Ten years of chlorpromazine.
Explore the source record for details and available documents.
Chlorpromazine↗
Biomedical subjects
M Hamilton
Publications and source records attributed to M Hamilton.
The prevalence and patterns of psychological disturbance in children of primary age.
Explore the source record for details and available documents.
Child↗
Quantitative assessment of the mecholyl (Funkenstein) test.
Explore the source record for details and available documents.
Bipolar Disorder↗
Discovery and design of novel inhibitors of botulinus neurotoxin A: targeted 'hinge' peptide libraries.
Intoxication by the zinc protease botulinus neurotoxin A (BoNT-A) results from cleavage of a single Q-R bond in the neuronal protein SNAP-25, which disables the docking mechanism required for neurotransmitter release. In the present study, potential inhibitors of BoNT-A were assessed from their effects on the BoNT-A cleavage of a synthetic 17-mer peptide (SNAP-25, residues 187-203) spanning the Q-R cleavage site. Compounds that inhibited BoNT-A included thiols (zinc chelators) such as dithiothreitol, dimercaptopropanesulfonic acid, mercaptosuccinic acid and captopril. In addition, compounds containing multiple acidic functions, such as the SNARE motif V2 (ELDDRADALQ), the tripeptide Glu-Glu-Glu and the steroid glycoside glycyrrhizic acid, were effective inhibitors. 'Hinge' peptide mini-libraries (PMLs) having the structure acetyl-X(1)-X(2)-linker-X(3)-X(4)-NH(2) or X(1)-X(2)-linker-X(3), where X(1)-X(4) were mixtures of selected amino acids and the flexible linker was 4-aminobutyric acid, also provided effective inhibition. Targeted PMLs containing the acidic amino acids Asp and Glu, the scissile-bond amino acids Gln and Arg and the zinc chelators His and Cys produced pronounced inhibition of BoNT-A. Deconvolution of these libraries will provide novel ligands with improved inhibitory potency as leads in the design of peptide mimetics to treat BoNT poisoning.
Antitoxins↗
Preoperative identification of psychiatric illness in aesthetic facial surgery patients.
The purpose of this study was to evaluate the preoperative use of a two-part standardized assessment program (Prime-MD, Biometrics Research Department, New York State Psychiatric Institute) to objectively detect psychiatric disorders in facial plastic surgery patients, and to compare its use to findings identified by the facial plastic surgeon. Seventy-five new patients requesting aesthetic facial surgery at two academic centers and two private practice locations were evaluated.
Face↗
A new comparison group for research on child sexual abuse.
This paper discusses a new type of comparison group for research on adult survivors of child sexual abuse (CSA). A No Sexual Trauma Comparison Group excludes women who have experienced, during adulthood, a sexual trauma similar in impact to CSA. Using this type of comparison group increases sensitivity to (i.e., the likelihood of detecting) clinically relevant characteristics of CSA survivors.
Adolescent↗
Characteristics of autism as assessed by the Diagnostic Assessment for the Severely Handicapped-II (DASH-II).
The present study involved 1245 individuals with severe and profound mental retardation. Individuals with and without autistic features as assessed by the DASH-II were compared on demographic variables and symptomatology. The core and associated features of autism in severely and profoundly mentally retarded population were identified. Characteristics of persons with autistic disorders are reviewed, and the implications of the results are discussed.
Adult↗
Do anxiety disorders exist in persons with severe and profound mental retardation?
Sixty-nine individuals with severe and profound mental retardation were selected from 289 clients and studied for possible anxiety disorders. The validity of the DASH-II anxiety subscale was evaluated to determine its value in categorizing individuals with and without anxiety. Our findings were mixed. Only behavioral symptoms associated with anxiety could be reliably assessed in these individuals. Unfortunately; this ruled out many core symptoms of the disorder. Implications of the findings are discussed.
Anxiety Disorders↗
Characteristics of stereotypic movement disorder and self-injurious behavior assessed with the Diagnostic Assessment for the Severely Handicapped (DASH-II).
The first experiment involved 143 individuals with severe and profound mental retardation. Individuals with Stereotypic Movement Disorder, Self-Injurious Behavior (SIB), and Stereotypic movement disorder with self-injurious behavior as assessed by the Diagnostic Assessment for the Severely Handicapped-II DASH-II were validated against Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV; American Psychiatric Association, 1994) criteria. In a second study DASH-II scores for 1480 individuals with severe and profound mental retardation were compared on demographic variables, core and associated features of each disorder. Characteristics of persons in each group were reviewed. Persons with profound mental retardation were more likely to evince stereotypies or self-injury compared to their severely impaired counterparts. Also, those with stereotypies were more likely to present with Pervasive Developmental Disorder (PDD)/autism, organicity, and eating disorders, while persons with SIB were more likely to evince sleep, sexual, and eating disorders.
Adult↗
Characteristics of depression as assessed by the Diagnostic Assessment for the Severely Handicapped-II (DASH-II).
Fifty-seven individuals with severe and profound mental retardation (18 with a DSM-IV diagnosis of depression, 19 with a Diagnostic Statistical Manual, 4th edition diagnosis of autism, and 20 who meet no criteria for an emotional disorder) were studied. The validity of the Diagnostic Assessment for the Severely Handicapped II depression subscale was evaluated to determine its value in categorizing individuals in these two groups. Suggestions were made for diagnosing depression in persons with severe and profound mental retardation. In a second study the above individuals were compared on symptomology to assess comorbidity with related symptoms. These "core," peripheral, or associated features of depression were identified. Implications of the findings for describing and defining depression in these persons are discussed.
Adult↗
Combining utilization management and discharge planning.
Utilization management and discharge planning are two essential functions for all healthcare facilities. In many hospitals, these two jobs are performed by personnel from two separate departments. This article describes the methodology and benefits of a project that combined the functions of utilization management and discharge planning.
Education, Continuing↗
Regulatory decision strategy for entry of a novel biological therapeutic with a clinically unmonitorable toxicity into clinical trials: pre-IND meetings and a case example.
The following material was derived from a synthesis of case histories taken from investigational new drug (IND) applications and drug sponsors' experiences, utilizing fictionalized data to avoid any resemblance to any proprietary information; any such resemblance is accidental. These examples are used as an instructional scenario to illustrate appropriate handling of a difficult toxicology issue. In this scenario, a drug caused a toxicity in animals that was detected only by histopathologic analysis; if it were to develop in patients, no conventional clinical methods could be identified to monitor for it. It is not unusual for a firm to cancel clinical development plans for a lead drug candidate that causes such a toxicity, especially if such a drug is intended for use as a chronic therapeutic in a population of patients with a chronic disease. This case synthesis was inspired by a Food and Drug Administration (FDA) agreement to allow such a product to proceed into clinical trials after substantive pre-IND discussions and agreement on well-considered toxicology program designs. The scientists most closely involved in the strategy development included the sponsor's toxicologist, veterinary toxicologic pathologist, and pharmacokineticist, as well as the FDA's reviewing pharmacologist. The basis of this decision was thorough toxicity characterization (1-month studies in 2 species); correlating toxicities with a particular cumulative area under the curve (AUC) in both species; identification of the most sensitive species (the species that showed the lower AUC correlating with toxicity); allometric assessment of clearance of the drug in 3 nonhuman species; construction of a model of human kinetics (based on extrapolation from animal kinetics); and finally, estimation of clinical safety factors (ratios of the human estimated cumulative AUC at the proposed clinical doses, over the animal cumulative AUC that correlated with the no adverse effect levels). Industry and FDA scientists negotiated a joint assessment of risk and benefit in patients, resulting in the FDA permitting such a compound to enter into clinical trials for a serious autoimmune disease. Such constructive, early communication starts with the pre-IND meeting, and the conduct and planning for this meeting can be very important in establishing smooth scientific and regulatory groundwork for the future of a drug under IND investigation.
Animals↗
Cause and effects of renal failure.
Explore the source record for details and available documents.
Acute Kidney Injury↗
Metabolism and disposition of gemcitabine, and oncolytic deoxycytidine analog, in mice, rats, and dogs.
Gemcitabine, 2'-deoxy-2',2'-difluorocytidine, is a broad spectrum oncolytic compound with antitumor activity in solid tumor models. The pharmacokinetics, metabolism, and disposition of gemcitabine was examined in mice, rats, and dogs. All three species metabolize gemcitabine by deamination to the uracil metabolite. However, deamination in the mouse and dog was more extensive than in the rat. The mouse deaminated gemcitabine rapidly with the plasma concentration maximum of the uracil metabolite of gemcitabine being attained at 15 min postdosing compared with approximately 3 and 6 hr in the dog and rat, respectively. The rapid deamination in the mouse was also reflected in the plasma half-life of the parent compound. The mouse exhibited the shortest plasma half-life, approximately 0.28 hr, contrasted with 2.14 and 1.38 hr half-lives in rat and dog, respectively. Plasma AUC for the uracil metabolite of gemcitabine was 73%, 10.5%, and 315% of that for gemcitabine in the mouse, rat, and dog, respectively. Tissue concentrations of gemcitabine-derived radioactivity in the rat and mouse indicated that gemcitabine was rapidly distributed throughout the body. Half-lives of radioactivity in tissues of both the rat and mouse were relatively short, with the longest tissue half-lives of 5.7 and 3.0 hr, respectively. Plasma protein binding is negligible in all three species. The major route of elimination is via the urine in all three species with 76-86% of the dose excreted in the first 24 hr. The predominant radiolabeled component isolated from urine was gemcitabine in the rat and its uracil metabolite in the mouse and dog.
Animals↗
Nonoperative management of acute epidural hematoma diagnosed by CT: the neuroradiologist's role.
PURPOSE: To determine whether certain patients with epidural hematomas would benefit from conservative treatment and to assess the neuroradiologist's role in decision-making. METHODS: We reviewed the CT scan findings, clinical presentation and outcome of 48 consecutive patients with epidural hematoma managed at our institution within the past 5 years. In 18 patients, initial management was nonsurgical, and only one of these went on to require surgery due to clinical deterioration and evidence of enlargement of hematoma on CT. The remainder of these 18 did well without surgery. OBSERVATIONS AND CONCLUSIONS: Clinical indicators of neurologic dysfunction (decrease in Glasgow coma scale score, pupillary dilatation, and hemiparesis) in the presence of even small epidural hematomas usually dictates the need for surgical management. The role of the neuroradiologist is most important when the patient presents in a good clinical state, when identification of both favorable and unfavorable prognostic factors on Ct is essential. The initial diameter of nonsurgically managed epidural hematomas generally must be small (mean, 1.26 cm in our series, all under 1.5 cm), and midline shift should be minimal (mean, 1.8 mm in our series). The identification of lucent areas within the epidural hematoma (suggesting active bleeding), or CT evidence of uncal herniation, can be ominous and the neurosurgeon must be alerted to their presence. Even in the presence of a favorable clinical status, presence of a larger epidural hematoma with significant mass effect or central lucent areas should alert the neuroradiologist and neurosurgeon to the strong possibility of sudden neurologic deterioration, and indicate the probable need for surgical management.
Acute Disease↗
Region X: history of Branch 5, Oregon.
Explore the source record for details and available documents.
History, 20th Century↗
The metabolism of 2- and 3-hydroxyacetanilide. Determination of metabolic products by liquid chromatography/electrochemistry.
The metabolism of 2- and 3-hydroxyacetanilide was examined in incubations with mouse liver microsomes. Metabolic products were determined by a comparison of both chromatographic and electrochemical properties with that of reference materials. Using this technique, 3-hydroxyacetaminophen and 2-acetamidohydroquinone were positively identified as microsomal metabolites of 3-hydroxyacetanilide. Incubation of 2-hydroxyacetanilide with liver microsomes resulted in the formation of 2-acetamidohydroquinone. Deacetylation products, ortho- and meta-aminophenol were observed but were apparently formed through NADPH-independent processes. Tentative identifications were made for the formation of sulfhydryl adducts from 3-hydroxyacetanilide, 2-acetamidohydroquinone, and 2-hydroxyacetanilide but not from 3-hydroxyacetanilide. The microsomal metabolism was compared with in vivo metabolism through the analysis of urine from mice administered 200 mg/kg (ip) dosages of the hydroxyacetanilides. The parent compounds and their dihydroxylated metabolites were excreted primarily as sulfate and glucuronide conjugates. Conjugated o-aminophenol was detected in urine following 2-hydroxyacetanilide administration, but m-aminophenol was not observed in urine from mice receiving the meta isomer. Mercapturates of the above compounds were not detected in any of the urines.
Acetanilides↗