Impact Of Low Doses Research Articles

Bisphenol A (BPA) exposure aggravates hepatic oxidative stress and inflammatory response under hypertensive milieu – Impact of low dose on hepatocytes and influence of MAPK and ER stress pathways

Human exposure to the hazardous chemical, Bisphenol A (BPA), is almost ubiquitous. Due to the prevalence of hypertension (CVD risk factor) in the aged human population, it is necessary to explore its adverse effect in hypertensive subjects. The current study exposed the Nω-nitro-l-arginine methyl ester (L-NAME) induced hypertensive Wistar rats to human exposure relevant low dose of BPA (50 μg/kg) for 30 days period. The liver biochemical parameters, histopathology, immunohistochemistry, gene expression (RT-qPCR), trace elements (ICP-MS), primary rat hepatocytes cell culture and metabolomic (1H NMR) assessments were performed. Results illustrate that BPA exposure potentiates/aggravates hypertension induced tissue abnormalities (hepatic fibrosis), oxidative stress, ACE activity, malfunction of the antioxidant system, lipid abnormalities and inflammatory factor (TNF-α and IL-6) expression. Also, in cells, BPA increased ROS generation, mitochondrial dysfunction and lipid peroxidation without any impact on cytotoxicity and caspase 3 and 9 activation. Notably, BPA exposure modulate lipid metabolism (cholesterol and fatty acid) in primary hepatocytes. Finally, the influence of ERK1/2, p38MAPK, ER stress and oxidative stress during relatively high dose of BPA elicited cytotoxicity was observed. Therefore, a precise hazardous risk investigation of BPA exposure in hypertensive populations is highly recommended.

Dynamics of in vitro rumen methane production after nitrate addition

ABSTRACT The present study aimed to assess the dynamics of rumen methane (CH4) production following the addition of NaNO3. This was done using an in vitro rumen fermentation system that ensures continuous gas and methane assessments. Four different levels of NaNO3 were used to get the final nitrate concentrations of 0.5, 1.0, 1.5, and 2.0 mg/ml of rumen fluid. For each dose, corresponding controls contained sodium chloride and urea were realised to ensure comparable levels of sodium and nitrogen. The addition of nitrates had slight effect on the intensity of fermentation because the total gas produced minus CH4 (total methane-free gas) only went down at the highest dose (2.0 mg/ml), and the final concentrations of SCFA were the same at all doses. The most evident effect was a modification of the SCFA profile (low concentrations of propionate and valerate, progressive increments of acetate, and decreases of butyrate) and a reduction in overall CH4 production. The CH4 yield for the 0.5 mg/ml dose was not different from control in the entire fermentation. Yield of the 1.0 mg/ml dose was significantly lower than the control group (p < 0.05) only within the initial 24-h period, and higher dosages (1.5 and 2.0 mg/ml) were lower during the entire fermentation (p < 0.01). Methane yields were well fitted with the Gompertz model, but only the highest level of nitrate inclusion had a significant impact on the majority of model parameters (p < 0.01). The linear regressions between CH4 yields (y) and the amounts of nitrates (x) at progressive fermentation durations (e.g. 6, 12, 24, and 48 h) produced equations with increasing absolute slopes (from −0.069 to −0.517 ml/mg of nitrate). Therefore, nitrate reduced rumen CH4 yield in a dose-dependent manner: the impact of low doses was primarily observed at the initial stages of fermentation, whereas high doses exhibited effectiveness throughout the entire fermentation process. In conclusion, in batch fermentation systems, the dose effect of nitrates on methane yield was time dependent.

Daily Glucocorticoid Replacement Dose in Adrenal Insufficiency, a Mini Review.

The Endocrine Society Guidelines and recent reviews of adrenal insufficiency (AI) recommend a daily glucocorticoid replacement dose of 15 to 25 mg with a midpoint of 20 mg of hydrocortisone (HC) (alternatively 3 to 5 mg prednisolone) in divided doses in otherwise healthy individuals with AI. In contrast, a daily glucocorticoid replacement dose of 4.3 to 26 mg/d HC with a midpoint of 15 mg/d is predicted from current measurements of daily cortisol production rates and oral HC bioavailability. The higher HC doses recommended in the current guidelines may result in glucocorticoid overtreatment of some AI patients and associated long-term adverse outcomes. A titration method for determination of the individual patient’s daily glucocorticoid replacement dose and the impact of lower doses are reviewed. Future related research questions are identified.

GRAPHENE OXIDE AFFECT THE EXPRESSION OF PROLIFERATION RELATED GENES AND microRNA IN NORMAL HUMAN ASTROCYTES

Aim. In this study we investigate the impact of low doses of graphene oxide on the expression of key regulatory genes which control cell proliferation as well as microRNAs in normal human astrocytes. Methods. The expression level of genes related to cell proliferation was studied by real-time qPCR in normal human astrocytes line NHA/TS (Cambrex Bio Science, Walkersville, MD, USA) using SYBRGreen Mix and specific for each mRNA forward and reverse primers. These astrocytes were treated with graphene oxide (1 and 4 ng/ml of medium) for 24 hrs. Graphene oxide (2 mg/ml, dispersion in water) was received from Sigma-Aldrich Chemie GmbH, Germany. Total RNA was extracted using TRIZOL reagent. For reverse transcription of mRNAs we used Thermo Scientific Verso cDNA Synthesis Kit (Germany). The values of mRNA expressions were normalized to the level of ACTB mRNA and represented as percent of control (100 %). For polyadenylation and reverse transcription of miRNAs we used Mir-X miRNA First-Strand Synthesis Kit (Takara, Japan). The expression level of microRNAs was studied by real-time qPCR using SYBRGreen Mix and specific for each miRNA forward primers and universal reverse primer. For normalization of microRNA expressions the level of U6 RNA expression was used. Results. It was shown that the expression level of TOB1, HSPA5, EDEM1, MYBL1, and MYBL2 significantly increased in normal human astrocytes line NHA/TS, which were treated with graphene oxide (1 and 4 ng/ml of medium) for 24 hrs. Up-regulation of these genes expression was dose-dependent: bigger dose of graphene oxide (4 ng/ml of medium) introduced more significant changes in the expression of all these genes. Furthermore, bioinformatics analysis of 3′-untranslated regions of mRNA allowed identifying binding sites of microRNA: miR-19a for MYBL1, miR-143 for MYBL2 and miR-182 for TOB1. It was also shown that the expression of all these microRNA significantly down-regulated by graphene oxide, supporting the idea of both post-transcriptional and transcriptional regulation of MYBL1, MYBL2 and TOB1 gene expressions. Conclusions. Graphene oxide significantly disturbs genome stability by up-regulation of the expression of key regulatory genes and down-regulation of microRNA.

Impact of Low Dose Maltodextrin/Citrulline Loading on the Severity and Duration of Stress Induced Hyperglycemia in Cardiac Surgery

Impact of Low Dose Maltodextrin/Citrulline Loading on the Severity and Duration of Stress Induced Hyperglycemia in Cardiac Surgery

Dose threshold for radiation induced fetal programming in a mouse model at 4 months of age: Hepatic expression of genes and proteins involved in glucose metabolism and glucose uptake in brown adipose tissue.

Exposure to ionizing radiation contributing to negative health outcomes is a widespread concern. However, the impact of low dose and sub-lethal dose radiation (SLDR) exposures remain contentious, particularly in pregnant women who represent a vulnerable group. The fetal programming hypothesis states that an adverse in utero environment or stress during development of an embryo or fetus can result in permanent physiologic changes often resulting in progressive metabolic dysfunction with age. To assess changes in gene expression profiles of glucose/insulin signaling and lipid metabolism caused by radiation exposure in utero, pregnant C57Bl/6J mice were irradiated using a dose response ranging from low dose to SLDR and compared to a Sham-irradiated group. mRNA expression analysis in 16 week old offspring (n = 84) revealed that genes involved in metabolic function including glucose metabolism, insulin signaling and lipid metabolism were unaffected by prenatal radiation exposures up to 300 mGy. However, female offspring of dams exposed to 1000 mGy had upregulated expression of genes contributing to insulin resistance and gluconeogenesis. In a second cohort of mice, the effects of SLDR on fetal programming of hepatic SOCS3 and PEPCK protein expression were assessed. 4 month old female offspring of dams irradiated at 1000 mGy had: 1) increased liver weights, 2) increased hepatic expression of proteins involved in glucose metabolism and 3) increased 18F-fluorodeoxyglucose (FDG) uptake in interscapular brown adipose tissue (IBAT) measured by positron emission tomography (PET) (n = 25). The results of this study indicate that prenatal radiation exposure does not affect metabolic function up to 300 mGy and 1000 mGy may be a threshold dose for sex-specific alterations in glucose uptake and hepatic gene and protein expression of SOCS3, PEPCK, PPARGC1A and PPARGC1B. These findings suggest that SLDR doses alter glucose uptake in IBAT and hepatic gene and protein expression of offspring and these changes may progress with age.

Role of synergy and immunostimulation in design of chemotherapy combinations: An analysis of doxorubicin and camptothecin.

Combination chemotherapy is often employed to improve therapeutic efficacies of drugs. However, traditional combination regimens often utilize drugs at or near‐their maximum tolerated doses (MTDs), elevating the risk of dose‐related toxicity and impeding their clinical success. Further, high doses of adjuvant or neoadjuvant chemotherapies can cause myeloablation, which compromises the immune response and hinders the efficacy of chemotherapy as well as accompanying treatments such as immunotherapy. Clinical outcomes can be improved if chemotherapy combinations are designed to reduce the overall doses without compromising their therapeutic efficacy. To this end, we investigated a combination of camptothecin (CPT) with doxorubicin (DOX) as a low‐dose treatment option for breast cancer. DOX‐CPT combinations were synergistic in several breast cancer cell lines in vitro and one particular ratio displayed extremely high synergy on human triple negative breast cancer cells (MDA‐MB‐231). This combination led to excellent long‐term survival of mice bearing MDA‐MB‐231 tumors at doses roughly five‐fold lower than the reported MTD values of its constituent drugs. Impact of low dose DOX‐CPT treatment on local tumor immune environment was assessed in immunocompetent mice bearing breast cancer (4T1) tumors. The combination was not only superior in inhibiting the disease progression compared to individual drugs, but it also generated a more favorable antitumor immunogenic response. Engineering DOX and CPT ratios to manifest synergy enables treatment at doses much lower than their MTDs, which could ultimately facilitate their translation into the clinic as a promising combination for breast cancer treatment.

The effect of hydroalcoholic extract of Cannabis Sativa on morphology and growth of bone marrow mesenchymal stem cells in rat

Background:One of the most important issues in cellular therapies is the examination of stem cells in different conditions. Given the increasing use of herbal drugs and herbal medicines and the potential effects of herbs on various diseases, the study of stem cells in the mediums of these compounds seems to be necessary.Aims:The current paper was to evaluate the effect of cannabis sativa extract on morphology, growth and maintenance of the characteristics of rat bone marrow stem cells.Methods:In this study, rat bone marrow mesenchymal stem cells were used. The effect of cannabis extract in different concentrations on cell morphology was investigated through microscopic observations and cytogenetic methods. In the context of the study of bioavailability and growth process, we used the mtt assay test and calculated the cell population doubling time and the growth curve plotting.Results:The results show that cannabis extract increases the proliferation of rat bone marrow mesenchymal stem cells compared to control group. Also, the effect of cannabis extract is dependent on its dose. The treated cells with a concentration of 100 ng / ml cannabis extract had the highest growth rate compared to control (P˂.050).Conclusion:Given the increasing impact of low doses of cannabis extract on the growth of bone marrow mesenchymal stem cells, it seems that the use of effective ingredients in this plant extract is beneficial for cell-therapeutic purposes in autoimmune diseases. On the other hand, higher doses cause cell death and an increase in apoptosis, so, in people consuming these substances, they will decrease the proliferation of stem cells due to increased concentration of substances in the body.

Impact of micropollutants on the life-history traits of the mosquito Aedes aegypti: On the relevance of transgenerational studies

Hazard assessment of chemical contaminants often relies on short term or partial life-cycle ecotoxicological tests, while the impact of low dose throughout the entire life cycle of species across multiple generations has been neglected. This study aimed at identifying the individual and population-level consequences of chronic water contamination by environmental concentrations of three organic micropollutants, ibuprofen, bisphenol A and benzo[a]pyrene, on Aedes aegypti mosquito populations in experimental conditions. Life-history assays spanning the full life-cycle of exposed individuals and their progeny associated with population dynamics modelling evidenced life-history traits alterations in unexposed progenies of individuals chronically exposed to 1 μg/L ibuprofen or 0.6 μg/L benzo[a]pyrene. The progeny of individuals exposed to ibuprofen showed an accelerated development while the progeny of individuals exposed to benzo[a]pyrene showed a developmental acceleration associated with an increase in mortality rate during development. These life-history changes due to pollutants exposure resulted in relatively shallow increase of Ae. aegypti asymptotic population growth rate. Multigenerational exposure for six generations revealed an evolution of population response to ibuprofen and benzo[a]pyrene across generations, leading to a loss of previously identified transgenerational effects and to the emergence of a tolerance to the bioinsecticide Bacillus turingiensis israelensis (Bti). This study shed light on the short and long term impact of environmentally relevant doses of ibuprofen and benzo[a]pyrene on Ae. aegypti life-history traits and insecticide tolerance, raising unprecedented perspectives about the influence of surface water pollution on vector-control strategies. Overall, our approach highlights the importance of considering the entire life cycle of organisms, and the necessity to assess the transgenerational effects of pollutants in ecotoxicological studies for ecological risk assessment. Finally, this multi-generational study gives new insight about the influence of surface water pollution on microevolutionary processes.

Multiple low doses of erythropoietin delay the proliferation of hepatocytes but promote liver function in a rat model of subtotal hepatectomy

The impact of various doses of erythropoietin (EPO) on liver regeneration after partial hepatectomy (PH) in different animal models is still under debate. We investigated the impact of low doses of EPO on liver regeneration in a rat model of subtotal hepatectomy. We established a 90 % PH rat model with perioperative injections of low-dose EPO (1,000 IU/kg). We analyzed survival and hepatocyte proliferation in animals treated with or without EPO and assessed liver function by blood ammonia measurement and the indocyanine green 15-min retention test. Low doses of EPO treatment improved the survival of rats after 90 % PH. Unexpectedly, during the first 24 h after the operation, liver regeneration in the EPO-treated rats was inhibited. DNA synthesis, cell proliferation, and the expression of cyclins and p-STAT3 peaked 48 h after PH, which was delayed by about 24 h vs. the control rats. Furthermore, EPO treatment increased the serum level of IL-6 and protected the hepatocytes from apoptosis. Low doses of EPO do not stimulate early hepatocyte proliferation in the regenerating liver, but contribute to liver protection by inducing IL-6 and inhibiting apoptosis.

Tomothérapie hélicoïdale dans le traitement du mésothéliome pleural malin : impact des faibles doses sur la toxicité pulmonaire et œsophagienne

PurposeTo evaluate the adjuvant treatment of malignant pleural mesothelioma by helical tomotherapy and the impact of low doses on esophageal and pulmonary toxicity. Patients and methodsBetween June 2007 and May 2011, 29 patients diagnosed with malignant pleural mesothelioma received adjuvant radiotherapy by helical tomotherapy. The median age was 63 years (34–72). Histologically, 83 % of patients had epithelioid malignant pleural mesothelioma. Clinically, 45 % of patients were T3 and 55 % N0. Eighty six percent of the patients were treated by extrapleural pneumonectomy and 35 % received neoadjuvant chemotherapy with platinum and pemetrexed. The median dose in the pneumonectomy cavity was 50Gy at 2Gy/fraction. ResultsThe mean follow-up was 2.3 years after diagnosis. Overall survival at 1 and 2 years was 65 and 36 % respectively. The median survival from diagnosis was 18 months. Median lung volumes receiving 2, 5, 10, 13, 15 and 20Gy (V2, V5, V10, V13, V15 and V20) were 100, 98, 52, 36, 19 and 5 %. The median of the mean remaining lung dose was 11Gy. Two patients died of pulmonary complications, three patients had grade 3 lung toxicity, while esophageal grade 3–4 toxicity was observed in three other patients. No significant impact of clinical characteristics and dosimetric parameters were found on pulmonary toxicity, however a V10≥50 %, a V15≥15 % and mean lung dose of 10Gy or more had a tendency to be predictive of pulmonary toxicity (P<0.1). Moreover, in our analysis, the mean lung dose seems to have a significant impact on esophageal toxicity (P=0.03) as well as low doses to the controlateral lung: V5, V10 and V13 (P<0.05). ConclusionHelical tomotherapy is a promising technique in the multimodality treatment of malignant pleural mesothelioma. Low doses received by the contralateral lung appear to be the limiting factor. A dosimetric comparison with volumetric modulated arctherapy techniques would be interesting in this setting.

The effects of aripiprazole on the subscales of the Kellner Symptom Questionnaire in treatment resistant depression

We have recently examined the efficacy of low-dose aripiprazole augmentation for major depressive disorder (MDD), with modest nonsignificant benefit found. In a secondary investigation, we examined whether aripiprazole resulted in improvement in four subscales (depression, anxiety, somatic symptoms, and hostility) of the Kellner Symptom Questionnaire (KSQ). We reanalyzed data from the main outcome study on 221 MDD patients with inadequate response to selective serotonin reuptake inhibitors or serotonin-norepinephrine reuptake inhibitors. Patients were randomized, using the sequential parallel comparison design, into two 30-day phases, as follows: drug/drug (aripiprazole 2 mg/day in phase 1, aripiprazole 5 mg/day in phase 2), placebo/drug (placebo in phase 1, aripiprazole 2 mg/day in phase 2), or placebo/placebo (placebo in both phases). We examined changes in the KSQ score from baseline to endpoint on the basis of the subscaled Well-being and Reversal Distressed Anxiety Subscales. The score for the KSQ depression subscale improved from baseline to the end of follow-up, with a significant advantage for aripiprazole over placebo (P=0.0327). Although improvement was also observed in the anxiety and hostility scales, neither attained a significant advantage over placebo; no significant change was observed for the somatization subscale. Aripiprazole augmentation resulted in a significant improvement compared with placebo augmentation only in the depression subscale of the KSQ; however, the low dose may not have been enough to have an impact on the anxiety and hostility scales. The good tolerability of the low dose may have resulted in the absence of worsening of somatic symptoms. Prospective studies are needed to better characterize the impact of low doses of aripiprazole augmentation on different manifestations of MDD.

COGNITIVE IMPAIRMENT FOLLOWING CHILDHOOD EXPOSURE TO MODERATE DOSES OF IONIZING RADIATION

Background and Aims:Exposure to high doses of ionizing radiation results in a spectrum of cognitive deficits but the impact of lower doses is much less clear. The aim of this study was to investigate the effect of childhood exposure of the head to a mean dose of 1.5 Gy on reported memory problems and attention deficit after about 50 years. Methods:The study population included a subsample of individuals derived from the tinea capitis cohort, of which 253 irradiated and 162 non-irradiated subjects were interviewed (compliance rate 79.1% and 48.2% respectively, among those who could be located). Subjects completed a questionnaire covering socio-demographic and health topics. A section concerning memory problems and attention deficit (including details on symptoms, severity, and treatments) was incorporated using closed and free-text fields. To assess the effect of radiation on cognitive problems, multivariate Poisson regression models were performed. Results:About half of the study population was females and most individuals (73%) were aged between 55-64 years at interview. The mean age at irradiation was 7.4 years (range 1-15) and the average follow-up period was 52 years (range 44-63). More irradiated subjects than non-irradiated subjects reported memory problems (55.7% vs 35.8%, p&lt;.001) and attention deficit (33.2% vs. 14.8%, p&lt;.001). Controlling for age, gender, and SES level, irradiated subjects had a higher risk of having moderate-high severe memory problems (RR=2.00, 95%CI: 1.19-3.26) and moderate-high severe attention deficit (RR=3.48, 95%CI: 1.77-6.85) compared to the non-irradiated. Female gender and low SES level were found to be independent risk factors for memory problems. Conclusions:This study suggests that cognitive impairment may be a health outcome of exposure to moderate ionizing radiation in childhood. The long term effects of this exposure continue to be a public health concern considering the growing use of diagnostic modalities involving this exposure (primarily CT).

The focus of pathological (toxic) action of metals in the human body and the role of galvanic currents in its formation

Chronic influence of metals on the human body differs from their acute toxic effect. In some individuals subjected to a long-term chronic impact of low doses of metals, chronic inflammatory diseases, including oncological diseases, develop against a background of neurological symptoms. Today, the overwhelming majority of the population older than 40–50 years carry metal alloys in the form of dental prostheses and various implants in the body. Because of metal corrosion, an increased concentration of ions is formed in the body of these subjects. Galvanic currents induced in the presence of any metals promote corrosion and the transfer of metal ions in the body. If these currents are sufficiently strong (when the potential difference is more than 150 mV), the development of local inflammatory pathologies due to the concentration of metal ions in their foci is stimulated.

Endokrin aktive Substanzen in der Umwelt (Endocrine Disruptors): Gefahr für den Menschen?

Many substances from the technical and natural environment can cause damage to the endocrine system. Animal tests show that so-called endocrine disruptors (ED), such as pesticides, fungicides, plasticizers (phthalates), bisphenol A (BPA), and organotin compounds can interfere with the endocrine system. In humans, it is difficult to attribute such changes to specific ED. Nevertheless, in vitro studies with human cells and tissues clearly show that ED are able to interfere with endogenous hormones, i. e. affecting the steroid hormone metabolism and intracellular signaling. Several clinical studies show that humans are also affected, including reproductive disorders like reduction of spermatogenesis, decreased testosterone production or malformation of the genitals or induction of tumors like mammary carcinoma. Facing the body of reports documenting the effects of ED, the European Union supported--inter alia--COMPRENDO, a project addressing risk assessment of particular ED in human and wildlife species, while the FDA supports the industry's actions to stop producing BPA-containing baby bottles and infant feeding cups. Some ED show an u-shaped dose response curve and specific ED have effects at levels dramatically lower than thought relevant to traditional toxicology, a phenomenon termed "Low Dose Impact". Further research is needed to clarify whether the observed findings represent associations or causal results.

Effect of conjugated linoleic acid on bovine mammary cell growth, apoptosis and stearoyl Co-A desaturase gene expression

The effects of the primary biologically active conjugated linoleic acid (CLA) isomers ( cis-9, trans-11 and trans-10, cis-12; 15–150 μM) on growth and survival of the bovine mammary cell-line, Mac-T, were evaluated using cell enumeration and TUNEL assay. Previous studies have shown that high concentrations of CLA induced severe milk fat depression and have had negative effects on milk yield and composition whereas the impact of lower doses has been a modest depression in milk fat percent. In this study, we show that increasing concentrations of both CLA isomers had negative impacts on cell growth, including reduced cell number at concentrations of 35 μM and above ( P < 0.05) and a two-fold increase in induction of apoptosis in the mammary cells. Changes in cell morphology occurred with large vacuole-like structures in the cytoplasm, nuclear shrinkage and changes of nuclear shape to kidney shape. Insulin did not significantly affect apoptosis in CLA-treated cells. In addition, the effect of increased doses of CLA and the interaction of CLA and insulin on the bovine stearoyl Co-A desaturase ( Scd) gene promoter was also analyzed. While a significant difference in the Scd promoter transcriptional activity was not observed in cells treated with different concentrations of CLA, insulin significantly enhanced Scd promoter activity in CLA-treated cells. Our in vitro data support the hypothesis that high levels of CLA may induce in vivo apoptosis in the mammary gland.

Perspective: National Cancer Institute summary report about estimated exposures and thyroid doses received from iodine 131 in fallout after Nevada atmospheric nuclear bomb tests.

Environmental 131I contamination from atmospheric nuclear bomb tests conducted at the NTS from 1951 to 1958 exposed Americans nationwide to a cumulative average dose of 1 to 4 rad to the thyroid gland. By comparison, 10 years of exposure to natural background sources of thyroid radiation results in a cumulative dose of 1 rad. Americans living in certain high-deposition areas received an average cumulative thyroid dose of as much as 16 rad. Individual dose rates vary considerably as a function of age at the time of exposure, site of residence, and dietary habits with respect to milk consumption. The individual cumulative thyroid dose for persons born between 1945 and 1958 may be significantly higher than the reported averages for their locale. The NCI report contains voluminous data tables permitting detailed calculations of individual dose. Additionally, color-coded dose maps allow one to approximate individual dose conveniently. Translation of cumulative thyroid dose attributable to 131I to predictions of increased rates of thyroid cancer appears problematic and is the subject of further study. In contrast to studies of patients receiving external thyroid irradiation, existing studies of patients treated with 131I for diagnostic and therapeutic medical purposes do not document increased rates of thyroid cancer. An Institute of Medicine task force is expected to issue a report on this subject in September 1998. This review also briefly summarizes the evaluation, diagnosis, and treatment of patients with papillary and follicular thyroid cancers. Data from 53,856 patients with thyroid cancer accessioned to the NCDB from 1985 to 1995 document extremely high survival rates for patients in the United States with papillary and follicular thyroid cancer.