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Biomedical subjects

M Hamilton

Publications and source records attributed to M Hamilton.

At least 55 records · Page 3Linked to original sources
PubMed2000

Immigrant and Native-born Mexican-American parents' involvement in a public school: a preliminary study.

Mexican-American parents of Texas elementary school students were surveyed to compare the types of school involvement in which immigrant and U.S.-born parents engage. Those completing the questionnaire included 246 mothers and 39 fathers born in Mexico as well as 95 mothers and 13 fathers born in the United States. More immigrant parents than U.S.-born parents indicated they helped their children with school work, attended school board meetings, volunteered at school, participated in parent-teacher conferences, went to school functions, served as room mother, engaged in school fundraising, and were present during parent advisory committee meetings.

Adult↗
PubMed2000

Imaging and phase I study of 111In- and 90Y-labeled anti-LewisY monoclonal antibody B3.

B3 is a murine monoclonal antibody (mAb) that recognizes a LewisY carbohydrate antigen present on the surface of many carcinomas. An imaging and Phase I trial was performed to study the ability of 111In-mAb B3 to image known metastasis and determine the maximum tolerated dose (MTD), dose-limiting toxicity (DLT), kinetics, and biodistribution of 90Y-mAb B3. Patients (n = 26) with advanced epithelial tumors that express the LewisY antigen were entered. All patients received 5 mCi of 111In-mAb B3 for imaging. 90Y-mAb B3 doses were escalated from 5 to 25 mCi in 5-mCi increments. 111In-mAb B3 and 90Y-mAb B3 were coadministered over a 1-h infusion. Definite tumor imaging was observed in 20 of 26 patients. Sites imaged included lung, liver, bone, and soft tissues. The MTD of 90Y-mAb B3 was determined to be 20 mCi. The DLTs were neutropenia and thrombocytopenia. Tumor doses ranged from 7.7 to 65.1 rad/mCi. 111In- and 90Y-mAb B3 serum pharmacokinetics (n = 23) were found to be similar. The amount of B3 administered (5, 10, and 50 mg) did not alter the pharmacokinetics. Bone marrow biopsies (n = 23) showed 0.0038+/-0.0016% of injected dose/gram for 111In-mAb B3 compared to 0.0046+/-0.0017% of injected dose/gram for 90Y-mAb B3 (P = 0.009). When given to patients with carcinomas that express the LewisY antigen, 111In-mAb B3 demonstrated good tumor localization. The MTD of 90Y-mAb B3 is 20 mCi, with myelosuppression as the DLT. Higher doses of radioactivity need to be delivered to achieve an antitumor effect. Humanized mAb B3 is being developed for evaluation in radioimmunotherapy. A clinical trial to explore the use of higher doses of 90Y-mAb B3 with autologous stem cell support is planned.

Adult↗
PubMed2000

Antitumor efficacy, pharmacokinetics, and biodistribution of NX 211: a low-clearance liposomal formulation of lurtotecan.

Lurtotecan is a clinically active water-soluble camptothecin analogue that has been formulated into a low-clearance unilamellar liposome, NX 211. Comparative studies between free drug and NX 211 have been performed assessing pharmacokinetics in nude mice, tissue distribution in tumor-bearing mice, and antitumor efficacy in xenografts. Compared with lurtotecan, NX 211 demonstrated a significant increase in plasma residence time and a subsequent 1500-fold increase in the plasma area under the drug concentration curve. The volume of distribution was also greatly restricted, suggesting altered tissue distribution. Evaluation of tissues 24 h after administration of either [14C]NX 211 or [14C]lurtotecan to ES-2 tumor-bearing mice demonstrated a 40-fold increase in radiolabeled compound in the tumors of NX 211-treated mice compared with mice treated with lurtotecan. In single-dose efficacy studies, NX 211 produced a consistent 3-fold or greater increase in therapeutic index compared with lurtotecan in both the KB and ES-2 xenograft models. When compared at equitoxic levels in repeat-dose efficacy studies, NX 211 generated durable cures lasting >60 days and a 2-8-fold increase in log10 cell kill, compared with lurtotecan and topotecan, respectively. Together, these data demonstrate that NX 211 has significant therapeutic advantage over lurtotecan and that the improved antitumor activity is consistent with increased exposure and enhanced drug delivery to tumor sites.

Animals↗
PubMed2000

Domestic swine model for the assessment of chemical warfare agent-anesthetic interactions: some effects of sulfur mustard.

A domestic swine model was developed to examine the interaction of chemical warfare agents with anesthetics and other drugs used during general anesthesia. Animals were fully instrumented, and clinically relevant physiological parameters were monitored throughout the experimental procedures. Exposure of animals under halothane anesthesia to the chemical warfare agent sulfur mustard (HD; 1 mg/kg intravenous) produced mild signs of systemic intoxication during the subsequent 5 hours. Induction doses of ketamine 1 hour after HD exposure resulted in periods of profound apnea, with continued respiratory distress for the next 2 hours. When animals were treated with HD 1 hour after the initiation of ketamine anesthesia, severe and persistent convulsion-like muscular activity was observed within 45 minutes of HD administration. This nonpurposeful activity was not ameliorated by diazepam but was dramatically reduced or eliminated by resumption of halothane anesthesia. Treatment of HD-intoxicated pigs with succinylcholine produced a prolonged apnea resulting in death. In these apparently mildly HD-intoxicated animals, the introduction of ketamine or succinylcholine can rapidly induce potentially life-threatening situations.

Anesthesia, General↗
PubMed2000

The incidence of sports-related facial trauma in children.

We conducted a survey of physician members of the American Academy of Facial Plastic and Reconstructive Surgery to determine the incidence and nature of facial traumas seen in their practices. We solicited information on the anatomic location of each injury, the severity of the trauma, and whether the injury occurred during a sports activity. According to the responses, 21% of facial fractures and 29% of nasal fractures were experienced by patients aged 17 years and younger who were participating in sports. We believe that many such injuries can be prevented with greater use of protective equipment.

Adolescent↗
PubMed2000

Sixteen-year experience with 1,000 heart transplants at UCLA.

1. The consecutive pre- and post-1994 eras have demonstrated improved survival for all age groups. This is linked to improved preservation methods, surgical technique and immunosuppression agents. 2. The use of marginal donor hearts for Status I and alternate elderly patients has followed the model of matching donor and recipient risk without affecting patient outcome and minimized the use of implantable assist devices. 3. A donor history of systemic gram-negative infection, hypertension, or traumatic intracranial bleeds was an important marker for risk. Younger age and shorter ischemia time could compensate for other hazards. 4. Heart transplantation in carefully selected elderly recipients yielded clinical results similar to those of younger patients with less rejection. 5. An adult alternate recipient list proved useful to prevent diversion of standard donors away from younger recipients. 6. Retransplantation for TCAD is acceptable but much less satisfactory for acute graft failure. 7. Trends show an increase in the use of implantable devices; refinement in technology for mechanical assist and replacement is forthcoming.

Adolescent↗
PubMed1999

Cloning of TACC1, an embryonically expressed, potentially transforming coiled coil containing gene, from the 8p11 breast cancer amplicon.

Amplification of several chromosomal regions have been observed in human breast carcinomas. One such region, 8p11, is amplified in 10-15% of tumor samples. Although the FGFR1 gene is located close to this region, and is often included within the amplicon, the observation that tumors exhibiting 8p11 amplification do not always overexpress FGFR1 suggests that another gene located close to FGFR1 is involved in the tumorigenic process. We now report the precise location of four expressed sequence tags (ESTs) within this region and the cloning of a novel gene, designated TACC1 (transforming acidic coiled coil gene 1), which encodes an 8 kb transcript and which is expressed at high levels during early embryogenesis. Constitutive expression of this gene under the control of the cytomegalovirus (CMV) promoter in mouse fibroblasts, results in cellular transformation and anchorage independent growth, suggesting that inappropriate expression can impart a proliferative advantage. This observation raises the possibility that amplification of TACC1 could promote malignant growth, thereby making TACC1 an attractive candidate for the gene promoting tumorigenicity as a result of the 8p11 amplification in human breast cancers.

Adult↗
PubMed1999

Mechanisms of IL-10 production in human microglia-T cell interaction.

IL-10, a cytokine with important anti-inflammatory properties, is generated within the CNS during neuroinflammation. The mechanism for its production is poorly understood. Since infiltrating lymphocytes come into close proximity with the macrophage-like cells of the CNS, the microglia, we have used an in vitro human microglia-T cell coculture system to address the mechanisms of IL-10 production. We demonstrate that microglia or activated T cells alone secrete negligible amounts of IL-10, but that their coculture results in significant IL-10 production, which was effected by both cell types. IL-10 generation was cell contact dependent, and treatment with anti-CD40, CTLA-4-Fc, or anti-CD23 decreased the IL-10 content in microglia-T cell cocultures. The combination of anti-CD40 and CTLA-4-Fc reduced IL-10 levels to the negligible amounts seen with T cells or microglia in isolation. By also measuring TNF-alpha levels, specificity of cytokine regulation was observed; while anti-CD40 and CTLA-4-Fc reduced IL-10 and TNF-alpha levels, anti-CD23 did not affect TNF-alpha while attenuating IL-10 generation. Anti-very late Ag-4, which decreased TNF-alpha levels, did not affect IL-10. These results implicate the CD40, B7, and CD23 pathways in IL-10 production following microglia-T cell encounter and have relevance to the regulation of an anti-inflammatory response within the CNS.

Abatacept↗
PubMed1999

Pharmacokinetics of thalidomide in an elderly prostate cancer population.

Thalidomide, a glutamic acid derivative, has recently been shown to inhibit in vitro angiogenesis, the process of formation of new blood vessels. This Phase II study examined the pharmacokinetics of thalidomide in patients with clinically progressive hormone-refractory prostate cancer. Patients (aged 55 to 80 years) were randomized to two different arms, low dose versus high dose. Patients in the low-dose group were given 200 mg of thalidomide and patients in the high-dose group received 200 mg of thalidomide, with subsequent dose escalations to 1200 mg. Serial serum or blood samples were obtained for pharmacokinetic assessment after administration of a single oral dose or multiple daily dosing of thalidomide and were assayed by reversed-phase HPLC. Pharmacokinetic parameters for both the single and multiple dosing were calculated with ADAPT II. A one-compartment model best fit the data. After single dosing, the oral clearance and apparent volume of distribution for the low-dose regimen (n = 13) were 7.41 +/- 2.05 L/h and 66.93 +/- 34.27 L, respectively, whereas for the high-dose regimen (n = 11), these values were 7.21 +/- 2.89 L/h and 165.81 +/- 84.18 L, respectively. The elimination half-lives for the low and high dose were 6.52 +/- 3.81 and 18.25 +/- 14.08 h, respectively. After the multiple dosing of thalidomide, the oral clearance and apparent volume of distribution for the low-dose group (n = 10) were 6.35 +/- 1.64 L/h and 64.63 +/- 23.20 L, respectively, whereas for the high-dose group (n = 11), these values were 7.73 +/- 2.27 L/h and 167.85 +/- 82.08 L, respectively. The elimination half-lives for the low and high dose were 7.08 +/- 1.87 and 16.19 +/- 9.57 h, respectively. For both the single and multiple dosing of thalidomide, the apparent volume of distribution and half-life were significantly higher for the high-dose group than those for the low-dose group. The higher apparent volume of distribution may be attributable to several factors, such as change in absorption, protein binding, etc. A dose-proportional increase in thalidomide steady-state concentrations was seen after multiple daily dosing of thalidomide.

Aged↗
PubMed1999

Distribution of uranium in rats implanted with depleted uranium pellets.

During the Persian Gulf War, soldiers were injured with depleted uranium (DU) fragments. To assess the potential health risks associated with chronic exposure to DU, Sprague Dawley rats were surgically implanted with DU pellets at 3 dose levels (low, medium and high). Biologically inert tantalum (Ta) pellets were used as controls. At 1 day and 6, 12, and 18 months after implantation, the rats were euthanized and tissue samples collected. Using kinetic phosphorimetry, uranium levels were measured. As early as 1 day after pellet implantation and at all subsequent sample times, the greatest concentrations of uranium were in the kidney and tibia. At all time points, uranium concentrations in kidney and bone (tibia and skull) were significantly greater in the high-dose rats than in the Ta-control group. By 18 months post-implantation, the uranium concentration in kidney and bone of low-dose animals was significantly different from that in the Ta controls. Significant concentrations of uranium were excreted in the urine throughout the 18 months of the study (224 +/- 32 ng U/ml urine in low-dose rats and 1010 +/- 87 ng U/ml urine in high-dose rats at 12 months). Many other tissues (muscle, spleen, liver, heart, lung, brain, lymph nodes, and testicles) contained significant concentrations of uranium in the implanted animals. From these results, we conclude that kidney and bone are the primary reservoirs for uranium redistributed from intramuscularly embedded fragments. The accumulations in brain, lymph nodes, and testicles suggest the potential for unanticipated physiological consequences of exposure to uranium through this route.

Animals↗
PubMed1999

The exercise-induced oxidative stress paradox: the effects of physical exercise training.

BACKGROUND: Although physical exercise training is highly recommended, physical exercise causes oxidative stress, which is potentially injurious. This study evaluates this 'exercise paradox' by evaluating the effect of physical exercise on exercise-induced lipid peroxidation. METHODS: Measurement of lipid peroxidation (ie, expired ethane and pentane and plasma malondealdehyde) taken during cardiopulmonary exercise stress testing were compared between a group of 10 cardiac patients who underwent physical exercise training in a cardiac rehabilitation setting and a group of 10 nonexercising cardiac patients. RESULTS: Our findings indicate that physical exercise training increased physical work capacity without a concomitant increase in expired markers of lipid peroxidation (ethane and pentane) and decreased malondealdehyde levels. CONCLUSIONS: Because physical exercise-trained people can perform more intense physical work with less oxidative stress, we conclude that physical exercise training can reduce potential chronic health effects associated with daily activities by contributing to an overall reduction in exercise-induced free radical production.

Adult↗
PubMed1999

Researching harm reduction--care and contradictions.

This paper sets out to identify why research is important in realizing the potential a harm-reduction framework has for informing policy and practice in relation to all psychoactive drugs. In doing so it includes examples of research about alcohol and tobacco, since legitimizing the harm-reduction approach requires strengthening the research foundation across both licit and illicit drugs. There are some practical as well as ethical and theoretical complexities in conducting research in this area, some of which are novel or exaggerated using harm-reduction principles. Potential impediments to research are identified. Articulation of these complexities might help to facilitate research which can help to determine the validity of harm reduction. The notion of the researchers "duty of care" might offer a way of deciding among competing accountabilities, but needs further articulation to be useful. [Translations are provided in the International Abstracts Section of this issue.]

Alcoholism↗
PubMed1999

Which glioblastoma multiforme patient will become a long-term survivor? A population-based study.

In this clinical and histopathological study, the frequency of long-term glioblastoma multiforme (GBM) survivors (LTGBMSs) was determined in a population-based study. The Alberta Cancer Registry was used to identify all patients diagnosed with GBM in Alberta between January 1, 1975, and December 31, 1991. Patient charts were reviewed and histology reexamined. LTGBMSs were defined as GBM patients surviving 3 years after diagnosis. Each LTGBMS was compared with 3 age-, sex-, and year of diagnosis-matched controls, and patient/treatment or tumor characteristics that predicted long-term survival were determined. There were 689 GBMs diagnosed in the study period; 15 (2.2%) of these patients survived 3 years. LTGBMSs (average age, 43.5 +/- 3.3 years) were significantly younger when compared with all GBM patients (average age, 53.0 +/- 0.56 years). LTGBMSs had a higher Karnofsky Performance Status score at diagnosis compared with controls. LTGBMSs were much more likely to have had a gross total resection and adjuvant chemotherapy than control GBM patients. Tumors from LTGBMSs tended to have fewer mitoses and a significantly lower Ki-67 cellular proliferation index compared with controls. Radiation-induced dementia was common and disabling in LTG-BMSs. In conclusion, conventionally treated GBM patients in an unselected population have a very small chance of long-term survival. The use of aggressive surgical resection and adjuvant chemotherapy may make long-term survival more likely in GBM patients if their performance status is high at diagnosis.

Adolescent↗
PubMed1998

A method of basal forebrain anatomical standardization for functional image analysis.

Functional as well as structural assessment of the basal forebrain has mostly focused on the dorsal caudate and putamen in axial slices where they are easily outlined or their centers located with stereotaxic methods. The more ventral extent of the basal forebrain, where the irregular form and indistinct boundaries of the nucleus accumbens and substantia innominata are difficult to trace and where the brain's ventral surface may contribute partial volume artifacts to measurement, has been less studied. We present a method based on coronal sections, landmarks placed on clearly visible anchor points, and the computational technique of thin-plate spline warping which allows the alignment of groups of individuals to common coordinates for pixel-by-pixel statistical mapping. The reliability of the landmarks across independent raters yields a median absolute difference of 1.3-1.6 mm. The validity of the method is confirmed by variance maps which reveal significant decreases in variance over spindle and bounding box alignment.

Adult↗
PubMed1998

Oncogenic Ha-Ras-dependent mitogen-activated protein kinase activity requires signaling through the epidermal growth factor receptor.

C3H10T1/2 fibroblasts transformed by the minimal expression of oncogenic Ha-Ras (V12H10 cells) or N-Ras (K61N10 cells) have constitutive mitogen-activated protein kinase (MAPK) activity and proliferate in serum-free medium. The constitutive MAPK activity and serum-independent proliferation of V12H10 cells are sensitive to the growth factor antagonist, suramin (Hamilton, M., and Wolfman, A. (1998) Oncogene 16, 1417-1428), suggesting that Ha-Ras-mediated regulation of the MAPK cascade is dependent upon the action of an autocrine factor. Serum-free medium conditioned by V12H10 cells contains an activity that stimulates MAPK activity in quiescent fibroblasts. This MAPK stimulatory activity could be specifically blocked by the epidermal growth factor receptor (EGFR) inhibitors, PD153035 and PD158780. These inhibitors also blocked the serum-independent proliferation of V12H10 cells. Immunodepletion of conditioned medium with antibodies to transforming growth factor alpha and EGF significantly inhibited its ability to stimulate MAPK activity. Stable transfection of EGFR-negative NR6 and EGFR-positive Swiss3T3 cells with oncogenic (G12V)Ha-Ras demonstrated that only the Ha-Ras-transfected Swiss 3T3 cells possessed constitutive MAPK activity, and this activity was sensitive to PD153035. These data suggest that autocrine activation of the EGFR is required for the regulation of the MAPK cascade in cells minimally expressing oncogenic Ha-Ras.

Animals↗