tbuckley/cabot-search huggingface dataset:
Creating the right environment
Authors: Ruth Williams
Journal: The Journal of Experimental Medicine (2006)

![Graphic][1] 

Normal development of the bone marrow HSC niche (left) fails in the absence of Bmi1 (right). Like baby chicks, stem cells need a nest—a niche within the body where they reside and self-renew. Oguro et al. (page 

[2247][2]) find that, for blood stem cells, this nest is
Comparison of features by MRI and radiographs of the interphalangeal finger joints in patients with hand osteoarthritis
Authors: Ida K Haugen, Pernille Bøyesen, Barbara Slatkowsky-Christensen, Sølve Sesseng, Jessica Bijsterbosch, Désirée van der Heijde, Tore K Kvien
Journal: Annals of the Rheumatic Diseases (2011)

Objectives To examine the construct validity of MRI in the detection of structural hand osteoarthritis features with conventional radiography (CR) as reference and explore the association between radiographic severity and MRI-defined pathology. Methods 106 hand osteoarthritis patients (97 women, mean age 68.9 years (SD 5.6)) had 1.0T contrast-enhanced MRI and CR of the dominant hand. The 2nd–5th interphalangeal joints were scored according to the preliminary Oslo hand osteoarthritis MRI score and Kellgren–Lawrence (KL) scale and Osteoarthritis Research Society International atlas for radiographs. The authors compared the number of joints with structural features by MRI and CR (Wilcoxon signed-rank test) and examined concordance at the individual joint level. The OR of MRI features in joints with doubtful (KL grade 1), mild (2) and moderate/severe (≥3) radiographic osteoarthritis was estimated by generalised estimating equations (KL grade 0 as reference). Results MRI detected approximately twice as many joints with erosions and osteophytes compared with CR (p&lt;0.001), but identification of joint space narrowing, cysts and malalignment was similar. The sensitivity of MRI was very high for osteophytes (1.00) and erosions (0.95), while specificity was lower (0.22 and 0.63). The prevalence of most MRI features increased with radiographic severity, but synovitis was more frequent in joints with mild osteoarthritis (OR2.1, 95% CI 1.4 to 3.2) than in moderate/severe osteoarthritis (OR1.4, 95% CI 1.0 to 2.2). Conclusion MRI detected more osteophytes and erosions than CR, suggesting that erosive osteoarthritis may be more common than indicated by CR. Synovitis was most common in mild osteoarthritis. Whether this is due to burn-out of inflammation in late disease must be investigated further.
Sustained release oral aminophylline in patients with airflow obstruction.
Authors: A P Greening, E Baillie, H R Gribbin, N B Pride
Journal: Thorax (1981)

Twenty-four patients with reversible airflow obstruction under suboptimal control on conventional therapy entered a double-blind placebo-controlled trial of additional oral sustained release aminophylline. Assessment was by diary cards, twice daily PEFR, and weekly FEV1. Nineteen patients completed the trial satisfactorily. Eleven were improved subjectively by addition of aminophylline. The mean PEFR for all 19 patients rose from 232 1 min-1 SEM +/- 5, to 247 1 min-1 SEM +/- 4 (p less than 0.0001); nine individuals showed a statistically significant improvement in mean PEFR and 10 showed an improvement of greater than 200 ml in their FEV1. Improvement in PEFR on aminophylline was not at the expense of benefit from inhaled salbutamol. Unwanted effects of nausea, headache, and abdominal discomfort were recorded by 12 of the 24 patients entering the trial. Seventeen of the 19 patients completing the trial had plasma theophylline levels in the accepted therapeutic range of 10-20 mg 1(-1). The drug doses required to achieve these levels varied from 8.6-30.8 mg kg-1 24 hr-1 in the patients with no clinical or biochemical evidence of liver disease. Oral aminophylline can improve control of airflow obstruction in patients with moderately severe disease who are already receiving multiple medication, but side-effects often limit its use. The wide dose range required to achieve therapeutic plasma levels indicates that measurements of plasma theophylline are necessary for adequate interpretation of trials of theophylline compounds.
Perinatal Episodes Across the Mood Disorder Spectrum
Authors: Arianna Di Florio, Liz Forty, Katherine Gordon-Smith, Jess Heron, Lisa Jones, Nicholas Craddock, Ian Jones
Journal: JAMA Psychiatry (2012)

CONTEXT Affective disorders are common in women, with many episodes having an onset in pregnancy or during the postpartum period. OBJECTIVE To investigate the occurrence and timing of perinatal mood episodes in women with bipolar I disorder, bipolar II disorder, and recurrent major depression (RMD). SETTING AND PATIENTS Women were recruited in our ongoing research on the genetic and nongenetic determinants of major affective disorders. Participants were interviewed and case notes were reviewed. Best-estimate diagnoses were made according to DSM-IV criteria. The 1785 parous women identified included 1212 women with bipolar disorder (980 with type I and 232 with type II) and 573 with RMD. Data were available on 3017 live births. MAIN OUTCOME MEASURES We report the lifetime occurrence of perinatal mood episodes, the rates of perinatal episodes per pregnancy/postpartum period, and the timing of the onset of episodes in relation to delivery. RESULTS More than two-thirds of all diagnostic groups reported at least 1 lifetime episode of illness during pregnancy or the postpartum period. Women with bipolar I disorder reported an approximately 50% risk of a perinatal major affective episode per pregnancy/postpartum period. Risks were lower in women with RMD or bipolar II disorder, at approximately 40% per pregnancy/postpartum period. Mood episodes were significantly more common in the postpartum period in bipolar I disorder and RMD. Most perinatal episodes occurred within the first postpartum month, with mania or psychosis having an earlier onset than depression. CONCLUSIONS Although episodes of postpartum mood disorder are more common in bipolar I disorder and manic and psychotic presentations occur earlier in the postpartum period, perinatal episodes are highly prevalent across the mood disorder spectrum.
Longstanding atrial fibrillation causes depletion of atrial natriuretic peptide in patients with advanced congestive heart failure
Authors: Maarten P. van den Berg, Geert Tjeerdsma, Pieter Jan de Kam, Frans Boomsma, Harry J.G.M. Crijns, Dirk J. van Veldhuisen
Journal: European Journal of Heart Failure (2002)
Survival of breast cancer patients with meningeal carcinomatosis
Authors: H. Gauthier, M.N. Guilhaume, F.C. Bidard, J.Y. Pierga, V. Girre, P.H. Cottu, V. Laurence, A. Livartowski, L. Mignot, V. Diéras
Journal: Annals of Oncology (2010)
Double-blind Cross-over Trial Comparing Intranasal Beclomethasone Dipropionate and Placebo in Perennial Rhinitis
Authors: G. J. Gibson, D. J. Maberly, S. Lal, M. M. Ali, A. G. Butler
Journal: BMJ (1974)

Twenty-five patients with perennial rhinitis completed a double-blind cross-over trial of intranasal beclomethasone dipropionate 200 μg daily and placebo. Of these patients 19 preferred the active drug and two preferred placebo. There were significant reductions in symptom scores for nasal obstruction and rhinorrhoea and in the use of decongestant nasal drops when using the active drug. No changes in morning plasma cortisol levels occurred during the three-week treatment period.
The impact of activated p-AKT expression on clinical outcomes in diffuse large B-cell lymphoma: a clinicopathological study of 262 cases
Authors: J.Y. Hong, M.E. Hong, M.K. Choi, Y.S. Kim, W. Chang, C.H. Maeng, S. Park, S.J. Lee, I.-G. Do, J.-S. Jo, S.H. Jung, S.J. Kim, Y.H. Ko, W.S. Kim
Journal: Annals of Oncology (2013)
Trends in sales weighted tar, nicotine, and carbon monoxide yields of UK cigarettes
Authors: M J Jarvis
Journal: Thorax (2001)

Reducing tar yields of manufactured cigarettes has been an important plank of government policy on tobacco, but sale weighted yields are not routinely published.Tar, nicotine, and carbon monoxide yields measured by the Laboratory of the Government Chemist were combined with cigarette brand market shares from national surveys of smoking behaviour to generate sales weighted yield estimates for the period 1972-99.Sales weighted mean tar yields have declined steadily and in 1999 were 9.6 mg per cigarette, less than half their level in 1972. Over the same period nicotine yields have come down from 1.33 mg to 0.79 mg per cigarette. Carbon monoxide yields have shown smaller declines. At the same time as absolute yields have declined, there have also been changes in tar to nicotine ratios. Smokers in 1999 were exposed to 22% less tar per unit of nicotine than in 1973, and smokers of low tar brands have consistently been exposed to less tar per unit of nicotine than smokers of other brands.The value of reducing cigarette tar and nicotine yields has been questioned, since the tendency of smokers to compensate for reductions in nicotine delivery undermines the policy. The favourable trends in tar to nicotine ratios suggest that, despite this, there may have been some modest public health benefit. It cannot be assumed that future reductions from present levels would necessarily result in further improvement in tar to nicotine ratios. An explicit focus on the ratio of tar to nicotine may provide a metric of greater relevance for public health than the present emphasis on absolute tar yields.
Necropsy Studies in Myocardial Infarction with Minimal or No Coronary Luminal Reduction Due to Atherosclerosis
Authors: R. S. ELIOT, G. BAROLDI, A. LEONE
Journal: Circulation (1974)

A postmortem study was conducted on the hearts of 10 patients who died with a typical clinical picture of acute myocardial infarction within 25 days of onset of symptoms. The coronary arterial systems of the patients revealed minimal or no luminal reduction due to coronary atherosclerosis or other cause. These cases contribute to the understanding of the pathogenesis of acute myocardial infarction in that they document the presence of typical acute myocardial infarction in the absence of chronic or acute coronary arterial obstruction. They further suggest that the hearts of those dying of typical myocardial infarction show minimal or no coronary disease in approximately 7% when studied as described.
Effect of Diabetes on Renal Medullary Oxygenation During Water Diuresis
Authors: Franklin H. Epstein, Aristidis Veves, Pottumarthi V. Prasad
Journal: Diabetes Care (2002)

OBJECTIVES—To study the effect of water diuresis on renal medullary and cortical oxygenation in patients with diabetes using blood oxygenation level–dependent magnetic resonance imaging (BOLD MRI). RESEARCH DESIGN AND METHODS—Nine mild diabetic subjects (48 ±2.7 years of age, six women) and nine nondiabetic subjects of similar age and sex, all without known vascular or renal disease, were studied noninvasively by MRI before and during water diuresis. RESULTS—Water diuresis induced an increase in medullary oxygenation in control subjects, producing a decrease in R2* (apparent spin-spin relaxation time) of 1.89 ±0.27 (P &amp;lt; 0.01), but no significant change in the group of diabetic subjects. CONCLUSIONS—These findings in middle-aged diabetic subjects, which resembled those previously described in elderly subjects &amp;gt;65 years of age, suggest early impairment of adaptive vasodilatation within the renal medulla in diabetes.
Living with pulmonary hypertension: quality not just quantity
Authors: R. Condliffe
Journal: European Respiratory Journal (2011)

Pulmonary arterial hypertension (PAH) is a rare disease characterised by progressive right heart failure and premature death with a median survival prior to the availability of effective treatments of <3 yrs [1, 2]. There has been significant progress in its management over the last two decades with the introduction of three classes of targeted therapies: prostanoids, endothelin-1 receptor antagonists (ERAs) and phosphodiesterase-5 inhibitors [3]. A number of randomised controlled trials (RCTs) have demonstrated the efficacy of these drugs in terms of exercise capacity, functional class and pulmonary haemodynamics [4–11]. Observational studies have suggested improved survival when compared with historical series [12–14] and a recent meta-analysis of RCTs has confirmed a significant survival benefit associated with targeted therapies [15]. These therapies, however, have potentially significant side-effects related to continuous intravenous or subcutaneous infusion, frequent nebulisation or the requirement for close biochemical monitoring. In this context, the demonstration of therapy-related improvements in health-related quality of life (HRQoL), and not just in relatively modest improvements in exercise capacity or pulmonary haemodynamics, is of great importance to patients, prescribers and providers alike.

The majority of RCTs in PAH have assessed HRQoL as a secondary outcome using either generic tools, …
Meta-analyses of genes modulating intracellular T3 bio-availability reveal a possible role for the DIO3 gene in osteoarthritis susceptibility
Authors: I. Meulenbelt, S. D. Bos, K. Chapman, R. van der Breggen, J. J. Houwing-Duistermaat, D. Kremer, M. Kloppenburg, A. Carr, A. Tsezou, A. Gonzalez, J. Loughlin, P. E. Slagboom
Journal: Annals of the Rheumatic Diseases (2010)

To study whether common genetic variants of the genes involved in the complex regulatory mechanism determining the intracellular bio-availability of T3 influence osteoarthritis onset.In total 17 genetic variants within the genes encoding WD40-repeat/SOCS-box protein 1, ubiquitin specific protease 33, thyroid hormone receptor α, deiodinase, iodothyronine, type III (DIO3) and Indian hedgehog were measured and associated with osteoarthritis in a meta-analyses in European populations from the UK, The Netherlands, Greece and Spain containing a total of 3252 osteoarthritis cases and 2132 controls.The minor allele of the DIO3 variant rs945006 showed suggestive evidence for protective association in the overall meta-analyses, which was supported by individual osteoarthritis studies and osteoarthritis subtypes. The association appeared most significant in cases with knee and/or hip with an allelic OR of 0.81 (95% CI 0.70 to 0.930) with a nominal p value of 0.004 and a permutation-based corrected p value for multiple testing of 0.039.The findings suggest that the DIO3 gene modulates osteoarthritis disease risk; however, additional studies are necessary to replicate our findings. To elucidate the molecular mechanisms focus should be on the local adaptation to T3 availability either during the endochondral ossification process or during ageing of the articular cartilage.
Dustborne and airborne fungal propagules represent a different spectrum of fungi with differing relations to home characteristics
Authors: G. L. Chew, C. Rogers, H. A. Burge, M. L. Muilenberg, D. R. Gold
Journal: Allergy (2003)

Background: Exposure to fungi is often assessed by culturing floor dust or air samples. Our objective was to evaluate the relationships between dustborne and airborne fungi and to identify factors that modify these relationships. Methods: From November 1994 to September 1996 sequential duplicate 45‐l air samples were collected in bedrooms of 496 homes in the Boston area, using a Burkard culture plate sampler. After air sampling, bedroom floors were sampled with a vacuum cleaner that was modified to collect dust in a cellulose extraction thimble. Dust was sieved, and the fine dust was dilution‐plated onto DG‐18 media. Results: Concentrations of total culturable fungi per gram of bedroom‐floor dust were correlated weakly, but significantly, with those of indoor air ( r = 0.13, P &lt; 0.05). Concentrations of some individual taxa in the dust and indoor air were also weakly associated. Adjusting for the concentrations of fungi in outdoor air, dustborne fungal concentrations were positively associated with those in indoor air for the taxa Cladosporium and Penicillium , but not for total fungi. The indoor air fungal levels were often predicted by different covariates to those predicting fungal levels in dust. The type of housing (house or apartment) and the presence of carpeting were often predictive factors for dust fungi. In contrast, outdoor fungal levels were often predictive of the indoor air fungal levels. Conclusions: Because our data do not indicate a strong overall relationship between culturable fungi in dust and indoor air, the results from these two methods (dust and air sampling) likely represent different types of potential fungal exposures to residents. It may be essential to collect both air and dust samples, as well as information on housing characteristics, as indicators for fungal exposure.
An exploratory study of sunitinib plus paclitaxel as first-line treatment for patients with advanced breast cancer
Authors: M. Kozloff, E. Chuang, A. Starr, P.A. Gowland, P.E. Cataruozolo, M. Collier, L. Verkh, X. Huang, K.A. Kern, K. Miller
Journal: Annals of Oncology (2009)

Sunitinib has shown single-agent activity in patients with previously treated metastatic breast cancer (MBC). We investigated the safety of the combination of sunitinib and paclitaxel in an exploratory study of patients with locally advanced or MBC.Patients received oral sunitinib 25 mg/day (with escalation to 37.5 mg/day as tolerated) on a continuous daily dosing schedule and paclitaxel 90 mg/m(2) on days 1, 8, and 15 of each 28-day cycle. Study endpoints included safety (primary endpoint), pharmacokinetics, and antitumor activity.Twenty-two patients were enrolled. The most frequent adverse events (AEs) were fatigue/asthenia (77%), dysgeusia (68%), and diarrhea (64%). Grade 3 AEs included neutropenia (43%), fatigue/asthenia (27%), neuropathy (18%), and diarrhea (14%). No drug-drug interaction was observed on the basis of pharmacokinetic analysis. Of 18 patients with measurable disease at baseline, 7 (38.9%) achieved objective responses (including 2 complete and 5 partial responses). Clinical responses were observed in three of nine patients with triple-negative receptor status (estrogen receptor negative, progesterone receptor negative, and human epidermal growth factor receptor-2 negative).These data indicate that sunitinib and paclitaxel in combination are well tolerated in patients with locally advanced or MBC. No drug-drug interaction was detected and there was preliminary evidence of antitumor activity.
Website of the week: Bioterrorism
Authors: T. Jackson
Journal: BMJ (2001)

On the internet, anthrax is big business. The New York Times reported that anthrax news was creating a “marketing opportunity” on the internet and that anyone who typed “anthrax” or “cipro” into the Google.com search engine on Friday 12 October would have encountered as many as eight boxed notices with headings such as “anthrax prevention” or “Stockpile Cipro.” These offered links to online pharmacy sites where the antibiotic ciprofloxacin, used to treat inhaled anthrax, is on sale. By Tuesday, there were fewer boxed notices, but the belief in Americans' right to bear arms—even if arms simply meant antibiotics—was very much in evidence.

One of the boxed notices, with the heading “Cipro—no script required,” linked to the site of Defcon Tech, a company that “is proud to offer America survival products and information” (www.defcontech.com:8080/tech/). Current special products include “anthrax medications and survival kits”—in other words, ciprofloxacin. “Even though a large scale delivery of anthrax is difficult, our customers are choosing to play it safe,” says the site. “If terrorists strike with an epidemic size attack, nobody wants to be left without medication.” Also available is “nuclear radiation protection”—potassium iodate pills.

Appealing even more directly to the American survivalist spirit, HealthMeds.com carries a strong statement admitting it was “wrong” to say that it would scrutinise all prescriptions requesting ciprofloxacin. The company tells its customers, “Yes, you have the right to bear arms, buy gas masks and stock up on all the food and water you possibly can. You also have the right to access medications and have the absolute right to protect you and your family.”

More general anti-anthrax supplies are available at www.bioterrorismprevention.org, including gas masks, water filters, chemical suits, and “survival food tablets,” a new product which it is claimed will allow you to live for four to five months with no other foods. In design terms the site looks as if it is part of the Centers for Disease Control site. However, when I viewed it, the link to the CDC home page was defunct, and when I went to the CDC's excellent resource on bioterrorism (www.bt.cdc.gov), I could find no mention of bioterrorismprevention.org and its products.
The Effect of Megestrol Acetate on Growth of HepG2 Cells <b> <i>In vitro</i> </b> and <b> <i>In vivo</i> </b>
Authors: Kai Zhang, Pierce K. H. Chow
Journal: Clinical Cancer Research (2004)

Abstract Purpose: Hepatocellular carcinoma (HCC) is generally considered as a sex hormone-dependent tumor, and hormonal therapy has been proposed as a strategy for the treatment of HCC. The aim of the study is to investigate the effect of megestrol acetate, a synthetic progesteronal agent, on growth of HepG2 cells in vitro and in vivo. Experimental Design: Cell growth in vitro was assessed by a colormetric method, and cell growth in vivo was assessed by tumor volumetrics. Results: Megestrol acetate was shown to inhibit the growth of HepG2 cells in vitro in dose- and time-dependent manners with an IC 50 of 260 μm (24-h incubation). The growth of HepG2 cell-transplanted tumors in nude mice was also inhibited by i.p. injection of megestrol acetate (10 mg/kg/day). The tumor volumes of the megestrol acetate-treated group regressed to 59% of controls by week 6 and to 41% of controls by week 13. Apoptosis following G1 arrest was observed in megestrol acetate-treated cells and may be a mechanism through which megestrol acetate inhibits HepG2 cells. Megestrol acetate was also demonstrated to have a beneficial effect on the weight gain of tumor-bearing nude mice, and the mean weight of the megestrol acetate-treated animals was higher than that of controls from week 4 of the treatment period, and the differences were statistically significant in week 5 and 6 (P &amp;lt; 0.05, compared with controls). No significant survival advantage was, however, demonstrated in the treatment group. Conclusions: This study showed that megestrol acetate inhibited the growth of HepG2 cells grown in vitro and in vivo. These data provide useful information for clinical study of megestrol acetate for the treatment of HCC.