Search PubMed⌕ Search

Biomedical subjects

T Corbett

Publications and source records attributed to T Corbett.

At least 19 recordsLinked to original sources
PubMed2005

Do u smoke after txt? Results of a randomised trial of smoking cessation using mobile phone text messaging.

OBJECTIVES: To determine the effectiveness of a mobile phone text messaging smoking cessation programme. DESIGN: Randomised controlled trial SETTING: New Zealand PARTICIPANTS: 1705 smokers from throughout New Zealand who wanted to quit, were aged over 15 years, and owned a mobile phone were randomised to an intervention group that received regular, personalised text messages providing smoking cessation advice, support, and distraction, or to a control group. All participants received a free month of text messaging; starting for the intervention group on their quit day to assist with quitting, and starting for the control group at six months to encourage follow up. Follow up data were available for 1624 (95%) at six weeks and 1265 (74%) at six months. MAIN OUTCOME MEASURES: The main trial outcome was current non-smoking (that is, not smoking in the past week) six weeks after randomisation. Secondary outcomes included current non-smoking at 12 and 26 weeks. RESULTS: More participants had quit at six weeks in the intervention compared to the control group: 239 (28%) v 109 (13%), relative risk 2.20 (95% confidence interval 1.79 to 2.70), p < 0.0001. This treatment effect was consistent across subgroups defined by age, sex, income level, or geographic location (p homogeneity > 0.2). The relative risk estimates were similar in sensitivity analyses adjusting for missing data and salivary cotinine verification tests. Reported quit rates remained high at six months, but there was some uncertainty about between group differences because of incomplete follow up. CONCLUSIONS: This programme offers potential for a new way to help young smokers to quit, being affordable, personalised, age appropriate, and not location dependent. Future research should test these findings in different settings, and provide further assessment of long term quit rates.

Adolescent↗
PubMed2001

Predictors of breakthrough pain during labor epidural analgesia.

UNLABELLED: Parturients who receive labor epidural analgesia may experience breakthrough pain that requires supplemental medications. We investigated the factors associated with breakthrough pain. This prospective observational study included 1963 parturients who received epidural analgesia. Subjects were categorized into two groups on the basis of the number of episodes of breakthrough pain: the Recurrent Breakthrough Pain (RBP) group experienced three or more episodes. Univariate and multivariate regression analyses were used to evaluate factors associated with the RBP group. By multivariate analysis, nulliparity, heavier fetal weight, and epidural catheter placement at an earlier cervical dilation were found to be independently associated with the RBP group. These factors may predict which parturients' analgesia may be complicated by breakthrough pain. Parturients who received a combined spinal/epidural technique were less likely to be associated with the RBP group. The combined spinal/epidural technique may be superior to conventional epidural anesthesia, because breakthrough pain occurred less often. It is interesting to note that the characteristics that are associated with the RBP group are similar to those that have been associated with increased severity of maternal pain. IMPLICATIONS: Nulliparity, heavier fetal weight, and epidural catheter placement at an early cervical dilation are predictors of breakthrough pain during epidural labor analgesia. The combined spinal/epidural technique may be associated with a decreased incidence of breakthrough pain.

Adult↗
PubMed2000

A method for the preparation of highly purified adeno-associated virus using affinity column chromatography, protease digestion and solvent extraction.

Recombinant adeno-associated virus (AAV) is becoming the vector of choice for many gene therapy protocols. There has been much recent progress made toward increasing AAV titres but a continuing problem in using AAV has been that it is relatively difficult to concentrate and purify. Traditional methods, such as caesium chloride (CsCl) gradients, have drawbacks, notably extended purification times and the ability to process only limited volumes. Where the target cells of interest require a high multiplicity of infection (MOI), or to complete in vivo experiments, there is a requirement for both the production of high titre and a large volume of virus. This is laborious to obtain using traditional methods. A simple technique is described here for purifying AAV, involving affinity chromatography, protease digestion and solvent extraction that retains both the high yields and titres obtained using CsCl gradients. In addition, this technique displays a fast throughput and may be used to purify AAV from larger volumes than CsCl gradients. The high yield and purity of these virus preparations has allowed us to achieve good levels of expression in the target cell types tested. The purification technique described here will be applicable to any protocol that requires high titre, high purity recombinant AAV (rAAV).

Blotting, Western↗
PubMed1998

In vitro screening model for the detection of agents active against myelogenous leukemia.

This study was directed at defining the optimal in vitro screening methodology for the selection of new anti-myelogenous leukemia agents. Using thousands of samples of synthetic compounds from the Eastman Pharmaceutical, Inc. and Sterling Research Corporation (Eastman/Sterling) inventory, a number of sequential combinations of 8 cell lines were employed to optimize the model. The cells in these lines were of either murine (L1210 lymphocytic leukemia, C1498 myelogenous leukemia, and colony-forming unit-granulocyte macrophage [CFU-GM]) or human (HL-60, K-562, HEL, and THP-1 myelogenous leukemias, and CFU-GM) origin. The focus of the study was to find the most efficient and cost-effective manner in which to test compounds for both cytotoxicity against the tumor cells and for differential cytotoxicity against tumor as compared with normal cells.

Animals↗
PubMed1997

Construction and biological characterization of an interleukin-12 fusion protein (Flexi-12): delivery to acute myeloid leukemic blasts using adeno-associated virus.

Interleukin-12 (IL-12) is a cytokine that exhibits pleiotropic effects on lymphocytes and natural killer cells and has been shown to have promise for the immunotherapy of cancer. The combination of the immune costimulatory molecule B7.1 and IL-12 has been shown to be synergistic for T cell activation. By transfecting tumor cells with both IL-12 and B7.1 cDNAs, it may be possible to use these modified targets as vaccines. A major obstacle in designing a vector to deliver these genes results from the structure of IL-12. Functional IL-12 is a heterodimer composed of two distinct subunits that are encoded by separate genes on different chromosomes. Production of functional IL-12 requires the coordinated expression of both genes. This presents several problems in vectors, particularly those in which additional genes, either a co-stimulatory gene or a selectable marker, are inserted. Therefore, we have constructed a single cDNA that encodes a single-chain protein, called Flexi-12, which retains all of the biological characteristics of recombinant IL-12 (rIL-12). The monomeric polypeptide Flexi-12 is able to induce the proliferation of phytohemagglutinin (PHA) blasts, induce PHA blasts to secrete interferon-gamma (IFN-gamma) and additionally, by preincubation, enhance the killing of K562 targets by PBLs. These phenomena are in a dose-dependent manner comparable to that seen with rIL-12. We have also shown that tyrosine phosphorylation of the STAT 4 transcription factor, which has been shown to be unique to the IL-12 signaling pathway, occurs with Flexi-12 at levels similar to those seen with rIL-12. We have packaged Flexi-12 into a recombinant adeno-associated virus (AAV) and used this vector to infect acute myeloid leukemic (AML) blasts. Infected AML blasts produced between 2 and 6 ng of IL-12/10(6) cells per ml per 48 hr. These studies also confirm that AAV is an efficient delivery vehicle for cytokines to leukemic cells. Direct analysis of these modified cells acting as tumor vaccines is underway.

Amino Acid Sequence↗
PubMed1997

The in vitro detection of anti-leukaemia-specific cytotoxicity after autologous bone marrow transplantation for acute leukaemia.

Anti-leukaemia activity after allogeneic bone marrow transplantation has been studied extensively but its antigen specificity and effector cell phenotype remain unknown. Here we report a study in three recipients of autologous bone marrow transplantation done as part of the treatment for acute leukaemia, in whom we were able to detect innate specific anti-leukaemia activity post-transplant. One patient maintained selective cell-mediated cytolytic activity against her autologous leukaemic cells in the absence of cytolysis of her normal bone marrow mononuclear cells (BMMC). She remains in complete remission 3 years after ABMT for acute myeloid leukaemia (M5). A second patient was transplanted for acute lymphoblastic leukaemia and had detectable anti-leukaemia activity up to 20 weeks post-ABMT. At this point anti-leukaemia activity could no longer be demonstrated and the patient suffered a relapse 2 weeks later. A third patient was transplanted for AML (M4 Eo) and lacked detectable leukaemia-specific immune reactivity at 1, 3 and 6 months post-ABMT. She relapsed 6 months after her ABMT and returned to complete remission after further chemotherapy. She commenced treatment with alpha interferon and regained NK function. Furthermore, she developed high level cytolytic activity against her autologous leukaemic cells in the absence of activity against her remission bone marrow samples. She remains in complete remission 17 months after her initial relapse. This is the first report of an apparent association between in vitro leukaemia-specific cytolytic activity in individual patients after ABMT and clinical outcome. It encourages the theory that autologous immunomodulation may be useful in the future treatment of leukaemia.

Acute Disease↗
PubMed1996

Identification and antitumor activity of a reduction product in the murine metabolism of pyrazoloacridine (NSC-366140).

PURPOSE: Pyrazoloacridine (PZA) is a newly developed anticancer agent currently undergoing clinical trials. Its mode of action has not been elucidated but the presence in its chemical structure of a 5-nitro functional group and its activity against oxygen-deficient cancerous cells argue in favor of enzymatic nitro reduction as a possible pathway for its antitumor activity. In order to assess the involvement of the nitro functionality in PZA activity, as well as to determine other metabolic products, a pharmacological and chemical study of PZA was designed. METHODS: Urine and stool samples were collected from mice before and after treatment with PZA. Samples were fractionated using chromatographic methods and then evaluated using mass spectrometry (MS). One of the characterized metabolites was synthesized and tested in vitro and in vivo for anticancer activity. RESULTS: One major fraction from mouse stool was initially characterized by MS as the 5-aminopyrazoloacridine (5-APZ). This compound was chemically synthesized by catalytic hydrogenation of PZA was stabilized as the hydrochloride salt. 5-APZ was marginally cytotoxic in vitro and was inactive in vivo against a tumor cured by PZA (Panc 03). CONCLUSIONS: Bioreduction of the nitro group to an amine compound from PZA represents a pathway in the metabolic sequence of PZA. The inactivity of the chemically generated amine product does not provide conclusive evidence that this pathway is not involved in the cytotoxicity of PZA because other intermediates in the nitro reduction pathway may have a role in the activity of PZA. In particular, the hydroxylamine derivative of PZA could give answers to the involvement of this pathway in PZA cytotoxicity.

Acridines↗
PubMed1996

Formulation and antitumor activity evaluation of nanocrystalline suspensions of poorly soluble anticancer drugs.

PURPOSE: Determine if wet milling technology could be used to formulate water insoluble antitumor agents as stabilized nanocrystalline drug suspensions that retain biological effectiveness following intravenous injection. METHODS: The versatility of the approach is demonstrated by evaluation of four poorly water soluble chemotherapeutic agents that exhibit diverse chemistries and mechanisms of action. The compounds selected were: piposulfan (alkylating agent), etoposide (topoisomerase II inhibitor), camptothecin (topoisomerase I inhibitor) and paclitaxel (antimitotic agent). The agents were wet milled as a 2% w/v solids suspension containing 1% w/v surfactant stabilizer using a low energy ball mill. The size, physical stability and efficacy of the nanocrystalline suspensions were evaluated. RESULTS: The data show the feasibility of formulating poorly water soluble anticancer agents as physically stable aqueous nanocrystalline suspensions. The suspensions are physically stable and efficacious following intravenous injection. CONCLUSIONS: Wet milling technology is a feasible approach for formulating poorly water soluble chemotherapeutic agents that may offer a number of advantages over a more classical approach.

Animals↗
PubMed1992

Difluorodeoxycytidine (dFdC)--gemcitabine: a phase I study.

Difluorodeoxycytidine (dFdC) demonstrated broad spectrum activity in preclinical models. A phase 1 study utilizing twice weekly injections was conducted in 50 eligible and evaluable patients. Twenty-nine patients received drug by 30 minute infusion at doses of 5-90 mg/m2 and 22, by 5 minute bolus at 30-150 mg/m2. The primary dose limiting toxicities were marrow suppression and flu-like symptomatology. Thrombocytopenia was dose limiting at 75 mg/m2 on the infusion schedule and 150 mg/m2 on the 5 minute schedule. Flu-like symptoms with fever, rigors and malaise occurred the day of injection in many patients. One patient with renal cell carcinoma attained a partial response. Evaluation of the drug's efficacy and schedule dependency continue.

Adult↗
PubMed1991

Evidence for a contribution of paramagnetic ions to water proton spin-lattice relaxation in normal and malignant mouse tissues.

Paramagnetic ions complexed to proteins may lose, retain, or enhance solvent paramagnetic relaxation (SPR) relative to free solution. We measured T1 and T2 of three mouse cancers, their normal counterparts, and six additional tissues. Long T1 of cancers was not caused by necrosis or by different contents of water, fat, or blood. Dissociable (TCA-extractable) and nondissociable (ashed) Mn, Cu, and Fe were measured by AA. Cancers had less Mn, Cu, and Fe than did normal counterparts. All 12 tissues had inverse correlations between T1 and dissociable Mn and Cu. For Mn alone to account for reduced T1, the extent to which SPR of the Mn-protein complexes would be enhanced is by factors of 0.6 to 13, below the maximum observed in Mn-enzymes. Different amounts of paramagnetic ion-protein complexes may account for part of the differences in T1 of water protons in different tissues, and the longer T1 of cancer cell water may be caused in part by reduced amounts of such complexes.

Animals↗
PubMed1990

Discrepancy between cytotoxicity and DNA interstrand crosslinking of carboplatin and cisplatin in vivo.

We used the method of alkaline elution to compare quantitatively the DNA lesions produced by cisplatin and carboplatin in the AKR leukemia in vivo. These data were compared with cytotoxicity of each drug in the same animal model and in a solid tumor murine model (colon 26). DNA-protein and DNA-DNA interstrand crosslinks were formed in similar proportions by both drugs when peak values of crosslinking were compared. No clear difference in the rate of formation of both types of crosslinks could be observed between these drugs. On a molar basis a 3- to 4-fold more carboplatin had to be given to obtain equivalent frequencies of both types of crosslinks. In contrast, to obtain equitoxicity in the same animal tumor model, 13 fold higher doses of carboplatin had to be given. This difference in cytotoxicity between both drugs is comparable to the difference measured in colon 26 in vivo (16 fold). Both values are in the range of literature data (10-25 fold) dealing with the relative potency of cisplatin and carboplatin in murine tumor models.

Animals↗
PubMed1990

Flavone acetic acid and plasma protein binding.

Both the capacity of healthy human, cancer patient, and mouse plasma proteins to bind flavone acetic acid (FAA) and the qualitative differences in the plasma protein-binding site were studied. The binding capacity of plasma proteins for FAA was saturated within the therapeutic range in both species. The binding of FAA to plasma protein was significantly greater in both healthy human and cancer patient plasma than in mouse plasma. Plasma from patients with cancer bound on the average less FAA than did healthy patient plasma. The concentration of albumin in the plasma varied between healthy humans, cancer patients, and mice, being 5.3 +/- 0.7, 4.7 +/- 0.8, and 3.9 +/- 0.3 g/100 ml, respectively. The protein binding of FAA was found to be dependent on the plasma albumin concentration, but albumin concentration alone was not adequate for the accurate prediction of the percentage of FAA protein bound. Scatchard plots indicated that healthy human plasma had a greater number of high-affinity binding sites than did mouse plasma. FAA binds at the indolebenzodiazepine binding area on albumin and can be displaced from this site by salicylic acid and clofibric acid, but only at supratherapeutic concentrations. Our results indicate that alterations in plasma albumin could contribute to a variable effect with FAA. Therefore, the influence of serum albumin concentration and the nonlinearity of FAA protein binding should be considered in assessment of the appropriateness of a dose schedule for FAA.

Animals↗
PubMed1990

Interaction between flavone acetic acid (LM-975, NSC 349512) and radiation in Glasgow's osteogenic sarcoma in vivo.

Flavone acetic acid (FAA) is a new anticancer agent in Phase II trials in Europe. In preclinical testing FAA showed broad activity against murine solid tumors and minimal activity against murine leukemias. Our interest in studying the combination of FAA and radiation was based on two of its biological effects which might modify radiation damage. First, FAA depletes ATP and inhibits macromolecular synthesis which are needed to repair radiation-induced DNA strand breaks; and second, inhibition of tumor blood flow by FAA could lead to radiobiological hypoxia. Various schedules of FAA (170 mg/kg I.V.) (n = 9, SF = 0.44) and radiation (10 Gy) (n = 9, SF = 0.37) were investigated against s.c. implanted Glasgow osteogenic sarcoma. In the same model we studied both the kinetics of ATP depletion by 31P-Nuclear Magnetic Resonance Spectroscopy and the repair of radiation induced single and double strand breaks by alkaline elution. The combined response was not significantly different from log-additive when radiation was given 24, 5 or 1 hr before FAA. When FAA was given immediately before radiation an increase in tumor response, significantly different from log-additive (p = 0.03) was observed. This enhancement disappeared when radiation was delayed for between 1 and 48 hr after FAA. While decreased ATP levels and increased response to radiation occurred within minutes after FAA administration, no effect of FAA at either 180 or 200 mg/kg was observed on the repair of radiation induced single or double strand breaks (10 and 50 Gy, respectively; 5 hr after FAA) in spite of significant ATP depletion in the tumors.

Adenosine Triphosphate↗
PubMed1989

Early third trimester selective feticide of a compromising twin.

We report successful selective feticide of an anomalous, comprising twin by using intracardiac potassium chloride injection at 26 weeks gestation. This was associated with later delivery and survival of a very low birth weight infant with normal neurodevelopmental follow-up at 2 years. We suggest that selective feticide in such cases may have an important role to play in management.

Abnormalities, Multiple↗
PubMed1988

Flow cytometric DNA analysis of colon adenocarcinomas: a comparative study of preparatory techniques.

DNA quantitation of solid tumors requires either nuclear extraction or disaggregation into single cells for flow cytometric (FCM) analysis. We investigated methods for disaggregating colon carcinomas comparing mechanical and enzymatic techniques in fresh tumors and compared these to extraction of nuclei from paraffin blocks. Mechanical dissociation resulted in the highest yield of tumor cells, especially tumor cells with abnormal DNA content. In addition, mechanically disaggregated intact cells, particularly when dual labeled with cytokeratin, produced optimum DNA histograms. Cytokeratin staining allowed gating on epithelial cell populations and excluded contaminating diploid inflammatory and stromal cells, improving our ability to calculate synthesis phase fractions (SpF). Human colon tumor nuclei extracted from paraffin-embedded tissue resulted in greater variation of DNA histograms and less sensitivity in identifying aneuploid cells compared to mechanically dissociated intact cells from fresh tumors. The quality of the histograms and the ability to identify aneuploid cell populations were improved by modifying the standard "Hedley" technique by additional enzyme incubation. Mechanical dissociation of fresh tumors was the preferred technique for FCM DNA analysis. Nuclear extraction from paraffin blocks resulted in some loss of sensitivity in identifying aneuploid cell lines and decreased ability to measure SpF.

Adenocarcinoma↗
PubMed1987

A-ring substituted estrogens as inhibitors of the MXT transplantable mammary ductal carcinoma.

A-ring substituted estrogens have been examined as growth inhibitors of the hormone dependent MXT murine mammary tumor. Certain of these estrogen analogues inhibited the growth of newly implanted as well as established MXT tumors when administered either by s.c. or i.p. injections or by intubation. These compounds were nontoxic over a broad range of active levels. Amino and nitro groups, introduced at position-4 of estrone 3-methyl ether were particularly carcinostatic, a property not shared by 4-bromoestrone 3-methyl ether. In addition tumor inhibition was greatly diminished by placing the nitro group at the other ortho position (i.e., carbon-2). Evidence indicates that the A-ring substituted estrogens may function as growth inhibitors via the estrogen receptor mechanism in the case of 4-nitro- and 4-aminoestrone. The 3-methyl ethers of these compounds also blocked tumor growth, possibly through in vivo dealkylation leading to the free phenolic A-ring substituted estrogens. On the other hand, A-ring substituted 3-deoxyestrogens (particularly 4-nitro- and 4-aminoestratrien-17 beta-ol), which do not bind to receptor, were also excellent inhibitors of hormone dependent MXT breast tumors and therefore must express their activity by mechanisms other than that mediated by receptor. The A-ring substituted estrogens are unlike tamoxifen and diethylstilbestrol which (a) display toxicity at optimum inhibitory doses and (b) are inactive or marginally active in rodent breast cancer models.

Animals↗