To redevelop a neutralizing antibody (NAb) assay to be much more drug tolerant, have a large dynamic range and have high inhibition when using high levels of positive control (PC). Early assay data suggested that typical biotin labeling of the capture reagent (Drug 1, produced in a human cell line) was blocking it from binding with the PC or the detection target, and that the detection target was out competing the PC. Methodical biotin labeling experiments were performed at several challenge ratios and an Fc linker was added to the detection target.
View Article and Find Full Text PDFThe measurement of antidrug antibodies (ADA) in nonclinical studies provides limited value because the formation and incidence of nonclinical ADA does not translate to clinical experience. The formation and presence of ADA in nonclinical species can, however, correlate to reduced drug exposure and safety observations including vasculitis and immune complex disease. Generic ADA methods for humanized monoclonal antibody biotherapeutics mitigate the need to develop bespoke ADA methods during nonclinical drug development.
View Article and Find Full Text PDFInconsistent or careless responding is a significant threat to the validity of self-reported personality data. Using archival samples of undergraduate and community participants, we developed an inconsistent responding scale using items that appear on both the 60- and 100-item versions of the HEXACO Personality Inventory-Revised-two widely used measures of the HEXACO model of personality trait structure. We identified pairs of correlated HEXACO items in Sample 1 and created a total inconsistent responding score by summing absolute differences between each item pair.
View Article and Find Full Text PDFObjective: To determine the long-term outcome of Maori and Pacific Island children diagnosed with childhood onset lupus nephritis.
Method: A chart review was conducted of children diagnosed with biopsy proven lupus nephritis seen by the Starship Hospital and Kidz First paediatric rheumatology and/or Starship renal services between January 1992 and January 2018. Baseline and follow-up kidney histology, adherence and response to therapy including partial or full renal remission, refractory disease, end-stage kidney disease (ESKD) and mortality were determined.
Aim: To describe the incidence, demographics, diagnostic clinical manifestations and long-term outcomes of juvenile dermatomyositis (JDM) in Maori and Pacific Island compared to European children.
Methods: A chart review was conducted of children with JDM seen by the Starship Rheumatology service between 2000 and 2020. Diagnostic clinical manifestations, demographics, disease course and significant complications were collated.
Hydroxychloroquine (HCQ) suppresses an interleukin-1β-granulocyte-macrophage colony-stimulating factor cytokine axis, reported to be dysregulated in peripheral blood mononuclear cells of acute rheumatic fever patients ex vivo. We describe HCQ treatment for 2 patients with rheumatic carditis and a protracted inflammatory course. HCQ was associated with control of inflammatory markers, control of pericarditis in first patient and stabilization of progressive carditis in the second patient.
View Article and Find Full Text PDFPrison mental health services have tended to focus on improving the quality of care provided to mentally disordered offenders at the initial point of contact with the prison system and within the prison environment itself. When these individuals reach the end of their sentence and return to the community, there is an increased risk of morbidity, mortality, homelessness and re-imprisonment. New models of care have been developed to minimize these risks.
View Article and Find Full Text PDFArthritis Care Res (Hoboken)
September 2019
Objective: To describe the incidence, demographics, diagnostic clinical manifestations, and severity of juvenile idiopathic arthritis (JIA) in Maori and Pacific Island children compared to European children.
Methods: A chart review was conducted of all children with JIA seen by Auckland pediatric and rheumatology services between the years 2000 and 2015. Demographic data and diagnostic clinical manifestations, including poor prognostic features, were collated.
Introduction: Patient immobilisation is critically important for both highly conformal conventionally fractionated radiotherapy and for stereotactic body radiotherapy. Different immobilisation devices are available to maintain patient position for radiotherapy but the most suitable one remains unknown.
Methods: Forty-five patients were randomly allocated to one of three immobilisation devices; the Q fix arm shuttle, BodyFIX without wrap or BodyFIX with wrap.
Objectives: To describe the incidence, diagnostic clinical manifestations and severity of juvenile systemic lupus erythematosus (jSLE) in a cohort of New Zealand Maori and Pacific Island children compared to European children.
Methods: A chart review was conducted of children with jSLE seen by the Starship paediatric rheumatology and/or renal services between January 2000 and November 2010. Diagnostic clinical data and lupus nephritis data at anytime were collated while classic British Isles Lupus Assessment Group (BILAG) and Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) scores were derived retrospectively.
We present two cases of bone marrow necrosis not associated with malignancy, infection or sickle cell disease. The first case, a 28 year old woman with the antiphospholipid syndrome and a factor V Leiden abnormality, suffered an illness characterised by multiple organ thromboses, anemia and refractory thrombocytopenia. She had documented bone marrow necrosis of the posterior iliac spine and numerous hot spots on bone scanning suggestive of widespread marrow necrosis.
View Article and Find Full Text PDFA comparison was made of the pattern of interstitial pneumonitis (IP) following allogeneic bone marrow transplantation before and after the introduction of ganciclovir prophylaxis to minimize the risk of cytomegalovirus (CMV) disease in the St Vincent's Hospital bone marrow transplant program in 1989. A total of 456 recipients of allogeneic transplants were included. 280 received no prophylactic ganciclovir while 176 received prophylactic ganciclovir.
View Article and Find Full Text PDFBackground: HLA-identical sibling bone marrow transplantation is an accepted treatment for patients with acute myeloid leukaemia (AML) and chronic myeloid leukaemia (CML). We have recently reported improving results in HLA-identical sibling transplant over the ten year period 1981-1990. In this report we described the outcome in patients transplanted at St Vincent's Hospital, Sydney between 1989 and 1993.
View Article and Find Full Text PDFBackground: Lengthy remission or cure has remained elusive for patients with many of the common haematological malignancies. Thus high dose chemotherapy followed by autologous haemopoietic stem cell transplantation is being increasingly utilised in these diseases.
Aim: To assess the safety of high dose chemotherapy and autologous stem cell transplantation in haematological malignancy.
Ninety one patients between the ages of 17 and 58 years undergoing histocompatible allogeneic transplants from sibling donors were entered into a double-blind randomised trial to evaluate the effect of human erythropoietin (rhu EPO) at a dose of 300 units per kg/day given thrice weekly by intravenous injection on erythropoiesis and on erythrocyte and platelet transfusion requirements. Dose was ceased when the haemoglobin exceeded 12g/dL and recommenced if the haemoglobin fell below 12 g/dL, at 150 units/kg/day. If the haemoglobin exceeded 12 g/dL on a further occasion, the dose of rhu EPO was not given.
View Article and Find Full Text PDFBackground: Only 30% of patients with leukaemia have an HLA-compatible family member able to act as a marrow donor. The recent development of volunteer bone marrow donor registries has supplied HLA-matched donors for a number of such individuals.
Aims: To define the problem and outcome of the first cohort of patients given HLA-matched unrelated volunteer bone marrow transplants at St Vincent's Hospital, Sydney.
Allogeneic bone marrow transplantation (BMT) has been shown to result in long-term disease-free survival in patients with leukemia. However, the utility of this treatment approach is limited by treatment-related morbidity and mortality. We present an update of a study in which a BMT preparative regimen consisting of a 4-day course of busulfan and a 2-day course of cyclophosphamide (BuCy2) was used in patients with chronic myelogenous leukemia.
View Article and Find Full Text PDFDuring the years 1981-90 inclusive 227 patients with haematological malignancy received an HLA-identical sibling first transplant at St Vincent's Hospital, Sydney. Recipients with acute leukaemia in first remission or chronic myeloid leukaemia in first chronic phase were analysed as good risk, and those beyond these stages, as poor risk patients. Good risk patients transplanted in the years 1986-90 (n = 52) showed improved actuarial survival (74%) compared to those (n = 58) transplanted during 1981-85 (37%, p = 0.
View Article and Find Full Text PDFOne hundred fifteen patients with chronic myelocytic leukemia (CML) were administered busulphan 4 mg/kg for 4 days and cyclophosphamide 60 mg/kg on each of 2 days (BuCy2) followed by allogeneic bone marrow transplantation from histocompatible sibling donors. For 62 patients in chronic phase, 26 in accelerated phase, and 27 in blast transformation, the actuarial survival at 3 years was 58%, 41%, and 25%, respectively. Actuarial probability of relapse was 3%, 12%, and 27%, respectively.
View Article and Find Full Text PDFA prospective randomised trial was performed in patients given HLA-identical sibling bone marrow transplants for haematological malignancy comparing the combination of cyclosporin and methotrexate (CM) (n = 20) with the combination of cyclosporin, methotrexate and prednisolone (CMP) (n = 21) as prophylaxis for graft-versus-host disease (GVHD). There was no significant differences between the two arms for the incidence of acute GVHD grades I-IV, acute GVHD grades II-IV, chronic GVHD, interstitial pneumonitis, relapse, survival and disease-free survival. The actuarial incidence of acute GVHD grades II-IV in the CMP group was 10% and in the CM group 15% (ns).
View Article and Find Full Text PDFObjective: To present a case of severe heat stroke after Rugby League football.
Clinical Features: A 29-year-old Rugby League forward with a mild infection of the upper respiratory tract collapsed while playing football in late March, when the ambient temperature was 24.1 degrees C and the relative humidity up to 73%.
Bone Marrow Transplant
September 1991
An acute pulmonary syndrome possibly representing acute graft-versus-host disease (GVHD) involving lung interstitium occurred in a patient given an allogeneic bone marrow transplant for haematological malignancy. He presented at day 34 with acute GVHD of skin and bowel, and this was associated with cough, dyspnoea and an asymmetrical change on chest X-ray. Lung biopsy demonstrated an interstitial and peribronchial lymphocytic infiltrate and acute bronchial epithelial degeneration.
View Article and Find Full Text PDFGanciclovir was given prophylactically to 25 patients receiving allogeneic bone marrow transplants for haematological malignancy. Patients who were seropositive for cytomegalovirus (CMV) pre-transplant were given ganciclovir both pre- and post-transplant. Those who were CMV seronegative, but who received marrow from a CMV seropositive donor, received ganciclovir post-transplant.
View Article and Find Full Text PDFBone Marrow Transplant
May 1991
Thirty-four patients receiving allogeneic bone marrow transplants as treatment for haematological malignancy were prospectively randomized to receive or not to receive bladder irrigation by indwelling urinary catheter during preparation for transplant. Twenty-two patients received busulphan and cyclophosphamide, four received busulphan, cyclophosphamide and irradiation, and eight received cyclophosphamide and total body irradiation. The actuarial incidence of haemorrhagic cystitis in those randomized to receive bladder irrigation was 48% for the whole group and 52% in those receiving busulphan and cyclophosphamide only.
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