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Biomedical subjects

G Martin

Publications and source records attributed to G Martin.

At least 55 records · Page 3Linked to original sources

EXAFS determination of the size of Co clusters on silica.

The metallic Co catalyst for the Fischer-Tropsch reaction is prepared by reduction of Co salts impregnating microporous silica. The average size of the metallic Co clusters is determined from the average number of neighbours deduced from Co K-edge EXAFS of catalyst samples. A model EXAFS signal constructed from the scattering paths of Co metal fcc lattice with lengths up to 5 A is calibrated on a reference spectrum of Co metal foil. Catalyst spectra are interpreted with the same model expanded with variable neighbour fractions of the four nearest shells. Cluster size is obtained from comparison with the neighbour-fractions of consecutive fcc magic-number clusters.

Journal Article↗

Activation of the phosphatidylinositol 3-kinase/Akt pathway protects against interleukin-3 starvation but not DNA damage-induced apoptosis.

Baf-3 cells are dependent on interleukin-3 (IL-3) for their survival and proliferation in culture. To identify anti-apoptotic pathways, we performed a retroviral-insertion mutagenesis on Baf-3 cells and selected mutants that have acquired a long term survival capacity. The phenotype of one mutant, which does not overexpress bcl-x and proliferates in the absence of IL-3, is described. We show that, in this mutant, Akt is constitutively activated leading to FKHRL1 phosphorylation and constitutive glycolytic activity. This pathway is necessary for the mutant to survive following IL-3 starvation but is not sufficient or necessary to protect cells from DNA damage-induced cell death. Indeed, inhibition of the phosphatidylinositol 3-kinase (PI3K)/Akt pathway in Baf-3 cells does not prevent the ability of IL-3 to protect cells against gamma-irradiation-induced DNA damage. This protective effect of IL-3 rather correlates with the expression of the anti-apoptotic Bcl-x protein. Taken together, these data demonstrate that the PI3K/Akt pathway is sufficient to protect cells from growth factor starvation-induced apoptosis but is not required for IL-3 inhibition of DNA damage-induced cell death.

Animals↗

Making a vertebrate limb: new players enter from the wings.

What initiates vertebrate limb development and induces limbs to form where they do? For several years the answer to this intriguing question has been framed in terms of a working model that limb induction depends on a dialogue between two members of the Fibroblast Growth Factor (FGF) family of intercellular signaling molecules, FGF8 and FGF10. Now, a recent paper has written roles for signals encoded by WNT genes, the vertebrate relatives of the Drosophila wingless gene, into the script.

Animals↗

International prospective evaluation of scintimammography with technetium-99m sestamibi: interim results.

OBJECTIVE: The purpose of this study is to evaluate the validity and reliability of scintimammography with technetium-99m (99mTc)-labeled sestamibi as an adjunct radiodiagnostic agent in the diagnosis of breast cancer. METHODS: This is a multicenter prospective cohort clinical trial that was initiated in June 1999 and will terminate May 2001. All patients with a physical or mammographic finding visiting any of the participating clinics are enrolled in the study. Patients who are younger than 18 years, pregnant, not willing to sign the consent form, or who have undergone an invasive procedure on the breast 30 days or less before scintimammography are excluded. At the time of the first interim report, 633 patients had been recruited from six Canadian centers. To date complete data have been collected for 530 patients. RESULTS: The mean (SD) age of the patients is 56 (12) years with a range between 24 and 85. There were 122 (23%) of the women in the sample who were postmenopausal and 36 (7%) who were perimenopausal. Breast density was graded as dense for 127 (24%), normal for 260 (50%), and fatty for 138 (26%). Of the 530 women in the study 156 (29%) had a palpable mass at physical examination. The mammographic results were classified as 76 (14%) breast imaging reporting and data system (BIRADS) 5, 60 (11%) BIRADS 4, 70 (13%) BIRADS 3 and the remaining BIRADS 2 or 1. The scintimammography results were positive for 118 (23%) of the patients and negative for 412 (78%). The histopathology showed malignant breast disease for 66 (12.5%) of the patients in the sample. Sensitivity and specificity of scintimammography for the detection of breast cancer was estimated 90.9% and 87.5%, respectively. A positive predictive value (PPV) of 50.8% with a negative predictive value of 98.5% and an accuracy of 87.5% were calculated. The PPV is interpreted as the posttest probability of disease given a positive test result. In this sample the pretest probability of disease would be best estimated by the prevalence of disease, which is equal to 12.5%. A positive scintimammography result would change the estimated probability to 51%, which is equivalent to a 400% change from the pretest value. Therefore a positive scintimammography result significantly increases our ability to predict the presence of malignant disease in this population. CONCLUSION: The interim results of the present study suggest that scintimammography with 99mTc-sestamibi is accurate and potentially useful as an adjunct to mammography for the detection of breast cancer.

Adult↗

Nonlinear mill control.

A mill is a mechanical device that grinds mined or processed material into small particles. The process is known to display significant deadtime, and, more notably, severe nonlinear behavior. Over the past 25 years attempts at continuous mill control have met varying degrees of failure, mainly due to model mismatch caused by changes in the mill process gains. This paper describes an on-line control application on a closed-circuit cement mill that uses nonlinear model predictive control technology. The nonlinear gains for the control model are calculated on-line from a neural network model of the process.

Algorithms↗

Sequential therapy in advanced non-small-cell lung cancer with weekly paclitaxel followed by cisplatin-gemcitabine-vinorelbine. A phase II study.

OBJECTIVES: New effective therapies are needed to improve the outcome of patients with advanced non-small-cell lung cancer (NSCLC). The aim of this study was to assess the response rate and survival obtained with a sequential regimen of chemotherapy. PATIENTS AND METHODS: Patients with newly diagnosed stage IIIb-IV NSCLC were included. They all had measurable disease and a good performance status (0-2 in the Eastern Cooperative Oncology Group scale). Chemotherapy consisted of weekly paclitaxel 150 mg/m2 x 6, followed two weeks later by cisplatin 100 mg/m2 on day 1, gemcitabine 1,000 mg/m2 on days 1 and 14, and vinorelbine 25 mg/m2 on days 1 and 14 (CGV). CGV was administered every 28 days for a maximum of six courses. RESULTS: Fifty-two patients were included, 19 (37%) with stage IIIb and 33 (63%) with stage IV disease. After therapy with weekly paclitaxel. 29 partial responses were obtained (56%, 95% confidence interval (95% CI): 38%-67%), whereas 15 patients had stable disease (29%) and eight had a progression (15%). After CGV, there were four complete remissions (8%) and 24 partial responses (46%), for an overall response rate of 54% (95% CI: 37%-65%). Eight patients had stable disease (15%) and 16 had a progression (31%). No patient progressing after paclitaxel responded to CGV, whereas 5 out of 15 patients with stable disease reached a partial response with CGV (33%). On the contrary, 5 out of 29 patients with a partial response to paclitaxel progressed after CGV (17%). Median survival has not been reached after a median follow-up of 14 months. Median time to progression was nine months. Fifty-six percent of patients remain alive at one year. Two hundred eighty-nine courses of paclitaxel and 170 of CGV were given, with a median of 5.5 and 3.4 per patient, respectively (ranges 2-6 and 0-6. respectively). WHO grade 3-4 toxicities for paclitaxel were: neutropenia in two patients (4/) and peripheral neuropathy in five (10%). Two patients had allergic reactions requiring paclitaxel withdrawal, whereas four (8%) had hyperglycemia >250 mg/ml. Grade 3-4 toxicities for CGV were: neutropenia in ten patients (20%), peripheral neuropathy in six (12%), anemia in four (8%), nausea/vomiting in five (10%). thrombocytopenia in two (4%), and fatigue in four (8%). CONCLUSION: Our results suggest that sequential chemotherapy with weekly paclitaxel followed by CGV is highly active in patients with advanced NSCLC and has an acceptable toxicity. This schedule deserves further evaluation in a phase III study.

Adult↗

Gender differences in the relationship between depression and suicidal ideation in young adolescents.

OBJECTIVE: This study examined the risk relationship between depressive symptomatology and suicidal ideation for young adolescent males and females. METHOD: A large cohort of students in their first year of high school completed the Center for Epidemiological Studies Depression Scale (CES-D) and the Adolescent Suicide Questionnaire. The risk relationship between depressive symptomatology and suicidal ideation was modelled using non-parametric kernel-smoothing techniques. RESULTS: Suicidal ideation was more frequently reported by females compared with males which was partly explained by females having higher mean depression scores. At moderate levels of depression females also had a significantly higher risk of suicidal ideation compared with males and this increased risk contributed to the overall higher levels of female ideation. CONCLUSIONS: The risk relationship between depressive symptomatology and suicidal ideation is different for young adolescent males and females. The results indicate that moderate levels of depressive symptomatology can be associated with suicidal ideation (especially among young females) and that for these young people a suicide risk assessment is required.

Adolescent↗

The death of Henry II of France: a sporting death and post-mortem.

In 1559 Henry II King of France was wounded in a tournament and died. A broken lance entered his right orbit, destroying his eye and leaving behind many splinters. The skull was not penetrated but infection spread intracranially. Both Ambroise Paré and Vesalius saw him and predicted death. Nine days after wounding, both attended the King's post-mortem. The story shows how difficult life was without antisepsis, anaesthesia, antibiotics or investigations. The King's stubbornness highlights the dangers of continuing to play after concussion.

Athletic Injuries↗

Systemic GLP-2 levels do not limit adaptation after distal intestinal resection.

BACKGROUND/PURPOSE: Glucagonlike peptide 2 (GLP-2) is trophic for the small bowel; it is produced by L cells in the distal intestine in response to luminal nutrients. This study tests the hypothesis that distal small bowel and cecal resection would decrease GLP-2 levels and reduce adaptation. METHODS: Male Sprague-Dawley rats (200 to 300 g) underwent either ileal transection (controls) or resection of the ileum and cecum, leaving 10 or 20 cm jejunal remnant anastomosed to the ascending colon. Animals were followed up for up to 21 days. Endpoints were daily weights, intestinal histology, in vivo absorption of 3-0 methylglucose (a measurement of active nutrient absorptive capacity), and serum GLP-2 levels. RESULTS: The control group had a maximum 6% weight loss around day 2, and then recovered with a steady weight gain. The 10-cm jejunal remnant group lost weight continuously and never recovered postsurgery. The 20-cm jejunal remnant group of animals had a maximum of 12% weight loss by day 4 and then slowly gained weight. The average villus height increased significantly (P <.01) in the 10-cm and 20-cm jejunal remnant groups compared with controls. Absorption of 3-0 methylglucose was significantly decreased (P <.01) in both resected groups. Serum GLP-2 levels were increased significantly (P <.05) when compared with controls in both resection groups. CONCLUSIONS: Increased serum GLP-2 levels were found in the ileocecal resection rat model, and these levels correlated with morphologic adaptation. However, this morphologic adaptation was not sufficient to restore nutrient absorption as shown by weight changes and 3-0 methylglucose absorption. Thus, the original hypothesis of this study is incorrect: systemic GLP-2 levels do not limit adaptation following distal ileocecal resection.

3-O-Methylglucose↗

Did Pope Boniface die of a subdural?

At the age of 68, Pope Boniface the VIII was hit in the face with a heavy mailed fist and then imprisoned, where he neither ate nor drank for 48 hours. Rescued, he was alert and rational but a few days later unable to appear in public. In Italy he is sa id to have died of shame at being hit. He died 5 weeks after the blow, probably with alternating periods of drowsiness and delirium. It is suggested he died of a subdural haematoma.

Aged↗

Angiotensin AT1 receptor antagonist irbesartan decreases lesion size, chemokine expression, and macrophage accumulation in apolipoprotein E-deficient mice.

Recent data suggest that angiotensin II AT1 receptor antagonists may be beneficial in the treatment of atherosclerosis. To clarify how AT1 receptor antagonists reduce atherosclerosis, the effect of irbesartan on atherosclerotic lesion development was determined in low-fat, chow-fed apolipoprotein (Apo) E-deficient mice. Irbesartan (50 mg/kg per day) strongly decreased lesion development after a 12-week treatment period (lesion size: irbesartan treated, 20,524 +/- 4,200 microm(2) vs. control, 99,600 +/- 14,500; 79.4% inhibition, p < 0.001). This effect was not due to an effect of irbesartan on lipoprotein levels because irbesartan slightly increased total cholesterol levels and decreased the ratio of Apo A-I relative to Apo B levels. Immunochemical analysis of the atherosclerotic lesions using the mac3 monoclonal antibody showed the presence of macrophages in the lesions of control mice, whereas sections from irbesartan-treated animals only showed occasional labeling in the lesion area. These data suggest that irbesartan inhibits monocyte/macrophage influx into the vessel wall. Therefore, expression levels of monocyte chemoattractant protein-1 (MCP-1), as well as other chemokines involved in macrophage infiltration into the lesion area, were measured in the aortic sinus of control and irbesartan-treated animals. Irbesartan treatment strongly decreased MCP-1 mRNA levels as well as MCP-1 immunostaining in the lesion area. This effect of irbesartan on MCP-1 occurred without an effect on CCR2, the receptor of MCP-1. Expression of macrophage inflammatory protein (MIP)-1alpha, another CC chemokine expressed in atherosclerotic lesions, was also reduced after irbesartan treatment, without effect on CCR3 and CCR5, the receptors of MIP-1alpha. Concomitantly, the expression of the angiogenic chemokines KC and MIP-2, which are functionally related to interleukin-8, were downregulated, whereas their shared receptor CXCR2 was upregulated. These data suggest that inhibition of the inflammatory component of lesion progression plays an important role in the inhibitory effect of AT1 receptor antagonists on atherosclerotic lesion formation.

Angiotensin Receptor Antagonists↗

Influence of metal thickness on phase velocity and thermal sensitivity of SAW devices.

Most surface acoustic wave (SAW) devices exhibit a very small sensitivity to thermal effects. However, even on intrinsically compensated crystal cuts, the deposition of metal strips at the surface (transducers or reflectors) induces important changes in the thermoelastic properties of the device. A theoretical approach based on the Sinha-Tiersten perturbation method is proposed to model the influence of metallization on SAW properties on (ST, X) quartz, namely the temperature stability of the phase velocity of Rayleigh waves. Because this perturbation method only gives access to the first-order temperature coefficient of frequency (TCF), it is combined with a conventional calculation of the second-order TCF to predict the evolution of the turnover temperature. The proposed calculation also requires temperature derivatives of the elastic constants of the metal, which can be calculated for different materials. Finally, theoretical results are compared with experimental data measured on SAW devices on (ST, X) quartz using aluminum gratings.

Journal Article↗

Statin-induced inhibition of the Rho-signaling pathway activates PPARalpha and induces HDL apoA-I.

Statins are inhibitors of the rate-limiting enzyme in cholesterol synthesis, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase. In addition to reducing LDL cholesterol, statin treatment increases the levels of the antiatherogenic HDL and its major apolipoprotein apoA-I. Here, we investigated the molecular mechanisms of apoA-I regulation by statins. Treatment with statins increased apoA-I mRNA levels in human HepG2 hepatoma cells, and this effect was reversed by the addition of mevalonate, implicating HMG-CoA reductase as the relevant target of these drugs. Pretreatment with Actinomycin D abolished the increase of apoA-I mRNA, indicating that statins act at the transcriptional level. Indeed, statins increased the human apoA-I promoter activity in transfected cells, and we have identified a statin response element that coincides with a PPARalpha response element known to confer fibrate responsiveness to this gene. The statin effect could be abolished not only by mevalonate, but also by geranylgeranyl pyrophosphate, whereas inhibition of geranylgeranyl transferase activity or treatment with an inhibitor of the Rho GTP-binding protein family increased PPARalpha activity. Using dominant negative forms of these proteins, we found that Rho A itself mediates this response. Because cotreatment with statins and fibrates activated PPARalpha in a synergistic manner, these observations provide a molecular basis for combination treatment with statins and fibrates in coronary heart disease.

Animals↗

Educating parents about youth suicide: knowledge, response to suicidal statements, attitudes, and intention to help.

This study evaluated the video Youth Suicide: Recognising the Signs as a parent educational medium. Before and after viewing the video, parents (N = 112) of young people answered questionnaires measuring their (1) knowledge of suicidal signs, (2) responses to a young person showing suicidal signs, (3) attitude to suicide, and (4) intentionalitv toward suicidal people. After the video, parents' knowledge of suicidal signs, responses toward a suicidal person, and intention to help improved. Their attitude was more rejecting of suicide. Knowledge and intentionality predicted response to suicidal statements, but no relationships existed between attitude and the other variables. Implications for youth suicide education programs are discussed.

Adult↗

Youth suicide issues in general practice.

OBJECTIVE: To identify the factors that predispose to suicidal thinking and behaviours in young Australians who visit a general practitioner. METHOD: A clinical audit program that required a pre-entry survey of 50 young people attending a GP. RESULTS: Suicidal thinking and behaviours in young people have been increasing over the past decades. In this survey of over 6000 young Australians, evidence suggests that there are fundamental mental health factors that all GPs should explore with young people to assess the risk of self harm. These include feelings of hopelessness and powerlessness, the pattern and type of drug use, a history of sexual abuse, concerns about sexuality and sexual identity. DISCUSSION: General practitioners should not rely on their previous knowledge of a young person but continue to explore issues of suicide where any combinations of the above factors are present.

Adolescent↗