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Controlled and uniform assembly of "bottom-up" nanowire (NW) materials with high scalability presents one of the significant bottleneck challenges facing the integration of nanowires for electronic applications. Here, we demonstrate wafer-scale assembly of highly ordered, dense, and regular arrays of NWs with high uniformity and reproducibility through a simple contact printing process. The assembled NW pitch is shown to be readily modulated through the surface chemical treatment of the receiver substrate, with the highest density approaching approximately 8 NW/mum, approximately 95% directional alignment, and wafer-scale uniformity. Such fine control in the assembly is attained by applying a lubricant during the contact printing process which significantly minimizes the NW-NW mechanical interactions, therefore enabling well-controlled transfer of nanowires through surface chemical binding interactions. Furthermore, we demonstrate that our printing approach enables large-scale integration of NW arrays for various device structures on both rigid silicon and flexible plastic substrates, with a controlled semiconductor channel width ranging from a single NW ( approximately 10 nm) up to approximately 250 microm, consisting of a parallel array of over 1250 NWs and delivering over 1 mA of ON current.

Allogeneic stem-cell transplantation (SCT) is potentially curative treatment for AML and MDS. New conditioning regimens are continuously explored trying to reduce toxicity while maintaining antileukemia effect. Treosulfan is an alkylating agent with in vitro cytotoxicity against leukemia as well as myeloablative and immunosuppressive properties when used in escalated doses. We explored a regimen of fludarabine (30 mg/m(2) x 5) and treosulfan (12 gr/m(2) x 3) in 24 patients, median age 55 years (range, 30-69), with AML (n = 19) or MDS (n = 5), not eligible for standard myeloablation. Donors were HLA-matched siblings (n = 11) or matched-unrelated (n = 13). Twenty-one patients engrafted within a median of 15 days. Extramedullary toxicity was relatively limited. The incidence of acute and chronic GVHD was 15% and 47%, respectively. With median follow-up of 19 months (range, 8 - 34), 16 patients are alive and 8 died (relapse-2, treatment-related-6). Two-year disease-free survival rate was 60% (95% CI, 39-81). The cumulative incidence of relapse was only 15% (95% CI, 5 - 44) while nonrelapse mortality rate was 25% (95% CI, 13-50). The fludarabine/treosulfan regimen can be considered a fully intensive, modified myeloablative regimen with effective antileukemia activity and acceptable toxicity in patients with AML/MDS not eligible for standard myeloablation, and merits further study in larger scale studies.

Reduced-intensity conditioning (RIC) regimens are increasingly used in allogeneic stem-cell transplantation (SCT). There are no data whether any of these regimens has advantage and in what setting. We retrospectively analyzed SCT outcomes in 151 patients given fludarabine-based RIC for various hematological malignancies; 72 conditioned with fludarabine and intravenous-busulfan (FB) and 79 with fludarabine and melphalan (FM). FM was more myelosuppressive. Grade III-IV organ toxicity occurred in 31 and 53% of FB and FM recipients (P=0.005) and acute graft-versus-host disease grade II-IV in 33 and 53%, respectively (P=0.01). Non-relapse mortality rate (NRM) was 16 and 40%, respectively (P=0.003). Active disease (HR 2.2, P=0.003) and prior autologous SCT (HR 1.7, P=0.04) predicted inferior overall survival (OS). Among patients transplanted in remission, OS was 72 and 36% after FB and FM, respectively (P=0.03) due to increased NRM with FM. Similarly, patients transplanted in active disease experienced higher NRM with FM, however lower relapse rates resulted in equivalent OS. In conclusion, there are marked differences in outcome between RIC regimens that are theoretically dose-equivalent. The FM regimen is more myelosuppressive and toxic but controls disease better. FB was associated with improved survival in patients transplanted in remission. These observations merit further study in prospective studies.

A generic approach for deploying various types of synthetic nanomaterials, including single-walled carbon nanotubes and nanoparticles, at well-defined locations on substrates is presented. The assembly is achieved through the complementary design of the stationary and carrier phases and utilizes the dewetting process during which polymer-encapsulated nanomaterials are delivered and positioned on predefined locations of substrates. Covalent modification of the nano-objects is not required for the building block positioning, therefore, preserving their intrinsic chemical and physical properties. The potency of this new approach is demonstrated for various synthetic nanomaterials, such as polystyrene, silica, and gold nanoparticles as well as single-walled carbon nanotubes, showing highly specific and direct patterning of cm2 areas using a generic assembly strategy.

Unlabelled: Little is known about the interaction of novel anticancer drugs with other treatment modalities. THE AIM of this study was to examine the effect of combining imatinib mesylate (STI-571) with radiation or cisplatin on the survival of two human solid tumor cell lines - SKNMC cells derived from Ewing sarcoma and breast cancer MCF-7 cells., Methods: Cell proliferation was determined using the sulphorodamine B cytotoxicity assay. Cell cycle analysis was performed with flow cytometry. Apoptosis was determined using a commercial cell death ELISA plus kit. Phosphorylated AKT, which has been suggested to be involved in radiation resistance, was detected by Western blot analysis., Results: Exposure of SKNMC cells to STI-571 resulted in a dose-dependent antiproliferative effect and a decrease in phosphorylated AKT expression. There was no evidence of apoptosis. The combination of STI-571 with radiation or cisplatin had an additive antiproliferative effect in SKNMC cells (60% reduction in cell number). A similar effect was observed in human MCF-7 breast cancer cells., Conclusion: STI-571 improves the outcome of cisplatin or irradiation treatment in vitro. AKT pathway may play a role in the additive effect of STI-571 and irradiation.

Objective: To determine the safety and outcome following standard-dose ibritumomab tiuxetan followed by BEAM high-dose chemotherapy and autologous stem cell transplantation (ASCT) in patients with chemo-refractory aggressive non-Hodgkin's lymphoma., Patients and Methods: The study included 23 patients, median age 55 years (range, 35-66) with chemo-refractory lymphoma, either primary refractory (n = 11) or in refractory relapse (n = 12). Rituximab 250 mg/m(2) followed by ibritumomab tiuxetan 0.4 mCi/kg were given on day -14 and high-dose BEAM chemotherapy started on day -6., Results: All patients engrafted. Twenty-one patients are evaluable for response; 11 achieved CR, 9 achieved PR, 5 of whom converted to CR with additional radiation therapy (overall CR rate 76%). With a median follow-up of 17 months (range, 4-27) 16 patients are alive and 12 are progression-free. The estimated 2-year overall and progression-free survival are 67% (95% CI, 46-87%) and 52% (95% CI, 31-72%), respectively. The day-100 rate of treatment-related mortality was 9% (95% CI, 2-33%) and the 2-year cumulative incidence of relapse was 31% (95% CI, 17-57%). Extensive prior therapy (>3 lines), high LDH and IPI score at ASCT, bulky disease, and progression during last chemotherapy were risk factors for reduced survival., Conclusion: Ibritumomab tiuxetan-BEAM and ASCT is relatively safe and may improve outcome in patients with refractory lymphoma. Although excess nonrelapse mortality can not be ruled out, relapse rate was relatively low, resulting in improved outcome. Standard-risk patients with chemo-sensitive disease may also benefit from ibritumomab tiuxetan-BEAM and ASCT. This hypothesis merits further study in larger-scale prospective randomized studies.

Background: We investigated physician rationale for and against performing routine erythrocyte sedimentation rate (ESR) tests during hospital admissions., Methods: A comparative, descriptive, prospective study among 82 physicians in 15 departments of internal medicine from two University Medical Centers - A and B - in Israel was conducted between July and August 2004. Reasons for physicians' use of ESR were examined using a confidential questionnaire. A panel of four experts reviewed the need to perform an ESR test in 100 patients' files from center B. The main outcome measures were the use of ESR in routine hospital admissions and reasons for use., Results: Forty-four vs. zero physicians from medical centers B and A, respectively, routinely perform ESR tests for all admitted patients (p<0.001). According to the experts, in only 10-30% of the 67 new patients could ESR tests have been of some value. Reasons for performing ESR routinely were as follows: to identify severe and "hidden" diseases (21/44, 47.7%); because it is crucial for all patients, both new and returning (10/44, 22.7%); because it is a guideline from department head (6/44, 13.6%); it is recommended in the literature (5/44, 11.4%); don't know why (2/44, 4.5%); defensive medicine (1/44, 2.3%); and other (6/44, 13.6%)., Conclusion: Routine use of ESR tests on admission can be explained by old habits and by an unconscious concern about liability, i.e., unconscious defensive medicine.

Potential profiles across molecular layers are constructed by means of noncontact electrically stimulated photoelectron spectroscopy, probing for the first time the molecule-substrate interface potential and resolving local screening effects across inner phenyl groups.

Routine post partum complete blood count examination (CBC) is customary in many medical centers. The rationale behind drawing a routine CBC is to estimate blood loss during delivery and to identify patients who will need blood transfusions. The present study was aimed to determine the necessity of routine post-partum CBC following vaginal delivery. A retrospective cohort study was performed including all patients who received blood transfusions following vaginal delivery between January 2003 and November 2004. Data were collected from birth files. The indications for administration of blood transfusions were noted. Of 20,694 vaginal deliveries, 0.7% (n = 138) received blood transfusions. All patients had at least one obstetric risk factor of postpartum hemorrhage or symptomatic anemia. None received the blood transfusion based upon postpartum CBC hemoglobin level alone. Routine postpartum CBC is not warranted for the purpose of identifying the patient in need of blood transfusions. Postpartum CBC should be performed when indicated according to risk factors for excessive blood loss or patients' complaints.

Objective: The objective was to investigate obstetric risk factors, complications, and outcomes of pregnancies complicated by moderate to severe thrombocytopenia., Materials and Methods: A retrospective case-control study comparing 199 pregnant women with moderate to severe thrombocytopenia (platelet count below 100x10(9)/l) with 201 pregnant women without thrombocytopenia, who delivered between January 2003 to April 2004. Stratified analysis, using the Mantel-Haenszel procedure was performed in order to control for confounders., Results: The main causes of thrombocytopenia were gestational thrombocytopenia (GT) (59.3%), immune thrombocytopenic purpura (ITP) (11.05%), preeclampsia (10.05%), and HELLP (Hemolysis, elevated liver enzymes and low platelet count) syndrome (12.06%). Women with thrombocytopenia were significantly older (30.7+/-5.9 versus 28.7+/-5.7; p=0.001) compared with patients without thrombocytopenia, and had higher rates of labor induction (OR=4.0, 95% CI=2.2-7.6, p<0.001) and preterm deliveries (OR=3.5, 95% CI=1.9-6.5, p<0.001). Even after controlling for labor induction, using the Mantel-Haenszel technique, thrombocytopenia was significantly associated with preterm delivery (weighted OR=3.14, 95% CI=1.7-6.0, p<0.001). Higher rates of placental abruption were found in pregnant women with thrombocytopenia (OR=6.2, 95% CI=1.7-33.2, p=0.001). In a comparison of perinatal outcomes, higher rates of Apgar scores <7 at 5 min were noted in infants of mothers with thrombocytopenia (OR=6.3, 95% CI=1.8-33.8, p=0.001), intrauterine growth restriction (IUGR; OR=4.6, 95% CI=1.5-19.1, p=0.003), and stillbirth (65/1000 versus 0 p<0.001). These adverse perinatal outcomes were found in rare causes of thrombocytopenia such as disseminated intravascular coagulation (DIC), familial thrombotic thrombocytopenic purpura (TTP), anti-phospholipid antibodies (APLA) syndrome, and myeloproliferative disease, and not among patients with GT., Conclusions: Moderate to severe maternal thrombocytopenia points to a higher degree of severity of the primary disease, which increases perinatal complications. However, the adverse outcome is specifically attributed to preeclampsia, HELLP syndrome, and rare causes, while the perinatal outcome of GT and ITP is basically favorable. Special attention should be given to patients with thrombocytopenia due to preeclampsia, HELLP syndrome, and rarer causes during pregnancy.

Background: Endobronchial stents are used to treat symptomatic patients with benign or malignant airway obstructions., Objectives: To evaluate the safety and outcome of airway stent insertion for the treatment of malignant tracheobronchial narrowing., Methods: The files of all patients with malignant disease who underwent airway stent insertion in our outpatient clinic from June 1995 to August 2004 were reviewed for background data, type of disease, symptoms, treatment, complications and outcome., Results: Airway stents were used in 34 patients, including 2 who required 2 stents at different locations, and one who required 2 adjacent stents (total, 37 stents). Ages ranged from 36 to 85 years (median 68). Primary lung cancer was noted in 35% of the patients and metastatic disease in 65%. Presenting signs and symptoms included dyspnea (82%), cough (11.7%), hemoptysis (9%), pneumonia (5.9%), and atelectasis (3%). The lesions were located in the left mainstem bronchus (31%), trachea (26%), right mainstem bronchus (26%), subglottis (14.3%), and bronchus intermedius (2.9%). Conscious sedation alone was utilized in 73% of the patients, allowing for early discharge. Eighteen patients (50%) received brachytherapy to the area of obstruction. Complications included stent migration (one patient) and severe or minimal bleeding (one patient each). Ninety-four percent of the patients reported significant relief of their dyspnea. Three of the four patients who had been mechanically ventilated before the procedure were weaned after stent insertion. Median survival from the time of stent placement was 6 months (range 0.25-105 months)., Conclusion: Stent placement can be safely performed in an outpatient setting with conscious sedation. It significantly relieves the patient's symptoms and may prolong survival.

Background: We compared the efficacy and toxicity of oral capecitabine and continuous infusion of 5-fluorouracil (5-FU) in the preoperative chemoradiation treatment of patients with rectal cancer., Patients and Methods: The files of 89 patients with rectal cancer, 43 treated preoperatively with oral capecitabine and 46 with intravenous 5-FU, were reviewed, and the outcome of the groups was compared., Results: There was no statistically significant difference in the complete pathological response rate between the capecitabine and the 5-FU groups (30% vs. 17%, P = 0.15). The downstaging rate was higher in the capecitabine group (77% vs. 50%, P = 0.009). Toxicity was mild in both groups. The rate of Grade 3 gastrointestinal toxicity was similar in the two groups (diarrhea 2% vs. 4%, proctitis 5% vs. 7%), except for one patient in the 5-FU group (2%) who developed a rectovaginal fistula. In the capecitabine group, one patient (2%) had Grade 3 hand-foot syndrome, and another had an acute myocardial infarction. In the 5-FU group, two patients (4%) had Grade 3 hematological toxicity, and three (6%) had complications from Port-a-Cath insertion., Conclusion: Preoperative chemoradiation with oral capecitabine appears to be safe and well tolerated, and at least as good as continuous 5-FU., (Copyright 2006 Wiley-Liss, Inc.)

Objective: The purpose of this study was to examine whether women with inherited thrombophilia have an increased risk of developing pregnancy complications., Methods: All singleton pregnancies with known inherited thrombophilia were compared to those without inherited thrombophilia for deliveries during the years 2000-2002 in a tertiary medical center. Data regarding inherited thrombophilia (International Classification of Disease 9th revision, Clinical Modification code 286.3) were available from the perinatal database in our center. Women lacking prenatal care were excluded from the analysis. Stratified analysis, using a multiple logistic regression model, was performed to control for confounders., Results: Out of 32,763 singleton deliveries that occurred during the study period, 0.2% (n=57) of the women were diagnosed with inherited thrombophilia. Using a multivariate analysis, with backward elimination, the following conditions were significantly associated with inherited thrombophilia: previous fetal losses [odds ratio (OR)=5.5; 95% confidence interval (CI) 2.9-10.3; P<0.001], recurrent abortions (OR=9.5; 95% CI 5.5-16.3; P<0.001), fertility treatments (OR=3.7; 95% CI 1.3-10.6; P=0.014), and intrauterine growth restriction (OR=7.2; 95% CI 3.4-15; P<0.001). Perinatal mortality was significantly higher in women with inherited thrombophilia than in those without known thrombophilia 5.3% (3/57) versus 0.6% (477/32,763) P=0.017. However, inherited thrombophilia was not found to be an independent risk factor for perinatal mortality (OR=3.05; 95% CI 0.90-10.3; P<0.073) in a multivariate analysis with perinatal mortality as the outcome variable, controlling for recurrent abortions, IUGR, and gestational age., Conclusion: Inherited thrombophilia, associated with previous fetal losses, recurrent abortions, fertility treatments, and intrauterine growth restriction, was not an independent risk factor for perinatal mortality.

Purpose: The purpose of this study was to describe our department's experience with the fused imaging-guided radiotherapy (FIGURA) system for planning radiation treatment of high-risk neuroblastoma., Patients and Methods: Between 1999 and 2002, 11 patients received radiation therapy as consolidation after chemotherapy in 9 and for palliation in 2. Diagnostic metaiodobenzylguanidine (MIBG) imaging was used, which is specific for neuroblastoma, to identify the residual tumor, followed by computed tomography scanning in the radiation treatment position. The FIGURA software fused the images obtained by the 2 modalities and transferred the result to a 3-dimensional radiation treatment planning system. Radiation was delivered at a total dose of 25.2 Gy according to the FIGURA., Results: Five patients achieved complete remission and 2 partial remission; 3 were stabilized. One child with a highly rapid progressive course died of the disease., Conclusion: FIGURA is a new, feasible technique for defining target volumes. By using standard hospital equipment, it is possible to treat residual disease identified by sensitive metaiodobenzylguanidine imaging and localized with the anatomic computed tomography scan. Treating a more accurate target volume spares normal tissue and organs and minimizes side effects.

In young women treated for intermediate-high-grade non-Hodgkin's lymphoma with CHOP (cyclophosphamide, adriamycin, oncovine and prednisone), there is insufficient data concerning gonadotoxicity or the need for fertility-preserving measures. The aim of the present study was to evaluate the fertility status in the first complete remission of women who were treated for aggressive non-Hodgkin's lymphoma. A cohort of 36 women with aggressive non-Hodgkin's lymphoma in first remission, who were treated in five university-affiliated hospitals in Israel, was evaluated. All women were aged younger than 40 years at diagnosis and received frontline protocols, including cyclophosphamide and adriamycin, mostly CHOP. Menstrual cycle characteristics, as well as pregnancies before the diagnosis, during treatment and in first complete remission, were evaluated. The patients' mean age at the diagnosis was 28 +/- 7 years (range 17 - 40 years). All patients were treated with chemotherapy, although 10 patients received additional radiotherapy. Follow-up time at first complete remission was 84 +/- 48 months. Before diagnosis, all patients had menstrual cycles, which were regular in 31 (86%). Three patients received gonadtropin-releasing hormone analogs, whereas nine received contraceptive pills together with cytotoxic treatment. During treatment, 18 patients (50%) had amenorrhea, six (17%) had irregular menstrual cycles, and 12 (33%) continued their regular cycles. All but two women resumed menses in the first complete remission, and these were regular in 22 (61%) patients. In 63% of patients, the menstrual cycle recovered within 3 months of the discontinuation of chemotherapy. Eighteen patients (50%) became pregnant during the first complete remission. There was no significant difference between those patients who received fertility-preserving measures versus the remainder concerning regular menstrual cycles recovery or pregnancies. The two patients who developed amenorrhea were 40 years old at the time of diagnosis. In conclusion, the rate of gonadal dysfunction is very low among young, CHOP treated, non-Hodgkin's lymphoma female patients. Fertility-preserving techniques are not needed for women aged younger than 40 years and should probably be reserved for those who are at high risk for gonadal toxicity.

Allogeneic stem-cell transplantation (SCT) with both myeloablative and reduced-intensity conditioning (RIC) is an effective therapy in AML/MDS. However, the relative merits of each may differ in different settings. To define the role of dose intensity, we analyzed SCT outcomes of 112 consecutive patients with AML/MDS. A total of 45 patients met eligibility criteria for standard myeloablative conditioning and were given intravenous-busulfan (12.8 mg/kg) and cyclophosphamide (ivBuCy). A total of 67 noneligible patients were given RIC with fludarabine and intravenous-busulfan (6.4 mg/kg, FB2, n=41) or a modified myeloablative regimen with fludarabine and myeloablative doses of intravenous-busulfan (12.8 mg/kg, FB4, n=26). The overall survival (OS) at 2 years was 50, 49 and 47% after ivBuCy, FB4 and FB2, respectively (P=NS). Nonrelapse mortality was higher after ivBuCy, 22 vs 8% (P=0.05), but relapse rates were lower. Active disease at SCT was the most significant predictor of reduced survival in multivariable analysis (HR 4.5, P=0.0001). Myeloablative and RIC regimens had similar outcomes when leukemia was in remission at SCT; however, patients with active disease could only be salvaged by myeloablative conditioning. Among the latter, OS was 45% after ivBuCy but no FB2 recipient survived (P=0.02). Patients with active disease, ineligible for standard myeloablation, could tolerate modified myeloablation well; however, long-term outcome cannot be determined yet.

Hydrogen bonds play an important role in an overwhelming variety of fields from biology to surface and supramolecular chemistry. The term "hydrogen bond" refers to a wide range of interactions with various covalent and polar contributions. In particular, hydrogen bonds have an important role in the folding and packing of peptides and nucleic acids. Recent studies also point to the importance of hydrogen bonding in the context of second-shell interactions, in metal binding and selectivity in metalloproteins, and in controlling the dynamics of membrane proteins. In this study, we demonstrate and quantify the modulation of fragmental charge transfer from hydrogen-bonded ligands to a metal center, by employing our recently introduced molecular potentiometer. The molecular details that affect this type of fragmental charge transfer are presented and a path for transferring chemical information is demonstrated. We found that H-bond interactions in the extended positions of axial ligands provide an effective means of modulating the amount of fragmental charge transfer to a metal center, thereby dramatically influencing the electronic properties of the ligand, the binding affinity, and the binding of additional ligands. The magnitude of fragmental charge-transfer modulation induced by a single ligand-solvent H-bond interaction is comparable to those induced by covalent substitution, although H-bond enthalpy is only on the order of several kilojoules per mole. Importantly, we find a significant change in the ligand electronic properties, even for weak C-H...O=C H-bond formation, where the bond enthalpy is substantially lower than for conventional H-bond interactions. The excess fragmental charge transferred to the metal center, deduced from the spectroscopic measurements, correlates well with the computationally determined values. Our findings underscore the importance of second-shell interactions in the active sites of enzymes, beyond the structural and electrostatic importance that is widely recognized today.

The aim of the presented study was to evaluate the long-term outcome of breast-conserving surgery and radiation for the treatment of ductal carcinoma in situ (DCIS) and the role of the radiation boost to the tumor bed. The files of 75 women with DCIS treated by breast-conserving surgery followed by definitive radiation from 1988 to 1997 were reviewed for demographic data, prognostic variables, radiation dose, radiation boost, recurrence, and outcome. Total radiation dose was 5000 cGy delivered in 25 fractions. Twenty patients (26.7%) received an additional boost to the tumor bed of 1000 cGy in 5 fractions. Median follow-up time was 81.5 months (range, 22-145). Pearson correlation coefficient and its significance was calculated between the variables. Log rank test was used to analyze differences in local recurrence rates between patients who did or did not receive a boost, and a Cox regression model was fitted to the data to predict recurrence. Ten patients (13%) had local recurrence; one patient showed lymphatic spread. Histopathologic examination revealed DCIS in 6 cases (60%) and invasive duct carcinoma in 4 (40%)(one minimally invasive). The recurrence group included 3 of the 20 patients who received a radiation boost (15%) and 7 of the 55 who did not (12.7%) (p=0.7). Correlation analysis of patient characteristics, prognostic factors, and treatment was significant only between mastitis as the presenting symptom (n=4) and longer time to recurrence (p=0.02). The recurrence rate in the present study was similar to other series of conservative treatment for DCIS of the breast. No additional value was found for the radiation boost. Larger controlled randomized studies are needed to confirm these findings.

Imatinib mesylate (IM) is a tyrosine kinase inhibitor, which inhibits phosphorylation of downstream proteins involved in BCR-ABL signal transduction. It has proved beneficial in treating patients with chronic myeloid leukaemia (CML). In addition, IM demonstrates activity against malignant cells expressing c-kit and platelet-derived growth factor receptor (PDGF-R). The activity of IM in the blastic crisis of CML and against various myeloma cell lines suggests that this drug may also target other cellular components. In the light of the important role of telomerase in malignant transformation, we evaluated the effect of IM on telomerase activity (TA) and regulation in various malignant cell lines. Imatinib mesylate caused a dose-dependent inhibition of TA (up to 90% at a concentration of 15 microM IM) in c-kit-expressing SK-N-MC (Ewing sarcoma), SK-MEL-28 (melanoma), RPMI 8226 (myeloma), MCF-7 (breast cancer) and HSC 536/N (Fanconi anaemia) cells as well as in ba/F3 (murine pro-B cells), which do not express c-kit, BCR-ABL or PDGF-R. Imatinib mesylate did not affect the activity of other DNA polymerases. Inhibition of TA was associated with 50% inhibition of proliferation. The inhibition of proliferation was associated with a decrease in the S-phase of the cell cycle and an accumulation of cells in the G2/M phase. No apoptosis was observed. Inhibition of TA was caused mainly by post-translational modifications: dephosphorylation of AKT and, to a smaller extent, by early downregulation of hTERT (the catalytic subunit of the enzyme) transcription. Other steps of telomerase regulation were not affected by IM. This study demonstrates an additional cellular target of IM, not necessarily mediated via known tyrosine kinases, that causes inhibition of TA and cell proliferation.

A general approach is demonstrated for the formation of monolayers comprised of free-base and metalated Bacteriochlorophyll-based derivatives providing a new vehicle for studying photosynthetic motifs and chromophore thin-film interactions. Accessibility to covalent and self-assembled systems on conducting, semiconducting, and insulating substrates is realized utilizing identical molecular building blocks. The monolayers retain the optical features typical for the new systems in solution. Molecular organization of chromophore interaction motifs can be sequentially designed using preassembled building blocks in solution and expressed in the thin film optical properties. For instance, intramolecular pi-pi stacking is conserved for the dimeric Ni-based chromophores as deduced from the spectroscopic measurements of the monolayers and in solution.

Chemotherapy and radiotherapy have been the principal modalities of treatment for diffuse large B-cell non-Hodgkin's lymphoma (B-NHL) for over 30 years. Various treatment regimens have been designed over the years to try to increase response and cure rates. The role of surgery has been generally restricted to defined and limited situations including diagnostic tissue biopsies and treating abdominal emergencies such as organ rupture or perforation. We present two cases of refractory B-NHL, where surgery was used as a part of stepwise and multi-modal treatment with curative intent. In both cases, the treatment approach included standard dose chemotherapy, eradication of residual mass by surgery, high dose chemotherapy (HDC) with stem cell support and posttransplantant immunotherapy. Currently, 2 years after completing the therapy, both patients are well with no evidence of active disease. Based on our experience with 2 patients we believe that in specific cases of residual chemo-resistant lymphomatous mass, surgery should be considered as a part of a multimodal approach., (Copyright 2004 Taylor and Francis Ltd)

In the present study, we have conducted a meta-analysis comparing autologous bone marrow transplantation (ABMT) and intensive chemotherapy in adult acute myeloid leukemia (AML) patients in first remission. Combined results of the six appropriate randomised controlled studies indicate that ABMT had no advantage over chemotherapy or no further treatment concerning death rate (overall rate ratio (RR)-0.95, 95% CI, 0.81-1.11), while was superior to chemotherapy concerning event rate (overall RR--0.82, 95% CI, 0.71-0.94). In conclusion, ABMT did not improve survival but it improved event-free survival (EFS) when compared with chemotherapy or no further treatment in patients with AML in first complete remission.

The remarkable advances accomplished in the past two decades in theoretical and computational capabilities have made the in silico study of complex chemical systems feasible. However, this progress is in strong contrast to the lag in experimental capabilities relating to the measurement of fundamental chemical quantities within convoluted environments such as solvents or protein milieu. As a result, many works rely extensively on predictions provided by ab initio methodologies without having independent experimental support. Such a proliferation of theory and computational approaches without being substantiated by appropriate experimental data is undesirable. The feasibility of using nickel-bacteriochlorophyll as a molecular potentiometer was recently demonstrated for the systematic evaluation of fragmental charge density transfer for metal complexes in solution, thus providing an experimental assay with high accuracy and sensitivity (better than +/-0.005 e(-); Yerushalmi, R.; Baldridge, K. K.; Scherz, A. J. Am. Chem. Soc. 2003, 125, 12706-12707). Here the experimentally determined fragmental charge density transfer values measured by the molecular potentiometer for metal complexes in solvent are used to provide, for the first time, an independent and critical experimental evaluation of theoretical approaches commonly used in determining atomic charges and fragmental charge density transfer among interacting molecular systems. Importantly, these findings indicate that the natural population analysis (NPA) charge analysis is highly robust and well-suited for determining charge transfer processes involving donor-acceptor coordination interactions. The majority of computational charge schemes fail to provide an accurate chemical picture for the whole range of systems considered here. In cases where the role of electronic correlation varies significantly among chemically related structures, as with mono- and biligated complexes, the widely used electrostatic potential fit-based methods for evaluating atomic charges may prove to be problematic for predictive studies. In such cases, alternative methods that do not rely on the net dipole moment or other higher multipoles of the system for determining charges should be employed.

Renal failure is known to occur in lymphoproliferative disorders because of ureteral obstruction or parenchymal infiltration by disease. Rituximab is a genetically engineered chimeric murine/human monoclonal antibody directed against the CD20 antigen found on the surface of normal and malignant B-lymphocytes. The pharmacokinetics and metabolism of rituximab is not well established. The extent of renal clearance is not fully known, with little experience reported on the use of rituximab in patients with renal failure. We present a case where rituximab was administered to a patient with acute renal failure due to bilateral kidney infiltration by non-Hodgkin's lymphoma (NHL). The patients renal function improved on therapy, with no need for hemodialysis and there were no significant toxicities. Rituximab may be used as a treatment option for NHL patients with impaired renal function.

We demonstrate the design and formation of thin films having divergent physicochemical properties by using two porphyrin building blocks with high chemical and optical resemblance. A predetermined variation in the molecular design is efficiently transferred and enhanced when constituting a two-dimensional film via control of molecular orientation. Variations of the peripheral substituents on the porphyrin ring resulted in control of the molecular orientation at the surface.

The prediction and measurement of charge distribution among interacting chemical entities in complex environments is a major challenge for modern chemistry. It encompasses information concerning fundamental quantities such as the electronic chemical potential and hardness of molecular fragments as well as their interactions with the surroundings. Although a wealth of theoretical work has been accumulated from the days of Pauling to the present, a specific molecular model system that allows quantitative and direct measurement of these properties has not yet been reported. Because atomic charges are not quantum mechanical observables, they cannot be derived from first principles, but rather they rely on the availability of high-precision experimental data and the interpretation of related experimental observables. Here, we demonstrate, for the first time, that a fragmental charge flow between a chelated metal center and reversibly bound molecules can be accurately monitored experimentally.

Background: Among the diseases imported by the Ethiopian immigrants to Israel are many parasite infections. Hookworm infections, caused by the nematodes Necator americanus and Ancylostoma duodenale, involve the gastrointestinal tract, causing iron-deficiency anemia., Objectives: To evaluate the rate of iron-deficiency anemia related to hookworm infections among immigrants from an endemic area., Methods: We retrospectively studied the medical records of all Ethiopians over the age of 18, who immigrated to Israel in the early 90's, in two primary care clinics of Clalit Health Services in Ofakim., Results: Sixty patients (64%) had evidence of A. duodenale infection. The mean hemoglobin level was 11.92.3 g/dl in the Ancylostoma group and 13.81.6 g/dl in the control group (p = 0.0001). Analyzing the data according to the patient's sex revealed significant differences in the hemoglobin levels between the Ancylostoma group and the control group. Patients infected with A. duodenale had significantly lower mean corpuscular volume (MCV) and serum iron, and were likely to have eosinophilia and hypoalbuminemia., Conclusion: Among the Ethiopian immigrant population, Ancylostoma duodenale infection is a common cause of iron deficiency anemia. In young patients it should be ruled out before invasive and expensive investigations are performed.

Hypersensitivity reactions to intravenous cisplatin are rare. The appearance of hypersensitivity reactions in 4 of 25 consecutive patients treated with concomitant pelvic radiation and weekly intravenous cisplatin for gynecologic malignancies is reported. The reactions appeared within hours of cisplatin delivery and included primarily fever, rash, and pruritus. Infection was ruled out by blood cultures and other laboratory studies. Affected patients were treated prophylactically with an antihistamine before subsequent courses of cisplatin, with excellent results. The high rate of hypersensitivity reactions in our series may be attributable to tumor necrosis and cytokine release caused by the pelvic irradiation. Clinicians should be aware of this potential side effect so that early premedication regimens can be instituted to prevent unnecessary toxicity.

Modification of the metal's electronic environment by ligand association and dissociation in metalloenzymes is considered cardinal to their catalytic activity. We have recently presented a novel system that utilizes the bacteriochlorophyll (BChl) macrocycle as a ligand and reporter. This system allows for charge mobilization in the equatorial plane and experimental estimate of changes in the electronic charge density around the metal with no modification of the metal's chemical environment. The unique spectroscopy, electrochemistry and coordination chemistry of [Ni]-bacteriochlorophyll ([Ni]-BChl) enable us to follow directly fine details and steps involved in the function of the metal redox center. This approach is utilized here whereby electro-chemical reduction of [Ni]-BChl to the monoanion [Ni]-BChl(-) results in reversible dissociation of biologically relevant axial ligands. Similar ligand dissociation was previously detected upon photoexcitation of [Ni]-BChl (Musewald, C.; Hartwich, G.; Lossau, H.; Gilch, P.; Pollinger-Dammer, F.; Scheer, H.; Michel-Beyerle, M. E. J. Phys. Chem. B 1999, 103, 7055-7060 and Noy, D.; Yerushalmi, R.; Brumfeld, V.; Ashur, I.; Baldridge, K. K.; Scheer, H.; Scherz, A. J. Am. Chem. Soc. 2000, 122, 3937-3944). The electrochemical measurements and quantum mechanical (QM) calculations performed here for the neutral, singly reduced, monoligated, and singly reduced, monoligated [Ni]-BChl suggest the following: (a) Electroreduction, although resulting in a pi anion [Ni]-BChl(-) radical, causes electron density migration to the [Ni]-BChl core. (b) Reduction of nonligated [Ni]-BChl does not change the macrocycle conformation, whereas axial ligation results in a dramatic expansion of the metal core and a flattening of the highly ruffled macrocycle conformation. (c) In both the monoanion and singly excited [Ni]-BChl ([Ni]-BChl*), the frontier singly occupied molecular orbital (SOMO) has a small but nonnegligible metal character. Finally, (d) computationally, we found that a reduction of [Ni]-BChl*imidazole results in a weaker metal-axial ligand bond. Yet, it remains weakly bound in the gas phase. The experimentally observed ligand dissociation is accounted for computationally when solvation is considered. On the basis of the experimental observations and QM calculations, we propose a mechanism whereby alterations in the equatorial pi system and modulation of sigma bonding between the axial ligands and the metal core are mutually correlated. Such a mechanism highlights the dynamic role of axial ligands in regulating the activity of metal centers such as factor F430 (F430), a nickel-based coenzyme that is essential in methanogenic archea.

Our previous studies have demonstrated that basic fibroblast growth factor (bFGF) inhibits the growth of MCF-7 human breast cancer cells via binding to high affinity cell surface receptors. The downstream signaling of bFGF was reported to involve the ras pathway. The aim of the present study was to examine the bFGF-induced growth inhibition in the presence of lovastatin, a farnesyl transferase inhibitor, which impaired ras signaling by preventing its association with the plasma membrane. We found that the combined cytotoxicity induced by lovastatin and bFGF was greater than the cytotoxicity induced by each agent alone. Similarly, the protein level of P21/WAF1/cip1 was greater after exposure to both agents together, than separately. bFGF did not interfere with the lovastatin-induced inhibition of P21/RAS membrane association, while lovastatin did not prevent MAPK activation by bFGF. Based on these findings we suggest that the growth inhibitory effect of bFGF on breast cancer cells is largely independent of the ras signaling pathway. Understanding these pathways may enable active intervention to alter the therapeutic ratio favorably in the treatment of breast cancer.

Unlabelled: A 64-year-old woman was diagnosed as suffering from ovarian cancer. At that time, in 1984, she was treated with chemotherapy and complete remission was achieved. The disease recurred 2.5 years later and chemotherapy was delivered again. The patient remained disease free for 9 years. At that point a routine blood examination revealed a high serum level of the marker CA-125. A second recurrence of ovarian cancer was assumed. Nonetheless, work up revealed that the rise in CA-125 was related to the presence of a non-Hodgkins lymphoma (NHL)., Conclusions: This case together with our review of the literature highlights the emerging roll of the CA-125 marker in the diagnosis and follow-up of non-Hodgkins lymphoma. Our case also illustrates that physicians should be aware of the fact that markers may be misleading.

Purpose: To ascertain the predictive value of Her-2/neu overexpression and p53 mutations, assessed by immunohistochemistry, in high-risk primary breast cancer (HRPBC) treated with high-dose chemotherapy (HDCT)., Patients and Methods: We obtained paraffin-embedded tumor blocks from 146 HRPBC patients previously enrolled at our program onto clinical trials of HDCT for four to nine involved axillary lymph nodes, > or = 10 involved axillary nodes, or inflammatory carcinoma. All patients received the same HDCT regimen, with cyclophosphamide, cisplatin, and carmustine (STAMP-I), followed by autologous stem-cell transplantation. Median follow-up was 42 months (range, 5 to 90 months). The same pathologist, blinded to clinical outcome, reviewed all immunostained slides., Results: Positive results for Her-2/neu and p53 were found in 44.5% and 34% of the patients, respectively. Positivity for Her-2/neu was significantly associated with increased risk of relapse and death. No correlation was found between p53 mutations and relapse-free survival (RFS) or overall survival (OS). Multivariate analyses included Her-2/neu overexpression and the following variables previously identified as independent predictors of outcome in this population: tumor size, nodal ratio (number of involved nodes/number of dissected nodes), and hormone receptor status. All four variables had independent value., Conclusion: Her-2/neu overexpression is an independent negative predictor of RFS and OS in HRPBC treated with HDCT. Its inclusion in our previously described predictive model increases the predictive capacity of this model for the low-risk subgroup. In contrast, p53 mutations lack predictive value in this setting.

Objective: To improve the accuracy of cytologic diagnosis in breast lesion aspirates that are cytologically suggestive of fibroadenoma (FA), exhibiting proliferating epithelial elements and bare nuclei but devoid of the typical stroma., Study Design: A retrospective study was conducted. All available cases (89) that were aspirated and reported as suggestive of FA between 1981 and 1991 and were later biopsied were studied, and various morphologic criteria were analyzed in each smear. A control group consisted of 43 cases that were cytologically diagnosed as FA and confirmed histologically., Results: Two criteria contributed to the cytologically suggestive diagnosis of FA. The presence of numerous "multilayered" fragments of proliferating glandular epithelium improved the positive predictive value (PPV) for FA on the suggestive smear from 67.4% to 88.3%, and the presence of numerous bare nuclei in the background improved it to 88.9%. The combined presence of both criteria improved the PPV even further, to 91.7%., Conclusion: When an aspirate from a breast lesion is cytologically suggestive of FA despite the absence of the typical stroma, a PPV of 91.7% can be achieved, provided that the epithelial elements include many "multilayered" fragments and that the background consists of numerous bare nuclei.

Werner's syndrome is a rare clinical entity and approximately 150 cases have been reported in the medical literature. Werner's syndrome, inherited by autosomal recessive transmission, is characterized primarily by a short stature, premature greying and balding, trophic ulceration of the legs, diabetes mellitus and hypogonadism. These features combine to present a picture of adult progeria. In this brief report we describe a 51-year-old Bedouin male with Werner's syndrome, diagnosed as erythroleukemia (AML-6), and presenting as acute pancytopenia. The patient died two months after diagnosis. This is a rare case of erythroleukemia in a patient with Werner's syndrome. We survey current knowledge of the cytogenetic pathogenesis of Werner's syndrome and erythroleukemia, and attempt to explain the possible link between these two rare syndromes.