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At least 379 records · Page 21Linked to original sources

Epidemic decompression sickness: case report, literature review, and clinical commentary.

BACKGROUND: Decompression sickness (DCS) is a syndrome of symptoms caused by bubbles of inert gas. These bubbles are produced by a significant ambient pressure drop. Although cases are usually solitary there have been several episodes of DCS clusters. This paper reports an episode of epidemic decompression sickness and reviews the literature. METHODS: The case reported describes six aircrewmen with DCS following an unpressurized AC-130 flight (maximum altitude 17,000 ft). Two obvious concerns-the low altitude at which DCS was encountered and the potential for epidemic hysteria-are discussed and discounted. In addition, factors contributing to this case are recounted in depth. Moreover, the literature was examined for similar cases of epidemic decompression sickness. Four other instances were discovered. Detailed qualitative analysis of these five reports was performed. RESULTS: With this information epidemic decompression sickness is defined and classified. Two types are described-individual-based (Epi-I) and population-based (Epi-P). Epi-I is a cluster of DCS following a solitary exposure; whereas, Epi-P is a cluster of DCS following multiple exposures over time. Investigation of Epi-P follows the classical rules of outbreak investigation (time, place, person, and environment); whereas, Epi-I does not. In fact, the focus in Epi-I is almost entirely the environment. Following this outline should produce an etiology that control measures can be directed against. However, it is prudent to look beyond the etiology. Enter the Haddon Matrix, a classic public health tool that considers counter-measures before, during, and after the event. CONCLUSION: These many concepts are illustrated with the presented case. Following this template, both the expert and the novice flight surgeon have a systematic and reproducible approach to these difficult puzzles.

Adult↗

Effects of fine and ultrafine sulfuric acid aerosols in guinea pigs: alterations in alveolar macrophage function and intracellular pH.

Acidic sulfate is the most toxicologically important sulfur oxide which exists in the ambient air. To determine if particle size influences toxic effects of sulfuric acid, we investigated the effects of sulfuric acid aerosols of two different sizes on biochemical and cellular parameters of bronchoalveolar lavage fluid from exposed guinea pigs. Guinea pigs were exposed to fine (mass median diameter, 0.3 micron), and ultrafine (mass median diameter, 0.04 micron) sulfuric acid aerosols at 300 micrograms/m3 for 3 hr/day. The animals were euthanized immediately and 24 hr after 1 and 4 days of exposure and lungs were lavaged. Elevated beta-glucuronidase, lactate dehydrogenase activities, and total protein concentration as well as decreased cell viability were observed in the lavage after a single exposure to sulfuric acid aerosols of both sizes. These alterations were small, though statistically significant, and transient. No alteration in these parameters was observed after 4 days of exposure to acid aerosols. In contrast, sulfuric acid-induced alterations in alveolar macrophage function were more pronounced and longer lasting. Immediately after a single exposure to fine acid, there was a 2.7-fold increase in the spontaneous tumor necrosis factor (TNF) release over that in the control group while endotoxin-stimulated TNF release was increased by 2.2-fold. In addition, acid aerosols of both sizes increased the TNF release from macrophages after 4 days of exposure, although there was no clear temporal pattern of induction or recovery. Furthermore, immediately after 4 days of exposure to either fine or ultrafine acid, the amount of H2O2 that could be induced from baseline production by alveolar macrophages was 2.2-fold higher than that of the controls. The phagocytic function of macrophages was also altered by exposure to sulfuric acid aerosols. Twenty-four hours after single or multiple exposure, fine acid enhanced (as high as 78% above control) the in vitro phagocytic activity of alveolar macrophages while ultrafine acid depressed the phagocytic capacity (as much as 50% below that in the control). In addition to these biochemical parameters and cellular functions, we also measured the intracellular pH (pHi) of macrophages harvested after exposures to these acid aerosols using a pH-sensitive fluorescent dye. The resting pHi was depressed after a single exposure to both acid aerosols. The depression in pHi persisted 24 hr after ultrafine acid exposure.(ABSTRACT TRUNCATED AT 400 WORDS)

Aerosols↗

GyrA sequence analysis of Staphylococcus aureus and methicillin-resistant S. aureus strains selected, in vitro, for high-level ciprofloxacin resistance.

Four methicillin-susceptible Staphylococcus aureus and eight methicillin-resistant S. aureus (MRSA) isolates, all of which were ciprofloxacin susceptible (MIC < 2.0 micrograms/ml) were manipulated, in vitro, to achieve high-level ciprofloxacin resistance by means of up to 14 passages onto media containing increasing concentrations of ciprofloxacin. Resistance to ciprofloxacin at a concentration of at least 512 micrograms/ml was achieved in all 12 isolates tested. This resistance was continually detected during weekly passage on antibiotic-free media for 12 weeks. The parent and daughter cells from four strains had their gyrA sequenced from amino acid (aa) codons 70-100, the region of previous mutations in high level quinolone-resistant S. aureus. Mutations at aa codon 84 were seen in three of four strains, but appeared at varying levels of ciprofloxacin resistance. High-level resistance of S. aureus and MRSA to ciprofloxacin can be developed in vitro using multiple exposures to incremental concentrations of the drug. It is apparently due to multiple mechanisms and, once established, remains stable over time.

Ciprofloxacin↗

Using molecular epidemiology in assessing exposure for risk assessment.

Quantitative estimation of health risks depends on exposure characterization, the nature of the dose response relationships, and the toxicity of the agents involved. The greatest uncertainties in risk assessment almost always arise from sparse or inadequate exposure data, inadequate understanding of exposure mechanisms, and insufficient understanding of the exposure-dose-response pathway. Additional sources of uncertainty arise when mixed or multiple exposures are implicated in the disease pathway, and as a result of variability in both exposures and responses within and between individuals. Here we consider the role of exposure assessment in the risk assessment process, the use of biological markers or molecular epidemiology to contribute to improvements in exposure assessment for risk assessment, and uncertainties associated with the use of biological markers.

Biomarkers↗

Principles for characterizing the potential human health effects from exposure to nanomaterials: elements of a screening strategy.

The rapid proliferation of many different engineered nanomaterials (defined as materials designed and produced to have structural features with at least one dimension of 100 nanometers or less) presents a dilemma to regulators regarding hazard identification. The International Life Sciences Institute Research Foundation/Risk Science Institute convened an expert working group to develop a screening strategy for the hazard identification of engineered nanomaterials. The working group report presents the elements of a screening strategy rather than a detailed testing protocol. Based on an evaluation of the limited data currently available, the report presents a broad data gathering strategy applicable to this early stage in the development of a risk assessment process for nanomaterials. Oral, dermal, inhalation, and injection routes of exposure are included recognizing that, depending on use patterns, exposure to nanomaterials may occur by any of these routes. The three key elements of the toxicity screening strategy are: Physicochemical Characteristics, In Vitro Assays (cellular and non-cellular), and In Vivo Assays. There is a strong likelihood that biological activity of nanoparticles will depend on physicochemical parameters not routinely considered in toxicity screening studies. Physicochemical properties that may be important in understanding the toxic effects of test materials include particle size and size distribution, agglomeration state, shape, crystal structure, chemical composition, surface area, surface chemistry, surface charge, and porosity. In vitro techniques allow specific biological and mechanistic pathways to be isolated and tested under controlled conditions, in ways that are not feasible in in vivo tests. Tests are suggested for portal-of-entry toxicity for lungs, skin, and the mucosal membranes, and target organ toxicity for endothelium, blood, spleen, liver, nervous system, heart, and kidney. Non-cellular assessment of nanoparticle durability, protein interactions, complement activation, and pro-oxidant activity is also considered. Tier 1 in vivo assays are proposed for pulmonary, oral, skin and injection exposures, and Tier 2 evaluations for pulmonary exposures are also proposed. Tier 1 evaluations include markers of inflammation, oxidant stress, and cell proliferation in portal-of-entry and selected remote organs and tissues. Tier 2 evaluations for pulmonary exposures could include deposition, translocation, and toxicokinetics and biopersistence studies; effects of multiple exposures; potential effects on the reproductive system, placenta, and fetus; alternative animal models; and mechanistic studies.

Journal Article↗

Meclofenomate inhibition of UV-induced erythema--a randomized, placebo-controlled, double-blind study.

Systemic intradermal and topical inhibitors of eicosanoid synthesis have been shown to decrease the intensity delay the onset of erythema produced with a single exposure to ultraviolet (UV) light. We studied the effect of single and multiple doses of meclofenomate on erythema induced by single and multiple doses of UV light. Thirty Caucasian subjects took either meclofenomate 100 mg t.i.d. or matching placebo for 5 days, crossing over to the alternative for 5 more days after a 2-day washout period. A statistical analysis was made of erythema response immediately prior to the study and then on 8 successive days during the study. Analysis of single and multiple exposure data revealed a statistically significant inhibition of erythema from meclofenomate therapy as compared with placebo.

Adult↗

Airway hyperresponsiveness, prevalence of chronic respiratory symptoms, and lung function in workers exposed to irritants.

The association between occupational exposure to airway irritants and the prevalence of chronic respiratory symptoms and level of lung function, and whether these associations were modified by airway hyperresponsiveness, smoking, and a history of allergy were studied in 668 workers from synthetic fibre plants. Respiratory symptoms were recorded with a self administered Dutch version of the British Medical Research Council questionnaire, with additional questions on allergy. Airway responsiveness was measured by a 30 second tidal breathing histamine challenge test. On the basis of job titles and working department, the current state of exposure of all workers was characterised as (1) no exposure, reference group; (2) white collar workers; (3) SO2 HCl, SO4(2); (4) polyester vapour; (5) oil mist and vapour; (6) polyamide and polyester vapour; (7) multiple exposure. Workers exposed to airway irritants were not simultaneously exposed to airborne dust. Airway hyperresponsiveness (AHR), defined as a 20% fall in forced expiratory volume in one second (FEV1) at < or = 32 mg/ml histamine, was present in 23% of the subjects. The association between exposure groups and prevalence of symptoms was estimated by means of multiple logistic regression; the association with level of lung function (forced vital capacity (FVC), FEV1, maximum mid-expiratory flow rate (MMEF)) was estimated by means of multiple linear regression. Both methods allow simultaneous adjustment for potential confounding factors. The exposure groups were associated with a higher prevalence of chronic respiratory symptoms. Lower prevalence of symptoms was found for workers exposed to SO2, HCl, and SO4(2-), most likely due to pre-employment selection procedures. Current smoking, AHR, and a history of allergy were significantly associated with a higher prevalence of chronic respiratory symptoms, independent of each other, and independent of irritant exposure. The association between exposure and prevalence of symptoms was greater in smokers than in ex-smokers and non-smokers. This difference was most clearly seen in the polyester vapour and polyamide and polyester vapour group. No modification of the association between exposure groups and prevalence of symptoms by airway hyperresponsiveness could be shown. The exposure groups were not significantly associated with a lower level of lung function. Adjustment for chronic respiratory symptoms did not change the results. There were no indications of a possible interaction between exposure and AHR, current smoking, or a history of allergy on lung function. Workers of the polyester vapour and the oil mist and vapour group with >10 years of exposure had a lower FEV1 (beta = -295 and -358 ml) and significantly lower MMEF (beta = -1080 and -1247 ml/s; p < 0.05) than the reference group. The number of workers of both group were, however, small (n = 10 and n = 13 respectively). More investigations between low level exposure to irritant and respiratory health.

Adult↗

Recurrent hepatitis following halothane exposures.

The existence of hepatotoxicity due to halothane remains subject to debate. Three cases are presented in which multiple exposures to halothane were followed in several instances by evidence of postoperative fever and/or hepatitis. In one case, hepatitis with bridging necrosis developed; the patient responded to long-term steroid therapy. In another, fulminant hepatic necrosis proved fatal. A brief review of halothane hepatitis is given. Otherwise unexplained fever and hepatitis following the use of halothane, especially if recurrent or accompanied by evidence of hypersensitivity, should contraindicate subsequent use of that drug.

Biopsy↗

Cancer prevention in the workplace and natural environment. A review of etiology, research design, and methods of risk reduction.

Guidelines for developing programs in cancer prevention and reduction of risk related to occupational and environmental carcinogens are provided in this review, which includes a summary of experimental and epidemiologic research designs for assessing potential etiologic agents, an overview of known occupational and environmental carcinogens, and a summary of general approaches to risk reduction. This review includes human cancer risks in the workplace and in the natural environment, which encompasses air pollution, water pollution, and hazardous waste disposal. Fourteen tables present the following: (1) established and probable carcinogens that may be encountered in the workplace, as contaminants of air or water, or as hazardous waste; (2) regulated carcinogens; (3) primary sources of exposure; (4) research designs; and (5) risk reduction methods. The interactive effects of multiple exposures are discussed as they relate to etiology and prevention. The importance of federal regulation is emphasized, as well as the need to understand the potential for cancer prevention in the context of broader economic, political and social issues.

Air Pollution↗

Cytotoxic effect of vanadium and oil-fired fly ash on hamster tracheal epithelium.

Hamster tracheal organ cultures were used to study the in vitro effects of vanadium and oil-fired fly ash on mucociliary respiratory epithelium. Two vanadium compounds, VOSO4 and V2O5, and fly ash from an oil-fueled power plant were dissolved or suspended in culture medium over a range of concentrations and epithelia were exposed for 1 hr/day, for 9 consecutive days. At intervals during this period, alterations in cilia-beating frequency, cytology, and histology were documented by light microscopy. Explants treated with VOSO4 either decreased ciliary activity or produced ciliostasis depending upon the concentration and length of exposure. Early morphological alterations consisted of vacuolization of both nuclei and cytoplasm. After multiple exposures, cytology of VOSO4-treated respiratory mucosa was markedly affected. Similar changes were observed in cultures exposed to V2O5; however, the cytotoxicity appeared earlier and was more pronounced. Fly ash-treated explants produced similar biological effects when compared to both vanadium compounds. Thus, the data indicate that the extent of vanadium toxicity depends, at least in part, on the vanadium content of the compound tested, and that exposure to this metal and vanadium-rich fly ash can inhibit normal mucociliary function, a vital clearance mechanism in the respiratory tract.

Animals↗

Inhibition of DNA and protein synthesis and cell division by photoactivated haematoporphyrin derivative in hamster ovary cells.

Experiments were performed on cultured Chinese hamster ovary cells exposed to haematoporphyrin derivative (HpD) plus light, yielding survival rates of 40-100%. [3H]-thymidine, [3H]-tryptophan and [14C]-lysine incorporation were used to quantitate DNA and protein synthesis in surviving cells after exposure. Multiple experiments demonstrated 78% reduction in DNA synthesis during the first day after exposure to 20 micrograms ml-1 HpD plus 1140 Jm-2 light followed by progressive recovery to the normal rate after 4-6 days. Protein synthesis was somewhat less sensitive dropping by 54% initially and fully recovering by day 4. Although this cell line has a normal cycle time averaging approximately 15 h, cell division was rarely observed among lone surviving cells until 72 h after exposure. No inhibition was observed in cells exposed to HpD in the dark. These results indicate that photoactivated HpD has a wide spectrum of reversible nuclear and cytoplasmic effects even at sublethal doses. This is consistent with the notion that clinical photodynamic therapy is not likely to result in chronic morbidity.

Animals↗

The effects of PCBs and dioxins on child health.

BACKGROUND/EXPOSURE: Dioxins and PCBs are highly persistent and highly toxic environmental pollutants which at present are derived mainly from waste incineration and food contamination. They are widespread in nature and pollute human food, including breast milk so that basically all children in Europe are exposed to measurable levels. RESULTS/TOXICITY IN CHILDREN: The toxicity of dioxins and PCBs are well described both from animal studies and from a number of human epidemiological studies including several large cohort studies. Especially developmental exposure has been shown to affect endocrine and cognitive systems negatively. Measurable outcomes include reduced IQ and changed behaviour. Foetotoxic effects with reduced birth weight and increased congenital anomalies such as cleft lip have also been described. Exposure to PCBs and dioxins must be considered also in the context of multiple exposure to several toxins simultaneously or sequentially. CONCLUSION/SUGGESTED ACTION: Some measures aimed at reducing exposure to dioxins have been partly successful in that the dioxin content of breast milk is going down. However, further steps to reduce exposure must be taken. We suggest legislative measures for reducing the re-entry of especially PCBs from waste into the environment. Individual pre-conception counselling is recommended in order to reduce developmental exposure and its consequences. Biomonitoring of the substances themselves in breast milk and foods is recommended as well as monitoring possible endocrine effects.

Child↗

Assessment of exposure in an international study on cancer risks among pulp, paper, and paper product workers.

A data management system and a department-exposure matrix (PAPDEM) was designed and constructed to facilitate exposure assessment for a large multinational study on cancer risks among pulp, paper, and paper product workers. Exposure to 25 major agents was described by prevalence, P (i.e., proportion of the exposed, classified %-range), and level, L (i.e., annual mean concentration at work, classified). Some agents could be assessed only in qualitative terms. The assessment was specific to mill, work department, agent, and time period. The results of industrial hygiene measurements, information from detailed company questionnaires, and the professional judgments of the assessment team were the cornerstones of the assessment. Validity and consistency of the assessment were aimed at by setting default values for P and L prior to the assessment, accurately defining agents and exposure classes, dividing assessment work by subindustry, working in pairs, testing interrater agreement, and finalizing the estimates in a meeting. In spite of these precautions, good agreement between different assessors was difficult to reach. Exposure to chemical agents turned out to be widespread and complex with frequent multiple exposures. A computer-assisted exposure assessment system such as PAPDEM may save time and facilitate assessment in large epidemiological studies requiring complicated exposure assessment procedures. It also provides a good documentation of exposure assignments, which may be useful in the interpretation of the results and in future updates of the study.

Epidemiologic Studies↗

Humoral immune response to a sevoflurane degradation product in the guinea pig following inhalation exposure.

Compound A (2-fluoromethoxy-1,1,3,3,3-pentafluoro-1-propene) is produced by reaction of the inhalation anesthetic, sevoflurane, with CO2 absorbents. Compound A has been reported to directly react with protein. Since adduction of proteins can transform them into antigenic material, Compound A was assessed for its ability to produce a humoral immune response. Male outbred Hartley guinea pigs (500-600 g, N = 7) were exposed via inhalation for 4 h to a subtoxic level (100 ppm) of Compound A, 3 times, at 42 day intervals. Blood samples obtained at 2, 14, 28 and 40 days after each exposure were measured for ALT, creatinine, and urea nitrogen and for the presence of antibodies to trifluoroacetylated guinea pig albumin (TFA-GSA). All indicators of liver and kidney injury remained within normal range throughout the course of the study. A humoral immune response to TFA-GSA was observed following each exposure to Compound A with a titer appearing by day 14 after exposure, peaking near day 28, and resolving to normal levels by day 40. The titer levels were approximately equivalent after each exposure and about one-third that previously seen in guinea pigs after multiple exposures to halothane. Compound A would appear to have the ability to form antigenic adducts during inhalation exposure. These findings are similar to those observed for halogenated inhalation anesthetics that have been linked to cases of immune-medicated idiosyncratic hepatitis and indicate that Compound A exposure may pose the same hazard.

Alanine Transaminase↗

Protective and therapeutic immunity against leukemia induced by irradiated B7-1 (CD80)-transduced leukemic cells.

B7 molecules provide an important costimulatory signal for T cell receptor/CD3-mediated T cell activation via binding to their cognate receptors, CD28 and CTLA-4. We have introduced B7-1 (CD80) into M1 cells, spontaneously-occurred mouse myelocytic leukemic cells and assessed its potential in the induction immunity to leukemia cells. Syngeneic, immunocompetent SL mice receiving polyclonal B7-1-transduced M1 cells showed prolonged survival than control mice. Two independent B7-1-transduced monoclonal sublines, M1-B7-1+ (F20) and M1-B7-1+ (F7), were rejected in 100% an 50% of SL mice, respectively. In vivo depletion of T cell subsets showed that both CD4+ and CD8+ T cells were indispensable for the B7-1-dependent anti-leukemic immunity. Although a single exposure to irradiated monoclonal M1-B7-1+ cells were not fully effective, multiple exposures induced protective immunity against subsequent challenge with M1 cells. Furthermore, hyperimmunization with irradiated monoclonal M1-B7-1+ (F7) cells could partly cure mice previously injected with a lethal number of M1 cells. Although other groups have demonstrated that live, proliferating B7-1-transduced leukemic cells can improve antitumor immunity, this is the first report which shows that irradiated B7-1-transduced myeloid leukemic cells can induce protective and therapeutic immunity against leukemia.

Animals↗

The effect of marijuana smoke exposure on murine sarcoma 180 survival in Fisher rats.

Fisher rats were treated for 28 or 60 days to multiple exposures to the smoke of marijuana or marijuana placebo cigarettes. Primary, secondary and in some instances tertiary tumor implants were performed. Murine sarcoma 180 tumor cells (7.5 x 10(7)) were implanted subcutaneously on day 1, 14 and 28 following initiation of smoke exposure (28 day studies) or on day 1, 14 after cessation of smoke exposure (60 day studies). Tumor areas were measured on alternate days beginning on the second or third day after implantation for 13 or 14 days. Exposure to both marijuana and placebo smoke for 28 days (6, 9 and 18 cigarettes per day) resulted in suppressed growth of secondary and tertiary implants. Administration of delta 9 tetrahydrocannabinol (50 mg/kg, i.p., 20 days) failed to suppress the growth of primary and secondary tumors. This suggests that noncannabinoid constituents of the smoke may contribute to the suppression of tumor growth. Exposure of rats to 9, but not 4 or 6, marijuana or placebo cigarettes per day for 60 days suppressed the growth of primary but not secondary tumors. Thus, the effects of smoke exposure appear to be lost by two weeks after cessation of treatment. The possible existence of a non-cannabinoid immunostimulant in the smoke is discussed.

Animals↗

Single and multiple prenatal glucocorticoid exposures improve preterm newborn lamb cardiovascular and renal function similarly.

OBJECTIVE: Renal and cardiovascular function improves in preterm newborn lambs after a single prenatal betamethasone treatment. We hypothesized that multiple betamethasone exposures would further improve renal and cardiovascular adaptation. STUDY DESIGN: Pregnant ewes were chosen randomly to receive saline solution, one dose of 0.5 mg/kg betamethasone at 104 days of gestation, or three doses of 0.5 mg/kg betamethasone at 104, 111, and 118 days of gestation. Lambs were delivered at 125 days of gestation (preterm) or 145 days of gestation (term). Renal and cardiovascular responses to phenylephrine were evaluated at 2 hours of age. RESULTS: The preterm single and multiple betamethasone-treated lambs comparably increased glomerular filtration rate, urinary flow and osmolar clearance, and sodium excretion in response to phenylephrine. Term responses were similar and not influenced by betamethasone exposure. CONCLUSION: Multiple courses of betamethasone do not further improve renal and cardiovascular responses from a single betamethasone dose. Renal and cardiovascular function at term is not affected by early prenatal betamethasone exposure.

Aldosterone↗