), who had bone scans as a part of their work-up. We determined: (a) the intraobserver and interobserver variability of the BSI; (b) the comparison between a change in BSI and prostate-specific antigen (PSA); (c) the regional distribution of bony metastases in early stage D prostate cancer (<3% skeletal involvement); and (d) the rate of growth of bony metastases from prostate cancer. A cube root transformation of the percentage of involvement of the entire skeleton was used to stabilize the variance over the entire span of values (0-60% tumor involvement). The range of interobserver variability between readers was 0.2-0.5 times the cube root of the BSI (69 scans, 18 patients). Intraobserver variability was minimal when the same reader read the same scans after a 2-year interval, showing a correlation coefficient of 0.97 (reader 1) and 0.99 (reader 2), P < 0.001. There was a parallel rise in the BSI and the PSA in 24 patients (105 scans) treated for AIPC with hydrocortisone followed by suramin at PSA relapse (Pearson's moment correlation, 0.71). In a group of 27 patients with limited bone involvement by AIPC (i.e., <3% BSI), the distribution of early metastases was not random within the skeleton but was distributed in the central skeleton in a manner that matched the distribution of the normal adult bone marrow. Also, in a group of 21 patients (62 scans), the change in BSI as a function of time after diagnosis was explored graphically. The progression of bone scan changes in AIPC, from early involvement (<3%) to late involvement, was fitted to a Gompertzian equation. It showed a rapid exponential growth phase, with an estimated tumor doubling time of 43 days when the BSI was 3.3%. The change in BSI rapidly approached a more gradual slope as the percentage of skeletal involvement increased. The BSI provides a reproducible new parameter for quantitative assessment of bone involvement by AIPC. These results suggest that the BSI will be useful for stratifying patients entering treatment protocols for extent of tumor involvement of bone. Although further study is necessary, serial bone scan BSI appears capable of quantifying both the progression of bony involvement by tumor as well as the response to treatment.     

Inhibition of glycohydrolase enzymes by aqueous extracts of Chinese medicinal herbs in a microplate format

A microplate assay, for use with a variety of glycohydrolase enzymes, was developed to aid the screening of Chinese medicinal herb extracts for the presence of potential anti-viral and anti-lymphoma compounds. The microplate assay method described offers greater convenience, speed and reproducibility over existing methods. The enzymes tested were alpha-glucosidase, beta-glucosidase and beta-glucuronidase. The assay can be easily adapted for use with other glycohydrolase enzymes. Of the 12 herb extracts examined four did not inhibit any of the enzymes (< 50% inhibition), one inhibited alpha-glucosidase only (> 50% inhibition), six inhibited beta-glucuronidase only, and one inhibited both alpha-glucosidase and beta-glucuronidase. None of the extracts were capable of inhibiting beta-glucosidase to any significant extent.     

Regional dynamic signal changes during controlled hyperventilation assessed with blood oxygen level-dependent functional MR imaging

PURPOSE: To quantitate the amplitude changes and temporal dynamics of regional functional MR imaging signals during voluntary hyperventilation using blood oxygen level-dependent contrast echo-planar imaging. METHODS: Seven male subjects were studied during voluntary hyperventilation (PetCO2 = 20 mm Hg) regulated by capnometry. Measurements were made on multisection echo-planar MR images obtained with parameters of 1000/66 (repetition time/echo time), flip angle of 30 degrees, and voxel size of 3 x 3 x 5 mm3. Sensitivity of the functional MR imaging signal to changes in PetCO2, time delays in relation to PetCO2 changes, and time constants of functional MR imaging signal changes were assessed on a region-by-region basis. RESULTS: Within 20 seconds of starting hyperventilation, rapid and substantial decreases in the functional MR imaging signal (by as much as 10%) were measured in areas of gray matter, which were significantly greater than the modest changes observed in white matter. Regional-specific effects in areas of the frontal, occipital, and parietooccipital cortex were stronger than in subcortical regions or in the cerebellum. Signal decreases measured with functional MR imaging were significantly delayed with respect to the reduction in PetCO2. Apparent differences between regional time constants did not reach statistical significance. CONCLUSION: Regional and gray-white matter differences in functional MR imaging signal changes during controlled hyperventilation may reflect differences in metabolic activity, vascular regulation, and/or capillary density. When measuring brain activation with functional MR imaging, arterial PCO2 differences due to unregulated respiration may confound interpretation of activation-related functional MR imaging signal changes.