How frequently should a patient taking amiodarone be screened for thyroid dysfunction?

Amiodarone-induced thyroid dysfunction (AITD) is a common complication of amiodarone therapy and its prevalence varies according to iodine intake, subclinical thyroid disorders and the definition of AITD. There is no consensus about the frequency of screening for this condition. We evaluated 121 patients on chronic regular intake of amiodarone (mean intake = 248.5 ± 89 mg; duration of treatment = 5.3 ± 3.9 years, range = 0.57-17 years) and with stable baseline cardiac condition. Those with no AITD were followed up for a median period of 3.2 years (range: 0.6-6.7) and the incidence rate of AITD, defined by clinical and laboratorial findings as proposed by international guidelines, was obtained (62.8 per 1000 patients/year). We applied the Cox proportional hazard model to adjust for potential confounding factors and used sensitivity analysis to identify the best screening time for follow-up. We detected thyroid dysfunction in 59 (48.7%) of the 121 patients, amiodarone-induced hypothyroidism in 50 (41.3%) and hyperthyroidism in 9 (7.5%). Compared with patients without AITD, there was no difference regarding dosage or duration of therapy, heart rhythm disorder or baseline cardiac condition. During the follow-up of the 62 patients without AITD at baseline evaluation, 11 developed AITD (interquartile range, IR: 62.8 (95%CI: 31.3-112.3) cases per 1000 patients/year), 9 of them with hypothyroidism - IR: 11.4 (95%CI: 1.38-41.2), and 2 hyperthyroidism - IR: 51.3 (95%CI: 23.4-97.5). Age, gender, dose, and duration of treatment were not significant after adjustment. During the first 6 months of follow-up the incidence rate for AITD was 39.3 (9.2-61.9) cases per 1000 patients/year. These data show that AITD is quite common, and support the need for screening at 6-month intervals, unless clinical follow-up dictates otherwise or further information regarding the prognosis of untreated subclinical AITD is available.

IL-6 upregulation contributes to the reduction of miR-26a expression in hepatocellular carcinoma cells

A recent study showed that miR-26a is downregulated in hepatocellular carcinoma tissues and that this downregulation is an independent predictor of survival. Interestingly, the same study also reported that miR-26a downregulation causes a concomitant elevation of IL-6 expression. Because miR-26a expression was found to be transcriptionally downregulated by oncogene c-Myc in various cancers, and the expression of c-Myc was increased by IL-6 stimulation, we hypothesized that IL-6 contributes to reduction of miR-26a in hepatocellular carcinoma. Serum IL-6 was measured by ELISA and miR-26a was detected by qRT-PCR. The data of 30 patients with hepatocellular carcinoma who had undergone surgical tumor resection revealed that serum IL-6 could be considered to be a predictor of survival up to 5 years for hepatocellular carcinoma patients (log-rank test, P < 0.05). We observed that the serum IL-6 concentration was inversely correlated with miR-26a expression in cancerous tissues (Pearson correlation test, r = -0.651, P < 0.01). Furthermore, by in vitro experiments with HepG2 cells, we showed that IL-6 stimulation can lead to miR-26a suppression via c-Myc activation, whereas in normal hepatocyte LO2 cells incubation with IL-6 had no significant effect on miR-26a expression. Taken together, these results indicate that miR-26a reduction in hepatocellular carcinoma might be due to IL-6 upregulation.

Stress-related hormone norepinephrine induces interleukin-6 expression in GES-1 cells

In the current literature, there is evidence that psychological factors can affect the incidence and progression of some cancers. Interleukin 6 (IL-6) is known to be elevated in individuals experiencing chronic stress and is also involved in oncogenesis and cancer progression. However, the precise mechanism of IL-6 induction by the stress-related hormone norepinephrine (NE) is not clear, and, furthermore, there are no reports about the effect of NE on IL-6 expression in gastric epithelial cells. In this study, we examined the effect of NE on IL-6 expression in immortalized human gastric epithelial cells (GES-1 cells). Using real-time PCR and enzyme-linked immunoassay, we demonstrated that NE can induce IL-6 mRNA and protein expression in GES-1 cells. The induction is through the β-adrenergic receptor-cAMP-protein kinase A pathway and mainly at the transcriptional level. Progressive 5′-deletions and site-directed mutagenesis of the parental construct show that, although activating-protein-1 (AP-1), cAMP-responsive element binding protein (CREB), CCAAT-enhancer binding protein-β (C/EBP-β), and nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) binding sites are all required in the basal transcription of IL-6, only AP-1 and CREB binding sites in the IL-6 promoter are required in NE-induced IL-6 expression. The results suggest that chronic stress may increase IL-6 secretion of human gastric epithelial cells, at least in part, by the stress-associated hormone norepinephrine, and provides basic data on stress and gastric cancer progression.

Intensity and physiological responses to the 6-minute walk test in middle-aged and older adults: a comparison with cardiopulmonary exercise testing

The 6-minute walk test (6MWT) is a simple field test that is widely used in clinical settings to assess functional exercise capacity. However, studies with healthy subjects are scarce. We hypothesized that the 6MWT might be useful to assess exercise capacity in healthy subjects. The purpose of this study was to evaluate 6MWT intensity in middle-aged and older adults, as well as to develop a simple equation to predict oxygen uptake ( V ˙ O 2 ) from the 6-min walk distance (6MWD). Eighty-six participants, 40 men and 46 women, 40-74 years of age and with a mean body mass index of 28±6 kg/m2, performed the 6MWT according to American Thoracic Society guidelines. Physiological responses were evaluated during the 6MWT using a K4b2 Cosmed telemetry gas analyzer. On a different occasion, the subjects performed ramp protocol cardiopulmonary exercise testing (CPET) on a treadmill. Peak V ˙ O 2 in the 6MWT corresponded to 78±13% of the peak V ˙ O 2 during CPET, and the maximum heart rate corresponded to 80±23% of that obtained in CPET. Peak V ˙ O 2 in CPET was adequately predicted by the 6MWD by a linear regression equation: V ˙ O 2 mL·min-1·kg-1 = -2.863 + (0.0563×6MWDm) (R2=0.76). The 6MWT represents a moderate-to-high intensity activity in middle-aged and older adults and proved to be useful for predicting cardiorespiratory fitness in the present study. Our results suggest that the 6MWT may also be useful in asymptomatic individuals, and its use in walk-based conditioning programs should be encouraged.

Alternative chromatographic system for the quality control of lipophilic technetium-99m radiopharmaceuticals such as [99mTc(MIBI)6]+

Knowledge of the radiochemical purity of radiopharmaceuticals is mandatory and can be evaluated by several methods and techniques. Planar chromatography is the technique normally employed in nuclear medicine since it is simple, rapid and usually of low cost. There is no standard system for the chromatographic technique, but price, separation efficiency and short time for execution must be considered. We have studied an alternative system using common chromatographic stationary phase and alcohol or alcohol:chloroform mixtures as the mobile phase, using the lipophilic radiopharmaceutical [99mTc(MIBI)6]+ as a model. Whatman 1 modified phase paper and absolute ethanol, Whatman 1 paper and methanol:chloroform (25:75), Whatman 3MM paper and ethanol:chloroform (25:75), and the more expensive ITLC-SG and 1-propanol:chloroform (10:90) were suitable systems for the direct determination of radiochemical purity of [99mTc(MIBI)6]+ since impurities such as99mTc-reduced-hydrolyzed (RH),99mTcO4- and [99mTc(cysteine)2]-complex were completely separated from the radiopharmaceutical, which moved toward the front of chromatographic systems while impurities were retained at the origin. The time required for analysis was 4 to 15 min, which is appropriate for nuclear medicine routines.

A dose-response curve for biodosimetry from a 6 MV electron linear accelerator

Biological dosimetry (biodosimetry) is based on the investigation of radiation-induced biological effects (biomarkers), mainly dicentric chromosomes, in order to correlate them with radiation dose. To interpret the dicentric score in terms of absorbed dose, a calibration curve is needed. Each curve should be constructed with respect to basic physical parameters, such as the type of ionizing radiation characterized by low or high linear energy transfer (LET) and dose rate. This study was designed to obtain dose calibration curves by scoring of dicentric chromosomes in peripheral blood lymphocytes irradiated in vitro with a 6 MV electron linear accelerator (Mevatron M, Siemens, USA). Two software programs, CABAS (Chromosomal Aberration Calculation Software) and Dose Estimate, were used to generate the curve. The two software programs are discussed; the results obtained were compared with each other and with other published low LET radiation curves. Both software programs resulted in identical linear and quadratic terms for the curve presented here, which was in good agreement with published curves for similar radiation quality and dose rates.

The crystal and molecular structure of 18-Crown-6 HgC12 and 18-Crown-6 Cdc12

Hg(18-Crown-6)C12 and Cd(18-Crown-6)C12 are isostructura1, space group Cl~ Z = 2. For the mercury compound, a = 10.444(2) A° , b = 11. 468(1) A° , c = 7.754(1) A° , a = 90.06(1)°, B = 82.20(1)°, Y = 90.07(1)°, Dobs = 1.87, Dca1c = 1.93, V = 920.05 13, R = 4.66%. For the cadmium compound, 000 a = 10.374(1) A, b = 11.419(2) A, c = 7.729(1) A, a = 89.95(1)°, B = 81.86(2)°, Y = 89.99(1)°, Dobs = 1.61, Dcalc = 1.64, V = 906.4613, R = 3.95%. The mercury and cadmium ions exhibit hexagonal bipyramidal coordination, with the metal ion located on a centre of symmetry in the plane of the oxygen atoms. The main differences between the two structures are an increase in the metal-oxygen distance and a reduction in the metalchloride distance when the central ion changes from Cd2+ to Hg2+. These differences may be explained in terms of the differences in hardness or softness of the metal ions and the donor atoms.

Second Welland Canal - Book 1, Survey Map 6 - Through Grantham and Louth Townships

Survey map of the Second Welland Canal created by the Welland Canal Company showing the area between the Townships of Grantham and Louth. Identified structures associated with the Canal include the floating tow path. The surveyors' measurements and notes can be seen in red and black ink and pencil. Features of the First Welland Canal are noted in red ink and include the old towing path, and the original bed of the Twelve Mile Creek. Local area landmarks are also identified and include streets and roads (ex. New Road, 1st Concession Road, and an unnamed road in the top right corner), an unnamed bridge along New Road, J. Martindale's House, an Old Saw Mill, Richardsons Creek, Georges Point, and an oak tree at Georges Point. Properties and property owners of note are: Concession 2 Lot 23 and Concession 3 Lot 23 in the Grantham Township, Concession 2 Lots 1 and 2, and Concession 3 Lots 1 and 2 in the Louth Township, Peter Weaver, J. Martindale, and John Bonner. A property belonging to the Board of Works is outlined in red at Georges Point.

Second Welland Canal - Book 2, Survey Map 1 - Locks 5, 6 and 7 in Grantham

Survey map of the Second Welland Canal created by the Welland Canal Company showing the Grantham Township just southeast of the Town of St. Catharines. Identified structures associated with the Canal include Locks 5, 6, and 7, two Lock House Lots, Small Lock House, waste weir, and the towing path. The surveyors' measurements and notes can be seen in red and black ink and pencil. Local area landmarks are also identified and include roads (ex. Road to Thorold), Dicks Creek, R. Collier's Saw Mill, a gate yard, paper mill, grist mill, store house, and a barn. Properties and property owners of note are: Concession 7 Lots 13, 14, and 15, R. Collier, Orson Phelps, and a Mill Lot leased to Richard Collier.

Second Welland Canal - Book 2, Survey Map 6 - Locks 19, 20, 21 and 22 in Grantham

Survey map of the Second Welland Canal created by the Welland Canal Company showing south Merritton along the boundary between the Grantham and Thorold Townships. Identified structures associated with the Canal include Locks 19, 20, 21, and 22, Lock Tenders House, and the towing path. The surveyors' measurements and notes can be seen in red and black ink and pencil. Local area landmarks are also identified and include streets and roads (ex. Pine Street and Macadamized Road), J. Brown Cement Mill, W. B. Hendershot Saw Mill, W. Parnall Spoke and Sash Factory, W. Beatty Saw Mill, W. Beatty Tannery, a number of structures (possibly houses) belonging to: Mrs. Aikins, J. Battle, and E. Keefer, and a foundry, smithy, and machine shop (all of which possible belonged to J. Dobbie). Properties and property owners of note are: Concession 10 Lots 9 and 10, W. C. Loan Company, P.H. Ball, and J. Keefer. Two small properties belonging to W. B. Hendershot and W. Beatty exist and are outlined in red. A half acre property reserved for a lock lot exists and is outlined in blue. An additional property reserved for a quarry is also identified, but not outlined.

Second Welland Canal - Book 3, Survey Map 6 - Canal along Chippewa Creek in Thorold

Survey map of the Second Welland Canal created by the Welland Canal Company showing the canal along Chippewa Creek in Thorold Township. Identified structures and features associated with the Canal include the towing path, the back ditch, and the waterway itself. The surveyors' measurements and notes can be seen in red and black ink and pencil. Local area landmarks are also identified and include roads (ex. Road to Welland), Chippewa Creek, and a pond. Properties and property owners of note are: Lots 214, 215, 216 and 222, and Heaslip.

Letter from Lt.Col. Chewett to Ensign Kuck- 6 Sept 1814

Transcript (spelling and grammar retained): York 6th Sepber [September] 1814 Sir I will thank your for the Rolls and Returns of the Pickering Company due on the 1st instance that I may Make up mine to be returned to the Adjutant General – I have the honor to be Sir Your Most Obed [Obedient] W Chewett Lt Col 3rd Reg Yk [York] Militia

Letter - E.C. Schmon to Arthur A. Schmon, 6 February 1917

The letter reads:" The sixth of February. Artie dear, I am going to be a real good girl and not make you read a long letter, when your thoughts are so completely occupied with "war". Newark is also greatly excited. All arrangements for the mobilization of the militia forces have been made, and in case of any local uprisings, two hundred policemen are to be added to the force. Of course everyone is thinking the worst at present, but I cannot help but believe that in a few months, people will feel like kicking themselves, for having done an unnecessary amount of worrying. (Let us hope so). If nothing unforeseen occurs, I am going to take the "Congressional limited" to Washington, Wednesday the twenty first. Saw in the paper that the public ceremonies of inauguration are to be eliminated, or I would go down the following week. Don't think to steadily about the war. It's bad for the head. Affectionately, Lessie."

Letter - E.C. Schmon to Arthur A. Schmon, 6 August 1918

The letter mentions some men that may be returning the United States and some that have returned. This letter is labelled number 138.

Letter - E.C. Schmon to Arthur A. Schmon, 6 March 1919

Eleanore Celeste begins by discussing her birthday gifts she received from friends and family. There is talk that Arthur might soon be release from the army. She also mentions she is teaching higher grades and she finds it "very hard". The children of celebrities in Newark attend the school she is currently placed. The letter is labelled number 242.