RESUMEN
BACKGROUND: Continued employment of people with health problems that reduce their ability to work is a major social issue. The French measures to optimize job retention are characterized by a multiplicity of participants, and their efficacy depends largely on the capacity of these different participants to work together. The objective of this study was to document the perceived role, attitudes and practices of participants involved in these job retention measures and of general practitioners, as well as their difficulties in this domain. METHODS: In 2009, 15 semi-directive interviews were conducted in the region of Provence-Alpes-Côte d'Azur (PACA) of occupational physicians, general practitioners, and other participants involved in the occupational reclassification of workers no longer completely fit for their job. The data collected were analyzed from a thematic perspective. RESULTS: The different groups of professionals questioned agreed on the primacy of the role of the occupational physician, on the importance of early consideration of each worker's case, and on the need to work together as partners to optimize the prospects of job retention. This study nonetheless showed numerous communication difficulties between the various professionals: although informal exchanges have developed over time, the efficacy of the system seems to be limited by a lack of clarity about the role of each institution, divergences of opinions on some key points including the role of the physicians caring for the patient, and, more largely, lack of information about the tools for job retention. CONCLUSION: The distribution of homogeneous knowledge, the development of multidisciplinary collaborative practices and the pooling of the lessons of experience between the different groups of participants are essential for the success of job retention procedures.
Asunto(s)
Actitud del Personal de Salud , Enfermedad Crónica , Empleo/psicología , Médicos/psicología , Pautas de la Práctica en Medicina , Comunicación , Francia , Médicos Generales/psicología , Humanos , Salud Laboral , Medicina del Trabajo , Grupo de Atención al Paciente , Rol del MédicoRESUMEN
PURPOSE: Physicians can play an important role in the reporting of occupational diseases (ODs), which are still under-reported in many countries. We aimed to identify physicians' difficulties in recognizing and reporting ODs and to study the characteristics of the physicians that do report ODs. METHODS: We conducted a telephone study in 2006-2007 among general practitioners (GPs), pulmonologists and rheumatologists in south-eastern France, concerning their knowledge, attitudes and practice in occupational health. Simple and multiple logistic regressions were performed to study factors associated with the issue of medical certificates for the claim process. RESULTS: Three hundred and ninety-one GPs, 95 pulmonologists and 96 rheumatologists participated. GPs reported significantly less often than specialists that they questioned their patients on past occupational exposure. They more frequently reported difficulties in identifying the occupational origin of diseases, and lack of knowledge on the OD reporting system. Issue of medical certificates for OD reporting was significantly more frequent among specialists than among GPs, among physicians considering that ODs are a public health problem, among those acquainted with the forms required to establish certificates, using internet to obtain information, having trade union activities, or having contact with occupational physicians (OPs). CONCLUSION: Initial and continuing training should be developed to encourage physicians, in particular GPs, to question patients on their working conditions and to become better acquainted with claim procedures. Physicians should also be provided with tools for identification of ODs that are suited to their practices, and collaboration with OPs should be fostered.
Asunto(s)
Conocimientos, Actitudes y Práctica en Salud , Notificación Obligatoria , Enfermedades Profesionales/diagnóstico , Médicos de Familia , Neumología , Reumatología , Análisis de Varianza , Estudios Transversales , Femenino , Francia/epidemiología , Humanos , Entrevistas como Asunto , Masculino , Enfermedades Profesionales/epidemiología , Encuestas y CuestionariosRESUMEN
BACKGROUND: A qualitative study was conducted in 2008 of occupational physicians (OPs) in south-eastern France to document their attitudes, opinions and practices on prevention and screening of occupational cancers. This was done to provide elements to prepare the questionnaire of a quantitative study in 2009. METHODS: Semi-structured interviews were conducted using a structured interview guide with 20 OPs. The data collected were subjected to an analysis of thematic content type. RESULTS: The analysis revealed that OPs face many difficulties when preventing occupational cancers. For most of OPs, these difficulties appeared related to "external factors": lack of involvement of employers and minimization of risks by employers and employees. Lack of time, overload and, for some OPs, perceived lack of independence towards employers, were also mentioned as barriers to cancer prevention. This study also suggested hypotheses related to OPs themselves (internal factors): perceived lack of effectiveness and, trend to minimize the risks of occupational cancer in their geographical area. Finally, the results suggest a significant heterogeneity of OPs' practices regarding occupational cancer screening. CONCLUSION: These results raise several hypotheses that will be addressed further in the quantitative survey. They warn about the difficulties of a profession that seems to encounter a demographic and identity crisis.
Asunto(s)
Actitud del Personal de Salud , Neoplasias/prevención & control , Enfermedades Profesionales/prevención & control , Medicina del Trabajo , Femenino , Francia , Humanos , Masculino , Rol del Médico , Pautas de la Práctica en MedicinaRESUMEN
INTRODUCTION: Identifying patients with psychological stress at work (PSW) and managing them are complex tasks. We studied the frequency of PSW as perceived by general practitioners (GPs), their practices in such situations, and the factors associated with these perceptions and practices, especially drug prescription. METHODS: Cross-sectional telephone study of GPs in southeastern France with a questionnaire about knowledge, attitudes, behavior, and practices in occupational health. We explored the management of PSW with a case-vignette of a 45-year-old supermarket cashier consulting for psychological stress that he or she attributes to the job. RESULTS: In all, 391 GPs participated; 87.2% reported that they encountered PSW often in their practice. GPs reported that they would treat the case-vignette patient by prescribing anxiolytics (66.5%) or sick leaves (65.7%) or referral to an occupational physician (80.3%) or a mental health specialist (44.8%). A multiple logistic regression showed that GPs reported prescribing an anxiolytic most frequently for the vignette-patient when they saw a high number of patients daily, asked patients about working conditions, suggested a sick leave or a referral to a specialist to the case-vignette patient and perceived more obstacles to reporting an occupational disease. CONCLUSION: Our study suggests that PSW is perceived by GPs as one of the principal work-related health problems and that in such situations, most GPs say they would prescribe drugs and sick leave and refer the patient to an occupational physician. Initial and continuing education programs and good practice guidelines would be useful to help them deal with these problems.
Asunto(s)
Exposición Profesional/efectos adversos , Salud Laboral/estadística & datos numéricos , Relaciones Médico-Paciente , Médicos de Familia/estadística & datos numéricos , Estrés Psicológico/tratamiento farmacológico , Adaptación Psicológica , Ansiolíticos/uso terapéutico , Estudios Transversales , Femenino , Francia , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Psicometría , Encuestas y CuestionariosRESUMEN
OBJECTIVES: To study physician barriers to workers' compensation claims for asbestos-related cancers, focusing on smokers' stigma and physicians' speciality and role perception. METHODS: Cross-sectional telephone study of 486 randomly-selected general practitioners (GPs) and pulmonologists in south-eastern France. Standardised questionnaires explored their behaviour, attitudes and practices in the field of occupational health and their responses to a case vignette of a lung cancer patient with long-term occupational asbestos exposure. Randomised subgroups of GPs and pulmonologists heard alternative versions varying only as regards the worker's smoking status. We studied factors associated with the recommendation that the case vignette patient file a compensation claim with simple and multiple logistic regressions. RESULTS: The response rate was 64.4% among GPs and 62.5% among pulmonologists. Recommending the filing of an occupational disease claim was significantly associated in multiple logistic regressions with speciality (OR 4.46; 95% CI 2.38 to 8.37, for pulmonologists vs GPs), patient's smoking status (OR 3.15; 95% CI 2.11 to 4.70, for non-smokers vs smokers), physician's workload (OR 1.83; 95% CI 1.17 to 2.88, for 25) and role perception (OR 2.00; 95% CI 1.22 to 3.27, for those who considered completing occupational disease medical certificates to be part of their role vs those who did not). CONCLUSIONS: The results of this French study appear applicable to various countries and contexts. To make physicians and especially GPs more aware of occupational health and smoking stigma, officials and educators must give these topics higher priority during initial training and continuing medical education. Tools and equipment that take time constraints into account should be developed and disseminated to help physicians manage occupational diseases.
Asunto(s)
Amianto/toxicidad , Actitud del Personal de Salud , Neoplasias Pulmonares/etiología , Enfermedades Profesionales/etiología , Fumar/psicología , Indemnización para Trabajadores , Estudios Transversales , Femenino , Francia , Humanos , Masculino , Medicina , Rol del Médico , Médicos de Familia/psicología , Fumar/efectos adversos , Especialización , Carga de TrabajoRESUMEN
BACKGROUND: Occupational health is a major public health problem in France. However, the level of investment of general practitioners and specialist physicians in this field is not well documented. We aimed at studying elements moving closer or differentiating groups of professionals (notably physicians) in the field of occupational health in terms of conceptions of their roles (prevention and care) and of practices (in particular detection and notification of occupational diseases and perceived barriers). METHODS: We conducted a qualitative study in south-eastern France which consisted of in-depth interviews of physicians and actors involved in the prevention of occupational hazards or in their indemnification. Then discourse analysis was carried out on the corpus collected. Content analysis grouped the data into themes. RESULTS: Several reasons could explain the low investment of physicians in the field of occupational health: insufficient detection of occupational causes of diseases, complexity of administrative procedures of declaration and bias of causal interpretation for the patients exposed to other risk factors such as smoking. The fear that notifying an occupational disease might have repercussions on patients' socio-professional situations places physicians in a situation of ethical dilemma: inducing a social risk on one side, ignoring his rights on the other. Physicians are not sufficiently prepared to deal with these situations, because they lack appropriate knowledge and support from specialists in the field, due to an important bulk-heading of actors and their practices. CONCLUSION: To sensitize and train physicians to occupational health and to support multi-field practices are essential.
Asunto(s)
Actitud del Personal de Salud , Actitud Frente a la Salud , Salud Laboral , Médicos , Educación Médica , Ética Médica , Medicina Familiar y Comunitaria , Francia , Humanos , Medicina , Enfermedades Profesionales/diagnóstico , Enfermedades Profesionales/etiología , Enfermedades Profesionales/prevención & control , Medicina del Trabajo/educación , Derechos del Paciente , Rol del Médico , Factores de Riesgo , Fumar , Medio Social , EspecializaciónRESUMEN
PURPOSE: The objective was to estimate the psychometric properties of the Modified-Modified Schober Test (MMST). DESIGN: This study compared range of motion measurements of lumbar flexion in low back pain (LBP) patients using the MMST with measurements calculated on X-rays as the gold standard, and compared the measurements taken by two independent examiners. METHOD: This study was conducted at the main hospital in the Outaouais area, Quebéc, Canada. Thirty-one subjects with LBP from private and public clinics participated in the study. After a warm-up session, measurements with the MMST were taken in neutral position and an X-ray technician took an exposure in the same position. RESULTS: Pearson's correlation test (r) between measurements made with the MMST and the gold standard, intra-class correlation coefficient (ICC), minimum metrically detectable change (MMDC) and confidence interval (CI) were used to analyze the data. The MMST demonstrated moderate validity (r=0.67; 95%CI 0.44-0.84), excellent reliability (intra: ICC=0.95; 95%CI 0.89-0.97; inter: ICC=0.91; 95%CI 0.83-0.96) and a MMDC of 1 cm. CONCLUSIONS: In our sample of LBP patients, the MMST showed moderate validity but excellent reliability and MMDC.
Asunto(s)
Evaluación de la Discapacidad , Dolor de la Región Lumbar/diagnóstico , Región Lumbosacra/fisiopatología , Modalidades de Fisioterapia , Rango del Movimiento Articular , Adulto , Femenino , Humanos , Dolor de la Región Lumbar/diagnóstico por imagen , Dolor de la Región Lumbar/fisiopatología , Masculino , Variaciones Dependientes del Observador , Radiografía , Reproducibilidad de los ResultadosRESUMEN
The preclinical safety of RPR 106541, a novel 17-thiosteroid, was evaluated in young adult and mature dogs by inhalation exposure for 26 weeks and 52 weeks, respectively. A dry powder formulation of RPR 106541 in lactose was administered to young adult dogs (approximately 6 months of age at initiation) at doses of 0 (air and placebo controls), 10, 100, or 1,000 microg/kg/d for 26 weeks. A solution-based aerosol formulation was administered to mature dogs (approximately 10 months at initiation) from a pressurized metered dose inhaler at 0 (air and placebo controls), 10, 50, and 150 microg/kg/d for 52 weeks. Clinical evidence of glucocorticosteroid-induced immunosuppression was observed by weeks 20-26 following relatively high dose exposures (100 microg/kg/d and 1,000 microg/kg/d) in young dogs receiving the dry powder formulation for 26 weeks. Classic glucocorticosteroid effects were observed, including adrenocortical atrophy, reduced bone mass with retention of epiphyseal growth plates in long bones, prominence of stromal adipose tissue in bone marrow, and atrophy of lymphoid tissues. Inhalation administration of RPR 106541 to sexually mature dogs facilitated more definitive characterization of endocrine affects of RPR 106541 as compared with administration in younger, sexually immature animals. Significant effects in female reproductive organs included absence of corpora lutea in association with atresia of vesicular follicles within the ovaries, endometrial hyperplasia, and lobular development of mammary tissue. Discordant development of mammary tissue, accumulation of secretory material within hyperplastic endometrial glands, and hypertrophy of uterine lining epithelium in absence of ovulation were consistent with a secondary progestin effect by a potent glucocorticosteroid.
Asunto(s)
Androstenos/toxicidad , Antiasmáticos/toxicidad , Administración por Inhalación , Glándulas Suprarrenales/efectos de los fármacos , Glándulas Suprarrenales/patología , Aerosoles , Animales , Peso Corporal/efectos de los fármacos , Médula Ósea/efectos de los fármacos , Médula Ósea/patología , Pruebas de Química Clínica , Perros , Femenino , Fémur/efectos de los fármacos , Fémur/patología , Gónadas/efectos de los fármacos , Gónadas/patología , Hígado/efectos de los fármacos , Hígado/patología , Tejido Linfoide/efectos de los fármacos , Tejido Linfoide/patología , Masculino , Glándulas Mamarias Animales/efectos de los fármacos , Glándulas Mamarias Animales/patología , Nebulizadores y Vaporizadores , Tamaño de los Órganos/efectos de los fármacos , Polvos , Esternón/efectos de los fármacos , Esternón/patologíaRESUMEN
Groups of 4 male Wistar rats were dosed intravenously with 14C-labeled benzo[a]pyrene dissolved in an Emulphor/water vehicle at 3 different dose levels and killed at 1 of 15 specific time intervals from 5 min to 32 h after dosing. 14C-Radiolabel concentration-time data were obtained for blood, brain, adipose, heart, kidney, liver, lung, spleen, and testes. Benzo[a]pyrene concentration-time data were obtained for blood, adipose, kidney, liver, and lung. Appropriate mathematical models were fitted to these data and to the data for metabolites derived as the residuals from 14C-radiolabel minus benzo[a]pyrene difference, where applicable. Nonlinear kinetics were found for 14C-radiolabel in liver, while the data from lung for both 14C-radiolabel and for benzo[a]pyrene per se supported the binding of benzo[a]pyrene in that tissue.
Asunto(s)
Benzo(a)pireno/farmacocinética , Carcinógenos Ambientales/farmacocinética , Tejido Adiposo/química , Tejido Adiposo/metabolismo , Animales , Área Bajo la Curva , Benzo(a)pireno/aislamiento & purificación , Carcinógenos Ambientales/aislamiento & purificación , Semivida , Inyecciones Intravenosas , Masculino , Modelos Biológicos , Ratas , Ratas Wistar , Distribución TisularRESUMEN
The subchronic toxicity of acridine was investigated in rats following dietary exposure at 0, 1, 10, 100 and 500 ppm for 13 weeks. The growth rate and food consumption were not affected by treatment and no clinical signs of toxicity were observed. There was a slight but significant decrease in spleen weight, both in absolute terms and as a percent of body weight, in the 500 ppm males and a slight increase in absolute thymus weight in the females of the same dose group. Both hepatic ethoxyresorufin O-deethylase (EROD) and pentoxyresorufin O-dealkylase (PROD) activities were slightly, but significantly, elevated in females in the 500 ppm dose group. No haematological or other biochemical changes were observed. Females also displayed dose-related increases in inorganic phosphate and uric acid levels. Treatment-related histopathological changes were seen in the thyroid, liver and kidney and included hepatic anisokaryosis and vesiculation of nuclei and glomerular adhesions, reticulin sclerosis and nuclear pyknosis in the kidney. Residue data showed a dose-dependent accumulation of acridine in liver, kidney and adipose with the highest concentration being found in the fat of the 500 ppm dose group. Based on these data, the no observable adverse effect level of acridine was judged to be 100 ppm or 12 mg/kg bw/day.
Asunto(s)
Acridinas/toxicidad , Acridinas/administración & dosificación , Animales , Peso Corporal/efectos de los fármacos , Calcio/sangre , Dieta , Relación Dosis-Respuesta a Droga , Femenino , Masculino , Microsomas Hepáticos/efectos de los fármacos , Microsomas Hepáticos/enzimología , Tamaño de los Órganos/efectos de los fármacos , Fosfatos/sangre , Ratas , Ratas Sprague-Dawley , Factores SexualesRESUMEN
The performance of polyethylene glycol-modified bovine hemoglobin (PEG-Hb) was evaluated in dogs following the replacement of 30% or 50% of their blood volume with PEG-Hb or lactated Ringer's solution (LRS). Dogs fully instrumented with catheters and blood pressure probes were transfused by simultaneous bleeding from the jugular vein and infusion of PEG-Hb or LRS via the cephalic vein. Animals were monitored for abnormal behavior and clinical signs for fourteen days. No mortalities, overt toxicity, changes in body weight, food consumption or ophthalmology, or discernable trends in hematology, blood chemistry coagulation, urinalysis or hemodynamic parameters that could be attributed to PEG-Hb were noted. Blood gas analyses were steady and within physiological ranges. Dose-related histopathological findings of vacuolated histiocytes in the femoral bone marrow, splenic parenchyma, the medulla of the mesenteric and mandibular lymph nodes, and vacuolated sinusoidal cells in the liver and the renal tubular epithelial cells were believed to be related to the phagocytosis and degradation of PEG-Hb by the reticulo-endothelial system. The maintenance of high oxygen levels in the circulation for the two-week treatment period, as well as the insignificant physiological and histopathological findings indicate that PEG-Hb could be a successful blood substitute.
Asunto(s)
Sustitutos Sanguíneos/toxicidad , Transfusión Sanguínea , Hemoglobinas/toxicidad , Polietilenglicoles/toxicidad , Animales , Aspartato Aminotransferasas/sangre , Conducta Animal/efectos de los fármacos , Bovinos , Perros , Recuento de Eritrocitos/efectos de los fármacos , Estudios de Evaluación como Asunto , Femenino , Hematócrito , Hemodinámica/efectos de los fármacos , Masculino , Oxígeno/sangre , Proyectos de Investigación , UrinálisisRESUMEN
The tissue distribution, metabolism, and excretion of 14C-labeled 2,4,4'-trichlorobiphenyl (CB-28) were studied in the rat. Following intravenous administration, radioactivity was removed from the blood rapidly and distributed to tissues. The time-courses of varying concentrations of CB-28 in tissues and blood were described mathematically using nonlinear regression analysis. The highest concentrations of radioactivity were found in the adipose and skin, which showed distinct uptake phases. High levels were seen at 30 minutes in liver and brain, but quickly declined. Fifty-two percent of the given dose was excreted in feces within 14 days. Intraperitoneal administration to three female rats for five consecutive days provided tissues which were analyzed for metabolites.
Asunto(s)
Bifenilos Policlorados/farmacocinética , Animales , Radioisótopos de Carbono , Femenino , Inyecciones Intraperitoneales , Inyecciones Intravenosas , Masculino , Bifenilos Policlorados/metabolismo , Bifenilos Policlorados/orina , Ratas , Ratas Sprague-Dawley , Distribución TisularRESUMEN
Deficiencies of antioxidants and increased free radical generation may explain the high incidence of bronchopulmonary dysplasia in premature infants. Long-acting antioxidants such as polyethylene glycol (PEG) conjugated superoxide dismutase (SOD), and catalase might modify this process. We delivered 32 premature lambs, 16 pairs of twins, by cesarean section at 125-141 days of gestation (term 146 days) and stabilized them on ventilators in normocapnic hyperoxia for a period of 8 h. One lamb of each twin pair received an intravenous dose of 7,500-50,000 IU/kg of PEG-SOD and of 37,500-1,000,000 IU/kg of PEG-catalase at birth. Their siblings acted as controls. Mean airway pressure, arterial pressure, and heart rate were recorded continuously. Arterial blood gases and pH were obtained every 30 min. After sacrifice, standardized lung biopsies were prepared for quantitative morphometrics and electron microscopy. Administration of PEG antioxidants at birth reduced the influx of neutrophils and macrophages into the lung and damage to arterioles, bronchiolar mucosa, and type II pneumocytes without major changes in alveolar surface area or pulmonary function. These effects were dose-related and detectable even at the lowest doses of PEG antioxidants administered.
Asunto(s)
Catalasa/farmacología , Pulmón/efectos de los fármacos , Oxígeno/envenenamiento , Polietilenglicoles/farmacología , Superóxido Dismutasa/farmacología , Animales , Animales Recién Nacidos/fisiología , Antioxidantes/farmacología , Edad Gestacional , Pulmón/patología , Pulmón/ultraestructura , Microvellosidades/ultraestructura , Oxígeno/antagonistas & inhibidores , OvinosRESUMEN
Six newborn infants affected by acute aseptic neonatal meningitis were attended during the months of June and July 1987. Fever, good general physical appearance and no associate focal symptomatology was the onset in five cases, whereas one of them had apnea spells. An increase in total cell count was present in CSF with polymorphonuclears predominance in two cases, being lymphocites more prevalent in the others. Enterovirus were demonstrated as a cause in three of them. After describing clinical facts and evolution, some epidemiological aspects are commented.
Asunto(s)
Infecciones por Enterovirus/epidemiología , Meningitis Viral/epidemiología , Brotes de Enfermedades , Humanos , Recién Nacido , Meningitis Viral/microbiología , España/epidemiologíaRESUMEN
Authors present four cases of neonatal necrotizing enterocolitis occurred during an outbreak of acute enteritis. From november 1985 to beginning of february 1986, forty-seven out of 588 newborn infants were involved. In 22 affected infants (46.8%) rotavirus were isolated from stools, whereas no bacterial or viral agent was recovered in 25 (53.2%). Four cases (8.6%) developed necrotizing enterocolitis.
Asunto(s)
Enterocolitis Seudomembranosa/epidemiología , Gastroenteritis/epidemiología , Infecciones por Rotavirus , Peso al Nacer , Infección Hospitalaria/epidemiología , Enterocolitis Seudomembranosa/etiología , Gastroenteritis/complicaciones , Gastroenteritis/etiología , Humanos , Recién NacidoRESUMEN
Modification by covalent attachment of monomethoxypolyethylene glycol (PEG) can reduce the immunogenicity and prolong the circulating life of injected enzymes, making their use as therapeutic agents feasible. We report the first clinical use of PEG-modified Arthrobacter protoformiae uricase (PEG-uricase) to treat hyperuricemia in a patient with non-Hodgkin lymphoma and renal insufficiency who was allergic to allopurinol. Two intramuscular injections totaling 3 U/kg body weight during the first 30 hours of treatment lowered the plasma urate level from 910 to 190 mumol/L (15.3 to 3.2 mg/dL), after which a dose of 2 U/kg every 5 to 6 days maintained the plasma urate level at 540 mumol/L (9 mg/dL) or lower. After the injection of PEG-uricase, uricase activity appeared in plasma rapidly, peaking within 24 hours and persisting for approximately 5 days; an inverse relation between plasma uricase activity and plasma urate concentration was noted. The agent was nontoxic and well tolerated. No antibody to either PEG-uricase or unmodified uricase developed over a 3-week period, during which four doses of PEG-uricase were administered. Because of its long circulating life, PEG-uricase is probably a more effective hypouricemic agent than unmodified uricase, which has previously had limited use. As an adjunct to cytolytic therapy for hematologic malignancies when protection from hyperuricemia is needed rapidly, PEG-uricase deserves further study.
Asunto(s)
Leucemia Linfocítica Crónica de Células B/sangre , Polietilenglicoles/uso terapéutico , Urato Oxidasa/uso terapéutico , Ácido Úrico/sangre , Esquema de Medicación , Humanos , Inyecciones Intramusculares , Enfermedades Renales/etiología , Leucemia Linfocítica Crónica de Células B/complicaciones , Masculino , Persona de Mediana Edad , Polietilenglicoles/administración & dosificación , Urato Oxidasa/administración & dosificación , Urato Oxidasa/sangreRESUMEN
The tissue distribution and excretion of three trichlorobenzene isomers (TCB) were investigated in the rat. Single doses of TCBs were administered orally to groups of 5 fasted rats at 10 mg/kg body weight. Serial sacrifices were carried out and the radioactivity contents were determined in tissues and blood. For all three TCB isomers, radioactivity appeared in the blood and tissues at 0.5 h, and peaked around 2-4 h after dosing. Fat, skin, and liver had high concentrations of the parent compound while kidney and muscle had high levels of metabolites. Elimination of TCB from tissues and blood can best be described by a two-compartmental open pharmacokinetic model. The terminal half-lives were 145, 93 and 68 h for 1,2,3-, 1,2,4 and 1,3,5-TCB isomer respectively. Ninety-five percent of the administered 1,2,3- and 89% of the 1,3,5-isomers were eliminated within 48 h in the urine and feces with the former being the major route.
Asunto(s)
Clorobencenos/farmacología , Animales , Radioisótopos de Carbono , Clorobencenos/orina , Heces/análisis , Isomerismo , Masculino , Ratas , Ratas Endogámicas , Relación Estructura-Actividad , Distribución TisularRESUMEN
Thirty-seven dogs with malignant lymphoma were treated with either polyethylene glycol conjugated (PEG) asparaginase alone (10-30 IU/kg intraperitoneally [IP] weekly--20 dogs) or PEG-asparaginase combined with one cycle of chemotherapy (vincristine, cyclophosphamide, methotrexate, and prednisone), followed by maintenance PEG-asparaginase (30 IU/kg, IP weekly--17 dogs). In the 20 dogs (eight were chemotherapy resistant) treated with PEG-asparaginase alone, seven had a complete response (CR), seven had a partial response (PR), five had no response (NR), and one was not evaluable (NE). The duration of response (CR + PR) ranged from 14 to 102 days (median, 48 days). In the eight chemotherapy-resistant dogs (seven were previously resistant to L-asparaginase) four had responses (one CR and three PR). In the 17 dogs treated with combined PEG-asparaginase and chemotherapy, 13 had a CR, two had a PR, and two had NR. None of the dogs had had prior chemotherapy, and the duration of response (CR + PR) ranged from 7 to 840+ days, with a median of 126+ days. Four dogs are still on maintenance PEG-asparaginase at 16+, 21+, 26+, and 28+ months. Toxicity consisted of death due to massive tumor breakdown (two dogs), disseminated intravascular coagulation (DIC--one dog), hypersensitivity reaction (one dog), vomiting (three dogs) and soft stools (three dogs). Four normal dogs were given very high doses of PEG-asparaginase (200 IU/kg and 1200 IU/kg) once weekly for two treatments without any significant toxicity. These results indicate that PEG-asparaginase has antitumor activity in dog with spontaneously occurring malignant lymphoma.
Asunto(s)
Asparaginasa/uso terapéutico , Enfermedades de los Perros/tratamiento farmacológico , Linfoma/tratamiento farmacológico , Animales , Asparaginasa/administración & dosificación , Asparaginasa/sangre , Asparaginasa/toxicidad , Perros , PolietilenglicolesRESUMEN
A conjugate of asparaginase and monomethoxypolyethylene glycol was evaluated in acute, subacute, and subchronic toxicologic studies in mice, rats, and dogs. The drug induced low-grade toxicosis. The appearance and behavior of rats and dogs were not affected by the treatment. Only large doses produced inactivity, loss of appetite, and loss of weight. The LD50 could not be established. The drug retarded slightly body weight gains in dogs and female rats and produced mild anemia in 30% of the female rats. Urinalysis and blood chemical determinations in rats and dogs were generally not affected by the treatment. Monomethoxypolyethylene glycol-asparaginase was detectable in the plasma of mice 13 days after IV, intraperitoneal, or IM administration, and in dogs for 3 to 4 weeks.
Asunto(s)
Asparaginasa/toxicidad , Polietilenglicoles/toxicidad , Animales , Asparaginasa/administración & dosificación , Perros , Femenino , Masculino , Ratones , Ratones Endogámicos C3H , Polietilenglicoles/administración & dosificación , Ratas , Ratas Endogámicas , Especificidad de la EspecieRESUMEN
The use of high oxygen concentrations and high mean airway pressures during mechanical ventilation of premature newborn infants with respiratory distress syndrome leads in 20%-30% of the survivors to chronic lung disease. This study explores if exogenous polyethylene glycol conjugated superoxide dismutase (PEG-SOD) and catalase (PEG-CAT) mitigate oxygen toxicity in premature lambs with respiratory distress syndrome. Six pairs of premature lambs were delivered by cesarean section and treated by tracheal instillation of 60 mg natural sheep surfactant/kg/body weight. After birth, all lambs were ventilated with 100% oxygen, and one of each pair received a single intravenous injection of 1 million U/kg PEG-CAT and 50,000 U/kg PEG-SOD. At 8 h of age or after respiratory failure was established, the lambs were killed and the lungs were removed intact. Lung damage was assessed by microscopy. The arterial blood gases, pH, and mean airway pressures of the lambs treated with PEG-SOD/PEG-CAT did not differ from those of the controls. Mean PaO2 was greater than 140 mmHg during the first 4 h of the experiments. In the lambs treated with PEG-SOD/PEG-CAT, SOD and CAT levels were very high during the study period and less bronchiolar epithelial damage and lung hemorrhages were found at microscopy.