RESUMO
BACKGROUND: The Sverdlovsk region of the Russian Federation is characterised by its abundance of natural resources and industries. Located in this region, Asbest city is situated next to one of the largest open-pit chrysotile asbestos mines currently operational; many city residents are employed in activities related to mining and processing of chrysotile. We compared mortality rates from 1997 to 2010 in Asbest city to the remaining Sverdlovsk region, with additional analyses conducted for site-specific cancer mortality. METHODS: Population and mortality data for Asbest city and Sverdlovsk region were used to estimate crude and age-specific rates by gender for the entire period and for each calendar year. Age-standardized mortality rates were also calculated for the adult population (20+) and Poisson regression was used to estimate standardized mortality ratios, overall and by gender. RESULTS: During the period of 1997 to 2010, there were similar mortality rates overall in Asbest and the Sverdlovsk region. However, there were higher rates of cancer mortality (18 % males; 21 % females) and digestive diseases (21 % males; 40 % females) in Asbest and lower rates of unknown/ill-defined in Asbest (60 % males; 47 % females). Circulatory disease mortality was slightly lower in Asbest. Cancer mortality was higher for men in Asbest from oesophageal, urinary tract and lung cancers compared to the Sverdlovsk region. In women, cancer mortality was higher for women in Asbest from stomach, colon, lung and breast cancers compared to the Sverdlovsk region. CONCLUSIONS: This large population-based analysis indicates interesting differences but studies with individual exposure information are needed to understand the underlying factors.
Assuntos
Asbestos Serpentinas , Mortalidade , Neoplasias/mortalidade , Adulto , Idoso , Cidades/epidemiologia , Exposição Ambiental/história , Feminino , História do Século XX , História do Século XXI , Humanos , Masculino , Pessoa de Meia-Idade , Mineração , Federação Russa/epidemiologia , Adulto JovemRESUMO
Studies of cancer risk following in utero exposure to ionizing radiation are limited in number, particularly for adult-onset cancers, and the evidence is unclear. In the present study, the risk of solid cancer incidence following in utero radiation exposure is examined among 8466 offspring of female nuclear workers at one of the largest nuclear facilities (Mayak Production Association) in the Russian Federation. Poisson regression methods were used to estimate excess relative risks (ERRs) per Gray (Gy). Mother's uterine gamma dose served as a surrogate for fetal gamma dose. During 277,002 person-years of follow-up (1948-2009), there were 177 first primary solid cancers excluding non-melanoma skin cancers. Estimated in utero gamma and plutonium doses exceeded zero for 41 and 23 % of offspring, respectively. Of the 177 solid cancers, 66 occurred among individuals with some in utero exposure to gamma radiation and 53 among those with estimated plutonium exposures. There was no indication of a statistically significantly increased risk of solid cancer incidence from in utero gamma exposure (linear ERR/Gy -1.0; upper 95 % confidence limit 0.5). This result was unchanged after accounting for subsequent occupational exposure. Plutonium doses were estimated but were too low to obtain meaningful risk estimates. Thus, in this cohort in utero radiation exposure was not associated with solid cancer risk. This is consistent with an earlier report of mortality in the cohort, but is based on twice as many cases and less susceptible to biases inherent in mortality analyses. Given the relatively young age of the cohort with respect to cancer, continued follow-up should be done as the number of cancer cases increases.
Assuntos
Troca Materno-Fetal , Neoplasias Induzidas por Radiação/epidemiologia , Exposição Ocupacional , Exposição à Radiação , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Raios gama , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Armas Nucleares , Gravidez , Risco , Federação Russa/epidemiologia , Adulto JovemRESUMO
BACKGROUND: Recent studies have suggested that several ovarian cancer risk factors differ by parity status, but these findings have not been confirmed. We evaluated whether known risk factors of ovarian cancer differ between nulliparous and parous women using data from two large prospective cohorts. METHODS: Data from the National Institutes of Health-AARP Diet and Health Study and the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial were combined for this analysis. Cox regression models were used to estimate associations with ovarian cancer risk. Risk heterogeneity by parity status was assessed using likelihood-ratio tests. RESULTS: Among the 125 437 women included in the analysis, there were 16 589 (13%) nulliparous women and 108 848 (87%) parous women. Of the 623 women diagnosed with invasive epithelial ovarian cancer, 102 (16%) were nulliparous and 521 (84%) were parous. While parity reduced ovarian cancer risk, no differences were found for other risk factors by parity. Among ever users of hormone therapy, body mass index suggestively increased the risk of ovarian cancer by 1.5-fold in nulliparous but not parous women (P-heterogeneity=0.08). CONCLUSION: While nulliparous women have higher ovarian cancer risk than parous women, our findings suggest that the relative effects of most other risk factors do not differ by parity.
Assuntos
Neoplasias Epiteliais e Glandulares/epidemiologia , Neoplasias Ovarianas/epidemiologia , Paridade , Idoso , Carcinoma Epitelial do Ovário , Estudos de Coortes , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos , Análise de Regressão , Fatores de Risco , Estados Unidos/epidemiologiaRESUMO
BACKGROUND: Little is known about leukaemia risk following chronic radiation exposures at low dose rates. The Techa River Cohort of individuals residing in riverside villages between 1950 and 1961 when releases from the Mayak plutonium production complex contaminated the river allows quantification of leukaemia risks associated with chronic low-dose-rate internal and external exposures. METHODS: Excess relative risk models described the dose-response relationship between radiation dose on the basis of updated dose estimates and the incidence of haematological malignancies ascertained between 1953 and 2007 among 28 223 cohort members, adjusted for attained age, sex, and other factors. RESULTS: Almost half of the 72 leukaemia cases (excluding chronic lymphocytic leukaemia (CLL)) were estimated to be associated with radiation exposure. These data are consistent with a linear dose response with no evidence of modification. The excess relative risk estimate was 0.22 per 100 mGy. There was no evidence of significant dose effect for CLL or other haematopoietic malignancies. CONCLUSION: These analyses demonstrate that radiation exposures, similar to those received by populations exposed as a consequence of nuclear accidents, are associated with long-term dose-related increases in leukaemia risks. Using updated dose estimates, the leukaemia risk per unit dose is about half of that based on previous dosimetry.
Assuntos
Leucemia Induzida por Radiação/epidemiologia , Rios , Estudos de Coortes , Exposição Ambiental/estatística & dados numéricos , Feminino , Seguimentos , Humanos , Incidência , Masculino , Neoplasias Induzidas por Radiação/epidemiologia , Liberação Nociva de Radioativos , Características de Residência/estatística & dados numéricos , Federação Russa/epidemiologia , Fatores de TempoRESUMO
The transversus abdominis plane (TAP) block is a well known method for postoperative pain control after abdominal surgery. From an anatomical and physiological point of view it should be possible to perform abdominal wall surgery, e.g. wound debridement, using a TAP block only. To the authors knowledge no studies have been published with respect to the use of TAP only. This article presents a case report demonstrating that it is possible to perform three consecutive operation procedures within 7 days using only a bilateral TAP catheter technique. The TAP block without any co-medication provides high patient comfort and should be recognized as a good alternative for abdominal wall surgery.
Assuntos
Parede Abdominal/cirurgia , Anestesia/métodos , Bloqueio Nervoso/métodos , Músculos Abdominais , Parede Abdominal/diagnóstico por imagem , Anestésicos Intravenosos , Desbridamento , Feminino , Humanos , Laparoscopia , Midazolam , Pessoa de Meia-Idade , Ultrassonografia de IntervençãoRESUMO
International studies suggest a growing risk of posttraumatic stress disorder (PTSD) with an increasing duration of deployment. There are no data available for the German armed forces that would allow an assessment of the average mission duration of about 4 months. Analyses are based on a stratified random sample of 1,483 ISAF soldiers. Standardized diagnostic interviews were conducted about 12 months after soldiers returned from mission. Deployment duration was categorized into 1-2 months, 3-5 months, and 5-8 months. Additionally, dimensional analyses of deployment duration were performed. Deployment duration was associated with the number of stressful and traumatic events. Notwithstanding, we found no linear relationship between mission duration and PTSD risk, neither in the total sample nor in the defined subgroups. However, we found a bimodal distribution suggesting an increased PTSD risk in the first 2 months and - less pronounced and limited to the Kunduz location - for deployment durations of at least 6 months. There was no general increase in PTSD risk with increasing deployment durations for German soldiers in this naturalistic study. The higher risk for soldiers with short deployments might be explained by selection of vulnerable subjects and different deployment characteristics. Further, there is some evidence of an increased PTSD risk for soldiers deployed for longer periods to high-risk locations (e.g., Kunduz).
Assuntos
Campanha Afegã de 2001- , Distúrbios de Guerra/epidemiologia , Guerra do Iraque 2003-2011 , Militares/estatística & dados numéricos , Transtornos de Estresse Pós-Traumáticos/epidemiologia , Carga de Trabalho/estatística & dados numéricos , Adulto , Feminino , Alemanha/epidemiologia , Humanos , Acontecimentos que Mudam a Vida , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Inquéritos e Questionários , Adulto JovemRESUMO
We have previously demonstrated that the chemopreventive agent dehydroepiandrosterone (DHEA) inhibits the isoprenylation of cellular proteins by depletion of endogenous mevalonate. We now report that treatment of HT-29 SF human colonic adenocarcinoma cells with DHEA at concentrations ranging from 12.5 to 200 microM for up to 72 h inhibited growth and arrested cells in the G1 phase of the cell cycle in a time- and dose-dependent manner. Exposure to 25 or 50 microM DHEA also transiently delayed cells in G2M phase after 48 h. Addition of mevalonic acid partially overcame both the growth and cell cycle effects of 25 microM DHEA in the initial 48 h. During prolonged exposure (72 h), the addition of mevalonic acid as well as cholesterol was required to reconstitute cell cycle progression. This suggests that the depletion of endogenous mevalonate and other isoprenoids is involved in DHEA-mediated growth inhibition and cell cycle arrest.
Assuntos
Adenocarcinoma/patologia , Ciclo Celular/efeitos dos fármacos , Neoplasias do Colo/patologia , Desidroepiandrosterona/farmacologia , Adenocarcinoma/metabolismo , Colesterol/farmacologia , Neoplasias do Colo/metabolismo , Desidroepiandrosterona/antagonistas & inibidores , Desoxirribonucleosídeos/farmacologia , Humanos , Ácido Mevalônico/farmacologia , Ribonucleosídeos/farmacologia , Esqualeno/farmacologia , Fatores de Tempo , Células Tumorais CultivadasRESUMO
BACKGROUND AND OBJECTIVE: Weakening of the lateral rectus muscle to correct exotropia can be achieved by using a conventional or a hang-back recession. This study was conducted to compare the results of these techniques and to analyze the dose-response curve and complication rates. STUDY DESIGN AND METHODS: Patients who underwent a lateral rectus muscle recession for exotropia were included in this retrospective study. The recession was performed conventionally with direct scleral fixation at the desired point or with a hang-back recession, each combined with a plication of the ipsilateral medial rectus muscle. The study analyzed ocular alignment and motility preoperatively as well as 1 day and 3 months postoperatively. Intraoperative and postoperative complications were compared. RESULTS: A total of 50 patients (age 4-75 years) met the inclusion criteria for this study. A conventional recession of the lateral rectus muscle was performed in 30 patients and a hang-back recession in 20. Preoperative ocular alignment with distance fixation was - 33.8 ± 14.4 prism diopters (PD) in the conventional group and - 30.6 ± 11.8 PD (mean ± standard deviation) in the hang-back group (where negative values constitute exotropia and positive values are esotropia). Preoperative ocular alignment with near fixation was - 40 ± 15.2 PD and - 36 ± 14.7 PD for conventional and hang-back recession, respectively. Ocular alignment with distance fixation 3 months postoperatively was - 10 ± 14.1 PD in the conventional group and - 11.1 ± 13.2 PD in the hang-back group and with near fixation it was - 15.4 ± 13.9 PD and - 11.5 ± 13.9 PD, respectively. In the conventional group 1 mm of combined surgery corrected 2.03 ± 0.88 PD (- 0.31-4.15 PD/mm) of exotropia with distance fixation and 2.13 ± 0.87 PD (0.89-3.85 PD/mm) with near fixation. In the hang-back group, it corrected 1.83 ± 0.89 PD (0.42-2.95 PD/mm) and 2.32 ± 1.25 PD (0.17-4.76 PD/mm), respectively. Differences between groups were not statistically significant. Intraoperative complications, such as scleral perforation were not observed. Postoperative complications, particularly slipped or lost muscles or induced vertical strabismus were not documented in either group. CONCLUSION: The hang-back recession is an effective and safe alternative to conventional recession of the lateral rectus muscle for exotropia. Larger studies with longer follow-up would be desirable to prospectively compare these two techniques.
Assuntos
Exotropia/diagnóstico , Exotropia/cirurgia , Músculos Oculomotores/cirurgia , Procedimentos Cirúrgicos Oftalmológicos/métodos , Procedimentos de Cirurgia Plástica/métodos , Transtornos da Visão/prevenção & controle , Adolescente , Adulto , Idoso , Criança , Exotropia/complicações , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Transtornos da Visão/diagnóstico , Transtornos da Visão/etiologia , Acuidade Visual , Adulto JovemRESUMO
Long-term effects of in utero exposure to ionizing radiation remain poorly quantified in humans. In this study, the risk of hematologic malignancies was investigated in offspring of female workers of the Mayak Production Association, a large Russian nuclear facility. Excess relative risks (ERR) for exposure to gamma radiation and plutonium were estimated in a cohort of 8,466 offspring who were born between January 1, 1948 and December 31, 1988 and followed until 2009. An unstable linear ERR of 1.12 (95% CI 0.11-3.44) per 100 mGy gamma exposure in utero was estimated based on 32 incident hematologic malignancies in 277,002 person-years under risk. The ERR was increased in the dose category 20-79 mGy gamma exposure in utero (1.75, 95% CI 0.04; 5.63), while the other dose categories showed decreased or unstable estimates. Leukemia showed an ERR of 1.76 (95% CI 0.01-8.33) per 100 mGy based on 13 cases. There was no consistent association with plutonium exposure. While an increased risk of hematologic malignancies after gamma exposure in utero was suggested, the small numbers prevented more definitive conclusions.
Assuntos
Neoplasias Hematológicas/epidemiologia , Neoplasias Induzidas por Radiação/epidemiologia , Exposição Ocupacional/efeitos adversos , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Adolescente , Adulto , Criança , Pré-Escolar , Estudos de Coortes , Relação Dose-Resposta à Radiação , Feminino , Humanos , Lactente , Recém-Nascido , Pessoa de Meia-Idade , Gravidez , Risco , Federação Russa/epidemiologia , Adulto JovemRESUMO
The association between hyperthyroidism and thrombocytopenia is a known although infrequent clinical condition. Distinct mechanisms are probably active in each particular case, but the thyrotoxic state has been implicated as having a key effect on the fall in the number of platelets. We describe a patient with coexisting Graves' disease and idiopathic thrombocytopenic purpura who showed special refractoriness to treatment of the bleeding condition in the thyrotoxic state, but who promptly responded to treatment when the thrombocytopenia relapsed 2 1/2 years later, while he was euthyroid. Thus, in this case, a clear exacerbating effect of the thyrotoxic state on the thrombocytopenia was observed. We suggest evaluation of the thyroid condition in patients suffering from refractory thrombocytopenia.
Assuntos
Doença de Graves/complicações , Púrpura Trombocitopênica/etiologia , Adulto , Antitireóideos/uso terapêutico , Feminino , Doença de Graves/tratamento farmacológico , Humanos , Púrpura Trombocitopênica/tratamento farmacológico , Remissão EspontâneaRESUMO
Two patients with adult respiratory distress syndrome (ARDS) caused by Legionnaires' disease were treated with erythromycin lactobionate, and they survived. Sequential pulmonary function studies and chest roentgenograms were obtained in both patients. Despite previous suggestions that severe fibrosis might complicate the recovery of patients with this disease, both patients had normal lung volumes and only minimal reduction in single-breath carbon monoxide diffusing capacity ten weeks after the onset of the disease. Thus, pulmonary function after ARDS caused by Legionnaires' disease seems to be only minimally disturbed.
Assuntos
Doença dos Legionários/complicações , Pulmão/fisiopatologia , Síndrome do Desconforto Respiratório/etiologia , Adulto , Eritromicina/análogos & derivados , Eritromicina/uso terapêutico , Humanos , Doença dos Legionários/tratamento farmacológico , Medidas de Volume Pulmonar , Masculino , Pessoa de Meia-Idade , Capacidade de Difusão Pulmonar , Síndrome do Desconforto Respiratório/fisiopatologia , EspirometriaRESUMO
BACKGROUND: Magnesium sulfate has been helpful in the treatment of acute exacerbations of asthma. We hypothesized that magnesium would also be an effective bronchodilator in patients with chronic stable asthma. METHODS: We performed a prospective, randomized, double-blind, placebo-controlled, crossover trial in 15 patients with chronic, stable asthma and 10 nonasthmatics. On study day 1, spirometry and albuterol challenge were used to confirm the presence of asthma according to American Thoracic Society criteria. On study day 2, subjects received intravenous magnesium sulfate (2 g) or placebo (saline). On study day 3, subjects were crossed over to receive the other drug. Spirometry was performed before, during, and after drug or placebo administration. Circulating ionized magnesium concentrations were determined before and after intravenous magnesium or placebo administration. RESULTS: Magnesium infusion caused no statistically significant changes in forced expiratory volume in 1 second (mean +/- SEM, 1.92 +/- 0.13 L before, 1.98 +/- 0.12 L during, and 2.01 +/- 0.14 L after magnesium administration), forced vital capacity (mean +/- SEM, 3.44 +/- 0.25 L before, 3.60 +/- 0.26 L during, and 3.59 +/- 0.25 L after magnesium administration), or maximum forced expiratory flow rate (mean +/- SEM, 5.42 +/- 0.44 L/second before, 5.46 +/- 0.46 L/second during, and 5.57 +/- 0.49 L/second after magnesium administration). Placebo caused no changes in these three physiologic variables. CONCLUSION: Magnesium is not effective as a bronchodilator in chronic, stable asthmatics or in normal non-asthmatic adults.
Assuntos
Asma/tratamento farmacológico , Sulfato de Magnésio/uso terapêutico , Adulto , Asma/sangue , Asma/fisiopatologia , Doença Crônica , Método Duplo-Cego , Feminino , Humanos , Masculino , Estudos Prospectivos , Testes de Função Respiratória , Falha de TratamentoRESUMO
This paper aimed to extend the existing knowledge on the association between PTSD symptoms, alcohol use disorders (AUD) and nicotine dependence (ND) by distinguishing between anxious and dysphoric arousal PTSD symptoms and by considering the putative contribution of additional comorbidity. Data stem from a cross-sectional study in a stratified, representative sample of 1483 recently deployed soldiers using standardized diagnostic interviews. All lifetime PTSD symptom clusters (occurrence of any symptom and number of symptoms) were associated with current AUD and ND in crude models except that anxious arousal was not related to AUD. Associations were reduced in magnitude when controlling for comorbidity. Current ND was related to the occurrence of any emotional numbing and to the number of re-experiencing symptoms above the contribution of other symptom clusters and comorbidity. In conclusion, associations between PTSD symptoms, AUD and ND may be partially attributable to additional comorbidity. Findings also yield further evidence for a role of emotional numbing and re-experiencing symptoms in the comorbidity between PTSD and ND and for a distinction between dysphoric and anxious arousal PTSD symptoms.
Assuntos
Militares/psicologia , Transtornos de Estresse Pós-Traumáticos/psicologia , Transtornos Relacionados ao Uso de Substâncias/psicologia , Adulto , Nível de Alerta/fisiologia , Estudos Transversais , Diagnóstico Duplo (Psiquiatria) , Emoções , Feminino , Humanos , MasculinoRESUMO
BACKGROUND: Several studies have documented factors related to increase in alcohol consumption in the context of stressful experiences. However, little is known about predictors of different courses of alcohol use in this context. This study aims to investigate diverse predictors and correlates of increase and decrease of average daily alcohol consumption (aDAC) in the aftermath of military deployment taking into account a variety of potentially relevant factors. METHODS: N=358 soldiers were examined before (T1) and 12 months after return from deployment (T2) using standardized interviews. Change in aDAC was categorized into decreased (n=72), stable (n=215) and increased (n=71) aDAC. RESULTS: Overall, aDAC did not change significantly between T1 and T2 (median change=0.0 g, inter quartile range=11.3g). Compared to stable aDAC, increase was characterized by a lower proportion of high-educated individuals (OR: 0.3 (0.1-0.7), p=0.008), lower rank (marginally significant: OR: 2.0 (1.0-4.1), p=0.050), and less acceptance (trend: MR: 0.97 (0.93-1.00), p=0.053). Correlates of increased aDAC were less social support (MR: 0.84 (0.71-0.99), p=0.043), more sleeping problems (MR: 1.15 (1.00-1.31), p=0.045) and more negative post-event cognitions following deployment (MR: 2.32 (1.28-4.21), p=0.006). Decrease in aDAC was predicted by lower PTSD symptom severity before deployment (MR: 0.34 (0.16-0.72), p=0.005) and less childhood emotional neglect (marginally significant: MR: 0.78 (0.60-1.00), p=0.050). CONCLUSIONS: Increase and decrease in alcohol use after stressful experiences might have differential risk factors and correlates. Findings might stimulate future research that could result in improved measures to prevent increases as well as in interventions that could foster decreases in alcohol consumption in the context of stressful experiences.
Assuntos
Consumo de Bebidas Alcoólicas/epidemiologia , Militares/estatística & dados numéricos , Adulto , Consumo de Bebidas Alcoólicas/psicologia , Feminino , Seguimentos , Alemanha/epidemiologia , Humanos , Masculino , Saúde Mental , Fatores de Risco , Fatores Socioeconômicos , Transtornos de Estresse Pós-Traumáticos/epidemiologia , Transtornos de Estresse Pós-Traumáticos/psicologia , Adulto JovemRESUMO
Six patients with refractory neurosarcoidosis were enrolled in a 12-month open-label trial to investigate the safety and efficacy of cyclosporine therapy. Patients were stabilized on a corticosteroid dose, randomized to a low-dose or high-dose cyclosporine group (with appropriate target whole blood cyclosporine levels) for 6 months, and assessed by prospectively defined studies. The corticosteroid dose was adjusted as clinically tolerated. We found that the corticosteroid dose could be lowered to 30% to 58% of the initial stabilization dose in conjunction with cyclosporine therapy, at the time of maximal clinical and laboratory improvement. However, four patients deteriorated while using corticosteroids and cyclosporine; one of these patients died. At the time of clinical deterioration, the prednisone dose ranged from 6 to 22.5 mg daily (or the equivalent). No serious toxic effects developed from cyclosporine therapy. Cyclosporine treatment is a reasonably safe and effective adjunct to corticosteroid therapy for patients with refractory neurosarcoidosis, although clinical deterioration can occur despite combination therapy.
Assuntos
Ciclosporina/uso terapêutico , Doenças do Sistema Nervoso/tratamento farmacológico , Sarcoidose/tratamento farmacológico , Adulto , Glicemia/análise , Proteínas do Líquido Cefalorraquidiano/análise , Contagem de Eritrócitos , Potenciais Evocados , Feminino , Humanos , Imunoglobulina G/líquido cefalorraquidiano , Masculino , Pessoa de Meia-Idade , Doenças do Sistema Nervoso/sangue , Doenças do Sistema Nervoso/fisiopatologia , Peptidil Dipeptidase A/sangue , Prednisona/uso terapêutico , Sarcoidose/sangue , Sarcoidose/fisiopatologia , Nervo Tibial/fisiopatologiaRESUMO
PURPOSE: Amiodarone has proven to be effective in many cases of cardiac arrhythmias, refractory ventricular tachycardia, and ventricular fibrillation. Pulmonary toxicity is a possible side effect of the drug, with a reported incidence of 2 to 15 percent per year. To determine the effect of amiodarone on lung function, we prospectively studied serial lung function tests in a cohort of 91 patients with refractory cardiac arrhythmias treated with this agent. PATIENTS AND METHODS: Spirometry and carbon monoxide diffusing capacity (DLCO) were measured at zero, three, six, 12, 18, and 24 months, with a mean follow-up of 351 days. RESULTS: For the whole population taking a mean dose of amiodarone of 367 mg daily (range: 136 to 512 mg), there was no accelerated rate of decline in spirometric indices or DLCO. Analysis of lung function changes by multivariate analysis demonstrated that an accelerated decline in DLCO values occurred in elderly patients (p less than 0.05) but not in patients with pre-existing lung disease or cigarette smokers. In four patients (4.5 percent), clinical evidence of amiodarone pulmonary toxicity developed that was associated with a fall in DLCO of greater than 20 percent. All four patients recovered after the drug was stopped. Another 15 patients, without clinical evidence of pulmonary toxicity, had a sustained decline in DLCO of greater than 20 percent. These 15 patients remained asymptomatic over the next 11 months without interruption of therapy. A greater than 20 percent fall in DLCO was a sensitive test for clinically evident amiodarone pulmonary toxicity, but had a positive predictive value of only 21 percent. CONCLUSION: An isolated fall in DLCO, in the absence of clinical evidence of toxicity, does not necessitate stopping amiodarone. An unchanged DLCO value appears to be a reliable negative predictor of pulmonary toxicity.
Assuntos
Amiodarona/efeitos adversos , Pulmão/efeitos dos fármacos , Adulto , Idoso , Idoso de 80 Anos ou mais , Monóxido de Carbono/metabolismo , Difusão , Feminino , Seguimentos , Volume Expiratório Forçado , Humanos , Pulmão/metabolismo , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Espirometria , Capacidade VitalRESUMO
BACKGROUND: ATP resynthesis during reperfusion after liver preservation has been shown to be well correlated with the function of transplanted grafts. Nevertheless, the advantages of a cellular energy charge loading during the preservation period are yet not fully understood. This study evaluates the effects of different nucleotide levels at the end of preservation on metabolic changes and oxidative stress during reperfusion. METHODS: Two experimental groups were chosen reflecting different energy charge states after preservation: static cold storage for 10 hr and hypothermic oxygenated oscillating perfusion for 10 hr. In both experimental groups, normothermic ex vivo acellular reperfusion over 40 min was performed. A third group consisted of nonpreserved livers similarly reperfused for 40 min. Superoxide formation was detected by the superoxide dismutase inhibitable reduction of ferricytochrome c added to the normothermic perfusate. RESULTS: Superoxide formation and lipid peroxidation malondialdehyde were significantly lower during reperfusion after the energy charge loading before reperfusion by the hypothermic oscillating perfusion technique. However, oxygen radical formation, liver cell injury (lactate dehydrogenase [LDH] release), and TNFalpha release were significantly higher in energy charge-depleted groups (nonpreserved and cold stored livers). CONCLUSIONS: Hypothermic oscillating oxygenated perfusion led to the elevated energy charge during preservation and led to reduced oxygen radical formation as well as less lipid peroxidation during reperfusion, in contrast to cold stored livers and nonpreserved livers. This suggests a correlation between the energy charge before reperfusion and oxygen radical formation as well as liver injury at reperfusion.
Assuntos
Fígado , Preservação de Órgãos , Estresse Oxidativo , Animais , Biomarcadores/análise , Criopreservação , Hipotermia , Peroxidação de Lipídeos/fisiologia , Glicogênio Hepático/análise , Masculino , Malondialdeído/análise , Perfusão , Ratos , Ratos Endogâmicos BN , Reperfusão , Superóxidos/metabolismo , Fator de Necrose Tumoral alfa/análiseRESUMO
Exposure of human and animal cells to inhibitors of topoisomerase I or II has recently been shown to alter gene expression and induce differentiation in a number of experimental systems. We have previously shown that nalidixic acid and novobiocin, inhibitors of topoisomerase II, induce DNA hypomethylation. Since DNA hypomethylation is frequently associated with transcriptional activation, we wished to further explore the relationship between inhibition of DNA topoisomerases and enzymatic DNA methylation. When HT-29 human colonic adenocarcinoma cells were exposed to the specific topoisomerase II inhibitor teniposide (VM-26), a dose-dependent hypomethylation of DNA was observed during the window of drug treatment. Exposure to the topoisomerase I inhibitor camptothecin (CPT) produced a small but not statistically significant trend toward DNA hypomethylation. CPT-treated cells were found to have up to 19 fold increased levels of topoisomerase II protein, which may have compensated for decreased levels of non-drug-bound topoisomerase I. Both VM-26 and CPT were found to increase [H-3]thymidine incorporation into DNA when administered in low dose (0.5 muM VM-26; 8 nM CPT). Combination of VM-26 and CPT (0.5 muM and 8 nM, respectively) produced DNA hypomethyltion, a synergistic increase in [H-3]thymidine incorporation, and an increasing number of cells entering a higher DNA ploidy cycle. Since VM-26 interferes with the DNA strand breakage-reunion reaction by stabilizing a topoisomerase II-relaxed DNA complex, our results suggest that DNA existing in this form may be a poor substrate for DNA methylase. Topoisomerase inhibitor-induced DNA hypomethylation may offer a possible explanation for the induction of differentiation observed upon exposure to this family of drugs. Altered topoisomerase activity occurring during the process of tumor progression may also provide a link between the induction of polyploidy, DNA hypomethylation and aberrant gene expression frequently observed in tumor cells.
RESUMO
Topical cardiac hypothermia has been shown to be a safe and effective means of providing protection for the ischemic myocardium during aortic cross-clamping. We report herein two cases of postoperative bilateral diaphragmatic paralysis which we believe resulted from hypothermic injury to the phrenic nerves. After open-heart surgery, both patients experienced prolonged weaning from assisted ventilation and severe orthopnea. Return of normal diaphragmatic and phrenic nerve function was demonstrated in one patient ten months after surgery. Failure to correctly interpret the respiratory failure and orthopnea led to confusion and erroneous types of therapy. Awareness of this complication should lead to improved care and postoperative management of patients.
Assuntos
Parada Cardíaca Induzida/efeitos adversos , Nervo Frênico/lesões , Paralisia Respiratória/etiologia , Adulto , Ponte de Artéria Coronária , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologiaRESUMO
Legionella pneumophila has, in recent years, emerged as a common pulmonary pathogen in the normal and immuno-compromised patient (ICP). Making a specific etiologic diagnosis of pneumonia in the latter group is a common clinical dilemma often complicated by poor specimen availability and risks of invasive procedures. Improved staining and isolation techniques for L pneumophila would suggest that early diagnosis could be possible if adequate specimens were available. This report summarizes our experience with bronchoalveolar lavage (BAL) with which we have diagnosed L pneumophila in eight immunocompromised patients, well in advance of more traditional methods. On the basis of this experience, we would advocate early BAL in the ICP as a rapid, safe, moderately sensitive and specific diagnostic test to aid in the identification of L pneumophila.