tbuckley/cabot-search huggingface dataset:
Identifying critical windows of exposure for children's health.
Authors: S G Selevan, C A Kimmel, P Mendola
Journal: Environmental Health Perspectives (2000)

Several authors have considered the importance of exposure timing and how this affects the outcomes observed, but no one has systematically compiled preconceptional, prenatal, and postnatal developmental exposures and subsequent outcomes. Efforts were undertaken to examine the information available and to evaluate implications for risk assessment for several areas: a) respiratory and immune systems, b) reproductive system, c) nervous system, d) cardiovascular system, endocrine system, and general growth, and e) cancer. Major conclusions from a workshop on "Critical Windows of Exposure for Children's Health" included a) broad windows of sensitivity can be identified for many systems but detailed information is limited; b) cross-species comparisons of dose to target tissue and better data on the exposure-dose-outcome continuum are needed; c) increased interaction among scientific disciplines can further understanding by using laboratory animal results in designing epidemiological studies and human data to suggest specific laboratory studies on mechanisms and agent-target interactions; and d) thus far, only limited attention has been given to peripubertal/adolescent exposures, adult consequences of developmental exposures, and genome-environment interactions. More specific information on developmental windows will improve risk assessment by identifying the most sensitive window(s) for evaluation of dose-response relationships and exposure, evaluation of biological plausibility of research findings in humans, and comparison of data across species. In public health and risk management, information on critical windows may help identify especially susceptible subgroups for specific interventions.
GPs left in a quandary
Authors: I. Dickson
Journal: BMJ (2010)

The recent BHS statement leaves general practitioners (GPs) with a dilemma of what to do with patients who are currently taking low dose aspirin for the primary prevention of cardiovascular disease.1

Most will have hypertension or diabetes, or both. They will have started aspirin treatment when type 2 diabetes was considered to be a secondary preventable …
Inter-Relations between β-Adrenergic Receptors, Adenylate Cyclase and Calcium
Authors: Howard L. Bleich, Emily S. Boro, Michael L. Steer, Daphne Atlas, Alexander Levitzki
Journal: New England Journal of Medicine (1975)

THE catecholamines are a group of hormones that affect most tissues, not only in human beings, but in almost all animal phyla.1 Whether they are released locally by certain nerve endings or into the general circulation by the adrenal medulla, circulating catecholamines, such as epinephrine and norepinephrine, may regulate basic cellular processes like ion transport, enzyme secretion, glycogenolysis, lipolysis and muscle contraction.2 An understanding of their action is therefore needed for an understanding of a variety of cellular activities.In early studies, extracts of the adrenal medulla were injected into intact animals, and physiologic responses such as blood pressure were . . .
A CASE OF MALTA FEVER
Authors: Henry S. Acken
Journal: JAMA (1926)

R. G., a minister, aged 39, admitted to the service of Dr. Kandt, Nov. 30, 1925, complaining of headache over the eyes and soreness of the abdomen of five weeks duration, had been treated at his home in New York State during the previous five weeks. The family and past histories were negative. The illness really began about the first of September, 1925, when the patient began to have a feeling of persistent fatigue and weakness. November 4, he had his first known rise of temperature to 101. This dropped during the following week but rose again on the 9th to 102, when he had a chill and profuse sweat, together with persistent headache and abdominal soreness. A tentative diagnosis of typhoid was made by his family physician, but the Widal test was returned as negative. By November 16, the temperature had reached normal, but a week later the patient
ERGOT AND ARSENIC IN CHOREA
Authors: C. Riviere
Journal: BMJ (1905)

protuberance of the abdomen shown in the photograph, eats well and sleeps well, and is making great progress in his studies, in which, owing to his ill-health, he was very back--ward.In recorded cases of constipation the fortnightly evacuation is almost common, and longer periods not unknown, as instance a case recorded by Oliver in the BRITISH MEDICAL JOURNAL in I896 (vol.ii, p. 839), where there was complete closure of the bowels for two months, and an extreme one, quoted by Eustace Smith, of three months.This case owes its interest rather to the duration of the -condition of constipation, the enormous amount of the retained material-practically a third of the body weightand the satisfactory result of treatment.
Website of the week: AIDS: the global challenge
Authors: Tessa Richards
Journal: BMJ (2001)

With 23 million people dead and 36 million HIV positive, the need to do more to tackle AIDS is painfully clear. This week's BMJ (pp 1440, 1451, 1475) draws attention to the catastrophe. To get a comprehensive internet update on AIDS, the best website to visit is www.aegis.com. This is the largest HIV/AIDS site and it contains a vast amount of information, useful links, and an impressive news archive, which is updated hourly.

As we went to press it was heartening to be signposted to an article in the Washington Post suggesting that the new Global Health Fund to tackle AIDS, tuberculosis, and malaria is gathering momentum. France has joined the United States and United Kingdom in making a formal pledge ($127m; £89m). The first corporate donation ($1m) has just been made by a subsidiary of Credit Suisse. The sums are paltry compared with the $10bn target, but these donations may spur other governments and private institutions to follow suit at the United Nations General Assembly session on HIV/AIDS next week.

At this meeting, recent data will be aired showing that the HIV/AIDS epidemic is worsening, not only in Africa but also in parts of Asia and Latin America. Most of those affected live in Africa and although www.safaids.org and www.gnpplus.net are African AIDS sites, neither approaches the quality or topicality of www.thebody.com—a global network that aims to improve the quality of life of people with HIV/AIDS. Comprehensive news updates and useful links complement a wealth of practical information.

Jumping off to www.avert.org/news.htm reminded me that, despite the pledge to donate 0.7% of GNP to development assistance, the UK still donates only 0.31%. Most Scandinavian countries do much better. By contrast, the US is bottom of the list, contributing a miserly 0.1%.
Efficacité et morbidité de la mucosectomie endoscopique du tube digestif: résultats du registre prospectif national
Authors: D Heresbach
Journal: Endoscopy (2008)

Introduction: Le traitement des dysplasies ou des cancers précoces du tube digestif repose sur leur exérèse endoscopique notamment par mucosectomie (EMR). Les résultats du traitement par EMR reposent sur des séries le plus souvent rétrospectives et monocentriques de centres sélectionnés et référents. L'objectif de notre registre est d'enregistrer de façon prospective et consécutive les modalités et résultats des mucosectomies endoscopiques réalisées en France pendant 1 an en hôpital privé ou public.
Bone marrow transplantation in a young child with sickle cell anemia
Authors: Karen A. Kalinyak, Christopher Morris, William S. Ball, M. Douglas Ris, Richard Harris, Donald Rucknagel
Journal: American Journal of Hematology (1995)

Abstract Bone marrow transplantation (BMT) is the only curative therapy available for hemoglobinopathies. BMT was performed on a young child with sickle cell anemia (SCA) after approximately 9 months of transfuslon therapy following her initial stroke. The patient received a matched sibling donor (sickle trait) BMT. The conditioning regimen consisted of busulfan 4 mg/kg/day × 4, cyclophosphamide 50 mg/kg/day × 4. Graft vs. host disease prophylaxis was daily cyclosporine for 6 months. There were no significant complications during BMT. Engraftment occurred on day + 17 and the patient was transfusion independent since day +45. Pre‐BMT cerebral arteriography showed multiple stenotic cerebral vessels and a moya‐moya pattern. Perfusion MRI demonstrated reduced capillary perfusion. Approximately 170 days after BMT the patient experienced episodes of transient left‐sided weakness and speech problems. Neuroimaging revealed progression of large vessel pathology by angiography despite significant improvement in cortical perfusion (MR perfusion scan). Molecular analysis by PCR and DNA fingerprinting confirmed absence of mixed mosaicism. Rheologic evaluation showed normal corrected bulk viscosity. It is possible that progression of large vessel pathology and return of clinical symptoms in the face of normal rheologic parameters may be due to worsening of the already damaged cerebral vessels by the BMT conditioning regimen. Further evaluations of patients with SCA undergoing BMT after a stroke are needed to answer this question. © 1995 Wiley‐Liss, Inc.
Conditional Survival After Radical Nephroureterectomy for Upper Tract Carcinoma
Authors: Guillaume Ploussard, Evanguelos Xylinas, Yair Lotan, Giacomo Novara, Vitaly Margulis, Morgan Rouprêt, Kazumasa Matsumoto, Pierre I. Karakiewicz, Francesco Montorsi, Mezut Remzi, Christian Seitz, Douglas S. Scherr, Anil Kapoor, Adrian S. Fairey, Ricardo Rendon, Jonathan Izawa, Peter C. Black, Louis Lacombe, Shahrokh F. Shariat, Wassim Kassouf
Journal: European Urology (2014)
Ketamine helps a third of patients with treatment resistant depression, finds small UK study
Authors: I. Torjesen
Journal: BMJ (2014)

A course of ketamine delivered intravenously could potentially be used to treat severe depression in patients who do not respond to other drugs, a UK study has found.

Currently electroconvulsive therapy may be offered to treatment resistant patients, but the potential benefits have to be balanced against the risk of memory loss.

Small randomised trials have shown that a single infusion of ketamine can have a substantial and rapid antidepressive effect in some treatment resistant patients who had been taken off other antidepressants.1 However, most of these patients relapsed within a week. Ketamine is a licensed drug that is widely used as an anaesthetic and in pain relief but is a class C banned substance because it is also used recreationally.

Researchers in Oxford decided to explore the safety and effectiveness …
Abstract 5177: Genome-wide profiling of somatic mutations in liver cancers revealed significantly mutated genes and non-coding regions in liver cancers
Authors: Mayuko Furuta, Akihiro Fuimoto, Yuichi Shiraishi, Satoru Miyano, Tatsuhiko Tsunoda, Hidewaki Nakagawa
Journal: Cancer Research (2014)

Abstract Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide. Previously we have reported genomic aberrations detected by the whole genome sequencing (WGS) of 27 HCCs and frequently and recurrently mutated genes in this tumor (Nat Genet, 2012). Consistent with recent reports of WGS on human cancers from other groups, large parts of somatic point mutations (98.4%) were detected in non-coding genomic regions in our HCC samples. However, the consequence and significance of somatic mutations in non-coding regions are largely unknown. Here we analyzed 107 hepatitis C virus- (HCV-) associated HCCs by WGS analysis and calculated the somatic mutation rate of all single nucleotide variations (SNVs) and insertion-deletions (indels) within each 500-base bins on entire human genome. Among the whole genomic regions, 67 bins were significantly selected. After removing mutations in self-chained regions or simple repeat regions, which is expected to be false positives due to mapping errors, the bin containing exon 3 of CTNNB1 and multiple bins contains exons of TP53, which are known as driver mutations in HCCs, were highly ranked. In addition, entire coding region of the ALB gene showed high mutation rate compared with surrounding region distinctively. Interestingly, a recurrent short deletion on chromosome 18 was observed in the similar frequency as alterations of CTNNB1 or TP53. This short deletion was somatically detected in 35 of 321 liver cancers (10.9%) by Sanger sequencing. Significant accumulation of somatic mutations on exons of genes such as CTNNB1 and TP53 within entire genome through comparative analyses indicates their importance in hepatocarcinogenesis. Moreover, these results also suggest that novel mutations on non-coding regions, which are somatically and recurrently detected in higher rate in liver cancers, are involved in liver cancer development. These comprehensive approaches using WGS data will help the understanding of functions and alterations in non-coding regions occurred in cancer genome. Citation Format: Mayuko Furuta, Akihiro Fuimoto, Yuichi Shiraishi, Satoru Miyano, Tatsuhiko Tsunoda, Hidewaki Nakagawa. Genome-wide profiling of somatic mutations in liver cancers revealed significantly mutated genes and non-coding regions in liver cancers. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5177. doi:10.1158/1538-7445.AM2014-5177
The Usefulness of Chest Radiographs Obtained after a Demonstrated Perfusion Scan Defect in the Diagnosis of Pulmonary Emboli
Authors: VERNON A VIX
Journal: Clinical Nuclear Medicine (1983)

The chest radiographs obtained within seven days of scintigraphic lung studies in 38 patients clinically suspected of having a pulmonary embolus were reviewed. Twenty-two of these patients also had pulmonary angiograms. Lung densities in areas of perfusion defects not present at the time of the scan studies were sought. Densities were observed in ten patients. These appeared 4 hours to five days later (mean 1.8 days). This sequence of events strongly supports the diagnosis of pulmonary embolism. Chest radiographs are recommended one day and, if normal, again three days after an abnormal perfusion lung scan, even if the pulmonary angiogram is normal. The delayed appearance of these lung densities will eliminate some non-emboli causes and thereby strengthen the diagnosis of embolism. If such densities are seen following a "normal" angiogram, it should be critically reviewed.
JEADV: Journal of the European Academy of Dermatology and Venereology
Authors: Gary D. Byrd
Journal: JAMA (1994)

When the American Academy of Dermatology proposed publication of the<i>Journal of the American Academy of Dermatology</i>in 1979, many dermatologists expressed concern that a new journal would detract from both the<i>Archives of Dermatology</i>and the<i>Journal of Investigative Dermatology</i>. In fact, the two established journals and the new journal have all thrived. Apparently there was a source of articles for all three, and, in retrospect, it is clear that the new journal arose in response to a real need. This is not always the case. Commercial publishers are anxious to establish new journals, and these endeavors often struggle for initial acceptance and then suffer more or less ignominious deaths. Dermatology is growing in Europe and has a superb academic and clinical base there. The European Academy of Dermatology and Venereology provides a logical organizational and financial base with a large reserve of readers and authors, and it is
International Hepatology Communications
Authors: David H. Morse
Journal: JAMA (1994)

Given the prodigious output of research publication related to liver and liver disease, it is somewhat surprising that only a handful of journals devoted exclusively to hepatology have established themselves as standards. This in part explains the fact that of the approximately 15000 articles relating to liver and liver disease published in 1993 and indexed in MEDLINE, only about 1000 appeared in journals exclusively devoted to hepatology. The rest of the articles are widely diffused in journals of gastroenterology, pathology, cancer, immunology, virology, pharmacology, and experimental genetics. About 2000 of those liver-related articles in 1993 represented the work of Japanese investigators, regarded as world leaders in the area of hepatitis C and hepatocellular carcinoma research. In spite of a distinguished international editorial board, Elsevier's new entry into this field,<i>International Hepatology Communications</i>, contains almost exclusively Japanese research, with only four articles from outside Japan among the 32 published in the
Reduction in Wound Bioburden using a Silver‐Loaded Dissolvable Microfilm Construct
Authors: Maggie Herron, Ankit Agarwal, Patricia R. Kierski, Diego F. Calderon, Leandro B. C. Teixeira, Michael J. Schurr, Christopher J. Murphy, Charles J. Czuprynski, Jonathan F. McAnulty, Nicholas L. Abbott
Journal: Advanced Healthcare Materials (2014)

Silver is a widely used antimicrobial agent, yet, when impregnated in macroscopic dressings, it stains wounds, can lead to tissue toxicity, and can inhibit healing. Recently, polymeric nanofilms containing silver nanoparticles were reported to exhibit antimicrobial activity at loadings and release rates of silver that are 100× lower than conventional dressings. Here, fabrication of composite microfilm constructs that provide a facile way to transfer the silver‐loaded polymeric nanofilms onto wounds in vivo is reported. The construct is fabricated from a silver nanoparticle‐loaded polymeric nanofilm that is laminated with a micrometer‐thick‐soluble film of polyvinylalcohol (PVA). When placed on a moist wound, the PVA dissolves, leaving the silver‐loaded nanofilm immobilized on the wound‐bed. In vitro, the immobilized nanofilms release &lt;1 μg cm −2 d ‐1 of silver over 30 d from skin dermis and they kill 5 log 10 CFUs of Staphylococcus aureus in 24 h. In mice, wounds inoculated with 10 5 CFU S. aureus presented up to 3 log 10 less bacterial burden when treated with silver/nanofilms for 3 d, as compared to unmodified wounds. In uncontaminated wounds, silver/nanofilms allow normal and complete wound closure by re‐epithelialization. Dissolvable microfilm constructs may overcome key limitations associated with current uses of silver in wound healing.
Sequestered tracer outflow recovery in multiple indicator dilution experiments
Authors: Carl A. Goresky, Glen G. Bach, Allan W. Wolkoff, Colin P. Rose, Daniel Cousineau
Journal: Hepatology (1985)

The rapid, single injection, multiple indicator dilution technique has been, with suitable modeling of hepatic venous outflow curves, the standard approach for quantitative kinetic assessment of tracer cell entry and intracellular sequestration in the steady state, both in the in situ and the isolated perfused liver. Analysis of the underlying system yields, for a substance sequestered within liver cells, identical theoretical expressions for expected cumulative tracer fractional recovery and the steady-state fractional outflow recovery of the bulk substance whose behavior is being traced. Luxon and Forker (Am. J. Physiol. 1982; 243:G76–G89) pointed out that experimental cumulative tracer fractional recovery must match the value predicted by use of fitted model parameters in the theoretical recovery expression, and that this agreement must be regarded as the hallmark of successful fitting and modeling. Their attempts to demonstrate this agreement, by use of previously published data, were unsuccessful; this led them to question whether previous model analyses were valid. To reexamine the question we, therefore, analyzed three sets of data, on bilirubin, free fatty acid and galactose uptake, including those they had previously analyzed. We found excellent agreement between experimentally determined cumulative tracer recovery and theoretically predicted recovery. The theoretical recovery expression, now validated experimentally, provides a direct way of using fitted parameters for the rapid calculation of outflow recovery, which should prove generally useful in this area of kinetics. Demonstration of the expected agreement, moreover, restores confidence in the self-consistency of procedures used in the past to analyze multiple indicator dilution data.
Abstract 339: Inhibition of NANOG/NANOGP8 downregulates MCL-1 in colorectal cancer (CRC) cells, enhances the efficacy of BH3 mimetics and inhibits clonogenicity
Authors: Abid R. Mattoo, Jingyu Zhang, Luis A. Espinoza, Snorri S. Thorgeirsson, J. M. Jessup
Journal: Cancer Research (2014)

Abstract Combining lentiviral (LV) delivered shRNA against NANOG (shNG-1) or NANOGP8 (shNp8-1) with BH3 mimetics (ABT-737 and ABT-199) was undertaken to determine whether inhibition of NANOG/NANOGP8 enhances the cytotoxic effect of these BH3 mimetics in Colorectal Cancer (CRC) cells. NANOG is a key transcription factor important for both pluripotency in embryonic stem cells and malignant transformation and progression of colorectal carcinoma (CRC). Inhibition of NANOG or its paralog NANOGP8 reduces the proliferation, stemness and tumorigenicity of CRC cells. The cytotoxic potential of ABT-737 or ABT-199, as single agents, was tested in the CRC cell lines- Clone A, CX-1 and LS174T that have high levels of anti-apoptotic BCL-2 family proteins. Treatment with ABT-737 or ABT-199 showed variable cytotoxicity in the three CRC lines with LS174T being the most resistant. Inhibition of NANOG and NANOGP8 with LVshNG-1 or LVshNp8-1 in these cell lines decreased expression of MCL-1. The combination of LVshNG-1 and/or LVshNp8-1, with ABT-737 produced enhanced killing of the CRC cells by caspase-dependent apoptosis. These results were were confirmed when LV shNG-1 or LV shNp8-1 was used in combination with ABT-199. siRNA targeting MCL-1 reproduced the effects of NANOG/NANOGP8 inhibition. The CRC cells that survived the combination treatment showed lower regrowth potential and reduced clonogenicity when re-plated in fresh media. These results demonstrate that inhibition of NANOGP8 or NANOG enhances the cytotoxicity of BH3 mimetics that target BCL-2 family members through inhibition of MCL-1 expression. Citation Format: Abid R. Mattoo, Jingyu Zhang, Luis A. Espinoza, Snorri S. Thorgeirsson, J. M. Jessup. Inhibition of NANOG/NANOGP8 downregulates MCL-1 in colorectal cancer (CRC) cells, enhances the efficacy of BH3 mimetics and inhibits clonogenicity. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 339. doi:10.1158/1538-7445.AM2014-339
Yet another way to contract giardiasis?
Authors: Phil Gunby
Journal: JAMA (1982)

When Stanley H. Schuman, MD, DPH, took a day off to accompany his son to see an orthopedic surgeon for treatment of a football shoulder injury, it became the epidemiologist's equivalent of a busman's holiday.  Schuman, who is professor of epidemiology in the Department of Family Medicine at the Medical University of South Carolina, Charleston, became fascinated when the orthopedic surgeon mentioned a harrowing bout of gastroenteritis. The surgeon, a well-built six-footer, had lost 15% of his body weight over approximately a month and had suffered from epigastric pain, cramps, bloating, diarrhea, and anorexia.  A colleague suspected giardiasis, which was confirmed by stool examination, and the surgeon recovered after ten days' treatment with metronidazole. But the question remained: How had he contracted the giardial infection in the first place?  This opportunity to do some medical detective work intrigued Schuman, and the result is what apparently is the first report of