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Biomedical subjects

D Green

Publications and source records attributed to D Green.

At least 19 recordsLinked to original sources
PubMed2006

Pten (phosphatase and tensin homologue gene) haploinsufficiency promotes insulin hypersensitivity.

AIMS/HYPOTHESIS: Insulin controls glucose metabolism via multiple signalling pathways, including the phosphatidylinositol 3-kinase (PI3K) pathway in muscle and adipose tissue. The protein/lipid phosphatase Pten (phosphatase and tensin homologue deleted on chromosome 10) attenuates PI3K signalling by dephosphorylating the phosphatidylinositol 3,4,5-trisphosphate generated by PI3K. The current study was aimed at investigating the effect of haploinsufficiency for Pten on insulin-stimulated glucose uptake. MATERIALS AND METHODS: Insulin sensitivity in Pten heterozygous (Pten(+/-)) mice was investigated in i.p. insulin challenge and glucose tolerance tests. Glucose uptake was monitored in vitro in primary cultures of myocytes from Pten(+/-) mice, and in vivo by positron emission tomography. The phosphorylation status of protein kinase B (PKB/Akt), a downstream signalling protein in the PI3K pathway, and glycogen synthase kinase 3beta (GSK3beta), a substrate of PKB/Akt, was determined by western immunoblotting. RESULTS: Following i.p. insulin challenge, blood glucose levels in Pten(+/-) mice remained depressed for up to 120 min, whereas glucose levels in wild-type mice began to recover after approximately 30 min. After glucose challenge, blood glucose returned to normal about twice as rapidly in Pten(+/-) mice. Enhanced glucose uptake was observed both in Pten(+/-) myocytes and in skeletal muscle of Pten(+/-) mice by PET. PKB and GSK3beta phosphorylation was enhanced and prolonged in Pten(+/-) myocytes. CONCLUSIONS/INTERPRETATION: Pten is a key negative regulator of insulin-stimulated glucose uptake in vitro and in vivo. The partial reduction of Pten due to Pten haploinsufficiency is enough to elicit enhanced insulin sensitivity and glucose tolerance in Pten(+/-) mice.

Animals↗
PubMed2006

Coagulation factor VII gene haplotypes, obesity-related traits, and cardiovascular risk in young women.

BACKGROUND: Associations between common F7 haplotypes, plasma factor VII (FVII) levels, and cardiovascular risk have recently been reported in population studies involving predominantly European men. METHODS: We assessed associations between F7 haplotypes and cardiovascular risk in two US population-based studies: a case-control study of these alleles related to a decreased risk of arterial thrombotic outcomes such as myocardial infarction (MI) in young-to-middle-aged women (n = 671), and a cohort study of cardiovascular disease risk factors in young women (n = 1040). RESULTS: The high-expression F7 haplotype B (containing the promoter variant allele -402A) was associated with an increased FVII level among controls, but not with MI risk. Women carrying a> or =1 copy of the low FVII expression level haplotype C (containing the -401T/-323del/-122C and Gln353 alleles) had decreased FVII levels and decreased risk of MI (odds ratio 0.54, 95% CI 0.31-0.93) compared with women homozygous for the most common haplotype A. Haplotype C was also associated with a decreased body mass index (BMI) and an increased high-density lipoprotein (HDL) cholesterol level, but not with MI risk after adjustment for these metabolic risk factors. In a cohort study composed of young US women, individuals homozygous for haplotype C had a lower BMI and lower systolic blood pressure, but the association between the F7 haplotype and HDL cholesterol was not confirmed. CONCLUSION: Common FVII haplotypes may contribute to the risk of MI in women, but the mechanisms appear complex. The association between F7 haplotypes and MI susceptibility may be mediated in part through an influence on atherogenic risk factors such as BMI.

Adolescent↗
PubMed2006

Plasma hemostatic factors and endothelial markers in four racial/ethnic groups: the MESA study.

BACKGROUND: Hemostatic factors and endothelial markers may play some role in racial/ethnic differences in cardiovascular disease (CVD) rates. However, little information exists on hemostatic factors and endothelial markers across racial/ethnic groups. OBJECTIVES: To describe, in four American racial/ethnic groups (Caucasian, Black, Hispanic, and Chinese), mean levels of selected hemostatic factors and endothelial markers. PATIENTS AND METHODS: Multi-ethnic Study of Atherosclerosis baseline data were used (participant age: 45-84 years). Sex-specific analysis of covariance models, and t-tests for pairwise comparisons, were used to compare means of factors and markers. Adjustments were made for demographics and traditional CVD risk factors. Differences were significant at P < 0.05. RESULTS: Blacks had the highest levels of factor VIII, D-Dimer, plasmin-antiplasmin (PAP), and von Willebrand factor, among the highest levels of fibrinogen and E-selectin (women only), but among the lowest levels of intercellular adhesion molecule 1 (ICAM-1), and, in men, the lowest levels of plasminogen activator inhibitor-1 (PAI-1). Whites and Hispanics tended to have intermediate levels of factors and markers, although they had the highest levels of ICAM-1, and Hispanics had the highest mean levels of fibrinogen and E-selectin (women only). Chinese participants had among the highest levels of PAI-1, but the lowest, or among the lowest, of all other factors and markers. No soluble thrombomodulin differences were observed. CONCLUSIONS: In this large cohort, hemostatic factor and endothelial marker mean levels varied by race/ethnicity, even after adjustment for traditional CVD risk factors.

Aged↗
PubMed2006

Does hospital cleanliness correlate with methicillin-resistant Staphylococcus aureus bacteraemia rates?

Publicly available data for all National Health Service hospitals in England were used to examine whether there is a link between hospital cleanliness and rates of meticillin-resistant Staphylococcus aureus (MRSA) bacteraemia. It was not possible to demonstrate a consistent relationship between hospital cleanliness, as measured by weighted Patient Environment Action Team (PEAT) scores, and the incidence of MRSA bacteraemia. The large sizes of the data sets make it unlikely that a true correlation was missed. While a high standard of hospital cleanliness is a worthwhile goal, it is not helpful to repeatedly link MRSA control measures with improvements in standards of environmental cleanliness.

Bacteremia↗
PubMed2006

A pilot study of psychopathology in Developmental Coordination Disorder.

BACKGROUND: This paper explores the prevalence of emotional and behavioural disorders in children referred to a Community Paediatric Occupational Therapy service for assessment and treatment of problems with development of motor skills. METHODS: Parents of 47 children from a clinical sample of children who had been identified with Developmental Coordination Disorder (DCD) returned the Strengths and Difficulties Questionnaire (SDQ)--a brief measure of the pro-social behaviour and psychopathology that can be completed by parents, teachers or youths. RESULTS: Significant emotional and behavioural problems were reported by 29 parents (62%) with a further six (13%) reporting problems in the borderline range. Seven children (15%) were without significant problems in one or more area although only four of these (9%) were outside the borderline range for all of the sub-domains of the SDQ. DISCUSSION: A significant proportion of children with DCD were reported by their parents to be at risk of psychopathology. Further research is needed to understand the relationship between motor difficulties and emotional and behavioural symptoms; however, it is recommended that interventions for children with DCD should support mental health and behavioural problems as well as motor development.

Analysis of Variance↗
PubMed2005

Role of environmental cleaning in controlling an outbreak of Acinetobacter baumannii on a neurosurgical intensive care unit.

An outbreak of Acinetobacter baumannii colonization and infection occurred in 19 patients over a 14-month period during 1998-1999 on a neurosurgical intensive care unit. During efforts to control the outbreak a significant correlation was observed between the number of environmental isolates of A. baumannii obtained during each monthly screening and the number of patients with A. baumannii colonization/infection in the same calendar month (P=0.004). Use of 1000 ppm hypochlorite solution and the introduction of new cleaning protocols reduced the number of environmental isolates. Failure to maintain low levels of environmental contamination with A. baumannii resulted in increases in patient colonization. This study showed that high standards of cleaning play an integral role in controlling outbreaks of A. baumannii in the intensive care unit setting.

Acinetobacter Infections↗
PubMed2005

Arsenic levels in the soils and macrophytes of the 'Entremuros' after the Aznalcóllar mine spill.

In April 1998, a holding lagoon containing pyrite ore processing waste rich in arsenic, failed and released 5-6 million m(3) of highly polluting sludge and acidic water. Over 2700 ha of the internationally important Doñana National and Natural Parks were contaminated. The area of Natural Park to sustain the greatest impact was known as the Entremuros. This paper presents 0-5 cm soil monitoring data from the Entremuros, from sampling campaigns 6 and 18 months after the disaster; as well as macrophyte root, rhizome and stem data from samples taken 18 months after the spill. Results show a clear, decreasing, north-south arsenic soil pollution trend, both 6 and 18 months after the spill, and suggest a small reduction in total soil arsenic levels occurred over time; although a significant increase in extractable arsenic is also noted. The two macrophytes (Typha dominguensis and Scirpus maritimus) studied herein are not accumulating arsenic in stem parts, however, accumulation of arsenic on iron plaque on the roots of these plants may be occurring. Further work is recommended in order to determine the ecotoxicological significance of this process in relation to the avian food-chains of Doñana, and elsewhere.

Accidents↗
PubMed2005

Rituximab for autoimmune haemophilia: a proposed treatment algorithm.

We previously reported durable complete responses following brief courses of rituximab and prednisone with or without cyclophosphamide in four patients with autoimmune haemophilia and inhibitor titres of 5-60 BU. We report here responses to this monoclonal anti-CD20 antibody in four additional patients, including two patients with inhibitor titres >200 BU. Factor VIII levels became normal 2-35weeks after 4 or 8 weekly doses of rituximab, brief courses of prednisone and in one patient immunoglobulin. Complete responses are ongoing at 10 months in two patients. Two patients relapsed: a patient whose initial inhibitor titre was 525 BU relapsed at 3.5 months and a long-term prednisone-dependent patient at 8.5 months. Both responded to second courses of rituximab and prednisone and are in remission. Our experience suggests that rituximab is a safe and effective addition to immunosuppression with prednisone and cyclophosphamide to treat autoimmune haemophilia, and may permit early discontinuation or even avoidance of these potentially toxic agents. High-titre inhibitor patients, however, may require multiple courses of rituximab or the addition of cyclophosphamide. Pending randomized studies, we propose an algorithm based on our experience and other reports for incorporating rituximab in the treatment of this rare disorder.

Aged↗
PubMed2005

Factor VIII inhibitor associated with peginterferon.

We present a case of a 53-year-old black male who developed a factor VIII inhibitor during his treatment for hepatitis C virus infection with peginterferon. The development of inhibitors against factor VIII during peginterferon therapy has been rarely reported. We have reviewed the current literature and the following case presentation provides the first demonstration, to our knowledge, in which chronic exposure to peginterferon is associated with an acquired factor VIII inhibitor.

Antibodies, Monoclonal↗
PubMed2005

Sequential avulsion of the anterior inferior iliac spine in an adolescent long jumper.

We present here an unusual case of a sequential avulsion fracture of the anterior inferior iliac spine (AIIS), occurring first in the right and then the left AIIS, during long jump attempts. The case of a 17 year old boy with pain around his right groin, which first occurred during a long jump attempt, is presented. Radiographic examination revealed an avulsion fracture of the right AIIS. After conservative treatment, full athletic activity was allowed 2 months after the injury. However, 4 months later the patient returned with a similar pain in the opposite side of his groin. Radiographs revealed another fracture of the left AIIS. The boy underwent the same treatment protocol; he was examined with isokinetic dynamometry. No complication or re-injury occurred during the 2 year follow up period. In the present study, we introduce the first case of a sequential bilateral AIIS avulsion fracture caused by a long jump.

Adolescent↗
PubMed2004

Role of environmental cleaning in controlling an outbreak of Acinetobacter baumannii on a neurosurgical intensive care unit.

An outbreak of Acinetobacter baumannii colonization and infection occurred in 19 patients over a 14-month period during 1998-1999 on a neurosurgical intensive care unit. During efforts to control the outbreak a significant correlation was observed between the number of environmental isolates of A. baumannii obtained during each monthly screening and the number of patients with A. baumannii colonization/infection in the same calendar month (P < 0.004). Use of 1000 ppm hypochlorite solution and the introduction of new cleaning protocols reduced the number of environmental isolates. Failure to maintain low levels of environmental contamination with A. baumannii resulted in increases in patient colonization. This study showed that high standards of cleaning play an integral role in controlling outbreaks of A. baumannii in the intensive care unit setting.

Acinetobacter Infections↗
PubMed2004

Comparison of 1 month with 3 months of anticoagulation for a first episode of venous thromboembolism associated with a transient risk factor.

BACKGROUND: The risk of recurrence is lower after treatment of an episode of venous thromboembolism associated with a transient risk factor, such as recent surgery, than after an episode associated with a permanent, or no, risk factor. Retrospective analyses suggest that 1 month of anticoagulation is adequate for patients whose venous thromboembolic event was provoked by a transient risk factor. METHODS: In this double-blind study, patients who had completed 1 month of anticoagulant therapy for a first episode of venous thromboembolism provoked by a transient risk factor were randomly assigned to continue warfarin or to placebo for an additional 2 months. Our goal was to determine if the duration of treatment could be reduced without increasing the rate of recurrent venous thromboembolism during 11 months of follow-up. RESULTS: Of 84 patients assigned to placebo, five (6.0%) had recurrent venous thromboembolism, compared with three of 81 (3.7%) assigned to warfarin, resulting in an absolute risk difference of 2.3%[95% confidence interval (CI) - 5.2, 10.0]. The incidence of recurrent venous thromboembolism after discontinuation of warfarin was 6.8% per patient-year in those who received warfarin for 1 month and 3.2% per patient-year in those who received warfarin for 3 months (rate difference of 3.6% per patient-year; 95% CI - 3.8, 11.0). There were no major bleeds in either group. CONCLUSION: Duration of anticoagulant therapy for venous thromboembolism provoked by a transient risk factor should not be reduced from 3 months to 1 month as this is likely to increase recurrent venous thromboembolism without achieving a clinically important decrease in bleeding.

Adult↗
PubMed2004

Phase II trial of gemcitabine concurrent with radiation for locally advanced squamous cell carcinoma of the head and neck.

BACKGROUND: Concurrent chemoradiation is the current standard of treatment for patients with advanced unresectable head and neck squamous cell carcinoma (HNSCC). Due to the potent radiosensitizing properties of gemcitabine, we decided to assess its efficacy and toxicity with concurrent radiation in patients with advanced HNSCC. PATIENTS AND METHODS: From January 1997 to December 2001, 27 patients with locally advanced HNSCC (stage III, 37%; stage IV, 63%) were enrolled. All received a course of radiotherapy (70 Gy over 7 weeks) concurrent with weekly infusions of gemcitabine at 100 mg/m2 or 50 mg/m2. RESULTS: All patients were assessable for toxicity and 26 for response. Severe mucositis (grade 3-4) was observed in 74% of patients (grade 4, 41%). Severe hematological toxicity was uncommon. Mild and moderate xerostomy was the most common late toxicity in 23 patients (85%). The median radiation dose delivered was 70 Gy (40-80 Gy), 25 patients (93%) received > or = 80% of the intended dose. Gemcitabine dose intensity was > or = 80% in only 13 (48%) patients. The rate of complete and partial responses were 61% and 27%, respectively, for an overall response rate of 88%. At a median follow-up of 13 months (range 6-62), the actuarial 3-year progression-free survival (PFS) and overall survival (OS) were 37% and 33%, respectively. The only variable associated with prolonged survival (P = 0.0001) was the degree of response. No difference was observed in response or toxicity with either gemcitabine 50 or 100 mg/m2. CONCLUSIONS: The concurrent use of radiotherapy and gemcitabine is effective but produces manageable severe mucositis in a high percentage of patients.

Adult↗
PubMed2004

Effects of all-trans retinoic acid or chemotherapy on the molecular regulation of systemic blood coagulation and fibrinolysis in patients with acute promyelocytic leukemia.

We studied the pathogenesis of the bleeding disorder in acute promyelocytic leukemia by measuring procoagulant, profibrinolytic, and proinflammatory mediators in peripheral blood and bone marrow cells from 25 previously untreated patients. Patients were induced with either all-trans retinoic acid (ATRA) or chemotherapy. Plasma levels of fibrinopeptide A (FPA), fibrin d-dimer, thrombin antithrombin (TAT) complex, prothrombin fragment 1.2 (F1.2), urokinase-type plasminogen activator (uPA), tissue-type plasminogen activator (t-PA) and plasminogen activator-inhibitor 1 (PAI-1) were measured before and after therapy, as was the cellular expression of the genes for tissue factor (TF) and interleukin-1 beta (IL-1 beta). The mean plasma levels of fibrin d-dimer, F1.2, TAT and FPA were markedly elevated prior to therapy and declined during the first 30 days of treatment with either ATRA or chemotherapy, but more rapidly and to a greater extent in patients treated with ATRA. ATRA treatment was associated with a significant decrease in TF gene expression in bone marrow cells during the first 30 days of treatment, whereas IL-1 beta gene expression, which decreased in the cells of six patients treated with either chemotherapy or ATRA, actually increased in the remaining six patients treated with either chemotherapy or ATRA. In patients with APL, treatment with either chemotherapy or ATRA rapidly ameliorates the coagulopathy, as indicated by an abrupt decline in markers of clotting activation. An increase in cytokine gene expression (e.g. IL-1 beta) may provide an explanation for the persistent hypercoagulability observed in some patients with APL, regardless of therapeutic approach. Our data confirms and extends earlier observations by others that ATRA is more effective than chemotherapy alone in rapidly reducing the procoagulant burden of APL tumor cells. However, our data also suggests that cytokine expression in some patients may be accelerated by either chemotherapy or ATRA. The implications of this observation for understanding the retinoic acid syndrome will require further studies.

Adolescent↗
PubMed2004

Safety and feasibility of an insulin adjustment protocol to maintain blood glucose concentrations within a narrow range in critically ill patients in an Australian level III adult intensive care unit.

OBJECTIVE: Recent data have shown a link between normal blood glucose levels and improved outcomes in intensive care patients. We wished to develop an insulin adjustment protocol for an adult intensive care unit to maintain blood glucose concentrations safely within a narrow range. METHODS: After a 6 month introductory period, an observational study was conducted during a 10 month period in an Australian level III intensive care unit to assess the safety and feasibility of an insulin adjustment protocol to maintain blood glucose concentrations safely within a narrow range. The protocol included a variable insulin infusion, a constant caloric source and frequent blood glucose level monitoring to detect and prevent hypoglycaemia. RESULTS: Over the 10 month period a total of 148 patients were studied using the protocol and represented 13 % of all intensive care unit admissions during this period. In total, there were 12,623 patient hours 'on protocol', with 5,603 blood glucose levels performed. The mean morning blood glucose level was 6.5 mmol/L and 49% of blood glucose levels were within the target range of 4.1 - 7.0 mmol/L. There were four recorded incidents of hypoglycaemia, defined as a blood glucose level of less than 2.2 mmol/L, the lowest at 1.5 mmol/L being the only symptomatic episode. The incidence of hyperglycaemia (blood glucose level > 10 mmol/L) was 13 % of all blood glucose level measurements. CONCLUSIONS: The insulin adjustment protocol with a constant caloric source and frequent blood glucose level monitoring was found to be safe and feasible in maintaining blood glucose concentrations within a narrow range in a mixed adult intensive care unit population.

Journal Article↗
PubMed2003

Comparison of temporal filtering methods for dynamic contrast MRI myocardial perfusion studies.

Dynamic contrast myocardial perfusion studies may benefit from methods that speed up the acquisition. Unaliasing by Fourier encoding the overlaps using the temporal dimension (UNFOLD), and a similar linear interpolation method have been shown to be effective at reducing the number of phase encodes needed for cardiac wall motion studies by using interleaved sampling and temporal filtering. Here such methods are evaluated in cardiac dynamic contrast studies, with particular regard to the effects of the choice of filter and the interframe motion. Four different filters were evaluated using a motion-free canine study. Full k-space was acquired and then downsampled to allow for a measure of truth. The different filters gave nearly equivalent images and quantitative flow estimates compared to full k-space. The effect of respiratory motion on these schemes was graphically depicted, and the performance of the four temporal filters was evaluated in seven human subjects with respiratory motion present. The four filters provided images of similar quality. However, none of the filters were effective at eliminating motion artifacts. Motion registration methods or motion-free acquisitions may be necessary to make these reduced FOV approaches clinically useful.

Algorithms↗