RESUMEN
Iron-containing preparations available on the market vary in dosage, salt, and chemical state of iron contained in the preparation, as well as in the iron delivery process (immediate or prolonged-release). The present study aimed at characterizing the serum pharmacokinetics of iron in non pregnant women with iron deficiency anaemia (IDA) following a single oral administration of a prolonged-release ferrous sulphate tablet. This multicenter, single dose, open-label study was conducted in 30 women aged between 18 and 45 years with IDA. A single 160 mg oral dose of ferrous sulphate was given as 2 tablets of 80 mg of Tardyferon(®) under fasting conditions. Blood samples were collected before dosing and until 24 h post-dosing. Serum iron concentrations were determined using a routine colorimetric analytical method. Pharmacokinetic parameters were determined from the serum concentration profiles using a non compartmental approach. Serum profiles showed elevated levels of iron up to 12 h after drug intake. The median time to maximum serum concentrations (Tmax) occurred 4 h post-dosing. Between 2 and 8 h post-dosing, mean serum iron concentrations fluctuated by only 20%. Additionally, C8h and C12h represented on average 78.6% and 47.5% of the Cmax, respectively. This study demonstrates that a single oral dose of 160 mg Tardyferon(®) administered under fasting condition to 30 women with IDA leads to an optimal long-lasting release of iron in the gastrointestinal tract in the targeted population. This allows the attainment and maintenance of elevated serum iron levels for up to 12 h after administration.
Asunto(s)
Anemia Ferropénica/tratamiento farmacológico , Compuestos Ferrosos/farmacocinética , Compuestos Ferrosos/uso terapéutico , Mucinas/farmacocinética , Mucinas/uso terapéutico , Administración Oral , Adolescente , Adulto , Anemia Ferropénica/metabolismo , Preparaciones de Acción Retardada/farmacocinética , Preparaciones de Acción Retardada/uso terapéutico , Combinación de Medicamentos , Femenino , Humanos , Persona de Mediana Edad , Comprimidos/farmacocinética , Comprimidos/uso terapéutico , Adulto JovenRESUMEN
AIM: The aim of this study was to compare the change in functional signs of venous insufficiency and venous refilling time measured by mercury strain-gauge plethysmography under the effects of the combination of Ruscus aculeatus, hesperidin methylchalcone and ascorbic acid (Cyclo 3 Fort). METHODS: An open-label clinical trial conducted in 65 women presenting with CEAP class C2s and C3s assessment criteria. At D0 and D28, functional signs were measured on a visual analog scale (VAS), venous refilling time by mercury strain-gauge plethysmography and venous reflux by echo-Doppler method. RESULTS: Under treatment, venous refilling time increased from 11.7±4 s to 13.8±4.4 s with Δ of 26% (P<0.0001) and the percentage of patients showing improvement of functional symptoms ≥30% was significantly correlated (P=0.04) with the percentage of patients presenting an improvement in venous refilling time ≥10%. CONCLUSION: Improvement in subjective functional signs under treatment with Cyclo 3 Fort was correlated with objective plethysmographic parameter improvement. There-fore, this study contributes to objectively document the benefit of prescribing this venoactive drug to active women with CEAP class C2s to C3s.
Asunto(s)
Ácido Ascórbico/uso terapéutico , Fármacos Cardiovasculares/uso terapéutico , Chalconas/uso terapéutico , Hesperidina/análogos & derivados , Extractos Vegetales/uso terapéutico , Pletismografía , Ruscus , Insuficiencia Venosa/diagnóstico , Insuficiencia Venosa/tratamiento farmacológico , Actividades Cotidianas , Análisis de Varianza , Distribución de Chi-Cuadrado , Quimioterapia Combinada , Femenino , Francia , Hesperidina/uso terapéutico , Humanos , Valor Predictivo de las Pruebas , Recuperación de la Función , Resultado del Tratamiento , Ultrasonografía Doppler , Insuficiencia Venosa/fisiopatologíaRESUMEN
AIMS: To determine the effects of carbohydrates on Bacillus cereus ATCC14579(T) anaerobic metabolism and enterotoxin production in amino acids rich medium. METHODS AND RESULTS: Bacillus cereus anaerobic growth on different carbohydrates (glucose, fructose, sucrose or glucose-fructose mixture) was examined in synthetic mMOD medium under continuous cultures (mu = 0.2 h(-1)). Fermentation end-products, flux partitioning at each key branch points of the mixed acid pathway and consumption or production of amino acids were determined. On both fructose and sucrose, ATP production was favoured via acetate production from acetyl-CoA. In addition, amino acids present in the growth medium showed significant variations with high consumption of serine and net production of glutamate and alanine on some or all sugars. Enterotoxins Hbl and Nhe production was high during growth on fructose (or mixtures involving a fructose moiety). CONCLUSIONS: Fructose was identified as a key sugar influencing anaerobic metabolism and toxin production of B. cereus. SIGNIFICANCE AND IMPACT OF THE STUDY: The physiological differences associated with the fermentation of the various carbohydrates clearly modify toxinogenesis indicating that the risk of foodborne pathogens is to some extent dependent upon the prevailing nutritional environment.
Asunto(s)
Aminoácidos/metabolismo , Bacillus cereus/efectos de los fármacos , Carbohidratos/farmacología , Enterotoxinas/biosíntesis , Adenosina Trifosfato/metabolismo , Alanina/metabolismo , Bacillus cereus/genética , Bacillus cereus/crecimiento & desarrollo , Bacillus cereus/metabolismo , Medios de Cultivo/química , Medios de Cultivo/farmacología , Fermentación , Fructosa/metabolismo , Fructosa/farmacología , Glucosa/metabolismo , Glucosa/farmacología , Ácido Glutámico/metabolismo , Reacción en Cadena de la Polimerasa/métodos , ARN Bacteriano/genética , ARN Ribosómico 16S/genética , Serina/metabolismoRESUMEN
AIMS: To determine the effects of porcine bile (PB) on Bacillus cereus vegetative cells and Haemolysin BL (HBL) enterotoxin production in reconstituted small intestine media (IM). METHODS AND RESULTS: The effects of PB on the growth of B. cereus vegetative cells in reconstituted IM at PB concentrations ranging between 0 and 3.0 g l(-1) were examined. Four gastric media (GM) named GM-J broth (JB), GM-chicken, GM-milk and GM-pea were prepared by mixing equal volumes of a gastric electrolyte solution containing pepsin with JB, chicken, semi-skimmed milk and pea soup, respectively. Bacillus cereus was inoculated at approx. 2 x 10(4) CFU ml(-1) into each GM at pH 5.0 for 30 min at 37 degrees C, then mixed to the same volume of double-strength JB (IM) and PB to give concentrations of between 0 and 3.0 g of PB per litre at pH 6.5 and incubated at 37 degrees C. The diarrhoeal B. cereus strain F4430/73 grew in IM-JB, IM-chicken and IM-milk at PB concentrations of up to 0.6, 1.5 and 1.2 g l(-1), respectively. Growth was observed in IM-pea at all concentrations tested. The highest PB concentrations allowing a 3 log B. cereus increase in IM-JB, IM-chicken, IM-milk and IM-pea after a 7-10 h incubation period were 0.3, 0.9, 0.9 and 3.0 g l(-1), respectively. The effect of PB on B. cereus cells was strongest in IM-JB, followed by IM-chicken, IM-milk and IM-pea. Haemolysin BL enterotoxin was detectable in IM-chicken, IM-whole milk, IM-semi-skimmed milk and IM-pea up to PB concentrations of only 0.6, 0.6, 0.3 and 0.9 g l(-1), respectively. The diarrhoeal B. cereus strain F4433/73 behaved similarly to B. cereus strain F4430/73, whereas the food strain TZ415 was markedly more susceptible to bile. CONCLUSIONS: The tolerance of B. cereus cells to PB strongly depends on the type of food contained in the IM. Bile tolerance is also subject to strain variation. SIGNIFICANCE AND IMPACT OF THE STUDY: The probability that B. cereus cells will grow in the small intestine, produce toxins and cause diarrhoea is likely to depend on the food they are ingested with, on the bile tolerance of the B. cereus strain, and on bile concentration.
Asunto(s)
Infecciones por Bacillaceae/microbiología , Bacillus cereus/fisiología , Proteínas Bacterianas/biosíntesis , Ácidos y Sales Biliares/farmacología , Microbiología de Alimentos , Enfermedades Transmitidas por los Alimentos/microbiología , Proteínas Hemolisinas/biosíntesis , Animales , Bacillus cereus/efectos de los fármacos , Proteínas Bacterianas/análisis , Técnicas Bacteriológicas , Recuento de Colonia Microbiana , Proteínas Hemolisinas/análisis , Humanos , Concentración de Iones de Hidrógeno , Intestino Delgado/microbiología , Pruebas de Sensibilidad Microbiana , Viabilidad Microbiana/efectos de los fármacos , PorcinosRESUMEN
AIMS: To determine the fate of Bacillus cereus spores or vegetative cells in simulated gastric medium. METHODS AND RESULTS: The effects of acidity on the survival of B. cereus in a medium simulating human stomach content was followed on spores at pH 1.0-5.2, and on vegetative cells at pH 2.5-5.7. Gastric media (GM) were prepared by mixing equal volumes of a gastric electrolyte solution with J broth (JB), half-skim milk, pea soup and chicken. At pH 1.0 and 1.4, the number of spores slightly decreased in GM-JB and GM-pea soup and remained stable in GM-milk and GM-chicken. A rapid marked decrease (always higher than 2.0 log CFU ml(-1) in 2 h) in vegetative cell counts was observed at pH below 4.2, 4.0, 3.6 and 3.5 in GM-chicken, GM-JB, GM-milk and GM-pea soup, respectively. Between pH 5.0 and 5.3, B. cereus growth was observed in GM-JB (1.2 log CFU ml(-1) increase after 4 h) and in GM-pea soup (1.8 log CFU ml(-1) increase after 4 h). CONCLUSIONS: Bacillus cereus spores are very much more resistant to gastric acidity than vegetative cells. This resistance strongly depends on the type of food present in the GM. SIGNIFICANCE AND IMPACT OF THE STUDY: Our results suggest that the probability that viable B. cereus cells enter the small intestine, where they can cause diarrhoea, strongly depends on the form of the ingested cells (spores or vegetative cells), on what food they are ingested with, and on the level of stomach acidity.
Asunto(s)
Bacillus cereus/fisiología , Microbiología de Alimentos , Ácido Gástrico , Técnicas Bacteriológicas , Humanos , Concentración de Iones de Hidrógeno , Modelos Biológicos , Esporas BacterianasRESUMEN
OBJECTIVE: A mortality study on the association between lung cancer and occupational exposure to polycyclic aromatic hydrocarbons (PAHs) was carried out in a French aluminium reduction plant. This study updated a previous mortality study. METHOD: The historical cohort included every male worker who had been employed in the plant for at least 1 year between 1950 and 1994. Workers were followed-up for mortality from 1968 to 1994. Causes of death were obtained from death certificates. Standardised mortality ratios (SMRs) and 95% confidence intervals (CI) were computed using regional mortality rates as external reference to compare observed and expected numbers of deaths, adjusted for gender, age and calendar time. RESULTS: The cohort comprised 2,133 men, of whom 335 died during the follow-up period. The observed mortality was lower than expected for all causes of death (SMR = 0.81, CI 0.72-0.90) and for lung cancer (observed = 19, SMR = 0.63, CI 0.38 0.98). No lung cancer excess was observed in workshops where PAH exposure was likely to have occurred, and no trend was observed according to duration of exposure and time since first exposure. This low lung cancer mortality could be partly explained by a marked healthy worker effect and a possible negative confounding by smoking. An excess was observed for bladder cancer (observed = 7, SMR = 1.77, CI 0.713.64) in the whole cohort, that was higher among workers employed in workshops where PAH exposure was likely to have occurred (observed = 6, SMR = 2.15, CI 0.79-4.68). In addition, an SMR higher than unity was observed for "psychoses and neuro-degenerative diseases" (observed = 6, SMR = 2.39, CI 0.88-5.21), that could not be related to occupational aluminium exposure. CONCLUSION: No lung cancer risk was detected. Non-significant excesses were observed for bladder cancer and for psychoses and neuro-degenerative diseases.
Asunto(s)
Neoplasias Pulmonares/mortalidad , Metalurgia , Exposición Profesional/efectos adversos , Hidrocarburos Policíclicos Aromáticos/efectos adversos , Anciano , Anciano de 80 o más Años , Aluminio , Enfermedad de Alzheimer/etiología , Enfermedad de Alzheimer/mortalidad , Causas de Muerte , Estudios de Seguimiento , Francia/epidemiología , Humanos , Neoplasias Pulmonares/etiología , Masculino , Mortalidad , Fumar/efectos adversos , Neoplasias de la Vejiga Urinaria/etiología , Neoplasias de la Vejiga Urinaria/mortalidadRESUMEN
OBJECTIVES: The mortality of workers involved in the production of stainless and alloyed steel from 1968 to 1992 was studied, in order to investigate the risk of lung cancer due to exposure to metals, i.e. iron oxides, chromium and/or nickel compounds. METHODS: The study design was a historical cohort mortality study and a nested case-control study concerning lung cancer. Standardized mortality ratios (SMRs) were computed using regional mortality rates as an external reference for comparing observed and expected numbers of deaths, adjusting for age, sex and calendar time. Conditional logistic regression was used to estimate odds ratios (ORs). Occupational exposure was assessed through the complete job histories of cases and controls and a specific job-exposure matrix. RESULTS: The cohort comprised 4,288 male and 609 female workers. The observed overall mortality was significantly lower than expected [649 deaths; SMR = 0.91; 95% confidence interval (CI) 0.84-0.98]. No significant SMR was observed for mortality from lung cancer (54 deaths; SMR = 1.19; CI 0.88-1.55). The case-control study was based on 54 cases and 162 individually matched controls. Smoking habits were available for 71%. No lung cancer excess was observed for exposure to (1) metals and/or their compounds, i.e. iron (OR = 0.94, CI 0.48-1.86), chromium and/or nickel (OR = 1.18, CI 0.62-2.25), and cobalt (OR =0.64, CI 0.33-1.25), (2) acid mists (OR = 0.43, CI 0.17-1.10), and (3) asbestos (OR = 1.00, CI 0.54-1.86). With respect to exposure to polycyclic aromatic hydrocarbons (PAHs) and silica, which are often found together in workplaces, (1) high and statistically significant lung cancer excesses were observed, the ORs being 1.95 (CI 1.03-3.72) and 2.47 (CI 1.28-4.77) respectively, (2) quantitative exposure parameters revealed upward trends reaching statistical significance (P < 0.05), and (3) adjustments for tobacco consumption did not reveal any confounding factors from smoking. CONCLUSION: This study failed to detect any relationship between lung cancer and exposure to iron, chromium, nickel and/or their compounds. High and statistically significant relative risks, along with increasing trends, were observed for simultaneous exposure to PAHs and silica.
Asunto(s)
Aleaciones/efectos adversos , Neoplasias Pulmonares/epidemiología , Metalurgia , Enfermedades Profesionales/epidemiología , Acero/efectos adversos , Anciano , Contaminantes Atmosféricos/efectos adversos , Estudios de Casos y Controles , Estudios de Cohortes , Femenino , Francia/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Compuestos Policíclicos/efectos adversos , Factores de Riesgo , Dióxido de Silicio/efectos adversosRESUMEN
The Tol-Pal proteins of Escherichia coli are involved in maintaining outer membrane integrity. They form two complexes in the cell envelope. Transmembrane domains of TolQ, TolR, and TolA interact in the cytoplasmic membrane, while TolB and Pal form a complex near the outer membrane. The N-terminal transmembrane domain of TolA anchors the protein to the cytoplasmic membrane and interacts with TolQ and TolR. Extensive mutagenesis of the N-terminal part of TolA was carried out to characterize the residues involved in such processes. Mutations affecting the function of TolA resulted in a lack or an alteration in TolA-TolQ or TolR-TolA interactions but did not affect the formation of TolQ-TolR complexes. Our results confirmed the importance of residues serine 18 and histidine 22, which are part of an SHLS motif highly conserved in the TolA and the related TonB proteins from different organisms. Genetic suppression experiments were performed to restore the functional activity of some tolA mutants. The suppressor mutations all affected the first transmembrane helix of TolQ. These results confirmed the essential role of the transmembrane domain of TolA in triggering interactions with TolQ and TolR.
Asunto(s)
Proteínas Bacterianas/genética , Proteínas de Escherichia coli , Escherichia coli/genética , Proteínas de la Membrana/genética , Supresión Genética , Secuencia de Aminoácidos , Proteínas Bacterianas/metabolismo , Sitios de Unión , Escherichia coli/metabolismo , Proteínas de la Membrana/metabolismo , Datos de Secuencia Molecular , MutagénesisRESUMEN
The Tol-Pal proteins of Escherichia coli are involved in maintaining outer membrane integrity. Transmembrane domains of TolQ, TolR and TolA interact in the cytoplasmic membrane, while TolB and Pal form a complex near the outer membrane. TolB and the central domain of TolA interact in vitro with the outer membrane porins. In this study, both genetic and biochemical analyses were carried out to analyse the links between TolB, Pal and other components of the cell envelope. It was shown that TolB could be cross-linked in vivo with Pal, OmpA and Lpp, while Pal was associated with TolB and OmpA. The isolation of pal and tolB mutants disrupting some interactions between these proteins represents at first approach to characterizing the residues contributing to the interactions. We propose that TolB and Pal are part of a multiprotein complex that links the peptidoglycan to the outer membrane. The Tol-Pal proteins might form transenvelope complexes that bring the two membranes into close proximity and help some outer membrane components to reach their final destination.
Asunto(s)
Proteínas de la Membrana Bacteriana Externa/metabolismo , Proteínas Bacterianas/metabolismo , Proteínas Portadoras/metabolismo , Proteínas de Escherichia coli , Escherichia coli/metabolismo , Lipoproteínas/metabolismo , Proteínas de la Membrana/metabolismo , Peptidoglicano/metabolismo , Proteínas Periplasmáticas , Proteoglicanos , Secuencia de Aminoácidos , Proteínas de la Membrana Bacteriana Externa/biosíntesis , Proteínas de la Membrana Bacteriana Externa/genética , Proteínas Bacterianas/genética , Reactivos de Enlaces Cruzados , Escherichia coli/genética , Lipoproteínas/genética , Datos de Secuencia Molecular , Mutagénesis , Peptidoglicano/genética , Homología de Secuencia de AminoácidoRESUMEN
OBJECTIVE: After an inquiry from the employees of an offset printing plant, a historical cohort study was conducted to investigate cancer mortality among these workers. METHODS: The cohort comprised 262 men, who contributed 2771 person-years of observation. 16 deaths were identified during the follow up period (1980-91). Expected numbers of deaths were derived from age specific regional rates. Standardised mortality ratios (SMR) and 95% confidence intervals (95% CIs) were calculated. RESULTS: An increased cancer mortality was found after 10 years of employment (SMR 213, 95% CI 98 to 405, based on nine deaths), mainly due to a high mortality from lung cancer (SMR 381, 95% CI 104 to 975, four deaths), and from oesophageal cancer (SMR 1049, 95% CI 216 to 3065, three deaths). For workers with at least 20 years since the start of employment, the SMR was 262 (95% CI 105 to 540) for all cancer sites, 447 (95% CI 92 to 1306) for lung cancer, and 1094 (95% CI 132 to 3952) for oesophageal cancer. The increased cancer mortality was concentrated among pressmen. CONCLUSION: Although based on small numbers, the findings suggest an increased risk of cancer among these workers, which should be further investigated.
Asunto(s)
Neoplasias/mortalidad , Enfermedades Profesionales/mortalidad , Impresión , Estudios de Cohortes , Neoplasias Esofágicas/mortalidad , Humanos , Neoplasias Pulmonares/mortalidad , Masculino , Oportunidad Relativa , Estudios RetrospectivosRESUMEN
The TolQ, TolR, TolA, TolB, and Pal proteins appear to function in maintaining the integrity of the outer membrane, as well as facilitating the uptake of the group A colicins and the DNA of the infecting filamentous bacteriophages. Sequence data showed that these genes are clustered in a 6-kb segment of DNA with the gene order orf1 tolQ tolR tolA tolB pal orf2 (a newly identified open reading frame encoding a 29-kD9 protein). Like those containing orf1, bacteria containing an insertion mutation in this gene showed no obvious phenotype. Analysis of beta-galactosidase activity from fusion constructs in which the lac operon was fused to various genes in the cluster showed that the genes in this region constitute two separate operons: orf1 tolQRA and tolB pal orf2. In the orf1 tolQRA operon, translation of MR was dependent on translation of the upstream tolQ region. Consistent with this result, no functional ribosome-binding site for TolR synthesis was detected.
Asunto(s)
Proteínas Bacterianas/genética , Proteínas de Escherichia coli , Escherichia coli/genética , Regulación Bacteriana de la Expresión Génica , Proteínas de la Membrana/genética , Biosíntesis de Proteínas , Secuencia de Aminoácidos , Proteínas Bacterianas/metabolismo , Secuencia de Bases , Clonación Molecular , Prueba de Complementación Genética , Proteínas de la Membrana/metabolismo , Datos de Secuencia Molecular , Mutagénesis Insercional , Sistemas de Lectura Abierta , Operón , Homología de Secuencia de Aminoácido , Especificidad de la Especie , Transcripción GenéticaRESUMEN
The tolQRABpal cluster of Escherichia coli K-12 encodes proteins involved in the maintenance of cell-envelope integrity. In addition, tol/pal mutations result in a mucoid colony phenotype at low temperature. The synthesis of capsular polysaccharides by the cps genes is controlled by the positive regulator RcsA and the two-component RcsC/RcsB system. It was shown that the mucoid phenotype of the tol/pal mutants was due to an rcsCB-dependent activation of the cps genes. Furthermore, we have identified a mutation in the rcsC gene that decreased the activity of a tolA-lac operon fusion independently of RcsA and partially independently of RcsB activators. The corresponding rcsC338 mutation resulted in a Glu to Lys substitution at residue 338 of RcsC. This mutation induced mucoidy even at high temperature. We propose that RcsC modulates the phosphorylated forms of RcsB and an uncharacterized regulatory protein involved in the control of the tolQRA genes in an opposite manner. Moreover, our findings strengthen the previous suggestion that RcsC senses some alterations in the cell surface such as those induced by tol, pal or rfa mutations, and activates capsule synthesis to protect the cell against deleterious agents.
Asunto(s)
Cápsulas Bacterianas/biosíntesis , Proteínas Bacterianas/metabolismo , Proteínas de Escherichia coli , Escherichia coli/metabolismo , Regulación Bacteriana de la Expresión Génica/genética , Complejos Multienzimáticos , Fosfoproteínas Fosfatasas , Proteínas Quinasas , Factores de Transcripción/metabolismo , Alelos , Proteínas Bacterianas/genética , División Celular , Clonación Molecular , Operón Lac/genética , Fenotipo , Mutación Puntual/genética , Temperatura , Factores de Transcripción/genética , beta-Galactosidasa/genética , beta-Galactosidasa/metabolismoRESUMEN
A mortality study was carried out in two factories producing stainless steel in order to assess lung cancer risk among workers employed in coke oven, blast and open hearth furnaces, foundry, electric furnace, hot and cold rolling mills and pickling areas. Occupational exposures of interest were chromium compounds, nickel compounds, polycyclic aromatic hydrocarbons (PAH), silica and asbestos. All male workers having at least one year of employment between 01.01.1960 and 31.12.1990 were followed up for mortality. The vital status was assessed from birth place registries. Complete job histories since date of first employment were abstracted from the company files. The smoking habits of 50% of the cohort members were known from medical records. The observed number of deaths (obs) were compared with the expected ones based on regional rates with adjustment for age, sex and calendar time (Standardized Mortality Ratio, SMR). The cohorts included 6324 (factory 1) and 5270 (factory 2) workers. The overall mortality did not differ markedly from that expected in both factories: SMR = 0.95 (obs = 1540, p = 0.05) in factory 1 and SMR = 1.06 (obs = 916, non-significant) in factory 2. SMRs for lung cancer did not differ from unity, respectively 0.99 (obs = 105) and 1.00 (obs = 54), in whole cohorts. Non-significant lung cancer excesses were observed among workers of some workshops where exposures of interest might have occurred: coke oven (SMR = 2.04), blast furnace (SMR = 1.36), open hearth furnace (SMR = 1.75), hot rolling mills (SMR = 1.29). These processes, however, are no longer involved in the study factories. Furthermore, no lung cancer excess was observed among workers employed in current workshops: electric furnaces and cold rolling mills.
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Neoplasias de los Bronquios/mortalidad , Neoplasias Pulmonares/mortalidad , Metalurgia , Enfermedades Profesionales/mortalidad , Adulto , Amianto/efectos adversos , Neoplasias de los Bronquios/inducido químicamente , Neoplasias de los Bronquios/etiología , Causas de Muerte , Compuestos de Cromo/efectos adversos , Estudios de Cohortes , Humanos , Neoplasias Pulmonares/inducido químicamente , Neoplasias Pulmonares/etiología , Masculino , Persona de Mediana Edad , Níquel/efectos adversos , Exposición Profesional , Compuestos Policíclicos/efectos adversos , Fumar , Acero Inoxidable , Factores de TiempoRESUMEN
This study has been conducted to clarify certain issues regarding residency training with regard to acquired immunodeficiency syndrome (AIDS). The objective was to evaluate resident physicians' experiences in, and attitudes toward, the care of persons with AIDS in France. The design was a cross sectional study, using a self administered mailed questionnaire to 627 residents in 3 French areas: Ile-de-France, Nord-Pas de Calais and Province-Côte d'Azur, with a follow up of non responders. The subjects of this study were a random sample of residents in the second year of specialty medicine or family medicine residencies (biological residents, surgeons, public health residents and research residents were excluded). The response rate was 56%. More than half of residents indicated that their training was deficient in AIDS ambulatory care and less of 40% felt competent to provide usual and primary care for AIDS patients. The social and psychosocial aspect of care seems to be the greatest difficulties for them. About the half of residents reported at least one needle stock contaminated by a patient's blood. Needle stick injuries from patients known to have HIV infection were reported by 8% of them. About 25% expressed great concern about the professional risk of HIV contamination and 24% indicated it is dangerous to provide care for AIDS patients. It appears that an important component of future education in medical residency programs should emphasize strategies to address social and psychosocial issues in the medical care of AIDS patients and to decrease the risk of needle stick injuries.
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Síndrome de Inmunodeficiencia Adquirida , Actitud del Personal de Salud , Actitud Frente a la Salud , Internado y Residencia , Accidentes de Trabajo , Adulto , Estudios Transversales , Femenino , Francia , Humanos , Masculino , Lesiones por Pinchazo de Aguja/etiología , Factores de Riesgo , Encuestas y CuestionariosRESUMEN
Recent findings have indicated that megakaryocytes may be susceptible to human immunodeficiency virus (HIV) infection, suggesting a potential role for megakaryocytes as viral reservoirs in HIV-infected patients. We report that the megakaryocytic cell line Dami could be productively infected with the HTLV III-B strain of HIV-1, in 26 different experiments (results of 16 experiments are reported); productive infection lasted up to 30 weeks. Despite a lack of detectable surface expression of the CD4 molecule and very low levels of CD4 mRNA, between 40% and 60% of megakaryocytic cells produced viral proteins after contact with HIV-1. Neither cytopathogenic effects nor syncytial formation was observed. Production of high levels of functional viral particles was indicated by analysis of p24 protein levels, reverse transcriptase activity, ultrastructural studies, and the capacity of supernatants from infected Dami cells to infect the Molt-4 T-lymphocytic cell line. HIV-1 RNA and protein levels in infected Dami cells were enhanced by treatment with tumor necrosis factor-alpha (TNF-alpha), and decreased by treatment with interferon-alpha (IFN-alpha) and IFN-gamma. Transient transfection of the megakaryocytic cells with various constructs of the HIV-1 promoter (LTR) linked to the luciferase reporter gene suggested that the effect of TNF-alpha was related, as in monocytic and T-cell lines, to transactivation of the enhancer region of the HIV-1 LTR. These findings indicate that signals provided by the immune system may modulate HIV-1 expression in cells of the megakaryocytic lineage.