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Biomedical subjects

J Matthews

Publications and source records attributed to J Matthews.

At least 19 recordsLinked to original sources
PubMed2005

Optimal scheduling to reduce morbidity of involved field radiotherapy with transplantation for lymphomas: a prospective Australasian Leukaemia and Lymphoma Group Study.

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.

Adolescent↗
PubMed2004

Androgen secretion by Rcho-1 cells is independent of extracellular glutamate concentration.

In primates, progesterone, secreted by the placenta, is important for the maintenance of pregnancy. Androstenedione, a progesterone metabolite, fulfils a similar role in the rodent. Prior work has suggested that glutamate sufficiency and subsequent oxidation is important to placental androgen synthesis, presumably because of the production of NADPH (Trophoblast Res (1993) 7, 77). Rcho-1 cells possess a phenotype similar to that of rat placental giant cells, and secrete androstenedione and progesterone when in the differentiated state (J Endocrinol (1996) 150, 161). Our objective was to determine whether extracellular glutamate concentrations impact hormone synthesis in Rcho-1 cells. Rcho-1 cells were kept in culture under differentiating conditions. Extracellular glutamate concentrations were varied from 0-5 mm, and hormone concentrations assayed by ELISA. Rcho-1 cells secreted both progesterone and androstenedione. There was no direct correlation between the extracellular concentration of glutamate and the secretion of either hormone. Inhibition of transaminases (aminooxyacetic acid) or of glutaminase (6-diazo-5-oxo-l-norleucine) did not alter hormone production. Therefore, extracellular glutamate concentrations did not impact progesterone or androstenedione secretion. These findings may relate to the central position of glutamate in a variety of metabolic pathways, making intracellular depletion of this amino acid difficult to accomplish, or may represent a species specific difference in regulation.

Androstenedione↗
PubMed2004

Evolving a lingua franca and associated software infrastructure for computational systems biology: the Systems Biology Markup Language (SBML) project.

Biologists are increasingly recognising that computational modelling is crucial for making sense of the vast quantities of complex experimental data that are now being collected. The systems biology field needs agreed-upon information standards if models are to be shared, evaluated and developed cooperatively. Over the last four years, our team has been developing the Systems Biology Markup Language (SBML) in collaboration with an international community of modellers and software developers. SBML has become a de facto standard format for representing formal, quantitative and qualitative models at the level of biochemical reactions and regulatory networks. In this article, we summarise the current and upcoming versions of SBML and our efforts at developing software infrastructure for supporting and broadening its use. We also provide a brief overview of the many SBML-compatible software tools available today.

Biochemistry↗
PubMed2004

Polymorphisms of the equine major histocompatibility complex class II DRA locus.

The full extent of the polymorphism of ELA-DRA in Equidae is not yet known. Given the apparent differences in DRA polymorphisms between Equidae and other species, the aims of this study were to more fully characterize ELA-DRA, determine the extent of gene polymorphism and establish the allele-frequency distribution. An allele reference panel for the second exon of ELA-DRA was established by sequence-based typing of 69 equine DNA samples consisting of various breeds of domestic horse (Equus caballus), together with donkeys (Equus asinus), Grant's zebras (Equus boehmi) and one onager (Equus hemionus). Five of the six previously reported alleles detected using single-strand conformation polymorphism were found: ELA-DRA*0101, ELA-DRA*0201, ELA-DRA*0301, ELA-DRA*0501 (Albright-Fraser DG et al. Polymorphism of DRA among equids. Immunogenetics 1996: 43: 315-7) and ELA-DRA*0601 (GenBank accession number AF5419361). In addition to the previously reported alleles, five novel ELA-DRA alleles were detected within the ELA-DRA allele reference panel. One of these was identified in E. caballus (ELA-DRA*JBH11), one in E. boehmi and E. hemionus (ELA-DRA*JBZ185) and three in E. asinus (ELA-DRA*JBD3, ELA-DRA*JBD17 and ELA-DRA*JBH45). A total of 565 equine DNA samples were screened using reference-strand-mediated conformation analysis, a double-stranded conformation-based mutation detection system that can be used to type existing ELA-DRA alleles and identify new variants. Based on our findings, at least 11 ELA-DRA alleles are now known to exist, and this level of polymorphism at the DRA locus appears to be unique to the genus Equus. Both the previously reported alleles and the new alleles displayed a species-specific distribution.

Amino Acid Sequence↗
PubMed2003

Patterns of clinical presentation, treatment, and outcome in patients with Waldenstrom's macroglobulinemia: a two-institution study.

Waldenstrom's macroglobulinemia (WM) is in the World Health Organization (WHO) classification considered to be a clinical syndrome rather than a specific pathologic diagnosis. The clinical manifestations associated with WM relate to direct tumor infiltration, hyperviscosity, and deposition of IgM in various tissues. The indications for and choice of treatment vary considerably and no generally accepted prognostic models exist. The clinical features, treatment, and prognosis of 72 patients with WM seen at one British (n = 36) and one Swedish (n = 36) academic center were therefore compared. Significantly more patients presented with a low albumin concentration (< v > 40 g/L, P <.001), anemia (hemoglobin < v > 120 g/L; P <.001), thrombocytopenia (< v > 150 x 10(9)/L; P <.05), hepatomegaly (P <.001), splenomegaly (P <.01), and lymphadenopathy (P <.01), at St Bartholomew's Hospital (SBH) in comparison to the Karolinska Hospital (KH). Fifty-six percent of SBH patients received chemotherapy immediately following diagnosis as compared to 14% at KH. The median overall survival of all patients was 6.3 years; 4.2 years and 11.0 years at SBH and KH, respectively (P <.001). In univariate analysis, anemia (hemoglobin < 120 g/L) and albumin < 35 g/L (but not <40 g/L) at diagnosis predicted a worse overall survival. The presence of hepatomegaly and/or splenomegaly and/or lymphadenopathy was significantly associated with anemia (P <.001) and hypoalbuminaemia (P <.001). The mean Morel score (including age, albumin, and cytopenias) of patients treated at SBH (2.6) was significantly higher than that of KH patients (1.6; P <.001). These findings illustrate the clinical heterogeneity of WM, most probably explained by differences in referral patterns, and in addition, indicate the need for establishing standard criteria for diagnosis, response to treatment, and prognostic features.

Adult↗
PubMed2003

Waldenstrom's macroglobulinemia: a retrospective analysis of 40 patients from 1972 to 2001.

From 1972 to 2001 at St. Bartholomew's Hospital 40 untreated Waldenstrom's macroglobulinemia (WM) patients received either chlorambucil (n = 23); cyclophosphamide, vincristine, and prednisolone (CVP) (n = 5); fludarabine-based therapy (n = 5); or other combination chemotherapy (n = 7). Twenty-eight patients (70%) responded to first-line therapy with overall response rates as follows: chlorambucil, 17/23 (74%); CVP, 4/5 (80%); fludarabine-based regimen, 2/5 (40%); other combinations, 5/7 (71%). Twenty patients were treated at progression with chlorambucil, of whom 10 (50%) responded again, 6/13 having had chlorambucil initially, and 4/7 having had other therapy. Although there was a trend towards a survival advantage for patients who responded to chlorambucil, this difference was not statistically significant. At 6 and 11 years, overall survival was 36% v 18% and 15% v 0% for responders and nonresponders, respectively. The overall pattern was the same for patients treated initially with chlorambucil as with other therapy. This retrospective analysis confirms that chlorambucil is an effective first-line agent in WM and has activity when used at subsequent relapse.

Adult↗
PubMed2003

Sustained release bupropion overdose: an important cause of prolonged symptoms after an overdose.

The case is reported of a patient who had taken a deliberate overdose of sustained release bupropion. The patient suffered from prolonged symptoms including seizures before fully recovering. The prescription of bupropion is encouraged as an aid to smoking cessation and it is probable that bupropion overdose will become more common. Emergency departments need to be aware that patients taking an overdose of sustained release bupropion may have a delayed onset and prolonged course of symptoms. The pharmacology, clinical features, and treatment of bupropion overdose are discussed.

Adult↗
PubMed2002

Distribution of androgen receptor mRNA expression and immunoreactivity in the brain of the green anole lizard.

Male courtship and copulation are androgen dependent in the green anole lizard, and female receptivity can be facilitated by testosterone. However, only a few, and relatively large, regions in the brain have been implicated in the control of these behaviours. In situ hybridization and immunohistochemistry were therefore used to determine in detail where androgens are likely to act in the brains of breeding males and females. A 697-bp fragment of the anole androgen receptor (AR) was cloned from total RNA isolated from the kidney, which contains the highly androgen-sensitive renal sex segment. The cloned fragment spanned part of the C, the entire D, and part of the E domains, and shared a high degree of similarity with the AR of various species. 35S-labelled antisense and sense probes were generated from the 697-bp fragment for use in in situ hybridization, and the AR antibody PG-21 was used for immunohistochemistry. Both sexes consistently had AR mRNA expression and immunoreactivity in areas associated with vertebrate reproductive behaviours and in motor areas of the brainstem. Interestingly, the PG-21 antibody produced labelling in both the nucleus and cytoplasm, including neuronal processes. The distribution of mRNA and immunoreactivity were comparable in males and females, and the amount of labelling was generally similar, although slightly greater in females. The expression pattern of AR in this species supports the idea that distribution is highly conserved among vertebrates, but that it probably does not dictate behavioural differences between the sexes in anoles.

Amino Acid Sequence↗
PubMed2002

The application of computer touch-screen technology in screening for psychosocial distress in an ambulatory oncology setting.

The objective of the study was to evaluate the acceptability and feasibility of computer touch-screen technology as a method for patients to report psychosocial functioning in an ambulatory cancer clinic. Patients participating in a randomized trial evaluating the use of self-reported psychosocial information in the clinical encounter were surveyed. The patients completed the Cancer Needs Questionnaire (CNQ), European Organization for the Research and Treatment of Cancer quality of life questionnaire (EORTC QLQ-C30) and the Beck Depression Inventory - Short Form (BDI) using a touch-screen computer. The time taken to complete the questionnaires was recorded electronically. Patients completed a seven-item pen and paper survey to assess acceptability of the process. Of the 450 patients, 244 (54%) were 60 years or older. Although over half the patients had no prior computer experience, nearly all found the touch screen easy to use and the instructions easy to understand. Each question was answered by at least 447 (99.3%) patients. The average time to complete the CNQ was 9.1 min, EORTC QLQ-C30 4.0 min and BDI 3.1 min. Factors influencing time to completion were prior use of computers, physical condition, education and overall level of needs. The study found that the use of computer touch-screen technology is an acceptable and efficient method for obtaining self-reported information on quality of life, cancer needs and psychological distress.

Adaptation, Psychological↗
PubMed2002

Genetic susceptibility to Hodgkin's disease and secondary neoplasias: FISH analysis reveals patients at high risk of developing secondary neoplasia.

BACKGROUND: Cytotoxic drugs administered before high-dose therapy (HDT) represent a significant factor in the development of leukemic complications in patients with lymphoid malignancies. This retrospective study was used to detect evidence of abnormal therapy-related myelodysplasia/secondary acute myeloid leukaemia (tMDS/sAML) clones before HDT in a subset of patients who subsequently developed secondary neoplasia. PATIENTS AND METHODS: 230 patients with non-Hodgkin's lymphoma (NHL) underwent HDT comprising cyclophosphamide and total body irradiation (TBI) with autologous hematopoietic progenitor-cell support. Thirty-three patients have developed tMDS/sAML and 20 of these were screened for the presence of emerging therapy-related abnormalities before HDT. A further 24 patients without evidence of secondary neoplasia were screened using fluorescence in situ hybridisation (FISH). RESULTS: Significant levels of abnormal cells were identified in 20/20 patients screened who have developed secondary neoplasia compared with only three of 24 patients in the HDT control group who have not. The latter three patients have since died. CONCLUSIONS: The triple FISH assay was developed to detect loss of chromosomal material from 5q31, 7q22 and 13q14. It can potentially identify those patients at risk of alkylating agent-induced leukaemia before they proceed to HDT. Used in a prospective manner, the triple FISH assay could permit more informed clinical management.

Acute Disease↗
PubMed2001

Randomized trial of coordinated psychosocial interventions based on patient self-assessments versus standard care to improve the psychosocial functioning of patients with cancer.

PURPOSE: To determine whether making patient-reported cancer needs, quality-of-life (QOL), and psychosocial information available to the health care team, allowing coordinated specifically targeted psychosocial interventions, resulted in reduced cancer needs, improved QOL, and increased satisfaction with care received. METHODS: Self-reported cancer needs, QOL, and psychosocial information was collected from 450 people with cancer, using standardized questionnaires via a touch-screen computer. For a randomly chosen two thirds, this information was made available to the health care team who coordinated targeted psychosocial interventions. Information from the remaining one third was not seen. Patients were assessed 2 and 6 months after randomization for changes in their cancer needs, QOL, and psychosocial functioning and satisfaction with overall care received. RESULTS: There were no significant differences between the two arms with respect to changes in cancer needs, QOL, or psychosocial functioning between the baseline and follow-up assessments, nor with respect to satisfaction with care. However, for the subgroup of patients who were moderately or severely depressed at baseline, there was a significant reduction in depression for the intervention arm relative to the control arm at the 6-month assessment (P =.001). CONCLUSION: Making patient-reported cancer needs, QOL, and psychosocial data available to the health care team at a single consultation together with coordinated psychosocial interventions does not seem to reduce cancer needs nor improve QOL, psychosocial functioning, or satisfaction with the care received. However, identification of patients with moderate or severe levels of depression may be valuable in reducing subsequent levels of depression.

Adaptation, Psychological↗
PubMed2001

The Immune Tolerance Network: tolerance at the crossroads.

Immune tolerance therapies are designed to reprogramme immune cells in a highly specific fashion in order to eliminate pathogenic responses but preserve normal immune function. A concept that has tantalized immunologists for decades, tolerogenic therapies would replace current lifelong immunosuppressive regimens and their often debilitating side-effects with short-term immunosuppressive regimens and their often debilitating side-effects with short-term, effective cures. Significant advances have been made over the past decade that have provided a more detailed understanding of the molecular events associated with T-cell recognition and activation. Unprecedented opportunities to test these approaches in a variety of human diseases have now emerged. As a result of these advances, the Immune Tolerance Network (ITN), a group of 70 expert immunologists spanning multiple disciplines, has been created to identify and promote the use of tolerogenic therapies in the clinic. Using a unique interactive approach designed to speed the development of clinical tolerance therapies, the ITN is examining new and innovative therapeutic approaches and bioassays in a range of autoimmune diseases and transplantation settings, as well as asthma and allergies. This work has been funded by the National Institutes of Health (in collaboration with the Juvenile Diabetes Foundation International).

Asthma↗
PubMed2001

Detection of chromosome abnormalities pre-high-dose treatment in patients developing therapy-related myelodysplasia and secondary acute myelogenous leukemia after treatment for non-Hodgkin's lymphoma.

PURPOSE: To assess whether pre-high-dose therapy (HDT)-related factors play a critical role in the development of therapy-related myelodysplasia (tMDS) or secondary acute myelogenous leukemia (sAML). PATIENTS AND METHODS: Twenty-nine of 230 patients with a primary diagnosis of non-Hodgkin's lymphoma (NHL) developed tMDS/sAML after HDT comprising cyclophosphamide and total-body irradiation (TBI) supported by autologous hematopoietic progenitor cells. G-banding and fluorescence in-situ hybridization (FISH) were used to detect clonal cytogenetic abnormalities. RESULTS: The majority of patients showed complex karyotypes at diagnosis of tMDS/sAML containing, in particular, complete or partial loss of chromosomes 5 and/or 7. Using single locus-specific FISH probes, significant levels of clonally abnormal cells were found before HDT in 20 of 20 tMDS/sAML patients screened, compared with three of 24 patients screened who currently have not developed tMDS/sAML, at a median follow-up of 5.9 years after HDT. CONCLUSION: Prior cytotoxic therapy may play an important etiologic role and may predispose to the development of tMDS/sAML. Using a triple FISH assay designed to detect loss of chromosomal material from 5q31, 7q22, or 13q14, significant levels of abnormal cells can be detected before HDT and may predict which patients are at increased risk of developing secondary disease. Further prospective evaluation of this FISH assay is warranted to determine its predictive power in this setting.

Chromosome Aberrations↗
PubMed2001

Effects of glycosylated recombinant human granulocyte colony-stimulating factor after high-dose cytarabine-based induction chemotherapy for adult acute myeloid leukaemia.

The Australian Leukaemia Study Group (ALSG) investigated whether G-CSF would accelerate haemopoietic recovery after induction treatment for acute myeloid leukaemia (AML) intensified with high-dose cytarabine, and therefore improve response rates and survival. Patients were randomised to receive lenograstim (glycosylated recombinant human G-CSF) 5 microg per kg body weight subcutaneously daily from day 8 after starting chemotherapy, or no cytokine, following chemotherapy with cytarabine 3 g/m2 every 12 h on days 1, 3, 5, and 7, together with idarubicin 9 or 12 mg/m2 on days 1, 2, and 3, plus etoposide 75 mg/m2 on days 1 to 7 inclusive. Patients had untreated AML, and were aged 16 to 60 years. Overall, 54 evaluable patients were randomised to receive lenograstim and 58 to no cytokine. Patients in the lenograstim arm had a significantly shorter duration of neutropenia <0.5 x 10(9)/l compared to patients in the no cytokine arm (median 18 vs 22 days; P = 0.0005), and also shorter duration of total leucopenia <1.0 x 10(9)/l (17 vs 19 days; P = 0.0002), as well as a reduction in duration of treatment with therapeutic intravenous antibiotics (20 vs 24 days; P= 0.015) and a trend to reduced number of days with fever >38.0 degrees C (9 vs 12 days; P = 0.18). There were no differences between the two groups in platelet recovery, red cell or platelet transfusions, or non-haematological toxicities. For patients achieving CR after their first induction course, a reduction in the time to the start of the next course of therapy was observed in the lenograstim arm, from a median of 40.5 days to a median of 36 days (P = 0.082). The overall complete response rates to chemotherapy were similar, 81% in the lenograstim arm vs 75% for the no cytokine arm (P = 0.5), and there was no significant difference in the survival durations. We conclude that the granulopoietic stimulating effect of G-CSF is observed after induction therapy for AML intensified by high-dose cytarabine, resulting in an improvement in a number of clinically important parameters with no major adverse effects.

Acute Disease↗
PubMed2001

Cluster of tuberculosis cases in North Carolina: possible association with atomizer reuse.

BACKGROUND: Three patients with identical strains of M tuberculosis (TB) underwent bronchoscopy on the same day at hospital A. METHODS: We reviewed each patient's clinical history, hospital A's infection control practices for bronchoscopies, and specimen and isolate handling at each of 3 laboratories involved. We searched for possible community links between patients. Restriction fragment length polymorphism was performed on TB isolates. RESULTS: The first patient who underwent bronchoscopy had biopsy-confirmed granulomatous pulmonary TB. A sputum sample collected from the third patient 6 weeks after the bronchoscopy produced an isolate with an identical restriction fragment length polymorphism pattern to isolates collected during the bronchoscopies. No evidence existed for community transmission or laboratory contamination; the only common link was the bronchoscopy. Different bronchoscopes were used for each patient. Hospital ventilation and wall-suctioning were functioning well. Respiratory technicians reported sometimes reusing the nozzles of atomizers on more than one patient. A possible mechanism for transmission was contamination from the first patient of the atomizer if it was used to apply lidocaine to the pharynx and nasal passages of other patients. CONCLUSIONS: A contaminated atomizer may have caused TB transmission during bronchoscopy. Hospital A changed to single-use atomizers after this investigation.

Aged↗
PubMed2001

Long-term consequences of severe closed head injury on episodic memory.

This is the first systematic investigation of the very long-term effects of severe closed head injury (CHI) on objective measures of memory, and the first to employ both a normal control group and an 'other injury' control group consisting of spinal cord injury (SCI) patients. The CHI group displayed significantly poorer performance on every memory measure, and the effect sizes were large. This impairment in episodic memory is neither due to pre-injury nor post-injury differences between CHI and normal control subjects because the same differences were found when the CHI group was compared to a group of SCI patients. The findings demonstrate severe impairment in learning and retention many years after sustaining a severe CHI, which is likely in part due to the bilateral hippocampal damage shown in neuropathological studies. This life-long memory impairment needs to be addressed by community service programs.

Adult↗
PubMed2001

Treating systemic diseases via the lung.

Inhalation of pharmacologically active substances for medicinal, social, or recreational purposes has been prevalent for centuries but experience of exploiting the lung as a route of delivery for treatment of nonrespiratory diseases is limited. Despite the success of current applications such as anesthetics, the utility of the lung for drug delivery is not well appreciated, despite advantages such as rapid onset of action. Two drawbacks are the relatively poor efficiency of current inhalation devices, especially for large molecules, and the poor patient acceptability of inhalers. Advances now being made in pulmonary delivery technology may provide the impetus needed for the development of new inhaled presentations of drugs such as peptide hormones and other biologically derived molecules. Molecules of various sizes can be delivered in clinically relevant quantities via the lung. In vitro methods show that lipophilic drugs are absorbed through the alveolar membrane more quickly. Early work in animal models has already shown that absorption of analgesic and antiinflammatory drugs that are not well absorbed orally can be improved by delivering them by inhalation. This work may soon give rise to new formulations for therapeutic use.

Administration, Inhalation↗