ABSTRACT
An increasing number of hazard assessment tools and approaches are being used in the marketplace as a means to differentiate products and ingredients with lower versus higher hazards or to certify what some call greener chemical ingredients in consumer products. Some leading retailers have established policies for product manufacturers and their suppliers to disclose chemical ingredients and their related hazard characteristics often specifying what tools to use. To date, no data exists that show a tool's reliability to provide consistent, credible screening-level hazard scores that can inform greener product selection. We conducted a small pilot study to understand and compare the hazard scoring of several hazard screening tools to determine if hazard and toxicity profiles for chemicals differ. Seven chemicals were selected that represent both natural and man-made chemistries as well as a range of toxicological activity. We conducted the assessments according to each tool provider's guidelines, which included factors such as endpoints, weighting preferences, sources of information, and treatment of data gaps. The results indicate the tools varied in the level of discrimination seen in the scores for these 7 chemicals and that tool classifications of the same chemical varied widely between the tools, ranging from little or no hazard or toxicity to very high hazard or toxicity. The results also highlight the need for transparency in describing the basis for the tool's hazard scores and suggest possible enhancements. Based on this pilot study, tools should not be generalized to fit all situations because their evaluations are context-specific. Before choosing a tool or approach, it is critical that the assessment rationale be clearly defined and matches the selected tool or approach. Integr Environ Assess Manag 2017;13:139-154. © 2016 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals, Inc. on behalf of SETAC.
Subject(s)
Hazardous Substances/toxicity , Toxicity Tests/methods , Hazardous Substances/standards , Risk Assessment/methods , Toxicity Tests/standardsABSTRACT
In trauma management, the importance of early and effective control of the airway is acknowledged universally. Attention to the airway is particularly vital when a casualty has sustained serious head or facial injuries. A cuffed tracheal tube has generally been regarded as the airway adjunct of choice in such cases. However, the attempted insertion of a tracheal tube under direct laryngoscopy is associated with a number of practical problems in pre-hospital trauma care. A case is described in which the intubating laryngeal mask airway (ILMA or LMA-Fastrach) was used successfully in the pre-hospital setting to secure the airway of a patient who had sustained serious head and facial injuries in a road traffic collision. The indications for the use of the ILMA in pre-hospital care are discussed.
Subject(s)
Laryngeal Masks , Craniocerebral Trauma/therapy , Emergency Medical Services , Facial Injuries/therapy , Humans , Intubation, Intratracheal , Male , Middle AgedABSTRACT
Mechanism-based inhibitors of human cytomegalovirus (HCMV) protease have been designed based on the pyrrolidine-5,5-trans-lactam ring system. New routes to the beta-methyl-, desmethyl-, and alpha-methyl-pyrrolidine-5,5-trans-lactam templates have been developed from 2,4-diaminobutyric acid. ESI/MS studies have shown that these inhibitors can bind covalently and reversibly to the viral enzyme in a time-dependent manner by a mechanism which is consistent with acylation of HCMV deltaAla protease at the active site nucleophile Ser 132. SAR in this series of pyrrolidine-5, 5-trans-lactams has defined the relative stereochemisty of the methyl substituent adjacent to the lactam carbonyl, the functionality on the lactam nitrogen, and the mechanism of action of this novel series of serine protease inhibitors against the HCMV deltaAla protease. Activity decreases on moving from the alpha-methyl to the desmethyl to the beta-methyl series. This selectivity is the opposite of that observed for these templates against the elastase and thrombin enzymes. The activity against HCMV deltaAla protease is the greatest with inhibitors based on the Cbz-protected alpha-methyl-5,5-trans-lactam template which have low micromolar activity against the viral enzyme.
Subject(s)
Cytomegalovirus/chemistry , Lactams/chemical synthesis , Pyrroles/chemical synthesis , Serine Endopeptidases/chemistry , Serine Proteinase Inhibitors/chemical synthesis , Drug Design , Humans , Lactams/chemistry , Pyrroles/chemistry , Serine Proteinase Inhibitors/chemistry , Stereoisomerism , Structure-Activity RelationshipABSTRACT
A novel fluoropyrazole ribonucleoside has been shown to have significant anti-influenza activity in vitro. The compound is compared and contrasted with the structurally-related compound ribavirin in attempts to identify factors having significant bearing on the mode of action of both compounds.
Subject(s)
Antiviral Agents/chemical synthesis , Nucleosides/chemical synthesis , Ribavirin/analogs & derivatives , Antiviral Agents/pharmacology , DNA-Directed RNA Polymerases/antagonists & inhibitors , Enzyme Inhibitors/chemical synthesis , Enzyme Inhibitors/pharmacology , Fluorine Compounds/chemical synthesis , IMP Dehydrogenase/antagonists & inhibitors , Influenza A virus/drug effects , Influenza B virus/drug effects , Intestinal Absorption , Molecular Structure , Pyrazoles/chemical synthesis , Ribavirin/chemical synthesis , Ribose/analogs & derivativesABSTRACT
PURPOSE: to learn about mobile mammography in the United States. MATERIALS AND METHODS: A survey of 82 questions was designed, pilot tested, and sent to mobile mammography facilities. The questions addressed many aspects of mobile programs, including administrative, financial, equipment, personnel, film processing, quality assurance, and communication of results. RESULTS: Of the 367 facilities that were mailed surveys, 159 facilities completed the survey, and 30 (19%) of those had discontinued their mobile programs. Seventy-six of 158 (48%) mobile facilities had performed mobile mammography for 1-5 years, and 69 of 158 (44%) had performed mobile mammography for more than 5 years. Seventy-two of 156 (46%) facilities were hospital-owned, and 25 of 156 (16%) were radiologist-owned. One hundred seven of 159 (67%) mobile facilities performed screening only. One hundred fourteen of 152 (75%) facilities charged +80.00 or less for screening. Mobile facilities averaged 20 examinations per day and served diverse populations. Sixty-seven of 159 (42%) facilities accepted self-referred women. Thirty-one percent of the facilities performed on-board processing. Only 71 of 149 (47%) facilities were financially profitable or breaking even, but 112 of 154 (73%) facilities would undertake a mobile project again. CONCLUSION: Mobile programs provide an opportunity to increase access to screening mammography, but they face many obstacles.
Subject(s)
Mammography/statistics & numerical data , Mobile Health Units/statistics & numerical data , Data Collection , Female , Humans , United StatesABSTRACT
Tobacco streak virus (TSV) RNA and alfalfa mosaic virus (AIMV) RNA will replicate only if a few copies of their coat proteins are bound to the RNA. To understand this phenomenon experiments were performed to find unique features of the TSV and AIMV subunits. Atomic absorption analysis showed that TSV and AIMV contained substantial quantities of zinc in native virions (approximately one zinc atom per four protein subunits in TSV and one zinc atom per two protein subunits in AIMV), while other plant viruses tested did not. Treatment of TSV with a zinc-extracting reagent resulted in partial degradation of all the TSV nucleoprotein components, although the top component was most effected. The sequence (Cys X2 Cys X10 Cys X2 His) was found between residues 28 and 45 in the TSV primary structure and it is similar to a sequence found in several nucleic acid-binding, gene-regulatory proteins, most notably transcription factor IIIA from Xenopus laevis. TSV subunits were found to be extensively crosslinked within the virions. TSV and AIMV contain sequences rich in basic residues in the amino-terminal portion of the subunit (residues 51 to 72 in TSV and 1 to 26 in AIMV) and helical predictions suggested modes of protein-nucleic acid interactions in these regions similar to those proposed for histones. Two potential sites for glycosylation were identified near the amino terminus of the TSV sequence. Controlled treatment of TSV with trypsin removed 87 residues from the amino terminus and produced a monomer of cleaved protein, as analysed by SDS-PAGE.(ABSTRACT TRUNCATED AT 250 WORDS)
Subject(s)
Capsid/metabolism , DNA-Binding Proteins/metabolism , Metalloproteins/metabolism , Plant Viruses/metabolism , Amino Acid Sequence , Electrophoresis, Polyacrylamide Gel , Medicago sativa , Molecular Sequence Data , Mosaic Viruses/metabolism , RNA, Viral/biosynthesis , Trypsin/metabolism , Zinc/analysisABSTRACT
Studies on 1,476 intravenous urographic examinations done in a 15-month period showed that the proportion of abnormal results varied widely-from 20% in patients with abdominal pain other than renal colic to 92% of those in prostatism. Patients with the strongest clinical evidence of haematuria were the most likely to have abnormal urograms, and to undergo cystoscopy with abnormal findings on this examination. All six patients with renal hypertension showed abnormalities other than on the urogram. Prior use of other tests may increase the effectiveness of urography.
Subject(s)
Urography , Abdomen, Acute/diagnostic imaging , Cystoscopy , Family Practice , Hematuria/diagnostic imaging , Hematuria/etiology , Hospitals , Humans , Hypertension, Renal/complications , Hypertension, Renal/diagnostic imaging , Kidney/abnormalities , Kidney Diseases/complications , Kidney Diseases/diagnostic imaging , Male , Outpatient Clinics, Hospital , Prostatic Diseases/complications , Prostatic Diseases/diagnostic imagingABSTRACT
A self-administered questionnaire designed for prerecording the routine clinical information required from outpatients has been found to be acceptable to them. Such a questionnaire should greatly ease the collection and recording of basic clinical information and offer the doctor more effective use of his time. With the questionnaire more information was recorded and therefore available in the case notes than at a conventional doctor-patient consultation. No administrative problems occurred in its distribution, use, and return.
Subject(s)
Medical History Taking , Outpatient Clinics, Hospital , Surveys and Questionnaires , Aged , Alcohol Drinking , Family Characteristics , Female , Humans , London , Male , Occupations , Physician-Patient Relations , Smoking , TravelSubject(s)
Munchausen Syndrome , Female , Hospitalization , Hospitals, General , Hospitals, Teaching , Humans , Medical Records , Middle AgedSubject(s)
Sjogren's Syndrome , Adult , Aged , Arthritis/complications , Arthritis, Rheumatoid/complications , Biopsy , Connective Tissue , Eye Manifestations , Female , Gingiva/pathology , Humans , Keratitis/pathology , Male , Middle Aged , Muscles/physiopathology , Neurologic Manifestations , Oral Manifestations , Parotid Gland/pathology , Sjogren's Syndrome/classification , Sjogren's Syndrome/epidemiology , Skin Manifestations , Staining and Labeling , Tongue/pathologySubject(s)
Adrenocorticotropic Hormone/metabolism , Carcinoma, Adenoid Cystic/metabolism , Hormones, Ectopic/metabolism , Lung Neoplasms/metabolism , Adrenocorticotropic Hormone/blood , Adult , Aged , Female , Humans , Hydrocortisone/blood , Hydrocortisone/urine , Male , Middle Aged , Paraneoplastic Endocrine Syndromes/diagnosisABSTRACT
The family of a woman with multiple autoimmune diseases has been investigated. Clinical evidence of an autoimmune disorder was detected in two relatives, and five others had serological and immunoglobulin abnormalities. It is suggested that there is an inherited predisposition to develop immunological abnormalities, and that a number of associated autoimmune diseases may develop in families in which this occurs.
Subject(s)
Autoimmune Diseases/genetics , Adult , Aged , Antibodies/analysis , Antibodies, Antinuclear/analysis , Complement Fixation Tests , Coombs Test , Female , Hemagglutination Tests , Humans , Immunoglobulin A/analysis , Immunoglobulin G/analysis , Immunoglobulin M/analysis , Male , Middle Aged , Mitochondria/immunology , Muscle, Smooth/immunology , Pedigree , Rheumatoid Factor/analysis , Syphilis Serodiagnosis , ThyroglobulinABSTRACT
The discovery of a case of renal tubular acidosis and fibrosing alveolitis led to the investigation of 19 further patients. Abnormal pulmonary function tests were found in a further four patients with overt renal tubular acidosis and in four out of eight patients with "incomplete" renal tubular acidosis. The response to an ammonium chloride test in seven patients with cryptogenic fibrosing alveolitis was normal. Those patients with a defect of both renal acidification and pulmonary gas transfer had concurrent autoimmune diseases such as Sjögren's syndrome and primary biliary cirrhosis. It is suggested that the renal and pulmonary abnormalities may be part of a systemic disorder capable of affecting many organs. Moreover, hyperglobulinaemia and autoantibodies in these patients further suggests that immunological mechanisms are concerned in the pathogenesis of these abnormalities.
Subject(s)
Acidosis, Renal Tubular/complications , Pulmonary Fibrosis/complications , Acidosis, Renal Tubular/etiology , Adult , Ammonium Chloride , Autoantibodies/analysis , Autoimmune Diseases/complications , Female , Humans , Hypergammaglobulinemia/complications , Immunoglobulins/analysis , Liver Cirrhosis, Biliary/complications , Pulmonary Fibrosis/etiology , Respiration , Sjogren's Syndrome/complications , SpirometrySubject(s)
Acidosis, Renal Tubular/immunology , Autoimmune Diseases , Thyroid Diseases/immunology , Acidosis, Renal Tubular/complications , Adult , Aged , Antibody Specificity , Antigen-Antibody Reactions , Autoantibodies/analysis , Chronic Disease , Female , Humans , Hyperthyroidism/immunology , Immunoglobulins/analysis , Kidney Function Tests , Lymphocyte Activation , Middle Aged , Myxedema/immunology , Neurologic Manifestations , Sjogren's Syndrome/immunology , Thyroid Function Tests , Thyroiditis, Autoimmune/immunologyABSTRACT
Sixty-three patients with liver disease were studied for the presence of the components of Sjögren's syndrome. The "sicca complex" (that is, patients without arthritis) was detected in 42% of patients with active chronic hepatitis, 72% with primary biliary cirrhosis, and 38% with cryptogenic cirrhosis. One patient with active chronic hepatitis and one with primary biliary cirrhosis had rheumatoid arthritis. No evidence of Sjögren's syndrome was detected in seven patients with alcoholic cirrhosis. It is suggested that the sicca complex and autoimmune liver disease may be part of a systemic disorder in which immunological mechanisms are concerned in the pathogenesis.
Subject(s)
Liver Diseases/complications , Sjogren's Syndrome/complications , Adult , Aged , Arthritis, Rheumatoid/complications , Autoantibodies/analysis , Autoimmune Diseases/complications , Biliary Tract Diseases/complications , Chronic Disease , Female , Hepatitis/complications , Humans , Immunoglobulins/analysis , Liver Cirrhosis/complications , Liver Function Tests , Male , Middle AgedABSTRACT
Of nine women with hyperglobulinaemic renal tubular acidosis four presented with acidosis and five had the "incomplete" form of the disorder. Seven patients had nephrogenic diabetes insipidus, but none had the Fanconi syndrome. Investigation showed abnormal immunoglobulins and autoantibodies in all nine patients. Diseases coexisting with renal tubular acidosis were Sjögren's syndrome, hyperglobulinaemic purpura, autoimmune liver and thyroid disease, diffuse pulmonary fibrosis, and a peripheral neuropathy. It is suggested that this type of renal tubular acidosis might be due to an autoimmune process.