Job exposure matrices for occupational respiratory disease: a narrative review.

BACKGROUND: Job exposure matrices (JEMs) are epidemiological tools used to provide estimations of occupational exposures when it is not feasible to complete detailed individual occupational histories. AIMS: To identify and summarize the characteristics of published general population JEMs (GPJEM) of inhalable occupational exposures applied in studies of respiratory disease. METHODS: MEDLINE and EMBASE databases were searched using pre-defined search terms, with screening performed by two independent reviewers to identify studies reporting the use of a GPJEM. JEM creation papers were subsequently identified and reviewed for each individual GPJEM, noting its characteristics in terms of occupational classification system and exposure estimates. RESULTS: From 728 studies identified in initial searches, 33 GPJEMs of inhalable occupational exposures were identified. Versions of the International Standards Classification of Occupations were the most used occupational classification system. Binary, probability and intensity-based exposure estimates were most frequently reported in GPJEMs. CONCLUSIONS: Selection of a GPJEM to apply in epidemiological research should be based on the exposure(s) of interest, time period of occupations under review, geographical region for intended use, occupation classification system used and the exposure estimate outcome.

Occupational asthma in teachers.

BACKGROUND: Work-related asthma symptoms are common in teachers and teaching assistants, there are few studies evaluating their causes. AIMS: To identify causes of occupational asthma in teachers and teaching assistants referred to the Birmingham Occupational Lung Disease clinic 2000-20 using evaluation of serial Peak Expiratory Flow (PEF) records. METHODS: Teachers and teaching assistants with possible occupational asthma were asked to record PEF 2-hourly at home and work for 4 weeks. Their records were evaluated with the Oasys programme. Those with a positive score for any of the three scores (area between curves (ABC), timepoint and Oasys score from discriminant analysis) were included. Repeat records were made as indicated to help identify the cause and the effects of remedial actions. RESULTS: Thirty-eight teachers or teaching assistants met the inclusion criteria with all three Oasys scores positive in 24, 2/3 scores in nine and 1/3 in five. The building was the likely cause in 17 (in new builds particularly acrylates from carpet adhesives and in old buildings mould and construction dust), bystander exposure to agents in the schools in 12 (cleaning agents, acrylates from photocopiers and chloramines from indoor pools) and materials used in the classroom in 9 (most commonly MDF in design and technology classes). We illustrate how the PEF records helped identify the cause. CONCLUSIONS: Oasys analysis of PEF records is a useful method of evaluating occupational asthma in teachers and identified difficult to confirm causes where successful remediation or redeployment was achieved.

Occupational asthma in office workers.

BACKGROUND: Office work has a relative perception of safety for the worker. Data from surveillance schemes and population-based epidemiological studies suggest that office work carries a low risk of occupational asthma (OA). Office workers are frequently used as comparators in studies of occupational exposure and respiratory disease. AIMS: We aimed to describe and illustrate our tertiary clinical experience of diagnosing OA in office workers. METHODS: We searched the Birmingham NHS Occupational Lung Disease Service clinical database for cases of occupational respiratory disease diagnosed between 2002 and 2020, caused by office work or in office workers. For patients with OA, we gathered existing data on demographics, diagnostic tests including Occupational Asthma SYStem (OASYS) analysis of serial peak expiratory flow and specific inhalational challenge, and employment outcome. We summarised data and displayed them alongside illustrative cases. RESULTS: There were 47 cases of OA (5% of all asthma) confirmed using OASYS analysis of PEFs in the majority. Sixty percent of cases occurred in healthcare, education and government sectors. The most frequently implicated causative exposures or agents were: indoor air (9), printing, copying and laminating (7), cleaning chemicals (4), mould and damp (4), and acrylic flooring and adhesives (4). Exposures were grouped into internal office environment, office ventilation-related and adjacent environment. CONCLUSIONS: Clinicians should be vigilant for exposures associated with OA in office workers who present with work-related symptoms, where respiratory sensitizing agents may be present. A structured approach to assessment of the workplace is recommended.

Updated review of reported cases of reactive airways dysfunction syndrome.

BACKGROUND: A previous systematic review of the diagnosis of reactive airways dysfunction syndrome (RADS), undertaken from 1985 to 2004, found a lack of standardization of case reporting, thus misattribution of symptoms can occur. AIMS: We aimed to update the systematic review, update the list of reported causes and see whether a more structured approach to reporting has been adopted. METHODS: We undertook a systematic literature review, using the databases EMBASE and Ovid MEDLINE, with search terms 'reactive airways dysfunction syndrome' or 'asthma AND acute irritant', and reported according to PRISMA guidelines. We included papers and abstracts published from January 2005 to September 2019, and articles were grouped by the presence or absence of diagnostic features: 'definite' RADS (met Brooks' criteria) or 'possible' RADS (Brooks' criteria not met or insufficient data). We collected demographic and diagnostic data for cases, where given. RESULTS: Eleven papers and six conference abstracts met the inclusion criteria, 13 of which were case series or reports, and comprised 752 cases in total; seven articles met Brooks' criteria for RADS diagnosis. A variety of agents were implicated, with chlorine or chlorine-releasing molecules most frequently reported. CONCLUSIONS: A lack of standardized reporting of RADS remains. The majority of published articles and conference abstracts either do not meet, or contain insufficient data to judge against, Brooks' criteria, particularly in relation to onset of symptoms and bronchial hyper-reactivity or variability of airflow obstruction. Some novel agents are described, in keeping with recognized structural taxonomies.

Cardiac SABR: Image matching techniques for accurate treatment delivery.

BACKGROUND: Ventricular tachycardia is an irregular heartbeat conventionally treated using invasive cardiac catheter ablation and medication. However, when standard treatments have been exhausted, cardiac SABR provides a final treatment option to this high-mortality condition. Complex diagnostic mapping and planning scans enable multi-disciplinary target delineation for a 25Gy single fraction. However, organs at risk (OAR) near the target make this treatment challenging to plan and deliver. Publications from cardiologists report the efficacy of cardiac SABR, however there is limited data on the treatment delivery and image matching of this complex procedure. METHODS: Four specialist therapeutic radiographers experienced in cardiac SABR reviewed 40 CBCTs from 10 patients treated in the UK. Each therapeutic radiographer conducted five image matches: a manual match (manual), an automatic match to the heart structure (auto) and the auto match followed by manual adjustment to the PTV (PTV), all using three degrees of freedom (DoF) only. The auto and PTV matches were also repeated using 6DoF. Inter-observer variability was quantified using 95% limits of agreement from a modified Bland-Altman analysis. RESULTS: The limits of agreement were smallest in the automatic matches suggesting the algorithm is reliable. A manual adjustment from the auto match to the PTV is clinically appropriate to optimise target coverage. The limits of agreement were smaller in the 6DoF PTV match 1.06 mm, 1.24 mm, 1.68 mm than the 3DoF PTV match 1.57 mm, 2.06 mm, 2.11 mm (lateral, vertical, longitudinal). CONCLUSION: The 6DoF CBCT image match has less variability and therefore suggest using a 6DoF couch for treatment delivery. IMPLICATIONS FOR PRACTICE: Cardiac SABR CBCT image matching at treatment delivery is complex, optimisation of CBCT acquisition parameters and therapeutic radiographer training is essential prior to implementation.

Long-term Overall Survival Outcomes in Patients with Early Stage, Peripherally Located, Non-small Cell Lung Cancer Treated with Stereotactic Ablative Radiotherapy in a Non-academic Cancer Centre.

AIMS: To report long-term outcomes of patients treated with stereotactic ablative radiotherapy (SABR) for early stage, peripherally located non-small cell lung cancer. MATERIALS AND METHODS: Data were collected retrospectively between September 2009 and May 2019. Electronic medical records were reviewed for baseline characteristics, treatment details and outcomes. All patients were treated according to local protocol based on the national UK SABR Consortium guidelines. Risk-adapted treatment schedules were used depending on the size and the location of the tumour (54 Gy in three fractions, 55 Gy in five fractions, 60 Gy in eight fractions or 50 Gy in 10 fractions). Overall survival outcomes were evaluated using the Kaplan-Meier method. RESULTS: In total, 412 patients were included in the analysis. The median age was 76 years (range 48-93 years). Histological confirmation was obtained in 233 cases (56.6%). The median overall survival for all patients was 42.3 months (95% confidence interval 37.3-47.3 months), with 3- and 5-year overall survival of 52.8% and 37.3%, respectively. For biopsy-proven patients (56.6%), 3- and 5-year overall survival was 57.3% and 40.1%, respectively. With respect to overall survival, univariate and multivariate analysis revealed no significant difference in survival by technique (volume-modulated arc therapy versus conformal; three-dimensional computed tomography versus four-dimensional computed tomography), tumour location, smoking status at first contact, pre-treatment tumour stage or pre-treatment standardised uptake value. Survival was poorer for patients who received the 50 Gy in 10 fractions schedule. Treatment was very well tolerated with very low rates of grade 3-4 toxicity (1%). CONCLUSIONS: SABR for peripherally located, medically inoperable non-small cell lung cancer can be safely and effectively implemented in a non-academic institution with appropriate equipment and training. Overall survival outcomes and toxicity rates are comparable with internationally published studies. Patients treated with 50 Gy in 10 fractions had a poorer survival outcome.

Evaluation of visceral larva migrans by radioimmunoassay systems.

A 9-year-old child with miliary pulmonary infiltrates, eosinophilia, and hyperimmunoglobulinemia E recovered rapidly cover a four-week period. Subsequent analysis of serum samples by a solid phase radioimmunoassay technique demonstrated IgM, IgE, and IgG antibodies to Ascaris suum antigen which declined following the acute phase of the illness in parallel with a decline in serum IgM, IgE, and IgG concentrations. Precipitating antibodies in serum against Ascaris antigen were demonstrated. The diagnosis is considered to be toxocariasis or ascariasis. The application of sensitive radioimmunoassay techniques of this type should provide a method of earlier diagnosis and the demonstration of rapidly changing antibody levels a method of confirming the diagnosis in parasitic diseases.

Histochemical diagnosis of Hirschsprung disease.

A histochemical staining technique for detection of acetylcholinesterase (AChE) in rectal suction biopsies was compared with the presence or absence of ganglion cells in full-thickness or suction biopsies for the diagnosis of Hirschsprung disease (HD) in infants and children. Biopsies from 55 of 58 children were adequate for both the AChE assay and routine pathologic examination for ganglion cells. Two patterns of AChE staining were noted. With pattern A, prominent nerve fibers staining for AChE were seen throughout the muscularis mucosa and the lamina propria. With pattern B, similar fibers were seen only in the muscularis mucosa and the areas of lamina propria that were immediately adjacent. No "false-negative" AChE staining reactions were found in patients with HD. No "false-positive" reactions showing pattern A were found. This pattern was diagnostic for HD. Three false-positive reactions were found showing pattern B in patients with conditions other than HD. Among 22 patients with HD, 19 were males and three were females. Pattern A occurred in all age groups and in both sexes. Pattern B in patients with HD was seen exclusively in male infants 1 month of age or less. Experience suggests that the AChE staining of rectal suction biopsies is an excellent screening test for HD in infants and children. If pattern B is encountered, however, the specimen should be examined by routine pathologic techniques for the presence of submucosal ganglion cells.

ABO hemolytic disease in Puerto Rico and North Carolina.

A prospective study was carried out at the University of Puerto Rico Hospital (UPRH) and at the North Carolina Baptist Hospital (NCBH) in order to establish the incidence of ABO hemolytic disease (ABO HD) in the two populations and to determine the relationship of intestinal parasitic infection of the mother to ABO HD in the infant. The incidence of ABO HD among UPRH at risk pregnancies (type O mother with type A or B infant) was 28.3% or 1 in 3.5 as compared with 18.4% or 1 in 5.4 of NCBH at risk pregnancies (P less than .05). Indirect Coombs' tests in cord sera, representing the passive transfer from mother to fetus of antibodies directed toward antigens on the infants' erythrocytes, were positive in 58.8% of UPRH at risk infants as opposed to 40.4% of NCBH at risk infants (P less than .001). Maternal isohemagglutinin titers at term were higher in type O UPRH mothers than in type O NCBH mothers (P less than .01). A relationship between helminth parasitic infection of the mother and ABO HD in the infant was suspected but not proved.

Reaction of COTC with glutathione: structure of the putative glyoxalase I inhibitor.

The structure of the active glyoxalase I inhibitor derived from the Streptomyces griseosporeus metabolite COTC 1 has been conclusively identified by means of total synthesis as 2c. Human glyoxalase I is competitively inhibited by 2c (K(i)() = 183 +/- 6 microM) but is not inhibited by 1 itself.

Common replication strategies emerging from the study of diverse groups of positive-strand RNA viruses.

Studies using brome mosaic virus (BMV), Sindbis virus and poliovirus have provided evidence that disparate groups of plant and animal positive strand RNA viruses have remarkably similar replication strategies. The conservation of several functional domains within virus-encoded nonstructural proteins implies that, although the precise character of these and interacting host components varies for each virus, they employ similar mechanisms for RNA replication. For (+) strand replication, similarities in cis-acting sequence motifs and RNA secondary structures within 5' termini of genomic (+) strands have been identified and have been shown to participate in binding of host factors. The model presented for replication of BMV RNA suggests that binding of these factors to internal control region (ICR) sequence motifs in the double-stranded replication intermediate releases a single-stranded 3' terminus on the (-) strand that may be essential for initiation of genomic (+) strand synthesis. ICR sequences internal to the BMV genome were also found to be required for efficient replication. Asymmetric production of excess genomic (+) over (-) strand RNA, characteristic of all (+) strand viruses, may be accomplished through transition of the replicase from competence for (-) to (+) strand synthesis by the recruitment of additional host factors.

Visceral larva migrans: Immunoglobulins, precipitating antibodies and detection of IgG and IgM antibodies against Ascaris antigen.

Serum samples from ten children with visceral larva migrans were evaluated by analysis of: immunoglobulin concentrations, precipitin reactions against Toxocara and Ascaris antigens and blood group substances, and IgM and IgG activity against Ascaris antigen by radioimmunoassay (RIA). The elevated concentrations of serum IgE and IgG and the positive precipitin reactions which occurred in some cases are an aid in diagnosis but were not consistently present. Serum IgM concentrations were elevated in all cases. IgM or IgG antibodies against Ascaris suum antigen were detected in all cases by a solid phase RIA technique. Radioimmunoassay techniques of this type may provide a superior method of diagnosis, particularly if used with serial serum samples which demonstrate changing levels of antibodies.

Analysis of RNA stability and (-) strand content in viral infections using biotinylated RNA probes.

Non-radioactive biotinylated RNA probes specific for plus (+) and minus (-) sense RNAs of brome mosaic virus (BMV) were synthesized in vitro from a plasmid bearing a 200 base pair fragment complementary to the 3' terminus of each of the three genomic RNAs of the virus. Using virion RNAs isolated from BMV infected barley plants, the sensitivity of biotinylated RNAs as hybridization probes was compared with that of 32P-labeled probes in Northern hybridization assays. Although the sensitivity of biotinylated and 32P-labeled probes is similar (approximately 5 pg), the time required to detect the RNA bands was much less than for autoradiography; (-) sense RNAs could be detected in 30 min whereas 48 h or more were required by autoradiography. The value of biotinylated probes for following RNA stability was exemplified by the detection of supplied inocula in protoplasts 24 h post-inoculation. Quantitation of relative accumulation of progeny (+) and (-) sense RNAs by densitometry of the Northern blots probed with biotinylated RNAs paralleled that of radiolabeled probes. The application of these probes was extended to the detection of RNAs in barley protoplasts and BMV infected plant sap by dot hybridization. In these tests, viral RNAs were detected in as few as 250 protoplasts and sap dilutions up to 1:2000. The merits of these non-radioactive probes in monitoring the replication events by the detection and quantitation of mutant progeny RNAs of BMV are discussed.

Cell-mediated hypersensitivity to mite antigens in atopic dermatitis.

Cell-mediated hypersensitivity (CMH) to house dust mite antigens, as determined by increased DNA synthesis after coculture of mononuclear cells with Dermatophagoides farinae extract, was demonstrated in 11 of 16 children with atopic dermatitis (AD) as compared with two of 14 control subjects. Patient and control responses peaked at the same antigen dose (12.4 micrograms of mite protein per 10(5) cells). Patient responses were significantly greater at all mite protein concentrations. The increased DNA synthesis of stimulated cells was demonstrated to be a T-cell response in the one patient in whom T-cell-enriched cultures were studied. There was no relationship between CMH and lgE-mediated hypersensitivity to D farinae in the patient group. It is suggested that AD is associated with CMH reactions to allergens and that antigen competition may be involved in the reduced CMH responses to mitogens and antigens noted by other investigators.

Standardizing the expression and nomenclature of cancer treatment regimens. American Society of Health-System Pharmacist (ASHP), American Medical Association (AMA), American Nurses Association (ANA).

Guidelines for describing cancer chemotherapy regimens in all aspects of drug development, including treatment protocols, order forms, and product labels, are proposed. To complement the approaches to reducing medication errors that have been recommended by ASHP and others, pharmacists at the National Institutes of Health and the National Cancer Institute, with the input of oncology pharmacists from diverse areas of practice, developed guidelines for expressing chemotherapy dosage schedules and treatment regimens. The guidelines present standards that are broadly applicable and can be adopted by other institutions. Clear and unambiguous expression of all medication orders and consistency of treatment descriptions are suggested. Written treatment plans and orders should contain enough information to allow health care providers from diverse disciplines to compare them with published treatment descriptions and investigational protocols and must therefore include planned dosages and schedules expressed in patient-specific units. In general, drug dosages should be expressed as the amount of drug administered from a single container. When ordering drugs that are part of complex or combination-drug regimens, prescribers should write as many of the orders at one time as is possible, so that continuity might be preserved. Standard rules are proposed for describing chemotherapy regimens.

Anhidrotic ectodermal dysplasia with transient hypogammaglobulinemia.

An 8-month-old white boy with anhidrotic ectodermal dysplasia (AED) who was referred to the North Carolina Baptist Hospital because of recurrent respiratory infections and hypogammaglobulinemia is presented. His mother had partial expression of AED suggesting x-linked recessive inheritance in this family. She was incidentally given oral glucocorticoids during pregnancy for the treatment of chronic urticaria. The patient's serum immunoglobulins G, A and M were low at 8 months but normal by 15 months of age, and immunologic evaluation failed to show a defect in antibody production or cell-mediated immunity. Although rare, the diagnosis of AED must be considered in infant boys with recurrent fever and respiratory infections. The diagnostic features of the disease may be subtle in young child prior to the eruption of the characteristic peg-shaped teeth.

Synthesis and biological evaluation of pyridin-2-one nucleosides.

The synthesis of 1-(beta-D-ribofuranosyl)pyridin-2-one-3-carboxylic acid and the 3-carboxamide as well as a short series of 3N-carboxamides, prepared by TPTU/HOBt coupling of primary amines with 1-(beta-D-ribofuranosyl)pyridin-2-one-3-carboxylic acid, and their evaluation as anti-infective agents is described.