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PubMedDate not supplied

Positron emission tomography measurement of tumor metabolism and growth: its expanding role in oncology.

This work highlights the explosion and evolution of positron emission tomography (PET) for use in oncology research and clinical practice. 2-Deoxy-2-[F-18]fluoro-D-glucose (FDG)-PET is important in the staging of cancer, estimation of prognosis, and for its ability to predict therapeutic outcome. A number of new imaging agents are under development and may find a place in oncology when studies prove their utility. This scientific overview includes a review of the development of a number of thymidine analogs, such as 18F-3'-deoxy-3'-fluorothymidine (FLT) and 18F-1-(2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl)-thymine (FMAU), including chemical structure variations; their application in a variety of tumors; and the role of various kinetic models for understanding cellular proliferation. The greatest unmet need for PET is in further developing and validating its use in the measurement of treatment response.

Cell Proliferation↗
PubMed1997

Measurement and treatment of agitation following traumatic brain injury: II. A survey of the Brain Injury Special Interest Group of the American Academy of Physical Medicine and Rehabilitation.

OBJECTIVE: Determine national patterns of measuring and treating agitation after traumatic brain injury (TBI) by physiatrists with expressed interest in treating TBI survivors. DESIGN: A 70% random sample of members of the Brain Injury Special Interest Group of the American Academy of Physical Medicine and Rehabilitation was surveyed by telephone. MAIN OUTCOME MEASURE: The survey instrument was designed to determine the most common pharmacologic interventions for agitation and, where possible, match each drug with the target behavioral and cognitive characteristics for which it is prescribed. Data were also collected on the manner in which participants measured agitation and judged treatment efficacy. RESULTS: One hundred twenty-nine of 157 responded, yielding an 82% response rate. The majority of respondents were not measuring agitation in a standard fashion. The five most frequently prescribed drugs by the expert stratum were carbamazepine, tricyclic antidepressants (TCAs), trazodone, amantadine, and beta-blockers. In comparison, the nonexperts most often reported prescribing carbamazepine, beta-blockers, haloperidol, TCAs, and benzodiazepines. Desyrel (p = .06) and amantadine (p = .001) were significantly more likely to be chosen by experts than by nonexperts. Experts chose haloperidol significantly less often than nonexperts (p = .01). Prescription of sedating drugs such as haloperidol or benzodiazepines was not found to be associated with the acuity of injury of TBI patients in the respondent's practice, practice setting, or years of practice since completing residency. Choice of haloperidol to treat agitation was not significantly associated with the degree to which explosive anger, verbal aggression, or physical aggression were considered important to the respondent's definition of agitation. CONCLUSIONS: The majority of physiatrists surveyed did not formally measure agitation. Treatment strategies differ significantly between general physiatrists and those who specialize in the treatment of patients with TBI. The breadth of pharmacologic agents and strategies identified in this survey probably reflects the lack of research specific to the pathophysiology of the disorder of posttraumatic agitation.

Adult↗
PubMed2003

Prevention and suppression of metal packing fires.

Structured packing has been widely used because of large surface area that makes possible columns with high capacity and efficiency. The large surface area also contributes to fire hazards because of hydrocarbon deposits that can easily combust and promote combustion of the thin metal packing materials. Materials of high surface area that can fuel fires include reactive metals, such as titanium, and materials that are not considered combustible, such as stainless steel. Column design and material selection for packing construction is discussed together with employee training and practices for safe column maintenance and operations. Presented also are methods and agents for suppression of metal fires. Guidance for prevention and suppression of metal fires is related to incidents involving packing fires in columns.

Explosions↗
PubMed2002

Bipolar disorders and the effectiveness of novel anticonvulsants.

The discovery that valproic acid is helpful in the management of patients with rapid-cycling bipolar disorder led to an explosion of research culminating in the third-generation anticonvulsants. Refractory depressive phases are frequent in bipolar disorders. No studies to date have shown that gabapentin is effective in bipolar mania or hypomania. Lamotrigine may have a role in treating bipolar depressive episodes, but it is not a particularly effective antimanic agent. Topiramate has shown encouraging results in both depressed and manic bipolar patients, and it may also promote weight loss. The new anticonvulsants are promising agents for the treatment of bipolar disorders, but they are heterogeneous with regard to their efficacy, target symptoms, and adverse event profiles.

Acetates↗
PubMed1997

The explosion of morbidity and mortality trials in hypertension.

The highlights of each generation of hypertension trials have been varied, but interrelated. The initial hypertension trials focused on middle-aged hypertensive individuals and later on the elderly, with emphasis on diastolic blood pressure and subsequently on systolic blood pressure. Past generations of trials elucidated whether and whom to treat. The current explosion of morbidity and mortality trials in hypertension largely seeks to learn what drugs should be used and to delineate what blood pressure goals should be targeted.

Aged↗
PubMed2001

Hematotoxicity induced by paclitaxel: in vitro and in vivo assays during normal murine hematopoietic recovery.

Paclitaxel is a drug widely used in several oncological trials. Like other antineoplastics, it causes severe neutropenia. However, its effects on erythropoiesis are not as well known. This study analyzes the recovery of normal murine hematopoiesis after single dose paclitaxel administration (29 mg/kg i.p.) over 20 days. Different assays were used to analyze the restorative kinetics from primitive early progenitors to mature functional erythroid cells. Proliferation of the erythroid compartment was assessed by DNA microculture assays in medullar and splenic cells stimulated with recombinant human erythropoietin (rh Epo 0-500 mU/ml). Enhancement of early hematopoietic progenitors was determined using clonogenic assays and erythroid terminal maturation by 59Fe incorporation. Peripheral hematologic parameters and cellularities in both tissues were also determined on each day of the experimental schedule. At 2 days post-paclitaxel treatment, medullar cellularity diminished drastically (> 90%) and 59Fe incorporation decreased in all compartments. DNA assay revealed maximum sensitivity to Epo (p < 0.05 with 15 mU/ml) while clonogenic cultures failed to show significant results. At 5 days both bone marrow and spleen semisolid cultures showed great expansion of early hematopoietic progenitors (about 5- and 83-fold. respectively). Hormonal sensitivity decreased progressively along the experiment. Splenic cultures showed a linear dose-response to rh Epo at day 5 post-paclitaxel administration (p < 0.05 with 125 mU/ml). Medullar and splenic total progenitor colony-forming units (CFU) scorings with and without rh Epo revealed a notable enhancement at 5 days post-paclitaxel treatment. Data from this study suggest that paclitaxel causes deep injury in the erythropoietic compartment, including temporary variations of Epo sensitivity in late bone marrow erythroid progenitors, early multilineage hematopoietic explosion and terminal erythroid precursors depletion as a result of a complex microenvironmental restitutive regulation.

Animals↗
PubMed1979

Prophylactic drugs in the management of childhood asthma.

Recurrences of explosive, severe asthma in children can often be prevented by immunotherapy and constant surveillance of environmental and dietary control. In addition, judicious and preserving use of pharmaceuticals may be employed for prophylaxis in childhood asthma. These include cromolyn sodium by inhalation, beclomethasone dipropionate aerosols, round-the-clock methylxanthines and beta 2 adrenergic bronchodilator agents. Their application is discussed.

Adolescent↗
PubMed1992

Molecular biology of serotonin receptors.

The past decade has seen an explosive growth in our understanding of neurotransmitter receptors and the roles they play in neurotransmission. This is particularly true of the serotonin receptors where a synergy of basic science and clinical research has not only produced a deeper understanding of serotonin receptors and their actions but also resulted in the availability of new therapeutic agents useful for treating a number of psychiatric illnesses. This chapter details our current knowledge of the major subtypes of the serotonin receptor, including recent advances in the molecular biology, pharmacology, biochemistry, and clinical correlates of these receptors.

Anxiety Disorders↗
PubMed2004

Magnesium in clinical medicine.

Until recently the physiological role of magnesium was essentially ignored. However, with the development of new technologies to measure the intracellular free concentration of magnesium ([Mg2+]i), the biologically important fraction, there has been an explosion of interest in the molecular, biochemical, physiological and pharmacological functions of magnesium. In addition improved methods for assessing magnesium status in the clinic have contributed to the further understanding of magnesium regulation in health and disease. Magnesium deficiency is now considered to contribute to many diseases and the role for magnesium as a therapeutic agent is being tested in numerous large clinical trials. This review focuses on clinical manifestations associated with magnesium deficiency and highlights the clinical significance of hypermagnesemia. Specific clinical conditions in which magnesium deficiency has been implicated to play a pathophysiological role, namely hypertension, ischemic heart disease, arrhythmias, prec-eclampsia, asthma and critical illness will be discussed and the possible therapeutic role of magnesium will be considered. Although there is still much to be learnt regarding the exact role of magnesium in clinical medicine, there are two conditions where magnesium is now considered the therapeutic agent of choice, pre-eclampsia and torsades de pointes. Future research, both at the fundamental and clinical levels, will certainly facilitate our understanding of how magnesium contributes to pathological processes and under what circumstances it should be used therapeutically.

Cardiovascular Diseases↗
PubMed2001

[The new antiendotoxin strategies].

Lipopolysaccharide(LPS) is important in the pathogenesis of sepsis infected by gram-negative bacteria in humans, and part or all of this pathophysiology is mediated by a complex secondary inflammatory response. Administration of purified LPS or a variety of LPS-free recombinant mediators can reproduce much of the pathophysiology of gram-negative sepsis. There has been an explosion of new information over the last several years regarding the interactions of LPS with proteins and cells. Blocking sepsis at the bacterial toxin level is appealing because it is upstream, so that the secondary pathologic inflammatory cascade may be limited or prevented. A variety of antiendotoxin strategies have been proposed. Therapies under investigation include agents that bind and neutralize LPS, agents or systems that enhance LPS clearance, and agents that inhibit LPS interaction with serum elements or cellular receptors.

Acute-Phase Proteins↗
PubMed1991

Importance of experimental models for the development of clinical trials on thromboatherosclerosis.

Experimental models of vascular injury have enhanced our understanding of the pathophysiological process leading to vascular obstruction in both spontaneous and accelerated atherosclerosis. Based on experimental findings, we present and discuss a pathological classification of vascular injury or damage and its role in the pathogenesis of various vascular diseases. In addition, these animal models have provided insights into the roles of platelets and lipid metabolism in the evolution and progression of atherosclerosis and have suggested potential therapeutic applications. Thus, based on studies in the pig models, antiplatelet agents have been shown for the first time to have a beneficial effect in preventing the formation and progression of coronary atherosclerotic lesions in humans. Similarly, our findings in high density lipoprotein plasma fractions regarding inhibition and even reversal of the process of atherosclerosis in a hypercholesterolemic rabbit model have added new insights to an explosive field of lipoprotein research and provided new avenues of therapeutic strategies. our in vivo and ex vivo pig models of an extracorporeal perfusion chamber mimicking the various coronary conditions have aided in the understanding of the pathophysiology of the acute coronary syndromes and intensified our search for the ideal antithrombotic regimen in these high-risk patients. Finally, a carotid pig model of balloon angioplasty, a dog model of saphenous vein grafting, and a pig model of heart transplantation not only have provided insights into the pathophysiological process of accelerated atherosclerosis but also are allowing development of new antithrombotic and antiproliferative approaches for the prevention of these accelerated vascular diseases. In summary, we are entering an exciting era in vascular research. Significant advances in our understanding of vascular injury or damage as well as the interactions of blood cells and lipids with the vascular wall have allowed us to formulate new experimental strategies with subsequent clinical application in the prevention and progression of these vascular diseases.

Animals↗
PubMed1966

U-21,963, a new antibiotic. II. Isolation and characterization.

The isolation and characterization of antibiotic U-21,963 are discussed. This compound is a highly unsaturated monobasic acid with the molecular formula C(9)H(7)NO(3). The molecular weight is 177. It is dextrorotatory, [alpha](D) = +138 degrees , and has a pK(a) of 5.1. The ultraviolet absorption spectrum, which showed a maximum at 223 mmu (epsilon = 15,115), indicates unsaturation alpha-beta to the carboxyl group, and the infrared spectrum suggests the presence of an acetylenic group. Explosive decomposition of U-21,963 at 97 C conforms with the latter. U-21,963 is relatively insoluble in water, but readily soluble in ethyl alcohol, acetone, and halogenated hydrocarbons.

Anti-Bacterial Agents↗
PubMed2006

Inflammatory bowel diseases.

The inflammatory bowel diseases remain at the forefront of clinical investigation. Immunologic and genetic advances are fueling an explosion of novel diagnostic and therapeutic modalities. With further breakthroughs, there is hope that in the near future, these illnesses will no longer be considered either idiopathic or chronic.

Adult↗
PubMed1991

[Turnover of central nervous system stimulating drugs in Norway during the period 1980-1989].

Statistics from the Norwegian Medicinal Depot (Norsk Medisinaldepot) show that sales of methylphenidate in Norway increased by approximately 300% from 1985 to 1989. The Norwegian Ministry of Health and Social Affairs (Directorate of Health) has approved only one indication for the use of stimulants in child and adolescent psychiatry, namely the hyperkinetic syndrome. The author discusses the explosive use of stimulant drugs and presents several interpretations. It is concluded that the indications for use of these drugs in child and adolescent psychiatry should be discussed and clarified.

Amphetamine↗
PubMed1994

Efficacy of carbamazepine compared with other agents: a clinical practice survey.

BACKGROUND: To gain an impression of the experience with and efficacy of carbamazepine relative to other agents and relative to its use in treating psychiatric and neurologic disorders in general clinical practice, a survey was distributed in 1988 to psychiatrists practicing in the United States. METHOD: The survey was mailed to 9030 members of the American Psychiatric Association (APA) who had expressed an interest in the study and treatment of affective disorders in a 1982 APA survey. The survey sampled clinicians' experience of the efficacy and side effects of carbamazepine in a number of psychiatric and neurologic conditions. Each clinician also provided global impression ratings of the efficacy of a variety of traditional and novel treatments. RESULTS: Completed surveys were returned by 2543 (28%) physicians. Carbamazepine was reported to be moderately to markedly effective in the following percentage of patients: partial complex seizures, 85.2%; generalized seizures, 82.9%; trigeminal neuralgia, 81.5%; mania prophylaxis, 72.9%; acute bipolar depression, 67.5%; intermittent explosive disorder, 65.2%; acute mania, 62.2%; schizoaffective disorder, 58.8%; other pain syndromes, 51.2%; posttraumatic stress disorder, 48.1%; borderline personality disorder, 43.0%; unipolar depression, 32.2%; schizophrenia, 25.7%; and alcohol withdrawal, 15.9%. About 4.4% of the patients reported were withdrawn from carbamazepine because of side effects. CONCLUSION: Carbamazepine was widely used to treat a variety of psychiatric conditions in 1988 and found to be of use in the acute and long-term treatment of bipolar illness. It was rated slightly less effective than lithium, electroconvulsive therapy, or neuroleptics, but more effective than several other agents. The results of the survey highlight many areas in need of further systematic investigation.

Attitude of Health Personnel↗
PubMedDate not supplied

Report from the society for biological therapy and vascular biology faculty of the NCI workshop on angiogenesis monitoring.

The field of tumor angiogenesis has seen explosive growth over the last 5 years. Preclinical as well as early clinical evaluation of novel compounds is progressing at a rapid pace. To gain a perspective on the field and to take stock of advances in the understanding of molecular mechanisms underlying the process of tumor angiogenesis as well as ways of monitoring the activity of agents, the Society for Biologic Therapy and the National Cancer Institute's Vascular Biology Faculty convened a Workshop on Angiogenesis Monitoring in November 2002. The Workshop was composed of invited speakers and participants from academia, industry, and government. It was divided into 3 sessions, each chaired by leaders in the field. The first focused on advances in the understanding of the cellular and molecular mechanisms of angiogenesis in tumors. The second examined preclinical assay systems that are useful in vascular biology. The third addressed the translation to the clinic and monitoring of antiangiogenic activity of agents in patients and novel trial designs. What follows is a summary of the discussions and findings of each session.

Animals↗
PubMed2006

Kinetics of human serum butyrylcholinesterase and its inhibition by a novel experimental Alzheimer therapeutic, bisnorcymserine.

An explosion in the incidence of neurodegenerative diseases, particularly Alzheimer's disease (AD), is predicted in coming decades. Hence, the need to devise and assess new treatment strategies has never been more acute. AD, although an irreversible and progressive disorder, is currently treated with palliative, symptomatic therapy: primarily with acetylcholinesterase (AChE) inhibitors to amplify remaining cholinergic activity. New agents that, additionally, affect disease progression are sorely needed. Inhibition of brain butyrylcholinesterase (BuChE) represents a new drug target for AD treatment. Therefore, hand-in-hand with the development of selective ligands to inhibit BuChE in brain, it is fundamental to optimize assay conditions for kinetic studies of human BuChE. Kinetic analysis of serum BuChE, which is structurally similar to brain enzyme, was performed at dual substrate (butyrylthiocholine iodide) concentration ranges: 3-80 microM (low) and 25-800 microM (optimal) by use of the Ellman technique. Interaction of BuChE with a novel experimental AD therapeutic, bisnorcymserine (BNC; 0.06-2.0 nM) was also studied ex vivo. The IC_{50} and other key kinetic constants were determined for human serum BuChE inhibition by BNC, which proved to be a highly potent inhibitor in comparison to its structural analogue, cymserine. BNC may, additionally, lower the amyloid plaque-associated protein, amyloid-beta peptide. In synopsis, the characterization of the kinetic parameters of BuChE and BNC, described herein, is both aiding in the design of novel agents and optimizing their translation toward clinical use.

Alzheimer Disease↗
PubMedDate not supplied

Hazardous substances releases causing fatalities and/or people transported to hospitals: rural/agricultural vs. other areas.

INTRODUCTION: Mass-casualty and hospital preparedness has been analyzed widely. However, information regarding the types of areas where these events occur is limited. Therefore, the characteristics of acute hazardous substances releases resulting in death/multiple-victim events occuring in rural/agricultural areas and in all other areas were studied and compared. METHODS: Data reported to the Hazardous Substances Emergency Events Surveillance (HSEES) system from 16 state health departments during 1993-2000 were used to examine factors associated with events with death/multiple victims involving acute release of hazardous substances. A death/multiple-victim event is defined as any event resulting in a death and/or at least five people being transported to a hospital. RESULTS: Of a total of 43,133 events, 6661 occurred in rural/agricultural areas. Of these, 107 were death/multiple-victim events with 632 victims, of whom 91 died and 77 were hospitalized. All other areas had 472 death/multiple-victim events with 7981 victims, of whom 116 died and 413 were hospitalized. Death/multiple-victim events in rural/agricultural areas were more likely to be associated with transportation (Proportional Ratio (PR) = 4.1, 95% CI = 3.1-5.4) and fires and/or explosions (PR = 1.4, 95% CI = 0.95-2.0) than were death/multiple-victim events in all other areas. Among transportation-related events in rural/agricultural areas, 19 were associated with air transport--mainly crop dusters--and resulted in 18 deaths. Responders were three times more likely to be injured in rural/agricultural areas. Of responders, volunteer firefighters constituted 52% compared with 6.7% in all other areas. The most frequently released chemicals in rural/agricultural areas were ammonia, chlorine, and pesticides. In all other areas, ammonia, chlorine, hydrochloric acid, carbon monoxide, and 0-chlorobenzylidene malononitrile, a tearing agent often associated with an illegal or unauthorized act, were released most frequently. CONCLUSIONS: Findings from this analysis suggest that remedial actions should address safety measures in both transportation and fixed facilities containing acute hazardous substances. These include regular maintenance of equipment, education of workers about the substances used in their facility, rigorous training and licensing of drivers and crop duster operators, and education and training of employees and first responders in the use of protective equipment. These activities may reduce the number of events, casualties, and costs associated with hazardous substance events.

Agriculture↗