ORCID Profile
0000-0002-6419-7813
Current Organisations
St Vincent's Hospital Melbourne
,
University of Melbourne
Does something not look right? The information on this page has been harvested from data sources that may not be up to date. We continue to work with information providers to improve coverage and quality. To report an issue, use the Feedback Form.
Publisher: Elsevier BV
Date: 1984
DOI: 10.3109/00313028409059089
Abstract: The influence of material released by activated human platelets on the phagocytic activity of human neutrophils and monocytes has been investigated under conditions where there was a low background level of exposure of the leukocytes to platelet release products (PRPr). Incubation with PRPr prepared from 400 X 10(9)/l platelets resulted in an approximate 3-fold increase in the proportion of leukocytes which ingested particles. Stimulation was produced by dilutions of PRPr down to 1:4 to indicate that phagocytic activity was affected by material released by concentrations of platelets within the physiological range. This response appeared to reflect stimulation of the overall phagocytic capability of the leukocytes as equivalent ingestion was observed with particles which possessed or lacked the capacity to bind complement to their surface. Enhancement of phagocytic activity was evidently secondary to induction of a change in leukocyte behaviour which was sustained in the absence of continued exposure to preparations of PRPr. These observations extend the range of human biological processes known to be responsive to PRPr, and have implications for the assessment of leukocyte phagocytic activity in vitro as this particular property could be modified by contact with PRPr during the isolation of leukocytes from peripheral blood.
Publisher: American Physical Society (APS)
Date: 05-10-2020
Publisher: Elsevier BV
Date: 09-2020
Publisher: Wiley
Date: 03-1969
Publisher: Therapeutic Guidelines Limited
Date: 02-1999
Publisher: Wiley
Date: 06-2003
DOI: 10.1046/J.1365-2141.2003.04385.X
Abstract: The characteristics of severe neutropenia with a delayed onset following administration of rituximab have been evaluated in 53 consecutively treated patients. All but one patient received rituximab for the treatment of non-Hodgkin's lymphoma. Eight episodes of grade 4 neutropenia were detected between 1 and 5 months after rituximab, when administered alone on five occasions, and on three occasions in combination with chemotherapy, where neutrophil counts had recovered prior to the development of neutropenia. In three episodes, the patients presented with sepsis. Development of neutropenia did not correlate with either the presence of detectable disease or the administration of further treatment. Neutropenia was associated with selective depletion of neutrophil precursors in all but one episode, where it was associated with generalized bone marrow hypoplasia. All episodes developed after a period of either normal or mildly depressed neutrophil counts following treatment with rituximab, and persisted for between several days and several months, before undergoing spontaneous recovery in four instances, and after administration of filgrastim in the remainder. Episodes of neutropenia were associated with disordered immune status manifested by lymphopenia and hypogammaglobulinaemia, raising the possibility that either disturbance of the balance of lymphocyte subsets or an immune dyscrasia induced by rituximab resulted in the development of this type of neutropenia.
Publisher: Wiley
Date: 10-1975
Abstract: Cells from regenerating mouse liver removed 2-25 days post 68% hepatic resection have been assayed for in vivo colony forming capacity in soft agar (CFU-C), proliferative capacity in liquid culture, and in vivo spleen colony forming capacity (CFU-S). These studies demonstrated low concentrations of CFU-C and CFU-S in normal and sham operated liver, with an appreciable increase of both in regenerating liver, reaching maximum values in tissue removed 5--7 days post hepatic resection. Colony formation in agar by regenerating liver cells occurred in the absence of exogenous colony stimulating factor. Separation of liver cells on the basis of adherent properties prior to culture indicated concentration of CFU-C in the non-adherent fraction, while cells producing colony stimulating factor were concentrated in the adherent fraction. Foci of actively iding cells of themacrophage and granulocyte series arose in liquid culture from preparations of sham operated and regenerating liver, although total cell formation was greater with regenerating liver. A small proportion of the colonies formed in agar from regenerating liver consisted of cords of epithelioid cells, which resembled hepatocytes and differed from the macrophages or granulocytes found in the majority of colonies, raising the possibility that regenerating hepatocytes form colonies in agar culture.
Publisher: Elsevier BV
Date: 1971
Publisher: Springer Science and Business Media LLC
Date: 12-2020
DOI: 10.1140/EPJC/S10052-020-08562-Y
Abstract: Measurements are presented of the single-diffractive dijet cross section and the diffractive cross section as a function of the proton fractional momentum loss $$\xi $$ ξ and the four-momentum transfer squared t . Both processes $${\text{ p }{}{}} {\text{ p }{}{}} \rightarrow {\text{ p }{}{}} {\text{ X }} $$ p p → p X and $${\text{ p }{}{}} {\text{ p }{}{}} \rightarrow {\text{ X }} {\text{ p }{}{}} $$ p p → X p , i.e. with the proton scattering to either side of the interaction point, are measured, where $${\text{ X }} $$ X includes at least two jets the results of the two processes are averaged. The analyses are based on data collected simultaneously with the CMS and TOTEM detectors at the LHC in proton–proton collisions at $$\sqrt{s} = 8\,\text {Te}\text {V} $$ s = 8 Te during a dedicated run with $$\beta ^{*} = 90\,\text {m} $$ β ∗ = 90 m at low instantaneous luminosity and correspond to an integrated luminosity of $$37.5{\,\text {nb}^{-1}} $$ 37.5 nb - 1 . The single-diffractive dijet cross section $$\sigma ^{{\text{ p }{}{}} {\text{ X }}}_{\mathrm {jj}}$$ σ jj p X , in the kinematic region $$\xi 0.1$$ ξ 0.1 , $$0.03 |t | 1\,\text {Ge}\text {V} ^2$$ 0.03 | t | 1 Ge 2 , with at least two jets with transverse momentum $$p_{\mathrm {T}} 40\,\text {Ge}\text {V} $$ p T 40 Ge , and pseudorapidity $$|\eta | 4.4$$ | η | 4.4 , is $$21.7 \pm 0.9\,\text {(stat)} \,^{+3.0}_{-3.3}\,\text {(syst)} \pm 0.9\,\text {(lumi)} \,\text {nb} $$ 21.7 ± 0.9 (stat) - 3.3 + 3.0 (syst) ± 0.9 (lumi) nb . The ratio of the single-diffractive to inclusive dijet yields, normalised per unit of $$\xi $$ ξ , is presented as a function of x , the longitudinal momentum fraction of the proton carried by the struck parton. The ratio in the kinematic region defined above, for x values in the range $$-2.9 \le \log _{10} x \le -1.6$$ - 2.9 ≤ log 10 x ≤ - 1.6 , is $$R = (\sigma ^{{\text{ p }{}{}} {\text{ X }}}_{\mathrm {jj}}/\Delta \xi )/\sigma _{\mathrm {jj}} = 0.025 \pm 0.001\,\text {(stat)} \pm 0.003\,\text {(syst)} $$ R = ( σ jj p X / Δ ξ ) / σ jj = 0.025 ± 0.001 (stat) ± 0.003 (syst) , where $$\sigma ^{{\text{ p }{}{}} {\text{ X }}}_{\mathrm {jj}}$$ σ jj p X and $$\sigma _{\mathrm {jj}}$$ σ jj are the single-diffractive and inclusive dijet cross sections, respectively. The results are compared with predictions from models of diffractive and nondiffractive interactions. Monte Carlo predictions based on the HERA diffractive parton distribution functions agree well with the data when corrected for the effect of soft rescattering between the spectator partons.
Publisher: Wiley
Date: 08-1990
DOI: 10.1111/J.1365-2141.1990.TB07785.X
Abstract: Alterations in neoplastic cell behaviour responsible for increased production of terminally-differentiated granulocytes during long-term culture of bone marrow in different categories of acute leukaemia and myelodysplasia have been investigated. An increase in neutrophils associated with transition to a morphological picture identical to normal control cultures occurred in 15 of 25 studies on acute leukaemia in contrast to one of six studies on myelodysplastic disorders. An abnormal neoplastic karyotype was employed as a marker for monitoring the course of the neoplastic cell population in 11 studies in which there was progression towards a normal pattern of differentiation. An increase in differentiation was shown by this means to represent increased maturation of cells of the neoplastic process in one study on a myelodysplastic disorder, demonstrating domination of proliferative activity in culture by all of the myelodysplastic disorders examined. Transition towards normal differentiation in nine studies on acute leukaemia, however, correlated with partial or complete replacement of the acute leukaemic cells by normal haemopoietic series in de novo acute leukaemia, and by Ph positive cells in blast crisis of CML. Conversion to morphologically and cytogenetically normal cell populations in five studies on de novo acute leukaemia occurred in four cases which failed to respond to remission-induction therapy, suggesting the selective toxic effect capable of purging acute leukaemic cells from bone marrow operated by a mechanism which lacked cross-resistance to currently-employed cytotoxic agents.
Publisher: American Society of Hematology
Date: 05-1980
Publisher: Wiley
Date: 09-1998
DOI: 10.1046/J.1365-2141.1998.00918.X
Abstract: Severe iron overload is a reported complication of certain erythroid disorders which are characterized by increased erythropoietic activity. Proposed mechanisms include enhancement of iron absorption secondary to increased erythroid activity and coexistent heterozygosity or homozygosity for haemochromatosis. We performed PCR-based analysis for the haemochromatosis-related HFE C282Y mutation in an extended family with inherited haemolytic anaemia in which several members exhibited iron overload. The results demonstrated iron overload was associated with homozygosity but not heterozygosity for this mutation. Such an association may also exist in other erythroid disorders in which iron overload has been reported.
Publisher: American Physical Society (APS)
Date: 09-11-2020
Publisher: American Society of Clinical Oncology (ASCO)
Date: 04-1994
DOI: 10.1200/JCO.1994.12.4.769
Abstract: To compare complete response rates, time to failure, survival, and toxicity for patients with intermediate-grade non-Hodgkin's lymphoma (NHL) treated with cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) versus those treated with a regimen consisting of methotrexate, doxorubicin, cyclophosphamide, vincristine, prednisolone, and bleomycin (MACOP-B), in a multicenter, randomized controlled trial performed by 22 centers of the Australian and New Zealand Lymphoma Group (ANZLG). Between October 1986 and June 1991, 304 patients were randomized, of whom 236 were eligible for analysis. Eligibility criteria included diffuse small cleaved-cell, diffuse mixed small- and large-cell, follicular large-cell, diffuse large-cell, and large-cell immunoblastic, stages I bulky or II to IV. There was no significant difference in complete response rates (51% for MACOP-B v 59% for CHOP), failure-free survival, or overall survival in the two treatment arms. The rate of death of MACOP-B patients relative to CHOP patients was estimated to be 0.91 (P = .64) when stratified by prognostic group. There were no significant differences between the two regimens in any of the prognostic subgroups. Toxicity was significantly more severe with MACOP-B, particularly cutaneous toxicity, stomatitis, and gastrointestinal ulceration. The average relative dose-intensity (RDI) of MACOP-B was 0.91 and of CHOP was 0.90, indicating good dose delivery in this multicenter group setting. CHOP chemotherapy produced results equivalent to those of MACOP-B in patients with intermediate-grade NHL and with significantly fewer toxic complications. Despite relatively poor results in some patient subgroups, CHOP remains the standard chemotherapy for this disease, against which all new regimens should be compared.
Publisher: American Physical Society (APS)
Date: 16-11-2020
Publisher: Elsevier BV
Date: 04-1969
Publisher: IOP Publishing
Date: 15-09-2020
Publisher: Japanese Society of Inflammation and Regeneration
Date: 1982
Publisher: American Physical Society (APS)
Date: 24-04-2020
Publisher: Elsevier BV
Date: 1997
DOI: 10.1080/00313029700169455
Abstract: Disseminated enteric human cytopathogenic orphan (echo) virus infection after allogeneic bone marrow transplantation has been reported once previously: a patient developed a fatal infection with the virus being isolated from brain, lung and heart. We report a second case of disseminated echovirus infection in which virus was isolated from the stomach and liver. On this occasion the infection was associated with the development of biopsy-proven acute graft-versus-host disease of the skin, stomach, colon and liver. The infection resolved without sequelae.
Publisher: BMJ
Date: 02-12-1978
Publisher: American Physical Society (APS)
Date: 05-08-2020
Publisher: Elsevier BV
Date: 1984
Publisher: Wiley
Date: 02-1994
DOI: 10.1111/J.1600-0609.1994.TB01290.X
Abstract: The efficacy and toxicity of a regimen consisting of amsacrine (m-AMSA), cytarabine, and thioguanine for remission-induction therapy in poor prognosis categories of acute myeloid leukaemia (AML) were determined in a single arm study of 46 patients. The study group consisted of 17 patients with disease refractory to daunorubicin plus cytarabine-based induction regimens, 22 patients with disease which had relapsed during daunorubicin plus cytarabine maintenance therapy, or following completion of this maintenance programme after receiving > or = 500 mg daunorubicin/m2, and 7 previously untreated patients where cardiac disease contraindicated anthracycline therapy. Complete remission (CR) was attained in 46%, and probability of survival was comparable to published results for first-line treatment with daunorubicin plus cytarabine regimens. There was no statistically significant difference in CR rate or probability of survival between these three categories of poor prognosis AML, and cardiotoxic complications were uncommon despite extensive anthracycline exposure in the majority. In the 43% of patients who were 60-76 years of age, there was no statistically significant difference in CR rate or probability of survival relative to patients or = 60 years of age.
Publisher: Springer Science and Business Media LLC
Date: 30-10-2020
DOI: 10.1007/S41781-020-00041-Z
Abstract: We describe a method to obtain point and dispersion estimates for the energies of jets arising from b quarks produced in proton–proton collisions at an energy of $$\\sqrt{s}=13\\,\\text {TeV} $$ s = 13 TeV at the CERN LHC. The algorithm is trained on a large s le of simulated b jets and validated on data recorded by the CMS detector in 2017 corresponding to an integrated luminosity of 41 $$\\,\\text {fb}^{-1}$$ fb - 1 . A multivariate regression algorithm based on a deep feed-forward neural network employs jet composition and shape information, and the properties of reconstructed secondary vertices associated with the jet. The results of the algorithm are used to improve the sensitivity of analyses that make use of b jets in the final state, such as the observation of Higgs boson decay to $$\\hbox {b}\\bar{\\hbox {b}}$$ b b ¯ .
Publisher: Springer Science and Business Media LLC
Date: 05-2020
DOI: 10.1140/EPJC/S10052-020-7858-1
Abstract: A measurement is presented of differential cross sections for t -channel single top quark and antiquark production in proton–proton collisions at a centre-of-mass energy of 13 $$\\,\\text {Te}\\text {V}$$ Te by the CMS experiment at the LHC. From a data set corresponding to an integrated luminosity of 35.9 $$\\,\\text {fb}^{-1}$$ fb - 1 , events containing one muon or electron and two or three jets are analysed. The cross section is measured as a function of the top quark transverse momentum ( $$p_{\\mathrm{T}} $$ p T ), rapidity, and polarisation angle, the charged lepton $$p_{\\mathrm{T}} $$ p T and rapidity, and the $$p_{\\mathrm{T}} $$ p T of the $$\\text {W}{}{}$$ W boson from the top quark decay. In addition, the charge ratio is measured differentially as a function of the top quark, charged lepton, and $$\\text {W}{}{}$$ W boson kinematic observables. The results are found to be in agreement with standard model predictions using various next-to-leading-order event generators and sets of parton distribution functions. Additionally, the spin asymmetry, sensitive to the top quark polarisation, is determined from the differential distribution of the polarisation angle at parton level to be $$0.440 \\pm 0.070$$ 0.440 ± 0.070 , in agreement with the standard model prediction.
Publisher: American Physical Society (APS)
Date: 30-11-2020
Publisher: Springer Science and Business Media LLC
Date: 06-2020
Publisher: Elsevier BV
Date: 08-1968
DOI: 10.1016/0006-291X(68)90674-8
Abstract: The neuroprotective effects of Licochalcone A (Lico.A), a flavonoid isolated from the herb licorice, in Parkinson's disease (PD) have not been elucidated. The prominent pathological feature of PD is the loss of dopaminergic neurons. The crucial role of neuroinflammation induced by activated microglia in dopaminergic neurodegeneration has been validated. In this study, we explore the therapeutic effects of Lico.A in lipopolysaccharide (LPS)-induced PD models in vivo and in vitro. We find that Lico.A significantly inhibits LPS-stimulated production of pro-inflammatory mediators and microglial activation by blocking the phosphorylation of extracellular signal-regulated kinase (ERK1/2) and nuclear factor κB (NF-κB) p65 in BV-2 cells. In addition, through cultured primary mesencephalic neuron-glia cell experiments, we illustrate that Lico.A attenuates the decrease in [³H] dopamine (DA) uptake and the loss of tyrosine hydroxylase-immunoreactive (TH-ir) neurons in LPS-induced PD models in vitro. Furthermore, LPS intoxication in rats results in microglial activation, dopaminergic neurodegeneration and significant behavioral deficits in vivo. Lico.A treatment prevents microglial activation and reduction of dopaminergic neuron and ameliorates PD-like behavioral impairments. Thus, these results demonstrate for the first time that the neuroprotective effects of Lico.A are associated with microglia and anti-inflammatory effects in PD models.
Publisher: American Physical Society (APS)
Date: 30-11-2020
Publisher: Elsevier BV
Date: 1982
Publisher: Elsevier BV
Date: 03-2018
Publisher: American Physical Society (APS)
Date: 19-08-2020
Publisher: American Physical Society (APS)
Date: 07-12-2020
Publisher: Wiley
Date: 02-1978
Publisher: Therapeutic Guidelines Limited
Date: 12-2009
Publisher: Therapeutic Guidelines Limited
Date: 07-1997
Publisher: Springer Science and Business Media LLC
Date: 06-2020
Publisher: Wiley
Date: 02-1987
DOI: 10.1111/J.1445-5994.1987.TB05061.X
Abstract: The Atlantic bottlenose dolphin has attracted attention due to the evident impact that environmental stressors have taken on its health. In order to better understand the mechanisms linking environmental health with dolphin health, we have established cell cultures from dolphin skin as in vitro tools for molecular evaluations. The vitamin D3 pathway is one mechanism of interest because of its well established chemopreventative and immunomodulatory properties in terrestrial mammals. On the other hand, little is known of the physiological role of this molecule in aquatic animals. 1,25-dihydroxyvitamin D3 (1,25D3), the bioactive and hormonal form of vitamin D3, exerts its biological function by binding to the vitamin D receptor (VDR), a ligand-activated regulator of gene transcription. Therefore, we investigated the transcriptomic changes induced by 1,25D3 administration in dolphin skin cells. Identification of specific genes activated by 1,25D3 has provided clues to the physiological function of the vitamin D3 pathway in the dolphin. We found that exposure of the cells to 1,25D3 upregulated transactivation of a vitamin D-sensitive promoter. cDNA microarray analysis, using a novel dolphin array, identified specific gene targets within this pathway, and real-time PCR (qPCR) confirmed the enhanced expression of select genes of interest. These transcriptional changes correlated with an increase in VDR levels. This is the first report of the presence and activation of the vitamin D3 pathway in a marine mammal, and our experimental results demonstrate a number of similarities to terrestrial animals. Conservation of this pathway in the Atlantic bottlenose dolphin is consistent with the importance of nonclassic functions of vitamin D3, such as its role in innate immunity, similar to what has been demonstrated in other mammals.
Publisher: Elsevier BV
Date: 1984
Publisher: American Society of Hematology
Date: 15-11-2022
Publisher: AMPCo
Date: 12-1979
DOI: 10.5694/J.1326-5377.1979.TB104268.X
Abstract: Recognition of needle-like crystals in the cornea of a patient with deteriorating visual acuity initiated laboratory studies which demonstrated underlying multiple myeloma. Crystal deposition in the cornea occurs only rarely in multiple myeloma, and evidently reflects an unusual tendency for certain paraproteins to form numerous small aggregates which are deposited particularly within, and between, corneal epithelial cells. Treatment with chemotherapy, plus repeated plasma exchange with a normal plasma protein product resulted in significant depletion of crystals, and improvement in visual acuity over a period of three weeks. Accelerated clearance of paraprotein by plasmapheresis appeared to contribute materially to the rapidity of recovery, since recovery was considerably faster than in reported cases where treatment was with chemotherapy alone.
Publisher: Wiley
Date: 02-1985
DOI: 10.1111/J.1445-5994.1985.TB02756.X
Abstract: Neutropenia is a life-threatening sequel of hematological disorders and a dominant factor limiting the dosage of cytotoxic chemotherapy. The role of the neutrophil is of such importance in defence against microbial invasion that measures that modify the behaviour of residual hemopoietic tissue to promote a modest increase in neutrophils, can confer considerable benefit by reducing the frequency and severity of infection. Such a change can be mediated in bone marrow depression by ersion of more progeny of immature precursors into the neutrophil series, or by enhancement of the stimulatory drive operating on neutrophil production. The former effect can be achieved by hypertransfusion of red cells to reduce the demand on the limited precursor population for cells of the erythroid series. The latter effect can be achieved by administration of lithium carbonate. Neutropenia caused by autoimmune injury to the neutrophil series can also be successfully modified by measures which suppress the underlying immune dyscrasia or the function of the reticulo-endothelial system. Corticosteroid administration and splenectomy can be helpful in certain specific types of neutropenia. Administration of cyclophosphamide and azathioprine has both mutagenic and marrow suppressive potential, but can induce remissions in severe chronic isolated neutropenia and in systemic lupus erythematosis.
Publisher: IOP Publishing
Date: 07-2021
DOI: 10.1088/1748-0221/16/07/P07001
Abstract: The muon trigger system of the CMS experiment uses a combination of hardware and software to identify events containing a muon. During Run 2 (covering 2015–2018) the LHC achieved instantaneous luminosities as high as 2 × 10 34 while delivering proton-proton collisions at √(s) = 13. The challenge for the trigger system of the CMS experiment is to reduce the registered event rate from about 40MHz to about 1kHz. Significant improvements important for the success of the CMS physics program have been made to the muon trigger system via improved muon reconstruction and identification algorithms since the end of Run 1 and throughout the Run 2 data-taking period. The new algorithms maintain the acceptance of the muon triggers at the same or even lower rate throughout the data-taking period despite the increasing number of additional proton-proton interactions in each LHC bunch crossing. In this paper, the algorithms used in 2015 and 2016 and their improvements throughout 2017 and 2018 are described. Measurements of the CMS muon trigger performance for this data-taking period are presented, including efficiencies, transverse momentum resolution, trigger rates, and the purity of the selected muon s le. This paper focuses on the single- and double-muon triggers with the lowest sustainable transverse momentum thresholds used by CMS. The efficiency is measured in a transverse momentum range from 8 to several hundred.
Publisher: Wiley
Date: 08-2012
DOI: 10.1111/J.1445-5994.2012.02852.X
Abstract: Experience in the treatment of patients with acute promyelocytic leukaemia (APL) and accelerated phase chronic myeloid leukaemia with orally administered arsenic trioxide (ATO) in our institution since 1999 has demonstrated that bioavailability of oral ATO is comparable with intravenous administration, and similar outcomes are produced in treatment of APL. Oral administration was well tolerated, with good compliance, in patients not requiring hospitalisation for postinduction treatment and was particularly convenient for patients living considerable distances from our institution. Orally administered ATO can be considered a practicable option in management of APL.
Publisher: Wiley
Date: 09-1988
DOI: 10.1111/J.1600-0609.1988.TB01183.X
Abstract: Remissions occurred in 2 of 5 consecutive cases of acquired pure red cell aplasia (PRCA) during an initial course of treatment with either azathioprine and prednisolone, or cyclophosphamide and prednisolone. Crossover to therapy with the alternative cytotoxic immunosuppressive agent in conjunction with continued administration of prednisolone in 3 unresponsive cases resulted in remission induction. Crossover to azathioprine was effective in 2 cases initially unresponsive to cyclophosphamide, and crossover to cyclophosphamide in 1 initially unresponsive to azathioprine. This emphasises that lack of cross-resistance to these drugs can occur in PRCA, and that crossover to treatment with the alternative agent in refractory cases is a useful strategy which has been underutilised in reported approaches to management. Administration of the effective regimen was continued for a mean of 15 months, and this more extended period of treatment was associated with a longer mean duration of remission than reported in previous studies.
Publisher: Wiley
Date: 10-1996
DOI: 10.1046/J.1365-2141.1996.D01-1868.X
Abstract: Thirty-five patients (eight de novo, 27 relapsed disease) with low-grade non-Hodgkin's lymphoma (diffuse small lymphocytic, follicular small cleaved cell, follicular mixed cell, and lymphoplasmacytoid) were treated with 2-chlorodeoxyadenosine (2CdA) at a daily dose of 0.14 mg/kg for 5d (2 h infusion) for an average of three cycles. Minor treatment delays, generally due to haematological toxicities, occurred in nine of 105 cycles. Major toxicities were lymphopenia, neutropenia and thrombocytopenia. Opportunistic infections occurred in seven patients. Overall response rate was 69% (five complete, 19 partial) reaching 88% for de novo patients (two complete, five partial). Elevated beta 2-microglobulin level was negatively predictive of response (P = 0.0014). Eight of 24 responders relapsed, with a median follow-up of 13 months. 2CdA administered as an intermittent infusion shows considerable single-agent activity in low-grade lymphomas achieving high response rates of prolonged duration. Consideration of schedules where 2CdA is alternatively administered with combination chemotherapy appears warranted.
Publisher: Wiley
Date: 11-12-2020
DOI: 10.1111/EJH.13340
Publisher: American Society of Hematology
Date: 05-1980
Publisher: Elsevier BV
Date: 1982
Publisher: Elsevier BV
Date: 10-2020
Publisher: Elsevier BV
Date: 09-2015
Publisher: Springer Science and Business Media LLC
Date: 07-2020
DOI: 10.1140/EPJC/S10052-020-7917-7
Abstract: Normalised multi-differential cross sections for top quark pair ( $$\\hbox {t}{\\bar{\\hbox {t}}}$$ t t ¯ ) production are measured in proton-proton collisions at a centre-of-mass energy of 13 $$\\,{\\text {TeV}}$$ TeV using events containing two oppositely charged leptons. The analysed data were recorded with the CMS detector in 2016 and correspond to an integrated luminosity of $$35.9{\\,{\\text {fb}}^{-1}} $$ 35.9 fb - 1 . The double-differential $$\\hbox {t}{\\bar{\\hbox {t}}}$$ t t ¯ cross section is measured as a function of the kinematic properties of the top quark and of the $$\\hbox {t}{\\bar{\\hbox {t}}}$$ t t ¯ system at parton level in the full phase space. A triple-differential measurement is performed as a function of the invariant mass and rapidity of the $$\\hbox {t}{\\bar{\\hbox {t}}}$$ t t ¯ system and the multiplicity of additional jets at particle level. The data are compared to predictions of Monte Carlo event generators that complement next-to-leading-order (NLO) quantum chromodynamics (QCD) calculations with parton showers. Together with a fixed-order NLO QCD calculation, the triple-differential measurement is used to extract values of the strong coupling strength $$\\alpha _{S}$$ α S and the top quark pole mass ( $$m_{{\\text {t}}}^{{\\text {pole}}}$$ m t pole ) using several sets of parton distribution functions (PDFs). The measurement of $$m_{{\\text {t}}}^{{\\text {pole}}}$$ m t pole exploits the sensitivity of the $$\\hbox {t}{\\bar{\\hbox {t}}}$$ t t ¯ invariant mass distribution to $$m_{{\\text {t}}}^{{\\text {pole}}}$$ m t pole near the production threshold. Furthermore, a simultaneous fit of the PDFs, $$\\alpha _{S}$$ α S , and $$m_{{\\text {t}}}^{{\\text {pole}}}$$ m t pole is performed at NLO, demonstrating that the new data have significant impact on the gluon PDF, and at the same time allow an accurate determination of $$\\alpha _{S}$$ α S and $$m_{{\\text {t}}}^{{\\text {pole}}}$$ m t pole . The values $$\\alpha _{S}(m_{{\\text {Z}}}) = 0.1135{}^{+0.0021}_{-0.0017}$$ α S ( m Z ) = 0.1135 - 0.0017 + 0.0021 and $$m_{{\\text {t}}}^{{\\text {pole}}} = 170.5 \\pm 0.8 \\,{\\text {GeV}} $$ m t pole = 170.5 ± 0.8 GeV are extracted, which account for experimental and theoretical uncertainties, the latter being estimated from NLO scale variations. Possible effects from Coulomb and soft-gluon resummation near the $$\\hbox {t}{\\bar{\\hbox {t}}}$$ t t ¯ production threshold are neglected in these parameter extractions. A rough estimate of these effects indicates an expected correction of $$m_{{\\text {t}}}^{{\\text {pole}}}$$ m t pole of the order of $$+1 \\,{\\text {GeV}} $$ + 1 GeV , which can be regarded as additional theoretical uncertainty in the current $$m_{{\\text {t}}}^{{\\text {pole}}}$$ m t pole extraction.
Publisher: Elsevier BV
Date: 02-2005
Publisher: Wiley
Date: 02-2009
DOI: 10.1111/J.1756-5391.2009.01008.X
Abstract: First published in 2001, STRICTA (STandards for Reporting Interventions in Controlled Trials of Acupuncture) was designed to expand on the reporting of one item within the CONSORT (Consolidated Standards of Reporting Trials) Statement checklist, the item relating to the intervention. Two recent reviews had found that STRICTA was highly regarded in the field and that there was a need for minor revisions. To revise STRICTA within the CONSORT family of reporting guidelines. A collaborative effort involving the STRICTA Group, the CONSORT Group and the Chinese Cochrane Centre was agreed. A consultation process with 47 international experts provided detailed feedback on an initial draft of a revised checklist. These data, along with the two review studies, comprised the documentation for a consensus meeting in Freiburg, Germany in October 2008. A total of 21 participants attended the meeting, bringing their expertise as research methodologists, reporting guideline developers, acupuncturists, physicians and journal editors. At the workshop, a revised draft checklist was agreed. There was general consensus that STRICTA should continue to function as a stand-alone guideline as well as an extension to CONSORT. It was agreed that STRICTA should be sufficiently broad to cover all type of clinical studies, from case reports through uncontrolled studies to randomised controlled trials. It was also decided that explanations and ex les, as with other CONSORT reporting guidelines, would provide a useful way of supporting the uptake to the new recommendations when published. The checklist will be subjected to further revision processes in order to further its impact and support wider dissemination. Journals that regularly publish acupuncture trials will be encouraged to adopt the revised STRICTA, include it in their guidelines for authors, and promote the adoption of its recommendations for clinical studies of acupuncture.
Publisher: Wiley
Date: 05-1987
Abstract: Severe neutropenia due to selective loss from the bone marrow of cells of the entire neutrophil maturation sequence developed in a patient with Goodpasture's Syndrome and was associated with serious infections complicating continuous ambulatory peritoneal dialysis. Involvement of T-lymphocytes in the process affecting the neutrophil series was implicated by the relation between recovery from neutropenia and treatment with antithymocyte globulin (ATG). Azathioprine and corticosteroid administration failed to sustain recovery from neutropenia induced by ATG. It is concluded that ATG can provide a nonmyelotoxic form of therapy for pure white cell aplasia whose effectiveness is independent of responsiveness to other immunosuppressive agents.
Publisher: Springer Science and Business Media LLC
Date: 04-2020
Publisher: Springer Science and Business Media LLC
Date: 05-2020
Publisher: Wiley
Date: 10-1974
DOI: 10.1111/J.1445-5994.1974.TB03218.X
Abstract: In cancer patients treated for venous thromboembolism (VTE), including deep-vein thrombosis (DVT) and pulmonary embolism (PE), analyzing mortality associated with recurrent VTE or major bleeding is needed to determine the optimal duration of anticoagulation.This was a cohort study using the Registro Informatizado de Enfermedad TromboEmbólica (RIETE) Registry database to compare rates of fatal recurrent PE and fatal bleeding in cancer patients receiving anticoagulation for VTE.As of January 2013, 44,794 patients were enrolled in RIETE, of whom 7911 (18%) had active cancer. During the course of anticoagulant therapy (mean, 181 ± 210 days), 178 cancer patients (4.3%) developed recurrent PE (5.5 per 100 patient-years 95% CI: 4.8-6.4), 194 (4.7%) had recurrent DVT (6.2 per 100 patient-years 95% confidence interval [CI]: 5.3-7.1), and 367 (8.9%) bled (11.3 per 100 patient-years 95% CI: 10.2-12.5). Of 4125 patients initially presenting with PE, 43 (1.0%) died of recurrent PE and 45 (1.1%) of bleeding of 3786 patients with DVT, 19 (0.5%) died of PE, and 55 (1.3%) of bleeding. During the first 3 months of anticoagulation, there were 59 (1.4%) fatal PE recurrences and 77 (1.9%) fatal bleeds. Beyond the third month, there were 3 fatal PE recurrences and 23 fatal bleeds.In RIETE cancer patients, the rate of fatal recurrent PE or fatal bleeding was much higher within the first 3 months of anticoagulation therapy.
Publisher: Springer Science and Business Media LLC
Date: 05-2020
Publisher: Wiley
Date: 02-1977
DOI: 10.1111/J.1365-2141.1977.TB00579.X
Abstract: The response of granulopoietic activity in bone marrow depression to a reduction in the demand for erythropoiesis has been examined by means of hypertransfusing C-57B mice which had been exposed to sublethal whole body irradiation. Multiple intraperitoneal injections of 0.5 ml packed red cells from irradiated donors were employed to maintain the haematocrit sufficiently above the normal range to produce significant suppression of erythropoietic activity for the duration of the bone marrow depression. This was associated with elevation above control values of 32--102% in the blood granulocyte count, 22--78% in total cells of the granulocytic series per femur, and up to 44% in total agar colony forming units per femur. Restoration of essentially normal values occurred 13 d after irradiation in contrast to 17--18 d in controls. Single transfusions which produced less suppression of erythroblast numbers per femur resulted in an intermediate degree of improvement in these parameters. Such changes in the granulocyte compartment indicate improved granulopoietic capacity in the hypertransfused group. It is suggested that this effect reflects increased production of granulocyte progenitors due to the reduction in competing demands on the compromised multipotential stem cell compartment for progenitors of the erythroid series. The findings raise the possibility that hypertransfusion might be capable of producing a beneficial effect on granulopoiesis in human bone marrow depression.
Publisher: IOP Publishing
Date: 20-08-2020
Publisher: Wiley
Date: 10-1979
DOI: 10.1111/J.1365-2141.1979.TB03742.X
Abstract: Electron microscopic examination was carried out on mitochondrial DNA molecules isolated from leucocytes in seven cases of acute leukaemia or leukaemic-phase poorly-differentiated lymphocytic lymphoma. There was a marked shift from the predominant circular monomeric form in normal leucocytes to circles with twice the normal circumference, as well as multiple interlocking circles in two of the four cases of untreated acute leukaemia, and in one of untreated lymphoma. This abnormal pattern of mitochondrial DNA evidently reflects an intrinsic aberration in the processing of mitochondrial DNA in some leukaemias and lymphomas, as it occurred in the absence of prior therapy with alkylating agents known to interact with DNA. Up to 47% of total mitochondrial DNA was present in such complex forms, which on steric grounds should be unsuitable as a template for replication of free monomers and possibly for messenger RNA production. The latter may be pertinent to previously reported abnormalities in acute leukaemia leucocytes which could be related to abnormal production of gene products of mitochondrial DNA.
Publisher: American Physical Society (APS)
Date: 03-09-2020
Publisher: IOP Publishing
Date: 05-05-2020
Publisher: Springer Science and Business Media LLC
Date: 12-2020
Abstract: A search for standard model Higgs bosons (H) produced with transverse momentum ( p T ) greater than 450 GeV and decaying to bottom quark-antiquark pairs ( $$ \\mathrm{b}\\overline{\\mathrm{b}} $$ b b ¯ ) is performed using proton-proton collision data collected by the CMS experiment at the LHC at $$ \\sqrt{s} $$ s = 13 TeV. The data s le corresponds to an integrated luminosity of 137 fb − 1 . The search is inclusive in the Higgs boson production mode. Highly Lorentz-boosted Higgs bosons decaying to $$ \\mathrm{b}\\overline{\\mathrm{b}} $$ b b ¯ are reconstructed as single large-radius jets, and are identified using jet substructure and a dedicated b tagging technique based on a deep neural network. The method is validated with Z → $$ \\mathrm{b}\\overline{\\mathrm{b}} $$ b b ¯ decays. For a Higgs boson mass of 125 GeV, an excess of events above the background assuming no Higgs boson production is observed with a local significance of 2.5 standard deviations ( σ ), while the expectation is 0.7. The corresponding signal strength and local significance with respect to the standard model expectation are μ H = 3 . 7 ± 1 . 2(stat) $$ {}_{-0.7}^{+0.8} $$ − 0.7 + 0.8 (syst) $$ {}_{-0.5}^{+0.8} $$ − 0.5 + 0.8 (theo) and 1 . 9 σ . Additionally, an unfolded differential cross section as a function of Higgs boson p T for the gluon fusion production mode is presented, assuming the other production modes occur at the expected rates.
Publisher: Wiley
Date: 10-1980
DOI: 10.1002/1097-0142(19801001)46:7<1657::AID-CNCR2820460727>3.0.CO;2-A
Abstract: A case of adenocarcinoma of the bile duct complicating longstanding ulcerative colitis and associated with the rapid onset and growth of multiple seborrheic keratosis (Leser-Trelat sign) and pure red blood cell aplasia is described. This is the first report of a case of the coexistence of the Leser-Trelat sign and pure red blood cell aplasia in a patient with a malignancy. Both manifestations have been doubted as truly paraneoplastic manifestations because of their rarity in clinical medicine. Their co-existence in the present case would support their associaton with malignancy.
Publisher: American Society of Hematology
Date: 24-12-2020
Abstract: Warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndrome is a rare primary immunodeficiency caused by gain-of-function mutations in the CXCR4 gene. We report the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy of mavorixafor from a phase 2 open-label dose-escalation and extension study in 8 adult patients with genetically confirmed WHIM syndrome. Mavorixafor is an oral small molecule selective antagonist of the CXCR4 receptor that increases mobilization and trafficking of white blood cells from the bone marrow. Patients received escalating doses of mavorixafor, up to 400 mg once daily. Five patients continued on the extension study for up to 28.6 months. Mavorixafor was well tolerated with no treatment-related serious adverse events. At a median follow-up of 16.5 months, we observed dose-dependent increases in absolute neutrophil count (ANC) and absolute lymphocyte count (ALC). At doses ≥300 mg/d, ANC was maintained at & cells per microliter for a median of 12.6 hours, and ALC was maintained at & cells per microliter for up to 16.9 hours. Continued follow-up on the extension study resulted in a yearly infection rate that decreased from 4.63 events (95% confidence interval, 3.3-6.3) in the 12 months prior to the trial to 2.27 events (95% confidence interval, 1.4-3.5) for patients on effective doses. We observed an average 75% reduction in the number of cutaneous warts. This study demonstrates that mavorixafor, 400 mg once daily, mobilizes neutrophil and lymphocytes in adult patients with WHIM syndrome and provides preliminary evidence of clinical benefit for patients on long-term therapy. The trial was registered at www.clinicaltrials.gov as #NCT03005327.
Publisher: Springer Science and Business Media LLC
Date: 11-2020
Abstract: Decays of the 125 GeV Higgs boson into a Z boson and a ρ 0 (770) or ϕ(1020) meson are searched for using proton-proton collision data collected by the CMS experiment at the LHC at $$ \\sqrt{s} $$ s = 13 TeV. The analysed data set corresponds to an integrated luminosity of 137 fb − 1 . Events are selected in which the Z boson decays into a pair of electrons or a pair of muons, and the ρ and ϕ mesons decay into pairs of pions and kaons, respectively. No significant excess above the background model is observed. As different polarization states are possible for the decay products of the Z boson and ρ or ϕ mesons, affecting the signal acceptance, scenarios in which the decays are longitudinally or transversely polarized are considered. Upper limits at the 95% confidence level on the Higgs boson branching fractions into Zρ and Zϕ are determined to be 1.04–1.31% and 0.31–0.40%, respectively, where the ranges reflect the considered polarization scenarios these values are 740–940 and 730–950 times larger than the respective standard model expectations. These results constitute the first experimental limits on the two decay channels.
Publisher: Springer Science and Business Media LLC
Date: 12-2020
Abstract: The dependence of inclusive jet production in proton-proton collisions with a center-of-mass energy of 13 TeV on the distance parameter R of the anti- k T algorithm is studied using data corresponding to integrated luminosities up to 35.9 fb − 1 collected by the CMS experiment in 2016. The ratios of the inclusive cross sections as functions of transverse momentum p T and rapidity y , for R in the range 0.1 to 1.2 to those using R = 0 . 4 are presented in the region 84 p T 1588 GeV and | y | 2 . 0. The results are compared to calculations at leading and next-to-leading order in the strong coupling constant using different parton shower models. The variation of the ratio of cross sections with R is well described by calculations including a parton shower model, but not by a leading-order quantum chromodynamics calculation including nonperturbative effects. The agreement between the data and the theoretical predictions for the ratios of cross sections is significantly improved when next-to-leading order calculations with nonperturbative effects are used.
Publisher: Springer Science and Business Media LLC
Date: 08-2020
DOI: 10.1140/EPJC/S10052-020-8166-5
Abstract: Central exclusive and semiexclusive production of "Equation missing" pairs is measured with the CMS detector in proton-proton collisions at the LHC at center-of-mass energies of 5.02 and 13TeV. The theoretical description of these nonperturbative processes, which have not yet been measured in detail at the LHC, poses a significant challenge to models. The two pions are measured and identified in the CMS silicon tracker based on specific energy loss, whereas the absence of other particles is ensured by calorimeter information. The total and differential cross sections of exclusive and semiexclusive central "Equation missing" production are measured as functions of invariant mass, transverse momentum, and rapidity of the "Equation missing" system in the fiducial region defined as transverse momentum "Equation missing" and pseudorapidity "Equation missing" . The production cross sections for the four resonant channels "Image missing" , "Equation missing" , "Image missing" , and "Image missing" are extracted using a simple model. These results represent the first measurement of this process at the LHC collision energies of 5.02 and 13TeV.
Publisher: American Society of Hematology
Date: 06-12-2014
DOI: 10.1182/BLOOD.V124.21.2730.2730
Abstract: Background: In 1994 Severe Chronic Neutropenia International Registry (SCNIR) opened for enrollment of patients with at least 3 absolute neutrophil counts (ANC) less than 0.5 x 109/L during a three month period. At that time severe chronic neutropenia (SCN) was categorized as cyclic, congenital, autoimmune or idiopathic based largely on clinical criteria. A randomized trial had established effectiveness of treatment with granulocyte colony-stimulating factor (G-CSF), but long-term consequences of such treatment were unknown. Hypothesis: We began the SCNIR based on the hypothesis that underlying pathophysiology, natural history of patients with chronic neutropenia and benefits and risk of G-CSF therapy could only be accurately established through an international registry with long term follow-up of patients with these rare hematological disorders. Methods: SCNIR enrollment requires informed consent, ANC .5 x 109/L at least 3 times over a 3 month period, neutropenia not due to known systemic autoimmune disease (e.g., lupus, rheumatoid arthritis), cancer or cancer chemotherapy. There is a centralized enrollment process directed through offices in the US (Seattle) and Germany (Hannover). Continued enrollment requires annual follow-up information, i.e., clinical status, treatments and blood counts, and bone marrow reports for some categories of patients. Data on pregnancies, stem cell transplantation (SCT), non-hematological features and complications are also collected on standardized forms for subsets of patients. Comprehensive immunological assessments and genetic testing are encouraged but not required for enrollment. For some patient groups, e.g., Shwachman-Diamond syndrome (SDS) and Barth syndrome, the SCNIR now enrolls patients without severe neutropenia to gain perspectives on long-term outcomes for these disorders. Since 1994 the SCNIR has enrolled more than 2000 patients 174 died, 193 resolved neutropenia, 543 withdrew or were lost to follow-up and almost all others continue in this long term observation study. The median follow-up for enrolled patients is now almost 10 years. The most common patient categories are idiopathic, cyclic (CyN) and congenital neutropenia (CN) 68% of CyN and 65% of CN patients having sequencing studies have mutations in ELANE. Some specific mutations are associated with high frequency ( %) of severe outcomes (e.g. MDS/AML, failure to respond to G-CSF, death from infections, need for stem cell transplant) often many years after SCNIR enrollment and beginning G-CSF therapy. GSD1 patients improve with G-CSF treatment, but experience splenomegaly and continued problems with infections or complications. The SCNIR through a SDS sub-registry is redefining Shwachman-Diamond syndrome only about one-half of enrollees have “classic” presentation and a substantial number with “classic presentation” lack mutations in SBDS. The SCNIR is participating in an NIH trial of a CXCR4 antagonist for treatment of WHIM syndrome, as an ex le of molecularly targeted treatment for this rare disease. The SCNIR is also the key resource for discovery of genetic causes for congenital neutropenia, e.g., G6PC3, HAX1, and TCIRG1 and others, recognition of differences in frequency of autosomal dominant and recessive SCN in populations of Europe and North America and identifying congenital neutropenia cases of unknown cause. Genetic testing has also broadened the clinical spectrum of these disorders. Conclusions: Through the efforts of patients, families, physicians, nurses and investigators, and with support from the NIH, industry, and private philanthropy, chronic neutropenia is now far better understood at the genetic, molecular and cellular level than 20 years ago. Treatment responses to G-CSF are well characterized novel therapies are emerging and the prognosis for patients with SCN appears to be improving. The knowledge gained through the SCNIR and availability of G-CSF has redefined clinicians’ approach to chronic neutropenia. The SCNIR is a model of international research collaboration to understand rare diseases in hematology and other areas of medicine. Broad enrollment criteria, physician, patient and family participation, a dedicated staff, and continuing cooperation underlie success of the SCNIR and this model to understanding rare diseases. Dale: Amgen: Consultancy, Honoraria, Research Funding. Boxer:Amgen: Equity Ownership. Morrow:Amgen: Employment.
Publisher: Wiley
Date: 09-1996
DOI: 10.1046/J.1365-2141.1996.D01-1819.X
Abstract: The incidence of hypercalcaemia and its association with humoral mechanisms involving parathyroid hormone-related protein (PTHrP), parathyroid hormone (PTH), or 1.25(OH)2 vitamin D were assessed in a prospective study of patients admitted to a clinical haematology unit. Hypercalcaemia was detected in 18/165 patients, and was due to primary hyperparathyroidism in 3/17 patients in whom results of humoral mediator assessments were obtained. In the other patients, hypercalcaemia was associated in nine instances with myeloma, in five with B-cell non-Hodgkin's lymphoma (NHL), and in one with myeloid neoplasia. No evidence was obtained of a humoral mechanism involving 1.25(OH)2 vitamin D, but elevated circulating levels of PTHrP, comparable with those in humoral hypercalcaemia of malignancy, were present in 2/4 patients with NHL, and in 3/9 with myeloma. The relationship between presence or absence of elevated circulating PTHrP, and presence or absence of hypercalcaemia during the course of treatment, indicated PTHrP was involved in the production of hypercalcaemia. Such an association raises the possibility that PTHrP released by neoplastic cells in these disorders acts in a paracrine manner to produce local bone resorption, and when produced in greater amounts causes elevated circulating levels which make an additional humorally-mediated contribution to the development of hypercalcaemia.
Publisher: American Society of Hematology
Date: 29-11-2018
DOI: 10.1182/BLOOD-2018-99-119840
Abstract: Background: WHIM (Warts, Hypogammaglobulinemia, Infections, Myelokathexis) Syndrome is a serious, ultrarare genetic disorder caused by a gain-of-function mutation in CXCR4 that causes profound neutropenia and lymphopenia associated with increased rates of bacterial and viral infections. Long-term sequelae include hearing loss, bronchiectasis, and HPV-associated malignancies. The cancer risk in WHIM patients is estimated at 30% by age 40. There is currently no treatment that addresses the underlying mechanism of disease. G-CSF increases neutrophil counts but does not appear to reduce infection rates use of parenteral gamma globulin has had mixed reports of benefit, but no controlled trials have been reported Plerixafor, a CXCR4 antagonist, has been shown to increase leukocyte counts and reduce infection rates when absolute neutrophil counts (ANC) mm-3 and absolute lymphocyte counts (ALC) mm-3, but is a parenteral agent that must be administered twice daily. X4P-001 is an orally available, allosteric inhibitor of CXCR4 that is being developed to treat WHIM. We report here the PK/PD data from the Phase 2 portion of Phase 2/3 trial X4P-001 MKKA (NCT03005327) in WHIM patients that led to selection of the dose for Phase 3 development. Methods: Study X4P-001 MKKA is a Phase 2/3 study. The primary objective of Ph2 portion was to assess the dose required to achieve a consistent increase in circulating neutrophils and lymphocytes. Adult patients with WHIM syndrome, with documented WHIM-associated genotype, and either ANC mm-3 and/or ALC mm-3 were treated with escalating doses of X4P-001. After at least 5 weeks on a dose, patients were hospitalized overnight for rich PK s ling. At each s ling point ANC and ALC were also determined. An area under the curve for ANC and ALC was calculated using the trapezoidal rule and normalized to AUCs assuming maintenance of the threshold values of 600 mm-3 for ANC and 1000 mm-3 for ALC over 24hr. Dose escalation was permitted for adjusted AUC value cell/hours/μL. AUC values ≥0 were considered as having met the primary objective for Phase 2. Results: Eight patients were enrolled and were evaluable for efficacy. 6 of 8 were female, and the mean (SD) age was 35.5 (13.37). Two patients started treatment with 50 mg, then received, 100, 150, 300 and 400 mg 2 started at 100 and then received 200 and 300 mg 2 started at 200 mg 1 escalated to 300 and 400 mg while the other terminated after 1 week due to an adverse event (AE). Two started at 300 mg and did not escalate. Doses of at least 300 mg/day were needed to achieve success criteria for ANC, while at doses ≥100 mg/day, 50-100% met success criteria for ALC. (Figure 1) Two patients discontinued: 1 due to an AE of grade 1 rash, and 1 voluntarily withdrew. No serious AEs were reported. One patient had unrelated cholecystitis (grade 3). All other AEs were grade 1 or 2. Conclusions: Treatment of WHIM patients with X4P-001 results in meaningful increases in ANC at doses ≥300 mg, and in ALC at doses ≥100 mg per day for at least 5 weeks. These doses are anticipated to be associated with clinically meaningful outcomes in terms of infections and warts. X4P-001 appeared to be safe and well-tolerated at doses of 50-400 mg per day.4 Dale: Athelas, Inc.: Equity Ownership Amgen: Consultancy, Research Funding Sanofi-Aventi: Consultancy, Honoraria Cellerant: Other: Scientific Advisory Board Hospira: Consultancy Prolong: Consultancy Beheringer-Ingelheim: Consultancy Coherus: Consultancy. Hartmann:Cetara: Employment X4P Pharmaceuticals: Consultancy. Brown:Certara: Employment X4P Pharmaceuticals: Consultancy. Ebrahim:X4Pharmaceuticals: Employment. Gorelick:X4 Pharma: Consultancy PIN Pharma: Consultancy Shire: Consultancy NGN Capital: Consultancy, Other: Venture partner IntraBio: Consultancy Zymo Consulting Group LLC: Employment.
Publisher: Elsevier BV
Date: 07-1986
DOI: 10.1016/S0140-6736(86)92511-0
Abstract: Mucinous cystadenoma is a type of mucocele of the appendix that is rarely encountered in clinical practice. Dogmatic consensus on the optimal surgical modus operandi of appendicular mucocele is lacking in the literature and this remains a subject of controversy. There is little agreement with regard to the best procedure (right hemicolectomy versus appendectomy) or the best surgical approach (laparoscopic versus laparotomy). We report the case of a 70-year-old Asian woman from Karachi who presented with pain in the right iliac fossa for 15 days. On physical examination, a mobile and firm mass was palpable in the right iliac fossa. A colonoscopy was performed which showed external compression of the cecum. A biopsy of the mucosa was normal. Computed tomography scan showed a mucocele of the appendix with minimal periappendiceal fat stranding. She underwent an initial diagnostic laparoscopy to evaluate any mucin spillage in the peritoneal cavity. Once no spillage was identified, an open appendectomy was then performed. Intra-operatively, a frozen section of the appendiceal s le was sent to ascertain the need for an extension of surgery to a right hemicolectomy. Absence of any malignancy on the frozen section obviated the need for a surgical extension. The final histopathological examination showed a mucinous cystadenoma of the appendix. The patient was symptom-free at one year after surgery. It is important to distinguish between mucinous cystadenomas and mucinous cystadenocarcinomas. However, this distinction remains elusive in the pre-operative setting. A simple appendectomy using an intra-operative frozen section appears to be a reasonable surgical approach for selected cases with an intact mucocele of the appendix. However, long-term follow-up is warranted in such patients to evaluate the risks of using this approach.
Publisher: IOP Publishing
Date: 28-02-2020
Publisher: Elsevier BV
Date: 2002
DOI: 10.1080/003130201201117945
Abstract: The reported association of glomerular disease with chronic lymphocytic leukaemia (CLL) is rare despite the relative frequency of this type of leukaemia. Hence, we have examined the renal biopsies in three patients with CLL and glomerulonephritis. Renal biopsies were examined by light microscopy, immunofluorescence microscopy and electron microscopy. One of two patients with mild impairment of renal function and an active urinary sediment had ultrastructural features of idiopathic type I membranoproliferative glomerulonephritis (MPGN), and the other had features of fibrillary/ immunotactoid glomerulonephritis with deposits of IgG and C3. One patient with nephrotic syndrome had characteristic electron microscopic appearances of type III MPGN. In all three there was an association with monoclonal gammopathy. The parameters of glomerular damage improved in association with response to drug treatment of the CLL. There is a spectrum of types of MPGN seen in patients with CLL and there appears to be an association with the presence of monoclonal gammopathy. This is the first reported case of type III MPGN in CLL.
Publisher: Informa UK Limited
Date: 28-01-2014
Publisher: Wiley
Date: 06-1999
Publisher: Informa UK Limited
Date: 19-11-2012
Publisher: Informa UK Limited
Date: 1998
DOI: 10.3109/10428199809050909
Abstract: Hypercalcemia is an important complication in multiple myeloma as well as T-cell leukemia/lymphoma, and is moderately common in high and intermediate grade non-Hodgkin's lymphoma. The underlying mechanism has been unclear because the neoplastic cells are usually present in the bone marrow, where they are in a position to produce short range effects on bone resorption which are difficult to identify. This contrasts with the situation in hypercalcemia associated with non-metastatic carcinoma, where it has been clearly demonstrated that the most common cause is release from the tumor of a humoral mediator, Parathyroid Hormone-related Protein (PTHrP). Roles have been advocated in multiple myeloma for release of a number of other cytokines with osteolytic capacity on the basis of their enhancement of osteolytic activity in cultured fetal rat bone, although a causal relationship in patients has not been established. PTHrP has more recently been implicated in the genesis of hypercalcemia in patients with hematological malignancies by the demonstration in a proportion of cases of increased circulating levels of PTHrP, comparable to those in hypercalcemia due to cancer. Immunohistochemical studies indicate neoplastic hemopoietic cells can contain PTHrP, and thus have the capacity to act in a paracrine manner to enhance local bone resorption and contribute to the development of hypercalcemia.
Publisher: Therapeutic Guidelines Limited
Date: 04-2010
Publisher: Therapeutic Guidelines Limited
Date: 04-2010
Publisher: Wiley
Date: 1978
Abstract: The clinical course of a patient with chronic hepatitis and previous ulcerative colitis who subsequently developed pure red cell aplasia (PRCA) is described. The PRCA remitted initially with corticosteroid therapy. A subsequent relapse responded to cyclophosphamide therapy following splenectomy. This was followed by a fatal third episode of red cell aplasia associated with megakaryocyte aplasia.
Publisher: Therapeutic Guidelines Limited
Date: 04-2010
Publisher: Springer Science and Business Media LLC
Date: 06-2020
Publisher: Wiley
Date: 06-1989
DOI: 10.1111/J.1445-5994.1989.TB00262.X
Abstract: Although polymorphic variations in genes of the RAS system have previously been associated with susceptibility to AAA, such studies have been significantly limited by small s le sizes. This study was undertaken, using the largest case series yet reported, to determine whether common genetic variants of the RAS are associated with either susceptibility or severity of AAA. The frequencies of 4 common genetic variants of genes related to the renin-angiotensin system were investigated in 3 geographically distinct, but ethnically similar, case-control cohorts, resulting in comparison of 1226 AAA cases with 1723 controls. In all 3 the AGTR1 1166C allele was significantly more common in AAA patients than controls (overall adjusted OR 1.60, 95% CI 1.32 to 1.93, P=1.1x10(-6)). Overall, the ACE ID genotype was associated with AAA (OR 1.33, 95% CI 1.06 to 1.67, P<0.02). The AGT 268T allele appeared to have an epistatic effect on large aneurysm size. This study has identified a strong and repeated association between the AGTR1 1166C allele and susceptibility to AAA, and a weaker effect associated with the ACE deletion allele, in 3 geographically distinct, but ethnically similar, case-control cohorts. This study highlights the key role of the RAS in AAA and emphasizes the need for replication and validation of results in suitable independent cohorts.
Publisher: Elsevier BV
Date: 1984
DOI: 10.3109/00313028409067912
Abstract: Analysis of the bone marrow karyotype in 109 consecutive untreated patients with acute lymphoblastic leukemia (ALL) by the G-banding technique revealed the presence of a translocation between specific sites on the long arms of chromosomes 4 and 11, [t(4 ) (q21 q23)] in 3 adults and 2 children. Splenomegaly was present in all patients, marked leukocytosis in 4, and retinal hemorrhages in the absence of significant mucocutaneous bleeding in 3. Complete remission defined by conventional morphological criteria was achieved with combination chemotherapy in all instances, but the duration of remission was brief in 3. Three patients were studied in relapse, and clonal evolution was found to have occurred in 2. Analysis of our data in conjunction with other published reports suggests this specific karyotypic abnormality characterizes a small subgroup of ALL in which there is a strong association with recognized clinical and laboratory indices of poor prognosis, in particular its frequent occurrence in children under the age of 2.5 yr. There is a propensity to undergo clonal evolution, and the possibility exists that such a development is associated with poor prognosis.
Publisher: Wiley
Date: 2198
DOI: 10.1111/J.1445-5994.1980.TB03714.X
Abstract: A case is described in which polycythaemia vera was found to co-exist with chronic lymphatic leukaemia at the time of presentation. This case can be added to five other reported cases of an association between polycythaemia vera and well-differentiated lymphocytic neoplasia, and adds further emphasis to the tendency for dual presentation, which has now occurred in all but one of these cases. One explanation is that the association is due to chance, but the tendency for dual presentation raises the possibility that the overall picture reflects neoplastic involvement of stem cells with capacity to differentiate into the lymphoid as well as the erythroid, myeloid and megakaryocytic series.
Publisher: IOP Publishing
Date: 03-06-2020
Publisher: Informa UK Limited
Date: 15-05-2013
Publisher: American Society of Hematology
Date: 06-12-2014
DOI: 10.1182/BLOOD.V124.21.375.375
Abstract: BACKGROUND The combination of ATRA and anthracycline-based chemotherapy has traditionally been regarded as the gold standard for induction and consolidation in previously untreated APL patients (pts), with ATO usually reserved for relapse. Recent data in Sanz low-risk (LR) and intermediate-risk (IR) APL indicate ATRA + ATO is superior to ATRA + chemotherapy (N Engl J Med 2013), but the optimal therapy for high-risk (HiR) pts remains unclear. In an attempt to improve anti-leukemic efficacy whilst limiting reliance on anthracyclines for all risk categories of APL, the ALLG incorporated ATO into an ATRA + reduced chemotherapy backbone, and the results of an interim analysis with a median follow-up of 2 years (yr) have been published (Blood 120:1570, 2012). Herein, we report results of the protocol-specified final analysis, conducted when all surviving pts had been followed for at least 2 yr after completion of consolidation. METHODS As published, APML4 protocol treatment comprised: (i) induction with ATRA (45 mg/m2 d1-36), IDA (12 mg/m2 d2,4,6,8), ATO (0.15 mg/kg d9-36), prophylactic prednisone (1 mg/kg d1-10) and aggressive hemostatic support (ii) consolidation with ATRA and ATO (continuous in cycle 1, intermittent in cycle 2) (iii) 2 yr oral maintenance with ATRA, 6-mercaptopurine and methotrexate. Between 2004-2009, 124 evaluable pts were accrued, and median follow-up by the censor-reversing Kaplan-Meier method in this final analysis is 4.2 yr. RESULTS Median age was 44 (3-78) yr, median white cell count was 2.4 x 109/L (0.1-85.8), and median platelet count 22 x 109/L (2-173). Risk groups were 33 LR, 67 IR, 23 HiR, 1 unknown. FLT3 mutations were present in 44%, and 11% had ≥ 2 additional cytogenetic abnormalities (2+ACA). There were 4 (3.2%) deaths during induction (myocardial infarction d1, cerebral hemorrhage d3 and d7, cerebral edema and seizures d30). Grade 3-4 non-hematological adverse events included differentiation syndrome in 14%, and frequent but reversible biochemical hepatic and gastrointestinal toxicity. Q-Tc prolongation 500 msec occurred in 14%, but there were no cases of ventricular arrhythmias or torsades de pointe. Significant neurological and cutaneous toxicity were infrequent. After induction, 118 pts (95%) achieved hematological complete remission 112 commenced consolidation, and all were in molecular remission after cycle 2. A total of 5 relapses and 3 deaths have occurred post-induction, but none of the deaths were attributable to protocol therapy. Severe adverse events were less common during the chemotherapy-free consolidation cycles, especially cycle 2. The frequency of grade 3-4 neutropenia was 62% in cycle 1 and 27% in cycle 2, but there was no grade 3-4 thrombocytopenia. The following table lists event-free survival (EFS), disease-free survival (DFS), overall survival (OS) and cumulative incidence of relapse (CIR): Table All pts LR IR HiR 2 yr 5 yr 2 yr 5 yr 2 yr 5 yr 2 yr 5 yr EFS 92% 90% 97% 97% 93% 89% 83% 83% DFS 97% 95% 100% 100% 97% 93% 95% 95% OS 94% 94% 97% 97% 96% 96% 87% 87% CIR 3% 5% 0% 0% 3% 7% 5% 5% In univariate analysis, 2+ACA predicted for inferior DFS (P = .04), whereas age 70 was associated with increased risk of early death (ED, P = .02), inferior EFS (P = .0002), and inferior OS (P = .001). Neither Sanz risk category nor FLT3 mutation status was significantly correlated with these outcome endpoints (all P .05). In multivariate analysis, the significant associations of 2+ACA (P = .04 for DFS) and age 70 (P = .0002 for EFS, P = .005 for OS) were retained. In addition, Sanz risk category was correlated with EFS (P[trend] = .003) and OS (P[trend] = .02). When compared with our previous ALLG APML3 trial (ATRA + IDA for induction and consolidation without ATO Haematologica 2012), treatment with APML4 was associated with substantial and statistically significant improvements (see Figure) in EFS (P = .002), DFS (P = .001) and OS (P = .02). The significance of trial assignment was retained in multivariate analysis when APML3 and APML4 data were combined. CONCLUSIONS APML4 is a potent anti-leukemic regimen with manageable toxicity and a low ED rate. EFS and OS remain impressive with mature follow-up, and were influenced primarily by advanced age and Sanz risk category. The CIR was 5%, and was only associated with 2+ACA. Our results support the inclusion of ATO in induction and consolidation as front-line therapy for APL whilst simultaneously limiting cumulative anthracycline exposure. Figure 1 Figure 1. Off Label Use: Arsenic trioxide is currently only registered in the US, Europe and Australia for the treatment of relapsed APL. This report includes its use in the initial treatment of APL.
Publisher: IOP Publishing
Date: 08-06-2020
DOI: 10.1088/1748-0221/15/06/P06009
Abstract: Measurements are presented of the reduction of signal output due to radiation damage for two types of plastic scintillator tiles used in the hadron endcap (HE) calorimeter of the CMS detector. The tiles were exposed to particles produced in proton-proton (pp) collisions at the CERN LHC with a center-of-mass energy of 13 TeV, corresponding to a delivered luminosity of 50 fb −1 . The measurements are based on readout channels of the HE that were instrumented with silicon photomultipliers, and are derived using data from several sources: a laser calibration system, a movable radioactive source, as well as hadrons and muons produced in pp collisions. Results from several irradiation c aigns using 60 Co sources are also discussed. The damage is presented as a function of dose rate. Within the range of these measurements, for a fixed dose the damage increases with decreasing dose rate.
Publisher: Springer Science and Business Media LLC
Date: 05-2020
Publisher: Elsevier BV
Date: 09-1992
DOI: 10.1016/0163-4453(92)94104-6
Abstract: Disseminated infection with the fungus Scedosporium inflatum in a neutropenic patient with non-Hodgkins lymphoma presented with the triad of muscle tenderness, papular skin lesions and fever, and progressed rapidly to a fatal outcome. This represents the first reported instance of fatal widely disseminated infection with this organism, and demonstrates that the triad of presenting clinical features, formerly reported to be pathognomic of systemic candidiasis, can no longer be regarded as specific for infection with a particular species of yeast or fungus.
Publisher: Springer Science and Business Media LLC
Date: 04-2020
Publisher: IOP Publishing
Date: 10-2020
Publisher: Springer Science and Business Media LLC
Date: 07-2020
Abstract: The momentum-weighted sum of the electric charges of particles inside a jet, known as jet charge, is sensitive to the electric charge of the particle initiating the parton shower. This paper presents jet charge distributions in $$ \\sqrt{s_{\\mathrm{NN}}} $$ s NN = 5 . 02 TeV lead-lead (PbPb) and proton-proton (pp) collisions recorded with the CMS detector at the LHC. These data correspond to integrated luminosities of 404 μ b − 1 and 27.4 pb − 1 for PbPb and pp collisions, respectively. Leveraging the sensitivity of the jet charge to fundamental differences in the electric charges of quarks and gluons, the jet charge distributions from simulated events are used as templates to extract the quark- and gluon-like jet fractions from data. The modification of these jet fractions is examined by comparing pp and PbPb data as a function of the overlap of the colliding Pb nuclei (centrality). This measurement tests the color charge dependence of jet energy loss due to interactions with the quark-gluon plasma. No significant modification between different centrality classes and with respect to pp results is observed in the extracted quark- and gluon-like jet fractions.
Publisher: American Society of Hematology
Date: 15-08-1994
DOI: 10.1182/BLOOD.V84.4.1220.1220
Abstract: The diagnostic and prognostic value of immunophenotyping with 18 murine monoclonal antibodies (MoAbs) to a variety of leukocyte differentiation antigens was assessed in 168 adults aged 15 to 60 years with acute myeloid leukemia (AML). Patients were entered on the multicentre Australian Leukaemia Study Group M4 protocol, and were randomized to receive either standard or high-dose Ara-C together with daunorubicin and etoposide as induction chemotherapy, followed by standard consolidation and maintenance therapy. Diagnostic bone marrow aspirate (152 cases) or peripheral blood s les (16) were analyzed by indirect immunofluorescence and flow cytometry. MoAbs used were directed at myeloid (CD11b, CD13, CD14, CD15, CD33, CD41), lymphoid (CD2, CD3, CD7, CD9, CD10, CD19), or stem cell (HLA-DR, CD34, c-kit receptor) antigens, as well as the leukocyte integrins CD18 and CD49e, and the transferrin receptor CD71. Of the myeloid markers, CD13 and CD33 were the most useful diagnostically (71% and 79% of cases positive, respectively), with CD11b, CD14, and CD15 less commonly positive. A minority of cases expressed lymphoid antigens, either T cell (CD2 16%, CD3 7%, CD7 28%) or B cell (CD10 2%, CD19 7%). CD34 was detected on 42% and c-kit receptor on 48%. When patients were analyzed for response to treatment, CD2, CD9, and CD14 were significantly associated with complete remission rate: cases expressing these antigens had a poorer response than negative cases. In univariate analysis, CD11b+ cases had shorter periods of remission (relative risk of relapse, 2.33 P = .003) and shorter survival (relative death rate, 1.91 P = .006). In multivariate analysis, adjusting for other prognostic factors, CD9 and CD11b were significantly predictive of shorter survival. No other marker had a significant predictive effect. We conclude that myeloid MoAbs are useful in confirming the diagnosis of AML, but their prognostic value may be limited to CD11b. Lymphoid antigen expression is a consistent phenomenon in a minority of cases of AML, but appears to have little clinical significance.
Publisher: Springer Science and Business Media LLC
Date: 07-2020
Abstract: The transverse energy ( $$ {E}_{\mathrm{T}}^{\upgamma} $$ E T γ ) spectra of photons isolated from other particles are measured using proton-proton (pp) and lead-lead (PbPb) collisions at the LHC at $$ \sqrt{s_{\mathrm{NN}}} $$ s NN = 5 . 02 TeV with integrated luminosities of 27.4 pb − 1 and 404 μ b − 1 for pp and PbPb data, respectively. The results are presented for photons with 25 $$ {E}_{\mathrm{T}}^{\upgamma} $$ E T γ 200 GeV in the pseudorapidity range |η| 1 . 44, and for different centrality intervals for PbPb collisions. Photon production in PbPb collisions is consistent with that in pp collisions scaled by the number of binary nucleon-nucleon collisions, demonstrating that photons do not interact with the quark-gluon plasma. Therefore, isolated photons can provide information about the initial energy of the associated parton in photon+jet measurements. The results are compared with predictions from the next-to-leading-order jetphox generator for different parton distribution functions (PDFs) and nuclear PDFs (nPDFs). The comparisons can help to constrain the nPDFs global fits.
Publisher: Wiley
Date: 06-1973
Publisher: American Society of Hematology
Date: 05-11-2021
DOI: 10.1182/BLOOD-2021-145759
Abstract: Background: WHIM (Warts, Hypogammaglobulinemia, Infections, and Myelokathexis) syndrome is a rare, autosomal-dominant primary immunodeficiency. Gain-of-function (GOF) mutations in the CXCR4 gene are the most common cause of WHIM syndrome, manifesting as panleukopenia with severe neutropenia, lymphopenia, and monocytopenia, recurrent bacterial infections, unusual susceptibility to human papillomavirus infections with intractable mucocutaneous warts, and increased risk of malignancy (McDermott DH, et al. Immunol Rev. 2019 :91-102). Mavorixafor is an investigational, small-molecule, selective antagonist of the CXCR4 receptor being developed as an oral, once-daily (QD) treatment for patients with WHIM syndrome (Dale DC, et al. Blood. 2020 (26):2994-3003). Objective: We present an update on the clinical outcomes of patients with WHIM syndrome who continued in the long-term extension of the phase 2 study, highlighting long-term safety and efficacy. Methods: A long-term extension is ongoing as part of the open-label, prospective, dose-escalation, phase 2 study evaluating the safety and efficacy of mavorixafor (NCT03005327) in adults with WHIM syndrome. In iduals with a pathogenic GOF CXCR4 mutation and absolute neutrophil count ≤400/μL and/or absolute lymphocyte count ≤650/μL were included. All provided written informed consent. The primary objectives were to evaluate safety and tolerability and assess safe dosage. Exploratory efficacy end points included changes in infection rates, number of cutaneous warts, and white blood cell counts, compared to baseline. Researchers completed detailed interviews of 4 participants continuing in the study to assess their overall study experience and perceived treatment effects. Results: Five of 8 patients in the dose-finding phase 2 study entered into the long-term extension (LTE) median treatment duration was 148.4 weeks. One patient left the LTE because of study fatigue, and all 5 patients had dose escalation to 400 mg oral QD as of May 2021. As of the November 2020 data cutoff, annualized infection rates decreased from 5.6/year at study baseline to 2.2/year at 40 months' treatment, providing evidence of persistent reduction of infections over time. At doses of 300 and 400mg QD (n=7), the mean time above threshold for ANC and ALC were 12.7 hours (SD ± 9.8) and 16.9 hours (SD ± 5.9) compared to 2.1 hours (SD ± 3.3) and 11.5 hours (SD ± 5.9) at doses ≤200 mg QD, respectively. One patient experienced a 79% reduction in warts. Safety data review at May 2021 showed that there were 12 minor treatment-emergent adverse events (grade 1) with long-term treatment (46 months), no treatment-related infections of grade 3 or higher, no treatment-related serious adverse events, and no clinically significant laboratory abnormalities with mavorixafor treatment. Patient interviews revealed that all 4 LTE participants experienced good tolerability of mavorixafor and decreased frequency, severity, and duration of infections and decreased hospital/doctor visits. Three of 4 participants reported previous need for prophylactic treatment to prevent infection of minor wounds, but with mavorixafor, minor wounds healed without infection or need for prophylaxis. The mechanism of action of mavorixafor was of interest to 3 of 4 participants, who found it important that treatment address the underlying cause of disease, not simply the symptoms. Two participants reported a QOL improvement, and the other 2 reported that WHIM syndrome never affected their QOL Conclusion: Ongoing long-term treatment of adults with WHIM syndrome with mavorixafor 300 to 400mg shows durable increase in neutrophils and lymphocytes and sustained improvements in infections and warts. Detailed patient interviews for patient global impression of changes are consistent with sustained clinical benefit of long-term treatment. Mavorixafor has the potential to be a safe, effective, and long-term therapy targeting the underlying cause of WHIM syndrome. A global phase 3 registrational study is ongoing. Dale: X4 Pharmaceuticals: Consultancy, Honoraria, Research Funding. Firkin: X4 Pharmaceuticals: Research Funding. Bolyard: X4 Pharmaceuticals: Research Funding. Tang: X4 Pharmaceuticals: Current Employment, Current equity holder in publicly-traded company. Jiang: X4 Pharmaceuticals: Current Employment, Current equity holder in publicly-traded company. MacLeod: X4 Pharmaceuticals: Current Employment, Current equity holder in publicly-traded company. Cadavid: X4 Pharmaceuticals: Current Employment, Current equity holder in publicly-traded company. Hu: X4 Pharmaceuticals: Current Employment, Current equity holder in publicly-traded company.
Publisher: Elsevier BV
Date: 12-2009
Publisher: Wiley
Date: 06-1988
DOI: 10.1111/J.1445-5994.1988.TB00124.X
Abstract: Since July 1984, eight patients with advanced hairy cell leukemia have received treatment with recombinant alpha A interferon. At commencement of interferon, seven patients had progressive cytopenia, and one was in leukemic phase (greater than 20 x 10(9)/L circulating hairy cells). All patients had had previous splenectomy. Interferon was administered subcutaneously. The initial dose was 3 x 10(6) U/day, continued until peripheral counts stabilised. Subsequently, patients received 6 x 10(6) U/day, 9 x 10(6) U/day, and finally 12 x 10(6) U/day. The dose increases proceeded every 8-12 weeks, as tolerated. Seven patients had an objective response. There were four complete remissions, two partial remissions, and one minor response. Complete remission was documented only in patients on at least 6 x 10(6) U/day for 12 weeks. The median time to complete remission was 40 weeks (range 35-53). Normalisation of peripheral blood counts preceded histologic marrow improvement. The median times for response (platelets greater than or equal to 100 x 10(9)/L, hemaglobin greater than or equal to 12 gm/dL, neutrophils greater than or equal to 1.5 x 10(9)/L), were six to eight and 17 weeks, respectively. Toxicity included myelosuppression during the first four weeks of therapy. With increasing doses of interferon, myelosuppression did not recur. A transient, mild, flu-like syndrome affected all patients. Two patients developed asymptomatic transaminitis at doses greater than 6 X 10(6) U/day. This resolved with dose reduction. In one case impotence was reported during the first four weeks of each interferon level.(ABSTRACT TRUNCATED AT 250 WORDS)
Publisher: Wiley
Date: 02-1972
DOI: 10.1111/J.1445-5994.1972.TB03903.X
Abstract: Oxygen (O2) is an essential substrate in cellular metabolism and signaling and as such is linked to the survival and normal function of metazoans. Central to the molecular mechanisms underlying O2 homeostasis are hypoxia-inducible factors (HIFs), heterodimeric transcription factors composed of O2-regulated α subunits (HIF1A/HIF-1α or EPAS1/HIF-2α), and a constitutively expressed ARNT/HIF-1β subunit, that serve as master regulators of the adaptive response to hypoxia. HIF1A and EPAS1 have both unique and overlapping functions in the regulation of erse cellular processes, but so far there has been no evidence linking HIF signaling to peroxisomes. In a recent study we identified a unique function of EPAS1 as promoter of pexophagy in hepatocytes. Here we summarize our findings and discuss potential mechanisms by which EPAS1 might trigger pexophagy.
Publisher: Elsevier BV
Date: 12-2020
Publisher: Elsevier BV
Date: 07-2020
Publisher: Springer Science and Business Media LLC
Date: 08-2020
Abstract: The combination of measurements of the W boson polarization in top quark decays performed by the ATLAS and CMS collaborations is presented. The measurements are based on proton-proton collision data produced at the LHC at a centre-of-mass energy of 8 TeV, and corresponding to an integrated luminosity of about 20 fb − 1 for each experiment. The measurements used events containing one lepton and having different jet multiplicities in the final state. The results are quoted as fractions of W bosons with longitudinal ( F 0 ), left-handed ( F L ), or right-handed ( F R ) polarizations. The resulting combined measurements of the polarization fractions are F 0 = 0 . 693 ± 0 . 014 and F L = 0 . 315 ± 0 . 011. The fraction F R is calculated from the unitarity constraint to be F R = − 0 . 008 ± 0 . 007. These results are in agreement with the standard model predictions at next-to-next-to-leading order in perturbative quantum chromodynamics and represent an improvement in precision of 25 (29)% for F 0 ( F L ) with respect to the most precise single measurement. A limit on anomalous right-handed vector ( V R ), and left- and right-handed tensor ( g L , g R ) tWb couplings is set while fixing all others to their standard model values. The allowed regions are [ − 0 . 11 , 0 . 16] for V R , [ − 0 . 08 , 0 . 05] for g L , and [ − 0 . 04 , 0 . 02] for g R , at 95% confidence level. Limits on the corresponding Wilson coefficients are also derived.
Publisher: Wiley
Date: 23-03-2015
DOI: 10.1111/EJH.12502
Abstract: To determine the potential for arsenic trioxide (ATO) to be safely and effectively incorporated into induction therapy of newly diagnosed acute promyelocytic leukaemia (APL) in patients with severe chronic renal failure (CRF) by reduction of the ATO dosage to compensate for reduced renal elimination of arsenic in CRF. Two of the four CRF patients with APL in the study were dialysis-dependent, and two had eGFRs of 18 and 19 mL/min/1.73 m(2) . ATO dosage schedules were adjusted to obtain comparable whole-blood arsenic levels to those in APL patients with normal renal function who achieved molecular remission (MR) while receiving 10 mg ATO daily for 28 d. Average ATO administered per day in CRF patients ranged from 36 to 50% of the ATO administered to APL patients with normal renal function. No clinically significant cardiac, hepatic or other toxicities were detected. RT-PCR-negative MR was achieved after one treatment course in two patients and after two courses in the others. Relapse-free survival is 155, 60, 43 and 5 months. The observations in this pilot study have demonstrated whole-blood arsenic levels can provide a guide to adjustments of ATO dosage schedules that permit safe and effective therapeutic outcomes in APL patients with severely compromised renal function.
Publisher: Informa UK Limited
Date: 1993
DOI: 10.3109/08977199309046933
Abstract: The response of hemopoietic activity in long term culture of human bone marrow (LTMC) to exogenous c-kit ligand has been investigated. Addition of c-kit ligand as recombinant Stem Cell Factor after the adherent stromal cell layer had become confluent failed to increase the content of hemopoietic cells in the culture system. Production of hemopoietic progenitors and differentiated progeny was on the other hand lified by addition of c-kit ligand at regular intervals from the initiation of the culture, and resulted in net formation of these cells in the culture system. The characteristics of the response were consistent with consequences of increased survival of hemopoietic progenitors during a vulnerable initial phase in which the availability of endogenous c-kit ligand was limited by the initially low number of stromal cells. The increase in differentiated progeny was essentially due to increased formation of neutrophil series, and the lack of increased basophil production under these circumstances presumably reflected the nature of the contributory effects of endogenously generated growth regulatory molecules which acted in a synergistic manner with added c-kit ligand.
Publisher: Elsevier BV
Date: 02-1984
DOI: 10.1016/0022-1759(84)90344-2
Abstract: The pattern of absorption of the different major immunoglobulin classes by protein A and protein A coupled with antibody to human IgA or IgM has been evaluated as a simple means of identifying the class of a particular immunoglobulin in small volumes of human serum. Rabbit anti-IgA or anti-IgM coupled with protein A-Sepharose gel effectively removed IgA or IgM respectively from human serum in addition to the subclasses of IgG removed by protein A alone. The manner in which an immunoglobulin-related property is removed from human serum by protein A and its conjugates with specific antibodies can thus serve as an index of the class of that particular immunoglobulin.
Publisher: American Physical Society (APS)
Date: 21-05-2020
Publisher: Springer Science and Business Media LLC
Date: 11-2020
Abstract: The ratios of the production cross sections between the excited ϒ(2S) and ϒ(3S) mesons and the ϒ(1S) ground state, detected via their decay into two muons, are studied as a function of the number of charged particles in the event. The data are from proton-proton collisions at $$ \\sqrt{s} $$ s = 7 TeV, corresponding to an integrated luminosity of 4.8 fb − 1 , collected with the CMS detector at the LHC. Evidence of a decrease in these ratios as a function of the particle multiplicity is observed, more pronounced at low transverse momentum $$ {p}_{\\mathrm{T}}^{\\upmu \\upmu} $$ p T μμ . For ϒ(nS) mesons with $$ {p}_{\\mathrm{T}}^{\\upmu \\upmu} $$ p T μμ 7 GeV, where most of the data were collected, the correlation with multiplicity is studied as a function of the underlying event transverse sphericity and the number of particles in a cone around the ϒ(nS) direction. The ratios are found to be multiplicity independent for jet-like events. The mean $$ {p}_{\\mathrm{T}}^{\\upmu \\upmu} $$ p T μμ values for the ϒ(nS) states as a function of particle multiplicity are also measured and found to grow more steeply as their mass increases.
Publisher: Wiley
Date: 06-1982
DOI: 10.1111/J.1445-5994.1982.TB02468.X
Abstract: Discriminant and regression analyses were employed to determine the influence of a large number of clinical and laboratory indices on outcome of treatment in a series of 158 adults presenting with acute leukaemia between 1970 and 1977. Induction therapy had been most commonly cytosine arabinoside plus daunorubicin, vincristine and prednisolone. This induced complete remission in 42% of non-lymphoblastic, and in 58% of lymphoblastic plus undifferentiated leukaemias. Some induction failures who had non-lymphoblastic leukaemia were treated with cytosine arabinoside plus 6-thioguanine, which induced remissions in 46%. Advanced age was the factor most strongly associated with failure either to achieve or to sustain complete remission. Thrombocytopenia, promyelocytic leukaemia, high percentage of marrow blasts, and absence of metaphases in marrow cytogenetic preparations were also associated with poor survival. A number of other factors which appeared to be associated with poor prognosis were found by the analysis to lack significance as independent variables.
Publisher: AMPCo
Date: 08-1977
DOI: 10.5694/J.1326-5377.1977.TB117649.X
Abstract: A case of agranulocytosis due to dapsone administered for the treatment of acne vulgaris is described. Agranulocytosis has previously been reported after administration of dapsone for other dermatological disorders, leprosy, and prophylaxis against falciparum malaria. The frequency of agranulocytoses when dapsone was used for malaria prophylaxis in United States servicemen in Vietnam was sufficient to result in its withdrawal from use for this purpose. Caution should therefore be exercised in the administration of dapsone for conditions for which less toxic agents are available.
Publisher: Springer Science and Business Media LLC
Date: 07-2020
Abstract: A search for charged Higgs bosons (H ± ) decaying into a top and a bottom quark in the all-jet final state is presented. The analysis uses LHC proton-proton collision data recorded with the CMS detector in 2016 at $$ \\sqrt{s} $$ s = 13 TeV, corresponding to an integrated luminosity of 35.9 fb − 1 . No significant excess is observed above the expected background. Model-independent upper limits at 95% confidence level are set on the product of the H ± production cross section and branching fraction in two scenarios. For production in association with a top quark, limits of 21.3 to 0.007 pb are obtained for H ± masses in the range of 0.2 to 3 TeV. Combining this with a search in leptonic final states results in improved limits of 9.25 to 0.005 pb. The complementary s -channel production of an H ± is investigated in the mass range of 0.8 to 3 TeV and the corresponding upper limits are 4.5 to 0.023 pb. These results are interpreted using different minimal supersymmetric extensions of the standard model.
Publisher: Elsevier BV
Date: 1991
DOI: 10.3109/00313029109063567
Abstract: The effectiveness of immunoperoxidase staining for platelet glycoprotein IIb/IIIa coupled with cytochemical staining for hemoglobin has been evaluated as a dual staining technique for identifying lineage-specific characteristics of the megakaryocytic and erythroid series in cells of the same hemopoietic tissue preparation. A sequence of staining was established which produced a circumferential brown stain around cells of the megakaryocytic series, and a diffuse yellow to orange stain in the cytoplasm of cells of the erythroid series. Each staining reaction possessed a high degree of specificity and sensitivity which enabled the combined stain to provide a convenient means for establishing the megakaryocytic and erythroid nature of in idual cells in hematological specimens where classification cannot be achieved with certainty on morphological grounds.
Publisher: Wiley
Date: 05-1968
DOI: 10.1111/IMJ.1968.17.2.127
Abstract: This study is a secondary analysis of outcomes examining risk behavior in the context of the naturalistic occurrence of parental monitoring and participation in an emotion regulation intervention over a 12-month period. Early adolescents with mental health symptoms (N=420), ages 12-14 years, were recruited and randomized into either an Emotional Regulation (ER) or Health Promotion (HP) condition. Assessments included adolescent self-report of unsupervised time, substance use and sexual behavior at baseline, 6-months, and one year post-intervention. Analytic groups were formed by intervention condition (ER or HP) and baseline reports of unsupervised time (≤1× per week or >1× per week of unsupervised time with opposite sex peers) resulting in a total of four groups. Logistic regression and time-to-event analyses were used to test differences in substance use and delay of sexual initiation between the groups. Participation in the ER intervention in the presence of low unsupervised time was superior in reducing both substance use and sexual initiation than either factor alone and either factor alone was more effective than the absence of both. Findings suggest that interventions targeting health risk behaviors, including substance use and sexual risk behavior, among early adolescents with mental health symptoms may be more effective when targeting both internal (e.g., emotional regulation) and external (e.g., unsupervised time spent with peers) protective factors. Limiting unsupervised time spent with peers through parental monitoring may serve to scaffold and reinforce early adolescent acquisition of effective emotion regulation which can be employed during emotionally arousing risk situations.
Publisher: Wiley
Date: 05-1993
DOI: 10.1111/J.1365-2141.1993.TB03019.X
Abstract: The capacity of diffusible molecules in the fluid phase of long-term human bone marrow culture (LTMC) to exert preferential adverse effects on leukaemic relative to normal haemopoietic cells has been investigated. Responses of isolated cell populations were assessed in diffusion chamber inserts which permitted contact with fluid phase molecules but not with the adherent stromal cell layer of the LTMC system. Growth of AML cells in diffusion chambers was inhibited during co-culture with LTMC of autologous leukaemic bone marrow, and the same effect was produced during co-culture with normal LTMC. No inhibitory action was exerted on growth of normal haemopoietic precursors under the same conditions. Comparable responses were observed with human leukaemic cell lines and patient leukaemic cells, and studies on cell lines demonstrated inhibition of growth was induced by molecules generated in LTMC which caused accumulation in G1 phase of leukaemic cells of both myeloid and lymphoid lineage. The inhibitory effect was not reproduced by TGF beta, IFN gamma, IFN alpha, TNF alpha, LIF, SCF or Il-6, and was not impaired by inhibitors of nitric oxide or PGE production in the LTMC. These observations suggest the action of diffusible molecules of undefined constitution contributes to the preferential loss of leukaemic cells in LTMC.
Publisher: Wiley
Date: 08-1988
DOI: 10.1111/J.1445-5994.1988.TB00158.X
Abstract: In this review we have discussed the data which indicates that differentiation can indeed occur to a limited degree in the neoplastic cells in acute leukemia and myelodysplastic syndromes. Attempts to increase the degree of differentiation as an approach to the treatment of these disorders have utilised a variety of chemical agents which have been reported to exert such an effect in vitro. Analysis of the results, however, indicates that beneficial effects of these agents in patients is due to cytotoxic action which selectively reduces the neoplastic cell population. Leukemic cells can also undergo incomplete differentiation in vitro when exposed to appropriate growth factors, which raises the question of whether leukemia and myelodysplasia can be treated by the induction of differentiation in the malignant cells following the administration of these agents. This question, and questions about the nature of complete remission, will be answered in the coming years by clinical trials of growth factors, and further studies of the DNA in mature cells to analyse whether these cells are derived from leukemic progenitors.
Publisher: Wiley
Date: 02-2019
DOI: 10.1111/IMJ.14140
Abstract: Acquired aplastic anaemia is a rare, serious, immunologically mediated bone marrow failure syndrome, characterised by marrow hypoplasia of varying severity and significant pancytopenia. Careful attention and investigation, including molecular testing, is required to confirm the diagnosis and exclude other mimicking conditions, such as inherited bone marrow failure syndromes. In a proportion of patients, the disease evolves to myelodysplasia or acute myeloid leukaemia and in some there is an association with paroxysmal nocturnal haemoglobinuria. The disease has a major impact on patient quality of life. Haemopoietic stem rogenitor cell transplantation for eligible patients with an available donor is the only current curative therapy. Other patients may receive immunosuppression, most commonly with anti-thymocyte globulin and cyclosporin. An initial response to immunosuppression is often encouraging, but relapse is common. Supportive care, including management of transfusion requirements and infections, is central to management. Promising new diagnostic tools and emerging therapies will likely transform approaches to this important, chronic and life-threatening condition.
Publisher: Wiley
Date: 10-1983
DOI: 10.1111/J.1600-0609.1983.TB00663.X
Abstract: The influence of human serum components during in vitro determination of erythropoietin biological activity has been examined in a modified in vitro bioassay procedure utilising rabbit bone marrow as the erythropoietin-responsive tissue. The number of erythroblasts present after 5 d in suspension culture provided a measure of erythropoietin biological activity with a degree of sensitivity equivalent to that provided by estimation of 59Fe incorporation into haem, but possessed the advantage of lacking the susceptibility of the latter method to the level of human serum transferrin saturation. Erythropoietic stimulation was blocked by 10% human serum unless all sera incorporated into the bioassay was previously heated at 56 degrees C. Human serum under the latter conditions was shown to contain material which stimulated erythropoiesis, but which differed in its mode of action from erythropoietin in that it operated by lifying the response to erythropoietin. Correction for these effects substantially altered interpretation of erythropoietic stimulatory activity of human serum to yield values in keeping with those reported for in vivo bioassay. These findings illustrate the need to clarify the role of human serum components which modify the action of erythropoietin under culture conditions, in view of their potential contribution to discrepancies between values obtained by different bioassay procedures.
Publisher: Springer Science and Business Media LLC
Date: 10-08-2022
DOI: 10.1007/S10875-022-01312-7
Abstract: Warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndrome (WS) is a combined immunodeficiency caused by gain-of-function mutations in the C-X-C chemokine receptor type 4 ( CXCR4 ) gene. We characterize a unique international cohort of 66 patients, including 57 (86%) cases previously unreported, with variable clinical phenotypes. Of 17 distinct CXCR4 genetic variants within our cohort, 11 were novel pathogenic variants affecting 15 in iduals (23%). All variants affect the same CXCR4 region and impair CXCR4 internalization resulting in hyperactive signaling. The median age of diagnosis in our cohort (5.5 years) indicates WHIM syndrome can commonly present in childhood, although some patients are not diagnosed until adulthood. The prevalence and mean age of recognition and/or onset of clinical manifestations within our cohort were infections 88%/1.6 years, neutropenia 98%/3.8 years, lymphopenia 88%/5.0 years, and warts 40%/12.1 years. However, we report greater prevalence and variety of autoimmune complications of WHIM syndrome (21.2%) than reported previously. Patients with versus without family history of WHIM syndrome were diagnosed earlier (22%, average age 1.3 years versus 78%, average age 5 years, respectively). Patients with a family history of WHIM syndrome also received earlier treatment, experienced less hospitalization, and had less end-organ damage. This observation reinforces previous reports that early treatment for WHIM syndrome improves outcomes. Only one patient died death was attributed to complications of hematopoietic stem cell transplantation. The variable expressivity of WHIM syndrome in pediatric patients delays their diagnosis and therapy. Early-onset bacterial infections with severe neutropenia and/or lymphopenia should prompt genetic testing for WHIM syndrome, even in the absence of warts.
Publisher: Therapeutic Guidelines Limited
Date: 08-2009
Publisher: Wiley
Date: 08-1987
DOI: 10.1111/J.1445-5994.1987.TB00069.X
Abstract: The place of cytosine arabinoside (araC) in the treatment of T-cell acute lymphoblastic leukemia was studied by measuring nucleoside transport sites and the conversion of araC to its triphosphate (araCTP) in lymphoblasts from the peripheral blood of two patients, who were then treated with araC. Equilibrium binding of 3H-nitrobenzylmercaptopurine riboside (3H-NBMPR), a specific ligand of the nucleoside transporter, gave 16,510 to 29,400 sites/cell for T-lymphoblasts on presentation or early in relapse compared with 2730 +/- 1570 sites/cell for non-T-lymphoblasts. Accumulation of araCTP from 1 microM araC was four times greater in T-cell than non-T-cell lymphoblasts. One patient was treated with araC (100 mg/m2 daily x 7 days, continuous intravenously) at the time of her first leukemic relapse and complete remission was achieved with this single agent. When this patient relapsed and developed advanced disease the T lymphoblasts showed a 75% reduction in their ability to accumulate araCTP which paralleled a reduction in 3H-NBMPR binding. The second patient achieved complete remission with araC given in low dose (15 mg twice daily by subcutaneous injection) for 21 days at the time of a localised relapse in the mediastinum and pleura. These studies suggest that araC may have a place in the therapy of early stage T-lymphoblastic disease.
Publisher: American Physical Society (APS)
Date: 24-11-2020
Publisher: American Society for Clinical Investigation
Date: 08-1972
DOI: 10.1172/JCI107015
Publisher: Springer Science and Business Media LLC
Date: 09-2020
Abstract: A search for new physics in events with two highly Lorentz-boosted Z bosons and large missing transverse momentum is presented. The analyzed proton-proton collision data, corresponding to an integrated luminosity of 137 fb − 1 , were recorded at $$ \\sqrt{s} $$ s = 13 TeV by the CMS experiment at the CERN LHC. The search utilizes the substructure of jets with large radius to identify quark pairs from Z boson decays. Backgrounds from standard model processes are suppressed by requirements on the jet mass and the missing transverse momentum. No significant excess in the event yield is observed beyond the number of background events expected from the standard model. For a simplified supersymmetric model in which the Z bosons arise from the decay of gluinos, an exclusion limit of 1920 GeV on the gluino mass is set at 95% confidence level. This is the first search for beyond-standard-model production of pairs of boosted Z bosons plus large missing transverse momentum.
Publisher: American Physical Society (APS)
Date: 05-10-2020
Publisher: Elsevier BV
Date: 10-1978
DOI: 10.1016/S0140-6736(78)91570-2
Abstract: In a prospective, controlled trial 26 anaemic, neutropenic children with newly diagnosed acute lymphocytic leukaemia were randomised in pairs to receive either transfusion to a haemoglobin of 10--12 g/dl where clinically indicated (group A) or hypertransfusion to a haemoglobin of 16--18 g/dl (group B). Compared with group A (11 of 13 transfused), group B (all transfused) had a significantly more rapid rise in neutrophils at 7 and 10 days post-transfusion, a lower incidence of infection, and less interruption to chemotherapy. Hypertransfusion restored the myeloid/erythroid ratio to normal in bone-marrow of 5 of 6 children and the proportion of early myeloid precursors was greater than in controls.
No related grants have been discovered for Frank Firkin.