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341.
The common 'thermolabile' variant of methylene tetrahydrofolate reductase is a major determinant of mild hyperhomocysteinaemia 总被引:11,自引:0,他引:11
Harmon DL; Woodside JV; Yarnell JW; McMaster D; Young IS; McCrum EE; Gey KF; Whitehead AS; Evans AE 《QJM : monthly journal of the Association of Physicians》1996,89(8):571-577
Mild hyperhomocysteinaemia is a major risk factor for vascular disease and
neural tube defects (NTDs), conferring an approximately three-fold relative
risk for each condition. It has several possible causes: heterozygosity for
rare loss of function mutations in the genes for 5,10-methylene
tetrahydrofolate reductase (MTHFR) or cystathionine-&bgr;-synthase
(CBS); dietary insufficiency of vitamin co-factors B6, B12 or folates; or
homozygosity for a common 'thermolabile' mutation in the MTHFR gene which
has also been associated with vascular disease and NTDs. We quantified the
contribution of the thermolabile mutation to the hyperhomocysteinaemic
phenotype in a working male population (625 individuals). Serum folate and
vitamin B12 concentrations were also measured and their relationship with
homocysteine status and MTHFR genotype assessed. The homozygous
thermolabile genotype occurred in 48.4, 35.5, and 23.4% for the top 5, 10
and 20% of individuals repectively) ranked by plasma homocysteine levels,
compared with a frequency of 11.5% in the study population as a whole
establishing that the mutation is a major determinant of homocystein levels
at the upper end of the range. Serum folate concentrations also varied with
genotype, being lowest in thermolabile homozygotes. The MTHFR thermolabile
genotype should be considered when population studies are designed to
determine the effective homocysteine-lowering dose of dietary folate
supplements, and when prophylactic doses of folate are recommended for
individuals.
相似文献
342.
Mannose-binding lectin status is associated with risk of major infection following myeloablative sibling allogeneic hematopoietic stem cell transplantation
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Mullighan CG Heatley SL Danner S Dean MM Doherty K Hahn U Bradstock KF Minchinton R Schwarer AP Szer J Bardy PG 《Blood》2008,112(5):2120-2128
Mannose-binding lectin (MBL) is a mediator of innate immunity that influences the risk of infection in a range of clinical settings. We previously reported associations between MBL2 genotype and infection in a retrospective study of myeloablative allogeneic hematopoietic stem cell transplantation (allo-HCT). However, other studies have been inconclusive, and the role of MBL in reduced-intensity conditioning (RIC) transplantation is unknown. Here we report a prospective study examining MBL2 genotype, MBL levels, and risk of major infection following HLA-matched sibling myeloablative (n = 83) and RIC (n = 59) HCT. Baseline MBL levels were higher in recipients than donors (P < .001), and recipient MBL levels increased during the peritransplantation period (P = .001), most notably in MBL2 wild-type individuals receiving myeloablative total body irradiation (mTBI). MBL2 coding mutations were associated with major infection in recipients receiving mTBI. The cumulative incidence of major infection in recipient harboring an MBL2 mutation receiving mTBI was 70.6%, compared with 31.1% of those without mutations not receiving mTBI (P = .01). MBL status was not associated with infection in RIC transplants. These results confirm the association of MBL status with risk of infection in myeloablative, TBI-conditioned transplantation. Studies examining the role of MBL replacement therapy to prevent infection in this setting should be considered. 相似文献
343.
Wirth A Prince HM Wolf M Stone JM Matthews J Gibson J Macleod C Szer J Grigg A To B Roos D Schwarer AP Davis S;Australasian Leukaemia Lymphoma Group 《Bone marrow transplantation》2005,35(3):291-298
This study evaluated delivery of involved field radiotherapy (IFRT) with transplantation for lymphomas timed to minimise toxicity. Patients transplanted for lymphoma had infradiaphragmatic disease irradiated pre-transplant and supradiaphragmatic disease post transplant. A total of 31 patients were studied, with a median follow-up duration of 4 years. Transplant conditioning was according to clinician preference. In all, 14 patients had pre-transplant abdominopelvic IFRT and 19 had post transplant IFRT (including three who had pre-transplant IFRT). Grade III-IV haematological toxicity from pre-transplant IFRT occurred in three patients and from post transplant IFRT in 10 patients. Pre-transplant IFRT had no effect on haematological recovery post transplant, but was associated with a trend towards increased gastrointestinal toxicity (P = 0.094). Pneumonitis due to post transplant thoracic IFRT occurred in one patient. Two patients failed in involved sites after completion of protocol radiotherapy. One case of myelodysplasia has been reported. As sequenced in this study, IFRT was feasible and produced a low incidence of severe pulmonary and haematological toxicities. Patient selection, field size and radiotherapy dose warrant further study. 相似文献
344.
Ashlea Campbell Benjamin Teh Stephen Mulligan David M. Ross Robert Weinkove Nicole Gilroy Shane Gangatharan Henry Miles Prince Jeff Szer Judith Trotman Steven Lane Michael Dickinson Hang Quach Anoop K. Enjeti Matthew Ku Gareth Gregory Gregory Hapgood Phoebe Joy Ho Tara Cochrane Chan Cheah Matthew Greenwood Maya Latimer Leanne Berkahn Joel Wight Tasman Armytage Peter Diamond Constantine S. Tam Nada Hamad 《Internal medicine journal》2024,54(2):328-336
Despite widespread vaccination rates, we are living with high transmission rates of SARS-CoV-2. Although overall hospitalisation rates are falling, the risk of serious infection remains high for patients who are immunocompromised because of haematological malignancies. In light of the ongoing pandemic and the development of multiple agents for treatment, representatives from the Haematology Society of Australia and New Zealand and infectious diseases specialists have collaborated on this consensus position statement regarding COVID-19 management in patients with haematological disorders. It is our recommendation that both patients with haematological malignancies and treating specialists be educated regarding the preventive and treatment options available and that patients continue to receive adequate vaccinations, keeping in mind the suboptimal vaccine responses that occur in haematology patients, in particular, those with B-cell malignancies and on B-cell-targeting or depleting therapy. Patients with haematological malignancies should receive treatment for COVID-19 in accordance with the severity of their symptoms, but even mild infections should prompt early treatment with antiviral agents. The issue of de-isolation following COVID-19 infection and optimal time to treatment for haematological malignancies is discussed but remains an area with evolving data. This position statement is to be used in conjunction with advice from infectious disease, respiratory and intensive care specialists, and current guidelines from the National COVID-19 Clinical Evidence Taskforce and the New Zealand Ministry of Health and Cancer Agency Te Aho o Te Kahu COVID-19 Guidelines. 相似文献
345.
346.
John Moore Peter Brooks Sam Milliken Jim Biggs David Ma Malcolm Handel Paul Cannell Rob Will Simon Rule David Joske Bob Langlands Kerry Taylor Joe O'Callaghan Jeff Szer Ian Wicks Geoff McColl Frances Passeullo John Snowden 《Arthritis \u0026amp; Rheumatology》2002,46(9):2301-2309
Objective
Evidence from animal studies, case reports, and phase I studies suggests that hemopoietic stem cell transplantation (HSCT) can be effective in the treatment of rheumatoid arthritis (RA). It is unclear, however, if depletion of T cells in the stem cell product infused after high‐dose chemotherapy is beneficial in prolonging responses by reducing the number of infused autoreactive T cells. This pilot multicenter, randomized trial was undertaken to obtain feasibility data on whether CD34 selection (as a form of T cell depletion) of an autologous stem cell graft is of benefit in the HSCT procedure in patients with severe, refractory RA.Methods
Thirty‐three patients with severe RA who had been treated unsuccessfully with methotrexate and at least 1 other disease‐modifying agent were enrolled in the trial. The patients received high‐dose immunosuppressive treatment with 200 mg/kg cyclophosphamide followed by an infusion of autologous stem cells that were CD34 selected or unmanipulated. Safety, efficacy (based on American College of Rheumatology [ACR] response criteria), and time to recurrence of disease were assessed on a monthly basis for up to 12 months.Results
All patients were living at the end of the study, with no major unexpected toxicities. Overall, on an intent‐to‐treat basis, ACR 20% response (ACR20) was achieved in 70% of the patients. An ACR70 response was attained in 27.7% of the 18 patients who had received CD34‐selected cells and 53.3% of the 15 who had received unmanipulated cells (P = 0.20). The median time to disease recurrence was 147 days in the CD34‐selected cell group and 201 days in the unmanipulated cell group (P = 0.28). There was no relationship between CD4 lymphopenia and response, but 72% of rheumatoid factor (RF)–positive patients had an increase in RF titer prior to recurrence of disease.Conclusion
HSCT can be performed safely in patients with RA, and initial results indicate significant responses in patients with severe, treatment‐resistant disease. Similar outcomes were observed in patients undergoing HSCT with unmanipulated cells and those receiving CD34‐selected cells. Larger studies are needed to confirm these findings.347.
348.
Shirlene Sim Anna Kalff Gina Tuch Peter Mollee P. Joy Ho Simon Harrison Simon Gibbs H. Miles Prince Andrew Spencer Douglas Joshua Cindy Lee Silvia Ling Nick Murphy Ferenc Szabo Jeff Szer Nicholas Weber Christopher Ward Dipti Talaulikar Andrew Zannettino Hang Quach 《Internal medicine journal》2023,53(5):819-824
Multiple myeloma (MM) is a disease of older people, yet factors relating to comorbidity and frailty may threaten treatment tolerability for many of this heterogenous group. There has been increasing interest in defining specific and clinically relevant frailty assessment tools within the MM population, with the goal of using these frailty scores, not just as a prognostic instrument, but also as a predictive tool to allow for a frailty-adapted treatment approach. This paper reviews the various frailty assessment frameworks used in the evaluation of patients with MM, including the International Myeloma Working Group Frailty Index (IMWG-FI), the Mayo Frailty Index and the simplified frailty scale. While the IMWG-FI remains the most widely accepted tool, the simplified frailty scale is the most user-friendly in busy day-to-day clinics based on its ease of use. This paper summarises the recommendations from the Myeloma Scientific Advisory Group (MSAG) of Myeloma Australia, on the use of frailty assessment tools in clinical practice and proposes a frailty-stratified treatment algorithm to aid clinicians in tailoring therapy for this highly heterogeneous patient population. 相似文献
349.
Lauren M. Pachman MD Jennifer R. Hayford RN Marc C. Hochberg Md Mph Mark A. Pallansch PhD Ahn Chung BS Claire D. Daugherty MS Balu H. Athreya MD Suzanne L. Bowyer MD Chester W. Fink MD Harry L. Gewanter MD Rita Jerath MD Bianca A. Lang MD Ilona S. Szer MD James Sinacore PhD Mary L. Christensen PhD Alan R. Dyer PhD 《Arthritis \u0026amp; Rheumatology》1997,40(8):1526-1533
Objective. To determine, in a case-control study, if patients with new-onset juvenile dermatomyositis (juvenile DM) have increased symptoms prior to onset, exposure to certain environmental conditions, frequency of familial autoimmune diseases, or antibody titers, compared with 2 control groups. Methods. A structured interview with the families of 80 children with juvenile DM, 40 children with juvenile rheumatoid arthritis (JRA), or 23 healthy children, from the same geographic area as the children with juvenile DM, was conducted. All children's sera were tested for antibody to Toxoplasma gondii, herpes simplex virus (HSV), or coxsackievirus B (CVB). Results. A high proportion of children with juvenile DM had constitutional symptoms 3 months before the disease-onset date (P = 0.013 versus control children). Children with JRA had more relatives with rheumatoid arthritis (P = 0.0001) and pernicious anemia (P = 0.003) than did children with juvenile DM or healthy children. Among children ⩽7 years of age, elevated enteroviral titers were more frequent in those with juvenile DM (81%) and in healthy controls (90%) than in those with JRA (64%), suggesting a common environmental exposure. Titers to T gondii, HSV, or CVB 1-6 were normal. Conclusion. Frequencies of familial autoimmune disease, exposure to environmental factors, or elevated antibody titers to T gondii, HSV, or CVB are not increased in juvenile DM. Children with juvenile DM do have symptoms of illness 3 months before the disease-onset date, and young patients have elevated enteroviral titers, as do young geographic controls. 相似文献