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INTRODUCTION: The optimum follow-up regimen after treatment for early-stage endometrial cancer with curative intent is unknown. The National Comprehensive Cancer Network recommends a physical exam and vaginal cytology every three to six months for two years then at six to 12 month intervals with annual chest X-rays (CXR). However, there is debate as to whether intensive follow-up results in an improvement in outcomes for those with recurrent endometrial cancer. OBJECTIVE: To determine if intensive surveillance for recurrent cancer in women with early-stage endometrial cancer improves their outcomes. MATERIALS AND METHODS: The Roswell Park Cancer Institute tumor registry was used to identify patients with Stage I and II endometrial cancer initially diagnosed and treated over an 18-year period, who subsequently recurred. Clinico-pathological variables were abstracted. Patients were divided into two groups, depending on their mode of diagnosis of recurrent cancer: 1) routine screening, or 2) symptomatic. The outcomes between the two groups were compared. RESULTS: Fifty-two patients met inclusion criteria. Twenty-three patients were diagnosed via routine screening methods and 29 were symptomatic at presentation. Groups were equally represented with respect to age, stage, grade, adjuvant therapy, site of recurrence (local, distant), and time to recurrence (p > 0.05). Median survival time was 79 months for those diagnosed during routine screening and 80 months for symptomatic patients (p > 0.05). CONCLUSION: Pap smear and CXR appear to be of limited utility as the present study has shown that women diagnosed as a result of intensive surveillance did not have a better outcome than those who presented when symptomatic.
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Detecção Precoce de Câncer , Neoplasias do Endométrio/patologia , Recidiva Local de Neoplasia/diagnóstico , Vigilância da População , Idoso , Doenças Assintomáticas , Intervalo Livre de Doença , Neoplasias do Endométrio/diagnóstico , Neoplasias do Endométrio/cirurgia , Feminino , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Radiografia Torácica , Fatores de Tempo , Esfregaço VaginalRESUMO
BACKGROUND: Small numbers of tests with pending results are documented in hospital discharge summaries leading to breakdown in communication and medical errors due to inadequate followup. OBJECTIVE: Evaluate effect of using a computerized provider order entry (CPOE) system to enforce documentation of tests with pending results into hospital discharge summaries. METHODS: We assessed the percent of all tests with pending results and those with actionable results that were documented before (n = 182 discharges) and after (n = 203 discharges) implementing the CPOE-enforcement tool. We also surveyed providers (n = 52) about the enforcement functionality. RESULTS: Documentation of all tests with pending results improved from 12% (87/701 tests) before to 22% (178/812 tests) (p = 0.02) after implementation. Documentation of tests with eventual actionable results increased from 0% (0/24) to 50% (14/28)(p<0.001). Survey respondents felt the intervention improved quality of summaries, provider communication, and was not time-consuming. CONCLUSIONS: A CPOE tool enforcing documentation of tests with pending results into discharge summaries significantly increased documentation rates, especially of actionable tests. However, gaps in documentation still exist.
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AIMS: To explore and to compare the outcome of patients diagnosed with stage II/III/IV and stage III/IV endometrioid adenocarcinoma (EAC) with their serous carcinoma (USC) counterparts. MATERIALS AND METHODS: A total of 107 patients (73 EAC and 34 USC) were evaluated. For statistical analysis, the following baseline variables were considered for their prognostic value: the patient's age at presentation, the tumor size, the depth of myometrial invasion (MI), the lympho-vascular involvement (LVI) and the USC and the EAC subtypes (considered as binary variables). Disease free survival (DFS), death of disease (DOD) and overall survival (OS) were assessed using univariate and multiple Cox proportional hazards models. RESULTS: In univariate analysis, USC tends to recur more frequently than EAC (p = 0.004), a finding that disappeared in multivariate analysis. Furthermore, tumor histology had no significance in predicting the tumor outcomes. Among all of the prognostic factors and after adjusting for the aforementioned variables, MI ≥50% was the only independent factor in predicting DOD in stages II/III/IV (p = 0.009) and in stages III/IV (p = 0.004). MI was also an independent predictive factor for OS (p = 0.02) and early recurrences in stages III/IV. LVI was the only independent factor in predicting recurrences (p = 0.004) in stages II/III/IV but not in stages III/IV. CONCLUSION: Based on our study, tumor histology was not a significant factor in predicting disease outcome in stages II/III/IV and II/IV. Despite our limited sample size, we believe that our findings provide meaningful insights into the clinical study of endometrial cancer patients which in turn warrants further investigation.
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Carcinoma Endometrioide/secundário , Cistadenocarcinoma Seroso/secundário , Neoplasias do Endométrio/patologia , Valor Preditivo dos Testes , Adulto , Idoso , Carcinoma Endometrioide/mortalidade , Cistadenocarcinoma Seroso/mortalidade , Intervalo Livre de Doença , Neoplasias do Endométrio/mortalidade , Europa (Continente) , Feminino , Humanos , Metástase Linfática , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , Projetos de Pesquisa , Medição de Risco , Fatores de Risco , Estados UnidosRESUMO
Pegylated liposomal doxorubicin (PLD) is an effective and tolerable agent in the treatment of recurrent and refractory ovarian carcinoma. One of the most common dose-limiting toxicities of PLD is palmar-plantar erythrodysesthesia (PPE). We report a retrospective review of patients who took cod liver oil (CLO) while being treated with PLD at Roswell Park Cancer Institute. None of the patients required dose reduction, treatment interruption or discontinuation secondary to skin toxicity. No patient experienced grade 2 or greater PPE. The mechanism for the development of PLD-induced PPE is unknown. CLO may possibly mitigate it via decreased extravasation of PLD and/or by a blunting of the local inflammatory response. The effects of CLO should be further evaluated in a prospective, randomized trial, and attempts to elucidate the mechanism by which CLO may exert its effects should be pursued.
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Antibióticos Antineoplásicos/efeitos adversos , Óleo de Fígado de Bacalhau/administração & dosagem , Doxorrubicina/análogos & derivados , Toxidermias/prevenção & controle , Eritema/prevenção & controle , Dermatoses do Pé/prevenção & controle , Dermatoses da Mão/prevenção & controle , Neoplasias Ovarianas/tratamento farmacológico , Polietilenoglicóis/efeitos adversos , Administração Oral , Antibióticos Antineoplásicos/uso terapêutico , Doxorrubicina/efeitos adversos , Doxorrubicina/uso terapêutico , Toxidermias/etiologia , Eritema/induzido quimicamente , Feminino , Dermatoses do Pé/induzido quimicamente , Dermatoses da Mão/induzido quimicamente , Humanos , Parestesia/induzido quimicamente , Parestesia/prevenção & controle , Polietilenoglicóis/uso terapêuticoRESUMO
PURPOSE: Role of microRNAs in malignancies is well established due their regulatory role in cellular differentiation, proliferation and cell cycle control. Our purpose was to determine miRNA profiles of serially established ovarian cancer cell lines and the effect of genistein treatment. METHODS: Cell lines (UL-3A, UL-3B) were established from one patient during progression of disease. miRNA profiling was performed in untreated and genistein-treated cells. Estrogen receptors (ER) were studied with real-time polymerase chain reaction (RT-PCR) and Western immunoblotting. In vitro migration and invasion assays were utilized. RESULTS: While 108 miRNAs were expressed equally in both cell lines and their genistein-treated counterparts, an additional 53 miRNAs were differentially expressed. Genistein resulted in induction of ERalpha and ERbeta in ovarian cancer cells. A significant reduction in migration and invasion of UL-3A and UL-3B was demonstrated in genistein-treated cells. CONCLUSION: Common and unique miRNA profiles were demonstrated between the two cell lines, some of which were altered by genistein.
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Genisteína/farmacologia , MicroRNAs/efeitos dos fármacos , Neoplasias Ovarianas/tratamento farmacológico , Inibidores de Proteínas Quinases/farmacologia , Linhagem Celular Tumoral , Receptor alfa de Estrogênio/metabolismo , Receptor beta de Estrogênio/metabolismo , Feminino , HumanosRESUMO
BACKGROUND: Crohn's disease is a chronic inflammatory disorder of the gastrointestinal tract. Because Crohn's disease is transmural it may form fistulas to adjacent structures, including the perineum and vulva. CASE: A 28-year-old white female with a history of Crohn's disease presented with a non-healing vulvar fistula. Biopsy revealed squamous cell carcinoma. CONCLUSION: Young women may develop squamous cell carcinoma associated with fistulae of Crohn's disease.
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Carcinoma de Células Escamosas/complicações , Doença de Crohn/complicações , Neoplasias Vulvares/complicações , Adulto , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/cirurgia , Feminino , Humanos , Biópsia de Linfonodo Sentinela , Neoplasias Vulvares/patologia , Neoplasias Vulvares/cirurgiaRESUMO
OBJECTIVES: This study was designed to measure the direct medical charges for patients with and without diabetes who experience myocardial infarction. METHODS: We completed a retrospective cohort analysis (from the third-party payer perspective) to determine the total direct medical charges (eg, hospitalizations, outpatient visits, pharmacy, and emergency room visits) incurred by an inner city sample of 293 patients during the 12 months following myocardial infarction during the period from January 1993 through February 1997. RESULTS: The 87 patients with diabetes had a higher per patient total direct medical charge (inclusive of initial hospitalization) compared to the 206 patients without diabetes ($18,577 versus $26,414) and approximately $3000 more per person year of observation. Hospitalizations (initial and during the follow-up period) accounted for 88% of the total direct medical charges. The mean charge for the initial hospitalization was higher for patients with diabetes ($12,730 versus $15,394). In a subset, the mean charge per cardiovascular-related hospitalization that occurred during the follow-up period was also higher for patients with diabetes ($6344 versus $9648). CONCLUSIONS: Consistent with what we expected, patients with diabetes incurred higher total direct medical charges as a result of and following myocardial infarction. These data can be used in future cost-effectiveness evaluations for therapies developed to treat patients with diabetes who experience myocardial infarction or for therapies designed to reduce the risk of macrovascular complications associated with diabetes.
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Diabetes Mellitus/economia , Custos Diretos de Serviços/estatística & dados numéricos , Preços Hospitalares/estatística & dados numéricos , Hospitalização/economia , Infarto do Miocárdio/economia , Adulto , Idoso , Comorbidade , Complicações do Diabetes , Feminino , Mortalidade Hospitalar , Hospitalização/estatística & dados numéricos , Humanos , Indiana , Seguro Saúde , Tempo de Internação/economia , Masculino , Prontuários Médicos , Pessoa de Meia-Idade , Análise Multivariada , Infarto do Miocárdio/complicações , Infarto do Miocárdio/mortalidade , Estudos Retrospectivos , População UrbanaRESUMO
OBJECTIVE: To describe antipsychotic medication use patterns in an inner-city, outpatient population of indigent patients with schizophrenia. METHODS: This retrospective cohort study used the Regenstrief Medical Record System to identify schizophrenic patients receiving antipsychotic medication(s). Patients were included and identified as initiating a new treatment episode if they did not receive any antipsychotic prescription for 90 days before their first antipsychotic prescription in 1995. Each patient was followed for 1 year. RESULTS: Three hundred and sixteen patients met study criteria. Typical and atypical (clozapine and risperidone) antipsychotic agents were selected as initial therapy in 88% and 12% patients, respectively. The majority of patients (71.5%) were exposed to only one antipsychotic agent during their treatment year. Approximately 25% of all patients switched from one antipsychotic to a different antipsychotic during 12 months of therapy. Nearly 90% of patients augmented their prescribed antipsychotic with a concomitant medication during the 12-month study period. Approximately 30% of the cohort received treatment with an antipsychotic for 12 continuous months and were, thus, classified as having stable antipsychotic therapy. The majority of patients (67.1%) had periods of interrupted therapy (range, 1-11 months) during the 12 month study period. CONCLUSION: As of 1995 an overwhelming majority of schizophrenic patients in this indigent, inner-city population initiated therapy with a typical antipsychotic. Patients frequently switched antipsychotics and discontinued their therapy during the 1 year study period. Reasons for switching or discontinuing may include the following: ineffective therapy; patient intolerance; change in symptoms; and improved assessment and understanding of the diagnosis or physician preference.
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Antidepressivos Tricíclicos/uso terapêutico , Antipsicóticos/uso terapêutico , Uso de Medicamentos/estatística & dados numéricos , Esquizofrenia/tratamento farmacológico , Adulto , Estudos de Coortes , Feminino , Humanos , Indiana , Masculino , Indigência Médica , Pacientes Ambulatoriais , Polimedicação , Estudos Retrospectivos , Esquizofrenia/classificação , População UrbanaRESUMO
PURPOSE: Psychiatric morbidity is common in cancer patients toward the end of life. In this study, we demonstrate the use of an electronic patient record system to identify patients with advanced cancer, and then analyze practice patterns regarding the use of antidepressants. PATIENTS AND METHODS: Using electronic patient records from January 1986 to December 1996, we identified 17,476 patients with possible cancer. Patients were identified by virtue of having any one of eight markers. We used an iterative process to modify the specificity of these markers, and an advanced cancer cohort was assembled consisting of 1185 patients. RESULTS: A random sample of 200 written medical records were reviewed, of which 157 records (78.5%) were retrieved. Extracted information was reviewed by an oncologist, and patients were classified as follows: (1) no evidence of cancer; (2) evidence of cancer with an expected survival of less than or equal to 24 months; or (3) evidence of cancer with an expected survival of more than 24 months. Overall, 86% of the advanced cancer sample assembled from electronic records was correctly classified as advanced cancer by the review of the written records. Overall, 16% of all 1185 patients with advanced cancer were exposed to at least one antidepressant, with 3% of patients exposed to a selective serotonin-reuptake inhibitor, 10% exposed to a tricyclic antidepressant at a dose of greater than 25 mg, and 4% exposed to a low dose of a tricyclic antidepressant. CONCLUSION: The electronic patient record can be used to assemble an advanced cancer cohort for the purpose of studying palliative care practice patterns. Antidepressants are seldom part of the palliative management of this population.
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PURPOSE: Though case management has been recommended to improve the outcomes of patients with costly or morbid conditions, it has seldom been studied in controlled trials. We performed a randomized, controlled clinical trial of an intensive, multidisciplinary case management program for patients with chronic renal insufficiency and followed patients for 5 years. PATIENTS AND METHODS: We enrolled 437 primary-care patients (73% of those eligible) with chronic renal insufficiency (estimated creatinine clearance consistently < 50 mL/min with the last serum creatinine level > 1.4 mg/dL) who were attending an urban academic general internal medicine practice. The intensive case management, administered during the first 2 years after enrollment, consisted of mandatory repeated consultations in a nephrology case management clinic staffed by two nephrologists, a renal nurse, a renal dietitian, and a social worker. Control patients received usual care. Primary outcome measurements included serum creatinine level, estimated creatinine clearance, health services use, and mortality in the 5 years after enrollment. Secondary measures included use of renal sparing and potentially nephrotoxic drugs. RESULTS: There were no differences in renal function, health services use, or mortality in the first, second, or third through fifth years after enrollment. There were significantly more outpatient visits among intervention patients, mainly because of the added visits to the nephrology case management clinic. There were also no significant differences in the use of renal sparing or selected potentially nephrotoxic drugs. The annual direct costs of the intervention were $89,355 ($484 per intervention patient). CONCLUSION: This intensive, multidisciplinary case-management intervention had no effect on the outcomes of care among primary-care patients with established chronic renal insufficiency. Such expensive and intrusive interventions, despite representing state-of-the-art care, should be tested prospectively before being widely introduced into practice.
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Administração de Caso , Medicina de Família e Comunidade , Falência Renal Crônica/terapia , Nefrologia , Idoso , Instituições de Assistência Ambulatorial , Terapia Combinada/economia , Feminino , Seguimentos , Humanos , Indiana , Falência Renal Crônica/economia , Masculino , Pessoa de Meia-Idade , Encaminhamento e Consulta , Resultado do TratamentoRESUMO
OBJECTIVE: To determine the medical charges for treating diabetic ketoacidosis (DKA) episodes relative to direct medical care charges of adult patients with type I diabetes. RESEARCH DESIGN AND METHODS: Using data from an electronic medical record system, we identified adult patients with type I diabetes who had received inpatient or outpatient care on at least two occasions between 1 January 1993 and 30 June 1994. Resources and charges for hospitalizations, emergency room visits, outpatient visits, and pharmaceuticals were recorded during this period. One additional year of information was collected to assess the resources and charges associated with multiple DKA episodes. RESULTS: A total of 200 patients were identified, of whom 72 (36.0%) experienced a total of 161 DKA episodes. The direct medical care charges associated with DKA episodes represented 28.1% of the direct medical care charges for the cohort of patients with type I diabetes. The average charge per DKA episode was $6,444. The estimated annual medical care charge for each patient was $7,855 ($13,096 per patient experiencing a DKA episode versus $4,907 per patient not experiencing an episode). Multiple DKA episodes were experienced by 24 (12.0%) of the study patients and accounted for 55.6% of the direct medical care charges for these patients. CONCLUSIONS: DKA episodes represented more than $1 of every $4 spent on direct medical care for adult patients with type I diabetes and $1 of every $2 in those patients experiencing multiple episodes. Interventions that are capable of even a modest reduction in the number of DKA episodes could produce substantial cost savings in a health care system and could be particularly cost-effective in adult patients with recurrent DKA.
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Diabetes Mellitus Tipo 1/economia , Cetoacidose Diabética/economia , Custos de Cuidados de Saúde/estatística & dados numéricos , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/etnologia , Cetoacidose Diabética/etnologia , Cuidado Periódico , Etnicidade , Feminino , Custos de Cuidados de Saúde/classificação , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Estados UnidosRESUMO
BACKGROUND: Previous studies have documented greater use of health services by depressed persons and have postulated that health care costs could be reduced overall through better recognition and treatment of depression. OBJECTIVE: To determine whether a greater burden of medical illness contributes to excess charges for diagnostic tests among older adults with symptoms of depression. DESIGN: Prospective cohort study. SETTING: A primary care group practice at an academic institution. PATIENTS: 3767 patients 60 years of age and older who completed testing on the Centers for Epidemiologic Studies Depression Scale (CES-D) during routine office visits. MEASUREMENTS: Charges for all inpatient and ambulatory diagnostic testing for 2 years, including clinical pathology, diagnostic imaging, and special procedures; number of visits to the ambulatory care center or emergency department; and number of hospitalizations. The Ambulatory Care Group case-mix approach, which is based on ambulatory diagnoses, was used as a measure of health status and expected resource consumption. RESULTS: Patients with symptoms of depression (CES-D scores > or = 16) were significantly younger (66.6 compared with 68.1 years; P < 0.001), more likely to be white (50.5% compared with 33.9%; P = 0.001), and more likely to be female (75.8% compared with 67.6%; P = 0.001) than were those without these symptoms (CES-D scores < 16). They also had more nonpsychiatric comorbid conditions, had more visits to the ambulatory care center (9.2 compared with 7.8; P < 0.001), were more likely to use the emergency department (52.3% compared with 40%; P = 0.001), were more likely to be hospitalized (22.4% compared with 17%; P = 0.002), and had greater median total diagnostic test charges for a period of 1 year ($583 compared with $387; P < 0.001). The difference in charges, most of which were clinical pathology charges (54.2%), persisted into the second year. Ambulatory Care Group assignment was independently associated with diagnostic test charges. The CES-D summary score was not independently associated with diagnostic test charges when controlling for Ambulatory Care Group assignment. CONCLUSIONS: Patients with symptoms of depression accrue greater average diagnostic test charges. However, these data suggest that such patients also have a greater burden of comorbid nonpsychiatric illness. Efforts to improve outcome and decrease cost for patients who have late-life depression must target interventions to improve the care of psychiatric and medical illness concurrently.
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Idoso/psicologia , Depressão/economia , Testes Diagnósticos de Rotina/economia , Idoso de 80 Anos ou mais , Comorbidade , Testes Diagnósticos de Rotina/estatística & dados numéricos , Feminino , Serviços de Saúde/economia , Serviços de Saúde/estatística & dados numéricos , Humanos , Masculino , Estudos ProspectivosRESUMO
The potency and reversibility of a new orally active 5-lipoxygenase (5-LO) inhibitor were evaluated in human volunteers. Zileuton (A-64077) 600 mg q.i.d. was administered to volunteers for 14 days in a phase I study, and blood samples were withdrawn, stimulated with ionophore A23187 and LTB4 levels were determined using both reverse phase high performance liquid chromatography (RP-HPLC) and radioimmunoassay (RIA). The drug significantly inhibited (above 70%) LTB4 biosynthesis in whole blood stimulated with A-23187 throughout the 14 days. The activity of 5-LO was also measured one week after stopping the medication and was returned to control levels. Measurement of LTB4 levels using either RP-HPLC or RIA gave similar percentage of inhibition although RIA appeared to underestimate by half the absolute amounts of LTB4 in the blood samples. These results show that Zileuton is a highly active and reversible 5-LO inhibitor in human.
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Araquidonato 5-Lipoxigenase/sangue , Hidroxiureia/análogos & derivados , Inibidores de Lipoxigenase/farmacologia , Adolescente , Adulto , Calcimicina/farmacologia , Cromatografia Líquida de Alta Pressão , Método Duplo-Cego , Humanos , Hidroxiureia/farmacologia , Técnicas In Vitro , Leucotrieno B4/sangue , Inibidores de Lipoxigenase/sangue , Masculino , Pessoa de Meia-Idade , RadioimunoensaioRESUMO
The effect of a single oral dose (800 mg) of zileuton (A-64077), a specific 5-lipoxygenase inhibitor, on the early and late airway responses to inhaled allergen was studied in a randomised, double blind, placebo controlled, and crossover trial in nine subjects with atopic asthma. Leukotriene generation was also assessed in vivo by measuring urinary leukotriene (LT) E4 excretion, and ex vivo by measuring calcium ionophore stimulated whole blood LTB4 production. Zileuton almost completely inhibited ex vivo LTB4 production but reduced urinary excretion of LTE4 by only about half. There was a trend for the early asthmatic response to be less on the day of zileuton treatment, but this did not reach statistical significance (p = 0.08). The zileuton induced reduction in maximum fall in FEV1 in the early asthmatic response was, however, significantly related to the reduction in urinary LTE4 excretion (r = 0.8), but not to the reduction in LTB4 generation ex vivo. There was no significant change in the allergen induced late asthmatic response, or in the increase in airway responsiveness to methacholine following antigen. The results provide some support for the hypothesis that the cysteinyl leukotrienes have a role in the allergen induced early asthmatic response. More complete in vivo inhibition of 5-lipoxygenase may be needed to produce a significant reduction in airway response to allergen challenge.
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Asma/imunologia , Volume Expiratório Forçado/efeitos dos fármacos , Hidroxiureia/análogos & derivados , Inibidores de Lipoxigenase , SRS-A/análogos & derivados , Adulto , Alérgenos/imunologia , Asma/sangue , Método Duplo-Cego , Humanos , Hidroxiureia/farmacologia , Leucotrieno B4/sangue , Leucotrieno E4 , Masculino , SRS-A/urina , Fatores de TempoRESUMO
The histologic and histochemical features of quinolone-induced arthropathy were studied using 14 skeletally immature Beagle dogs (3 to 4 months old) dosed orally with difloxacin at 300 mg/kg body weight once daily for 1, 2, 5, or 7 days. A placebo was given to eight other age-matched Beagle dogs that served as controls. A scoring technique that included lesion size and histologic features was used to determine the progression of lesions. Articular-epiphyseal cartilage complexes on the femoral and humeral heads and tibial tarsal bone were identified as predilection sites. Within predilection sites on femoral and humeral heads, lesions developed in specific areas. Lesions appeared within 2 days of the onset of treatment, and lesion scores increased with time. Grossly, the lesions were raised, fluid-filled vesicles on the articular surface. Histologic changes included vesicle formation with loss of proteoglycan, clumping of unmasked collagen, and degeneration and necrosis of chondrocytes. In lesions with higher scores, chondrocytes were often in clusters or they were undergoing metaplasia toward spindle-shaped cells. Although dissolution of matrix and necrosis of chondrocytes were typical of all lesions, smaller lesions had histologically normal chondrocytes adjacent to small vesicles. In sections stained with toluidine blue, proteoglycan was aggregated with collagen fibrils or was absent from the matrix adjacent to vesicles. Unique features, such as biomechanical forces, may predispose specific areas of articular cartilage to develop lesions.
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Anti-Infecciosos , Osso e Ossos/efeitos dos fármacos , Cartilagem Articular/efeitos dos fármacos , Ciprofloxacina/análogos & derivados , Cães , Fluoroquinolonas , Fatores Etários , Animais , Osso e Ossos/patologia , Cartilagem Articular/patologia , Condroitina/metabolismo , Ciprofloxacina/toxicidade , Feminino , Cabeça do Fêmur/efeitos dos fármacos , Cabeça do Fêmur/patologia , Úmero/efeitos dos fármacos , Úmero/patologia , Masculino , Proteoglicanas/metabolismoRESUMO
Tulobuterol hydrochloride (HCl) has beta 2-adrenergic agonist activity and is under development for use in the treatment of chronic obstructive lung disease. The purpose of this study was to determine the toxicity of inhaled tulobuterol HCl in rats and dogs. Rats were whole-body exposed to aerosol gravimetric concentrations of 0, 0.03, 0.22, or 1.1 mg/liter of tulobuterol HCl, 60 min/day for 28 days. Dogs were exposed (via insufflation) to estimated daily doses of 0, 0.2, 1.0, or 6.0 mg/kg for an equal period. Plasma levels of tulobuterol were determined following exposure on Days 1, 8, and 28 using a high-pressure liquid chromatographic method developed for this study. Results indicated that plasma tulobuterol levels were highly correlated with tulobuterol doses (p less than 0.001 for rats and dogs). No dose-related changes in body weight food consumption, hematological, or serum chemistry parameters were observed in either species. Anterior nasal cavity lesions were observed by light microscopy in rats exposed to 0.22 and 1.1 mg/liter tulobuterol HCl at an incidence of 14 and 93%, respectively. These lesions involved the nasal septum, turbinates, and/or the dorsolateral wall of the nasal cavity and consisted of suppurative rhinitis and necrosis. The corresponding mean plasma tulobuterol levels on Day 28 in mid- and high-dose rats were approximately 1000 and 15,000 ng/ml. Nasal lesions were not observed in rats allowed to recover for 2 weeks. No gross or microscopic lesions were detected in lungs or other tissues of either species.(ABSTRACT TRUNCATED AT 250 WORDS)
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Agonistas Adrenérgicos beta/toxicidade , Terbutalina/análogos & derivados , Administração por Inalação , Agonistas Adrenérgicos beta/administração & dosagem , Agonistas Adrenérgicos beta/farmacocinética , Animais , Cromatografia Líquida de Alta Pressão , Cães , Feminino , Masculino , Mucosa Nasal/efeitos dos fármacos , Mucosa Nasal/patologia , Tamanho da Partícula , Ratos , Ratos Endogâmicos , Terbutalina/administração & dosagem , Terbutalina/farmacocinética , Terbutalina/toxicidadeRESUMO
We tested the hypothesis that a drop in metabolic rate (MR) causes the apneas observed in some subjects during transcendental meditation (TM). We measured O2 consumption (VO2) and CO2 production (VCO2) in three groups of experienced meditators and one group of nonmeditating controls. Measurements were made before, during, and after TM for the meditators and before, during, and after eyes-closed relaxation for the nonmeditating controls. The three groups of meditators consisted of 1) those showing little change in the frequency of ventilation (f) with meditation, 2) those showing a marked decline in f, and 3) those showing numerous apneas and a marked fall in f. There were significant trial effects but no group or interaction effects for the decline in VO2. Thus we concluded that a drop in MR is not the cause of the apneas. However, there were significant trial and interaction effects for the changes in VCO2 and the respiratory exchange ratio (R), with a significant drop in R for the meditators but not for the controls. We report additional evidence and speculate that the drop in R is a consequence of mild hypoventilation.
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Apneia/fisiopatologia , Metabolismo Basal , Terapia de Relaxamento , Respiração , Adulto , Apneia/psicologia , Dióxido de Carbono/sangue , Feminino , Humanos , Masculino , Oxigênio/sangue , Consumo de Oxigênio , Valores de ReferênciaRESUMO
3-O-demethylfortimicin A disulfate (ODMF), a novel aminocyclitol antibiotic, was administered subcutaneously for three months to groups of male and female cats at 15, 30 or 60 mg base/kg/day. Gentamicin sulfate (GS) at doses of 6 and 13 mg base/kg/day served as a reference compound. Signs of vestibular toxicity were considered to include persistent unsteady gait and stance, impaired righting reflex and abnormally diminished postrotatory vestibular nystagmus. Renal toxicities produced by ODMF and GS were also determined and compared. ODMF at 15 and 30 mg base/kg/day produced no signs of vestibular toxicity, while a dosage of 60 mg base/kg/day of ODMF produced vestibular toxicity in 7/10 cats. Three affected male cats died or were killed in moribund condition between study days 49 and 64. Vestibular toxicity was observed in 10/10 cats treated with GS at 13 mg base/kg/day and in 3/10 cats at 6 mg base/kg/day. All ten cats treated with GS at 13 mg base/kg/day died or were killed in moribund condition between study days 30 and 81. The deaths and moribundity in cats treated with ODMF or GS were attributed to renal toxicity. The vestibular toxicity and nephrotoxicity produced by ODMF and GS were more severe in male cats than in females. In conclusion, ODMF given at doses up to 60 mg base/kg/day for three months induced comparatively less vestibular toxicity and renal pathology than did GS at a dose of 13 mg base/kg/day.
Assuntos
Aminoglicosídeos , Antibacterianos/toxicidade , Gentamicinas/toxicidade , Vestíbulo do Labirinto/efeitos dos fármacos , Animais , Antibacterianos/sangue , Gatos , Feminino , Gentamicinas/sangue , Injeções Subcutâneas , Rim/patologia , MasculinoRESUMO
In the late 1960s the artificial sweetener cyclamate was implicated as a bladder carcinogen in rats. This finding and other concerns about its safety ultimately led to a ban on cyclamate in the U.S. and restrictions on its use in many other countries. Since that time, the carcinogenic potential of cyclamate and cyclohexylamine, its principal metabolite, has been reevaluated in a group of well-controlled, well-designed bioassays that have failed to substantiate the earlier findings. This review of the published and unpublished literature on cyclamate attempts to evaluate the carcinogenicity question and other important aspects of the toxicity of cyclamate and cyclohexylamine, including their effects on various organ systems, their genotoxic potential, and their effects on reproduction. In addition, the physiological disposition of cyclamate is reviewed, with particular attention directed toward the site and extent of its conversion to cyclohexylamine.
Assuntos
Ciclamatos/toxicidade , Cicloexilaminas/toxicidade , Anormalidades Induzidas por Medicamentos/etiologia , Absorção , Glândulas Suprarrenais/efeitos dos fármacos , Animais , Bactérias/metabolismo , Sangue/efeitos dos fármacos , Glicemia/análise , Embrião de Galinha , Aberrações Cromossômicas , Cocarcinogênese , Cricetinae , Ciclamatos/metabolismo , Cicloexilaminas/metabolismo , Sistema Digestório/efeitos dos fármacos , Feminino , Células Germinativas/efeitos dos fármacos , Células Germinativas/ultraestrutura , Coração/efeitos dos fármacos , Humanos , Técnicas In Vitro , Intestinos/microbiologia , Rim/efeitos dos fármacos , Dose Letal Mediana , Fígado/efeitos dos fármacos , Neoplasias Hepáticas/induzido quimicamente , Neoplasias Pulmonares/induzido quimicamente , Linfoma não Hodgkin/induzido quimicamente , Macaca mulatta , Masculino , Metilnitrosoureia , Camundongos , Testes de Mutagenicidade , Mutagênicos , Mutação , Neoplasias Experimentais/induzido quimicamente , Pâncreas/efeitos dos fármacos , Gravidez , Coelhos , Ratos , Ratos Endogâmicos , Reprodução/efeitos dos fármacos , Simpatomiméticos/toxicidade , Testículo/efeitos dos fármacos , Glândula Tireoide/efeitos dos fármacos , Distribuição Tecidual , Neoplasias da Bexiga Urinária/induzido quimicamenteRESUMO
The acute LD50 for 3-O-demethylfortimicin A disulfate (ODMF) in mice and rats were 419 and 778 mg activity/kg (dosages are expressed in terms of antibiotic activity (potency), rather than on a weight basis) for single-dose im administration and, 90 and 96 mg activity/kg for single-dose iv administration, respectively. No drug-related gross or microscopic lesions were found in rabbits given single iv infusions of ODMF at dosages of 10 to 400 mg activity/kg. Minimal to mild muscle irritation was seen in rabbits given im concentrations of 3.8 or 7.5% ODMF at dosages of 48 or 93 mg ODMF activity/kg. In 1-month iv studies in dogs treated with ODMF at dosages of 0.4, 1, 4, or 8 mg activity/kg/day, and in concurrent studies in rats treated with ODMF dosages of 1, 3, 6, or 12 mg activity/kg/day, treated animals remained essentially free of adverse effects. In 1-month im studies in dogs treated with ODMF at dosages of 1, 4, 8, or 16 mg activity/kg/day, no renal lesions occurred after an ODMF dosage of 1 mg activity/kg/day. Concurrent im studies in rats treated with ODMF at dosages of 6, 12, 24, or 48 mg activity/kg/day showed that ODMF dosages of 6 and 12 mg activity/kg/day did not produce renal lesions. In 6-month chronic im studies in dogs with ODMF dosages of 0.5, 1, or 4 mg activity/kg/day or gentamicin sulfate (GS) dosages of 2 mg activity/kg/day, and in concurrent studies in rats treated with ODMF dosages of 0.5, 2, or 6 mg activity/kg/day or GS dosages of 3 mg activity/kg/day, less severe local irritation and nephrotoxicity occurred after treatments with ODMF than with GS. In both rats and dogs treated by either the iv or the im route of administration, higher concentrations of ODMF and GS were found in the kidneys than in the sera. Mean serum and tissue concentrations of GS were higher than those of ODMF. Local tissue irritation and nephrotoxicity were lower with ODMF than with GS on a milligram activity per kilogram basis.