Search PubMed⌕ Search

Biomedical subjects

A Parry

Publications and source records attributed to A Parry.

At least 19 recordsLinked to original sources
PubMed2007

A study to determine the minimum volume of blood necessary to be discarded from a central venous catheter before a valid sample is obtained in children with cancer.

BACKGROUND: The objective of this study was to determine the minimum volume of blood that should be discarded from a range of different types of central venous catheter (CVC), such that the subsequent blood sample was not diluted or contaminated by the residual intra-luminal fluid. PROCEDURE: Seventy children aged 1-19 years with central venous access inserted as part of their standard clinical treatment were recruited to this prospective study. Statistical comparison of the extent of variation in biochemical and haematological parameters observed between two blood samples taken following routine 5 ml discard blood volumes, as compared to the extent of variation between samples drawn following a 5 ml discard volume and <5 ml volumes, was carried out. RESULTS: Data indicate that the measurement error in a clinical sample obtained following a 3 ml discard volume is no different to the measurement error obtained when using a standard 5 ml discard volume. Comparable results were obtained from patients with various different types of CVC or portacath access. CONCLUSIONS: The withdrawal of a 3 ml discard volume is sufficient to ensure that the subsequent blood sample is not diluted or contaminated by residual intra-luminal fluid. This may have a significant clinical impact in paediatric oncology, where patients frequently require blood transfusions due to the haematological toxicities associated with chemotherapy. It is hoped that these results will impact on hospital policies concerning specified discard volumes taken from CVCs prior to the withdrawal of blood samples for research purposes and routine clinical analysis.

Adolescent↗
PubMed2006

The impact of a consultant anaesthetist led pre-operative assessment clinic on patients undergoing major vascular surgery.

Summary Patients undergoing major vascular surgery are at high risk of peri-operative morbidity and mortality owing to a combination of advanced age, significant co-morbidity and the nature of the surgery. A consultant-led pre-operative assessment clinic provides an opportunity to stratify these patients on the basis of risk in advance of surgery, to make timely multidisciplinary referrals where appropriate, and to prescribe medical therapies according to the current best evidence. This results in fewer last-minute cancellations for medical reasons and increased patient satisfaction, and may improve patient outcome. Such a clinic also provides an educational arena for nursing and trainee medical staff, and importantly allows those patients in whom the risks are felt to outweigh the potential benefits of surgery to be managed in a more fully informed manner.

Aged↗
PubMed2005

Pharmacokinetics and metabolism of ifosfamide in relation to DNA damage assessed by the COMET assay in children with cancer.

The degree of damage to DNA following ifosfamide (IFO) treatment may be linked to the therapeutic efficacy. The pharmacokinetics and metabolism of IFO were studied in 19 paediatric patients, mostly with rhabdomyosarcoma or Ewings sarcoma. Ifosfamide was dosed either as a continuous infusion or as fractionated doses over 2 or 3 days. Samples of peripheral blood lymphocytes were obtained during and up to 96 h after treatment, and again prior to the next cycle of chemotherapy. DNA damage was measured using the alkaline COMET assay, and quantified as the percentage of highly damaged cells per sample. Samples were also taken for the determination of IFO and metabolites. Pharmacokinetics and metabolism of IFO were comparable with previous studies. Elevations in DNA damage could be determined in all patients after IFO administration. The degree of damage increased to a peak at 72 h, but had returned to pretreatment values prior to the next dose of chemotherapy. There was a good correlation between area under the curve of IFO and the cumulative percentage of cells with DNA damage (r2=0.554, P=0.004), but only in those patients receiving fractionated dosing. The latter patients had more DNA damage (mean+/-s.d., 2736+/-597) than those patients in whom IFO was administered by continuous infusion (1453+/-730). The COMET assay can be used to quantify DNA damage following IFO therapy. Fractionated dosing causes a greater degree of DNA damage, which may suggest a greater degree of efficacy, with a good correlation between pharmacokinetic and pharmacodynamic data.

Adult↗
PubMed2005

Outcome of acute promyelocytic leukemia treated with all trans retinoic acid and chemotherapy in elderly patients: the European group experience.

We analyzed the outcome of patients aged more than 60 included in a multicenter trial in newly diagnosed acute promyelocytic leukemia (APL93 trial), which tested the role of early addition of chemotherapy to all trans retinoic acid (ATRA) and of maintenance with ATRA and/or low-dose chemotherapy. In total, 129/533 (24.2%) patients included in this trial were older than 60. The CR rate was 86% in patients older than 60 as compared to 94.5% in younger patients (P=0.0014), due to a higher incidence of early deaths in elderly patients. The 4-year incidence of relapse was 15.6% in adults older than 60 and 23.2% in younger adults although most elderly patients received less intensive consolidation chemotherapy. However, 18.6% of the patients older than 60 years who achieved CR died in CR, mainly from sepsis during consolidation course or maintenance treatment, as compared to 5.7% of younger adults (P<0.001). Thus, overall 4-year survival of elderly patients was 57.8% as compared to 78% in younger adults (P<0.0001). APL in elderly patients appears as sensitive to ATRA-Chemotherapy based regimen as in younger adults. Less favorable outcome is mainly due to an increase of early deaths and to toxicity of consolidation treatment, strongly suggesting a beneficial role for less intensive consolidation chemotherapy and possibly introduction of arsenic derivates in the treatment of APL in the elderly.

Adolescent↗
PubMed2005

Balance disorder and traumatic brain injury: preliminary findings of a multi-factorial observational study.

The pathophysiology of TBI suggests that balance disorder in this population may be associated with multi-system dysfunction, but this has not been widely explored in the literature. This study was undertaken to begin to describe the nature of balance disorder across the TBI population. A clinically-based observational design was employed and data gathered by a standardized process of structured observation. Twenty-seven subjects were recruited across a range of injury severities. The sample was skewed towards mild/moderate injury with a mean summated GCS score of 9.6. Deficits were observed across a wide range of domains at both individual and group level and the overall level of balance dysfunction was high. Summary results are reported here and a more detailed analysis of individual cases is underway. Additional cross-disciplinary research is required to further develop understanding of the nature of balance disorder in this population and to develop appropriate methods of clinical assessment.

Adult↗
PubMed2004

Autologous and allogeneic stem-cell transplantation as salvage treatment of acute promyelocytic leukemia initially treated with all-trans-retinoic acid: a retrospective analysis of the European acute promyelocytic leukemia group.

PURPOSE: To retrospectively determine the outcome of acute promyelocytic leukemia (APL) patients who underwent autologous or allogeneic stem-cell transplantation (SCT) during second complete remission. PATIENTS AND METHODS: Of 122 relapsing patients included in two successive multicenter APL trials who achieved hematological second complete remission (generally after a salvage regimen of all-trans-retinoic acid [ATRA] combined with chemotherapy), 73 (60%) received allogeneic (n = 23) or autologous (n = 50) SCT. RESULTS: Seven-year relapse-free survival (RFS), event-free survival (EFS), and overall survival (OS) in the autologous SCT group were 79.4%, 60.6%, and 59.8%, respectively, with a transplant-related mortality (TRM) of 6%. Of the 28 and two patients autografted with negative and positive, respectively, reverse transcriptase-polymerase chain reaction before auto SCT, three (11%) and one relapsed, respectively. In the allogeneic SCT group, 7-year RFS, EFS, and OS were 92.3%, 52.2%, and 51.8%, respectively, with 39% TRM. OS was significantly better in the autologous SCT group than in the allogeneic SCT group (P = .04), whereas RFS and EFS did not differ significantly (P = .19 and P = .11, respectively). In patients not receiving transplantation, 7-year RFS, EFS, and OS were 38%, 30.4%, and 39.5%, respectively. CONCLUSION: These retrospective data suggest that autologous SCT is very effective in APL relapsing after treatment with ATRA if performed in molecular remission. Allogeneic SCT yields few relapses, but it is associated with high TRM when performed after salvage with very intensive chemotherapy. Salvage with arsenic trioxyde, which has lower toxicity, should further improve the outcome of relapsing APL, especially before allogeneic SCT.

Adult↗
PubMed2004

Outcome of childhood acute promyelocytic leukemia with all-trans-retinoic acid and chemotherapy.

PURPOSE: To determine the results of treatment combining all-trans-retinoic acid (ATRA) and chemotherapy (CT) in childhood acute promyelocytic leukemia (APL). PATIENTS AND METHODS: Children (< 18 years) with newly diagnosed APL were included in the APL93 trial, treated by ATRA followed or combined with daunorubicin-cytarabine, and then randomly assigned between no maintenance, intermittent ATRA, continuous CT, or both. RESULTS: Of the 576 patients included in APL93 trial, 31 (5%) were children, including 22 girls (71%) and nine boys (29%). Thirty of the children (97%) obtained complete remission (CR). ATRA syndrome occurred in four children (13%), who all achieved CR, and headaches occurred in 12 children (39%), with signs of pseudotumor cerebri in five children (16%). Seven patients (23%) relapsed. None of the eight patients who received both ATRA and CT for maintenance relapsed. All relapsing patients achieved a second CR. Twenty-two patients remained in first CR after 43+ to 96+ months, six remained in second CR after 17+ to 66+ months, and three patients had died. The 5-year event-free survival (EFS), relapse, and overall survival rates were 71%, 27%, and 90%, respectively. No difference between adults and children included in the APL93 trial was seen for CR rate, 5-year relapse rate, EFS, and overall survival, but significantly better survival was seen in children after adjustment on WBC counts (P =.02) and incidence of microgranular M3 variant (P =.04). CONCLUSION: ATRA combined with CT for induction and also probably for maintenance provides as favorable results in children with APL as in adults and currently constitutes the reference first-line treatment in both age groups.

Adolescent↗
PubMed2004

Estimation of glomerular filtration rate in paediatric cancer patients using 51CR-EDTA population pharmacokinetics.

Estimation of glomerular filtration rate (GFR) using the clearance of chromium 51 EDTA ((51)Cr-EDTA) (or other radiolabelled isotopes) is reliable, but invasive and not always practicable. Mathematical models have been devised for estimating GFR using readily obtainable patient characteristics. Unfortunately, these models were developed using various patient populations and may not provide the optimal prediction of GFR in children with cancer. The current study uses population pharmacokinetics to determine the relationship between (51)Cr-EDTA clearance, and patient covariates in 50 paediatric cancer patients. These models were validated using a separate group of 43 children and were compared with previously published models of renal function. Body size was the major determinant of (51)Cr-EDTA clearance and inclusion of weight or surface area reduced the residual variability between individuals (coefficient of variation) from 61 to 32%. Serum creatinine was the only other parameter that significantly improved the model. Mean percentage error values of -5.0 and -1.1% were observed for models including weight alone or weight and creatinine, respectively, with precision estimates of 21.7 and 20.0%. These simple additive models provide a more rationale approach than the use of complex formulae, involving additional parameters, to predict renal function.

Adolescent↗
PubMed2003

Beta-Interferon treatment does not always slow the progression of axonal injury in multiple sclerosis.

Progression of disability in multiple sclerosis (MS) appears related to axonal damage, which is at least in part associated with white matter lesions. Beta-interferon (BIFN) substantially reduces new inflammatory activity in MS and a recent report suggested that it may reverse a component of axonal injury. To test the generalisability of this conclusion, particularly in a population with relatively active disease, we used magnetic resonance spectroscopy measures to test whether BIFN can reverse or arrest progression of axonal injury in patients with MS. Eleven patients with a history of active (median, 1.5 relapses/year) relapsing-remitting MS were treated with BIFN and responses to treatment were monitored with serial MRI and single voxel magnetic resonance spectroscopic measurements of relative concentrations of brain N-acetylaspartate (NAA), a measure of axonal integrity from a central, predominantly white matter brain region. BIFN treatment was associated with a significant reduction in relapse rate (p = 0.007) and white matter water T2 relaxation time (p = 0.047) over 12 months. Also consistent with a treatment effect, white matter T2-hyperintense lesion loads did not increase. However, the central white matter NAA/creatine ratio (NAA/Cr, which was reduced over 16 % in patients relative to healthy controls at the start of treatment), continued to decrease in the patients over the period of observation (mean 6.2 % decrease, p = 0.02). For individual patients the magnitude of the NAA/Cr decrease was correlated with the frequency of relapses over the two years prior to treatment (r = -0.76, p = 0.006). These data suggest that reduction of new inflammatory activity with BIFN does not invariably halt progression of axonal injury. Nonetheless, there appears to be a relationship between the rate of progression of axonal injury and relapse rate over the previous two years. The consequences of reduced inflammation on pathological progression relevant to disability therefore may be present, but substantially delayed. Alternatively, distinct mechanisms may contribute to the two processes.

Adult↗
PubMed2003

MRI brain T1 relaxation time changes in MS patients increase over time in both the white matter and the cortex.

OBJECTIVE: To test the sensitivity of whole-brain T1 relaxometry to the evolution of pathological changes in multiple sclerosis (MS). BACKGROUND: T1-weighted hypointense lesion load in the brains of patients with MS is associated with axonal loss. Other work has shown that T1 measurements may provide information complementary to existing imaging techniques, such as magnetization transfer imaging. METHODS: The authors studied 14 MS patients twice over a median time interval of 19.5 months (range, 14-22 months). Structural images and whole-brain T1 maps using a novel rapid-scanning technique (3 min/study) were performed at 3 T. Analysis focused on defining changes separately in the lesional and normal-appearing white matter (NAWM) and in the cortical gray matter. RESULTS: At baseline, there was an inverse relationship between disease duration and the NAWM T1 histogram peak height (r = -0.75, P = .03). The total white matter T1 histogram peak height decreased over time (P < .001). This could be accounted for by changes in the NAWM (P < .03). There also was a decrease (6%) in the mean (11 of 14 patients, P = .004) and in the median (7%) (13 of 14 patients, P < .001) neocortical gray matter T1 over the follow-up period. CONCLUSIONS: Brain T1 maps can be generated quickly and are sensitive to pathological changes over time. T1 values in both the gray and the white matter at the baseline visit were related to disease duration, suggesting that the T1 changes are clinically relevant. Although the absolute values will be different, it is likely that similar changes will be able to be detected at 1.5 T. The role of T1 measurement as a magnetic resonance imaging outcome measure in clinical trials now should be explored.

Adult↗
PubMed2003

Roles for imaging in understanding the pathophysiology, clinical evaluation, and management of patients with mitochondrial disease.

Primary mitochondrial disorders remain uncommon, but they enter into the differential diagnosis for a broad range of syndromes. Functional and structural imaging methods offer important clinical tools for patient assessment when these diseases are suspected. Although the findings are not specific, in the appropriate clinical context, these tests can guide the use of more specific or invasive investigations. They have provided considerable information concerning the underlying pathophysiology of this heterogeneous range of disorders. Monitoring these changes potentially facilitates the identification of new therapies and their individualization.

Humans↗
PubMed2002

White matter and lesion T1 relaxation times increase in parallel and correlate with disability in multiple sclerosis.

Previous studies have established the clinical relevance of hypointense lesions ("black holes") on T1-weighted MRI as a surrogate marker for pathological change [36]. In contrast to measuring the volume of "black holes", the direct measurement of T1 values allows an objective assessment of the changes contributing to hypointensity both in the focal lesions and in the normal appearing white matter (NAWM). The aims of this study were first, to determine the relationship between T1 values in the NAWM and in discrete lesions, second, to test the relationship between white matter T1 changes and measures of disability and third, to determine whether pathology leading to T1 change occurred in thalamic grey matter of patients with multiple sclerosis. 24 patients with clinically definite multiple sclerosis (13 with relapsing-remitting multiple sclerosis and 11 with secondary progressive multiple sclerosis) and 11 controls participated. White matter T1 histograms and mean T1 values for the thalamus were generated from whole brain T1 relaxation time maps measured using a novel echo-planar imaging based MRI sequence at 3Tesla. Tissue segmentation based on T2- and T1-weighted images allowed independent study of changes in lesions and NAWM. White matter T1 histograms from the patient group showed a reduced peak height and a shift towards higher T1 values (p = 0.028) relative to controls. The mean thalamic T1 was greater for secondary progressive patients than for healthy controls (p = 0.03). Mean white matter T1 values correlated significantly with disability (r = 0.48, p = 0.02). The mean T1 value in the T1-hypointense lesions correlated strongly with the mean T1 value in the NAWM (r = 0.80, p < 0.001). No significant relationship was found between mean white matter T1 value and cerebral volume (r = -0.23, p = 0.31). The T1 measurements extend previous observations suggesting that changes in the NAWM occur in parallel with pathology in lesions of MS. T1 measurements of either the total or NAWM therefore may provide a potentially observer- and scanner- independent marker of pathology relevant to disability in MS.

Adult↗
PubMed2002

Is subjective shortening in human memory unique to time representations?

Three experiments compared forgetting of the duration of a bar-like visual stimulus with forgetting of its length. The main aim of the experiments was to investigate whether subjective shortening (a decrease in the subjective magnitude of a stimulus as its retention interval increased) was observable in length judgements as well as in time judgements, where subjective shortening has been often observed previously. On all trials of the three experiments, humans received two briefly presented coloured bars, separated by a delay ranging from 1 to 10 s, and the bars could differ in length, duration of presentation, or both. In Experiment 1 two groups of subjects made either length or duration judgements, and subjective shortening-type forgetting functions were observed only for duration. Experiments 2 and 3 used the same general procedure, but the stimuli judged could differ both in length and duration within a trial, and different subject groups (Experiment 2) or the same subjects in two conditions (Experiment 3) made either length or duration judgements of stimuli, which were on average physically identical. Subjective shortening was only found with duration, and never with length, supporting the view that subjective shortening may be unique to time judgements.

Adult↗
PubMed2001

A phase I study in paediatric patients to evaluate the safety and pharmacokinetics of SPI-77, a liposome encapsulated formulation of cisplatin.

Pre-clinical studies indicate that cisplatin encapsulated in STEALTH((R))liposomes (SPI-77) retains anti-tumour activity, but has a much reduced toxicity, compared to native cisplatin. A phase I study was conducted to determine the toxicity and pharmacokinetics of SPI-77 administered to children with advanced cancer not amenable to other treatment. Paediatric patients were treated at doses ranging from 40 to 320 mg m(-2)by intravenous infusion every 4 weeks. Blood samples taken during, and up to 3 weeks after, administration and plasma and ultrafiltrate were prepared immediately. Urine was collected, when possible, for 3 days after administration. SPI-77 administration was well tolerated with the major toxicity being an infusion reaction which responded to modification of the initial infusion rate of SPI-77. Limited haematological toxicity and no nephrotoxicity were observed. No responses to treatment were seen during the course of this phase I study. Measurement of total plasma platinum showed that cisplatin was retained in the circulation with a half life of up to 134 h, with maximum plasma concentrations approximately 100-fold higher than those reported following comparable doses of cisplatin. Comparison of plasma and whole blood indicated that cisplatin was retained in the liposomes and there was no free platinum measurable in the ultrafiltrate. Urine recovery was less than 4% of the dose administered over 72 h. Results from this phase I study indicate that high doses of liposomal cisplatin can safely be given to patients, but further studies are required to address the issue of reformulation of liposomally bound cisplatin.

Adolescent↗
PubMed2001

Age-dependent and hypoxia-related differences in myocardial protection during pediatric open heart surgery.

BACKGROUND: Current cardioplegic protection techniques used in pediatric cardiac surgery do not take into consideration age and cyanotic differences. The aim of the present work was to address this question by monitoring clinical outcome, myocardial metabolism, and reperfusion injury in pediatric patients protected by cold-crystalloid cardioplegia. METHODS AND RESULTS: Fifty-eight patients (31 children and 27 infants) with or without hypoxic stress (cyanosis) undergoing open heart surgery with cold-crystalloid cardioplegia were included in the study. Clinical outcome measures assessed included inotropic and ventilatory support, intensive care, and hospital stay. Ischemia-induced changes in metabolism (adenine nucleotides, purines, lactate, and amino acids) were determined in ventricular biopsies collected at the beginning and end of ischemic time (cross-clamp time). Reperfusion injury was assessed by measuring postoperative serial release of troponin I. Evidence was observed of ischemic stress during cardioplegic arrest in children and infants as shown by significant changes in cellular metabolites. Compared with infants, children had significantly less reperfusion injury and better clinical outcome, and these factors were related to duration of ischemic time. Cyanosis did not influence outcome in infants, but cyanotic children showed worse reperfusion injury and clinical outcome than acyanotic children. CONCLUSIONS: Extent of myocardial protection with cold-crystalloid cardioplegia in pediatric open heart surgery is dependent on age and degree of cyanosis.

Age Factors↗
PubMed2001

Influence of cellular factors and pharmacokinetics on the formation of platinum-DNA adducts in leukocytes of children receiving cisplatin therapy.

The formation of platinum (Pt)-DNA adducts is thought to be crucial to the antitumor activity of cisplatin, and relationships between adduct formation in peripheral blood leukocytes (PBLs) and response to cisplatin therapy have been reported. The current study directly tests, for the first time, whether pharmacokinetic or other factors predominantly determine the drug-target interaction of cisplatin in a pediatric patient population. Cisplatin pharmacokinetics and Pt-DNA adduct formation in PBLs were determined in 10 children in parallel with measurement of adduct levels after incubation of pretreatment blood samples with cisplatin in vitro. Total and unbound plasma Pt concentrations were determined by atomic absorption spectrophotometry and adduct measurements performed by competitive ELISA. Pt-DNA adduct levels determined after cisplatin treatment showed considerable interindividual variation (peak levels at 24 h ranged from 0.15 to 1.31 nmol/g DNA) and correlated strongly with adduct levels determined after incubation of pretreatment whole blood with cisplatin (r = 0.92; P = 0.0002). No significant correlation was observed between in vivo adduct formation and either unbound or total cisplatin plasma concentrations (r = 0.14 and 0.18, respectively). A correlation was also observed between the degree of myelosuppression, as determined by WBC nadirs measured over a 14-day period after cisplatin treatment, and the extent of adduct formation, with greater WBC toxicity observed in patients with higher levels of Pt-DNA adducts (P = 0.010). These preliminary results provide evidence that interpatient variation in formation of Pt-DNA adducts in PBLs of children is determined by host-specific factors other than cisplatin pharmacokinetics. These results imply that analysis of adducts in PBLs after incubation of pretreatment blood samples with cisplatin may be used to predict in vivo adduct levels, leukopenia, and, potentially, response to cisplatin therapy.

Adolescent↗