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Biomedical subjects

M Thomas

Publications and source records attributed to M Thomas.

At least 289 records · Page 16Linked to original sources
PubMed1999

Activation of the kallikrein-kinin system in hemodialysis: role of membrane electronegativity, blood dilution, and pH.

BACKGROUND: The kallikrein-kinin system activation by contact with a negatively charged surface has been promulgated to be responsible for hypersensitivity reactions. However, to explain the low frequency and heterogeneity of hypersensitivity reactions, we hypothesized that not only the electronegativity of the membrane, but also other physicochemical parameters could influence the activation of the contact phase system of plasma assessed by the measurement of kallikrein activity and bradykinin concentration. METHODS: Plasma kallikrein activity using chromogenic substrate (S2302) and plasma bradykinin concentration (enzyme immuno assay) were measured during the perfusion of human plasma (2.5 ml/min) through minidialyzers mounted with six different membranes [polyacrylonitrile (PAN) from Asahi (PANDX) and from Hospal (AN69), polymethylmethacrylate (PMMA) from Toray, cellulose triacetate (CT) from Baxter, cuprophane (CUP) from Akzo and polysulfone (PS) from Fresenius]. RESULTS: A direct relationship was shown between the electronegativity of the membrane assessed by its zeta potential and the activation of plasma during the first five minutes of plasma circulation. With the AN69 membrane, the detection of a kallikrein activity in diluted plasma but not in undiluted samples confirmed the importance of a protease-antiprotease imbalance leading to bradykinin release during the first five minutes of dialysis. With PAN membranes, the use of citrated versus heparinized plasma and the use of various rinsing solutions clearly show a dramatic effect of pH on the kallikrein activity and the bradykinin concentration measured in plasma. Finally, increasing the zeta potential of the membrane leads to a significant increase of plasma kallikrein activity and bradykinin concentration. CONCLUSIONS: Our in vitro experimental approach evidences the importance of the control of these physicochemical factors to decrease the activation of the contact system.

Acrylic Resins↗
PubMed1999

Interleukin-2-activated autologous bone marrow and peripheral blood stem cells in the treatment of acute leukemia and lymphoma.

In this pilot trial of interleukin (IL)-2-treated autologous bone marrow (BM) and peripheral stem cell (PSC)-supported high-dose chemoradiotherapy, we report 36 patients with poor-prognosis leukemia and lymphoma who received BM and/or granulocyte colony-stimulating factor (G-CSF)-mobilized autologous PSCs that had been exposed to IL-2 for 24 hours ex vivo. Patients then received IL-2 by low-dose continuous intravenous (i.v.) infusion until hematologic reconstitution and then by intermediate-dose continuous i.v. infusion for six 2-week maintenance cycles given at 1-month intervals. The median Day to neutrophils over 500/microL was 22 with BM and 10 with PSCs (p = 0.01). The median Day to platelets >20,000/microL was 50 for BM and 25 for PSCs, and to platelets >50,000/microL was 138 for BM and 34 for PSCs (p not significant). After the first three patients received IL-2 at 2 mIU x m(-2) x day(-1) and had slow reconstitution, four patients were treated without IL-2 until the maintenance phase following reconstitution. The remaining 29 patients received the initial "post-infusion" IL-2 at 1 mIU x m(-2) x day(-1). Toxicities associated with the infusion of IL-2-activated cells consisted of chills and fever in about one-half of the patients and transient hypotension in 12%. Low-dose IL-2 by continuous i.v. infusion in the early posttransplant period was associated with exacerbation of fever, diarrhea, and altered mental status in a minority of patients. The major dose-limiting toxicities of maintenance IL-2 were fever, fatigue, gastrointestinal symptoms, skin rash, and dyspnea. Among 24 lymphoma patients, nine are in continuous complete remission (CCR) from 18-48 months, and 15 have died (12 due to relapse and three of therapy-related toxicities). Of 12 acute leukemia patients, two with acute lymphoblastic leukemia (ALL) are in CCR at 38 and 43 months, and one patient who was in cytogenetic but not molecular remission of Philadelphia chromosome-positive ALL died of progressive leukemia at Day 108. Three of nine with myeloid leukemia are in CCR at 21, 46, and 53 months; one is in hematologic and cytogenetic remission of acute promyelocytic leukemia at 55 months with multiple new cytogenetic abnormalities; one is alive at 54 months with pancytopenia after incomplete hematologic recovery followed by multiple new cytogenetic abnormalities (myelodysplasia); and one had an unrelated donor transplant after relapsing 4 months following protocol therapy. One myeloid leukemia patient remains without evidence of relapse, but is transfusion-dependent at 15 months following transplant.

Acute Disease↗
PubMed1999

Assessment of wood utility pole climbability using psychophysical and mechanical measurements.

The issue of climbability has been raised on several occasions for more than a decade in North America. Presently, climbability is estimated from the pole hardness measured by the Pilodyn measurements (6 J). However, the use of Pilodyn measurements to discriminate the pole hardness value is criticized by climbers, who claim that the Pilodyn hardness measurement is affected by species-treatment combinations and that it does not reflect gaff penetration or climbability. Furthermore, climbability evaluations have been conducted in which test poles were climbed by linemen, and corresponding subjective ratings were recorded. However, the ability of psychophysical measurements to accurately discriminate close hardness pole values and to differentiate species-treatment combinations at specific hardness levels have not yet been fully documented. The aim of this study is to evaluate the psychophysical perception of linemen and the mechanical measurements of gaff penetration and gaff impact during the climbing of different wood species and treatment combinations in order to compare these results with Pilodyn measurements within a precise range of pole hardnesses, to study the relationships between these variables, and, finally, to propose various design guidelines for the development of a better tool for the evaluation of climbability.

Adult↗
PubMed1999

Human papillomavirus (HPV) E6 interactions with Bak are conserved amongst E6 proteins from high and low risk HPV types.

Human papillomavirus (HPV) replication occurs in terminally differentiating epithelium, and requires the activation of cellular DNA replication proteins. Unscheduled DNA replication can result in the induction of apoptosis, and the viral E6 protein induces the degradation of p53 to prevent this. It has recently been shown that HPV-18 E6 can also stimulate the degradation of Bak, a pro-apoptotic member of the Bcl-2 family. This report shows that the E6 proteins from HPV-18, HPV-16 and HPV-11 can all bind to Bak in vitro, stimulate its degradation in vivo and reduce Bak-induced apoptosis. However, the non-oncogenic HPV-11 E6 is less effective than the oncogenic E6 proteins in each of these assays, indicating that the ability of HPV to circumvent the apoptosis induced by Bak may contribute to the oncogenic potential of the virus.

Apoptosis↗
PubMed1999

Home visits by an occupational therapist for assessment and modification of environmental hazards: a randomized trial of falls prevention.

OBJECTIVE: To determine whether occupational therapist home visits targeted at environmental hazards reduce the risk of falls. DESIGN: A randomized controlled trial. SETTING: Private dwellings in the community in Sydney, Australia. PARTICIPANTS: A total of 530 subjects (mean age 77 years), recruited primarily before discharge from selected hospital wards. INTERVENTION: A home visit by an experienced occupational therapist, who assessed the home for environmental hazards and facilitated any necessary home modifications. MEASUREMENTS: The primary study outcome was falls, ascertained over a 12-month follow-up period using a monthly falls calendar. RESULTS: Thirty six percent of subjects in the intervention group had at least one fall during follow-up, compared with 45% of controls (P = .050). The intervention was effective only among subjects (n = 206) who reported having had one or more falls during the year before recruitment into the study; in this group, the relative risk of at least one fall during follow-up was 0.64 (95% confidence interval, 0.50-0.83). Similar results were obtained when falls data were analyzed using survival analysis techniques (proportional and multiplicative hazards models) and fall rates (mean number of falls per person per year). About 50% of the recommended home modifications were in place at a 12-month follow-up visit. CONCLUSIONS: Home visits by occupational therapists can prevent falls among older people who are at increased risk of falling. However, the effect may not be caused by home modifications alone. Home visits by occupational therapists may also lead to changes in behavior that enable older people to live more safely in both the home and the external environment.

Accidental Falls↗
PubMed1999

Two polymorphic variants of wild-type p53 differ biochemically and biologically.

The wild-type p53 protein exhibits a common polymorphism at amino acid 72, resulting in either a proline residue (p53Pro) or an arginine residue (p53Arg) at this position. Despite the difference that this change makes in the primary structure of the protein resulting in a difference in migration during sodium dodecyl sulfate-polyacrylamide gel electrophoresis, no differences in the biochemical or biological characteristics of these wild-type p53 variants have been reported. We have recently shown that p53Arg is significantly more susceptible than p53Pro to the degradation induced by human papillomavirus (HPV) E6 protein. Moreover, this may result in an increased susceptibility to HPV-induced tumors in homozygous p53Arg individuals. In further investigating the characteristics of these p53 variants, we now show that both forms are morphologically wild type and do not differ in their ability to bind to DNA in a sequence-specific manner. However, there are a number of differences between the p53 variants in their abilities to bind components of the transcriptional machinery, to activate transcription, to induce apoptosis, and to repress the transformation of primary cells. These observations may have implications for the development of cancers which harbor wild-type p53 sequences and possibly for the ability of such tumors to respond to therapy, depending on their p53 genotype.

Animals↗
PubMed1999

"First aid for scalds" campaign: reaching Sydney's Chinese, Vietnamese, and Arabic speaking communities.

OBJECTIVES: As a serious yet preventable problem, scald injuries in children have been a priority for prevention in Australia and other developed countries. Not only can the occurrence of scalds be prevented, but immediate first aid treatment offers an effective method for secondary prevention, reducing the severity of scalds. Despite the success of scald prevention initiatives, local evidence suggested that first aid knowledge was lacking in some minority ethnic groups. To redress this gap, the "First Aid for Scalds" campaign for those from a non-English speaking background was specifically targeted to three ethnic groups (Vietnamese, Chinese, and Arabic), with the aim of increasing the proportions of parents and caregivers who had correct knowledge of first aid treatment for scalds. The primary strategy was a media campaign, including advertisements on ethnic radio and in ethnic newspapers. METHODS: The evaluation design included formative research and impact evaluation. The impact evaluation study involved random population based telephone surveys with each of the three language groups, before and after the campaign, to assess the reach and effectiveness of the campaign. RESULTS: After the campaign, there were significant increases in the proportion of people who knew the correct first aid treatment for scalds. There were substantial variations in campaign recall and knowledge between each of the three language groups. The largest improvement was found in the Vietnamese group. CONCLUSION: The association between campaign recall and increase in correct knowledge, and the absence of any similar interventions during the campaign period, give credence to the conclusion that the changes observed were a result of the campaign. The results demonstrate the value of community based injury prevention campaigns specifically targeting linguistically diverse communities.

Accident Prevention↗
PubMed1999

Point source sulphur dioxide peaks and hospital presentations for asthma.

OBJECTIVE: To examine the effect on hospital presentations for asthma of brief exposures to sulphur dioxide (SO2) (within the range 0-8700 micrograms/m3) emanating from two point sources in a remote rural city of 25,000 people. METHODS: A time series analysis of SO2 concentrations and hospital presentations for asthma was undertaken at Mount Isa where SO2 is released into the atmosphere by a copper smelter and a lead smelter. The study examined 5 minute block mean SO2 concentrations and daily hospital presentations for asthma, wheeze, or shortness of breath. Generalised linear models and generalised additive models based on a Poisson distribution were applied. RESULTS: There was no evidence of any positive relation between peak SO2 concentrations and hospital presentations or admissions for asthma, wheeze, or shortness of breath. CONCLUSION: Brief exposures to high concentrations of SO2 emanating from point sources at Mount Isa do not cause sufficiently serious symptoms in asthmatic people to require presentation to hospital.

Air Pollutants↗
PubMed1999

Molecular, serological and population studies of the alleles and products of HLA-B*41.

The HLA-B41 specificity was first identified over 25 years ago and, although both serological and biochemical studies have suggested its subdivision, it is only recently that two HLA-B*41 alleles (B*4101 and B*4102) have been identified and sequenced. We designed three oligonucleotide primers, combined in two mixtures to define these alleles by PCR using sequence-specific primers (PCR-SSP) in a random normal population of 9,464 HLA-A, B, DR, DQ typed Northern European Caucasoid donors from the Welsh Bone Marrow Donor Registry. The HLA-B41 phenotype frequency was 0.835%, and of the 79 HLA-B41 subjects 22 (27.85%) were B*4101 and 57 (72.15%) were B*4102. The phenotype frequencies of B*4101 and B*4102 were 0.232 and 0.602%, respectively, and the gene frequencies were 0.00116 and 0.00301, respectively. Formal two-locus linkage disequilibrium (LD) analysis demonstrated significant associations between B*4101 and A30 and DR11, and between B*4102 and A66 and DR13. LD analysis of three loci showed significant associations between B*4101, DR7, DQ2 and B*4101, DR11, DQ7 (DQB1*0301/0304) and between HLA-A3, B*4102, DR13; A66, B*4102, DR7; A66, B*4102, DR13; B*4102, DR13, DQ6 and B*4102, DR13, DQ7. Examination of the HLA phenotypes (including HLA-C) of the B*41 subjects, together with the LD analysis findings, suggested four different HLA haplotypes bearing B*4101 and five B*4102 haplotypes. The most frequent B*4101 haplotype was: HLA- A30 or other A allele, Cw*1701, B*4101, DRB1*1102, DQB1*0301 and the most freqent B*4102 haplotype was: A*6601 or A3 or other A allele, Cw*1701, B*4102, DRB1*1303, DQB1*0301. In addition, the well-known association of A66 with B41 was between A*6601 and B*4102, and although both B*41 alleles were commonly in association with Cw*1701, B*4101 was found with Cw*07. One-dimensional isoelectric focusing (1D-IEF) analysis of HLA-B proteins from 2 B*4101 and 2 B*4102 subjects clearly showed that the B41.1 and B41.2 1D-IEF variants, identified in the 10th International Histocompatibility Workshop, corresponded to B*4101 and B*4102 products, respectively. Serological titration studies, with 59 lymphocytotoxic pregnancy antisera, containing an HLA-B41 component and stimulated by up to five different HLA-B specificities, were unable to differentiate the two groups of B*41 subjects. This suggests that partition of the HLA-B41 specificity will not normally be achieved by classical serological methods. It is suggested that the previous alleged serological subdivision of HLA-B41 was founded on the unwitting use of antisera detecting the HLA-Cw*17 products.

Alleles↗
PubMed1999

Trimodality therapy in stage III non-small cell lung cancer: prediction of recurrence by assessment of p185neu.

In a trimodality treatment approach for stage III non-small cell lung cancer the prognostic impact of pretherapeutic p185neu assessment was evaluated. Fifty-four patients were admitted to chemotherapy followed by twice-daily radiation with concomittant low-dose chemotherapy and subsequent surgery. Immunohistochemical assessment of p185neu expression was performed in paraffin-embedded mediastinal lymph node metastases, by mediastinoscopy biopsy prior to therapy. Paraffin-embedded biopsies of mediastinal lymph node metastases were available in 33 cases. Seven out of eight patients with positive p185neu staining developed distant metastases, in contrast to seven out of 25 negative cases. Expression of p185neu in mediastinal lymph node metastases was a significant predictor for progression-free survival (p=0.047) and resulted mainly from significant differences in metastases-free survival (p185neu-positive versus p185neu-negative: median, 11 versus 19 months; 2- and 3-yr rates, 13% and 0% versus 40% and 32%; p=0.04). On the basis of these preliminary results it was concluded that further evaluation of p185neu expression in trials on neoadjuvant and adjuvant therapy is warranted. When the prognostic impact of p185neu in such trials with larger patient numbers is confirmed, this may contribute to the identification of stratification variables for future treatment approaches of non-small cell lung cancer.

Adult↗
PubMed1999

Impact of preoperative bimodality induction including twice-daily radiation on tumor regression and survival in stage III non-small-cell lung cancer.

PURPOSE: The objective of this prospective study was to assess the feasibility, toxicity, and efficacy of an intensive trimodality approach in stage III non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Fifty-four patients with NSCLC and biopsy-proven N2 nodes (IIIA; n = 25) or N3 nodes or T4 lesions (IIIB; n = 29) were administered two initial cycles of ifosfamide, carboplatin, and etoposide; subsequent radiotherapy (45 Gy, twice-daily 1.5 Gy) with concurrent carboplatin and vindesine; and surgery if the patient's disease was resectable or conventional radiotherapy (16 Gy, 2 Gy/d) if the patient's disease was not resectable or incompletely resectable. RESULTS: Thirty-seven patients (69%) responded to preoperative induction. Forty of 54 patients (74%) had disease that was resectable, with 34 (63%) complete resections (R0). A substantial pathologic response (tumor regression [TR] > 90%) was achieved in 27 of 54 patients (50%) and is revealed as an independent predictor for long-term survival after surgery. Five treatment-related deaths (9%) occurred. With a median follow-up period of 44 months, calculated survival rates at 3 years were 35% for patients with stage IIIA disease, 26% for patients with stage IIIB disease, and 56% for patients with R0 disease and TR > 90%. CONCLUSION: This trimodality approach is feasible and results in encouraging 3-year survival rates in prognostically unfavorable patients with stage III NSCLC. Patients experiencing a 90% degree of pathologic TR were most likely to achieve long-term survival.

Adult↗
PubMed1999

Two-dimensional kinetic models for radiotherapy planning quality assurance.

For treatment planning, the visualization of the direction and orientation of a beam, specified by a set of machine angles, can sometimes be very difficult. A set of simple two-dimensional kinetic models has been prepared. These show the angular and field conventions of the local linear accelerators.

Audiovisual Aids↗
PubMed1999

A model simulator for radiotherapy treatment planning and checking.

For a linear accelerator the direction and orientation of a beam is specified uniquely by a set of gantry, turntable and collimator angles. Sometimes, particularly for 3D planning, it is very difficult for the planner or plan checker to visualize the set-up of the treatment machine from the angles specified for each beam. This note describes a simple line-of-sight model that can be used for planning and checking the radiotherapy geometry prior to simulator verification.

Humans↗
PubMed1999

Adverse reactions to radiocontrast media in an Indian population.

This study was conducted to determine the epidemiological characteristics and clinical presentation of adverse reactions to intravenous radiocontrast media (CM) in patients of Indian origin. 379 of 1798 patients who received either sodium iothalamate or sodium meglumine diatrizoate developed adverse reactions (i.e. 21.08% of patients). The incidence of mild, moderate and severe adverse reactions were 19.47%, 1.33% and 0.28%, respectively. One patient who developed a severe reaction expired. There were no differences in the incidence of adverse reactions according to gender (males 21.2%; females 20.8%; p = 0.907) or age (p = 0.876). The incidence of adverse reactions was significantly higher in patients with a history of previous reactions (45.5%) than in those with no history (20.9%; p = 0.046). The incidence of reactions was also significantly higher in patients with a history of predisposing factors such as bronchial asthma (69.2%) and diabetes mellitus (60.0%) than in those without such a history (20.6%; p = 0). The incidence of adverse reactions in patients who received premedication prior to CM administration because of a history of predisposing factors (21.4%) was not significantly different from that in patients who were not premedicated (21.2%; p = 0.974), a result probably due to inadequate premedication used in the study. The skin was the most commonly affected site of reaction.

Adolescent↗