Iodine-131-metaiodobenzylguanidine dosimetry in cancer therapy: risk versus benefit

In the treatment of neural crest tumors, such as pheochromocytoma, with[131I]MIBG, bone marrow toxicity limits the amount of administered activity and, thus, a therapeutically useful tumor dose. METHODS: We calculated tumor doses in a series of diagnostic studies with [123I]MIBG using accurate quantification of SPECT and planar scintigraphy. By extrapolating diagnostic results to therapeutic activities of [131I]MIBG, we could compare the results with whole-body doses from a series of therapies. RESULTS: The tumor dose was DT = 2.2 mGy MBq(-1) (median value of 27 measurements, range 0.04 < or = DT < or = 20 mGy MBq(-1) and the whole-body dose in a series of 16 patients undergoing 50 therapies was DWB = 0.12 +/- 0.04 mGy MBq(-1) (mean +/- s.d.). The therapeutic ratio varied between 130 to below 10 in some patients. CONCLUSION: The results were compared with published data. We found clearly skewed distribution of tumor doses, with a majority of tumors receiving only a few mGy per MBq administered activity. In some patients, however, doses did reach 20 mGy MBq(-1).     

Local mobility within villin 14T probed via heteronuclear relaxation measurements and a reduced spectral density mapping

Villin 14T, a representative domain from the actin severing and bundling protein villin, binds calcium ions and actin monomers. To begin to understand the contributions of mobility to the villin-calcium and villin-actin interactions, relaxation rates for magnetization involving the amide nitrogens and protons have been measured for 15N-labeled villin 14T in solution. Although we have measured the complete set of rates required for a full spectral density map, difficulties in the accurate measurement of relaxation rates for antiphase coherence and two-spin order led us to consider a reduced mapping formalism. From the reduced spectral density map, a model-free analysis, or directly from the measured Nx,y relaxation rates, local variations in mobility along the backbone of villin 14T have been revealed. Fast motions are evident not only at the amino and carboxyl termini but also in the turn between strands beta 4 and beta 5 of the central beta-sheet and in the turn between helix alpha 3 and strand beta 7. Slower motions are suggested for the turn between strands beta 2 and beta 3. Motions on the microsecond to millisecond time scale have been probed directly by examining the dependence of the proton transverse relaxation rate on the spin-locking field strength. Leu11 shows a strong dependence on field strength, implying conformational exchange with a time constant of 125 +/- 69 microseconds. The backbone at the actin-binding interface appears to be rather rigid.     

Acute erythroleukemia: evaluation of 48 cases with reference to classification, cell proliferation, cytogenetics, and prognosis

We evaluated 48 archival cases of acute erythroleukemia and divided them into 3 groups: M6a, corresponding to the traditional French-American-British M6 category; M6b, which is pure erythroleukemia; and M6c, in which myeloblasts and pronormoblasts each account for more than 30% of cells by the French-American-British exclusion criteria. No significant differences were noted among the subtypes for ratio of males to females; age; or exposure to toxins, alcohol, or both. However, compared with the patients in the M6a group, patients in the M6b and M6c groups demonstrated a statistically significant increase in cytogenetic aberrations, proliferation markers (proliferating cell nuclear antigen and Ki67), and ringed (type III) sideroblasts. Marked survival differences were noted between the M6a (30.1 +/- 29.5 months) and M6b (3.15 +/- 4.2 months) groups, with patients in the M6c group demonstrating an intermediate prognosis (10.5 +/- 12.7 months). Chemotherapeutic regimens induced remission in all treated patients in the M6a and M6c groups but did not appear to affect the M6b group. However, the patients in the M6c group remained in remission for a significantly shorter period of time than did patients in the M6a group. Overall, survival appeared to depend on the ratio of pronormoblasts to myeloblasts at diagnosis and demonstrated a rapid decline with increasing pronormoblast and decreasing myeloblast counts. We must, therefore, devise chemotherapeutic regimens that target both blastic components of this disease.     

Research bronchoscopies do not adversely affect HIV-infected individuals' future health-care decisions

STUDY OBJECTIVES: Asymptomatic HIV-infected individuals are increasingly recruited for studies involving invasive procedures such as bronchoscopy. We sought to determine the response to and outcome of a request for a research bronchoscopy in HIV-positive individuals with no respiratory disease, and whether this would adversely affect future decisions to have a medically indicated bronchoscopy. DESIGN AND SETTING: Prospective, semistructured, questionnaire-based study in a London teaching hospital HIV outpatient clinic. PARTICIPANTS: One hundred and seven consecutive HIV-infected eligible individuals. Thirty-one healthy volunteers served as a control group for the subjective response to bronchoscopy. MAIN OUTCOME MEASURES: Subjects' attitudes and responses to requests for bronchoscopy and subsequent behavior when they required medically indicated bronchoscopy. RESULTS: Seventy-five patients (70%) agreed to the procedure in principle, predominantly for altruistic reasons. Thirty-nine subjects underwent bronchoscopy. Five percent found it worse than expected; and 79% agreed to another research bronchoscopy (performed in 11 subjects approximately 2 years later). All patients said they would undergo bronchoscopy again for diagnostic purposes (required in seven during the study). When compared to a healthy volunteer population within the same study, postbronchoscopy symptoms were similar in frequency although somewhat different in nature. Subjects felt that a clear explanation of what was involved enhanced their participation in this research. CONCLUSIONS: Invasive research procedures such as bronchoscopy can be performed and are repeatable in a healthy HIV-infected population. Performance of procedures for research purposes does not appear to adversely affect future health-care decisions.     

Articular cartilage volume in the knee: semiautomated determination from three-dimensional reformations of MR images

PURPOSE: To determine the accuracy of semiautomated quantification of articular cartilage volume from three-dimensional (3D) reformations of magnetic resonance (MR) images. MATERIALS AND METHODS: Sagittal, fat-suppressed, 3D, spoiled gradient-recalled-echo MR imaging of two bovine and two human cadaver knees was performed. Articular cartilage volume was calculated from 3D reformations of the MR images by using a semiautomated program written at the authors' institution. Calculated volumes were compared with directly measured volumes of the surgically removed articular cartilage. RESULTS: The percentage of error of the MR imaging-determined volumes was 6.53% +/- 4.75 (mean +/- standard deviation). A strong correlation between the two sets of observations was shown (r=.997). Linear regression showed the calculated volumes to be highly accurate (slope=1.002, P>.25). Repeated reformations yielded volumes that were reproducible (mean absolute error, 0.013 mL +/- 0.019) and not significantly different from the measured volume (P>.10). CONCLUSION: Semiautomated quantification of knee articular cartilage from MR images yields highly accurate cartilage volumes.     

Screening for diabetic retinopathy: the utility of nonmydriatic retinal photography in Egyptian adults

BACKGROUND AND OBJECTIVE: Drug resistance has become a major cause of treatment failure in patients with acute leukemia. P-glycoprotein (Pgp), which is associated with the multidrug resistance (MDR) phenotype, has been reported to be an important predictor of treatment outcome. The aim of this study was to analyze the value of Pgp expression in bone marrow or peripheral blood as a predictor of the response to remission induction chemotherapy as well as the duration of remission in patients with de novo acute myeloid leukemia (AML). DESIGN AND METHODS: We examined the expression of Pgp in 82 patients with de novo AML using an immunocytochemical assay with the C219 monoclonal antibody. RESULTS: Twenty-seven of the 82 patients (33%) were C219-positive in from 1% to 100% of their cells. Thirteen cases (16%) showed a positive reaction in more than 50% of the leukemic cells. Only hyperleukocytosis was significantly associated with higher expression of Pgp. Although 8 of the 13 cases (62%) with more than 50% of cells having Pgp expression were CD34-positive, this association was not statistically significant. A univariate analysis of resistance to induction therapy showed a significantly higher resistance rate in patients with increased Pgp expression (P = 0.01) as well as in those patients with decreased reactivity to myeloperoxidase. The multivariate analysis revealed the independent prognostic value of Pgp expression. C219 reactivity did not have an influence on remission duration. INTERPRETATION AND CONCLUSIONS: Our data indicate that P-glycoprotein expression is a reliable marker of resistance to induction treatment in patients with de novo AML.     

Inter-individual variability in Ca2+ signalling in platelets from healthy volunteers: effects of aspirin and relationship with expression of endomembrane Ca2+-ATPases

Increased Ca2+ signal generation may lead to hyperactivity of platelets and contribute to thrombotic complications. Using fura-2-loaded platelets from 51 healthy volunteers, high variability was detected in the Ca2+ responses evoked by the receptor agonists, thrombin and collagen, and the inhibitor of sarco/endoplasmic reticulum Ca2+-ATPases (SERCA), thapsigargin (Tg). Oral intake of 500mg aspirin reduced the magnitude of the Ca2+ responses, and lowered the intra-individual coefficients of variance of the responses by 50%. However, the corresponding inter-individual variance coefficients were only a little influenced by aspirin intake, pointing to subject-dependent factors in Ca2+ handling that are unrelated to thromboxane formation. With each agonist, 6-9% of the subjects had platelets with relatively high Ca2+ responses (> mean + SD) both before and after aspirin intake. In 90% (9/10) of these cases the high responsiveness was confirmed in platelets obtained 6-12 months later. The Tg- but not thrombin-induced Ca2+ responses correlated inversely with the expression levels of SERCA PL/IM 430 (SERCA-3b) in platelets. After aspirin intake, the Ca2+ responses with collagen but not thrombin correlated inversely with SERCA-2b expression. These results suggest that, in the absence of potentiating effects of thromboxane, (i) the amount of PL/IM 430-recognizable SERCA may control the Ca2+ signal when SERCA-2b is specifically inhibited (with Tg), and (ii) the expression of SERCA-2b determine the collagen- but not the thrombin-evoked Ca2+ signal. Accordingly, limited Ca2+-pumping activity by low expression of one of the SERCA isoforms is likely to be one of the factors resulting in increased platelet activity towards collagen or thapsigargin but not thrombin.     

High-output congestive heart failure following transjugular intrahepatic portal-systemic shunting

A hyperdynamic circulatory state with elevated cardiac output, decreased peripheral vascular resistance, and sodium retention occurs in patients with portal cirrhosis. Surgical portal-systemic shunts and transjugular intrahepatic portal-systemic shunts (TIPS) have been shown to worsen the high-output state in these patients. However, clinical evidence of high-output congestive heart failure has been reported only rarely to complicate cirrhosis. We describe a patient who developed high-output congestive heart failure with markedly elevated filling pressures after TIPS and had complete resolution of heart failure after liver transplantation.     

信息管理系统中的工作流技术研究与设计

介绍了工作流的应用背景,分析了某校教务系统中采用的工作流技术的原理和设计思想。提出可编辑、管理和监控的工作流模型,并重点介绍了工作流程运行机制。工作流技术使单位内部业务流程自动化,信息流转逐步实现无纸化。利用其图形化定义流程的功能,在办公流程越来越严谨的前提下,办公效率也大幅提高。某校在教务系统中运用了工作流技术,取得了良好的效果。