tbuckley/cabot-search huggingface dataset:
Bioequivalence of Generic and Brand-name Levothyroxine Products in the Treatment of Hypothyroidism
Authors: Betty J. Dong
Journal: JAMA (1997)

To compare relative bioavailability of Synthroid, Levoxine (Levoxine has been renamed Levoxyl), and 2 generic levothyroxine sodium preparations.Single-blind (primary investigators blinded), randomized, 4-way crossover trial.Ambulatory care.Twenty-two women with hypothyroidism who were clinically and chemically euthyroid and were receiving levothyroxine sodium, 0.1 or 0.15 mg.All patients received each of the 4 levothyroxine products for 6-week periods in the same dosage as their prestudy regimen with no washout period. The order of the drug sequences was randomly determined before study initiation.Area under the curve, time to peak serum concentrations, and peak serum concentrations of thyroxine, triiodothyronine, and free thyroxine index for all 4 products.All data analyses were completed prior to unblinding of the product codes. No significant differences between the 4 products were found in area under the curve or peak serum concentrations of total thyroxine, total triiodothyronine, or free thyroxine index. Although Synthroid produced a more rapid rise in total serum triiodothyronine concentration and a higher total peak serum triiodothyronine concentration than the other products, these differences were not statistically significant (P=.08). The Food and Drug Administration criterion for relative bioequivalence within 90% confidence intervals (0.8-1.25) was demonstrated (P<.05) for all pairs of products. Relative bioequivalence of 0.95 to 1.07 was demonstrated, tighter than the current bioequivalence criterion for oral formulations.The 4 generic and brand-name levothyroxine preparations studied are different but are bioequivalent by current Food and Drug Administration criteria and are interchangeable in the majority of patients receiving thyroxine replacement therapy. Further investigation is required to determine whether our results are equally applicable to all existing levothyroxine preparations.
Emotional distress in infertile women and failure of assisted reproductive technologies: meta-analysis of prospective psychosocial studies
Authors: J. Boivin, E. Griffiths, C. A. Venetis
Journal: BMJ (2011)

<b>1166</b> <h3><b>Objectives:</b></h3> In this educational exhibit, we present a 45-60 minute group learning exercise that aims to help learners become more confident in risk stratification, image interpretation, and radioactive iodine dose determination in regard to thyroid cancer. By the end of the group learning session, the resident/learner will be able to: Risk-stratify a specific patient9s disease using surgical pathology and a risk assessment system devised by the American Thyroid Association in 2015. Interpret the patient9s whole body scan images and incorporate this into clinical decision-making for radioactive iodine therapy. Present the patient9s case to the group, including recommendations for specific dose of radioactive iodine therapy. <h3><b>Methods:</b></h3> In this exhibit, materials and methods for the group learning exercise will be provided. This will include electronic handouts and short videos outlining risk stratification, whole body scan image interpretation, and radioactive iodine dose determination that can be viewed in 20 to 30 minutes by learners prior to the group learning exercise. Cases will be provided for groups of 3 to 4 residents, with individual learner roles within the group being specified so that the group can come up with a clinical presentation and recommendation regarding radioactive iodine therapy. Group facilitator instruction for leading the case-based group learning exercise will be provided. Materials and methods for the group learning exercise follow modern pedagogical practice. <h3><b>Results:</b></h3> &gt; After viewing this exhibit, educators will have a resource that can be utilized as is, modified as desired per individual institution requirements, or built upon for further resident education regarding nuclear medicine and thyroid disease. Conclusion: Group learning exercises can be valuable learning tools, particularly in medicine, where different levels of learners can help each other solve case-based problems as a team. We propose an easily implemented, short group learning exercise that may be useful in your academic practice.
The absence of a clathrin adapter confers unique polarity essential to proximal tubule function
Authors: Ryan Schreiner, Gustavo Frindt, Fernando Diaz, Jose M. Carvajal-Gonzalez, Andrés E. Perez Bay, Lawrence G. Palmer, Vladimir Marshansky, Dennis Brown, Nancy J. Philp, Enrique Rodriguez-Boulan
Journal: Kidney International (2010)
High-Frequency Components in the Electrocardiogram
Authors: ERNEST W. REYNOLDS, BERNARD F. MULLER, GARY J. ANDERSON, BRUCE T. MULLER
Journal: Circulation (1967)

Expanding the frequency response of the electrocardiogram and its derivative to 1,000 cps revealed notching in certain parts of the QRS complex which correlates with the presence of primary myocardial disease. Chi-square analysis of data from 169 patients with myocardial involvement indicated that notching on the downstroke of leads X, V 4 , and V 6 separated abnormal from normal patients at the 1% level of significance, whereas fine and coarse slurring showed reverse correlation at the 1% level of significance. This suggests that notching and not slurring is the important evidence of disease. Neither notching nor slurring was significant at the peak of the R wave in any lead. Study of individual cases revealed that complete right and left bundle-branch blocks do not mask high-frequency components caused by myocardial disease nor do they produce high-frequency components. Conclusions regarding specific diagnostic nostic criteria, however, should serve only as guidelines.
MORPHINE HYPERGLYCEMIA IN DOGS WITH EXPERIMENTAL PANCREATIC DEFICIENCY
Authors: John Auer, Israel S. Kleiner
Journal: The Journal of Experimental Medicine (1918)

The subcutaneous injection of 1 or 2 mg. of morphine sulfate per kilo subcutaneously in dogs with a pancreatic deficiency, whose sugar tolerance is still good, produces a rise in the glycemia about four times greater than the same amount of morphine calls forth in normal dogs. As dogs with a pancreatic deficiency due to coagulation or partial resection of the gland may legitimately be considered in a prediabetic state, the inference is warranted that the morphine test may be of value in detecting a weakened carbohydrate metabolism in the human subject. The test could easily and without danger be carried out with the micro methods now available for the quantitative determination of blood sugar. The experimental facts described in this paper give additional corroboration to the view that the response of a normal and of a pathologically altered organism to the same drug in the same dosage may be quantitatively very different.
Rapid Shortening During Relaxation Increases Activation and Improves Systolic Performance
Authors: Matthew W. Watkins, Akihiro Higashiyama, Zengyi Chen, Martin M. LeWinter
Journal: Circulation (1996)

Background Previous studies in cardiac muscle and isolated heart preparations generally have attributed positive effects of ejection to greater length-dependent activation. However, there have been some reports of an ejection-related increase in contractile function that is independent of end-diastolic volume (EDV) history. The present study was designed to more fully characterize the mechanoenergetic results of the latter effect in the intact ventricle. Methods and Results A servomotor was used to initiate left ventricular volume reduction (VR) at end systole, with EDV kept constant. Seven isolated, red blood cell-perfused rabbit hearts were studied at constant EDV during isovolumic contraction, slow VR (5.0±0.9 EDV/s), and rapid VR (26.8±5.1 EDV/s). Compared with isovolumic beats, VR caused an enhancement in contractility. This effect was greater for rapid VR and required &gt;50 beats to attain steady state. Rapid VR increased developed pressure by 15% (92.2±23.7 [mean±SD] versus 105.9±27.6 mm Hg), maximum dP/dt by 17% (1223±401 versus 1435±505 mm Hg·s − 1 ), and E max (slope of the end-systolic pressure-volume relation) by 13% (69.4±19.9 versus 78.6±23.0 mm Hg/mL) (all P &lt;.01). Left ventricular oxygen consumption (V̇ o 2 ) was unchanged with slow VR and decreased by 8% with rapid VR (0.0744±0.0194 versus 0.0683±0.0141 mL O 2 ·beat − 1 ·100 g − 1 ; P &lt;.05). In separate hearts (n=8), costs (basal metabolism and excitation-contraction coupling) were estimated by use of 2,3-butanedione monoxime. Compared with control, rapid VR was associated with a 26% increase in nonmechanical V̇ o 2 (0.0248±0.0021 versus 0.0312±0.0022 mL O 2 ·beat − 1 ·100 g − 1 ; P &lt;.01), consistent with an increase in calcium cycled per beat. Conclusions Ejection after end systole has a positive effect on ventricular performance that cannot be ascribed to length-dependent activation and is likely related to an increase in calcium available for activation. Similarly, an increase in nonmechanical V̇ o 2 associated with ejection suggests a positive interaction between myofilament shortening and activator calcium cycling.
Origin of the Term Internal Medicine
Authors: William B. Bean
Journal: New England Journal of Medicine (1982)

The names of various medical specialties are surprising. Some refer to districts of the body (ophthalmology and dermatology), some to techniques (roentgenology and surgery), some to age (geriatrics and pediatrics), and some to territorial imperatives (preventive medicine and industrial hygiene). Whether family practice is a discipline with its own unique corpus of scholarly knowledge is being debated. It is curious that the names of some specialties have come to signify what a specialist does, as in the expression "the patient had surgery today." We don't say that the patient had pediatrics or psychiatry, and though it would make sense of . . .
Tumor–specific autologous cytotoxic T lymphocytes from tissue sections
Authors: Shu Qin Liu, Hiroshi Shiraiwa, Koji Kawai, Hitoshi Hayashi, Hideyuki Akaza, Berm Soo Kim, Akinori Oki, Masato Nishida, Takeshi Kubo, Kazuko Hashizaki, Kaoru Saijo, Tadao Ohno
Journal: Nature Medicine (1996)
Spectrum and Outcome of Primary Cardiomyopathies Diagnosed During Fetal Life
Authors: Roland Weber, Paul Kantor, David Chitayat, Mark K. Friedberg, Fraser Golding, Luc Mertens, Lynne E. Nield, Greg Ryan, Mike Seed, Shi-Joon Yoo, Cedric Manlhiot, Edgar Jaeggi
Journal: JACC Heart Failure (2014)

The purpose of this study was to determine the phenotypic presentation, causes, and outcome of fetal cardiomyopathy (CM) and to identify early predictors of outcome.Although prenatal diagnosis is possible, there is a paucity of information about fetal CM.This was a retrospective review of 61 consecutive fetal cases with a diagnosis of CM at a single center between 2000 and 2012.Nonhypertrophic CM (NHCM) was diagnosed in 40 and hypertrophic CM (HCM) in 21 fetuses at 24.7 ± 5.7 gestational weeks. Etiologies included familial (13%), inflammatory (15%), and genetic-metabolic (28%) disorders, whereas 44% were idiopathic. The pregnancy was terminated in 13 of 61 cases (21%). Transplantation-free survival from diagnosis to 1 month and 1 year of life for actively managed patients was better in those with NHCM (n = 31; 58% and 58%, respectively) compared with those with HCM (n = 17; 35% and 18%, respectively; hazard ratio [HR]: 0.44; 95% confidence interval [CI]: 0.12 to 0.72; p = 0.007). Baseline echocardiographic variables associated with mortality in actively managed patients included ventricular septal thickness (HR: 1.21 per z-score increment; 95% CI: 1.07 to 1.36; p = 0.002), cardiothoracic area ratio (HR: 1.06 per percent increment; 95% CI: 1.02 to 1.10; p = 0.006), ≥3 abnormal diastolic Doppler flow indexes (HR: 1.44; 95% CI: 1.07 to 1.95; p = 0.02), gestational age at CM diagnosis (HR: 0.91 per week increment; 95% CI: 0.83 to 0.99; p = 0.03), and, for fetuses in sinus rhythm, a lower cardiovascular profile score (HR: 1.45 per point decrease; 95% CI: 1.16 to 1.79; p = 0.001).Fetal CM originates from a broad spectrum of etiologies and is associated with substantial mortality. Early echocardiographic findings appear useful in predicting adverse perinatal outcomes.
Scalp Ringworm in Scotland, 1946-7
Authors: J. Kinnear, J. Rogers
Journal: BMJ (1948)

The main object of this paper is to present a picture of ringworm of the scalp in the Eastern Region of Scotland (counties of Angus and Perth) from July 1, 1946, to the end of 1947.During this period there were two epidemics of small-spore ringworm and 631 cases were seen.Owing mostly to lack of appreciation of the factors involved, mis- leading or doubtful statements are still being made about ringworm of the scalp, and the opportunity is here taken to make categorical statements when these appear justified.Some experiments with local treatment are described.The great majority of cases of ringworm of the scalp in this country are due to microsporon infection, but as one travels south through Europe the proportion changes till in Italy nearly all cases are due to the trichophyton (Walker and Percival, 1939).Recent reports confirm this state- ment.Keddie (1947) found in an epidemic of scalp ring- worm in Bathgate, Scotland, that all the 351 children were infected by microsporon.Chmel (1946), in analysing results of cultures from 156 cases of ringworm, not confined to scalp cases, in Czechoslovakia from 1942 to 1946, found that microsporon was responsible for 40% (he states that the number is still increasing), Trichophyton endothrix 22.4%, T. ectothrix 26.9%, achorion 2.56%, and epidermophyton 8.14%.Catanei (1947) states that out of 871 cases of ring- worm in school-children in Algiers examined in 20 years 4.5% were due to microsporon (M.canis more often than M. audouini), 9.5% were favus, and the remaining 86% T. endothrix infections.In the U.S.A., reports of several epidemics have recently been published showing an overwhelming preponderance of microsporon infection of the scalp.Schwartz et al. (1946) found M. audouini in all but 8 cases out of 565 in Havers- town, Maryland, during 1944-5.Lewis et al. (1946) saw in the New York Hospital 312 patients with tinea capitis from July 1, 1943, to June 30, 1945 ; 305 were microsporon infec- tions (M.audouini 275, M. lanosum 30), 5 were due to T. endothrix, and 2 to achorion.Over 28 months to May, 1945, out of 928 cases in the Vanderbilt Clinic Miller et al. (1946) found 96.9% due to M. audouini, 2.6% due to M. felineum (M.lanosum), and only 0.5% due to other organisms.With regard to the type of microsporon found in this country, Duncan (1945) states that M. audouini seems to be the predominant species causing tinea capitis in the Midlands and North, while the animal types were common in school-children in the southern counties and in the London area.In the latter area the two types of micro- sporon were found in approximately equal numbers.Favus was formerly common in Scotland.McCall Anderson (1871) found it in 1.56% of 10,000 consecutive dispensary cases in Glasgow.Norman Walker (1899) stated that the opportunities of studying favus were numerous.in Scotland.As will be seen, it is now rare in the part of Scotland under consideration, though cases continue to crop up occasionally.Two Epidemics of Ringworm
Medial frontal cortex: from self-generated action to reflection on one's own performance
Authors: Richard E. Passingham, Sara L. Bengtsson, Hakwan C. Lau
Journal: Trends in Cognitive Sciences (2009)

It was suggested over 20 years ago that the supplementary motor cortex is involved in self-generated behaviour. Since then, there have been many studies using electrophysiology and brain imaging of the role of the supplementary motor cortex and anterior cingulate cortex. In light of the findings, the proposal that these regions are crucial for self-generated action has recently been challenged. Here, we review the recent literature and argue that the proposal survives the findings. We further argue that it can be generalised to cover reflection on mental states. Finally, we suggest that the pattern of anatomical connections is consistent with the proposal that the medial frontal cortex is crucially involved in self-generated action and self-reflection.
Osteoclasts expressing the measles virus nucleocapsid gene display a pagetic phenotype
Authors: Noriyoshi Kurihara, Sakamuri V. Reddy, Cheikh Menaa, Dirk Anderson, G. David Roodman
Journal: Journal of Clinical Investigation (2000)

Osteoclasts (OCLs) in Paget's disease are markedly increased in number and size, have increased numbers of nuclei per multinucleated cell, and demonstrate increased resorption capacity and increased sensitivity to 1,25-(OH)2D3, the active form of vitamin D. These cells also contain nuclear inclusions, reminiscent of those seen in paramyxovirus-infected cells, which cross-react with antibodies to measles virus nucleocapsid (MVNP) antigen. To elucidate the role of MV in the abnormal OCL phenotype of Paget's disease, we transduced normal OCL precursors with retroviral vectors expressing MVNP and the MV matrix (MVM) genes. The transduced cells were then cultured with 1,25-(OH)2D3 for14 or 21 days to induce formation of OCL-like multinucleated cells. The MVNP-transduced cells formed increased numbers of multinucleated cells, which contained many more nuclei and had increased resorption capacity compared with multinucleated cells derived from empty vector–transduced (EV-transduced) and MVM-transduced or normal bone marrow cells. Furthermore, MVNP-transduced cells showed increased sensitivity to 1,25-(OH)2D3, and formed OCLs at concentrations of 1,25-(OH)2D3 that were 1 log lower than that required for normal, EV-transduced, or MVM-transduced cells. These results demonstrate that expression of the MVNP gene in normal OCL precursors stimulates OCL formation and induces OCLs that express a phenotype similar to that of pagetic OCLs. These results support a potential pathophysiologic role for MV infection in the abnormal OCL activity and morphology that are characteristic of pagetic OCLs.
One gene, two transcripts: isolation of an alternative transcript encoding for the autoantigen La/SS-B from a cDNA library of a patient with primary Sjögrens' syndrome.
Authors: H Tröster, T E Metzger, I Semsei, M Schwemmle, A Winterpacht, B Zabel, M Bachmann
Journal: The Journal of Experimental Medicine (1994)

A cDNA library was prepared from peripheral blood lymphocytes of an autoimmune patient with primary Sjögrens' syndrome. The cDNA library was screened with the patients own autoimmune serum being monospecific for the nuclear autoantigen La/SS-B. Thereby an alternative type of La mRNA was identified that differed from the known La mRNA due to an exchange of the exon 1. Sequencing of the genomic region between the exons 1 and 2 showed that the alternative 5'-end is a part of the intron. In addition, the presence of an alternative promoter site, which exists within the intron downstream of the exon 1, became evident. In consequence, the alternative La mRNA is the result of a promoter switching combined with an alternative splicing mechanism. In the intron, further transcription factor binding sites, including a NF-kappa B element, were identified leading to the suggestion that the expression of the gene encoding for the nuclear autoantigen La/SS-B alters in dependence on disease conditions.
Temporal sequence of hard and soft tissue healing around titanium dental implants
Authors: Giovanni E. Salvi, Dieter D. Bosshardt, Niklaus P. Lang, Ingemar Abrahamsson, Tord Berglundh, Jan Lindhe, Saso Ivanovski, Nikos Donos
Journal: Periodontology 2000 (2015)

The objective of the present review was to summarize the evidence available on the temporal sequence of hard and soft tissue healing around titanium dental implants in animal models and in humans. A search was undertaken to find animal and human studies reporting on the temporal dynamics of hard and soft tissue integration of titanium dental implants. Moreover, the influence of implant surface roughness and chemistry on the molecular mechanisms associated with osseointegration was also investigated. The findings indicated that the integration of titanium dental implants into hard and soft tissue represents the result of a complex cascade of biological events initiated by the surgical intervention. Implant placement into alveolar bone induces a cascade of healing events starting with clot formation and continuing with the maturation of bone in contact with the implant surface. From a genetic point of view, osseointegration is associated with a decrease in inflammation and an increase in osteogenesis-, angiogenesis- and neurogenesis-associated gene expression during the early stages of wound healing. The attachment and maturation of the soft tissue complex (i.e. epithelium and connective tissue) to implants becomes established 6-8 weeks following surgery. Based on the findings of the present review it can be concluded that improved understanding of the mechanisms associated with osseointegration will provide leads and targets for strategies aimed at enhancing the clinical performance of titanium dental implants.
Abstract 423: SENP1 regulates OCT4 under hypoxia: effect of its sumoylation on protein stability and drug susceptibility of human pluripotent germ cell tumors
Authors: Yen-Hua Huang, Yu-Chih Wu, Thai-Yen Ling, Chia-Ning Shen
Journal: Cancer Research (2012)

Abstract Well-differentiated testicular germ cell tumors (TGCTs) are more drug insensitive and have a poorer prognosis than pluripotent germ cell tumors. However, the mechanism underlying the differentiation regulation of pluripotent seminomas/embryonal carcinomas (ECs) still remains largely unknown. Herein, we demonstrated an important role of SUMO1/sentrin specific peptidase 1 (SENP1) in the sumoylation and stability of the OCT4 protein in the drug sensitivity of hypoxic ECs. Hypoxia decreased the OCT4 protein level, but not the messenger RNA level, in pluripotent ECs. Hypoxic challenge and SUMO1 overexpression increased OCT4 sumoylation and protein instability. A further mutation at the specific OCT4 lysine 123 (HA-OCT4-K123R) effectively suppressed OCT4 sumoylation and protein instability, demonstrating the important role of the specific sumoylation of lysine 123 in OCT4 protein stability under hypoxia. Consistently, overexpression of SUMO1 decreased the endogenous OCT4 half-life in hypoxic NCCIT cells. The band-shift of endogenous sumoylated OCT4 in hypoxic NCCIT cells was demonstrated using Western blot analysis. SENP1 effectively suppressed OCT4 sumoylation and increased OCT4 stability and drug sensitivity in hypoxic NCCIT cells in vitro. Furthermore, overexpression of SENP1 in hypoxic NCCIT cells increased the drug sensitivity in a nude mice model, demonstrating the upstream regulation of SENP1 in OCT4 sumoylation, protein stability, and the drug susceptibility of NCCIT cells. In summary, we demonstrated that the sumoylation regulator, SENP1, positively regulates OCT4 stability and drug sensitivity of pluripotent EC cells through sumoylation. Findings of this study provide insights into the regulation by sumoylation of pluripotent TGCTs differentiation, which has the potential for pharmacological development of effective therapeutic targeting. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 423. doi:1538-7445.AM2012-423