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Biomedical subjects

M Anthony

Publications and source records attributed to M Anthony.

At least 37 records · Page 2Linked to original sources

Platelet serotonin in patients with analgesic-induced headache.

The purpose of this study was to investigate the role of serotonin (5HT) in patients with analgesic-induced headache (AIH). We estimated platelet 5HT concentration in patients with AIH, migraine patients and non-headache controls, by using high performance liquid chromatography with electrochemical detection. Our results revealed a significant decrease (p < 0.001) in platelet 5HT content in patients with AIH as compared to migraine patients and non-headache controls (221.8 +/- 30.7, 445.3 +/- 37.4 and 467.2 +/- 38.5 ng/10(9) platelets, respectively). In contrast, a difference of lesser statistical significance (p = 0.022) was observed in platelet 5HT content after incubation with excess 5HT (1940.0 +/- 195.1, 2610.0 +/- 173.1 and 2560 +/- 165.2 ng/10(9) platelets for patients with AIH, migraine patients and non-headache controls, respectively). These data suggest that analgesic-induced suppression of 5HT uptake may interfere with the function of the pain modulatory system in the brainstem. Although the process by which analgesics interfere with this system is as yet unknown, it is possible that it may not be entirely due to defective 5HT uptake mechanisms.

Adult↗

Serotonin stimulates megakaryocytopoiesis via the 5-HT2 receptor.

It is known that platelet alpha-granule constituents including platelet-derived growth factor (PDGF), platelet factor 4 (PF4) and transforming growth factor-beta (TGF-beta) can affect megakaryocytopoiesis. Serotonin, a platelet dense granule constituent has been shown to have a mitogenic effect on fibroblasts and smooth muscle cells but whether it has the same effect on megakaryocytes remains unclear. In this study, we investigated the effect of serotonin on megakaryocytopoiesis and the possible mechanism of its effect using the mouse plasma clot culture method. The results show that: (a) serotonin significantly stimulates megakaryocyte colony formation with maximum stimulation at 100 nM; (b) enhanced action is found between serotonin and interleukin-3 (IL-3), interleukin-6 (IL-6), granulocyte macrophage-colony stimulating factor (GM-CSF), erythropoietin (EPO) and PDGF; (c) ketanserin, a 5-HT2 receptor antagonist, blocks the mitogenic effect of serotonin on megakaryocytopoiesis; and (d) Meg-01 cells (a megakaryocyte cell line) express 5-HT2 receptors. This study demonstrates that serotonin has a mitogenic effect on megakaryocytopoiesis and this effect may be mediated via the 5-HT2 receptor which is known to be coupled to G protein. It is suggested that serotonin may also be involved in the feedback control of megakaryocytopoiesis.

Animals↗

Serotonin uptake, storage and metabolism in megakaryoblasts.

Serotonin (5-hydroxytryptamine, 5-HT) uptake, storage and metabolism in human megakaryoblastic cell line (Meg-01) which acts as a model for megakaryocyte precursors, megakaryoblasts were investigated by using biochemical (HPLC) and morphological (electron microscope, EM) techniques. Results showed that Meg-01 cells were able to take up 5-HT. The intracellular 5-HT level was 2.8 +/- 0.4 and 51.8 +/- 4.9 (1 h) or 59.0 +/- 4.4 (2 h) ng/10(6) cells, before and after incubation with 5-HT, respectively, but no dense bodies were visualized after incubation with excess 5-HT by electron microscope observation. This uptake was inhibited by 28% on pre-incubation with fluoxetine and 60% of 5-HT in the cells was released on incubation with reserpine. 5-Hydroxyindoleacetic acid (5-HIAA) concentration of Meg-01 cells was increased after incubation of the cells with 5-HT (0 and 17.6 +/- 2.1 or 19.9 +/- 1.9 ng/10(6) cells, before and after incubation 1 or 2 h, respectively). The study suggests that: (1) 5-HT uptake ability is well established in megakaryocytes precursors, megakaryoblasts and the uptake ability is affected by reserpine and fluoxetine; (2) however, the capacity to store the amine is not well developed in megakaryoblasts and (3) megakaryoblasts may contain monoamine oxidase (MAO) which converts 5-HT to 5-HIAA.

Cells, Cultured↗

A proposal for a national mammography database: content, purpose, and value.

A national mammography database is a centralized, computerized method of data collection consisting of two possible parts: a national mammography audit and a system for monitoring and tracking patients. A national mammography audit refers to collecting and analyzing medical audit data of individual mammography practices at a national level and is a critical step in improving the interpretive component of mammography. The monitoring and tracking component refers to a centralized system that provides women and physicians with a recruitment and follow-up mechanism to optimize participation in mammography services. Both parts of a national mammography database represent important components in the improvement of mammography quality. However, unique scientific, legal, and fiscal concerns are important to consider before establishing a national mammography database.

Female↗

Controlling for confounding by indication for treatment. Are administrative data equivalent to clinical data?

There has been controversy about whether confounding by indication for treatment--that is, owing to physicians' conscious efforts to base treatment decisions on patients' pretreatment prognoses--makes nonrandomized, observational comparisons of treatments invalid. Some now believe evidence from studies of practice variation means that physicians' treatment decisions have little relationship to patients' prognostic clinical characteristics. They therefore believe that patients who receive different treatments should vary little in their baseline prognoses, and multivariable statistical methods should easily be able to adjust for any resultant confounding, even when analyses are restricted to administrative rather than clinical data. The objective of this study is to determine whether adjusting for variables found in administrative data sets produces the same results as does adjusting for clinical variables. Data were reanalyzed from a previously enrolled prospective sequential cohort of 227 hospitalized patients with suspected bacteremia who had blood cultures. The treatment under study was aminoglycoside therapy given empirically, that is, before blood culture results were known. The outcome of interest was death during hospitalization. Univariable analyses suggest that empiric aminoglycoside therapy had a positive association with mortality, by univarible logistic regression, odds ratio (OR = 3.1 (95% confidence interval = [1.6, 5.8]). Few administrative variables had univariable associations with aminoglycoside use or death. Multivariable analyses that controlled for them still suggest that aminoglycosides increased mortality; for example, in one model, adjusted OR = 3.2 (1.6, 6.5). Many clinical variables were strongly associated with aminoglycoside use or death. Analyses that controlled for them suggested that empiric aminoglycosides did not increase mortality; for example, in one model, adjusted OR = 1.2 (0.55, 2.7.) Results of adjustment for confounding using administrative data disagreed with the results of adjustment using clinical data. It is concluded that nonrandomized, observational outcome studies that fail to control for prognostic differences between patients receiving different treatments may not always be valid.

APACHE↗

Effects of ethanol, lovastatin and coenzyme Q10 treatment on antioxidants and TBA reactive material in liver of rats.

Alcohol metabolism may result in oxidant stress and free radical injury through a variety of mechanisms. Lovastatin may also produce oxidant stress by reducing levels of an endogenous antioxidant, coenzyme Q (CoQ). The separate and combined effects of ethanol, 20 EN% in a total liquid diet, and lovastatin, 67 mg/kg diet, on alpha-tocopherol, retinol palmitate, CoQ9 and thiobarbituric acid reactive (TBAR) material in liver from rats were determined. The effect of exogenous CoQ10 on these treatment groups was also determined. Food consumption, weight gain, liver lipid and TBAR material were similar between treatment groups. Compared to control animals, ethanol reduced retinol palmitate significantly, from 143 to 90 micrograms/g wet weight. Lovastatin had no effect on retinal palmitate nor did it act additively with ethanol. Ethanol decreased liver alpha-tocopherol from 28 to 12 micrograms/g wet weight and lovastatin diminished it to 12 micrograms; no additive effect was evident. Ethanol had no effect, but lovastatin decreased CoQ9 from 83 to 55 micrograms/g wet weight. Supplementation with CoQ10 did not modulate the effect of ethanol on retinal palmitate, but it did reverse the effect of lovastatin on CoQ9. Supplementary CoQ10 did not alter control levels of alpha-tocopherol, but it appeared to reverse most of the decrease in alpha-tocopherol attributable to ethanol or lovastatin separately. It only partially reversed the effect of ethanol and lovastatin combined on alpha-tocopherol, however. As expected, lovastatin had no effect on CoQ10 levels in supplemented animals. Ethanol, either separately or in combination with lovastatin, diminished liver stores of CoQ10 by almost 40%. We conclude that 20 EN% ethanol given in a liquid diet for 5 weeks is sufficient to lower retinol palmitate and that lovastatin reduces CoQ9. Both diminish alpha-tocopherol, an effect largely overcome by CoQ10 supplementation with either drug alone, but not with the combination. Since many individuals chronically consume the levels of ethanol represented by this experiment, and since a certain number of those also take lovastatin, further research into the possible clinical significance of these observations is warranted.

Animals↗

Simulated knee wear with cobalt chromium and oxidized zirconium knee femoral components.

A knee simulator that mimics the plowing/rolling wear mechanisms of the knee was used to compare wear properties of cobalt chromium and oxidized zirconium femoral components. The simulator flexes and extends the knee so that the femoral components travels from 0 degrees to 30 degrees while applying axial loads from 130 to 1300 lb. Three oxidized zirconium and 3 cobalt chromium femoral components were tested with 10-mm tibial polyethylene components. The oxidized zirconium femoral components caused significantly less ultra high molecular weight polyethylene wear than cobalt chromium femoral components. Tibial inserts that were articulated against the cobalt chromium components had evidence of scratching, burnishing, and delamination, but none of the surfaces that were articulated against oxidized zirconium components had evidence of delamination. Cobalt chromium surface roughness significantly increased during the 2,000,000 cycle test, but oxidized zirconium surface roughness was not affected. Polyethylene wear was correlated to a significant degree with the surface roughness of the femoral components. The improved wear characteristics of the ceramic articular surfaces can be explained by the wettability of the ceramic surface, which minimized adhesive wear, and the resistance of the hard, ceramic surface to roughening.

Chromium Alloys↗

The treatment of migraine--old methods, new ideas.

Most migrainous patients seeking medical attention suffer either from severe or frequent headaches and relief of pain is not sufficient treatment. Prevention of attacks is the aim of management in such patients. To be successful in this task, one needs to have some knowledge of headache mechanisms and a clear understanding of the mechanism of action of the drugs used for the purpose. This article tries to highlight knowledge in these two fields, so as to help the medical practitioner be successful in the treatment and prevention of migraine.

Humans↗

Headache and the greater occipital nerve.

This paper examines the clinical features of 500 patients with idiopathic headache. Of the 383 patients diagnosed as migraine, it was found that 184 (48%) were suffering from headaches due to irritation of the greater occipital nerve (GON). Such headaches could be arrested by injecting the ipsilateral greater occipital nerve (GON) with local anaesthetic, prevented for up to 4 weeks by injecting 'Depomedrol' into the region of the nerve and for several months by surgical division of the nerve. It is suggested that such patients are not suffering from typical migraine but from headaches due to neural irritation, which, for want of a better name, have been called 'occipital neuralgia'.

Adult↗

Oral sumatriptan in acute migraine.

The efficacy in acute migraine of oral sumatriptan was assessed in a double-blind, randomised, placebo-controlled, crossover study of 61 patients (mean age 39 [SD 10] years). 41 completed treatment of four attacks, two with sumatriptan 100 mg and two with placebo. The response rate (reduction in headache from moderate or severe to mild or absent at 2 h) was 51% (45/89) with sumatriptan and 10% (9/93) with placebo (p less than 0.01); rescue medication was needed at 2 h in 41% and 88%, respectively. Of 28 patients headache-free at 24 h, 11 (39%) had recurrent headache within 24 h. There were no substantial side-effects. Thus, sumatriptan is an effective well-tolerated treatment for acute migraine attacks.

Acute Disease↗

Effects of maternal calorie-restricted diet on development of the foetal heart, as evaluated in primary cultures of rat myocardial cells.

Very-low-calorie diets have been implicated in causing ventricular arrhythmias and sudden cardiac death. Furthermore, studies indicate that maternal carbohydrate-restricted diets consumed during pregnancy and lactation reduce foetal growth, parturition and postnatal survival of rat pups. In this study, Sprague-Dawley rats were maintained on a semi-purified full-calorie or 50% carbohydrate-calorie-restricted diet throughout pregnancy. The function and integrity of myocardial cell cultures obtained from 3-5-day-old offspring from both groups of dams were evaluated after a drug-induced toxic challenge. After the myocytes had been in culture for 4 days, they were exposed to various concentrations of amitriptyline (1 x 10(-3) to 1 x 10(-5) M). Morphology, beating activity, lactate dehydrogenase release, glucose utilization, beta-adrenergic receptor [125I]iodopindolol binding, and cellular adenosine triphosphate content were evaluated for 24 hr after drug exposure. There were no significant differences in morphology, beating activity or glucose utilization between the full-calorie and calorie-restricted groups. When compared with the full-calorie group, lactate dehydrogenase release from the calorie-restricted group was significantly lower at 8 hr for the untreated controls and those cells exposed to 1 x 10(-4) and 1 x 10(-5) M-amitriptyline. Adenosine triphosphate levels were lower in untreated controls from the calorie-restricted group when compared with the full-calorie group at 4 hr. Within the calorie-restricted group, those cultures exposed to 1 x 10(-4) M-amitriptyline had significantly depressed adenosine triphosphate levels after 8 hr of drug treatment when compared with their respective untreated controls. Finally, the calorie-restricted group had significantly increased binding affinities of beta-receptors. Thus, maternal consumption of calorie-restricted diets during pregnancy may affect the myocardial functional capacity and integrity of the offspring.

Adenosine Triphosphate↗

Isolation and characterization of simian immunodeficiency viruses from two subspecies of African green monkeys.

Cercopithecus aethiops (African Green monkey), a nonhuman primate species distributed throughout subsaharan Africa, has been shown to have high seroprevalence rates of antibodies to simian immunodeficiency virus (SIV), and therefore, has been proposed as a natural reservoir for immunodeficiency viruses. Our laboratories have isolated SIV-like viruses from two East African subspecies of C. aethiops designated grivet and vervet monkeys. Analysis of the structural proteins based on the molecular weights and immunologic cross-reactivity to the prototypic SIV(MAC), HIV-1, and HIV-2 isolates suggests that these viruses are distinctly different. Heterogeneity was observed in the molecular weights of the gag, pol, and env gene products between SIV isolates from vervets [SIV(AGM(VER))] and grivets [SIV(AGM(GRI))]. Phenotypically, SIV(AGM(VER)) isolates were distinguishable from SIV(AGM(GRI)) isolates by the apparent size difference of the major core antigen p24. All SIV(AGM(GRI)) and SIV(AGM(VER)) isolates were found to encode a transmembrane protein of approximately 40 kD (gp40) in contrast to gp32 of SIV(MAC). Furthermore, the transmembrane protein was shown to be encoded by the entire env open reading frame, unlike gp32 of SIC(MAC) or gp36 of SIV(AGM(TYO-1)). These data indicate that viruses from C. aethiops share common features with SIV(MAC) and HIV-1, but represent diverse SIV-like viruses which may vary according to subspecies and geographic location.

Amino Acid Sequence↗

Plasma serotonin in patients with chronic tension headaches.

Previous reports have suggested that platelet level of serotonin in chronic tension headache (CTH) is lower than in normal control subjects, and that there is continuous activation of platelets both in migraine and in CTH. In this study we compared platelet serotonin concentration in 95 patients with CTH, 166 patients with migraine and 35 normal control subjects. Mean platelet serotonin (ng/10(9) platelets) was 310 for the CTH group, 384 during migraine headache, 474 for normal control subjects and 514 in headache-free migrainous patients. There was significant statistical difference of values between CTH patients and those of normal control subjects as well as headache-free migrainous patients, but not of those of migrainous patients during headache. It is suggested that CTH is a low serotonin syndrome, representing one end of the spectrum of idiopathic headache, the other end being represented by migraine.

Adult↗