tbuckley/cabot-search huggingface dataset:
Chemotactic effect of joint effusions.
Authors: B Stojan, J F Borel, G Loewi
Journal: Annals of the Rheumatic Diseases (1974)

This paper reports the incidence of chemotactic activity of joint effusions obtained from several diseases involving joints.Ward and Zvaifler (1971) found that such activity was present in the majority of effusions in rheumatoid arthritis, but also in some cases of other nonspecified forms of inflammatory arthritis, gout, and osteoarthritis.These authors used rabbit neutrophil polymorphs to assess chemotaxis.We have repeated their observations using human polymorphs from both autologous and homologous sources.This work was conducted independently in two centres, using different methods.The results, which proved to be similar, are reported separately below. MethodsJoint effusions were obtained from patients as detailed in Tables I andII.Diagnosis of rheumatoid arthritis (RA) was made in accordance with A.R.A. criteria, and of juvenile rheumatoid arthritis following the criteria of Ansell and Bywaters (1959).Other diseases were diagnosed according to the usually accepted criteria.Fluids were mixed with 15 units heparin/ml.No hyaluronidase was used for the Basle cases; it was used in a few of the Taplow cases, when the viscosity of fluids was high.The fluids were centrifuged at 1,800 g for 20 mins, to obtain clear supernatants.Some fluids were used fresh, others after storage at -20°C.Tests were conducted with joint fluids undiluted, or diluted 1:1 with Gey's medium.White blood cells, the source of polymorphs, were obtained from heparinized (10 units/ml) human venous blood.Sedimentation was achieved by adding 1 ml dextran 110 (Fisons) to 10 ml blood, and sedimenting for 1 hour at room temperature.For the Taplow work, Plasmagel (Roger Bellon) was used instead.After centri- fugation and washing in Gey's medium, the cells were suspended in Gey's containing 2 % human serum albumin to give a leucocyte suspension of 1-1 5 x 106 polymorphs/ ml.For the method used at Taplow, a concentration of 3-4 x 1061/m was used. CHEMOTAXISThis was assayed by a modified Boyden chamber technique (by J. F. B. and B. S.) (Boyden, 1962; Keller, Borel, Wilkinson, Hess, and Cottier, 1972) and by the method of Maroni, Symon, and Wilkinson (1972) (by G. L.).For the Boyden chamber technique, double filters were used.* Figures in the 3 columns denote average number of cells counted per high-power microscopical field.Controls (1): Gey's solution 2% HSA; Controls (2): supernatants from Esch. coli culture, 10% dilution in Gey's solution; synovial fluids: used undiluted.t Culture supernatant diluted 20 x, resulting in low value.: Positive test.NT: not tested.Rheumatoid factor (sero +, sero -) was measured by latex test.
Examining the Other Kidney in Nephrectomy.
Authors: J. F. Baldwin
Journal: JAMA (1907)

Columbus, Ohio, June 17, 1907. <h3>To the Editor:</h3> —In your issue of June 1 Dr. Edebohls advised exploration and decapsulation, through an incision in the loin, of the other kidney before making a nephrectomy. The advice always to be sure of the other kidney can not be too strongly emphasized, but in my own work I have been in the habit of exploring the other kidney through the incision made for the nephrectomy. One can readily enter the peritoneal cavity in front of the colon, and with the gloved hand and arm palpate carefully the other kidney, and thus determine in a general way its condition. After withdrawing the hand the opening in the peritoneum is closed with catgut, and the nephrectomy proceeded with in the usual way. This gives but one wound, takes less time, and is practically as satisfactory as the method suggested by Dr. Edebohls, except that
P-cadherin counteracts myosin II-B function: implications in melanoma progression
Authors: Koen Jacobs, Mireille Van Gele, Ramses Forsyth, Lieve Brochez, Barbara Vanhoecke, Olivier De Wever, Marc Bracke
Journal: Molecular Cancer (2010)

Abstract Background Malignant transformation of melanocytes is frequently attended by a switch in cadherin expression profile as shown for E- and N-cadherin. For P-cadherin, downregulation in metastasizing melanoma has been demonstrated, and over-expression of P-cadherin in melanoma cell lines has been shown to inhibit invasion. The strong invasive and metastatic nature of cutaneous melanoma implies a deregulated interplay between intercellular adhesion and migration-related molecules Results In this study we performed a microarray analysis to compare the mRNA expression profile of an invasive BLM melanoma cell line (BLM LIE) and the non-invasive P-cadherin over-expression variant (BLM P-cad). Results indicate that nonmuscle myosin II-B is downregulated in BLM P-cad. Moreover, myosin II-B plays a major role in melanoma migration and invasiveness by retracting the tail during the migratory cycle, as shown by the localization of myosin II-B stress fibers relative to Golgi and the higher levels of phosphorylated myosin light chain. Analysis of P-cadherin and myosin II-B in nodular melanoma sections and in a panel of melanoma cell lines further confirmed that there is an inverse relationship between both molecules. Conclusions Therefore, we conclude that P-cadherin counteracts the expression and function of myosin II-B, resulting in the suppression of the invasive and migratory behaviour of BLM melanoma cells
People at risk of coronary heart disease should not be denied treatment with effective drugs for purely financial reasons
Authors: T M Reynolds, A S Wierzbicki, M A Crook, N E Capps
Journal: BMJ (1998)

EDITOR—As soon as effective treatments for coronary heart disease—which causes 30% of deaths in the United Kingdom—became available, evidence based medicine and finance clashed. The Standing Medical Advisory Committee attempted to impose the Sheffield risk tables1 and was condemned for its simplistic guidelines and high threshold for treatment.2 A report on cholesterol and heart disease by the NHS Centre for Reviews and Dissemination now seeks to reduce expenditure on statins by focusing clinical effort on modification of lifestyle and treatment for mild hypertension. …
25-hydroxyvitamin D<sub>3</sub>suppresses hepatitis C virus production
Authors: Takuya Matsumura, Takanobu Kato, Nao Sugiyama, Megumi Tasaka-Fujita, Asako Murayama, Takahiro Masaki, Takaji Wakita, Michio Imawari
Journal: Hepatology (2012)

Because the current interferon (IFN)-based treatment for hepatitis C virus (HCV) infection has a therapeutic limitation and side effects, a more efficient therapeutic strategy is desired. Recent studies show that supplementation of vitamin D significantly improves sustained viral response via IFN-based therapy. However, mechanisms and an active molecular form of vitamin D for its anti-HCV effects have not been fully clarified. To address these questions, we infected HuH-7 cells with cell culture-generated HCV in the presence or absence of vitamin D(3) or its metabolites. To our surprise, 25-hydroxyvitamin D(3) [25(OH)D(3) ], but not vitamin D(3) or 1,25-dihydroxyvitamin D(3) , reduced the extra- and intracellular levels of HCV core antigen in a concentration-dependent manner. Single-cycle virus production assay with a CD81-negative cell line reveals that the inhibitory effect of 25(OH)D(3) is at the level of infectious virus assembly but not entry or replication. Long-term 25(OH)D(3) treatment generates a HCV mutant with acquired resistance to 25(OH)D(3) , and this mutation resulting in a N1279Y substitution in the nonstructural region 3 helicase domain is responsible for the resistance.25(OH)D(3) is a novel anti-HCV agent that targets an infectious viral particle assembly step. This finding provides insight into the improved efficacy of anti-HCV treatment via the combination of vitamin D(3) and IFN. Our results also suggest that 25(OH)D(3) , not vitamin D(3) , is a better therapeutic option in patients with hepatic dysfunction and reduced enzymatic activity for generation of 25(OH)D(3) .
THE USE OF PITUITARY SOLUTION
Authors: Arthur Stein
Journal: JAMA (1930)

To the Editor:  —I would like to take issue with recent contributions to medical literature which have commented adversely and, in my opinion, without sufficient justification on the use of solution of pituitary for induction of labor. I refer especially to Dr. A. M. Mendenhall, whose article was featured in your issue of April 20, 1929. More recently Dr. Nicholas Temesvary ( Am. J. Obst. & Gynec. , February, 1930) in presenting his favorable impressions from experimentation with thymophysin has dismissed the use of pituitary extract with the rather sweeping statement that it can be given only during the expulsion period or at the utmost with a disappearing os uteri, as it often causes tetanic contractions of the uterus, which may be harmful to the mother and the fetus during the dilatation period.  If Dr. Mendenhall had endeavored to impress his readers with the necessity of thorough knowledge of technic in use
Changing mortality from ischaemic heart disease in Great Britain 1968-76.
Authors: C du V Florey, R J Melia, S C Darby
Journal: BMJ (1978)

The decline in death rates from ischaemic heart disease (IHD) (ICD 410-413) in the United States is now well documented. Over-the period 1963-75 the drop in age-specific mortality varied from 27 2O for those aged 35-44 to 19-30o for the over-85s.1 Concurrent with these changes have been reductions in the consumption of tobacco products, milk and cream, butter, eggs, and animal fats and oils and an increase in the use of vegetable fats and oils. In England and Wales no similar encouraging change in IHD mortality has been described. In the Royal College of Physicians' report2 annual death rates for IHD in men aged 35-44, 45-54, and 55-64 showed a pronounced increase from the period 1950-2 to 1973. There was, on the other hand, little change in the rates for women. Similar findings were presented for the Republic of Ireland, Northern Ireland, and Scotland, the latter two having substantially higher rates than England and Wales. A detailed analysis of mortality from heart disease in England and Wales for the years 1950-73'3 4has confirmed the general upward trend for men even after allowing for the possibility of an iatrogenic transfer of diagnosis from the rubrics for hypertension and myocardial insufficiency to that of IHD. The mortality trends for women are less clear. Clayton et al3 concluded that no change in death rates took place during the period 1950-73 in women aged 50 and over, but that there was a consistent increase for young women. The combination of IHD with other rubrics in this analysis has been questioned by Wald and Mann,; who believe that there was no justification for combining deaths from hypertension with those of IHD. The trends for IHD alone indicated an increase for all women up to age 64. We present mortality data for 1968-76 for England and Wales and for Scotland that suggest that IHD death rates for men stabilised in about 1972 and since then have started to decline. No similar decline was found for mortality in women.
Drug Management of Obesity — Efficacy versus Safety
Authors: Arne Astrup
Journal: New England Journal of Medicine (2010)

The history of pharmacologic treatment of obesity is characterized by repetition: most drugs that have achieved regulatory approval and reached the markets have subsequently been withdrawn owing to postmarketing discovery of serious adverse effects. In 2007, the cannabinoid-receptor antagonist rimonabant was not approved by the Food and Drug Administration (FDA) and was withdrawn from the market in Europe because of an increased risk of depression, anxiety, and suicidal ideation1; the development program for several compounds of the same class that were in phase 3 studies had to be terminated. In January of this year, the European Medicine Agency's Committee . . .
Seasonal distribution in conceptions achieved by artificial insemination by donor
Authors: M J Mayaux, A Spira
Journal: BMJ (1989)

patients with confirmed acute myocardial infarc- tion were admitted to the seven bedded coronary care unit of Leicester Royal Infirmary within six hours after the onset of symptoms.Thrombolytic treatment of that number of patients would cost £29 000 with streptokinase compared with £344 000 with plasminogen activator for the drugs alone, according to the manufacturers' published prices.Streptokinase (plus aspirin) will remain the best treatment until evidence from direct comparative trials shows that an alternative thrombolytic agent can result in a lower mortality or until the price of an equally effective drug becomes competitive.
Alteration of Epigenetic Profile in Human Hepatocellular Carcinoma and Its Clinical Implications
Authors: Naoshi Nishida, Masatoshi Kudo
Journal: Liver Cancer (2014)

Hepatocellular carcinoma (HCC) is a common cancer worldwide and develops against a background of chronic liver damage. A variety of HCC-related genes are known to be altered by genetic and epigenetic mechanisms. Therefore, information regarding alteration of the genetic and epigenetic profiles in HCC is essential for understanding the biology of this type of tumor. Methylation at CpG sites in gene promoters is known to affect the transcription of the corresponding genes. Abnormal regional hypermethylation is observed in the 5′ region of several tumor suppressor genes (TSGs) in HCC, and this hypermethylation may promote carcinogenesis through the transcriptional inactivation of downstream TSGs. The DNA damage induced by oxidation is a trigger of abnormal DNA methylation and inactivation of TSGs through recruitment of the polycomb repressive complex to the promoter sequence. Thus, oxidative stress may be responsible for the emergence of HCC from chronic hepatitis and liver cirrhosis through the epigenetic alteration of TSGs. There have been several attempts to apply epigenetic information to the diagnosis and treatment of HCC. The predictive value of selected methylation events on survival in HCC patients has been reported, and the methylation profile of background liver could be associated with recurrence-free survival of HCC patients who have undergone hepatectomy. Another study detected methylated DNA from HCC cells in serum, and the circulating tumor DNA was regarded as a potential tumor marker. In addition, several trials of HCC therapy have targeted the epigenetic machinery and were based upon comprehensive analyses of DNA methylation of this type of tumor. Here, we present an overview of research regarding DNA methylation status in human HCC and describe the clinical application of epigenetic information to HCC.
Effect of vaccination on severity and dissemination of whooping cough.
Authors: P R Grob, M J Crowder, J F Robbins
Journal: BMJ (1981)

A study was undertaken in general practice to clarify those factors, especially vaccinations, that influence the clinical picture and infectivity of whooping cough in the community. Although the range of the disease encountered was fairly mild, its duration was notable (mean +/- SD 50.9 +/- 32.1 days). By using multiway contingency table analysis it was found that in the more severe cases of whooping cough vaccination significantly shortened the illness (p less than 0.005) and reduced the number of coughing spasms (p less than 0.025). The protective effect of the vaccine was most notable in modifying infectivity within the family: 19% of vaccinated family contacts of index patients in whom the disease had been confirmed bacteriologically developed the disease when exposed to it compared with 72% of non-vaccinated contacts (p less than 0.001). These results show that whooping cough vaccination modifies the clinical illness and offers a worthwhile degree of protection to children exposed to the disease.
P14 Pneumonia: 30 Months of Advancing Quality in North West England: Abstract P14 Table 1
Authors: MA Woodhead, L Kitchen, G Morrow
Journal: Thorax (2012)

<h3></h3> As part of an initiative to improve the quality of care within the North West Strategic Health Authority, five ‘quality markers’ (QMs) were measured in all adult admissions with pneumonia in all 23 Acute Trusts in the North West Region. Results for discharges for 30 months from October 2008 are presented. Data reporting was changed to match the financial year in 2009 so cohorts from October 2008-September 2009, October 2009-March 2010 and April 2010-March 2011 are presented. Only adults who fulfilled a prescribed definition of ‘pneumonia’ were included. QMs were taken from a USA initiative and adapted for UK use. Patient identification was based on clinical coding. Data was recorded in each individual Trust and centrally collated. Data on 31,972 pneumonia episodes were included (11,127, 6,683, 14,162 in each time period respectively). Mean results of % compliance for each variable for each Trust, together with standard deviation as a measure of variability across hospital sites, are presented in the Table for each cohort. Initial compliance was worst for administration of smoking cessation advice and best for oxygenation assessment. While variability between hospitals was least for oxygenation it was greatest for the performance of blood cultures prior to antibiotic administration. Over the 3 cohorts overall compliance with QM assessment steadily improved for all QMs and variability between Trusts declined for all but smoking cessation advice. <h3>Conclusions</h3> The Advancing Quality Programme has resulted in improved quality of pneumonia care as assessed by both the improvement in overall compliance and the reduction in inter-hospital variability.
Neuropsychiatric complications related to use of prazosin in patients with renal failure.
Authors: D K Chin, A K Ho, C Y Tse
Journal: BMJ (1986)

That the efferent limb of the "clubbing reflex" may be humoral is suggested by observations of hormonal factors being associated with clubbing.Patients with bronchial carcinoma and hypertrophic pulmonary osteoarthropathy have been reported to have raised concentrations ofgrowth hormone.3Clubbing has also been described in association with a case of thyroid carcinoma and primary hyperparathyroidism.4 Lam et al reported two cases (in brothers) with pachydermatoperiostosis, hypertrophic gastropathy, and complicated duodenal ulcers.5In these cases the serum concentrations of gastrin were normal but concentrations of pepsinogen 1 and 2 were raised.The clubbing associated with the Zollinger-Ellison syndrome in our patient, which regressed after resection of the tumour, was probably due to some substance produced by the tumour.Gastrin itselfwas unlikely to be the substance, as vagotomy, which may abolish clubbing, is often associated with raised serum concentrations of gastrin.Moreover, tumours such as gastrinomas, which are from the APUD cell series, are known to secrete many peptides, only some ofwhich have been characterised.1 Hal GH, Laidlaw CD'A.Further eerimental evice implicating reduced ferritin as a cause of digial clubbing.CiSci 1963,24:121-6.
French plan to bail out social security system
Authors: A. Dorozynski
Journal: BMJ (1997)

The French government has introduced sweeping reforms to rescue the ailing social security system and its national health insurance plan.

The new proposal is for middle and upper income families to pay higher contributions to the system and for additional revenue to be generated by taxing savings accounts, life insurance, and capital gains.

At present contributions are based on salaries, with employees' contributions set at 5.5% of gross salary; …
Effects of 5 years of treatment with lasofoxifene on incidence of breast cancer in older women.
Authors: AZ LaCroix, SR Cummings, P Delmas, R Eastell, K Ensrud, DM Reid, S Vukicevic, RA Armstrong, J Thompson, D Thompson, K Wolter, C Allred, P Goss, KC Osborne, TJ Powles
Journal: Cancer Research (2009)

Abstract Abstract #11 The Postmenopausal Evaluation and Risk-reduction with Lasofoxifene (PEARL) Trial evaluated the effects of 5 years of a new potent SERM on the incidence of estrogen receptor positive (ER+) breast cancer (BC) (co-primary endpoints, invasive alone and invasive plus ductal carcinoma in situ [DCIS] together). 8556 women ages 5980 with femoral neck or spine T-score ≤ –2.5 and &amp;gt; –4.5 were enrolled in 32 countries. Women were randomly assigned to receive 0.25 mg/d or 0.5 mg/d of lasofoxifene (LASO), or placebo (PBO). BC events were ascertained through annual clinical breast exam and mammographic screening and adjudicated by physician oncologists and a BC pathologist blinded to treatment assignment. 77% of women completed 5 years of follow-up and 62–64% remained on study medication until planned trial closure. ITT analyses were conducted using Cox Proportional Hazards models. The protocol-defined primary analysis for all ER+ BCs compared each of the LASO groups to PBO. In the PBO group, 21 women developed invasive or non-invasive ER+ BC (17.3/10,000 person-years (P-Y)) compared to 10 in the LASO 0.25 mg/d group (9.0/10,000 P-Y; HR=0.52, 95%CI 0.25–1.08) and 5 in the 0.5 mg/d LASO group (3.3/10,000 P-Y; HR=0.19, 95% CI 0.07–0.56). For all invasive BCs (ER+ve and ve), 20 women in the PBO group were affected (16.4/10,000) compared to 16 in the LASO 0.25 mg/d group (13.2/10,000 P-Y; HR=0.79, 95%CI 0.41–1.52) and 3 in the 0.5 mg/d LASO group (2.5/10,000 P-Y; HR=0.15, 95% CI 0.04–0.50). For total BC, 24 women in the PBO group were affected (19.8/10,000 P-Y) compared to 20 in the LASO 0.25 mg/d group (16.4/10,000 P-Y; HR=0.82, 95%CI 0.45–1.49) and 5 in the 0.5 mg/d LASO group (4.1/10,000 P-Y; HR=0.21, 95% CI 0.08–0.55). Too few cases of DCIS occurred to determine effects of LASO on noninvasive breast tumors. No significant differences among treatment groups were observed for breast density. LASO also reduced the incidence of vertebral (primary at 3 years) and nonvertebral clinical fractures (co-primary at 5-years). LASO increased risk of venous thromboembolic events, but not stroke, endometrial cancer or endometrial hyperplasia and decreased risk of major coronary events at 0.5 mg/d. Endometrial hypertrophy, uterine polyps, and fibroids were more common with LASO while hypertension and hyperlipidemia was less frequent compared to PBO. We conclude that LASO reduces the incidence of ER+ BC and appears to have a favorable benefit-risk profile for prevention of clinical fractures in postmenopausal women with osteoporosis. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 11.