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Biomedical subjects

Andrew Simpson

Publications and source records attributed to Andrew Simpson.

17 recordsLinked to original sources
PubMed2006

Adjuvant chemotherapy for non-small cell lung cancer: a New Zealand perspective.

This article reviews recent developments with the use of adjuvant chemotherapy for resected early-stage non-small cell lung cancer (NSCLC) and the implications of these developments for healthcare in New Zealand (NZ). Non-small cell lung cancer is a major cause of mortality and morbidity in NZ, and is greatly over-represented among Maori and socioeconomically deprived populations. Early-stage NSCLC is potentially curable by surgery, but long-term outcome after surgical resection is limited by disease recurrence locally or at sites distant from the primary disease. Three recent large randomised controlled phase III trials using modern platinum-based combination chemotherapy protocols have shown significant survival benefits for the use of postoperative adjuvant chemotherapy after resection of early-stage NSCLC. Cisplatin plus vinorelbine was used as the adjuvant chemotherapy regimen in two of these trials resulting in improvements in 5-year survival of 51.2% versus 42.6% (p=0.013) and 69% versus 54% (p=0.03), respectively. In NZ, adjuvant chemotherapy for NSCLC is expected to prevent up to 15 lung cancer deaths each year for relatively low drug expenditure and has the potential to benefit Maori and the economically-deprived disproportionately more than other populations. In conclusion, it is the opinion of this group of NZ lung cancer specialists that adjuvant chemotherapy with cisplatin plus vinorelbine should now be adopted as a standard of care for patients with resected stage II and III NSCLC. For this to occur, current PHARMAC policies preventing its use for these eligible patients will need to be revised.

Antineoplastic Agents, Phytogenic↗
PubMed2006

Changes in the capacity of visual working memory in 5- to 10-year-olds.

Using the Luck and Vogel change detection paradigm, we sought to investigate the capacity of visual working memory in 5-, 7-, and 10-year-olds. We found that performance on the task improved significantly with age and also obtained evidence that the capacity of visual working memory approximately doubles between 5 and 10 years of age, where it reaches adult levels of approximately three to four items.

Age Factors↗
PubMed2006

Is belief reasoning automatic?

Understanding the operating characteristics of theory of mind is essential for understanding how beliefs, desires, and other mental states are inferred, and for understanding the role such inferences could play in other cognitive processes. We present the first investigation of the automaticity of belief reasoning. In an incidental false-belief task, adult subjects responded more slowly to unexpected questions concerning another person's belief about an object's location than to questions concerning the object's real location. Results in other conditions showed that responses to belief questions were not necessarily slower than responses to reality questions, as subjects showed no difference in response times to belief and reality questions when they were instructed to track the person's beliefs about the object's location. The results suggest that adults do not ascribe beliefs to agents automatically.

Adult↗
PubMed2006

Designing for e-Health: recurring scenarios in developing grid-based medical imaging systems.

The paper draws on a number of Grid projects, particularly on the experience of NeuroGrid, a UK project in the Neurosciences tasked with developing a Grid-based collaborative research environment to support the sharing of digital images and patient data across multiple distributed sites. It outlines recurrent socio-technical issues, highlighting the challenges of scaling up technological networks in advance of the regulatory networks which normally regulate their use in practice.

Biomedical Research↗
PubMed2005

Conditions under which children experience inhibitory difficulty with a "button-press" go/no-go task.

Go/no-go tasks seem to provide a simple marker of inhibitory development in young children. Children are told to respond to one stimulus on go trials but to make no response to another stimulus on no-go trials; responding on no-go trials is assumed to reflect a failure to inhibit the go response. However, there is evidence to suggest that a type of go/no-go task, which we call the "button-press" task, does not require inhibition. We investigated the conditions under which young children (M=3 years 6 months, N=120) experience inhibitory difficulty with this type of task. The data suggest that the speed of stimulus presentation is crucial and that other studies using this type of task have presented the stimuli too briefly. The importance of establishing the inhibitory credentials of a task before it is used as a marker of inhibitory control is emphasized.

Analysis of Variance↗
PubMed2005

What's happening in PHARMAC--where do all the submissions go? On the trail of gemcitabine.

The process and progress of submissions to PHARMAC for funding of new treatments is unclear. There appears to be a lack of communication or transparency regarding funding applications, decisions, or expected timelines to reach an endpoint. It is difficult to have confidence in a process that lacks such definition. A recent clinician submission for funding of an oncology treatment (gemcitabine) for bladder cancer highlights these issues.

Antimetabolites, Antineoplastic↗
PubMed2005

Executive inhibition and semantic association in schizophrenia.

Research indicates that some patients with schizophrenia display aberrant inhibition of semantic memory, which may underpin formal thought disorder (FTD). We administered a novel Stroop-like paradigm to three groups of participants: 15 schizophrenic patients with formal thought disorder (FTD), 16 with low FTD ratings, and 15 healthy matched controls. They were required to inhibit a prepotent response for a (previously instructed) required response. Four conditions examined the effect of executive demands by manipulating the relatedness between prepotent and required responses (i.e., identical, semantically related, or unrelated). Two further conditions examining executive function working memory demands required the naming of real or abstract pictures that did and did not necessitate inhibition, respectively. Patients with and without FTD experienced increased difficulty when executive function working memory was required. Moreover, those with FTD also showed increased executive inhibition, but the pattern of errors suggested that the result of this was an automatic activation of semantically related representations. The findings support the notion that increased inhibition underpins the disorganised access to semantic memory in patients with FTD.

Association↗
PubMed2005

Effects of systemically administered NT-3 on sensory neuron loss and nestin expression following axotomy.

Previous work has shown that administration of the neurotrophin NT-3 intrathecally or to the proximal stump can prevent axotomy-induced sensory neuron loss and that NT-3 can stimulate sensory neuron differentiation in vitro. We have examined the effect of axotomy and systemic NT-3 administration on neuronal loss, apoptosis (defined by morphology and activated caspase-3 immunoreactivity), and nestin expression (a protein expressed by neuronal precursor cells) in dorsal root ganglia (DRG) following axotomy of the adult rat sciatic nerve. Systemic administration of 1.25 or 5 mg of NT-3 over 1 month had no effect on the incidence of apoptotic neurons but prevented the overall loss of neurons seen at 4 weeks in vehicle-treated animals. Nestin-immunoreactive neurons began to appear 2 weeks after sciatic transection in untreated animals and steadily increased in incidence over the next 6 weeks. NT-3 administration increased the number of nestin-immunoreactive neurons at 1 month by two- to threefold. Nestin-IR neurons had a mean diameter of 20.78 +/- 2.5 microm and expressed the neuronal markers neurofilament 200, betaIII-tubulin, protein gene product 9.5, growth associated protein 43, trkA, and calcitonin gene-related peptide. Our results suggest that the presence of nestin in DRG neurons after nerve injury is due to recent differentiation and that exogenous NT-3 may prevent neuron loss by stimulating this process, rather than preventing neuron death.

Animals↗
PubMed2005

Young children have difficulty ascribing true beliefs.

Using the format of a false belief task (Wimmer & Perner, 1983), we investigated the ability of 88 3- and 4-year-olds to ascribe a previously held true belief to a story protagonist. In an unexpected transfer task, children found true belief ascription as difficult as false belief ascription even though they could answer memory questions about story details. Results are discussed in relation to theoretical accounts of theory of mind development that stress the importance of understanding the falsity of belief, and those accounts that stress the importance of information or executive processes.

Chi-Square Distribution↗
PubMed2005

Factors responsible for performance on the day-night task: response set or semantics?

In a recent study Diamond, Kirkham and Amso (2002) obtained evidence consistent with the claim that the day-night task requires inhibition because the picture and its corresponding conflicting response are semantically related. In their study children responded more accurately in a dog-pig condition (see /day picture/ say "dog"; see /night picture/ say "pig") than the standard day-night condition (see /day picture/ say "night"; see /night picture/ say "day"). However, there is another effect that may have made the day-night condition harder than the dog-pig condition: the response set effect. In the day-night condition the names of the two stimuli ("day" and "night") and the two corresponding conflicting responses ("night" and "day") are from the same response set: both "day" and "night". In the dog-pig condition the names of the stimuli ("day", "night") and the corresponding responses ("dog", "pig") are from a different response set. In two experiments (Experiment 1 with 4-year-olds (n = 25); Experiment 2 with , 4-, 5-, 7- and 11-year-olds (n = 81)) children were tested on four experimental conditions that enabled the effects of semantics and response set to be separated. Overall, our data suggest that response set is a major factor in creating the inhibitory demands of the day-night task in children of all ages. Results are discussed in relation to other inhibitory tasks.

Age Factors↗
PubMed2004

Alcohol dehydrogenase 3 genotype as a risk factor for upper aerodigestive tract cancers.

OBJECTIVE: To assess alcohol dehydrogenase 3 (ADH3) polymorphism at position Ile349Val as indicator of risk factor for upper aerodigestive tract (UADT) cancer to verify its association with UADT cancer in nonalcoholic or nonsmoking individuals. DESIGN: Cross-sectional study. SETTING: Primary care or referral center. PATIENTS: The study group consisted of 141 consecutive patients with newly diagnosed squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx admitted for surgical treatment. The comparison group consisted of 94 inpatients without cancer from the A. C. Camargo or other São Paulo (Brazil) hospital and 40 healthy individuals. INTERVENTION: All participants were interviewed and data were collected using a structured questionnaire. After written informed consent was obtained, 20 mL of blood was collected in heparinized tubes. MAIN OUTCOME MEASURES: Odds ratio for ADH3 genotypes using logistic regression models. RESULTS: After adjustment for sex, age, tobacco use, and history of cancer in first-degree family relatives, a significantly higher odds ratio for UADT cancer was observed among individuals with AA genotype and low cumulative alcohol consumption (< or =100 kg of ethanol) (odds ratio = 3.8 [95% confidence interval, 1.5-9.7]). A 4-fold increase in odds ratio for UADT cancer among individuals with AA genotype and low tobacco consumption (< or =25 pack-years) was also found in the adjusted model. CONCLUSIONS: These results suggest that genotype AA may be a risk factor for UADT cancer, especially in individuals with low alcohol or tobacco consumption. However, further epidemiological case-control or cohort studies, preferably prospective, are needed to establish the exact role of ADH3 polymorphism and its association with the development of UADT cancers.

Adult↗
PubMed2004

What makes the windows task difficult for young children: rule inference or rule use?

The windows task is difficult for young children. In this task, a child is shown two boxes with windows revealing that one is empty, whereas the other contains a treat. The child is asked to point to a box for an opponent to look in. The child then "wins" the contents of the other box (the treat). To pass the task, the child must use a rule such as "point to the empty box." But crucially, because the child is not told this rule by the experimenter, he or she must first infer it. Therefore, the windows task has two distinct requirements: (a) infer the rule "point to the empty box" and, once the rule is inferred, (b) use the rule by holding it in mind while inhibiting the prepotent response of pointing to the treat. In this study, the authors sought to determine which of these two requirements was responsible for poor performance on the windows task. They compared the performance of 3(1/2)-year-olds (N=40) on four tasks: the standard windows task, a version of the windows task that required rule use but not rule inference, and two versions of the day-night task that also required rule use but not rule inference. The relative performance on these four tasks and the pattern of correlations among them suggested that children had difficulty in inferring a rule that enables them to pass the task, whereas they had little difficulty in using the rule. Little evidence was obtained to suggest that the standard windows task requires inhibition.

Child, Preschool↗
PubMed2004

Application of liquid chromatography-mass spectrometry to monitoring plasma cyclophosphamide levels in phase I trial cancer patients.

A specific and efficient liquid chromatography-mass spectrometry (LC-MS) method was established for monitoring patient plasma cyclophosphamide levels in a phase I trial of an oral cyclophosphamide-based combination chemotherapy regimen. An Agilent 1100 Series LC-MSD system (Agilent Technologies, Avondale, PA, USA), with a single quadrupole mass detector using a positive atmospheric pressure chemical ionization (APCI) interface and single ion monitoring at m/z 261, was used. Chromatography was performed using a LUNA C8 5 microm 30 x 4.6 mm stainless steel column (Phenomenex, Torrance, CA, USA) and a mobile phase of aqueous acetonitrile pumped at a flow rate of 0.7 mL/min. High-throughput solid-phase sample extraction was performed using a Gilson ASPEC XL4 system (Gilson Medical, Middleton, WI, USA) controlled by prestored programs. The standard curve for cyclophosphamide was linear over the concentration range 0.026-1.08 microg/mL (r(2) > 0.994). Intra- and interassay accuracy and precision were 97-107 and 3-10%, respectively. The limit of detection was determined to be 0.01 microg/mL. Single ion monitoring at m/z 261 provided a high degree of specificity without interference from the matrix or other chemotherapy drugs. Automated sample processing allowed the analysis of a large number of plasma samples from a clinical trial of repeated daily oral dosing of cyclophosphamide. One hour after dosing, cyclophosphamide was detected in 98 of 106 plasma specimens at concentrations ranging between 0.03 and 4.88 microg/mL. Twenty-four hours after dosing, cyclophosphamide was detected in 72 of 77 plasma specimens at concentrations ranging between 0.06 and 3.13 microg/mL. There were no time-dependent changes in cyclophosphamide concentration during the 43 day period of repeated daily oral dosing. There was no correlation between cyclophosphamide dose and plasma concentration, despite the wide range of doses given in the clinical trial (50-125 mg/m(2)). We conclude that a solid-phase extraction LC-MS technique was validated for determining cyclophosphamide in human plasma. Interoccasion variability in the rate of oral absorption and in the clearance of systemically available drug may have contributed to the wide range of cyclophosphamide concentrations found at 1 and 24 h after tablet ingestion.

Antineoplastic Agents↗
PubMed2003

An experimental bivalent peptide vaccine against schistosomiasis and fascioliasis.

With a view to producing peptides capable of inducing a protective immune response against Schistosoma mansoni and Fasciola hepatica, the sequence and structure of the protective antigens Sm14 and Fh15 were analyzed. Their C-termini showed a high level of sequence conservation which, together with models for their three-dimensional structures, aided in peptide selection. Vaccination trials in Swiss mice challenged with S. mansoni cercaria or F. hepatica metacercaria showed that peptides which included the sequences VTVGDVTA or EKNSESKLTQ were capable of inducing levels of protection equivalent to the recombinant form of Sm14. These peptides may represent an alternative to r-Sm14 for the development of a bivalent anti-helminth vaccine.

Amino Acid Sequence↗
PubMed2002

Clinical pharmacology of the novel marine-derived anticancer agent Ecteinascidin 743 administered as a 1- and 3-h infusion in a phase I study.

Ecteinascidin 743 (ET-743) is an anticancer agent derived from the Caribbean tunicate Ecteinascidia turbinata. In the present article, the pharmacokinetics and pharmacodynamics of ET-743 are described within a phase I study. Forty patients with solid tumors initially received ET-743 as a 1-h i.v. infusion every 21 days at nine dose levels (50-1100 microg/m(2)). The maximal tolerated dose (MTD) was 1100 microg/m(2), with thrombocytopenia and fatigue as dose-limiting toxicities (DLTs). As this MTD was substantially lower than in parallel phase I studies, dose escalation continued using a prolonged, 3-h infusion. Thirty-two patients were entered at five dose levels (1000-1800 microg/m(2)). The MTD was 1800 microg/m(2) with pancytopenia and fatigue as DLTs. The recommended phase II dose was 1650 microg/m(2) given over 3 h at which 12 patients were treated. Pharmacokinetic monitoring was performed for both treatment schedules. Non-compartmental pharmacokinetic parameters at the recommended dose with the 3-h infusion were (mean value+/-SD): clearance 87+/-30 l/h and mean elimination half-life 26+/-7 h. Pharmacokinetics were linear at the dose range tested with this schedule. The percentage decrease in platelets, white blood cells and neutrophils correlated with the area under the plasma concentration versus time curve (AUC), dose and maximal plasma concentration (C(max)). Hepatic toxicity increased with dose, AUC and C(max). Administration of 1650 microg/m(2) ET-743 over 3 h seemed clinically feasible; pharmacokinetics were linear with this schedule. Hepatic and hematological toxicities correlated with exposure to ET-743.

Adult↗
PubMed2002

Clinical and mycological responses to fluconazole and fluconazole MIC in oropharyngeal candidiasis in HIV-infected patients.

INTRODUCTION: OPC is a common opportunistic infection in HIV-infected patients. Although some patients are asymptomatic, progression of the disease may occur leading to esophageal candidiasis. Fluconazole resistant candidiasis has been reported in several international studies. OBJECTIVES: This study aimed to test the MICs (minimal inhibitory concentrations) to fluconazole of Candida species isolated from mouthwash specimens of 54 HIV positive patients with oral candidiasis. Clinical and mycological responses to fluconazole were also assessed in 16 patients. MATERIAL AND METHOD: This was a prospective study. Mouthwash specimens were cultured on sabouraud dextrose agar twice. Candida species identification was performed and MICs for fluconazole were obtained using NCCLS guidelines. Clinical and mycological responses were assessed on day 14 and 42 in 16 patients who received a 14-day course of fluconazole. RESULTS: 48/54 patients (88.89%) were found to carry pure C. albicans. The other 6 patients (11.11%) had mixed Candida species on cultures. Among these 6 patients, 5 patients had mixed C. albicans and C. glabrata, and 1 patient had C. albicans and C. krusei. Fluconazole MICs of C. albicans, C. glabrata, and C. krusei ranged from 0.125-32 (median=0.250), 4-64 (median=2), and 8 g/L respectively. This study showed that the MICs to fluconazole of oropharyngeal Candida was a good predictor of the therapeutic responses.

Adult↗