Search PubMed⌕ Search

Biomedical subjects

M Todd

Publications and source records attributed to M Todd.

At least 19 recordsLinked to original sources
PubMed2001

Enoxaparin and abciximab adjunctive pharmacotherapy during percutaneous coronary intervention.

Randomized controlled trials of patients with non-ST segment elevation acute coronary syndromes have established the superiority of enoxaparin (versus unfractionated heparin) for reducing adverse ischemic outcomes. Furthermore, adjunctive abciximab therapy during percutaneous coronary intervention (PCI) is associated with improved clinical outcomes. Since algorithms for integrating these pharmacotherapies have not been determined, patients undergoing elective PCI were enrolled into 2 distinct and separate studies conducted by the National Investigators Collaborating on Enoxaparin (NICE) study groups (NICE 1 and NICE 4 studies). Patients in NICE 1 were administered enoxaparin 1.0 mg/kg intravenously (without abciximab) and those enrolled in NICE 4 were administered a reduced dose (0.75 mg/kg) of enoxaparin in combination with standard-dose abciximab intravenously during PCI. Bleeding events and ischemic outcomes assessed in-hospital and at 30-days post-PCI were infrequent with either pharmacologic regimen. In the dose regimens studied, enoxaparin with or without abciximab appears to provide safe and effective anticoagulation during PCI. The combination of reduced-dose enoxaparin and abciximab was associated with a low incidence of adverse outcomes (bleeding or ischemic events). Additional studies may be required to establish the relative safety and efficacy of this new adjunctive pharmacologic strategy when compared with the combination of low-dose, weight-adjusted unfractionated heparin and abciximab.

Abciximab↗
PubMed1999

A longitudinal study of children of alcoholics: predicting young adult substance use disorders, anxiety, and depression.

This study tested the specificity of parent alcoholism effects on young adult alcohol and drug abuse/dependence, anxiety, and depression, and tested whether adolescent symptomatology and substance use mediated parent alcoholism effects. Participants were from a longitudinal study in which a target child was assessed in adolescence and young adulthood with structured interview measures (N = 454 families at Time 1). Results showed unique effects of parent alcoholism on young adult substance abuse/dependence diagnoses over and above the effects of other parental psychopathology. There was some evidence of parent alcoholism effects on young adult depression and of maternal alcoholism effects on young adult anxiety, although these were not found consistently across subsamples. Mediational models suggested that parent alcoholism effects could be partially (but not totally) explained by adolescent externalizing symptoms.

Adolescent↗
PubMed1999

Isolation and characterisation of a prenylated p-terphenyl metabolite of Aspergillus candidus possessing potent and selective cytotoxic activity; studies on mechanism of action.

We describe the discovery and properties of a prenylated p-terphenyl metabolite of the fungus Aspergillus candidus. The compound (1) possesses potent cytotoxic activity against a range of tumour and other hyper-proliferative cell lines. Cell cycle analysis shows that in mouse keratinocyte (BALB/MK) cells treated with 1, the cell cycle is arrested in early S phase, indicative of an antimetabolite effect. Furthermore, cellular cytotoxicity can be reversed by addition of exogenous pyrimidine but not purine nucleosides to the cell culture medium. It is therefore likely that compound 1 selectively inhibits pyrimidine biosynthesis, and it is this property which accounts for its potent cytotoxic properties.

Animals↗
PubMed1998

Maternal socialization of adolescent smoking: the intergenerational transmission of parenting and smoking.

A longitudinal multigenerational design was used to examine the intergenerational transmission of smoking and the correlated transmission of parental support and control. Whether maternal socialization of adolescent smoking (both general parenting practices and smoking-specific strategies) would predict adolescent smoking both directly and indirectly by affecting peer affiliations was tested. There was strong evidence for the intergenerational transmission of cigarette smoking and for the relation between peer smoking and adolescent smoking. Both general parenting practices and smoking-specific discussion and punishment were significantly related to adolescents' smoking, especially for adolescent-reported parenting. Support for the intergenerational transmission of parenting practices emerged only in mothers' reports of support. Results suggest expanding current peer-focused prevention efforts to include parental socialization strategies.

Adolescent↗
PubMed1998

People with learning disabilities who also have mental health problems: practice issues and directions for learning disability nursing.

The plight of people with learning disabilities who have mental health problems has become an issue of contemporary importance in the provision of health services to this section of the population. This paper will argue that learning disability nursing has a central role to play in the promotion of mental health for this client group (Department of Health 1995a). However, learning disability nursing presently operates without a clear model of mental health. Therefore, before this potential can be realized there is a need to establish the common ground between the discourses of learning disability nursing and those of psychiatric nursing which might be related to this client group. This paper begins by identifying the background issues relating to the problems of meeting the mental health needs of people with learning disabilities. It then proposes that an applied behavioural approach has the potential to provide a coherent theory that can link the discourses of normalization, developmental psychiatry and mental health nursing, whilst also establishing the applied behavioural approach as a powerful technology upon which meaningful interventions can be designed.

Behavior Therapy↗
PubMed1998

The differences in electroencephalographic changes in patients undergoing carotid endarterectomies while under local versus general anesthesia.

OBJECTIVE: This study compared the electroencephalographic (EEG) changes occurring during carotid occlusion in 225 consecutive patients undergoing carotid endarterectomies performed by two surgeons, one using local and the other using general anesthesia. METHODS: A retrospective review of patients undergoing carotid endarterectomies for carotid occlusive disease was conducted. EEG changes associated with intraoperative ischemia (decreased amplitude, generalized slowing, and loss of fast activity) resulting in the need for an indwelling arterial shunt were recorded for the two anesthesia groups. To determine the similarities or differences between the two groups, the groups were compared regarding age, risk factors, and indications for surgery. RESULTS: Significant EEG changes were noted in 6 of 96 patients (6.3%) in the local anesthesia group versus 19 of 121 patients (15.7%) in the general anesthesia group. EEG changes consisted solely of generalized slowing in the local anesthesia group, whereas a more varied spectrum was observed in the general anesthesia group. The two groups were similar regarding age and risk factors. Although the local anesthesia group had more asymptomatic patients, symptomatic patients did not have a greater incidence of EEG changes. CONCLUSION: There is a large difference in EEG changes potentially requiring shunt placement in patients undergoing surgery while under local (6.3%) versus general (15.7%) anesthesia. This could not be explained based on age, risk factors, interpretation of EEG findings, or indications between the two groups. We conclude that EEG monitoring may be insensitive and may fail to detect ischemia in patients who are under regional anesthesia. Alternately, the presence of general anesthetics may alter the character of the EEG findings and increase the sensitivity of EEG monitoring to ischemic events.

Anesthesia, General↗
PubMed1997

A mutation in the methylenetetrahydrofolate reductase gene is not associated with increased risk for coronary artery disease or myocardial infarction.

OBJECTIVES: We sought to determine whether the C677T transition in the methylenetetrahydrofolate reductase (MTHFR) gene is associated with increased risk for coronary artery disease (CAD) or myocardial infarction (MI). BACKGROUND: Elevated plasma homocysteine has been identified as a risk factor for coronary atherosclerosis. Homocysteinemia may result from deficient MTHFR activity. A thermolabile form of MTHFR, associated with a C677T genetic transition, shows reduced activity and may be a risk factor for CAD. METHODS: Blood was withdrawn from patients undergoing coronary angiography, and DNA was extracted by a phenol-chloroform method. Genotyping was done by polymerase chain reaction (PCR) amplification of a 198-base pair segment of the MTHFR gene that brackets nucleotide 677. The amplicon was digested with the HinfI restriction enzyme. Products were visualized after electrophoresis in 1.5% agarose with ethidium bromide. RESULTS: Among 200 patients with a diagnosis of MI, the polymorphic allelic frequency was 33.3%, compared with 32.1% among 554 control subjects (p = 0.68); homozygosity was present in 11.5% of patients and 10.6% of control subjects (p = 0.74, odds ratio [OR] 1.09, 95% confidence interval [CI] 0.63 to 1.82). Among 510 patients with severe CAD (>60% stenosis), allelic frequency was 32.0%, compared with 34.8% for 168 subjects without CAD (<10% stenosis, p = 0.33); 11.2% of patients with CAD compared with 13.1% of control subjects were homozygous (p = 0.50, OR 0.83, 95% CI 0.5 to 1.40). CONCLUSIONS: Patients with angiographic evidence of CAD or clinical MI do not show an increased frequency of the C677T transition in the MTHFR gene. Our findings do not support this polymorphism as a risk factor for CAD or MI in a predominantly white, well nourished population of unrestricted age.

Adult↗
PubMed1997

An efficient process for production of N-acetylneuraminic acid using N-acetylneuraminic acid aldolase.

N-acetyl-D-neuraminic acid (Neu5Ac) aldolase (EC 4.1.3.3) has bee reported for synthesis of Neu5Ac,1-5 but there are no reports of processes which do not have significant drawbacks for large-scale operation. Here, Neu5Ac aldolase from an overexpressing recombinant strain of Escherichia coli has been used to develop an immobilized enzyme process for production of Neu5Ac. The enzyme was immobilized onto Eupergit-C and could be reused many times in the reaction. Base-catalyzed epimerization of N-acetyl-D-glucosamine (GlcNAc) yielded GlcNAc/N-acetyl-D-mannosamine (ManNAc) mixtures (c 4:1) which could be used directly in the aldolase reaction; however, inhibition of the enzyme by GlcNAc limited the concentration of ManNAc which could be used in the reaction by this approach. This necessitated the addition of a large molar excess of pyruvate (five- to seven-fold) to drive the equilibrium over to Neu5Ac; nevertheless, a method has been developed to remove the excess pyruvate effectively by complexation with bisulfite, thus allowing Neu5Ac to be recovered by absorption onto an anion-exchange resin. In a second approach, a method has been developed to enrich GlcNAc/ManNAc mixtures for ManNAc. ManNAc can be used at high concentrations in the reaction, thus obviating the need to use a large molar excess of pyruvate. Neu5Ac can be isolated from such reaction mixtures by a simple crystallization. This work shows the importance of integrated process solutions for the effective scale-up of biotransformation reactions.

1-Propanol↗
PubMed1996

Recombinant beta-interferon in the treatment of patients with metastatic renal cell carcinoma.

We report on the clinical course of 15 patients with metastatic renal cell carcinoma (RCC) who were treated with recombinant beta-interferon as part of a phase I-II study. There were no objective responders among the 15 patients treated with recombinant beta-interferon at an i.v. dose escalating from 90 X 10(6) U given three times a week until there was documented disease progression or complete response (CR). Overall median survival was 24 months. One patient refused further treatment after 7 weeks. The major side effects of treatment included cardiovascular events (20%), mental status change requiring cessation of drug (6.7%), and grade 3 headaches/myalgias (26.7%). There were no life-threatening side effects observed; however, cardiac events led to the termination of treatment in three patients. Other minor toxicities included fatigue (46.7%), proteinuria (60%), diarrhea (6.7%), nausea and vomiting (13.3%), persistent fever (6.7%) and transient visual disturbance (6.7%). Thus, at our institution, in a cohort of 15 patients with metastatic RCC, recombinant beta-interferon when given i.V. at a dose < or equal to 720 X 10(6) U three times per week, yielded no clinical antitumor activity. A review of the literature on the use of beta-interferon for metastatic RCC suggests that there may be some efficacy, but our experience with escalating i.v. doses < or equal to 720 X 10(6) U given three times a week does not support it. Moreover, at these doses, one may find serious cardiovascular events although further studies need to be done in order to clearly define dose-related side effects as well as optimal efficacy-to-toxicity ratio.

Aged↗
PubMed1996

Magnetizable solid-phase supports for purification of nucleic acids.

A simple, small scale non-hazardous procedure for the production of magnetizable solid-phase support (MSPS) beads has been developed based on the extrusion of agarose/iron oxide mixtures. The MSPS beads were derivatized using various amine ligands. Derivatized MSPS beads were used to adsorb nucleic acids from aqueous solution and to separate RNA/DNA mixtures.

Chromatography, Agarose↗
PubMed1995

Biochemical modulation of 5-fluorouracil with brequinar: results of a phase I study.

Biochemical modulation can increase the efficacy of 5-fluorouracil (5-FU). Pizzorno et al. have previously shown that brequinar, a de novo pyrimidine synthesis inhibitor, enhances the antitumor effect of 5-FU in vivo [Cancer Res 52: 1660-1665, 1992]. On the basis of their data, we conducted a phase I study of brequinar in combination with 5-FU in patients with refractory solid tumors. The initial dose (100 mg/m2) of brequinar was raised in 100-mg/m2 increments in cohorts of three assessable patients. The initial dose of 5-FU was 500 mg/m2, but escalation was allowed in patients who showed no significant toxic reaction. Brequinar was administered over 1 h and 5-FU over 2 h starting 18-20 h after the initiation of infusion of brequinar. Treatments were repeated weekly. Responses were evaluated after 4 weeks (one course) and then every 8 weeks thereafter. Pharmacokinetics of brequinar and determination of plasma uridine levels were performed in at least three patients at each dose level. Of the 25 patients registered in the study, 21 were assessable for toxicity studies. The dose of brequinar was escalated up to 600 mg/m2. In addition, the dose of 5-FU was increased to 600 mg/m2 as a result of a lack of a significant toxic reaction in the first nine patients. No objective responses were observed. One patient developed grade 3 stomatitis, and one developed grade 3 esophagitis at the 400 and 600 mg/m2 dose of brequinar, respectively. Brequinar produced a dose-dependent decrease in plasma uridine levels at doses up to 500 mg/m2. No additional decrease in plasma uridine occurred with higher doses of brequinar, thus suggesting a plateau effect. This observation prompted us to terminate the study before reaching the maximum tolerated dose of brequinar. Our data indicate that brequinar in doses > or = 400 mg/m2 results in significant biochemical modulation. The lack of toxicity seen at these doses of brequinar suggests that the initial dose of the effector agent 5-FU should be increased in future studies.

Adult↗
PubMed1995

Preventing intimal hyperplasia with photodynamic therapy using an intravascular probe.

The purpose of this study was to determine the efficacy of intravascular photodynamic therapy (PDT) to prevent the development of intimal hyperplasia. Anesthetized New Zealand white rabbits underwent placement of Fogarty balloon catheters introduced via femoral artery cutdowns. Catheters were passed retrograde 10 cm into the lower abdominal aorta, inflated six times, and withdrawn toward the inguinal ligament. Rabbits were then randomly assigned to one of the following groups: group 1, drug with no light; group 2, no drug with 240 joules of light; group 3, drug plus 120 joules of light; or group 4, drug plus 240 joules of light. Uninjured carotid arteries served as negative control vessels (N) and injured but non-PDT-treated iliac artery segments served as positive controls (P). Porfimer sodium (photofrin) was administered in a dose of 5.0 mg/kg. Light was provided by a fiberoptic probe with a 1 cm cylindric diffuser attached to an argon pumped dye laser tuned to 630 nm to provide 1 W of laser light for 120 or 240 seconds. One month after PDT, rabbits were killed, perfusion fixed with glutaraldehyde, and vessels removed and examined microscopically. Intimal thickness (mean +/- SD) was calculated and expressed as ratios of the intima/media at four equal positions. Results for N, P, and groups 1, 2, 3, and 4 were 0.02 +/- 0.00, 1.18 +/- 0.71, 0.76 +/- 0.33, 0.96 +/- 0.43, 0.14 +/- 0.22, and 0.36 +/- 0.16, respectively. Intimal thickness was significantly reduced in groups 3 and 4 when compared with P, group 1, and group 2 (p < 0.001, ANOVA). These results showed that intravascular PDT was effective in reducing intimal hyperplasia following arterial injury. This may be a practical method of delivering light for PDT.

Animals↗
PubMed1995

Novel squalestatins produced by biotransformation.

Microorganisms were screened for the ability to modify the squalene synthase inhibitor squalestatin 1. Biotransformation of 1 by two actinomycetes, S15106 and S15138, yielded three products hydroxylated on the 4,6-dimethyl-oct-2-enoyl side chain either at the 6 position (5) or 7 position (4 two diastereoisomers), and lacking the acetyl ester from the C-1 side chain. Many strains were found to hydrolyse the 4,6-dimethyl-oct-2-enoyl or acetyl esters to yield squalestatins 2 or 3. The 3-methyl ester (6) of 1 was obtained using Fusarium sp. F13945. This fungus also produced a farnesoic acid derivative, possibly in response to inhibition of its squalene synthase by 1. The biotransformation products of 1 all retained potent squalene synthase inhibitory activity.

Actinomycetales↗
PubMed1994

Polyethylene glycolated interleukin-2 as maintenance therapy for acute myelogenous leukemia in second remission.

Seven patients in second complete remission of acute myeloid leukemia (AML) aged 19-65 years were treated with polyethylene glycolated interleukin-2 (PEG IL-2), 1 x 10(6) U/M2 IV weekly as the sole postremission therapy. Second remission duration was in the range of 4-49+ months, and three patients had a second remission duration substantially longer than their first (6, 21+, and 42+ months). The results suggest that PEG IL-2 may prolong second remission duration in AML and that a prospective randomized study designed to test that idea is warranted.

Adult↗
PubMed1994

Preparation, characterization, and evaluation of a monoclonal antibody against the rabbit platelet glycoprotein IIb/IIIa in an experimental angioplasty model.

The deposition of platelets at the site of balloon angioplasty is thought to play a major role in the pathogenesis of restenosis. The antibody AZ-1, which binds to the rabbit platelet glycoprotein IIb/IIIa receptor and inhibits platelet function both in vitro and in vivo, was produced and tested in an experimental model of angioplasty. Atherosclerosis was induced by desiccation injury of the femoral artery, followed by a 28-day diet with 2% cholesterol and 6% peanut oil. Rabbits were randomized to receive an infusion of saline, a single infusion of 0.5 mg/kg of AZ-1, or an infusion of 0.6 mg/kg AZ-1 before angioplasty. The latter group received a second infusion of 0.6 mg/kg 72 hours later. Functional platelet inhibition was demonstrated by prolongation of the bleeding time in all treated animals. Angiography was performed at baseline, immediately after a standardized angioplasty, and again 28 days after angioplasty on a total of 42 vessels. There were no significant differences between the antibody-treated group and the control group in the mean angiographic minimum luminal diameter at any of the time points. There was also no difference in the initial improvement after angioplasty (acute gain), in the decrease in luminal diameter from immediately after angioplasty to 28 days after angioplasty (late loss), or in the overall improvement from before angioplasty to 28 days after angioplasty. Quantitative histological analysis confirmed the lack of a beneficial effect of AZ-1. There were no significant differences in the area of the intima, the media, or the combined intima and media between the antibody-treated groups and the control group. Thus, potent platelet inhibition for up to 6 days after balloon angioplasty using a monoclonal antibody that inhibits platelet aggregation did not reduce the response to vascular injury after balloon angioplasty in this rabbit model of experimental atherosclerosis.

Angioplasty↗
PubMed1994

Comparison of the efficacy of three dose levels of moexipril versus placebo as add-on therapy to hydrochlorothiazide in patients with moderate hypertension.

This parallel, double-blind trial was designed to evaluate the efficacy of three dose levels of moexipril versus placebo as add-on therapy to hydrochlorothiazide (HCTZ) in patients with uncomplicated moderate to severe hypertension. Two hundred patients (aged 25-74 years) with sitting diastolic blood pressure (DBP) between 95 and 114 mm Hg after 4 week treatment with HCTZ 25 mg once daily were randomized to placebo, or moexipril 3.75, 7.5 mg, or 15 mg. BP was measured at 22-26 h postdose at biweekly visits and at 1, 2, 3, and 4 h postdose after the first dose of double-blind medication. At endpoint, adjusted mean reductions from baseline sitting DBP were 8.4, 8.8, and 8.9 mm Hg in the moexipril 3.75-, 7.5-, and 15-mg groups, respectively, as compared with a reduction of 4.6 mm Hg in the placebo group (p = 0.003). The differences in systolic BP (SBP) reductions were statistically significant in favor of each of the moexipril groups over the placebo group at all trough time-points. Adjusted mean changes in sitting SBP were 10.9, 12.0, and 11.7 mm Hg, respectively, as compared with a reduction of 0.6 mm Hg in the placebo group (p < 0.001). Our results indicate that moexipril and HCTZ constitute a clinically valuable combination in treatment of patients with moderate to severe hypertension.

Adult↗
PubMed1993

Probing the effects of individual components in multiple component prevention programs.

Assessing the contributions of individual components in multi-component interventions poses complex challenges for prevention researchers. We review the strengths and weaknesses of designs and analyses that may be useful in answering three questions: (1) Is each of the individual components contributing to the outcome? (2) Is the program optimal? and (3), Through what processes are the components of the program achieving their effects? Factorial and fractional factorial designs in which a systematically selected portion of all possible treatment combinations is implemented are used to address question 1. Response surface designs in which each component is quantitatively scaled are explored in relation to question 2. Mediational analysis, a hybrid of experimental and correlational approaches, is considered in relation to question 3. Design enhancements are offered that may further strengthen some of these techniques. These techniques offer promise of enhancing both the basic science and applied science contributions of prevention research.

Combined Modality Therapy↗